Infectious Diseases

This transcript has been edited for clarity.

It was only 3 years ago when we called the pathogen we now refer to as the coronavirus “nCOV-19.” It was, in many ways, more descriptive than what we have today. The little “n” there stood for “novel” — and it was really that little “n” that caused us all the trouble.

You see, coronaviruses themselves were not really new to us. Understudied, perhaps, but with four strains running around the globe at any time giving rise to the common cold, these were viruses our bodies understood.

But the coronavirus discovered in 2019 was novel — not just to the world, but to our own immune systems. It was different enough from its circulating relatives that our immune memory cells failed to recognize it. Instead of acting like a cold, it acted like nothing we had seen before, at least in our lifetime. The story of the pandemic is very much a bildungsroman of our immune systems — a story of how our immunity grew up.

The difference between the start of 2020 and now, when infections with the coronavirus remain common but not as deadly, can be measured in terms of immune education. Some of our immune systems were educated by infection, some by vaccination, and many by both.

When the first vaccines emerged in December 2020, the opportunity to educate our immune systems was still huge. Though, at the time, an estimated 20 million had been infected in the US and 350,000 had died, there was a large population that remained immunologically naive. I was one of them.

If 2020 into early 2021 was the era of immune education, the postvaccine period was the era of the variant. From one COVID strain to two, to five, to innumerable, our immune memory — trained on a specific version of the virus or its spike protein — became imperfect again. Not naive; these variants were not “novel” in the way COVID-19 was novel, but they were different. And different enough to cause infection.

Following the playbook of another virus that loves to come dressed up in different outfits, the flu virus, we find ourselves in the booster era — a world where yearly doses of a vaccine, ideally matched to the variants circulating when the vaccine is given, are the recommendation if not the norm.

But questions remain about the vaccination program, particularly around who should get it. And two populations with big question marks over their heads are (1) people who have already been infected and (2) kids, because their risk for bad outcomes is so much lower.

This week, we finally have some evidence that can shed light on these questions. The study under the spotlight is this one, appearing in JAMA, which tries to analyze the ability of the bivalent vaccine — that’s the second one to come out, around September  2022 — to protect kids from COVID-19.

Now, right off the bat, this was not a randomized trial. The studies that established the viability of the mRNA vaccine platform were; they happened before the vaccine was authorized. But trials of the bivalent vaccine were mostly limited to proving immune response, not protection from disease.

Nevertheless, with some good observational methods and some statistics, we can try to tease out whether bivalent vaccines in kids worked.

The study combines three prospective cohort studies. The details are in the paper, but what you need to know is that the special sauce of these studies was that the kids were tested for COVID-19 on a weekly basis, whether they had symptoms or not. This is critical because asymptomatic infections can transmit COVID-19.

Let’s do the variables of interest. First and foremost, the bivalent vaccine. Some of these kids got the bivalent vaccine, some didn’t. Other key variables include prior vaccination with the monovalent vaccine. Some had been vaccinated with the monovalent vaccine before, some hadn’t. And, of course, prior infection. Some had been infected before (based on either nasal swabs or blood tests).

Let’s focus first on the primary exposure of interest: getting that bivalent vaccine. Again, this was not randomly assigned; kids who got the bivalent vaccine were different from those who did not. In general, they lived in smaller households, they were more likely to be White, less likely to have had a prior COVID infection, and quite a bit more likely to have at least one chronic condition.

JAMA

JAMA

JAMA

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

It was only 3 years ago when we called the pathogen we now refer to as the coronavirus “nCOV-19.” It was, in many ways, more descriptive than what we have today. The little “n” there stood for “novel” — and it was really that little “n” that caused us all the trouble.

You see, coronaviruses themselves were not really new to us. Understudied, perhaps, but with four strains running around the globe at any time giving rise to the common cold, these were viruses our bodies understood.

But the coronavirus discovered in 2019 was novel — not just to the world, but to our own immune systems. It was different enough from its circulating relatives that our immune memory cells failed to recognize it. Instead of acting like a cold, it acted like nothing we had seen before, at least in our lifetime. The story of the pandemic is very much a bildungsroman of our immune systems — a story of how our immunity grew up.

The difference between the start of 2020 and now, when infections with the coronavirus remain common but not as deadly, can be measured in terms of immune education. Some of our immune systems were educated by infection, some by vaccination, and many by both.

When the first vaccines emerged in December 2020, the opportunity to educate our immune systems was still huge. Though, at the time, an estimated 20 million had been infected in the US and 350,000 had died, there was a large population that remained immunologically naive. I was one of them.

If 2020 into early 2021 was the era of immune education, the postvaccine period was the era of the variant. From one COVID strain to two, to five, to innumerable, our immune memory — trained on a specific version of the virus or its spike protein — became imperfect again. Not naive; these variants were not “novel” in the way COVID-19 was novel, but they were different. And different enough to cause infection.

Following the playbook of another virus that loves to come dressed up in different outfits, the flu virus, we find ourselves in the booster era — a world where yearly doses of a vaccine, ideally matched to the variants circulating when the vaccine is given, are the recommendation if not the norm.

But questions remain about the vaccination program, particularly around who should get it. And two populations with big question marks over their heads are (1) people who have already been infected and (2) kids, because their risk for bad outcomes is so much lower.

This week, we finally have some evidence that can shed light on these questions. The study under the spotlight is this one, appearing in JAMA, which tries to analyze the ability of the bivalent vaccine — that’s the second one to come out, around September  2022 — to protect kids from COVID-19.

Now, right off the bat, this was not a randomized trial. The studies that established the viability of the mRNA vaccine platform were; they happened before the vaccine was authorized. But trials of the bivalent vaccine were mostly limited to proving immune response, not protection from disease.

Nevertheless, with some good observational methods and some statistics, we can try to tease out whether bivalent vaccines in kids worked.

The study combines three prospective cohort studies. The details are in the paper, but what you need to know is that the special sauce of these studies was that the kids were tested for COVID-19 on a weekly basis, whether they had symptoms or not. This is critical because asymptomatic infections can transmit COVID-19.

Let’s do the variables of interest. First and foremost, the bivalent vaccine. Some of these kids got the bivalent vaccine, some didn’t. Other key variables include prior vaccination with the monovalent vaccine. Some had been vaccinated with the monovalent vaccine before, some hadn’t. And, of course, prior infection. Some had been infected before (based on either nasal swabs or blood tests).

Let’s focus first on the primary exposure of interest: getting that bivalent vaccine. Again, this was not randomly assigned; kids who got the bivalent vaccine were different from those who did not. In general, they lived in smaller households, they were more likely to be White, less likely to have had a prior COVID infection, and quite a bit more likely to have at least one chronic condition.

JAMA

JAMA

JAMA

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

It was only 3 years ago when we called the pathogen we now refer to as the coronavirus “nCOV-19.” It was, in many ways, more descriptive than what we have today. The little “n” there stood for “novel” — and it was really that little “n” that caused us all the trouble.

You see, coronaviruses themselves were not really new to us. Understudied, perhaps, but with four strains running around the globe at any time giving rise to the common cold, these were viruses our bodies understood.

But the coronavirus discovered in 2019 was novel — not just to the world, but to our own immune systems. It was different enough from its circulating relatives that our immune memory cells failed to recognize it. Instead of acting like a cold, it acted like nothing we had seen before, at least in our lifetime. The story of the pandemic is very much a bildungsroman of our immune systems — a story of how our immunity grew up.

The difference between the start of 2020 and now, when infections with the coronavirus remain common but not as deadly, can be measured in terms of immune education. Some of our immune systems were educated by infection, some by vaccination, and many by both.

When the first vaccines emerged in December 2020, the opportunity to educate our immune systems was still huge. Though, at the time, an estimated 20 million had been infected in the US and 350,000 had died, there was a large population that remained immunologically naive. I was one of them.

If 2020 into early 2021 was the era of immune education, the postvaccine period was the era of the variant. From one COVID strain to two, to five, to innumerable, our immune memory — trained on a specific version of the virus or its spike protein — became imperfect again. Not naive; these variants were not “novel” in the way COVID-19 was novel, but they were different. And different enough to cause infection.

Following the playbook of another virus that loves to come dressed up in different outfits, the flu virus, we find ourselves in the booster era — a world where yearly doses of a vaccine, ideally matched to the variants circulating when the vaccine is given, are the recommendation if not the norm.

But questions remain about the vaccination program, particularly around who should get it. And two populations with big question marks over their heads are (1) people who have already been infected and (2) kids, because their risk for bad outcomes is so much lower.

This week, we finally have some evidence that can shed light on these questions. The study under the spotlight is this one, appearing in JAMA, which tries to analyze the ability of the bivalent vaccine — that’s the second one to come out, around September  2022 — to protect kids from COVID-19.

Now, right off the bat, this was not a randomized trial. The studies that established the viability of the mRNA vaccine platform were; they happened before the vaccine was authorized. But trials of the bivalent vaccine were mostly limited to proving immune response, not protection from disease.

Nevertheless, with some good observational methods and some statistics, we can try to tease out whether bivalent vaccines in kids worked.

The study combines three prospective cohort studies. The details are in the paper, but what you need to know is that the special sauce of these studies was that the kids were tested for COVID-19 on a weekly basis, whether they had symptoms or not. This is critical because asymptomatic infections can transmit COVID-19.

Let’s do the variables of interest. First and foremost, the bivalent vaccine. Some of these kids got the bivalent vaccine, some didn’t. Other key variables include prior vaccination with the monovalent vaccine. Some had been vaccinated with the monovalent vaccine before, some hadn’t. And, of course, prior infection. Some had been infected before (based on either nasal swabs or blood tests).

Let’s focus first on the primary exposure of interest: getting that bivalent vaccine. Again, this was not randomly assigned; kids who got the bivalent vaccine were different from those who did not. In general, they lived in smaller households, they were more likely to be White, less likely to have had a prior COVID infection, and quite a bit more likely to have at least one chronic condition.

JAMA

JAMA

JAMA

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

New evidence suggests that SARS-CoV-2 infection can lead to the rapid development of achalasia, a rare esophageal motility disorder.

METHODOLOGY:

• The etiology of achalasia is unclear. Studies have suggested an immune reaction to viral infections, including SARS-CoV-2, as a potential cause.
• Researchers studied four adults who developed achalasia within 5 months of SARS-CoV-2 infection (group 1), six with longstanding achalasia predating SARS-CoV-2 infection (group 2), and two with longstanding achalasia with no known SARS-CoV-2 infection (group 3).
• They tested for the presence of SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, as well as inflammatory markers, in esophageal muscle tissue isolated from the participants.

TAKEAWAY:

• Group 1 patients (confirmed or suspected post–COVID-19 achalasia) had the highest levels of the N protein in all four cases and higher levels of the S protein in the two confirmed cases. No N or S protein was detected in group 3.
• The presence of mRNA for SARS-CoV-2 N protein correlated with a significant increase in the inflammatory markers of NOD-like receptor family pyrin domain-containing 3 and tumor necrosis factor. There were no differences in interleukin 18 in groups 1 and 2.
• The S protein was detected in all muscle tissue samples from group 1. It was also detected in some (but not all) samples from group 2 and to a much lesser degree. The presence of S protein was irrespective of the SARS-CoV-2 vaccination status.

IN PRACTICE:

“Our findings not only show the continued presence of SARS-CoV-2 proteins in esophageal muscle tissue isolated from subjects with achalasia post infection, but they further correlate this with the presence of a sustained inflammatory response,” the authors wrote.

SOURCE:

The study, with first author Salih Samo, MD, MS, Division of Gastroenterology, Hepatology, and Motility, University of Kansas School of Medicine, Kansas City, Kansas, was published online on January 24, 2024, in the American Journal of Gastroenterology.

LIMITATIONS:

The sample size was small, and it was not known which SARS-CoV-2 variant each patient had. The study cannot definitively confirm that SARS-CoV-2 is causative for achalasia.

DISCLOSURES:

The study had no specific funding. Samo reported relationships with Castle Biosciences, Sanofi, Evoke, and EndoGastric Solutions.

A version of this article appeared on Medscape.com.

TOPLINE:

New evidence suggests that SARS-CoV-2 infection can lead to the rapid development of achalasia, a rare esophageal motility disorder.

METHODOLOGY:

• The etiology of achalasia is unclear. Studies have suggested an immune reaction to viral infections, including SARS-CoV-2, as a potential cause.
• Researchers studied four adults who developed achalasia within 5 months of SARS-CoV-2 infection (group 1), six with longstanding achalasia predating SARS-CoV-2 infection (group 2), and two with longstanding achalasia with no known SARS-CoV-2 infection (group 3).
• They tested for the presence of SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, as well as inflammatory markers, in esophageal muscle tissue isolated from the participants.

TAKEAWAY:

• Group 1 patients (confirmed or suspected post–COVID-19 achalasia) had the highest levels of the N protein in all four cases and higher levels of the S protein in the two confirmed cases. No N or S protein was detected in group 3.
• The presence of mRNA for SARS-CoV-2 N protein correlated with a significant increase in the inflammatory markers of NOD-like receptor family pyrin domain-containing 3 and tumor necrosis factor. There were no differences in interleukin 18 in groups 1 and 2.
• The S protein was detected in all muscle tissue samples from group 1. It was also detected in some (but not all) samples from group 2 and to a much lesser degree. The presence of S protein was irrespective of the SARS-CoV-2 vaccination status.

IN PRACTICE:

“Our findings not only show the continued presence of SARS-CoV-2 proteins in esophageal muscle tissue isolated from subjects with achalasia post infection, but they further correlate this with the presence of a sustained inflammatory response,” the authors wrote.

SOURCE:

The study, with first author Salih Samo, MD, MS, Division of Gastroenterology, Hepatology, and Motility, University of Kansas School of Medicine, Kansas City, Kansas, was published online on January 24, 2024, in the American Journal of Gastroenterology.

LIMITATIONS:

The sample size was small, and it was not known which SARS-CoV-2 variant each patient had. The study cannot definitively confirm that SARS-CoV-2 is causative for achalasia.

DISCLOSURES:

The study had no specific funding. Samo reported relationships with Castle Biosciences, Sanofi, Evoke, and EndoGastric Solutions.

A version of this article appeared on Medscape.com.

TOPLINE:

New evidence suggests that SARS-CoV-2 infection can lead to the rapid development of achalasia, a rare esophageal motility disorder.

METHODOLOGY:

• The etiology of achalasia is unclear. Studies have suggested an immune reaction to viral infections, including SARS-CoV-2, as a potential cause.
• Researchers studied four adults who developed achalasia within 5 months of SARS-CoV-2 infection (group 1), six with longstanding achalasia predating SARS-CoV-2 infection (group 2), and two with longstanding achalasia with no known SARS-CoV-2 infection (group 3).
• They tested for the presence of SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, as well as inflammatory markers, in esophageal muscle tissue isolated from the participants.

TAKEAWAY:

• Group 1 patients (confirmed or suspected post–COVID-19 achalasia) had the highest levels of the N protein in all four cases and higher levels of the S protein in the two confirmed cases. No N or S protein was detected in group 3.
• The presence of mRNA for SARS-CoV-2 N protein correlated with a significant increase in the inflammatory markers of NOD-like receptor family pyrin domain-containing 3 and tumor necrosis factor. There were no differences in interleukin 18 in groups 1 and 2.
• The S protein was detected in all muscle tissue samples from group 1. It was also detected in some (but not all) samples from group 2 and to a much lesser degree. The presence of S protein was irrespective of the SARS-CoV-2 vaccination status.

IN PRACTICE:

“Our findings not only show the continued presence of SARS-CoV-2 proteins in esophageal muscle tissue isolated from subjects with achalasia post infection, but they further correlate this with the presence of a sustained inflammatory response,” the authors wrote.

SOURCE:

The study, with first author Salih Samo, MD, MS, Division of Gastroenterology, Hepatology, and Motility, University of Kansas School of Medicine, Kansas City, Kansas, was published online on January 24, 2024, in the American Journal of Gastroenterology.

LIMITATIONS:

The sample size was small, and it was not known which SARS-CoV-2 variant each patient had. The study cannot definitively confirm that SARS-CoV-2 is causative for achalasia.

DISCLOSURES:

The study had no specific funding. Samo reported relationships with Castle Biosciences, Sanofi, Evoke, and EndoGastric Solutions.

A version of this article appeared on Medscape.com.

To the Editor:

Kaposi sarcoma (KS) is a rare angioproliferative disorder associated with human herpesvirus 8 (HHV-8) infection.¹ There are 4 main recognized epidemiologic forms of KS: classic, endemic, epidemic, and iatrogenic (Table). Nonepidemic KS is a recently described rare fifth type of KS that occurs in a subset of patients who do not fit the other classifications—HIV-negative patients without detectable cellular or humoral immune deficiency. This subset has been described as clinically similar to classic KS with limited disease but occurring in younger men.^2,3 We describe a case of nonepidemic KS in a Middle Eastern heterosexual immunocompetent man.

A 30-year-old man presented for evaluation of a growth on the nose of 3 months’ duration. The patient reported being otherwise healthy and was not taking long-term medications. He denied a history of malignancy, organ transplant, or immunosuppressive therapy. He was born in Syria and lived in Thailand for several years prior to moving to the United States. HIV testing 6 months prior to presentation was negative. He denied fever, chills, lymphadenopathy, shortness of breath, hemoptysis, melena, hematochezia, and intravenous drug use.

Physical examination revealed a solitary shiny, 7-mm, pink-red papule on the nasal dorsum (Figure 1). No other skin or mucosal lesions were identified. There was no cervical, axillary, or inguinal lymphadenopathy. A laboratory workup consisting of serum immunoglobulins and serum protein electrophoresis was unremarkable. Tests for HIV-1 and HIV-2 as well as human T-lymphotropic virus 1 and 2 were negative. The CD4 and CD8 counts were within reference range. Histopathology of a shave biopsy revealed a dermal spindle cell proliferation arranged in short intersecting fascicles and admixed with plasma cells and occasional mitotic figures. Immunohistochemistry showed that the spindle cells stained positive for CD34, CD31, and HHV-8 (Figure 2). The lesion resolved after treatment with cryotherapy. Repeat HIV testing 3 months later was negative. No recurrence or new lesions were identified at 3-month follow-up.

Similar to the other subtypes of KS, the nonepidemic form is dependent on HHV-8 infection, which is more commonly transmitted via saliva and sexual contact.^3,4 After infecting endothelial cells, HHV-8 is believed to activate the mammalian target of rapamycin and nuclear factor κB pathways, resulting in aberrant cellular differentiation and neoangiogenesis through upregulation of vascular endothelial growth factor and basic fibroblast growth factor.^2,4 Similar to what is seen with other herpesviruses, HHV-8 infection typically is lifelong due to the virus’s ability to establish latency within human B cells and endothelial cells as well as undergo sporadic bouts of lytic reactivation during its life cycle.⁴

Nonepidemic KS resembles other variants clinically, manifesting as erythematous or violaceous, painless, nonblanchable macules, papules, and nodules.¹ Early lesions often are asymptomatic and can manifest as pigmented macules or small papules that vary from pale pink to vivid purple. Nodules also can occur and be exophytic and ulcerated with bleeding.¹ Secondary lymphoproliferative disorders including Castleman disease and lymphoma have been reported.^2,5

In contrast to other types of KS in which pulmonary or gastrointestinal tract lesions can develop with hemoptysis or hematochezia, mucocutaneous and visceral lesions rarely are reported in nonepidemic KS.³ Lymphedema, a feature associated with endemic KS, is notably absent in nonepidemic KS.^1,3

The differential diagnosis applicable to all KS subtypes includes other vascular lesions such as angiomatosis and angiosarcoma. Histopathologic analysis is critical to differentiate KS from these conditions; visual diagnosis alone has only an 80% positive predictive value for KS.⁴ The histopathologic presentation of KS is a vascular proliferation in the dermis accompanied by an increased number of vessels without an endothelial cell lining.⁴ Spindle cell proliferation also is a common feature and is considered to be the KS tumor cell. Immunostaining for HHV-8 antigen as well as for CD31 and CD34 can be used to confirm the diagnosis.⁴

The management and prognosis of KS depends on the epidemiologic subtype. Classic and nonepidemic KS generally are indolent with a good prognosis. Periodic follow-up is recommended because of an increased risk for secondary malignancy such as lymphoma. The treatment of epidemic KS is highly active antiretroviral therapy. Similarly, reduction of immunosuppression is warranted for iatrogenic KS. For all types, cutaneous lesions can be treated with local excision, cryosurgery, radiation, chemotherapy, intralesional vincristine, or a topical agent such as imiquimod or alitretinoin.⁶

To the Editor:

Kaposi sarcoma (KS) is a rare angioproliferative disorder associated with human herpesvirus 8 (HHV-8) infection.¹ There are 4 main recognized epidemiologic forms of KS: classic, endemic, epidemic, and iatrogenic (Table). Nonepidemic KS is a recently described rare fifth type of KS that occurs in a subset of patients who do not fit the other classifications—HIV-negative patients without detectable cellular or humoral immune deficiency. This subset has been described as clinically similar to classic KS with limited disease but occurring in younger men.^2,3 We describe a case of nonepidemic KS in a Middle Eastern heterosexual immunocompetent man.

A 30-year-old man presented for evaluation of a growth on the nose of 3 months’ duration. The patient reported being otherwise healthy and was not taking long-term medications. He denied a history of malignancy, organ transplant, or immunosuppressive therapy. He was born in Syria and lived in Thailand for several years prior to moving to the United States. HIV testing 6 months prior to presentation was negative. He denied fever, chills, lymphadenopathy, shortness of breath, hemoptysis, melena, hematochezia, and intravenous drug use.

Physical examination revealed a solitary shiny, 7-mm, pink-red papule on the nasal dorsum (Figure 1). No other skin or mucosal lesions were identified. There was no cervical, axillary, or inguinal lymphadenopathy. A laboratory workup consisting of serum immunoglobulins and serum protein electrophoresis was unremarkable. Tests for HIV-1 and HIV-2 as well as human T-lymphotropic virus 1 and 2 were negative. The CD4 and CD8 counts were within reference range. Histopathology of a shave biopsy revealed a dermal spindle cell proliferation arranged in short intersecting fascicles and admixed with plasma cells and occasional mitotic figures. Immunohistochemistry showed that the spindle cells stained positive for CD34, CD31, and HHV-8 (Figure 2). The lesion resolved after treatment with cryotherapy. Repeat HIV testing 3 months later was negative. No recurrence or new lesions were identified at 3-month follow-up.

Similar to the other subtypes of KS, the nonepidemic form is dependent on HHV-8 infection, which is more commonly transmitted via saliva and sexual contact.^3,4 After infecting endothelial cells, HHV-8 is believed to activate the mammalian target of rapamycin and nuclear factor κB pathways, resulting in aberrant cellular differentiation and neoangiogenesis through upregulation of vascular endothelial growth factor and basic fibroblast growth factor.^2,4 Similar to what is seen with other herpesviruses, HHV-8 infection typically is lifelong due to the virus’s ability to establish latency within human B cells and endothelial cells as well as undergo sporadic bouts of lytic reactivation during its life cycle.⁴

Nonepidemic KS resembles other variants clinically, manifesting as erythematous or violaceous, painless, nonblanchable macules, papules, and nodules.¹ Early lesions often are asymptomatic and can manifest as pigmented macules or small papules that vary from pale pink to vivid purple. Nodules also can occur and be exophytic and ulcerated with bleeding.¹ Secondary lymphoproliferative disorders including Castleman disease and lymphoma have been reported.^2,5

In contrast to other types of KS in which pulmonary or gastrointestinal tract lesions can develop with hemoptysis or hematochezia, mucocutaneous and visceral lesions rarely are reported in nonepidemic KS.³ Lymphedema, a feature associated with endemic KS, is notably absent in nonepidemic KS.^1,3

The differential diagnosis applicable to all KS subtypes includes other vascular lesions such as angiomatosis and angiosarcoma. Histopathologic analysis is critical to differentiate KS from these conditions; visual diagnosis alone has only an 80% positive predictive value for KS.⁴ The histopathologic presentation of KS is a vascular proliferation in the dermis accompanied by an increased number of vessels without an endothelial cell lining.⁴ Spindle cell proliferation also is a common feature and is considered to be the KS tumor cell. Immunostaining for HHV-8 antigen as well as for CD31 and CD34 can be used to confirm the diagnosis.⁴

The management and prognosis of KS depends on the epidemiologic subtype. Classic and nonepidemic KS generally are indolent with a good prognosis. Periodic follow-up is recommended because of an increased risk for secondary malignancy such as lymphoma. The treatment of epidemic KS is highly active antiretroviral therapy. Similarly, reduction of immunosuppression is warranted for iatrogenic KS. For all types, cutaneous lesions can be treated with local excision, cryosurgery, radiation, chemotherapy, intralesional vincristine, or a topical agent such as imiquimod or alitretinoin.⁶

To the Editor:

Kaposi sarcoma (KS) is a rare angioproliferative disorder associated with human herpesvirus 8 (HHV-8) infection.¹ There are 4 main recognized epidemiologic forms of KS: classic, endemic, epidemic, and iatrogenic (Table). Nonepidemic KS is a recently described rare fifth type of KS that occurs in a subset of patients who do not fit the other classifications—HIV-negative patients without detectable cellular or humoral immune deficiency. This subset has been described as clinically similar to classic KS with limited disease but occurring in younger men.^2,3 We describe a case of nonepidemic KS in a Middle Eastern heterosexual immunocompetent man.

A 30-year-old man presented for evaluation of a growth on the nose of 3 months’ duration. The patient reported being otherwise healthy and was not taking long-term medications. He denied a history of malignancy, organ transplant, or immunosuppressive therapy. He was born in Syria and lived in Thailand for several years prior to moving to the United States. HIV testing 6 months prior to presentation was negative. He denied fever, chills, lymphadenopathy, shortness of breath, hemoptysis, melena, hematochezia, and intravenous drug use.

Physical examination revealed a solitary shiny, 7-mm, pink-red papule on the nasal dorsum (Figure 1). No other skin or mucosal lesions were identified. There was no cervical, axillary, or inguinal lymphadenopathy. A laboratory workup consisting of serum immunoglobulins and serum protein electrophoresis was unremarkable. Tests for HIV-1 and HIV-2 as well as human T-lymphotropic virus 1 and 2 were negative. The CD4 and CD8 counts were within reference range. Histopathology of a shave biopsy revealed a dermal spindle cell proliferation arranged in short intersecting fascicles and admixed with plasma cells and occasional mitotic figures. Immunohistochemistry showed that the spindle cells stained positive for CD34, CD31, and HHV-8 (Figure 2). The lesion resolved after treatment with cryotherapy. Repeat HIV testing 3 months later was negative. No recurrence or new lesions were identified at 3-month follow-up.

Similar to the other subtypes of KS, the nonepidemic form is dependent on HHV-8 infection, which is more commonly transmitted via saliva and sexual contact.^3,4 After infecting endothelial cells, HHV-8 is believed to activate the mammalian target of rapamycin and nuclear factor κB pathways, resulting in aberrant cellular differentiation and neoangiogenesis through upregulation of vascular endothelial growth factor and basic fibroblast growth factor.^2,4 Similar to what is seen with other herpesviruses, HHV-8 infection typically is lifelong due to the virus’s ability to establish latency within human B cells and endothelial cells as well as undergo sporadic bouts of lytic reactivation during its life cycle.⁴

Nonepidemic KS resembles other variants clinically, manifesting as erythematous or violaceous, painless, nonblanchable macules, papules, and nodules.¹ Early lesions often are asymptomatic and can manifest as pigmented macules or small papules that vary from pale pink to vivid purple. Nodules also can occur and be exophytic and ulcerated with bleeding.¹ Secondary lymphoproliferative disorders including Castleman disease and lymphoma have been reported.^2,5

In contrast to other types of KS in which pulmonary or gastrointestinal tract lesions can develop with hemoptysis or hematochezia, mucocutaneous and visceral lesions rarely are reported in nonepidemic KS.³ Lymphedema, a feature associated with endemic KS, is notably absent in nonepidemic KS.^1,3

The differential diagnosis applicable to all KS subtypes includes other vascular lesions such as angiomatosis and angiosarcoma. Histopathologic analysis is critical to differentiate KS from these conditions; visual diagnosis alone has only an 80% positive predictive value for KS.⁴ The histopathologic presentation of KS is a vascular proliferation in the dermis accompanied by an increased number of vessels without an endothelial cell lining.⁴ Spindle cell proliferation also is a common feature and is considered to be the KS tumor cell. Immunostaining for HHV-8 antigen as well as for CD31 and CD34 can be used to confirm the diagnosis.⁴

The management and prognosis of KS depends on the epidemiologic subtype. Classic and nonepidemic KS generally are indolent with a good prognosis. Periodic follow-up is recommended because of an increased risk for secondary malignancy such as lymphoma. The treatment of epidemic KS is highly active antiretroviral therapy. Similarly, reduction of immunosuppression is warranted for iatrogenic KS. For all types, cutaneous lesions can be treated with local excision, cryosurgery, radiation, chemotherapy, intralesional vincristine, or a topical agent such as imiquimod or alitretinoin.⁶

“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.

That is certainly not the case right now in some parts of Europe. The World Health Organization (WHO) says the European Region is experiencing an alarming rise in cases, and urgent action is needed. Healthcare professionals are trying to gain control over measles outbreaks and roll out vaccination catch-up campaigns.

“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
 

Lapses in Vaccinations

The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.

“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”

Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.

“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
 

Variation Across Europe

The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.

Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.

The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.

“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”

Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.

She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”

Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
 

Vaccine Hesitance

Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.

“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”

The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).

But the MMR vaccine backslide does not only originate in the pandemic.

Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”

It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.

Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
 

Clinics and Catch-Up Campaigns

Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.

Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.

“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.

“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”

All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
 

When Will It Get Back to Normal?

“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.

Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”

Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
 

A version of this article appeared on Medscape.com.

“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.

That is certainly not the case right now in some parts of Europe. The World Health Organization (WHO) says the European Region is experiencing an alarming rise in cases, and urgent action is needed. Healthcare professionals are trying to gain control over measles outbreaks and roll out vaccination catch-up campaigns.

“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
 

Lapses in Vaccinations

The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.

“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”

Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.

“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
 

Variation Across Europe

The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.

Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.

The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.

“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”

Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.

She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”

Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
 

Vaccine Hesitance

Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.

“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”

The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).

But the MMR vaccine backslide does not only originate in the pandemic.

Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”

It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.

Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
 

Clinics and Catch-Up Campaigns

Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.

Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.

“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.

“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”

All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
 

When Will It Get Back to Normal?

“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.

Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”

Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
 

A version of this article appeared on Medscape.com.

“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.

That is certainly not the case right now in some parts of Europe. The World Health Organization (WHO) says the European Region is experiencing an alarming rise in cases, and urgent action is needed. Healthcare professionals are trying to gain control over measles outbreaks and roll out vaccination catch-up campaigns.

“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
 

Lapses in Vaccinations

The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.

“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”

Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.

“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
 

Variation Across Europe

The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.

Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.

The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.

“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”

Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.

She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”

Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
 

Vaccine Hesitance

Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.

“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”

The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).

But the MMR vaccine backslide does not only originate in the pandemic.

Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”

It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.

Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
 

Clinics and Catch-Up Campaigns

Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.

Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.

“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.

“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”

All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
 

When Will It Get Back to Normal?

“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.

Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”

Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
 

A version of this article appeared on Medscape.com.

Children and adolescents ages 5-17 who received a bivalent COVID-19 mRNA vaccine were less likely to become infected with SARS-CoV-2 compared with those who were unvaccinated or received only the monovalent COVID-19 vaccine, according to new data published February 6 in JAMA.

“All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations,” wrote the authors, led by Leora R. Feldstein, PhD, with the US Centers for Disease Control and Prevention (CDC) in Atlanta.

By the end of 2023, at least 911 youths ages 5-17 had died from COVID-related causes.

Researchers found that compared with participants who did not receive the COVID-19 vaccine or got monovalent-only doses 180 days or more before, the adjusted vaccine effectiveness of a bivalent COVID-19 vaccine dose against SARS-CoV-2 infection was 51.3% (95% confidence interval [CI], 23.6%-71.9%) 7-60 days after vaccination. Relative effectiveness was 62.4% (95% CI, 38.5%-81.1%) 61-150 days after vaccination. The researchers said the confidence intervals were wide because of the small sample size.

The information can help inform public health strategies, the authors noted, especially as new variants emerge.
 

Bivalent Dose Recommended in Fall of 2022

Bivalent mRNA COVID vaccines were recommended in the United States for children and adolescents ages 12 years or older on Sept. 1, 2022, and for children ages 5-11 on Oct. 12, 2022, when Omicron BA.4/5 types were the predominant circulating variant.

The study included 2,959 participants who completed periodic surveys (answering questions on demographics, household details, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (whether or not they had symptoms). Those in the study submitted additional nasal swabs if they developed any symptoms.

Median adherence to weekly upper respiratory specimen swabbing was high throughout the study period at 93.8%.

Data from Sept. 4, 2022, to Jan. 31, 2023, were combined from three prospective US cohort studies at six sites. In addition to the surveys, researchers used information from state immunization information systems and electronic medical records.
 

Most of the Infected Were Unvaccinated or Had Monovalent Vax

Of the 426 participants (14.4% of the combined cohorts) infected with SARS-CoV-2, 383 (89.9%) were either unvaccinated or received monovalent vaccine doses only.

Calculations were adjusted for age, sex, race, ethnicity, health conditions, prior SARS-CoV-2 infections, geographic location, proportion of circulating variants by site, and local virus prevalence.

Participants living in Oregon, for example, had the highest uptake of bivalent COVID-19 vaccine (56.2%), whereas those in Texas had the lowest (2.4%). Participants reporting Hispanic ethnicity had lower bivalent uptake (17.1%) compared with non-Hispanic participants of all races (27.1%).

Of the 2,207 participants who did not receive a bivalent dose, 24.2% were unvaccinated and 1,672 (75.8%) received at least 1 monovalent dose.

The researchers said they saw no sign of waning effectiveness 61-150 days (the limit for this analysis) after receipt of the bivalent COVID-19 vaccine.

They wrote that continuation of the cohorts will allow study of waning patterns, which could help inform vaccine recommendations.

Among the limitations of the study are that testing methods and the COVID-19 symptoms surveyed varied among the three cohorts, so there may be some differences in defining infection or symptomatic COVID. In addition, the researchers were not able to account for the social vulnerability index and immunocompromised status, which could have affected vaccine uptake and risk of SARS-CoV-2 infection.

This study was supported by the National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, and by the National Institute of Allergy and Infectious Diseases. Coauthor Dr. Caban-Martinez reported grants from the Florida Firefighter Cancer Initiative and the Florida Department of Health. Coauthors Dr. Chu, Dr. Englund, Dr. Martin, and Dr. Monto reported receiving personal fees or grants from multiple pharmaceutical companies. Dr. Hegmann reported being the editor of the American College of Occupational and Environmental Medicine practice guidelines. Coauthor Dr. Gaglani reported serving as cochair of the infectious diseases and immunization committee and the respiratory syncytial virus task force lead for the Texas Pediatric Society and the Texas Chapter of the American Academy of Pediatrics. No other disclosures were reported.

Children and adolescents ages 5-17 who received a bivalent COVID-19 mRNA vaccine were less likely to become infected with SARS-CoV-2 compared with those who were unvaccinated or received only the monovalent COVID-19 vaccine, according to new data published February 6 in JAMA.

“All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations,” wrote the authors, led by Leora R. Feldstein, PhD, with the US Centers for Disease Control and Prevention (CDC) in Atlanta.

By the end of 2023, at least 911 youths ages 5-17 had died from COVID-related causes.

Researchers found that compared with participants who did not receive the COVID-19 vaccine or got monovalent-only doses 180 days or more before, the adjusted vaccine effectiveness of a bivalent COVID-19 vaccine dose against SARS-CoV-2 infection was 51.3% (95% confidence interval [CI], 23.6%-71.9%) 7-60 days after vaccination. Relative effectiveness was 62.4% (95% CI, 38.5%-81.1%) 61-150 days after vaccination. The researchers said the confidence intervals were wide because of the small sample size.

The information can help inform public health strategies, the authors noted, especially as new variants emerge.
 

Bivalent Dose Recommended in Fall of 2022

Bivalent mRNA COVID vaccines were recommended in the United States for children and adolescents ages 12 years or older on Sept. 1, 2022, and for children ages 5-11 on Oct. 12, 2022, when Omicron BA.4/5 types were the predominant circulating variant.

The study included 2,959 participants who completed periodic surveys (answering questions on demographics, household details, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (whether or not they had symptoms). Those in the study submitted additional nasal swabs if they developed any symptoms.

Median adherence to weekly upper respiratory specimen swabbing was high throughout the study period at 93.8%.

Data from Sept. 4, 2022, to Jan. 31, 2023, were combined from three prospective US cohort studies at six sites. In addition to the surveys, researchers used information from state immunization information systems and electronic medical records.
 

Most of the Infected Were Unvaccinated or Had Monovalent Vax

Of the 426 participants (14.4% of the combined cohorts) infected with SARS-CoV-2, 383 (89.9%) were either unvaccinated or received monovalent vaccine doses only.

Calculations were adjusted for age, sex, race, ethnicity, health conditions, prior SARS-CoV-2 infections, geographic location, proportion of circulating variants by site, and local virus prevalence.

Participants living in Oregon, for example, had the highest uptake of bivalent COVID-19 vaccine (56.2%), whereas those in Texas had the lowest (2.4%). Participants reporting Hispanic ethnicity had lower bivalent uptake (17.1%) compared with non-Hispanic participants of all races (27.1%).

Of the 2,207 participants who did not receive a bivalent dose, 24.2% were unvaccinated and 1,672 (75.8%) received at least 1 monovalent dose.

The researchers said they saw no sign of waning effectiveness 61-150 days (the limit for this analysis) after receipt of the bivalent COVID-19 vaccine.

They wrote that continuation of the cohorts will allow study of waning patterns, which could help inform vaccine recommendations.

Among the limitations of the study are that testing methods and the COVID-19 symptoms surveyed varied among the three cohorts, so there may be some differences in defining infection or symptomatic COVID. In addition, the researchers were not able to account for the social vulnerability index and immunocompromised status, which could have affected vaccine uptake and risk of SARS-CoV-2 infection.

This study was supported by the National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, and by the National Institute of Allergy and Infectious Diseases. Coauthor Dr. Caban-Martinez reported grants from the Florida Firefighter Cancer Initiative and the Florida Department of Health. Coauthors Dr. Chu, Dr. Englund, Dr. Martin, and Dr. Monto reported receiving personal fees or grants from multiple pharmaceutical companies. Dr. Hegmann reported being the editor of the American College of Occupational and Environmental Medicine practice guidelines. Coauthor Dr. Gaglani reported serving as cochair of the infectious diseases and immunization committee and the respiratory syncytial virus task force lead for the Texas Pediatric Society and the Texas Chapter of the American Academy of Pediatrics. No other disclosures were reported.

Children and adolescents ages 5-17 who received a bivalent COVID-19 mRNA vaccine were less likely to become infected with SARS-CoV-2 compared with those who were unvaccinated or received only the monovalent COVID-19 vaccine, according to new data published February 6 in JAMA.

“All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations,” wrote the authors, led by Leora R. Feldstein, PhD, with the US Centers for Disease Control and Prevention (CDC) in Atlanta.

By the end of 2023, at least 911 youths ages 5-17 had died from COVID-related causes.

Researchers found that compared with participants who did not receive the COVID-19 vaccine or got monovalent-only doses 180 days or more before, the adjusted vaccine effectiveness of a bivalent COVID-19 vaccine dose against SARS-CoV-2 infection was 51.3% (95% confidence interval [CI], 23.6%-71.9%) 7-60 days after vaccination. Relative effectiveness was 62.4% (95% CI, 38.5%-81.1%) 61-150 days after vaccination. The researchers said the confidence intervals were wide because of the small sample size.

The information can help inform public health strategies, the authors noted, especially as new variants emerge.
 

Bivalent Dose Recommended in Fall of 2022

Bivalent mRNA COVID vaccines were recommended in the United States for children and adolescents ages 12 years or older on Sept. 1, 2022, and for children ages 5-11 on Oct. 12, 2022, when Omicron BA.4/5 types were the predominant circulating variant.

The study included 2,959 participants who completed periodic surveys (answering questions on demographics, household details, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (whether or not they had symptoms). Those in the study submitted additional nasal swabs if they developed any symptoms.

Median adherence to weekly upper respiratory specimen swabbing was high throughout the study period at 93.8%.

Data from Sept. 4, 2022, to Jan. 31, 2023, were combined from three prospective US cohort studies at six sites. In addition to the surveys, researchers used information from state immunization information systems and electronic medical records.
 

Most of the Infected Were Unvaccinated or Had Monovalent Vax

Of the 426 participants (14.4% of the combined cohorts) infected with SARS-CoV-2, 383 (89.9%) were either unvaccinated or received monovalent vaccine doses only.

Calculations were adjusted for age, sex, race, ethnicity, health conditions, prior SARS-CoV-2 infections, geographic location, proportion of circulating variants by site, and local virus prevalence.

Participants living in Oregon, for example, had the highest uptake of bivalent COVID-19 vaccine (56.2%), whereas those in Texas had the lowest (2.4%). Participants reporting Hispanic ethnicity had lower bivalent uptake (17.1%) compared with non-Hispanic participants of all races (27.1%).

Of the 2,207 participants who did not receive a bivalent dose, 24.2% were unvaccinated and 1,672 (75.8%) received at least 1 monovalent dose.

The researchers said they saw no sign of waning effectiveness 61-150 days (the limit for this analysis) after receipt of the bivalent COVID-19 vaccine.

They wrote that continuation of the cohorts will allow study of waning patterns, which could help inform vaccine recommendations.

Among the limitations of the study are that testing methods and the COVID-19 symptoms surveyed varied among the three cohorts, so there may be some differences in defining infection or symptomatic COVID. In addition, the researchers were not able to account for the social vulnerability index and immunocompromised status, which could have affected vaccine uptake and risk of SARS-CoV-2 infection.

This study was supported by the National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention, and by the National Institute of Allergy and Infectious Diseases. Coauthor Dr. Caban-Martinez reported grants from the Florida Firefighter Cancer Initiative and the Florida Department of Health. Coauthors Dr. Chu, Dr. Englund, Dr. Martin, and Dr. Monto reported receiving personal fees or grants from multiple pharmaceutical companies. Dr. Hegmann reported being the editor of the American College of Occupational and Environmental Medicine practice guidelines. Coauthor Dr. Gaglani reported serving as cochair of the infectious diseases and immunization committee and the respiratory syncytial virus task force lead for the Texas Pediatric Society and the Texas Chapter of the American Academy of Pediatrics. No other disclosures were reported.

Characteristics

Rhipicephalus ticks belong to the Ixodidae family of hard-bodied ticks. They are large and teardrop shaped with an inornate scutum (hard dorsal plate) and relatively short mouthparts attached at a hexagonal basis capitulum (base of the head to which mouthparts are attached)(Figure).¹ Widely spaced eyes and festoons also are present. The first pair of coxae—attachment base for the first pair of legs—are characteristically bifid; males have a pair of sclerotized adanal plates on the ventral surface adjacent to the anus as well as accessory adanal shields.²Rhipicephalus (formerly Boophilus) microplus (the so-called cattle tick) is a newly added species; it lacks posterior festoons, and the anal groove is absent.³

Almost all Rhipicephalus ticks, except for R microplus, are 3-host ticks in which a single blood meal is consumed from a vertebrate host at each active life stage—larva, nymph, and adult—to complete development.^4,5 In contrast to most ixodid ticks, which are exophilic (living outside of human habitation), the Rhipicephalus sanguineus sensu lato species (the brown dog tick) is highly endophilic (adapted to indoor living) and often can be found hidden in cracks and crevices of walls in homes and peridomestic structures.⁶ It is predominately monotropic (all developmental stages feed on the same host species) and has a strong host preference for dogs, though it occasionally feeds on other hosts (eg, humans).⁷ Although most common in tropical and subtropical climates, they can be found anywhere there are dogs due to their ability to colonize indoor dwellings.⁸ In contrast, R microplus ticks have a predilection for cattle and livestock rather than humans, posing a notable concern to livestock worldwide. Infestation results in transmission of disease-causing pathogens, such as Babesia and Anaplasma species, which costs the cattle industry billions of dollars annually.⁹

Clinical Manifestations and Treatment

Tick bites usually manifest as intensely pruritic, erythematous papules at the site of tick attachment due to a local type IV hypersensitivity reaction to antigens in the tick’s saliva. This reaction can be long-lasting. In addition to pruritic papules following a bite, an attached tick can be mistaken for a skin neoplasm or nevus. Given that ticks are small, especially during the larval stage, dermoscopy may be helpful in making a diagnosis.¹⁰ Symptomatic relief usually can be achieved with topical antipruritics or oral antihistamines.

Of public health concern, brown dog ticks are important vectors of Rickettsia rickettsii (the causative organism of Rocky Mountain spotted fever [RMSF]) in the Western hemisphere, and Rickettsia conorii (the causative organism of Mediterranean spotted fever [MSF][also known as Boutonneuse fever]) in the Eastern hemisphere.¹¹ Bites by ticks carrying rickettsial disease classically manifest with early symptoms of fever, headache, and myalgia, followed by a rash or by a localized eschar or tache noire (a black, necrotic, scabbed lesion) that represents direct endothelial invasion and vascular damage by Rickettsia.¹² Rocky Mountain spotted fever and MSF are more prevalent during summer, likely due, in part, to the combination of increased outdoor activity and a higher rate of tick-questing (host-seeking) behavior in warmer climates.^4,7

Rocky Mountain Spotted Fever—Dermacentor variabilis is the primary vector of RMSF in the southeastern United States; Dermacentor andersoni is the major vector of RMSF in Rocky Mountain states. Rhipicephalus sanguineus sensu lato is an important vector of RMSF in the southwestern United States, Mexico, and Central America.^11,13

Early symptoms of RMSF are nonspecific and can include fever, headache, arthralgia, myalgia, and malaise. Gastrointestinal tract symptoms (eg, nausea, vomiting, anorexia) may occur; notable abdominal pain occurs in some patients, particularly children. A characteristic petechial rash occurs in as many as 90% of patients, typically at the third to fifth day of illness, and classically begins on the wrists and ankles, with progression to the palms and soles before spreading centripetally to the arms, legs, and trunk.¹⁴ An eschar at the inoculation site is uncommon in RMSF; when present, it is more suggestive of MSF.¹⁵

The classic triad of fever, headache, and rash is present in 3% of patients during the first 3 days after a tick bite and in 60% to 70% within 2 weeks.¹⁶ A rash often is absent when patients first seek medical attention and may not develop (absent in 9% to 12% of cases; so-called spotless RMSF). Therefore, absence of rash should not be a reason to withhold treatment.¹⁶ Empiric treatment with doxycycline should be started promptly for all suspected cases of RMSF because of the rapid progression of disease and an increased risk for morbidity and mortality with delayed diagnosis.

Patients do not become antibody positive until 7 to 10 days after symptoms begin; therefore, treatment should not be delayed while awaiting serologic test results. The case fatality rate in the United States is estimated to be 5% to 10% overall and as high as 40% to 50% among patients who are not treated until day 8 or 9 of illness.¹⁷

Cutaneous complications include skin necrosis and gangrene due to continuous tissue damage in severe cases.¹⁶ Severe infection also may manifest with signs of multiorgan system damage, including altered mental status, cerebral edema, meningismus, transient deafness, myocarditis, pulmonary hemorrhage and edema, conjunctivitis, retinal abnormalities, and acute renal failure.^14,16 Risk factors for more severe illness include delayed treatment, age 40 years or older or younger than 10 years, and underlying medical conditions such as alcoholic liver disease and glucose-6-phosphate dehydrogenase deficiency. However, even some healthy young patients die of this disease.¹⁷

Mediterranean Spotted Fever—Rhipicephalus sanguineus sensu lato is the primary vector of MSF, which is prevalent in areas adjacent to the Mediterranean Sea, including southern Europe, Africa, and Central Asia; Sicily is the most highly affected region.¹⁸ Findings with MSF are nearly identical to those of RMSF, except that tache noire is more common, present in as many as 70% of cases at the site of the inoculating tick bite, and MSF typically follows a less severe clinical course.¹² Similar to other rickettsial diseases, the pathogenesis of MSF involves direct injury to vascular endothelial cells, causing a vasculitis that is responsible for the clinical abnormalities observed.

Patients with severe MSF experience complications similar to severe RMSF, including neurologic manifestations and multiorgan damage.¹⁸ Risk factors include advanced age, immunocompromised state, cardiac disease, chronic alcoholism, diabetes mellitus, glucose-6-phosphate dehydrogenase deficiency, respiratory insufficiency, and delayed treatment.¹⁸

Treatment—For all spotted fever group rickettsial infections, doxycycline is the treatment of choice for all patients, including children and pregnant women. Treatment should be started without delay; recommended dosages are 100 mg twice daily for children weighing more than 45 kg and adults, and 2.2 mg/kg twice daily for children weighing 45 kg or less.¹²

Rhipicephalus tick bites rarely can result in paralysis; however, Dermacentor ticks are responsible for most cases of tick-related paralysis in North America. Other pathogens proven or reputed to be transmitted by Rhipicephalus sanguineus sensu lato with zoonotic potential include but are not limited to Rickettsia massiliae, Coxiella burnetti, Anaplasma platys, Leishmania infantum, and Crimean-Congo hemorrhagic fever virus (Nairovirus).¹⁹

Environmental Treatment and Prevention

The most effective way to prevent tick-borne illness is avoidance of tick bites. Primary prevention methods include vector control, use of repellents (eg, N,N-diethyl-meta-toluamide [DEET]), picaridin, permethrin), avoidance of areas with a high tick burden, use of protective clothing, and detection and removal of ticks as soon as possible.

Environmental and veterinary controls also are important methods of tick-bite prevention. A veterinarian can recommend a variety of agents for dogs and cats that prevent attachment of ticks. Environmental controls include synthetic or natural product-based chemical acaricides and nonchemical methods, such as landscape management (eg, sealing cracks and crevices in homes and controlling tall grasses, weeds, and leaf debris) to minimize potential tick habitat.²⁰ Secondary prevention includes antibiotics for prophylaxis or for treatment of tick-borne disease, when indicated.

Numerous tick repellents are available commercially; others are being studied. DEET, the most widely used topical repellent, has a broad spectrum of activity against many tick species.²¹ In addition, DEET has a well-known safety and toxicity profile, with rare adverse effects, and is safe for use in pregnant women and children older than 2 years. Alternative repellents, such as those containing picaridin, ethyl butylacetylaminopropionate (IR3535 [Merck]), oil of lemon eucalyptus, and 2-undecanone can be effective; some show efficacy comparable to that of DEET.²² Permethrin, a synthetic pyrethroid, is a highly efficacious tick repellent and insecticide, especially when used in conjunction with a topical repellent such as DEET. Unlike topically applied repellents, permethrin spray is applied to fabric (eg, clothing, shoes, bed nets, camping gear), not to skin.

Indiscriminate use of acaricides worldwide has led to increasing selection of acaricide resistance in Rhipicephalus tick species, which is especially true with the use of acaricides in controlling R microplus livestock infestations; several tick populations now show resistance to all major classes of these compounds.^23-25 For that reason, there has been an increasing effort to develop new chemical and nonchemical approaches to tick control that are more environmentally sustainable and strategies to minimize development and progression of resistance such as rotation of acaricides; reducing the frequency of their application; use of pesticide mixtures, synergists, or both; and increasing use of nonacaricidal methods of control.²⁶

Prompt removal of ticks is important for preventing the transmission of tick-borne disease. Proper removal involves rubbing the tick in a circular motion with a moist gauze pad or using fine-tipped tweezers to grasp the tick as close to the skin surface as possible and pulling upward with a steady pressure.^17,27 It is important not to jerk, twist, squeeze, smash, or burn the tick, as this can result in insufficient removal of mouthparts or spread contaminated tick fluids to mucous membranes, increasing the risk for infection. Application of petroleum jelly or nail polish to aid in tick removal have not been shown to be effective and are not recommended.^16,28

Characteristics

Rhipicephalus ticks belong to the Ixodidae family of hard-bodied ticks. They are large and teardrop shaped with an inornate scutum (hard dorsal plate) and relatively short mouthparts attached at a hexagonal basis capitulum (base of the head to which mouthparts are attached)(Figure).¹ Widely spaced eyes and festoons also are present. The first pair of coxae—attachment base for the first pair of legs—are characteristically bifid; males have a pair of sclerotized adanal plates on the ventral surface adjacent to the anus as well as accessory adanal shields.²Rhipicephalus (formerly Boophilus) microplus (the so-called cattle tick) is a newly added species; it lacks posterior festoons, and the anal groove is absent.³

Almost all Rhipicephalus ticks, except for R microplus, are 3-host ticks in which a single blood meal is consumed from a vertebrate host at each active life stage—larva, nymph, and adult—to complete development.^4,5 In contrast to most ixodid ticks, which are exophilic (living outside of human habitation), the Rhipicephalus sanguineus sensu lato species (the brown dog tick) is highly endophilic (adapted to indoor living) and often can be found hidden in cracks and crevices of walls in homes and peridomestic structures.⁶ It is predominately monotropic (all developmental stages feed on the same host species) and has a strong host preference for dogs, though it occasionally feeds on other hosts (eg, humans).⁷ Although most common in tropical and subtropical climates, they can be found anywhere there are dogs due to their ability to colonize indoor dwellings.⁸ In contrast, R microplus ticks have a predilection for cattle and livestock rather than humans, posing a notable concern to livestock worldwide. Infestation results in transmission of disease-causing pathogens, such as Babesia and Anaplasma species, which costs the cattle industry billions of dollars annually.⁹

Clinical Manifestations and Treatment

Tick bites usually manifest as intensely pruritic, erythematous papules at the site of tick attachment due to a local type IV hypersensitivity reaction to antigens in the tick’s saliva. This reaction can be long-lasting. In addition to pruritic papules following a bite, an attached tick can be mistaken for a skin neoplasm or nevus. Given that ticks are small, especially during the larval stage, dermoscopy may be helpful in making a diagnosis.¹⁰ Symptomatic relief usually can be achieved with topical antipruritics or oral antihistamines.

Of public health concern, brown dog ticks are important vectors of Rickettsia rickettsii (the causative organism of Rocky Mountain spotted fever [RMSF]) in the Western hemisphere, and Rickettsia conorii (the causative organism of Mediterranean spotted fever [MSF][also known as Boutonneuse fever]) in the Eastern hemisphere.¹¹ Bites by ticks carrying rickettsial disease classically manifest with early symptoms of fever, headache, and myalgia, followed by a rash or by a localized eschar or tache noire (a black, necrotic, scabbed lesion) that represents direct endothelial invasion and vascular damage by Rickettsia.¹² Rocky Mountain spotted fever and MSF are more prevalent during summer, likely due, in part, to the combination of increased outdoor activity and a higher rate of tick-questing (host-seeking) behavior in warmer climates.^4,7

Rocky Mountain Spotted Fever—Dermacentor variabilis is the primary vector of RMSF in the southeastern United States; Dermacentor andersoni is the major vector of RMSF in Rocky Mountain states. Rhipicephalus sanguineus sensu lato is an important vector of RMSF in the southwestern United States, Mexico, and Central America.^11,13

Early symptoms of RMSF are nonspecific and can include fever, headache, arthralgia, myalgia, and malaise. Gastrointestinal tract symptoms (eg, nausea, vomiting, anorexia) may occur; notable abdominal pain occurs in some patients, particularly children. A characteristic petechial rash occurs in as many as 90% of patients, typically at the third to fifth day of illness, and classically begins on the wrists and ankles, with progression to the palms and soles before spreading centripetally to the arms, legs, and trunk.¹⁴ An eschar at the inoculation site is uncommon in RMSF; when present, it is more suggestive of MSF.¹⁵

The classic triad of fever, headache, and rash is present in 3% of patients during the first 3 days after a tick bite and in 60% to 70% within 2 weeks.¹⁶ A rash often is absent when patients first seek medical attention and may not develop (absent in 9% to 12% of cases; so-called spotless RMSF). Therefore, absence of rash should not be a reason to withhold treatment.¹⁶ Empiric treatment with doxycycline should be started promptly for all suspected cases of RMSF because of the rapid progression of disease and an increased risk for morbidity and mortality with delayed diagnosis.

Patients do not become antibody positive until 7 to 10 days after symptoms begin; therefore, treatment should not be delayed while awaiting serologic test results. The case fatality rate in the United States is estimated to be 5% to 10% overall and as high as 40% to 50% among patients who are not treated until day 8 or 9 of illness.¹⁷

Cutaneous complications include skin necrosis and gangrene due to continuous tissue damage in severe cases.¹⁶ Severe infection also may manifest with signs of multiorgan system damage, including altered mental status, cerebral edema, meningismus, transient deafness, myocarditis, pulmonary hemorrhage and edema, conjunctivitis, retinal abnormalities, and acute renal failure.^14,16 Risk factors for more severe illness include delayed treatment, age 40 years or older or younger than 10 years, and underlying medical conditions such as alcoholic liver disease and glucose-6-phosphate dehydrogenase deficiency. However, even some healthy young patients die of this disease.¹⁷

Mediterranean Spotted Fever—Rhipicephalus sanguineus sensu lato is the primary vector of MSF, which is prevalent in areas adjacent to the Mediterranean Sea, including southern Europe, Africa, and Central Asia; Sicily is the most highly affected region.¹⁸ Findings with MSF are nearly identical to those of RMSF, except that tache noire is more common, present in as many as 70% of cases at the site of the inoculating tick bite, and MSF typically follows a less severe clinical course.¹² Similar to other rickettsial diseases, the pathogenesis of MSF involves direct injury to vascular endothelial cells, causing a vasculitis that is responsible for the clinical abnormalities observed.

Patients with severe MSF experience complications similar to severe RMSF, including neurologic manifestations and multiorgan damage.¹⁸ Risk factors include advanced age, immunocompromised state, cardiac disease, chronic alcoholism, diabetes mellitus, glucose-6-phosphate dehydrogenase deficiency, respiratory insufficiency, and delayed treatment.¹⁸

Treatment—For all spotted fever group rickettsial infections, doxycycline is the treatment of choice for all patients, including children and pregnant women. Treatment should be started without delay; recommended dosages are 100 mg twice daily for children weighing more than 45 kg and adults, and 2.2 mg/kg twice daily for children weighing 45 kg or less.¹²

Rhipicephalus tick bites rarely can result in paralysis; however, Dermacentor ticks are responsible for most cases of tick-related paralysis in North America. Other pathogens proven or reputed to be transmitted by Rhipicephalus sanguineus sensu lato with zoonotic potential include but are not limited to Rickettsia massiliae, Coxiella burnetti, Anaplasma platys, Leishmania infantum, and Crimean-Congo hemorrhagic fever virus (Nairovirus).¹⁹

Environmental Treatment and Prevention

The most effective way to prevent tick-borne illness is avoidance of tick bites. Primary prevention methods include vector control, use of repellents (eg, N,N-diethyl-meta-toluamide [DEET]), picaridin, permethrin), avoidance of areas with a high tick burden, use of protective clothing, and detection and removal of ticks as soon as possible.

Environmental and veterinary controls also are important methods of tick-bite prevention. A veterinarian can recommend a variety of agents for dogs and cats that prevent attachment of ticks. Environmental controls include synthetic or natural product-based chemical acaricides and nonchemical methods, such as landscape management (eg, sealing cracks and crevices in homes and controlling tall grasses, weeds, and leaf debris) to minimize potential tick habitat.²⁰ Secondary prevention includes antibiotics for prophylaxis or for treatment of tick-borne disease, when indicated.

Numerous tick repellents are available commercially; others are being studied. DEET, the most widely used topical repellent, has a broad spectrum of activity against many tick species.²¹ In addition, DEET has a well-known safety and toxicity profile, with rare adverse effects, and is safe for use in pregnant women and children older than 2 years. Alternative repellents, such as those containing picaridin, ethyl butylacetylaminopropionate (IR3535 [Merck]), oil of lemon eucalyptus, and 2-undecanone can be effective; some show efficacy comparable to that of DEET.²² Permethrin, a synthetic pyrethroid, is a highly efficacious tick repellent and insecticide, especially when used in conjunction with a topical repellent such as DEET. Unlike topically applied repellents, permethrin spray is applied to fabric (eg, clothing, shoes, bed nets, camping gear), not to skin.

Indiscriminate use of acaricides worldwide has led to increasing selection of acaricide resistance in Rhipicephalus tick species, which is especially true with the use of acaricides in controlling R microplus livestock infestations; several tick populations now show resistance to all major classes of these compounds.^23-25 For that reason, there has been an increasing effort to develop new chemical and nonchemical approaches to tick control that are more environmentally sustainable and strategies to minimize development and progression of resistance such as rotation of acaricides; reducing the frequency of their application; use of pesticide mixtures, synergists, or both; and increasing use of nonacaricidal methods of control.²⁶

Prompt removal of ticks is important for preventing the transmission of tick-borne disease. Proper removal involves rubbing the tick in a circular motion with a moist gauze pad or using fine-tipped tweezers to grasp the tick as close to the skin surface as possible and pulling upward with a steady pressure.^17,27 It is important not to jerk, twist, squeeze, smash, or burn the tick, as this can result in insufficient removal of mouthparts or spread contaminated tick fluids to mucous membranes, increasing the risk for infection. Application of petroleum jelly or nail polish to aid in tick removal have not been shown to be effective and are not recommended.^16,28

Characteristics

Rhipicephalus ticks belong to the Ixodidae family of hard-bodied ticks. They are large and teardrop shaped with an inornate scutum (hard dorsal plate) and relatively short mouthparts attached at a hexagonal basis capitulum (base of the head to which mouthparts are attached)(Figure).¹ Widely spaced eyes and festoons also are present. The first pair of coxae—attachment base for the first pair of legs—are characteristically bifid; males have a pair of sclerotized adanal plates on the ventral surface adjacent to the anus as well as accessory adanal shields.²Rhipicephalus (formerly Boophilus) microplus (the so-called cattle tick) is a newly added species; it lacks posterior festoons, and the anal groove is absent.³

Almost all Rhipicephalus ticks, except for R microplus, are 3-host ticks in which a single blood meal is consumed from a vertebrate host at each active life stage—larva, nymph, and adult—to complete development.^4,5 In contrast to most ixodid ticks, which are exophilic (living outside of human habitation), the Rhipicephalus sanguineus sensu lato species (the brown dog tick) is highly endophilic (adapted to indoor living) and often can be found hidden in cracks and crevices of walls in homes and peridomestic structures.⁶ It is predominately monotropic (all developmental stages feed on the same host species) and has a strong host preference for dogs, though it occasionally feeds on other hosts (eg, humans).⁷ Although most common in tropical and subtropical climates, they can be found anywhere there are dogs due to their ability to colonize indoor dwellings.⁸ In contrast, R microplus ticks have a predilection for cattle and livestock rather than humans, posing a notable concern to livestock worldwide. Infestation results in transmission of disease-causing pathogens, such as Babesia and Anaplasma species, which costs the cattle industry billions of dollars annually.⁹

Clinical Manifestations and Treatment

Tick bites usually manifest as intensely pruritic, erythematous papules at the site of tick attachment due to a local type IV hypersensitivity reaction to antigens in the tick’s saliva. This reaction can be long-lasting. In addition to pruritic papules following a bite, an attached tick can be mistaken for a skin neoplasm or nevus. Given that ticks are small, especially during the larval stage, dermoscopy may be helpful in making a diagnosis.¹⁰ Symptomatic relief usually can be achieved with topical antipruritics or oral antihistamines.

Of public health concern, brown dog ticks are important vectors of Rickettsia rickettsii (the causative organism of Rocky Mountain spotted fever [RMSF]) in the Western hemisphere, and Rickettsia conorii (the causative organism of Mediterranean spotted fever [MSF][also known as Boutonneuse fever]) in the Eastern hemisphere.¹¹ Bites by ticks carrying rickettsial disease classically manifest with early symptoms of fever, headache, and myalgia, followed by a rash or by a localized eschar or tache noire (a black, necrotic, scabbed lesion) that represents direct endothelial invasion and vascular damage by Rickettsia.¹² Rocky Mountain spotted fever and MSF are more prevalent during summer, likely due, in part, to the combination of increased outdoor activity and a higher rate of tick-questing (host-seeking) behavior in warmer climates.^4,7

Rocky Mountain Spotted Fever—Dermacentor variabilis is the primary vector of RMSF in the southeastern United States; Dermacentor andersoni is the major vector of RMSF in Rocky Mountain states. Rhipicephalus sanguineus sensu lato is an important vector of RMSF in the southwestern United States, Mexico, and Central America.^11,13

Early symptoms of RMSF are nonspecific and can include fever, headache, arthralgia, myalgia, and malaise. Gastrointestinal tract symptoms (eg, nausea, vomiting, anorexia) may occur; notable abdominal pain occurs in some patients, particularly children. A characteristic petechial rash occurs in as many as 90% of patients, typically at the third to fifth day of illness, and classically begins on the wrists and ankles, with progression to the palms and soles before spreading centripetally to the arms, legs, and trunk.¹⁴ An eschar at the inoculation site is uncommon in RMSF; when present, it is more suggestive of MSF.¹⁵

The classic triad of fever, headache, and rash is present in 3% of patients during the first 3 days after a tick bite and in 60% to 70% within 2 weeks.¹⁶ A rash often is absent when patients first seek medical attention and may not develop (absent in 9% to 12% of cases; so-called spotless RMSF). Therefore, absence of rash should not be a reason to withhold treatment.¹⁶ Empiric treatment with doxycycline should be started promptly for all suspected cases of RMSF because of the rapid progression of disease and an increased risk for morbidity and mortality with delayed diagnosis.

Patients do not become antibody positive until 7 to 10 days after symptoms begin; therefore, treatment should not be delayed while awaiting serologic test results. The case fatality rate in the United States is estimated to be 5% to 10% overall and as high as 40% to 50% among patients who are not treated until day 8 or 9 of illness.¹⁷

Cutaneous complications include skin necrosis and gangrene due to continuous tissue damage in severe cases.¹⁶ Severe infection also may manifest with signs of multiorgan system damage, including altered mental status, cerebral edema, meningismus, transient deafness, myocarditis, pulmonary hemorrhage and edema, conjunctivitis, retinal abnormalities, and acute renal failure.^14,16 Risk factors for more severe illness include delayed treatment, age 40 years or older or younger than 10 years, and underlying medical conditions such as alcoholic liver disease and glucose-6-phosphate dehydrogenase deficiency. However, even some healthy young patients die of this disease.¹⁷

Mediterranean Spotted Fever—Rhipicephalus sanguineus sensu lato is the primary vector of MSF, which is prevalent in areas adjacent to the Mediterranean Sea, including southern Europe, Africa, and Central Asia; Sicily is the most highly affected region.¹⁸ Findings with MSF are nearly identical to those of RMSF, except that tache noire is more common, present in as many as 70% of cases at the site of the inoculating tick bite, and MSF typically follows a less severe clinical course.¹² Similar to other rickettsial diseases, the pathogenesis of MSF involves direct injury to vascular endothelial cells, causing a vasculitis that is responsible for the clinical abnormalities observed.

Patients with severe MSF experience complications similar to severe RMSF, including neurologic manifestations and multiorgan damage.¹⁸ Risk factors include advanced age, immunocompromised state, cardiac disease, chronic alcoholism, diabetes mellitus, glucose-6-phosphate dehydrogenase deficiency, respiratory insufficiency, and delayed treatment.¹⁸

Treatment—For all spotted fever group rickettsial infections, doxycycline is the treatment of choice for all patients, including children and pregnant women. Treatment should be started without delay; recommended dosages are 100 mg twice daily for children weighing more than 45 kg and adults, and 2.2 mg/kg twice daily for children weighing 45 kg or less.¹²

Rhipicephalus tick bites rarely can result in paralysis; however, Dermacentor ticks are responsible for most cases of tick-related paralysis in North America. Other pathogens proven or reputed to be transmitted by Rhipicephalus sanguineus sensu lato with zoonotic potential include but are not limited to Rickettsia massiliae, Coxiella burnetti, Anaplasma platys, Leishmania infantum, and Crimean-Congo hemorrhagic fever virus (Nairovirus).¹⁹

Environmental Treatment and Prevention

The most effective way to prevent tick-borne illness is avoidance of tick bites. Primary prevention methods include vector control, use of repellents (eg, N,N-diethyl-meta-toluamide [DEET]), picaridin, permethrin), avoidance of areas with a high tick burden, use of protective clothing, and detection and removal of ticks as soon as possible.

Environmental and veterinary controls also are important methods of tick-bite prevention. A veterinarian can recommend a variety of agents for dogs and cats that prevent attachment of ticks. Environmental controls include synthetic or natural product-based chemical acaricides and nonchemical methods, such as landscape management (eg, sealing cracks and crevices in homes and controlling tall grasses, weeds, and leaf debris) to minimize potential tick habitat.²⁰ Secondary prevention includes antibiotics for prophylaxis or for treatment of tick-borne disease, when indicated.

Numerous tick repellents are available commercially; others are being studied. DEET, the most widely used topical repellent, has a broad spectrum of activity against many tick species.²¹ In addition, DEET has a well-known safety and toxicity profile, with rare adverse effects, and is safe for use in pregnant women and children older than 2 years. Alternative repellents, such as those containing picaridin, ethyl butylacetylaminopropionate (IR3535 [Merck]), oil of lemon eucalyptus, and 2-undecanone can be effective; some show efficacy comparable to that of DEET.²² Permethrin, a synthetic pyrethroid, is a highly efficacious tick repellent and insecticide, especially when used in conjunction with a topical repellent such as DEET. Unlike topically applied repellents, permethrin spray is applied to fabric (eg, clothing, shoes, bed nets, camping gear), not to skin.

Indiscriminate use of acaricides worldwide has led to increasing selection of acaricide resistance in Rhipicephalus tick species, which is especially true with the use of acaricides in controlling R microplus livestock infestations; several tick populations now show resistance to all major classes of these compounds.^23-25 For that reason, there has been an increasing effort to develop new chemical and nonchemical approaches to tick control that are more environmentally sustainable and strategies to minimize development and progression of resistance such as rotation of acaricides; reducing the frequency of their application; use of pesticide mixtures, synergists, or both; and increasing use of nonacaricidal methods of control.²⁶

Prompt removal of ticks is important for preventing the transmission of tick-borne disease. Proper removal involves rubbing the tick in a circular motion with a moist gauze pad or using fine-tipped tweezers to grasp the tick as close to the skin surface as possible and pulling upward with a steady pressure.^17,27 It is important not to jerk, twist, squeeze, smash, or burn the tick, as this can result in insufficient removal of mouthparts or spread contaminated tick fluids to mucous membranes, increasing the risk for infection. Application of petroleum jelly or nail polish to aid in tick removal have not been shown to be effective and are not recommended.^16,28

Amid the current wave of winter respiratory virus cases, influenza (types A and B) leads the way with the highest number of emergency room visits, followed closely by COVID-19, thanks to the JN.1 variant, and respiratory syncytial virus (RSV). With various similarities and differences in disease presentations, how challenging is it for physician’s to distinguish between, diagnose, and treat COVID-19 vs RSV and influenza? 

While these three respiratory viruses often have similar presentations, you may often find that patients with COVID-19 experience more fever, dry cough, and labored breathing, according to Cyrus Munguti, MD, assistant professor of medicine at KU Medical Center and hospitalist at Wesley Medical Center, Wichita, Kansas. 

“COVID-19 patients tend to have trouble breathing because the alveoli are affected and get inflammation and fluid accumulating in the lungs, and they end up having little to no oxygen,” said Dr. Munguti. “When we check their vital signs, patients with COVID tend to have hypoxemia [meaning saturations are less than 88% or 90% depending on the guidelines you follow].”

Patients with RSV and influenza tend to have more upper respiratory symptoms, like runny nose, sternutation — which later can progress to a cough in the upper airways, Dr. Munguti said. Unlike with COVID-19, patients with RSV and influenza — generally until they are very sick — often do not experience hypoxemia.

Inflammation in the airways can form as a result of all three viruses. Furthermore, bacteria that live in these airways could lead to a secondary bacterial infection in the upper respiratory and lower respiratory tracts — which could then cause pneumonia, Dr. Munguti said.

Another note: Changes in COVID-19 variants over the years have made it increasingly difficult to differentiate COVID-19 symptoms from those of RSV and influenza, according to Panagis Galiatsatos, MD, pulmonologist and associate professor at Johns Hopkins Medicine. “The Alpha through Delta variants really were a lot more lung tissue invading,” Dr. Galiatsatos said. “With the COVID-19 Omicron family — its capabilities are similar to what flu and RSV have done over the years. It’s more airway-invading.”

It’s critical to understand that diagnosing these diseases based on symptoms alone can be quite fickle, according to Dr. Galiatsatos. Objective tests, either at home or in a laboratory, are preferred. This is largely because disease presentation can depend on the host factor that the virus enters into, said Dr. Galiatsatos. For example, virus symptoms may look different for a patient with asthma and for someone with heart disease.

With children being among the most vulnerable for severe respiratory illness, testing and treatment are paramount and can be quite accurate in seasons where respiratory viruses thrive, according to Stan Spinner, MD, chief medical officer at Texas Children’s Pediatrics and Urgent Care. “When individuals are tested for either of these conditions when the prevalence in the community is low, we tend to see false positive results.” 

Texas Children’s Pediatrics and Urgent Care’s 12 sites offer COVID-19 and influenza antigen tests that have results ready in around 10 minutes. RSV testing, on the other hand, is limited to around half of the Texas Children’s Pediatrics and none of the urgent care locations, as the test can only be administered through a nasal swab conducted by a physician. As there is no specific treatment or therapy for RSV, the benefits of RSV testing can actually be quite low — often leading to frustrated parents regarding next steps after diagnosis.

“There are a number of respiratory viruses that may present with similar symptoms as RSV, and some of these viruses may even lead to much of the same adverse outcomes as the RSV virus,” Dr. Galiatsatos said. “Consequently, our physicians need to help parents understand this and give them guidance as to when to seek medical attention for worsening symptoms.”

There are two new RSV immunizations to treat certain demographics of patients, Dr. Spinner added. One is an RSV vaccine for infants under 8 months old, though there is limited supply. There is also an RSV vaccine available for pregnant women (between 32 and 36 weeks gestation) that has proved to be effective in fending off RSV infections in newborns up to 6 months old. 

Physicians should remain diligent in stressing to patients that vaccinations against COVID-19 and influenza play a key role in keeping their families safe during seasons of staggering respiratory infections.

“These vaccines are extremely safe, and while they may not always prevent infection, these vaccines are extremely effective in preventing more serious consequences, such as hospitalization or death,” Dr. Galiatsatos said.
 

A version of this article appeared on Medscape.com.

Amid the current wave of winter respiratory virus cases, influenza (types A and B) leads the way with the highest number of emergency room visits, followed closely by COVID-19, thanks to the JN.1 variant, and respiratory syncytial virus (RSV). With various similarities and differences in disease presentations, how challenging is it for physician’s to distinguish between, diagnose, and treat COVID-19 vs RSV and influenza? 

While these three respiratory viruses often have similar presentations, you may often find that patients with COVID-19 experience more fever, dry cough, and labored breathing, according to Cyrus Munguti, MD, assistant professor of medicine at KU Medical Center and hospitalist at Wesley Medical Center, Wichita, Kansas. 

“COVID-19 patients tend to have trouble breathing because the alveoli are affected and get inflammation and fluid accumulating in the lungs, and they end up having little to no oxygen,” said Dr. Munguti. “When we check their vital signs, patients with COVID tend to have hypoxemia [meaning saturations are less than 88% or 90% depending on the guidelines you follow].”

Patients with RSV and influenza tend to have more upper respiratory symptoms, like runny nose, sternutation — which later can progress to a cough in the upper airways, Dr. Munguti said. Unlike with COVID-19, patients with RSV and influenza — generally until they are very sick — often do not experience hypoxemia.

Inflammation in the airways can form as a result of all three viruses. Furthermore, bacteria that live in these airways could lead to a secondary bacterial infection in the upper respiratory and lower respiratory tracts — which could then cause pneumonia, Dr. Munguti said.

Another note: Changes in COVID-19 variants over the years have made it increasingly difficult to differentiate COVID-19 symptoms from those of RSV and influenza, according to Panagis Galiatsatos, MD, pulmonologist and associate professor at Johns Hopkins Medicine. “The Alpha through Delta variants really were a lot more lung tissue invading,” Dr. Galiatsatos said. “With the COVID-19 Omicron family — its capabilities are similar to what flu and RSV have done over the years. It’s more airway-invading.”

It’s critical to understand that diagnosing these diseases based on symptoms alone can be quite fickle, according to Dr. Galiatsatos. Objective tests, either at home or in a laboratory, are preferred. This is largely because disease presentation can depend on the host factor that the virus enters into, said Dr. Galiatsatos. For example, virus symptoms may look different for a patient with asthma and for someone with heart disease.

With children being among the most vulnerable for severe respiratory illness, testing and treatment are paramount and can be quite accurate in seasons where respiratory viruses thrive, according to Stan Spinner, MD, chief medical officer at Texas Children’s Pediatrics and Urgent Care. “When individuals are tested for either of these conditions when the prevalence in the community is low, we tend to see false positive results.” 

Texas Children’s Pediatrics and Urgent Care’s 12 sites offer COVID-19 and influenza antigen tests that have results ready in around 10 minutes. RSV testing, on the other hand, is limited to around half of the Texas Children’s Pediatrics and none of the urgent care locations, as the test can only be administered through a nasal swab conducted by a physician. As there is no specific treatment or therapy for RSV, the benefits of RSV testing can actually be quite low — often leading to frustrated parents regarding next steps after diagnosis.

“There are a number of respiratory viruses that may present with similar symptoms as RSV, and some of these viruses may even lead to much of the same adverse outcomes as the RSV virus,” Dr. Galiatsatos said. “Consequently, our physicians need to help parents understand this and give them guidance as to when to seek medical attention for worsening symptoms.”

There are two new RSV immunizations to treat certain demographics of patients, Dr. Spinner added. One is an RSV vaccine for infants under 8 months old, though there is limited supply. There is also an RSV vaccine available for pregnant women (between 32 and 36 weeks gestation) that has proved to be effective in fending off RSV infections in newborns up to 6 months old. 

Physicians should remain diligent in stressing to patients that vaccinations against COVID-19 and influenza play a key role in keeping their families safe during seasons of staggering respiratory infections.

“These vaccines are extremely safe, and while they may not always prevent infection, these vaccines are extremely effective in preventing more serious consequences, such as hospitalization or death,” Dr. Galiatsatos said.
 

A version of this article appeared on Medscape.com.

Amid the current wave of winter respiratory virus cases, influenza (types A and B) leads the way with the highest number of emergency room visits, followed closely by COVID-19, thanks to the JN.1 variant, and respiratory syncytial virus (RSV). With various similarities and differences in disease presentations, how challenging is it for physician’s to distinguish between, diagnose, and treat COVID-19 vs RSV and influenza? 

While these three respiratory viruses often have similar presentations, you may often find that patients with COVID-19 experience more fever, dry cough, and labored breathing, according to Cyrus Munguti, MD, assistant professor of medicine at KU Medical Center and hospitalist at Wesley Medical Center, Wichita, Kansas. 

“COVID-19 patients tend to have trouble breathing because the alveoli are affected and get inflammation and fluid accumulating in the lungs, and they end up having little to no oxygen,” said Dr. Munguti. “When we check their vital signs, patients with COVID tend to have hypoxemia [meaning saturations are less than 88% or 90% depending on the guidelines you follow].”

Patients with RSV and influenza tend to have more upper respiratory symptoms, like runny nose, sternutation — which later can progress to a cough in the upper airways, Dr. Munguti said. Unlike with COVID-19, patients with RSV and influenza — generally until they are very sick — often do not experience hypoxemia.

Inflammation in the airways can form as a result of all three viruses. Furthermore, bacteria that live in these airways could lead to a secondary bacterial infection in the upper respiratory and lower respiratory tracts — which could then cause pneumonia, Dr. Munguti said.

Another note: Changes in COVID-19 variants over the years have made it increasingly difficult to differentiate COVID-19 symptoms from those of RSV and influenza, according to Panagis Galiatsatos, MD, pulmonologist and associate professor at Johns Hopkins Medicine. “The Alpha through Delta variants really were a lot more lung tissue invading,” Dr. Galiatsatos said. “With the COVID-19 Omicron family — its capabilities are similar to what flu and RSV have done over the years. It’s more airway-invading.”

It’s critical to understand that diagnosing these diseases based on symptoms alone can be quite fickle, according to Dr. Galiatsatos. Objective tests, either at home or in a laboratory, are preferred. This is largely because disease presentation can depend on the host factor that the virus enters into, said Dr. Galiatsatos. For example, virus symptoms may look different for a patient with asthma and for someone with heart disease.

With children being among the most vulnerable for severe respiratory illness, testing and treatment are paramount and can be quite accurate in seasons where respiratory viruses thrive, according to Stan Spinner, MD, chief medical officer at Texas Children’s Pediatrics and Urgent Care. “When individuals are tested for either of these conditions when the prevalence in the community is low, we tend to see false positive results.” 

Texas Children’s Pediatrics and Urgent Care’s 12 sites offer COVID-19 and influenza antigen tests that have results ready in around 10 minutes. RSV testing, on the other hand, is limited to around half of the Texas Children’s Pediatrics and none of the urgent care locations, as the test can only be administered through a nasal swab conducted by a physician. As there is no specific treatment or therapy for RSV, the benefits of RSV testing can actually be quite low — often leading to frustrated parents regarding next steps after diagnosis.

“There are a number of respiratory viruses that may present with similar symptoms as RSV, and some of these viruses may even lead to much of the same adverse outcomes as the RSV virus,” Dr. Galiatsatos said. “Consequently, our physicians need to help parents understand this and give them guidance as to when to seek medical attention for worsening symptoms.”

There are two new RSV immunizations to treat certain demographics of patients, Dr. Spinner added. One is an RSV vaccine for infants under 8 months old, though there is limited supply. There is also an RSV vaccine available for pregnant women (between 32 and 36 weeks gestation) that has proved to be effective in fending off RSV infections in newborns up to 6 months old. 

Physicians should remain diligent in stressing to patients that vaccinations against COVID-19 and influenza play a key role in keeping their families safe during seasons of staggering respiratory infections.

“These vaccines are extremely safe, and while they may not always prevent infection, these vaccines are extremely effective in preventing more serious consequences, such as hospitalization or death,” Dr. Galiatsatos said.
 

A version of this article appeared on Medscape.com.

When infants are born, they have nearly a clean slate with regard to their immune systems. Virtually all their immune cells are naive. They have no immunity memory. Vaccines at birth, and in the first 2 years of life, elicit variable antibody levels and cellular immune responses. Sometimes, this leaves fully vaccinated children unprotected against vaccine-preventable infectious diseases.

Newborns are bombarded at birth with microbes and other antigenic stimuli from the environment; food in the form of breast milk, formula, water; and vaccines, such as hepatitis B and, in other countries, with BCG. At birth, to avoid immunologically-induced injury, immune responses favor immunologic tolerance. However, adaptation must be rapid to avoid life-threatening infections. To navigate the gauntlet of microbe and environmental exposures and vaccines, the neonatal immune system moves through a gradual maturation process toward immune responsivity. The maturation occurs at different rates in different children. A major factor affecting immune development is the microbiome of the newborn and the first 100 days of life.
 

Reassessing Vaccine Responsiveness

Vaccine responsiveness is usually assessed by measuring antibody levels in blood. Until recently, it was thought to be “bad luck” when a child failed to develop protective immunity following vaccination. The bad luck was suggested to involve illness at the time of vaccination, especially illness occurring with fever, and especially common viral infections. But studies proved that notion incorrect. About 10 years ago I became more interested in variability in vaccine responses in the first 2 years of life. In 2016, my laboratory described a specific population of children with specific cellular immune deficiencies that we classified as low vaccine responders (LVRs).¹ To preclude the suggestion that low vaccine responses were to be considered normal biological variation, we chose an a priori definition of LVR as those with sub-protective IgG antibody levels to four (≥ 66 %) of six tested vaccines in DTaP-Hib (diphtheria toxoid, tetanus toxoid, pertussis toxoid, pertactin, and filamentous hemagglutinin [DTaP] and Haemophilus influenzae type b polysaccharide capsule [Hib]). Antibody levels were measured at 1 year of age following primary vaccinations at child age 2, 4, and 6 months old. The remaining 89% of children we termed normal vaccine responders (NVRs). We additionally tested antibody responses to viral protein and pneumococcal polysaccharide conjugated antigens (polio serotypes 1, 2, and 3, hepatitis B, and Streptococcus pneumoniae capsular polysaccharides serotypes 6B, 14, and 23F). Responses to these vaccine antigens were similar to the six vaccines (DTaP/Hib) used to define LVR. We and other groups have used alternative definitions of low vaccine responses that rely on statistics.

I recently reviewed the topic of the determinants of vaccine responses in early life, with a focus on the infant microbiome and metabolome: a.) cesarean section versus vaginal delivery, b.) breast versus formula feeding and c.) antibiotic exposure, that impact the immune response² (Figure). In the review I also discussed how microbiome may serve as natural adjuvants for vaccine responses, how microbiota-derived metabolites influence vaccine responses, and how low vaccine responses in early life may be linked to increased infection susceptibility (Figure).

Courtesy Dr. Pichichero

Multiple studies strongly support the notion that breastfeeding has a favorable impact on immune development in early life associated with better vaccine responses, mediated by the microbiome. The mechanism of favorable immune responses to vaccines largely relates to the presence of a specific bacteria species, Bifidobacterium infantis. Breast milk contains human milk oligosaccharides that are not digestible by newborns. B. infantis is a strain of bacteria that utilizes these non-digestible oligosaccharides. Thereby, infants fed breast milk provides B. infantis the essential source of nutrition for its growth and predominance in the newborn gut. Studies have shown that Bifidobacterium spp. abundance in early life is correlated with better immune responses to multiple vaccines. Bifidobacterium spp. abundance has been positively correlated with antibody responses measured after 2 years, linking the microbiome composition to the durability of vaccine-induced immune responses.

Antibiotic exposure in early life may disproportionately damage the newborn and infant microbiome compared with later childhood. The average child receives about three antibiotic courses by the age of 2 years. My lab was among the first to describe the adverse effects of antibiotics on vaccine responses in early life.³ We found that broader spectrum antibiotics had a greater adverse effect on vaccine-induced antibody levels than narrower spectrum antibiotics. Ten-day versus five-day treatment courses had a greater negative effect. Multiple antibiotic courses over time (cumulative antibiotic exposure) was negatively associated with vaccine-induced antibody levels.

Over 11 % of live births worldwide occur preterm. Because bacterial infections are frequent complications of preterm birth, 79 % of very low birthweight and 87 % of extremely low birthweight infants in US NICUs receive antibiotics within 3 days of birth. Recently, my group studied full-term infants at birth and found that exposure to parenteral antibiotics at birth or during the first days of life had an adverse effect on vaccine responses.⁴
 

Microbiome Impacts Immunity

How does the microbiome affect immunity, and specifically vaccine responses? Microbial-derived metabolites affect host immunity. Gut bacteria produce short chain fatty acids (SCFAs: acetate, propionate, butyrate) [115]. SCFAs positively influence immunity cells. Vitamin D metabolites are generated by intestinal bacteria and those metabolites positively influence immunity. Secondary bile acids produced by Clostridium spp. are involved in favorable immune responses. Increased levels of phenylpyruvic acid produced by gut and/or nasopharyngeal microbiota correlate with reduced vaccine responses and upregulated metabolome genes that encode for oxidative phosphorylation correlate with increased vaccine responses.

In summary, immune development commences at birth. Impairment in responses to vaccination in children have been linked to disturbance in the microbiome. Cesarean section and absence of breastfeeding are associated with adverse microbiota composition. Antibiotics perturb healthy microbiota development. The microbiota affect immunity in several ways, among them are effects by metabolites generated by the commensals that inhabit the child host. A child who responds poorly to vaccines and has specific immune cell dysfunction caused by problems with the microbiome also displays increased infection proneness. But that is a story for another column, later.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Pichichero ME et al. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.

2. Pichichero ME. Cell Immunol. 2023 Nov-Dec:393-394:104777. doi: 10.1016/j.cellimm.2023.104777.

3. Chapman TJ et al. Pediatrics. 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

4. Shaffer M et al. mSystems. 2023 Oct 26;8(5):e0066123. doi: 10.1128/msystems.00661-23.

When infants are born, they have nearly a clean slate with regard to their immune systems. Virtually all their immune cells are naive. They have no immunity memory. Vaccines at birth, and in the first 2 years of life, elicit variable antibody levels and cellular immune responses. Sometimes, this leaves fully vaccinated children unprotected against vaccine-preventable infectious diseases.

Newborns are bombarded at birth with microbes and other antigenic stimuli from the environment; food in the form of breast milk, formula, water; and vaccines, such as hepatitis B and, in other countries, with BCG. At birth, to avoid immunologically-induced injury, immune responses favor immunologic tolerance. However, adaptation must be rapid to avoid life-threatening infections. To navigate the gauntlet of microbe and environmental exposures and vaccines, the neonatal immune system moves through a gradual maturation process toward immune responsivity. The maturation occurs at different rates in different children. A major factor affecting immune development is the microbiome of the newborn and the first 100 days of life.
 

Reassessing Vaccine Responsiveness

Vaccine responsiveness is usually assessed by measuring antibody levels in blood. Until recently, it was thought to be “bad luck” when a child failed to develop protective immunity following vaccination. The bad luck was suggested to involve illness at the time of vaccination, especially illness occurring with fever, and especially common viral infections. But studies proved that notion incorrect. About 10 years ago I became more interested in variability in vaccine responses in the first 2 years of life. In 2016, my laboratory described a specific population of children with specific cellular immune deficiencies that we classified as low vaccine responders (LVRs).¹ To preclude the suggestion that low vaccine responses were to be considered normal biological variation, we chose an a priori definition of LVR as those with sub-protective IgG antibody levels to four (≥ 66 %) of six tested vaccines in DTaP-Hib (diphtheria toxoid, tetanus toxoid, pertussis toxoid, pertactin, and filamentous hemagglutinin [DTaP] and Haemophilus influenzae type b polysaccharide capsule [Hib]). Antibody levels were measured at 1 year of age following primary vaccinations at child age 2, 4, and 6 months old. The remaining 89% of children we termed normal vaccine responders (NVRs). We additionally tested antibody responses to viral protein and pneumococcal polysaccharide conjugated antigens (polio serotypes 1, 2, and 3, hepatitis B, and Streptococcus pneumoniae capsular polysaccharides serotypes 6B, 14, and 23F). Responses to these vaccine antigens were similar to the six vaccines (DTaP/Hib) used to define LVR. We and other groups have used alternative definitions of low vaccine responses that rely on statistics.

I recently reviewed the topic of the determinants of vaccine responses in early life, with a focus on the infant microbiome and metabolome: a.) cesarean section versus vaginal delivery, b.) breast versus formula feeding and c.) antibiotic exposure, that impact the immune response² (Figure). In the review I also discussed how microbiome may serve as natural adjuvants for vaccine responses, how microbiota-derived metabolites influence vaccine responses, and how low vaccine responses in early life may be linked to increased infection susceptibility (Figure).

Courtesy Dr. Pichichero

Multiple studies strongly support the notion that breastfeeding has a favorable impact on immune development in early life associated with better vaccine responses, mediated by the microbiome. The mechanism of favorable immune responses to vaccines largely relates to the presence of a specific bacteria species, Bifidobacterium infantis. Breast milk contains human milk oligosaccharides that are not digestible by newborns. B. infantis is a strain of bacteria that utilizes these non-digestible oligosaccharides. Thereby, infants fed breast milk provides B. infantis the essential source of nutrition for its growth and predominance in the newborn gut. Studies have shown that Bifidobacterium spp. abundance in early life is correlated with better immune responses to multiple vaccines. Bifidobacterium spp. abundance has been positively correlated with antibody responses measured after 2 years, linking the microbiome composition to the durability of vaccine-induced immune responses.

Antibiotic exposure in early life may disproportionately damage the newborn and infant microbiome compared with later childhood. The average child receives about three antibiotic courses by the age of 2 years. My lab was among the first to describe the adverse effects of antibiotics on vaccine responses in early life.³ We found that broader spectrum antibiotics had a greater adverse effect on vaccine-induced antibody levels than narrower spectrum antibiotics. Ten-day versus five-day treatment courses had a greater negative effect. Multiple antibiotic courses over time (cumulative antibiotic exposure) was negatively associated with vaccine-induced antibody levels.

Over 11 % of live births worldwide occur preterm. Because bacterial infections are frequent complications of preterm birth, 79 % of very low birthweight and 87 % of extremely low birthweight infants in US NICUs receive antibiotics within 3 days of birth. Recently, my group studied full-term infants at birth and found that exposure to parenteral antibiotics at birth or during the first days of life had an adverse effect on vaccine responses.⁴
 

Microbiome Impacts Immunity

How does the microbiome affect immunity, and specifically vaccine responses? Microbial-derived metabolites affect host immunity. Gut bacteria produce short chain fatty acids (SCFAs: acetate, propionate, butyrate) [115]. SCFAs positively influence immunity cells. Vitamin D metabolites are generated by intestinal bacteria and those metabolites positively influence immunity. Secondary bile acids produced by Clostridium spp. are involved in favorable immune responses. Increased levels of phenylpyruvic acid produced by gut and/or nasopharyngeal microbiota correlate with reduced vaccine responses and upregulated metabolome genes that encode for oxidative phosphorylation correlate with increased vaccine responses.

In summary, immune development commences at birth. Impairment in responses to vaccination in children have been linked to disturbance in the microbiome. Cesarean section and absence of breastfeeding are associated with adverse microbiota composition. Antibiotics perturb healthy microbiota development. The microbiota affect immunity in several ways, among them are effects by metabolites generated by the commensals that inhabit the child host. A child who responds poorly to vaccines and has specific immune cell dysfunction caused by problems with the microbiome also displays increased infection proneness. But that is a story for another column, later.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Pichichero ME et al. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.

2. Pichichero ME. Cell Immunol. 2023 Nov-Dec:393-394:104777. doi: 10.1016/j.cellimm.2023.104777.

3. Chapman TJ et al. Pediatrics. 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

4. Shaffer M et al. mSystems. 2023 Oct 26;8(5):e0066123. doi: 10.1128/msystems.00661-23.

When infants are born, they have nearly a clean slate with regard to their immune systems. Virtually all their immune cells are naive. They have no immunity memory. Vaccines at birth, and in the first 2 years of life, elicit variable antibody levels and cellular immune responses. Sometimes, this leaves fully vaccinated children unprotected against vaccine-preventable infectious diseases.

Newborns are bombarded at birth with microbes and other antigenic stimuli from the environment; food in the form of breast milk, formula, water; and vaccines, such as hepatitis B and, in other countries, with BCG. At birth, to avoid immunologically-induced injury, immune responses favor immunologic tolerance. However, adaptation must be rapid to avoid life-threatening infections. To navigate the gauntlet of microbe and environmental exposures and vaccines, the neonatal immune system moves through a gradual maturation process toward immune responsivity. The maturation occurs at different rates in different children. A major factor affecting immune development is the microbiome of the newborn and the first 100 days of life.
 

Reassessing Vaccine Responsiveness

Vaccine responsiveness is usually assessed by measuring antibody levels in blood. Until recently, it was thought to be “bad luck” when a child failed to develop protective immunity following vaccination. The bad luck was suggested to involve illness at the time of vaccination, especially illness occurring with fever, and especially common viral infections. But studies proved that notion incorrect. About 10 years ago I became more interested in variability in vaccine responses in the first 2 years of life. In 2016, my laboratory described a specific population of children with specific cellular immune deficiencies that we classified as low vaccine responders (LVRs).¹ To preclude the suggestion that low vaccine responses were to be considered normal biological variation, we chose an a priori definition of LVR as those with sub-protective IgG antibody levels to four (≥ 66 %) of six tested vaccines in DTaP-Hib (diphtheria toxoid, tetanus toxoid, pertussis toxoid, pertactin, and filamentous hemagglutinin [DTaP] and Haemophilus influenzae type b polysaccharide capsule [Hib]). Antibody levels were measured at 1 year of age following primary vaccinations at child age 2, 4, and 6 months old. The remaining 89% of children we termed normal vaccine responders (NVRs). We additionally tested antibody responses to viral protein and pneumococcal polysaccharide conjugated antigens (polio serotypes 1, 2, and 3, hepatitis B, and Streptococcus pneumoniae capsular polysaccharides serotypes 6B, 14, and 23F). Responses to these vaccine antigens were similar to the six vaccines (DTaP/Hib) used to define LVR. We and other groups have used alternative definitions of low vaccine responses that rely on statistics.

I recently reviewed the topic of the determinants of vaccine responses in early life, with a focus on the infant microbiome and metabolome: a.) cesarean section versus vaginal delivery, b.) breast versus formula feeding and c.) antibiotic exposure, that impact the immune response² (Figure). In the review I also discussed how microbiome may serve as natural adjuvants for vaccine responses, how microbiota-derived metabolites influence vaccine responses, and how low vaccine responses in early life may be linked to increased infection susceptibility (Figure).

Courtesy Dr. Pichichero

Multiple studies strongly support the notion that breastfeeding has a favorable impact on immune development in early life associated with better vaccine responses, mediated by the microbiome. The mechanism of favorable immune responses to vaccines largely relates to the presence of a specific bacteria species, Bifidobacterium infantis. Breast milk contains human milk oligosaccharides that are not digestible by newborns. B. infantis is a strain of bacteria that utilizes these non-digestible oligosaccharides. Thereby, infants fed breast milk provides B. infantis the essential source of nutrition for its growth and predominance in the newborn gut. Studies have shown that Bifidobacterium spp. abundance in early life is correlated with better immune responses to multiple vaccines. Bifidobacterium spp. abundance has been positively correlated with antibody responses measured after 2 years, linking the microbiome composition to the durability of vaccine-induced immune responses.

Antibiotic exposure in early life may disproportionately damage the newborn and infant microbiome compared with later childhood. The average child receives about three antibiotic courses by the age of 2 years. My lab was among the first to describe the adverse effects of antibiotics on vaccine responses in early life.³ We found that broader spectrum antibiotics had a greater adverse effect on vaccine-induced antibody levels than narrower spectrum antibiotics. Ten-day versus five-day treatment courses had a greater negative effect. Multiple antibiotic courses over time (cumulative antibiotic exposure) was negatively associated with vaccine-induced antibody levels.

Over 11 % of live births worldwide occur preterm. Because bacterial infections are frequent complications of preterm birth, 79 % of very low birthweight and 87 % of extremely low birthweight infants in US NICUs receive antibiotics within 3 days of birth. Recently, my group studied full-term infants at birth and found that exposure to parenteral antibiotics at birth or during the first days of life had an adverse effect on vaccine responses.⁴
 

Microbiome Impacts Immunity

How does the microbiome affect immunity, and specifically vaccine responses? Microbial-derived metabolites affect host immunity. Gut bacteria produce short chain fatty acids (SCFAs: acetate, propionate, butyrate) [115]. SCFAs positively influence immunity cells. Vitamin D metabolites are generated by intestinal bacteria and those metabolites positively influence immunity. Secondary bile acids produced by Clostridium spp. are involved in favorable immune responses. Increased levels of phenylpyruvic acid produced by gut and/or nasopharyngeal microbiota correlate with reduced vaccine responses and upregulated metabolome genes that encode for oxidative phosphorylation correlate with increased vaccine responses.

In summary, immune development commences at birth. Impairment in responses to vaccination in children have been linked to disturbance in the microbiome. Cesarean section and absence of breastfeeding are associated with adverse microbiota composition. Antibiotics perturb healthy microbiota development. The microbiota affect immunity in several ways, among them are effects by metabolites generated by the commensals that inhabit the child host. A child who responds poorly to vaccines and has specific immune cell dysfunction caused by problems with the microbiome also displays increased infection proneness. But that is a story for another column, later.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Pichichero ME et al. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.

2. Pichichero ME. Cell Immunol. 2023 Nov-Dec:393-394:104777. doi: 10.1016/j.cellimm.2023.104777.

3. Chapman TJ et al. Pediatrics. 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

4. Shaffer M et al. mSystems. 2023 Oct 26;8(5):e0066123. doi: 10.1128/msystems.00661-23.

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.