Infectious Diseases

Health officials are warning that an increase in the drug-resistant form of the bacteria Shigella is a “serious public health threat.”

The CDC issued the warning Feb. 24 about the rise in the problematic infections. Most of them have been seen in men who have sex with men, but a small number have also occurred in women and in young children.

The bacteria can be spread in a variety of ways, including changing the diaper of an infected baby, touching your mouth when the bacteria are on your hands, eating or drinking contaminated food or water, or through sexual contact. It’s easily transmitted because just a tiny amount of the bacteria is enough to make someone sick.

Shigella infection causes diarrhea that can be bloody. Other symptoms are a fever, belly cramping, and the feeling that you have to poop but your bowels are already empty. Most people recover on their own with rest and fluids, and severe cases can need antibiotic treatment. But strains of the bacteria that are resistant to treatment are on the rise.

Between 2015 and 2022, cases of antibiotic-resistant Shigella infection rose from 0% to 5% of all Shigella cases in the United States. One analysis showed that 82% of cases were in men, 13% in women, and 5% in children. A small sample of affected people provided information about their sexual activity, and 88% of them reported male-to-male sexual contact.

People at increased risk of infections are young children, people who are homeless, international travelers, people who have weakened immune systems, people living with HIV, and men who have sex with men.

The CDC asked health care workers to be on the lookout for these infections and report them.

A version of this article first appeared on WebMD.com.

Health officials are warning that an increase in the drug-resistant form of the bacteria Shigella is a “serious public health threat.”

The CDC issued the warning Feb. 24 about the rise in the problematic infections. Most of them have been seen in men who have sex with men, but a small number have also occurred in women and in young children.

The bacteria can be spread in a variety of ways, including changing the diaper of an infected baby, touching your mouth when the bacteria are on your hands, eating or drinking contaminated food or water, or through sexual contact. It’s easily transmitted because just a tiny amount of the bacteria is enough to make someone sick.

Shigella infection causes diarrhea that can be bloody. Other symptoms are a fever, belly cramping, and the feeling that you have to poop but your bowels are already empty. Most people recover on their own with rest and fluids, and severe cases can need antibiotic treatment. But strains of the bacteria that are resistant to treatment are on the rise.

Between 2015 and 2022, cases of antibiotic-resistant Shigella infection rose from 0% to 5% of all Shigella cases in the United States. One analysis showed that 82% of cases were in men, 13% in women, and 5% in children. A small sample of affected people provided information about their sexual activity, and 88% of them reported male-to-male sexual contact.

People at increased risk of infections are young children, people who are homeless, international travelers, people who have weakened immune systems, people living with HIV, and men who have sex with men.

The CDC asked health care workers to be on the lookout for these infections and report them.

A version of this article first appeared on WebMD.com.

Health officials are warning that an increase in the drug-resistant form of the bacteria Shigella is a “serious public health threat.”

The CDC issued the warning Feb. 24 about the rise in the problematic infections. Most of them have been seen in men who have sex with men, but a small number have also occurred in women and in young children.

The bacteria can be spread in a variety of ways, including changing the diaper of an infected baby, touching your mouth when the bacteria are on your hands, eating or drinking contaminated food or water, or through sexual contact. It’s easily transmitted because just a tiny amount of the bacteria is enough to make someone sick.

Shigella infection causes diarrhea that can be bloody. Other symptoms are a fever, belly cramping, and the feeling that you have to poop but your bowels are already empty. Most people recover on their own with rest and fluids, and severe cases can need antibiotic treatment. But strains of the bacteria that are resistant to treatment are on the rise.

Between 2015 and 2022, cases of antibiotic-resistant Shigella infection rose from 0% to 5% of all Shigella cases in the United States. One analysis showed that 82% of cases were in men, 13% in women, and 5% in children. A small sample of affected people provided information about their sexual activity, and 88% of them reported male-to-male sexual contact.

People at increased risk of infections are young children, people who are homeless, international travelers, people who have weakened immune systems, people living with HIV, and men who have sex with men.

The CDC asked health care workers to be on the lookout for these infections and report them.

A version of this article first appeared on WebMD.com.

The Diagnosis: Plasmablastic Lymphoma

A punch biopsy of one of the leg nodules with hematoxylin and eosin staining revealed sheets of medium to large cells with plasmacytic differentiation (Figure, A and B). Immunohistochemistry showed CD79, epithelial membrane antigen, multiple myeloma 1, and CD138 positivity, as well as CD-19 negativity and positive staining on Epstein-Barr virus (EBV) in situ hybridization (Figure, C). Ki-67 stained greater than 90% of the neoplastic cells. Neoplastic cells were found to be λ restricted on κ and λ immunohistochemistry. Human herpesvirus 8 (HHV-8), CD3, and CD20 stains were negative. Subsequent fluorescent in situ hybridization was positive for MYC/immunoglobulin heavy chain (MYC/IGH) rearrangement t(8;14), confirming a diagnosis of plasmablastic lymphoma (PBL).

A bone marrow biopsy revealed normocellular bone marrow with trilineage hematopoiesis and no morphologic, immunophenotypic, or fluorescent in situ hybridization evidence of plasmablastic lymphoma or other pathology in the bone marrow. Our patient was started on hyper-CVAD (cyclophosphamide, vincristine, doxorubicin hydrochloride, dexamethasone) chemotherapy and was doing well with plans for a fourth course of chemotherapy. There is no standardized treatment course for cutaneous PBL, though excision with adjunctive chemotherapy treatment commonly has been reported in the literature.¹

Plasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma associated with EBV infection that compromises approximately 2% to 3% of all HIV-related lymphomas.^1,2 It frequently is associated with immunosuppression in patients with HIV or in transplant recipients on immunosuppression; however, it has been reported in immunocompetent individuals such as elderly patients.² Plasmablastic lymphoma most commonly presents on the buccal mucosa but also can affect the gastrointestinal tract and occasionally has cutaneous manifestations.^1,2 Cutaneous manifestations of PBL range from erythematous infiltrated plaques to ulcerated nodules presenting in an array of colors from flesh colored to violaceous.² Primary cutaneous lesions can be seen on the legs, as in our patient.

Histopathologic examination reveals sheets of plasmablasts or large cells with eccentric nuclei and abundant basophilic cytoplasm.¹ Plasmablastic lymphoma frequently is positive for mature B-cell markers such as CD38, CD138, multiple myeloma 1, and B lymphocyte–induced maturation protein 1.^2,3 Uncommonly, PBL expresses paired box protein Pax-5 and CD20 markers.³ Although pathogenesis is poorly understood, it has been speculated that EBV infection is a common pathogenic factor. Epstein-Barr virus positivity has been noted in 60% of cases.²

Plasmablastic lymphoma and other malignant plasma cell processes such as plasmablastic myeloma (PBM) are morphologically similar. Proliferation of plasmablasts with rare plasmacytic cells is common in PBL, while plasmacytic cells are predominant in PBM. MYC rearrangement/ immunoglobulin heavy chain rearrangement t(8;14) was used to differentiate PBL from PBM in our patient; however, more cases of PBM with MYC/IGH rearrangement t(8;14) have been reported, making it an unreliable differentiating factor.⁴ A detailed clinical, pathologic, and genetic survey remains necessary for confirmatory diagnosis of PBL. Compared to other malignant plasma cell processes, PBL more commonly is seen in immunocompromised patients or those with HIV, such as our patient. Additionally, EBV testing is more likely to be positive in patients with PBL, further supporting this diagnosis in our patient.⁴

Presentations of bacillary angiomatosis, Kaposi sarcoma, and cutaneous lymphoma may be clinically similar; therefore, careful immunohistopathologic differentiation is necessary. Kaposi sarcoma is an angioproliferative disorder that develops from HHV-8 infection and commonly is associated with HIV. It presents as painless vascular lesions in a range of colors with typical progression from patch to plaque to nodules, frequently on the lower extremities. Histologically, admixtures of bland spindle cells, slitlike small vessel proliferation, and lymphocytic infiltration are typical. Neoplastic vessels lack basement membrane zones, resulting in microhemorrhages and hemosiderin deposition. Neoplastic vessels label with CD31 and CD34 endothelial markers in addition to HHV-8 antibodies, which is highly specific for Kaposi sarcoma and differentiates it from PBL.⁵

Bacillary angiomatosis is an infectious neovascular proliferation characterized by papular lesions that may resemble the lesions of PBL. Mixed cell infiltration in inflammatory cells with clumping of granular material is characteristic. Under Warthin-Starry staining, the granular material is abundant in gram-negative rods representing Bartonella species, which is the implicated infectious agent in bacillary angiomatosis.

Lymphomatoid papulosis (LyP) is the most common CD30+ lymphoproliferative disorder and also may present with exophytic nodules. The etiology of LyP remains unknown, but it is suspected that overexpression of CD30 plays a role. Lymphomatoid papulosis presents as red-violaceous papules and nodules in various stages of healing. Although variable histology among types of LyP exists, CD30+ T-cell lymphocytes remain the hallmark of LyP. Type A LyP, which accounts for 80% of LyP cases, reveals CD4+ and CD30+ cells scattered among neutrophils, eosinophils, and small lymphocytes.5 Lymphomatoid papulosis typically is self-healing, recurrent, and carries an excellent prognosis.

Plasmablastic lymphoma remains a rare and aggressive type of diffuse large B-cell lymphoma that can have primary cutaneous manifestations. It is prudent to consider PBL in the differential diagnosis of nodular lower extremity lesions, especially in immunosuppressed patients.

The Diagnosis: Plasmablastic Lymphoma

A punch biopsy of one of the leg nodules with hematoxylin and eosin staining revealed sheets of medium to large cells with plasmacytic differentiation (Figure, A and B). Immunohistochemistry showed CD79, epithelial membrane antigen, multiple myeloma 1, and CD138 positivity, as well as CD-19 negativity and positive staining on Epstein-Barr virus (EBV) in situ hybridization (Figure, C). Ki-67 stained greater than 90% of the neoplastic cells. Neoplastic cells were found to be λ restricted on κ and λ immunohistochemistry. Human herpesvirus 8 (HHV-8), CD3, and CD20 stains were negative. Subsequent fluorescent in situ hybridization was positive for MYC/immunoglobulin heavy chain (MYC/IGH) rearrangement t(8;14), confirming a diagnosis of plasmablastic lymphoma (PBL).

A bone marrow biopsy revealed normocellular bone marrow with trilineage hematopoiesis and no morphologic, immunophenotypic, or fluorescent in situ hybridization evidence of plasmablastic lymphoma or other pathology in the bone marrow. Our patient was started on hyper-CVAD (cyclophosphamide, vincristine, doxorubicin hydrochloride, dexamethasone) chemotherapy and was doing well with plans for a fourth course of chemotherapy. There is no standardized treatment course for cutaneous PBL, though excision with adjunctive chemotherapy treatment commonly has been reported in the literature.¹

Plasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma associated with EBV infection that compromises approximately 2% to 3% of all HIV-related lymphomas.^1,2 It frequently is associated with immunosuppression in patients with HIV or in transplant recipients on immunosuppression; however, it has been reported in immunocompetent individuals such as elderly patients.² Plasmablastic lymphoma most commonly presents on the buccal mucosa but also can affect the gastrointestinal tract and occasionally has cutaneous manifestations.^1,2 Cutaneous manifestations of PBL range from erythematous infiltrated plaques to ulcerated nodules presenting in an array of colors from flesh colored to violaceous.² Primary cutaneous lesions can be seen on the legs, as in our patient.

Histopathologic examination reveals sheets of plasmablasts or large cells with eccentric nuclei and abundant basophilic cytoplasm.¹ Plasmablastic lymphoma frequently is positive for mature B-cell markers such as CD38, CD138, multiple myeloma 1, and B lymphocyte–induced maturation protein 1.^2,3 Uncommonly, PBL expresses paired box protein Pax-5 and CD20 markers.³ Although pathogenesis is poorly understood, it has been speculated that EBV infection is a common pathogenic factor. Epstein-Barr virus positivity has been noted in 60% of cases.²

Plasmablastic lymphoma and other malignant plasma cell processes such as plasmablastic myeloma (PBM) are morphologically similar. Proliferation of plasmablasts with rare plasmacytic cells is common in PBL, while plasmacytic cells are predominant in PBM. MYC rearrangement/ immunoglobulin heavy chain rearrangement t(8;14) was used to differentiate PBL from PBM in our patient; however, more cases of PBM with MYC/IGH rearrangement t(8;14) have been reported, making it an unreliable differentiating factor.⁴ A detailed clinical, pathologic, and genetic survey remains necessary for confirmatory diagnosis of PBL. Compared to other malignant plasma cell processes, PBL more commonly is seen in immunocompromised patients or those with HIV, such as our patient. Additionally, EBV testing is more likely to be positive in patients with PBL, further supporting this diagnosis in our patient.⁴

Presentations of bacillary angiomatosis, Kaposi sarcoma, and cutaneous lymphoma may be clinically similar; therefore, careful immunohistopathologic differentiation is necessary. Kaposi sarcoma is an angioproliferative disorder that develops from HHV-8 infection and commonly is associated with HIV. It presents as painless vascular lesions in a range of colors with typical progression from patch to plaque to nodules, frequently on the lower extremities. Histologically, admixtures of bland spindle cells, slitlike small vessel proliferation, and lymphocytic infiltration are typical. Neoplastic vessels lack basement membrane zones, resulting in microhemorrhages and hemosiderin deposition. Neoplastic vessels label with CD31 and CD34 endothelial markers in addition to HHV-8 antibodies, which is highly specific for Kaposi sarcoma and differentiates it from PBL.⁵

Bacillary angiomatosis is an infectious neovascular proliferation characterized by papular lesions that may resemble the lesions of PBL. Mixed cell infiltration in inflammatory cells with clumping of granular material is characteristic. Under Warthin-Starry staining, the granular material is abundant in gram-negative rods representing Bartonella species, which is the implicated infectious agent in bacillary angiomatosis.

Lymphomatoid papulosis (LyP) is the most common CD30+ lymphoproliferative disorder and also may present with exophytic nodules. The etiology of LyP remains unknown, but it is suspected that overexpression of CD30 plays a role. Lymphomatoid papulosis presents as red-violaceous papules and nodules in various stages of healing. Although variable histology among types of LyP exists, CD30+ T-cell lymphocytes remain the hallmark of LyP. Type A LyP, which accounts for 80% of LyP cases, reveals CD4+ and CD30+ cells scattered among neutrophils, eosinophils, and small lymphocytes.5 Lymphomatoid papulosis typically is self-healing, recurrent, and carries an excellent prognosis.

Plasmablastic lymphoma remains a rare and aggressive type of diffuse large B-cell lymphoma that can have primary cutaneous manifestations. It is prudent to consider PBL in the differential diagnosis of nodular lower extremity lesions, especially in immunosuppressed patients.

The Diagnosis: Plasmablastic Lymphoma

A punch biopsy of one of the leg nodules with hematoxylin and eosin staining revealed sheets of medium to large cells with plasmacytic differentiation (Figure, A and B). Immunohistochemistry showed CD79, epithelial membrane antigen, multiple myeloma 1, and CD138 positivity, as well as CD-19 negativity and positive staining on Epstein-Barr virus (EBV) in situ hybridization (Figure, C). Ki-67 stained greater than 90% of the neoplastic cells. Neoplastic cells were found to be λ restricted on κ and λ immunohistochemistry. Human herpesvirus 8 (HHV-8), CD3, and CD20 stains were negative. Subsequent fluorescent in situ hybridization was positive for MYC/immunoglobulin heavy chain (MYC/IGH) rearrangement t(8;14), confirming a diagnosis of plasmablastic lymphoma (PBL).

A bone marrow biopsy revealed normocellular bone marrow with trilineage hematopoiesis and no morphologic, immunophenotypic, or fluorescent in situ hybridization evidence of plasmablastic lymphoma or other pathology in the bone marrow. Our patient was started on hyper-CVAD (cyclophosphamide, vincristine, doxorubicin hydrochloride, dexamethasone) chemotherapy and was doing well with plans for a fourth course of chemotherapy. There is no standardized treatment course for cutaneous PBL, though excision with adjunctive chemotherapy treatment commonly has been reported in the literature.¹

Plasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma associated with EBV infection that compromises approximately 2% to 3% of all HIV-related lymphomas.^1,2 It frequently is associated with immunosuppression in patients with HIV or in transplant recipients on immunosuppression; however, it has been reported in immunocompetent individuals such as elderly patients.² Plasmablastic lymphoma most commonly presents on the buccal mucosa but also can affect the gastrointestinal tract and occasionally has cutaneous manifestations.^1,2 Cutaneous manifestations of PBL range from erythematous infiltrated plaques to ulcerated nodules presenting in an array of colors from flesh colored to violaceous.² Primary cutaneous lesions can be seen on the legs, as in our patient.

Histopathologic examination reveals sheets of plasmablasts or large cells with eccentric nuclei and abundant basophilic cytoplasm.¹ Plasmablastic lymphoma frequently is positive for mature B-cell markers such as CD38, CD138, multiple myeloma 1, and B lymphocyte–induced maturation protein 1.^2,3 Uncommonly, PBL expresses paired box protein Pax-5 and CD20 markers.³ Although pathogenesis is poorly understood, it has been speculated that EBV infection is a common pathogenic factor. Epstein-Barr virus positivity has been noted in 60% of cases.²

Plasmablastic lymphoma and other malignant plasma cell processes such as plasmablastic myeloma (PBM) are morphologically similar. Proliferation of plasmablasts with rare plasmacytic cells is common in PBL, while plasmacytic cells are predominant in PBM. MYC rearrangement/ immunoglobulin heavy chain rearrangement t(8;14) was used to differentiate PBL from PBM in our patient; however, more cases of PBM with MYC/IGH rearrangement t(8;14) have been reported, making it an unreliable differentiating factor.⁴ A detailed clinical, pathologic, and genetic survey remains necessary for confirmatory diagnosis of PBL. Compared to other malignant plasma cell processes, PBL more commonly is seen in immunocompromised patients or those with HIV, such as our patient. Additionally, EBV testing is more likely to be positive in patients with PBL, further supporting this diagnosis in our patient.⁴

Presentations of bacillary angiomatosis, Kaposi sarcoma, and cutaneous lymphoma may be clinically similar; therefore, careful immunohistopathologic differentiation is necessary. Kaposi sarcoma is an angioproliferative disorder that develops from HHV-8 infection and commonly is associated with HIV. It presents as painless vascular lesions in a range of colors with typical progression from patch to plaque to nodules, frequently on the lower extremities. Histologically, admixtures of bland spindle cells, slitlike small vessel proliferation, and lymphocytic infiltration are typical. Neoplastic vessels lack basement membrane zones, resulting in microhemorrhages and hemosiderin deposition. Neoplastic vessels label with CD31 and CD34 endothelial markers in addition to HHV-8 antibodies, which is highly specific for Kaposi sarcoma and differentiates it from PBL.⁵

Bacillary angiomatosis is an infectious neovascular proliferation characterized by papular lesions that may resemble the lesions of PBL. Mixed cell infiltration in inflammatory cells with clumping of granular material is characteristic. Under Warthin-Starry staining, the granular material is abundant in gram-negative rods representing Bartonella species, which is the implicated infectious agent in bacillary angiomatosis.

Lymphomatoid papulosis (LyP) is the most common CD30+ lymphoproliferative disorder and also may present with exophytic nodules. The etiology of LyP remains unknown, but it is suspected that overexpression of CD30 plays a role. Lymphomatoid papulosis presents as red-violaceous papules and nodules in various stages of healing. Although variable histology among types of LyP exists, CD30+ T-cell lymphocytes remain the hallmark of LyP. Type A LyP, which accounts for 80% of LyP cases, reveals CD4+ and CD30+ cells scattered among neutrophils, eosinophils, and small lymphocytes.5 Lymphomatoid papulosis typically is self-healing, recurrent, and carries an excellent prognosis.

Plasmablastic lymphoma remains a rare and aggressive type of diffuse large B-cell lymphoma that can have primary cutaneous manifestations. It is prudent to consider PBL in the differential diagnosis of nodular lower extremity lesions, especially in immunosuppressed patients.

HONOLULU – Combining cryotherapy, salicylic acid, and fluorouracil (5-FU) can improve the efficacy of treating common warts, but topical or intralesional cidofovir may be required for recalcitrant lesions or those located in areas that are challenging to treat, according to John S. Barbieri, MD, MBA.

“There are 5 million office visits per year in the United States for warts and molluscum, and they’re most common in pediatrics,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “In fact, some studies have suggested that one in three children in primary school suffers from warts.”

Doug Brunk/MDedge News

According to a 2012 Cochrane review of topical therapies for warts, first-line treatments such as salicylic acid, cryotherapy, 5-FU, or Candida antigen injection often have modest efficacy when used alone. For example, the authors found that salicylic acid and cryotherapy cleared warts in about 60%-70% of cases, respectively, but clearance rates were improved by combining the two therapies.

In an earlier literature review and meta-analysis, investigators evaluated the effect of 5-FU plus salicylic acid or salicylic acid alone. The therapeutic effect for common warts across all studies was a 63.4% response rate (complete healing) for 5-FU/SA vversus 23.1% for the 5-FU–free controls, respectively. For plantar warts, the response rate was 63% versus 11%, respectively.

“But what about the person with multiple warts or those in challenging locations where you might worry about destructive treatments hurting the nail fold or causing nail dystrophy?” Dr. Barbieri asked. “Maybe they’ve used salicylic acid or intralesional Candida and they’re still not getting better. What can we do for these patients?”

Emerging research suggests that topical cidofovir can be a valuable option for recalcitrant warts or those in sensitive locations. In a case report of a 10-year-old boy with more than 50 severe verrucous papules on his hands and face that were recalcitrant to multiple conventional therapies, topical 1% cidofovir applied daily for 8 weeks was effective, with no adverse side effects. A young female patient who presented to Dr. Barbieri with multiple warts around the nail matrix of several fingers experienced complete clearance after treatment with topical cidofovir, he said. Other researchers found this approach to be effective for plantar warts as well, in a report of two brothers with severe combined immunodeficiency after hematopoietic stem cell transplantation with persistent warts that did not respond to traditional topical treatments.

David Carillet/Dreamstime

“Topical cidofovir is typically a painless treatment, which is nice, especially for our pediatric patients who might be afraid of other therapies like or cryotherapy or intralesional injections,” One limitation is that it is “a bit expensive,” Dr. Barbieri said. “To have topical cidofovir compounded is typically $100-$300, depending on the quantity and strength that you ask for.”

Intralesional cidofovir is another treatment option. In a retrospective study of 58 patients, Dr. Barbieri and colleagues evaluated the outcome of intralesional cidofovir treatment of warts in immunocompromised and nonimmunocompromised patients. Rates of improvement ranged from 98.3% to 100%, while resolution rates ranged from 75.9% to 97.6%.

“Most of the patients had warts for more than 5 years and almost half of them had recalcitrant warts,” Dr. Barbieri said. “These were mostly adult patients, but I think this is a treatment that can work in younger populations as well. About 10%-15% had HIV or cancer or diabetes or were transplant recipients, but despite these challenges and despite these recalcitrant warts, about 100% had improvement.”

He pointed out that cidofovir is available as a 75 mg/mL vial that comes with a 5 mL single-use vial. He dilutes this with normal saline to create a 15 mg/mL solution.

“If you want to be efficient you can try to schedule multiple patients together on the same day as a single vial is sufficient to treat about 25 patients,” assuming about 1 mL is injected per patient, he said. “The challenge with intralesional cidofovir is that it’s painful beyond just the needle part of the injection. Sometimes a nerve block can be helpful. But this can be an effective treatment for patients with recalcitrant warts or those with comorbidities.”

Other intralesional therapies to try for recalcitrant warts, he said, include bleomycin (1 U/mL solution, 1-2 mL per treatment, spaced every 2-4 weeks), and 5-FU (a 4:1 mixture of 5-FU [50 mg/mL] and 2% lidocaine).

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Medscape and this news organization are owned by the same parent company.

HONOLULU – Combining cryotherapy, salicylic acid, and fluorouracil (5-FU) can improve the efficacy of treating common warts, but topical or intralesional cidofovir may be required for recalcitrant lesions or those located in areas that are challenging to treat, according to John S. Barbieri, MD, MBA.

“There are 5 million office visits per year in the United States for warts and molluscum, and they’re most common in pediatrics,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “In fact, some studies have suggested that one in three children in primary school suffers from warts.”

Doug Brunk/MDedge News

According to a 2012 Cochrane review of topical therapies for warts, first-line treatments such as salicylic acid, cryotherapy, 5-FU, or Candida antigen injection often have modest efficacy when used alone. For example, the authors found that salicylic acid and cryotherapy cleared warts in about 60%-70% of cases, respectively, but clearance rates were improved by combining the two therapies.

In an earlier literature review and meta-analysis, investigators evaluated the effect of 5-FU plus salicylic acid or salicylic acid alone. The therapeutic effect for common warts across all studies was a 63.4% response rate (complete healing) for 5-FU/SA vversus 23.1% for the 5-FU–free controls, respectively. For plantar warts, the response rate was 63% versus 11%, respectively.

“But what about the person with multiple warts or those in challenging locations where you might worry about destructive treatments hurting the nail fold or causing nail dystrophy?” Dr. Barbieri asked. “Maybe they’ve used salicylic acid or intralesional Candida and they’re still not getting better. What can we do for these patients?”

Emerging research suggests that topical cidofovir can be a valuable option for recalcitrant warts or those in sensitive locations. In a case report of a 10-year-old boy with more than 50 severe verrucous papules on his hands and face that were recalcitrant to multiple conventional therapies, topical 1% cidofovir applied daily for 8 weeks was effective, with no adverse side effects. A young female patient who presented to Dr. Barbieri with multiple warts around the nail matrix of several fingers experienced complete clearance after treatment with topical cidofovir, he said. Other researchers found this approach to be effective for plantar warts as well, in a report of two brothers with severe combined immunodeficiency after hematopoietic stem cell transplantation with persistent warts that did not respond to traditional topical treatments.

David Carillet/Dreamstime

“Topical cidofovir is typically a painless treatment, which is nice, especially for our pediatric patients who might be afraid of other therapies like or cryotherapy or intralesional injections,” One limitation is that it is “a bit expensive,” Dr. Barbieri said. “To have topical cidofovir compounded is typically $100-$300, depending on the quantity and strength that you ask for.”

Intralesional cidofovir is another treatment option. In a retrospective study of 58 patients, Dr. Barbieri and colleagues evaluated the outcome of intralesional cidofovir treatment of warts in immunocompromised and nonimmunocompromised patients. Rates of improvement ranged from 98.3% to 100%, while resolution rates ranged from 75.9% to 97.6%.

“Most of the patients had warts for more than 5 years and almost half of them had recalcitrant warts,” Dr. Barbieri said. “These were mostly adult patients, but I think this is a treatment that can work in younger populations as well. About 10%-15% had HIV or cancer or diabetes or were transplant recipients, but despite these challenges and despite these recalcitrant warts, about 100% had improvement.”

He pointed out that cidofovir is available as a 75 mg/mL vial that comes with a 5 mL single-use vial. He dilutes this with normal saline to create a 15 mg/mL solution.

“If you want to be efficient you can try to schedule multiple patients together on the same day as a single vial is sufficient to treat about 25 patients,” assuming about 1 mL is injected per patient, he said. “The challenge with intralesional cidofovir is that it’s painful beyond just the needle part of the injection. Sometimes a nerve block can be helpful. But this can be an effective treatment for patients with recalcitrant warts or those with comorbidities.”

Other intralesional therapies to try for recalcitrant warts, he said, include bleomycin (1 U/mL solution, 1-2 mL per treatment, spaced every 2-4 weeks), and 5-FU (a 4:1 mixture of 5-FU [50 mg/mL] and 2% lidocaine).

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Medscape and this news organization are owned by the same parent company.

HONOLULU – Combining cryotherapy, salicylic acid, and fluorouracil (5-FU) can improve the efficacy of treating common warts, but topical or intralesional cidofovir may be required for recalcitrant lesions or those located in areas that are challenging to treat, according to John S. Barbieri, MD, MBA.

“There are 5 million office visits per year in the United States for warts and molluscum, and they’re most common in pediatrics,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “In fact, some studies have suggested that one in three children in primary school suffers from warts.”

Doug Brunk/MDedge News

According to a 2012 Cochrane review of topical therapies for warts, first-line treatments such as salicylic acid, cryotherapy, 5-FU, or Candida antigen injection often have modest efficacy when used alone. For example, the authors found that salicylic acid and cryotherapy cleared warts in about 60%-70% of cases, respectively, but clearance rates were improved by combining the two therapies.

In an earlier literature review and meta-analysis, investigators evaluated the effect of 5-FU plus salicylic acid or salicylic acid alone. The therapeutic effect for common warts across all studies was a 63.4% response rate (complete healing) for 5-FU/SA vversus 23.1% for the 5-FU–free controls, respectively. For plantar warts, the response rate was 63% versus 11%, respectively.

“But what about the person with multiple warts or those in challenging locations where you might worry about destructive treatments hurting the nail fold or causing nail dystrophy?” Dr. Barbieri asked. “Maybe they’ve used salicylic acid or intralesional Candida and they’re still not getting better. What can we do for these patients?”

Emerging research suggests that topical cidofovir can be a valuable option for recalcitrant warts or those in sensitive locations. In a case report of a 10-year-old boy with more than 50 severe verrucous papules on his hands and face that were recalcitrant to multiple conventional therapies, topical 1% cidofovir applied daily for 8 weeks was effective, with no adverse side effects. A young female patient who presented to Dr. Barbieri with multiple warts around the nail matrix of several fingers experienced complete clearance after treatment with topical cidofovir, he said. Other researchers found this approach to be effective for plantar warts as well, in a report of two brothers with severe combined immunodeficiency after hematopoietic stem cell transplantation with persistent warts that did not respond to traditional topical treatments.

David Carillet/Dreamstime

“Topical cidofovir is typically a painless treatment, which is nice, especially for our pediatric patients who might be afraid of other therapies like or cryotherapy or intralesional injections,” One limitation is that it is “a bit expensive,” Dr. Barbieri said. “To have topical cidofovir compounded is typically $100-$300, depending on the quantity and strength that you ask for.”

Intralesional cidofovir is another treatment option. In a retrospective study of 58 patients, Dr. Barbieri and colleagues evaluated the outcome of intralesional cidofovir treatment of warts in immunocompromised and nonimmunocompromised patients. Rates of improvement ranged from 98.3% to 100%, while resolution rates ranged from 75.9% to 97.6%.

“Most of the patients had warts for more than 5 years and almost half of them had recalcitrant warts,” Dr. Barbieri said. “These were mostly adult patients, but I think this is a treatment that can work in younger populations as well. About 10%-15% had HIV or cancer or diabetes or were transplant recipients, but despite these challenges and despite these recalcitrant warts, about 100% had improvement.”

He pointed out that cidofovir is available as a 75 mg/mL vial that comes with a 5 mL single-use vial. He dilutes this with normal saline to create a 15 mg/mL solution.

“If you want to be efficient you can try to schedule multiple patients together on the same day as a single vial is sufficient to treat about 25 patients,” assuming about 1 mL is injected per patient, he said. “The challenge with intralesional cidofovir is that it’s painful beyond just the needle part of the injection. Sometimes a nerve block can be helpful. But this can be an effective treatment for patients with recalcitrant warts or those with comorbidities.”

Other intralesional therapies to try for recalcitrant warts, he said, include bleomycin (1 U/mL solution, 1-2 mL per treatment, spaced every 2-4 weeks), and 5-FU (a 4:1 mixture of 5-FU [50 mg/mL] and 2% lidocaine).

Dr. Barbieri disclosed that he receives consulting fees from Dexcel for work unrelated to his presentation. Medscape and this news organization are owned by the same parent company.

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

A version of this article first appeared on Medscape.com.

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

A version of this article first appeared on Medscape.com.

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

A version of this article first appeared on Medscape.com.

Do not purchase or use Delsam Pharma’s Artificial Eye Ointment, the Food and Drug Administration warns.

The announcement released Wednesday adds to a previous warning issued earlier this month for EzriCare Artificial Tears or Delsam Pharma’s Artificial Tears because of potential bacterial contamination. All three products are manufactured by the same company, Global Pharma Healthcare, based in Tamilnadu, India.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA has faulted the company for multiple violations, including “lack of appropriate microbial testing” and “lack of proper controls concerning tamper-evident packaging,” and has banned imports to the United States.

The updated warning from the FDA did not give additional information about the over-the-counter eye ointment beyond potential bacterial contamination. 

On Feb. 1, the CDC issued an alert about an outbreak of a drug-resistant strain of bacteria, Pseudomonas aeruginosa, linked to artificial tear products. To date, 58 patients across 13 states have been identified, and the most commonly reported artificial tear brand was EzriCare Artificial Tears. Five patients had permanent vision loss, and one patient died.

A version of this article first appeared on Medscape.com.

Do not purchase or use Delsam Pharma’s Artificial Eye Ointment, the Food and Drug Administration warns.

The announcement released Wednesday adds to a previous warning issued earlier this month for EzriCare Artificial Tears or Delsam Pharma’s Artificial Tears because of potential bacterial contamination. All three products are manufactured by the same company, Global Pharma Healthcare, based in Tamilnadu, India.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA has faulted the company for multiple violations, including “lack of appropriate microbial testing” and “lack of proper controls concerning tamper-evident packaging,” and has banned imports to the United States.

The updated warning from the FDA did not give additional information about the over-the-counter eye ointment beyond potential bacterial contamination. 

On Feb. 1, the CDC issued an alert about an outbreak of a drug-resistant strain of bacteria, Pseudomonas aeruginosa, linked to artificial tear products. To date, 58 patients across 13 states have been identified, and the most commonly reported artificial tear brand was EzriCare Artificial Tears. Five patients had permanent vision loss, and one patient died.

A version of this article first appeared on Medscape.com.

Do not purchase or use Delsam Pharma’s Artificial Eye Ointment, the Food and Drug Administration warns.

The announcement released Wednesday adds to a previous warning issued earlier this month for EzriCare Artificial Tears or Delsam Pharma’s Artificial Tears because of potential bacterial contamination. All three products are manufactured by the same company, Global Pharma Healthcare, based in Tamilnadu, India.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA has faulted the company for multiple violations, including “lack of appropriate microbial testing” and “lack of proper controls concerning tamper-evident packaging,” and has banned imports to the United States.

The updated warning from the FDA did not give additional information about the over-the-counter eye ointment beyond potential bacterial contamination. 

On Feb. 1, the CDC issued an alert about an outbreak of a drug-resistant strain of bacteria, Pseudomonas aeruginosa, linked to artificial tear products. To date, 58 patients across 13 states have been identified, and the most commonly reported artificial tear brand was EzriCare Artificial Tears. Five patients had permanent vision loss, and one patient died.

A version of this article first appeared on Medscape.com.

The latest study to show high efficacy of doxycycline post-exposure prophylaxis (Doxy PEP) in preventing sexually transmitted infections among men who have sex with men (MSM) adds a new twist, showing – for the first time – reductions in gonorrhea among those receiving the meningococcal B vaccine.

“Among men who have sex with men on HIV PrEP, doxycycline PEP significantly reduced the incidence of chlamydia and syphilis and also had a significant impact on the incidence of gonorrhea,” said first author Jean-Michel Molina, MD, PhD, in presenting the findings at the Conference on Retroviruses and Opportunistic Infections.

In addition, “two doses of the meningococcal B vaccine reduced the incidence of a first episode of gonorrhea by roughly 50% among men who have sex with men,” said Dr. Molina, a professor of infectious diseases at the University of Paris, and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals, Paris.

Whereas the advent of PrEP has been associated with significant reductions in HIV transmission, rates of STIs have conversely been on the rise among MSM, specifically among those receiving PrEP.

Post-exposure prophylaxis with Doxy PEP has been shown to reduce the incidence of chlamydia and syphilis by approximately 70%; however, effects on prevention of gonorrhea have been less clear.

Meningococcal B vaccination has, meanwhile, shown intriguing reductions of gonorrhea incidence of as much as 26%-46% in some observational studies.

Therefore, Dr. Molina and colleagues decided to further investigate Doxy PEP as well as the meningococcal B vaccine in prevention of STIs.

For the ANRS 174 DOXYVAC trial, they enrolled 546 MSM in the open-label, multicenter study between January 2021 and July 2022.

The men were randomly assigned to one of 4 groups: doxycycline postexposure prophylaxis (Doxy PEP: 200 mg; n = 332), no Doxy PEP (n = 170), two shots of meningococcal B vaccine (4CMenB vaccine; n = 257), or no 4CMenB vaccine (n = 245).

All participants were assigned to their groups within 72 hours of condomless sex.

The men, who had a median age of 39, had a median time of PrEP use of 42 months, a history of an STI in the past year, and their median number of sexual partners in the past 3 months was 10.

Their characteristics were well-balanced across the treatment groups. After discontinuations of 54 patients across the groups, the final analysis included 502 participants.

With a median follow-up of 9 months, the intent-to-treat analysis showed 13 subjects had a first episode of chlamydia or syphilis in the Doxy PEP group, versus 49 subjects infected in the no Doxy PEP arm, for an incidence of 5.6 versus 35.4 per 100 person-years, respectively (adjusted hazard ratio, 0.16; P < .0001).

Infection specifically with chlamydia occurred among 21 men with no Doxy PEP versus 5 receiving Dox PEP (19.3 vs. 2.1 per 100 person-years, respectively; HR, 0.11; P < .0001).

And infection with syphilis occurred in 18 men receiving no Doxy PEP versus 8 receiving the treatment (16.3 vs. 3.4 per 100 person-years, respectively; HR, 0.21; P < .001).

The corresponding rates for gonorrhea infection were an incidence 41.3 versus 20.5 per 100 person-years, in the no Doxy PEP versus Doxy PEP arms, respectively (adjusted HR, 0.49; P = .001), and 29.4 versus 16.8 per 100 person-years for Mycoplasma genitalium infection (aHR, 0.55; P = .015).

Throughout the study, about 80% of patients in the Doxy PEP group reported using the prophylaxis treatment after their most recent sexual intercourse, with subjects reporting taking a median of seven pills per month.

In the vaccine/no vaccine comparisons, 32 subjects in the no meningococcal vaccine group were infected with a first gonorrhea infection, compared with 17 in the vaccine group, representing an incidence of 19.7 versus 9.8 per 100 person-years, respectively (adjusted HR, 0.49; P = .016), which Dr. Molina called “highly significant.”

An analysis of the cumulative incidence of gonorrhea infection with the meningococcal vaccine showed rates in the no vaccine versus vaccine groups of 30.4 versus 20.1 per 100 person-years, respectively; however, statistical significance was not reached (aHR, 0.66; P = .052).

Importantly, there were no significant interactions in the results between those receiving Doxy PEP or the 4CMenB vaccine group, and there were no significant differences in drug-related serious adverse events between the groups.

Dr. Molina noted that the meningococcal B vaccine is known to contain key antigens that are shared between meningitis and gonorrhea, which could explain the benefits.

Although chlamydia and syphilis thus far appear to remain susceptible to Doxy PEP, resistances with gonorrhea remain a concern, hence the ability of the vaccine to provide some protection could be an added bonus.

“We know that [gonorrhea] is able to very quickly develop resistances to any antibiotics, so that was why we wanted to look beyond the antibiotic prophylaxis,” said Dr. Molina.

Among questions to explore looking ahead is the potential longevity of protection with the vaccine.

“We don’t know at this point how long the protection with the vaccine could last, or if [people] may need booster injections, for instance, but the literature suggests benefits for at least a year,” Dr. Molina said. “We are still monitoring the patients in the study to see what happens.”

He added that combination of the interventions may be of benefit.

“In the future, we think we may need to combine these approaches if we want to meet the WHO/UNAIDS targets to reduce the incidence of HIV and STIs by 90% by 2030.”

Commenting on the study, CROI vice-chair Landon Myer, MD, PhD, noted that “gonorrhea develops resistance quickly and can be hard to treat or prophylaxis, so the vaccine finding, which was hinted at by previous observational data, is really important.”

He agrees that “the duration of protective efficacy – a big thing in vaccines – is unknown.”

“Still, this is really significant,” Dr. Myer stressed. “An efficacious vaccine against a stubborn sexually transmitted infection.”

A version of this article first appeared on Medscape.com.

The latest study to show high efficacy of doxycycline post-exposure prophylaxis (Doxy PEP) in preventing sexually transmitted infections among men who have sex with men (MSM) adds a new twist, showing – for the first time – reductions in gonorrhea among those receiving the meningococcal B vaccine.

“Among men who have sex with men on HIV PrEP, doxycycline PEP significantly reduced the incidence of chlamydia and syphilis and also had a significant impact on the incidence of gonorrhea,” said first author Jean-Michel Molina, MD, PhD, in presenting the findings at the Conference on Retroviruses and Opportunistic Infections.

In addition, “two doses of the meningococcal B vaccine reduced the incidence of a first episode of gonorrhea by roughly 50% among men who have sex with men,” said Dr. Molina, a professor of infectious diseases at the University of Paris, and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals, Paris.

Whereas the advent of PrEP has been associated with significant reductions in HIV transmission, rates of STIs have conversely been on the rise among MSM, specifically among those receiving PrEP.

Post-exposure prophylaxis with Doxy PEP has been shown to reduce the incidence of chlamydia and syphilis by approximately 70%; however, effects on prevention of gonorrhea have been less clear.

Meningococcal B vaccination has, meanwhile, shown intriguing reductions of gonorrhea incidence of as much as 26%-46% in some observational studies.

Therefore, Dr. Molina and colleagues decided to further investigate Doxy PEP as well as the meningococcal B vaccine in prevention of STIs.

For the ANRS 174 DOXYVAC trial, they enrolled 546 MSM in the open-label, multicenter study between January 2021 and July 2022.

The men were randomly assigned to one of 4 groups: doxycycline postexposure prophylaxis (Doxy PEP: 200 mg; n = 332), no Doxy PEP (n = 170), two shots of meningococcal B vaccine (4CMenB vaccine; n = 257), or no 4CMenB vaccine (n = 245).

All participants were assigned to their groups within 72 hours of condomless sex.

The men, who had a median age of 39, had a median time of PrEP use of 42 months, a history of an STI in the past year, and their median number of sexual partners in the past 3 months was 10.

Their characteristics were well-balanced across the treatment groups. After discontinuations of 54 patients across the groups, the final analysis included 502 participants.

With a median follow-up of 9 months, the intent-to-treat analysis showed 13 subjects had a first episode of chlamydia or syphilis in the Doxy PEP group, versus 49 subjects infected in the no Doxy PEP arm, for an incidence of 5.6 versus 35.4 per 100 person-years, respectively (adjusted hazard ratio, 0.16; P < .0001).

Infection specifically with chlamydia occurred among 21 men with no Doxy PEP versus 5 receiving Dox PEP (19.3 vs. 2.1 per 100 person-years, respectively; HR, 0.11; P < .0001).

And infection with syphilis occurred in 18 men receiving no Doxy PEP versus 8 receiving the treatment (16.3 vs. 3.4 per 100 person-years, respectively; HR, 0.21; P < .001).

The corresponding rates for gonorrhea infection were an incidence 41.3 versus 20.5 per 100 person-years, in the no Doxy PEP versus Doxy PEP arms, respectively (adjusted HR, 0.49; P = .001), and 29.4 versus 16.8 per 100 person-years for Mycoplasma genitalium infection (aHR, 0.55; P = .015).

Throughout the study, about 80% of patients in the Doxy PEP group reported using the prophylaxis treatment after their most recent sexual intercourse, with subjects reporting taking a median of seven pills per month.

In the vaccine/no vaccine comparisons, 32 subjects in the no meningococcal vaccine group were infected with a first gonorrhea infection, compared with 17 in the vaccine group, representing an incidence of 19.7 versus 9.8 per 100 person-years, respectively (adjusted HR, 0.49; P = .016), which Dr. Molina called “highly significant.”

An analysis of the cumulative incidence of gonorrhea infection with the meningococcal vaccine showed rates in the no vaccine versus vaccine groups of 30.4 versus 20.1 per 100 person-years, respectively; however, statistical significance was not reached (aHR, 0.66; P = .052).

Importantly, there were no significant interactions in the results between those receiving Doxy PEP or the 4CMenB vaccine group, and there were no significant differences in drug-related serious adverse events between the groups.

Dr. Molina noted that the meningococcal B vaccine is known to contain key antigens that are shared between meningitis and gonorrhea, which could explain the benefits.

Although chlamydia and syphilis thus far appear to remain susceptible to Doxy PEP, resistances with gonorrhea remain a concern, hence the ability of the vaccine to provide some protection could be an added bonus.

“We know that [gonorrhea] is able to very quickly develop resistances to any antibiotics, so that was why we wanted to look beyond the antibiotic prophylaxis,” said Dr. Molina.

Among questions to explore looking ahead is the potential longevity of protection with the vaccine.

“We don’t know at this point how long the protection with the vaccine could last, or if [people] may need booster injections, for instance, but the literature suggests benefits for at least a year,” Dr. Molina said. “We are still monitoring the patients in the study to see what happens.”

He added that combination of the interventions may be of benefit.

“In the future, we think we may need to combine these approaches if we want to meet the WHO/UNAIDS targets to reduce the incidence of HIV and STIs by 90% by 2030.”

Commenting on the study, CROI vice-chair Landon Myer, MD, PhD, noted that “gonorrhea develops resistance quickly and can be hard to treat or prophylaxis, so the vaccine finding, which was hinted at by previous observational data, is really important.”

He agrees that “the duration of protective efficacy – a big thing in vaccines – is unknown.”

“Still, this is really significant,” Dr. Myer stressed. “An efficacious vaccine against a stubborn sexually transmitted infection.”

A version of this article first appeared on Medscape.com.

The latest study to show high efficacy of doxycycline post-exposure prophylaxis (Doxy PEP) in preventing sexually transmitted infections among men who have sex with men (MSM) adds a new twist, showing – for the first time – reductions in gonorrhea among those receiving the meningococcal B vaccine.

“Among men who have sex with men on HIV PrEP, doxycycline PEP significantly reduced the incidence of chlamydia and syphilis and also had a significant impact on the incidence of gonorrhea,” said first author Jean-Michel Molina, MD, PhD, in presenting the findings at the Conference on Retroviruses and Opportunistic Infections.

In addition, “two doses of the meningococcal B vaccine reduced the incidence of a first episode of gonorrhea by roughly 50% among men who have sex with men,” said Dr. Molina, a professor of infectious diseases at the University of Paris, and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals, Paris.

Whereas the advent of PrEP has been associated with significant reductions in HIV transmission, rates of STIs have conversely been on the rise among MSM, specifically among those receiving PrEP.

Post-exposure prophylaxis with Doxy PEP has been shown to reduce the incidence of chlamydia and syphilis by approximately 70%; however, effects on prevention of gonorrhea have been less clear.

Meningococcal B vaccination has, meanwhile, shown intriguing reductions of gonorrhea incidence of as much as 26%-46% in some observational studies.

Therefore, Dr. Molina and colleagues decided to further investigate Doxy PEP as well as the meningococcal B vaccine in prevention of STIs.

For the ANRS 174 DOXYVAC trial, they enrolled 546 MSM in the open-label, multicenter study between January 2021 and July 2022.

The men were randomly assigned to one of 4 groups: doxycycline postexposure prophylaxis (Doxy PEP: 200 mg; n = 332), no Doxy PEP (n = 170), two shots of meningococcal B vaccine (4CMenB vaccine; n = 257), or no 4CMenB vaccine (n = 245).

All participants were assigned to their groups within 72 hours of condomless sex.

The men, who had a median age of 39, had a median time of PrEP use of 42 months, a history of an STI in the past year, and their median number of sexual partners in the past 3 months was 10.

Their characteristics were well-balanced across the treatment groups. After discontinuations of 54 patients across the groups, the final analysis included 502 participants.

With a median follow-up of 9 months, the intent-to-treat analysis showed 13 subjects had a first episode of chlamydia or syphilis in the Doxy PEP group, versus 49 subjects infected in the no Doxy PEP arm, for an incidence of 5.6 versus 35.4 per 100 person-years, respectively (adjusted hazard ratio, 0.16; P < .0001).

Infection specifically with chlamydia occurred among 21 men with no Doxy PEP versus 5 receiving Dox PEP (19.3 vs. 2.1 per 100 person-years, respectively; HR, 0.11; P < .0001).

And infection with syphilis occurred in 18 men receiving no Doxy PEP versus 8 receiving the treatment (16.3 vs. 3.4 per 100 person-years, respectively; HR, 0.21; P < .001).

The corresponding rates for gonorrhea infection were an incidence 41.3 versus 20.5 per 100 person-years, in the no Doxy PEP versus Doxy PEP arms, respectively (adjusted HR, 0.49; P = .001), and 29.4 versus 16.8 per 100 person-years for Mycoplasma genitalium infection (aHR, 0.55; P = .015).

Throughout the study, about 80% of patients in the Doxy PEP group reported using the prophylaxis treatment after their most recent sexual intercourse, with subjects reporting taking a median of seven pills per month.

In the vaccine/no vaccine comparisons, 32 subjects in the no meningococcal vaccine group were infected with a first gonorrhea infection, compared with 17 in the vaccine group, representing an incidence of 19.7 versus 9.8 per 100 person-years, respectively (adjusted HR, 0.49; P = .016), which Dr. Molina called “highly significant.”

An analysis of the cumulative incidence of gonorrhea infection with the meningococcal vaccine showed rates in the no vaccine versus vaccine groups of 30.4 versus 20.1 per 100 person-years, respectively; however, statistical significance was not reached (aHR, 0.66; P = .052).

Importantly, there were no significant interactions in the results between those receiving Doxy PEP or the 4CMenB vaccine group, and there were no significant differences in drug-related serious adverse events between the groups.

Dr. Molina noted that the meningococcal B vaccine is known to contain key antigens that are shared between meningitis and gonorrhea, which could explain the benefits.

Although chlamydia and syphilis thus far appear to remain susceptible to Doxy PEP, resistances with gonorrhea remain a concern, hence the ability of the vaccine to provide some protection could be an added bonus.

“We know that [gonorrhea] is able to very quickly develop resistances to any antibiotics, so that was why we wanted to look beyond the antibiotic prophylaxis,” said Dr. Molina.

Among questions to explore looking ahead is the potential longevity of protection with the vaccine.

“We don’t know at this point how long the protection with the vaccine could last, or if [people] may need booster injections, for instance, but the literature suggests benefits for at least a year,” Dr. Molina said. “We are still monitoring the patients in the study to see what happens.”

He added that combination of the interventions may be of benefit.

“In the future, we think we may need to combine these approaches if we want to meet the WHO/UNAIDS targets to reduce the incidence of HIV and STIs by 90% by 2030.”

Commenting on the study, CROI vice-chair Landon Myer, MD, PhD, noted that “gonorrhea develops resistance quickly and can be hard to treat or prophylaxis, so the vaccine finding, which was hinted at by previous observational data, is really important.”

He agrees that “the duration of protective efficacy – a big thing in vaccines – is unknown.”

“Still, this is really significant,” Dr. Myer stressed. “An efficacious vaccine against a stubborn sexually transmitted infection.”

A version of this article first appeared on Medscape.com.

To the Editor:

One of the more common tick-borne infections seen in travelers returning from sub-Saharan Africa is caused by Rickettsia africae, which is the etiologic agent of African tick-bite fever (ATBF), the most common tick-borne bacterial zoonosis.¹ There are 2 known tick vectors of disease: Amblyomma variegatum, found in sub-Saharan Africa and the West Indies, and Amblyomma hebraeum, found specifically in southern Africa.^2,3

Unlike other disease-carrying ticks that passively wait on vegetation to be picked up by a host, A hebraeum uniquely attract other nearby ticks to the host. Studies have shown that male ticks feeding on a nonhuman host (usually cattle) can emit an aggression-attachment pheromone that attracts other ticks to the host. The presence of the pheromone allows unfed ticks to actively discriminate between hosts on which these parasites have fed successfully (ie, suitable hosts) and those on which they have not.⁴

The aggressive hunting nature of A hebraeum explains the clinical presentation of multiple eschars and why large groups of exposed travelers—such as soldiers, leisure safari tourists, game hunters, and foreign-aid workers—are affected.²

Another southern African spotted fever group, Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF). Ticks carrying R conorii exhibit a much less aggressive hunting stylethan A hebraeum; consequently, infected patients present with a single eschar site.⁵

Rickettsia africae is estimated to have very high prevalence (95.2%) in Amblyomma ticks and a fairly high prevalence (approximately 4.0% to 8.6%) in travelers coming from rural southern Africa,^6,7 with an incubation period of 5 to 10 days after inoculation by an infected tick.⁸ Signs include fever, a generalized maculopapular or papulovesicular rash, and regional lymphadenopathy; symptoms include fatigue, headache, and myalgia.

The inoculation eschar—single or multiple—commonly presents on the legs and is accompanied by tender lymphadenopathy of draining nodes^1,8 More severe findings, such as myocarditis and subacute neuropathy, have been reported in elderly patients.⁹

A 77-year-old man presented with a pruritic maculopapular and papulovesicular rash distributed over the upper and lower extremities of 3 weeks’ duration. The patient reported having been on a 12-day mission trip to Limpopo, South Africa, where he was constructing and installing safe toilets to replace dangerous toilet pits. He believed he had been bitten by 2 ticks, after which he noted a dark purple and black patch on the left lower leg by the third day of the trip. He developed a sudden persistent pruritic rash, first on the lower extremities and then spreading to the upper extremities. The patient was seen by an American physician in South Africa who gave him a 7-day course of oral doxycycline monohydrate 100 mg twice daily. He then returned to the United States.

Sixteen days after being bitten by the ticks, the patient was examined in our dermatology office. Physical examination revealed an erythematous plaque with a central eschar over the medial aspect of the left leg (Figure 1) and multiple 3- to 6-mm, erythematous, dome-shaped papules scattered over the dorsal aspects of the feet and ankles (Figure 2). The examination was otherwise normal. Blood was drawn the same day for laboratory analysis; no abnormalities of platelets, red blood cells, or white blood cells were found. Results of a chemistry panel and liver enzyme tests were within reference range.

Skin biopsies were taken to elucidate the underlying pathology. Although an arthropod assault was suspected, there also was concern for deep vessel vasculitis because of the presence of considerable petechiae and purpura (Figure 3). Histologically, leukocytoclasia was seen in deep dermal blood vessels. A mild eosinophilic spongiosis with a mixed dermal infiltrate was identified—strengthening our suspicion of an arthropod assault. Bacterial cultures for aerobes and anaerobes using material taken from the right shin showed no growth.

Ten days after the initial biopsies, serum specimens were drawn and swabs of eschar were collected and sent to the Centers for Disease Control and Prevention for further testing. Serum was tested by immunofluorescence assay (IFA) for spotted fever group IgG to detect Rocky Mountain spotted fever and ATBF antibodies; both tests were negative. Swab material from eschar was tested again by IFA for spotted fever group IgG (Rocky Mountain spotted fever) and antibodies to ATBF and with bacterial culture isolation and nucleic acid amplification; the culture and amplification came back positive for R africae.

Because the specialized tests confirmed infection with R africae, the patient was given triamcinolone cream 0.1% to apply twice daily to the pruritic lesions for as long as 4 weeks; an additional 14-day course of oral doxycycline monohydrate (100 mg twice daily) was given. At follow-up, the lesions had fully resolved without evident scarring.

Various diagnostic techniques can detect R africae. Bacterial culture and the polymerase chain reaction are specific and therefore diagnostic. In addition, the diagnosis of rickettsiosis can be made with serology testing, in which disease-specific antibodies are detected by indirect IFA using disease-specific antigens.

Antigens from R rickettsii (the agent of Rocky Mountain spotted fever), R conorii (Mediterranean spotted fever), and R africae (ATBF) are commercially available for making the diagnosis of rickettsiosis. However, antigens from R conorii exhibit cross-reactivity with R africae, which can confound the diagnosis.^1,10 Serologic IFA tests have been shown to be less sensitive, especially when performed after antibacterial treatment has started.

In a study, 17 of 65 (26%) ATBF-confirmed patients were seronegative (acute and convalescent-phase sera) against R africae; 14 had received doxycycline during the first week of clinical signs. The current hypothesis is that R africae is highly sensitive to doxycycline and that early exposure to the drug prevented development of detectable titers of reactive antibodies, thus producing a negative serology test.¹¹

Furthermore, it has been shown that seroconversion of IgG and IgM antibodies in R africae–infected sera is delayed compared to what is observed with R conorii–infected sera. Typically, seroconversion of R conorii–infected sera can be detected within 2 weeks; seroconversion in R africae–infected sera can take 4 weeks or longer.¹¹

Our patient had a confirmed case of ATBF secondary to R africae infection, which was evident from tissue culture isolation and polymerase chain reaction analysis of swab material obtained from eschar sites, both of which yielded a positive result for R africae. The traveler’s negative serologic status might be due to his early exposure to doxycycline or to the 4-week delay in R africae seroconversion; his serum was collected only 3 weeks after the tick bites.

Clinical signs also aid in making the diagnosis of ATBF and distinguishing R conorii from R africae infection. Because of the aggressive hunting nature of the tick carrying R africae, they are associated with multiple eschars and tend to affect groups of multiple people, especially in rural areas.^4,5 In contrast, ticks carrying R conorii yield a single eschar due to their passive style of infecting a host and because they favor a single host within urban areas.⁵ Both infections exhibit a maculopapular or papulovesicular rash and are accompanied by fatigue, headache, and myalgia, though ATBF tends to present with a milder rash than MSF.

Infection with either R conorii or R africae responds to tetracyclines, quinolones, and macrolides.^10,12

African tick-bite fever is becoming more common, which should encourage clinicians to become familiar with the disease. Less than 2 decades ago, ATBF virtually was unknown outside of Zimbabwe, Botswana, Tanzania, Zambia, and Kenya, where it is endemic. However, after the abolition of apartheid in the 1990s, international tourism in southern Africa increased 6-fold.¹³ African tick-bite fever is now one of the most common rickettsial infections in Africa.⁷ In addition to diagnosing ATBF and managing infected patients, clinicians can help prevent ATBF in individuals who travel to endemic areas by recommending commercial topical insect repellents containing at least 19.5% N,N-diethyl-meta-toluamide (DEET).¹⁴

To the Editor:

One of the more common tick-borne infections seen in travelers returning from sub-Saharan Africa is caused by Rickettsia africae, which is the etiologic agent of African tick-bite fever (ATBF), the most common tick-borne bacterial zoonosis.¹ There are 2 known tick vectors of disease: Amblyomma variegatum, found in sub-Saharan Africa and the West Indies, and Amblyomma hebraeum, found specifically in southern Africa.^2,3

Unlike other disease-carrying ticks that passively wait on vegetation to be picked up by a host, A hebraeum uniquely attract other nearby ticks to the host. Studies have shown that male ticks feeding on a nonhuman host (usually cattle) can emit an aggression-attachment pheromone that attracts other ticks to the host. The presence of the pheromone allows unfed ticks to actively discriminate between hosts on which these parasites have fed successfully (ie, suitable hosts) and those on which they have not.⁴

The aggressive hunting nature of A hebraeum explains the clinical presentation of multiple eschars and why large groups of exposed travelers—such as soldiers, leisure safari tourists, game hunters, and foreign-aid workers—are affected.²

Another southern African spotted fever group, Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF). Ticks carrying R conorii exhibit a much less aggressive hunting stylethan A hebraeum; consequently, infected patients present with a single eschar site.⁵

Rickettsia africae is estimated to have very high prevalence (95.2%) in Amblyomma ticks and a fairly high prevalence (approximately 4.0% to 8.6%) in travelers coming from rural southern Africa,^6,7 with an incubation period of 5 to 10 days after inoculation by an infected tick.⁸ Signs include fever, a generalized maculopapular or papulovesicular rash, and regional lymphadenopathy; symptoms include fatigue, headache, and myalgia.

The inoculation eschar—single or multiple—commonly presents on the legs and is accompanied by tender lymphadenopathy of draining nodes^1,8 More severe findings, such as myocarditis and subacute neuropathy, have been reported in elderly patients.⁹

A 77-year-old man presented with a pruritic maculopapular and papulovesicular rash distributed over the upper and lower extremities of 3 weeks’ duration. The patient reported having been on a 12-day mission trip to Limpopo, South Africa, where he was constructing and installing safe toilets to replace dangerous toilet pits. He believed he had been bitten by 2 ticks, after which he noted a dark purple and black patch on the left lower leg by the third day of the trip. He developed a sudden persistent pruritic rash, first on the lower extremities and then spreading to the upper extremities. The patient was seen by an American physician in South Africa who gave him a 7-day course of oral doxycycline monohydrate 100 mg twice daily. He then returned to the United States.

Sixteen days after being bitten by the ticks, the patient was examined in our dermatology office. Physical examination revealed an erythematous plaque with a central eschar over the medial aspect of the left leg (Figure 1) and multiple 3- to 6-mm, erythematous, dome-shaped papules scattered over the dorsal aspects of the feet and ankles (Figure 2). The examination was otherwise normal. Blood was drawn the same day for laboratory analysis; no abnormalities of platelets, red blood cells, or white blood cells were found. Results of a chemistry panel and liver enzyme tests were within reference range.

Skin biopsies were taken to elucidate the underlying pathology. Although an arthropod assault was suspected, there also was concern for deep vessel vasculitis because of the presence of considerable petechiae and purpura (Figure 3). Histologically, leukocytoclasia was seen in deep dermal blood vessels. A mild eosinophilic spongiosis with a mixed dermal infiltrate was identified—strengthening our suspicion of an arthropod assault. Bacterial cultures for aerobes and anaerobes using material taken from the right shin showed no growth.

Ten days after the initial biopsies, serum specimens were drawn and swabs of eschar were collected and sent to the Centers for Disease Control and Prevention for further testing. Serum was tested by immunofluorescence assay (IFA) for spotted fever group IgG to detect Rocky Mountain spotted fever and ATBF antibodies; both tests were negative. Swab material from eschar was tested again by IFA for spotted fever group IgG (Rocky Mountain spotted fever) and antibodies to ATBF and with bacterial culture isolation and nucleic acid amplification; the culture and amplification came back positive for R africae.

Because the specialized tests confirmed infection with R africae, the patient was given triamcinolone cream 0.1% to apply twice daily to the pruritic lesions for as long as 4 weeks; an additional 14-day course of oral doxycycline monohydrate (100 mg twice daily) was given. At follow-up, the lesions had fully resolved without evident scarring.

Various diagnostic techniques can detect R africae. Bacterial culture and the polymerase chain reaction are specific and therefore diagnostic. In addition, the diagnosis of rickettsiosis can be made with serology testing, in which disease-specific antibodies are detected by indirect IFA using disease-specific antigens.

Antigens from R rickettsii (the agent of Rocky Mountain spotted fever), R conorii (Mediterranean spotted fever), and R africae (ATBF) are commercially available for making the diagnosis of rickettsiosis. However, antigens from R conorii exhibit cross-reactivity with R africae, which can confound the diagnosis.^1,10 Serologic IFA tests have been shown to be less sensitive, especially when performed after antibacterial treatment has started.

In a study, 17 of 65 (26%) ATBF-confirmed patients were seronegative (acute and convalescent-phase sera) against R africae; 14 had received doxycycline during the first week of clinical signs. The current hypothesis is that R africae is highly sensitive to doxycycline and that early exposure to the drug prevented development of detectable titers of reactive antibodies, thus producing a negative serology test.¹¹

Furthermore, it has been shown that seroconversion of IgG and IgM antibodies in R africae–infected sera is delayed compared to what is observed with R conorii–infected sera. Typically, seroconversion of R conorii–infected sera can be detected within 2 weeks; seroconversion in R africae–infected sera can take 4 weeks or longer.¹¹

Our patient had a confirmed case of ATBF secondary to R africae infection, which was evident from tissue culture isolation and polymerase chain reaction analysis of swab material obtained from eschar sites, both of which yielded a positive result for R africae. The traveler’s negative serologic status might be due to his early exposure to doxycycline or to the 4-week delay in R africae seroconversion; his serum was collected only 3 weeks after the tick bites.

Clinical signs also aid in making the diagnosis of ATBF and distinguishing R conorii from R africae infection. Because of the aggressive hunting nature of the tick carrying R africae, they are associated with multiple eschars and tend to affect groups of multiple people, especially in rural areas.^4,5 In contrast, ticks carrying R conorii yield a single eschar due to their passive style of infecting a host and because they favor a single host within urban areas.⁵ Both infections exhibit a maculopapular or papulovesicular rash and are accompanied by fatigue, headache, and myalgia, though ATBF tends to present with a milder rash than MSF.

Infection with either R conorii or R africae responds to tetracyclines, quinolones, and macrolides.^10,12

African tick-bite fever is becoming more common, which should encourage clinicians to become familiar with the disease. Less than 2 decades ago, ATBF virtually was unknown outside of Zimbabwe, Botswana, Tanzania, Zambia, and Kenya, where it is endemic. However, after the abolition of apartheid in the 1990s, international tourism in southern Africa increased 6-fold.¹³ African tick-bite fever is now one of the most common rickettsial infections in Africa.⁷ In addition to diagnosing ATBF and managing infected patients, clinicians can help prevent ATBF in individuals who travel to endemic areas by recommending commercial topical insect repellents containing at least 19.5% N,N-diethyl-meta-toluamide (DEET).¹⁴

To the Editor:

One of the more common tick-borne infections seen in travelers returning from sub-Saharan Africa is caused by Rickettsia africae, which is the etiologic agent of African tick-bite fever (ATBF), the most common tick-borne bacterial zoonosis.¹ There are 2 known tick vectors of disease: Amblyomma variegatum, found in sub-Saharan Africa and the West Indies, and Amblyomma hebraeum, found specifically in southern Africa.^2,3

Unlike other disease-carrying ticks that passively wait on vegetation to be picked up by a host, A hebraeum uniquely attract other nearby ticks to the host. Studies have shown that male ticks feeding on a nonhuman host (usually cattle) can emit an aggression-attachment pheromone that attracts other ticks to the host. The presence of the pheromone allows unfed ticks to actively discriminate between hosts on which these parasites have fed successfully (ie, suitable hosts) and those on which they have not.⁴

The aggressive hunting nature of A hebraeum explains the clinical presentation of multiple eschars and why large groups of exposed travelers—such as soldiers, leisure safari tourists, game hunters, and foreign-aid workers—are affected.²

Another southern African spotted fever group, Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF). Ticks carrying R conorii exhibit a much less aggressive hunting stylethan A hebraeum; consequently, infected patients present with a single eschar site.⁵

Rickettsia africae is estimated to have very high prevalence (95.2%) in Amblyomma ticks and a fairly high prevalence (approximately 4.0% to 8.6%) in travelers coming from rural southern Africa,^6,7 with an incubation period of 5 to 10 days after inoculation by an infected tick.⁸ Signs include fever, a generalized maculopapular or papulovesicular rash, and regional lymphadenopathy; symptoms include fatigue, headache, and myalgia.

The inoculation eschar—single or multiple—commonly presents on the legs and is accompanied by tender lymphadenopathy of draining nodes^1,8 More severe findings, such as myocarditis and subacute neuropathy, have been reported in elderly patients.⁹

A 77-year-old man presented with a pruritic maculopapular and papulovesicular rash distributed over the upper and lower extremities of 3 weeks’ duration. The patient reported having been on a 12-day mission trip to Limpopo, South Africa, where he was constructing and installing safe toilets to replace dangerous toilet pits. He believed he had been bitten by 2 ticks, after which he noted a dark purple and black patch on the left lower leg by the third day of the trip. He developed a sudden persistent pruritic rash, first on the lower extremities and then spreading to the upper extremities. The patient was seen by an American physician in South Africa who gave him a 7-day course of oral doxycycline monohydrate 100 mg twice daily. He then returned to the United States.

Sixteen days after being bitten by the ticks, the patient was examined in our dermatology office. Physical examination revealed an erythematous plaque with a central eschar over the medial aspect of the left leg (Figure 1) and multiple 3- to 6-mm, erythematous, dome-shaped papules scattered over the dorsal aspects of the feet and ankles (Figure 2). The examination was otherwise normal. Blood was drawn the same day for laboratory analysis; no abnormalities of platelets, red blood cells, or white blood cells were found. Results of a chemistry panel and liver enzyme tests were within reference range.

Skin biopsies were taken to elucidate the underlying pathology. Although an arthropod assault was suspected, there also was concern for deep vessel vasculitis because of the presence of considerable petechiae and purpura (Figure 3). Histologically, leukocytoclasia was seen in deep dermal blood vessels. A mild eosinophilic spongiosis with a mixed dermal infiltrate was identified—strengthening our suspicion of an arthropod assault. Bacterial cultures for aerobes and anaerobes using material taken from the right shin showed no growth.

Ten days after the initial biopsies, serum specimens were drawn and swabs of eschar were collected and sent to the Centers for Disease Control and Prevention for further testing. Serum was tested by immunofluorescence assay (IFA) for spotted fever group IgG to detect Rocky Mountain spotted fever and ATBF antibodies; both tests were negative. Swab material from eschar was tested again by IFA for spotted fever group IgG (Rocky Mountain spotted fever) and antibodies to ATBF and with bacterial culture isolation and nucleic acid amplification; the culture and amplification came back positive for R africae.

Because the specialized tests confirmed infection with R africae, the patient was given triamcinolone cream 0.1% to apply twice daily to the pruritic lesions for as long as 4 weeks; an additional 14-day course of oral doxycycline monohydrate (100 mg twice daily) was given. At follow-up, the lesions had fully resolved without evident scarring.

Various diagnostic techniques can detect R africae. Bacterial culture and the polymerase chain reaction are specific and therefore diagnostic. In addition, the diagnosis of rickettsiosis can be made with serology testing, in which disease-specific antibodies are detected by indirect IFA using disease-specific antigens.

Antigens from R rickettsii (the agent of Rocky Mountain spotted fever), R conorii (Mediterranean spotted fever), and R africae (ATBF) are commercially available for making the diagnosis of rickettsiosis. However, antigens from R conorii exhibit cross-reactivity with R africae, which can confound the diagnosis.^1,10 Serologic IFA tests have been shown to be less sensitive, especially when performed after antibacterial treatment has started.

In a study, 17 of 65 (26%) ATBF-confirmed patients were seronegative (acute and convalescent-phase sera) against R africae; 14 had received doxycycline during the first week of clinical signs. The current hypothesis is that R africae is highly sensitive to doxycycline and that early exposure to the drug prevented development of detectable titers of reactive antibodies, thus producing a negative serology test.¹¹

Furthermore, it has been shown that seroconversion of IgG and IgM antibodies in R africae–infected sera is delayed compared to what is observed with R conorii–infected sera. Typically, seroconversion of R conorii–infected sera can be detected within 2 weeks; seroconversion in R africae–infected sera can take 4 weeks or longer.¹¹

Our patient had a confirmed case of ATBF secondary to R africae infection, which was evident from tissue culture isolation and polymerase chain reaction analysis of swab material obtained from eschar sites, both of which yielded a positive result for R africae. The traveler’s negative serologic status might be due to his early exposure to doxycycline or to the 4-week delay in R africae seroconversion; his serum was collected only 3 weeks after the tick bites.

Clinical signs also aid in making the diagnosis of ATBF and distinguishing R conorii from R africae infection. Because of the aggressive hunting nature of the tick carrying R africae, they are associated with multiple eschars and tend to affect groups of multiple people, especially in rural areas.^4,5 In contrast, ticks carrying R conorii yield a single eschar due to their passive style of infecting a host and because they favor a single host within urban areas.⁵ Both infections exhibit a maculopapular or papulovesicular rash and are accompanied by fatigue, headache, and myalgia, though ATBF tends to present with a milder rash than MSF.

Infection with either R conorii or R africae responds to tetracyclines, quinolones, and macrolides.^10,12

African tick-bite fever is becoming more common, which should encourage clinicians to become familiar with the disease. Less than 2 decades ago, ATBF virtually was unknown outside of Zimbabwe, Botswana, Tanzania, Zambia, and Kenya, where it is endemic. However, after the abolition of apartheid in the 1990s, international tourism in southern Africa increased 6-fold.¹³ African tick-bite fever is now one of the most common rickettsial infections in Africa.⁷ In addition to diagnosing ATBF and managing infected patients, clinicians can help prevent ATBF in individuals who travel to endemic areas by recommending commercial topical insect repellents containing at least 19.5% N,N-diethyl-meta-toluamide (DEET).¹⁴