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Multiply recurrent C. difficile infection is on the rise
A retrospective cohort study of Clostridium difficile infection (CDI), the most common health care–associated infection, found that multiply recurrent CDI (mrCDI) is increasing in incidence, disproportionately to the overall increase in CDI.
Researchers from the University of Pennsylvania, Philadelphia, worked with a database of more than 38 million individuals with private health insurance between January 2001 and December 2012.
Cases of CDI and mrCDI in the study population were determined through ICD-9 diagnosis codes, and prescriptions for treatment. To meet the definition of mrCDI, there had to be at least three courses of treatment lasting at least 14 days each.
In the study population, 45,341 persons developed CDI, of whom 1,669 had mrCDI. The median age was 46 years, and 58.9% were female. Between 2001 and 2012, CDI incidence increased by 42.7% (P = .004), while mrCDI incidence increased by 188.8% (P less than .001).
With increases in CDI and mrCDI incidence, and with the effectiveness of standard antibiotic treatment decreasing with each recurrence, “demand for new antimicrobial therapies and FMT [fecal microbiota transplantation] can be expected to increase considerably in the coming years,” wrote Gene K. Ma, MD, and his coauthors.
As for FMT, the researchers noted that its likely greater demand in the future (as suggested by their study results) highlights the importance of establishing the long-term safety of the procedure (Ann Intern Med. 2017 Jul. doi: 10.7326/M16-2733).
The retrospective cohort study was based on administrative data rather than laboratory data, Sameer D. Saini, MD, MS, and Akbar K. Waljee, MD, noted in an editorial accompanying the study. Further, with Medicare patients excluded from the study (because Medicare data were not available for the full time period studied for private insurance data), the data may not be of relevance to patients older than age 65 years.
But the general conclusion that both CDI and mrCDI are on the rise is a crucial matter. “We must first have a better understanding of mrCDI, its scope and epidemiology, and its associated risk factors. The study by Ma and colleagues begins this important work. A better understanding of the epidemiology of mrCDI is a critical first step toward developing a sound strategy to address this growing public health challenge.”
Dr. Saini and Dr. Waljee are with the VA Ann Arbor (Michigan) Center for Clinical Management. Their editorial accompanied the study in Annals of Internal Medicine (2017 Jul. doi: 10.7326/M17-1565).
The retrospective cohort study was based on administrative data rather than laboratory data, Sameer D. Saini, MD, MS, and Akbar K. Waljee, MD, noted in an editorial accompanying the study. Further, with Medicare patients excluded from the study (because Medicare data were not available for the full time period studied for private insurance data), the data may not be of relevance to patients older than age 65 years.
But the general conclusion that both CDI and mrCDI are on the rise is a crucial matter. “We must first have a better understanding of mrCDI, its scope and epidemiology, and its associated risk factors. The study by Ma and colleagues begins this important work. A better understanding of the epidemiology of mrCDI is a critical first step toward developing a sound strategy to address this growing public health challenge.”
Dr. Saini and Dr. Waljee are with the VA Ann Arbor (Michigan) Center for Clinical Management. Their editorial accompanied the study in Annals of Internal Medicine (2017 Jul. doi: 10.7326/M17-1565).
The retrospective cohort study was based on administrative data rather than laboratory data, Sameer D. Saini, MD, MS, and Akbar K. Waljee, MD, noted in an editorial accompanying the study. Further, with Medicare patients excluded from the study (because Medicare data were not available for the full time period studied for private insurance data), the data may not be of relevance to patients older than age 65 years.
But the general conclusion that both CDI and mrCDI are on the rise is a crucial matter. “We must first have a better understanding of mrCDI, its scope and epidemiology, and its associated risk factors. The study by Ma and colleagues begins this important work. A better understanding of the epidemiology of mrCDI is a critical first step toward developing a sound strategy to address this growing public health challenge.”
Dr. Saini and Dr. Waljee are with the VA Ann Arbor (Michigan) Center for Clinical Management. Their editorial accompanied the study in Annals of Internal Medicine (2017 Jul. doi: 10.7326/M17-1565).
A retrospective cohort study of Clostridium difficile infection (CDI), the most common health care–associated infection, found that multiply recurrent CDI (mrCDI) is increasing in incidence, disproportionately to the overall increase in CDI.
Researchers from the University of Pennsylvania, Philadelphia, worked with a database of more than 38 million individuals with private health insurance between January 2001 and December 2012.
Cases of CDI and mrCDI in the study population were determined through ICD-9 diagnosis codes, and prescriptions for treatment. To meet the definition of mrCDI, there had to be at least three courses of treatment lasting at least 14 days each.
In the study population, 45,341 persons developed CDI, of whom 1,669 had mrCDI. The median age was 46 years, and 58.9% were female. Between 2001 and 2012, CDI incidence increased by 42.7% (P = .004), while mrCDI incidence increased by 188.8% (P less than .001).
With increases in CDI and mrCDI incidence, and with the effectiveness of standard antibiotic treatment decreasing with each recurrence, “demand for new antimicrobial therapies and FMT [fecal microbiota transplantation] can be expected to increase considerably in the coming years,” wrote Gene K. Ma, MD, and his coauthors.
As for FMT, the researchers noted that its likely greater demand in the future (as suggested by their study results) highlights the importance of establishing the long-term safety of the procedure (Ann Intern Med. 2017 Jul. doi: 10.7326/M16-2733).
A retrospective cohort study of Clostridium difficile infection (CDI), the most common health care–associated infection, found that multiply recurrent CDI (mrCDI) is increasing in incidence, disproportionately to the overall increase in CDI.
Researchers from the University of Pennsylvania, Philadelphia, worked with a database of more than 38 million individuals with private health insurance between January 2001 and December 2012.
Cases of CDI and mrCDI in the study population were determined through ICD-9 diagnosis codes, and prescriptions for treatment. To meet the definition of mrCDI, there had to be at least three courses of treatment lasting at least 14 days each.
In the study population, 45,341 persons developed CDI, of whom 1,669 had mrCDI. The median age was 46 years, and 58.9% were female. Between 2001 and 2012, CDI incidence increased by 42.7% (P = .004), while mrCDI incidence increased by 188.8% (P less than .001).
With increases in CDI and mrCDI incidence, and with the effectiveness of standard antibiotic treatment decreasing with each recurrence, “demand for new antimicrobial therapies and FMT [fecal microbiota transplantation] can be expected to increase considerably in the coming years,” wrote Gene K. Ma, MD, and his coauthors.
As for FMT, the researchers noted that its likely greater demand in the future (as suggested by their study results) highlights the importance of establishing the long-term safety of the procedure (Ann Intern Med. 2017 Jul. doi: 10.7326/M16-2733).
FROM ANNALS OF INTERNAL MEDICINE
TB meningitis cases in U.S. are fewer but more complicated
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
BOSTON – The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.
However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.
The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”
According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.
TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.
For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).
Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.
“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”
However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).
• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).
• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).
• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.
Dr. Merkler said it’s not clear why these rates are going up, but it may be because patients have more complications as a result of living longer. Another theory is that a form of drug-resistant TB is boosting the level of these complications, Dr. Merkler said, but he’s skeptical of that idea: “I don’t know why drug resistance would lead to more neurological complications.”
The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
AT AAN 2017
Key clinical point:
Major finding: The rate of TB meningitis hospitalizations fell from 6.2 to 1.9 per million people (rate difference, 4.3; 95% CI, 2.1-6.5; P less than .001).
Data source: The Nationwide Inpatient Sample database, which revealed 16,196 new cases of TB meningitis from 1993 to 2013.
Disclosures: The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.
Bilateral cellulitis on legs? Think venous stasis dermatitis
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
SAN FRANCISCO – If a patient presents with bilateral cellulitis on both legs, think venous stasis dermatitis, which is the number one misdiagnosis of cellulitis and a frequent cause of unnecessary hospitalization for so-called “red leg,” according to Kanade Shinkai, MD, PhD.
“It’s easy to make that mistake, because you have a red, hot leg that’s painful, and the patient is having difficulty walking,” Dr. Shinkai said at the UCSF Annual Advances in Internal Medicine meeting. “Venous stasis dermatitis is one of the things you want to learn to recognize, as hospitalization is typically not needed.”
“That has to do with the venous return back to the heart,” said Dr. Shinkai, a dermatologist at UCSF Medical Center. “If it’s unilateral, it’s almost always on the left side.”
Patients often have features of venous insufficiency that cause stasis, including varicose veins and brawny hyperpigmentation on the medial aspects of the ankles. “They have almost no systemic features: no fever, no white count, no lymphadenopathy,” she said. “These patients need some kind of anti-inflammatory medication because the skin is very inflamed. If you happened to take a biopsy, you would see inflammation as well as lymphatic congestion.”
Dr. Shinkai recommends that patients apply a midpotency topical steroid such as triamcinolone to the affected area, followed by compression, ideally antiembolism stockings (TED hose) – but that can be a hard sell.
“When your legs are that swollen, they’re really painful to wear,” she said. “Patients will say, ‘Don’t you come near me with those TED hose.’ If you’re in that situation, tell them to use an Ace wrap with light compression and each day tighten the Ace wrap a little more until they are able to use TED hose with minimal discomfort.”
The differential diagnosis for venous stasis dermatitis includes cellulitis (which rarely presents bilaterally), deep vein thrombosis, asteatotic dermatitis, erysipelas (more superficial cellulitis that results in elevated, shiny plaques), pyomyositis, necrotizing fasciitis, leukocytoclastic vasculitis, and allergic contact dermatitis.
Dr. Shinkai reported having no relevant financial disclosures.
AT THE ANNUAL ADVANCES IN INTERNAL MEDICINE
U.S. malaria cases dipped slightly in 2014
The number of confirmed malaria cases reported in the United States in 2014 is the fourth highest annual total since 1973, according to the Centers for Disease Control and Prevention, but the 2014 number of 1,724 cases is down slightly from 1,741 – the previous year’s number of confirmed cases.
The CDC monitors malaria cases in part to identify any instances of local, rather than imported, transmission. For 2014, no cases of local transmission were reported.
Of the imported transmission cases for which the region of acquisition was known, 1,383 (82.1%) came from Africa and 160 (9.5%) from Asia, making up all but 62 of the imported cases. The four leading countries of origin in Africa were Nigeria, Ghana, Sierra Leone, and Liberia (346, 153, 133, and 125 cases, respectively). Most of the cases from Asia came from India, which accounted for 100 of the 160 cases.
Sierra Leone, Liberia, and Guinea were the countries primarily affected by the Ebola virus disease outbreak in 2014 and into 2015. The study authors, Kimberly E. Mace, PhD, and Paul M. Arguin, MD, noted in the May 26 Morbidity and Mortality Weekly Report that “Ebola negatively impacted the delivery of malaria care and prevention services in the Ebola-affected countries, which could have increased malaria morbidity and mortality” (MMWR Surveill Summ. 2017;66[12]:1-24).
“Despite progress in reducing global prevalence of malaria, the disease remains endemic in many regions and use of appropriate prevention measures by travelers is still inadequate,” they added.
Among all cases, 17% were classified as severe illness, including five deaths (a decrease from 10 deaths in 2013). All five patients who died reported not taking chemoprophylaxis during their travel. More than half (57.5%) of the patients reported that the purpose of their travel was to visit friends and relatives.
“Health care providers should talk to their patients, especially those who would travel to countries where malaria is endemic to visit friends and relatives, about upcoming travel plans and offer education and medicines to prevent malaria,” the authors wrote.
The number of confirmed malaria cases reported in the United States in 2014 is the fourth highest annual total since 1973, according to the Centers for Disease Control and Prevention, but the 2014 number of 1,724 cases is down slightly from 1,741 – the previous year’s number of confirmed cases.
The CDC monitors malaria cases in part to identify any instances of local, rather than imported, transmission. For 2014, no cases of local transmission were reported.
Of the imported transmission cases for which the region of acquisition was known, 1,383 (82.1%) came from Africa and 160 (9.5%) from Asia, making up all but 62 of the imported cases. The four leading countries of origin in Africa were Nigeria, Ghana, Sierra Leone, and Liberia (346, 153, 133, and 125 cases, respectively). Most of the cases from Asia came from India, which accounted for 100 of the 160 cases.
Sierra Leone, Liberia, and Guinea were the countries primarily affected by the Ebola virus disease outbreak in 2014 and into 2015. The study authors, Kimberly E. Mace, PhD, and Paul M. Arguin, MD, noted in the May 26 Morbidity and Mortality Weekly Report that “Ebola negatively impacted the delivery of malaria care and prevention services in the Ebola-affected countries, which could have increased malaria morbidity and mortality” (MMWR Surveill Summ. 2017;66[12]:1-24).
“Despite progress in reducing global prevalence of malaria, the disease remains endemic in many regions and use of appropriate prevention measures by travelers is still inadequate,” they added.
Among all cases, 17% were classified as severe illness, including five deaths (a decrease from 10 deaths in 2013). All five patients who died reported not taking chemoprophylaxis during their travel. More than half (57.5%) of the patients reported that the purpose of their travel was to visit friends and relatives.
“Health care providers should talk to their patients, especially those who would travel to countries where malaria is endemic to visit friends and relatives, about upcoming travel plans and offer education and medicines to prevent malaria,” the authors wrote.
The number of confirmed malaria cases reported in the United States in 2014 is the fourth highest annual total since 1973, according to the Centers for Disease Control and Prevention, but the 2014 number of 1,724 cases is down slightly from 1,741 – the previous year’s number of confirmed cases.
The CDC monitors malaria cases in part to identify any instances of local, rather than imported, transmission. For 2014, no cases of local transmission were reported.
Of the imported transmission cases for which the region of acquisition was known, 1,383 (82.1%) came from Africa and 160 (9.5%) from Asia, making up all but 62 of the imported cases. The four leading countries of origin in Africa were Nigeria, Ghana, Sierra Leone, and Liberia (346, 153, 133, and 125 cases, respectively). Most of the cases from Asia came from India, which accounted for 100 of the 160 cases.
Sierra Leone, Liberia, and Guinea were the countries primarily affected by the Ebola virus disease outbreak in 2014 and into 2015. The study authors, Kimberly E. Mace, PhD, and Paul M. Arguin, MD, noted in the May 26 Morbidity and Mortality Weekly Report that “Ebola negatively impacted the delivery of malaria care and prevention services in the Ebola-affected countries, which could have increased malaria morbidity and mortality” (MMWR Surveill Summ. 2017;66[12]:1-24).
“Despite progress in reducing global prevalence of malaria, the disease remains endemic in many regions and use of appropriate prevention measures by travelers is still inadequate,” they added.
Among all cases, 17% were classified as severe illness, including five deaths (a decrease from 10 deaths in 2013). All five patients who died reported not taking chemoprophylaxis during their travel. More than half (57.5%) of the patients reported that the purpose of their travel was to visit friends and relatives.
“Health care providers should talk to their patients, especially those who would travel to countries where malaria is endemic to visit friends and relatives, about upcoming travel plans and offer education and medicines to prevent malaria,” the authors wrote.
FROM MMWR
U.S. Zika epidemic could cost billions, or less
A Zika virus epidemic could cost the United States $183 million … or $680 million … or $2.2 billion, according to a new computational model developed to estimate Zika’s economic impact.
The model’s seeming lack of conviction comes from its options for an attack rate – the percentage of the population infected by the virus. An epidemic with a low attack rate of 0.01% would be expected to result in over 7,000 symptomatic cases and cost $183 million in direct medical costs and losses in productivity, said Bruce Y. Lee, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates (PLoS Negl Trop Dis. 2017 Apr 27;11[4]:e0005531).
The investigators based their model on the six states at the highest risk for local Zika emergence: Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas. The hypothetical epidemic lasts 230 days, which is equivalent to the Zika-related microcephaly outbreak in Brazil in 2015.
The National Institutes of Health, the Agency for Healthcare Research and Quality, and the United States Agency for International Development funded the study. The authors declared that no competing interests exist.
A Zika virus epidemic could cost the United States $183 million … or $680 million … or $2.2 billion, according to a new computational model developed to estimate Zika’s economic impact.
The model’s seeming lack of conviction comes from its options for an attack rate – the percentage of the population infected by the virus. An epidemic with a low attack rate of 0.01% would be expected to result in over 7,000 symptomatic cases and cost $183 million in direct medical costs and losses in productivity, said Bruce Y. Lee, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates (PLoS Negl Trop Dis. 2017 Apr 27;11[4]:e0005531).
The investigators based their model on the six states at the highest risk for local Zika emergence: Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas. The hypothetical epidemic lasts 230 days, which is equivalent to the Zika-related microcephaly outbreak in Brazil in 2015.
The National Institutes of Health, the Agency for Healthcare Research and Quality, and the United States Agency for International Development funded the study. The authors declared that no competing interests exist.
A Zika virus epidemic could cost the United States $183 million … or $680 million … or $2.2 billion, according to a new computational model developed to estimate Zika’s economic impact.
The model’s seeming lack of conviction comes from its options for an attack rate – the percentage of the population infected by the virus. An epidemic with a low attack rate of 0.01% would be expected to result in over 7,000 symptomatic cases and cost $183 million in direct medical costs and losses in productivity, said Bruce Y. Lee, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates (PLoS Negl Trop Dis. 2017 Apr 27;11[4]:e0005531).
The investigators based their model on the six states at the highest risk for local Zika emergence: Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas. The hypothetical epidemic lasts 230 days, which is equivalent to the Zika-related microcephaly outbreak in Brazil in 2015.
The National Institutes of Health, the Agency for Healthcare Research and Quality, and the United States Agency for International Development funded the study. The authors declared that no competing interests exist.
FROM PLOS NEGLECTED TROPICAL DISEASES
After the epidemic, Ebola’s destructive power still haunts survivors
VIENNA – The Ebola crisis may be over in Sierra Leone, but the suffering is not.
The last patient from the epidemic was discharged in February 2016, but 78% of survivors now appear to have one or more sequelae of the infection. Some problems are mild, but some are so debilitating that life may never be the same.
Janet Scott, MD, of the University of Liverpool (England), heads a task force studying Ebola’s lingering aftereffects. These fall into four categories, Dr. Scott said at the European Society of Clinical Microbiology and Infectious Diseases annual congress: musculoskeletal pain, headache, eye problems, and psychological disorders.
They add up to an enormous risk of disability – survivors are more than 200 times more likely than controls to express at least moderate disability.
Dr. Scott and her team of researchers are partnering with clinicians and data managers in the Ebola treatment unit in the 34th Regimental Military Hospital (MH34) in Freetown, Sierra Leone. In Sierra Leone alone, she said, there were nearly 9,000 cases and 3,500 deaths from the virus; about 5,000 patients survived. So far, Dr. Scott and her team have collected data on about 500 patients for whom they also provide free health care.
The project has six arms, each headed by an expert: clinical care, data collection, disability, neurology, ophthalmology, and psychiatry.
The team sees patients in a large tent sectioned by a plywood wall*. Wireless Internet access, which she said is “enormously expensive” in Sierra Leone, has been donated by Omline Business Communications*. It’s the team’s lifeline, allowing them to transmit data between Freetown and participating units around the world. Members also Skype regularly, talking with patients and with each other.
All patients who come into the clinic have an initial visit that includes collection of demographics, their Ebola and clinical history (including an exploration of comorbidities), a maternal health screening for women, vital signs and symptom assessment, medication dispensing, and a treatment plan.
Then they visit the specialists, either onsite or through local referral*. These specialist modules include joints, eyes, headache, ears, neurology, cardiac, respiratory, gastrointestinal, renal and urologic, reproductive health for both genders, and psychiatry.
Last year, Dr. Scott published initial data on 44 patients. At ECCMID 2017, she expanded that report to include 203 survivors. They spanned all ages, but about 67% were in their most productive adult years, aged 20-39 years.
Her findings are striking: About 78% report musculoskeletal pain, with many saying they have trouble walking even short distances, climbing stairs, or picking up their children.
Headache was the next most common problem, reported by nearly 40%. About 15% report ocular problems, which include anterior uveitis, cataracts – even in very young children – and retinal lesions. Abdominal and chest pain affect about 10% of the survivors.
Although she didn’t present specific numbers, Dr. Scott also said that many of the survivors experience psychological sequelae, including insomnia, anxiety, and depression. Whether this is related to viral pathology isn’t clear; it could be a not-unexpected response to the trauma of living through the epidemic.
“Many of these people have lost their entire family, and those that are left now shun them,” she said in a live video interview on Facebook. “It’s almost like a post-traumatic stress reaction.”
The other symptoms probably are related to the disease pathology, she observed. “Unfortunately, we don’t have all the clinical details of the acute phase for everyone, but for those for whom we do have details, we are seeing correlation between some of the problems with viral loads at admission, and even episodes of becoming unconscious during the acute illness.”
Patrick Howlett, MD, of the King’s Sierra Leone Partnership, Freetown, leads the neurology study. So far, the researchers have collected data on 19 patients with severe neurological consequences. Of those, 12 (63%) experienced a period of unconsciousness during their acute Ebola episode. In a comparator group of 21 with nonsevere neurologic sequelae, 33% had experienced unconsciousness.
Headache was present in nine (47%) of the patients. Migraine was the most common diagnosis. “We don’t have money for migraine medications, but fortunately, most of our migraine patients seem to be doing well on beta blockers,” Dr. Scott said.
CT scans were performed on 17 patients: three showed cerebral or cerebellar atrophy and two had confirmed stroke.
The brain injuries were severe in two, including a 42-year-old with extensive gliosis in the left middle cerebral artery region and a dilated left ventricle secondary to loss of volume in that hemisphere. A 12-year-old girl showed extensive parietal and temporal lobe atrophy. She is now so disabled that her family can’t care for her at home.
Other neurological problems include peripheral neuropathy, brachial plexus neuropathy, and asymmetric lower limb muscular atrophy.
Paul Steptoe, MD, an ophthalmic registrar from St. Paul’s Eye Unit at the Royal Liverpool Hospital, heads the eye study. He has observed dense cataracts, even in children, and anterior uveitis that has blinded some patients. There is concern about live virus persisting in vitreal fluid, but two eye taps have been negative, Dr. Scott said.
The most exciting recent finding, however, was made possible by the donation of a digital retinal camera, which “enabled us to get dozens of amazing images,” Dr. Scott said. With it, Dr. Steptoe conducted a case-control study of 81 Ebola survivors and 106 community controls. The findings of this study are potentially very, very important, Dr. Scott said.
“The first thing we found out is that retinal scarring is pervasive in our control patients,” she said. “There is just a lot of it out here in the community. But more interesting is that Dr. Steptoe seems to have identified a characteristic retinal lesion seen only in our survivors. It could be evidence of neurotropic aspects of the Ebola virus.”
The lesions occurred in 12 (15%) of the survivors and none of the controls. They are of a striking and consistent shape: straight-edged and sharply angulated. The lesions are only on the surface of the retina and do not penetrate into deeper levels. Nor do they interfere with vision. Dr. Steptoe has proposed that they take their angular shape from the retina’s underlying structures. His paper documenting this finding has been accepted and will be published shortly in the journal Emerging Infectious Diseases.
All of the post-Ebola sequelae add up to general disability for survivors, Dr. Scott said. Soushieta Jagadesh, of the* Liverpool School of Tropical Medicine, is conducting a disability survey. The comparison between 27 survivors and 54 community controls employed the Washington Group extended disability questionnaire. “We noted major limitations 1 year after discharge in mobility, vision, cognition, and affect,” Dr. Scott said.
The hazard ratios for these issues are enormous: Overall, compared with controls, survivors were 23 times more likely to have some level of disability. They were 94 times more likely to have walking limitations and 65 times more likely to have problems with stairs. Survivors were over 200 times more likely to have moderate disability than were their unaffected neighbors.
If funding for the project is renewed – and Dr. Scott admitted this is an “if,” not a “when” – caring for and studying these survivors will continue. Just in this one city, she said, the need is huge.
According to data from the U.S. Centers for Disease Control and Prevention, more than 17,000 patients in Sierra Leone, Liberia, and Guinea survived the 2014 Ebola outbreak.
If the assessments of Freetown survivors hold true across this population, thousands of survivors face life-limiting sequelae of the disease.
“We still have patients walk in every day with musculoskeletal pain, headaches, and ocular issues,” Dr. Scott said. “At the beginning of the epidemic, we were just focusing on containing it and reducing transmission. Now, we are faced with the long-term consequences.”
The Wellcome Trust supported the study. The authors have been awarded a grant from the Enhancing Research Activity in Epidemic Situations (ERAES) program, funded by the Wellcome Trust to support further research into the sequelae of Ebola virus disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_gal
*This story was updated May 2, 2017.
VIENNA – The Ebola crisis may be over in Sierra Leone, but the suffering is not.
The last patient from the epidemic was discharged in February 2016, but 78% of survivors now appear to have one or more sequelae of the infection. Some problems are mild, but some are so debilitating that life may never be the same.
Janet Scott, MD, of the University of Liverpool (England), heads a task force studying Ebola’s lingering aftereffects. These fall into four categories, Dr. Scott said at the European Society of Clinical Microbiology and Infectious Diseases annual congress: musculoskeletal pain, headache, eye problems, and psychological disorders.
They add up to an enormous risk of disability – survivors are more than 200 times more likely than controls to express at least moderate disability.
Dr. Scott and her team of researchers are partnering with clinicians and data managers in the Ebola treatment unit in the 34th Regimental Military Hospital (MH34) in Freetown, Sierra Leone. In Sierra Leone alone, she said, there were nearly 9,000 cases and 3,500 deaths from the virus; about 5,000 patients survived. So far, Dr. Scott and her team have collected data on about 500 patients for whom they also provide free health care.
The project has six arms, each headed by an expert: clinical care, data collection, disability, neurology, ophthalmology, and psychiatry.
The team sees patients in a large tent sectioned by a plywood wall*. Wireless Internet access, which she said is “enormously expensive” in Sierra Leone, has been donated by Omline Business Communications*. It’s the team’s lifeline, allowing them to transmit data between Freetown and participating units around the world. Members also Skype regularly, talking with patients and with each other.
All patients who come into the clinic have an initial visit that includes collection of demographics, their Ebola and clinical history (including an exploration of comorbidities), a maternal health screening for women, vital signs and symptom assessment, medication dispensing, and a treatment plan.
Then they visit the specialists, either onsite or through local referral*. These specialist modules include joints, eyes, headache, ears, neurology, cardiac, respiratory, gastrointestinal, renal and urologic, reproductive health for both genders, and psychiatry.
Last year, Dr. Scott published initial data on 44 patients. At ECCMID 2017, she expanded that report to include 203 survivors. They spanned all ages, but about 67% were in their most productive adult years, aged 20-39 years.
Her findings are striking: About 78% report musculoskeletal pain, with many saying they have trouble walking even short distances, climbing stairs, or picking up their children.
Headache was the next most common problem, reported by nearly 40%. About 15% report ocular problems, which include anterior uveitis, cataracts – even in very young children – and retinal lesions. Abdominal and chest pain affect about 10% of the survivors.
Although she didn’t present specific numbers, Dr. Scott also said that many of the survivors experience psychological sequelae, including insomnia, anxiety, and depression. Whether this is related to viral pathology isn’t clear; it could be a not-unexpected response to the trauma of living through the epidemic.
“Many of these people have lost their entire family, and those that are left now shun them,” she said in a live video interview on Facebook. “It’s almost like a post-traumatic stress reaction.”
The other symptoms probably are related to the disease pathology, she observed. “Unfortunately, we don’t have all the clinical details of the acute phase for everyone, but for those for whom we do have details, we are seeing correlation between some of the problems with viral loads at admission, and even episodes of becoming unconscious during the acute illness.”
Patrick Howlett, MD, of the King’s Sierra Leone Partnership, Freetown, leads the neurology study. So far, the researchers have collected data on 19 patients with severe neurological consequences. Of those, 12 (63%) experienced a period of unconsciousness during their acute Ebola episode. In a comparator group of 21 with nonsevere neurologic sequelae, 33% had experienced unconsciousness.
Headache was present in nine (47%) of the patients. Migraine was the most common diagnosis. “We don’t have money for migraine medications, but fortunately, most of our migraine patients seem to be doing well on beta blockers,” Dr. Scott said.
CT scans were performed on 17 patients: three showed cerebral or cerebellar atrophy and two had confirmed stroke.
The brain injuries were severe in two, including a 42-year-old with extensive gliosis in the left middle cerebral artery region and a dilated left ventricle secondary to loss of volume in that hemisphere. A 12-year-old girl showed extensive parietal and temporal lobe atrophy. She is now so disabled that her family can’t care for her at home.
Other neurological problems include peripheral neuropathy, brachial plexus neuropathy, and asymmetric lower limb muscular atrophy.
Paul Steptoe, MD, an ophthalmic registrar from St. Paul’s Eye Unit at the Royal Liverpool Hospital, heads the eye study. He has observed dense cataracts, even in children, and anterior uveitis that has blinded some patients. There is concern about live virus persisting in vitreal fluid, but two eye taps have been negative, Dr. Scott said.
The most exciting recent finding, however, was made possible by the donation of a digital retinal camera, which “enabled us to get dozens of amazing images,” Dr. Scott said. With it, Dr. Steptoe conducted a case-control study of 81 Ebola survivors and 106 community controls. The findings of this study are potentially very, very important, Dr. Scott said.
“The first thing we found out is that retinal scarring is pervasive in our control patients,” she said. “There is just a lot of it out here in the community. But more interesting is that Dr. Steptoe seems to have identified a characteristic retinal lesion seen only in our survivors. It could be evidence of neurotropic aspects of the Ebola virus.”
The lesions occurred in 12 (15%) of the survivors and none of the controls. They are of a striking and consistent shape: straight-edged and sharply angulated. The lesions are only on the surface of the retina and do not penetrate into deeper levels. Nor do they interfere with vision. Dr. Steptoe has proposed that they take their angular shape from the retina’s underlying structures. His paper documenting this finding has been accepted and will be published shortly in the journal Emerging Infectious Diseases.
All of the post-Ebola sequelae add up to general disability for survivors, Dr. Scott said. Soushieta Jagadesh, of the* Liverpool School of Tropical Medicine, is conducting a disability survey. The comparison between 27 survivors and 54 community controls employed the Washington Group extended disability questionnaire. “We noted major limitations 1 year after discharge in mobility, vision, cognition, and affect,” Dr. Scott said.
The hazard ratios for these issues are enormous: Overall, compared with controls, survivors were 23 times more likely to have some level of disability. They were 94 times more likely to have walking limitations and 65 times more likely to have problems with stairs. Survivors were over 200 times more likely to have moderate disability than were their unaffected neighbors.
If funding for the project is renewed – and Dr. Scott admitted this is an “if,” not a “when” – caring for and studying these survivors will continue. Just in this one city, she said, the need is huge.
According to data from the U.S. Centers for Disease Control and Prevention, more than 17,000 patients in Sierra Leone, Liberia, and Guinea survived the 2014 Ebola outbreak.
If the assessments of Freetown survivors hold true across this population, thousands of survivors face life-limiting sequelae of the disease.
“We still have patients walk in every day with musculoskeletal pain, headaches, and ocular issues,” Dr. Scott said. “At the beginning of the epidemic, we were just focusing on containing it and reducing transmission. Now, we are faced with the long-term consequences.”
The Wellcome Trust supported the study. The authors have been awarded a grant from the Enhancing Research Activity in Epidemic Situations (ERAES) program, funded by the Wellcome Trust to support further research into the sequelae of Ebola virus disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_gal
*This story was updated May 2, 2017.
VIENNA – The Ebola crisis may be over in Sierra Leone, but the suffering is not.
The last patient from the epidemic was discharged in February 2016, but 78% of survivors now appear to have one or more sequelae of the infection. Some problems are mild, but some are so debilitating that life may never be the same.
Janet Scott, MD, of the University of Liverpool (England), heads a task force studying Ebola’s lingering aftereffects. These fall into four categories, Dr. Scott said at the European Society of Clinical Microbiology and Infectious Diseases annual congress: musculoskeletal pain, headache, eye problems, and psychological disorders.
They add up to an enormous risk of disability – survivors are more than 200 times more likely than controls to express at least moderate disability.
Dr. Scott and her team of researchers are partnering with clinicians and data managers in the Ebola treatment unit in the 34th Regimental Military Hospital (MH34) in Freetown, Sierra Leone. In Sierra Leone alone, she said, there were nearly 9,000 cases and 3,500 deaths from the virus; about 5,000 patients survived. So far, Dr. Scott and her team have collected data on about 500 patients for whom they also provide free health care.
The project has six arms, each headed by an expert: clinical care, data collection, disability, neurology, ophthalmology, and psychiatry.
The team sees patients in a large tent sectioned by a plywood wall*. Wireless Internet access, which she said is “enormously expensive” in Sierra Leone, has been donated by Omline Business Communications*. It’s the team’s lifeline, allowing them to transmit data between Freetown and participating units around the world. Members also Skype regularly, talking with patients and with each other.
All patients who come into the clinic have an initial visit that includes collection of demographics, their Ebola and clinical history (including an exploration of comorbidities), a maternal health screening for women, vital signs and symptom assessment, medication dispensing, and a treatment plan.
Then they visit the specialists, either onsite or through local referral*. These specialist modules include joints, eyes, headache, ears, neurology, cardiac, respiratory, gastrointestinal, renal and urologic, reproductive health for both genders, and psychiatry.
Last year, Dr. Scott published initial data on 44 patients. At ECCMID 2017, she expanded that report to include 203 survivors. They spanned all ages, but about 67% were in their most productive adult years, aged 20-39 years.
Her findings are striking: About 78% report musculoskeletal pain, with many saying they have trouble walking even short distances, climbing stairs, or picking up their children.
Headache was the next most common problem, reported by nearly 40%. About 15% report ocular problems, which include anterior uveitis, cataracts – even in very young children – and retinal lesions. Abdominal and chest pain affect about 10% of the survivors.
Although she didn’t present specific numbers, Dr. Scott also said that many of the survivors experience psychological sequelae, including insomnia, anxiety, and depression. Whether this is related to viral pathology isn’t clear; it could be a not-unexpected response to the trauma of living through the epidemic.
“Many of these people have lost their entire family, and those that are left now shun them,” she said in a live video interview on Facebook. “It’s almost like a post-traumatic stress reaction.”
The other symptoms probably are related to the disease pathology, she observed. “Unfortunately, we don’t have all the clinical details of the acute phase for everyone, but for those for whom we do have details, we are seeing correlation between some of the problems with viral loads at admission, and even episodes of becoming unconscious during the acute illness.”
Patrick Howlett, MD, of the King’s Sierra Leone Partnership, Freetown, leads the neurology study. So far, the researchers have collected data on 19 patients with severe neurological consequences. Of those, 12 (63%) experienced a period of unconsciousness during their acute Ebola episode. In a comparator group of 21 with nonsevere neurologic sequelae, 33% had experienced unconsciousness.
Headache was present in nine (47%) of the patients. Migraine was the most common diagnosis. “We don’t have money for migraine medications, but fortunately, most of our migraine patients seem to be doing well on beta blockers,” Dr. Scott said.
CT scans were performed on 17 patients: three showed cerebral or cerebellar atrophy and two had confirmed stroke.
The brain injuries were severe in two, including a 42-year-old with extensive gliosis in the left middle cerebral artery region and a dilated left ventricle secondary to loss of volume in that hemisphere. A 12-year-old girl showed extensive parietal and temporal lobe atrophy. She is now so disabled that her family can’t care for her at home.
Other neurological problems include peripheral neuropathy, brachial plexus neuropathy, and asymmetric lower limb muscular atrophy.
Paul Steptoe, MD, an ophthalmic registrar from St. Paul’s Eye Unit at the Royal Liverpool Hospital, heads the eye study. He has observed dense cataracts, even in children, and anterior uveitis that has blinded some patients. There is concern about live virus persisting in vitreal fluid, but two eye taps have been negative, Dr. Scott said.
The most exciting recent finding, however, was made possible by the donation of a digital retinal camera, which “enabled us to get dozens of amazing images,” Dr. Scott said. With it, Dr. Steptoe conducted a case-control study of 81 Ebola survivors and 106 community controls. The findings of this study are potentially very, very important, Dr. Scott said.
“The first thing we found out is that retinal scarring is pervasive in our control patients,” she said. “There is just a lot of it out here in the community. But more interesting is that Dr. Steptoe seems to have identified a characteristic retinal lesion seen only in our survivors. It could be evidence of neurotropic aspects of the Ebola virus.”
The lesions occurred in 12 (15%) of the survivors and none of the controls. They are of a striking and consistent shape: straight-edged and sharply angulated. The lesions are only on the surface of the retina and do not penetrate into deeper levels. Nor do they interfere with vision. Dr. Steptoe has proposed that they take their angular shape from the retina’s underlying structures. His paper documenting this finding has been accepted and will be published shortly in the journal Emerging Infectious Diseases.
All of the post-Ebola sequelae add up to general disability for survivors, Dr. Scott said. Soushieta Jagadesh, of the* Liverpool School of Tropical Medicine, is conducting a disability survey. The comparison between 27 survivors and 54 community controls employed the Washington Group extended disability questionnaire. “We noted major limitations 1 year after discharge in mobility, vision, cognition, and affect,” Dr. Scott said.
The hazard ratios for these issues are enormous: Overall, compared with controls, survivors were 23 times more likely to have some level of disability. They were 94 times more likely to have walking limitations and 65 times more likely to have problems with stairs. Survivors were over 200 times more likely to have moderate disability than were their unaffected neighbors.
If funding for the project is renewed – and Dr. Scott admitted this is an “if,” not a “when” – caring for and studying these survivors will continue. Just in this one city, she said, the need is huge.
According to data from the U.S. Centers for Disease Control and Prevention, more than 17,000 patients in Sierra Leone, Liberia, and Guinea survived the 2014 Ebola outbreak.
If the assessments of Freetown survivors hold true across this population, thousands of survivors face life-limiting sequelae of the disease.
“We still have patients walk in every day with musculoskeletal pain, headaches, and ocular issues,” Dr. Scott said. “At the beginning of the epidemic, we were just focusing on containing it and reducing transmission. Now, we are faced with the long-term consequences.”
The Wellcome Trust supported the study. The authors have been awarded a grant from the Enhancing Research Activity in Epidemic Situations (ERAES) program, funded by the Wellcome Trust to support further research into the sequelae of Ebola virus disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_gal
*This story was updated May 2, 2017.
AT ECCMID 2017
A viral inducer of celiac disease?
A viral infection may be the culprit behind celiac disease, which is caused by an autoimmune response to dietary gluten. The findings are based on an engineered reovirus, which is normally benign. The researchers believe that a reovirus may disrupt intestinal immune homeostasis in susceptible individuals as a result of infection during childhood.
According to in vitro and mouse studies carried out by the researchers, one strain of reovirus suppresses peripheral regulatory T-cell conversion and promotes T helper 1 immune response at sites that normally induce tolerance to dietary antigens. The work appeared in the April issue of Science (2017;356:44-50).
The researchers decided to investigate reoviruses. They often infect humans, commonly in early childhood when gluten usually is first introduced. They also infect humans and mice similarly, allowing a more straightforward comparison between human and mouse studies than would be possible in other virus types.
The researchers created an engineered virus made from two reovirus strains, T1L and T3D, which naturally reassort in human hosts. T1L infects the intestine, while T3D does not. The new strain, T3D-RV, retains most of the characteristics of T3D but can also infect the intestine.
The researchers then conducted mouse studies and showed that both T1L and T3D-RV affect immune responses to dietary antigens at the inductive and effector sites of oral tolerance. However, the original T1L strain caused more changes in gene transcription, both in the number of genes and the intensity of transcription level. This suggested that T1L might uniquely alter immunogenic responses to dietary antigens.
A further test in mice showed that T1L also prompted a proinflammatory response in dendritic cells that take up ovalbumin, but T3D-RV did not. Furthermore, T1L interfered with induction of peripheral tolerance to oral ovalbumin, and T3D-RV did not.
With this data in hand, the researchers turned to human subjects. They compared 73 healthy controls to 160 patients with celiac disease who were on a gluten-free diet. Celiac disease patients had higher mean antireovirus antibody titers, though the result fell short of statistical significance (P = .06), and subjects with celiac disease were over-represented among subjects who had antireovirus titers above the median value.
“You can have two viruses of the same family infecting the intestine in the same way, inducing protective immunity, and being cleared, but only one sets the stage for disease. Finally, using these two viruses allows [us] to dissociate protective immunity from immunopathology. Only the virus that has the capacity to enter the site where dietary proteins are seen by the immune system can trigger disease,” said Bana Jabri, MD, PhD, professor of medicine at the University of Chicago.
Reovirus is unlikely to be the only, otherwise harmless, virus that could prompt wayward immune responses. The research points the way to the identification of viruses linked to celiac disease and other autoimmune diseases and could inform vaccine strategies to prevent such conditions.
The study received funding from the National Institutes of Health and the University of Chicago. No conflict of interest information was disclosed in the article.
A viral infection may be the culprit behind celiac disease, which is caused by an autoimmune response to dietary gluten. The findings are based on an engineered reovirus, which is normally benign. The researchers believe that a reovirus may disrupt intestinal immune homeostasis in susceptible individuals as a result of infection during childhood.
According to in vitro and mouse studies carried out by the researchers, one strain of reovirus suppresses peripheral regulatory T-cell conversion and promotes T helper 1 immune response at sites that normally induce tolerance to dietary antigens. The work appeared in the April issue of Science (2017;356:44-50).
The researchers decided to investigate reoviruses. They often infect humans, commonly in early childhood when gluten usually is first introduced. They also infect humans and mice similarly, allowing a more straightforward comparison between human and mouse studies than would be possible in other virus types.
The researchers created an engineered virus made from two reovirus strains, T1L and T3D, which naturally reassort in human hosts. T1L infects the intestine, while T3D does not. The new strain, T3D-RV, retains most of the characteristics of T3D but can also infect the intestine.
The researchers then conducted mouse studies and showed that both T1L and T3D-RV affect immune responses to dietary antigens at the inductive and effector sites of oral tolerance. However, the original T1L strain caused more changes in gene transcription, both in the number of genes and the intensity of transcription level. This suggested that T1L might uniquely alter immunogenic responses to dietary antigens.
A further test in mice showed that T1L also prompted a proinflammatory response in dendritic cells that take up ovalbumin, but T3D-RV did not. Furthermore, T1L interfered with induction of peripheral tolerance to oral ovalbumin, and T3D-RV did not.
With this data in hand, the researchers turned to human subjects. They compared 73 healthy controls to 160 patients with celiac disease who were on a gluten-free diet. Celiac disease patients had higher mean antireovirus antibody titers, though the result fell short of statistical significance (P = .06), and subjects with celiac disease were over-represented among subjects who had antireovirus titers above the median value.
“You can have two viruses of the same family infecting the intestine in the same way, inducing protective immunity, and being cleared, but only one sets the stage for disease. Finally, using these two viruses allows [us] to dissociate protective immunity from immunopathology. Only the virus that has the capacity to enter the site where dietary proteins are seen by the immune system can trigger disease,” said Bana Jabri, MD, PhD, professor of medicine at the University of Chicago.
Reovirus is unlikely to be the only, otherwise harmless, virus that could prompt wayward immune responses. The research points the way to the identification of viruses linked to celiac disease and other autoimmune diseases and could inform vaccine strategies to prevent such conditions.
The study received funding from the National Institutes of Health and the University of Chicago. No conflict of interest information was disclosed in the article.
A viral infection may be the culprit behind celiac disease, which is caused by an autoimmune response to dietary gluten. The findings are based on an engineered reovirus, which is normally benign. The researchers believe that a reovirus may disrupt intestinal immune homeostasis in susceptible individuals as a result of infection during childhood.
According to in vitro and mouse studies carried out by the researchers, one strain of reovirus suppresses peripheral regulatory T-cell conversion and promotes T helper 1 immune response at sites that normally induce tolerance to dietary antigens. The work appeared in the April issue of Science (2017;356:44-50).
The researchers decided to investigate reoviruses. They often infect humans, commonly in early childhood when gluten usually is first introduced. They also infect humans and mice similarly, allowing a more straightforward comparison between human and mouse studies than would be possible in other virus types.
The researchers created an engineered virus made from two reovirus strains, T1L and T3D, which naturally reassort in human hosts. T1L infects the intestine, while T3D does not. The new strain, T3D-RV, retains most of the characteristics of T3D but can also infect the intestine.
The researchers then conducted mouse studies and showed that both T1L and T3D-RV affect immune responses to dietary antigens at the inductive and effector sites of oral tolerance. However, the original T1L strain caused more changes in gene transcription, both in the number of genes and the intensity of transcription level. This suggested that T1L might uniquely alter immunogenic responses to dietary antigens.
A further test in mice showed that T1L also prompted a proinflammatory response in dendritic cells that take up ovalbumin, but T3D-RV did not. Furthermore, T1L interfered with induction of peripheral tolerance to oral ovalbumin, and T3D-RV did not.
With this data in hand, the researchers turned to human subjects. They compared 73 healthy controls to 160 patients with celiac disease who were on a gluten-free diet. Celiac disease patients had higher mean antireovirus antibody titers, though the result fell short of statistical significance (P = .06), and subjects with celiac disease were over-represented among subjects who had antireovirus titers above the median value.
“You can have two viruses of the same family infecting the intestine in the same way, inducing protective immunity, and being cleared, but only one sets the stage for disease. Finally, using these two viruses allows [us] to dissociate protective immunity from immunopathology. Only the virus that has the capacity to enter the site where dietary proteins are seen by the immune system can trigger disease,” said Bana Jabri, MD, PhD, professor of medicine at the University of Chicago.
Reovirus is unlikely to be the only, otherwise harmless, virus that could prompt wayward immune responses. The research points the way to the identification of viruses linked to celiac disease and other autoimmune diseases and could inform vaccine strategies to prevent such conditions.
The study received funding from the National Institutes of Health and the University of Chicago. No conflict of interest information was disclosed in the article.
FROM SCIENCE
Key clinical point: Celiac disease patients have high reovirus antibody titers.
Major finding: Researchers detail mechanistic pathway that could explain a viral link.
Data source: In vitro, human, and mouse observational studies.
Disclosures: The study received funding from the National Institutes of Health and the University of Chicago. No conflict of interest information was disclosed in the article.
Anthony Fauci faces the ‘perpetual challenge’ of emerging infections
SAN DIEGO – Reflecting on his 33-year career as director of the National Institute of Allergy and Infectious Diseases, Anthony S. Fauci, MD, can say one thing for certain: Emerging and re-emerging infectious diseases in the continental United States are here to stay.
In an article that he and his colleagues published in the Lancet in 2008, they used the term “perpetual challenge” to describe emerging infections, a descriptor that resonates with him to this day.
Global examples of emerging and re-emerging infectious diseases he discussed include dengue, West Nile virus, chikungunya, and carbapenem-resistant Enterobacteriaceae, “which is becoming a progressively more serious problem in hospitalized patients,” said Dr. Fauci, who is also chief of the NIAID Laboratory of Immunoregulation.
“We had a serious challenge with that at our own clinical center in Bethesda just a few years ago,” he noted. Numerous cases of antimicrobial resistance in methicillin-resistant Staphylococcus aureus, Clostridium difficile, and Neisseria gonorrhoeae have been reported.
Dr. Fauci described the Ebola outbreak as “a globally important disease that had ripple effects in the United States that were unpredicted,” referring to the case of the infected man who traveled from Monrovia to Dallas on Sept. 19, 2014, and developed Ebola symptoms 5 days later. Between 2014 and 2016, there were 28,616 cases and 11,310 deaths combined in the countries of Guinea, Sierra Leone, and Liberia.
“There is virtually no health care system in those three countries,” he said. “There’s a distrust in authority, and anything we tried to do as a global health [effort] made things worse. What we’re trying to do now is built sustainable health care issues in countries that don’t have it.”
Of particular concern to public health officials worldwide is getting a lid on Zika virus, a mosquito-borne illness that can be passed from a pregnant woman to her fetus and cause an increased risk of microcephaly, particularly during the first trimester.
“Not only is there microcephaly, there’s a whole host of abnormalities that involve hearing loss, visual abnormalities, and a variety of other issues,” Dr. Fauci said. “There are about 50 countries in the Americas and the Caribbean that have Zika virus transmission.”
According to data from the Centers for Disease Control and Prevention, from Jan. 1, 2015, to March 29, 2017, there were 5,182 reported cases of Zika virus disease in the 50 states and the District of Columbia. The majority of those (4,886) were travel associated, 222 were locally acquired mosquito-borne, 45 were sexually transmitted, 27 congenital, 1 was laboratory acquired, and 1 was unknown.
At the same time, there have been 38,303 cases in the U.S. territories. Of those, 38,156 were locally acquired, and 147 were travel associated. “That’s why there’s such an intense effort to develop a Zika vaccine,” he said.
According to the CDC, as of March 15, 2017, there are 265 cases of locally transmitted cases in Florida: 216 by mosquito and the rest by sexual transmission. “Talk about surprises,” Dr. Fauci said. “Zika is the first mosquito-borne infection that can result in a congenital abnormality, the first mosquito-borne infection that can be sexually transmitted, and now we’re learning more about this problem, which is the reason why it’s very important for us to develop a vaccine.”
A phase I trial of a DNA vaccine developed by the NIH Vaccine Research Center has reached its enrollment goal of 80 patients age 18-35 years. Initial results are expected sometime in the first quarter of 2017. A phase II trial in the United States and Puerto Rico is expected to launch soon.
Dr. Fauci closed his presentation by sharing lessons learned from previous pandemics.
The first lesson is that global surveillance is required. “Namely, know what’s going on in real time,” he said. “That has to be linked to transparency and communication. So that if something happens in China, we don’t find out about it months later, but we know about it in real time.”
Infrastructure and capacity building are also important. “The lack of capacity in West Africa can ultimately have an indirect impact on us here in the United States,” he said.
“Finally, we need to coordinate and collaborate; we need adaptable platforms for vaccines,” Dr. Fauci cautioned. “Importantly, we need a stable funding mechanism such as a public health emergency fund so that we do not have to go scrambling before the Congress when we need emergency funds.”
SAN DIEGO – Reflecting on his 33-year career as director of the National Institute of Allergy and Infectious Diseases, Anthony S. Fauci, MD, can say one thing for certain: Emerging and re-emerging infectious diseases in the continental United States are here to stay.
In an article that he and his colleagues published in the Lancet in 2008, they used the term “perpetual challenge” to describe emerging infections, a descriptor that resonates with him to this day.
Global examples of emerging and re-emerging infectious diseases he discussed include dengue, West Nile virus, chikungunya, and carbapenem-resistant Enterobacteriaceae, “which is becoming a progressively more serious problem in hospitalized patients,” said Dr. Fauci, who is also chief of the NIAID Laboratory of Immunoregulation.
“We had a serious challenge with that at our own clinical center in Bethesda just a few years ago,” he noted. Numerous cases of antimicrobial resistance in methicillin-resistant Staphylococcus aureus, Clostridium difficile, and Neisseria gonorrhoeae have been reported.
Dr. Fauci described the Ebola outbreak as “a globally important disease that had ripple effects in the United States that were unpredicted,” referring to the case of the infected man who traveled from Monrovia to Dallas on Sept. 19, 2014, and developed Ebola symptoms 5 days later. Between 2014 and 2016, there were 28,616 cases and 11,310 deaths combined in the countries of Guinea, Sierra Leone, and Liberia.
“There is virtually no health care system in those three countries,” he said. “There’s a distrust in authority, and anything we tried to do as a global health [effort] made things worse. What we’re trying to do now is built sustainable health care issues in countries that don’t have it.”
Of particular concern to public health officials worldwide is getting a lid on Zika virus, a mosquito-borne illness that can be passed from a pregnant woman to her fetus and cause an increased risk of microcephaly, particularly during the first trimester.
“Not only is there microcephaly, there’s a whole host of abnormalities that involve hearing loss, visual abnormalities, and a variety of other issues,” Dr. Fauci said. “There are about 50 countries in the Americas and the Caribbean that have Zika virus transmission.”
According to data from the Centers for Disease Control and Prevention, from Jan. 1, 2015, to March 29, 2017, there were 5,182 reported cases of Zika virus disease in the 50 states and the District of Columbia. The majority of those (4,886) were travel associated, 222 were locally acquired mosquito-borne, 45 were sexually transmitted, 27 congenital, 1 was laboratory acquired, and 1 was unknown.
At the same time, there have been 38,303 cases in the U.S. territories. Of those, 38,156 were locally acquired, and 147 were travel associated. “That’s why there’s such an intense effort to develop a Zika vaccine,” he said.
According to the CDC, as of March 15, 2017, there are 265 cases of locally transmitted cases in Florida: 216 by mosquito and the rest by sexual transmission. “Talk about surprises,” Dr. Fauci said. “Zika is the first mosquito-borne infection that can result in a congenital abnormality, the first mosquito-borne infection that can be sexually transmitted, and now we’re learning more about this problem, which is the reason why it’s very important for us to develop a vaccine.”
A phase I trial of a DNA vaccine developed by the NIH Vaccine Research Center has reached its enrollment goal of 80 patients age 18-35 years. Initial results are expected sometime in the first quarter of 2017. A phase II trial in the United States and Puerto Rico is expected to launch soon.
Dr. Fauci closed his presentation by sharing lessons learned from previous pandemics.
The first lesson is that global surveillance is required. “Namely, know what’s going on in real time,” he said. “That has to be linked to transparency and communication. So that if something happens in China, we don’t find out about it months later, but we know about it in real time.”
Infrastructure and capacity building are also important. “The lack of capacity in West Africa can ultimately have an indirect impact on us here in the United States,” he said.
“Finally, we need to coordinate and collaborate; we need adaptable platforms for vaccines,” Dr. Fauci cautioned. “Importantly, we need a stable funding mechanism such as a public health emergency fund so that we do not have to go scrambling before the Congress when we need emergency funds.”
SAN DIEGO – Reflecting on his 33-year career as director of the National Institute of Allergy and Infectious Diseases, Anthony S. Fauci, MD, can say one thing for certain: Emerging and re-emerging infectious diseases in the continental United States are here to stay.
In an article that he and his colleagues published in the Lancet in 2008, they used the term “perpetual challenge” to describe emerging infections, a descriptor that resonates with him to this day.
Global examples of emerging and re-emerging infectious diseases he discussed include dengue, West Nile virus, chikungunya, and carbapenem-resistant Enterobacteriaceae, “which is becoming a progressively more serious problem in hospitalized patients,” said Dr. Fauci, who is also chief of the NIAID Laboratory of Immunoregulation.
“We had a serious challenge with that at our own clinical center in Bethesda just a few years ago,” he noted. Numerous cases of antimicrobial resistance in methicillin-resistant Staphylococcus aureus, Clostridium difficile, and Neisseria gonorrhoeae have been reported.
Dr. Fauci described the Ebola outbreak as “a globally important disease that had ripple effects in the United States that were unpredicted,” referring to the case of the infected man who traveled from Monrovia to Dallas on Sept. 19, 2014, and developed Ebola symptoms 5 days later. Between 2014 and 2016, there were 28,616 cases and 11,310 deaths combined in the countries of Guinea, Sierra Leone, and Liberia.
“There is virtually no health care system in those three countries,” he said. “There’s a distrust in authority, and anything we tried to do as a global health [effort] made things worse. What we’re trying to do now is built sustainable health care issues in countries that don’t have it.”
Of particular concern to public health officials worldwide is getting a lid on Zika virus, a mosquito-borne illness that can be passed from a pregnant woman to her fetus and cause an increased risk of microcephaly, particularly during the first trimester.
“Not only is there microcephaly, there’s a whole host of abnormalities that involve hearing loss, visual abnormalities, and a variety of other issues,” Dr. Fauci said. “There are about 50 countries in the Americas and the Caribbean that have Zika virus transmission.”
According to data from the Centers for Disease Control and Prevention, from Jan. 1, 2015, to March 29, 2017, there were 5,182 reported cases of Zika virus disease in the 50 states and the District of Columbia. The majority of those (4,886) were travel associated, 222 were locally acquired mosquito-borne, 45 were sexually transmitted, 27 congenital, 1 was laboratory acquired, and 1 was unknown.
At the same time, there have been 38,303 cases in the U.S. territories. Of those, 38,156 were locally acquired, and 147 were travel associated. “That’s why there’s such an intense effort to develop a Zika vaccine,” he said.
According to the CDC, as of March 15, 2017, there are 265 cases of locally transmitted cases in Florida: 216 by mosquito and the rest by sexual transmission. “Talk about surprises,” Dr. Fauci said. “Zika is the first mosquito-borne infection that can result in a congenital abnormality, the first mosquito-borne infection that can be sexually transmitted, and now we’re learning more about this problem, which is the reason why it’s very important for us to develop a vaccine.”
A phase I trial of a DNA vaccine developed by the NIH Vaccine Research Center has reached its enrollment goal of 80 patients age 18-35 years. Initial results are expected sometime in the first quarter of 2017. A phase II trial in the United States and Puerto Rico is expected to launch soon.
Dr. Fauci closed his presentation by sharing lessons learned from previous pandemics.
The first lesson is that global surveillance is required. “Namely, know what’s going on in real time,” he said. “That has to be linked to transparency and communication. So that if something happens in China, we don’t find out about it months later, but we know about it in real time.”
Infrastructure and capacity building are also important. “The lack of capacity in West Africa can ultimately have an indirect impact on us here in the United States,” he said.
“Finally, we need to coordinate and collaborate; we need adaptable platforms for vaccines,” Dr. Fauci cautioned. “Importantly, we need a stable funding mechanism such as a public health emergency fund so that we do not have to go scrambling before the Congress when we need emergency funds.”
EXPERT ANALYSIS FROM ACP INTERNAL MEDICINE
Chikungunya arthritis symptoms reduced with immunomodulatory drugs
Several different currently approved immunomodulatory therapies ameliorated arthritis symptoms in chikungunya-infected mice in two studies that separate teams of researchers published online Feb. 1 in Science Translational Medicine.
The first team, led by Jonathan J. Miner, MD, PhD, of Washington University in St. Louis tested six different approved oral and biologic antirheumatic agents (along with control agents) in chikungunya virus-infected mice with acute arthritis and foot swelling (Sci Transl Med. 2017;9:eaah3438).
When the researchers paired abatacept with an antiviral therapy (monoclonal anti-CHIKV human antibody) the combination “was highly effective at reducing joint inflammation, periarticular swelling, migration of inflammatory leukocytes, and infection, even when administered several days after virus inoculation,” Dr. Miner and his colleagues wrote.
The researchers concluded that a combination of anti-inflammatory and antibody-based antiviral therapy “may serve as a model for treating humans with arthritis caused by CHIKV or other related viruses.”
In the second study, researchers led by Teck-Hui Teo, PhD, of the Agency for Science, Technology and Research (A*STAR) in Singapore, further elucidated the mechanisms by which CHIKV proteins act on T cells (Sci Transl Med. 2017;9:eaal1333). They also found that CHIKV-infected mice treated with fingolimod (Gilenya), a drug that blocks T-cell migration from the lymph nodes to the joints and is approved for the treatment of multiple sclerosis, saw reduced arthritis symptoms even without reduction of viral replication.
Infection with the chikungunya virus can produce arthritis that mimics symptoms of rheumatoid arthritis and may in some cases lead to joint damage. Though the mechanisms driving chikungunya-related arthritis are not well understood, preliminary studies have suggested a T-cell–mediated adverse response.
The Singapore team received funding from its own agency, A*STAR, while the Washington University researchers received grants from the National Institutes of Health and the Rheumatology Research Foundation. Two coauthors on the U.S. study reported extensive commercial conflicts, including consulting and advisory relationships with pharmaceutical and vaccine manufacturers, and one patent.
The studies by Dr. Miner and his colleagues and Dr. Teo and his associates demonstrate the potential value of combination therapies for ameliorating heightened T-cell responses and their pathogenic role in joint inflammation. They explored how T-cell responses could be blunted during ongoing viral replication to control overt inflammation, an approach that also may be valuable for treating immune-mediated tissue damage associated with other infectious agents.
Selective T-cell immunomodulatory therapies that offset damaging immune responses offer an attractive option for future pharmacologic interventions for treating chikungunya virus–induced inflammatory disease. The small market size and the rapid sporadic nature of outbreaks could be major obstacles to the development and deployment of virus-specific interventions such as therapeutic antiviral neutralizing monoclonal antibodies or even vaccines. Targeted drug and immunotherapy treatments are likely to offer practical and beneficial options for most patients with chikungunya.
Preliminary reports in humans have suggested that methotrexate may be effective for treating chikungunya virus–induced arthritis. In Dr. Miner and colleagues’ study, a low dose of methotrexate (0.3 mg/kg) was ineffective at treating acute joint swelling in mice. It remains to be addressed whether a higher dose of methotrexate for a longer time period could be of benefit in the setting of chronic chikungunya virus–induced arthritis.
Philippe Gasque, MD, PhD, is with the Université de La Réunion, Saint-Denis, Réunion, and Marie Christine Jaffar-Bandjee, MD, PhD, is with the Centre Hospitalier Universitaire Félix Guyon, Saint-Denis, Réunion. They made these remarks in an editorial (Sci Transl Med. 2017;9:eaam6567).
The studies by Dr. Miner and his colleagues and Dr. Teo and his associates demonstrate the potential value of combination therapies for ameliorating heightened T-cell responses and their pathogenic role in joint inflammation. They explored how T-cell responses could be blunted during ongoing viral replication to control overt inflammation, an approach that also may be valuable for treating immune-mediated tissue damage associated with other infectious agents.
Selective T-cell immunomodulatory therapies that offset damaging immune responses offer an attractive option for future pharmacologic interventions for treating chikungunya virus–induced inflammatory disease. The small market size and the rapid sporadic nature of outbreaks could be major obstacles to the development and deployment of virus-specific interventions such as therapeutic antiviral neutralizing monoclonal antibodies or even vaccines. Targeted drug and immunotherapy treatments are likely to offer practical and beneficial options for most patients with chikungunya.
Preliminary reports in humans have suggested that methotrexate may be effective for treating chikungunya virus–induced arthritis. In Dr. Miner and colleagues’ study, a low dose of methotrexate (0.3 mg/kg) was ineffective at treating acute joint swelling in mice. It remains to be addressed whether a higher dose of methotrexate for a longer time period could be of benefit in the setting of chronic chikungunya virus–induced arthritis.
Philippe Gasque, MD, PhD, is with the Université de La Réunion, Saint-Denis, Réunion, and Marie Christine Jaffar-Bandjee, MD, PhD, is with the Centre Hospitalier Universitaire Félix Guyon, Saint-Denis, Réunion. They made these remarks in an editorial (Sci Transl Med. 2017;9:eaam6567).
The studies by Dr. Miner and his colleagues and Dr. Teo and his associates demonstrate the potential value of combination therapies for ameliorating heightened T-cell responses and their pathogenic role in joint inflammation. They explored how T-cell responses could be blunted during ongoing viral replication to control overt inflammation, an approach that also may be valuable for treating immune-mediated tissue damage associated with other infectious agents.
Selective T-cell immunomodulatory therapies that offset damaging immune responses offer an attractive option for future pharmacologic interventions for treating chikungunya virus–induced inflammatory disease. The small market size and the rapid sporadic nature of outbreaks could be major obstacles to the development and deployment of virus-specific interventions such as therapeutic antiviral neutralizing monoclonal antibodies or even vaccines. Targeted drug and immunotherapy treatments are likely to offer practical and beneficial options for most patients with chikungunya.
Preliminary reports in humans have suggested that methotrexate may be effective for treating chikungunya virus–induced arthritis. In Dr. Miner and colleagues’ study, a low dose of methotrexate (0.3 mg/kg) was ineffective at treating acute joint swelling in mice. It remains to be addressed whether a higher dose of methotrexate for a longer time period could be of benefit in the setting of chronic chikungunya virus–induced arthritis.
Philippe Gasque, MD, PhD, is with the Université de La Réunion, Saint-Denis, Réunion, and Marie Christine Jaffar-Bandjee, MD, PhD, is with the Centre Hospitalier Universitaire Félix Guyon, Saint-Denis, Réunion. They made these remarks in an editorial (Sci Transl Med. 2017;9:eaam6567).
Several different currently approved immunomodulatory therapies ameliorated arthritis symptoms in chikungunya-infected mice in two studies that separate teams of researchers published online Feb. 1 in Science Translational Medicine.
The first team, led by Jonathan J. Miner, MD, PhD, of Washington University in St. Louis tested six different approved oral and biologic antirheumatic agents (along with control agents) in chikungunya virus-infected mice with acute arthritis and foot swelling (Sci Transl Med. 2017;9:eaah3438).
When the researchers paired abatacept with an antiviral therapy (monoclonal anti-CHIKV human antibody) the combination “was highly effective at reducing joint inflammation, periarticular swelling, migration of inflammatory leukocytes, and infection, even when administered several days after virus inoculation,” Dr. Miner and his colleagues wrote.
The researchers concluded that a combination of anti-inflammatory and antibody-based antiviral therapy “may serve as a model for treating humans with arthritis caused by CHIKV or other related viruses.”
In the second study, researchers led by Teck-Hui Teo, PhD, of the Agency for Science, Technology and Research (A*STAR) in Singapore, further elucidated the mechanisms by which CHIKV proteins act on T cells (Sci Transl Med. 2017;9:eaal1333). They also found that CHIKV-infected mice treated with fingolimod (Gilenya), a drug that blocks T-cell migration from the lymph nodes to the joints and is approved for the treatment of multiple sclerosis, saw reduced arthritis symptoms even without reduction of viral replication.
Infection with the chikungunya virus can produce arthritis that mimics symptoms of rheumatoid arthritis and may in some cases lead to joint damage. Though the mechanisms driving chikungunya-related arthritis are not well understood, preliminary studies have suggested a T-cell–mediated adverse response.
The Singapore team received funding from its own agency, A*STAR, while the Washington University researchers received grants from the National Institutes of Health and the Rheumatology Research Foundation. Two coauthors on the U.S. study reported extensive commercial conflicts, including consulting and advisory relationships with pharmaceutical and vaccine manufacturers, and one patent.
Several different currently approved immunomodulatory therapies ameliorated arthritis symptoms in chikungunya-infected mice in two studies that separate teams of researchers published online Feb. 1 in Science Translational Medicine.
The first team, led by Jonathan J. Miner, MD, PhD, of Washington University in St. Louis tested six different approved oral and biologic antirheumatic agents (along with control agents) in chikungunya virus-infected mice with acute arthritis and foot swelling (Sci Transl Med. 2017;9:eaah3438).
When the researchers paired abatacept with an antiviral therapy (monoclonal anti-CHIKV human antibody) the combination “was highly effective at reducing joint inflammation, periarticular swelling, migration of inflammatory leukocytes, and infection, even when administered several days after virus inoculation,” Dr. Miner and his colleagues wrote.
The researchers concluded that a combination of anti-inflammatory and antibody-based antiviral therapy “may serve as a model for treating humans with arthritis caused by CHIKV or other related viruses.”
In the second study, researchers led by Teck-Hui Teo, PhD, of the Agency for Science, Technology and Research (A*STAR) in Singapore, further elucidated the mechanisms by which CHIKV proteins act on T cells (Sci Transl Med. 2017;9:eaal1333). They also found that CHIKV-infected mice treated with fingolimod (Gilenya), a drug that blocks T-cell migration from the lymph nodes to the joints and is approved for the treatment of multiple sclerosis, saw reduced arthritis symptoms even without reduction of viral replication.
Infection with the chikungunya virus can produce arthritis that mimics symptoms of rheumatoid arthritis and may in some cases lead to joint damage. Though the mechanisms driving chikungunya-related arthritis are not well understood, preliminary studies have suggested a T-cell–mediated adverse response.
The Singapore team received funding from its own agency, A*STAR, while the Washington University researchers received grants from the National Institutes of Health and the Rheumatology Research Foundation. Two coauthors on the U.S. study reported extensive commercial conflicts, including consulting and advisory relationships with pharmaceutical and vaccine manufacturers, and one patent.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point:
Major finding: Abatacept, tofacitinib, and fingolimod all reduced arthritis symptoms, compared with controls.
Data source: Two studies testing multiple immunomodulatory or antirheumatic agents in chikungunya virus–infected mice.
Disclosures: The Agency for Science, Technology and Research (A*STAR) funded the Singapore researchers, while grants from the NIH and the Rheumatology Research Foundation funded the U.S. team. Two coauthors on the U.S. study disclosed extensive financial relationships with multiple pharmaceutical and vaccine manufacturers.
West Nile virus accounted for 95% of domestic arboviral disease in 2015
West Nile virus was the most common cause of domestically acquired arboviral disease in the United States in 2015, according to a report from the Centers for Disease Control and Prevention.
A total of 2,282 cases of arboviral disease were reported to the CDC in 2015. Of those, 2,175 cases were caused by the West Nile virus. Of the patients with WNV, 1,616 were hospitalized because of the disease, and 146 died. Neuroinvasive WNV, which occurred in 1,455 cases, accounted for 1,382 of 1,616 WNV hospitalizations and 142 of 146 deaths.
Of the 107 non-WNV arbovirus cases reported to the CDC, 55 were La Crosse virus, 23 were St. Louis encephalitis, 11 were Jamestown Canyon virus, 7 were Powassan virus, and 6 were eastern equine encephalitis. In addition to La Crosse and Jamestown Canyon, 4 cases of additional California serogroup viruses were reported, as was 1 case of Cache Valley virus.
“Health care providers should consider arboviral infections in the differential diagnosis of cases of aseptic meningitis and encephalitis, obtain appropriate specimens for laboratory testing, and promptly report cases to public health authorities. Because human vaccines against domestic arboviruses are not available, prevention depends on community and household efforts to reduce vector populations, personal protective measures to decrease exposure to mosquitoes and ticks, and screening of blood donors,” the CDC investigators concluded.
Find the full report in the MMWR (doi: 10.15585/mmwr.mm6602a3).
West Nile virus was the most common cause of domestically acquired arboviral disease in the United States in 2015, according to a report from the Centers for Disease Control and Prevention.
A total of 2,282 cases of arboviral disease were reported to the CDC in 2015. Of those, 2,175 cases were caused by the West Nile virus. Of the patients with WNV, 1,616 were hospitalized because of the disease, and 146 died. Neuroinvasive WNV, which occurred in 1,455 cases, accounted for 1,382 of 1,616 WNV hospitalizations and 142 of 146 deaths.
Of the 107 non-WNV arbovirus cases reported to the CDC, 55 were La Crosse virus, 23 were St. Louis encephalitis, 11 were Jamestown Canyon virus, 7 were Powassan virus, and 6 were eastern equine encephalitis. In addition to La Crosse and Jamestown Canyon, 4 cases of additional California serogroup viruses were reported, as was 1 case of Cache Valley virus.
“Health care providers should consider arboviral infections in the differential diagnosis of cases of aseptic meningitis and encephalitis, obtain appropriate specimens for laboratory testing, and promptly report cases to public health authorities. Because human vaccines against domestic arboviruses are not available, prevention depends on community and household efforts to reduce vector populations, personal protective measures to decrease exposure to mosquitoes and ticks, and screening of blood donors,” the CDC investigators concluded.
Find the full report in the MMWR (doi: 10.15585/mmwr.mm6602a3).
West Nile virus was the most common cause of domestically acquired arboviral disease in the United States in 2015, according to a report from the Centers for Disease Control and Prevention.
A total of 2,282 cases of arboviral disease were reported to the CDC in 2015. Of those, 2,175 cases were caused by the West Nile virus. Of the patients with WNV, 1,616 were hospitalized because of the disease, and 146 died. Neuroinvasive WNV, which occurred in 1,455 cases, accounted for 1,382 of 1,616 WNV hospitalizations and 142 of 146 deaths.
Of the 107 non-WNV arbovirus cases reported to the CDC, 55 were La Crosse virus, 23 were St. Louis encephalitis, 11 were Jamestown Canyon virus, 7 were Powassan virus, and 6 were eastern equine encephalitis. In addition to La Crosse and Jamestown Canyon, 4 cases of additional California serogroup viruses were reported, as was 1 case of Cache Valley virus.
“Health care providers should consider arboviral infections in the differential diagnosis of cases of aseptic meningitis and encephalitis, obtain appropriate specimens for laboratory testing, and promptly report cases to public health authorities. Because human vaccines against domestic arboviruses are not available, prevention depends on community and household efforts to reduce vector populations, personal protective measures to decrease exposure to mosquitoes and ticks, and screening of blood donors,” the CDC investigators concluded.
Find the full report in the MMWR (doi: 10.15585/mmwr.mm6602a3).
FROM MORBIDITY AND MORTALITY REPORT