Publications by authors named "Aaron Richterman"

25 Publications

  • Page 1 of 1

Predictors of COVID-19 Seropositivity Among Healthcare Workers: An Important Piece of an Incomplete Puzzle.

J Hosp Med 2021 May;16(5):320

Division of Infectious Diseases, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.12788/jhm.3632DOI Listing
May 2021

A defense of the classical model of transmission of respiratory pathogens.

Clin Infect Dis 2021 Jan 12. Epub 2021 Jan 12.

Division of Infectious Diseases, Hospital of the University of Pennsylvania, Philadelphia, New York.

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http://dx.doi.org/10.1093/cid/ciab016DOI Listing
January 2021

Towards an accurate and systematic characterisation of persistently asymptomatic infection with SARS-CoV-2.

Lancet Infect Dis 2021 06 7;21(6):e163-e169. Epub 2020 Dec 7.

Division of Infection and Global Health Research, School of Medicine, University of St Andrews, St Andrews, UK.

People with persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience no symptoms throughout the course of infection, and pre-symptomatic individuals become infectious days before they report symptoms. Transmission of SARS-CoV-2 from individuals without symptoms contributes to pandemic spread, but the extent of transmission from persistently asymptomatic individuals remains unknown. We describe three methodological issues that hinder attempts to estimate this proportion. First, incomplete symptom assessment probably overestimates the asymptomatic fraction. Second, studies with inadequate follow-up misclassify pre-symptomatic individuals. Third, serological studies might identify people with previously unrecognised infection, but reliance on poorly defined antibody responses and retrospective symptom assessment might result in misclassification. We provide recommendations regarding definitions, detection, documentation, and follow-up to improve the identification and evaluation of people with persistently asymptomatic SARS-CoV-2 infection and their contacts. Accurate characterisation of the persistently asymptomatic fraction of infected individuals might shed light on COVID-19 pathogenesis and transmission dynamics, and inform public health responses.
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http://dx.doi.org/10.1016/S1473-3099(20)30837-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834404PMC
June 2021

Hospital-Acquired SARS-CoV-2 Infection: Lessons for Public Health.

JAMA 2020 Dec;324(21):2155-2156

Division of Infection and Global Health Research, School of Medicine, University of St Andrews, Fife, Scotland, United Kingdom.

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http://dx.doi.org/10.1001/jama.2020.21399DOI Listing
December 2020

New Perspectives on Antimicrobial Agents: Remdesivir Treatment for COVID-19.

Antimicrob Agents Chemother 2020 12 16;65(1). Epub 2020 Dec 16.

Division of Infectious Diseases, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is the prodrug of an adenosine analogue that inhibits viral replication of several RNA virus families, including Preclinical data in animal models of coronavirus diseases, including COVID-19, have demonstrated that early treatment with remdesivir leads to improved survival, decreased lung injury, and decreased levels of viral RNA. Recent clinical data have demonstrated the clinical activity of remdesivir in terms of faster time to recovery in patients with severe COVID-19 and higher odds of improved clinical status in patients with moderate COVID-19. Here, clinical trials published to date are presented and appraised. Remdesivir's potential benefits and its favorable adverse-event profile make it an option for the treatment of COVID-19. This article examines the available literature describing remdesivir's pharmacology, pharmacokinetics, and preclinical and clinical data.
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http://dx.doi.org/10.1128/AAC.01814-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927874PMC
December 2020

Omadacycline for the Treatment of Disease: A Case Series.

Open Forum Infect Dis 2020 Oct 9;7(10):ofaa415. Epub 2020 Sep 9.

Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Omadacycline is an aminomethylcycline antimicrobial approved by the US Food and Drug Administration in 2018 for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It has in vitro activity against nontuberculous mycobacteria, including complex, but clinical data for this indication are lacking.

Methods: Omadacycline use was reviewed at an 804-bed academic medical center. Patients were included if they received omadacycline for culture-proven disease in 2019.

Results: Four patients received omadacycline for the treatment of culture-positive disease in 2019. Two patients had cutaneous disease, 1 had pulmonary disease, and 1 had osteomyelitis and bacteremia. The patients received omadacycline for a median duration of 166 days (range, 104-227) along with a combination of other antimicrobial agents. Omadacycline-containing regimens were associated with a clinical cure in 3 of 4 patients, with 1 patient improving on ongoing treatment. Omadacycline's tolerability was acceptable for patients with disease, with 1 patient discontinuing therapy in month 6 due to nausea.

Conclusions: Omadacycline is a novel oral option for the treatment of disease, for which safe and effective options are needed. Although this case series is promising, further data are required to determine omadacycline's definitive role in the treatment of disease.
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http://dx.doi.org/10.1093/ofid/ofaa415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566545PMC
October 2020

Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors.

Ann Intern Med 2021 01 17;174(1):69-79. Epub 2020 Sep 17.

Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts (P.E.S.).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented. The virus has heterogeneous transmission dynamics: Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called "superspreading events." Evidence-based policies and practices should incorporate the accumulating knowledge about transmission of SARS-CoV-2 to help educate the public and slow the spread of this virus.
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http://dx.doi.org/10.7326/M20-5008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505025PMC
January 2021

Mortality Over Long-term Follow-up for People With HIV Receiving Longitudinal Care and Antiretroviral Therapy in Rural Haiti.

Open Forum Infect Dis 2020 Aug 11;7(8):ofaa328. Epub 2020 Aug 11.

Center for Global Health, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Deaths from HIV have fallen dramatically with the increasing availability of fully suppressive antiretroviral therapy (ART), and yet HIV remains the ninth leading cause of death in low-income countries. As more people with HIV enter care and receive ART, the focus will need to shift from expanding ART to including long-term program effectiveness and outcomes for people with HIV already engaged in care.

Methods: We evaluated risk factors for mortality among people with HIV on ART receiving longitudinal care in rural Haiti. We assessed baseline characteristics using a household survey and abstracted clinical characteristics from the electronic record. We used multivariable Cox regression models to identify risk factors for mortality.

Results: There were 464 people included in this study with a median follow-up (interquartile range [IQR]) of 69 (44-77) months, during which time 37 (8%) were lost to follow-up and 118 (25%) died (median time to death [IQR], 29 [12-53] months). After adjustment, poverty (adjusted hazard ratio [AHR], 1.12 per 10-percentage point increased probability; 95% CI, 1.01-1.24) and single marital status (AHR, 1.59; 95% CI, 1.08-2.36) were associated with increased mortality. Age (AHR, 0.78 per 10-year increase; 95% CI, 0.64-0.94), role function quality of life (AHR, 0.75 per quintile increase; 95% CI, 0.62-0.90), and CD4 count (AHR, 0.66 per 100 cells/μL; 95% CI, 0.58-0.75) were associated with decreased mortality.

Conclusions: Poverty, marital status, and quality of life were associated with mortality. Social protection should be evaluated as a strategy to reduce mortality for people with HIV in concert with increasing access to ART.
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http://dx.doi.org/10.1093/ofid/ofaa328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442269PMC
August 2020

Barriers and facilitators influencing facility-based childbirth in rural Haiti: a mixed method study with a convergent design.

BMJ Glob Health 2020 08;5(8)

Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.

Introduction: Haiti has the highest maternal mortality rate in the Western Hemisphere. Facility-based childbirth is promoted as the standard of care for reducing maternal and neonatal mortality. We conducted a convergent, mixed methods study to assess barriers and facilitators to facility-based childbirth at Hôpital Universitaire de Mirebalais (HUM) in Mirebalais, Haiti.

Methods: We conducted secondary analyses of a prospective cohort of pregnant women seeking antenatal care at HUM and quantitatively assessed predictors of not having a facility-based childbirth at HUM. We prospectively enrolled 30 pregnant women and interviewed them about their experiences delivering at home or at HUM.

Results: Of 1105 pregnant women seeking antenatal care at the hospital between May and December 2017, 773 (70%) returned to the hospital for facility-based childbirth. In multivariable analyses, living farther from the hospital (adjusted OR (AOR)=0.73; 95% CI 0.56 to 0.96), poverty (AOR=0.93; 95% CI 0.88 to 0.99) and household hunger (AOR=0.45; 95% CI 0.26 to 0.79) were associated with not having a facility-based childbirth. Primigravid women were more likely to have a facility-based childbirth (AOR=1.34, 95% CI 1.02 to 1.76). Qualitative data provided insight into the value women place on traditional birth attendants ('matrons') during home-based childbirths. While women perceived facility-based childbirths as better equipped to handle birth complications, barriers such as distance, costs of transportation and supplies, discomfort of facility birthing practices and mistreatment by medical staff resulted in negative perceptions of facility-based childbirths.

Conclusion: Pregnant women in rural Haiti must overcome substantial structural barriers and forfeit valued support from traditional birth attendants when they pursue facility-based childbirths. If traditional birth attendants could be involved in care alongside midwives at facilities, women may be more inclined to deliver there. While complex structural barriers remain, the inclusion of matrons at facilities may increase uptake of facility-based childbirths, and ultimately improve maternal and neonatal outcomes.
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http://dx.doi.org/10.1136/bmjgh-2020-002526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445336PMC
August 2020

Food insecurity as a risk factor for preterm birth: a prospective facility-based cohort study in rural Haiti.

BMJ Glob Health 2020 07;5(7)

Center for Global Health, Massachusetts General Hospital, Boston, Massachusetts, USA.

Introduction: Haiti has an estimated neonatal mortality rate of 32/1000 live births, the highest in the Western Hemisphere. Preterm birth and being born small for gestational age (SGA) are major causes of adverse neonatal outcomes worldwide. To reduce preterm birth and infants born SGA, it is important to understand which women are most at risk and how risk varies within countries. There are few studies estimating the prevalence and risk factors for these conditions in Haiti, particularly in rural regions.

Methods: We conducted a prospective cohort study of pregnant women at a rural tertiary care centre in Haiti from May to December 2017. We collected data during interviews and from the medical record. We built multivariable models to identify risk factors for preterm birth and being born SGA among women who had a facility-based delivery.

Results: 1089 pregnant women delivered at the hospital and were included in this analysis. Median gestational age at delivery was 38 weeks (IQR 36-40). In multivariable analyses, risk factors for preterm birth included maternal age <20 years (adjusted OR (AOR) 1.76, 95% CI 1.14 to 2.72) and >34 years (AOR 1.46, 95% CI 1.01 to 2.11) and severe hunger in the household (AOR 1.57, 95% CI 1.09 to 2.26). Risk factors for SGA were age >34 years (AOR 1.76, 95% CI 1.18 to 2.59), twin pregnancy (AOR 3.28, 95% CI 1.20 to 8.95) and first pregnancy (AOR 1.57, 95% CI 1.12 to 2.23). Number of prior abortions was associated with reduced risk for SGA (AOR 0.41, 95% CI 0.17 to 0.97).

Conclusions: Food insecurity as a risk factor for preterm birth stands out as an important addition to the understanding of the risk of neonatal morbidity and mortality. This association highlights a potentially important intervention target to improve birth outcomes and suggests that food support has an important role to play for pregnant women who are food insecure in low-income settings.
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http://dx.doi.org/10.1136/bmjgh-2020-002341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332182PMC
July 2020

Misguided Changes to SNAP - Defending a Public Health Intervention for the Poor.

N Engl J Med 2020 Mar 4;382(13):1191-1193. Epub 2020 Mar 4.

From the Division of Infectious Diseases, Brigham and Women's Hospital (A.R.), the Center for Global Health, Massachusetts General Hospital (A.R., L.C.I.), and the Department of Global Health and Social Medicine, Harvard Medical School (L.C.I.) - all in Boston.

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http://dx.doi.org/10.1056/NEJMp2000253DOI Listing
March 2020

Antiretroviral therapy in older people with HIV.

Curr Opin HIV AIDS 2020 03;15(2):118-125

Division of Infectious Diseases, Brigham and Women's Hospital.

Purpose Of Review: The age of people with HIV) continues to rise, and yet older people have tended to be under-represented or excluded from premarketing studies of antiretroviral therapy (ART). In this review, we highlight special considerations for the use of ART in older people with HIV, with a focus on toxicities associated with specific antiretroviral agents or drug classes as well as key research questions moving forward.

Recent Findings: Like all people with HIV, older people with HIV should be started on ART as soon as possible, regardless of CD4 count, and with a regimen that includes an integrase strand transfer inhibitor (INSTI) and two nucleoside reverse transcriptase inhibitors. Important toxicities to consider when choosing an ART regimen include bone and renal effects related to tenofovir, weight gain related to INSTIs and tenofovir alafenamide, neurocognitive and neuropsychiatric toxicities related to efavirenz, and increased cardiovascular risk associated with abacavir and boosted protease inhibitors. With the ongoing importance of INSTIs as a component of preferred ART regimens, further characterization of INSTI-related weight gain is a critical current research priority in understanding ART toxicity.

Summary: There are multiple potential toxicities of ART to consider when selecting a regimen for older people. Specific agents or drug classes have been implicated in adverse bone or renal effects, weight gain, neuropsychiatric and neurocognitive effects, and cardiovascular risk.
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http://dx.doi.org/10.1097/COH.0000000000000614DOI Listing
March 2020

Identification of Racial Inequities in Access to Specialized Inpatient Heart Failure Care at an Academic Medical Center.

Circ Heart Fail 2019 11 29;12(11):e006214. Epub 2019 Oct 29.

Division of Cardiovascular Medicine, and Department of Medicine (E.F..L.), Brigham and Women's Hospital, Boston, MA.

Background: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race. This study examined the relationship between race and admission service, and its effect on 30-day readmission and mortality Methods: We performed a retrospective cohort study from September 2008 to November 2017 at a single large urban academic referral center of all patients self-referred to the emergency department and admitted to either the cardiology or general medicine service with a principal diagnosis of HF, who self-identified as white, black, or Latinx. We used multivariable generalized estimating equation models to assess the relationship between race and admission to the cardiology service. We used Cox regression to assess the association between race, admission service, and 30-day readmission and mortality.

Results: Among 1967 unique patients (66.7% white, 23.6% black, and 9.7% Latinx), black and Latinx patients had lower rates of admission to the cardiology service than white patients (adjusted rate ratio, 0.91; 95% CI, 0.84-0.98, for black; adjusted rate ratio, 0.83; 95% CI, 0.72-0.97 for Latinx). Female sex and age >75 years were also independently associated with lower rates of admission to the cardiology service. Admission to the cardiology service was independently associated with decreased readmission within 30 days, independent of race.

Conclusions: Black and Latinx patients were less likely to be admitted to cardiology for HF care. This inequity may, in part, drive racial inequities in HF outcomes.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183732PMC
November 2019

The inverse relationship between national food security and annual cholera incidence: a 30-country analysis.

BMJ Glob Health 2019 18;4(5):e001755. Epub 2019 Sep 18.

Center for Global Health, Massachusetts General Hospital, Boston, Massachusetts, USA.

Introduction: Individual and household-level evidence suggests a relationship between food insecurity and cholera risk. The relationship between national food security and the size of cholera outbreaks is unknown.

Methods: We analysed the relationship between national food security and annual cholera incidence rate from 2012 to 2015 across 30 countries. We used components of the Global Food Security Index (GFSI) as measures of food security. We included countries with available GFSI reporting cases of cholera during the study period, excluding high-income countries. We developed multivariable zero-inflated negative binomial models with annual cholera incidence rate as the outcome, GFSI components as the exposure of interest, fixed effects for country and year, and time-varying effects related to water, sanitation, and hygiene, oral cholera vaccine deployment, healthcare expenditure, conflict and extreme weather.

Results: The 30 countries reported 550 106 total cases of cholera from 2012 to 2015, with a median annual incidence rate of 3.1 cases per 100 000 people (IQR 0.3-9.9). We found independent inverse relationships between cholera and Overall GFSI (incidence rate ratio (IRR) 0.57, 95% CI 0.43 to 0.78), GFSI-Availability (IRR 0.81, 95% CI 0.70 to 0.95) and GFSI-Affordability (IRR 0.76, 95% CI 0.62 to 0.92).

Conclusions: We identified a strong inverse relationship between national food security and annual incidence rate of cholera. In the context of prior evidence at the individual and household levels, this suggests that there is a linkage between food insecurity and cholera at the national level that should be further considered in assessing cholera risk in vulnerable regions and in designing cholera control interventions.
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http://dx.doi.org/10.1136/bmjgh-2019-001755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768341PMC
September 2019

Food insecurity and self-reported cholera in Haitian households: An analysis of the 2012 Demographic and Health Survey.

PLoS Negl Trop Dis 2019 01 30;13(1):e0007134. Epub 2019 Jan 30.

Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.

Background: Both cholera and food insecurity tend to occur in impoverished communities where poor access to food, inadequate sanitation, and an unsafe water supply often coexist. The relationship between the two, however, has not been well-characterized.

Methods: We performed a secondary analysis of household-level data from the 2012 Demographic and Health Survey in Haiti, a nationally and sub-nationally representative cross-sectional household survey conducted every five years. We used multivariable logistic regression to evaluate the relationship between household food security (as measured by the Household Hunger Scale) and (1) reported history of cholera since 2010 by any person in the household and (2) reported death by any person in the household from cholera (among households reporting at least one case). We performed a complete case analysis because there were <1% missing data for all variables.

Results: There were 13,181 households in the survey, 2,104 of which reported at least one household member with history of cholera. After adjustment for potential confounders, both moderate hunger in the household [Adjusted Odds Ratio (AOR) 1.51, 95% Confidence Interval (CI) 1.30-1.76; p <.0001] and severe hunger in the household (AOR 1.73, 95% CI 1.45-2.08; p <.0001) were significantly associated with reported history of cholera in the household. Severe hunger in the household (AOR 1.85, 95% CI 1.05-3.26; p = 0.03), but not moderate hunger in the household, was independently associated with reported death from cholera in households with at least one case of cholera.

Conclusions: In this study we identified an independent relationship between household food insecurity and both reported history of cholera and death from cholera in a general population. The directionality of this relationship is uncertain and should be further explored in future prospective research.
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http://dx.doi.org/10.1371/journal.pntd.0007134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370226PMC
January 2019

Individual and Household Risk Factors for Symptomatic Cholera Infection: A Systematic Review and Meta-analysis.

J Infect Dis 2018 10;218(suppl_3):S154-S164

Center for Global Health, Massachusetts General Hospital.

Background: Cholera has caused 7 global pandemics, including the current one which has been ongoing since 1961. A systematic review of risk factors for symptomatic cholera infection has not been previously published.

Methods: In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we performed a systematic review and meta-analysis of individual and household risk factors for symptomatic cholera infection.

Results: We identified 110 studies eligible for inclusion in qualitative synthesis. Factors associated with symptomatic cholera that were eligible for meta-analysis included education less than secondary level (summary odds ratio [SOR], 2.64; 95% confidence interval [CI], 1.41-4.92; I2 = 8%), unimproved water source (SOR, 3.48; 95% CI, 2.18-5.54; I2 = 77%), open container water storage (SOR, 2.03; 95% CI, 1.09-3.76; I2 = 62%), consumption of food outside the home (SOR, 2.76; 95% CI, 1.62-4.69; I2 = 64%), household contact with cholera (SOR, 2.91; 95% CI, 1.62-5.25; I2 = 89%), water treatment (SOR, 0.37; 95% CI, .21-.63; I2 = 74%), and handwashing (SOR, 0.29; 95% CI, .20-.43; I2 = 37%). Other notable associations with symptomatic infection included income/wealth, blood group, gastric acidity, infant breastfeeding status, and human immunodeficiency virus infection.

Conclusions: We identified potential risk factors for symptomatic cholera infection including environmental characteristics, socioeconomic factors, and intrinsic patient factors. Ultimately, a combination of interventional approaches targeting various groups with risk-adapted intensities may prove to be the optimal strategy for cholera control.
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http://dx.doi.org/10.1093/infdis/jiy444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188541PMC
October 2018

Cash interventions to improve clinical outcomes for pulmonary tuberculosis: systematic review and meta-analysis.

Bull World Health Organ 2018 Jul 4;96(7):471-483. Epub 2018 Jun 4.

Center for Global Health, Massachusetts General Hospital, Boston, USA.

Objective: To assess cash transfer interventions for improving treatment outcomes of active pulmonary tuberculosis in low- and middle-income countries.

Methods: We searched PubMed®, Embase®, Cochrane Library and ClinicalTrials.gov for studies published until 4 August 2017 that reported on cash transfer interventions during the treatment of active pulmonary tuberculosis in low- and middle-income countries. Our primary outcome was a positive clinical outcome, defined as treatment success, treatment completion or microbiologic cure. Using the purchasing power parity conversion factor, we converted the amount of cash received per patient within each study into international dollars (Int$). We calculated odds ratio (OR) for the primary outcome using a random effects meta-analysis.

Findings: Eight studies met eligibility criteria for review inclusion. Seven studies assessed a tuberculosis-specific intervention, with average amount of cash ranging from Int$ 193-858. One study assessed a tuberculosis-sensitive intervention, with average amount of Int$ 101. Four studies included non-cash co-interventions. All studies showed better primary outcome for the intervention group than the control group. After excluding three studies with high risk of bias, patients receiving tuberculosis-specific cash transfer were more likely to have a positive clinical outcome than patients in the control groups (OR: 1.77; 95% confidence interval: 1.57-2.01).

Conclusion: The evidence available suggests that patients in low- and middle-income countries receiving cash during treatment for active pulmonary tuberculosis are more likely to have a positive clinical outcome. These findings support the incorporation of cash transfer interventions into social protection schemes within tuberculosis treatment programmes.
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http://dx.doi.org/10.2471/BLT.18.208959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022611PMC
July 2018

Risk Factors for Self-Reported Cholera Within HIV-Affected Households in Rural Haiti.

Open Forum Infect Dis 2018 Jun 31;5(6):ofy127. Epub 2018 May 31.

Center for Global Health, Massachusetts General Hospital, Boston, Massachusetts.

Background: Cholera continues to be a major cause of morbidity and mortality worldwide and is now endemic in Haiti since first being introduced in 2010. Cholera and HIV have significant geographic overlap globally, but little is known about the clinical features and risk of cholera among HIV-infected people and their households.

Methods: We assessed HIV-affected households originally recruited for a randomized controlled trial of food supplements. We assessed for correlation between household and individual factors and reported history of cholera since 2010 using univariable and multivariable analyses.

Results: There were 352 HIV-infected household members, 32 with reported history of medically attended cholera, and 1968 other household members, 55 with reported history of medically attended cholera. Among HIV-infected individuals in this study, no variables correlated with reported history of cholera in univariable analyses. Among all household members, known HIV infection (adjusted odds ratio [AOR], 3.75; 95% CI, 2.43-5.79; < .0001), source of income in the household (AOR, 1.82; 95% CI, 1.05-3.15; = .034), time required to fetch water (AOR, 1.07 per 5-minute increase; 95% CI, 1.01-1.12; = .015), and severe household food insecurity (AOR, 3.23; 95% CI, 1.25-8.34; = .016) were correlated with reported history of cholera in a multivariable analysis.

Conclusions: Known HIV infection, source of household income, time required to fetch water, and severe household food insecurity were independently associated with reported history of medically attended cholera in HIV-affected households in rural Haiti. Further research is required to better understand the interactions between HIV and cholera.
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http://dx.doi.org/10.1093/ofid/ofy127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007289PMC
June 2018

Smear Campaign: Misattribution of Pancytopenia to a Tick-Borne Illness.

J Gen Intern Med 2018 04 22;33(4):570-572. Epub 2017 Dec 22.

Harvard Medical School, Boston, MA, USA.

We report the case of a 51-year-old woman presenting with a targetoid rash and pancytopenia after a tick bite. Initial evaluation was notable for severe neutropenia on the complete blood cell count differential, a positive Lyme IgM antibody, and a peripheral blood smear demonstrating atypical lymphocytes. While her pancytopenia was initially attributed to tick-borne illness, peripheral flow cytometry showed 7% myeloblasts, and a bone marrow biopsy confirmed 60% blasts. The patient was ultimately diagnosed with acute myelogenous leukemia, in addition to early, localized Lyme disease. This case highlights the differential diagnosis for pancytopenia, cytopenia patterns for different tick-borne illnesses, the risk of premature closure in internal medicine, and management of Lyme disease in hosts with altered immunity.
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http://dx.doi.org/10.1007/s11606-017-4241-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880759PMC
April 2018

The Challenges and Promise of HIV-Infected Donors for Solid Organ Transplantation.

Curr Infect Dis Rep 2015 Apr;17(4):471

Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.

Solid organ transplantation is now the standard of care for many HIV-infected patients with end-stage kidney or liver disease. There is an overall organ shortage that affects all transplant candidates, including those with HIV. The use of HIV-infected donors could help alleviate this shortage. The precedent for this approach was set in South Africa, where promising short-term outcomes have been reported in a limited number of HIV-infected recipients of kidney transplants from HIV-infected donors. As a consequence, the HIV Organ Policy Equity (HOPE) Act was passed in the United States, legalizing research into HIV-infected organ donation. In this review, we discuss some of the key issues related to HIV-infected organ donation, including the need for transplant in HIV-infected populations, characterization of the potential donor pool in the USA, criteria for donor selection, concerns specific to the HIV-infected donor, the ethics of HIV-infected organ donation, and the next steps toward making HIV-infected donation a reality in the USA.
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http://dx.doi.org/10.1007/s11908-015-0471-zDOI Listing
April 2015

Graves' disease as immune reconstitution disease in HIV-positive patients is associated with naive and primary thymic emigrant CD4(+) T-cell recovery.

AIDS 2014 Jan;28(1):31-9

aNational Institute of Allergy and Infectious Diseases (NIAID) bBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda cScience Applications International Corporation-Frederick, Frederick National Laboratory, Frederick dClinical Dental Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.

Objective: Immune restoration disease (IRD) can develop in HIV-infected patients following antiretroviral therapy (ART) initiation as unmasking or paradoxical worsening of opportunistic infections and, rarely, autoimmune phenomena. Although IRD usually occurs in the first months of ART during memory CD4 T-cell recovery, Graves' disease occurs as a distinctive late-onset IRD and its pathogenesis is unclear.

Design: Seven patients who developed Graves' disease following ART initiation from the primary HIV care clinic at the National Institutes of Health were retrospectively identified and each was matched with two HIV-infected controls based on age, sex, and baseline CD4 T-cell count. Laboratory evaluations on stored cryopreserved samples were performed.

Methods: Immunophenotyping of peripheral blood mononuclear cells (PBMCs), T-cell receptor excision circle (TREC) analysis in PBMCs, measurement of serum cytokines, and luciferase immunoprecipitation systems (LIPS) analysis for autoimmune antibodies were performed on stored samples for cases and controls at baseline and longitudinally following ART initiation. TSH/thyrotropin receptor (TSH-R) antibody testing was performed on serum from cases. Data were analyzed using nonparametric testing.

Results: In comparison with controls, the proportion of naive CD4 T cells increased significantly (P = 0.0027) in the Graves' disease-IRD patients. TREC/10 PBMCs also increased significantly following ART in Graves' disease-IRD patients compared with controls (P = 0.0071). Similarly, LIPS analysis demonstrated increases in nonthyroid-related autoantibody titers over time following ART in cases compared with controls.

Conclusion: Our data suggest that Graves' disease-IRD, in contrast to early-onset IRD, is associated with naive and primary thymic emigrant CD4 T-cell recovery and inappropriate autoantibody production.
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http://dx.doi.org/10.1097/QAD.0000000000000006DOI Listing
January 2014

Elevated interleukin 8 and T-helper 1 and T-helper 17 cytokine levels prior to antiretroviral therapy in participants who developed immune reconstitution inflammatory syndrome during ACTG A5164.

J Infect Dis 2012 Dec 21;206(11):1715-23. Epub 2012 Sep 21.

Division of Infectious Diseases, Stanford University, Stanford, California 94305–5107, USA.

Background: Immune reconstitution inflammatory syndrome (IRIS) reflects an aberrant immune response that can develop in human immunodeficiency virus-infected patients initiating antiretroviral therapy (ART). Its pathogenesis remains unclear.

Methods: We performed a nested case-control study using specimens from ACTG A5164. We compared plasma biomarkers and T-cell subsets in 19 IRIS and 39 control participants at study entry, ART initiation, and IRIS and used conditional logistic regression to develop IRIS predictive models. We evaluated the effect of corticosteroids on biomarker levels.

Results: Eleven and 8 participants developed paradoxical and unmasking IRIS, respectively, none while still receiving corticosteroids. Compared to controls, cases displayed elevations at study entry in interleukin (IL) 8, T-helper (Th) 1 (IL-2, interferon [IFN]-γ, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN-γ and TNF were strong predictors of IRIS. Participants who received corticosteroids and later developed IRIS had marked increases in IL-6, IL-8, and IFN-γ at the time of IRIS. T-cell activation markers did not differ in cases and controls prior to ART but were increased in cases at the time of IRIS.

Conclusions: Increased IL-8, Th1, and Th17 cytokine levels in IRIS patients precede ART initiation and could help identify patient populations at higher risk for IRIS.
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http://dx.doi.org/10.1093/infdis/jis604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488199PMC
December 2012

Traditional risk factors and D-dimer predict incident cardiovascular disease events in chronic HIV infection.

AIDS 2010 Jun;24(10):1509-17

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Objective: Cardiovascular disease (CVD) contributes significantly to HIV-related morbidity and mortality. Chronic immune activation and inflammation are thought to augment the progression of atherosclerotic disease. In this retrospective, case-control study of HIV-infected individuals, we investigated the association of traditional cardiac risk factors, HIV-related disease, and inflammation with CVD events.

Methods: HIV-infected individuals who experienced an incident CVD event while enrolled in National Institutes of Health clinical protocols from 1995 to 2009 were matched 2: 1 to HIV-infected individuals without known CVD. Markers of inflammation and cell activation were measured in serum or plasma using ELISA-based assays and peripheral mononuclear cells by four-color flow cytometry.

Results: Fifty-two patients experienced an incident CVD event. Events were related to smoking, dyslipidemia, hyperglycemia, and family history as well as elevated D-dimer, soluble vascular cell adhesion molecule-1, tissue inhibitor of metalloproteinase-1, and soluble tissue factor, but not high-sensitivity C-reactive protein. No significant differences in antiviral therapy, CD4 T-cell count, or CD38 and human leukocyte antigen-DR expression were identified between patients and controls. In multivariable analysis, smoking, family history, D-dimer, and glucose were independently related to CVD risk.

Conclusion: In this cohort, CVD risk was related to traditional CVD risk factors and markers of thrombosis and endothelial damage, but not to high-sensitivity C-reactive protein or markers of T-cell activation such as CD38/human leukocyte antigen-DR coexpression. D-dimer may help identify HIV-infected patients at elevated CVD risk.
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http://dx.doi.org/10.1097/QAD.0b013e32833ad914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884071PMC
June 2010