by
Trevor Toy;
Gi Deok Pak;
Pham Duc Trung;
James I Campbell;
Muna Ahmed El Tayeb;
Vera Von Kalckreuth;
Justin Im;
Ursula Panzner;
Ligia Maria Cruz Espinoza;
Daniel Eibach;
Denise Myriam Dekker;
Se Eun Park;
Hyon Jin Jeon;
Frank Konings;
Ondari D Mogeni;
Leonard Cosmas;
Morten Bjerregaard-Andersen;
Nagla Gasmelseed;
Julian T Hertz;
Robert F Breiman
Background: Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum β-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa.
Methods: Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for β-lactamase were performed on all pathogens.
Results: Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity.
Conclusions: Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.
Chronic particulate matter less than 2.5 μm in diameter (PM2.5) exposure can leave infants more susceptible to illness. Our objective is to estimate associations of the chronic PM2.5exposure with infant bronchiolitis and otitis media (OM) clinical encounters. We obtained all first time bronchiolitis (n = 18,029) and OM (n = 40,042) clinical encounters among children less than 12 and 36 months of age, respectively, diagnosed from 2001 to 2009 and two controls per case matched on birthdate and gestational age from the Pregnancy to Early Life Longitudinal data linkage system in Massachusetts. We applied conditional logistic regression to estimate odds ratios (OR) and confidence intervals (CI) per 2-μg/m3increase in lifetime average satellite based PM2.5exposure.Effect modification was assessed by age, gestational age, frequency of clinical encounter, and income. We examined associations between residential distance to roadways, traffic density, and infant bronchiolitis and OM risk. PM2.5was not associated with infant bronchiolitis (OR = 1.02, 95% CI = 1.00, 1.04) and inversely associated with OM (OR = 0.97, 95% CI = 0.95, 0.99). There was no evidence of effect modification. Compared to infants living near low traffic density, infants residing in high traffic density had elevated risk of bronchiolitis (OR = 1.23, 95% CI = 1.14, 1.31) but not OM (OR = 0.98, 95% CI = 0.93, 1.02) clinical encounter. We did not find strong evidence to support an association between early-life long-term PM2.5exposure and infant bronchiolitis or OM. Bronchiolitis risk was increased among infants living near high traffic density.
Purpose of Review: People who are incarcerated have a disproportionately high risk of HIV infection. They also tend to have risk factors associated with underutilization of antiretroviral therapy (ART) such as substance abuse, mental illness, and poor access to care. In this review, we describe how incarceration is a marker of vulnerability for suboptimal HIV care, and also how criminal justice settings may be leveraged as a platform for promoting testing, linkage, and retention in HIV care for a high-risk, marginalized population. Recent Findings: In both prisons and jails, routine, opt-out HIV testing strategies are more appropriate for screening correctional populations than traditional, risk-based strategies. Rapid HIV testing is feasible and acceptable in busy, urban jail settings. Although ART is successfully administered in many prison settings, release to the community is strongly associated with inconsistent access to medications and other structural factors leading to loss of viral suppression. Summary: Collaborations among HIV clinicians, criminal justice personnel, and public health practitioners represent an important strategy for turning the tide on the HIV epidemic. Success will depend upon scaled-up efforts to seek individuals with undiagnosed infection and bring those who are out-of-care into long-term treatment.
by
Lesley S. Park;
Janet P. Tate;
Keith Sigel;
David Rimland;
Kristina Crothers;
Cynthia Gibert;
Maria C. Rodriguez-Barradas;
Matthew Bidwell Goetz;
Roger J. Bedimo;
Sheldon T. Brown;
Amy C. Justice;
Robert Dubrow
Objective: Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era.
Design: Prospective cohort study.
Methods: We followed 44 787 HIV+ and 96 852 demographically matched uninfected persons during 1997–2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with incidence rate and IRR period trend P values for cancer groupings and specific cancer types.
Results: We observed 3714 incident cancer diagnoses in HIV+ and 5760 in uninfected persons. The HIV+ all-cancer crude incidence rate increased between 1997–2000 and 2009–2012 (P trend = 0.0019). However, after standardization, we observed highly significant HIV+ incidence rate declines for all cancer (25% decline; P trend <0.0001), AIDS-defining cancers (55% decline; P trend <0.0001), nonAIDS-defining cancers (NADC; 15% decline; P trend = 0.0003), and nonvirus-related NADC (20% decline; P trend <0.0001); significant IRR declines for all cancer (from 2.0 to 1.6; P trend <0.0001), AIDS-defining cancers (from 19 to 5.5; P trend <0.0001), and nonvirus-related NADC (from 1.4 to 1.2; P trend = 0.049); and borderline significant IRR declines for NADC (from 1.6 to 1.4; P trend = 0.078) and virus-related NADC (from 4.9 to 3.5; P trend = 0.071).
Conclusion: Improved HIV care resulting in improved immune function most likely contributed to the HIV+ incidence rate and the IRR declines. Further promotion of early and sustained ART, improved ART regimens, reduction of traditional cancer risk factor (e.g. smoking) prevalence, and evidence-based screening could contribute to future cancer incidence declines among HIV+ persons.
Sex and age differences in food preferences may be reflected in the demographics of outbreaks. Outbreaks from 1998–2015 with a single confirmed implicated food source in the Centers for Disease Control and Prevention Foodborne Disease Outbreak Surveillance System were analysed using logistic regression to assess associations between a food category, sex and age. Males were more likely to be involved in outbreaks attributed to beef, pork, game, dairy and shellfish; females were more likely to be involved in grains-beans, nuts-seeds, fruits, sprouts and vegetable row crops outbreaks. Children <5-years-old were more likely than other age groups to be involved in dairy outbreaks, children 5–19-years-old were most likely to be involved in beef and game outbreaks, adults 20–49-years-old were most likely to be involved in fish, shellfish and sprout outbreaks and adults 50-years-old were most likely to be involved in turkey outbreaks. Age and sex are associated with specific food categories in outbreaks. This information may be useful in helping to identify sources of foodborne disease outbreaks.
Rotavirus vaccines were introduced in the United States in 2006, and in the years since they have fundamentally altered the seasonality of rotavirus infection and have shifted disease outbreaks from annual epidemics to biennial epidemics. We investigated whether season and year of birth have emerged as risk factors for rotavirus or have affected vaccine performance. We constructed a retrospective birth cohort of US children under age 5 years using the 2001-2014 MarketScan database (Truven Health Analytics, Chicago, Illinois).We evaluated the associations of season of birth, even/odd year of birth, and interactions with vaccination.We fitted Cox proportional hazards models to estimate the hazard of rotavirus hospitalization according to calendar year of birth and season of birth assessed for interaction with vaccination. After the introduction of rotavirus vaccine, we observed monotonically decreasing rates of rotavirus hospitalization for each subsequent birth cohort but a biennial incidence pattern by calendar year. In the postvaccine period, children born in odd calendar years had a higher hazard of rotavirus hospitalization than those born in even years. Children born in winter had the highest hazard of hospitalization but also had greater vaccine effectiveness than children born in spring, summer, or fall. With the emergence of a strong biennial pattern of disease following vaccine introduction, the timing of a child's birth has become a risk factor for rotavirus infection.
HIV disproportionately affects black men who have sex with men, and herpes simplex virus type 2 is known to increase acquisition of HIV. However, data on racial disparities in herpes simplex virus type 2 prevalence and risk factors are limited among men who have sex with men in the United States. InvolveMENt was a cohort study of black and white HIV-negative men who have sex with men in Atlanta, GA. Univariate and multivariate cross-sectional associations with herpes simplex virus type 2 seroprevalence were assessed among 455 HIV-negative men who have sex with men for demographic, behavioural and social determinant risk factors using logistic regression. Seroprevalence of herpes simplex virus type 2 was 23% (48/211) for black and 16% (38/244) for white men who have sex with men (p = 0.05). Education, poverty, drug/alcohol use, incarceration, circumcision, unprotected anal intercourse, and condom use were not associated with herpes simplex virus type 2. In multivariate analyses, black race for those ≤25 years, but not >25 years, and number of sexual partners were significantly associated. Young black men who have sex with men are disproportionately affected by herpes simplex virus type 2, which may contribute to disparities in HIV acquisition. An extensive assessment of risk factors did not explain this disparity in herpes simplex virus type 2 infection suggesting differences in susceptibility or partner characteristics.
by
Gamola Z. Fortenberry;
John D. Meeker;
Brisa N. Sanchez;
Dana Boyd Barr;
Parinya Panuwet;
David Bellinger;
Lourdes Schnaas;
Maritsa Solano-Gonzalez;
Adrienne S. Ettinger;
Mauricio Hernandez-Avila;
Howard Hu;
Martha Maria Tellez-Rojo
Attention Deficit Hyperactivity Disorder (ADHD) is the most commonly diagnosed and studied cognitive and behavioral disorder in school-age children. The etiology of ADHD and ADHD-related behavior is unclear, but genetic and environmental factors, such as pesticides, have been hypothesized. The objective of this study was to investigate the relationship between in utero exposure to chlorpyrifos, chlorpyrifos-methyl, and/or 3,5,6-trichloro-2-pyridinol (TCPY) and ADHD in school-age Mexican children using TCPY as a biomarker of exposure. The temporal reliability of repeated maternal urinary TCPY concentrations across trimesters was also explored (N= 21). To explore associations with ADHD-related outcomes in children, third trimester urinary TCPY concentrations in were measured in 187 mother-child pairs from a prospective birth cohort. Child neurodevelopment in children 6-11 years of age was assessed using Conners' Parental Rating Scales-Revised (CRS-R), Conners' Continuous Performance Test (CPT), and Behavior Assessment System for Children-2 (BASC-2). Multivariable linear regression models were used to test relationships for all children combined and also stratified by sex. Intraclass correlation coefficients (ICC) calculations were based on a random effects model. The ICC was 0.41 for uncorrected TCPY, and ranged from 0.29 to 0.32 for specific gravity-corrected TCPY. We did not observe any statistically significant associations between tertiles of maternal TCPY concentrations and ADHD-related outcomes in children. However, compared to the lowest tertile we found suggestive evidence for increased ADHD index in the highest TCPY tertile in boys (β= 5.55 points; 95% CI (-0.19, 11.3); p= 0.06) and increased attention problems for the middle tertile in girls (β= 5.81 points; 95% CI (-0.75, 12.4); p= 0.08). Considering the continued widespread agricultural and possible residential use of chlorpyrifos and chlorpyrifos-methyl in Mexico and the educational implications of cognitive and behavior deficits, these relationships deserve further study.
Purpose of Review: Detailed genetic and structural characterization has revealed that broadly neutralizing antibodies (bnAbs) against HIV-1 have unusually high levels of somatic hypermutation, long CDRH3 domains, and the ability to target one of four sites of vulnerability on the HIV-1 envelope (Env) glycoproteins. A current priority is to understand how bnAbs are generated during natural infection, and translate this information into immunogens that can elicit bnAb following vaccination. RECENT FINDINGS: Strain-specific neutralizing antibodies can acquire broad neutralizing capacity when the transmitted/founder Env or a specific Env variant is recognized by an unmutated rearranged germline that has the capacity to develop bnAb-like features. This event could be relatively infrequent, as only certain germlines appear to possess inherent features needed for bnAb activity. Furthermore, the glycosylation pattern and diversity of circulating HIV-1 Envs, as well as the state of the B-cell compartment, may influence the activation and maturation of certain antibody lineages. SUMMARY: Collectively, studies over the last year have suggested that the development of HIV-1 Env immunogens that bind and activate bnAb-like germlines is feasible. However, more information about the features of Env variants and the host factors that lead to breadth during natural infection are needed to elicit bnAbs through immunization.
by
Debrah I. Boeras;
Nicole Luisi;
Etienne Karita;
Shila McKinney;
Tyronza Sharkey;
Michelle Keeling;
Elwyn Chomba;
Colleen Kraft;
Kristin Wall;
Jean Bizimana;
William Kilembe;
Amanda Tichacek;
Angela M. Caliendo;
Eric Hunter;
Susan Allen
Background: Many HIV voluntary testing and counselling centres in Africa use rapid antibody tests, in parallel or in sequence, to establish same-day HIV status. The interpretation of indeterminate or discrepant results between different rapid tests on one sample poses a challenge. We investigated the use of an algorithm using three serial rapid HIV tests in cohabiting couples to resolve unclear serostatuses. Methods. Heterosexual couples visited the Rwanda Zambia HIV Research Group testing centres in Kigali, Rwanda, and Lusaka, Zambia, to assess HIV infection status. Individuals with unclear HIV rapid antibody test results (indeterminate) or discrepant results were asked to return for repeat testing to resolve HIV status. If either partner of a couple tested positive or indeterminate with the screening test, both partners were tested with a confirmatory test. Individuals with indeterminate or discrepant results were further tested with a tie-breaker and monthly retesting. HIV-RNA viral load was determined when HIV status was not resolved by follow-up rapid testing. Individuals were classified based on two of three initial tests as "Positive", "Negative" or "Other". Follow-up testing and/or HIV-RNA viral load testing determined them as "Infected", "Uninfected" or "Unresolved". Results: Of 45,820 individuals tested as couples, 2.3% (4.1% of couples) had at least one discrepant or indeterminate rapid result. A total of 65% of those individuals had follow-up testing and of those individuals initially classified as "Negative" by three initial rapid tests, less than 1% were resolved as "Infected". In contrast, of those individuals with at least one discrepant or indeterminate result who were initially classified as "Positive", only 46% were resolved as "Infected", while the remainder was resolved as "Uninfected" (46%) or "Unresolved" (8%). A positive HIV serostatus of one of the partners was a strong predictor of infection in the other partner as 48% of individuals who resolved as "Infected" had an HIV-infected spouse. Conclusions: In more than 45,000 individuals counselled and tested as couples, only 5% of individuals with indeterminate or discrepant rapid HIV test results were HIV infected. This represented only 0.1% of all individuals tested. Thus, algorithms using screening, confirmatory and tie-breaker rapid tests are reliable with two of three tests negative, but not when two of three tests are positive. False positive antibody tests may persist. HIV-positive partner serostatus should prompt repeat testing.