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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.
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.
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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.
The autoinducer-3 (AI-3)/epinephrine (Epi)/norepinephrine (NE) interkingdom signaling system mediates chemical communication between bacteria and their mammalian hosts. The three signals are sensed by the QseC histidine kinase (HK) sensor. Salmonella enterica serovar Typhimurium is a pathogen that uses HKs to sense its environment and regulate virulence. Salmonella serovar Typhimurium invades epithelial cells and survives within macrophages. Invasion of epithelial cells is mediated by the type III secretion system (T3SS) encoded in Salmonella pathogenicity island 1 (SPI-1), while macrophage survival and systemic disease are mediated by the T3SS encoded in SPI-2. Here we show that QseC plays an important role in Salmonella serovar Typhimurium pathogenicity. A qseC mutant was impaired in flagellar motility, in invasion of epithelial cells, and in survival within macrophages and was attenuated for systemic infection in 129x1/SvJ mice. QseC acts globally, regulating expression of genes within SPI-1 and SPI-2 in vitro and in vivo (during infection of mice). Additionally, dopamine β-hydroxylase knockout (Dbh -/- ) mice that do not produce Epi or NE showed different susceptibility to Salmonella serovar Typhimurium infection than wild-type mice. These data suggest that the AI-3/Epi/NE signaling system is a key factor during Salmonella serovar Typhimurium pathogenesis in vitro and in vivo. Elucidation of the role of this interkingdom signaling system in Salmonella serovar Typhimurium should contribute to a better understanding of the complex interplay between the pathogen and the host during infection.
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James E. Voss;
Matthew S. Macauley;
Kenneth A. Rogers;
Francois Villinger;
Lijie Duan;
Liang Shang;
Elizabeth A. Fink;
Raiees Andrabi;
Arnaud D. Colantonio;
James E. Robinson;
Robert Johnson;
Dennis R. Burton;
Ashley T. Haase
Vaccination with SIV mac239 δnef provides robust protection against subsequent challenge with wild-type simian immunodeficiency virus (SIV), but safety issues have precluded designing an HIV-1 vaccine based on a live-attenuated virus concept. Safe immunogens and adjuvants that could reproduce identified immune correlates of SIV mac239 δnef protection therefore offer an alternative path for development of an HIV vaccine. Here we describe SIV envelope trimeric gp41 (gp41t) immunogens based on a protective correlate of antibodies to gp41t concentrated on the path of virus entry by the neonatal Fc receptor (FcRn) in cervical vaginal epithelium. We developed a gp41t immunogen-monophosphoryl lipid A adjuvant liposomal nanoparticle for intramuscular (i.m.) immunization and a gp41t-Fc immunogen for intranasal immunization for pilot studies in mice, rabbits, and rhesus macaques. Repeated immunizations to mimic persistent antigen exposure in infection elicited gp41t antibodies in rhesus macaques that were detectable in FcRn cervical vaginal epithelium, thus recapitulating one key feature of SIV mac239 δnef vaccinated and protected animals. Although this strategy did not reproduce the system of local production of antibody in SIV mac239 δnef-vaccinated animals, passive immunization experiments supported the concept that sufficiently high levels of antibody can be concentrated by the FcRn at mucosal frontlines, thus setting the stage for assessing protection against vaginal challenge by gp41t immunization.
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Samantha I Pitts;
Nisa M Maruthur;
Gayle E Langley;
Tracy Pondo;
Kathleen A Shutt;
Rosemary Hollick;
Stephanie J Schrag;
Ann Thomas;
Megin Nichols;
Monica Farley;
James P Watt;
Lisa Miller;
William Schaffner;
Corinne Holtzman;
Lee H Harrison
Background. Rates of invasive group B Streptococcus (GBS) disease, obesity, and diabetes have increased in US adults. We hypothesized that obesity would be independently associated with an increased risk of invasive GBS disease. Methods. We identified adults with invasive GBS disease within Active Bacterial Core surveillance during 2010-2012 and used population estimates from the Behavioral Risk Factor Surveillance System to calculate invasive GBS incidence rates. We estimated relative risks (RRs) of invasive GBS using Poisson analysis with offset denominators, with obesity categorized as class I/II (body mass index [BMI] = 30-39.9 kg/m2) and class III (BMI ≥ 40.0 kg/m2). Results. In multivariable analysis of 4281 cases, the adjusted RRs of invasive GBS disease were increased for obesity (class I/ II: RR, 1.52; 95% confidence interval [CI], 1.14-2.02; and class III: RR, 4.87; 95% CI, 3.50-6.77; reference overweight) and diabetes (RR, 6.04; 95% CI, 4.77-7.65). The adjusted RR associated with class III obesity was 3-fold among persons with diabetes (95% CI, 1.38-6.61) and nearly 9-fold among persons without diabetes (95% CI, 6.41-12.46), compared with overweight. The adjusted RRs associated with diabetes varied by age and BMI, with the highest RR in young populations without obesity. Population attributable risks of invasive GBS disease were 27.2% for obesity and 40.1% for diabetes. Conclusions. Obesity and diabetes were associated with substantially increased risk of infection from invasive GBS. Given the population attributable risks of obesity and diabetes, interventions that reduce the prevalence of these conditions would likely reduce the burden of invasive GBS infection.