BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for esophageal squamous cell carcinoma (ESCC) in high-incidence areas of China, Iran and Brazil, but PAH assessments have not been conducted in East Africa, another ESCC hot spot. OBJECTIVE: To evaluate demographic or lifestyle factors associated with the PAH biomarker concentrations in the study population, and whether PAH metabolite concentrations showed any associations with esophageal precancerous lesions. METHODS: We recruited a community-based sample of 289 asymptomatic adults from a rural area of Kenya and performed Lugol's chromoendoscopy to detect esophageal squamous dysplasia (ESD); participants completed a questionnaire and provided a spot urine specimen. We analyzed urine for seven hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene at the U.S. National Center for Environmental Health, and compared creatinine-corrected PAH metabolite concentrations with questionnaire data and the presence of ESD. RESULTS: PAH metabolite concentrations among never tobacco users in these rural Kenya residents were 2.4-28.1 times higher than those reported from never tobacco users in Iran, Brazil and the USA. Female sex, cooking indoors, having no post-primary education, and age <50, but not tobacco use, were positively and significantly associated with PAH metabolite concentrations. Almost all participants used wood as cooking fuel. Nine participants had advanced ESD. Adjusted logistic regression showed a significant association between 2-hydroxynaphthalene (OR = 4.19, 95%CI: 1.01-17.47) and advanced ESD. All other PAH metabolites had positive but non-significant associations with advanced ESD. CONCLUSIONS: Urinary PAH metabolite concentrations among never tobacco users are markedly higher in this group from Kenya than in other populations and are associated with indoor cooking with wood on open, unvented stoves. These metabolite concentrations were also associated with the presence of advanced esophageal dysplasia. Our findings underline the importance of assessing alternative cooking conditions to reduce PAH exposure in this population.

BACKGROUND: Study A5274 was an open-label trial of people with HIV (PLHIV) with CD4 cell count <50 cells/µL who were randomized to empirical TB treatment vs. isoniazid preventive therapy (IPT) in addition to antiretroviral therapy (ART). We evaluated health-related quality of life (HRQoL) by study arm, changes over time, and association with sociodemographic and clinical factors.METHODS: Participants aged >13 years were enrolled from outpatient clinics in 10 countries. HRQoL was assessed at Weeks 0, 8, 24 and 96 with questions about daily activity, hospital or emergency room visits, and general health status. We used logistic regression to examine HRQoL by arm and association with sociodemographic and clinical factors.RESULTS: Among 850 participants (424 empiric arm, 426 IPT arm), HRQoL improved over time with no difference between arms. At baseline and Week 24, participants with WHO Stage 3 or 4 events, or those who had Grade 3 or 4 signs/symptoms, were significantly more likely to report poor HRQoL using the composite of four HRQoL measures.CONCLUSION: HRQoL improved substantially in both arms during the study period. These findings show that ART, TB screening, and IPT can not only reduce mortality, but also improve HRQoL in PLHIV with advanced disease.

ABSTRACT The inability to access health services when needed is a critical barrier to HIV prevention, treatment and care among men who have sex with men (MSM) and transgender women (TGW). Using data collected in HPTN 075, we explored factors associated with any experienced healthcare-related stigma. HPTN 075 was a cohort study to assess the feasibility of recruiting and retaining MSM and TGW in clinical trials in sub-Saharan Africa. Of 401 MSM and TGW enrolled at four sites (Kisumu, Kenya; Blantyre, Malawi; Cape Town, Soweto, South Africa) 397 contributed to the analysis (79.9% cis-gender and 20.1% TGW). Of these, (45.3%; 180/397) reported one or more of healthcare-related stigma experiences. Most frequently reported experiences included fear to seek healthcare services (36.3%) and avoiding seeking such services because of the discovery of MSM status (29.2%). Few men and TGW (2.5%) reported having been denied health services because of having sex with men. In multivariable analysis, more participants in Soweto [adjusted odds ratio (AOR) = 2.60] and fewer participants in Blantyre (AOR = 0.27) reported any healthcare-related stigma experiences, in comparison to participants in Kisumu. MSM and TGW that did not have a supportive gay community to rely on were more likely to report any healthcare-related stigma experiences (AOR = 1.46), whereas MSM and TGW who reported high social support and who never had engaged in transactional sex were less likely to report such experiences (AOR = 0.76 and AOR = 0.43, respectively). Our results suggest that encouraging support groups for MSM and TGW as well as training and sensitizing healthcare staff, and the general community, on MSM and TGW health issues and cultural competence may reduce stigma, improve access to healthcare, which could ultimately reduce HIV transmission.

SETTING: The household contacts (HHCs) of multidrug-resistant tuberculosis (MDR-TB) index cases are at high risk of tuberculous infection and disease progression, particularly if infected with the human immunodeficiency virus (HIV). HIV testing is important for risk assessment and clinical management. METHODS: This was a cross-sectional, multi-country study of adult MDR-TB index cases and HHCs. All adult and child HHCs were offered HIV testing if never tested or if HIV-negative >1 year previously when last tested. We measured HIV testing uptake and used logistic regression to evaluate predictors. RESULTS: A total of 1007 HHCs of 284 index cases were enrolled in eight countries. HIV status was known at enrolment for 226 (22%) HHCs; 39 (4%) were HIV-positive. HIV testing was offered to 769 (98%) of the 781 remaining HHCs; 544 (71%) agreed to testing. Of 535 who were actually tested, 26 (5%) were HIV-infected. HIV testing uptake varied by site (median 86%, range 0-100%; P < 0.0001), and was lower in children aged <18 years than in adults (59% vs. 78%; adjusted for site P < 0.0001). CONCLUSIONS: HIV testing of HHCs of MDR-TB index cases is feasible and high-yield, with 5% testing positive. Reasons for low test uptake among children and at specific sites-including sites with high HIV prevalence-require further study to ensure all persons at risk for HIV are aware of their status.

BACKGROUND: Anemia results in increased morbidity and mortality, underscoring the need to better understand its pathophysiology amongst HIV-exposed and infected children in sub-Saharan Africa, the region where most infant HIV exposure and infections occur. METHODS: This analysis used samples obtained from children in the Kisumu Breastfeeding Study (KiBS). KiBS was a longitudinal phase IIB, open-label, one-arm clinical trial, designed to investigate the safety, tolerability and effectiveness of a maternal triple-antiretroviral (ARV) regimen for prevention of mother-to-child transmission (PMTCT) of HIV, during late pregnancy and early infancy while breastfeeding. Blood samples from 482 children were obtained at birth, 2, 6, 10 and 14 weeks and 6, 9, 12, 18 and 24 months. Severity of anemia was graded using the NIH Division of AIDS (DAIDS) toxicity tables. We describe the proportion of children with anemia and anomalies in red blood cell parameters at various time points over 24 months and compare rates of anemia between HIV-infected and HIV-uninfected children and by mothers' ARV regimen and infant malaria infection. RESULTS: The proportion of children with anemia significantly increased after the breastfeeding period in both HIV-infected and HIV-uninfected children with higher proportion among HIV-infected children compared to HIV-uninfected children (RR: 1.72; CI: 1.22-2.44, p = 0.002). Maternal triple-antiretroviral regimen was not associated with infant anemia (p = 0.11). There was no significant difference in mean hemoglobin between HIV-uninfected children with and without malaria at each time point except at 24 months. CONCLUSION: A relatively lower proportion of children with severe anemia during the breastfeeding period suggest that exposure to mother's triple antiretroviral combinations through breast milk, posed minimal risk of hematologic toxicity.

BACKGROUND: In 2012, the World Health Organization (WHO) amended their 2010 guidelines for women receiving limited duration, triple-antiretroviral drug regimens during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (tARV-PMTCT) (Option B) to include the option to continue lifelong combination antiretroviral therapy (cART) (Option B+). We evaluated clinical and CD4 outcomes in women who had received antiretrovirals for prevention of mother-to-child transmission and then discontinued antiretrovirals 6-months postpartum. METHODS AND FINDINGS: The Kisumu Breastfeeding Study, 2003-2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT in ARV-naive, Kenyan women. Women received tARV-PMTCT from 34 weeks' gestation until 6-months postpartum when women were instructed to discontinue breastfeeding. Women with CD4 count (CD4) <250cells/mm3 or WHO stage III/IV prior to 6-months postpartum continued cART indefinitely. We estimated the change in CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for factors associated with declines in maternal CD4. We compared maternal and infant outcomes following weaning-when tARV-PMTCT discontinued-by maternal ARV status through 24-months postpartum. Compared with women who continued cART, discontinuing antiretrovirals was associated with infant HIV transmission and death (10.1% vs. 2.4%; P = 0.03). Among women who discontinued antiretrovirals, CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P = 0.002; aRR: 9.8; 95%-confidence interval [CI]: 2.4-40.6) or discontinuation (36.9% vs. 8.3%; P<0.0001; aRR: 4.4; 95%-CI: 1.9-5.0) were each associated with increased risk of women requiring cART for their own health within 6 months after discontinuing. CONCLUSIONS: Considering the serious health risks to the woman's infant and the brief reprieve from cART gained by stopping, every country should evaluate the need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at antiretroviral initiation or 6-months postpartum can identify pregnant women who would most benefit from continuing cART in settings unable to implement WHO Option B+.

In July 2011, a cluster of Yersinia enterocolitica infections was detected in southwestern Pennsylvania, USA. We investigated the outbreak's source and scope in order to prevent further transmission. Twenty-two persons were diagnosed with yersiniosis; 16 of whom reported consuming pasteurized dairy products from dairy A. Pasteurized milk and food samples were collected from this dairy. Y. enterocolitica was isolated from two products. Isolates from both food samples and available clinical isolates from nine dairy A consumers were indistinguishable by pulsed-field gel electrophoresis. Environmental and microbiological investigations were performed at dairy A and pasteurization deficiencies were noted. Because consumption of pasteurized milk is common and outbreaks have the potential to become large, public health interventions such as consumer advisories or closure of the dairy must be implemented quickly to prevent additional cases if epidemiological or laboratory evidence implicates pasteurized milk as the outbreak source.

HIV-1 drug resistance (HIVDR) assays are important tools in clinical management of HIV-infected patients on antiretroviral therapy (ART) and surveillance of drug-resistant variants at population levels. The high cost associated with commercial assays hinders their use in resource-limited settings. We adopted and validated a low-cost in-house assay using 68 matched plasma and dried blood spot (DBS) samples with a median viral load (VL) of 58,187 copies/ml, ranging from 253 to 3,264,850 against the commercial assay ViroSeq. Results indicated that the in-house assay not only had a higher plasma genotyping rate than did ViroSeq (94% versus 78%) but also was able to genotype 89.5% (51/57) of the matched DBS samples with VLs of ≥1,000 copies/ml. The sensitivity in detecting DR mutations by the in-house assay was 98.29% (95% confidence interval [CI], 97.86 to 98.72) on plasma and 96.54 (95% CI, 95.93 to 97.15) on DBS, and the specificity was 99.97% (95% CI, 99.91 to 100.00) for both sample types compared to ViroSeq. The minor DR mutation differences detected by the in-house assay against ViroSeq did not result in clinical significance. In addition, cost analysis showed that the in-house assay could reduce the genotyping cost by about 60% for both plasma and DBS compared to ViroSeq. This field condition evaluation highlights the potential utility of a cost-effective, subtype-independent, in-house genotyping assay using both plasma and DBS specimens for HIVDR clinical monitoring and population-based surveillance in resource-limited settings.

During August 2011, influenza A (H3N2) variant [A(H3N2)v] virus infection developed in a child who attended an agricultural fair in Pennsylvania, USA; the virus resulted from reassortment of a swine influenza virus with influenza A(H1N1)pdm09. We interviewed fair attendees and conducted a retrospective cohort study among members of an agricultural club who attended the fair. Probable and confirmed cases of A(H3N2)v virus infection were defined by serology and genomic sequencing results, respectively. We identified 82 suspected, 4 probable, and 3 confirmed case-patients who attended the fair. Among 127 cohort study members, the risk for suspected case status increased as swine exposure increased from none (4%; referent) to visiting swine exhibits (8%; relative risk 2.1; 95% CI 0.2-53.4) to touching swine (16%; relative risk 4.4; 95% CI 0.8-116.3). Fairs may be venues for zoonotic transmission of viruses with epidemic potential; thus, health officials should investigate respiratory illness outbreaks associated with agricultural events.

In 2006, area physicians reported increases in upper respiratory symptoms in patients living in FEMA-supplied trailers following Hurricanes Katrina and Rita. One potential etiology to explain their symptoms included formaldehyde; however, formaldehyde levels in these occupied trailers were unknown. The objectives of our study were to identify formaldehyde levels in occupied trailers and to determine factors or characteristics of occupied trailers that could affect formaldehyde levels. A disproportionate random sample of 519 FEMA-supplied trailers was identified in Louisiana and Mississippi in November 2007. We collected and tested an air sample from each trailer for formaldehyde levels and administered a survey. Formaldehyde levels among all trailers in this study ranged from 3 parts per billion (ppb) to 590 ppb, with a geometric mean of 77 ppb (95% confidence interval [CI]: 70-85; range: 3-590 ppb). There were statistically significant differences in formaldehyde levels between trailer types (p<0.01). The geometric mean formaldehyde level was 81 ppb (95% CI: 72-92) among travel trailers (n=360), 57 ppb (95% CI: 49-65) among mobile homes (n=57), and 44 ppb (95% CI: 38-53) among park models (n=44). Among travel trailers, formaldehyde levels varied significantly by brand. While formaldehyde levels varied by trailer type, all types tested had some levels ≥100 ppb. (Published 2012. This article is a U.S. Government work and is in the public domain in the USA.)

BACKGROUND: Few studies have evaluated the risk of nevirapine (NVP)-associated hepatotoxicity among HIV-infected pregnant women with a CD4 count ≥250 cells/mm(3). METHODS: We enrolled HIV-infected pregnant Kenyan women who initiated triple antiretroviral therapy (ART) at 34 weeks gestation. We compared the rates of severe hepatotoxicity (grades 3-4 hepatotoxicity) and rash-associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) with NVP and nelfinavir (NFV), respectively. RESULTS: We initiated triple ART in 522 pregnant women; severe hepatotoxicity and rash-associated hepatotoxicity occurred in 14 (3%) and 9 (2%) women, respectively. Women who initiated NVP had higher rates of severe hepatotoxicity (5% vs 1%; P = .03) and rash-associated hepatotoxicity (4% vs 0%; P = .003) when compared with NFV. Among women who initiated NVP (n = 254), a baseline CD4 count ≥250 cells/mm(3) was not associated with severe hepatotoxicity (5% vs 3%; P = .52) or rash-associated hepatotoxicity (4% vs 3%; P = .69). CONCLUSION: Nevirapine use but not CD4 count ≥250 cells/mm(3) was associated with hepatotoxicity.

Antiretroviral drugs cross from maternal plasma to breast milk and from breast milk to the infant in different concentrations. We measured concentrations of nelfinavir and its active metabolite (M8) in maternal plasma and breast milk from women and in dried blood spots collected from their infants at delivery and postnatal weeks 2, 6, 14, and 24 in the Kisumu Breastfeeding Study, Kisumu, Kenya. Nelfinavir-based antiretroviral regimens given to mothers as PMTCT do not expose the breastfeeding infant to biologically significant concentrations of nelfinavir or M8.

BACKGROUND: Poison control centers and clinical toxicologists serve many roles within public health; however, the degree to which these entities collaborate is unknown. PURPOSE: The objective of this survey was to identify successful collaborations of public health agencies with clinical toxicologists and poison control centers. Four areas including outbreak identification, syndromic surveillance, terrorism preparedness, and daily public health responsibilities amenable to poison control center resources were assessed. METHODS: An online survey was sent to the directors of poison control centers, state epidemiologists, and the most senior public health official in each state and selected major metropolitan areas. This survey focused on three areas: service, structure within the local or state public health system, and remuneration. Questions regarding remuneration and poison control center location within the public health structure were asked to assess if these were critical factors of successful collaborations. Senior state and local public health officials were excluded because of a low response rate. The survey was completed in October 2007. RESULTS: A total of 111 respondents, 61 poison control centers and 50 state epidemiologists, were eligible for the survey. Sixty-nine (62%) of the 111 respondents, completed and returned the survey. Thirty-three (54%) of the 61 poison control centers responded, and 36 of the 50 state epidemiologists (72%) responded. The most frequent collaborations were terrorism preparedness and epidemic illness reporting. Additional collaborations also exist. Important collaborations exist outside of remuneration or poison control centers being a formal part of the public health structure. CONCLUSIONS: Poison control centers have expanded their efforts to include outbreak identification, syndromic surveillance, terrorism preparedness, and daily public health responsibilities amenable to poison control center resources. Collaboration in these areas and others should be expanded.

BACKGROUND: Department of Transportation (DOT) mandates reporting of all serious hazardous materials incidents. Hazardous material exposures may result in secondary contamination of emergency departments, or delayed clinical effects. Poison control centers specialize in the management of patients exposed to toxic substances; however, poison control center notification is not required. PURPOSE: The objective is to determine the frequency of poison control center notification after serious hazardous materials incidents when patients were transported to a hospital. METHODS: A retrospective analysis was conducted of serious hazardous materials incidents as reported by DOT, matched with data from the American Association of Poison Control Centers from 2002 through 2006 that involved patient transport. Incidents were divided into four groups: those reported to a poison control center within 0-360 minutes of the incident; those reported within 361-1440 minutes of the incident; those reported within 1441-4320 minutes of the incident; and no poison control center notification. Analyses were performed on variables including date, time, substance, and time to notification. Data were received in January 2008. RESULTS: One hundred fifty-four serious incidents met inclusion criteria. One hundred thirty-four incidents (87%) occurred without poison control center notification. Poison control centers were notified in 20 incidents (12.9%); 15 incidents (9.7%) were reported within 0-360 minutes of the incident (M=115 minutes, range=5-359 minutes); four incidents (2.6%) were reported within 361-1440 minutes of the incident (M=652 minutes, range=566-750 minutes); and one incident (0.7%) was reported after 4320 minutes following the incident. CONCLUSIONS: Most serious hazardous materials incidents involving patient transport are not reported to poison control centers. Opportunities exist to increase utilization of poison control center resources without increasing financial burdens of the hazardous materials incident.