Food Insecurity at HIV Diagnosis Associated with Subsequent Viremia Amongst Adults Living with HIV in an Urban Township of South Africa.

We assessed the temporal impact of food insecurity on 12-month antiretroviral (ART) adherence, retention in care, hospitalization, and HIV viremia (> 1000 copies/mL) in ART naïve adults presenting for HIV testing in Umlazi, South Africa. At the time of HIV testing and prior to ART initiation, we determined each participants' food security status using the validated Household Food Insecurity Access Scale (HFIAS). Following HIV testing and ART initiation, we then assessed the above outcomes of each study participant at 3-month intervals for a total of 12 months. Among 2,383 participants with HIV in this study, 253 (10.6%) experienced food insecurity. We found that food insecurity is associated with 20% higher adjusted prevalence odd ratios (aPOR) of having HIV viremia (> 1000 copies/mL) at 12 months following initial diagnosis (aPOR 1.2, 95% CI 1.1-1.4). We found no significant differences in ART adherence, retention in care, and hospitalization occurrences between the food secure and food insecure cohorts.

Symbolic and anticipated HIV stigma are associated with mental health and education in South Africa.

HIV stigma continues to act as a barrier to HIV care in South Africa, necessitating further research on the intersections of socioeconomic factors and the anticipation and expression of stigma surrounding HIV. We measured the prevalence of HIV-related stigma and evaluated factors associated with symbolic and anticipated stigma in Umlazi Township, South Africa from 2013 to 2019, using a validated HIV stigma scale, before undergoing HIV testing. Among 7,724 people evaluated, 1,318 (16.9%) reported symbolic stigma and 2,396 (30.8%) anticipated HIV stigma. Prevalence of symbolic and anticipated stigma were significantly more common among both women and people living with HIV, compared to men and those who tested negative for HIV. In multivariable analyses, higher education and depressive symptoms were the strongest correlates with both symbolic stigma and anticipated stigma. Younger age, not being married, and having a partner who was not living with HIV appeared to be important correlates with anticipated stigma, but not symbolic stigma. Overall, the anticipation of experiencing stigma because of infection with HIV continues to be an important factor in the testing and management of HIV.

Effect of perceived HIV risk on initiation of antiretroviral therapy during the universal test and treat era in South Africa.

BACKGROUND: South Africa has not achieved the 90-90-90 goals, in part due to low rates of antiretroviral therapy (ART) initiation among those aware of their HIV status. Perceived risk of HIV at the time of testing may affect likelihood of rapid ART initiation. The purpose of this study was to evaluate factors associated with perceived risk of HIV and the relationship between perceived HIV risk and rapid ART initiation during the universal test and treat era which was adapted in October 2016. METHODS: We conducted a prospective study of adults undergoing HIV testing from October 2016-February 2019 at Ithembalabantu Clinic in Durban. Eligible participants reported not previously being diagnosed with HIV. Before HIV testing, participants were asked to assess their perceived HIV risk on a four-level scale. We categorized "definitely not" and "probably not going to acquire HIV" as a low perceived risk, and "probably will" and "definitely will become HIV-infected" as a high perceived risk of HIV infection. Participants were followed for up to 14 months following HIV testing to assess ART initiation. RESULTS: Among 1519 people newly diagnosed with HIV, 55% were female and mean age was 33 years. Among those, 1382 (90.9%) had a high HIV risk perception and 137 (9.1%) reported low HIV risk perception. In the low risk group individuals were more likely to be female (58% vs 55%), unemployed (62% vs 59%), have a partner with unknown HIV status (61% vs 55%) compared to the high risk group. 83.2% of those with low HIV risk perception reported previously HIV testing compared 91.5% of those with high HIV risk perception. In the multivariate model, males were associated with a higher chances of initiating ART compared to females (adjusted hazard ratio (aHR): 1.187, CI 1.187 (1.060-1.329) and being unemployed (aHR 0.767 CI (0.650-0.905). Those with a low HIV risk perception were less likely to initiate ART 125 (91%) vs 1310 (95%) p = 0.022), and took longer to initiate on ART after HIV diagnosis (11 days' vs 4 days, p = 0.042). CONCLUSION: Factors associated with high HIV risk perception included being unemployed, single, and having a partner of unknown HIV status. People living with HIV (PLHIV) in South Africa who had a low self-perceived risk to HIV infection were less likely to initiate ART. Assessing self-perceived risk of HIV infection may help direct counselling and improve ART initiation to achieve universal 90-90-90 goal.

Clinic-based diabetes screening at the time of HIV testing and associations with poor clinical outcomes in South Africa: a cohort study.

BACKGROUND: HIV clinical care programs in high burden settings are uniquely positioned to facilitate diabetes diagnosis, which is a major challenge. However, in sub-Saharan Africa, data on the burden of diabetes among people living with HIV (PLHIV) and its impact on HIV outcomes is sparse. METHODS: We enrolled adults presenting for HIV testing at an outpatient clinic in Durban. Those who tested positive for HIV-infection were screened for diabetes using a point-of-care hemoglobin A1c (HbA1c) test. We used log-binomial, Poisson, and Cox proportional hazard models adjusting for confounders to estimate the relationship of diabetes (HbA1c ≥ 6.5%) with the outcomes of HIV viral suppression (< 50 copies/mL) 4-8 months after antiretroviral therapy initiation, retention in care, hospitalization, tuberculosis, and death over 12 months. RESULTS: Among 1369 PLHIV, 0.5% (n = 7) reported a prior diabetes diagnosis, 20.6% (95% CI 18.5-22.8%, n = 282) screened positive for pre-diabetes (HbA1c 5.7-6.4%) and 3.5% (95% CI 2.7-4.6%, n = 48) for diabetes. The number needed to screen to identify one new PLHIV with diabetes was 46.5 persons overall and 36.5 restricting to those with BMI ≥ 25 kg/m2. Compared to PLHIV without diabetes, the risk of study outcomes among those with diabetes was not statistically significant, although the adjusted hazard of death was 1.79 (95% CI 0.41-7.87). CONCLUSIONS: Diabetes and pre-diabetes were common among adults testing positive for HIV and associated with death. Clinic-based diabetes screening could be targeted to higher risk groups and may improve HIV treatment outcomes.

Cryptococcal antigenemia is associated with meningitis or death in HIV-infected adults with CD4 100-200 cells/mm3.

BACKGROUND: Cryptococcal antigen (CrAg) screening with fluconazole prophylaxis has been shown to prevent cryptococcal meningitis and mortality for people living with HIV (PLWH) with CD4 < 100 cells/mm3. While cryptococcal meningitis occurs in individuals with CD4 100-200 cells/mm3, there is limited evidence that CrAg screening predicts cryptococcal meningitis or mortality among this group with moderate immunosuppression. Current IDSA and WHO clinical guidelines recommend restricting CrAg screening to PLWH with CD4 < 100 cells/mm3. METHODS: We conducted a prospective cohort study of PLWH 18+ years who had not initiated ART in South Africa. We followed participants for 14 months to determine onset of cryptococcal meningitis or all-cause mortality. At study completion, we retrospectively tested stored serum samples for CrAg using an enzyme immunoassay (EIA). We calculated CD4-stratified incidence rates of outcomes and used Cox proportional hazards to measure associations between CrAg positivity and outcomes. RESULTS: We enrolled 2383 PLWH, and 1309 participants had serum samples tested by CrAg EIA. The median CD4 was 317 cells/mm3 (interquartile range: 173-491 cells/mm3). By CD4 count at baseline, there were 209 individuals with a CD4 count of 100-200 cells/mm3 and available CrAg test results. Of these, four (1.9%) tested positive. Two of four (IR: 58.8 per 100 person-years) CrAg+ participants and 11 of 205 (IR: 5.6 per 100 person-years) CrAg- participants developed cryptococcal meningitis or died for an overall rate of death or cryptococcal meningitis that was 10.0-times higher for those who were CrAg+ (95% confidence interval: 2.2-45.3). Among those with CD4 < 100 cell/mm3 and CrAg EIA test results (N = 179), ten (5.6%) participants tested CrAg+. Among this group, seven of ten (IR: 137.6 per 100 person-years) CrAg+ participants and 26 of 169 (IR: 17.8 per 100 person-years) CrAg- participants developed cryptococcal meningitis or died, for a rate of death or cryptococcal meningitis that was 6.3-times higher for those who were CrAg+ (95% confidence interval: 2.7-14.6). CONCLUSIONS: Although few PLWH with moderate immunosuppression screened CrAg positive, a positive CrAg test was predictive of increased risk of cryptococcal meningitis or death. Similar to those with a CD4 < 100 cell/mm3, systematic CrAg screening may reduce morbidity and mortality in PLWH with CD4 100-200 cells/mm3.

A national evaluation using standardised patient actors to assess STI services in public sector clinical sentinel surveillance facilities in South Africa.

OBJECTIVES: Quality concerns in STI service delivery and missed opportunities for integration with HIV testing and prevention services in South Africa have been well documented. This national evaluation aimed to evaluate current utilisation and adherence to national STI guidelines, including partner notification and integration with HIV services, for diagnosis and management of STIs. METHODS: Facility surveys assessed infrastructure and resource availability, and standardised patient (SP) assessments evaluated quality of STI care in 50 public clinics in nine provinces in South Africa. The primary outcome was the proportion of SPs receiving essential STI care, defined as: offered an HIV test, condoms, partner notification counselling and correct syndromic treatment. Weighted proportions were generated, and SP findings were compared by gender using χ2 tests with Rao-Scott correction. RESULTS: More than 80% of facilities reported medications in stock, with the exceptions of oral cefixime (48.3%), oral erythromycin (75.1%) and paediatric syrups. Among 195 SP encounters, 18.7% (95% CI 10.7% to 30.5%) received all hypothesised essential STI services: offered HIV test (67.1%), offered condoms (31.4%), partner notification counselling (70.2%) and recommended syndromic treatment (60.7%). Men were more likely than women to be offered all services (25.1% vs 12.3%, p=0.023), recommended treatment (70.7% vs 50.9%, p=0.013) and partner notification counselling (79.9% vs 60.6%, p=0.020). Only 6.3% of providers discussed male circumcision with male SPs, and 26.3% discussed family planning with female SPs. CONCLUSIONS: This evaluation of STI services across South Africa found gaps in the availability of medications, adherence to STI guidelines, condom provision and prevention messaging. Limited integration with HIV services for this high-risk population was a missed opportunity. Quality of STI care should continue to be monitored, and interventions to improve quality should be prioritised as part of national strategic HIV and primary healthcare agendas.

Three methods of delivering clinic-based training on syndromic management of sexually transmitted diseases in South Africa: a pilot study.

INTRODUCTION: The South African National Department of Health sought to improve syndromic management of sexually transmitted infections (STIs). Continuing medical education on STIs was delivered at primary healthcare (PHC) clinics using one of three training methods: (1) lecture, (2) computer and (3) paper-based. Clinics with training were compared with control clinics. METHODS: Ten PHC clinics were randomly assigned to control and 10 to each training method arm. Clinicians participated in on-site training on six modules; two per week for three weeks. Each clinic was visited by three or four unannounced standardised patient (SP) actors pre-training and post-training. Male SPs reported symptoms of male urethritis syndrome and female SPs reported symptoms of vaginal discharge syndrome. Quality of healthcare was measured by whether or not clinicians completed five tasks: HIV test, genital exam, correct medications, condoms and partner notification. RESULTS: An average of 31% of clinicians from each PHC attended each module. Quality of STI care was low. Pre-training (n=128) clinicians completed an average of 1.63 tasks. Post-training (n=114) they completed 1.73. There was no change in the number of STI tasks completed in the control arm and an 11% increase overall in the training arms relative to the control (ratio of relative risk (RRR)=1.11, 95% CI 0.67 to 1.84). Across training arms, there was a 26% increase (RRR=1.26, 95% CI 0.77 to 2.06) associated with lecture, 17% increase (RRR=1.17, 95% CI 0.59 to 2.28) with paper-based and 13% decrease (RRR=0.87, 95% CI 0.40 to 1.90) with computer arm relative to the control. CONCLUSIONS: Future interventions should address increasing training attendance and computer-based training effectiveness. TRIAL REGISTRATION NUMBER: AEARCTR-0000668.

Prevalence of functional difficulty among school-aged children and effect on school enrolment in rural southern India: A cross-sectional analysis.

Despite the large number of children in India, there is little information on the impact of children's disability on school enrolment, and how this differs by population. We estimated the prevalence of childhood disability in two sites in Tamil Nadu, southern India, and the effect of functional difficulty on school enrolment. We used a parent-reported survey containing the UNICEF-Washington Group questions to identify children aged 5 to 17 years with functional difficulty during a census conducted for an ongoing trial. We estimated pooled- and gender-specific prevalence of functional difficulty among 29,044 children. We fitted regression models to identify subgroups with higher rates of functional difficulty and the effect of functional difficulty on reported school enrolment. We estimated the modification of the effect of functional difficulty by age, gender, socioeconomic status, household education, and sub-site, on additive and multiplicative scales. We found of 29,044 children, 299 (1.0%) had any functional difficulty, equal among boys and girls. Being understood (0.5%) and walking (0.4%) were the most common difficulties. Functional difficulty was strongly associated with non-enrolment in school (Prevalence ratio [PR] 4.59, 95% CI: 3.87, 5.43) after adjusting for age, gender, and site. We show scale-dependent differences between age and socioeconomic groups in the effect of functional difficulty on enrolment. This study shows that at least one in a hundred children in this region have severe functional difficulties and nearly half of these children are not enrolled in school, highlighting the need for further efforts and evidence-based interventions to increase school enrolment among these groups.

Data Management in Multicountry Consortium Studies: The Enterics For Global Health (EFGH) Shigella Surveillance Study Example.

Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study-a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella--associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data.

Diarrhea Case Surveillance in the Enterics for Global Health Shigella Surveillance Study: Epidemiologic Methods.

Background: Shigella is a leading cause of acute watery diarrhea, dysentery, and diarrhea-attributed linear growth faltering, a precursor to stunting and lifelong morbidity. Several promising Shigella vaccines are in development and field efficacy trials will require a consortium of potential vaccine trial sites with up-to-date Shigella diarrhea incidence data. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will employ facility-based enrollment of diarrhea cases aged 6-35 months with 3 months of follow-up to establish incidence rates and document clinical, anthropometric, and financial consequences of Shigella diarrhea at 7 country sites (Mali, Kenya, The Gambia, Malawi, Bangladesh, Pakistan, and Peru). Over a 24-month period between 2022 and 2024, the EFGH study aims to enroll 9800 children (1400 per country site) between 6 and 35 months of age who present to local health facilities with diarrhea. Shigella species (spp.) will be identified and serotyped from rectal swabs by conventional microbiologic methods and quantitative polymerase chain reaction. Shigella spp. isolates will undergo serotyping and antimicrobial susceptibility testing. Incorporating population and healthcare utilization estimates from contemporaneous household sampling in the catchment areas of enrollment facilities, we will estimate Shigella diarrhea incidence rates. Conclusions: This multicountry surveillance network will provide key incidence data needed to design Shigella vaccine trials and strengthen readiness for potential trial implementation. Data collected in EFGH will inform policy makers about the relative importance of this vaccine-preventable disease, accelerating the time to vaccine availability and uptake among children in high-burden settings.

Shigella Detection and Molecular Serotyping With a Customized TaqMan Array Card in the Enterics for Global Health (EFGH): Shigella Surveillance Study.

Background: Quantitative polymerase chain reaction (qPCR) targeting ipaH has been proven to be highly efficient in detecting Shigella in clinical samples compared to culture-based methods, which underestimate Shigella burden by 2- to 3-fold. qPCR assays have also been developed for Shigella speciation and serotyping, which is critical for both vaccine development and evaluation. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will utilize a customized real-time PCR-based TaqMan Array Card (TAC) interrogating 82 targets, for the detection and differentiation of Shigella spp, Shigella sonnei, Shigella flexneri serotypes, other diarrhea-associated enteropathogens, and antimicrobial resistance (AMR) genes. Total nucleic acid will be extracted from rectal swabs or stool samples, and assayed on TAC. Quantitative analysis will be performed to determine the likely attribution of Shigella and other particular etiologies of diarrhea using the quantification cycle cutoffs derived from previous studies. The qPCR results will be compared to conventional culture, serotyping, and phenotypic susceptibility approaches in EFGH. Conclusions: TAC enables simultaneous detection of diarrheal etiologies, the principal pathogen subtypes, and AMR genes. The high sensitivity of the assay enables more accurate estimation of Shigella-attributed disease burden, which is critical to informing policy and in the design of future clinical trials.

Microbiological Methods Used in the Enterics for Global Health Shigella Surveillance Study.

Background: Shigella is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting Shigella are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings. Here, we describe the microbiological methods used to isolate and identify Shigella. We developed a standardized laboratory protocol for isolation and identification of Shigella by culture. This protocol was implemented across all 7 sites, ensuring consistency and comparability of results. Secondary objectives of the study are to determine the antibiotic resistance profiles of Shigella, compare isolation of Shigella from rectal swabs versus whole stool, and compare isolation of Shigella following transport of rectal swabs in Cary-Blair versus a modified buffered glycerol saline transport medium. Conclusions: Data generated from EFGH using culture methods described herein can potentially be used for microbiological endpoints in future phase 3 clinical trials to evaluate vaccines against shigellosis and for other clinical and public health studies focused on these organisms.

Population Enumeration and Household Utilization Survey Methods in the Enterics for Global Health (EFGH): Shigella Surveillance Study.

Background: Accurate estimation of diarrhea incidence from facility-based surveillance requires estimating the population at risk and accounting for case patients who do not seek care. The Enterics for Global Health (EFGH) Shigella surveillance study will characterize population denominators and healthcare-seeking behavior proportions to calculate incidence rates of Shigella diarrhea in children aged 6-35 months across 7 sites in Africa, Asia, and Latin America. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will use a hybrid surveillance design, supplementing facility-based surveillance with population-based surveys to estimate population size and the proportion of children with diarrhea brought for care at EFGH health facilities. Continuous data collection over a 24 month period captures seasonality and ensures representative sampling of the population at risk during the period of facility-based enrollments. Study catchment areas are broken into randomized clusters, each sized to be feasibly enumerated by individual field teams. Conclusions: The methods presented herein aim to minimize the challenges associated with hybrid surveillance, such as poor parity between survey area coverage and facility coverage, population fluctuations, seasonal variability, and adjustments to care-seeking behavior.

Representativeness of a mobile phone-based coverage evaluation survey following mass drug administration for soil-transmitted helminths: a comparison of participation between two cross-sectional surveys.

OBJECTIVES: With increasing mobile phone subscriptions, phone-based surveys are gaining popularity with public health programmes. Despite advantages, systematic exclusion of participants may limit representativeness. Similar to control programmes for neglected tropical diseases (NTDs), the DeWorm3 trial of biannual community-wide mass drug administration (MDA) for elimination of soil-transmitted helminth infection used in-person coverage evaluation surveys to measure the proportion of the at-risk population treated during MDA. Due to lockdown during the COVID-19 pandemic, a phone-based coverage evaluation survey was necessary, providing an opportunity for the current study to compare representativeness and implementation (including non-response) of these two survey modes. DESIGN: Comparison of two cross-sectional surveys. SETTING: The DeWorm3 trial site in Tamil Nadu, India, includes Timiri, a rural subsite, and Jawadhu Hills, a hilly, hard-to-reach subsite inhabited predominantly by a tribal population. PARTICIPANTS: In the phone-based and in-person coverage evaluation surveys, all individuals residing in 2000 randomly selected households (50 in each of the 40 trial clusters) were eligible to participate. Here, we characterise household participation. RESULTS: Of 2000 households, 1780 (89.0%) participated during the in-person survey. Of 2000 households selected for the phone survey, 346 (17.3%) could not be contacted as they had not provided a telephone number during the census and 1144 (57.2%) participated. Smaller households, households with lower socioeconomic status and those with older, women or less educated household-heads were under-represented in the phone-based survey compared with censused households. Regression analysis revealed non-response in the phone-based survey was higher among households from the poorest socioeconomic quintile (prevalence ratio (PR) 2.3, 95% CI 2.0 to 2.7) and lower when heads of households had completed secondary school or higher education (PR 0.7, 95% CI 0.6 to 0.8). CONCLUSIONS: Our findings suggest phone-based surveys under-represent households likely to be at higher risk of NTDs and in-person surveys are more appropriate for measuring MDA coverage within programmatic settings. TRIAL REGISTRATION NUMBER: NCT03014167.

Overestimation of school-based deworming coverage resulting from school-based reporting.

BACKGROUND: Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years (DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the World Health Organization to reduce levels of morbidity due to STH in endemic areas. DeWorm3 is a cluster-randomized trial, conducted in three study sites in Benin, India, and Malawi, designed to assess the feasibility of interrupting STH transmission with community-wide MDA as a potential strategy to replace SBD. This analysis examines data from the DeWorm3 trial to quantify discrepancies between school-level reporting of SBD and gold standard individual-level survey reporting of SBD. METHODOLOGY/PRINCIPAL FINDINGS: Population-weighted averages of school-level SBD calculated at the cluster level were compared to aggregated individual-level SBD estimates to produce a Mean Squared Error (MSE) estimate for each study site. In order to estimate individual-level SBD coverage, these MSE values were applied to SBD estimates from the control arm of the DeWorm3 trial, where only school-level reporting of SBD coverage had been collected. In each study site, SBD coverage in the school-level datasets was substantially higher than that obtained from individual-level datasets, indicating possible overestimation of school-level SBD coverage. When applying observed MSE to project expected coverages in the control arm, SBD coverage dropped from 89.1% to 70.5% (p-value < 0.001) in Benin, from 97.7% to 84.5% (p-value < 0.001) in India, and from 41.5% to 37.5% (p-value < 0.001) in Malawi. CONCLUSIONS/SIGNIFICANCE: These estimates indicate that school-level SBD reporting is likely to significantly overestimate program coverage. These findings suggest that current SBD coverage estimates derived from school-based program data may substantially overestimate true pediatric deworming coverage within targeted communities. TRIAL REGISTRATION: NCT03014167.

Multiple overlapping risk factors for childhood wheeze among children in Benin.

BACKGROUND: The African continent is currently facing an epidemiological transition characterized by a shift from communicable to non-communicable diseases. Prominent amongst the latter are allergies and asthma. In that context, wheeze has multiple potential contributory factors that could include some of the endemic helminth infections, as well as environmental exposures, such as household air pollution. We sought to determine the relative importance of these risk factors among children in Benin. METHODS: We included 964 children aged 6-14 years living in the commune of Comé, south-west Benin. All children were participants in the longitudinal monitoring cohort of the DeWorm3 trial designed to evaluate multiple rounds of community mass treatment with albendazole for interruption of the transmission of soil transmitted helminths (STH). We administered a standard ISAAC questionnaire to determine the presence of wheeze. In addition, we assessed exposure to household air pollution and to other potential allergy-inducing factors, dietary intake and anthropometry. Using STH infection status assessed at the pretreatment baseline timepoint, we used multivariate statistical modelling, controlling for covariates, to investigate associations between wheeze and the different factors measured. RESULTS: The prevalence of wheezing history was 5.2%, of current wheezing was 4.6% and of severe wheezing was 3.1%, while STH infections were found in 5.6% of children. These profiles did not vary as a function of either age or gender. Infection with Ascaris lumbricoides, but not hookworm species, was significantly associated with both current wheeze (adjusted Odds Ratio (aOR) = 4.3; 95% CI [1.5-12.0]) and severe wheeze (aOR = 9.2; 95% CI [3.1-27.8]). Significant positive associations with current wheeze, independent of each other and of STH infection status, were also found for (i) use of open cookstoves (aOR = 3.9; 95% CI [1.3-11.5]), (ii) use of palm cakes for fire lighting (aOR = 3.4; 95% CI [1.1-9.9]), (iii) contact with domestic animals and/or rodents (aOR = 2.5; 95% CI [1.1-6.0]), (iv) being overweight (aOR = 9.7; 95% CI [1.7-55.9]). Use of open cookstoves and being overweight were also independent risk factors for severe wheeze (aOR = 3.9; 95% CI [1.1-13.7]) and aOR = 10.3; 95% CI [1.8-60.0], respectively). CONCLUSIONS: Children infected with A. lumbricoides appear to be at elevated risk of wheeze. Deworming may be an important intervention to reduce these symptoms. Improving cooking methods to reduce household air pollution, modifying dietary habits to avoid overweight, and keeping animals out of the house are all additional measures that could also contribute to reducing childrens' risk of wheeze. Policymakers in LMIC should consider tailoring public health measures to reflect the importance of these different risk factors.

Adaptive responses to purine starvation in Leishmania donovani.

Starvation of Leishmania donovani parasites for purines leads to a rapid amplification in purine nucleobase and nucleoside transport. Studies with nucleoside transport-deficient L. donovani indicate that this phenomenon is mediated by the nucleoside transporters LdNT1 and LdNT2, as well as by the purine nucleobase transporter LdNT3. The escalation in nucleoside transport cannot be ascribed to an increase in either LdNT1 or LdNT2 mRNA. However, Western analyses on parasites expressing epitope-tagged LdNT2 revealed a marked upregulation in transporter protein at the cell surface. Kinetic investigations of LdNT1 and LdNT2 activities from purine-replete and purine-starved cells indicated that both transporters exhibited significant increases in V(max) for their ligands under conditions of purine-depletion, although neither transporter displayed an altered affinity for its respective ligands. Concomitant with the increase in purine nucleoside and nucleobase transport, the purine salvage enzymes HGPRT, XPRT and APRT were also upregulated, suggesting that under conditions where purines are limiting, Leishmania parasites remodel their purine metabolic pathway to maximize salvage. Moreover, qRT-PCR analyses coupled with cycloheximide inhibition studies suggest that the underlying molecular mechanism for this augmentation in purine salvage occurs post-transcriptionally and is reliant on de novo protein synthesis.

Depression and anxiety as barriers to art initiation, retention in care, and treatment outcomes in KwaZulu-Natal, South Africa.

BACKGROUND: Since mental health may influence HIV care among people living with HIV (PLHIV), we sought to evaluate the impact of anxiety and depression on ART initiation and HIV-related outcomes. METHODS: We conducted a prospective cohort study of PLHIV in the Umlazi Township of KwaZulu-Natal, South Africa. We measured depression using the Patient Health Questionnaire (PHQ-9) and anxiety using the Generalized Anxiety Disorder (GAD-7) scale, both of which have been validated in sub-Saharan Africa, among all patients prior to receiving a positive HIV test. We then followed those who tested HIV+ for 12 months to determine their time to ART initiation, missing clinic visits or refills, retention in care, hospitalization, and death. We used logistic regression models, adjusted for socio-demographic characteristics such as age and sex, to examine the effects of baseline measures of depression and anxiety on ART initiation and HIV treatment outcomes. FINDINGS: Among 2,319 adult PLHIV, mean age was 33 years (SD=9.3 years), 57% were female, and baseline median CD4 count was 317 cells/mm3 (IQR=175-491 cells/mm3). In univariate analyses, depression was associated with slower rates of ART initiation. In adjusted models, PLHIV with depression had lower odds of initiating ART within 90 days of HIV testing (aOR=0.60, 95% CI=0.46, 0.79, p<0.01), and lower odds of being retained in care (aOR=0.77, 95% CI=0.60, 0.99, p = 0.04). By the end of the 12-month study period, odds of ART initiation among PLHIV with depression were higher than the first 90 days but still significantly lower compared to those without depression (aOR=0.72, 95% CI=0.52, 0.99, p = 0.04). Among PLHIV who initiated ART, depression was associated with a lower odds of missing clinic visits (aOR=0.54, 95% CI= 0.40, 0.73, p<0.01). Anxiety was strongly correlated with depression (r = 0.77, p<0.01) and had similar effects on HIV-related outcomes. INTERPRETATIONS: The presence of depression is a significant barrier to ART initiation and retention in care among adult PLHIV in South Africa. Mental health screenings around the time of HIV testing may help improve linkage and HIV-related outcomes. FUNDING: This work was supported by the Infectious Disease Society of America Education & Research Foundation and National Foundation for Infectious Diseases (PKD); Massachusetts General Hospital Executive Committee on Research (PKD); the Harvard University Center for AIDS Research [AI060354] (PKD); and the National Institute of Allergy and Infectious Diseases [AI108293, AI143351] (PKD). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or other funding agencies.

Laboratory Reflex and Clinic-Based Point-of-Care Cryptococcal Antigen Screening for Preventing Meningitis and Mortality Among People Living With HIV.

INTRODUCTION: Cryptococcosis remains a leading cause of meningitis and mortality among people living with HIV (PLHIV) worldwide. We sought to evaluate laboratory-based cryptococcal antigen (CrAg) reflex testing and a clinic-based point-of-care (POC) CrAg screening intervention for preventing meningitis and mortality among PLHIV in South Africa. METHODS: We conducted a prospective pre-post intervention study of adults presenting for HIV testing in Umlazi township, South Africa, over a 6-year period (2013-2019). Participants were enrolled during 3 phases of CrAg testing: CrAg testing ordered by a clinician (clinician-directed testing, 2013-2015); routine laboratory-based CrAg reflex testing for blood samples with CD4 ≤100 cells/mm3 (laboratory reflex testing, 2015-2017); and a clinic-based intervention with POC CD4 testing and POC CrAg testing for PLHIV with CD4 ≤200 cells/mm3 with continued standard-of-care routine laboratory reflex testing among those with CD4 ≤100 cells/mm3 (clinic-based testing, 2017-2019). The laboratory and clinical teams performed serum CrAg by enzyme immunoassay and lateral flow assay (Immy Diagnostics, Norman, OK). We followed up participants for up to 14 months to compare associations between baseline CrAg positivity, antiretroviral therapy and fluconazole treatment initiation, and outcomes of cryptococcal meningitis, hospitalization, and mortality. RESULTS: Three thousand one hundred five (39.4%) of 7877 people screened were HIV-positive, of whom 908 had CD4 ≤200 cells/mm3 and were included in the analyses. Laboratory reflex and clinic-based testing increased CrAg screening (P < 0.001) and diagnosis of CrAg-positive PLHIV (P = 0.011). When compared with clinician-directed testing, clinic-based CrAg testing showed an increase in the number of PLHIV diagnosed with cryptococcal meningitis (4.5% vs. 1.5%; P = 0.059), initiation of fluconazole preemptive therapy (7.2% vs. 2.5%; P = 0.010), and initiation of antiretroviral therapy (96.8% vs. 91.3%; P = 0.012). Comparing clinic-based testing with laboratory reflex testing, there was no significant difference in the cumulative incidence of cryptococcal meningitis (4.5% vs. 4.1%; P = 0.836) or mortality (8.1% vs. 9.9%; P = 0.557). CONCLUSIONS: Laboratory reflex and clinic-based CrAg testing facilitated the diagnosis of HIV-associated cryptococcosis and fluconazole initiation but did not reduce cryptococcal meningitis or mortality. In this nonrandomized cohort, clinical outcomes were similar between laboratory reflex testing and clinic-based POC CrAg testing.

Factors associated with soil-transmitted helminths infection in Benin: Findings from the DeWorm3 study.

BACKGROUND: Despite several years of school-based MDA implementation, STH infections remain an important public health problem in Benin, with a country-wide prevalence of 20% in 2015. The DeWorm3 study is designed to assess the feasibility of using community-based MDA with albendazole to interrupt the transmission of STH, through a series of cluster-randomized trials in Benin, India and Malawi. We used the pre-treatment baseline survey data to describe and analyze the factors associated with STH infection in Comé, the study site of the DeWorm3 project in Benin. These data will improve understanding of the challenges that need to be addressed in order to eliminate STH as a public health problem in Benin. METHODS: Between March and April 2018, the prevalence of STH (hookworm spp., Ascaris and Trichuris trichiura) was assessed by Kato-Katz in stool samples collected from 6,153 residents in the community of Comé, Benin using a stratified random sampling procedure. A standardized survey questionnaire was used to collect information from individual households concerning factors potentially associated with the presence and intensity of STH infections in pre-school (PSAC, aged 1-4), school-aged children (SAC, aged 5-14) and adults (aged 15 and above). Multilevel mixed-effects models were used to assess associations between these factors and STH infection. RESULTS: The overall prevalence of STH infection was 5.3%; 3.2% hookworm spp., 2.1% Ascaris lumbricoides and 0.1% Trichuris. Hookworm spp. were more prevalent in adults than in SAC (4.4% versus 2.0%, respectively; p = 0.0001) and PSAC (4.4% versus 1.0%, respectively; p<0.0001), whilst Ascaris lumbricoides was more prevalent in SAC than in adults (3.0% versus 1.7%, respectively; p = 0.004). Being PSAC (adjusted Odds Ratio (aOR) = 0.2, p< 0.001; adjusted Infection Intensity Ratio (aIIR) = 0.1, p<0.001) or SAC (aOR = 0.5, p = 0.008; aIIR = 0.3, p = 0.01), being a female (aOR = 0.6, p = 0.004; aIIR = 0.3, p = 0.001), and having received deworming treatment the previous year (aOR = 0.4, p< 0.002; aIIR = 0.2, p<0.001) were associated with a lower prevalence and intensity of hookworm infection. Lower income (lowest quintile: aOR = 5.0, p<0.001, 2nd quintile aOR = 3.6, p = 0.001 and 3rd quintile aOR = 2.5, p = 0.02), being a farmer (aOR = 1.8, p = 0.02), medium population density (aOR = 2.6, p = 0.01), and open defecation (aOR = 0.5, p = 0.04) were associated with a higher prevalence of hookworm infection. Lower education-no education, primary or secondary school- (aIIR = 40.1, p = 0.01; aIIR = 30.9, p = 0.02; aIIR = 19.3, p = 0.04, respectively), farming (aIIR = 3.9, p = 0.002), natural flooring (aIIR = 0.2, p = 0.06), peri-urban settings (aIIR = 6.2, 95%CI 1.82-20.90, p = 0.003), and unimproved water source more than 30 minutes from the household (aIIR = 13.5, p = 0.02) were associated with a higher intensity of hookworm infection. Improved and unshared toilet was associated with lower intensity of hookworm infections (aIIR = 0.2, p = 0.01). SAC had a higher odds of Ascaris lumbricoides infection than adults (aOR = 2.0, p = 0.01) and females had a lower odds of infection (aOR = 0.5, p = 0.02). CONCLUSION: Hookworm spp. are the most prevalent STH in Comé, with a persistent reservoir in adults that is not addressed by current control measures based on school MDA. Expanding MDA to target adults and PSAC is necessary to substantially impact population prevalence, particularly for hookworm. TRIAL REGISTRATION: ClinicalTrials.gov NCT03014167.