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Introduction We consider an analytical problem of characterising patterns and identifying discrepancies between database systems for longitudinal aggregated healthcare data involving multiple facilities.Methods We used routinely collected data on the registered number of people living with HIV who initiated antiretroviral treatment (ART) in 69 South African facilities in 2019; reported in the Three Interlinked Electronic register (Tier.net) and the District Health Information System. A Bayesian multiplicative interaction model quantified the average time effect as realised through the heterogeneous facility-specific slopes and quantified discrepancies between the two database sources.Results The estimated average trends showed a slight dip in June and a large dip in December. The estimated slopes identified clusters of facilities based on their ranges of fluctuations over time. The differences in average monthly ART initiations between the two database sources had a median of 1.6 (IQR 0.8–3.3), while 3 outlying facilities differed by at least 10 ART initiations between the 2 sources.Conclusion Multiplicative interaction models are a powerful tool for quantifying average trends over time and for evaluating discrepancies between reporting systems for multiple facilities with heterogeneous time slopes. The Bayesian framework enables efficient estimation for a very large number of parameters.

BackgroundThe World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing.Methods and findingsSixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB.ConclusionsOur trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence.Trial registrationSouth African National Clinical Trials Registry DOH-27-092021-4901.

[This corrects the article DOI: 10.1371/journal.pone.0230703.].

BackgroundYouth-led strategies remain untested in clinic-based programs to improve viral suppression (VS) and reduce stigma among HIV-positive adolescents and young adults (AYA) in sub-Saharan Africa. In response, Project YES! placed paid HIV-positive youth peer mentors (YPM) in four HIV clinics in Ndola, Zambia including a Children's Hospital (pediatric setting), an adult Hospital and two primary care facilities (adult settings).MethodsA randomized controlled trial was conducted from December 2017 to February 2019. Consecutively recruited 15 to 24-year-olds were randomly assigned to an intervention arm with monthly YPM one-on-one and group sessions and optional caregiver support groups, or a usual care comparison arm. Survey data and blood samples were collected at baseline and at the six-month midline. Generalized estimating equation models evaluated the effect of study arm over time on VS, antiretroviral treatment (ART) adherence gap, and internalized stigma.ResultsOut of 276 randomized youth, 273 were included in the analysis (Intervention n = 137, Comparison n = 136). VS significantly improved in both arms (I:63.5% to 73.0%; C:63.7% to 71.3.0%) [OR:1.49, 95% CI:1.08, 2.07]. In a stratified analysis intervention (I:37.5% to 70.5%) versus the comparison (C:60.3% to 59.4%) participants from the pediatric clinic experienced a relative increase in the odds of VS by a factor of 4.7 [interaction term OR:4.66, 95% CI:1.84, 11.78]. There was no evidence of a study arm difference in VS among AYA in adult clinics, or in ART adherence gaps across clinics. Internalized stigma significantly reduced by a factor of 0.39 [interaction term OR:0.39, 95% CI:0.21,0.73] in the intervention (50.4% to 25.4%) relative to the comparison arm (45.2% to 39.7%).ConclusionsProject YES! engaged AYA, improving VS in the pediatric clinic and internalized stigma in the pediatric and adult clinics. Further research is needed to understand the intersection of VS and internalized stigma among AYA attending adult HIV clinics.Trial registrationClinicalTrials.gov NCT04115813.

BackgroundThere is a dearth of comparative effectiveness research examining the implementation of different strategies for active tuberculosis (TB) case finding, particularly in rural settings, which represent 60% of the population of sub-Saharan Africa.Methods and findingsWe conducted a pragmatic, cluster-randomized comparative effectiveness trial of two TB case finding strategies (facility-based screening and contact tracing) in 56 public primary care clinics in two largely rural districts of Limpopo Province, South Africa. In the facility-based screening arm, sputum Xpert MTB/RIF was performed on all patients presenting (for any reason) with TB symptoms to 28 study clinics, and no contact tracing was performed. In the contact-tracing arm, contacts of patients with active TB were identified (via household tracing in 14 clinics and using small monetary incentives in the other 14 clinics), screened for TB symptoms, and offered Xpert MTB/RIF testing. The primary outcome was the number of newly identified patients with TB started on treatment. The analysis used multivariable Poisson regression adjusted for historical clinic-level TB case volumes and district. The trial was registered with ClinicalTrials.gov (NCT02808507). From July 18, 2017, to January 17, 2019, a total of 3,755 individuals started TB treatment across 56 study clinics in the 18-month period. Clinic characteristics and clinic-level averages of patient characteristics were similar across the two arms: 40/56 (71%) clinics were in a rural location, 2,136/3,655 (58%) patients were male, and 2,243 (61%) were HIV positive. The treatment initiation ratio comparing the yield of TB patients started on treatment in the facility-based arm compared to that from the contact-tracing arm was 1.04 (95% confidence interval [CI] 0.83-1.30, p = 0. 73). In the contact-tracing arm, 1,677 contacts of 788 new TB index patients were screened, yielding 12 new patients with TB. Prespecified subgroup analyses resulted in similar results, with estimated treatment initiation ratios of 0.96 (95% CI 0.64-1.27; p = 0.78) and 1.23 (95% CI 0.87-1.59; p = 0.29) among historically smaller and historically larger clinics, respectively. This ratio was 1.02 (95% CI 0.66-1.37; p = 0.93) and 1.08 (95% CI 0.74-1.42; p = 0.68) in the Vhembe and Waterberg districts, respectively. The estimated treatment initiation ratio was unchanged in sensitivity analyses excluding 24 records whose TB registration numbers could not be verified (1.03, 95% CI 0.82-1.29; p = 0.78) and excluding transfers-in (1.02, 95% CI 0.80-1.29; p = 0.71). Study limitations include the possibility of imbalance on cluster size owing to changes in catchment population over time and the inability to distinguish the independent effects of the two contact investigation strategies.ConclusionsContact tracing based on symptom screening and Xpert MTB/RIF testing did not increase the rate of treatment initiation for TB relative to the less resource-intensive approach of facility-based screening in this rural sub-Saharan setting.Trial registrationClinicalTrials.gov NCT02808507.

BACKGROUND:The 2015 earthquake in Nepal caused massive damages and triggered relief activities to minimize human suffering. The post-earthquake nutrition and food security situation in the hardest hit areas remains uncertain. METHODS:Two national cross-sectional surveys were conducted in 2014 and 2016 among households (HH) with pre-school aged children or newly married women. Of the 21 village development committees (VDCs) included in this sample, 7 fell within "earthquake-affected" areas. This paper presents data from 982 HH, 1015 women, and 883 children from 2014 and 1056 HH, 1083 women, and 998 children from 2016 living in these areas, with longitudinal overlap of about 55%. Prevalence estimates and 95% confidence intervals were calculated, and logistic regression was used to calculate p-values, both using robust estimates of standard errors to account for clustering. RESULTS:From 2014 to 2016, child wasting (weight-for-height z score

New human pathogens can emerge from the livestock-human interface and spread into human populations through many pathways including livestock products. Occupational contact with livestock is a risk factor for exposure to those pathogens and may cause further spreading of those pathogens in the community. The current study used whole genome sequencing to explore nasal Staphylococcus aureus obtained from hog slaughterhouse workers and their community members, all of whom resided in a livestock-dense region in rural North Carolina. Sequence data were analyzed for lineage distribution, pathogenicity-related genomic features, and mobile genetic elements. We observed evidence of nasal S. aureus differences between hog workers and non-workers. Nasal S. aureus from hog workers showed a greater lineage diversity than nasal S. aureus from community residents. Hog worker isolates were less likely to carry the φSa3 prophage and human-specific immune evasion cluster genes than community resident isolates (φSa3 prophage: 54.5% vs. 91.7%, Benjamini-Hochberg (BH) corrected p = 0.035; immune evasion cluster genes: 66.7% vs. 100%, BH p = 0.021). Hog worker isolates had a lower prevalence and diversity of enterotoxins than community resident isolates, particularly lacking the enterotoxin gene cluster (39.4% vs. 70.8%, BH p = 0.125). Moreover, hog worker isolates harbored more diverse antibiotic resistance genes, with a higher prevalence of carriage of multiple resistance genes, than community resident isolates (75.8% vs. 29.2%, BH p = 0.021). Phylogenetic analysis of all ST5 isolates, the most abundant lineage in the collection, further supported separation of isolates from hog workers and non-workers. Together, our observations suggest impact of occupational contact with livestock on nasal S. aureus colonization and highlight the need for further research on the complex epidemiology of S. aureus at the livestock-human interface.

Depression and depressive symptoms mediate the association between drug use and HIV risk. Yet, there are few interventions that target depressive symptoms and HIV risk for people who use drugs (PWUD). This study was a randomized controlled trial of an integrated cognitive behavioral therapy and HIV prevention intervention to reduce depressive symptoms, injection risk behaviors and increase condom use in a sample of urban people who used heroin or cocaine in the prior 6 months. A total of 315 individuals aged 18-55, who self-reported at least one HIV drug and sex risk behavior and scored ≥16 and

The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients.This study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity.Of the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4

Mortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB) and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA) result for urine lipoarabinomannan (LAM) and cryptococcal antigenuria was associated with mortality.351 hospitalized, HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospectively enrolled at Mulago National Referral Hospital in Uganda as part of a prospective accuracy evaluation of the lateral flow Determine TB LAM test. Stored frozen urine was retrospectively tested for cryptococcal antigen (CRAG) using the LFA. We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation.The median CD4 of the participants was 57 (IQR: 14-179) cells/µl and 41% (145) were microbiologically confirmed TB cases. LAM LFA was positive in 38% (134), 7% (25) were CRAG positive, and 43% (151) were positive for either test in urine. Overall, 21% (75) died within the first 2 months, and a total of 32% (114) were confirmed dead by 6 months. At 2 months, 30% of LAM or CRAG positive patients were confirmed dead compared to 15.0% of those who were negative. In an adjusted model, LAM or CRAG positive results were associated with an increased risk of death (RRR 2.29, 95% CI: 1.29, 4.05; P = 0.005).In hospitalized HIV-infected patients, LAM or CRAG LFA positivity was associated with subsequent death within 2 months. Further studies are warranted to examine the impact of POC diagnostic 'test and treat' approach on patient-centered outcomes.

Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults.Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

BACKGROUND:Rapid and cost-effective methods for HIV-1 diagnosis and viral load monitoring would greatly enhance the clinical management of HIV-1 infected adults and children in limited-resource settings. Recent recommendations to treat perinatally infected infants within the first year of life are feasible only if early diagnosis is routinely available. Dried blood spots (DBS) on filter paper are an easy and convenient way to collect and transport blood samples. A rapid and cost effective method to diagnose and quantify HIV-1 from DBS is urgently needed to facilitate early diagnosis of HIV-1 infection and monitoring of antiretroviral therapy. METHODS AND FINDINGS:We have developed a real-time LightCycler (rtLC) PCR assay to detect and quantify HIV-1 from DBS. HIV-1 RNA extracted from DBS was amplified in a one-step, single-tube system using primers specific for long-terminal repeat sequences that are conserved across all HIV-1 clades. SYBR Green dye was used to quantify PCR amplicons and HIV-1 RNA copy numbers were determined from a standard curve generated using serially diluted known copies of HIV-1 RNA. This assay detected samples across clades, has a dynamic range of 5 log(10), and %CV

Abstract Background Intimate partner violence (IPV), HIV and sexually transmitted infections (STI) can contribute to disparities in population health, depending on the individual, social and environmental factors characterizing a setting. To better understand the place-based determinants and patterns of these key interrelated public health problems in Uganda, we compared risk factors for IPV, HIV and STI in fishing, trading and agrarian communities in Rakai, Uganda by gender. Method This study used cross-sectional data collected from 14,464 sexually active men (n = 6531) and women (n = 7933) as part of the Rakai Community Cohort Study, a population-based open cohort study of men and women aged 15–49 years. We used multilevel modified poisson regression models, which incorporated random intercepts for community and households. Factors associated with IPV, HIV and STI were assessed separately for men and women in fishing, trading and agrarian communities. Results A larger proportion of participants in the fishing communities than those in trading and agrarian communities were HIV positive, engaged in HIV risk behaviors, had STI symptoms and reported perpetration of or victimization by IPV. Female gender was a shared correlate of IPV, HIV and STI in the fishing communities. Engagement in multiple sexual relationships or partner’s engagement in multiple relationships were shared correlates of IPV, and HIV in agrarian communities and IPV and STI in trading communities. Conclusion Programs should target factors at multiple levels to reduce risk for syndemic conditions of HIV, STI and IPV in Rakai, Uganda particularly among men and women in fishing communities.

Abstract Background Studies have revealed associations between preceding short and long birth-to-birth or birth-to-pregnancy intervals and poor pregnancy outcomes. Most of these studies, however, have examined the effect of intervals that began with live births. Using data from Bangladesh, we examined the effect of inter-outcome intervals (IOI) starting with a non-live birth or neonatal death, on outcomes in the next pregnancy. Pregnancy spacing behaviors in rural northeast Bangladesh have changed little since 2004. Methods We analyzed pregnancy histories for married women aged 15-49 years who had outcomes between 2000 and 2006 in Sylhet, Bangladesh. We examined the effects of the preceding outcome and the IOI length on the risk of stillbirth, neonatal death and spontaneous abortion using multinomial logistic regression models. Results Data included 64,897 pregnancy outcomes from 33,495 mothers. Inter-outcome intervals of 27-50 months and live births were baseline comparators. Stillbirths followed by IOI’s

We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.