Adapting strategies for effective and efficient pediatric HIV case finding in low prevalence countries: risk screening tool for testing children presenting at high-risk entry points in Ethiopia.

BACKGROUND: Implementing effective and efficient case-finding strategies is crucial to increasing pediatric antiretroviral therapy coverage. In Ethiopia, universal HIV testing is conducted for children presenting at high-risk entry points including malnutrition treatment, inpatient wards, tuberculosis (TB) clinics, index testing for children of positive adults, and referral of orphans and vulnerable children (OVC); however, low positivity rates observed at inpatient, malnutrition and OVC entry points warrant re-assessing current case-finding strategies. The aim of this study is to develop HIV risk screening tool applicable for testing children presenting at inpatient, malnutrition and OVC entry points in low-HIV prevalence settings. METHODS: The study was conducted from May 2017-March 2018 at 29 public health facilities in Amhara and Addis Ababa regions of Ethiopia. All children 2-14 years presenting to five high-risk entry points including malnutrition treatment, inpatient wards, tuberculosis (TB) clinics, index testing for children of positive adults, and referral of orphans and vulnerable children (OVC) were enrolled after consent. Data were collected from registers, medical records, and caregiver interviews. Screening tools were constructed using predictors of HIV positivity as screening items by applying both logistic regression and an unweighted method. Sensitivity, specificity and number needed to test (NNT) to identify one new child living with HIV (CLHIV) were estimated for each tool. RESULTS: The screening tools had similar sensitivity of 95%. However, the specificities of tools produced by logistic regression methods (61.4 and 65.6%) which are practically applicable were higher than those achieved by the unweighted method (53.6). Applying these tools could result in 58‒63% reduction in the NNT compared to universal testing approach while maintaining the overall number of CLHIV identified. CONCLUSION: The screening tools developed using logistic regression method could significantly improve HIV testing efficiency among children presenting to malnutrition, inpatient, and OVC entry points in Ethiopia while maintaining case identification. These tools are simplified to practically implement and can potentially be validated for use at various entry points. HIV programs in low-prevalence countries can also further investigate and optimize these tools in their settings.

Impact of an intensive facility-community case management intervention on 6-month HIV outcomes among select key and priority populations in Uganda.

INTRODUCTION: Key and priority populations (with risk behaviours and health inequities) are disproportionately affected by HIV in Uganda. We evaluated the impact of an intensive case management intervention on HIV treatment outcomes in Kalangala District, predominantly inhabited by fisher folk and female sex workers. METHODS: This quasi-experimental pre-post intervention evaluation included antiretroviral therapy naïve adults aged ≥ 18 years from six health facilities in the pre-intervention (Jan 1, 2017-December 31, 2017) and intervention phase (June 13, 2018-June 30, 2019). The primary outcomes were 6-month retention and viral suppression (VS) before and after implementation of the intervention involving facility and community case managers who supported participants through at least the first three months of ART. We used descriptive statistics to compared the characteristics, overall outcomes (i.e., retention, lost to follow up, died), and VS of participants by phase, and used mixed-effects logistic regression models to determine factors associated with 6-month retention in care. Marginal (averaging over facilities) probabilities of retention were computed from the final multivariable model. RESULTS: We enrolled 606 and 405 participants in the pre-intervention and intervention phases respectively. Approximately 75% of participants were aged 25-44 years, with similar age and gender distributions among phases. Approximately 46% of participants in the intervention were fisher folk and 9% were female sex workers. The adjusted probability of 6-month retention was higher in the intervention phase, 0.83 (95% CI: 0.77-0.90) versus pre-intervention phase, 0.73 (95% CI: 0.69-0.77, p = 0.03). The retention probability increased from 0.59 (0.49-0.68) to 0.73 (0.59-0.86), p = 0.03 among participants aged 18-24 years, and from 0.75 (0.71-0.78) to 0.85 (0.78-0.91), p = 0.03 among participants aged ≥ 25 years. VS (< 1,000 copies/mL) was approximately 87% in both phases. CONCLUSIONS: After implementation of the case management intervention, we observed significant improvement in 6-month retention in all age groups of a highly mobile population of predominantly fisher folk.

Impact of External Quality Assurance on the Quality of Xpert MTB/RIF Testing in Viet Nam.

Following the endorsement of the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) by the World Health Organization (WHO) in 2010, Viet Nam's National Tuberculosis Control Program (NTP) began using GeneXpert instruments in NTP laboratories. In 2013, Viet Nam's NTP implemented an Xpert MTB/RIF external quality assurance (EQA) program in collaboration with the U.S. Centers for Disease Control and Prevention (CDC) and the Foundation for Innovative New Diagnostics (FIND). Proficiency-testing (PT) panels comprising five dried tube specimens (DTS) were sent to participating sites approximately twice a year from October 2013 to July 2016. The number of enrolled laboratories increased from 22 to 39 during the study period. Testing accuracy was assessed by comparing reported and expected results; percentage scores were assigned; and feedback reports were provided to sites. On-site evaluation (OSE) was conducted for underperforming laboratories. The results from the first five rounds demonstrate the positive impact of PT and targeted OSE visits on testing quality. On average, for every additional round of feedback, the odds of achieving PT scores of ≥80% increased 2.04-fold (95% confidence interval, 1.39- to 3.00-fold). Future work will include scaling up PT to all sites and maintaining the performance of participating laboratories while developing local panel production capacity.

Prevalence and Correlates of Genital Infections Among Newly Diagnosed Human Immunodeficiency Virus-Infected Adults Entering Human Immunodeficiency Virus Care in Windhoek, Namibia.

BACKGROUND: Identifying and treating genital infections, including sexually transmitted infections (STI), among newly diagnosed human immunodeficiency virus (HIV)-infected individuals may benefit both public and individual health. We assessed prevalence of genital infections and their correlates among newly diagnosed HIV-infected individuals enrolling in HIV care services in Namibia. METHODS: Newly diagnosed HIV-infected adults entering HIV care at 2 health facilities in Windhoek, Namibia, were recruited from December 2012 to March 2014. Participants provided behavioral and clinical data including CD4+ T lymphocyte counts. Genital and blood specimens were tested for gonorrhea, Chlamydia, trichomoniasis, Mycoplasma genitalium, syphilis, bacterial vaginosis, and vulvovaginal candidiasis. RESULTS: Among 599 adults, 56% were women and 15% reported consistent use of condoms in the past 6 months. The most common infections were bacterial vaginosis (37.2%), trichomoniasis (34.6%) and Chlamydia (14.6%) in women and M. genitalium (11.4%) in men. Correlates for trichomoniasis included being female (adjusted relative risk, [aRR], 7.18; 95% confidence interval [CI], 4.07-12.65), higher education (aRR, 0.58; 95% CI, 0.38-0.89), and lower CD4 cell count (aRR, 1.61; 95% CI, 1.08-2.40). Being female (aRR, 2.39; 95% CI, 1.27-4.50), nonmarried (aRR, 2.30; (95% CI, 1.28-4.14), and having condomless sex (aRR, 2.72; 95% CI, 1.06-7.00) were independently associated with chlamydial infection. Across all infections, female (aRR, 2.31; 95% CI, 1.79-2.98), nonmarried participants (aRR, 1.29; 95% CI, 1.06-1.59), had higher risk to present with any STI, whereas pregnant women (aRR, 1.16, 95% CI 1.03-1.31) were at increased risk of any STI or reproductive tract infection.

Cervical Cancer Screening Positivity Among Women Living With HIV in CDC-PEPFAR Programs 2018-2022.

BACKGROUND: The US President's Emergency Plan for AIDS Relief aims to address the higher risk of cervical cancer among women living with HIV by offering high-quality screening services in the highest burden regions of the world. METHODS: We analyzed the US President's Emergency Plan for AIDS Relief Monitoring, Evaluation, and Reporting data from Centers for Disease Control and Prevention-supported sites in 13 countries in sub-Saharan Africa for women living with HIV aged older than 15 years who accessed cervical cancer screening services (mostly visual inspection, with ablative or excisional treatment offered for precancerous lesions), April 2018-March 2022. We calculated the positivity by age, country, and clinical visit type (first lifetime screen or routine rescreening). We fitted negative binomial random coefficient models of log-linear trends in time to estimate the probabilities of testing positive and any temporal trends in positivity. RESULTS: Among the 2.8 million completed cancer screens, 5.4% identified precancerous lesions, and 0.8% were positive for suspected invasive cervical cancers (6.1% overall). The positivity rates declined over the study period among those women screening for cervical cancer for the first time and among those women presenting to antiretroviral therapy clinics for routine rescreening. CONCLUSIONS: These positivity rates are lower than expectations set by the published literature. Further research is needed to determine whether these lower rates are attributable to the high level of consistent antiretroviral therapy use among these populations, and systematic program monitoring and quality assurance activities are essential to ensure women living with HIV have access to the highest possible quality prevention services.

Comparative performance of multiple-list estimators of key population size.

Estimates of the sizes of key populations (KPs) affected by HIV, including men who have sex with men, female sex workers and people who inject drugs, are required for targeting epidemic control efforts where they are most needed. Unfortunately, different estimators often produce discrepant results, and an objective basis for choice is lacking. This simulation study provides the first comparison of information-theoretic selection of loglinear models (LLM-AIC), Bayesian model averaging of loglinear models (LLM-BMA) and Bayesian nonparametric latent-class modeling (BLCM) for estimation of population size from multiple lists. Four hundred random samples from populations of size 1,000, 10,000 and 20,000, each including five encounter opportunities, were independently simulated using each of 30 data-generating models obtained from combinations of six patterns of variation in encounter probabilities and five expected per-list encounter probabilities, producing a total of 36,000 samples. Population size was estimated for each combination of sample and sequentially cumulative sets of 2-5 lists using LLM-AIC, LLM-BMA and BLCM. LLM-BMA and BLCM were quite robust and performed comparably in terms of root mean-squared error and bias, and outperformed LLM-AIC. All estimation methods produced uncertainty intervals which failed to achieve the nominal coverage, but LLM-BMA, as implemented in the dga R package produced the best balance of accuracy and interval coverage. The results also indicate that two-list estimation is unnecessarily vulnerable, and it is better to estimate the sizes of KPs based on at least three lists.

Population Size Estimation From Capture-Recapture Studies Using shinyrecap: Design and Implementation of a Web-Based Graphical User Interface.

BACKGROUND: Population size estimates (PSE) provide critical information in determining resource allocation for HIV services geared toward those at high risk of HIV, including female sex workers, men who have sex with men, and people who inject drugs. Capture-recapture (CRC) is often used to estimate the size of these often-hidden populations. Compared with the commonly used 2-source CRC, CRC relying on 3 (or more) samples (3S-CRC) can provide more robust PSE but involve far more complex statistical analysis. OBJECTIVE: This study aims to design and describe the Shiny application (shinyrecap), a user-friendly interface that can be used by field epidemiologists to produce PSE. METHODS: shinyrecap is built on the Shiny web application framework for R. This allows it to seamlessly integrate with the sophisticated CRC statistical packages (eg, Rcapture, dga, LCMCR). Additionally, the application may be accessed online or run locally on the user's machine. RESULTS: The application enables users to engage in sample size calculation based on a simulation framework. It assists in the proper formatting of collected data by providing a tool to convert commonly used formats to that used by the analysis software. A wide variety of methodologies are supported by the analysis tool, including log-linear, Bayesian model averaging, and Bayesian latent class models. For each methodology, diagnostics and model checking interfaces are provided. CONCLUSIONS: Through a use case, we demonstrated the broad utility of this powerful tool with 3S-CRC data to produce PSE for female sex workers in a subnational unit of a country in sub-Saharan Africa.

Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study.

BACKGROUND: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. METHODS: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. FINDINGS: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. INTERPRETATION: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. FUNDING: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.

Multilevel empirical bayes modeling for improved estimation of toxicant formulations to suppress parasitic sea lamprey in the upper great lakes.

Estimation of extreme quantal-response statistics, such as the concentration required to kill 99.9% of test subjects (LC99.9), remains a challenge in the presence of multiple covariates and complex study designs. Accurate and precise estimates of the LC99.9 for mixtures of toxicants are critical to ongoing control of a parasitic invasive species, the sea lamprey, in the Laurentian Great Lakes of North America. The toxicity of those chemicals is affected by local and temporal variations in water chemistry, which must be incorporated into the modeling. We develop multilevel empirical Bayes models for data from multiple laboratory studies. Our approach yields more accurate and precise estimation of the LC99.9 compared to alternative models considered. This study demonstrates that properly incorporating hierarchical structure in laboratory data yields better estimates of LC99.9 stream treatment values that are critical to larvae control in the field. In addition, out-of-sample prediction of the results of in situ tests reveals the presence of a latent seasonal effect not manifest in the laboratory studies, suggesting avenues for future study and illustrating the importance of dual consideration of both experimental and observational data.

Finding Children Living With HIV in Low-prevalence Countries: HIV Prevalence and Testing Yield From 5 Entry Points in Ethiopia.

BACKGROUND: Limited data in low HIV prevalence settings such as Ethiopia limit policy development and implementation of optimized pediatric testing approaches to close the treatment gap. This study aimed to determine HIV prevalence, testing yield and factors associated with HIV among children at 5 entry points. METHODS: We conducted a cross-sectional study from May 2017 to March 2018 in 29 public health facilities in Amhara and Addis Ababa regions in Ethiopia. Children 2-14 years were enrolled through 5 entry points. Data were obtained from registers, medical records and interviews with caregivers. HIV prevalence and testing yields were calculated for each entry point. Mixed-effects logistic regression analysis identified factors associated with undiagnosed HIV. RESULTS: The study enrolled 2166 children, of whom 94 were HIV positive (40 newly diagnosed). HIV prevalence and testing yield were the highest among children of HIV-positive adults (index testing; 8.2% and 8.2%, respectively) and children presenting to tuberculosis clinics (7.9% and 1.8%) or with severe malnutrition (6.5% and 1.4%). Factors associated with undiagnosed HIV included tuberculosis or index entry point [adjusted odds ratio (aOR), 11.97; 95% CI 5.06-28.36], deceased mother (aOR 4.55; 95% CI 1.30-15.92), recurrent skin problems (aOR 17.71; 95% CI 7.75-40.43), severe malnutrition (aOR 4.56; 95% CI 2.04-10.19) and urban residence (aOR 3.47; 95% CI 1.03-11.66). CONCLUSIONS: Index testing is a critical strategy for pediatric case finding in Ethiopia. Strategies and resources can prioritize minimizing missed opportunities in implementing universal testing for very sick children (tuberculosis, severe malnutrition) and implementing targeted testing in other entry points through use of factors associated with HIV.

Naomi: a new modelling tool for estimating HIV epidemic indicators at the district level in sub-Saharan Africa.

INTRODUCTION: HIV planning requires granular estimates for the number of people living with HIV (PLHIV), antiretroviral treatment (ART) coverage and unmet need, and new HIV infections by district, or equivalent subnational administrative level. We developed a Bayesian small-area estimation model, called Naomi, to estimate these quantities stratified by subnational administrative units, sex, and five-year age groups. METHODS: Small-area regressions for HIV prevalence, ART coverage and HIV incidence were jointly calibrated using subnational household survey data on all three indicators, routine antenatal service delivery data on HIV prevalence and ART coverage among pregnant women, and service delivery data on the number of PLHIV receiving ART. Incidence was modelled by district-level HIV prevalence and ART coverage. Model outputs of counts and rates for each indicator were aggregated to multiple geographic and demographic stratifications of interest. The model was estimated in an empirical Bayes framework, furnishing probabilistic uncertainty ranges for all output indicators. Example results were presented using data from Malawi during 2016-2018. RESULTS: Adult HIV prevalence in September 2018 ranged from 3.2% to 17.1% across Malawi's districts and was higher in southern districts and in metropolitan areas. ART coverage was more homogenous, ranging from 75% to 82%. The largest number of PLHIV was among ages 35 to 39 for both women and men, while the most untreated PLHIV were among ages 25 to 29 for women and 30 to 34 for men. Relative uncertainty was larger for the untreated PLHIV than the number on ART or total PLHIV. Among clients receiving ART at facilities in Lilongwe city, an estimated 71% (95% CI, 61% to 79%) resided in Lilongwe city, 20% (14% to 27%) in Lilongwe district outside the metropolis, and 9% (6% to 12%) in neighbouring Dowa district. Thirty-eight percent (26% to 50%) of Lilongwe rural residents and 39% (27% to 50%) of Dowa residents received treatment at facilities in Lilongwe city. CONCLUSIONS: The Naomi model synthesizes multiple subnational data sources to furnish estimates of key indicators for HIV programme planning, resource allocation, and target setting. Further model development to meet evolving HIV policy priorities and programme need should be accompanied by continued strengthening and understanding of routine health system data.

A global proficiency testing programme for Xpert® MTB/RIF using dried tube specimens, 2013-2015.

BACKGROUND: Proficiency testing (PT) is an important quality assurance measure toward ensuring accurate and reliable diagnostic test results from clinical and public health laboratories. Despite the rapid expansion of the Xpert® MTB/RIF assay for the detection of tuberculosis in resource-limited settings (RLS), low-cost PT materials for Xpert MTB/RIF external quality assessment (EQA) are not widely available. OBJECTIVE: We sought to determine whether a dried tube specimen (DTS)-based PT programme would be a feasible option to support Xpert MTB/RIF EQA in RLS. METHODS: Between 2013 and 2015, the United States Centers for Disease Control and Prevention developed and conducted a voluntary EQA programme using DTS-based PT material. Eight rounds of PT, each comprising five DTS samples, were provided to enrolled testing sites. After each round, participant results were compared to expected results, scored as satisfactory or unsatisfactory, and sites were provided with performance reports. RESULTS: Programme enrolment increased from 102 testing sites in seven countries to 441 testing sites in 14 countries over the course of three years. In each PT round, approximately 90% of participating sites demonstrated satisfactory performance. In seven of the 14 enrolled countries, the proportion of sites with a satisfactory score increased between the first round of participation and the most recent round of participation. CONCLUSION: This programme demonstrated that it is possible to implement an Xpert MTB/RIF PT programme for RLS using DTS, that substantial demand for Xpert MTB/RIF PT material exists in RLS, and that country performance can improve in a DTS-based PT programme.

Infant HIV diagnosis and turn-around time for testing in Malawi, 2015.

BACKGROUND: For HIV-exposed infants in Malawi, there are missed opportunities at each step of the testing and treatment cascade. OBJECTIVE: This study assessed factors associated with HIV positivity among infants in Malawi and turn-around times for infant HIV testing. METHODS: HIV testing data for infants aged 0-18 months from 2012 to 2015 were extracted from the Malawi HIV laboratory information management system and analysed using logistic regression. Turn-around time was defined as time between collection of samples to results dispatch from the laboratory. RESULTS: A total of 106 997 tests were included in the analyses. A subset of 76 006 observations with complete dates were included in the turn-around time analysis. Overall positivity was 4.2%. Factors associated with positivity were increasing age (infants aged 3-6 months: adjusted odds ratio [aOR] = 2.24; infants aged 6-9 months: aOR = 3.42; infants aged > 9 months: aOR = 4.24), female sex (aOR = 1.08) and whether the mother was alive and not on antiretroviral therapy at time of the infant's test (aOR = 1.57). Provision of HIV prophylaxis to the infant after birth (aOR = 0.38) was found to be protective against HIV positivity. The median turn-around time was 24 days (increased from 19 to 34 days between 2012 and 2015). CONCLUSION: Infant HIV positivity has decreased in Malawi, whereas turn-around time has increased. Factors associated with positivity include increasing age, female sex, and whether the mother was alive and not on antiretroviral therapy at the time of the infant's test.

Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi.

Background: Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin synthesis. In 2017, Malawian clinicians recognized a high incidence of pellagra-like rashes after scale-up of isoniazid preventive treatment (IPT) to people living with HIV (PLHIV). This increase in pellagra incidence among PLHIV coincided with a seasonal period of sustained food insecurity in the region, which obscured epidemiological interpretations. Although isoniazid has been implicated as a secondary cause of pellagra for decades, no hypothesis-driven epidemiological study has assessed this relationship in a population exposed to isoniazid. We developed this case-control protocol to assess the association between large-scale isoniazid distribution and pellagra in Malawi. Methods: We measure the relative odds of having pellagra among isoniazid-exposed people compared to those without exposure while controlling for other pellagra risk factors. Secondary aims include measuring time from isoniazid initiation to onset of dermatitis, comparing niacin metabolites 1-methylnicotinamide (1-MN), and l-methyl-2-pyridone-5-carboxamide (2-PYR) in urine as a proxy for total body niacin status among subpopulations, and describing clinical outcomes after 30-days multi-B vitamin (containing 300 mg nicotinamide daily) therapy and isoniazid cessation (if exposed). We aim to enroll 197 participants with pellagra and 788 age- and sex-matched controls (1:4 ratio) presenting at three dermatology clinics. Four randomly selected community clinics within 3-25 km of designated dermatology clinics will refer persons with pellagra-like symptoms to one of the study enrollment sites for diagnosis. Trained study dermatologists will conduct a detailed exposure questionnaire and perform anthropometric measurements. A subset of enrollees will provide a casual urine specimen for niacin metabolites quantification and/or point-of-care isoniazid detection to confirm whether participants recently ingested isoniazid. We will use conditional logistic regression, matching age and sex, to estimate odds ratios for the primary study aim. Discussion: The results of this study will inform the programmatic scale-up of isoniazid-containing regimens to prevent tuberculosis.

Improving estimates of district HIV prevalence and burden in South Africa using small area estimation techniques.

Many countries, including South Africa, have implemented population-based household surveys to estimate HIV prevalence and the burden of HIV infection. Most household HIV surveys are designed to provide reliable estimates down to only the first subnational geopolitical level which, in South Africa, is composed of nine provinces. However HIV prevalence estimates are needed down to at least the second subnational level in order to better target the delivery of HIV care, treatment and prevention services. The second subnational level in South Africa is composed of 52 districts. Achieving adequate precision at the second subnational level therefore requires either a substantial increase in survey sample size or use of model-based estimation capable of incorporating other pre-existing data. Our purpose is demonstration of the efficacy of relatively simple small-area estimation of HIV prevalence in the 52 districts of South Africa using data from the South African National HIV Prevalence, Incidence and Behavior Survey, 2012, district-level HIV prevalence estimates obtained from testing of pregnant women who attended antenatal care (ANC) clinics in 2012, and 2012 demographic data. The best-fitting model included only ANC prevalence and dependency ratio as out-of-survey predictors. Our key finding is that ANC prevalence was the superior auxiliary covariate, and provided substantially improved precision in many district-level estimates of HIV prevalence in the general population. Inclusion of a district-level spatial simultaneously autoregressive covariance structure did not result in improved estimation.

Novel Approaches for Estimating Female Sex Worker Population Size in Conflict-Affected South Sudan.

BACKGROUND: Limited data exist describing the population size of female sex workers (FSW) in South Sudan. A population size estimation exercise among FSW was undertaken in Juba and Nimule during the Eagle Survey. OBJECTIVE: The study aimed to estimate the number of FSW in Juba and Nimule to inform resource allocation and service provision for FSW. METHODS: We utilized service and unique object multipliers, and 3-source capture-recapture methods in conjunction with a respondent-driven sampling (RDS) survey to estimate the number of FSW in Juba and Nimule. For service multiplier, the number of FSW testing for HIV in 2015 (Juba) and 2016 (Nimule) was obtained from the LINKAGES program targeting FSW. Survey participants were asked whether they had been tested for HIV by LINKAGES during the relevant period. A total of 2 separate unique object distributions were conducted in Juba and Nimule. In Nimule, these were combined to produce a 3-source capture-recapture estimate. The exercise involved distribution of key chains and bangles to FSW, documentation of the number of those who received unique objects, and questions during RDS survey to assess whether participants received unique objects. RESULTS: In Juba, the service multiplier method yielded an estimate of 5800 (95% CI 4927-6673) FSW. The unique object estimate (key chain and RDS participation) yielded 5306 (95% CI 4673-5939). Another estimate using RDS participation and receipt of a bangle yielded a much lower estimate of 1863 (95% CI 1776-1951), as did a 2-source estimate of key chain and bangle (2120, 95% CI 2028-2211). A 3-source capture-recapture estimate could not be produced because aggregate rather than individual level data were collected during the third capture. The multiplier estimate using key chain and RDS participation was taken as the final population estimate for FSW in Juba, which constitutes more than 6% of the female population aged 15 to 64 years. In Nimule, the service multiplier method yielded an estimate of 9384 (95% CI 8511-10,257). The 2-source estimates for key chain and RDS yielded 6973 (95% CI 4759-9186); bangles and RDS yielded a higher estimate of 13,104 (95% CI 7101-19,106); key chains and bangles yielded a lower estimate of 1322 (95% CI 1223-1420). The 3-source capture-recapture method using Bayesian nonparametric latent-class model-based estimate yielded a population of 2694 (95% CI 1689-6945), and this was selected as the final estimate for Nimule, which constitutes nearly 40% of female population aged 15 to 64 years. CONCLUSIONS: The service and unique object multiplier, and 3-source capture-recapture methods were successfully used to estimate the number of FSW in Nimule, whereas service and unique object multiplier methods were successfully used in Juba. These methods yielded higher than previously estimated FSW population sizes. These estimates will inform resource allocation and advocacy efforts to support services for FSW.

Prediction of lethal/effective concentration/dose in the presence of multiple auxiliary covariates and components of variance.

Predictors of the percentile lethal/effective concentration/dose are commonly used measures of efficacy and toxicity. Typically such quantal-response predictors (e.g., the exposure required to kill 50% of some population) are estimated from simple bioassays wherein organisms are exposed to a gradient of several concentrations of a single agent. The toxicity of an agent may be influenced by auxiliary covariates, however, and more complicated experimental designs may introduce multiple variance components. Prediction methods lag examples of those cases. A conventional two-stage approach consists of multiple bivariate predictions of, say, medial lethal concentration followed by regression of those predictions on the auxiliary covariates. We propose a more effective and parsimonious class of generalized nonlinear mixed-effects models for prediction of lethal/effective dose/ concentration from auxiliary covariates. We demonstrate examples using data from a study regarding the effects of pH and additions of variable quantities 2',5'-dichloro-4'-nitrosalicylanilide (niclosamide) on the toxicity of 3-trifluoromethyl-4-nitrophenol to larval sea lamprey (Petromyzon marinus). The new models yielded unbiased predictions and root-mean-squared errors (RMSEs) of prediction for the exposure required to kill 50 and 99.9% of some population that were 29 to 82% smaller, respectively, than those from the conventional two-stage procedure. The model class is flexible and easily implemented using commonly available software.

Latent Tuberculosis Infection and Associated Factors among Health Care Workers in Kigali, Rwanda.

INTRODUCTION: Data are limited regarding tuberculosis (TB) and latent TB infection prevalence in Rwandan health facilities. METHODS: We conducted a cross-sectional survey among healthcare workers (HCWs) in Kigali during 2010. We purposively selected the public referral hospital, both district hospitals, and randomly selected 7 of 17 health centers. School workers (SWs) from the nearest willing public schools served as a local reference group. We tested for latent TB infection (LTBI) using tuberculin skin testing (TST) and asked about past TB disease. We assessed risk of LTBI and past history of TB disease associated with hospital employment. Among HCWs, we assessed risk associated with facility type (district hospital, referral hospital, health center), work setting (inpatient, outpatient), and occupation. RESULTS: Age, gender, and HIV status was similar between the enrolled 1,131 HCWs and 381 SWs. LTBI was more prevalent among HCWs (62%) than SWs (39%). Adjusted odds of a positive TST result were 2.71 (95% CI 2.01-3.67) times greater among HCWs than SWs. Among HCWs, there was no detectable difference between prevalence of LTBI according to facility type, work setting, or occupation. CONCLUSION: HCWs are at greater risk of LTBI, regardless of facility type, work setting, or occupation. The current status of TB infection control practices should be evaluated in the entire workforce in all Rwandan healthcare facilities.

Effects of methyl mercury exposure on the growth of juvenile common loons.

We conducted a dose-response laboratory study to quantify the level of mercury exposure associated with negative effects on the development of common loon chicks reared in captivity from hatch to 105 days. A dose regimen was implemented that provided exposure levels that bracketed relevant exposure levels of methyl mercury found in loon chicks across North America. We observed no overt signs of mercury toxicosis and detected no significant effect of dietary mercury exposure on growth or food consumption. However, asymptotic mass was lower in chicks that hatched from eggs collected from nests on low pH lakes relative to eggs from neutral pH lakes. Rapid excretion of methyl mercury during feather growth likely provides loon chicks protection from methyl mercury toxicity and may explain the lack of convincing toxicological findings in this study. Lake-source effects suggest that in ovo exposure to methyl mercury or other factors related to lake pH have consequences on chick development.