Distinct cytokine profiles in late pregnancy in Ugandan people with HIV.

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α -KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

COVID-19 vaccination strategies in Africa: A scoping review of the use of mathematical models to inform policy.

OBJECTIVE: Mathematical models are vital tools to understand transmission dynamics and assess the impact of interventions to mitigate COVID-19. However, historically, their use in Africa has been limited. In this scoping review, we assess how mathematical models were used to study COVID-19 vaccination to potentially inform pandemic planning and response in Africa. METHODS: We searched six electronic databases: MEDLINE, Embase, Web of Science, Global Health, MathSciNet and Africa-Wide NiPAD, using keywords to identify articles focused on the use of mathematical modelling studies of COVID-19 vaccination in Africa that were published as of October 2022. We extracted the details on the country, author affiliation, characteristics of models, policy intent and heterogeneity factors. We assessed quality using 21-point scale criteria on model characteristics and content of the studies. RESULTS: The literature search yielded 462 articles, of which 32 were included based on the eligibility criteria. Nineteen (59%) studies had a first author affiliated with an African country. Of the 32 included studies, 30 (94%) were compartmental models. By country, most studies were about or included South Africa (n = 12, 37%), followed by Morocco (n = 6, 19%) and Ethiopia (n = 5, 16%). Most studies (n = 19, 59%) assessed the impact of increasing vaccination coverage on COVID-19 burden. Half (n = 16, 50%) had policy intent: prioritising or selecting interventions, pandemic planning and response, vaccine distribution and optimisation strategies and understanding transmission dynamics of COVID-19. Fourteen studies (44%) were of medium quality and eight (25%) were of high quality. CONCLUSIONS: While decision-makers could draw vital insights from the evidence generated from mathematical modelling to inform policy, we found that there was limited use of such models exploring vaccination impacts for COVID-19 in Africa. The disparity can be addressed by scaling up mathematical modelling training, increasing collaborative opportunities between modellers and policymakers, and increasing access to funding.

Increasing access to pediatric surgical care: Assessing district hospital readiness in rural Rwanda.

Introduction/Background: Safe and quality surgery is crucial for child health. In Rwanda, district hospitals serve as primary entry points for pediatric patients needing surgical care. This paper reports on the organizational readiness and facility capacity to provide pediatric surgery in three district hospitals in rural Rwanda. Methods: We administered the Children's Surgical Assessment Tool (CSAT), adapted for a Rwandan district hospital, to assess facility readiness across 5 domains (infrastructure, workforce, service delivery, financing, and training) at three Partners in Health supported district hospitals (Kirehe, Rwinkwavu, and Butaro District Hospitals). We used the Safe Surgery Organizational Readiness Tool (SSORT) to measure perceived individual and team readiness to implement surgical quality improvement interventions across 14 domains. Results: None of the facilities had a dedicated pediatric surgeon, and the most common barriers to pediatric surgery were lack of surgeon (68%), lack of physician anesthesiologists (19%), and inadequate infrastructure (17%). There were gaps in operating and recovery room infrastructure, and information management for pediatric outpatients and referrals. In SSORT interviews (n=47), the highest barriers to increasing pediatric surgery capacity were facility capacity (mean score=2.6 out of 5), psychological safety (median score=3.0 out of 5), and resistance to change (mean score=1.5 out of 5 with 5=no resistance). Conclusions: This study highlights challenges in providing safe and high-quality surgical care to pediatric patients in three rural district hospitals in Rwanda. It underscores the need for targeted interventions to address facility and organizational barriers prior to implementing interventions to expand pediatric surgical capacity.

Evidence-based Decision Making: Infectious Disease Modeling Training for Policymakers in East Africa.

Background: Mathematical modeling of infectious diseases is an important decision-making tool for outbreak control. However, in Africa, limited expertise reduces the use and impact of these tools on policy. Therefore, there is a need to build capacity in Africa for the use of mathematical modeling to inform policy. Here we describe our experience implementing a mathematical modeling training program for public health professionals in East Africa. Methods: We used a deliverable-driven and learning-by-doing model to introduce trainees to the mathematical modeling of infectious diseases. The training comprised two two-week in-person sessions and a practicum where trainees received intensive mentorship. Trainees evaluated the content and structure of the course at the end of each week, and this feedback informed the strategy for subsequent weeks. Findings: Out of 875 applications from 38 countries, we selected ten trainees from three countries - Rwanda (6), Kenya (2), and Uganda (2) - with guidance from an advisory committee. Nine trainees were based at government institutions and one at an academic organization. Participants gained skills in developing models to answer questions of interest and critically appraising modeling studies. At the end of the training, trainees prepared policy briefs summarizing their modeling study findings. These were presented at a dissemination event to policymakers, researchers, and program managers. All trainees indicated they would recommend the course to colleagues and rated the quality of the training with a median score of 9/10. Conclusions: Mathematical modeling training programs for public health professionals in Africa can be an effective tool for research capacity building and policy support to mitigate infectious disease burden and forecast resources. Overall, the course was successful, owing to a combination of factors, including institutional support, trainees' commitment, intensive mentorship, a diverse trainee pool, and regular evaluations.

Are populations of postpartum women differentially served by community health worker programs: an observational cohort study from Zanzibar, Tanzania.

BACKGROUND: Although community health worker (CHW) programs focus on improving access to healthcare, some individuals may not receive the intended quality or quantity of an intervention. The objective of this research was to examine if certain populations of pregnant women differentially experience the implementation of a community health worker-led maternal health intervention in Zanzibar. METHODS: We included pregnant women enrolled in the Safer Deliveries (Uzazi Salama) program, which operated in 10 of 11 districts in Zanzibar, Tanzania between January 1, 2017, and June 19, 2019 (N = 33,914). The outcomes of interest were receipt of the entire postpartum intervention (three CHW visits) and time to first postpartum CHW visit (days). Visits by CHWs were done at the women's home, however, a telehealth option existed for women who were unable to be reached in-person. We conducted statistical tests to investigate the bivariate associations between our outcomes and each demographic and health characteristic. We used multivariate logistic regression to estimate the relationships between covariates and the outcomes and multivariate linear regression to estimate the association between covariates and the average time until first postpartum visit. RESULTS: Higher parity (OR = 0.85; P = 0.014; 95%CI: 0.75-0.97), unknown or unreported HIV status (OR = 0.64; p < 0.001; 95%CI: 0.53-0.78), and receipt of phone consultations (OR = 0.77; p < 0.001; 95%CI: 0.69-0.87) were associated with a lower odds of receiving all postpartum visits. Similarly, women with an unknown or unreported HIV status (estimated mean difference of 1.81 days; p < 0.001; 95%CI: 1.03-2.59) and those who received a phone consultation (estimated mean difference of 0.83 days; p < 0.001; 95%CI: 0.43-1.23), on average, experienced delays to first visit. In addition, current delivery at a referral hospital was associated with lower odds of receiving a postpartum visit and longer time to first visit compared to delivery at home, cottage hospital, PHCU + , or district hospital. Women from all other districts received their first visit earlier than women from Kaskazini B. There were no differences in the odds of receiving the entire postpartum intervention by sociodemographic variables, including age, education, and poverty assessment indicators. CONCLUSION: The results indicate no differences in intervention contact across wealth and education levels, suggesting that the program is effectively reaching women regardless of SES. However, women with other characteristics (e.g., higher parity, unknown or unreported HIV status) had lower odds of receiving the complete intervention. Overall, this work generates knowledge on existing disparities in intervention coverage and enables future programs to develop approaches to achieve equity in health care utilization and outcomes.

Regional variation in weight change after the transition to dolutegravir: a prospective cohort study in Uganda and South Africa.

BACKGROUND: People with HIV (PWH) on integrase inhibitor-based regimens may be at risk of excess weight gain, but it is unclear if this risk is consistent across settings. We assessed weight change over 48 weeks among PWH who were transitioned to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD). DESIGN: We conducted a prospective cohort study at public-sector HIV clinics in Uganda and South Africa. METHODS: Eligible participants were adults who were transitioned to TLD. Weight was measured at enrollment, 24-, and 48-weeks post TLD transition. Our outcomes were (1) weight change, (2) change in waist circumference, and (3) clinically significant weight gain, defined as ≥10% increase in weight from baseline, over 48 weeks. We used linear mixed-effects regression models, adjusted for demographic factors, to estimate weight gain and identify risk factors. RESULTS: Weight data were available for 428 participants in Uganda and 367 in South Africa. The mean weight change was 0.6 kg [95%CI: 0.1-1.0] in Uganda and 2.9 kg [2.3-3.4] in South Africa (p < 0.001). The mean change in waist circumference was 0.8 cm [95%CI: 0.0-1.5]) in Uganda and 2.3 cm [95%CI: 1.4-3.2] in South Africa (p = 0.012). Clinically significant weight gain occurred in 9.8% [7.0-12.6] of participants in Uganda and 18.0% [14.1-21.9] in South Africa (p < 0.001). After adjustment, PWH gained significantly less weight in Uganda than in South Africa. CONCLUSIONS: PWH in South Africa experienced significantly greater weight gain and increases in waist circumference compared to Uganda. Strategies to address weight gain in PWH should be carefully considered and may vary by region.

Adaptation and validation of the Children's Surgical Assessment Tool for Rwandan district hospitals.

BACKGROUND/AIMS: Paediatric surgical care is a critical component of child health and basic universal health coverage and therefore should be included in comprehensive evaluations of surgical capacity. This study adapted and validated the Children's Surgical Assessment Tool (CSAT), a tool developed for district and tertiary hospitals in Nigeria to evaluate hospital infrastructure, workforce, service delivery, financing, and training capacity for paediatric surgery, for use in district hospitals in Rwanda. METHODS: We used a three-round modified Delphi process to adapt the CSAT to the Rwandan context. An expert panel of surgeons, anaesthesiologists, paediatricians, and health systems strengthening experts were invited to participate based on their experience with paediatric surgical or anaesthetic care at district hospitals or with health systems strengthening in the Rwandan context. We used the Content Validity Index to validate the final tool. RESULTS: The adapted tool had a final score of 0.84 on the Content Validity Index, indicating a high level of agreement among the expert panel. The final tool comprised 171 items across five domains: facility characteristics, service delivery, workforce, financing, and training/research. CONCLUSION: The adapted CSAT is appropriate for use in district hospitals in Rwanda to evaluate the capacity for paediatric surgery. This study provides a framework for adapting and validating a comprehensive paediatric surgical assessment tool to local contexts in LMICs and used in similar settings in sub-Saharan Africa.

Functional recovery after cesarean delivery: a prospective cohort study in rural Rwanda.

INTRODUCTION: Women who deliver via cesarean section (c-section) experience short- and long-term disability that may affect their physical health and their ability to function normally. While clinical complications are assessed, postpartum functional outcomes are not well understood from a patient's perspective or well-characterized by previous studies. In Rwanda, 11% of rural women deliver via c-section. This study explores the functional recovery of rural Rwandan women after c-section and assesses factors that predict poor functionality at postoperative day (POD) 30. METHODS: Data were collected prospectively on POD 3, 11, and 30 from women delivering at Kirehe District Hospital between October 2019 and March 2020. Functionality was measured by self-reported overall health, energy level, mobility, self-care ability, and ability to perform usual activities; and each domain was rated on a 4-point likert scale, lower scores reflecting higher level of difficulties. Using the four functionality domains, we computed composite mean scores with a maximum score of 4.0 and we defined poor functionality as composite score of ≤ 2.0. We assessed functionality with descriptive statistics and logistic regression. RESULTS: Of 617 patients, 54.0%, 25.9%, and 26.8% reported poor functional status at POD3, POD11, and POD30, respectively. At POD30, the most self-reported poor functionality dimensions were poor or very poor overall health (48.1%), and inability to perform usual activities (15.6%). In the adjusted model, women whose surgery lasted 30-45 min had higher odds of poor functionality (aOR = 1.85, p = 0.01), as did women who experienced intraoperative complications (aOR = 4.12, 95% CI (1.09, 25.57), p = 0.037). High income patients had incrementally lower significant odds of poor physical functionality (aOR = 0.62 for every US$1 increase in monthly income, 95% CI (0.40, 0.96) p = 0.04). CONCLUSION: We found a high proportion of poor physical functionality 30 days post-c-section in this Rwandan cohort. Surgery lasting > 30 min and intra-operative complications were associated with poor functionality, whereas a reported higher income status was associated with lower odds of poor functionality. Functional status assessments, monitoring and support should be included in post-partum care for women who delivered via c-section. Effective risk mitigating intervention should be implemented to recover functionality after c-section, particularly among low-income women and those undergoing longer surgical procedures or those with intraoperative complications.

Long travel times from health center to hospital reduce caesarean section access: a study from Kirehe District, Rwanda.

Introduction: timely access to safe cesarean section (c-section) delivery can save the lives of mothers and neonates. This paper explores how distance affects c-section access in rural sub-Saharan Africa, where women in labor present to health centers before being referred to district hospitals for surgical care. Methods: this study included all adult women delivering via c-section between April 2017 and March 2018 in Kirehe District, Rwanda. We assessed the association between travel times and village-level c-section rates. Results: the estimated travel time from home-to-health center was 26 minutes (IQR: 13, 41) and from health center-to-hospital was 43 minutes (IQR: 2, 59). There was no significant association between travel time from home-to-health center and c-section rates (RR=1.01, p=0.42), but the association was significant for health center-to-hospital travel times (RR=0.96, p=0.01); for every 15-minute increase in travel time, there was a 4% decrease in c-sections for a health center catchment area. Conclusion: in the context of decentralized health services, minimizing health center to hospital referral barriers is of utmost importance for improving c-section access in rural sub-Saharan Africa.

Late and Persistent Symptoms Suggestive of Surgical Site Infections After Cesarean Section: Results from a Prospective Cohort Study in Rural Rwanda.

Background: Women in low-resource settings will likely develop late surgical site infections (SSIs), diagnosed after post-operative day (POD) 10. We measured SSI prevalence and predictors of late and persistent SSIs-suggestive symptoms among women who delivered via cesarean section (c-section). Patients and Methods: Women who underwent c-sections at Kirehe District Hospital (KDH) between September 2019 and February 2020 were prospectively enrolled. Data were collected on POD1, POD11, and POD30. Logistic regression identified factors associated with persistent and late SSI symptoms. Results: In total, 808 women were study enrolled. Of these, 646 women physically attended the POD11 clinic visit follow-up, while 671 received the POD30 telephone-based follow-up review. Thirty-three (5.0%) women were diagnosed with an SSI on POD11, and 39 (5.3%) had an SSI diagnosis during POD11 to POD30, giving a cumulative prevalence of 10.3% late SSI rate. Of 671, 400 (59.9%) reported at least one SSI-associated symptom between POD11 and POD30. The reported symptoms included pain (56.6%), fever (19.4%), or incision drainage (16.6%). Of these, 200 women reported still having at least one of these symptoms on POD30. Of the 400 women with late SSI symptoms, 232 (58.0%) did not seek care, and of these, 80 (48.5%), 59 (35.8%), and 15 (8.9%) could not afford transport fare, did not believe symptoms were severe for a medical visit, and were not able to travel, respectively. Lower odds of late SSI-suggestive symptoms were reported among women with health insurance (adjusted odds ratio [aOR], 0.06; p = 0.013), whereas higher late SSI-suggestive symptoms odds were among women with wealthier socioeconomic status (aOR, 2.88; p = 0.004). Conclusions: Women in rural Rwanda are at risk of late and persistent SSI-suggestive symptoms. Financial barriers and the perception that their symptoms were not serious enough for the medical visit need education on early care seeking and interventions to mitigate financial barriers for optimizing perinatal care.

Area-Based Sociodemographic Factors Associated with Latent Tuberculosis Infection in a Low-Prevalence Setting.

Area-based sociodemographic markers, such as census tract foreign-born population, have been used to identify individuals and communities with a high risk for tuberculosis (TB) infection in the United States. However, these markers have not been evaluated as independent risk factors for TB infection in children. We evaluated associations between census tract poverty, crowding, foreign-born population, and the CDC's Social Vulnerability Index (CDC-SVI) ranking and TB infection in a population of children tested for TB infection in Boston, Massachusetts. After adjustment for age, crowding, and foreign-born percentage, increasing census tract poverty was associated with increased odds of TB infection (adjusted odds ratio [aOR] per 10% increase in population proportion living in poverty: 1.20 [95% CI, 1.04-1.40]; P = 0.01), although this association was attenuated after further adjustment for preferred language. In separate models, increasing CDC-SVI ranking was associated with increased odds of TB infection, including after adjustment for age and language preference (aOR per 10-point increase in CDC-SVI rank: 1.08 [95% CI, 1.02-1.15]; P = 0.01). Our findings suggest area-based sociodemographic factors may be valuable for characterizing TB infection risk and defining the social ecology of pediatric TB infection in low-burden settings.

COVID-19 vaccine acceptance in three rural communes in Haiti: A cross-sectional study.

Vaccines are the most effective mechanism for ending the COVID-19 pandemic. However, reluctance to accept vaccines has hindered the efforts of health authorities to combat the virus. In Haiti, as of July 2021, less than 1% of the country's population has been fully vaccinated in part due to vaccine hesitancy. Our goal was to assess Haitian attitudes toward COVID-19 vaccination and investigate the primary reasons for Moderna vaccine hesitancy. We conducted a cross-sectional survey across three rural Haitian communities, in September 2021. The research team used electronic tablets to collect quantitative data from 1,071 respondents, selected randomly across the communities. We report descriptive statistics and identify variables associated with vaccine acceptance using logistic regression built using a backward stepwise approach. Among 1,071 respondents, the overall acceptance rate was 27.0% (n = 285). The most common reason for vaccine hesitancy was "concern about side effects" (n = 484, 67.1%) followed by "concern about contracting COVID-19 from the vaccine" (n = 472, 65.4%). Three-quarters of respondents (n = 817) identified their healthcare workers as their most trustworthy source for information related to the vaccine. In the bivariate analysis, male gender (p = .06) and no history of drinking alcohol (p < .001) were significantly associated with being more likely to take the vaccine. In the final reduced model, only those with a history of drinking alcohol were significantly more likely to take the vaccine (aOR = 1.47 (1.23, 1.87) p < .001). The acceptance rate for the COVID-19 vaccine is low, and public health experts should design and strengthen vaccination campaigns to combat misinformation and public distrust.

Predicting facility-based delivery in Zanzibar: The vulnerability of machine learning algorithms to adversarial attacks.

Background: Community health worker (CHW)-led maternal health programs have contributed to increased facility-based deliveries and decreased maternal mortality in sub-Saharan Africa. The recent adoption of mobile devices in these programs provides an opportunity for real-time implementation of machine learning predictive models to identify women most at risk for home-based delivery. However, it is possible that falsified data could be entered into the model to get a specific prediction result - known as an "adversarial attack". The goal of this paper is to evaluate the algorithm's vulnerability to adversarial attacks. Methods: The dataset used in this research is from the Uzazi Salama ("Safer Deliveries") program, which operated between 2016 and 2019 in Zanzibar. We used LASSO regularized logistic regression to develop the prediction model. We used "One-At-a-Time (OAT)" adversarial attacks across four different types of input variables: binary - access to electricity at home, categorical - previous delivery location, ordinal - educational level, and continuous - gestational age. We evaluated the percent of predicted classifications that change due to these adversarial attacks. Results: Manipulating input variables affected prediction results. The variable with the greatest vulnerability was previous delivery location, with 55.65% of predicted classifications changing when applying adversarial attacks from previously delivered at a facility to previously delivered at home, and 37.63% of predicted classifications changing when applying adversarial attacks from previously delivered at home to previously delivered at a facility. Conclusion: This paper investigates the vulnerability of an algorithm to predict facility-based delivery when facing adversarial attacks. By understanding the effect of adversarial attacks, programs can implement data monitoring strategies to assess for and deter these manipulations. Ensuring fidelity in algorithm deployment secures that CHWs target those women who are actually at high risk of delivering at home.

Oxygen saturation targets for adults with acute hypoxemia in low and lower-middle income countries: a scoping review with analysis of contextual factors.

Knowing the target oxygen saturation (SpO2) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO2 targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances. For this literature review and analysis, we considered SpO2 targets used in previous trials, international and national society guidelines, and direct trial evidence comparing outcomes using different SpO2 ranges (all from HICs). We also considered contextual factors, including emerging data on pulse oximetry performance in different skin pigmentation ranges, the risk of depleting oxygen resources in LMIC settings, the lack of access to arterial blood gases that necessitates consideration of the subpopulation of hypoxemic patients who are also hypercapnic, and the impact of altitude on median SpO2 values. This process of integrating prior study protocols, society guidelines, available evidence, and contextual factors is potentially useful for the development of other clinical guidelines for LMIC settings. We suggest that a goal SpO2 range of 90-94% is reasonable, using high-performing pulse oximeters. Answering context-specific research questions, such as an optimal SpO2 target range in LMIC contexts, is critical for advancing equity in clinical outcomes globally.

The impact of COVID-19 and national pandemic responses on health service utilisation in seven low- and middle-income countries.

BACKGROUND: The COVID-19 pandemic has disrupted health services worldwide, which may have led to increased mortality and secondary disease outbreaks. Disruptions vary by patient population, geographic area, and service. While many reasons have been put forward to explain disruptions, few studies have empirically investigated their causes. OBJECTIVE: We quantify disruptions to outpatient services, facility-based deliveries, and family planning in seven low- and middle-income countries during the COVID-19 pandemic and quantify relationships between disruptions and the intensity of national pandemic responses. METHODS: We leveraged routine data from 104 Partners In Health-supported facilities from January 2016 to December 2021. We first quantified COVID-19-related disruptions in each country by month using negative binomial time series models. We then modelled the relationship between disruptions and the intensity of national pandemic responses, as measured by the stringency index from the Oxford COVID-19 Government Response Tracker. RESULTS: For all the studied countries, we observed at least one month with a significant decline in outpatient visits during the COVID-19 pandemic. We also observed significant cumulative drops in outpatient visits across all months in Lesotho, Liberia, Malawi, Rwanda, and Sierra Leone. A significant cumulative decrease in facility-based deliveries was observed in Haiti, Lesotho, Mexico, and Sierra Leone. No country had significant cumulative drops in family planning visits. For a 10-unit increase in the average monthly stringency index, the proportion deviation in monthly facility outpatient visits compared to expected fell by 3.9% (95% CI: -5.1%, -1.6%). No relationship between stringency of pandemic responses and utilisation was observed for facility-based deliveries or family planning. CONCLUSIONS: Context-specific strategies show the ability of health systems to sustain essential health services during the pandemic. The link between pandemic responses and healthcare utilisation can inform purposeful strategies to ensure communities have access to care and provide lessons for promoting the utilisation of health services elsewhere.

The Cascade of Care for Hepatitis C Treatment in Rwanda: A Retrospective Cohort Study of the 2017-2019 Mass Screening and Treatment Campaign.

Access to hepatitis C (HCV) testing and treatment is still limited globally. To address this, the Government of Rwanda launched a voluntary mass screening and treatment campaign in 2017. We studied the progression of patients through the cascade of HCV care during this campaign. We conducted a retrospective cohort study and included all patients screened at 46 hospitals between April 2017 and October 2019. We used hierarchical logistic regression to assess factors associated with HCV positivity, gaps in care, and treatment failure. A total of 860,801 people attended the mass screening during the study period. Some 5.7% tested positive for anti-HCV, and 2.9% were confirmed positive. Of those who were confirmed positive, 52% initiated treatment, and 72% of those initiated treatment, completed treatment and returned for assessment 12 weeks afterward. The cure rate was 88%. HCV positivity was associated with age, socio-economic status, sex, marital status, and HIV coinfection. Treatment failure was associated with cirrhosis, baseline viral load, and a family history of HCV. Our results suggest that future HCV screening and testing interventions in Rwanda and other similar settings should target high-risk groups. High dropout rates suggest that more effort should be put into patient follow-up to increase adherence to care.

Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure.

OBJECTIVE: We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART). DESIGN: We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa. METHODS: Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen. RESULTS: Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% ( n = 243/283). Of those with TFV detected on the POC assay, 91% ( n  = 204/224) had HIVDR, vs. only 66% ( n  = 39/59) among those with no TFV detected ( P- value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively. CONCLUSIONS: In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.

Practical strategies for operationalizing optimal allocation in stratified cluster-based outcome-dependent sampling designs.

Cluster-based outcome-dependent sampling (ODS) has the potential to yield efficiency gains when the outcome of interest is relatively rare, and resource constraints allow only a certain number of clusters to be visited for data collection. Previous research has shown that when the intended analysis is inverse-probability weighted generalized estimating equations, and the number of clusters that can be sampled is fixed, optimal allocation of the (cluster-level) sample size across strata defined by auxiliary variables readily available at the design stage has the potential to increase efficiency in the estimation of the parameter(s) of interest. In such a setting, the optimal allocation formulae depend on quantities that are unknown in practice, currently making such designs difficult to implement. In this paper, we consider a two-wave adaptive sampling approach, in which data is collected from a first wave sample, and subsequently used to compute the optimal second wave stratum-specific sample sizes. We consider two strategies for estimating the necessary components using the first wave data: an inverse-probability weighting (IPW) approach and a multiple imputation (MI) approach. In a comprehensive simulation study, we show that the adaptive sampling approach performs well, and that the MI approach yields designs that are very near-optimal, regardless of the covariate type. The IPW approach, on the other hand, has mixed results. Finally, we illustrate the proposed adaptive sampling procedures with data on maternal characteristics and birth outcomes among women enrolled in the Safer Deliveries program in Zanzibar, Tanzania.

Multicenter Analysis of Attrition from the Pediatric Tuberculosis Infection Care Cascade in Boston.

OBJECTIVE: To characterize losses from the pediatric tuberculosis (TB) infection care cascade to identify ways to improve TB infection care delivery. STUDY DESIGN: We conducted a retrospective cohort study of children (age <18 years) screened for TB within 2 Boston-area health systems between January 2017 and May 2019. Patients who received a tuberculin skin test (TST) and/or an interferon gamma release assay (IGRA) were included. RESULTS: We included 13 353 tests among 11 622 patients; 93.9% of the tests were completed. Of 199 patients with positive tests for whom TB infection evaluation was clinically appropriate, 59.3% completed treatment or were recommended to not start treatment. Age 12-17 years (vs < 5 years; aOR 1.59; 95% CI, 1.32-1.92), non-English/non-Spanish language preference (vs English; aOR, 1.34; 95% CI, 1.02-1.76), and receipt of an IGRA (vs TST, aOR, 30.82; 95% CI, 21.92-43.34) were associated with increased odds of testing completion. Odds of testing completion decreased as census tract social vulnerability index quartile increased (ie, social vulnerability worsened; most vulnerable quartile vs least vulnerable quartile, aOR, 0.77; 95% CI, 0.60-0.99). Odds of completing treatment after starting treatment were higher in females (vs males; aOR, 2.35; 95% CI, 1.14-4.85) and were lower in patients starting treatment in a primary care clinic (vs TB/infectious diseases clinic; aOR, 0.44; 95% CI, 0.27-0.71). CONCLUSIONS: Among children with a high proportion of negative TB infection tests, completion of testing was high, but completion of evaluation and treatment was moderate. Transitions toward IGRA testing will improve testing completion; interventions addressing social determinants of health are important to improve treatment completion.