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PurposeGlobally, transgender women (TGW) experience wide-ranging barriers to health and care, with disproportionately high risks of infectious and chronic diseases. Despite these vulnerabilities, research on access to care for transgender populations in low- and middle-income countries is extremely limited. Furthermore, existing studies have primarily focused on human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), with less emphasis on TGW’s broader health needs. This study analyzed patterns of morbidity and health service uptake among TGW in Lima, Peru. The purpose was to better understand health outreach and service needs to inform targeting and design of future community-level interventions.MethodsThis cross-sectional study surveyed a convenience sample of 301 TGW in metropolitan Lima, Peru. Data was collected between September – October 2020. This paper provides descriptive statistics and results of bivariate and multivariable regression models.ResultsHealth coverage and access to care were suboptimal. Less education and older age were positively associated with illness and HIV and tuberculosis (TB) testing. Gender identity sub-group (i.e., woman, trans or transgender, transsexual, “transformista,” “travesti,” and other) was associated with HIV testing and pre-exposure prophylaxis (PrEP) usage. Both awareness of and interest in PrEP were low, as was usage among those who were interested in taking PrEP.ConclusionFuture public health efforts should be tailored to meet the diverse needs of TGW, expand TB testing, bridge the gap between PrEP interest and use, and increase insurance coverage and access to trans-friendly services to promote improved health outcomes.

Background Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion. Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid. Methods Multicentre (16 countries), prospective, observational study reporting incidence and frequency of clinically relevant adverse events of special interest (AESIs) among patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent. Results Among 2296 patients, the most common clinically relevant AESIs were peripheral neuropathy (26.4%), electrolyte depletion (26.0%), and hearing loss (13.2%) with an incidence per 1000 person months of treatment, 1000 person-months of treatment 21.5 (95% confidence interval [CI]: 19.8–23.2), 20.7 (95% CI: 19.1–22.4), and 9.7 (95% CI: 8.6–10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4–2.3)/1000 person-months of treatment. Patients receiving injectables (N = 925) and linezolid (N = 1826) were most likely to experience events during exposure. Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95% CI: 66.0–80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis, and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9–24.8) times/1000 patient-months of linezolid exposure. Conclusions AEs often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring and drug durations should reflect expected safety profiles of drug combinations. Clinical Trials Registration NCT03259269.

Objectives Uncovering and addressing disparities in infectious disease outbreaks require a rapid, methodical understanding of local epidemiology. We conducted a seroprevalence study of SARS-CoV-2 infection in Holyoke, Massachusetts, a majority Hispanic city with high levels of socio-economic disadvantage to estimate seroprevalence and identify disparities in SARS-CoV-2 infection. Methods We invited 2000 randomly sampled households between 11/5/2020 and 12/31/2020 to complete questionnaires and provide dried blood spots for SARS-CoV-2 antibody testing. We calculated seroprevalence based on the presence of IgG antibodies using a weighted Bayesian procedure that incorporated uncertainty in antibody test sensitivity and specificity and accounted for household clustering. Results Two hundred eighty households including 472 individuals were enrolled. Three hundred twenty-eight individuals underwent antibody testing. Citywide seroprevalence of SARS-CoV-2 IgG was 13.1% (95% CI 6.9–22.3) compared to 9.8% of the population infected based on publicly reported cases. Seroprevalence was 16.1% (95% CI 6.2–31.8) among Hispanic individuals compared to 9.4% (95% CI 4.6–16.4) among non-Hispanic white individuals. Seroprevalence was higher among Spanish-speaking households (21.9%; 95% CI 8.3–43.9) compared to English-speaking households (10.2%; 95% CI 5.2–18.0) and among individuals in high social vulnerability index (SVI) areas based on the CDC SVI (14.4%; 95% CI 7.1–25.5) compared to low SVI areas (8.2%; 95% CI 3.1–16.9). Conclusions The SARS-CoV-2 IgG seroprevalence in a city with high levels of social vulnerability was 13.1% during the pre-vaccination period of the COVID-19 pandemic. Hispanic individuals and individuals in communities characterized by high SVI were at the highest risk of infection. Public health interventions should be designed to ensure that individuals in high social vulnerability communities have access to the tools to combat COVID-19.

BACKGROUND: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. METHODS: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. FINDINGS: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. INTERPRETATION: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. FUNDING: WHO, US National Institutes of Health.

IntroductionAdolescents living with HIV (ALWH) experience higher mortality rates compared to other age groups, exacerbated by suboptimal transition from pediatric to adult HIV care in which decreased adherence to antiretroviral treatment (ART) and unsuppressed viremia are frequent. Care transition—a process lasting months or years—ideally prepares ALWH for adult care and can be improved by interventions that are youth-friendly and address psychosocial issues affecting ART adherence; however, such interventions are infrequently operationalized. Community-based accompaniment (CBA), in which laypeople provide individualized support and health system navigation, can improve health outcomes among adults with HIV. Here, we describe patient and provider perceptions of a novel HIV CBA intervention called “PASEO” for ALWH in Lima, Peru.MethodsPASEO consisted of six core elements designed to support ALWH before, during, and after transition to adult HIV care. Community-based health workers provided tailored accompaniment for ALWH aged 15-21 years over 9 months, after which adolescent participants were invited to provide feedback in a focus group or in-depth interview. HIV care personnel were also interviewed to understand their perspectives on PASEO. A semi-structured interview guide probing known acceptability constructs was used. Qualitative data were analyzed using a Framework Analysis approach and emergent themes were summarized with illustrative quotes.ResultsWe conducted 5 focus groups and 11 in-depth interviews among N=26 ALWH and 9 key-informant interviews with HIV care personnel. ALWH participants included those with both vertically- and behaviorally acquired HIV. ALWH praised PASEO, attributing increased ART adherence to the project. Improved mental health, independence, self-acceptance, and knowledge on how to manage their HIV were frequently cited. HIV professionals similarly voiced strong support of PASEO. Both ALWH and HIV professionals expressed hope that PASEO would be scaled. HIV professionals voiced concerns regarding financing PASEO in the future.ConclusionA multicomponent CBA intervention to increase ART adherence among ALWH in Peru was highly acceptable by ALWH and HIV program personnel. Future research should determine the efficacy and economic impact of the intervention.

BackgroundMany children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Diagnostic challenges in children include low bacterial burden, challenges around specimen collection, and limited access to diagnostic expertise. Algorithms that guide decisions to initiate tuberculosis treatment in resource-limited settings could help to close the persistent childhood tuberculosis treatment gap. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies conducted to date have been small and localised, with limited generalizability.MethodsWe collated individual participant data including clinical, bacteriological, and radiologic information from prospective diagnostic studies in high-tuberculosis incidence settings enrolling children FindingsOf 4,718 children from 13 studies from 12 countries, 1,811 (38·4%) were classified as having pulmonary tuberculosis; 541 (29·9%) bacteriologically confirmed and 1,270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. Our prediction model had a combined sensitivity of 86% [95% confidence interval (CI): 0·68-0·94] and specificity of 37% [95% CI: 0·15-0·66] against a composite reference standard.InterpretationWe adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in resource-limited, primary healthcare settings to initiate tuberculosis treatment in children in order to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents.FundingWorld Health Organization, US National Institutes of HealthRESEARCH IN CONTEXTEvidence before the studyTreatment-decision algorithms relate information gained in the evaluation of children into an assessment of tuberculosis disease risk and empower healthcare workers to make appropriate treatment decisions. Studies in primary healthcare centres have demonstrated that use of treatment-decision algorithms can improve childhood pulmonary tuberculosis case-detection and treatment initiation in settings with high-tuberculosis incidence. To identify primary research studies on treatment-decision algorithm performance evaluation and/or development for childhood pulmonary tuberculosis, we carried out a PubMed search using the terms (‘child*’ OR ‘paediatr*’ OR ‘pediatr*’) AND (‘tuberculosis’ OR ‘TB’) AND (‘treatment-decision’ OR ‘algorithm’ OR ‘diagnos*’) to identify primary research published in any language prior to 29 June 2022.We additionally consulted multiple experts in childhood pulmonary tuberculosis diagnosis and management, and we referred to existing, published reviews of treatment-decision algorithms. With respect to treatment-decision algorithm performance, several studies have retrospectively estimated the performance of treatment-decision algorithms in a single geographic setting; a subset of these studies have also compared the performance of multiple algorithms using data from a single geographic setting. With respect to treatment-decision algorithm development, many existing algorithms have been developed without explicit analysis of data from children with presumptive pulmonary tuberculosis, often developed from expert consensus. Gunasekera et al. used model-based approaches to analyse diagnostic evaluations data (e.g., clinical history, physical examination, chest radiograph, and results from rapid molecular and culture testing for Mycobacterium tuberculosis) collected from children with presumptive pulmonary tuberculosis in a single geographic setting to inform the development of a diagnostic algorithm while Marcy et al. and Fourie et al analysed data from multiple geographic settings. However, these studies were relatively small with limited assessment of generalisability.Added value of this studyWe collated individual participant data from 13 prospective diagnostic studies from 12 countries including 4,718 children with presumptive pulmonary tuberculosis from geographically diverse settings with a high incidence of tuberculosis in order to 1) evaluate the performance of existing treatment-decision algorithms and 2) develop multivariable logistic regression models to quantify the contribution of individual features to discriminate tuberculosis from non-tuberculosis. A panel of child tuberculosis experts provided input into performance targets and advised on how to incorporate scores derived from these models into pragmatic treatment-decision algorithms to assist in the evaluation of children presenting with presumptive pulmonary tuberculosis in primary healthcare centres.Implications of all the available evidenceOur findings suggest that evidence-based, pragmatic treatment-decision algorithms can be developed to make sensitive and clinically appropriate decisions to treat a child with pulmonary tuberculosis. Although the specificity does not reach optimal targets for childhood tuberculosis diagnosis, pragmatic treatment-decision algorithms provide clinically relevant guidance that can empower health workers to start children on tuberculosis treatment at the primary healthcare setting and will likely contribute to reducing the case-detection gap in childhood tuberculosis. External, prospective evaluation of these novel algorithms in diverse settings is required, including assessment of their accuracy, feasibility, acceptability, impact, and cost-effectiveness. This work led to a new interim WHO recommendation to support the use of treatment-decision algorithms in the evaluation of children with presumptive tuberculosis in the 2022 updated consolidated guidelines on the management of tuberculosis in children. Two algorithms developed from this work have been included in the WHO operational handbook accompanying these guidelines.

BackgroundFood insecurity has been independently associated with cholera infection and there is an inverse relationship between national food security and annual cholera incidence. However, factors that mediate increased cholera risk among food insecure households remain largely unexplored.MethodsIn a cross-sectional survey of rural households in Haiti, we explored the role of food behaviors (i.e., dietary choices and food-handling practices) as mediators of cholera risk among food-insecure families. We generated multivariable regression models to test hypothesized associations between severity of food insecurity (measured by the Household Hunger Scale), hygiene and food behaviors, and history of severe, medically-attended cholera.ResultsCompared with little to no household hunger, moderate hunger (Adjusted Odds Ratio [AOR] 1.62, 95% Confidence Interval (CI) 1.12—2.36; p=0.011) and severe hunger (AOR 2.32, 95% CI 1.27—4.22; p=0.006) were positively associated with history of severe, medically-attended cholera. Household hunger was positively associated with three behaviors: antacid use, consumption of leftover non-reheated food, and eating food and beverages prepared outside of the home (i.e., at a restaurant or from a vendor). Consumption of outside food items and antacid use were positively associated with a history of cholera.ConclusionOur findings suggest that food behaviors may mediate the association between food insecurity and cholera and contribute to an understanding of how interventions could be designed to target food insecurity as part of cholera prevention and control.Author summaryFood insecurity has been found to be a risk factor for cholera at the household and national level;[1–3] however the mechanism through which food insecurity may increase the risk of cholera remains unknown.In a large cross-sectional survey of 1072 households in rural Haiti, we observed a robust independent association between food insecurity—defined as a persistent lack of access to food in adequate quantity or quality and measured by the Household Hunger Scale—and severe, medically-attended cholera. This relationship appears to be linear, conferring a dose-dependent risk of cholera by severity of food insecurity. We found household food insecurity to be associated with three high-risk behaviors: antacid use, consumption of leftover non-reheated food, and eating food and beverages prepared outside of the home. Two high-risk behaviors—including antacid use and consumption food and beverages prepared outside of the home (i.e., at a restaurant or from a vendor)—were independent risk factors for cholera.High-risk food handling practices may be one causal pathway whereby food insecurity increases risk of cholera infection. Future longitudinal and qualitative studies should investigate whether interventions targeting food insecurity could reduce cholera risk among populations who face a high burden of both conditions.

We piloted a community-based intervention to improve outcomes among adolescents living with HIV who were transitioning to adult-oriented care in Lima, Peru. We assessed feasibility and potential effectiveness, including within-person changes in self-reported adherence, psychosocial metrics (NIH Toolbox), and transition readiness ("Am I on TRAC" questionnaire, "Got Transition" checklist). From October 2019 to January 2020, we enrolled 30 adolescents (15-21 years). The nine-month intervention consisted of logistical, adherence and social support delivered by entry-level health workers and group sessions to improve health-related knowledge and skills and social support. In transition readiness, we observed within-person improvements relative to baseline. We also observed strong evidence of improvements in adherence, social support, self-efficacy, and stress, which were generally sustained three months post-intervention. All participants remained in treatment after 12 months. The intervention was feasible and potentially effective for bridging the transition to adult HIV care. A large-scale evaluation, including biological endpoints, is warranted.Piloteamos una intervención comunitaria para mejorar los resultados de adolescentes viviendo con el VIH que se encontraban en transición a la atención de VIH orientada a adultos en Lima, Perú. Evaluamos la viabilidad y la eficacia potencial, incluidos los cambios personales en la adherencia auto-reportada, criterios psicosociales (NIH Toolbox), y preparación para la transición (cuestionario “Estoy en el TRAC”, lista de verificación “Got Transition”). Desde octubre de 2019 hasta enero de 2020, enrolamos a 30 adolescentes (15 a 21 años). La intervención de nueve meses consistió en apoyo logístico, de adherencia y social brindado por técnicos de enfermería y sesiones grupales para mejorar tanto el conocimiento y las habilidades relacionados con la salud, como el apoyo social. En cuanto a la preparación para la transición, observamos mejoras comparada con el basal. También observamos una fuerte evidencia de mejoras en la adherencia, apoyo social, autoeficacia y estrés, que se mantuvieron, generalmente, tres meses después del fin de la intervención. Todos los participantes seguían en tratamiento después de 12 meses. La intervención fue factible y potencialmente efectiva para tender un puente en la transición a la atención del VIH para adultos. Esto amerita una evaluación a mayor escala y que incluya criterios clínicos.

We examined reporting agreement of oral, vaginal, and anal sex in adolescents and young adults living with perinatally-acquired HIV and those perinatally HIV-exposed and uninfected in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) and AMP Up studies. Agreement between fixed constructs (e.g., age at first sex) and prevalence of logical inconsistencies (e.g., reclaimed virginity status) over time were assessed. Internal consistency was also examined using an attention check question and questions regarding condom use in the prior three months. Those who reported having anal sex in adolescence had a higher proportion of inconsistent responses compared to vaginal and oral sex measures. At their most recent survey, 84% of young adults correctly answered an attention check question and 74% agreed within the survey on condom use in the prior three months. In bivariate analyses, HIV status was not associated with responding inconsistently. Increased time between surveys, male sex, and younger age at first survey were associated with multiple measures of inconsistency over time, while lower cognitive scores, having less than a high school diploma, and negatively answering post-survey acceptability questions were associated with incorrectly answering an attention check question.

Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study. We used pooled logistic regression to estimate the observational analogue of the intention-to-treat effect (aITT) adjusting for baseline confounders and to estimate the observational analogue of the per-protocol effect (aPP) using inverse probability of censoring weighting to control for time-varying confounding. At treatment initiation, 362 patients received three likely effective drugs (delamanid-free) or three likely effective drugs plus delamanid (delamanid-containing). Over 80% of patients received two to three Group A drugs (bedaquiline, linezolid, moxifloxacin/levofloxacin) in their regimen. We found no evidence the addition of delamanid to a three-drug regimen increased two-month (aITT relative risk: 0.90 (95% CI: 0.73–1.11), aPP relative risk: 0.89 (95% CI: 0.66–1.21)) or six-month culture conversion (aITT relative risk: 0.94 (95% CI: 0.84, 1.02), aPP relative risk: 0.93 (95% CI: 0.83, 1.04)). In regimens containing combinations of three likely effective, highly active anti-TB drugs the addition of delamanid had no discernible effect on culture conversion at two or six months. As the standard of care for MDR/RR-TB treatment becomes more potent, it may become increasingly difficult to detect the benefit of adding a single agent to standard of care MDR/RR-TB regimens. Novel approaches like those implemented may help account for background regimens and establish effectiveness of new chemical entities.

Background Food insecurity has been independently associated with developing cholera and there is an inverse relationship between national food security and annual cholera incidence. However, the factors that mediate the risk of cholera among food insecure households remain largely unexplored. Methodology and principal findings In a cross-sectional survey of rural households in Haiti, we explored the role of food behaviors (i.e., dietary choices and food-handling practices) as mediators of cholera risk among food-insecure families. We generated a series of multivariable regression models to test hypothesized associations between the severity of food insecurity (measured by the Household Hunger Scale), hygiene and food behaviors, and history of severe, medically-attended cholera. Moderate household hunger (Adjusted Odds Ratio [AOR] 1.47, 95% Confidence Interval (CI) 1.05–2.04; p = 0.021) and severe hunger (AOR 2.45, 95% CI 1.45–4.15; p = 0.001) were positively associated with a history of severe, medically-attended cholera compared with little to no household hunger. Household hunger was positively associated with three behaviors: antacid use, consumption of leftover non-reheated food, and eating food and beverages prepared outside of the home (i.e., at a restaurant or from a vendor). Consumption of outside food items and antacid use were positively associated with a history of cholera. Conclusion Our findings suggest that food behaviors may mediate the association between food insecurity and cholera and contribute to an understanding of how interventions could be designed to target food insecurity as part of cholera prevention and control.

BACKGROUND: Timely diagnosis and treatment of pediatric tuberculosis (TB) is critical to reducing mortality but remains challenging in the absence of adequate diagnostic tools. Even once a TB diagnosis is made, delays in treatment initiation are common, but for reasons that are not well understood.METHODS: To examine reasons for delay post-diagnosis, we conducted semi-structured interviews with Ministry of Health (MoH) physicians and field workers affiliated with a pediatric TB diagnostic study, and caregivers of children aged 0–14 years who were diagnosed with pulmonary TB in Lima, Peru. Interviews were analyzed using systematic comparative and descriptive content analysis.RESULTS: We interviewed five physicians, five field workers and 26 caregivers with children who initiated TB treatment < 7 days after diagnosis (n = 15) or who experienced a delay of ≥7 days (n = 11). Median time in delay from diagnosis to treatment initiation was 26 days (range 7–117). Reasons for delay included: health systems challenges (administrative hurdles, medication stock, clinic hours), burden of care on families and caregiver perceptions of disease severity.CONCLUSION: Reasons for delay in treatment initiation are complex. Interventions to streamline administrative processes and tools to identify and support families at risk for delays in treatment initiation are urgently needed.

Tuberculosis (TB) diagnosis relies on a sputum sample, which cannot be easily obtained from all symptomatic patients. Mycobacterium tuberculosis DNA can be detected from oral swabs, a noninvasive, safe alternative sample type; however, reported sensitivities have been variable and likely depend on sample collection, processing procedures and host characteristics. We analyzed three buccal swab samples from 123 adults with culture-confirmed TB in Lima, Peru. We compared the sensitivity and specificity of two sample collection devices (OmniSwab and EasiCollect FTA cards) and examined factors associated with detection. DNA was extracted with a commercially available kit and detected via real-time PCR IS6110 amplification. Overall sensitivity for buccal samples was 51% (95% Confidence Interval [CI] 42–60%). Specificity from a single sample among healthy controls was 96.7% (95% CI 83–99.9%). Positive sputum smear and cavitary disease, correlates of disease burden, were associated with detection via buccal swab. Although we observed higher sensitivities with the Omniswab samples, this appeared to be due primarily to differences in patient characteristics (e.g., cavitary disease). Overall, our findings support the potential for a buccal sample-based TB assay. Future work should focus on assay optimization and streamlining the assay workflow.

Clinical outcomes among adolescents living with HIV (ALHIV) might be improved by interventions aimed at addressing limited health literacy. We developed a Spanish-language rap video on HIV concepts and examined its acceptability and feasibility as a learning tool among ALHIV in Lima, Peru. Twenty-eight ALHIV receiving care at an urban pediatric hospital and ten stakeholders engaged in the care of adolescents watched the video. Adolescents completed a pre- and post-video questionnaire. We conducted focus groups with ALHIV and in-depth interviews with stakeholders and analyzed transcripts to identify themes. ALHIV described concepts of CD4 cell count and viral load as they were portrayed. Participants reported the video was relatable, accessible, and provided hope that ALHIV could lead healthy lives and advocated for future videos to address topics such as transmission and sexual health. Questionnaires indicated some improvement in viral load knowledge. An HIV health literacy music video intervention was feasible to implement and accepted by ALHIV and their healthcare providers. Communicating HIV knowledge via music videos may be promising; further study is needed to optimize implementation.Los resultados clínicos entre los adolescentes que viven con el VIH (AVVIH) podrían mejorarse mediante intervenciones dirigidas a abordar la limitada alfabetización sanitaria. Desarrollamos un video de rap en español sobre los conceptos del VIH y examinamos su aceptabilidad y viabilidad como herramienta de aprendizaje entre los AVVIH en Lima, Perú. Veintiocho AVVIH que reciben atención en un hospital pediátrico urbano y diez interesados involucrados en la atención de adolescentes vieron el video. Los adolescentes completaron un cuestionario previo y posterior al video. Realizamos grupos focales con AVVIH y entrevistas a profundidad a los interesados y analizamos las transcripciones para identificar los temas. Los AVVIH describieron conceptos de recuento de células CD4 y carga viral tal como se retrataron. Los participantes informaron que el video era identificable, accesible y brindaba la esperanza de que los AVVIH pudiera llevar una vida saludable y abogaron por videos futuros para abordar temas como la transmisión y la salud sexual. Los cuestionarios indicaron cierta mejora en el conocimiento de la carga viral. Una intervención de video musical para educación en salud sobre el VIH fue factible de implementar y fue aceptada por los AVVIH y sus proveedores de atención médica. La comunicación de conocimientos sobre el VIH a través de videos musicales puede ser prometedora; se necesitan más estudios para optimizar la implementación.

Randomized clinical trials represent the gold standard in therapeutic research. Nevertheless, observational cohorts of patients treated for multidrug-resistant TB (MDR-TB) or rifampin-resistant TB (RR-TB) also play an important role in generating evidence to guide drug-resistant TB care. Generally, summary exposure classifications (e.g., ‘ever vs. never´, ‘exposed at baseline´) have been used to characterize drug exposure in the absence of detailed longitudinal data on MDR-TB regimen changes. These summary classifications, along with an absence of data on covariates that change throughout the course of treatment, constrain researchers´ ability to answer the most relevant questions while accounting for known biases. In this paper, we highlight the importance of regimen changes in improving inference from observational studies of longer MDR-TB treatment regimens, and offer an overview of the data and analytic strategies required to do so.

In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015–2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.

Objectives: In Sierra Leone, very little data are available on hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalence. Blood donor screening permits estimation of the prevalence of transfusion transmissible infections in a general open population. We analyzed blood donor data in Sierra Leone to estimate national viral hepatitis prevalence and identify risk factors for hepatitis infection among the donor population. Methods: We conducted a retrospective data analysis in five government hospitals. We collected HBV and HCV screening results, donor demographics, and donation type (family replacement or voluntary donor; first-time or repeat). Univariate and multivariate analyses were performed to determine associations between infections and socio-demographic factors. Results: The number of donors screened was 29,713. The overall prevalence was: 10.8% (3200) for HBV and 1.2% (357) for HCV. HBV infection was most strongly associated with male sex (p

We report severe acute respiratory syndrome coronavirus 2 antibody positivity among market and city bus depot workers in Lima, Peru. Among 1285 vendors from 8 markets, prevalence ranged from 27% to 73%. Among 488 workers from 3 city bus depots, prevalence ranged from 11% to 47%. Self-reported symptoms were infrequent. National Institute of Allergy and Infectious Diseases Revisión por pares

Background Conversion of sputum culture from positive to negative for M. tuberculosis is a key indicator of treatment response. An initial positive culture is a pre-requisite to observe conversion. Consequently, patients with a missing or negative initial culture are excluded from analyses of conversion outcomes. To identify the initial, or “baseline” culture, researchers must define a sample collection interval. An interval extending past treatment initiation can increase sample size but may introduce selection bias because patients without a positive pre-treatment culture must survive and remain in care to have a culture in the post-treatment interval. Methods We used simulated data and data from the endTB observational cohort to investigate the potential for bias when extending baseline culture intervals past treatment initiation. We evaluated bias in the proportion with six-month conversion. Results In simulation studies, the potential for bias depended on the proportion of patients missing a pre-treatment culture, proportion with conversion, proportion culture positive at treatment initiation, and proportion of patients missing a pre-treatment culture who would have been observed to be culture positive, had they had a culture. In observational data, the maximum potential for bias when reporting the proportion with conversion reached five percentage points in some sites. Conclusion Extending the allowable baseline interval past treatment initiation may introduce selection bias. If investigators choose to extend the baseline collection interval past treatment initiation, the proportion missing a pre-treatment culture and the number of deaths and losses to follow up during the post-treatment allowable interval should be clearly enumerated.

Background Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs. Methods We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented. Results Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 patients (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died, and 7.2% experienced treatment failure. Conclusions Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.

IntroductionEffective strategies to increase pre-exposure prophylaxis (PrEP) uptake and continuation among adolescent girls and young women (AGYW) who engage in sex work or transactional sex are sparsely reported. We aimed to describe the available evidence on strategies for improving the uptake and continuation of PrEP among AGYW who engage in sex work or transactional sex, or otherwise are at high risk of acquiring HIV, and report their implementation outcomes.MethodPubMed, Embase, CINAHL and Global Health were searched for studies describing strategies to increase uptake and continuation of PrEP for HIV prevention among AGYW at high risk of acquiring HIV in low-income and middle-income countries. Two independent reviewers screened citations for inclusion and performed data abstraction. Proctor’s framework was used to report the implementation outcomes of the interventions.ResultWe identified 1046 citations, and reviewed 69 full-text documents, of which we included 11 in the scoping review. A social marketing campaign was used in one study to create demand for PrEP. A decision support tool was used in one study to improve PrEP initiation. SMS reminders (two studies), drug-level feedback (two studies), peer group support (one study) and conditional economic incentives (one study) were used to improve PrEP continuation. Five studies reported adoption outcomes, two of which were high. Four studies reported sustainability outcomes; these were low or moderate. One study found private youth-friendly clinics a better fit for AGYW PrEP delivery compared with public hospitals, and prescription of PrEP by non-study staff in the hospital facility was low.ConclusionMultiple promising interventions have been used to deliver PrEP to AGYW at high risk of acquiring HIV; however, more information is needed to understand how these interventions would likely perform at scale outside of a research context.

BackgroundSeroprevalence studies are important tools to estimate the prevalence of prior or recent SARS-CoV-2 infections, identifying hotspots and high-risk groups and informing public health responses to the COVID-19 pandemic. We conducted a city-level seroprevalence study in Holyoke, Massachusetts, USA to estimate the seroprevalence of SARS-CoV-2 antibodies and risk factors for seropositivity.MethodsWe invited inhabitants of 2,000 randomly sampled addresses between November 5 and December 31, 2020. Participants completed questionnaires measuring sociodemographic and health characteristics, and COVID-19 exposure history, and provided dried blood spots for measurement of SARS-CoV-2 IgG and IgM antibodies. We calculate total and subgroup seroprevalence estimates based on presence of IgG antibodies using a Bayesian procedure that incorporates uncertainty in antibody test sensitivity and specificity. We account for clustering by household and weighting based on demographic characteristics to ensure estimates represented the city’s population.FindingsWe enrolled 280 households including 472 individuals. 328 underwent antibody testing. The citywide seroprevalence estimate of SARS-CoV-2 IgG was 13.1% (95%CI 6.9-22.3) compared to 9.8% based on publicly reported case counts. Seroprevalence was 16.1% (95%CI 6.2-31.8) among individuals identifying as Hispanic compared to 9.4% (95%CI 4.6-16.4) among those identifying as non-Hispanic white. Seroprevalence was higher among Spanish speaking households (21.9%; 95% CI 8.3-43.9) compared to English speaking households (10.2%; 95% CI 5.2-18.0) and among individuals living in high vulnerability areas (14.4%; 95% CI 7.1-25.5) compared to low vulnerability areas (8.2%; 95% CI 3.1-16.9).InterpretationThe measured SARS-CoV-2 seroprevalence of IgG antibodies in Holyoke was only 13.1% during the second surge of SARS-CoV-2 in this region, far from accepted thresholds for “herd immunity.” Already vulnerable communities were at highest risk of prior infection. Implementation of local serosurveys in tandem with proactive public health interventions that address disparities in SARS-CoV-2 exposure are crucial to ensure at-risk communities have appropriate educational materials and access to vaccines, testing, and timely treatment.FundingThe Sullivan Family Foundation, Harvard Data Science Institute Bias2program, the US Centers for Disease Control and Prevention.