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Background: Rapid IgM/IgG antibody tests were largely used in lieu of RT-PCR tests as part of COVID-19 public health response activities in Lima, Peru. To assess their utility, we explored the relationship between the time since onset of several COVID-19-related symptoms and the sensitivity of a rapid combined IgM/IgG antibody test., Methods: We collected data from a community sample of individuals (n = 492) who received concurrent RT-PCR and rapid IgM/IgG antibody testing between May 2020 and March 2021. We estimated the sensitivity of the antibody test, against the RT-PCR test, by weeks since symptom onset via segmented regression analysis., Results: The overall sensitivity of the rapid IgM/IgG antibody test was 46.7% (95% CI, 42.4-51.2%). Among 372 (75.6%) participants who reported COVID-19-related symptoms, sensitivity increased from 30.4% (95% CI, 24.7-36.6%) in week 1 after symptom onset to 83.3% (95% CI, 41.6-98.4%) in week 4. The test sensitivity increased by 31.9% (95% CI, 24.8-39.0%) per week until week 2 to 3, then decreased by - 6.0% (95% CI, - 25.7-13.7%) per week thereafter., Conclusion: Rapid antibody tests are a poor substitute for RT-PCR testing, regardless of presenting symptoms. This highlights the need for future pandemic planning to include timely and equitable access to gold-standard diagnostics, treatment, and vaccination., (© 2023. The Author(s).)

Point-of-care antigen-detecting rapid diagnostic tests (RDTs) to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represent a scalable tool for surveillance of active SARS-CoV-2 infections in the population. Data on the performance of these tests in real-world community settings are paramount to guide their implementation to combat the COVID-19 pandemic. We evaluated the performance characteristics of the CareStart COVID-19 Antigen test (CareStart) in a community testing site in Holyoke, Massachusetts. We compared CareStart to a SARS-CoV-2 reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) reference, both using anterior nasal swab samples. We calculated the sensitivity, specificity, and the expected positive and negative predictive values at different SARS-CoV-2 prevalence estimates. We performed 666 total tests on 591 unique individuals. 573 (86%) were asymptomatic. There were 52 positive tests by RT-qPCR. The sensitivity of CareStart was 49.0% (95% Confidence Interval (CI) 34.8-63.4) and specificity was 99.5% (95% CI 98.5-99.9). Among positive RT-qPCR tests, the median cycle threshold (Ct) was significantly lower in samples that tested positive on CareStart. Using a Ct ≤ 30 as a benchmark for positivity increased the sensitivity of the test to 64.9% (95% CI 47.5-79.8). Our study shows that CareStart has a high specificity and moderate sensitivity. The utility of RDTs, such as CareStart, in mass implementation should prioritize use cases in which a higher specificity is more important, such as triage tests to rule-in active infections in community surveillance programs., (© 2022. The Author(s).)

Introduction: Effective 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., Method: PubMed, 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., Result: We 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., Conclusion: Multiple 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022. The Author(s).)

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., Competing Interests: Potential conflicts of interest. Bedaquiline donations made from Janssen to the Global Drug Facility were used for patients in the endTB observational study. Donations of delamanid from Otsuka were used for initial patients enrolled in the endTB Observational Study. The companies from which drug donations were received did not have any role on the study design, data analyses, data interpretation or manuscript writing. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Widely available and reliable testing for SARS-CoV-2 is essential for the public health response to the COVID-19 pandemic. We estimated the diagnostic performance of reverse transcription PCR (RT-PCR) performed on saliva and the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab compared to the reference standard, nasopharyngeal swab (NP) RT-PCR. We enrolled participants living and/or seeking care in health facilities in North Lima, Peru from November 2020 to January 2021. Consenting participants underwent same-day RT-PCR on both saliva and nasopharyngeal swab specimens, antigen testing on a nasopharyngeal swab specimen, pulse oximetry, and standardized symptom assessment. We calculated sensitivity, specificity, and predictive values for the nasopharyngeal antigen and saliva RT-PCR compared to nasopharyngeal RT-PCR. Of 896 participants analyzed, 567 (63.3%) had acute signs/symptoms of COVID-19. The overall sensitivity and specificity of saliva RT-PCR were 85.8% and 98.1%, respectively. Among participants with and without acute signs/symptoms of COVID-19, saliva sensitivity was 87.3% and 37.5%, respectively. Saliva sensitivity was 97.4% and 56.0% among participants with cycle threshold ( C T ) values of ≤30 and >30 on nasopharyngeal RT-PCR, respectively. The overall sensitivity and specificity of nasopharyngeal antigen were 73.2% and 99.4%, respectively. The sensitivity of the nasopharyngeal antigen test was 75.1% and 12.5% among participants with and without acute signs/symptoms of COVID-19, and 91.2% and 26.7% among participants with C T values of ≤30 and >30 on nasopharyngeal RT-PCR, respectively. Saliva RT-PCR achieved the WHO-recommended threshold of >80% for sensitivity for the detection of SARS-CoV-2, while the SD Biosensor nasopharyngeal antigen test did not. IMPORTANCE In this diagnostic validation study of 896 participants in Peru, saliva reverse transcription PCR (RT-PCR) had >80% sensitivity for the detection of SARS-CoV-2 among all-comers and symptomatic individuals, while the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab had <80% sensitivity, except for participants whose same-day nasopharyngeal RT-PCR results showed cycle threshold values of <30, consistent with a high viral load in the nasopharynx. The specificity was high for both tests. Our results demonstrate that saliva sampling could serve as an alternative noninvasive technique for RT-PCR diagnosis of SARS-CoV-2. The role of nasopharyngeal antigen testing is more limited; when community transmission is low, it may be used for mass screenings among asymptomatic individuals with high testing frequency. Among symptomatic individuals, the nasopharyngeal antigen test may be relied upon for 4 to 8 days after symptom onset, or in those likely to have high viral load, whereupon it showed >80% sensitivity.

Objectives: This mixed-method study aimed to understand the effectiveness of linkage to biopsy and treatment in women with a high-risk mammography result (Breast Imaging Reporting and Data System, BI-RADS 4 and 5) in the national telemammography programme and to explore women's experiences during this process., Setting: Quantitative component: we collected and linked health data from the telemammography reading centre, the national public health insurance, the national centre for disease control and the national referral cancer centre. Qualitative component: we interviewed participants from different regions of the country representing diverse social and geographical backgrounds., Participants: Quantitative: women who underwent telemammography between July 2017 and September 2018 and had high-risk results (BI-RADS 4-5) were collected. Qualitative: women with a high-risk telemammography result, healthcare providers and administrators., Outcomes Measures: Quantitative: we determined biopsy and treatment linkage rates and delays. Qualitative: we explored barriers and facilitators for obtaining a biopsy and initiating treatment., Results: Of 126 women with high-risk results, 48.4% had documentation of biopsy and 37.5% experienced a delay of >45 days to biopsy. Of 51 women diagnosed with breast cancer, 86.4% had evidence of treatment initiation, but 69.2% initiated treatment >45 days after biopsy. Travelling to major cities for care, administrative factors and breast cancer misconceptions, among other factors, impeded timely, continuous care for breast cancer. A multidisciplinary and culturally tailored patient education facilitated understanding of the disease and prompt decision making about subsequent medical care., Conclusions: Strengthened breast cancer care capacity outside the capital city, standardised referral pathways, ensured financial support for travel expenses, and enhanced patient education are required to secure linkage to the breast cancer care continuum. Robust information systems are needed to track patients and to evaluate the programme's performance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent World Health Organization guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline and/or delamanid as part of their multidrug regimen., Methods: Patients with a positive baseline culture were included. 6-month culture conversion was defined as two consecutive negative cultures collected >15 days apart. We derived predicted probabilities of culture conversion and relative risk using marginal standardisation methods., Results: Culture conversion was observed in 83.8% (526 out of 628) of patients receiving an all-oral regimen and 85.5% (425 out of 497) of those receiving an injectable-containing regimen. The adjusted relative risk comparing injectable-containing regimens to all-oral regimens was 0.96 (95% CI 0.88-1.04). We found very weak evidence of effect modification by HIV status: among patients living with HIV, there was a small increase in the frequency of conversion among those receiving an injectable-containing regimen, relative to an all-oral regimen, which was not apparent in HIV-negative patients., Conclusions: Among individuals receiving bedaquiline and/or delamanid as part of a multidrug regimen for drug-resistant tuberculosis, there was no significant difference between those who received an injectable and those who did not regarding culture conversion within 6 months. The potential contribution of injectable agents in the treatment of drug-resistant tuberculosis among those who were HIV positive requires further study., Competing Interests: Conflict of interest: P.Y. Khan reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: M.F. Franke reports grants from Unitaid, during the conduct of the study. Conflict of interest: C. Hewison reports grants from Unitaid, during the conduct of the study. Conflict of interest: K.J. Seung reports grants from Unitaid, during the conduct of the study. Conflict of interest: H. Huerga reports grants from Unitaid, during the conduct of the study. Conflict of interest: S. Atwood has nothing to disclose. Conflict of interest: S. Ahmed reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen Pharmaceutical, outside the submitted work. Conflict of interest: M. Khan has nothing to disclose. Conflict of interest: T. Sultana has nothing to disclose. Conflict of interest: M. Manzur-ul-Alam has nothing to disclose. Conflict of interest: L.N.Q. Vo reports grants and non-financial support (drugs/equipment) from Unitaid via IRD Global during the conduct of the study. Conflict of interest: L. Lecca has nothing to disclose. Conflict of interest: K. Yae has nothing to disclose. Conflict of interest: S. Kozhabekov has nothing to disclose. Conflict of interest: M. Tamirat has nothing to disclose. Conflict of interest: A. Gelin has nothing to disclose. Conflict of interest: S.C. Vilbrun has nothing to disclose. Conflict of interest: M. Kikvidze has nothing to disclose. Conflict of interest: J. Faqirzai has nothing to disclose. Conflict of interest: A. Kadyrov has nothing to disclose. Conflict of interest: A. Skrahina has nothing to disclose. Conflict of interest: A. Mesic has nothing to disclose. Conflict of interest: N. Avagyan has nothing to disclose. Conflict of interest: M. Bastard reports grants from Unitaid, during the conduct of the study. Conflict of interest: M.L. Rich reports grants from Unitaid, during the conduct of the study; personal fees for consultancy from World Health Organization, other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: U. Khan reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: C.D. Mitnick reports a grant from Unitaid to fund the study and that the endTB Consortium coordinated donations of delamanid (Otsuka Pharmaceutical) and bedaquiline (Janssen) to be used for treatment by some of the patients included in the endTB Observational Study., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

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.

We examined Mycobacterium tuberculosis DNA detection from buccal swab samples collected from children in Lima, Peru. DNA was extracted and amplified via real-time polymerase chain reaction. Sensitivity was 21% (95% confidence interval [CI]: 7%-42%) in 24 culture-confirmed tuberculosis cases and 4.6% (95% CI: 1%-13%) in 65 clinically diagnosed unconfirmed cases. Sensitivity was highest for smear-positive tuberculosis. Specificity was 99% in the 199 controls (95% CI: 96%-100%).

We quantified longitudinal changes in CD4 T-cell count, viral load suppression and combined antiretroviral therapy adherence from childhood to adolescence among patients living with HIV in urban Peru. Mean CD4 count and viral load suppression decreased dramatically in early adolescence (13 years of age) in tandem with increases in nonadherence.

Background: Stool is a promising specimen option to diagnose pediatric tuberculosis (TB), but studies have reported a wide range of test sensitivities. We conducted a meta-analysis to assess the accuracy of Xpert MTB/RIF or 'in-house' molecular tests on stool samples against culture or Xpert MTB/RIF on respiratory samples or clinically-diagnosed unconfirmed TB and aimed to identify factors that contribute to the heterogeneity of reported sensitivity., Methods: We searched EMBASE and Pubmed databases and conference abstract books for studies reporting molecular stool testing against a clinical or microbiological reference standard among children., Results: We identified 16 studies that included 2,481 children in stool test analyses. Pooled specificity was 98% [95%CI: 96-99], pooled sensitivity was 57% [95%CI: 40-72] against culture and 3% [95%CI: 2-6] among children with clinically-diagnosed, unconfirmed TB. There was much heterogeneity. Sensitivity was higher among children with a smear-positive sputum test. Rifampin resistance in stool was reported in two studies and detected in 5/14 children (36%)., Conclusion: Our results suggest molecular stool tests have potential as diagnostic rule-in tests, but it is challenging to optimize sensitivity due to between-study variation in methodology and test procedures. Therefore, we recommend future research with rigorous study design and standardized results reporting., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The global HIV burden among adolescents ages 10-19 is growing. This population concurrently confronts the multifaceted challenges of adolescence and living with HIV. With the goal of informing future interventions tailored to this group, we assessed sexual activity, HIV diagnosis disclosure, combination antiretroviral therapy (cART) adherence, and drug use among adolescents living with HIV (ALHIV) in Lima, Peru., Methods: Adolescents at risk or with a history of suboptimal cART adherence completed a self-administered, health behaviors survey and participated in support group sessions, which were audio recorded and used as a qualitative data source. Additionally, we conducted in-depth interviews with caregivers and care providers of ALHIV. Thematic content analysis was performed on the group transcripts and in-depth interviews and integrated with data from the survey to describe adolescents' health related behaviors., Results: We enrolled 34 ALHIV, of which 32 (14 male, 18 female, median age 14.5 years) completed the health behavior survey. Nine (28%) adolescents reported prior sexual intercourse, a minority of whom (44%) reported using a condom. cART adherence was highest in the 10-12 age group with 89% reporting ≤2 missed doses in the last month, compared to 36% in adolescents 13 years or older. Over 80% of adolescents had never disclosed their HIV status to a friend or romantic partner. Adolescents, caregivers, and health service providers described sexual health misinformation and difficulty having conversations about sexual health and HIV., Conclusions: In this group of ALHIV, adherence to cART declined with age and condom use among sexually active adolescents was low. Multifactorial interventions addressing sexual health, gaps in HIV-related knowledge, and management of disclosure and romantic relationships are urgently needed for this population.

Background: No study of long-term protection following killed oral cholera vaccination has been done outside of the historically cholera-endemic areas of south Asia, or has examined protection after a single-dose vaccination regimen. To address this, we examined the duration of protection of the standard two-dose regimen and an incomplete regimen of one dose up to 4 years after vaccination in Haiti., Methods: In the setting of two-dose vaccination campaigns with a killed, bivalent, whole-cell oral cholera vaccination, we did a case-control study from October, 2012 through November, 2016. Eligible participants were required to be resident in the vaccine catchment area (Artibonite Department or Central Department) where they were recruited at the start of the study; and be eligible for the vaccination campaign (ie, aged ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign). Patients with cholera had a positive stool culture and were recruited from cholera treatment centres. Community controls were matched to people with cholera by age group, time, and neighbourhood. We did adjusted matched regression analyses to calculate vaccine effectiveness and examine heterogeneity in effectiveness over time. The primary outcome was the effectiveness of one and two oral cholera doses as compared with zero doses from 2 months to 48 months after vaccination, measured by self reporting., Findings: Among 178 people assigned to the case group and 706 people assigned to the control group, we found no evidence that two-dose effectiveness decreased during follow-up. In adjusted analyses, the average cumulative 4 year effectiveness for two doses was 76% (95% CI 59-86). In contrast, single-dose effectiveness decreased over time in a log-linear fashion, with a predicted vaccine effectiveness of 79% at the end of 12 months (95% CI 43-93), which declined to zero before the end of the second year., Interpretation: In a setting of epidemic and newly endemic cholera in Haiti, single-dose vaccination with killed, bivalent, whole-cell oral cholera vaccination provided short-term protection; however, vaccination with two doses was required for long-term protection, which lasted up to 4 years after vaccination. These results add to the evidence in support of the use of killed, bivalent, whole-cell oral cholera vaccination as part of comprehensive cholera control plans., Funding: US National Institute of Allergy and Infectious Diseases of the National Institutes of Health and the Bill & Melinda Gates Foundation., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Molecular diagnostics that rapidly and accurately predict fluoroquinolone (FQ) resistance promise to improve treatment outcomes for individuals with multidrug-resistant (MDR) tuberculosis (TB). Mutations in the gyr genes, though, can cause variable levels of in vitro FQ resistance, and some in vitro resistance remains unexplained by gyr mutations alone, but the implications of these discrepancies for treatment outcome are unknown., Methods: We performed a retrospective cohort study of 172 subjects with MDR/extensively drug-resistant TB subjects and sequenced the full gyrA and gyrB open reading frames in their respective sputum TB isolates. The gyr mutations were classified into 2 categories: a set of mutations that encode high-level FQ resistance and a second set that encodes intermediate resistance levels. We constructed a Cox proportional model to assess the effect of the gyr mutation type on the time to death or treatment failure and compared this with in vitro FQ resistance, controlling for host and treatment factors., Results: Controlling for other host and treatment factors and compared with patients with isolates without gyr resistance mutations, "high-level" gyr mutations significantly predict poor treatment outcomes with a hazard ratio of 2.6 (1.2-5.6). We observed a hazard of death and treatment failure with "intermediate-level" gyr mutations of 1.3 (0.6-3.1), which did not reach statistical significance. The gyr mutations were not different than culture-based FQ drug susceptibility testing in predicting the hazard of death or treatment failure and may be superior., Conclusions: FQ molecular-based diagnostic tests may better predict treatment response than traditional drug susceptibility testing and open avenues for personalizing TB therapy., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Case-control studies to quantify oral cholera vaccine effectiveness (VE) often rely on neighbors without diarrhea as community controls. Test-negative controls can be easily recruited and may minimize bias due to differential health-seeking behavior and recall. We compared VE estimates derived from community and test-negative controls and conducted bias-indicator analyses to assess potential bias with community controls., Methods: From October 2012 through November 2016, patients with acute watery diarrhea were recruited from cholera treatment centers in rural Haiti. Cholera cases had a positive stool culture. Non-cholera diarrhea cases (test-negative controls and non-cholera diarrhea cases for bias-indicator analyses) had a negative culture and rapid test. Up to four community controls were matched to diarrhea cases by age group, time, and neighborhood., Results: Primary analyses included 181 cholera cases, 157 non-cholera diarrhea cases, 716 VE community controls and 625 bias-indicator community controls. VE for self-reported vaccination with two doses was consistent across the two control groups, with statistically significant VE estimates ranging from 72 to 74%. Sensitivity analyses revealed similar, though somewhat attenuated estimates for self-reported two dose VE. Bias-indicator estimates were consistently less than one, with VE estimates ranging from 19 to 43%, some of which were statistically significant., Conclusions: OCV estimates from case-control analyses using community and test-negative controls were similar. While bias-indicator analyses suggested possible over-estimation of VE estimates using community controls, test-negative analyses suggested this bias, if present, was minimal. Test-negative controls can be a valid low-cost and time-efficient alternative to community controls for OCV effectiveness estimation and may be especially relevant in emergency situations., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Low and deficient levels of vitamin A are common in low- and middle-income countries where tuberculosis burden is high. We assessed the impact of baseline levels of vitamin A and carotenoids on tuberculosis disease risk., Methods: We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary tuberculosis case patients in Lima, Peru. We defined case patients as human immunodeficiency virus (HIV)-negative HHCs with blood samples in whom tuberculosis disease developed ≥15 days after enrollment of the index patient. For each case patient, we randomly selected 4 controls from among contacts in whom tuberculosis disease did not develop, matching for sex and year of age. We used conditional logistic regression to estimate odds ratios for incident tuberculosis disease by vitamin A and carotenoids levels, controlling for other nutritional and socioeconomic factors., Results: Among 6751 HIV-negative HHCs with baseline blood samples, 192 had secondary tuberculosis disease during follow-up. We analyzed 180 case patients with viable samples and 709 matched controls. After controlling for possible confounders, we found that baseline vitamin A deficiency was associated with a 10-fold increase in risk of tuberculosis disease among HHCs (adjusted odds ratio, 10.53; 95% confidence interval, 3.73-29.70; P < .001). This association was dose dependent, with stepwise increases in tuberculosis disease risk with each decreasing quartile of vitamin A level., Conclusions: Vitamin A deficiency strongly predicted the risk of incident tuberculosis disease among HHCs of patients with tuberculosis. Vitamin A supplementation among individuals at high risk of tuberculosis may provide an effective means of preventing tuberculosis disease., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Food rations are increasingly offered as part of HIV programs in resource-poor settings, often targeted solely to those with under-nutrition by low body mass index (BMI). This practice does not consider food insecurity, another important risk factor for poor outcomes in people living with HIV/AIDS (PLWH). We analyzed factors associated with low BMI and severe food insecurity in 523 PLWH receiving antiretroviral therapy in rural Haiti using logistic regression. Food insecurity was present in 89 % of individuals. Among those with severe food insecurity, 86 % had a BMI ≥ 18.5 kg/m(2). Severe food insecurity was associated with illiteracy [adjusted odds ratio (AOR) 1.79, p = 0.005], having no income (AOR 1.58, p = 0.04), and poverty (p < 0.001). Compared with those with little to no food insecurity, individuals with severe food insecurity had a less diverse diet. We found that food insecurity was highly prevalent in PLWH receiving antiretroviral therapy in rural Haiti. Using BMI as a sole criterion for food supplementation in HIV programs can exclude highly vulnerable individuals who may benefit from such support.

Clinical, socioeconomic, and access barriers remain a critical problem to antiretroviral (ART) programs in sub-Saharan Africa. Community-based accompaniment (CBA), including daily home visits and psychosocial and socioeconomic support, has been associated with improved patient outcomes at 1 year. We conducted a prospective observational cohort study of 578 HIV-infected adults initiating ART in 2007-2008 with or without CBA in rural Rwanda. Among patients without CBA, those with advanced HIV disease, low CD4 cell counts, lower social support, and transport costs had significantly higher odds of negative outcomes at 1 year; amongst patients who received CBA, only those with low CD4 cell counts had significantly higher odds of negative outcomes at 1 year. CBA also significantly mitigated the effect of transport costs and inaccessibility of services on the likelihood of negative outcome. CBA may be one approach to mitigating known risk factors for negative outcomes for patients on ART in resource-poor settings.

Background: Between April and June, 2012, a reactive cholera vaccination campaign was done in Haiti with an oral inactivated bivalent whole-cell vaccine. We aimed to assess the effectiveness of the vaccine in a case-control study and to assess the likelihood of bias in that study in a bias-indicator study., Methods: Residents of Bocozel or Grand Saline who were eligible for the vaccination campaign (ie, age ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign) were included. In the primary case-control study, cases had acute watery diarrhoea, sought treatment at one of three participating cholera treatment units, and had a stool sample positive for cholera by culture. For each case, four control individuals who did not seek treatment for acute watery diarrhoea were matched by location of residence, enrolment time (within 2 weeks of the case), and age (1-4 years, 5-15 years, and >15 years). Cases in the bias-indicator study were individuals with acute watery diarrhoea with a negative stool sample for cholera. Controls were selected in the same manner as in the primary case-control study. Trained staff used standard laboratory procedures to do rapid tests and stool cultures from study cases. Participants were interviewed to collect data on sociodemographic characteristics, risk factors for cholera, and self-reported vaccination. Data were analysed by conditional logistic regression, adjusting for matching factors., Findings: From Oct 24, 2012, to March 9, 2014, 114 eligible individuals presented with acute watery diarrhoea and were enrolled, 25 of whom were subsequently excluded. 47 participants were analysed as cases in the vaccine effectiveness case-control study and 42 as cases in the bias-indicator study. 33 (70%) of 47 cholera cases self-reported vaccination versus 167 (89%) of 188 controls (vaccine effectiveness 63%, 95% CI 8-85). 27 (57%) of 47 cases had certified vaccination versus 147 (78%) of 188 controls (vaccine effectiveness 58%, 13-80). Neither self-reported nor verified vaccination was significantly associated with non-cholera diarrhoea (vaccine effectiveness 18%, 95% CI -208 to 78 by self-report and -21%, -238 to 57 by verified vaccination)., Interpretation: Bivalent whole-cell oral cholera vaccine effectively protected against cholera in Haiti from 4 months to 24 months after vaccination. Vaccination is an important component of efforts to control cholera epidemics., Funding: National Institutes of Health, Delivering Oral Vaccines Effectively project, and Department of Global Health and Social Medicine at Harvard Medical School., (Copyright © 2015 Ivers et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.)

Background: Haiti's cholera epidemic has been devastating partly due to underlying weak infrastructure and limited clean water and sanitation. A comprehensive approach to cholera control is crucial, yet some have argued that oral cholera vaccination (OCV) might result in reduced hygiene practice among recipients. We evaluated the impact of an OCV campaign on knowledge and health practice in rural Haiti., Methodology/principal Findings: We administered baseline surveys on knowledge and practice relevant to cholera and waterborne disease to every 10th household during a census in rural Haiti in February 2012 (N = 811). An OCV campaign occurred from May-June 2012 after which we administered identical surveys to 518 households randomly chosen from the same region in September 2012. We compared responses pre- and post-OCV campaign. Post-vaccination, there was improved knowledge with significant increase in percentage of respondents with ≥ 3 correct responses on cholera transmission mechanisms (odds ratio[OR] 1.91; 95% confidence interval[CI] 1.52-2.40), preventive methods (OR 1.83; 95% CI 1.46-2.30), and water treatment modalities (OR 2.75; 95% CI 2.16-3.50). Relative to pre-vaccination, participants were more likely post-OCV to report always treating water (OR 1.62; 95% CI 1.28-2.05). Respondents were also more likely to report hand washing with soap and water >4 times daily post-vaccine (OR 1.30; 95% CI 1.03-1.64). Knowledge of treating water as a cholera prevention measure was associated with practice of always treating water (OR 1.47; 95% CI 1.14-1.89). Post-vaccination, knowledge was associated with frequent hand washing (OR 2.47; 95% CI 1.35-4.51)., Conclusion: An OCV campaign in rural Haiti was associated with significant improvement in cholera knowledge and practices related to waterborne disease. OCV can be part of comprehensive cholera control and reinforce, not detract from, other control efforts in Haiti.

Background: Minimizing death and ensuring high retention and good adherence remain ongoing challenges for human immunodeficiency virus (HIV) treatment programs. We examined whether the addition of community-based accompaniment (characterized by daily home visits from a community health worker, directly observed treatment, nutritional support, transportation stipends, and other support as needed) to the Rwanda national model for antiretroviral therapy (ART) delivery would improve retention in care, viral load suppression, and change in CD4 count, relative to the national model alone., Methods: We conducted a prospective observational cohort study among 610 HIV-infected adults initiating ART in 1 of 2 programs in rural Rwanda. Psychosocial and clinical characteristics were recorded at ART initiation. Death, treatment retention, and plasma viral load were assessed at 1 year. CD4 count was evaluated at 6-month intervals. Multivariable regression models were used to adjust for baseline differences between the 2 populations., Results: Eighty-five percent and 79% of participants in the community-based and clinic-based programs, respectively, were retained with viral load suppression at 1 year. After adjusting for CD4 count, depression, physical health quality of life, and food insecurity, community-based accompaniment was protective against death or loss to follow-up during the first year of ART (hazard ratio, 0.17; 95% confidence interval [CI], .09-.35; P < .0001). In a second multivariable analysis, individuals receiving accompaniment were more likely to be retained with a suppressed viral load at 1 year (risk ratio: 1.15; 95% CI, 1.03-1.27; P = .01)., Conclusions: These findings indicate that community-based accompaniment is effective in improving retention, when added to a clinic-based program with fewer patient support mechanisms.

Background: Mobile health (mHealth) technologies provide many potential benefits to the delivery of health care. Medical decision support tools have shown particular promise in improving quality of care and provider workflow. Frontline health workers such as Community Health Workers (CHWs) have been shown to be effective in extending the reach of care, yet only a few medicine dosing tools are available to them., Objective: We developed an mHealth medicine dosing tool tailored to the skill level of CHWs to assist in the delivery of care. The mHealth tool was created for CHWs with primary school education working in rural Mexico and Guatemala. Perceptions and impressions of this tool were collected and compared to an existing paper-based medicine dosing tool., Methods: Seventeen Partners In Health CHWs in rural Mexico and Guatemala completed a one-day training in the mHealth medicine dosing tool. Following the training, a prescription dosing test was administered, and CHWs were given the choice to use the mHealth or paper-based tool to answer 7 questions. Subsequently, demographic and qualitative data was collected using a questionnaire and an in-person interview conducted in Spanish, then translated into English. The qualitative questions captured data on 4 categories: comfort, acceptability, preference, and accuracy. Qualitative responses were analyzed for major themes and quantitative variables were analyzed using SAS., Results: 82% of the 17 CHWs chose the mHealth tool for at least 1 of 7 questions compared to 53% (9/17) who chose to use the paper-based tool. 93% (13/14) rated the phone as being easy or very easy to use, and 56% (5/9) who used the paper-based tool rated it as easy or very easy. Dosing accuracy was generally higher among questions answered using the mHealth tool relative to questions answered using the paper-based tool. Analysis of major qualitative themes indicated that the mHealth tool was perceived as being quick, easy to use, and as having complete information. The mHealth tool was seen as an acceptable dosing tool to use and as a way for CHWs to gain credibility within the community., Conclusions: A tailored cell phone-based mHealth medicine dosing tool was found to be useful and acceptable by CHWs in rural Mexico and Guatemala. The streamlined workflow of the mHealth tool and benefits such as the speed and self-lighting were found to be particularly useful features. Well designed and positioned tools such as this may improve effective task shifting by reinforcing the tasks that different cadres of workers are asked to perform. Further studies can explore how to best implement this mHealth tool in real-world settings, including how to incorporate the best elements of the paper-based tool that were also found to be helpful.

Background: Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy., Methods: We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis., Results: Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2-53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17-0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17-50.60]; P = .004)., Conclusions: Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease.

Background: Malaria control is currently receiving significant international commitment. As part of this commitment, Rwanda has undertaken a two-pronged approach to combating malaria via mass distribution of long-lasting insecticidal-treated nets and distribution of antimalarial medications by community health workers. This study attempted to measure the impact of these interventions on paediatric hospitalizations for malaria and on laboratory markers of disease severity., Methods: A retrospective analysis of hospital records pre- and post-community-based malaria control interventions at a district hospital in rural Rwanda was performed. The interventions took place in August 2006 in the region served by the hospital and consisted of mass insecticide treated net distribution and community health workers antimalarial medication disbursement. The study periods consisted of the December-February high transmission seasons pre- and post-rollout. The record review examined a total of 551 paediatric admissions to identify 1) laboratory-confirmed malaria, defined by thick smear examination, 2) suspected malaria, defined as fever and symptoms consistent with malaria in the absence of an alternate cause, and 3) all-cause admissions. To define the impact of the intervention on clinical markers of malaria disease, trends in admission peripheral parasitaemia and haemoglobin were analyzed. To define accuracy of clinical diagnoses, trends in proportions of malaria admissions which were microscopy-confirmed before and after the intervention were examined. Finally, to assess overall management of febrile illnesses antibiotic use was described., Results: Of the 551 total admissions, 268 (48.6%) and 437 (79.3%) were attributable to laboratory confirmed and suspected malaria, respectively. The absolute number of admissions due to suspected malaria was smaller during the post-intervention period (N = 150) relative to the pre-intervention period (N = 287), in spite of an increase in the absolute number of hospitalizations due to other causes during the post-intervention period. The percentage of suspected malaria admissions that were laboratory-confirmed was greater during the pre-intervention period (80.4%) relative to the post-intervention period (48.1%, prevalence ratio [PR]: 1.67; 95% CI: 1.39-2.02; chi-squared p-value < 0.0001). Among children admitted with laboratory-confirmed malaria, the risk of high parasitaemia was higher during the pre-intervention period relative to the post-intervention period (age-adjusted PR: 1.62; 95% CI: 1.11-2.38; chi-squared p-value = 0.004), and the risk of severe anaemia was more than twofold greater during the prei-ntervention period (age-adjusted PR: 2.47; 95% CI: 0.84-7.24; chi-squared p-value = 0.08). Antibiotic use was common, with 70.7% of all children with clinical malaria and 86.4% of children with slide-negative malaria receiving antibacterial therapy., Conclusion: This study suggests that both admissions for malaria and laboratory markers of clinical disease among children may be rapidly reduced following community-based malaria control efforts. Additionally, this study highlights the problem of over-diagnosis and over-treatment of malaria in malaria-endemic regions, especially as malaria prevalence falls. More accurate diagnosis and management of febrile illnesses is critically needed both now and as fever aetiologies change with further reductions in malaria.