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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. Author summary: Food insecurity has been found to be a risk factor for cholera at the household and national level, 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 reported history of severe, medically-attended cholera. The association was dose-dependent, with the odds of reported cholera increasing linearly with household food insecurity. Household food insecurity was 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 of 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 practices may be one causal pathway by which food insecurity increases risk of developing cholera. In this study, we provide a framework for future longitudinal and qualitative studies to investigate whether interventions that target food insecurity could also reduce cholera risk among populations who face a high burden of both conditions. [ABSTRACT FROM AUTHOR]

Diarrheal illness is a major cause of morbidity and mortality among children in Haiti, and the impact of diarrheal illness was compounded by a cholera outbreak between 2010 and 2019. Our understanding of risk factors for diarrhea among children during this outbreak is limited. We conducted a secondary analysis of data collected as part of a cholera vaccine effectiveness study to identify factors associated with medically attended diarrhea among children in central Haiti from October of 2012 through November of 2016. We identified 47 children aged one to five years old who presented to medical clinics with acute, watery diarrhea, and 166 matched controls who did not have diarrhea, and we performed conditional logistic regression to identify factors associated with diarrhea. Discontinuing exclusive breastfeeding within one month of birth was associated with increased risk of diarrhea (RR 6.9, 95% CI 1.46–32.64), and diarrhea was inversely associated with reported history of supplementation with vitamin A (RR 0.05, 95% CI 0.004–0.56) and zinc (reported among 0% of cases vs. 17% of controls). Because of the concordance in supplementation patterns, it was not possible to attribute the association to vitamin A or zinc independently. While having a respondent who correctly identified ≥3 means of avoiding cholera was associated with reduced risk of diarrhea (RR 0.43, 95% CI 0.19–1.01), reported household sanitation practices and knowledge of cholera were not consistently associated with risk of diarrhea. These findings support ongoing efforts to reduce barriers to breastfeeding and promote pediatric supplementation with vitamin A and zinc in Haiti. Given the reduced efficacy of current oral cholera vaccines (OCV) among children, the results reinforce the importance of breastfeeding and micronutrient supplementation in preventing all-cause pediatric diarrheal illness generally and during cholera outbreaks. Author summary: Diarrheal diseases are leading causes of illness and death among children throughout the world, and children in Haiti were particularly impacted by diarrhea during the cholera outbreak that started in 2010. Between 2012 and 2016, data were collected as part of a case-control study of oral cholera vaccine (OCV) effectiveness in Haiti. We analyzed data from that study to identify factors associated with diarrheal illness, including cholera and non-cholera diarrhea, among children ages one through five years old. We found a direct association between longer duration of exclusive breastfeeding and supplementation with vitamin A and zinc and a reduced risk of diarrhea. These findings shed light on potentially important components of efforts to reduce pediatric diarrheal illness in Haiti generally, and to reduce pediatric diarrhea in the context of cholera outbreaks in Haiti and elsewhere. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST). Methods and findings: The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (−0.06; 95% UI: [−0.49, 0.032] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova's national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics. Conclusions: Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels. Author summary: Why was this study done?: Drug resistance poses a major barrier to the effective treatment of tuberculosis, especially in Moldova and other post-Soviet states which have the highest levels of resistance in the world. Individuals with tuberculosis resistant to the key drug rifampicin face a worse prognosis, a longer and more expensive course of treatment, and more side effects than individuals with rifampicin-susceptible tuberculosis. Until recently, the standard of care for rifampicin-resistant tuberculosis (RR-TB) involved many drugs in combination, often given for 18 months or longer. The newer, 6-month "BPaLM" regimen is comprised of 4 drugs (bedaquiline, pretomanid, linezolid, and moxifloxacin) to which resistance levels are currently low, and while it was shown to be just as effective as the standard of care when health outcomes were measured at 72 weeks from treatment initiation, its effect on lifetime health outcomes, costs, and the acquisition of drug resistance was less clear. What did the researchers do and find?: Using a mathematical model, we projected the lifetime health benefits and costs of the 6-month BPaLM regimen as compared to 9–18 month, standard of care treatments for RR-TB, and found that 6 months of BPaLM would be likely to provide similar health benefits, at lower cost. Compared to the standard of care, we also found that the 6-month BPaLM regimen could shorten the average duration of tuberculosis resistant to the drugs amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it may increase the average duration of tuberculosis resistant to delamanid and pretomanid. For individuals receiving BPaLM who had to stop taking the drug moxifloxacin, we found that it would likely be beneficial on both health and cost grounds to replace it with clofazimine, thereby topping the regimen back up to 4 drugs. What do these findings mean?: Using conventional benchmarks for value-for-money, we estimated that 6 months of BPaLM would be a cost-effective approach for the treatment of RR-TB in Moldova, and potentially other post-Soviet countries. Though the impact of the 6-month BPaLM regimen on the spread of drug resistance is uncertain and not addressed directly by this study, this combination of newer drugs appears to achieve cure more quickly, thereby reducing the amount of time an individual is potentially infectious. This may be beneficial in fighting resistance to several drugs, even while it may increase the spread of resistance to others. Further studies may be warranted to explore how well these findings would translate to different global regions where health system capabilities, costs, and existing resistance patterns may differ. [ABSTRACT FROM AUTHOR]

• The World Health Organization recommends the use of oral cholera vaccines in cholera control efforts. • We conducted a case-control study of the cholera vaccine, Euvichol® in Haiti. • Two-dose Euvichol® vaccine effectiveness was 69%. • Euvichol® can serve as one component of comprehensive cholera control efforts. The World Health Organization recommends the use of oral cholera vaccine (OCV) in cholera control efforts. Euvichol®, pre-qualified in 2015, is the leading component of the Global OCV stockpile, but data on its field effectiveness are limited. To evaluate Euvichol® vaccine effectiveness (VE), we conducted a case-control study between September 2018 to March 2020 following an OCV campaign in November 2017 in Haiti. Cases were individuals with acute watery diarrhea. Stool samples were tested by culture and real-time polymerase chain reaction of the Vibrio cholerae ctxA gene. Cases were matched to four community controls without diarrhea by residence, enrollment time, age, and gender, and interviewed for sociodemographics, risk factors, and self-reported vaccination. Cholera cases were analyzed by conditional logistic regression in the VE study. Non-cholera diarrhea cases were analyzed in a bias-indicator study. We enrolled 15 cholera cases matched to 60 controls, and 63 non-cholera diarrhea cases matched to 249 controls. In the VE analysis, eight (53%) cases reported vaccination with any number of doses compared to 43 (72%) controls. Adjusted two-dose OCV VE was 69% (95% CI –71 to 94%). Between 10-27 months after vaccination, Euvichol® was effective and similar to Shanchol™, suggesting that it can serve as one component of multi-sectoral comprehensive cholera control. [ABSTRACT FROM AUTHOR]

In Haiti in 2017, the prevalence of serum vibriocidal antibody titers against Vibrio cholerae serogroup O1 among adults was 12.4% in Cerca-la-Source and 9.54% in Mirebalais, suggesting a high recent prevalence of infection. Improved surveillance programs to monitor cholera and guide public health interventions in Haiti are necessary. [ABSTRACT FROM AUTHOR]

Background Few studies have examined the burden of postacute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in low- and middle-income countries. We sought to characterize PASC with self-reported questionnaires and clinical examinations of end-organ function in Lima, Peru. Methods From January to July 2021, we recruited participants at least 8 weeks after COVID-19 diagnosis from a case registry in Lima, Peru. We evaluated participants for PASC with questionnaires, neuropsychiatric evaluations, chest X-ray, spirometry, electrocardiogram, and echocardiogram. We used multivariable models to identify risk factors for PASC. Results We assessed 989 participants for PASC at a median 4.7 months after diagnosis. Clinically significant respiratory symptoms were reported by 68.3% of participants, particularly those who had been severely ill during acute COVID-19, and were associated with cardiac findings of ventricular hypertrophy or dilation on echocardiogram. Neuropsychiatric questionnaires were consistent with depression in 20.7% and cognitive impairment in 8.0%. Female sex and older age were associated with increased risk of respiratory (adjusted odds ratio [aOR], 2.36 [95% confidence interval {CI}, 1.69–3.31] and aOR, 1.01 [95% CI, 1.00–1.03], respectively) and neuropsychiatric sequelae (aOR, 2.99 [95% CI, 2.16–4.18] and aOR, 1.02 [95% CI, 1.01–1.03], respectively). Conclusions COVID-19 survivors in Lima, Peru, experienced frequent postacute respiratory symptoms and depression, particularly among older and female participants. Clinical examinations highlighted the need for cardiopulmonary rehabilitation among persons with severe COVID-19; psychosocial support may be required among all COVID-19 survivors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We report on the sensitivity and specificity of stool culture compared to polymerase chain reaction for detecting Vibrio cholerae in Haiti during the waning period of the initial outbreak in 2018–2019. We found that stool culture (with a sensitivity of 33.3% and specificity of 97.4%) may not be sufficiently robust in this context. [ABSTRACT FROM AUTHOR]

Introduction: Adolescents living with HIV (ALWH) experience higher mortality rates compared to other age groups, exacerbated by the suboptimal transition from paediatric to adult HIV care, during which decreased adherence to antiretroviral therapy (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. Methods: PASEO consisted of six core elements designed to support ALWH during and after the transition to adult HIV care. During 2019–2021, 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 analysed using a framework analysis approach and emergent themes were summarized with illustrative quotes. Results: We conducted five focus groups and 11 in‐depth interviews among N = 26 ALWH and nine key‐informant interviews with HIV care personnel. ALWH participants included males, females and one transgender female, and those with both early childhood and recent HIV infection. 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 for PASEO. Both ALWH and HIV professionals expressed hope that PASEO would be scaled. HIV professionals voiced concerns regarding financing PASEO in the future. Conclusions: A multicomponent CBA intervention to increase ART adherence among ALWH in Peru was highly acceptable by ALWH and HIV programme personnel. Future research should determine the efficacy and economic impact of the intervention. [ABSTRACT FROM AUTHOR]

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 NCT02754765. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]