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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. [ABSTRACT FROM AUTHOR]

We found that comprehensive, integrated, community-based intervention (characterized by daily home visits from a community health worker, directly observed treatment, nutritional support, and transportation stipends) was associated with higher antiretroviral therapy retention at 1 year among adults in rural Rwanda.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. [ABSTRACT FROM AUTHOR]

In an extensively previously treated patient population, receipt of an aggressive regimen (ie, one containing ≥5 likely effective drugs, including a fluoroquinolone and injectable) for ≥18 months following sputum conversion, was associated with a reduced risk of recurrence.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. [ABSTRACT FROM PUBLISHER]

Background. Completing treatment for multidrug-resistant (MDR) tuberculosis (TB) may be more challenging than completing first-line TB therapy, especially in resource-poor settings. The objectives of this study were to (1) identify risk factors for default from MDR TB therapy (defined as prolonged treatment interruption), (2) quantify mortality among patients who default from treatment, and (3) identify risk factors for death after default from treatment. Methods. We performed a retrospective chart review to identify risk factors for default from MDR TB therapy and conducted home visits to assess mortality among patients who defaulted from such therapy. Results. Sixty-seven (10.0%) of 671 patients defaulted from MDR TB therapy. The median time to treatment default was 438 days (interquartile range, 152–710 days), and 27 (40.3%) of the 67 patients who defaulted from treatment had culture-positive sputum at the time of default. Substance use (hazard ratio, 2.96; 95% confidence interval, 1.56–5.62; P =.001), substandard housing conditions (hazard ratio, 1.83; 95% confidence interval, 1.07-3.11; P =.03), later year of enrollment (hazard ratio, 1.62, 95% confidence interval, 1.09–2.41; P =.02), and health district (P =.02) predicted default from therapy in a multivariable analysis. Severe adverse events did not predict default from therapy. Forty-seven (70.1%) of 67 patients who defaulted from therapy were successfully traced; of these, 25 (53.2%) had died. Poor bacteriologic response, <1 year of treatment at the time of default, low education level, and diagnosis with a psychiatric disorder significantly predicted death after default in a multivariable analysis. Conclusions. The proportion of patients who defaulted from MDR TB treatment was relatively low. The large proportion of patients who had culture-positive sputum at the time of treatment default underscores the public health importance of minimizing treatment default. Prognosis for patients who defaulted from therapy was poor. Interventions aimed at preventing treatment default may reduce TB-related mortality. [ABSTRACT FROM AUTHOR]

Delamanid should be effective against highly resistant strains of Mycobacterium tuberculosis , but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months. Clinical Trials Registration. NCT02754765. [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]

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. [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]

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]

Background. We sought to determine whether treatment with a "long aggressive regimen" was associated with lower rates of relapse among patients successfully treated for pulmonary multidrug-resistant tuberculosis (MDR-TB) in Tomsk, Russia. Methods. We conducted a retrospective cohort study of adult patients that initiated MDR-TB treatment with individualized regimens between September 2000 and November 2004, and were successfully treated. Patients were classified as having received "aggressive regimens" if their intensive phase consisted of at least 5 likely effective drugs (including a second-line injectable and a fluoroquinolone) used for at least 6 months post culture conversion, and their continuation phase included at least 4 likely effective drugs. Patients that were treated with aggressive regimens for a minimum duration of 18 months post culture conversion were classified as having received "long aggressive regimens." We used recurrence as a proxy for relapse because genotyping was not performed. After treatment, patients were classified as having disease recurrence if cultures grew MDR-TB or they re-initiated MDR-TB therapy. Data were analyzed using Cox proportional hazard regression. Results. Of 408 successfully treated patients, 399 (97.5%) with at least 1 follow-up visit were included. Median duration of follow-up was 42.4 months (interquartile range: 20.5-59.5), and there were 27 recurrence episodes. In a multivariable complete case analysis (n = 371 [92.9%]) adjusting for potential confounders, long aggressive regimens were associated with a lower rate of recurrence (adjusted hazard ratio: 0.22, 95% confidence interval, .05-.92). Conclusions. Long aggressive regimens for MDR-TB treatment are associated with lower risk of disease recurrence. [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]

We followed 35 children meeting a research definition for unconfirmed tuberculosis (TB) but in whom a pediatric pulmonologist did not diagnose or treat TB. After a median follow-up of 16.4 months, most children were not diagnosed with TB following a comprehensive evaluation. However, 2 were diagnosed with TB, demonstrating high TB risk (6%; exact 95% CI, 1%–19%). In some contexts, researchers may wish to supplement these research definitions with clinical decision data and longitudinal follow-up in order to improve specificity. [ABSTRACT FROM AUTHOR]

We estimated the proportion of recurrence within 2 years among adults cured by individualized multidrug-resistant tuberculosis regimens in Peru. Among 310 individuals with at least 24 months of follow-up, 16 experienced an episode of recurrent tuberculosis. If we assume the worst for treatment effectiveness—that all 16 episodes were caused by the original tuberculosis strain—then 5.2% (95% confidence interval, 3.0%-8.2%) experienced true relapse. This is an upper-bound estimate of relapse on which new regimens must improve. [ABSTRACT FROM AUTHOR]

We evaluated immune responses following bivalent oral cholera vaccination (Shanchol [Shantha Biotechnics]; BivWC) in a cohort of 25 human immunodeficiency virus (HIV)-infected adults in Haiti. Compared with adults without HIV infection, vaccination in HIV-infected individuals resulted in lower vibriocidal responses against Vibrio cholerae O1, and there was a positive relationship between the CD4+ T-cell count and vibriocidal responses following vaccination. Nevertheless, seroconversion occurred at a rate of 65% against the Ogawa serotype and 74% against the Inaba serotype in adults with HIV infection. These results suggest that the vaccine retains substantial immunogenicity in adults with HIV infection and may benefit this population by protecting against cholera. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study of patients treated for multidrug-resistant tuberculosis in the Russian Federation, we found that monthly exposure to an aggressive multidrug-resistant tuberculosis regimen was a robust predictor of decreased risk of death or failure during treatment.Background. Evidence is sparse regarding the optimal construction of regimens to treat multidrug-resistant (MDR) tuberculosis disease due to strains of Mycobacterium tuberculosis resistant to at least both isoniazid and rifampin. Given the low potency of many second-line antituberculous drugs, we hypothesized that an aggressive regimen of at least 5 likely effective drugs during the intensive phase, including a fluoroquinolone and a parenteral agent, would be associated with a reduced risk of death or treatment failure.Methods. We conducted a retrospective cohort study of patients initiating MDR tuberculosis treatment between 2000 and 2004 in Tomsk, Russian Federation. We used a multivariate Cox proportional hazards model to assess whether monthly exposure to an aggressive regimen was associated with the risk of death or treatment failure.Results. Six hundred fourteen individuals with confirmed MDR tuberculosis were eligible for analysis. On multivariable analysis that adjusted for extensively drug-resistant (XDR) tuberculosis—MDR tuberculosis isolates resistant to fluoroquinolones and parenteral agents—we found that monthly exposure to an aggressive regimen was significantly associated with a lower risk of death or treatment failure (hazard ratio, 0.52 [95% confidence interval, .29–.94]; P = .030).Conclusions. Receipt of an aggressive treatment regimen was a robust predictor of decreased risk of death or failure during MDR tuberculosis treatment. These findings further support the use of this regimen definition as the benchmark for the standard of care of MDR tuberculosis patients and should be used as the basis for evaluating novel therapies. [ABSTRACT FROM AUTHOR]

Where HIV and food insecurity coexist, ready-to-use supplementary foods (RUSFs) are increasingly prescribed to improve patient outcomes. We found no statistically significant differences in outcome with RUSFs vs less expensive corn-soy blend plus rations for HIV patients in rural Haiti.Background. The epidemics of food insecurity, malnutrition, and human immunodeficiency virus (HIV) frequently overlap. HIV treatment programs increasingly provide nutrient-dense ready-to-use supplementary foods (RUSFs) to patients living with HIV and food insecurity, but in the absence of wasting, it is not known if RUSF confers benefit above less costly food commodities.Methods. We performed a randomized trial in rural Haiti comparing an RUSF with less costly corn-soy blend plus (CSB+) as a monthly supplement to patients with HIV infection who were on antiretroviral therapy (ART) <24 months prior to study start. We compared 6- and 12-month outcomes by ration type in terms of immunologic response, body mass index (BMI), adherence to ART, general health quality of life, household food insecurity, and household wealth.Results. A cohort of 524 patients with HIV receiving ART was randomized and followed over time. Median CD4 cell count at baseline was 339 cells/µL (interquartile range [IQR], 197–475 cells/µL) for the CSB+ group, and 341 cells/µL (IQR, 213–464/µL) for the RUSF group. Measured outcomes improved from baseline over time, but there were no statistically significant differences in change for BMI, household wealth index, hunger, general health perception score, or adherence to ART by ration type at 6 or 12 months. The RUSF group had higher CD4 count at 12 months, but this was also not statistically significant.Conclusions. In 12 months of follow-up, there was no statistically significant difference in outcomes between those receiving RUSF-based compared with CSB+-based rations in a cohort of HIV-infected adults on ART in rural Haiti. [ABSTRACT FROM PUBLISHER]

Introduction of the rapid MTBDRplus diagnostic led to a significant improvement in time to multidrug-resistant tuberculosis treatment initiation. However, delays in laboratory processing, result reporting, and therapy initiation require reduction to have maximum impact on treatment outcomes and transmission interruption.Background. Diagnosis of drug resistance and timely initiation of multidrug-resistant (MDR) tuberculosis therapy are essential to reduce transmission and improve patient outcomes. We sought to determine whether implementation of the rapid MTBDRplus diagnostic shortened the time from specimen collection to patient MDR tuberculosis therapy initiation.Methods. We conducted a retrospective cohort analysis of 197 MDR tuberculosis patients treated at Brewelskloof, a rural tuberculosis hospital in Western Cape Province, South Africa, between 2007 and 2011.Results. Eighty-nine patients (45%) were tested using conventional liquid culture and drug susceptibility testing (DST) on solid medium and 108 (55%) were tested using the MTBDRplus assay after positive acid-fast bacilli or culture. Median time from sample taken to therapy initiation was reduced from 80 days (interquartile range [IQR] 62–100) for conventional DST to 55 days (IQR 37.5–78) with the MTBDRplus. Although the laboratory processing time declined significantly, operational delays persisted both in the laboratory and the clinical infrastructure for getting patients started on treatment. In multivariate analysis, patients tested using the MTBDRplus test had a reduced risk of starting treatment 60 days or more after sputum collection of 0.52 (P < .0001) compared with patients tested with culture-based DST, after adjustment for smear status and site of disease.Conclusions. Use of MTBDRplus significantly reduced time to MDR tuberculosis treatment initiation. However, DST reporting to clinics was delayed by more than 1 week due, in part, to laboratory operational delays, including dependence on smear and culture positivity prior to MTBDRplus performance. In addition, once MDR tuberculosis was reported, delays in contacting patients and initiating therapy require improvements in clinical infrastructure. [ABSTRACT FROM AUTHOR]