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Background: Depressive disorders are frequently under diagnosed in resource‐limited settings because of lack of access to mental health care or the inability of healthcare providers to recognize them. The Patient Health Questionnaire (PHQ)‐2 and the PHQ‐9 have been widely used for screening and diagnosis of depression in primary care settings; however, the validity of their use in rural, Spanish‐speaking populations is unknown. Method We used a cross‐sectional design to assess the psychometric properties of the PHQ‐9 for depression diagnosis and estimated the sensitivity and specificity of the PHQ‐2 for depression screening. Data were collected from 223 adults in a rural community of Chiapas, Mexico, using the PHQ‐2, the PHQ‐9, and the World Health Organization Quality of Life BREF Scale (WHOQOL‐ BREF). Results: Confirmatory factor analysis suggested that the 1‐factor structure fit reasonably well. The internal consistency of the PHQ‐9 was good (Cronbach's alpha > = 0.8) overall and for subgroups defined by gender, literacy, and age. The PHQ‐9 demonstrated good predictive validity: Participants with a PHQ‐9 diagnosis of depression had lower quality of life scores on the overall WHOQOL‐BREF Scale and each of its domains. Using the PHQ‐9 results as a gold standard, the optimal PHQ‐2 cutoff score for screening of depression was 3 (sensitivity 80.00%, specificity 86.88%, area under receiver operating characteristic curve = 0.89; 95% confidence interval [0.84, 0.94]). Conclusion: The PHQ‐2 and PHQ‐9 demonstrated good psychometric properties, suggesting their potential benefit as tools for depression screening and diagnosis in rural, Spanish‐speaking populations.

Introduction: Integrating mental healthcare into primary care can reduce the global burden of mental disorders. Yet data on the effective implementation of real-world task-shared mental health programmes are limited. In 2012, the Rwandan Ministry of Health and the international healthcare organisation Partners in Health collaboratively adapted the Mentoring and Enhanced Supervision at Health Centers (MESH) programme, a successful programme of supported supervision based on task-sharing for HIV/AIDS care, to include care of neuropsychiatric disorders within primary care settings (MESH Mental Health). We propose 1 of the first studies in a rural low-income country to assess the implementation and clinical outcomes of a programme integrating neuropsychiatric care into a public primary care system. Methods and analysis A mixed-methods evaluation will be conducted. First, we will conduct a quantitative outcomes evaluation using a pretest and post-test design at 4 purposively selected MESH MH participating health centres. At least 112 consecutive adults with schizophrenia, bipolar disorder, depression or epilepsy will be enrolled. Primary outcomes are symptoms and functioning measured at baseline, 8 weeks and 6 months using clinician-administered scales: the General Health Questionnaire and the brief WHO Disability Assessment Scale. We hypothesise that service users will experience at least a 25% improvement in symptoms and functioning from baseline after MESH MH programme participation. To understand any outcome improvements under the intervention, we will evaluate programme processes using (1) quantitative analyses of routine service utilisation data and supervision checklist data and (2) qualitative semistructured interviews with primary care nurses, service users and family members. Ethics and dissemination This evaluation was approved by the Rwanda National Ethics Committee (Protocol #736/RNEC/2016) and deemed exempt by the Harvard University Institutional Review Board. Results will be submitted for peer-reviewed journal publication, presented at conferences and disseminated to communities served by the programme.

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.

Introduction: Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods: A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results: Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions: Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes.

Background: The bivalent whole-cell (BivWC) oral cholera vaccine (Shanchol) is effective in preventing cholera. However, evaluations of immune responses following vaccination with BivWC have been limited. To determine whether BivWC induces significant mucosal immune responses, we measured V. cholerae O1 antigen-specific antibody secreting cell (ASC) responses following vaccination. Methodology/Principal Findings We enrolled 24 Haitian adults in this study, and administered doses of oral BivWC vaccine 14 days apart (day 0 and day 14). We drew blood at baseline, and 7 days following each vaccine dose (day 7 and 21). Peripheral blood mononuclear cells (PBMCs) were isolated, and ASCs were enumerated using an ELISPOT assay. Significant increases in Ogawa (6.9 cells per million PBMCs) and Inaba (9.5 cells per million PBMCs) OSP-specific IgA ASCs were detected 7 days following the first dose (P < 0.001), but not the second dose. The magnitude of V. cholerae-specific ASC responses did not appear to be associated with recent exposure to cholera. ASC responses measured against the whole lipolysaccharide (LPS) antigen and the OSP moiety of LPS were equivalent, suggesting that all or nearly all of the LPS response targets the OSP moiety. Conclusions/Significance: Immunization with the BivWC oral cholera vaccine induced ASC responses among a cohort of healthy adults in Haiti after a single dose. The second dose of vaccine resulted in minimal ASC responses over baseline, suggesting that the current dosing schedule may not be optimal for boosting mucosal immune responses to V. cholerae antigens for adults in a cholera-endemic area.

Vibrio cholerae, the cause of cholera, induces both innate and adaptive immune responses in infected humans. Leptin is a hormone that plays a role in both metabolism and mediating immune responses. We characterized leptin levels in 11 children with cholera in Bangladesh, assessing leptin levels on days 2, 7, 30, and 180 following cholera. We found that patients at the acute stage of cholera had significantly lower plasma leptin levels than matched controls, and compared with levels in late convalescence. We then assessed immune responses to V. cholerae antigens in 74 children with cholera, correlating these responses to plasma leptin levels on day 2 of illness. In multivariate analysis, we found an association between day 2 leptin levels and development of later anti-cholera toxin B subunit (CtxB) responses. This finding appeared to be limited to children with better nutritional status. Interestingly, we found no association between leptin levels and antibody responses to V. cholerae lipopolysaccharide, a T cell–independent antigen. Our results suggest that leptin levels may be associated with cholera, including the development of immune responses to T cell–dependent antigens.

Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs.

Background: To eliminate new pediatric HIV infections, interventions that facilitate adherence, including those that minimize stigma, enhance social support, and mitigate the influence of poverty, will likely be required in addition to combination antiretroviral therapy (ART). We examined the relationship between partner testing and infant outcome in a prevention of parent-to-child transmission of HIV program, which included a family-centered case management approach and a supportive environment for partner disclosure and testing. Design: We analyzed routinely collected data for women and infants who enrolled in the parent-to-child transmission of HIV program at Goroka Family Clinic, Eastern Highlands Provincial Hospital, Papua New Guinea, from 2007 through 2011. Results: Two hundred and sixty five women were included for analysis. Of these, 226 (85%) had a partner, 127 (56%) of whom had a documented HIV test. Of the 102 HIV-infected partners, 81 (79%) had been linked to care. In adjusted analyses, we found a significantly higher risk of infant death, infant HIV infection, or loss to follow-up among mother–infant pairs in which the mother reported having no partner or a partner who was not tested or had an unknown testing status. In a second multivariable analysis, infants born to women with more time on ART or who enrolled in the program in later years experienced greater HIV-free survival. Conclusions: In a program with a patient-oriented and family-centered approach to prevent vertical HIV transmission, the majority of women's partners had a documented HIV test and, if positive, linkage to care. Having a tested partner was associated with program retention and HIV-free survival for infants. Programs aiming to facilitate diagnosis disclosure, partner testing, and linkage to care may contribute importantly to the elimination of pediatric HIV.

Background: Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae. Methodology/Principal Findings We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6–17 years), and 47 younger children (1–5 years) in Haiti, where cholera was introduced in 2010. A≥4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A≥2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age- and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine. Conclusions/Significance: A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae.

Background: Default from multidrug-resistant tuberculosis (MDR-TB) treatment remains a major barrier to cure and epidemic control. We sought to identify patient risk factors for default from MDR-TB treatment and high-risk time periods for default in relation to hospitalization and transition to outpatient care. Methods: We retrospectively analyzed a cohort of 225 patients who initiated MDR-TB treatment between 2007 through 2010 at a rural TB hospital in the Western Cape Province, South Africa. Results: Fifty percent of patients were cured or completed treatment, 27% defaulted, 14% died, 4% failed treatment, and 5% transferred out. Recent alcohol use was common (63% of patients). In multivariable proportional hazards regression, older age (hazard ratio [HR]= 0.97 [95% confidence interval 0.94-0.99] per year of greater age), formal housing (HR=0.38 [0.19-0.78]), and steady employment (HR=0.41 [0.19-0.90]) were associated with decreased risk of default, while recent alcohol use (HR=2.1 [1.1-4.0]), recent drug use (HR=2.0 [1.0-3.6]), and Coloured (mixed ancestry) ethnicity (HR=2.3 [1.1-5.0]) were associated with increased risk of default (P<0.05). Defaults occurred throughout the first 18 months of the two-year treatment course but were especially frequent among alcohol users after discharge from the initial four-to-five-month in-hospital phase of treatment, with the highest default rates occurring among alcohol users within two months of discharge. Default rates during the first two months after discharge were also elevated for patients who received care from mobile clinics. Conclusions: Among patients who were not cured or did not complete MDR-TB treatment, the majority defaulted from treatment. Younger, economically-unstable patients and alcohol and drug users were particularly at risk. For alcohol users as well as mobile-clinic patients, the early outpatient treatment phase is a high-risk period for default that could be targeted in efforts to increase treatment completion rates.