A positively selected FBN1 missense variant reduces height in Peruvian individuals.

On average, Peruvian individuals are among the shortest in the world1. Here we show that Native American ancestry is associated with reduced height in an ethnically diverse group of Peruvian individuals, and identify a population-specific, missense variant in the FBN1 gene (E1297G) that is significantly associated with lower height. Each copy of the minor allele (frequency of 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). To our knowledge, this is the largest effect size known for a common height-associated variant. FBN1 encodes the extracellular matrix protein fibrillin 1, which is a major structural component of microfibrils. We observed less densely packed fibrillin-1-rich microfibrils with irregular edges in the skin of individuals who were homozygous for G1297 compared with individuals who were homozygous for E1297. Moreover, we show that the E1297G locus is under positive selection in non-African populations, and that the E1297 variant shows subtle evidence of positive selection specifically within the Peruvian population. This variant is also significantly more frequent in coastal Peruvian populations than in populations from the Andes or the Amazon, which suggests that short stature might be the result of adaptation to factors that are associated with the coastal environment in Peru.

Who Transmits Tuberculosis to Whom: A Cross-Sectional Analysis of a Cohort Study in Lima, Peru.

Rationale: The persistent burden of tuberculosis (TB) disease emphasizes the need to identify individuals with TB for treatment and those at a high risk of incident TB for prevention. Targeting interventions toward those at high risk of developing and transmitting TB is a public health priority. Objectives: We aimed to identify characteristics of individuals involved in TB transmission in a community setting, which may guide the prioritization of targeted interventions. Methods: We collected clinical and sociodemographic data from a cohort of patients with TB in Lima, Peru. We used whole-genome sequencing data to assess the genetic distance between all possible pairs of patients; we considered pairs to be the result of a direct transmission event if they differed by three or fewer SNPs, and we assumed that the first diagnosed patient in a pair was the transmitter and the second was the recipient. We used logistic regression to examine the association between host factors and the likelihood of direct TB transmission. Measurements and Main Results: Analyzing data from 2,518 index patients with TB, we identified 1,447 direct transmission pairs. Regardless of recipient attributes, individuals less than 34 years old, males, and those with a history of incarceration had a higher likelihood of being transmitters in direct transmission pairs. Direct transmission was more likely when both patients were drinkers or smokers. Conclusions: This study identifies men, young adults, former prisoners, alcohol consumers, and smokers as priority groups for targeted interventions. Innovative strategies are needed to extend TB screening to social groups such as young adults and prisoners with limited access to routine preventive care.

Chest Radiograph Screening for Detecting Subclinical Tuberculosis in Asymptomatic Household Contacts, Peru.

The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.

Prevalence of non-communicable diseases among household contacts of people with tuberculosis: A systematic review and individual participant data meta-analysis.

OBJECTIVE: To investigate the prevalence of non-communicable diseases among household contacts of people with tuberculosis. METHODS: We conducted a systematic review and individual participant data meta-analysis. We searched Medline, Embase and the Global Index Medicus from inception to 16 May 2023. We included studies that assessed for at least one non-communicable disease among household contacts of people with clinical tuberculosis. We estimated the non-communicable disease prevalence through mixed effects logistic regression for studies providing individual participant data, and compared it with estimates from aggregated data meta-analyses. Furthermore, we compared age and sex-standardised non-communicable disease prevalence with national-level estimates standardised for age and sex. RESULTS: We identified 39 eligible studies, of which 14 provided individual participant data (29,194 contacts). Of the remaining 25 studies, 18 studies reported aggregated data suitable for aggregated data meta-analysis. In individual participant data analysis, the pooled prevalence of diabetes in studies that undertook biochemical testing was 8.8% (95% confidence interval [CI], 5.1%-14.9%, four studies). Age-and sex-standardised prevalence was higher in two studies (10.4% vs. 6.9% and 11.5% vs. 8.4%) than the corresponding national estimates and similar in two studies. Prevalence of diabetes mellitus based on self-report or medical records was 3.4% (95% CI 2.6%-4.6%, 14 studies). Prevalence did not significantly differ compared to estimates from aggregated data meta-analysis. There were limited data for other non-communicable diseases. CONCLUSION: The prevalence of diabetes mellitus among household contacts was high while that of known diabetes was substantially lower, suggesting the underdiagnosis. tuberculosis household contact investigation offers opportunities to deliver multifaceted interventions to identify tuberculosis infection and disease, screen for non-communicable diseases and address shared risk factors.

Brief virtual intervention associated with increased social engagement and decreased negative affect among people aging with HIV.

Virtual Villages-online communities that deliver supports to promote aging in place-are proposed to mitigate isolation and support the health of aging populations. Using a community-engaged approach, we developed and pilot-tested a Virtual Village intervention tailored for people living with HIV (PLWH) aged 50+ . The intervention employed a Discord server featuring social interaction, regional and national resources, expert presentations, and mindful meditation exercises. In 2022, a sample of PLWH aged 50+ from three U.S. study sites participated in a four-week pilot. Pre- and post-intervention surveys assessed participants' demographic characteristics; degree of loneliness, social connectedness, HIV-related stigma, and technology acceptance; mental wellbeing and physical health outcomes; and user experience. Participants (N = 20) were socioeconomically and racially/ethnically diverse, aged 51-88 years, and predominantly identified as gay or bisexual men (75%). Paired t-tests revealed a significant increase in participants' mean social engagement scores and a significant decrease in participants' mean negative affect scores, following the intervention. User experience scores were acceptable and participants reported a positive sense of connectedness to the Virtual Village community. Results suggest that a virtual community can be accessible to older PLWH and may enhance social engagement and improve aspects of mental wellbeing.

A community-academic partnered approach to designing a Virtual Village to address the needs of older adults living with HIV.

ABSTRACTMany older adults living with HIV face unique challenges, including comorbidities, loneliness, and isolation. This community-academic partnered study elicited viewpoints from older adults living with HIV about the characteristics of a digital environment ("Virtual Village") to combat against loneliness and isolation. We utilized Choice-Based Conjoint Analyses to determine preferred attributes of a Virtual Village. We also conducted focus groups and interviews with older adults living with HIV and used an iterative, data-driven approach to systematically identify emergent themes. Participants (N = 82) were aged 50-82 years and racially/ethnically diverse. The majority were men (78%), gay (66%), and lived with HIV for ≥15 years (83%). Cost was the factor that most drove participants' preference for joining a Virtual Village. Thematic concerns included lack of technological confidence, internet access, potential for harassment in digital environments, privacy, and preference for in-person interactions. Praises centered on convenience and making connections across geographic distances. Participants emphasized the need for purposive strategies to form a cohesive and supportive community for older adults living with HIV. A moderated environment was recommneded to create a safe, structured, and comfortable digital environment for older adults living with HIV. A Virtual Village should be viewed as a bridge to in-person interactions.

MSW Students' Perspectives on Learning and Delivering a Protocolized, Low-Intensity Transdiagnostic Psychological Intervention: Implications for Experiential Learning.

Problem Management Plus (PM+) is a protocolized, low-intensity, transdiagnostic psychological intervention designed to be delivered by lay individuals. Faculty at the University of South Florida School of Social Work recognized PM + as a potential psychological intervention for master's students to learn to complement their clinical coursework and simultaneously provide an experiential learning experience to support their clinical skills. Before this pilot, the feasibility and acceptability of integrating PM + into a Master of Social Work (MSW) setting were unknown. Upon analyzing the students' feedback using inductive content analysis, it is evident that experiential learning using interventions is crucial to building the self-efficacy of MSW students. Students reported that PM + helped their personal mental health and client interactions, using the tools they learned even a year after the pilot. Future research should focus on integrating PM + into experiential learning experiences within social work and allied academic settings and professions.

Attitudes Toward Payment for Research Participation: Results from a U.S. Survey of People Living with HIV.

Little is known about how payment affects individuals' decisions to participate in HIV research. Using data from a U.S. survey of people living with HIV (N = 292), we examined potential research participants' attitudes toward payment, perceived study risk based on payment amount, and preferred payment forms, and how these factors vary by sociodemographic characteristics. Most respondents agreed people should be paid for HIV research participation (96%) and said payment would shape their research participation decisions (80%). Men, less formally educated individuals, and members of some minoritized racial-ethnic groups were less likely to be willing to participate in research without payment. Higher payment was associated with higher perceived study risks, while preferences for form of payment varied by age, gender, education, race-ethnicity, and census region of residence. Findings suggest payment may influence prospective research participants' risk-benefit calculus and participation, and that a one-size-fits-all approach to payment could differentially influence participation among distinct sociodemographic groups.

RESUMEN: Se sabe poco acerca de cómo el pago afecta a la decisión de participar en investigaciones sobre VIH. Utilizando data de una encuesta de Estados Unidos sobre personas viviendo con VIH (N = 292), se examinó la actitud de potenciales participantes de investigación acerca del pago, el riesgo de estudio percibido basado en la cantidad del pago, las formas de pago preferidas y cómo estos factores varían según las características sociodemográficas. La mayoría de los que respondieron la encuesta estuvieron de acuerdo en que las personas debían recibir un pago por participar en una investigación sobre VIH (96%) y dijeron que el pago podría moldear su decisión de participar en la investigación (80%). Los hombres, individuos con menor educación formal y los miembros de algún grupo racial-étnico minoritario se mostraron menos propensos a participar en una investigación sin recibir pago. Se asoció un pago más alto con una mayor percepción de riesgos en el estudio, mientras que las preferencias por las formas de pago variaron según la edad, el género, la educación, la raza-etnicidad y la región. Los resultados sugirieron que el pago podría influir en el cálculo del riesgo-beneficio y en la participación de los potenciales participantes en una investigación prospectiva, y que un enfoque único para el pago podría influir de manera diferencial entre los distintos grupos sociodemográficos en lo que respecta a su participación.

High levels of mild to moderate depression among men who have sex with men and transgender women in Lima, Peru: implications for integrated depression and HIV care.

ABSTRACTDepression disproportionally affects people at risk of acquiring or living with HIV and is associated with worse health outcomes; however, depression care is not routinely integrated with HIV prevention and treatment services. Selection of the best depression intervention(s) for integration depends both on the prevalence and severity of depression among potential users. To inform depression care integration in a community-based setting in Lima, Peru, we retrospectively analyzed routinely collected depression screening data from men who have sex with men and transgender women seeking HIV prevention and care services (N = 185). Depression was screened for using the Patient Health Questionnaire-9. Prevalence of any depression (PHQ-9 ≥ 5) was 42% and was significantly associated with the last sexual partner being "casual" (p = 0.01). Most (81%) depressive symptoms were mild to moderate (≥5 PHQ-9 ≤ 14). Integrating depression care with HIV prevention and treatment services in Peru should begin by implementing interventions targeting mild to moderate depression.

Toward patient-centered tuberculosis preventive treatment: preferences for regimens and formulations in Lima, Peru.

BACKGROUND: To ensure patient-centered tuberculosis preventive treatment, it is important to consider factors that make it easier for patients to complete treatment. However, there is little published literature about patient preferences for different preventive treatment regimen options, particularly from countries with high tuberculosis burdens. METHODS: We conducted a qualitative research study using a framework analysis approach to understand tuberculosis preventive treatment preferences among household contacts. We conducted three focus group discussions with 16 members of families affected by tuberculosis in Lima, Peru. Participants were asked to vote for preferred preventive treatment regimens and discuss the reasons behind their choices. Coding followed a deductive approach based on prior research, with data-driven codes added. RESULTS: In total, 7 (44%) participants voted for 3 months isoniazid and rifapentine, 4 (25%) chose 3 months isoniazid and rifampicin, 3 (19%) chose 4 months rifampicin, and 2 (13%) chose 6 months isoniazid. Preferences for shorter regimens over 6 months of isoniazid were driven by concerns over "getting tired" or "getting bored" of taking medications, the difficulty of remembering to take medications, side effects, and interference with daily life. For some, weekly dosing was perceived as being easier to remember and less disruptive, leading to a preference for 3 months isoniazid and rifapentine, which is dosed weekly. However, among caregivers, having a child-friendly formulation was more important than regimen duration. Caregivers reported difficulty in administering pills to children, and preferred treatments available as syrup or dispersible formulations. CONCLUSIONS: There is demand for shorter regimens and child-friendly formulations for tuberculosis preventive treatment in high-burden settings. Individual preferences differ, suggesting that patient-centered care would best be supported by having multiple shorter regimens available.

Access of Mental Health Services by the Adult Population in Metropolitan Lima, Peru: Characteristics, Perceptions and Need for Care.

This study aimed to characterize mental health service access in metropolitan Lima, Peru. Between May and December 2012, we interviewed 4,445 Peruvian adults, applying the Mini-International Neuropsychiatric Interview (MINI); a modified version of the WHO Disability Assessment Schedule (WHODAS-S); and, a health services access questionnaire. In the prior year, 3.6% (95% CI 3.0-4.4) of respondents accessed mental health services. Care access was associated with female sex; being unemployed; and having a diagnosed psychiatric morbidity. Of those with psychiatric morbidity, 16.9% (95% CI 13.3-21.3) received clinical care. Care access was 25.8% (95% CI 19.9-32.8) for people with a depressive episode; 12.1% (95% CI 7.4-19.2) for any anxiety disorder; and, 5.9% (95% CI 1.7-18.6) for harmful alcohol consumption or dependence. Respondents with moderate to severe levels of disability were more likely to recognize the need for care, but this was not necessarily associated with higher care access. Reducing the mental, neurological and substance use disorders treatment gap in Peru are discussed in light of the findings.

Two Clinical Prediction Tools to Improve Tuberculosis Contact Investigation.

BACKGROUND: Efficient contact investigation strategies are needed for the early diagnosis of tuberculosis (TB) disease and treatment of latent TB infections. METHODS: Between September 2009 and August 2012, we conducted a prospective cohort study in Lima, Peru, in which we enrolled and followed 14 044 household contacts of adults with pulmonary TB. We used information from a subset of this cohort to derive 2 clinical prediction tools that identify contacts of TB patients at elevated risk of progressing to active disease by training multivariable models that predict (1) coprevalent TB among all household contacts and (2) 1-year incident TB among adult contacts. We validated the models in a geographically distinct subcohort and compared the relative utilities of clinical decisions based on these tools to existing strategies. RESULTS: In our cohort, 296 (2.1%) household contacts had coprevalent TB and 145 (1.9%) adult contacts developed incident TB within 1 year of index patient diagnosis. We predicted coprevalent disease using information that could be readily obtained at the time an index patient was diagnosed and predicted 1-year incident TB by including additional contact-specific characteristics. The area under the receiver operating characteristic curves for coprevalent TB and incident TB were 0.86 (95% confidence interval [CI], .83-.89]) and 0.72 (95% CI, .67-.77), respectively. These clinical tools give 5%-10% higher relative utilities than existing methods. CONCLUSIONS: We present 2 tools that identify household contacts at high risk for TB disease based on reportable information from patient and contacts alone. The performance of these tools is comparable to biomarkers that are both more costly and less feasible than this approach.

Mycobacterium tuberculosis Beijing Lineage and Risk for Tuberculosis in Child Household Contacts, Peru.

Few studies have prospectively compared the relative transmissibility and propensity to cause disease of Mycobacterium tuberculosis Beijing strains with other human-adapted strains of the M. tuberculosis complex. We assessed the effect of Beijing strains on the risk for M. tuberculosis infection and disease progression in 9,151 household contacts of 2,223 culture-positive pulmonary tuberculosis (TB) patients in Lima, Peru. Child contacts exposed to Beijing strains were more likely than child contacts exposed to non-Beijing strains to be infected at baseline, by 12 months of follow-up, and during follow-up. We noted an increased but nonsignificant tendency for child contacts to develop TB. Beijing strains were not associated with TB in adult contacts. These findings suggest that Beijing strains are more transmissible in children than are non-Beijing strains.

The Use of Wearable Technology to Objectively Measure Sleep Quality and Physical Activity Among Pregnant Women in Urban Lima, Peru: A Pilot Feasibility Study.

INTRODUCTION: Sleep quality and physical activity can affect the mental and physical health of pregnant women and their babies in utero. METHODS: We investigated the feasibility of objectively assessing sleep quality and physical activity among resource-constrained, pregnant women in urban Lima, Peru. Twenty pregnant women were asked to complete written sleep logs and wear ActiSleep, a wristwatch-like device that records sleep quality (consecutive minutes of uninterrupted sleep) and physical activity (steps), for seven consecutive days. Sociodemographic data and pregnancy characteristics were also collected. RESULTS: Of twenty women, 13 (65%) had sufficient data collected for analysis. The mean age of study participants was 26.3 years (SD = 3.9), with a mean sleep duration of 6.9 h (SD = 1.4). The median time for sleep onset was 21:15. The mean time for sleep latency was 17.3 min; and wake after sleep onset was 116 min. The mean number of awakenings was 20.4 (SD = 6.7); and sleep efficiency was 77.9%. For physical activity, participants averaged of 6,029 steps per day (SD = 3,087). DISCUSSION: Objective assessment of sleep quality and physical activity among pregnant women in a resource-constrained setting was promising, despite modest data collection completeness. Wearable technology could be used in health interventions to improve sleep quality and physical activity among this population.

Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Individual-level characteristics associated with oral HIV test acceptability among Peruvian men who have sex with men and transgender women: a cross-sectional study.

OBJECTIVES: Peruvian men who have sex with men (MSM) and transgender women (TGW) are highly vulnerable to HIV infection (HIV), but stigma, access issues and fear of venipuncture hamper testing. The oral HIV test-which uses oral fluids and provides results in 20 minutes-could reduce these barriers. The objective of this study was to determine the acceptability of the oral HIV test and the individual-level factors associated with its acceptability among MSM and TGW. METHODS: We conducted a cross-sectional secondary analysis among Peruvian MSM and TGW attending a community-based health centre between February 2012 and February 2013 to determine the individual-level factors associated with oral HIV test acceptability. RESULTS: Of 334 participants, 88% were MSM and 12% TGW. Overall, 85% of participants indicated their acceptability of the oral HIV test. Acceptability was higher in MSM than TGW (85.7% vs 80.0%) but this difference was not significant. Factors associated with acceptability in MSM were: tertiary or higher education (prevalence ratio (PR)=1.18, 95% CI 1.06 to 1.32 and PR=1.16, 95% CI 1.03 to 1.30, respectively); sex with drug use (PR=1.19, 95% CI 1.05 to 1.36); believing that HIV is transmitted by saliva (PR=1.20, 95% CI 1.08 to 1.33); and potential use of the oral test at home (PR=1.56, 95% CI 1.32 to 1.85). The only factor associated with lower acceptability was having had first anal intercourse between 14 and 19 years of age (PR=0.89, 95% CI 0.80 to 0.98). CONCLUSIONS: We identified the individual factors associated with oral HIV test acceptability among Peruvian MSM and TGW. Expanded use of the oral HIV test to increase testing rates among Peruvian MSM and TGW is recommended. TRIAL REGISTRATION NUMBER: NCT01387412, post-results.

Vitamin E Status Is Inversely Associated with Risk of Incident Tuberculosis Disease among Household Contacts.

Background: Few studies have previously assessed how pre-existing vitamin E status is associated with risk of tuberculosis (TB) disease progression. Objective: We evaluated the association between baseline plasma concentrations of 3 vitamin E isomers (α-tocopherol, γ-tocopherol, and δ-tocopherol) and TB disease risk. Methods: We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary TB cases in Lima, Peru. We defined cases as HHCs who developed active TB disease ≥15 d after the diagnosis of the index patient, and we matched each case to 4 control cases who did not develop active TB based on age by year and gender. We used univariate and multivariate conditional logistic regression to calculate ORs for incident TB disease by plasma concentrations of α-tocopherol, γ-tocopherol, and δ-tocopherol. Results: Among 6751 HIV-negative HHCs who provided baseline blood samples, 180 developed secondary TB during follow-up. After controlling for possible confounders, we found that baseline α-tocopherol deficiency conferred increased risk of incident TB disease (adjusted OR: 1.59; 95% CI: 1.02, 2.50; P = 0.04). Household contacts in the lowest tertile of δ-tocopherol were also at increased risk of progression to TB disease compared to those in the highest tertile (tertile 1 compared with tertile 3, adjusted OR: 2.29; 95% CI: 1.29, 4.09; P-trend = 0.005). We found no association between baseline concentration of γ-tocopherol and incident TB disease. Conclusions: Vitamin E deficiency was associated with an increased risk of progression to TB disease among HHCs of index TB cases. Assessment of vitamin E status among individuals at high risk for TB disease may play a role in TB control efforts.

Impact of Vitamin A and Carotenoids on the Risk of Tuberculosis Progression.

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.

Polyclonal Pulmonary Tuberculosis Infections and Risk for Multidrug Resistance, Lima, Peru.

Because within-host Mycobacterium tuberculosis diversity complicates diagnosis and treatment of tuberculosis (TB), we measured diversity prevalence and associated factors among 3,098 pulmonary TB patients in Lima, Peru. The 161 patients with polyclonal infection were more likely than the 115 with clonal or the 2,822 with simple infections to have multidrug-resistant TB.

Pyrazinamide Resistance Assays and Two-Month Sputum Culture Status in Patients with Multidrug-Resistant Tuberculosis.

Phenotypic drug susceptibility testing is the current "gold standard" for detecting Mycobacterium tuberculosis susceptibility to antituberculous drugs. Pyrazinamide is one antituberculous drug for which the correlation between in vitro resistance and clinical outcomes remains unclear. Here we performed latent class analysis (LCA) to develop a consensus gold standard definition of pyrazinamide resistance using three paired standard pyrazinamide resistance assays. We then compared this consensus measure to the 2-month culture results for patients with multidrug-resistant tuberculosis (MDR-TB) who were treated for 2 months with first-line antituberculous drugs before their resistance results were known. Among 121 patients with MDR-TB, 60 (49.6%) were resistant to pyrazinamide by the Wayne method (L. G. Wayne, Am Rev Respir Dis 109:147-151, 1974), 71 (58.7%) were resistant by the Bactec MGIT 960 method, and 68 (56.2%) were resistant by pncA sequencing. LCA grouped isolates with positive results by at least two assays into a category which we considered the "consensus gold standard" for pyrazinamide resistance. The sensitivity and specificity for this consensus gold standard were 82.4% and 92.5%, respectively, for the Wayne method; 95.6% and 88.7%, respectively, for the Bactec MGIT 960 method; and 92.6% and 90.6%, respectively, for pncA sequencing. After we adjusted for other factors associated with poor outcomes, including age, sex, alcohol use, and baseline ethambutol resistance, patients whose isolates were resistant by the LCA-derived consensus gold standard were more likely to be culture positive at 2 months with an odds ratio of 1.95 (95% confidence interval, 0.74 to 5.11), but this result was not statistically significant. These findings underscore the need for improved diagnostics for routine use in programmatic settings.