Tuberculosis treatment loss to follow-up in children exposed at home: A prospective cohort study.

Background: Loss to follow-up (LTFU) from tuberculosis (TB) treatment and care is a significant public health problem. It is important to understand what drives LTFU in children - a population whose treatment and management depend on an adult caregiver - to better provide support services to families affected by TB.

Methods: We conducted a prospective cohort study of household contacts in Lima, Peru (2009-12).

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.

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

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. We aimed to identify characteristics of individuals involved in TB transmission in a community setting, which may guide the prioritization of targeted interventions.

Association between overweight/obesity and multidrug-resistant tuberculosis.

Objective.: To evaluate the association between overweight/obesity and multidrug resistance in patients with and without a history of tuberculosis treatment.

Materials And Methods.

Spatial scale of tuberculosis transmission in Lima, Peru.

Spatially targeted interventions may be effective alternatives to individual or population-based prevention strategies against tuberculosis (TB). However, their efficacy may depend on the mechanisms that lead to geographically constrained hotspots. Local TB incidence may reflect high levels of local transmission; conversely, they may point to frequent travel of community members to high-risk areas.

Higher native Peruvian genetic ancestry proportion is associated with tuberculosis progression risk.

We investigated whether ancestry-specific genetic factors affect tuberculosis (TB) progression risk in a cohort of admixed Peruvians. We genotyped 2,105 patients with TB and 1,320 household contacts (HHCs) who were infected with () but did not develop TB and inferred each individual's proportion of native Peruvian genetic ancestry. Our HHC study design and our data on potential confounders allowed us to demonstrate increased risk independent of socioeconomic factors.

The Contribution of Chest Radiography to the Clinical Management of Children Exposed to Tuberculosis.

Although World Health Organization guidelines emphasize contact investigation for tuberculosis (TB)-exposed children, data that support chest radiography as a useful tool are lacking. We evaluated the diagnostic and prognostic information of chest radiography in children exposed to TB and measured the efficacy of isoniazid preventive therapy (IPT) in those with relevant radiographic abnormalities. Between September 2009 and August 2012, we enrolled 4,468 TB-exposed children who were screened by tuberculin skin testing, symptom assessment, and chest radiography.

Prediction Tool to Identify Children at Highest Risk of Tuberculosis Disease Progression Among Those Exposed at Home.

Background: There is a dearth of research to understand which children, among those who are exposed at home to tuberculosis (TB), are at the highest risk of TB disease, to tailor care. We sought to identify predictors of TB progression in children.

Methods: We conducted a prospective cohort study of children living with adults with pulmonary TB in Lima, Peru (2009-2012).

Smoking Cessation in Tuberculosis Patients and the Risk of Tuberculosis Infection in Child Household Contacts.

Background: While previous studies have shown that cigarette smoking increases the infectiousness of tuberculosis patients, the impact of smoking cessation on tuberculosis transmissibility has not been evaluated.

Methods: Between 2009 and 2012, we enrolled 4500 tuberculosis patients and followed 14 044 household contacts in Lima, Peru. Tuberculosis patients were classified into 4 categories: never smoked, quit in the distant past (stopped smoking >2 months prior to time of diagnosis), recently quit (stopped smoking ≤2 months prior to time of diagnosis), and active smokers.

Tuberculosis clinical presentation and treatment outcomes in pregnancy: a prospective cohort study.

Background: There is limited research to guide TB treatment specifically in pregnant women and few studies have described the presentation of TB in pregnant women. We aimed to understand TB presentation and treatment outcomes in pregnant women in a low HIV burden setting. We describe a cohort of women of childbearing age treated for TB disease in Lima, Peru, and compare clinical presentation and treatment outcomes among pregnant and non-pregnant women between 2009 and 2012, including 36 pregnant women.

Isoniazid Preventive Therapy in Contacts of Multidrug-Resistant Tuberculosis.

The World Health Organization recommends the use of isoniazid (INH) alone or in combination with rifapentine to treat latent tuberculosis infections. The recent rise of drug-resistant tuberculosis has complicated the choice of treatment regimen for latent tuberculosis infection. To evaluate the effects of INH preventive therapy on the contacts of patients with multidrug-resistant tuberculosis.

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

On average, Peruvian individuals are among the shortest in the world. 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.

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.

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.

Transmissibility and potential for disease progression of drug resistant : prospective cohort study.

Objective: To measure the association between phenotypic drug resistance and the risk of tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis.

Setting: 106 district health centers in Lima, Peru between September 2009 and September 2012.

Design: Prospective cohort study.

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.

Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians.

Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5-15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response.

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.

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.

Protective effects of household-based TB interventions are robust to neighbourhood-level variation in exposure risk in Lima, Peru: a model-based analysis.

Background: Untargeted active screening and treatment programmes for tuberculosis (TB) have not been shown to be more effective than passive screening and isoniazid preventive therapy (IPT) for reducing TB incidence. In this manuscript, we compare the efficacy of targeting screening and IPT on high-risk household contacts of diagnosed TB cases, with less-targeted active screening approaches in Lima, Peru.

Methods: We conducted a population-based prospective cohort study within households of TB cases in Lima.

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.

Nutritional Status and Tuberculosis Risk in Adult and Pediatric Household Contacts.

Background: Studies show obesity decreases risk of tuberculosis (TB) disease. There is limited evidence on whether high body mass index also protects against TB infection; how very high body mass indices influence TB risk; or whether nutritional status predicts this risk in children. We assessed the impact of body mass index on incident TB infection and disease among adults and children.

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.