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Recognizing the key role early detection plays in interrupting further tuberculosis (TB) transmission, the World Health Organization (WHO) has emphasized the need for global investment in that area. In line [...]

Tuberculosis (TB) is the leading infectious cause of death globally and the 9th leading cause overall (1). TB causes [approximately equals to] 10 million new cases and 1.7 million deaths [...]

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. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains the leading cause of death worldwide from a single infectious disease; in 2017, [approximately equal to]10 million incident cases and 1.7 million deaths were reported (1). The [...]

Within-host heterogeneity of Mycobacterium tuberculosis infection is increasingly recognized as an obstacle for the accurate diagnosis (1) and effective treatment (2) of tuberculosis (TB) and may complicate the control of [...]

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 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., Author(s): Omowunmi Aibana 1, Chuan-Chin Huang 2, Said Aboud 3, Alberto Arnedo-Pena 4, Mercedes C. Becerra 2, Juan Bautista Bellido-Blasco 4, Ramesh Bhosale 5, Roger Calderon 6, Silvia Chiang 7, [...]

Spatially targeted interventions may be effective alternatives to individual or populationbased 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. We used whole-genome sequencing to explore patterns of TB incidence and transmission in Lima, Peru. Between 2009 and 2012, we recruited incident pulmonary TB patients and their household contacts, whom we followed for the occurrence of TB disease. We used whole-genome sequences of 2,712 Mycobacterial tuberculosis isolates from 2,440 patients to estimate pariwise genomic distances and compared these to the spatial distance between patients’ residences. Genomic distances increased rapidly as spatial distances increased and remained high beyond 2 km of separation. Next, we divided the study catchment area into 1 × 1 km grid-cell surface units and used household spatial coordinates to locate each TB patient to a specific cell. We estimated cell-specific transmission by calculating the proportion of patients in each cell with a pairwise genomic distance of 10 or fewer single-nucleotide polymorphisms. We found that cell-specific TB incidence and local transmission varied widely but that cell-specific TB incidence did not correlate closely with our estimates of local transmission (Cohen’s k = 0.27). These findings indicate that an understanding of the spatial heterogeneity in the relative proportion of TB due to local transmission may help guide the implementation of spatially targeted interventions. [ABSTRACT FROM AUTHOR]

The discovery and use of discriminating genetic markers such as IS6110 restriction fragment length polymorphisms (RFLPs), spacer oligonucleotides (spoligotyping), and mycobacterial interspersed repetitive unit--variable number tandem repeats (MIRU-VNTRs) (1) have [...]

A recent analysis of global tuberculosis (TB) case notification data estimated that only 27% of new smear positive cases that arose in 2000 were detected by the current recommended strategy […]

Abstract Background In 2006, we were funded by the US National Institutes of Health to implement a study of tuberculosis epidemiology in Peru. The study required a secure information system to manage data from a target goal of 16,000 subjects who needed to be followed for at least one year. With previous experience in the development and deployment of web-based medical record systems for TB treatment in Peru, we chose to use the OpenMRS open source electronic medical record system platform to develop the study information system. Supported by a core technical and management team and a large and growing worldwide community, OpenMRS is now being used in more than 40 developing countries. We adapted the OpenMRS platform to better support foreign languages. We added a new module to support double data entry, linkage to an existing laboratory information system, automatic upload of GPS data from handheld devices, and better security and auditing of data changes. We added new reports for study managers, and developed data extraction tools for research staff and statisticians. Further adaptation to handle direct entry of laboratory data occurred after the study was launched. Results Data collection in the OpenMRS system began in September 2009. By August 2011 a total of 9,256 participants had been enrolled, 102,274 forms and 13,829 laboratory results had been entered, and there were 208 users. The system is now entirely supported by the Peruvian study staff and programmers. Conclusions The information system served the study objectives well despite requiring some significant adaptations mid-stream. OpenMRS has more tools and capabilities than it did in 2008, and requires less adaptations for future projects. OpenMRS can be an effective research data system in resource poor environments, especially for organizations using or considering it for clinical care as well as research.

Background International guidelines recommend monitoring weight as an indicator of therapeutic response in childhood tuberculosis (TB) disease. This recommendation is based on observations in adults. In the current study, we evaluated the association between weight change and treatment outcome, the accuracy of using weight change to predict regimen efficacy, and whether successfully treated children achieve catch-up weight gain. Methods We enrolled children treated for drug-susceptible TB disease (group 1) and multidrug-resistant TB disease (group 2) in Peru. We calculated the change in weight-for-age z score (ΔWAZ) between baseline and the end of treatment months 2–5 for group 1, and between baseline and months 2–8 for group 2. We used logistic regression and generalized estimating equation models to evaluate the relationship between ΔWAZ and outcome. We plotted receiver operating characteristic curves to determine the accuracy of ΔWAZ for predicting treatment failure or death. Results Groups 1 and 2 included 100 and 94 children, respectively. In logistic regression, lower ΔWAZ in months 3–5 and month 7 was associated with treatment failure or death in groups 1 and 2, respectively. In generalized estimating equation models, children in both groups who experienced treatment failure or death had lower ΔWAZ than successfully treated children. The ΔWAZ predicted treatment failure or death with 60%–90% sensitivity and 60%–86% specificity in months 2–5 for group 1 and months 7–8 for group 2. All successfully treated children—except group 2 participants with unknown microbiologic confirmation status—achieved catch-up weight gain. Conclusions Weight change early in therapy can predict the outcome of childhood TB treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]