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Experts recommend exclusive breastfeeding from birth to six months because it protects against deadly childhood illness, including respiratory tract infections and diarrhea. We hypothesized that exclusive breastfeeding would decrease the risk of active tuberculosis (TB) in children. We analyzed cross-sectional data from 279 children in Lima, Peru aged 6 to 59 months with TB symptoms and a close adult contact with TB. Mothers self-reported breastfeeding, and children were evaluated for TB per national guidelines. To quantify the association between exclusive breastfeeding and TB, we estimated prevalence ratios using a generalized linear model with a log link, binomial distribution, and robust variance. Twenty-two percent of children were diagnosed with TB and 72% were exclusively breastfed for six months. We found no evidence that six months of exclusive breastfeeding was associated with TB disease in either bivariate analyses (prevalence ratio [PR] = 1.5; 95%CI = 0.8–2.5) or multivariable analyses adjusting for sex and socioeconomic status (adjusted PR = 1.6; 95%[CI] = 0.9–2.7). In post hoc analyses among children whose close TB contact was their mother, we found evidence of a weak positive association between breastfeeding and TB (aPR = 2.1; 95%[CI] = 0.9–4.9). This association was not apparent among children whose close contact was not the mother (aPR = 1.2; 95%[CI] = 0.6–2.4). Our results raise the possibility that children who are breastfed by mothers with TB may be at increased risk for TB, given the close contact. Due to the cross-sectional study design, these results should be interpreted with caution. If these findings are confirmed in longitudinal analyses, future interventions could aim to minimize TB transmission from mothers with TB to breastfeeding infants. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) diagnosis relies on a sputum sample, which cannot be easily obtained from all symptomatic patients. Mycobacterium tuberculosis DNA can be detected from oral swabs, a noninvasive, safe alternative sample type; however, reported sensitivities have been variable and likely depend on sample collection, processing procedures and host characteristics. We analyzed three buccal swab samples from 123 adults with culture-confirmed TB in Lima, Peru. We compared the sensitivity and specificity of two sample collection devices (OmniSwab and EasiCollect FTA cards) and examined factors associated with detection. DNA was extracted with a commercially available kit and detected via real-time PCR IS6110 amplification. Overall sensitivity for buccal samples was 51% (95% Confidence Interval [CI] 42–60%). Specificity from a single sample among healthy controls was 96.7% (95% CI 83–99.9%). Positive sputum smear and cavitary disease, correlates of disease burden, were associated with detection via buccal swab. Although we observed higher sensitivities with the Omniswab samples, this appeared to be due primarily to differences in patient characteristics (e.g., cavitary disease). Overall, our findings support the potential for a buccal sample-based TB assay. Future work should focus on assay optimization and streamlining the assay workflow. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The enteric string test can be used to obtain a specimen for microbiological confirmation of tuberculosis in children, but it is not widely used for this. The aim of this analysis to evaluate this approach in children with tuberculosis symptoms.Methods: We conducted a cross-sectional study to assess children's ability to complete the test (feasibility), and self-reported pain (tolerability). We examined caregivers' and children's willingness to repeat the procedure (acceptability) and described the diagnostic yield of cultures for diagnostic tools. We stratified estimates by age and compared metrics to those derived for gastric aspirate (GA).Results: Among 148 children who attempted the string test, 34% successfully swallowed the capsule. Feasibility was higher among children aged 11-14 than in children 4-10 years (83% vs 22% respectively, p < 0.0001). The string test was better tolerated than GA in both age groups; however, guardians and older children reported higher rates of willingness to repeat GA than the string test (86% vs. 58% in children; 100% vs. 83% in guardians). In 9 children with a positive sputum culture, 6 had a positive string culture. The one children with a positive gastric aspirate culture also had a positive string culture.Conclusion: Although the string test was generally tolerable and accepted by children and caregivers; feasibility in young children was low. Reducing the capsule size may improve test success rates in younger children. [ABSTRACT FROM AUTHOR]

Two cases of multidrug-resistant tuberculosis (MDR TB) in a household are assumed to reflect within-household transmission. However, in high-incidence areas of MDR TB, secondary cases may arise through exposure to MDR TB in the community. To estimate the frequency of multiple introductions of MDR TB into households, we used spoligotyping and 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeats to classify isolates from 101 households in Lima, Peru, in which >1 MDR TB patient received treatment during 1996-2004. We found different MDR TB strains in ≥10% of households. Alternate approaches for classifying matching strains produced estimates of multiple introductions in ≤38% of households. At least 4% of MDR TB patients were reinfected by a second strain of MDR Mycobacterium tuberculosis. These findings suggest that community exposure to MDR TB in Lima occurs frequently. Rapid drug sensitivity testing of strains from household contacts of known MDR TB patients is needed to identify optimal treatment regimens. [ABSTRACT FROM AUTHOR]

Following publication of the original article [1]. The authors reported that there is a mistake in Fig. 1: the number of patients in the control group its 449 patients, instead of 455. [ABSTRACT FROM AUTHOR]

Background: Rapid and accurate diagnosis of childhood tuberculosis (TB) is challenging because children are often unable to produce the sputum sample required for conventional tests. Stool is an alternative sample type that is easy to collect from children, and studies investigating the use of stool for molecular detection of Mycobacterium tuberculosis (Mtb) have led to promising results. Our objective was to evaluate stool as an alternative specimen to sputum for Mtb detection in children. We did so using the TruTip workstation (Akonni Biosystems), a novel automated lysis and extraction platform.Methods: We tested stool samples from 259 children aged 0-14 years old, in Lima, Peru who presented with TB symptoms. Following extraction with TruTip, we detected the presence of Mtb DNA by IS6110 real-time PCR. We calculated assay sensitivity in two groups: (1) children with culture confirmed TB (N = 22); and (2) children with clinically-diagnosed unconfirmed TB (N = 84). We calculated specificity among children in whom TB was ruled out (N = 153). Among children who were diagnosed with TB, we examined factors associated with a positive stool test.Results: Assay sensitivity was 59% (95% confidence interval [CI]: 39-80%) and 1.2% (95% CI: 0.0-6.5%) in children with culture-confirmed and clinically-diagnosed unconfirmed TB, respectively, and specificity was 97% (95% CI: 93-99%). The assay detected Mtb in stool of 7/7 children with smear-positive TB (100% sensitivity; 95% CI: 59-100%), and in 6/15 of children with smear-negative, culture-confirmed TB (40% sensitivity; 95% CI: 16-68%). Older age, smear positivity, culture positivity, ability to produce sputum and cavitary disease were associated with a positive stool result.Conclusion: Testing of stool samples with the TruTip workstation and IS6110 amplification yielded sensitivity and specificity estimates comparable to other tests such as Xpert. Future work should include detection of resistance using the TruTip closed amplification system and assay optimization to improve sensitivity in children with low bacillary loads. [ABSTRACT FROM AUTHOR]

Objective: Diagnostic testing for tuberculosis depends on microbiological detection of Mycobacterium tuberculosis (Mtb) in sputum. For patients unable to expectorate sputum, such as children and individuals living with HIV, this poses barriers to rapid diagnosis and treatment initiation. Therefore, this study aimed to use oral swabs as an alternative sample type for Mtb detection via molecular testing. Results: In a pilot study, we aimed to evaluate sensitivity of Mtb detection via oral swabs using Xpert MTB/RIF ULTRA. We enrolled 33 TB cases and 30 controls from Lima, Peru, and detected Mtb from oral swabs with a sensitivity of 45% (95% confidence interval (CI) 29–62%) and specificity of 100% (95% CI 89–100%) using liquid culture of sputum as reference test. Our current protocol will need optimization, but these results support future exploration of the use of oral swabs for Mtb detection. [ABSTRACT FROM AUTHOR]