Household Contacts Of Tuberculosis Cases Research Articles

MR1-restricted T cell clonotypes are associated with "resistance" to Mycobacterium tuberculosis infection.

T cells are required for protective immunity against Mycobacterium tuberculosis. We recently described a cohort of Ugandan household contacts of tuberculosis cases who appear to "resist" M. tuberculosis infection (resisters; RSTRs) and showed that these individuals harbor IFN-γ-independent T cell responses to M. tuberculosis-specific peptide antigens. However, T cells also recognize nonprotein antigens via antigen-presenting systems that are independent of genetic background, known as donor-unrestricted T cells (DURTs). We used tetramer staining and flow cytometry to characterize the association between DURTs and "resistance" to M. tuberculosis infection. Peripheral blood frequencies of most DURT subsets were comparable between RSTRs and latently infected controls (LTBIs). However, we observed a 1.65-fold increase in frequency of MR1-restricted T (MR1T) cells among RSTRs in comparison with LTBIs. Single-cell RNA sequencing of 18,251 MR1T cells sorted from 8 donors revealed 5,150 clonotypes that expressed a common transcriptional program, the majority of which were private. Sequencing of the T cell receptor α/T cell receptor δ (TCRα/δ) repertoire revealed several DURT clonotypes were expanded among RSTRs, including 2 MR1T clonotypes that recognized mycobacteria-infected cells in a TCR-dependent manner. Overall, our data reveal unexpected donor-specific diversity in the TCR repertoire of human MR1T cells as well as associations between mycobacteria-reactive MR1T clonotypes and resistance to M. tuberculosis infection.

Using the Health Belief Model to Predict Tuberculosis Preventive Behaviors among Tuberculosis Patients' Household Contacts During the COVID-19 Pandemic in the Border Areas of Northern Thailand.

The COVID-19 pandemic has exacerbated the rate of tuberculosis (TB) infection among close contacts of TB patients in remote regions. However, research on preventive behaviors, guided by the health belief model (HBM), among household contacts of TB cases is scarce. This study aimed to employ the HBM as a framework to predict TB preventive behaviors among household contacts of TB patients in the border areas of Northern Thailand. A cross-sectional study with multi-stage random sampling was conducted in Chiang Rai Province. The study included 422 TB patients' household contacts aged 18 years or older who had available chest X-ray (CXR) results. A self-administered questionnaire was used to conduct the survey. The participants' mean age was 42.93 years. Pearson correlation analysis showed that TB preventive behavior scores were significantly correlated with TB knowledge (r=0.397), perceived susceptibility (r=0.565), perceived severity (r=0.452), perceived benefits (r=0.581), self-efficacy (r=0.526), and cues to action (r=0.179). Binary logistic regression revealed that the modeled odds of having an abnormal CXR decreased by 30.4% for each 1-point score increase in preventive behavior (OR=0.696; 95% CI, 0.610-0.794). HBM constructs were able to explain preventive behaviors among TB patients' household contacts. The HBM could be used in health promotion programs to improve TB preventive behaviors and avoid negative outcomes.

MR1-restricted T cell clonotypes are associated with resistance to Mycobacterium tuberculosisinfection

Abstract T-cells are a critical facet of the adaptive immune system and have been shown in both human and animal studies to be essential for control of Mycobacterium tuberculosis (Mtb) infection. T-cells recognize foreign antigens presented by infected cells via a unique T-cell receptor (TCR). Understanding the specific TCRs that mediate recognition and clearance of Mtb-infected cells is essential to inform vaccine design. We recently described a cohort of Ugandan household contacts of tuberculosis cases that appear to ‘resist’ Mtb infection (RSTRs) and showed that these individuals harbor IFN-γ independent T-cell responses to Mtb peptide antigens. The role of unconventional T-cells that recognize non-peptide antigens, such as gd T-cells, CD1-restricted and MR1-restricted T-cells (MR1T), in “resistance” is unknown. In this study, we aimed to characterize the frequencies, functional programs, and repertoire of unconventional T-cells in RSTRs in comparison with latently infected (LTBI) controls. We used multi-parameter flow cytometry, single cell RNA and TCR sequencing and immunosequencing to address these gaps. We observed a 1.65-fold increase in frequency of circulating MR1T cells among RSTRs in comparison with LTBI (p=0.03). Single-cell RNA-sequencing of 18,251 sorted MR1T cells revealed 5,150 clonotypes expressing a common transcriptional program, the majority of which were private. Immunosequencing of the TCR-α/d repertoire revealed several TCRα clonotypes that were expanded in RSTRs (p <0.01), including at least two MR1T clonotypes. Overall, our data reveal unexpected donor-specific diversity in the TCR repertoire of human MR1T cells as well as associations between MR1 clonotypes and ‘resistance’ to Mtb infection. This work was supported by grants from the NIH (R01-AI124348 to Boom, Stein, and Hawn; R01-AI125189 and R01-AI146072 to Seshadri) and the Bill & Melinda Gates Foundation (OPP1151836 and OPP1109001 to Hawn and GH-VAP-IS-ID5 to Seshadri).

Household symptomatic contact screening of sputum smear positive tuberculosis patients at the DOTS clinic of SGT hospital, Gurugram

Background: Contact screening was conducted under ICMR (REFERENCE ID: 2019-07811) programme in villages near SGT hospital, Gurugram. Objective: To evaluate risk factors, extent of spread of tuberculosis among household contacts of tuberculosis cases and to create awareness. Methods and Material: Address of TB cases were taken from RNTCP register at DOTS clinic, SGT medical college. Then all household contacts of positive cases were screened, counselled and advised to approach ASHA Workers if such symptoms appear. Data was analysed using appropriate statistical methods. Results:21 Index cases along with 94 household contacts were screened. 61.90% families still use chullahs for cooking. 76.1% families have overcrowding. 3) 61.90% families had inadequate ventilation 4) 19.05%families were aware about the spread of this disease. 5)Only 23.80% families practised adequate sanitation methods and precautions6) 42.8% Index cases had a history of smoking. 7) 44.4% 4 continue to smoke with infection. The association of adequate sanitation with presence of awareness was found to be statistically significant. (p-value<0.05). Other factors were not significantly associated with level of awareness regarding prevention of tuberculosis spread among study participants. Conclusions: Contact screening is an effective tool and it gives the real-time picture of TB in India.

Comparing the Risk of M. Tuberculosis Infection among Men and Women in an African City

Background: Despite the well-known male bias in tuberculosis disease, the underlying reasons remained elusive. We examined whether male predominance in tuberculosis disease is result of higher risk of tuberculosis infection or not. If so, whether it is due to higher likelihood of exposure or higher susceptibility to infection among men. Methods: A household contact study and a prospective cohort study conducted in Kampala, Uganda, from 2013 to 2017 were used to estimate and compare prevalence and annual risk of tuberculosis infection among men and women. In household contact study, index tuberculosis cases and healthy index controls were asked to list their household contacts and extra-household contacts. All contacts were tested with tuberculin skin test to detect tuberculosis infection. In prospective cohort study, individuals with tuberculin skin test (TST) < 5 mm were enrolled and retested with the skin test at one year to detect new infection. Poisson regression with robust standard errors was used to estimate prevalence ratio and relative risk of tuberculous infection between men and women. Results: In household contact study, 123 index tuberculosis cases and 124 index controls listed 382 household contacts of tuberculosis cases, 624 extra-household contacts of tuberculosis cases, and 1044 contacts of controls. Of 1681 enrolled participants in cohort study, 1213 (72%) were retested with TST at one year. There was no sex difference in prevalence of tuberculosis infection among household contacts of tuberculosis cases, but men had a higher prevalence of tuberculosis infection among extra-household contacts of tuberculosis cases (prevalence ratio 1.25, 95% CI 1.06 – 1.48) and contacts of controls (prevalence ratio 1.53, 95% CI 1.30 – 1.81). Similarly, in cohort study, there was no sex difference in annual risk of tuberculosis infection when participant reported knowing tuberculosis cases, but men had a higher annual risk of tuberculosis infection when participants no known contact with tuberculosis (relative risk 1.94, 95% CI: 1.34, 2.80). Conclusion: Men have higher risk of acquiring tuberculous infection than women. Men and women may have the same susceptibility to tuberculosis infection given known exposure to tuberculosis cases. The observed difference in rate of infection may be partially explained by higher rates of exposure to undetected, infectious tuberculosis cases among men.

Vikela Ekhaya: A Novel, Community-based, Tuberculosis Contact Management Program in a High Burden Setting.

BackgroundThe prevention of tuberculosis (TB) in child contacts of TB cases and people living with human immunodeficiency virus (HIV) is a public health priority, but global access to TB preventive therapy (TPT) remains low. In 2019, we implemented Vikela Ekhaya, a novel community-based TB contact management program in Eswatini designed to reduce barriers to accessing TPT.MethodsVikela Ekhaya offered differentiated TB and HIV testing for household contacts of TB cases by using mobile contact management teams to screen contacts, assess their TPT eligibility, and initiate and monitor TPT adherence in participants’ homes.ResultsIn total, 945 contacts from 244 households were screened for TB symptoms; 72 (8%) contacts reported TB symptoms, and 5 contacts (0.5%) were diagnosed with prevalent TB. A total of 322 of 330 (98%) eligible asymptomatic household contacts initiated TPT. Of 322 contacts initiating TPT, 248 children initiated 3 months of isoniazid and rifampicin and 74 children and adults living with HIV initiated 6 months of isoniazid; 298 (93%) completed TPT. In clustered logistic regression analyses, unknown HIV status (adjusted odds ratio [aOR] 5.7, P = .023), positive HIV status (aOR 21.1, P = .001), urban setting (aOR 5.6, P = .006), and low income (aOR 5.9, P = .001) predicted loss from the cascade of care among TPT-eligible contacts.ConclusionVikela Ekhaya demonstrated that community-based TB household contact management is a feasible, acceptable, and successful strategy for TB screening and TPT delivery. The results of this study support the development of novel, differentiated, community-based interventions for TB prevention and control.

Diagnosis of latent tuberculosis infection among pediatric household contacts of Iranian tuberculosis cases using tuberculin skin test, IFN- \u03b3 release assay and IFN-\u03b3-induced protein-10

BackgroundAlthough the World Health Organization has recommended the diagnosis and prophylactic treatment of latent tuberculous infection (LTBI) in child household contacts of tuberculosis (TB) cases, the national programs in high-burden TB regions rarely implement adequate screening of this high-risk group, mainly because of resource limitations. We aimed to evaluate the prevalence of LTBI among pediatric household contacts of TB cases in two high-burden provinces in Iran.MethodsWe conducted a cohort study in children who had been in household contact with a TB index. All subjects were assessed for active TB disease. For LTBI diagnosis, tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were performed at the time of the index TB case diagnosis, as well as, 3, 12, and 18 months, if the first results were negative. In addition, interferon-γ-induced protein-10(IP-10) concentrations were measured for all participants.ResultsA total of 230 children were enrolled, who had contact with an index TB case. Three contacts were diagnosed with active TB. According to the TST/QFT-Plus results, 104 (45.2%) children were identified with LTBI during our study. Significantly increased IP-10 levels were found in LTBI patients compared to healthy contacts. Accordingly, more than 50% of LTBI contacts and about 10% of healthy contacts were considered as IP-10-positive.ConclusionThis study alarmingly illustrates a high prevalence of LTBI among Iranian children exposed to TB cases. We, therefore, emphasize that the children living in close contact with an infectious TB case should be screened effectively and receive prophylactic therapy.

Blood RNA signatures predict recent tuberculosis exposure in mice, macaques and humans

Tuberculosis (TB) is the leading cause of death due to a single infectious disease. Knowing when a person was infected with Mycobacteriumtuberculosis (M.tb) is critical as recent infection is the strongest clinical risk factor for progression to TB disease in immunocompetent individuals. However, time since M.tb infection is challenging to determine in routine clinical practice. To define a biomarker for recent TB exposure, we determined whether gene expression patterns in blood RNA correlated with time since M.tb infection or exposure. First, we found RNA signatures that accurately discriminated early and late time periods after experimental infection in mice and cynomolgus macaques. Next, we found a 6-gene blood RNA signature that identified recently exposed individuals in two independent human cohorts, including adult household contacts of TB cases and adolescents who recently acquired M.tb infection. Our work supports the need for future longitudinal studies of recent TB contacts to determine whether biomarkers of recent infection can provide prognostic information of TB disease risk in individuals and help map recent transmission in communities.

Distinct Risk Factors for Clinical and Bacteriologically Confirmed Tuberculosis among Child Household Contacts in a High-Burden Setting.

The identification and screening of children at high risk of tuberculosis is essential to the control and prevention of child tuberculosis (TB). BUTIMBA, an active case finding and household contact-tracing project implemented between 2013 and 2015 in Eswatini, evaluated 5,413 contacts of 1,568 index cases, of whom 82 (1.5%) were diagnosed with TB disease. We conducted univariate and multivariate clustered logistic regression analyses of risk factors for any TB diagnosis among child household contacts of TB cases. Children younger than 5 years and children with positive HIV status were more likely to have TB than children aged 5-14 years and children with negative HIV status, respectively (adjusted odds ratio [aOR]: 2.2, P < 0.001; aOR: 5.0, P < 0.001). Children with one or more TB symptoms were more likely to be diagnosed with TB based on clinical criteria, but less likely to have bacteriologically confirmed TB, highlighting subjectivity in determination of child TB.

A pragmatic stepped-wedge cluster randomized trial to evaluate the effectiveness and cost-effectiveness of active case finding for household contacts within a routine tuberculosis program, San Juan de Lurigancho, Lima, Peru

BackgroundActive case finding (ACF) in household contacts of tuberculosis (TB) patients is now recommended for National TB Programs (NTP) in low- and middle-income countries. However, evidence supporting these recommendations remains limited. This study evaluates the effectiveness and cost-effectiveness of ACF for household contacts of TB cases in a large TB endemic district of Lima, Peru. MethodsA pragmatic stepped-wedge cluster randomized controlled trial was conducted in 34 health centers of San Juan de Lurigancho district. Centers were stratified by TB rate and randomly allocated to initiate ACF in groups of eight or nine centers at four-month intervals. In the intervention arm, NTP providers visited households of index patients to screen contacts for active TB. The control arm was routine passive case finding (PCF) of symptomatic TB cases. The primary outcomes were the crude and adjusted active TB case rates among household contacts. Program costs were directly measured, and the cost-effectiveness of the ACF intervention was determined. Findings3222 index TB cases and 12,566 household contacts were included in the study. ACF identified more household contact TB cases than PCF, 199.29/10,000 contacts/year vs. 132.13 (incidence rate ratio of 1.51 (95% CI 1.21–1.88)). ACF was associated with an incremental cost-effectiveness ratio of US $16,400 per disability-adjusted life year averted and not cost-effective assuming a willingness-to-pay threshold for Peru of US $6360. ConclusionACF of TB case household contacts detected significantly more secondary TB cases than PCF alone, but was not cost-effective in this setting. In threshold analyses, ACF becomes cost-effective if associated with case detection rates 2.5 times higher than existing PCF programs.

Transmission Modeling with Regression Adjustment for Analyzing Household-based Studies of Infectious Disease: Application to Tuberculosis.

Household contacts of people infected with a transmissible disease may be at risk due to this proximate exposure, or from other unobserved sources. Understanding variation in infection risk is essential for targeting interventions. We develop an analytical approach to estimate household and exogenous forces of infection, while accounting for individual-level characteristics that affect susceptibility to disease and transmissibility. We apply this approach to a cohort study conducted in Lima, Peru, of 18,544 subjects in 4,500 households with at least one active tuberculosis (TB) case and compare the results to those obtained by Poisson and logistic regression. HIV-coinfected (susceptibility hazard ratio [SHR] = 3.80, 1.56-9.29), child (SHR = 1.72, 1.32-2.23), and teenage (SHR = 2.00, 1.49-2.68) household contacts of TB cases experience a higher hazard of TB than do adult contacts. Isoniazid preventive therapy (SHR = 0.30, 0.21-0.42) and Bacillus Calmette-Guérin (BCG) vaccination (SHR = 0.66, 0.51-0.86) reduce the risk of disease among household contacts. TB cases without microbiological confirmation exert a smaller hazard of TB among their close contacts compared with smear- or culture-positive cases (excess hazard ratio = 0.88, 0.82-0.93 for HIV- cases and 0.82, 0.57-0.94 for HIV+ cases). The extra household force of infection results in 0.01 (95% confidence interval [CI] = 0.004, 0.028) TB cases per susceptible household contact per year and the rate of transmission between a microbiologically confirmed TB case and susceptible household contact at 0.08 (95% CI = 0.045, 0.129) TB cases per pair per year. Accounting for exposure to infected household contacts permits estimation of risk factors for disease susceptibility and transmissibility and comparison of within-household and exogenous forces of infection.

Factors associated with tuberculosis disease among children who are household contacts of tuberculosis cases in an urban setting in Malaysia

BackgroundWith the rise in prevalence of childhood tuberculosis (TB) globally, contact tracing should be a powerful strategy for early diagnosis and management, especially in children who are household contacts of active TB cases. Here, we aimed to determine the prevalence and factors associated with TB disease in children who are household contacts of TB cases.MethodsWe used a cross-sectional study with data from the Malaysian TB Information System (TBIS) recorded from 1 January 2014 to 31 December 2017. All children aged 0–14 years who were registered in the TBIS with at least one household contact of TB cases were included in the study. Multiple logistic regression analysis was performed to calculate the adjusted odds ratio (adj. OR) and for adjusting the confounding factors.ResultsA total of 2793 children were included in the study. The prevalence of active TB was 1.5% (95% confidence interval [CI]: 1.31, 1.77%). Children aged < 5 years [adj. OR 9.48 (95% CI: 3.41, 26.36) p < 0.001] with positive tuberculin skin test [adj. OR 395.73 (95% CI: 134.17, 1167.13), p < 0.001] and investigation period of > 6 weeks [adj. OR 7.48 (95% CI: 2.88, 19.43), p < 0.001] had significantly higher odds for TB disease.ConclusionsThe prevalence of TB disease in children who were household contacts of TB cases is relatively low. However, contact tracing programmes should not only focus on children aged < 5 years and with positive tuberculin skin test results, but also be empowered to reduce the investigation period.

Implementation of screening and management of household contacts of tuberculosis cases in Daru, Papua New Guinea.

Daru Island, Western Province, Papua New Guinea (PNG). To describe the implementation of a screening programme for household contacts of tuberculosis (TB) cases residing on Daru Island. This was a retrospective descriptive study evaluating two periods of implementation: introduction and expansion of a screening programme for household contacts of drug-resistant TB (DR-TB) cases (March 2016 to September 2017), and inclusion of drug-susceptible TB (DS-TB) cases with provision of preventive therapy for eligible contacts between October 2017 and March 2018. In the first period, the contact screening programme was established and strengthened by increasing coverage over time. There was a large number of contacts (median 8) in each household, and a high uptake of screening. In the second period of evaluation, respectively 412 and 223 contacts of 42 DS-TB and 25 DR-TB index cases were screened. Overall, 156 (24.6%) contacts reported TB-related symptoms and 9 (1.4%) were diagnosed with active TB. All 9 commenced TB treatment: 5 had DS-TB and 4 had DR-TB. Of 82 child contacts of DS-TB cases eligible for preventive therapy, 57 (69.5%) commenced treatment and 45 completed treatment. Community-based household contact screening and management was successfully implemented under programme conditions in this high burden TB and DR-TB setting in PNG.

Hot and Cold Spot Areas of Household Tuberculosis Transmission in Southern China: Effects of Socio-Economic Status and Mycobacterium tuberculosis Genotypes.

The aims of the study were: (1) compare sociodemographic characteristics among active tuberculosis (TB) cases and their household contacts in cold and hot spot transmission areas, and (2) quantify the influence of locality, genotype and potential determinants on the rates of latent tuberculosis infection (LTBI) among household contacts of index TB cases. Parallel case-contact studies were conducted in two geographic areas classified as “cold” and “hot” spots based on TB notification and spatial clustering between January and June 2018 in Guangxi, China, using data from field contact investigations, whole genome sequencing, tuberculin skin tests (TSTs), and chest radiographs. Beijing family strains accounted for 64.6% of Mycobacterium tuberculosis (Mtb) strains transmitted in hot spots, and 50.7% in cold spots (p-value = 0.02). The positive TST rate in hot spot areas was significantly higher than that observed in cold spot areas (p-value < 0.01). Living in hot spots (adjusted odds ratio (aOR) = 1.75, 95%, confidence interval (CI): 1.22, 2.50), Beijing family genotype (aOR = 1.83, 95% CI: 1.19, 2.81), living in the same room with an index case (aOR = 2.29, 95% CI: 1.5, 3.49), travelling time from home to a medical facility (aOR = 4.78, 95% CI: 2.96, 7.72), history of Bacillus Calmette-Guérin vaccination (aOR = 2.02, 95% CI: 1.13 3.62), and delay in diagnosis (aOR = 2.56, 95% CI: 1.13, 5.80) were significantly associated with positive TST results among household contacts of TB cases. The findings of this study confirmed the strong transmissibility of the Beijing genotype family strains and this genotype’s important role in household transmission. We found that an extended traveling time from home to the medical facility was an important socioeconomic factor for Mtb transmission in the family. It is still necessary to improve the medical facility infrastructure and management, especially in areas with a high TB prevalence.

Early Clearance of Mycobacterium tuberculosis Is Associated With Increased Innate Immune Responses.

A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed "early clearance." Indonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive. Among 1347 case contacts, 317 were early clearers and 116 were converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA-negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA-negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae. Early clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.

Challenges in the Estimation of the Annual Risk of Mycobacterium tuberculosis Infection in Children Aged Less Than 5 Years.

Accurate estimates of Mycobacterium tuberculosis infection in young children provide a critical indicator of ongoing community transmission of M. tuberculosis. Cross-reactions due to infection with environmental mycobacteria and/or bacille Calmette-Guérin (BCG) vaccination compromise the estimates derived from population-level tuberculin skin-test surveys using traditional cutoff methods. Newer statistical approaches are prone to failure of model convergence, especially in settings where the prevalence of M. tuberculosis infection is low and environmental sensitization is high. We conducted a tuberculin skin-test survey in 5,119 preschool children in the general population and among household contacts of tuberculosis cases in 2012–2014 in a district in northern Malawi where sensitization to environmental mycobacteria is common and almost all children are BCG-vaccinated. We compared different proposed methods of estimating M. tuberculosis prevalence, including a method described by Rust and Thomas more than 40 years ago. With the different methods, estimated prevalence in the general population was 0.7%–11.5% at ages <2 years and 0.8%–3.3% at ages 2–4 years. The Rust and Thomas method was the only method to give a lower estimate in the younger age group (0.7% vs 0.8%), suggesting that it was the only method that adjusted appropriately for the marked effect of BCG-attributable induration in the very young.

IPT uptake among child contacts of TB patients: Experience from the Indus Hospital TB program, Karachi, Pakistan

BackgroundInfants and young children are particularly susceptible to developing tuberculosis (TB) following exposure and infection, and isoniazid preventive therapy can substantially reduce this risk. This evidence-base provides the rationale for the policy and guidelines to screen and manage children that are household contacts of TB cases, prioritizing those with sputum smear-positive TB. The guidelines have been in place for decades, but are rarely implemented. IPT programs in high-TB burden countries are rare and fraught with low uptake and low rates of therapy completion. MethodsThis study describes the demographics and outcomes of contact management and the IPT program for <5years old at the Indus Hospital in Karachi, Pakistan from 2011 to 2014. Children <5years old in contact with newly diagnosed sputum smear-positive pulmonary TB patients were referred by the counselor for contact evaluation. All children underwent a history, physical, CXR and TST. All contacts were started on IPT based on WHO recommendations after confirming that they had no TB disease. Outcomes were defined as children who were enrolled, started on IPT but never returned for follow-up (primary default), children who had one or more follow-up visits but did not complete treatment (default) and children who completed IPT (treatment completed). ResultsA total of 240 children were enrolled in the Indus IPT program from 2011 to 2014. Of these, data from 184 contacts was analyzed in detail as the remainder were still on IPT. All children enrolled were less than 5years of age (mean age 3years) and 96 (52%) were males. Of all the enrolled children, 76/240 (31.6%) were <5% weight for their age (underweight), of these 52% were female children. A symptom of either cough or fever was reported by 29/184 (15.7%) children; however, all responded to routine antibiotics and did not have CXR findings suggestive of TB disease. Of the enrolled who had a TST done, 12/209 (5.8%) had a positive result. Analysis of outcomes revealed that only 60/184 (32.6%) completed 6months of IPT (with no gender predisposition). Among those who completed therapy, none developed TB disease during follow-up. Outcome trends revealed an increase in completion rate (40% in 2013 compared with 26% in 2012), which may reflect improvement in counseling services in 2013. Children who had an initial symptom or were underweight at the start of IPT were more likely to complete treatment (p<0.01). ConclusionDespite a large cohort of TB patients in the Indus TB program-5487 SS+ patients registered during the study period – this IPT program enrollment has been low. A high rate of patient default after the first visit indicates a lack of understanding about the benefit and safety of preventive therapy in young children among families of TB patients, and awareness enhancing efforts by community field teams will help improve outcomes. It is vital that the National TB Program strengthens and expands contact management with a community-based approach and incentives.

Contact investigation of children exposed to tuberculosis in South East Asia: a systematic review.

Background. Screening of children who are household contacts of tuberculosis (TB) cases is universally recommended but rarely implemented in TB endemic setting. This paper aims to summarise published data of the prevalence of TB infection and disease among child contacts in South East Asia. Methods. Search strategies were developed to identify all published studies from South East Asia of household contact investigation that included children (0–15 years). Results. Eleven studies were eligible for review. There was heterogeneity across the studies. TB infection was common among child contacts under 15 years of age (24.4–69.2%) and was higher than the prevalence of TB disease, which varied from 3.3% to 5.5%. Conclusion. TB infection is common among children that are household contacts of TB cases in South East Asia. Novel approaches to child contact screening and management that improve implementation in South East Asia need to be further evaluated.

Identifying recent Mycobacterium tuberculosis transmission in the setting of high HIV and TB burden

BackgroundAccurate diagnosis of latent tuberculosis infection (LTBI) in recently exposed HIV-infected tuberculosis (TB) contacts is a public health priority because of the high risk of progression to active TB but...