Household Contacts Of Tuberculosis Patients Research Articles

First insight into latent tuberculosis infection among household contacts of tuberculosis patients in Duhok, Iraqi Kurdistan: using tuberculin skin test and QuantiFERON-TB Gold Plus test

BackgroundThe objectives were to estimate the prevalence of latent tuberculosis infection (LTBI) among household contacts (HHCs) with active TB patients, and to identify their risk factors. MethodsA prospective, cross sectional study was conducted from May to October 2018. All HHCs with active TB cases were included. The subjects underwent two tests: Quantiferon TB-Gold plus assay (QFT-Plus) and tuberculin skin test (TST). Data were analyzed using the Statistical Package for Social Sciences 25. ResultsAmong 521 HHCs, 101 (24.05%) revealed positive TST and 80 (19.85%) positive QFT-Plus. The significant risk factors associated with positive TST individuals were ≥ 15 years, immunosuppressive therapy, and pulmonary TB (PTB) patients; whereas, those with QFT-Plus positive were ≥ 45 years, alcohol consumption, and immunosuppressive therapy. The concordance rate among 309 individuals who performed both tests was 0.88 %; the kappa value showed good agreement (k = 0.679) and significant correlation (P < 0.001). ConclusionsThe overall rate of LTBI was intermediate. Screening of LTBI should be routine among HHCs, regardless of the site of the disease. Age ≥ 15 years, alcoholics, immunosuppressive therapy, and PTB were potential risk factors. There was a good concordance between TST and QFT-Plus. A QFT-Plus can overcome the limitation of a BCG vaccinated individual, especially in early life.

Contact evaluation and isoniazid preventive therapy among close and household contacts of tuberculosis patients in Lima, Peru: an analysis of routine data

Contacts of pulmonary tuberculosis (TB) cases are at high risk of TB infection and progression to disease. Close and household contacts and those <5years old have the highest risk. Isoniazid preventive therapy (IPT) can largely prevent TB disease among infected individuals. International and Peruvian recommendations include TB contact investigation and IPT prescription to eligible contacts. We conducted a study in Lima, Peru, to determine the number of close and household contacts who were evaluated, started on IPT, and who completed it, and the factors associated to compliance with national guidelines. We conducted a longitudinal retrospective study including all TB cases diagnosed between January 2015 and July 2016 in 13 health facilities in south Lima. Treatment cards, TB registers and clinical files were reviewed and data on index cases (sex, age, smear status, TB treatment outcome), contact investigation (sex, age, kinship to the index case, evaluations at month 0, 2 and 6) and health facility (number of TB cases notified per year, proportion of TB cases with treatment success) were extracted. We tabulated frequencies of contact evaluation by contact and index case characteristics. To investigate determinants of IPT initiation and completion, we used generalised linear mixed models. A total of 2323 contacts were reported by 662 index cases; the median number of contacts per case was four (IQR, 2-5). Evaluation at month 0 was completed by 99.2% (255/257) of contacts <5 and 98.1% (558/569) of contacts aged 5-19years. Of 191 eligible contacts <5years old, 70.2% (134) started IPT and 31.4% (42) completed it. Of 395 contacts 5-19years old, 36.7% (145) started IPT and 32.4% (47) completed it. Factors associated to not starting IPT among contacts <5years old were being a second-degree relative to the index case (OR 6.6 95CI% 2.6-16.5), not having received a tuberculin skin test (TST) (OR 3.9 95%CI 1.4-10.8), being contact of a smear-negative index case (OR 5.5 95%CI 2.0-15.1) and attending a low-caseload health facility (OR 2.8 95%CI 1.3-6.2). Factors associated to not starting IPT among 5-19year-olds were age (OR 13.7 95%CI 5.9-32.0 for 16-19 vs. 5-7years old), being a second-degree relative (OR 3.0 95%CI 1.6-5.6), not having received a TST (OR 5.4, 95%CI 2.5-11.8), being contact of a male index case (OR 2.1 95CI% 1.2-3.5), with smear-negative TB (OR 1.9 95%CI 1.0-3.6), and attending a high-caseload health facility (OR 2.1 95%CI 1.2-3.6). Factors associated to not completing IPT, among contacts who started, were not having received a TST (OR 3.4 95%CI 1.5-7.9 for <5year-olds, and OR 4.3 95%CI 1.7-10.8 for those 5-19years old), being contact of an index case with TB treatment outcome other than success (OR 9.3 95%CI 2.6-33.8 for <5year-olds and OR 15.3 95%CI 1.9-125.8 for those 5-19years old), and, only for those 5-19years old, attending a health facility with high caseload (OR 3.2 95%CI 1.4-7.7) and a health facility with low proportion of TB cases with treatment success (OR 4.4 95%CI 1.9-10.2). We found partial compliance to TB contact investigation, and identified contact, index case and health facility-related factors associated to IPT start and completion that can guide the TB programme in increasing coverage and quality of this fundamental activity.

What Proportion of New Tuberculosis Patients Has a History of Household Tuberculosis Exposure? A Cross-Sectional Study from Udupi District, South India.

While tuberculosis (TB) preventive therapy among household contacts is effective at an individual level, its population-level impact on reducing TB incidence has been unclear. In this study, we aimed to assess, among the new tuberculosis patients started on treatment between 1 October, 2018 and 30 June, 2019 in the public health facilities of Udupi district (South India): i) the proportion with a ‘history of household TB exposure’ and ii) sociodemographic and clinical factors associated with it. We conducted a cross-sectional study involving record review and patient interviews. Of 565 TB patients, 273(48%) were interviewed. Of them, 71(26%, 95% CI: 21%–32%) patients had a ‘history of household TB exposure (ever)’ with about half exposed in the past five years of diagnosis. Considering a new TB case as a proxy for incident TB, and ‘history of household TB exposure’ a proxy for household transmission, and assuming 100% effectiveness of preventive therapy, we may infer that a maximum of 26% of the incident cases can be prevented by giving preventive therapy to all household contacts of TB patients. In multivariable analysis, females and tobacco users had a significantly higher prevalence of household TB exposure. If there are resource constraints, these subgroups may be prioritized.

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

BackgroundFew 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 findingsWe 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.ConclusionOur 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.

Serial T-SPOT.TB in household contacts of tuberculosis patients: a 6-year observational study in China.

BACKGROUND: Screening tuberculosis (TB) contacts is a priority for TB control; however, it remains inadequate in most regions of China.OBJECTIVE: To investigate the progression of latent TB infection (LTBI) using the interferon-gamma release assay (IGRA) in contacts of active TB patients.DESIGN: This longitudinal prospective observational study included 159 household contacts aged ≥14 years without preventive treatment who were followed up for 6 years to compare their conversion and reversion rates using the T-SPOT®.TB IGRA to diagnose LTBI.RESULTS: Among the 159 household contacts, LTBI positivity was 47.5%. Age was independently associated with LTBI (OR 3.6, 95%CI 1.81-7.14; P = 0.00). T-SPOT.TB conversion rates were respectively 29.4% and 18.8% at 3- and 6-year follow-up. The reversion rates were 9.4% of contacts during the 3-year follow-up period, which increased to 38.2% at the 6-year follow-up. A decreasing trend in spot-forming cells on T-SPOT.TB was observed in most patients at the 6-year follow-up.CONCLUSION: LTBI prevalence among household contacts was relatively high, particularly in elderly patients. Furthermore, serial IGRA testing was highly dynamic; however, this overall trend gradually decreased over time, even if preventive therapy was not prescribed.

Optimizing the efficiency of tuberculosis active case-finding in health facilities and communities.

SETTING: Efficient tuberculosis (TB) active case-finding strategies are important in settings with high TB burdens and limited resources, such as those in western Kenya.OBJECTIVE: To guide efforts to optimize screening efficiency, we identified the predictors of TB among people screened in health facilities and communities.DESIGN: During February 2015-June 2016, adults aged ≥15 years reporting any TB symptom were identified in health facilities and community mobile screening units, and evaluated for TB. We assessed the predictors of TB using a modified Poisson regression with generalized estimating equations to account for clustering according to screening site.RESULTS: TB was diagnosed in 484 (20.3%) of 2394 symptomatic adults in health facilities and 39 (3.4%) of 1424 in communities. In health facilities, >10% of symptomatic adults in all demographic groups had TB, and no predictors were associated with a ≥2-fold increased risk. In communities, the independent predictors of TB were male sex (adjusted prevalence ratio [aPR] = 4.26, 95%CI 2.43-7.45), HIV infection (aPR 2.37, 95%CI 1.18-4.77), and household TB contact in the last 2 years (aPR 2.84, 95%CI 1.62-4.96).CONCLUSION: Our findings support the notion of general TB screening in health facilities and evaluation of the adult household contacts of TB patients.

Tuberculosis household accompaniment to improve the contact management cascade: A prospective cohort study.

BackgroundAppropriate management of people exposed in the home to tuberculosis is essential to prevent morbidity. These household contacts, particularly children, should receive preventive therapy to prevent them from falling ill. However, few people receive preventive therapy worldwide. We sought to determine whether a community-based accompaniment intervention could improve tuberculosis contact management.MethodsWe conducted a prospective cohort study of household contacts of tuberculosis patients who initiated treatment during September 2015-June 2016 in Lima, Peru. Enrolled households received an intervention comprising home visits, transport vouchers, assistance coordinating evaluation procedures, and adherence support during preventive therapy. To evaluate the impact of the intervention, we conducted retrospective chart reviews of all patients initiating treatment during 6-month baseline and intervention periods.ResultsWe enrolled 314 household contacts of 109 index patients. Of these, 283 (90%) completed evaluation, and 4 (1%) were diagnosed with tuberculosis. Preventive therapy was prescribed for 35/38 (92%) contacts 0–19 years old who were eligible under Peruvian guidelines. Preventive therapy was also prescribed for 6/26 (23%) contacts with unknown eligibility due to lack of a tuberculin skin test (TST), and 20/69 (29%) who were ineligible either because of a negative TST result or exposure to a drug-resistant or extrapulmonary case. Of the 61 contacts who were prescribed preventive therapy, 57 (93%) initiated treatment, and 51 (91%) completed treatment. The proportion of contacts who completed evaluation increased from 42% during the baseline period to 71% during the evaluation period (risk ratio [RR] = 1.73, 95% confidence interval [95% CI]: 1.41–2.13). The proportion of contacts who initiated preventive therapy increased from 15% to 40% (RR = 2.45, 95% CI: 1.42–4.22).ConclusionAccompaniment of TB patient households greatly improved the evaluation of household contacts for TB and increased the use of preventive therapy.

Myths and realities about knowledge, attitudes and practices of household contacts of tuberculosis patients.

Five Colombian cities: Villavicencio, Pereira, Cucuta, Bucaramanga and Bosa. To describe the knowledge, attitudes and practices related to tuberculosis (TB) in household contacts (HHCs) of TB patients. A cross-sectional study was conducted. The estimated sample size required was 855. The World Health Organization guide 'Advocacy, communication and social mobilization for TB control: a guide to developing knowledge, attitude and practice surveys' was translated into Spanish and adapted to the dialect of each city. HHCs were invited to participate in the study and included if they agreed. We interviewed 878 HHCs. Most of them knew that TB was transmitted by airborne droplets; however, 52.2% also said that TB could be transferred from one person to another by sharing plates or clothes or shaking hands. Fifty-five per cent of HHCs acquired TB-related information from health care workers, and 44% from family members and friends. Fear was the main reaction reported by HHCs when they were informed of a TB diagnosis (60%). Eighty-five per cent of HHCs answered that the community rejects or avoids TB cases. There are significant gaps in the knowledge about TB and the stigmatisation associated with it. Educational strategies should be designed together with the community to demystify many misconceptions about TB.

Diabetes and pre-diabetes among household contacts of tuberculosis patients in India: is it time to screen them all?

Pre-diabetes mellitus (pre-DM) and DM increase the risk of developing tuberculosis (TB). Screening contacts of TB patients for pre-DM/DM and linking them to care may mitigate the risk of developing TB and improve DM management. To measure the prevalence of pre-DM/DM and associated factors among the adult household contacts (HHCs) of pulmonary TB patients. Between August 2014 and May 2017, adult HHCs of newly diagnosed adult PTB patients in Pune and Chennai, India, had single blood samples tested for glycosylated haemoglobin (HbA1c) at enrolment. DM was defined as previously diagnosed, self-reported DM or HbA1c 6.5%, and pre-DM as HbA1c between 5.7% and 6.4%. Latent tuberculous infection (LTBI) was defined as a positive tuberculin skin test (5 mm induration) or QuantiFERON® Gold In-Tube (0.35 international units/ml). Of 652 adult HHCs, 175 (27%) had pre-DM and 64 (10%) had DM. Forty (64%) HHCs were newly diagnosed with DM and 48 (75%) had poor glycaemic control (HbA1c 7.0%). Sixty-eight (22%) pre-DM cases were aged 18-34 years. Age 35 years, body mass index 25 kg/m2, chronic disease and current tobacco smoking were significantly associated with DM among HHCs. Adult HHCs of TB patients in India have a high prevalence of undiagnosed DM, pre-DM and LTBI, putting them at high risk for developing TB. Routine DM screening should be considered among all adult HHCs of TB.

Yield of tuberculosis among household contacts of tuberculosis patients in Accra, Ghana

BackgroundThe End TB Strategy calls for systematic screening of selected high-risk groups including contacts of tuberculosis (TB) cases to facilitate early TB case detection. Contact investigation is not usually routinely practiced in low TB burden countries, such as Ghana, with consequent paucity of data on the yield of TB case detection from such interventions. This study’s objective was to document the outcomes and feasibility of implementing contact investigation activities under programmatic conditions in Ghana.MethodsRetrospective analyses were conducted of abstracted data from the National TB Program, following a contact investigation intervention for TB cases diagnosed in 10 facilities in Accra from June 2010 to December 2014. Various proportions and yield from number of contacts needed to screen (NNS) and number needed to test (NNT) to detect a TB case were assessed.ResultsOverall, out of the 8519 listed contacts of 3267 index cases, 8166 (96%) were screened and 614 (7.5%) were identified as presumptive TB. Out of these, 438 (71%) underwent sputum smear microscopy/evaluation and 53 TB cases were diagnosed. Of these, 56.6% were males, and 49% had sputum smear-positive TB, 38% had sputum smear-negative TB, and 7% had extra-pulmonary TB. The NNS and NNT to detect a TB case of all forms were 154 and 8, respectively. The proportion of TB cases with contacts listed and proportion of contacts screened annually were 88–96% and 83–100%, respectively. The proportion of presumptive TB cases tested and proportion of TB cases diagnosed among contacts tested that were 100% and 36%, respectively, in 2010 dropped to 40% and 14%, respectively, by 2014.ConclusionsThe study demonstrates that contact identification and prioritization components of a contact investigation were feasible, but overall yield of TB cases may have been lower due to the declining rate of clinical evaluation of presumptive TB contacts over time. Addressing barriers to accessing appropriate diagnostic tests may enhance yield from contact investigation in Ghana.

Transcriptional networks are associated with resistance to Mycobacterium tuberculosis infection.

RationaleUnderstanding mechanisms of resistance to M. tuberculosis (M.tb) infection in humans could identify novel therapeutic strategies as it has for other infectious diseases, such as HIV.ObjectivesTo compare the early transcriptional response of M.tb-infected monocytes between Ugandan household contacts of tuberculosis patients who demonstrate clinical resistance to M.tb infection (cases) and matched controls with latent tuberculosis infection.MethodsCases (n = 10) and controls (n = 18) were selected from a long-term household contact study in which cases did not convert their tuberculin skin test (TST) or develop tuberculosis over two years of follow up. We obtained genome-wide transcriptional profiles of M.tb-infected peripheral blood monocytes and used Gene Set Enrichment Analysis and interaction networks to identify cellular processes associated with resistance to clinical M.tb infection.Measurements and main resultsWe discovered gene sets associated with histone deacetylases that were differentially expressed when comparing resistant and susceptible subjects. We used small molecule inhibitors to demonstrate that histone deacetylase function is important for the pro-inflammatory response to in-vitro M.tb infection in human monocytes.ConclusionsMonocytes from individuals who appear to resist clinical M.tb infection differentially activate pathways controlled by histone deacetylase in response to in-vitro M.tb infection when compared to those who are susceptible and develop latent tuberculosis. These data identify a potential cellular mechanism underlying the clinical phenomenon of resistance to M.tb infection despite known exposure to an infectious contact.

TST positivity in household contacts of tuberculosis patients: a case-contact study in Malawi

BackgroundScreening household contacts of active tuberculosis (TB) patients is recommended for TB control. Due to resource constraints this rarely occurs in lower income countries. Demographic and clinical features of index cases may influence the likelihood of onwards TB transmission. It has also been proposed that accumulation of intracellular lipid bodies within M. tuberculosis cells may also enhance bacterial transmissibility. This study explored whether clinical and bacteriological observations recorded at baseline in TB cases in Malawi could help identify those with the highest risk of onwards transmission, to prioritise contact tracing.MethodsIn this case-contact study, data on clinical presentation, sputum bacterial load and the percentage of lipid body positive acid-fast bacilli (%LB + AFB) on sputum smears were recorded in adults with sputum smear and culture positive pulmonary TB before initiation of therapy. The Tuberculin Skin Test (TST) was used to detect infection with M. tuberculosis amongst household contacts under the age of 15 years. TST positivity of the child contacts was related to characteristics of the index case.ResultsThirty four index cases brought 56 contacts (median: 1, range: 1–4 contacts each). 37 (66%) of contacts had a positive TST. Cavities or a high percentage of lung affected on index patient CXRs were associated with TST positivity. Multivariate analysis of non-radiological factors showed that male sex, HIV-negative status and raised peripheral blood white blood count (WBC) in index patients were also independent risk factors of TST positivity. Lower %LB + AFB counts were associated with TST positivity on univariate analysis only.ConclusionTST positivity is common amongst household contacts of sputum smear positive adult TB patients in Malawi. Contact tracing in this high risk population could be guided by prioritising index cases with CXR cavities and extensive radiological disease or, in the absence of CXRs, those who are HIV-negative with a raised WBC.

A randomized controlled study of socioeconomic support to enhance tuberculosis prevention and treatment, Peru.

ObjectiveTo evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients.MethodsA non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru’s national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms.FindingsOverall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1–4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0–2.6). These improvements were equitable, being independent of household poverty.ConclusionA tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.

Diverse Pattern of Cytokine Production, their Functional Association and mRNA Expression in Tuberculosis Patients with Diabetes Mellitus and their Household Contacts

Cytokine genes are associated with their altered production and play a significant role in tuberculosis patients with diabetes mellitus and their household contacts. We aimed to study the influence of IL-1β and IL-6 gene polymorphisms on cytokine gene production and to evaluate their mRNA expression in M.tbAg85A stimulated culture supernatants of tuberculosis patients with diabetes mellitus, pulmonary tuberculosis patients, household contacts and diabetes individuals. Enzyme linked immunosorbent assay was used to estimate cytokine production in the culture supernatants and TRIZOL method for mRNA expression. Cytokine production was low in all the subjects when compared to the healthy controls and IL-6 levels increased with treatment. The CC genotype of IL-6 -174 G/C was associated with its low production in household contacts of tuberculosis patients with diabetes mellitus and pulmonary tuberculosis patients. The mRNA expression of IL-1β increased and that of IL-6 decreased in tuberculosis patients with diabetes mellitus, while that of IL-6 decreased with treatment in pulmonary tuberculosis patients; however, there was no significant difference in the household contacts. The cytokine levels were almost similar in patients and their household contacts at the time of diagnosis suggesting that even the household contacts might be infected thus aiding in protecting the high-risk individuals by their prior identification.

Low tuberculosis case detection: a community and health facility based study of contributory factors in the Nkwanta South district of Ghana.

BackgroundTuberculosis (TB) continues to pose a major public health problem globally. In Ghana, the national TB case detection rate is 81 %; however, some districts are not able to meet their case detection targets. This study was therefore carried out in the Nkwanta South district to identify possible factors contributing to low TB case detection.MethodsA cross sectional descriptive study involving the review of outpatients records for the year 2012 was conducted. Data on cough for 2 weeks or more duration, age, sex, area of residence and sputum smear examination were extracted. A community-based survey involving household contacts of TB patients and community based volunteers was also carried out. Data collected in the community included knowledge of TB status of relatives, level of socialization with TB patients and signs and symptoms of TB disease. Descriptive statistics including cross-tabulations were used to identify possible factors contributing to low TB case detection.ResultsA total of 932 patients out of 3987 reported coughing for 2 weeks or more (23.4 %; 932/3987). Out of that, only 24.6 % (230/932) had sputum smear microscopy done, yielding 57 (24.8 %) positive cases. Five out of the 57 positive cases were found not registered for the initiation of treatment leading to a false primary default rate of 8.8 % per year. Eighty-five percent of the contacts were able to mention persistent cough as a sign/symptom of TB with 80.4 % indicating that TB can be cured. Only 10 % of health facilities provided diagnostic services in the district with only 25 % of staff having had training in TB management.ConclusionThe study identified some factors (weak record review systems, inadequate diagnostic centres, lack of trained persons and some level of stigma at the community level) that could be contributing to low TB case detection in the Nkwanta South district.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-2136-x) contains supplementary material, which is available to authorized users.

Cytokine production and mRNA expression in pulmonary tuberculosis patients and their household contacts of younger age group (15–25 years)

Household contacts of tuberculosis patients are at high risk of infection and development of active disease. In this study we evaluated the cytokine production and mRNA expression of IFN-γ, TNF-α, IL-10&IL-6 stimulated with r32kDa M. bovis BCGAg in active pulmonary tuberculosis patients (APTB), household contacts (HHC) and healthy controls (HC). The results showed the stimulated levels of IFN-γ and TNF-α were low while IL-10 levels were high in APTB and HHC compared to HC. IL-6 has not shown any significant difference. The mRNA expression of TNF- α was 8 fold high in HCs compared to APTB and HHC. The IL-6 expression was 2.2 fold &1 fold less in APTB and HHC compared to HCs. Multinomial logistic regression analysis indicated that the stimulated levels of IFN-γ & IL-6 and sex significantly predicted the HHC group from HCs at p<0.05.In conclusion further follow up studies with r32kd antigen might help to identify the high risk individuals.

Impact of Co-Infections and BCG Immunisation on Immune Responses among Household Contacts of Tuberculosis Patients in a Ugandan Cohort

BackgroundTuberculosis incidence in resource poor countries remains high. We hypothesized that immune modulating co-infections such as helminths, malaria, and HIV increase susceptibility to latent tuberculosis infection (LTBI), thereby contributing to maintaining the tuberculosis epidemic.MethodsAdults with sputum-positive tuberculosis (index cases) and their eligible household contacts (HHCs) were recruited to a cohort study between May 2011 and January 2012. HHCs were investigated for helminths, malaria, and HIV at enrolment. HHCs were tested using the QuantiFERON-TB Gold In-Tube (QFN) assay at enrolment and six months later. Overnight whole blood culture supernatants from baseline QFN assays were analyzed for cytokine responses using an 11-plex Luminex assay. Associations between outcomes (LTBI or cytokine responses) and exposures (co-infections and other risk factors) were examined using multivariable logistic and linear regression models.ResultsWe enrolled 101 index cases and 291 HHCs. Among HHCs, baseline prevalence of helminths was 9% (25/291), malaria 16% (47/291), HIV 6% (16/291), and LTBI 65% (179/277). Adjusting for other risk factors and household clustering, there was no association between LTBI and any co-infection at baseline or at six months: adjusted odds ratio (95% confidence interval (CI); p-value) at baseline for any helminth, 1.01 (0.39–2.66; 0.96); hookworm, 2.81 (0.56–14.14; 0.20); malaria, 1.06 (0.48–2.35; 0.87); HIV, 0.74 (0.22–2.47; 0.63). HHCs with LTBI had elevated cytokine responses to tuberculosis antigens but co-infections had little effect on cytokine responses. Exploring other risk factors, Th1 cytokines among LTBI-positive HHCs with BCG scars were greatly reduced compared to those without scars: (adjusted geometric mean ratio) IFNγ 0.20 (0.09–0.42), <0.0001; IL-2 0.34 (0.20–0.59), <0.0001; and TNFα 0.36 (0.16–0.79), 0.01.ConclusionsWe found no evidence that co-infections increase the risk of LTBI, or influence the cytokine response profile among those with LTBI. Prior BCG exposure may reduce Th1 cytokine responses in LTBI.

Age-specific risks of tuberculosis infection from household and community exposures and opportunities for interventions in a high-burden setting.

We analyzed data from a large population-based prospective cohort study of household contacts of tuberculosis patients in Lima, Peru, to estimate the importance of within-household transmission relative to community-based transmission. We identified all adults (older than 15 years of age) who had incident pulmonary tuberculosis diagnosed at any of 106 public health centers in Lima from September 2009 to August 2012. A total of 14,041 household contacts of 3,446 index patients were assessed for tuberculosis infection and disease. We compared the prevalence of latent tuberculosis infection (LTBI) among persons who had received the Bacillus Calmette-Guérin vaccine in households with and without a microbiologically confirmed index case to estimate the age-specific risk of infection and excess risk of LTBI from household and community exposures. We found that the risk of infection from household and community sources increased from birth until 20 years of age. However, a large proportion of infections among child and young-adult household contacts could have been the result of household exposure. Excess infection risk associated with household exposure accounted for 58% (95% confidence interval: 47, 66) of LTBI prevalence among exposed children younger than 1 year of age, 48% (95% confidence interval: 39, 57) among 10-year-old children, and 44% (95% confidence interval: 34, 51) among 15-year-old adolescents. These findings suggest that expanded access to preventive therapy for older children and young-adult household contacts of known tuberculosis cases may be beneficial.

Tuberculosis burden in China: a high prevalence of pulmonary tuberculosis in household contacts with and without symptoms

BackgroundIn the context of decreasing tuberculosis prevalence in China, we examined the effectiveness of screening household contacts of tuberculosis patients.MethodsA tuberculosis survey was conducted in 2008. All 3,355 household contacts of notified tuberculosis cases were examined with a questionnaire interview, chest X-ray and three sputum smear tests. The effectiveness was examined by comparing the prevalence of pulmonary tuberculosis in household contacts with or without presenting clinical symptoms against the respective notification rates. Regression models were used to evaluate the factors associated with pulmonary tuberculosis.ResultsOf the 3,355 household contacts, 92 members (2.7%) had pulmonary tuberculosis, among which 46 cases were asymptomatic. The prevalence of pulmonary tuberculosis and smear positive cases in household contacts without symptoms were 20 and 7 times higher than the notification rates in 2008, while those in household contacts with symptoms were 247 and 108 times higher than notification rates, respectively. The patients detected were mainly Index Cases’ spouses, sisters/brothers and those who were in contact with female Index Cases.ConclusionsThe present study provides convincing evidence that household contacts of notified tuberculosis cases are at higher risk of developing tuberculosis. Routine screening for household contacts without any symptoms is recommended for sustained tuberculosis control in China as well as in the world.

In silico analysis of potential human T Cell antigens from Mycobacterium tuberculosis for the development of subunit vaccines against tuberculosis

In silico analysis was used to predict MHC class I and class II promiscuous epitopes and potential antigens, from 24 novel T cell antigens of Mycobacterium tuberculosis. Majority of the antigens (16/24) had high affinity peptides to both MHC class I and class II alleles and higher population coverage compared to well-proven T cell antigens ESAT-6, CFP-10 and Ag85B. Among these, highest population coverage were calculated for three novel T cell antigens Rv0733 (97.24%), Rv0462 (96.9%) and Rv2251 (96.3%). The prediction results were experimentally tested by in vitro stimulation of these novel T cell antigens with blood drawn from QuantiFERON-TB Gold In-Tube (QFT-IT) positive healthy household contacts of tuberculosis patients and pulmonary TB patients. Significantly higher level interferon-γ (IFN-γ) was observed, with these novel T cell antigens, in healthy household contacts compared to pulmonary TB subjects (p = 0.0001). In silico analysis also resulted in prediction of 36 promiscuous epitopes from the novel 24 T cell antigens. Population coverage for 4 out of the 36 promiscuous epitopes was >90% [67 VVLLWSPRS (Rv1324), 42 VVGVTTNPS (Rv1448c), 178 MRFLLSAKS (Rv0242c) and 842 IRLMALVEY (Rv3800c)]. Our results shows that these novel antigens and promiscuous epitopes identified from our analysis can further be investigated for their usefulness for subunit vaccine development.