Household Contacts Of Tuberculosis Patients Research Articles

Discovery of a blood-based miRNA signature that can predict onset of active tuberculosis among household contacts of TB patients

BackgroundNon-sputum based predictive biomarkers capable of identifying individuals with high risk of progression to active tuberculosis (TB) are critical for global TB control. MicroRNAs (miRNAs) are significant regulators involved in TB pathogenesis and hence we aimed to identify a miRNA signature capable of predicting progression to TB disease.MethodsWe compared the differential miRNA expression profile of QuantiFERON supernatants of TB Progressors, defined as healthy household contacts (HHCs) of TB patients, who developed active TB disease during a 2-year follow-up period, and Non-progressors defined as HHCs from the same longitudinal cohort who did not develop TB disease during the entire follow-up period, using the nanostring nCounter platform. Receiver Operator Characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of the identified miRNA biomarkers, followed by random forest analysis to determine the best predictive model.ResultsWe identified 30 differentially regulated miRNAs between the two groups. Of these, hsa-miR-585-3p and hsa-miR-92a-3p were up-regulated with a maximum fold change of 1.74 and 1.71 respectively, while hsa-miR-223-3p and hsa-miR-451a were down-regulated by −2.05 and −2.04 fold respectively. Random forest analysis revealed that hsa-miR-181a-5p, hsa-miR-204-5p, hsa-miR-197-3p, hsa-miR-92a-3p, hsa-miR-451a, hsa-miR-24-3p, and hsa-miR-487a-3p exhibited 100% accuracy in identifying Progressors. This panel of 7 miRNAs demonstrated excellent diagnostic performance characteristics with 100% sensitivity and specificity.ConclusionWe propose that the identified miRNA signature has the potential to serve as a very useful tool for early identification of individuals who bear the highest risk of progression to TB, so that they can be targeted for timely intervention.

Elucidating the effect of pro and anti-inflammatory recombinant cytokines TNF-α and TGF-β in tuberculosis

Tuberculosis (TB) is a leading cause of death caused by Mycobacterium tuberculosis (M tb) and about one-third of the world’s population is infected with TB. The household contacts of TB patients are at higher risk towards TB than general population. During the initial stages of infection, pro and anti-inflammatory cytokines are induced by innate immune cells, and the course of infection is influenced by general cytokine environment. These cytokines play an important role in the regulation of host immune responses against M tb. Therefore, it is necessary to understand the cytokines role in the immune mechanism to evaluate the correlation between the disease and the immune responses involved in TB. Our current study has focused on recombinant cytokines to understand their effects on cell proliferation and cytokine levels in culture supernatants. We observed that the mean proliferative responses to recombinant rhTNF-α were high and TNF-α levels were significantly low in APTB patients compared to their HHC and HC with p < 0.0375 and p < 0.0051 respectively. The mean proliferative responses to recombinant rhTGF-β were significantly low in APTB when compared to HHC and HC with p < 0.0376, p < 0.0247 respectively, and TGF-β levels were also significantly low in APTB and HHC compared to HC with p < 0.0468 and p < 0.0001 respectively. The lower cytokine secretions in culture supernatants might be due the autocrine signaling by recombinant cytokines towards the inflammatory response. Further, to validate these recombinant cytokines, a larger sample size could aid in identifying individuals at high risk for TB.

Plasma Immune Biomarkers Predictive of Progression to Active Tuberculosis in Household Contacts of TB Patients.

The progression from Mycobacterium tuberculosis infection to active tuberculosis (TB) disease varies among individuals, and identifying biomarkers to predict progression is crucial for guiding interventions. In this study, we aimed to determine plasma immune biomarker profiles in healthy household contacts of index pulmonary TB (PTB) patients who either progressed to TB or remained as non-progressors. A cohort of household contacts of adults with PTB was enrolled, consisting of 15 contacts who progressed to TB disease and 15 non-progressors. Plasma samples were collected at baseline, 4 months, and 12 months to identify predictive TB progression markers. Our findings revealed that individuals in the progressor group exhibited significantly decreased levels of IFNγ, IL-2, TNFα, IL1α, IL1β, IL-17A, and IL-1Ra at baseline, months 4 and 12. In contrast, the progressor group displayed significantly elevated levels of IFNα, IFNβ, IL-6, IL-12, GM-CSF, IL-10, IL-33, CCL2, CCL11, CXCL8, CXCL10, CX3CL1, VEGF, Granzyme-B and PDL-1 compared to the non-progressor group at baseline, months 4 and 12. ROC analysis identified IFNγ, GM-CSF, IL-1Ra, CCL2 and CXCL10 as the most promising predictive markers, with an AUC of ≥90. Furthermore, combinatorial analysis demonstrated that GM-CSF, CXCL10 and IL-1Ra, when used in combination, exhibited high accuracy in predicting progression to active TB disease. Our study suggests that a specific set of plasma biomarkers GM-CSF, CXCL10 and IL-1Ra, can effectively identify household contacts at significant risk of developing TB disease. These findings have important implications for early intervention and preventive strategies in TB-endemic regions.

History of tuberculosis disease is associated with genetic regulatory variation in Peruvians.

A quarter of humanity is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses to Mtb infection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs). We recruited former household contacts of TB patients who previously progressed to TB (cases, n = 63) or did not progress to TB (controls, n = 63). Transcriptomic profiling of monocyte-derived DCs and macrophages measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified 330 and 257 eQTL genes in DCs and macrophages (False Discovery Rate (FDR) < 0.05), respectively. Four genes in DCs showed interaction between eQTL variants and TB progression status. The top eQTL interaction for a protein-coding gene was with FAH, the gene encoding fumarylacetoacetate hydrolase, which mediates the last step in mammalian tyrosine catabolism. FAH expression was associated with genetic regulatory variation in cases but not controls. Using public transcriptomic and epigenomic data of Mtb-infected monocyte-derived dendritic cells, we found that Mtb infection results in FAH downregulation and DNA methylation changes in the locus. Overall, this study demonstrates effects of genetic variation on gene expression levels that are dependent on history of infectious disease and highlights a candidate pathogenic mechanism through pathogen-response genes. Furthermore, our results point to tyrosine metabolism and related candidate TB progression pathways for further investigation.

Tuberculosis preventive treatment among the household contacts of tuberculosis patients – Coverage and correlates in a block of Murshidabad district, West Bengal: A cross-sectional study

BackgroundIndia started implementing tuberculosis preventive treatment (TPT) among all household contacts of Tuberculosis (TB) cases, as a globally accepted strategy for elimination of TB. ObjectivesWe aimed to assess the extent of TPT coverage and adherence; ascertain the reasons for non-initiation and non-adherence; and to determine the correlates of coverage. MethodsWe conducted a cross-sectional study in a block of Murshidabad district, West Bengal during September–November’2023. A calculated sample of 301 eligible household contacts of ‘index cases’ (microbiologically-confirmed drug-sensitive pulmonary TB) registered during October’22 to March’23 were studied. We interviewed the participants/respondents with pre-designed schedule and prior informed consent. Descriptive and inferential statistics were applied through Statistical Package for Social Sciences (version 20). ResultsOf 301 contacts, 179(59.5%) individually traced/counseled at the household; 238 (79.1%) were screened for TB symptoms. TPT initiation was 74.8% (225/301) with 47.1% within seven days of treatment initiation of index case; TPT not offered by health personnel (59.2%) being major reason for non-initiation. Completion rate with adherence to full course was 69.3% (156/225); perceived lack of need (50.7%) and migration (21.7%) being major reasons for non-adherence. Overall coverage of full course TPT among total eligible contacts was only 51.8% (156/301). On multivariable logistic regression; male gender (aOR = 1.982; 95% CI = 1.004–3.915), contacts with individual tracing/counseling (aOR = 13.507; 95% CI = 6.781–26.906) and who had symptoms screening (aOR = 5.694; 95% CI = 2.223–14.587) predicted significantly higher TPT coverage. ConclusionCascade of care indicators for TPT remains suboptimal in the area and indicates need for further strengthening of programmatic aspects of its implementation.

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 coronavirus disease 2019 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 30.0% for each 1-point score increase in preventive behavior (odds ratio, 0.70; 95% confidence interval, 0.61 to 0.79). 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.

Knowledge and Practices of Airborne Infection Control at the Household Level among Pulmonary Tuberculosis Patients Attending a Tertiary Care Teaching Hospital in Central Karnataka, India

Abstract Background: Airborne transmission of tuberculosis (TB) is a major route of spread. Household contacts of TB patients are at high risk of infection. However, there is limited evidence on airborne infection control knowledge and practices among TB patients in India. This study was done to assess the knowledge and practices related to airborne infection control among pulmonary TB (PTB) patients at the household level and determine associated factors. Subjects and Methods: A cross-sectional study was conducted among 157 smear-positive PTB patients at a tertiary care hospital in Karnataka, India, using a pretested questionnaire. Knowledge and self-reported practices regarding airborne precautions were assessed. Bivariate analysis was done to determine associated factors. P &lt;0.005 was considered significant. Results: Major gaps were found in knowledge about ventilation (50.3%), avoiding visitors (39.5%), and sputum disposal (33.8%). Suboptimal practices were reported for using tissues (19%), handwashing (25%), ventilation (66%), sputum handling (54%), and waste disposal (30%). Good knowledge was associated with younger age, higher education, Hindu religion, family history of TB, intensive phase treatment, and presence of symptoms (P &lt; 0.05). Participants with good knowledge had significantly better preventive practices (P &lt; 0.00001). Conclusion: Tailored education on airborne precautions focusing on identified knowledge gaps and risky practices can help improve the adoption of infection control measures among TB patients at the household level. A multifaceted approach is required to translate improved awareness into optimal preventive behaviors.

IJCM_285A: Tuberculosis Preventive Treatment among the Household Contacts of Tuberculosis Patients – Coverage and Correlates in a Block of Murshidabad District, West Bengal: A Cross-sectional Study

Background: Tuberculosis preventive treatment (TPT) among close contacts of Tuberculosis (TB) cases is a globally accepted strategy. India targeted elimination of TB by 2025 and started implementing TPT among all household contacts. This intervention needs evaluation in different areas and population groups for effective outcome. Objectives: We aimed to assess the extent of TPT coverage and adherence; ascertain the reasons for non-initiation and non-adherence; and to determine the socio-demographic and programmatic correlates of coverage. Methodology: We conducted a descriptive cross-sectional study during September-November 2023 in a block of Murshidabad district, West Bengal. A sample of 301 eligible household contacts (HHC) of ‘index cases’ (microbiologically-confirmed drug-sensitive pulmonary TB) registered in TB unit of the block during October’22 to March’23 were the study subjects. For child contacts (&lt;12 years), mothers were considered respondents. Participants/respondents were interviewed with a pre-designed schedule with prior informed consent. Descriptive and inferential statistics were applied for analysis through Statistical Package for Social Sciences (version 20). Results: Of 301 contacts, 179 (59.5%) individually traced/counseled at the household; 238 (79.1%) were screened for TB symptoms; 28(11.3%) had sputum examination. TPT initiation rate was 74.8% (225/301) with 47.1% within seven days of diagnosis of index case; not offered by health care providers (59.2%) being major reason for non-initiation. Completion rate with adherence to full course was 69.3% (156/225); perceived lack of need (50.7%), migration (21.7%) being major reasons for non-adherence. Overall coverage of full course TPT among total eligible contacts was only 51.8% (156/301). On multivariable logistic regression; male gender (AOR=1.982; 95% CI=1.004-3.915), HHC with individual tracing/counseling (AOR=13.507; 95% CI= 6.781-26.906) and who had symptoms screening (AOR=5.694; 95% CI=2.223-14.587) predicted significantly higher TPT coverage. Conclusion: Cascade of care indicators for TPT remains suboptimal in the area and highlights the need for further strengthening of programmatic aspects of its implementation.

Knowledge, attitude, and practice toward tuberculosis prevention and management among household contacts in Suzhou Hospital, Jiangsu province, China.

China is among the 10 high-burden tuberculosis (TB) countries in the world; thus, investigation and management of household contacts is an essential part of TB prevention strategy. To explore the knowledge, attitude, and practice (KAP) toward TB prevention and management among household contacts of TB patients. This cross-sectional study enrolled household contacts in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine between September 2022 and January 2023; KAP and demographic characteristics were assessed with the self-designed questionnaire and analyzed by multivariate logistic regression. A total of 503 participants were included; of them, 280 (55.78%) were female, and 303, (60.36%) aged ≥45 years. The KAP scores were 6.24 ± 2.20 (possible range: 0-12), 18.69 ± 2.80 (possible range: 0-36), and 20.37 ± 5.15 (possible range: 0-36), respectively. Suburban (OR = 0.18, 95% CI: 0.04-0.79, p = 0.023) and rural (OR = 0.12, 95% CI: 0.03-0.57, p = 0.008) were independently associated with knowledge. Positive attitude (OR = 7.03, 95% CI: 2.92-16.96, p < 0.001), education (high school or technical secondary school, OR = 4.91, 95% CI: 1.63-14.73, p = 0.005; college and above, OR = 14.94, 95% CI: 3.51-63.58, p < 0.001), and shorter disease duration (3-6 months, OR = 0.40, 95% CI: 0.18-0.90, p = 0.026) were independently associated with better practice scores. Household contacts of TB patients demonstrated insufficient knowledge, unfavorable attitude, and suboptimal practice toward TB prevention and management. Tailored interventions are needed to ensure information accessibility, especially for individuals living in suburban and rural areas.

Tuberculosis Preventive Behaviors and their Determining Factors among Household Contacts of Tuberculosis Patients in Thailand: A Cross-sectional Study

Background Tuberculosis (TB) places a substantial burden on global public health, particularly in developing countries—including Thailand. Household contacts (HHCs) of individuals infected with TB are considered high risk due to their elevated risk of catching and transmitting the disease. Objectives This study explores TB preventive behaviors and their determining factors among HHCs of TB patients. Methods A cross-sectional study of 245 HHCs who cared for TB patients was conducted in 2022. A questionnaire was used to collect data, which were analyzed using descriptive statistics and stepwise multiple regression analysis. Results The overall mean score for all the TB preventive behaviors combined was high (3.84 ± 0.692). On examining the three domains of TB preventive behaviors, the mean score for healthy self-care behaviors was lower (3.45 ± 0.752) than the mean score for behaviors performed to contain and prevent the spread of TB infection from TB patients (4.09 ± 0.860), as well as that for environmental management behaviors (3.99 ± 0.910). TB preventive behaviors were determined to a statistically significant degree by the response efficacy of TB prevention (b = 0.396, P-value &lt; 0.001), perceived self-efficacy at TB prevention (b = 0.260, P-value = 0.01), and gender (b = −0.146, P-value = 0.047). Conclusion Overall, TB preventive behaviors among HHCs are at a commendable level in Thailand. However, healthcare institutions and relevant agencies need to actively promote healthier self-care behaviors within these HHCs. This advocacy should place a strong emphasis on enhancing conviction in the benefits of TB preventive behaviors and confidence in performing these behaviors, especially among male HHCs.

Nutritional Supplementation to Prevent Infection in Household Contacts of Tuberculosis Patients

Nutritional Supplementation to Prevent Infection in Household Contacts of Tuberculosis Patients

High Isoniazid Preventive Therapy Completion Rate among Household Contacts of Tuberculosis Patients in Duhok Province

High Isoniazid Preventive Therapy Completion Rate among Household Contacts of Tuberculosis Patients in Duhok Province

QuantiFERON Supernatant-Based Host Biomarkers Predicting Progression to Active Tuberculosis Disease Among Household Contacts of Tuberculosis Patients.

The positive predictive value of tuberculin skin test and current generation interferon gamma release assays are very low leading to high numbers needed to treat. Therefore, it is critical to identify new biomarkers with high predictive accuracy to identify individuals bearing high risk of progression to active tuberculosis (TB). We used stored QuantiFERON supernatants from 14 household contacts of index TB patients who developed incident active TB during a 2-year follow-up and 20 age and sex-matched non-progressors. The supernatants were tested for an expanded panel of 45 cytokines, chemokines, and growth factors using the Luminex Multiplex Array kit. We found significant differences in the levels of TB-antigen induced production of several analytes between progressors and non-progressors. Dominance analysis identified 15 key predictive biomarkers based on relative percentage importance. Principal component analysis revealed that these biomarkers could robustly distinguish between the 2 groups. Receiver operating characteristic analysis identified interferon-γ inducible protein (IP)-10, chemokine ligand (CCL)19, interferon (IFN)-γ, interleukin (IL)-1ra, CCL3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as the most promising predictive markers, with area under the curve (AUC) ≥90. IP-10/CCL19 ratio exhibited maximum sensitivity and specificity (100%) for predicting progression. Through Classification and Regression Tree analysis, a cutoff of 0.24 for IP-10/CCL19 ratio was found to be ideal for predicting short-term risk of progression to TB disease with a positive predictive value of 100 (95% confidence interval [CI] 85.8-100). The biomarkers identified in this study will pave way for the development of a more accurate test that can identify individuals at high risk for immediate progression to TB disease for targeted intervention.

Tuberculin test versus interferon gamma release assay in pregnant women with household contacts of tuberculosis patients.

Pregnant women who live in tuberculosis (TB)-affected households are more likely to develop latent TB infection (LTBI), which often escapes treatment. This study aims to determine if Interferon-gamma release (IGRA) is reliable in screening for LTBI in pregnant women, compare to the tuberculin skin test (TST). It was a cross-sectional study that involved 60 pregnant women with TB contact history as a proxy for LTBI and 30 pregnant women without contact history. Latent TB was detected using the TST 5 tuberculin units and IGRA using the QuantiFERON Gold Plus TB Test kit (QFT-Plus). The sensitivity and specificity of the two diagnostic methods and the agreement between them were estimated using SPSS version 20.0. The sensitivity 95% (95% confidence interval [CI]: 86.08%-98.96%) and specificity 26.7% (95% CI: 12.28%-45.89%) of TST were compared to that of the IGRA with 60% (95% CI: 46.54%-72.44%) and 73.3% (95% CI: 54.11%-87.72%) sensitivity and specificity, respectively in detecting LTBI in pregnancy. Although there was a significant difference (P < 0.05) between TST and IGRA, the agreement was fair (kappa 0.39; 95% CI: 0.24-0.45). TST assay is more sensitive than IGRA; however, the specificity of IGRA was superior to the TST method. In this study, a fair agreement of TST and IGRA was observed for detecting latent TB infection in pregnant women with household contact with TB patients.

Linking nationwide health and social registry data to informthe policy for Tuberculosis contact tracing in Brazil.

ObjectivesMitigating the socioeconomic determinants of Tuberculosis (TB) and systematic screening of contacts and high-risk groups are targets of The World Health Organization (WHO) End TB Strategy by 2035. Our aim was to link socioeconomic information to TB datasets to inform policy makers in Brazil and contribute to addressing current challenges.&#x0D; ApproachFollowing a signed technical cooperation agreement with the Ministry of Health (MoH), we linked nationwide data on 1.405.682 registries of TB diagnosed between 2004 and 2019 in Brazil to 131.697.800 demographic and socioeconomic registries from the 100 Million Brazilian Cohort (2001-2018) previously linked to nationwide mortality data. We established close links with TB managers to understand the database, clean and deduplicate registries and to analyse the data. We took advantage of the data structure, to set up a cohort of household contacts of TB patients and produce estimates of TB incidence by subgroups of demographic and socioeconomic characteristics.&#x0D; ResultsThe interaction of the MoH was effective and facilitated by a robust TB Programme in the country. 567.999 (40,41%) TB cases were linked to the 100 Million Brazilian Cohort with high specificity (93.6%) and sensitivity (94.6%). Using family identifiers, we established the first TB case within a family unit (i.e., primary case) and followed their household contacts up to 15 years. We found the TB incidence among household contacts to be 427.8/100.000 person-years (95%CI 419.1-436.8). In the first year following the identification of the primary case, there was higher cumulative incidence among household contacts under 5 years of age, which was followed by a plateau of cases in this age group. Cummulative incidence in the other age groups presented a constant increase over time.&#x0D; ConclusionThe close collaboration with the MoH, the development of an effective linkage algorithm and the availability of large socioeconomic data allowed for a unique analysis of the high incidence of TB among household contacts. Findings reinforce need for constant dialogue among stakeholders to strengthen case detection by primary health care.

Scaling up investigation and treatment of household contacts of tuberculosis patients in Brazil: a cost-effectiveness and budget impact analysis

In Brazil, investigation and treatment of tuberculosis infection (TBI) in households contacts (HHC) of TB patients is not a priority. We estimated the cost-effectiveness and budget-impact of scaling-up an enhanced HHC management in Brazil. We conceptualized a cascade-of-care that captures how HHC of tuberculosis patients are investigated in Brazil (status quo) and two enhanced strategies for management of HHC focusing on: (1) only tuberculosis disease (TBD) detection and, (2) TBD and TBI detection and treatment. Effectiveness was the number of HHC diagnosed with TBD and completing TBI treatment. Proportions in the cascades-of-care were derived from a meta-analysis. Health-system costs (2019 US$) were based on literature and official data from Brazil. The impact of enhanced strategies was extrapolated using reported data from 2019. With the status quo, 0 (95% uncertainty interval: 0-1) HHC are diagnosed with TBD and 2 (0-16) complete TBI treatment. With strategy(1), an additional 15 (3-45) HHC would be diagnosed with TBD at a cost of US$346 each. With strategy(2), 81 (19-226) additional HHC would complete TBI treatment at a cost of US$84 each. A combined strategy, implemented nationally to enhance TBD detection and TBI treatment would result in an additional 9,711 (845-28,693) TBD being detected, and 51,277 (12,028-143,495) more HHC completing TBI treatment each year, utilizing 10.9% and 11.6% of the annual national tuberculosis program budget, respectively. Enhanced detection and treatment of TBD and TBI among HHC in Brazil can be achieved at a national level using current tools at reasonable cost. None.

Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk.

In the current study, we followed 839 household contacts (HHCs) of tuberculosis (TB) patients for 2 years and identified the factors that enhanced the development of TB. Fourteen of the 17 HHCs who progressed to TB were in the 15- to 30-year-old age group. At baseline (the “0“ time point, when all the individuals were healthy), the concentration of the thyroid hormone thyroxine (T4) was lower, and there were increased numbers of Tregs in PBMCs of TB progressors. At baseline, PBMCs from TB progressors stimulated with early secretory antigenic target 6 (ESAT-6) and 10 kDa culture filtrate antigen (CFP-10) produced less IL-1α. Thyroid hormones inhibited Mycobacterium tuberculosis (Mtb) growth in macrophages in an IL-1α–dependent manner. Mtb-infected Thra1PV/+ (mutant thyroid hormone receptor) mice had increased mortality and reduced IL-1α production. Our findings suggest that young HHCs who exhibit decreased production of thyroid hormones are at high risk of developing active TB disease.

Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in Zambia and South Africa

BackgroundA more stringent QuantiFERON-TB Gold In-Tube (QFT) conversion (from negative to positive) definition has been proposed to allow more definite detection of recent tuberculosis (TB) infection. We explored alternative conversion definitions to assist the interpretation of serial QFT results and estimate incidence of TB infection in a large cohort study.MethodsWe used QFT serial results from TB household contacts aged ≥15 years, collected at baseline and during two follow-up visits (2006–2011) as part of a cohort study in 24 communities in Zambia and South Africa (SA). Conversion rates using the manufacturers’ definition (interferon-gamma (IFN-g) < 0.35 to ≥0.35, ‘def1’) were compared with stricter definitions (IFN-g < 0.2 to ≥0.7 IU/ml, ‘def2’; IFN-g < 0.2 to ≥1.05 IU/ml, ‘def3’; IFN-g < 0.2 to ≥1.4 IU/ml, ‘def4’). Poisson regression was used for analysis.ResultsOne thousand three hundred sixty-five individuals in Zambia and 822 in SA had QFT results available. Among HIV-negative individuals, the QFT conversion rate was 27.4 per 100 person-years (CI:22.9–32.6) using def1, 19.0 using def2 (CI:15.2–23.7), 14.7 using def3 (CI:11.5–18.8), and 12.0 using def4 (CI:9.2–15.7). Relative differences across def1-def4 were similar in Zambia and SA. Using def1, conversion was less likely if HIV positive not on antiretroviral treatment compared to HIV negative (aRR = 0.7, 95%CI = 0.4–0.9), in analysis including both countries. The same direction of associations were found using def 2–4.ConclusionHigh conversion rates were found even with the strictest definition, indicating high incidence of TB infection among household contacts of TB patients in these communities. The trade-off between sensitivity and specificity using different thresholds of QFT conversion remains unknown due to the absence of a reference standard. However, we identified boundaries within which an appropriate definition might fall, and our strictest definition plausibly has high specificity.

The potential impact of preventive therapy against tuberculosis in the WHO South-East Asian Region: a modelling approach

BackgroundThe prevention of tuberculosis (TB) is key for accelerating current, slow declines in TB burden. The 2018 World Health Organization (WHO) guidelines on eligibility for preventive therapy to treat latent TB infection (LTBI) include people living with human immunodeficiency virus (PLHIV), household contacts of TB patients including children, and those with clinical conditions including silicosis, dialysis, transplantation, etc. and other country-specific groups. We aimed to estimate the potential impact of full implementation of these guidelines in the WHO South-East Asian (SEA) Region, which bears the largest burden of TB and LTBI amongst the WHO regions.MethodsWe developed mathematical models of TB transmission dynamics, calibrated individually to each of the 11 countries in the region. We modelled preventive therapy in the absence of other TB interventions. As an alternative comparator, reflecting ongoing developments in TB control in the region, we also simulated improvements in the treatment cascade for active TB, including private sector engagement and intensified case-finding. Relative to both scenarios, for each country in the region, we projected TB cases and deaths averted between 2020 and 2030, by full uptake of preventive therapy, defined as comprehensive coverage amongst eligible populations as per WHO guidelines, and assuming outcomes consistent with clinical trials. We also performed sensitivity analysis to illustrate impact under less-than-optimal conditions.ResultsAt the regional level, full uptake of preventive therapy amongst identified risk groups would reduce annual incidence rates in 2030 by 8.30% (95% CrI 6.48–10.83) relative to 2015, in the absence of any additional interventions. If implemented against a backdrop of improved TB treatment cascades, preventive therapy would achieve an incremental 6.93 percentage points (95% CrI 5.81–8.51) of reduction in annual incidence rates, compared to 2015. At the regional level, the numbers of individuals with latent TB infection that need to be treated to avert 1 TB case is 64 (95% CrI 55–74). Sensitivity analysis illustrates that results for impact are roughly proportional to ‘effective coverage’ (the product of actual coverage and effectiveness of the regimen).ConclusionsFull implementation of WHO guidelines is important for ending TB in the SEA Region. Although future strategies will need to be expanded to the population level, to achieve large declines in TB incidence, the uptake of current tools can offer a valuable step in this direction.

Combined Tuberculosis and Diabetes Mellitus Screening and Assessment of Glycaemic Control among Household Contacts of Tuberculosis Patients in Yangon, Myanmar.

Background: This study aimed to identify the prevalence of diabetes mellitus (DM) and tuberculosis (TB) among household contacts of index TB patients in Yangon, Myanmar. Method: Household contacts were approached at their home. Chest X-ray and capillary blood glucose tests were offered based on World Health Organization and American Diabetes Association guidelines. Crude prevalence and odds ratios of DM and TB among household contacts of TB patients with and without DM were calculated. Results: The overall prevalence of DM and TB among household contacts were (14.0%, 95% CI: 10.6–18.4) and (5%, 95% CI: 3.2–7.6), respectively. More than 25% of DM cases and almost 95% of TB cases among household contacts were newly diagnosed. Almost 64% of known DM cases among household contacts had poor glycaemic control. The risk of getting DM among household contacts of TB patients with DM was significantly higher (OR—2.13, 95% CI: 1.10–4.12) than those of TB patients without DM. There was no difference in prevalence of TB among household contacts of TB patients with and without DM. Conclusion: Significant proportions of the undetected and uncontrolled DM among household contacts of index TB patients indicate a strong need for DM screening and intervention in this TB–DM dual high-risk population.