Contacts Of Tuberculosis Cases Research Articles

Mycobacterium tuberculosis Infection in School Contacts of Tuberculosis Cases: A Systematic Review and Meta-Analysis.

Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of tuberculosis outcomes from school contacts is not well characterized. We assessed the prevalence of Mycobacterium tuberculosis infection among close school contacts by performing a systematic review. We searched PubMed, Elsevier, China National Knowledge Infrastructure, and Wanfang databases. Studies reporting the number of children who were tested overall and who tested positive were included. Subgroup analyses were performed by study location, index case bacteriological status, type of school, and other relevant factors. In total, 28 studies including 54,707 school contacts screened for M. tuberculosis infection were eligible and included in the analysis. Overall, the prevalence of M. tuberculosis infection determined by the QuantiFERON Gold in-tube test was 33.2% (95% CI, 0.0-73.0%). The prevalences of M. tuberculosis infection based on the tuberculin skin test (TST) using 5 mm, 10 mm, and 15 mm as cutoffs were 27.2% (95% CI, 15.1-39.3%), 24.3% (95% CI, 15.3-33.4%), and 12.7% (95% CI, 6.3-19.0%), respectively. The pooled prevalence of M. tuberculosis infection (using a TST ≥5-mm cutoff) was lower in studies from China (22.8%; 95% CI, 16.8-28.8%) than other regions (36.7%; 95% CI, 18.1-55.2%). The pooled prevalence of M. tuberculosis infection was higher when the index was bacteriologically positive (43.6% [95% CI, 16.5-70.8%] versus 23.8% [95% CI, 16.2-31.4%]). These results suggest that contact investigation and general surveillance in schools from high-burden settings merit consideration as means to improve early case detection in children.

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.

M. tuberculosis Infection Attributable to Exposure in Social Networks of Tuberculosis Cases in an Urban African Community.

The persistence of tuberculosis today and its global disparity send a powerful message that effective tuberculosis control must respond to its regional epidemiology. Active case finding through contact investigation is a standard protocol used for tuberculosis control, but its effectiveness has not been established, especially in endemic areas. To quantify the potential effectiveness of contact investigation in Kampala, Uganda, we used a cross-sectional design to evaluate the social networks of 123 tuberculosis index cases and 124 controls without tuberculosis. Tuberculous infection was present in 515 of 989 tuberculosis case contacts (52.1%) and 396 of 1026 control contacts (38.6%; adjusted prevalence ratio, 1.4; 95% CI, 1.3-1.6). The proportion of infected participants with known exposure within the social network of the tuberculosis case was 35%. The population-attributable fraction was 11.1% for any known exposure, with 7.3% attributable to household exposure and 3.4% attributable to extrahousehold exposure. This low population-attributable fraction indicates that contact tracing in the social networks of index cases will have only a modest effect in reducing tuberculous infection in a community. New approaches to community-level active case finding are needed.

Prevalence of latent tuberculosis infection and incidence of tuberculin conversion among school contacts older than 5 years in the City of Buenos Aires.

Introduction. Tuberculosis continues to be a common problem in settings of socioeconomic vulnerability. Our primary objective was to establish the prevalence of latent infection and tuberculin conversion among school contacts of tuberculosis cases. Population and methods. In a programmatic area in the south of the City of Buenos Aires, the prevalence of latent infection and tuberculin conversion was assessed in 691 children and adolescents using the tuberculin skin test. The association between loss to follow-up by the health care team and the demographic, school, and baseline care characteristics was studied, and the level of adherence when isoniazid chemoprophylaxis was indicated was described. Results. According to established definitions, the prevalence of latent infection was between 3.4% (95% confidence interval [CI]: 2.3-5.2) and 11.6% (95% CI: 9.3-14.4) in the 610 contacts with at least one skin test. The incidence of tuberculin conversion was between 0.3% and 6.8% in the 294 assessed participants. Age older than 18 years, a higher prevalence of unmet basic needs in the school district, attending the afternoon school shift, negative sputum smear results in the index case, and absence of baseline skin test were associated with contact lost to follow-up. Conclusions. The incidence of tuberculin conversion among school contacts was low. Adherence to isoniazid treatment remains limited. Factors associated with loss of contact tracing were identified, which may guide strategies necessary to improve this process.

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).

Isoniazid preventive therapy completion in children under 5 years old who are contacts of tuberculosis cases in Lima, Peru: study protocol for an open-label, cluster-randomized superiority trial

BackgroundChildren < 5 years old in contact with TB cases are at high risk for developing severe and fatal forms of TB. Contact investigation, BCG vaccination, and isoniazid preventive therapy (IPT) are the most effective strategies to prevent TB among children. However, the implementation of IPT faces challenges at several stages of the cascade of care of TB infection among children, particularly those less than 5 years old. In Peru, a large proportion of children do not complete IPT, which highlights the need to design effective interventions that enhance preventive therapy adherence and completion. Although the body of evidence for such interventions has grown, interventions in medium TB incidence settings are lacking. This study aims to test the effectiveness, acceptability, and feasibility of an intervention package to increase information and motivation to complete IPT among children < 5 who have been prescribed IPT.MethodsAn open-label, cluster-randomized superiority trial will be conducted in two districts in South Lima, Peru. Thirty health facilities will be randomized as clusters, 10 to the intervention and 20 to control (standard of care). We aim to recruit 10 children from different households in each cluster. Participants will be caretakers of children aged < 5 years old who initiated IPT. The intervention consists of educational material, and short message services (SMS) reminders and motivators. The primary outcomes will be the proportion of children who picked up > 90% of the 24 weeks of IPT (22 pick-ups) and the proportion of children who picked up the 24 weeks of IPT. The standard of care is a weekly pick-up with monthly check-ups in a health facility. Feasibility and acceptability of the intervention will be assessed through an interview with the caretaker.DiscussionUnfavorable outcomes of TB in young children, high effectiveness of IPT, and low rates of IPT completion highlight the need to enhance adherence and completion of IPT among children < 5 years old. Testing of a context-adapted intervention is needed to improve IPT completion rates and therefore TB prevention in young children.Trial registrationClinicalTrials.gov NCT03881228. Registered on March 19, 2019.

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&lt;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.

Impact of the COVID-19 pandemic on contact tracing of patients with pulmonary tuberculosis.

BackgroundThe COVID-19 pandemic could have negative effects on tuberculosis (TB) control. The objective was to assess the impact of the pandemic in contact tracing, TB and latent tuberculosis infection (LTBI) in contacts of patients with pulmonary TB in Catalonia (Spain).MethodsContact tracing was carried out in cases of pulmonary TB detected during 14 months in the pre-pandemic period (1 January 2019 to 28 February 2020) and 14 months in the pandemic period (1 March 2020 to 30 April 2021). Contacts received the tuberculin skin test and/or interferon gamma release assay and it was determined whether they had TB or LTBI. Variables associated with TB or LTBI in contacts (study period and sociodemographic variables) were analyzed using adjusted odds ratio (aOR) and the 95% confidence intervals (95% CI).ResultsThe pre-pandemic and pandemic periods showed, respectively: 503 and 255 pulmonary TB reported cases (reduction of 50.7%); and 4676 and 1687 contacts studied (reduction of 36.1%). In these periods, the proportion of TB cases among the contacts was 1.9% (84/4307) and 2.2% (30/1381) (P = 0.608); and the proportion of LTBI was 25.3% (1090/4307) and 29.2% (403/1381) (P < 0.001). The pandemic period was associated to higher LTBI proportion (aOR = 1.3; 95% CI 1.1–1.5), taking into account the effect on LTBI of the other variables studied as sex, age, household contact and migrant status.ConclusionsCOVID-19 is affecting TB control due to less exhaustive TB and LTBI case detection. An increase in LTBI was observed during the pandemic period. Efforts should be made to improve detection of TB and LTBI among contacts of TB cases.

A prevalence study in Guadalajara, Mexico, comparing tuberculin skin test and QuantiFERON-TB Gold In-Tube.

Tuberculosis (TB) is a prevalent disease throughout the world. The extent of TB illness in childhood is not clear; recent data shows that 10-20% of the cases are found in children under 15 years old. In 2017, 1 million children developed the disease, of which 9% were co-infected with HIV. A cross-sectional study that analyzed 48 children diagnosed with HIV-infection in Guadalajara, Mexico. The tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFT) were performed and compared to diagnose latent TB infection (LTBI). The average age was 9 years old (± 4), with an age range of 1-16 years; the 6-12-year-old group predominated with 50% of cases. 27 patients (56%) were male; 83% had received the BCG vaccination and 23% had a history of being contacts of TB cases. In the study, 40 patients (83%) were without immunosuppression; seven (15%) with moderate immunosuppression, and only one patient had severe immunodeficiency. Overall, 3 of the 48 children (6.2%) had a positive TST, while 8 out of 48 (16.6%) had a positive QFT. The concordance between the two tests was 89.6% (43/48) with Kappa = 0.5 (95% CI, 0.14-0.85). The QFT test represents an opportunity in the diagnosis of LTBI, particularly in pediatric HIV- patients. This is the first study that compares the two tests (TST and QFT) in children with HIV-infection in Guadalajara, Mexico.

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) &lt; 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.

Excess Risk of Tuberculosis Infection Among Extra-household Contacts of Tuberculosis Cases in an African City.

Although households of tuberculosis (TB) cases represent a setting for intense transmission of Mycobacterium tuberculosis, household exposure accounts for <20% of transmission within a community. The aim of this study was to estimate excess risk of M. tuberculosis infection among household and extra-household contacts of index cases. We performed a cross-sectional study in Kampala, Uganda, to delineate social networks of TB cases and matched controls without TB. We estimated the age-stratified prevalence difference of TB infection between case and control networks, partitioned as household and extra-household contacts. We enrolled 123 index cases, 124 index controls, and 2415 first-degree network contacts. The prevalence of infection was highest among household contacts of cases (61.5%), lowest among household contacts of controls (25.2%), and intermediary among extra-household TB contacts (44.9%) and extra-household control contacts (41.2%). The age-adjusted prevalence difference between extra-household contacts of cases and their controls was 5.4%. The prevalence of infection was similar among the majority of extra-household case contacts and corresponding controls (47%). Most first-degree social network members of TB cases do not have adequate contact with the index case to experience additional risk for infection, but appear instead to acquire infection through unrecognized exposures with infectious cases in the community.

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.

Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil

BackgroundHost genetic polymorphisms may be important in determining susceptibility to Mycobacterium tuberculosis (Mtb) infection, but their role is not fully understood. Detection of microbial DNA and activation of type I interferon (IFN) pathways regulate macrophage responses to Mtb infection. MethodsWe examined whether seven candidate gene SNPs were associated with tuberculin skin test (TST) positivity in close contacts of microbiologically confirmed pulmonary TB patients in Brazil. Independent associations with TST positivity were tested using multivariable logistic regression (using genotypes and clinical variables) and genetic models. ResultsAmong 482 contacts of 145 TB index cases, 296 contacts were TST positive. Multivariable regression analysis adjusted for population admixture, age, family relatedness, sex and clinical variables related to increased TB risk demonstrated that SNPs in PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR]: 3.72; 95%CI=1.15–12.0; p=0.028) and in PYHIN1-IFI16-AIM2 rs1633256 (aOR=24.84; 95%CI=2.26–272.95; p=0.009) were associated with TST positivity in a recessive model. Furthermore, an IRF7 polymorphism (rs11246213) was associated with reduced odds of TST positivity in a dominant model (aOR: 0.50, 95%CI: 0.26-0.93; p=0.029). ConclusionsPolymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort.

Evolution, Trends, and Potential Explanations of the Increase in the Incidence of Tuberculosis: the Case of Uruguay

A descriptive analysis of the trend of tuberculosis incidence in Uruguay between 1995 and 2018. In 2015, World Health Organization (WHO) proposed The END TB Strategy; the Latin American countries that implemented these strategies at the first level of care have had successful outcomes in terms of the reduction in the incidence, morbidity, and mortality of the disease. Uruguay is a striking case in the regional environment regarding tuberculosis epidemiology. The trend of tuberculosis had a turning point in 2006, which defines two clearly different periods. The first period covers the year 1995 to 2006 and shows a significant decrease in the incidence rate and the second period covers the year 2006 to 2018 and shows a significant increase in the incidence rate. The proportion of contacts of tuberculosis cases receiving prophylactic treatment, the percentage of cases lost to follow-up, and the magnitude of the bacillary burden at diagnosis moment are possible factors linked to the changes in the trend of the incidence of tuberculosis. The initiation of a gradual transfer of the responsibilities of the National Program of Tuberculosis in diagnosis, treatment, and prevention to primary care health providers in the National Integrated Health System will hopefully contribute to reverse the epidemiological situation of tuberculosis in the country.

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.