Contacts Of Pulmonary Tuberculosis Patients Research Articles

Economic evaluation of diagnosis and treatment for latent tuberculosis infection among contacts of pulmonary tuberculosis patients in Thailand

Currently, interferon-gamma release assay (IGRA) is costly and not included as latent tuberculosis infection (LTBI) screening test strategy in Thailand’s Universal Coverage Scheme (UCS) benefit package. The objective of this study was to assess the cost-utility of LTBI screening strategies among tuberculosis (TB) contacts in Thailand. A hybrid decision tree and Markov model was developed to compare the lifetime costs and health outcomes of tuberculin skin test (TST) and IGRA, in comparison to no screening, based on a societal perspective. Health outcomes were the total number of TB cases averted and quality-adjusted life years (QALYs), with results presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to explore uncertainties in all parameters. The ICER of TST compared with no screening was 27,645 baht per QALY gained, while that of IGRA compared to TST was 851,030 baht per QALY gained. In a cohort of 1000 TB contacts, both TST and IGRA strategies could avert 282 and 283 TB cases, respectively. At the Thai societal willingness-to-pay threshold of 160,000 baht per QALY gained, TST was deemed cost-effective, whereas IGRA would not be cost-effective, unless the cost of IGRA was reduced to 1,434 baht per test.

Adherence to preventive treatment for latent tuberculosis infection in close contacts of pulmonary tuberculosis patients: A cluster-randomized controlled trial in China

ObjectivesThis study examined adherence rates to tuberculosis preventive treatment (TPT) among close contacts of individuals with pulmonary tuberculosis (PTB) and identified factors associated with TPT adherence in China. MethodsA multicenter, cluster-randomized, open-label control trial was carried out across three sites involving 34 counties in China. Close contacts of bacteriologically confirmed rifampin and isoniazid-susceptible PTB cases were identified and screened for latent tuberculosis infection (LTBI). Eligible participants were randomly assigned to either the 3H2P2 group, which consisted of a 3-month, twice-weekly regimen of rifapentine and isoniazid, or the 6H group, which entailed a 6-month daily regimen of isoniazid. To assess the factors influencing adherence, a two-level logistic regression model was utilized. ResultsOut of the 2434 close contacts who initiated TPT, 2121 (87.1%) completed the regimen. Of the 313 individuals who did not complete TPT, 60.1% refused to continue, and 27.8% discontinued due to adverse effects. The two-level logistic regression model revealed several factors associated with enhanced TPT adherence: enrollment in the 3H2P2 group (odds ratio [OR] = 2.09), management by a TB dispensary responsible for TPT (OR = 2.55), supervision by healthcare workers (OR = 6.40), and clinician incentives (OR = 2.49). Conversely, the occurrence of any adverse effects (OR = 0.08) was identified as a risk factor for nonadherence. ConclusionAdministering TPT to individuals with LTBI is feasible among close contacts. Adherence to TPT can be enhanced through shorter, safer treatment regimens and supportive interventions, such as directly supervised therapy for TPT recipients and incentives for healthcare providers managing TPT.

Nitric oxide brings innate immune resistance to M. tuberculosis infection among high-risk household contacts of pulmonary tuberculosis patients

Nitric oxide brings innate immune resistance to M. tuberculosis infection among high-risk household contacts of pulmonary tuberculosis patients

Latent tuberculosis infection care cascade among the household contacts of pulmonary tuberculosis patients – Findings from an urban feasibility study

IntroductionLatent Tuberculosis infection (LTBI) care cascade involves identification of high-risk individuals, testing, identification of LTBI, initiation of Tuberculosis Preventive therapy (TPT) and documentation of outcomes. There is a dearth of such evidence in Indian setting which needs to be further explored. Hence, this feasibility study with public private engagement was conducted with the primary objective of estimating the prevalence of LTBI among household contacts (HHCs) of pulmonary tuberculosis patients using Interferon gamma release assay (IGRA). Secondary objective was to determine the treatment outcomes among the patients of LTBI initiated on TPT. MethodsThis longitudinal community-based study was conducted in wards 47–51 at urban field practice area of our Tertiary Teaching Institute at Bhopal, Madhya Pradesh. The household contacts of pulmonary tuberculosis patients diagnosed from January–June 2022 and those who satisfied the study criteria were recruited. Those who gave consent for IGRA testing and TPT initiation were followed up for a period of 6 months to assess the treatment outcomes. Data was analyzed using R software. ResultsOf the 64 HHCs screened, 29 were the contacts of microbiologically positive and 35 were the contacts of clinically diagnosed index Tb patients including 4 under five children. Prevalence of LTBI using IGRA was 74.5%. The Contact Investigation Coverage in the urban setting was 77.1% with TPT completion of 72.4% and TPT Coverage of 55.7%. The median time for screening the HHCs since the diagnosis of index case was 14 days while screening to diagnosis was 2.5 days and that of TPT initiation from diagnosis was 22 days. ConclusionMore than half of those who were tested using IGRA were positive for LTBI. Th public private coordination helped in narrowing the time interval from diagnosis of index tb case to contact tracing and improving the TPT adherence among the HHCs. However, intensive efforts are required to narrow the screening gap of HHCs and TPT initiation. Also, reasons for loss to follow up and missed doses needs to be qualitatively explored.

Transcriptional profiling of human peripheral blood mononuclear cells in household contacts of pulmonary tuberculosis patients provides insights into mechanisms of Mycobacterium tuberculosis control and elimination

ABSTRACT Household contacts (HHCs) of patients with active tuberculosis (ATB) are at higher risk of Mycobacterium tuberculosis (M. tuberculosis) infection. However, the immune factors responsible for different defense responses in HHCs are unknown. Hence, we aimed to evaluate transcriptome signatures in human peripheral blood mononuclear cells (PBMCs) of HHCs to aid risk stratification. We recruited 112 HHCs of ATB patients and followed them for 6 years. Among the HHCs, only 2 developed ATB, while the remaining HHCs were classified into three groups: (1) HHC-1 group (n = 23): HHCs with consistently positive T-SPOT.TB test, negative chest radiograph, and no clinical symptoms or evidence of ATB during the 6-year follow-up period; (2) HHC-2 group (n = 15): HHCs with an initial positive T-SPOT result that later became negative without evidence of ATB; (3) HHC-3 group (n = 14): HHCs with a consistently negative T-SPOT.TB test and no clinical or radiological evidence of ATB. HHC-2 and HHC-3 were combined as HHC-23 group for analysis. RNA sequencing (RNA-seq) in PBMCs, with and without purified protein derivative (PPD) stimulation, identified significant differences in gene signatures between HHC-1 and HHC-23. Gene ontology analysis revealed functions related to bacterial pathogens, leukocyte chemotaxis, and inflammatory and cytokine responses. Modules associated with clinical features in the HHC-23 group were linked to the IL-17 signaling pathway, ferroptosis, complement and coagulation cascades, and the TNF signaling pathway. Validation using real-time PCR confirmed key genes like ATG-7, CXCL-3, and TNFRSF1B associated with infection outcomes in HHCs. Our research enhances understanding of disease mechanisms in HHCs. HHCs with persistent latent tuberculosis infection (HHC-1) showed significantly different gene expression compared to HHCs with no M. tuberculosis infection (HHC-23). These findings can help identify HHCs at risk of developing ATB and guide targeted public health interventions.

Test and Treat Model for Tuberculosis Preventive Treatment among Household Contacts of Pulmonary Tuberculosis Patients in Selected Districts of Maharashtra: A Mixed-Methods Study on Care Cascade, Timeliness, and Early Implementation Challenges.

Tuberculosis preventive treatment (TPT) is an important intervention in preventing infection and reducing TB incidence among household contacts (HHCs). A mixed-methods study was conducted to assess the "Test and Treat" model of TPT care cascade among HHCs aged ≥5 years of pulmonary tuberculosis (PTB) patients (bacteriologically/clinically confirmed) being provided TPT care under Project Axshya Plus implemented in Maharashtra (India). A quantitative phase cohort study based on record review and qualitative interviews to understand the challenges and solutions in the TPT care cascade were used. Of the total 4181 index patients, 14,172 HHCs were screened, of whom 36 (0.3%) HHCs were diagnosed with tuberculosis. Among 14,133 eligible HHCs, 10,777 (76.3%) underwent an IGRA test. Of them, 2468 (22.9%) tested positive for IGRA and were suggested for chest X-ray. Of the eligible 2353 HHCs, 2159 (91.7%) were started on TPT, of whom 1958 (90.6%) completed the treatment. The median time between treatment initiation of index PTB patient and (a) HHC screening was 31 days; (b) TPT initiation was 64 days. The challenges in and suggested solutions for improving the TPT care cascade linked to subthemes were tuberculosis infection testing, chest X-ray, human resources, awareness and engagement, accessibility to healthcare facilities, TPT drugs, follow-up, and assessment. A systematic monitoring and time-based evaluation of TPT cascade care delivery followed by prompt corrective actions/interventions could be a crucial strategy for its effective implementation and for the prevention of tuberculosis.

Mycobacterium tuberculosis -induced monocyte transcriptional responses associated with resistance to tuberculin skin test/interferon-γ release assay conversion in people with HIV.

To determine whether Mycobacterium tuberculosis (Mtb)-induced monocyte transcriptional responses differ in people with HIV (PWH) who do (RSTR) or do not (LTBI) resist tuberculin skin test/interferon-γ (IFN-γ) release assay (TST/IGRA) conversion after exposure. We compared ex-vivo Mtb-induced monocyte transcriptional responses in a Ugandan tuberculosis (TB) household contact study of RSTR and LTBI individuals among PWH. Monocytes were isolated from peripheral blood mononuclear cells from 19 household contacts of pulmonary TB patients, and their transcriptional profiles were measured with RNA-Seq after a 6 h infection with Mtb (H37Rv) or media. Differentially expressed genes (DEGs) were identified by a linear mixed effects model and pathways by gene set enrichment analysis that compared RSTR and LTBI phenotypes with and without Mtb stimulation. Among PWH, we identified 8341 DEGs that were dependent on Mtb stimulation [false discovery rate (FDR) <0.01]. Of these, 350 were not significant (FDR >0.2) in individuals without HIV. Additionally, we found 26 genes that were differentially expressed between RSTR and LTBI monocytes in PWH, including 20 which were Mtb-dependent (FDR <0.2). In unstimulated monocytes, several gene sets [TGF-β signaling, TNF-α signaling via NF-κB, NOTCH signaling, coagulation, and epithelial mesenchymal transition (EMT)] were enriched in RSTR relative to LTBI monocytes (FDR <0.1). These patterns were not observed in individuals without HIV. RSTR monocytes in PWH show different gene expressions in response to Mtb infection when compared with those with LTBI and RSTR without HIV. These differential expression patterns are enriched in inflammatory pathways.

Contact Tracing and Tuberculosis Preventive Therapy for Household Child Contacts of Pulmonary Tuberculosis Patients in the Kyrgyz Republic: How Well Are We Doing?

Early identification, screening and investigation for tuberculosis (TB), and provision of TB preventive therapy (TPT), reduces risk of TB among child household contacts of pulmonary TB patients (index patients). A cohort study was conducted to describe the care cascade and timeliness of contact tracing and TPT initiation among child household contacts (aged < 15 years) of index patients initiated on TB treatment in Bishkek, the Kyrgyz Republic during October 2021-September 2022. In the register, information on the number of child household contacts was available for 153 (18%) of 873 index patients. Of 297 child household contacts identified, data were available for 285, of whom 261 (92%) were screened for TB. More than 50% were screened after 1 month of the index patient initiating TB treatment. TB was diagnosed in 23/285 (9%, 95% CI: 6-13%) children. Of 238 TB-free children, 130 (55%) were eligible for TPT. Of the latter, 64 (49%) were initiated on TPT, of whom 52 (81%) completed TPT. While TPT completion was excellent, there was deficiency in contact identification, timely screening and TPT initiation. Thus, healthcare providers should diligently request and record details of child household contacts, adhere to contact tracing timelines and counsel caregivers regarding TPT.

Protective Role of Vitamin D Against Development of Active Tuberculosis in Close Household Contacts of Pulmonary Tuberculosis Patients: A Prospective Cohort Study.

Vitamin-D is known to promote innate immune responses by acting as a cofactor of VDR for induction of antimicrobial peptides like cathelicidin. Close household contacts of pulmonary tuberculosis patients are at high risk of active infection, Therefore, possible role of vitamin-D in TB prevention through cathelicidin production was studied in high-risk household contacts (HHCs) of pulmonary tuberculosis (PTB) patients. 20 HHCs of PTB patients were recruited and followed up for one year. Levels of vitamin-D (25(OH)D) and its associated molecules were evaluated at 3-months intervals for one year or until the development of active TB. 25(OH)D was measured using chemiluminescence method. Serum VDR and cathelicidin levels were measured by ELISA and VDR mRNA expression by qPCR. Throughout the study period mean range of serum 25(OH)D levels was 20.51 ± 5.12 ng/ml. VDR and cathelicidin levels however showed significant decline after six months suggesting decrease in bacterial exposure. None of the HHCs developed active infection even with high exposure to 2 + to 3 + AFB positive index cases. Mantoux positive household contacts had high levels of VDR and cathelicidin, suggestive of an early or latent phase of infection, did not develop active TB plausibly due to maintenance of adequate serum levels of vitamin-D. Optimal levels of 25(OH)D and its associated molecules during early stages of infection may serve as protective factor against development of active TB. Cohort of HHCs with severely deficient vitamin-D levels (10 ng/ml) could be followed up for a better risk assessment.

Strategies to detect and manage latent tuberculosis infection among household contacts of pulmonary TB patients in high TB burden countries - a systematic review and meta-analysis.

To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries. PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised. From 3694unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%-100%; 46 studies). Random-effects meta-analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%-49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%-97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%-74%; 108,679 TPT-initiated contacts, 28 studies). Heterogeneity was significant (I2 ≥ 95%-100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%-59%); TPT initiation 86% (60%-100%); TPT completion 68% (44%-82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade. The proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient.

The intention to receive tuberculosis preventive therapy in adult household contacts of pulmonary TB patients in Delhi, India.

The integration of newer tuberculosis preventive therapy regimens, which have shorter treatment duration, simpler dosing requirements, and improved safety profile, is being considered within India's national tuberculosis elimination program. However, a potential operational challenge in the successful rollout of the expanded TPT plan is the extent of its acceptability in adult household contacts of pulmonary tuberculosis patients due to possibility of lower risk perception and suboptimal perceived benefit. This study was conducted to determine the intention to accept Tuberculosis Preventive Therapy among adult household contacts of pulmonary tuberculosis patients in Delhi, India. This cross-sectional study was conducted from June-November 2020 in Delhi, India. Data were collected through face to-face interviews by trained field investigations from the high-risk adult household contacts of PTB patients. A total of 536 household contacts including 237 (44.2%) men and 299 (55.8%) women were recruited with median (IQR) age 40 (22-52) years. Risk factors for incident tuberculosis observed in the HHCs were undernourishment (32.3%), overweight (47.8%), and diabetes comorbidity (10.6%). Most of the participants had not heard of latent TB infection (97.3%) The intention to accept tuberculosis preventive therapy was reported by 394 (73.5%) participants with an absence of symptoms (33.1%), feeling completely healthy (42.9%), and drug adverse effects (27.5%) (n=142) being primary drivers of non-intention. Nearly three in four HHCs without TB disease expressed willingness to accept TPT if prescribed with caveat for the social desirability bias.

The Kynurenine/Tryptophan Ratio Is a Sensitive Biomarker for the Diagnosis of Pediatric Tuberculosis Among Indian Children.

ObjectivesPediatric tuberculosis (TB) remains difficult to diagnose. The plasma kynurenine to tryptophan ratio (K/T ratio) is a potential biomarker for TB diagnosis and treatment response but has not been assessed in children.MethodsWe performed a targeted diagnostic accuracy analysis of four biomarkers: kynurenine abundance, tryptophan abundance, the K/T ratio, and IDO-1 gene expression. Data were obtained from transcriptome and metabolome profiling of children with confirmed tuberculosis and age- and sex-matched uninfected household contacts of pulmonary tuberculosis patients. Each biomarker was assessed as a baseline diagnostic and in response to successful TB treatment.ResultsDespite non-significant between-group differences in unbiased analysis, the K/T ratio achieved an area under the receiver operator characteristic curve (AUC) of 0.667 and 81.5% sensitivity for TB diagnosis. Kynurenine, tryptophan, and IDO-1 demonstrated diagnostic AUCs of 0.667, 0.602, and 0.463, respectively. None of these biomarkers demonstrated high AUCs for treatment response. The AUC of the K/T ratio was lower than biomarkers identified in unbiased analysis, but improved sensitivity over existing commercial assays for pediatric TB diagnosis.ConclusionsPlasma kynurenine and the K/T ratio may be useful biomarkers for pediatric TB. Ongoing studies in geographically diverse populations will determine optimal use of these biomarkers worldwide.

Associated risk factor of tuberculosis infection among adult patients in Gedeo Zone, Southern Ethiopia.

Background:Tuberculosis remains a major global health problem causing death among millions of people each year. Even though many of the World Health Organization recommended tuberculosis control strategies were implemented, there is still a major gap in tuberculosis case detection and treatment which resulted in rapid transmission of the cases in high burden countries. This study aimed to provide updated information on the contributing factors for the development of tuberculosis.Methods:A case–control study was carried out in Gedeo Zone from February to July 2021 to assess the risk factors of tuberculosis. Cases were confirmed pulmonary tuberculosis patients with age ⩾18 years, while controls were participants who were confirmed to be pulmonary tuberculosis negative with the same age. Multivariate logistic regression models were used to assess the associated risk factor.Results:A total of 368 individuals (173 cases and 173 controls) were included in this study. Based on the multivariable logistic regression analysis, we identified six variables as independent risk factors for the development of tuberculosis after controlling possible confounders. Those were patients with income <1500 Ethiopian birr per month (adjusted odds ratio = 2.35; 95% confidence interval: 1.22–3.97), patients with no educational background (illiterate) (adjusted odds ratio = 2.10; 95% confidence interval: 1.17–2.51), patients smoking cigarette (adjusted odds ratio = 2.89; 95% confidence interval: 2.10–3.82), patients chewing khat (adjusted odds ratio = 2.86; 95% confidence interval: 1.28–3.79), patients in close contact with known tuberculosis cases (adjusted odds ratio = 3.63; 95% confidence interval: 2.24–4.46), and patients being positive for HIV (adjusted odds ratio = 3.01; 95% confidence interval: 1.07–3.52) who were found to be significantly associated with tuberculosis development, while Bacille Calmette-Guérin vaccination had a protective effect against the development of tuberculosis (adjusted odds ratio = 0.52; 95% confidence interval: 0.21–0.88).Conclusion:The priority should be given to the identified contributing factors through application of coordinated efforts on screening of patients suspected for pulmonary tuberculosis and all contacts of pulmonary tuberculosis patients and treatment of known tuberculosis cases, and appropriate control methods to reduce Mycobacterium tuberculosis cases.

Challenges Faced by House-Hold Contacts of Pulmonary Tuberculosis Patients In An Urban Setting In Nairobi, Kenya

Close contacts of active pulmonary tuberculosis (PTB) patients are at higher risk of infection as the confirmed cases remain highly infectious before and while in the early stages of treatment. This work highlights the encounters and perspectives of household contacts (HHCs) of PTB patients in an urban setting in Kenya, with a focus on accessibility to health services, interactions within the community, and the risk of infection at home. A multimethod study design involving descriptive cross-sectional analysis and informal interviews was used. The study participants were recruited from tuberculosis (TB) isolation wards and outpatient clinics of Mbagathi County Hospital in Nairobi, Kenya. Data was collected using structured questionnaires and informal interviews. Results revealed improved access to treatment by PTB patients. However, the global goal of eliminating TB infections by minimizing latent tuberculosis reactivation remains a challenge in this population primarily because most of the HHCs lacked knowledge on diagnosis and treatment of latent tuberculosis infection (LTBI). Most participants were residents of informal settlements in Nairobi characterized by small and poorly planned housing structures with poor waste management systems. In most houses, the living space doubled as cooking and sleeping area. There was therefore a high exposure of spouses, children and other persons living with the patients. We recommend that further education be provided to HHCs to increase awareness on available testing and preventive treatment for LTBI, and infection prevention practices at the household level. Furthermore, additional resources should be offered to economically disadvantaged patients to support their social and treatment needs.

Tuberculosis screening in household contacts of pulmonary tuberculosis patients in an urban setting.

BackgroundHousehold contacts (HHC) of tuberculosis (TB) patients are at risk of TB infection and disease. The study assessed the utility of “Household contact card and register” for screening of HHC of pulmonary TB (PTB) patients for TB and explored the reasons for HHC not being screened and followed-up.MethodsThe “Household contact card and register” was implemented by the Health Care Workers (HCW) of the TB Control Programme in Chennai District for screening HHC of index PTB patients initiated on treatment between June and August, 2018. Contacts were required to be screened within 2 months of treatment initiation of the index patient. Details collected included age, gender, smoking, alcohol use, immunosuppressive conditions and TB treatment. Symptom screening along with chest radiograph and or sputum examination was attempted. Follow-up TB screening at 6 and 12 months were performed. Screening of HHC was compared pre and post implementation phase. Proportions were computed for the data analysed.ResultsHHC information was documented for 93% (1268/1364) of Index PTB patients. The main reasons of non-listing of HHC in 96 PTB patients were HCW non-availability or non-co-operation of the HHC. There were 2150 (80%) contacts who were screened for TB. Inconvenient time, feeling healthy, stigma, out-station visit were the main reasons for 537 contacts not undergoing TB screening. Anti-TB treatment was initiated in 21 (1%) of contacts diagnosed with TB. Preventive therapy was initiated in 59% (81/138) of contacts aged <6 years. The screening of HHC improved from 36% to 80% during the implementation phase. Follow-up TB screening at 12 months was performed in 50% of HHC and 2 incident TB cases were identified.Conclusion“Household contact card and register” is a useful tool for HCWs for TB screening in HHC of PTB patients. Reasons for non-adherence to contact screening needs to be addressed.

Tuberculosis preventive treatment should be considered for all household contacts of pulmonary tuberculosis patients in India.

The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

Infectiousness of patients with smear-negative pulmonary tuberculosis, assessed by Real-time Polymerase Chain Reaction, XpertⓇMTB/RIF

Currently, pulmonary tuberculosis (TB) isolation recommendations are based on serial sputum smear microscopy. To assess infectiousness of smear-negative/GeneXpert-positive (Sm-/GXpert+) pulmonary TB, we evaluated 511 contacts of pulmonary TB patients attended at a teaching hospital in Spain (2010–2018). There were no statistically significant differences in rates of Mycobacterium tuberculosis infection (46.2% contacts of smear-positive and 34.6% contacts of Sm-/GXpert+ pulmonary TB patients, p = 0.112). Sm-/GXpert+ pulmonary TB poses a substantial risk of transmission of M. tuberculosis infection. Our results add evidence to support including Real-time Polymerase Chain Reaction (XpertⓇMTB/RIF) in the work-up diagnosis of suspected pulmonary TB cases to make decisions on air-borne isolation.

Risk of infection and disease progression in children exposed to tuberculosis at home, Colombia.

Aim: To assess the risk of tuberculosis (infection and disease) in children less than 15 years’ old who are household contacts of pulmonary tuberculosis patients in three Colombian cities (Medellín, Cali, and Popayán). Methods: A cohort of 1,040 children household contacts of 380 adults with smear-positive pulmonary tuberculosis was followed up for 24 months. Study period 2005-2009. Results: Tuberculin skin test was positive (≥10 mm) in 43.7% (95% CI: 39.2-48.2). Tuberculin skin test positivity was associated with age 10-14 years (Prevalence Ratio -PR= 1.43, 95% CI: 1.1-1.9), having a BCG vaccine scar (PR= 1.52, 95% CI: 1.1-2.1), underweight, closer proximity to the index case and exposure time >3 months. The annual risk of infection (tuberculin skin test induration increase of 6 mm or more per year) was 17% (95% CI: 11.8-22.2) and was associated with a bacillary load of the adult index case (Relative Risk -RR= 2.12, 95% CI: 1.0-4.3). The incidence rate of active tuberculosis was 12.4 cases per 1,000 persons-year. Children <5 years without BCG vaccine scar had a greater risk of developing active disease (Hazard Ratio -HR= 6.00, 95% CI: 1.3-28.3) than those with scar (HR= 1.33, 95% CI: 0.5-3.4). The risk of developing active tuberculosis augmented along with the increase from initial tuberculin skin test (tuberculin skin test 5-9 mm HR= 8.55, 95% CI: 2.5-29.2; tuberculin skin test ≥10 mm HR= 8.16, 95% CI: 2.0-32.9).Conclusions: There is a need for prompt interruption of adult-to-children tuberculosis transmission within households. Conducting proper contact investigation and offering chemoprophylaxis to infected children could reduce tuberculosis transmission.

Tuberculin skin test and QuantiFERON-Gold In Tube assay for diagnosis of latent TB infection among household contacts of pulmonary TB patients in high TB burden setting.

BackgroundWorld Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.Materials and methodsA prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ≥0.35 IU/ml and a positive TST as an induration of ≥5 mm. A secondary outcome of TST induration ≥10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.ResultsOf 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15–40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.ConclusionPrevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.

Investigation of household contacts of pulmonary tuberculosis patients increases case detection in Mwanza City, Tanzania

BackgroundTuberculosis (TB) contact tracing is a key strategy for containing TB and provides addition to the passive case finding approach. However, this practice has not been implemented in Tanzania, where there is unacceptably high treatment gap of 62.1% between cases estimated and cases detected. Therefore calls for more aggressive case finding for TB to close this gap. We aimed to determine the magnitude and predictors of bacteriologically-confirmed pulmonary TB among household contacts of bacteriologically-confirmed pulmonary TB index cases in the city of Mwanza, Tanzania.MethodsThis study was carried out from August to December 2016 in Mwanza city at the TB outpatient clinics of Tertiary Hospital of the Bugando Medical Centre, Sekou-Toure Regional Hospital, and Nyamagana District Hospital. Bacteriologically-confirmed TB index cases diagnosed between May and July 2016 were identified from the laboratory registers book. Contacts were traced by home visits by study TB nurses, and data were collected using a standardized TB screening questionnaire. To detect the bacterioriologically-confirmed pulmonary TB, two sputum samples per household contact were collected under supervision for all household contacts following standard operating procedures. Samples were transported to the Bugando Medical Centre TB laboratory for investigation for TB using fluorescent smear microscopy, GeneXpert MTB/RIF and Löwenstein–Jensen (LJ) culture. Logistic regression was used to determine predictors of bacteriologically-confirmed pulmonary TB among household contacts.ResultsDuring the study period, 456 household contacts from 93 TB index cases were identified. Among these 456 household contacts, 13 (2.9%) were GeneXpert MTB/RIF positive, 18 (3.9%) were MTB-culture positive and four (0.9%) were AFB-smear positive. Overall, 29 (6.4%) of contacts had bacteriologically-confirmed pulmonary TB. Predictors of bacteriologically-confirmed pulmonary TB among household contacts were7being married (Odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4–8.0; p = 0.012) and consuming less than three meals a day (OR, 3.7; 95% CI, 1.6–8.7; p = 0.009).ConclusionsOur data suggest that in Mwanza, Tanzania, seven in 100 contacts living in the same house with a TB patient develop bacteriologically-confirmed pulmonary TB. These results therefore underscore the need to implement routine TB contact tracing to control tuberculosis in high TB burden countries such as Tanzania.