Elucidating the effect of pro and anti-inflammatory recombinant cytokines TNF-α and TGF-ß 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-ß were significantly low in APTB when compared to HHC and HC with p < 0.0376, p < 0.0247 respectively, and TGF-ß 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.

Comparison of the yield of two tuberculosis screening approaches among household contacts in a community setting of Silti Zone, Central Ethiopia: a prospective cohort study.

BACKGROUND: Household contacts of tuberculosis (TB) patients are at a greater risk of infection and developing TB as well. Despite recommendations to actively screen such high-risk groups for TB, it is poorly implemented in Ethiopia. A community-based household contact screening was conducted to compare the yield of two different screening approaches and to identify factors associated with TB occurrence. METHODS: Smear-positive pulmonary TB index cases from six health facilities in six districts of Silti Zone were identified and enrolled prospectively between September 2020 and December 2022. Trained healthcare workers conducted house visits to screen household contacts for TB. WHO (World Health Organization) recommended symptom-based screening algorithms were used. The yield of screening was compared between a two-time screening at study site I and a single baseline screening at study site II, which is the current programmatic approach. Generalized estimating equation was used to run multivariate logistic regression to identify factors associated with TB occurrence. RESULTS: A total of 387 index TB cases (193 at site I and 194 at site II) with 1,276 eligible contacts were included for analysis. The TB yield of repeat screening approach did not show a significant difference compared to a single screening (2.3% at site I vs. 1.1% at site II, p < 0.072). The number needed to screen was 44 and 87 for the repeat and single screening, respectively, indicating a high TB burden in both settings. The screening algorithm for patients with comorbidities of asthma and heart failure had a 100% sensitivity, 19.1% specificity and a positive predictive value of 5.6%. Cough [AOR: 10.9, 95%CI: 2.55,46.37], fatigue [AOR: 6.1, 95%CI: 1.76,21.29], daily duration of contact with index case [AOR: 4.6, 95%CI; 1.57,13.43] and age of index cases [AOR: 0.9, 95%CI; 0.91-0.99] were associated with the occurrence of TB among household contacts. CONCLUSION: Our study showed that the yield of TB was not significantly different between one-time screening and repeat screening. Although repeat screening has made an addition to case notification, it should be practiced only if resources permit. Cough, fatigue, duration of contact and age of index cases were factors associated with TB. Further studies are needed to establish the association between older age and the risk of transmitting TB.

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.

Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial.

Background: In a cluster randomized trial (clinicaltrials.gov: NCT02810678) a flexible but comprehensive health system intervention significantly increased the number of household contacts (HHC) identified and started on tuberculosis preventive treatment (TPT). A follow-up study was conducted one year later to test the hypotheses that these effects were sustained, and were reproducible with a simplified intervention. Methods: We conducted a follow-up study from May 1, 2018 until April 30, 2019, as part of a multinational cluster randomized trial. Eight sites in 4 countries that had received the intervention in the original trial received no further intervention; eight other sites in the same countries that had not received the intervention (control sites in the original trial) now received a simplified version of the intervention. This consisted of repeated local evaluation of the Cascade of care for TB infection, and stakeholder decision making. The number of HHC identified and starting TPT were repeatedly measured at all 16 sites and expressed as rates per 100 newly diagnosed index TB patients. The sustained effect of the original intervention was estimated by comparing these rates after the intervention in the original trial with the last 6 months of the follow-up study. The reproducibility was estimated by comparing the pre-post intervention changes in rates at sites receiving the original intervention with the pre-post changes in rates at sites receiving the later, simplified intervention. Findings: With regard to the sustained impact of the original intervention, compared to the original post-intervention period, the number of HHC identified and treated per 100 newly diagnosed TB patients was 10 more (95% confidence interval: 84 fewer to 105 more), and 1 fewer (95% CI: 22 fewer to 20 more) respectively up to 14 months after the end of the original intervention. With regard to the reproducibility of the simplified intervention, at sites that had initially served as control sites, the number of HHC identified and treated per 100 TB patients increased by 33 (95% CI: -32, 97), and 16 (-69, 100) from 3 months before, to up to 6 months after receiving a streamlined intervention, although differences were larger, and significant if the post-intervention results were compared to all pre-intervention periods. Interpretation: Up to one year after it ended, a health system intervention resulted in sustained increases in the number of HHC identified and starting TPT. A simplified version of the intervention was associated with non-significant increases in the identification and treatment of HHC. Inferences are limited by potential bias due to other temporal effects, and the small number of study sites. Funding: Funded by the Canadian Institutes of Health Research (Grant number 143350).

Absence of short-term changes in knowledge and attitudes among household contacts of COVID-19 cases during the post-acute phase of the pandemic in Catalonia and Navarre, Spain.

Objectives: To evaluate short-term changes in knowledge and attitude towards COVID-19 and preventive measures during the post-acute phase of the pandemic in Spain. Methods: A survey was performed in Catalonia and Navarre between May-2022 and July-2023 in household contacts of COVID-19 cases. Knowledge and attitude were assessed at baseline and at three months, using a Likert scale. Responses were grouped according to correct or incorrect. Results: At baseline, 172 subjects were contacted, 118 (69%) of which completed a follow-up interview three months later. Knowledge of correct hand-washing and mask protocols had maintained over time (-1.7%, p = 0.553 and - 2.5%, p = 0.473, respectively). Attitudes toward preventive measures was adequate in the first interview (86%), but attitudes regarding use of face masks decreased significantly (-9.1%, p = 0.048) over time in participants with higher risk of severe COVID-19. However, most short-term changes in knowledge and attitudes were not statistically significant. Conclusion: Household contacts showed correct knowledge and attitude towards COVID-19 and its preventive measures, without significant changes in the short term despite a relaxation of government-mandated preventive measures. These results provide relevant information in case of a new health emergency due to respiratory viruses.

Hepatitis B virus infection, associated factors, knowledge and vaccination status among household contacts of hepatitis B index cases in Mwanza, Tanzania.

Objectives: To determine the prevalence of hepatitis B virus (HBV) infection, knowledge regarding HBV, vaccination status, and associated factors among household contacts of HBV index cases in Mwanza, Tanzania. Methods: Between July and August 2023, a cross-sectional study involving 97 index cases and 402 household contacts was conducted. Data were collected using pre-tested structured questionnaire and blood samples were collected from household contacts for HBV surface antigen (HBsAg) testing. Results: The prevalence of HBV among household contacts was 5.4% (95% confidence interval, 2.9-9.0) with a significantly high proportion observed in > 45 years (16.6%) and in males (9.9%). A total of 40.0% of the household contacts had completed the full HBV vaccination series. On multivariate analysis, being male was significantly associated with HBsAg positivity (odds ratio: 7.16, 95% confidence interval: 1.81-28.2, P = 0.005). Conclusion: About one-tenth of adults' male household contacts were HBsAg positive. In addition, the majority of household contacts had poor to fair knowledge regarding HBV infection with more than half being unvaccinated against HBV. There is a need to enhance awareness and education regarding HBV infection among household contacts in Tanzania and other low- and middle-income countries.

The Invisible Toll: Unveiling the Prevalence and Predictors of Depression and Anxiety Among Pulmonary Tuberculosis (TB) Patients and Their Households in Gujarat, India.

BACKGROUND:  Tuberculosis (TB) imposes a substantial physical and psychological burden on patients and their families. This study aimed to investigate the prevalence and predictors of depression and anxiety among pulmonary TB patients and their household contacts in Jamnagar, Gujarat, India. MATERIALS AND METHODS:  A cross-sectional study was conducted at TB units (TUs) in Jamnagar, Gujarat. Trained research assistants interviewed 272 pulmonary TB patients and 544 household contacts using structured questionnaires. Depression and anxiety were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Hamilton Anxiety Rating Scale (HAM-A), respectively. Sociodemographic, clinical, and psychosocial factors (stigma and social support) were evaluated. Logistic regression analyses were performed to identify predictors of depression and anxiety. A p-value of < 0.05 was considered statistically significant for all analyses in this study. RESULTS:  Out of 272 TB patients and 544 household contacts, the prevalence of depression was 98 (36.0%) and 135 (24.8%) (p=0.001). Anxiety was present in 85 (31.3%) of TB patients and 112 (20.6%) of household contacts (p<0.001). For TB patients, low household income (AOR=2.1, 95% CI: 1.9-4.3), low social support (AOR=0.84, 95% CI: 0.6-0.9), and high perceived stigma (AOR=2.3, 95% CI: 1.3-4.5) were independently associated with depression. Among household contacts, similar factors were identified, including low household income (AOR=1.7, 95% CI: 1.6-2.9), low social support (AOR=0.88, 95% CI: 0.6-0.9), and high perceived stigma (AOR=1.80, 95% CI: 1.1-2.3). CONCLUSION:  Depression and anxiety are highly prevalent among pulmonary TB patients and their household contacts in Gujarat, India. Low socioeconomic status, lack of social support, and TB-related stigma emerged as significant predictors of these mental health conditions, underscoring the need for integrated, multidisciplinary interventions to address the psychological impact of TB on patients and their families.

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

Background: 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. Objective: To explore the knowledge, attitude, and practice (KAP) toward TB prevention and management among household contacts of TB patients. Methods: 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. Results: 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. Conclusion: 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.

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.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Mental Health Impacts of Multidrug-Resistant Tuberculosis in Patients and Household Contacts: A Mixed Methods Study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) patients experience disproportionately worse mental health, with implications for adherence, outcomes, and families. Comprehensive assessments of comorbid depression/anxiety and related factors remain limited. OBJECTIVE: This study aimed to assess the prevalence, predictors, and qualitative experiences of depression and anxiety in MDR-TB patients and household contacts. METHODS: A sequential explanatory mixed methods study was conducted in Gujarat, India, with 403 smear-positive MDR-TB patients and 403 contacts. The quantitative phase administered structured questionnaires on sociodemographic factors, clinical history, depression/anxiety symptoms, and psychosocial stressors (like stigma and social support). Logistic regression models were used. The qualitative phase included in-depth interviews with 30 purposively sampled patients for thematic content analysis. Results were integrated to contextualize quantitative findings. RESULTS: High rates of depression (37.5%, n = 151) and anxiety (45.2%, n = 182) were documented among the MDR-TB patients, significantly greater than household contacts (20.1%, n = 81 and 25.1%, n = 101, respectively). For depression, older age (adjusted odds ratio (AOR) 2.03, 95% CI 1.01-4.05), female gender (AOR 2.5, 95% CI 1.1-6.0), divorced/widowed status (AOR 3.8, 95% CI 1.1-8.0), financial constraints, substance abuse (AOR 1.7, 95% CI 1.1-2.7), greater disease severity (AOR 1.8, 95% CI 1.5-2.2), medication side effects (AOR 2.4, 95% CI 1.2-4.6), and perceived stigma (AOR 3.2, 95% CI 1.1-5.3) emerged as significant risk factors. For anxiety, significant predictors were less social support (AOR 0.81, 95% CI 0.71-0.86), higher perceived stigma (AOR 2.2, 95% CI 1.1-6.3), greater disease severity (AOR 2.6, 95% CI 1.3-4.0), and more medication side effects (AOR 3.3, 95% CI 1.1-5.5). Prominent themes included psychological impacts like depression and anxiety, experiences of stigma and caretaking challenges, and recommendations for comprehensive patient support services. CONCLUSION: MDR-TB patients experience a substantially higher dual disease burden of depression and anxiety, elevating the risk for adverse outcomes and transmission. Improving psychosocial support is vital to patient-centric care pathways for vulnerable groups. Mixed methods provide comprehensive evidence to inform integrated physical and mental health services.

Single-Dose Rifampicin Leprosy Chemoprophylaxis for Household Contacts in Kiribati: An Audit of a Combined Retrospective and Prospective Approach.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, an SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases retrospectively (2010-2017) and prospectively (2018-2022). We conducted a retrospective audit to determine the comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,641 household contacts were identified (9791 in the retrospective and 3850 in the prospective cohort). In the retrospective cohort, 1044 (11%) contacts were absent, 403 (4%) were ineligible for SDR, and 42 new cases were detected (0.4%) Overall, SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR, and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were 23 SDR refusals. The median time to SDR administration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts, respectively. SDR was readily accepted in both cohorts. The new case detection rate (0.5%) is consistent with that in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

Comparison of antiphenolic glycolipid-1 antibody levels in seropositive contacts of leprosy after 2 years of single-dose rifampicin as postexposure prophylaxis.

Background: Leprosy is still a global problem, especially in developing countries, including Indonesia. Ineffective prevention of leprosy leads to active transmission of the disease. World Health Organization (WHO) recommend post-exposure prophylaxis (PEP) with single dose of rifampicin (SDR) for leprosy patients. Previous study showed protective effect of SDR against leprosy, especially for the first 2 years. Hence, the use of PEP and IgM anti PGL-1 examination are required to suspend the chain of leprosy transmission. This study evaluated the effectiveness of SDR administration by comparing IgM anti-PGL-1 antibody levels in seropositive household contacts before and after 2 years of SDR administration. Methods: Analytical observational laboratory study comparing IgM anti PGL-1 antibody levels before and after 2 years of SDR administration in leprosy contacts, with a prospective follow-up study design. We conducted this study from December 2022 to January 2023 at Dr. Mohammad Hoesin General Hospital Palembang. All seropositive household contacts of leprosy who had been administrated SDR 2 years ago were included, then PGL-1 antibody levels were examined. Results: The use of SDR showed significant improvement in leprosy contacts after 2 years (P=0.000). The median antibody level before SDR administration was 1,209.20 (615.81 - 4,353.60), which decrease to 146.03 (0 - 2,487.80) U/mL after 2 years. There was statistically significant relationship between history of BCG vaccination (P=0.003) and IgM PGL-1 antibody levels after 2 years of SDR administration. Conclusion: There is a significant decrease in IgM anti PGL-1 antibody levels among leprosy contacts after 2 years of SDR chemoprophylaxis administration.

Tuberculosis preventive treatment in children and adolescents: an observational study of secondary data

Abstract Objective To analyze the effectiveness, safety, outcomes, and associated factors of tuberculosis preventive treatment (TPT) in children and adolescents in Paraná, southern Brazil. Method This was an observational cohort study with a retrospective collection of secondary data from the TPT information systems of the state of Paraná from 2009 to 2016, and tuberculosis in Brazil from 2009 to 2018. Results In total, 1,397 people were included. In 95.4% of the individuals, the indication for TPT was a history of patient-index contact with pulmonary tuberculosis. Isoniazid was used in 99.9% of the cases with TPT, and 87.7% completed the treatment. The TPT protection was 98.7%. Among the 18 people who had TB, 14 (77.8%) became ill after the second year of treatment, and four (22.2%) in the first two years (p < 0.001). Adverse events were reported in 3.3% of cases, most of them were gastrointestinal and medication was discontinued in only 2 (0.1%) patients. No risk factors associated with the illness were observed. Conclusions The authors observed a low rate of illness in pragmatics routine conditions in TPT for children and adolescents, especially within the first two years after the end of treatment, with good tolerability and a good percentage of adherence to the treatment. TPT should be encouraged to achieve the goals of the End TB Strategy of the World Health Organization as an essential strategy to reduce the incidence rate of the disease, but studies with new schemes must continue to be carried out in real-life scenarios.

Factors associated with seropositivity for APGL-Iamong household contacts of leprosy patients

Abstract: INTRODUCTION: Leprosy is mainly transmitted among family members who share genetic and ambient factors. The clinical form of leprosy in the index case and kinship could be risk factors for leprosy transmission. High antibody levels in household contacts (HC) in the absence of neural or skin lesions may characterize latent infection. This study aimed to evaluate the association between seropositivity for anti-phenolic glycolipid-I immunoglobulin M antibodies (APGL-I) in HC and the clinical classification of the index case and to analyze the association between APGL-I positivity with other factors such as age, kinship, and gender. METHODS: We performed a survey among 320 HC of 120 leprosy patients who were evaluated and followed-up in a leprosy outpatient clinic of a university hospital. All HC underwent complete skin examination, peripheral nerve palpation, skin sensory tests, and serologic tests for the detection and quantification of APGL-I. RESULTS: The overall seropositivity rate was 20%, and was greatly affected by kinship. APGL-I seropositivity was higher in siblings (41%), followed by parents (28%), spouses (26%), other (19%), and offspring (14%). Independent risk factors for seropositivity were being siblings (OR 3.3) and being a HC of an index case with indeterminate leprosy (OR 5.3). APGL-I seropositivity was associated with index cases with a bacillary index of 4 (88%; p<.001). Seropositivity among HC was not significantly associated with their gender and age. There was no statistical difference in the seropositivity rates of HC of index patients with paucibacillary and multibacillary leprosy. CONCLUSIONS: Strict evaluation and follow-up of HC with positive results for APGL-I is recommended. Special attention should be paid during the screening of siblings of the index cases, HC of patients with a high bacillary index, and HC of patients with indeterminate leprosy.