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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Socio-economic burden of TB and its impact on child contacts in The Gambia.

OBJECTIVE: To determine the social impact of adult TB on child household contacts living in the Greater Banjul Area, The Gambia. METHODS: This was a prospective observational cohort study among adults (≥18 years) starting treatment for drug-susceptible pulmonary TB between June 2019 and July 2021 who reported having at least one child household contact. We collected data from 51 adults and 180 child contacts at the start of TB treatment (baseline) and again at 6 months of treatment. Participants were asked about expenses for school fees, healthcare, festivities and food security of child contacts. RESULTS: While school attendance of the child contacts remained largely unaffected, there was a significant drop in school performance at 6 months (P < 0.001). Furthermore, child contacts faced significant food insecurity in terms of food quantity and variety available, with up to a four-fold increase in some instances at 6 months compared to baseline (P < 0.001). CONCLUSION: Child contacts face a potential decline in school performance and risk of food insecurity. While a plethora of work is being undertaken to alleviate costs of care for TB patients, further emphasis is needed to ensure educational and social prosperity for child contacts, as adults with TB have socio-economic implications for the wider household.

OBJECTIF: Déterminer l'impact social de la TB de l'adulte sur les contacts familiaux de l'enfant vivant dans la région du Grand Banjul, en Gambie. MÉTHODES: Il s'agissait d'une étude de cohorte observationnelle prospective auprès d'adultes (≥18 ans) commençant un traitement contre la TB pulmonaire sensible aux médicaments entre juin 2019 et juillet 2021 et qui ont déclaré avoir au moins un contact domestique avec un enfant. Nous avons recueilli des données auprès de 51 adultes et 180 enfants contacts au début du traitement contre la TB, puis à nouveau après 6 mois de traitement. Les participants ont été interrogés sur les dépenses liées aux frais de scolarité, aux soins de santé, aux célébrations et à la sécurité alimentaire des enfants contacts. RÉSULTATS: Alors que la fréquentation scolaire des enfants contacts n'a pratiquement pas été affectée, on a constaté une baisse significative des résultats scolaires 6 mois plus tard (P < 0,001). Par ailleurs, les enfants contacts ont été confrontés à une insécurité alimentaire importante en termes de quantité et de variété de nourriture disponible, avec une augmentation d'au moins quatre fois après le traitement de la TB (P < 0,001). CONCLUSION: Les enfants contacts sont confrontés à une baisse potentielle de leurs résultats scolaires et à un risque d'insécurité alimentaire. Alors qu'une multitude de travaux sont entrepris pour réduire les coûts des soins pour les patients atteints de TB, il est nécessaire de mettre davantage l'accent sur la prospérité éducative et sociale des enfants contacts, étant donné que les adultes atteints de TB ont des implications socio-économiques pour l'ensemble du ménage.

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.

Transmissibility of severe acute respiratory syndrome coronavirus 2 among household contacts of coronavirus disease 2019-positive patients: A community-based study in India.

BACKGROUND: This study identified the risk factors for severe acute respiratory syndrome coronavirus 2 infection among household contacts of index patients and determined the incubation period (IP), serial interval, and estimates of secondary infection rate in Kerala, India. METHODS: We conducted a cohort study in three districts of Kerala among the inhabitants of households of reverse transcriptase polymerase chain reaction-positive coronavirus disease 2019 patients between January and July 2021. About 147 index patients and 362 household contacts were followed up for 28 days to determine reverse transcriptase polymerase chain reaction positivity and the presence of total antibodies against SARS-CoV-2 on days 1, 7, 14, and 28. RESULTS: The mean IP, serial interval, and generation time were 1.6, 3, and 3.9 days, respectively. The secondary infection rate at 14 days was 43.0%. According to multivariable regression analysis persons who worked outside the home were protected (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.24-0.85), whereas those who had kissed the coronavirus disease 2019-positive patients during illness were more than twice at risk of infection (aOR, 2.23; 95% CI, 1.01-5.2) than those who had not kissed the patients. Sharing a toilet with the index patient increased the risk by more than twice (aOR, 2.5; 95% CI, 1.42-4.64) than not sharing a toilet. However, the contacts who reported using masks (aOR, 2.5; 95% CI, 1.4-4.4) were at a higher risk of infection in household settings. CONCLUSIONS: Household settings have a high secondary infection rate and the changing transmissibility dynamics such as IP, serial interval should be considered in the prevention and control of SARS-CoV-2.

Gut microbiome dynamics in index patients colonized with extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales after hospital discharge and their household contacts.

IMPORTANCE: Colonization with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) often precedes infections and is therefore considered as a great threat for public health. Here, we studied the gut microbiome dynamics in eight index patients colonized with ESBL-PE after hospital discharge and the impact of exposure to this index patient on the gut microbiome dynamics of their household contacts. We showed that the microbiome composition from index patients is different from their household contacts upon hospital discharge and that, in some of the index patients, their microbiome composition over time shifted toward the composition of their household contacts. In contrast, household contacts showed a stable microbiome composition over time irrespective of low-level extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) or extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-Kp) gut colonization, suggesting that, in healthy microbiomes, colonization resistance is able to prevent ESBL-PE expansion.

Specialized active leprosy search strategies in an endemic area of the Brazilian Amazon identifies a hypermutated Mycobacterium leprae strain causing primary drug resistance.

Introduction: Leprosy, an infectious disease caused by Mycobacterium leprae, remains a public health concern in endemic countries, particularly in Brazil. In this study, we conducted an active surveillance campaign in the hyperendemic city of Castanhal in the northeastern part of the state of Pará using clinical signs and symptoms combined with serological and molecular tools to diagnose new cases and to identify drug resistance of circulating M. leprae strains and their distribution in the community. Methods: During an active surveillance of one week, we enrolled 318 individuals using three different strategies to enroll subjects for this study: (i) an active survey of previously treated cases from 2006 to 2016 found in the Brazil National Notifiable Disease Information System database (n = 23) and their healthy household contacts (HHC) (n = 57); (ii) an active survey of school children (SC) from two primary public schools in low-income neighborhoods (n = 178), followed by visits to the houses of these newly diagnosed SC (n = 7) to examine their HHC (n = 34) where we diagnosed additional new cases (n = 6); (iii) and those people who spontaneously presented themselves to our team or the local health center with clinical signs and/or symptoms of leprosy (n = 6) with subsequent follow-up of their HHC when the case was confirmed (n = 20) where we diagnosed two additional cases (n = 2). Individuals received a dermato-neurological examination, 5 ml of peripheral blood was collected to assess the anti-PGL-I titer by ELISA and intradermal earlobe skin scrapings were taken from HHC and cases for amplification of the M. leprae RLEP region by qPCR. Results: Anti-PGL-I positivity was highest in the new leprosy case group (52%) followed by the treated group (40.9%), HHC (40%) and lowest in SC (24.6%). RLEP qPCR from SSS was performed on 124 individuals, 22 in treated cases, 24 in newly diagnosed leprosy cases, and 78 in HHC. We detected 29.0% (36/124) positivity overall in this sample set. The positivity in treated cases was 31.8% (7/22), while in newly diagnosed leprosy cases the number of positives were higher, 45.8% (11/23) and lower in HHC at 23.7% (18/76). Whole genome sequencing of M. leprae from biopsies of three infected individuals from one extended family revealed a hypermutated M. leprae strain in an unusual case of primary drug resistance while the other two strains were drug sensitive. Discussion: This study represents the extent of leprosy in an active surveillance campaign during a single week in the city of Castanhal, a city that we have previously surveyed several times during the past ten years. Our results indicate the continuing high transmission of leprosy that includes fairly high rates of new cases detected in children indicating recent spread by multiple foci of infection in the community. An unusual case of a hypermutated M. leprae strain in a case of primary drug resistance was discovered. It also revealed a high hidden prevalence of overt disease and subclinical infection that remains a challenge for correct clinical diagnosis by signs and symptoms that may be aided using adjunct laboratory tests, such as RLEP qPCR and anti-PGL-I serology.

SARS-CoV-2 risk in household contacts of healthcare workers: a prospective cohort study.

BACKGROUND: Few studies have assessed whether the increased SARS-CoV-2 risk of healthcare workers (HCW) is carried on to their household contacts. Within a prospective HCW cohort, we assessed the SARS-CoV-2 risk of household contacts of HCW depending on the HCWs cumulative exposure to COVID-19 patients and identified factors influencing this association. METHODS: HCW aged ≥ 16 years from nine Swiss healthcare networks participated. HCW without any household contacts were excluded. For HCW, cumulative patient exposure (number of COVID-19 patient contacts times average contact duration during a 12-month follow-up) was calculated. During follow-up, HCW reported SARS-CoV-2 nasopharyngeal swab results and positive swab results of their household contacts. We used multivariable logistic regression to identify variables associated with SARS-CoV-2 household positivity. RESULTS: Of 2406 HCW, 466 (19%) reported ≥ 1 SARS-CoV-2 positive household. In multivariable analysis, patient exposure of HCW (adjusted OR [aOR] 1.08 per category, 95% CI 1.04-1.12), household size (aOR 1.53 per household member, 95% CI 1.35-1.73) and having children (aOR 0.70, 95% CI 0.53-0.94) remained associated with household positivity. Vaccinated HCW had a lower risk (aOR 0.54, 95% CI 0.38-0.77) of reporting a positive contact, as were those using respirator masks in contact with COVID-19 patients (aOR 0.65, 95% CI 0.49-0.86). Among vaccinated HCW, delayed first vaccination was associated with increased household SARS-CoV-2 positivity (aOR 1.14 per month, 95% CI 1.08-1.21). CONCLUSIONS: SARS-CoV-2 positivity in household contacts of HCW increases with higher cumulative COVID-19 patient exposure of HCWs. Measures reducing the SARS-CoV-2 risk in HCW might indirectly reduce the infection risk of their households.

Polyunsaturated Fatty Acid-Derived Lipid Mediators as Potential Biomarkers for Leprosy Among Individuals with Asymptomatic Mycobacterium leprae Infection.

Intra-household contacts (HCs) of leprosy patients are at increased risk of infection by Mycobacterium leprae and about ∼5-10% will develop active disease. A prognostic tool to identify HCs with the greatest risk of progressing to active disease would enhance early leprosy diagnosis and optimize prophylactic intervention. Previous metabolomics studies suggest that host lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are potential biomarkers for leprosy. In this study, we investigated retrospective sera of leprosy HCs by liquid chromatography-mass spectrometry and enzyme-linked immunoassay to determine whether circulating levels of ω-3 and ω-6 PUFA metabolites were altered in HCs that developed leprosy (HCDL) in comparison to those that did not (HCNDL). Sera were collected from HCs at the time of index case diagnosis and before clinical signs/symptoms of leprosy. Our findings showed that HCDL sera exhibited a distinct metabolic profile in comparison to HCDNL. Specifically, arachidonic acid, leukotriene B4, 11-hydroxyeicosatetraenoic acid, prostaglandin D2, and lipoxin A4 were elevated in HCDL. In contrast, prostaglandin E2 levels were reduced in HCDL. The ω-3 PUFAs, docosahexaenoic acid, eicosapentaenoic acid, and the docosahexaenoic acid-derived resolvin D1 and maresin-1 were also elevated in HCDL individuals compared to HCNDL. Principal component analyses provided further evidence that lipid mediators could serve as an early biomarker for progression to active leprosy. A logistic model identified resolvin D1 and D2, and prostaglandin D2 as having the greatest potential for early detection of HCs that will manifest leprosy.

Gene Expression of Human Beta-Defensin-3 and Cathelicidin in the Skin of Leprosy Patients, Household Contacts, and Healthy Individuals from Indonesia.

Background: Leprosy, a chronic infectious peripheral neuropathy, is caused by Mycobacterium leprae. This bacterium produces triacylated lipopeptides that can induce the immune system via the Toll-like receptor 2/1 (TLR 2/1) complex. Activation of TLR 2/1 produces proinflammatory cytokines and antimicrobial peptides (AMPs), including human beta-defensin-3 (HBD-3) and cathelicidin. Purpose: To analyze differences in gene expression of HBD-3 and cathelicidin in the skin of leprosy patients, household contacts, and healthy individuals. Patients and Methods: An analytic observational study was conducted at the Outpatient Clinic of Dermatology and Venereology of Dr Mohammad Hoesin General Hospital, Palembang, Indonesia, from January 2021 to June 2022. In each group of 18 subjects, 72 samples were collected, including skin lesion in leprosy patients, normal skin in leprosy patients, household contacts, and healthy individuals. A comparison of HBD-3 and cathelicidin gene expression between the four groups was analyzed using Pearson Chi Square, Kruskal-Wallis, and Mann-Whitney Test. Results: The median value of HBD-3 gene expression on skin lesion in leprosy patients was 260.61 (0.19-3734.10); normal skin in leprosy patients was 1.91 (0.01-151.17); household contacts skin was 7.93 (0.27-121.10); and healthy individuals' skin was 1.00 (1.00-1.00) is highly significant difference (p < 0.0001). The median value of cathelicidin gene expression on skin lesion in leprosy patients was 38.72 (0.28-1852.17); normal skin in leprosy patients was 0.48 (0.01-15.83); household contacts skin was 9.8 (0.04-128.0); and healthy individual skin was 1.00 (1.00-1.00), also highly significant difference (p < 0.0001). Conclusion: Gene expression of HBD-3 and cathelicidin increased in skin lesions of leprosy patients and household contacts.

1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis.

BACKGROUND: Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups. METHODS: We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year. Incidence was estimated across age and risk groups (<5 years; ≥5 years, diagnosed with human immunodeficiency virus [HIV]; ≥5 years, not diagnosed with HIV/unknown, baseline TBI-positive) by logistic or log-binomial regression fitted using generalized estimating equations. RESULTS: Of 1016 HHCs, 850 (83.7%) from 247 households were assessed (median, 51.4 weeks). Among 242 HHCs, 52 tested interferon-gamma release assay-positive, yielding a 1-year 21.6% (95% confidence interval [CI], 16.7-27.4) TBI cumulative incidence. Sixteen of 742 HHCs developed confirmed (n = 5), probable (n = 3), or possible (n = 8) TBD, yielding a 2.3% (95% CI, 1.4-3.8) 1-year cumulative incidence (1.1%; 95% CI, .5-2.2 for confirmed/probable TBD). TBD relative risk was 11.5-fold (95% CI, 1.7-78.7), 10.4-fold (95% CI, 2.4-45.6), and 2.9-fold (95% CI, .5-17.8) higher in age <5 years, diagnosed with HIV, and baseline TBI high-risk groups, respectively, vs the not high-risk group (P = .0015). By 1 year, 4% (21 of 553) of high-risk HHCs had received TPT. CONCLUSIONS: TBI and TBD incidence continued through 1 year in rifampin-/multidrug-resistant TB HHCs. Low TPT coverage emphasizes the need for evidence-based prevention and scale-up, particularly among high-risk groups.