Comprehension of Calcitriol Levels in Pregnant Women With Latent Tuberculosis and Immune Function in their Newborns.

Background: Pregnant women with latent tuberculosis infection (LTBI) may develop active tuberculosis infection and could infect their neonates, which could impair the child's immune system due to infection-mediated immunological responses. In order to develop a preventative TB program in this study, we desired to understand the impact of calcitriol in LTBI pregnant women and immunological responses in neonates. Patients and Methods: In three hospitals in Medan, North Sumatra, we implemented a case-control design with 84 pregnant women in their third trimester and their newborns. We determined the levels of calcitriol, cathelicidin, and interferon gamma (IFN-γ) in women between December 2021 and July 2022. These measurements were then compared to the newborns' levels of calcitriol, cathelicidin, IFN-γ, and Toll-Like Receptor (TLR) 2. Analyses were performed using the Chi-squared and Fisher's tests, while Spearman correlations were employed to assess for correlations. Results: 42 pregnant women with LTBI (interferon gamma release assay (IGRA) positive) and 42 pregnant women without LTBI (IGRA negative) participated in the study. The findings demonstrated that pregnant women with LTBI were at increased risk for calcitriol deficiency (Odds Ratio (OR) = 3.667, p = 0.006), which had an impact on the calcitriol levels of their unborn children (p = 0.038). TLR2 levels and calcitriol levels were substantially associated with LTBI pregnant women and their healthy neonates (p = 0.048; p = 0.005). Cathelicidin levels in the newborns of non-LTBI pregnant women were influenced by their higher calcitriol levels (p = 0.043). Pregnant women with LTBI had higher levels of cathelicidin and IFN-γ than those without it (p = 0.03; p = 0.001). Conclusion: Pregnant LTBI women's calcitriol levels had an impact on the calcitriol levels of their newborns. Mother's immunological responses and babies' calcitriol levels affected the levels of cathelicidin, IFN-γ, and TLR2 in newborns.

Stigma, depression, quality of life, and the need for psychosocial support among people with tuberculosis in Indonesia: A multi-site cross-sectional study.

Stigma towards people with tuberculosis (TB-Stigma) is associated with other psychosocial consequences of TB including mental illness and reduced quality of life (QoL). We evaluated TB-Stigma, depression, QoL, and the need for psychosocial support among adults with TB in Indonesia, a high TB burden country. In this primary health facility-based survey in seven provinces of Indonesia, from February to November 2022, we interviewed adults receiving (a) intensive phase treatment for drug-susceptible (DS) TB at public facilities, (b) treatment at private facilities, (c) those lost to follow up (LTFU) to treatment, and (d) those receiving TB retreatment. We used our previously validated Indonesian TB-Stigma Scale, Patient Health Questionnaire-9, and EQ-5D-5L to measure TB-Stigma, depression, and QoL. Additional questions assessed what psychosocial support was received or needed by participants. We recruited and interviewed 612 people, of whom 60.6% (96%CI 59.6-64.5%) experienced moderate TB-Stigma. The average TB-Stigma scores were 19.0 (SD 6.9; min-max 0-50; Form A-Patient Perspective) and 23.4 (SD 8.4, min-max 0-50; Form B-Community Perspective). The scores were higher among people receiving treatment at private facilities (adjusted B [aB] 2.48; 0.94-4.03), those LTFU (aB 2.86; 0.85-4.87), males (aB 1.73; 0.59-2.87), those losing or changing job due to TB (aB 2.09; 0.31-3.88) and those living in a rural area (aB 1.41; 0.19-2.63). Depression was identified in 41.5% (95% CI 37.7-45.3%) of participants. Experiencing TB-Stigma was associated with moderately severe to severe depression (adjusted odds ratio [aOR] 1.23; 1.15-1.32) and both stigma and depression were associated with lower QoL (aB -0.013; [-0.016]-[-0.010]). Informational (20.8%), emotional (25.9%) and instrumental (10.6%) support received from peers or peer-groups was limited, and unmet need for such support was high. There is a sizeable and intersecting burden of TB-Stigma and depression among adults with TB in Indonesia, which is associated with lower QoL. Participants reported a substantial unmet need for psychosocial support including peer-led mutual support groups. A community-based peer-led psychosocial support intervention is critical to defray the psychosocial impact of TB in Indonesia.

Nasopharyngeal carriage and antimicrobial susceptibility profiles of Streptococcus pneumoniae among children with pneumonia and healthy children in Padang, Indonesia.

Streptococcus pneumoniae is one of the pathogenic bacteria causing invasive pneumococcal diseases such as pneumonia, sepsis, and meningitis, which are commonly reported in children and adults. In this study, we investigated the nasopharyngeal carriage rates, serotype distribution, and antimicrobial susceptibility profiles of S. pneumoniae among children with pneumonia and healthy children under 5 years old in Padang, West Sumatra, Indonesia. Nasopharyngeal swabs were collected from 65 hospitalized children with pneumonia in a referral hospital and from 65 healthy children at two day-care centers from 2018 to 2019. S. pneumoniae was identified by conventional and molecular methods. Antibiotic susceptibility was performed with the disc diffusion method. Out of 130 children, S. pneumoniae strains were carried by 53% and 9.2 % in healthy children (35/65) and children with pneumonia (6/65), respectively. Serotype 19F was the most common serotype among the isolated strains (21%) followed by 6C (10%), 14, 34 (7 % each), and 1, 23F, 6A, 6B (5 % each). Moreover, 55 % of the strains (23/42) were covered by the 13-valent pneumococcal conjugate vaccine. Most isolates were susceptible to vancomycin (100%), chloramphenicol (93%), clindamycin (76%), erythromycin (71%), and tetracycline (69%). Serotype 19F was commonly found as a multi-drug resistant strain.

Stigma towards people with tuberculosis: a cross-cultural adaptation and validation of a scale in Indonesia.

INTRODUCTION: Tuberculosis (TB) remains a highly stigmatised disease that can cause or exacerbate mental health disorders. Despite increased awareness of the importance of reducing TB stigma, validated tools to measure TB stigma remain scarce. This study aimed to culturally adapt and validate the Van Rie TB Stigma Scale in Indonesia, a country with the second largest TB incidence worldwide. METHODS: We validated the scale in three phases: translation, cultural adaptation, and psychometric evaluation. We invited diverse experts to an interdisciplinary panel for the cross-cultural adaptation, then performed a psychometric evaluation of the scale: exploratory and confirmatory factor analyses, reliability analysis, and correlation analysis with Patient Health Questionnaire 9 [PHQ-9]. RESULTS: We culturally adapted the original scale's language and content during the translation and cultural adaptation phases. After psychometric evaluation with 401 participants in seven provinces of Indonesia, we removed two items. The new scale had two forms: (A) patient and (B) community perspective forms. Both forms had good internal consistency, with respective Cronbach's alpha values of 0.738 and 0.807. We identified three loading factors in Form A (disclosure, isolation, and guilty) and two loading factors in Form B (isolation and distancing). The scale showed correlation with PHQ-9 (Form A, rs = 0.347, p < 0.001; Form B, rs = 0). CONCLUSIONS: The culturally adapted Indonesian version of Van Rie's TB Stigma Scale is comprehensive, reliable, internally consistent, and valid. The scale is now ready for applied scale-up in research and practice to measure TB-stigma and evaluate the impact of TB-stigma reduction interventions in Indonesia.

The development of the national tuberculosis research priority in Indonesia: A comprehensive mixed-method approach.

Ranked second in global tuberculosis (TB) incidence, Indonesia has developed a National Strategy for TB Prevention and Control 2020-2024 to accelerate the TB elimination program. Research and innovation are key pillars to support the program and need to be prioritised. This study aimed to develop updated national TB research priorities in Indonesia. This study was a mixed-methods study consisting of an open survey, a published literature survey, and Delphi survey. The open survey invited all related TB stakeholders to answer (a) the main barriers of the TB program and (b) the need for studies to support TB elimination. The published literature survey retrieved scientific articles published in national and international journals between 2015 and 2020 to identify gaps between published research and the current national strategy for TB control. The online survey and literature survey informed a panel of TB experts in a two-phase Delphi Survey to select the top 10 priority research topics. We identified 322 articles and analysed 1143 open survey responses. Through two-phases Delphi surveys, top ten research categories were listed: early TB detection; diagnosis and treatment of DR-TB; contact investigation; case detection and treatment of child TB; TB preventive therapy; government policy; laboratory for drug-sensitive- and drug-resistant-TB diagnosis; treatment adherence; diagnostic tool development; and community empowerment. This study also found the gap between stakeholders' interests and the importance of translating research into policy and practice. TB research priorities have been identified through the involvement of various stakeholders. The combination of an online survey, a published literature survey, and a Delphi survey was a rigorous methodology and was fit to build a systematic consensus about the priority of TB research.

Missing Cases of Bacteriologically Confirmed TB/DR-TB from the National Treatment Registers in West and North Sumatra Provinces, Indonesia.

This study aimed to assess the percentage of confirmed drug-sensitive (DS) TB and drug-resistant (DR) TB patients who were missing in the national treatment registration in North Sumatra and West Sumatra, where treatment services for DR-TB in North Sumatra are relatively well established compared with West Sumatra, where the system recently started. Confirmed DS/DR-TB records in the laboratory register at 40 government health facilities in 2017 and 2018 were traced to determine whether they were in the treatment register databases. A Jaro-Winkler soundexed string distance analysis enhanced by socio-demographic information matching had sensitivity and specificity over 98% in identifying the same person in the same or different databases. The laboratory data contained 5885 newly diagnosed records of bacteriologically confirmed TB cases. Of the 5885 cases, 1424 of 5353 (26.6%) DS-TB cases and 133 of 532 (25.0%) DR-TB cases were missing in the treatment notification database. The odds of missing treatment for DS-TB was similar for both provinces (AOR = 1.0 (0.9, 1.2), but for DR-TB, North Sumatra had a significantly lower missing odds ratio (AOR = 0.4 (0.2, 0.7). The system must be improved to reduce this missing rate, especially for DR-TB in West Sumatra.

Characterising and Addressing the Psychosocial Impact of Tuberculosis in Indonesia (CAPITA): A study protocol.

Background: Tuberculosis (TB)-related stigma remains a key barrier for people with TB to access and engage with TB services and can contribute to the development of mental illnesses. This study aims to characterise stigmatisation towards people with TB and its psychosocial impact in Indonesia. Methods: This study will apply a sequential mixed method in two main settings: TB services-based population (setting 1) and workplace-based population (setting 2). In setting 1, we will interview 770 adults with TB who undergo sensitive-drug TB treatment in seven provinces of Indonesia. The interview will use the validated TB Stigma Scale questionnaire, Patient Health Questionnaire-9, and EQ-5D-5L to assess stigma, mental illness, and quality of life. In Setting 2, we will deploy an online questionnaire to 640 adult employees in 12 public and private companies. The quantitative data will be followed by in-depth interview to TB-related stakeholders. Results: CAPITA will not only characterise the enacted stigma which are directly experienced by people with TB, but also self-stigma felt by people with TB, secondary stigma faced by their family members, and structural stigma related to the law and policy. The qualitative analyses will strengthen the quantitative findings to formulate the potential policy direction for zero TB stigma in health service facilities and workplaces. Involving all stakeholders, i.e., people with TB, healthcare workers, National Tuberculosis Program officers, The Ministry of Health Workforce, company managers, and employees, will enhance the policy formulation. The validated tool to measure TB-related stigma will also be promoted for scaling up to be implemented at the national level. Conclusions: To improve patient-centered TB control strategy policy, it is essential to characterise and address TB-related stigma and mental illness and explore the needs for psychosocial support for an effective intervention to mitigate the psychosocial impact of TB.

Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Indonesian children: A cross-sectional study.

Streptococcus pneumoniae is an important cause of infection and commonly colonizes the nasopharynx of young children, along with other potentially pathogenic bacteria. The objectives of this study were to estimate the carriage prevalence of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in young children in Indonesia, and to examine interactions between these bacterial species. 302 healthy children aged 12-24 months were enrolled in community health centers in the Bandung, Central Lombok, and Padang regions. Nasopharyngeal swabs were collected and stored according to World Health Organization recommendations, and bacterial species detected by qPCR. Pneumococcal serotyping was conducted by microarray and latex agglutination/Quellung. Overall carriage prevalence was 49.5% for S. pneumoniae, 27.5% for H. influenzae, 42.7% for M. catarrhalis, and 7.3% for S. aureus. Prevalence of M. catarrhalis and S. pneumoniae, as well as pneumococcal serotype distribution, varied by region. Positive associations were observed for S. pneumoniae and M. catarrhalis (OR 3.07 [95%CI 1.91-4.94]), and H. influenzae and M. catarrhalis (OR 2.34 [95%CI 1.40-3.91]), and a negative association was found between M. catarrhalis and S. aureus (OR 0.06 [95%CI 0.01-0.43]). Densities of S. pneumoniae, H. influenzae, and M. catarrhalis were positively correlated when two of these species were present. Prior to pneumococcal vaccine introduction, pneumococcal carriage prevalence and serotype distribution varies among children living in different regions of Indonesia. Positive associations in both carriage and density identified among S. pneumoniae, H. influenzae, and M. catarrhalis suggest a synergistic relationship among these species with potential clinical implications.

Risk factors associated with nasopharyngeal carriage and density of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in young children living in Indonesia.

BACKGROUND: Potentially pathogenic bacteria Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus are commonly carried in the nasopharynx of young children. Host and environmental factors have been linked with pathogen carriage, and in many studies rural children have higher carriage rates than their urban counterparts. There are few published data on what factors contribute to increased pathogen density. The objectives of this study were to identify risk factors for nasopharyngeal carriage and density of S. pneumoniae, H. influenzae, M. catarrhalis, and S. aureus in young children in Indonesia. METHODS: Risk factor analysis was done using data on bacterial carriage and participant characteristics from a cross-sectional study that enrolled 302 children aged 12-24 months living in urban or semi-rural areas of Indonesia. Associations between host factors and odds of pathogen carriage were explored using logistic regression. Characteristics identified to be independent predictors of carriage by univariable analysis, as well as those that differed between urban and semi-rural participants, were included in multivariable models. Risk factors for increased pathogen density were identified using linear regression analysis. RESULTS: No differences in carriage prevalence between urban and semi-rural children were observed. Multiple children under the age of 5 years in the household (< 5y) and upper respiratory tract infection (URTI) symptoms were associated with S. pneumoniae carriage, with adjusted odds ratios (aOR) of 2.17 (95% CI 1.13, 4.12) and 2.28 (95% CI 1.15, 4.50), respectively. There was some evidence that URTI symptoms (aOR 1.94 [95% CI 1.00, 3.75]) were associated with carriage of M. catarrhalis. Children with URTI symptoms (p = 0.002), and low parental income (p = 0.011) had higher S. pneumoniae density, whereas older age was associated with lower S. pneumoniae density (p = 0.009). URTI symptoms were also associated with higher M. catarrahlis density (p = 0.035). Low maternal education (p = 0.039) and multiple children < 5y (p = 0.021) were positively associated with H. influenzae density, and semi-rural residence was associated with higher S. aureus density (p < 0.001). CONCLUSIONS: This study provides a detailed assessment of risk factors associated with carriage of clinically-relevant bacteria in Indonesian children, and new data on host factors associated with pathogen density.

Vitamin D status in under-five children with a history of close tuberculosis contact in Padang, West Sumatra.

BACKGROUND AND OBJECTIVE: Serum vitamin D influences cellular immunity against Mycobacterium tuberculosis, particularly in under-five children. Vitamin D insufficiency and deficiency as well as tuberculosis (TB) are highly prevalent in Indonesia. This study described the association of serum vitamin D in the incidence of latent TB in under-five children with a history of close TB contact. METHODS AND STUDY DESIGN: This cross-sectional study examined 178 under-five children with a history of close TB contact, with 98 index cases from primary health care facilities in Padang. Latent TB was defined based on a positive tuberculin skin test. Serum vitamin D was determined using ELISA method. General characteristics for age, sex, socioeconomic status, contact score, BCG scars, and nutritional status were also collected. RESULTS: Of 168 eligible subjects, 40.5% had latent TB, however no differences between 'latent TB' and 'without latent TB' were observed in participant characteristics. Vitamin D deficiency, insufficiency, and sufficiency were observed in 23.3%, 43.5%, and 33.3% of children, respectively. In general, the 'latent TB' group had lower serum vitamin D than those in the 'without latent TB' group, stratified by age, contact score and nutritional status; however, significant differences were observed in children age <1 years (18.0±2.6 vs 31.2±10.5, respectively, p=0.013). Nevertheless, no associations between the two groups were observed using multivariate analysis. CONCLUSION: Vitamin D status was not associated with the incidence of latent TB among under-five children with a history of close TB contact, although this may not obtain in children aged <1 year old.