High TB Burden Countries Research Articles

Adverse events reported during weekly isoniazid-rifapentine (3HP) tuberculosis preventive treatment among people living with HIV in Uganda.

Short-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AE) could differ in routine settings. Real-world data on AE type, frequency, and timing is crucial for health systems considering 3HP programmatic scale-up. We reviewed AEs among people living with HIV (PLHIV) participating in a pragmatic implementation trial of facilitated 3HP taken by directly observed therapy (DOT) or self-administered therapy (SAT) in Kampala, Uganda, and classified them using the Common Terminology Criteria for Adverse Events. We assessed AE timing and summarized related clinical actions including lab tests, diagnoses made, medications prescribed, and treatment interruptions. Among 1655 PLHIV treated between July 2020-September 2022, 270 (16.3%) reported 451 events; main issues included general (7%), nervous system (6%), musculoskeletal (5%), gastrointestinal (5%), and dermatologic (3%) disorders. Most (61%) occurred within 6 weeks of initiating 3HP. Among those with events, 211 (78%) required further clinician evaluation, 202 (75%) required laboratory testing, 102 (38%) had medications prescribed, 40 (15%) had treatment paused, and 14 (5%) discontinued 3HP. Women, those multidimensionally impoverished, and DOT recipients were more likely to report an AE. SAT users and later enrollees were more likely to have 3HP interrupted or stopped due to an AE. In a routine setting, 3HP was safe with 16% of PLHIV reporting AEs and only 3% requiring temporary or permanent treatment interruption. These findings support 3HP expansion in routine HIV/AIDS care settings for TB prevention.

NAVIGATING BARRIERS: THE NEED FOR INTEGRATED HEALTH INFORMATION SYSTEM FOR TUBERCULOSIS-DIABETES CO-SCREENING

Background: Tuberculosis-diabetes mellitus (TB-DM) is a co-epidemic condition representing a double burden for high TB burden countries like Indonesia. Private primary care (PPC) in Indonesia was newly reintroduced to the TB program. Aims: This study explores the challenges PPC healthcare workers (HCWs) face in implementing TB-DM bi-directional screening and strategies to improve it. Methods: An explorative qualitative method was used by conducting two-round focus group discussions (FGDs) with HCWs (n=15) from five private clinics in Yogyakarta Special Region Province Indonesia and triangulated with 10 DM patients and the TB program manager from the provincial health office. The data were audio recorded, transcribed verbatim, and subjected to thematic analysis. Results: HCWs face complex barriers in TB-DM co-screening implementation from patients, HCWs, and health system aspects. An integrated system to remind, support decision-making, report, reduce documentation duplication, monitor, and evaluate co-screening implementation emerged as a potential strategy, although some challenges to deploy. Conclusion: Albeit HIS is promising in enhancing integrated TB-DM screening and management, a comprehensive approach and multisector roles are still needed to overcome impediments to TB-DM bidirectional screening in PPCs. Keywords: diabetes mellitus, health information system, screening, tuberculosis

Relationship between nutritional status and the incidence of tuberculosis transmission in the family in Batusumur Village, Manonjaya Subdistrict Tasikmalaya Regency

Tuberculosis is the second infectious disease that causes the most deaths in the world according to WHO. Indonesia is a high TB burden country which currently ranks third in the world, with an incidence of 845.000 or 320/100.000 population with a mortality rate of 98.000 or 40/100.000 population and 3,6/100.000 TB-HIV population. The risk factor that can cause tuberculosis disease is malnutrition. The aim of the study was to determine the relationship between nutritional status and the incidence of tuberculosis transmission in the family. The purpose of this study was to determine the relationship between nutritional status and the incidence of tuberculosis. The research design used cross sectional study. The research was conducted in December 2023 in Batusumur Village, Manonjaya District, Tasikmalaya Regency. The research sample was 39 respondents of tuberculosis patients. Inclusion criteria: patients actively communicate and are easy to talk to, patients live with family members and are still in the initial phase of treatment in the first 2 months. The independent variable was nutritional status. The dependent variable was the incidence of pulmonary tuberculosis transmission in family members. The instrument was an observation sheet. Data were analyzed by chi square test using SPSS. This research applies the principles of confidentiality, useful information and scientific development. The results showed that there was a relationship between nutritional status (p=0,026) and the incidence of tuberculosis transmission in the family. The conclusion is that there is a relationship between nutritional status and the incidence of tuberculosis. Tuberculosis patients and their families can make preventive efforts to prevent tuberculosis transmission.

TB and interstitial lung disease: a systematic review and meta-analysis.

<sec id="st1"><title>INTRODUCTION</title>To determine the frequency of TB among patients with interstitial lung diseases (ILDs).</sec><sec id="st2"><title>METHODS</title>We performed a comprehensive search in the PubMed/Medline, EMBASE and Scopus databases up to 1 August 2023 of studies reporting on the prevalence of TB among patients with ILDs.</sec><sec id="st3"><title>RESULTS</title>Twelve studies comprising 3,817 patients with ILD were found: the pooled prevalence of TB among ILD patients was 11.0% (95% CI 5.4-21.0). In the subgroup analysis, the TB rate among patients with silicosis and idiopathic pulmonary fibrosis (IPF) was respectively 35.6% (95% CI 32.6-38.8) and 4.4% (95% CI 3.6-5.3) (P = 0.00). The frequency of TB among ILD patients was higher in high TB burden countries than in low/intermediate-burden countries: 26.3%, 95% CI 17.7-37.3 vs. 4.9%, 95% CI 3.3-7.2; P = 0.00.</sec><sec id="st4"><title>CONCLUSIONS</title>This study shows the frequency of TB among ILD patients. The meta-analysis reveals a significantly increased prevalence of TB among ILD patients with silicosis compared to IPF, and among individuals in high TB burden countries than in those with low/intermediate burden. The study results can help physicians and policymakers make efficient decisions for prompt screening and anti-TB treatment initiation in ILD patients.</sec>.

Operational research as a mechanism to improve treatment outcomes for drug-resistant TB in the WHO European Region.

In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe. The aim was to introduce three, fully oral, 9-month modified shorter treatment regimens (mSTR) to treat RR/MDR-TB under operational research conditions. The three regimens were: 1) bedaquiline + linezolid + levofloxacin + clofazimine + cycloserine (BdqLzdLfxCfzCs); 2) BdqLzdLfxCfz + delamanid (Dlm) for children over 6 years of age and adults; and 3) DlmLzdLfxCfz for children under 6 years of age. The project aimed to enhance treatment success, facilitate mSTR implementation, promote quality of care and build research capacity, while also contributing to global knowledge on all-oral mSTR use. Between April 2020 and June 2022, >2,800 patients underwent mSTR treatment in the WHO European Region. This unique experience promoted further collaboration with national tuberculosis programmes, health authorities, experts and donors within and outside Europe, with a focus on implementing operational research and improving the quality of care in high TB burden countries of the region. In the hope of encouraging others to adopt this model, we have described the principles of the initiative, its strengths and weaknesses and next steps.

Risk factors for diagnosis and treatment delay among patients with multidrug-resistant tuberculosis in Hunan Province, China.

Multidrug-resistant tuberculosis (MDR-TB) is a global health threat associated with high morbidity and mortality rates. Diagnosis and treatment delays are associated with poor treatment outcomes in patients with MDR-TB. However, the risk factors associated with these delays are not robustly investigated, particularly in high TB burden countries such as China. Therefore, this study aimed to measure the length of diagnosis and treatment delays and identify their risk factors among patients with MDR-TB in Hunan province. A retrospective cohort study was conducted using MDR-TB data from Hunan province between 2013 and 2018. The main outcomes of the study were diagnosis and treatment delay, defined as more than 14days from the date of symptom to diagnosis confirmation (i.e., diagnosis delay) and from diagnosis to treatment commencement (i.e., treatment delay). A multivariable logistic regression model was fitted, and an adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to identify factors associated with diagnosis and treatment delay. In total, 1,248 MDR-TB patients were included in this study. The median length of diagnosis delays was 27days, and treatment delays were one day. The proportion of MDR-TB patients who experienced diagnosis and treatment delay was 62.82% (95% CI: 60.09-65.46) and 30.77% (95% CI: 28.27-33.39), respectively. The odds of experiencing MDR-TB diagnosis delay among patients coming through referral and tracing was reduced by 41% (AOR = 0.59, 95% CI: 0.45-0.76) relative to patients identified through consultations due to symptoms. The odds of experiencing diagnosis delay among ≥ 65years were 65% (AOR = 0.35, 0.14-0.91) lower than under-15 children. The odds of developing treatment delay among foreign nationalities and people from other provinces were double(AOR = 2.00, 95% CI: 1.31-3.06)compared to the local populations. Similarly, the odds of experiencing treatment delay among severely ill patients were nearly 2.5 timeshigher (AOR = 2.49, 95% CI: 1.41-4.42)compared to patients who were not severely ill.On the other hand, previously treated TB cases had nearly 40% (AOR = 0.59, 95% CI: 0.42-0.85) lower odds of developing treatment delay compared with new MDR-TB cases. Similarly, other ethnic minority groups had nearly 40% (AOR = 0.57, 95% CI: 0.34-0.96) lower odds of experiencing treatment delay than the Han majority. Many MDR-TB patients experience long diagnosis and treatment delays in Hunan province. Strengthening active case detection can significantly reduce diagnosis delays among MDR-TB patients. Moreover, giving attention to patients who are new to MDR-TB treatment, are severely ill, or are from areas outside Hunan province will potentially reduce the burden of treatment delay among MDR-TB patients.

CHILDHOOD TUBERCULOSIS: STUDY OF CLINICAL PROFILE OF TUBERCULOSIS IN PEDIATRIC PATIENTS AND CORRELATION OF CB-NAAT RESULT IN CLINICALLY SUSPECTED TUBERCULOSIS

Introduction: Tuberculosis is a chronic infectious disease caused by predominantly Mycobacterium tubercle bacilli. Pediatric tuberculosis is among the top 10 causes of death in children. India accounts for one fourth of the global tuberculosis burden, standing one among the thirty high TB burden countries. Hence, children in India are at increased risk of acquiring TB infection and developing TB disease and death following infection. Latent TB infection in children may be reactivated in later life and become active adulthood tuberculosis and thereby a potent TB reservoir in the community. Aim: To study clinical profile of tuberculosis in pediatric patients and correlation of CB-NAAT result in clinically suspected tuberculosisat tertiary care center. Method: Prospective Observational study from1 August 2020 to 31 August 2022. Result: Out of 52 patients cough was presenting symptom of 19(36.53%), fever was present in 25(48.07%), loss of weight &gt;5% in last 3 month was present in 12(23.07%),fever(83.8 %) was most dominant symptom. Out of 52 patients, tachypnoea was presenting sign in 5(9.6%), ascites was present in 5(9.6%) and lymphadenopathy for more than 2 weeks were present in 25(48.07%). Out of 52 patients Anaemia was present in 42(80.76%), High ESR was present in 22(42.30%) and Mantoux test was positive in 16(30.76%). Conclusion: Reliable diagnosis of tuberculosiscan be done by clinical parameters like presence of tachypnea, fever and lymphadenopathy. CB NAAT in correlation to clinical parameters is very useful for diagnosis of tubercular cases.

Xpert MTB/RIF Ultra for the rapid diagnosis of extrapulmonary tuberculosis in a clinical setting of high tuberculosis prevalence country and interpretation of ‘trace’ results

To evaluate the diagnostic performance of Xpert MTB/RIF Ultra (Ultra) for the diagnosis of extrapulmonary tuberculosis (EPTB) from different types of extrapulmonary specimens in comparison with culture and composite microbiological reference standard (CRS). A total of 240 specimens were prospectively collected from presumptive EPTB patients between July 2021–January 2022 and tested by Ultra, Xpert, culture and acid-fast bacilli (AFB) smear microscopy. Out of 240 specimens, 35.8 %, 20.8 %, 11.3 %, and 7.1 % were detected as Mycobacterium tuberculosis complex by Ultra, Xpert, culture and AFB microscopy, respectively. An additional 15.0 % cases were detected by Ultra compared to Xpert MTB/RIF (Xpert) assay. A total of 28 (11.7 %) cases were identified as ‘trace’ category by Ultra with indeterminate rifampicin resistance result; of which 36.4 % were clinically confirmed as EPTB. Compared to culture, the sensitivity and specificity of Ultra and Xpert were 100 % and 72.3 %; 92.6 % and 88.3 %, respectively. In comparison with CRS, these were respectively: 98.9 % and 100 %; 57.5 % and 100 %. For individual category of specimens, sensitivity of Ultra was 100 % with varying specificity. We found that Ultra was highly sensitive for the rapid diagnosis of EPTB and has extensive potential over current diagnostics in high TB burden countries, but ‘trace’ results should be interpreted with caution.

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.

Disseminated Tuberculosis: A 6-year Case Series Experience in a Tertiary Care Center.

Disseminated tuberculosis (dTB) disease is associated with a significant burden of morbidity and mortality and it requires improved awareness among clinicians. Case reports revealing the clinical and microbiological characteristics of dTB patients will help us to extend our knowledge of dTB. In our study, we have documented dTB cases followed for 6 years and revealed patients' clinical characteristics. Patients followed between 2017 and 2023 who were diagnosed with dTB in a tertiary referral hospital in Istanbul have been evaluated. Data regarding patients' characteristics, methods used in establishing the definitive diagnosis, radiological patterns in chest X-rays, extrapulmonary sites involved, antituberculosis (TB) treatment regimens received, medication side effects, and drug resistance have been examined. Descriptive statistics were performed. Clinical characteristics of 55 patients with a median age of 41 (range 20-85, 52.7% male) were examined. The most common extrapulmonary involvements in our study were the skeletal system (n = 24), central nervous system (n = 7), and genitourinary tract (n = 7). Isoniazid (INH) resistance was detected in four patients. Mono resistance was reported for pyrazinamide in one patient. Multidrug resistance was detected in two patients and one of them was also resistant to ethambutol. Preextensively, drug resistance was reported in three patients. Another three patients were evaluated as resistant to both INH and streptomycin. Migrating from a high TB burden country and comorbidities such as diabetes mellitus, human immunodeficiency virus, and rheumatoid arthritis that are related to immunocompromisation are thought to be risk factors for dTB.

Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

Non-Tuberculous Mycobacteria Infections based on 16S rRNA detections in patients with Suspected Chronic Tuberculosis at a Tertiary Referral Hospital in Indonesia

This study identified non-tuberculous mycobacteria (NTM) isolates from the clinical respiratory specimen of patients suspected of chronic tuberculosis at a tertiary referral hospital in Indonesia. In this study, 20 clinical non-tuberculous mycobacteria (NTM) isolates were obtained from respiratory samples examined in the tuberculosis section of the Clinical Microbiology laboratory at Dr Soetomo General Hospital. The isolates were identified using TB Ag MPT 64 (SD Bioline) and targeting 16S rRNA genes sequence for analysis at the species level. Data on clinical features were collected and chest radiographs were evaluated. The highest bacterium found in the isolates was Mycobacterium kansasii (12 strains, 60%.), followed by Mycobacterium gordonae (2 strains, 5%), Mycobacterium parascofulaceum (2 strains, 5%), Mycobacterium avium (1 strain, 2.5%), Mycobacterium simiae (1 strain, 2.5%). Mycobacterium abcessus (1 strain, 2.5%), and Mycobacterium paraterrae (1 strain, 2.5%). Males dominated patients with Mycobacterium kansasii. Clinical symptoms include cough, dyspneu, hemoptysis, chest pain, and sweats. Half of the patients had a history of previous tuberculosis and other comorbid diabetes mellitus. Non-tuberculous mycobacteria (NTM) species identified were dominated by Mycobacterium kansasii. The predominance of non-tuberculous mycobacteria (NTM) species from clinical respiratory can be a reference to determine prudent treatment for patients in high-burden TB countries.

Lessons for TB from the COVID-19 response: qualitative data from Brazil, India and South Africa

BACKGROUND: Brazil, India and South Africa are among the top 30 high TB burden countries globally and experienced high rates of SARS-CoV-2 infection and mortality. The COVID-19 response in each country was unprecedented and complex, informed by distinct political, economic, social and health systems contexts. While COVID-19 responses have set back TB control efforts, they also hold lessons to inform future TB programming and services.METHODS: This was a qualitative exploratory study involving interviews with TB stakeholders (n = 76) in Brazil, India and South Africa 2 years into the COVID-19 pandemic. Interview transcripts were analysed using an inductive coding strategy.RESULTS: Political will – whether national or subnational – enabled implementation of widespread prevention measures during the COVID-19 response in each country and stimulated mobile and telehealth service delivery innovations. Participants in all three countries emphasised the importance of mobilising and engaging communities in public health responses and noted limited health education and information as barriers to implementing TB control efforts at the community level.CONCLUSIONS: Building political will and social mobilisation must become more central to TB programming. COVID-19 has shown this is possible. A similar level of investment and collaborative effort, if not greater, as that seen during the COVID-19 pandemic is needed for TB through multi-sectoral partnerships.

The Role of GeneXpert® for Tuberculosis Diagnostics in Brazil: An Examination from a Historical and Epidemiological Perspective.

The rapid molecular test (RMT) performed on the GeneXpert® system is widely used as a control strategy and surveillance technique for tuberculosis (TB). In the region of the Americas, TB incidence is slowly increasing owing to an upward trend in Brazil, which is among the high TB-burden countries (HBCs), ranking in the 19th position. In this context, we aimed to (i) describe the implementation and history of RMT-TB (Xpert® MTB/RIF and Xpert® MTB/RIF Ultra) in Brazil; (ii) to evaluate the national RMT laboratory distribution, TB, and resistance to RIF detection by RMT; and (iii) to correlate these data with Brazilian TB incidence. The quantitative data of Xpert® MTB/RIF and Xpert® MTB/RIF Ultra assays performed in the pulmonary TB investigation from 2014 to 2020 were provided by the Brazilian Ministry of Health. A spatial visualization using ArcGIS software was performed. The Southeast region constituted about half of the RMT laboratories-from 39.4% to 45.9% of the total value over the five regions. Regarding the federal units, the São Paulo state alone represented from 20.2% to 34.1% (5.0 to 8.5 times the value) of RMT laboratories over the years observed. There were significant differences (p < 0.0001) in the frequency of RMT laboratories between all years of the historical series. There was an unequal distribution of RMT laboratories between Brazilian regions and federal units. This alerts us for the surveillance of rapid molecular detection of TB in different parts of the country, with the possibility of improving the distribution of tests in areas of higher incidence in order to achieve the level of disease control recommended by national and worldwide authorities.

Mycobacterium tuberculosis epidemiology in Oman: whole-genome sequencing uncovers transmission pathways.

Tuberculosis (TB) originating from expatriates that hail from high TB-burden countries is hypothesized to play a role in continued TB transmission in Oman. Here, we used whole-genome sequencing (WGS) to assess national TB transmission dynamics. The annual incidence per 100,000 population per year was calculated for nationals and expatriates. A convenience sample of Mycobacterium tuberculosis (MTB) isolates from 2018 to 2019 was sequenced and analyzed with publicly available TB sequences from Bangladesh, Tanzania, the Philippines, India, and Pakistan. Relatedness was assessed by generating core-genome single nucleotide polymorphism (SNP) distances. The incidence of TB was five cases per 100,000 persons in 2018 and seven cases per 100,000 persons in 2020 (R2 = 0.34, P = 0.60). Incidence among nationals was 3.9 per 100,000 persons in 2018 and 3.5 per 100,000 persons in 2020 (R2 = 0.20, P = 0.70), and incidence among expatriates was 7.2 per 100,000 persons in 2018 and 12.7 per 100,000 persons in 2020 (R2 = 0.74, P = 0.34). Sixty-eight local MTB isolates were sequenced and analyzed with 393 global isolates. Isolates belonged to nine distinct spoligotypes. Two isolates, originating from an expatriate and an Omani national, were grouped into a WGS-based cluster (SNP distance < 12), which was corroborated by an epidemiological investigation. Relatedness of local and global isolates (SNP distance < 100) was also seen. The relatedness between MTB strains in Oman and those in expatriate countries of origin can aid inform TB control policy. Our results provide evidence that WGS can complement epidemiological analysis to achieve the End TB strategy goal in Oman. IMPORTANCE Tuberculosis (TB) incidence in Oman remains above national program control targets. TB transmission originating from expatriates from high TB-burden countries has been hypothesized to play a role. We used whole-genome sequencing (WGS) to assess TB transmission dynamics between expatriates and Omani nationals to inform TB control efforts. Available Mycobacterium tuberculosis isolates from 2018 to 2019 underwent WGS and analysis with publicly available TB sequences from Bangladesh, the Philippines, India, and Pakistan to assess for genetic relatedness. Our analysis revealed evidence of previously unrecognized transmission between an expatriate and an Omani national, which was corroborated by epidemiological investigation. Analysis of local and global isolates revealed evidence of distant relatedness between local and global isolates. Our results provide evidence that WGS can complement classic public health surveillance to inform targeted interventions to achieve the End TB strategy goal in Oman.

Tuberculin skin testing and QuantiFERON™-TB Gold Plus positivity among household contacts in Vietnam.

TB infection (TBI) is diagnosed using the technique-dependent tuberculin skin test (TST) or costly, more accurate interferon-gamma release assays. The TST (⩾10 mm) threshold was indicated by previous research among household contacts in Vietnam, but routine implementation with a different tuberculin reagent showed unexpectedly low TST positivity. TST (⩾5 mm and ⩾10 mm) results were compared to QuantiFERON™-TB Gold Plus (QFT) results in household contacts during community campaigns in 2020 and 2021. This was a cross-sectional multi-center implementation study. Among 1,330 household contacts in 2020, we found a TBI prevalence of 38.6% (QFT), similar to TST ⩾5 mm (37.4%) and higher than TST ⩾10 mm (13.1%). QFT+/TST+ was higher for TST ⩾5 mm (20.7%) than TST ⩾10 mm (9.4%). QFT was not discordant with TST ⩾5 mm (McNemar's test = 0.6, P = 0.5) but was discordant with TST ⩾10 mm (McNemar's test = 263.9, P < 0.01). Older age and Southern region increased odds for positive TST ⩾5 mm and QFT with weaker associations for TST ⩾10 mm. Agreement and discordance were similar in 2021 for 1,158 household contacts. Tuberculin reagents affect TST positivity rates. High TB burden countries should monitor reliability of TBI diagnosis, including tuberculin potency, cold chain, and TST technique to optimize eligibility for TB preventive treatment.

Pragmatic cluster-randomized trial of home-based preventive treatment for TB in Ethiopia and South Africa (CHIP-TB)

BackgroundEach year, 1 million children develop TB resulting in over 200,000 child deaths. TB preventive treatment (TPT) is highly effective in preventing TB but remains poorly implemented for household child contacts. Home-based child contact management and TPT services may improve access to care. In this study, we aim to evaluate the effectiveness and cost-effectiveness of home-based contact management with TPT initiation in two TB high-burden African countries, Ethiopia and South Africa.MethodsThis pragmatic cluster randomized trial compares home-based versus facility-based care delivery models for contact management. Thirty-six clinics with decentralized TB services (18 in Ethiopia and 18 in South Africa) were randomized in a 1:1 ratio to conduct either home-based or facility-based contact management. The study will attempt to enroll all eligible close child contacts of infectious drug-sensitive TB index patients diagnosed and treated for TB by one of the study clinics. Child TB contact management, including contact tracing, child evaluation, and TPT initiation and follow-up, will take place in the child’s home for the intervention arm and at the clinic for the control arm. The primary outcome is the cluster-level ratio of the number of household child contacts less than 15 years of age in Ethiopia and less than 5 years of age in South Africa initiated on TPT per index patient, comparing the intervention to the control arm. Secondary outcomes include child contact identification and the TB prevention continuum of care. Other implementation outcomes include acceptability, feasibility, fidelity, cost, and cost-effectiveness of the intervention.DiscussionThis implementation research trial will determine whether home-based contact management identifies and initiates more household child contacts on TPT than facility-based contact management.Trial registrationNCT04369326. Registered on April 30, 2020.

Forecasting Incidence Prevalence of Tuberculosis in Azad Jammu &amp; Kashmir: A Five-Year Retrospective Study

Background: Tuberculosis is one of the critical public health issue in Pakistan, according to report of WHO (2018), it holds 5th place among the TB high burden countries and estimated to be on fourth position for MDR prevalence. Currently, Pakistan is sharing 61% of case burden of TB in EMRO region. Methods: Polynomial regression model was used to predict the tuberculosis incidence prevalence in AJ&amp;K for the year 2019. Estimation based on tuberculosis data (2014-2018) analyzed for the incidence prevalence of tuberculosis in AJ&amp;K for 2019. Results: Tuberculosis incidence prevalence for 2018 was obtained 118/100000. The actual data of 2018 reported shows that averagely incidence prevalence of TB remains 124/100000 with minor difference from the predicted value of 2018. The data analysis from 2014 to 2018; predicted that average 130/100000 cases will be reported in 2019. Conclusion: This shows that AJ&amp;K is far from the target (270/100000) recognized by WHO. If one TB case produces 10 cases in community annually, then in coming years, there will be adversity of TB cases in the AJ&amp;K. It is suggested to WHO to revise its target.

Multi-drug resistant and rifampin-resistant tuberculosis in transplant recipients.

Management of multidrug-resistant (MDR) and rifampin-resistant (RR) tuberculosis is challenging. Data on transplant recipients is limited. We reviewed published literature to examine treatment choices, outcomes, and adverse effects from MDR-TB/RR-TB treatment in transplant recipients. Multiple databases from inception to 12/2022 were reviewed using the keywords "drug-resistant TB" or "drug-resistant tuberculosis" or "multidrug-resistant TB" or "multidrug-resistant tuberculosis". MDR-TB was defined as resistance to isoniazid (H) and rifampin (R), and RR if resistant to rifampin alone. Cases without patient-level data and reports which did not describe treatment and/or outcomes for MDR-TB were excluded. A total of 12 patients (10 solid organ transplants and two hematopoietic cell transplants) were included. Of these, 11 were MDR-TB and one was RR-TB. Seven recipients were male. The median age was 41.5 (range 16-60) years. Pre-transplant evaluation for the majority (8/12, 66.7%) did not reveal a prior history of TB or TB treatment, but 9/12 were from TB intermediate or high-burden countries. Seven patients were initially treated with the quadruple first-line anti-TB regimen. Those who had early RR confirmation (5/12) via Xpert MTB/RIF assay were initiated on alternative therapies. Final regimens were individualized based on susceptibility profiles and tolerability. Adverse events were reported in seven recipients, including acute kidney injury (n = 3), cytopenias (n = 3), and jaundice (n = 2). Four recipients died, with two deaths attributable to TB. The remaining eight patients who survived had functioning allografts at the last follow-up. MDR-TB treatment in transplant recipients is associated with many complications. Xpert MTB/RIF detected RR early and guided early empiric therapy.

Tuberculosis in migrants: epidemiology, resistance and outcome in Milan, Italy

Background Human migration and the ever-changing geopolitical scenarios are redefining the epidemiology and the management of tuberculosis (TB), especially in low-TB burden countries welcoming high rates of people from high-TB burden countries. Methods We conducted an observational retrospective mono-centric study in a Northern-Italy TB reference centre from 1 January 1990 to 31 December 2019, focusing on the differences in epidemiology, resistance patterns and treatment outcomes between Italians and migrants with active TB. Data were collected from medical records. Results A total of 10555 patients were included, 4614 Italians and 5941 migrants. Among migrants, higher rates of rifampin-resistant (RR) or multidrug-resistant (MDR) TB were reported, as well as higher rates of loss to follow-up. Among Italians, higher mortality rates and a higher number of extrapulmonary TB cases were found. Conclusion Our study describes one of the largest cohorts of patients with active TB in Italy, highlighting the need for tailored approaches in native and migrant populations.