High Tuberculosis Burden Countries Research Articles

Tuberculosis impacts multiple aspects in quality of life in a Romanian cohort of drug-susceptible and drug resistant patients: A patient-reported outcome measures study.

Tuberculosis (TB), and especially its drug resistant forms, is responsible for not only significant mortality, but also considerable morbidity, still under-quantified. This study used four Patient-Reported Outcome Measures (PROMS) to assess the status of persons affected by drug-susceptible and drug-resistant TB during their TB treatment or after treatment completion, in Romania, the highest TB burden country in the EU. People affected by TB in two different regions in Romania were included during and after treatment, following a cross-sectional design. PROMs used were SF-36, EQ-5D-5L, WPAI and the app-based audiometry screening tool 'uHear.' Descriptive statistics and relevant statistical tests were used to compare groups between themselves and with the general Romanian population. Both patients with drug-susceptible and drug-resistant TB experience, with drug-resistant patients experiencing statistically significantly more pain and hearing loss. PROMs show some improvement in the after-treatment group; however, compared with the general Romanian population for which data were available, all groups scored lower on all outcome measures. PROMs offer the possibility of obtaining a more comprehensive view of patients' status, by involving them directly in the medical process and could guide a rehabilitation strategy.

Undernutrition increases the risk of unsuccessful treatment outcomes of patients with tuberculosis in Ethiopia: A multicenter retrospective cohort study

While undernutrition has been identified as a common risk factor for tuberculosis (TB), its impact on treatment outcomes has yet to be investigated in high TB burden and low-income countries such as Ethiopia. Therefore, this study aimed to investigate the effect of undernutrition on treatment outcomes among patients with TB in northwest Ethiopia. A retrospective cohort study was conducted using data from different hospitals in northwest Ethiopia, for the period from July 2017 to August 2023. A Cox proportional hazard model was performed to determine the effect of undernutrition on TB treatment outcomes, which were defined as a composite of death, treatment failure, or loss to follow-up. A total of 602 patients with TB were included in the analysis. Of these, 367 (60.9%) were male, and 344 (57.1%) were undernourished. Upon completion of the follow-up period, 65 (10.8%) adults with TB had unsuccessful treatment outcomes. After adjusting for potential confounders, patients with undernutrition had a two times higher risk of experiencing unsuccessful treatment outcomes compared to well-nourished patients (AHR: 2.0, 95% CI: 1.2, 3.6). In addition, patients residing in rural areas (AHR: 3.1, 95% CI: 1.7, 5.4), having a history of prior TB treatment (AHR: 2.2, 95%CI: 1.1, 4.1), and the presence of diabetes comorbidity (AHR: 2.4, 95% CI: 1.1, 5.2) were at higher risk of unsuccessful treatment outcomes. Undernutrition increases the risk of unsuccessful treatment outcomes in Ethiopia. This finding suggests that nutritional support during TB treatment can improve successful treatment outcomes in high TB burden and low-income countries such as Ethiopia.

Safety profile of BCG revaccination for COVID prevention among elderly individuals in India

BCG vaccination is known to be safe in infants and a part of immunization schedule in high tuberculosis (TB) burden countries. In the conquest to bring down the severity of the COVID 19 pandemic, many drugs were repurposed in research mode including BCG vaccination /revaccination in various populations. We did a study among the elderly population (> 60 years of age) to assess the role of BCG revaccination in preventing the severity of COVID 19 disease. Live attenuated BCG vaccine was given to the willing participants and were followed up for 6 months to estimate COVID19 incidence, understand severity and immunogenicity profile. A total of 48 serious adverse events (SAE) were reported among 1566 elders, none of them had more than one SAE. None of the SAEs were related to the BCG revaccination. Among the 372 adverse events reported, 96% were local reactions at the vaccine site and resolved on its own. BCG revaccination appeared to be safe and could be explored further if repurposing studies were planned for other diseases.

Bridging the gap: evaluating high TB burden country data needs to support the potential introduction of TB vaccines for adolescents and adults: a workshop report

High tuberculosis (TB) burden countries (HBCs) need to prepare for TB vaccine implementation alongside licensure, to ensure rapid rollout. WHO policy/implementation frameworks have been created to support this effort. Using WHO frameworks, we convened a workshop to ask HBC experts about what epidemiological, impact, feasibility and acceptability data they anticipated they would need to guide TB vaccine introduction. For required data, we asked HBC and global experts which data were already available, data collection planned, or gaps. HBC experts expressed high demand for epidemiological, impact, feasibility and acceptability data, reported variable availability of existing epidemiological data, and low availability for impact, feasibility, and acceptability data. Global experts reported additional knowledge of existing data on impact, upcoming collection of infection prevalence, acceptability and feasibility data, and potential epidemiological data collection on adolescents, adults, people living with HIV, and underweight individuals. HBC and global experts made key recommendations for: a coordinated data collation, collection, analysis and sharing system; updating existing HBC health and economic impact estimates and extending impact analyses to other HBCs; demand/market forecasting; resource gap mapping; aligning delivery strategies; addressing manufacturing, procurement, delivery, and regulatory barriers; sharing potential vaccine licensure timing; incorporating TB vaccine introduction strategies into NSPs, immunization programs, and health services; collecting vaccine hesitancy, mistrust, and misinformation data; collecting adolescent/adult vaccine demand generation data, and identifying funding. Experts recommended expanding this analysis to other areas of the WHO frameworks, including more HBC stakeholders, and repeating this analysis after country and community advocacy and socialization around different vaccine candidates.

Spiritual Holy Water Sites in Ethiopia: Unrecognized High-Risk Settings for Transmission of Pulmonary Tuberculosis.

Ethiopia is a high-tuberculosis (TB) burden country with 157 new cases per 100,000 people, with 23,800 TB-related deaths in 2020. In Ethiopia, TB patients have different healthcare-seeking behaviors. They frequently visit spiritual places, such as holy water sites (HWSs), to seek treatment for their illness spiritually. This study examined the prevalence of pulmonary TB (PTB) and drug susceptibility profiles of Mycobacterium tuberculosis (MTB) isolates among spiritual HWS attendees in Northwest Ethiopia. A cross-sectional study was conducted from June 2019 to March 2020. Sputum samples were collected, processed, and cultured using Löwenstein-Jensen (LJ) culture medium. Second-generation line probe assays (LPAs), GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0, were used to detect anti-TB drug-resistant isolates. STATA 17 was utilized to perform descriptive statistics, bivariate, and multivariate regression analyses. Of 560 PTB-symptomatic participants, 21.8% ((95% confidence interval (95 CI): 18.4-25.2%)) were culture-positive, resulting in a point prevalence of 1,183/100,000 attendees. Amongst HWS attendees, culture-positive TB occurred most commonly in persons 18-33 years of age (28.5% (95 CI 23.4-34.3%)). Other participant characteristics significantly associated with culture-positive PTB were as follows: rural residents (adjusted odds ratio (aOR) 2.65; 95 CI 1.38-5.10), married participants (aOR 2.43; 95 CI 1.28-4.63), family members >5 per household (aOR 1.84; 95 CI 1.04-3.24), and sharing living space (aOR 10.57; 95 CI 3.60-31.13). Also, among 438 participants followed for 12 months after showing negative TB culture results while at the HWS, 6.8% (95 CI 4.4-9.4%) developed or contracted culture-positive TB post-residency at the HWSs. Of the 122 tested isolates, 20 (16.4%) were isoniazid (INH) and/or rifampicin (RIF) resistant. Multidrug-resistant (MDR) TB was detected in 15 cases (12.3%), five of which were fluoroquinolones (FLQs) resistant. The findings from this study should raise a concern about HWSs as potential high-risk settings for TB transmission. It is recommended that appropriate control measures be instituted that include compulsory TB testing and tightened infection control at HWSs, where an increased risk exists for transmission of TB.

IJCM_311A: Epidemiological profile of tuberculosis cases at an urban slum in a metropolitan city a cross sectional study

Background: The WHO Global Tuberculosis Programme works towards the goal of a world free of TB, with zero deaths, disease and suffering due to the disease. Tuberculosis (TB) is a preventable and usually curable disease. Yet in 2022, TB was the worlds second leading cause of death from a single infectious agent, after coronavirus disease (COVID-19). The reported global number of people newly diagnosed with TB was 7.5 million in 2022; this is the highest number since WHO began global TB monitoring in 1995. Around 87% of new TB cases occurred in the 30 high TB burden countries, with more than two-thirds of the global total in Bangladesh, China, Democratic Republic of the Congo, India, Indonesia, Nigeria, Pakistan and the Philippines. Objective: To study the epidemiological profile of tuberculosis cases in an urban slum of Mumbai. Methodology: A retrospective record-based analysis of secondary data on tuberculosis (pulmonary and extrapulmonary) reported on the NIKSHAY portal between January to December 2022 at an urban health training center in an urban slum in Mumbai. Results: The total number of drug sensitive TB cases reported in 2022 was 519. Males constituted 42% and females 58%. The most common age group affected was 20-29 years. Pulmonary cases comprised 66.9% of the cases. The total number of Drug resistant TB cases reported were 75, 53 were pulmonary & 22 were extrapulmonary. Conclusion: In contrast to Male predominance (52.26%) of cases in Maharashtra, the urban slum had 42% males affected. India grapples with multiple challenges in combatting tuberculosis (TB), marked by a high disease burden, diagnostic delays, drug resistance, and socioeconomic barriers. While significant strides have been made through programs like the National Tuberculosis Elimination Program, the path to eradication demands continued efforts.

Cross Sectional Study on the Prevalence of Tuberculosis among the District of Sudhnuti, Azad Jammu and Kashmir

Globally, tuberculosis (TB) is a major health risk that is mostly caused by Mycobacterium tuberculosis, a member of the Mycobacterium Tuberculosis Complex (MTC). Ten million cases of tuberculosis and 1.3 million deaths from the disease occur each year, making Mycobacterium tuberculosis one of the leading causes of death globally. Pakistan is ranked fifth among high-burden countries for tuberculosis (TB) and is expected to rank fourth for the prevalence of multi-drug resistant (MDR) TB. As a result, tuberculosis poses a serious threat to public health in Pakistan. Tuberculosis is a common occurrence in Azad Jammu and Kashmir. Aims: The current study aimed to find out the prevalence of tuberculosis in the defined population. Study Design: The study was conducted in the District and Tehsil Headquarters Hospitals of District Sudhnuti AJK. Place and Duration of Study: Samples were collected from all the District and Tehsil headquarters hospitals of Sudhnuti district from January 2019 to December 2019. Methodology: Samples of sputum from suspected cases were gathered from district Sudhnuti hospitals and TB centers from January 2019 to December 2019. All the suspected cases were examined by sputum smear microscopy and then bacteriologically positive cases were further confirmed by GeneXpert. All positive cases were examined for multi-drug resistance by using GeneXpert. Results: In the current study during the year 2019, 201 TB cases were reported from district Sudhnuti out of which 107 (53.23%) were males and 94 (46.76%) were females. The value of P=0.51 which is >0.05 is insignificant shows that Tuberculosis has no selective effect on a specific gender. Pulmonary cases were 131 in number with 81 bacteriologically positive and 50 clinically diagnosed negative cases. Extra Pulmonary cases were 70 in number with 1 bacteriologically positive and 69 clinically diagnosed negative cases. Only 2 (0.99%) MDR cases were diagnosed and the case notification rate during 2019 was 66. Conclusion: The current study shows that males are slightly more prone to TB in district Sudhnuti AJK as compared to females. Individuals with age >64 are more susceptible to TB when compared to individuals with age <15. The CNR during 2019 is 66 which is far away from the WHO set criteria. The CNR indicates that there is a need for improvement in the surveillance system.

Characteristics, knowledge, attitude, and practice of pharmacy personnel in supporting tuberculosis treatment: A multicenter cross-sectional study in a high-burden tuberculosis country

BackgroundPositive roles of community pharmacy in tuberculosis (TB) care have been widely reported. However, the actual practice of supporting TB treatment is not optimal yet. ObjectivesWe analyzed the current practice of community pharmacy personnel and its factors in supporting the successful treatment of TB patients in Indonesia, aiming to develop strategies for effective and sustainable TB practice models for the community pharmacy. MethodsWe performed a cross-sectional survey in 3 areas representing Indonesia's eastern, central, and western parts. Development and validation of the questionnaire were conducted to assess 4 domains, that is, characteristics, knowledge, attitudes, and practice of community pharmacy personnel in supporting the successful treatment of TB patients. Data were collected with purposive convenience sampling using online and offline questionnaires. Descriptive analyses were used to summarize factors in each domain, while binary logistic regression was used to analyze the associated factors of the practice. ResultsThirty-five questionnaire items indicated a valid instrument, and the study successfully included 844 participants who comprised pharmacists (n = 473, 56%) and pharmacy assistants (n = 371, 44%). Although most of the knowledge items were correctly answered by more than 60% of the participants, items related to TB signs, risk groups, drug regimens, and medicine uses were still less than 60%. This was in line with exposure to updated TB training in only 51% of the participants (n = 426). Most of the participants had a positive attitude toward their professional role (n = 736, 87%), capability (n = 646, 77%), and consequences (n = 655, 78%) in supporting TB treatment. However, this was not aligned with the actual practice of supporting TB treatment, intensively performed by only 1.3% of participants (n = 11). We identified several factors associated with the practice, that is, a pharmacy assistant background (P < 0.05), short working time (P < 0.05), experience in TB training (P < 0.001), and a positive attitude (P < 0.001). ConclusionThis study highlighted a limited number of community pharmacy personnel intensively practicing as TB treatment supporters in Indonesia. An interventional package considering the identified factors is needed to develop effective and sustainable practices in the real world.

Knowledge, attitudes, and practices towards childhood tuberculosis among healthcare workers at two primary health facilities in Lusaka, Zambia.

Zambia is among the 30 high-burden countries for tuberculosis (TB), Human Immunodeficiency Virus (HIV)-associated TB, and multi-drug resistant/rifampicin resistant TB with over 5000 children developing TB every year. However, at least 32% of the estimated children remain undiagnosed. We assessed healthcare workers' (HCWs) knowledge, attitudes, and practices (KAP) towards childhood TB and the factors associated with good KAP towards childhood TB. Data was collected at two primary healthcare facilities in Lusaka, Zambia from July to August 2020. Structured questionnaires were administered to HCWs that were selected through stratified random sampling. Descriptive analysis was done to determine KAP. A maximum knowledge, attitude, and practice scores for a participant were 44, 10, and 8 points respectively. The categorization as either "poor" or "good" KAP was determined based on the mean/ median. Logistic regression analysis was performed to assess the associations between participant characteristics and KAP at statistically significant level of 0.05%. Among the 237 respondents, majority were under 30 years old (63.7%) and were female (72.6%). Half of the participants (50.6%) were from the outpatient department (OPD) and antiretroviral therapy (ART) clinic, 109 (46.0) had been working at the facility for less than 1 year, 134 (56.5%) reported no previous training in TB. The median/mean KAP scores were 28 (IQR 24.0-31.0), 7 (IQR = 6.0-8.0) and 5 points (SD = 1.9) respectively. Of the participants, 43.5% (103/237) had good knowledge, 48.1% (114/237) had a good attitude, and 54.4% (129/237) had good practice scores on childhood TB. In the multivariate analysis, clinical officers and individuals with 1-5 years' work experience at the facility had higher odds, 2.61 (95% CI = 1.18-5.80, p = 0.018) and 3.09 (95% CI = 1.69-5.65, p = 0.001) of having good attitude respectively, and medical doctors had 0.17 lower odds (95% CI = 0.18-5.80, p = 0.018) of good childhood TB practice. Other participant characteristics didn't show a significant association with the scores. The study found suboptimal levels of knowledge, attitude, and practices regarding childhood TB among HCWs. Targeted programmatic support needs to be provided to address the above gaps.

Evaluation of Gene Xpert Test of Stool Specimen with that of Induced Sputum as Gold Standard

Background: Globally Tuberculosis (TB) is a major infectious disease. In 2011, there were an estimated 8.7 million new cases with 6% childhood tuberculosis. The majority of the cases occurring in high TB burden countries worldwide. Confirmed diagnosis of childhood TB remains challenging for physicians. MT test and Chest X-ray usually has very little diagnostic value for the diagnosis of pulmonary tuberculosis in children who has symptom criteria suggestive of PTB. Objectives: This study was done to evaluate of Gene Xpert Test of Stool Specimen with that of Induced Sputum as Gold Standard. Methods: The cross-sectional study was conducted in the Department of Pediatrics, Sir Salimullah Medical College &amp; Mitford Hospital from January 2020 to June 2021. A total of 48 subjects of both sexes with the age range from 1 month to 59 months were included in the study. Data were collected over a period of eleven months and analyzed by appropriate computer based programmed software Statistical Package for the Social Sciences (SPSS), version 22. Results: In this study, most of the children 14 (29.2%) lies between 13 months to 24 months. About most of the children 28 (58.33%) were male and 20 (41.67%) children were female. According to the clinical presentation majority of the children present with fever 39(75.0%), followed by cough (72.9%) and weight loss (50%), history of contact was present in 15 (31.3%) children. Chest X-ray of 54% children was suggestive of PTB (as Consolidation, Milliary mottling, patchy opacity etc) 46% showed normal X-ray findings. Gene X-pert of Induced sputum could detect M.Tuberculosis in case of 12.5% children and in 87.5% cases Gene X-pert could not detect M.Tuberculosis in induced sputum. M.Tuberculosis was detected by Stool X-pert in 18% of children who were clinically diagnosed as PTB. In 82% of patient stool X-pert could not detect M.Tuberculosis. Conclusion: Gene Xpert test of stool specimen is a relatively easy test for the diagnosis ........

A systematic review and meta-analysis of intraarterial chemotherapy for non muscle invasive bladder cancer: Promising alternative therapy in high tuberculosis burden countries.

Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence. Intravesical Bacillus Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC. Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results. We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC. We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study. Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p<0.001). Some RCT's had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades. The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results.

Private practitioners' practices for tuberculosis management in a city largely served by the private health sector in Uganda.

Globally, tuberculosis (TB) remains a significant cause of morbidity and mortality having caused 1.6 million deaths in 2021. Uganda is a high TB burden country with a large private sector that serves close to 60% of the urban population. However, private for-profit health facilities' involvement with the National TB and Leprosy Program (NTLP) activities remains poor. This study evaluated the practices of diagnosis and treatment of pulmonary tuberculosis (PTB) and associated factors among practitioners in private for-profit (PFP) healthcare facilities in Kampala, Uganda. We conducted a cross-sectional study among randomly selected private practitioners in Uganda's largest city, Kampala. A structured questionnaire was used for data collection. Descriptive statistics and generalized linear models with log Poisson link were used to analyze data. Practices were graded as standard or substandard. Of the 630 private practitioners studied, 46.2% (95% confidence interval (CI): 26.6 to 67.1) had overall standard practices. Being a laboratory technician (prevalence ratio (PR) = 2.7, p< 0.001) or doctor (PR = 1.2, p< 0.001), a bachelor's degree level of qualification (PR = 1.1, p = 0.021), quarterly supervision by the national TB program (PR = 1.3, p = 0.023), and acceptable knowledge of the practitioner about TB (PR = 1.8, p<0.001) were significantly associated with standard practices. The practices of TB management for practitioners from the PFP facilities in Kampala are suboptimal and this poses a challenge for the fight against TB given that these practitioners are a major source of primary health care in the city.

Care pathways of individuals with tuberculosis before and during the COVID-19 pandemic in Bandung, Indonesia.

The COVID-19 pandemic is thought to have undone years' worth of progress in the fight against tuberculosis (TB). For instance, in Indonesia, a high TB burden country, TB case notifications decreased by 14% and treatment coverage decreased by 47% during COVID-19. We sought to better understand the impact of COVID-19 on TB case detection using two cross-sectional surveys conducted before (2018) and after the onset of the pandemic (2021). These surveys allowed us to quantify the delays that individuals with TB who eventually received treatment at private providers faced while trying to access care for their illness, their journey to obtain a diagnosis, the encounters individuals had with healthcare providers before a TB diagnosis, and the factors associated with patient delay and the total number of provider encounters. We found some worsening of care seeking pathways on multiple dimensions. Median patient delay increased from 28 days (IQR: 10, 31) to 32 days (IQR: 14, 90) and the median number of encounters increased from 5 (IQR: 4, 8) to 7 (IQR: 5, 10), but doctor and treatment delays remained relatively unchanged. Employed individuals experienced shorter delays compared to unemployed individuals (adjusted medians: -20.13, CI -39.14, -1.12) while individuals whose initial consult was in the private hospitals experienced less encounters compared to those visiting public providers, private primary care providers, and informal providers (-4.29 encounters, CI -6.76, -1.81). Patients who visited the healthcare providers >6 times experienced longer total delay compared to those with less than 6 visits (adjusted medians: 59.40, 95% CI: 35.04, 83.77). Our findings suggest the need to ramp up awareness programs to reduce patient delay and strengthen private provide engagement in the country, particularly in the primary care sector.

Laboratory Diagnosis of Genital Tuberculosis: A Narrative Review

Genital tuberculosis is a leading cause of infertility in high tuberculosis burden countries like Bangladesh. Diagnosing this condition can be challenging due to the diverse ways it can present, which requires a physician to have a high level of suspicion. The fallopian tubes are mainly affected, and the endometrium in 50% of cases1. Diagnostic modalities usually include histopathology, microscopy, solid and liquid culture tests, Polymerase Chain Reaction (PCR) tests, immunohistochemistry tests, radiology imaging and laparoscopic and hysteroscopic procedures.&#x0D; Bangladesh Journal of Infectious Diseases, December 2023;10(2):92-100

A potent subset of Mycobacterium tuberculosis glycoproteins as relevant candidates for vaccine and therapeutic target

Tuberculosis (TB) remains one of the most afflictive bacterial infections globally. In high burden TB countries, surveillance, diagnosis and treatment of drug resistant TB (RR and X/MDRTB) display a crucial public health challenge. Therefore, we need new TB vaccines; diagnostic and therapeutic strategies to briskly prevent disease promotion; reduce drug-resistant TB and protect everyone from disease. The study identified various potent membrane and cell wall M. tuberculosis glycolipoproteins that are relevant for diagnostics, drug and vaccine discovery. A M. tuberculosis Proskauer and Beck broth culture was extracted for total proteins by ammonium sulfate method. After ConA-Affinity Chromatography reputed glycoproteins were collected followed by 2DE gel electrophoresis and LC Mass spectrometry. A total of 293 glycoproteins were identified using GlycoPP and IEDB database. Probable conserved trans-membrane protein (Rv0954), LpqN (Rv0583), PPE68 (Rv3873), Phosphate-binding protein (Rv0932c), PPE61 (Rv3532) and LprA (Rv1270c), had the highest glycosylation percentage value with 13.86%, 11.84%, 11.68%, 11.1%, 10.59% and10.2%, respectively. Our study discloses several dominant glycoproteins that play roles in M. tuberculosis survival, and immunogenicity. These include glycoproteins involved in antigenicity, transport and biosynthesis of M. tuberculosis cell envelope, pathogen-host interaction and drug efflux pumps, which are considered as a feasible drug targets or TB new vaccine candidates.

Strain structure analysis of Mycobacterium tuberculosis circulating among HIV negative, positive and drug resistant TB patients attending chest clinics in Western Kenya

BackgroundDespite global tuberculosis (TB) interventions, the disease remains one of the major public health concerns. Kenya is ranked 15th among 22 high burden TB countries globally.MethodsA cross-sectional study was conducted in Western Kenya, which comprises 10 counties. A multistage sampling method was used where a single sub-county was randomly selected followed by sampling two high volume health facility from each sub-county. Identification of spoligotype profiles and their family distribution and lineage level were achieved by comparison with SITVIT database.ResultsLineage distribution pattern revealed that the most predominant lineage was CAS 220 (39.8%) followed by Beijing 128 (23.1%). The other lineages identified were T, LAM, H, X, S and MANU which were quantified as 87 (15.7%), 67 (12.1%), 16 (2.8%), 10 (1.8%), 8 (1.4%) and 5 (0.9%) respectively. CAS and Beijing strains were the most predominant lineage in both HIV negative and positive TB patients. The Beijing lineage was also the most predominant in resistant M. tuberculosis strains as compared to wild type. A total of 12 (2.0%) were orphaned M. tuberculosis strains which were spread across all the 10 counties of the study site. In multivariate logistic regression adjusting for potential cofounders three potential risk factors were significant. HIV status (OR = 1.52, CI = 0.29–3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43–3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49–3.87 and P value = 0.026). Most M. tuberculosis clinical isolates showed genetic clustering with multivariate logistic regression indicating three potential risk factors to clustering. HIV status (OR = 1.52, CI = 0.29–3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43–3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49–3.87 and P value = 0.026).ConclusionThere exist diverse strains of M. tuberculosis across the 10 counties of Western Kenya. Predominant distribution of clustered genotype points to the fact that most TB cases in this region are as a result of resent transmission other than activation of latent TB.

2511. Screening for Hepatitis B Virus (HBV) and Tuberculosis (TB) Infection among Non-U.S.-Born Adults from High HBV and TB Burden Countries

Abstract Background Hepatitis B virus (HBV) infection and tuberculosis (TB) infection both disproportionately affect non-U.S.–born persons from countries with hepatitis B surface antigen (HBsAg) seroprevalence ≥2% or TB incidence rates ≥20/100,000 population. Early identification and treatment of chronic HBV and TB infection are critical to reduce morbidity and mortality, but little is known about HBV and TB screening among non-U.S.–born persons in the United States. Methods In a cross-sectional study using electronic health record data, we assessed HBV and TB infection screening practices among Kaiser Permanente Northern California eligible members aged ≥18 years born in countries with intermediate to high burdens of both HBV and TB infection. HBV screening was defined as testing for HBV surface antigen and HBV core antibody. TB infection screening was defined as testing with interferon gamma release assay or tuberculin skin test. We calculated the proportion of individuals from intermediate and high HBV-TB burden countries who had HBV or TB infection screening and the proportion of patients positive for HBV or TB infection. Results Of 498,339 non-U.S.–born adults, 275,708 (55.3%) were born in intermediate or high HBV-TB burden countries. Most patients were aged ≥50 years (65.3%) and 23.5% had diabetes. Among persons born in intermediate or high HBV-TB burden countries, 67.1% were screened for HBV infection, 29.4% were screened for TB infection, and only 23.7% were screened for both HBV and TB infection. Among all persons born in intermediate or high HBV-TB burden countries (both screened and unscreened), 3.7% had HBV infection and 10.1% had TB infection. Among 231,431 persons born in intermediate or high HBV-TB burden countries without current or prior HBV infection, 72.9% had received at least one HBV vaccine dose. Conclusion Among non-U.S.–born adults from intermediate or high HBV-TB burden countries, we found low screening proportions, intermediate prevalence of chronic HBV infection and high prevalence of TB infection. Given the large population of persons from intermediate or high HBV-TB burden countries in Kaiser Permanente Northern California, screening for both infections at the same time could improve early diagnosis and treatment for both conditions. Disclosures Jacek Skarbinski, MD, Genentech: Grant/Research Support|Gilead Sciences: Grant/Research Support Robert J. Wong, MD, MS, Gilead Sciences: Grant/Research Support

Digital health solutions and integrated COVID-19 and TB services to help recover TB care and prevention services in the COVID-19 pandemic: A descriptive study in four high TB burden countries.

The measures undertaken to control COVID-19 have disrupted many platforms including tuberculosis (TB) healthcare services. Consequently, declines in TB notifications have been observed in various countries. We visualized changes over time in TB and SARS-CoV-2 infection notifications and reported on country-specific strategies to retain TB care and prevention services in Kyrgyzstan, Nigeria, Tanzania, and Vietnam. We collected and visualized quarterly, retrospective, and country-specific data (Quarter (Q) 1 2018- Q1 2021) on SARS-CoV-2 infection and TB notifications. Additionally, we conducted a country-specific landscape assessment on COVID-19 measures, including lockdowns, operational level strategy of TB care and prevention services, and strategies employed to recover and retain those services. We used negative binomial regression models to assess the association between the installation of COVID-19 measures and changes in TB notifications. TB notifications declined in Kyrgyzstan and Vietnam, and (slightly) increased in Nigeria and Tanzania. The changes in TB notifications were associated with the installation of various COVID-19 prevention measures for Kyrgyzstan and Vietnam (declines) and Nigeria (increases). All countries reported reduced TB screening and testing activities. Countries reported the following strategies to retain TB prevention and care services: digital solutions for treatment adherence support, capacity building, and monitor & evaluation activities; adjustment in medication supply/delivery & quantity, including home delivery, pick up points, and month supply; integrated TB/COVID-19 screening & diagnostic platform; and the use of community health care workers. Following the COVID-19 pandemic, we did not observe consistent changes in TB notifications across countries. However, all countries reported lower operating levels of TB prevention and care services. Digital health solutions, community-based interventions, and the integration of COVID-19 and TB testing services were employed to recover and retain those services.

Genotypic and phenotypic comparison of drug resistance profiles of clinical multidrug-resistant Mycobacterium tuberculosis isolates using whole genome sequencing in Latvia

BackgroundMultidrug-resistant tuberculosis (MDR–TB) remains a major public health problem in many high tuberculosis (TB) burden countries. Phenotypic drug susceptibility testing (DST) take several weeks or months to result, but line probe assays and Xpert/Rif Ultra assay detect a limited number of resistance conferring gene mutations. Whole genome sequencing (WGS) is an advanced molecular testing method which theoretically can predict the resistance of M. tuberculosis (Mtb) isolates to all anti-TB agents through a single analysis.MethodsHere, we aimed to identify the level of concordance between the phenotypic and WGS-based genotypic drug susceptibility (DS) patterns of MDR–TB isolates. Overall, data for 12 anti-TB medications were analyzed.ResultsIn total, 63 MDR–TB Mtb isolates were included in the analysis, representing 27.4% of the total number of MDR–TB cases in Latvia in 2012–2014. Among them, five different sublineages were detected, and 2.2.1 (Beijing group) and 4.3.3 (Latin American-Mediterranean group) were the most abundant. There were 100% agreement between phenotypic and genotypic DS pattern for isoniazid, rifampicin, and linezolid. High concordance rate (> 90%) between phenotypic and genotypic DST results was detected for ofloxacin (93.7%), pyrazinamide (93.7%) and streptomycin (95.4%). Phenotypic and genotypic DS patterns were poorly correlated for ethionamide (agreement 56.4%), ethambutol (85.7%), amikacin (82.5%), capreomycin (81.0%), kanamycin (85.4%), and moxifloxacin (77.8%). For capreomycin, resistance conferring mutations were not identified in several phenotypically resistant isolates, and, in contrary, for ethionamide, ethambutol, amikacin, kanamycin, and moxifloxacin the resistance-related mutations were identified in several phenotypically sensitive isolates.ConclusionsWGS is a valuable tool for rapid genotypic DST for all anti-TB agents. For isoniazid and rifampicin phenotypic DST potentially can be replaced by genotypic DST based on 100% agreement between the tests. However, discrepant results for other anti-TB agents limit their prescription based solely on WGS data. For clinical decision, at the current level of knowledge, there is a need for combination of genotypic DST with modern, validated phenotypic DST methodologies for those medications which did not showed 100% agreement between the methods.

Utilization of digital tools to enhance COVID-19 and tuberculosis testing and linkage to care: A cross-sectional evaluation study among Bodaboda motorbike riders in the Nairobi Metropolis, Kenya.

Kenya has registered over 300,000 cases of COVID-19 and is a high-burden tuberculosis country. Tuberculosis diagnosis was significantly disrupted by the pandemic. Access to timely diagnosis, which is key to effective management of tuberculosis and COVID-19, can be expanded and made more efficient through integrated screening. Decentralized testing at community level further increases access, especially for underserved populations, and requires robust systems for data and process management. This study delivered integrated COVID-19 and tuberculosis testing to commercial motorbike (Bodaboda) riders, a population at increased risk of both diseases with limited access to services, in four counties: Nairobi, Kiambu, Machakos and Kajiado. Testing sheds were established where riders congregate, with demand creation carried out by the Bodaboda association. Integrated symptom screening for tuberculosis and COVID-19 was conducted through a digital questionnaire which automatically flagged participants who should be tested for either, or both, diseases. Rapid antigen-detecting tests (Ag-RDTs) for COVID-19 were conducted onsite, while sputum samples were collected and transported to laboratories for tuberculosis diagnosis. End-to-end patient data were captured using digital tools. 5663 participants enrolled in the study, 4946 of whom were tested for COVID-19. Ag-RDT positivity rate was 1% but fluctuated widely across counties in line with broader regional trends. Among a subset tested by PCR, positivity was greater in individuals flagged as high risk by the digital tool (8% compared with 4% overall). Of 355 participants tested for tuberculosis, 7 were positive, with the resulting prevalence rate higher than the national average. Over 40% of riders had elevated blood pressure or abnormal sugar levels. The digital tool successfully captured complete end-to-end data for 95% of all participants. This study revealed high rates of undetected disease among Bodaboda riders and demonstrated that integrated diagnosis can be delivered effectively in communities, with the support of digital tools, to maximize access.