Routine tuberculosis contact investigation yield and preventive treatment cascade in central Ethiopia.

Introduction: There is a global gap between tuberculosis incident cases and the notified cases. Active household contact investigation is one of the strategies to narrow this gap. It has the advantage of giving early diagnosis and preventive treatment to vulnerable and eligible groups. This study assessed the practice of contact investigation and tuberculosis preventive treatment adherence in central Ethiopia. Method: A cross-sectional study covering all registered bacteriologically confirmed pulmonary tuberculosis patients and their close contacts was conducted in central Ethiopia from January 1, 2022, to December 30, 2022. Result: A total of 1372 household contacts were declared by the index cases. From these 79.44 % (1090) contacts received a one-time tuberculosis screening giving a total of four (0.36 %) active TB cases. Among 484 household contacts of drug-resistant tuberculosis index cases, 5.53 % (14) had presumptive tuberculosis and 0.79 % (2) had active tuberculosis. While among 837 household contacts of drug-susceptible tuberculosis index cases presumptive TB cases were 1.91 % (16) and active TB cases were 0.23 % (2). Of the 142 eligible under 15 children 81.69 % (116) had started tuberculosis preventive treatment and 84.48 % (98) completed the treatment. On multivariable logistic regression, the associated factor for tuberculosis preventive treatment non-adherence was age 2-5 years (aOR, 0.02, 95 % CI (0.002-0.20) and age 5-15 years (aOR, 0.04,95 % CI (0.002-0 0.95)) P=<0.05). Conclusion: There was low contact screening practice in the DR-TB index cases as compared to national and global targets. The yield of routine contact investigation was low and it indicates the quality of screening. Tuberculosis preventive treatment initiation and completion rates were also low as compared to those of many other countries and global achievements which need further improvement, especially for completion. Alternative mechanisms should be planned to increase the yield of tuberculosis screening and tuberculosis preventive treatment adherence.

A smooth tubercle bacillus from Ethiopia phylogenetically close to the Mycobacterium tuberculosis complex.

The Mycobacterium tuberculosis complex (MTBC) includes several human- and animal-adapted pathogens. It is thought to have originated in East Africa from a recombinogenic Mycobacterium canettii-like ancestral pool. Here, we describe the discovery of a clinical tuberculosis strain isolated in Ethiopia that shares archetypal phenotypic and genomic features of M. canettii strains, but represents a phylogenetic branch much closer to the MTBC clade than to the M. canettii strains. Analysis of genomic traces of horizontal gene transfer in this isolate and previously identified M. canettii strains indicates a persistent albeit decreased recombinogenic lifestyle near the emergence of the MTBC. Our findings support that the MTBC emergence from its putative free-living M. canettii-like progenitor is evolutionarily very recent, and suggest the existence of a continuum of further extant derivatives from ancestral stages, close to the root of the MTBC, along the Great Rift Valley.

The prevalence of latent tuberculosis infection in patients with chronic kidney disease: A systematic review and meta-analysis.

Objective: To estimate the prevalence of latent tuberculosis infection (LTBI) in chronic kidney disease (CKD) patients. Methods: This study was conducted following the PRISMA guidelines. We identified, 3694 studies from the whole search, and 59 studies were included. Each study's quality was assessed using JBI checklist. We employed STATA version 17 for statistical analysis. We assessed heterogeneity using I2 heterogeneity test. Publication bias was assessed using funnel plot and Egger's test. We estimated the pooled LTBI prevalence in CKD patients along with 95%CI. Results: The pooled prevalence of LTBI among CKD patients using data collected from 53 studies having 12,772 patients was 30.2% (95%CI; 25.5, 34.8). The pooled prevalence among pre-dialysis, hemodialysis, peritoneal dialysis, and renal transplanted patients was 17.8% (95%CI; 3.3, 32.4), 34.8% (95%CI; 29.1, 40.5), 25% (95%CI; 11, 38), and 16% (95%CI; 7, 25), respectively. The pooled prevalence of LTBI stratified by the laboratory screening methods was 25.3% (95%CI: 20.3-30.3) using TST, 28.0% (95%CI; 23.9-32.0) using QFT, and 32.6%, (95%CI: 23.7-41.5) using T-SPOT. Conclusion: There is high prevalence of LTBI among CKD patients mainly in patients on dialysis. Thus, early diagnosis and treatment of LTBI in CKD patients should be performed to prevent active TB in CKD patients.PROSPERO registration number: CRD42022372441.

Poor treatment outcome and associated risk factors among patients with isoniazid mono-resistant tuberculosis: A systematic review and meta-analysis.

BACKGROUND: To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies have assessed the treatment outcome of isoniazid mono-resistant TB cases, however, the findings are inconsistent and there is limited global comprehensive report. Thus, this study aimed to assess the poor treatment outcome and its associated risk factors among patients with isoniazid mono-resistant TB. METHODS: Studies that reported the treatment outcomes and associated factors among isoniazid mono-resistant TB were searched from electronic databases and other sources. We used Joana Briggs Institute critical appraisal tool to assess the study's quality. We assessed publication bias through visual inspection of the funnel plot and confirmed by Egger's regression test. We used STATA version 17 for statistical analysis. RESULTS: Among 347 studies identified from the whole search, data were extracted from 25 studies reported from 47 countries. The pooled successful and poor treatment outcomes were 78% (95%CI; 74%-83%) and 22% (95%CI; 17%-26%), respectively. Specifically, complete, cure, treatment failure, mortality, loss to follow-up and relapse rates were 34%(95%CI; 17%-52%), 62% (95%CI; 50%-73%), 5% (95%CI; 3%-7%), 6% (95%CI; 4%-8%), 12% (95%CI; 8%-17%), and 1.7% (95%CI; 0.4%-3.1%), respectively. Higher prevalence of pooled poor treatment outcome was found in the South East Asian Region (estimate; 40%, 95%C; 34%-45%), and African Region (estimate; 33%, 95%CI; 24%-42%). Previous TB treatment (OR; 1.74, 95%CI; 1.15-2.33), having cancer (OR; 3.53, 95%CI; 1.43-5.62), and being initially smear positive (OR; 1.26, 95%CI; 1.08-1.43) were associated with poor treatment outcome. While those patients who took rifampicin in the continuation phase (OR; 0.22, 95%CI; 0.04-0.41), had extrapulmonary TB (OR; 0.70, 95%CI; 0.55-0.85), and took second-line injectable drugs (OR; 0.54, 95%CI; 0.33-0.75) had reduced risk of poor treatment outcome. CONCLUSION: Isoniazid mono-resistant TB patients had high poor treatment outcome. Thus, determination of isoniazid resistance pattern for all bacteriologically confirmed TB cases is critical for successful treatment outcome. PROSPERO registration number: CRD42022372367.

Incidence and predictors of acquired resistance to second-line antituberculosis drugs during the course of multi-drug resistant tuberculosis treatment: protocol for a systematic review and meta-analysis.

INTRODUCTION: To date, acquired resistance to second-line antituberculosis drugs (SLDs) during multi-drug resistant tuberculosis (MDR-TB) treatment is becoming a public health concern. Different studies have assessed the incidence of acquired resistance to SLDs. However, the findings are inconsistent and there is limited global evidence. Thus, we are going to assess the incidence and predictors of acquired resistance to SLDs during MDR-TB treatment. METHODS AND ANALYSIS: We designed this protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Electronic databases and grey literature sources will be searched systematically for articles published up to 25 March 2023. Studies reporting the incidence and predictors of acquired resistance to SLDs in MDR-TB patients will be explored. The studies will be managed using Endnote X8 citation manager and a stepwise approach will be followed to select studies. Data will be summarised using Microsoft Excel 2016 spreadsheet. A Newcastle-Ottawa Scale quality assessment and cochrane risk-of-bias tools will be used to assess the study's quality. The authors will independently search databases, select studies, assess the study's quality and extract data. Data will be analysed using STATA V.17 software. We will estimate the pooled incidence of acquired resistance with 95% CI. In addition, the pooled effect measures (OR, HR, risk ratio) with their 95% CI will be estimated. Heterogeneity will be assessed using the I2 statistics. Publication bias will be assessed using funnel plot and Egger's test. A subgroup analysis will be conducted for the primary outcome (acquired resistance) per each study characteristics such as WHO regional category, country's TB/MDR-TB burden, data collection period and per the specific second-line anti-TB drug. ETHICS AND DISSEMINATION: Since this study will be based on data extraction from published studies, ethical approval is not mandatory. The study will be published in peer-reviewed scientific journals and the findings will be presented at different scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42022371014.

Microbiological diagnosis and mortality of tuberculosis meningitis: Systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) which is caused by Mycobacterium tuberculosis poses a significant public health global treat. Tuberculosis meningitis (TBM) accounts for approximately 1% of all active TB cases. The diagnosis of Tuberculosis meningitis is notably difficult due to its rapid onset, nonspecific symptoms, and the difficulty of detecting Mycobacterium tuberculosis in cerebrospinal fluid (CSF). In 2019, 78,200 adults died of TB meningitis. This study aimed to assess the microbiological diagnosis TB meningitis using CSF and estimated the risk of death from TBM. METHODS: Relevant electronic databases and gray literature sources were searched for studies that reported presumed TBM patients. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools designed for prevalence studies. Data were summarized using Microsoft excel ver 16. The proportion of culture confirmed TBM, prevalence of drug resistance and risk of death were calculated using the random-effect model. Stata version 16.0 was used perform the statistical analysis. Moreover, subgroup analysis was conducted. RESULTS: After systematic searching and quality assessment, 31 studies were included in the final analysis. Ninety percent of the included studies were retrospective studies in design. The overall pooled estimates of CSF culture positive TBM was 29.72% (95% CI; 21.42-38.02). The pooled prevalence of MDR-TB among culture positive TBM cases was 5.19% (95% CI; 3.12-7.25). While, the proportion of INH mono-resistance was 9.37% (95% CI; 7.03-11.71). The pooled estimate of case fatality rate among confirmed TBM cases was 20.42% (95%CI; 14.81-26.03). Based on sub group analysis, the pooled case fatality rate among HIV positive and HIV negative TBM individuals was 53.39% (95%CI; 40.55-66.24) and 21.65% (95%CI;4.27-39.03) respectively. CONCLUSION: Definite diagnosis of TBM still remains global treat. Microbiological confirmation of TBM is not always achievable. Early microbiological confirmation of TBM has great importance to reduce mortality. There was high rate of MDR-TB among confirmed TBM patients. All TB meningitis isolates should be cultured and drug susceptibility tested using standard techniques.

Tuberculosis in household contacts of tuberculosis patients in sub-Saharan African countries: A systematic review and meta-analysis.

Background: The Mycobacterium tuberculosis complex causes tuberculosis, a severe public health problem. Close contacts of someone who has active pulmonary tuberculosis were at a greater risk of contracting the disease. Despite the large number of primary research available in Sub-Saharan African nations, there are no systematic reviews or meta-analyses that estimate the pooled prevalence of tuberculosis among tuberculosis patients' household contacts (HHC). Thus, this study aimed to estimate the pooled prevalence of tuberculosis in a household contact of tuberculosis patients in the sub-Saharan African region. Methods: Potential papers were systematically searched from electronic databases (PubMed, Google scholar and web of science). To analyze the quality of the papers featured, we used the Joanna Briggs Institute Critical Appraisal methods. Data were analyzed using STATA Version 16. Result: After screening 373 studies, the final analysis includes 20 articles from twelve countries. The overall prevalence of tuberculosis among household contacts was 3.29 % (95 % CI; 2.35 %-4.23 %). The overall prevalence rate of active tuberculosis in children aged less than five years was 2.60 % (95 % CI; 1.81 %-3.39 %). When the index patient age was less than 18 years old, the pooled prevalence of active TB in HHC was 2.64 % (95 % CI; 1.46 %-3.81 %). The pooled proportion of HIV in index TB patients was 53.12 % (95 % CI, 39.73 %-66.51 %). The overall pooled prevalence of HIV in household contacts was 7.75 % (95 % CI, 4.21 %-11.29 %). Conclusion: Our systematic review showed that, in Sub-Saharan African nations, household contacts are at a high risk of contracting tuberculosis from their index patient. According to this study, one out of every thirty household contacts will develop active tuberculosis. This demonstrated the significance of doing thorough active tuberculosis case tracing in household contacts to locate missing tuberculosis patients.

Tuberculosis in individuals who recovered from COVID-19: A systematic review of case reports.

BACKGROUND: The emergence of COVID-19 overwhelmed tuberculosis (TB) prevention and control, resulting in a decrease in TB detection rate and an increase in TB deaths. Furthermore, the temporary immunosuppressive effects, lung inflammation, and the corticosteroids used to treat COVID-19, may play a direct role in immunosuppression, leading to reactivation of either previous infection or latent TB or the development of new TB. Thus, the aim of this study was to review TB incidence in individuals who recovered from COVID-19. METHODS: We conducted a systematic search of available databases for previously published studies that reported TB in COVID-19 survivors. The PRISMA checklist was used to guide the review, and the JBI checklist was used to evaluate the study's quality. The descriptive data were summarized. RESULTS: Data were extracted from 21 studies conducted in 13 countries having 33 cases. The median age was 44 years (range; 13.5-80), and more than half (18, 54.5%) were males. Twelve patients immigrated from TB endemic settings. All 17 patients assessed for HIV were seronegative, and all 11 patients assessed for BCG vaccination status were vaccinated. The majority (20, 69%) of patients had some type of comorbidity with diabetes (12/29) and hypertension (9/29) being the most common. Four patients (30.77%) had a history of TB. Corticosteroids were used to treat COVID-19 in 62.5% (10) of individuals. Dexamethasone, remdesivir, azithromycin, hydroxychloroquine, and enoxaparin were the most commonly used drugs to treat COVID-19. The most common TB symptoms were fever, cough, weight loss, dyspnea, and fatigue. Twenty, eleven, and two patients developed pulmonary, extrapulmonary, and disseminated/miliary TB respectively. It may take up to seven months after COVID-19 recovery to develop tuberculosis. Data on the final treatment outcome was found for 24 patients, and five patients died during the anti-TB treatment period. CONCLUSION: Tuberculosis after recovering from COVID-19 is becoming more common, potentially leading to a TB outbreak in the post-COVID-19 era. The immunosuppressive nature of the disease and its treatment modalities may contribute to post COVID-19 TB. Thus, we recommend a further study with a large sample size. Furthermore, we recommend feasibility studies to assess and treat latent TB in COVID-19 patients residing in TB endemic counties since treatment of latent TB is done only in TB non-endemic countries.

Detection of Mycobacterium tuberculosis and rifampicin resistance by Xpert® MTB/RIF assay among presumptive tuberculosis patients in Addis Ababa, Ethiopia from 2014 to 2021.

Objective: This study aimed to determine the frequencies and trends of Mycobacterium tuberculosis and rifampicin resistance among presumptive tuberculosis patients in Ethiopia, who were tested using the Xpert MTB/RIF assay between 2014 and 2021. Methods: Data were collected retrospectively from patient registries. Laboratory-based data were extracted from the national tuberculosis (TB) referral laboratory database. All patients referred to the National Tuberculosis Reference Laboratory (NTRL) for TB diagnosis from all over the country between March 1, 2014 and September 30, 2021, and tested using the Xpert MTB/RIF assay, were included. The extracted data were entered into a Microsoft Excel sheet and analyzed by Statistical Package for Social Sciences (SPSS) version 23. Results: Among a total of 13 772 individuals tested using the Xpert MTB/RIF assay, the majority (8223; 59.7%) were males, and 48.5% (6678) of the individuals were aged between 15 and 39 years. Mycobacterium tuberculosis (MTB) was detected in 17.0% (2347) of the examined individuals. Of the detected MTB cases, nearly 9.9% (233) were rifampicin resistant (RR-TB), while 24 (1.0%) were RR-intermediate. Among all RR-TB cases, more than half (125; 53.6%) were detected in males, and 105 were new TB cases. Extrapulmonary (EPTB) patients had a greater rate of rifampicin resistance (11.0%) than pulmonary (PTB) patients (9.6%). Conclusion: The frequency of TB and RR-TB remains high in the study setting. RR-TB was found to have a statistically significant association with previous anti-TB medication treatment. As a result, improving treatment adherence in recognized instances could assist in preventing MTB and RR-TB cases.

Drug sensitivity of clinical isolates of Mycobacterium tuberculosis and its association with bacterial genotype in the Somali region, Eastern Ethiopia.

Background: Drug resistance is becoming a major bottleneck for tuberculosis (TB) control programs in countries with high TB burdens. Although several studies were conducted on the drug sensitivity of Mycobacterium tuberculosis (M. tuberculosis) in central Ethiopia, there is a lack of data on the drug sensitivity of M. tuberculosis in the peripheral regions of the country including in the Somali region. Therefore, the objective of this study was to evaluate the drug sensitivity of M. tuberculosis and its association with bacterial genotype and evaluate the performance of Xpert MTB/RIF (Xpert) in detecting resistance to rifampicin (RIF). Methods: A total of 302 M. tuberculosis were tested using the BD BACTEC-Mycobacteria Growth Indicator Tube 960 (MGIT 960) system for their drug sensitivity to the first-line anti-TB drugs. Besides, the drug sensitivity of 10 multidrug-resistant (MDR) M. tuberculosis isolates was evaluated for the second-line anti-TB drugs. Additionally, 177 of the 302 isolates were tested for genotypic drug resistance using Xpert. Chi-square and Fisher's exact tests were used for the evaluation of the association between variables and drug sensitivity. Results: The overall prevalence of resistance to at least one drug was 11.6% (95% CI: 7.9-15.2%), while the prevalence of MDR was 3.3% (95% CI: 1.3-5.3%). Two of the 10 MDR isolates were resistant to capreomycin. The spoligotype Shared International Type (SIT) 149 was significantly associated with either monoresistance or MDR (p < 0.05). Of the 177 isolates tested by Xpert, 6.2% (11/177) were RIF-resistant. Discordant between Xpert and MGIT 960 was observed in one isolate and linked with probe-binding delay (ΔCT max = 5.8). The sensitivity and specificity of the Xpert assay were 100 and 99.4%, respectively, while its positive and negative predictive values were 90.9 and 100%, respectively. Conclusion: The magnitude of MDR M. tuberculosis in the Somali region of Ethiopia was higher than the national prevalence of MDR-TB warranting the strengthening of the TB control program in the Somali region. Besides, drug resistance was associated with SIT 149 spoligotype (genotype). The Xpert assay was observed to have high sensitivity and specificity in detecting RIF-resistant M. tuberculosis, which is encouraging for its application widely.

Pre-extensively drug-resistant tuberculosis among multidrug-resistant tuberculosis patients in Ethiopia: a laboratory-based surveillance study.

Background: The rise of drug-resistant tuberculosis (DR-TB) has presented a substantial challenge to the national tuberculosis (TB) control program. Understanding the epidemiology of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) could help clinicians to adapt MDR-TB treatment regimens at an earlier stage. This study aimed to assess second-line anti-TB drug resistance among MDR-TB patients in Ethiopia using routine laboratory-based data. Methods: Laboratory-based cross-sectional data were collected from the national TB reference laboratory and seven regional tuberculosis culture laboratories in Ethiopia from July 2019 to March 2022. The required data, such as drug-susceptibility testing (DST) results and sociodemographics, were collected on a structured checklist from laboratory registration books and electronic databases. Data were entered into a Microsoft Excel spreadsheet and analyzed using SPSS version 23. Descriptive statistics were performed to show the distribution and magnitude of drug resistance. Results: Second-line drugs (SLDs) susceptibility testing was performed for 644 MDR isolates, of which 19 (3%) were found to be pre-XDR-TB cases. Of the total MDR-TB isolates, 19 (3%) were resistant to at least one fluoroquinolone drug, while 11 (1.7%) were resistant to at least one injectable second-line drug. Of the 644 MDR-TB isolates, 1.9% (5/261) pre-XDR were from new MDR-TB cases, while 3.7% (14/383) were from previously treated MDR-TB patients. The most frequently identified mutations, based on MTBDRsl results, were in codon A90V of the gyrA gene (77.3%) and A1401G of the rrs gene (45.5%). Conclusion: The overall prevalence of pre-XDR-TB in Ethiopia is considerable. The majority of SLD resistance mutations were in the gyrA gene at position A90V. Modern, rapid DST is necessary to enable identification of pre-XDR-TB and XDR-TB in supporting proper regimen administration for patients.

Effect of sputum quality and role of Xpert® MTB/ RIF assay for detection of smear-negative pulmonary tuberculosis in same-day diagnosis strategy in Addis Ababa, Ethiopia.

Background: There is limited information on the performance of the Xpert® MTB/RIF test for diagnosis of smear-negative pulmonary tuberculosis (SNPT) and rifampicin resistance (RR) in the same-day diagnosis approach. The effects of sputum quality and other factors affecting the Xpert performance are also under-investigated. Objective: This study aimed to determine the performance of the Xpert® MTB/RIF test for detection of SNPT and RR in the same-day diagnosis strategy and the effect of sputum quality and other factors on its performance. Methods: A cross-sectional study was conducted from August 2017 to January 2018 across 16 health facilities in Addis Ababa, Ethiopia. Two spot sputum samples were collected from 418 presumptive SNPT patients, tested with Xpert® MTB/RIF, then compared to tuberculosis culture. Additionally, culture isolates were tested for RR by BACTEC MGIT™ 960 drug susceptibility testing (DST) and MTBDRplus version 2. Results: The Xpert® MTB/RIF test detected 24 (5.7%) SNPT cases, with a sensitivity of 92.3% (75.9% - 97.9%) and specificity of 99.2% (97.8% - 99.7%) compared with tuberculosis culture. Xpert® MTB/RIF also detected three (11.58%) RR strains with 100.0% concordance with BACTEC MGIT™ 960 DST and MTBDRplus results. Three blood-stained SNPT samples were positive by Xpert (30.0%), which was 6.9 times higher compared to salivary sputum (odds ratio: 6.9, 95% confidence interval: 1.36-34.96, p = 0.020). Conclusion: The performance of the Xpert® MTB/RIF to detect SNPT and RR in same-day diagnosis is high. However, SNPT positivity varies among sputum qualities, and good sample collection is necessary for better test performance.

Value of urine-based lipoarabinomannan (LAM) antigen tests for diagnosing tuberculosis in children: systematic review and meta-analysis.

Background: Tuberculosis (TB) is a global burden, and this is likely to remain the case due to a lack of adequate and accurate point-of-care diagnostic tests. Obtaining good-quality sputum from the bottom of the respiratory tract of children is challenging. Lipoarabinomannan (LAM) is a specific component of the mycobacterial cell envelope that is excreted in the urine of people with active TB. This study aimed to assess the performance of different types of urine-based LAM antigen tests for the diagnosis of TB in children. Methods: Relevant databases were searched for studies that used urine-based LAM tests to diagnose TB in children. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tool. Pooled sensitivity and specificity were calculated using the random-effect model in STATA Version 16.0. Moreover, subgroup analysis was undertaken to hinder the heterogeneity of the studies. Results: Eleven articles were included in the final systematic review and meta-analysis. The pooled sensitivity and specificity of the Mycobacterium tuberculosis enzyme-linked immunosorbent assay (MTB-LAM-ELISA), Alere Determine TB LAM Ag (Alere LAM) test and the Fujifilm SILVAMP TB LAM (Fuji LAM) test in children aged <15 years with TB were 16.0% [95% confidence interval (CI) 10.25-42.25] and 95.61% (95% CI 93.74-97.74); 45.90% (95% CI 40.40-51.40) and 80.42% (95% CI 69.39-91.46); and 52.32% (95% CI 35.03-69.62) and 89.37% (95% CI 82.88-95.86), respectively. Subgroup analysis revealed that the pooled sensitivity and specificity of MTB-LAM-ELISA, Alere LAM test and Fuji LAM test were 33.5% (95% CI 34.86-100) and 95.83% (95% CI 91.50-100); 46.59% (95% CI 32.98-60.19) and 76.45% (95% CI 57.07-95.82); and 57.89% (95% CI 48.44-67.35%) and 87.66% (95% CI 75.29-100), respectively, in human immunodeficiency virus (HIV)-positive children; and 3.35% (95% CI 1.61-8.31) and 96.0% (95% CI 93.88-98.11); 32.33% (95% CI 7.63-57.03) and 79.07% (95% CI 62.62-95.51); and 50.95% (95% CI 27.45-74.45) and 89.47% (95% CI 84.72-94.22), respectively, in HIV-negative children. Conclusion: The Fuji LAM and Alere LAM tests may be useful for the diagnosis of TB in children in conjunction with other more sensitive and specific tests, although a prospective study in relevant clinical settings is needed to evaluate this. There is a need for more evidence-based data on the use of these rapid diagnostic tools to diagnose TB in children independent of HIV status.

Quality assurance practices in tuberculosis diagnostic health facilities in Ethiopia.

INTRODUCTION: The quality of tuberculosis laboratory services in health facilities is a mandatory component of detecting active pulmonary TB cases and treatment follow-up. However, ensuring the quality of laboratory test results is a concern. This study aimed to assess the quality assurance practices in the tuberculosis diagnostic health facilities of Ethiopia. MATERIALS AND METHODS: A cross-sectional study was conducted from October 2018 to March 2019 at nine governmental TB-culture laboratories and 34 randomly selected GeneXpert® MTB/RIF (Xpert® MTB/RIF) testing health facilities in Ethiopia. Participating health facilities were interviewed and laboratory documents and records present since 2017 were observed. Prior to the data collection, training was given to the data collectors. Descriptive statistics were used to produce results and were presented with tables and graphs. RESULTS: From a total of 34 Xpert® MTB/RIF testing laboratories, 50% run Internal Quality Control (IQC) for Acid-Fast Bacillus (AFB) Microscopy and 67.6% had lot-to-lot verification of staining reagents. For the Xpert® MTB/RIF assay, a lot-to-lot verification of cartridge and method validation was performed only in 8.8%and 20.6% of Xpert® MTB/RIF testing laboratories respectively. All TB-culture laboratories included in the study ran negative control (start and end IQC) during TB-culture sample processing and performed lot-to-lot verification for Mycobacteria Growth Indicator Tube (MGIT) in 88.9% of TB-culture laboratories. External Quality Assessment (EQA) Proficiency Testing (PT) for AFB microscopy is practiced in 79.4% Xpert® MTB/RIF testing laboratories and 100.0% for the Xpert® MTB/RIF assay. TB-Culture PT participation practice among TB-culture laboratories was 88.9%. A major challenge for health facilities during PT participation was the AFB PT-sample transportation delay (40.7%) and the Xpert® MTB/RIF assay EQA-PT feedback missing (38.2%). CONCLUSION: This assessment reveals that IQC for AFB microscopy, lot-to-lot verification, method validation, and equipment calibration were not well-practiced. The majority of TB diagnostic health facility laboratories had EQA-PT participation practice, but a significant gap in PT-sample transportation and missing feedback was identified.

Tuberculosis incidence in patients with chronic kidney disease: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to estimate global TB incidence in patients with CKD. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was followed to perform the study. Electronic and gray literature sources were investigated for studies published between 2000 and 2021. The Joanna Briggs Institute critical appraisal checklist was used to assess the quality of the studies, and STATA version 16 was used for analysis. The I2 heterogeneity test was employed to assess heterogeneity. To examine publication bias, funnel plots and Egger's regression tests were performed. RESULTS: A total of 104 studies with a sample size of 1,548,774 were included. TB incidence in patients with CKD ranges from 60 per 100,000 in the UK to 19,270 per 100,000 in China. The pooled TB incidence was estimated as 3718 per 100,000 (95%CI; 3024, 4411). Higher pooled TB incidence was found in the African region (9952/100,000, 95%CI; 6854, 13,051), followed by the South-East Asian (7200/100,000, 95%CI; 4537, 9863) and Eastern Mediterranean (5508/100,000, 95%CI; 3470, 7547) regions. In particular, patients on hemodialysis (5611/100,000) and on peritoneal dialysis (3533/100,000) had higher incidence of TB than did renal transplantation patients (2700/100,000) and patients with predialysis CKD (913/100,000). Furthermore, extrapulmonary TB (2227/100,000) was more common than pulmonary TB (1786/100,000). CONCLUSION: This study identifies high TB incidence in patients with CKD with regional disparities. Thus, the authors recommend active TB screening in this group of individuals.

Diagnostic accuracy of Truenat Tuberculosis and Rifampicin-Resistance assays in Addis Ababa, Ethiopia.

BACKGROUND: Rapid and sensitive Tuberculosis (TB) diagnosis closer to patients is a key global TB control priority. Truenat assays (MTB, MTB Plus, and MTB-RIF Dx) are new TB molecular diagnostic tools for the detection of TB and Rifampicin (RIF)-resistance from sputum samples. The diagnostic accuracy of the assays is needed prior to implementation in clinical use in Ethiopia. This study aimed to determine the sensitivity and specificity of Truenat assays; and aimed to compare the assays to the Xpert MTB/RIF assay. METHODS: A prospective evaluation study was conducted among 200 presumptive TB patients in microscopy centers in Addis Ababa, Ethiopia from May 2019 to December 2020. Culture (Solid and Liquid methods) and phenotypic (liquid method) drug susceptibility testing (DST) were used as a reference standard. RESULTS: Of 200 adult participants, culture confirmed TB cases were 25 (12.5%), and only one isolate was resistant to RIF by phenotypic DST. The sensitivity of Truenat MTB was 88.0% [95% CI 70.1, 95.8], while 91.7 [95% CI 74.2, 97.7] for Truenat MTB Plus at the microscopy centers. The specificity of Truenat MTB was 97.2% [95% CI 93.1, 98.9], while for Truenat MTB Plus was 97.2% [95% CI 93.0, 99.0]. The sensitivity of Truenat MTB was 90.5% while for MTB Plus, 100% compared to the Xpert MTB/RIF assay. CONCLUSION: Truenat assays were found to have high diagnostic accuracy. The assays have the potential to be used as a point of care (POC) TB diagnostic tests.

The Epidemiology of first and second-line drug-resistance Mycobacterium tuberculosis complex common species: Evidence from selected TB treatment initiating centers in Ethiopia.

BACKGROUND: Drug-resistance in Mycobacterium tuberculosis complex remains a major health burden in human history and still is a major leading cause of death in developing countries including Ethiopia. Early detection of all forms of drug-resistant Tuberculosis(TB) is a key factor to reduce and contain the spread of these resistant strains. METHODS: A health facility-based cross-sectional study was employed, based on demographic, clinical, and laboratory data collected from 204 patients with bacteriological confirmed TB. Sputum samples were analyzed using conventional TB culture and identification test followed by molecular species identification, and then phenotypic drug susceptibility tests. Data were entered using an excel spreadsheet and exported to SPSS version 20 for analysis. Descriptive analysis; frequencies, and proportions were computed. RESULTS: Among the 204 sputum samples inoculated in culture media, Mycobacterium species were recovered from 165 specimens, with 160 Mycobacterium tuberculosis complex and five Non- Tuberculosis Mycobacterium(NTM) species. All Mycobacterium tuberculosis complex was found to be M. tuberculosis. Of the five NTM species, 2 M.fortuitum, 2 M.intracellulare, and 1 M.gordonae were identified. Among 160 species of M. tuberculosis isolates, 110(68.8%) were resistant to any of the anti-TB drugs. The resistance pattern was; INH (109, 68.1%), RIF (99, 61.9%), STM (73,45.6%), and EMB (32,20.0%). Mono-resistance was found for INH (7,4.3%) and STM (1,0.6%). Ninety-nine (61.9%) isolates become MDR, while resistance to any of the second-line anti-TB drugs was detected in 9 (5.6%) strains, with 8(5%) Pre-XDR and one (0.6%) XDR cases. CONCLUSION: Our findings highlight high frequencies of drug resistance to first and second-line anti-TB drugs.Determining the drug-resistance pattern of MTB is important for programmatic management of drug-resistant TB in Ethiopia. The circulating Pre-XDR and XDR case identified in the current study is alarming to the tuberculosis control program in the country.

Adherence to Isoniazid Preventive Therapy among Under-Five Children in Contact with Adult Bacteriologically Confirmed Pulmonary Tuberculosis Patients: A Mixed-Method Study.

BACKGROUND: The World Health Organization recommends that all children below the age of five who have household contact with an infectious tuberculosis case should receive isoniazid preventive treatment for at least six months after the active tuberculosis disease has been ruled out. This research aims to determine the adherence of children, eligible for isoniazid preventive treatment, to the treatment who had contact with pulmonary tuberculosis patients. METHODS: A mixed study design was used to prospectively assess the adherence to IPT among children under the age of 5 in contact with pulmonary TB patients through the quantitative study design and barriers of adherence in view of health care professionals and the family of children through a descriptive qualitative study. The study was conducted from July 2019 to December 2019 in Addis Ababa. Data were collected by a structured datasheet from the selected health center registration book. Data were entered into Epi Data software and analyzed by using SPSS version 20. Descriptive statistical methods were used to summarize the sociodemographic characteristics of the study participants. RESULT: The ratio of the total number of pulmonary tuberculosis index cases recruited into the study to the number of child contacts aged less than 5 years was 1 : 1.32. The total isoniazid preventive treatment uptake in this study was 75.2%; one-fifth (21.3%) of the children who started IPT did not complete the full course of six-month isoniazid preventive treatment. Except for HIV not to be tested (P < 0.001), there was no significant association of the listed risk factors in default to complete the full six months of preventive treatment. CONCLUSION: Enrolment of eligible children for isoniazid preventive treatment in the urban city Addis Ababa was still below the target of the World Health Organization End tuberculosis strategy by 2030. The treatment adherence rate also needs a great deal of effort to achieve the strategy. Child default after the first visit indicates a lack of understanding about the benefit and safety of preventive therapy in young children among families of TB patients, and awareness-creating efforts by health extension workers will help to improve the outcomes.

Undernutrition and Mortality among Adult Tuberculosis Patients in Addis Ababa, Ethiopia.

BACKGROUND: In developing countries, there are several adult tuberculosis (TB) patients suffering from profound undernutrition. Undernutrition is a significant risk factor for developing tuberculosis. In the world, TB is one of the top ten and leading causes of death. To appropriately intervene death of adult TB patients, it is crucial to understand the magnitude of undernutrition and its associated factors among them. The study assessed undernutrition and mortality among adult tuberculosis patients in Addis Ababa, Ethiopia. METHODS: Institutional-based retrospective study was conducted in Addis Ababa, Ethiopia, from January 2019 to August 2019. The total sample size of the study was 284. The source populations were TB patients who have followed up for TB treatment at public health facilities of Addis Ababa. The sample size was allocated to the selected health facilities proportional to their size, and study subjects were enrolled to the study during the study period. Data were collected by a structured data sheet from the selected health center registration book. Data were entered into Epi Data software and analyzed by using SPSS version 20. Descriptive statistical methods were used to summarize the sociodemographic characteristics of the study participants. Survival curves were generated using the Kaplan-Meier method for all TB patients. RESULT: A total of 284 study participants were included in the study. It was found that 46.8% of the study population have undernutrition (BMI <18.5 kg/m2) at the time of registration for treatment. Out of undernourished patients, 54 (19.0%) had severe malnutrition and 78 (27.5%) had moderate undernutrition. At the end of the two-month intensive treatment period, the under nutrition prevalence declined to 38.7%. Of the 284 patients, 17 (6.0%) died before completing anti-TB treatment. Three quarters of all forms of TB deaths occurred within 57 days after the start of anti-TB treatment. The proportion of deaths by nutritional status at treatment initiation among normal, moderate acute malnutrition, and severe acute malnutrition TB patients was 3.1%, 8.9%, and 16.3%, respectively. CONCLUSION: Almost half of the TB patients were undernourished at the start of anti-TB treatment based on BMI. From the malnourished, less than 20% of the participants gained weight and moved to normal weight at the end of the two-month intensive treatment period. The high death rate was reported among severely malnourished tuberculosis patients, but it needs a larger study to further understand predictors. To enhance the increment of nutritional status during treatment, the government should give attention to support nutritional supplements for TB patients.