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.

Pulmonary tuberculosis case notification and burden of drug resistance among children under 15 years of age in Ethiopia: sub-analysis from third-round drug resistance tuberculosis survey.

INTRODUCTION: Data on the burden of bacteriologically confirmed childhood Tuberculosis (PTB) and drug-resistant TB in Ethiopia is limited due to difficulties related to its diagnosis in this population. Therefore, this study aimed to assess bacteriologically confirmed childhood PTB Case Notification Rates (CNRs) and the burden of Drug Resistant-Tuberculosis among children in Ethiopia. METHOD: Retrospective secondary clinical and laboratory data were obtained from 3rd round national DR-TB survey which was conducted between August 2017 and January 2019. We used IBM SPSS 24 for sub-analysis of 3rd round Drug Resistant-Tuberculosis data. Descriptive statistics were used in computing the association between the sociodemographic characteristics and PTB CNRs, and the strength of the associations was determined using binary logistic regression with Odds ratios (OR) with a 95% confidence interval (CI). RESULT: Overall, 102 bacteriologically confirmed childhood PTB cases were identified with a median age of 12 (range 1-14) years. Of these, 54 (52.9%) were females and 81 (79.4%) lived in rural areas. HIV-TB co-infection cases were 5/102 (4.3%) and the majority (98%) of cases were newly diagnosed children. Nationally, the incidence of bacteriologically confirmed childhood PTB was calculated to be 5.1 per 100,000 children. The burden of Drug Resistant-Tuberculosis to at least one of the five first-line anti-TB drugs tested was five (6.5%) cases and one (1.3%) was found to be a Multi-drug resistant tuberculosis case. Drug-resistant tuberculosis was significantly associated with the age group 10-14 years (P = 0.002; [AOR] 29.76; [95% CI, 3.51-252.64]) and children living in urban areas (P = 0.027; [AOR] 5.76; 95% CI, 1.22-27.09). CONCLUSION: Bacteriologically confirmed childhood PTB cases increased as the age of the children increased. Most of the bacteriologically confirmed childhood PTB and the identified drug Resistant-Tuberculosis cases were new cases. Also, rural children were more affected by TB than their urban, counterparts Drug Resistant-Tuberculosis was higher in urban resident children.

Prevalence of tuberculosis and associated factors among presumptive TB refugees residing in refugee camps in Ethiopia.

BACKGROUND: Tuberculosis (TB) causes significant morbidity and mortality in refugee populations. Although Ethiopia is the third largest refugee-hosting country in Africa, there is limited published data on the prevalence and associated factors of TB in refugees. The objective of this study was to estimate the prevalence of bacteriologically confirmed pulmonary TB (PTB) and explore associated factors in presumptive TB refugees residing in refugee camps in Ethiopia. METHODS: A facility-based cross-sectional study was conducted between February and August 2021 in refugee camps in Ethiopia. Data were collected consecutively from 610 presumptive TB refugees who attended for TB diagnosis in selected refugee camp clinics in Ethiopia. A pre-tested questionnaire was used to collect data, and sputum samples were collected from eligible study participants. The Xpert Mycobacterium tuberculosis (MTB)/Rifampicin (RIF) assay was performed on direct spot sputum samples, whereas morning sputum samples were processed and inoculated for bacteriological culture using Mycobacterium Growth Indicator Tube (MGIT) and Lowsteen Jensen (LJ) methods. The statistical software package (STATA version 14) was used for statistical analysis. A logistic regression model was used for the evaluation of the association between bacteriologically confirmed TB cases and the associated factors. Descriptive statistics were used for the expression of the results, and statistical significance was assumed at p < 0.05. RESULTS: Out of 610 study participants, more than half were female (54.9%), and the mean age was 37.9 years (SD, 16.64). The prevalence of bacteriologically confirmed PTB cases among refugees residing in refugee camps in Ethiopia was 13.3% (95% CI, 10.7-16.2%) using the Xpert MTB/RIF assay and/or culture. MTB was detected in 12.8% (95% CI, 10.2-15.7%) of the individuals using the Xpert MTB/RIF assay, while culture positivity was observed in 11.6% (95% CI, 9.2-14.5%). The multivariable logistic regression model showed South Sudan origins (adjusted odds ratio, AOR = 7.74; 95% CI, 3.05-19.64), age group, 19-38 years old (AOR = 5.66; 95% CI, 1.86-17.28), and male sex (AOR = 2.69; 95% CI, 1.58-4.56) were significantly associated with the bacteriologically confirmed TB among refugees residing in refugee camps in Ethiopia. CONCLUSION: The prevalence of bacteriologically confirmed PTB among presumptive TB refugees residing in refugee camps in Ethiopia was high. The national TB program should strengthen TB prevention and control activities in the refugee camps of Ethiopia. Moreover, an active TB survey program should be implemented in refugee camps in Ethiopia.

Epidemiology of extensively drug-resistant tuberculosis among patients with multidrug-resistant tuberculosis: A systematic review and meta-analysis.

OBJECTIVES: To estimate the pooled proportion of extensively drug-resistant tuberculosis (XDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) in patients with multidrug-resistant TB (MDR-TB). METHODS: We systematically searched articles from electronic databases: MEDLINE (PubMed), ScienceDirect, and Google Scholar. We also searched gray literature from the different literature sources main outcome of the review was either XDR-TB or pre-XDR-TB in patients with MDR-TB. We used the random-effects model, considering the substantial heterogeneity among studies. Heterogeneity was assessed by subgroup analyses. STATA version 14 was used for analysis. RESULTS: A total of 64 studies that reported on 12,711 patients with MDR-TB from 22 countries were retrieved. The pooled proportion of pre-XDR-TB was 26% (95% confidence interval [CI]: 22-31%), whereas XDR-TB in MDR-TB cases was 9% (95% CI: 7-11%) in patients treated for MDR-TB. The pooled proportion of resistance to fluoroquinolones was 27% (95% CI: 22-33%) and second-line injectable drugs was 11% (95% CI: 9-13%). Whereas the pooled resistance proportions to bedaquiline, clofazimine, delamanid, and linezolid were 5% (95% CI: 1-8%), 4% (95% CI: 0-10%), 5% (95% CI; 2-8%), and 4% (95% CI: 2-10%), respectively. CONCLUSION: The burden of pre-XDR-TB and XDR-TB in MDR-TB were considerable. The high burdens of pre-XDR-TB and XDR-TB in patients treated for MDR-TB suggests the need to strengthen TB programs and drug resistance surveillance.

Bacteriologically confirmed extrapulmonary tuberculosis and the associated risk factors among extrapulmonary tuberculosis suspected patients in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: The actual burden of bacteriologically confirmed extrapulmonary tuberculosis (EPTB) and risk factors in Ethiopia is not well known due to the lack of a strong surveillance system in Ethiopia. Thus, this study was conducted to estimate the pooled prevalence of bacteriologically confirmed EPTB and the associated risk factors among persons suspected to have non-respiratory tuberculosis in Ethiopia. METHODS: A systematic review and meta-analysis of published studies reporting the prevalence of EPTB from searched electronic databases; Science Direct, PubMed, and Google Scholar was estimated spread across the research periods, nationally, and in different areas, using a fixed-effects model. We used I2 to analyze heterogeneity in the reported prevalence of bacteriologically confirmed extrapulmonary tuberculosis. RESULTS: After reviewing 938 research articles, 20 studies (19 cross-sectional and 1 retrospective) from 2003 to 2021 were included in the final analyses. The pooled prevalence of bacteriologically confirmed EPTB was 43% (95%CI; 0.34-0.52, I2 = 98.45%). The asymmetry of the funnel plot revealed the presence of publication bias. Specifically the pooled prevalence of bacteriologically confirmed EPTB based on smear microscopy, Xpert MTB/RIF assay, and culture were 22% (95%CI; 0.13-0.30, I2 = 98.56%), 39% (95%CI; 0.23-0.54, I2 = 98.73%) and 49% (95%CI; 0.41-0.57, I2 = 96.43%) respectively. In this study, a history of pulmonary tuberculosis (PTB) contact with PTB patients, contact with live animals, consumption of raw milk, HIV-positive, male, and lower monthly income, were found to be independently associated with bacteriologically confirmed EPTB. CONCLUSION: Ethiopia has a high rate of bacteriologically confirmed EPTB. A history of previous PTB, being HIV-positive and having contact with PTB patients were the most reported risk factors for EPTB in the majority of studies. Strengthening laboratory services for EPTB diagnosis should be given priority to diagnose EPTB cases as early as possible.

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.

Drug resistance and its risk factors among extrapulmonary tuberculosis in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Drug-resistant tuberculosis and extrapulmonary tuberculosis are the world major public health issues. Although some primary studies have been reported on the burden of drug-resistant tuberculosis in extrapulmonary tuberculosis patients in Ethiopia, there is no systematic review and meta-analysis that attempt to summarize the available literature. Thus, we aimed to estimates the prevalence of drug-resistance in extrapulmonary tuberculosis patients and summarize the risk factors associated with the occurrence of extrapulmonary tuberculosis in Ethiopia. METHODS: We conducted a systematic review of the published primary studies on extrapulmonary drug-resistant tuberculosis in Ethiopia. RESULTS: Eight observational studies were included in this review from different regions of Ethiopia. The overall pooled prevalence of rifampicin resistance was 6% (95% CI 0.03-0.10), while isoniazid resistance was 7% (95% CI 0.03-0.12). The pooled prevalence of multidrug-resistant tuberculosis was 4% (95% CI 0.01-0.07). Previous tuberculosis treatment history and male gender are frequently reported risk factors for developing drug-resistant tuberculosis in extrapulmonary tuberculosis patients. CONCLUSION: The current review has identified a high proportion of resistance to rifampicin, isoniazid, and multidrug-resistant tuberculosis in patients with extrapulmonary tuberculosis in Ethiopia. Clinicians should request drug susceptibility testing for all patients with presumptive extrapulmonary tuberculosis to detect drug-resistance.

National treatment outcome and predictors of death and treatment failure in multidrug-resistant tuberculosis in Ethiopia: a 10-year retrospective cohort study.

OBJECTIVES: Treatment success rate in patients treated for multidrug-resistant tuberculosis (MDR-TB) is low, but predictors of treatment failure and death have been under-reported. Thus, we aimed to determine the national proportion of treatment success rate in the past 10 years and factors that predict treatment failure and death in patients with MDR-TB in Ethiopia. SETTING: A retrospective cohort study with a 10-years follow-up period was conducted in 42 MDR-TB treatment-initiating centres in Ethiopia. PARTICIPANTS: A total of 3395 adult patients with MDR-TB who had final treatment outcome and who were treated under national TB programme were included. Data were collected from clinical charts, registration books and laboratory reports. Competing risk survival analysis model with robust standard errors (SE) was used to determine the predictors of treatment failure and death. PRIMARY AND SECONDARY OUTCOMES: Treatment outcome was a primary outcome whereas predictors of treatment failure and death were a secondary outcome. RESULTS: The proportion of treatment success was 75.7%, death rate was 12.8%, treatment failure was 1.7% and lost to follow-up was 9.7%. The significant predictors of death were older age (adjusted hazard ratio (AHR)=1.03; 95% CI 1.03 to 1.05; p<0.001), HIV infection (AHR=2.0; 95% CI 1.6 to 2.4; p<0.001) and presence of any grade of anaemia (AHR=1.7; 95% CI 1.4 to 2.0; p<0.001). Unlike the predictors of death, all variables included into multivariable model were not significantly associated with treatment failure. CONCLUSION: In the past 10 years, although MDR-TB treatment success in Ethiopia has been consistently favourable, the proportion of patients who died is still considerable. Death could be attributed to advanced age, HIV infection and anaemia. Prospective cohort studies are necessary to further explore the potentially modifiable predictors of treatment failure.

Predictors of mortality in patients with drug-resistant tuberculosis: A systematic review and meta-analysis.

BACKGROUND: Even though the lives of millions have been saved in the past decades, the mortality rate in patients with drug-resistant tuberculosis is still high. Different factors are associated with this mortality. However, there is no comprehensive global report addressing these risk factors. This study aimed to determine the predictors of mortality using data generated at the global level. METHODS: We systematically searched five electronic major databases (PubMed/Medline, CINAHL, EMBASE, Scopus, Web of Science), and other sources (Google Scholar, Google). We used the Joanna Briggs Institute Critical Appraisal tools to assess the quality of included articles. Heterogeneity assessment was conducted using the forest plot and I2 heterogeneity test. Data were analyzed using STATA Version 15. The pooled hazard ratio, risk ratio, and odd's ratio were estimated along with their 95% CIs. RESULT: After reviewing 640 articles, 49 studies met the inclusion criteria and were included in the final analysis. The predictors of mortality were; being male (HR = 1.25,95%CI;1.08,1.41,I2;30.5%), older age (HR = 2.13, 95%CI;1.64,2.62,I2;59.0%,RR = 1.40,95%CI; 1.26, 1.53, I2; 48.4%) including a 1 year increase in age (HR = 1.01, 95%CI;1.00,1.03,I2;73.0%), undernutrition (HR = 1.62,95%CI;1.28,1.97,I2;87.2%, RR = 3.13, 95% CI; 2.17,4.09, I2;0.0%), presence of any type of co-morbidity (HR = 1.92,95%CI;1.50-2.33,I2;61.4%, RR = 1.61, 95%CI;1.29, 1.93,I2;0.0%), having diabetes (HR = 1.74, 95%CI; 1.24,2.24, I2;37.3%, RR = 1.60, 95%CI;1.13,2.07, I2;0.0%), HIV co-infection (HR = 2.15, 95%CI;1.69,2.61, I2; 48.2%, RR = 1.49, 95%CI;1.27,1.72, I2;19.5%), TB history (HR = 1.30,95%CI;1.06,1.54, I2;64.6%), previous second-line anti-TB treatment (HR = 2.52, 95% CI;2.15,2.88, I2;0.0%), being smear positive at the baseline (HR = 1.45, 95%CI;1.14,1.76, I2;49.2%, RR = 1.58,95%CI;1.46,1.69, I2;48.7%), having XDR-TB (HR = 2.01, 95%CI;1.50,2.52, I2;60.8%, RR = 2.44, 95%CI;2.16,2.73,I2;46.1%), and any type of clinical complication (HR = 2.98, 95%CI; 2.32, 3.64, I2; 69.9%). There are differences and overlaps of predictors of mortality across different drug-resistance categories. The common predictors of mortality among different drug-resistance categories include; older age, presence of any type of co-morbidity, and undernutrition. CONCLUSION: Different patient-related demographic (male sex, older age), and clinical factors (undernutrition, HIV co-infection, co-morbidity, diabetes, clinical complications, TB history, previous second-line anti-TB treatment, smear-positive TB, and XDR-TB) were the predictors of mortality in patients with drug-resistant tuberculosis. The findings would be an important input to the global community to take important measures.

Health care seeking behavior among presumptive tuberculosis patients in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Health seeking behavior is one of the challenges affecting tuberculosis (TB) control program because of its high risk to prolonged diseases transmission and poor treatment outcome. Although there are few primary studies that reported diversified magnitudes of health seeking behavior among presumptive TB patients in Ethiopia, there is no review study that attempted to summarize the available evidence. Thus, this review was aimed to estimate the proportion of health care seeking behavior from health facility and to summarize the reasons why individuals with presumptive TB are not seeking health care in Ethiopia. METHOD: A systematic review and meta-analysis study was conducted on primary studies that reported proportion of health seeking behavior among presumptive TB patients. Electronic databases: PubMed, Google Scholar and Science Direct were searched to retrieve studies published in English language from Ethiopia without restricting publication year. In addition, bibliographies of included studies were also screened to retrieve potential studies. The keywords "health seeking", "health seeking behavior", "TB suspects" and "presumptive TB" were used both in Medical Subject Heading (MeSH) and free text. Random effects meta-analysis model was used to estimate the pooled proportions of health care seeking and not seeking behaviors. Stata version 14 was used for data analysis. RESULT: Five studies which involved 3230 patients with presumptive TB were included into this review. The pooled estimated proportion of health care seeking behavior among presumptive TB patients from health facilities was 65% (95% CI, 54-76%), while the pooled proportion of not seeking health care from any sources was 17% (95% CI;6-27%). In addition, 18% (95% CI; 5-30%) of presumptive TB patients were seeking health care from inappropriate sources. Being female, younger age, low income status, absence of previous TB treatment history, low education status were the risk factors that associated with low health care seeking behavior. CONCLUSION: Considerable proportion of patients with presumptive TB were not seeking health care from health facilities or seeks care from inappropriate sources in Ethiopia. Implementing efforts that could improve health care seeking behavior is vital to prevent prolonged disease transmission through immediate treatment commencement.

High Inequality and Slow Services Improvement in Newborn and Child Health Interventions in Ethiopia.

BACKGROUND: In the previous years, efforts have been made to reduce the inequality gap in newborn and child health interventions in Ethiopia. However, there is still limited evidence on the extent and trends of inequality on newborn and child health interventions. Thus, we aimed to assess newborn and child health interventions, inequality levels, and trends during four demographic and health survey periods based on inequality dimensions: economic status, education level, residency, and child's sex in Ethiopia. METHODS: We conducted an inequality analysis on four periods (2000, 2005, 2011, and 2016) of the Ethiopian Demographic and Health Survey (EDHS) data. We estimated inequality related to economic and education status using percentage, relative concentration index, and slope index, while mean percentage difference and ratio were used to assess inequality due to residency and child's sex. RESULTS: The coverage of services was concentrated in the richest quintile, highly educated families, and urban dwellers. Child and newborn health intervention service coverage improvement in the past four survey periods was less than 10.0% for all services, and there is high disparity between sub-national regions. Full immunization-related inequality was highest in Ethiopia compared to four east-central African countries. CONCLUSION: Increasing service coverage and improving equitable access to routine immunizations could fill the existing inequality gap while focusing on the underserved group. In addition, strengthening regular monitoring processes is also vital to know those left behind.