Tuberculosis preventive treatment uptake among people living with HIV during COVID-19 period in Addis Ababa, Ethiopia: a retrospective data review.

BACKGROUND: Screening for tuberculosis (TB) and providing TB preventive treatment (TPT) along with antiretroviral therapy is key components of human immune deficiency virus (HIV) care. The uptake of TPT during the coronavirus disease 2019 (COVID-19) period has not been adequately assessed in Addis Ababa City Administration. This study aimed at assessing TPT uptake status among People living with HIV (PLHIV) newly initiated on antiretroviral therapy during the COVID-19 period at all public hospitals of Addis Ababa City Administration, Ethiopia. METHODS: A retrospective data review was conducted from April-July 2022. Routine District Health Information System 2 database was reviewed for the period from April 2020-March 2022. Proportion and mean with standard deviation were computed. Logistic regression analysis was conducted to assess factors associated with TPT completion. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 1,069 PLHIV, aged 18 years and above were newly initiated on antiretroviral therapy, and of these 1,059 (99.1%) underwent screening for TB symptoms. Nine hundred twelve (86.1%) were negative for TB symptoms. Overall, 78.8% (719) of cases who were negative for TB symptoms were initiated on TPT, and of these 70.5% and 22.8% were completed and discontinued TPT, respectively. Of 719 cases who were initiated on TPT, 334 (46.5%) and 385 (53.5%) were initiated on isoniazid plus rifapentine weekly for three months and Isoniazid preventive therapy daily for six months, respectively. PLHIV who were initiated on isoniazid plus rifapentine weekly for three months were more likely to complete TPT (adjusted odds ratio [AOR],1.68; 95% confidence interval [CI], 1.01, 2.79) compared to those who were initiated on Isoniazid preventive therapy daily for six months. CONCLUSION: While the proportion of PLHIV screened for TB was high, TPT uptake was low and far below the national target of achieving 90% TPT coverage. Overall a considerable proportion of cases discontinued TPT in this study. Further strengthening of the programmatic management of latent TB infection among PLHIV is needed. Therefore, efforts should be made by the Addis Ababa City Administration Health Bureau authorities and program managers to strengthen the initiation and completion of TPT among PLHIV in public hospitals.

Assessment of maternal and child health care services performance in the context of COVID-19 pandemic in Addis Ababa, Ethiopia: evidence from routine service data.

BACKGROUND: In many settings, health care service provision has been modified to managing COVID-19 cases, and this has been affecting the provision of maternal and child health services. The aim of this study was to assess trends in selected maternal and child health services performance in the context of COVID-19 pandemic. METHODS: A cross-sectional data review was conducted in Addis Ababa, Ethiopia from April to May 2021. Routine health management information system database was reviewed from Addis Ababa Health Bureau for the period from July 2019 to March 2021 across all quarters. Proportion and mean with standard deviation were computed. T-test was used to assess statistically significant differences in services mean performance. RESULTS: Postnatal care  visit, new contraceptives accepters, safe abortion care and number of under-5 years old children treated for pneumonia significantly decreased by 9.3% (p-value 0.04), 20.3% (p-value 0.004), 23.7% (p-value 0.01) and 77.2% (p-value < 0.001), respectively during the first 8 months of the COVID-19 pandemic compared to the previous 8 months' average performance. The trends in Antenatal care first visit, new contraceptive accepters, pentavalent-3 vaccination and under-five children treated for pneumonia began to decline in January to  March 2020, a quarter when the COVID-19 pandemic began; with accelerated declines in April to June 2020 following national lockdown. The trends for the stated services began to increase during July-September 2020, the last quarter of national lockdown. Contraceptive accepters and pentavalent-1 vaccination continued to decline and showed no recovery until January-March 2021 when this study was completed. CONCLUSIONS: Most of the maternal and child health services performance declined following the onset of COVID-19 pandemic and national lockdown, and most of the services began recovering during July-September 2020, the last quarter of national lockdown. However, new and repeat contraceptive accepters and pentavalent-1 recipients continue to decline and show no recovery during end of the study period. Implementing COVID-19 prevention measures and assuring the community about the safety of service delivery is imperative to ensure continuity of the maternal and child health services. Regular monitoring and evaluation of services performance is required to identify slowly recovering services and respond to potentially volatile changes during the COVID-19 pandemic.

Mapping time use in clinical trials for vaccines against emerging infectious diseases.

BACKGROUND: Vaccines are potent tools to prevent outbreaks of emerging infectious diseases from becoming epidemics and need to be developed at an accelerated pace to have any impact on the course of an ongoing epidemic. The aim of this study was to describe time use in the execution of vaccine trials, to identify steps that could be accelerated to improve preparedness and planning for future emerging infectious diseases vaccine trials. METHODS: We used a mixed-methods approach to map time use and process steps that could be accelerated during vaccine trials. Trials for vaccines against infectious diseases registered in three global trial databases reported in the period 2011-2017 were eligible to join the survey. We invited sponsors to contribute data through a predefined structured questionnaire for clinical trial process metrics. Data were stratified by trial phase, disease type (i.e. emerging infectious diseases or not emerging infectious diseases), sponsor type, and continent. Qualitative interviews were conducted with purposively selected sponsors, and thematic analysis of the interview transcripts was performed. RESULTS: Based on data from 155 vaccine trials including 29,071 subjects, 52% were phase I, 23% phase II, and 25% phase III. We found that the regulatory approval, subject enrollment, study execution, and study close-out accounted for most of the cycle time of the vaccine trial process. Cycle times for the regulatory and ethical approvals, contract agreement, site initiation, and study execution were shorter in trials conducted during outbreaks. Qualitative interviews indicated that early engagement of the regulatory and independent ethical committee authorities in planning the vaccine trials was critical for saving time in trial approval. Furthermore, adapting the trial implementation to the reality of the study sites and active involvement of the local investigators during the planning of the trial and protocol writing were stated to be of paramount importance to successful completion of trials at an accelerated pace. CONCLUSION: The regulatory approval, subject recruitment, study execution, and close-out cycle times accounted for most of the vaccine trial time use and are activities that could be accelerated during a vaccine trial planning and implementation. We encourage tracking of key cycle time metrics and facilitating sharing of knowledge across industry and academia, as this may serve to reduce the time from index case detection to access of a vaccine during emerging infectious diseases epidemics.

Lipid droplets and the transcriptome of Mycobacterium tuberculosis from direct sputa: a literature review.

Mycobacterium tuberculosis (Mtb), the main etiology of tuberculosis (TB), is predominantly an intracellular pathogen that has caused infection, disease and death in humans for centuries. Lipid droplets (LDs) are dynamic intracellular organelles that are found across the evolutionary tree of life. This review is an evaluation of the current state of knowledge regarding Mtb-LD formation and associated Mtb transcriptome directly from sputa.Based on the LD content, Mtb in sputum may be classified into three groups: LD positive, LD negative and LD borderline. However, the clinical and evolutionary importance of each state is not well elaborated. Mounting evidence supports the view that the presence of LD positive Mtb bacilli in sputum is a biomarker of slow growth, low energy state, towards lipid degradation, and drug tolerance. In Mtb, LD may serve as a source of chemical energy, scavenger of toxic compounds, prevent destruction of Mtb through autophagy, delay trafficking of lysosomes towards the phagosome, and contribute to Mtb persistence. It is suggest that LD is a key player in the induction of a spectrum of phenotypic and metabolic states of Mtb in the macrophage, granuloma and extracellular sputum microenvironment. Tuberculosis patients with high proportion of LD positive Mtb in pretreatment sputum was associated with higher rate of poor treatment outcome, indicating that LD may have a clinical application in predicting treatment outcome.The propensity for LD formation among Mtb lineages is largely unknown. The role of LD on Mtb transmission and disease phenotype (pulmonary TB vs extra-pulmonary TB) is not well understood. Thus, further studies are needed to understand the relationships between LD positivity and Mtb lineage, Mtb transmission and clinical types.

Correction to: Developing vaccines against epidemic-prone emerging infectious diseases.

In the original publication of this article, the author name Richard Hatchett was incorrectly published.

Developing vaccines against epidemic-prone emerging infectious diseases.

Today's world is characterized by increasing population density, human mobility, urbanization, and climate and ecological change. This global dynamic has various effects, including the increased appearance of emerging infectious diseases (EIDs), which pose a growing threat to global health security.Outbreaks of EIDs, like the 2013-2016 Ebola outbreak in West Africa or the current Ebola outbreak in Democratic Republic of the Congo (DRC), have not only put populations in low- and middle-income countries (LMIC) at risk in terms of morbidity and mortality, but they also have had a significant impact on economic growth in affected regions and beyond.The Coalition for Epidemic Preparedness Innovation (CEPI) is an innovative global partnership between public, private, philanthropic, and civil society organizations that was launched as the result of a consensus that a coordinated, international, and intergovernmental plan was needed to develop and deploy new vaccines to prevent future epidemics.CEPI is focusing on supporting candidate vaccines against the World Health Organization (WHO) Blueprint priority pathogens MERS-CoV, Nipah virus, Lassa fever virus, and Rift Valley fever virus, as well as Chikungunya virus, which is on the WHO watch list. The current vaccine portfolio contains a wide variety of technologies, ranging across recombinant viral vectors, nucleic acids, and recombinant proteins. To support and accelerate vaccine development, CEPI will also support science projects related to the development of biological standards and assays, animal models, epidemiological studies, and diagnostics, as well as build capacities for future clinical trials in risk-prone contexts.

Tuberculosis infectious pool and associated factors in East Gojjam Zone, Northwest Ethiopia.

BACKGROUND: Globally, tuberculosis (TB) lasts a major public health concern. Using feasible strategies to estimate TB infectious periods is crucial. The aim of this study was to determine the magnitude of TB infectious period and associated factors in East Gojjam zone. METHODS: An institution-based prospective study was conducted among 348 pulmonary TB (PTB) cases between December 2017 and December 2018. TB cases were recruited from all health facilities located in Hulet Eju Enesie, Enebse Sarmider, Debay Tilatgen, Dejen, Debre-Markos town administration, and Machakel districts. Data were collected through an exit interview using a structured questionnaire and analyzed by IBM SPSS version25. The TB infectious period of each patient category was determined using the TB management time and sputum smear conversion time. The sum of the infectious period of each patient category gave the infectious pool of the study area. A multivariable logistic regression analysis was used to identify factors associated with the magnitude of TB infectious period. RESULTS: Of the total participated PTB cases, 209(60%) were male, 226(65%) aged < 30 years, 205(59%) were from the rural settings, and 77 (22%) had comorbidities. The magnitude of the TB infectious pool in the study area was 78,031 infectious person-days. The undiagnosed TB cases (44,895 days), smear-positive (14,625 days) and smear-negative (12,995 days) were major contributors to the infectious pool. The overall average median TB management time was 142.4 days (IQR, 98-238 days). Similarly, the average sputum smear conversion time of PTB cases (new and repeat) was 46 days. Residence, knowledge, form of TB, smoking, alcohol history, distance from the facility, comorbidity history and stigma were statistically significant factors TB infectious period (p-value< 0.05). CONCLUSIONS: The magnitude of the TB infectious pool is high even if it is lower than the findings of previous studies. This might be an indicator of poor access to TB services, service delays, low community awareness, impaired facility readiness, and poor transportation. Improving personal awareness and behavior, timely management of commodities, and using the TB management time in TB control are crucial to improving TB control activities.

Nε- and O-Acetylation in Mycobacterium tuberculosis Lineage 7 and Lineage 4 Strains: Proteins Involved in Bioenergetics, Virulence, and Antimicrobial Resistance Are Acetylated.

Increasing evidence demonstrates that lysine acetylation is involved in Mycobacterium tuberculosis (Mtb) virulence and pathogenesis. However, previous investigations in Mtb have only monitored acetylation at lysine residues using selected reference strains. We analyzed the global Nε- and O-acetylation of three Mtb isolates: two lineage 7 clinical isolates and the lineage 4 H37Rv reference strain. Quantitative acetylome analysis resulted in identification of 2490 class-I acetylation sites, 2349 O-acetylation and 141 Nε-acetylation sites, derived from 953 unique proteins. Mtb O-acetylation was thereby significantly more abundant than Nε-acetylation. The acetylated proteins were found to be involved in central metabolism, translation, stress responses, and antimicrobial drug resistance. Notably, 261 acetylation sites on 165 proteins were differentially regulated between lineage 7 and lineage 4 strains. A total of 257 acetylation sites on 161 proteins were hypoacetylated in lineage 7 strains. These proteins are involved in Mtb growth, virulence, bioenergetics, host-pathogen interactions, and stress responses. This study provides the first global analysis of O-acetylated proteins in Mtb. This quantitative acetylome data expand the current understanding regarding the nature and diversity of acetylated proteins in Mtb and open a new avenue of research for exploring the role of protein acetylation in Mtb physiology.

Patients' and health system's delays in the diagnosis and treatment of new pulmonary tuberculosis patients in West Gojjam Zone, Northwest Ethiopia: a cross-sectional study.

BACKGROUND: Tuberculosis (TB) is a major public health concern in the developing world. Early diagnosis and prompt initiation of treatment is essential for effective TB control. The aim of this study was to determine the length and analyze associated factors of patients' and health system's delays in the diagnosis and treatment of new pulmonary TB (PTB) patients. METHODS: A cross-sectional study was conducted in 30 randomly selected public health facilities in West Gojjam Zone, Amhara Region, Ethiopia. Newly diagnosed PTB patients who were ≥15 years of age were consecutively enrolled in the study. Patients' delay (the time period from onset of TB symptoms to first presentation to a formal health provider) and health system's delay (the time period from first presentation to a formal health provider to first start of TB treatment) were measured. Median patients' and health system's delays were calculated. Mixed effect logistic regression was used to analyze predictors of patients' and health system's delays. RESULTS: Seven hundred six patients were enrolled in the study. The median patients' delay was 18 days (interquartile range [IQR]: 8-34 days) and the median health system's delay was 22 days (IQR: 4-88 days). Poor knowledge of TB (adjusted odds ratio [AOR], 2.33; 95 % confidence interval [CI], 1.34-4.05), first visit to non-formal health provider (AOR, 47.56; 95 % CI, 26.31-85.99), self-treatment (AOR, 10.11; 95 % CI, 4.53-22.56) and patients' age (≥45 years) (AOR, 2.99; 95 % CI, 1.14-7.81) were independent predictors of patients' delay. Smear-negative TB (AOR, 1.88; 95 % CI, 1.32-2.68) and first visit to public health centers (AOR, 2.22; 95 % CI, 1.52-3.25) and health posts (AOR, 5.86; 95 % CI, 1.40-24.39) were found to be independent predictors of health system's delay. CONCLUSIONS: The health system's delay in this study was long and contributed more than 50 % of the total delay. Better TB diagnostic tools to complement sputum smear microscopy are needed to early diagnose PTB cases at peripheral health facilities. In addition, due emphasis should be given to increase public awareness about symptoms and consequences of TB disease.

Assessment of health system challenges and opportunities for possible integration of diabetes mellitus and tuberculosis services in South-Eastern Amhara Region, Ethiopia: a qualitative study.

BACKGROUND: The double burden of tuberculosis (TB) and diabetes mellitus (DM) is a significant public health problem in low and middle income countries. However, despite the known synergy between the two disease conditions, services for TB and DM have separately been provided. The objective of this study was to explore health system challenges and opportunities for possible integration of DM and TB services. METHODS: This was a descriptive qualitative study which was conducted in South-Eastern Amhara Region, Ethiopia. Study participants included health workers (HWs), program managers and other stakeholders involved in TB and DM prevention and control activities. Purposive sampling was applied to select respondents. In order to capture diversity of opinions among participants, maximum variation sampling strategy was applied in the recruitment of study subjects. Data were collected by conducting four focus group discussions and 12 in-depth interviews. Collected data were transcribed verbatim and were thematically analyzed using NVivo 10 software program. RESULT: A total of 44 (12 in-depth interviews and 32 focus group discussion) participants were included in the study. The study participants identified a number of health system challenges and opportunities affecting the integration of TB-DM services. The main themes identified were: 1. Unavailability of system for continuity of DM care. 2. Inadequate knowledge and skills of health workers. 3. Frequent stockouts of DM supplies. 4. Patient's inability to pay for DM services. 5. Poor DM data management. 6. Less attention given to DM care. 7. Presence of a well-established TB control program up to the community level. 8. High level of interest and readiness among HWs, program managers and leaders at different levels of the health care delivery system. CONCLUSION: The study provided insights into potential health systems challenges and opportunities that need to be considered in the integration of TB-DM services. Piloting TB and DM integrated services in selected HFs of the study area is needed to assess feasibility for possible full scale integration of services for the two comorbid conditions.

Rapid diagnostic test: a critical need for outbreak preparedness and response for high priority pathogens.

Rapid diagnostic tests (RDTs) are critical for preparedness and response against an outbreak or pandemic and have been highlighted in the 100 Days Mission, a global initiative that aims to prepare the world for the next epidemic/pandemic by driving the development of diagnostics, vaccines and therapeutics within 100 days of recognition of a novel Disease X threat.RDTs play a pivotal role in early case identification, surveillance and case management, and are critical for initiating deployment of vaccine and monoclonal antibodies. Currently available RDTs, however, have limited clinical sensitivity and specificity and inadequate validation. The development, validation and implementation of RDTs require adequate and sustained financing from both public and private sources. While the World Health Assembly recently passed a resolution on diagnostic capacity strengthening that urges individual Member States to commit resources towards this, the resolution is not binding and implementation will likely be impeded by limited financial resources and other competing priorities, particularly in low-income countries. Meanwhile, the diagnostic industry has not sufficiently invested in RDT development for high priority pathogens.Currently, vaccine development projects are getting the largest funding support among medical countermeasures. Yet vaccines are insufficient tools in isolation, and pandemic preparedness will be incomplete without parallel investment in diagnostics and therapeutics.The Pandemic Fund, a global financing mechanism recently established for strengthening pandemic prevention, preparedness and response, may be a future avenue for supporting diagnostic development.In this paper, we discuss why RDTs are critical for preparedness and response. We also discuss RDT investment challenges and reflect on the way forward.

Total delay and associated factors among tuberculosis patients in Jimma Zone, Southwest Ethiopia.

BACKGROUND: Delays in diagnosis and treatment of tuberculosis (TB) increases severity of illness and continued transmission of TB in the community. Understanding the magnitude and factors associated with total delay is imperative to expedite case detection and treatment of TB. The aim of this study was to determine the length and analyze factors associated with total delay. METHODS: Analytic cross-sectional study was conducted in Jimma Zone, Southwest Ethiopia. All newly diagnosed TB patients > 15 years of age were included from randomly selected eight districts and one town in the study area. A structured questionnaire was applied to collect socio-demographic and clinical data. The median total delay was used to dichotomize the sample into delayed and non-delayed patient categories. Logistic regression analysis was used to analyse the association between independent and outcome variables. A p-value < 0.05 were considered statistically significant. RESULTS: A total of 1,161 patients were included in this study. The median total delay was 35 days. Patients who had swelling or wound in the neck region were more likely to be delayed than their counterpart [adjusted odds ratio (AOR) = 3.02, 95% confidence interval (CI): 1.62, 5.62]. Women were more likely to experience longer total delay (AOR = 1.46, 95% CI:1.00, 2.14) compared to men. Patients who had poor knowledge of TB were more likely to be delayed compared to those who had good knowledge (AOR = 3.92, 95% CI: 2.65, 5.80). CONCLUSION: The present study showed long total delay in diagnosis and treatment of TB. Targeted interventions that enhance TB knowledge and practice, expedite early suspect identification, referral and management of all forms of TB is imperative to reduce total delay in diagnosis and treatment of TB.

Availability and use of Standards in vaccine development.

Reference materials are critical in assay development for calibrating and assessing their suitability. The devasting nature of the COVID-19 pandemic and subsequent proliferation of vaccine platforms and technologies has meant that there is even a greater need for standards for immunoassay development, which are critical to assess and compare vaccines' responses. Equally important are the standards needed to control the vaccine manufacturing processes. Standardized vaccine characterization assays throughout process development are essential for a successful Chemistry, Manufacturing and Controls (CMC) strategy. In this perspective paper, we advocate for reference material incorporation into assays and their calibration to International Standards from preclinical vaccine development through control testing and provide insight into why this is necessary. We also provide information on the availability of WHO international antibody standards for CEPI-priority pathogens.

Proteome Profiling of Mycobacterium tuberculosis Cells Exposed to Nitrosative Stress.

Reactive nitrogen species (RNS) are secreted by human cells in response to infection by Mycobacterium tuberculosis (Mtb). Although RNS can kill Mtb under some circumstances, Mtb can adapt and survive in the presence of RNS by a process that involves modulation of gene expression. Previous studies focused primarily on stress-related changes in the Mtb transcriptome. This study unveils changes in the Mtb proteome in response to a sub-lethal dose of nitric oxide (NO) over several hours of exposure. Proteins were identified using liquid chromatography coupled with electrospray ionization mass spectrometry (LC-MS/MS). A total of 2911 Mtb proteins were identified, of which 581 were differentially abundant (DA) after exposure to NO in at least one of the four time points (30 min, 2 h, 6 h, and 20 h). The proteomic response to NO was marked by two phases, with few DA proteins in the early phase and a multitude of DA proteins in the later phase. The efflux pump Rv1687 stood out as being the only protein more abundant at all the time points and might play a role in the early protection of Mtb against nitrosative stress. These changes appeared to be compensatory in nature, contributing to iron homeostasis, energy metabolism, and other stress responses. This study thereby provides new insights into the response of Mtb to NO at the level of proteomics.

Spatial-temporal clustering of notified pulmonary tuberculosis and its predictors in East Gojjam Zone, Northwest Ethiopia.

BACKGROUND: Tuberculosis (TB) remains a key health menace in Ethiopia and its districts. This study aimed to assess the spatial-temporal clustering of notified pulmonary TB (PTB) cases in East Gojjam Zone, Northwest Ethiopia. METHODS: A retrospective study was conducted among all PTB cases reported from 2013-2019. Case notification rates (CNRs) of PTB cases at Kebele (the lowest administrative unit), woreda, and zone levels were estimated. The PTB clustering was done using global Moran's I statistics on Arc GIS 10.6. We used Kulldorff SaTScan 9.6 with a discrete Poisson model to identify statistically significant spatial-temporal clustering of PTB cases at Kebele level. Similarly, a negative binomial regression analysis was used to identify factors associated with the incidence of PTB cases at kebele level. RESULTS: A total of 5340 (52%) smear-positive and 4928 (48%) smear-negative PTB cases were analyzed. The overall mean CNR of PTB cases at zone, woreda and Kebele levels were 58(47-69), 82(56-204), and 69(36-347) per 100,000 population, respectively. The purely spatial cluster analysis identified eight most likely clusters (one for overall and one per year for seven reporting years) and 47 secondary clusters. Similarly, the space-time scan analysis identified one most likely and seven secondary clusters. The purely temporal analysis also detected one most likely cluster from 2013-2015. Rural residence, distance from the nearest health facility, and poor TB service readiness were factors (p-value <0.05) to PTB incidence at kebele level. CONCLUSION: The distribution of PTB cases was clustered. The PTB CNR was low and showed a decreasing trend during the reporting periods. Rural residence, distance from the health facilities, and poor facility readiness were factors of PTB incidence. Improving accessibility and readiness of health facilities mainly to rural and hotspot areas is vital to increase case detection and reduce TB transmission.

Treatment outcomes of patients with drug-sensitive tuberculosis under community-based versus facility-based directly observed treatment, short course strategy in Southwest Ethiopia: a prospective cohort study.

OBJECTIVE: To compare tuberculosis (TB) treatment outcomes and associated factors among patients attending community-based versus facility-based directly observed treatment, short course (DOTS). DESIGN: A prospective cohort study. SETTING: The study was conducted in Southwest Ethiopia. There were seven hospitals (five primary, one general and one specialised), 120 health centres and 494 health posts. PARTICIPANTS: A total of 1161 individuals consented to participate in the study (387 patients under community-based DOTS (CB-DOTS) and 774 patients under facility-based DOTS (FB-DOTS)). Individuals who could not respond to the questions, mentally or critically ill patients, and those less than 15 years old, were excluded from the study. PRIMARY OUTCOME MEASURE: TB treatment outcomes were compared among patients under CB-DOTS versus FB-DOTS. Risk ratio (RR), risk difference (RD) and confidence interval (CI) were calculated among the study groups. In addition, χ2 or Fisher's exact tests were used to compare group differences, with a p value of <0.05 considered statistically significant. RESULTS: Patients who opted for CB-DOTS were more likely to be cured by 12% than those who opted for FB-DOTS (RR=1.12, 95% CI=0.96 to 1.30). Patients under CB-DOTS had a lesser risk of death (RR=0.93, 95% CI=0.49 to 1.77) and a lower risk of treatment failure (RR=0.86, 95% CI=0.22 to 3.30) than those under FB-DOTS. Furthermore, patients who opted for CB-DOTS were less likely to have a positive sputum smear result at the end of the treatment period (p=0.042) compared with their counterparts. CONCLUSION: The study showed that CB-DOTS is more effective than FB-DOTS in terms of improving cure rate and sputum conversion rate, as well as lowering treatment failure rate. Our findings show the need for scaling up and a further decentralisation of CB-DOTS approach to improve access to TB treatment service for the rural community.

Pragmatic Management of Drug-Resistant Tuberculosis: A Qualitative Analysis of Human Resource Constraints in a Resource-Limited Country context-Ethiopia.

Objectives: Existing evidence suggests that drug-resistant tuberculosis (DR-TB) remains a huge public health threat in high-burden TB countries such as Ethiopia. The purpose of this qualitative study was to explore the challenges of healthcare workers (HCWs) involved in providing DR-TB care in Addis Ababa, Ethiopia. Methods: We conducted in-depth interviews with 18 HCWs purposively selected from 10 healthcare facilities in Addis Ababa, Ethiopia. We then transcribed the audiotaped interviews, and thematically analysed the transcripts using Braun and Clark's reflexive thematic analysis framework. Results: We identified five major themes: 1) inadequate training and provision of information on DR-TB to HCWs assigned to work in DR-TB services, 2) fear of DR-TB infection, 3) risk of contracting DR-TB, 4) a heavy workload, and 5) resource limitations. Conclusion: Our findings highlight major human resource constraints that current DR-TB care policies need to foresee and accommodate. New evidence and best practices on what works in DR-TB care in such resource-limited countries are needed in order to address implementation gaps and to meet global TB strategies.

Whole Genome Sequencing of Drug Resistant and Drug Susceptible Mycobacterium tuberculosis Isolates From Tigray Region, Ethiopia.

Background: Tuberculosis, mainly caused by Mycobacterium tuberculosis (Mtb), is an ancient human disease that gravely affects millions of people annually. We wanted to explore the genetic diversity and lineage-specific association of Mtb with drug resistance among pulmonary tuberculosis patients. Methods: Sputum samples were collected from pulmonary tuberculosis patients at six different healthcare institutions in Tigray, Ethiopia, between July 2018 and August 2019. DNA was extracted from 74 Mtb complex isolates for whole-genome sequencing (WGS). All genomes were typed and screened for mutations with known associations with antimicrobial resistance using in silico methods, and results were cross-verified with wet lab methods. Results: Lineage (L) 4 (55.8%) was predominant, followed by L3 (41.2%); L1 (1.5%) and L2 (1.5%) occurred rarely. The most frequently detected sublineage was CAS (38.2%), followed by Ural (29.4%), and Haarlem (11.8%). The recent transmission index (RTI) was relatively low. L4 and Ural strains were more resistant than the other strains to any anti-TB drug (P < 0.05). The most frequent mutations to RIF, INH, EMB, SM, PZA, ETH, FLQs, and 2nd-line injectable drugs occurred at rpoB S450L, katG S315T, embB M306I/V, rpsL K43R, pncA V139A, ethA M1R, gyrA D94G, and rrs A1401G, respectively. Disputed rpoB mutations were also shown in four (16%) of RIF-resistant isolates. Conclusion: Our WGS analysis revealed the presence of diverse Mtb genotypes. The presence of a significant proportion of disputed rpoB mutations highlighted the need to establish a WGS facility at the regional level to monitor drug-resistant mutations. This will help control the transmission of DR-TB and ultimately contribute to the attainment of 100% DST coverage for TB patients as per the End TB strategy.

Frequency and patterns of first- and second-line drug resistance-conferring mutations in Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in a cross-sectional study in Tigray Region, Ethiopia.

OBJECTIVES: Tuberculosis (TB) is a preventable and treatable infectious disease, but the continuing emergence and spread of multidrug-resistant TB is threatening global TB control efforts. This study aimed to describe the frequency and patterns of drug resistance-conferring mutations of Mycobacterium tuberculosis (MTB) isolates detected from pulmonary TB patients in Tigray Region, Ethiopia. METHODS: A cross-sectional study design was employed to collect sputum samples from pulmonary TB patients between July 2018 to August 2019. Culture and identification tests were done at Tigray Health Research Institute (THRI). Mutations conferring rifampicin (RIF), isoniazid (INH) and fluoroquinolone (FQ) resistance were determined in 227 MTB isolates using GenoType MTBDRplus and GenoType MTBDRsl. RESULTS: Mutations conferring resistance to RIF, INH and FQs were detected in 40/227 (17.6%), 41/227 (18.1%) and 2/38 (5.3%) MTB isolates, respectively. The majority of mutations for RIF, INH and FQs occurred at codons rpoB S531L (70%), katG S315T (78%) and gyrA D94Y/N (100%), respectively. This study revealed a significant number of unknown mutations in the rpoB, katG and inhA genes. CONCLUSION: High rates of mutations conferring resistance to RIF, INH and FQs were observed in this study. A large number of isolates showed unknown mutations, which require further DNA sequencing analysis. Periodic drug resistance surveillance and scaling-up of drug resistance testing facilities are imperative to prevent the transmission of drug-resistant TB in the community.

Correction: Characteristics of pulmonary multidrug-resistant tuberculosis patients in Tigray Region, Ethiopia: A cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0236362.].