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Mulusew Andualem Asemahagn,1 Getu Degu Alene,1 Solomon Abebe Yimer2,3 1School of Public Health, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia; 2Department of Microbiology, Unit for Genome Dynamics, Faculty of Medicine, University of Oslo, Oslo, Norway; 3Coalition for Epidemic Preparedness Innovations (CEPI), Oslo, NorwayCorrespondence: Mulusew Andualem Asemahagn Email muler.hi@gmail.comBackground: Tuberculosis (TB) remains a foremost global public health threat. Active TB control needs geographically accessible health facilities that have quality diagnostics, equipment, supplies, medicines, and staff.Objective: This study aimed at assessing the geographic distribution, physical accessibility, readiness and barriers of health facilities for TB services in East Gojjam zone, Ethiopia.Methods: A convergent parallel design was applied using health facility and geographic data. Data on facility attributes, service availability and readiness were collected by inteviewing TB officers, laboratory heads and onsite facility visits. Coordinates of health facilities and kebele centroids were collected by GPS. We used ArcGIS 10.6 to measure Euclidean distance from each kebele centroids to the nearest health facility. Descriptive statistics were computed by using SPSS version 25. Barriers to TB service readiness were explored by in-depth interviews. NVivo12 was used to thematically analyze the qualitative data.Results: The overall TB health service coverage (THSC) was 23% (ranging: 10– 85%). The mean distance from the nearest health facility was 8km (ranging: 0.5– 16km). About 132 (32%) kebeles had poor geographic accessibility to TB services (over 10km distance from the nearest health facility) and had poor facility readiness. Although 114 (95%) health facilities offered at least one TB service, 44 (38.6%) of them had no sputum smear microscopy. The overall TB readiness index was 63.5%: first-line anti-TB drugs (97%), diagnostics (63%), trained staffs, diagnostic and treatment guidelines (53%) and laboratory supplies (41%). Lack of health workers (laboratory personnel), inadequate budget, poor management practice and TB program support, inadequate TB commodity suppliers, and less accessible geographic locations of health facilities were identified as barriers to TB service readiness distribution.Conclusion: Considerable proportion of the population in the study area have poor access to quality TB diagnostic services due to low THSC and poor facility readiness. Barriers to TB service availability and readiness were health system related. Regular refresher training of health workers on TB, creating mechanisms to attract laboratory personnel to work in the study area and scaling up of sputum smear microscopy services, establishing an efficient mechanism for procurement, distribution, utilization and reporting of TB commodity supplies, and good management practices are crucial to enhance TB service readiness in the study zone.Keywords: tuberculosis, accessibility, readiness, barriers, health facilities, TB services, East Gojjam Zone, Ethiopia

Background: Tuberculosis (TB) is a major public health challenge in Ethiopia. TB treatment outcomes were suboptimal compared to the expected target of the national TB control Program. The provision of standard anti-TB treatment is the primary component of the directly observed treatment, short-course strategy. The aim of this study was to assess the TB treatment outcomes and the determinants of an unfavorable treatment outcome. The study used a cross-sectional study design at baseline and record review to identify treatment outcomes. A total of 1,161 TB patients were recruited from eight randomly selected districts and one town administration in the Jimma Zone, Ethiopia. Treatment outcomes were grouped into favorable and unfavorable. Of the total participants, 86.9% had a favorable treatment outcome, and 5.7% an unfavorable treatment outcome. The rest were transferred out and not recorded cases. Women were more likely to experience an unfavorable treatment outcome [adjusted odds ratio (AOR) = 1.96, 95% CI 1.06, 3.64]. Patients who were perceived to not be stigmatized were less likely to have an unfavorable treatment outcome (AOR = 0.32, 95% CI 0.15, 0.73). Patients who had a monthly income of > 3,500 Ethiopian birr were less likely to have an unfavorable outcome than patients who did not have a regular income (AOR = 0.04, 95% CI 0.01, 0.45). The observed treatment success rate is lower than the World Health Organization's target of successfully treating > 90% of detected TB cases. It is imperative to ensure that information, education and communication/behavior change communication strategies consider the needs of women and patients with perceived TB stigma. Furthermore, designing locally acceptable and affordable interventions may help to address the financial challenges of TB treatment adherence., Competing Interests: Supplementary Information. Ethics approval and consent to participate: Ethical Approval was obtained from the Regional Committee for Medical Research Ethics (REK Øst), Norway with the reference number 2015/2124 REK sør-øst B, and from the Institutional Review Board of Jimma University, Ethiopia, with the reference number RPGC/389/2016. Written (oral for the illiterate) informed consent was secured from each study participant before starting the data collection. For participants aged 15–17 years, informed consent was obtained from their parents or legal guardians and assent was obtained from the study participants. The collected data were stored in a locked cabinet (hard copy) and a computer file with a password (soft copy). Moreover, we confirm that all methods were carried out in accordance with relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Hepatic pregnancy, an exceedingly rare subtype of abdominal ectopic pregnancy, remains clinically challenging due to its infrequency, diverse presentations, and diagnostic difficulties. We report the clinical course, diagnostic journey and treatment of a woman with a primary hepatic pregnancy. The patient presented with acute pain in the right hypochondrium and vomiting. Imaging revealed a peripheral hypodense gestational sac within the right hepatic lobe containing a fetus with heart pulsations, as well as peritoneal fluid and pelvic collection. Following administration of mifepristone, the patient underwent a laparotomy, and expelled a developed fetus. Hepatic resection utilizing the Pringle maneuver was performed, and methotrexate was administered postoperatively. The patient had a stable recovery and vital signs and was discharged two days after surgery. This case highlights the diagnostic and management challenges of hepatic pregnancy, and emphasizes the need for heightened clinical suspicion and thorough evaluation. By sharing the experience, we aim to contribute insights to guide the diagnosis and management of similar cases., (© 2024 The Authors.)

Background: Schistosomiasis, officially named as a neglected tropical disease by The World Health Organization, is a serious parasitic disease caused by trematode flukes of the genus Schistosoma . It is a common infectious disease, endemic in more than 78 countries. The disease can involve various organs and poses far-reaching public health challenges., Case Summary: Here, we present a series of five patients with variable presentations: an asymptomatic patient who was diagnosed with colonic schistosomiasis upon screening colonoscopy; 2 patients with clinical suspicion of colonic cancer; and 2 patients with a clinical diagnosis of inflammatory bowel disease. All patients were subsequently confirmed to have colonic schistosomiasis after colonoscopy and histopathologic examination. The clinical manifestations, colonoscopy features and histologic findings of the patients are described. Most of the patients showed significant clinical improvement following administration of oral praziquantel., Conclusion: Intestinal schistosomiasis can present with features mimicking other gastrointestinal conditions. This disease should be a diagnostic consideration in patients who live in or have traveled to endemic areas., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., (© 2024. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ereso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

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, rps L K43R, pncA V139A, ethA M1R, gyr A 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Welekidan, Yimer, Skjerve, Dejene, Homberset, Tønjum and Brynildsrud.)

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., (© 2021. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mussie, Gradmann, Yimer and Manyazewal.)

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, χ 2 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

Tuberculosis (TB) remains to be the leading cause of morbidity and mortality in the developing world. Early TB case detection (TCD) and treatment of infectious cases is vital to reduce the TB burden. The objective of this study was to identify possible barriers to TCD in East Gojjam Zone, northwest Ethiopia. The study used a descriptive phenomenological research method. The study participants included 21 TB patients, six TB control officers, and 40 health workers (HWs) selected by a heterogeneous purposive sampling technique. In-depth interviews and focus group discussions were used to collect data. Interviews were audio recorded, transcribed verbatim, translated, and thematically analyzed using NVivo 12 software (developed by QSR International Qualitative Software Developer, Melbourne, Australia). The study participants identified numerous barriers to TCD which were grouped into three major themes and 14 subthemes: 1) patient-related barriers including rural residence, low income, poor health literacy, and health-seeking delay; 2) healthcare system barriers grouped into two subthemes: HWs barriers (shortage of HWs, lack of training access, and low level of knowledge and skills) and health facility barriers (health service delay, using only passive TCD strategy, poor health education provision, and lack of regular supervision and timely feedback); 3) sociocultural and environmental barriers which included stigma and discrimination, lack of health information sources, poor transportation infrastructure, and community resistance. In conclusion, the TCD activity which is one of the pillars of the TB control program has been confronted with several patient-related, environmental, and healthcare system-related barriers. Improving community health literacy, scale-up access, and improving quality of TB diagnostic services, conducting regular supportive supervision and provision of timely feedback, arranging regular refresher training and staff motivation and recruitment schemes, and engaging local health officials and political leaders to address budgetary problems for TB and transportation infrastructure challenges are imperative interventions to enhance the TCD efforts in the study area.

Despite the discovery of the tubercle bacillus more than 130 years ago, its physiology and the mechanisms of virulence are still not fully understood. A comprehensive analysis of the proteomes of members of the human-adapted Mycobacterium tuberculosis complex (MTBC) lineages 3, 4, 5, and 7 was conducted to better understand the evolution of virulence and other physiological characteristics. Unique and shared proteomic signatures in these modern, pre-modern and ancient MTBC lineages, as deduced from quantitative bioinformatics analyses of high-resolution mass spectrometry data, were delineated. The main proteomic findings were verified by using immunoblotting. In addition, analysis of multiple genome alignment of members of the same lineages was performed. Label-free peptide quantification of whole cells from MTBC lineages 3, 4, 5, and 7 yielded a total of 38,346 unique peptides derived from 3092 proteins, representing 77% coverage of the predicted proteome. MTBC lineage-specific differential expression was observed for 539 proteins. Lineage 7 exhibited a markedly reduced abundance of proteins involved in DNA repair, type VII ESX-3 and ESX-1 secretion systems, lipid metabolism and inorganic phosphate uptake, and an increased abundance of proteins involved in alternative pathways of the TCA cycle and the CRISPR-Cas system as compared to the other lineages. Lineages 3 and 4 exhibited a higher abundance of proteins involved in virulence, DNA repair, drug resistance and other metabolic pathways. The high throughput analysis of the MTBC proteome by super-resolution mass spectrometry provided an insight into the differential expression of proteins between MTBC lineages 3, 4, 5, and 7 that may explain the slow growth and reduced virulence, metabolic flexibility, and the ability to survive under adverse growth conditions of lineage 7., (Copyright © 2020 Yimer, Kalayou, Homberset, Birhanu, Riaz, Zegeye, Lutter, Abebe, Holm-Hansen, Aseffa and Tønjum.)

Background: Tuberculosis (TB) is among the top 10 causes of mortality and the first killer among infectious diseases worldwide. One of the factors fuelling the TB epidemic is the global rise of multidrug resistant TB (MDR-TB). The aim of this study was to determine the magnitude and factors associated with MDR-TB in the Tigray Region, Ethiopia., Method: This study employed a facility-based cross-sectional study design, which was conducted between July 2018 and August 2019. The inclusion criteria for the study participants were GeneXpert-positive who were not under treatment for TB, PTB patients' ≥15 years of age and who provided written informed consent. A total of 300 participants were enrolled in the study, with a structured questionnaire used to collect data on clinical, sociodemographic and behavioral factors. Sputum samples were collected and processed for acid-fast bacilli staining, culture and drug susceptibility testing. Drug susceptibility testing was performed using a line probe assay. Logistic regression was used to analyze associations between outcome and predictor variables., Results: The overall proportion of MDR-TB was 16.7% (11.6% and 32.7% for new and previously treated patients, respectively). Of the total MDR-TB isolates, 5.3% were pre-XDR-TB. The proportion of MDR-TB/HIV co-infection was 21.1%. A previous history of TB treatment AOR 3.75; 95% CI (0.7-2.24), cigarette smoking AOR 6.09; CI (1.65-2.50) and patients who had an intermittent fever (AOR = 2.54, 95% CI = 1.21-5.4) were strongly associated with MDR-TB development., Conclusions: The magnitude of MDR-TB observed among new and previously treated patients is very alarming, which calls for an urgent need for intervention. The high proportion of MDR-TB among newly diagnosed cases indicates ongoing transmission, which suggests the need for enhanced TB control program performance to interrupt transmission. The increased proportion of MDR-TB among previously treated cases indicates a need for better patient management to prevent the evolution of drug resistance. Assessing the TB control program performance gaps and an optimal implementation of the WHO recommended priority actions for the management of drug-resistant TB, is imperative to help reduce the current high MDR-TB burden in the study region., Competing Interests: The authors have declared that no competing interests exist

Rift valley fever virus (RVFV) is a causative agent of a viral zoonosis that constitutes a major clinical burden in wild and domestic ruminants. The virus causes major outbreaks in livestock (sheep, goats, cattle and camels) and can be transmitted to humans by contaminated animal products or via arthropod vectors. Human-to-human transmission has not been reported to date, but spill-over events from animals have led to outbreaks in humans in Africa and the Arabian Peninsula. Currently, there is no licensed human vaccine against RVFV and the virus is listed as a priority pathogen by the World Health Organisation (WHO) due to the high epidemic potential and the lack of effective countermeasures. Multiple large RVFV outbreaks have been reported since the virus was discovered. During the last two decades, over 4000 cases and ~1000 deaths have been reported. The lack of systematic surveillance to estimate the true burden and incidence of human RVF disease is a challenge for planning future vaccine efficacy evaluation. This creates a need for robust diagnostic methodologies that can be deployed in remote regions to aid case confirmation, assessment of seroprevalence as well as pathogen surveillance required for the different stages of vaccine evaluation. Here, we perform comprehensive landscaping of the available diagnostic solutions for detection of RVFV in humans. Based on the identified gaps in the currently available in-house and commercially available methods, we highlight the specific investment needs for diagnostics that are critical for accelerating the development of effective vaccines against RVFV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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

Background: Ethiopia is one of the countries with a high burden of tuberculosis (TB). Jimma Zone has the lowest TB case notification rate compared to the national and World Health Organization's (WHO) targets. The aim of the present study was to identify barriers, and explore the origin of these barriers in relation to TB case finding., Methods: A qualitative study was conducted by using different data collection methods and sources. Sixty in-depth interviews with TB treatment providers, program managers and TB patients were included. In addition, 42 governmental health facilities were observed for availability of resources. Data obtained from the in-depth interviews were transcribed, coded, categorized and thematized. Atlas.ti version 7.1 software was used for the data coding and categorizing., Results: Inadequate resources for TB case finding, such as a shortage of health-care providers, inadequate basic infrastructure, and inadequate diagnostic equipment and supplies, as well as limited access to TB diagnostic services such as an absence of nearby health facilities providing TB diagnostic services and health system delays in the diagnostic process, were identified as barriers for TB case finding. We identified the absence of trained laboratory professionals in 11, the absence of clean water supply in 13 and the electricity in seven health facilities. Furthermore, we found that difficult topography, the absence of proper roads, an inadequate collaboration with other sectors (such as education), a turnover of laboratory professionals, and a low community mobilization, as the origin of some of these barriers., Conclusion: Inadequate resources for TB case finding, and a limited access to diagnostic services, were major challenges affecting TB case finding. The optimal application of the directly observed treatment short course (Stop TB) strategy is crucial to increase the current low TB case notification rate. Practical strategies need to be designed to attract and retain health professionals in the health system., Competing Interests: There are no financial or non-financial competing interests among the authors. The authors have declared that no competing interests exist.

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.

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.

Background: Drug-resistant tuberculosis (DR-TB) remains a major health security threat worldwide. The effectiveness of implementation of DR-TB control strategies has been a subject of research and controversy. In resource-limited settings, using conventional medicine as the only framework to explain DR-TB gives a rather incomplete picture of the disease. This study intended to explore the perceptions and experiences of healthcare workers on the management and control of DR-TB in Addis Ababa, Ethiopia., Methods: The study employed a qualitative methodology with an inductive approach and a thematic analysis. It involved in-depth interviews with healthcare workers providing clinical services to DR-TB patients in 10 public healthcare facilities in Addis Ababa, Ethiopia., Results: A total of 18 healthcare workers participated until data saturation, which included 12 clinical nurses, four health officers and two medical laboratory technicians. The findings show that healthcare workers perceive DR-TB as a growing public health threat in Ethiopia, due to factors such as poverty, poor nutrition, crowded settings, healthcare worker and general public awareness of DR-TB, lack of good governance and culture., Conclusion: The perspectives drawn from the healthcare workers shed more light on the image of DR-TB in a developing country context. It has been shown that understanding DR-TB is not confined to what can be drawn from the sphere of biomedicine. There are also interconnected barriers, which predict a dystopia in the epidemiology of DR-TB. Bringing DR-TB under control requires taking a step back from an overwhelming focus on the biomedical facets of the disease, and employ critical thinking on the wider social and structural forces as equally important targets., Competing Interests: The authors have declared that no competing interests exist.

The molecular epidemiology of Mycobacterium tuberculosis (M. tuberculosis, Mtb) is poorly documented in Ethiopia. The data that exists has not yet been collected in an overview metadata form. Thus, this review summarizes available literature on the genomic diversity, geospatial distribution and transmission patterns of Mtb lineages (L) and sublineages in Ethiopia. Spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) based articles were identified from MEDLINE via PubMed and Scopus. The last date of article search was done on 12th February 2019. Articles were selected following the PRISMA flow diagram. The proportion of (sub)lineages was summarized at national level and further disaggregated by region. Clustering and recent transmission index (RTI) were determined using metan command and random effect meta-analysis model. The meta-analysis was computed using Stata 14 (Stata Corp. College Station, TX, USA). Among 4371 clinical isolates, 99.5% were Mtb and 0.5% were M. bovis. Proportionally, L4, L3, L1 and L7 made up 62.3%, 21.7%, 7.9% and 3.4% of the total isolates, respectively. Among sublineages, L4.2. ETH/SIT149, L4.10/SIT53, L3. ETH1/SIT25 and L4.6/SIT37 were the leading clustered isolates accounting for 14.4%, 9.7%, 7.2% and 5.5%, respectively. Based on MIRU-VNTR, the rate of clustering was 41% and the secondary case rate from a single source case was estimated at 29%. Clustering and recent transmission index was higher in eastern and southwestern Ethiopia compared with the northwestern part of the country. High level of genetic diversity with a high rate of clustering was noted which collectively mirrored the phenomena of micro-epidemics and super-spreading. The largest set of clustered strains deserves special attention and further characterization using whole genome sequencing (WGS) to better understand the evolution, genomic diversity and transmission dynamics of Mtb., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Preschool children in Addis Ababa, Ethiopia, are highly exposed to influenza viruses. Factors related to infections, nutrition, and environmental conditions that might explain the burden of influenza among these children were investigated. Ninety-five preschool children, 48 girls and 47 boys, were followed clinically for 12 months. Illness and immune responses to influenza; three other respiratory viruses; five airway pathogenic bacteria; and levels of vitamins D, A, and B12 were assessed. Most of the children had antibodies to numerous respiratory viral and bacterial agents at study start, and many were infected during follow-up. Twenty-five girls and 25 boys fell ill during the study, and were treated with one or more courses of systemic antimicrobials. Ninety percent of both girls and boys had 25-hydroxyvitamin D [25(OH)D] levels below the recommended levels. While there was no overall difference in the levels of vitamins D, A, and B12 between girls and boys, treated girls had significantly lower 25(OH)D levels than non-treated girls and treated boys. There was a considerable number of short for age children, but only the short treated girls had significantly lower 25(OH)D levels than the non-treated children. Preschool girls with low 25(OH)D levels were more vulnerable to pathogenic microbes than boys.

Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb). PTMs such as glycosylation play a significant role in Mtb adaptive processes. The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry. A total of 2944 glycosylation events were discovered in 1325 proteins. This data set represents the highest number of glycosylated proteins identified in Mtb to date. O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated. This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria. Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall. Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins. The differential glycosylation pattern may contribute to phenotypic variabilities across Mtb lineages. The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.

Lassa fever, caused by arenavirus Lassa virus (LASV), is an acute viral haemorrhagic disease that affects up to an estimated 300 000 individuals and causes up to 5000 deaths per year in West Africa. Currently available LASV diagnostic methods are difficult to operationalise in low-resource health centres and may be less sensitive to detecting all known or emerging LASV strains. To prioritise diagnostic development for LASV, we assessed the diagnostic applications for case detection, clinical management, surveillance, outbreak response, and therapeutic and vaccine development at various healthcare levels. Diagnostic development should prioritise point-of-care and near-patient diagnostics, especially those with the ability to detect all lineages of LASV, as they would allow for rapid detection in resource-limited health facilities closer to the patient., Competing Interests: Competing interests: None declared.

Background: Measuring the size of the infectious pool of tuberculosis (TB) is essential to understand the burden and monitor trends of TB control program performance. This study applied the concept of TB management time to estimate and compare the size of the TB infectious pool between 2009 and 2014 in West Gojjam Zone of Amhara Region, Ethiopia., Methods: New sputum smear-positive and smear-negative pulmonary TB (PTB) and retreatment cases who attended 30 randomly selected public health facilities in West Gojjam Zone from October 2013 to October 2014 were consecutively enrolled in the study. In order to determine the infectious period, the TB management time (number of days from the onset of cough until start of anti-TB treatment) was computed for each patient category. The number of undiagnosed TB cases was estimated and hence the TB management time for the undiagnosed category was calculated. The total size of the TB infectious pool during the study period for the study zone was estimated as the annual number of infectious person days., Results: New smear-positive and smear-negative PTB cases contributed 25,050 and 12,931 infectious person days per year to the TB infectious pool, respectively. The retreatment and presently undiagnosed cases contributed 8840 and 34,310 infectious person days per year, respectively. The total size of the TB infectious pool in West Gojjam Zone during the study period was estimated at 81,131 infectious person days per year or 3405 infectious person days per 100,000 population per year. Compared to a similar study done in 2009 in the study area, the current study showed reduction of the TB infectious pool by 244,279 infectious person days., Conclusions: TB management time is a simple and practical tool that may help to estimate and compare the changes in the size of the TB infectious pool at local level. It may also be used as an indicator to monitor the changes in TB control program performance.

Background: Trachoma is chronic kerato conjunctivitis, which is caused by repeated infection with Chlamydia trachomatis bacterium. It is hyper endemic in many rural areas of Ethiopia. The objective of this study was to measure the effect of water, sanitation and hygiene interventions on active trachoma in selected woredas of North and South Wollo zones of Amhara Region, Ethiopia., Methodology: A community based quasi-experimental study was conducted from October 2014 to December 2015 among children aged 1-8 years at baseline and among one year older same children after intervention. A four-stage random cluster-sampling technique was employed to select study participants. From each selected household, one child was clinically assessed for active trachoma. Structured questionnaire was used to collect socio demographic and behavioral data. MacNemar test was applied to compare the prevalence of active trachoma between baseline and after the intervention period at both intervention and non-intervention study areas., Results: The prevalence of active trachoma was reduced from baseline prevalence of 26% to 18% after one-year intervention period in the intervention woredas (P≤0.001). MacNemar test result showed significant reduction of active trachoma prevalence after the intervention period in the intervention woredas compared to the non-intervention woredas (P≤0.001). Water, sanitation and hygiene related activities were significantly improved after the intervention period in the intervention woredas (P<0.05)., Conclusions: There was a significant reduction of active trachoma prevalence between the baseline and after the intervention period in the intervention woredas, but not in the non-intervention ones. Improved water, sanitation and hygiene interventions contributed to the reduction of active trachoma. However, the magnitude of active trachoma prevalence observed after the intervention is still very high in the studied areas of North and South Wollo Zones communities. To achieve the global trachoma elimination target by the year 2020 as set by the WHO, continued WaSH interventions and periodic monitoring, evaluation and reporting of the impact of WaSH on active trachoma is warranted.

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 N ε - 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 N ε -acetylation sites, derived from 953 unique proteins. Mtb O-acetylation was thereby significantly more abundant than N ε -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.

Background: Trachoma is a disease of the eye, caused by the bacteria Chlamydia trachomatis, which can lead to blindness if left untreated. Ethiopia is one of the most trachoma-affected countries in the world. The objective of this study was to determine the prevalence of and associated risk factors for active trachoma among children in selected woredas of North and South Wollo Zones in Amhara Region, Ethiopia., Methods: This study was a community-based, cross-sectional study, which was conducted from October to December 2014 among children aged 1-8. A four-stage random cluster sampling technique was employed to select the study areas and participants. From each selected household, one child was clinically assessed for active trachoma. A structured questionnaire was used to collect sociodemographic, behavioral, and clinical data. Multivariate logistic regression analysis was used to analyze the association between predictor variables and active trachoma., Results: The overall prevalence of active trachoma among 1358 children was found to be 21.6% (95% CI: 19.4-23.8%). When analyzed by the presence or absence of individual WHO simplified system signs of active trachoma, trachomatous inflammation-follicular cases constituted18% (95% CI: 15.9-20.2%), while 4.7% (95% CI: 3.6-5.8%) were trachomatous inflammation-intense cases. Ocular discharge (aOR = 5.2; 95% CI: 3.3-8.2), nasal discharge (aOR = 1.8; 95% CI: 1.2-2.7), time taken to fetch water (aOR = 0.02; 95% CI: 0.01-0.05), frequency of hand and face washing (aOR = 4.4; 95% CI: 1.1-17.8), and access to a latrine (aOR = 0.006; 95% CI: 0.001-0.030) were found to be independently associated with the presence of active trachoma., Conclusions: There is a high burden of active trachoma among children in the study areas. Lack of personal hygiene and limited access to a safe water supply and latrines were associated with increased prevalence of active trachoma. In order to reduce the burden of active trachoma, facial cleanliness and environmental improvement components of the SAFE strategy should be upgraded in the study areas.

In order to decipher the nature of the slowly growing Mycobacterium tuberculosis (M .tuberculosis) lineage 7, the differentially abundant proteins in strains of M. tuberculosis lineage 7 and lineage 4 were defined. Comparative proteomic analysis by mass spectrometry was employed to identify, quantitate and compare the protein profiles of strains from the two M. tuberculosis lineages. Label-free peptide quantification of whole cells from M. tuberculosis lineage 7 and 4 yielded the identification of 2825 and 2541 proteins, respectively. A combined total of 2867 protein groups covering 71% of the predicted M. tuberculosis proteome were identified. The abundance of 125 proteins in M. tuberculosis lineage 7 and 4 strains was significantly altered. Notably, the analysis showed that a number of M. tuberculosis proteins involved in growth and virulence were less abundant in lineage 7 strains compared to lineage 4. Five ABC transporter proteins, three phosphate binding proteins essential for inorganic phosphate uptake, and six components of the type 7 secretion system ESX-3 involved in iron acquisition were less abundant in M. tuberculosis lineage 7. This proteogenomic analysis provided an insight into the lineage 7-specific protein profile which may provide clues to understanding the differential properties of lineage 7 strains in terms of slow growth, survival fitness, and pathogenesis.

Introduction: The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a major global public health concern. There is mounting evidence from different countries on the burden of TB and DM comorbidity. The objective of this systematic review was to summarize the existing evidence on prevalence and associated/risk factors of TBDM comorbidity at global and regional levels., Methods: Ovid Medline, Embase, Global health, Cochrane library, Web of science and Scopus Elsevier databases were searched to identify eligible articles for the systematic review. Data were extracted using standardized excel form and pilot tested. Median with interquartile range (IQR) was used to estimate prevalence of TBDM comorbidity. Associated/risk factors that were identified from individual studies were thematically analyzed and described., Results: The prevalence of DM among TB patients ranged from 1.9% to 45%. The overall median global prevalence was 16% (IQR 9.0%-25.3%) Similarly, the prevalence of TB among DM patients ranged from 0.38% to 14% and the overall median global prevalence was 4.1% (IQR 1.8%-6.2%). The highest prevalence of DM among TB patients is observed in the studied countries of Asia, North America and Oceania. On the contrary, the prevalence of TB among DM patients is low globally, but relatively higher in the studied countries of Asia and the African continents. Sex, older age, urban residence, tobacco smoking, sedentary lifestyle, poor glycemic control, having family history of DM and TB illness were among the variables identified as associated/risk factors for TBDM comorbidity., Conclusion: This systematic review revealed that there is a high burden of DM among TB patients at global level. On the contrary, the global prevalence of TB among DM patients is low. Assessing the magnitude and risk/associated factors of TBDM comorbidity at country/local level is crucial before making decisions to undertake TBDM integrated services.

Background: Influenza in children who reside in tropical and subtropical regions has until recently been regarded as insignificant. However, new evidence suggests that it significantly impacts hospitalization and promotes secondary bacterial coinfections. Ethiopia is situated in a subtropical area where influenza viruses are likely to circulate year round., Methods: Clinical data were recorded in a cohort of 103 healthy preschool children recruited in Addis Ababa, Ethiopia. Humoral and cellular immune responses to influenza virus were determined by hemagglutination inhibition (HI) and interferon-γ enzyme-linked immunospot assays., Results: Ninety-six percent of the children (2-5 years old) had pre-existing HI antibody responses to 1 or more of the circulating influenza A subtypes, H1N1 (51%), H3N2 (86%), or influenza B (51%) strains. At the age of 4, all children had been infected with at least 1 strain, and 75% had been infected with 2-4 different viral strains. CD4 + and CD8 + T-cell responses against conserved viral antigens increased with repeated exposures, indicating boosting of cross-reactive cellular immunity. Malnutrition did not seem to affect these immune responses to influenza., Conclusions: Influenza is highly prevalent among children in this area of Ethiopia. Due to the risk of secondary bacterial pneumonia, increased influenza awareness might benefit child health., (© The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.

Background: delay in diagnosis and treatment of tuberculosis (TB) may worsen the disease, increase mortality and enhance transmission in the community. This study aimed at assessing the association between total delay and unfavorable treatment outcome among newly diagnosed pulmonary TB (PTB) patients., Methods: A prospective cohort study was conducted in West Gojjam Zone, Amhara Region of Ethiopia from October 2013 to May 2015. Newly diagnosed PTB patients who were ≥15 years of age were consecutively enrolled in the study from 30 randomly selected public health facilities. Total delay (the time period from onset of TB symptoms to first start of anti-TB treatment) was measured. Median total delay was calculated. Mixed effect logistics regression was used to analyze factors associated with unfavorable treatment outcome., Results: Seven hundred six patients were enrolled in the study. The median total delay was 60 days. Patients with total delay of > 60 days were more likely to have unfavorable TB treatment outcome than patients with total delay of ≤ 60 days (adjusted odds ratio [AOR], 2.33; 95% confidence interval [CI], 1.04-5.26). Human immunodeficiency virus (HIV) positive TB patients were 8.46 times more likely to experience unfavorable treatment outcome than HIV negative TB patients (AOR, 8.46; 95% CI, 3.14-22.79)., Conclusions: Long total delay and TB/HIV coinfection were associated with unfavorable treatment outcome. Targeted interventions that can reduce delay in diagnosis and treatment of TB, and early comprehensive management of TB/HIV coinfection are needed to reduce increased risk of unfavorable treatment outcome.

Background: A deeply rooted phylogenetic lineage of Mycobacterium tuberculosis (M. tuberculosis) termed lineage 7 was discovered in Ethiopia. Whole genome sequencing of 30 lineage 7 strains from patients in Ethiopia was performed. Intra-lineage genome variation was defined and unique characteristics identified with a focus on genes involved in DNA repair, recombination and replication (3R genes)., Results: More than 800 mutations specific to M. tuberculosis lineage 7 strains were identified. The proportion of non-synonymous single nucleotide polymorphisms (nsSNPs) in 3R genes was higher after the recent expansion of M. tuberculosis lineage 7 strain started. The proportion of nsSNPs in genes involved in inorganic ion transport and metabolism was significantly higher before the expansion began. A total of 22346 bp deletions were observed. Lineage 7 strains also exhibited a high number of mutations in genes involved in carbohydrate transport and metabolism, transcription, energy production and conversion., Conclusions: We have identified unique genomic signatures of the lineage 7 strains. The high frequency of nsSNP in 3R genes after the phylogenetic expansion may have contributed to recent variability and adaptation. The abundance of mutations in genes involved in inorganic ion transport and metabolism before the expansion period may indicate an adaptive response of lineage 7 strains to enable survival, potentially under environmental stress exposure. As lineage 7 strains originally were phylogenetically deeply rooted, this may indicate fundamental adaptive genomic pathways affecting the fitness of M. tuberculosis as a species.

Lineage 7 of the Mycobacterium tuberculosis complex has recently been identified among strains originating from Ethiopia. Using different DNA typing techniques, this study provides additional information on the genetic heterogeneity of five lineage 7 strains collected in the Amhara Region of Ethiopia. It also confirms the phylogenetic positioning of these strains between the ancient lineage 1 and TbD1-deleted, modern lineages 2, 3 and 4 of Mycobacterium tuberculosis . Four newly identified large sequence polymorphisms characteristic of the Amhara Region lineage 7 strains are described. While lineage 7 strains have been previously identified in the Woldiya area, we show that lineage 7 strains circulate in other parts of the Amhara Region and also among foreign-born individuals from Eritrea and Somalia in The Netherlands. For ease of documenting future identification of these strains in other geographical locations and recognizing the place of origin, we propose to assign lineage 7 strains the lineage name ' Aethiops vetus ' .

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.

Background: There is growing evidence suggesting that diabetes mellitus (DM) affects disease presentation and treatment outcome in tuberculosis (TB) patients. This study aimed at investigating the role of DM on clinical presentations and treatment outcomes among newly diagnosed TB patients., Methods: A prospective cohort study was conducted in South-Eastern Amhara Region, Ethiopia from September 2013 till March 2015. Study subjects were consecutively recruited from 44 randomly selected health facilities in the study area. Participants were categorized into two patient groups, namely, patients with TB and DM (TBDM) and TB patients without DM (TBNDM). Findings on clinical presentations and treatment outcomes were compared between the two patient groups. Cox proportional hazard regression analysis was applied to identify factors associated with death., Results: Out of 1314 TB patients enrolled in the study, 109 (8.3 %) had coexisting DM. TBDM comorbidity [adjusted hazard ratio (AHR) 3.96; 95 % confidence interval (C.I.) (1.76-8.89)], and TB coinfection with human immunodeficiency virus (HIV) [AHR 2.59; 95 % C.I. (1.21-5.59)] were associated with increased death. TBDM and TBNDM patients did not show significant difference in clinical symptoms at baseline and during anti-TB treatment period. However, at the 2(nd) month of treatment, TBDM patients were more symptomatic compared to patients in the TBNDM group., Conclusions: The study showed that DM is associated with increased death during TB treatment. DM has no association with clinical presentation of TB except at the end of the intensive phase treatment. Routine screening of TB patients for DM is recommended for early diagnosis and treatment of patients with TBDM comorbidity.

Background: The association between diabetes mellitus (DM) and tuberculosis (TB) is re-emerging worldwide. Recently, the prevalence of DM is increasing in resource poor countries where TB is of high burden. The objective of the current study was to determine the prevalence and analyze associated factors of TB and DM comorbidity in South-Eastern Amhara Region, Ethiopia., Methods: This was a facility based cross-sectional study. All newly diagnosed TB patients attending selected health facilities in the study area were consecutively screened for DM. DM was diagnosed based on the World Health Organization diagnostic criteria. A pre-tested semi-structured questionnaire was used to collect socio-demographic, lifestyles and clinical data. Logistic regression analysis was performed to identify factors associated with TB and DM comorbidity., Result: Among a total of 1314 patients who participated in the study, the prevalence of DM was estimated at 109 (8.3%). Being female [odds ratio (OR) 1.70; 95% confidence interval (CI) (1.10-2.62)], patients age [41-64 years (OR 3.35; 95% CI (2.01-5.57), 65-89 years (OR 3.18; 95% CI (1.52-6.64)], being a pulmonary TB case [(OR 1.69; 95% CI 1.09-2.63)] and having a family history of DM [(OR 4.54; 95% CI (2.36-8.73)] were associated factors identified with TB and DM comorbidity., Conclusion: The prevalence of DM among TB patients in South-Eastern Amahra Region is high. Routine screening of TB patients for DM is recommended in the study area.

Background. Weak health systems pose many barriers to effective tuberculosis (TB) control. This study aimed at exploring health worker's and TB control program coordinator's perspectives on health systems challenges facing TB control in West Gojjam Zone, Amhara Region, Ethiopia. Methods. This was a qualitative descriptive study. Eight in-depth interviews with TB control program coordinators and two focus group discussions among 16 health workers were conducted. Purposive sampling was used to recruit study participants. Thematic analysis was used to identify and analyse main themes. Results. We found that intermittent interruptions of laboratory reagents and anti-TB drugs supplies, absence of trained and motivated health workers, poor TB data documentation, lack of adherence to TB treatment guideline, and lack of access to TB diagnostic tools at peripheral health institutions were challenges facing the TB control program performance in the study zone. Conclusions. Ensuring uninterrupted supply of anti-TB drugs and laboratory reagents to all health institutions is essential. Continuous refresher training of health workers on standard TB care and data handling and developing and implementing a sound retention strategy to attract and motivate health professionals to work in rural areas are necessary interventions to improve the TB control program performance in the study zone.

Recent genotyping studies of Mycobacterium tuberculosis in Ethiopia have reported the identification of a new phylogenetically distinct M. tuberculosis lineage, lineage 7. We therefore investigated the genetic diversity and association of specific M. tuberculosis lineages with sociodemographic and clinical parameters among pulmonary TB patients in the Amhara Region, Ethiopia. DNA was isolated from M. tuberculosis-positive sputum specimens (n=240) and analyzed by PCR and 24-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) analysis and spoligotyping. Bioinformatic analysis assigned the M. tuberculosis genotypes to global lineages, and associations between patient characteristics and genotype were evaluated using logistic regression analysis. The study revealed a high diversity of modern and premodern M. tuberculosis lineages, among which approximately 25% were not previously reported. Among the M. tuberculosis strains (n=138) assigned to seven subgroups, the largest cluster belonged to the lineage Central Asian (CAS) (n=60; 26.0%), the second largest to lineage 7 (n=36; 15.6%), and the third largest to the lineage Haarlem (n=35; 15.2%). Four sublineages were new in the MIRU-VNTRplus database, designated NW-ETH3, NW-ETH1, NW-ETH2, and NW-ETH4, which included 24 (10.4%), 18 (7.8%), 8 (3.5%), and 5 (2.2%) isolates, respectively. Notably, patient delay in seeking treatment was significantly longer among patients infected with lineage 7 strains (Mann-Whitney test, P<0.008) than in patients infected with CAS strains (adjusted odds ratio [AOR], 4.7; 95% confidence interval [CI], 1.6 to 13.5). Lineage 7 strains also grew more slowly than other M. tuberculosis strains. Cases of Haarlem (OR, 2.8; 95% CI, 1.2 to 6.6) and NW-ETH3 (OR, 2.8; 95% CI, 1.0 to 7.3) infection appeared in defined clusters. Intensified active case finding and contact tracing activities in the study region are needed to expedite diagnosis and treatment of TB., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objective: To demonstrate the application of TB management time as an alternative parameter to estimate the size of the tuberculosis infectious pool in West Gojjam Zone of Amhara Region, Ethiopia., Methods: In this study, we used the TB management time, i.e. the number of days from start of cough until start of treatment, to determine the infectious period. Patients with sputum smear-positive and smear-negative pulmonary TB, retreatment and an estimated number of undetected cases were included. The infectious pool was then estimated as the annual number of infectious person days in a defined population., Results: The TB management time of presently undiagnosed TB cases and sputum smear-positive patients contributed significantly to the infectious pool with 151,840 and 128,750 infectious person days per year, respectively. The total infectious pool including sputum smear-negative TB cases and retreatment patients in the study area was estimated at 325,410 person days or 15,447 person days per 100,000 population during the study year., Conclusion: Recording TB management time may be used to estimate the infectious pool of TB and to monitor programme performance in the community., (© 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: Early detection and treatment of TB is essential for the success of TB control program performance. The aim of this study was to determine the length and analyze predictors of patients', health systems' and total delays among patients attending a referral hospital in Bahir Dar, Ethiopia., Methods: A cross-sectional study was conducted among newly diagnosed TB cases ≥ 15 years of age. Delay was analyzed at three levels: the periods between 1) onset of TB symptoms and first visit to medical provider, i.e. patients' delay, 2) the first visit to a medical provider and the initiation of treatment i.e. health systems' delay and 3) onset of TB symptoms and initiation of treatment i.e. total delay. Uni- and multi-variate logistic regression analyses were performed to investigate predictors of patients', health systems' and total delays., Results: The median time of patients' delay was 21 days [(interquartile range (IQR) (7 days, 60 days)]. The median health systems' delay was 27 days (IQR 8 days, 60 days) and the median total delay was 60 days (IQR 30 days, 121 days). Patients residing in rural areas had a three-fold increase in patients' delay compared to those from urban areas [Adjusted Odds Ratio (AOR) 3.4; 95% (CI 1.3, 8.9)]. Extra-pulmonary TB (EPTB) cases were more likely to experience delay in seeking treatment compared to pulmonary (PTB) cases [(AOR 2.6; 95% (CI 1.3, 5.4)]. Study subjects who first visited health centres [(AOR) 5.1; 95% (CI 2.1, 12.5)], private facilities [(AOR) 3.5; 95% (CI 1.3, 9.7] and health posts [(AOR) 109; 95% (CI 12, 958], were more likely to experience an increase in health systems' delay compared to those who visited hospitals., Conclusions: The majority of TB patients reported to medical providers within an acceptable time after the onset of symptoms. Rural residence was associated with patients' and total delays. Providing the population with information about TB symptoms and the importance of early health seeking may be an efficient way to decrease TB transmission, morbidity and mortality. Establishing efficient TB diagnostic and treatment facilities at the periphery level is imperative to reduce diagnostic delay and expedite TB treatment.

The aim of this study was to characterize Mycobacterium tuberculosis isolates circulating in the Amhara Region of Ethiopia. Sputum samples were collected from new pulmonary tuberculosis (TB) patients in the Region. Genotyping of mycobacterial DNA was performed by spoligotyping and isolates were assigned to families using the SpolDB4 and the model-based program 'Spotclust'. A high level of diversity was found among the 237 isolates. Sixty-five different spoligopatterns were obtained. The T (30.8%), Central Asian (CAS; 21.1%) and U (17.7%) families were the predominant isolates comprising 69.6% of the total strains. Eighty-five per cent of the U lineage belonged to Spoligo-International-Type (SIT) 910 and SIT 1729. Only a few of these strains are included in SpolDB4 to date. Of the total strains, 41 (17.3%) were unique and have not been described in SpolDB4 to date. This study indicated that the TB epidemic in Amhara Region, Ethiopia, is characterized by the circulation of numerous M. tuberculosis strain families. The high proportion of SIT 910 and SIT 1729 strains may indicate an increase in the importance of these lineages in the transmission of TB in the study region., (© 2013 APMIS. Published by John Wiley & Sons Ltd.)