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1.
BMC Infect Dis ; 24(1): 499, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760665

ABSTRACT

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.


Subject(s)
Antitubercular Agents , COVID-19 , HIV Infections , Tuberculosis , Humans , Retrospective Studies , Ethiopia/epidemiology , Adult , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/complications , Female , Male , Tuberculosis/prevention & control , Tuberculosis/epidemiology , Tuberculosis/drug therapy , Middle Aged , COVID-19/prevention & control , COVID-19/epidemiology , Antitubercular Agents/therapeutic use , Antitubercular Agents/administration & dosage , Young Adult , Adolescent , Isoniazid/therapeutic use , Isoniazid/administration & dosage , SARS-CoV-2 , Mass Screening/statistics & numerical data
2.
BMJ Glob Health ; 9(4)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688565

ABSTRACT

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.


Subject(s)
Diagnostic Tests, Routine , Disease Outbreaks , Humans , Disease Outbreaks/prevention & control , COVID-19/prevention & control , COVID-19/diagnosis , Pandemics/prevention & control , Global Health , Rapid Diagnostic Tests
3.
NPJ Vaccines ; 8(1): 95, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37391580

ABSTRACT

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.

4.
PLoS One ; 18(2): e0281546, 2023.
Article in English | MEDLINE | ID: mdl-36757943

ABSTRACT

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.


Subject(s)
Tuberculosis, Pulmonary , Tuberculosis , Male , Humans , Female , Tuberculosis, Pulmonary/diagnosis , Ethiopia/epidemiology , Cross-Sectional Studies , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/drug therapy , Surveys and Questionnaires , Delayed Diagnosis
5.
Reprod Health ; 19(1): 42, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35164776

ABSTRACT

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.


Subject(s)
COVID-19 , Child Health Services , Maternal Health Services , Child , Child Health , Communicable Disease Control , Cross-Sectional Studies , Ethiopia/epidemiology , Female , Humans , Pandemics , Pregnancy , SARS-CoV-2
6.
ACS Omega ; 7(4): 3470-3482, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35128256

ABSTRACT

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.

7.
Front Microbiol ; 12: 743198, 2021.
Article in English | MEDLINE | ID: mdl-34938276

ABSTRACT

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.

9.
Lipids Health Dis ; 20(1): 129, 2021 Oct 03.
Article in English | MEDLINE | ID: mdl-34602073

ABSTRACT

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.


Subject(s)
Lipid Droplets , Mycobacterium tuberculosis/metabolism , Transcriptome , Tuberculosis/metabolism , Host-Pathogen Interactions , Humans , Macrophages , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/physiology , Sputum/microbiology , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis/transmission
10.
Int J Public Health ; 66: 633917, 2021.
Article in English | MEDLINE | ID: mdl-34434083

ABSTRACT

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.


Subject(s)
Health Personnel , Tuberculosis, Multidrug-Resistant , Ethiopia/epidemiology , Female , Health Facilities , Health Personnel/psychology , Health Personnel/statistics & numerical data , Health Resources/supply & distribution , Health Workforce , Humans , Male , Qualitative Research , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/therapy
11.
BMJ Open ; 11(7): e048369, 2021 07 21.
Article in English | MEDLINE | ID: mdl-34290068

ABSTRACT

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.


Subject(s)
Pharmaceutical Preparations , Tuberculosis , Adolescent , Antitubercular Agents/therapeutic use , Directly Observed Therapy , Ethiopia/epidemiology , Humans , Prospective Studies , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis/epidemiology
12.
Clin Trials ; 18(3): 286-294, 2021 06.
Article in English | MEDLINE | ID: mdl-33653146

ABSTRACT

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.


Subject(s)
Clinical Trials as Topic , Communicable Diseases, Emerging , Epidemics , Vaccines , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Epidemics/prevention & control , Humans , Research Design , Time
13.
PLoS One ; 16(1): e0245378, 2021.
Article in English | MEDLINE | ID: mdl-33449953

ABSTRACT

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.


Subject(s)
Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Ethiopia/epidemiology , Female , Health Facilities , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Rural Population , Spatio-Temporal Analysis , Young Adult
14.
J Glob Antimicrob Resist ; 24: 6-13, 2021 03.
Article in English | MEDLINE | ID: mdl-33279682

ABSTRACT

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.


Subject(s)
Drug Resistance, Bacterial/genetics , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Antitubercular Agents/pharmacology , Cross-Sectional Studies , Ethiopia/epidemiology , Humans , Microbial Sensitivity Tests , Mutation , Mycobacterium tuberculosis/genetics , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/microbiology
15.
Front Microbiol ; 11: 550760, 2020.
Article in English | MEDLINE | ID: mdl-33072011

ABSTRACT

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.

16.
PLoS One ; 15(8): e0236362, 2020.
Article in English | MEDLINE | ID: mdl-32797053

ABSTRACT

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.


Subject(s)
HIV Infections/drug therapy , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antitubercular Agents/therapeutic use , Cross-Sectional Studies , Ethiopia/epidemiology , Female , HIV Infections/epidemiology , HIV Infections/microbiology , HIV Infections/pathology , Humans , Isoniazid/therapeutic use , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/pathogenicity , Rifampin/therapeutic use , Risk Factors , Sputum/drug effects , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/pathology , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathology , Young Adult
17.
Am J Trop Med Hyg ; 103(4): 1455-1465, 2020 10.
Article in English | MEDLINE | ID: mdl-32748766

ABSTRACT

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.


Subject(s)
Patient Acceptance of Health Care/statistics & numerical data , Surveys and Questionnaires , Tuberculosis/diagnosis , Adult , Ethiopia/epidemiology , Female , Focus Groups , Health Facilities , Health Personnel , Health Services , Humans , Male , Rural Population
18.
Res Rep Trop Med ; 11: 3-16, 2020.
Article in English | MEDLINE | ID: mdl-32099509

ABSTRACT

BACKGROUND: 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.

19.
PLoS One ; 15(1): e0226307, 2020.
Article in English | MEDLINE | ID: mdl-31895932

ABSTRACT

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.


Subject(s)
Health Facilities/supply & distribution , Health Personnel/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Health Services/supply & distribution , Patient Acceptance of Health Care , Tuberculosis/diagnosis , Adult , Ethiopia/epidemiology , Female , Humans , Male , Mycobacterium tuberculosis/physiology , Qualitative Research , Tuberculosis/epidemiology , Tuberculosis/microbiology , Young Adult
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