SARS-CoV-2 co-detection with influenza and human respiratory syncytial virus in Ethiopia: Findings from the severe acute respiratory illness (SARI) and influenza-like illness (ILI) sentinel surveillance, January 01, 2021, to June 30, 2022.

SARS-CoV-2 co-infection with the influenza virus or human respiratory syncytial virus (RSV) may complicate its progress and clinical outcomes. However, data on the co-detection of SARS-CoV-2 with other respiratory viruses are limited in Ethiopia and other parts of Africa to inform evidence-based response and decision-making. We analyzed 4,989 patients' data captured from the national severe acute respiratory illness (SARI) and influenza-like illness (ILI) sentinel surveillance sites over 18 months period from January 01, 2021, to June 30, 2022. Laboratory specimens were collected from the patients and tested for viral respiratory pathogens by real-time, reverse transcription polymerase chain reaction (RT-PCR) at the national influenza center. The median age of the patients was 14 years (IQR: 1-35 years), with a slight preponderance of them being at the age of 15 to less than 50 years. SARS-CoV-2 was detected among 459 (9.2%, 95% CI: 8.4-10.0) patients, and 64 (1.3%, 95% CI: 1.0-1.6) of SARS-CoV-2 were co-detected either with Influenza virus (54.7%) or RSV (32.8%) and 12.5% were detected with both of the viruses. A substantial proportion (54.7%) of SARS-CoV-2 co-detection with other respiratory viruses was identified among patients in the age group from 15 to less than 50 years. The multivariable analysis found that the odds of SARS-CoV-2 co-detection was higher among individuals with the age category of 20 to 39 years as compared to those less than 20 years old (AOR: 1.98, 95%CI:1.15-3.42) while the odds of SARS-CoV-2 co-detection was lower among cases from other regions of the country as compared to those from Addis Ababa (AOR:0.16 95%CI:0.07-0.34). Although the SARS-CoV-2 co-detection with other respiratory viral pathogens was minimal, the findings of this study underscore that it is critical to continuously monitor the co-infections to reduce transmission and improve patient outcomes, particularly among the youth and patients with ILI.

The burden of severe asthma in sub-Saharan Africa: Findings from the African Severe Asthma Project.

Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.

Genotype characterization of Epstein-Barr virus among adults living with human immunodeficiency virus in Ethiopia.

Background: Epstein-Barr virus (EBV) is a human lymphotropic herpesvirus with a causative agent in cancer. There are two genotypes of EBV (EBV genotype 1 and EBV genotype 2) that have been shown to infect humans. This study aimed to characterize the EBV genotype among people with human immunodeficiency virus (PWH) and HIV-negative individuals in Ethiopia. Methods: DNA was extracted from peripheral blood mononuclear cells (PBMCs). Conventional polymerase chain reaction (cPCR) targeting EBNA3C genes was performed for genotyping. A quantitative real-time PCR (q-PCR) assay for EBV DNA (EBNA1 ORF) detection and viral load quantification was performed. Statistical significance was determined at a value of p < 0.05. Result: In this study, 155 EBV-seropositive individuals were enrolled, including 128 PWH and 27 HIV-negative individuals. Among PWH, EBV genotype 1 was the most prevalent (105/128, 82.0%) genotype, followed by EBV genotype 2 (17/128, 13.3%), and mixed infection (6/128, 4.7%). In PWH, the median log10 of EBV viral load was 4.23 copies/ml [interquartile range (IQR): 3.76-4.46], whereas it was 3.84 copies/ml (IQR: 3.74-4.02) in the HIV-negative group. The EBV viral load in PWH was significantly higher than that in HIV-negative individuals (value of p = 0.004). In PWH, the median log10 of EBV viral load was 4.25 copies/ml (IQR: 3.83-4.47) in EBV genotype 1 and higher than EBV genotype 2 and mixed infection (p = 0.032). Conclusion: In Ethiopia, EBV genotype 1 was found to be the most predominant genotype, followed by EBV genotype 2. Understanding the genotype characterization of EBV in PWH is essential for developing new and innovative strategies for preventing and treating EBV-related complications in this population.

The Burden of Epstein-Barr Virus (EBV) and Its Determinants among Adult HIV-Positive Individuals in Ethiopia.

Epstein-Barr virus (EBV) is a well-known risk factor for the development of nasopharyngeal carcinoma, Hodgkin's lymphoma (HL), and Non-Hodgkin's lymphoma (NHL). People with HIV infection (PWH) are at increased risk for EBV-associated malignancies such as HL and NHL. Nevertheless, there are limited data on the burden of EBV among this population group in Ethiopia. Hence, this study aimed to determine the burden of EBV infection among adult HIV-positive individuals in Ethiopia and assess the determinants of EBV DNA positivity. We conducted a cross-sectional study at the Tikur Anbessa Specialised Hospital from March 2020 to March 2021. Two hundred and sixty individuals were enrolled in this study, including 179 HIV-positive and 81 HIV-negative individuals. A structured questionnaire was used to capture demographic and individual attributes. In addition, the clinical data of patients were also retrieved from clinical records. EBV viral capsid antigen (VCA) IgG antibody was measured by multiplex flow immunoassay, and EBV DNA levels were tested by quantitative real-time polymerase chain reaction (q-PCR) assays targeting the EBNA-1 open reading frame (ORF). Descriptive statistics were conducted to assess each study variable. A multivariable logistic regression model was applied to evaluate the determinants of EBV infection. Statistical significance was determined at a p-value < 0.05. Two hundred and fifty-three (97.7%) study participants were seropositive for the EBV VCA IgG antibody. Disaggregated by HIV status, 99.4% of HIV-positive and 93.8% of HIV-negative participants were EBV seropositive. In this study, 49.7% of HIV-positive and 24.7% of HIV-negative individuals were EBV DNA positive. PWH had a higher risk of EBV DNA positivity at 3.05 times (AOR: 3.05, 95% CI: 1.40-6.67). Moreover, among PWH, those with an HIV viral load greater than 1000 RNA copies/mL (AOR = 5.81, 95% CI = 1.40, 24.13) had a higher likelihood of EBV DNA positivity. The prevalence of EBV among PWH was significantly higher than among HIV-negative individuals. Higher HIV viral loads in PWH were associated with an increased risk of EBV DNA positivity. Since the increases in the viral load of EBV DNA among PWH could be related to the risk of developing EBV-associated cancers, it is necessary for more research on the role of EBV in EBV-associated cancer in this population group to be carried out.

Attitudes of Older Adult Patients and Caregivers Towards Deprescribing of Medications in Ethiopia.

Background: Deprescribing is essential for reducing inappropriate medication use and polypharmacy. For a holistic approach, it is essential to know how older adult patients and their caregivers perceive deprescribing. Objective: To assess the attitude of older adult patients and caregivers towards deprescribing medication at Ambo University Referral Hospital. Methodology: Institutional-based cross-sectional study was conducted using the revised Patients' Attitude Towards Deprescribing tool (rPATD). The data was analyzed using the SPSS-25 software. Backward linear regression and logistic regression were used to measure association between outcome and determinant variables. The two-sided P-value ≤0.05 with 95% confidence interval was utilized for reporting significant factors. Results: One hundred fifty-six (81.3%) of the respondents (ie, 85.0% of older adult and 77.2% of caregivers) agreed to stop one or more of their regular medications if the physician said it was possible despite 98 (51.0%) of them (ie, 49.0% of older adult and 53.3% of caregivers) being satisfied with their/their care recipient's medications. On the overall aggregate mean score, the respondents had a neutral position (2.6-3.59) regarding the burden and concerns of stopping medications whereas the majority of them disagree (1.0-2.59) with the inappropriateness of the medication they were taking and agreed (3.6-5.0) with the need for their involvement in treatment decision making. Concerns about stopping medicine scores (AOR = 0.440, 95% CI = 0.262-0.741, P = 0.035) and perceived levels of medication inappropriateness (AOR = 0.653, 95% CI = 0.456-0.936, P = 0.020) was significantly associated with the willingness to discontinue and overall satisfaction with their medicine regimen respectively. Conclusion: The majority of older adult patients and caregivers would like to deprescribe if the physicians recommended it. The perceived concerns of stopping and inappropriateness of the medicines were associated with the willingness to deprescribe and overall satisfaction with their medicine respectively. Healthcare providers should prompt the deprescribing process with older adult patients and caregivers by addressing their concerns about stopping medications.

Prevalence and Load of the Campylobacter Genus in Infants and Associated Household Contacts in Rural Eastern Ethiopia: a Longitudinal Study from the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) Project.

In our previous cross-sectional study, multiple species of Campylobacter were detected (88%) in stool samples from children (12 to 14 months of age) in rural eastern Ethiopia. This study assessed the temporal fecal carriage of Campylobacter in infants and identified putative reservoirs associated with these infections in infants from the same region. The prevalence and load of Campylobacter were determined using genus-specific real-time PCR. Stool samples from 106 infants (n = 1,073) were collected monthly from birth until 376 days of age (DOA). Human stool samples (mothers and siblings), livestock feces (cattle, chickens, goats, and sheep), and environmental samples (soil and drinking water) from the 106 households were collected twice per household (n = 1,644). Campylobacter was most prevalent in livestock feces (goats, 99%; sheep, 98%; cattle, 99%; chickens, 93%), followed by human stool samples (siblings, 91%; mothers, 83%; infants, 64%) and environmental samples (soil, 58%; drinking water, 43%). The prevalence of Campylobacter in infant stool samples significantly increased with age, from 30% at 27 DOA to 89% at 360 DOA (1% increase/day in the odds of being colonized) (P < 0.001). The Campylobacter load increased linearly (P < 0.001) with age from 2.95 logs at 25 DOA to 4.13 logs at 360 DOA. Within a household, the Campylobacter load in infant stool samples was positively correlated with the load in mother stool samples (r2 = 0.18) and soil collected inside the house (r2 = 0.36), which were in turn both correlated with Campylobacter loads in chicken and cattle feces (0.60 < r2 < 0.63) (P < 0.01). In conclusion, a high proportion of infants are infected with Campylobacter in eastern Ethiopia, and contact with the mother and contaminated soil may be associated with early infections. IMPORTANCE A high Campylobacter prevalence during early childhood has been associated with environmental enteric dysfunction (EED) and stunting, especially in low-resource settings. Our previous study demonstrated that Campylobacter was frequently found (88%) in children from eastern Ethiopia; however, little is known about potential Campylobacter reservoirs and transmission pathways leading to infection of infants by Campylobacter during early growth. In the longitudinal study presented here, Campylobacter was frequently detected in infants within the 106 surveyed households from eastern Ethiopia, and the prevalence was age dependent. Furthermore, preliminary analyses highlighted the potential role of the mother, soil, and livestock in the transmission of Campylobacter to the infant. Further work will explore the species and genetic composition of Campylobacter in infants and putative reservoirs using PCR and whole-genome and metagenomic sequencing. The findings from these studies can lead to the development of interventions to minimize the risk of transmission of Campylobacter to infants and, potentially, EED and stunting.

Chest X-ray predicts cases of pulmonary tuberculosis among women of reproductive age with acute respiratory symptoms: A multi-center cross-sectional study.

Background: Tuberculosis (TB) prevalence is increasing among women of reproductive age (WRA) in sub-Saharan Africa, yet undiagnosed and untreated cases remain rather high with serious health and socio-economic consequences. We aimed to assess the prevalence and predictors of TB in WRA seeking health care for acute respiratory symptoms. Methods: We consecutively enrolled outpatient WRA with acute respiratory symptoms seeking care at four healthcare facilities in Ethiopia between July 2019 and December 2020. Data on sociodemographic characteristics and clinical information were collected using a structured questionnaire administered by trained nurses. Posteroanterior chest X-ray was performed in non-pregnant WRA and interpreted independently by two radiologists. Sputum samples were collected from all patients and tested for pulmonary TB using Xpert MTB/RIF and/or smear microscopy. Predictors of bacteriologically confirmed TB cases were determined using binary logistic regression, with clinically relevant variables included in the final Firth's multivariate-penalized logistic regression model. Results: We enrolled 577 participants, of whom 95 (16%) were pregnant, 67 (12%) were living with HIV, 512 (89%) had cough of less than 2 weeks, and 56 (12%) had chest-x-ray findings suggestive of TB. The Overall prevalence of TB was 3% (95% CI: 1.8%-4.7%) with no significant difference observed between patient groups categorized by duration of cough or HIV serostatus (P-value = 0.9999). In multivariable analysis, TB-suggestive CXR abnormality (AOR 18.83 [95% CI, 6.20-57.18]) and history of weight loss (AOR 3.91 [95% CI, 1.25-12.29]) were associated with bacteriologically-confirmed TB cases. Conclusions: We found a high TB prevalence among low-risk women of reproductive age with acute respiratory symptoms. Routine CXR may improve early case detection and thereby TB treatment outcomes.

Implementation of evidence-based multiple focus integrated intensified TB screening to end TB (EXIT-TB) package in East Africa: a qualitative study.

INTRODUCTION: Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care. OBJECTIVE: We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up. METHODS: A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed. RESULTS: The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma. CONCLUSION: The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.

System and facility readiness assessment for conducting active surveillance of adverse events following immunization in Addis Ababa, Ethiopia.

BACKGROUND: To help distinguish vaccine-related adverse events following immunization (AEFI) from coincidental occurrences, active vaccine pharmacovigilance (VP) prospective surveillance programs are needed. From February to May 2021, we assessed the system and facility readiness for implementing active AEFI VP surveillance in Addis Ababa, Ethiopia. METHODS: Selected hospitals were assessed using a readiness assessment tool with scoring measures. The site assessment was conducted via in-person interviews within the specific departments in each hospital. We evaluated the system readiness with a desk review of AEFI guidelines, Expanded Program for Immunization Guidelines and Ethiopian Food and Drug Administration and Ethiopian Public Health Institute websites. RESULTS: Of the hospitals in Addis Ababa, 23.1% met the criteria for our site assessment. During the system readiness assessment, we found that essential components were in place. However, rules, regulations and proclamations pertaining to AEFI surveillance were absent. Based on the tool, the three hospitals (A, B and C) scored 60.6% (94/155), 48.3% (75/155) and 40% (62/155), respectively. CONCLUSIONS: Only one of three hospitals assessed in our evaluation scored >50% for readiness to implement active AEFI surveillance. We also identified the following areas for improvement to ensure successful implementation: training, making guidelines and reporting forms available and ensuring a system that accommodates paper-based and electronic-based recording systems.

Patterns of childhood tuberculosis diagnosis in Ethiopia: A multicenter cross-sectional study.

Background: Children share 12% of the global 10 million people infected with tuberculosis (TB) each year. Closing case detection gap in children remains difficult, with 56% of all children and 65% under-five with TB missed each year. We aimed to assess the patterns of childhood TB diagnosis and underlying determinants in Ethiopia when different TB diagnostic platforms are applied. Methods: A multi-site, cross-sectional study was carried out in Ethiopia as part of the larger EXIT-TB study - evidence-based multiple focused integrated intensified TB screening package. Outpatient children aged ≤ 15 with cough of any duration seeking care at four healthcare facilities in Ethiopia were enrolled consecutively. Participants underwent sputum Xpert MTB/RIF and/or smear microscopy and posteroanterior chest X-ray (CXR), and their clinical and sociodemographic data were captured using a structured questionnaire. Data were analyzed using Stata version 23. Multiple regression model was computed to determine the factors that influence TB case detection, with a 95% confidence interval (CI) and p < 0.05 taken as statistically significant. Results: A total of 438 children were enrolled. Of these, 399 had CXR examination of which 55 (13.8%) were suggestive of TB, 270 had Xpert MTB/RIF testing of which 32 (11.9%) were positive, and AFB smear microscopy was done for 51 children of which 2 (3.9%) were positive. Febrile children were more likely to be diagnosed with pulmonary TB than those without fever [aPR = 1.3, 95% CI (1.1-1.4)], and those with a TB contact history were more likely to be diagnosed with pulmonary TB than those with no such contacts [aPR = 1.2, 95% CI (1.1-1.3)]. Children from rural residences were more likely to be diagnosed with TB than those from urban residences [aPR = 1.3, 95% CI (1.1-1.5)]. Conclusion: The findings showed that clinical diagnosis remains an important method of TB diagnosis in children and the preferred choice to avert underdiagnosis. A more sensitive TB diagnostic method for children was symptom screening, followed by CXR and Xpert MTB/RIF assay or smear microscopy. Hence, an algorithm that combines clinical, CXR, and microbiological confirmatory tests can improve the rate of pulmonary TB diagnosis in children till more accurate and cost-effective diagnostic tools are accessible. Fever, weight loss, and TB contact history are highly associated with TB positivity rates in children.

Rapid virtual training and field deployment for COVID-19 surveillance officers: experiences from Ethiopia.

Rapid scale-up of surveillance activities is the key to successful coronavirus disease 2019 (COVID-19) pandemic prevention and mitigation. Ethiopia did not have a sufficient number of active surveillance officers for the public health COVID-19 response. Training of surveillance officers was needed urgently to fill the gap in the workforce needed. Subject-matter experts from the United States and Ethiopia developed applicable training modules including background on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), contact investigation, and communications. The training modules were delivered live in real-time via web-based virtual presentation. Seventy-seven health surveillance officers were hired, trained, and deployed in two weeks to assist with surveillance activities in Ethiopia. Electronic capacity building is needed in order to improve Web-based training in resource-limited settings where internet access is limited or unreliable. Web-based synchronously delivered course was an effective platform for COVID-19 surveillance training. However, strengthening public and private information technology capacity, literacy, and internet availability will improve Web-based education platforms in resource-limited countries.

Joint Analysis of Phenotypic and Genomic Diversity Sheds Light on the Evolution of Xenobiotic Metabolism in Humans.

Variation in genes involved in the absorption, distribution, metabolism, and excretion of drugs (ADME) can influence individual response to a therapeutic treatment. The study of ADME genetic diversity in human populations has led to evolutionary hypotheses of adaptation to distinct chemical environments. Population differentiation in measured drug metabolism phenotypes is, however, scarcely documented, often indirectly estimated via genotype-predicted phenotypes. We administered seven probe compounds devised to target six cytochrome P450 enzymes and the P-glycoprotein (P-gp) activity to assess phenotypic variation in four populations along a latitudinal transect spanning over Africa, the Middle East, and Europe (349 healthy Ethiopian, Omani, Greek, and Czech volunteers). We demonstrate significant population differentiation for all phenotypes except the one measuring CYP2D6 activity. Genome-wide association studies (GWAS) evidenced that the variability of phenotypes measuring CYP2B6, CYP2C9, CYP2C19, and CYP2D6 activity was associated with genetic variants linked to the corresponding encoding genes, and additional genes for the latter three. Instead, GWAS did not indicate any association between genetic diversity and the phenotypes measuring CYP1A2, CYP3A4, and P-gp activity. Genome scans of selection highlighted multiple candidate regions, a few of which included ADME genes, but none overlapped with the GWAS candidates. Our results suggest that different mechanisms have been shaping the evolution of these phenotypes, including phenotypic plasticity, and possibly some form of balancing selection. We discuss how these contrasting results highlight the diverse evolutionary trajectories of ADME genes and proteins, consistent with the wide spectrum of both endogenous and exogenous molecules that are their substrates.

Quantifying intra- and inter-species contact rates at supplemental feeding sites in Ethiopia to inform rabies maintenance potential of multiple host species.

Rabies, a multi-host pathogen responsible for the loss of roughly 59,000 human lives each year worldwide, continues to impose a significant burden of disease despite control efforts, especially in Ethiopia. However, how species other than dogs contribute to rabies transmission throughout Ethiopia remains largely unknown. In this study, we quantified interactions among wildlife species in Ethiopia with the greatest potential for contributing to rabies maintenance. We observed wildlife at supplemental scavenging sites across multiple landscape types and quantified transmission potential. More specifically, we used camera trap data to quantify species abundance, species distribution, and intra- and inter-species contacts per trapping night over time and by location. We derived a mathematical expression for the basic reproductive number (R0 ) based on within- and between-species contract rates by applying the next generation method to the susceptible, exposed, infectious, removed model. We calculated R0 for transmission within each species and between each pair of species using camera trap data in order to identify pairwise interactions that contributed the most to transmission in an ecological community. We estimated which species, or species pairs, could maintain transmission ( R 0 > 1 ${R_0} > 1$ ) and which species, or species pairs, had contact rates too low for maintenance ( R 0 < 1 ${R_0} < 1$ ). Our results identified multiple urban carnivores as candidate species for rabies maintenance throughout Ethiopia, with hyenas exhibiting the greatest risk for rabies maintenance through intra-species transmission. Hyenas and cats had the greatest risk for rabies maintenance through inter-species transmission. Urban and peri-urban sites posed the greatest risk for rabies transmission. The night-time hours presented the greatest risk for a contact event that could result in rabies transmission. Overall, both intra- and inter-species contacts posed risk for rabies maintenance. Our results can be used to target future studies and inform population management decisions.

Unravelling the reservoirs for colonisation of infants with Campylobacter spp. in rural Ethiopia: protocol for a longitudinal study during a global pandemic and political tensions.

INTRODUCTION: Undernutrition is an underlying cause of mortality in children under five (CU5) years of age. Animal-source foods have been shown to decrease malnutrition in CU5. Livestock are important reservoirs for Campylobacter bacteria, which are recognised as risk factors for child malnutrition. Increasing livestock production may be beneficial for improving nutrition of children but these benefits may be negated by increased exposure to Campylobacter and research is needed to evaluate the complex pathways of Campylobacter exposure and infection applicable to low-income and middle-income countries. We aim to identify reservoirs of infection with Campylobacter spp. of infants in rural Eastern Ethiopia and evaluate interactions with child health (environmental enteric dysfunction and stunting) in the context of their sociodemographic environment. METHODS AND ANALYSIS: This longitudinal study involves 115 infants who are followed from birth to 12 months of age and are selected randomly from 10 kebeles of Haramaya woreda, East Hararghe zone, Oromia region, Ethiopia. Questionnaire-based information is obtained on demographics, livelihoods, wealth, health, nutrition and women empowerment; animal ownership/management and diseases; and water, sanitation and hygiene. Faecal samples are collected from infants, mothers, siblings and livestock, drinking water and soil. These samples are analysed by a range of phenotypic and genotypic microbiological methods to characterise the genetic structure of the Campylobacter population in each of these reservoirs, which will support inference about the main sources of exposure for infants. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Florida Internal Review Board (IRB201903141), the Haramaya University Institutional Health Research Ethics Committee (COHMS/1010/3796/20) and the Ethiopia National Research Ethics Review Committee (SM/14.1/1059/20). Written informed consent is obtained from all participating households. Research findings will be disseminated to stakeholders through conferences and peer-reviewed journals and through the Feed the Future Innovation Lab for Livestock Systems.

Validity of InterVA model versus physician review of verbal autopsy for tracking tuberculosis-related mortality in Ethiopia.

BACKGROUND: In most African countries where a legitimate vital registration system is lacking, physicians often review verbal autopsy (VA) data to determine the cause of death, while there are concerns about the routine practicality, accuracy, and reliability of this procedure. In Ethiopia where the burden of tuberculosis (TB) remains unacceptably high, reliable VA data are needed to guide intervention strategies. This study aimed to validate the InterVA model against the physician VA in tracking TB-related mortality in Ethiopia. METHODS: From a sample of deaths in Addis Ababa, Ethiopia, VAs were conducted on TB-related mortality, physician-certified verbal autopsy (PCVA) through multiple steps to ascertain the causes of death. InterVA model was used to interpret the causes of death. Estimates of TB-related deaths between physician reviews and the InterVA model were compared using Cohen's Kappa (k), Receiver-operator characteristic (ROC) curve analysis, sensitivity, and specificity to compare agreement between PCVA and InterVA. RESULTS: A total of 8952 completed PCVA were used. The InterVA model had an optimal likelihood cut-off point sensitivity of 0.64 (95% CI: 59.0-69.0) and specificity of 0.95 (95% CI: 94.9-95.8). The area under the ROC curve was 0.79 (95% CI: 0.78-0.81). The level of agreement between physician reviews and the InterVA model to identifying TB-related mortality was moderate (k = 0.59, 95% CI: 0.57-0.61). CONCLUSION: The InterVA model is a viable alternative to physician review for tracking TB-related causes of death in Ethiopia. From a public health perspective, InterVA helps to analyze the underlying causes of TB-related deaths cost-effectively using routine survey data and translate to policies and strategies in resource-constrained countries.

Conceptualising centres of excellence: a scoping review of global evidence.

OBJECTIVE: Globally, interest in excellence has grown exponentially, with public and private institutions shifting their attention from meeting targets to achieving excellence. Centres of Excellence (CoEs) are standing at the forefront of healthcare, research and innovations responding to the world's most complex problems. However, their potential is hindered by conceptual ambiguity. We conducted a global synthesis of the evidence to conceptualise CoEs. DESIGN: Scoping review, following Arksey and O'Malley's framework and methodological enhancement by Levac et al and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. DATA SOURCES: PubMed, Scopus, CINAHL, Google Scholar and the Google engine until 1 January 2021. ELIGIBILITY: Articles that describe CoE as the main theme. RESULTS: The search resulted in 52 161 potential publications, with 78 articles met the eligibility criteria. The 78 articles were from 33 countries, of which 35 were from the USA, 3 each from Nigeria, South Africa, Spain and India, and 2 each from Ethiopia, Canada, Russia, Colombia, Sweden, Greece and Peru. The rest 17 were from various countries. The articles involved six thematic areas-healthcare, education, research, industry, information technology and general concepts on CoE. The analysis documented success stories of using the brand 'CoE'-an influential brand to stimulate best practices. We identified 12 essential foundations of CoE-specialised expertise; infrastructure; innovation; high-impact research; quality service; accreditation or standards; leadership; organisational structure; strategy; collaboration and partnership; sustainable funding or financial mechanisms; and entrepreneurship. CONCLUSIONS: CoEs have significant scientific, political, economic and social impacts. However, there are inconsistent use and self-designation of the brand without approval by an independent, external process of evaluation and with high ambiguity between 'CoEs' and the ordinary 'institutions' or 'centres'. A comprehensive framework is needed to guide and inspire an institution as a CoE and to help government and funding institutions shape and oversee CoEs.

Who to Involve and Where to Start Integrating Tuberculosis Screening into Routine Healthcare Services: Positive Cough of Any Duration as the First Step for Screening Tuberculosis in Ethiopia.

BACKGROUND: Recent country surveys have shown an unacceptably high prevalence of confirmed tuberculosis (TB) even among those with a low duration of cough, and more than 50% of those with bacteriologically confirmed pulmonary tuberculosis (PTB) do not report symptoms that correspond to presumptive TB. Furthermore, there has been an increase in the incidence of smear-negative PTB patients who can serve as a source of infection. We investigated whether screening people who sought healthcare for cough of any duration can increase TB case detection in Ethiopia, and compiled the lessons learned and recommendations. METHODS: We carried out a facility-based study in Ethiopia. All consenting participants who sought any healthcare at the outpatients department, and healthcare facilities for reproductive and child health, anti-retroviral therapy, and diabetes were screened for cough of any duration, and those with cough underwent further investigations using chest radiography (CXR) (except for pregnant women, patients on anti-retroviral therapy, and diabetic patients) and microbiological tests. Confirmed cases were linked to TB treatment following the country's standard guidelines. RESULTS: We screened 195,713 people who sought healthcare for cough of any duration. Of these, 2647 reported cough symptom of any duration, of whom 1853 underwent further diagnostic tests as they fulfilled the criteria for presumptive TB. Overall, 309/1853 (16.7%) were diagnosed with PTB and linked to TB treatment. Screening by cough of any duration and/or CXR improved TB case finding, and engaging all health teams (administrative and supportive staff, as well as healthcare providers) in the TB screening and diagnosis significantly improved the process. CONCLUSION: Screening for TB using cough of any duration and/or CXR for any patient who sought healthcare has the potential to increase both the number of presumptive TB cases and the number of patients diagnosed with and treated for TB in Ethiopia. Such initiatives require strong engagement of facility staff, regular maintenance and calibration of TB diagnostic equipment, and uninterrupted reagent supplies.

Impact of early chest radiography on delay in pulmonary tuberculosis case notification in Ethiopia.

Background: One-third of tuberculosis (TB) cases are missed each year and delays in the diagnosis of TB are hampering the whole cascade of care. Early chest X-ray (CXR) in patients with cough irrespective of duration may reduce TB diagnostic and treatment delays and increase the number of TB patients put into TB care. We aimed to evaluate the impact of CXR on delay in the diagnosis of pulmonary tuberculosis (PTB) among people with cough of any duration. Methods: A facility-based cross-sectional study was conducted in four selected health facilities from two regions and two city administrations of Ethiopia. Patients who sought health care were screened for cough of any duration, and those with cough underwent CXR for PTB and their sputum specimens were tested for microbiological confirmation. Delays were followed up and calculated using median and inter-quartile range (IQR) to summarize (first onset of cough to first facility visit, ≥15 days), diagnosis delay (first facility visit to date of PTB diagnosis, >7 days), and total delay (first onset of cough to date of PTB diagnosis, >21 days). Kruskal-Wallis and Mann-Witney tests were used to compare the delays among independent variables. Results: A total of 309 PTB cases were consecutively diagnosed of 1853 presumptive TB cases recruited in the study that were identified from 2647 people who reported cough of any duration. The median (IQR) of patient delay, diagnosis delay, and the total delay was 30 (16-44), 1 (0-3), and 31 (19-48) days, respectively. Patients' delay contributed a great role in the total delay, 201/209 (96.2%). Median diagnosis delay was higher among those that visited health center, diagnosed at a facility that had no Xpert mycobacterium tuberculosis (MTB)/RIF assay, radiologist, or CXR (P < 0.05). Factors associated with patients delay were history of previous TB treatment (adjusted prevalence ratio [aPR] = 0.79, 95% confidence interval [CI]: 0.63-0.99) and history of weight loss (aPR = 1.12; 95% CI: 1.0-1.25). Early CXR screening for cough of <2 weeks duration significantly reduced the patients' delay and thus the total delay, but not diagnostic delay alone. Conclusion: Early screening using CXR minimized delays in the diagnosis of PTB among people with cough of any duration. Patients' delay was largest and contributed great role in the delay of TB cases. Screening by cough of any duration and/or CXR among people seeking healthcare along with ensuring the availability of Xpert MTB/RIF assay and skilled human power at primary healthcare facilities are important to reduce patient and diagnostic delays of PTB in Ethiopia.

Pharmacodynamic biomarkers for quantifying the mycobacterial effect of high doses of rifampin in patients with rifampin-susceptible pulmonary tuberculosis.

Background: Suboptimal drug exposure in patients with drug-susceptible tuberculosis (DS-TB) can drive treatment failure. Pharmacodynamics (PD) biomarkers such as the plasma TB drug-activity (TDA) assay may guide dose finding studies and predict microbiological outcomes differently than conventional indices. Methods: A study was nested from phase 2b randomized double-blind controlled trial of Tanzanian patients who received a 600 mg, 900 mg, or 1200 mg with a standard dose for DS-TB. Serum at 6 weeks collected over 24-h at 2-h intervals was collected for rifampin area under the concentration-time curve relative to minimum inhibitory concentration (AUC0-24/MIC) or peak concentration and MIC (Cmax/MIC). TDA was the ratio of time-to-positive growth of the patient's Mycobacterium tuberculosis isolates with and without coculture of patient's plasma collected at Cmax. Spearman's rank correlation (r) between PD parameters and culture convention on both liquid and solid culture media. Results: Among 10 patients, 600 mg (3), 900 mg (3), and 1200 mg (4) of rifampin dosages. The mean ± standard deviation (SD) of AUC0-24/MIC for patients on 600 mg was 168 ± 159 mg·h/L, on 900 mg was 169 ± 166 mg·h/L, and on 1200 mg was 308 ± 238 mg·h/L. The mean-TDA (SD) was 2.56 (±0.75), 1.5 (±0.59), and 2.29 (±1.08) for patients on 600 mg, 900 mg, and 1200 mg rifampin doses, respectively. Higher TDA values correlated with faster time to culture convention on both liquid (r = -0.55, P = 0.099) and solid media (r = -0.65, P = 0.04). Conclusions: TDA and rifampin AUC0-24/MIC did not trend as expected with rifampin dose, but TDA better predicted the time to sputum culture conversion. TDA may provide additional discrimination in predicting treatment response for some regimens distinct from plasma exposure relative to MIC or mg/kg dose.

Annual Tuberculosis Preventive Therapy for Persons With HIV Infection : A Randomized Trial.

BACKGROUND: Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain. OBJECTIVE: To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2 years versus once. DESIGN: Randomized trial. (ClinicalTrials.gov: NCT02980016). SETTING: South Africa, Ethiopia, and Mozambique. PARTICIPANTS: Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis. INTERVENTION: Participants were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture. MEASUREMENTS: Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months. RESULTS: Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]). LIMITATION: If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness. CONCLUSION: Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy. PRIMARY FUNDING SOURCE: The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.