Clinical profiles and mortality predictors of hospitalized patients with COVID-19 in Ethiopia.

BACKGROUND: Studying the characteristics of hospitalized Coronavirus Disease 2019 (COVID-19) patients is vital for understanding the disease and preparing for future outbreaks. The aim of this study was to analyze and describe the clinical profiles and factors associated with mortality among COVID-19 patients admitted to Jimma Medical Center COVID-19 Treatment Center (JMC CTC) in Ethiopia. METHODS: All confirmed COVID-19 patients admitted to JMC CTC between 17 April 2020 and 05 March 2022 were included in this study. Socio-demographic data, clinical information, and outcome variables were collected retrospectively from medical records and COVID-19 database at the hospital. Bivariable and multivariable analyses were performed to determine factors associated with COVID-19 severity and mortality. A P-value < 0.05 was considered statistically significant. RESULTS: A total of 542 confirmed COVID-19 patients were admitted to JMC CTC, of which 322 (59.4%) were male. Their median age was 48 years (IQR 32-64). About 51% (n = 277) of them had severe COVID-19 upon admission. Patients with hypertension [AOR: 2.8 (95% CI: 1.02-7.7, p = 0.046)], diabetes [AOR: 8.8 (95% CI: 1.2-17.3, p = 0.039)], and underlying respiratory diseases [AOR: 18.8 (95% CI: 2.06-71.51, p = 0.009)] were more likely to present with severe COVID-19 cases. Overall, 129 (23.8%) died in the hospital. Death rate was higher among patients admitted with severe disease [AHR = 5.5 (3.07-9.9) p < 0.001)] and those with comorbidities such as hypertension [AHR = 3.5 (2.28-5.41), p < 0.001], underlying respiratory disease [AHR = 3.4 (1.97-5.94), p < 0.001], cardiovascular disease (CVDs) [AHR = 2.8 (1.73-4.55), p < 0.001], and kidney diseases [AHR = 3.7 (2.3-5.96), p < 0.001]. CONCLUSION: About half of COVID-19 cases admitted to the hospital had severe disease upon admission. Comorbidities such as hypertension, diabetes, and respiratory diseases were linked to severe illness. COVID-19 admissions were associated with high inpatient mortality, particularly among those with severe disease and comorbidities.

Tailoring COVID-19 Vaccination Strategies in High-Seroprevalence Settings: Insights from Ethiopia.

This study aimed to retrospectively assess the cost-effectiveness of various COVID-19 vaccination strategies in Ethiopia. It involved healthcare workers (HCWs) and community participants; and was conducted through interviews and serological tests. Local SARS-CoV-2 variants and seroprevalence rates, as well as national COVID-19 reports and vaccination status were also analyzed. A cost-effectiveness analysis was performed to determine the most economical vaccination strategies in settings with limited vaccine access and high SARS-CoV-2 seroprevalence. Before the arrival of the vaccines, 65% of HCWs had antibodies against SARS-CoV-2, indicating prior exposure to the virus. Individuals with prior infection exhibited a greater antibody response to COVID-19 vaccines and experienced fewer new infections compared to those without prior infection, regardless of vaccination status (5% vs. 24%, p < 0.001 for vaccinated; 3% vs. 48%, p < 0.001 for unvaccinated). The cost-effectiveness analysis indicated that a single-dose vaccination strategy is optimal in settings with high underlying seroprevalence and limited vaccine availability. This study underscores the need for pragmatic vaccination strategies tailored to local contexts, particularly in high-seroprevalence regions, to maximize vaccine impact and minimize the spread of COVID-19. Implementing a targeted approach based on local seroprevalence information could have helped Ethiopia achieve higher vaccination rates and prevent subsequent outbreaks.

Haematological Indices in Acute Coronary Syndrome Patients in Ethiopia: A Comparative Cross-Sectional Study.

Background: Numerous biomarkers are used as diagnostic, prognostic, and predictive indicators of myocardial ischemia. The most commonly used biomarkers are cardiac troponin I (Tn-I) and creatinine kinase (CK-MB). However, in developing nations, their availability in primary care settings is extremely limited. In such situations, easily available assays such as complete blood count (CBC) should be investigated as prognostic indicators in individuals with acute coronary syndrome (ACS). Objective: This study aimed to compare the pattern of haematological indices and blood cell ratios of ACS patients compared with apparently healthy controls. Methods: Patients diagnosed with ACS were recruited consecutively between 01 May 2022 and 31 October 2023 at Jimma Medical Center (JMC). Biochemical analyses and complete blood counts were performed. Analysis of variance was performed to compare the continuous variables. Spearman correlation coefficient tests were performed to correlate hematologic parameters with high sensitive troponin-I (hs-Tn-I) levels. Results: This study enrolled 220 participants (110 patients with ACS and age, sex, and place of residence matched 110 non-ACS controls). From ACS group 99 (90%) were diagnosed with ST-elevated myocardial infarction. The ACS group had a significantly greater mean platelet volume (MPV), white blood cell count, red cell distribution width (RDW), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. The RDW (r = 0.248, p = 0.009) and MPV (r = 0.245, p = 0.009) were significantly positively correlated with hs-Tn-I levels in the ACS group. MPV, RDW, and monocyte count were significantly higher in non-survivor ACS patients (p <0.05). Conclusion: The significant differences observed in haematological parameters between individuals with ACS and healthy controls suggest the potential utility of these easily accessible and cost-effective diagnostics in predicting future morbidity and ACS risk. Incorporating these routine evaluations into clinical practice could enhance risk assessment and improve patient outcomes.

Long-term monitoring of SARS-CoV-2 seroprevalence and variants in Ethiopia provides prediction for immunity and cross-immunity.

Under-reporting of COVID-19 and the limited information about circulating SARS-CoV-2 variants remain major challenges for many African countries. We analyzed SARS-CoV-2 infection dynamics in Addis Ababa and Jimma, Ethiopia, focusing on reinfection, immunity, and vaccination effects. We conducted an antibody serology study spanning August 2020 to July 2022 with five rounds of data collection across a population of 4723, sequenced PCR-test positive samples, used available test positivity rates, and constructed two mathematical models integrating this data. A multivariant model explores variant dynamics identifying wildtype, alpha, delta, and omicron BA.4/5 as key variants in the study population, and cross-immunity between variants, revealing risk reductions between 24% and 69%. An antibody-level model predicts slow decay leading to sustained high antibody levels. Retrospectively, increased early vaccination might have substantially reduced infections during the delta and omicron waves in the considered group of individuals, though further vaccination now seems less impactful.

Associations of early childhood body mass index trajectories with body composition and cardiometabolic markers at age 10 years: the Ethiopian infant anthropometry and body composition (iABC) birth cohort study.

BACKGROUND: Variability in body mass index (BMI) (kg/m2) trajectories is associated with body composition and cardiometabolic markers in early childhood, but it is unknown how these associations track to later childhood. OBJECTIVES: We aimed to assess associations of BMI trajectories from 0 to 5 y with body composition and cardiometabolic markers at 10 y. METHODS: In the Ethiopian infant anthropometry and body composition (iABC) birth cohort, we previously identified 4 distinct BMI trajectories from 0 to 5 y: stable low BMI (19.2%), normal BMI (48.8%), rapid growth to high BMI (17.9%), and slow growth to high BMI (14.1%). At 10 y, we obtained data from 320 children on anthropometry, body composition, abdominal subcutaneous and visceral fat, and cardiometabolic markers. Associations of BMI trajectories and 10-y outcomes were analyzed using multiple linear regression. RESULTS: Compared with children with the normal BMI trajectory, those with rapid growth to high BMI had 1.7 cm (95% CI: 0.1, 3.3) larger waist circumference and those with slow growth to high had 0.63 kg/m2 (95% CI: 0.09, 1.17) greater fat mass index and 0.19 cm (95% CI: 0.02, 0.37) greater abdominal subcutaneous fat, whereas those with stable low BMI had -0.28 kg/m2 (95% CI: -0.59, 0.03) lower fat-free mass at 10 y. Although the confidence bands were wide and included the null value, children with rapid growth to high BMI trajectory had 48.6% (95% CI: -1.4, 123.8) higher C-peptide concentration and those with slow growth to high BMI had 29.8% (95% CI: -0.8, 69.8) higher insulin and 30.3% (95% CI: -1.1, 71.6) higher homeostasis model assessment of insulin resistance, whereas those with rapid growth to high BMI had -0.23 mmol/L (95% CI: -0.47, 0.02) lower total cholesterol concentration. The trajectories were not associated with abdominal visceral fat, blood pressure, glucose, and other lipids at 10 y. CONCLUSIONS: Children with rapid and slow growth to high BMI trajectories before 5 y tend to show higher measures of adiposity and higher concentrations of markers related to glucose metabolism at 10 y. CLINICAL TRIAL REGISTRY: ISRCTN46718296 (https://www.isrctn.com/ISRCTN46718296).

Health research mentorship in low-income and middle-income countries: a global qualitative evidence synthesis of data from a crowdsourcing open call and scoping review.

INTRODUCTION: Research mentorship is critical for advancing science, but there are few practical strategies for cultivating mentorship in health research resource-limited settings. WHO/TDR Global commissioned a group to develop a practical guide on research mentorship. This global qualitative evidence synthesis included data from a crowdsourcing open call and scoping review to identify and propose strategies to enhance research mentorship in low/middle-income country (LMIC) institutions. METHODS: The crowdsourcing open call used methods recommended by WHO/TDR and solicited descriptions of strategies to enhance research mentorship in LMICs. The scoping review used the Cochrane Handbook and predefined the approach in a protocol. We extracted studies focused on enhancing health research mentorship in LMICs. Textual data describing research mentorship strategies from the open call and studies from the scoping review were coded into themes. The quality of evidence supporting themes was assessed using the Confidence in the Evidence from Reviews of Qualitative research approach. RESULTS: The open call solicited 46 practical strategies and the scoping review identified 77 studies. We identified the following strategies to enhance research mentorship: recognising mentorship as an institutional responsibility that should be provided and expected from all team members (8 strategies, 15 studies; moderate confidence); leveraging existing research and training resources to enhance research mentorship (15 strategies, 49 studies; moderate confidence); digital tools to match mentors and mentees and sustain mentorship relations over time (14 strategies, 11 studies; low confidence); nurturing a culture of generosity so that people who receive mentorship then become mentors to others (7 strategies, 7 studies; low confidence); peer mentorship defined as informal and formal support from one researcher to another who is at a similar career stage (16 strategies, 12 studies; low confidence). INTERPRETATION: Research mentorship is a collective institutional responsibility, and it can be strengthened in resource-limited institutions by leveraging already existing resources. The evidence from the crowdsourcing open call and scoping review informed a WHO/TDR practical guide. There is a need for more formal research mentorship programmes in LMIC institutions.

Genomic analysis of Plasmodium vivax describes patterns of connectivity and putative drivers of adaptation in Ethiopia.

Ethiopia has the greatest burden of Plasmodium vivax in Africa, but little is known about the epidemiological landscape of parasites across the country. We analysed the genomic diversity of 137 P. vivax isolates collected nine Ethiopian districts from 2012 to 2016. Signatures of selection were detected by cross-country comparisons with isolates from Thailand (n = 104) and Indonesia (n = 111), representing regions with low and high chloroquine resistance respectively. 26% (35/137) of Ethiopian infections were polyclonal, and 48.5% (17/35) of these comprised highly related clones (within-host identity-by-descent > 25%), indicating frequent co-transmission and superinfection. Parasite gene flow between districts could not be explained entirely by geographic distance, with economic and cultural factors hypothesised to have an impact on connectivity. Amplification of the duffy binding protein gene (pvdbp1) was prevalent across all districts (16-75%). Cross-population haplotype homozygosity revealed positive selection in a region proximal to the putative chloroquine resistance transporter gene (pvcrt-o). An S25P variant in amino acid transporter 1 (pvaat1), whose homologue has recently been implicated in P. falciparum chloroquine resistance evolution, was prevalent in Ethiopia (96%) but not Thailand or Indonesia (35-53%). The genomic architecture in Ethiopia highlights circulating variants of potential public health concern in an endemic setting with evidence of stable transmission.

The Need to Establish and Sustain Public Health Emergency Operation Centers for Managing Infectious Disease Outbreaks: Lesson From Response to Louse-Borne Relapsing Fever Outbreak in Jimma, Ethiopia.

The coronavirus disease 2019 (COVID-19) pandemic has provided a great lesson for the globe about the necessity and significance of pandemics-related preparedness in all settings. Public health emergency operation centers play critical roles in preparing for and responding to public health events and emergencies by coordinating and pooling resources. In this article, we aimed to share lessons learnt from the public health response to the louse-borne relapsing fever (LBRF) outbreak coordinated by the emergency operation center established to respond to the COVID-19 pandemic in Jimma, Ethiopia.After the major waves of COVID-19 outbreaks in Ethiopia were over, Jimma University Medical Center (JUMC) reported clusters of louse-borne relapsing fever cases from Jimma Main Prison. Accordingly, Jimma Emergency Operation Center (JEOC) established for the COVID-19 pandemic was immediately alerted and effectively coordinated the overall response.As a result, the outbreak was contained within the prison without spreading to the community and the outbreak ended within a shorter period compared to previous LBRF outbreaks in Ethiopia. This indicates the necessity of establishing and sustaining public health emergency operation centers to prepare for and combat potential future public health emergencies.

Clinical performance validation of the STANDARD G6PD test: A multi-country pooled analysis.

INTRODUCTION: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. METHODS AND FINDINGS: Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%-85.4%) for females with intermediate activity between 30%-70%. Specificity was 98.1% (95% CI 97.6%-98.5%) and 92.8% (95% CI 91.6%-93.9%) for G6PD deficient individuals and intermediate females, respectively. Out of 20 G6PD intermediate females with false normal results, 12 had activity levels >60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test. CONCLUSIONS: The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Association of linear growth velocities between 0 and 6 years with kidney function and size at 10 years: A birth cohort study in Ethiopia.

BACKGROUND: Risk of noncommunicable diseases accrues from fetal life, with early childhood growth having an important role in adult disease risk. There is a need to understand how early-life growth relates to kidney function and size. OBJECTIVES: This study aimed to assess the association of linear growth velocities among children between 0 and 6 y with kidney function and size among children aged 10 y. METHODS: The Ethiopian Anthropometric and Body Composition birth cohort recruited infants born at term to mothers living in Jimma with a birth weight of ≥1500 g and without congenital malformations. Participants were followed up with 13 measurements between birth and 6 y of age. The latest follow-up was at ages 7-12 y with measurement of serum cystatin C as a marker of kidney function and ultrasound assessment of kidney dimensions. Kidney volume was computed using an ellipsoid formula. Linear-spline multilevel modeling was used to compute linear growth velocities between 0 and 6 y. Multiple linear regression modeling was used to examine the associations of linear growth velocities in selected age periods with cystatin C and kidney size. RESULTS: Data were captured from 355 children, at a mean age of 10 (range 7-12) y. The linear growth velocity was high between 0 and 3 mo and then decreased with age. There was no evidence of an association of growth velocity ≤24 mo with cystatin C at 10 y. Between 24 and 48 and 48 and 76 mo, serum cystatin C was higher by 2.3% [95% confidence interval (CI): 0.6, 4.2] and 2.1% (95% CI: 0.3, 4.0) for 1 SD higher linear growth velocity, respectively. We found a positive association between linear growth velocities at all intervals between 0 and 6 y and kidney volume. CONCLUSIONS: Greater linear growth between 0 and 6 y of development was positively associated with kidney size, and greater growth velocity after 2 y was associated with higher serum cystatin C concentrations.

Prevalence and predictors of asymptomatic malaria infection in Boricha District, Sidama Region, Ethiopia: implications for elimination strategies.

BACKGROUND: Malaria remains a major public health threat in Ethiopia despite the tremendous progress made towards the 2030 elimination targets. The silent transmission of asymptomatic infection is one of the factors that enhance the persistence of the disease as a public health issue and impedes efforts to eliminate malaria. Thus, this study aimed at investigating the prevalence and risk factors of asymptomatic malaria infection in Boricha district, Sidama region of Ethiopia. METHODS: A community-based cross-sectional study was conducted in eight selected kebeles (smallest administrative unit) in Boricha district. Representative households were chosen using a multi-stage sampling technique. A total of 573 participants were included in the study. Malaria diagnosis was performed using rapid diagnostic test (RDT) and microscopy. A structured questionnaire was administered to collect socio-demographic information. Epi data 3.1 was employed for data entry, and SPSS version 25 was used for analysis. RESULTS: Of the 573 asymptomatic participants tested, 6.1% were found to be positive by RDT and 4.0% by microscopy. Participants aged under 5 years (AOR = 1.57, 95% CI 0.46-5.39) and 5-14 years old (AOR = 2.42, 95% CI 1.08-5.40), Insecticide-treated net utilization (AOR = 8.41; 95% CI 1.09-65.08), travel history (AOR = 6.85, 95% CI 2.32-20.26) and living in a house with windows (AOR = 2.11, 95% CI 1.02-4.36) were significantly associated with the asymptomatic malaria infection. CONCLUSION: The findings of this study revealed that prevalence of asymptomatic malaria infection was higher in the study area. As a result, rigorous implementation of existing interventions, such as vector control and anti-malaria drugs, is strongly recommended. In addition, devising new ones that are suited to the contextual situations is highly suggested.

Effect of dolutegravir-based first-line antiretroviral therapy on weight and body mass index among adult people living with HIV on follow up at health facilities in Hawassa city administration, Southern Ethiopia: a retrospective cohort study.

BACKGROUND: The nature and burden of weight gain associated with antiretroviral treatment (ART) using a combination of Tenofovir disoproxil fumarate, lamivudine and dolutegravir (TLD) among people living with HIV (PLWH) has not been thoroughly investigated in Ethiopia. Therefore, this study aimed to evaluate changes in body weight and body mass index (BMI) in adults who initiated TLD or switched to TLD compared to those who received a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapies. METHODS: A retrospective cohort study was conducted among adult PLWH who had been receiving ART between February 2017 and October 2022 in Hawassa city administration, Sidama region. Linear mixed-effects model was used to examine BMI and body weight trends over time, while a binary logistic regression was performed to identify factors associated with a ≥ 10% weight gain. RESULTS: A total of 524 adult PLWH with a median age of 35 (interquartile range: 30-41) years were included. TLD-initiated arm experienced significantly greater mean weight (8.6 kg vs. 4.95 kg, p < 0.0001) and BMI (3.11 kg/m2 vs. 1.84 kg/m2, p < 0.0001) increase than the NNRTI-based arm at two years. However, the switched arm showed no significant difference in weight (5.6 kg) and BMI (2.13 kg/m2) compared to the NNRTI-based arm (p > 0.05). There was a significant interaction effect between ART regimens and time in predicting weight and BMI gain (p < 0.01). Initiating ART with TLD had higher odds of ≥10% body weight gain at two years (adjusted odds ratio [AOR]: 1.9; 95% CI: 1.19-3.04). Other baseline factors such as age ≥40 years (AOR: 2.02; 95% CI: 1.35-3.02), weight <50kg (AOR: 3.0; 95% CI: 1.86-4.84), advanced disease stages (AOR: 1.78; 95% CI: 1.1-2.86) and ambulatory-bedridden functional status (AOR: 2.0; 95% CI: 1.05-3.8) were also associated with ≥10% weight gain. CONCLUSION: Initiating ART with TLD was significantly associated with greater weight and BMI gain than the NNRTI-based regimens. Therefore, the cardio-metabolic implications of weight gain after the TLD initiation in this population should be monitored and thoroughly investigated.

A significant interaction effect was observed between ART regimens and time in predicting weight and BMI gain.Starting ART with TLD was associated with a significant weight gain and treatment-emergent overweight/obesity than the NNRTI-based therapies.ART initiating with TLD had 1.9 times higher odds of >10% body weight gain than the NNRTI-based therapies.

Severe Hemolysis during Primaquine Radical Cure of Plasmodium vivax Malaria: Two Systematic Reviews and Individual Patient Data Descriptive Analyses.

Primaquine (PQ) kills Plasmodium vivax hypnozoites but can cause severe hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We conducted two systematic reviews. The first used data from clinical trials to determine the variety of definitions and frequency of hematological serious adverse events (SAEs) related to PQ treatment of vivax malaria. The second used data from prospective studies and case reports to describe the clinical presentation, management, and outcome of severe PQ-associated hemolysis necessitating hospitalization. In the first review, SAEs were reported in 70 of 249 clinical trials. There were 34 hematological SAEs among 9,824 patients with P. vivax malaria treated with PQ, nine of which necessitated hospitalization or blood transfusion. Criteria used to define SAEs were diverse. In the second review, 21 of 8,487 articles screened reported 163 patients hospitalized after PQ radical cure; 79.9% of whom (123 of 154) were prescribed PQ at ≥ 0.5 mg/kg/day. Overall, 101 patients were categorized as having probable or possible severe PQ-associated hemolysis, 96.8% of whom were G6PD deficient (< 30% activity). The first symptoms of hemolysis were reported primarily on day 2 or 3 (45.5%), and all patients were hospitalized within 7 days of PQ commencement. A total of 57.9% of patients (77 of 133) had blood transfusion. Seven patients (6.9%) with probable or possible hemolysis died. Even when G6PD testing is available, enhanced monitoring for hemolysis is warranted after PQ treatment. Clinical review within the first 5 days of treatment may facilitate early detection and management of hemolysis. More robust definitions of severe PQ-associated hemolysis are required.

Associations of weight and body composition at birth with body composition and cardiometabolic markers in children aged 10 y: the Ethiopian infant anthropometry and body composition birth cohort study.

BACKGROUND: Although birth weight (BW) has been associated with later cardiovascular disease and type 2 diabetes, the role of birth fat mass (BFM) and birth fat-free mass (BFFM) on cardiometabolic health is unclear. OBJECTIVES: To examine associations of BW, BFM, and BFFM with later anthropometry, body composition, abdominal fat, and cardiometabolic markers. METHODS: Birth cohort data on standardized exposure variables (BW, BFM, and BFFM) and follow-up information at age 10 y on anthropometry, body composition, abdominal fat, and cardiometabolic markers were included. A linear regression analysis was used to assess associations of exposures with outcome variables, adjusting for maternal and child characteristics at birth and current body size in separate models. RESULTS: Among 353 children, mean (SD) age was 9.8 (1.0) y, and 51.5% were boys. In the fully adjusted model, 1-SD higher BW and BFFM were associated with 0.81 cm (95% CI: 0.21, 1.41 cm) and 1.25 cm (95% CI: 0.64, 1.85 cm) greater height at 10 y, respectively. The 1-SD higher BW and BFM were associated with 0.32 kg/m2 (95% CI: 0.14, 0.51 kg/m2) and 0.42 kg/m2 (95% CI: 0.25, 0.59 kg/m2) greater fat mass index at 10 y, respectively. In addition, 1-SD higher BW and BFFM were associated with 0.22 kg/m2 (95% CI: 0.09, 0.34 kg/m2) greater FFM index, whereas a 1-SD greater BFM was associated with a 0.05 cm greater subcutaneous adipose tissue (95% CI: 0.01, 0.11 cm). Furthermore, 1-SD higher BW and BFFM were associated with 10.3% (95% CI: 1.4%, 20.0%) and 8.3% (95% CI: -0.5%, 17.9%) greater insulin, respectively. Similarly, 1-SD higher BW and BFFM were associated with 10.0% (95% CI: 0.9%, 20.0%) and 8.5% (95% CI: -0.6%, 18.5%) greater homeostasis model assessment of insulin resistance, respectively. CONCLUSIONS: BW and BFFM rather than BFM are predictors of height and FFM index at 10 y. Children with higher BW and BFFM showed higher insulin concentrations and homeostasis model assessment of insulin resistance at 10 y of age. This trial was registered at ISRCTN as ISRCTN46718296.

Escalating spread of SARS-CoV-2 infection after school reopening among students in hotspot districts of Oromia Region in Ethiopia: Longitudinal study.

BACKGROUND: COVID-19 pandemic caused by extended variants of SARS-CoV-2 has infected more than 350 million people, resulting in over 5.5 million deaths globally. However, the actual burden of the pandemic in Africa, particularly among children, remains largely unknown. We aimed to assess the seroepidemiological changes of SARS-CoV-2 infection after school reopening among school children in Oromia, Ethiopia. METHODS: A prospective cohort study involving students aged 10 years and older were used. A serological survey was performed twice, at school reopening in December 2020 and four months later in April 2021. Participants were selected from 60 schools located in 15 COVID-19 hotspot districts in Oromia Region. Serology tests were performed by Elecsys anti-SARS-CoV-2 nucleocapsid assay. Data were collected using CSentry CSProData Entry 7.2.1 and exported to STATA version 14.2 for data cleaning and analysis. RESULTS: A total of 1884 students were recruited at baseline, and 1271 completed the follow-up. SARS-CoV-2 seroprevalence almost doubled in four months from 25.7% at baseline to 46.3% in the second round, with a corresponding seroincidence of 1910 per 100,000 person-week. Seroincidence was found to be higher among secondary school students (grade 9-12) compared to primary school students (grade 4-8) (RR = 1.6, 95% CI 1.21-2.22) and among those with large family size (> = 5) than those with a family size of <3 (RR = 2.1, 95% CI 1.09-4.17). The increase in SARS-CoV-2 seroprevalence among the students corresponded with Ethiopia's second wave of the COVID-19 outbreak. CONCLUSION: SARS-CoV-2 seroprevalence among students in hotspot districts of the Oromia Region was high even at baseline and almost doubled within four months of school recommencement. The high seroincidence coincided with the second wave of the COVID-19 outbreak in Ethiopia, indicating a possible contribution to school opening for the new outbreak wave.

Adapting international clinical trials during COVID-19 and beyond.

BACKGROUND: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration. THE NEW WORKING MODEL: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for good clinical practice, the development of a library of study-specific training videos, and interactive virtual training sessions, including practical laboratory-focused training sessions. We also report changes from in-person monitoring to remote monitoring as well as the development of a more localized network of clinical trial monitors to support hybrid models with in-person and remote monitoring depending on identified risks at each site. We established a virtual network across different trial and study sites with the objective to further build capacity for good clinical practice-compliant antimalarial trials and foster cross-country and cross-study site collaboration. CONCLUSION: The forced adaptation of these new strategies has come with advantages that we did not envisage initially. This includes improved, more frequent engagement through the established network with opportunities for increased south-to-south support and a substantially reduced carbon footprint and budget savings. Our new approach is challenging for study sites with limited prior experience but this can be overcome with hybrid models. Capacity building for laboratory-based work remains difficult using a virtual environment. The changes to our working model are likely to last, even after the end of the pandemic, providing a more sustainable and equitable approach to our research.

Efficacy, Safety, Tolerability, and Pharmacokinetics of MMV390048 in Acute Uncomplicated Malaria.

An open label, phase IIa study conducted in Ethiopia evaluated the efficacy, safety, tolerability, and pharmacokinetics of a single 120-mg dose of the phosphatidylinositol 4-kinase inhibitor MMV390048 in Plasmodium vivax malaria. The study was not completed for operational reasons and emerging teratotoxicity data. For the eight adult male patients enrolled, adequate clinical and parasitological response at day 14 (primary endpoint) was 100% (8/8). Asexual parasites and gametocytes were cleared in all patients by 66 and 78 hours postdose, respectively. There were two recurrent P. vivax infections (days 20 and 28) and a new Plasmodium falciparum infection (day 22). MMV390048 exposure in P. vivax patients was lower than previously observed for healthy volunteers. Mild adverse events, mainly headache and gastrointestinal symptoms, were reported by eight patients. Single-dose MMV390048 (120 mg) rapidly cleared asexual parasites and gametocytes in patients with P. vivax malaria and was well tolerated.