Molecular characterization of carbapenemase and extended spectrum beta-lactamase producing Acinetobacter baumannii isolates causing surgical site infections in Ethiopia.

BACKGROUND: Acinetobacter baumannii is an opportunistic pathogen that can cause a variety of nosocomial infections in humans. This study aimed to molecularly characterize extended-spectrum beta-lactamase (ESBL) producing and carbapenem-resistant Acinetobacter species isolated from surgical site infections (SSI). METHODS: A multicentre cross-sectional study was performed among SSI patients at four hospitals located in Northern, Southern, Southwest, and Central parts of Ethiopia. The isolates were identified by microbiological methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibility was determined using disk diffusion. The presence of phenotypic ESBL and carbapenemase production was detected by employing standard microbiological tests, including combined disk diffusion (CDT). ESBL and carbapenem resistance determinants genes were studied by polymerase chain reaction (PCR) and sequencing. RESULTS: A total of 8.7% Acinetobacter species were identified from 493 culture-positive isolates out of 752 SSI wounds. The species identified by MALDI-TOF MS were 88.4% A. baumannii, 4.7% Acinetobacter pittii, 4.7% Acinetobacter soli, and 2.3% Acinetobacter lactucae. Of all isolates 93% were positive for ESBL enzymes according to the CDT. Using whole genome sequencing 62.8% of the A. baumannii harbored one or more beta-lactamase genes, and 46.5% harbored one or more carbapenemase producing genes. The distribution of beta-lactamases among Acinetobacter species by hospitals was 53.8%, 64.3%, 75%, and 75% at JUSH, TASH, DTCSH, and HUCSH respectively. Among ESBL genes, blaCTX-M alleles were detected in 21.4% of isolates; of these 83.3% were blaCTX-M-15. The predominant carbapenemase gene of blaOXA type was detected in 24 carbapenem-resistant A. baumannii followed by blaNDM alleles carried in 12 A. baumannii with blaNDM-1 as the most common. CONCLUSIONS: The frequency of Acinetobacter species that produce metallobetalactamases (MBLs) and ESBLs that were found in this study is extremely scary and calls for strict infection prevention and control procedures in health facilities helps to set effective antibiotics stewardship.

Strengthening implementation of integrated care for small and nutritionally at-risk infants under six months and their mothers: Pre-trial feasibility study.

An integrated care pathway to manage small and nutritionally at-risk infants under 6 months (u6m) and their mothers (MAMI Care Pathway) is consistent with 2023 WHO malnutrition guidelines and is being tested in a randomised controlled trial (RCT) in Ethiopia. To optimise trial implementation, we investigated contextual fit with key local stakeholders. We used scenario-based interviews with 17 health workers and four district managers to explore perceived feasibility. Eighteen policymakers were also surveyed to explore policy coherence, demand, acceptability, evidence needs, opportunities and risks. The Bowen feasibility framework and an access to health care framework were adapted and applied. Health workers perceived the MAMI Care Pathway as feasible to implement with support to access services and provide care. The approach is acceptable, given consistency with national policies, local protocols and potential to improve routine care quality. Demand for more comprehensive, preventive and person-centred outpatient care was driven by concerns about unmet, hidden and costly care burden for health services and families. Inpatient care only for severe wasting treatment is inaccessible and unacceptable. Support for routine and expanded components, especially maternal mental health, is needed for successful implementation. Wider contextual factors may affect implementation fidelity and strength. Policymakers cautiously welcomed the approach, which resonates with national commitments, policies and plans but need evidence on how it can work within varied, complex contexts without further system overstretch. A responsive, pragmatic randomised controlled trial will generate the most useful evidence for policymakers. Findings have informed trial preparation and implementation, including a realist evaluation to contextualise outcomes.

Bacterial profile of surgical site infection and antimicrobial resistance patterns in Ethiopia: a multicentre prospective cross-sectional study.

BACKGROUND: Globally, surgical site infections (SSI) are the most commonly reported healthcare-associated infections. METHODS: A multicentre study was conducted among patients who underwent surgical procedures at four hospitals located in Northern (Debre Tabor), Southern (Hawassa), Southwest (Jimma), and Central (Tikur Anbessa) parts of Ethiopia. A total of 752 patients clinically studied for surgical site infection were enrolled. The number of patients from Debre Tabor, Hawassa, Jimma, and Tikur Anbessa, hospitals was 172, 184, 193, and 203, respectively. At each study site, SSI discharge culture was performed from all patients, and positive cultures were characterized by colony characteristics, Gram stain, and conventional biochemical tests. Each bacterial species was confirmed using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI TOF). An antimicrobial susceptibility test (AST) was done on Mueller-Hinton agar using the disk diffusion method. Logistic regression analysis was used to assess associations of dependent and independent variables. A p-value < 0.05 was considered statistically significant. Data were analysed using STATA 16 software. RESULTS: Among 752 wound discharge cultures performed, 65.5% yielded growth. Among these, 57.9% and 42.1% were Gram-negative and Gram-positive isolates, respectively. In this study, a total of 494 bacteria were isolated; Staphylococcus aureus (31%), Escherichia coli (20.7%), and Klebsiella pneumoniae (9.8%) were the most common. Rare isolates (0.8% each) included Raoultella ornithinolytica, Stenotrophomonas maltophilia, Alcalignes faecalis, Pantoea ecurina, Bacillus flexus, and Paenibacillus tylopili. Enterobacteriaceae showed high levels of resistance to most of the tested antibiotics but lower levels of ertapenem (32.9%), amikacin (24.3%), imipenem (20.3%), and meropenem (17.6%) resistance. Multidrug-resistant (MDR) frequency of Enterobacteriaceae at Debre Tabor, Hawassa, Jimma, and Tikur Anbessa hospitals was 84.5%, 96.5%, 97.3%, and 94%, respectively. Ages ≥ 61 years (AOR = 2.83, 95% CI: 1.02-7.99; P 0.046), prolonged duration of hospital stay (AOR = 4.15, 95% CI: 2.87-6.01; P 0.000), history of previous antibiotics use (AOR = 2.83, 95% CI: 1.06-2.80; P 0.028), history of smoking (AOR = 2.35, 95% CI: 1.44-3.83; P 0.001), emergency surgery (AOR = 2.65, 95% CI: 1.92-3.66; P 0.000), and duration of operation (AOR = 0.27, 95% CI: 0.181-0.392; P 0.000) were significant risk factors. CONCLUSION: The most prevalent isolates from Gram-positive and Gram-negative bacteria across all hospitals were S. aureus and E. coli, respectively. Many newly emerging Gram-negative and Gram-positive bacteria were identified. Variation between hospitals was found for both SSI etiology type and MDR frequencies. Hence, to prevent the emergence and spread of MDR bacteria, standard bacteriological tests and their AST are indispensable for effective antimicrobial stewardship.

Contribution of the World Health Organization/ the special program for research and training in tropical disease (WHO/TDR's) in institution building: lessons from Ethiopia.

BACKGROUND: World Health Organization/Tropical Disease Research (WHO/TDR) has enduring investment in transfers of skills critical to sustaining resilient health research systems through postgraduate training, clinical research and development fellowship (CRDF), bioethics, and grants to neglected tropical disease research. TDR has a long history of partnership with Armauer Hansen Research Institute (AHRI) in Ethiopia. The collaboration started with individuals and lead to institution survival and success. Therefore, the purpose of this study was to explore the impact and lessons learned of TDR initiatives in Ethiopia. METHOD: This study was guided by the 'TDR Impact Pathways'. A total of thirteen in-depth, and five key informant interviews were conducted with individuals who are currently working in Addis Ababa, Gondar, Jimma Universities and AHRI. In addition to the interviews, reports, written communications and publications were reviewed. Interviews were audio recorded, transcribed verbatim, inductively coded, and analyzed thematically. The results were presented following the themes with supportive verbatim quotes. CONCLUSION: TDR's seed grants, training opportunities and technical support catalyzed individual, institutional and national research capacity in Ethiopia. This is a useful indication of how long-term collaboration between individuals could have broader institutional implication as evidenced from the TDR-AHRI complementary partnership.

Prevalence and assemblage of Giardia duodenalis in a case-control study of children under 5 years from Jimma, Southwest Ethiopia.

Giardia duodenalis is a common pathogenic intestinal protozoan parasite with high prevalence in developing countries, especially among children. The distribution of giardia assemblages among humans and their clinical relevance remains controversial. This study aimed to determine the prevalence and assemblage of Giardia among children under 5 years of age in Jimma, Southwest Ethiopia. Employing a case-control design, 606 children presenting with diarrhea at Jimma university medical center and Serbo Health Center were enrolled from December 2016 to July 2018 along with 617 matched controls without diarrhea. Giardia was detected and typed using real-time PCR. Univariate and multivariate regression analysis was performed. The total prevalence of Giardia was 41% (501/1223) and did not differ significantly between cases and controls (40% vs 42%). Prevalence increased by age, with the highest prevalence seen in children aged ≥ 25 months. Children without diarrhea with a history of diarrhea during the last month were more likely to be Giardia positive compared to children with no history diarrhea (OR 1.8 and 95%CI; 1.1-2.9). Regardless of current diarrhea symptoms, assemblage B predominated with 89%, followed by assemblage A (8%) and mixed infection assemblage A and B (3%). We report a high prevalence of Giardia by PCR detection in Jimma, Ethiopia, with assemblage B being predominant. There was a similar distribution of Giardia assemblages between children with and without diarrhea. Increasing age was a risk factor for Giardia infection. Community-based prevention and control strategies need to be employed to decrease the risk of giardia infection.

Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. METHODS: This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS: In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS: Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167 .).

High seroprevalence of anti-SARS-CoV-2 antibodies among Ethiopian healthcare workers.

BACKGROUND: COVID-19 pandemic has a devastating impact on the economies and health care system of sub-Saharan Africa. Healthcare workers (HWs), the main actors of the health system, are at higher risk because of their occupation. Serology-based estimates of SARS-CoV-2 infection among HWs represent a measure of HWs' exposure to the virus and could be used as a guide to the prevalence of SARS-CoV-2 in the community and valuable in combating COVID-19. This information is currently lacking in Ethiopia and other African countries. This study aimed to develop an in-house antibody testing assay, assess the prevalence of SARS-CoV-2 antibodies among Ethiopian high-risk frontline HWs. METHODS: We developed and validated an in-house Enzyme-Linked Immunosorbent Assay (ELISA) for specific detection of anti-SARS-CoV-2 receptor binding domain immunoglobin G (IgG) antibodies. We then used this assay to assess the seroprevalence among HWs in five public hospitals located in different geographic regions of Ethiopia. From consenting HWs, blood samples were collected between December 2020 and February 2021, the period between the two peaks of COVID-19 in Ethiopia. Socio-demographic and clinical data were collected using questionnaire-based interviews. Descriptive statistics and bivariate and multivariate logistic regression were used to determine the overall and post-stratified seroprevalence and the association between seropositivity and potential risk factors. RESULTS: Our successfully developed in-house assay sensitivity was 100% in serum samples collected 2- weeks after the first onset of symptoms whereas its specificity in pre-COVID-19 pandemic sera was 97.7%. Using this assay, we analyzed a total of 1997 sera collected from HWs. Of 1997 HWs who provided a blood sample, and demographic and clinical data, 51.7% were females, 74.0% had no symptoms compatible with COVID-19, and 29.0% had a history of contact with suspected or confirmed patients with SARS-CoV-2 infection. The overall seroprevalence was 39.6%. The lowest (24.5%) and the highest (48.0%) seroprevalence rates were found in Hiwot Fana Specialized Hospital in Harar and ALERT Hospital in Addis Ababa, respectively. Of the 821 seropositive HWs, 224(27.3%) of them had a history of symptoms consistent with COVID-19 while 436 (> 53%) of them had no contact with COVID-19 cases as well as no history of COVID-19 like symptoms. A history of close contact with suspected/confirmed COVID-19 cases is associated with seropositivity (Adjusted Odds Ratio (AOR) = 1.4, 95% CI 1.1-1.8; p = 0.015). CONCLUSION: High SARS-CoV-2 seroprevalence levels were observed in the five Ethiopian hospitals. These findings highlight the significant burden of asymptomatic infection in Ethiopia and may reflect the scale of transmission in the general population.

Retention on antiretroviral therapy in person with HIV and viral hepatitis coinfection in Ethiopia: a retrospective cohort study.

BACKGROUND: HIV coinfection with viral hepatitis B (HBV) or viral hepatitis C (HCV) is not uncommon in Ethiopia. Although the coinfections are presumed to interfere with antiretroviral treatment (ART), this is not widely studied in Sub-Saharan African settings. This study was conducted to determine ART retention in persons coinfected with HIV + HBV or HIV + HCV. METHODS: We reviewed the medical records of HIV-positive adults who initiated ART between 2011 to 2018 in four high-burden hospitals of Addis Ababa. Retention in care was the primary outcome of the study, which was compared between HIV and either HBV or HCV coinfected persons, and HIV-monoinfected persons. A parametric Gompertz regression model was used to compare retention between the coinfected and monoinfected groups. RESULTS: A total of 132 coinfected persons and 514 HIV-monoinfected individuals who initiated ART in 2011-2018 were compared. At 12-months of follow-up, 81.06% [95% CI: 73.3-86.9%] of the coinfected and 86.96% [95% CI: 83.7-89.6%] of the monoinfected were still on ART care. Cumulative retention in the coinfected group was 68.93% [60.4-76.3%] versus 80.35% [76.6-83.5%, p = 0.0048] in the monoinfected group. The cumulative retention was lower (61.25, 95% CI: 49.9-71.4%) in male coinfected patients than male monoinfected patients (77.77, 95% CI: 71.8-82.7%, p = 0.0041). In contrast, cumulative retention was similar in females in the coinfected group (80.76, 95% CI:67.3-89.5%) versus the monoinfected group (82.29, 95% CI:77.4-86.3%, p = 0.792). Overall, HIV-positive with viral hepatitis coinfection were 24 and 31% less likely to still be on ART care than the monoinfected group at 12 months and overall, with sub-distribution adjusted hazard ratio (AHR) of 0.76(95% CI:0.61-0.96, p = 0.021) and 0.69(95% CI:0.54-0.87, p = 0.002) respectively. CONCLUSIONS: We observed that coinfected individuals are less likely to stay on ART than HIV monoinfected individuals. The low retention in the coinfected group from this study may affect the success of survival gained in people living with HIV (PLHIV) in the long term. More concerted efforts need to be made to retain coinfected individuals at least at the level of monoinfected persons on long-term ART care. Future studies are needed to better understand the difference in retention, preferable in a prospective manner.

Predictors of glucose metabolism and blood pressure among Ethiopian individuals with HIV/AIDS after one-year of antiretroviral therapy.

OBJECTIVE: Better understanding of glucose metabolism in patients with HIV after initiating antiretroviral therapy (ART) is important to target treatment and follow-up for diabetes risk and other non-communicable diseases in resource-limited settings. The aim of this study was to assess the changes and predictors of glucose metabolism and blood pressure among patients with HIV on ART for 12 months. METHODS: One-year follow-up of Ethiopian patients with HIV after initiation of ART was done. Outcomes were changes in fasting plasma glucose (FPG), and 30-minute (30mPG) and 2-hour plasma glucose (2hPG) after oral glucose tolerance test, glycated haemoglobin (HbA1c), fasting plasma insulin (p-insulin), homeostatic model assessment index for insulin resistance (HOMA-IR) and blood pressure.   RESULTS: The mean age was 33 years, and the majority were women. During the first 12 months, levels of all plasma glucose parameters decreased, while p-insulin (10B 3.1; 95% CI2.4, 4.0), HOMA-IR (10B 3.1; 95% CI2.3, 4.0) and systolic blood pressure (B 4.0; 95% CI2.5, 5.5) increased. Fat-free mass at baseline predicted higher increments in p-insulin, HOMA-IR and blood pressure; whereas, fat mass predicted higher increment in HbA1c. CONCLUSIONS: Among Ethiopian patients with HIV, blood pressure and insulin increased, and all glucose parameters declined during 12-month of ART. Only longer-term follow-up will tell us whether insulin increase is due to insulin resistance or from recovering ß-cells.

Efficacy and safety of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Regular monitoring of anti-malarial drug efficacy is vital for establishing rational malaria treatment guidelines and ensuring adequate treatment outcomes. This study aimed to synthesize the available evidence on the efficacy of artemether-lumefantrine for the management of uncomplicated falciparum malaria in Ethiopia. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Relevant published studies were searched from the databases (PubMed, Google Scholar and Clinical trial registry) on published artemether-lumefantrine therapeutic efficacy studies conducted in Ethiopia from 2004 to 2020. The retrieved studies were assessed for quality using the modified Newcastle Ottawa Scale for observational studies and modified Jadad scale for interventional studies. Risk of bias was also assessed by using ROBINS-I tool. OpenMeta-Analyst software was used for the statistical analysis. The review protocol is registered in PROSPERO, number CRD42020201859. RESULTS: Fifteen studies (1523 participants) were included in the final analysis. The overall PCR-uncorrected pooled proportion of treatment success of artemether-lumefantrine therapy for uncomplicated falciparum malaria was 98.4% (95%CI 97.6-99.1). A random-effects model was used because of considerable heterogeneity [χ2 = 20.48, df (14), P = 0.011 and I2 = 31.65]. PCR-corrected pooled proportion of treatment success of artemether-lumefantrine therapy was 98.7% (95% CI 97.7-99.6). A random-effects model was used [χ2 = 7.37, df(6), P = 0.287 and I2 = 18.69]. Most studies included in the present review achieved a rapid reduction of fevers and parasitaemia between D0 and D3 of assessment. Adverse events were mostly mild and only two cases were reported as serious, but were not directly attributed to the drug. CONCLUSION: The present meta-analysis suggests that artemether-lumefantrine therapy is efficacious and safe in treating uncomplicated falciparum malaria in Ethiopia. However, owing to the high risk of bias in the included studies, strong conclusions cannot be drawn. Further high-quality RCTs assessing anti-malarial efficacy and safety should be performed to demonstrates strong evidence of changes in parasite sensitivity to artemether-lumefantrine in Ethiopia.

Social, economic and cultural influences on adolescent nutrition and physical activity in Jimma, Ethiopia: perspectives from adolescents and their caregivers.

OBJECTIVE: To explore influences on adolescent diet and physical activity, from the perspectives of adolescents and their caregivers, in Jimma, Ethiopia. DESIGN: Qualitative design, using focus group discussions (FGD). SETTING: A low-income setting in Jimma, Ethiopia. PARTICIPANTS: Five FGD with adolescents aged 10-12 years and 15-17 years (n 41) and three FGD with parents (n 22) were conducted. RESULTS: Adolescents displayed a holistic understanding of health comprising physical, social and psychological well-being. Social and cultural factors were perceived to be the main drivers of adolescent diet and physical activity. All participants indicated that caregivers dictated adolescents' diet, as families shared food from the same plate. Meals were primarily determined by caregivers, whose choices were driven by food affordability and accessibility. Older adolescents, particularly boys, had opportunities to make independent food choices outside of the home which were driven by taste and appearance, rather than nutritional value. Many felt that adolescent physical activity was heavily influenced by gender. Girls' activities included domestic work and family responsibilities, whereas boys had more free time to participate in outdoor games. Girls' safety was reported to be a concern to caregivers, who were fearful of permitting their daughters to share overcrowded outdoor spaces with strangers. CONCLUSIONS: Adolescents and caregivers spoke a range of social, economic and cultural influences on adolescent diet and physical activity. Adolescents, parents and the wider community need to be involved in the development and delivery of effective interventions that will take into consideration these social, economic and cultural factors.

Liquid-based cytology for the detection of cervical intraepithelial lesions in Jimma town, Ethiopia.

BACKGROUND: Cervical cancer is the second leading type of female cancer in Ethiopia. Screening for cervical cancer is primarily conducted using visual inspection with 5% acetic acid (VIA). Liquid-based cytology (LBC) is not yet widely used in Ethiopia. METHOD: Women aged 21-65 years were tested using LBC and VIA to detect cervical dysplasia. Logistic regression analysis was conducted to identify associated factors. Cohen's Kappa test was conducted to test agreement between LBC and VIA. RESULTS: Forty-two percent (n = 188) of 448 participants were 31 to 40 years of age and only two participants were above 60. Of the 448 participants, 419 (93.5%) were tested with LBC, 294 (65.6%) VIA and 272 (60.7%) with both LBC and VIA. Among women screened using LBC, 305 (72.8%) were negative for intraepithelial lesion or malignancy (NILM), 97 (23.2%) had low-grade squamous intraepithelial lesion (LSIL) and 17 (4.1%) had high-grade squamous intraepithelial lesion (HSIL). Presence of cervical lesions was generally lower in younger and older women. Majority, 39 (40%) of women with LSIL and 10 (59%) with HSIL were 41-50 years of age. Women aged 51-60 were more likely to have abnormal intraepithelial lesions compared to women aged 21-30 (AOR = 20.9, 95% CI = [7.2-60.9], p = 0.00). Out of 47 (10.8%) HIV-positive women, 14 (32.56%) had intraepithelial lesions of which 10 (23.3%) and 4 (9.3%) had LSIL and HSIL, respectively. Among women screened with VIA, 18 (6.1%) were positive; among the 272 (60.7%) women screened using both LBC and VIA, 6 (2.2%) were positive on both LBC and VIA tests. The level of agreement between the two tests was weak at a statistically significant level (kappa value = 0.155, p = 0.006). CONCLUSION: LBC demonstrated high rates of cervical squamous intra-epithelial lesions in our study. VIA was a less reliable predictor of cervical squamous intra-epithelial lesions than LBC. Evaluating diagnostic accuracy of both LBC and VIA against a histological endpoint should be completed before adopting either or both screening modalities.

Critical evaluation of the appetite test for children with severe acute malnutrition.

OBJECTIVES: The appetite test is used to risk stratify for children with severe acute malnutrition (SAM) in inpatient or outpatient care. The test is recommended in guidelines despite lack of evidence. We evaluated its ability to identify children at risk of a poor treatment outcome. METHODS: We conducted an observational study of children diagnosed with SAM at three health facilities in Ethiopia. The appetite test was done independently, and the result did not affect decisions about hospitalisation and clinical care. Data were analysed using mixed linear and logistic regression models. RESULTS: Appetite was tested in 298 (89%) of 334 children enrolled; 56 (19%) passed. Children failing the appetite test had a 6.6% higher weight gain per day (95% CI: 2.6, 10.8) adjusted for type of treatment, oedema, duration of follow-up and age than children passing the test. We found medical complications in 179 (54%) children. Medical complications were associated with blood markers of metabolic disturbance. Children with medical complications tended to have lower weight gain than those without complications (3.5%, 95% CI: -0.25, 7.0). Neither the appetite test nor medical complications were correlated with bacteraemia or treatment failure. CONCLUSIONS: Our findings question the use of the appetite test to identify children who need inpatient care. An assessment of medical complications alone could be a useful risk indicator but needs to be evaluated in other settings.

OBJECTIF: Le test de l'appétit est utilisé pour stratifier les risques chez les enfants souffrant de malnutrition aiguë sévère (MAS) en soins hospitaliers ou ambulatoires. Le test est recommandé dans les directives malgré le manque d'évidence. Nous avons évalué sa capacité à identifier les enfants à risque de mauvais résultats de traitement. MÉTHODES: Nous avons mené une étude observationnelle chez des enfants diagnostiqués avec une MAS dans trois établissements de santé en Ethiopie. Le test de l'appétit a été effectué indépendamment et le résultat n'a pas affecté les décisions d'hospitalisation et de soins cliniques. Les données ont été analysées à l'aide de modèles de régression linéaire et logistique mixtes. RÉSULTATS: : L'appétit a été testé chez 298 (89%) des 334 enfants inscrits; 56 (19%) ont réussi le test. Les enfants qui échouaient au test de l'appétit avaient un gain de poids de 6,6% plus élevé par jour (IC95%: 2,6 à 10,8) ajusté pour le type de traitement, l'œdème, la durée du suivi et l'âge que les enfants réussissant le test. Nous avons trouvé des complications médicales chez 179 (54%) enfants. Des complications médicales ont été associées à des marqueurs sanguins de troubles métaboliques. Les enfants souffrant de complications médicales avaient tendance à avoir un gain de poids plus faible que ceux sans complications (3,5% ; IC95%: -0,25 à 7,0). Ni le test de l'appétit ni les complications médicales ne corrélaient avec une bactériémie ou à un échec du traitement CONCLUSION: Nos résultats remettent en question l'utilisation du test de l'appétit pour identifier les enfants qui ont besoin de soins hospitaliers. Une évaluation des complications médicales à elle seule pourrait être un indicateur de risque utile, mais doit être évaluée dans d'autres contextes MOTS-CLÉS: malnutrition aiguë sévère, appétit, gestionnaire de communauté, évaluation des risques, aliments thérapeutiques.

Therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Chewaka District, Ethiopia.

BACKGROUND: The efficacy of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria in south-western Ethiopia is poorly documented. Regular monitoring of drug efficacy is an important tool for supporting national treatment policies and practice. This study investigated the therapeutic efficacy of AL for the treatment of P. falciparum malaria in Ethiopia. METHODS: The study was a one-arm, prospective, evaluation of the clinical and parasitological, responses to directly observed treatment with AL among participants 6 months and older with uncomplicated P. falciparum malaria. Real-time polymerase chain reaction (PCR) and nested PCR reaction methods were used to quantify and genotype P. falciparum. A modified protocol based on the World Health Organization 2009 recommendations for the surveillance of anti-malarial drug efficacy was used for the study with primary outcomes, clinical and parasitological cure rates at day-28. Secondary outcomes assessed included patterns of fever and parasite clearance. Cure rate on day-28 was assessed by intention to treat (ITT) and per protocol (PP) analysis. Parasite genotyping was also performed at baseline and at the time of recurrence of parasitaemia to differentiate between recrudescence and new infection. RESULTS: Of the 80 study participants enrolled, 75 completed the follow-up at day-28 with ACPR. For per protocol (PP) analysis, PCR-uncorrected and-corrected cure rate of AL among the study participants was 94.7% (95% CI 87.1-98.5) and 96% (95% CI 88.8-99.2), respectively. For intention to treat (ITT) analysis, the cure rate was 90% (95% CI 88.8-99.2). Based on Kaplan-Meier survival estimate, the cumulative incidence of failure rate of AL was 3.8% (95% CI 1.3-11.4). Only three participants 3.8% (95% CI 0.8-10.6) of the 80 enrolled participants were found to be positive on day-3. The day three-positive participants were followed up to day 28 and did not correspond to treatment failures observed during follow-up. Only 7.5% (6/80) of the participants were gametocyte-positive on enrollment and gametocytaemia was absent on day-2 following treatment with AL. CONCLUSIONS: The therapeutic efficacy of AL is considerably high (above 90%). AL remained highly efficacious in the treatment of uncomplicated malaria in the study area resulted in rapid fever and parasite clearance as well as low gametocyte carriage rates despite the use of this combination for more than 15 years.

Genetic diversity and genotype multiplicity of Plasmodium falciparum infection in patients with uncomplicated malaria in Chewaka district, Ethiopia.

BACKGROUND: Genetic diversity in Plasmodium falciparum poses a major threat to malaria control and elimination interventions. Characterization of the genetic diversity of P. falciparum strains can be used to assess intensity of parasite transmission and identify potential deficiencies in malaria control programmes, which provides vital information to evaluating malaria elimination efforts. This study investigated the P. falciparum genetic diversity and genotype multiplicity of infection in parasite isolates from cases with uncomplicated P. falciparum malaria in Southwest Ethiopia. METHODS: A total of 80 P. falciparum microscopy and qPCR positive blood samples were collected from study participants aged 6 months to 60 years, who visited the health facilities during study evaluating the efficacy of artemether-lumefantrine from September-December, 2017. Polymorphic regions of the msp-1 and msp-2 were genotyped by nested polymerase chain reactions (nPCR) followed by gel electrophoresis for fragment analysis. RESULTS: Of 80 qPCR-positive samples analysed for polymorphisms on msp-1 and msp-2 genes, the efficiency of msp-1 and msp-2 gene amplification reactions with family-specific primers were 95% and 98.8%, respectively. Allelic variation of 90% (72/80) for msp-1 and 86.2% (69/80) for msp-2 were observed. K1 was the predominant msp-1 allelic family detected in 20.8% (15/72) of the samples followed by MAD20 and RO33. Within msp-2, allelic family FC27 showed a higher frequency (26.1%) compared to IC/3D7 (15.9%). Ten different alleles were observed in msp-1 with 6 alleles for K1, 3 alleles for MAD20 and 1 allele for RO33. In msp-2, 19 individual alleles were detected with 10 alleles for FC27 and 9 alleles for 3D7. Eighty percent (80%) of isolates had multiple genotypes and the overall mean multiplicity of infection was 3.2 (95% CI 2.87-3.46). The heterozygosity indices were 0.43 and 0.85 for msp-1 and msp-2, respectively. There was no significant association between multiplicity of infection and age or parasite density. CONCLUSIONS: The study revealed high levels of genetic diversity and mixed-strain infections of P. falciparum populations in Chewaka district, Ethiopia, suggesting that both endemicity level and malaria transmission remain high and that strengthened control efforts are needed in Ethiopia.

Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir.

BACKGROUND: Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF. METHODS: HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. RESULT: Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (- 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. CONCLUSION: Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.

HIV and metabolic syndrome in an Ethiopian population.

BACKGROUND: The global prevalence of metabolic syndrome (MS) is increasing due to lifestyle changes. Studies have found that MS is associated with human immunodeficiency virus (HIV) and antiretroviral treatment (ART), but controversies still exist on associations between HIV and MS. AIMS: To assess associations between HIV and MS among ART-naïve HIV positive individuals compared to HIV negative individuals. SUBJECTS AND METHODS: A cross-sectional study among ART-naïve HIV positive and HIV negative individuals recruited from HIV treatment and testing facilities in Ethiopia. Information was collected on components of MS: waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL-C), blood pressure and fasting plasma glucose (FPG). Data were analysed using logistic and linear regression stratified by sex and adjusted for age, wealth and education. RESULTS: Data from 329 HIV positive and 100 HIV negative individuals were included. HIV positive status was associated with higher odds of MS in women (OR: 3.56, 95%CI: 1.25; 10.15) (n = 292), but not in men (OR: 0.98, 95%CI: 0.22; 4.30) (n = 137), interaction: p= .11. Associations between HIV and components of MS were strongest for HDL-C among women and for FPG among men. The most prevalent components of MS in HIV positive individuals were elevated triglycerides, reduced HDL-C and elevated FPG. CONCLUSIONS: HIV was associated with MS among ART-naïve women, suggesting that MS should be evaluated before initiating ART and monitored during treatment to identify those at risk of developing diabetes and cardiovascular disease (CVD).

Associations of fat mass and fat-free mass accretion in infancy with body composition and cardiometabolic risk markers at 5 years: The Ethiopian iABC birth cohort study.

BACKGROUND: Accelerated growth in early childhood is an established risk factor for later obesity and cardiometabolic disease, but the relative importance of fat mass (FM) and fat-free mass (FFM) accretion is not well understood. We aimed to study how FM and FFM at birth and their accretion during infancy were associated with body composition and cardiometabolic risk markers at 5 years. METHODS AND FINDINGS: Healthy children born at term were enrolled in the Infant Anthropometry and Body Composition (iABC) birth cohort between December 2008 and October 2012 at Jimma University Specialized Hospital in the city of Jimma, Ethiopia. FM and FFM were assessed using air displacement plethysmography a median of 6 times between birth and 6 months of age. In 507 children, we estimated individual FM and FFM at birth and their accretion over 0-3 and 3-6 months of age using linear-spline mixed-effects modelling. We analysed associations of FM and FFM at birth and their accretion in infancy with height, waist circumference, FM, FFM, and cardiometabolic risk markers at 5 years using multiple linear regression analysis. A total of 340 children were studied at the 5-year follow-up (mean age: 60.0 months; girls: 50.3%; mean wealth index: 45.5 out of 100; breastfeeding status at 4.5 to 6 months post-partum: 12.5% exclusive, 21.4% almost exclusive, 60.6% predominant, 5.5% partial/none). Higher FM accretion in infancy was associated with higher FM and waist circumference at 5 years. For instance, 100-g/month higher FM accretion in the periods 0-3 and 3-6 months was associated with 339 g (95% CI: 243-435 g, p < 0.001) and 367 g (95% CI: 250-484 g, p < 0.001) greater FM at 5 years, respectively. Higher FM at birth and FM accretion from 0 to 3 months were associated with higher FFM and cholesterol concentrations at 5 years. Associations for cholesterol were strongest for low-density lipoprotein (LDL)-cholesterol, and remained significant after adjusting for current FM. A 100-g higher FM at birth and 100-g/month higher FM accretion from 0 to 3 months were associated with 0.16 mmol/l (95% CI: 0.05-0.26 mmol/l, p = 0.005) and 0.06 mmol/l (95% CI: 0.01-0.12 mmol/l, p = 0.016) higher LDL-cholesterol at 5 years, respectively. Higher FFM at birth and FFM accretion in infancy were associated with higher FM, FFM, waist circumference, and height at 5 years. For instance, 100-g/month higher FFM accretion in the periods 0-3 and 3-6 months was associated with 1,002 g (95% CI: 815-1,189 g, p < 0.001) and 624 g (95% CI: 419-829 g, p < 0.001) greater FFM at 5 years, respectively. We found no associations of FM and FFM growth with any of the other studied cardiometabolic markers including glucose, HbA1c, insulin, C-peptide, HOMA-IR, triglycerides, and blood pressure. Non-attendance at the 5-year follow-up visit was the main limitation of this study, which may have introduced selection bias and limited the power of the regression analyses. CONCLUSIONS: FM accretion in early life was positively associated with markers of adiposity and lipid metabolism, but not with blood pressure and cardiometabolic markers related to glucose homeostasis. FFM accretion was primarily related to linear growth and FFM at 5 years.

Higher Weight and Weight Gain after 4 Years of Age Rather than Weight at Birth Are Associated with Adiposity, Markers of Glucose Metabolism, and Blood Pressure in 5-Year-Old Ethiopian Children.

BACKGROUND: Fetal and early life growth is associated with adult risk of obesity and cardiometabolic disease. However, little is known about the relative importance of birth weight and successive periods of weight gain on markers of cardiometabolic risk in childhood in low-income populations. OBJECTIVES: The objective was to study associations of birth weight and weight gain velocities in selected age intervals from birth to 60 mo with height, fat-free mass (FFM), and markers of adiposity and cardiometabolic risk at 60 mo. METHODS: In a prospective cohort study of 375 Ethiopian children aged 60 mo, we estimated individual weight gain velocities in the periods between birth and 3, 6, 24, 48, and 60 mo using linear-spline mixed-effects modeling. Subsequently, we analyzed associations of birth weight, weight gain velocities, and current weight with height, FFM, and markers of adiposity and cardiometabolic risk. RESULTS: Weight gain from 48 to 60 mo and weight at 60 mo rather than birth weight were the strongest correlates of insulin, C-peptide, HOMA-IR, blood pressure, height, FFM, waist circumference, and fat mass at 60 mo. For instance, 1 SD higher (1 SD = 50 g/mo) weight accretion from 48 to 60 mo was associated with a higher insulin of 23.3% (95% CI: 9.6%, 38.8%), C-peptide of 11.4% (2.7%, 20.8%), systolic blood pressure of 1.4 mm Hg (0.6, 2.3 mm Hg), fat mass of 0.72 kg (0.59, 0.85 kg), and FFM of 0.70 kg (0.56, 0.85 kg). Weight gain from 0 to 3 mo was positively associated with LDL cholesterol, systolic blood pressure, height, and the body composition indices, and weight gain from 24 to 48 mo was inversely associated with blood glucose. CONCLUSIONS: In 60-mo-old Ethiopian urban children, weight gain and weight after 48 mo rather than weight at birth may represent a sensitive period for variations in markers of adiposity and glucose metabolism. The birth cohort is registered at https://www.isrctn.com/ as ISRCTN46718296.

Prolonged and persistent diarrhoea is not restricted to children with acute malnutrition: an observational study in Ethiopia.

OBJECTIVES: To assess the prevalence of prolonged and persistent diarrhoea, to estimate their co-occurrence with acute malnutrition and association with demographic and clinical factors. METHODS: Case-control study where cases were children under 5 years of age with diarrhoea and controls were children without diarrhoea, frequency-matched weekly by age and district of residency. Controls for cases 0-11 months were recruited from vaccination rooms, and controls for cases 12-59 months were recruited by house visits using random locations in the catchment area of the study sites. Data were analysed by mixed model logistic regression. RESULTS: We enrolled 1134 cases and 946 controls. Among the cases, 967 (85%) had acute diarrhoea (AD), 129 (11%) had ProD and 36 (3.2%) had PD. More cases had acute malnutrition at enrolment (17% vs. 4%, P < 0.0001) and more were born prematurely (5.7% vs. 1.8%, P < 0.0001) than controls. About 75% of ProPD cases did not have acute malnutrition. Cases with AD and ProPD had different symptomatology, even beyond illness duration. CONCLUSIONS: ProPD is common among children presenting with diarrhoea and is not confined to children with acute malnutrition. There is an urgent need for studies assessing causes of ProPD with and without acute malnutrition to develop treatment guidelines for these conditions.

OBJECTIFS: Evaluer la prévalence des diarrhées prolongées et persistantes, estimer leur co-occurrence avec la malnutrition aiguë et leur association avec des facteurs démographiques et cliniques. MÉTHODES: Etude cas-témoins portant sur des enfants de moins de 5 ans souffrant de diarrhée et sur des témoins, des enfants sans diarrhée, appariées toutes les semaines, en fonction de l'âge et du district de résidence. Les témoins pour les cas de 0 à 11 mois ont été recrutés dans les salles de vaccination et les témoins pour les cas de 12 à 59 mois ont été recrutés au cours de visites à domicile en utilisant des endroits aléatoires dans la zone de recrutement des sites d'étude. Les données ont été analysées par la régression logistique de modèle mixte. RÉSULTATS: Nous avons inscrit 1134 cas et 946 témoins. Parmi les cas, 967 (85%) avaient une diarrhée aiguë (DA), 129 (11%) étaient atteints de diarrhées prolongée (ProD) et 36 (3,2%) de diarrhées persistante (DP). La malnutrition aiguë au moment de l'inscription était plus fréquente (17% contre 4%, P < 0,0001) et davantage étaient nés prématurément (5,7% contre 1,8%, P < 0,0001) par rapport aux témoins. 75% des cas de ProPD ne souffraient pas de malnutrition aiguë. Les cas de DA et de ProPD avaient une symptomatologie différente, même au-delà de la durée de la maladie. CONCLUSIONS: La ProPD est fréquente chez les enfants présentant une diarrhée et ne se limitait pas aux enfants souffrant de malnutrition aiguë. Il est urgent que des études évaluant les causes de ProPD avec et sans malnutrition aiguë développent des recommandations de traitement pour ces affections.