Laboratory capacity expansion: lessons from establishing molecular testing in regional referral laboratories in Ethiopia.

Respiratory viruses contribute to high morbidity and mortality in Africa. In 2020, the Ohio State University's Global One Health Initiative, in collaboration with the Ethiopian Public Health Institute and the US Centers for Disease Control and Prevention, took action to strengthen Ethiopia's existing respiratory virus surveillance system through decentralization of laboratory testing and scale-up of national and regional capacity for detecting respiratory viruses. In August 2022, four regional laboratories were established, thereby raising the number of reference laboratories conducting respiratory virus surveillance to five. This article highlights lessons learned during implementation and outlines processes undertaken for laboratory scale-up and decentralization.

Applicability of selected Brighton Collaboration case definitions in low-resource settings: A prospective hospital-based active surveillance in Addis Ababa, Ethiopia.

INTRODUCTION: Standardizing case definitions for priority vaccine safety conditions facilitates uniform evaluation and consolidation of data obtained from different settings. The Brighton Collaboration case definitions (BCCD) were created to support this harmonization and enable classification from level 1 (most certain) to level 5 (not a case) of certainty. Assessing the performance of BCCD in practice is critical, particularly in resource-limited settings, where many new vaccines may be introduced without prior monitoring in high-income countries. We assessed the performance of BCCD in Addis Ababa, Ethiopia, as applicable to COVID-19 and other vaccines. METHODS: Active surveillance was conducted at Tikur Anbessa Specialized Hospital, the largest referral hospital in Ethiopia. During June 1, 2022-May 31, 2023, three trained physicians prospectively identified patients eligible for COVID-19 vaccination (regardless of vaccine receipt) who presented with one or more of eleven pre-specified adverse events of special interest (AESI) from the emergency department and inpatient wards. Standardized data collection forms were used to capture patient information and assign level of certainty (LOC), regardless of vaccination status for COVID-19. We conducted descriptive analysis to characterize cases and the LOCs reached for each AESI. RESULTS: We detected 203 AESI cases. The most detected conditions were thrombosis and thromboembolism (n = 100, 49 %) and generalized convulsions (n = 38, 19 %). Ninety-six percent of the cases were confirmed at levels 1-3 (n = 187) or level 5 (n = 9) LOC. Non-classifiable (level 4) cases were observed for pericarditis (n = 2), encephalitis (n = 2), myelitis (n = 2), and generalized convulsion (n = 1). CONCLUSION: The BCCD were successfully applied in > 95 % of cases in a large referral hospital in Ethiopia, with generalized convulsion, pericarditis, and encephalomyelitis as the exceptions. We recommend further evaluation in other low-resource settings, particularly in rural or non-referral hospitals, to gain additional insights into performance of these definitions for revision or adaptation, as needed.

Antimicrobial resistance trends in clinical Escherichia coli and Klebsiella pneumoniae in Ethiopia.

Background: Clinicians rely on local antimicrobial resistance pattern data to guide empiric treatment for seriously ill patients when culture and antimicrobial susceptibility testing results are not immediately available. Objective: This study aimed to analyse 5-year trends in antimicrobial resistance profiles of Escherichia coli and Klebsiella pneumoniae isolates. Methods: Bacteriology reports from 2017 to 2021 at the Ethiopian Public Health Institute were analysed retrospectively. Isolates were identified using either the VITEK 2 Compact system, the BD Phoenix M50 instrument, or conventional biochemical tests. Antimicrobial susceptibility testing was conducted using either the Kirby-Bauer disk diffusion method or the VITEK 2 Compact system and BD Phoenix M50 systems available at the time of testing. The Cochran Armitage trend test was employed to test the significance of antimicrobial resistance trends over time. P-values less than 0.05 were considered statistically significant. Results: Of the 5382 bacteriology reports examined, 458 (9%) were on E. coli and 266 (5%) were on K. pneumoniae. Both K. pneumoniae (88%) and E. coli (65%) demonstrated high resistance to extended-spectrum cephalosporins. However, both K. pneumoniae (14%) and E. coli (5%) showed lower rates of resistance to carbapenems compared to other antimicrobials. In K. pneumoniae, resistance to carbapenems (from 0% to 38%; p < 0.001) and ciprofloxacin (from 41% to 90%; p < 0.001) increased significantly between 2017 and 2021. Conclusion: Both organisms showed very high resistance to broad-spectrum antibiotics. Additionally, K. pneumoniae demonstrated a statistically significant rise in ciprofloxacin and carbapenem resistance. What this study adds: This study emphasises the significance of regular reporting of local antimicrobial resistance patterns as this information can guide appropriate empiric therapy and efforts to address antimicrobial resistance issues.

Predictors of length of hospital stay for preterm infants in Ethiopia: a competing risk analysis.

Background: Length of hospital stay (LOS) is one of the essential indicators for evaluating the efficiency and the quality-of-care service delivered. predicting LOS is critical for resource allocation, decision-making, lowering neonatal morbidity and death, enhancing clinical outcomes and parent counseling. In addition, extended hospital stays (long LOS_NICU) place a burden on the healthcare systems decreasing bed turnover rates as well as their financial stand and the mental stress on families. In Ethiopia, there is limited evidence on the determinant factors that influence on LOS. Objectives: To determine factors affecting neonatal intensive care unit length of stay for all preterm newborns who were discharged alive. Method: The study used a secondary data source, was collected for the Study of Illness in Preterm (SIP) infants project. The research study was a multicenter, cross-sectional, observational clinical study that took place in five Ethiopia hospitals from July 1, 2016, to May 31, 2018. The predictors of LOS were determined using Fine-Gray's competing risk analysis. Results: For this study 3,511 preterm infants admitted to the NICU were analyzed. About 28.8% of the preterm infants died during their time in neonatal care while 66.6% were discharged alive. At the end of the study 4.6% babies were still in the NICU. The overall median LOS (death or discharge) was 7 days, with an interquartile range of 8 days. The cumulative incidence of discharge rose with increasing in gestational age and birth weight, on the contrary, the rate of discharge was decreased by 45.7% with the development of RDS (SDH ratio: 0.543), by 75.9% with the development of apnea (SDH ratio: 0.241), by 36.2% with sepsis, and by 43.6% with pneumonia (SDH ratio: 0.564). Conclusions: Preterm newborns with a low gestational age and birth weight have a greater probability of having a prolonged LOS. Complications of the medical conditions RDS, apnea, sepsis, pneumonia, anemia, asphyxia, and NEC substantially raise LOS considerably.

Fecal Carriage of Carbapenem Resistant Enterobacterales and Associated Factors Among Admitted Patients in Saint Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

Purpose: The Enterobacterales family colonizes the human gut as normal flora in all age groups, with bacterial infections being the most common cause. Resistance is currently observed in all normal flora. The aim of this study was to determine the frequency of fecal carriage of carbapenem-resistant Enterobacterales (CRE), carbapenemase-producing Enterobacterales (CPE), and associated factors in the faeces of admitted patients. Methods: A cross-sectional study was conducted in Saint Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. A total of 384 rectal swabs were collected from various wards in admitted patients who have consented to participate. The specimens were inoculated on a MacConkey agar plate, and then they were incubated at 37 °C for 18 to 24 hours. Using the BD PhoenixTM M50 compact system identification and antimicrobial susceptibility testing were performed. Using the modified carbapenem inactivation method, it was determined whether the carbapenem-resistant bacterial isolate produced carbapenemase or not. Results: Overall prevalence of carbapenem-resistant Enterobacterales carriage and carbapenemase producing Enterobacterales in admitted patients was 17.2% (95%, Confidence Interval: 13.3-21.1%) and 7% (95%, Confidence Interval: 4.7-9.9%), respectively. The predominate carbapenem-resistant Enterobacterales in fecal carriage was K. pneumoniae, 15.4% (23/149), E. cloacae 15.4% (6/39), followed by E. coli 12.4% (37/307) of carbapenem-resistant Enterobacterales (CRE) isolate. Carbapenem-resistant Enterobacterales carriage isolates showed large level of resistance to ciprofloxacin, and sulfamethoxazole-trimethoprim. Prior intake of antibiotics (Odds Ratio 2.42, 95% CI: 11.186-4.95) was significantly associated with higher carbapenem-resistant Enterobacterales carriage. Conclusion: We observed a high prevalence of carbapenem-resistant Enterobacterales carriage and carbapenemase-producing Enterobacterales among admitted patients. There were only amikacin and colistin that could be effective for carbapenem-resistant Enterobacterales isolates. Hence, the control of carbapenem-resistant Enterobacterales carriage should be given priority by carbapenem-resistant Enterobacterales screening for fecal of admitted patients, and adhering to good infection prevention practice in hospital settings.

The effect of a health extension program on improving water, sanitation, and hygiene practices in rural Ethiopia.

BACKGROUND: To make basic primary health care services accessible, especially to the rural community, the government of Ethiopia launched the Health Extension Program (HEP) in 2004. Most of components of HEP are dedicated to hygiene and sanitation. Few studies have assessed the role of the Health Extension Program in improving water, hygiene, and sanitation (WASH) practices in Ethiopia. This study explored the role of health extension workers (HEWs) in influencing household water treatment practices, latrine ownership, latrine use and ownership, and the use of hand-washing facilities on the incidence of diarrheal diseases among the children under five years of age in rural Ethiopia. METHODS: Using a cross sectional design, we conducted a national assessment that covered all nine regions of Ethiopia. We conducted face-to-face interviews among a sample of 6430 rural households using a structured questionnaire and an observation checklist to collect data from March 2018 to May 2019. Multilevel logistic regressions models were used to determine the relationships between the exposure of households to HEWs and WASH practice outcomes such as the use of water from an improved water source, household water treatment practices, availability of hand-washing and hand-washing with soap and water, availability of latrines, and use of latrines as well as the incidence of diarrheal diseases among children age 5 and younger. Our models were adjusted for covariates and confounders and P-values less than 5% were set to determine statistical significance. RESULTS: We found that 72.7% of rural households had some type of latrine and 27.3% reported practicing open defecation. A total of 71.5% of rural households had access to drinking water from improved water sources, but only 9.4% reported practicing household water treatment. Exposure to HEWs was positively associated with household water treatment practices (AOR: 1.46; 95% CI = 1.01-2.10) and latrine availability (AOR: 1.44; 95% CI = 1.15-1.80). Among the households who were either visited by HEWs at their home or the that visited health posts to meet with the HEWs, being exposed to WASH health education by HEWs was significantly associated with the availability of a hand-washing facility (AOR: 5.14; 95% CI = 4.11-6.42) and latrine availability (AOR: 1.48; 95% CI = 1.10-2.01). However, we did not find a relationship between the incidence of diarrhea among children age 5 and under and exposure to HEWs (AOR: 2.09; 95% CI = 0.73- 6.62). CONCLUSION: Our results show a significant association between exposure to the Health Extension Program/ HEWs and improved household water treatment practices, latrine construction, and the availability of hand-washing facilities in rural Ethiopia, suggesting the need to strengthen efforts to change WASH behavior through the Heath Extension Program. On the other hand, further investigation is needed regarding the spillover effect of latrine use practices and the reduction of the incidence of diarrheal diseases.

Bacterial and fungal profile, drug resistance pattern and associated factors of isolates recovered from blood samples of patients referred to Ethiopian Public Health Institute: cross-sectional study.

BACKGROUND: Blood stream infections are serious infections that usually induce prolongation of hospital stay, morbidity and mortality in several countries including Ethiopia. The aim of this study was to determine bacterial and fungal profile, their drug resistance patterns, and risk factors associated with blood stream infections. METHODS: A cross sectional study design was conducted from February 23 to June 23, 2020 at Ethiopian public health. A structured questionnaire was used to collect data on socio-demographic factors and clinical conditions. Blood specimens were analyzed using standard microbiological techniques. Antimicrobial susceptibility tests were performed using Kirby-Bauer disc diffusion technique and Vitek compact 2. Simple and multiple logistic regressions were used to assess the potential risk factors. RESULTS: A total of 175 pathogens isolated from 346 blood specimens. Of these, 60% Gram-negative bacteria, 30.86% Gram-positive bacteria and 9.14% fungal isolates were identified. Burkholderia cepacia and Coagulase negative staphylococcus were the predominant pathogen among Gram-negative and Gram-positive bacteria respectively. Among fungus, Candida krusei (56.25%) was the most predominant isolate. The highest proportions of antibacterial resistance were observed among 3rd generation cephalosporin and penicillin. Most fungal isolates expressed resistance to fluconazole. Sex (P = 0.007), age (P < 0.001) and use of invasive medical devices (P = 0.003) were identified as risk factors for bacterial blood stream infections. CONCLUSION: The study showed high prevalence of blood stream infection was due to B. cepacia and non-C. albicans spp. This finding alarming ongoing investigation of blood stream infection is important for recognizing future potential preventive strategies including environmental hygiene and management of comorbid medical diseases to reduce the problem.

Disparity in Birth Size of Ethiopian Preterm Infants in Comparison to International INTERGROWTH-21st Data.

Background. Patterns of fetal growth are largely influenced by environmental, nutritional, and socioeconomic factors more than differences in populations. The aim of this study was to assess anthropometric measurements of Ethiopian preterm infants at birth and compare the results with the international INTERGROWTH-21st data. Patients and methods. We analyzed anthropometric data on live-born singleton preterm infants enrolled in a hospital-based multicenter study of illness in preterm infants (SIP). Eligible newborns with gestational age of 28-36 weeks were included. Gestational age (GA) and sex-specific mean and standard deviations (SD), 10th, 50th, 90th, centile values for birth weight, length and head circumference (HC) were calculated and compared with INTERGROWTH-21st data. Result. A total of 2763 preterm infants were included in the study, 54% were male. The prevalence of small for GA (SGA) (<10th percentile) and large for GA (LGA) (>90th percentile) were 10.8% and 9.9%, respectively. In all 3 parameters, the mean values of boys were higher than of girls. Birth weight centiles were comparable to international averages at lower GA, then after GA of 32 weeks the 10th, 50th, and 90th centile values were 100-500 g less than the international averages. The head circumference centiles were mostly comparable, and the 90th centile values were greater than the international averages across the GA and in both sexes. Conclusion. The infants' birth weights were smaller at higher GA, which may indicate maternal undernutrition in the third trimester of pregnancy. Strengthening antenatal nutrition counseling and providing nutrition supplementation might improve the birth weight.

Hypothermia in Preterm Newborns: Impact on Survival.

Background. Globally, prematurity is the leading cause of neonatal mortality, and hypothermia is one of its contributing factors. The goal of this study was to determine the association between hypothermia and mortality. Methods. A prospective, multi-center, descriptive clinical study was conducted in 5 hospitals in Ethiopia. Axillary temperatures were taken at the time of admission to the newborn intensive care units (NICU) and followed during the NICU stay. Results. A total of 3852 premature neonates (<37 weeks) were admitted to the NICUs from July 2016 to May 2018. Of these infants, 1109 (28.8%) died and 2991 (79.6%) had hypothermia. Hypothermia was associated with perinatal asphyxia (89.5%), RDS (86.2%), and resuscitation at birth (82.7%). Admission temperatures in preterm newborns were inversely associated with mortality and morbidity. Conclusion. Hypothermia at admission is associated with neonatal mortality in premature neonates in Ethiopia. RDS and perinatal asphyxia were the main factors associated with hypothermia. The very high prevalence and association with mortality warrants quality improvement interventions.

Preterm Nutrition and Clinical Outcomes.

Background. In low-income countries, preterm nutrition is often inadequately addressed. The aim of the study was to assess the patterns of feeding and associated clinical outcomes of preterm neonates admitted to neonatal intensive care units in Ethiopia. Method. This was a multicenter, prospective study. Infants' clinical characteristics at birth, daily monitoring of feeding history, and weight measurements were collected. An outcome assessment was completed at 28 days. Result. For this analysis, 2560 infants (53% male) were eligible. The mean (SD) gestational age was 33.1 (2.2) weeks. During the hospital stay the proportion of infants on breast milk only, preterm formula, term formula, and mixed feeding was 58%, 27.4%, 1.6%, and 34.1%, respectively. Delay in enteral feeding was associated with increased risk of death (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.33-2.78; P < .001) and (OR = 5.06, 95% CI = 3.23-7.87; P < .001) for 1 to 3 and 4 to 6 days of delay in enteral feeding, respectively, after adjusting for possible confounders. The length of delay in enteral feeding was associated with increased risk of hypoglycemia (OR = 1.2, 95% CI = 1.1-1.2; P = .005). The mortality rate was lower in hospitals providing preterm formula more often (P = .04). Half of the infants continued losing weight at the time of discharge. Conclusion. Delayed enteral feeding significantly increases the risk of mortality before discharge and hypoglycemia in preterm infants in resource-limited settings. Ensuring adequate nutritional support of preterm infants is highly needed.

Hyperbilirubinemia in Preterm Infants Admitted to Neonatal Intensive Care Units in Ethiopia.

Background. Hyperbilirubinemia is prevalent and protracted in preterm infants. This study assessed the pattern of hyperbilirubinemia in preterm infants in Ethiopia. Methods. This study was part of multi-centered prospective, cross-sectional, observational study that determined causes of death among preterm infants. Jaundice was first identified based on clinical visual assessment. Venous blood was then sent for total and direct serum bilirubin level measurements. For this study, a total serum bilirubin level ≥5 mg/dL was taken as the cutoff point to diagnose hyperbilirubinemia. Based on the bilirubin level and clinical findings, the final diagnoses of hyperbilirubinemia and associated complications were made by the physician. Result. A total of 4919 preterm infants were enrolled into the overall study, and 3852 were admitted to one of the study's newborn intensive care units. Of these, 1779 (46.2%) infants were diagnosed with hyperbilirubinemia. Ten of these (0.6%) developed acute bilirubin encephalopathy. The prevalence of hyperbilirubinemia was 66.7% among the infants who were less than 28 weeks of gestation who survived. Rh incompatibility (P = .002), ABO incompatibility (P = .0001), and sepsis (P = .0001) were significantly associated with hyperbilirubinemia. Perinatal asphyxia (P-value = 0.0001) was negatively associated with hyperbilirubinemia. Conclusion. The prevalence of hyperbilirubinemia in preterm babies admitted to neonatal care units in Ethiopia was high. The major risk factors associated with hyperbilirubinemia in preterm babies in this study were found to be ABO incompatibility, sepsis, and Rh isoimmunization.

Major causes of death in preterm infants in selected hospitals in Ethiopia (SIP): a prospective, cross-sectional, observational study.

BACKGROUND: Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia. METHODS: We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data. FINDINGS: Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 [45%]); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 [30%]), and asphyxia (151 [14%]). Hypothermia was the most common contributory cause of preterm mortality (770 [69%]). The highest mortality occurred in infants younger than 28 weeks of gestation (89 [86%] of 104), followed by infants aged 28-31 weeks (512 [54%] of 952), 32-34 weeks (349 [18%] of 1975), and 35-36 weeks (159 [8%] of 1888). INTERPRETATION: Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death. FUNDING: Bill & Melinda Gates Foundation.