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 prima-quine 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 GlaxoSmith-Kline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167.)

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.

BackgroundStreptococcus agalactiae (group B Streptococcus, GBS) is the most frequent pathogen isolated from neonates with invasive bacterial disease and responsible for serious infections in newborns such as pneumonia, septicemia and meningitis. Infection is primarily acquired vertically from mothers colonized with GBS. However, the prevalence and antimicrobial susceptibility pattern of GBS among pregnant women in Ethiopia are less studied.MethodsThis cross-sectional study involved 126 pregnant women at 35–37 weeks of gestation attending the antenatal clinic at Jimma University Hospital. Anorectal and vaginal swabs were cultured on to Todd-Hewitt broth medium supplemented with Gentamicin and Nalidixic acid and subsequently sub-cultured on 5 % sheep blood agar followed by identification of isolates based on colonial morphology, Gram stain, catalase reaction, hippurate hydrolysis and Christie, Atkins, Munch-Petersen (CAMP) test, and testing for their susceptibility to antimicrobial agents using the Kirby–Bauer method.ResultsThe overall carriage rate of GBS was 19.0 % (24/126), and the rectal and vaginal carrier rates were 14.3 % (18/126) and 10.4 % (13/126), respectively. Concomitant vaginal and anorectal colonization was recorded in 29.2 % (7/24) of the women who were culture positive. All GBS isolates were susceptible to penicillin G, ampicillin, and vancomycin, but a considerable proportion was resistant to clindamycin (3.2 %), erythromycin (6.5 %), ciprofloxacin (9.7 %), ceftriaxone (9.7 %), norfloxacin (12.9 %), cotrimoxazole (29 %), and tetracycline (45.2 %).ConclusionThis study reveals high carriage rate of GBS among pregnant women compared to some previous studies in Ethiopia. However, further epidemiological investigations should be done in different parts of the country in order to know the actual GBS colonization rate of pregnant women and to consider the possibility of implementing prophylactic treatment to prevent potential adverse maternal and neonatal outcomes. Future studies should be conducted to reveal serotype distributions of GBS in this community.

Background Klebsiella pneumoniae and Escherichia coli are the major extended-spectrum β-lactamase- (ESBL-) producing organisms increasingly isolated as causes of complicated urinary tract infections and remain an important cause of failure of therapy with cephalosporins and have serious infection control consequence. Objective To assess the prevalence and antibiotics resistance patterns of ESBL-producing Escherichia coli and Klebsiella pneumoniae from community-onset urinary tract infections in Jimma University Specialized hospital, Southwest Ethiopia, 2016. Methodology A hospital-based cross-sectional study was conducted, and a total of 342 urine samples were cultured on MacConkey agar for the detection of etiologic agents. Double-disk synergy (DDS) methods were used for detection of ESBL-producing strains. A disc of amoxicillin + clavulanic acid (20/10 µg) was placed in the center of the Mueller–Hinton agar plate, and cefotaxime (30 µg) and ceftazidime (30 µg) were placed at a distance of 20 mm (center to center) from the amoxicillin + clavulanic acid disc. Enhanced inhibition zone of any of the cephalosporin discs on the side facing amoxicillin + clavulanic acid was considered as ESBL producer. Results In the current study, ESBL-producing phenotypes were detected in 23% (n = 17) of urinary isolates, of which Escherichia coli accounts for 76.5% (n = 13) and K. pneumoniae for 23.5% (n = 4). ESBL-producing phenotypes showed high resistance to cefotaxime (100%), ceftriaxone (100%), and ceftazidime (70.6%), while both ESBL-producing and non-ESBL-producing isolates showed low resistance to amikacin (9.5%), and no resistance was seen with imipenem. In the risk factors analysis, previous antibiotic use more than two cycles in the previous year (odds ratio (OR), 6.238; 95% confidence interval (CI), 1.257–30.957; p = 0.025) and recurrent UTI more than two cycles in the last 6 months or more than three cycles in the last year (OR, 7.356; 95% CI, 1.429–37.867; p = 0.017) were found to be significantly associated with the ESBL-producing groups. Conclusion Extended-spectrum β-lactamases- (ESBL-)producing strain was detected in urinary tract isolates. The occurrence of multidrug resistance to the third-generation cephalosporins, aminoglycosides, fluoroquinolones, trimethoprim-sulfamethoxazole, and tetracyclines is more common among ESBL producers. Thus, detecting and reporting of ESBL-producing organisms have paramount importance in the clinical decision-making.

BackgroundMeningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and overuse of antibiotics are potential consequences, especially for viral meningitis.MethodsA prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected.ResultsTwo hundred and eighteen patients were included; 117 (54%) neonates (0–29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm3 and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without.ConclusionsA rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3589-4) contains supplementary material, which is available to authorized users.

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Background Both impaired and accelerated postnatal growth have been associated with adult risks of obesity and cardiometabolic diseases, like type 2 diabetes and cardiovascular disease. However, the timing of the onset of cardiometabolic changes and the specific growth trajectories linking early growth with later disease risks are not well understood. Objectives The aim of this study was to identify distinct trajectories of BMI growth from 0 to 5 y and examine their associations with body composition and markers of cardiometabolic risk at age 5 y. Methods In a prospective birth cohort study of 453 healthy and term Ethiopian children with BMIs assessed a median of 9 times during follow-up, we identified subgroups of distinct BMI trajectories in early childhood using latent class trajectory modeling. Associations of the identified growth trajectories with cardiometabolic markers and body composition at 5 y were analyzed using multiple linear regression analyses in 4 adjustment models for each outcome. Results We identified 4 heterogeneous BMI growth trajectories: stable low BMI (19.2%), normal BMI (48.8%), rapid catch-up to high BMI (17.9%), and slow catch-up to high BMI (14.1%). Compared with the normal BMI trajectory, children in the rapid catch-up to high BMI trajectory had higher triglycerides (TGs) (range of β-coefficients in Models 1–4: 19–21%), C-peptides (23–25%), fat masses (0.48–0.60 kg), and fat-free masses (0.50–0.77 kg) across the 4 adjustment models. Children in the stable low BMI trajectory had lower LDL cholesterol concentrations (0.14–0.17 mmol/L), HDL cholesterol concentrations (0.05–0.09 mmol/L), fat masses (0.60–0.64 kg), and fat-free masses (0.35–0.49 kg), but higher TGs (11–13%). Conclusions The development of obesity and cardiometabolic risks may be established already in early childhood; thus, our data provide a further basis for timely interventions targeted at young children from low-income countries with unfavorable growth patterns. The birth cohort was registered at ISRCTN as ISRCTN46718296.

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