Rotavirus and bacterial diarrhoea among children in Ile-Ife, Nigeria: Burden, risk factors and seasonality.

BACKGROUND: Diarrhoea is a leading cause of death among under-five children globally, with sub-Saharan Africa alone accounting for 1/3 episodes yearly. Viruses, bacteria and parasites may cause diarrhoea. Rotavirus is the most common viral aetiology of diarrhoea in children less than five years globally. In Nigeria, there is scarce data on the prevalence/importance, burden, clinical/risk factors and seasonality of rotavirus and bacteria and this study aims to determine the role of rotavirus and bacteria on diarrhoea cases in children less than five years in Ile-Ife, Nigeria. METHODS: Socio-demographic data, environmental/risk factors and diarrhoiec stool samples were collected from children less than five years presenting with acute diarrhoea. Rotavirus was identified using ELISA. Bacteria pathogens were detected using cultural technique and typed using PCR. Diarrhoeagenic E. coli (DEC) isolates were subjected to antimicrobial susceptibility testing. Pathogen positive and negative samples were compared in terms of gender, age-group, seasonal distribution, and clinical/risk factors using chi-square with two-tailed significance. SPSS version 20.0.1 for Windows was used for statistical analysis. RESULTS: At least one pathogen was detected from 63 (60.6%) children having gastroenteritis while 28 (44.4%) had multiple infections. Rotavirus was the most detected pathogen. Prevalence of rotavirus mono-infection was 22%, multiple infection with bacteria was 45%. Mono-infection prevalence of DEC, Shigella spp., and Salmonella spp. were 5.8% (6/104), 5.8% (6/104), and 2.9% (3/104) and co-infection with RVA were 23.1% (24/104), 21.2% (22/104) and 10.6% (11/104) respectively. All rotaviral infections were observed in the dry season. The pathotypes of DEC detected were STEC and EAEC. Parent earnings and mid-upper arm circumference measurement have statistical correlation with diarrhoea (p = 0.034; 0.035 respectively). CONCLUSION: In this study, rotavirus was more prevalent than bacteria and occurred only in the dry season. Among bacteria aetiologies, DEC was the most common detected. Differences in seasonal peaks of rotavirus and DEC could be employed in diarrhoea management in Nigeria and other tropical countries to ensure optimal limited resources usage in preventing diarrhoea transmission and reducing indiscriminate use of antibiotics.

Impact of the use of surfactant and Nasal CPAP in the reduction of mortality among very low birth weight preterm babies in Ile-Ife, south western Nigeria

Background: Respiratory distress syndrome causes significant morbidity and death especially among very low birth weight babies. Though the use of CPAP and surfactant have been shown to improve survival, these interventions were scarcely available in the past. This study aimed at comparing the clinical outcomes of preterm babies with RDS delivered at the Ife Hospital Unit of the Obafemi Awolowo University Teaching Hospitals Complex at two different periods. Objective: To compare the birth weight specific mortality rates and overall mortality rates of preterm babies with RDS between two periods in the neonatal ward of the Ife Hospital Unit of OAUTHC. Methods: A retrospective study comparing outcomes of 92 babies with RDS at GA 26 to 33+6 weeks between January 2015 and May 2016 and managed with intranasal oxygen alone to 104 babies of same gestational age characteristics between January 2019 and May 2020 who were managed withCPAP/surfactant. Results: The mean weight and gestational age of the babies respectively were 1.36 (±0.37) kg and 31.14 (±2.3) weeks in 2015/2016 and 1.35 (±0.322) kg and 30.95 (±2.24) weeks in 2019/2020. The overall case fatality rate and birth-weight specific mortality rates for ELBW, VLBW and LBW were 33.7%, 62.5%, 35.2% and 9.1% in 2015/2016 and 18.3%, 58.3%, 15.5% and 9.7% respectively in 2019/2020. Conclusion: While the use of CPAP and the administration of surfactant clearly show improved survival among very low birth weight babies who are at increased risk of death from RDS, this was not the case for extreme low birth weight babies.

Costs and cost-effectiveness of management of possible serious bacterial infections in young infants in outpatient settings when referral to a hospital was not possible: Results from randomized trials in Africa.

INTRODUCTION: Serious bacterial neonatal infections are a major cause of global neonatal mortality. While hospitalized treatment is recommended, families cannot access inpatient treatment in low resource settings. Two parallel randomized control trials were conducted at five sites in three countries (Democratic Republic of Congo, Kenya, and Nigeria) to compare the effectiveness of treatment with experimental regimens requiring fewer injections with a reference regimen A (injection gentamicin plus injection procaine penicillin both once daily for 7 days) on the outpatient basis provided to young infants (0-59 days) with signs of possible serious bacterial infection (PSBI) when the referral was not feasible. Costs were estimated to quantify the financial implications of scaleup, and cost-effectiveness of these regimens. METHODS: Direct economic costs (including personnel, drugs and consumable costs) were estimated for identification, prenatal and postnatal visits, assessment, classification, treatment and follow-up. Data on time spent by providers on each activity was collected from 83% of providers. Indirect marginal financial costs were estimated for non-consumables/capital, training, transport, communication, administration and supervision by considering only a share of the total research and health system costs considered important for the program. Total economic costs (direct plus indirect) per young infant treated were estimated based on 39% of young infants enrolled in the trial during 2012 and the number of days each treated during one year. The incremental cost-effectiveness ratio was calculated using treatment failure after one week as the outcome indicator. Experimental regimens were compared to the reference regimen and pairwise comparisons were also made. RESULTS: The average costs of treating a young infant with clinical severe infection (a sub-category of PSBI) in 2012 was lowest with regimen D (injection gentamicin once daily for 2 days plus oral amoxicillin twice daily for 7 days) at US$ 20.9 (95% CI US$ 16.4-25.3) or US$ 32.5 (2018 prices). While all experimental regimens B (injection gentamicin once daily plus oral amoxicillin twice daily, both for 7 days), regimen C (once daily of injection gentamicin injection plus injection procaine penicillin for 2 days, thereafter oral amoxicillin twice daily for 5 days) and regimen D were found to be more cost-effective as compared with the reference regimen A; pairwise comparison showed regimen D was more cost-effective than B or C. For fast breathing, the average cost of treatment with regimen E (oral amoxicillin twice daily for 7 days) at US$ 18.3 (95% CI US$ 13.4-23.3) or US$ 29.0 (2018 prices) was more cost-effective than regimen A. Indirect costs were 32% of the total treatment costs. CONCLUSION: Scaling up of outpatient treatment for PSBI when the referral is not feasible with fewer injections and oral antibiotics is cost-effective for young infants and can lead to increased access to treatment resulting in potential reductions in neonatal mortality. CLINICAL TRIAL REGISTRATION: The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

Simplified antibiotic regimens compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with clinical signs of possible serious bacterial infection when referral is not possible: a randomised, open-label, equivalence trial.

BACKGROUND: WHO recommends hospital-based treatment for young infants aged 0-59 days with clinical signs of possible serious bacterial infection, but most families in resource-poor settings cannot accept referral. We aimed to assess whether use of simplified antibiotic regimens to treat young infants with clinical signs of severe infection was as efficacious as an injectable procaine benzylpenicillin-gentamicin combination for 7 days for situations in which hospital referral was not possible. METHODS: In a multisite open-label equivalence trial in DR Congo, Kenya, and Nigeria, community health workers visited all newborn babies at home, identifying and referring unwell young infants to a study nurse. We stratified young infants with clinical signs of severe infection whose parents did not accept referral to hospital by age (0-6 days and 7-59 days), and randomly assigned each individual within these strata to receive one of the four treatment regimens. Randomisation was stratified by age group of infants. An age-stratified randomisation scheme with block size of eight was computer-generated off-site at WHO. The outcome assessor was masked. We randomly allocated infants to receive injectable procaine benzylpenicillin-gentamicin for 7 days (group A, reference group); injectable gentamicin and oral amoxicillin for 7 days (group B); injectable procaine benzylpenicillin-gentamicin for 2 days, then oral amoxicillin for 5 days (group C); or injectable gentamicin for 2 days and oral amoxicillin for 7 days (group D). Trained health professionals gave daily injections and the first dose of oral amoxicillin. Our primary outcome was treatment failure by day 8 after enrolment, defined as clinical deterioration, development of a serious adverse event (including death), no improvement by day 4, or not cured by day 8. Independent outcome assessors, who did not know the infant's treatment regimen, assessed study outcomes on days 4, 8, 11, and 15. Primary analysis was per protocol. We used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000286044. FINDINGS: In Kenya and Nigeria, we started enrolment on April 4, 2011, and we enrolled the necessary number of young infants aged 7 days or older from Oct 17, 2011, to April 30, 2012. At these sites, we continued to enrol infants younger than 7 days until March 29, 2013. In DR Congo, we started enrolment on Sept 17, 2012, and continued until June 28, 2013. We randomly assigned 3564 young infants to either group A (n=894), group B (n=884), group C (n=896), or group D (n=890). We excluded 200 randomly assigned infants, who did not fulfil the predefined criteria of adherence to treatment and adequate follow-up. In the per-protocol analysis, 828 infants were included in group A, 826 in group B, 862 in group C, and 848 in group D. 67 (8%) infants failed treatment in group A compared with 51 (6%) infants in group B (risk difference -1·9%, 95% CI -4·4 to 0·1), 65 (8%) in group C (-0·6%, -3·1 to 2·0), and 46 (5%) in group D (-2·7%, -5·1 to 0·3). Treatment failure in groups B, C, and D was within the similarity margin compared with group A. During the 15 days after random allocation, 12 (1%) infants died in group A, compared with ten (1%) infants in group B, 20 (2%) infants in group C, and 11 (1%) infants in group D. An infant in group A had a serious adverse event other than death (injection abscess). INTERPRETATION: The three simplified regimens were as effective as injectable procaine benzylpenicillin-gentamicin for 7 days on an outpatient basis in young infants with clinical signs of severe infection, without signs of critical illness, and whose caregivers did not accept referral for hospital admission. FUNDING: Bill & Melinda Gates Foundation grant to WHO.

Oral amoxicillin compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with fast breathing when referral is not possible: a randomised, open-label, equivalence trial.

BACKGROUND: WHO recommends referral to hospital for possible serious bacterial infection in young infants aged 0-59 days. We aimed to assess whether oral amoxicillin treatment for fast breathing, in the absence of other signs, is as efficacious as the combination of injectable procaine benzylpenicillin-gentamicin. METHODS: In a randomised, open-label, equivalence trial at five sites in DR Congo, Kenya, and Nigeria, community health workers followed up all births in the community, identified unwell young infants, and referred them to study nurses. We randomly assigned infants with fast breathing as a single sign of illness or possible serious bacterial infection, whose parents did not accept referral to hospital, to receive either injectable procaine benzylpenicillin-gentamicin once per day or oral amoxicillin treatment twice per day for 7 days. A person who was off-site generated randomisation lists using computer software. Trained health professionals gave injections, but outcome assessors were masked to group allocations. The primary outcome was treatment failure by day 8 after enrolment, defined as clinical deterioration, development of a serious adverse event including death, persistence of fast breathing on day 4, or recurrence up to day 8. The primary analysis was per protocol and we used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000286044. FINDINGS: From April 4, 2011, to March 29, 2013, we enrolled 2333 infants aged 0-59 days with fast breathing as the only sign of possible serious bacterial infection at the five study sites. We assigned 1170 infants to receive injectable procaine benzylpenicillin-gentamicin and 1163 infants to receive oral amoxicillin. In the per-protocol analysis, from which 137 infants were excluded, we included 1061 (91%) infants who fulfilled predefined criteria of adherence to treatment and adequate follow-up in the injectable procaine benzylpenicillin-gentamicin group and 1145 (98%) infants in the oral amoxicillin group. In the procaine benzylpenicillin-gentamicin group, 234 infants (22%) failed treatment, compared with 221 (19%) infants in the oral amoxicillin group (risk difference -2·6%, 95% CI -6·0 to 0·8). Four infants died within 15 days of follow-up in each group. We detected no drug-related serious adverse events. INTERPRETATION: Young infants with fast breathing alone can be effectively treated with oral amoxicillin on an outpatient basis when referral to a hospital is not possible. FUNDING: Bill & Melinda Gates Foundation grant to WHO.