Incidence of possible serious bacterial infection in young infants in the three high-burden countries of the Democratic Republic of the Congo, Kenya, and Nigeria: A secondary analysis of a large, multi-country, multi-centre clinical trial.

Background: Neonatal infections are a major public health concern worldwide, particularly in low- and middle-income countries, where most of the infection-related deaths in under-five children occur. Sub-Saharan Africa has the highest mortality rates, but there is a lack of data on the incidence of sepsis from this region, hindering efforts to improve child survival. We aimed to determine the incidence of possible serious bacterial infection (PSBI) in young infants in three high-burden countries in Africa. Methods: This is a secondary analysis of data from the African Neonatal Sepsis (AFRINEST) trial, conducted in the Democratic Republic of the Congo (DRC), Kenya, and Nigeria between 15 March 2012 and 15 July 2013. We recorded baseline characteristics, the incidence of PSBI (as defined by the World Health Organization), and the incidence of local infections among infants from 0-59 days after birth. We report descriptive statistics. Results: The incidence of PSBI among 0-59-day-old infants across all three countries was 11.2% (95% confidence interval (CI) = 11.0-11.4). The DRC had the highest incidence of PSBI (19.0%; 95% CI = 18.2-19.8). Likewise, PSBI rates were higher in low birth weight infants (24.5%; 95% CI = 23.1-26.0) and infants born to mothers aged <20 years (14.1%; 95% CI = 13.4-14.8). The incidence of PSBI was higher among infants delivered at home (11.7%; 95% CI = 11.4-12.0). Conclusions: The high burden of PSBI among young infants in DRC, Kenya, and Nigeria demonstrates the importance of addressing PSBI in improving child survival in sub-Saharan Africa to reach the Sustainable Development Goals (SDGs). These data can support government authorities, policymakers, programme implementers, non-governmental organisations, and international partners in reducing preventable under-five deaths. Registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000286044.

Clinical and bacteriological profiles of neonatal sepsis in a tertiary hospital, south-western Nigeria.

Introduction: Antibiotic-resistant bacteria complicate treatment options in neonatal sepsis, especially in developing countries. This study determined the epidemiology and bacteriological characteristics of neonatal sepsis at a tertiary hospital, in southwest Nigeria. Methods: This was a cross-sectional study from December 2017 to April 2019 among admitted babies with clinical neonatal sepsis. Blood culture was performed by semi-automated system, sepsis biomarker assay (serum procalcitonin) by a semi-quantitative kit while proforma was used to capture clinico-demographic data. Bacterial identification, antibiotic susceptibility patterns, determination of genetic elements mediating resistance, were performed by standard methods and polymerase chain reaction protocols, respectively. Quantitative data were expressed as frequencies, mean; bivariate and multivariate analyses were performed by Chi-square or Fishers' exact test and logistic regression. Results: Of the 192 cases of neonatal sepsis enrolled, 42.7% (82/192) were blood culture positive. Factors associated with blood culture positivity included respiratory rate ≥60 bpm (60/82; p<0.03), lethargy/unconsciousness (59/82; FE=7.76; p<0.001), grunting respiration (54/82; p=0.04), meconium passage before birth (17/82; p=0.03) and prolonged rupture of membranes ≥24 hours (50/82; FE=6.90; p=0.01). On the other hand, mortality in the neonates was associated with elevated serum procalcitonin assay (>0.5 ng/mL) χ2=13.58; p=0.03] and Gram-negative bacteremia (χ2=24.64; p<0.001). The most common bacterial isolates were Staphylococcus aureus (42/82), coagulase-negative Staphylococcus spp. (17/82), Enterobacter spp. (8/82), and Acinetobacter spp. (6/82). Methicillin resistance was present in 85.7% (36/42) of Staphylococcus aureus and 52.9% (9/17) of coagulase-negative Staphylococcus, while extended-spectrum beta-lactamase (ESBL) and AmpC enzymes were present in (21.1%; 4/19) of the Gram-negative bacilli. Conclusions: Almost half of the cases of clinically diagnosed neonatal sepsis have bacterial etiologic confirmation of sepsis. Gram-negative bacteremia and high serum procalcitonin predict mortality in neonatal sepsis. There was high resistance to common antibiotics for the treatment of neonatal sepsis in our settings.

Rectal carriage of extended-spectrum ß-lactamase-producing Enterobacteriales among neonates admitted into a special care baby unit, southwest Nigeria.

BACKGROUND: The intestinal microbiota of neonates can be colonised by extended-spectrum ß-lactamase-producing Enterobacteriales (ESBL-PE) with the risks of subsequent infections. The antimicrobial resistance profile of the gut flora of neonates is not well defined in Nigeria. This study determined the burden of rectal carriage of ESBL-PE among neonates. METHODS: We conducted a prospective longitudinal study among neonates admitted into a tertiary hospital from September 2019 to November 2019. Stools were sampled at admission and weekly until exit and processed by standard laboratory methods including polymerase chain reaction to identify ESBL genes. The ESBL-PE colonisation period prevalence at admission and acquisition rate were determined. RESULTS: The period prevalence of the ESBL-PE colonisation and acquisition rate were 46.5% (59/127) and 34.6% (36/104), respectively. Prolonged rupture of the amniotic membrane (PROM; >24 h; p=0.004, odds ratio [OR] 0.297), number of neonates on admission in the same room (p<0.001, OR 0.053) and presence of an ESBL-PE colonisers (p=0.004, OR 0.272) were independent risk factors for ESBL-PE rectal colonisation. ESBL-PE colonisation did not correlate with mortality (Fisher's exact test 1.342, p=0.196). CONCLUSIONS: The rate of ESBL-PE neonatal rectal colonisation is high in our settings and this underscores the need for a review of neonatal admission protocols, embracing of antibiotic stewardship in the management of PROM, resistance surveillance and implementation of infection prevention and control in the neonatal unit.

Oral amoxicillin plus gentamicin regimens may be superior to the procaine-penicillin plus gentamicin regimens for treatment of young infants with possible serious bacterial infection when referral is not feasible: Pooled analysis from three trials in Africa and Asia.

Background: Hospital referral and admission in many- low and middle-income countries are not feasible for many young infants with sepsis/possible serious bacterial infection (PSBI). The effectiveness of simplified antibiotic regimens when referral to a hospital was not feasible has been shown before. We analysed the pooled data from the previous trials to compare the risk of poor clinical outcome for young infants with PSBI with the two regimens containing injectable procaine penicillin and gentamicin with the oral amoxicillin plus gentamicin regimen currently recommended by the World Health Organization (WHO) when referral is not feasible. Methods: Infant records from three individually randomised trials conducted in Africa and Asia were collated in a standard format. All trials enrolled young infants aged 0-59 days with any sign of PSBI (fever, hypothermia, stopped feeding well, movement only when stimulated, or severe chest indrawing). Eligible young infants whose caretakers refused hospital admission and consented were enrolled and randomised to a trial reference arm (arm A: procaine benzylpenicillin and gentamicin) or two experimental arms (arm B: oral amoxicillin and gentamicin or arm C: procaine benzylpenicillin and gentamicin initially, followed by oral amoxicillin). We compared the rate of poor clinical outcomes by day 15 (deaths till day 15, treatment failure by day 8, and relapse between day 9 and 15) in reference arm A with experimental arms and present risk differences with 95% confidence interval (CI), adjusted for trial. Results: A total of 7617 young infants, randomised to arm A, arm B, or arm C in the three trials, were included in this analysis. Most were 7-59 days old (71%) and predominately males (56%). Slightly over one-fifth of young infants had more than one sign of PSBI at the time of enrolment. Severe chest indrawing (45%), fever (43%), and feeding problems (25%) were the most common signs. Overall, those who received arm B had a lower risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -2.1%, 95% CI = -3.8%, -0.4%; P = 0.016) and intention-to-treat (risk difference = -1.8%, 95% CI = -3.5%, -0.2%; P = 0.031) analyses. Those who received arm C did not have an increased risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -1.1%, 95% CI = -2.8%, 0.6%) and intention-to-treat (risk difference = -0.8%, 95% CI = -2.5%, 0.9%) analyses. Overall, those who received arm B had a lower risk of poor clinical outcome compared to the combined arms A and C for both per-protocol (risk difference = -1.6%, 95% CI = -3.5%, -0.1%; P = 0.035) and intention-to-treat (risk difference = -1.4%, 95% CI = -2.8%, -0.1%; P = 0.049) analyses. Conclusions: Analysis of pooled individual patient-level data from three large trials in Africa and Asia showed that the WHO-recommended simplified antibiotic regimen B (oral amoxicillin and injection gentamicin) was superior to regimen A (injection procaine penicillin and injection gentamicin) and combined arms A and C (injection procaine penicillin and injection gentamicin, followed by oral amoxicillin) in terms of poor clinical outcome for the outpatient treatment of young infants with PSBI when inpatient treatment was not feasible. Registration: AFRINEST study [9] is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12610000286044. SATT Bangladesh study [10] is registered with ClinicalTrials.gov: NCT00844337. SATT Pakistan study [11] is registered at ClinicalTrials.gov: NCT01027429.

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.

Strengthening retinopathy of prematurity screening and treatment services in Nigeria: a case study of activities, challenges and outcomes 2017-2020.

OBJECTIVES: Retinopathy of prematurity (ROP) will become a major cause of blindness in Nigerian children unless screening and treatment services expand. This article aims to describe the collaborative activities undertaken to improve services for ROP between 2017 and 2020 as well as the outcome of these activities in Nigeria. DESIGN: Descriptive case study. SETTING: Neonatal intensive care units in Nigeria. PARTICIPANTS: Staff providing services for ROP, and 723 preterm infants screened for ROP who fulfilled screening criteria (gestational age <34 weeks or birth weight ≤2000 g, or sickness criteria). METHODS AND ANALYSIS: A WhatsApp group was initiated for Nigerian ophthalmologists and neonatologists in 2018. Members participated in a range of capacity-building, national and international collaborative activities between 2017 and 2018. A national protocol for ROP was developed for Nigeria and adopted in 2018; 1 year screening outcome data were collected and analysed. In 2019, an esurvey was used to collect service data from WhatsApp group members for 2017-2018 and to assess challenges in service provision. RESULTS: In 2017 only six of the 84 public neonatal units in Nigeria provided ROP services; this number had increased to 20 by 2018. Of the 723 babies screened in 10 units over a year, 127 (17.6%) developed any ROP; and 29 (22.8%) developed type 1 ROP. Only 13 (44.8%) babies were treated, most by intravitreal bevacizumab. The screening criteria were revised in 2020. Challenges included lack of equipment to regulate oxygen and to document and treat ROP, and lack of data systems. CONCLUSION: ROP screening coverage and quality improved after national and international collaborative efforts. To scale up and improve services, equipment for neonatal care and ROP treatment is urgently needed, as well as systems to monitor data. Ongoing advocacy is also essential.

Clinical signs of possible serious infection and associated mortality among young infants presenting at first-level health facilities.

BACKGROUND: The World Health Organization recommends inpatient hospital treatment of young infants up to two months old with any sign of possible serious infection. However, each sign may have a different risk of death. The current study aims to calculate the case fatality ratio for infants with individual or combined signs of possible serious infection, stratified by inpatient or outpatient treatment. METHODS: We analysed data from the African Neonatal Sepsis Trial conducted in five sites in the Democratic Republic of the Congo, Kenya and Nigeria. Trained study nurses classified sick infants as pneumonia (fast breathing in 7-59 days old), severe pneumonia (fast breathing in 0-6 days old), clinical severe infection [severe chest indrawing, high (> = 38°C) or low body temperature (<35.5°C), stopped feeding well, or movement only when stimulated] or critical illness (convulsions, not able to feed at all, or no movement at all), and referred them to a hospital for inpatient treatment. Infants whose caregivers refused referral received outpatient treatment. The case fatality ratio by day 15 was calculated for individual and combined clinical signs and stratified by place of treatment. An infant with signs of clinical severe infection or severe pneumonia was recategorised as having low- (case fatality ratio ≤2%) or moderate- (case fatality ratio >2%) mortality risk. RESULTS: Of 7129 young infants with a possible serious infection, fast breathing (in 7-59 days old) was the most prevalent sign (26%), followed by high body temperature (20%) and severe chest indrawing (19%). Infants with pneumonia had the lowest case fatality ratio (0.2%), followed by severe pneumonia (2.0%), clinical severe infection (2.3%) and critical illness (16.9%). Infants with clinical severe infection had a wide range of case fatality ratios for individual signs (from 0.8% to 11.0%). Infants with pneumonia had similar case fatality ratio for outpatient and inpatient treatment (0.2% vs. 0.3%, p = 0.74). Infants with clinical severe infection or severe pneumonia had a lower case fatality ratio among those who received outpatient treatment compared to inpatient treatment (1.9% vs. 6.5%, p<0.0001). We recategorised infants into low-mortality risk signs (case fatality ratio ≤2%) of clinical severe infection (high body temperature, or severe chest indrawing) or severe pneumonia and moderate-mortality risk signs (case fatality ratio >2%) (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection). We found that both categories had four times lower case fatality ratio when treated as outpatient than inpatient treatment, i.e., 1.0% vs. 4.0% (p<0.0001) and 5.3% vs. 22.4% (p<0.0001), respectively. In contrast, infants with signs of critical illness had nearly two times higher case fatality ratio when treated as outpatient versus inpatient treatment (21.7% vs. 12.1%, p = 0.097). CONCLUSIONS: The mortality risk differs with clinical signs. Young infants with a possible serious infection can be grouped into those with low-mortality risk signs (high body temperature, or severe chest indrawing or severe pneumonia); moderate-mortality risk signs (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection), or high-mortality risk signs (signs of critical illness). New treatment strategies that consider differential mortality risks for the place of treatment and duration of inpatient treatment could be developed and evaluated based on these findings. CLINICAL TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

Immediate "Kangaroo Mother Care" and Survival of Infants with Low Birth Weight.

BACKGROUND: "Kangaroo mother care," a type of newborn care involving skin-to-skin contact with the mother or other caregiver, reduces mortality in infants with low birth weight (<2.0 kg) when initiated after stabilization, but the majority of deaths occur before stabilization. The safety and efficacy of kangaroo mother care initiated soon after birth among infants with low birth weight are uncertain. METHODS: We conducted a randomized, controlled trial in five hospitals in Ghana, India, Malawi, Nigeria, and Tanzania involving infants with a birth weight between 1.0 and 1.799 kg who were assigned to receive immediate kangaroo mother care (intervention) or conventional care in an incubator or a radiant warmer until their condition stabilized and kangaroo mother care thereafter (control). The primary outcomes were death in the neonatal period (the first 28 days of life) and in the first 72 hours of life. RESULTS: A total of 3211 infants and their mothers were randomly assigned to the intervention group (1609 infants with their mothers) or the control group (1602 infants with their mothers). The median daily duration of skin-to-skin contact in the neonatal intensive care unit was 16.9 hours (interquartile range, 13.0 to 19.7) in the intervention group and 1.5 hours (interquartile range, 0.3 to 3.3) in the control group. Neonatal death occurred in the first 28 days in 191 infants in the intervention group (12.0%) and in 249 infants in the control group (15.7%) (relative risk of death, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P = 0.001); neonatal death in the first 72 hours of life occurred in 74 infants in the intervention group (4.6%) and in 92 infants in the control group (5.8%) (relative risk of death, 0.77; 95% CI, 0.58 to 1.04; P = 0.09). The trial was stopped early on the recommendation of the data and safety monitoring board owing to the finding of reduced mortality among infants receiving immediate kangaroo mother care. CONCLUSIONS: Among infants with a birth weight between 1.0 and 1.799 kg, those who received immediate kangaroo mother care had lower mortality at 28 days than those who received conventional care with kangaroo mother care initiated after stabilization; the between-group difference favoring immediate kangaroo mother care at 72 hours was not significant. (Funded by the Bill and Melinda Gates Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12618001880235; Clinical Trials Registry-India number, CTRI/2018/08/015369.).

Small and sick newborn care during the COVID-19 pandemic: global survey and thematic analysis of healthcare providers' voices and experiences.

INTRODUCTION: The COVID-19 pandemic is disrupting health systems globally. Maternity care disruptions have been surveyed, but not those related to vulnerable small newborns. We aimed to survey reported disruptions to small and sick newborn care worldwide and undertake thematic analysis of healthcare providers' experiences and proposed mitigation strategies. METHODS: Using a widely disseminated online survey in three languages, we reached out to neonatal healthcare providers. We collected data on COVID-19 preparedness, effects on health personnel and on newborn care services, including kangaroo mother care (KMC), as well as disruptors and solutions. RESULTS: We analysed 1120 responses from 62 countries, mainly low and middle-income countries (LMICs). Preparedness for COVID-19 was suboptimal in terms of guidelines and availability of personal protective equipment. One-third reported routine testing of all pregnant women, but 13% had no testing capacity at all. More than 85% of health personnel feared for their own health and 89% had increased stress. Newborn care practices were disrupted both due to reduced care-seeking and a compromised workforce. More than half reported that evidence-based interventions such as KMC were discontinued or discouraged. Separation of the mother-baby dyad was reported for both COVID-positive mothers (50%) and those with unknown status (16%). Follow-up care was disrupted primarily due to families' fear of visiting hospitals (~73%). CONCLUSION: Newborn care providers are stressed and there is lack clarity and guidelines regarding care of small newborns during the pandemic. There is an urgent need to protect life-saving interventions, such as KMC, threatened by the pandemic, and to be ready to recover and build back better.

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.

Preterm care during the COVID-19 pandemic: A comparative risk analysis of neonatal deaths averted by kangaroo mother care versus mortality due to SARS-CoV-2 infection.

BACKGROUND: COVID-19 is disrupting health services for mothers and newborns, particularly in low- and middle-income countries (LMIC). Preterm newborns are particularly vulnerable. We undertook analyses of the benefits of kangaroo mother care (KMC) on survival among neonates weighing ≤2000 g compared with the risk of SARS-CoV-2 acquired from infected mothers/caregivers. METHODS: We modelled two scenarios over 12 months. Scenario 1 compared the survival benefits of KMC with universal coverage (99%) and mortality risk due to COVID-19. Scenario 2 estimated incremental deaths from reduced coverage and complete disruption of KMC. Projections were based on the most recent data for 127 LMICs (~90% of global births), with results aggregated into five regions. FINDINGS: Our worst-case scenario (100% transmission) could result in 1,950 neonatal deaths from COVID-19. Conversely, 125,680 neonatal lives could be saved with universal KMC coverage. Hence, the benefit of KMC is 65-fold higher than the mortality risk of COVID-19. If recent evidence of 10% transmission was applied, the ratio would be 630-fold. We estimated a 50% reduction in KMC coverage could result in 12,570 incremental deaths and full disruption could result in 25,140 incremental deaths, representing a 2·3-4·6% increase in neonatal mortality across the 127 countries. INTERPRETATION: The survival benefit of KMC far outweighs the small risk of death due to COVID-19. Preterm newborns are at risk, especially in LMICs where the consequences of disruptions are substantial. Policymakers and healthcare professionals need to protect services and ensure clearer messaging to keep mothers and newborns together, even if the mother is SARS-CoV-2-positive. FUNDING: Eunice Kennedy Shriver National Institute of Child Health & Human Development; Bill & Melinda Gates Foundation; Elma Philanthropies; Wellcome Trust; and Joint Global Health Trials scheme of Department of Health and Social Care, Department for International Development, Medical Research Council, and Wellcome Trust.

Prevalence of clinical signs of possible serious bacterial infection and mortality associated with them from population-based surveillance of young infants from birth to 2 months of age.

BACKGROUND: Community-based data on the prevalence of clinical signs of possible serious bacterial infection (PSBI) and the mortality associated with them are scarce. The aim was to examine the prevalence for each sign of infection and mortality associated with infants in the first two months of life, using community surveillance through community health workers (CHW). METHODS: We used population-based surveillance data of infants up to two months of age from the African Neonatal Sepsis Trial (AFRINEST). In this study, CHWs visited infants up to 10 times during the first two months of life at five sites in three sub-Saharan African countries. CHW assessed the infant for signs of infection (local or systemic) and referred infants who presented with any sign of infection to a health facility. We used a longitudinal analysis to calculate the risk of death associated with the presence of a sign of infection at the time of the visit until the subsequent visit. RESULTS: During the first two months of their life, CHWs visited 84,759 live-born infants at least twice. In 11,089 infants (13.1%), one or more signs of infection were identified, of which 237 (2.1%) died. A sign of infection was detected at 2.1% of total visits. In 52% of visits, infants had one or more sign of systemic infection, while 25% had fast breathing in 7-59 days period and 23% had a local infection. All signs of infection, including multiple signs, were more frequently seen in the first week of life. The risk of mortality was very low (0.2%) for local infections and fast breathing in 7-59 days old, it was low for fast breathing 0-6 days old (0.6%), high body temperature (0.7%) and severe chest indrawing (1.0%), moderate for low body temperature (4.9%) and stopped feeding well/not able to feed at all (5.0%) and high for movement only when stimulated or no movement at all (10%) and multiple signs of systemic infection (15.5%). The risk of death associated with most clinical signs was higher (1.5 to 9 times) in the first week of life than at later age, except for low body temperature (4 times lower) as well as high body temperature (2 times lower). CONCLUSION: Signs of infections are common in the first two months of life. The mortality risk differs with clinical signs and can be grouped as very low (local infections, fast breathing 7-59 days), low (fever, severe chest indrawing and fast breathing 0-6 days), moderate (low body temperature and stopped feeding well/not able to feed at all) and high (for movements only on stimulation or no movements at all and multiple signs of infection). New treatment strategies that consider differential mortality risk could be developed and evaluated based on these findings. CLINICAL TRIAL REGISTRATION: The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

Unmet need for contraception among HIV-positive women in Ile-Ife, Nigeria.

As mother-to-child transmission of HIV is difficult to predict and also hard to prevent in practice, pregnancy among women living with HIV/AIDS (WHA) needs to be taken with considerable aforethought. The prevention of unwanted pregnancy among WHA is therefore a public health issue. The aim of our study was to determine the unmet need for contraception among HIV-positive women and the associated factors. Ours was a cross-sectional study involving 425 non-pregnant WHA attending an adult HIV clinic in Nigeria. Interviewer-administered, structured questionnaires designed for the study were used to obtain data. The contraceptive uptake was 47% while the unmet need for contraception was 20%. There were significant associations between unmet need for contraception and age group ( P < 0.001), religion ( P < 0.001), ethnic group ( P < 0.001), knowledge about contraceptives ( P = 0.02), educational status ( P = 0.01) and partners' retroviral status ( P = 0.008) The unmet need for contraception was high. Advocacy programs should perhaps be focused on older women, Christians and those with little or no education.

Antenatal corticosteroids for women at risk of imminent preterm birth in low-resource countries: the case for equipoise and the need for efficacy trials.

The scientific basis for antenatal corticosteroids (ACS) for women at risk of preterm birth has rapidly changed in recent years. Two landmark trials-the Antenatal Corticosteroid Trial and the Antenatal Late Preterm Steroids Trial-have challenged the long-held assumptions on the comparative health benefits and harms regarding the use of ACS for preterm birth across all levels of care and contexts, including resource-limited settings. Researchers, clinicians, programme managers, policymakers and donors working in low-income and middle-income countries now face challenging questions of whether, where and how ACS can be used to optimise outcomes for both women and preterm newborns. In this article, we briefly present an appraisal of the current evidence around ACS, how these findings informed WHO's current recommendations on ACS use, and the knowledge gaps that have emerged in the light of new trial evidence. Critical considerations in the generalisability of the available evidence demonstrate that a true state of clinical equipoise exists for this treatment option in low-resource settings. An expert group convened by WHO concluded that there is a clear need for more efficacy trials of ACS in these settings to inform clinical practice.

The Impact of Structured Mentor Mother Programs on Presentation for Early Infant Diagnosis Testing in Rural North-Central Nigeria: A Prospective Paired Cohort Study.

BACKGROUND: Early infant diagnosis (EID) by 2 months of age is an important prevention of mother-to-child cascade step that serves as an early postpartum indicator of program success. Uptake and timely presentation for infant HIV diagnosis are significant challenges in resource-limited settings. Few studies on maternal peer support (PS) have demonstrated impact on EID. The MoMent study evaluated the impact of structured PS on timely presentation for EID testing in rural North-Central Nigeria. METHODS: A total of 497 HIV-positive pregnant women were consecutively recruited at 10 primary health care centers with structured, closely supervised Mentor Mother (MM) support, and 10 pair-matched primary health care centers with routine but ad hoc PS. EID was assessed among HIV-exposed infants delivered to recruited women, and was defined by presentation for DNA polymerase chain reaction testing between 35 and 62 days of life. A logistic regression model with generalized estimating equation to account for clustering was used to assess the effect of MMs on EID presentation. RESULTS: Data from 408 live-born infants were available for analysis. Exposure to MM support was associated with higher odds of timely EID presentation among infants, compared with routine PS (adjusted odds ratios = 3.7, 95% confidence interval: 2.8 to 5.0). CONCLUSIONS: Closely supervised, organized MM support significantly improved presentation for EID among HIV-exposed infants in a rural Nigerian setting. Structured PS can improve rates of timely EID presentation and potentially the uptake of EID testing in resource-limited settings.

Current Neonatal Skin Care Practices in Four African Sites.

Data for this study on skin care practices and emollient use in four African sites were collected using in-depth interviews, focus-group discussions and observations. Respondents were mothers, grandmothers, fathers, health workers, birth attendants and people selling skin-care products. Analysis included content and framework analyses.Emollient use was a normative practice in all sites, with frequent application from an early age in most sites. There were variations in the type of emollients used, but reasons for use were similar and included improving the skin, keeping the baby warm, softening/strengthening the joints/bones, shaping the baby, ensuring flexibility and encouraging growth and weight gain. Factors that influenced emollient choice varied and included social pressure, cost, availability and deep-rooted traditional norms. Massage associated with application was strong and potentially damaging to the skin in some sites.Given the widespread use of emollients, the repeated exposure of newborns in the first month of life and the potential impact of emollients on mortality, trials such as those that have been conducted in Asia are needed in a range of African settings.

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.

Early neonatal bilirubin, hematocrit, and glucose-6-phosphate dehydrogenase status.

OBJECTIVE: To document the patterns of bilirubin and hematocrit values among glucose-6-phosphate dehydrogenase (G6PD)-deficient and G6PD-normal Nigerian neonates in the first week of life, in the absence of exposure to known icterogenic agents. METHODS: The G6PD status of consecutive term and near-term neonates was determined, and their bilirubin levels and hematocrits were monitored during the first week of life. Infants were stratified into G6PD deficient, intermediate, and normal on the basis of the modified Beutler's fluorescent spot test. Means of total serum bilirubin (TSB) and hematocrits of the 3 groups of infants were compared. RESULTS: The 644 neonates studied comprised 353 (54.8%) boys and 291 (45.2%) girls and 540 (83.9%) term and 104 (16.1%) near-term infants. They consisted of 129 (20.0%) G6PD-deficient, 69 (10.7%) G6PD-intermediate, and 446 (69.3%) G6PD-normal neonates. The G6PD-deficient and G6PD-intermediate infants had higher mean TSB than their G6PD-normal counterparts at birth and throughout the first week of life (P < .001). Mean peak TSB levels were 14.1 (9.48), 10.2 (3.8), and 6.9 (3.3) mg/dL for G6PD-deficient, G6PD-intermediate, and G6PD-normal neonates, respectively. Peak TSB was attained on approximately day 4 in all 3 groups, and trends in TSB were similar. Mean hematocrits at birth were similar in the 3 G6PD groups. However, G6PD-deficient and -intermediate infants had higher declines in hematocrit, bilirubin levels, and need for phototherapy than G6PD-normal infants (P < .001). CONCLUSIONS: The G6PD-deficient and G6PD-intermediate neonates had a higher risk of neonatal hyperbilirubinemia and would therefore need greater monitoring in the first week of life, even without exposure to known icterogenic agents.