Simplified Regimens for Management of Neonates and Young Infants With Severe Infection When Hospital Admission Is Not Possible

Background: In resource-limited settings, most young infants with signs of severe infection do not receive the recommended inpatient treatment with intravenous broad spectrum antibiotics for 10 days or more because such treatment is not accessible, acceptable or affordable to families. This trial was initiated in the Democratic Republic of Congo, Kenya and Nigeria to assess the safety and efficacy of simplified treatment regimens for the young infants with signs of severe infection who cannot receive hospital care. Methods: This is a randomized, open-label equivalence trial in which 3600 young infants with signs of clinical severe infection will be enrolled. The primary outcome is treatment failure in 7 days after enrollment, which includes death or worsening of the clinical condition on any day, or no improvement in the clinical condition by day 4 of treatment. Secondary outcomes include compliance with study therapy, adverse effects due to the study drugs and relapse or death during the week after completion of treatment. Discussion: The results of this study, along with ongoing studies in Pakistan and Bangladesh, will inform the development of global policy for treatment of severe neonatal infections in resource-limited settings

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

An open randomized clinical trial in comparing two artesunate-based combination treatments on Plasmodium falciparum malaria in Nigerian children: artesunate/sulphamethoxypyrazine/pyrimethamine (fixed dose over 24 hours) versus artesunate/amodiaquine (fixed dose over 48 hours)

<p>Abstract</p> <p>Background</p> <p>Several studies have demonstrated the efficacy of artemisinin-combination therapy (ACT) across malaria zones of the world. Fixed dose ACT with shorter courses and fewer tablets may be key determinants to ease of administration and compliance.</p> <p>Methods</p> <p>Children aged one year to 13 years presenting with uncomplicated <it>Plasmodium falciparum </it>malaria were recruited in Ibadan, south-western Nigeria. A total of 250 children each were randomly assigned to receive three doses of artesunate/sulphamethoxypyrazine/pyrimethamine (AS + SMP) (12 hourly doses over 24 hours) or three doses of artesunate/amodiaquine (AS + AQ) (daily doses over 48 hours). Efficacy and safety of the two drugs were assessed using a 28-day follow-up and the primary outcome was PCR- corrected parasitological cure rate and clinical response.</p> <p>Results</p> <p>There were two (0.4%) early treatment failures, one in each treatment arm. The PCR corrected cure rates for day 28 was 97.9% in the AS + AQ arm and 95.6% in the AS + SMP arm (p = 0.15). The re-infection rate was 1.7% in the AS + AQ arm and 5.7% in the AS + SMP arm (p = 0.021). The fever clearance time was similar in the two treatment groups: 1 - 2 days for both AS + SMP and AS + AQ (p = 0.271). The parasite clearance time was also similar in the two treatment groups with 1 - 7 days for AS + SMP and 1 - 4 days for AS + AQ (p = 0.941). The proportion of children with gametocytes over the follow-up period was similar in both treatment groups. Serious Adverse Events were not reported in any of the patients and in all children, laboratory values (packed cell volume, liver enzymes, bilirubin) remained within normal levels during the follow-up period but the packed cell volume was significantly lower in the AS + SMP group.</p> <p>Conclusions</p> <p>This study demonstrates that AS + SMP FDC given as three doses over 24 hours (12-hour intervals) has similar efficacy as AS + AQ FDC given as three doses over 48 hours (24-hour interval) for the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria in children in Nigeria. Both drugs also proved to be safe. Therefore, AS + SMP could be an alternative to currently recommended first-line ACT with continuous resistance surveillance.</p

New World Health Organization recommendations for care of preterm or low birth weight infants: health policy

Approximately 11% of infants are born preterm, and complications of prematurity are the most common cause of death in children aged under five years. Almost one million preterm infants die each year across low, high and middle income countries. In 2021, the World Health Organization (WHO) convened a Guideline Development Group (GDG) to examine evidence and formulate recommendations for care of preterm or low birthweight (LBW) infants according to WHO Guideline Review Committee (GRC) criteria. GRADE methods were used to assess the certainty of evidence and the GDG developed judgements using the DECIDE (Developing and Evaluating Communication strategies to support Informed Decisions and practice based on Evidence) framework. Twenty-five recommendations were made; 11 recommendations were new, and 16 were for preventive and promotive care. Kangaroo Mother Care (KMC) was recommended to start immmediately after birth as routine care for all preterm or LBW newborns (except for critically ill infants who are in shock, unable to breath spontaneously after resuscitation, or require ventilatory support) both in the facility and at home. New recommendations were also made for caffeine to treat apnoea and for extubation; family involvement in routine care for preterm or LBW infants; and for post-discharge home-visit follow-up care. New recommendations were also made to consider use of probiotics, emollient therapy, caffeine for prevention of apnoea, continuous positive airway pressure (CPAP) immediately after birth (with or without respiratory distress) in infants less than 32 weeks gestational age; and for family support to enable the care of preterm or LBW infants. The recommendations confirm the pivotal role of preventive and promotive care for preterm and LBW infants, especially the importance of keeping the baby and mother together, and empowering and supporting families to care for their preterm or LBW infant. WHO is now working to help scale up care for small and sick newborns, including organizational shifts in all ‘health system building blocks’ such as infrastructure, commodities, workforce and monitoring

Research priorities for care of preterm or low birth weight infants: health policy

Research priorities for preterm or low birth weight (LBW) infants were advanced in 2012, and other research priority-setting exercises since then have included more limited, context-specific research priorities pertaining to preterm infants. While developing new World Health Organization (WHO) guidelines for care of preterm or LBW infants, we conducted a complementary research prioritisation exercise. A diverse, globally representative guideline development group (GDG) of experts – all authors of this paper along with WHO steering group for preterm-LBW guidelines – was assembled by the WHO to examine evidence and consider a variety of factors in intervention effectiveness and implementation, leading to 25 new recommendations and one good practice statement for care of preterm or LBW infants. The GDG generated research questions (RQs) based on contributions to improvements in care and outcomes of preterm or LBW infants, public health impacts, answerability, knowledge gaps, feasibility of implementation, and promotion of equity, and then ranked the RQs based on their likelihood to further change or influence the WHO guidelines for the care of preterm or LBW infants in the future. Thirty-six priority RQs were identified, 32 (89%) of which focused on aspects of intervention effectiveness, and the remaining four addressed implementation (“how”) questions. Of the top 12 RQs, seven focused on further advancing new recommendations – such as family involvement and support in caring for preterm or LBW infants, emollient therapy, probiotics, immediate KMC for critically ill newborns, and home visits for post-discharge follow-up of preterm or LBW infants – and three RQs addressed issues of feeding (breastmilk promotion, milk banks, individualized feeding). RQs prioritised here will be critical for optimising the effectiveness and delivery of new WHO recommendations for care of preterm or LBW infants. The RQs encompass unanswered research priorities for preterm or LBW infants from prior prioritisation exercises which were conducted using Child Health and Nutrition Research Initiative (CHNRI) methodology

Management of possible serious bacterial infection in young infants where referral is not possible in the context of existing health system structure in Ibadan, South-west Nigeria.

IntroductionNeonatal infections contribute substantially to infant mortality in Nigeria and globally. Management requires hospitalization, which is not accessible to many in low resource settings. World Health Organization developed a guideline to manage possible serious bacterial infection (PSBI) in young infants up to two months of age when a referral is not feasible. We evaluated the feasibility of implementing this guideline to achieve high coverage of treatment.MethodsThis implementation research was conducted in out-patient settings of eight primary health care centres (PHC) in Lagelu Local Government Area (LGA) of Ibadan, Oyo State, Nigeria. We conducted policy dialogue with the Federal and State officials to adopt the WHO guideline within the existing programme setting and held orientation and sensitization meetings with communities. We established a Technical Support Unit (TSU), built the capacity of health care providers, supervised and mentored them, monitored the quality of services and collected data for management and outcomes of sick young infants with PSBI signs. The Primary Health Care Directorate of the state ministry and the local government led the implementation and provided technical support. The enablers and barriers to implementation were documented.ResultsFrom 1 April 2016 to 31 July 2017 we identified 5278 live births and of these, 1214 had a sign of PSBI. Assuming 30% of births were missed due to temporary migration to maternal homes for delivery care and approximately 45% cases came from outside the catchment area due to free availability of medicines, the treatment coverage was 97.3% (668 cases/6861 expected births) with an expected 10% PSBI prevalence within the first 2 months of life. Of 1214 infants with PSBI, 392 (32%) infants 7-59 days had only fast breathing (pneumonia), 338 (27.8%) infants 0-6 days had only fast breathing (severe pneumonia), 462 (38%) presented with signs of clinical severe infection (CSI) and 22 (1.8%) with signs of critical illness. All but two, 7-59 days old infants with pneumonia were treated with oral amoxicillin without a referral; 80% (312/390) adhered to full treatment; 97.7% (381/390) were cured, and no deaths were reported. Referral to the hospital was not accepted by 87.7% (721/822) families of infants presenting with signs of PSBI needing hospitalization (critical illness 5/22; clinical severe infection; 399/462 and severe pneumonia 317/338). They were treated on an outpatient basis with two days of injectable gentamicin and seven days of oral amoxicillin. Among these 81% (584/721) completed treatment; 97% (700/721) were cured, and three deaths were reported (two with critical illness and one with clinical severe infection). We identified health system gaps including lack of staff motivation and work strikes, medicines stockouts, sub-optimal home visits that affected implementation.ConclusionsWhen a referral is not feasible, outpatient treatment for young infants with signs of PSBI is possible within existing programme structures in Nigeria with high coverage and low case fatality. To scale up this intervention successfully, government commitment is needed to strengthen the health system, motivate and train health workers, provide necessary commodities, establish technical support for implementation and strengthen linkages with communities.RegistrationTrial is registered on Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001373369