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The coverage of community-based maternal, neonatal, and child health (MNCH) services remains low, especially in hard-to-reach areas. We evaluated the effectiveness of a mobile-phone-and web-based application, Innovative Mobile-phone Technology for Community Health Operations (ImTeCHO), as a job aid to the government's Accredited Social Health Activists (ASHAs) and Primary Health Center (PHC) staff to improve coverage of MNCH services in rural tribal communities of Gujarat, India. This open cluster-randomized trial was conducted in 22 PHCs in six tribal blocks of Bharuch and Narmada districts in India. The ImTeCHO mobile-phone-and web-based application included various technology-based job aids to facilitate scheduling of home visits, screening for complications, counseling during home visits, and supportive supervision by PHC staff. Primary outcome indicators were a composite index calculated based on coverage of important MNCH services and coverage of at least two home visitations by ASHA within the first week of birth. Primary analysis was intention to treat (ITT). Generalized Estimating Equation (GEE) was used to account for clustering. Eleven PHCs each were randomly allocated to the intervention (280 ASHAs, population: 234,134) and control (281 ASHAs, population: 242,809) arms. The intervention was implemented from February, 2016 to January, 2017. At the end of the implementation, 6,493 mothers were surveyed. Most of the surveyed women were tribal (5,571, 85.8%), and reported having a government-issued certificate for living below poverty line (4,916, 75.7%). The coverage of at least two home visits within first week of birth was 32.4% in the intervention clusters compared to 22.9% in the control clusters (adjusted effect size 10.2 [95% CI: 6.4, 14.0], p < 0.001). Mean number of home visits within first week of birth was 1.11 and 0.80 for intervention and control clusters, respectively (adjusted effect size 0.34 [95% CI: 0.23, 0.45], p < 0.001). The composite coverage index was 43.0% in the intervention clusters compared to 38.5% (adjusted effect size 4.9 [95% CI: 0.2, 9.5], p = 0.03) in the control clusters. There were substantial improvements in coverage home visits by ASHAs during antenatal period (adjusted effect size 15.7 [95% CI: 11.0, 20.4], p < 0.001), postnatal period (adjusted effect size 6.4, [95% CI: 3.2, 9.6], p <0.001), early initiation of breastfeeding (adjusted effect size 7.8 [95% CI: 4.2, 11.4], p < 0.001), and exclusive breastfeeding (adjusted effect size 13.4 [95% CI: 8.9, 17.9], p < 0.001). Number of infant and neonatal deaths was similar in the two arms in the ITT analysis. The limitations of the study include potential risk of inaccuracies in reporting events that occurred during pregnancy by the mothers and the duration of intervention being 12 months, which might be considered short. In this study, we found that use of ImTeCHO mobile- and web-based application as a job aid by government ASHAs and PHC staff improved coverage and quality of MNCH services in hard-to-reach areas. Supportive supervision, change management, and timely resolution of technology-related issues were critical implementation considerations to ensure adherence to the intervention. Study was registered at the Clinical Trial Registry of India (www.ctri.nic.in). Trial number: CTRI/2015/06/005847. The trial was registered (prospective) on 3 June, 2015. First enrollment was done on 26 August, 2015.

Improving oxygen systems may improve clinical outcomes for hospitalised children with acute lower respiratory infection (ALRI). This paper reports the effects of an improved oxygen system on mortality and clinical practices in 12 general, paediatric, and maternity hospitals in southwest Nigeria. We conducted an unblinded stepped-wedge cluster-randomised trial comparing three study periods: baseline (usual care), pulse oximetry introduction, and stepped introduction of a multifaceted oxygen system. We collected data from clinical records of all admitted neonates (<28 days old) and children (28 days to 14 years old). Primary analysis compared the full oxygen system period to the pulse oximetry period and evaluated odds of death for children, children with ALRI, neonates, and preterm neonates using mixed-effects logistic regression. Secondary analyses included the baseline period (enabling evaluation of pulse oximetry introduction) and evaluated mortality and practice outcomes on additional subgroups. Three hospitals received the oxygen system intervention at 4-month intervals. Primary analysis included 7,716 neonates and 17,143 children admitted during the 2-year stepped crossover period (November 2015 to October 2017). Compared to the pulse oximetry period, the full oxygen system had no association with death for children (adjusted odds ratio [aOR] 1.06; 95% confidence interval [CI] 0.77-1.46; p = 0.721) or children with ALRI (aOR 1.09; 95% CI 0.50-2.41; p = 0.824) and was associated with an increased risk of death for neonates overall (aOR 1.45; 95% CI 1.04-2.00; p = 0.026) but not preterm/low-birth-weight neonates (aOR 1.30; 95% CI 0.76-2.23; p = 0.366). Secondary analyses suggested that the introduction of pulse oximetry improved oxygen practices prior to implementation of the full oxygen system and was associated with lower odds of death for children with ALRI (aOR 0.33; 95% CI 0.12-0.92; p = 0.035) but not for children, preterm neonates, or neonates overall (aOR 0.97, 95% CI 0.60-1.58, p = 0.913; aOR 1.12, 95% CI 0.56-2.26, p = 0.762; aOR 0.90, 95% CI 0.57-1.43, p = 0.651). Limitations of our study are a lower-than-anticipated power to detect change in mortality outcomes (low event rates, low participant numbers, high intracluster correlation) and major contextual changes related to the 2016-2017 Nigerian economic recession that influenced care-seeking and hospital function during the study period, potentially confounding mortality outcomes. We observed no mortality benefit for children and a possible higher risk of neonatal death following the introduction of a multifaceted oxygen system compared to introducing pulse oximetry alone. Where some oxygen is available, pulse oximetry may improve oxygen usage and clinical outcomes for children with ALRI. Australian New Zealand Clinical Trials Registry: ACTRN12617000341325.

Research on simplified antibiotic regimens for outpatient treatment of 'Possible Serious Bacterial Infection' (PSBI) and the subsequent World Health Organization (WHO) guidelines provide an opportunity to increase treatment coverage. This multi-country implementation research initiative aimed to learn how to implement the WHO guideline in diverse contexts. These experiences have been individually published; this overview paper provides a summary of results and lessons learned across sites. A common mixed qualitative and quantitative methods protocol for implementation research was used in eleven sites in the Democratic Republic of Congo (Equateur province), Ethiopia (Tigray and Oromia regions), India (Haryana, Himachal Pradesh, Maharashtra, and Uttar Pradesh states), Malawi (Central Region), Nigeria (Kaduna and Oyo states), and Pakistan (Sindh province). Key steps in implementation research were: i) policy dialogue with the national government and key stakeholders, ii) the establishment of a 'Technical Support Unit' with the research team and district level managers, and iii) development of an implementation strategy and its refinement using an iterative process of implementation, programme learning and evaluation. All sites successfully developed and evaluated an implementation strategy to increase coverage of PSBI treatment. During the study period, a total of 6677 young infants from the study catchment area were identified and treated at health facilities in the study area as inpatients or outpatients among 88179 live births identified. The estimated coverage of PSBI treatment was 75.7% (95% CI 74.8% to 78.6%), assuming a 10% incidence of PSBI among all live births. The treatment coverage was variable, ranging from 53.3% in Lucknow, India to 97.3% in Ibadan, Nigeria. The coverage of inpatient treatment ranged from 1.9% in Zaria, Nigeria, to 33.9% in Tigray, Ethiopia. The outpatient treatment coverage ranged from 30.6% in Pune, India, to 93.6% in Zaria, Nigeria. Overall, the case fatality rate (CFR) was 14.6% (95% CI 11.5% to 18.2%) for 0-59-day old infants with critical illness, 1.9% (95% CI 1.5% to 2.4%) for 0-59-day old infants with clinical severe infection and 0.1% for fast breathing in 7-59 days old. Among infants treated as outpatients, CFR was 13.7% (95% CI 8.7% to 20.2%) for 0-59-day old infants with critical illness, 0.9% (95% CI 0.6% to 1.2%) for 0-59-day old infants with clinical severe infection, and 0.1% for infants 7-59 days old with fast breathing. Important lessons on how to conduct each step of implementation research, and the challenges and facilitators for implementation of PSBI management guideline in routine health systems are summarised and discussed. These lessons will be used to introduce and scale-up implementation in relevant Low- and middle-income countries.

Pneumonia is a leading global cause of morbidity and mortality in children younger than 5 years. In Pakistan, the proportion of deaths due to pneumonia is higher in rural areas than it is in urban areas, with a substantial proportion of individuals dying at home because referral for care is problematic in such areas. We aimed to establish whether community case identification and management of severe pneumonia by oral antibiotics delivered through community health workers has the potential to reduce the number of infants dying at home. We did a cluster-randomised controlled trial in Matiari district of rural Sindh, Pakistan. Public-sector lady health workers (LHWs) undertook community case management of WHO-defined severe pneumonia. The children in intervention clusters with suspected pneumonia were screened by LHWs and those diagnosed with severe pneumonia were prescribed oral amoxicillin syrup (90 mg/kg per day in two doses) for 5 days at home. Children in control clusters were given one dose of oral co-trimoxazole and were referred to their nearest health facility for admission and intravenous antibiotics, as per government policy. In both groups, follow-up visits at home were done at days 2, 3, 6, and 14 by LHW. The primary outcome was treatment failure by day 6 after enrolment. We matched and randomly allocated 18 clusters (union councils, the smallest administrative unit of the district) to either intervention and control using a computer-generated randomisation scheme. Analyses were done per-protocol. This trial is registered with ClinicalTrials.gov, number NCT01192789. 2341 children in intervention clusters and 2069 children in control clusters participated in the study, enrolled between Feb 13, 2008, and March 15, 2010. We recorded 187 (8%) treatment failures by day 6 in the intervention group and 273 (13%) in the control group. After adjusting for clustering, the risk difference for treatment failure was −5·2% (95% CI −13·7% to 3·3%). We recorded three deaths, two by day 6 and one between days 7 and 14. We recorded no serious adverse events. Public sector LHWs in Pakistan were able to satisfactorily diagnose and treat severe pneumonia at home in rural Pakistan. This strategy might effectively reach children with pneumonia in settings where referral is difficult, and it could be a key component of community detection and management strategies for childhood pneumonia. US Agency for International Development through grants to John Snow Incorporation and Boston University, USA.

The process was coordinated by the World Health Organization. * Forty-five leading childhood pneumonia researchers suggested more than 500 research ideas, which were merged into 158 research questions that spanned the broad spectrum of epidemiological research, health policy and systems research, improvement of existing interventions, and development of new interventions. * Within the short time frame in which gains were expected globally, the research priorities were dominated by health systems and policy research topics (e.g., studying barriers to health care seeking and access, as well as barriers to increased coverage with available vaccines; and evaluating the potential to safely scale up antibiotic treatment through community health workers). * These were followed by epidemiological questions to identify the main gaps in knowledge (e.g., predictors of severe pneumonia that requires hospitalisation); priorities for improvement of the existing interventions (e.g., training of community health workers to recognise danger signs, refer, and treat sick children); and identifying cost reduction mechanisms for the available conjugate vaccines. * Among the new interventions, the greatest support was shown for the development of low-cost conjugate vaccines and cross-protective common protein vaccines against the pneumococcus. Furthermore, pneumonia is recognised as a common and serious consequence of pandemic influenza, and preparedness for pandemic influenza should include prevention and control of pneumonia [11].\\n Dowell (Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America), Michael English (KEMRI/Wellcome Trust Research Programme, Nairobi, Kenya), Adegoke G. Falade (Department of Pediatrics, College of Medicine, University of Ibadan, Ibadan, Nigeria), Brian Greenwood (Department of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom), Rana Hajjeh (Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America), Tabish Hazir (Children's Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan), Patricia Hibberd (Division of Global Health, Department of Pediatrics, Massachussetts General Hospital, Boston, Massachusetts, United States of America), Stephen Howie (MRC Laboratories, Fajara, Banjul, The Gambia), Prakash M. Jeena (Department of Paediatrics and Child Health, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa), Karin Kallander (Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden), Keith Klugman (Hubert Department of Global Health, The Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America), Shabir Madhi (Respiratory and Meningeal Pathogens Research Unit, Chris Hani - Baragwanath Hospital, Bertsham Gauteng, South Africa), Kim Mulholland (Department of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom), Stephen K. Obaro (Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America), Stefan Peterson (Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden), Zeba Rasmussen (Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America), Anna Roca (University of Barcelona, Barcelona, Spain), H. P. S. Sachdev (Sitaram Bhartia Institute of Science and Research, New Delhi, India), Mathuram Santosham (Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America), Anne Schuchat (Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America), Donald M. Thea (Center for International Health, Boston University School of Public Health, Boston, Massachusetts, United States of America), and Paul Torzillo (R.P.A. Medical Centre, University of Sydney, Sydney, Australia).

First dose oral co-trimoxazole and referral are recommended for WHO-defined severe pneumonia. Difficulties with referral compliance are reported in many low-resource settings, resulting in low access to appropriate treatment. The objective in this study was to assess whether community case management by lady health workers (LHWs) with oral amoxicillin in children with severe pneumonia was equivalent to current standard of care. In Haripur district, Pakistan, 28 clusters were randomly assigned with stratification in a 1:1 ratio to intervention and control clusters by use of a computer-generated randomisation sequence. Children were included in the study if they were aged 2–59 months with WHO-defined severe pneumonia and living in the study area. In the intervention clusters, community-based LHWs provided mothers with oral amoxicillin (80–90 mg/kg per day or 375 mg twice a day for infants aged 2–11 months and 625 mg twice a day for those aged 12–59 months) with specific guidance on its use. In control clusters, LHWs gave the first dose of oral co-trimoxazole (age 2–11 months, sulfamethoxazole 200 mg plus trimethoprim 40 mg; age 12 months to 5 years, sulfamethoxazole 300 mg plus trimethoprim 60 mg) and referred the children to a health facility for standard of care. Participants, carers, and assessors were not masked to treatment assignment. The primary outcome was treatment failure by day 6. Analysis was per protocol with adjustment for clustering within groups by use of generalised estimating equations. This study is registered, number ISRCTN10618300. We assigned 1995 children to treatment in 14 intervention clusters and 1477 in 14 control clusters, and we analysed 1857 and 1354 children, respectively. Cluster-adjusted treatment failure rates by day 6 were significantly reduced in the intervention clusters (165 [9%] vs 241 [18%], risk difference −8·9%, 95% CI −12·4 to −5·4). Further adjustment for baseline covariates made little difference (−7·3%, −10·1 to −4·5). Two deaths were reported in the control clusters and one in the intervention cluster. Most of the risk reduction was in the occurrence of fever and lower chest indrawing on day 3 (−6·7%, −10·0 to −3·3). Adverse events were diarrhoea (n=4) and skin rash (n=1) in the intervention clusters and diarrhoea (n=3) in the control clusters. Community case management could result in a standardised treatment for children with severe pneumonia, reduce delay in treatment initiation, and reduce the costs for families and health-care systems. United States Agency for International Development (USAID).

Background An estimated 30 million neonates require inpatient care annually, many with life-threatening infections. Appropriate antibiotic management is crucial, yet there is no routine measurement of coverage. The Every Newborn Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study aimed to validate maternal and newborn indicators to inform measurement of coverage and quality of care. This paper reports validation of reported antibiotic coverage by exit survey of mothers for hospitalized newborns with clinically-defined infections, including sepsis, meningitis, and pneumonia. Methods EN-BIRTH study was conducted in five hospitals in Bangladesh, Nepal, and Tanzania (July 2017–July 2018). Neonates were included based on case definitions to focus on term/near-term, clinically-defined infection syndromes (sepsis, meningitis, and pneumonia), excluding major congenital abnormalities. Clinical management was abstracted from hospital inpatient case notes (verification) which was considered as the gold standard against which to validate accuracy of women’s report. Exit surveys were conducted using questions similar to The Demographic and Health Surveys (DHS) approach for coverage of childhood pneumonia treatment. We compared survey-report to case note verified, pooled across the five sites using random effects meta-analysis. Results A total of 1015 inpatient neonates admitted in the five hospitals met inclusion criteria with clinically-defined infection syndromes. According to case note verification, 96.7% received an injectable antibiotic, although only 14.5% of them received the recommended course of at least 7 days. Among women surveyed ( n  = 910), 98.8% (95% CI: 97.8–99.5%) correctly reported their baby was admitted to a neonatal ward. Only 47.1% (30.1–64.5%) reported their baby’s diagnosis in terms of sepsis, meningitis, or pneumonia. Around three-quarters of women reported their baby received an injection whilst in hospital, but 12.3% reported the correct antibiotic name. Only 10.6% of the babies had a blood culture and less than 1% had a lumbar puncture. Conclusions Women’s report during exit survey consistently underestimated the denominator (reporting the baby had an infection), and even more so the numerator (reporting known injectable antibiotics). Admission to the neonatal ward was accurately reported and may have potential as a contact point indicator for use in household surveys, similar to institutional births. Strengthening capacity and use of laboratory diagnostics including blood culture are essential to promote appropriate use of antibiotics. To track quality of neonatal infection management, we recommend using inpatient records to measure specifics, requiring more research on standardised inpatient records.

IntroductionStrategies for reducing infant mortality require accurate, local, population-level data. We conducted a population-based observational study in three countries in South Asia to describe risk factors, causes and rates of mortality in young infants.MethodsPregnancies, births and pregnancy outcomes were determined through household surveillance, and cause of deaths was ascertained by verbal autopsy. Cox regression was used to identify risk factors for deaths during days 0–<3, 3–<7 and 7–<60.ResultsAmong 73 622 pregnancy outcomes, 4638 deaths were identified, including 1669 stillbirths (36.0%), 1347 (29.0%) deaths among non-registered liveborn infants who died before the first home visit by community health workers (CHWs), and 1622 (35.0%) deaths that occurred during days 0–<60 among liveborn registered infants. Most deaths among liveborn infants (59.3%, 1757 of 2965) took place within 3 days of birth. The most common causes of death over the young infant period were infections/sepsis (32.5%, n=963 of 2,965), birth asphyxia (29.0%, n=859) and preterm birth/low birth weight (14.1%, n=418). Risk factors for mortality included early morbidity (need for resuscitation, intrapartum infection/antibiotics, multiple gestation, congenital anomalies), environmental factors (smoke exposure, maternal betel chewing) and poor maternal access to quality care (history of a prior neonatal death, lack of care seeking for labour complications). Protective factors included biology (female sex, higher birth weight), essential newborn care (immediate breastfeeding, clean cord care) and access to quality maternal and newborn care (antenatal care, facility birth, skilled birth attendant, maternal education, household wealth).ConclusionsOur population-based data highlight the importance of addressing deaths due to birth asphyxia and infections, while recognising that the relative burden of deaths due to preterm birth and congenital anomalies is increasing globally. Access to quality community-based and facility-based maternal and newborn care is critical to efforts to reduce mortality in young infants in high-mortality settings such as rural South Asia.

WHO case management guidelines for severe pneumonia involve referral to hospital for treatment with parenteral antibiotics. If equally as effective as parenteral treatment, home-based oral antibiotic treatment could reduce referral, admission, and treatment costs. Our aim was to determine whether home treatment with high-dose oral amoxicillin and inpatient treatment with parenteral ampicillin were equivalent for the treatment of severe pneumonia in children. This randomised, open-label equivalency trial was done at seven study sites in Pakistan. 2037 children aged 3–59 months with severe pneumonia were randomly allocated to either initial hospitalisation and parenteral ampicillin (100 mg/kg per day in four doses) for 48 h, followed by 3 days of oral amoxicillin (80–90 mg/kg per day; n=1012) or to home-based treatment for 5 days with oral amoxicillin (80–90 mg/kg per day in two doses; n=1025). Follow-up assessments were done at 1, 3, 6, and 14 days after enrolment. The primary outcome was treatment failure (clinical deterioration) by day 6. Analyses were done per protocol and by intention to treat. This trial is registered, ISRCTN95821329. In the per-protocol population, 36 individuals were excluded from the hospitalised group and 37 from the ambulatory group, mainly because of protocol violations or loss to follow-up. There were 87 (8·6%) treatment failures in the hospitalised group and 77 (7·5%) in the ambulatory group (risk difference 1·1%; 95% CI −1·3 to 3·5) by day 6. Five (0·2%) children died within 14 days of enrolment, one in the ambulatory group and four in the hospitalised group. In each case, treatment failure was declared before death and the antibiotic had been changed. None of the deaths were considered to be associated with treatment allocation; there were no serious adverse events reported in the trial. Home treatment with high-dose oral amoxicillin is equivalent to currently recommended hospitalisation and parenteral ampicillin for treatment of severe pneumonia without underlying complications, suggesting that WHO recommendations for treatment of severe pneumonia need to be revised.

Infections remain a leading cause of death in neonates. The sparse antibiotic development pipeline and challenges in conducting neonatal research have resulted in few effective antibiotics being adequately studied to treat multidrug-resistant (MDR) infections in neonates, despite the increasing global mortality burden caused by antimicrobial resistance. Of 40 antibiotics approved for use in adults since 2000, only four have included dosing information for neonates in their labelling. Currently, 43 adult antibiotic clinical trials are recruiting patients, compared with only six trials recruiting neonates. We review the World Health Organization (WHO) priority pathogens list relevant to neonatal sepsis and propose a WHO multiexpert stakeholder meeting to promote the development of a neonatal priority antibiotic development list. The goal is to develop international, interdisciplinary consensus for an accelerated neonatal antibiotic development programme. This programme would enable focused research on identified priority antibiotics for neonates to reduce the excess morbidity and mortality caused by MDR infections in this vulnerable population.