A multi-country implementation research initiative to jump-start scale-up of outpatient management of possible serious bacterial infections (PSBI) when a referral is not feasible: Summary findings and implications for programs.

Introduction: 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.

How is implementation research applied to advance health in low-income and middle-income countries?

This paper examines the characteristics of implementation research (IR) efforts in low-income and middle-income countries (LMICs) by describing how key IR principles and concepts have been used in published health research in LMICs between 1998 and 2016, with focus on how to better apply these principles and concepts to support large-scale impact of health interventions in LMICs. There is a stark discrepancy between principles of IR and what has been published. Most IR studies have been conducted under conditions where the researchers have considerable influence over implementation and with extra resources, rather than in 'real world' conditions.

Impact of integrating a postpartum family planning program into a community-based maternal and newborn health program on birth spacing and preterm birth in rural Bangladesh.

Background: Short birth intervals are associated with an increased risk of adverse perinatal outcomes. However, reduction of rates of short birth intervals is challenging in low-resource settings where majority of the women deliver at home with limited access to family planning services immediately after delivery. This study examines the feasibility of integrating a post-partum family planning intervention package within a community-based maternal and newborn health intervention package, and evaluates the impact of integration on reduction of rates of short birth intervals and preterm births.

Methodology for a mixed-methods multi-country study to assess recognition of and response to maternal and newborn illness.

Background: Although maternal and newborn mortality have decreased 44 and 46% respectively between 1990 and 2015, achievement of ambitious Sustainable Development Goal targets requires accelerated progress. Mortality reduction requires a renewed focus on the continuum of maternal and newborn care from the household to the health facility. Although barriers to accessing skilled care are documented for specific contexts, there is a lack of systematic evidence on how women and families identify maternal and newborn illness and make decisions and subsequent care-seeking patterns.

Perspectives from NHLBI Global Health Think Tank Meeting for Late Stage (T4) Translation Research.

Almost three-quarters (74%) of all the noncommunicable disease burden is found within low- and middle-income countries. In September 2014, the National Heart, Lung, and Blood Institute held a Global Health Think Tank meeting to obtain expert advice and recommendations for addressing compelling scientific questions for late stage (T4) research-research that studies implementation strategies for proven effective interventions-to inform and guide the National Heart, Lung, and Blood Institute's global health research and training efforts. Major themes emerged in two broad categories: 1) developing research capacity; and 2) efficiently defining compelling scientific questions within the local context.

iCCM policy analysis: strategic contributions to understanding its character, design and scale up in sub-Saharan Africa.

Pneumonia, diarrhoea and malaria remain leading causes of death for children under 5 years of age and access to effective and appropriate treatment for sick children is extremely low where it is needed most. Integrated community case management (iCCM) enables community health workers to provide basic lifesaving treatment for sick children living in remote communities for these diseases. While many governments in sub-Saharan Africa recently changed policies to support iCCM, large variations in implementation remain.

Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial.

Background: Severe infections remain one of the main causes of neonatal deaths worldwide. Possible severe infection is diagnosed in young infants (aged 0-59 days) according to the presence of one or more clinical signs. The recommended treatment is hospital admission with 7-10 days of injectable antibiotic therapy.

Financial incentives and maternal health: where do we go from here?

Health financing strategies that incorporate financial incentives are being applied in many low- and middle-income countries, and improving maternal and neonatal health is often a central goal. As yet, there have been few reviews of such programmes and their impact on maternal health. The US Government Evidence Summit on Enhancing Provision and use of Maternal Health Services through Financial Incentives was convened on 24-25 April 2012 to address this gap.

Scientific rationale for study design of community-based simplified antibiotic therapy trials in newborns and young infants with clinically diagnosed severe infections or fast breathing in South Asia and sub-Saharan Africa.

Background: Newborns and young infants suffer high rates of infections in South Asia and sub-Saharan Africa. Timely access to appropriate antibiotic therapy is essential for reducing mortality. In an effort to develop community case management guidelines for young infants, 0-59 days old, with clinically diagnosed severe infections, or with fast breathing, 4 trials of simplified antibiotic therapy delivered in primary care clinics (Pakistan, Democratic Republic of Congo, Kenya and Nigeria) or at home (Bangladesh and Nigeria) are being conducted.

Ongoing trials of simplified antibiotic regimens for the treatment of serious infections in young infants in South Asia and sub-Saharan Africa: implications for policy.

Background: The current World Health Organization (WHO) recommendation for treatment of severe infection in young infants is hospitalization and parenteral antibiotic therapy. Hospital care is generally not available outside large cities in low- and middle-income countries and even when available is not acceptable or affordable for many families. Previous research in Bangladesh and India demonstrated that treatment outside hospitals may be possible.

Ensuring quality in AFRINEST and SATT: clinical standardization and monitoring.

Background: Three randomized open-label clinical trials [Simplified Antibiotic Therapy Trial (SATT) Bangladesh, SATT Pakistan and African Neonatal Sepsis Trial (AFRINEST)] were developed to test the equivalence of simplified antibiotic regimens compared with the standard regimen of 7 days of parenteral antibiotics. These trials were originally conceived and designed separately; subsequently, significant efforts were made to develop and implement a common protocol and approach. Previous articles in this supplement briefly describe the specific quality control methods used in the individual trials; this article presents additional information about the systematic approaches used to minimize threats to validity and ensure quality across the trials.

Safety and efficacy of simplified antibiotic regimens for outpatient treatment of serious infection in neonates and young infants 0-59 days of age in Bangladesh: design of a randomized controlled trial.

Background: Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7-10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections.

Methods: We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. The reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days.

An innovative multipartner research program to address detection, assessment and treatment of neonatal infections in low-resource settings.

Background: In pursuit of innovative approaches for the management of severe infections in young infants, which is a major cause of mortality, a multipartner research program was conceptualized to provide right care in the right place. The primary objective was to generate evidence and identify a simple, safe and effective treatment regimen for young infants with severe infections that can be provided closer to home by trained health workers where referral is not possible.

Research: Published and nonpublished data on community-based approaches for the management of neonatal sepsis were critically reviewed by an independent expert panel convened in 2007 by the World Health Organization in collaboration with the United States Agency for International Development and Save the Children/Saving Newborn Lives.