Neonatal infection: a major burden with minimal funding
Authors: Anna C Seale, Michael G Head, Elizabeth J A Fitchett, Stefania Vergnano, Samir K Saha, Paul T Heath, Mike Sharland, Joy E Lawn
Journal: The Lancet Global Health (2015)

Further progress in decreasing child mortality depends on reducing the 2·9 million neonatal deaths each year, around a quarter of which are directly due to infection.1Lawn JE Blencowe H Oza S et al.Every Newborn: progress, priorities, and potential beyond survival.Lancet. 2014; 384: 189-205Summary Full Text Full Text PDF PubMed Scopus (1082) Google Scholar However, systemic underfunding is limiting research and threatens further advances. The need is great: an estimated 6·9 million neonates required treatment for possible serious bacterial infection in 2012 in high-burden settings,2Seale AC Blencowe H Manu AA et al.Estimates of possible severe bacterial infection in neonates in sub-Saharan Africa, south Asia, and Latin America for 2012: a systematic review and meta-analysis.Lancet Infect Dis. 2014; 14: 731-741Summary Full Text Full Text PDF PubMed Scopus (187) Google Scholar and the Global Burden of Disease Study estimates suggest that neonatal infections account for around 3% of disability-adjusted life-years (DALYs), with insufficient data to estimate long-term disability after sepsis or pneumonia.3Murray CJ Vos T Lozano R et al.Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.Lancet. 2013; 380: 2197-2223Summary Full Text Full Text PDF Scopus (6467) Google Scholar, 4Seale AC Blencowe H Zaidi A et al.Neonatal severe bacterial infection impairment estimates in South Asia, sub-Saharan Africa, and Latin America for 2010.Pediatr Res. 2013; 74: 73-85Crossref PubMed Scopus (105) Google Scholar Even with the limitations in the available data on DALYs, the funding gap is huge. The Research Investments in Global Health study5Head MG Fitchett JR Cooke MK Wurie FB Hayward AC Atun R UK investments in global infectious disease research 1997-2010: a case study.Lancet Infect Dis. 2013; 13: 55-64Summary Full Text Full Text PDF PubMed Scopus (61) Google Scholar analysed public and philanthropic infectious disease research awards to UK institutions (1997–2013), and compared them to the burden in DALYs,3Murray CJ Vos T Lozano R et al.Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.Lancet. 2013; 380: 2197-2223Summary Full Text Full Text PDF Scopus (6467) Google Scholar describing a new metric of “investment per DALY observed”. The results are stark: neonatal infectious diseases received the lowest investment of all infections, £0·01 per DALY. By contrast, HIV and malaria had investments of £0·46 and £0·34 per DALY (figure, appendix) and some neglected tropical diseases have strikingly high investments—eg, African trypanosomiasis received £9·06 per DALY. Attracting additional funding and increasing capacity is essential to meet research needs and must be matched with improved scientific reporting; the forthcoming Strengthening Publications Reporting Infections in Newborns Globally (SPRING) standards are an important step towards this goal. However, well funded research in neonatal infection is essential. In health facilities, high quality surveillance data can provide important information on cause6Berkley J Lowe BS Mwangi I et al.Bacteremia among children admitted to a rural hospital in Kenya.N Engl J Med. 2005; 352: 39-47Crossref PubMed Scopus (643) Google Scholar and antimicrobial resistance.7Aiken AM Mturi N Njuguna P et al.Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District Hospital, Kenya: a prospective cohort study.Lancet. 2011; 378: 2021-2027Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar But such data require significant resources, including strengthening laboratory quality control and assurance measures, and use and appropriate interpretation of molecular diagnostics to detect pathogens (including viruses). More population-based data are needed; these are difficult to acquire because most neonatal deaths occur in the first few hours after birth when access to care may be limited. Results of the Aetiology of Neonatal Infections in South Asia (ANISA) study are awaited, and forthcoming work includes the Child Health and Mortality Prevention Surveillance Network funded by the Bill & Melinda Gates Foundation in south Asia and sub-Saharan Africa. Preventing infection depends on improving our understanding of maternal health, including maternal colonisation, as well as vertical transmission (HIV, malaria, other congenital infections, and ascending bacterial infections) and hospital-acquired infections, particularly with multiresistant Gram-negative bacteria. Infection control management is important, and interventions, isolated or as part of care bundles, need detailed, prospective evaluation in outbreak situations, such as those proposed by the International Nosocomial Infection Control Consortium. Improving case management partly depends on improving recognition of danger signs by carers and primary health centres. Clinical algorithms used for diagnosing possible serious bacterial infection could be improved through the use of bedside tests, such as pulse oximetry, as well as point of care tests. Clinical trials have recently examined whether outpatient care can be provided to neonates who are not critically ill and where referral for hospital treatment is not possible.8Tshefu A Lokangaka A et al.African Neonatal Sepsis Trial groupOral 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.Lancet. 2015; 385: 1758-1766Summary Full Text Full Text PDF PubMed Scopus (53) Google Scholar These trials have informed new WHO guidelines.9World Health OrganizationManaging possible serious bacterial infection in young infants when referral is not feasible: guidelines.http://www.who.int/maternal_child_adolescent/documents/bacterial-infection-infants/en/Date: 2015Google Scholar However, further research is needed to determine health-system requirements for implementation, and whether this approach reduces uptake of referral to hospital, which remains the standard of care. There are important bottlenecks in health systems to improving neonatal infection case management,10Simen-Kapeu A Seale A Wall S et al.Treatment of neonatal infections: a multi-country analysis of health system bottlenecks and potential solutions.BMC Pregnancy Childbirth. 2015; 15: S6Crossref PubMed Scopus (24) Google Scholar and overcoming these, with appropriate metrics to track neonatal care coverage, are essential. Future trials need to focus on improving mortality outcomes in newborns with sepsis and defining management strategies in settings of varying levels of antimicrobial resistance. The optimum choice of drug, dose, and duration in settings of high resistance to WHO first-line empirical therapy is completely unknown. A joined-up approach from funders and research institutions is urgently needed to strengthen neonatal infection research. This could be through a formal prioritisation exercise leading to calls for specific research funding to support research on neonatal infection. Developing research capacity worldwide is essential to drive forward measures to reduce deaths11Lozano R Naghavi M Foreman K et al.Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.Lancet. 2012; 380: 2095-2128Summary Full Text Full Text PDF PubMed Scopus (10100) Google Scholar and disability from neonatal infection, and to reduce gross inequities in health. The authors are all researchers in neonatal infection. We declare no other competing interests. This Comment is based on discussions held at a Wellcome Trust funded meeting in June, 2015. Additional SPRING group members who contributed to these discussions: Ramesh Agarwal, Adejumoke I Ayede, Zulfiqar A Bhutta, Robert Black, Kalifa Bojang, Harry Campbell, Simon Cousens, Gary L Darmstadt, Shabir A Madhi, Ajoke Sobanjo-ter Meulen, Neena Modi, Janna Patterson, Shamim Qazi, Stephanie J Schrag, Barbara J Stoll, Steve Wall, Robinson Wammanda, James A Berkley, Susan Elden, Christine E Jones, Kirsty Le Doare, and Neal Russell. We also thank Joseph R Fitchett who is working on the Research Investments in Global Health study. Download .pdf (.25 MB) Help with pdf files Supplementary appendix