Clinically diagnosed neonatal sepsis ranged from 49 per 1000 live births in babies older than 24 hours of life in rural Guatemala,47 to as high as 170 per 1000 live births detected by village health workers in rural India.51,56 A first-level facility in Kenya estimated a minimal rate of blood culture confirmed sepsis of 5.5 per 1000 live births among neonates presenting to this facility.57 In the absence of active household surveillance, however, the true incidence is expected to be significantly higher.
The studies reviewed and data presented are limited by substantial inter- and intracountry variation, methodological heterogeneity in population selection and completeness of follow-up, as well as possible misclassifications and/or biases in cause of death ascertainment. The main reason for such inaccuracies includes lack of vital registration or surveillance systems in developing countries, where the majority of babies are born, and succumb to infections, within their homes–seldom, if ever, coming to medical attention.2,59 Other reasons compounding uncertainty include lack of standardization as well as inherent limitations of verbal autopsy tools, comorbid, and often multiple causes of neonatal death.40,42,46,59–62 Sparse data from regions of the world, such as Sub-Saharan Africa, where the highest burden of childhood illness lies, also limits the generalizability of these data.61
Accurate information on causes of death is crucial to designing intervention programs and monitoring progress and sustainability of interventions as well as providing data for intracountry and regional comparisons.1,62
Despite the glaring limitations in the quality and quantity of data discussed above, studies consistently implicate infections as a major cause of neonatal morbidity and mortality in the developing world. Evidence-based strategies for prevention and management of newborn infections in low-income countries are thus urgently needed.
Current WHO recommendations for treating serious bacterial infections in infants under 2 months of age include hospitalization and 10 days of parenteral therapy.63–66 However, these recommendations are inadequately followed in developing countries with high burden of neonatal deaths–due to logistic and resource constraints–and socio-cultural factors such as confinement after birth, unwillingness of families to seek care outside the home, and frequent rejection or refusal of allopathic or facility-based care.35,47,51,67–69 Moreover, because of delays in care seeking, inadequate or poor quality care, unhygienic handling and feeding, contaminated hospital equipment, and multiresistant hospital-acquired pathogens, case fatality rates for sepsis among hospitalized babies treated with recommended therapy are as high as 30% to 50%.4,6,70 These findings suggest that alternate approaches for prevention, early detection, and management of neonatal infections, such as those implemented within the community or home, may have a greater impact in reducing neonatal mortality in the near-term.
There is continued need for development and validation of simplified diagnostic algorithms, in addition to development of evidence-based treatment guidelines, to enable minimally trained health care workers to effectively manage neonatal sepsis during home-visits, or at first level facilities.77 In addition to research addressing numerous health system challenges and constraints for implementation and sustainability, an exploration of etiological agents, drug resistance patterns, and antibiotic regimens is required before community-based case management strategies utilizing antibiotics can be employed on national scales in developing countries with high burden of neonatal mortality.
These issues are discussed further in related articles in this supplement, which aims to (1) describe the pathogens causing serious bacterial infections among neonatal and young infants in developing country community settings; (2) antimicrobial resistance patterns of major etiological agents causing these infections; (3) treatment options for management of these infections in community settings, including a pharmacological appraisal of potential antimicrobials; and (4) identify research gaps and future directions.
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