Treatment of infections in young infants in low- and middle-income countries: a systematic review and meta-analysis of frontline health worker diagnosis and antibiotic access

Abstract

Background: Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription?

Methods and findings: We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%-91%) and lower specificity (62%, 95% CI 48%-75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%-88%) and specificity of 69% (95% CI 54%-83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%-34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data.

Conclusions: Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs.

Review registration: PROSPERO International prospective register of systematic reviews (CRD42013004586). Please see later in the article for the Editors' Summary.

Figure 1. Conceptual model of access to antibiotics for newborns with infection.

Figure 2. Search strategy and results for literature review of published and grey literature.

Figure 3. Forest plot of studies of diagnostic accuracy of clinical sign (IMCI) algorithms to detect severe disease/pBI in young infants compared to physician-laboratory diagnosis.

Figure 4. Receiver operating curve of studies of diagnostic accuracy of clinical sign algorithms versus physician-laboratory diagnosis of severe disease/pBI in young infants.

Figure 5. Forest plot of studies of diagnostic accuracy of frontline health worker diagnosis of pBI compared to physician diagnosis.

Figure 6. Receiver operating curve of studies of diagnostic accuracy of frontline health worker diagnosis of pBI compared to physician diagnosis.

Figure 7. Meta-analysis of the logit of the prevalence of non-prescription over-the-counter antibiotic use by young infants and children in low- and middle-income countries.

Effect size is the Logit (prevalence of antibiotic purchases that were obtained over the counter without a prescription).