The aetiology of diarrhoea, pneumonia and respiratory colonization of HIV-exposed infants randomized to breast- or formula-feeding.

BACKGROUND: Diarrhoea and pneumonia are common causes of childhood death in sub-Saharan Africa but there are few studies describing specific pathogens. OBJECTIVES: The study aimed to describe the pathogens associated with diarrhoea, pneumonia and oropharyngeal colonization in children born to HIV-infected women (HIV-exposed infants). METHODS: The Mashi Study randomized 1200 HIV-infected women and their infants to breastfeed for 6 months with ZDV prophylaxis or formula-feed with 4 weeks of ZDV. Children were tested for HIV by PCR at 1, 4, 7, 9 and 12 months and by ELISA at 18 months. Pre-defined subsets of children were sampled during episodes of diarrhoea (n = 300) and pneumonia (n = 85). Stool was tested for bacterial pathogens, rotavirus and parasites. Children with pneumonia underwent bacterial blood culture, and testing of nasopharyngeal aspirates for viral pathogens by PCR. Oropharyngeal swabs were collected from a consecutive subset of 561 infants at the routine 3-month visit for bacterial culture. RESULTS: The median age (range) at sampling was 181 days for diarrhoea (0-730) and 140 days for pneumonia (2-551). Pathogens were identified in 55 (18%) children with diarrhoea and 32 (38%) with pneumonia. No differences in pathogens by child HIV status (HIV-infected vs HIV-uninfected) or feeding strategy were identified. Campylobacter was the most common diarrhoeal pathogen (7%). Adenovirus (22%) and other viruses (19%) were the primary pathogens isolated during pneumonias. More formula-fed infants had oropharyngeal colonization by pathogenic Gram-negative bacteria (16.8% vs 6.2%, P = 0.003), which was associated with a non-significant increased risk of pneumonia (OR 2.2, 95% CI 0.8-5.7). CONCLUSION: A trend toward oropharyngeal bacterial colonization was observed in formula-fed infants. Although viruses were most commonly detected during pneumonia, respiratory colonization by Gram-negative bacteria may have contributed to pneumonia in formula-fed infants.

Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges.

INTRODUCTION: The use of antiretroviral therapy (ART) in pregnancy to prevent vertical HIV transmission has been one of the most successful public health programs in the last decade. As a result, an unprecedented number of women are taking ART at conception and during pregnancy. Given few randomized studies evaluating safety of different ART regimens in pregnancy, ongoing drug safety surveillance is critical. Areas covered: This review aims to provide a rationale for ART drug safety surveillance, describe changing patterns of ART use and summarize current surveillance efforts in both low-resource and high-resource settings. Additionally, biostatistical approaches to and challenges in analysis of observational surveillance data are discussed. Expert opinion: The global landscape of ART use in pregnancy is rapidly increasing and evolving. Any increase in adverse effects of in-utero exposure to ART has the potential to reduce the impact of improvements in infant morbidity and mortality gained from decreased vertical HIV transmission. ART drug safety surveillance should therefore be a critical piece of programs to prevent mother to child transmission in both high- and low-resource settings. Current surveillance efforts could be strengthened with long-term follow-up of exposed children, pooling of data across cohorts and standardized approaches to analysis.

Risk factors for mortality among human immunodeficiency virus-exposed and unexposed infants admitted to a neonatal intensive care unit in Botswana.

AIM: Newborns admitted to neonatal units (NNUs) in resource-limited settings face a high risk of mortality, but the epidemiology of these deaths is poorly understood. We describe risk factors for NNU mortality in an area with high prevalence of human immunodeficiency virus (HIV). METHODS: We performed a prospective cohort study of infants admitted to the NNU at a public referral hospital in Gaborone, Botswana. The primary outcome was neonatal death, defined as death within 28 days of a live delivery. Cox proportional hazard models were used to evaluate risk factors for mortality. RESULTS: From October 2008 to April 2009, 449 neonates were admitted to the NNU. Cumulative mortality was 24.5% (110/449). Factors associated with increased risk of death included lack of enteral feeding (hazard ratio (HR) 18.8, 95% confidence interval (CI) 10.3, 34.2), gestational age <28 weeks (HR 2.0, 95% CI 1.1, 3.8) and Apgar score <7 at 10 min (HR 2.5, 95% CI 1.5, 4.2). Among 348 (78%) infants who were fed, there was no difference in mortality between infants who were breastfed compared with those who were formula fed or had mixed feeding (P = 0.76). There was no significant mortality difference by HIV exposure status; 35 (28%) of 128 HIV-exposed infants died compared with 55 (21%) of 272 HIV-unexposed infants (P = 0.19). CONCLUSIONS: This study identified low Apgar scores, extreme prematurity and lack of enteral feeding as the most important risk factors for mortality in this NNU setting. HIV exposure and formula feeding were not significantly associated with death in neonates who were very ill.