Investigating Mediators of the Poor Pneumonia Outcomes of Human Immunodeficiency Virus-Exposed but Uninfected Children.

2017

2017 Nov 20

2048-7207

<p><strong>Background: </strong>Human immunodeficiency virus-exposed but uninfected (HIV-EU) children have a higher mortality rate than the children of HIV-negative mothers (HIV-unexposed). Causal mediators of the poor health outcomes of HIV-EU children remain poorly defined.</p>

<p><strong>Methods: </strong>We conducted a hospital-based prospective cohort study of children aged 1 to 23 months with clinically defined pneumonia. The children were recruited at a referral hospital in Gaborone, Botswana, between April 2012 and June 2016. The primary outcome, treatment failure at 48 hours, was assessed by an investigator blinded to the children's HIV-exposure status. We examined associations between HIV exposure and pneumonia outcomes in HIV-uninfected children. We next determined whether the effect of HIV exposure on outcomes was mediated by low-birth-weight status, nonbreastfeeding, malnutrition, in utero exposure to combination antiretroviral therapy, or pneumonia severity.</p>

<p><strong>Results: </strong>A total of 352 HIV-uninfected children were included in these analyses, including 245 (70%) HIV-unexposed and 107 (30%) HIV-EU children. Their median age was 7.4 months, and 57% were male. Treatment failure occurred in 111 (32%) children, and 19 (5.4%) children died. HIV-EU children were more likely to fail treatment (risk ratio [RR], 1.57 [95% confidence interval (CI), 1.19-2.07]; P = .002) and had a higher in-hospital mortality rate (RR, 4.50 [95% CI, 1.86-10.85]; P = .001) than HIV-unexposed children. Nonbreastfeeding mediated 47% of the effect of HIV exposure on the risk of in-hospital death.</p>

<p><strong>Conclusions: </strong>HIV-EU children have worse pneumonia outcomes than HIV-unexposed children. Nonbreastfeeding mediates nearly half of the effect of HIV exposure on pneumonia mortality. Our findings provide additional evidence for a mortality benefit of breastfeeding by HIV-EU children.</p>

10.1093/jpids/pix092

J Pediatric Infect Dis Soc

29165579

The Nasopharyngeal Microbiota of Children with Respiratory Infections in Botswana.

2017

2017 Apr 10

1532-0987

<p><strong>BACKGROUND: </strong>Nearly half of child pneumonia deaths occur in sub-Saharan Africa. Microbial communities in the nasopharynx are a reservoir for pneumonia pathogens and remain poorly described in African children.</p>

<p><strong>METHODS: </strong>Nasopharyngeal swabs were collected from children with pneumonia (N=204), children with upper respiratory infection symptoms (N=55), and healthy children (N=60) in Botswana between April 2012 and April 2014. We sequenced the V3 region of the bacterial 16S ribosomal RNA gene and used partitioning around medoids to cluster samples into microbiota biotypes. We then used multivariable logistic regression to examine whether microbiota biotypes were associated with pneumonia and upper respiratory infection symptoms.</p>

<p><strong>RESULTS: </strong>Mean ages of children with pneumonia, children with upper respiratory infection symptoms, and healthy children were 8.2, 11.4, and 8.0 months, respectively. Clustering of nasopharyngeal microbiota identified five distinct biotypes: Corynebacterium/Dolosigranulum-dominant (23%), Haemophilus-dominant (11%), Moraxella-dominant (24%), Staphylococcus-dominant (13%), and Streptococcus-dominant (28%). The Haemophilus-dominant [odds ratio (OR): 13.55, 95% confidence interval (CI): 2.10-87.26], the Staphylococcus-dominant (OR: 8.27, 95% CI: 2.13-32.14), and the Streptococcus-dominant (OR: 39.97, 95% CI: 6.63-241.00) biotypes were associated with pneumonia. The Moraxella-dominant (OR: 3.71, 95% CI: 1.09-12.64) and Streptococcus-dominant (OR: 12.26, 95% CI: 1.81-83.06) biotypes were associated with upper respiratory infection symptoms. In children with pneumonia, HIV infection was associated with a lower relative abundance of Dolosigranulum (P=0.03).</p>

<p><strong>CONCLUSIONS: </strong>Pneumonia and upper respiratory infection symptoms are associated with distinct nasopharyngeal microbiota biotypes in African children. A lower abundance of the commensal genus Dolosigranulum may contribute to the higher pneumonia risk of HIV-infected children.</p>

10.1097/INF.0000000000001607

Pediatr. Infect. Dis. J.

28399056