Optimising the management of childhood acute diarrhoeal disease using a rapid test-and- treat strategy and/or Lactobacillus reuteri DSM 17938: a multicentre, randomised, controlled, factorial trial in Botswana.

2022

2022 Apr

2059-7908

<p><strong>INTRODUCTION: </strong>The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy ('test-and-treat') and/or&nbsp;<em>Lactobacillus reuteri</em> DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis.</p>

<p><strong>METHODS: </strong>This was a multicentre, randomised, factorial, controlled, trial. Children aged 2-60 months admitted for acute non-bloody diarrhoea to four hospitals in southern Botswana were eligible. Participants were assigned to treatment groups by web-based block randomisation. Test-and-treat results were not blinded, but participants and research staff were blinded to <em>L. reuteri</em>/placebo assignment; this was dosed as 1×10⁸ cfu/mL by mouth daily and continued for 60 days. The primary outcome was 60-day age-standardised height (HAZ) adjusted for baseline HAZ. All analyses were by intention to treat. The trial was registered at Clinicaltrials.gov.</p>

<p><strong>RESULTS: </strong>Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus <em>L. reuteri&nbsp;</em>group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus <em>L. reuteri&nbsp;</em>group and 69 to the standard care plus placebo group. There was no demonstrable impact of the test-and-treat intervention (mean increase of 0.01 SD, 95% CI -0.14 to 0.16 SD) or the&nbsp;<em>L. reuteri</em> intervention (mean decrease of 0.07 SD, 95% CI -0.22 to 0.08 SD) on adjusted HAZ at 60 days.</p>

<p><strong>CONCLUSIONS: </strong>In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of <em>L. reuteri&nbsp;</em>DSM 17938, were found to markedly impact linear growth or other important outcomes. We cannot exclude the possibility that test-and-treat will improve the care of children with significant enteropathogens (such as <em>Shigella</em>) in their stool.</p>

<p><strong>TRIAL REGISTRATION NUMBER: </strong>NCT02803827.</p>

10.1136/bmjgh-2021-007826

BMJ Glob Health

35418412

Placental Transfer of Respiratory Syncytial Virus Antibody Among HIV-Exposed, Uninfected Infants.

2019

2019 Sep 24

2048-7207

<p><strong>BACKGROUND: </strong>Maternal human immunodeficiency virus (HIV) infection is associated with lower placental transfer of antibodies specific to several childhood pathogens. Our objective for this study was to evaluate the effect of maternal HIV infection on the placental transfer of respiratory syncytial virus (RSV)-neutralizing antibodies.</p>

<p><strong>METHODS: </strong>We conducted a cross-sectional study of mothers and their newborn infants at a tertiary hospital in Gaborone, Botswana, between March 2015 and December 2015. We measured serum RSV antibody levels by using a microneutralization assay. We used multivariable linear regression to evaluate the effect of maternal HIV infection on maternal RSV antibody levels, placental transfer of RSV antibodies, and newborn RSV antibody levels.</p>

<p><strong>RESULTS: </strong>Of 316 mothers, 154 (49%) were infected with HIV. The placental transfer ratios for RSV antibodies to HIV-exposed, uninfected (HEU) and HIV-unexposed, uninfected infants were 1.02 and 1.15, respectively. The geometric mean titer (95% confidence interval) of RSV-neutralizing antibodies was 2657 (2251-3136) among HEU newborns and 2911 (2543-3331) among HIV-unexposed, uninfected newborns. In multivariable analyses, maternal HIV infection was associated with lower placental transfer of RSV antibodies (P = .02) and a lower level of RSV antibodies among newborns (P = .002). Among HEU newborns, higher birth weight (P = .004) and an undetectable maternal antenatal viral load (P = .01) were associated with more effective placental transfer of RSV antibodies.</p>

<p><strong>CONCLUSIONS: </strong>Maternal human immunodeficiency virus (HIV) infection is associated with lower mother-to-fetus transfer of serum RSV-neutralizing antibodies. HEU infants should be prioritized for preventive interventions for RSV. Maternal viral suppression through combination antiretroviral therapy has the potential to improve immunity to RSV among HIV-exposed infants.</p>

10.1093/jpids/piz056

J Pediatric Infect Dis Soc

31549157

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