Evolution of pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine.

2022

e0262225

2022

1932-6203

<p>Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.</p>

10.1371/journal.pone.0262225

PLoS One

34986196

Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy.

2021

2021 Sep 11

1751-7370

<p>Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0-6 months of age) or bimonthly (6-12 months of age) from 179 mother-infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.</p>

10.1038/s41396-021-01108-4

ISME J

34511605

Effect of Haemophilus influenzae type b and 13-valent pneumococcal conjugate vaccines on childhood pneumonia hospitalizations and deaths in Botswana.

2020

2020 Jul 08

1537-6591

<p><strong>BACKGROUND: </strong>Globally, pneumonia is the leading cause of death among children. Few data exist regarding the effect of Haemophilus influenzae type b (Hib) vaccine and 13-valent pneumococcal conjugate vaccine (PCV-13) on the burden of childhood pneumonia in African settings.</p>

<p><strong>METHODS: </strong>We collected data on children 1 to 59 months of age at three hospitals in Botswana. Hib vaccine and PCV-13 were introduced in Botswana in November 2010 and July 2012, respectively. We compared pneumonia hospitalizations and deaths pre-vaccine (January 2009 to October 2010) to post-vaccine (January 2013 to December 2017) using seasonally-adjusted interrupted time-series analyses.</p>

<p><strong>FINDINGS: </strong>We identified 6943 pneumonia hospitalizations and 201 pneumonia deaths. In the pre-vaccine period, pneumonia hospitalizations and deaths increased by 24% (rate: 1.24; 95% CI: 0.94, 1.64) and 59% (rate: 1.59; 95% CI: 0.87, 2.90) per year, respectively. Vaccine introduction was associated with a 48% (95% CI: 29%, 62%) decrease in the number of pneumonia hospitalizations and a 50% (95% CI: 1%, 75%) decrease in the number of pneumonia deaths between the end of the pre-vaccine period (October 2010) and the beginning of the post-vaccine period (January 2013). During the post-vaccine period, pneumonia hospitalizations and deaths declined by 6% (rate 0.94; 95% CI: 0.89, 0.99) and 22% (rate: 0.78; 95% CI: 0.67, 0.92) per year, respectively.</p>

<p><strong>INTERPRETATION: </strong>Pneumonia hospitalizations and deaths among children declined sharply following introduction of Hib vaccine and PCV-13 in Botswana. This effect was sustained for more than five years after vaccine introduction, supporting the long-term effectiveness of these vaccines in preventing childhood pneumonia in Botswana.</p>

10.1093/cid/ciaa919

Clin. Infect. Dis.

32634831

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

Predictors of Poor Outcomes among Infants with Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection in Botswana.

2018

2018 Dec 05

1532-0987

<p>Among children one to 23 months of age with respiratory syncytial virus-associated acute lower respiratory infection in Botswana, young age (&lt;6 months), household use of wood as a cooking fuel, moderate or severe malnutrition, and oxygen saturation &lt;90% on room air were independent predictors of clinical non-response at 48 hours. Among HIV-uninfected infants less than six months of age, HIV exposure was associated with a higher risk of in-hospital mortality.</p>

10.1097/INF.0000000000002168

Pediatr. Infect. Dis. J.

30543564