Pneumococcal carriage and serotype distribution among children with and without pneumonia in Mozambique, 2014-2016

<div><p>Background</p><p>Pneumococcal colonization is a precursor to pneumonia, and pneumococcal conjugate vaccines (PCV) can decrease vaccine-type (VT) colonization. Pneumococcal colonization studies are traditionally done among healthy children in the community; however, VT colonization prevalence may differ between these children and those with pneumonia. We assessed overall and VT pneumococcal colonization and factors associated with colonization among children with and without pneumonia after Mozambique introduced 10-valent PCV (PCV10) in 2013.</p><p>Methods</p><p>We used data from ongoing pneumonia surveillance in children aged <5 years and from cross-sectional nasopharyngeal colonization surveys conducted in October 2014 –April 2015 and October 2015 –May 2016. Pneumonia was defined using WHO standard criteria for radiologically confirmed pneumonia. Children with pneumonia enrolled from January 2014 –April 2016 were compared to children without pneumonia enrolled from the cross-sectional surveys. Clinical data and nasopharyngeal (NP) swabs were collected from each child. NP specimens were cultured for pneumococci, and culture-negative specimens from children with pneumonia underwent polymerase chain reaction (PCR).</p><p>Results</p><p>Of 778 and 927 children with and without pneumonia, 97.4% and 27.0% were exposed to antibiotics before swab collection, respectively. Based on culture, pneumococcal colonization was 45.1% for children with and 84.5% for children without pneumonia (<i>P</i><0.001); VT pneumococcal colonization was 18.6% for children with and 23.4% for children without pneumonia (<i>P</i> = 0.02). The addition of PCR in children with pneumonia increased overall and VT-pneumococcal colonization to 79.2% and 31.1%, respectively. In multivariable analysis including PCR results, pneumonia was associated with VT pneumococcal colonization (adjusted OR: 1.4, 95%CI: 1.10–1.78).</p><p>Conclusion</p><p>Vaccine-type pneumococcal colonization remains common among children with and without pneumonia post-PCV10 introduction in Mozambique. In a population of children with high antibiotic exposure, the use of PCR for culture-negative NP swabs can improve assessment of pneumococcal colonization and circulating serotypes.</p></div

Characteristics of children aged <5 years with and without pneumonia in Manhiça and Maputo, Mozambique, 2014–2016.

<p>Characteristics of children aged <5 years with and without pneumonia in Manhiça and Maputo, Mozambique, 2014–2016.</p

Distribution of serotypes among children aged < 5 years with pneumococcal colonization in Manhiça and Maputo, Mozambique, 2014–2016.

<p>Distribution of serotypes among children aged < 5 years with pneumococcal colonization in Manhiça and Maputo, Mozambique, 2014–2016.</p

Factors associated with overall pneumococcal colonization in children aged < 5 years in Manhiça and Maputo, Mozambique, 2014–2016.

<p>Factors associated with overall pneumococcal colonization in children aged < 5 years in Manhiça and Maputo, Mozambique, 2014–2016.</p

Factors associated with vaccine-type^a pneumococcal colonization in children aged < 5 years in Manhiça and Maputo, Mozambique, 2014–2016.

<p>Factors associated with vaccine-type<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199363#t003fn001" target="_blank">^a</a> pneumococcal colonization in children aged < 5 years in Manhiça and Maputo, Mozambique, 2014–2016.</p

Prevalence of pneumococcal carriage by HIV infection, HIV exposure, and site.

<p>Prevalence of pneumococcal carriage by HIV infection, HIV exposure, and site.</p

Nasopharyngeal carriage of <i>Streptococcus pneumoniae</i> among HIV-infected and –uninfected children <5 years of age before introduction of pneumococcal conjugate vaccine in Mozambique

<div><p>Nasopharyngeal carriage is a precursor for pneumococcal disease and can be useful for evaluating pneumococcal conjugate vaccine (PCV) impact. We studied pre-PCV pneumococcal carriage among HIV-infected and -uninfected children in Mozambique. Between October 2012 and March 2013, we enrolled HIV-infected children age <5 years presenting for routine care at seven HIV clinics in 3 sites, including Maputo (urban-south), Nampula (urban-north), and Manhiça (rural-south). We also enrolled a random sample of HIV-uninfected children <5 years old from a demographic surveillance site in Manhiça. A single nasopharyngeal swab was obtained and cultured following enrichment in Todd Hewitt broth with yeast extract and rabbit serum. Pneumococcal isolates were serotyped by Quellung reaction and multiplex polymerase chain reaction. Factors associated with pneumococcal carriage were examined using logistic regression. Overall pneumococcal carriage prevalence was 80.5% (585/727), with similar prevalences among HIV-infected (81.5%, 339/416) and HIV-uninfected (79.1%, 246/311) children, and across age strata. Among HIV-infected, after adjusting for recent antibiotic use and hospitalization, there was no significant association between study site and colonization: Maputo (74.8%, 92/123), Nampula (83.7%, 82/98), Manhiça (84.6%, 165/195). Among HIV-uninfected, report of having been born to an HIV-infected mother was not associated with colonization. Among 601 pneumococcal isolates from 585 children, serotypes 19F (13.5%), 23F (13.1%), 6A (9.2%), 6B (6.2%) and 19A (5.2%) were most common. The proportion of serotypes included in the 10- and 13-valent vaccines was 44.9% and 61.7%, respectively, with no significant differences by HIV status or age group. Overall 36.9% (n = 268) of children were colonized with a PCV10 serotype and 49.7% (n = 361) with a PCV13 serotype. Pneumococcal carriage was common, with little variation by geographic region, age, or HIV status. PCV10 was introduced in April 2013; ongoing carriage studies will examine the benefits of PCV10 among HIV-infected and–uninfected children.</p></div

Factors associated with pneumococcal colonization among HIV-infected and–uninfected children aged <5 years in Mozambique.

<p>Factors associated with pneumococcal colonization among HIV-infected and–uninfected children aged <5 years in Mozambique.</p

Serotype distribution among nasopharyngeal <i>Streptococcus pneumoniae</i> isolates (n = 601) found among HIV-infected and -uninfected children aged <5 years in Mozambique.

<p>Serotype distribution among nasopharyngeal <i>Streptococcus pneumoniae</i> isolates (n = 601) found among HIV-infected and -uninfected children aged <5 years in Mozambique.</p

Rate ratio of PCV10 dosing schedule according to pneumococccal vaccine-type nasopharyngeal carriage.

§<p>Administered only for previously unvaccinated children who received the vaccine at 12 months of age or older.</p>†<p>Includes non-vaccine type carriage and non-carriage children.</p>‡<p>34 isolates missing Quellung reaction results: unvaccinated (n = 9), one catch-up dose (n = 8), 2p+0 (n = 6), 3p+0 (n = 11).</p