Serotype Profile of Nasopharyngeal Isolates of Streptococcus pneumoniae Obtained from Children in Burkina Faso before and after Mass Administration of Azithromycin

Abstract

Mass drug administration (MDA) with azithromycin (AZ) has been used successfully to control trachoma. However, several studies have shown that MDA with AZ has led to the emergence of resistance to AZ in Streptococcus pneumoniae. The emergence of resistance to AZ has also been observed when this antibiotic was combined with the antimalarials used for seasonal malaria chemoprevention (SMC). The development of antibiotic resistance, including resistance to AZ, is sometimes associated with the emergence of a bacterial clone that belongs to a specific serotype. We hypothesize that the increase in resistance of S. pneumoniae observed after 3 years of SMC with AZ might be associated with a change in the distribution of pneumococcal serotypes. Therefore, 698 randomly selected isolates from among the 1,468 isolates of S. pneumoniae obtained during carriage studies undertaken during an SMC plus AZ trial were serotyped. A polymerase chain reaction (PCR) multiplex assay using an algorithm adapted to the detection of the pneumococcal serotypes most prevalent in African countries was used for initial serotyping, and the Quellung technique was used to complement the PCR technique when necessary. Fifty-six serotypes were detected among the 698 isolates of S. pneumoniae. A swift appearance and disappearance of many serotypes was observed, but some serotypes including 6A, 19F, 19A, 23F, and 35B were persistent. The distribution of serotypes between isolates obtained from children who had received AZ or placebo was similar. An increase in AZ resistance was seen in several serotypes following exposure to AZ. Mass drug administration with AZ led to the emergence of resistance in pneumococci of several different serotypes and did not appear to be linked to the emergence of a single serotype.

Figure 1.

Flowchart for the study of the effect of azithromycin administration on nasopharyngeal serotype of Streptococcus pneumoniae, Burkina Faso, 2014–2016. Numbers in the lowest row of the boxes show the numbers of isolates that were serotyped at each survey.

Figure 2.

Distribution of nasopharyngeal pneumococcal serotypes before and after azithromycin administration in 2014. The proportions of serotypes detected at the respective study visit are shown: orange bars represent azithromycin-susceptible isolates, and blue bars represent azithromycin-resistant isolates. Pneumococcal conjugate vaccination 13 vaccine-type (VT) serotypes are grouped at the bottom of the figure. This figure appears in color at www.ajtmh.org.

Figure 3.

Distribution of nasopharyngeal pneumococcal serotypes before and after azithromycin administration in 2015. The proportions of serotypes detected at the respective study visit are shown: orange bars represent azithromycin-susceptible isolates, and blue bars represent azithromycin-resistant isolates. Pneumococcal conjugate vaccination 13 vaccine-type (VT) serotypes are grouped at the bottom of the figure. This figure appears in color at www.ajtmh.org.

Figure 4.

Distribution of nasopharyngeal pneumococcal serotypes before and after azithromycin administration in 2016. The proportions of serotypes detected at the respective study visit are shown: orange bars represent azithromycin-susceptible isolates, and blue bars represent azithromycin-resistant isolates. Pneumococcal conjugate vaccination 13 vaccine-type (VT) serotypes are grouped at the bottom of the figure. This figure appears in color at www.ajtmh.org.

Figure 5.

Prevalence of pneumococcal isolates that were of vaccine serotype by treatment arm during the course of the trial.