Spatial Distribution of Invasive Pneumococcal Serotypes in West Africa: A Retrospective Analysis to Inform Immunization in Persons with Sickle Cell Disease
Authors: Carsillo Thomas , Amegan-Aho Kokou Hefoume , Feller Andrea , McIntosh Avery , Spector Jonathan , Obaro Stephen K. 
Published: October 2019

Abstract
Background: Susceptibility to invasive pneumococcal disease (IPD) is high in children with sickle cell disease (SCD). National guidelines in many countries recommend a combined schedule of 13-valent pneumococcal conjugate vaccine (PCV13) beginning after birth followed by the 23-valent polysaccharide vaccine (PPSV23) beginning at age 2 years. In Africa, where the burden of SCD is greatest, PPSV23 is generally unavailable and not routinely administered to children with SCD. To help inform optimal immunization regimens for children with SCD in West Africa, we sought to determine the prevalence and spatial distribution of IPD in the region. We focused specifically on the 24 combined pneumococcus strains covered by PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and PPSV23 (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F). This analysis also explored the epidemiology of IPD-associated serotypes after the introduction of routine PCV13 immunization in countries in West Africa.
Methods: We conducted a systematic review of published literature between 1990 and January 2017 using BIOSIS Previews, Embase, and Ovid MEDLINE. Inclusion criteria were all investigations that reported estimates of prevalence or incidence and the specific serotype distribution profile of invasive Streptococcus pneumoniae (including bacteremia, meningitis, osteomyelitis, or pneumonia) in children and adults in ECOWAS-defined West Africa: Benin, Burkina Faso, Cape Verde, Cote d'Ivoire, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone, and Togo. The search strategy utilized various combinations of relevant keywords and MeSH headings. Timing of the introduction of routine PCV13 immunization into study countries was determined through WHO national immunization coverage surveillance data. We generated maps of the spatial distribution of pneumococcal serotypes in countries with available data using R (version 3.3.3).
Results: The search yielded 540 unique studies. We excluded 395 papers based on title and abstract. The remaining 145 studies underwent full text review. Twenty papers (representing 20 datasets and 1980 isolates) met inclusion criteria. Gambia had the most datasets (5); no data were available from six countries (Benin, Cape Verde, Cote d'Ivoire, Guinea, Liberia, and Sierra Leone); and at least one dataset was available from each of the remaining 8 countries. The most frequent invasive serotypes reported across countries were 1, 5, 6A, 12F, 14, and 23F; together, these represented 79.7% of all serotypes identified in IPD in children and adults in West Africa. Most (89.2%) of the serotypes identified are included in PCV13. However, serotypes 2 and 12F, which are covered only by PPSV23, represented 3.3% and 4.8% of identified IPD serotypes, respectively, across the 9 countries studied. These serotypes also accounted for up to 10% of isolates found in individual countries. PCV13 was introduced into all countries with datasets analyzed between 2011 and 2015. Only 1 dataset identified in the literature search (Ghana) was obtained after the introduction of routine pneumococcal vaccination, which precluded analysis of the impact of vaccination on temporal trends in serotype incidence.
Conclusions: To our knowledge this is the first attempt to aggregate IPD serotype data across West Africa. While the majority of serotypes identified are included in PCV13, two serotypes exclusive to PPSV23 (2 and 12F) together accounted for 8.1% of the total IPD burden. Moreover, in some countries, the proportion of strains included in PPSV23 and not PCV13 is higher. Immunizing persons with SCD in West Africa with PPSV23 therefore may be warranted to optimize protection from IPD. Furthermore, as PCV13 vaccination coverage increases, it is possible that the epidemiology of IPD may shift to more strains exclusively covered by PPSV23. This analysis is limited by its retrospective nature and the paucity of data available after introduction of routine pneumococcal vaccination. Further work, including dynamic IPD surveillance and disease modeling, is needed to better understand the epidemiology of pneumococcus in West Africa with the aim of keeping vulnerable populations, such as those with SCD, safe from IPD.

Disclosures
No relevant conflicts of interest to declare.