Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

Maria Garcia Quesada,Marcela Guevara,Ron Dagan,Idrissa Diawara,Stefanie Desmet,Yangyupei Yang,Shamez Ladhani,Mark Van Der Linden,Sanjay Jayasinghe,Ryan Gierke,Romina Camilli,Jackie Kleynhans,Lena Setchanova,Naor Bar-Zeev,Markus Hilty,Jonathan Zintgraff,Emmanuelle Varon,Krow Ampofo,Allison Mcgeer,Philippe De Wals,Grettel Chanto Chacón,Kyla Hayford,Kazunori Oishi,Andrew Smith,Cheryl Cohen,Larisa Savrasova,Mary Corcoran,Pak-Leung Ho,Michelle Ang,J Pekka Nuorti ,Karl G Kristinsson ,Meagan E Peterson ,Samanta Cristine Grassi Almeida ,Adam L Cohen ,Leah J Ricketson ,Marı́a Teresa Valenzuela ,İnci Yıldırım ,Scott L Zeger ,Brita Askeland Winje ,Daniel R Feikin ,Juan Carlos Sanz ,Laura L Hammitt ,Michael G Bruce ,Palle Valentiner‐Branth ,Julia C Bennett ,Jason M Mwenda ,Nina M Van Sorge ,Pilar Ciruela Navas ,Maria Deloria Knoll

doi:10.3390/microorganisms9040738

Abstract

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5–7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.

Highlights

Pneumococcal meningitis is a major cause of childhood morbidity and mortality globally, estimated to have caused 83,900 cases and 37,900 deaths in 2015 [1]
Of the 76 sites with invasive pneumococcal disease (IPD) data eligible for data collection and that participated in the PSERENADE project, 32 PCV13-using sites and eight PCV10-using sites had serotypespecific pneumococcal meningitis cases in the mature PCV10/13 period eligible for this analysis
We found that in settings where PCV10 or PCV13 have been used for about seven years with primary series uptake above 70%, the percentage of remaining pneumococcal meningitis due to serotypes covered by the vaccines in use was low: 5.3% in PCV10 sites and 14.1% in PCV13 sites in children

Summary

Introduction

Pneumococcal meningitis is a major cause of childhood morbidity and mortality globally, estimated to have caused 83,900 cases and 37,900 deaths in 2015 [1]. Meningitis is estimated to make up approximately 2% of all severe pneumococcal disease and 12% of pneumococcal deaths [1]. Prior to the introduction of pneumococcal conjugate vaccines (PCV) into routine childhood immunization programs, over 70% of invasive pneumococcal disease (IPD), a serious form of pneumococcal disease that includes bacteremic pneumonia, meningitis, and sepsis, was estimated to have been caused by serotypes targeted by the vaccines currently available [2]. PCVs currently in wide use include a 10valent vaccine (PCV10; GlaxoSmithKline (GSK), Synflorix) and a 13-valent vaccine (PCV13; Pfizer, Prevnar13/Prevenar). PCVs currently in wide use include a 10valent vaccine (PCV10; GlaxoSmithKline (GSK), Synflorix) and a 13-valent vaccine (PCV13; Pfizer, Prevnar13/Prevenar13) Another 10-valent vaccine (Serum Institute of India (SII), Pneumosil) became available in 2019. The 23-valent pneumococcal polysaccharide vaccine (PPV23; Merck, Pneumovax23) is recommended in many countries for older adults and those at high risk for pneumococcal disease but is not widely used [8]

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