Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis
Open Access
- 22 May 2023
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Medicine
- Vol. 20 (5), e1004239
- https://doi.org/10.1371/journal.pmed.1004239
Abstract
Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs) but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases. We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality—with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 1.49% [CrI: 0.33 to 3.51] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 5% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis. A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.Keywords
Funding Information
- Bill and Melinda Gates Foundation (OPP1190803)
- Princeton University (Smith-Newton Environmental Scholarship)
- Centers for Disease Control and Prevention (21IPA2113462)
- National Science Foundation (CCF1918628)
This publication has 36 references indexed in Scilit:
- Challenges in the diagnosis and management of neonatal sepsisJournal of Tropical Pediatrics, 2015
- Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysisThe Lancet, 2014
- Antibiotic Use and Emerging Resistance: How Can Resource-Limited Countries Turn the Tide?CVD Prevention and Control, 2014
- Estimates of possible severe bacterial infection in neonates in sub-Saharan Africa, south Asia, and Latin America for 2012: a systematic review and meta-analysisThe Lancet Infectious Diseases, 2014
- Tetanus in developing countries: an update on the Maternal and Neonatal Tetanus Elimination InitiativeVaccine, 2003
- Maternal Antibodies, Childhood Infections, and Autoimmune DiseasesThe New England Journal of Medicine, 2001
- Immunogenicity of a 24-Valent Klebsiella Capsular Polysaccharide Vaccine and an Eight-Valent Pseudomonas O-Polysaccharide Conjugate Vaccine Administered to Victims of Acute TraumaClinical Infectious Diseases, 1996
- Phase 1 trial of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered simultaneouslyVaccine, 1994
- The concept of herd immunity and the design of community-based immunization programmesVaccine, 1992
- Large Sample Properties of Simulations Using Latin Hypercube SamplingTechnometrics, 1987