Distribution of capsule and O types in Klebsiella pneumoniae causing neonatal sepsis in Africa and South Asia : A meta-analysis of genome-predicted serotype prevalence to inform potential vaccine coverage

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Stanton, Thomas D. and Keegan, Shaun P. and Abdulahi, Jabir A. and Amulele, Anne V. and Bates, Matthew and Heinz, Eva and Hooda, Yogesh and Hu, Weiming and Jain, Kajal and Kanwar, Samiah and Magobo, Rindidzani and Olwagen, Courtney P. and Tembo, John M. and Sonda, Tolbert and Strysko, Jonathan and Tigoi, Caroline C. and Amin, Sameen Ahmad and Bittinger, Kyle and Cornick, Jennifer and Foster-Nyarko, Ebenezer and Gumbi, Wilson and Hotwani, Aneeta and Iqbal, Naveed and Jones, Steven M. and Kabir, Furqan and Khan, Waqasuddin and Musyani, Chileshe L. and McGann, Carolyn M. and Mittal, Varsha and Moustafa, Ahmed M. and Musicha, Patrick and Mwansa, James C.L. and Ndumba, Moreka L. and Odih, Erkison E. and Omuoyo, Donwilliams O. and Pearse, Oliver and Phillips, Laura T. and Planet, Paul J. and Rasool, Aniqa Abdul and Rodrigues, Charlene M. C. and Sands, Kirsty and Tanmoy, Arif M. and Theiller, Erin and Zuza, Allan M. and Basu, Sulagna and Chan, Grace J. and Iregbu, Kenneth C. and Mazarati, Jean-Baptiste and Alemayehu, Semaria Solomon and Walsh, Timothy R. and Zahra, Rabaab and Dramowski, Angela and Fwoloshi, Sombo and Labi, Appiah-Korang and Madrid, Lola and Obeng-Nkrumah, Noah and Ojok, David and Wadugu, Boaz D. and Whitelaw, Andrew C. and Bethou, Adhisivam and Bhargava, Anudita and Jindal, Atul and Nanavati, Ruchi N. and Prasad, Priyanka S. and Sastry, Apurba and Farooqi, Joveria Q. and Ghanchi, Najia and Jehan, Fyezah and Khan, Erum and Agarwal, Ramesh K. and Aiken, Alexander M. and Berkley, James A. and Coffin, Susan E. and Feasey, Nicholas A. and Govender, Nelesh P. and Hamer, Davidson H. and Madhi, Shabir A. and Nisar, Muhammad Imran and Saha, Samir K. and Saha, Senjuti and Sankar, Mari Jeeva and Wyres, Kelly L. and Holt, Kathryn E. (2026) Distribution of capsule and O types in Klebsiella pneumoniae causing neonatal sepsis in Africa and South Asia : A meta-analysis of genome-predicted serotype prevalence to inform potential vaccine coverage. PLOS Medicine, 23 (1). e1004879. ISSN 1549-1277 (https://doi.org/10.1371/journal.pmed.1004879)

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Abstract

Background: Klebsiella pneumoniae causes ~20% of sepsis in neonates, with ~40% crude mortality. A vaccine administered to pregnant women, protecting against ≥70% of K. pneumoniae infections, could avert ~400,000 cases and ~80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design. Methods and findings: We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20 K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and ≥70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5–10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n = 14 types). We estimate the top-5 (O1⍺β,2⍺, O1⍺β,2β, O2⍺, O2β, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%–92% per region), while the top-10 would cover ~99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time. Conclusions: Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover ≥70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development.

ORCID iDs

Stanton, Thomas D., Keegan, Shaun P., Abdulahi, Jabir A., Amulele, Anne V., Bates, Matthew, Heinz, Eva ORCID logoORCID: https://orcid.org/0000-0003-4413-3756, Hooda, Yogesh, Hu, Weiming, Jain, Kajal, Kanwar, Samiah, Magobo, Rindidzani, Olwagen, Courtney P., Tembo, John M., Sonda, Tolbert, Strysko, Jonathan, Tigoi, Caroline C., Amin, Sameen Ahmad, Bittinger, Kyle, Cornick, Jennifer, Foster-Nyarko, Ebenezer, Gumbi, Wilson, Hotwani, Aneeta, Iqbal, Naveed, Jones, Steven M., Kabir, Furqan, Khan, Waqasuddin, Musyani, Chileshe L., McGann, Carolyn M., Mittal, Varsha, Moustafa, Ahmed M., Musicha, Patrick, Mwansa, James C.L., Ndumba, Moreka L., Odih, Erkison E., Omuoyo, Donwilliams O., Pearse, Oliver, Phillips, Laura T., Planet, Paul J., Rasool, Aniqa Abdul, Rodrigues, Charlene M. C., Sands, Kirsty, Tanmoy, Arif M., Theiller, Erin, Zuza, Allan M., Basu, Sulagna, Chan, Grace J., Iregbu, Kenneth C., Mazarati, Jean-Baptiste, Alemayehu, Semaria Solomon, Walsh, Timothy R., Zahra, Rabaab, Dramowski, Angela, Fwoloshi, Sombo, Labi, Appiah-Korang, Madrid, Lola, Obeng-Nkrumah, Noah, Ojok, David, Wadugu, Boaz D., Whitelaw, Andrew C., Bethou, Adhisivam, Bhargava, Anudita, Jindal, Atul, Nanavati, Ruchi N., Prasad, Priyanka S., Sastry, Apurba, Farooqi, Joveria Q., Ghanchi, Najia, Jehan, Fyezah, Khan, Erum, Agarwal, Ramesh K., Aiken, Alexander M., Berkley, James A., Coffin, Susan E., Feasey, Nicholas A., Govender, Nelesh P., Hamer, Davidson H., Madhi, Shabir A., Nisar, Muhammad Imran, Saha, Samir K., Saha, Senjuti, Sankar, Mari Jeeva, Wyres, Kelly L. and Holt, Kathryn E.; Grais, Rebecca F.
CORE (COnnecting REpositories)