TY - JOUR
T1 - Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones of Klebsiella pneumoniae and stresses the importance to include temporal patterns for vaccine design considerations
AU - Heinz, Eva
AU - Pearse, Oliver
AU - Zuza, Allan
AU - Bilima, Sithembile
AU - Msefula, Chisomo
AU - Musicha, Patrick
AU - Siyabu, Patriciah
AU - Tewesa, Edith
AU - Graf, Fabrice E.
AU - Lester, Rebecca
AU - Lissauer, Samantha
AU - Cornick, Jennifer
AU - Lewis, Joseph M.
AU - Kawaza, Kondwani
AU - Thomson, Nicholas R.
AU - Feasey, Nicholas A.
PY - 2024/5/6
Y1 - 2024/5/6
N2 - Background: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. Methods: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. Results: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. Conclusions: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.
AB - Background: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. Methods: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. Results: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. Conclusions: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.
KW - AMR
KW - Capsular polysaccharide
KW - ESKAPE
KW - Genome surveillance
KW - Healthcare-associated
KW - Malawi
KW - Neonatal infection
KW - Nosocomial infections
KW - Sepsis
KW - Surface antigens
UR - http://www.scopus.com/inward/record.url?scp=85192167244&partnerID=8YFLogxK
UR - https://www.ebi.ac.uk/ena/browser/view/PRJEB42462
UR - https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1102521
UR - https://github.com/EvitaH/QECHospitalKlebs; https://doi.org/10.5281/zenodo.8421658
U2 - 10.1186/s13073-024-01342-3
DO - 10.1186/s13073-024-01342-3
M3 - Article
AN - SCOPUS:85192167244
VL - 16
JO - Genome Medicine
JF - Genome Medicine
IS - 1
M1 - 67
ER -