Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones ofKlebsiella pneumoniaeand stresses the importance to include temporal patterns for vaccine design considerations

Abstract

Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistantKlebsiella pneumoniaeas 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 ofKlebsiella pneumoniaecan inform management strategies but data from sub-Saharan Africa are lacking.We present a longitudinal analysis of all invasiveK. pneumoniaeisolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998-2020, combining clinical data with genome sequence analysis of the isolates. We show that after a dramatic increase in the number of infections from 2016K. pneumoniaebecomes 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.Our data highlight a clear need for new interventions to prevent rather than treatK. pneumoniaeinfections 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.