Rapid emergence of multidrug resistant, H58-lineage Salmonella typhi in Blantyre, Malawi

• Published in: PLoS neglected tropical diseases 2015-04, Vol.9 (4), p.e0003748-e0003748
• Main Authors: Feasey, Nicholas A, Gaskell, Katherine, Wong, Vanessa, Msefula, Chisomo, Selemani, George, Kumwenda, Save, Allain, Theresa J, Mallewa, Jane, Kennedy, Neil, Bennett, Aisleen, Nyirongo, Joram O, Nyondo, Patience A, Zulu, Madalitso D, Parkhill, Julian, Dougan, Gordon, Gordon, Melita A, Heyderman, Robert S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antimicrobial agents; Bacterial infections; Base Sequence; Child; Deaths; Disease; Drug Resistance, Multiple, Bacterial - genetics; Drug therapy; Fatalities; Female; Fever; Forecasts and trends; Genotype & phenotype; Hospitals; Humans; Incidence; Infections; Laboratories; Malawi - epidemiology; Male; Medical research; Microbial drug resistance; Molecular Sequence Data; Phylogeny; Population; Prevalence; Retrospective Studies; Salmonella; Salmonella typhi; Salmonella typhi - genetics; Salmonellosis; Sanitation; Sequence Analysis, DNA; Studies; Tropical diseases; Typhoid; Typhoid Fever - epidemiology; Typhoid Fever - microbiology; Water pollution; Water quality
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0003748

Between 1998 and 2010, S. Typhi was an uncommon cause of bloodstream infection (BSI) in Blantyre, Malawi and it was usually susceptible to first-line antimicrobial therapy. In 2011 an increase in a multidrug resistant (MDR) strain was detected through routine bacteriological surveillance conducted at Queen Elizabeth Central Hospital (QECH). Longitudinal trends in culture-confirmed Typhoid admissions at QECH were described between 1998-2014. A retrospective review of patient cases notes was conducted, focusing on clinical presentation, prevalence of HIV and case-fatality. Isolates of S. Typhi were sequenced and the phylogeny of Typhoid in Blantyre was reconstructed and placed in a global context. Between 1998-2010, there were a mean of 14 microbiological diagnoses of Typhoid/year at QECH, of which 6.8% were MDR. This increased to 67 in 2011 and 782 in 2014 at which time 97% were MDR. The disease predominantly affected children and young adults (median age 11 [IQR 6-21] in 2014). The prevalence of HIV in adult patients was 16.7% [8/48], similar to that of the general population (17.8%). Overall, the case fatality rate was 2.5% (3/94). Complications included anaemia, myocarditis, pneumonia and intestinal perforation. 112 isolates were sequenced and the phylogeny demonstrated the introduction and clonal expansion of the H58 lineage of S. Typhi. Since 2011, there has been a rapid increase in the incidence of multidrug resistant, H58-lineage Typhoid in Blantyre. This is one of a number of reports of the re-emergence of Typhoid in Southern and Eastern Africa. There is an urgent need to understand the reservoirs and transmission of disease and how to arrest this regional increase.