Rapid Emergence of Multidrug Resistant, H58-Lineage Salmonella Typhi in Blantyre, Malawi

Abstract

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. Typhoid fever is a major cause of disease and death around the world, particularly in resource limited settings, although reports suggest that until recently it has been much less prominent in sub-Saharan Africa (SSA) than Asia. Estimates of the precise burden of this disease are, however, difficult, as diagnosis requires advanced laboratory diagnostics. This is a particular problem in much of SSA where long-term laboratory surveillance has been available in just a few settings. Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi is one such setting; between 1998 and 2010, cases of Typhoid fever at QECH were both uncommon and responsive to all antibiotics. In 2011 a marked increase in highly antibiotic resistant Typhoid fever began, with 843 confirmed cases in 2013. A review of cases revealed that one in 40 patients died and one in five had complicated disease. A further study of the DNA of bacteria associated with the outbreak revealed a novel strain, common to Asia, has arrived in Malawi. This is one of a number of reports of the re-emergence of Typhoid fever 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.