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

INTRODUCTION: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

Maximum-likelihood tree of 112 isolates of <i>S</i>.Typhi from Malawi, placed in the context of 24 isolates representative of the global diversity of <i>S</i>. Typhi and highlighting the previous diversity of Typhi isolates and the recent clonal expansion of the H58 haplotype.

<p>The left column depicts lineage, the right column depicts time category. Scale bar reveals indicates substitutions/variable site.</p

Phenotypic antimicrobial resistance patterns (n,%) of different clades.

<p>^† Susceptible to amoxicillin, chloramphenicol, cotrimoxazole, ciprofloxacin, ceftriaxone.</p><p>*MDR: Multidrug resistant to amoxicillin, chloramphenicol, cotrimoxazole</p><p>Phenotypic antimicrobial resistance patterns (n,%) of different clades.</p

Proportion of sequenced <i>S</i>.Typhi isolates from MLW collection belonging to each haplotype, the number above each bar represents the total number sequenced for each year.

<p>Proportion of sequenced <i>S</i>.Typhi isolates from MLW collection belonging to each haplotype, the number above each bar represents the total number sequenced for each year.</p

Temporal trends in <i>S</i>. Typhi isolation and antimicrobial resistance at QECH, Blantyre 1998–2013.

<p>*MDR: Multidrug resistant to amoxicillin, chloramphenicol, cotrimoxazole</p><p>Temporal trends in <i>S</i>. Typhi isolation and antimicrobial resistance at QECH, Blantyre 1998–2013.</p

Monthly trends in bloodstream invasive <i>Salmonella</i> diagnosed at QECH from November 2010-October 2014.

<p>Monthly trends in bloodstream invasive <i>Salmonella</i> diagnosed at QECH from November 2010-October 2014.</p

Age distribution of Typhoid in Blantyre 2011–14.

<p>2A reflects the total age distribution frequency and 2B reflects the median age each year with interquartile range.</p