Molecular analysis suggests multi-drug-resistant typhoid common in Nigeria

Typhoid fever is a major cause of illness and death worldwide, with more than 20 million estimated cases and over 200,000 deaths per year. The disease is caused by Salmonella Typhi bacteria and can be treated with antibiotics. Antibiotic resistance, however, is a growing problem. A study published in PLOS Neglected Tropical Diseases reports that many of the S. Typhi isolated from children in Nigeria, are resistant to multiple antibiotics.

S. Typhi has limited genome variation and this has, until recently, limited the ability to identify specific strains of the bacteria and follow their transmission patterns. However, whole genome sequencing can identify different S. Typhi 'genotypes' and reveal how important genetic traits such as antimicrobial resistance spread.

In the present study, Vanessa Wong from the Wellcome Trust Sanger Institute in Hinxton, UK, and colleagues sequenced and analyzed the genomes of 128 samples of S. Typhi isolated from the blood of infected children in two regions of Nigeria. They also compared the genomes of the Nigerian isolates with that of the S. Typhi reference strain and a global collection of approximately 2,000 S. Typhi isolates from 63 countries.

The researchers found substantial variation among the Nigerian isolates, which fell into several different genotypes. Most of the sequences were similar to other African isolates and closely related to sequences from neighboring Cameroon and across West Africa. The presence of multiple genotypes in the two comparatively small regions in Nigeria suggests that typhoid has circulated among these populations for some time, and that several waves of disease have entered the regions at different times.

Multi-drug resistance (MDR) was common in the Nigerian isolates, with many of the resistance genes found on so-called plasmids. These are circular molecules of DNA that, in addition to being passed on to bacterial daughter cells after cell division, can also been passed 'horizontally' between bacteria - even between bacteria of different species - and so cause rapid spread of antimicrobial resistance in disease-causing pathogens.

Surprisingly, the multi-drug resistant genotype H58 was not found in the Nigerian isolates. H58 S. Typhi have caused serious typhoid outbreaks in various African countries, are currently expanding across many regions with endemic typhoid, but apparently have not yet reached Nigeria.

Based on their results, the researchers conclude, "it is clear that typhoid associated with MDR S. Typhi is common in these parts of Nigeria and that the MDR phenotype is evolving independently of haplotype H58, which has emerged elsewhere in the world where typhoid is endemic". They consider it "likely that H58 S. Typhi will reach Nigeria in the future, potentially changing the epidemiology of the disease in the region", and suggest that "molecular surveillance could be used to monitor for this".

Overall, they say the study "emphasizes the importance of surveillance to improve our understanding of the epidemiology of typhoid, which is needed to underpin public health measures to reduce the spread of disease and facilitate patient management".

Article: Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa, Vanessa K. Wong et al., PLOS Neglected Tropical Diseases, doi:10.1371/journal.pntd.0004781, published 22 September 2016.