Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa.

BACKGROUND: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. METHODS: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. RESULTS: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. CONCLUSIONS: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid

Acquired multidrug-resistance in Nigerian <i>S</i>. Typhi isolates.

<p>Maximum likelihood tree of 128 Nigerian <i>S</i>. Typhi isolates from 2,541 SNPs is shown on the left. On the right is a heatmap which shows, for each isolate, its multidrug-resistant (MDR) status (purple), the presence of <i>gyrA</i> mutations (dark green S83Y; light green S83F), resistance genes <i>cat</i>, <i>blaTEM</i>, <i>dfrA</i>, <i>sul1/2</i>, <i>strAB</i>, <i>tetB/AR</i>, <i>qnr</i> (red) and plasmids, including IncHI1 (dark blue), Kpn3 (light blue), IncY (orange), IncQ1 (light pink), IncFIIs (yellow) and Col(RNAI) (magenta). Different colored bars within the plasmid column show isolates that harbor multiple plasmids with each bar representing a plasmid type. The absence of a genotype or plasmid was displayed in grey. Branch lengths are indicative of the estimated substitution rate per variable site.</p

Distribution of Nigerian <i>S</i>. Typhi isolates in Africa in this study.

<p>A maximum likelihood tree of 366 <i>S</i>. Typhi isolates constructed using 9,352 SNPs from whole genome sequence from 128 Nigerian isolates and 238 isolates from other regions of Africa is shown on the left. The geographical location of isolation is highlighted on the maps of Africa displayed on the right (<a href="http://microreact.org/showcase/" target="_blank">http://microreact.org/showcase/</a>). <i>S</i>. Typhi isolates from Abuja (122 isolates) and Kano (6) are denoted using red and orange squares, respectively. Colored circles on both the tree and maps represent isolates from other regions of Africa. The common genotypes of the Nigerian isolate are highlighted by a grey ring surrounding the tree with the corresponding geographical location marked on the map. Branch lengths are indicative of the estimated substitution rate per variable site.</p

Presence of antimicrobial resistance of <i>S</i>. Typhi in the study areas.

<p>The proportion of <i>S</i>. Typhi isolates that were resistant to one or more antimicrobials (red line) and were multidrug-resistant (MDR; defined as resistance to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole, blue line) are shown. Percentages are of the total <i>S</i>. Typhi isolated per year.</p