title: Typhoid in Kenya is associated with a dominant multidrug-resistant Salmonella enterica serovar Typhi haplotype that is also widespread in Southeast Asia.
abstract: In sub-Saharan Africa, the burden of typhoid fever, caused by Salmonella enterica serovar Typhi, remains largely unknown, in part because of a lack of blood or bone marrow culture facilities. We characterized a total of 323 S. Typhi isolates from outbreaks in Kenya over the period 1988 to 2008 for antimicrobial susceptibilities and phylogenetic relationships using single-nucleotide polymorphism (SNP) analysis. There was a dramatic increase in the number and percentage of multidrug-resistant (MDR) S. Typhi isolates over the study period. Overall, only 54 (16.7%) S. Typhi isolates were fully sensitive, while the majority, 195 (60.4%), were multiply resistant to most commonly available drugs-ampicillin, chloramphenicol, tetracycline, and cotrimoxazole; 74 (22.9%) isolates were resistant to a single antimicrobial, usually ampicillin, cotrimoxazole, or tetracycline. Resistance to these antibiotics was encoded on self-transferrable IncHI1 plasmids of the ST6 sequence type. Of the 94 representative S. Typhi isolates selected for genome-wide haplotype analysis, sensitive isolates fell into several phylogenetically different groups, whereas MDR isolates all belonged to a single haplotype, H58, associated with MDR and decreased ciprofloxacin susceptibility, which is also dominant in many parts of Southeast Asia. Derivatives of the same S. Typhi lineage, H58, are responsible for multidrug resistance in Kenya and parts of Southeast Asia, suggesting intercontinental spread of a single MDR clone. Given the emergence of this aggressive MDR haplotype, careful selection and monitoring of antibiotic usage will be required in Kenya, and potentially other regions of sub-Saharan Africa.
authors.affiliation: Centre for Microbiology Research, Kenya Medical Research Institute, P.O. Box 43640-00100, Nairobi, Kenya. skariuki@kemri.org
authors.forename: Samuel
authors.initials: S
authors.lastname: Kariuki
authors.forename: Gunturu
authors.initials: G
authors.lastname: Revathi
authors.forename: John
authors.initials: J
authors.lastname: Kiiru
authors.forename: Doris M
authors.initials: DM
authors.lastname: Mengo
authors.forename: Joyce
authors.initials: J
authors.lastname: Mwituria
authors.forename: Jane
authors.initials: J
authors.lastname: Muyodi
authors.forename: Agnes
authors.initials: A
authors.lastname: Munyalo
authors.forename: Yik Y
authors.initials: YY
authors.lastname: Teo
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001210:Asia, Southeastern / Q000453:epidemiology; D015373:Bacterial Typing Techniques; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D024901:Drug Resistance, Multiple, Bacterial; D005798:Genes, Bacterial; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D010802:Phylogeny; D010957:Plasmids / Q000032:analysis; D020641:Polymorphism, Single Nucleotide; D012485:Salmonella typhi / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D014435:Typhoid Fever / Q000453:epidemiology* / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents
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