Typhoid in Kenya is associated with a dominant multidrug-resistant Salmonella enterica serovar Typhi haplotype that is also widespread in Southeast Asia.
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.
Kariuki
Samuel
S
Centre for Microbiology Research, Kenya Medical Research Institute, P.O. Box 43640-00100, Nairobi, Kenya. skariuki@kemri.org
Revathi
Gunturu
G
Kiiru
John
J
Mengo
Doris M
DM
Mwituria
Joyce
J
Muyodi
Jane
J
Munyalo
Agnes
A
Teo
Yik Y
YY
Holt
Kathryn E
KE
Kingsley
Robert A
RA
Dougan
Gordon
G
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*
D000900:Anti-Bacterial Agents
Science. 2006 Nov 24;314(5803):1301-4
17124322
Int J Infect Dis. 2006 Nov;10(6):434-8
16978898
J Clin Microbiol. 2004 Apr;42(4):1477-82
15070992
Emerg Infect Dis. 2000 Nov-Dec;6(6):649-51
11076726
Bull World Health Organ. 2004 May;82(5):346-53
15298225
Antimicrob Agents Chemother. 2008 Apr;52(4):1278-84
18212096
Curr Issues Mol Biol. 2003 Oct;5(4):113-22
12921226
Trop Doct. 2007 Oct;37(4):231-3
17988489
BMC Microbiol. 2006 Dec 15;6:101
17173674
Am J Trop Med Hyg. 2006 Jan;74(1):114-9
16407354
J Clin Microbiol. 2000 Feb;38(2):895-7
10655411
Lancet. 1998 Jan 31;351(9099):339
9652619
Popul Health Metr. 2008 Mar 10;6:1
18331630
S Afr Med J. 1992 Mar 7;81(5):280-1
1542825
Bioinformatics. 2006 Nov 1;22(21):2688-90
16928733
Antimicrob Agents Chemother. 2009 Feb;53(2):716-27
19015365
BMC Infect Dis. 2005 Jun 21;5:49
15969764
FEMS Microbiol Lett. 2002 Oct 8;215(2):249-53
12399042
Clin Infect Dis. 2005 Feb 15;40(4):554-61
15712078
J Clin Microbiol. 2000 Apr;38(4):1449-52
10747124
J Med Microbiol. 2007 Jan;56(Pt 1):136-137
17172529
J Clin Microbiol. 2007 Nov;45(11):3485-92
17728470
Nat Genet. 2008 Aug;40(8):987-93
18660809
J Trop Med Hyg. 1989 Aug;92(4):272-5
2760970
Antimicrob Agents Chemother. 2006 Oct;50(10):3516-7
17005846
J Clin Microbiol. 2008 May;46(5):1741-6
18322069
Public Health. 2005 Apr;119(4):321-7
15733694
Trans R Soc Trop Med Hyg. 2007 Mar;101(3):308-10
16950486
Lancet. 1998 Apr 25;351(9111):1289
9643778