Almost all Salmonella Typhi strains isolated in France are referred to the FNRC-Salm. Most isolates were obtained from travelers or immigrants, most of whom were infected in Africa and Asia. In Cameroon, the Centre Pasteur du Cameroun collects Salmonella Typhi isolates from several hospitals in Yaoundé.

Antimicrobial susceptibility testing was performed according to the guidelines of the antibiogram committee of the French Society for Microbiology (http://www.sfm.asso.fr/nouv/general.php?pa = 2). Isolates were considered to be MDR if they were resistant to ≥2 of the following antimicrobial drugs: amoxicillin, co-trimoxazole (trimethoprim/sulfamethoxazole), chloramphenicol, or tetracyclines.

During 1996–2013, a total of 1,746 Salmonella Typhi isolates were collected through the French national surveillance system and subjected to antimicrobial susceptibility testing; 408 were acquired in sub-Saharan Africa (n = 237) and northern Africa (n = 171), and 55 (13.5%) of those acquired in Africa were MDR (Table). All but 1 of the MDR isolates were acquired in sub-Saharan Africa (Table). The proportion of MDR isolates increased from 0% during 1996–1999 to 22.3% (n = 23) during 2010–2013. Only 4 isolates from Africa were resistant to nalidixic acid, including 1 isolate resistant to ciprofloxacin. Because these isolates acquired after 2010 were not MDR isolates, they were not studied further.

In Yaoundé, the proportion of MDR isolates was high (45.5 %, 29/61) in the first survey during 2000–2004. However, this proportion increased to 75.5% (37/49) during 2010–2013.

We studied 61 isolates (Technical Appendix). Of these, 46 were MDR: 29 acquired in Africa and detected at FNRC-Salm before 2010; 2 acquired in France during 2009 at an African festive meal (13); 12 randomly selected acquired in Yaoundé during 2002–2007; 2 acquired in the Central African Republic, and 1 acquired in Morocco (2). The remaining 15 comparison strains (MDR or drug susceptible) that belonged to various haplotypes and were acquired in Africa and Asia during 1958–2009.

Mechanisms of antimicrobial drug resistance were determined as described (14). Genetic diversity and phylogenetic relationships were studied by using standardized XbaI–pulsed-field gel electrophoresis (PFGE) (http://www.cdc.gov/pulsenet/pathogens/index.html), haplotyping (5), and clustered regularly interspaced short palindromic repeats (CRISPR) typing (15). Haplotyping was based on identification of SNPs at 1,487 defined chromosomal loci, and CRISPR typing was based on detection of 32-bp sequences (spacers) within 1 or both CRISPR regions.

Figure 1

Figure 1. Characteristics of 50 Salmonella enterica serotype Typhi isolates. The dendrogram was generated by using BioNumerics version 6.6 software (Applied Maths, Sint-Martens-Latem, Belgium) and shows results of cluster analysis on the basis...

Figure 2

Figure 2. Distribution of multidrug-resistant Salmonella enterica serotype Typhi isolates by genetic lineage (A, B, or C), Gulf of Guinea region, Africa. Location within the country of infection/isolation was assigned at random. UAE,...

With the exception of the isolate from Morocco (ISP-03-07467) (2), none of the isolates had the H58 haplotype or contained the associated incHI1 pST6 MDR plasmid. We found 3 other lineages with different geographic distributions and MDR plasmids (Figures 1, 2).

Lineage A consisted mostly of haplotype H56 isolates and more rarely H42 (which differs from H56 by 2 SNPs) and was found only in the western part of the Gulf of Guinea region. Lineage B consisted of haplotype H55 isolates and was found in the eastern and southern parts of the Gulf of Guinea region. Lineage C consisted of haplotype H77 isolates and was found only in Cameroon. All 3 lineages had distinctive CRISPR1 spacer contents. XbaI-PFGE, which used a similarity value of ≥90% as a cutoff, correctly grouped (i.e., concordant with haplotyping and CRISPR results) all but 2 of the MDR isolates from Africa (Figure 1; Technical Appendix).

The 3 lineages contained a large (≈190 kb) conjugative MDR incHI1 pST2 plasmid that differed among lineages. Resistance to trimethoprim was encoded by different class 1 integron gene cassettes: dfrA15, dfrA7, and dfrA1 for incHI1 plasmids of lineages A, B, and C, respectively. All incHI1 plasmids from lineage A encoded resistance to chloramphenicol, and none of those from lineage C encoded such resistance. A second smaller (50-kb) MDR plasmid belonging to the incN incompatibility group (pST3 by plasmid multilocus sequence typing), was present mostly in lineage C isolates, but was also found in 1 lineage A isolate (02-1739) (Technical Appendix).

Analysis of older isolates and previously published data (2) showed that susceptible Salmonella Typhi strains of haplotypes H42, H56, and H77 had already been identified in Senegal in 1962, Tunisia in 1969, and Cameroon in 1958, respectively. This finding suggests that the MDR isolates from lineages A and C are derived from local Salmonella Typhi populations in Africa, rather than being recently imported from other regions to which this bacterium is endemic. Haplotype H55 was previously restricted largely to the Indian subcontinent and eastern Africa (2); it was detected in association with an incHI1 pST2 plasmid in India during the mid-1970s (5). Therefore, lineage B might have been was imported into central Africa from eastern Africa/southern Asia.

A previous study also reported isolation of an MDR clone in the Democratic Republic of the Congo in 2004 that was resistant to quinolones, showed decreased susceptibility to ciprofloxacin, and belonged to the Asian H58 lineage (2). Because only a limited number of isolates from central Africa were tested in our study, studies of a larger collection of isolates might provide more information about bacterial genotypes/MDR plasmids circulating in central Africa.

Despite intrinsic limitations of a laboratory surveillance system for typhoid fever that is used mostly for travelers and immigrants and has the bias of preferential links caused by colonial history and choices of tourist destinations, we documented emergence of 3 MDR Salmonella Typhi lineages in the Gulf of Guinea area. Two lineages found in Guinea and Cameroon were local lineages that acquired MDR conjugative plasmids, either a large incHI1 pST2 plasmid or a smaller incN pST3 plasmid. The H58 lineage, which is currently predominant in Asia and eastern Africa, was not detected among MDR isolates from West and central Africa.