Cholera between 1991 and 1997 in Mexico was associated with infection by classical, El Tor, and El Tor variants of Vibrio cholerae

Abstract

Vibrio cholerae O1 biotype El Tor (ET), the cause of the current 7th pandemic, has recently been replaced in Asia and Africa by an altered ET biotype possessing cholera toxin (CTX) of the classical (CL) biotype that originally caused the first six pandemics before becoming extinct in the 1980s. Until recently, the ET prototype was the biotype circulating in Peru; a detailed understanding of the evolutionary trend of V. cholerae causing endemic cholera in Latin America is lacking. The present retrospective microbiological, molecular, and phylogenetic study of V. cholerae isolates recovered in Mexico (n = 91; 1983 to 1997) shows the existence of the pre-1991 CL biotype and the ET and CL biotypes together with the altered ET biotype in both epidemic and endemic cholera between 1991 and 1997. According to sero- and biotyping data, the altered ET, which has shown predominance in Mexico since 1991, emerged locally from ET and CL progenitors that were found coexisting until 1997. In Latin America, ET and CL variants shared a variable number of phenotypic markers, while the altered ET strains had genes encoding the CL CTX (CTX(CL)) prophage, ctxB(CL) and rstR(CL), in addition to resident rstR(ET), as the underlying regional signature. The distinct regional fingerprints for ET in Mexico and Peru and their divergence from ET in Asia and Africa, as confirmed by subclustering patterns in a pulsed-field gel electrophoresis (NotI)-based dendrogram, suggest that the Mexico epidemic in 1991 may have been a local event and not an extension of the epidemics occurring in Asia and South America. Finally, the CL biotype reservoir in Mexico is unprecedented and must have contributed to the changing epidemiology of global cholera in ways that need to be understood.

FIG. 1.

Dendrogram showing genomic fingerprints of V. cholerae O1 strains isolated in Mexico (1983 to 1997), North America. The dendrogram was prepared by Dice similarity coefficient and UPGMA clustering using the PFGE patterns of NotI-digested genomic DNA. The scale bar at the top shows the correlation coefficient (%). Two major clusters separating the CL biotype from the ET biotype strains show the respective lineages. The CL cluster, which includes the North American CL strains with the CL reference control strain (strain 569B), shows high degrees of divergence among the strains. The major ET cluster shows two subclusters that separate the prototype ET (Pro-ET) (including reference control strain N16961) from the altered ET (Alt-ET) strains, suggesting two different lineages for them. IN, Inaba; OG, Ogawa; Clin, clinical; Env, environmental; Edo., estado (state).

FIG. 2.

Dendrogram showing genomic fingerprints of V. cholerae O1 isolated in Mexico (1983 to 1997) and Peru (1991 to 1998), Latin America. The dendrogram (prepared by Dice similarity coefficient and UPGMA clustering) was based on the PFGE (NotI) images of genomic DNA. The two major clusters, showing the degree of similarity (%), separated the CL from the ET biotype strains, suggesting respective biotype-specific lineages. The CL biotype cluster, which includes strains exhibiting signature PFGE patterns for CL reference control strain 569B, shows high degrees of divergence among the strains. The major ET cluster shows subclusters, separating the Peruvian prototype ET (ET1) subcluster from the rest while separating the Mexican prototype ET (ET2) subcluster from the Mexican altered ET (Alt-ET), suggesting regional and type-specific fingerprints. IN, Inaba; OG, Ogawa; Clin, clinical; Env, environmental; Edo., estado (state).

FIG. 3.

Dendrogram showing genomic fingerprints of V. cholerae O1 isolates recovered in Mexico (North America) and Peru (South America) and their comparison with V. cholerae O1 isolates recovered in Bangladesh (Asia) and Zambia (Africa). Dendrogram (prepared by Dice similarity coefficient and UPGMA clustering) was based on the PFGE (NotI) patterns of genomic DNA. Two major clusters that separated the CL from the ET biotype strains, showing the degree of similarity (%), suggest biotype-specific lineages. The cluster CL includes the genetically divergent Latin American pre- and post-1991 CL strains with Asian CL strains and their reference control strain (strain 569B), suggesting the same clonal lineage for them. The major ET cluster divided the strains into four subclusters, separating the Mexican altered ET (Alt-ET1) strains from the altered ET of Asia and Africa (Alt-ET2) and Mexican prototype ET (ET1) strains from prototype ET (ET2) of Peru, depicting different signatures. IN, Inaba; OG, Ogawa; Clin, clinical; Env, environmental; Edo., estado (state).