ABSTRACT
Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates.
Subject(s)
Cholera/epidemiology , Cholera/microbiology , Vibrio cholerae O1/genetics , Vibrio cholerae O1/pathogenicity , Virulence/genetics , Alleles , Animals , Biological Evolution , Cholera Toxin/genetics , Epidemics , Genes, Regulator/genetics , Genetic Variation/genetics , Haiti/epidemiology , Hemolysin Proteins/genetics , Mice , Mice, Inbred ICR , Phenotype , PhylogenyABSTRACT
BACKGROUND AND AIMS: Current data on the epidemiology of cancer in the Republic of Suriname are scant and incomplete. In this study, incidence rates of the histopathologically confirmed malignancies in the country from 1980 through 2000 were inventoried. PATIENTS AND METHODS: Numbers of diagnoses, as well as patient information, were acquired from the Pathology Laboratory. The General Bureau of Statistics of Suriname provided relevant demographic information. For each year, crude incidence and sex-specific rates were calculated for: cancer overall; the most frequent cancer sites; age strata 0-19, 20-49, and 50+ years; as well as for the presumably largest, second largest, and third largest ethnic group, viz. the Hindustani, Creole, and Javanese. From these data, average rates were calculated, which were expressed as mean +/- SD per 100,000 population per year, or per 100,000 males or females per year. RESULTS: Average yearly crude and sex-specific incidence rates for cancer overall were 70 +/- 12: 59 +/- 9 for men and 83 +/- 12 for women. The leading cancer sites were cervix uteri (sex-specific rate of 22.1 +/- 5.1) as well as gastrointestinal tract, breast, hematological system, prostate, head and neck, lung, and liver (sex-specific rates ranging from 2 to 17). The relatively high rate of cervical cancer was for an important part responsible for the 1.4-fold female over male overall cancer excess. Incidence rates of most cancers increased from age group 20-49 years on, being highest after age 50+ years, but hematological malignancies occurred in all age groups with rates of 1-3 new cases per 100,000 males or females per year. Cancer was in general 2-6 times more common in Creole than in Hindustani and Javanese. However, cervical cancer was seen as often in Hindustani as in Creole. Most cases of primary liver cancer involved, besides Creole of both genders, Javanese males. Thyroid cancer occurred more frequently in Hindustani women. CONCLUSIONS: The data from the study suggest that the incidence profile of cancer in Suriname may resemble that of most developing countries. It was relatively low for cancer overall as well as for most individual sites, but relatively high for cervical cancer, thus producing the characteristic female over male excess. More detailed studies on the peculiarities in the ethnic distribution of cancer may help to shed more light on the etiology of certain malignancies.