Cholera: under diagnosis and differentiation from other diarrhoeal diseases.

BACKGROUND: Globally 1.4 billion people are at risk from cholera in countries where the disease is endemic, with an estimated 2.8 million cases annually. The disease is significantly under reported due to economic, social and political disincentives as well as poor laboratory resources and epidemiological surveillance in those regions. In addition, identification of cholera from other diarrhoeal causes is often difficult due to shared pathology and symptoms with few reported cases in travellers from Northern Europe. METHODS: A search of PubMed and Ovid Medline for publications on cholera diagnosis from 2010 through 2017 was conducted. Search terms included were cholera, Rapid Diagnostic Test (RDT), multiplex PCR and diagnosis of diarrhoea. Studies were included if they are published in English, French or Spanish. RESULTS: An increase of RDT study publications for diarrhoeal disease and attempted test validations were seen over the publication period. RDTs were noted as having varied selectivity and specificity, as well as associated costs and local resource requirements that can prohibit their use. CONCLUSIONS: Despite opportunities to employ RDTs with high selectivity and specificity in epidemic areas, or in remote locations without access to health services, such tests are limited to surveillance use. This may represent a missed opportunity to discover the true global presence of Vibrio cholerae and its role in all cause diarrhoeal disease in underdeveloped countries and in travellers to those areas. The wider applicability of RDTs may also represent an opportunity in the wider management of traveller's diarrhoea.

An assessment of a variant of the DNA repair gene XRCC3 as a possible nevus or melanoma susceptibility genotype.

Inheritance of the T allele in exon 7 (position 18067) of the DNA repair gene XRCC3 has been reported to be associated with susceptibility to melanoma in a study from Oxford. We report a study in which an attempt was made to confirm this association in a similar population. The most potent risk factor for melanoma in the general population is a phenotype characterized by the presence of multiple melanocytic nevi: the atypical mole syndrome. Our hypothesis is that the atypical mole syndrome may be a marker of genetic susceptibility to melanoma. We have therefore investigated whether the XRCC3 polymorphism influences the nevus phenotype. The XRCC3 genotype was investigated using PCR in a general-practice-based sample of 565 women and 475 patients from a cohort enriched for the atypical mole syndrome, of whom 140 had had melanoma. Allele frequencies were the same in the healthy women, the melanoma cases from this study, and the melanoma cases reported in the Oxford study, but were different from those in the Oxford control group. We found no evidence therefore that the T allele of this XRCC3 polymorphism is indicative of susceptibility to melanoma. There was a marginal relationship with nevus phenotype, but this was no longer statistically significant in multivariate analysis. The previous association between XRCC3 and melanoma may be a result of the choice of control group and we emphasize the need for appropriate choice of controls.

An assessment of the CDKN2A variant Ala148Thr as a nevus/melanoma susceptibility allele.

Melanocytic nevi are the most potent risk factors for melanoma yet identified. Variation in the nevus phenotype within a population is predominantly genetically determined. Genes that determine nevus expression may therefore act as low penetrance melanoma susceptibility genes. Rare germline mutations in CDKN2A predispose to melanoma and appear to be nevogenic, although the correlation between nevus phenotype and mutation status is poor. It is plausible that more common CDKN2A variants may influence both melanoma susceptibility and nevus susceptibility. Ala148Thr is a G to A missense polymorphism of CDKN2A, which is found in 4%-6% of the general population. We have investigated the role of Ala148Thr as a low penetrance melanoma or nevus susceptibility allele in two separate groups of individuals. The first was a sample of 488 adults recruited from 179 families of patients with the atypical nevus phenotype and/or a family history of melanoma, and the second was a population-based sample of 599 women. Similar prevalences of Ala148Thr (4.9% and 5.2%) were found in both samples but significant variation in the prevalence of the polymorphism was seen across geographic areas within England. There was no association between Ala148Thr status and nevus number or history of melanoma, and therefore the results did not support the hypothesis that the Ala148Thr variant is a low penetrance melanoma or nevus susceptibility allele. A significant protective role of Ala148Thr on the number of atypical nevi was observed in the family sample (mean of 1 atypical nevus in those with the allele and 3.5 nevi in those without, p = 0.02). After allowing for potential confounders this was not evident in the population-based sample.