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TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya.

ABSTRACT: BACKGROUND: Squamous Cell Carcinoma of Esophagus is one of the most common malignancies in both men and women in eastern and south-eastern Africa. In Kenya, clinical observations suggest that this cancer is frequent in the Rift Valley area. However, so far, there has been no report on the molecular characteristics of esophageal squamous cell carcinoma (ESCC) in this area. RESULTS: We have analyzed TP53 mutations, the presence of human papilloma virus (HPV) DNA and expression of inflammation markers Cyclooxygenase 2 (Cox-2) and Nitrotyrosine (NTyR) in 28 cases (13 males and 15 females) of archived ESCC tissues collected at the Moi Teaching and Referral Hospital in Eldoret, Kenya. Eleven mutations were detected in TP53 exons 5 to 8 (39%). All ESCC samples were negative for HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82. Immunohistochemical analysis of Cox-2 and NTyR showed a low proportion of positive cases (17.4% and 39.1%, respectively). No association between the above markers and suspected risk factors (alcohol or tobacco use, hot tea drinking, use of charcoal for cooking) was found. CONCLUSION: Our findings suggest that mechanisms of esophageal carcinogenesis in eastern Africa might be different from other parts of the world. Low prevalence of TP53 mutation compared with other intermediate or high incidence areas of the world highlights this hypothesis. Our data did not support a possible ole of HPV in this series of cases. Further studies are needed to assess and compare the molecular patterns of ESCC from Kenya with those of high-incidence areas such as China or Central Asia.

SUBMITTER: Patel K

PROVIDER: S-EPMC3216406 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya.

Patel Kirtika K Mining Simeon S Wakhisi Johnston J Gheit Tarik T Tommasino Massimo M Martel-Planche Ghislaine G Hainaut Pierre P Abedi-Ardekani Behnoush B

BMC research notes 20111031

<h4>Background</h4>Squamous Cell Carcinoma of Esophagus is one of the most common malignancies in both men and women in eastern and south-eastern Africa. In Kenya, clinical observations suggest that this cancer is frequent in the Rift Valley area. However, so far, there has been no report on the molecular characteristics of esophageal squamous cell carcinoma (ESCC) in this area.<h4>Results</h4>We have analyzed TP53 mutations, the presence of human papilloma virus (HPV) DNA and expression of infl ...[more]

PMID: 22040862

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Project description:BackgroundThe impacts of vaccination on the transmission of Rift Valley fever virus (RVFV) have not been evaluated. We have developed a RVFV transmission model comprising two hosts-cattle as a separate host and sheep and goats as one combined host (herein after referred to as sheep)-and two vectors-Aedes species (spp) and Culex spp-and used it to predict the impacts of: (1) reactive vaccination implemented at various levels of coverage at pre-determined time points, (2) targeted vaccination involving either of the two host species, and (3) a periodic vaccination implemented biannually or annually before an outbreak.Methodology/principal findingsThe model comprises coupled vector and host modules where the dynamics of vectors and hosts are described using a system of difference equations. Vector populations are structured into egg, larva, pupa and adult stages and the latter stage is further categorized into three infection categories: susceptible, exposed and infectious mosquitoes. The survival rates of the immature stages (egg, larva and pupa) are dependent on rainfall densities extracted from the Tropical Rainfall Measuring Mission (TRMM) for a Rift Valley fever (RVF) endemic site in Kenya over a period of 1827 days. The host populations are structured into four age classes comprising young, weaners, yearlings and adults and four infection categories including susceptible, exposed, infectious, and immune categories. The model reproduces the 2006/2007 RVF outbreak reported in empirical surveys in the target area and other seasonal transmission events that are perceived to occur during the wet seasons. Mass reactive vaccination strategies greatly reduce the potential for a major outbreak. The results also suggest that the effectiveness of vaccination can be enhanced by increasing the vaccination coverage, targeting vaccination on cattle given that this species plays a major role in the transmission of the virus, and using both periodic and reactive vaccination strategies.Conclusion/significanceReactive vaccination can be effective in mitigating the impacts of RVF outbreaks but practically, it is not always possible to have this measure implemented satisfactorily due to the rapid onset and evolution of RVF epidemics. This analysis demonstrates that both periodic and reactive vaccination ought to be used strategically to effectively control the disease.

Project description:BackgroundMosquito-borne Rift Valley fever virus (RVFV) causes acute, often severe, disease in livestock and humans. To determine the exposure factors and range of symptoms associated with human RVF, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Kenya.Methodology/principal findingsA systematic survey of the total populations of six Northeastern Kenyan villages was performed. Among 1082 residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13-17%). Prevalence did not vary significantly among villages. Subject age was a significant factor, with 31% (154/498) of adults seropositive vs. only 2% of children ?15 years (12/583). Seroprevalence was higher among men (18%) than women (13%). Factors associated with seropositivity included a history of animal exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and eye symptoms. Using cluster analysis in RVFV positive participants, a more severe symptom phenotype was empirically defined as having somatic symptoms of acute fever plus eye symptoms, and possibly one or more meningoencephalitic or hemorrhagic symptoms. Associated with this more severe disease phenotype were older age, village, recent illness, and loss of a family member during the last outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93-13.61, P = 0.065), disposing of livestock abortus (aOR = 4.11, CI95% 0.63-26.79, P = 0.14), and village location (P = 0.009) were independently associated with the severe disease phenotype.Conclusions/significanceOur results demonstrate that a significant proportion of the population in northeastern Kenya has been infected with RVFV. Village and certain animal husbandry activities were associated with more severe disease. Older age, male gender, herder occupation, killing and butchering livestock, and poor visual acuity were useful markers for increased RVFV infection. Formal vision testing may therefore prove to be a helpful, low-technology tool for RVF screening during epidemics in high-risk rural settings.

Project description:Human behavioral factors have been found to be central in the transmission of Rift Valley fever. Consumption of contaminated meat and milk in particular have been identified as one of the key risk factors for the transmission of Rift Valley fever in humans. In pastoral communities, livestock is the main source of livelihood from which many benefits such as food as well as economic and cultural services are derived. Zoonotic diseases therefore have a great impact on pastoral communities livelihoods. However, lay perceptions regarding the transmission of these diseases including Rift Valley fever hampers their effective control. This study investigated the lay perceptions of risks for Rift Valley fever transmission in a pastoral community in northeastern Kenya.A qualitative study was carried out in Ijara district, Kenya which was one of the hotspots of Rift Valley during the 2006/2007 outbreak. Data were collected using focus group discussions and narratives guided by checklists. Eight focus group discussions consisting of 83 participants and six narratives were conducted. Data was transcribed, coded and analysed according to Emergent themes.The participants reported that they had experienced Rift Valley fever in their livestock especially sheep and in humans both in 1997/1998 and 2006/2007. However, they believed that infections in humans occurred as a result of mosquito bites and had little to do with their consumption of meat, milk and blood from infected livestock. The participants in this study indicated that they had heard of the risks of acquiring the disease through consumption of livestock products but their experiences did not tally with the information they had received hence to them, Rift Valley fever was not transmissible through their dietary practices.Though the communities in this region were aware of Rift Valley fever, they did not have elaborate information regarding the disease transmission dynamics to humans. To avoid misconception about transmission of the disease, intervention strategies, require to be accompanied by comprehensive explanations of the dynamics of its transmission. It is necessary to develop appropriate interventions that take into consideration, lay perceptions of risk factors for the disease and communities' livelihood strategies.

Project description:BackgroundIn endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies.Methodology/findingsWe conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006-2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI(95%):17%-29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI(95%): 20%-39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT₈₀) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤ 20/80) was much more likely in the RVFV-seropositive group (P<0.0001).ConclusionsOur results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at > 1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an important new focus for public health education during future RVF outbreaks.

Dataset Information

TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya.

Publications

TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya.

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