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Genetic Characterization of Northwestern Colombian Chikungunya Virus Strains from the 2014-2015 Epidemic.

ABSTRACT: Chikungunya fever, an acute and often chronic arthralgic disease caused by the mosquito-borne alphavirus, chikungunya virus (CHIKV), spread into the Americas in late 2013. Since then it has caused epidemics in nearly all New World countries, the second largest being Colombia with over 450,000 suspected cases beginning in September, 2014, and focused in Bolivar Department in the north. We examined 32 human sera from suspected cases, including diverse age groups and both genders, and sequenced the CHIKV envelope glycoprotein genes, known determinants of vector host range. As expected for Asian lineage CHIKV strains, these isolates lacked known Aedes albopictus-adaptive mutations. All the Colombian strains were closely related to those from the Virgin Islands, Saint Lucia, Mexico, Puerto Rico, and Brazil, consistent with a single, point-source introduction from the southeast Asia/Pacific region. Two substitutions in the E2 and E1 envelope glycoprotein genes were found in the Colombian strains, especially E1-K211E involving a residue shown previously to affect epistatically the penetrance of the E1-A226V A. albopictus-adaptive substitution. We also identified two amino acid substitutions unique to all American CHIKV sequences: E2-V368A and 6K-L20M. Only one codon, 6K-47, had a high nonsynonymous substitution rate suggesting positive selection.

SUBMITTER: Rodas JD

PROVIDER: S-EPMC5014272 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Genetic Characterization of Northwestern Colombian Chikungunya Virus Strains from the 2014-2015 Epidemic.

Rodas Juan D JD Kautz Tiffany T Camacho Erwin E Paternina Luis L Guzmán Hilda H Díaz Francisco J FJ Blanco Pedro P Tesh Robert R Weaver Scott C SC

The American journal of tropical medicine and hygiene 20160718 3

Chikungunya fever, an acute and often chronic arthralgic disease caused by the mosquito-borne alphavirus, chikungunya virus (CHIKV), spread into the Americas in late 2013. Since then it has caused epidemics in nearly all New World countries, the second largest being Colombia with over 450,000 suspected cases beginning in September, 2014, and focused in Bolivar Department in the north. We examined 32 human sera from suspected cases, including diverse age groups and both genders, and sequenced the ...[more]

PMID: 27430542

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Project description:BackgroundIn November 2011, a government hospital physician in Shibganj sub-district of Bangladesh reported a cluster of patients with fever and joint pain or rash. A multi-disciplinary team investigated to characterize the outbreak; confirm the cause; and recommend control and prevention measures.MethodsShibganj's residents with new onset of fever and joint pain or rash between 1 September and 15 December 2011 were defined as chikungunya fever (CHIKF) suspect cases. To estimate the attack rate, we identified 16 outpatient clinics in 16 selected wards across 16 unions in Shibganj and searched for suspect cases in the 80 households nearest to each outpatient clinic. One suspect case from the first 30 households in each ward was invited to visit the nearest outpatient clinic for clinical assessment and to provide a blood sample for laboratory testing and analyses.ResultsWe identified 1,769 CHIKF suspect cases from among 5,902 residents surveyed (30%). Their median age was 28 (IQR:15-42) years. The average attack rate in the sub-district was 30% (95% CI: 27%-33%). The lowest attack rate was found in children <5 years (15%). Anti-CHIKV IgM antibodies were detected by ELISA in 78% (264) of the 338 case samples tested. In addition to fever, predominant symptoms of serologically-confirmed cases included joint pain (97%), weakness (54%), myalgia (47%), rash (42%), itching (37%) and malaise (31%). Among the sero-positive patients, 79% (209/264) sought healthcare from outpatient clinics. CHIKV was isolated from two cases and phylogenetic analyses of full genome sequences placed these viruses within the Indian Ocean Lineage (IOL). Molecular analysis identified mutations in E2 and E1 glycoproteins and contained the E1 A226V point mutation.ConclusionThe consistently high attack rate by age groups suggested recent introduction of chikungunya in this community. Mosquito control efforts should be enhanced to reduce the risk of continued transmission and to improve global health security.

Project description:Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the Togaviridae family, is part of a group of emergent diseases, including arbovirus, constituting an increasing public health problem in tropical areas worldwide. CHIKV causes a severe and debilitating disease with high morbidity. The first Colombian autochthonous case was reported in the Colombian Caribbean region in September 2014. Within the next two to three months, the CHIKV outbreak reached its peak. Although the CHIKV pattern of clinical symptomatology has been documented in different epidemiological studies, understanding of the relationship between clinical symptomatology and variation in phenotypic response to CHIKV infection in humans remains limited. We performed a cross sectional study following 1160 individuals clinically diagnosed with CHIKV at the peak of the Chikungunya outbreak in the Colombian Caribbean region. We examined the relationship between symptomatology and diverse phenotypic responses. Latent Class Cluster Analysis (LCCA) models were used to characterize patients' symptomatology and further identify subgroups of individuals with differential phenotypic response. We found that most individuals presented fever (94.4%), headache (73.28%) and general discomfort (59.4%), which are distinct clinical symptoms of a viral infection. Furthermore, 11/26 (43.2%) of the categorized symptoms were more frequent in women than in men. LCCA disclosed seven distinctive phenotypic response profiles in this population of CHIKV infected individuals. Interestingly, 282 (24.3%) individuals exhibited a lower symptomatic "extreme" phenotype and 74 (6.4%) patients were within the severe complex "extreme" phenotype. Although clinical symptomatology may be diverse, there are distinct symptoms or group of symptoms that can be correlated with differential phenotypic response and perhaps susceptibility to CHIKV infection, especially in the female population. This suggests that, comparatively to men, women are a CHIKV at-risk population. Further study is needed to validate these results and determine whether the distinct LCCA profiles are a result of the immune response or a mixture of genetic, lifestyle and environmental factors. Our findings could contribute to the development of machine learning approaches to characterizing CHIKV infection in other populations. Preliminary results have shown prediction models achieving up to 92% accuracy overall, with substantial sensitivity, specificity and accuracy values per LCCA-derived cluster.

Dataset Information

Genetic Characterization of Northwestern Colombian Chikungunya Virus Strains from the 2014-2015 Epidemic.

Publications

Genetic Characterization of Northwestern Colombian Chikungunya Virus Strains from the 2014-2015 Epidemic.

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