Abstract
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.
Highlights
Chikungunya virus (CHIKV) is a positive sense single-stranded RNA alphavirus, primarily transmitted by vectors such as mosquitoes, Aedes aegypti and Aedes albopictus.[1,2] Chikungunya’s name derives from the Bantu language (Makonde ethnic group from Tanzania and Mozambique) where CHIKV was first described in 1952 and refers to a body posture showing inability to walk and debilitating joint pain.[3,4] Estimates indicate that ~2 million people were reported to be infected by CHIKV during outbreaks in the 2000s.[5]The first autochthonous CHIKV epidemic in America and the Caribbean was reported on the island of Saint Martin at the end of 2013.[2]
It is well known that people respond differently to infection, our results showed that these differences are not arbitrary and may come from the specific orchestration of our immune response and specific genetic makeup
We identified that females infected with CHIKV exhibited significant and heterogeneous phenotypic response patterns compared to men
Summary
Chikungunya virus (CHIKV) is a positive sense single-stranded RNA alphavirus, primarily transmitted by vectors such as mosquitoes, Aedes aegypti and Aedes albopictus.[1,2] Chikungunya’s name derives from the Bantu language (Makonde ethnic group from Tanzania and Mozambique) where CHIKV was first described in 1952 and refers to a body posture showing inability to walk and debilitating joint pain.[3,4] Estimates indicate that ~2 million people were reported to be infected by CHIKV during outbreaks in the 2000s.[5]. The first autochthonous CHIKV epidemic in America and the Caribbean was reported on the island of Saint Martin at the end of 2013.[2] The Asian and Eastern/Central/Southern African CHIKV strains were the agents causing the epidemic outbreak.[3] In September 2014, the Colombian health surveillance authorities reported the first autochthonous CHIKV case. The Colombian Caribbean region reported a generalized CHIKV outbreak.[6]
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