Chikungunya Virus Infection

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes, mostly Aedes aegypti and Aedes albopictus. After half a century of focal outbreaks of acute febrile polyarthralgia in Africa and Asia, the disease unexpectedly spread in the past decade with large outbreaks in Africa and around the Indian Ocean and rare autochthonous transmission in temperate areas. This emergence brought new insights on its pathogenesis, notably the role of the A226V mutation that improved CHIKV fitness in Ae. albopictus and the possible CHIKV persistence in deep tissue sanctuaries for months after infection. Massive outbreaks also revealed new aspects of the acute stage: the high number of symptomatic cases, unexpected complications, mother-to-child transmission, and low lethality in debilitated patients. The follow-up of patients in epidemic areas has identified frequent, long-lasting, rheumatic disorders, including rare inflammatory joint destruction, and common chronic mood changes associated with quality-of-life impairment. Thus, the globalization of CHIKV exposes countries with Aedes mosquitoes both to brutal outbreaks of acute incapacitating episodes and endemic long-lasting disorders

High rate of subclinical chikungunya virus infection and association of neutralizing antibody with protection in a prospective cohort in the Philippines.

BACKGROUND: Chikungunya virus (CHIKV) is a globally re-emerging arbovirus for which previous studies have indicated the majority of infections result in symptomatic febrile illness. We sought to characterize the proportion of subclinical and symptomatic CHIKV infections in a prospective cohort study in a country with known CHIKV circulation. METHODS/FINDINGS: A prospective longitudinal cohort of subjects ≥6 months old underwent community-based active surveillance for acute febrile illness in Cebu City, Philippines from 2012-13. Subjects with fever history were clinically evaluated at acute, 2, 5, and 8 day visits, and at a 3-week convalescent visit. Blood was collected at the acute and 3-week convalescent visits. Symptomatic CHIKV infections were identified by positive CHIKV PCR in acute blood samples and/or CHIKV IgM/IgG ELISA seroconversion in paired acute/convalescent samples. Enrollment and 12-month blood samples underwent plaque reduction neutralization test (PRNT) using CHIKV attenuated strain 181/clone25. Subclinical CHIKV infections were identified by ≥8-fold rise from a baseline enrollment PRNT titer 50 years old. Baseline CHIKV PRNT titer ≥10 was associated with 100% (95%CI: 46.1, 100.0) protection from symptomatic CHIKV infection. Phylogenetic analysis demonstrated Asian genotype closely related to strains from Asia and the Caribbean. CONCLUSIONS: Subclinical infections accounted for a majority of total CHIKV infections. A positive baseline CHIKV PRNT titer was associated with protection from symptomatic CHIKV infection. These findings have implications for assessing disease burden, understanding virus transmission, and supporting vaccine development

Impact of Chikungunya Virus Infection on Health Status and Quality of Life: A Retrospective Cohort Study

BACKGROUND:Persistent symptoms, mainly joint and muscular pain and depression, have been reported several months after Chikungunya virus (CHIKV) infection. Their frequency and their impact on quality of life have not been compared with those of an unexposed population. In the present study, we aimed to describe the frequency of prolonged clinical manifestations of CHIKV infection and to measure the impact on quality of life and health care consumption in comparison with that of an unexposed population, more than one year after infection. METHODOLOGY/PRINCIPAL FINDINGS:In a retrospective cohort study, 199 subjects who had serologically confirmed CHIKV infection (CHIK+) were compared with 199 sero-negative subjects (CHIK-) matched for age, gender and area of residence in La Réunion Island. Following an average time of 17 months from the acute phase of infection, participants were interviewed by telephone about current symptoms, medical consumption during the last 12 months and quality of life assessed by the 12-items Short-Form Health Survey (SF-12) scale. At the time of study, 112 (56%) CHIK+ persons reported they were fully recovered. CHIK+ complained more frequently than CHIK- of arthralgia (relative risk = 1.9; 95% confidence interval: 1.6-2.2), myalgia (1.9; 1.5-2.3), fatigue (2.3; 1.8-3), depression (2.5; 1.5-4.1) and hair loss (3.8; 1.9-7.6). There was no significant difference between CHIK+ and CHIK- subjects regarding medical consumption in the past year. The mean (SD) score of the SF-12 Physical Component Summary was 46.4 (10.8) in CHIK+ versus 49.1 (9.3) in CHIK- (p = 0.04). There was no significant difference between the two groups for the Mental Component Summary. CONCLUSIONS/SIGNIFICANCE:More than one year following the acute phase of infection, CHIK+ subjects reported more disabilities than those who were CHIK-. These persistent disabilities, however, have no significant influence on medical consumption, and the impact on quality of life is moderate

The Chikungunya Epidemic on La Réunion Island in 2005–2006: A Cost-of-Illness Study

For a long time, studies of chikungunya virus infection have been neglected, but since its resurgence in the south-western Indian Ocean and on La Réunion Island, this disease has been paid greater amounts of attention. The economic and social impacts of chikungunya epidemics are poorly documented, including in developed countries. This study estimated the cost-of-illness associated with the 2005–2006 chikungunya epidemics on La Réunion Island, a French overseas department with an economy and health care system of a developed country. “Cost-of-illness” studies measure the amount that would have been saved in the absence of a disease. We found that the epidemic incurred substantial medical expenses estimated at €43.9 million, of which 60% were attributable to direct medical costs related, in particular, to expenditure on medical consultations (47%), hospitalization (32%) and drugs (19%). The costs related to care in ambulatory and hospitalized cases were €90 and €2000 per case, respectively. This study provides the basic inputs for conducting cost-effectiveness and cost-benefit evaluations of chikungunya prevention strategies

Recombinant Modified Vaccinia Virus Ankara Expressing Glycoprotein E2 of Chikungunya Virus Protects AG129 Mice against Lethal Challenge

Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections

Tuning Reactivity of Bioinspired [NiFe]-Hydrogenase Models by Ligand Design and Modeling the CO Inhibition Process

International audienceDespite the report of several structural and functional models of the [NiFe]-hydrogenases, it is still unclear how the succession of electron and proton transfers during H-2 production catalysis are controlled in terms of both sequence (order of the chemical or redox steps) and sites (metal and/or ligand). To address this issue, the structure of the previously described bioinspired [NiFe]-hydrogenase complex [(LNiFII)-Ni-N2S2-F-II Cp(CO)](+) ((LNiFeCp)-Fe-II-Cp-II, with L-N2S2 = 2,2'-(2,2'-bipyridine-6,6'-diy1)bis(1,1'-diphenylethanethiolate) and Cp = cyclopentadienyl) has been fine-tuned by modifying exclusively the Fe site. In [(LNiFeCp)-Ni-N2S2-Fe-II-Cp-II* (CO)](+) ((LNiFeCp)-Fe-II-Cp-II*, with Cp* = pentamethylcyclopentadienyl), the Cp- ligand has been replaced by Cp*- to change both the redox and structural properties of the overall complex as a consequence of the steric hindrance of Cp*-. The (LNiFeCp)-Fe-II-Cp-II* complex acts as an efficient electrocatalyst to produce H-2. Density functional theory (DFT) calculations support a CEEC cycle, following an initial reduction. The initial protonation leads to the cleavage of one thiolate-iron bond and the next reduction to the generation of a bridging Fe-based hydride moiety. Interestingly, the second protonation step generates a species containing a terminal Ni-based thiol and a bridging hydride. In the presence of CO, the electrocatalytic activity of (LNiFeCp)-Fe-II-Cp-II* for H-2 production is markedly inhibited (about 90% of loss), while only a partial inhibition (about 30% of loss) is observed in the case of (LNIFeCp)-I-II-Cp-II. DFT calculations rationalized this effect by predicting that interactions of the one- and two-electron-reduced species for (LNiFeCp)-Fe-II-Cp-II* with CO are thermodynamically more favorable in comparison to those for (LNiFeCp)-Fe-II-Cp-II