CHIKV Infection Research Articles

Enzyme-linked immunosorbent assay using recombinant envelope protein 2 antigen for diagnosis of Chikungunya virus

BackgroundChikungunya (CHIKV) virus is an important mosquito-borne virus causing outbreaks of acute febrile illness with arthropathy. The detection of specific antibodies against CHIKV is used for diagnosis after the acute viremic phase of the disease. However, a major challenge for serologic diagnosis of CHIKV and other alphaviruses is the cross-reactivity of antibodies to common antigens among these viruses. In the present study, we have developed an enzyme-linked immunosorbend assay using a recombinant envelope protein 2 of CHIKV produced in Escherichia coli system, as a capture antigen.ResultsHigh titers (1600 to 12,800) of anti-CHIKV antibodies were detected in human sera analyzed by the CHIKV assay, suggesting it may detect low levels of the antibodies presence. On the other side, cross-reactivity was not observed in mouse hyperimmune sera to Mayaro virus and other alphaviruses analyzed by the CHIKV immunosorbend assay, suggesting it is a CHIKV-specific test. Fifty-nine human serum samples of CHIKV infection suspected cases were tested for immunoglobulin G (IgG) and M (IgM) antibodies detection using the CHIKV immunosorbend assay. A total of 44% (26/59) of samples were positive for IgG to CHIKV, determining 89.66% sensitivity and 100% specificity when the assay is compared to a CHIKV-specific neutralization assay. In addition, 40.6% (24/59) of samples were positive for IgM, determining 92.48% sensitivity and 79.04% specificity by a Bayesian method in the absence of a gold standard. Moreover, CHIKV immunosorbend assay showed similar sensibilities to a commercial immunochromatography assay (Lumiquick, USA) for CHIKV IgG and IgM detection.ConclusionIn short, we have developed a rapid, simple, specific and sensitive CHIKV immunosorbend assay for IgG and IgM detection and our results showed potential applicability on the diagnosis of infections by this virus.

Pregnant women co-infected with HIV and Zika: Outcomes and birth defects in infants according to maternal symptomatology.

BackgroundZika virus (ZIKV) was first isolated in Uganda in 1947. In Brazil, the first reported case of ZIKV infection was in May 2015. Additionally, dengue (DENV) is endemic and there has been a recent outbreak of chikungunya (CHIKV). Since the clinical manifestations of different arboviral infections (AI) can be similar, definitive diagnosis requires laboratory testing.ObjectivesTo determine the prevalence of ZIKV, DENV, and CHIKV infections in a Brazilian cohort of HIV-infected pregnant women, to assess clinical/immunological characteristics and pregnancy outcomes of women with evidence of recent AI.Study designLaboratory diagnosis of ZIKV, DENV and CHIKV infections utilized serological assays, RT-PCR and PRNT. The tests were performed at the first visit, 34–36 weeks of gestation and at any time if a woman had symptoms suggestive of AI. Mann-Whitney tests were used for comparison of medians, Chi-square or Fisher’s to compare proportions; p< 0.05 was considered statistically significant. Poisson regression was used to analyze risk factors for central nervous system (CNS) malformations in the infant according to maternal symptomatology.ResultsOf 219 HIV-infected pregnant women enrolled, 92% were DENV IgG+; 47(22%) had laboratory evidence of recent AI. Of these, 34 (72%) were ZIKV+, nine (19%) CHIKV+, and two (4%) DENV+. Symptoms consistent with AI were observed in 23 (10%) women, of whom 10 (43%) were ZIKV+, eight (35%) CHIKV+. No CNS abnormalities were observed among infants of DENV+ or CHIKV+ women; four infants with CNS abnormalities were born to ZIKV+ women (three symptomatic). Infants born to ZIKV+ women had a higher risk of CNS malformations if the mother was symptomatic (RR = 7.20), albeit not statistically significant (p = 0.066).ConclusionsAmong HIV-infected pregnant women with laboratory evidence of a recent AI, 72% were ZIKV-infected. In this cohort, CNS malformations occurred among infants born to both symptomatic and asymptomatic pregnant women with Zika infection.

Chikungunya virus: genomic microevolution in Eastern India and its in-silico epitope prediction.

This is the first study reporting whole genome sequences of two CHIKV strains (KJ679577 and KJ679578) isolated from Eastern Indian patients sera during 2010-2011 outbreak, both of which were of ECSA genotype, but from different subgroups: Indian Ocean outbreak and ECSA subtypes. Furthermore, viral sequences were analyzed using different in-silico approaches to identify potential genetic variations that might have functional implications on various aspects of virus replication, viral protein functionality, immunogenicity and transmission. Epitope prediction analysis revealed 70.9% increase in number of MHC Class-II interacting epitopes of KJ679578 and 25-28% increase in Class-I interacting epitopes of KJ679577 and KJ679578 compared to that of EF027141 (CHIKV of Asian genotype circulating in India during 1973, after which CHIKV infection disappeared from India for three decades). CHIKV peptides DLAKLAFKRSSKYDLECAQIPVHMKSDA and KVVLCGDPKQCGFFNMMQMKYNYNHNI were predicted to interact with maximum number of HLA Class-I (68 and 76.5%, respectively) and Class-II (47 and 100%, respectively) alleles present within Indian population with allele frequency of > 0.1 and were also recognized as predicted B-cell epitopes with BCPred score between 0.766 and 0.961 and with antigenicity ranging from 0.52 to 1.69; thus these peptides might be used to induce T- and B-cell-mediated immunity against CHIKV. Thus, the present study might help to bridge the gap between virus microevolution and its implication in host immunity by taking into account viral genetic and conformational changes. Predicted epitopes might be used as promising targets for peptide-based vaccine development and rapid diagnostics against CHIKV infection.

Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses.

Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections.

Mxra8 is a receptor for multiple arthritogenic alphaviruses.

Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease1. The host factors required for alphavirus entry remain poorly characterized2. Using a genome-wide CRISPR/Cas9-based screen, we identified the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses including chikungunya (CHIKV), Ross River, Mayaro, and O’nyong nyong (ONNV) viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced viral infection of cells, and reciprocally, ectopic expression resulted in increased infection. Mxra8 bound directly to CHIKV particles and enhanced virus attachment and internalization into cells. Consistent with these findings, Mxra8-Fc protein or anti-Mxra8 monoclonal antibodies blocked CHIKV infection in multiple cell types including primary human synovial fibroblasts, osteoblasts, chondrocytes, and skeletal muscle cells. Mutagenesis experiments suggest that Mxra8 binds to a surface-exposed region across the A and B domains of CHIKV E2, a speculated site of attachment. Finally, administration of Mxr8a-Fc protein or anti-Mxra8 blocking antibodies reduced CHIKV or ONNV infection and associated foot swelling in mice. Pharmacological targeting of Mxra8 could form a strategy for mitigating infection and disease by multiple arthritogenic alphaviruses.

Chikungunya Virus Strains Show Lineage-Specific Variations in Virulence and Cross-Protective Ability in Murine and Nonhuman Primate Models.

ABSTRACTChikungunya virus (CHIKV) is a reemerging arbovirus capable of causing explosive outbreaks of febrile illness, polyarthritis, and polyarthralgia, inflicting severe morbidity on affected populations. CHIKV can be genetically classified into 3 major lineages: West African (WA); East, Central, and South African (ECSA); Indian Ocean (IOL); and Asian. Additionally, the Indian Ocean (IOL) sublineage emerged within the ECSA clade and the Asian/American sublineage emerged within the Asian clade. While differences in epidemiological and pathological characteristics among outbreaks involving different CHIKV lineages and sublineages have been suggested, few targeted investigations comparing lineage virulence levels have been reported. We compared the virulence levels of CHIKV isolates representing all major lineages and sublineages in the type I interferon receptor-knockout A129 mouse model and found lineage-specific differences in virulence. We also evaluated the cross-protective efficacy of the IOL-derived, live-attenuated vaccine strain CHIKV/IRESv1 against the Asian/American CHIKV isolate YO123223 in both murine and nonhuman primate models, as well as the WA strain SH2830 in a murine model. The CHIKV/IRES vaccine provided protection both in mice and in nonhuman primate cohorts against Caribbean strain challenge and protected mice against WA challenge. Taken together, our data suggest that Asian/American CHIKV strains are less virulent than those in the Asian, ECSA, and WA lineages and that despite differences in virulence, IOL-based vaccine strains offer robust cross-protection against strains from other lineages. Further research is needed to elucidate the genetic basis for variation in CHIKV virulence in the A129 mouse model and to corroborate this variation with human pathogenicity.

Chikungunya Related Sudden and Unexpected Deaths in Brazil: Is the Worst yet to Come?

Brazilian citizens and its public health system have been dealing with Aedes aegypti and dengue for more than a decade now. More recently, Zika and Chikungunya (CHIKV) viruses have arisen, sharing the same vector as dengue. Some reports initially suggested that those new arbovirosis had a better prognosis, but specially (CHIKV) infection is such a young variation of dengue that researches worldwide still need more time to understand its behaviour. The population previously exposed to the virus together with climatic changes and inadequate sanitary situation were favorable for an outbreak and then a decrease in clinical cases in Brazil. CHIKV infection can present with an acute/ subacute phase followed by a chronic condition. The acute phase has shown severe atypical manifestations mainly in people with comorbidities, increasing the risk of death. The objective of this case report is to describe the sudden and unexpected deaths of two young and healthy females presumed caused by CHIKV in a 24-hour period after admission to a Public Heath Hospital in Rio de Janeiro, Brazil. On this behalf, this more recent arbovirus infection still represents a great challenge to emergency care physicians and researchers worldwide and it seems too early to determine CHIKV acute and late prognosis. Science should be aware that CHIKV outbreak emerge as lethal as dengue or even worse.

Clinical and Laboratory Profile of Zika and Dengue Infected Patients: Lessons Learned From the Co-circulation of Dengue, Zika and Chikungunya in Brazil.

Background: The current triple epidemic caused by dengue, zika and chikungunya constitutes a serious health problem in Brazil. The aim of this study was to investigate acute samples (up to the 7 days of symptoms) from patients presenting acute fever syndrome suspected as arboviral infection and characterize the clinical and laboratorial profile during the co-circulation of dengue, zika and chikungunya in Campo Grande, Mato Grosso do Sul (MS), midwest region of Brazil. Methods: All suspected cases (n=134) were tested by using serological and molecular diagnostic tests including DENV, ZIKV and CHIKV RT-PCR, Dengue nonstructural protein 1 (NS1) antigen capture ELISA, anti- DENV IgM ELISA and anti-CHIKV IgM ELISA. In addition, clinical, hematological and biochemical parameters of infected patients were analyzed. Results: It was observed that 79.1% of the blood samples were confirmed for ZIKV and/or DENV infection Of those, 38.0% patients were DENV monoinfected, 26.8% were ZIKV monoinfected and 13.4% were DENV/ZIKV co-infected. Seven patients presented Chikungunya IgM antibodies indicating a previous CHIKV infection. Common symptoms included fever, rash, arthralgia, myalgia, prostration, headache and conjunctivitis. Statistical analysis showed that pruritus and edema were associated with ZIKV infection while prostration and vomiting were more associated with dengue. Additionally, total protein and ALT levels were significantly different in DENV patients compared to ZIKV ones. Some DENV infected patients as well as co-infected needed hospitalization and venous hydration. Otherwise, most ZIKV infected patients presented mild clinical course. Among the pregnant women studied (n=11), three were ZIKV monoinfected while four were DENV monoinfected and two were DENV-1/ZIKV coinfected. In general, normal birth outcomes were observed except for the death due to respiratory insufficiency of one baby born to a mother coinfected with DENV-1/ZIKV. Conclusions: Herein, we provide evidence of the co-circulation of DENV, ZIKV and CHIKV infections in the Campo Grande, MS, Brazil, with a high frequency of DENV-1/ZIKV coinfection. Laboratorial diagnosis poses a challenge where those arboviruses are endemic and differential diagnosis proved to imperative for cases characterization. The knowledge about disease severity during arbovirus coinfections is still scarce and there are several issues emphasizing the importance of adequate management of patients at risk areas.

The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study.

BackgroundChikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics.MethodsWe conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded.ResultsEthnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk.ConclusionsThese data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.

Outbreak of chikungunya virus in a vulnerable population of Sergipe, Brazil—A molecular and serological survey

BackgroundChikungunya virus (CHIKV) is a re-emerging arbovirus that is causing outbreaks in several countries of the Americas. The virus was introduced in Brazil in 2014, and since then, several Brazilian states have notified autochthonous cases. ObjectivesProvide additional evidence on a CHIKV outbreak and an outline of the laboratory and clinical profile of symptomatic patients in Sergipe, Brazil. Study designIn February 2016, we collected 142 serum samples from symptomatic patients for arboviruses in Sergipe, Brazil. All samples were submitted to qRT-PCR for the emerging arboviruses circulating in Brazil – ZIKV, CHIKV, and DENV – and later submitted to the immunoenzymatic assay. RNA positive samples were randomly selected and sequenced for characterization of the genotype involved in the outbreak. ResultsOur study had 75.35% (107/142) positivity for CHIKV infection, with all age groups and genera being equally infected. The virus was identified in 11 of the 13 cities studied in that state, including the ECSA genotype. Importantly, fever was the only statistically significant symptoms for CHIKV infection (p<0.05), while asthenia was significantly associated with symptomatic patients that were CHIKV-negative (p<0.05). ConclusionsOur findings support the importance of fever as a clinical marker and contribute to molecular and serological surveillance data, which may help in the understanding of CHIKV circulation, emergence and clinical description.

Chikungunya Infection in Solid Organ Transplant Recipients

BackgroundChikungunya virus (CHIKV) is an emerging mosquito-borne disease that causes acute febrile polyarthralgia and arthritis. CHIKV has spread rapidly to the Americas and, in Brazil, autochthonous cases are increasingly been reported. Solid organ transplant (SOT) recipients who travel to or live in CHIKV endemic areas are under high risk of acquiring the disease. Few data exist regarding the clinical characteristics of CHIKV infections in this population. We report the first case series of CHIKV infection in SOT recipients. MethodsWe retrospectively evaluated 13 cases of CHIKV infection in SOT recipients between January 2016 and December 2016 confirmed by laboratory tests and transplanted in the Renal and Liver Transplant Units of Walter Cantídio University Hospital from Federal University of Ceará. ResultsPositive CHIKV serology (enzyme-linked immunosorbent assay immunoglobulin M) was found in all patients (9 kidney and 4 liver transplant recipients). All of these patients had been living in endemic areas for dengue and CHIKV in the past months before the illness. The mean time between transplantation and CHIKV infection was of 7.2 years. Fever presented in 11 (84.6%) patients and 5 (38.5%) presented with a maculopapular rash. All cases had joint symptoms: 11 (84.6%) with symmetrical and peripheral polyarthralgia/polyarthritis and 2 (15.3%) with monoarthralgia/monoarthritis. Six (46%) patients had a joint complaint that lasted 3 months. Two patients had concomitant positive dengue serology (enzyme-linked immunosorbent assay immunoglobulin M). There were no cases of complications or deaths. ConclusionSOT with CHIKV infection seems to have a clinical presentation and evolution similar to those seen in the general population, with no apparent damage to the graft.

Poverty and Arbovirus Outbreaks: When Chikungunya Virus Hits More Precarious Populations Than Dengue Virus in French Guiana.

BackgroundSince 2013, 3 successive arbovirus outbreaks, dengue (DENV), chikungunya (CHIKV), and Zika virus, have occurred in French Guiana (FG). The primary objective of this study was to describe the socioeconomic indicators of the first patients infected with CHIKV during the outbreak of 2014. The secondary objective was to compare those patients with patient infected by DENV and with the local population.MethodsA monocentric, retrospective, case-control study was conducted in Cayenne hospital in FG comparing a group of patients infected with CHIKV in 2014 with a group infected with DENV in 2013. Children aged less than 15 years and pregnant women were excluded.ResultsA total of 168 CHIKV patients were compared with 168 DENV patients. Factors associated with CHIKV were living in poor neighborhoods (82% vs 44%; odds ratio [OR], 5.81; 95% confidence interval [CI], 3.35–10.2), having a precarious status (54% vs 33%; OR, 2.37; 95% CI, 1.49–3.78), and being born abroad (70% vs 35%; OR, 4.35; 95% CI, 2.69–7.06).ConclusionsThe present results suggest that early in the epidemic, the populations most at risk for CHIKV infection were the most socially vulnerable populations in the poorest neighborhoods, whereas DENV appeared to have affected a richer population and richer areas.

Key components of COPI and COPII machineries are required for chikungunya virus replication

The infection of CHIKV is associated with cellular membranes; however whether early secretory pathways are involved in CHIKV replication remains unclear. In the present study, we have provided initial evidences that CHIKV requires both COPI and COPII for its replication. Small interfering RNAs against COPI components, including coatomer, ARFs or GBF1, suppress CHIKV replication. Moreover, CHIKV infection is abolished by the presence of ARF1 inhibitor brefeldin A or GBF1 inhibitor golgicide A. In addition, perturbation of COPII by silencing key components of COPII pathways leads to a reduction in CHIKV replication. Collectively, these observations demonstrate the importance of functional secretory pathways in the infectivity of CHIKV.

Regulatory T cells and IL-10 as modulators of chikungunya disease outcome: a preliminary study.

Regulatory T (Treg) cells hold centre stage in regulating the immune responses in most viral infections. However, their involvement in chikungunya infection is unexplored. In the current study, the frequencies and functionality of peripheral Treg and T effector (Teff) cells were assessed during different phases of chikungunya by flow cytometry and in-vitro cytokine assays. Treg cells were also studied in rheumatoid arthritis (RA) patients, whose symptoms closely mimic chronic chikungunya arthritis patients. Frequency of Treg cells was lower in acute and chronic chikungunya arthritis patients than in recovered individuals and controls, and comparable among recovered individuals and controls. Treg/Teff ratio was lower in acute than in chronic chikungunya arthritis patients, recovered individuals and controls. Higher secretion of CHIKV specific IL-10 was observed in recovered individuals than in acute, chronic chikungunya arthritis patients and controls. Frequencies of Treg and Teff cells were higher and Treg/Teff ratio was lower in RA patients than in chronic chikungunya arthritis patients. The results indicate that reduction of Treg cells was associated with ongoing CHIKV infection and normalization of Treg cells with resolution of disease. Contrasting phenotypic data in RA and chronic chikungunya arthritis suggest an altogether different mechanism of Treg-mediated pathology in both arthritis conditions. Overall, our preliminary study, suggesting an association of peripheral Treg cells and IL-10 with recovery from chikungunya, may provide insight into chikungunya disease prognosis and warrants further study.

Chikungunya virus infection in Cynomolgus macaques following Intradermal and aerosol exposure

BackgroundChikungunya virus (CHIKV) is transmitted via mosquito bite and potentially by aerosol, causing chikungunya fever and arthritic disease in humans. There are currently no licensed vaccines or antiviral therapeutics to protect against CHIKV infection in humans. Animal models recapitulating human disease, especially for transmission by aerosol, are needed for licensure of such medical countermeasures.MethodsCynomolgus macaques (CMs) were challenged by intradermal (ID) inoculation or exposure to an aerosol containing CHIKV Ross strain at different target infectious doses (103–107 plaque forming units (PFU)). The clinical and virologic courses of disease were monitored up to 14 days post-exposure.ResultsID infection of CMs led to overt clinical disease, detectable viremia, and increased blood markers of liver damage. Animals challenged by aerosol exhibited viremia and increased liver damage biomarkers with minimal observed clinical disease. All animals survived CHIKV challenge.ConclusionsWe have described CHIKV infection in CMs following ID inoculation and, for the first time, infection by aerosol. Based on limited reported cases in the published literature, the aerosol model recapitulates the virologic findings of human infection via this route. The results of this study provide additional evidence for the potential use of CMs as a model for evaluating medical countermeasures against CHIKV.

WMel limits zika and chikungunya virus infection in a Singapore Wolbachia-introgressed Ae. aegypti strain, wMel-Sg.

BackgroundZika (ZIKV) and Chikungunya (CHIKV) viruses are emerging Aedes-borne viruses that are spreading outside their known geographic range and causing wide-scale epidemics. It has been reported that these viruses can be transmitted efficiently by Ae. aegypti. Recent studies have shown that Ae. aegypti when transinfected with certain Wolbachia strains shows a reduced replication and dissemination of dengue (DENV), Chikungunya (CHIKV), and Yellow Fever (YFV) viruses. The aim of this study was to determine whether the wMel strain of Wolbachia introgressed onto a Singapore Ae. aegypti genetic background was able to limit ZIKV and CHIKV infection in the mosquito.Methodology/Principal findingsFive to seven-day old mosquitoes either infected or uninfected with wMel Wolbachia were orally infected with a Ugandan strain of ZIKV and several outbreak strains of CHIKV. The midgut and salivary glands of each mosquito were sampled at days 6, 9 and 13 days post infectious blood meal to determine midgut infection and salivary glands dissemination rates, respectively. In general, all wild type Ae. aegypti were found to have high ZIKV and CHIKV infections in their midguts and salivary glands, across all sampling days, compared to Wolbachia infected counterparts. Median viral titre for all viruses in Wolbachia infected mosquitoes were significantly lower across all time points when compared to wild type mosquitoes. Most significantly, all but two and one of the wMel infected mosquitoes had no detectable ZIKV and CHIKV, respectively, in their salivary glands at 14 days post-infectious blood meal.ConclusionsOur results showed that wMel limits both ZIKV and CHIKV infection when introgressed into a Singapore Ae. aegypti genetic background. These results also strongly suggest that female Aedes aegypti carrying Wolbachia will have a reduced capacity to transmit ZIKV and CHIKV.

Unusual pattern of chikungunya virus epidemic in the Americas, the Panamanian experience.

BackgroundChikungunya virus (CHIKV) typically causes explosive epidemics of fever, rash and polyarthralgia after its introduction into naïve populations. Since its introduction in Panama in May of 2014, few autochthonous cases have been reported; most of them were found within limited outbreaks in Panama City in 2014 and Puerto Obaldia town, near the Caribbean border with Colombia in 2015. In order to confirm that Panama had few CHIKV cases compared with neighboring countries, we perform an epidemiological analysis of chikungunya cases reported from May 2014 to July 2015. Moreover, to understand this paucity of confirmed CHIKV cases, a vectorial analysis in the counties where these cases were reported was performed.MethodsChikungunya cases were identified at medical centers and notified to health authorities. Sera samples were analyzed at Gorgas Memorial Institute for viral RNA and CHIKV-specific antibody detection.ResultsA total of 413 suspected cases of CHIKV infections were reported, with incidence rates of 0.5 and 0.7 per 100,000 inhabitants in 2014 and 2015, respectively. During this period, 38.6% of CHIKV cases were autochthonous with rash and polyarthralgia as predominant symptoms. CHIKV and DENV incidence ratios were 1:306 and 1:34, respectively. A phylogenetic analysis of E1/E2 genomic segment indicates that the outbreak strains belong to the Asian genotype and cluster together with CHIKV isolates from other American countries during the same period. Statistical analysis of the National Vector Control program at the district level shows low and medium vector infestation level for most of the counties with CHIKV cases. This index was lower than for neighboring countries.ConclusionsPrevious training of clinical, laboratory and vector workers allowed a good caption and detection of the chikungunya cases and fast intervention. It is possible that low/medium vector infestation level could explain in part the paucity of chikungunya infections in Panama.

Blunting CHIKV infection by keeping T cells in check

Modulating the host immune response ameliorates arthritic disease in mice infected with chikungunya virus (Miner et al and Teo et al).

Clinical Manifestations Associated with Peripheral Joint Involvement in Patients with Acute Chikungunya Virus Infection.

AbstractChikungunya virus (CHIKV) causes an acute febrile illness usually accompanied by severe polyarthralgia and polyarthritis. Previous studies have shown that older age, female gender, and some comorbid conditions are associated with chronic CHIKV arthritis. However, the factors associated with acute arthralgia and arthritis are not well known. Thus, we studied the clinical manifestations associated with acute peripheral joint involvement in a group of CHIKV patients from Puerto Rico. Patients with a history of fever for < 7 days evaluated at the emergency department of a university-based hospital were tested for several pathogens including CHIKV. All patients with laboratory-positive CHIKV infection were studied. Demographic features, clinical manifestations, and comorbidities were determined. Patients with and without peripheral joint involvement were compared using bivariable and multivariable analyses. In total, 172 patients with CHIKV fever were evaluated; 52.9% were women. The mean (standard deviation) age was 21.1 years (19.3). Peripheral arthralgia and/or arthritis were seen in 156 (90.7%) patients. In the multivariable analysis adjusted for age and gender, peripheral joint involvement was associated with myalgia (odds ratio [OR] = 4.65, 95% confidence interval [CI] = 1.48-14.72), back pain (OR = 16.77, 95% CI = 3.07-313.82), ocular pain (OR = 8.88, 95% CI = 1.65-165.19), headache (OR = 3.63, 95% CI = 1.06-12.53), anorexia (OR = 5.68, 95% CI = 1.87-18.97), and nausea (OR = 6.88, 95% CI = 2.05-31.49). In conclusion, in this population of patients with acute CHIKV infection, peripheral joint involvement was associated with myalgia and back pain as well as nonmusculoskeletal manifestations such as headache, ocular pain, anorexia, and nausea.

Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations.

BackgroundChikungunya virus (CHIKV), a reemerging pathogen causes a self limited illness characterized by fever, headache, myalgia and arthralgia. However, 10–20% affected individuals develop persistent arthralgia which contributes to considerable morbidity. The exact molecular mechanisms underlying these manifestations are not well understood. The present study investigated the possible occurrence of molecular mimicry between CHIKV E1 glycoprotein and host human components.MethodologyBioinformatic tools were used to identify peptides of CHIKV E1 exhibiting similarity to host components. Two peptides (A&B) were identified using several bioinformatic tools, synthesised and used to validate the results obtained in silico. An ELISA was designed to assess the immunoreactivity of serum samples from CHIKV patients to these peptides. Further, experiments were conducted in a C57BL/6J experimental mouse model to investigate if peptide A and peptide B were indeed capable of inducing pathology.FindingsThe serum samples showed reactivity of varying degrees, indicating that these peptides are indeed being recognized by the host immune system during CHIKV infection. Further, these peptides when injected into C57BL/6J mice were able to induce significant inflammation in the muscles of C57BL/6J mice, similar to that observed in animals that were injected with CHIKV alone. Additionally, animals that were primed initially with CHIKV followed by a subsequent injection of the CHIKV peptides exhibited enhanced inflammatory pathology in the skeletal muscles as compared to animals that were injected with peptides or virus alone. Collectively these observations validate the hypothesis that molecular mimicry between CHIKV E1 protein and host proteins does contribute to pathology in CHIKV infection.