Chikungunya fever is an acute febrile illness associated with severe, often debilitating polyarthralgias. The disease is caused by Chikungunya virus (CHIKV), an arthropod-borne virus that is transmitted to humans primarily via the bite of an infected mosquito. Since a re-emergence of CHIKV in 2004, the virus has spread into novel locations, such as Europe, and has led to millions of cases of disease throughout countries in and around the Indian Ocean. The risk of importation of CHIKV into new areas is ever present because of the high attack rates associated with the recurring epidemics, the high levels of viremia in infected humans, and the worldwide distribution of the vectors responsible for transmitting CHIKV. In this review, we will characterize the epidemiology and global expansion of CHIKV, describe the clinical features and laboratory testing for the disease, and discuss priorities for further studies needed for effective disease control and prevention.

Chikungunya Fever: An Epidemiological Review of a Re-Emerging Infectious Disease

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60281-X.pdf

Chikungunya: a re-emerging virus

Alphaviruses, including Chikungunya virus (CHIKV), produce a transient illness in humans, but severe forms leading to chronic incapacitating arthralgia/arthritis have been reported by mechanisms largely ill-characterized. The pathogenesis of CHIKV was addressed in a prospective cohort study of 49 hospitalized patients from Reunion Island subsequently categorized into two distinct groups at 12 mo postinfection. Comprehensive analyses of the clinical and immunological parameters throughout the disease course were analyzed in either the “recovered” or the “chronic” groups to identify prognostic markers of arthritis-like pathology after CHIKV disease. We found that the chronic group consisted mainly of more elderly patients (\textgreater60 y) and with much higher viral loads (up to 1010 viruses per milliliter of blood) during the acute phase. Remarkably, a rapid innate immune antiviral response was demonstrated by robust dendritic/NK/CD4/CD8 cell activation and accompanied by a rather weak Th1/Th2 cytokine response in both groups. Interestingly, the antiviral immune response witnessed by high levels of IFN-α mRNA in PBMCs and circulating IL-12 persisted for months only in the chronic group. CHIKV (RNA and proteins) was found in perivascular synovial macrophages in one chronic patient 18 mo postinfection surrounded by infiltrating NK and T cells (CD4++ but rare cytotoxic CD8). Fibroblast hyperplasia, strong angiogenesis, tissue lesions given the high levels of matrix metalloproteinase 2, and acute cell death [high cleaved poly(ADP-ribose) polymerase staining] were observed in the injured synovial tissue. These observed cellular and molecular events may contribute to chronic arthralgia/arthritis targeted by methotrexate used empirically for effective treatment but with immunosuppressive function in a context of viral persistence.

Persistent Chronic Inflammation and Infection by Chikungunya Arthritogenic Alphavirus in Spite of a Robust Host Immune Response

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that induces in humans a disease characterized by fever, rash, and pain in muscles and joints. The recent emergence or reemergence of CHIKV in the Indian Ocean Islands and India has stressed the need to better understand the pathogenesis of this disease. Previous CHIKV disease models have used young or immunodeficient mice, but these do not recapitulate human disease patterns and are unsuitable for testing immune-based therapies. Herein, we describe what we believe to be a new model for CHIKV infection in adult, immunocompetent cynomolgus macaques. CHIKV infection in these animals recapitulated the viral, clinical, and pathological features observed in human disease. In the macaques, long-term CHIKV infection was observed in joints, muscles, lymphoid organs, and liver, which could explain the long-lasting CHIKV disease symptoms observed in humans. In addition, the study identified macrophages as the main cellular reservoirs during the late stages of CHIKV infection in vivo. This model of CHIKV physiopathology should allow the development of new therapeutic and/or prophylactic strategies.

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Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages

Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy.

In April 2005, an outbreak of Chikungunya fever occurred on the island of Reunion in the Indian Ocean During winter 2005, six patients developed meningoencephalitis and acute hepatitis due to Chikungunya virus Our objectives were to determine the incidence and mortality of atypical Chikungunya viral infections and to identify risk factors for severe disease A hospital-based surveillance system was established to collect data on atypical Chikungunya cases Case reports, medical records and laboratory results were reviewed and analysed We defined an atypical case as one in which a patient with laboratory-confirmed Chikungunya virus infection developed symptoms other than fever and arthralgia We defined a severe atypical case as one which required maintenance of at least one vital function We recorded 610 atypical cases of Chikungunya fever: 222 were severe cases, 65 affected patients died Five hundred and forty-six cases had underlying medical conditions (of which 226 suffered from cardiovascular, 147 from neurological and 150 from respiratory disorders) Clinical features that had never been associated with Chikungunya fever were recorded, such as bullous dermatosis, pneumonia, and diabetes mellitus Hypertension, and underlying respiratory or cardiological conditions were independent risk factors for disease severity The overall mortality rate was 106% and it increased with age This is the first time that severe cases and deaths due to Chikungunya fever have been documented The information presented in this article may assist clinicians in identifying the disease, selecting the treatment strategy, and anticipating the course of illness

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0950268808001167

Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Réunion.

B. Helynck

Papers

Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Réunion.