Emergence and Clinical Insights into the Pathology of Chikungunya Virus Infection

Expert Commentary & Five-year View

As demonstrated in the recent epidemics in the Indian Ocean and Europe, it is likely that CHIKV could emerge in any tropical or temperate area where Ae. albopictus is present. A concerted set of actions will be required to tackle this problem, with community-based and governmental interventions essential for the early detection and risk reduction through implementation of aggressive vector control measures and health communications.

The validated control measures for Ae. albopictus rely on the reduction of human-to-vector contact through the use of insect repellents and on the reduction of the larval source by removing water-holding containers. The use of larvicides such as temephos and Bacillus thuringiensis israelensis applied at breeding sites have been used to limit mosquito population sizes, together with classical organophosphate insecticides to limit the density of adult mosquitoes. The cost to the environment is not negligible and alternative strategies should be encouraged with the hope that biologic control measures will be proposed in the next 5 years. These new measures are currently in trials and include the release of sterile male or genetically modified mosquitoes that are unable to transmit diseases to humans. All these measures will benefit from experimental models incorporating ecologic, entomologic and virologic factors to obtain a better knowledge of factors contributing to the spread of the disease.

From a patient's point of view, physicians will have a key role in detecting and treating new cases and taking into account the great vulnerability of pregnant mothers and newborns. These patients will be treated using polyvalent immunoglobulins or any other neutralizing polyclonal or anti-CHIKV monoclonal antibodies. Humanized monoclonal antibodies against viral envelope proteins may also be of use. Treatments should aim to treat the nature of chronic nociceptive but also neuropathic pains. Our understanding of CHIKV pathology is still in its infancy and experiments using existing and novel animal models are highly warranted to help us obtain a better understanding of the mechanisms driving arthralgias and rheumatism. Experiments addressing the interactions between the host and CHIKV are highly warranted, in particular, to explain the mechanisms of viral persistence and chronic arthritis in a non-autoimmune context. Novel noninvasive imaging techniques such as ¹⁸fluorodeoxyglucose PET combined with nuclear magnetic resonance should help us to decipher the arthritis mechanisms (bone erosion and level of fibrosis) that may be controlled by methotrexate treatment.

These studies are important in designing novel antiviral control strategies, including treatments delivered at sites of viral persistence such as IFN-α.^[57]

A live-attenuated vaccine was originally advanced through to Phase II human trials, but its development was halted because of its poor tolerance, problems of interference with other alphaviruses and a lack of demand. The study of this and other potential vaccine formulations, such as chimeric alphavirus vaccines, should be renewed. Epitope-based vaccines may provide an alternative approach as they could incorporate both T- and B-cell epitopes in a single formulation.

Expert Rev Anti Infect Ther. 2010;8(9):987-996. © 2010  Expert Reviews Ltd.