Abstract and Introduction
Abstract
In 2004, chikungunya virus (CHIKV) re-emerged from East Africa to cause devastating epidemics of debilitating and often chronic arthralgia that have affected millions of people in the Indian Ocean Basin and Asia. More limited epidemics initiated by travelers subsequently occurred in Italy and France, as well as human cases exported to most regions of the world, including the Americas where CHIKV could become endemic. Because CHIKV circulates during epidemics in an urban mosquito–human cycle, control of transmission relies on mosquito abatement, which is rarely effective. Furthermore, there is no antiviral treatment for CHIKV infection and no licensed vaccine to prevent disease. Here, we discuss the challenges to the development of a safe, effective and affordable chikungunya vaccine and recent progress toward this goal.
Introduction
Chikungunya virus (CHIKV), first isolated in 1953 during an epidemic in Tanzania among the Makonde tribe, is a mosquito-borne alphavirus in the family Togaviridae. Its name derives from a Makonde word that translates to 'disease that bends up the joints', describing the posture of infected persons experiencing severe joint pain. As described initially by Ross, CHIKV infection typically causes a "very sharp onset of crippling joint pains, severe fever and eventually the conspicuous rash". It is easily confused with dengue, and Ross described chikungunya fever (CHIK) as "a clinical variant of classical dengue differing in the absence of headache, of tenderness on pressure to the eyeballs, and of pain on eye movements". Synovitis can be severe and highly destructive, as demonstrated in a case report documenting chronic arthritis leading to destroyed metatarsal heads and osteoarthritic lesions in the ankles. However, unlike dengue, attack rates during epidemics often exceed 50% with few inapparent infections.
Although CHIK is usually self-limiting and is rarely fatal, the arthralgia is extremely painful and debilitating, typically lasting for 1 week but often much longer. For example, on La Réunion Island, 33% of joint pains, 10% of cerebral disorders and 7.5% of sensory and neural impairments among all residents were attributed to CHIKV infection during an epidemic that occurred 18 months earlier. One study in India indicated that over 72% of patients suffered from arthralgia 1 month after onset, and another estimated the mean duration of arthritic pain at 89 days. Chronic arthralgia has been associated with high levels of IL-6 and granulocyte macrophage colony-stimulating factor, and older patients and persons with high viremia during the acute phase are more likely to develop chronic symptoms. The latter study detected CHIKV in perivascular synovial macrophages in one chronic patient 18 months after onset. Both the acute arthralgia as well as the chronic disease result in major losses in productivity; in one affected region of India, approximately two-thirds of the disability measured in the population was attributed to CHIKV infections.