Chikungunya: The key role of 'innate immunity'

Blood analyses conducted during the 2007 Gabonese epidemic, studied by IRD researchers and their partners, recently showed the key role of innate immunity, the organism's first line of defence, in the clinical course of the infection. Control of the disease thus closely depends on the underlying configuration of each patient's immune system. The serious cases would therefore be due to a defect in the innate response, as happens in pregnant women, the aged, and other vulnerable groups. These investigations have brought new insights into this disease, insufficiently studied and neglected by public authorities.

Chikungunya virus, first isolated in Tanzania in 1953, caused a great number of epidemics in Africa and South-East Asia in the course of the 20^th Century.

A global threat

This infectious disease, like yellow fever and dengue, is caused by an arbovirus, transmitted by blood-sucking arthropods, ticks and Phlebotominae or sand flies. Its main vectors are mosquitoes of the genus Aedes. Particularly concerned is Aedes albopictus, nicknamed the "tiger mosquito," whose eggs enable it rapidly to conquer new territories. Increasing human travel, which spreads the larvae, and the rising resistance of mosquitoes to insecticides have contributed to the rapid expansion of epidemics over the past few years, to new regions of the world: islands in the Indian Ocean, Central Africa and even, very recently, Southern Europe are now affected. The outbreak in Réunion Island in 2005-2006 hit over 260 000 people. The recent epidemic in southern Italy, in 2007, and also the first reported case of fever in the South of France illustrate the potential for world-wide diffusion, making this disease, rarely fatal but severely incapacitating, a major threat to public health.

Strong innate immunity

Ranging from a simple bout of fever to severe pain in the joints, chikungunya can take on many different forms. This very broad variability of symptoms is due to variations in the individual immune response of each patient. IRD researchers and their partners¹ recently showed the key function of "innate immunity," the organism's first line of defence, in the clinical course of the disease.

Challenged by the presence of foreign DNA in the organism following a viral, bacterial or parasitic infection, or the presence of tumoral cells, the organism activates its immune system. This immune, or inflammatory response, occurs in two major stages: non-specific defence, also called "innate immunity," which does not take account of the nature of the micro-organism it is fighting, and the specific response, which targets the pathogenic agent in the infected cells.

In chikungunya patients, the first stage response is highly effective. Detailed analysis of nearly 70 blood plasma profiles taken during the 2007 epidemic in the Gabonese capital Libreville, revealed the presence, during the first four days of symptoms, of a high quantity of interferons, cytokines and chemokines,* immune-system substances akin to hormones- Interferons play a prime role in the immediate inflammation defence system. As the name indicates they interfere with replication of the virus in host cells and thus inhibit the virus early in the process. The function of cytokines and chemokines is to activate the second stage: the specific response. These proteins attract immune cells -leucocytes- to each virus replication site and direct the deployment of the organism's antiviral defences.

Control of the disease therefore depends closely on the underlying immune status of each patient. Severe cases could therefore be the result of a defect in the innate response mechanism, as can occur in pregnant women, elderly people or Aids patients.

A highly disabling disease

Serious forms can consequently appear, inducing highly disabling stiffening of the joints, the reason for the name of the disease: chikungunya meaning "bent man disease" in the Makonde language of Southern Africa. These symptoms generally last three to seven days, the time for the immune cells to work, but can also become chronic and persist for months, even years. Neurological and hepatic complications can also occur in the most severe forms. There is currently no specific treatment, so therapeutic care aims solely to alleviate these symptoms, using analgesic and anti-inflammatory drugs.

Medical professionals are at the dawn of their research on the disease, long neglected by government authorities. The research team is similarly exploring the role, in pathogen inhibition, of cells called Natural Killer, capable of killing directly the infected cells. In parallel, investigations are also under way on modulation of the immune response in cases of co-infection with dengue virus, recently discovered in Gabon, a new threat involving a simultaneous attack by the two severely debilitating diseases.

* Interferons, cytokines and chemokines are proteins produced by the cells of the immune system.