Causes
The chikungunya virus is an arbovirus (a virus transmitted by arthropods) that is spread by the female mosquitoes of the Aedes genus, that have distinctive black and white stripes, primarily from the two species Aedes aegypti and Aedes albopictus. Aedes albopictus is present in the south of France and Aedes aegypti is present in the overseas departments of France (the West Indies, Guyana) and French Polynesia (New Caledonia). These two mosquitoes can also transmit other arboviruses including dengue, yellow fever and Zika.
Symptoms
A highly debilitating infection
In the Makonde language, chikungunya means “walking bent over”, an allusion to the stooped posture of chikungunya patients crippled by painful joints.
After an incubation period of 2 to 10 days, the chikungunya virus causes severe, often debilitating joint pain in infected patients, mainly in small joints such as the wrists, fingers, ankles, and feet, but sometimes in the knees and occasionally in the hips or shoulders. Those affected also frequently suffer from headaches, fever, severe muscle pain, a rash on the torso and limbs, swelling in one or more cervical lymph nodes, and conjunctivitis.
Bleeding gums and nosebleeds have often been described in connection with the disease, mainly in Asia.
Although severe forms of chikungunya had only rarely been observed, in historically endemic areas, during the 2005 epidemic on Reunion Island severe neurological forms were reported, including cases of meningoencephalitis and damage to peripheral nerves. These complications mainly affected elderly patients, those with a weakened immune system, or newborn babies who had been infected in utero by their mothers.
Remission and long-term effects
The clinical symptoms of chikungunya usually disappear relatively quickly – patients tend to recover from the fever and rashes associated with the disease within a few days, but joint problems can persist for several weeks. Infection by the chikungunya virus does not seem to have been the direct cause of the small number of fatalities recorded during epidemics.
Joint pain can persist in subacute or chronic form for several months or even years, particularly in older patients. In a retrospective South African study, 10% of patients were still affected 3 to 5 years after acute infection by the chikungunya virus.
Epidemiology
The first epidemic caused by the chikungunya virus was recorded in Tanzania in 1952. Since then, infection by the chikungunya virus has continued to develop in endemic and epidemic form on the African and Asian continents, particularly in India since 2006 and in the Indian Ocean region. In 2007, chikungunya was also recorded in Europe for the first time, with several hundred cases in the north west of Italy in September of that year. In 2010, the first two indigenous cases of chikungunya were recorded in France, in the Var department. In 2011, New Caledonia was affected, and in December 2013 an epidemic broke out in the Caribbean, in Saint-Martin. It spread to the rest of the Caribbean and then to the American continent. Finally, French Polynesia was reached in 2014.
Europe
There is a real possibility that the chikungunya virus might spread in the warmer regions of Europe, where the Aedes albopictus mosquito vector, known as the tiger mosquito, has established itself especially in Italy and the south of France. In September 2007, an epidemic outbreak occurred in the Ravenna region of Italy, affecting some three hundred people. It is believed to have been introduced by a traveler returning from India. The first two indigenous cases of chikungunya in France were detected in 2010 in the Var department, and then in October 2014 12 other indigenous cases were observed in Montpellier. In 2017, 17 other chikungunya cases were reported in the PACA region. There is risk of dengue and chikungunya becoming endemic in southern Europe and they are therefore being followed by the public health authorities. This has led to chikungunya being added to the notifiable diseases list, and surveillance measures have been stepped up since January 2006.
Africa and Asia
The transmission area for the chikungunya virus encompasses the whole of Sub-Saharan Africa and South-East Asia. In Africa, the virus is spread via a jungle cycle involving primates and sylvatic mosquitoes (Aedes luteocephalus, Aedes furcifer, and Aedes taylori). In Asia, where the virus was introduced more recently, it circulates in a mainly urban cycle, involving the Aedes aegypti and Aedes albopictus mosquitoes.
Since it was first described in Tanzania, the chikungunya virus has regularly caused small-scale cyclical epidemic outbreaks in rural areas, mainly in southern and eastern Africa, from Uganda to South Africa, and in Central Africa. The most recent major epidemic on the African continent was in 2007 in Gabon, with 5,000 suspected cases. The chikungunya virus is occasionally seen in West Africa, particularly Senegal. It is considered as endemic in rural areas of Africa, where it is likely responsible for several undiagnosed cases.
Epidemic outbreaks have also been observed in India, Sri Lanka, South-East Asia (Thailand, Myanmar, Vietnam, Laos, Cambodia, Indonesia, and more recently Malaysia), and the Philippines. Some isolated cases were reported in Singapore in 2009. A major epidemic struck India in January 2006 and has continued to spread, with some two million suspected cases reported to date. The higher frequency of epidemics in Asia can be explained by the prevalence of mosquito vectors that are more anthropophilic (preferring humans) in these areas.
Indian Ocean
In the Indian Ocean region, no cases of chikungunya were reported before the beginning of 2005, when a first epidemic, thought to have emerged in East Africa, hit the Comoros. The virus was most likely spread by the Aedes aegypti mosquito, which is widespread in this archipelago.
In March 2005, the epidemic rapidly spread throughout Reunion Island from the north west, with a major outbreak between late April and early June. The virus continued to spread during the austral winter months. On this island, the virus was mainly transmitted by the Aedes albopictus mosquito, which is highly versatile – it can colonize both urban and sylvatic environments and use both artificial and natural breeding grounds. A total of around 270,000 people are thought to have been infected, out of a total population of 750,000. At the same time, from the end of March 2005, the Seychelles, Mauritius, and Mayotte were also affected by the chikungunya virus epidemic, with cases increasing from January 2006. In spring 2010, chikungunya struck again on Reunion Island, with around twenty confirmed cases.
America
Two cases of importation from Madagascar were identified in French Guiana in March 2006, highlighting the risk of emergence of the virus in the French territories of the Americas. In December 2013, the epidemic broke out in the Caribbean in Saint-Martin and grew rapidly. Martinique and Guadeloupe were heavily impacted and the epidemic spread throughout the Caribbean, finally reaching the American continent for the first time, where it also caused a serious epidemic.
Treatment and prevention
Medical treatment for chikungunya is purely symptomatic and is based on painkillers and anti-inflammatory drugs. But these treatments are unable to prevent chronic progression of the disease. Corticosteroid treatment may be necessary for patients who develop subacute or chronic symptoms.
The prevention of chikungunya involves individual and collective efforts to improve vector control. Individuals can limit their exposure to the mosquito vector by wearing long clothes, applying insect repellant and treating clothes with insecticides, and using mosquito nets. Larger-scale vector control involves pre-emptive spraying with insecticides and removing potential breeding grounds, particularly around living areas (flower pots and other containers, used tires, bulky waste, etc.).
“The Geopolitics of the Mosquito” - Go further with our experts!
At the Institut Pasteur
The Institut Pasteur’s response to the threat of chikungunya in 2005 is a prime example of the swift, effective action of its scientists. The Institut Pasteur in Paris launched a vast research program on the chikungunya virus involving a dozen teams coordinated by Felix Rey, Head of the Virology Department. They developed diagnostic tests in record time, traced the evolutionary history of the virus, sequenced the genomes of several viral strains, and identified the origins of the epidemic. The scientists also developed an animal model of the disease, designed a vaccine candidate, and identified the human cells targeted by the virus and the genes capable of controlling infection. Other research pinpointed the virulence factors of the virus and shed light on the transmission methods used by Aedes albopictus.
Today, around ten teams are still focusing their research on chikungunya. The Environment and Infectious Risks Unit continued the KerARBO project, notably by developing a model for monitoring infection by the Alphaviruses RossRiver and Chikungunya using intravital imaging with viruses containing reporter genes. This study allowed to follow the infection until its passage to chronicity and suggests that the virus could persist locally in the joint cells. This innovative approach opens the way to the evaluation of new therapeutic or vaccine strategies.
A candidate vaccine against the chikungunya virus was developed by the Viral Genomics and Immunization Unit, headed by Frédéric Tangy. It is a vector derived from the measles vaccine expressing a chikungunya virus antigen. A Phase I clinical trial in 2014 demonstrated the safety and immunogenicity of the vaccine candidate in humans1. A Phase II clinical trial was then conducted by Themis, which confirmed the safety and immunogenicity of the candidate vaccine on a larger scale, despite the presence of pre-immunity to measles in all volunteers2. The vaccine is now expected to enter a Phase III efficacy trial.
Anna-Bella Failloux and her Arbovirus and Insects Vectors unit study the ability of mosquitoes to transmit the virus responsible for chikungunya disease to humans. Since the beginning of the 2005 epidemic, the team has obtained research results that enable a better understanding of the extent of the outbreak. In particular, the team determined that the time it takes for the virus to travel between infection with virus in a patient and its presence in the salivary glands of the mosquito ready to be released is very short: about 2 days. This result forms the basis for the development of strategies to control the tiger mosquito. This group also demonstrated that the tiger mosquito could be infected with the chikungunya virus and the dengue virus at the same time and transmit these two viruses simultaneously during a sting.
Recently, several Institut Pasteur teams, coordinated by Antoine Gessain, have joined forces in the DEVA Transversal Research Program, which has led to the development of a molecular diagnostic tool for chikungunya, dengue, and West Nile virus at the Institut Pasteur’s Paris campus. The tool uses a DNA microarray to analyze serum or blood samples and diagnose acute viral infection. The microarray can also characterize the genome of the virus or viruses in the infected test sample.
1 Ramsauer et al., Lancet Inf. Dis. 2015
2 Reisinger et al., Lancet 2018
August 2021
The Institut Pasteur teams mobilized on chikungunya
Research units
> Environment and Infectious Risks Unit
Led by Jean-Claude Manuguerra
> Arboviruses and Insect Vectors Laboratory
led by Anna-Bella Failloux
> Viral Populations and Pathogenesis Group
led by Marco Vignuzzi
>Evolutionary genomics of RNA viruses
led by Etienne Simon-Lorière
