Zika fever is caused by an arbovirus (a virus transmitted by insects) belonging to the flavivirus genus of the Flaviviridae family, like the dengue virus and yellow fever. The insect vector of the disease, the Aedes female mosquito, can be identified thanks to the black and white markings on its legs. The species currently able to spread the Zika virus is the Aedes aegypti, which originated in Africa. Aedes albopictus (or the tiger mosquito from Asia) could also prove to be a vector of the Zika virus, as it already transmits the dengue and chikungunya viruses. (Read the news 2016/03/04: Low competence of Aedes mosquitoes for Zika virus transmission)
A mosquito becomes infected with the virus during a blood meal when it bites a person with Zika fever. The virus multiplies in the mosquito without affecting the insect. Then, when the mosquito next bites, it releases the virus into the bloodstream of another person. Symptoms appear 3 to 12 days after the bite but, during this time, the person can infect other mosquitoes if they are bitten again. This is why people suffering from Zika must avoid getting bitten to break the viral transmission cycle.
Most people infected with the virus (an estimated 70 to 80% of cases) do not develop any symptoms. In the rest of the population, the symptoms caused by the Zika virus are flu-like and include tiredness, fever (not necessarily high), headaches, and muscular and joint pain in the limbs. Different types of skin rash also feature among the symptoms. Some patients also present with conjunctivitis, pain behind the eyes, digestive problems or even swelling of the hands or feet. In most cases, the symptoms are mild and do not require hospital treatment.
As these symptoms are non-specific and the Zika virus is found in the same regions as the dengue and chikungunya viruses, it is difficult to make an accurate diagnosis.
Complications are rare but, in the event of a major outbreak, they should not be overlooked. Some cases of Guillain-Barré syndrome-type neurological complications have been observed following infection in Brazil and French Polynesia. This syndrome is characterized by progressive ascending paralysis which can affect the respiratory muscles. (Read the press release: Zika: Confirmation of a causal link between the Zika virus and Guillain-Barré Syndrome - 2016/03/01)
Pregnant women can pass on the virus to their unborn children and this can lead to serious fetal brain development defects. (Red the press release: Zika and microcephaly: first trimester of pregnancy most critical - 2016/03/16)
The Zika virus was detected for the first time in a monkey in Uganda in 1947. A year later, it was isolated in an Aedes mosquito from the same region.
The first human cases appeared in the 1970s in Africa (Uganda, Tanzania, Egypt, Central African Republic, Sierra Leone, Gabon and Senegal) and then in some countries in Asia (India, Malaysia, the Philippines, Thailand, Vietnam and Indonesia).
In 2007, an actual epidemic broke out in Micronesia (Yap Islands in the Pacific Ocean), causing 5,000 infections.
In 2013 and 2014, 55,000 cases of Zika were reported in French Polynesia. The epidemic then spread to other islands in the Pacific, namely New Caledonia, the Cook Islands and Easter Island.
The Zika virus was detected for the first time in the northwest of Brazil in May 2015 and it quickly spread to other regions of the country. Brazil has declared the highest number of Zika cases ever recorded with between 440,000 and 1,300,000 suspected cases reported.
The virus has been present in Colombia, El Salvador, Guatemala, Mexico, Panama, Paraguay, Suriname, Venezuela and Honduras since October 2015.
On December 18, 2015, two cases were detected in French Guiana by the Institut Pasteur in French Guiana. Two cases were also identified in Martinique.
On April 7, 2016, there are 16 650 compatible reported cases in Martinique (biological confirmation in progress). There are 3 620 cases in French Guiana and 1 090 in Guadeloupe.
In metropolitan France, 176 cases have been laboratory confirmed in people returning from circulation area of Zika virus, whose 7 pregnant women and 1 case of neurological complications. A person has been infected by Zika virus by sexual transmission. (Source: Invs - the French Institute for Public Health Surveillance)
The Zika virus could spread to the regions where the Aedes mosquito is already present and where people already infected with Zika are staying. In mainland France, the Aedes albopictus mosquito (tiger mosquito) is present in 30 departments of the country. In general, the vector develops in May and is active (and therefore able to transmit the virus) between May and November.
Fighting the disease
There is currently no vaccine for preventing Zika virus infection and no specific medication for treating the disease.
Treatment involves taking pain killers to relieve the painful symptoms. However, aspirin should be avoided until infection by the dengue virus has been ruled out because, in this case, the anticoagulant effect of the drug could cause bleeding.
As soon as symptoms appear, blood and urine samples are taken to confirm the diagnosis using an RT-PCR (Reverse Transcriptase-Polymerase Chain Reaction) method to detect the presence of the virus's genes.
If doubt remains after a negative result using RT-PCR, serological screening will be able to confirm whether antibodies specific to the Zika virus are present or not.
These tests are only carried out by the National Reference Centers for Arboviruses (CNRs).
The only way of protecting against the Zika disease is to protect yourself from mosquito bites both day and night, especially in the early morning and early evening when mosquitoes are most active, using physical and chemical methods — wear clothes that cover up your skin (long sleeves, pants), use suitable repellents on your clothes and areas of exposed skin, and use insecticide-impregnated mosquito nets and electric insecticide diffusers indoors.
Pregnant women living in high-risk areas must protect themselves from mosquito bites using the above methods, particularly during the first six months of pregnancy when the risk of birth defects is at its highest. Regarding repellents, they must observe the precautions for use recommended for their condition.
Pregnant women wishing to travel to areas affected by the Zika epidemic must weigh up the risks beforehand with their family physician.
As well as these personal protection measures, disease prevention also involves combating the proliferation of mosquitoes. For this, all potential mosquito breeding sites, for example stagnant water in flower pots, gutters and old tires, must be removed. It is particularly advisable to empty any water containers located around your home after each spell of rain.
At the Institut Pasteur
Institut Pasteur, with its long history of working on arborviruses, has mobilized its international forces against Zika since the very first cases. By November 2015, the Pasteur Institute of French Guiana had confirmed the first case of the virus in Suriname, and on December 18, 2015, it identified the first case in French Guiana. After confirmation of these first cases, the same team published in The Lancet the whole genome sequence of the virus responsible for this outbreak. This helped to highlight that this strain is almost the same as the strains of the epidemic that occurred in 2013 and 2014 in the Pacific. Since 2015, Institut Pasteur has been working closely with its Brazilian partners through a Tripartite Agreement signed between the Fiocruz, the University of Sao Paulo and the Institut Pasteur, with mobilized teams from its International Network to work with local task forces.
Presently, in a task force coordinated by Maria Van Kerkhove, the Institut Pasteur is mobilizing several of its research units to develop serological and molecular diagnostic tests, to work on the design of new vaccines and to provide advice on the various options to minimize vector transmission. Its teams also conduct epidemiological studies, in particular to better understand the neurological symptoms observed in patients, especially in pregnant women.
Molecular and Serologic Diagnostic tools for Zika
The Laboratory for Urgent Response to Biological Threats in Paris, led by Jean-Claude Manuguerra, is part of the WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research. It is involved in diagnosing and carrying out research into the Zika virus through the work of several of its teams :
- The Center for Viral Identification (PIV) in Paris has developed and validated a high-throughput serology technique capable of quickly diagnosing the Zika virus and other arboviruses. This technology has been distributed in the Pacific, Asia and Africa, and is currently being rolled out in South America, to tackle the outbreak. The PIV is also currently developing a simple, quick and inexpensive molecular test to save time and improve the efficacy of patient treatment.
- The Center for the Genotyping of Pathogens (PGP) in Paris has sequenced strains of the Zika virus from the epidemic in French Polynesia in 2013 and the Pacific, together with the Institut Louis Malardé in French Polynesia. In addition, the PGP is working with the Institut Pasteur in New Caledonia to sequence isolates currently circulating in the Pacific, Asia and Africa.
The Functional Genetics of Infectious Diseases unit in Paris, led by Anavaj Sakuntabhai, is working on human genetic susceptibility to Zika viral infection. Through collaboration with Amadou Sall, Institut Pasteur of Dakar, the researchers tested for the rate of antibodies of several arboviral infections among a local population. By familial genetic study, they could map a genomic region that contains gene which confers resistance to Zika viral infection. They will test candidate genes residing in the region by in vitro infection experiment. They are screening several mouse strains to identify a suitable mouse model in collaboration with the Mouse functional genetics unit.
The Institut Pasteur in French Guiana houses the National Reference Center for Arboviruses, an associated laboratory for the Antilles–French Guiana region, in the Virology Laboratory, headed by Dominique Rousset. The laboratory is therefore naturally called upon for any suspected arbovirus cases and particularly outbreaks in French territories in the Americas. This is how researchers were able to confirm the first five cases in Suriname in early November 2015 using real-time PCR. It was in December that the laboratory first detected cases of infection imported from Suriname followed, soon after, by indigenous cases.
Thanks to these samples, researchers from the Institut Pasteur in French Guiana have been able to sequence the entire genome of this virus. The findings, published in The Lancet on January 7, 2016, show that the virus which is currently circulating is very close to the one that swept through French Polynesia in 2013-2014.
- In 2014 a Zika virus outbreak in New Caledonia presented the Institut Pasteur in New Caledonia with a major influx of diagnosis requests. Researchers at the research and expertise unit for dengue and other arboviruses, headed by Myrielle Dupont-Rouzeyrol, demonstrated that the Zika virus is detected later in urine than in the blood, which may enable more effective biological diagnosis of patients (Gourinat et al., 2015). Building on these initial findings, the researchers are taking part in a project with the Scientific Institute of Public Health (Belgium), the Institut Pasteur in French Guiana and the Institut Pasteur in Paris aimed at improving diagnosis of arboviruses and Zika virus in particular, by comparing the use of urine and saliva samples with blood samples. In partnership with the Institut Pasteur in Dakar (with the involvement of the Institut Pasteur in Cambodia, the Institut Pasteur in Laos, the Institut Pasteur in Paris and Institut Louis Malardé) the unit is also coordinating a project aimed at assessing the ability of different mosquitoes to transmit the Zika virus through bites and studying the genetic diversity of the virus in Africa, Asia Pacific and the Americas.
- In a bid to share its expertise, over a four-week period at the end of 2015, the Institut Pasteur in Dakar trained teams from the University of Sao Paulo (USP) in viral isolate culture techniques, use of its mobile laboratory for field testing and molecular and biological tools for developing specific tests to diagnose the Zika virus. Following on from this, the Institut Pasteur (in Paris and the International Network) supported the establishment of the Viral Genetic Diversity Network (VGDN) which set up the "Rede Zika" task force, involving more than thirty groups within the state of Sao Paulo, in cooperation with national and international teams (Fiocruz, Unicamp, UNESP, Instituto Butantan, Adolfo Lutz, Emilio Ribas, etc.) and hospitals (Clinicas, Sao Joje do Rio Preto, Botucatu, Universitario, Unicamp etc.).
- Since March 2016, the Institut Pasteur in Madagascar is able to diagnose Zika virus in case of a possible outbreak in Madagascar. Indeed, the Virology unit, home to the National Reference Laboratory for arboviruses, has set up a molecular test to detect Zika virus. This test may be used to identify potential infected individuals.
The World Health Organization (WHO) has classified Madagascar among the vulnerable countries. Therefore, researchers from the Institut Pasteur in Madagascar in collaboration with teams from the Ministry of Public Health, are actively working on building an action plan in case of Zika emergence on the Big Island. The complementary expertise of the institute in virology, epidemiology, immunology and entomology, is a real asset for understanding the emergence of the virus and collectively prepare a response.
Epidemiology – understanding the link between Zika and neurologic outcomes
Together with the Public Health Surveillance Office in French Polynesia, French Polynesia General Hospital and the Institut Louis Malardé, the Epidemiology of Emerging Diseases Unit (UEME), Institut Pasteur in Paris, led by Arnaud Fontanet, has been working on the Zika epidemic that hit French Polynesia (October 2013 to April 2014) since January 2014.
The project, partly funded by LaBex IBEID, has confirmed the link between the Zika virus and the sharp rise in serious paralysis-type neurological symptoms, known as Guillain-Barré syndromes (GBS), observed during the Zika virus outbreak. This research also has brought together teams from the Laboratory for Urgent Response to Biological Threats (CIBU) and the Functional Genetics of Infectious Diseases Unit at the Institut Pasteur. The results have been published in The Lancet, on March 1st, 2016.
Following the alarming rise in the number of microcephaly cases, the UEME is working to describe the incidence of this congenital defect before and after the French Polynesian outbreak. It is also trying to determine whether Zika infection in women during pregnancy is the cause, ascertain the stage of pregnancy the most at risk in the event of infection and assess the likelihood of defects in babies whose mothers are thought to have contracted the virus. The researchers have proved that the risk of microcephaly is around 1% for a fetus or newborn whose mother has been infected by the Zika virus during the first trimester of pregnancy. Their findings have been published in the journal The Lancet, on March 16, 2016.
Research on the Vector
Together with the Instituto Oswaldo Cruz in Rio de Janeiro (Brazil), researchers from the Arboviruses and Insect Vectors Unit, headed by Anna-Bella Failloux, have tested the susceptibility (the ability to contract the virus) of Aedes aegypti and Aedes albopictus mosquitoes from Brazil and Florida, where these two species co-exist.
In addition, they have assessed the vectorial competence (the ability to transmit the virus) of Aedes aegypti in French Guiana, Martinique and Guadeloupe, where this is the only species present.
These populations of mosquitoes, recently collected in the field, were infected in a BSL3 laboratory with the Asian genotype Zika virus from the Institut Pasteur in New Caledonia. This virus is almost identical to the one currently circulating in Central and South America.
This current research allowed to establish the role of the Aedes aegypti and Aedes albopictus species in the dynamics of the Zika epidemic in the Americas. The results, published in PLoS Neglected Tropical Diseases, show that, while Aedes aegypti and Aedes albopictus are both capable of becoming infected and replicating the virus in their body, they are not very competent when it comes to transmitting the Zika virus through a bite. The scientists therefore believe that the rapid spread of the Zika virus in the Americas should be attributed not to the vector competence of American mosquitoes, but rather to the vast human population that is immunologically naive to the new virus and lives near a high density of mosquito vectors.
To prepare for the possible arrival of the Zika virus in France and Europe, following on from the example of chikungunya and the dengue virus (indigenous cases of chikungunya in France in 2010 and 2014, and the dengue virus in 2010, 2014 and 2015) spread by Aedes albopictus, researchers have tested two populations of Aedes aegypti from Madeira and two populations of Aedes albopictus from the South of France (Nice and Bar-sur-Loup).
These two projects were funded by the LaBex IBEID (led by Pascale Cossart and Philippe Sansonetti) and the European DENFREE project (coordinated by Anavaj Sakuntabhai).
- The team at the Medical Entomology Unit in Institut Pasteur French Guiana, headed by Romain Girod, is developing trapping systems combined with sugar baits designed for early detection of Zika virus circulation in French Guiana. The researchers are testing new entomological and virological monitoring tools both in the laboratory and the field with a view to identifying the areas and periods most conducive to virus transmission and therefore effectively guiding any preventive and vector control measures. Previous work carried out during the chikungunya outbreak that struck French Guiana in 2014-2015 has already demonstrated the potential of the tools developed. The current work on the Zika virus is a continuation of these earlier efforts.
- The Medical Entomology Laboratory at the Institut Pasteur in Guadaloupe, headed by Anubis Vega-Rua, helped assess the vectorial competence of mosquito populations from the Americas with respect to the Zika virus as part of a project coordinated by Anna-Bella Failloux at the Institut Pasteur in Paris. The laboratory also worked alongside Guadeloupe’s Regional Health Agency (ARS) on awareness campaigns highlighting the dangers of the Zika virus for the population of Guadeloupe. The laboratory and ARS are currently devising a new strategy of intervention and entomological investigation to be deployed if indigenous cases of Zika virus are detected in Guadeloupe. Besides this, the clinical biology laboratory at the Institut Pasteur in Guadeloupe performs molecular diagnosis of Zika virus infections.
- The Arbovirus Group at the Institut Pasteur in French Guiana is interested in developing animal models to shed new light on the pathological effects observed in humans. In addition, it is trying to clarify the interaction between the Zika virus and Aedes aegypti (primary vector) and Aedes albopictus (potential vector for the emergence and spread of the virus on a global scale) mosquitoes to improve understanding of the mechanisms involved in the vector-borne transmission of this virus and define new targets to block the infection of new vertebrate hosts.
VIDEO - Virus Zika, pourquoi aujourd'hui ?
Arnaud Fontanet, responsable de l’unité d’épidémiologie des maladies émergentes, co-directeur de l’école Pasteur/CNAM de Santé publique
Arnaud Fontanet nous explique dans cette vidéo les résultats obtenus avec ses collègues de Polynésie française lors de l’épidémie de Zika de 2013-2014 : les scientifiques ont établi le lien de causalité entre le virus et certains cas graves avec syndromes de Guillain-Barré d'une part, et d’autre part des cas de microcéphalie chez des enfants nés de femmes ayant été infectées au cours de leur grossesse.
VIDEO - Zika Summit 2016
Zika virus poses many questions and concerns for humanity. Scientists and experts are racing to understand the relationship between Zika virus infection and associated neurological complications such a microcephaly and Guillain-Barré syndrome.
The Institut Pasteur, WHO and other partners convened reserachers and public health experts working on this ongooing public health emergency to share preliminary results and discuss next steps.