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Home , Flaviviridae, Zika virus

#57 Focus Dengue , and the Zika

Arboviruses are a group of virus that can be southern regions of mainland France and transmitted between animals and humans, on the island of Réunion, albopictus and they are common to humans and many provides the sole vector for transmission. vertebrates (, , reptiles, Transmission amphibians). There are over 500 species of , Chikungunya and the Zika , sub-divided into approximately virus are all transmitted in the same way. 10 different families, including Togaviridae, Human to human transmission takes place

Flaviviridae, , , International and Bunyaviridae. These have RNA by vector in urban areas during with a very heterogeneous structure and are epidemics: the mosquito picks up the virus transmitted via bites from hematophagous when it bites a carrier, and then transmits it such as mosquitoes, sandflies, to a healthy person with another bite. The and mites (arbovirus is short for mosquito bites people outside their homes -borne virus). throughout the day, with peak activity at dawn and dusk. The mosquitoes live in Chikungunya urban areas and lay their eggs in pools of stagnant water (250 eggs every 2 days), This disease was first described in Tanzania where they develop into larvae. The eggs in 1952. It is caused by an arbovirus of the are resistant to the cold in winter and hatch from the Togaviridae family. when weather conditions improve. It was then also described in Africa, Southeast is spreading globally; it Asia, the Indian subcontinent and the Indian has adapted to both tropical and temperate Ocean. Finally, it was first described in Europe climates. in 2007, in Italy. Chikungunya means "to become contorted" in Clinical presentation the Kimakonde language (spoken by a tribe in There is a short , which south east Tanzania) and reflects the severity lasts an average of 47 days (1-12 days), after of the pain that can be associated with this which patients develop sudden high fever infection. of > 38.5 °C, headache, myalgia or intense, Globally, the virus is transmitted by female debilitating joint pain, potentially associated mosquitoes of the species Aedes albopictus with , maculopapular rash,

(tiger mosquito) and , but in itching, nausea, mild bleeding (gingivitis, Focus 57-INTGB - May 2018

1/6 epistaxis). It should be noted that cases can < D5: RT-PCR be asymptomatic (13% of cases on Réunion D5-D7: RT-PCR and serology during the 2007 epidemic). The acute phase D7: serology only (viremic phase during which the disease can be transmitted by a bite) lasts 5-10 days. It is Chikungunya: major outbreaks followed by fatigue, weight loss, anorexia with The first significant outbreak of the disease dysgeusia, hair loss, skin disorders (patches was reported in the Congo in 1999/2000. of dyschromia, xerosis and itching), and Since 2005, there has been an epidemic in memory impairment. Course of the disease the Indian Ocean (with cases imported to can be rapidly favourable, or recovery may Europe); in 2007 there was an outbreak in the be slow and marked by significant asthenia. north east of Italy, and in late 2013-2014 there Relapses affecting the joints, with or without was a major epidemic in the West Indies and fever, can occur (but the patient is not Guyana and, in 2014 there were cases in the contagious). In 30-60% of cases, the disease south east of France and in Corsica. progresses to a chronic phase characterised Dengue Fever by persistent arthralgia and partial disability; this phase can last from a few weeks to This disease is caused by the dengue several months. Some complications have virus, an arbovirus also transmitted by been observed, such as high fever, extensive mosquitoes of the Aedes genus. The virus vesiculobullous lesions, and involvement belongs to the genus in the of the brain (meningoencephalitis), liver family . (), kidneys (acute renal failure), or Cases of dengue fever appear to be on the the heart (myocarditis). One possible case rise. There are 4 known serotypes (D1 to of mother-to-child transmission has been D4), and they do not provide crossimmunity described on Réunion. (it is possible for one person to have 4 The mortality rate is 3.6 per thousand. Patients infections in their lifetime). have lasting immunity once recovered. There Serotypes 1, 2, and 3 are more prevalent is no treatment or available. in Asia and the West Indies/Guyana, and serotypes 1 and 2 are more common in Africa. Biological diagnosis The 1977-78 epidemic in the Indian Ocean The test to be performed depends on when (Réunion) was caused by serotype 2, and the the sample is taken in relation to the date on 2004 and 2010 epidemics were caused by which symptoms first appeared (see Fig. 1): serotype 1 and serotype 3 respectively.

Fig. 1: Sequence of the appearance of biological markers

IgM IgG

D-7 D-2 0 D5 D7-D10 D30 3-6 months

Culture, PCR Focus 57-INTGB - May 2018

2/6 Epidemiology from Dengue 1 followed by Dengue 2). The Dengue fever is hyperendemic in the West warning signs for complications (or serious Indies and Guyana, as well as in South forms of dengue fever) are abdominal pain, America and some countries in Africa persistent vomiting, oedema, bleeding and Asia. It has also emerged in French mucosa, lethargy or agitation, hepatomegaly, territories in the Pacific Ocean and in the thrombocytopenia and increased haematocrit south east of mainland France. levels. 2010 in the French departments of Biological diagnosis Alpes-Maritimes and Var: 2 cases of Diagnosis of the primary infection is based local transmission of dengue fever (+2 on the detection of the viral by RT- cases of Chikungunya) PCR ( if carried out within the 7 first days) 2013 in the Bouches du Rhône and/or by IgM and IgG serology ( from the department: 1 case of local fifth day of infection) transmission of dengue fever The serology should be interpreted on two 2014: 4 confirmed cases of local samples, one of which must be drawn ≥15 transmission of dengue fever: 2 in the d. This is due to the fact that IgM tests have Bouches du Rhône and 2 in the Var of lack of specificity (false positive cases). 2015: 6 cases of local transmission of dengue fever in Languedoc Roussillon. It is important to pay attention when interpreting secondary dengue infections Clinical presentation (patients previously infected with serotype The infection is asymptomatic in 50 to 85% D1 dengue will already have IgG antibodies of cases. When symptoms do occur, they when infected with serotype D2). are extremely variable and the course of Immunity is present for a given serotype the disease is unpredictable. There is an but it does not protect from infections with incubation period of 4-10 days, after which other serotypes. onset of the disease is sudden and severe, characterised by high fever, widespread pain, Diagnostic strategy rash, fatigue, and gastrointestinal symptoms from D0 to D5: PCR only (loss of appetite, nausea, vomiting). However, from D5 to D7 inclusive: PCR and in some people the disease can take on a serology haemorrhagic form or cause dengue shock serology only syndrome. The risk of contracting a more after D7: serious form of the disease is higher in cases Testing for the NS1 antigen is only indicated where there is a higher viral load or where in regions where there is an outbreak of the a patient contracts consecutive infections disease and from D0 to D5; a negative NS1 caused by different serotypes (the highest antigen test must be confirmed by PCR and/ risk of a serious form of the disease comes or serology.

Kinetics of the virus and antibodies during infection by the Focus 57-INTGB - May 2018

3/6 Treatment This plan is active during the mosquito There is no specific treatment for dengue season from 1 May to 30 November. fever, but the symptoms can be treated. Finally, the InVs [French Institute for Public A vaccine (Dengvaxia®) was granted Health Surveillance] collects all positive marketing authorisation in December diagnoses from the laboratories performing 2015 in Mexico, the Philippines, and these analyses. (and this marketing authorisation is being In 2014: 1,490 suspected cases in 18 extended rapidly to other countries). The departments, including 446 confirmed vaccine is for the prevention of the 4 dengue cases of Chikungunya (all imported cases); fever serotypes, for use in endemic areas 166 confirmed cases of dengue fever (all only, and in people aged 9 to 45 years. imported), 6 co-infections and 4 cases of Monitoring plan local transmission of dengue fever. The plan for monitoring dengue fever is From 1 May to 27 November 2015: based on mandatory immediate reporting 127 confirmed cases of imported dengue to the ARS [French regional health fever; 30 confirmed cases of imported authorities] (if 2nd positive serum IgM test). Chikungunya; 6 confirmed cases of local transmission of dengue fever. A regional plan for enhanced monitoring has been implemented in the French The departments where the mosquito is The Zika virus is an enveloped Flavivirus established. with a singlestranded RNA genome. There are two strains of the virus: one African strain (with two substrains) and an Asian strain. It was first isolated in 1947 in a in (in the from which it takes its name), and then in humans in 1952 (Uganda, Tanzania). It has been circulating in Africa and Asia for a long time. There have been epidemics in Micronesia (2007), (2013) and (2014). Like dengue fever and Chikungunya, the vector is a mosquito of the genus Aedes. In addition to transmission by mosquito vector, there is evidence that sexual and perinatal transmission of the Zika virus is also possible, as well as transmission via . Current and recent epidemics There was an epidemic of the Zika virus in Brazil in May 2015. Enhanced surveillance was put in place in the West Indies and Guyana. In early December 2015, cases of what was presumed to be the Zika virus were described in Martinique. On 15 December 2015, the first case of Zika was confirmed in Guyana, followed by confirmation of another 10 cases, all of which were imported. On 22 December 2015, two cases of local transmission

Data from enhanced monitoring in mainland France in 2014 and 2015 Focus 57-INTGB - May 2018

4/6 were confirmed in Martinique, followed by autoimmune complications (purpura). five more in Guyana. In early 2016, the If the Zika virus is contracted during epidemic had reached Guadeloupe and , it can also cause intrauterine the northern islands. brain development abnormalities and (observed in Brazil and Clinical presentation Polynesia among the newborn babies of The infection is asymptomatic in 70-80% of mothers who were infected during the first cases. In cases that do develop symptoms or second trimester of pregnancy). there is an incubation period of 3 to 12 In patients who have recently returned days, after which patients experience from an epidemic area, the Zika virus is to flu-like symptoms and a diffuse, itchy, be suspected in those presenting with a maculopapular rash. The rash covers a maculopapular rash with or without fever, large area and spreads downwards from even moderate fever, and at least two the face to the extremities, remaining of the following symptoms: conjunctival for about 6 days, predominantly on the hyperaemia, arthralgia, myalgia, in the torso. Other symptoms include asthenia, absence of any other aetiology. fever (or temporary low-grade fever), arthralgia (lasting 3-5 days), headaches : comparison of clinical with pain chiefly behind the eyes, symptoms myalgia, and conjunctivitis. Although it (from Halstead SB et al, A J Trop Med Hyg is not immediately serious, the infection and the booklet of the Yap State Department can develop neurological complications: of Health Service) Guillain-Barré syndrome, 2-23 days after the viral infection, , meningoencephalitis, optical neuritis or

Dengue Symptoms Chikungunya

Fever ++++ +++ +++

Myalgia / arthralgia +++ ++++ ++

Maculopapular rash ++ ++ +++

Pain behind the eyes ++ + ++

Conjunctivitis 0 + +++

Enlarged lymph nodes ++ ++ +

Hepatomegaly 0 +++ 0

Leukopenia, thrombocyto- +++ +++ 0 penia

Haemorrhagic events + 0 0 Focus 57-INTGB - May 2018

5/6 Diagnostic biologique Conclusion There is currently an epidemic of Zika virus in the French West Indies. The con- ditions for an epidemic in mainland France are present, and there is a real risk from May to November. In the light of the pres- ence of transmission vectors and influx of passengers, the French Public Health Council [Haut Conseil de la Santé] has concluded that "the risk of transmission of Diagnosis is based on using RT-PCR to Zika virus detect the viral genome. is high in the French departments in In the blood: viremia is transient the Caribbean (Guyana, Guadaloupe, and viral load is low and short-lived Martinique) where the vector Ae. aegypti (0 to 7 days after the onset of clinical is present, and this risk concerns the symptoms); whole of the population residing or In saliva: the virus is present and can holidaying there; be detected for the same period of time is real in Réunion (presence of Ae. as in the blood; the value of the viral albopictus) and in Mayotte (presence of load is unknown; Ae. albopictus and Ae. aegypti), and this In urine: the virus is present up to 10 risk concerns the whole of the population days after onset of symptoms, and the residing or holidaying there; viral load is higher. is real in the departments of mainland Anti-Zika IgM and IgG serology can France where Ae. albopictus is currently be performed at the National established; this risk exists during its Reference Centre [CNR] (Marseille) with period of activity from May to November, whole virus, but there are cross-reactions particularly in the event of virus with other , and this test does circulation in the Caribbean. This risk not differentiate between dengue virus and concerns the whole of the population Zika (serology tests positive for Flavivirus; residing or holidaying there." if the neutralisation test is negative for Carole Emile, based on a statement by Véronique dengue virus, it may be positive for Zika by Jacomo, Biomnis Lyon (February 2016) default). The NRC recommends monitoring Focus 57-INTGB - May 2018 serology at 1 month.

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