No 6 - 2012
Selected vector-borne viral diseases
Selected vector-borne viral diseases
The Department of Epidemiology receives numerous enquiries by phone and in writing concerning the risk of vector-borne disease in travellers. This issue describes selected vector-borne viral infections and includes a vaccination risk assessment, where possible. The diseases do not transfer from person to person; infection requires a competent vector. Apart from dengue fever, diagnostics are not discussed; please see previous editions of EPI-NEWS for further information. The latest vaccination recommendations are presented in EPI-NEWS 25/11 and www.ssi.dk/rejser, where you will also find information on any ongoing outbreaks (Danish language).
Mosquito bite prevention
Primary prevention including mosquito repellent, mosquito nets and clothing which covers the skin are important and markedly reduce the risk, Table 1. In Denmark, mosquito repellent of the "Autan" brand is available, the active component of which is Icaridin. In nearly all other countries, "DEET" (diethyl toluamide) is available. At a concentration of 35-50%, this product is very effective in adults. However, new data show no substantial difference between the efficacy of DEET and Autan.
Japanese Encephalitis (JE)
JE is caused by infection with a flavivirus. More than 99% of all infections are subclinical. The incubation period ranges from four to 21 days, most frequently seven days. The initial symptoms include lethargy, fever, headache, abdominal pain, nausea and vomiting. The lethargy progresses over a period of days and may be followed by restlessness, agitation, impaired motor function and progressive, impaired consciousness and coma. Clinical infection is associated with a 25% mortality.
The infection is transmitted by certain Culex mosquitoes, some of which bite during the day, Table 1. The disease is a zoonosis, and pigs and some wading birds are the reservoir. Virus is transmitted via mosquitoes to humans. Rice paddies provide optimal conditions for mosquito reproduction, and therefore the risk is higher in rural areas.
JE is found exclusively in Asia, particularly India, China and South-East Asia. It is estimated that Asia sees a minimum of 50,000 annual cases entailing up to 10,000 deaths. In Thailand and Vietnam, the disease occurs five times more frequently in the rainy season from May to October than during the rest of the year. The disease rarely affects travellers. In countries which have good vaccination programmes and therefore few human cases, e.g. Japan, the risk for travellers remains unchanged due to the zoonotic reservoir.
Primary mosquito bite prevention should always be recommended. The recommendation concerning JE vaccination in connection with stays lasting four or more weeks in the transmission zone during the risk period is not strict. Stays in rural areas with swine farming and wading birds are associated with an increased risk. Stays in urban areas will normally carry only a limited risk. In case of intense exposure or knowledge of ongoing outbreaks, stays shorter than four weeks may justify vaccination. Examples of intense exposure include prolonged stays outdoor in rural areas, particularly in the evening and night, and outdoor activities such as camping, hiking and trekking. Ongoing outbreaks, risk areas and any seasonal variation are presented at www.ssi.dk/rejser (Danish language).
The primary vaccination series consists of two vaccines which should be given at a four-week interval, EPI-NEWS 37/10. In cases of re-exposure, a booster dose of Ixiaro® is recommended 12-24 months after the primary series. In cases of continuous exposure, however, the booster dose should be given 12 months after the primary series. The duration of protection following the booster dose is unknown, but there is no evidence to suggest that duration is shorter than the three-year coverage provided by previous JE vaccines.
West Nile Virus (WNV) fever
WNV is a flavivirus closely related to JE virus. Infection caused by WNV occurs during summer and early autumn and remains asymptomatic in 80% of cases. After a 3-14 day incubation period, clinical cases present with general malaise, fever and headache. Symptoms usually last 3-6 days. In less than 1% of cases, neuroinvasive disease develops, often meningoencephalitis. This condition occurs especially in elderly and in immunosuppressed patients.
The infection is transmitted via mosquito bites, primarily by Culex species, Table 1. The Culex mosquito can survive the winter and may thus contribute in maintaining a pool of WNV for the next season. Birds are a virus reservoir and the risk is greater in rural areas. A limited number of persons have been infected via infected via blood products and organ transplants.
WNV is common in Africa, the Middle East, North America and Western Asia, EPI-NEWS 4/03. Cases of WNV are occasionally seen in Europe, EPI-NEWS 34/10, and the disease is monitored by the EU, but is not notifiable in Denmark. In the 2011 season, cases were observed in Greece, Italy, Romania, Macedonia, Albania and Turkey, EPI-NEWS 35b/11.
There is no vaccine against WNV. Primary mosquito bite prevention is recommended in connection with stays in endemic areas.
Yellow fever is caused by infection with a flavivirus. The incubation period is 3-6 days. The infection can be mild and transient, or serious with sudden symptom onset in the form of fever, chills, headache, myalgia and nausea and vomiting. The majority of patients recover, but approx. 15% relapse and develop jaundice. In particularly severe cases, kidney damage and bleeding disturbances occur. Among cases of relapse, mortality is 20-50%.
The disease is transmitted via the Aedes aegypti mosquito, which bites during the day, mainly in the early morning hours and before sunset, Table 1.
Yellow fever occurs in many parts of Africa and South America in a belt stretching from 15° north to 15° south. More than 90% of all cases occur in West Africa. Worldwide, more than 200,000 cases are detected annually, of which approx. 30,000 are fatal. In Europe, yellow fever in travellers is seen in less than one person annually and only in unvaccinated persons. Risk of yellow fever may also be present in countries with well-vaccinated populations and a history of many outbreak-free years, as the disease is a zoonosis which has primates as its reservoir and may therefore be transmitted via mosquitoes to unprotected persons.
Prevention and vaccination
Yellow fever vaccination is recommended for travels to areas where yellow fever is endemic. Effective mosquito bite prophylaxis is important despite vaccination. According to international regulations (International Health Regulations 2005), national authorities may require that travellers are vaccinated, mainly in connection with travel from a yellow fever endemic country to either a yellow fewer endemic or non-endemic country. The requirement may also cover transit stays in endemic countries and travels from a non-endemic country, e.g. Denmark. Any physician entitled to practice medicine can obtain the National Board of Health's authorization to vaccinate against yellow fever. The international certificate of vaccination is valid from ten days to ten years after vaccination. The vaccine contains live, attenuated virus, and persons with an impaired immune response, pregnant women and children >9 months should not be vaccinated unless extraordinary circumstances apply.
If a pregnant women travels to a high-risk area, vaccination should be considered. Children: See EPI-NEWS 6/11. According to the SPC, the indication for vaccination of persons above 60 years of age should be considered thoroughly as they have an increased occurrence of the rare conditions ”Yellow Fever Vaccine-Associated Neurologic Disease” (YEL-AND) and ”Yellow Fever Vaccine-Associated Viscerotropic Disease” (YEL-AVD). The incidence of YEL-AND and YEL-AVD is approx. 1-2 per 100,000 vaccinated cases > 60 years, and the diseases are almost exclusively seen in persons who have received the initial vaccination rather than in re-vacinees. If vaccination is not performed due to any of the above circumstances, and the affected person nevertheless intends to travel, the traveller should be given a certificate of exemption explaining why he or she was not vaccinated.
Dengue fever virus belongs to the flavivirus group. Four types exist and infection with one type provides life-long immunity to this type only. The incubation period ranges from three to 14 days, typically 3-7 days. The symptoms are high fever, rash, head-ache and myalgia-resembling severe influenza. However, the majority of infections are asymptomatic or cause only a mild fever. Renewed infection with another serotype may, especially in children in endemic areas, entail an increased risk of haemorrhagic dengue fever, which is a severe and potentially lethal condition with high fever and bleeding tendencies. However, primary infection may also rarely lead to haemorrhagic dengue fever, EPI-NEWS 17/08 (pdf).
The mosquito species Aedes aegypti is the primary vector and is common in the tropics and subtropics. In the recent years, Aedes albopictus (Asian tiger mosquito) which is considered a less effective vector, has increasingly been observed in the European Mediterranean countries. It bites throughout the day, but is more active in the early morning hours and in the late afternoon before sunset, Table 1. The bite is painless, but itchy. The mosquito reproduces in small pools of stagnant water (empty cans, car tyres, etc), abundant in urban areas, particularly in slum. The high population density of cities combined with the mosquitoes' daytime activity contributes to a high transmission level.
The incidence of dengue fever has increased over the latest decades and the disease is endemic to more than 100 countries, primarily in the tropics and subtropics, see www.ssi.dk/rejser (Danish language) for a detailed prevalence map. It is estimated that 50 million are infected annually, including 500,000 (1%) with severe disease resulting in 22,000 deaths. The risk of infection is higher for the local population in the endemic areas than for travellers. Nonetheless, dengue virus infection is regularly imported to Europe. Barring malaria, dengue fever is the most frequent cause of travel-associated vector-borne disease in Europe. In Denmark, the incidence is estimated at 4.9/100,000 travellers. 2010 saw the first European non-travel-associated cases of dengue since a Greek dengue epidemic in 1927-28 as two cases were detected in France and two in Croatia. The combination of frequent imported cases and the presence of a competent vector creates a risk of out-breaks in Southern Europe.
Currently, no vaccination against the disease has been registered. Use of mosquito repellent, particularly in the early morning hours and in the late afternoon, is recommended for stays in dengue endemic areas.
Dengue fever detected in Denmark
The SSI Department of Virology is the national reference laboratory for the diagnosis of exotic virus infections and performs by far the majority of dengue virus diagnostics in Denmark. Detection of IgM (and possibly IgG) in a blood sample indicates current dengue virus infection, but may be absent in the early stages of the disease. In such cases, diagnosis may be detected via viral RNA with RT-PCR or antibody titre increase in follow-up tests. However, antibodies against other flaviviruses may cause an unspecific reaction in serologic tests. Viral RNA can typically be detected during the initial days with fever, but in exceptional cases also up to 11 days after returning from an endemic area. The 2001-2009 period saw 16-46 annual cases of probable or confirmed imported dengue virus infection. All patients (aged 6-79 years) had a relevant travel history. Dengue virus infection is imported from popular tourist destinations; the majority of cases in Danes are observed in persons returning from South-East Asia, primarily Thailand, but cases also derive from South Asia, Central and South America, the Caribbean Islands and Africa. In a number of countries (e.g. Thailand and Indonesia), transmission of several circulating serotypes is seen. The trend among Danes is to travel more and more to tropical destinations. Based on statistics detailing the travel activity to endemic areas, it is estimated that approx. one case is imported for every 20,400 travellers. However, this figure is probably much higher due to under-reporting of infections with mild symptoms and infections that have receded before the patient returns, and because dengue virus infection is not notifiable in Denmark.
(L. Vinner, Department of Virology)
Chikungunya virus is an alpha virus of the togaviridae family. Infection caused by chikungunya virus presents after an incubation period of 2-12 days. The proportion of subclinical infections is unknown. Symptoms of chikungunya fever include general malaise, fever and arthralgia. Chikungunya is Maconde (a local Tanzanian language) for "he who bends" and describes the huddled up body posture caused by the intense arthralgia which normally accompanies acute infection. Symptoms last from a few days to a few weeks. Prolonged fatigue and arthralgia have been described. Infection yields life-long immunity.
The main vector transferring the virus is the Aedes aegypti mosquito, see description under dengue fever.
Chikungunya virus occurs endemically in Africa, Asia and on the Indian subcontinent, but also gives rise to outbreaks on a regular basis. 1999-2000 saw a major outbreak in the Democratic Republic of Congo, and in 2005-6 a very large outbreak occurred in the Indian Ocean countries, EPI-NEWS 33/06 (pdf). A map of areas with risk of chikungunya virus is available at:
In 2007, the transmission of chikungunya virus was reported for the first time ever in Europe in connection with a local outbreak in North-East Italy, where the primary vector was Aedes albopictus, EPI-NEWS 36/07 (pdf).
No vaccine exists against chikungunya virus infection. Prevention consists in limiting mosquito bites by using a mosquito repellent during stays in endemic areas.
Tick-borne Encephalitis (TBE)
TBE is caused by infection with a flavivirus. The incubation period is 7-14 days and symptoms are influenza-like disease lasting a few days. After a symptom-free period lasting from a few days to three weeks, approximately a third of the clinical cases develop lymphocytic meningitis or meningoencephalitis. A limited number of patients may suffer permanent or neurological sequelae of varying severity. The elderly are more prone to neurological damage. The mortality rate is 1-2%. TBE rarely takes a serious course in children below school age.
Infection of the European subtype is transmitted by the tick Ixodes ricinus, Table 1, the habitat of which is woods and grass-covered areas. Deer, mice and certain domestic animals, e.g. cats, serve as a reservoir, and transmission occurs within minutes after a tick bite.
In Scandinavia TBE is found primarily in Sweden, particularly in the area surrounding Stockholm, the coast to the south hereof and some areas around the lakes of Vänern and Vättern. In Sweden, the 2003-7-period saw an average 150 annual TBE cases. In the 2007-10-period, an average of 197 annual cases were detected. TBE also occurs in the Baltics, Russia, Siberia, on the Balkan Peninsula and in some areas of Germany and Austria. In the 2004-7-period, the incidence on the Baltic Peninsula was 6.2-13.5/100,000. Austria has previously had a high TBE incidence, but following extensive vaccination of the Austrian population, the incidence has decreased, in the 2003-7 period to 0.82/100,000. However, the risk for travellers is greater as the disease is a zoonosis. A TBE prevalence map is available at www.ssi.dk/rejser (Danish language). In Denmark, the primary risk area is the island of Bornholm. In 2010 a total of 12 TBE cases were detected on Bornholm, of whom four were infected on Bornholm, while the remaining eight cases were presumably infected abroad, EPI-NEWS 14/11. In 2008 and 2009, a total of two cases were diagnosed in Tokkekøb Hegn in North Zealand, furthermore, virus was detected in ticks from the area, EPI-NEWS 35/09 (pdf). Subsequently, no further human cases have been diagnosed in this area. In 2011, SSI diagnosed three TBE cases, presumably infected on Bornholm, Sweden and Lithuania.
The risk of tick bites can be reduced by using boots and long trousers and through frequent inspections and by brushing off the ticks. There is no evidence that the use of mosquito repellents has any effect. Vaccination may be considered in case of prolonged or repeated stays in TBE endemic areas where the behaviour in question carries a high risk, e.g. forest work, or in cases in which the wood serves as the fixed location for play, sports (e.g. orienteering) or leisure activities. Vaccination may also be considered in persons who are living permanently or have a fixed summer residence in TBE areas and who regularly leave the paths of woods and scrubland. A total of three doses are given at a recommended interval of 1-3 months between the first and second dose. In cases where there is a need to achieve a rapid immune response, the second dose may be given two weeks after the first dose. The third dose is a booster, which should be given 5-12 months after the second vaccination. To achieve immunity before the tick season starts, the first and second dose should preferably be given during the winter months and the third dose before the next season starts. Revaccination should be given at 3-5 year intervals, see the vaccine’s summary of product characteristics at www.ssi.dk
(P.H. Andersen, on behalf of the consultancy team, Department of Epidemiology)
8 February 2012