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Editors

AnuKantele
HeliSiikamäki

Viral Diseases in Warm Climates

Essentials

  • General practitioners in countries with temperate or cold climates need to know about the viral diseases discussed in this article most likely when providing advice to or treating travellers, or when working in warm climates.
  • Advice on vaccines for yellow fever and Japanese encephalitis should be given for those travelling to endemic regions.
  • Protection from mosquitos is important. Several of the viruses described below are transmitted through mosquitos.
  • Pregnant women should avoid travelling to areas endemic for zika virus.
  • The epidemiological situation of several viral diseases changes constantly. See official sources for current situation.

Haemorrhagic fevers transmitted between humans

  • Diseases include Crimean-Congo haemorrhagic fever, Lassa fever, Ebola fever and Marburg disease.
  • For more information and current epidemiological situation, see the European Centre for Disease Prevention and Control (ECDC) website http://www.ecdc.europa.eu/en/viral-haemorrhagic-fevers.

Causative agents

  • Viruses carrying the names of the diseases

Epidemiology

  • Crimean-Congo haemorrhagic fever occurs in a wide area in Eastern Europe, Central and Western Asia and Africa.
  • Lassa fever is endemic in parts of West Africa (Benin, Ghana, Guinea, Liberia, Mali, Nigeria, Sierra Leone). A more widespread than normal epidemic was reported in Nigeria in 2018.
  • Ebola fever has emerged as limited epidemics in Central and Eastern Africa, for instance in Sudan and Zaire as well as in Uganda and Republic of the Congo. An Ebola outbreak of about 30,000 infections started in Guinea in West Africa in 2014 and spread first to Liberia and then further to Sierra Leone. Infections were also detected in Nigeria, Senegal and Mali. It took 2 years and active international effort to resolve the situation. Some sporadic cases also spread to Western countries. Some sporadic cases spread also to Western countries. Since August 2018, Ebola epidemics have occurred in north-eastern parts of the Democratic Republic of the Congo. Ebola cases were found in Guinea in 2021.
  • The first outbreaks of Marburg disease occurred in Marburg and Belgrade in 1967 caused by a virus brought in with monkeys. In 1998-2000 there was an epidemic in the Democratic Republic of Congo (former Zaire) and in 2004-5 in Angola. In both the Netherlands and the United States, one case of Marburg disease infection originating in Uganda was diagnosed in 2008.

Route of infection

  • These viruses may be transmitted from person to person through close contact with the blood or secretions of an infected person.
  • The Congo-Crimean virus is carried by many domestic and wild animals, ticks serving as the vector.
  • The Lassa virus is carried by rats. Infection is transmitted by dust or foodstuffs contaminated by rat urine or by an infected person's excretions.
  • The host of the Ebola virus is not known.
  • The Marburg virus is apparently carried by monkeys.

Global significance

  • Because of its contagiousness and high fatality rate the Ebola virus has previously aroused great attention in the media during local epidemics. The Ebola outbreak that started in West Africa in 2014 was the most extensive encountered so far as regards geography, morbidity and mortality.

Symptoms

  • Haemorrhagic fever should be suspected if a patient has fever of unknown origin and/or an unexplained bleeding tendency and one of the following is known to have occurred within the last 3 weeks:
    • tick bite in an area where Crimean-Congo haemorrhagic fever is known to occur
    • close contact with a person with verified haemorrhagic fever
    • blood contact with a laboratory sample taken from a patient with haemorrhagic fever
    • contact with an animal with haemorrhagic fever
    • working in health care in an area where haemorrhagic fever occurs.

Diagnosis

  • Clinical picture
  • Viral culture, antibodies, PCR analysis (require a special safety laboratory)

Treatment

Prognosis

  • The case fatality rate of the Crimean-Congo haemorrhagic fever is 10-15%.
  • Lassa fever is usually a mild disease with low-level fever, malaise and headache. The mortality is about 1%, in patients requiring hospital treatment 15-30%.
  • Ebola fever and Marburg disease have a case fatality rate in the range of several tens of per cent.

Prevention

  • Avoiding areas with epidemics
  • Avoiding contact with blood and excretions

Dengue

Causative agent

  • A flavivirus (arbovirus), 4 different serotypes

Epidemiology

  • Dengue occurs widely in tropical and subtropical regions, mainly in urban and other residential areas (see http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf).
  • The vector mosquito is also found in Europe. An epidemic of about 2,000 cases broke out on Madeira in 2012-2013. Later on, several sporadic endemic infections have been reported in Southern Europe.

Route of infection

  • The infection is transmitted from person to person by mosquitos (Aedes aegypti as the most significant vector, Aedes albopictus also possible; both bite in the daytime, especially in towns).
  • Resistance of mosquitos to many repellents has been reported in Asia.

Global significance

  • More than a half of world population live in regions endemic for dengue.
  • Large epidemics occur occasionally. The incidence is increasing globally due to population growth and urbanization.
  • Approximately 300-400 million cases/year, and approximately 500,000 of these are serious infections, of which even 2.5% are fatal.

Symptoms

  • Incubation period is short, 4-10 days.
  • Symptoms
    • High fever (often biphasic)
    • Headache, pain behind the eyes, severe myalgia and arthralgia, nausea, respiratory symptoms, enlarged lymph nodes
    • Flushing of the face and anterior neck; 3-5 days after the onset of symptoms a weak erythematous rash appears spreading from the trunk to the face and extremities.
  • Laboratory findings
    • Leucopenia and thrombocytopenia are common in the initial phase of the disease; liver enzyme concentrations increase at the end of the first week.
  • Symptoms resolve in 2 weeks, often followed by weeks of fatigue and depression

Severe dengue

  • Probably based on an immunological mechanism
  • Caused by increased permeability of blood vessel walls which leads to plasma leakage
  • Begins like the ordinary dengue fever. After the fever has subsided at the end of the first week severe abdominal pains, prolonged vomiting, increased respiratory rate and haemorrhagic symptoms develop.
  • The risk is higher if a person who has had a dengue infection contracts an infection by another dengue serotype. The risk also depends on the characteristics of the virus and of the host.

Diagnosis

  • NS1 antigen test (positive during the first days of illness); antibody determination (antibodies are detectable after one week from symptom onset at the latest). A combination of both these tests is recommended and it provides the diagnosis in > 95% of patients with dengue.
  • If a patient returns from a region endemic for both zika virus and dengue virus, both infections can be investigated with a combined test that detects both dengue virus antibodies and antigen as well as zika virus antibodies.
  • Remember exclusion of malaria.

Treatment Corticosteroids for Dengue Infection

  • No specific treatment; careful monitoring and correction of fluid balance
  • NSAIDs should be avoided; paracetamol for fever
  • Patients with severe dengue require intensive care.

Prognosis

  • Good; mortality is under 1% in ordinary dengue.
  • In severe dengue mortality is about 20% without treatment; in hospital care the mortality can be lowered to below 1%.
  • Overcoming dengue leaves the patient with life-long immunity against viruses of the same serotype. Cross-protective immunity against other serotypes, however, remains short-lived and transient.

Prevention

  • Prevention of mosquito bites in the daytime (clothing, mosquito repellents)
  • No vaccine for travellers exists for the moment.
  • A history of dengue fever is not an obstacle for a person to travel to endemic areas. The importance of protection against mosquitos should be emphasized.

Chikungunya fever

Causative agent

  • An alphavirus (arbovirus)

Epidemiology

  • Previously endemic in parts of Africa and in South and Southeast Asia
  • In 2013, a widespread epidemic started in the Caribbean. Later on, it spread elsewhere in Middle and South America, and after that the disease has been found in both Middle and South America. From time to time, there are geographically limited epidemics in North America.
  • In 2007, chikungunya spread for the first time into temperate climate zones as a local epidemic broke out in northern Italy affecting more than 200 people, triggered by the disease in a traveller who had been infected in India. Later on, there have been sporadic local infections in Europe.
  • Several cases of chikungunya in travellers are detected each year in many European countries. Additionally, sporadic endemic cases have been reported in France and Spain, among others.

Route of infection

  • Transmitted by mosquitos. The vectors for the disease are the Aedes aegypti and the Aedes albopictus mosquitos that are active in the daytime. The latter is also found in Southern Europe.

Global significance

  • May cause wide-spread epidemics.

Symptoms

  • The incubation period is 3-7 days.
  • Symptoms are often absent or only mild.
  • High fever, rash, severe arthralgias, myalgia, headache, nausea, fatigue
  • Arthralgia may make walking difficult.
  • Haemorrhagic symptoms in a quarter of patients; difficulty breathing, cardiac failure, symptoms of meningitis or encephalitis may be present
  • Leucopenia and thrombocytopenia are common.
  • Joint symptoms usually last for a few days or weeks; may last for several months or even for years in some patients.

Diagnosis

  • Antibody determination; the date of falling ill and the travel history are helpful additional information

Treatment

  • No specific treatment exists.
  • NSAID

Prognosis

  • Good; prolonged joint symptoms are possible

Prevention

  • Prevention of mosquito bites, also in the daytime (clothing, repellents)
  • No vaccine exists.

Japanese encephalitis

Causative agent

  • A flavivirus (arbovirus)

Epidemiology

  • Occurs in a wide area in Asia, from India to Japan and Papua New Guinea (see http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/japanese-encephalitis.aspx).
  • The disease is most prevalent in India and Southeast Asia.
  • As pigs and birds are the natural hosts of the virus the disease occurs particularly in the countryside and in growing slum areas.
  • In tropical areas the disease is found the year round while in subtropical areas north of the 17th parallel it is most commonly found from May to October.

Route of infection

  • The infection is transmitted by mosquitos. The disease is spread by Culex mosquitos that are active in the evening and at night.

Global significance

  • Important cause of viral meningoencephalitis in children in endemic areas
  • The vaccine is included in the national vaccination programme in many countries within endemic areas.

Symptoms

  • The incubation period is 4-14 days.
  • The symptoms vary from a febrile illness with headache to severe meningitis or encephalitis.

Diagnosis

  • Antibody determination

Treatment

  • No specific treatment exists.

Prognosis

  • Of the patients who fall ill with encephalitis one third die, one third get permanent neuropsychiatric sequelae and one third recover fully.

Prevention

  • Prevention of mosquito bites, also in the daytime (clothing, repellents)
  • The newer, inactivated vaccine (Ixiaro® ) is produced in Vero cell cultures. It is safe and well tolerated. The vaccine is given in 2 injections on days 0 and 28.For a person planning a new trip, a single booster is sufficient 12-24 months after the basic series.
  • The older vaccine, JEV-GCC, was produced in the brain cells of mice and has largely been replaced by the new vaccine due to its adverse effects profile. For persons who have been vaccinated with a full series of JEV-GCC, a single dose of Ixiaro® is sufficient as a booster.
  • Vaccination is not needed on short tourist trips, but it is recommended for anyone who plan to stay a longer time, e.g. for more than 4 weeks, in an endemic area, particularly in the countryside Vaccines for Preventing Japanese Encephalitis.

Yellow fever

Causative agent

  • A flavivirus (arbovirus)

Epidemiology

  • Yellow fever is found in Africa around the equator(90% of cases) and in South America in the Amazonas. The disease is not found in Asia (see http://www.who.int/csr/disease/yellowfev/impact1/en/index.html). In 2015-2016, there was a large epidemic in Angola, which raised concern over sporadic cases of yellow fever in guest workers returning from epidemic areas to their homes in Southeast Asia, since there are vector mosquitos in Asia and local spread of the disease is possible in theory. An extensive international vaccination campaign was launched in the epidemic area in Africa, which brought the epidemic under control; no new cases were seen in Asia.

Route of infection

  • The infection is transmitted by mosquitos. Vectors include Aedes aegypti and Haemagogus mosquitos that are active in the daytime.

Global significance

  • Large epidemics occur occasionally.

Symptoms

  • The incubation period is 3-6 days.
  • The clinical picture varies from a mild febrile disease to a severe form with headache, myalgia, hepatic and renal dysfunction and haemorrhages.

Diagnosis

  • Antibody determination; specific request for yellow fever

Treatment

  • No specific treatment exists.

Prognosis

  • The overall mortality of yellow fever is 5%, 20-50% for the icteric form.

Prevention

  • An effective vaccine against yellow fever is available. It is a live attenuated vaccine not to be given to pregnant women or to immunocompromised persons. At times, there has been global shortage of vaccines.
  • In infants less than 9 months of age the vaccine has been found to cause adverse effects of such magnitude that they usually should not be vaccinated. The risk of adverse effects is also increased in persons over 60 years of age, and the need for vaccination should be carefully deliberated in this age group. If a person is left non-vaccinated the medical grounds should be recorded in an international certificate given to the person.
  • Yellow fever vaccination is the only vaccination that may be officially required by a border authority. An official vaccination certificate is usually required of persons arriving from endemic areas. In some Western African countries the certificate is required of all travellers.
  • Booster vaccines used to be required every 10 years, but according to WHO, a person who has been vaccinated once does not need a booster vaccine. The vaccination certificate becomes valid 10 days from the injection.
  • Avoidance of mosquito bites (clothing, repellents)

Zika virus infection

Causative agent

  • Zika virus (ZIKV) is a flavivirus (arbovirus).

Epidemiology

  • Zika virus was originally found in Uganda in 1947. Minor zika virus epidemics and sporadic cases of disease have been reported from West and Central Africa and Southeast Asia for a long time.
  • In the 21st century, the virus has been found in new regions. It caused an epidemic in Micronesia in 2007, in French Polynesia in 2013-2014 and in Chile in 2014. In 2015, the first zika virus infections were confirmed in Brazil and the virus caused an extensive epidemic in South America and Middle America and on the Pacific Islands. The disease was also found in North America. During this epidemic, an association was found with a severe foetal developmental disturbance (microcephaly) and with the Guillain-Barré syndrome.

Route of infection

  • The infection is usually acquired through a mosquito bite. The vectors are Aedes aegypti and Aedes albopictus mosquitos that are active in the daytime. The latter is also found in the Mediterranean region.
  • The infection is transmitted from mother to foetus during pregnancy.
  • The infection may also occur through sexual contact. The virus remains in the semen longer than in the blood.

Global significance

  • The virus is believed to be spreading to ever wider areas because the vector mosquitos are found in wide areas globally.

Symptoms

  • Incubation period is 3-12 days.
  • Most cases are asymptomatic or with mild symptoms.
  • Fever, rash, arthralgia, conjunctivitis
  • Symptoms last for several days and up to one week.
  • The clinical picture is usually mild and does not require any hospitalization. Many patients do not even visit a doctor.

Diagnosis

  • Laboratory tests to diagnose Zika virus infection include a serum- or urine-based nucleic acid detection test or a combination test that includes dengue virus antibodies and antigen and zika virus antibodies, because serological cross-reactions between these viruses are very common.

Treatment

  • There is no specific treatment available.

Prognosis

  • The disease is mostly mild and resolves spontaneously.
  • An infection during pregnancy is associated with a risk of foetal developmental disturbance (microcephaly).
  • ZIKV infection is associated with Guillain-Barré syndrome but the complication is rare.

Prevention

  • Protection against mosquito bites
  • No vaccine is available yet.
  • Pregnant women are recommended to avoid travelling to areas where ZIKV is actively spreading.
  • A woman returning from the epidemic area or recovering from a ZIKV infection should postpone possible planned pregnancy by 8 weeks.
  • A man returning from the epidemic area should refrain from unprotected sexual contact
    • for 8 weeks if he has not had symptoms suggesting a ZIKV infection
    • for 6 months after the symptoms have subsided if he has had symptoms suggesting a ZIKV infection or if the infection is laboratory-confirmed.

West Nile virus (WNV) infection

Causative agent

  • The West Nile virus (WNV) is a flavivirus (arbovirus).

Epidemiology

  • WNV was first reported in humans in 1947 in the West Nile area in Uganda, and in 1953 it was found in birds in the Nile region. Human infections have been reported for over 50 years in various countries.
  • In 1999, WNV that had been circulating in Israel and Tunisia was transmitted to New York, causing an epidemic with 62 cases of encephalitis and 7 deaths recorded. From there, the disease spread as an extensive epidemic throughout the USA over the next few years, and today it is endemic on the American continent from Canada to Venezuela. The epidemic in the USA in 1999-2010 showed that the spread of vector-borne viruses to new regions is a globally significant health threat.

Route of infection

  • The infection is usually acquired through a mosquito bite after the mosquito has first bitten a WNV-infected bird. The vector is mosquitos of the Culex genus.
  • Passerines act as the reservoir for the virus in nature. In birds, WNV may cause prolonged high-level viraemia, during which the viruses multiply. The birds are usually asymptomatic.
  • In humans, viraemia is of a low level and the disease is not spread from person to person by mosquitos. Transmission from one person to another is possible in association with blood transfusion or organ transplantation or from mother to foetus or to a breastfed baby.

Global significance

  • WNV is one of the most wide-spread arboviruses.
    • It has spread quite widely in the Old World, throughout Africa and the Middle East, and in parts of Europe and the former Soviet Union, South Asia, Australia and the American continent.
  • In 2019, 443 cases were reported in Europe, and 422 of them were endemic. Most of the cases were diagnosed in Greece (65%) and Italy (13%). According to the ECDC, the case fatality rate was 12%. See also http://www.ecdc.europa.eu/en/west-nile-fever/facts/factsheet-about-west-nile-fever.

Symptoms

  • The incubation period is 2-14 days.
  • The disease is asymptomatic in most cases. Of those infected, 1 in 25 get symptoms and about 1 in 200 a neuroinvasive form of disease.
  • The most common symptoms are fever, headache and myalgia.
    • In some patients fever is absent or only mild.
    • Back pain, ophthalmodynia, pharyngitis, diarrhoea or vomiting may occur.
    • 25-50% of patients have a rash, which often occurs for about a week after fever.
  • Neuroinvasive disease usually appears as encephalitis, meningitis or flaccid paralysis or various combinations of these. Other neurological symptoms (such as the Guillain-Barré syndrome) are also possible.
  • Some patients have ophthalmological symptoms, such as chorioretinitis or retinal haemorrhages.
  • Other possible symptoms include rhabdomyolysis, multiorgan failure, hepatitis, pancreatitis and myocarditis.
  • After symptomatic disease, many patients have prolonged symptoms, such as fatigue, memory problems, weakness, headache and balance problems.
  • The most significant risk factor for neuroinvasive disease is advanced age; underlying diseases may also be predisposing factors.

Diagnosis

  • WNV antibodies in blood or CSF. Cross reactions with other flaviviruses are common.
  • The laboratory can be asked about the availability of PCR diagnosis.

Treatment

  • Since there is no specific treatment, the treatment is symptomatic.

Prognosis

  • The disease resolves spontaneously.
  • More than half of those with neuroinvasive disease have sequelae 12 months later.
  • The neuroinvasive disease is associated with 10% mortality.

Prevention

  • Protection against mosquito bites (clothing, repellents)
  • No vaccine is available yet.
  • In Finland, persons who have been in endemic areas must not donate blood during the first 28 days after returning to Finland. Country-specific variation may apply.

Disease-specific pages of ECDC and CDC

ECDC: European Centre for Disease Prevention and Control; CDC: Centres for Disease Prevention and Control (USA)

    References

    • Kularatne SA. Dengue fever. BMJ 2015;351:h4661. [PubMed]
    • Erra EO, Kantele A. The Vero cell-derived, inactivated, SA14-14-2 strain-based vaccine (Ixiaro) for prevention of Japanese encephalitis. Expert Rev Vaccines 2015;14(9):1167-79. [PubMed]
    • Wasserman S, Tambyah PA, Lim PL. Yellow fever cases in Asia: primed for an epidemic. Int J Infect Dis 2016;48:98-103. [PubMed]
    • Focosi D, Maggi F, Pistello M. Zika Virus: Implications for Public Health. Clin Infect Dis 2016;63(2):227-33. [PubMed]