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Vector-Borne Viral Infections

Overview

Numerous diseases are transmitted by insect vectors. Most are restricted to the tropics and are only seen in more temperate regions as imported diseases, because of the requirement for certain arthropod vectors like the Anopheles or Aedes mosquitoes.

Several vector-borne tropical diseases are protozoal infections, caused by protozoan parasites which replicate and multiply rapidly inside the host, invade the blood stream and lymphatic vessels or tissues, such as the agent of the African trypanosomiasis (sleeping sickness), Trypanosoma brucei, which is transmitted by the bite of a tsetse fly; the agent of the American trypanosomiasis (Chagas disease), Trypanosoma cruzi, which is transmitted by 'kissing bugs'; and the agents of leishmaniasis, which are transmitted through bites of phlebotomie sandflies. But by far the most important vector-borne protozoal infection is malaria, due to one of several Plasmodium parasites which are transmitted by the bite of any one of the 50 species of Anopheles mosquitoes. Malaria is one of the most important diseases in the world, killing children aged less than 5 years and exacting an enormous toll in lives, in medical costs and in days of labor lost in tropical regions of Africa, Asia, and Central and South Americas [1] [2]. There is hope, however, that a vaccine against malaria may be available within a few years [3].

A great many viruses also are transmitted by arthropod bites, mostly mosquitoes or ticks, and for that reason fall under the generic name of "arboviruses" (arthropod-borne viruses) (for a review see [4]. Most of these viruses belong to the Alphaviridae family, which includes the Eastern, Western and Venezuelan equine encephalitis viruses (EEEV, WEEV and VEEV, respectively), the O'nyong nyong virus and the Chikungunya virus (Chik); and to the Flaviviridae family, which includes the yellow fever virus (YFV), the four dengue fever viruses (DV), the Japanese encephalitis virus (JEV), the West Nile virus (WNV) and the tick-borne encephalitis virus (TBEV), not to mention the Murray Valley encephalitis, the Omsk haemorragic fever, the Kyasanur Forest disease and the Saint-Louis encephalitis (SLE) viruses. Several members of the Bunyamviridae family also are transmitted by mosquitoes, such as the Rift Valley fever virus (RVFV) and the California encephalitis virus, while others, such as the Crimean-Congo hemorrhagic fever (CCHF) virus, are transmitted by ticks. Several of these viruses are the agents of viral haemorrhagic fevers (Table1)1.

Not surprisingly, arboviruses can cause vast epidemics with impressive numbers of cases of illness or deaths. Dengue, the most prevalent mosquito-borne viral disease, is estimated to cause 100 million infections each year, 250 000-500 000 of which are the cause of severe illness [5]. Major epidemics of JE were reported from India and Nepal during the past few years [6]. The Rift Valley fever is endemic in Western and Eastern Africa where epidemic outbreaks in thousands of humans parallel epizootic outbreaks in sheep and cattle [7]. More than 265 000 people were infected during the recent Chik outbreak in Réunion, as well as 1 400 000 people in 2006 in India [8]. Japanese encephalitis accounts for up to 50 000 cases of encephalitis every year with case fatality rates of about 25%.

Table 1. Vector-borne viral haemorrhagic fevers (HF) [Ae: Aedes]

1Other viruses that cause haemorrhagic fevers, such as the Hantavirus (Haemorrhagic fever with renal syndrome), Arenaviruses (Lassa virus, Junin virus), or filoviruses (Ebola, Marburg) are not vector-borne.

Significant epidemics of yellow fever have been found to occur almost every year in western Africa, with an estimated record 44 000 cases and 25 000 deaths in Nigeria in 1987-88. A 2001 YF outbreak in Abidjan, Côte d'Ivoire, required immunizing 2.6 million persons in 12 days. WHO estimates that there may be up to 200 000 cases of YF a year in western Africa, with 30 000 deaths, prompted GAVI and WHO to launch a major initiative to vaccinate more than 48 million people in 12 West African countries over the next 5 years [9], using the live attenuated 17D YF vaccine, which is mandatory for travelers to endemic areas of Africa and South America.

The epidemiology of arbovirus infection in man is influenced by the probability of contacts between the vector, the human population and, for many viruses, the amplifying vertebrate host, whether birds (most arboviruses that cause encephalitis), monkeys (YFV, KFV), horses (EEEV, WEEV, VEEV, WNV), sheep (RVF), pigs (JEV) or rodents, which serve as reservoir for the virus. Several arboviral infections are actually expanding geographically, as exemplified by the emergence of WNV in the Americas or JEV in Australasia, the spread of dengue, the reemergence of YFV in South America [10] [11] and the recent outbreak of Chik in northern Italy. Both yellow fever and dengue are transmitted between humans by Aedes aegypti, which are anthropophilic mosquitoes that breed in urban dwellings. Why is dengue virus much more widespread than yellow fever virus, which has never appeared in Asia, is not known. It may have to do with the fact that dengue occurs mainly in urban areas whereas outbreaks of yellow fever arise in remote areas. Moreover, dengue virus can be transmitted transovarially and sexually through mosquito populations [12] .

Japanese encephalitis is widespread over South and South East Asia and Australasia, from Pakistan to the shores of Australia. The virus infects Culex spp mosquitoes that feed on birds, humans, pigs, horses, and breed in rice paddy fields. New irrigation projects that support agricultural development therefore increase the risk of disease outbreaks. As to West Nile virus, it attracted attention as a major pathogen after an unexpected outbreak of fever and encephalitis occurred in New York City in August 1999. Within a few weeks of its emergence on the American continent there were 62 confirmed cases and seven deaths among elderly people. The virus, which most likely had been introduced from Israel or Egypt [13] dispersed and spread throughout North America within the next five years.

In addition to protozoans and viruses, arthropods can also transmit bacteria, such as Borrelia spirochaetes responsible for Lyme disease and for louse-borne and tick-borne relapsing fevers, Yersinia pestis, the agent of plague, or Bartonellas and Rickettsias that are responsible for a variety of spotted fevers, including the Rocky Mountain spotted fever, typhus and Q fever.

This review will deal with Dengue, Japanese encephalitis (JE) and Malaria, which are the three most important mosquito-borne diseases in terms of morbidity and mortality and for which a vaccine is already available (JE) or will hopefully be available within the next five years; and with leishmaniasis, for which there unfortunately is no hope of a vaccine soon. Neither Tick-borne encephalitis (TBE), which is prevalent in an area that stretches from the West part of France up to Japan [14] nor Yellow fever, which is prevalent in most of West Africa and central South America will be discussed here, as efficient vaccines exist to fight them.