|
|
|
 |
| Emergency Medical Services and Trauma ● Health Alert Network ● Health Hotline ● Emergency Preparedness & Response |
  |
|
|
Flaviviruses Fact Sheet Flaviviruses are a particular group of viruses responsible for causing some of the worst human diseases, such as yellow fever, dengue hemorrhagic fever, Japanese encephalitis, and tick-borne encephalitis. These viruses, which have been known to plague mankind for centuries, afflict people of all ages and races and cause thousands of deaths every year. Although many countries have been successful in controlling these menaces, they continue to cause large epidemics in many areas of Asia, Africa, and Latin America. Despite the strides in medical technology and public sanitation, flaviviruses are still capable of causing regular outbreaks because effective vaccines against these agents have not been developed. Researchers have been trying to understand flaviviruses in greater detail in the hope of discovering something about their pathology that could lead to the creation of highly protective and long-lasting vaccines. Because flaviviruses are important human pathogens, it is important that people understand more about the nature of these viruses, the diseases they cause, the way they are transmitted, and how they can be controlled. The yellow fever virus, the first flavivirus shown to cause a human disease, is frequently used as a model to describe the flavivirus genus, whose members share similar molecular and pathological properties, for instance, protein and genetic composition, replication mechanism, and infection pathway. Because the yellow fever virus was the first flavivirus to be discovered and clinically described its genus was titled after its Latin name - "flavi-" being the Latin word for "yellow," hence "flavi-virus." The yellow fever virus was once greatly feared and is still capable of causing large epidemics. The virus originated in Africa and was brought to the Americas with European colonization and the introduction of slaves during the seventeenth and eighteenth centuries. For many decades following its introduction to the Americas, yellow fever was continuously epidemic among Native Americans and European settlers in the Caribbean zone. It did not take long for the virus to spread to the southern and eastern coasts of the U.S., where it struck major cities add ports such as Philadelphia, New York, and Boston. The virus also spread up the Mississippi River from New Orleans, causing large outbreaks in cities along the river. The disease afflicted most urban dwellers and caused death rates of 20% or more of a city's original population, resulting in panic that led people to flee from their towns. The virus was also transported oversea to Europe, where it caused thousands of deaths in Italy, France, Spain, and England in the eighteenth century. Today, yellow fever can still appear in epidemic form in the tropical and subtropical regions of Africa, Asia, Latin and Central America, Indonesia, and northern Australia. In Africa and Latin America, reported outbreaks can reach up to hundreds of thousands of cases in a year, as in Nigeria between 1986 and 1991. Annually, there are officially reported 5,000 to 6,000 cases in Africa and 300 to 500 cases in Latin America, but these figures are significantly underestimated In recent year, epidemics of yellow fever have also spread to countries where the disease has rarely appeared such as Peru Bolivia, and Cameroon. In 1990, an outbreak in Cameroon caused up to 20,000 cases with 1,000 deaths. The yellow fever virus is transmitted in two consecutive cycles involving monkey and human hosts and mosquitoes. In the first cycle, the virus is transmitted by the mosquito Aedes africanus and other Aedes mosquitoes (in Africa) or by Haemogogus mosquitoes (in the Americas); monkeys serve as its reservoir, and the primary humans infected are those who enter deep forests and jungles. In the second cycle, the domestic mosquito Aedes aegypti, which lives in close relationship with humans, may transmit the virus, with humans being the sole hosts in the cycle. An epidemic is established when an individual infected in the first cycle passes the virus to Aedes aegypti, which spreads the infectious agent to any urban dweller in the second cycle. Yellow fever is mainly characterized by hemorrhage (excessive bleeding), caused by the growth of the virus in the kidney and heart, and jaundice (yellowish discoloration of tissues and bodily fluids), caused by the growth of the virus in the liver. The disease begins abruptly with fever, chills, anorexia, nausea, vomiting and minor bleeding. After three days, the initial symptoms reach their worst state, and additional symptoms such as jaundice, dehydration, and severe hemorrhages begin to appear. Death, which occurs in about 20 - 50 % of all cases, usually happens during the seventh to tenth day of illness as a result of extensive liver damage. This final stage is generally preceded by deepened jaundice, uncontrolled hemorrhages, rising pulse, agitated delirium and coma - the terminal signs. Other flaviviruses have many properties in common with the yellow fever virus. Most of them are transmitted in cycles involving animals that serve as reservoirs (such as monkeys, bats, birds, and domestic animals), arthropods that serve as carriers (such as mosquitoes of the genera Aedes, Culex, or Haemogogus), and humans that serve as the final host. In addition, most of these viruses affect human populations in the tropical and subtropical areas of the world such as South and Southeast Asia, the Pacific Islands, Africa, the Caribbean and Latin America. The warm climate and heavy rainfall in these areas give rise to ideal breeding grounds for mosquitoes, which like to grow neat irrigated farms, flooded areas, jungles, rain forests, and swamps. However, not all flaviviruses follow these rules. The tick-borne encephalitis virus, for instance, is a flavivirus transmitted by ticks of the genus Ixodes, which thrive in temperate regions of Russia and Europe. The virus can only affect humans in areas where its carriers exist; hence, these diseases are usually native to a particular locality. Based on their carriers, flaviviruses can be divided into three major groups: the mosquito-borne group, (which includes the majority of flaviviruses), the tick-borne encephalitis group, and the group that lacks an arthropod carrier (this group is of least medical importance). A number of encephalitic diseases were
recognized in the nineteenth and twentieth centuries and were clinically
proven to be caused by flaviviruses. Among these were Japanese
encephalitis, St. Louis encephalitis, and tick-borne encephalitis. Like
yellow fever, these diseases frequently appear in epidemic form and
cause thousands of deaths each year. Japanese encephalitis is widely distributed in Asia, including Japan, China, India, Indonesia, and the Philippines. Every year, around 35,000 cases with 10,000 deaths are reported, but these figures are significantly underestimated Fewer than 20 cases now occur annually in Japan, but more than 10,000 cases occur in China and India. In tropical areas there is an endemic pattern of infection, with cases occurring sporadically throughout the year. In temperate zones, outbreaks have a marked seasonal incidence that corresponds to the density of the mosquito vector and the rate of virus transmission, which both depend on the temperature and the amount of rainfall. The main carriers of the Japanese encephalitis virus are the Culex mosquitoes, such as Culex vishnui (India), Culex gelidus and Culex fuscocephalus (Malaysia, Thailand), Culex annulus (Taiwan), and Culex annulirostris (Guam). The year-round transmission cycle of these viruses involve these mosquitoes as well as birds and pigs that serve as intermediate hosts. St. Louis encephalitis is a North American disease that frequently occurs in epidemic form in the U.S. The virus predominantly attracts the Ohio-Mississippi Valley, eastern Texas, Florida, and California, where its principal carriers, the Culen mosquitoes, are found In the Ohio-Mississippi basin and eastern Texas, the distribution of cases is urban-suburban, corresponding to high densities of Culen pipiens and Culex quinquefasciatus, which breed in polluted waters. In Florida, the tropical mosquito Culex nigripalpus is the epidemic vector, whereas in the western states, the principal carrier is Culen tarsalis. Since 1955, nearly 5,000 cases of St. Louis encephalitis have been officially reported in the U. S. The disease occurs in epidemic form at approximately ten-year intervals, with small numbers of notified cases (less than fifty per year). Tick-borne encephalitis occurs in an endemic pattern aver a wide area in Europe and eastern Russia corresponding to the distribution of lxodes, Dermacentor, and Haemaphysalis ticks. The intensity of transmission varies from year to year, with increases in small-mammal populations (the principal hosts for immature ticks) followed by rises in tick populations and a higher rate of human infection. The virus is maintained in nature in a cycle involving amplifying hosts such as shrews, moles, and hedgehogs, which have relatively stable populations, and large mammals, such as goats, sheep, and cattle, which serve as hosts for adult ticks. The disease is contracted by drinking raw milk from these infected domestic mammals, as the virus is excreted into the milk of animals during infection. Flaviviruses cause many other encephalitic diseases of less importance, among them Murray Valley encephalitis, West Nile fever, louping-ill, Rocio, and Powassan. These illnesses are also capable of causing epidemics and produce clinical features similar to those of the other encephalitic diseases. They are also transmitted by mosquitoes or ticks. The dengue virus has undergone a
dramatic expansion in range and has turned into a worldwide disease,
causing hundreds of millions of cases of dengue fever each year. The
cause of its worldwide spread can be attributed to expanding urban
populations and a coincident increase in the density of its carrier, as
well as the introduction of air travel and the rapid movement of
infected persons. Dengue fever occurs principally in the tropical areas
of Asia, Oceania, Africa, Australia, and the Americas, with the
mosquitoes Aedes aegypti, Aedes polynesiensis, and Aedes scutellaris
affecting Asia and the Pacific, and many other
Aedes mosquitoes
affecting West Africa. Like the yellow fever virus, the dengue virus is
transmitted in cycles involving monkey and human hosts and Aedes
mosquitoes. The clinical features are similar to those of yellow fever.
The initial symptoms include high fever, headaches, and muscular pain,
which are then followed by increased muscular and bone pain, anorexia,
nausea, vomiting, skin rashes, and weakness. Although the disease is
usually non-fatal, the virus can cause more severe illnesses
characterized by hemorrhage, as with dengue hemorrhagic fever, or shock,
as with dengue shock syndrome. Biological transmission of flaviviruses by arthropods (e.g., mosquitoes, ticks) depends upon the following: ingestion of a blood meal containing the virus; infection of skin cells; escape of the virus into the salivary glands; and finally, secretion of the virus in saliva when refeeding on an animal host. Most flaviviruses, which generally do not have any pathogenic effects on their carriers, are very specific in the kinds of hosts they infect. The differences in their infectiousness depend on the particular flavivirus involved and the host cell type. Infection is commonly lethal to animal cells, although same do not show these effects and become chronically infected Mosquitoes and ticks usually remain infected for life and produce extremely high levels of infectious virus particles in the salivary glands. Many vaccines developed in the past have limitations, including the need for repeated vaccination (the effect wears off after a period of time) and low protective efficacy (vaccinated individuals are vulnerable to the disease). Virologists have conducted research in the following areas in the hope of finding better vaccines: 1) the control of viral RNA synthesis during the course of infection, 2) the assembly of virus particles, and 3) the nature of the protein receptors used by flaviviruses to enter cells. These experiments have led to a new way to make effective vaccines Out of recombinant flaviviruses constructed from the genetic material of two different virus strains. Such a recombinant shows the characteristics of both parents since it contains portions of their genetic material. A recombinant can be made from any two flaviviruses, for instance, the yellow fever virus and the dengue virus. The RNA of the yellow fever virus is used as a backbone to hold genes, or specific genetic sequences that code for specific proteins, that are to be sliced out of the RNA of the dengue virus. With the help of techniques in molecular biology, selected genes of the dengue virus are removed and subsequently inserted into specifically chosen regions within the genetic backbone of the yellow fever virus, so that the resulting RNA strand - the genetic material of the new recombinant virus - contains genes from both viruses. However, not all recombinant viruses created in the laboratory will be living or functional like their parental strains, because the survival of a flavivirus depends on many factors, most importantly, whether or not the genes needed for survival are present in its RNA, and whether or not they are combined in the correct order. In fact, most efforts to construct living virus recombinants in the laboratory are unsuccessful, as it is difficult to arrive at the correct gene combination that can give birth to a living virus. Despite the obstacles encountered through the process, the successful creation of living recombinant viruses has potential implications for the development of an effective vaccine. These living recombinants can be made to be attenuated (weakened and non-lethal) so that they pose w harm to their hosts, yet still possess the antigenic properties of their parents. Live, attenuated viruses can be used in vaccines to help humans establish protective immunity against real infections by the parental viruses. Vaccines created from these viruses generally induce longer-lasting immunity than do some other vaccines. These viruses replicate and lead to the production of large amounts of antigen over a period of days or weeks that continue to stimulate the immune system. Furthermore, the viral antigens are presented in the context of normal viral infection and these vaccines induce the 111 range of immune responses from the animal host. The principal difficulty with live virus vaccines is the necessity to attenuate the virus sufficiently so that it does not cause disease, while retaining its potency for vaccination. Despite this difficulty, live attenuated virus vaccines have been extremely successful in the control of viral diseases.
|
|
Emergency Preparedness & Response Section |
Copyright � 2005 North Dakota Department of Health |