Elsevier

The Lancet

Volume 371, Issue 9611, 9–15 February 2008, Pages 500-509
The Lancet

Seminar
Pathogenic flaviviruses

https://doi.org/10.1016/S0140-6736(08)60238-XGet rights and content

Summary

Haemorrhagic disease, encephalitis, biphasic fever, flaccid paralysis, and jaundice are typical manifestations of diseases in human beings after infections by mosquito-borne or tick-borne flaviviruses such as yellow fever, dengue, West Nile, St Louis encephalitis, Japanese encephalitis, tick-borne encephalitis, Kyasanur Forest disease, and Omsk haemorrhagic fever. Although the characteristics of these viruses are well defined, they are still unpredictable with increases in disease severity, unusual clinical manifestations, unexpected methods of transmission, long-term persistence, and the discovery of new species. This Seminar will compare the epidemiological and clinical features of the medically important flaviviruses, consider the effect of human activity on their evolution and dispersal, and draw attention to new findings and some of the unanswered questions, unresolved issues, and controversies that remain.

Introduction

The family Flaviviridae (genus Flavivirus) includes arthropod-borne viruses (arboviruses) that are transmitted to vertebrates by infected mosquitoes or ticks, producing disease in human beings and animals (table). Transmission by mosquitoes between people has only been reported for dengue virus, yellow fever virus, and West Nile virus that cause diseases in which human beings are usually dead-end hosts. Flavivirus evolution and epidemiology is largely determined by the ecological needs of their invertebrate and vertebrate hosts (figure 1). They can be grouped by nucleotide sequence, antigenicity, pathogenicity, geographic distribution, and ecological associations. For example, viruses related to Japanese encephalitis are usually associated with Culex spp mosquitoes that are ornithophilic (feed on birds) and tend to cause neurological infections. Viruses related to yellow fever virus are often associated with Aedes spp mosquitoes (Figure 1, Figure 2) that feed on humans, simians, and other mammalian species.3, 4, 5, 6 Dengue and yellow fever virus cause diseases in people that are characterised by vascular leakage and sometimes haemorrhage. Flaviviruses transmitted by Ixodes spp ticks cause neurological or haemorrhagic disease.3

Section snippets

Mosquito-borne flaviviruses

The type species, yellow fever virus, causes jaundice in people who are severely affected. Sporadic outbreaks arise in sub-Saharan Africa, and yearly incidence rates can reach 200 000 infections, including 30 000 deaths.4, 7 There are fewer reported cases in South America, Central America, and the Caribbean than in sub-Saharan Africa. African yellow fever virus circulates between Aedes spp mosquitoes and simians living in the African equatorial forests and surrounding savannah. Few African

What can be done to control the flaviviruses?

An effective and affordable vaccine for yellow fever virus, providing long-lasting immunity, has been widely available for over 50 years.4 However, elderly people may be vulnerable to extremely rare but serious adverse events resulting from use of the vaccine.63, 64 Another unresolved issue is whether it should be used only for outbreak control or incorporated into the Expanded Programme on Immunization in endemic countries. The virus circulates in the tropical jungles of Africa and South

Will flaviviruses cause epidemics in new geographic regions?

We have focused very briefly on pathogenic human flaviviruses. For most of these viruses, control is difficult because many hosts and vectors are involved. With increasing temperatures worldwide, movement of people, increasing human population densities, wider dispersal of competent mosquitoes or ticks, and transportation of goods, animals, and agricultural products, the continuing spread of these arboviruses into new regions seems probable. Furthermore, we might expect increasing numbers of

Search strategy and selection criteria

Cited references were accessed through recognised peer-reviewed journals or PubMed. Where possible, references were selected on the basis of originality (ie, first report on the subject) or their relevance to the subject discussed and their comprehensive nature and high quality. In some cases several references are cited because of their importance and to extend the depth of description.

References (78)

  • RN Charrel et al.

    Complete coding sequence of the Alkhurma virus, a tick-borne flavivirus causing severe hemorrhagic fever in humans in Saudi Arabia

    Biochem Biophys Res Commun

    (2001)
  • PF Vasconcelos et al.

    Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases

    Lancet

    (2001)
  • F Guirakhoo et al.

    Viremia and immunogenicity in nonhuman primates of a tetravalent yellow fever-dengue chimeric vaccine: genetic reconstructions, dose adjustment, and antibody responses against wild-type dengue virus isolates

    Virology

    (2002)
  • AG Pletnev et al.

    Chimeric Langat/Dengue viruses protect mice from heterologous challenge with the highly virulent strains of tick-borne encephalitis virus

    Virology

    (2000)
  • CH Calisher et al.

    Taxonomy of the virus family Flaviviridae

    Adv Virus Res

    (2003)
  • MW Gaunt et al.

    Phylogenetic relationships of flaviviruses correlate with their epidemiology, disease association and biogeography

    J Gen Virol

    (2001)
  • GK Strode

    Yellow Fever

    (1951)
  • RH Kokernot et al.

    Neutralizing antibodies against arthropod-borne viruses in the sera of domestic quadrupeds ranging in Tongland, Union of South Africa

    Ann Trop Med Parasitol

    (1961)
  • BM McIntosh et al.

    Culex (Eumelanomyia) rubinotus Theobald as vector of Banzi, Germiston and Witwatersrand viruses. II. Infections in sentinel hamsters and wild rodents

    J Med Entomol

    (1976)
  • CE Smith et al.

    Yellow fever in South Wales

    Med Hist

    (1986)
  • SB Halstead et al.

    Antibody-enhanced dengue virus infection in primate leukocytes

    Nature

    (1977)
  • S Halstead

    The Alexander D Langmuir lecture. The pathogenesis of dengue. Molecular epidemiology in infectious disease

    Am J Epidemiol

    (1981)

  • Dengue and dengue haemorrhagic fever. WHO factsheet

  • XT Cao et al.

    Evaluation of the World Health Organization standard tourniquet test and a modified tourniquet test in the diagnosis of dengue infection in Viet Nam

    Trop Med Int Health

    (2002)
  • S Green et al.

    Immunopathological mechanisms in dengue and dengue hemorrhagic fever

    Curr Opin Infect Dis

    (2006)

  • Dengue haemorrhagic fever. Diagnosis, treatment, control

    (1997)
  • NT Nhan et al.

    Acute management of dengue shock syndrome: a randomized double-blind comparison of 4 intravenous fluid regimens in the first hour

    Clin Infect Dis

    (2001)
  • B Wills et al.

    Comparison of three fluid solutions for resuscitation in dengue shock syndrome

    N Engl J Med

    (2005)
  • SB Halstead et al.

    Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered

    Yale J Biol Med

    (1970)
  • SB Halstead et al.

    Hemorrhagic fever in Thailand; recent knowledge regarding etiology

    Jpn J Med Sci Biol

    (1967)
  • MG Guzman et al.

    Dengue hemorrhagic fever in Cuba, 1981: a retrospective seroepidemiologic study

    Am J Trop Med Hyg

    (1990)
  • GP Kouri et al.

    Dengue haemorrhagic fever/dengue shock syndrome: lessons from the Cuban epidemic, 1981

    Bull World Health Organ

    (1989)
  • MG Guzman et al.

    Neutralizing antibodies after infection with dengue 1 virus

    Emerg Infect Dis

    (2007)
  • JR Anderson et al.

    Aedes aegypti vectorial capacity is determined by the infecting genotype of dengue virus

    Am J Trop Med Hyg

    (2006)
  • F Rodhain et al.

    Mosquito vectors and dengue virus-vector relationships

  • MM Khin et al.

    Transovarial transmission of dengue 2 virus by Aedes aegypti in nature

    Am J Trop Med Hyg

    (1983)
  • B Hull et al.

    Natural transovarial transmission of dengue 4 virus in Aedes aegypti in Trinidad

    Am J Trop Med Hyg

    (1984)
  • L Rosen et al.

    Transovarial transmission of dengue viruses by mosquitoes: Aedes albopictus and Aedes aegypti

    Am J Trop Med Hyg

    (1983)
  • L Rosen

    Sexual transmission of dengue viruses by Aedes albopictus

    Am J Trop Med Hyg

    (1987)

    • Cited by (608)

    • Potential of Ilhéus virus to emerge

      2024, Heliyon

    • Virome survey of the bat, Rhinolophus affinis, in Hainan Province, China

      2024, Microbes and Infection

    • Tick-borne encephalitis virus modulates sphingolipid and phospholipid metabolism in infected human neuronal cells

      2024, Microbes and Infection

    • Regulation of microglia-mediated inflammation by host lncRNA Gm20559 upon flaviviral infection

      2023, Cytokine

    • Linear epitope identification of monoclonal antibodies against the duck Tembusu virus NS1

      2023, Poultry Science

    • A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody

      2023, Cell Reports
    View all citing articles on Scopus
    View full text
    Copyright © 2008 Elsevier Ltd. All rights reserved.