Arboviruses

An arbovirus, short for arthropod-borne virus, is defined by how it is transmitted rather than by what it is. The label is ecological and epidemiological, not taxonomic: it groups viruses from several unrelated families that share one way of life, cycling between a vertebrate host and a blood-feeding arthropod that the virus must itself infect. The great majority of human arboviral disease is caused by agents from the families Flaviviridae and Togaviridae and the order Bunyavirales, with a smaller contribution from the Reoviridae.

A virus qualifies as an arbovirus only if it meets all four of the following conditions:

1. It infects a vertebrate host, such as a person, bird or other mammal.
2. It is transmitted by a blood-feeding, or haematophagous, arthropod: a mosquito, tick, sandfly or biting midge.
3. It undergoes biological transmission, replicating inside the vector’s own tissues rather than riding on its mouthparts. After an infectious blood meal the virus infects the arthropod’s gut, crosses its body cavity (the haemocoel) and reaches the salivary glands, an obligatory replication step called the extrinsic incubation period.
4. It reaches a viraemic threshold in the host, producing enough virus in the blood for the next feeding arthropod to acquire an infectious dose.

What the definition excludes is as instructive as what it includes. An arthropod that carries virus only on contaminated mouthparts, passing it between hosts without the virus replicating inside it, performs mechanical transmission, and the virus it moves is not an arbovirus. Even if a mosquito takes up human immunodeficiency virus (HIV) or hepatitis B virus (HBV) in a blood meal, the virus is digested in the gut rather than replicating and reaching the salivary glands, so neither is an arbovirus.

Shared ecology, not shared ancestry, unifies the group. The same reservoir and vector concepts that shape viral emergence recur across every arbovirus family, which is why a clinician can often reason about an unfamiliar arbovirus from its vector, its geography and the syndrome it produces before the specific agent is identified.

Classification: families, genomes and vectors

The arboviruses are best learned first by family, because family predicts genome structure, replication strategy and the broad clinical possibilities.

Group	Genome	Representative genera	Principal vectors	Key human arboviruses
Flaviviridae	Positive-sense RNA, ~11 kb, single polyprotein	Orthoflavivirus	Aedes and Culex mosquitoes; Ixodes ticks	Dengue Zika Yellow fever West Nile Japanese encephalitis Tick-borne encephalitis
Togaviridae	Positive-sense RNA, ~11 to 12 kb, two open reading frames	Alphavirus	Aedes, Culex, Culiseta mosquitoes	Chikungunya Sindbis Ross River O’nyong-nyong Eastern, Western and Venezuelan equine encephalitis
Bunyavirales	Segmented negative-sense or ambisense RNA, three segments	Orthobunyavirus, Phlebovirus, Orthonairovirus	Mosquitoes, sandflies, Hyalomma ticks	Rift Valley fever Crimean-Congo haemorrhagic fever La Crosse Oropouche
Reoviridae	Segmented double-stranded RNA, twelve segments	Coltivirus	Dermacentor ticks	Colorado tick fever
Rhabdoviridae	Negative-sense RNA, non-segmented	Vesiculovirus	Sandflies, mosquitoes, midges	Chandipura virus Vesicular stomatitis virus
Orthomyxoviridae	Segmented negative-sense RNA	Thogotovirus, Quaranjavirus	Ticks	Thogoto virus Dhori virus Bourbon virus

The Rhabdoviridae and Orthomyxoviridae are included for completeness: both contribute only rarely to human arboviral disease, the former mainly through Chandipura virus, a cause of sandfly-borne encephalitis in India, the latter through the tick-borne Thogoto, Dhori and recently emerged Bourbon viruses.

Flaviviridae

The genus Orthoflavivirus (renamed from Flavivirus under current International Committee on Taxonomy of Viruses, or ICTV, nomenclature) contains around 50 species of small, enveloped, positive-sense ribonucleic acid (RNA) viruses whose 11 kilobase genome is translated as a single polyprotein. The genus divides ecologically into mosquito-borne flaviviruses (dengue, Zika, West Nile, Japanese encephalitis and yellow fever viruses), tick-borne flaviviruses (the tick-borne encephalitis complex) and a group with no known vector.

The medically important flaviviruses compared by vector, host and syndrome:

Virus	Vector	Reservoir or amplifying host	Primary syndrome
Dengue	Aedes aegypti	Humans in the urban cycle	Febrile illness; severe dengue with plasma leakage
Yellow fever	Aedes aegypti (urban); Haemagogus and Sabethes (jungle)	Non-human primates	Viscerotropic haemorrhagic fever with jaundice
Zika	Aedes aegypti	Humans and non-human primates	Mild febrile illness; congenital Zika syndrome
West Nile	Culex species	Birds; humans dead-end	Mostly subclinical; neuroinvasive disease
Japanese encephalitis	Culex tritaeniorhynchus	Pigs and wading birds; humans dead-end	Encephalitis
Tick-borne encephalitis	Ixodes ticks	Small rodents	Biphasic meningoencephalitis

Flavivirus vaccines:

Virus	Vaccine	Type
Yellow fever	Licensed	Live-attenuated 17D, single dose, lifelong protection
Japanese encephalitis	Licensed	Inactivated Vero-cell and live-attenuated
Tick-borne encephalitis	Licensed	Inactivated whole-virus, multi-dose with boosters
Dengue	Licensed	Live-attenuated tetravalent (for example Qdenga)

West Nile and Zika viruses have no licensed human vaccine.

The mature virion’s shell of envelope (E) and membrane (M) protein is the principal target of neutralising antibody. Maturation depends on cleavage of the premembrane (prM) protein by the host enzyme furin in the trans-Golgi network, and because this cleavage is often incomplete, circulating virions are a mixture of mature, partially mature and immature particles. This heterogeneity matters for both serology and for antibody-dependent enhancement, described below.

Togaviridae

The genus Alphavirus contains around 30 species of enveloped, positive-sense RNA viruses with a two-part genome: nonstructural proteins are translated from the genomic RNA, structural proteins from a separate subgenomic RNA. The genus divides clinically along a broad Old World and New World axis. Old World alphaviruses cause rash and arthritis (chikungunya, Sindbis, Ross River and o’nyong-nyong viruses); New World alphaviruses cause encephalitis (Eastern, Western and Venezuelan equine encephalitis viruses). The split is a generalisation, not a rule: arthritogenic viruses occasionally invade the central nervous system, and encephalitic viruses produce a systemic febrile prodrome first.

The cell-surface receptor Mxra8 specifically improves entry of the arthritogenic Old World clade and has no role for the encephalitic New World viruses, a molecular correlate of the clinical divide.

Bunyavirales

This order of segmented, negative-sense or ambisense RNA viruses contributes several medically important arbovirus genera: Orthobunyavirus (La Crosse encephalitis virus, Oropouche virus), Phlebovirus (Rift Valley fever virus, sandfly fever viruses) and Orthonairovirus (Crimean-Congo haemorrhagic fever virus, the only tick-borne member here). All carry a three-segment genome, large, medium and small, encoding the polymerase, the glycoproteins and the nucleocapsid protein respectively. They prime their messenger RNA by stealing host caps (cap-snatching) and assemble at the Golgi rather than the plasma membrane, which distinguishes their egress from the flaviviruses and alphaviruses. Their segmented genome also permits reassortment, the exchange of whole segments between two co-infecting viruses.

The genus Orthohantavirus belongs to this order but is not arthropod-borne: it spreads through inhaled aerosols of infected rodent excreta, a vertebrate-to-vertebrate route that places it outside the arbovirus definition. The hantaviruses form their own group, with a New World and Old World clinical division of their own.

Reoviridae

A small, taxonomically separate group of arthropod-borne Reoviridae, principally Colorado tick fever virus (genus Coltivirus, a non-enveloped double-stranded RNA virus transmitted by the Rocky Mountain wood tick Dermacentor andersoni), causes a biphasic “saddleback” febrile illness in the western United States and Canada. Its pathogenesis is distinctive: the virus persists inside red blood cells for weeks to months, shielded from neutralising antibody, so recovered patients are advised not to donate blood for at least six months.

Major human arboviruses at a glance

The following agents account for the great majority of human arboviral disease worldwide.

Virus	Epidemiology and vector	Clinical picture and key complication	Prevention and management	Key note
Dengue	Pantropical, >100 countries; Aedes aegypti; ~390 million infections/yr	Acute febrile illness; severe dengue with plasma leakage and shock at defervescence	Vector control; Qdenga vaccine; supportive fluid management	Second-serotype infection drives severe disease through antibody-dependent enhancement
Zika	Pantropical; Aedes aegypti; also sexual and transplacental spread; Americas 2015 to 2017	Mild febrile illness with rash; congenital Zika syndrome; Guillain–Barré syndrome	Vector control, pregnancy and sexual precautions; no vaccine; supportive	The only arbovirus with major sexual and transplacental transmission
Yellow fever	Sub-Saharan Africa, tropical South America; Aedes (urban), sylvatic mosquitoes (jungle)	Febrile illness; viscerotropic disease with jaundice, haemorrhage and renal failure	Live 17D vaccine (single dose); vector control; supportive	Vaccine required under International Health Regulations for endemic-area travel
West Nile	Africa, Europe, the Americas; Culex spp., bird reservoir; humans dead-end	Mostly subclinical; neuroinvasive disease in ~1 in 150, with encephalitis and acute flaccid paralysis	Vector control; no human vaccine; supportive	Commonest arboviral neurological disease
Japanese encephalitis	Asia and the Western Pacific; Culex spp.; pig and wading-bird amplification	Mostly subclinical; encephalitis with high case-fatality and neurological sequelae	Inactivated and live-attenuated vaccines in routine Asian childhood immunisation; supportive	Leading cause of viral encephalitis in Asia
Tick-borne encephalitis	Eurasia; Ixodes ticks; also unpasteurised dairy	Biphasic illness; second-phase meningitis or encephalomyelitis; Far Eastern subtype highest case-fatality	Effective inactivated vaccine; tick avoidance; supportive	Alimentary route via unpasteurised milk is distinctive
Chikungunya	Africa, Asia, Indian Ocean, the Americas; Aedes aegypti and Ae. albopictus	Fever with severe polyarthralgia; chronic arthritis in ~40%	Vector control; virus-like-particle vaccine (Vimkunya); supportive and analgesic	E1-A226V adaptation to Ae. albopictus drove spread into temperate regions
Sindbis	Northern Europe, South Africa; Culex and Culiseta spp., bird reservoir; humans dead-end	Itchy maculopapular rash, fever and arthritis; usually self-limiting	Vector control; no vaccine; supportive	Commonest cause of arboviral rash-and-arthritis in Southern Africa
Rift Valley fever	Sub-Saharan Africa, Arabian Peninsula; floodwater Aedes; livestock contact	Febrile illness; minority with haemorrhagic fever, encephalitis or retinitis causing visual loss	Livestock vaccination, occupational protection; supportive	Outbreaks follow heavy rainfall; occupational zoonosis
Crimean-Congo haemorrhagic fever	Africa, the Balkans, Middle East, Central and South Asia; Hyalomma ticks; livestock contact	Haemorrhagic fever with high case-fatality and hepatic involvement	Tick avoidance, strict barrier nursing; ribavirin (benefit debated); supportive	High nosocomial risk; requires viral haemorrhagic fever isolation
Colorado tick fever	Western United States and Canada; Dermacentor andersoni tick	Biphasic “saddleback” fever with leukopenia; rarely severe	Tick avoidance; no vaccine; supportive	Persists inside red cells for weeks; defer blood donation for ~6 months

Transmission cycles and host roles

Arboviruses are maintained in nature through cycles that can be pictured as three expanding rings, and much of outbreak control depends on knowing which ring a virus is in.

The innermost is the enzootic (sylvatic) cycle: quiet, self-sustaining transmission between wild vertebrates, usually non-human primates, rodents or birds, and the mosquitoes or ticks that feed on them, with no human involvement.

An epizootic (intermediate) cycle develops when the virus amplifies in domestic animals or spills into new hosts, often carried out of the sylvatic cycle by a bridge vector that feeds on both wild reservoirs and people or livestock. Venezuelan equine encephalitis amplifying in horses, Rift Valley fever amplifying in sheep and cattle after heavy rain, and Japanese encephalitis amplifying in pigs are all epizootic patterns.

The outermost is the epidemic (urban) cycle, human-to-mosquito-to-human transmission needing no animal host at all. Aedes aegypti, a highly anthropophilic, container-breeding mosquito that thrives in cities, sustains this cycle for dengue, chikungunya, yellow fever and Zika, and it is the urban cycle, not the older sylvatic one, that produces the largest outbreaks.

Whether humans drive transmission or merely receive it depends on the viraemia they generate. In the urban cycle humans are amplifying hosts: dengue, chikungunya and yellow fever reach titres high enough to infect a feeding mosquito, so a person becomes part of the transmission chain. For West Nile, Japanese encephalitis and Sindbis, humans (and horses) are dead-end hosts, infected but not viraemic enough to pass the virus on, so the chain stops with them.

Some vectors maintain a virus without any vertebrate host at all. Transovarial transmission, the passage of virus directly from an infected female to her eggs, lets Aedes mosquitoes carry Rift Valley fever and La Crosse virus through drought and winter, and lets Hyalomma ticks and Aedes eggs seed the next season’s outbreak. Ticks additionally pass virus transstadially, from one life stage to the next, which combined with lifespans measured in years makes them long-term reservoirs in their own right.

Vector biology also leaves an evolutionary signature. Mosquito-borne flaviviruses such as dengue have diversified explosively over the past two centuries, tracking expanding human and vector populations, while tick-borne flaviviruses evolve far more slowly, in a stepwise pattern that mirrors their stable, small-mammal ecology. A single mosquito species can serve more than one family: Aedes aegypti is the principal urban vector for dengue and Zika (Flaviviridae), chikungunya (Togaviridae) and historically yellow fever, and Aedes albopictus, with a wider temperate range, carried chikungunya into Europe after the virus adapted to it. Climate, urbanisation and the global trade in used tyres, a favoured Aedes breeding site, are recurring drivers of arbovirus emergence.

Clinical syndromes

Arboviral disease resolves into a small number of overlapping clinical syndromes, and organising by syndrome rather than by taxonomy is what drives the differential diagnosis at the bedside. A single virus can occupy more than one row.

Syndrome	Key pathogens	Classic features
Acute systemic febrile illness	Dengue, Zika, West Nile fever, Rift Valley fever (common form)	Abrupt fever, headache, myalgia, often a rash; usually self-limiting
Arthritogenic (rash and polyarthritis)	Chikungunya, Sindbis, o’nyong-nyong, Ross River	Maculopapular rash and debilitating, often chronic, symmetrical polyarthralgia
Neuroinvasive disease	West Nile, Japanese encephalitis, tick-borne encephalitis, the equine encephalitis viruses	Aseptic meningitis, encephalitis, and acute flaccid paralysis from anterior horn cell involvement in West Nile
Viral haemorrhagic fever	Yellow fever, severe dengue, Crimean-Congo haemorrhagic fever, Rift Valley fever	Coagulopathy, petechiae, mucosal bleeding, hepatic necrosis and high mortality

Two features deserve emphasis. The arthritogenic viruses, above all chikungunya, can leave symmetrical polyarthralgia that persists for months to years after the virus is cleared, a major cause of long-term disability rather than acute death. The neuroinvasive viruses cause disease in only a small minority of those infected, but that minority carries the highest morbidity of the syndrome; West Nile in particular can produce a poliomyelitis-like acute flaccid paralysis through anterior horn cell injury.

Exposure history, urban Aedes exposure versus a tick bite versus livestock contact, together with travel history, narrows the differential far more efficiently than laboratory testing alone. Exposure history is the single most useful piece of clinical information in suspected arbovirus disease.

The tick-borne encephalitis complex

Within the tick-borne branch of Flaviviridae, the tick-borne encephalitis (TBE) virus complex is the most clinically important grouping outside the mosquito-borne viruses. Three subtypes circulate across Eurasia: the European subtype, transmitted by Ixodes ricinus and generally milder; the Siberian subtype, associated with a more protracted and sometimes chronic course; and the Far Eastern subtype, transmitted by Ixodes persulcatus and carrying the highest case-fatality of the three.

TBE is unusual among arboviruses for a second, well-documented route beyond the tick bite: drinking unpasteurised milk or dairy products from an infected goat, sheep or cow, which carries the virus during the animal’s own viraemia.

The illness is classically biphasic: an initial nonspecific febrile phase, then an afebrile interval of about a week, then a second phase in a minority of patients in which the virus invades the central nervous system to cause meningitis, meningoencephalitis or meningoencephalomyelitis. The proportion reaching the second phase rises from the European subtype through Siberian to Far Eastern. Closely related tick-borne flaviviruses outside the complex include Powassan virus (the only North American tick-borne flavivirus) and Kyasanur Forest disease virus (India, with a haemorrhagic rather than purely encephalitic presentation). Unusually for arboviruses, effective inactivated vaccines exist for TBE and are used in risk-based immunisation across several endemic European countries.

Diagnosis: viral kinetics, serology and cross-reactivity

Arboviral diagnosis turns on the timeline of infection, because the virus and the antibody response are detectable at different stages and testing at the wrong moment produces a false negative.

In the early phase, roughly the first five days after symptom onset while the patient is viraemic, the virus itself can be detected directly by reverse-transcriptase polymerase chain reaction (RT-PCR) or, for dengue, by the secreted nonstructural protein 1 (NS1) antigen test.

In the late phase, from around day five, viraemia falls rapidly as the humoral response mounts, and diagnosis shifts to serology: immunoglobulin M (IgM) first, then immunoglobulin G (IgG). An RT-PCR requested on day 10 of a dengue or West Nile infection is likely to be falsely negative, which is why the test must be matched to the day of illness.

Serology carries its own trap. Flaviviruses share highly conserved epitopes on the envelope protein, so antibody against one flavivirus cross-reacts with the others: a patient with prior West Nile exposure may test falsely positive for dengue or Zika IgM. The confirmatory gold standard is the plaque-reduction neutralisation test (PRNT), which measures the titre of antibody needed to reduce viral plaques by a set proportion, usually 50% or 90%, and so identifies the specific infecting virus. A negative early serology that stays negative on a convalescent sample taken about two weeks later effectively excludes the diagnosis.

Antibody-dependent enhancement

Antibody-dependent enhancement (ADE) is the mechanism behind the most severe dengue disease and the reason dengue vaccination is not straightforward. Dengue has four serotypes, and infection with one gives lasting immunity only to that serotype.

On infection with a second, different serotype, sub-neutralising antibody from the first infection binds the new virus but fails to neutralise it. Instead the antibody-coated virus is taken up more efficiently into cells bearing Fc-gamma receptors, chiefly macrophages, driving higher viraemia and a cytokine response that increases vascular permeability. This is the principal driver of dengue haemorrhagic fever and dengue shock syndrome (DHF and DSS). The same logic explains why the first dengue vaccine, Dengvaxia, primes dengue-naive recipients for more severe disease and is restricted to the already-seropositive.

Prevention, vaccines and infection control

Licensed vaccines exist for only a minority of arboviruses, and the landscape changes faster than most areas of virology, so any vaccine claim should be treated as provisional.

Yellow fever’s live-attenuated 17D vaccine, in use since the 1930s, remains one of the most effective viral vaccines ever produced and is required for travel to and from endemic countries under the International Health Regulations. Inactivated and live-attenuated Japanese encephalitis vaccines are used in routine childhood immunisation across much of endemic Asia. For dengue, the tetravalent live-attenuated Qdenga (TAK-003) is World Health Organization (WHO) recommended for children in high-transmission settings and can be given to dengue-naive recipients, whereas the earlier Dengvaxia is restricted to people with confirmed prior infection. For chikungunya, a virus-like-particle vaccine (Vimkunya) is now the favoured product after the licence for an earlier live-attenuated vaccine (Ixchiq) was suspended over serious safety signals. No licensed human vaccine exists for Zika, West Nile virus or Sindbis.

Where no vaccine exists, vector control is the primary preventive tool: source reduction (eliminating standing-water breeding sites, especially discarded containers and used tyres), larvicide and adulticide application, and personal protection with repellents, protective clothing and bed nets. The most significant recent advance is biological: releasing mosquitoes carrying the bacterium Wolbachia, which reduces their competence to transmit dengue, Zika and chikungunya, alongside sterile-insect and gene-drive programmes now in deployment.

Infection prevention and control (IPC) is usually a matter of avoiding bites, because most arboviruses do not spread person to person. The critical exceptions are the tick-borne and contact-transmitted viral haemorrhagic fevers, above all Crimean-Congo haemorrhagic fever, which spreads readily from patient to staff through blood and body fluids and has caused documented nosocomial outbreaks. Suspected cases require strict barrier nursing and viral haemorrhagic fever isolation precautions, with appropriate personal protective equipment, rather than the standard precautions adequate for a mosquito-borne febrile illness.

South African context

South Africa’s important arboviruses are Sindbis, West Nile, chikungunya, Rift Valley fever and Crimean-Congo haemorrhagic fever. Sindbis and West Nile are the commonest causes of arboviral rash-and-arthritis and of arboviral neurological disease respectively, both maintained in a Culex-mosquito and avian-reservoir cycle on the central plateau. Chikungunya falls within the endemic range, but most diagnosed South African cases are in travellers returning from other endemic countries.

Rift Valley fever is a major local zoonosis: outbreaks follow heavy rainfall and flooding that hatch the floodwater Aedes vectors, human infection comes largely from occupational contact with infected livestock (abattoir workers, farmers and veterinarians), and retinal vasculitis causing lasting visual loss is a characteristic late complication. Crimean-Congo haemorrhagic fever is acquired from Hyalomma tick bites or from handling infected livestock tissue, and carries a high nosocomial risk that makes it the arbovirus most demanding of strict isolation.

Dengue, Zika and yellow fever are not endemic and are seen only in returning travellers. Arboviral disease is diagnosed most often in late summer, particularly after rainfall, and is thought to be under-diagnosed and under-reported, since most infections are mild and confirmation needs a specialised reference test.

All arboviral disease is a notifiable medical condition, but the urgency differs by agent, reflecting the severity of the haemorrhagic-fever agents.

Notification category	Timeframe	Arboviral conditions
Category 1	Notify within 24 hours	Rift Valley fever; Crimean-Congo haemorrhagic fever
Category 3	Routine notification	All other arboviral infections, endemic or imported (Sindbis, West Nile, chikungunya, dengue, Zika, yellow fever)

The National Institute for Communicable Diseases (NICD) Arbovirus Reference Laboratory provides the specialised serology and molecular testing this group requires. Clinicians submit a structured case-investigation form covering exposure history, travel and clinical syndrome alongside the specimen. Because the viraemic window is short and antibody takes several days to appear, a convalescent sample is often needed to confirm or exclude a suspected case.

References and recommended reading

• Pierson TC, Lazear HM, Diamond MS. Flaviviruses. In: Fields Virology, 7th edition, Chapter 9. Philadelphia: Wolters Kluwer; 2023. The principal source for flavivirus classification, clinical syndromes, antibody-dependent enhancement and pathogenesis.
• Griffin DE, Weaver SC. Alphaviruses. In: Fields Virology, 7th edition, Chapter 6. Philadelphia: Wolters Kluwer; 2023. The source for alphavirus classification, the Old World and New World clinical split and Mxra8 receptor biology.
• Spiropoulou CF, Bente DA. Orthohantavirus, Orthonairovirus, Orthobunyavirus, and Phlebovirus. In: Fields Virology, 7th edition, Chapter 17. Philadelphia: Wolters Kluwer; 2023. The source for the Bunyavirales arbovirus genera, Rift Valley fever and Crimean-Congo haemorrhagic fever.
• Petersen LR, Barrett ADT. Arthropod-Borne Flaviviruses. In: Richman DD, Whitley RJ, Hayden FG (eds.), Clinical Virology, 4th edition, Chapter 53. Washington: ASM Press; 2016. The foundational account of the mosquito-borne and tick-borne flaviviruses and the tick-borne encephalitis complex.
• Yukl S, Wong JK. Colorado Tick Fever and Other Arthropod-Borne Reoviridae. In: Richman DD, Whitley RJ, Hayden FG (eds.), Clinical Virology, 4th edition, Chapter 35. Washington: ASM Press; 2016. The source for Colorado tick fever virus.
• National Institute for Communicable Diseases. Arboviral Disease. NICD; 2025. The source for South African arbovirus epidemiology, notifiable-condition status and the reference-laboratory diagnostic pathway.