Flaviviruses are a family of single-stranded RNA viruses that pose a global health challenge. Classified as arboviruses, they are transmitted to humans and animals through the bite of infected arthropods, primarily mosquitoes and ticks. These viruses circulate across tropical, subtropical, and increasingly temperate regions, causing severe neurological disease and hemorrhagic fever.
Defining the Flavivirus Family
Flaviviruses are enveloped viruses within the family Flaviviridae. The virus particle is spherical, measuring approximately 40 to 50 nanometers in diameter, and possesses an outer lipid envelope derived from the host cell membrane. The genetic material is a single molecule of positive-sense RNA, meaning it can be immediately translated by the host cell’s ribosomes upon entry.
The genome encodes a large polyprotein that is cleaved into three structural proteins—capsid (C), pre-membrane/membrane (prM/M), and envelope (E)—and seven non-structural proteins. The E protein mediates attachment to the host cell and fusion of the viral envelope with the cell membrane. Non-structural proteins are responsible for replicating the viral RNA and interfering with the host’s immune response.
Vectors and Spread
The transmission cycle of flaviviruses relies on arthropod vectors, with mosquitoes being the most common carriers. Aedes species, such as Aedes aegypti and Aedes albopictus, are the primary vectors for viruses like Dengue and Zika, while Culex mosquitoes spread West Nile Virus and Japanese Encephalitis. Ticks also serve as vectors for certain flaviviruses, including the agent that causes Tick-borne Encephalitis.
A mosquito becomes infected when it takes a blood meal from a viremic host, which can be an infected human, primate, or bird. The virus replicates within the mosquito before disseminating to the salivary glands. The mosquito then transmits the virus to a new host when it bites again, injecting viral particles along with its saliva. Humans are considered “dead-end” hosts for some flaviviruses like West Nile, but for others, like Dengue, humans are the main amplifying host in urban cycles.
Major Global Health Threats
Flaviviruses cause millions of infections annually and pose varied clinical threats. Dengue is the most prevalent, affecting up to 400 million people each year across tropical and subtropical regions. Most cases are mild, presenting with high fever, severe headache, and muscle and joint pain. A small percentage of cases can progress to severe dengue, characterized by plasma leakage, severe bleeding, and shock.
Zika virus typically causes a mild, self-limiting illness with a rash, fever, joint pain, and conjunctivitis. Its severity stems from its capacity for vertical transmission during pregnancy, resulting in Congenital Zika Syndrome (CZS). CZS is a constellation of birth defects, most notably severe microcephaly, brain calcifications, and ocular abnormalities.
Yellow Fever primarily affects Africa and South America, with symptoms progressing from fever and muscle pain to a toxic phase marked by jaundice, hemorrhagic manifestations, and “black vomit.” The fatality rate for those who enter the toxic phase can be as high as 20 to 50 percent. West Nile Virus is often asymptomatic in humans, but in approximately one percent of cases, it can cause severe neuroinvasive disease, including meningitis or encephalitis.
Prevention and Control Strategies
Preventing flavivirus infection relies on reducing human exposure to infected vectors and utilizing immunization strategies. Vector control is the most widely used public health intervention, focusing on the elimination of mosquito breeding sites through source reduction, such as removing containers that hold standing water. Chemical control methods involve the use of larvicides to treat water sources that cannot be eliminated and targeted application of adulticides, which are insecticides that kill adult mosquitoes.
Personal protective measures, including insect repellents containing DEET and permethrin-treated clothing, limit human-vector contact. Immunization offers protection, with a live-attenuated vaccine available for Yellow Fever that provides long-lasting immunity after a single dose. For Dengue, vaccines are now available, but their use is typically restricted to individuals in endemic areas, often with a history of prior Dengue infection, due to complex immune interactions.
Antiviral treatments for most flaviviruses, including Zika and Dengue, are not yet available, meaning patient care is primarily supportive. Research is ongoing into novel strategies, such as the deployment of mosquitoes infected with Wolbachia bacteria, which blocks the virus’s ability to replicate within the insect. The development of pan-flavivirus therapeutics and improved rapid diagnostics remains a priority for global health security.