Mosquito-borne viral infections

• Several unrelated-looking illnesses in a returning traveller or a resident of the tropics—fever with severe headache, rash, joint pain, low platelets—are produced by viruses carried by mosquitoes, and dengue is the one that kills if fluids are given wrong.
• The same Aedes mosquitoes spread dengue, chikungunya and Zika, so travel history and the clinical picture matter more than a single test; chikungunya is the great arthralgia, Zika the quiet congenital threat, yellow fever the liver-and-bleeding illness, West Nile the encephalitis virus.
• There is no specific antiviral for any of them. Dengue is managed with careful fluid therapy and no aspirin or NSAIDs; yellow fever and Japanese encephalitis are supported; chikungunya is treated symptomatically.
• Yellow fever and Japanese encephalitis are vaccine-preventable; two-dose dengue vaccines exist in some countries, and several newer candidates are emerging.
• Prevention for all of them comes down to avoiding bites: repellent that is registered by the relevant authority, covered skin, screens and nets, and clearing standing water where mosquitoes breed.

By the end of this page you should be able to:

1. Name the mosquito vector, endemic region and hallmark clinical features of dengue, chikungunya, Zika, yellow fever and West Nile virus infection.
2. Recognise the WHO dengue warning signs and explain how they change management.
3. Interpret the basic dengue diagnostic algorithm by day of illness and choose fluids safely.
4. Differentiate chikungunya from dengue on clinical and laboratory grounds and explain why suspected chikungunya is managed as dengue until dengue is excluded.
5. Describe the pregnancy-related risks of Zika and yellow fever and know the vaccination restrictions for each.
6. Explain why a patient with meningitis or encephalitis in late summer needs West Nile (and Japanese encephalitis, if travel to Asia) considered.
7. Outline vector-control, repellent and vaccine measures for travellers and residents of endemic areas, including low-resource practice.

Mosquito-borne viral infections are a cluster of illnesses that medical students often meet as exam questions and later as fever in returning travellers. They are not a single disease. Each is caused by a different virus, carried by a different mosquito, in a different part of the world, and with a different target organ. What unites them is that the first 3 to 7 days of illness look similar—fever, headache, muscle and joint aches, rash—and that none has a specific curative drug.

This page treats five important ones together because they are what a clinician can hope to distinguish at the bedside: dengue, chikungunya, Zika, yellow fever and West Nile virus infection. Dengue dominates the page, because it is the most common severe infection of the group, it is the one that every clinician may have to manage, and a fluid error in dengue can kill a patient who would otherwise recover. Chikungunya is the crippling arthralgia, Zika the mild illness with serious fetal consequences, yellow fever the hepatitis and haemorrhage of Africa and South America, West Nile the encephalitis virus of temperate regions. Japanese encephalitis appears mainly in the prevention section because its vaccine is part of travel medicine.

The anchor for everything is the history: where the patient has been, in which season, and which mosquito bites them there.

Mosquito-borne viral infection means disease caused by a virus transmitted to humans through the bite of an infected mosquito. Most of the infections here are arboviruses—arthropod-borne viruses—spread by Aedes, Culex or Haemagogus mosquitoes. They are zoonoses in which humans are often dead-end hosts; nothing in this page requires the patient to have malaria, which is caused by a parasite spread by Anopheles and is covered separately.

Dengue is defined as fever with at least 2 clinical findings in a febrile person who lives in or has travelled to a dengue-endemic area within the last 14 days. The clinical findings are nausea or vomiting, rash, aches and pains, a positive tourniquet test, leukopenia, or any warning sign.^[1]

Dengue is then classified clinically as:

• Dengue without warning signs—no warning signs, hemodynamically stable, tolerating oral fluids.^[3]
• Dengue with warning signs—abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, or liver enlargement.^[1]
• Severe dengue—severe plasma leakage leading to shock or respiratory distress; severe bleeding; or severe organ impairment, including hepatitis with transaminases above 1,000 IU/L, impaired consciousness, or heart impairment.^[1]

This classification, from the WHO 2009 criteria as summarised by the CDC, exists to direct fluid therapy, not to diagnose. Many patients are managed on clinical grounds before any test returns.

Chikungunya is an acute febrile illness with polyarthralgia in someone with exposure to chikungunya transmission. The commonest presentation is an acute illness with fever, typically above 39 degrees C, and severe polyarthralgia, in a person with epidemiological exposure.^[5] The diagnosis is confirmed virologically.

Zika virus infection is usually a mild illness; approximately 80% of infections are asymptomatic.^[7] The important consequence is congenital infection.

Yellow fever ranges from a mild febrile illness to a severe form with jaundice, haemorrhage, shock and multisystem organ failure.^[9]

West Nile virus infection ranges from asymptomatic infection to West Nile fever to neuroinvasive disease (meningitis, encephalitis, acute flaccid myelitis).^[8]

Dengue is the most common mosquito-borne viral disease of humans. Its transmission is determined by the presence of Aedes mosquitoes, by warm wet seasons and by urban crowding with artificial water containers. It occurs in tropical and subtropical regions of Africa, the Americas, the eastern Mediterranean, South-East Asia and the western Pacific. Travel from non-endemic countries to endemic ones is the commonest way a medical student in a temperate country meets dengue, often with onset days after return.

Chikungunya shares the same Aedes vectors and therefore much of the same geography. It has caused large outbreaks in Africa, Asia, and the Indian Ocean, and, since 2013, in the Caribbean and the Americas. The name itself comes from a Makonde word for the stooped posture of the painful patient—an apt description of severe chikungunya arthralgia.

Zika was originally a zoonosis of African forests but now circulates in tropical and subtropical regions of Africa, Asia and the Americas, including large outbreaks with congenital consequences in Latin America.

Yellow fever remains endemic in Sub-Saharan Africa and tropical South America. Transmission occurs in three cycles: sylvatic (jungle), intermediate (savanna) and urban. In Africa, infants and children are at greatest risk in endemic areas because adults have acquired immunity; in South America, unimmunised young adults exposed through forest work are most often affected.^[9] For a two-week stay, the estimated risk to an unvaccinated traveller is about 50 cases per 100,000 in West Africa and 5 per 100,000 in South America; the corresponding risks of death are 10 and 1 per 100,000.^[9]

West Nile virus is the leading mosquito-borne illness of the contiguous United States, and transmission occurs wherever Culex mosquitoes meet infected birds and humans, especially in late summer and early autumn. Other regions with transmission include parts of Europe, Africa, Asia and the Middle East. Cases also follow blood transfusion and organ transplantation, so the diagnosis belongs in the differential for any unexplained encephalitis.

Japanese encephalitis is the most common vaccine-preventable cause of encephalitis in Asia and occurs across most of Asia and parts of the western Pacific.^[10]

All five infections here are RNA viruses spread by mosquito bites.

• Dengue virus is a flavivirus with four serotypes (DENV-1 to DENV-4). Infection with one serotype protects against that serotype for life, but a second infection with a different serotype is the main risk factor for severe plasma leakage, because antibody-dependent enhancement can increase viral uptake into cells.^[1][2]
• Chikungunya virus is an alphavirus.
• Zika virus is a flavivirus.
• Yellow fever virus is a flavivirus.^[9]
• West Nile virus is a flavivirus.^[8]
• Japanese encephalitis virus is a flavivirus closely related to dengue, West Nile and St. Louis encephalitis viruses.^[10]

The mosquitoes differ and this is what maps to geography:

• Aedes aegypti and Aedes albopictus (day-biting, urban, breed in containers) transmit dengue, chikungunya, Zika and urban yellow fever.^[9]
• Haemagogus and Sabethes mosquitoes transmit sylvatic yellow fever in the Americas.^[9]
• Culex mosquitoes (night-biting, often rural or suburban, associated with standing water and birds) transmit West Nile and Japanese encephalitis.^[8][10]

Humans are dead-end hosts for chikungunya, Zika, West Nile and yellow fever in most settings, so one sick person does not pass the virus directly to another. The exceptions that matter clinically are transplacental and perinatal Zika, and the rare perinatal transmission of yellow fever from a mother who is viraemic around delivery.^[9]

A mosquito inoculates virus into the skin. After local replication and regional lymph node spread, viraemia begins and lasts a few days. During viraemia the patient is infected, febrile, and—crucially for outbreak control—infectious to the next mosquito that bites them. This is the phase in which clinical presentation is generic and tests can separate the viruses.

Dengue then diverges. In typical dengue the patient has several days of fever with headache, retro-orbital pain, myalgia, arthralgia and rash. The dangerous moment is the end of the febrile phase, when capillary permeability abruptly increases and plasma leaks into the pleural and peritoneal spaces and into tissue. The critical phase is usually 3 to 8 days after fever onset.^[3] If intravascular volume is not supported, the patient develops shock; if too much fluid is given, the leaked plasma returns during recovery and the patient drowns in their own reabsorbed fluid. This narrow therapeutic window is why dengue fluid management is specific and why aspirin and NSAIDs, which increase bleeding risk in a thrombocytopenic patient with leaky capillaries, are avoided.

Chikungunya virus infects synovial tissue, which explains the severe and sometimes chronic arthralgia. Zika has a tropism for neural progenitor cells, which explains microcephaly and intracranial calcifications when infection occurs during pregnancy.

Yellow fever is a viscerotropic disease: hepatocyte infection produces the jaundice, and endothelial injury produces the haemorrhage. The hepatocyte infection is what makes the patient a bleeding risk, which is why aspirin and NSAIDs are avoided here too.

West Nile is neurotropic, infecting neurons and anterior horn cells, which explains meningitis, encephalitis, movement disorders and flaccid paralysis.

The history is the diagnosis until proven otherwise.

• Onset and course: abrupt fever; no focal source; symptoms 2 to 14 days after arrival in an endemic area (arboviral incubation periods range from 2 to 14 days).^[7][8]
• Destination and season: West Africa in the late rainy or early dry season suggests yellow fever; South-East Asia or the Caribbean in the wet season suggests dengue; rural Asia in transmission season suggests Japanese encephalitis; the United States or southern Europe in late summer suggests West Nile.
• Activities: forest work or jungle tourism for yellow fever; urban residence for dengue and Zika; camping near standing water for West Nile.
• Vaccination history: yellow fever, Japanese encephalitis and dengue vaccination status should be reviewed in every febrile traveller.^[2]
• Pregnancy: essential in every woman of child-bearing age with Zika suspicion or exposure.
• Medicines and red flags: aspirin, NSAIDs, and anticoagulants matter in dengue and yellow fever.

Presentations range from an undifferentiated febrile illness to severe dengue. The presumptive definition requires a febrile person from an endemic area with at least 2 of nausea or vomiting, rash, aches and pains, a positive tourniquet test, leukopenia, or a warning sign.^[1] Common symptoms include severe headache, retro-orbital pain, myalgia, arthralgia, fever and macular or maculopapular rash.^[2] Retro-orbital pain on eye movement is the classic, memorable feature; a flushed "dengue face" with maculopapular rash and mild haemorrhagic signs is typical. ^[3]

Warning signs are abdominal pain or tenderness, persistent vomiting (at least 3 episodes in 1 hour or at least 4 in 6 hours), clinical fluid accumulation (pleural effusion, ascites, pericardial effusion), mucosal bleeding (gums, nose, vagina or kidney), altered mental status with a Glasgow Coma Scale score below 15, liver enlargement of at least 2 cm below the costal margin, and a progressive rise in hematocrit on at least 2 measurements 6 hours apart.^[3]

Severe dengue is defined by shock or respiratory distress from severe plasma leakage, clinically significant bleeding, or severe organ involvement including hepatitis with transaminases above 1,000 IU/L, impaired consciousness or cardiac impairment.^[1]

On examination the clinician looks for signs of dehydration, capillary leak and shock: cold or clammy skin, narrow pulse pressure, tachycardia, prolonged capillary refill, postural hypotension and decreased urine output. A rising haematocrit with falling platelets is the laboratory signature of plasma leakage.

Chikungunya presents with acute fever, typically above 39 degrees C, and polyarthralgia that is usually bilateral and symmetric and can be severe and disabling.^[5] The incubation period is typically 3 to 7 days, with a range of 1 to 12 days.^[5] Other symptoms include headache, myalgia, arthritis, conjunctivitis, nausea, vomiting or a maculopapular rash.^[5] The majority of those infected become symptomatic.^{[5] [10]}

The arthralgia is the discriminator: it is far more prominent and disabling than in dengue, often affecting hands, wrists, ankles and feet, with periarticular swelling and effusion. Rare complications include uveitis, retinitis, myocarditis, hepatitis, nephritis, bullous skin lesions, haemorrhage, meningoencephalitis, myelitis, Guillain-Barre syndrome and cranial nerve palsies.^[5] Persons at risk of severe disease include neonates exposed intrapartum or shortly after birth, adults older than 65 years, and those with hypertension, diabetes or cardiovascular disease.^[5]

Laboratory findings can include lymphopenia, thrombocytopenia, elevated creatinine and raised hepatic transaminases.^[5] Comparatively, chikungunya more often produces high fever, severe arthralgia, arthritis, rash and lymphopenia, whereas dengue more often produces neutropenia, thrombocytopenia, haemorrhage, shock and death.^[5]

Acute symptoms typically resolve within 7 to 10 days, but a substantial proportion of patients have persistent or relapsing rheumatological symptoms—polyarthralgia, polyarthritis, tenosynovitis—for months to years.^[5] Mortality is rare and occurs mostly in older adults.^[5]

Approximately 80% of Zika infections are asymptomatic.^[7] The incubation period is 3 to 14 days. When symptomatic, the illness is typically mild and characterised by fever with maculopapular rash, arthralgia or non-purulent conjunctivitis, with myalgia and headache often as well.^[7] Symptoms last several days to a week.^[7]

Severe disease needing hospitalisation is uncommon and case fatality occurs in fewer than 1% of cases.^[7] Complications are rare but can include Guillain-Barre syndrome, encephalopathy, meningoencephalitis, myelitis, uveitis and severe thrombocytopenia.^[7]

The decisive issue is pregnancy. Infection during pregnancy can cause congenital Zika virus infection with serious birth defects of the brain and eyes: severe microcephaly, intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities and optic nerve abnormalities. Transmission during pregnancy can occur regardless of whether the mother was symptomatic. Infants may appear well at birth and only show neuroimaging findings or clinical sequelae, such as vision loss, later.^[7] Perinatal transmission is possible, so Zika should also be considered in an infant in the first 2 weeks of life with fever, rash, conjunctivitis or arthralgia (which in infants may show as irritability or refusal to use a limb) whose mother was potentially exposed within 2 weeks of delivery.^[7]

Most people infected with yellow fever virus have minimal or no symptoms and do not seek care. For those who become ill, the incubation period is typically 3 to 6 days. The initial illness is non-specific: backache, chills, fever, headache, myalgia, nausea and vomiting, and prostration.^[9] Most patients improve. After a brief remission of 48 hours or less, approximately 12% progress to a more serious form characterised by haemorrhagic symptoms, jaundice and eventually shock and multisystem organ failure. The case-fatality rate in severe cases is 30 to 60%.^[9]

Yellow fever therefore announces itself twice: a brief febrile illness, a short recovery, and then a dramatic second phase with bleeding gums and nose, haematemesis, melena, oliguria, and jaundice. This pattern, in an unvaccinated patient from an endemic area, is essentially diagnostic at the bedside.

An estimated 80% of human West Nile virus infections are subclinical or asymptomatic.^[8] The incubation period is typically 2 to 6 days, with a range of 2 to 14 days, and may be longer in immunocompromised patients.^[8]

Symptomatic non-neuroinvasive disease (West Nile fever) presents with fever, fatigue, headache, myalgia, arthralgia, transient maculopapular rash and gastrointestinal symptoms such as vomiting or diarrhoea.^[8] It is clinically indistinguishable from other viral febrile illnesses without testing.

Neuroinvasive disease occurs in fewer than 1% of infected patients and typically manifests as meningitis, encephalitis, or acute flaccid myelitis.^[8] Risk is higher in older individuals and the immunocompromised.^[8]

• Meningitis is clinically indistinguishable from other viral meningitides: fever, headache, photophobia and meningismus.^[8]
• Encephalitis is more severe, with fever, altered mental status and movement disorders such as tremor, myoclonus, parkinsonism and cerebellar ataxia.^[8]
• Acute flaccid myelitis can develop within 24 to 48 hours of illness onset, with limb weakness, paralysis, areflexia, cranial neuropathies and neuromuscular respiratory failure, and is clinically identical to poliomyelitis.^[8] WNV-associated Guillain-Barre syndrome can appear 1 to 8 weeks after acute infection, with ascending symmetric weakness and sensory and autonomic dysfunction.^[8]
• Rare complications include cardiac dysrhythmias, myocarditis, rhabdomyolysis, optic neuritis, uveitis, chorioretinitis, orchitis, pancreatitis and hepatitis.^[8]

Risk factors for neuroinvasive disease include age 65 years or older (about 2% develop neuroinvasive disease, against under 0.5% under 65), and any immunocompromising condition such as cancer, diabetes, hypertension, renal disease or immunosuppression.^[8] In patients aged 60 to 69 the risk of hospitalisation is twice that of younger adults, and in those aged 70 or older more than 6 times, with mortality of about 20% against about 2% under 50. Overall case fatality in neuroinvasive disease is approximately 10%, and higher still in older or immunocompromised patients; mortality is 30 to 40% in hematological malignancy, transplant recipients and patients on anti-CD20 therapy.^[8]

Most patients with non-neuroinvasive disease or meningitis recover completely, but fatigue and weakness can linger for weeks or months. Survivors of encephalitis or myelitis often have long-term neurological, cognitive and functional deficits; 30 to 40% are discharged to long-term care or rehabilitation, and more than half have symptoms beyond a year.^[8] Most infections confer lifelong immunity.^[8]

The presenting syndrome—fever plus aches plus rash in a traveller or a resident of the tropics—is broad. At the bedside the question is usually not which arbovirus, but whether the patient has a treatable bacterial infection, malaria, or dengue progressing to shock.

"4 out of 5" here means approximately 80%.

In acute mosquito-borne infection baseline tests usually include a full blood count, urea and electrolytes, liver function tests, glucose and a urinalysis. Dengue produces leukopenia and thrombocytopenia, with a rising haematocrit as plasma leaks. Chikungunya may produce lymphopenia and raised transaminases. West Nile meningoencephalitis produces a CSF lymphocytic pleocytosis with raised protein and normal glucose.^[8]

• In the acute phase, days 0 to 7, laboratory diagnosis should be made on serum, using either a nucleic acid amplification test and an IgM antibody test, or an NS1 antigen test and an IgM antibody test.^[2]
• Dengue virus RNA is usually detectable in the first 0 to 7 days.^[2]
• NS1 is detectable early and can be as sensitive as molecular tests during days 0 to 7.^[2]
• IgM can identify most recent infections after day 3 of illness, and convalescent testing is used when the acute sample is negative or unavailable.^[2]
• IgM persists for approximately 3 months, becoming less reliable over time.^[2]
• A positive NAAT or NS1 result is confirmatory, but a negative result does not rule infection out.^[2]
• A single positive IgM is "presumptive" recent infection, because of cross-reactivity with other flaviviruses such as Zika, West Nile, Japanese encephalitis, St. Louis encephalitis and yellow fever; plaque reduction neutralisation testing can resolve some false positives.^[2]
• IgG in a single specimen is not recommended for diagnosing acute dengue.^[2]

A clinician should take a serum sample early, but should never delay management while waiting for any of these results.^[2] Suspected dengue is treated according to its clinical group, regardless of whether the test is positive.

• Chikungunya: RT-PCR detects viral RNA in serum during the first 8 days of illness, viral culture in the first 3 days, and antibodies normally develop toward the end of the first week. To exclude the diagnosis, convalescent samples are needed for patients whose acute sample is negative.^[6] Positive chikungunya virus-specific IgM results should be confirmed by neutralising antibody testing.^[6]
• Zika: diagnosis rests on clinical features, travel dates and activities; laboratory diagnosis is usually performed on whole blood, serum or plasma, with urine recommended in pregnancy. Cross-reactivity with other flaviviruses complicates serology.^[7]
• Yellow fever: preliminary diagnosis is clinical and epidemiological; early diagnosis by virus isolation or nucleic acid amplification tests, because by the time jaundice is recognised the virus or RNA may no longer be detectable; serology for IgM and IgG, confirmed by plaque reduction neutralisation.^[9]
• West Nile: virus activity, season and clinical pattern point to the diagnosis, which is confirmed through CSF or serum IgM and neutralising antibodies submitted via the state or local health department.^[8]
• Japanese encephalitis: diagnosis is suspected in neurologic infection soon after residence in Asia. JE-specific IgM becomes detectable in CSF at 4 days or more after symptom onset and in serum at 7 days or more.^[10]

Dengue uses the WHO classification described above and manages each group differently. West Nile risk of neuroinvasive disease rises sharply with age and with immunocompromise, and that risk, rather than a numeric score, determines how closely the patient is monitored.^[8] There is no simple scoring system for chikungunya, Zika or yellow fever in routine use.

No specific antiviral drug exists for dengue, chikungunya, Zika, yellow fever or West Nile virus. Management is supportive for all, and for chikungunya, yellow fever and Japanese encephalitis this is explicitly the case.^[5][9][10] The major dangers are dengue shock and haemorrhage, yellow fever shock and bleeding, and neuroinvasive complications of West Nile and Japanese encephalitis, so the clinician's job is to recognise these early and support the patient through them.

All suspected dengue patients require appropriate management without waiting for diagnostic results, with monitoring for shock and for plasma leakage, which increases vascular permeability and risks organ damage.^[2]

Management is guided by the clinical group.^[3]

Dengue without warning signs (Group A): outpatient.

• Bed rest, abundant oral fluids, daily or clinically indicated CBC, fever control with acetaminophen or paracetamol, and teaching the patient to return immediately if warning signs appear.^[3]
• Avoid aspirin (acetylsalicylic acid) and NSAIDs such as ibuprofen.^[3]
• Oral hydration is usually sufficient; intravenous fluids are not assumed. Ambulatory patients can spread the infection to mosquitoes, so the patient should sleep under a mosquito net and household members should use an EPA-registered repellent for 3 weeks.^[3]
• Avoid routine corticosteroids and prophylactic platelet transfusions.^[3]

Dengue with co-existing conditions (Group B1): inpatient.

• Admit patients without warning signs but with conditions that raise severe-dengue risk (pregnancy, acute renal failure, coagulopathy, respiratory compromise) or who cannot tolerate oral intake; also consider admission case-by-case for comorbidities such as hypertension, diabetes, asthma, chronic kidney or liver disease, peptic ulcer disease, obesity with body mass index 30 kg/m2 or greater, or anticoagulant use, and for age under 1 year or over 65 years, or poor social access to care.^{[3] [5]}
• Encourage and monitor oral fluids, use acetaminophen, monitor for warning signs and compensated shock, and give intravenous fluids only if oral intake is inadequate or the clinical picture worsens.^[3]

Dengue with warning signs (Group B2): inpatient.

• Obtain a baseline CBC and monitor vital signs, intake, urine output and haematocrit every 4 to 6 hours, or more often as needed, especially during the critical phase around defervescence.^[3]
• Give an initial intravenous fluid bolus with isotonic crystalloids, such as normal saline or Ringer's lactate.^[3]
• Adjust intravenous fluids to the clinical condition and haematocrit trend, and reduce them gradually as the patient improves. Capillary permeability often normalises around 48 hours after defervescence, though this varies, so careful monitoring is required to avoid both under-hydration and fluid overload.^[3]

Severe dengue (Group C): intensive care.

• Severe plasma leakage with shock or respiratory distress, severe bleeding, or severe organ involvement.^[1]
• Monitor continuously or at least every 1 to 2 hours during the critical phase, tracking pulse pressure, capillary refill, mental status and repeated haematocrit.^[3]
• Give a first dose of intravenous crystalloid and up to 2 further doses; consider colloids such as albumin if there is no response to 2 to 3 crystalloid boluses.^[3]
• Blood transfusion is indicated for clinically significant active bleeding, particularly with haemodynamic instability, or when the haematocrit falls despite adequate fluid replacement, suggesting occult bleeding. Prophylactic platelet transfusions are not recommended.^[3]
• Corticosteroids are not routinely recommended unless a co-existing immune-mediated condition such as haemophagocytic lymphohistiocytosis or immune thrombocytopenia is present.^[3]

The single most important concept for a medical student is that the dengue patient who has just become afebrile is the one most at risk. Fever resolving marks the start of the critical phase in typical disease; the time to worry is not the febrile phase, when the patient looks unwell but compensates, but the day the temperature normalises and the blood pressure falls.

• Chikungunya: no specific antiviral. Treatment is symptomatic—rest, fluids, analgesics—and hospital admission for severe disease.^[5] Paracetamol or acetaminophen is recommended for pain relief and fever until dengue is excluded, because NSAIDs can increase bleeding risk; if analgesia is inadequate, narcotics or NSAIDs may be used after dengue has been ruled out.^[5] Because dengue and chikungunya co-circulate and are hard to tell apart, suspected chikungunya should be managed as dengue until dengue is excluded.^[5]
• Zika: care is supportive and centres on symptom control. In pregnancy, management involves consultation, ultrasound follow-up and appropriate referral; there is no specific antiviral treatment in standard adult care.
• Yellow fever: no specific medication is available, and a systematic review of antivirals (ribavirin, sofosbuvir, interferon), exchange procedures and liver transplantation found none improved outcome, so treatment is supportive—fluids, rest, analgesics and antipyretics—with avoidance of aspirin and NSAIDs in the first days, plus protection from further mosquito exposure to prevent feeding and onward transmission.^[9]
• West Nile: suspected neuroinvasive disease requires supportive care, airway protection, seizure control and monitoring for respiratory failure, particularly in acute flaccid myelitis.
• Japanese encephalitis: no specific antiviral treatment; therapy is supportive care and management of complications.^[10]

Vaccination records should be checked in every febrile patient who lives in or has travelled to an endemic area: dengue, yellow fever and Japanese encephalitis vaccines are directly relevant to diagnosis and to prevention.^[2] Cross-reactivity between flavivirus antibodies means a positive IgM rarely names the virus on its own.

• Dengue: shock from plasma leakage, severe bleeding, multi-organ impairment, fluid overload in recovery, and secondary infection in severe disease.
• Chikungunya: chronic disabling arthralgia and arthritis, neonatal infection with severe disease, cardiac and neurologic complications (rare).
• Zika: congenital microcephaly and other brain and eye defects; Guillain-Barre syndrome; perinatal transmission.
• Yellow fever: haemorrhage, shock, acute liver and renal failure; perinatal transmission from a viraemic mother.
• West Nile: chronic fatigue; long-term neurological, cognitive and functional deficits after encephalitis or myelitis; WNV-associated Guillain-Barre syndrome; congenital infection reported but uncommon.
• All: hospital-acquired infection and mosquito feeding on a viraemic patient sustaining urban transmission.

Dengue is usually self-limiting. With correct fluid management mortality in severe dengue should be low; with errors—either too little or too much—mortality rises. Chikungunya has a low mortality but a high burden of chronic disability, with a substantial proportion of care-seeking patients having joint symptoms for months to years. Zika in the adult is mild and brief; the fetal prognosis drives counselling. Yellow fever severe cases carry a 30 to 60% case-fatality rate. West Nile neuroinvasive disease carries approximately 10% fatality overall, rising markedly with age and immunocompromise, with long-term disability in many survivors. Japanese encephalitis carries 20 to 30% case-fatality, with serious long-term sequelae in 30 to 50% of survivors. ^[8][10]

Prevention is therefore not an afterthought for a medical student: it is the most powerful tool in the page.

For all mosquito-borne viruses, the foundation is avoiding bites:

• Use an EPA-registered insect repellent (follow label, particularly in children and pregnancy), wear long sleeves and trousers, and sleep in screened or air-conditioned accommodation or under a bed net. Bed nets are particularly important for chikungunya and Zika control in exposed households: when a patient has suspected or confirmed dengue, neighbours and family can be protected by net use and 3-week repellent use.^[3]
• The best protection for vector-borne disease generally is to avoid mosquito bites.^[9][10]
• Clear mosquito breeding sites: standing water in containers, gutters, tyres and flower pots. Aedes breed in clean water close to houses; Culex breed in polluted standing water and share urban and rural sites.
• Community and intersectoral programmes, rather than individual behaviour alone, determine urban Aedes control. Individual effort supports them.

No drug prophylaxis exists for any of these infections.

Yellow fever. A single dose of live-attenuated yellow fever vaccine (17D; YF-VAX in the United States) is recommended for people aged 9 months or older living in or travelling to risk areas of Africa or South America. Administer 0.5 mL subcutaneously as one dose; it is highly effective and antibody usually appears within days. The International Certificate of Vaccination or Prophylaxis becomes valid 10 days after primary vaccination and is considered valid for life, because WHO concluded that a single primary dose gives sustained, lifelong protection.^[9] A 0.1 mL fractional dose has been studied but is not approved by the US FDA and does not meet International Health Regulations requirements for a documented International Certificate. Contraindications include age under 6 months, symptomatic HIV with CD4 count under 200/mL, primary immunodeficiency, transplantation, immunosuppressive therapy, malignant neoplasia, thymic disorders with abnormal immune function, and hypersensitivity to components. Precautions include age 6 to 8 months, age 60 or older, asymptomatic HIV with CD4 count 200 to 499/mL, pregnancy and breastfeeding. Yellow fever vaccine-associated neurologic disease occurs at about 0.8 per 100,000 doses overall and 2.2 per 100,000 in people aged 60 or older; vaccine-associated viscerotropic disease at about 0.3 per 100,000 overall and 1.2 per 100,000 at age 60 or older, with a case-fatality of roughly 43%. In infants under 6 months the neurologic disease risk is estimated at 50 to 400 per 100,000, which is why vaccination is contraindicated below that age.^[9] Ten to thirty per cent of vaccinees report mild systemic symptoms for 5 to 10 days; anaphylaxis is 1.3 per 100,000 doses.^{[9] [10]}

Japanese encephalitis. Recommended by the Advisory Committee on Immunization Practices for people moving to an endemic country, longer-term (one month or more) travellers to endemic areas, and frequent travellers; consider for shorter stays with increased exposure. IXIARO (inactivated, Vero cell-derived) is licensed in the US: 0.25 mL intramuscularly at 0 and 28 days for ages 2 months to 2 years, and 0.5 mL at 0 and 28 days for ages 3 to 17 years and over 65; adults aged 18 to 65 can have the second 0.5 mL dose between 7 and 28 days after the first; complete the two-dose series at least one week before travel; booster at one year or later if risk continues. At about 6 years after booster, 96% of recipients remain protected.^[10] Pregnancy is a precaution and vaccination is generally deferred. Japanese encephalitis carries about 20 to 30% case-fatality and survivors have serious sequelae in 30 to 50%, which is the clinical argument for vaccination in exposed long-stay travellers.^[10]

Dengue vaccines. There is no dengue vaccine currently available in the United States. Globally, Dengvaxia was a three-dose live-attenuated vaccine for children aged 9 to 16 with laboratory-confirmed previous dengue infection living in endemic areas; it required prior infection, and the manufacturer discontinued it in 2024. Qdenga, a live-attenuated vaccine, requires two doses 3 months apart and is authorised in more than 40 countries; WHO has recommended it for ages 6 to 16 in settings of high dengue transmission intensity. TV003 is a single-dose candidate; preliminary phase 3 results showed 77% efficacy against virologically confirmed dengue after 3.7 years in seropositive recipients and 60% in seronegative recipients, and a licensed version was approved in Brazil in December 2025 for ages 12 to 59 before temporary suspension for safety review in June 2026. Travellers should follow the dengue vaccination recommendations of their own country's programme.^[4]

Chikungunya and Zika. Vaccine products are changing rapidly; where available they are used according to national policy. Prevention of these infections still rests on vector control and bite avoidance rather than on vaccination in most places.

There is no population screening programme for mosquito-borne viruses in the way there is for malaria. The practical equivalent is a travel and exposure history taken in every febrile illness, a low threshold for testing arboviruses in returning travellers, and obstetric follow-up when Zika exposure in pregnancy is suspected.

Pregnancy. Zika in pregnancy is the most serious special-group issue in this page: even asymptomatic maternal infection can damage the fetal brain and eyes, so any pregnant woman with possible exposure needs counselling, testing guidance and follow-up, and mosquito avoidance at home. Dengue in pregnancy is managed in hospital (Group B1 even without warning signs). Yellow fever vaccine is a precaution in pregnancy, and vaccination is reserved for situations where risk of exposure clearly outweighs risk from the vaccine. Japanese encephalitis vaccine is generally deferred. Pregnant travellers should be advised against unnecessary travel to areas with active outbreaks of Aedes-borne virus. Yellow fever vaccine is generally contraindicated in symptomatic HIV infection with CD4 count under 200/mL and is a precaution in asymptomatic HIV; pregnant women in this position need individualised counselling before travel.^[9][10]

Children. Yellow fever vaccine is not given under 6 months and is a precaution from 6 to 8 months. Dengue is severe more often in young children in some settings. Chikungunya is severe in neonates exposed around the time of birth. Japanese encephalitis occurs mainly in children in endemic areas, and the vaccine is approved from 2 months of age.^[9][10]

Older adults. Dengue and chikungunya are more severe with comorbidity; yellow fever vaccine is a precaution from age 60 because of increased risk of serious adverse events; West Nile neuroinvasive disease is largely a disease of older adults, with mortality of about 20% at age 70 or older against about 2% under 50.^[8][9]

Immunocompromised patients. Live yellow fever vaccine is contraindicated in significant immunosuppression; West Nile disease is more severe and prolonged; Japanese encephalitis vaccine may be given only after individualised assessment. Dengue management in these patients leans toward inpatient observation even without warning signs.

These infections are managed where tests and intensive care are scarce more often than where they are not, so what matters is what can be done with observation and fluids.

• Dengue is a clinical diagnosis in a febrile patient from an endemic area. A normal peripheral blood count can support it, but management must not wait for confirmation. Hospitalise anyone with warning signs or with comorbidity, and give oral rather than intravenous fluids whenever the patient can drink, reserving intravenous therapy for shock or inability to drink. Use paracetamol; avoid aspirin and NSAIDs. Use urine output and clinical perfusion rather than a laboratory trend if haematocrit is unavailable, but re-check haematocrit whenever possible and always watch for plasma leak. Avoid unnecessary prophylactic platelets and steroids. Mosquito nets and repellents for 3 weeks after the patient goes home protect the household. ^[3]
• Where chikungunya and dengue co-circulate, treat every suspected case as dengue first: no NSAIDs, aggressive fluids if shock, then reassess.
• In yellow fever, available intravenous fluids, avoidance of haemorrhage and mosquito isolation of the sick patient may be more valuable than any drug; refer to higher care early if bleeding or jaundice develops.
• For suspected encephalitis, supportive care, airway protection and access to lumbar puncture matter most; results often come late.
• Community vector control—clearing containers, covering water storage, screens and nets—outweighs individual counselling alone.

Plain-text related MedGrasp topics: malaria; encephalitis; acute fever in returning travellers; headaches; abdominal pain; rash in infection; thrombocytopenia; shock; pregnancy infection; vaccination and travel medicine; paediatric infections; infection control.