Chikungunya virus: Questions

The virus is taken up by clathrin-mediated endocytosis, and the acid endosome triggers E1 to form fusion trimers that merge the membranes.

Fusion is low-pH dependent rather than neutral-pH, is driven by E1 rather than the capsid or 6K, and alphaviruses do not inject their genome.

Most chikungunya infections are symptomatic, unlike dengue and Zika, though up to a quarter are subclinical or asymptomatic.

It is not silent in most people, is not restricted to children or to reinfection, and only a minority develop chronic arthritis.

The 5’ two-thirds of the positive-sense genome is translated directly into the nonstructural polyprotein (nsP1 to nsP4); the structural proteins come from a separate subgenomic messenger RNA.

The genome is non-segmented and positive-sense, so there is no virion polymerase and no one-protein-per-segment arrangement.

Most South African cases are imported by travellers, but Aedes aegypti is present in parts of the country, so a viraemic case could seed local transmission.

It is not endemic like the local alphavirus Sindbis, is not tick-borne, is not excluded by a lack of vector, and is an arthritic rather than encephalitic illness.

Reverse-transcription PCR on blood detects viral RNA during the high-titre viraemia of the first week; IgM becomes useful from about day five.

IgG marks past infection, culture from joint fluid is usually negative, and there is no routine urinary antigen test.

Chronic joint symptoms, affecting on the order of 40% of adults, are predicted by older age, female sex, severe acute illness and high acute viral load.

Young age, mild disease and vaccination all make persistent arthralgia less likely.

On Reunion the epidemic infected roughly a third of the population and selected the E1-A226V mutation that adapted the virus to Aedes albopictus.

It spread well beyond mainland Africa to India and Southeast Asia, remained mosquito-borne, and left substantial chronic arthralgia.

Mxra8 is used by the arthritogenic Old World alphaviruses, chikungunya, o’nyong-nyong, Ross River and Mayaro viruses, a molecular correlate of the rash-and-arthritis clade.

It has no role for the encephalitic New World alphaviruses, and the flaviviruses and phleboviruses use unrelated entry factors.

Chikungunya presents with high fever, severe symmetrical polyarthralgia and a maculopapular rash in around 80% of patients.

Jaundice and bleeding suggest a haemorrhagic fever, encephalitis and paralysis suggest an encephalitic arbovirus, and the other pictures point elsewhere.

E1-A226V improved viral fitness in Aedes albopictus, a hardier and more temperate mosquito, extending the virus’s potential range.

It did not alter antiviral susceptibility, attenuate the virus, remove the vector requirement, or enable tick transmission.

The name is a Makonde word for the contorted, stooped posture that severe joint pain forces, from the 1952 epidemic on the Makonde Plateau of what is now Tanzania.

The other options describe real features of the illness but none is the origin of the name.

The incubation period is about two to twelve days, most often three to seven, after which fever and arthralgia begin abruptly.

The other intervals are far too short or too long for chikungunya.

A mother who is viraemic around the time of delivery transmits to the newborn in roughly half of cases, causing a severe neonatal encephalopathy.

Early-pregnancy infection, chronic arthralgia, pre-existing immunity and breastfeeding are not the main route of peripartum vertical transmission.

Viral RNA and antigen persist in synovial macrophages and fibroblasts, sustaining local inflammation with interleukin-6 and other mediators.

Radiographs usually show soft-tissue swelling rather than destruction, and the mechanism is not autoantibody, bacterial infection or classic immune-complex deposition.

nsP4 is the RNA-dependent RNA polymerase.

nsP1 caps the RNA and anchors the replication complex, nsP2 is the protease and helicase, nsP3 is a virulence and host-range determinant, and capsid is a structural protein.

Aedes aegypti and Aedes albopictus sustain the urban cycle, and human viraemia is high enough to infect them, so no animal reservoir is needed for an epidemic.

Anopheles transmit malaria, Culex and Culiseta transmit encephalitic arboviruses, and Psorophora are equine-encephalitis vectors.

Ixchiq, approved in late 2023, was the world’s first licensed chikungunya vaccine, a live-attenuated single-dose product; a virus-like particle vaccine, Vimkunya, followed.

Vaccines are not limited to inactivated designs, do not remove the need for bite avoidance and vector control, and are for adults and adolescents rather than young infants.

Viraemia is high, correlates with disease severity, and neutralising antibody to E2 mediates recovery and confers durable, probably lifelong, immunity.

Viraemia is neither low nor irrelevant, immunity is durable rather than brief, and antibody rather than cytotoxic T cells alone is the principal protective arm.

E2 is the attachment protein and the dominant target of neutralising antibody, while E1 carries the fusion peptide.

E3 chaperones the E2 precursor and is cleaved by furin; the capsid forms the internal nucleocapsid, not the surface spikes.

O’nyong-nyong virus causes a near-identical fever, arthralgia and rash syndrome and is chikungunya’s closest relative, separated serologically and by its prominent cervical lymphadenopathy.

Dengue and Zika share the setting but favour myalgia; Ross River is a more distant arthritogenic alphavirus; West Nile is an encephalitic flavivirus.

Until dengue is excluded, paracetamol is preferred because non-steroidal anti-inflammatory drugs and aspirin carry a bleeding risk in dengue.

There is no chikungunya antiviral to interact with, these drugs do not worsen arthralgia, none clears the virus, and they become the mainstay for chikungunya arthralgia once dengue is excluded.

Chikungunya is an Old World arthritogenic alphavirus, causing fever, rash and polyarthritis.

The New World alphaviruses (eastern, western and Venezuelan equine encephalitis) are classically encephalitic, and the flaviviruses and phleboviruses are separate genera.