Anna Papa, MD, PhDAristotle University of Thessaloniki, Greece

Chikungunya

Figures of Makonde men

Chikungunya: Makonde word for “that which bends up” describing the appearance of the severe arthritis the infection causes to humans.

In Swahili it means "the illness of the bended walker”.

Chikungunya = that which bends up

CHIKV was first isolated in 1952 from the serum of a febrile patient in Africa following an outbreak on the Makonde Plateau, a border area between Mozambique and Tanzania.

Here are steep slopes and ridges on the side of the Makonde Plateau in Tanzania.The brachystegia woodland here is relatively undisturbed and has much biodiversity.

Makonde Plateau

Life cycle of CHIKV: sylvatic (primates – mosquitoes) & urban (humans – mosquitoes)

Copyright © 2015 Massachusetts Medical Society

Species name/classification: Aedes (Stegomyia) aegyptiCommon name: Yellow fever mosquito

A. aegypti is a known vector of several viruses including yellow fever virus, dengue virus, chikungunya virus and Zika virus.

CHIKV is carried mainly by the Aedes aegypti mosquitoes

Vectors of CHIKV

The adaptation of CHIKV to A. albopictus is a relatively recent event. During the

outbreak in the Indian Ocean (2005–2006) the virus has acquired a mutation at

residue 226 of the E1 glycoprotein, which allows it to infest A. albopictus. The

A226V mutation was demonstrated to increase viral fitness in the A. albopictus

vector and likely is the cause of the wide spread of the disease.

CHIKV particle and electron microscopic picture CHIK viruses

Chikungunya virus (CHIKV)Alphavirus genus, Togaviridae family

CHIKV small (about 60–70 nm in diameter), spherical, enveloped RNA virus

E1 glycoprotein participates in cell fusion (red orange) E2 glycoprotein binds to cellular receptors (yellow).

• CHIKV genome is single-stranded RNA molecule of positive polarity.

• It encodes 2 polyproteins — the nonstructural polyprotein, consistingof 4 proteins (nsP1, nsP2, nsP3, and nsP4), and the structuralpolyprotein, consisting of 5 proteins (capsid, E3, E2, 6K/TF, and E1).

• The 5′ end of the RNA molecule is capped with a 7-methylguanosine,and the 3′ end is polyadenylated.

• The envelope glycoproteins E1 and E2 play a role in attachment(fusion) and entry into the host cells.

CHIKV genome, 11.8-kb

Replication cycle of CHIKV in host cell

Rev. Med. Virol. 2011; 21: 78–88

1. Virions enter the host cells by fusion and

receptor mediated endocytosis in clathrin

coated vesicles.

2. The uncoating of the virions occurs in

the cytoplasm (site of mRNAtranscription and genome replication)

3. Early replication of RNA into mRNA and

translation of early regulatory proteins

4. Late replication of

RNA into mRNA &

translation of late

structural proteins

5. Assembly of structural proteins

and single stranded positive RNA,

virion maturation and release

Lum & Ng, 2015

Pathogenesis of CHIKV infection: viral dissemination and impact on host immune response

Copyright © 2015 Massachusetts Medical Society

PATHOGENESIS

active viral reservoir persists locally in the joints

Pathogenesis of CHIKV

It is likely that persistence of viral replication in synovial fluid is the cause of

chronic manifestations as determined by detection of viral RNA and antigen in the fluid, and by persistent serum elevation of IgM antibodies.

Incubation time: 2–6 d post-infection.

The hallmark of CHIKV infection is polyarthalgia, which lasts for few months to years

SIGNS AND SYMPTOMS

no antiviral treatment or licensed vaccine.

Acute phase: sudden high fever, severe joint pains (wrists, ankles or knuckles), muscle pain, headache, nausea, and maculopapular rash.

20-30% of the infected persons develop chronic disease: disabling polyarthritis.

Death is rare.

A morbilliform rash mostly non-pruritic, initially appearing in the upper limbs, is the most common cutaneous manifestation

Comparison of clinical features of CHIKV and DENV infectionsJoint pain and stiffness are more common with chikungunya than with dengue.

The diagnosis is usually clinical: acute fever + arthralgia: highly predictive of CHIKV infection in endemic areas

Lymphopenia, increased aspartate and alanine aminotransferases in blood,hypocalemia.

• Detection of CHIKV RNA in serum, blood, urine• Viral isolation during the first week of illness• Serology: Detection of IgM CHIKV antibodies from day 4–5

after the onset of illness.Increase of IgG CHIKV antibodies

Eighteen months after disease onset, 40% of patients still have anti-CHIKV IgM.

LABORATORY DIAGNOSIS

Viremia and immune response following CHIKV infection

3 CHIKV lineages • West African (WA)• Asian (and Asian/American sublineage) • East-Central-South African (ECSA) with Indian

Ocean (IOL) sublineage

Bordi et al. EID 2018

based on E1 gene sequences

No vaccine – No specific drug.

Symptomatic treatment

• Rest

• Prevent dehydration.

• Drugs (acetaminophen or paracetamol) to reduce fever and

pain.

• No aspirin and other non-steroidal anti-inflammatory drugs

(until dengue can be ruled out to reduce the risk of bleeding).

TREATMENT

CHIKV infection has been identified in over 60 countries in Africa, Asia,

Europe and the Americas (since 2013/2014).

2005-2006,major outbreak n the Indian Ocean.

2007, outbreak of autochthonous CHIKV infections for the first time in Europe (Italy 217 laboratory-confirmed cases). 2010 and 2014, autochthonous cases in France (two and 11 cases).December 2013, emergence of CHIKV - Asian genotype in the Caribbean (Saint Martin and the French West Indies) and quickly spread in

the Americas.

During 2017, autochthonous CHIK cases in France and Italy.

EPIDEMIOLOGY

CHIK reports to the Pan American Health Organization (PAHO) regional office

2014 more than 1 million suspected cases

2015, 693 489 suspected cases and 37480 confirmed cases.

Colombia bore the biggest burden with 356 079 suspected cases.

2016 349 936 suspected and 146 914 laboratory confirmed (half the

burden compared to the previous year). Countries reporting most

cases were Brazil (265 000 suspected cases), Bolivia and

Colombia (19 000 suspected cases, respectively).

2016 is the first time that autochthonous transmission of CHIK was

reported in Argentina following an outbreak of more than 1 000

suspected cases.

In the African region, Kenya reported an outbreak resulting in more

than 1 700 suspected cases.

2017, Pakistan continues to respond to respond to an outbreak which started in 2016.

WHO, up to April 2017

Figueiredo ML, Figueiredo LT.Rev Soc Bras Med Trop. 2014

Emergence of CHIKV in the Americas

France. By mid-September 2017, 9 autochthonous cases.

Genomic characterization identified an ECSA lineage strain, probably from the Central African region and carrying the A226V mutation facilitating transmission by

Ae. albopictus.

2017298 reported cases in Italy.

242 cases in Lazio (148 confirmed) 33 in Calabria (5 confirmed) 5 cases epidemiologically linked to Lazio in other Italian regions.

The virus belongs to the ECSA lineage and lacks the A226V mutation reported to increase replication in A. albopictus.

Need for strengthening mosquito surveillance in Europe in areas at risk of virus transmission.

GEOGRAPHICAL DISTRIBUTION

ECDC: The detection of clusters of autochthonous CHIK cases in

areas of Europe where A. albopictus is established is not

unexpected during the summer months, when environmental

conditions are favourable for mosquitoes. As the disease is

endemic in large areas of the intertropical zone, introduction via

viraemic traveller is possible.

The disease is notifiable at EU level

• Avoidance of mosquito bites

use of repellents (prefer-ably containing DEET)

wearing of long-sleeved shirts and long pants

use of screens, bed nets and air conditioning.

• Reduction of water puddles and containers (prevent mosquito

proliferation).

• Education of travelers to endemic areas about the risk, precautions and symptom recognition.

PREVENTION

CDC

If a mosquito bites an infected person during the 1st week of infection, it canbecome infected and spread the virus to other people through bites. To helpprevent others from getting sick, protection from mosquito bites is needed duringthe 1st week of illness.

PREVENTION of further virus spreadPatients should be protected from mosquito bites during the 1st week of illness to avoid spread of CHIKV to other people

viremia

Strengthening surveillance systems - clinician awareness- laboratory capacity for confirmation - rapid notification of cases

Regular review of contingency plans for mosquito-borne outbreaks

Education and cooperation of the general public on how to control mosquito breeding sites

Strengthened vector surveillance systems

Rapid implementation of vector control measures following each case.

CHIKV is an emerging arbovirus

Preparedness regarding CHIK in the EUrequires: