CHIKUNGUNYA FEVERObjectives

• Historical epidemiology of CHIKUNGUNYA• Regional scenario• What is CHKV • Clinical presentation• Vector borne diseases, Differential Diagnosis, Transmission• At risk groups ,Dengue /CHIKV dengue snapshot• Treatment

Francis Morey MD.MPHLorna Perez Surveillance Officer Epi-Unit

History (Its story)

A viral infection transmitted to humansBy the bite of an infected mosquitoIt has become endemic in south and central IndiaFirst outbreak in 1952 on the Makonde PlateauBorder between Tanganyika and MozambiqueFirst published report is from Africa in 1955 by Marion Robinson and W.H.R. LumsdenRecent large epidemic occurred in Malaysia in

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A disease of Africa and Asia

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INTRODUCTION

Caused by an Alpha Virus is a relatively rare form of viral fever ("debilitating non-fatal viral illness."

Spread by bite of Aedes aegypti mosquito which usually bite during day light hours.

the name is derived from Swahili word meaning “that which bends up”

Chikungunya (CHIK) virus first isolated from the serum of a febrile human in Tanzania in 1953.

Chik virus has caused numerous out breaks in Africa and South Eastern Asia, involving hundreds and thousands of people.

• Chikungunya is a Makonde word (one of the local languages in Tanzania) meaning

‘that which bends up’.

• Describes the posture patient assumes to relieve the severe joint pains

• Buggy Creek virus

Synonyms

• CHIKV Fever• Buggy Creek virus infection• Knuckle fever• Me Tri virus infection• Semliki Forest virus infection

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The Recent Epidemics

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African profile Asian profile

Current global profile

A226V-CHIKV

Humans

Peridomestic mosquitoesAe.aegyptiAe.albopictus

Focal urban outbreaks

Wild primates

Forest dwelling mosquitoes

Ae. furciferAe. taylori…

Humans

Sporadic casesFocal urban outbreaks

Humans

Peridomestic mosquitoesAe. albopictus

Ae.aegypti

Massive urban outbreaks

Simon F et al. Curr Infect Dis Rep 2011 (in press)

Notable Outbreaks

1963 to 1965 - An epidemic was reported in Calcutta – 4.37% of the people were later found to be seropositive 1973 – An epidemic 37.53% in Barsi - Sholapur district 2006 – Present epidemic after 33 years is the largest9,06,360 or more cases in Andhra Pradesh5,43,286 cases from Karnataka; 66,109 from B’loreMaharashtra 2,02,114 cases; Gujarat 2,500 casesTamil Nadu 49,567 cases; Orissa 4,904 cases, Madhya Pradesh 43,784 and Pune 138 cases

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Most Recent Epidemics

• Epidemic of CHIKV occurred in Malaysia – 1999• French island of Réunion in the Indian Ocean- 2005 • Epidemic was recorded in Mauritius – 2005• Madagascar, Mayotte and Seychelles – 2005• Hong Kong and Malaysia early 2006• Present indian epidemic is the largest -from Dec ’05• Maximum # of cases from Andhra Pradesh so far

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Chikungunya, 2005-2012, more than three millions cases ?

South of France, 09/20102 autochtonous cases

New Caledonia, 03/201133 autochtonous cases

Yemen - Saudi Arabia, 2010-11

Hundreds of cases

South China, 10/2010>10 cases

Reunion, 2010120 cases

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Why is this sudden epidemic ?

Analysis of the recent Indian epidemic has suggested that the increased severity of the disease is due to a change in the genetic sequence, altering the virus’ coat protein, which potentially allows it to multiply more easily in mosquito cells*.

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*http//medicine.plosjournals.org

Why is this quasi-pandemic ?

• Several distinct variants of the virus • A change at position 226 of the E1 coat protein• This A226V mutation caused the virus to more easily

invade and multiply in the mosquitoes• Three protein changes in non-structural proteins

– nsP1 (T301I), nsP2 (Y642N), and nsP3 (E460 deletion) – This mutant virus - from a neonatal encephalopathy

case

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Regional scenario

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CHIKUNGUNYA

The MOH/PAHO Belize request your Boarding pass

The CHIK Virus

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What is this virus ?

• Causative agent is an RNA – VIRUS• Class – Arbor Virus (Arthropod Borne) • Family – Togaviridae • Genus – Alpha Virus• Species – Chikungunya Virus• Similar to Semliki Forest Viruses (SFV) in Africa

and Asia.

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Epidemiological Triangle

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The HostThe Virus

The Environment

Interaction

The Vector

Vector Borne diseases• Mosquitoes• Aedes

– Dengue fever– Rift Valley fever– Yellow fever– Chikungunya

• Anopheles– Malaria

• Culex– Japanese encephalitis– Lymphatic filariasis– West Nile fever

• Sandflies• Leishmaniasis• Sandfly fever (phelebotomus fever)• Ticks• Crimean-Congo haemorrhagic fever• Lyme disease• Relapsing fever (borreliosis)• Rickettsial diseases (spotted fever and Q fever)• Tick-borne encephalitis• Tularaemia

• Triatomine bugs• Chagas disease (American trypanosomiasis)• Tsetse flies• Sleeping sickness (African trypanosomiasis)• Fleas• Plague (transmitted by fleas from rats to humans)• Rickettsiosis• Black flies• Onchocerciasis (river blindness)• Aquatic snails• Schistosomiasis (bilharziasis

Arbovirus (arthropod-borne virus) applies to any virus that is transmitted to humans and/or other vertebrates by certain species of blood-feeding arthropods, chiefly insects (flies and mosquitoes)

and arachnids (ticks)

• Bunyaviridae (comprising the bunyaviruses, phleboviruses, nairoviruses, and hantaviruses)• Flaviviridae (comprising only the flaviviruses)• Reoviridae (comprising the coltiviruses and orbiviruses)• Togaviridae (comprising the alphavirus)

Fever, malaise, headaches, myalgiasAdditional features: none Colorado tick fever Reoviridae (Coltivirus) Ticks

Dermacentor sp

Western US, western Canada

Phlebotomus fever Bunyaviridae (Phlebovirus) Sand flies

Phlebotomus sp

Mediterranean basin, Balkans, Middle East, Pakistan, India, China, eastern Africa, Panama, Brazil

Venezuelan equine encephalitis

Togaviridae (Alphavirus) Mosquitoes

Culex sp

Argentina, Brazil, northern South America, Panama, Mexico, Florida

Lymphadenopathy, rash Dengue fever Flaviviridae Mosquitoes

Aedes sp

Southeast Asia, West Africa, Oceania, Australia, South America, Mexico, Caribbean, US

West Nile fever Flaviviridae Mosquitoes

Culex sp

Africa, Middle East, southern France, Russia, India, Indonesia, US

Arthralgia, rash Chikungunya disease Togaviridae (Alphavirus) Mosquitoes

Aedes sp

Africa, India, Guam, Southeast Asia, New Guinea, limited areas of Europe

Mayaro virus Togaviridae (Alphavirus) Mosquitoes

Haemogus sp

Brazil, Bolivia, Trinidad

Hemorrhagic signs‡ Yellow fever Flaviviridae Mosquitoes

Aedes spp

Central and South America, Africa

Dengue hemorrhagic fever

Flaviviridae Mosquitoes

Aedes sp

Southeast Asia, West Africa, Oceania, Caribbean

Machupo virus Arenaviridae Rodent Bolivia

Junin virus Arenaviridae Rodent Argentina

Guanarito virus Arenaviridae Rodent Venezuela

Fever and CNS involvement

Eastern equine encephalitis

Togaviridae (Alphavirus) Mosquitoes

Culex sp

Atlantic and Gulf coasts of US, Caribbean, upper New York, western Michigan

Western equine encephalitis

Togaviridae (Alphavirus) Mosquito US, Canada, Central and South America

West Nile virus Flaviviridae Mosquitoes

Culex sp

Africa, Middle East, southern France, former Soviet Union, India, Indonesia, US

St. Louis encephalitis Flaviviridae Mosquitoes

Culex sp

US, Caribbean

Venezuelan equine encephalitis

Togaviridae (Alphavirus) Mosquitoes

Culex sp

Argentina, Brazil, northern South America, Panama, Mexico, Florida

La Crosse encephalitis Bunyaviridae Mosquitoes

Aedes spp.

North Central States, New York

Transmission

Reservoir – Non-human primates in AfricaNo animal reservoir is found in IndiaMaintained in nature by man – mosquito – man

cycleVector – Aedes aegypti, Ae. albapticus mosquitoSame vector as for Dengue and Yellow feversVehicle of transmission – NoneNo known mode - other than mosquito biteIncubation Period – 2 days to 12 days

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Main mode of transmission: mosquito bite

Other modes of transmission• Uncommon

– In utero transmission, can cause miscarriage in the 1st trimester

– Intra birth transmission, newborn of a viremic mother– Needle prick– Laboratory exposure

• Public Health Considerations– Blood transfusion– Organ or tissue transplant– No evidence of the virus in breast milk

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The Vector

Aedes aegypti mosquito, flight range < 100 metersAggressive daytime biter – under lights – bites anklesOnce infected – it has the virus until death (30 days)It is a man made mosquito – prefers its ownerBreeds in man made household containersIndoor, peridomestic, fresh water mosquitoMetallic, plastic, rubber, cement and earthen

containers - open, left or unused - get filled with waterAir coolers, ACs, Old oil drums, Over head tanks

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The Virus and its Vector The Criminal and It’s Accomplice

How Do Aedes Mosquitoes Transmit Diseases...

Mosquito bites and sucks blood containing the virus from an infected person.

Virus is carried in its body.

And passes the virus to healthy people when it bites them.

Attack Rates

• In urban localities it is more – why ?• Usual age group is above 15 years• Less common in children and infants• Family clustering of cases usual• Attack rates vary from 3 to 40% of population• Average attack rate is 10%• Herd immunity restricts further spread

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Aedes aegypti/albaptycus/Tiger mosquito

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Clinical Features

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CHIKV Infectiona disease of two phases

ACUTE PHASE•The majority of persons infected (72%‒97%) are symptomatic. •Incubation period: 3–7 days (range of 1‒12 days). •Main symptoms: acute onset of fever and polyarthralgia.

CHIKV Infectiona disease of two phases

CHRONIC PHASE• Early exacerbations,

inflammatory relapses, longstanding rheumatism and loss in quality of life

• More common in: – Those over 40 years old– Rheumatic or traumatic

history – High viral load

Simon F et al. Chikungunya virus infecion. Curr Infect Dis Rep DOI 10.1007/s11908-011-0180-1

CLINICAL FEATURES Acute viral infection of abrupt onset.

sudden onset of fever >38.5 degrees and severe arthralgia( ankle ,wrist, phalanges). Chills, flu like symptoms.

other constitutional symptoms like head ache, back pain, myalgia,photo phobia, retrorbital pain, conjunctival infection and rash. Nausea, vomiting, abd. pain, severe weakness

Incubation period is usually 1 to 12 days, symptoms ( average 4-7days).

Lasting for period of 7 to 10 days.

Rarely can result in meningo – encephalitis, Cardiovascular alt,death in elderly-weak immune system.

Chronic phase of severe arthralgia

Fever and polyarthralgia

• Fever– Acute onset– ≥38.5°C

• Joint pain– Sometimes serious and debilitating– Multiple joints– Bilateral and symmetric (usually)– Most commonly in hands and feet

http://www.paho.org/hq/index.php?option=com_docman&task=doc_download&gid=16985&Itemid=

Other signs and symptoms

• Headache• Myalgia• Arthritis• Conjunctivitis • Nausea and vomiting • Maculopapular rash

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Subacute stage, persisting distal inflamatory arthralgias

Simon F et coll. Medicine 2007;86: 123-37

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Subacute stage, tenosynovitis

43Simon F et coll. Medicine 2007;86: 123-37

Subacute stage, bursitis

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Subacute stage, associated rheumatic disorders

45Simon et al. Medicine 2007; 86 (3)

Peripheral vascular disorders

• Erythermalgia

• Raynaud’s syndrome

– High susceptibilty to the cold

– De novo and transient

– Commonly bilateral

– Associated with mixed cryoglobulinemia

The Arthralgia

• The small joints of the lower and upper limbs• Migratory poly arthralgia – not much effusions• Larger joints may also be affected (knee, ankle)• Pain worse in the morning – less by evening• Joints may be swollen & painful to the touch• Some patients have incapacitating joint pains• Arthritis may last for weeks or months.

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Kun gunyala

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The Contorted Posture

Skin Rash in Dengue CHIKV

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Rare Clinical Features

• A petechial or maculo papular rash usually involving the limbs may occur.

• Hemorrhage is rare • Nasal blotchy erythema, freckle-like

pigmentation over centro-facial area, • Flagellate pigmentation on face and extremities• Lichenoid eruption and hyper pigmentation in

exposed areas

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Rare Clinical Features

Multiple aphthous-like ulcers over scrotum, crural areas and axilla

Unilateral or bilateral lympoedema of the limbsLymphadenopathy not commonMultiple ecchymotic spots in children Vesiculo-bullous lesions in infants and Sub-ungual hemorrhagesSevere menigo-encephalitis – rare; may be fatal

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Course of Illness

Fever typically lasts for 2 - 3 days and comes downFever may reoccur after 3 days – ‘saddle back’ feverSome rare cases - fever lasts up to a couple of weeksPatients do have prolonged fatigue for several weeks High fever & crippling joint pain marked this epidemicJoint pain, intense headache, insomnia and an extreme

degree of prostration may last for 5 to 7 daysLife long immunity, once one suffers this infection

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Who are at greater risk ?

• Pregnant women• Elderly people• Newborns• Women in general• Diabetics• Immuno-compromised patients• Patients with severe chronic illnesses

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CHIKV Morbidity

• Chikungunya is a self-limiting illness • Causes of prolonged morbidity are

– Severe dehydration – Electrolyte imbalance and – Loss of glycemic control

• Recovery is the rule • In about 3 to 5%

– Incidence of prolonged arthritis

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Mortality

• A few deaths have been reported - Examples• It was thought to be due mainly to

– Inappropriate use of antibiotics and NSAIDs – Virus can cause thrombocytopenia – These drugs can cause gastric erosions - thus – Leading to fatal upper GI bleed – Use of steroids for the joint pains &

inflammation– This is dangerous and completely unwarranted

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Outcome

• Acute symptoms: resolved in 7-10 days• Mortality: rare (elderly)• Some patients have relapses of rheumatic

symptoms in the months following the acute illness

• Chronic illness of varying degrees, with pain persisting for months or years

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DIAGNOSIS

Suspect Case

Characteristic triad of fever, rash and rheumatic manifestations

Probable Case

As above with positive serology from single sample

Confirmed Case

A probable case with any of the following

Four fold HI antibody difference in paired serum samples.

Detection of IgM antibodies.

Virus isolation from serum.

Detection of Chikungunya virus nucleic acid in sera by RT - PCR

Laboratory• Transient lymphopenia• Thrombocytopenia (early and

moderate)

• C-reactive protein elevation• Elevated liver

transaminases

Risk factors for severe disease

• Infant exposure during birth• Elderly (>65 y.o.) • Medical history (e.g., diabetes,

hypertension, or cardiovascular disease)

WHO case definitions

Algorithm for suspected CHIKV CASE

Epidemiological scenario: First introduction of virus in a specific area 1

This algorithm is intended to be followed by those reference laboratories with established capacity for CHIKV detection.

Samples should be processed taking into account the number of days after the onset of symptoms. If the sample was taken between 1 and 8 days after the onset of symptoms, then it will be processed for both RT-PCR and IgM serology.

Samples should be coming from suspected cases, defined as “A patient with acute onset of fever > 38.5 C (101.3 F) and severe arthralgia or arthritis not explained by other medical conditions, and who resides or visit epidemic or endemic areas within two weeks before the onset of the symptoms”.2

1 As of December 2013, it applies for Caribbean countries and territories where the CHIKV still has not been detected, as well as Latin American Countries. 2 CDC/PAHO. Preparedness and Response for Chikingunya Virus Introduction in the Americas. 2011

Algorithm Dengue/CHIKV

Pregnancy and CHIKV

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Pregnancy and CHIKV

• Mother to fetus transmission can occur• Reported between 3 to 4.5 months of gestation• Maternal IgG develops in 2 weeks after CHIKV• This passes through placenta – confers protection• Intra-partum risk is 48% if mother has viremia• Neonatal infections are very mild; fully recover• No miscarriages or congenital malformations

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Pregnancy - CHIKV

June 2005 to Jan 2006, 84 pregnant women with CHIKV

In 88% cases the newborns are asymptomatic10 newborns had severe attacks, 4 meningo-

encephalitis3 with intravascular coagulations; No infants diedOne case of severe intra cerebral hemorrhage Had severe thrombocytopenia All confirmed by specific serology or PCR or bothWomen had severe intra-partum viremia & fever

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Differential Diagnosis

• Dengue fever, DHF, DSS• O’nyong-nyong viral fever• Sindbis viral fever• Other non specific viral fevers• Any other acute fever like malaria, UTI etc.

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MALARIA

DENGUE FEVER

CHIKUNGUNYA FEVER

Jaundice Renal failure

Fever

Myalgia

RashBleedings

Retro-orbital pain

Transient arterial hypotension

Acute polyarthritis Tenosynovitis

Anemia

LEPTOSPIROSIS

Adapted from Simon et al, Schwartz, Infections in travelers, Ed 2009

BACTERIALSEPSIS

MyalgiaMyocarditis

ADRS

Chikungunya outbreak, high risk for misdiagnosis

Dengue and CHIK

• Virus transmitted by the same mosquitos

• Similar clinical picture• The viruses can circulate in the same

areas–- co-infection• Discarding dengue is important, for an

adequate clinical care that improves the prognosis of dengue

Differential DiagnosisFeature CHIKV DENGUE

Presentation A+F ± mild rash

A+F+Rash

Arthralgia Moderate Severe

Arthritis Not common Frequent

Bone pains None Break bone fever

Thrombocytopenia

Mild (Not < 1K)

May be severe

Hemorrhage None May be present

Shock syndrome

Never May occur

Immunity (IgG) Life long 2nd attack fatality

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Table 1: Total number of Febrile cases positive for Dengue per District for 2014

District Confirmed probable clinical Suspected TotalWHO case definition

% dengue of febrile cases

% District febrile cases

Corozal 3 5 7 76 91 15 16.5 11.0

Orange Walk 0 1 0 13 14 1 7.1 1.7

Belize 9 16 22 346 393 47 12.0 47.4

Cayo 8 6 6 142 162 20 12.3 19.5

Stann Creek 6 3 2 87 98 11 11.2 11.8

Toledo 6 0 1 63 70 7 10.0 8.4

Unknown 0 0 0 1 1 0 0.0 0.1

Total 32 31 38 728 829 101 12.2 100.0

Laboratory description of Dengue Test

Test description Rapid test requested Eliza test Requested Total percent

Test requested 644 282 926 100.0

Test Done 622 242 864 93.3

RESULTS IgM positives NS1 positives Total IgM/NS pos

Total positive test 32 40 72 100.0

positivity rate % 5.1 16.5 8.3 91.7 negative

Treatment of CHIKV

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CHIKUNGUNYA DRUG France develops a new drug to treat

"We are confident today that a drug to treat Chikungunya will be made available and we are hopeful that this drug will be available at the very end of this year or at the very start of 2007"

- French Health Minister - Xavier Bertrand- September 11th 2006

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Treatment• There is no specific treatment for CHIKV• No vaccine or preventive pill is available • The illness is usually self-limiting• It will resolve with time over a week to 10

days• No relapses occur – no second attacks • Convalescence may take longer• Symptomatic treatment only

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Treatment

Rest to the patient and mild movements of jointsCold compresses to inflamed jointsLiberal fluid intake or IV fluidsAnalgesics and NSAIDS

Paraetamol ± Ibuprofen or aceclofenac or diclofenac

Naproxen sodium (Naprasyn, Xenobid)Aspirin should be avoided

Hydroxy chloroquine sulphate (HCQS) 200 mg/odChloroquine phosphate 250 mg/od

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What not to give ?

• No indication for antibiotics• Never use costly, large spectrum drugs• No indication for long acting steroids• No indication for short term steroids also

in the acute phase of illness• Rarely, if the joint swelling persists – we

may consider use of steroids in short burst.

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Management of cases

• Rest in bed will help hasten recovery• Infected persons should be protected

– from further mosquito exposure – staying indoors and/or under a mosquito net– during the first few days of illness– This is to reduce transmission to others

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The Virus and its Vector The Criminal and It’s Accomplice

CHIKUNGUNYA