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CHIKUNGUNYA FEVER

Dr. R.V.S.N.Sarma., M.D., M.Sc., (Canada)

Consultant Physician and Chest Specialist

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Updated until 23rd September 2006

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What is this tongue twister ?

• It is CHIKUNGUNYA• To be pronounced as [chick’-en-GUN-yah]• It is not written as CHICKEN GUINEA• Nothing to do with chicken or mutton eating• Derived from the Makonde verb - Kun gunyala• In Swahili it means ‘to become contorted’ or • More specifically as ‘that which bends up’• Refers to the stooped posture of the patient

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Synonyms

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

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Blessed are we !!• This is not a Dengue epidemic !• This is not the SARS which stole all the show !!• This is not Bird-Flu hitting Indian economy !!!• This is not the Plague epidemic which

threatened to sweep our country !!!!• Above all - it is not like HIV or Hepatitis B !!!!!• This is a self limiting, non fatal viral illness –

Thanks to the Almighty

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Should we be panicky ?• A common viral fever• Self limiting – non fatal illness• Fever, myalgia, arthralgia, lasting 2 - 7 days• Should give big name for it and be panicky ?• Should create such media hype and chaos ?• Above all, should we politicize to this extent?

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CLINICAL EPIDEMIOLOGY

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A disease of Africa and Asia

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Asian Distribution

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Epidemiological Triangle

The HostThe Virus

The Environment

Interaction

The Vector

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History (Its story)• A viral infection transmitted to humans• By the bite of an infected mosquito• It has become endemic in south and central

India• First outbreak in 1952 on the Makonde Plateau• Border between Tanganyika and Mozambique• First published report is from Africa in 1955 by • Marion Robinson and W.H.R. Lumsden• Recent large epidemic occurred in Malaysis in

1999

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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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Chikungunya Virus - EM

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Transmission• Reservoir – Non-human primates in Africa• No animal reservoir is found in India• Maintained in nature by man – mosquito –

man cycle• Vector – Aedes aegypti, Ae. albapticus

mosquito• Same vector as for Dengue and Yellow fevers• Vehicle of transmission – None• No known mode - other than mosquito bite• Incubation Period – 2 days to 12 days

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The Vector

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The Vector• Aedes aegypti mosquito, flight range < 100 meters• Aggressive daytime biter – under lights – bites

ankles• Once infected – it has the virus until death (30

days)• It is a man made mosquito – prefers its owner• Breeds in man made household containers• Indoor, peridomestic, fresh water mosquito• Metallic, plastic, rubber, cement and earthen

containers - open, left or unused - get filled with water

• Air coolers, ACs, Old oil drums, Over head tanks

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Aedes aegypti

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Aedes albaptycus

Tiger Mosquito

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Madam Aedes - at her Lunch

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Water tap – A disease trap

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Open Overhead Tanks

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Domestic Water Collections

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Why only Aedes Mosquito ?

• Scanning Electron Micro-graph of the mid gut cells of the mosquito

• Location of the Chik Virus binding proteins.

• Not transmitted to the progeny of the mosquito

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The Recent Epidemics

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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 largest• 9,06,360 or more cases in Andhra Pradesh• 5,43,286 cases from Karnataka; 66,109 from B’lore• Maharashtra 2,02,114 cases; Gujarat 2,500 cases• Tamil Nadu 49,567 cases; Orissa 4,904 cases, • Madhya Pradesh 43,784 and Pune 138 cases

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Distribution in India• The disease is common with periodic epidemics • Sporadic outbreaks described in Madras and Vellore• Cases were reported in Chennai, Pondicherry, Vellore • Vizag in 1964; Rajahmundri, Kakinada, Nagpur in

1965 • The last epidemic in India was in 1973• From Yavat village (Pune) in 2000• 2.9% in the Andaman & Nicobar Islands are

seropositive• Infected mosquitoes seen in Pune, Maharastra State

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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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The Indian Epidemic• Present epidemic has started in Nov 2005• Andhra Pradesh, Karnataka, Maharashtra,

Madhya Pradesh, Orissa, Gujarat, Tamilnadu, Rajasthan, Kerala are under its onslaught

• This is spreading far and wide at a rapid rate

• Not much spread to the northern states like Delhi, Haryana, Punjab as yet.

• Not much cry from U.P. and Bihar

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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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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*. *http//

medicine.plosjournals.org

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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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Clinical Features

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Symptoms

• Sudden onset of fever, chills • Headache, nausea, vomiting,

abdominal pain• Joint pain with or without swelling,• Low back pain and rash • Very similar to those of Dengue but • Unlike in Dengue, no hemorrhagic or

shock syndrome

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Clinical Features• Incubation period is 2-12 d; usually 3-7 days• Viremia last for 5 days (infective period)• Silent CHIKV – inapparent infections in children• Flu-like symptoms, Severe headache and chills • High grade fever (40°C or 104°F), • Arthralgia or arthritis – lasting several weeks• Conjunctival suffusion and mild photophobia• Nausea, vomiting, abd. pain, severe weakness

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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

The Contorted Posture

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Acute CHIKV Fever

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Skin Rash in Dengue

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Skin Rash in CHIKV

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Petechiae on feet

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The Burden of 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

limbs• Lymphadenopathy not common• Multiple ecchymotic spots in children

• Vesiculo-bullous lesions in infants and • Sub-ungual hemorrhages• Severe menigo-encephalitis – rare; may be

fatal

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Course of Illness• Fever typically lasts for 2 - 3 days and comes down

• Fever may reoccur after 3 days – ‘saddle back’ fever

• Some rare cases - fever lasts up to a couple of weeks

• Patients do have prolonged fatigue for several weeks

• High fever & crippling joint pain marked this epidemic

• Joint pain, intense headache, insomnia and an extreme degree of prostration may last for 5 to 7 days

• Life 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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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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Vertical TransmissionVertical maternal-fetal transmission of the Chikungunya virus. Ten cases in newborns among 84 pregnant women

Robillard PY, Boumahni B, Gerardin P, Michault A, Fourmaintraux A, Schuffenecker I, Carbonnier M, Djemili S, Choker G, Roge-Wolter M, Barau G.

Pub Med. 2006 May; 35(5 Pt 1):785-8.

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Pregnancy - CHIKV• June 2005 to Jan 2006, 84 pregnant women with

CHIKV

• In 88% cases the newborns are asymptomatic

• 10 newborns had severe attacks, 4 meningo-encephalitis

• 3 with intravascular coagulations; No infants died

• One case of severe intra cerebral hemorrhage

• Had severe thrombocytopenia

• All confirmed by specific serology or PCR or both

• Women 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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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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Laboratory Diagnosis

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Laboratory Diagnosis

1. Four fold or more rise of HI Antibody2. IgM capture ELISA using MAbs3. Indirect Immuno Flourescence Test (I

IFT)– On infected cells from tissues

4. Virus Isolation – Infant Swiss Albino mice– Vero BHK-21 cell lines are used

5. Nucleic acid amplification by PCR & RT PCR

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Laboratory Diagnosis• IgM capture ELISA – Good serological

test• Not commercially available• NIV – Pune, NICD – Delhi only• Positive after 5-10 days & lasts up to 6

months• HI Antibody appears on day 3 or 4• RT –PCR confirmatory – before the 5th day

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Value of RT -PCR• Real Time PCR scores over conventional PCR• Positive in the phase of viremia – up to 5 days• Transportation of sample to be at 2o to 8o c• It is a confirmatory test with high specificity• Its sensitivity is very high; detects even 1 copy• After the viremia ceases – it will be negative• We do not have the HI Ab or Ig M capture

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Treatment of CHIKV

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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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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• Rest to the patient and mild movements of joints• Cold compresses to inflamed joints• Liberal fluid intake or IV fluids• Analgesics and NSAIDS

– Paraetamol ± Ibuprofen or aceclofenac or diclofenac

– Naproxen sodium (Naprasyn, Xenobid)– Aspirin should be avoided

• Hydroxy chloroquine sulphate (HCQS) 200 mg/od

• Chloroquine 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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A Y U S H• A Ayurvedic or Acupuncture• Y Yoga and or Naturopathy• U Unaani• S Siddha• H Homeopathy

No comments on these alternative medicines

If no pathy works, finally Venkatapathy or Tirupathy

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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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Pregnancy and Lactation

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NSAIDs in Pregnancy• Using NSAIDs during early or late stages of

pregnancy is not associated with congenital anomalies, prematurity, or low birth weight, but

• There is a significant link between NSAID use and miscarriage in the first trimester.

• In third trimester may cause premature delivery

• Recommend stopping NSAIDS 6 to 8 weeks before delivery to prevent premature closure of fetal ductus arteriosus.

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Lactating WomenQ. Can a woman suffering from early signs of

Chikungunya breast feed her month old baby?A. It is better if you do not. During very early

stages fever there is viremia. And some of the virus may be present in the breast milk. As in newborns the immune system is not mature particularly monocyte-macrophages system, these cells may not be able to take care of the ingested virus absorbed through mucous membranes.

Answered on 28 August 2006 by Dr. Pradeep SethProfessor of Virology and Head, Department of Microbiology

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Prevention of Mosquito bite

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Avoid Mosquito Menace

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Prevention from mosquito bites

• Use insect repellent such as DEET on exposed skin.

• Wear long sleeves & pants, treat clothes with permethrin

• Have secure screens on windows and doors

• Get rid of mosquito breeding sites by

– Emptying standing water from flower pots, buckets etc.,

– Change the water in pet dishes in bird baths weekly

– Drill holes in tire swings so water drains out

– Keep children's wading pools empty

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Perfect Protection

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Vector Control Measures• Cover all tanks, cisterns, barrels, containers• Remove old tyres, tins, buckets and bottles• Clogged gutters and drains need to be cleared• Change water in dip trays, plant pots twice week• Tanks need to be covered and cleaned - 2 weeks• Weeds and tall grass to be cut short – ↓ hiding• Temephos 1 ppm for large water tanks

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Correct leaking taps

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Cover overhead tanks

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Domestic Water Collections

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Properly close the garbage bins

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Peri domestic fumigation

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Out door fumigation

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Mosquito Magnet

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IEC Activities• Awareness of CHIKV• Mass media, TV, Radio, News

papers• Awareness of vector and its control• Involvement of NGOs• Special campaigns• Punishment for non-compliance