Chikungunya by Dr Sarma

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Chikungunya by Dr Sarma Powered By Docstoc
					Updated until 23rd September 2006


       Dr. R.V.S.N.Sarma., M.D., M.Sc., (Canada)
          Consultant Physician and Chest Specialist

                                                          1   2
                 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                                           3
      •    CHIKV Fever
      •    Buggy Creek virus infection
      •    Knuckle fever
      •    Me Tri virus infection
      •    Semliki Forest virus infection                              4
                    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                                                5
                 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?                                               6

                 A disease of Africa and Asia                                  8
                 Asian Distribution                        9   10
                 Epidemiological Triangle
                        The Environment
                                    The Vector


                 The Virus                 The Host                                        11
                     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                                                 12
The CHIK Virus

                    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.                                          14
                 Chikungunya Virus - EM                            15
      •    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                                                  16
The Vector

                         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                                                      18
                 Aedes aegypti                   19
                 Aedes albaptycus

                    Tiger Mosquito                       20
                 Madam Aedes - at her Lunch                                21
                 Water tap – A disease trap                                22
                 Open Overhead Tanks                         23
                 Domestic Water Collections                                24
                 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                               25
The Recent Epidemics

                      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                                                        27
                    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                                                      28
                 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                                                 29
                 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                                            30
                        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                                             31
                 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//                                                32
                 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                                                          33
Clinical Features

      •    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                                          35
                      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                                                36
                       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.                                                37
                 Kun gunyala

                       The Contorted Posture                                 38
                 Acute CHIKV Fever                       39
                 Skin Rash in Dengue                         40
                 Skin Rash in CHIKV                        41
                 Petechiae on feet                       42
                 The Burden of CHIKV                         43
                 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                                              44
                 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                                            45
                   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                                                 46
                 Who are at greater risk ?
      •    Pregnant women
      •    Elderly people
      •    Newborns
      •    Women in general
      •    Diabetics
      •    Immuno-compromised patients
      •    Patients with severe chronic illnesses                                      47
                  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                                   48
      • 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                                                  49
Pregnancy and CHIKV

                 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                                                 51
                   Vertical Transmission
             Vertical 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.                                                   52
                  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                                                   53
                  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.                                            54
                 Differential Diagnosis
        Feature            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                                                     55
Laboratory Diagnosis

                     Laboratory Diagnosis
     1. Four fold or more rise of HI Antibody
     2. IgM capture ELISA using MAbs
     3. 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                                       57
                  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                                               58
                     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                                                 59
Treatment of CHIKV

      •    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                                                61
                  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
                    - French Health Minister - Xavier Bertrand
                                      - September 11th 2006                                                   62
      •    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                                                      63
                  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.                                          64
      •   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                                         65
                   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                                              66
Pregnancy and Lactation

                 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.                                                  68
                     Lactating Women
      Q. 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 Seth
                 Professor of Virology and Head, Department of Microbiology   69
Prevention of Mosquito bite

                 Avoid Mosquito Menace                           71
           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                                                          72
                 Perfect Protection                        73
                 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                                                74   75
                 Correct leaking taps                          76
                 Cover overhead tanks                          77
                 Domestic Water Collections                                78
             Properly close the garbage bins                                 79
                 Peri domestic fumigation                              80
                 Out door fumigation                         81
                 Mosquito Magnet                     82
                      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                                    83

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