Transcript Epidemiology of Rabies

‫بسم هللا الرحمن الرحيم‬
Clinical Epidemiology of
Rabies
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Definition
History
Etiology
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Definition
• A fatal viral disease (encephalomyelitis)
• In human and most other mammals
• One of the most common viral causes of
mortality
• 15 million people annually receiving
post-exposure vaccination to prevent
the disease .
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Definition
• 55000-100000 deaths occur each year
because of rabies.
• Rabies is a neglected disease of
poor and vulnerable populations
whose deaths are rarely reported.
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Etiologic agent
• Rabies virus
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Genus : Lyssavirus (lyssa: rage in Greek)
Family : Rabdoviridae family
Enveloped bullet-shaped virus
5 structural proteins
SS RNA, non-segmented
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Rabies Virus
Rabies virus particles
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Rabies Virus in the
Environment
•Normally, rabies virus cannot live
long in a warm, putrefied
environment,
• Survives in the body less than 24
hours after death.
•A few minutes in direct sunlight
will inactivate rabies virus.
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Rabies Virus in the
Environment
• under cool conditions (in refrigerator) it
may live for many days
• If the virus is frozen at -70oC, it can live
for years.
• Rabies virus is no longer active in
dried saliva
• Is killed by bleach, ethyl alcohol, soap,
detergent, and quaternary ammonium
compounds.
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Pathogenesis of Rabies
Widespread CNS involvement
Spreads to the CNS in the
endoneurium of the Schwann cells
Enters the peripheral nerves through
the neuromuscular junction
Inoculation, the virus
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replicates in the striated or connective tissue
Pathogenesis of Rabies
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Descriptive
epidemiology
and
occurrence
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Clinical epidemiology of Rabies
Definition and public health importance
Etiologic agents
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Incubation period
Natural couarse
Geographical distribution
Timeline trend
Age, Gender, Occupation, Social situation
Predisposing factors
Susceptibility & Resistance
Secondary attack rate
Modes of transmission, period of communicability
Prevention : primary, secondary, tertiary
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1 -Incubation Period
• 4 days or 19 years (rarely)
• Average : 30-90 days
Depends on:
Wound severity
Wound site (nerve supply)
Distance from the brain
Amount & strain of virus
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‫محدوده دوره كمون هاري‬
‫‪14‬‬
2 - Natural course
Stage
Duration
Incubation period
< 30 days (25%)
30-90 days (50%)
90-365 days (20%)
> 365 days (5%)
Prodrome & early symptoms
2-10 days
Acute neurologic disease
Furious rabies (80%)
Paralytic rabies (20%)
2-7 days
2-7 days
Coma, Death
0-14 days
Recovery
Very rare
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Natural course
Exposure (usually from contaminated saliva through animal bites)
Incubation
30-90 days
Prodromal symptoms (fever, chills, malaise, fatigue,
insomnia, anorexia, headache, anxiety and irritability)
Up to 10 days
Local Neurologic symptoms (pain, paresthesias,
weakness)
Classic (encephalitic) rabies symptoms -80% cases
Paralytic rabies -20% cases
Coma, Death ~~~ 100%
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Rabies/clinical manifestations
• 5 phases of illness
• First phase: asymptomatic
• Second (prodromal) phase
• Third phase: neurologic signs
• Forth phase : coma, death
• Fifth phase : recovery
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Rabies/clinical manifestations
• First phase: asymptomatic
• Virus IP: 10-90 days (4d-19yr)
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Rabies/clinical manifestations
• Second (prodromal) phase
• 2-10d
• Viral invasion of CNS (limbic system,
spinal cord, brain stem)
• Respiratory symptoms
• Gastrointestinal symptoms
• Behavioral & emotional symptoms
• Local pain itching, (50%)
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Rabies/clinical manifestations
• Third phase: neurologic signs
• Widespread infection of the brain
• “Furious”:
Aggressiveness, biting, yelling, hallucinating
Triggered by sensory stimuli
Hydrophobia
Aerophobia
Violent diaphragmatic contractions
Hyper-reflexia, cholinergic manifestations
lacrimation, salivation, mydriasis, pyrexia
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Rabies/clinical manifestations
• Forth phase: coma, death
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Extensive cortical virus spread
Death usually in 7 days
Respiratory arrest
Myocarditis
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Rabies/clinical manifestations
• Fifth phase: recovery
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Rare survivors
Atypical presentations
1972: bat related, dysarthria, hemiparesis
1976: dog bite, quadreparesis,myoclonus,
cerebellar signs,frontal lobe signs
• 1977: Lab worker, aerosol exposure to highly
concentrated fixed rabies virus
• 1992-1995: 4 Mexican children (3:dog, 1:
vampire bat), received vaccine, no Ig
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Non-Classical Rabies/clinical
manifestations
• Neuropathic pain, radicular pain, objective
sensory and motor deficits
• Choreiform movements of the bitten limb
during prodromal phase
• Focal brain stem signs, myoclonus
• Hemiparesis, hemisensory loss, ataxia, vertigo
• Seizures, ataxia
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Rabies/Differential Diagnosis
• Meningitis/Encephalitis: Japanese, eastern
equine, West Nile V., enterovirus 71, Nipah V.
• Epilepsy
• Drug toxicity
• Acute hepatic porphyria, neuropsychiatric
disturbances
• Substance abuse, acute serotonin syndrome
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3 – Geographical distribution
• Rabies occurs in more than 150
countries and territories
• Worldwide, more than 55 000
people die of rabies every year
mostly in Asia and Africa.
• 40% of people who are bitten by
suspect rabid animals are
children
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Fact Sheet N°99, July 2014
‫‪3 – Geographical distribution‬‬
‫• در ‪ 44‬كشور يا منطقه به مرحله حذف رسيده و‬
‫موردي گزارش نشده است‬
‫• قطب جنوب و تعدادي از جزاير‪ ،‬در ساير مناطق‬
‫جهان عاري ازهاري است‪.‬‬
‫• در جنوب شرقي آسيا‪ ،‬فيليپين‪ ،‬آفريقا‪ ،‬شبه قاره هند و‬
‫مناطق گرمسيري آمريكاي جنوبي از شيوع بيشتري‬
‫برخورداراست‬
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‫وضعيت هاري درايران‬
‫• تقريبا همه استانها كم و بيش با مشكل هاري‬
‫مواجه هستند‬
‫بيشترين موارد هاري در ‪:‬‬
‫• حاشيه درياي خزر‬
‫• شمال شرقي‬
‫• جنوب غربي‬
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‫گزارش ‪ 2‬مورد ناش ي ازپيوند قرنيه درايران‬
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‫گزارش ‪ 2‬مورد ناش ي ازپيوند قرنيه درايران‬
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‫تاثيرفصل‬
‫• در بعض ي از مناطق گرمسيري‪ ،‬در فصل پاييز و‬
‫زمستان به دنبال شيوع هاري سگسانان‪،‬‬
‫موارد هاري انساني هم افزايش مييابد‪.‬‬
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5 – Age,
Gender,
Occupation,
Social conditions
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‫تاثيرسن و جنس‬
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‫قريب دوسوم تا سه چهارم موارد هاري‪ ،‬در جنس‬
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‫مذكر و به طور كلي‪ ،‬بيشترين موارد بيماري‪ ،‬در‬
‫سنين كمتراز ‪ 20‬سالگي بروزمينمايد‪.‬‬
‫‪ %40‬هارگزيدگان را كودكان كمتراز‪ 15‬ساله‬
‫تشكيل ميدهند (‪)2014‬‬
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6 – Predisposing factors
& suitable conditions
• A bite with prominent salivary
contamination (Bare skin (
• Multiple bites
• Bites on the face
• Salivary contamination of broken skin
• Mucus contamination
• Aerosolization (Respiratory tract)
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7 – Susceptibility and Resistance
• All mammals are susceptible
• Humans are more resistant than several
animal species
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Susceptibility of various
animal to rabies
Very High
Wolves
Foxes
Coyotes
Kangaroo
rats
Cotton rats
Jackals
Voles
High
Hamsters
Skunks
Raccoons
Domestic
cats
Rabbits
Bats
Cattle
Moderate
Low
Dogs
Opossums
Primates
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‫‪8 – Secondary attack rate‬‬
‫با توجه به عدم گزارش مستند انتقال هاري ازطريق‬
‫تماس يا گازگرفتن انسان و يا وجود گزارشهاي بسيار‬
‫ناچيز‪ ،‬ميتوان چنين نتيجه گرفت كه ميزان حملت‬
‫ثانويه آن ازانسان به انسان درحد ِصفرتا بسيارپايين‪،‬‬
‫ميباشد‪.‬‬
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9 - Transmission
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Bite of the rabid animals
A fresh break in the skin
Intact mucous membrane
Person to person ?
Organ transplantation
Airborne spread from bats
Airborne spread in laboratory
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Period of communicability
• In dogs and cats for 3-7 days
before onset of clinical signs and
throughout the course of the
disease
• 14 days before onset, in Ethiopian
dogs
• In bats 12 days before evidence of
illness
• Skunks , 8 days before . . .
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Reservoir
• Caribbean: Mongoose ‫ميمون پوزه دراز‬
• Europe: Red fox
• Iran: Wolf
• Africa: Jackal
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Global distribution of mammalian rabies
reservoirs and vectors
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Animal bite in Iran
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Animal bite and human rabies in Iran
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Animal rabies in Iran
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Rabid wolves are associated with severe bites and human 45deaths
Raccoons are social animals Well adapted to living at high
population densities (urban/suburban) Prefer forested habitat
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A productive pathogenesis cycle of animal rabies: virus entry into peripheral nerves via a bite,
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movement to the central nervous system resulting in encephalitis, and transit to the salivary
glands, mediating infection of another host. Rupprecht CE et al, The Lancet Infectious Diseases Vol 2 June 2002
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Foxes maintain rabies from Arctic areas to temperate and tropical latitudes
Arctic fox
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The Jackal is an important candid reservoir of rabies in the old world
Hosts 6/7 lyssavirus genotypes
Widespread throughout North
America, Latin America
Infection rates in bats varies
(4% to > 15%)
Humans encounter bats that are
sick, incapacitated
Different bat species vary in
their human interaction
Primary reservoir for rabies in
All continents.
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Prevention
and
Control
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Prevention and Control
• Primary Prevention:
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Prevention of disease in “well” individuals
• Secondary Prevention:
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Identification and intervention in early
stages of disease
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Tertiary Prevention:
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Prevention of further deterioration,
reduction in complications
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Primary Prevention:
Pre-exposure prophylaxis:
• vaccination of people in high risk
groups:
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Veterinarians
Animal handlers
Certain lab workers
Travel to areas where canine rabies
is common
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Primary Prevention:
Pre-exposure prophylaxis:
• vaccination: intramuscular,
• 1ml (3 doses): at 0, 7, 21-28 days
• Antibodies usually persist for 2 yrs
• Repeat titers q6-24 months
depending on level of exposure
• Acceptable titer levels are 0.5 IU/ml
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Rabies vaccines
• Human Diploid Cell Vaccine
(HDCV)
• Purified vero cell vaccine
(PVRV)
• Purified chicken embryo cell
(PCEC)
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Post-exposure wound care
• Prevent virus in wound from reaching
neural tissue
• Prompt and thorough cleaning: flush
wound with soap and water
• Benzalkonium chloride not superior to
soap
• Update tetanus immunization
• Treat secondary bacterial infection
• Do not suture wound if possible
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Post-exposure Prophylaxis
• Exposure other than bite rarely
causes infection
• Prophylaxis to patients with
• open wound
• scratch
• mucous membrane
contaminated by :
• saliva or
• potentially infectious material from rabid
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animal
Post-exposure Prophylaxis
Human Exposure with Rabies
• Prophylaxis to people with sig. exposure to a
rabies pt. if
• scratch
• bite
• mucous membrane exposure to saliva or infectious tissue
• No prophylaxis if casual contact (touching) or
exposure to non-infectious material (urine,
stool)
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Post-exposure Prophylaxis
... ‫ پزشكان‬،‫اقدامات الزم براي مراقبين (پرستاران‬
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Standard universal precautions
Respiratory precautions
Pre-exposure prophylaxis
Check the antibody titer (~ 0.5 IU/mL)
Exposures to potentially contaminated secretions or
tissues should lead to standard PET
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Post-exposure immunoprophylaxis
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Passive and active
Start ASAP (As soon as possible)
RIG and rabies vaccine
Vaccine : one of the 3 types (5 doses),
same dose for all ages
• 1.0 ml IM at 0, 3, 7, 14, 28 d
• Intradermal regimens:used alternatively
• Avoid gluteal injection: less antibody
response than deltoid .
Red Book 2003
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Post-exposure immunoprophylaxis
• Human RIG is Given at the same time with
the vaccine (ASAP)
• Dose: 20 IU/kg
• As much as possible to infiltrate the wound
• Remainder is given IM (is not the first choice)
• RIG and vaccine are Give at different sites &
in different syringes
• Purified equine RIG : dose is 40 IU/kg, may
need desensitization
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2 - Secondary Prevention:
Identification
And
intervention
in early stages of
disease
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Rabies/Diagnosis
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Frequently missed
Lab tests are non diagnostic
Hyponatremia: inadequate intake, SIADH
hypernatremia,: rare
CSF analysis normal in 1/3 of patients in the 1st
wk of illness
• CSF: viral meningoencephalitis
• EEG and head CT may be normal early in
illness
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Rabies/Diagnosis
• MRI: abnormal, ill defined, increase
signal intensity on T-2 images
• Areas involved: brainstem,
hippocampi, hypothalami, deep &
subcortical white and grey matter
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Rabies/Diagnosis
Tissue studies
• Brain tissue: culture, histology for
Negri bodies
• Immunohistochemistry on tissue
• Brain tissue: Immunostain
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Rabies/Diagnosis
• Rabies specific antibodies in serum or CSF
(RFFIT)
• Serology positive in serum in 7 days of
symptoms
• Serology positive in CSF in 13 days of
symptoms
• Rabies vaccine does not cause positive CSF
antibodies
• Molecular studies, monoclonal antibodies in
epidemiologic studies
Hammond GW (Principles and Practice of Pediatric Infectious diseases)
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Section of rabid human brain processed by the DFA test, showing widespread viral
inclusions, staining apple-green in colour
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Rupprecht CE, The Lancet Infectious Diseases Vol 2 June 2002
A neuron from a formalin-fixed section of a brain from a patient with rabies,
showing reddish-brown viral inclusions in the cytoplasm. Processed by
immunohistochemistry.
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Rupprecht CE, The Lancet Infectious Diseases Vol 2 June 2002
Diagnosis of Rabies
Negri Body in neuron cell
(source: CDC)
Positive DFA test (Source: CDC
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2 - Secondary Prevention
Treatment of Rabies
• No specific treatment once
symptoms have begun
• Intensive care
• Almost all patients succumb to
disease in a few weeks
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Secondary Prevention
Treatment of Rabies
• The 3 patients in the 1970s
survived
• A child in 1994 which received
only rabies vaccine
• No effective drug
• No benefit of interfrons, Ribavirin
& Cytosine arabinoside
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3 - Tertiary Prevention:
• Surgical intervention
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Sources :
• Mandell, Douglas, Bennett; Principles and Practice of Infectious Diseases,
6th edition, 2015.
• Kasper, Braunwald, Fauci, Hauser, Longo, Jameson : Harrison's Principles
of Internal Medicine; 18th Edition, 2012
• Feigin, Cherry, Demmler, Kaplan : Textbook of Pediatric Infectious
Diseases, 6th edit., Saunders, 2008.
• David L. Heymann (edit.): Control of Communicable Diseases Manual, 19th
Edition, 2008,
• CDC Internet Site, 2011
• WHO, Fact Sheet N°99, September 2014
Tony J. and Leoni G. Causes, Effects, in Animals and Humans Tony J. and
Leoni G.
Lillian A. Orciari, Epidemiology of Rabies
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Sources :
• Rabies Management Guideline, A compendium of rabies control measures
and planning strategies compiled by the Maine Rabies Work Group – 2005,
pp. 1-107.
• WHO Expert Consultation on Rabies (2004 : Geneva, Switzerland) WHO
Expert Consultation on Rabies : first report.(WHO technical report series ;
931), World Health Organization 2005, PP. 1-121
• Arjun Srinivasan, Elizabeth C. Burton . . . Transmission of Rabies Virus
from an Organ Donor to Four Transplant Recipients, New England Journal
of Medicine, 2005; 352: 1103-11.
• Rodney E. Willoughby, Jr. . . . Survival after Treatment of Rabies with
Induction of Coma, New England Journal of Medicine, 2005;352:2508-14.
• Charles E. Rupprecht, Robert V. Gibbons, Prophylaxis Against Rabies,
New England Journal of Medicine, 2004;351:2626-35.
،‫ بيماريهاي مهم مشترك بين انسان و حيوان در ايران‬: ‫ در‬،‫ بيماري هاري‬،‫ سوسن‬،‫ ـ سيماني‬33•
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•
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