who setting the scene: the global burden of rabies and … · human rabies in india in 2005 knobel...
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Scene setting:Epidemiological and
geographical distribution of rabies and envenomings, and
the need for more good quality animal derived sera
Copyright D. A. WarrellUniversity of Oxford UK
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Rabies, snake bite and scorpion sting: what do they have in common?
Essential treatment involves the use of serum*produced in animals immunised with rabies vaccine or venom
*hyperimmune serum, antiserum, antivenom, antitoxin
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Clinical applications of animal-derived hyperimmune sera
• Infections: rabies, tetanus, diphtheria, botulism, gas gangrene
• Poisonings: drugs (digoxin), colchicine, plants• Envenomings: snakes, lizards, scorpions, spiders,
bees, caterpillars, fish, jellyfish, ticks• Emerging pathogens: avian influenza, new
hemorragic fever viruses• Bio-terrorism agents: diagnosis and antidote• Immuno-diagnosis: of all the above
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Animal-derived hyperimmune sera
• Raised in horse or sheep
• Refined immunoglobulin
• Liquid preparation or freeze-dried to prolong shelf life in tropical climates
Copyright D. A. Warrell
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RabiesCopyright D.A.Warrell
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Global distribution of classic rabies and European and Australian bat lyssaviruses
Copyright D.A. Warrell
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Human rabies in India in 2005
Knobel DL et al. Bull WHO 2005;83:360-8
•16 million bites•18,500-19,700 deaths•4 million post-exposure prophylaxis courses
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• 2,600 deaths (30% more than 2005)• ~8 million post-exposure prophylaxis courses
Human rabies in China in 2006
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Annual deaths from human rabies
24,000
32,000
36
9<40
Global annual total rabies deaths ~56,000
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Rabies 100% untreatable 100%
preventable with modern post-
exposure prophylaxis
• Wound cleaning• Passive immunisation
(rabies immune globulin - RIG)
• Active Immunisation with rabies vaccine
URGENT !
Copyright D.A. Warrell
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Rabies immunoglobulin (RIG): efficacy• Proved effective in study of 29 Iranian
villagers attacked by rabid wolf in 1954• Neutralises virus inoculated into wound
immediately: before it invades nervous system before antibody response to vaccination
• Recommended by all national/international authorities (WHO, CDC, HPA etc) for all category 3 exposures* (~ 65% of all post-exposure courses)
*transdermal bite(s)/scratch(es) or contamination of mucosae with saliva
• Unaffordable and unavailable in most developing countries
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Current use of rabies immune globulin (% of post-exposure courses)
• Africa: 1%• Asia: 6% (Philippines 8%)• Americas: ?
• Overall in developing countries: <1%
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Annual Global need for rabies immune globulin (RIG) (post-exposure treatments) if international
guidelines were to be fully implemented• Africa: 600,000 • Americas: 350,000 • Eastern Mediterranean: 200,000• West Pacific (including China): 9 millions• SE Asia (including India): 3.2 millions
Total 13.35 millions• Annual global requirement:
16 million vials** Assuming that 60% of PET courses require
RIG, average dose 2 vials/patient
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The horror of snake
bite!Spitting cobra bite Nigeria
Copyright D.A. Warrell
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Long term complications of
snake biteCopyright D.A.Warrell
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Snake bite: the global burden of human suffering
• How many bites?• How many fatalities?• How many permanent
sequelae?
Copyright, D.A. Warrell
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Snake bite: annual global mortality
Swaroop & Grabb 1954 (Bull World Health Organ 1954;10:35–76)
• 500,000 bites• 30,000-40,000 deathsChippaux 1998
(Bull World Health Organ. 1998;76(5):515-24) • 5 million bites• 125,000 deaths• 100,000 severe sequelae
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Estimated annual burden of snake bite
bites envenomings deaths
Americas 500,000 200,000 (40%) 4,000 (2%)
Africa 1 million 400,000 (40%) 20,000 (5%)
Asia 3 millions 1.2 millions (40%)
60,000 (5%) (India 50,000)
Oceania 5,000 2,500 (50%) 250 (10%)
Total >4.5 millions >1.8 millions >80,000
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Centruroideselegans
C.noxius
C. limpidus
• México: formerly 300,000 stings, 2,000 deaths/year; now 250,000 stings, <50 deaths/year
• Iran Khuzestan province: 25,000 stings treated/yr fourth major cause of death
• Algeria: 150 deaths in 1998, 74 in 2005, 62 in 2006 (9/12)
• Tunisia: ~ 40,000 stings, ~1,000 hospital admissions, 100 deaths/yr Cop
Scorpion stings: annual incidence
yright D.A. Warrell
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Scorpion sting in Latin America (Tityus serrulatus) Copyright D.A.Warrell
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Antivenoms for snake bites and scorpion stings
• Antivenom is the only specific antidote
• Effective in saving lives and preventing persistent complications
• Crisis in supply for Africa
Copyright D.A.Warrell
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Antivenom safetyEarly anaphylactoid reactions
• Incidence as high as 84% but can be reduced to <3% by improving production methods
• Readily treatable (adrenaline)
• Very low mortality
• Benefit>>risk
Copyright D.A.Warrell
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1.8 million snake bite envenomings/year:
therapeutic implications
• Assume each case needs a treatment course of 1-20 (average 5) vials of antivenom
• Annual global requirement = 9 million vials
• + guidelines and training for appropriate use
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Scorpion stings: therapeutic implications
• Mexico alone records ~250,000 stings and produces 500,000 vials of scorpion antivenom/year
• Globally perhaps >1 million cases needing antivenom treatment/year
• Annual global requirement for scorpion antivenom, assuming average dose of 1 vial /patient = 1 million vials
• + guidelines and training for appropriate use
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Global requirements for animal derived antisera: summary
• Rabies: annual global requirement: 16 million vials of RIG
• Snake bite and scorpion stings annual global requirement: 10 million vials of antivenom
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Rabies, snake bites and scorpion stings kill >200,000 people each year
• Less than one tenth of the deaths attributed to each of the “multi-million killers” TB, HIV, malaria, ARI
• But the the total burden of human suffering attributable to rabies, snake bites and scorpion stings is not adequately reflected merely by the number of fatalities
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Contributing to the total burden of human suffering
• Rabid mammal (dog) bites, snake bites and scorpion stings are terrifying and painful
• In the case of suspected rabies exposure, the victim is condemned to a protracted period of anxiety (“Will I develop rabies?”)
• In the case of a snake bite, the victim may be permanently maimed
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Conclusions
• Hyperimmune sera are essential drugsfor prevention of rabies and treatment of venomous bites and stings (and some other conditions)
• Quantity and quality of global production can be improved by a new WHO initiative