Global Health Update January 19, 2011 Ann Settgast, MD, DTM&H Center for International Health

For which of these patients would you recommend rabies PrEP (Pre-exposure Prophylaxis) and why? A. Adult male backpacking across India for 6 months B. Toddler child moving to Costa Rica for the year with her missionary parents C. Adult female working with MSF in Angola for 4 months D. Adult female working in Tanzania for 2 weeks on a filming project about HIV awareness E. Adult male visiting Mumbai for 5 days for business F. Adult female PhD candidate spending one month in Bangladesh to do diarrhea research G. Adult female bikeriding around the island of Bali for 3 weeks H. Adult male med/peds resident doing a two-month rotation in Bolivia

Why rabies discussion is important in travel medicine ~ 55,000 human rabies deaths per year world-wide ~ 55,000 human rabies deaths per year world-wide Likely under-reported, especially due to misdiagnosis of paralytic form Likely under-reported, especially due to misdiagnosis of paralytic form Only way to guarantee survival in an exposed unimmunized patient is to give post-exposure prophylaxis (PEP) Only way to guarantee survival in an exposed unimmunized patient is to give post-exposure prophylaxis (PEP) PEP= vaccine plus RIG PEP= vaccine plus RIG

Where in the world is rabies? Over 100 countries and all continents Over 100 countries and all continents Vast majority of deaths in Africa & Asia Vast majority of deaths in Africa & Asia 20,000 deaths in India 20,000 deaths in India China second to India in # of deaths China second to India in # of deaths 24,000 deaths in Africa 24,000 deaths in Africa 80% in rural areas 80% in rural areas

Bangladesh Highest per capita death rate from rabies - one in every 30,000 Highest per capita death rate from rabies - one in every 30,000 This would = 100 rabies deaths per year in the Twin Cities!! This would = 100 rabies deaths per year in the Twin Cities!!

Bali – rabies free Until…

Sept 2008, two adults died two months after being bitten, “… it would be a major concern if the dogs were infected with rabies, because no vaccine … is stored on the island.” (Jakarta Post) Sept 2008, two adults died two months after being bitten, “… it would be a major concern if the dogs were infected with rabies, because no vaccine … is stored on the island.” (Jakarta Post) Dec 2008, the Indonesian authorities reported a rabies outbreak in dogs on Bali Dec 2008, the Indonesian authorities reported a rabies outbreak in dogs on Bali Jan 2009, “Commendable efforts being made … to achieve control by culling and (dog) vaccination. Strangely, medical authorities seem reluctant to employ post-exposure vaccination to protect human population.” Jan 2009, “Commendable efforts being made … to achieve control by culling and (dog) vaccination. Strangely, medical authorities seem reluctant to employ post-exposure vaccination to protect human population.” Mar 2009, “Little precise information has been reported concerning the course of the outbreak and… consequent human fatalities. In particular, there is concern about the extent of the dog vaccination program and the availability of vaccine and immunoglobulin for PEP.” Mar 2009, “Little precise information has been reported concerning the course of the outbreak and… consequent human fatalities. In particular, there is concern about the extent of the dog vaccination program and the availability of vaccine and immunoglobulin for PEP.”

Sept 2009, 21 y/o female bitten by dog; rushed to regional hospital; wound was cleaned and sutured. 15 days later presented with inability to move legs, restlessness, and phobic to water. Given two rabies vaccines. Died. 9th fatality.Sept 2009, 21 y/o female bitten by dog; rushed to regional hospital; wound was cleaned and sutured. 15 days later presented with inability to move legs, restlessness, and phobic to water. Given two rabies vaccines. Died. 9th fatality. Oct 2009, Indonesia MOH reported 15 deaths - most cases near popular tourist destinations on the southern tip of BaliOct 2009, Indonesia MOH reported 15 deaths - most cases near popular tourist destinations on the southern tip of Bali April 2010, “…important for patients and families to seek medical advice as soon as any of the classic rabies symptoms are exhibited…They should get anti-rabies vaccines immediately," he said.April 2010, “…important for patients and families to seek medical advice as soon as any of the classic rabies symptoms are exhibited…They should get anti-rabies vaccines immediately," he said. September 2010, 93 deaths (165 people bitten by dogs daily)September 2010, 93 deaths (165 people bitten by dogs daily) As of last week, 118 deaths recordedAs of last week, 118 deaths recorded

How many do NOT die of rabies? Estimated that in the absence of PEP (post-exposure prophylaxis), 327,000 persons in Africa and Asia would die each year Estimated that in the absence of PEP (post-exposure prophylaxis), 327,000 persons in Africa and Asia would die each year Manufacturer data suggest that > 15 million people receive PEP annually (majority in India and China) Manufacturer data suggest that > 15 million people receive PEP annually (majority in India and China) “Rabies vaccines: WHO position paper”, No. 32, 2010

Rabies Immune Globulin (RIG) Produced by a limited # of companies in the developing world Produced by a limited # of companies in the developing world In the developing world, < 1% of those w/ serious exposures receive it! In the developing world, < 1% of those w/ serious exposures receive it! Human (HRIG) preferred (longer half-life) Human (HRIG) preferred (longer half-life) Newer Equine formulations (ERIG): potent, highly purified, safe, much less $$ Newer Equine formulations (ERIG): potent, highly purified, safe, much less $$ Small, but real risk of anaphylaxis and serum- sicknessSmall, but real risk of anaphylaxis and serum- sickness J Travel Med 2005; 12:s30-s40

Vaccine All cell culture vaccines induce prompt and high neutralizing Ab response All cell culture vaccines induce prompt and high neutralizing Ab response Intradermal regimens well-proven (assuming proper administration) and widely usedIntradermal regimens well-proven (assuming proper administration) and widely used Nerve tissue vaccines (still used in a few countries): less immunogenic +more severe reactions Nerve tissue vaccines (still used in a few countries): less immunogenic +more severe reactions “Rabies vaccines: WHO position paper”, No. 32, 2010

Not all travelers need PrEP (Pre-Exposure Prophylaxis) But all need education! But all need education! Rabies vaccine at Health Partners Travel Clinic is $329 + admin fee Rabies vaccine at Health Partners Travel Clinic is $329 + admin fee But…once correctly immunized w/ PrEP, no need for RIG But…once correctly immunized w/ PrEP, no need for RIG 76% of 300 surveyed German and Swiss GPs seeing patients (going to developing countries) for pre-travel advice did not discuss rabies with the traveler (J Trav Med 1999; 6: ) 76% of 300 surveyed German and Swiss GPs seeing patients (going to developing countries) for pre-travel advice did not discuss rabies with the traveler (J Trav Med 1999; 6: )

Factors to consider in pre-travel consultation… Probability of exposure: Probability of exposure: Incidence of rabies in the areaIncidence of rabies in the area Probability of contact with infected animalProbability of contact with infected animal*Children Ability to access local after-care (remoteness of travel and time to reach medical care) Ability to access local after-care (remoteness of travel and time to reach medical care) Competence of local after-care Competence of local after-care

Back to Bali One million tourists visited Bali Jan to June 2009 One million tourists visited Bali Jan to June 2009 PrEP for all would cost $750,000,000 (at U.S. rates) PrEP for all would cost $750,000,000 (at U.S. rates) If risk of being bitten is 1 in 6000 (based on study of tourists in Nepal), then total cost of giving PEP to only those who exposed would be 166 times $4000, which equals $664,000 If risk of being bitten is 1 in 6000 (based on study of tourists in Nepal), then total cost of giving PEP to only those who exposed would be 166 times $4000, which equals $664,000

However… Sometimes decision to give PEP is a no-brainer, but process can still be very stressful for patient and provider Sometimes decision to give PEP is a no-brainer, but process can still be very stressful for patient and provider Situation is much easier if PrEP has been given (especially when severity of exposure is less obvious). Situation is much easier if PrEP has been given (especially when severity of exposure is less obvious).

How do you know where RIG is available? Mumbai, India – H Mumbai, India – H Most other cities in India - E Most other cities in India - E Islamabad, Pakistan – H Islamabad, Pakistan – H Kathmandu, Nepal – H Kathmandu, Nepal – H Bangkok – H Bangkok – H 64% of 500 Thai Hospitals surveyed (J Trav Med 1998) 64% of 500 Thai Hospitals surveyed (J Trav Med 1998) Hong Kong Hong Kong Singapore Singapore HCMC and Hanoi, Viet Nam only at Int’l SOS clinic HCMC and Hanoi, Viet Nam only at Int’l SOS clinic Beijing, China – “controlled & limited” Beijing, China – “controlled & limited” Ulanbatter, Mongolia Ulanbatter, Mongolia Lagos, Nigeria – “occasionally E, but none at the moment” Lagos, Nigeria – “occasionally E, but none at the moment” Acra, Ghana Acra, Ghana Durban, South Africa Durban, South Africa Large cities in Brazil – B Large cities in Brazil – B Lima, Peru – E Lima, Peru – E Medellin, Columbia – E Medellin, Columbia – E Costa Rica Costa Rica Cuzco, Peru Cuzco, Peru Bali Bali Source: informal survey sent to 40 clinics (ISTM) in 20 developing countries ~ 75% response rate You don’t!

Counseling a traveler Avoid stray or unknown domestic animals Avoid stray or unknown domestic animals If bitten, immediately flush wound with soap/water If bitten, immediately flush wound with soap/water Seek urgent medical attention, preferably in specialized center Seek urgent medical attention, preferably in specialized center Request cell culture vaccine only Request cell culture vaccine only Insist on RIG Insist on RIG

Now, for which of these patients would you recommend rabies PrEP (Pre- exposure Prophylaxis) and why? A. Toddler child moving to Costa Rica for the year with her missionary parents A. Toddler child moving to Costa Rica for the year with her missionary parents B. Adult female bikeriding around Bali for 3 weeks B. Adult female bikeriding around Bali for 3 weeks C. Adult female PhD candidate spending one-month in Bangladesh to do diarrhea research C. Adult female PhD candidate spending one-month in Bangladesh to do diarrhea research D. Adult male backpacking across India for 6 months D. Adult male backpacking across India for 6 months E. Adult female working with MSF in Angola for 4 months E. Adult female working with MSF in Angola for 4 months F. Adult female working in Tanzania for 2 weeks on a filming project about HIV awareness F. Adult female working in Tanzania for 2 weeks on a filming project about HIV awareness G. Adult male visiting Mumbai, India for 5 days for business G. Adult male visiting Mumbai, India for 5 days for business H. Adult male med/peds resident doing a two-month rotation in Bolivia H. Adult male med/peds resident doing a two-month rotation in Bolivia