Global Health UpdateGlobal Health Update

January 19, 2011January 19, 2011

Ann Settgast, MD, DTM&HAnn Settgast, MD, DTM&HCenter for International HealthCenter for International Health

For which of these patients would you For which of these patients would you recommend rabies PrEP (Pre-exposure recommend rabies PrEP (Pre-exposure

Prophylaxis) and why?Prophylaxis) and why? A. Adult male backpacking across India for 6 monthsA. Adult male backpacking across India for 6 monthsB. Toddler child moving to Costa Rica for the year with her B. Toddler child moving to Costa Rica for the year with her

missionary parentsmissionary parentsC. Adult female working with MSF in Angola for 4 monthsC. Adult female working with MSF in Angola for 4 monthsD. Adult female working in Tanzania for 2 weeks on a filming D. Adult female working in Tanzania for 2 weeks on a filming

project about HIV awarenessproject about HIV awarenessE. Adult male visiting Mumbai for 5 days for businessE. Adult male visiting Mumbai for 5 days for businessF. Adult female PhD candidate spending one month in F. Adult female PhD candidate spending one month in

Bangladesh to do diarrhea researchBangladesh to do diarrhea researchG. Adult female bikeriding around the island of Bali for 3 weeksG. Adult female bikeriding around the island of Bali for 3 weeksH. Adult male med/peds resident doing a two-month rotation in H. Adult male med/peds resident doing a two-month rotation in

BoliviaBolivia

Why rabies discussion is important Why rabies discussion is important in travel medicinein travel medicine

~ 55,000 human rabies deaths per ~ 55,000 human rabies deaths per year world-wideyear world-wide

Likely under-reported, especially due Likely under-reported, especially due to misdiagnosis of paralytic formto misdiagnosis of paralytic form

Only way to Only way to guarantee guarantee survival in an survival in an exposed exposed unimmunizedunimmunized patient is to patient is to give post-exposure prophylaxis (PEP)give post-exposure prophylaxis (PEP)

PEP= vaccine PEP= vaccine plusplus RIG RIG

Where in the world Where in the world is rabies?is rabies?

Over 100 countries and all continentsOver 100 countries and all continents Vast majority of deaths in Africa & AsiaVast majority of deaths in Africa & Asia 20,000 deaths in India20,000 deaths in India China second to India in # of deathsChina second to India in # of deaths 24,000 deaths in Africa24,000 deaths in Africa 80% in rural areas80% in rural areas

BangladeshBangladesh Highest per capita Highest per capita

death rate from rabies death rate from rabies - one in every 30,000- one in every 30,000

This would = 100 This would = 100 rabies deaths per year rabies deaths per year in the Twin Cities!! in the Twin Cities!!

Bali – rabies freeBali – rabies freeUntil…

Sept 2008, two adults died two Sept 2008, two adults died two months after being bitten, “… it months after being bitten, “… it would be a major concern if the would be a major concern if the dogs were infected with rabies, dogs were infected with rabies, because no vaccine … is stored on because no vaccine … is stored on the island.” (Jakarta Post) the island.” (Jakarta Post)

Dec 2008, the Indonesian authorities Dec 2008, the Indonesian authorities reported a rabies outbreak in dogs reported a rabies outbreak in dogs on Balion Bali

Jan 2009, “Commendable efforts Jan 2009, “Commendable efforts being made … to achieve control by being made … to achieve control by culling and (dog) vaccination. culling and (dog) vaccination. Strangely, medical authorities seem Strangely, medical authorities seem reluctant to employ post-exposure reluctant to employ post-exposure vaccination to protect human vaccination to protect human population.”population.”

Mar 2009, “Little precise information Mar 2009, “Little precise information has been reported concerning the has been reported concerning the course of the outbreak and… course of the outbreak and… consequent human fatalities. In consequent human fatalities. In particular, there is concern about particular, there is concern about the extent of the dog vaccination the extent of the dog vaccination program and the availability of program and the availability of vaccine and immunoglobulin for vaccine and immunoglobulin for PEP.”PEP.”

•Sept 2009, 21 y/o female bitten by dog; rushed to regional hospital; wound 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 was cleaned and sutured. 15 days later presented with inability to move legs, restlessness, and phobic to water. Given two rabies vaccines. Died. legs, restlessness, and phobic to water. Given two rabies vaccines. Died. 9th fatality. 9th fatality. •Oct 2009, Indonesia MOH reported 15 deaths - most cases near popular Oct 2009, Indonesia MOH reported 15 deaths - most cases near popular tourist destinations on the southern tip of Balitourist destinations on the southern tip of Bali•April 2010, “…important for patients and families to seek medical advice April 2010, “…important for patients and families to seek medical advice as soon as any of the classic rabies symptoms are exhibited…They should as soon as any of the classic rabies symptoms are exhibited…They should get anti-rabies vaccines immediately," he said. 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?How many do NOT die of rabies?

Estimated that in the absence of PEP Estimated that in the absence of PEP (post-exposure prophylaxis), 327,000 (post-exposure prophylaxis), 327,000 persons in Africa and Asia would die persons in Africa and Asia would die each yeareach year

Manufacturer data suggest that > 15 Manufacturer data suggest that > 15 million people receive PEP annually million people receive PEP annually (majority in India and China)(majority in India and China)

“Rabies vaccines: WHO position paper”, No. 32, 2010

Rabies Immune Globulin (RIG)Rabies Immune Globulin (RIG) Produced by a limited # of companies in the Produced by a limited # of companies in the

developing worlddeveloping world In the developing world, < 1% of those w/ In the developing world, < 1% of those w/

serious exposures receive it!serious exposures receive it! Human (HRIG) preferred (longer half-life)Human (HRIG) preferred (longer half-life) Newer Equine formulations (ERIG): potent, Newer Equine formulations (ERIG): potent,

highly purified, safe, much less $$highly purified, safe, much less $$• Small, but real risk of anaphylaxis and serum-Small, but real risk of anaphylaxis and serum-

sicknesssickness

J Travel Med 2005; 12:s30-s40

VaccineVaccine All cell culture vaccines induce prompt All cell culture vaccines induce prompt

and high neutralizing Ab response and high neutralizing Ab response • Intradermal regimens well-proven Intradermal regimens well-proven

(assuming proper administration) and (assuming proper administration) and widely usedwidely used

Nerve tissue vaccines (still used in a Nerve tissue vaccines (still used in a few countries): less immunogenic few countries): less immunogenic +more severe reactions +more severe reactions

“Rabies vaccines: WHO position paper”, No. 32, 2010

Not all travelers need PrEPNot all travelers need PrEP(Pre-Exposure Prophylaxis)(Pre-Exposure Prophylaxis)

But all need education!But all need education! Rabies vaccine at Health Partners Travel Rabies vaccine at Health Partners Travel

Clinic is $329 + admin fee Clinic is $329 + admin fee But…once correctly immunized w/ PrEP, no But…once correctly immunized w/ PrEP, no

need for RIG need for RIG 76% of 300 surveyed German and Swiss 76% of 300 surveyed German and Swiss

GPs seeing patients (going to developing GPs seeing patients (going to developing countries) for pre-travel advice did not countries) for pre-travel advice did not discuss rabies with the traveler (discuss rabies with the traveler (J Trav MedJ Trav Med 1999; 6:163-167)1999; 6:163-167)

Factors to consider in pre-travel Factors to consider in pre-travel consultation…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*Children Ability to access local after-care Ability to access local after-care

(remoteness of travel and time to reach (remoteness of travel and time to reach medical care) medical care)

Competence of local after-careCompetence of local after-care

Back to BaliBack to Bali

One million tourists visited Bali Jan to One million tourists visited Bali Jan to June 2009June 2009

PrEP for all would cost PrEP for all would cost $750,000,000$750,000,000 (at U.S. rates)(at U.S. rates)

If risk of being bitten is 1 in 6000 If risk of being bitten is 1 in 6000 (based on study of tourists in Nepal), (based on study of tourists in Nepal), then total cost of giving PEP to only then total cost of giving PEP to only those who exposed would be 166 those who exposed would be 166 times $4000, which equals times $4000, which equals $664,000$664,000

However…However…

Sometimes decision to give PEP is a Sometimes decision to give PEP is a no-brainer, but process can still be no-brainer, but process can still be very stressful for patient and very stressful for patient and providerprovider

Situation is much easier if PrEP has Situation is much easier if PrEP has been given (especially when severity been given (especially when severity of exposure is less obvious).of exposure is less obvious).

How do you know where RIG is available?How do you know where RIG is available? Mumbai, India – HMumbai, India – H Most other cities in India - EMost other cities in India - E Islamabad, Pakistan – HIslamabad, Pakistan – H Kathmandu, Nepal – HKathmandu, Nepal – H Bangkok – HBangkok – H 64% of 500 Thai Hospitals surveyed (64% of 500 Thai Hospitals surveyed (J Trav J Trav

MedMed 1998) 1998) Hong KongHong Kong SingaporeSingapore HCMC and Hanoi, Viet Nam only at Int’l HCMC and Hanoi, Viet Nam only at Int’l

SOS clinicSOS clinic Beijing, China – “controlled & limited”Beijing, China – “controlled & limited” Ulanbatter, MongoliaUlanbatter, Mongolia Lagos, Nigeria – “occasionally E, but none Lagos, Nigeria – “occasionally E, but none

at the moment”at the moment” Acra, GhanaAcra, Ghana Durban, South AfricaDurban, South Africa Large cities in Brazil – BLarge cities in Brazil – B Lima, Peru – ELima, Peru – E Medellin, Columbia – EMedellin, Columbia – E

Costa RicaCosta Rica Cuzco, PeruCuzco, Peru BaliBali

Source: informal email survey sent to 40 clinics (ISTM) in 20 developing countries ~ 75% response rate

You don’t!

Counseling a travelerCounseling a traveler

Avoid stray or unknown domestic Avoid stray or unknown domestic animalsanimals

If bitten, immediately flush wound If bitten, immediately flush wound with soap/water with soap/water

Seek urgent medical attention, Seek urgent medical attention, preferably in specialized centerpreferably in specialized center

Request cell culture vaccine onlyRequest cell culture vaccine only Insist on RIG Insist on RIG

Now,Now, for which of these patients would for which of these patients would you recommend rabies PrEP (Pre-you recommend rabies PrEP (Pre-exposure Prophylaxis) and why?exposure Prophylaxis) and why?

A. Toddler child moving to Costa Rica for the year with her A. Toddler child moving to Costa Rica for the year with her missionary parentsmissionary parents

B. Adult female bikeriding around Bali for 3 weeksB. Adult female bikeriding around Bali for 3 weeks C. Adult female PhD candidate spending one-month in C. Adult female PhD candidate spending one-month in

Bangladesh to do diarrhea researchBangladesh to do diarrhea research D. Adult male backpacking across India for 6 monthsD. Adult male backpacking across India for 6 months E. Adult female working with MSF in Angola for 4 monthsE. Adult female working with MSF in Angola for 4 months

F. Adult female working in Tanzania for 2 weeks on a F. Adult female working in Tanzania for 2 weeks on a filming project about HIV awarenessfilming project about HIV awareness

G. Adult male visiting Mumbai, India for 5 days for businessG. Adult male visiting Mumbai, India for 5 days for business H. Adult male med/peds resident doing a two-month H. Adult male med/peds resident doing a two-month

rotation in Boliviarotation in Bolivia