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Prof Robert Booy

NCIRS, University of Sydney

HealthEd Melbourne, October, 2015

There were about 9 million short-term departures from Australia in the 12month period 2013 -2014

Most frequently cited reason for short-term resident journeys from Australia: holidays (60%); visiting friends/relatives (VFR) (23%)

More than half of departures were to Asia, Africa, the Middle East, S & Central America, which places travellers at-risk for multiple VPDs

Many Australians do not seek pre-travel medical advice and may be unaware that they may be at risk and need to protect themselves

Some travellers are at a higher risk of VPDs

Those attending mass gatherings

religious/sporting events (e.g. Hajj /World Cup)

If aged over30 years would not have been vaccinated against hepatitis B through the NIP

Australians born during or since 1966 who have not received 2 doses of MMR vaccine

Older travellers (50+ years): under-vaccinated

Visiting Friends and Relatives (VFR): Migrant families/individuals travelling to country of origin

Routine

Childhood and adult immunisations

Required

According to risk of infection

Recommended

Specific requirements for crossing borders

Refer to the Immunisation Handbook and/or the CDC2 for country-specific recommendations Need to base decision on a number of factors

Can be thought of as: this traveller, this trip, this time

This Traveller

age, pregnancy (or planning), current meds, medical issues e.g. immunocompromise, immunisation history, allergies

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Intended itinerary, departure date

(incl. time period available for immunisations), specific localities and routes,

rural versus urban, duration of trip

likely access to healthcare, probability of deviation from itinerary, intended activities

required immunisations for entry/exit to specific countries

Any seasonal variations that need consideration?

Any outbreak warnings or travel warnings that need to be considered?

What future trips are they planning?

(e.g. likelihood to visit other at-risk areas later?)

Australian-specific information: routine immunisations and travel health

Australian Immunisation Handbook (updated 2014)

Centers for Disease Control and Prevention (CDC) “Yellow Book”: CDC Health Information for International Travel 2014

Destination-specific advice: wwwnc.cdc.gov/travel/destinations/list

World Health Organization (WHO) –International travel and health 2012 www.who.int/ith/en/ –International health regulations. www.who.int/ihr/en/

A serious, potentially life-threatening liver infection caused by the hepatitis B virus

Hepatitis B is found in blood & body fluids of infected people 30-50% of adults infected with hepatitis B get acute symptomsfever, jaundice, malaise, anorexia, nausea, vomiting, abdo pain Some people remain chronically infected ie carriers of the virus (~240 million people worldwide)

Chronic hep B infection is associated with premature mortality: cirrhosis or hepatocellular carcinoma in 25% cases

About 800,000 die every year

Immunisation is recommended for travellers to regions of intermediate or high endemicity, either long-term or for frequent short term trippers(most of the world!)

or who are likely to undertake activities that increase their risks of exposure to HBV

Half of Australian adults travelling to South East & East Asia reported in a 2004 telephone survey that they were not vaccinated, or were unsure of their vaccination status, for Hep B despite participating in at least one activity with risk of hepatitis B exposure on their last trip

Adapted from Yung A et al, 2011. *2003-04 Data (Zwar 2003)

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H-B-Vax® II 3 doses: 0, 1 & 6 months Engerix®-B ≥3 doses: 0, 1 & 6 months

Accelerated schedule:

where more rapid protection is required4 doses: 0, 1, 2 months or 0, 7 and 21 days

Plus a booster dose at 12 months is recommended to ensure adequate protection

3 doses: 0, 1 and 6 months

Accelerated schedule,

where more rapid protection is required:

4 doses: 0, 7 and 21 days

A booster dose at 12 months is recommended to ensure adequate protection

Mainly transmitted by the faecal-oral route, consuming food or drinks contaminated with the virus due to poor sanitary or hygiene practices 70% of infected adults are symptomatic, and suffer from systemic (fever, malaise, weakness and anorexia) and gastrointestinal (nausea and vomiting) symptoms

Rarely acute liver failure and deathCase-fatality rate increases with age, and is also high in people with other liver disease (i.e. chronic hepatitis B/C) Most patients feel better and their liver recovers within a

month, though relapse occurs in 10% of cases Does not cause chronic liver disease or chronic infection – Immunity after infection is life-long

Immunisation is recommended for travellers to (≥1 year of age), and expatriates living in, mod. to highly endemic areas for hepatitis Asia, Africa, Central & South America

Monovalent hepatitis A vaccines

Avaxim® Age≥2 yrs 2 doses: 0 & 6-36 months Havrix® Age ≥16 2 doses: 0 & 6-12 months Vaqta® Age ≥18 2 doses: 0 & 6-18 months

Vivaxim® ≥16yrs Single dose

For long-term protection, 2nd dose of hep A vaccine should be given 6-36 months later

Salmonella enterica subspecies enterica serovar Typhi(S. Typhi) Symptoms: high fever, headache, feeling unwell anorexia

Poor sanitation, poor food hygiene and untreated drinking water all contribute to endemic disease, with moderate to high incidence and considerable mortality

Worldwide: 22 million cases of typhoid fever/year

Australia: <150 cases of typhoid fever reported/year

-mostly in travellers going where typhoid is endemic..

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Recommended for adults travelling to endemic regions, where food hygiene may be suboptimal and drinking water may not be adequately treated

Recommended for adults travelling to endemic regions to visit friends and relatives

Travellers should be advised about personal hygiene, food safety and drinking boiled

or bottled water only. Raw (or undercooked) shellfish, salads, cold meats, untreated water and ice (in drinks) are all potentially ‘high-risk’, as are short (day) trips away from higher quality accom’n

Monovalent typhoid vaccines (purified Vi capsular polysaccharide vaccine)

Typherix® ≥2yrs Single dose Typhim Vi™ ≥2yrs Single dose

Monovalent typhoid vaccine (oral live attenuated) Vivotif® Oral ≥6yrs

3 doses: one capsule on days 1, 3 & 5taken 1 hr before food

A 4th dose (day 7) can also be given

Vivaxim® ≥16yrs Single doseFor long-term protection, 2nd dose of hep A vaccine should be given 6-36 months later

Typhoid Vaccine should be administered at least 14 days prior to potential exposure to S. typhiOn-going risk?: revaccinate after 3 yrs in general

but see Handbook for recommendations, as differs depending on which vaccine used initially

The Australian Immunisation Handbook recommends travellers (aged ≥9 months) who intend visiting countries where epidemics of group A, W135 or Y meningococcal disease are frequent be vaccinated with a quadrivalent men conjugate or polysaccharide vaccine (4vMenCV or 4vMenPV)

CDC recommends immunisation for travellers to regions to hyperendemic or endemic countries, especially if there is prolonged contact with the local population

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Quadrivalent meningococcal conjugate vaccines (4vMenCV) Nimenrix® 1 – 55 years Menactra® 2 – 55 years Menveo® ≥11 years

Quadrivalent meningococcal polysaccharide vaccines (4vMenPV)

Mencevax® ACWY >2 years Menomune® >2 years

Where not otherwise contraindicated, a single dose of 4vMenCV should be administered in preference to 4vMenPV

NHMRC recommend booster vaccinations every 5 years if the risk of meningococcal exposure is ongoing in individuals who are travelling to endemic or hyper-endemic regions or individuals who have other risks for meningococcal disease

28Source: McIntosh D. Presented at: 2013 Vaccine Preventable Diseases Conference; April 2013; Dublin, Ireland. Available at:

www.immunisation.ie/en/Conferences/2013VPDConference/PDFFile_17228_en.pdf (accessed Mar 2014)

Today: Happy but

happier if she had

been vaccinated

Will the vaccine

be recommended

for routine use?

New Men B vaccine

licensed in Australia

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Poliomyelitis (polio) is a viral infection that affects the central nervous system

Transmitted from person to person, or via the consumption of contaminated food or drinks due to poor sanitation or hygiene

Symptoms include headache, general aches and pains and stiffness of the neck and back. The most severe complication is paralysis

Primary immunization against polio:

The Australian Immunisation Handbook recommends that no adult should remain unvaccinated against poliomyelitis

The handbook recommends booster vaccination every 10 years for those at a continuing risk of infection, such as travellers to areas where polio is epidemic or endemic

Combination vaccines that contain IPV (dTpa-IPV)

Adacel® Polio

Boostrix®-IPV

Virus transmitted via the bite of an infected mosquito Most infections are asymptomatic

Symptoms include headache, fever, convulsions, focal neurological signs and depressed level of consciousness. Less commonly, may present as an acute flaccid paralysis High case-fatality rate and high prevalence of neurological sequelae (up to 50%) in those who survive the acute illness

Infection usually occurs in rural areas where there is prolific breeding of the vectors (e.g. in flooded rice fields)

Immunisation recommended for travellers (≥1 yr of age) spending ≥1 month in rural areas of high-risk countries in Asia and Papua New Guinea

JE Can occur after shorter periods of travel, so consider immunisation particularly if the travel is during the wet season, or anticipated to be repeated, and/or there is considerable outdoor activity, and/or the accommodation is not mosquito-proof –

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JE immunisation is also recommended for all other travellers spending ≥1 year in Asia except Singapore

even if much of the stay is in urban areas

All travellers to Asia (tropics in general) must be fully aware of the need to use personal protective measures to avoid mosquito bites

(Zika in the Pacific)

Live attenuated JE virus Imojev® ≥1 yrSingle dose SC injection into deltoid

Inactivated JE virus JESPECT® ≥18 yrs2 doses: days 0 and 28, IM injection deltoid

Imojev should be administered at least 14 days prior to potential JE virus exposure

The 2-dose schedule for JESPECT should be completed at least one week prior to exposure

An acute bacterial infection generally characterised by sudden onset painless, profuse, watery diarrhoea

Transmitted via food and water contaminated with Vibrio cholerae (i.e. from human excreta)

Substantial health burden in developing countries and considered to be endemic in Africa, Asia, South & Central America

Routine immunisation not recommended: the risk to travellers is very low, despite

endemicity in some countries – careful and sensible selection of food and water

is more important

Immunisation should be considered for travellers at increased risk of acquiring diarrhoeal disease at increased risk of severe or complicated

diarrhoeal disease with considerable risk of exposure to, or

acquiring, cholera, such as humanitarian disaster workers deployed to regions with e endemic or epidemic cholera

Dukoral® ≥2years

2 doses: 0 and 1-6 weeks

If 2nd dose not administered within 6 weeks, restart

Booster: single dose up to 2 years after primary course completion

If longer, repeat primary immunisation

What % of mammals?

What diseases?

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The fearless folly of youth Almost invariably fatal if not treated

Order: ChiropteraSuborder: Megachiroptera ("megabats")Family: Pteropodidae (flying foxes, Old World fruit bats)Transmits Hendra, Lyssa

Rabies

Lyssavirus: RNA virus

11 Lyssavirus species ◦ Classic Rabies virus (RABV) : genotype 1

◦ Australian bat Lyssavirus (ABLV): genotype 7

RABV causes most human rabies globally ◦ transmitted predominantly by dogs (Asia / Africa)

◦ racoons / skunks / foxes / coyotes / beavers (USA / Europe)

◦ bat-variant sub-lineages

◦ best control: mass vaccination dogs / managing dogs

Bali aims to be rid of Rabies by 2020

August 1996: bitten by macro-bat◦ rabies November 1998

October 1996: bitten by yellow sheathed micro-bat ◦ rabies November 1996

Clinical:◦ Early: non-specific: fever, headache, malaise

◦ As progresses: insomnia, anxiety, confusion, paralysis, excitation, hallucinations, agitation, hypersalivation, difficulty swallowing, hydrophobia

◦ Death within days of CNS symptoms

Animals: ◦ more aggressive or more tame / lose fear of people

◦ nocturnal bats may be out during the day, found on ground / unable to fly

◦ dogs: stagger, tremble, seem weak Allworth, A et al. A human case of encephalitis due to a Lyssavirus recently identified in fruit bats. CDI, 20, 504. 1996

Hanna JN et al. Australian bat lyssavirus infection: a second human case with a long incubation period. MJA 172, 597-599. 2000

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1st cases reported in Indonesia in 1884 – present in 24 of 33 provinces◦ Bali from 2008 - Very slow local action: >130 deaths by 2011 (no PEP)

◦ Improved dog vaccination / control & PEP >130,000: has deaths◦ Australia provided DFA test in Denpasar

Macaque bites more prominent than dog bites in Bali◦ No evidence as yet that they transmit rabies

Visitors strongly advised: avoid direct contact with dogs, cats, monkeys – avoid cute animals

RIG shortage in developing countries◦ Some still don’t receive RIG in Bali / too late for RIG on return

Not enough travellers receive pre-travel vaccination◦ Expensive

P. Gautret, P. L. Lim, M. Shaw, K. Leder. Rabies post-exposure prophylaxis in travellers returning from Bali, Indonesia, November 2008 to March 2010. Clinical Microbiology and Infection Volume 17, Issue 3, pages 445–447, March 2011

P. Gautret, P. L. Lim, M. Shaw, K. Leder Rabies post-exposure prophylaxis in travellers returning from Bali, Indonesia, November 2008 to March 2010. Clinical Microbiology and Infection Volume 17, Issue 3, pages 445–447, March 2011

http://smartraveller.gov.au/zw-cgi/view/Advice/Indonesia

Mosquitos trapped in amber

Origin: Gorillas Liu et al Nature 2010 Human P Falciparum forms monophyletic lineage within gorilla

parasite radiation

630,000 deaths/year mainly children, 90% in Africa

200 million people infected by P falciparum

Increasing drug and insecticide resistance

Complicated lifecycle, Ags expressed at different stages

Malaria genome sequenced – 5300 gene products( many potential targets)

Vaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001)

At low transmission (PrP₂₋₁₀ 10%) vaccine efficacy was 60% (95% CI 54 to 67)

At moderate transmission (PrP₂₋₁₀ 20%) it was 41%

At high transmission (PrP₂₋₁₀ 70%) the efficacy was 4%

Vaccine efficacy against clinical disease was of limited duration and was not detectable after 3 years

4th yr efficacy poor, 2013 NEJM article confirms.. But for every 100 children, 65 cases of malaria were averted!

Glass half full OR half empty?

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Modified intention-to-treat analyses

Followed for a median of 48 months

RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in infants & children when given with or without a booster dose (VEs 18%-32%)

Efficacy was enhanced by a booster dose

Meningitis was reported as a SAE in 22 children: 11 in the R3R group, ten in the R3C group, and one in t the C3C group

Stamaril® 1 ≥9 months* Single dose

A single dose of vaccine is sufficient to confer life-long immunity” – WHO

Avoid mosquitoes

Mosquito repellents, coils and sprays

Mosquito nets

Wear long sleeves and pants

300 million lives saved in 20th Century due to smallpox eradication

The ring vaccination strategy was crucial to success

The word “vaccination,” coined by Jenner in 1796, is derived from

the Latin root vaccinus, meaning of, or from, the cow

Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results Guinea ring vaccination cluster-randomised trial Lancet 2015 Aug 29

A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV)Open-label, cluster-randomised ring vaccination trial Suspected cases of Ebola virus disease in Basse-Guinéewere independently ascertained by Ebola response teams as part of national surveillance - Clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to vaccination immediately or delayed (21 days later) with rVSV-ZEBOV, randomisation, t stratified by urban v rural & size of rings

Between April & July 2015, 90 clusters were included 48 clusters (4123 people) were randomly assigned to

immediate vaccination with rVSV-ZEBOV 42 clusters (3528 people) were randomly assigned to

delayed vaccination with rVSV-ZEBOV Immediate vaccination group: no cases of Ebola virus

disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100%, 95% CI 74·7-100

No new cases Ebola virus disease diagnosed in vaccinees from immediate or delayed groups from 6 days post-vaccination

What virus is this?Putative sources of human epidemic: bites/scratches from, or eating the meat of, Bats or monkeys