13-Oct-15. This Traveller. Some travellers are at a higher risk of VPDs

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1 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 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 1

2 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 International health regulations. 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 symptoms fever, 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, * Data (Zwar 2003) 2

3 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 required 4 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 death Case-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.. 3

4 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 & 5 taken 1 hr before food A 4th dose (day 7) can also be given Vivaxim 16yrs Single dose For 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. typhi On-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 4

5 Quadrivalent meningococcal conjugate vaccines (4vMenCV) Nimenrix 1 55 years Menactra 2 55 years Menveo 11 years Quadrivalent meningococcal polysaccharide vaccines (4vMenPV) Mencevax ACWY Menomune >2 years >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 Source: McIntosh 28 D. Presented at: 2013 Vaccine Preventable Diseases Conference; April 2013; Dublin, Ireland. Available at: (accessed Mar 2014) New Men B vaccine licensed in Australia Today: Happy but happier if she had been vaccinated Will the vaccine be recommended for routine use? 5

6 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 6

7 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 Live attenuated JE virus Imojev 1 yr Single dose SC injection into deltoid Inactivated JE virus JESPECT 18 yrs 2 doses: days 0 and 28, IM injection deltoid 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) 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 What % of mammals? What diseases? Booster: single dose up to 2 years after primary course completion If longer, repeat primary immunisation 7

8 Rabies The fearless folly of youth Almost invariably fatal if not treated Order: Chiroptera Suborder: Megachiroptera ("megabats") Family: Pteropodidae (flying foxes, Old World fruit bats) Transmits Hendra, Lyssa 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, Hanna JN et al. Australian bat lyssavirus infection: a second human case with a long incubation period. MJA 172,

9 1 st cases reported in Indonesia in 1884 present in 24 of 33 provinces Bali from 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 Clinical Microbiology and Infection Volume 17, Issue 3, pages , 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 Clinical Microbiology and Infection Volume 17, Issue 3, pages , March Mosquitos trapped in amber Origin: Gorillas Liu et al Nature 2010 Human P Falciparum forms monophyletic lineage within gorilla parasite radiation Increasing drug and insecticide resistance Complicated lifecycle, Ags expressed at different stages Malaria genome sequenced 5300 gene products ( many potential targets) 630,000 deaths/year mainly children, 90% in Africa 200 million people infected by P falciparum 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? 9

10 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 Efficacy and effectiveness of an rvsv-vectored vaccine expressing Ebola surface glycoprotein: interim results Guinea ring vaccination clusterrandomised trial Lancet 2015 Aug million lives saved in 20 th 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 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-Guinée were 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 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 10