Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 11th Conference of the International Society of Travel Medicine

Budapest, Hungary / May 24-28, 2009

“Japanese encephalitis [JE] is the leading cause of viral encephalitis throughout Asia, with devastating consequences for travellers, and there is no effective treatment for it,” according to Dr. Tomas Jelinek, Berlin Center for Travel and Tropical Medicine, Germany. Patients will suffer a general viral syndrome of fever, headache and other non JE-specific signs for three to seven days. A few develop inflammation of the brain and a variety of focal neurologic deficits leading to more severe symptoms and coma. Dr. Jelinek added that about one-third of patients die and one-third recover but have sequelae that persist for a lifetime. Non-fatal cases require a long and debilitating period until recovery.

“The drawback is that we cannot react as clinicians once the disease has settled. We can treat only in a symptomatic way,” he stated. “We should inform all travellers to endemic regions of Asia about the risk and consequences of JE and recommend the newly available, vero-cell-derived inactivated vaccine to all expatriates, repeat travellers and those wanting maximum protection. Even individuals travelling for a short time to rural areas should at least be informed of the risks and the potential interventions.”

According to Dr. Jelinek, with the launch of an effective new vero-cell-derived JE vaccine, many travel medicine experts now believe most travellers to Asia should be vaccinated against JE.

New Developments in Protection

Reviewing the clinical profile of the new JE vaccine, which was approved for use in the US in April 2009, Dr. Elaine Jong, University of Washington School of Medicine, Seattle, observed that because it is not derived from mouse brain, the fear of potentially adverse reactions with the old JE vaccine has been effectively eliminated. The new inactivated vaccine is based on virus strain SA14-14-2 cultured in vero cells. The formulation does not include preservatives or the porcine gelatin stabilizers believed to be responsible for severe side effects, including anaphylaxis, observed with use of the previously available Biken formulation.

“The new vaccine has been shown in clinical trials to be highly immunogenic after doses given on days 0 and 28, resulting in seroconversion of 98% by day 56,” she noted. “The second dose has been shown to result in a rapid increase in serum-specific protective antibodies far in excess of the minimum needed to protect against JE virus, with a seroconversion rate of up to 97% in as few as seven days. This suggests that the vaccine could be given even when there is not much time before departure of the traveller to a high-risk region. There will be no delayed hypersensitivity or other serious reactions,” Dr. Jong added. “The vaccine is very well tolerated with no difference between active vaccine and placebo.”

Follow-up studies demonstrated good persistence of immunity, with 95% of individuals retaining protective antibody titres six months following immunization and 83% after one year, Dr. Jong reported.

From a Canadian perspective, the new vero-cell-derived JE vaccine is an important advance in travel vaccines, according to Dr. Jay Keystone, Director, Medisys Travel Health and Immunization Clinic, and Professor of Medicine, University of Toronto, Ontario. “Although JE is a rare problem in travellers to rural Southeast Asia, potentially it is a very severe infection that has been associated with up to 25% mortality and 50% residual neurological damage in those with the disease.” The new vaccine requires only two doses and was better tolerated in comparative safety trials, Dr. Keystone commented. He also observed that the new vaccine has the same high rates of seroconversion and antibody titres as the old vaccine, adding that the new vaccine will soon be the only JE vaccine available to protect travellers against this important infection, as production of the old formulation is being phased out.

Meningococcal Vaccine for Travellers

As observed by Dr. Annelies Wilder-Smith, National University Hospital, Singapore, “Meningococcal disease is often neglected in travel medicine recommendations despite the fact that 500,000 cases occur globally every year.

Even with timely and appropriate treatment, case fatality rates are 10% to 14% and up to 20% of survivors suffer permanent sequelae,” she told delegates. “The risk of infection is enhanced by crowded conditions with close person-to-person contact, such as at the hajj pilgrimage, when two million Muslims visit Mecca, and in the meningitis belt of sub-Saharan Africa from Senegal to Ethiopia; serogroup W135 has recently emerged in those regions.”

Dr. Wilder-Smith added that the drawbacks of traditional polysaccharide vaccines include limited duration of protection requiring booster dosing with the added risk of hypo-responsiveness; they do not reduce carriage rates and are not immunogenic in children under the age of 2 years.

The currently available multivalent conjugate vaccines have a better immune memory, longer duration of protection and a booster effect. They reduce virus carriage in the naso-pharynx, thereby contributing to herd immunity, and eliminate the problem of hypo-responsiveness with repeated dosing. One month after primary immunization, immune response rates range from 83% against serogroup A to 99% against W-135.

Rabies Prevention

According to experts here, two facts distinguish rabies from all other vaccine-preventable diseases. The exact time and source of exposure are almost always known and the disease can almost always be prevented by post-exposure immune therapy.

To Dr. David Shlim, Medical Director, Jackson Hole Travel and Tropical Medicine, Wyoming, that means that the prevention of rabies in travellers is primarily an educational and logistical problem. He said that deaths have been recorded, but when patients die it is because they did not seek prophylaxis, did not know where to get treatment or the treatment they ultimately received was not ideal. However, no deaths have occurred while obtaining appropriate post-exposure prophylaxis, he said.

Noting that 96% of the risk of rabies is from dog bites, Dr. Shlim provides travellers with a “fairly detailed” checklist of measures to follow when bitten by a possibly rabid animal, including washing the wound copiously with soap and water and applying povidone-iodine topical antiseptic. If pre-immunized, the individual should find a source of modern cell culture rabies vaccine to be boosted with on days 0 and 3. Individuals not previously immunized would receive one dose of human rabies immune globulin (HRIG), even if they have to return to North America to get it, and five doses of rabies vaccine in a 28-day period (days 0, 3, 7, 14 and 28).

Dr. Shlim said that there are certain benefits to pre-exposure prophylactic immunization in this scenario. HRIG is not required following exposure to rabies because it is contraindicated when booster vaccine is given. That gives the traveller some latitude because HRIG is in short supply in some parts of the world and is a limiting factor for international travel. Additionally, post-exposure prophylaxis is reduced from five doses of vaccine to two, the treatment period drops from 28 days to three, and the overall expenditure for post-exposure treatment is reduced. There is a safety margin built into pre-exposure immunization in that no one who has later been boosted after exposure has ever developed rabies.

Dr. Shlim characterized the rabies virus as unique in that it does not enter the blood or lymphatic system. It stays in the skin or muscle until taken up by the neurons and carried to the brain within a day or two. Once in the nerve, it is shielded from the immune system, so the treatment goal is to prevent the virus from getting into the nerve. “We used to think that closer to the brain increased the risk, but it is really closer to the nerve. This is how you prevent rabies in travellers,” Dr. Shlim concluded. “It is an educational and logistic issue rather than a medical one.”

In Canada, a rabies vaccine is available for pre-exposure immunization and post-exposure prophylaxis. Pre-exposure immunization should be offered to children and adults who are at high risk of rabies exposure. This group would include international travellers visiting areas where rabies is endemic and appropriate post-exposure treatment may be delayed or unavailable as well as those whose work or hobbies bring them in contact with the rabies virus or potentially rabid animals.