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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 - 8th Northern European Conference on Travel Medicine (NECTM8)

Rotterdam, The Netherlands / June 8-10, 2022

Rotterdam - According to investigators here this week, climate change is one of the key drivers of the emergence, re- emergence  and  spread  of  infectious  disease.  Vector-borne  diseases  are  mainly  transmitted  by  mosquitoes  which  are particularly  sensitive  to  global  warming  but  changes  in  the  environment  created  by  human  behavior  combined  with international  travel  cannot  be  underestimated  as  key  contributors  to  the  spread  of  mosquito-borne  diseases,  including Japanese encephalitis (JE), dengue fever and chikungunya. Comprehensive JE vaccination programs exist in many parts of the world, but travellers to endemic areas risk becoming infected themselves. Similarly, those who visit regions of the world where chikungunya is endemic are also at risk for infection and worse, risk bringing the disease back home where others will be infected; promoted by both climate change and urbanization, chikungunya is emerging in countries where it has never been seen before. Since avoiding getting bitten by mosquitoes is difficult, one of the best protection against infection is to be vaccinated against the diseases mosquitoes carry. Several new vaccines targeting mosquito-borne diseases are in development.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

JE Virus 

Japanese encephalitis (JE) has long been an important public health issue throughout Asia, where it is the leading cause of viral encephalitis and neurological disability. An estimated 68,000 people develop symptomatic JE every year. Although rare, if people do become symptomatic, approximately one-third will die; of those who do survive, approximately half are disabled for life. According to scientists, pigs and birds are the reservoir hosts for this infection and when animals get infected, “mosquitoes feed on them and infect other mosquitoes and around the cycle goes,” Dr. Johanna Lindahl, Swedish University of Agricultural Science, Uppsala, Sweden, told delegates.

Vaccination is common in most countries where JE is endemic, as Dr. Lindahl noted. Where vaccination programs have been implemented, they have been highly successful for example, the incidence of JE in China dropped by 98% following the launch of their vaccination program. However, even if every single child in an endemic area were vaccinated against JE, the immunologically naïve would never be protected against the infection and a single bite could do it, she stressed. 

Since there is a vaccine to protect travellers from JE, Lindahl suggests that people planning even a short trip to Asia, India and most recently, Australia where JE has unfortunately now appeared in some regions, assess what their risk might be of becoming infected with JE. (Dr. Lindahl stated she, herself would personally get vaccinated if she were to visit a country where JE is endemic). If a traveller doesn’t feel they are at high enough risk to be vaccinated, they still need to protect themselves against mosquito bites, be vigilant with  mosquito repellent, wear long-sleeve clothes, use bed nets, anything that makes it more difficult for mosquitoes to make contact.

“Basically, these are the only ways that people can protect themselves [against mosquito bites] because they are not protected by the local vaccination campaign,” Dr. Lindahl reemphasized. “Remember that the main reason that has allowed mosquitoes to spread is humans making changes to the environment —that is why we are seeing these diseases spreading,” she explained. 

Dengue Virus 

Dengue fever is the fastest spreading mosquito-borne viral disease and as such, is a major threat to global health. Dengue is mainly spread by several strains of the Aedes mosquito and is caused by any one of four dengue virus serotypes. Endemic in tropical and sub-tropical areas, recovery from infection by one serotype provides lifelong immunity against only that serotype so the risk of severe disease persists in case of exposure to the remaining serotypes.

All that may soon change according to updates presented here on emerging evidence for a new vaccine against dengue,  according to Mr. Vianney Tricou, a clinical development professional specialized in infectious diseases at Takeda International. The candidate vaccine, tetravalent TAK-003, is based on a live-attenuated dengue serotype 2 virus vaccine which provides the genetic “backbone” for all four vaccine viruses.  It has been shown to prevent hospitalizations due to dengue and overall illness compared with placebo.

The Tetravalent Immunization against Dengue Efficacy Study (TIDES) involved over 20,000 healthy children and adolescents between 4 and 16 years of age living in dengue- endemic areas. Participants received their first dose of the TAK-003 candidate vaccine on day 1 and the second dose on day 90. “The study had very good retention rate with 91% of participants remaining in the study for 4.5 years of follow-up,” Mr. Tricou reported during the meeting.

For the entire 4.5-years of follow-up, vaccine effectiveness (VE) against hospitalization from dengue remained high at roughly 90% while VE against all illness was approximately 61%. This held true for both seronegative and seropositive patients at baseline and the difference between placebo and vaccine recipients continued to diverge over time— demonstrating continued efficacy of the vaccine, as Mr. Tricou told delegates.

Indeed, modelling studies indicate that between 4400 and 5000 cases of dengue illness would be prevented for every 100,000 vaccine recipients, depending on whether they were seronegative or seropositive at baseline along with 1800 hospitalizations for dengue in the same 100,000 vaccine recipients. “Adverse events in those who received the vaccine were not higher compared with placebo and there were no new safety-related signals,” Mr. Tricou said. Adding “and in the program overall, over 20,000 recipients have received almost 40,000 doses of the vaccine.” 

Chikungunya Virus 

Like the dengue virus, the chikungunya virus is also transmitted by infected Aedes mosquitoes. Originally found mainly in Southeast Asia and East Africa, the virus has now spread to over 100 countries, the first outbreak in Europe occurring in

2007 in Italy, before the real onset of climate change, as noted by Dr. Tomas Jelinek, Berlin Center for Travel and Infectious Disease, Germany. The threat posed by chikungunya virus could be increased by climate change because rising temperatures will favour the distribution of the vector and thus the disease, increasing geographical distribution and size of the population at risk of infection. “The vector is spreading because we provide habitation for it, dumps, slums, and breeding grounds for mosquitoes and once a vector is present, you just need1 human who is viremic and then you can start an outbreak,”he told delegates.

When an outbreak occurs, one-third to three-quarters of the population in areas where the virus is spreading become infected as well “so there is a high attack rate and most people develop symptoms,” Dr. Jelinek reported.  Symptoms primarily include fever, joint pain and arthralgia at least acutely, but for many patients, the joint pain evolves into long-lasting painful joints similar to rheumatoid arthritis, long-lasting muscle stiffness and chronic inflammatory signs.

There are no treatments for either the acute or the chronic stage,” Dr. Jelinek stressed, “so the only thing we can do when we counsel travellers is not to get bitten by a mosquito which is not easy to achieve,” he acknowledged. This, too, may soon change, as several vaccines are currently under development (see Table 1). The results from a phase 1 study which is published and an as yet unpublished phase 3 study from one of the  candidate chikungunya vaccines under development were presented at the conference and shown to be  immunogenic.

In the phase 1 study (Lancet Infectious Diseases. 2020;10:1193-1203), the seroconversion rate at day 14 following a single shot of the candidate vaccine was 100%. Sustainable and high titres of neutralizing antibodies were  maintained up to 12 months and the vaccine was well tolerated.

Recently, a pivotal phase 3 trial was completed, in which a single shot of the chikungunya vaccine candidate was again evaluated. At day 28, the seroprotection rate was 98.9% which met the primary endpoint of the study. This was maintained at month 6 when the seroprotection rate remained high at 96.3%.Equally high geometric mean titres were achieved among recipients regardless of age, as Dr. Jelinek noted. The results were consistent with those seen in the earlier trial and findings are expected to be published in the near future. 

Summary 

For two long years, travellers have been asked to stay home to avoid becoming infected with COVID-19. Now that the pandemic is abating, travel is picking up again and the likelihood of someone becoming infected with formerly “exotic” diseases, especially if visiting tropical and sub-tropical regions of the world is relatively high. According to researchers here this week, it takes only one or 2 viremic travellers to bring the virus back to an immunologically “naïve” region where it can rapidly spread, especially in the case of the chikungunya virus. Fortunately, vaccine scientists are meeting the challenge of protecting people against these infectious threats. More research is needed. Now, it is up to those who counsel travellers to alert them to the real risks of acquiring what can be a devastating infection and to the possibility that further protective measures are emerging on the horizon, as promising new vaccines become available in the future.   

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