Dr. Nicholas Miller, of Beremans Limited (www.beremans.com), and Ingelise Saunders, of ACE Biosciences AS (www.acebiosciences.com), discuss the growing need for and potential value in the development of a vaccine for Travellers’ Diarrhoea

Overview of Travellers’ Diarrhoea

Travellers’ Diarrhoea (TD) may arise as a result of infection by pathogens and is the most frequent health problem in travellers from industrialised countries visiting developing countries.

TD may be associated with significant disruption of holidays and business trips, as 30-45% of affected travellers may be obliged to modify their plans in some way.

TD may also cause chronic complications such as Reiter’s syndrome, an arthritic condition, and Guillain-Barre syndrome, a peripheral nerve disorder characterised by paralysis, which may leave patients severely impaired.

Furthermore, TD remains one of the most common problems encountered by deployed military personnel. Thus, among the 140,000 US military personnel recently deployed in the Middle East. 76% reported at least one episode of diarrhoea, and more than 50% reported multiple episodes.

Therefore, the high frequency of TD among travellers, the capacity of TD to significantly disrupt work / travel plans and the potential for development of serious chronic conditions, suggests that there is a need for effective products to prevent or treat TD.

Developing a TD treatment

Travellers often are advised to carry TD treatments in case of need. Products may be divided into those intended to control the infection (mainly antibiotics) and those which treat TD symptoms (anti-diarrhoeal agents).

Appropriate antibiotic therapy may reduce the course of TD from about three days to one day. However, the usefulness of the current range of antibiotics is limited by the spread of resistance among enteric pathogens.

This has obvious implications for therapy. For example, the difficulty in determining the causative agent when the patient is first seen, let alone the resistance profile of a given agent, necessitates a degree of trial and error in the treatment and often results in administration of inappropriate antibiotics.

This may have implications beyond treatment failure; in particular, not all antimicrobials are universally safe (for example, in the pregnant, in the elderly or in children), and some have the potential to select for pathogen virulence properties. In conclusion, although antimicrobial therapy is the best available treatment, it is not always beneficial.

TD prevention

Clearly, it would be preferable to prevent TD rather than to be obliged to treat it. Unfortunately, TD does not appear to be easily preventable by behavioural modification, and indeed TD is frequently contracted even when standard advice of avoiding high-risk food items (for example, ice, water and salads) is strictly followed.

Other preventive approaches include prophylactic antibiotics and vaccines. The consensus view is that antibiotic prophylaxis should almost always be avoided, partly because of the potential for side-effects.

Hence, the US Centers for Disease Control does not recommend antibiotic prophylaxis even for high-risk travellers. Given that travellers may develop disease despite their best preventive measures, a safe and effective TD vaccine would be desirable and efforts are underway to develop vaccines which would reduce the incidence of TD.

Demand for a TD vaccine

Demand for a TD vaccine is likely to be driven mainly by the extent of travel from significant economies to destinations at risk of TD. Below, we attempt to estimate numbers of travellers from significant economies visiting destinations at high or intermediate risk of TD. In brief, the main aspects of our methodology are as follows:

1. ‘Significant economies’ were defined as France, Germany, Italy, Netherlands, Scandinavia (comprising Denmark, Finland, Sweden, Norway) Spain, UK, USA, Canada, Australia, Japan, China and South Korea.

2. Data were collected on international tourist arrivals from each significant economy, using mainly World Travel Organisation sources. Data were used from the five-year period of 1999-2003.

3. The above data were rearranged to calculate arrivals from each significant economy to countries at, respectively, high or intermediate risk of TD. These data (1999-2003) were averaged to provide a baseline annual figure for market projections.

4. The figures for total reported arrivals were then revised downwards by the application of three factors:

The above process provided figures which suggest that between 1999 and 2003, an average of about 40 million visitors per year travelled from the significant economies to regions of high risk of TD. Similarly, between 1999 and 2003, about 48 million visitors per year travelled from the significant economies to regions of intermediate risk of TD.

We then extrapolated the above figures to provide figures for 2004 to the year 2020, using World Travel Organisation predictions for growth in international arrivals by region.

The number of travellers from significant economies visiting regions at high risk of TD would have been in the region of 45 million in 2005, and will reach 100 million travellers per year by 2020. The number of travellers from the significant economies visiting regions at intermediate risk of TD also would have been in the region of 55 million in 2005 and will approach 90 million travellers per year by 2020.

The bottom line

Current travel patterns suggest that in 2020 there will be about 100 million susceptible individuals travelling from significant economies to regions at high risk of TD.

Under current conditions, between 20 and 90% of these individuals would be expected to develop TD within 2 weeks of arrival. Similar numbers of individuals are likely to visit regions at intermediate risk of TD, and about 8-20% of these individuals would be expected to develop TD.

The potential for TD to significantly disrupt business and holiday activities, and at worst to result in severe chronic disease, suggests that a broadly effective TD vaccine would be useful for at least a proportion of these travellers.

However, the precise extent to which a TD vaccine will penetrate the above market is likely to be dependent on a number of factors.

For example, since travel vaccines in general are not mandatory, vaccine uptake is likely to be the result of a complex interplay between a physician’s willingness to recommend the vaccine and a traveller’s willingness to purchase the vaccine.

These in turn depend on criteria that may include the types of TD pathogens covered by the vaccine, the relative proportion of TD cases caused by these pathogens at a given destination, the price of the TD vaccine, the duration of protection provided by the TD vaccine, the effectiveness of the TD vaccine, the number and price of other desirable or mandatory travel vaccines, cultural attributes of travellers, perceptions of vaccines among travellers and the administration route / regime of the TD vaccine.

We have recently carried out original research in this field, including a survey of current attitudes among UK and US physicians (Miller and Saunders, in preparation). This work has allowed us to estimate the likely market penetration of proposed TD vaccines, and shall be the subject of future articles.

Questions and comments should be directed to Dr. Nicholas Miller at nm01@beremans.com

© Beremans Ltd. & Crimson Business Ltd. 2006