In this study we investigated the levels of anxiety and distress in travellers with an AAI over time, and identified which factors influenced these levels. Travellers experienced significant amounts of anxiety and distress after the AAI, especially women. PrEP, risk awareness, and WHO regions Africa and Central America were positively associated with increased anxiety directly post-AAI. After treatment, monkey-induced injury and injury in thoracic area, and region Southeast Asia were associated with less decrease in anxiety levels. Distress levels were positively associated with PrEP and WHO region Africa post-AAI, and after treatment with having a type II injury. A delay between 24 and 48 h was associated with more decrease in distress levels after treatment.

Uncertainty caused by sudden changes in everyday life may result in fear and anxiety. It is a known risk factor for significantly affecting mental health [29, 30]. In this study, a sudden event like an AAI caused anxiety among 60.5% of travellers, of which 19.2% reported severe levels. According to DSM-5, symptoms should persist for a longer time period to diagnose an anxiety disorder [31]. Although anxiety among travellers did not last long enough to be defined as a disorder, the burden did not disappear after treatment: the levels after treatment were still significantly higher compared to baseline (T1). Anxiety can have a profound impact as it is known to affect one’s behaviour, physiological and cognitive well-being [32], which are part of various quality of life (QOL) domains [32,33,34,35].

Nowadays, healthcare continues to evolve on many domains, resulting in a broader and more holistic definition of health. Health is more than absence of disease, it encompasses a wide range of contexts that cannot be expressed in money [36], emphasising the importance of health-related QOL (HR-QOL). Suijkerbuijk et al. [18] published a cost–benefit analysis for different rabies vaccination strategies in the Netherlands, but were unable to incorporate the cost implications in terms of HR-QOL. Such cost implications would be a valuable addition to the determination of health in contemporary society. Along with the increasing pressure on worldwide healthcare systems and expensive healthcare, the importance of HR-QOL is rising, thereby highlighting the significance of this study.

In line with previous research, women more often experienced anxiety and distress post-AAI. Previous research repeatedly demonstrated women to be more prone to develop anxiety and related mood disorders compared to men [37,38,39,40,41]. This trend is also visible through other health indicators given that women have more negative self-assessments of health, higher rates of sick leave at work, and make greater use of health services [42,43,44].

Having received PrEP resulted in higher anxiety and distress levels post-AAI counter to our expectations. Risk awareness also resulted in higher anxiety levels after the AAI. Having received PrEP could be accompanied with being aware of the risks of contracting rabies due to a visit to the vaccination clinic, which suggests that these factors are correlated. However, although not significant, the slope of the decrease at T3 is steeper for travellers with PrEP and risk awareness. This might suggest that even though anxiety levels for both factors spiked directly post-AAI, they also had a more reassuring effect than those without PrEP and awareness. Future studies should further investigate why travellers with PrEP are more inclined to anxiety.

In comparison to Europe, encountering an AAI in the WHO regions Africa and Central America was associated with increased anxiety after the AAI. After treatment, travellers to Southeast Asia had increased anxiety compared to those in Europe. This is in line with the assumption that not receiving RIG is associated with increased anxiety. It is known that RIG is difficult to obtain especially in Latin America and Southeast Asia. Travellers often need to travel to another country to receive RIG on time [8, 13], which increases the fear of risking a lethal infection.

Despite the sample size, contrary to our expectations, travellers with type II instead of type III had higher distress levels between AAI and treatment in comparison to type I. Although not significant, most monkey-induced injuries were type II, and none of the monkey-induced injuries was provoked. Travellers injured by monkeys compared to dogs were also more distressed. In Europe, monkeys only live in zoos. European travellers may therefore not intrinsically be aware of their potentially harmful behaviour and infections they may spread. Additionally, anxiety may be triggered even more in case of an AAI induced by a monkey, compared to one caused by a dog, which may be experienced as more familiar even for people without pets. This possibly also applies to bats but little travellers were injured by bats so no association could be found.

Interestingly, no elevated anxiety or distress levels were found for those with a PEP-delay. We found an association between PEP-delay of one day in comparison to no delay with more decrease in distress levels after treatment. Possibly, the decrease of distress levels is a natural phenomenon and given that distress was documented for a longer time period for those with PEP-delay between AAI and treatment, lower levels are to be expected. Nevertheless, this is in contradiction with other studies’ results who found increased distress in relation to treatment delay [45, 46]. A possible explanation could be a difference in risk awareness, but such analyses were off scope.

Our results imply that current pre-travel information and advice is no longer appropriate for the target group. Avoiding animal contact is fundamental to prevent rabies. However, nearly 90% of the travellers in this study encountered an AAI without provocation. Travellers with unexpected AAIs seem to be more anxious and distressed at T3, although not significant. As mentioned before, anxiety and fear are a result of uncertainty by a sudden event [30]. Stress often causes cognitive narrowing, hindering the patient from taking proper actions [47]. This could explain the spikes in anxiety and distress levels at T2 for travellers with PrEP, and also highlights the importance of pre-travel information. We believe that properly informing travellers about an AAI, its impact, the often limited availability of vaccines, and the required actions will give them a sense of control over the situation. Besides, psychological distress is known to be a wide concept which covers many emotions and psychiatric symptoms like depression and anxiety [48], suggesting that distress could be a precursor of anxiety. Tailoring information with the purpose of reducing or preferably preventing distress, and thereby anxiety, should avoid clinical levels [49]. This would be beneficial in terms of HR-QOL.

It is important that such information is received in the country of origin to reduce unnecessary distress. Apart from cultural differences, European travellers often speak different languages and are uncertain about local health care standards [47]. Information provided abroad might therefore not be fully understood, and local advice often differed from WHO guidelines [14]. Yet, the PrEP uptake in the Netherlands, indirectly referring to being informed, is relatively low [7,8,9,10]. Wieten et al. [10] found the costs and the limited time between consultation and departure to be prominent barriers in the decision-making process of PrEP. Expanding the window of time between consultation and departure might positively contribute to this decision-making process.

As for the costs, as pointed out earlier, health is no longer limited to absence of disease, but to a vaster concept of also mental health and lack of distress. Increasing awareness by improving pre-travel information might not give direct economic benefit, but is likely to increase HR-QOL. Since especially women suffer from anxiety and distress, prevention of those levels, or at least decrease, might also positively contribute to economisation by reducing sick leave and visits to healthcare providers. The experienced amount of anxiety and distress is barely expressible in an economic measure. Its lack, however, seems priceless.

This study is unique in addressing distress and anxiety in terms of a possible rabies infection due to an AAI. Self-reported anxiety and distress levels were measured by widely used and accepted measurement scales. Although we measured an anxious state of mind rather than a disorder, we were able to give insight into the impact of an AAI and how that relates to QOL. We believe that a simple intervention such as more targeted pre-travel information will prevent clinical anxiety levels.

Our study was limited in the sample size due to a relatively low and inconsistent response. This might be due to the unfortunate timing that coincided with the onset of the SARS-CoV-2 outbreak in the Netherlands. The AAI occurred up to four years ago at the time the questionnaire was dispatched. For this reason, recall bias might have overestimated our results as people often remember negative events more vividly [50]. Studying anxiety levels a few weeks after treatment, or a prospective study with multiple nationalities could have provided more accurate measures of the increase and decrease in anxiety. Last, although it does not yet exist, a measurement scale that measures a short-term state of mind would have matched the study better.

We recommend replicating this study prospectively with a different scale to measure state of mind with a larger study population, and a longer follow-up period after treatment administration. We think this will increase the response rate, and gives the opportunity to investigate more associations. It would be insightful to be able to measure QOL at baseline and after the AAI as well. This would provide opportunities for calculating intangible costs related to an AAI. Furthermore, we highlight the importance of targeted information before travelling, which effects could be studied in an intervention study.