Nepal is a popular destination for adventure travellers, cultural tourists, wildlife enthusiasts, and pilgrims. An average of 719,117 tourists visited Nepal annually from 2009 to 2017, with a mean duration of stay of 12.6 days [1]. Since 2018, Nepal has hosted over 1 million tourists annually, with an increasing number of travellers coming from within Asia [1,2]. A slight decline in tourism occurred during the earthquake of April 2015; however, tourism rebounded in 2016 [1].

There are 2 seasonal peaks in tourism when the weather is favourable, occurring in the spring (March–April) and the fall (October–November). Previous studies have shown that the risk of enterically-transmitted diseases is increased in the spring relative to all other seasons [3]. Although numerous papers describe individual risks to travellers to Nepal, including altitude illness, diarrhoea, cyclosporiasis, enteric fever, rabies, and hepatitis, a comprehensive analysis of diseases reported among travellers in Nepal has not been published.

The CIWEC Clinic in Kathmandu was founded in 1982 with a mission to provide medical care to expatriates working for the Canadian International Water and Energy Consultants (CIWEC) project in Nepal. The clinic became the first destination travel medicine clinic in the world, and evolved into a hospital [4] providing care to expatriates and travellers to Nepal as well as to the local Nepali population [5]. CIWEC joined the GeoSentinel surveillance network in 1998 [6,7].

The aim of this analysis was to provide a comprehensive summary of diseases acquired by international travellers in Nepal over a 9-year period. Using data from CIWEC, the largest infectious diseases centre catering to travellers in Kathmandu, the findings of this analysis can be used to strengthen pre-travel counselling and recommendations for travellers to Nepal.

There were 24,271 records included (annual mean: 2,662 travellers) with 29,281 diagnoses. The median age was 30 years (range: 0–91); 54% were female. Travellers were most frequently tourists (63%), business travellers (20%), and missionaries, volunteers, or humanitarian aid workers (14%). The median trip duration was 16 days. Eight percent were hospitalized; there were 6 deaths. Travellers were most frequently born in the United States (18%), the United Kingdom (11%), Australia (8%), and Germany (6%). The most common systems-based diagnosis groups included: GI, pulmonary, dermatologic, HEENT, neurologic, musculoskeletal, GU, and febrile syndromes.

Diagnoses among travellers to Nepal seen at CIWEC are in Table 1.

This analysis provides a description of over 24,000 ill travellers who presented to CIWEC in Kathmandu over 9 years. CIWEC has the highest volume of travellers in both the GeoSentinel Network and in Nepal, making it ideal to describe the spectrum of travel-related illnesses. The strengths of this report are in the large number and longitudinal perspective as well as patient care by practitioners experienced in travel medicine which validates the diagnoses. Given increasing travel to Nepal in recent years, knowing the frequency of travel-related illness among travellers to Nepal is necessary to optimally prepare international travellers before arrival.

Gastrointestinal illnesses, including acute diarrhoea, were the most frequently reported diagnoses for which travellers sought healthcare at CIWEC while visiting Nepal. The aetiology of diarrhoea in travellers and expatriates has been studied systematically at CIWEC in various publications [3, 9–11]. Acute diarrhoea accounts for a significant proportion of illnesses faced by travellers to many developing countries and regions of the world [12–15]. Bacterial aetiologies of acute diarrhoea predominate in Nepal, though recent comprehensive molecular analyses demonstrated that the top 3 pathogens are Campylobacter, Norovirus, and Shigella [3, 9–11]. Near-total bacterial resistance to fluoroquinolones has been documented for nearly a decade in Nepal and azithromycin has become the drug of choice for moderate to severe bacterial diarrhoea [10, 11]. Our study was unable to determine how many travellers self-diagnose and treat travellers’ diarrhoea, or whether travellers have failed self-treatment.

Parasitic pathogens are typically less frequent among travellers in Nepal with diarrhoea, however, this analysis demonstrates large numbers of parasitic pathogens, such as giardiasis and cyclosporiasis. Cyclosporiasis infections have remained steady in recent years in Nepal; the coccidian parasite that causes cyclosporiasis is only present in Nepal from May to September, a time of decreased tourism [16], which may explain why approximately one-third of cyclosporiasis infections in this analysis were diagnosed among long-term travellers or expatriates.

Nepal remains one of the highest risk destinations for enteric fever globally, complicated by increasing drug-resistance [17]. Typhoid vaccine is recommended for international travellers visiting Nepal but is not required [18]. A study in Nepal suggested that the typhoid vaccine may have been more protective in travellers than in local people [19]. The authors postulated that travellers taking food and water precautions may experience lower exposure to S. Typhi, allowing the vaccine to be more effective. However, typhoid vaccine efficacy studies performed in local populations demonstrate between 48 and 80% protection depending on the population studied, so best practices for prevention of typhoid fever among travellers to Nepal include vaccination in addition to safe food and water precautions [20,21]. A conjugate typhoid vaccine is now available that was found to be 81.6% effective when studied in Nepali children [22] and should be recommended to the paediatric and VFR traveller visiting South Asia including Nepal. Nalidixic acid (NA) resistance is a good marker for fluoroquinolone (FQ) resistance and there is increasing NA resistance in enteric fever cases in Nepal [23,24], hence the use of FQs for treatment of enteric fever in travellers to Nepal ought to be discouraged.

Altitude illness is a preventable condition, but cases continue to occur including deaths due to severe altitude illness [25,26]. Among cases of altitude illness seen at CIWEC during the study period, half were severe (HAPE or HACE). Everest area trekkers and climbers are known to suffer the most from altitude-related conditions, needing helicopter evacuations [27]. Despite resources available to trekkers [28], basic knowledge about altitude illness symptoms, prevention, and treatment remains low and less than 50% of Himalayan trekkers are adequately prepared for prevention prior to their journey [29]. Notably, altitude illnesses were the 2nd (HAPE) and 3rd (AMS) most common aetiology of illness among travellers >70 years of age. This suggests that the elderly may also be prone to altitude-related illness [30] and special consideration should be given to them in pretravel counselling to ensure they are aware of prevention measures, including chemoprophylaxis and gradual ascent.

Frostbite occurs regularly in Nepal when mountain climbers and trekkers get trapped in bad weather conditions. Frostbite occurred exclusively in tourist travellers, as was seen in a previous CIWEC study [31]. The prostacyclin analogue Iloprost has been used in Nepal in Himalayan climbers with severe frostbite with promising results [32]. Tourists who travel to Nepal from warmer climates need pretravel education on frostbite prevention, including wearing appropriate clothing and footwear, staying hydrated, and limiting their time outdoors in cold weather.

Many travellers in this analysis presented to CIWEC after an animal bite or exposure and required receipt of rabies post-exposure prophylaxis (PEP). Rabies vaccine for PEP is available in Nepal; human rabies immune globulin (RIG) is available in specialty clinics in Kathmandu but it is not widely available throughout the country. This may pose an issue for travellers outside of Kathmandu that have animal exposure if they are unable to travel to a specialty clinic. Since rabies can be found in various mammals in Nepal, travellers involved in outdoor activities, people working with or around animals, and people who are long-term travellers should be offered rabies pre-exposure prophylaxis [18] which negates the need for RIG and simplifies the post-exposure vaccine regimen [33]. Monkeys have also been found to have rabies in the Indian subcontinent and South East Asia [34,35]. It is advisable to provide PEP against rabies after monkey bites [35,36]. With intradermal rabies vaccine becoming more widespread in use and increasing acceptability of the new WHO recommendation [37] of a 2-dose series for rabies pre-exposure (PrEP), the cost of rabies PrEP (seen as a barrier in parts of the world, including the United States) may be more acceptable to travellers.

Recent reports of vector-borne spread and increased vector-borne disease, especially dengue, have been reported among the local population in the face of global warming and increased population mobility [38–40], but few cases of vector-borne diseases were reported in this analysis, especially those that were locally acquired. Almost all malaria cases and most dengue cases were imported, suggesting that these diseases may not be frequently acquired by travellers to Nepal. Travellers typically visit Kathmandu and are less likely to visit the areas of the country, especially the low-lying Terai, that are endemic for JE and dengue. However, with the spread of mosquitoes to higher elevation, this is likely to change, as is evidenced by reports in 2019 of a dengue outbreak in the Kathmandu Valley [41].

Locally-acquired rickettsial infections, especially R. typhi, which are a cause of febrile illness among the local population including Kathmandu [42], were rarely reported. Despite 120 reported tick bites, tick-borne rickettsiosis diagnoses were low; just one case of Rickettsia honei infection (exposure in Kathmandu) was reported during this period [43]. Scrub typhus and murine typhus have been reported during the evaluation of febrile Nepali patients in a hospital-based setting [44, 45], and scrub typhus in serum samples obtained from febrile patients in a laboratory setting [46]. Travellers to Nepal should maintain awareness of the prevalence of rickettsial diseases in Nepal, especially if planning to work or live among the local population.

This analysis includes the first reported case of JE in a long-term traveller to Nepal [47]. Vero cell vaccine (JE-VC), recombinant chimeric virus vaccine (CV-JE) and live vaccine of SA 14–14-2 (Chengdu) strain (JE-LV) are available in Nepal to international travellers for prevention of JE [48]. This case highlights the importance of JE awareness and vaccination among travellers to Nepal, particularly for those traveling long-term.

It is likely that some travellers diagnosed with undifferentiated febrile syndromes reported in this analysis may have been ill with a vector-borne disease, such as murine typhus [49]; molecular studies are underway to improve fever diagnostics at CIWEC and are expected to help define the frequency of vector-borne disease among travellers with fever in Nepal.

Despite the representativeness of CIWEC’s data for travellers to Nepal, this analysis has limitations. These data are not population-based, so rates and risks cannot be determined. Vaccination history is not routinely collected and classification of a diagnosis as confirmed or probable is reliant on case definitions and clinical expertise.

Travellers to Nepal may acquire a variety of infectious and non-infectious diseases and conditions during travel in Nepal. Pretravel preparation for travellers to Nepal should include a pretravel consultation with a healthcare provider who can administer appropriate recommended vaccinations and provide education about the unique risks based upon their itinerary. These recommendations should include education about prevention and self-treatment of traveller’s diarrhoea; advice about altitude illness including recognition, prevention, and treatment; instructions on how to avoid animal exposures, emphasizing the need for PrEP and PEP; and protection from insect and arthropod bites including available vaccinations.