Out of a total of 1215 travellers who attended the HTD travel clinic between 1st April 2019 and 30th April 2020, 218 potentially immunocompromised travellers were identified. Of these, 25 patients were excluded; 13 were immunocompromised but were not travelling (seven attended for a pneumococcal vaccination; one for a re-issue of a yellow fever certificate, and five for annual or post-deployment medical). Eleven were immunocompetent, inaccurately captured owing to non-systemic immunosuppressants and one traveller’s details could not be retrieved. A total of 193 travellers were included. The ratio of male to female was 0.75 (83/110); median age; 38 (range 9 months to 84 years). ICTs planned trips to 80 different countries. The top 10 most visited countries were Brazil (n = 22), Kenya (n = 19), Ghana (n = 17), Peru (n = 13), Tanzania (n = 13), Thailand (n = 12), India (n = 11), Argentina (n = 11), South Africa (n = 9), and Nigeria (n = 9). Generally, ICTs in our clinic were travelling to East and West Africa (19% and 18% respectively), South America (16%), South Eastern Asia (11%) and Southern Asia (8%). Around one third (n = 62, 32.6%) ICTs planned to visit more than one country. Travel duration ranged considerably, from 2 to 3167 days, with a median duration of 16 days. Figure 1 outlines the primary reasons for travel among ICTs. (See supplementary index for detailed summary of demographics by reasons for travel).

Distribution of primary reason for travel

The distribution of IC is shown in Table 1. Most ICTs had secondary immunocompromise (97.9%) and amongst these the most common reason was physiological (42%), followed by chronic infectious inflammatory conditions (17.1%). Immunocompromise due to treatment with immunomodulating and suppressive medications accounted for 16.6%. A tiny minority (2.1%) had primary immunodeficiency.

Travellers were taking a wide variety of immunosuppressive medications (Table 2). Fifty seven ICTs were taking as many as 23 different immunosuppressive drugs including nine ICTs who were taking two different medications and 1 ICT who was taking three different medications. Five patients were either taking steroids as part of multi-drug regimen, or as a single immunosuppressive agent at a moderate to high dose [18].

Just three international travel medicine guidelines (Green Book, IDSA, CDC) categorise ‘severity’ of immunocompromise [7, 18, 19, 24, 26]. Stratification is based on live vaccine risk, and does not at present, incorporate risk of acquiring opportunistic infections or condition-related complications. Due to this limitation, we stratified our cohort on this basis. (Tables 3 and 4). The mild ICT group may be considered eligible to receive live vaccination with qualifications, whilst the cohort of severely ICT will almost never be given live vaccines.

Table S5 (Supplementary Index) compares the grading categories across the guidelines. CDC, IDSA and the Green Book (UK) largely align, but we found that the Green Book and IDSA do not provide detail to differentiate risk between different individual biologics, and whilst most conditions are grouped, some are not directly mentioned. The vaccine risk profile of a tyrosine kinase inhibitor such as nilotinib, being taken by one of the ICTs in our study, is not discussed specifically in any of these 3 published vaccine safety guidelines. Myeloproliferative diseases such as polycythaemia rubra vera are not highlighted. We have categorised this individual as severe due to having a haematological neoplastic disorder. Some discrepancies exist between sources in the definition of risk period following solid organ transplantation (SOT) and chemoradiotherapy. There is some ambiguity in the context of multiple sclerosis; CDC guidance highlights interferon as a therapeutic agent that confers severe immunocompromise but notes it is considered immunomodulation by specialists and therefore would not be contraindicated in live vaccination. The definitions of ‘high’ dose immunomodulation for individuals taking azathioprine, methotrexate, mercaptopurine and corticosteroids align across all sources [18].

In this study, no severely ICT at time of appointment, according to our list, were given live vaccines. We have highlighted conditions that the guidelines do not cover and additional study subgroups in grey.

Out of 193 ICTs, 2.1% (n = 4) were advised against travel. Half (47.7%, n = 92) of all ICTs were travelling to malaria endemic areas and were issued malaria chemoprophylaxis. Of these ICTs, 39.1% (n = 36) were ‘special category’ individuals requiring second-line prophylaxis due to pregnancy, breastfeeding, age < 2 years, and potential drug-to-drug interactions [27].

About a fifth of ICTs (18.7%, n = 36) had serology testing. The most frequently offered vaccination was hepatitis A (n = 49), rabies (n = 40) typhoid (n = 34), pneumococcal (n = 34), diphtheria tetanus and polio (n = 33), yellow fever (n = 21), meningitis ACWY (n = 12), hepatitis B (n = 12), and measles mumps rubella (MMR) (n = 7). MMR and YFV was contraindicated in five and 28 ICTs respectively due to severe immunocompromise at time of appointment. Additional vaccinations such as Japanese encephalitis virus (n = 8), tetanus (n = 6), meningitis B (n = 3), Haemophilus influenzae B (n = 3), human papilloma virus (n = 2), cholera (n = 2), meningitis C (n = 2) were given to a small fraction. Discussion surrounding rabies or pneumococcal vaccine was not consistently documented to understand the extent to which these were considered across the cohort. Additional individualised considerations included issuing medic-alert bracelets, discussion about risk of tuberculosis exposure, and the logistics of maintaining a cold chain for transporting medicines were relevant for 13.5% (n = 26) of all ICTs. Just 10.4% (n = 20) of all travellers were issued rescue pack antibiotics (immunomodulated inflammatory rheumatological conditions n = 7, haematological malignancy n = 5, multiple sclerosis n = 2, HIV n = 2, diabetes n = 1, solid malignancy n = 1, SOT n = 1, primary immunodeficiency n = 1).

Of the 48 severely ICTs, 6.25% (n = 3) were advised not to travel. The first was an individual with a primary immunodeficiency travelling to India for a non-medical work trip. The second individual was significantly immunosuppressed with a TNF inhibitor for juvenile arthritis, primary immunodeficiency, and neurological co-morbidities, travelling to Pakistan for a mass gathering. The third traveller had clinically active autoimmune eye disease who had just commenced mycophenolate, travelling to Vietnam for leisure.

Live vaccine safety dominated the documented clinical discussion and reasons for attendance. This included discussing the timing of (re-vaccination schedule after haemopoietic stem cell transplant or biologic therapy, serology testing or YFV exemption or vaccine contraindication discussion.

YFV was contraindicated for all 10 travellers visiting yellow fever endemic areas. These travellers were exempt due to history of thymectomy (n = 1), taking a TNF inhibitor (n = 1), natalizumab (n = 2), HCST within 24 months (n = 1), taking ustekinumab (n = 1 where timing of yellow fever was discussed for three months after they stop taking this monoclonal agent), recent high dose steroid courses (n = 1, YFV was discussed after disease had stabilized), cladribine (n = 1), and high dose mycophenolate (n = 1).

MMR vaccination was contraindicated in five severely ICTs travelling to Australia, Canada, Colombia, Sri Lanka, United Arab Emirates and Thailand. Three had a haematological malignancy; one was < 2 years post-HSCT, one was < 2 years post- chimeric antigen receptor T-cell (CAR-T) therapy and one was < 6 months post rituximab treatment. One was taking a TNF inhibitor and one had primary immunodeficiency post-HCST without full immune reconstitution. Two of these ICTs had no residual measles immunity (“IgG negative”). One was able to have an MMR prior to departure, as this was beyond the two-year mark, and the other ICT was advised they could travel but to avoid mass gatherings. The remaining three had residual measles antibodies on serology. The ICT six months-post rituximab was advised with small delay he could receive MMR prior to travelling to Colombia.

A fifth had additional discussions around cold chain management in the context of transporting insulin, and adalimumab. Approximately a third received antibiotic rescue packs.

Of the 145 mildly ICTs, one pregnant individual travelling to Uganda for non-medical work was advised against travelling. The YFV was contraindicated or exempt for just under half (46.2%, n = 18) of the 39 mildly IC travellers visiting areas with potential yellow fever risk. Exceptions were given based on age < 2, or > 60 with or without additional co-morbidities, clinically active eye disease, pregnancy, and an individual living with HIV with a high viral load. Of the 21 travellers who received the YFV, individuals were 60 or over (n = 4); without co-morbidities (n = 2), and with co-morbidities such as coeliac or diabetes (n = 2), individuals between 6 months and 2 years old without underlying health conditions (n = 2), or with sickle cell disease (n = 1), aged 18–59 living with virologically supressed HIV CD4 > 200 (n = 7), sickle cell disease (n = 3), diabetes (n = 2) or on low dose antimetabolites (n = 2).

The MMR vaccine was offered to seven individuals in the mild group. This was as a first scheduled MMR dose in children less than two years old without other conditions as per childhood immunization schedule, and second dose in two individuals less than six years old with sickle cell disease. Three individuals living with well controlled HIV, diabetes, and one who was pregnant at the time were offered MMR at appropriate timings due a history of incomplete MMR vaccination. Thirty-four ICTs were relatively immunocompromised due to being aged 60 and over. In this group, YFV decisions were made on a case-by-case basis. The pneumococcal vaccine and influenza vaccine status of the traveller was reviewed in those 65 and over. Non-immunocompromising co-morbidities were frequent in this group, with 26 out of 34 (76.5%) taking routine medications (e.g. statins, antihypertensives, inhaled salbutamol). Discussion specifically included management of co-morbidities during travel, travel insurance, and ensuring access to medical professional advice if relevant. Just 3.5% (n = 5) mildly ICTs were issued rescue antibiotic packs.