Malaria cases in China acquired through international travel, 2013-2022.

BACKGROUND: Despite the World Health Organisation certifying China malaria-free in 2021, the risk of local transmission caused by imported malaria cases remains a significant clinical and public health issue. It is necessary to present the changing trends of malaria in China and discuss the role of travel medicine services in consolidating malaria elimination. METHODS: This study systematically reviewed articles and reports related to human malaria from 2013 to 2022 published in international and Chinese databases. Data on malaria (i.e. number of cases, Plasmodium spp., diagnostic method, country of acquisition, provinces with high risk of re-introduction and transmission) were collected and synthesised, then summarised using descriptive statistics. RESULTS: Overall, 24 758 cases of malaria (>99.5% laboratory confirmed, > 99.2% imported, 0.5% fatal) were reported in China from 2013 to 2022, with a downward trend over the years (4128 cases in 2013 compared to 843 cases in 2022; χ2 trend p-value = 0.005). The last locally acquired case was reported in 2017. P. falciparum (65.5%) was the most common species identified, followed by P. vivax (20.9%) and P. ovale (10.0%). Two Pheidole knowlesi cases were also identified in 2014 and 2017 in returned travellers from Malaysia and Indonesia, respectively. The most common countries of malaria acquisition were Ghana, Angola, and Myanmar. P. vivax was mainly detected in returned travellers from Myanmar, while P. falciparum and P. ovale were detected in travellers from Sub-Saharan Africa. Imported cases were mainly reported in Yunnan, Jiangsu, Sichuan, Guangxi, Shandong, Zhejiang, and Henan provinces, where large numbers of Chinese people travel overseas for work. CONCLUSION: Returned travellers from malaria-endemic countries pose a significant risk of malaria re-introduction to China. Travel medicine should be strengthened to improve the capacity and accessibility of both pre- and post-travel services, including malaria prophylaxis and prompt diagnosis of illness in returned travellers.

Post-marketing surveillance of 10,392 herpes zoster vaccines doses in Australia.

BACKGROUND: Immunisation against herpes zoster is recommended for adults aged ≥ 50 years. Two vaccines, a live attenuated (ZVL, Zostavax®) and an adjuvant recombinant subunit (HZ/su, Shingrix®), are available in Australia. Immunisation guidelines are shifting their recommendations towards HZ/su because of higher efficacy in preventing herpes zoster and associated complications. However, there are limited post-marketing data comparing the safety profiles of these vaccines. METHODS: Data from SmartVax, an active surveillance system for monitoring adverse events following immunisation (AEFIs) utilised by > 450 clinics throughout Australia, were analysed. Data from patients aged ≥ 50 years, who received ZVL or HZ/su, from 1 June 2021 to 31 May 2022, at clinics that utilised SmartVax were included. The proportion of records where patients who reported any, local, and systemic AEFIs after receiving ZVL or HZ/su were compared using multivariable logistic regression models. RESULTS: Data from 10,392 immunisation records (n = 8341 ZVL; n = 2051 HZ/su) were included. The proportion of AEFIs reported was higher with HZ/su (41.9 % [any], 33.8 % [local], 25.2 % [systemic]) than with ZVL (8.7 % [any], 6.2 % [local], 3.5 % [systemic]). After controlling for demographic variables, HZ/su presented a 6-fold increase in the odds (OR 6.44; 95 %CI: 5.57-7.46) of a reported AEFI compared to ZVL. Only 59 (0.6 %) of vaccinations lead to medical attention being sought due to an AEFI. CONCLUSIONS: While rates of AEFIs was higher with HZ/su than ZVL, most AEFIs were mild and did not require medical attention. Our findings support the change in vaccine recommendations and the use of HZ/su in immunisation programs.

A systematic review and meta-analysis of sexually transmitted infections and blood-borne viruses in travellers.

BACKGROUND: Sexually transmitted infections (STIs) and blood-borne viruses (BBVs) impose a global health and economic burden. International travellers facilitate the spread of infectious diseases, including STIs. Hence, this review assessed the prevalence/proportionate morbidity of travellers with STIs and sexually transmitted BBVs and factors associated with the infection in this population. METHODS: PubMed, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase and Cochrane Library were searched from inception of the databases until November 2022. Published analytical observational studies reporting the prevalence/proportionate morbidity of travellers with STIs and factors associated with STIs by type of traveller [i.e. tourists, business travellers, students, visiting friends or relatives (VFRs), international truck drivers, backpackers, expatriates and men who have sex with men (MSM)] were included. The selection of articles, data extraction and risk of bias assessment were conducted by two independent reviewers. Meta-analyses were conducted for each STI by clinical presentation and type of traveller. RESULTS: Thirty-two studies (n = 387 731 travellers) were included; 19 evaluated the proportionate morbidity of STIs among symptomatic travellers, while 13 examined the prevalence of STIs in asymptomatic travellers. The highest proportionate morbidity was found among VFRs (syphilis, 1.67%; 95% CI: 1.03-2.81%), backpackers (Chlamydia trachomatis, 6.58%; 95% CI: 5.96-7.25%) and MSM (HIV [2.50%;95% CI: 0.44-12.88%], gonorrhoea [4.17%; 95% CI: 1.1.5-13.98%], lymphogranuloma venereum [4.17%;95% CI: 1.1.5-13.98%] and HAV [20.0%; 95% CI: 14.99-26.17%]). The highest prevalence of STIs among asymptomatic were found in MSM (HIV [25.94%; 95% CI: 22.21-30.05%] and HBV [24.90%; 95% CI: 21.23-28.96%]) and backpackers (C. trachomatis, 3.92%; 95% CI: 2.72-5.32%). Short duration of the trip (<1 month), not having pre-travel consultation, travelling to Southeast Asia and being unvaccinated for HBV were identified as risk factors for STIs. CONCLUSION: Strategies to prevent STIs and sexually transmitted BBVs should be discussed at pre-travel consultations, and recommendations should be prioritized in high-risk groups of travellers, such as backpackers, VFRs and MSMs. Additionally, healthcare providers should tailor recommendations for safe sex practices to individual travellers' unique needs.

Integrating sexual and reproductive health into pre-travel consultations.

BACKGROUND: Casual sex during travel is a major preventable factor in the global transmission of sexually transmissible infections (STI). Pre-travel consults present an excellent opportunity for practitioners to educate travellers about sexual and reproductive health (SRH) and safety. This scoping review aims to explore and understand the extent to which SRH is included in pre-travel consultations. METHODS: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, Medline and Web of Science were systematically searched for primary research articles exploring whether health care practitioners (HCP) included SRH in pre-travel consultations. Extracted findings were synthesized and presented in narrative form. RESULTS: Findings across 13 articles suggest HCPs infrequently broached SRH in pre-travel consultations with HCP discomfort, and lack of time and resources presented as key barriers. Urban practice settings, HCP experience, training in travel medicine and traveller characteristics such as sexual orientation were positively associated with discussions about SRH. SRH advice reported was general in nature, primarily focusing on safer sex, condoms or unspecified STI advice. Risk assessments based solely on age or stereotypes around sexual preferences led to key aspects of SRH care being missed for some (e.g. SRH was less likely to be discussed with older travellers). CONCLUSIONS: HCPs frequently miss opportunities to integrate SRH into pre-travel consultations. Strategies to promote HCP confidence and awareness present a promising means to boost the frequency and quality of SRH advice disseminated. Integrating culturally safe and responsive SRH history-taking and advice into pre-travel consultations may contribute to global reductions in STI transmission and promote traveller SRH well-being.

The provision of sexual and reproductive health information and services to travellers: an exploratory survey of Australian travel medicine clinicians.

BACKGROUND: International travel can increase the risk of exposure to infectious diseases including sexually transmissible infections (STI). Pre-travel medical consultation provides an opportunity for travel-related health risk assessments and advice. This study explored how travel medicine clinicians integrate sexual and reproductive health (SRH) services into clinical practice. METHODS: A convenience sample of travel medicine clinicians completed a cross-sectional survey online or via hard-copy disseminated at an annual national Australian travel medicine conference. RESULTS: Of the 67 respondents, most (n , 51; 76.1%) had a postgraduate qualification relevant to travel medicine and 55.2% (n , 37) had worked in travel medicine for over 10years. Only 22.4% (n , 15) reported conducting a SRH history/STI risk assessment for all travel patients. STI testing pre-departure was conducted on patient request (48, 71.6%), if symptomatic (32, 47.8%) or based on risk history (28, 41.8%). SRH information pre-departure was most frequently provided if prompted by patient questions (n , 42; 62.7%), or based on the patient's history (n , 37; 55.2%). Over half the sample (n , 40; 59.7%) expressed interest in further training in SRH. CONCLUSION: Providing and engaging with additional training may assist travel medicine clinicians to take a more proactive approach to SRH consultations and STI testing. Additional research is needed to explore models of care that will allow comprehensive SRH and STI services to be integrated into standard pre- and post-travel care.

Causes of death among international travellers in Peru, 2017 to 2021.

BACKGROUND: The wellbeing and safety of international tourists is a paramount concern for governments and stakeholders. Mortality among travellers and the causes of death serve as a significant metric of destination safety. We describe the epidemiology and causes of death among international travellers in Peru. METHODS: Data retrieved from the Peruvian government's deaths certificates registry included all non-residents who died between January 2017 and December 2021. We analysed the national incidence and causes of death among international travellers in Peru. Causes of death were classified into non-communicable diseases (NCD), communicable diseases and injuries. We classified fatalities according to the existence of preventive measures that could be provided during the travel medicine consultation to decrease the risk. RESULTS: We obtained records from 1514 deaths among international travellers (973 males, 64%). The incidence increased from 0.2 deaths per 10 000 travellers in 2017 to 9.9 in 2021. NCDs were the most common causes of death (n = 560, 37%), followed by communicable diseases (n = 487, 32%), and injuries (n = 321, 21%). Causes of death were unknown in 9.7% of the records. The leading causes of death in these categories were cancer, cardiovascular disease, COVID-19 and trauma. We found similar sex distribution of NCDs in travellers aged >50 years and higher rates of communicable diseases among males across all ages. Injury-associated deaths were significantly higher among males aged 18-29 years (P < 0.001) compared with other sex-age groups. We estimated that for 57.7% of deaths risk could have been decreased through pre-travel advice. CONCLUSION: Rates of deaths among travellers to Peru increased over time. Most deaths were due to NCDs, followed by communicable diseases and injuries. Pre-travel medical optimization and effective advice focused on age-sex and destination specific risks could reduce risk among travellers. Increased awareness among travel medicine practitioners and improvement of emergency medical response systems in Peru could decrease mortality.

A decision support tool for risk-benefit analysis of Japanese encephalitis vaccine in travellers.

BACKGROUND: During pre-travel consultations, clinicians and travellers face the challenge of weighing the risks verus benefits of Japanese encephalitis (JE) vaccination due to the high cost of the vaccine, low incidence in travellers (~1 in 1 million), but potentially severe consequences (~30% case-fatality rate). Personalised JE risk assessment based on the travellers' demographics and travel itinerary is challenging using standard risk matrices. We developed an interactive digital tool to estimate risks of JE infection and severe health outcomes under different scenarios to facilitate shared decision-making between clinicians and travellers. METHODS: A Bayesian network (conditional probability) model risk-benefit analysis of JE vaccine in travellers was developed. The model considers travellers' characteristics (age, sex, co-morbidities), itinerary (destination, departure date, duration, setting of planned activities) and vaccination status to estimate the risks of JE infection, the development of symptomatic disease (meningitis, encephalitis), clinical outcomes (hospital admission, chronic neurological complications, death) and adverse events following immunization. RESULTS: In low-risk travellers (e.g. to urban areas for <1 month), the risk of developing JE and dying is low (<1 per million) irrespective of the destination; thus, the potential impact of JE vaccination in reducing the risk of clinical outcomes is limited. In high-risk travellers (e.g. to rural areas in high JE incidence destinations for >2 months), the risk of developing symptomatic disease and mortality is estimated at 9.5 and 1.4 per million, respectively. JE vaccination in this group would significantly reduce the risk of symptomatic disease and mortality (by ~80%) to 1.9 and 0.3 per million, respectively. CONCLUSION: The JE tool may assist decision-making by travellers and clinicians and could increase JE vaccine uptake. The tool will be updated as additional evidence becomes available. Future work needs to evaluate the usability of the tool. The interactive, scenario-based, personalised JE vaccine risk-benefit tool is freely available on www.VaxiCal.com.

Immune response after rabies pre-exposure prophylaxis and a booster dose in Australian bat carers.

Periodic vaccination against rabies is essential for individuals at continuing risk of rabies exposure. There is limited evidence on long-term immunogenicity after a 3-dose intramuscular (3IM) pre-exposure prophylaxis (PrEP) and single IM booster dose, thus current guideline recommendations differ in the interval for serology tests following PrEP and boosters. This study investigated post-PrEP and post-booster persistence of antibodies in Australian bat carers. Bat carers who received 3IM PrEP/booster doses and had post-PrEP/booster serology test results were included. The proportion of antibody-negative (<0.5 EU/mL) individuals after PrEP/booster dose were examined. Three hundred and five participants (65.6% females, median age at PrEP 43.1 years) were included. The proportion who were antibody-negative varied depending on the time between 3IM PrEP and the serology test: 8.0% <1 year, 29.8% 1-2 years, 21.2% 2-3 years and 7.7% >3 years. Ninety-one participants receiving booster doses were further assessed. Only one participant was antibody-negative at >3 years after receiving one IM booster dose. Our findings support that a serology test should be performed 1 year after 3IM PrEP, followed by first booster if required. Rabies antibodies persist for many years after receiving the booster doses. The interval between subsequent serology tests and the first booster dose should be no longer than 3 years. Future studies are required to provide more insight into the most appropriate timing of subsequent boosters.

Immunogenicity of a single fractional intradermal dose of Japanese encephalitis live attenuated chimeric vaccine.

BACKGROUND: Japanese encephalitis (JE) is endemic in Asia and the western Pacific. Vaccination is recommended for travellers to endemic regions, but the high cost of the vaccine is a major barrier to uptake. METHODS: A quasi-experimental, pre-post intervention clinical trial without a control group was conducted to assess the immunogenicity and safety of intradermal (ID) JE vaccine. Healthy adults (18-45 years) received one dose of 0.1 mL (20% of standard dose) ID Imojev® (JE live attenuated chimeric vaccine, Sanofi-Aventis). Adverse events following immunization (AEFIs) were recorded 10 days post-vaccination. Blood samples were collected at baseline, 4 and 8 weeks post-vaccination. Neutralizing antibodies were measured using 50% plaque reduction neutralization test (PRNT50). Seroconversion was defined as PRNT50 titre ≥10. An in vitro study was also conducted to quantify the rate of decay of vaccine potency after reconstitution. RESULTS: In total, 51 participants (72.6% females, median age 31 years), all non-reactive to JE virus at baseline were enrolled. Mild and moderate AEFIs were reported by 19.6% of participants; none required medical attention or interfered with normal daily activities. All participants seroconverted at 4 weeks (GMT 249.3; 95%CI:192.8-322.5) and remained seropositive at 8 weeks (GMT 135.5; 95%CI:104.5-175.6). Vaccine potency declined at a rate of 0.14 log plaque-forming units/0.5 mL per hour. CONCLUSIONS: In healthy adults, a single 0.1 mL ID dose of Imojev was safe and immunogenic, at least in the short term. Reconstituted vials of Imojev vaccine may not retain their potency after 6 hours. Fractional JE ID vaccination could be a cheaper yet effective alternative for short-term travellers. Further studies need to investigate the immune response in a wider age range of individuals and the long-term immunogenicity of fractional JE ID vaccines. CLINICAL TRIALS REGISTRATION: ACTRN12621000024842.

The Emergence of Japanese Encephalitis in Australia and the Implications for a Vaccination Strategy.

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Until 2022, only six locally transmitted human JE cases had been reported in Australia; five in northern Queensland and one in the Northern Territory. Thus, JE was mainly considered to be a disease of travellers. On 4 March 2022, JE was declared a 'Communicable Disease Incident of National Significance' when a locally acquired human case was confirmed in southern Queensland. By 11 May 2022, 41 human JE cases had been notified in four states in Australia, in areas where JE has never been detected before. From this perspective, we discuss the potential reasons for the recent emergence of the JE virus in Australia in areas where JE has never been previously reported as well as the implications of and options for mass immunisation programs if the outbreak escalates in a JE virus-immunologically naïve population.

Persistence of antibodies, boostability, and interchangeability of Japanese encephalitis vaccines: A systematic review and dose-response meta-analysis.

BACKGROUND: The burden of Japanese encephalitis (JE) is substantial and is arguably one of the most serious viral encephalitic diseases with high case fatality and no specific treatment. JE vaccines are the only available mean to prevent the disease; however, the long-term persistence of antibodies, boostability, and interchangeability between different vaccine classes are not well understood. METHODS: To summarise the evidence, PubMed, Embase, and Cochrane CENTRAL were systematically searched from their inception to March 2021. Dose-response meta-analysis was utilised to synthesise the proportion of individuals who were seropositive over time after a primary vaccination course and a booster dose. Proportion meta-analysis was conducted to estimate the proportion of individuals who were seropositive as well as those who reported adverse events following a booster dose with a different vaccine class. RESULTS: Of 1053 publications retrieved, 27 studies with 4,558 participants were included. Of these, 11 studies assessed persistence of antibodies, 14 studies boostability, and 8 vaccine class interchangeability. The pooled seropositivity, 1-year after primary vaccination was 83.4% (95 %CI 78.2-89.5%) and remained stable for up to 5 years (82.7%; 95 %CI 76.1-89.4%). Rapid anamnestic response was observed 10 days post-booster dose, the proportion of individuals who were seropositive reached 96.9% (95 %CI 95.9-97.8%) and remained > 95% for up to 6 years. Inactivated mouse brain-derived vaccines followed by a booster dose of a different vaccine class was effective (i.e. seropositive 99%) and well tolerated. CONCLUSIONS: A booster dose after the primary vaccination is effective and further booster doses may be needed after 7 years. Inactivated mouse brain-derived vaccine followed by a booster with a newer vaccine class is effective and safe; although, there is a paucity of data related to newer classes of vaccines interchangeability.

Safety profile comparison of chimeric live attenuated and Vero cell-derived inactivated Japanese encephalitis vaccines through an active surveillance system in Australia.

Limited information is available about post-marketing safety of Japanese encephalitis (JE) vaccines. Using data from SmartVax, an active surveillance system for monitoring vaccine safety, adverse events following immunizations (AEFIs) were compared between the two JE vaccines available in Australia (a chimeric live attenuated vaccine [Imojev] and a Vero cell-derived inactivated vaccine [JEspect]). Data from 2756 patients (1855 Imojev and 901 JEspect) were included. Overall (7.0%), systemic (2.8%), and local (1.9%) AEFIs were uncommon. There were no significant differences in the odds of overall (OR = 1.27; 95%CI: 0.91-1.77), systemic (OR = 1.23; 95%CI: 0.74-2.06), or local (OR = 1.20; 95%CI: 0.65-2.22) AEFIs with Imojev compared to JEspect. There was an increase in odds of overall AEFI in patients aged <5 years (OR = 2.39; 95%CI: 1.10-5.19) compared to those aged >50 years. Both JE vaccines available in Australia are safe and well tolerated. Odds of AEFIs were age-dependent, young children should be carefully observed for AEFIs after vaccination.

Long-term persistence of antibodies and boostability after rabies intradermal pre-exposure prophylaxis.

BACKGROUND: Currently, there is limited data on long-term persistence of antibodies and boostability of intradermal (ID) rabies pre-exposure prophylaxis (PrEP) schedules. This study investigated travellers who received a primary ID PrEP schedule at least 5 years previously to determine the persistence of antibodies and subsequent antibody response after one 0.1-ml ID booster dose. METHODS: Adults (age ≥ 18 years) who had previously received ID PrEP at a specialist travel medicine clinic in Brisbane, Australia were included. At Day 0, blood was collected for serology and one dose of 0.1-ml ID rabies vaccine (Verorab®) was administered. At Day 7, serology was repeated. At Day 14, participants were given results and enquired if they experienced adverse events following immunization (AEFIs). Antibodies were measured using Platelia Rabies II ELISA; levels ≥0.5 EU/mL were considered antibody-positive. RESULTS: 158 participants were included [64.6% female, median age at enrolment 56.4 years, interquartile range (IQR) 42.4-65.2 years], and median time since the primary ID PrEP was 8.5 years (IQR 6.9-11.7 years). The majority of participants (82.3%) were antibody-positive at Day 0. The proportion of participants who were antibody-positive at Day 0 was higher among those who were younger at primary vaccination (87.0% if aged<50 years, 75.8% of aged ≥50 years). The proportion of participants who were antibody-positive declined as median time since primary vaccination increased, though the trend was not statistically significant (p-trend = 0.187). All except one participant (99.4%) were antibody-positive after one ID booster dose. AEFIs were reported by 42.4% of participants and were mainly mild. CONCLUSIONS: Rabies antibodies persist for many years after ID PrEP and can be rapidly boosted with a single ID dose. Future studies are needed to confirm that ID PrEP primes the immune system sufficiently so that boosters are not routinely needed, and only given in the event of a rabies-prone exposure.

Comparison of immunogenicity and safety of licensed Japanese encephalitis vaccines: A systematic review and network meta-analysis.

INTRODUCTION: Annually more than 100,000 Japanese encephalitis (JE) cases and 25,000 deaths worldwide are caused by JE virus infection. More than 15 JE vaccines are currently in use worldwide. It is unknown whether any of the vaccines is superior to the others in terms of immunogenicity and safety. METHODS: Four databases were systematically searched for randomised controlled trials that compared two or more types of JE vaccines. Vaccines were classified into four classes: inactivated mouse brain-derived (oldest class), inactivated Vero cell, live chimeric, and live attenuated. Network meta-analysis was used to generate mixed effect estimates against inactivated mouse brain-derived vaccines for seroconversion, and against placebo for adverse event (AE) and severe adverse event (SAE). RESULTS: 23 studies (38,496 participants) were included. All newer vaccine classes had better immunogenicity, the difference was statistically significant for inactivated Vero cell (OR = 2.98; 95 %CI: 1.02-8.65) and live chimeric (OR = 5.93; 95 %CI: 1.73-20.32) vaccines. Inactivated mouse-derived vaccines had the highest odds for AEs (OR = 2.27; 95 %CI: 1.59-3.23), the odds of AE of newer vaccines was not different to placebo. There was no difference in SAEs across vaccine classes. CONCLUSIONS: All newer JE vaccines have comparable safety profiles, live chimeric and inactivated Vero cell vaccines are the most immunogenic among the newer vaccine classes.

Efficacy of one-dose intramuscular rabies vaccine as pre-exposure prophylaxis in travellers.

BACKGROUND: Current guidelines for rabies pre-exposure prophylaxis (PrEP) recommend multiple vaccine doses. Travellers sometimes present for pre-travel consultation with insufficient time to complete standard PrEP schedules. We investigated the efficacy of one-dose intramuscular (IM) vaccine in priming the immune system (as PrEP) by measuring antibody response to simulated post-exposure prophylaxis (PEP). METHODS: A quasi-experimental pre-post intervention clinical trial was conducted at a specialist travel clinic in Australia. Adults (≥18 years) without a history of rabies vaccination were included. At Visit 1, seronegative status was confirmed and one dose of 0.5 ml IM rabies vaccine (Verorab®) administered. At Visit 2 (≥60 days after Visit 1), serology was repeated and a simulated PEP dose (0.5 ml IM) given on this day and again 3 days later (Visit 3). Serology was repeated at Visit 4 (7 days after Visit 2). RESULTS: A total of 94 antibody-negative participants were included (<50 years [n = 50]; ≥50 years [n = 44]). At Visit 2, 38.0 and 31.8% of participants aged <50 and ≥50 years were antibody-positive (≥0.5 EU/ml). At Visit 4, all participants were antibody-positive; 82.0 and 47.7% of participants aged <50 and ≥50 years had antibody levels >4 EU/ml, respectively. CONCLUSIONS: One-dose IM vaccine was effective as PrEP for priming the immune system in both age groups, resulting in rapid development of antibodies 7 days after commencing simulated PEP. If there is insufficient time to complete a standard PrEP schedule, one-dose IM could be considered as an alternative schedule for short trips, rather than not offering travellers any doses at all.Clinical trials registration: ACTRN12619000946112.