Novel chikungunya and dengue vaccines-travel medicine applications.

Recent epidemics of dengue and chikungunya have highlighted the urgent need for vaccines to reduce the risk of infection in travellers. Given challenges tracking chikungunya outbreaks in real-time and the widespread resurgence of dengue, broader indications for the use of the new chikungunya and dengue vaccines should be considered.

Powassan Virus Infections: A Systematic Review of Published Cases.

BACKGROUND: Powassan virus is an emerging neurotropic arbovirus transmitted by the tick Ixodes scapularis. This systematic review was conducted to aggregate data on its clinical manifestations, diagnostic findings, and complications. METHODS: PubMed was searched until August 2023 using the term "Powassan", to identify all published cases of Powassan virus infections, as per PRISMA guidelines. RESULTS: Among the 380 abstracts identified, 45 studies describing 84 cases (70 adult, 14 pediatric) were included. Cases were reported from the USA and Canada. Complications included paralysis in 44.1% of adult and 42.6% of pediatric cases, cognitive deficits in 33.3% of adult and 25% of pediatric cases, while the mortality rate was 19.1% and 7.1% in the adult and pediatric populations, respectively. Correlation analysis revealed an association between mortality and age (r = 0.264, p = 0.029), development of paralysis (r = 0.252, p = 0.041), or respiratory distress or failure (r = 0.328, p = 0.006). Factors associated with persistent neurological deficits were development of ataxia (r = 0.383, p = 0.006), paralysis (r = 0.278, p = 0.048), speech disorder (r = 0.319, p = 0.022), and cranial nerve involvement (r = 0.322, p = 0.017). Other significant correlations included those between speech disorders and ataxia (r = 0.526, p < 0.001), and between paralysis and respiratory distress or failure (r = 0.349, p = 0.003). CONCLUSION: Powassan virus infections have significant morbidity and mortality and should be suspected in cases of encephalitis and possible tick exposure. PROSPERO registration number: CRD42023395991.

Epidemiology and burden of dengue fever in the United States: a systematic review.

BACKGROUND: Dengue is currently a global concern. The range of dengue vectors is expanding with climate change, yet United States of America (USA) studies on dengue epidemiology and burden are limited. This systematic review sought to characterize the epidemiology and disease burden of dengue within the USA. METHODS: Studies evaluating travel-related and endemic dengue in US states and territories were identified and qualitatively summarized. Commentaries and studies on ex-US cases were excluded. MEDLINE, Embase, Cochrane Library, Latin American and Caribbean Center of Health Sciences Information, Centre for Reviews and Dissemination and Clinicaltrials.gov were searched through January 2022. RESULTS: 116 studies were included. In US states, dengue incidence was generally low, with spikes occurring in recent years in 2013-16 (0.17-0.31 cases/100,000) and peaking in 2019 (0.35 cases/100,000). Most cases (94%, n = 7895, 2010-21) were travel related. Dengue was more common in Puerto Rico (cumulative average: 200 cases/100,000, 1980-2015); in 2010-21, 99.9% of cases were locally acquired. There were <50 severe cases in US states (2010-17); fatal cases were even rarer. Severe cases in Puerto Rico peaked in 1998 (n = 173) and 2021 (n = 76). Besides lower income, risk factors in US states included having birds in residence, suggesting unspecified environmental characteristics favourable to dengue vectors. Commonly reported symptoms included fever, headache and rash; median disease duration was 3.5-11 days. Hospitalization rates increased following 2009 World Health Organization disease classification changes (pre-2009: 0-54%; post-2009: 14-75%); median length of stay was 2.7-8 days (Puerto Rico) and 2-3 days (US states). Hospitalization costs/case (2010 USD) were$14 350 (US states),$1764-$5497 (Puerto Rico) and$4207 (US Virgin Islands). In Puerto Rico, average days missed were 0.2-5.3 (work) and 2.5 (school). CONCLUSIONS: Though dengue risk is ongoing, treatments are limited, and dengue's economic burden is high. There is an urgent need for additional preventive and therapeutic interventions.

Influenza: seasonality and travel-related considerations.

RATIONALE FOR REVIEW: This review aims to summarize the transmission patterns of influenza, its seasonality in different parts of the globe, air travel- and cruise ship-related influenza infections and interventions to reduce transmission. KEY FINDINGS: The seasonality of influenza varies globally, with peak periods occurring mainly between October and April in the northern hemisphere (NH) and between April and October in the southern hemisphere (SH) in temperate climate zones. However, influenza seasonality is significantly more variable in the tropics. Influenza is one of the most common travel-related, vaccine-preventable diseases and can be contracted during travel, such as during a cruise or through air travel. Additionally, travellers can come into contact with people from regions with ongoing influenza transmission. Current influenza immunization schedules in the NH and SH leave individuals susceptible during their respective spring and summer months if they travel to the other hemisphere during that time. CONCLUSIONS/RECOMMENDATIONS: The differences in influenza seasonality between hemispheres have substantial implications for the effectiveness of influenza vaccination of travellers. Health care providers should be aware of influenza activity when patients report travel plans, and they should provide alerts and advise on prevention, diagnostic and treatment options. To mitigate the risk of travel-related influenza, interventions include antivirals for self-treatment (in combination with the use of rapid self-tests), extending the shelf life of influenza vaccines to enable immunization during the summer months for international travellers and allowing access to the influenza vaccine used in the opposite hemisphere as a travel-related vaccine. With the currently available vaccines, the most important preventive measure involves optimizing the seasonal influenza vaccination. It is also imperative that influenza is recognized as a travel-related illness among both travellers and health care professionals.

Travel-Related Diagnoses Among U.S. Nonmigrant Travelers or Migrants Presenting to U.S. GeoSentinel Sites - GeoSentinel Network, 2012-2021.

Problem/Condition: During 2012-2021, the volume of international travel reached record highs and lows. This period also was marked by the emergence or large outbreaks of multiple infectious diseases (e.g., Zika virus, yellow fever, and COVID-19). Over time, the growing ease and increased frequency of travel has resulted in the unprecedented global spread of infectious diseases. Detecting infectious diseases and other diagnoses among travelers can serve as sentinel surveillance for new or emerging pathogens and provide information to improve case identification, clinical management, and public health prevention and response. Reporting Period: 2012-2021. Description of System: Established in 1995, the GeoSentinel Network (GeoSentinel), a collaboration between CDC and the International Society of Travel Medicine, is a global, clinical-care-based surveillance and research network of travel and tropical medicine sites that monitors infectious diseases and other adverse health events that affect international travelers. GeoSentinel comprises 71 sites in 29 countries where clinicians diagnose illnesses and collect demographic, clinical, and travel-related information about diseases and illnesses acquired during travel using a standardized report form. Data are collected electronically via a secure CDC database, and daily reports are generated for assistance in detecting sentinel events (i.e., unusual patterns or clusters of disease). GeoSentinel sites collaborate to report disease or population-specific findings through retrospective database analyses and the collection of supplemental data to fill specific knowledge gaps. GeoSentinel also serves as a communications network by using internal notifications, ProMed alerts, and peer-reviewed publications to alert clinicians and public health professionals about global outbreaks and events that might affect travelers. This report summarizes data from 20 U.S. GeoSentinel sites and reports on the detection of three worldwide events that demonstrate GeoSentinel's notification capability. Results: During 2012-2021, data were collected by all GeoSentinel sites on approximately 200,000 patients who had approximately 244,000 confirmed or probable travel-related diagnoses. Twenty GeoSentinel sites from the United States contributed records during the 10-year surveillance period, submitting data on 18,336 patients, of which 17,389 lived in the United States and were evaluated by a clinician at a U.S. site after travel. Of those patients, 7,530 (43.3%) were recent migrants to the United States, and 9,859 (56.7%) were returning nonmigrant travelers.Among the recent migrants to the United States, the median age was 28.5 years (range = <19 years to 93 years); 47.3% were female, and 6.0% were U.S. citizens. A majority (89.8%) were seen as outpatients, and among 4,672 migrants with information available, 4,148 (88.8%) did not receive pretravel health information. Of 13,986 diagnoses among migrants, the most frequent were vitamin D deficiency (20.2%), Blastocystis (10.9%), and latent tuberculosis (10.3%). Malaria was diagnosed in 54 (<1%) migrants. Of the 26 migrants diagnosed with malaria for whom pretravel information was known, 88.5% did not receive pretravel health information. Before November 16, 2018, patients' reasons for travel, exposure country, and exposure region were not linked to an individual diagnosis. Thus, results of these data from January 1, 2012, to November 15, 2018 (early period), and from November 16, 2018, to December 31, 2021 (later period), are reported separately. During the early and later periods, the most frequent regions of exposure were Sub-Saharan Africa (22.7% and 26.2%, respectively), the Caribbean (21.3% and 8.4%, respectively), Central America (13.4% and 27.6%, respectively), and South East Asia (13.1% and 16.9%, respectively). Migrants with diagnosed malaria were most frequently exposed in Sub-Saharan Africa (89.3% and 100%, respectively).Among nonmigrant travelers returning to the United States, the median age was 37 years (range = <19 years to 96 years); 55.7% were female, 75.3% were born in the United States, and 89.4% were U.S. citizens. A majority (90.6%) were seen as outpatients, and of 8,967 nonmigrant travelers with available information, 5,878 (65.6%) did not receive pretravel health information. Of 11,987 diagnoses, the most frequent were related to the gastrointestinal system (5,173; 43.2%). The most frequent diagnoses among nonmigrant travelers were acute diarrhea (16.9%), viral syndrome (4.9%), and irritable bowel syndrome (4.1%).Malaria was diagnosed in 421 (3.5%) nonmigrant travelers. During the early (January 1, 2012, to November 15, 2018) and later (November 16, 2018, to December 31, 2021) periods, the most frequent reasons for travel among nonmigrant travelers were tourism (44.8% and 53.6%, respectively), travelers visiting friends and relatives (VFRs) (22.0% and 21.4%, respectively), business (13.4% and 12.3%, respectively), and missionary or humanitarian aid (13.1% and 6.2%, respectively). The most frequent regions of exposure for any diagnosis among nonmigrant travelers during the early and later period were Central America (19.2% and 17.3%, respectively), Sub-Saharan Africa (17.7% and 25.5%, respectively), the Caribbean (13.0% and 10.9%, respectively), and South East Asia (10.4% and 11.2%, respectively).Nonmigrant travelers who had malaria diagnosed were most frequently exposed in Sub-Saharan Africa (88.6% and 95.9% during the early and later period, respectively) and VFRs (70.3% and 57.9%, respectively). Among VFRs with malaria, a majority did not receive pretravel health information (70.2% and 83.3%, respectively) or take malaria chemoprophylaxis (88.3% and 100%, respectively). Interpretation: Among ill U.S. travelers evaluated at U.S. GeoSentinel sites after travel, the majority were nonmigrant travelers who most frequently received a gastrointestinal disease diagnosis, implying that persons from the United States traveling internationally might be exposed to contaminated food and water. Migrants most frequently received diagnoses of conditions such as vitamin D deficiency and latent tuberculosis, which might result from adverse circumstances before and during migration (e.g., malnutrition and food insecurity, limited access to adequate sanitation and hygiene, and crowded housing,). Malaria was diagnosed in both migrants and nonmigrant travelers, and only a limited number reported taking malaria chemoprophylaxis, which might be attributed to both barriers to acquiring pretravel health care (especially for VFRs) and lack of prevention practices (e.g., insect repellant use) during travel. The number of ill travelers evaluated by U.S. GeoSentinel sites after travel decreased in 2020 and 2021 compared with previous years because of the COVID-19 pandemic and associated travel restrictions. GeoSentinel detected limited cases of COVID-19 and did not detect any sentinel cases early in the pandemic because of the lack of global diagnostic testing capacity. Public Health Action: The findings in this report describe the scope of health-related conditions that migrants and returning nonmigrant travelers to the United States acquired, illustrating risk for acquiring illnesses during travel. In addition, certain travelers do not seek pretravel health care, even when traveling to areas in which high-risk, preventable diseases are endemic. Health care professionals can aid international travelers by providing evaluations and destination-specific advice.Health care professionals should both foster trust and enhance pretravel prevention messaging for VFRs, a group known to have a higher incidence of serious diseases after travel (e.g., malaria and enteric fever). Health care professionals should continue to advocate for medical care in underserved populations (e.g., VFRs and migrants) to prevent disease progression, reactivation, and potential spread to and within vulnerable populations. Because both travel and infectious diseases evolve, public health professionals should explore ways to enhance the detection of emerging diseases that might not be captured by current surveillance systems that are not site based.

Travel vaccines-priorities determined by incidence and impact.

BACKGROUND: Infectious disease epidemiology is continuously shifting. While travel has been disrupted by the COVID-19 pandemic and travel-related epidemiological research experienced a pause, further shifts in vaccine-preventable diseases (VPDs) relevant for travellers have occurred. METHODS: We conducted a literature search on the epidemiology of travel-related VPD and synthesized data for each disease with a focus on symptomatic cases and on the impact of the respective infection among travellers, considering the hospitalization rate, disease sequela and case fatality rate. We present new data and revised best estimates on the burden of VPD relevant for decisions on priorities in travel vaccines. RESULTS: COVID-19 has emerged to be a top travel-related risk and influenza remains high in the ranking with an estimated incidence at 1% per month of travel. Dengue is another commonly encountered infection among international travellers with estimated monthly incidence of 0.5-0.8% among non-immune exposed travellers; the hospitalized proportion was 10 and 22%, respectively, according to two recent publications. With recent yellow fever outbreaks particularly in Brazil, its estimated monthly incidence has risen to >0.1%. Meanwhile, improvements in hygiene and sanitation have led to some decrease in foodborne illnesses; however, hepatitis A monthly incidence remains substantial in most developing regions (0.001-0.01%) and typhoid remains particularly high in South Asia (>0.01%). Mpox, a newly emerged disease that demonstrated worldwide spread through mass gathering and travel, cannot be quantified regarding its travel-related risk. CONCLUSION: The data summarized may provide a tool for travel health professionals to prioritize preventive strategies for their clients against VPD. Updated assessments on incidence and impact are ever more important since new vaccines with travel indications (e.g. dengue) have been licensed or are undergoing regulatory review.

Impact, healthcare utilization and costs of travel-associated mosquito-borne diseases in international travellers: a prospective study.

BACKGROUND: International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus. METHODS: Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers' first contact with the health system in their country of residence. The patients were presented with a structured 52-question self-administered questionnaire after full recovery to collect information on patients' healthcare utilization and out-of-pocket costs both in the destination and home country, and about income and other financial losses due to the illness. RESULTS: A total of 134 patients participated in the study (malaria, 66; dengue, 51; chikungunya, 8; Zika virus, 9; all fully recovered; median age 40; range 18-72 years). Prior to travelling, 42% of patients reported procuring medical evacuation insurance. Across the four illnesses, only 7% of patients were hospitalized abroad compared with 61% at home. Similarly, 15% sought ambulatory services whilst abroad compared with 61% at home. The average direct out-of-pocket hospitalization cost in the destination country (USD $2236; range: $108-$5160) was higher than the direct out-of-pocket ambulatory cost in the destination country (USD $327; range: $0-$1560), the direct out-of-pocket hospitalization cost at home (USD $35; range: $0-$120) and the direct out-of-pocket ambulatory costs at home (US$45; range: $0-$192). Respondents with dengue or malaria lost a median of USD $570 (Interquartile range [IQR] 240-1140) and USD $240 (IQR 0-600), respectively, due to their illness, whilst those with chikungunya and Zika virus lost a median of USD $2400 (IQR 1200-3600) and USD $1500 (IQR 510-2625), respectively. CONCLUSION: Travellers often incur significant costs due to travel-acquired diseases. Further research into the economic impact of these diseases on travellers should be conducted.

Travel-associated melioidosis: a narrative review.

BACKGROUND: Melioidosis, caused by Burkholderia pseudomallei, may be considered a neglected tropical disease that remains underdiagnosed in many geographical areas. Travellers can act as the sentinels of disease activity, and data from imported cases may help complete the global map of melioidosis. METHODS: A literature search for imported melioidosis for the period 2016-22 was performed in PubMed and Google Scholar. RESULTS: In total, 137 reports of melioidosis associated with travel were identified. The majority were males (71%) and associated with exposure in Asia (77%) (mainly Thailand, 41%, and India, 9%). A minority acquired the infection in the Americas-Caribbean area (6%), Africa (5%) and Oceania (2%). The most frequent comorbidity was diabetes mellitus (25%) followed by underlying pulmonary, liver or renal disease (8, 5 and 3%, respectively). Alcohol/tobacco use were noted for seven and six patients, respectively (5%). Five patients (4%) had associated non-human immunodeficiency virus (HIV)-related immunosuppression, and three patients (2%) had HIV infection. One patient (0.8%) had concomitant coronavirus disease 19. A proportion (27%) had no underlying diseases. The most frequent clinical presentations included pneumonia (35%), sepsis (30%) and skin/soft tissue infections (14%). Most developed symptoms <1 week after return (55%), and 29% developed symptoms >12 weeks after. Ceftazidime and meropenem were the main treatments used during the intensive intravenous phase (52 and 41% of patients, respectively) and the majority (82%) received co-trimoxazole alone/combination, for the eradication phase. Most patients had a favourable outcome/survived (87%). The search also retrieved cases in imported animals or cases secondary to imported commercial products. CONCLUSIONS: As post-pandemic travel soars, health professionals should be aware of the possibility of imported melioidosis with its diverse presentations. Currently, no licensed vaccine is available, so prevention in travellers should focus on protective measures (avoiding contact with soil/stagnant water in endemic areas). Biological samples from suspected cases require processing in biosafety level 3 facilities.

Chikungunya: risks for travellers.

RATIONALE FOR REVIEW: Chikungunya outbreaks continue to occur, with changing epidemiology. Awareness about chikungunya is low both among the at-risk travellers and healthcare professionals, which can result in underdiagnosis and underreporting. This review aims to improve awareness among healthcare professionals regarding the risks of chikungunya for travellers. KEY FINDINGS: Chikungunya virus transmission to humans occurs mainly via daytime-active mosquitoes, Aedes aegypti and Aedes albopictus. The areas where these mosquitoes live is continuously expanding, partly due to climate changes. Chikungunya is characterized by an acute onset of fever with joint pain. These symptoms generally resolve within 1-3 weeks, but at least one-third of the patients suffer from debilitating rheumatologic symptoms for months to years. Large outbreaks in changing regions of the world since the turn of the 21st century (e.g. Caribbean, La Réunion; currently Brazil, India) have resulted in growing numbers of travellers importing chikungunya, mainly to Europe and North America. Viremic travellers with chikungunya infection have seeded chikungunya clusters (France, United States of America) and outbreaks (Italy in 2007 and 2017) in non-endemic countries where Ae. albopictus mosquitoes are present. Community preventive measures are important to prevent disease transmission by mosquitoes. Individual preventive options are limited to personal protection measures against mosquito bites, particularly the daytime-active mosquitos that transmit the chikungunya virus. Candidate vaccines are on the horizon and regulatory authorities will need to assess environmental and host risk factors for persistent sequelae, such as obesity, age (over 40 years) and history of arthritis or inflammatory rheumatologic disease to determine which populations should be targeted for these chikungunya vaccines. CONCLUSIONS/RECOMMENDATIONS: Travellers planning to visit destinations with active CHIKV circulation should be advised about the risk for chikungunya, prevention strategies, the disease manifestations, possible chronic rheumatologic sequelae and, if symptomatic, seek medical evaluation and report potential exposures.

Healthcare seeking during travel: an analysis by the GeoSentinel surveillance network of travel medicine providers.

BACKGROUND: International travellers may seek care abroad to address health problems that arise during their trip or plan healthcare outside their country of residence as medical tourists. METHODS: Data were collected on travellers evaluated at GeoSentinel Network sites who reported healthcare during travel. Both unplanned and planned healthcare were analysed, including the reason and nature of healthcare sought, characteristics of the treatment provided and outcomes. Travellers that presented for rabies post-exposure prophylaxis were described elsewhere and were excluded from detailed analysis. RESULTS: From May 2017 through June 2020, after excluding travellers obtaining rabies post-exposure prophylaxis (n= 415), 1093 travellers reported care for a medical or dental issue that was an unanticipated part of the travellers' planned itinerary (unplanned healthcare). Travellers who sought unplanned healthcare abroad had frequent diagnoses of acute diarrhoea, dengue, falciparum malaria and unspecified viral syndrome, and obtained care in 131 countries. Thirty-four (3%) reported subsequent deterioration and 230 (21%) reported no change in condition; a third (n = 405; 37%) had a pre-travel health encounter. Forty-one travellers had sufficient data on planned healthcare abroad for analysis. The most common destinations were the US, France, Dominican Republic, Belgium and Mexico. The top reasons for their planned healthcare abroad were unavailability of procedure at home (n = 9; 19%), expertise abroad (n = 9; 19%), lower cost (n = 8; 17%) and convenience (n = 7; 15%); a third (n = 13; 32%) reported cosmetic or surgical procedures. Early and late complications occurred in 14 (33%) and 4 (10%) travellers, respectively. Four travellers (10%) had a pre-travel health encounter. CONCLUSIONS: International travellers encounter health problems during travel that often could be prevented by pre-travel consultation. Travellers obtaining planned healthcare abroad can experience negative health consequences associated with treatments abroad, for which pre-travel consultations could provide advice and potentially help to prevent complications.

Chikungunya: An Emerging Public Health Concern.

Purpose of Review: The worldwide spread of chikungunya over the past two decades calls for greater knowledge and awareness of the virus, its route of transmission, methods of diagnosis, and the use of available treatment and prevention measures. Recent Findings: Chikungunya virus infection, an Aedes mosquito-borne febrile disease, has spread from Africa and Asia to Europe and the Americas and from the tropics and subtropics to temperate regions. International travel is a pivotal influence in the emergence of chikungunya as a global public health threat, as evidenced by a growing number of published reports on travel-related chikungunya infections. The striking features of chikungunya are arthralgia and arthritis, and the disease is often mistaken for dengue. Although mortality is low, morbidity can be profound and persistent. Current treatment for chikungunya is supportive; chikungunya vaccines and therapeutics are in development. Travelers planning to visit areas where the mosquito vectors are present should be advised on preventive measures. Summary: Chikungunya is an emerging disease in the Americas. Frequent travel, the presence of at least two competent mosquito species, and a largely naïve human population in the Western Hemisphere create a setting conducive to future outbreaks. Awareness of the disease and its manifestations is critical to effectively and safely manage and limit its impact. Vaccines in late-stage clinical trials offer a new pathway to prevention.

West Nile virus: another emerging arboviral risk for travelers?

Purpose of Review: West Nile virus (WNV) is an arbovirus transmitted by mosquitos of the genus Culex. Manifestations of WNV infection range from asymptomatic to devastating neuroinvasive disease leading to flaccid paralysis and death. This review examines WNV epidemiology and ecology, with an emphasis on travel-associated infection. Recent Findings: WNV is widespread, including North America and Europe, where its range has expanded in the past decade. Rising temperatures in temperate regions are predicted to lead to an increased abundance of Culex mosquitoes and an increase in their ability to transmit WNV. Although the epidemiologic patterns of WNV appear variable, its geographic distribution most certainly will continue to increase. Travelers are at risk for WNV infection and its complications. Literature review identified 39 cases of documented travel-related WNV disease, the majority of which resulted in adverse outcomes, such as neuroinvasive disease, prolonged recovery period, or death. Summary: The prediction of WNV risk is challenging due to the complex interactions of vector, pathogen, host, and environment. Travelers planning to visit endemic areas should be advised regarding WNV risk and mosquito bite prevention. Evaluation of ill travelers with compatible symptoms should consider the diagnosis of WNV for those visiting in endemic areas as well as for those returning from destinations with known WNV circulation.

Travel in the Time of COVID: A Review of International Travel Health in a Global Pandemic.

Purpose of Review: This review critically considers the impact of the COVID-19 pandemic on global travel and the practice of travel medicine, highlights key innovations that have facilitated the resumption of travel, and anticipates how travel medicine providers should prepare for the future of international travel. Recent Findings: Since asymptomatic transmission of the virus was first recognized in March 2020, extensive efforts have been made to characterize the pattern and dynamics of SARS-CoV-2 transmission aboard commercial aircraft, cruise ships, rail and bus transport, and in mass gatherings and quarantine facilities. Despite the negative impact of further waves of COVID-19 driven by the more transmissible Omicron variant, rapid increases of international tourist arrivals are occurring and modeling anticipates further growth. Mitigation of spread requires an integrated approach that combines masking, physical distancing, improving ventilation, testing, and quarantine. Vaccines and therapeutics have played a significant role in reopening society and accelerating the resumption of travel and further therapeutic innovation is likely. Summary: COVID-19 is likely to persist as an endemic infection, and surveillance will assume an even more important role. The pandemic has provided an impetus to advance technology for telemedicine, to adopt mobile devices and GPS in contact tracing, and to apply digital applications in research. The future of travel medicine should continue to harness these novel platforms in the clinical, research, and educational arenas.

Treatment strategies for nitroimidazole-refractory giardiasis: a systematic review.

RATIONALE FOR REVIEW: Giardiasis is one of the most common human protozoal infections worldwide. First-line therapy of giardiasis includes nitroimidazole antibiotics. However, treatment failure with nitroimidazoles is increasingly reported, with up to 45% of patients not responding to initial treatment. There is no clear consensus on the approach to the management of nitroimidazole-refractory giardiasis. This systematic review aims to summarize the literature on pharmacotherapy for nitroimidazole-refractory giardiasis. METHODS: We conducted a systematic review of the literature to determine the optimal management strategies for nitroimidazole-refractory giardiasis. We searched Pubmed/MEDLINE, Embase and Cochrane library using the following search terms 'Giardia' AND 'treatment failure' OR 'refractory giardia' OR 'resistant giardia' with date limits of 1 January 1970 to 30 June 2021. We included all reports on humans, which described clinical outcomes of individuals with treatment refractory giardiasis, including case series and case reports. A descriptive synthesis of the data was conducted with pooling of data for interventions. KEY FINDINGS: Included in this review were five prospective studies, three retrospective studies, seven case series and nine case reports. Across these reports, a wide heterogeneity of treatment regimens was employed, including retreatment with an alternative nitroimidazole, combination therapy with a nitroimidazole and another agent and monotherapy with non-nitroimidazole regimens, including quinacrine, paromomycin and nitazoxanide. Retreatment with a nitroimidazole was not an effective therapy for refractory giardiasis. However, treatment with a nitroimidazole in combination with albendazole had a cure rate of 66.9%. In the included studies, quinacrine monotherapy was administered to a total of 179 patients, with a clinical cure rate of 88.8%. Overall, quinacrine was fairly well tolerated. CONCLUSIONS: Reports on the treatment of nitroimidazole-refractory giardiasis demonstrate a heterogeneous approach to treatment. Of these, quinacrine appeared to be highly effective, though more data on its safety are needed.

Multidrug-resistant tuberculosis imported into low-incidence countries-a GeoSentinel analysis, 2008-2020.

BACKGROUND: Early detection of imported multidrug-resistant tuberculosis (MDR-TB) is crucial, but knowledge gaps remain about migration- and travel-associated MDR-TB epidemiology. The aim was to describe epidemiologic characteristics among international travellers and migrants with MDR-TB. METHODS: Clinician-determined and microbiologically confirmed MDR-TB diagnoses deemed to be related to travel or migration were extracted from GeoSentinel, a global surveillance network of travel and tropical medicine clinics, from January 2008 through December 2020. MDR-TB was defined as resistance to both isoniazid and rifampicin. Additional resistance to either a fluoroquinolone or a second-line injectable drug was categorized as pre-extensively drug-resistant (pre-XDR) TB, and as extensively drug-resistant (XDR) TB when resistance was detected for both. Sub-analyses were performed based on degree of resistance and country of origin. RESULTS: Of 201 patients, 136 had MDR-TB (67.7%), 25 had XDR-TB (12.4%), 23 had pre-XDR TB (11.4%) and 17 had unspecified MDR- or XDR-TB (8.5%); 196 (97.5%) were immigrants, of which 92 (45.8%) originated from the former Soviet Union. The median interval from arrival to presentation was 154 days (interquartile range [IQR]: 10-751 days); 34.3% of patients presented within 1 month after immigration, 30.9% between 1 and 12 months and 34.9% after ≥1 year. Pre-XDR- and XDR-TB patients from the former Soviet Union other than Georgia presented earlier than those with MDR-TB (26 days [IQR: 8-522] vs. 369 days [IQR: 84-827]), while patients from Georgia presented very early, irrespective of the level of resistance (8 days [IQR: 2-18] vs. 2 days [IQR: 1-17]). CONCLUSIONS: MDR-TB is uncommon in traditional travellers. Purposeful medical migration may partly explain differences in time to presentation among different groups. Public health resources are needed to better understand factors contributing to cross-border MDR-TB spread and to develop strategies to optimize care of TB-infected patients in their home countries before migration.