COVID-19 impact on EuroTravNet infectious diseases sentinel surveillance in Europe.

BACKGROUND: The COVID-19 pandemic resulted in a sharp decline of post-travel patient encounters at the European sentinel surveillance network (EuroTravNet) of travellers' health. We report on the impact of COVID-19 on travel-related infectious diseases as recorded by EuroTravNet clinics. METHODS: Travelers who presented between January 1, 2019 and September 30, 2021 were included. Comparisons were made between the pre-pandemic period (14 months from January 1, 2019 to February 29, 2020); and the pandemic period (19 months from March 1, 2020 to September 30, 2021). RESULTS: Of the 15,124 visits to the network during the 33-month observation period, 10,941 (72%) were during the pre-pandemic period, and 4183 (28%) during the pandemic period. Average monthly visits declined from 782/month (pre-COVID-19 era) to 220/month (COVID-19 pandemic era). Among non-migrants, the top-10 countries of exposure changed after onset of the COVID-19 pandemic; destinations such as Italy and Austria, where COVID-19 exposure peaked in the first months, replaced typical travel destinations in Asia (Thailand, Indonesia, India). There was a small decline in migrant patients reported, with little change in the top countries of exposure (Bolivia, Mali). The three top diagnoses with the largest overall decreases in relative frequency were acute gastroenteritis (-5.3%), rabies post-exposure prophylaxis (-2.8%), and dengue (-2.6%). Apart from COVID-19 (which rose from 0.1% to 12.7%), the three top diagnoses with the largest overall relative frequency increase were schistosomiasis (+4.9%), strongyloidiasis (+2.7%), and latent tuberculosis (+2.4%). CONCLUSIONS: A marked COVID-19 pandemic-induced decline in global travel activities is reflected in reduced travel-related infectious diseases sentinel surveillance reporting.

Travel-related infections presenting in Europe: A 20-year analysis of EuroTravNet surveillance data.

BACKGROUND: Disease epidemiology of (re-)emerging infectious diseases is changing rapidly, rendering surveillance of travel-associated illness important. METHODS: We evaluated travel-related illness encountered at EuroTravNet clinics, the European surveillance sub-network of GeoSentinel, between March 1, 1998 and March 31, 2018. FINDINGS: 103,739 ill travellers were evaluated, including 11,239 (10.8%) migrants, 89,620 (86.4%) patients seen post-travel, and 2,880 (2.8%) during and after travel. Despite increasing numbers of patient encounters over 20 years, the regions of exposure by year of clinic visits have remained stable. In 5-year increments, greater proportions of patients were migrants or visiting friends and relatives (VFR); business travel-associated illness remained stable; tourism-related illness decreased. Falciparum malaria was amongst the most-frequently diagnosed illnesses with 5,254 cases (5.1% of all patients) and the most-frequent cause of death (risk ratio versus all other illnesses 2.5:1). Animal exposures requiring rabies post-exposure prophylaxis increased from 0.7% (1998-2002) to 3.6% (2013-2018). The proportion of patients with seasonal influenza increased from zero in 1998-2002 to 0.9% in 2013-2018. There were 44 cases of viral haemorrhagic fever, most during the past five years. Arboviral infection numbers increased significantly as did the range of presenting arboviral diseases, dengue and chikungunya diagnoses increased by 2.6% and 1%, respectively. INTERPRETATION: Travel medicine must adapt to serve the changing profile of travellers, with an increase in migrants and persons visiting relatives and friends and the strong emergence of vector-borne diseases, with potential for further local transmission in Europe. FUNDING: This project was supported by a cooperative agreement (U50CK00189) between the Centers for Disease Control and Prevention to the International Society of Travel Medicine (ISTM) and funding from the ISTM and the Public Health Agency of Canada.

Travel-associated infection presenting in Europe (2008-12): an analysis of EuroTravNet longitudinal, surveillance data, and evaluation of the effect of the pre-travel consultation.

BACKGROUND: Travel is important in the acquisition and dissemination of infection. We aimed to assess European surveillance data for travel-related illness to profile imported infections, track trends, identify risk groups, and assess the usefulness of pre-travel advice. METHODS: We analysed travel-associated morbidity in ill travellers presenting at EuroTravNet sites during the 5-year period of 2008-12. We calculated proportionate morbidity per 1000 ill travellers and made comparisons over time and between subgroups. We did 5-year trend analyses (2008-12) by testing differences in proportions between subgroups using Pearson's χ(2) test. We assessed the effect of the pre-travel consultation on infection acquisition and outcome by use of proportionate morbidity ratios. FINDINGS: The top diagnoses in 32 136 patients, ranked by proportionate morbidity, were malaria and acute diarrhoea, both with high proportionate morbidity (>60). Dengue, giardiasis, and insect bites had high proportionate morbidity (>30) as well. 5-year analyses showed increases in vector borne infections with significant peaks in 2010; examples were increased Plasmodium falciparum malaria (χ(2)=37·57, p<0·001); increased dengue fever (χ(2)=135·9, p<0·001); and a widening geographic range of acquisition of chikungunya fever. The proportionate morbidity of dengue increased from 22 in 2008 to 36 in 2012. Five dengue cases acquired in Europe contributed to this increase. Dermatological diagnoses increased from 851 in 2008 to 1102 in 2012, especially insect bites and animal-related injuries. Respiratory infection trends were dominated by the influenza H1N1 pandemic in 2009. Illness acquired in Europe accounted for 1794 (6%) of all 32 136 cases-mainly, gastrointestinal (634) and respiratory (357) infections. Migration within Europe was associated with more serious infection such as hepatitis C, tuberculosis, hepatitis B, and HIV/AIDS. Pre-travel consultation was associated with significantly lower proportionate morbidity ratios for P falciparum malaria and also for acute hepatitis and HIV/AIDS. INTERPRETATION: The pattern of travel-related infections presenting in Europe is complex. Trend analyses can inform on emerging infection threats. Pre-travel consultation is associated with reduced malaria proportionate morbidity ratios and less severe illness. These findings support the importance and effectiveness of pre-travel advice on malaria prevention, but cast doubt on the effectiveness of current strategies to prevent travel-related diarrhoea. FUNDING: European Centre for Disease Prevention and Control, University Hospital Institute Méditerranée Infection, US Centers for Disease Control and Prevention, and the International Society of Travel Medicine.

Travel-related infection in European travelers, EuroTravNet 2011.

BACKGROUND: Limited data exist on infectious diseases imported to various locations in Europe, particularly after travel within the continent. METHODS: To investigate travel-related disease relevant to Europe that is potentially preventable through pre-travel intervention, we analyzed the EuroTravNet database of 5,965 ill travelers reported by 16 centers in "Western" Europe in 2011. RESULTS: There were 54 cases of vaccine-preventable disease, mostly hepatitis A (n = 16), typhoid fever (n = 11), and measles (n = 8); 6 cases (including 3 measles cases) were associated with travel within "Western" Europe. Malaria was the most commonly diagnosed infection (n = 482, 8.1% of all travel-related morbidity). Among patients with malaria, the military most commonly received pre-travel advice (95%), followed by travelers for missionary, volunteer, research, or aid work (81%) but travelers visiting friends and relatives (VFRs) were least likely to receive pre-travel advice (21%). The vast majority (96%) of malaria patients were resident in "Western" Europe, but over half (56%) were born elsewhere. Other significant causes of morbidity, which could be reduced through advice and behavioral change, include Giardia (n = 221, 3.7%), dengue (n = 146, 2.4%), and schistosomiasis (n = 131, 2.2%). Of 206 (3.5%) travelers with exposure in "Western" Europe, 75% were tourists; the highest burden of disease was acute gastrointestinal infection (35% cases). Travel from "Eastern" Europe (n = 132, 2.2%) was largely associated with migration-related travel (53%); among chronic infectious diseases, tuberculosis was frequently diagnosed (n = 20). Travelers VFRs contributed the largest group of malaria patients (46%), but also had the lowest documented rate of pre-travel health advice in this subset (20%). Overall, 44% of nonimmigrant ill travelers did not receive pre-travel advice. CONCLUSION: There is a burden of infectious diseases in travelers attending European health centers that is potentially preventable through comprehensive pre-travel advice, chemoprophylaxis, and vaccination. Targeted interventions for high-risk groups such as travelers VFRs and migration-associated travelers are of particular importance.

Spectrum of illness in international migrants seen at GeoSentinel clinics in 1997-2009, part 1: US-bound migrants evaluated by comprehensive protocol-based health assessment.

BACKGROUND: Many nations are struggling to develop structured systems and guidelines to optimize the health of new arrivals, but there is currently no international consensus about the best approach. METHODS: Data on 7792 migrants who crossed international borders for the purpose of resettlement and underwent a protocol-based health assessment were collected from the GeoSentinel Surveillance network. Demographic and health characteristics of a subgroup of these migrants seen at 2 US-based GeoSentinel clinics for protocol-based health assessments are described. RESULTS: There was significant variation over time in screened migrant populations and in their demographic characteristics. Significant diagnoses identified in all migrant groups included latent tuberculosis, found in 43% of migrants, eosinophilia in 15%, and hepatitis B infection in 6%. Variation by region occurred for select diagnoses such as parasitic infections. Notably absent were infectious tuberculosis, soil-transmitted helminths, and malaria. Although some conditions would be unfamiliar to clinicians in receiving countries, universal health problems such as dental caries, anemia, ophthalmologic conditions, and hypertension were found in 32%, 11%, 10%, and 5%, respectively, of screened migrants. CONCLUSIONS: Data from postarrival health assessments can inform clinicians about screening tests to perform in new immigrants and help communities prepare for health problems expected in specific migrant populations. These data support recommendations developed in some countries to screen all newly arriving migrants for some specific diseases (such as tuberculosis) and can be used to help in the process of developing additional screening recommendations that might be applied broadly or focused on specific at-risk populations.

Spectrum of illness in international migrants seen at GeoSentinel clinics in 1997-2009, part 2: migrants resettled internationally and evaluated for specific health concerns.

BACKGROUND: Increasing international migration may challenge healthcare providers unfamiliar with acute and long latency infections and diseases common in this population. This study defines health conditions encountered in a large heterogenous group of migrants. METHODS: Migrants seen at GeoSentinel clinics for any reason, other than those seen at clinics only providing comprehensive protocol-based health screening soon after arrival, were included. Proportionate morbidity for syndromes and diagnoses by country or region of origin were determined and compared. RESULTS: A total of 7629 migrants from 153 countries were seen at 41 GeoSentinel clinics in 19 countries. Most (59%) were adults aged 19-39 years; 11% were children. Most (58%) were seen >1 year after arrival; 27% were seen after >5 years. The most common diagnoses were latent tuberculosis (22%), viral hepatitis (17%), active tuberculosis (10%), human immunodeficiency virus (HIV)/AIDS (7%), malaria (7%), schistosomiasis (6%), and strongyloidiasis (5%); 5% were reported healthy. Twenty percent were hospitalized (24% for active tuberculosis and 21% for febrile illness [83% due to malaria]), and 13 died. Tuberculosis diagnoses and HIV/AIDS were reported from all regions, strongyloidiasis from most regions, and chronic hepatitis B virus (HBV) particularly in Asian immigrants. Regional diagnoses included schistosomiasis (Africa) and Chagas disease (Americas). CONCLUSIONS: Eliciting a migration history is important at every encounter; migrant patients may have acute illness or chronic conditions related to exposure in their country of origin. Early detection and treatment, particularly for diagnoses related to tuberculosis, HBV, Strongyloides, and schistosomiasis, may improve outcomes. Policy makers should consider expansion of refugee screening programs to include all migrants.

Travel-associated sexually transmitted infections: an observational cross-sectional study of the GeoSentinel surveillance database.

BACKGROUND: Travel is thought to be a risk factor for the acquisition of sexually transmitted infections (STIs), but no multicentre analyses have been done. We aimed to describe the range of diseases and the demographic and geographical factors associated with the acquisition of travel-related STIs through analysis of the data gathered by GeoSentinel travel medicine clinics worldwide. METHODS: We gathered data from ill travellers visiting GeoSentinel clinics worldwide between June 1, 1996, and Nov 30, 2010, and analysed them to identify STIs in three clinical settings: after travel, during travel, or immigration travel. We calculated proportionate morbidity for each of the three traveller groups and did logistic regression to assess the association between STIs and demographic, geographical, and travel variables. FINDINGS: Our final analysis was of 112 180 ill travellers-64 335 patients seen after travel, 38 287 patients seen during travel, and 9558 immigrant patients. 974 patients (0·9%) had diagnoses of STIs, and 1001 STIs were diagnosed. The proportionate STI morbidities were 6·6, 10·2, and 16·8 per 1000 travellers in the three groups, respectively. STIs varied substantially according to the traveller category. The most common STI diagnoses were non-gonococcal or unspecified urethritis (30·2%) and acute HIV infection (27·6%) in patients seen after travel; non-gonococcal or unspecified urethritis (21·1%), epididymitis (15·2%), and cervicitis (12·3%) in patients seen during travel; and syphilis in immigrant travellers (67·8%). In ill travellers seen after travel, significant associations were noted between diagnosis of STIs and male sex, travelling to visit friends or relatives, travel duration of less than 1 month, and not having pretravel health consultations. INTERPRETATION: The range of STIs varies substantially according to traveller category. STI preventive strategies should be particularly targeted at men and travellers visiting friends or relatives. Our data suggest target groups for pretravel interventions and should assist in post-travel screening and decision making. FUNDING: US Centers for Disease Control and Prevention, and International Society of Travel Medicine.

Travel and migration associated infectious diseases morbidity in Europe, 2008.

BACKGROUND: Europeans represent the majority of international travellers and clinicians encountering returned patients have an essential role in recognizing, and communicating travel-associated public health risks. METHODS: To investigate the morbidity of travel associated infectious diseases in European travellers, we analysed diagnoses with demographic, clinical and travel-related predictors of disease, in 6957 ill returned travellers who presented in 2008 to EuroTravNet centres with a presumed travel associated condition. RESULTS: Gastro-intestinal (GI) diseases accounted for 33% of illnesses, followed by febrile systemic illnesses (20%), dermatological conditions (12%) and respiratory illnesses (8%). There were 3 deaths recorded; a sepsis caused by Escherichia coli pyelonephritis, a dengue shock syndrome and a Plasmodium falciparum malaria.GI conditions included bacterial acute diarrhea (6.9%), as well as giardiasis and amebasis (2.3%). Among febrile systemic illnesses with identified pathogens, malaria (5.4%) accounted for most cases followed by dengue (1.9%) and others including chikungunya, rickettsial diseases, leptospirosis, brucellosis, Epstein Barr virus infections, tick-borne encephalitis (TBE) and viral hepatitis. Dermatological conditions were dominated by bacterial infections, arthropod bites, cutaneous larva migrans and animal bites requiring rabies post-exposure prophylaxis and also leishmaniasis, myasis, tungiasis and one case of leprosy. Respiratory illness included 112 cases of tuberculosis including cases of multi-drug resistant or extensively drug resistant tuberculosis, 104 cases of influenza like illness, and 5 cases of Legionnaires disease. Sexually transmitted infections (STI) accounted for 0.6% of total diagnoses and included HIV infection and syphilis. A total of 165 cases of potentially vaccine preventable diseases were reported. Purpose of travel and destination specific risk factors was identified for several diagnoses such as Chagas disease in immigrant travellers from South America and P. falciparum malaria in immigrants from sub-Saharan Africa. Travel within Europe was also associated with health risks with distinctive profiles for Eastern and Western Europe. CONCLUSIONS: In 2008, a broad spectrum of travel associated diseases were diagnosed at EuroTravNet core sites. Diagnoses varied according to regions visited by ill travellers. The spectrum of travel associated morbidity also shows that there is a need to dispel the misconception that travel, close to home, in Europe, is without significant health risk.

Characteristics of schistosomiasis in travelers reported to the GeoSentinel Surveillance Network 1997-2008.

Among ill returned travelers to Schistosoma-endemic areas reported to the GeoSentinel Surveillance Network over a decade 410 schistosomiasis diagnoses were identified: 102 Schistosoma mansoni, 88 S. haematobium, 7 S. japonicum, and 213 Schistosoma unknown human species. A total of 83% were acquired in Africa. Unlike previous large case series, individuals born in endemic areas were excluded. Controlling for age and sex, those traveling for missionary or volunteer work, or as expatriates were more likely to be diagnosed with schistosomiasis. Sixty-three percent of those with schistosomiasis presented within six months of travel. Those seen early more often presented with fever and respiratory symptoms compared with those who presented later. One-third of patients with schistosomiasis were asymptomatic at diagnosis. Half of those examined for schistosomiasis were diagnosed with infection. Screening for schistosomiasis should be encouraged for all potentially exposed travelers and especially for missionaries, volunteers, and expatriates.

Gastrointestinal infection among international travelers globally.

BACKGROUND: Data on relative rates of acquisition of gastrointestinal infections by travelers are incomplete. The objective of this study was to analyze infections associated with oral ingestion of pathogens in international travelers in relation to place of exposure. METHODS: We performed a multicenter, retrospective observational analysis of 6,086 travelers ill enough with any gastrointestinal infection to seek medical care at a GeoSentinel clinic after completion of travel during 2000 to 2005. We determined regional and country-specific reporting rate ratios (RRRs) in comparison to risk in northern and western Europe. RESULTS: Travel to sub-Saharan Africa (RRR = 282), South America (RRR = 203), and South Asia (RRR = 890) was associated with the greatest rate of gastrointestinal infections. RRRs were moderate (25-142) for travel to Oceania, the Middle East, North Africa, Central America, the Caribbean, and Southeast Asia. RRRs were least (<28) following travel to southern, central, and eastern Europe; North America; Northeast Asia; and Australasia. Income level of the country visited was inversely proportional to the RRR for gastrointestinal infection. For bacterial and parasitic infections examined separately, the regions group in the same way. RRRs could be estimated for 28 individual countries and together with regional data were used to derive a global RRR map for travel-related gastrointestinal infection. CONCLUSIONS: This analysis of morbidity associated with oral ingestion of pathogens abroad determines which parts of the world currently are high-risk destinations.

Seasonality, annual trends, and characteristics of dengue among ill returned travelers, 1997-2006.

We examined seasonality and annual trends for dengue cases among 522 returned travelers reported to the international GeoSentinel Surveillance Network. Dengue cases showed region-specific peaks for Southeast Asia (June, September), South Central Asia (October), South America (March), and the Caribbean (August, October). Travel-related dengue exhibited annual oscillations with several epidemics occurring during the study period. In Southeast Asia, annual proportionate morbidity increased from 50 dengue cases per 1,000 ill returned travelers in nonepidemic years to an average of 159 cases per 1,000 travelers during epidemic years. Dengue can thus be added to the list of diseases for which pretravel advice should include information on relative risk according to season. Also, dengue cases detected at atypical times in sentinel travelers may inform the international community of the onset of epidemic activity in specific areas.

Dermatologic conditions of the ill returned traveler: an analysis from the GeoSentinel Surveillance Network.

BACKGROUND: Skin disorders are common in travelers. Knowledge of the relative frequency of post-travel-related skin disorders, including their geographic and demographic risk factors, will allow for effective pre-travel counseling, as well as improved post-travel diagnosis and therapeutic intervention. METHODS: We performed a retrospective study using anonymous patient demographic, clinical, and travel-related data from the GeoSentinel Surveillance Network clinics from January 1997 through February 2006. The characteristics of these travelers and their itineraries were analyzed using SAS 9.0 statistical software. RESULTS: A skin-related diagnosis was reported for 4594 patients (18% of all patients seen in a GeoSentinel clinic after travel). The most common skin-related diagnoses were cutaneous larva migrans (CLM), insect bites including superinfected bites, skin abscess, and allergic reaction (38% of all diagnoses). Arthropod-related skin diseases accounted for 31% of all skin diagnoses. Ill travelers who visited countries in the Caribbean experienced the highest proportionate morbidity due to dermatologic conditions. Pediatric travelers had significantly more dog bites and CLM and fewer insect bites compared with their adult counterparts; geriatric travelers had proportionately more spotted fever and cellulitis. CONCLUSIONS: Clinicians seeing patients post-travel should be alert to classic travel-related skin diseases such as CLM as well as more mundane entities such as pyodermas and allergic reactions. To prevent and manage skin-related morbidity during travel, international travelers should avoid direct contact with sand, soil, and animals and carry a travel kit including insect repellent, topical antifungals, and corticosteroids and, in the case of extended and/or remote travel, an oral antibiotic with ample coverage for pyogenic organisms.

Fever in returned travelers: results from the GeoSentinel Surveillance Network.

BACKGROUND: Fever is a marker of potentially serious illness in returned travelers. Information about causes of fever, organized by geographic area and traveler characteristics, can facilitate timely, appropriate treatment and preventive measures. METHODS: Using a large, multicenter database, we assessed how frequently fever is cited as a chief reason for seeking medical care among ill returned travelers. We defined the causes of fever by place of exposure and traveler characteristics. RESULTS: Of 24,920 returned travelers seen at a GeoSentinel clinic from March 1997 through March 2006, 6957 (28%) cited fever as a chief reason for seeking care. Of patients with fever, 26% were hospitalized (compared with 3% who did not have fever); 35% had a febrile systemic illness, 15% had a febrile diarrheal disease, and 14% had fever and a respiratory illness. Malaria was the most common specific etiologic diagnosis, found in 21% of ill returned travelers with fever. Causes of fever varied by region visited and by time of presentation after travel. Ill travelers who returned from sub-Saharan Africa, south-central Asia, and Latin America whose reason for travel was visiting friends and relatives were more likely to experience fever than any other group. More than 17% of travelers with fever had a vaccine-preventable infection or falciparum malaria, which is preventable with chemoprophylaxis. Malaria accounted for 33% of the 12 deaths among febrile travelers. CONCLUSIONS: Fever is common in ill returned travelers and often results in hospitalization. The time of presentation after travel provides important clues toward establishing a diagnosis. Preventing and promptly treating malaria, providing appropriate vaccines, and identifying ways to reach travelers whose purpose for travel is visiting friends and relatives in advance of travel can reduce the burden of travel-related illness.

Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network.

Travelers returning to their country of origin to visit friends and relatives (VFRs) have increased risk of travel-related health problems. We examined GeoSentinel data to compare travel characteristics and illnesses acquired by 3 groups of travelers to low-income countries: VFRs who had originally been immigrants (immigrant VFRs), VFRs who had not originally been immigrants (traveler VFRs), and tourist travelers. Immigrant VFRs were predominantly male, had a higher mean age, and disproportionately required treatment as inpatients. Only 16% of immigrant VFRs sought pretravel medical advice. Proportionately more immigrant VFRs visited sub-Saharan Africa and traveled for >30 days, whereas tourist travelers more often traveled to Asia. Systemic febrile illnesses (including malaria), nondiarrheal intestinal parasitic infections, respiratory syndromes, tuberculosis, and sexually transmitted diseases were more commonly diagnosed among immigrant VFRs, whereas acute diarrhea was comparatively less frequent. Immigrant VFRs and traveler VFRs had different demographic characteristics and types of travel-related illnesses. A greater proportion of immigrant VFRs presented with serious, potentially preventable travel-related illnesses than did tourist travelers.

Spectrum of disease and relation to place of exposure among ill returned travelers.

BACKGROUND: Approximately 8 percent of travelers to the developing world require medical care during or after travel. Current understanding of morbidity profiles among ill returned travelers is based on limited data from the 1980s. METHODS: Thirty GeoSentinel sites, which are specialized travel or tropical-medicine clinics on six continents, contributed clinician-based sentinel surveillance data for 17,353 ill returned travelers. We compared the frequency of occurrence of each diagnosis among travelers returning from six developing regions of the world. RESULTS: Significant regional differences in proportionate morbidity were detected in 16 of 21 broad syndromic categories. Among travelers presenting to GeoSentinel sites, systemic febrile illness without localizing findings occurred disproportionately among those returning from sub-Saharan Africa or Southeast Asia, acute diarrhea among those returning from south central Asia, and dermatologic problems among those returning from the Caribbean or Central or South America. With respect to specific diagnoses, malaria was one of the three most frequent causes of systemic febrile illness among travelers from every region, although travelers from every region except sub-Saharan Africa and Central America had confirmed or probable dengue more frequently than malaria. Among travelers returning from sub-Saharan Africa, rickettsial infection, primarily tick-borne spotted fever, occurred more frequently than typhoid or dengue. Travelers from all regions except Southeast Asia presented with parasite-induced diarrhea more often than with bacterial diarrhea. CONCLUSIONS: When patients present to specialized clinics after travel to the developing world, travel destinations are associated with the probability of the diagnosis of certain diseases. Diagnostic approaches and empiric therapies can be guided by these destination-specific differences.

Yellow fever vaccine: an updated assessment of advanced age as a risk factor for serious adverse events.

Since 1996, the scientific community has become aware of 14 reports of yellow fever vaccine (YEL)-associated viscerotropic disease (YEL-AVD) cases and four reports of YEL-associated neurotropic disease (YEL-AND) worldwide, changing our understanding of the risks of the vaccine. Based on 722 adverse event reports after YEL submitted to the U.S. Vaccine Adverse Event Reporting System in 1990-2002, we updated the estimates of the age-adjusted reporting rates of serious adverse events, YEL-AVD and YEL-AND. We found that the reporting rates of serious adverse events were significantly higher among vaccinees aged > or =60 years than among those 19-29 years of age (reporting rate ratio = 5.9, 95% CI 1.6-22.2). Yellow fever is a serious and potentially fatal disease. For elderly travelers, the risk for severe illness and death due to yellow fever infection should be balanced against the risk of a serious adverse event due to YEL.

Yellow fever 17D vaccine safety and immunogenicity in the elderly.

The incidence of serious and severe multisystem adverse events (AEs) following yellow fever (YF) 17D vaccine is higher in persons of advanced age. One hypothesis for the occurrence of these AEs in the elderly is immunological senescence and a reduced ability to clear the vaccine virus infection. We determined age-specific rates of serious and nonserious AEs in two large clinical trials of two YF 17D vaccines from different manufacturers. In addition, we analyzed AEs reported in a large general practice data base in the United Kingdom. Neutralizing antibody responses were compared in young and elderly subjects. In the clinical trials, involving a total of 4,532 subjects, there were no neurological and viscerotropic AEs; interestingly, the incidence of common injection site and systemic AEs was significantly lower in elderly than in younger subjects. The neutralizing antibody categorical and quantitative responses were equivalent across younger and elderly subjects. In contrast, the larger retrospective analysis of 43,555 persons receiving YF 17D in the UK general practice database revealed a higher incidence of significant neurologic and multisystem AEs with advancing age. The age-specific reporting rate ratio (RRR) was approximately twice that in the 25-44 year-old reference group for subjects in the 45-64 year age group (RRR 1.82; 95% CI 0.88,3.77) and 3-fold higher for the 65-74 year-old age group (RRR 2.82; 95% CI 0.81, 9.81). These results are consistent with previous reports on YF vaccine safety in the US (Martin M, et al. Emerg Infect Dis 2001;6:945-51; Khromova et al., Vaccine 2005;23:3256-63). In elderly persons, YF 17D vaccine is associated with a higher frequency of significant AEs in the elderly but a lower incidence of common nonserious side-effects. The neutralizing antibody response, which is the mediator of protective immunity to YF, is not diminished in healthy, elderly persons.

Imported Plasmodium vivax malaria: demographic and clinical features in nonimmune travelers.

BACKGROUND: Imported malaria is an important problem in nonendemic countries due to increasing travel to and immigration from malaria-endemic countries. Plasmodium vivax malaria is relatively common in travelers but there are few published data regarding the outcome of P. vivax malaria in this group. METHODS: We analyzed 209 cases of P. vivax malaria that were reported to the GeoSentinel network and the VIDS database, Royal Melbourne Hospital. Analyses were performed on data including demographics, pretravel encounter, antimalarial prophylaxis, exposure history, type of travel, countries of recent and past travel, clinical presentation, treatment, outcome and final diagnoses. RESULTS: The majority of patients were travelers (61%), followed by expatriates (13%) and recent immigrants or foreign visitors (12%). Recent travel to Oceania, sub-Saharan Africa, and South and Central America was significantly more likely to be associated with P. vivax malaria than travel to all other regions. The clinical presentation of P. vivax malaria acquired in the Pacific region is indistinguishable from infection with P. falciparum. The use of chloroquine prophylaxis did not prolong the incubation period. Relapse of infection was not infrequent, and the only significant predictor of relapse was travel to Papua New Guinea (PNG), regardless of primaquine dose. Travelers returning from PNG were eight times more likely to relapse after primaquine treatment compared to travelers with P. vivax malaria acquired elsewhere. CONCLUSIONS: We have presented details of the epidemiology, clinical presentation and management of infection with P. vivax malaria in travelers. P. vivax malaria is an important cause of morbidity in travelers, and relapse following primaquine treatment is especially problematic with P. vivax malaria acquired in PNG.