Safety and immunogenicity of ETVAX®, an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa.

BACKGROUND: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies. METHODS: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65 years were randomized 1:1 to receive ETVAX® or placebo. They visited Benin for 12 days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence. RESULTS: The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX® recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of ≥2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX® recipients (93%) responded to either LTB or O78. CONCLUSIONS: This Phase 2b trial is the largest on ETVAX® undertaken amongst travellers to date. ETVAX® showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.

Dientamoeba fragilis - the most common intestinal protozoan in the Helsinki Metropolitan Area, Finland, 2007 to 2017.

BackgroundDespite the global distribution of the intestinal protozoan Dientamoeba fragilis, its clinical picture remains unclear. This results from underdiagnosis: microscopic screening methods either lack sensitivity (wet preparation) or fail to reveal Dientamoeba (formalin-fixed sample).AimIn a retrospective study setting, we characterised the clinical picture of dientamoebiasis and compared it with giardiasis. In addition, we evaluated an improved approach to formalin-fixed samples for suitability in Dientamoeba diagnostics.MethodsThis study comprised four parts: (i) a descriptive part scrutinising rates of Dientamoeba findings; (ii) a methodological part analysing an approach to detect Dientamoeba-like structures in formalin samples; (iii) a clinical part comparing demographics and symptoms between patients with dientamoebiasis (n = 352) and giardiasis (n = 272), and (iv) a therapeutic part (n = 89 patients) investigating correlation between faecal eradication and clinical improvement.ResultsThe rate of Dientamoeba findings increased 20-fold after introducing criteria for Dientamoeba-like structures in formalin-fixed samples (88.9% sensitivity and 83.3% specificity). A further increase was seen after implementing faecal PCR. Compared with patients with giardiasis, the symptoms in the Dientamoeba group lasted longer and more often included abdominal pain, cramping, faecal urgency and loose rather than watery stools. Resolved symptoms correlated with successful faecal eradication (p < 0.001).ConclusionsPreviously underdiagnosed, Dientamoeba has become the most frequently recorded pathogenic enteroparasite in Finland. This presumably results from improved diagnostics with either PCR or detection of Dientamoeba-like structures in formalin-fixed samples, an approach applicable also in resource-poor settings. Symptoms of dientamoebiasis differ slightly from those of giardiasis; patients with distressing symptoms require treatment.

Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data.

Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

A closer look at travellers' infections abroad: Finnish nationwide data with incidences, 2010 to 2012.

BACKGROUND: Although infections represent the most common health problem of travellers abroad, data on morbidity and incidences of various infections are scarce. METHOD: Data on infections of Finnish travellers during 2010-2012 were retrieved from the database of SOS International, an assistance organization covering 95% of Finns requiring aid abroad. The study included 30,086 cases. For incidence calculation, the data were linked to the numbers of Finns visiting these regions during the same period as recorded by the Official Statistics of Finland. RESULTS: The incidence of infections was particularly high in Africa, southern Europe plus the eastern Mediterranean, and Asia plus Oceania. The most frequent diagnoses were acute gastroenteritis (38.0%) and respiratory-tract infections (RTI) (34.5%), followed by infections of the ear (12.6%), skin or subcutaneous tissue (5.1%), urogenital tract (4.2%), eye (3.1%), and systemic febrile infections (2.2%). Vaccine-preventable diseases (VPD) accounted for 0.8% of cases, with varicella as most (49%) and influenza as second-most (27%) common. CONCLUSIONS: Incidence of infections was higher in southern than in eastern and western Europe. Gastroenteritis and RTI proved the most frequent diagnoses, whereas systemic febrile infections were uncommon. Despite pre-travel immunizations, VPDs still occurred; pre-travel consultation should cover both varicella and influenza.

Travelers' health problems and behavior: prospective study with post-travel follow-up.

BACKGROUND: The annual number of international tourist arrivals has recently exceeded one billion, yet surprisingly few studies have characterized travelers' behavior, illness, and risk factors in a prospective setting. Particularly scarce are surveys of data spanning travel, return, and follow-up of the same cohort. This study examines behavior and illness among travelers while abroad, after return home, and at follow-up. Patterns of behavior connected to type of travel and illness are characterized so as to identify risk factors and provide background data for pre-travel advice. METHODS: Volunteers to this prospective cohort study were recruited at visits to a travel clinic prior to departure. Data on the subjects' health and behavior were collected by questionnaires before and after journeys and over a three-week follow-up. In addition, the subjects were asked to fill in health diaries while traveling. RESULTS: The final study population consisted of 460 subjects, 79 % of whom reported illness during travel or on arrival: 69 % had travelers' diarrhea (TD), 17 % skin problems, 17 % fever, 12 % vomiting, 8 % respiratory tract infection, 4 % urinary tract infection, 2 % ear infection, 4 % gastrointestinal complaints other than TD or vomiting, and 4 % other symptoms. Of all subjects, 10 % consulted a doctor and 0.7 % were hospitalized; 18 % took antimicrobials, with TD as the most common indication (64 %). Ongoing symptoms were reported by 25 % of all travelers upon return home. During the three-week follow-up (return rate 51 %), 32 % of respondents developed new-onset symptoms, 20 % visited a doctor and 1.7 % were hospitalized. Factors predisposing to health problems were identified by multivariable analysis: certain regions (Southern Asia, South-Eastern Asia, and Eastern Africa), female gender, young age, and long travel duration. CONCLUSIONS: Despite proper preventive measures like vaccinations, malaria prophylaxis, and travel advice, the majority of our subjects fell ill during or after travel. As the symptoms mostly remained mild, health care services were seldom needed. Typical traveler profiles were identified, thereby providing a tool for pre-travel advice. The finding that one third reported new-onset illness during follow-up attests to the importance of advising clients on potential post-travel health problems already during pre-travel visits.

Imported malaria in Finland 2003-2011: prospective nationwide data with rechecked background information.

BACKGROUND: Although described in several reports, imported malaria in Europe has not been surveyed nationwide with overall coverage of patients and individually rechecked background information. Plasmodium falciparum infections have been reported despite regularly taken appropriate chemoprophylaxis, yet the reliability of such questionnaire-based retrospective data has been questioned. This was the starting-point for conducting a prospective nationwide survey of imported malaria where compliance data was double-checked. METHODS: Data was collected on all cases of imported malaria confirmed and recorded by the reference laboratory of Finland (population 5.4 million) from 2003 to 2011, and these were compared with those reported to the National Infectious Disease Register (NIDR). Background information was gathered by detailed questionnaires sent to the clinicians upon diagnosis; missing data were enquired by telephone of clinician or patient. Special attention was paid to compliance with chemoprophylaxis: self-reported use of anti-malarials was rechecked for all cases of P. falciparum. RESULTS: A total of 265 malaria cases (average annual incidence rate 0.5/100,000 population) had been recorded by the reference laboratory, all of them also reported to NIDR: 54% were born in malaria-endemic countries; 86% were currently living in non-endemic regions. Malaria was mainly (81%) contracted in sub-Saharan Africa. Plasmodium falciparum proved to be the most common species (72%). Immigrants constituted the largest group of travellers (44%). Pre-travel advice was received by 20% of those born in endemic regions and 81% of those from non-endemic regions. Of those with P. falciparum, 4% reported regular use of appropriate chemoprophylaxis (mefloquine or atovaquone/proguanil or doxycycline for regions with chloroquine-resistant and atovaquone/proguanil or doxycycline for regions with mefloquine-resistant P. falciparum); after individual rechecking, however, it was found that none of them had been fully compliant. CONCLUSIONS: Information on compliance with chemoprophylactic regimen cannot be relied on, and it should be rechecked if malaria is suspected. The results of the present study suggest that mefloquine, atovaquone/proguanil and doxycycline are effective as chemoprophylaxis against P. falciparum malaria, when taken conscientiously.

Fever with rash in patients returning from popular tourist resort Phuket, Thailand: dengue--or measles?

We report three recent cases of measles in travelers to a popular vacation resort, Phuket, Thailand, two initially diagnosed clinically as dengue, one as drug reaction. In countries with no indigenous measles, clinicians may no longer recognize the disease. When left misdiagnosed, the patients continue to be potential transmitters.

Personal protective equipment management and policies: European Network for Highly Infectious Diseases data from 48 isolation facilities in 16 European countries.

OBJECTIVE: To collect data about personal protective equipment (PPE) management and to provide indications for improving PPE policies in Europe. DESIGN: Descriptive, cross-sectional survey. SETTING AND PARTICIPANTS: Data were collected in 48 isolation facilities in 16 European countries nominated by National Health Authorities for the management of highly infectious diseases (HIDs). METHODS: Data were collected through standardized checklists at on-site visits during February-November 2009. Indications for adequate PPE policies were developed on the basis of a literature review, partners' expert opinions, and the collected data. RESULTS: All facilities have procedures for the selection of PPE in case of HID, and 44 have procedures for the removal of PPE. In 40 facilities, different levels of PPE are used according to a risk assessment process, and in 8 facilities, high-level PPE (e.g., positive-pressure complete suits or Trexler units) is always used. A fit test is performed at 25 of the 40 facilities at which it is applicable, a seal check is recommended at 25, and both procedures are used at 17. Strategies for promoting and monitoring the correct use of PPE are available at 42 facilities. In case of a sudden increase in demand, 44 facilities have procedures for rapid supply of PPE, whereas 14 facilities have procedures for decontamination and reuse of some PPE. CONCLUSIONS: Most isolation facilities devote an acceptable level of attention to PPE selection and removal, strategies for the promotion of the correct use of PPE, and ensuring adequate supplies of PPE. Fit test and seal check procedures are still not widely practiced. Moreover, policies vary widely between and within European countries, and the development of common practice procedures is advisable.

Plasmodium falciparum--malaria in pregnant African immigrants often goes unrecognized.

We report four cases of asymptomatic Plasmodium falciparum malaria in pregnant African women. They had immigrated to Finland 3 to 13 months earlier. The disease was revealed only by anemia. The diagnosis relied on blood smear which showed a parasitemia <0.2% in three cases. Medical personnel should be informed about the possibility of afebrile forms of malaria in pregnant women even months after immigration. Very low levels of parasitemia may call for a more sensitive diagnostic approach such as polymerase chain reaction.

Fever in travelers returning from malaria-endemic areas: don't look for malaria only.

BACKGROUND: Returning travelers with fever pose challenges for clinicians because of the multitude of diagnostic alternatives. Case data in a Finnish tertiary hospital were analyzed in order to define the causes of fever in returned travelers and to evaluate the current diagnostic approach. METHODS: A retrospective study of patient records comprised 462 febrile adults who, after traveling in malaria-endemic areas, were admitted to the Helsinki University Central Hospital (HUCH) emergency room from 2005 to 2009. These patients were identified through requests for malaria smear. RESULTS: The most common groups of diagnoses were acute diarrheal disease (126 patients/27%), systemic febrile illness (95/21%), and respiratory illness (69/15%). The most common specific main diagnosis was Campylobacter infection (40/9%). Malaria was diagnosed in 4% (20/462). Blood culture was positive for bacteria in 5% of those tested (21/428). Eight patients were diagnosed with influenza. HIV-antibodies were tested in 174 patients (38%) and proved positive in 3% of them (5/174, 1% of all patients). The cause of fever was noninfectious in 12 (3%), remaining unknown in 116 (25%). Potentially life-threatening illnesses were diagnosed in 118 patients (26%), the strongest risk factors were baseline C-reactive protein (CRP) ≥100 (OR 3.6; 95% CI 2.0-6.4) and platelet count ≤140 (OR 3.8; 95% CI 2.0-7.3). Nine patients (2%) were treated in high dependency or intensive care units; one died of septicemia. Forty-five patients (10%) had more than one diagnosis. CONCLUSION: The high proportion of patients with more than one diagnosis proves the importance of careful diagnostics. Every fourth returning traveler with fever had a potentially life-threatening illness. Septicemia was as common as malaria. The proportion of HIV cases exceeded the prevalence in population for which Centers for Disease Control and Prevention, USA (CDC) recommends routine HIV testing. Both blood cultures and HIV tests should be considered in febrile travelers.

Imported malaria in Finland 1995 to 2008: an overview of surveillance, travel trends, and antimalarial drug sales.

BACKGROUND: To improve pre-travel advice, we analyzed nationwide population-based surveillance data on malaria cases reported to the National Infectious Disease Register of Finland (population 5.3 million) during 1995 to 2008 and related it to data on traveling and antimalarial drug sales. METHODS: Surveillance data comprised information on malaria cases reported to the National Infectious Disease Register during 1995 to 2008. Traveling data were obtained from Statistics Finland (SF) and the Association of Finnish Travel Agents (AFTA). SF data included information on overnight leisure trips to malaria-endemic countries during 2000 to 2008. AFTA data included annual number of organized trips during 1999 to 2007. Quarterly numbers of antimalarial drug sales were obtained from the Finnish Medicines Agency. Descriptive and time series analyses were performed. RESULTS: A total of 484 malaria cases (average annual incidence 0.7/100,000 population) were reported; 283 patients were Finnish- and 201 foreign-born. In all, 15% of all cases were children; 72% foreign- and 28% Finnish-born. Malaria infections were mostly acquired in Africa (76%). Among foreign-born cases, 89% of the infections were acquired in the region of birth. The most common species were Plasmodium falciparum (61%) and Plasmodium vivax (22%). Although traveling to malaria-endemic areas increased, no increase occurred in malaria cases, and a decreasing trend was present in antimalarial drug sales. Traveling to malaria-endemic countries and drug sales followed the same seasonal pattern, with peaks in the first and last quarter of the year. CONCLUSIONS: More efforts should be focused on disseminating pre-travel advice to immigrants planning to visit friends and relatives and travelers on self-organized trips.

The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator?

BACKGROUND: The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers. METHODS: Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries. RESULTS: In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years. CONCLUSION: The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It is proposed to use a threshold incidence of > 1 case per 100,000 visits to consider targeted malaria prophylaxis recommendations to minimize use of chemoprophylaxis for low risk exposure during visits to S-E Asia. Policy needs to be adjusted regularly to reflect the changing risk.

Fatal babesiosis in man, Finland, 2004.

We report an unusual case of human babesiosis in Finland in a 53-year-old man with no history of splenectomy. He had a rudimentary spleen, coexisting Lyme borreliosis, exceptional dark streaks on his extremities, and subsequent disseminated aspergillosis. He was infected with Babesia divergens, which usually causes bovine babesiosis in Finland.

[Pregnancy and travelling]. / Raskaus ja matkustaminen.

Healthy pregnant women can, in general, travel safely even to exotic destinations. Vaccines, medication and insurance coverage should be considered in advance. Chronic disease or pregnancy complications call for medical consultation beforehand. In advanced pregnancy, travel is restricted by commercial airlines. Low molecular weight heparin may be used to prevent deep vein thrombosis in risk groups during long flights. If travel to malaria areas cannot be avoided, chemoprophylaxis must be taken. The need for vaccinations must be assessed individually, according to risks. Killed vaccines are considered safe; live attenuated preparations are not recommended.

Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease.

The European Network for Infectious Diseases (EUNID) is a network of clinicians, public health epidemiologists, microbiologists, infection control, and critical-care doctors from the European member states, who are experienced in the management of patients with highly infectious diseases. We aim to develop a consensus recommendation for infection control during clinical management and invasive procedures in such patients. After an extensive literature review, draft recommendations were amended jointly by 27 partners from 15 European countries. Recommendations include repetitive training of staff to ascertain infection control, systematic use of cough and respiratory etiquette at admission to the emergency department, fluid sampling in the isolation room, and analyses in biosafety level 3/4 laboratories, and preference for point-of-care bedside laboratory tests. Children should be cared for by paediatricians and intensive-care patients should be cared for by critical-care doctors in high-level isolation units (HLIU). Invasive procedures should be avoided if unnecessary or done in the HLIU, as should chest radiography, ultrasonography, and renal dialysis. Procedures that require transport of patients out of the HLIU should be done during designated sessions or hours in secure transport. Picture archiving and communication systems should be used. Post-mortem examination should be avoided; biopsy or blood collection is preferred.

Japanese encephalitis in a Finnish traveler on a two-week holiday in Thailand.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus, and one of the leading causes of epidemic encephalitis in Southeast Asia. Reports of symptomatic JEV encephalitis in tourists have been rare. We describe a case of symptomatic JE transmitted in 2004 during a short two-week trip to common tourist attractions in Thailand.

Molecular epidemiology of dengue virus strains from Finnish travelers.

We characterized 11 dengue virus (DENV) isolates obtained from Finnish travelers during 2000-2005 using monoclonal antibodies and phylogenetic analysis. The analysis of DENV isolated from travelers contributes to the global picture of strain distribution and circulation. The isolates included all serotypes, including a DENV-2 isolate from Ghana.

The low and declining risk of malaria in travellers to Latin America: is there still an indication for chemoprophylaxis?

A comparison was made between local malaria transmission and malaria imported by travellers to identify the utility of national and regional annual parasite index (API) in predicting malaria risk and its value in generating recommendations on malaria prophylaxis for travellers. Regional malaria transmission data was correlated with malaria acquired in Latin America and imported into the USA and nine European countries. Between 2000 and 2004, most countries reported declining malaria transmission. Highest API's in 2003/4 were in Surinam (287.4) Guyana (209.2) and French Guiana (147.4). The major source of travel associated malaria was Honduras, French Guiana, Guatemala, Mexico and Ecuador. During 2004 there were 6.3 million visits from the ten study countries and in 2005, 209 cases of malaria of which 22 (11%) were Plasmodium falciparum. The risk of adverse events are high and the benefit of avoided benign vivax malaria is very low under current policy, which may be causing more harm than benefit.

Severe dengue virus infection in travelers: risk factors and laboratory indicators.

BACKGROUND: Dengue fever is the most common arboviral disease in travelers. In countries where dengue virus is endemic, sequential (secondary) infections with different dengue virus serotypes are associated with disease severity. Data on severity and secondary infection rates in a population of travelers are lacking. METHODS: Intensified surveillance of dengue fever in travelers was performed within the European Network on Surveillance of Imported Infectious Diseases. Data were collected at 14 European clinical referral centers between 2003 and 2005. RESULTS: A total of 219 dengue virus infections imported from various regions of endemicity were reported. Serological analysis revealed a secondary immune response in 17%. Spontaneous bleeding was observed in 17 (8%) patients and was associated with increased serum alanine and aspartate aminotransferase levels and lower median platelet counts. Two (0.9%) patients fulfilled the World Health Organization (WHO) case definition for dengue hemorrhagic fever. However, 23 (11%) travelers had severe clinical manifestations (internal hemorrhage, plasma leakage, shock, or marked thrombocytopenia). A secondary immune response was significantly associated with both spontaneous bleeding and other severe clinical manifestations. CONCLUSIONS: In travelers, severe dengue virus infections are not uncommon but may be missed if the WHO classification is strictly applied. High liver enzyme levels and low platelet counts could serve as indicators of disease severity.