Delayed-onset hemolytic anemia in patients with travel-associated severe malaria treated with artesunate, France, 2011-2013.

Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate.

Severe delayed autoimmune haemolytic anaemia following artesunate administration in severe malaria: a case report.

BACKGROUND: Parenteral artesunate is recommended as first-line therapy for severe and complicated malaria. Although its efficacy has been proven, long-term safety profile is still under evaluation. Several cases of delayed haemolytic anaemia occurred after initial clinical improvement and resolution of parasitaemia in non-immune travellers and children living in endemic areas. Reports have generated concern that this phenomenon might be related to the treatment itself, either by direct toxicity or immune-related mechanism. This is a report of the first case of autoimmune haemolytic anaemia following treatment of severe malaria initially managed with parenteral artesunate with strong indication for drug-immune related mechanism. CASE: A 17-year old Ivoirian female travelling in France presented with fever, headache and abdominal pain seven days after her arrival. Physical examination was indicative of septic shock while blood analysis showed normal haemoglobin level, but profound thrombocytopaenia and hyperlactataemia. Blood smear analysis showed Plasmodium falciparum infection with a parasitaemia of 0.8%. Severe malaria was diagnosed according to the WHO criteria. The patient was initially managed with artemether/lumefantrine combination and then parenteral artesunate for 48 hours. Empiric antibiotic course was also initiated with ceftriaxone, metronidazole, gentamycin, and then piperacillin and ciprofloxacin. At day 14, haemoglobin dropped to 4.6 g/dL with biologic features indicative of haemolysis (LDH 658 U/L, haptoglobin<0.15 g/L). At that time, parasitaemia was negative and other infections or hereditary disorders were excluded, while Coombs' direct antiglobulin test was positive for IgG and C3d. Antinuclear antibodies were absent. Further investigations evidenced drug-induced antibodies related to artesunate. It was concluded a drug-mediated autoimmune haemolytic anaemia. A corticosteroids regimen was initiated at 1 mg/kg/day. Outcome was favourable and corticosteroids were progressively tapered during two months. At present the patient's condition remains stable without recurrence of haemolytic anaemia. CONCLUSION: This is the first case of delayed haemolytic anaemia related to artesunate with a strong indication for drug-immune related mechanism. Further research is warranted to better characterize this plausible cause of post-treatment haemolysis following parenteral artesunate administration in severe malaria patients.

Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE).

OBJECTIVES: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. METHODS: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. RESULTS: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. DISCUSSION: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

Quinine-resistant malaria in traveler returning from Senegal, 2007.

We describe clinical and parasitologic features of in vivo and in vitro Plasmodium falciparum resistance to quinine in a nonimmune traveler who returned to France from Senegal in 2007 with severe imported malaria. Clinical quinine failure was associated with a 50% inhibitory concentration of 829 nmol/L. Increased vigilance is required during treatment follow-up.

Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection (COVID-19): A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatients aged 65 years or older (COVERAGE trial).

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8th, 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8th, 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15th, 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15th, 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22nd, 2020 (Identifier: NCT04356495): and on EudraCT on April 10th, 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies.

BACKGROUND: Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood. CASE PRESENTATION: We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection. CONCLUSIONS: Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.

An imported case of Chikungunya fever from Madagascar: use of the sentinel traveller for detecting emerging arboviral infections in tropical and European countries.

A major Chikungunya virus (CHIKV) epidemic affected the South-Western Indian Ocean islands in 2005. This major outbreak raised concerns about the possibility of the emergence of CHIKV infections in Europe as an autochthonous CHIKV outbreak occurred in the Ravenna region of Italy during the summer of 2007 and was linked to a viraemic index case originating in Kerala, India. This report highlights the need for surveillance in countries where such emerging infections could be introduced by returning travellers.

Early complicated schistosomiasis in a returning traveller: Key contribution of new molecular diagnostic methods.

Early schistosomiasis poses a serious diagnostic challenge, because current standard diagnostic techniques based on serology and egg microscopy lack sensitivity at the initial presentation. We report spinal cord neuroschistosomiasis in a traveller developing 6 weeks after exposure. The diagnosis was confirmed by Schistosoma mansoni-targeted real-time PCR in blood and cerebrospinal fluid, before the results of conventional methods became positive. Molecular assays represent a paradigm shift for the difficult diagnosis of early schistosomiasis and related complications.

Travel-related health events and their risk factors in HIV-infected sub-Saharan migrants living in France and visiting their native country: The ANRS VIHVO cohort study.

BACKGROUND: Literature on health events in HIV-infected travellers is scarce, particularly in sub-Saharan African (SSA) migrants. METHODS: We investigated health events in HIV-infected SSA migrants living in France during and after travel to their native country. All had a pre-travel plasma viral load (pVL) below 200 copies/mL and were on stable combined antiretroviral therapy (cART). Logistic regression models were used to assess the risk factors for at least one adverse health event or febrile event. RESULTS: Among 264 HIV migrants, pre-travel median CD4 count was 439/mm3 and 27 migrants (6%) experienced a low-level viremia between 50 and 200 copies/mL. One hundred (38%) experienced at least one event (13 experienced two events). The most common events were gastrointestinal, including diarrhoea (n = 29, 26%), respiratory events (n = 20, 18%), and malaria (n = 17, 15%; 1 death). In multivariable analysis, a pre-travel low-level viremia and a lack of pre-travel medical advice significantly increased the risk for any event (OR 4.31, 95% CI, 1.41-13.1; and OR 3.62, 95% CI, 1.38-9.47; respectively). A lack of pre-travel advice significantly increased the risk for febrile event. CONCLUSIONS: Early and tailored counselling on pre-travel medical advice regarding diarrhoea and vector-borne diseases prophylactic measures in HIV-infected SSA migrants should be emphasised before travel to Africa.

Evaluation of FRET real-time PCR assay for rapid detection and differentiation of Plasmodium species in returning travellers and migrants.

BACKGROUND: A simple real-time PCR assay using one set of primer and probe for rapid, sensitive and quantitative detection of Plasmodium species, with simultaneous differentiation of Plasmodium falciparum from the three other Plasmodium species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae) in febrile returning travellers and migrants was developed and evaluated. METHODS: Consensus primers were used to amplify a species-specific region of the multicopy 18S rRNA gene, and fluorescence resonance energy transfer hybridization probes were used for detection in a LightCycler platform (Roche). The anchor probe sequence was designed to be perfect matches to the 18S rRNA gene of the fourth Plasmodium species, while the acceptor probe sequence was designed for P. falciparum over a region containing one mismatched, which allowed differentiation of the three other Plasmodium species. The performance characteristics of the real-time PCR assay were compared with those of conventional PCR and microscopy-based diagnosis from 119 individuals with a suspected clinical diagnostic of imported malaria. RESULTS: Blood samples with parasite densities less than 0.01% were all detected, and analytical sensitivity was 0.5 parasite per PCR reaction. The melt curve means Tms (standard deviation) in clinical isolates were 60.5 degrees C (0.6 degrees C) for P. falciparum infection and 64.6 degrees C (1.8 degrees C) for non-P. falciparum species. These Tms values of the P. falciparum or non-P. falciparum species did not vary with the geographic origin of the parasite. The real-time PCR results correlated with conventional PCR using both genus-specific (Kappa coefficient: 0.95, 95% confidence interval: 0.9 - 1) or P. falciparum-specific (0.91, 0.8 - 1) primers, or with the microscopy results (0.70, 0.6 - 0.8). The real-time assay was 100% sensitive and specific for differentiation of P. falciparum to non-P. falciparum species, compared with conventional PCR or microscopy. The real-time PCR assay can also detect individuals with mixed infections (P. falciparum and non-P. falciparum sp.) in the same sample. CONCLUSION: This real-time PCR assay with melting curve analysis is rapid, and specific for the detection and differentiation of P. falciparum to other Plasmodium species. The suitability for routine use of this assay in clinical diagnostic laboratories is discussed.

Reimbursement of malaria chemoprophylaxis for travellers from Europe to Sub-Saharan Africa: Cost-effectiveness analysis from the perspective of the French national health insurance system.

Among Western countries, France has the highest incidence of imported malaria cases, mostly from travellers visiting Sub-Saharan Africa (SSA). Despite related high costs of imported malaria assumed by the public French national health insurance system (FHS), the latter does not reimburse travellers for malaria chemoprophylaxis (MC). This study aims to analyzes, from the FHS perspective, the cost-effectiveness of a 65% reimbursement of MC costs (MC 65%) for French resident travellers, under the assumption that this reimbursement would lead to increased recourse to MC. For that purpose, a decision tree model was developed with variables obtained from the literature, including incidence of malaria among travellers in the absence of MC, probabilities of recourse to MC, MC effectiveness and costs and medical expenses for a case of imported malaria. Data analysis of 1,434,675 travellers to SSA in 2005 estimated, for MC 65% vs. MC 0%, incidence of malaria cases to be 3836 malaria cases (21 deaths)/year vs. 6321 cases (34 deaths)/year, respectively, and cost of Euro 47,071,687/year vs. Euro 17,416,955/year. Incremental cost of MC 65% related to MC 0% was Euro 11,933 per malaria case prevented and Euro 2,281,133 per malaria-related death prevented. Results generated by this model, which can be adapted for other European countries, should be an incentive for the FHS to favourably consider MC 65% for French residents travelling to SSA.

Ectopic cutaneous schistosomiasis-perigenital infiltrative granulomata in a 34-year-old French pregnant woman.

Schistosomiasis, an infection with the three anthropophilic species of Schistosoma, is endemic throughout wide areas of the tropics and subtropics with an estimated rate of over 200 million people infected worldwide. Whereas symptoms and signs of vesical and gastrointestinal forms of the infection are recognized readily, cutaneous manifestations are still a challenging diagnosis particularly in Western countries. A case is described of a 34-year-old Caucasian pregnant woman who presented to our department and was diagnosed with a cutaneous schistosomiasis involvement of the perianal region. Shistosoma haematobium was shown to be present in the lesion by histopathology and was considered to be the causative organism of the disease. Treatment with a course of oral praziquantel in a dose of 40mg/kg allowed resolution of the symptoms.

Dual infection by chikungunya virus and other imported infectious agent in a traveller returning from India.

Chikungunya virus infection is a vector-borne self-limiting disease. Recent outbreaks in the Indian Ocean islands have drawn attention to the condition. Nevertheless, only a few reports of co-infection with other communicable agents have been reported. The case described now is of a traveller returning from India with concomitant documented chikungunya virus infection associated with systemic amoebiasis. This report highlights the multifaceted pathology that can be encountered with tropical infections.

Cluster of eosinophilic meningitis attributable to Angiostrongylus cantonensis infection in French policemen troop returning from the Pacific Islands.

BACKGROUND: Outbreaks of eosinophilic meningitis are reported rarely, even in regions of endemic infestation with the roundworm Angiostrongylus cantonensis, such as the Pacific Basin. We report a cluster of eosinophilic meningitis presumably attributable to A. cantonensis among French policemen returning from French Polynesia. METHODS: A retrospective cohort study among French policemen who had stayed in Tahiti was conducted using a clinical definition of eosinophilic meningitis that included severe headache within 30 days after return and eosinophilia, and who consumed locally exotic ethnic dishes with uncooked freshwater prawns. RESULTS: Five persons met the case definition for eosinophilic meningitis. Corticosteroid therapy associated with antihelminthic regimen led to improvement of symptoms in one patient. Other patients were treated with albendazole alone. All patients recovered. CONCLUSION: Among travellers at risk, the presence of severe headache and eosinophilia combined with a consistent exposure history to exotic food should alert to the possibility of A. cantonensis infestation. Travellers should be aware of the risk of infection associated with eating exotic ethnic dishes.

Expatriates in high-UV index and tropical countries: sun exposure and protection behavior in 9,416 French adults.

BACKGROUND: Overexposure to sunlight during long stays in tropical countries can reveal short- and long-term harmful effects on the skin of Caucasian residents, especially for fair-skinned subjects. The aim of this study was to describe sun exposure and sun protection behaviors during lifetime among French adults who declared having experienced at least one expatriation period in tropical or high-sun index areas for a duration of more than three consecutive months. METHODS: A self-reported questionnaire on sun exposure behavior was addressed two times, in 1997 and 2001, to the 12,741 French adult volunteers enrolled in the SU.VI.MAX cohort. A total of 8,084 subjects answered to the first survey and 1,332 additional responders answered to the second. Among the 9,416 individuals, 1,594 (652 women and 942 men) corresponded to expatriates and the remaining 7,822 to nonexpatriates (4,972 women and 2,850 men). A descriptive analysis of sun exposure and sun protection behaviors during lifetime of expatriates and nonexpatriates was performed by gender. RESULTS: Among women, 39% of expatriates belonged to the 50 to 60 class of age at inclusion, versus 33% in nonexpatriates (72 and 55% in men, respectively). In women, expatriates declared more frequently having during lifetime exposed voluntarily their skin to the sun, practiced tanning between 11 a.m. and 4 p.m., less gradually exposed their skin, experienced intensive sun exposure, and exposed their skin during nautical sports and practiced naturism. In men, expatriates declared more frequently having experienced intensive sun exposure and exposed their skin during outdoor occupations and during nautical and mountain sports. CONCLUSIONS: Although expatriates are aware of travel health advices concerning the countries where they planned to stay, they are usually poorly informed about sun exposure risk factors. Such individuals who planned to expatriate in countries with a high ultraviolet index should benefit from a visit to a travel clinic including specific health care information for risk related to sun exposure, ie, skin cancers and photoaging.

Haemoglobinuria in a 38-year-old French expatriate man living in Cameroon following artemisinin-based antimalarial treatment.

Massive haemoglobinuria is encountered rarely during the course of malaria. It is usually considered a diagnostic criterion for severe malaria, together with anaemia, acute renal failure and jaundice. Haemoglobinuria can also present among expatriates travelling to endemic areas following repeated exposure to quinoline or arylaminoalcohol drugs. A case is described of haemoglobinuria developing in a 38-year-old French expatriate diagnosed concurrently with numerous tropical infections, and treated on presumptive basis with an antimalarial regimen containing artemisinin derivatives. Haemoglobinuria resolved spontaneously within a few days. Although this case does not definitely indicate a causal link between haemoglobinuria and artemisinin derivatives, the risk of such infrequent side-effects should be taken into account in pharmacovigilance monitoring. Moreover, the patient illustrates the multifaceted pathology that can be encountered with tropical infections.

Travellers to high UV-index countries: sun-exposure behaviour in 7822 French adults.

BACKGROUND: Travel health information includes warning on sun exposure, particularly for fair-skinned individuals travelling to tropical countries. METHOD: A self-completed questionnaire on sun exposure behaviour was sent to the 12,741 French adults enrolled in the SU.VI.MAX cohort. Among the 7822 participants, 196 (110 women and 86 men) declared at least one visit to a high UV-index country over the past year for more than 1 month, subsequently referred to as long-term travellers. The remaining 7626 participants (non-travellers) accounted for 4862 women and 2764 men. RESULTS: Women travellers declared more frequently skin exposure to the sun over the past year, practised tanning in high UV-index areas more than 2h daily, experienced intensive sun exposure than non-travellers. Moreover, they asserted that basking in the sun is very important. Comparable results were found in men. The use of sun protection products was similar in travellers and non-travellers, but women tended to use sunscreen products more often, more regularly and with a higher sun protection factor (SPF) than men. CONCLUSIONS: Specific health education campaigns and pre-travel advice aiming to reduce sun exposure and to improve protective measures against ultraviolet (UV) radiation should be addressed to travellers to countries with high UV-index.