Travel-related leptospirosis in the Netherlands 2009-2016: An epidemiological report and case series.

BACKGROUND: Leptospirosis is a potentially fatal zoonotic disease that is prevalent in travellers. Here, we describe epidemiological and diagnostic characteristics of all returning travellers diagnosed with leptospirosis in the Netherlands between 2009 and 2016. Furthermore, we present a detailed clinical case series of all travellers with leptospirosis who presented at the Academic Medical Center (AMC) in the same period. METHOD: We extracted data from the records of the Dutch Leptospirosis Reference Center (NRL) of all cases of leptospirosis in travellers in the Netherlands from 2009 to 2016. Patients who presented at the AMC were identified and clinical data were extracted from the hospital records. RESULTS: 224 cases of travel-related leptospirosis were included. An increase of cases was observed from 2014 onwards. The majority of cases were male (78.1%), and had travelled to South-East Asia (62.1%). Of 41 AMC cases, 53.7% were hospitalised, but most patients had a relatively mild disease course, with no fatalities. A longer delay in diagnosis and treatment initiation existed in hospitalised compared to non-hospitalised patients, suggesting a benefit of early recognition and treatment. CONCLUSIONS: Leptospirosis was increasingly observed in returning travellers in the Netherlands, and is a diagnosis that should be considered in any returning febrile traveller.

Comparison of the PRNT and an immune fluorescence assay in yellow fever vaccinees receiving immunosuppressive medication.

BACKGROUND: The 17D-yellow fever (YF) vaccination is considered contraindicated in immune-compromised patients; however, accidental vaccination occurs. In this population, measuring the immune response is useful in clinical practice. METHODS: In this study we compare two antibody tests (the Immune Fluorescence Assay and the Plaque Reduction Neutralization Test) in a group of Dutch immune-compromised travellers with a median of 33 days (IQR [28-49]) after primary YF vaccination. RESULTS: We collected samples of 15 immune-compromised vaccinees vaccinated with the 17D yellow fever vaccine between 2004 and 2012. All samples measured in the plaque reduction neutralization test yielded positive results (>80% virus neutralization with a 1:10 serum dilution). Immune Fluorescence Assay sensitivity was 28% (95% CI [0.12-0.49]). No adverse events were reported. CONCLUSIONS: All immune-compromised patients mounted an adequate response with protective levels of virus neutralizing antibodies to the 17-D YF vaccine. No adverse effects were reported. Compared to the plaque reduction neutralization test, the sensitivity of the Immune Fluorescence Assay test was low. Further research is needed to ascertain that 17D vaccination in immune-compromised patients is safe.

[Travel advice and vaccinations in patients with chronic inflammatory diseases: the earlier, the better]. / Reisadvies en vaccinaties bij chronische ontstekingsziekten: hoe eerder, hoe beter.

The number of patients with chronic inflammatory diseases who have been travelling to the tropics or subtropics has been rising. Use of immunomodulating drugs increases the risk for infectious diseases and may reduce seroprotection rates following vaccination. In addition, live vaccines, such as the yellow fever vaccine, are contra-indicated. Patients and their physicians are not always aware of the consequences of the use of immunomodulating drugs for travel and this may lead to undesirable situations, including last-minute cancellation of the trip. Informing and vaccinating patients early after the diagnosis of the inflammatory disease may prevent these undesirable situations.

Severe murine typhus with pulmonary system involvement.

We encountered a case of severe murine typhus complicated by acute respiratory distress syndrome. To determine worldwide prevalence of such cases, we reviewed the literature and found that respiratory symptoms occur in ≈30% of murine typhus patients. In disease-endemic areas, murine typhus should be considered for patients with respiratory symptoms and fever.

Species-directed therapy for leishmaniasis in returning travellers: a comprehensive guide.

BACKGROUND: Leishmaniasis is increasingly reported among travellers. Leishmania species vary in sensitivity to available therapies. Fast and reliable molecular techniques have made species-directed treatment feasible. Many treatment trials have been designed poorly, thus developing evidence-based guidelines for species-directed treatment is difficult. Published guidelines on leishmaniasis in travellers do not aim to be comprehensive or do not quantify overall treatment success for available therapies. We aimed at providing comprehensive species-directed treatment guidelines. METHODOLOGY/PRINCIPAL FINDINGS: English literature was searched using PubMed. Trials and observational studies were included if all cases were parasitologically confirmed, the Leishmania species was known, clear clinical end-points and time points for evaluation of treatment success were defined, duration of follow-up was adequate and loss to follow-up was acceptable. The proportion of successful treatment responses was pooled using mixed effects methods to estimate the efficacy of specific therapies. Final ranking of treatment options was done by an expert panel based on pooled efficacy estimates and practical considerations. 168 studies were included, with 287 treatment arms. Based on Leishmania species, symptoms and geography, 25 clinical categories were defined and therapy options ranked. In 12/25 categories, proposed treatment agreed with highest efficacy data from literature. For 5/25 categories no literature was found, and in 8/25 categories treatment advise differed from literature evidence. For uncomplicated cutaneous leishmaniasis, combination of intralesional antimony with cryotherapy is advised, except for L. guyanensis and L. braziliensis infections, for which systemic treatment is preferred. Treatment of complicated (muco)cutaneous leishmaniasis differs per species. For visceral leishmaniasis, liposomal amphotericin B is treatment of choice. CONCLUSIONS/SIGNIFICANCE: Our study highlights current knowledge about species-directed therapy of leishmaniasis in returning travellers and also demonstrates lack of evidence for treatment of several clinical categories. New data can easily be incorporated in the presented overview. Updates will be of use for clinical decision making and for defining further research.

LeishMan recommendations for treatment of cutaneous and mucosal leishmaniasis in travelers, 2014.

BACKGROUND: Treatment of cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) in travelers is still controversial. Over the last decade, national and international consortia have published recommendations for treating CL in travelers. These guidelines harmonize many issues, but there are some discrepancies. METHODS: Leishmania parasites causing CL can now be genotyped by polymerase chain reaction techniques for detecting Leishmania DNA. Therefore, treatment recommendations can now be species based rather than based on geographical exposure. To review the evidence on which the recommendations were based, "LeishMan" (Leishmaniasis Management), a group of experts from 13 institutions in eight European countries, performed a PubMed MEDLINE) literature search and considered unpublished evidence and the experts' own personal experiences. The Oxford evidence grading system was used to evaluate the information. RESULTS AND CONCLUSION: In this article, the authors provide practical treatment recommendations for imported CL and ML in Europe, drawn up from the review by the European experts.

Trends in the knowledge, attitudes and practices of travel risk groups toward prevention of hepatitis B: results from the repeated cross-sectional Dutch Schiphol Airport Survey 2002-2009.

BACKGROUND: Previous studies investigating the travellers' knowledge, attitudes and practices (KAP) profile indicated an important educational need among those travelling to risk destinations. METHODS: In the years 2002-2009 an annually repeated cross-sectional questionnaire-based survey was conducted at the Dutch Schiphol Airport with the aim to study trends in KAP of travel risk groups toward prevention of hepatitis B. The frequently encountered risk groups last-minute travellers, solo-travellers, business travellers, travellers visiting friends and relatives (VFR) and elderly travellers were specifically studied. RESULTS: A total of 3045 respondents were included in the survey. Travellers to destinations with a high risk for hepatitis B had significantly less accurate risk perceptions (knowledge) than travellers to low-risk destinations but no differences were observed in past risk-taking attitude. Protection rates against hepatitis B were significantly higher in travellers to high-risk destinations. There was a positive trend over the years in the proportion of travellers to high-risk destinations seeking travel health advice. In accordance with this, trend analyses also indicated rising protection rates against hepatitis B. No significant trends in protection over time were observed for the travel risk groups. CONCLUSIONS: The results of this repeated cross-sectional survey suggest an annual 10% increase in protection rates against hepatitis B in Dutch travellers, both to destinations with a high risk and to destinations with a lower risk of hepatitis B, but these trends in protection rates were not observed for the travel risk groups to high-risk destinations. The KAP profile of last-minute travellers and (to a lesser extent) VFRs showed an increased relative risk in hepatitis B, irrespective of the travel destination, underlining the need for specific targeting of these travel risk groups.

Trends in the knowledge, attitudes and practices of travel risk groups towards prevention of malaria: results from the Dutch Schiphol Airport Survey 2002 to 2009.

BACKGROUND: Previous studies investigating the travellers' knowledge, attitudes and practices (KAP) profile indicated an important educational need among those travelling to risk destinations. Initiatives to improve such education should target all groups of travellers, including business travellers, those visiting friends and relatives (VFRs), and elderly travellers. METHODS: In the years 2002 to 2009, a questionnaire-based survey was conducted at the Dutch Schiphol Airport with the aim to study trends in KAP of travel risk groups towards prevention of malaria. The risk groups last-minute travellers, solo-travellers, business travellers, VFRs and elderly travellers were specifically studied. RESULTS: A total of 3,045 respondents were included in the survey. Travellers to destinations with a high risk for malaria had significantly more accurate risk perceptions (knowledge) than travellers to low-risk destinations. The relative risk for malaria in travellers to high-risk destinations was probably mitigated by higher protection rates against malaria as compared with travellers to low risk destinations. There were no significant differences in intended risk-taking behaviour. Trend analyses showed a significant change over time in attitude towards more risk-avoiding behaviour and towards higher protection rates against malaria in travellers to high-risk destinations. The KAP profile of last-minute travellers substantially increased their relative risk for malaria, which contrasts to the slight increase in relative risk of solo travellers, business travellers and VFRs for malaria. CONCLUSIONS: The results of this sequential cohort survey in Dutch travellers suggest an annual 1.8% increase in protection rates against malaria coinciding with an annual 2.5% decrease in intended risk-seeking behaviour. This improvement may reflect the continuous efforts of travel health advice providers to create awareness and to propagate safe and healthy travel. The KAP profile of last-minute travellers, in particular, substantially increased their relative risk for malaria, underlining the continuous need for personal protective measures and malaria chemoprophylaxis for this risk group.

Trends in knowledge, attitudes, and practices of travel risk groups toward prevention of hepatitis A: results from the Dutch Schiphol Airport survey 2002 to 2009.

BACKGROUND: Previous studies investigating the travelers' knowledge, attitudes, and practices (KAP) profile indicated an important educational need among those traveling to risk destinations. Initiatives to improve such education should target all groups of travelers, including business travelers, those visiting friends and relatives (VFR), and older adult travelers. METHODS: In the years 2002 to 2009, a longitudinal questionnaire-based survey was conducted at the Dutch Schiphol Airport with the aim to study trends in KAP of travel risk groups toward prevention of hepatitis A. The risk groups last-minute travelers, solo travelers, business travelers, travelers VFR, and older adult travelers were specifically studied. RESULTS: A total of 3,045 respondents were included in the survey. Travelers to destinations with a high risk for hepatitis A had significantly less accurate risk perceptions (knowledge) than travelers to low-to-intermediate-risk destinations. The relative risk for hepatitis A in travelers to high-risk destinations was probably mitigated by less intended risk-seeking behavior and by higher protection rates against hepatitis A as compared with travelers to low-to-intermediate-risk destinations. Logistic regression analyses showed that an age >60 years was the only significant determinant for improvement of their knowledge. Trend analyses showed a significant change over time in attitude toward more risk-avoiding behavior and toward higher protection rates against hepatitis A in travelers to high-risk destinations. The KAP profile of the risk groups travelers VFR (irrespective of hepatitis A risk of their destination) and solo as well as last-minute travelers to high-risk destinations substantially increased their relative risk for hepatitis A. CONCLUSIONS: The results of this longitudinal survey in Dutch travelers suggest an annual 5% increase in protection rates against hepatitis A coinciding with an annual 1% decrease in intended risk-seeking behavior. This improvement may reflect the continuous efforts of travel health advice providers to create awareness and to propagate safe and healthy travel. The KAP profile of travelers visiting friends and relatives (VFR) and solo as well as last-minute travelers to high-risk destinations substantially increased their relative risk for hepatitis A. These risk groups should be candidates for targeted interventions.

Local or systemic treatment for New World cutaneous leishmaniasis? Re-evaluating the evidence for the risk of mucosal leishmaniasis.

This review addresses the question of whether the risk of developing mucosal leishmaniasis (ML) warrants systemic treatment in all patients with New World cutaneous leishmaniasis (CL) or whether local treatment might be an acceptable alternative. The risk of patients with New World CL developing ML after the initial infection has been the main argument for systemic treatment. However, this statement needs re-evaluation and consideration of all the available data. The putative benefit of preventing ML should outweigh the toxicity of systemic antileishmanial therapy. To assess the need for and risk of systemic treatment the following factors were reviewed: the incidence and prevalence of ML in endemic populations and in travellers; the severity of mucosal lesions; the efficacy of current options to treat ML; the toxicity and, to a lesser extent, the costs of systemic treatment; the risk of developing ML after local treatment; and the strengths and limitations of current estimates of the risk of developing ML in different situations. Local treatment might be considered as a valuable treatment option for travellers suffering from New World CL, provided that there are no risk factors for developing ML such as multiple lesions, big lesions (>4 cm(2)), localisation of the lesion on the head or neck, immunosuppression or acquisition of infection in the high Andean countries, notably Bolivia.

Dynamics of parasite clearance in cutaneous leishmaniasis patients treated with miltefosine.

Parasite loads were quantified in repeated skin biopsies from lesions of 2 patients with Old-World cutaneous leishmaniasis (CL) caused by Leishmania major and L. infantum during and after treatment with miltefosine. Miltefosine induced a rapid therapeutic effect on both infections with an initial decline of parasites of ∼1 log/week for the L. major infection. These observations illustrate the usability of quantifying parasite loads in skin lesions as a pharmacodynamic measure and quantitative descriptor of drug effect for CL supporting clinical assessment.

A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria.

BACKGROUND: Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. METHODS: In this study the Binax NOW Malaria Test, an easy-to-perform rapid diagnostic test, with Histidine Rich Protein-2 (HRP-2) and aldolase as diagnostic markers, was used for semi-quantitative assessment of parasitaemia of P. falciparum. RESULTS: In 257 patients with imported P. falciparum malaria, reactivity of aldolase increased with higher parasitaemia. In all patients with a parasitaemia above 50,000 asexual parasites/µl (> 1%) co-reactivity of HRP-2 and aldolase was observed. Absence of aldolase reactivity in the presence of HRP-2 was a reliable predictive marker to exclude high (> 1%) parasitaemia in P. falciparum malaria. CONCLUSIONS: Assessment of HRP-2 and aldolase co-reactivity can be of help in clinical decision making in the acute care setting of returning travellers suspected of having malaria.

The potential of molecular diagnosis of cutaneous ectopic schistosomiasis.

A 28-year-old woman presented with extensive erythematous lesions on her back after visiting Malawi. Skin biopsies showed ova, which could belong to Schistosoma spp. Sequencing of the Schistosoma 28S rRNA gene, extracted and amplified from paraffin biopsies, identified DNA of Schistosoma haematobium. Cutaneous ectopic schistosomiasis can present with extensive lesions and should be considered in the differential diagnosis of skin lesions in returning travelers. Microscopy and serology are the classical methods to obtain a diagnosis. Alternatively, molecular methods can be a valuable new tool for diagnosis and species determination.

Pharmacokinetics of miltefosine in Old World cutaneous leishmaniasis patients.

The pharmacokinetics of miltefosine in leishmaniasis patients are, to a great extent, unknown. We examined and characterized the pharmacokinetics of miltefosine in a group of patients with Old World (Leishmania major) cutaneous leishmaniasis. Miltefosine plasma concentrations were determined in samples taken during and up to 5 months after the end of treatment from 31 Dutch military personnel who contracted cutaneous leishmaniasis in Afghanistan and were treated with 150 mg miltefosine/day for 28 days. Samples were analyzed with a validated liquid chromatography-tandem mass spectrometry assay with a lower limit of quantification (LLOQ) of 4 ng/ml. Population pharmacokinetic modeling was performed with nonlinear mixed-effect modeling, using NONMEM. The pharmacokinetics of miltefosine could best be described by an open two-compartment disposition model, with a first elimination half-life of 7.05 days and a terminal elimination half-life of 30.9 days. The median concentration in the last week of treatment (days 22 to 28) was 30,800 ng/ml. The maximum duration of follow-up was 202 days after the start of treatment. All analyzed samples contained a concentration above the LLOQ. Miltefosine is eliminated from the body much slower than previously thought and is therefore still detectable in human plasma samples taken 5 to 6 months after the end of treatment. The presence of subtherapeutic miltefosine concentrations in the blood beyond 5 months after treatment might contribute to the selection of resistant parasites, and moreover, the measures for preventing the teratogenic risks of miltefosine treatment should be reconsidered.

Epidemiology of hepatitis B infection among expatriates in Nigeria.

Adult expatriates in countries where hepatitis B virus (HBV) is highly endemic have an increased risk of HBV infection, but little is known about risks to their children or about patterns of spread. The epidemiology of HBV infection was studied among 124 unvaccinated Dutch missionaries and family members who lived in a rural area of Nigeria. Antibodies to hepatitis B core antigen were found in 5 (9.8%) of 51 adults (incidence rate, 1.7 per 1000 person-months at risk [PMAR]) and 9 (12.3%) of 73 children (incidence rate, 2.8 per 1000 PMAR). Vertical transmission of HBV was a likely source of infection in 1 child and was a possible source of infection in 2 others. The prevalence of HBV infection showed strong family clustering (P<.0001), was associated with a history of temporary adoption of Nigerian children (P=.004), and increased with both the number of adoptive children (P=.009) and the total time that these children had stayed in the family (P=.036). Horizontal transmission from adoptive Nigerian children probably played an important role in the spread of HBV infection in this expatriate community.