Jan Clerinx

Schistosomiasis in travellers and migrants.

Schistosomiasis is a tropical parasitic disease caused by blood-dwelling fluke worms of the genus Schistosoma whose infective stages, the cercariae, are amplified through mollusks acting as intermediate hosts. People are infected when exposed to fresh water containing cercariae that penetrate the skin. There are however considerable differences in intensity of infection and morbidity, depending on the pattern of exposure and the infective species. In travellers, schistosomiasis differs substantially from infection in endemic populations in many aspects: geography, morbidity, treatment and prevention. In migrants, schistosomiasis manifests itself in a way more akin to what is seen in endemic populations. In this paper we will review the specific issues associated with schistosomiasis in travellers and migrants, with emphasis on the acute disease manifestations in non-immune persons, and on neuroschistosomiasis as a potential severe complication. We discuss new trends in diagnosis and treatment with respect to the specific disease stage, and summarize precautionary measures and novel ways to prevent Schistosoma infection in travellers.

Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium

BackgroundIntravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe.MethodsHospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated.ResultsOf the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%). The mean time to 50% parasite clearance (PCT50), 90% and 99% were 4.4 hours (3.9 - 5.2), 14.8 hours (13.0 - 17.2), and 29.5 hours (25.9 - 34.4) respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain.ConclusionsData from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment.Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug.

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.

Recurrence of blackwater fever: triggering of relapses by different antimalarials.

Five cases of blackwater fever (BWF) are described, all of whom had a history of recent quinine therapy. In two cases a second haemolytic crisis was induced by halofantrine, in one case also a third. Increasing frequency of this syndrome with its dramatic clinical presentation is to be expected as imported P. falciparum infection, parasite resistance to chloroquine and the use of quinine and other related antimalarials become more frequent.

Heat-shock protein 70 gene sequencing for Leishmania species typing in European tropical infectious disease clinics

We describe Leishmania species determination on clinical samples on the basis of partial sequencing of the heat-shock protein 70 gene (hsp70), without the need for parasite isolation. The method is especially suited for use in non-endemic infectious disease clinics dealing with relatively few cases on an annual basis, for which no fast high throughput diagnostic tests are needed. We show that the results obtained from this gene are in nearly perfect agreement with those from multilocus enzyme electrophoresis, which is still considered by many clinicians and the World Health Organization (WHO) as the gold standard in Leishmania species typing. Currently, 203 sequences are available that cover the entire hsp70 gene region analysed here, originating from a total of 41 leishmaniasis endemic countries, and representing 15 species and sub-species causing human disease. We also provide a detailed laboratory protocol that includes a step-by-step procedure of the typing methodology, to facilitate implementation in diagnostic laboratories.

A Schistosoma haematobium-Specific Real-Time PCR for Diagnosis of Urogenital Schistosomiasis in Serum Samples of International Travelers and Migrants

Background Diagnosis of urogenital schistosomiasis by microscopy and serological tests may be elusive in travelers due to low egg load and the absence of seroconversion upon arrival. There is need for a more sensitive diagnostic test. Therefore, we developed a real-time PCR targeting the Schistosoma haematobium-specific Dra1 sequence. Methodology/Principal Findings The PCR was evaluated on urine (n = 111), stool (n = 84) and serum samples (n = 135), and one biopsy from travelers and migrants with confirmed or suspected schistosomiasis. PCR revealed a positive result in 7/7 urine samples, 11/11 stool samples and 1/1 biopsy containing S. haematobium eggs as demonstrated by microscopy and in 22/23 serum samples from patients with a parasitological confirmed S. haematobium infection. S. haematobium DNA was additionally detected by PCR in 7 urine, 3 stool and 5 serum samples of patients suspected of having schistosomiasis without egg excretion in urine and feces. None of these suspected patients demonstrated other parasitic infections except one with Blastocystis hominis and Entamoeba cyst in a fecal sample. The PCR was negative in all stool samples containing S. mansoni eggs (n = 21) and in all serum samples of patients with a microscopically confirmed S. mansoni (n = 22), Ascaris lumbricoides (n = 1), Ancylostomidae (n = 1), Strongyloides stercoralis (n = 1) or Trichuris trichuria infection (n = 1). The PCR demonstrated a high specificity, reproducibility and analytical sensitivity (0.5 eggs per gram of feces). Conclusion/Significance The real-time PCR targeting the Dra1 sequence for S. haematobium-specific detection in urine, feces, and particularly serum, is a promising tool to confirm the diagnosis, also during the acute phase of urogenital schistosomiasis.

Schistosoma real-time PCR as diagnostic tool for international travellers and migrants.

Objective  To evaluate the use of a genus‐specific PCR that combines high sensitivity with the detection of different Schistosoma species for diagnosis in international travellers and migrants in comparison to standard microscopy.

Acute schistosomiasis in a cluster of travelers from Rwanda: diagnostic contribution of schistosome DNA detection in serum compared to parasitology and serology.

BACKGROUND Diagnosis of acute schistosomiasis is often elusive in travelers. Serum schistosome DNA detection is a promising new diagnostic tool. Its performance is compared with current diagnostic procedures in a cluster of travelers recently infected in Rwanda. METHODS Recent infection with schistosomiasis was suspected in 13 Belgian children and adults, within 2 months after swimming in the Muhazi Lake, Rwanda. All were subjected to clinical examination, eosinophil count, feces parasite detection, schistosome antibody tests [enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition assay (HAI)], and schistosome DNA detection in serum by real-time polymerase chain reaction. RESULTS All 13 patients, between 6 and 29 years old, had a high eosinophil count (median 2,120 µL(-1) ; range 1,150-14,270). Seven of nine persons exposed for the first time developed symptoms compatible with acute schistosomiasis. Eggs of Schistosoma mansoni were found in a concentrated feces sample of 9/13 (69%), with low egg counts (median 20 eggs per gram; range 10-120). Antischistosome antibodies (ELISA and/or HAI) were present in serum of 10/13 (77%) patients. Combining schistosome antibody tests and fecal microscopy demonstrated schistosomiasis in 11/13 (85%) patients. Schistosome-specific DNA was isolated in all 13 (100%) serum samples. CONCLUSION In this cluster of travelers with acute schistosomiasis, schistosome DNA detection in serum was able to confirm infection in all exposed persons. It clearly outperformed antibody tests and microscopic parasite detection methods as a qualitative diagnostic test.

Therapy of uncomplicated falciparum malaria in Europe: MALTHER – a prospective observational multicentre study

BackgroundMalaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe.MethodsA prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine.ResultsBetween December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p < 0.001), and hospitalization rates (p = 0.0066) and durations (p = 0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group.ConclusionsThis study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.

Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study

Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria.