Imported leishmaniasis in the Netherlands from 2005 to 2012: epidemiology, diagnostic techniques and sequence-based species typing from 195 patients.

Leishmaniasis is an imported disease in the Netherlands. We report data for the period between 2005 and 2012, on clinical presentation, country where leishmaniasis was acquired, and causative species, for 195 civilian and military patients who had travelled abroad. Most patients were affected by cutaneous leishmaniasis (CL) (n=185 patients), while visceral leishmaniasis (VL) (n=8 patients) and mucocutaneous leishmaniasis (n=2 patients) were less frequently observed. All VL patients had been infected in Europe. CL was mainly acquired in Afghanistan, Surinam, Morocco and Spain. The majority of CL patients consisted of military personnel (55%, 102/185), 78 of whom had been infected during an outbreak in Afghanistan. Parasitological diagnosis was made by a combination of polymerase chain reaction (PCR), microscopy and culture. Compared to a standard of parasitological proof by any method other than the one under consideration, sensitivities of the individual methods ranged from 73% to 98%. Microscopy was least sensitive, but is fast and cheap. Mini-exon repeat PCR combines high sensitivity and specificity, and allows differentiation between species by sequencing of the PCR product. Eight different species or species complexes were identified, allowing species-specific therapy. Four patients proved infected with Leishmania naiffi, a hitherto rarely described cause of leishmaniasis. In comparison to previous decennia, an increase in cutaneous leishmaniasis was observed in our hospital, both in civilian and military patients who had travelled abroad. This calls for increased awareness among clinicians, availability of diagnostic tests and species-specific treatment guidelines in non-endemic countries.

Rabies vaccinations: are abbreviated intradermal schedules the future?

Rabies is a deadly disease, and current preexposure vaccination schedules are lengthy and expensive. We identified nine studies investigating abbreviated schedules. Although initial responses were lower, accelerated adequate immune responses were elicited after booster vaccinations. Lower-dose (and therefore cheaper) vaccination schedules may constitute a valid alternative to current vaccination schedules.

The tropics and the crime they did not commit.

Travellers to tropical destinations who seek medical attention after returning to their home country often present with fever, frequently as a result of an imported infectious disease. For this reason, clinicians initially focus on an infectious cause when a clear relationship in time exists between travel and disease onset. We present a case of a patient, who developed fever 2 weeks after his return from Ghana and who was finally diagnosed with an auto-immune disease: arteritis of the large arteries. This case illustrates that broad differential diagnostic thinking is paramount in the assessment of returned travellers.

Cutaneous leishmaniasis in three Dutch military cohorts following jungle training in Belize.

Skin lesions occur frequently in travelers to tropical countries. Military personnel acquire skin lesions regularly during jungle training as did Dutch troops who trained in the jungle of Belize in 1998, 2004 and 2009, in an area endemic for cutaneous leishmaniasis. Demographic and clinical data were collected retrospectively. Diagnostic investigations for cutaneous leishmaniasis included Giemsa stain, culture, PCR and NASBA and histopathology of biopsies. Treatment of leishmaniasis was with sodium stibogluconate, given intravenously or intralesionally, the latter with cryotherapy. In 1998 and 2004 cutaneous leishmaniasis due to Leishmania braziliensis and Leishmania mexicana infection was diagnosed in 25 persons out of 99 (attack rate 25.2%) and 14 persons out of 80 (attack rate 17.5%) respectively. In 2009 cutaneous leishmaniasis was not acquired. Skin problems were common during and after jungle training. Cutaneous leishmaniasis was important in the first two cohorts but not observed in the third cohort. Factors that could have played a role in the absence of cutaneous leishmaniasis in the third cohort include variability in transmission and availability of better preventive measures and adherence to these. Sodium stibogluconate treatment, intralesional or intravenous, was effective.

Miltefosine treatment of Leishmania major infection: an observational study involving Dutch military personnel returning from northern Afghanistan.

In a retrospective, observational study involving 34 patients with Leishmania major infection, 31 of whom had experienced unsuccessful treatment with intralesional antimony (ilSb(v)), miltefosine proved effective. Thirty patients experienced cure after receipt of miltefosine, 3 after receipt of additional ilSb(v), and 1 after 28 daily intravenous injections of antimony. Temporary diminution of ejaculate volume was reported by 21 patients.

Treatment assessment by monitoring parasite load in skin biopsies from patients with cutaneous leishmaniasis, using quantitative nucleic acid sequence-based amplification.

BACKGROUND: Current diagnostic methods for cutaneous leishmaniasis (CL) have low sensitivity or are not useful for treatment follow-up. We previously described the quantitative nucleic acid sequence-based amplification (QT-NASBA) method as a sensitive and specific assay for detection and quantification of Leishmania parasites in skin biopsies. This assay could be a valuable instrument for monitoring response to treatment of CL and identifying treatment failures at an early stage. AIM: QT-NASBA results of skin biopsies at the end and 6 weeks after treatment from patients with proven CL on various treatment regimens were compared with clinical outcome. METHODS: The QT-NASBA assay measured the parasite load in skin biopsies before, at the end and 6 weeks after treatment. The results were compared with treatment outcome (clinical cure, delayed healing response or treatment failure) up to 6 months after treatment. RESULTS: In total, 137 skin biopsies were obtained from 53 patients. A positive QT-NASBA result 6 weeks after treatment was significantly associated with treatment failure/delayed healing up to 6 months (P < 0.001). The positive predictive value (PPV) was 100% and the negative predictive value (NPV) was 92% (95% CI 82-100%). QT-NASBA results at the end of treatment and clinical outcome showed a less significant association (P < 0.05), with a PPV of 46% (95% CI 16-75% and an NPV of 89% (95% CI 79-99%). CONCLUSIONS: The QT-NASBA assay is a useful instrument to monitor parasite load in skin biopsies of patients with CL 6 weeks after treatment and can help to predict clinical outcome.

Changing pattern of imported cutaneous leishmaniasis in the Netherlands.

Cutaneous leishmaniasis (CL) in western countries seems to be appearing more frequently. Our aim was to determine if there has been a shift in countries where CL is acquired and whether the incidence has changed, and to assess current diagnostic procedures and treatment modalities. In a retrospective study medical records of patients with the diagnosis of CL at the Departments of Tropical Dermatology and Tropical Medicine, Academic Medical Center, Amsterdam, the Netherlands, from 1990 to 2000 were analysed. CL was diagnosed in 78 patients. The majority was acquired in Belize, Surinam, French Guyana and Bolivia. Giemsa stains were positive for the parasite in impression smears from 43% and in biopsies from 71%. Seventy-eight per cent of cases were culture-positive and 89% were PCR-positive. Sixty-two patients were treated systemically: pentavalent antimony (32), pentamidine isetionate (11), itraconazole (19), and 13 locally, the majority with a combination of cryosurgery and intralesional pentavalent antimony. Imported CL is becoming more frequent, with South and Middle American countries being important sources of infection. Multiple tests, of which PCR is the most sensitive, are required to confirm the diagnosis. Systemic treatment was given to the majority of the patients.

[Three patients with African sleeping sickness following a visit to Tanzania]. / Drie patiënten met Afrikaanse slaapziekte na een bezoek aan Tanzania.

Three Dutch tourists, a man aged 57 and two women aged 55 en 52 years, acquired African trypanosomiasis in the national parks of Tanzania. Two, without central nervous system involvement, were cured after treatment in the Netherlands, albeit one after having suffered a relapse. In the third patient, involvement of the central nervous system was diagnosed in Africa and she was treated with melarsoprol. After an apparently uneventful recovery she was readmitted with cerebral complaints and symptoms. While being treated with melarsoprol she lapsed into coma. She died following repatriation. An epidemic of trypanosomiasis is currently raging through Central Africa. In several western countries, trypanosomiasis has been diagnosed recently in tourists who visited Tanzania.

[Fever and chills due to leptospirosis after travel to Thailand]. / Koorts en koude rillingen na een bezoek aan Thailand, door leptospirose.

Two weeks after rafting on a river in Thailand a Dutch 54-year-old male experienced chills and high fever. While rafting he had wounded his hand. Because of the history (water contact, the wound, high fever with chills), of the findings at examination (fever, conjunctivitis) and of the laboratory findings (leukocytosis, albuminuria, disturbance of liver enzymes), a clinical diagnosis of 'leptospirosis' was made. This was confirmed by serological tests and culturing of Leptospirae from the blood. Leptospirosis is a zoonosis, in man associated with certain occupations, water sports and inundations. The clinical picture varies from a mild febrile disease (sometimes pyrexia of unknown origin) to a severe condition with kidney and liver failure, bleeding tendency, lung oedema (Weil's syndrome). In travellers with fever, water contact, leukocytosis and neutrophilia, leptospirosis must be considered and specific diagnostic tests applied.

Tolerance of mefloquine chemoprophylaxis in Dutch military personnel.

From June until October 1993, a battalion of Dutch marines was stationed in Cambodia for a United Nations deployment. In 73 volunteers who used mefloquine as malaria chemoprophylaxis, possible mefloquine-related adverse events were monitored with special emphasis on QT prolongation. All participants started mefloquine chemoprophylaxis with a loading dose (250 mg a day for three days) one week before departure, followed by a weekly dose (250 mg) for approximately 25 weeks. One month before (t - 1) and one (t + 1) and three (t + 3) months after mefloquine prophylaxis was started, an at rest electrocardiogram was made. Frequency, PR-, and QT-intervals were measured; blood samples for liver transaminases, total white blood cell count, and mefloquine concentration were obtained after one and three months. Adverse events such as dizziness, headache, coordination problems, and nausea were spontaneously reported in one (1.4%) and three (4.1%) persons at t + 1 and t + 3, respectively, while specific questioning revealed adverse events in nine (12.3%) and five (6.9%) persons, respectively, at the same time point. Three months after starting chemoprophylaxis, the heart rate at rest and total white blood cell count were lower (P < 0.05), while the QTc-interval was longer and levels of liver transaminases increased (P < 0.05), although both were still within the normal range. There was no extreme prolongation of the QTc-interval or increased levels of liver transaminases that resulted in a need to stop the chemoprophylaxis. No accumulation of mefloquine in the serum occurred, and no relationship was observed between the incidence of adverse events and serum mefloquine concentrations. The incidence of self reported mefloquine-related adverse events was low. In conclusion, mefloquine chemoprophylaxis was safe and well-tolerated in this group.

Long-term malaria chemoprophylaxis with mefloquine in Dutch marines in Cambodia.

Three Dutch marine battalions (n=2289) serving in Western Cambodia during 1992-1993 used mefloquine as weekly malaria chemoprophylaxis. One battalion started with a loading dose. Full compliance with prophylaxis was reported by 86.3%, and possible mefloquine-related adverse events were reported by 30.2%. Sixty-four periods of malaria were diagnosed in 59 marines. During deployment, 31 Plasmodium falciparum and no Plasmodium vivax infections occurred. After return, there were 11 cases of falciparum malaria and 22 of vivax malaria, 16-72 days and 30-540 days, respectively, after stopping prophylaxis. Mefloquine-resistant parasites were isolated from 4 Dutch and 4 Khmer patients. Long-term mefloquine prophylaxis was well tolerated but not totally effective.