[Mediterranean leishmaniasis caused by Leishmania infantum. Update on the utility of the IT-Leish and ID-Pagia leishmaniasis tests]. / La leishmaniose méditerranéenne due a Leishmania infantum Mise au point--intérêts des tests de diagnostic rapide: IT-Leish et ID-Pagia leishmaniasis.

The purpose of this article is to update information about Mediterranean leishmaniasis caused by Leishmania infantum in man and about the canine reservoir. Special emphasis is placed on laboratory diagnosis tests for Mediterranean visceral leishmaniasis (MVL) in humans. In addition two rapid diagnostic tests for human leishmaniasis are compared based on indirect immunofluorescence and Western blot. Findings show that the overall sensitivity of the two tests in immunocompetent and immunodepressed patients ranged from 54% to 97%, a specificity of 97%, with positive predictive value ranging from 75% to 97% and a negative predictive value of around 95%. For diagnosis of cutaneous leishmaniasis, positivity of these tests in one case out of 2 underscores the predictive value of a positive test.

Human trichinellosis due to Trichinella britovi in southern France after consumption of frozen wild boar meat.

Six patients were infected with Trichinella britovi in southern France following consumption of frozen wild boar meat, which had been frozen at -35 degrees C for 7 days. Microscopic examination of a sample of frozen wild boar muscle revealed the presence of rare encapsulated Trichinella larvae, identified as T. britovi. People eating wild boar must follow individual prophylactic rules such as efficient cooking of meat (at least 65 degrees C at the core for 1 minute) as recommended by the International Commission on Trichinellosis, or freezing exceeding four weeks at -20 degrees C.

[Gnathostomiasis: an emerging parasitic disease?]. / La gnathostomose, une parasitose émergente?

INTRODUCTION: Human gnathostomiasis is a parasitic disease caused by the ingestion of foods contaminated with the larvae of various species of Gnathostoma. This zoonosis is currently endemic in Asia and Central America. CASE REPORT: A 46-year-old French woman resident in Vietnam presented with intermittent pruritic swelling of the hand, present for one year, coupled with eosinophilia. The patient's history and serological testing confirmed the suspected diagnosis of gnathostomiasis. A favorable outcome was attained on treatment with albendazole. DISCUSSION: This case, together with several others recently reported in France and Europe, underlines the need to inform travelers and migrants to endemic regions of the risks associated with eating raw or marinated fish.

Visceral leishmaniosis in HIV-positive patients: primary infection, reactivation and latent infection. Impact of the CD4+ T-lymphocyte counts.

OBJECTIVE: To discriminate cases of visceral leishmaniosis (VL) following a primary infection from cases originating in a reactivation of a latent Leishmania infection and to assess the impact of CD4+ T-cell counts on the occurrence of VL in patients with HIV disease. METHODS: We searched by Western blotting for the presence of Leishmania infantum-specific antibodies in the sera of 236 HIV-positive patients. We performed a follow-up of antileishmanial serology and analysed the evolution of the CD4+ T-cell counts for 14 HIV-positive VL patients and for 18 HIV-positive Leishmania-seropositive patients without VL. RESULTS: This study (1) showed that the VL disease/Leishmania infection ratio in HIV-positive individuals is high (1 : 10); (2) discriminated between a primary Leishmania infection (five patients who converted from Leishmania-seronegative to Leishmania-seropositive) and a reactivation of a latent infection (seven patients); (3) showed that HIV-positive individuals with dramatically low CD4+ T-cell counts maintained or generated a specific antileishmanial antibody production; (4) demonstrated that the primary-VL appeared at significantly higher (P = 0.028) CD4+ T-cell levels than the reactivation-VL; (5) documented the existence of HIV-positive Leishmania-seropositive individuals who despite a severe and prolonged immunosuppression did not develop VL (eight of 18). CONCLUSION: Our data stress the utility of the follow-up by Western blotting for an early diagnosis of VL, and therefore an early treatment, for HIV-positive patients living in endemic areas. They suggest that in a latent Leishmania infection supplementary control mechanism(s) might operate in addition to the T-cell-mediated response, and provide a further example of non-appearance of an opportunistic infection despite a severe reduction in CD4+ T cells.

In vivo involvement of polymorphonuclear neutrophils in Leishmania infantum infection.

BACKGROUND: The role of lymphocytes in the specific defence against L. infantum has been well established, but the part played by polynuclear neutrophil (PN) cells in controlling visceral leishmaniasis was much less studied. In this report we examine in vivo the participation of PN in early and late phases of infection by L. infantum. RESULTS: Promastigote phagocytosis and killing occurs very early after infection, as demonstrated by electron microscopy analyses which show in BALB/c mouse spleen, but not in liver, numerous PN harbouring ultrastructurally degraded parasites. It is shown, using mAb RB6-8C5 directed against mature mouse granulocytes, that in chronically infected mice, long-term PN depletion did not enhance parasite counts neither in liver nor in spleen, indicating that these cells are not involved in the late phase of L. infantum infection. In acute stage of infection, in mouse liver, where L. infantum load is initially larger than that in spleen but resolves spontaneously, there was no significant effect of neutrophils depletion. By contrast, early in infection the neutrophil cells crucially contributed to parasite killing in spleen, since PN depletion, performed before and up to 7 days after the parasite inoculation, resulted in a ten-fold increase of parasite burden. CONCLUSIONS: Taken together these data show that neutrophil cells contribute to the early control of the parasite growth in spleen but not in liver and that these cells have no significant effect late in infection in either of these target organs.

The histological spectrum of visceral leishmaniasis caused by Leishmania infantum MON-1 in acquired immune deficiency syndrome.

Visceral leishmaniasis (VL) due to Leishmania infantum is endemic in Southern France and can be considered as an opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Co-infection with Leishmania sp. and human immunodeficiency virus (HIV) is emerging, but pathological findings of leishmaniasis in AIDS have been poorly documented, and scattered case reports have include morphological descriptions. The clinicopathologic analysis of 16 patients with HIV and VL were evaluated. The clinical presentation was characteristic of VL, with fever, hepatosplenomegaly, and pancytopenia in 6 patients, and the diagnosis was confirmed by finding amastigotes of Leishmania sp. in bone marrow smears and biopsy specimens. In 4 patients, the initial diagnosis of VL was made fortuitously in gastrointestinal biopsies performed systematically (3 patients) or in case of diarrhea (1 patient). In one duodenal biopsy, Leishmania sp. and Mycobacteria sp. were associated. Liver biopsy allowed the diagnosis of VL in 3 cases. Autopsy was performed in 9 patients, showing a disseminated leishmaniasis with very unusual localizations (adrenal and heart) in 2 cases. Cutaneous leishmaniasis involvement was noted before (4 patients), at the same time (2 patient), or after (1 patient) the diagnosis of VL. Inflammatory infiltrates noted with Leishmania sp. infection were made by CD68 macrophages with (8 patients) or without (8 patients) associated CD8 positive lymphocytes. Immunoperoxidase study using polyclonal anti-Leishmania sp. antibodies contributed to the diagnosis in all cases. Electron microscopy of 2 digestive biopsy specimens showed the ultrastructural characteristics of Leishmania sp. amastigotes. The zymodeme MON-1 of L infantum was identified by isoenzyme electrophoresis in all patients. The mean of CD4 counts was 37/mm3 at the time of diagnosis, and the mean duration before the death was 8 months. As shown in this study, VL in AIDS can be diagnosed in gastrointestinal or liver biopsies. Diagnosis of VL was made when the CD4 count was very low and was correlated with a poor prognosis.

Cutaneous leishmaniasis due to Leishmania infantum. Case reports and literature review.

BACKGROUND: Leishmania infantum recently has been identified as a possible agent of cutaneous leishmaniasis (CL). This species has been isolated from cutaneous lesions of patients from the Mediterranean Basin. However, little is known about the clinical, biological, or therapeutic features of this newly recognized CL. OBSERVATIONS: Six patients aged 9 months to 85 years in southeastern France were found to have autochthonous leishmaniasis. Parasitological identification showed that the agent was L infantum, zymodemes Montpellier-1 for 2 patients and Montpellier-24 for 1 patient. Five patients who underwent testing with a Western blot assay were found to have antibodies against 4 antigens with molecular masses of 18, 21, 23, and 31 kd. Five patients were successfully treated with local injections of N-methylglucamine, and 1 patient was successfully treated with topical paromomycin sulfate. No patient had visceral disease at diagnosis or after follow-up. CONCLUSIONS: Recent data provide increasing evidence that L infantum is an important agent of CL. In southwestern Europe, this species is the only agent that has long been identified from autochthonous CL. Leishmania infantum should be considered an agent of CL in areas in which visceral leishmaniasis is endemic. Western blot assay could be a useful test for the diagnosis, but precise parasitological identification is important to having a better knowledge of the disease. The relationships between CL and the visceral disease have to be explored.

Human visceral leishmaniasis in Alpes-Maritimes, France: epidemiological characteristics for the period 1985-1992.

In 8 years (1985-1992), 65 cases of human visceral leishmaniasis (HVL) have been diagnosed in the department of Alpes-Maritimes, France, 56 of them having been infected locally. The annual frequency has increased from 3 cases in 1985 to 15 cases in 1992. There is a low rate of paediatric cases (29%) and a predominance of males among adult cases (85%). Since 1986, 19 cases of co-infection with Leishmania and human immunodeficiency virus 1 have been reported, corresponding to 40% of adult cases and to 30% of the total cases. The frequency of co-infections is stable at about 3 per annum. Isoenzymatic identification of the strains isolated from patients confirmed Leishmania infantum zymodeme MON-1 as responsible for most if not all HVL in the department of Alpes-Maritimes; 42 of the 44 strains isolated belonged to that zymodeme.

Leishmanin reaction in the human population of a highly endemic focus of canine leishmaniasis in Alpes-Maritimes, France.

The reactivity of the human population was studied in the village of l'Abadie, a suburban focus of canine leishmaniasis (17% of dogs seropositive in 1985); 237 subjects were tested in 1989. The total positive rate was 30%. A higher proportion of positive skin tests was obtained in the 61-70 years age group (62%) than in the younger groups. The proportion of positive tests also increased with the duration of living in this locality (22% for less than 5 years; 66% for more than 21 years). These data confirm the continuing occurrence of transmission of leishmaniasis to human beings in this focus.

Use of the leishmanin skin test and western blot analysis for epidemiological studies in visceral leishmaniasis areas: experience in a highly endemic focus in Alpes-Maritimes (France).

Fifty unselected subjects living in Alpes-Maritimes, France, a high risk area for visceral leishmaniasis due to Leishmania infantum, were examined simultaneously by the leishmanin skin test and the Western blot technique in 1993; 32% and 38%, respectively, gave a positive reaction. The concordance of the 2 methods was 82%. Thus, in this high risk area, a large proportion of inhabitants had been exposed to the parasite. The use of these 2 tests should permit the detection of potential cases of reactivated leishmaniasis in prospective follow-up investigations.

Detection by Western blot of four antigens characterizing acute clinical leishmaniasis due to Leishmania infantum.

Western blot analysis of sera from 32 patients with acute clinical leishmaniasis due to Leishmania infantum showed the simultaneous presence of antibodies against 4 antigens with molecular masses of 18, 21, 23, 31 kDa. The simultaneous presence of these 4 antigens was specific to the clinical disease and it was not detected in 47 sera from asymptomatic individuals living in the leishmaniasis endemic area of Alpes-Maritimes (southern France) or in 37 sera from patients with other protozoan infections.

[Pruriginous dermatitis due to Pyemotes zwoelferi Krczal, 1963. About several cases in the Alpes-Maritimes (France) (author's transl)]. / Dermatite prurigineuse due à Pyemotes zwoelferi Krczal, 1963. a propos de plusieurs cas dans les alpes-maritimes.

In September 1978, people having had contacts in the neighbouring of Nice with an everlasting flower package (Helichrysium angustifolium) from Jugoslavia, complained of prurigo. The erythematous lesions with a central vesicle regressed during the second week but did not fade out until the third week. Among the everlasting flowers were found numerous and swiftly mowing fasting females of Pyemotes zwoelferi. Those mites are usually parasitic on phytopathogenic insects. Their aggressiveness against human beings is related to sudden development of their population and, also to the specific toxicity of their venom. Systematically P. zwoelferi comes in the same species group as P. tritici.

[A case of external ophthalmomyiasis by Oestrus ovis, Linné, 1758 caught on the Nice beach (author's transl)]. / Un cas d'ophtalmomyiase externe à oestrus ovis, linné, 1758 contractée sur la plage de nice.

A case of external ophthalmomyiasis by Oestrus ovis is recorded from Provence-Côte-d'Azur (France). The patient has been constaminated on the Nice beach far away from the breeding areas of sheep and goats which are the usual host of this fly. One larva specimen, which was found in the patient's eye, is described and compared to the larva of Rhinoestrus purpureus, another agent of external human ophthalmomyiasis.

Sustained parasite burden in the spleen of Leishmania infantum-infected BALB/c mice is accompanied by expression of MCP-1 transcripts and lack of protection against challenge.

We analyzed differential responses of spleen and liver, major organ targets for viscerotropic Leishmania species, to experimental infection and examined if resistance to challenge was organ-specific. In liver, parasites were spontaneously cleared and iNOS trancripts expression paralleled that of amastigote load. In the spleen, amastigote multiplication was only partly controlled, and iNOS transcripts expression was transient. Total numbers of spleen cells, B cells, and T cells were decreased, while F4/80(+) and Mac1(+) cells were conserved. Expression of splenic MCP-1 transcripts remained constant, indicating its possible contribution to immigration of Leishmania host cells and to sustained parasite load. Spleen cells produced both, Th1- and Th2-type cytokines and Th2-type response was dominant, compatible with the sustained MCP-1 expression. Challenge experiments showed that in contrast to the liver, where initial infection conferred a progressively established immunity, in the spleen there was no induced protection against reinfection. Organ-specific resistance against challenge could be important for designing antileishmanial vaccines.

Prolonged administration of dexamethasone induces limited reactivation of visceral leishmaniasis in chronically infected BALB/c mice.

Leishmania parasites persist in their vertebrate host after the treatment-induced clinical cure and in the asymptomatic infection. They confer resistance to reinfection but represent a risk of occurrence of acute leishmaniosis in immunosuppressed conditions. We examined the effects of prolonged dexamethasone administration on a chronic Leishmania infantum infection. Splenic T cell populations from the long-term-infected BALB/c mice were reduced by 55%, whereas those from uninfected controls were depleted by 85%. The ability of the remaining spleen cells to produce IL-2, IFN-gamma, IL-4 and TNF-alpha after in vitro specific stimulation decreased twofold, and the specific anti-leishmanial antibodies declined 3- to 5-fold. Liver, spleen and bone marrow are the main L. infantum targets in natural and experimental infections. Three-fold increase of amastigote burden was evidenced in the spleen, after dexamethasone administration was prolonged for over 2 months. No reactivation of Leishmania proliferation was disclosed in the liver and bone marrow. These results show a decreased sensitivity of splenic T cells to dexamethasone in a chronic Leishmania infection and a distinct response of the Leishmania-infected target organs to the dexamethasone-induced immunosuppression.

Medical treatment of a pacemaker endocarditis due to Candida albicans and to Candida glabrata.

We describe a case of pacemaker infection due to two fungal species: Candida albicans and C. glabrata. Transthoracic echocardiography showed a large vegetation on the intraventricular wires. Because of severe underlying diseases, surgery was believed to be contraindicated. The patient was treated using high dose of fluconazole, resulting in clinical improvement and negative blood cultures. However, 2 months later, the patient underwent a fatal stroke. At autopsy, a large vegetation was found only all along the wires. Postmortem culture of the infected material was positive for both C. albicans and C. glabrata.

Consensual treatment of plasmodium falciparum malaria does not lead to adequate quinine blood concentrations.

Since 1996, we have a common protocol in the Infectious Diseases Department and the Intensive Care Unit for the administration of quinine in case of Plasmodium falciparum malaria. Patients were classified as uncomplicated form of malaria (UFM) or severe form of malaria (SFM) according to WHO criteria, adding parasitemia >5% as a criteria of SFM. Treatment of SFM should consist of a 4 h infusion of 16 mg/kg quinine-base loading dose, followed by 8 mg/kg every 8 h. Patients with UFM receive quinine-base, 8 mg/kg every 8 h. A therapeutic index of 10-15 mg/l was considered adequate. Hypoglycemia and cardiotoxicity were the two main adverse effects of quinine to be investigated. In order to verify that these modalities for quinine administration are associated with adequate quinine blood concentrations, we have reviewed the pharmacological data and the occurrence of adverse effects. Between April 1996 and December 2000, 95 patients were hospitalised: 25 with SFM and 70 with UFM: 78/95 patients (82%) received adequate treatment and 26/95 (28%) of the patients presented an overdosage of quinine. Six severe adverse effects were observed, even in case of adequate quinine administration. Consensual treatment of malaria does not confer adequate quinine blood concentrations, and toxic effects are still common.

Extracerebral toxoplasmosis in the acquired immunodeficiency syndrome (AIDS).

Although Toxoplasma gondii frequently causes lesions of the central nervous system in AIDS, the exact incidence of extracerebral toxoplasmosis in these immunodepressed patients remains difficult to determine. Isolation of the parasite outside the central nervous system is rarely performed ante mortem, and most diagnoses of extracerebral toxoplasmosis are made post mortem. This article describes 23 cases of extracerebral toxoplasmosis diagnosed between 1987 and 1991 in an autopsy series of 170 patients infected with the human immunodeficiency virus (HIV). Ante mortem diagnosis of extracerebral involvement was affirmed in 4 of these 23 patients by identification of trophozoites in bronchoalveolar lavage fluid (2 cases), a surgical pulmonary biopsy specimen, and a bladder biopsy. Clinical and paraclinical findings suggested cardiac involvement in 4 other patients. Post mortem examination demonstrated disseminated toxoplasmosis in 18 cases and extracerebral monovisceral involvement in 5 cases. Extracerebral toxoplasmosis was directly responsible for the death of 6 patients. The most frequent extracerebral sites of Toxoplasma gondii involvement were the heart (21/23 cases; 91%), the lungs (14/23 cases; 61%) and the pancreas (6/23 cases; 26%). The tissular consequences of toxoplasmic involvement varied considerably, from formation of pseudocysts or cysts without any surrounding inflammatory reaction to necrotic lesions rich in neutrophilic polynuclear cells containing numerous free parasites. Immunoperoxidase study using antitoxoplasmic antibodies contributed to the diagnosis of 8 extracerebral localizations. Electron microscopy examination of a surgical lung biopsy and myocardial specimens (2 cases) demonstrated the ultrastructural characteristics of Toxoplasma gondii trophozoites.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of a survey to detect the mosquito Aedes albopictus in the French Riviera.

A programme of surveillance was initiated in 1992, in the French Riviera, to detect a possible introduction of Aedes albopictus from Italy and to prevent nuisances caused by mosquitoes in the touristic localities of the Côte d'Azur. In five years, numerous mosquito breeding places have been located. Nine species have been collected: Anopheles claviger, An. plumbeus, Aedes geniculatus, Ae. vittatus, Culex hortensis, Cx. impudicus, Cx. pipiens, Culiseta fumipennis, Cs. longiareolata but no Ae. albopictus was found. Nuisances were mainly due to hypogean populations of Cx. pipiens. Breeding places in urban sites have been controlled or suppressed. The discovery of an important larval population of An. plumbeus in an urban area might further stress the importance of this species already suspected to transmit indigenous malaria in cities.