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Biomedical subjects

Y Le Fichoux

Publications and source records attributed to Y Le Fichoux.

At least 37 records · Page 2Linked to original sources

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.

AIDS-Related Opportunistic Infections↗

HIV and Leishmania coinfection: a review of 91 cases with focus on atypical locations of Leishmania.

A retrospective study was conducted in France in 1998 to determine the clinical features of visceral leishmaniasis (VL) in 91 patients infected cocomitantly with human immunodeficiency virus. Our data suggest that the clinical manifestations of VL may be influenced by the immunological status, with atypical locations of Leishmania amastigotes more frequently found in severely immunocompromised patients. In such patients, the involvement of atypical locations may lead to the discovery of VL.

AIDS-Related Opportunistic Infections↗

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.

AIDS-Related Opportunistic Infections↗

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.

Administration, Cutaneous↗

Short- and long-term efficacy of hexadecylphosphocholine against established Leishmania infantum infection in BALB/c mice.

In the immunocompetent host, visceral leishmaniasis (VL) is a fatal disease if untreated. In immunosuppressed patients, VL is an opportunistic infection for which there is no effective treatment for relapses. Here we report on the long-term activity of orally administered hexadecylphosphocholine (HDPC) against established Leishmania infantum infection in BALB/c mice. HDPC is a synthetic phospholipid with antiproliferative properties that has been extensively studied for its cancerostatic activity. Its short-term leishmanicidal effects in mice recently infected with viscerotropic Leishmania species have been previously reported. First, we show that 5 days of oral therapy with HDPC (20 mg/kg of body weight/day) led to amastigote suppression in the liver and the spleen of 94 and 78%, respectively (versus 85 and 55% suppression by meglumine antimonate in the liver and spleen, respectively), in mice infected 6 weeks before treatment and examined 3 days after the end of treatment. These results demonstrate the short-term efficacy of HDPC against an established Leishmania infection. Next, the long-term efficacy of HDPC was examined. In HDPC-treated mice both the hepatic and splenic amastigote loads were significantly reduced (at least 89%) 10, 31, and 52 days after the end of the treatment. In the treated mice, the increase of the splenic load was significantly slower than that in the untreated mice, demonstrating that the HDPC-exerted inhibition of Leishmania growth persisted for at least 7 to 8 weeks. Orally administered HDPC--the safe doses and side effects of which are at least partially known--appears to be a promising candidate for the treatment of VL.

Animals↗

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.

Aedes↗

[Localized cutaneous leishmaniasis due to Leishmania infantum MON-1 contracted in northern Algeria].

Classically, the agent of the sporadic skin leishmaniasis in Northern Algeria is Leishmania infantum MON-24. This paper reports the first documented observation of localized cutaneous leishmaniasis due to Leishmania infantum zymodeme MON-1 in Northern Algeria. The interest of using the Western blot serological analysis to guide the diagnosis and the usefulness of the hamster inoculation to isolate Leishmania from pauciparasitized lesion is demonstrated.

Algeria↗

[Endemic subcutaneous Dirofilaria repens filariasis in Southern France].

BACKGROUND: Human dirofilariosis is endemic in southern France. The causal agent is Dirofilaria repens transmitted to man by mosquitos. The human organism is an accidental host while the dog is the reservoir. Approximately 60 cases have been reported in France, mainly in southern continental areas and Corsica. Most cases involve subcutaneous and occular manifestations. CASE REPORT: A 47-year old woman living in the Var department in southern france consulted for a subcutaneous nodule with the aspect of an epidermoid cyst. At incision, the nodule was found to contain a helminth found at parasite examination to be Dirofilaria repens. DISCUSSION: The prevalence of endemic subcutaneous dirofilariosis is probably underestimated as the clinical expression is non-specific and spontaneous cure is common. The diagnosis of epidermoid cyst is frequently suggested. History taking does not reveal travel to intertropical areas. The helminth is discovered when the nodule is opened, also providing successful cure.

Diagnosis, Differential↗

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.

Animals↗

In vitro antifungal resistance of oral Candida albicans strains in non-AIDS patients.

Some cases of oral candidosis are refractory to antifungal treatment. This might be related to development of resistant Candida strains, but susceptibility testing is not standardized and not routinely available, and information related to this problem is scarce in non-AIDS patients. In this study, the in vitro antifungal resistance of oral Candida albicans strains was evaluated. The strains were obtained from a cohort of 72 HIV-negative patients with oral yeast carriage and clinical complaint. Laboratory identification revealed C. albicans in 93% of cases. None of these oral C. albicans isolates showed in vitro resistance to polyenes, but they showed varying resistance levels to fluorocytosine and azoles. This study confirms the usefulness of standardizing susceptibility testing so that it could be routinely available and of realizing a mycological diagnosis including an antifungigram when oral candidosis is suspected, whenever antifungal treatment with azoles is planned.

Antifungal Agents↗

Progression of visceral leishmaniasis due to Leishmania infantum in BALB/c mice is markedly slowed by prior infection with Trichinella spiralis.

We investigated in BALB/c mice the influence of the immunological environment created by the nematode Trichinella spiralis on the course of visceral leishmaniasis due to Leishmania infantum. On the day of Leishmania inoculation (day 0), mice, T. spiralis infected 7 days earlier, presented increased gamma interferon (IFN-gamma), interleukin-4 (IL-4), and IL-5 mRNA levels locally and systemically and increased the potential of spleen cells to synthesize IFN-gamma and IL-4 after activation in vitro. Eighteen days after Leishmania inoculation (day 18), corresponding to the acute phase of leishmaniasis, the hepatic amastigote burden in mice coinfected with L. infantum and T. spiralis (LT mice) was significantly lower (P < 0.001) than that in mice infected with L. infantum only (L mice). IFN-gamma and IL-4 mRNAs were overexpressed in livers of LT and L mice. On day 70, corresponding to the chronic phase, the splenic amastigote load was significantly lower (P = 0.004) in LT mice than it was in L mice. Splenic IFN-gamma transcripts were overexpressed in both L and LT mice. After Leishmania-specific in vitro stimulation, cytokine production was enhanced in both groups, but spleen cells from L mice produced significantly more IFN-gamma than did spleen cells from LT mice. Our data (i) generalize previous results indicating the lack of a clear-cut correlation between the outcome of murine visceral leishmaniasis and the type of cytokine pattern and (ii) demonstrate that in LT mice, leishmaniasis takes a markedly milder course than it does in L mice, providing information on the potential consequences of coinfection in a mammalian host.

Animals↗