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Martin Danis

Publications and source records attributed to Martin Danis.

18 recordsLinked to original sources
PubMed2006

Identification of new antimalarial drugs by linear discriminant analysis and topological virtual screening.

OBJECTIVES: A quantitative structure-activity relationship study using a database of 395 compounds previously tested against chloroquine-susceptible strains of the blood stages of Plasmodium falciparum to predict new in vitro antimalarial drugs has been developed. METHODS: Topological indices were used as structural descriptors and were related to antimalarial activity by using linear discriminant analysis (LDA) and multilinear regression (MLR). Two discriminant equations were obtained (FD1 and FD2), which allowed us to carry out successful classification of 90% and 80% of compounds, respectively. The IC50 values of the compounds were introduced to get an MLR equation model suitable to predict their in vitro activities. RESULTS: Using this model, a set of 27 drugs against a chloroquine-susceptible clone (3D7) of P. falciparum have been selected and evaluated in vitro. Among these drugs are monensin, nigericin, vincristine, vindesine, ethylhydrocupreine and salinomycin with in vitro IC50s at nanomolar concentrations (0.3, 0.4, 2, 6, 26 and 188 nM, respectively). Other compounds such as hycanthone, amsacrine, aphidicolin, bepridil, amiodarone, ranolazine and triclocarban showed in vitro IC50 values below 5 microM in the mathematical model. CONCLUSIONS: These results demonstrate the usefulness of the approach for the selection and design of new lead drugs active against P. falciparum.

Animals↗
PubMed2006

Efficacy of praziquantel during the incubation and invasive phase of Schistosoma haematobium schistosomiasis in 18 travelers.

The efficacy of praziquantel started during the incubation period of schistosomiasis has not been studied. Eighteen tourists were infected by Schistosoma haematobium during summer 2003 after bathing once in the same cascade in Mali. We observed the efficacy of praziquantel given at different phases. They received praziquantel at the first consultation, from Days 10 to 15 after exposure in eight asymptomatic patients (Group 1), from Days 28 to 40 in 4 asymptomatic patients (Group 2), and from Days 20 to 39 in 6 patients with acute schistosomiasis (Group 3). All Group 1 patients developed acute schistosomiasis, compared with none of the Group 2 patients (P < 0.004). Among the 10 patients treated during the acute phase, clinical status deteriorated in four cases. Seventeen of the 18 patients developed chronic schistosomiasis. Early praziquantel treatment was thus less effective than later treatment in preventing acute schistosomiasis, while neither treatment effectively prevented chronic schistosomiasis.

Adolescent↗
PubMed2005

[Malaria chemoprophylaxis in 2005: new policy, new drugs].

For a traveller visiting highly endemic areas for malaria (mainly sub-Saharan Africa), the use of a chemoprophylaxis has to be considered as mandatory in addition to exposure prophylaxis measures (including in migrants largely over-represented among returning travellers with imported malaria). The choice of the appropriate drug depends mainly on the visited area with regard to the level of resistance to chloroquine. Due to the spread of resistance, 7 countries along the West African coast between Senegal and Côte d'Ivoire moved in 2005 from zone 2 to zone 3 (according to the French classification). Recently available and recommanded in zones 2 and 3, the atovaquone+proguanil combination appears to be of great interest due to a good tolerance and an intake limited to the 7 days following return. Alternatively to mefloquine or atovaquone+proguanil, the well tolerated and cheap doxycycline is a good choice but due to its short half life a full compliance is mandatory. In case of fever, even if a chemoprophylaxis is taken, malaria can develop, sometimes with atypical presentations, and has to be systematically considered.

Antimalarials↗
PubMed2005

Detection of Aspergillus galactomannan antigenemia to determine biological and clinical implications of beta-lactam treatments.

Detection of Aspergillus galactomannan (GM) in serum with the Platelia Aspergillus enzyme immunoassay (EIA) is useful for diagnosing invasive aspergillosis. From May 2003 to November 2004, 65 patients who did not develop aspergillosis had at least two positive sera while receiving a beta-lactam treatment (GM index [GMI], >or=0.5). Of the 69 treatment episodes scored, 41 consisted of a beta-lactam other than piperacillin-tazobactam (n=29), namely, amoxicillin-clavulanate (n=25), amoxicillin (n=10), ampicillin (n=3), or phenoxymethylpenicillin (n=2). In all cases, antigenemia became negative 24 h to 120 h upon stopping the antibiotic. Monitoring of 35 patients, including 26 with hematological malignancies, revealed three antigenemia kinetic patterns: each was observed with any drug regimen and consisted of a persistent GMI of >2.0 (65.7%), >0.5, and <or=1.5 (25.7%) or a variable GMI (14.3%) from the onset of antibiotic therapy. All available drug batches given to 26 patients cross-reacted with the EIA. Galactomannan titration in batches failed to predict the GM titers in the five patients studied at cumulative doses of ampicillin or amoxicillin-clavulanate, regardless of the time lapse between serum sampling and infusion period. Our results show that beta-lactams other than piperacillin-tazobactam may lead to false presumption of aspergillosis. The resulting kinetic patterns of GM antigenemia are variable, and sampling serum prior to the next beta-lactam dose may not decrease GMI below the threshold. Consequently, testing of suspected antibiotic batches remains the only indicator of possible false EIA positivity.

Antigens, Fungal↗
PubMed2004

[Gnathostomosis, an exotic disease increasingly imported into Western countries].

AN INCIDENTAL HELMITHIASIS IN MAN: Gnathostomiasis is an helminthic disease of animals due to a nematode belonging to the gender Gnathostoma. This gender includes many species, the most frequent being Gnathostoma spinigerum. Man is an incidental host. Human gnathostomiasis is endemic in some countries of South-East Asia, and Latin America. It is due to the consumption of raw or insufficiently cooked meat or fish. Since the beginning of the eighties, there is an increasing number of cases of gnathostomiasis described in Western countries in travellers returning from endemic countries. IN THE SKIN OR THE VISCERA: Gnathostomiasis is a cause of cutaneous and/or visceral larva migrans syndrome. Some visceral involvement, more particularly neurological forms, may lead to significant morbidity and mortality. The diagnosis is occasionally confirmed by the identification of the Gnathostoma larva in the skin or viscera. Most often the diagnosis relies on epidemiological, clinical and biological (hypereosinophilia, positive serologic test) grounds. ALBENDAZOLE AND IVERMECTINE: The first line treatment is albendazole, 400 mg once or twice a day during 21 days. The efficacy of ivermectin needs to be assessed more precisely. Relapses may occur up to 24 months after apparent cure.

Animals↗
PubMed2004

Localized cutaneous leishmaniasis imported into Paris: a review of 39 cases.

BACKGROUND: Localized cutaneous leishmaniasis (LCL) is a common cause of dermatosis in travelers returning from the tropics. We describe the epidemiological, clinical, and biological aspects and therapeutic outcome of imported LCL. METHODS: A retrospective study of all cases of LCL observed from 1992 to 2000 in our tropical disease unit. Diagnosis was based on direct examination of skin smear and/or culture with identification of subsequent subspecies. RESULTS: Thirty-nine cases (25 males, 14 females; median age: 38 years) were included: 35 French travelers and four foreign immigrants; 15 cases were acquired in the Old World and 24 cases in the New World. The patients presented to our department with a median of 60 days after return. Thirteen patients had already consulted general practitioners, and the diagnosis was missed in five cases (38%). Five clusters were identified. The median number of skin lesions was two per patient. Diagnosis was established by direct microscopic examination in 36 cases (92%). Thirty-five patients were assessable for first-line treatment with antimonials (intramuscularly in 18, intralesionally in nine), intramuscular pentamidine isethionate or oral ketoconazole (four patients each). Twenty-five patients (71.4%) were cured. The remaining 10 patients were cured after one to three courses of other treatments. Overall adverse events occurred in 60% of the patients treated with antimonials and 37% of those treated with pentamidine. CONCLUSION: Imported LCL is still unrecognized by Western physicians. Clusters may be observed in groups of travelers. The therapeutic outcome is impaired by numerous but minor side-effects.

Adolescent↗
PubMed2004

Induction of the CD23/nitric oxide pathway in endothelial cells downregulates ICAM-1 expression and decreases cytoadherence of Plasmodium falciparum-infected erythrocytes.

Cytoadherence of parasitized red blood cells (PRBCs) to postcapillary venules and cytokine production are clearly involved in the pathogenesis of cerebral malaria. Nitric oxide and TNF-alpha have been proposed as major effector molecules both in protective and physiopathological processes during malaria infections. Nitric oxide production has been shown to be induced by engagement of CD23 antigen. This study aimed to investigate the potential role of the CD23/nitric oxide pathway in the control of the cytoadherence of PRBCs on human endothelial cells. We demonstrate that normal human lung endothelial cells (HLECs) are able to express the low affinity receptor for IgE (Fc in RII/CD23), following cell incubation with interleukin 4 or PRBCs. Ligation of the CD23 antigen by a specific anti-CD23 monoclonal antibody at the cell surface of HLECs was found to induce iNOS mRNA and protein expression, NO release and P. falciparum killing. In addition, the specific CD23-engagement on these cells also induced a significant decrease in ICAM-1 expression, an adhesion molecule implicated in PRBCs cytoadherence. These data not only described for the first time the expression of a CD23 antigen at the cell surface of endothelial cells but also suggest a possible new regulatory mechanisms via the CD23/NO pathway during malaria infection.

Animals↗
PubMed2003

Plasmodium falciparum--infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells.

During Plasmodium falciparum infection leading to cerebral malaria, cytokine production and cytoadherence of parasitized erythrocytes (PRBCs) to postcapillary venules are involved. We demonstrate that PRBC adhesion induces apoptosis in human endothelial cells (HLECs). PRBC adhesion modulated HLEC gene expression in tumor necrosis factor-alpha superfamily genes (Fas, Fas L, and DR-6) and apoptosis-related genes (Bad, Bax, caspase-3,SARP 2, DFF45/ICAD, IFN-gamma receptor 2, Bcl-w, Bik, and iNOS). Apoptosis was confirmed by (1) morphological modifications by electron microscopy, (2) annexin V binding, (3) DNA degradation, by measuring intracytoplasmic nucleosomes, and (4) caspase activity. The apoptotic stimulus was physical contact between HLECs and PRBCs and not parasite-secreted molecules. In addition, it was found that cytoplasmic (caspase 8) and mitochondrial (caspase 9) pathways were involved in this process. These data not only describe the direct apoptotic effect of PRBC adhesion on endothelial cells but also provide new useful tools that allow an evaluation of potential pharmaceuticals.

Animals↗
PubMed2003

The new drug combinations: their place in the treatment of uncomplicated Plasmodium falciparum malaria.

Malaria is a leading cause of morbidity and mortality in developing countries. Selection of mutant Plasmodium falciparum malaria strains under drug pressure has led to the development of drug resistance. There is a pressing need for effective, safe, practicable drug combinations that hve lower selection pressure. A review of the mein drug combinations, which are recently registered or are still under development, was undertaken, with special attention to the atovaquone-proguanil and artemether-lumefantrine combination.

Animals↗
PubMed2003

In vitro activities of 25 quinolones and fluoroquinolones against liver and blood stage Plasmodium spp.

The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii and P. falciparum were studied. All compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant P. falciparum grown in red blood cells. This inhibitory effect increased with prolonged incubation and according to the logarithm of the drug concentration. Grepafloxacin, trovafloxacin, and ciprofloxacin were the most effective drugs, with 50% inhibitory concentrations of <10 micro g/ml against both strains. Only grepafloxacin, piromidic acid, and trovafloxacin had an inhibitory effect against hepatic stages of P. falciparum and P. yoelii yoelii; this effect combined reductions of the numbers and the sizes of schizonts in treated cultures. Thus, quinolones have a potential for treatment or prevention of malaria through their unique antiparasitic effect against erythrocytic and hepatic stages of Plasmodium.

4-Quinolones↗
PubMed2002

[Ivermectin, a broad spectrum antiparasitic drug].

ACTIVITY: Ivermectine, derived from beta avermectines, monocyclic lactones produced by Streptomyces avermitilis, is a potent oral microfilaricide used by veterinaries since 1981. The anti-filarial activity is two-fold: both microfilaricide and embryotoxic in female adults; it has no activity on the latter. INDICATIONS: Ivermectine is the treatment of choice in onchocercosis, induced by the nematode Onchocerca volvulus, and was included in the onchocercosis control program (programme de contrôle de l'onchocercose (OCP) in 1987. Ivermectine has also demonstrated efficacy on other filaries (Wuchereria bancrofti, Loa loa), in intestinal nematodes (Ascaris lumbricoïdes, Strongyloides stercoralis) and in parasite nematodes in man (larva migrans ankylosis). ACCORDING TO THE RESULTS OF RECENT STUDIES: Its activity has been recently extended to ectoparasitosis: sarcoptes and pediculosis of the scalp.

Antiparasitic Agents↗
PubMed2002

Potential value of Plasmodium falciparum-associated antigen and antibody detection for screening of blood donors to prevent transfusion-transmitted malaria.

BACKGROUND: Malaria antibody detection is a valuable tool in the prevention of transfusion-transmitted malaria in countries with a high proportion of donors with travel exposure to malaria. The immunofluorescent antibody test (IFAT) is still the reference method, but it is not suitable for screening of blood donors. ELISA would be an interesting alternative to the IFAT, but it lacks sensitivity. STUDY DESIGN AND METHODS: To evaluate the potential value of a combined screening strategy based on malaria antigen and antibody detection, plasma samples from 203 patients infected with Plasmodium falciparum were tested with an ELISA for the detection of malaria antibodies (Malaria IgG CELISA, Cellabs) and a P. falciparum histidine-rich protein-2 kit (Malaria P.f., ICT Diagnostics) for the detection of malaria antigens. RESULTS: Among patients with positive IFAT results, CELISA had a sensitivity of 71 percent, whereas the combined screening tests (CELISA and Malaria P.f.) had a sensitivity of 88 percent (p < 0.001). Sequential samples from 50 patients were tested. The combined screening tests shortened the detection of seroconversion from 11.4 +/- 1.6 to 5.3 +/- 1.1 days (p < 0.001). CONCLUSION: Combined malaria antigen and antibody detection, with methods compatible with mass screening, may constitute an attractive alternative to the IFAT for blood donor screening.

Animals↗
PubMedDate not supplied

Illnesses in travelers returning from the tropics: a prospective study of 622 patients.

BACKGROUND: Although between 8 and 19% of travelers consult a doctor after returning from the tropics, the full spectrum of health complaints is unknown. METHODS: We analyzed the relative frequency of travel-associated health complaints in all travelers (immigrants returning from visiting their home countries, expatriates, business travelers, and tourists) consulting our department between November 2002 and May 2003. RESULTS: A total of 622 patients were studied (256 women, 366 men; median age 38 yr; 45.3% tourists, 33.8% immigrants, 14.1% expatriates, 6.7% business travelers). The median duration of travel was 36.9 days. The main destinations were Africa (57.6%) and Asia (26.4%). A total of 637 diseases were diagnosed, distributed as follows: skin diseases (23.4%), gastrointestinal infections (19.1%), respiratory tract infections (11.5%), malaria (8.8%), schistosomiasis (7.2%), viral hepatitis (4.1%), urinary tract infections (3.5%), sexually transmitted infections (3.5%), tuberculosis (2.7%), dengue fever (2.5%), and others (13.8%). Malaria and intestinal tract infections accounted for 21% and 23% of diagnoses in the 257 febrile travelers, respectively. Overall, 230 diagnoses (36.1%) corresponded to imported tropical diseases, the main imported diseases being malaria, schistosomiasis, amebiasis, gastrointestinal disorders caused by intestinal nematodes, and dengue fever. CONCLUSIONS: Tropical diseases are not the leading cause of consultation in travelers returning from the tropics. Immigrants are the travelers most at risk of common tropical diseases, with the noteworthy exceptions of dengue fever and invasive schistosomiasis.

Adolescent↗