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Biomedical subjects

D Camus

Publications and source records attributed to D Camus.

At least 19 recordsLinked to original sources
PubMed2004

Immunocompetent hosts as a reservoir of pneumocystis organisms: histological and rt-PCR data demonstrate active replication.

The present study was conducted to further examine recent data suggesting that pneumocystosis could be transmitted between patients and healthcare workers in the hospital environment, as has been proven with Pneumocystis-infected SCID mice and immunocompetent Balb/c mice. Using an experimental design (i.e., SCID-Balb/c mouse airborne transmission system), the present work found that healthy host-to-healthy host transmission of Pneumocystis organisms can occur, and that 'second' healthy contacts are able to transmit the infectious organisms to immunocompromised hosts. Further tests designed to explore the behavior of Pneumocystis organisms in the lungs of immunocompetent hosts were performed using histological and molecular approaches (e.g. testing the expression of both cyclin-dependent serine-threonine kinase and heat-shock 70 protein in Pneumocystis). The results showed Pneumocystis organisms were able to replicate in the lungs of immunocompetent hosts, which indicates these hosts are a reservoir for Pneumocystis spp.

Animals↗
PubMed2004

Molecular typing of Pneumocystis jirovecii found in formalin-fixed paraffin-embedded lung tissue sections from sudden infant death victims.

Previous studies have provided histological evidence of an association between primary Pneumocystis infection and sudden infant death syndrome (SIDS). The aim of this work was to determine the species of clustered Pneumocystis organisms found in formalin-fixed paraffin-embedded (FFPE) lung tissue sections from Chilean sudden infant death (SID) victims. This approach needed first to optimize a DNA extraction method from such histological sections. For that purpose, the QIAamp DNA Isolation from Paraffin-Embedded Tissue method (Qiagen) was first tested on FFPE lung tissue sections of immunosuppressed Wistar rats inoculated with rat-derived PNEUMOCYSTIS: Successful DNA extraction was assessed by the amplification of a 346 bp fragment of the mitochondrial large subunit rRNA gene of the Pneumocystis species using a previously described PCR assay. PCR products were analysed by direct sequencing and sequences corresponding to Pneumocystis carinii were found in all the samples. This method was then applied to FFPE lung tissue sections from Chilean SID victims. Pneumocystis jirovecii was successfully identified in the three tested samples. In conclusion, an efficient protocol for isolating PCR-ready DNA from FFPE lung tissue sections was developed. It established that the Pneumocystis species found in the lungs of Chilean SID victims was P. jirovecii.

Animals↗
PubMed2004

Polymicrobial candidaemia revealed by peripheral blood smear and chromogenic medium.

Candida spp are the fourth most common group of nosocomial pathogens isolated from patients on medical, surgical, and intensive care wards. Polymicrobial candidaemia has rarely been described. The diagnosis of candidaemia from peripheral blood smears has not been widely reported. This report describes the case of a young woman suffering from Ewing's sarcoma who developed a syndrome of septic shock. Deep fungal infection was diagnosed from a systematic peripheral blood smear and yeasts were isolated within 24 hours. A subculture on CHROMagar Candida allowed the differentiation and presumptive identification of Candida tropicalis and Candida krusei. Species identification was confirmed by the ID 32C system. This report underlines the usefulness of peripheral blood smears in the diagnosis of fulminant deep fungal infections, and of a differential isolation medium in the rapid presumptive identification of clinically important yeast species from clinical samples. This medium is particularly useful for the detection of mixed fungal infections, allowing early and better adapted antifungal treatment.

Adolescent↗
PubMed2002

[Life-threatening Plasmodium falciparum parasitemia, in an infant returning from the tropics].

INTRODUCTION: Severe falciparum malaria is a polymorphous life-threatening disease. Hyperparasitemia is rare among non-immune children returning from tropical areas. CARE REPORT: We report a case of an infant returning from Ivory Coast who presented with fever, prostration and marked thrombocytopenia (22,000 platelets/mm(3)). Blood slide showed Plasmodium falciparum ring forms. Parasite density dramatically increased from 1.7% to 45%, and the child developed several features of severe malaria, according to WHO definition. CONCLUSION: In this non-immune infant, prostration and thrombopocytopenia seemed to be earlier predictors of severity than hyperparasitemia and other WHO criteria, which have not been yet validated in travelling children.

Animals↗
PubMed2002

[Clinical studies using the combination atovaquone-proguanil as malaria prophylaxis in non-immune adult and child travelers].

Prophylaxis for short-term travel in malaria-endemic areas can be difficult for two reasons. The first is that currently available antimalarial drugs are becoming less effective because of the ability of the parasite to adapt to drug pressure. The second involves poor compliance with chemoprophylactic regimens due to the highly restrictive conditions of administration and adverse drug side-effects, especially in "healthy" subjects. The combination of atovaquone/proguanil (Malarone) could provide an answer to both these problems since it is not only effective on multiresistant strains of Plasmodium falciparum but also simplifies the conditions of administration and shows good tolerance in adults and children.

Adolescent↗
PubMed2001

In vitro and in vivo antimalarial activity of ferrochloroquine, a ferrocenyl analogue of chloroquine against chloroquine-resistant malaria parasites.

Previous studies have shown that ferrochloroquine (FQ) exhibited an antimalarial activity against Plasmodium spp. The present work confirmed this activity, described the curative effect on P. vinckei and investigated the FQ toxicity in vitro and in vivo. The in vitro and in vivo growth inhibition of P. falciparum and P. berghei N, respectively, showed that FQ antimalarial activity was 1.5-10 times more potent than chloroquine. FQ completely inhibited the in vivo development of both chloroquine-susceptible and resistant P. vinckei strains and protected mice from lethal infection at a dose of 8.4 mg kg(-1) day(-1) given for 4 days subcutaneously or orally. This curative effect was 5-20 times more potent than chloroquine, according to the strains' resistance to chloroquine. At this curative dose, no clinical changes were observed in mice up to 14 days after the last administration. Nevertheless, the acute toxicity and lethality of ferrochloroquine seemed to be dependent on gastric surfeit. The FQ security index determined in vitro confirmed that it might be a promising compound.

Administration, Oral↗
PubMed2001

Contribution of serological tests and blood culture to the early diagnosis of systemic candidiasis.

The isolation of Candida species from a single blood culture is considered sufficient evidence for the initiation of systemic antifungal therapy. However, blood cultures still lack sensitivity. Previous reports have suggested that the combined serological detection of mannanemia and anti-mannan antibodies may be useful for the diagnosis of systemic candidiasis caused by Candida albicans (specificity and sensitivity 93% and 80%, respectively). In this study, serological tests to detect Candida albicans mannan and Candida albicans antibodies (Platelia Candida Antigen and Antibody tests; Bio-Rad, France) were applied retrospectively to a series of patients with at least one Candida-positive blood culture and from whom at least one serum sample, taken before or on the day of blood culture, was available. Forty-five patients were selected, including 23 infected by Candida albicans, 4 by Candida glabrata, 9 by Candida tropicalis, 5 by Candida parapsilosis, and 4 by Candida krusei. Serological tests were positive in 73% of patients at least 2 days, and in some patients, up to 15 days before blood cultures became positive. These data suggest that serological surveillance of at-risk patients using the Platelia Candida tests could result in earlier initiation of antifungal therapy, especially when used in conjunction with blood cultures. In this way, more efficient management of nosocomial infections caused by Candida species can be achieved.

Candidiasis↗
PubMed2001

[Human nasal myiasis due to Oestrus ovis].

One case of human nasal myiasis caused by second and third instar larvae of Oestrus ovis was observed in Lille (North France). Oestrosis is a common myiasis of sheep and goats in Mediterranean and Tropical countries. The authors examine the oestrosis pathogenesis in the usual host (sheep) or in humans, and analyse the epidemiology, the symptomatology and the treatment of human oestrosis.

Aged↗
PubMed2001

Molecular characterization of Cryptosporidium isolates obtained from humans in France.

Cryptosporidium parvum is usually considered the agent of human cryptosporidiosis. However, only in the last few years, molecular biology-based methods have allowed the identification of Cryptosporidium species and genotypes, and only a few data are available from France. In the present work, we collected samples of whole feces from 57 patients from France (11 immunocompetent patients, 35 human immunodeficiency virus [HIV]-infected patients, 11 immunocompromised but non-HIV-infected patients) in whom Cryptosporidium oocysts were recognized by clinical laboratories. A fragment of the Cryptosporidium 18S rRNA gene encompassing the hypervariable region was amplified by PCR and sequenced. The results revealed that the majority of the patients were infected with cattle (29 of 57) or human (18 of 57) genotypes of Cryptosporidium parvum. However, a number of immunocompromised patients were infected with C. meleagridis (3 of 57), C. felis (6 of 57), or a new genotype of C. muris (1 of 57). This is the first report of the last three species of Cryptosporidium in humans in France. These results indicate that immunocompromised individuals are susceptible to a wide range of Cryptosporidium species and genotypes.

AIDS-Related Opportunistic Infections↗
PubMed2000

Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team.

BACKGROUND: Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers. METHODS: In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory. FINDINGS: 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015). INTERPRETATION: Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.

Adolescent↗
PubMed2000

Molecular cloning, expression analysis and iron metal cofactor characterisation of a superoxide dismutase from Toxoplasma gondii.

A genomic region of 12 kb encompassing the gene encoding the superoxide dismutase (SOD) of Toxoplasma gondii has been cloned. The gene contains four exons of 121, 42, 381 and 59 bp which are separated by three introns of 321, 202, and 577 bp, respectively. The open reading frame can be translated into a protein of 201 amino acids with a molecular mass of 22.6 kDa. Alignment indicated that it is a FeSOD, a type only found in bacteria, protozoa and chloroplast of higher plants. Recombinant SOD was expressed in a Escherichia coli double mutant lacking both MnFeSOD and FeSODs. The presence of iron as metal cofactor was confirmed by measurements of iron by absorption mass spectrometry and electron paramagnetic resonance studies. Semi-quantitative reverse transcribed polymerase chain reaction experiments showed a similar amount of SOD transcripts in two developmental stages of T. gondii. Antibodies raised against the purified recombinant protein detected SOD protein in both bradyzoite and tachyzoite forms suggesting this SOD might be essential for the intracellular growth of both developmental stages. Southern blot analysis indicated that SOD occured as a single copy gene in T. gondii genome.

Amino Acid Sequence↗
PubMed2000

Novel ferrocenic artemisinin derivatives: synthesis, in vitro antimalarial activity and affinity of binding with ferroprotoporphyrin IX.

Following our search for novel compounds with high antimalarial activity, a series of artemisinin (QHS) derivatives containing a ferrocenic nucleus was prepared and tested in vitro against Plasmodium falciparum strains. Two new metallocenic derivatives (1 and 3) were found as potent as QHS. All compounds showed a capacity to bind with ferroprotoporphyrin IX. A decrease in the Soret band absorbance of ferroprotoporphyrin IX, resulting from the addition of different drugs concentrations, was shown. The association stoichiometry of compounds to ferroprotoporphyrin IX appears to be 1:2 at equilibrium, with an intermediate 1:1 complexation. These results appear to strengthen the role of adducts between artemisinin derivatives and heme in generation of artemisinin radicals. Such interaction of artemisinin ferrocenyl derivatives with ferroprotoporphyrin IX and its biological significance could form a basis in future drug development.

Animals↗
PubMed1999

Analysis of genetic diversity at the iron-containing superoxide dismutase locus in Plasmodium falciparum wild isolates.

In order to investigate the genetic diversity of iron-containing superoxide dismutase (FeSOD) from Plasmodium falciparum, a potential anti-malarial therapeutic target, we cloned and sequenced Plasmodium FeSOD from 26 blood samples from non-infected patients. Fifteen clones had the same nucleotide sequence as that of the FeSOD gene of the P. falciparum strain HB3 cultivated in vitro. The other 11 clones presented mutations responsible for punctual amino acid changes which did not modify key residues for the function or the structure of the enzyme. The high sequence conservation between FeSOD from the isolates confirms that this enzyme could represent a therapeutic target.

Amino Acid Sequence↗
PubMed1999

Isolation and characterization of a subtractive library enriched for developmentally regulated transcripts expressed during encystation of Toxoplasma gondii.

To survive within infected hosts, Toxoplasma gondii undergoes profound metabolic and morphological changes by differentiating into a cyst characterized by its resistance to the immune system and chemotherapy. The stimulus that triggers Toxoplasma encystation and the molecular mechanisms regulating the bradyzoite phenotype are still unknown. Here, we developed a differentiation method in conjunction with a selective and subtracted cDNA strategy devised to identify developmentally regulated transcripts. We isolated and analyzed 65 cDNA clones. In addition to bradyzoite specific cDNAs previously reported, we demonstrate that twelve genes are exclusively or preferentially transcribed in the encysted bradyzoite forms of T. gondii using semi-quantitative RT-PCR. Among cDNAs identified, are those encoding predicted homologues of chaperones (mitochondrial heat shock protein 60, T-complex protein 1), DNA-damage repair protein, phosphatidylinositol synthase, glucose-6-phosphate isomerase and enolase. The identification of these genes opens the way for further study of molecular mechanisms controlling gene expression during T. gondii encystation.

Animals↗
PubMed1999

Cloning and characterization of iron-containing superoxide dismutase from the human malaria species Plasmodium ovale, P. malariae and P. vivax.

The iron-containing superoxide dismutase (FeSOD) gene from three human malaria species, namely Plasmodium ovale, P. malariae and P. vivax, was amplified by polymerase chain reaction, cloned and then sequenced. Comparisons of their deduced amino acid sequences with that of the FeSOD from P. falciparum revealed a very low polymorphism at the FeSOD locus in human malaria species. One P. ovale and the P. vivax FeSOD genes presented the same nucleotide sequence as that of the P. falciparum strain HB3 whereas the second P. ovale and the P. malariae genes exhibited two punctual mutations. These mutations did not affect the function and structure of the enzyme. The FeSOD polymorphism was so low that no phylogenetic relationship among human malaria species could be proposed, but this conservative structure strengthened the potentiality of this enzyme as a possible target for antimalarial drugs.

Amino Acid Sequence↗
PubMed1999

Synthesis and antimalarial activity in vitro of potential metabolites of ferrochloroquine and related compounds.

In man, the two major metabolites of the antimalarial drug chloroquine (CQ) are monodesethylchloroquine (DECQ) and didesethylchloroquine (di-DECQ). By analogy with CQ, the synthesis and the in vitro tests of some amino derivatives of ferrochloroquine (FQ), a ferrocenic analogue of CQ which are presumed to be the oxidative metabolites of FQ, are reported. Desmethylferrochloroquine 1a and didesmethylferrochloroquine 2 would be more potent against schizontocides than CQ in vitro against two strains (HB3 and Dd2) of Plasmodium falciparum. Other secondary amino derivatives have been prepared and proved to be active as antimalarial agents in vitro, too.

Animals↗