Risk factors of Pneumocystis pneumonia in solid organ recipients in the era of the common use of posttransplantation prophylaxis.

Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni- and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim-sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma-globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

Simultaneous cutaneous infection due to Paecilomyces lilacinus and Alternaria in a heart transplant patient.

Paecilomyces lilacinus is an emerging pathogen in immunocompromised patients. We report here a case of cutaneous hyphomycosis in a 63-year-old heart transplant recipient caused by the simultaneous presence of 2 molds: Paecilomyces lilacinus and Alternaria alternata. The infection was successfully treated with local voriconazole followed by oral terbinafine.

In vitro anthelmintic activity of the essential oils of Zanthoxylum zanthoxyloides and Newbouldia laevis against Strongyloides ratti.

The need for new anthelmintic with no chemical residues is becoming urgent. In a program aiming at the evaluation of plant as sources of new active molecules, the anthelmintic activities of the essential oils (EOs) obtained from either Zanthoxylum zanthoxyloides seeds or Newbouldia laevis leaves were evaluated against Strongyloides ratti by analyzing the results of two in vitro bioassays. These two plants and their tested parts were retained after an ethnopharmacology survey that confirmed their use by small-scale farmers for treatment of small ruminants affected by digestive helminths. The plants were harvested in Benin, and their EO were obtained by hydrodistillation. The EO yield of extraction was 0.65% (w/w) of for Z. zanthoxyloides seeds and 0.05% (w/w) for N. laevis. The chemical compositions of the two EOs were analyzed by gas chromatography coupled with mass spectrometry. The major constituents of the EO from Z. zanthoxyloides consisted of the following compounds: γ-terpinene (18 %), undecane (15 %), valencene (8.3 %), decanal (8.3 %), and 3-carene (6.7 %). In contrast, the major constituents of the EO from N. laevis leaves consisted of the following compounds: ß-caryophyllene (36 %) and eugenol (5.8 %). An egg-hatching inhibition (EHI) assay was developed and a larval migration inhibition assay was used on S. ratti to examine the effects of the EOs and to evidence their inhibitory concentrations (IC(50) and IC(90)) values on this nematode. Furthermore, the toxicity of the two EOs on Vero cell line was evaluated. When tested on S. ratti egg hatching, the two EOs resulted in similar IC(50) values (19.5 and 18.2 µg/ml for Z. zanthoxyloides and N. laevis, respectively), which were about sevenfold higher than that of the control (thiabendazole, IC(50) = 2.5 µg/ml). Larval migration was inhibited at similar concentrations for: Z. zanthoxyloides (IC(50) = 46 µg/ml), N. laevis (IC(50) = 51 µg/ml), and the control [levamisole (IC(50) = 36 µg/ml)]. No cytotoxicity was found on Vero cells because both EOs had IC(50) values higher than 50 µg/ml. Therefore, we have concluded that the EOs from two plants, used in folk medicine, may contain compounds with anthelmintic activity and could be used as improved traditional medicines or, at least, as food additives in a combined treatment for the control of helminth infections.

How common is human toxocariasis? Towards standardizing our knowledge.

Our understanding of the global impact and cost of human toxocariasis is poor because there is insufficient clinical awareness and no clear repository for the efficacy of clinical, laboratory and treatment interventions. Uniform clinical and laboratory investigative approaches maximize disease diagnosis. International collaboration is required to develop web-based, professional educational support, surveillance questionnaires and standardized serodiagnostic criteria. Determining clinical benefits and treatment outcomes using less crossreactive antigens will enhance clinical and treatment interventions. Increased liaison will identify realistic occurrence and prevalence data and cost benefits of intervention. Web-based centres of excellence and repositories of current knowledge, which augment current veterinary and public health educational sites, should be supported. Expected outcomes should be capable of addressing the clinical and financial burdens of this treatable disease.

Diagnosis of congenital toxoplasmosis: prenatal and neonatal evaluation of methods used in Toulouse University Hospital and incidence of congenital toxoplasmosis.

The aim of this study was to determine the incidence of congenital toxoplasmosis (CT) and to assess the performances of prenatal and neonatal diagnoses. From 1994-2005, in Toulouse University Hospital, France, amniocentesis was performed on 352 pregnant women who were infected during pregnancy. All women were treated with spiramycin and pyrimethamine-sulfadoxine when prenatal diagnosis was positive. Among the 275 foetuses with follow-up, 66 (24%) were infected. The transmission rates of Toxoplasma gondii were 7%, 24% and 59% in the first, second and third trimesters, respectively. The sensitivity and specificity of PCR on amniotic fluid (AF) were 91% and 99.5%, respectively. One case was diagnosed by mouse inoculation with AF and six cases were diagnosed by neonatal or postnatal screening. The sensitivity and specificity of PCR on placentas were 52% and 99%, respectively. The sensitivity of tests for the detection of specific IgA and IgM in cord blood was 53% and 64%, respectively, and specificity values were 91% and 92%. In conclusion, PCR performed on AF had the highest levels of sensitivity and specificity for the diagnosis of CT. This permits an early diagnosis of most cases and should be recommended.

PCR-based methods to the diagnosis of imported malaria.

Rapid and precise diagnosis of malaria is needed to take care febrile patient returning from endemic areas. Since the first description of the diagnosis of Plasmodium infection by polymerase-chain-reaction (PCR), the role of this kind of molecular method in the laboratory diagnosis of imported malaria is still a topical question. PCR-based assays were found to be more sensitive and more specific than all conventional methods. The highest contribution of the molecular diagnosis is that a PCR negative result would ascertain the lack of any malaria infection, thus quickly orienting the investigations toward other aetiology. This technique should be now considered as the gold standard for the diagnosis of imported malaria.

[Urinary schistosomiasis and cancer]. / Schistosomose urogénitale et cancer.

The existence of a link between urinary schistosomiasis (US) and bladder carcinoma was first suspected by C. Goebel in 1905. In 1911, A.R Ferguson, who was a professor of Pathology and Microbiology at the Faculty of Medicine in Cairo, published a more detailed survey from 40 autopsies, and reported a likely association of bladder carcinoma with granulomas caused by US. Subsequently, published results from several studies reinforced Ferguson's hypothesis. Moreover, in most countries where US was endemic, association of high prevalence of bladder carcinoma with US had been pointed out. A further circumstantial evidence was a higher prevalence of bladder squamous cell carcinoma in areas endemic for SU, whereas urothelial carcinomas were more prevalent in areas which were free of SU. However, evidence of a positive correlation between SU and bladder carcinoma was delivered only many decades later, following the results from case-control studies which were adjusted on age, sex, type of dwelling and tobacco consumption. During SU, the mechanisms underlying the onset of bladder carcinoma are still poorly understood due to the lack of any convenient animal model. Classically, two processes are thought to be involved. Chronic inflammation inside bladder would be caused by granulomas centered by eggs, and would result in a neoplasmic evolution, after years. Moreover, alteration of the bladder dynamics would elicit urine stasis which in turn would cause repeated infection of bacterial or viral origin. Beside the high prevalence of squamous cell type, the natural history of bladder carcinomas caused by SU is similar to that of other malignant tumors of the bladder. Also the treatment and prognosis are identical. Albeit genital involvement is very frequent during SU, Schistosoma haematobium does not appear to be a cause of cancers of genital organs. Schistosoma mansoni and S. japonicum have been suspected to be associated with liver or colic carcinomas, but epidemiological studies have not yielded any firm evidence so far. The entire sequencing of S. haematobium genome, along with the recent availability of a more efficient mouse model, must provide a better understanding of the genesis of bladder carcinomas during SU. However, the key for a sharp decrease in both morbidity and mortality due to SU-linked carcinomas lies in a better control of haematobium schistosomiasis, such as observed in Egypt since 1970.

Prevalence of Plasmodium falciparum cytochrome b gene mutations in isolates imported from Africa, and implications for atovaquone resistance.

The atovaquone resistance of malaria parasites correlates with mutations in the cytochrome b gene. We sequenced the Plasmodium falciparum cytochrome b gene of 135 African isolates. Our data showed a high mutation rate (8.9%); however, the risk of emergence spreading of atovaquone-resistant P. falciparum strains could be limited.

Scedosporium apiospermum mycetoma with bone involvement successfully treated with voriconazole.

Treatment of Scedosporium apiospermum mycetoma usually requires limb amputation. A 49-year-old woman, from Ivory Coast, was diagnosed with Madura foot in 1995. She failed to respond to several treatments including itraconazole, fluconazole and co-trimoxazole, and refused limb amputation. In December 2002 she was admitted to hospital in France with a painful, swollen right leg and foot. She had no fever and C-reactive protein was 120 mg/l. Magnetic resonance imaging (MRI) confirmed the destruction of tarsus bones with a tibia extension. Voriconazole (400 mg/day) treatment was initiated in March 2003; a significant clinical improvement was observed within 4 months as confirmed by C-reactive protein (16 mg/l) and MRI. Voriconazole was maintained for 18 months with good tolerance. Cholestasis appeared after the first month and remained stable. In October 2004 voriconazole was discontinued due to side effects on the liver (alanine aminotransferase 17 times the normal level); MRI showed impressive regression of bone lesions. As of July 2005, the patient remains clinically well. Voriconazole appears to be a promising drug for the treatment of S. apiospermum mycetomas.

[Treatment of cosmopolitan parasitic diseases]. / Traitement des parasitoses cosmopolites.

Cosmopolitan parasitic diseases are often unrecognized and misdiagnosed. Treatment can be difficult due mainly to a lack of the therapeutic drugs. The purpose of this review is to update knowledge about the therapy of anisakiasis, cystic echinococcosis, fascioliasis, giardiasis, pinworm/tapeworm infections, strongyloidiasis, and toxoeariasis.

[Parasitic dead-end: update]. / Impasses parasitaires: quoi de neuf?

Parasitic dead-ends occur when a parasite is unable to establish a permanent interaction in an unnatural host. Although the likelihood of successful reproduction by the pathogenic agent is nul, parasitic dead-end heralds capture of new parasites and therefore expansion of the host range. Angiostrongyliasis due to A. cantonensis or A. costaricensis, anisakiasis, Ancylostoma caninum infection, gnathostomiasis and sparganosis are undoubtedly emerging zoonoses of particular medical interest. Prevention of these diseases relies on abstinence from eating raw meat from invertebrates or cold-blooded (poikilotherm) vertebrates (e.g. used in exotic dishes). These guidelines must be included in recommendations to travelers.

Ex vivo and in vitro impairment of CD36 expression and tumor necrosis factor-alpha production in human monocytes in response to Plasmodium falciparum-parasitized erythrocytes.

Severe malaria is associated with the failure of host defenses to control parasite replication, with the excessive secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), and with the sequestration of parasitized erythrocytes (PEs) in the microcirculation of vital organs. The scavenger receptor CD36, known as a major sequestration receptor, has also been identified as an important factor in mediating nonopsonic phagocytosis of PEs by monocytes and macrophages. The specific consequence of this phagocytosis is a decrease in parasite-induced TNF-alpha secretion. We evaluated the variations in CD36 level and in lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes from Plasmodium falciparum-infected patients and in vitro in the presence of PEs. Both the monocytes from infected patients and from in vitro culture showed a decrease of CD36 expression and a reduced production of TNF-alpha induced by LPS. Using incubation assays with no contact between monocytes and PEs, or in the presence of a soluble supernatant obtained from the incubation of monocytes and PEs, this study shows that decreased CD36 expression was posttranscriptional and not directly related to PEs phagocytosis. In addition, these culture models suggest that the reduced capacity of TNF-alpha production occurred in 2 phases. The early phase (24 hr) appeared to be CD36 dependent and the second phase (48 hr) was due to a soluble factor produced by PEs. These observations suggest that the control of the TNF-alpha production in malaria by monocytes was not entirely dependent on the phagocytosis of PEs by CD36 and that soluble factors produced by PEs could play a role in this process.

Contribution of PCR-based methods to diagnosis and management of imported malaria.

Since the first description, in 1990, of the diagnosis of Plasmodium falciparum infection by polymerase-chain-reaction (PCR), the role of this kind of molecular method in laboratory diagnosis of imported malaria is still a topical question. Various molecular assays have been used, the first of which was hybridization using labeled probes in 1984. When compared to thick blood smear, this test displayed a sensitivity ranging from 65% to 81% and specificity was close to 100%. The next technical improvement was the introduction of the so-called polymerase chain reaction (PCR), the principle of which was described in 1985. In 1993, a PCR-based assay detecting all four Plasmodium species was published, followed by different variants of this method. By the turn of the century, novel real-time PCR slashed workaround time, which dropped from 2 1/2 hours to less than 1 hour. Moreover, automatic reading with no human action on PCR products reduced the risks of contamination. The first application of real-time PCR to the diagnosis of malaria was published in 2001. PCR-based assays were found to be more sensitive than all conventional methods. Variations in sensitivity were probably due to different medical practices as well as to the proportion of various types of subjects (travelers under chemoprophylaxis, immigrants from malaria-endemic areas) in the population undergoing malaria diagnosis. The target of the primers was also of crucial importance: for the detection of P. falciparum, the most efficient assays amplified either the gene SSUrRNA, or Pf155/RESA, or Cox 1. Specificity of PCR results is guaranteed by the nature of the target for primers or probes, as determined by the studies of the Plasmodium genome whose results are available in GenBank. PCR use often corrected the results of Plasmodium species identification by microscopy and PCR-based methods were found to be the most efficient for the detection of mixed infections. Concerning the diagnosis of imported malaria, it appears clearly that PCR should be considered as second-line method which can be especially interesting, as a negative result rules out malaria in febrile patients. However, the use of PCR assays appears to be restricted to health centers, such as University Hospitals, for whom malaria identification is an important and routine problem. In the future, the detection of mutations related to drug resistance could be used to orient anti-malarial therapy.

Zoonotic roundworm infections.

The larval stage of several animal parasites can infect humans and produce severe disease. Visceral and ocular larval migrans caused by the common dog roundworm, Toxocara canis, are two well-recognized clinical syndromes. With the wider availability of serodiagnostic tests for toxocaral infection, other syndromes characterized by neuropsychologic deficits, epilepsy, asthma, abdominal distress, and chronic allergy have been described. Treatment with corticosteroids in conjunction with anthelminthic drugs may be life- or sight-saving. Recognition of the risk factors for infection is key to prevention, reinfection, and more serious illness.

One year's experience with the polymerase chain reaction as a routine method for the diagnosis of imported malaria.

Given the problems encountered in westernized countries with the laboratory diagnosis of malaria, namely sensitivity of the conventional methods and detection of mixed infections, a polymerase chain reaction (PCR)-based diagnosis has been developed and routinely used. The PCR used two sets of primers to simultaneously detect any infection due to the genus Plasmodium, or to the species P. falciparum. The PCR results were available within six hours. Five hundred twenty-nine patients were tested, of whom 136 were found positive by the PCR, and only 104 by the quantitative buffy coat (QBC) method. The 32 discrepancies were analyzed on the basis of the clinical data, and technical, molecular, and sequencing findings to ascertain the presence of Plasmodium DNA. The PCR-based diagnosis of malaria appeared to be a useful tool that was suitable as a second-line method when the results of conventional techniques were negative in patients presenting a syndromeconsistent with malaria, as well as yielding an accurate species identification.

Seroprevalence of retroviral infections among pregnant women in Martinique (French West Indies).

A seroepidemiologic study of human T cell lymphotrophic virus type-1 (HTLV-1) and human immunodeficiency virus (HIV) infections was carried out in Martinique among 467 pregnant women receiving prenatal care at the Martinique Department for the Protection of Motherhood and Childhood. A seroprevalence rate of 1.93% was found for HTLV-1 infection. No HIV serum marker was observed. Given the epidemiology of these viral diseases, it is suggested that serologic status should be determined for all pregnant women on this island. A further, large-scale, prospective survey of HIV seroprevalence in Martinique should be performed to confirm the results of the present study.

Epidemiology of human toxocariasis in La Réunion.

In La Réunion island (Indian Ocean) a seroepidemiological survey for toxocariasis was carried out among 387 subjects over 15 years old by Western blotting using Toxocara canis excretory-secretory larval antigens; 92.8% of the sera were positive. Statistical study, including logistic regression analysis, showed a significant correlation of Western blot results with sex, age, and absence of water supply. The final logistic model demonstrated that only the last 2 factors were significant multiplicative risk factors for toxocariasis. Sex was an independent risk factor. With this level of infection, we suggest that further surveys of ocular toxocariasis in children and teenagers of La Réunion would be advisable.

Outbreak of trichinellosis in the Midi-Pyrénées region of France January - March 1998.

Two outbreaks of trichinellosis in the Tarn et Garonne, département, France were reported by the departmental health autorities on 2 March 1998, to the Réseau National de Santé Publique (RNSP). An epidemiological investigation began on 3 March in order to.

Outbreak of trichinellosis in the Midi-Pyrenees region of France January - March 1998.

Two outbreaks of trichinellosis in the Tarn et Garonne, departement, France were reported by the departmental health autorities on 2 March 1998, to the Reseau National de Sante Publique (RNSP). An epidemiological investigation began on 3 March in order to

[Toxocara canis meningoradiculitis]. / Méningo-radiculite à toxocara canis.

Various neurological pictures attributed to human toxocariasis are sparsely reported in the literature. A case of toxocaral infection presenting as meningoradiculitis is described herewith. Etiological diagnosis was oriented by the finding of an eosinophilia in the spinal fluid, then confirmed by the result of the immunodiagnosis of toxocariasis from both serum and spinal fluid.