Evidence that prevention, diagnosis and treatment of toxoplasmosis is beneficial developed as follows: antiparasitic agents abrogate Toxoplasma gondii tachyzoite growth, preventing destruction of infected, cultured, mammalian cells and cure active infections in experimental animals, including primates. They treat active infections in persons who are immune-compromised, limit destruction of retina by replicating parasites and thereby treat ocular toxoplasmosis and treat active infection in the fetus and infant. Outcomes of untreated congenital toxoplasmosis include adverse ocular and neurologic sequelae described in different countries and decades. Better outcomes are associated with treatment of infected infants throughout their first year of life. Shorter intervals between diagnosis and treatment in utero improve outcomes. A French approach for diagnosis and treatment of congenital toxoplasmosis in the fetus and infant can prevent toxoplasmosis and limit adverse sequelae. In addition, new data demonstrate that this French approach results in favorable outcomes with some early gestation infections. A standardized approach to diagnosis and treatment during gestation has not yet been applied generally in the USA. Nonetheless, a small, similar experience confirms that this French approach is feasible, safe, and results in favorable outcomes in the National Collaborative Chicago-based Congenital Toxoplasmosis Study cohort. Prompt diagnosis, prevention and treatment reduce adverse sequelae of congenital toxoplasmosis.Key words: congenital toxoplasmosis -prevention -treatment antimicrobial treatment of T. gondii in tissue culture and animal models eliminates actively replicating parasites and leads to prevention or resolution of signs of disease in these models (Eyles & Coleman 1953a, b, 1955a, b, Frenkel & Hitchings 1957, Garin et al. 1968, Brus et al. 1971, Beverley et al. 1973, Feldman 1973, Sheffield & Melton 1975, Grossman & Remington 1979, Garin & Paillard 1984, Mack & McLeod 1984, Picketty et al. 1990, Hohlfels et al. 1994, Schoondermarkvan de Ven et al. 1995, Derouin 2001, Meneceur et al. 2008; treatment of ocular toxoplasmosis, toxoplasmosis in immune-compromised persons and of congenital toxoplasmosis in humans abrogates symptoms and signs of active infection and improves outcomes (Perkins et al. 1956, Kräubig 1963, Thalhammer 1969, Couvreur et al. 1984a, 1993, Desmonts & Couvreur 1984, Daffos et al. 1988, Hohlfeld et al. 1989, 1994a, b, Dannemann et al. 1992, 2006a, Torre et al. 1998, Boyer et al. 2000, Thulliez 2001, Brézin et al. 2003, Kim 2006, Berrebi et al. 2007, Petrof & McLeod 2002, SY-ROCOT et al. 2007, the more rapidly human congenital toxoplasmosis is diagnosed and treated, the shorter the time available for tissue destruction by the parasite and thus the better the outcomes , SYROCOT et al. 2007; and detection of the infection acquired during the gestation of the fetus and rapid initiation of treatment, is often associated with favorable outcomes (Daffos et al. 1988, Hohlfeld et al. 1989, Fo...
Lung infections play a critical role in cystic fibrosis (CF) pathogenesis. CF respiratory tract is now considered to be a polymicrobial niche and advances in high-throughput sequencing allowed to analyze its microbiota and mycobiota. However, no NGS studies until now have characterized both communities during CF pulmonary exacerbation (CFPE). Thirty-three sputa isolated from patients with and without CFPE were used for metagenomic high-throughput sequencing targeting 16S and ITS2 regions of bacterial and fungal rRNA. We built inter-kingdom network and adapted Phy-Lasso method to highlight correlations in compositional data. The decline in respiratory function was associated with a decrease in bacterial diversity. The inter-kingdom network revealed three main clusters organized around Aspergillus, Candida, and Scedosporium genera. Using Phy-Lasso method, we identified Aspergillus and Malassezia as relevantly associated with CFPE, and Scedosporium plus Pseudomonas with a decline in lung function. We corroborated in vitro the cross-domain interactions between Aspergillus and Streptococcus predicted by the correlation network. For the first time, we included documented mycobiome data into a version of the ecological Climax/Attack model that opens new lines of thoughts about the physiopathology of CF lung disease and future perspectives to improve its therapeutic management. Lung infections play a critical role in cystic fibrosis (CF) pathogenesis where they can lead to significant acute decrease of lung function, known as CF pulmonary exacerbation (CFPE). Developments of next-generation sequencing (NGS) approaches allowed us to understand microbiome composition that can contribute to lung physiopathology in both healthy individuals and patients with lung disease. More recently, NGS together with advances into statistical network inference tools allowed to analyze the microbial airway communities, appreciate the inter-kingdom equilibrium of respiratory floras, and therefore develop understanding of microbial communities as a whole 1-7. Acute CFPEs represent major clinical events that significantly decline the lung function, contribute to disease progression and require adapted, prompt anti-infectious treatment 8-11. Omics approaches confirmed associations between bacterial community and exacerbation 12-20. Apart from bacteria that are well known agents causing dramatic recurrent CFPEs, respiratory viruses have been recently found to be associated with CFPE, independently
Primary maternal infection with toxoplasmosis during pregnancy is frequently associated with transplacental transmission to the fetus. This study was conducted to test the utility of a polymerase chain reaction (PCR) assay to detect recent infections with Toxoplasma in pregnant women. One hundred forty-eight women with high-risk pregnancies who had abnormal pregnancy outcomes (cases) and 100 with normal pregnancies (controls) were tested for the presence of Toxoplasma DNA in their blood by a nested PCR and specific antibodies to Toxoplasma by an enzyme-linked immunosorbent assay. The IgG results of the cases differed significantly from those of the controls (54% and 12%, respectively; P < 0.02). Four (2.7%) of the cases were IgM positive, but none of the controls were positive. Detection of Toxoplasma DNA in 20 (8.1%) of the IgG-positive cases suggests a recent infection. The risk factors associated with the infection were eating raw meat and contact with soil. The diagnostic serology of recent infection in early pregnancy could be confirmed by a positive Toxoplasma-specific PCR result in blood samples collected in the first half of pregnancy, even in the presence of serologic results difficult to interpret due to the lack of sequential follow-up during pregnancy.
A new PCR system including a pair of primers, a probe and an internal control were designed from the B1 gene of Toxoplasma gondii. The system described allowed the detection of less than 10 tachyzoites of the RH strain of T. gondii. Among 21 amniotic fluid samples, this system diagnosed the cases of congenital toxoplasmosis which were simultaneously diagnosed using mice inoculation, in vitro culture, and serology from both amniotic fluid and fetal blood. These results show that these new primers allow for a highly sensitive detection of T. gondii DNA.
Itraconazole, a new triazole antifungal agent, has marked in vitro activity against filamentous fungi, particularly Aspergillus. We studied three groups of patients suffering from aspergillosis (16 cases): six affected with aspergilloma, three with allergic bronchopulmonary aspergillosis and seven with invasive aspergillosis. The survey consisted in clinical, radiological, mycological and serological evaluations with respect to drug plasma levels. Itraconazole was given at a dosage of 200-400 mg day-1 for periods ranging from 14 to 488 days. Out of the 16 patients, nine responded to therapy (recovery or improvement) and one failed to respond. Three patients improved but experienced relapses and three others could not be evaluated because of liver function disorders, so that treatment had to be stopped prematurely.
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