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To improve the immunodiagnosis of human toxocaral disease, a sensitive and specific assay using the Western blotting procedure (WB) with excretory-secretory antigens from Toxocara canis larvae (TES) was developed and compared with the standard enzyme-linked immunosorbent assay method (TES-ELISA) using the same antigens. We tested groups of sera from laboratory animals or patients presenting with toxocariasis or other helminthic diseases and a group of sera from people dwelling in an area endemic for toxocariasis who exhibited hypereosinophilia. Statistically, the WB assay correlated well with TES-ELISA, but the former was more specific for banding patterns corresponding to low-molecular-weight fractions, thus avoiding problems of cross-reactivity with sera infected with other helminthic diseases.

Xavier Iriart, iriart.x@chu-toulouse.fr y Both authors contributed equally. 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 uniand multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprimsulfamethoxazole 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, gammaglobulin 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.

Toxocariasis is a helminth zoonosis caused by infection with the larvae of Toxocara spp. ascarid worms. Only two species, Toxocara canis and Toxocara cati, are recognised as causative agents of human disease. The best choice for serodiagnosis of the generalised forms of toxocariasis, visceral larva migrans (VLM) or covert toxocariasis, relies upon the initial use of TES-ELISA, after which any positive result should subsequently be tested by Western blotting (WB). Covert toxocariasis is mostly a benign infection, so a large majority of infected subjects are asymptomatic or have very few symptoms and therefore go undiagnosed. In this form, this helminthosis is often self-limiting, leaving residual specific antibodies. A positive serodiagnosis caused by residual antibodies that do not have any diagnostic significance can be associated with any infectious or non-infectious disease. If separated from the ongoing clinical and laboratory context, such a positive result has no diagnostic value and should be only taken into account after the possible etiologies of any observed syndromes have been ruled out. Unlike the methods used for the immunodiagnosis of bacterial, viral or protozoal (toxoplasmosis) infections, it is not possible with toxocariasis to assess the age of the presence of specific IgG using the levels of specific IgM because IgM antibodies can be found throughout the course of helminthiasis. The detection of other classes of immunoglobulins, namely IgE and IgA, the subclasses, namely IgG4 or circulating Ag was proven to be unable to discriminate between active and self-cured generalised toxocaral infections. Currently, the diagnosis of an active covert toxocariasis relies upon indirect arguments, e.g., the presence of otherwise unexplained symptoms along with blood eosinophilia and/or elevated levels of eosinophil cationic protein (ECP). This situation is far from ideal and more research should be carried out to solve this difficult problem.

Malaria is the third most significant cause of infectious disease in the world. The search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to classical drugs. Trioxaquines are synthetic hybrid molecules containing a trioxane motif (which is responsible for the antimalarial activity of artemisinin) linked to an aminoquinoline entity (which is responsible for the antiplasmodial properties of chloroquine). These trioxaquines are highly potent against young erythrocytic stages of Plasmodium falciparum and exhibit efficient activity in vitro against chloroquine-sensitive and -resistant strains of P. falciparum (50% inhibitory concentration, 4 to 32 nM) and are also active in vivo against P. vinckei petteri and P. yoelii nigeriensis in suppressive and curative murine tests. The trioxaquine DU1302 is one of these promising antimalarial agents. The present study confirms the absence of toxicity of this drug on cell lines and in a mice model. Moreover, DU1302 exhibits potent activity against gametocytes, the form transmitted by mosquitoes, as killing of the gametocytes is essential to limit the spread of malaria. The ease of chemical synthesis of this trioxaquine prototype should be considered an additional advantage and would make these drugs affordable without perturbations of the drug supply.

Trioxaquines are dual molecules that contain a trioxane motif linked to an aminoquinoline entity. Among the different compounds of this series, trioxaquine cis-15 (DU1302 c), prepared from alpha-terpinene, a cheap natural product, showed efficient antimalarial activity in vitro on both sensitive and resistant strains of Plasmodium falciparum (IC(50)=5-19 nM). A stereochemical description of this stable, nontoxic, and non-genotoxic antimalarial agent is detailed. Mice infected with P. vinckei were successfully treated with cis-15 in a four-day suppressive test. The doses required to decrease parasitemia by 50 % (ED(50)) were 5 and 18 mg kg(-1) d(-1) after intraperitoneal and oral administration, respectively. Parasitemia clearance was complete without recrudescence at an intraperitoneal dose of 20 mg kg(-1) d(-1).

Visceral larva migrans is apparently an endemic disease among adults in southwest France. Thirty-seven adults living in the Midi-Pyrenees region of France were confirmed as having visceral larva migrans based on an increased specific antibody titer to Toxocara canis as detected by enzyme-linked immunosorbent assay (ELISA) and by the Western blot method. The disease was characterized clinically by weakness, pruritus, rash, difficulty breathing, abdominal pain, and pathologically by allergic manifestations including eosinophilia and increased serum immunoglobulin (Ig) E levels. Conditional logistic regression analysis using a control group of 37 hospital patients with other conditions who were individually matched to patients with visceral larva migrans by age and sex revealed an increased risk for visceral larva migrans associated with hunting or living in a household with a hunter (odds ratio (OR) = 9.0, p = 0.02) and with living in a village of less than 500 persons (OR = 5.7, p = 0.04). Owning two or more dogs compared with owning one or no dogs increased the risk of visceral larva migrans for hunting or living in a household with a hunter (OR = 9.6 vs. OR = 4.5) and for persons living in nonhunting households (OR = 2.1 vs. OR = 1.0). These findings, however, could not be duplicated when 60 age- and sex-matched neighbors were used as a second control group.