J Aubertin

Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients

Objective: To study the predictive value of anti‐Toxoplasma gondii antibody titres for the occurrence of toxoplasmic encephalitis (TE) in HIV‐infected patients. Methods: Data from the placebo arm of a trial of primary prophylaxis for TE (ANRS 005/ACTG 154) were analysed. Patients included had CD4+ cell counts < 200 × 106/l and a positive Toxoplasma serology. Immunoglobulin (Ig) G and IgM Toxoplasma antibody titres at entry were retrospectively determined by enzyme‐linked immunosorbent assay and agglutination on serum samples in a single laboratory. Incidence of TE was estimated by Kaplan‐Meier method and a Cox model was used to study the predictive value of antibody titres, adjusted for other covariates. Results: All 164 patients studied were positive for IgG antibodies and one had IgM antibodies. After a mean follow‐up of 16 months, 31 cases of TE were documented. One‐year incidence of TE was significantly higher in patients with IgG titres ≥ 150 IU/ ml (23.7%) than in patients with titres < 150 IU/ml (7.7%; relative risk, 3.1; P < 0.003). IgG titres remained significantly associated with the occurrence of TE (relative risk, 3.3; P < 0.005) in the Cox model. Predictive value of IgG titres did not differ according to baseline CD4+ cell counts. Conclusion: In patients with CD4+ cell counts < 200×106/l, IgG anti‐Toxoplasma antibody titre is a prognostic factor of occurrence of TE, with a higher risk for titres ≥ 150 IU/ml. This finding should reinforce the recommendation of specific prophylaxis in these patients.

Effects of red wine, tannic acid, or ethanol on glucose tolerance in non-insulin-dependent diabetic patients and on starch digestibility in vitro.

This study examines the effect of moderate intake of red wine, tannic acid, or ethanol during a meal in type 2 diabetic patients and the influence of tannic acid on the digestibility of starch by alpha-amylase. Thirty non-insulin-dependent diabetes mellitus (NIDDM) patients aged 53 +/- 6 years were studied (in vivo study) 10 of whom received red wine (200 mL), 10 tannic acid (150 mg), and 10 ethanol (16 g) with their midday meal (600 calories, 65 g carbohydrate, 20 g lipid, and 34 g protein). All patients were tested on two occasions (water or placebo v wine, alcohol, or tannic acid). The influence of tannic acid (0.25, 0.5, and 1 mg) on the digestibility of starch (100 mg) by alpha-amylase (100 U) was tested in vitro by sequential incubation at 37 degrees C (in vitro study). The maximum glucose excursion after lunch was 2.6 +/- 0.8 mmol/L at 90 minutes (T90) for water and 1.8 +/- 0.9 mmol/L at T90 for red wine taken with the meal. The values at T60 and T90 were significant (P < .01). Comparable results were obtained with tannic acid alone (nonalcoholic component of wine): the maximum glucose excursion after lunch was 2.76 +/- 0.9 mmol/L at T120 for placebo and 1.97 +/- 0.9 mmol/L at T90 for tannic acid (P < .01); no difference in glucose and insulin excursion was observed between water and ethanol. No interaction between tannic acid and starch was observed in the in vitro experiments, although after preincubation of alpha-amylase with tannic acid, digestion was slowed in a dose-dependent manner (6.1 +/- 1.1 minutes for 0.25 mg tannic acid and 13.1 +/- 1.59 minutes for 1 mg tannic acid). Drinking red wine with a meal did not increase blood glucose in NIDDM patients, and led to a slight decrease in some instances. The effect appeared to be mediated by the nonalcoholic compounds in wine such as tannic acid. Ethanol itself had no effect on plasma glucose or insulin levels.

Intention-to-Treat vs. On-Treatment Analyses of Clinical Trial Data: Experience from a Study of Pyrimethamine in the Primary Prophylaxis of Toxoplasmosis in HIV-Infected Patients

Randomized clinical trials analyzed by the intent-to-treat approach provide unbiased comparisons among treatment groups. To avoid dilution of treatment effect, many people also perform an analysis by treatment actually received, although this method may introduce bias into the results. This paper presents several approaches used for analyzing data of a recent trial and the difficulties encountered in interpreting the results of each approach. The ANRS 005/ACTG 154 Study was a double-blind, placebo-controlled, randomized, international (French, U.S., and Spanish) multicenter trial designed to assess the effectiveness of pyrimethamine for the primary prophylaxis of cerebral toxoplasmosis (CT) in HIV-infected patients with advanced immunodeficiency. In the intention-to-treat analysis, the cumulative probability of CT at 1 year did not differ significantly between the pyrimethamine arm (11.9%) and the placebo arm (13.1%), Hazard Ratio (HR) = 0.94 (95% Confidence Interval (CI) = 0.62-1.42), whereas an on-treatment analysis resulted in a significant difference: 4.2% in the pyrimethamine arm and 12.4% in the placebo arm, HR = 0.44 (95% CI = 0.24-0.80). The data showed a significant interaction between compliance and treatment outcome; and side effects were more frequently cited as reasons for compliance violations in the pyrimethamine group. Several different analytic approaches (censoring data at the time patients discontinued the study medication only for selected reasons) failed to explain the disparity between the estimation of effect of pyrimethamine by the intention-to-treat and on-treatment analyses. This experience led us to believe that comparing the results of both analyses was the best method to convince clinicians that intention-to-treat was the only interpretable analysis. We were concerned that even if pyrimethamine had a beneficial effect, it was very difficult (1) to quantify and (2) to apply to clinical practice unless one could predict the occurrence of study drug discontinuation for each patient at the time of treatment assignment. Although exploratory analyses may yield clinically relevant information and useful clarifications in the evaluation of treatments, intention-to-treat remains the only interpretable analysis of clinical trials.

Short-Term Effect of Red Wine (Consumed During Meals) on Insulin Requirement and Glucose Tolerance in Diabetic Patients

Objectives To determine the effect of wine on insulin requirement or glucose tolerance. Research Design and Methods Five men with insulin-treated diabetes and 10 men with non-insulin-treated diabetes ate the same lunch with the same volume of either water or red wine (2 glasses). Insulin requirement was determined with an artificial pancreas (Biostator). Glucose tolerance was evaluated from the postprandial glycemic level. Results There was no significant difference in insulin requirement determined with an artificial pancreas in the insulin-treated patients after the two meals (31.5 ± 4.21 U with water and 31.8 ± 4.3 U with wine). Glucose tolerance in the non-insulin-treated patients was lower after the meal with wine. Conclusions Moderate prandial wine consumption has no adverse effect on the glycemic control of diabetic patients. Thus, it appears unnecessary to proscribe the consumption of red wine in moderation with meals to diabetic patients. Wine contains tannins and phytates that can explain its action.

Aspects épidémiologiques, cliniques, biologiques et évolutifs de la leptospirose : à propos de 30 observations recueillies en Aquitaine

Thirty cases of leptospirosis serologically proved, are reviewed: contaminating circonstances were often determined. We observed mainly: acute fever, myalgia, jaundice, hemorrhages and acute renal failure (7 hemodialysis). Two patients died (acute respiratory failure, meningo-encephalitis with hemoptysis).

Survival After Aids-defining Events in Patients With<200 Lymphocytes Cd4+ × 106/l Who Are Toxoplasmosis Antibody Positive

The objective of this study was to assess whether patients with CD4+ cell counts <200 x 10(6)/L have a decreased survival after the occurrence of any AIDS-defining event; 187 patients from the placebo arm of a clinical trial of toxoplasmosis prophylaxis (ANRS005-ACTG154) were included. For this analysis, patients were HIV infected without any AIDS-defining event, had a CD4+ lymphocyte count < 200 x 10(6)/L, had a positive serology for Toxoplasma gondii, and had no severe liver, renal, or hematologic abnormalities. We used proportional hazards regression to study the relationships between baseline variables. AIDS-defining events as time-dependent variables, and survival. The risk of dying was increased by 1.9 for a 10-year increase in age and by 1.3 when CD4+ decreased by 50 x 10(6)/L; after the occurrence of a pneumocystosis, a cytomegalovirus infection, or a toxoplasmosis, the risk of dying was multiplied, respectively, by 10.9 (3.0-40.2), 10.0 (2.8-35.4), and 10.0 (4.5-22.2). None of the other AIDS-defining events was associated with an increased risk of dying, but the power to detect such an association was limited. We conclude that the occurrence of pneumocystosis, cytomegalovirus infection, or toxoplasmosis; age; and CD4+ cell count are important determinants of survival for HIV1-infected patients with CD4+ counts < 200 x 10(6)/L who are toxoplasmosis antibody positive.

Manifestations neurologiques de la maladie de Lyme. A propos de 22 cas.

The main clinical and biological features of 22 cases of neurological forms of Lyme disease are reviewed. Radiculitis (n = 15), cranial nevritis (n = 7), meningitis (n = 5) and encephalitis (n = 4) are often associated. Tick bites were previously noticed in only 40% of cases; erythema chronicum migrans in 73%, “one to six months before the onset of neurological symptoms”. Titers of Borrelia Burgdorferi antibodies were always above 1/256. Among 18 patients, DR W2 HLA haplotype was present in 15.

Prévention primaire de la toxoplasmose cérébrale chez le sujet infecté par le VIH: résultats d'un essai randomisé en double insu, pyriméthamine versus placebo

To assess the efficacy of pyrimethamine (Pyr) for primary prophylaxis of cerebral toxoplasmosis (CT) in HIV patients (pts), 554 pts were randomized in a double-blind, placebo-controlled trial (mean follow-up: 14 months). The intent-to-treat analysis found no significant difference in the incidence of ct at 1 year: 12% (Pyr) versus 13% (Pcb) nor in survival. Side-effects leading to stop the study drug were more frequent in Pyr group, especially cutaneous rashes: 8% (Pyr) versus 2% (Pcb).

Ischémie aiguë de jambe révélatrice d'une endocardite à Kingella indologenes

Kingella indologenes is a normal commensal of the upper respiratory tract. It is a gram negative bacillus which does not grow readily on the usual media. The authors report here the second case of K. indologenes endocarditis known in the literature.

La leishmaniose viscérale chez le sujet VIH négatif. Étude de deux observations

Visceral leihmaniasis occurs frequently during HIV infection. Thus, this zoonosis can be encountered in nonimmunocompromised patients. We report 2 cases.