Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p <0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-α blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients.

Elucidation of the kinetics of exposure of neutralizing epitopes on the envelope of human immunodeficiency virus type 1 (HIV-1) during the course of infection may provide key information about how HIV escapes the immune system or why its envelope is such a poor immunogen to induce broadly efficient neutralizing antibodies. We analyzed the kinetics of exposure of the epitopes corresponding to the broadly neutralizing human monoclonal antibodies immunoglobulin G1b12 (IgG1b12), 2G12, and 2F5 at the quasispecies level during infection. We studied the antigenicity and sequences of 94 full-length envelope clones present during primary infection and at least 4 years later in four HIV-1 clade B-infected patients. No or only minor exposure differences were observed for the 2F5 and IgG1b12 epitopes between the early and late clones. Conversely, the envelope glycoproteins of the HIV-1 quasispecies present during primary infection did not expose the 2G12 neutralizing epitope, unlike those present after several years in three of the four patients. Sequence analysis revealed major differences at potential N-linked glycosylation sites between early and late clones, particularly at positions known to be important for 2G12 binding. Our study, in natural mutants, confirms that the glycosylation sites N295, N332, and N392 are essential for 2G12 binding. This study demonstrates the relationship between the evolving "glycan shield " of HIV and the kinetics of exposure of the 2G12 epitope during the course of natural infection.Until recently, it was thought that low levels of neutralizing antibodies to autologous viruses develop slowly throughout human immunodeficiency virus type 1 (HIV-1) infection (6,7,26,27,36). However, two recent studies based on elegant recombinant virus assays provided major new information about the kinetics of the neutralizing antibody response to HIV (39,49). It is now clear that the autologous neutralizing response is generally strong and develops rapidly. However, the neutralizing antibody response exerts a selective pressure that continuously drives the evolution of neutralizing escape mutants, allowing them to persist in the host. This strong, early autologous neutralizing response is generally inefficient against heterologous viruses (39, 49). Broadly neutralizing antibodies, which are able to neutralize a broad spectrum of primary isolates, are rarely found in HIV-1-infected individuals (3,7,26). When detected, they appear late, at least several years after primary infection, mainly in long-term asymptomatic patients (11, 52). A few human monoclonal antibodies (MAbs) with broadly neutralizing activities have been isolated from such individuals (8,12,13,14,25,28,29,45,47,48). Among them, three major MAbs have been characterized in depth: immunoglobulin G1b12 (IgG1b12), 2G12, and 2F5. The epitopes recognized by IgG1b12 and 2G12 are located on the surface envelope glycoprotein gp120. IgG1b12 binds to an epitope overlapping the CD4 receptor site (32,40,43,53), whereas 2G12 binds to a carbohydrate-dependen...

A polymerase chain reaction (PCR) assay for the detection of Epstein-Barr virus (EBV) sequences in various clinical samples, especially peripheral blood leukocytes (PBL) and serum, was carried out and the results obtained were compared with specific EBV serology. One hundred seventy patients were enrolled in the study: 89 healthy blood donors, 22 asymptomatic patients, 36 individuals with primary EBV infection (including 19 patients with infectious mononucleosis [IM]), 22 HIV-infected subjects (including 4 with hairy oral leukoplakia, 3 with central nervous disorders, and 15 with non-Hodgkin's lymphoma). All the serum samples from the healthy blood donors were negative. In patients with IM and in AIDS-non Hodgkin's lymphoma (ARNHL), PCR was strongly positive in leukocytes (> 2,000 genome equivalents/10(4) cells), which was correlated with detectable amounts of EBV DNA in serum. The overall positivity rate of PCR in serum was 58.8%, 68%, and 73% of cases for non-IM primary EBV infections, IM, and ARNHL, respectively. In two cases of EBV primary infection, the viral DNA was detected in serum, respectively 1 month and 2 months before IgM positivity and IgG rise. In one case of ARNHL followed up for several months, PCR (viral load of 2,000 genome equivalents/10(4) cells) became positive concurrently with appearance of lymphoma. In immunocompromised individuals, PCR EBV, if carried out in larger prospective studies, could be considered as a tumor marker, useful for predicting EBV-driven lymphoma and follow-up therapy.

The incidence of severe falciparum malaria is increasing in the developed countries and mortality remains high despite progress in intensive care management and schizonticide treatment. Many authors emphasize the importance of exchange transfusion (EXT) in the most severe cases. We studied 21 cases (34 +/- 12 years, 6 females; SAPS: 8.4 +/- 3.7) of severe malaria (according to WHO criteria) consecutively admitted to ICU between 1985 and 1990: 3 patients underwent EXT. Twenty were febrile above 39 degrees C, 10 had cerebral malaria, 14 hepatic impairment, 8 acute renal failure, 5 pulmonary oedema. Nine patients required mechanical ventilation, 1 haemodialysis, 1 intracranial pressure monitoring. Mean parasitemia was 13%, 16 patients had thrombocytopenia less than 50 x 10(9)/l, 3 anemia less than 7 g/dl and 3 leucopenia less than 2.8 x 10(9)/l. Nineteen received quinine i.v., 1 mefloquine, 1 chloroquine. Sixteen patients received blood products transfusion, 3 were treated by EXT in addition. Twenty were cured and discharged from hospital without sequelae (mean stay: 14 days); 4 had nosocomial infection, 1 a splenic infarction. One patient (17-years-old; SAPS: 17; parasitemia: 7.8%) died 12 h after admission from non-cardiogenic pulmonary oedema with multi-organ failure. The literature and this study lead us to propose EXT in patients with unfavourable evolution after conventional treatment rather than in all the patients with a parasitemia above 10% at admission. A randomized study to compare conventional treatment in ICU with or without EXT is necessary.

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