Cerebral Toxoplasmosis and Lymphoma in Patients with Acquired Immunodeficiency Syndrome

16 Patients with central nervous system (CNS) complications of the acquired immunodeficiency syndrome (AIDS) are described. All patients were male homosexuals. The most common demonstrable lesion in the parenchyma was toxoplasmosis, which produced an area of focal oedema, usually containing a central zone of nodular or ring-shaped enhancement. Cerebral atrophy was also a common finding. One patient had diffuse peri-ventricular lymphomatous infiltration, and a further two patients had both cerebral toxoplasmosis and lymphoma. A delayed “double dose” contrast examination appears to be the most accurate method of outlining the total extent of CNS disease in these patients.     

Cerebral toxoplasmosis in a patient with acquired immunodeficiency syndrome

Patients suffering from acquired immunodeficiency syndrome (AIDS) are being encountered more and more frequently. Because of their immunosuppressed state, they often present with opportunistic infections of the cerebrum. Herein, the case of a patient with AIDS who had cerebral toxoplasmosis is reported. Although the computed tomographic features are nonspecific for cerebral toxoplasmosis, they are interesting because of the considerable variation in type of enhancement and extent of lesions revealed by injection of contrast medium.     

Gastroduodenal Complications in Patients with Adult T-Cell Leukemia

Gastroduodenal endoscopic examinations were performed on 15patients with adult T-cell leukemia (ATL). Twelve had the diseasein acute form, two in chronic form and one patient was in crisis.Eight patients had gastroduodenal lesions, four esophageal candidiasis,three gastric infiltration and two duodenal ATL-cell infiltration.Four out of the five patients who had the gastroduodenal ATL-cellinfiltration complained of gastroduodenal symptoms such as anorexia,upper abdominal pain, diarrhea and melena. Our observationssuggested that these gastroduodenal symptoms were related tothe gastroduodenal ATL-cell infiltration. Esophageal candidiasisin ATL could be related to immunodeficiency.     

Antibody response to Pneumocystis jirovecii major surface glycoprotein

We conducted a prospective pilot study of the serologic responses to overlapping recombinant fragments of the Pneumocystis jirovecii major surface glycoprotein (Msg) in HIV-infected patients with pneumonia due to P. jirovecii and other causes. Similar baseline geometric mean antibody levels to the fragments measured by an ELISA were found in both groups. Serum antibodies to MsgC in P. jirovecii patients rose to a peak level 3-4 weeks (p<0.001) after recovery from pneumocystosis; baseline CD4+ count > or =50 cells/microL and first episode of pneumocystosis were the principal host factors associated with this rise (both p<0.001). Thus, MsgC shows promise as a serologic reagent and should be tested further in clinical and epidemiologic studies.     

Epstein-Barr Virus load and immune activation in Human Immunodeficiency Virus type 1-infected patients

Background

Patients infected with HIV-1 are at high risk of developing Epstein-Barr Virus (EBV)-related diseases. Chronic immune activation is a hallmark of HIV-1 pathogenesis and may play a role in B-cell stimulation and expansion of EBV-infected cells.

Objectives

The aim of the study was to define the relationship between parameters of immune activation and EBV load in HIV-1-infected subjects.

Study design

A total of 156 HIV-1-infected patients were studied. EBV types 1 and 2 were quantified on peripheral blood mononuclear cells by multiplex real-time PCR. Plasma levels of cytokines and lipopolysaccharide (LPS) were determined by immunoenzymatic assays. B-cell activation was analyzed by flow cytometry.

Results

EBV-DNA was detected in 114 patients, and in all but 3 was EBV type 1. The median [interquartile] EBV-DNA load was 43[1-151] copies/10⁵ PBMC. EBV-DNA load was higher in patients with detectable HIV-1 plasma viremia, despite good immunological status (CD4 > 500 cells/μl), than in patients with undetectable HIV-1 plasma viremia regardless of immunological status (46[5-136] copies/10⁵ cells vs 17[1-56] copies/10⁵ cells, p = 0.008). Patients with high EBV-DNA load (>median value) had higher levels of LPS and proinflammatory cytokines (IL-6, IL-10 and TNF-α) than patients with low EBV load. Furthermore, percentages of activated B-cells correlated with EBV-DNA load (r_s = 0.754; p < 0.001).

Conclusions

Overall, these findings indicate a strong association between HIV-1 viremia, markers of immune activation and EBV load and suggest that persistence of HIV-1 viremia and immune activation, regardless of peripheral CD4 cell depletion/repopulation, may favor expansion of EBV-infected cells and onset of EBV-related malignancies.     

SIVagm containing the SHIV89.6P Envelope gene replicates poorly and is non-pathogenic

SIVagm does not induce disease in its African green monkey (AGM) host. In comparison, the hybrid simian-human immunodeficiency virus SHIV89.6P that carries the HIV env gene induces disease in rhesus macaques more rapidly than the SIVmac parent virus. To address the possibility that this enhancement of disease by HIV env would also occur when present in SIVagm, a full-length SIVagm/89.6Penv chimeric lentivirus genome (termed SHIV-MP) was constructed. SHIV-MP replicated similarly to SIVagm in simian peripheral blood mononuclear cells (PBMCs). In inoculated AGMs, rhesus macaques and pig-tailed (PT) macaques the absolute number of CD4⁺ T lymphocytes remained at normal levels. The peak levels of productively infected cells in SHIV-MP-infected monkeys ranged from 10¹ to 10² per 10⁶ PBMCs, while in SIVagm infected macaques the levels were 10-100-fold higher. The env gene of SHIV89.6P therefore appears insufficient to confer acute pathogenicity to a non-pathogenic primate lentivirus due to poor in vivo replication.     

Cell mediated immunity to meet the avian influenza A (H5N1) challenge

Avian influenza A subtype H5N1 virus with its recombination potential with the human influenza viruses presents a threat of producing a pandemic. The consensus is that the occurrence of such a pandemic is only a matter of time. This is of great concern, since no effective vaccine is available or can be made before the occurrence of the event. We present arguments for the use of cell mediated immunity for the prevention of the infection as well as for the treatment of infected patients. Transfer factor (TF), an immunomodulator of low molecular weight capable of transferring antigen-specific cell mediated immune information to T-lymphocytes, has been used successfully over the past quarter of a century for treating viral, parasitic, and fungal infections, as well as immunodeficiencies, neoplasias, allergies and autoimmune diseases. Moreover, several observations suggest that it can be utilised for prevention, transferring immunity prior to infection. Because it is derived from lymphocytes of immune donors, it has the potential to answer the challenge of unknown or ill-defined pathogens. Indeed, it is possible to obtain an antigen-specific TF preparation to a new pathogen before its identification. Thus, a specific TF to a new influenza virus can be made swiftly and used for prevention as well as for the treatment of infected patients.     

Chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection

BACKGROUND: Alcohol abuse has been reported to have a high prevalence in the human immunodeficiency virus (HIV)-infected population. However, its impact on disease progression is unknown. Studies dissecting the drug-induced or alcohol-induced metabolic derangements that are likely to alter the course of disease progression are lacking. This is particularly important because of the substantial reduction in morbidity and mortality of patients on highly active antiretroviral therapy (HAART). HIV infection has become a more chronic disease during which alcohol-induced metabolic alterations may become more prevalent and pronounced. METHODS: The present study used a model of chronic intragastric alcohol administration initiated 3 months before intravenous simian immunodeficiency (SIV) inoculation and continued thereafter throughout the course of SIV infection, to investigate the impact of chronic alcohol binge-like consumption during the initial 10-month asymptomatic phase of SIV infection in nonhuman primate rhesus macaques. Anthropometric, metabolic, biochemical, nutritional, and immune state indicators were examined before infection and at 3-month intervals in asymptomatic chronic alcohol-treated SIV-infected macaques and time-matched isocaloric and uninfected controls. RESULTS: Intravenous SIV(DeltaB670) infection resulted in increased viral load, decreased circulating CD4(+)/CD8(+) lymphocyte ratio, and increased lymphocyte proliferation (Ki67/CD3(+)). Chronic alcohol/SIV(+) animals showed a higher viral load at 3 months post-SIV infection as well as a significant and early decrease in caloric intake and nitrogen balance associated with a change in food choice. Rates of skeletal muscle protein synthesis and breakdown, mRNA expression of IGF-I, myostatin, or the ubiquitin ligase muscle atrophy F-box protein (MAFbx) did not differ from basal during the 10-month asymptomatic period of infection. However, muscle TNF-alpha mRNA expression was markedly increased at 10 months post-SIV infection in alcohol/SIV(+) animals. DISCUSSION: These findings suggest that chronic alcohol accelerates nutritional and metabolic dysregulation during SIV infection and may favor a skeletal muscle proinflammatory state, possibly conducive to subsequent muscle wasting.     

Progressive multifocal leukoencephalopathy in an HTLV-I carrier

This report describes a previously 28-year-old healthy woman, identified as an asymptomatic human T-lymphotropic virus type I (HTLV-I) carrier, who developed both progressive multifocal leukoencephalopathy (PML) and Pneumocystis jiroveci pneumonia. For diagnostic confirmation of PML, stereotactic brain biopsy demonstrated multiple demyelinating lesions with the presence of JC viral antigen. Intramuscular alpha-interferon therapy for 2 weeks brought considerable neurologic improvement. Three years later, the patient developed lymphoma-type of adult T-cell leukemia, suggesting that HTLV-I carrier might be one of the underlying diseases of PML.