Disease In AIDS Patients Research Articles

Role of antigenemia assay in the early diagnosis and prediction of human cytomegalovirus organ involvement in AIDS patients.

The role of an antigenemia assay in the diagnosis and prediction of human cytomegalovirus (HCMV) disease in AIDS patients was evaluated. The clinical history of 62 patients with advanced HIV infection from whom a total of 248 blood samples were drawn and tested by the HCMV antigenemia assay was examined retrospectively. Between December 1992 and January 1994, 28 episodes of HCMV disease with organ involvement were recorded; the antigenemia assay was positive in 23 of them (82.1%). In particular, this test was positive in 11 of 12 (91.6%) first episodes and in 3 of 3 (100%) recurrent episodes occurring in patients not receiving maintenance therapy. The same test was positive in 9 of 13 (69.2%) recurrent episodes occurring in patients receiving maintenance therapy. The first occurrence of HCMV disease was always preceded by a positive antigenemia assay 2 and 4 months before diagnosis (in all 7 patients of the 7 for whom a blood sample was available before HCMV disease). A positive antigenemia test result was not always followed by organ involvement, but a high positive cell count (> 100/200,000 polymorphonuclear leukocytes) strongly correlated with the appearance of HCMV disease in the following 1 to 3 months (100% of cases). The antigenemia assay is a useful and reliable indirect method for the diagnosis and prediction of HCMV end-organ disease in severely and persistently immunocompromised AIDS patients.

Current status of human cytomegalovirus disease

Human cytomegalovirus (HCMV) can establish lifelong persistence after primary infection with reactivation occurring as a result of immunosuppression. There is much evidence that molecular interactions between the immune system and the HCMV are responsible for immune escape. HCMV in many cells especially in mononuclear blood cells during latency are frequently the source of transmission and spreading and results in a variety of disorders. In this review some data about acute infection in immunocompetent host (mononucleosis, hepatitis), about intrauterine HCMV infection, about infection and endogenous reinfection in bone marrow and solid organ transplant recipients (pneumonitis) and about HCMV disease in AIDS patients (encephalitis, neuropathy, retinitis, colitis) are investigated. Moreover, HCMV associated vasculitis is described in patients with myocarditis, rheumatoid arthritis or polyradiculopathy. HCMV could play an important role in atherosclerosis. Several types of human malignancy have been linked to HCMV and it has been shown that HCMV ie genes upregulate expression of cellular oncogenes. The diagnosis of HCMV infection is carried out by viremia in cell culture using immediate early antigen staining, by antigenaemia which appears to be an early quantitative and predictive tool, by HCMV DNA detection using hybridization and PCR, and by IgM and IgG antibody evaluation. Two antiviral drugs are used for treatment: ganciclovir and phosphonoformic acid; few resistant clinical isolates have been reported. Specific gammaglobulin activity is discussed. HCMV vaccine is not available.

Mycobacterial infections in AIDS patients; Lorraine, France⋆

AbstractObjectives Description of the epidemiology of mycobacterial infections in HIV/AIDS patients in Nancy. Comparison of the main features of tuberculous and non‐tuberculous mycobacterial infections.Patients 58 HIV‐positive patients with mycobacterial infections attended the Department of Infectious Diseases, University Hospital of Nancy from January 1985 to December 1992.Results Tuberculosis identified in 17 patients who were only moderately immunosuppressed, and had a high fatality rate (65%): no resistant strains isolated. Non‐tuberculous mycobacteria infections occurred in 41 patients who were deeply immunosuppressed and had a poor prognosis. Mycobacterium avium‐intracellulare complex was the most frequently isolated species (31 cases) and showed a high level of antibiotic resistance.Conclusions NTM infections are life‐threatening diseases in AIDS patients and should be systematically sought in HIV‐positive patients with low CD4 + lymphocyte count.

Mycobacterial infections in AIDS patients; Lorraine, France

Objectives Description of the epidemiology of mycobacterial infections in HIV/AIDS patients in Nancy. Comparison of the main features of tuberculous and non-tuberculous mycobacterial infections.Patients 58 HIV-positive patients with mycobacterial infections attended the Department of Infectious Diseases, University Hospital of Nancy from January 1985 to December 1992.Results Tuberculosis identified in 17 patients who were only moderately immunosuppressed, and had a high fatality rate (65%): no resistant strains isolated. Non-tuberculous mycobacteria (NTM) infections occurred in 41 patients who were deeply immunosuppressed and had a poor prognosis. Mycobacterium avium-intracellulare complex was the most frequently isolated species (31 cases) and showed a high level of antibiotic resistance.Conclusions NTM infections are life-threatening diseases in AIDS patients and should be systematically sought in HIV-positive patients with low CD4 + lymphocyte count.

High-Dose Fluconazole for Treatment of Cryptococcal Disease in Patients with Human Immunodeficiency Virus Infection

Eight patients (6, cryptococcal meningitis; 2, high-titer cryptococcal antigenemia) were treated with 800 mg/day fluconazole to assess the safety and efficacy of high-dose fluconazole as primary therapy. Five patients with meningitis had resolution of clinical symptoms and all 6 had negative cerebrospinal fluid (CSF) cultures by day 82 (median, 21 days). One meningitis patient developed neurologic deterioration and was switched to amphotericin B at day 18, but CSF culture was negative on day 15 of fluconazole therapy. In 2 patients with cryptococcal antigenemia, clinical symptoms resolved and serum antigen titers declined rapidly; they did not progress to meningitis. Therapy was well tolerated, with mainly gastrointestinal side effects. Four patients had mild increases in liver enzymes; another had a threefold increase in alkaline phosphatase. Mean steady-state serum level of fluconazole was 45 +/- 15 micrograms/mL, and paired CSF and serum levels were 40 +/- 14 and 49 +/- 14 micrograms/mL, respectively. High-dose fluconazole appears safe and effective for cryptococcal disease in AIDS patients.

Inhibition of growth Mycobacterium avium in murine and human mononuclear phagocytes by migration inhibitory factor

Infections caused by Mycobacterium avium, the most common form of diseminated bacterial disease in AIDS patients, are difficult to treat because of their resistance to many antimycobacterial drugs. The results of the present study show that recombinant migration inhibitory factor, a 12-kDa molecule recently isolated by COS-1 cell expression screening of cDNA from a human T-cell hybridoma, has potent inhibitory activity on the growth of a panel of clinical isolates of M. avium within both bone-marrow-derived murine macrophages and cultured human blood monocytes. These cells cultured in recombinant migration inhibitory factor exhibit various signs of activation, including cell division, morphological changes such as evidence of substantial phagolysosomal fusion, and enhanced secretion of tumor necrosis factor.

Inhibition of microsporidian spore germination

Microsporidia are obligate intracellular parasites that are increasingly recognized as significant causes of disease in AIDS patients. Gordon Leitch, Govinda Visvesvara and Qing He here describe the deployment of the microsporidian spore infection apparatus, the polar filament, and show how this may be a useful site for chemotherapeutic interdiction of the infections caused by these parasites.

Factors Associated with Increased Risk of Acquiring Cytomegalovirus Disease in AIDS Patients

Factors Associated with Increased Risk of Acquiring Cytomegalovirus Disease in AIDS Patients

Audit of endoscopic surveillance biopsy specimens in HIV positive patients with gastrointestinal symptoms.

An audit of upper gastrointestinal endoscopy in HIV infected patients with gastrointestinal symptoms assessed the frequency of disease detected by endoscopy and routine laboratory analysis of surveillance biopsy specimens. Sixty nine consecutive endoscopies were performed in 59 HIV infected patients. Endoscopic biopsy specimens were taken from the lower oesophagus, gastric antrum, and third part of the duodenum for virology, histopathology, parasitology, bacteriology, and mycobacterial culture. Endoscopic appearances detected disease in 25/59 (42.4%) patients (oesophageal candida, 14; oesophageal ulcer, 3; Kaposi's sarcoma, 4; others, 4), but only 4/43 (9.3%) specimens showed evidence of disease in the absence of endoscopic abnormality. Virology for cytomegalovirus (detection of early antigenic fluorescent foci and culture) was positive in 6/59 (10.2%) patients, but parasitology and mycobacterial culture were negative in all cases. Histopathology was abnormal in 11/52 (21%) oesophageal biopsy specimens, 13/47 (28%) gastric biopsy specimens, and 4/65 (6%) duodenal biopsy specimens. Abnormal findings were found predominantly in those with advanced HIV disease (CDC Stage IV) (21/33 patients (64%)) compared with those with early HIV disease (CDC Stage II) (5/26 (19%)). In conclusion, upper gastrointestinal endoscopy detects macroscopic disease in AIDS patients and those with low CD4 counts, but routine surveillance biopsy specimens of apparently normal bowel in early HIV disease (or where CD4 counts are greater than 0.2 x 10(9)/1) are of little value.

Diagnostic value of amplification of human cytomegalovirus DNA from gastrointestinal biopsies from human immunodeficiency virus-infected patients.

In order to assess the value of human cytomegalovirus (HCMV) DNA amplification of gastrointestinal biopsies, we studied 57 human immunodeficiency virus-infected patients with and without gastrointestinal HCMV diseases. After DNA extraction, a 406-bp fragment from the unique short region of the HCMV genome was amplified by 35 cycles of polymerase chain reaction (PCR) and semiquantified from 80 to 80,000 HCMV genomic copies. Among 12 non-AIDS patients, the PCR assay was negative for 11 of 12 duodenal and 8 of 8 colorectal samples. It was also negative for 28 of 31 duodenal and 12 of 15 colorectal samples from 31 AIDS patients without gastrointestinal HCMV diseases. Among 14 AIDS patients with gastrointestinal HCMV diseases, the PCR assay was positive for 12 of 12 patients with HCMV duodenitis and for 13 of 13 patients with HCMV colitis. Results were dichotomized between high and low HCMV-DNA copy numbers. For duodenitis, sensitivity was 92% and specificity was 100%. For colitis, sensitivity was 92% and specificity was 93%. Specificity and sensitivity were not influenced by shedding status for HCMV or by other gastrointestinal infections. HCMV DNA amplification of gastrointestinal biopsies is a sensitive and specific tool for the diagnosis of gastrointestinal HCMV diseases in AIDS patients.

Retinal disease associated with AIDS.

In recent years an enormous amount of new information in the area of retinitis and retinal disease in immunosuppressed patients has been acquired. There have been exciting new developments in our understanding of the pathogenesis of retinal disease in AIDS patients as well as important advances in the diagnosis and therapy of infectious retinitis. This article will summarise the recent advances in this area and outline the direction of future research as it applies to the clinical management of patients with retinal manifestations of AIDS. Diagnostic and therapeutic difficulties will be addressed including the appropriate selection of antiviral drugs and other therapeutic modalities in patients with sight-threatening retinitis.

Direct interactions of human lymphocytes with the yeast-like organism, Cryptococcus neoformans.

Lymphocytes, especially CD4+ T cells, are essential for clearance of the yeast-like organism Cryptococcus neoformans from the infected host. The mechanism(s) by which the lymphocytes facilitate elimination of cryptococci has not been elucidated. It is generally thought, however, that lymphocytes reactive with C. neoformans indirectly function by production of lymphokines to enhance clearance of the organism by natural effector cells such as macrophages. In the present study, we assessed the ability of freshly isolated human lymphocytes to interact directly with C. neoformans and to limit the growth of the organism in vitro. We found that large granular lymphocytes (LGL) as well as T cells bound to cryptococcal cells when the lymphocytes were mixed with the cryptococcal cells at a 2:1 ratio. The physical binding interactions of the two lymphocyte populations were different. LGL attached to the cryptococcal cells by many microvilli; T lymphocytes associated with the yeast through broad areas of membrane attached to the cryptococcal cell surface. The two types of lymphocyte interactions did not result in phagocytosis but resulted in direct inhibition of cryptococcal growth, making these lymphocyte interactions with cryptococci distinctly different from interactions of monocytes with cryptococci. With the human natural killer (NK) cell line, NK 3.3, we confirmed that NK cells that were present in the LGL population were capable of limiting the growth of C. neoformans. Through immunoelectron microscopy, human CD3+ lymphocytes were seen attached to cryptococcal cells and by mass cytolysis, human CD3+ lymphocytes were shown to be responsible for inhibition of C. neoformans growth. The direct inhibitory interactions of NK cells and T lymphocytes with cryptococcal cells may be important means of host defense against this ubiquitous organism that frequently causes life-threatening disease in AIDS patients.

Inhibition of growth of Mycobacterium avium in murine and human mononuclear phagocytes by migration inhibitory factor.

Infections caused by Mycobacterium avium, the most common form of diseminated bacterial disease in AIDS patients, are difficult to treat because of their resistance to many antimycobacterial drugs. The results of the present study show that recombinant migration inhibitory factor, a 12-kDa molecule recently isolated by COS-1 cell expression screening of cDNA from a human T-cell hybridoma, has potent inhibitory activity on the growth of a panel of clinical isolates of M. avium within both bone-marrow-derived murine macrophages and cultured human blood monocytes. These cells cultured in recombinant migration inhibitory factor exhibit various signs of activation, including cell division, morphological changes such as evidence of substantial phagolysosomal fusion, and enhanced secretion of tumor necrosis factor.

Diagnosis of human cytomegalovirus central nervous system disease in AIDS patients by DNA amplification from cerebrospinal fluid.

The utility of amplification of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid (CSF) for the diagnosis of HCMV central nervous system (CNS) disease in AIDS patients was studied. CSF specimens from 30 patients with neurologic dysfunction were assayed by polymerase chain reaction (PCR), and the results were correlated with histopathologic findings, CSF culture, and clinical manifestations. PCR was positive in all 11 patients who had histopathologic evidence of HCMV CNS disease, including 4 who were CSF culture-negative. Three patients with HCMV polyradiculopathy had CSF positive by PCR. Nine patients negative for HCMV by neuropathologic study and an additional 7 patients with HCMV-unrelated clinical diagnosis were all CSF PCR-negative, despite concomitant systemic HCMV infection in 7. In addition, 24 asymptomatic human immunodeficiency virus-infected individuals were CSF PCR-negative. CSF PCR appears to be a sensitive and specific diagnostic method for detection of HCMV CNS disease in AIDS patients.

Pharmacokinetics of foscarnet after twice-daily administrations for treatment of cytomegalovirus disease in AIDS patients.

The pharmacokinetics of foscarnet were evaluated in 11 AIDS patients with cytomegalovirus disease after twice-daily infusion of 90 mg/kg of body weight for 2 weeks. All patients were hydrated during foscarnet infusion. Blood and urine samples were collected on days 1, 7, and 14 of therapy. Foscarnet concentrations were measured by high-pressure liquid chromatography. Despite large interindividual variations, no significant differences were seen between day 1, day 7, and day 14 concentrations in plasma. Mean peak and trough concentrations on day 14 of therapy were 605 +/- 118 and 52 +/- 59 microM, respectively. In all patients, peak concentrations were well above those necessary to inhibit cytomegalovirus. Pharmacokinetic parameters remained stable throughout the study. On day 14, the mean half-life was 3.4 h, total and renal clearances were 118 and 92 ml/min, respectively, and the volume of distribution was 0.6 liter/kg. These data and previous clinical trials demonstrate that this more convenient dosage regimen can be safely used for patients with cytomegalovirus disease. The side effects were comparable to those reported with other dosage regimens, although no renal impairment was seen in this study, probably because of the hydration.

Ganciclovir with recombinant methionyl human granulocyte colony-stimulating factor for treatment of cytomegalovirus disease in AIDS patients

Ganciclovir with recombinant methionyl human granulocyte colony-stimulating factor for treatment of cytomegalovirus disease in AIDS patients

Modeling all dialogue system participants to generate empathetic responses

A dialogue system between an expert system and its users is described which combines two recent hypothesis, First, that the dialogue system should explicitly model both the person directly interacting with the dialogue system (the agent) and the person reasoned about by the expert system (the patient) in order to communicate meaningfully with both people. Second, that a dialogue system can model the domain-related beliefs, preferences and concerns of both its users and generate responses empathetic to both. This dialogue system is called serum, standing for ‘System for Empathetic Responses with User Models’. serum generates natural-language responses about attribute values of domain objects, via three transformations. First, the system converts properties of the agent and patient, and domain knowledge, into a pragmatic objective like empathy. Second, serum converts the pragmatic objectives into surface structure cues like object emphasis and level of technicality. Finally, serum converts the surface structure cues to realize text that is natural, appropriately technical and emotionally empathetic. serum is demonstrated in describing tests and treatments for lung disease in AIDS patients, a sensitive domain where empathetic responses may be needed.

HIV‐1, macrophages, glial cells, and cytokines in AIDS nervous system disease

Hallmarks of central nervous system (CNS) disease in AIDS patients are headaches, fever, subtle cognitive changes, abnormal reflexes, and ataxia. Dementia and severe sensory and motor dysfunction characterize more severe disease. Autoimmune-like peripheral neuropathies, cerebrovascular disease, and brain tumors are also observed. Histological changes include inflammation, astrocytosis, microglial nodule formation, and diffuse de- or dysmyelination. Focal demyelination can also be seen. It is clear that AIDS-associated neurological diseases are correlated with greater levels of HIV-1 antigen or genome in tissues. In AIDS dementia, macrophages and microglial cells of the CNS are the predominant cell types infected and producing HIV-1. However, manifestations of the disease make it unlikely that direct infection by HIV-1 is responsible. It seems more likely that the effects are mediated through secretion of viral proteins or viral induction of cytokines that bind to glial cells and neurons. HIV-1 induction of such cytokines as interleukin 1 (IL 1) and tumor necrosis factor-alpha (TNF alpha) may lead to an autocrine feedback loop involving further productive virus replication and induction of other cytokines such as interleukin 6 (IL 6) and granulocyte-macrophage colony-stimulating factor (GMCSF). Interleukin 1 and TNF alpha in combination with IL 6 and GMCSF could account for many clinical and histopathological findings in AIDS nervous system diseases. As HIV-1 infected patients produce elevated levels of IL 1, TNF alpha, and IL 6, it will be important to make a formal connection between the presence of these factors in the CNS, which are all products of activated macrophages, astroglia, and microglia, their in vivo induction directly by virus or indirectly by virus-induced intermediates, and the clinical and pathological conditions seen in the nervous system in this disease.

Diagnostic Significance of Apparent Abnormal Bowel Activity on Ga-67 Scans in AIDS Patients

Twenty-one Ga-67 studies on 19 AIDS patients were analyzed to investigate the relationship between clinically acute gastrointestinal disease and abnormal scintigraphic bowel activity. Whole body images were obtained at times ranging from 4 to 192 hours, with most exams imaged at 48 and 72 hours. Abnormal bowel activity was observed in eight of 21 exams. Patients experienced acute GI disease during seven studies. Gallium scan results and clinical presentation agreed in 14 cases; both were abnormal in four and normal in 10. However, four exams showed abnormal activity in asymptomatic patients, while three normal studies were obtained in patients with clinically evident GI disease. Sensitivity was 57% and specificity 71%. Positive predictive value was .50 and negative predictive value .77. All true-positive cases were associated with Mycobacterium avium intracellulare (MAI) infection. This study implies that gallium imaging is unreliable for diagnosing acute bowel disease in AIDS patients, but may suggest a particular pathogen (MAI) in the symptomatic individual.

Découverte de Leishmania infantum dans un liquide de lavage bronchoalvéolaire chez un patient infecté par le VIH

The authors report the finding of Leishmania infantum in a bronchoalveolar lavage in AIDS. This localization has never been reported in the litterature and confirms the unusual expression of the disease in AIDS patients.