Surveillance case definition for AIDS in resource-poor countries.
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Biomedical subjects
Publications and source records attributed to C M Farber.
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OBJECTIVE: To evaluate the clinical axis of the World Health Organization (WHO) clinical staging system and the modified WHO staging system proposed by Montaner et al. using the lymphocyte strata > 1500, 1500-1000 and < 1000 cells x 10(6)/l. DESIGN: Cross-sectional study. PATIENTS: Four hundred and fifteen consecutive patients with HIV infection attending three HIV reference centres in Belgium. METHODS: Absolute CD4 lymphocyte counts were compared between stages within the two staging systems. RESULTS: Median CD4 lymphocyte counts decreased with increasing stage of disease in both staging systems. Differences in median CD4 lymphocyte counts between stages of each staging system were statistically significant (Kruskal-Wallis one-way analysis of variance, P < 0.001). The WHO clinical stage 1 and the modified WHO stage I had positive predictive values of 56 and 58%, respectively, for identifying patients with CD4 lymphocyte levels > 500 cells x 10(6)/l. The WHO clinical stage 4 and the modified WHO stage IV had positive predictive values of 79 and 80%, respectively, for identifying patients with CD4 lymphocyte levels < 200 cells x 10(6)/l. CONCLUSIONS: The WHO clinical staging system or a modified version of this system using lymphocytes stratification may be a good alternative in developing countries to the CD4 lymphocyte count-based HIV staging system used in the developed world. Cohort studies in developing countries are needed to assess their prognostic value.
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Glutathione (GSH) content may be the major determinant of a cell's sensitivity to cytotoxic alkylating agents. In the present study, the GSH concentration was determined in lymphocytes isolated from the blood of normal subjects and patients with chronic lymphocytic leukemia (CLL). Comparable levels were found in both types of cells. Incubation for 20 hours led to a decrease in GSH to 51% of baseline values in CLL B cells. Under the same conditions, normal B- or T-lymphocyte GSH content remained constant. GSH depletion was shown to be a characteristic of the B-CLL B lymphocyte. It was not found in the T cells of patients with B-CLL or in cells from patients with T-CLL. Chlorambucil (CLB) contributes to the decrease in GSH in B-CLL lymphocytes; after incubation with the drug, lower levels of GSH were found than in the normal B or T lymphocytes, B-CLL T cells, or T-CLL (CD4 or CD8) cells. GSH depletion of CLL B lymphocytes may be related to the greater therapeutic efficacy of CLB in B-CLL than in T-CLL.
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The specific IgG response induced by BCG vaccination was investigated in 27 adults using two purified BCG antigens in a dot immunoblotting assay. The reflectance values increased significantly after vaccination when P64 but not when P32 was used as the antigen. The values measured after vaccination were compared with those obtained when testing sera from patients with tuberculosis. We observed that the level of anti-P64 IgG reached after BCG immunization was high enough to preclude a serological differential diagnosis with tuberculosis.
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Antimycobacterial IgG levels were measured repeatedly during treatment in 12 patients with moderate or severe pulmonary tuberculous disease using a dot immunobinding assay. We used reflectance densitometry equipment to quantify the immunoperoxidase staining and a Mycobacterium bovis BCG culture filtrate and the purified P32 protein as antigens. Antibody response against whole culture filtrate and P32 antigen increased after a three-month period of treatment. After this antibiotherapy was completed, the estimated amount of antibodies directed against the P32 decreased while those against the whole culture filtrate remained at the same level. A serologic test using P32 as the antigen seems to allow a better discrimination between active and healed tuberculosis.
We devised an immunoassay for the detection of mycobacterial antigens in cell lysates and in tissue extracts which is based on the agglutination of latex particles coated with anti-Mycobacterium bovis F(ab')2, followed by counting of non-agglutinated particles. Mycobacterium bovis cell lysates were tested and a reference curve was established, having a lower limit of detection of 15-20 Mycobacteria. We were able to detect mycobacterial antigens in cell lysates from bronchoalveolar washings and in spleen and liver lysates obtained from experimentally infected rabbits. Antigens were also detected in ten out of 11 samples obtained from patients with proven tuberculous infection. These samples were readily distinguished from 32 negative control samples after pepsin treatment. In contrast, periodate treatment of samples to destroy carbohydrate, abolished all reactivity. Following gel filtration chromatography we identified three peaks with antigenic properties in samples of all types. The detection of mycobacterial carbohydrate antigens by latex agglutination and particle counting should be a useful adjunct in the diagnosis of tuberculosis.
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We devised a dot blot assay to evaluate the IgG and IgA response to P32, a recently isolated antigen specific to mycobacteria. Pleural fluids and the corresponding sera were tested, obtained from five patients with pleural tuberculosis proven by direct examination and/or culture and from 14 patients with pleural effusions of other origins. We measured the total IgG and IgA levels in all samples and determined the anti-P32 titer after adjusting IgG and IgA respectively to the same levels in all samples. Those pleural fluids and sera from tuberculous patients contained a higher proportion of anti-P32 antibodies than samples obtained from nontuberculous control subjects; in those patients, the proportion of anti-P32 antibodies was generally higher in pleural effusion fluid than in serum.
The M13 bacteriophage probe, which makes possible the establishment of DNA fingerprints, was used to study a phenotypically normal woman with a 46XY karyotype and her twin brother. Identical fingerprints and positive hybridization with a series of Y-specific probes were obtained on blood samples from the siblings. DNA from a skin biopsy of the woman yielded a clearly different pattern and displayed no Y-specific hybridization, indicating that she is a spontaneous chimera. This study illustrates the use of DNA fingerprinting as a powerful and simple aid to the diagnosis of natural chimerism.
We report a series of thirteen patients with nervous system complications out of a total of thirty AIDS patients admitted to our hospital over the last two years for which CT and/or MRI have been performed. Five were homosexual men and eight patients (5 men, 3 women) were of African origin (Zaïre and Rwanda) (n = 5) or had had sexual intercourse with the local African population (n = 3). The nervous system complications encountered included: toxoplasma gondii brain abscess (2 patients); cryptococcus neoformans meningitis + toxoplasmosis (1 patient); toxoplasmosis + lymphoma (2 patients); progressive multifocal leucoencephalopathy (1 patient); lymphocytic meningitis or encephalitis (3 patients); lymphoma (1 patient); polyradiculoneuritis (3 patients). Three of thirteen patients had multiple intracranial abnormalities: one had concomitant intraparenchymal toxoplasma abscess and cryptococcal meningitis; in one patient a lymphoma developed after the successful medical treatment of a toxoplasma abscess; conversely, one patient developed a toxoplasma abscess two years after mediastinal radiotherapy for a systemic non-Hodgkin lymphoma. In conclusion, in our experience, nervous system toxoplasmosis is the most frequent AIDS related CNS complication. Our series demonstrates the high frequency of a second neurological disease occurring either concomitantly or separately. In these cases, while CT may readily identify the intracranial abnormalities, it contributes little towards an etiological diagnosis. Finally, our series illustrates the importance of a central African endemic focus for AIDS.
We report five cases of severe pulmonary tuberculosis admitted to hospital with a suspicion of meningeal involvement. The diagnosis of tuberculous meningitis was confirmed by standard bacteriological techniques in two of the five patients. Specific IgG class antibodies directed against the recently purified BCG antigen P32 were detected by a dot immunoblotting technique in the serum and in the cerebrospinal fluid of each patient; however, a higher anti-P32 immunoglobulins/total immunoglobulins ratio was observed in the cerebrospinal fluid of patients with tuberculous meningitis than in their serum while the reverse situation was observed in the other patients.
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The activities of several enzymes that protect against oxidative injury were determined in blood lymphocytes from patients with B chronic lymphocytic leukaemia (CLL) and from normal subjects. Similar glutathione reductase (GR), catalase and glucose-6-phosphate dehydrogenase (G6PD) activities were found in normal and CLL lymphocytes. Higher glutathione peroxidase (GP) activity was found in CLL lymphocytes. This activity in CLL B lymphocytes was 2-fold higher than that of normal B lymphocytes, and 3-fold higher than that of T lymphocytes from either source. Several disease processes have been associated with decreased glutathione peroxidase activity. Our finding with CLL B lymphocytes is believed to be the first example of an increased GP activity in a disease. It may reflect either the expansion of a rare type of B cell population or be an expression of the malignant process.
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A simple dot immunobinding (dot blot) assay procedure has been developed for the detection of antibodies directed against a soluble mycobacterial antigen preparation. This technique was compared with the widely used ELISA, in a study of samples from tuberculous patients. Dot blots were read on a densitometer. The correlation between both assays was excellent (r = 0.91; P less than 0.001); 90% of sera from tuberculous patients were detected using both techniques and a serial two-fold dilution method. Assessments of the end-points of titration curves by reflectometry and simple visual interpretation gave similar results. The dot blot assay is easier to perform and appears to be a practical alternative to ELISA for the detection of anti-mycobacterial antibodies in tuberculous patients.