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Biomedical subjects

M Schrappe

Publications and source records attributed to M Schrappe.

At least 109 records · Page 6Linked to original sources

Down's syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Münster Group.

Clinical characteristics, treatment response and outcome were evaluated in children with Down's syndrome (DS) and acute lymphoblastic leukemia (ALL) as compared to other children with ALL (NDS). Sixty-one DS and 4049 NDS patients, receiving intensive antileukemic treatment during four consecutive trials (ALL-BFM 81, 83, 86 and 90) of the Berlin-Frankfurt-Münster Group (BFM), were retrospectively analyzed. DS and NDS children did not differ with respect to sex, leukocyte count, CNS leukemia and cytogenetic translocations. The DS cohort was slightly older (P=0.04), presented predominantly with the common while lacking the T immunophenotype (P=0.005), had a lower frequency of hyperdiploidy (P=0.004) and tended to have a better initial steroid response (P=0.057). Therapy-associated morbidity especially during high-dose methotrexate and a subsequent need for treatment modification occurred in 43% of all DS patients. Event-free survival (EFS) was slightly worse in children with DS (58+/-8% vs 70+/-1%, P=0.14), mainly due to rather late bone marrow recurrences. However, EFS in DS patients was comparable to the NDS group once they either received treatment with no major modifications (65+9% vs 70+/-1%, P=0.66) or were <6 years of age, irrespectively of therapy modifications (73+/-9% vs 74+/-1%, P=0.7). Cox regression analysis revealed that DS was an adverse prognostic factor for patients having completed therapy (P=0.0107), but was not prognostic at diagnosis (P=0.103). Age > or = 6 years, suboptimal treatment and infectious problems contributed to the slight inferior EFS in children with ALL and Down's syndrome. Therefore, most of these patients can be successfully treated if receiving intensive antileukemic treatment with no major modifications, but they require more sophisticated management of toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Immunophenotypic and clinical features of T-cell receptor gammadelta+ T-lineage acute lymphoblastic leukaemia.

The immunophenotypic and clinical features of TCR-gammadelta+ T-lineage acute lymphoblastic leukaemia (T-ALL) were prospectively analysed in 52 children with membrane CD3+ T-ALL. We observed a relatively high incidence of TCR-gammadelta+ T-ALL (26/52 patients). Leukaemic blasts from 22 children demonstrated TCR-alphabeta positivity, and simultaneous expression of the TCR-beta and -delta chain was found in four children. Clinical and haematological features of TCR-alphabeta and gammadelta+ T-ALL did not differ significantly, except that haemoglobin levels were significantly lower in TCR-gammadelta+ cases. Event-free survival at 4 years was significantly better in TCR-gammadelta+ compared with TCR-alphabeta+ T-ALL, but expression of TCR molecules did not emerge as an independent prognostic factor in multivariate analysis.

Acute Disease↗

Mutation analysis of CD95 (APO-1/Fas) in childhood B-lineage acute lymphoblastic leukaemia.

The CD95 system plays an important role in lymphocyte homeostasis, has been implicated in the development of lymphoid malignancies, exerts a tumour suppressor function, and contributes to drug-induced cytotoxicity. We hypothesized that mutations of CD95 may occur in childhood B-lineage acute lymphoblastic leukaemia (ALL), a disease known for its constitutive resistance towards CD95-mediated apoptosis. We investigated 32 primary B-lineage ALL of childhood and five B-lineage ALL cell lines. All primary leukaemias expressed CD9 5 and bcl-2 to a variable degree. Most of the leukaemias were resistant towards CD95-mediated apoptosis. However, using SSCP analysis, no mutations in the coding and proximal promoter region could be detected. We conclude that the resistance towards CD95-mediated apoptosis observed in most de novo B-lineage ALL is not caused by mutations of the CD95 death receptor.

Apoptosis↗

Systematic review on the cost-effectiveness of public health interventions for HIV prevention in industrialized countries.

OBJECTIVE: Systematic review on cost-effectiveness of public health interventions for primary HIV-prevention programs. DESIGN: Rating of publications using the guidelines for economic studies in medicine of the British Medical Journal Economic Evaluation Working Party. METHODS: Studies with defined nondrug intervention, defined study population, identifiable method of analysis and at least one endpoint for evaluation of intervention were included. One publication could consist of more than one study. Methods to generate effectiveness data, inclusion of human costs and kind of outcome parameters for economic evaluation were documented. To avoid bias in performing the review, the British Medical Journal guidelines were applied. Cost-effectiveness data were reviewed according to outcome parameters used in economic evaluation. RESULTS: Forty studies were identified in 34 publications, 30/40 from the United States and 22 supported by public funding; only five studies were directed to men who have sex with men, intravenous drug users and persons with HIV-infected partners. Screening programs and counseling with testing accounted for 30/40 studies. Complete research question (intervention and outcome) was presented in 29/40 studies (72.5%). Thirty-four studies were conducted from the societal perspective and the viewpoint was clearly stated in 31/40 studies. Incremental analysis was performed in 21 studies, correction for inflation in two and discounting when appropriate in 23/29 studies; sensitivity analysis was performed in 23/40. Effectiveness data were presented in 38 studies. Diagnosis of previously unknown HIV infection (n = 11), sexual (n = 7) and vertical transmission (n = 6), infection of patients by healthcare workers and life years saved (both n = 6) served as the most common outcome parameters. In 21 studies, human costs were included in the estimation of costs (52.5%) and nine studies used the human capital approach. Cost-effectiveness data revealed costs between US$460 and US$1.2 million per case of previously unknown HIV infection prevented, strongly depending on prevalence. Studies on sexual and vertical transmission demonstrated lower costs when the benefits of treatment were included. Costs for 1 life-year saved varied between $29,000 and $458,000. CONCLUSIONS: The British Medical Journal guidelines for economic analysis in medicine are a feasible instrument for systematic reviews of cost-effectiveness studies on primary HIV infection. The quality of published studies varies widely. A clear definition of outcome parameters as an object of economic evaluation can be regarded as crucial, besides incremental analysis, discounting, and inclusion of human costs. Further work is needed to develop and evaluate a specific rating system for cost-effectiveness analysis in this field.

Cost-Benefit Analysis↗

Polymerase chain reaction for diagnosis and species differentiation of microsporidia.

Polymerase chain reaction (PCR) techniques have been developed for the detection of microsporidian DNA in different biological samples. We used sequence data of the rRNA gene for the identification of Enterocytozoon bieneusi, Encephalitozoon intestinalis, E. cuniculi, and E. hellem in different biological samples of HIV-infected patients by PCR, Southern blot hybridization, restriction endonuclease digestion analysis, cloning, and comparative genetic sequencing. One primer pair was used for amplification of the entire small subunit (SSU)-rRNA gene of E. bieneusi, E. intestinalis, and E. hellem from samples with electron microscopy confirmed infection. The amplified 1.2 kb SSU-rRNA gene fragments were ligated into a pMOSBlue T-vector, transfected into pMOSBlue competent cells, and were used as positive controls. Several primer pairs and hybridization probes were used to amplify and identify microsporidian DNA from different samples. Light microscopical examination of samples was performed in all patients and transmission electron microscopy was done on a subset of patient samples. DNA products were obtained from all samples with confirmed microsporidial infections. The identity of the DNA fragments was determined by Southern blot hybridization or by restriction endonuclease digestion analysis or by DNA sequencing. The results show that PCR is a reliable and sensitive indicator for the presence of microsporidian DNA in different biological samples of HIV-infected patients. PCR can be used further for species differentiation of microsporidia, even between species which cannot be differentiated by light and/or electron microscopy.

Animals↗

[Cystic form of Pneumocystis carinii pneumonia].

BASIC PROBLEM AND OBJECTIVE: In rare instances Pneumocystis carinii pneumonia (PCP) can occur in a cystic form, characterized by an acute course. The correct diagnosis is often missed. An analysis of a large cohort of patients with PCP was undertaken to determine the incidence and clinical manifestations of this form of the disease. PATIENTS AND METHODS: Data on all HIV-positive patients on the hospital registry, hospitalized with the diagnosis of PCP between January 1988 and July 1996, were retrospectively analysed. To be included in the study, PCP had to have been confirmed microscopically on bronchial lavage or histologically by lung biopsy. The chest radiogram and (if available) computed tomogram of these patients were examined for possible cystic changes, and clinical as well as laboratory findings recorded. RESULTS: Five of 180 patients with PCP had cystic changes (2.8%). The interval between first symptoms and diagnosis ranged from 30 to 200 days (median: 32 days). All five patients (age: 24-49 years; all males) had a far advanced immunological disorder (median CD4 count: 10/microliter) and were in stage C3 (Centers for Disease Control). Three of the five patients had prophylactically inhaled pentamidine (300 mg/month). Bronchial lavage was false-negative in three of the five cases. One patient had a spontaneous pneumothorax. Lactate dehydrogenase levels were normal or only slightly elevated (207-417 U/l; median 305 U/l). Both the cavities and thin-walled cysts were demonstrated radiologically, but were more visible on CT than on the X-ray film. All patients responded well to the medication with cotrimoxazole, but the prognosis was poor with a survival time of only 0.3 to 16 months. CONCLUSION: PCP should be included in the differential diagnosis when HIV patients have cystic lung changes. Invasive diagnostic methods are often required to avoid wrong diagnosis and superfluous therapeutic interventions.

Adult↗

Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Study Group.

The molecular approach for the analysis of leukemia associated chromosomal translocations has led to the identification of prognostic relevant subgroups. In pediatric acute lymphoblastic leukemia (ALL), the most common translocations, t(9;22) and t(4;11), have been associated with a poorer clinical outcome. Recently the TEL gene at chromosome 12p13 and the AML1 gene at chromosome 21q22 were found to be involved in the translocation t(12;21)(p13;q22). By conventional cytogenetics, however, this chromosomal abnormality is barely detectable and occurs in less than 0.05% of childhood ALL. To investigate the frequency of the molecular equivalent of the t(12;21), the TEL/AML1 gene fusion, we have undertaken a prospective screening in the running German Berlin-Frankfurt-Münster (BFM) and Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) multicenter ALL therapy trials. We have analyzed 334 unselected cases of pediatric ALL patients consecutively referred over a period of 5 and 9 months, respectively. The overall incidence of the t(12;21) in pediatric ALL is 18.9%. The 63 cases positive for the TEL/AML1 chimeric products ranged in age between 1 and 12 years, and all but one showed CD10 and pre-B immunophenotype. Interestingly, one case displayed a pre-pre-B immunophenotype. Among the B-lineage subgroup, the t(12;21) occurs in 22.0% of the cases. Fifteen of 61 (24.6%) cases coexpressed at least two myeloid antigens (CD13, CD33, or CDw65) in more than 20% of the gated blast cells. DNA index was available for 59 of the 63 TEL/AML1 positive cases; a hyperdiploid DNA content (> or = 1.16) was detected in only four patients, being nonhyperdiploid in the remaining 55. Based on this prospective analysis, we retrospectively evaluated the impact of TEL/AML1 in prognosis by identifying the subset of B-lineage ALL children enrolled in the closed German ALL-BFM-90 and Italian ALL-AIEOP-91 protocols who had sufficient material for analysis. A total of 342 children were investigated for the presence of TEL/AML1 fusion gene and 99 cases (28.9%) were positive. The patients expressing the TEL/AML1 fusion mRNA appeared to have a better event-free survival (EFS) than the patients who lacked this chimeric product. Whereas three of the TEL/AML1 positive cases (3.0%) have relapsed to date, 27 patients without TEL/AML1 rearrangement (11.1%) suffered from relapse. To date, the only subset of B-lineage ALL with a favorable prognosis has been the hyperdiploid group (DNA index > or = 1.16 < 1.6). Our findings reinforce the need to include the molecular screening of the t(12;21) translocation within ongoing prospective ALL trials to prove definitively its prognostic impact.

Adolescent↗

Molecular biology in diagnosis and epidemiology of Helicobacter pylori: PCR for the detection and AP-PCR for characterization of patient isolates.

Infection with Helicobacter pylori causes chronic active gastritis and has been associated with gastric and duodenal ulcer disease. In biopsy samples of 110 patients with clinical symptoms of active gastritis, H. pylori was detected by means of the polymerase chain reaction (PCR), using species-specific primers defining a 858 bp DNA fragment of H. pylori urease beta-subunit. Sensitivity and specificity of the PCR was compared with culture, histology and Warthin-Starry stain (WSs), detection of H. pylori urease antibodies in serum and urease testing with the Campylobacter-like organism (CLO) test. PCR yielded specific amplification products in 53 cases, whereas culture of the organisms was positive in a subset of 50 cases. Only direct detection in histological sections of biopsy specimens had a higher sensitivity, with 65 positive samples. In contrast, the CLO test was negative in eleven culture-positive and PCR-positive cases. Significant urease antibody titres were found in 39 patients with histologically confirmed diagnosis. These results placed the sensitivity of PCR between tat of the Warthin-Starry stain (WSs) and that of culture. Therefore, PCR can be proposed as a useful rapid and time-saving technique for the detection of H.pylori in gastritis. For epidemiological purposes, fingerprinting with arbitrarily chosen primers by AP-PCR was evaluated. Strain-specific patterns with up to 13 fragments were achieved with 10-nucleotide or longer primers (21-nt) with a G + C content > or = 55%. Thirty-five of 40 strains investigated by this method were distinguishable with a single primer. These results suggest a high level of DNA sequence diversity within this species with the possibility of confirming the clonality in consecutive isolates from a single individual. Alternatively, an increased in-vivo mutation rate could be responsible for DNA divergence, resulting in specific strains for each individual patient.

Antibodies, Bacterial↗

Expression of intercellular adhesion molecule 1 (ICAM-1) in childhood acute lymphoblastic leukaemia: correlation with clinical features and outcome.

To investigate whether expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in childhood acute lymphoblastic leukaemia (ALL) has an impact on the biological behaviour of the disease, we evaluated 751 children of the ALL-BFM 90 trial with B-cell precursor- (n = 677) or T-cell-ALL (n = 74) for CD54 expression within immunological subgroups, its correlation to certain clinical features, and therapy outcome. The highest percentage of patients expressing CD54 was found in common- and pre-B-ALL (76.1% and 61.4%, respectively). There was intermediate expression in pre-pre-B-ALL (47.8%), and the lowest expression was detected in T-ALL (12.2%). A significant positive correlation could be demonstrated between low CD54 expression (< 20% stained blasts) and high peripheral leucocyte counts, central nervous system (CNS) involvement, and splenomegaly at the time of diagnosis (P < 0.01). In addition, CD54 expression was a favourable but not independent prognostic factor. Event-free survival estimate at 4.5 years was 86% for CD54+ patients (n = 463), compared with 78% for CD54- patients (n = 241) (P < 0.01). These findings demonstrate that CD54 expression has an impact on dissemination patterns and outcome of childhood ALL, and emphasizes the potential relevance of adhesion mechanisms in influencing clinical characteristics and prognosis of haematological malignancies.

Child↗

Invasive amoebiasis in two patients with AIDS and cytomegalovirus colitis.

Homosexual persons or human immunodeficiency virus (HIV)-infected patients frequently excrete cysts of nonpathogenic strains of Entamoeba histolytica ("Entamoeba dispar"). However, invasive amoebiasis is rare. We report two patients with AIDS and cytomegalovirus colitis in whom invasive amoebiasis was histologically diagnosed. It is concluded that E. histolytica has to be considered in HIV-infected patients with colitis.

AIDS-Related Opportunistic Infections↗

Role of cranial radiotherapy for childhood T-cell acute lymphoblastic leukemia with high WBC count and good response to prednisone. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster groups.

PURPOSE: The ALL-BFM 90 and AIEOP-ALL 91 studies share the same treatment backbone and have 5-year event-free survival (EFS) rates close to 75%. This study evaluated the impact of differing presymptomatic CNS therapies in T-cell acute lymphoblastic leukemia (T-ALL) patients with a good response to prednisone (PGR) according to WBC count and Berlin-Frankfurt-Münster (BFM) risk factor (RF). PATIENTS: A total of 192 patients (141 boys; median age, 7.5 years) with T-ALL, PGR, RF less than 1.7, and no CNS leukemia diagnosed between 1990 and 1995 were enrolled onto the ALL-BFM 90 (n = 123) or AIEOP-ALL 91 (n = 69) study. Presymptomatic CNS therapy consisted of cranial radiation (CRT) and intrathecal methotrexate (I.T. MTX) (11 doses) in the BFM study and of extended triple intrathecal therapy (T.I.T.) (17 doses) in the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study. Patients were divided into a low-WBC group (WBC count < 100,000/microL) and a high-WBC group (WBC count > 100,000/microL). EFS was compared using the log-rank test. RESULTS: For patients treated with CRT and I.T. MTX (BFM group), the 3-year EFS rate was 89.8% (SE = 3.5) for 99 patients in the low-WBC group versus 81.9% (SE = 8.2) in the high-WBC group (difference not significant). Conversely, for patients treated with T.I.T. alone (AIEOP group), the EFS rate was 80.6% (SE = 5.6) in 55 patients with a low WBC count versus 17.9% (SE = 11.0) in 14 patients with a high WBC count (P < .001). CONCLUSION: These data suggest that CRT may not be necessary in PGR T-ALL patients with a WBC count less than 100,000/microL; on the contrary, in patients with a high count, extended T.I.T. may be inferior to CRT and I.T. MTX.

Adolescent↗

A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia. Berlin-Frankfurt-Münster Study Group.

Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia (ALL) are good, with event-free survival (EFS) rates over 70%. However, for a subset of patients characterized by high-risk (HR) features the outcome is less favorable, with EFS rates below 50%. Intensification of chemotherapy may improve the outcome for those patients, but increased toxicity, particularly myelosuppression, limits the escalation of dose intensity. Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) is known to reduce myelosuppression after cancer chemotherapy in adults. The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy. Patients with HR pediatric ALL were randomized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Münster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously. In both groups, the planned interval between chemotherapy courses was a minimum of 21 days. We report here interim results of 34 patients. The incidence of febrile neutropenia (absolute neutrophil count <0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C) was 17% in children receiving r-metHuG-CSF, as compared with 40% in the control group (P = .007). In addition, the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient (P = .02). Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group (8% v 15%; P = .04), and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient (P = .02). A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF (P = .007). With a median follow-up of 3.3 years, the estimated EFS of 4 years is 41% +/- 12%. In conclusion, r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia, culture-confirmed infections, and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule.

Adolescent↗

Acute lymphoblastic leukemia of childhood: identification of two distinct regions of deletion on the short arm of chromosome 12 in the region of TEL and KIP1.

Cytogenetic analysis of acute lymphoblastic leukemia (ALL) of childhood identified nonrandom chromosomal abnormalities of the short arm of chromosome 12. The alterations include deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. To refine further the chromosomal localization of this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 100 primary ALL samples using 22 polymorphic markers and identified two distinct smallest common deleted regions on chromosome 12p13. One region is flanked by D12S77 and D12S98 and has a size of 4 cM. Twenty-six percent of informative patients showed LOH in this region. This region may contain the TEL gene. The other region is flanked by D12S269 and D12S308 including the KIP1 gene. Forty-four percent of informative patients showed LOH in this second region. Mutational analysis of KIP1 using polymerase chain reaction-single-strand conformation polymorphism analysis and Southern blot analysis showed no homozygous deletions and point mutations suggesting that the altered gene in this second region is not the KIP1. Clinical data showed that LOH of 12p was demonstrated more frequently in precursor-B ALLs (32 of 80; 40%) than in T-ALLs (1 of 20; 5%) (P = .0027). Furthermore, patients with 12p LOH were younger (P = .013), with a lower DNA index (P = .046), but they had the same survival rates at 3 years. In summary, these data suggest that two different tumor suppressor genes are on chromosome arm 12p, which act separately in the development of childhood precursor-B ALLs. One of the tumor suppressor genes is in the region the KIP1 gene, but our data suggest this gene is not abnormal. The other target is in the region of the TEL gene; and this candidate deserves further study.

Cell Cycle Proteins↗

CMV-antigenemia in peripheral blood for the diagnosis of CMV disease in HIV-infected patients.

In a prospective study of HIV patients with suspected cytomegalovirus (CMV) disease (n = 144; 140 men, four women; aged 23-69 years, median 38 years; CD4 cells 0-400, median 20/microliters), 242 blood samples were examined for the presence of CMV-pp65 antigen in peripheral blood polymorphonuclear leucocytes by use of monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase staining. All patients were thoroughly examined for existing CMV disease at first visit and during follow-up (at least 2 months or until death: 0-24 months, median 14 months). In 43/486 samples of patients with CMV disease, the antigen-test was positive and in 179/194 samples of patients without CMV disease the test was negative, resulting in a sensitivity of 90% and a specificity of 93% for the presence of CMV disease in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Resting energy expenditure, weight loss, and altered body composition in HIV infection.

Failure to downregulate resting energy expenditure (REE) as an adaption to anorexia or malabsorption is often stated as the major cause of weight loss in individuals with AIDS. In a prospective study, REE was compared with weight changes in HIV-infected patients. The impact of altered body composition on REE was reassessed by critical review of the literature. Patients were 65 male HIV-infected patients, 28 with recent weight loss (WL), and 37 who were weight stable (WS); 50/65 patients had AIDS, and 29/65 had acute infections; 29 male healthy persons served as controls. Indirect calorimetry, prospective intake protocol, and bioelectrical impedance analysis were performed. Absolute REE was lower in WL patients than in controls (1459 +/- 309 versus 1711 +/- 151 kcal/d, p < 0.001) and in WS patients (1625 +/- 402 kcal/d, p < 0.05). REE/kg body cell mass (BCM) was higher in WL and WS than in controls (both p < 0.01) due to lower BCM in both patient groups (p < 0.001). REE (%Harris-Benedict) was not different among the three groups. Weight changes around the measurement were not correlated to REE (r2 = 0.0008, p = 0.82). REE was independent of diarrhea, acute infection, fever, or caloric intake. REE had a stronger correlation to body weight and to Harris-Benedict's prediction than to fat-free mass or BCM. REE explains < 1% of weight changes. Many patients can downregulate REE as an adaption to anorexia and/or malabsorption. Higher REE/kg BCM does not signify hypermetabolism at the cellular level but can be explained by the maintenance of energy-consuming visceral tissue within the BCM during BCM loss.

Acquired Immunodeficiency Syndrome↗

Evidence for genetic regulation of susceptibility to toxoplasmic encephalitis in AIDS patients.

The frequency of HLA-DQ antigens in AIDS patients with toxoplasmic encephalitis (TE) were examined. HLA-DQ3 was significantly more frequent in white North American AIDS patients with TE (85.0%) than in the general white population (51.8%; P = .007, corrected P = .028) or randomly selected control AIDS patients who had not developed TE (40.0%; P = .016). In contrast, the frequency of HLA-DQ1 was lower in TE patients than in healthy controls (40.0% vs. 66.5%, P = .027), but this difference did not reach statistical significance when corrected for the number of variables tested (corrected P = .108 for the general white population). HLA-DQ3 thus appears to be a genetic marker of susceptibility to development of TE in AIDS patients, and DQ1 may be a resistance marker. These HLA associations with disease indicate that development of TE in AIDS patients is affected by a gene or genes in the HLA complex and that HLA-DQ typing may help in decisions regarding TE prophylaxis.

AIDS-Related Opportunistic Infections↗