Clinical prediction model for differentiation of disseminated Histoplasma capsulatum and Mycobacterium avium complex infections in febrile patients with AIDS.

BACKGROUND: Disseminated infection with Histoplasma capsulatum and Mycobacterium avium complex (MAC) in patients with AIDS are frequently difficult to distinguish clinically. METHODS: We retrospectively compared demographic information, other opportunistic infections, medications, symptoms, physical examination findings and laboratory parameters at the time of hospital presentation for 32 patients with culture documented disseminated histoplasmosis and 58 patients with disseminated MAC infection. RESULTS: Positive predictors of histoplasma infection by univariate analysis included lactate dehydrogenase level, white blood cell (WBC) count, platelet count, alkaline phosphatase level, and CD4 cell count. By multivariate logistic regression analysis, those characteristics that remained significant included a lactate dehydrogenase value > or =500 U/L (risk ratio [RR], 42; 95% confidence interval [CI], 18.53-97.5; p < .001), alkaline phosphatase < or =300 U/L (RR, 9.35; 95% CI, 2.61-33.48; p = .008), WBC < or =4.5 x 10(6)/L (RR, 21.29; 95% CI, 6.79-66.75; p = .008), and CD4 cell count (RR, 0.958; 95% CI, 0.946-0.971; p = .001). CONCLUSIONS: A predictive model for distinguishing disseminated histoplasmosis from MAC infection was developed using lactate dehydrogenase and alkaline phosphatase levels as well as WBC count. This model had a sensitivity of 83%, a specificity of 91%, and a misclassification rate of 13%.

Acute respiratory failure associated with cryptococcosis in patients with AIDS: analysis of predictive factors.

The incidence of acute respiratory failure (ARF) associated with cryptococcal disease in patients with AIDS is underestimated in the literature. We performed a retrospective, case-control (referent) study to determine the prevalence of ARF associated with cryptococcal disease and analyzed associated factors. Potential cases of ARF were identified at four university-affiliated teaching hospitals from a cohort of 210 patients with AIDS who had positive cryptococcal antigen tests and/or Cryptococcus neoformans isolated from any body site. Twenty-nine of the 210 (13.8%) had ARF associated with cryptococcal disease. Nineteen were thought to have respiratory failure due solely to C. neoformans. The demographic, clinical, laboratory, treatment, and outcome data of 19 cases of respiratory failure were compared with data for 20 patients without respiratory failure. In-hospital mortality was 100% and median survival was 2 days for cases, vs. 25% and > 365 days, respectively, for referents. The clinical presentation was identical to that of Pneumocystis carinii pneumonia. In multivariate analysis, variables independently predictive of ARF in patients with cryptococcal disease were black race, a lactate dehydrogenase level of > or = 500 IU/L, the presence of interstitial infiltrates, and the presence of cutaneous lesions. ARF with cryptococcosis in patients with AIDS is associated with disseminated disease and high mortality. The diagnosis frequently is not considered before death. Serum cryptococcal antigen testing is a sensitive and rapid screening method.

Colonization by Streptococcus pneumoniae among human immunodeficiency virus-infected adults: prevalence of antibiotic resistance, impact of immunization, and characterization by polymerase chain reaction with BOX primers of isolates from persistent S. pneumoniae carriers.

Pharyngeal colonization by Streptococcus pneumoniae was evaluated in 103 human immunodeficiency virus (HIV)-infected subjects (<200 CD4 cells/microL, 57; > or = 200 CD4 cells/microL, 46) and 39 non-HIV-infected controls who were participants in a vaccine study. At baseline, 7%, 20%, and 10% of subjects in the <200 and > or = 200 CD4 cell groups and in the control group were colonized with S. pneumoniae: Rates at 6 months were 23%, 22%, and 0%, respectively. Of 34 isolates from HIV-infected subjects, 25 were penicillin-resistant and 19 were resistant to > or = 3 antimicrobials; of 8 isolates from controls, 1 was resistant. Resistance to trimethoprim-sulfamethoxazole was significantly higher among HIV-infected subjects with <200 CD4 cells/microL than in those with more CD4 cells. Polymerase chain reaction DNA analysis with BOX primers demonstrated that 12 HIV-infected subjects were persistently colonized with the same S. pneumoniae strain for > or = 1 month compared with none of the controls. HIV-infected subjects were more likely to be persistent pneumococcal carriers and to carry antibiotic-resistant isolates than were non-HIV-infected subjects.

IgG antibody to pneumococcal capsular polysaccharide in human immunodeficiency virus-infected subjects: persistence of antibody in responders, revaccination in nonresponders, and relationship of immunoglobulin allotype to response.

Human immunodeficiency virus (HIV)-infected persons are less likely than are noninfected persons to respond to vaccination with pneumococcal polysaccharides (PPS). Among those who respond, however, similar IgG levels may be achieved. HIV-infected men immunized with pneumococcal vaccine were classified as high- or low-level responders (IgG > or = 1 microgram/mL for > or = 3 of 5 PPS [high] or for < or = 1 PPS [low]). One and 2 years after immunization, geometric mean IgG levels and the percentages of subjects with IgG levels > or = 1 microgram/mL were similar for HIV-infected and for healthy high-level responders (controls) for all PPS except for serotype 8. Among HIV-infected low-level responders, revaccination with a double dose of pneumococcal vaccine did not stimulate IgG responses. Responsiveness of HIV-infected white patients was significantly associated with the Km(1)- negative allotype. These findings support current general recommended guidelines for administering pneumococcal vaccine to HIV-infected persons. Nonresponders will not benefit from revaccination.

Case report: vitamin D-mediated hypercalcemia in fungal infections.

Hypercalcemia has been well described in a variety of neoplastic and granulomatous diseases. One mechanism for this hypercalcemia is via the excess production of 1,25-dihydroxyvitamin D from extra-renal sources. The authors describe an AIDS patient infected with Cryptococcus neoformans who had suggestive evidence of vitamin D-mediated hypercalcemia. He had an elevated serum 1,25-dihydroxyvitamin D value, a normal 25-hydroxyvitamin D value, and low values for parathyroid hormone and parathyroid hormone-related peptide. Most previously reported cases of hypercalcemia associated with fungal infections did not include sufficient evidence to implicate a role for excess 1,25-dihydroxyvitamin D production, except for two case reports involving patients with hypercalcemia with infections due to Pneumocystis carinii and Candida albicans. The authors' patient's hypercalcemia resolved during treatment of his underlying infection. Patients with hypercalcemia or in whom hypercalcemia develops during a disseminated fungal infection should have vitamin D metabolites measured as part of their work-up.

Phenotypic and functional changes in peripheral blood monocytes during progression of human immunodeficiency virus infection. Effects of soluble immune complexes, cytokines, subcellular particulates from apoptotic cells, and HIV-1-encoded proteins on monocytes phagocytic function, oxidative burst, transendothelial migration, and cell surface phenotype.

We postulated that changes in the cell surface display of molecules that facilitate cell-cell and cell-matrix adhesions may reflect the changing immunosurveillance capacity of blood monocytes during progression of human immunodeficiency virus (HIV) infections. In Centers for Disease Control (CDC) stage A patients, whose monocytes' ability to phagocytose bacteria and generate reactive oxygen intermediates is often increased, the frequency of monocytes expressing CD49d, HLA-DP, HLA-DQ, and an activation epitope of CD11a/CD18 was increased and monocyte transendothelial migration was unimpaired. In CDC stage B/C patients, whose monocytes' ability to phagocytose bacteria and migrate across confluent endothelial monolayers was diminished, surface expression of CD49e and CD62L and the percentage of monocytes expressing CD18, CD11a, CD29, CD49e, CD54, CD58, CD31, and HLA-I were significantly decreased. Incubating normal donor monocytes with immune complexes in vitro reproduced the phenotypic and functional abnormalities seen in stage B/C patients. By contrast, in vitro stimulation with subcellular particulates released by apoptotic lymphocytes reproduced changes seen in stage A patients' monocytes. Although circulating monocytes appear to be activated at all stages, these data suggest that the high levels of circulating immune complexes, found predominantly in the later stages of HIV infection, may be particularly instrumental in reducing the monocyte's capacity to maintain surveillance against infection.

Failure of providers to vaccinate HIV-infected men against hepatitis B: a missed opportunity.

OBJECTIVE: To carry out an audit of hepatitis B immunization practices in an outpatient HIV clinic. METHODS: We reviewed the medical records of all new HIV-infected patients seen between October 1, 1990 and December 31, 1991. RESULTS: The 125 patients were men with a mean age and CD4 count of 43 yr and 240 cells/mm3, respectively. Fourteen percent (14%) of men who showed a clear need for vaccine, having no HBV markers, were not vaccinated by the clinic staff. Further, 16% whose susceptibility to HBV infection was unclear, with anti-HBc as a sole HBV marker, were not evaluated with a booster dose of hepatitis B vaccine in an attempt to elicit an anamnestic response. CONCLUSIONS: In failing to vaccinate or evaluate the 30% of patients without HBsAg or anti-HBs, our providers are missing an important opportunity in preventive medicine. We urge others to examine their own hepatitis B screening and vaccination practices.

Effect of HIV transmission category and CD4 count on the occurrence of diarrhea in HIV-infected patients.

This study was designed to assess the relative contributions of HIV transmission category and immunodeficiency to the risk of HIV-related diarrhea. We reviewed the medical records of 169 HIV-infected non-AIDS patients seen between 1986 and 1990 at the Houston VA Special Medicine Clinic. The prevalence of diarrhea at any given clinic visit ranged from 3% to 7%. Diarrhea was three times more common in homosexual/bisexual men [odds ratio = 3.0 (1.01-9.53)], and this pattern persisted when stratified by CD4 count. Previous studies have focused mainly on the detection of enteric organisms in patients with HIV-related diarrhea. Studies of the temporal relationships between sexual practices, enteric pathogens, diarrhea, and immunodeficiency are needed to clarify the pathogenesis of HIV-related diarrhea.

A simple clinical staging system that predicts progression to AIDS using CD4 count, oral thrush, and night sweats.

OBJECTIVE: To develop a simple clinical staging system based on CD4 count and clinical variables that predicts progression to AIDS in HIV-infected non-AIDS patients. DESIGN: Retrospective cohort study. SETTING: A primary care outpatient clinic for HIV-infected patients at a VA Medical Center. PATIENTS: One hundred seventy-six HIV-infected non-AIDS patients seen at the Houston VA Special Medicine Clinic between January 1986 and December 1990 and followed for a mean of 22 months. Fifty-four patients (31%) progressed to AIDS during follow-up. MEASUREMENTS: The medical records were reviewed, and data corresponding to the initial (baseline) clinic visit and subsequent six-month visits were extracted. MAIN RESULTS: "Predictive" baseline variables (i.e., those associated with progression to AIDS) were first identified and then examined in Cox proportional hazards modeling. In the final model, CD4 category, oral thrush, and night sweats made significant independent contributions. A three-stage prognostic system was constructed by assigning points to the three variables: CD4 > 500 cells/mm3 = 0; 500 > or = CD4 > or = 200 = 1; CD4 < 200 = 2; presence of oral thrush = 1; presence of night sweats = 1. Stages were assigned as follows: stage I = 0 points, stage II = 1-2 points, and stage III = 3-4 points. The proportions of patients who progressed to AIDS were: stage I, 6/39 (15%); stage II, 31/106 (29%); and stage III, 17/31 (55%). CONCLUSIONS: These results demonstrate that simple, clinically sensible prognostic staging systems that predict progression to AIDS can be constructed using CD4 count and clinical variables.