Ram P. Tewari

Diagnosis of Disseminated Histoplasmosis by Detection of Histoplasma capsulatum Antigen in Serum and Urine Specimens

The diagnosis of Histoplasma capsulatum infection by serologic testing for the presence of antibodies is limited by a high rate of false positive and false negative results and by the requirement that the patient have a normal immune response. We have developed a radioimmunoassay for the detection of H. capsulatum antigen in urine and serum specimens. Antigenuria was noted in 20 of 22 episodes of disseminated histoplasmosis that occurred in 16 patients, in 6 of 32 patients with self-limited infection, in 2 of 32 patients with cavitary histoplasmosis, and in 4 of 8 patients with a sarcoid-like illness caused by H. capsulatum. The detection of antigen in urine was reproducible in 38 of 41 (93 percent) retests of specimens. H. capsulatum antigen was also detected in the serum during 11 of the 22 episodes of disseminated histoplasmosis, in none of the 12 episodes of other types of histoplasmosis in patients with antigenuria, in 1 of the 33 patients with histoplasmosis who lacked the urinary antigen, and in none of the 50 controls. Antigenemia and antigenuria decreased after initiation of antifungal therapy and recurred in patients who had a relapse. We conclude that this radioimmunoassay for H. capsulatum antigen represents a useful new method for the rapid diagnosis of disseminated histoplasmosis.

Pathogenic Differences between North American and Latin American Strains of Histoplasma capsulatum var. capsulatum in Experimentally Infected Mice

ABSTRACT Clinical differences in histoplasmosis between North America and Brazil prompted investigation of experimental infection with representative strains. Mortality was higher with Latin American strains, and lung pathology showed large necrotizing granuloma with prominent neutrophilic infiltration. Chronic disease was unique to the North American strain.

Characterization of Lymphocytes Responsible for Protective Immunity to Histoplasmosis in Mice/Charakterisierung von Lymphozyten der protektiven Immunität gegen Histoplasmose bei Mäusen*

Summary: Purified thymus‐derived (T) and bone marrow derived (B) lymphocytes were obtained from spleens of C3H/HeN mice immunized with live yeast cells of H. capsulatum. Unfractionated spleen lymphocytes contained 44–46% T cells and 40–43% B cells. Adoptive transfer of unfractionated lymphocytes and T‐enriched lymphocytes conferred significant protection against a lethal challenge with yeast cells of H. capsulatum (p < 0.001) whereas, only a minimal level of protection was observed in mice receiving B‐cell enriched subpopulations. The unfractionated lymphocytes and T and B cells retained their in vitro immunological characteristics in lymphocyte transformation assays. Significant migration inhibition of PEC from recipients of unfractionated and T cells was observed in the presence of Histoplasma antigens (p < 0.01); the inhibition was similar to that seen with PEC from immunized donors. In contrast, the PEC from recipients of B cells did not show inhibition of macrophage migration under similar conditions. These results indicate that the purified lymphocytes retained their immunological characteristic and that the significant protective immunity is conferred only by T cells.

Hormonal modulation of the vaginal bacterial flora in experimental polycystic ovarian disease.

Rats exposed to constant light develop polycystic ovarian (PCO) disease with persistent estrus, representing an estrogen‐dominant condition. Herein, we report that fluctuations seen in the vaginal microflora in cyclic rats were not observed in PCO rats with persistent estrus. The vaginal‐cervical mucosa of PCO rats showed numerous adherent bacteria by scanning electron microscopy, similar to that seen in proestrus and estrus rats, but unlike the diestrus rats in which fewer organisms adhered to the mucosa. Administration of human chorionic gonadotropin induced ovulation in PCO rats, which was associated with a significant decrease in serum estradiol, an increase in progesterone, and a significant decrease in the estradiol/progesterone ratio compared with baseline values (P < 0.01). This also resulted in an influx of leukocytes in the vagina with a significant decrease in vaginal anaerobic as well as aerobic bacterial flora. These data demonstrate that loss of cyclic ovarian activity in PCO rats with persistent estrus causes increased bacterial colonization of the vaginal‐cervical mucosa, and the ovarian hormones appear to modulate the colonization of bacteria in the lower genital tract.