Detection of Histoplasma capsulatum Antigen in Panamanian Patients with Disseminated Histoplasmosis and AIDS

Abstract

Histoplasmosis is a common endemic mycosis in the Americas, often causing severe disease in patients with AIDS. Antigen detection has become an important method for rapid diagnosis of histoplasmosis in the United States but not in Central or South America. Isolates from patients in the United States are predominantly found to be class 2 isolates when typed using the nuclear gene YPS3, while isolates from Latin America are predominantly typed as class 5 or class 6. Whether infection with these Latin American genotypes produces positive results in the Histoplasma antigen assay has not been reported. In this study, we have compared the sensitivity of antigen detection for AIDS patients from Panama who had progressive disseminated histoplasmosis to that for those in the United States. Antigenuria was detected in the MVista Histoplasma antigen enzyme immunoassay (EIA) in 95.2% of Panamanian cases versus 100% of U.S. cases. Antigenemia was detected in 94.7% of the Panamanian cases versus 92% of the U.S. cases. Two clinical isolates from Panama were typed using YPS3 and were found to be restriction fragment length polymorphism class 6. We conclude that the MVista Histoplasma antigen EIA is a sensitive method for diagnosis of histoplasmosis in Panama.Progressive disseminated histoplasmosis (PDH) is a common and serious opportunistic disease among patients with AIDS in the United States and Latin America. In Panama, PDH occurred in 8% of hospitalized patients from 1997 to 2003 and was fatal in 12% of cases (6). The clinical picture was similar to that reported elsewhere and usually included fever, weight loss, and respiratory symptoms, often in association with diarrhea, as well as hepatosplenomegaly, hepatic enzyme elevation, and pancytopenia. Skin lesions were noted in 17% of the Panamanian cases (6), lower than the observed rate for cases from Brazil (66%) but higher than that for cases from the United States (ϳ3%) (7).Disease in patients in Mexico and Latin America has been described as being caused by isolates of Histoplasma capsulatum var. capsulatum that exhibit distinct genetic profiles in comparison to those from the United States (3, 8, 9). Keath et al. (9) first described typing based upon restriction fragment length polymorphism (RFLP) in the YPS3 gene. They showed that Panamanian strains were typed as YPS3 class 3, 5, or 6, while the North American strains were predominantly class 2. Later, Kasuga et al. used the DNA sequence substitution rates in four independent protein-coding genes to identify at least eight different genotypes, or clades (8). North American class 2 was the predominant genotype in the United States and Latin American group A in Latin America. Latin American group B was found only in Columbia and Argentina. Based on only four isolates from Panama included in the study by Kasuga et al.,Panamanian strains included Latin American group A and a lone lineage, designated H81.The diagnosis of PDH relies on demonstration of the organism in clinical specimens or detection of antigen in body fluids ...

Investigation of the Efficacy of Micafungin in the Treatment of Histoplasmosis Using Two North American Strains of Histoplasma capsulatum

“…The H. capsulatum isolates were IU-CT (3, 11) and 94-255 (8). Genotyping using YPS3 (1,9) showed that the 94-255 isolate did not express YPS3 and, thus, was a class 1 strain, whereas the IU-CT isolate expressed YPS3, which is characteristic for class 2 (Fig. 1A), the predominant type in North America (20).…”

Antigen detection for diagnosis of the endemic mycoses

“…In AIDS patients with histoplasmosis, antigenemia was present in 95% in the MVista EIA compared with 87% in the original EIA. Recently, these fi ndings have been extended to Panamanian patients with AIDS complicated by PDH [21]. Antigenuria and antigenemia were detected in 95% of the Panamanian cases compared with 100% and 92%, respectively, of the US cases.…”

Improved Detection of Histoplasma Antigenemia following Dissociation of Immune Complexes

“…For example, in the quantitative MVista Histoplasma antigen enzyme immunoassay (EIA), among patients with AIDS and progressive disseminated histoplasmosis (PDH), antigenuria was detected in 95 to 100% compared to 92 to 95% for antigenemia (1,3). Previously, we noted improvement in the sensitivity for detection of antigenuria after ultrafiltration (2).…”

“…Second, urine may not be available in patients with renal failure. Third, antigenuria levels early in the infection often are above the reportable range of the MVista Histoplasma antigen EIA (1,3). Clearance of antigenemia may provide a better marker for response to therapy in such cases.…”