Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico
Por:
Martinez-Gamboa, Areli, Niembro-Ortega M.D., Torres-Gonzalez, Pedro, Santiago-Cruz, Janeth, Velázquez-Zavala N.G., Rangel-Cordero, Andrea, Crabtree-Ramirez, Brenda, Gamboa-Dominguez, Armando, Reyes-Gutierrez, Edgardo, Reyes-Teran, Gustavo, Lozano-Fernandez V.H., Ahumada-Topete V.H., Martinez-Ayala, Pedro, Manriquez-Reyes, Marisol, Ramírez-Hinojosa J.P., Rodriguez-Zulueta, Patricia, Hernandez-Leon, Christian, Ruiz-Quinones, Jesus, Rivera-Martínez N.E., Chaparro-Sanchez, Alberto, Andrade-Villanueva, Jaime, González-Hernández L.A., Cruz-Martinez, Sofia, Flores-Barrientos, Oscar, Gaytán-Martínez J.E., Magaña-Aquino M., Cervantes-Sanchez, Axel, Olivas-Martinez, Antonio, Araujo-Melendez, Javier, Del Rocio Reyes-Montes, Maria, Duarte-Escalante, Esperanza, Frías-De León M.G., Ramírez J.A., Taylor M.L., de León-Garduño A.P., Sifuentes-Osornio, Jose
Publicada:
1 mar 2021
Resumen:
Author summary
Histoplasmosis, an infection caused by Histoplasma capsulatum, is
prevalent in the Americas, it is a common cause of pulmonary acute
disease in cave explorers, speleologists, boy scouts and some other
people in circumstantial risk, in most of these people the infection is
commonly self-limited. However, in people living with HIV (PLWHIV) this
infection might be acquired without specific exposition and it behaves
like a severe disease with high fever, consumption, septic shock and
death. Thus, there is a need for rapid and accurate methods for
diagnosis in this population at risk. We tested five different methods
for rapid diagnosis (three based on antigen detection in urine and two
molecular assays based on PCR amplification, widely used) of
disseminated histoplasmosis and we were able to demonstrate that two
urine antigen detection tests (clarus Histoplasma GM Enzyme Immunoassay
kit and MiraVista Histoplasma Urine Antigen LFA) showed excellent
performance to diagnose of disseminated histoplasmosis in PLWHIV. The
antigen detection tests have advantages over the PCR tests, their
performance is higher, they are commercial standardized tests, easy to
perform, and provide results in hours, therefore the integration of
these tests in clinical laboratories will certainly impact on early
diagnosis/treatment and consequently on the outcome of patients.
Background
The progressive disseminated histoplasmosis (PDH) has been associated
with severe disease and high risk of death among people living with HIV
(PLWHIV). Therefore, the purpose of this multicenter, prospective,
double-blinded study done in ten Mexican hospitals was to determine the
diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine
using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM
Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen
LFA (MVHUALFA); as well as the Hcp100 and 1281-1283(220)SCAR nested PCRs
in blood, bone-marrow, tissue biopsies and urine.
Methodology/Principal findings
We included 415 PLWHIV older than 18 years of age with suspicion of PDH.
Using as diagnostic standard recovery of H. capsulatum in blood, bone
marrow or tissue cultures, or histopathological exam compatible,
detected 108 patients (26%, [95%CI, 21.78-30.22]) with proven-PDH.
We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the
sensitivity/specificity values obtained were 67.3% (95% CI, 57.4-76.2)
/ 96.2% (95% CI, 93.2-98.0) for IAHE, 91.3% (95% CI, 84.2-96.0) /
90.9% (95% CI, 87.0-94.0) for cHGEI IMMY and 90.4% (95% CI,
83.0-95.3) / 92.3% (95% CI, 88.6-95.1) for MVHUALFA.
The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone
marrow, tissue and urine samples respectively; the
sensitivity/specificity values obtained were 62.9% (95%CI, 53.3-72.5)/
89.5% (95%CI, 86.0-93.0), 65.9% (95%CI, 56.0-75.8)/ 89.0% (95%CI,
85.2-92.9), 62.1% (95%CI, 44.4-79.7)/ 82.6% (95%CI, 71.7-93.6) and
34.9% (95%CI, 24.8-46.2)/ 67.3% (95%CI, 60.6-73.5) respectively; and
1281-1283(220)SCAR nested PCR was performed on 392, 344, 75 and 291,
respectively; the sensitivity/specificity values obtained were 65.3%
(95% CI, 55.9-74.7)/ 58.8% (95%CI, 53.2-64.5), 70.8% (95%CI,
61.3-80.2)/ 52.9% (95%CI, 46.8-59.1), 71.4% (95%CI, 54.7-88.2)/
40.4% (95%CI, 26.4-54.5) and 18.1% (95%CI, 10.5-28.1)/ 90.4%
(95%CI, 85.5-94.0), respectively.
Conclusions/Significance
The cHGEI IMMY and MVHUALFA tests showed excellent performance for the
diagnosis of PDH in PLWHIV. The integration of these tests in clinical
laboratories will certainly impact on early diagnosis and treatment.
Filiaciones:
Martinez-Gamboa, Areli:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Niembro-Ortega M.D.:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Torres-Gonzalez, Pedro:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Santiago-Cruz, Janeth:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Velázquez-Zavala N.G.:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Rangel-Cordero, Andrea:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Crabtree-Ramirez, Brenda:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Gamboa-Dominguez, Armando:
Tlalpan, Mexico City, Mexico
Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
Reyes-Gutierrez, Edgardo:
Tlalpan, Mexico City, Mexico
Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
Reyes-Teran, Gustavo:
Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
Lozano-Fernandez V.H.:
Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
Ahumada-Topete V.H.:
Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
Martinez-Ayala, Pedro:
HIV Unit, Hospital Civil de Guadalajara "Fray Antonio Alcalde"
Manriquez-Reyes, Marisol:
Department of Internal Medicine, Hospital de Alta Especialidad de Veracruz
Ramírez-Hinojosa J.P.:
Department of Infectious Diseases, Hospital General Dr. Manuel Gea González
Rodriguez-Zulueta, Patricia:
Department of Infectious Diseases, Hospital General Dr. Manuel Gea González
Hernandez-Leon, Christian:
Area of Infectious Diseases, Department of Internal Medicine, Hospital General de Puebla "Dr. Eduardo Vázquez Navarro"
Ruiz-Quinones, Jesus:
Intensive Care Unit, Department of Internal Medicine, Hospital "Dr. Juan Graham Casasus"
Rivera-Martínez N.E.:
Adult Infectious Diseases Department, Hospital Regional de Alta Especialidad de Oaxaca, HRAEO
Chaparro-Sanchez, Alberto:
Department of Infectious Diseases, Hospital de Infectología del Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social
Andrade-Villanueva, Jaime:
HIV Unit, Hospital Civil de Guadalajara "Fray Antonio Alcalde"
González-Hernández L.A.:
HIV Unit, Hospital Civil de Guadalajara "Fray Antonio Alcalde"
Cruz-Martinez, Sofia:
Adult Infectious Diseases Department, Hospital Regional de Alta Especialidad de Oaxaca, HRAEO
Flores-Barrientos, Oscar:
Intensive Care Unit, Department of Internal Medicine, Hospital "Dr. Juan Graham Casasus"
Gaytán-Martínez J.E.:
Department of Infectious Diseases, Hospital de Infectología del Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social
Magaña-Aquino M.:
Department of Internal Medicine, Hospital Central Dr. Ignacio Morones Prieto
Cervantes-Sanchez, Axel:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Olivas-Martinez, Antonio:
Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Araujo-Melendez, Javier:
Department of Internal Medicine, Hospital Central Dr. Ignacio Morones Prieto
Del Rocio Reyes-Montes, Maria:
Mycology Unit, Department of Microbiology and Parasitology, Facultad de Medicina, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
Duarte-Escalante, Esperanza:
Mycology Unit, Department of Microbiology and Parasitology, Facultad de Medicina, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
Frías-De León M.G.:
Research unit, Hospital Regional de Alta Especialidad de Ixtapaluca, Mexico State, Mexico
Ramírez J.A.:
Mycology Unit, Department of Microbiology and Parasitology, Facultad de Medicina, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
Taylor M.L.:
Mycology Unit, Department of Microbiology and Parasitology, Facultad de Medicina, Universidad Nacional Autónoma de MéxicoMexico City, Mexico
de León-Garduño A.P.:
Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Sifuentes-Osornio, Jose:
Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
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