Chapter 6. Outstanding Questions in the Field from the Curious Coccidioidomycosis


Raimunda Sâmia Nogueira Brilhante1, Marcos Fábio Gadelha Rocha1,2, José Júlio Costa Sidrim1
and Germana Costa Paixão1
1Department of Pathology and Legal Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
2College of Veterinary, State University of Ceará, Fortaleza, Ceará, Brazil

Part of the book: The Book of Fungal Pathogens


Coccidioidomycosis is a fungal infection of the Western Hemisphere that is endemic in regions having low rainfall and soils with high salt content. Coccidioidomycosis was first described in 1892 by Alejandro Posadas in Argentina. The genus is dimorphic in nature, and in its asexual form it exists as a mycelium and spherules. Currently there are two species in the genus, called Coccidioides immitis and Coccidioides posadasii. The first one has been isolated in California while the second once has been found in other regions of the USA, as well as in some places in Central and South America. The two species can be distinguished by molecular techniques, but they are not routinely identified by species in the laboratory. The two species are indistinguishable by clinical manifestations and in vitro sensitivity tests. Most patients have self-limited or even asymptomatic infection/disease. Among those with symptomatic illness, 90% experience respiratory symptoms, with only 1% to 10% progressing to severe or disseminated illness. In most regions, the clinical diagnosis of coccidioidomycosis is based on direct examination of sputum and histopathological results of biopsies or autopsies. Coccidioidomycosis is definitively diagnosed when spherules are observed through pathological examination or fungal structures are observed in cultures. The use of serology requires an understanding of the tests involved, and the results must be interpreted in the context of time and ability to develop a host immune response. Azoles, especially fluconazole, are the mainstay of therapy. The need to treat mild lung disease is controversial, but treatment is mandatory in cases of severe or prolonged disease, dissemination, or severe immunosuppression. Severe infections may require amphotericin B. In this context, Coccidioidomycosis is best managed by a multidisciplinary team, where patients are monitored regularly.

Keywords: Coccidioides, coccidioidomycosis, etiology, pathophysiology, diagnosis, treatment


Adams, M., Lainhart, W. A Review of Diagnostics for Coccidiomycosis. Clin. Microbiol. Newsl., 2021 43,
Akram, S. M., Koirala J. Coccidioidomycosis. StatPearls: Treasure Island (FL), 2022.
Barker, B. M., Litvintseva, A. P., Riquelme, M., Vargas-Gastélum, L. Coccidioides Ecology and Genomics.
Med. Mycol., 2019 57, S21-S29.
Bialek, R., Kern, J., Herrmann, T., Tijerina, R., Ceceñas, L., Reischl, U., González, G. M. PCR Assays for
Identification of Coccidioides posadasii Based on the Nucleotide Sequence of the Antigen 2/Proline-Rich
Antigen. J. Clin. Microbiol., 2004 42, 778-783.
Binnicker, M. J., Buckwalter, S. P., Eisberner, J. J., Stewart, R. A., McCullough, A. E., Wohlfiel, S. L.,
Wengenack, N. L. Detection of Coccidioides Species in Clinical Specimens by Real-Time PCR. J. Clin.
Microbiol., 2007 45, 173-178.
Bowers, J. R., Parise, K. L., Kelley, E. J., Lemmer, D., Schupp, J. M., Driebe, E. M., Engelthaler, D. M., Keim,
P., Barker, B. M. Direct Detection of Coccidioides from Arizona Soils Using Coccienv, a Highly Sensitive
and Specific Real-Time PCR Assay. Med. Mycol., 2019 57, 246-255.
Crum, N. F. Coccidioidomycosis: A Contemporary Review. Infect. Dis. Ther., 2022 4, 1-30.
Del Rocío, R. M. M., Pérez-Huitrón, M. A., Ocaña-Monroy, J., Frías-De-León, M. G., Martínez-Herrera, E.,
Arenas, R., Duarte-Escalante, E. The Habitat of Coccidioides spp. and the Role of Animals as Reservoirs
in Disseminators to Nature. BMC. Infect. Dis., 2016 16, 550-558.
Deresinski, S., Mirels, L. F. Coccidioidomycosis: What a Long, Strange Trip It’s Been.
Med. Mycol., 2019 57, S3-S15.
Egeberg, R. O., Elconin, A. E., Egeberg, M. C. Effect of Salinity and Temperature on Coccidioides immitis
and Three Antagonistic Soil Saprophytes. J. Bacteriol., 1964 88, 473-476.
Farness, O. J. Coccidioidal Infection in a Dog. J. Am. Vet. Med. Assoc., 1940 97, 263-264.
Fisher, M. C., Koenig, G. L., White, T. J., Taylor, J. W. Molecular and Phenotypic Description of Coccidioides
posadasii sp. nov., Previously Recognized as the Non-California Population of Coccidioides immitis.
Mycologia, 2002 94, 73-84.
Fu, L., Wang, B., Yuan, T., Chen, X., Ao, Y., Fitzpatrick, T., Li, P., Zhou, Y., Lin, Y., Duan, Q., Luo, G., Fan,
S., Lu, Y., Feng, A., Zhan, Y., Liang, B., Cai, W., Zhang, L., Du, X., Li, L., Shu, Y., Zou, H. Clinical
Characteristics of Coronavirus Disease 2019 (COVID-19) in China: a Systematic
Review and Meta Analysis. J. Infect., 2020 80, 656-665.
Gabe, L. M., Malo, J., Knox, K. S. Diagnosis and Management of Coccidioidomycosis. Clin. Chest. Med.,
2017 38, 417-433.
Galgiani, J. N., Ampel, N. M., Blair, J. E., Catanzaro, A., Geertsma, F., Hoover, S. E., Johnson, R. H., Kusne,
S., Lisse, J., MacDonald, J. D., Meyerson, S. L., Raksin, P. B., Siever, J., Stevens, D. A., Sunenshine, R.,
Theodore, N. Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the
Treatment of Coccidioidomycosis. Clin. Infect. Dis., 2016 63,112-146.
Galgiani, J. N., Payne, C. M. Leukocyte Effects on the Dimorphism of
Coccidioides immitis. J. Infect. Dis., 1982 146, 56-63.
Gastélum-Cano, J. M., Dautt-Castro, M., García-Galaz, A., Felix-Murray, K., Rascón-Careaga, A., Cano Rangel,
M. A., Islas-Osuna, M. A. The Clinical Laboratory Evolution in Coccidioidomycosis Detection:
Future Perspectives. J. Med. Mycol., 2021 31, 101159.
Gorris, M. E., Caballero, V. D. M. C., Carey, A., Hamm, P. S., Mead, H. L., Uehling, J. K. A Review of
Coccidioides Research, Outstanding Questionsin the Field, and Contributions by Women Scientists. Curr.
Clin. Microbiol. Rep., 2021 8, 114-128.
Graupmann-Kuzma, A., Valentine, B. A., Shubitz, L. F., Dial, S. M., Watrous, B., Tornquist, S. J.
Coccidioidomycosis in Dogs and Cats: A Review. J. Am. Anim. Hosp. Assoc., 2008 44, 226-235.
Grizzle, A. J., Wilson, L., Nix, D. E., Galgiani, J. N. Clinical and Economic Burden of Valley Fever in Arizona:
In Incidence-Based Cost-Of-Illness Analysis. Open Forum Infect. Dis., 2020 8, ofaa623.
Hung, C. Y., Hsu, A. P., Holland, S. M., Fierer, J. A Review of Innate and Adaptive Immunity to
Coccidioidomycosis. Med. Mycol., 2019 57, S85-S92.
Johnson, R. H., Sharma, R., Kuran, R., Fong, I., Heidari, A. Coccidioidomycosis:
A Review. J. Investig. Med., 2021 69, 316-323.
Kirkland, T. N., Fierer, J. Coccidioides immitis and posadasii: A Review of their Biology, Genomics,
Pathogenesis, and Host Immunity. Virulence, 2018 9, 1426-1435.
Kollath, D. R., Miller, K. J., Barker, B. M. The Mysterious Desert Dwellers: Coccidioides immitis and
Coccidioides posadasii, Causative Fungal Agents of Coccidioidomycosis. Virulence, 2019 10, 222-233.
Kollath, D. R., Teixeira, M. M., Funke, A., Miller, K. J., Barker, B. M. Investigating the Role of Animal
Burrows on the Ecology and Distribution of Coccidioides spp. in Arizona Soils. Mycopathologia, 2019
176, 139-148.
Laniado-Laborín, R., Arathoon, E. G., Canteros, C., Muñiz-Salazar, R., Rendon, A.
Coccidioidomycosis in Latin America. Med. Mycol., 2019 57, S46-S55.
Ophuls, W., Moffitt, H. A New Pathogenic Mould (Formerly Described as a Protozoon:
Coccidioides immitis pyogenes): Preliminary Report. Phila. Med., 1900 5, 1471-1472.
Patel, R. A Moldy Application of MALDI: MALDI-Tof Mass Spectrometry for
Fungal Identification. J. Fungi, 2019 5, 4.
Peng, T., Zong, Y., Johnson, M. D., Menghani, S. V., Lewis, M. L., Galgiani, J. N. A Quantitative Enzyme
Linked Immunoassay (ELISA) to Approximate Complement-Fixing Antibody Titers in Serum from
Patients with Coccidioidomycosis. Diagn. Microbiol. Infect. Dis., 2021 99, 115198.
Reyes-Montes, M. R., Frías-De-León, M. G., Victoriano-Pastelín, I., Acosta-Altamirano, G., Duarte-Escalante,
E. Design and Evaluation of an AFLP Molecular Marker for the Detection of Coccidioides spp. in
Biological Samples. Braz. J. Infect. Dis., 2019 23, 322-330.
Rixford, E., Gilchrist, T. Two Cases of Protozoan (Coccidioidal) Infection of the Skin and Other Organs.
Johns Hopkins Hosp. Rpts., 1896 1, 209-268.
Saubolle, M. A., McKellar, P. P., Sussland, D. Epidemiologic, Clinical, and Diagnostic Aspects of
Coccidioidomycosis. J. Clin. Microbiol., 2007 45,26-30.
Saubolle, M. A., Wojack, B. R., Wertheimer, A. M., Fuayagem, A. Z., Young, S., Koeneman, B. A. Multicenter
Clinical Validation of a Cartridge-Based Real-Time PCR System for Detection of Coccidioides spp. in
Lower Respiratory Specimens. J. Clin. Microbiol., 2018 56, e01277-17.
Sharpton, T. J., Stajich, J. E., Rounsley, S. D., Gardner, M. J., Wortman, J. R., Jordar, V. S., Maiti, R., Kodira,
C. D., Neafsey, D. E., Zeng, Q., Hung, C. Y., McMahan, C., Muszewska, A., Grynberg, M., Mandel, M.
A., Kellner, E. M., Barker, B. M., Galgiani, J. N., Orbach, M. J., Kirkland, T. N., Cole, G. T., Henn, M.
R., Birren, B. W., Taylor, J. W. Comparative Genomic Analyses of the Human Fungal Pathogens
Coccidioides and their Relatives. Genome Res., 2009 19, 1722-1731.
Singh, K. Laboratory Acquired Infections. Clin. Infect. Dis., 2009 49, 142-147.
Smith, C. E., Beard, R. R. Varieties of Coccidioidal Infection in Relation to the Epidemiology
and Control of the Diseases. Am. J. Public. Health., 1946 36, 1394-1402.
Smith, C. E., Beard, R. R., Rosenberger, H. G., Whiting, E. G. Effect of Season and Dust Control on
Coccidioidomycosis. J. Am. Med. Assoc., 1946 132, 833-838.
Smith, C. E., Saito, M. T., Simons, S. A. Pattern of 39,500 Serologic Tests in
Coccidioidomycosis. J. Am. Med. Assoc., 1956 160, 546-552.
Stevens, D. A., Shatsky, S. A. Intrathecal Amphotericin in the Management of
Coccidioidal Meningitis. Semin. Respir. Infect., 2001 16, 263-269.
Stockman, L., Clark, K. A., Hunt, J. M., Roberts, G. D. Evaluation of Commercially Available Acridinium
Ester-Labeled Chemiluminescent DNA Probes for Culture Identification of Blastomyces dermatitidis,
Coccidioides immitis, Cryptococcus neoformans, and Histoplasma capsulatum.
J. Clin. Microbiol., 1993 31, 845-850.
Taylor, J. W., Barker, B. M. The Endozoan, Small-Mammal Reservoir Hypothesis and the Life Cycle of
Coccidioides Species. Med. Mycol., 2019 57, S16-S20.
Taylor, J. W., Fisher, M. C. Fungal Multilocus Sequence Typing – It’s Not Just for Bacteria. Curr. Opin.
Microbiol., 2003 6, 351-356.
Thompson, G. R., Lewis, J. S., Nix, D. E., Patterson, T. F. Current Concepts and Future Directions in the
Pharmacology and Treatment of Coccidioidomycosis. Med. Mycol., 2019 57, S76-S84.
Tintelnot, K., De Hoog, G. S., Antweiler, E., Losert, H., Seibold, M., Brandt, M. A., Gerrits van den Ende, A.
H. G., Fisher, M. C. Taxonomic and Diagnostic Markers for Identification of Coccidiodes immitis and
Coccidiodes posadasii. Med. Mycol., 2007 45, 385-393.
Umeyama, T., Sano, A., Kamei, K., Niimi, M., Nishimura, K., Uehara, Y. Novel Approach to Designing
Primers for Identification and Distinction of the Human Pathogenic Fungi Coccidioides immitis and
Coccidioides posadasii by PCR Amplification. J. Clin. Microbiol., 2006 44, 1859-1862.
Walsh, T. J., McCarthy, M. W. The Expanding Use of Matrix-Assisted Laser Desorption/Ionization-Time of
Flight Mass Spectroscopy in the Diagnosis of Patients with Mycotic Diseases.
Expert. Rev. Mol. Diagn., 2019 19, 241-248.


Publish with Nova Science Publishers

We publish over 800 titles annually by leading researchers from around the world. Submit a Book Proposal Now!