A case study of disseminated coccidioidomycosis following anti-TB treatment

A case study of disseminated coccidioidomycosis following anti-TB treatment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A case study of disseminated coccidioidomycosis following anti-TB treatment Gabriel Palma-Cortés, Marcela Verónica Muñoz-Torrico, Julio Santiago, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7964133/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Mycobacterium and Coccidioides are pathogenic microorganisms that can provoke progressive pulmonary or disseminated granulomatous diseases in humans. Tuberculosis (TB) and coccidioidomycosis have similar clinical and radiological presentations but require different treatments. Coinfection with TB and Coccidioides is exceptionally rare. Diagnosis may be missed even in endemic areas. Case presentation : We present the case of a 34-year-old immunocompetent man with no previous history of TB exposure. Initially, microbiological and molecular tests were positive for Mycobacterium tuberculosis, which showed resistance to rifampicin, and he was discharged with TB treatment. However, after 27 days, he returned with abscesses on his head, left knee, shoulder, and left forefinger. Direct examination of the lesions with KOH and Grocott stain then revealed multiple endospore-containing spherules, confirming coccidioidomycosis. The fungus was further genotyped as Coccidioides posadasii using 621 and GAC microsatellites. Treatment with antimycotic drugs (fluconazole and amphotericin B) led to improvement of the patient's chest X-ray and lesions after several weeks. Conclusions : Though coinfection by Coccidioides and Mycobacterium is extremely rare, it can occur in immunocompetent patients exposed in endemic regions like northern Mexico. Treatment of tuberculosis with antimicrobials may mask or complicate the coccidioidomycosis diagnosis. Early diagnosis and intervention with antifungals such as amphotericin B and fluconazole can significantly improve clinical outcomes. Disseminated coccidioidomycosis valley fever tuberculosis anti-TB treatment Coccidioides posadasii Mycobacterium tuberculosis amphotericin B deoxycholate drug combination antifungal treatment abscess coinfection pathogenesis Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Coccidioides and Mycobacterium are pathogens that can cause progressive pulmonary or disseminated granulomatous disease in humans [ 1 ]. Both infections share similar clinical and radiological outcomes, which can lead to diagnostic confusion [ 2 ] and complicate pharmacological therapy. Coccidioides is a dimorphic fungus. Its saprophytic (infective) phase produces mycelium-derived arthroconidia, while its parasitic phase forms endospore-containing sphaerules [ 3 ]. The saprophytic phase inhabits dry, alkaline soils in semi-arid regions of North America. Arthroconidia are commonly found near animal burrows that have harbored the parasitic phase [ 4 ]. Coccidioidomycosis is endemic to the semi-arid areas in the southwestern United States and northern Mexico, specifically in the Lower Sonoran Life Zone at the US-Mexico border [ 5 ], where most cases are reported. It also occurs in isolated regions of Central and South America. Rare cases outside endemic areas are mostly imported [ 6 , 7 ]. C. immitis is restricted to southern California and northern Baja California, while C. posadasii is present in the rest of the USA, Mexico, Brazil, and Argentina [ 8 ]. Tuberculosis (TB) is caused by acid-fast, gram-positive actinobacteria of the Mycobacterium tuberculosis complex (MTBC) [ 9 ]. It is distributed worldwide and transmitted through contaminated aerosol droplets expelled by cough from infected individuals [ 10 ]. In healthy individuals, the mycobacteria are usually contained by granuloma formation in the lung, and remain dormant. When immune competence is compromised, active infection is established, and the bacteria can disseminate to other organs [ 11 ]. The northern border states of Mexico have the country's highest TB rates. This area overlaps with the region where coccidioidomycosis is endemic [ 12 ]. The coexistence of coccidioidomycosis and TB has been described in the USA since the 1940s. Recent reports show Coccidioides infection may be diagnosed when clinical conditions fail to improve after anti-TB treatment [ 13 , 14 ]. In this report, we describe a case of coinfection where coccidiodomycosis was exacerbated and diagnosed after successful TB treatment. Possible risk factors and clinical management are discussed. Case presentation A 34-year-old immunocompetent male with residence in Mexico City’s conurbation arrived at the emergency service of a third-level hospital (Hospital General “Dr. Manuel Gea González”) with fatigue, weakness, and malnutrition. The patient was referred to the National Institute of Respiratory Diseases (INER) with a primary diagnosis of drug-resistant tuberculosis. He reported an 11-month disease course with haemoptysis, left ear fullness, and fever, dyspnea, and severe weight loss (BMI = 13.5). Blood exams indicated hypovolemia, hyponatremia, lymphocytopenia (11.30%), metabolic acidosis, hepatic dysfunction (ALT values of 29 UI/L), and severe malnutrition (1.76 g/dL albumin). The patient had a twenty-year history of addiction to tobacco and fifteen years of abuse of alcohol, marijuana, solvents, cocaine, and crack, but reported five years of rehabilitation. The bacilloscopy, culture, and GeneXpert tests demonstrated the presence of multidrug-resistant mycobacteria. HIV and HCV tests were negative. A second-line anti-tuberculosis treatment was initiated following the Directly Observed Treatment, Short-course strategy (DOTS). It consisted of isoniazid (300 mg/24hr), levofloxacin (750 mg/24hr), amikacin (750 mg/24hr), prothionamide (750 mg/24hr), cycloserine (250 mg/24hr), pyrazinamide (1600 mg/12hr), and ethambutol (1200 mg/24hr). After 27 days of hospitalization, the patient was discharged, having shown an improvement in general condition and negative bacilloscopy. The patient returned to the hospital 22 days later, reporting abscesses and joint pain. He presented with volume gain in the frontal and bilateral malar regions, as well as in the right second toe, and erythema in the right knee and the left ankle. Other symptoms were asthenia, adynamia, weight loss, and fever. The radiological analysis presented multicavitary lung opacities with a bilateral diffuse reticular-nodular medium and intraclavicular hilum predominance (Fig. 1 ). A Ga67 whole-body scan performed with a SPECT/CT Symbia T2 (Siemens) allowed the identification of extrapulmonary foci of coccidioidomycosis infection in different places of the body (Fig. 2 ). Samples of the synovial abscess (Fig. 3 ) and of maxillofacial secretion were examined for the presence of fungi. Grocott silver stain revealed the presence of endospore-containing spherules; spore germination with septate hyphae and arthroconidia was observed after ten days of culture (Fig. 4 ). Endospore-containing spherules were also observed in histologic analysis of splenectomy samples (Fig. 3 ). The findings were unconventional as the patient was born and resided in the central region of the country, in locations where Coccidioides is not endemic; however, he reported having been employed as a construction worker and driver in the northern states of Nuevo León, Sonora, and Coahuila for more than three years. In concordance with the mycological analysis, the Delayed-Type Hypersensitivity Skin Testing for coccidioidomycosis was positive with a 40 mm induration. Tube precipitin-type antibody testing produced a positive titer of 1:8. The Ouchterlony double immunodiffusion test for IgG gave a positive result, and genotypification of the fungus isolated from culture was achieved by PCR amplification of two microsatellite-containing loci named GAC and 621 and served to identify the isolate as belonging to the species C. posadasii [ 15 ]. The patient was treated with antimycotic drugs, fluconazole (800 mg/day) and amphotericin B (0.7-1 mg/kg/day), and showed improvement in both conditions. One year later, he was in the sterilizing phase of the TB treatment, but he abandoned the hospital monitoring. Discussion and conclusions The radiological pattern of coccidioidomycosis is not specific. The disease has an ample clinical spectrum from a non-manifested infection or a mild primary respiratory disease to a chronic pulmonary disease or an acute disseminated extrapulmonary infection [ 2 ]. Taking this into account, the presumptive diagnosis at arrival is commonly associated with tuberculosis (up to 90% in the hospital where the present case was disclosed) and, less frequently, with neoplasia; even when a mycotic illness is suspected, the diagnosis is commonly ascribed to histoplasmosis or aspergillosis. In Mexico, in contrast with Arizona, the report of Coccidioides cases is not mandatory, in spite of the shared risks and importance of the disease [ 16 ]. As a consequence, serological or culture tests for Coccidioides are not included in routine laboratory exams, either in primary care pneumology services or in third-level national hospitals. This is partly explained by the biosafety risk imposed by the culture of this species. A genetic determination approach is much less achievable, but it would be relevant for the epidemiological surveillance in cases of disseminated disease. Here, we decided to genotype the samples obtained from the biopsies, after noting the patient's migration history, to investigate the origin of the strain involved. The assignment to C. posadasii is in agreement with the hypothesis of the acquisition of the infection in the north of the country and suggests that the infection was not acquired de novo during the month elapsed between the first and second hospitalizations, but that it is more probably a case of coinfection. Although there are few case reports on Mycobacterium and Coccidioides coexistence, we strongly emphasize the need for nationwide regulation to facilitate early detection of Coccidioides in tuberculosis cases. We recommend that tuberculosis patients with a history of travel to endemic locations, or with other identified risk factors, undergo serological screening for Coccidioides. Each suspected case should be assessed rigorously on an individual basis to account for the specific combination of risk factors present. This patient had three risk factors: male gender, residence in an endemic region, and employment as a construction worker [ 8 ]. Ethnicity was likely not a risk factor. The risk of coccidioidomycosis in individuals with a history of drug abuse or malnutrition, both of which are present in this patient, remains poorly described. These factors deserve closer study. If in the presence of a possible disseminated TB threat, and in the absence of appropriate culture facilities, physicians must often face some treatment dilemmas. They must choose either immediate antibiotic treatment or wait for Coccidioides confirmation. The slow growth rate of Coccidioides in culture media, which would imply long waiting times until treatment initiation, advises against the diagnostic by isolation. However, once initiated, antibiotics used to treat Mycobacterium infections could mask the presence of Coccidioides, as suggested by reports demonstrating diminished in vitro growth of Coccidioides with isoniazid, rifampicin, and ethambutol [ 17 , 18 ]. Anti-bacterial treatment alone is insufficient to contain a coccidioidomycosis infection, which only recedes with the use of antifungals. An inappropriate medication may then confront similar ethical issues. Based on the in vitro evidence, the parallel use of antibiotics and antimycotics for coccidioidomycosis should bring about therapeutic benefits, as a synergism between anti-TB drugs and antifungals to eliminate the fungus has been reported. However, the combination of itraconazole and rifampicin did not show that synergic effect [ 19 ]. Although the coexistence of both pathogens is possible, recent studies have reported patients with both active TB and coccidioidomycosis [ 20 , 21 ]; a case of anti-TB drugs prompting Coccidioides exacerbation has not been reported to date. Furthermore, while both can present with similar lung cavities, treating one can be complicated if the other is not appropriately managed. So, the underlying processes by which coccidioidomycosis might be exacerbated after successful TB treatment remain to be investigated; possibly, therapy alter the immunological or microbiological environment, enabling of accelerating the onset or spread of Coccidioides infection; further than, lung damage caused by TB [ 20 ], an immunocompromised immune system [ 14 , 22 ], and other conditions could be increasing risk factors. In conclusion, coinfection by Coccidioides and Mycobacterium is extremely rare. It can occur in immunocompetent patients with a history of exposure in endemic regions, such as northern Mexico. Coccidioidomycosis may be underdiagnosed or diagnosed late in patients with tuberculosis, due to the similarity in its clinical and radiological presentations, and the lack of specific tests in local health systems, making it necessary to implement more rigorous surveillance and diagnostic programs. Treatment of tuberculosis with antimicrobials may mask or complicate the diagnosis of coccidioidomycosis, but early diagnosis and intervention with antifungals such as amphotericin B can significantly improve clinical outcomes. Abbreviations ALT. Alanine transaminase. BMI. Body mass index. CT. Computed Tomography. DOTS. Directly Observed Treatment, Short-course strategy. HCV. Hepatitis C virus. HIV. Human immunodeficiency virus. INER. National Institute of Respiratory Diseases. MTBC. Mycobacterium tuberculosis complex. PCR. Polymerase chain reaction. TB. tuberculosis. Declarations Patient consent for publication: Written informed consent was obtained from the patient for publication of this case report and accompanying images. Ethics considerations: Patient confidentiality was thoroughly safeguarded, and personal data was managed in a manner that precluded patient identification. All procedures performed in this study involving human participants were in accordance with the ethical standards of the Research and Ethics Committee for the National Institute of Respiratory Diseases (INER) and with the 1964 Helsinki Declaration. Competing interests: The authors declare that they have no competing interests. Funding : This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Availability of data and materials. Not applicable. Contributors : GPC: isolated the fungus and characterized the strain of Coccidioides, also prepared figure 4; MVMT: managed the patient and clinical data, and prepared figures 1-3; JS reviewed the design of the study and the literature, and wrote the main manuscript text; FHS, DPRO, HTG: reviewed the literature and wrote the manuscript text; LAND, FRMV: participated in interpreting the patient’s laboratory results and prepared figures 1-2; CCG: reviewed the manuscript, and prepare figure 4. All authors read and approved the manuscript. CARE guidelines were adhered to. Acknowledgements: We thank all those physicians and nurses who participated in the management of the patient. References Cox RA, Magee DM (2004). Coccidiodomycosis: host response and vaccine development. Clin Microbiol Rev 17:804-39. https://doi.org/ 10.1128/CMR.17.4.804-839.2004 Muñoz-Hernández B, Martínez-Rivera MA, Palma-Cortés G, Tapia-Díaz A, Manjarrez-Zavala ME (2008). Mycelial forms of Coccidioides spp. in the parasitic phase associated to pulmonary coccidioidomycosis with type 2 diabetes mellitus. Eur J Clin Microbiol Infect Dis 27:813-20. https://doi.org/10.1007/s10096-008-0508-4 Welsh O, Vera-Cabrera L, Rendon A, González G, Bonifaz A (2012). Coccidioidomycosis. Clin Dermatol 30:573-91. https://doi.org/10.1016/j.clindermatol.2012.01.003 Reyes-Montes MR, Pérez-Huitrón MA, Ocaña-Monroy JL, Frías-De-León MG, Martínez-Herrera E, et al. (2016). The habitat of Coccidioides spp. and the role of animals as reservoirs and disseminators in nature. BMC Infectious Diseases 16:1-8. https://doi.org/10.1186/s12879-016-1902-7 Hector RF, Laniado-Laborin R (2005). Coccidioidomycosis-a fungal disease of the Americas. PLoS Med 2:e2. https://doi.org/10.1371/journal.pmed.0020002 Desai NR, McGoey R, Troxclair D, Simeone F, Palomino J (2010). Coccidioidomycosis in nonendemic area: case series and review of literature. J La State Med Soc 162:97-103. Wang ZY1, Wen SL, Ying KJ (2011). A case study of imported pulmonary coccidioidomycosis. J Zhejiang Univ Sci B 12:298-302. https://doi.org/10.1631/jzus.B1000261 Brown J, Benedict K, Park BJ, Thompson GR 3rd (2013). Coccidioidomycosis: epidemiology. Clin Epidemiol 5:185-7. https://doi.org/10.2147/CLEP.S34434 Forrellad MA, Klepp LI, Gioffré A, Sabio y García J, Morbidoni HR et. al (2013). Virulence factors of the Mycobacterium tuberculosis complex. Virulence 4:3–66. https://doi.org/10.4161/viru.22329 Smith I (2003). Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbiol Rev 16:463–96. https://doi.org/10.1128/CMR.16.3.463-496.2003 Gengenbacher M, Kaufmann SH (2012). Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev 2012;36:514-32. https://doi.org/10.1111/j.1574-6976.2012.00331.x Oren E, Alatorre-Izaguirre G, Vargas-Villarreal J, Moreno-Treviño MG, Garcialuna-Martínez J et al. (2015). Interferon Gamma-Based Detection of Latent Tuberculosis Infection in the Border States of Nuevo Leon and Tamaulipas, Mexico. Front Public Health 2015;3:220. https://doi.org/10.3389/fpubh.2015.00220 Cadena J, Hartzler A, Hsue G, Longfield RN (2009). Coccidioidomycosis and tuberculosis coinfection at a tuberculosis hospital: clinical features and literature review. Medicine (Baltimore) 88:66-76. https://doi.org/10.1097/MD.0b013e318194757a Silva-Hernández AG, Barbachano-Rodríguez E, Alanís-Miranda PA, González-Martínez MR, Portales-Castanedo A (2010). Tuberculosis and coccidiodomycosis in two patients without immune acquired deficiency. Rev Med Inst Mex Seguro Soc 48:447-52. Luna-Isaac JA, Muñiz-Salazar R, Baptista-Rosas RC, Enríquez-Paredes LM, Castañón-Olivares LR et al. (2014). Genetic analysis of the endemic fungal pathogens Coccidioides posadasii and Coccidioides immitis in Mexico. Medical Mycol 52:156-66. https://doi.org/10.1093/mmy/myt005 Laniado-Laborin R (2007). Expanding understanding of epidemiology of coccidioidomycosis in the Western hemisphere. Ann NY Acad Sci 1111:19–34. https://doi.org/10.1196/annals.1406.004 de Aguiar Cordeiro R, Brilhante RS, Rocha MF, Fechine MA, Camargo ZP, et al. (2006). In vitro inhibitory effect of antituberculosis drugs on clinical and environmental strains of Coccidioides posadasii. J Antimicrob Chemother 58:575-9. https://doi.org/10.1093/jac/dkl290 Cordeiro R de A, de Melo CV, Marques FJ, Serpa R, Evangelista AJ et al. (2016). Synthesis and in vitro antifungal activity of isoniazid-derived hydrazones against Coccidioides posadasii . Microb Pathog 98:1-5. https://doi.org/10.1016/j.micpath.2016.06.022 Cordeiro R de A, Brilhante RS, Rocha MF, Medrano DJ, Monteiro AJ et al. (2009). In vitro synergistic effects of antituberculous drugs plus antifungals against Coccidioides posadasii . Int J Antimicrob Agents 34(3):278-80. https://doi.org/10.1016/j.ijantimicag.2009.04.009 Kattamuri L, Zambrano A, Duvvuru SR, Sharma K, Deoker A (2025). Concurrent Coccidioidomycosis and Mycobacterium abscessus Infection in ChronicObstructive Pulmonary Disease. J Investig Med High Impact Case Rep. 23247096251334229. doi:10.1177/23247096251334229. Epub 2025 Apr 28. Rojas-Rojas EA, Cinencio-Chávez WR, Laniado-Laborín R (2023). Delayed diagnosis of tuberculosis in a patient with coccidioidomycosis. Neumol Cir Torax 82(4):253-5. Cohen IM, Galgiani JN, Ogden DA (1981). Simultaneous tuberculosis and Coccidioidomycosis in end stage renal disease. Sabouraudia. 1981 19(1):13-6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7964133","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":536661242,"identity":"e14110f7-2784-477e-83a1-92663ce83bd7","order_by":0,"name":"Gabriel Palma-Cortés","email":"","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas","correspondingAuthor":false,"prefix":"","firstName":"Gabriel","middleName":"","lastName":"Palma-Cortés","suffix":""},{"id":536661243,"identity":"25823f6a-c7b1-4cb5-a61c-d75055569479","order_by":1,"name":"Marcela Verónica Muñoz-Torrico","email":"","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas","correspondingAuthor":false,"prefix":"","firstName":"Marcela","middleName":"Verónica","lastName":"Muñoz-Torrico","suffix":""},{"id":536661244,"identity":"0dbc8e11-e666-4ad8-acec-2b05bb91fce6","order_by":2,"name":"Julio Santiago","email":"data:image/png;base64,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","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas","correspondingAuthor":true,"prefix":"","firstName":"Julio","middleName":"","lastName":"Santiago","suffix":""},{"id":536661245,"identity":"853cf04d-a9d9-409b-88a4-3fc6e1bd99e8","order_by":3,"name":"Fernando Hernández-Sánchez","email":"","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas","correspondingAuthor":false,"prefix":"","firstName":"Fernando","middleName":"","lastName":"Hernández-Sánchez","suffix":""},{"id":536661246,"identity":"d3b5b7af-7e7a-4789-8b2b-763cd0824446","order_by":4,"name":"Dora Patricia Rosete-Olvera","email":"","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas","correspondingAuthor":false,"prefix":"","firstName":"Dora","middleName":"Patricia","lastName":"Rosete-Olvera","suffix":""},{"id":536661247,"identity":"4c40d047-dd91-4508-9a39-188ce84124d1","order_by":5,"name":"Haydee Torres-Guerrero","email":"","orcid":"","institution":"Universidad Nacional Autónoma de México","correspondingAuthor":false,"prefix":"","firstName":"Haydee","middleName":"","lastName":"Torres-Guerrero","suffix":""},{"id":536661248,"identity":"4455d130-97d5-4060-bf31-b10242b9f073","order_by":6,"name":"Luis Armando Narváez-Díaz","email":"","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas","correspondingAuthor":false,"prefix":"","firstName":"Luis","middleName":"Armando","lastName":"Narváez-Díaz","suffix":""},{"id":536661249,"identity":"b1b4c0a4-4468-4559-b445-8d15d4b4b58e","order_by":7,"name":"Fernando Rosario Morales-Villareal","email":"","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas","correspondingAuthor":false,"prefix":"","firstName":"Fernando","middleName":"Rosario","lastName":"Morales-Villareal","suffix":""},{"id":536661250,"identity":"bcb0a852-a64d-4c10-b8c2-3027cb612c9c","order_by":8,"name":"Carlos Cabello-Gutiérrez","email":"","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas","correspondingAuthor":false,"prefix":"","firstName":"Carlos","middleName":"","lastName":"Cabello-Gutiérrez","suffix":""}],"badges":[],"createdAt":"2025-10-28 05:21:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7964133/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7964133/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95444551,"identity":"ba6ea7e7-aa67-472b-aa32-41e33a4421bb","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":325120,"visible":true,"origin":"","legend":"","description":"","filename":"15AcasestudydissemincoccidtxTBPalmaetalENVIADOFFFF.doc","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/4c51fca6fb9032de29681138.doc"},{"id":95444552,"identity":"4b0d4712-217b-4294-9b03-cf003d528bf7","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":9975,"visible":true,"origin":"","legend":"","description":"","filename":"1705b54c896e4652a7b8491ee14914aa.json","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/37bb48af783a75bd337141bf.json"},{"id":95444547,"identity":"cf2554eb-8c88-4397-b94d-627dc39f64eb","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":64811,"visible":true,"origin":"","legend":"","description":"","filename":"1705b54c896e4652a7b8491ee14914aa1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/2a722aa3c3e40816c5e42f9d.xml"},{"id":95444549,"identity":"e780eb6f-5d53-4bbd-8025-24d3576809b9","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73019,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/50a4e77e9093b18da505b352.jpeg"},{"id":95444556,"identity":"b48745bb-f828-4a88-af56-67b7b4698572","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":40997,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/d8dff1664abce3d24107b051.jpeg"},{"id":95444554,"identity":"9942d6a9-a250-4a91-81b9-d54b18bd844b","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":45457,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/430dab4bef7e9d6e5dbe0566.jpeg"},{"id":95444560,"identity":"684dfc86-7a7a-4719-85d3-680d0acdf367","added_by":"auto","created_at":"2025-11-08 15:25:44","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":83022,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/499497f823f7276bdd701f94.jpeg"},{"id":95444555,"identity":"708c0842-0fce-434c-8ee7-31a02685ad18","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":144393,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/5e14b1e22b0d7975d0ac3405.png"},{"id":95527050,"identity":"33cb4f4f-5d0e-43a4-90c7-5e66f39e5a95","added_by":"auto","created_at":"2025-11-10 10:09:14","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":42195,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/05be48d4fffdec68407eecef.png"},{"id":95444553,"identity":"24a01d3d-8315-4a29-89f2-9947499a3eac","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":35562,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/ba1fed53494b5237e6e94972.png"},{"id":95527770,"identity":"087b61e6-d147-4299-a514-22acfbd93590","added_by":"auto","created_at":"2025-11-10 10:14:46","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74150,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/cdb4e99920f00d71974695eb.png"},{"id":95444559,"identity":"e35369b5-3cb1-496a-bef8-53d62818b4e1","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"xml","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":63067,"visible":true,"origin":"","legend":"","description":"","filename":"1705b54c896e4652a7b8491ee14914aa1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/75eef3286abd76047896d0f6.xml"},{"id":95444562,"identity":"8f0a95c8-7301-44ac-9526-5cb2a6462781","added_by":"auto","created_at":"2025-11-08 15:25:44","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72289,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/d26aeb4c67433504d9a02ebc.html"},{"id":95444548,"identity":"4b89c9ee-699d-4560-85b3-406a568eab21","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":460411,"visible":true,"origin":"","legend":"\u003cp\u003eCT scan showing cavitary injuries with bilateral micro- and macronodular lung pattern and bronchiectasis.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/4c868ab631c444d84a1a4625.png"},{"id":95444546,"identity":"1fb47733-6487-415d-bd38-65eab371d5be","added_by":"auto","created_at":"2025-11-08 15:25:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":421249,"visible":true,"origin":"","legend":"\u003cp\u003eGa67 whole-body scan performed with a SPECT/CT Symbia T2 (Siemens). Extrapulmonary foci of coccidioidomycosis infection are observed.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/1eb036282ec8c3166edc2b9d.png"},{"id":95527015,"identity":"bfec019f-a1f2-4708-94c4-634df0e8af4a","added_by":"auto","created_at":"2025-11-10 10:09:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":298072,"visible":true,"origin":"","legend":"\u003cp\u003ea) Abscesses in the malar and frontal region of the face. b) Increase in right-knee volume. c) Abscess in the second right toe with pain and erythema.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/84f1eb33010decb6ed2a04fe.png"},{"id":95527021,"identity":"446729ec-2603-44db-b9ff-381a84d39254","added_by":"auto","created_at":"2025-11-10 10:09:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":451045,"visible":true,"origin":"","legend":"\u003cp\u003eMicrographs of: a) Abscess drain samples with multiple endospore-containing spherules in KOH 10%, 10X. b) Spleen biopsy: spherule with multiple endospores is observed, Grocott, 40X. c) Arthroconidia culture in lactophenol blue, 40X.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/91aec0d063097a2cbc2f72d3.png"},{"id":95654064,"identity":"8d5457de-3990-4638-bd2c-8fcd62beb4c8","added_by":"auto","created_at":"2025-11-11 16:09:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2574483,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7964133/v1/f33231b2-fa2d-41c1-b2e6-5f255a3cc772.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case study of disseminated coccidioidomycosis following anti-TB treatment","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eCoccidioides\u003c/em\u003e and \u003cem\u003eMycobacterium\u003c/em\u003e are pathogens that can cause progressive pulmonary or disseminated granulomatous disease in humans [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Both infections share similar clinical and radiological outcomes, which can lead to diagnostic confusion [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and complicate pharmacological therapy. \u003cem\u003eCoccidioides\u003c/em\u003e is a dimorphic fungus. Its saprophytic (infective) phase produces mycelium-derived arthroconidia, while its parasitic phase forms endospore-containing sphaerules [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The saprophytic phase inhabits dry, alkaline soils in semi-arid regions of North America. Arthroconidia are commonly found near animal burrows that have harbored the parasitic phase [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Coccidioidomycosis is endemic to the semi-arid areas in the southwestern United States and northern Mexico, specifically in the Lower Sonoran Life Zone at the US-Mexico border [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], where most cases are reported. It also occurs in isolated regions of Central and South America. Rare cases outside endemic areas are mostly imported [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. \u003cem\u003eC. immitis\u003c/em\u003e is restricted to southern California and northern Baja California, while \u003cem\u003eC. posadasii\u003c/em\u003e is present in the rest of the USA, Mexico, Brazil, and Argentina [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTuberculosis (TB) is caused by acid-fast, gram-positive actinobacteria of the \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e complex (MTBC) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. It is distributed worldwide and transmitted through contaminated aerosol droplets expelled by cough from infected individuals [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In healthy individuals, the mycobacteria are usually contained by granuloma formation in the lung, and remain dormant. When immune competence is compromised, active infection is established, and the bacteria can disseminate to other organs [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The northern border states of Mexico have the country's highest TB rates. This area overlaps with the region where coccidioidomycosis is endemic [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe coexistence of coccidioidomycosis and TB has been described in the USA since the 1940s. Recent reports show \u003cem\u003eCoccidioides\u003c/em\u003e infection may be diagnosed when clinical conditions fail to improve after anti-TB treatment [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In this report, we describe a case of coinfection where coccidiodomycosis was exacerbated and diagnosed after successful TB treatment. Possible risk factors and clinical management are discussed.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 34-year-old immunocompetent male with residence in Mexico City’s conurbation arrived at the emergency service of a third-level hospital (Hospital General “Dr. Manuel Gea González”) with fatigue, weakness, and malnutrition. The patient was referred to the National Institute of Respiratory Diseases (INER) with a primary diagnosis of drug-resistant tuberculosis. He reported an 11-month disease course with haemoptysis, left ear fullness, and fever, dyspnea, and severe weight loss (BMI = 13.5). Blood exams indicated hypovolemia, hyponatremia, lymphocytopenia (11.30%), metabolic acidosis, hepatic dysfunction (ALT values of 29 UI/L), and severe malnutrition (1.76 g/dL albumin). The patient had a twenty-year history of addiction to tobacco and fifteen years of abuse of alcohol, marijuana, solvents, cocaine, and crack, but reported five years of rehabilitation. The bacilloscopy, culture, and GeneXpert tests demonstrated the presence of multidrug-resistant mycobacteria. HIV and HCV tests were negative. A second-line anti-tuberculosis treatment was initiated following the Directly Observed Treatment, Short-course strategy (DOTS). It consisted of isoniazid (300 mg/24hr), levofloxacin (750 mg/24hr), amikacin (750 mg/24hr), prothionamide (750 mg/24hr), cycloserine (250 mg/24hr), pyrazinamide (1600 mg/12hr), and ethambutol (1200 mg/24hr). After 27 days of hospitalization, the patient was discharged, having shown an improvement in general condition and negative bacilloscopy.\u003c/p\u003e\u003cp\u003eThe patient returned to the hospital 22 days later, reporting abscesses and joint pain. He presented with volume gain in the frontal and bilateral malar regions, as well as in the right second toe, and erythema in the right knee and the left ankle. Other symptoms were asthenia, adynamia, weight loss, and fever. The radiological analysis presented multicavitary lung opacities with a bilateral diffuse reticular-nodular medium and intraclavicular hilum predominance (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A Ga67 whole-body scan performed with a SPECT/CT Symbia T2 (Siemens) allowed the identification of extrapulmonary foci of coccidioidomycosis infection in different places of the body (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSamples of the synovial abscess (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) and of maxillofacial secretion were examined for the presence of fungi. Grocott silver stain revealed the presence of endospore-containing spherules; spore germination with septate hyphae and arthroconidia was observed after ten days of culture (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eEndospore-containing spherules were also observed in histologic analysis of splenectomy samples (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The findings were unconventional as the patient was born and resided in the central region of the country, in locations where \u003cem\u003eCoccidioides\u003c/em\u003e is not endemic; however, he reported having been employed as a construction worker and driver in the northern states of Nuevo León, Sonora, and Coahuila for more than three years. In concordance with the mycological analysis, the Delayed-Type Hypersensitivity Skin Testing for coccidioidomycosis was positive with a 40 mm induration. Tube precipitin-type antibody testing produced a positive titer of 1:8. The Ouchterlony double immunodiffusion test for IgG gave a positive result, and genotypification of the fungus isolated from culture was achieved by PCR amplification of two microsatellite-containing loci named GAC and 621 and served to identify the isolate as belonging to the species \u003cem\u003eC. posadasii\u003c/em\u003e [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe patient was treated with antimycotic drugs, fluconazole (800 mg/day) and amphotericin B (0.7-1 mg/kg/day), and showed improvement in both conditions. One year later, he was in the sterilizing phase of the TB treatment, but he abandoned the hospital monitoring.\u003c/p\u003e"},{"header":"Discussion and conclusions","content":"\u003cp\u003eThe radiological pattern of coccidioidomycosis is not specific. The disease has an ample clinical spectrum from a non-manifested infection or a mild primary respiratory disease to a chronic pulmonary disease or an acute disseminated extrapulmonary infection [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Taking this into account, the presumptive diagnosis at arrival is commonly associated with tuberculosis (up to 90% in the hospital where the present case was disclosed) and, less frequently, with neoplasia; even when a mycotic illness is suspected, the diagnosis is commonly ascribed to histoplasmosis or aspergillosis. In Mexico, in contrast with Arizona, the report of \u003cem\u003eCoccidioides\u003c/em\u003e cases is not mandatory, in spite of the shared risks and importance of the disease [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. As a consequence, serological or culture tests for \u003cem\u003eCoccidioides\u003c/em\u003e are not included in routine laboratory exams, either in primary care pneumology services or in third-level national hospitals. This is partly explained by the biosafety risk imposed by the culture of this species. A genetic determination approach is much less achievable, but it would be relevant for the epidemiological surveillance in cases of disseminated disease. Here, we decided to genotype the samples obtained from the biopsies, after noting the patient's migration history, to investigate the origin of the strain involved. The assignment to \u003cem\u003eC. posadasii\u003c/em\u003e is in agreement with the hypothesis of the acquisition of the infection in the north of the country and suggests that the infection was not acquired de novo during the month elapsed between the first and second hospitalizations, but that it is more probably a case of coinfection. Although there are few case reports on \u003cem\u003eMycobacterium\u003c/em\u003e and Coccidioides coexistence, we strongly emphasize the need for nationwide regulation to facilitate early detection of \u003cem\u003eCoccidioides\u003c/em\u003e in tuberculosis cases. We recommend that tuberculosis patients with a history of travel to endemic locations, or with other identified risk factors, undergo serological screening for Coccidioides. Each suspected case should be assessed rigorously on an individual basis to account for the specific combination of risk factors present.\u003c/p\u003e\u003cp\u003eThis patient had three risk factors: male gender, residence in an endemic region, and employment as a construction worker [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Ethnicity was likely not a risk factor. The risk of coccidioidomycosis in individuals with a history of drug abuse or malnutrition, both of which are present in this patient, remains poorly described. These factors deserve closer study.\u003c/p\u003e\u003cp\u003eIf in the presence of a possible disseminated TB threat, and in the absence of appropriate culture facilities, physicians must often face some treatment dilemmas. They must choose either immediate antibiotic treatment or wait for \u003cem\u003eCoccidioides\u003c/em\u003e confirmation. The slow growth rate of \u003cem\u003eCoccidioides\u003c/em\u003e in culture media, which would imply long waiting times until treatment initiation, advises against the diagnostic by isolation. However, once initiated, antibiotics used to treat Mycobacterium infections could mask the presence of Coccidioides, as suggested by reports demonstrating diminished in vitro growth of \u003cem\u003eCoccidioides\u003c/em\u003e with isoniazid, rifampicin, and ethambutol [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Anti-bacterial treatment alone is insufficient to contain a coccidioidomycosis infection, which only recedes with the use of antifungals. An inappropriate medication may then confront similar ethical issues. Based on the in vitro evidence, the parallel use of antibiotics and antimycotics for coccidioidomycosis should bring about therapeutic benefits, as a synergism between anti-TB drugs and antifungals to eliminate the fungus has been reported. However, the combination of itraconazole and rifampicin did not show that synergic effect [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Although the coexistence of both pathogens is possible, recent studies have reported patients with both active TB and coccidioidomycosis [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]; a case of anti-TB drugs prompting \u003cem\u003eCoccidioides\u003c/em\u003e exacerbation has not been reported to date. Furthermore, while both can present with similar lung cavities, treating one can be complicated if the other is not appropriately managed. So, the underlying processes by which coccidioidomycosis might be exacerbated after successful TB treatment remain to be investigated; possibly, therapy alter the immunological or microbiological environment, enabling of accelerating the onset or spread of \u003cem\u003eCoccidioides\u003c/em\u003e infection; further than, lung damage caused by TB [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], an immunocompromised immune system [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and other conditions could be increasing risk factors. In conclusion, coinfection by \u003cem\u003eCoccidioides\u003c/em\u003e and \u003cem\u003eMycobacterium\u003c/em\u003e is extremely rare. It can occur in immunocompetent patients with a history of exposure in endemic regions, such as northern Mexico. Coccidioidomycosis may be underdiagnosed or diagnosed late in patients with tuberculosis, due to the similarity in its clinical and radiological presentations, and the lack of specific tests in local health systems, making it necessary to implement more rigorous surveillance and diagnostic programs. Treatment of tuberculosis with antimicrobials may mask or complicate the diagnosis of coccidioidomycosis, but early diagnosis and intervention with antifungals such as amphotericin B can significantly improve clinical outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eALT. Alanine transaminase.\u003c/p\u003e\n\u003cp\u003eBMI. Body mass index.\u003c/p\u003e\n\u003cp\u003eCT. Computed Tomography.\u003c/p\u003e\n\u003cp\u003eDOTS.\u0026nbsp;Directly Observed Treatment, Short-course\u0026nbsp;strategy.\u003c/p\u003e\n\u003cp\u003eHCV. Hepatitis C virus.\u003c/p\u003e\n\u003cp\u003eHIV. Human immunodeficiency virus.\u003c/p\u003e\n\u003cp\u003eINER. National Institute of Respiratory Diseases.\u003c/p\u003e\n\u003cp\u003eMTBC. \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e complex.\u003c/p\u003e\n\u003cp\u003ePCR. Polymerase chain reaction.\u003c/p\u003e\n\u003cp\u003eTB. tuberculosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003ePatient consent for publication:\u003c/strong\u003e Written informed consent was obtained from the patient for publication of this case report and accompanying images.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthics considerations: Patient confidentiality was thoroughly safeguarded, and personal data was managed in a manner that precluded patient identification.\u0026nbsp;All procedures performed in this study involving human participants were in accordance with the ethical standards of the Research and Ethics Committee for the National Institute of Respiratory Diseases (INER) and with the 1964 Helsinki Declaration.\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials.\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors\u003c/strong\u003e: GPC: isolated the fungus and characterized the strain of Coccidioides, also prepared figure 4; MVMT: managed the patient and clinical data, and prepared figures 1-3; \u0026nbsp;JS reviewed the design of the study and the literature, and wrote the main manuscript text; FHS, DPRO, HTG: reviewed the literature and wrote the manuscript text; LAND, FRMV: participated in interpreting the patient\u0026rsquo;s laboratory results and prepared figures 1-2; CCG: reviewed the manuscript, and prepare figure 4. All authors read and approved the manuscript. CARE guidelines were adhered to.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe thank all those physicians and nurses who participated in the management of the patient.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eCox RA, Magee DM (2004). Coccidiodomycosis: host response and vaccine development. Clin Microbiol Rev 17:804-39. \u003cstrong\u003ehttps://doi.org/\u003c/strong\u003e10.1128/CMR.17.4.804-839.2004\u003c/li\u003e\n \u003cli\u003eMu\u0026ntilde;oz-Hern\u0026aacute;ndez B, Mart\u0026iacute;nez-Rivera MA, Palma-Cort\u0026eacute;s G, Tapia-D\u0026iacute;az A, Manjarrez-Zavala ME (2008).\u0026nbsp;Mycelial forms of \u003cem\u003eCoccidioides\u003c/em\u003e spp. in the parasitic phase associated to pulmonary coccidioidomycosis with type 2 diabetes mellitus. Eur J Clin Microbiol Infect Dis 27:813-20. https://doi.org/10.1007/s10096-008-0508-4\u003c/li\u003e\n \u003cli\u003eWelsh O, Vera-Cabrera L, Rendon A, Gonz\u0026aacute;lez G, Bonifaz A (2012). Coccidioidomycosis. Clin Dermatol 30:573-91. https://doi.org/10.1016/j.clindermatol.2012.01.003\u003c/li\u003e\n \u003cli\u003eReyes-Montes MR, P\u0026eacute;rez-Huitr\u0026oacute;n MA, Oca\u0026ntilde;a-Monroy JL, Fr\u0026iacute;as-De-Le\u0026oacute;n MG, Mart\u0026iacute;nez-Herrera E, et al. (2016).\u0026nbsp;The habitat of \u003cem\u003eCoccidioides\u003c/em\u003e\u003cem\u003espp.\u003c/em\u003e and the role of animals as reservoirs and disseminators in nature. BMC Infectious Diseases 16:1-8. https://doi.org/10.1186/s12879-016-1902-7\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Hector RF, Laniado-Laborin R (2005).\u0026nbsp;Coccidioidomycosis-a fungal disease of the Americas. PLoS Med 2:e2. https://doi.org/10.1371/journal.pmed.0020002\u003c/li\u003e\n \u003cli\u003eDesai NR, McGoey R, Troxclair D, Simeone F, Palomino J (2010).\u0026nbsp;Coccidioidomycosis in nonendemic area: case series and review of literature. J La State Med Soc 162:97-103.\u003c/li\u003e\n \u003cli\u003eWang ZY1, Wen SL, Ying KJ (2011). A case study of imported pulmonary coccidioidomycosis. J Zhejiang Univ Sci B 12:298-302. https://doi.org/10.1631/jzus.B1000261\u003c/li\u003e\n \u003cli\u003eBrown J, Benedict K, Park BJ, Thompson GR 3rd (2013). Coccidioidomycosis: epidemiology. Clin Epidemiol 5:185-7. https://doi.org/10.2147/CLEP.S34434\u003c/li\u003e\n \u003cli\u003eForrellad MA, Klepp LI, Gioffr\u0026eacute; A, Sabio y Garc\u0026iacute;a J, Morbidoni HR et. al (2013).\u0026nbsp;Virulence factors of the Mycobacterium tuberculosis complex. Virulence 4:3\u0026ndash;66. https://doi.org/10.4161/viru.22329\u003c/li\u003e\n \u003cli\u003eSmith I (2003). Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbiol Rev 16:463\u0026ndash;96. https://doi.org/10.1128/CMR.16.3.463-496.2003\u003c/li\u003e\n \u003cli\u003eGengenbacher M, Kaufmann SH (2012). Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev 2012;36:514-32. https://doi.org/10.1111/j.1574-6976.2012.00331.x\u003c/li\u003e\n \u003cli\u003eOren E, Alatorre-Izaguirre G, Vargas-Villarreal J, Moreno-Trevi\u0026ntilde;o MG, Garcialuna-Mart\u0026iacute;nez J et al. (2015).\u0026nbsp;Interferon Gamma-Based Detection of Latent Tuberculosis Infection in the Border States of Nuevo Leon and Tamaulipas, Mexico. Front Public Health 2015;3:220. https://doi.org/10.3389/fpubh.2015.00220\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Cadena J, Hartzler A, Hsue G, Longfield RN (2009). Coccidioidomycosis and tuberculosis coinfection at a tuberculosis hospital: clinical features and literature review. Medicine (Baltimore) 88:66-76. https://doi.org/10.1097/MD.0b013e318194757a\u003c/li\u003e\n \u003cli\u003eSilva-Hern\u0026aacute;ndez AG, Barbachano-Rodr\u0026iacute;guez E, Alan\u0026iacute;s-Miranda PA, Gonz\u0026aacute;lez-Mart\u0026iacute;nez MR, Portales-Castanedo A (2010).\u0026nbsp;Tuberculosis and coccidiodomycosis in two patients without immune acquired deficiency. Rev Med Inst Mex Seguro Soc 48:447-52.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Luna-Isaac JA, Mu\u0026ntilde;iz-Salazar R, Baptista-Rosas RC, Enr\u0026iacute;quez-Paredes LM, Casta\u0026ntilde;\u0026oacute;n-Olivares LR et al. (2014).\u0026nbsp;Genetic analysis of the endemic fungal pathogens Coccidioides posadasii and Coccidioides immitis in Mexico. Medical Mycol 52:156-66. https://doi.org/10.1093/mmy/myt005\u003c/li\u003e\n \u003cli\u003eLaniado-Laborin R (2007). Expanding understanding of epidemiology of coccidioidomycosis in the Western hemisphere. Ann NY Acad Sci 1111:19\u0026ndash;34. https://doi.org/10.1196/annals.1406.004\u003c/li\u003e\n \u003cli\u003ede Aguiar Cordeiro R, Brilhante RS, Rocha MF, Fechine MA, Camargo ZP, et al. (2006). In vitro inhibitory effect of antituberculosis drugs on clinical and environmental strains of Coccidioides posadasii. J Antimicrob Chemother 58:575-9. https://doi.org/10.1093/jac/dkl290\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Cordeiro R de A, de Melo CV, Marques FJ, Serpa R, Evangelista AJ et al. (2016).\u0026nbsp;Synthesis and in vitro antifungal activity of isoniazid-derived hydrazones against \u003cem\u003eCoccidioides posadasii\u003c/em\u003e. Microb Pathog 98:1-5. https://doi.org/10.1016/j.micpath.2016.06.022\u003c/li\u003e\n \u003cli\u003eCordeiro R de A, Brilhante RS, Rocha MF, Medrano DJ, Monteiro AJ et al. (2009).\u0026nbsp;In vitro synergistic effects of antituberculous drugs plus antifungals against \u003cem\u003eCoccidioides posadasii\u003c/em\u003e. Int J Antimicrob Agents 34(3):278-80. https://doi.org/10.1016/j.ijantimicag.2009.04.009\u003c/li\u003e\n \u003cli\u003eKattamuri L, Zambrano A, Duvvuru SR, Sharma K, Deoker A (2025). Concurrent Coccidioidomycosis and \u003cem\u003eMycobacterium\u003c/em\u003e abscessus Infection in ChronicObstructive Pulmonary Disease. J Investig Med High Impact Case Rep. 23247096251334229. doi:10.1177/23247096251334229. Epub 2025 Apr 28.\u003c/li\u003e\n \u003cli\u003eRojas-Rojas EA, Cinencio-Ch\u0026aacute;vez WR, Laniado-Labor\u0026iacute;n R (2023).\u0026nbsp;Delayed diagnosis of tuberculosis in a patient with coccidioidomycosis. Neumol Cir Torax 82(4):253-5.\u003c/li\u003e\n \u003cli\u003eCohen IM, Galgiani JN, Ogden DA (1981). Simultaneous tuberculosis and Coccidioidomycosis in end stage renal disease. Sabouraudia. 1981 19(1):13-6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Disseminated coccidioidomycosis, valley fever, tuberculosis, anti-TB treatment, Coccidioides posadasii, Mycobacterium tuberculosis, amphotericin B deoxycholate drug combination, antifungal treatment, abscess, coinfection pathogenesis","lastPublishedDoi":"10.21203/rs.3.rs-7964133/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7964133/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: \u0026nbsp;\u003cem\u003eMycobacterium\u003c/em\u003eand \u003cem\u003eCoccidioides\u003c/em\u003e are pathogenic microorganisms that can provoke progressive pulmonary or disseminated granulomatous diseases in humans. Tuberculosis (TB) and coccidioidomycosis have similar clinical and radiological presentations but require different treatments. Coinfection with TB and Coccidioides is exceptionally rare. Diagnosis may be missed even in endemic areas.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e: We present the case of a 34-year-old immunocompetent man with no previous history of TB exposure. Initially, microbiological and molecular tests were positive for Mycobacterium tuberculosis, which showed resistance to rifampicin, and he was discharged with TB treatment. However, after 27 days, he returned with abscesses on his head, left knee, shoulder, and left forefinger. Direct examination of the lesions with KOH and Grocott stain then revealed multiple endospore-containing spherules, confirming coccidioidomycosis. The fungus was further genotyped as \u003cem\u003eCoccidioides posadasii\u003c/em\u003e using 621 and GAC microsatellites. Treatment with antimycotic drugs (fluconazole and amphotericin B) led to improvement of the patient's chest X-ray and lesions after several weeks.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Though coinfection by \u003cem\u003eCoccidioides \u003c/em\u003eand\u003cem\u003e Mycobacterium \u003c/em\u003eis extremely rare, it can occur in immunocompetent patients exposed in endemic regions like northern Mexico. Treatment of tuberculosis with antimicrobials may mask or complicate the coccidioidomycosis diagnosis. Early diagnosis and intervention with antifungals such as amphotericin B and fluconazole can significantly improve clinical outcomes.\u003c/p\u003e","manuscriptTitle":"A case study of disseminated coccidioidomycosis following anti-TB treatment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-08 15:25:39","doi":"10.21203/rs.3.rs-7964133/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"613dcc50-3c20-49c6-877e-0c7850f91b60","owner":[],"postedDate":"November 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-08T15:25:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-08 15:25:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7964133","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7964133","identity":"rs-7964133","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}