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Revista Do Instituto de Medicina... 2022Paracoccidioidomycosis (PCM) may present as an acute/subacute clinical form, characterized by a progressive disease arising from the airborne initial infection, or, most...
Paracoccidioidomycosis (PCM) may present as an acute/subacute clinical form, characterized by a progressive disease arising from the airborne initial infection, or, most often, as an asymptomatic or subclinical infection that may manifest later during an individual's life, the chronic form. Epidemiological studies show the existence of a strong association between smoking and the development of the chronic form. Current evidence demonstrates that cigarette smoke (CS) has immunosuppressive properties that could be implicated in the increasing susceptibility to the chronic form of PCM. To address this issue, we developed a murine model of a non-progressive pulmonary form of PCM that was exposed to CS at a magnitude that mimicked a moderate smoker. The chronic CS exposure started after 2 weeks and lasted up until 20 weeks post-infection, with the aim of mimicking human natural history, since it is estimated that individuals from endemic areas are infected early in life. The control group consisted of infected but not CS-exposed mice. We assessed the lung fungal burden (colony forming units [CFU]) and the area affected by the granulomatous inflammatory response, fungal dissemination to spleen and liver, and, by immunohistochemistry, the presence of CD4 and CD8 lymphocytes, CD68 and MAC-2 macrophages, and IFN-γ, IL-10 and TNF expressing cells within the granulomatous response. We detected a CS effect as early as 2 weeks after exposure (four weeks post-infection) when the lung CFU of exposed animals was significantly higher than in their non-exposed counterparts. At 12 weeks, the CS-exposed animals presented a more severe disease, as witnessed by the persistent higher lung fungal load (although it did not reach statistical significance [ p = 0.054]), greater dissemination to other organs, greater affected area of the lung, decreased IFN-γ/IL-10 ratio, and higher TNF expression within the granulomas, compared with CS-non-exposed mice. The number of CD4 and CD8 lymphocytes infiltrating the granulomas was similar between both mice groups, but there was a decrease in the number of MAC-2+ macrophages. No difference was noted in the CD68+ macrophage number. However, the follow-up in week 20 showed that the immunological effects of exposure to CS ceased, with both CS and NCS mice showing the same infectious features, i.e., a trend for resolution of the infection. In conclusion, we show that chronic CS-exposure alters the course of the disease in an experimental model of subclinical pulmonary PCM, confirming the epidemiological link between CS-exposure and the chronic form of PCM. However, we also show that this effect is transitory, being detected between 4- and 12-weeks post-infection but not thereafter. The possible immune mechanisms that mediate this effect and the reasons for its transitory effect are discussed.
Topics: Humans; Mice; Animals; Paracoccidioidomycosis; Interleukin-10; Disease Models, Animal; Cigarette Smoking; Disease Progression; Granuloma; Mice, Inbred C57BL
PubMed: 36383893
DOI: 10.1590/S1678-9946202264071 -
Revista Da Sociedade Brasileira de... 2021
Topics: Humans; Paracoccidioidomycosis
PubMed: 33681928
DOI: 10.1590/0037-8682-0620-2020 -
Biomedica : Revista Del Instituto... Aug 2023Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. Climate change and host migration emphasize the need to optimize this infection diagnosis.
INTRODUCTION
Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. Climate change and host migration emphasize the need to optimize this infection diagnosis.
OBJECTIVE
To evaluate the implementation of Paracoccidioides spp. DNA detection in the mycological diagnosis of patients with suspected paracoccidioidomycosis.
MATERIALS AND METHODS
It is a retrospective study with laboratory data from patients with clinical suspicion of paracoccidioidomycosis, who consulted a university hospital from a non-endemic area.
RESULTS
We analyzed the laboratory results of samples from 19 patients with suspected paracoccidioidomycosis. Seventeen out of 19 patients were born in or had visited an endemic area in Latin America. Fourteen adult male patients were confirmed to have paracoccidioidomycosis by conventional diagnosis: the direct examination was positive in 12 samples while fungal growth was found only in 4. Anti-Paracoccidioides spp. antibodies were detected in 10 patients, 8 of them with proven paracoccidioidomycosis. Nested PCR for Paracoccidioides spp. detection was performed on clinical samples from 14 patients, and positive results were obtained for 9 out of 10 patients with the conventional diagnosis of paracoccidioidomycosis.
CONCLUSIONS
The incorporation of molecular techniques to detect Paracoccidioides spp. DNA complements the conventional diagnosis of paracoccidioidomycosis. This tool allows the prescription of antifungal treatment in those cases where the fungus is not observed in the clinical samples.
Topics: Hospitals; Polymerase Chain Reaction; Tolnaftate
PubMed: 37721907
DOI: 10.7705/biomedica.6888 -
PLoS Neglected Tropical Diseases Aug 2020Genotyping of the genus Paracoccidioides showed its diversity and geographical distribution. Four species constituting the Paracoccidioides brasiliensis complex and...
Comparison of clinico-epidemiological and radiological features in paracoccidioidomycosis patients regarding serological classification using antigens from Paracoccidioides brasiliensis complex and Paracoccidioides lutzii.
Genotyping of the genus Paracoccidioides showed its diversity and geographical distribution. Four species constituting the Paracoccidioides brasiliensis complex and Paracoccidioides lutzii are etiological agents of paracoccidioidomycosis (PCM). However, there are no studies comparing the clinical and epidemiological aspects between PCM caused by the P. brasiliensis complex and by P. lutzii. Demographic and clinical data from 81 patients with PCM-confirmed by mycological and/or histopathological examination-from Mato Grosso do Sul state (Brazil) were studied. All patients underwent serology by immunodiffusion with antigens obtained from the P. brasiliensis complex (ExoPb and gp43) and Cell Free Antigens obtained from P.lutzii (CFAPl).The cases were classified regarding their serological profile into three groups: G1: PCM patients seropositive to ExoPb and/or gp43 and seronegative to CFAPl (n = 51), assumed to have PCM caused by P. brasiliensis complex; G2: PCM patients seronegative to gp43 and seropositive to CFAPl (n = 16), with PCM caused by P. lutzii; and G3: PCM patients seropositive to ExoPb or gp43 and seropositive to CFAPl (n = 14), with undetermined serological profile, was excluded from the analyses. The Fisher's exact test or the Mann-Whitney U test, and cluster analysis according to Ward's method and Euclidean distance were used to analyze the results. Patients with serological profile suggestive of P. lutzii lived predominantly in municipalities in the Central and Southern regions of the state, while those with serological profile indicative of the P. brasiliensis complex were distributed throughout the state. No differences were found between the two groups regarding gender, age, schooling, rural work, clinical form, severity, organs involved, intensity of pulmonary involvement, degree of anemia, erythrocyte sedimentation rate values, and therapeutic response. PCM patients with serological profile suggestive of P. lutzii and PCM patients with serological profile indicative of P. brasiliensis complex showed the same clinical and radiological presentations.
Topics: Adolescent; Adult; Aged; Antigens, Fungal; Brazil; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Paracoccidioides; Paracoccidioidomycosis; Serologic Tests; Young Adult
PubMed: 32841237
DOI: 10.1371/journal.pntd.0008485 -
PloS One 2018Mucocutaneous leishmaniasis and paracoccidioidomycosis are infectious diseases with similar epidemiological and clinical aspects. Cases of both diseases may manifest...
Mucocutaneous leishmaniasis and paracoccidioidomycosis are infectious diseases with similar epidemiological and clinical aspects. Cases of both diseases may manifest similar lesions in the mucosa. Therefore, the determination of distinguishing characteristics for the purpose of differential diagnosis is critical for better management of the diseases. The present study evaluated factors that assist in the differentiation of mucosal lesions between these diseases. This cross-sectional study included data from medical records of 122 cases of mucocutaneous leishmaniasis and 83 cases of paracoccidioidomycosis attended at the university hospital Cassiano Antonio Moraes, located in Vitória, Espírito Santo State, Brazil. Comparison between the diseases included the following variables: sex, age, time of disease evolution, location of the lesion and symptoms. Adults and males were affected by both diseases at higher rates. Lesions in the nasal region (95.1%; p-value = 0.000) and the pharynx (20.5%; p-value = 0.009) and nasal obstruction (34.4%; p-value = 0.000) were associated with leishmaniasis. Paracoccidioidomycosis was associated with lesions in the oral region (90.4%; p-value = 0.000), oral pain (16.9%; p-value = 0.000), and hoarseness (14.5%; p-value = 0.008). In leishmaniasis, lesions in oral regions were not associated with oral pain and were frequently located close to the nasal area. The manifestations cited above could improve the differential diagnosis of leishmaniasis and paracoccidioidomycosis, and thereby potentially aid in the choice of appropriate confirmatory diagnostic testing.
Topics: Adult; Age Factors; Aged; Brazil; Cross-Sectional Studies; Diagnosis, Differential; Female; Humans; Leishmaniasis, Mucocutaneous; Male; Middle Aged; Mouth Mucosa; Nasal Mucosa; Paracoccidioidomycosis; Pharynx; Sex Factors; Tongue
PubMed: 30475920
DOI: 10.1371/journal.pone.0208208 -
The American Journal of Case Reports Oct 2017BACKGROUND Paracoccidioidomycosis is an endemic mycosis in Central and South America caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. Despite its...
BACKGROUND Paracoccidioidomycosis is an endemic mycosis in Central and South America caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. Despite its self-limited course and usually asymptomatic infection, some patients may present with a systemic illness mimicking multiple conditions and thus question the general state of their immune system. CASE REPORT A 28-year-old male presented to the hospital with fever, dry cough, and non-pruritic rash with no characteristic distribution for the past 10 days. Past medical history revealed that the patient had worked as a farmer three years ago, had abused cocaine paste over the same period, and also had in the last month presented to the hospital for acute appendicitis. Initial laboratory tests revealed hypereosinophilia greater than 10,000 eosinophils/mL. Infection of P. brasiliensis was confirmed by lymph node, skin, and colonoscopy biopsies. After treatment with itraconazole, the patient's eosinophil count returned to normal and his symptoms resolved. CONCLUSIONS Paracoccidioidomycosis may present as a systemic illness with only marked eosinophilia on initial diagnostic tests. Furthermore, in our patient's case, the high degree of eosinophilia may have contributed towards the patient's appendicitis in the weeks preceding the subacute infection. It is possible that the patient's history of working at a farm and abusing cocaine paste may have contributed to the initial colonization by the fungus.
Topics: Adult; Eosinophilia; Humans; Male; Paracoccidioidomycosis
PubMed: 29042530
DOI: 10.12659/ajcr.904520 -
American Journal of Ophthalmology Case... Sep 2021To report a case of aggressive chorioretinal paracoccidioidomycosis requiring treatment with systemic antifungal agents, frequent intravitreal voriconazole injections,...
PURPOSE
To report a case of aggressive chorioretinal paracoccidioidomycosis requiring treatment with systemic antifungal agents, frequent intravitreal voriconazole injections, and surgical excision.
OBSERVATIONS
A Brazilian man in his mid-30s with a history of chronic, biopsy-proven cutaneous paracoccidioidomycosis, chronic sinusitis, and perichondritis secondary to paracoccidioidomycosis presented with profound vision loss. He was found to have significant vitreous inflammation and a large chorioretinal lesion in the posterior pole concerning for ocular involvement. He was treated initially with combined topical and systemic steroids as well as systemic antifungals and antibiotics, then with serial intravitreal voriconazole injections resulting in a significant reduction of intraocular inflammation and subretinal fluid. The residual tractional retinal detachment from the chorioretinal lesion was addressed surgically by pars plana vitrectomy.
CONCLUSION AND IMPORTANCE
Intravitreal voriconazole can be an effective adjuvant treatment for the vitreous inflammation and subretinal fluid associated with chorioretinal paracoccidioidomycosis. Surgical intervention may be indicated in cases complicated by tractional retinal detachment.
PubMed: 34430756
DOI: 10.1016/j.ajoc.2021.101187 -
Medical Mycology Case Reports Jun 2018Paracoccidioidomycosis (PCM) is the most widespread endemic mycosis in LatinAmerica. If PCM is not diagnosed and treated early and adequately, the endemic fungal...
Paracoccidioidomycosis (PCM) is the most widespread endemic mycosis in LatinAmerica. If PCM is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. We report a case of PCM with duodenal and cutaneous involvement simulating cholangitis that was initially misdiagnosed as a lymphoproliferative disease. Clinicians should consider acute paracoccidioidomycosis in the differential diagnosis of jaundice and/or signs/symptoms of cholangitis developing in young patients from paracoccidioidomycosis endemic regions.
PubMed: 30148057
DOI: 10.1016/j.mmcr.2018.01.005 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 μg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/μl compared with 24.26 when CD4 count <50 cells/μl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.
Topics: Talaromyces; Humans; Paracoccidioides; Antifungal Agents; Coccidioides; World Health Organization; Mycoses; Paracoccidioidomycosis; Coccidioidomycosis; Microbial Sensitivity Tests
PubMed: 38935909
DOI: 10.1093/mmy/myad133 -
Acta Tropica Jun 2020Fungal infections have been increasing in recent decades, mainly affecting immunocompromised individuals, although certain mycoses, such as paracoccidioidomycosis (PCM),... (Review)
Review
Fungal infections have been increasing in recent decades, mainly affecting immunocompromised individuals, although certain mycoses, such as paracoccidioidomycosis (PCM), infect immunologically competent individuals. The major problems observed regarding fungal diseases are inadequate diagnosis, prolonged treatment time, the reduced number of drugs available for treatment, in addition to the fact that there are no vaccines for clinical use. Drug combination in order to immunomodulate the immune response is a new strategy used for the treatment of mycoses, since it is difficult to develop new antifungal drugs. The aim of this study is to present and analyze strategies recently suggested for the treatment of fungi of medical interest, in particular for PCM, such as the utilization of combinations of protein fractions or dead microorganisms, as vaccinal antigens, and cellular immunotherapy. We will also propose new therapeutic alternatives, such as lipids, vitamins, synthetic or natural products as well as the use of low intensity LASER therapy (LLLT) to modulate the immune response of the host, enhancing the efficiency of the existing treatments of mycoses of medical interest and in particular of PCM.
Topics: Antifungal Agents; Humans; Immunomodulation; Immunotherapy; Paracoccidioidomycosis
PubMed: 32135141
DOI: 10.1016/j.actatropica.2020.105412