Deep fungal infections in tropical countries

Rivitti, Evandro A.; Aoki, Valéria

doi:10.1016/s0738-081x(99)00010-3

Cited by 64 publications

(62 citation statements)

References 48 publications

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“…Therefore, when systemic administration of drugs is required for deep human mycoses, few compounds are sufficiently selective (12). Compounds currently used in the control of infection caused by P. brasiliensis include amphotericin B, trimethoprimsulfamethoxazole, and azole derivatives (26). Unfortunately, amphotericin B has been associated with substantial toxicity, while trimethoprim-sulfamethoxazole has been associated with relapses.…”

Section: Paracoccidioidomycosis Caused By the Dimorphic Fungusmentioning

confidence: 99%

In Vitro Comparison of Activities of Terbinafine and Itraconazole against Paracoccidioides brasiliensis

et al. 2002

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In vitro, terbinafine is highly active against a broad spectrum of pathogenic fungi. We evaluated the activities of terbinafine and itraconazole against 31 isolates of Paracoccidioides brasiliensis. The tests were conducted by using a broth macrodilution procedure. MICs, in micrograms per milliliter, were as follows: terbinafine, 0.015 to 1.0 (geometric mean, 0.1188); itraconazole, 0.007 to 0.5 (geometric mean, 0.03165). The usual therapy for paracoccidioidomycosis is sulfonamides, amphotericin B, and azole derivatives (ketoconazole, itraconazole, and fluconazole). In comparison to amphotericin B, azole derivatives allow shorter treatment courses, can be administered orally, and are equally effective. Itraconazole has as high efficacy as ketoconazole, but with superior tolerance. It is the current drug of choice for treatment of paracoccidioidomycosis. The data obtained in this study indicate that terbinafine is active against P. brasiliensis in vitro and suggest that this allylamine can be considered a new option as drug therapy for paracoccidioidomycosis.Paracoccidioidomycosis, caused by the dimorphic fungus Paracoccidioides brasiliensis, is a systemic human mycosis geographically confined to Latin America (1,25,28). In vitro tests of the susceptibility of P. brasiliensis to antimycotic drugs have been scarce, and the results have not always been consistent; the discrepancies are attributed to the diversity of techniques employed in such studies (7,8,10,11,22,28).Organisms belonging to the kingdom Fungi share eukaryotic characteristics with their human host cells, implying similarities in biochemistry and physiology that limit therapeutics. Therefore, when systemic administration of drugs is required for deep human mycoses, few compounds are sufficiently selective (12). Compounds currently used in the control of infection caused by P. brasiliensis include amphotericin B, trimethoprimsulfamethoxazole, and azole derivatives (26). Unfortunately, amphotericin B has been associated with substantial toxicity, while trimethoprim-sulfamethoxazole has been associated with relapses. Thus, in many clinical situations, the azole derivatives present the best therapeutic option for control of paracoccidioidomycosis (17, 18).Owing to the fact that itraconazole, among the azoles, permits shorter treatment courses and has been shown to be more effective, we decided to compare this drug with the antifungal agent terbinafine, which operates by interfering with the ergosterol biosynthetic pathway and has shown MICs similar to those of itraconazole for filamentous fungi in in vitro studies (10,15). Thus, we aim to determine whether terbinafine might have a role in the management of infections caused by P. brasiliensis. MATERIALS AND METHODSFungal strains and culture conditions. Thirty-one isolates of the P. brasiliensis yeast form, including clinical, environmental, and animal isolates, were examined in this study. Samples consisted of 28 strains isolated from humans, 1 from penguin feces, 1 from dog food, and 1 from an armadillo....

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Section: Paracoccidioidomycosis Caused By the Dimorphic Fungusmentioning

confidence: 99%

In Vitro Comparison of Activities of Terbinafine and Itraconazole against Paracoccidioides brasiliensis

et al. 2002

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“…However, this disease is commonly seen in tropical and subtropical regions [1]. It is caused by traumatic inoculation of the dimorphic fungus Sporothrix schenckii, which is an ubiquitous environmental saprophyte that can be isolated from soil and plant debris [2].…”

Section: Introductionmentioning

confidence: 99%

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

et al. 2008

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Cell-mediated and innate immunity are considered the most important mechanisms of host defense against fungus infections. However, recent studies demonstrated that specific antibodies show different degrees of protection against mycosis. In a previous study, antigens secreted by Sporothrix schenckii induced a specific humoral response in infected animals, mainly against the 70-kDa molecule, indicating a possible participation of antibodies to this antigen in infection control. In the present study, an IgG1 mAb was produced against a 70-kDa glycoprotein of S. schenckii in order to better understand the effect of passive immunization of mice infected with S. schenckii. Results showed a significant reduction in the number of CFU in organs of mice when the mAb was injected before and during S. schenckii infection. Similar results were observed when T-cell-deficient mice were used. Moreover, in a second schedule treatment, the mAb was injected after infection was established, and again we observed a significant reduction in CFU associated with an increase of IFN-cproduction. Also, the 70-kDa antigen is shown to be a putative adhesin present on the surface of this fungus. In conclusion, we report for the first time the protective effect of a specific antibody against S. schenckii.Key words: Adhesins . Mab . Passive immunization . Sporothrix schenckii . Sporotrichosis IntroductionSporotrichosis is a chronic subcutaneous mycosis that occurs worldwide. However, this disease is commonly seen in tropical and subtropical regions [1]. It is caused by traumatic inoculation of the dimorphic fungus Sporothrix schenckii, which is an ubiquitous environmental saprophyte that can be isolated from soil and plant debris [2]. In the past, infections were limited to the cutaneous forms of the disease.Recently, occurrences of more severe clinical forms of this mycosis were described, especially among immunocompromised individuals [3,4].The immunological mechanisms involved in prevention and control of sporotrichosis suggest that cell-mediated immunity plays an important role in protecting The host against S. schenckii [5]. In experimental infections, athymic nude mice are more susceptible to sporotrichosis, and acquired immunity against S. schenckii is mainly mediated by T-cell-activated macrophages [6,7].In contrast, the role of the humoral immune response in protection against this fungus has not been studied in detail. In a previous study, we showed that antigens secreted by S. 3080induce a specific humoral response in infected animals, mainly against the 70-kDa molecule, indicating a possible participation of specific antibodies to this molecule in infection control [8].Cell-mediated and innate immunity are considered the most important mechanisms of host defense against fungus infections. However, recent studies demonstrated that antibodies with defined specificity show different degrees of protection against mycosis [9]. Administration of mAb-mediated protection against Paracoccidioides brasiliensis and Candida albicans and modif...

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“…The organism occurs worldwide and is most commonly found in soil, sphagnum moss, and decaying vegetation. Although sporotrichosis is most often reported from Mexico and Central and South America, it is also common in Asia and more widespread in temperate and tropical zones (9,16). Most often, the infection occurs following minor traumatic events leading to the implantation of the fungus onto the skin.…”

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confidence: 99%

Detection of Sporothrix schenckii in Clinical Samples by a Nested PCR Assay

Hu¹,

Chung²,

Hung

et al. 2003

J Clin Microbiol

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Cutaneous sporotrichosis is a chronic granulomatous fungal infection caused by Sporothrix schenckii with worldwide distribution. Its traditional diagnosis is time-consuming and difficult to differentiate from that of a clinical sporotrichoid lesion caused by various pathogens. In this study, a nested PCR assay for the detection of S. schenckii was evaluated by using a sequence of 18S rRNA gene as a target. For the examination of specificity and sensitivity, five clinical isolates with 1 ATCC 10213 strain of S. schenckii, 10 strains of clinical common fungi, 3 strains of Mycobacterium spp., Staphylococcus aureus, and normal human skin tissue were used. The expected fragment was amplified from six S. schenckii isolates in the first round and nested PCR but not from other microorganisms and human DNA. Their sequences were 100% identical to the S. schenckii 18S rRNA gene sequence deposited in GenBank. A detection limit of 40 fg of S. schenckii DNA extract was determined with ethidium bromide staining. Serial dilution studies demonstrated that the nested PCR could detect a DNA amount of 1 CFU of S. schenckii in tissue samples. We further investigated the nested PCR assay for the detection of S. schenckii from the tail tissues of 5 experimentally infected mice and from the clinical biopsy specimens of 12 patients with sporotrichosis confirmed by culture or histochemical staining. The nested PCR assay was positive in all 5 infected mice and in 11 of the 12 clinical specimens. The high sensitivity and specificity of this nested PCR indicate that the assay can provide rapid diagnosis with sufficient accuracy to be clinically useful for patients with sporotrichosis.

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Deep fungal infections in tropical countries

Cited by 64 publications

References 48 publications

In Vitro Comparison of Activities of Terbinafine and Itraconazole against Paracoccidioides brasiliensis

In Vitro Comparison of Activities of Terbinafine and Itraconazole against Paracoccidioides brasiliensis

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

Detection of Sporothrix schenckii in Clinical Samples by a Nested PCR Assay

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