Fundamentals of paracoccidioidomycosis treatment

Abstract

Paracoccidioidomycosis (PCM) is the most important mycosis in Latin America. The etiological agent is the fungus, Paracoccidioides brasiliensis. Approximately 1 million people are infected with the fungus, 10% of whom will show symptoms of the disease. However, clinical and laboratorial studies addressing the diagnosis for this disease are both scarce and diverse in terms of definition. Nevertheless, two main advances were included in the portfolio of available diagnostic methods for paracoccidioidomycosis during the last decades: the detection of antibodies against P. brasiliensis antigens by serological methods, and the detection of the fungi DNA in peripheral blood and fragments of lesions using the polymerase chain reaction (PCR) assay and species-specific primers. Normally, the treatment of PCM is quite prolonged because of the immunosuppressed profile of the patients and the ability of P. brasiliensis to survive in the tissues even after long-term treatment. Case reports indicate that azoles and sulfa compounds can produce positive results in less severe cases of PCM. However, for acute cases of the disease in immunocompromised patients or in cases of neuroparacoccidioidomycosis, there is no standard treatment. Thus, there is a need to establish a standard treatment protocol within the context of the patient clinical profile. Moreover, drug availability to public institutions is an important issue, since new drugs, e.g., second-generation azoles, the echinocandines and immunomodulatory drugs, are not yet available in public hospitals and clinics. Drug Dev Res 72:528-537, 2011.

Paracoccidioidomycosis

“…In Brazil, the combination sulfamethoxazole-trimethoprim has been preferentially used for treating PCM patients with ensuing healing of most lesions (Table 19.2). In less severe forms of the disease, the latter should be administered for a period of 2 years, resulting in high-dropout rates during treatment (Table 19.2) [51,89,90]. Tolerability is good, with myelotoxicity (leukopenia) being the main side effect, one that can be monitored and controlled by folinic acid administration without modification of the therapeutic regimen [1,89].…”

“…Patients may need to be hospitalized for side effects caused by the drugs [1,89,90]. The patient should remain in treatment and under follow-up management until achieving apparent resolution, with assessment based on clinical, radiological, and serological parameters.…”

“…They include the sulfonamides, the polyene amphotericin B (AmB) and its lipid formulations, and certain azoles (Table 19.2) [51,89]. Normally, the treatment of PCM is quite prolonged because of the patients' low immunity profile plus P. brasiliensis ability to survive in the tissues even after long-term treatment.…”

“…In less severe forms of the disease, the latter should be administered for a period of 2 years, resulting in high-dropout rates during treatment (Table 19.2) [51,89,90]. Tolerability is good, with myelotoxicity (leukopenia) being the main side effect, one that can be monitored and controlled by folinic acid administration without modification of the therapeutic regimen [1,89]. Other side effects seen with this association include rash, gastritis, and interstitial nephritis; all reversible with interruption of treatment.…”

“…Normally, the treatment of PCM is quite prolonged because of the patients' low immunity profile plus P. brasiliensis ability to survive in the tissues even after long-term treatment. The treatment option must consider the severity of disease; establishment of standard treatment protocols within the context of the patient clinical profile is a requisite [1,6,51,[89][90][91]. First-and second-generation azoles, such as ketoconazole, itraconazole and voriconazole, have emerged as therapeutic options for the control of the disease's moderate forms in shorter periods of time [91,92].…”