Carolina Talhari

Randomized Controlled Clinical Trial to Access Efficacy and Safety of Miltefosine in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania (Viannia) guyanensis in Manaus, Brazil

Miltefosine has been used in the treatment of several new world cutaneous leishmaniasis (CL) species with variable efficacy. Our study is the first evidence on its clinical efficacy in Leishmania (Viannia) guyanensis. In this phase II/III randomized clinical trial, 90 CL patients were randomly allocated (2:1) to oral miltefosine (2.5 mg/kg/day/28 days) (N = 60) or parenteral antimony (15-20 mg/Sb/kg/day/20 days) (N = 30) according to age groups: 2-12 y/o and 13-65 y/o. Patients were human immunodeficiency virus (HIV) noninfected parasitological proven CL without previous treatment. Definitive cure was accessed at 6 months follow-up visit. No severe adverse events occurred. Vomiting was the most frequent adverse event (48.3%) followed by nausea (8.6%) and diarrhea (6.7%). Cure rates were 71.4% (95% confidence interval [CI] = 57.8-82.7) and 53.6% (95% CI = 33.9-72.5) (P = 0.05) for miltefosine and antimonial, respectively. There were no differences in cure rates between age groups within the same treatment arms. Miltefosine was safe and relatively well tolerated and cure rate was higher than antimony.

Leprosy and HIV Coinfection: A Clinical, Pathological, Immunological, and Therapeutic Study of a Cohort from a Brazilian Referral Center for Infectious Diseases

BACKGROUND Although awareness of the relevance of leprosy and human immunodeficiency virus (HIV) coinfection is increasing worldwide, several aspects of this co-occurrence are not fully understood. METHODS We describe clinical, pathological, immunological, and therapeutic long-term follow-up of a cohort of 25 individuals with leprosy and HIV infection from Manaus, Amazonas. RESULTS Careful description of our cohort indicates a higher prevalence of leprosy in an HIV-positive population than that in the general population. We also observed upgrading shifting of leprosy clinical forms after initiation of highly active antiretroviral therapy and multidrug therapy and an impact of HIV infection on leprosy granuloma formation, among other features. CONCLUSION Taken together, these new insights allow the proposition of a classification system that includes (1) leprosy and HIV true coinfection, (2) opportunistic leprosy disease, and (3) leprosy related to highly active antiretroviral therapy.

Tegumentary Leishmaniasis as the Cause of Immune Reconstitution Inflammatory Syndrome in a Patient Co-infected with Human Immunodeficiency Virus and Leishmania guyanensis

We report a case of immune reconstitution inflammatory syndrome (IRIS) in a 32-year-old man infected with human immunodeficiency virus and Leishmania guyanensis. Three months after initiation of highly active anti-retroviral therapy (HAART), the patient had disseminated cutaneous leishmaniasis and started anti-leishmanial therapy. The patients leishmaniasis manifestations during HAART ranged form an anergic response (46 CD4+ T cells/microL) to a disseminated cutaneous leishmaniasis (112 CD4+ T cells/microL). Eight weeks later (168 CD4+ T cells/microL, skin biopsy specimens showed inflammatory infiltrates with no detectable amastigotes. The patient then became comatose. Prednisone therapy (60 mg/day) was initiated with a significant improvement within 48 hours. Three months later (CD4+ T cell count = 184 cell/microL), localized, classic, cutaneous leishmaniasis developed in the patient and anti-leishmanial treatment was re-introduced. On that occasion, frequency of T regulatory cells was 1.82% of all CD4+ cells. Our data suggest a pivotal role for CD4+ T cells in the onset of IRIS and lesion ulceration and their association with a low frequency of T regulatory cells.

Successful treatment of linear IgA disease with mycophenolate mofetil as a corticosteroid sparing agent

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Subcutaneous phaeohyphomycosis in immunocompetent patients: two new cases caused by Exophiala jeanselmei and Cladophialophora carrionii.

Phaeohyphomycosis is a distinct mycotic infection of the skin or internal organs caused by darkly pigmented (dematiaceous) fungi, which are widely distributed in the environment. Phaeohyphomycosis is most frequently an opportunistic infection in immunosuppressed patients (HIV, corticotherapy, transplant patients) or is frequently associated with chronic diseases and diabetes. The spectrum of the disease is broad and includes superficial infections, onychomycosis, subcutaneous infections, keratitis, allergic disease, pneumonia, brain abscesses and disseminated disease. Rarely, immunocompetent patients may be affected. We describe two new cases of subcutaneous phaeohyphomycosis in immunocompetent patients: in the first patient, the causative agent was Exophiala jeanselmei, a common cause of phaeohyphomycosis; and in the second, Cladophialophora carrionii, which could be identified by culture. Cladophialophora carrionii is mainly the aetiological agent of chromoblastomycosis and only rarely the cause of phaeohyphomycosis. The first patient was treated with surgical excision and oral itraconazole, and the second patient responded to oral itraconazole only. Lesions improved in both patients and no recurrence was observed at follow‐up visits.

Leprosy and HIV coinfection: a critical approach

An increase in leprosy among HIV patients, similar to that observed in patients with TB, was expected approximately 20 years ago. Studies conducted in the 1990s together with those reported recently seemed to indicate that a coinfection with HIV did not alter the incidence and the clinical spectrum of leprosy and that each disease progressed as a single infection. By contrast, in countries with a high seroprevalence of HIV, TB was noted to increase. Explanations may be provided by the differences in the incubation time, the biology and toxicity of Mycobacterium leprae and Mycobacterium tuberculosis. After the introduction of HAART the leprosy–HIV coinfection manifested itself as an immune reconstitution inflammatory syndrome (IRIS), typically as paucibacillary leprosy with type 1 leprosy reaction. The incidence of leprosy in HIV-infected patients has never been properly investigated. IRIS-leprosy is probably underestimated and recent data showed that the incidence of leprosy in HIV patients under HAART was higher than previously thought.

Borrelia burgdorferi "sensu lato" in Brazil: occurrence confirmed by immunohistochemistry and focus floating microscopy.

In the present study, we report the occurrence of Lymes borreliosis in patients from the Brazilian Amazon Region. Borreliosis was investigated by immunohistochemistry and focus floating microscopy for Borrelia burgdorferi in skin biopsy samples from 22 patients with both clinical and histopathology evidences compatible with Erythema Migrans. Spirochetes were detected by specific immunohistochemistry and focus floating microscopy for B. burgdorferi in samples from five patients. Clinical cure of the cutaneous lesions was observed in all the patients after treatment with doxycycline regimen as proposed by the Center Disease Control guidelines. A limitation of our study was the fact that we were not able to isolate and culture these organisms. These are the first known Brazilian cases of borreliosis to have Focus Floating Microscopy confirmation.

Oral exfoliative cytology as a rapid diagnostic tool for paracoccidioidomycosis

Paracoccidioidomycosis is a common deep mycosis in South America. It is caused by the dimorphic fungus Paracoccidioides brasiliensis. We report a case of a 47‐year‐old Brazilian man with oral lesions due to paracoccidioidomycosis, which was diagnosed by exfoliative cytology without any special staining. We highlight this diagnostic tool as a simple, low‐cost, painless, non‐invasive and fast method for the diagnosis of paracoccidioidomycosis.

Presence of Borrelia burgdorferi“Sensu Lato” in patients with morphea from the Amazonic region in Brazil

Background  In the present study, Borrelia spirochetes were found in four (26,6%) out of 15 patients with Atrophoderma of Pasini and Pierini (IAPP) and lichen sclerosis et atrophicans (LSA) from the Brazilian Amazon Region.

Combining diagnostic procedures for the management of leishmaniasis in areas with high prevalence of Leishmania guyanensis

BACKGROUND The Amazon region corresponds to approximately 40% of the cases of leishmaniasis in Brazil. We report a prospective study with 180 patients conducted in a health care unit that diagnoses 10% of the cases of leishmaniasis in the Brazilian Amazon. The study addresses how a combination of procedures improves diagnosis in areas with high prevalence of Leishmania guyanensis. OBJECTIVES to evaluate diagnostic methods in areas with high prevalence of Leishmania guyanensis. METHODS All subjects were amastigote-positive by direct microscopic examination of lesion scarifications. We conducted skin biopsy and histopathology, polymerase chain reaction and parasite cultivation. RESULTS Polymerase chain reaction detected almost ninety percent of infections when two amplification protocols were used (mini-exon and HSP-70). HSP-70 specific polymerase chain reaction matched the sensitivity of parasite cultivation plus histopathology. CONCLUSION The best combination was polymerase chain reaction plus histopathology, which increased diagnostic sensitivity to 94%. Species discrimination by polymerase chain reaction disclosed prevalence of human infections with Leishmania guyanensis of 94% and with Leishmania braziliensis of 6% for this region.