Some pathogens (e.g., Mycobacterium tuberculosis, Toxoplasma gondii, Leishmania spp) have been shown to persist in their host after clinical cure, establishing the risk of disease reactivation. We analyzed the conditions necessary for the long term maintenance of Leishmania major in genetically resistant C57BL/6 mice after spontaneous healing of their dermal lesions. Interleukin (IL)-10 was found to play an essential role in parasite persistence as sterile cure was achieved in IL-10–deficient and IL-4/IL-10 double-deficient mice. The requirement for IL-10 in establishing latency associated with natural infection was confirmed in IL-10–deficient mice challenged by bite of infected sand flies. The host-parasite equilibrium was maintained by CD4+ and CD8+ T cells which were each able to release IL-10 or interferon (IFN)-γ, and were found to accumulate in chronic sites of infection, including the skin and draining lymph node. A high frequency of the dermal CD4+ T cells released both IL-10 and IFN-γ. Wild-type mice treated transiently during the chronic phase with anti–IL-10 receptor antibodies achieved sterile cure, suggesting a novel therapeutic approach to eliminate latency, infection reservoirs, and the risk of reactivation disease.

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The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti–IL-10 Receptor Antibody for Sterile Cure

Sporotrichosis, which is caused by the dimorphic fungus Sporothrix schenckii, is currently distributed throughout the world, especially in tropical and subtropical zones. Infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Certain leisure and occupational activities, such as floriculture, agriculture, mining, and wood exploitation, are traditionally associated with the mycosis. Zoonotic transmission has been described in isolated cases or in small outbreaks. Since the end of the 1990s there has been an epidemic of sporotrichosis associated with transmission by cats in Rio de Janeiro, Brazil. More than 2,000 human cases and 3,000 animal cases have been reported. In humans, the lesions are usually restricted to the skin, subcutaneous cellular tissue, and adjacent lymphatic vessels. In cats, the disease can evolve with severe clinical manifestations and frequent systemic involvement. The gold standard for sporotrichosis diagnosis is culture. However, serological, histopathological, and molecular approaches have been recently adopted as auxiliary tools for the diagnosis of this mycotic infection. The first-choice treatment for both humans and cats is itraconazole.

https://www.arca.fiocruz.br/bitstream/icict/36974/2/ve_Barros_M%c3%b4nica_etal_INI_2011.pdf

Sporothrix schenckii and Sporotrichosis

Leishmania parasites are the etiological agents of the leishmaniases. The parasites are transmitted to mammals, including humans, by the bite of phlebotomine sand flies and occasionally, by sharing of needles, blood transfusion, and congenital transmission ([18][1]). In terms of global burden of

Molecular diagnosis of leishmaniasis: current status and future applications.

Tegumentary leishmaniasis, comprising the cutaneous and mucocutaneous forms, is caused by at least 13 dermotropic species of protozoa of the genus Leishmania, most of which are prevalent in the New World. Although diseases in the Old and New Worlds share similar characteristics, the ultimate manifestations and severity are quite different, with more severe forms associated with mucosal lesions observed in the New World. For the diagnosis and treatment of leishmaniasis, differences based on clinical features, usefulness/sensitivity of diagnostic methods and therapeutic responses are mainly emphasized. We present a critical review of the diagnostic methods, their contribution and the necessity for their improvement/development, particularly in molecular diagnosis aimed at detection and species identification, as well as serodiagnosis. In addition to a review of the drugs currently utilized, we describe differences in their effectiveness in Old and New World leishmaniasis. HIV/Leishmania coinfection is also presented in the context of diagnosis and treatment.

https://www.tandfonline.com/doi/pdf/10.1586/eri.10.19

Current diagnosis and treatment of cutaneous and mucocutaneous leishmaniasis

Vaccines against a variety of infectious diseases represent one of the great triumphs of medicine. The immune correlates of protection induced by most current vaccines seem to be mediated by long-lived humoral immune responses. By contrast, there are no currently available vaccines that are uniformly effective for diseases such as HIV, malaria and tuberculosis, in which the cellular immune response might be crucial in mediating protection. Here we examine the mechanisms by which long-lived cellular immune responses are generated and maintained in vivo. We then discuss current approaches for vaccination against diseases in which cellular immune responses are important for protection.

/pdf/vaccines-against-intracellular-infections-requiring-cellular-3v8o3fdned.pdf

Vaccines against intracellular infections requiring cellular immunity.

Leishmaniasis is an endemic disease in developing countries. The efficacy of therapy is usually evaluated through clinical parameters. To define the parasitologic cure, 20 patients were biopsied before and 1 month to 8 years after treatment. Paraffin-embedded tissue was used for DNA isolation. All patients had a positive polymerase chain reaction (PCR) result before therapy, except 1, for whom no histopathologic material was available. The causative agent was identified as belonging to the Leishmania (Viannia) subgenus by hybridization. Despite clinical healing and absence of reactivation or development of mucosal lesions, PCR was positive in scars of 16 patients (80%). The results suggest that parasites persist in the skin for many years despite treatment. Depending on specific pathogenetic features of the parasite and the immune status of the host, this phenomenon might result in mucosal lesions. Alternatively, it could have a role in the maintenance of immunologic memory in patients living in areas in which leishmaniasis is endemic.

Detection of Leishmania DNA by Polymerase Chain Reaction in Scars of Treated Human Patients

The efficacy of an antimony regimen at the dose of 20 mg/kg/day for a 3-4-week period is well established in the treatment of American cutaneous leishmaniasis. Several drug side effects, however, have been described and the search for more suitable regimens is advisable. In the present paper, the effect of a low dose (5 mg/kg/day for 30 days) of antimony was evaluated in 159 individuals from endemic regions of Rio de Janeiro State, Brazil, an area of Leishmania (V.) braziliensis transmission. Patients presented typical cutaneous lesions and parasites were demonstrated in all cases. One hundred forty-three patients were available for evaluation and of these, 120 (84%) were cured by the end of therapy. Twenty-three patients (16%) were considered treatment failures. Side effects were observed in only six patients (4%). Extensive follow-up (up to 10 years) disclosed no relapses or mucosal lesions. The results show that a low dose of antimony is less toxic, more appropriate, especially in children and elderly people, and has the same final result as that obtained with larger doses.

A Low-Dose Antimony Treatment in 159 Patients with American Cutaneous Leishmaniasis: Extensive Follow-up Studies (Up to 10 Years)

Treatment of American cutaneous leishmaniasis: a comparison between low dosage (5 mg/kg/day) and high dosage (20 mg/kg/day) antimony regimens.

1 Resumo Com o objetivo de estudar o comportamento biologico de cepas do T. cruzi e determinar a possivel relacao entre o biodema da cepa e as formas clinicas da doenca de Chagas, 14 cepas do protozoario isoladas de humanos, procedentes de Pains, Iguatama e Berilo, foram avaliadas. Para estudar o comportamento biologico das cepas, grupos de camundongos albinos suicos, machos, pesando entre 10-15 gramas foram infectados com 1x10 4 tripomastigotas sanguineos para avaliacao da infectividade , parasitemia, morfologia dos tripomastigotas sanguineos, virulencia e distribuicao do protozoario nos tecidos. Nove cepas apresentaram comportamento similar ao da cepa Sao Felipe do biodema II e cinco se caracterizaram como pertencentes ao biodema III. Nao foi possivel estabelecer uma relacao entre o biodema da cepa e gravidade da doenca nos pacientes. Palavras-chaves: Trypanosoma cruzi. Biodema. Comportamento biologico. Doenca de Chagas. Abstract In order to study the biological behavior of T. cruzi strains and to determine a putative association between their biodeme and the clinical forms of Chagas disease, 14 strains isolated from humans were evaluated. The individuals were from the municipalities of Pains, Iguatama and Berilo (Minas Gerais State). The biological behavior was evaluated in albino swiss mice, weighing 10 to 15 grams, which were infected with 1x10 4 blood tripomastigotes. The infectivity, parasitemia, tripomastigote morphology, virulence and the tissue distribution of the protozoan were analyzed. A behavior similar to biodeme II (Sao Felipe strain) was observed in 9 strains, while 5 stocks were characterized as belonging to biodeme III. It was not possible to establish a relationship between the biodeme strain and the severity of the disease in the patients.

Biodemas de cepas do Trypanosoma cruzi isoladas de humanos de três áreas endêmicas de Minas Gerais Biodemes of Trypanosoma cruzi strains isolated from humans from three endemic areas in Minas Gerais State

Co-authors: Marise Mattos: Oswaldo Cruz Foundation – Evandro Chagas Clinical Research Institute, Rio de Janeiro, Brazil Eliezer Benchimol: Oswaldo Cruz Foundation – Evandro Chagas Clinical Research Institute, Rio de Janeiro, Brazil Elisa Cupolillo: Oswaldo Cruz Foundation – IOC-Department of Immunology, Rio de Janeiro, Brazil Tulia Cuzzi-Maya: Oswaldo Cruz Foundation – Evandro Chagas Clinical Research Institute, Rio de Janeiro, Brazil Claude Pirmez: Oswaldo Cruz Foundation – IOC-Department of Biochemistry and Molecular Biology, Rio de Janeiro, Brazil Gabriel Grimaldi Junior: Oswaldo Cruz Foundation – IOC-Department of Immunology, Rio de Janeiro, Brazil

BLEPHARO-CONJUNCTIVITIS DUE TO LEISHMANIA (VIANNIA) BRAZILIENSIS CUTANEOUS INFECTION - Report of two cases in Rio de Janeiro, Brazil Corresponding author:

Claude Pirmez

Papers

Detection of Leishmania DNA by Polymerase Chain Reaction in Scars of Treated Human Patients

A Low-Dose Antimony Treatment in 159 Patients with American Cutaneous Leishmaniasis: Extensive Follow-up Studies (Up to 10 Years)

Treatment of American cutaneous leishmaniasis: a comparison between low dosage (5 mg/kg/day) and high dosage (20 mg/kg/day) antimony regimens.

Biodemas de cepas do Trypanosoma cruzi isoladas de humanos de três áreas endêmicas de Minas Gerais Biodemes of Trypanosoma cruzi strains isolated from humans from three endemic areas in Minas Gerais State

BLEPHARO-CONJUNCTIVITIS DUE TO LEISHMANIA (VIANNIA) BRAZILIENSIS CUTANEOUS INFECTION - Report of two cases in Rio de Janeiro, Brazil Corresponding author: