Mechanisms Relating to the Distinct in Vitro Susceptibility of Human Macrophages to L. Viannia Infection

2014-08-27 03:41:32 | BioPortfolio


The purpose of this study is to determine how the body defends itself against Leishmania (Viannia), a parasite that can cause a skin infection and skin sores. Certain cells in the immune system act more aggressively against Leishmania in people with mild Leishmania symptoms than in those who have long-term or recurring symptoms of the disease. Participants in the study will include people who currently have Leishmania infection, people who have had the infection in the past, and people who have never been exposed to the parasite. This study will enroll 220 adults, ages 18 to 70 years, at 3 sites in Colombia. Blood samples will be collected from volunteers at least once during the study. Participants will also undergo HIV testing. Volunteers will participate in up to 2 study visits, scheduled 2-3 weeks apart.


This is a cross-sectional study that aims to determine the mechanisms that lead to the distinct in vitro susceptibility of human macrophages to L. Viannia infection, and their relationship to clinical phenotype. It is the third part of a study which includes DMID protocols 06-0009 and 06-0010. The general objective of the study is to determine the mechanisms that lead to the distinct in vitro susceptibility of human macrophages to L. Viannia infection, and their relationship to clinical phenotype. (Understanding the immune mechanisms underlying disease should provide insight for the development of new methods for treatment and intervention.) The specific objectives of the study are: to determine the association of the Toll response profile of monocytes and macrophages with the in vitro susceptibility phenotype, and analyze Toll receptor response in relation with both in vitro and clinical phenotype in participants presenting asymptomatic, chronic and recurrent disease and in healthy donors (controls)(Toll receptors); to determine gene expression response of susceptible and resistant macrophages to exposure and infection by L. panamensis, in order to identify genes and gene products that determine the course of infection in the host cell and that are linked to clinical response; to define the interaction of cytokines and Leishmania infection in promoting the latent persistence of infection or activation of growth, and to explore the role of apoptosis in elimination or propagation of infection (Apoptosis); and to determine the functional phenotypic characteristics of susceptible and resistant macrophages from healthy donors and clinically disparate individuals by flow cytometric analyses (Functional Phenotype of mononuclear phagocytes). Participants of the four specific objectives will be asked to provide relevant demographic, clinical and epidemiologic information and blood samples. Monocytes and macrophages differentiated from peripheral blood samples will be analyzed by different methodologies (flow cytometry, Real time PCR, ELISA and microarray analysis), and the results compared across the groups in order to determine if the macrophage response to infection is a determinant of recurrent and/or chronic disease development. Participants will be enrolled at three sites in Colombia: CIDEIM, Cali; CIDEIM, San Andrés Hospital, Tumaco; and San Juan Bautista Hospital, Chaparral. Patients (males and females) aged between 18-70 years with historic chronic or recurrent cutaneous leishmaniasis diagnosed at any of these three study sites will be invited to participate in the study. Asymptomatic and healthy donors (controls) will also be enrolled. A maximum of 220 participants will be enrolled. For historic (chronic and recurrent) and asymptomatic participants, a single study visit is planned. For healthy donors, 2 study visits are planned. The second visit will be programmed 2-3 weeks after the first visit. Study outcome measures will be levels of transcription of cytokines (e.g. TNF-alpha, IL-10, IL-12) and nuclear transcription factors normalized to the number of macrophages; percentage of non-infected and infected macrophages/monocytes expressing specific cytokine receptors and Toll like receptors; density of receptor expression; percentage of apoptotic cells; number and change in number of parasites in apoptotic and non-apoptotic cells; nitric oxide level; cytokine production as concentration of supernatants of macrophage cultures (e.g. TNF-alpha, IL-10, and IL-12); intracellular cytokine production, intracellular nitric oxide level; percentage of infected macrophages/monocytes and number of intracellular parasites over time to assess survival and replication; and percentage of non-infected and infected macrophages/monocytes expressing specific activation and differentiation markers and the intensity of marker expression.

Study Design

Time Perspective: Prospective




Centro Internacional de Entrenamiento e Investigaciones Medicas, CIDEIM




Yale University

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:41:32-0400

Clinical Trials [72 Associated Clinical Trials listed on BioPortfolio]

Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396

The primary objective of this protocol is to treat laboratory confirmed cutaneous leishmaniasis with WR 279,396 in military health care beneficiaries. In this study "cutaneous leishmaniasi...

Miltefosine to Treat Cutaneous Leishmaniasis in Bolivia

Cutaneous leishmaniasis is typically treated with the parenteral product pentavalent antimony. Miltefosine is an oral agent shown to be active for mucosal leishmaniasis due to L braziliens...

Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World

The objective of this study is to determine the effectiveness and toxicity of WR 279,396, a topical cream for the treatment of cutaneous leishmaniasis. This study is to be conducted with ...

Safety and Efficacy Study of Paromomycin to Treat Visceral Leishmaniasis

Symptomatic Visceral Leishmaniasis(VL)is fatal; Due to the increasing resistance to standard therapy with antimonials, there is a need for new safe, efficacious, low-cost therapies for the...

Miltefosine to Treat Mucocutaneous Leishmaniasis

The purpose of this Treatment IND is to make miltefosine available for mucocutaneous leishmaniasis patients presenting in the United States. If entrance criteria are met, subjects with mu...

PubMed Articles [210 Associated PubMed Articles listed on BioPortfolio]

Efficacy of Apigenin and Miltefosine Combination Therapy against Experimental Cutaneous Leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by several different species of Leishmania. Treatment of leishmaniasis involves a limited drug arsenal that is associated with severe side effects,...

Double trouble: visceral leishmaniasis in twins after traveling to Tuscany - a case report.

Leishmaniasis is endemic in many countries worldwide, with a prevalence of 12 million people infected, and an estimated annual incidence of 500 000 visceral leishmaniasis cases. In Europe visceral lei...

Atypical leishmaniasis: A global perspective with emphasis on the Indian subcontinent.

Among the neglected tropical diseases, leishmaniasis continues to be prevalent in many tropical and subtropical countries despite international, national, and local efforts towards its control and eli...

Tamoxifen and meglumine antimoniate combined therapy in cutaneous leishmaniasis patients: a randomized trial.

There is a clear need for new strategies of leishmaniasis treatment. This work was conducted to evaluate the efficacy of the co-administration of tamoxifen and meglumine antimoniate (Sb ) in a phase I...

Uncharted territory of the epidemiological burden of cutaneous leishmaniasis in sub-Saharan Africa-A systematic review.

Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis, with 0.7 to 1.2 million cases per year globally. However, the burden of CL is poorly documented in some regions. We carried out...

Medical and Biotech [MESH] Definitions

A disease caused by any of a number of species of protozoa in the genus LEISHMANIA. There are four major clinical types of this infection: cutaneous (Old and New World) (LEISHMANIASIS, CUTANEOUS), diffuse cutaneous (LEISHMANIASIS, DIFFUSE CUTANEOUS), mucocutaneous (LEISHMANIASIS, MUCOCUTANEOUS), and visceral (LEISHMANIASIS, VISCERAL).

A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals including rodents. The Leishmania mexicana complex causes both cutaneous (LEISHMANIASIS, CUTANEOUS) and diffuse cutaneous leishmaniasis (LEISHMANIASIS, DIFFUSE CUTANEOUS) and includes the subspecies amazonensis, garnhami, mexicana, pifanoi, and venezuelensis. L. m. mexicana causes chiclero ulcer, a form of cutaneous leishmaniasis (LEISHMANIASIS, CUTANEOUS) in the New World. The sandfly, Lutzomyia, appears to be the vector.

A parasitic hemoflagellate of the subgenus Leishmania viannia that infects man and animals. It causes cutaneous (LEISHMANIASIS, CUTANEOUS), diffuse cutaneous (LEISHMANIASIS, DIFFUSE CUTANEOUS), and mucocutaneous leishmaniasis (LEISHMANIASIS, MUCOCUTANEOUS) depending on the subspecies of this organism. The sandfly, Lutzomyia, is the vector. The Leishmania braziliensis complex includes the subspecies braziliensis and peruviana. Uta, a form of cutaneous leishmaniasis in the New World, is caused by the subspecies peruviana.

An endemic disease that is characterized by the development of single or multiple localized lesions on exposed areas of skin that typically ulcerate. The disease has been divided into Old and New World forms. Old World leishmaniasis is separated into three distinct types according to epidemiology and clinical manifestations and is caused by species of the L. tropica and L. aethiopica complexes as well as by species of the L. major genus. New World leishmaniasis, also called American leishmaniasis, occurs in South and Central America and is caused by species of the L. mexicana or L. braziliensis complexes.

A parasitic hemoflagellate of the subgenus Leishmania viannia that infects man and animals and causes mucocutaneous leishmaniasis (LEISHMANIASIS, MUCOCUTANEOUS). Transmission is by Lutzomyia sandflies.

More From BioPortfolio on "Mechanisms Relating to the Distinct in Vitro Susceptibility of Human Macrophages to L. Viannia Infection"

Quick Search


Relevant Topics

Wound management
Anything that breaks the skin is a wound because when the skin is broken, there's a risk of germs getting into the body and causing an infection. Follow and track Wound Care News on BioPortfolio: Wound Car...

Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Acne Dermatology Eczema Psoriasis Wound Care Dermatology is the medical specialty concerned with the diagnosis and treatment of skin disorders (Oxford Medical Dictionary). As well as studying how the skin works, dermatology covers...

Searches Linking to this Trial