Immunogenetics of Visceral Leishmaniasis
Visceral LeishmaniasisVisceral leishmaniasis is a potentially fatal disease caused in South America by the protozoan Leishmania chagasi. In neighborhoods with high exposure rates, the outcome of human infection with L. chagasi ranges from asymptomatic to a disseminated wasting disease called visceral leishmaniasis (VL). Several studies document familial clustering of VL in populations at risk. Segregation analyses favor a genetic over an environmental model for susceptibility to L. chagasi infection. A peri-urban outbreak of VL near the Universidade Federal do Rio Grande do Norte (UFRN) in Natal, northeast Brazil, has allowed us to identify endemic neighborhoods with ongoing transmission of L. chagasi infection. Natal is ideal for this study because endemic neighborhoods are easily accessible, people are motivated to cooperate with measures to control VL, and other forms of leishmaniasis are not transmitted in the region. Dr. Jeronimo of the UFRN, and Dr. Mary Wilson at University of Iowa have collected clinical data and DNA from 400 VL families living in these endemic neighborhoods. We have created an unprecedented cohort through which we can identify four distinct phenotypic responses after L. chagasi exposure. We documented familial clustering of L. chagasi infection, and results of both correlation and segregation analyses are consistent with the hypothesis that genetic factors predispose, in part, to the diverse clinical outcomes after infection. Polymorphism in the TNF locus is associated with developing symptomatic as opposed to asymptomatic disease after infection. We recently completed a genome-wide scan of the quantitative immune response (DTH) and identified potential linkage regions on chromosomes 2, 13, 15 and 19. We have also identified a small linkage peak on chromosome 9 for VL. In our ongoing study, we will next perform fine mapping of these regions using dense SNPs to identify genes that may determine susceptibility to L. chagasi infection. Additionally, we will also analyze candidate genes for association/linkage with susceptibility to or protection from L. chagasi disease. We recently identified an association on chromosome 5 with the DTH immune response among two linkage disequilibrium blocks spanning multiple immune related genes.
Clinical Investigation of Infections Due to Leishmanial Parasites
LeishmaniasisLeishmaniasis1 moreMechanisms of host immune response to intracellular protozoa will be investigated in patients with naturally acquired infection employing a variety of in-vitro techniques. Both non-specific and antigen-specific humoral and cellular immune responses will be assessed. Parasites will be isolated from patients, cultivated in-vitro, and characterized. Responses to chemotherapy will be assessed parasitologically, immunologically and clinically.
Prospective Observational Study of Intralesional Treatment With Pentostam in Cutaneous Leishmaniasis...
Cutaneous LeishmaniasisCutaneous leishmaniasis (CL) is endemic in Israel and is caused by Leishmania major or Leishmania tropica. CL is usually a benign disease and limited to the skin. One of the local treatment available is intralesional (IL) Pentostam injection. During the current study the investigators will monitor the adverse effects of this treatment and will follow up the recovery of the lesions after Pentostam injections.
Immune Response of Visceral Leishmaniasis PatientsTreated With Antimonial Plus N-Acetylcysteine...
Visceral LeishmaniasisImmune Response1 moreThis study is designed to evaluate the immune and therapeutic responses of visceral leishmaniasis patients using N-acetylcysteine (NAC) as an adjuvant therapy to pentavalent antimony.
LAMP Assay for the Diagnosis of Visceral Leishmaniasis
Visceral LeishmaniasisThis study will evaluate the of the loop-mediated amplification assay (LAMP) as a diagnostic as well as a Test-of-Cure (ToC) for visceral leishmaniasis (VL) in an endemic area in Ethiopia. Furthermore, we aim to further development of the direct-blood PCR-Nucleic Acid Lateral-Flow Immuno-Assay (dB-PCR-NALFIA) as a novel diagnostic tool for VL and its subsequent evaluation in the field.
Compassionate Use of Sodium Stibogluconate (Pentostam) for Cutaneous and Mucocutaneous New World...
LeishmaniasisCutaneous2 morePatients with biopsy proven new world cutaneous or mucocutaneous leishmaniasis will be treated with sodium stibogluconate (Pentostam).
Frequency of Parasite Infection in Hyraxes and Sandflies During Outbreak of Leishmania Tropica Epidemic...
Cutaneous LeishmaniasisThe objective of the project is to study the pathogenesis of Leishmania tropica infection in a focus of infection, to learn about relationship of infection in humans with ecological factors such as infection in hyraxes reservoir hosts and vector sandflies
Mediterranean Visceral Leishmaniasis With Leishmania Infantum
LeishmaniasisL. infantum leishmaniasis is endemic in the South of France. For several years, there has been an expansion of the territory of sandflies (vector of leishmaniasis), with the appearance of cases of canine leishmaniasis in new outbreaks: West of the Occitania region (South-West). The transition from asymptomatic to disease depends largely on the immune status of the carrier, but many other factors specific to the parasite and host remain poorly defined. Asymptomatic carriage is present in a large majority of infected subjects, however, to date, only parasite isolates causing the patent form have been characterized. In this PHRC, the team wishes to study the genetics of parasite isolates present in asymptomatic carriers of the Alpes-Maritimes outbreak and the new Occitanie outbreak as well as the genetics of the host. The primary objective is the genetic characterization of L. infantum isolates by the microsatellite method, present in asymptomatic carriers in southeast and southwestern France. The secondary objectives are: Comparison of the genetic profiles of L. infantum isolates, by microsatellite method, from asymptomatic carriers of the new Southwestern outbreak with isolates from asymptomatic carriers of the historical Southwestern outbreak. Comparison of the genetic profiles of L. infantum isolates, by the microsatellite method, present in asymptomatic carriers in the Southeast with the profiles of isolates present in patients in the same outbreak, for whom a microsatellite study has already been obtained previously. the team is also conducting a preliminary study of the host genetic factors that would be associated with asymptomatic carriage by studying the association between potential host-related genetic risk factors (HLA typing, NLRP3 gene study) and asymptomatic carriage. Indeed, a recent study showed that the NLRP3 gene prevents the development of the patent form of leishmaniasis in the mouse model. This preliminary genetic study will identify potential host-related factors associated with asymptomatic carriage. To meet these objectives, leuco-platelet layer parasites (CLP) obtained via EFS from the 2 sources of interest will be isolated. This project is a research not involving the human person. It is multicentric and non-randomized. As a result of this research, isolates from asymptomatic carriers of the historical outbreak will be studied and compared to those present in new endemic outbreaks, as well as to those of patients already studied in a previous study. A better knowledge of parasites circulating in asymptomatic carriers will make it possible to study in a comprehensive way the risk factors associated with the parasite. In addition, the study of asymptomatic carrying in new endemic outbreaks such as Occitania is very original, since no human studies have yet been undertaken in this region. The results obtained in this PHRC will be used to understand the factors associated with the development of visceral leishmaniasis.
Evaluation of a Diagnostic Device, CL Detect™ Rapid Test, for the Diagnosis of Cutaneous Leishmaniasis...
LeishmaniasisCutaneousDetermine the sensitivity and specificity of the FDA-cleared CL Detect™ Rapid Test in Peru, using a test procedure that was modified from that described in the device instructions to optimize these parameters for the detection of Leishmania species identified in Peru.