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Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis.

ABSTRACT: Mucocutaneous leishmaniasis is caused by infections with intracellular parasites of the Leishmania Viannia subgenus, including Leishmania guyanensis. The pathology develops after parasite dissemination to nasopharyngeal tissues, where destructive metastatic lesions form with chronic inflammation. Currently, the mechanisms involved in lesion development are poorly understood. Here we show that metastasizing parasites have a high Leishmania RNA virus-1 (LRV1) burden that is recognized by the host Toll-like receptor 3 (TLR3) to induce proinflammatory cytokines and chemokines. Paradoxically, these TLR3-mediated immune responses rendered mice more susceptible to infection, and the animals developed an increased footpad swelling and parasitemia. Thus, LRV1 in the metastasizing parasites subverted the host immune response to Leishmania and promoted parasite persistence.

SUBMITTER: Ives A

PROVIDER: S-EPMC3253482 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis.

Ives Annette A Ronet Catherine C Prevel Florence F Ruzzante Giulia G Fuertes-Marraco Silvia S Schutz Frederic F Zangger Haroun H Revaz-Breton Melanie M Lye Lon-Fye LF Hickerson Suzanne M SM Beverley Stephen M SM Acha-Orbea Hans H Launois Pascal P Fasel Nicolas N Masina Slavica S

Science (New York, N.Y.) 20110201 6018

Mucocutaneous leishmaniasis is caused by infections with intracellular parasites of the Leishmania Viannia subgenus, including Leishmania guyanensis. The pathology develops after parasite dissemination to nasopharyngeal tissues, where destructive metastatic lesions form with chronic inflammation. Currently, the mechanisms involved in lesion development are poorly understood. Here we show that metastasizing parasites have a high Leishmania RNA virus-1 (LRV1) burden that is recognized by the host ...[more]

PMID: 21311023

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Project description:BackgroundCutaneous leishmaniasis is caused by different protozoan parasites of the genus Leishmania. Leishmania RNA virus (LRV) was identified as the first Leishmania infecting virus in 1998. Different studies showed the presence and role of the LRV in Leishmania parasites causing cutaneous leishmaniasis (CL). However, there is limited data on the pooled prevalence of LRV in Leishmania parasites causing CL. Therefore, the aim of this systematic review and meta-analysis was to determine the pooled prevalence of LRV in Leishmania parasite isolates and/or lesion biopsies in patients with CL from the available literature globally.MethodologyWe retrieved the studies from different electronic databases. The studies were screened and identified based on the inclusion and exclusion criteria. We excluded studies exclusively done in experimental animals and in vitro studies. The review was conducted in line with PRISMA guidelines. The meta-analysis was performed with Stata software version 14 with metan command. The forest plot with random-effect model was used to estimate the pooled prevalence with 95% confidence interval. Inverse variance index (I2) was used to assess the heterogeneity among the included articles.Principal findingsA total of 1215 samples from 25 studies were included. Of these, 40.1% (487/1215) were positive for LRV. The overall pooled prevalence of LRV globally was 37.22% (95% CI: 27.54% - 46.90%). The pooled prevalence of LRV in the New World (NW) and Old World (OW) regions was 34.18% and 45.77%, respectively. Leishmania guyanensis, L. braziliensis, L. major, and L. tropica were the most studied species for the detection of LRV. The prevalence of LRV from Leishmania isolates and lesion biopsies was 42.9% (349/813) and 34.3% (138/402), respectively.ConclusionThis systematic study revealed that there is high prevalence of LRV in Leishmania parasites isolated from patients with CL. More comprehensive studies would be required to investigate the presence of the LRV in other Leishmania species such as L. aethiopica to fully understand the role of LRV in different clinical manifestations and disease pathology presented in CL patients.

Project description:Leishmaniasis is a major neglected tropical disease which contributes a huge economic burden on already meager economic resources. The World Health Organization (WHO) has estimated an annual incidence of 700,000--1,000,000 patients and about 20,000-30,000 deaths per year. Approximately 66,941 patients of cutaneous leishmaniasis are reported annually in the Americas. In recent years, Nicaragua has presented alarmingly high numbers of patients and elevated incidence rates. Unfortunately, there are no detailed spatial descriptions on the epidemiological situation of leishmaniasis in this country. The objective of this study is to present descriptive data about the epidemiology of leishmaniasis in Nicaragua in the context of the distribution of this neglected tropical disease (NTD) in the Americas. This paper also provides an epidemiological update on different forms of leishmaniasis found in the three administrative regions of Nicaragua and its municipalities. Health authorities from the Ministry of Health of Nicaragua (MINSA) provided the entomological and epidemiological information for the different forms of the disease from 2001 to 2018. Prevalence, incidence rates, clinical classification of disease, age groups, sex, and geographic distribution by municipality and department are described in this study. Approximately 90%-95% of the national patients corresponded to CL and 5-10% correspond to MCL. The disease is distributed in the three regions of the country, with a higher burden in the Departments of Jinotega, Matagalpa and Atlántico Norte. The municipalities with the highest proportion of patients were El Cuá (23.92%), Waslala (14.16), Santa Maria de Pantasma (9.62%), Rancho Grande (9.03%) and Siuna (7.67%). There is an expansion of spatial distribution of CL and MCL in the North Central and South Atlantic regions of the country. These results could inform interventional strategies to address the burden of leishmaniasis in Nicaragua, which would improve the likelihood of meeting the goals for the Leishmaniasis Plan of Action for the Americas.

Dataset Information

Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis.

Publications

Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis.

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