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Age-related alteration of arginase activity impacts on severity of leishmaniasis
25 Jun 2008
Maria Victoria Valero
Citation: Müller I, Hailu A, Choi B-S, Abebe T, Fuentes JM, et al. (2008) Age-Related Alteration of Arginase Activity Impacts on Severity of Leishmaniasis. PLoS Negl Trop Dis 2(5): e235. doi:10.1371/journal.pntd.0000235
Leishmaniasis remains a severe public health problem, with an estimated global prevalence of 12 million and a yearly incidence of 1.5–2 million cases: 1–1.5 million for cutaneous leishmaniasis and 500,000 for the visceral form VL (1). Multiple risk factors such as environmental changes and human behaviour are making leishmaniasis a neglected disease of growing importance. One of the key underlying issues is the unplanned displacement of populations. Socio-economic, demographic, cultural, religious, political and environmental determinants force people to migrate and to find new means to supply their basic needs. Due to these factors and to the social exclusion of migrant populations, there is according to recent evidence an increasing geographical overlap between VL and HIV/AIDS. This newly emerging co-infection pattern currently affects 34 countries around the world, leading to new challenges for the design and implementation of integrated control strategies (2).
Müller and colleagues tested the hypothesis that arginase mediated L-arginine metabolism is altered with age and in this manner modulates the capacity of macrophages to control parasite growth. The study evaluated the impact of ageing on the development of experimental leishmaniasis in genetically susceptible young (6–8 weeks) and older (12 monthss) BALB/c mice. The mice were infected with Leishmania major then parasite and lesion development, and parasite load were determined. The laboratory findings were compared with data from an endemic area in Ethiopia. Data from 37 patients with visceral leishmaniasis (VL) were used to determine the age distribution of VL.
The results showed that, after three weeks of infection, the disease pathology was exacerbated in young BALB/c mice. The parasite loads and arginase activities at the site of infection were significantly increased in both pre-pubertal and adult mice, as compared with aged mice. The authors also suggest that the level of arginase activity correlates with disease severity. Finally, activated macrophages from young mice provide a more permissive environment for parasite growth, directly linking the higher arginase activity to increased parasite replication. These findings were also reflected in the limited data from patients.
A variety of immunological, nutritional and genetic factors are associated with frequency and severity of infectious diseases at different stage of life (3). In young populations the susceptibility to diseases is higher, owing to the still maturing immune system. Exposure to diseases and successful treatments contribute to the development of acquired immunity with age. Therefore, infection load and disease are often the result of the dynamic interplay of environmental factors – i.e. exposure, parasite biology including resistance dynamics and host susceptibility.
The findings of this paper offer a basis for research seeking to develop new strategies to interrupt the process of Leishmania colonization of the macrophages, using a murine model as the basis for young human populations. It is hoped that these experimental and descriptive epidemiological studies are followed-up by thorough additional preclinical, clinical and field studies to establish the potential of new intervention strategies. Finally, such new approaches should not neglect the fact that leishmaniasis is a zoonosis.
1. Desjeux P (2001) .The increase in risk factors for leishmaniasis worldwide. Trans R Soc Trop Med Hyg; 95:239–243.
2. Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P, et al (2002). Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis; 2:494-501
2. Raguenaud M-E, Jansson A, Vanlerberghe V, Van der Auwera G, Deborggraeve S, et al (2007). Epidemiology and clinical features of patients with Visceral Leishmaniasis treated by an MSFClinic in Bakool Region, Somalia, 2004–2006. PLoS Negl Trop Dis; 1(1): e85. doi:10.1371/journal.pntd.0000085.
© 2008 Müller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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