Age Modifies the Immunologic Response and Clinical Presentation of American Tegumentary Leishmaniasis

Abstract

Abstract. Leishmania (Viannia) braziliensis is the main causal agent of American tegumentary leishmaniasis (ATL) that may present as cutaneous, mucosal, or disseminated cutaneous leishmaniasis. The disease is highly prevalent in young males and there is a lack of studies of ATL in the elderly. Herein, we compared clinical manifestations, immunologic response, and response to antimony therapy between patients 60 years of age (N = 58) and patients who were 21-30 years of age (N = 187). The study was performed in Corte de Pedra, Bahia, Brazil, a well-known area of L. braziliensis transmission. Cytokine production by cultured peripheral blood mononuclear cells stimulated with soluble Leishmania antigen was performed. Elderly subjects more frequently had a previous history of cutaneous leishmaniasis, large lesions, or mucosal leishmaniasis, and they were less likely to have lymphadenopathy. There was no difference regarding gender and response to therapy. Peripheral blood mononuclear cells from elderly subjects produced a similar amount of tumor necrosis factor than young patients but they produced less interferon-gamma and more interleukin-10 than young subjects. We concluded that elderly patients with cutaneous leishmaniasis should be searched for mucosal or disseminated leishmaniasis. The decreased interferon-gamma production and increase in interleukin-10 observed in elderly patients may contribute to parasite persistence and L. braziliensis infection dissemination.

The Elderly Respond to Antimony Therapy for Cutaneous Leishmaniasis Similarly to Young Patients but Have Severe Adverse Reactions

“…9,11 One possible explanation for these discordant findings could be the differences in the illness duration between the two groups, which was longer in the elderly than in young patients in previous studies. 9,11 Here, because the inclusion criteria limited the illness duration to between 30 and 60 days and because one of the matching criteria for control selection was a similar time of lesion duration, we did not detect any difference in ulcer size between the two groups. We confirmed the observation that there is a lower frequency and smaller size of satellite lymph nodes in elderly than young subjects.…”

“…We have previously shown that PBMCs from elderly patients with CL produce less antigen-induced IFN-γ and more IL-10 than PBMCs from young patients. 11 Here, we extended the characterization of the immune response by measuring IL-1β, CXCL9, and TNF levels in the two groups of patients. No significant difference was observed between the groups regarding the production of these cytokines (data not shown).…”

“…It has been shown that elderly patients with CL report a past history of CL and that their PBMCs produce less antigeninduced IFN-γ and more IL-10 than those of younger patients with CL. 11 As cured CL is thought to provide protective immunity against reinfection, these observations suggest that there might be a progressive impairment of immunologic memory and/or a less efficient type 1 immune response with age. Because IL-10 is the most important down-regulatory cytokine in leishmaniasis and IL-15 is an important cytokine in the induction of memory cells, we evaluated the influence of neutralization of IL-10 and exogenous addition of IL-15 in our patients.…”

“…In this study, we also documented that older patients produced less interferon (IFN)-γ and more interleukin (IL)-10 than young patients. 11 Because the pathogenesis of CL is dependent on the host immune response, [12][13][14][15] it is likely that alterations in the immune response may change not only the clinical presentation of the disease but also the response to therapy in the elderly. It is known that IFN-γ plays an important role in the control of Leishmania braziliensis infection, although an exaggerated and inappropriately modulated type 1 inflammatory response may cause tissue damage as observed in ML or DL.…”

Mucosal leishmaniasis: A Retrospective Study of 327 Cases from an Endemic Area of Leishmania (Viannia) braziliensis

“…Although we did not find an increase in children or women with mucosal disease, over the study period, there was an increase in the proportion of patients age 60 years and older. We know that infected sandflies can be documented inside of houses and in peridomiciliary areas, 24 which might increase the risk of exposure among children, women, and older adults who are more likely to spend time in these areas compared with young adult men who tend to do daytime agricultural work. The lack of an increase in the number of ML cases in children and women, however, makes it unlikely that the observed trend in older adults is related to a change in the transmission pattern.…”