The effect of age on the frequency of adverse reactions caused by antimony in the treatment of American tegumentary leishmaniasis in Governador Valadares, State of Minas Gerais, Brazil

Diniz, Doracy; Costa, Alexandre Sylvio Vieira da; Escalda, Patrícia Maria Fonseca

doi:10.1590/s0037-86822012000500011

Cited by 14 publications

(17 citation statements)

References 10 publications

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“…A previous study showed that in the treatment of ATL most of adverse events occur in subjects over 50 years of age [40]. While it is an interesting observation, our trial was not powered to detect differences among subgroups and these results serve to suggest that subjects over 50 years old may be a suitable group to assess in further studies.…”

Section: Discussionmentioning

confidence: 89%

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil

et al. 2017

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BackgroundAlthough high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute.MethodsA single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924.ResultsOverall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7–29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1–31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony.ConclusionsCompared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.

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Section: Discussionmentioning

confidence: 89%

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil

et al. 2017

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“…9 Most data related to the disease in the elderly, defined as older than 65 years for men and 60 years for women, come from epidemiologic and clinical studies with the participation of few elderly patients. 10 In a retrospective study comparing CL in young versus senior patients, we found that patients older than 60 years were more likely to have a previous history of CL, less lymph node enlargement, and higher frequencies of ML and DL. In this study, we also documented that older patients produced less interferon (IFN)-γ and more interleukin (IL)-10 than young patients.…”

Section: Introductionmentioning

confidence: 82%

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

Lago

Nascimento

Carvalho

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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There is evidence that elderly patients with cutaneous leishmaniasis (CL) have more mucosal and disseminated diseases than young patients and their cells produce less antigen-induced interferon (IFN)-γ. Herein, we compared the roles of interleukin (IL)-10 and IL-15 as modulators of antigen-induced immune responses and the incidence of adverse reaction and response to therapy in young versus elderly patients with CL. Study participants included 35 senior (60-85 years) and 35 young (18-40 years) patients who had a diagnosis of CL documented by typical cutaneous lesions containing DNA. Elderly patients had less lymph node enlargement. Antigen-induced blood cell cytokine responses were studied in the absence or presence of IL-10 antibody or exogenously added recombinant IL-15. The ratio of IFN-γ/IL-10 was lower in elderly patients, and IFN-γ production was enhanced by either neutralization of IL-10 or exogenous recombinant IL-15 in blood cells from elderly but not young patients. Patients were treated three times weekly with antimony at 20 mg/kg/day for 20 doses. Although there was no difference in response to therapy between the two groups, two young patients needed rescue therapy with amphotericin B. Ventricular arrhythmias and ventricular overload were more frequent in elderly patients. We conclude that elderly patients have alterations in the immune response that may influence clinical manifestations, but we did not find that they had a higher failure rate than young subjects to antimony therapy. However, because of the high rate of electrocardiographic abnormalities during therapy, antimony should not be used in elderly patients with CL.

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“…8 Moreover, age has been an important factor regarding side effects caused by antimony therapy. 9,10 Epidemiologic studies have pointed out that ATL occur predominantly in young subjects, a population that is more exposed to sand fly bites. 4 However, cohort studies have shown an increasing number of elderly present with CL 2,4 and it is well known that ML and DL occur more in adults than in children.…”

Section: Introductionmentioning

confidence: 99%

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

Carvalho¹,

Amorim²,

Barbosa³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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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.

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The effect of age on the frequency of adverse reactions caused by antimony in the treatment of American tegumentary leishmaniasis in Governador Valadares, State of Minas Gerais, Brazil

Cited by 14 publications

References 10 publications

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil

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

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

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