Visceral leishmaniasis and potential role of vitamin D.

We read with special interest the recent article published in this Journal by Zaghi I et al. describing their case study of visceral leishmaniasis confirmed by liver biopsy [1]. The 59-year-old female had the initial hypothesis of hepatic and splenic metastases, based on her symptoms besides the nodular images revealed by the abdominal ultrasonography. Worthy of note was the hypercalcemia due to an excess of vitamin D, which was properly managed and led to successful control of her longstanding asthenia and loss of appetite. After the correct diagnosis was established by histopathologic studies, she underwent the specific anti-parasitic treatment resulting in complete regression of the nodular lesions. The authors emphasized that this was the first case report of several unsuspected foci of visceral leishmaniasis related to the antiinflammatory effect of hypervitaminosis D [1]. In this setting, with base on the literature data, the important role of proteases and micronutrient levels on the evolution of clinical manifestations, treatment responses, and outcomes of patients with Leishmania infections have merited a crescent interest [1–6]. Feleke BE et al. checked serum levels of micronutrients, just before and in the four initial weeks of treatment of leishmaniasis, to compare the patient profile with success rate [2]. The study included dosages of iodine, iron, selenium, zinc, and the vitamins A and D. They found lower levels of vitamin D in those patients with visceral leishmaniasis, a condition that persisted in spite of the adequate specific anti-leishmaniasis management. Gogulamudi VR et al. studied the effects of vitamins A and D3 to treat mice experimentally infected by L. donovani, and there was control of the parasite growth and infectivity [3]. The authors concluded that the utilization of the vitamins can reduce the parasitism and modulate the pro-inflammatory immune response to the anti-inflammatory activation, and the immune stimulation can have usefulness to control the visceral leishmaniasis [3]. Kumar VU et al. stressed the role of serum levels of the vitamins A, B, C, D, besides calcium, iron, and zinc on the responses to treatment and outcomes of leishmaniasis [4]. Defense mechanisms related to vitamin D can include the induction of antimicrobial peptides such as cathelicidin and the binding and killing of promastigotes in macrophages. The macrophage capacity of killing promastigotes (IFNactivated) may be reduced by vitamin D3, being associated with the cellular reduction of nitrous oxide production [4]. The authors concluded that the potential role of the cited micronutrients should be better evaluated for the public health management of leishmaniasis in the endemic regions [4]. Ribeiro-Dias F et al. reviewed the literature about the IL-32 in Leishmania infections, besides the role of vitamin D-dependent microbicidal pathway for parasite control [5]. They focused on the production of vitamin D-dependent peptides by human monocyte-derived macrophages with activity against Leishmania and Paracoccidioides brasiliensis. Besides, they commented differences between the human and mouse vitamin D pathways, such as nitrous oxide production in Leishmania infection and the role in parasite control, and suggested further research to better clear the evidence of IL32 isoforms during Leishmania infection, the IL-32 receptors, and the mechanisms of immune responses [5]. Sreedharan V et al. emphasized the role of Leishmania proteases in the parasite survival to complement-mediated lysis before the macrophage internalization, and inactivating the complement, breaking matrix proteins, and impairing the microbicidal mechanisms [6]. The main surface protease GP63, also known as zinc-metalloprotease, is present on the surface of Leishmania promastigotes, and can be used for development of new medicines. As without GP63, the Leishmania elicits inflammatory responses and limited infection, they concluded that further production of inhibitors targeting these proteases can be a new useful resource for the Leishmaniasis management, mainly in highly endemic regions [6]. The present short comments aim to highlight the value of a single case report that frequently enhances the interest of health-care workers about this very ominous infection.