Leishmaniosis is basically characterized by an anomaly antigen response to an altered immune system function. It therefore seems logical to assume that the use of such immune-stimulant substances, either alone or associated with traditional medication, can favorably influence the outcome of therapy. The results show that both types of Leishmaniae are sensitive to zinc sulphate.
Notes on the biological cycle of Leishmania
The infection is transmitted by the bite of infected sandflies. The promastigotes (flagellates elements, extracellular) in the insect’s saliva, penetrate through the skin, bind to macrophages of the skin and spread in the reticuloendothelial system of the whole organism. On the surface of the promastigote there are two molecules that have a prominent role in engaging the parasite-phagocytic cells: a glycoprotein (gp63) and a lipofosfoglycan. They activate the way alternates complement. Most parasites are destroyed by the body’s non-specific defenses, some are rapidly engulfed by macrophages, where they become amastigotes (aflagellati elements, intracellular), which begin to multiply in intracellular vacuoles. The amastigotes are oval forms of 2-4 microns in diameter. The lysosomes of macrophages release the hydrolasic enzymes to digest the parasite, Leishmania but offer some resistance to their action. Visceral leishmaniosis in the affected cells are soon to meet death and release the amastigotes that are themselves engulfed by other macrophages: this cycle is repeated several times until all organs containing macrophages are widely infected with Leishmaniae (spleen, liver, bone marrow, lymph nodes). When a subject is infected point from another phlebotomist not yet infected, the infection is transmitted at the time when it sucks the blood, through the circulating macrophages full of amastigotes. In the sandfly stomach amastigotes are released in a few hours and intestines are transformed into promastigotes, 10-15 microns long plagued shape and 1.5-3.5 microns wide: the scourge measures 15-28 microns. After many binary divisions they migrate into the pharynx and in the buccal cavity of the sandfly, ready to be placed on a new host. The cycle time in the mosquito is ten-day.
The immune system in leishmaniosis
Leishmaniosis is basically characterized by an anomaly antigen response to an altered immune system function.
The Leishmaniae, through antigenic system, can disrupt the host’s defense system. Already in 1985 Bunn Moreno et al. (1) described the presence of a depressing factor on lymphocytes “suppressor T” and a stimulating factor on B lymphocytes, this would result in hyper-stimulation of the humoral and cell-mediated alteration of that. Therefore many clinical manifestations are related to the immune response more than to a precise direct action of the parasite L. Ceci, M. Sasanelli, G.Carelli, 1989 (2) . Also in the infected dog was shown that the ability of phagocytosis of monocytes, cell-response, is significantly reduced, compared to that in healthy dogs, both in respect of the same Leishmaniae both against other microorganisms. It seems therefore logical to assume that the use of such immunostimulant substances, either alone or associated with traditional medication, can favorably influence the outcome of the therapy – P.Tassi, 1989 (3).
Some researchers are studying, since few years, the use of zinc sulfate in the treatment of cutaneous and visceral leishmaniosis (Kala Azar) man (Sharquie & Al-Azzawi 1996 (4); Sharquie et al.1997 (5)). The results are extremely interesting and such as to greatly reduce the healing time. Investigations conducted in vitro have indicated the possible sensitivity of Leishmania to zinc sulfate (Sharquie & Al-Azzawi 1996).
In 1998 R.A. Najin (6) led, both in vitro and in vivo, a study about the use of zinc sulfate in the therapy of leishmaniosis; be noted that in the animal model the zinc sulphate was administered orally. In this work has been assessed the sensitivity in vitro of promastigotes and axenic amastigotes of Leishmania major and tropical to zinc sulfate; the DL50 was calculated and compared to treatment standard being cutaneous leishmaniosis with pentavalent antimony compounds: meglumine antimoniate (GlucantimR) and sodium stibogluconate (PentostamR). The results show that both types of Leishmaniae are sensitive to zinc sulphate. Furthermore, the sensitivity of both types of Leishmania was evaluated according to the method of the smear on the slide and the results were compared to those obtained by standard methodology. Furthermore, the zinc sulfate administered Os was tested both in vivo for therapy or for prophylaxis. The results showed the efficacy of zinc sulfate in both kind of application. These results encourage the oral use of zinc sulfate in the clinical treatment of human cutaneous leishmaniosis. We have therefore decided to propose to Veterinary the work of Rafild A. Najiam et al. (1998). As for the effectiveness of zinc sulfate in the treatment of cutaneous leishmaniosis we refer to the article; we draw your attention briefly to the table, taken from the article, where it can be seen as both amastigotes that promastigotes are markedly more sensitive to zinc sulphate than pentavalent antimony compounds. It should be noted that the authors indicate that the DE50 for the sulfate of zinc is 59 mg / kg. The mechanism of action of zinc sulfate in the therapy of leishmaniosis therefore seems to be of interest to two separate paths: the first is given by the direct action of Zn on amastigotes such as to inhibit the proliferation, while the second is due to the immunomodulating and immunostimulating effects of zinc is against the “shift” in Th1 Th2, alteration of cell-mediated immune response and consequent deficiency (Sprietsma JE, 1997- 7), that as a stabilizing cell membranes for the antioxidant activity towards free radicals. In this regard, it is recalled as above said relatively slaughter of the plasma concentrations of Zn, Fe, Cr in the course of chronic infectious diseases. It must also not be overlooked the dermo-protective role of this trace element in the skin-trophism; briefly reminded that L.Ferrer et al. in 1988 (8) in Spain shows that 72% of dogs suffering from leishmaniosis presents skin lesions while R.J. Slappendel (9) in the Netherlands describes them in 90% of cases. In the study by R.A. Najim there are two other extremely interesting data: the first concerns the oral administration of zinc sulphate, while the second refers to the survey conducted in vivo on prophylactic Zn skills against cutaneous leishmaniosis. The prophylactic capacity of the zinc sulphate against L.major and tropical was evaluated in mice; two groups were set up: treated and controls. Was administered to subjects, orally, zinc sulfate for 5 consecutive days at a dose of 10 mg / kg while distilled water only to the controls. After 5 days the subjects were infected and controlled developed lesions weekly for two months. The subjects treated have developed significantly smaller lesions than controls. In our view this data, if confirmed on L.infantum, is an indication of extremely interesting both in the case of individuals who are already immunosuppressed, and therefore at greater risk, both for those living in endemic areas. Another interesting fact that emerges from the work of R. A. Najim is the method for the direct investigation of axenic amastigotes instead on promastigotes. It is known that the infection in the organism is propagated through the amastigotes and not through promastigotes.
These results encourage the oral use of zinc sulfate in the clinical treatment of human cutaneous leishmaniosis
The mechanism of action of zinc sulfate in the therapy of leishmaniosis therefore seems to be of interest to two separate paths: the first is given by the direct action of Zn on amastigotes such as to inhibit the proliferation, while the second is due to the immunomodulating and immunostimulating effects of zinc
This finding, if confirmed on L.infantum, is an indication of extremely interesting both in the case of individuals who are already immunosuppressed, and therefore at greater risk, both for those living in endemic areas
1)- Bunn-Moreno M.M., Madeira E.D., Miller K., Menezes J.A., Campo-Neto A.: “Hipergammaglobulinemia in Leishmania donova-ni infected hamster: possible association with a polyclonal activator of B cells and with suppression of T cell function“. Immun., 59:427-434, 1985
2)- Ceci L., Sasanelli M., Carelli G.: “Leishmaniosi canina: interazione ospite-parassita e patogenesi“. Ed. Grasso, 198)
3)- Tassi P.: “Leishmaniosi canina: terapia“. Ed. Grasso, 1989
4)- Sharquie K.E., Al-Azzawi K.E.: “Intralesional therapy of cutaneous leishmaniasis with 2% zinc sulphate solution“. Iraqi Central Organization for Specification & Quality Control/Patent section, Patent number 2583, Baghdad-Iraq, 1996
5)- Sharquie K.E., Najim R.A., Farjou I.B.: “A comparative control trial of intralesionally administered zinc sulfate, hypertonic saline, chloride and pentavalent antymony compounds against acute cutaneous leishmaniasis“. Clin. Exp. Dermatol. 22:169-173, 1997
6)- Najim R.A., Sharquie K. E., Farjou I.B.: “Zinc sulphate in the treatment of cutaneous Leishmaniasis: an in vitro and animal study” ” Mem. Inst. O. Cruz, Rio de Janeiro, 93(6):831-837, 1998
7)- Sprietsma J.E.: “Zinc-controlled Th1/Th2 switch significantly determines development of diseases” Med. Hypotheses 49(1): 1-14, 1997
8)- Ferrer L., Rabanal R., Fondevila D., Ramos J.A., Domingo M.: “Skin lesions in canine leishmaniasis” J. Small Anim.Pract., 29: 381-388, 1988
9)- Slappendel R.J.: “Canine leishmaniasis. A review based on 95 cases in the Netherlands“. The Vet. Quarterly 10: 1-16, 1988
NBF-Lanes thank Dr. Dr. Damiano Fortuna for his cooperation.
