Epidemiological studies on zoonotic leishmaniasis and new trials for studying the effect of melatonin on the parasite
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Universidad de Granada
Departamento
Universidad de Granada. Departamento de MicrobiologíaMateria
Leishmaniasis Enfermedades parasitarias Enfermedades por protozoos Diagnóstico Terapéutica Medicina clínica Melatonina
Materia UDC
616.9 3207
Fecha
2016Fecha lectura
2015-11-10Referencia bibliográfica
Kotb Abd Elghany Elmahallawy, E. Epidemiological studies on zoonotic leishmaniasis and new trials for studying the effect of melatonin on the parasite. Granada: Universidad de Granada, 2016. [http://hdl.handle.net/10481/42676]
Patrocinador
Tesis Univ. Granada. Programa Oficial de Doctorado en: Medicina Clínica y Salud Pública; The study was supported in part by CTS-109 group from the Junta de Andalucía (Spain).Resumen
Leishmaniasis remains an important public health problem caused by protozoan of genus
Leishmania and transmitted by the bite of a female phlebotomine sand fly. Humans, rodents, and
some animal species are considered reservoir for the disease. Among other animal species, the
dogs are the most important reservoirs in a domestic environment, maintaining the endemic
focus of the parasite. The disease has been also linked to tropical and subtropical regions besides
being an endemic disease in the Mediterranean basin and South America. Depending on the
infecting parasite species and host immune response, three forms of the disease are known:
cutaneous, mucocutaneous, and disseminated visceral leishmaniasis of fatal prognosis.
The recent years have witnessed extraordinary potential progress and ever growing in organ
transplantation worldwide as a consequence of sustained economic growth and the higher
investments in tertiary healthcare policies in many developing countries. Spain is widely known
as one of the countries with the highest transplant rates. As result of lack of routine serology for
blood or organ donors in areas of high endemicity, transplanted recipients are susceptible to a
broad spectrum infectious agents resulting in different symptoms. Leishmania is considered one
of opportunistic infections but it is not common disease among transplanted patients, however,
the growing pool of transplant survivors and high migration dynamics steadily increases the
numbers of infected cases among transplant recipients especially among renal transplanted
recipients mainly in southern Europe, particularly with visceral leishmanisis (VL).
Despite several leishmanial researches, many questions are still unanswered. Early case detection
followed by adequate treatment represents the key to the control of the disease that may improve
the prognosis and can reduce transmission. Diagnosis of Leishmania infection is still somewhat
controversial due to absence of gold standard technique that appears mandatory to establish
effective strategic programmes. Current tools of diagnosis are several and they rely mainly on
parasite detection by microscopic examination or by molecular biology-based assays for
detecting parasite DNA (PCR) but none of these methods have become popular in field
diagnosis. The conventional parasitological techniques are also risky, time consuming, invasive
for the patient and require skilled personnel. The molecular methods also require the availability
of software, probes and primers, which cannot easily applied especially in field settings and still
not affordable for many clinical and scientific laboratories in developing countries. Interestingly, serological diagnosis using several tests is an alternative tool for the parasitological
diagnosis; can be used for a large-scale and decentralized diagnosis, however, all the serological
techniques share many drawbacks like that related to sensitivity or specificity have been
reported.
On the other hand, the presence of different Leishmania species and various manifestations also
complicates the therapeutic approach, especially in immunocompromised patients. A limited
number of effective antileishmanial agents are available for chemotherapy, and many of them are
expensive with severe side effects or have a markedly reduced effectiveness due to the
development of drug resistance. Based upon several published works, plants have different
biologically active compounds in their organs, which can be pharmacologically studied.
Melatonin is an indoleamine synthesized and released by several organs. Several studies have
included the relationship between melatonin and many parasitic or viral diseases.
Given above information, there is a genuine need to develop a novel effective and less toxic
antileishmanial drug for amelioration of patient’s life quality besides the necessity for surveying
strategy using a rapid and reliable diagnostic test in one of animal reservoirs in certain endemic
area (cats).
The scheduling of the thesis has been divided into several phases: the first part includes reviews
of the literature about current status of epidemiology, development in diagnosis and treatment of
the disease for better understanding the gaps in disease management. The second part of the
thesis, the experimental part, includes two phases; the first phase of the present work included a
serological study about Leishmania infection among transplanted organ recipients from southern
Spain followed by assessment of the occurrence of Leishmania infantum in domestic cats from
an endemic region in North-western Italy, by the association of both serological and molecular
tests. In the second phase of our work, we have studied the effect of melatonin against the
parasite in vitro.
Our results provide an evidence that a relatively high prevalence of L.infantum was recorded
among kidney transplanted recipients, where 30 (4.08%) samples were positive for L. infantum
out of 625 examined serum samples. Regarding the cross sectional survey in cats, we have found that 33 samples (13.12%) were positive for L. infantum out of 250 examined serum samples from
cats, whereas of the 282 blood samples, 80 (28.37%) were positive.
In accordance with therapeutic trials, melatonin not only demonstrated a significant
antileishmanial activity in vitro but was also accompanied by an alteration of the several
mitochondrial parameters, including calcium homeostasis and by changes in some mitochondrial
parameters critical to parasite survival.
These multiple results suggest that 1) the routine serological testing for VL should be initially
considered before undergoing transplantation for both donor and recipient transplant patients
living or traveling in endemic areas to prevent such serious post-transplantation infection, 2)
High prevalence of L.infantum among cats in the studied area which show the importance of cats
not only as reservoir for the disease, but also the need for further future research for accurate
diagnosis of this zoonosis, 3) Western blot and PCR would be a novel potential tools in diagnosis
of Leishmania infection in cat, and 4) melatonin may be a potent antileishmanial agent, and
therefore further research is warranted to elucidate the effects of melatonin in vivo and in
association with other antileishmanial drugs combined with examination the role of melatonin
receptors in these effects and their underlying mechanisms. These observations together could be
of special attention for the people to identify the risk factors of transmission of such protozoan
and would be helpful in earlier detection, treatment and as a consequence in eradication of this
neglected disease.