Antileishmanial Activity of Lignans, Neolignans …
117
2 Leishmaniasis
Leishmaniasis, a disease listed in 2010 by the World Health Organization (WHO)
as one of the neglected diseases, is caused by parasites of the genus Leishmania
[17]. The WHO has attempted to control and eliminate leishmaniasis not only with
the development of effective ways of treatment, but, perhaps more importantly, by
prevention and control tools and programs. The list of actions taken is summarized
in the Global Vector Control Response 2017–2030 of WHO [18].
Leishmaniasis belongs to the parasitic, vector-borne group of diseases. The phlebotomine sandfly serves as the vector and more than 800 individual species of
such sandfly vectors have been identified to date. Only a small portion of them
(approximately 100 species) can transmit parasites pathogenic to humans [19, 20].
Leishmaniasis-related sandfly species are Lutzomyia, called “new world” species
(widespread in areas of Central and South America), and Phlebotomus, referred to
as “old world” species (widespread in areas of Europe, Asia, and Africa) [21]. In
terms of the development of leishmaniasis, the role of the sandfly vector is particularly important since the inner environment of the sandfly modulates the parasite’s
development and influences the final manifestation of the disease. Overall, the extent
of the disease manifestation results not only from the vector but also by variations in
the leishmanial parasite. To give a brief overview, linked below are different leishmanial species with the clinical manifestations of the illness and the area of occurrence
(Table 1) [22–24]. For this purpose, a simplified taxonomy of the Leishmania genus
has been employed that divides it into two main subgroups, Paraleishmania and
Euleishmania, which are further divided into the main subgenera, L. (Leishmania)
and L. (Viannia) [25]. The subgenus L. (Leishmania) relies on humans as the main
host reservoir, whereas in the case of L. (Viannia), humans are only an accidental
host [22–24].
From the life cycle viewpoint, leishmanial parasites are dimorphic organisms
inhabiting two different environments during their development. Within these two
periods, the parasite alternates between the promastigote and amastigote forms, with
the actual form determined by the environment. In the sandfly vector Phlebotomus
or Lutzomyia, the parasite lives in the form of promastigotes as a flagellated, extracellular organism, which needs to survive in conditions full of proteolytic enzymes
necessary for blood digestion [26–28]. After several specific interactions between
the sandfly gut and the parasite, the procyclic promastigotes are transformed into its
metacyclic form. The metacyclic form is covered with specific phosphoglycans that
gives the promastigote the necessary protection and also the means of interaction
(sandfly/parasite) [29–32]. In the metacyclic form, the parasite is motile, flagellated
and fully virulent due to the specific surface proteins (HASPs, SHERP or LPGlipophosphoglycans) [33–35]. During the time of procyclic/metacyclic transformation, the parasite migrates in the sandfly gut to the stomodeal valve. After reaching
this, the parasite destroys the stomodeal valve and causes a reflux of the parasite [36].
Consequently, when the sandfly is fed, the highly infective promastigote forms are
117
2 Leishmaniasis
Leishmaniasis, a disease listed in 2010 by the World Health Organization (WHO)
as one of the neglected diseases, is caused by parasites of the genus Leishmania
[17]. The WHO has attempted to control and eliminate leishmaniasis not only with
the development of effective ways of treatment, but, perhaps more importantly, by
prevention and control tools and programs. The list of actions taken is summarized
in the Global Vector Control Response 2017–2030 of WHO [18].
Leishmaniasis belongs to the parasitic, vector-borne group of diseases. The phlebotomine sandfly serves as the vector and more than 800 individual species of
such sandfly vectors have been identified to date. Only a small portion of them
(approximately 100 species) can transmit parasites pathogenic to humans [19, 20].
Leishmaniasis-related sandfly species are Lutzomyia, called “new world” species
(widespread in areas of Central and South America), and Phlebotomus, referred to
as “old world” species (widespread in areas of Europe, Asia, and Africa) [21]. In
terms of the development of leishmaniasis, the role of the sandfly vector is particularly important since the inner environment of the sandfly modulates the parasite’s
development and influences the final manifestation of the disease. Overall, the extent
of the disease manifestation results not only from the vector but also by variations in
the leishmanial parasite. To give a brief overview, linked below are different leishmanial species with the clinical manifestations of the illness and the area of occurrence
(Table 1) [22–24]. For this purpose, a simplified taxonomy of the Leishmania genus
has been employed that divides it into two main subgroups, Paraleishmania and
Euleishmania, which are further divided into the main subgenera, L. (Leishmania)
and L. (Viannia) [25]. The subgenus L. (Leishmania) relies on humans as the main
host reservoir, whereas in the case of L. (Viannia), humans are only an accidental
host [22–24].
From the life cycle viewpoint, leishmanial parasites are dimorphic organisms
inhabiting two different environments during their development. Within these two
periods, the parasite alternates between the promastigote and amastigote forms, with
the actual form determined by the environment. In the sandfly vector Phlebotomus
or Lutzomyia, the parasite lives in the form of promastigotes as a flagellated, extracellular organism, which needs to survive in conditions full of proteolytic enzymes
necessary for blood digestion [26–28]. After several specific interactions between
the sandfly gut and the parasite, the procyclic promastigotes are transformed into its
metacyclic form. The metacyclic form is covered with specific phosphoglycans that
gives the promastigote the necessary protection and also the means of interaction
(sandfly/parasite) [29–32]. In the metacyclic form, the parasite is motile, flagellated
and fully virulent due to the specific surface proteins (HASPs, SHERP or LPGlipophosphoglycans) [33–35]. During the time of procyclic/metacyclic transformation, the parasite migrates in the sandfly gut to the stomodeal valve. After reaching
this, the parasite destroys the stomodeal valve and causes a reflux of the parasite [36].
Consequently, when the sandfly is fed, the highly infective promastigote forms are