2.1.7.2 Drugs in the Pipeline
The development of strains resistant
to commonly used drugs and lack of affordable new drugs are the limiting
aspects in the fight against malaria. These factors trigger the
continuing need of research for new classes of antimalarial agents, and a
re-examination of the existing antimalarial drugs. Hence, dantrolene
(Kang et al., 2005), antiadhesion adjunctive therapies like levamisole
(Rowe et al., 2009), acriflavine (Dana et al., 2014) and acridiones such
as WR249685 and T3.5 (Beteck et al., 2014) are under investigation.
P218, 21A092 and others are also in preclinical studies (Bvgh, 2015).
The study done by Danny et al. (2015) identified for the first time that
macrolide antibiotics inhibit Plasmodium species merozoite invasion in
to erythrocytes in vitro.
A wonderful drug (named ddd107498) for
malaria treatment and control has recently been developed in India and
about to enter human clinical trial (Das and Dash, 2016). SJ733 14 was
tested successfully in preclinical studies (Medical Xpress, 2016) and
now in human trial (St. Jude Children’s Research Hospital, 2016).
MMV39048 has finished phase I trial (Chibale, 2016). Moreover, CDRI
97/78, ACT451840, Sevuparin and GSK369796 are among drugs under phase I
trial (Marco et al., 2013; Janet et al., 2016).
The new
organometallic drug ferroquine (SR97193) is undergoing Phase II clinical
trial as combination therapy with artesunate [Anna et al., 2012].
Novartis currently has two new classes of antimalarial drug in Phase II
clinical testing: KAE609 (Cipargamin) and KAF156. They have the
potential to treat malaria and block transmission (Novartis, 2014).
Ozonides are proved to be useful substitutes for artemisinin. The
first-generation OZ277 was developed and subsequently called arterolane.
After a limited Phase III programme, the combination of arterolane and
piperaquine has got approval under the trade name Synriam in India in
2013. The second-generation OZ439 (artefenomel) is now in Phase IIa
studies [Reddy et al, 2013] and also being tested in a Phase IIb
combination trial with piperaquine, and is about to be tested in another
with ferroquine (Janet et al., 2016).
A second-generation
artemisinin derivative, artemisone, a drug in Phase II trial, provides a
single-dose cure when combined with mefloquine (Phillips et al., 2015).
Fosmidomycin is under combination therapy trial with piperaquine in
phase II (Bvgh, 2015). AQ-13 (a modified chloroquine) and DSM265 are
other compounds in phase II (Martin, 2008; Bvgh, 2015; Janet et al.,
2016). Multiple novel combination therapies, including
azithromycin-chloroquine (Chandra et al. 2013), pediatric
pyronaridine-artesunate, pediatric dihydroartemisin in piperaquine
(Bvgh, 2015) and trimethoprim-sulfamethoxazole (Janet et al., 2016) are
in phase III trial. The primaquine analog tafenoquine is has recently
shown great promise in Phase II trial and is currently being tested in
pivotal Phase III trial and has proven activity against hypnozoites
(Rajapakse et al., 2015).
2.2 Traditional Medicine
Traditional
medicine (TM) use varies among countries depending on a number of
factors. In Singapore and the Republic of Korea where the conventional
health-care system is quite well established, 76% and 86% of the
respective populations still commonly use TMs. About 90% of general
hospitals provide TM services for both outpatients and inpatients in
China. Over 100 million Europeans are TM users (WHO, 2013). In
developing countries, 80% of the people almost exclusively use TMs.
Virtually, 80% of the population living in Ethiopia is dependent on
traditional medicine which essentially involves the use of plants (Agbor
et al., 2011; Asmare and Kesara, 2015).
More than 1,200 plants that
possess antimalarial activities are reported worldwide (Rasoanaivo et
al., 2011). It is probable that some of them contain as yet undiscovered
active constituents. For example, Ampelozyziphus amazonicus and
Strychnopsis thouarsii were commonly used in malaria-endemic areas of
Brazil and Madagascar, and their anti-sporozoite activities have been
demonstrated (Anna et al., 2012).
Ethiopia is rich in a wide range
of tropical habitats, remarkable biodiversity and use of traditional
remedies for the treatment of various ailments (Deressa et al., 2010).
Studies conducted on several traditionally claimed Ethiopian medicinal
plants, such as: Calpurnia aurea (Mebrahtu et al., 2013), Croton
macrostachyus (Bantie et al., 2014), Asparagus africanus (Yared et al.,
2012), Withania somnifera (Dikasso et al., 2006), Dodonaea angustifolia
(Mengiste et al., 2012) and Phytolacca dodecandra (Mequanint, 2014),
confirmed their antimalarial activities.
