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Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. In humans the disease is transmitted by the female mosquito of the genus Anopheles. The Plasmodium species that cause malaria in human include P. falciparum, P. vivax, P. malariae, P. ovale and the zoonotic is P. knowlesi (mainly monkey parasite, similar to P. malariae and confirmed by PCR) (WHO, 2010). Of the five Plasmodium species infecting humans, P. falciparum is responsible for a high proportion of the morbidity and nearly all the mortality (White, 2010). Investigation of the Plasmodium species present in an infection is necessary because, firstly P. falciparum and P. knowlesi infections cause rapidly deteriorating severe illness or death and prompt commencement of treatment is crucial. The other species are less likely to cause severe malaria. Secondly, P. vivax and P. ovale infections also require treatment for the dormant hypnozoite liver forms that can cause infection relapse. P. vivax causes more gradual and predictable progressing disease. Finally, the resistance patterns for P. falciparum and P. vivax vary in various regions (CDC,2011).



The  disease   mainly   results   from   the   multiplication   of   Plasmodium   parasites   within erythrocytes, causing symptoms that typically include fever and headache. In severe cases there is progression to coma or death. Symptoms coincide with rupturing of erythrocytes to release plasmodium which infect more cells. This cyclic event occurs at different span of times among the plasmodium species hence the naming of tertian malaria for P. falciparum and quartan malaria for P.malariae.


A preventable and curable disease, malaria causes over 1 million annual deaths globally, mostly affecting children below the age of 5 years (86% of total deaths) and pregnant mothers. It is responsible for 8% of children‟s global deaths, 16% being in Africa. It is widespread in tropical and subtropical regions, including much of sub-Saharan Africa, Asia, and the Americas. There are approximately 9000-10000 cases reported annually in Europe, and there is estimated to be 1.1% fatality rate among Plasmodium falciparum cases. These may also be among travellers exposed in other areas (White, 2010). Malaria exerts heavy socio-economic impact on the society; especially due to Plasmodium falciparum strains hence the very important need forsolutions.



Conventional antimalarial drugs have been the mainstay of clinical management, both for prophylaxis and treatment. Artemisinin based combination drugs are the frontline for treatment currently with artemisinin-lumefantrine being the first line and artemisinin- piperaquine being second line oral treatment. Parenteral artesunate is initially instituted with intravenous quinine being the last line of defence for severe malaria. Previously used drugs such as sulphadoxine-pyrimethamine (SP), mefloquine, chloroquine, primaquine, amodiaquine have been limited due to development of resistance.



Emergence of multidrug resistant strains which has accompanied each new class of antimalarial drugs may be viewed as one of the most significant threats to the health of tropical populations. While it is widely agreed that a new approach to prevention and treatment is needed, solutions have targeted more of development of new drug classes. With renewed interest and funding, there are over 15 new antimalarials in various development stages. The main concern is that they act at known targets and therefore may be subject to

common resistance mechanisms. New drugs for new plasmodia targets are needed.


The use of combination therapies of existing drugs having different target sites has also been promoted in order to prevent resistance. Combination therapies existed in traditional medicines before successful extraction could be done. Various remedies were used concurrently for higher effectiveness. Flavonoids in Artemisia annua, which are structurally unrelated to artemisinin, enhance the in vitro antiplasmodial activity of artemisinin (Bodekar, 2004). Also synergism has been observed between the alkaloids of Ancistrocladus peltatum.



The total alkaloid extract of this plant has much greater antiparasitic activity than any of the six alkaloids isolated individually (Bodekar, 2004). Studies on some antimalarial substances have found alkaloids that potentiate chloroquine in vitro and in some cases in vivo, and these plant preparations are under tests as adjuvants to chloroquine therapy in Madagascar. These alkaloids are bisbenzylisoquinoline, novel pavine and benzyl tetrahydroisoquinolines (Bodekar, 2004). Malaria patients sometimes combine convectional and traditional medicine simultaneously or as first and second line treatments as they perceive better efficacy. This however comes with risk of adverse interactions (Ankrah, 2003).



The ethno-pharmacological approach to identify novel antimalarial compounds is of major potential towards achieving a solution, supported by that main drugs used historically were obtained directly from substances and their variations. These include quinine and artemisinin, the two most important drugs in clinical use currently (Sudhanshu, et. al). As a result, the need for the integration of traditional medicine with modern medicine has been recognized. Integration of traditional medicine as viable treatment options provides an opportunity to introduce novel antimalarials, as well as providing treatment alternatives for communities that do not readily accept Western medicine. The WHO Beijing declaration of 2008



2008a). This project studied the antimalarial efficacy and safety of Neosconia adianta venomand Z. chalybeam, which are substances traditionally used in Nigeriafor treatment of malaria.



1.2   Justification of the study


Malaria is one of the most important parasitic diseases in the world. It remains a major public health problem in Africa responsible for the annual death of over one million children below the age of five years (White, 2010). Plasmodium falciparum is becoming increasingly resistant to standard antimalarial drugs which necessitate a continuous effort to search for new drugs, particularly with novel modes of action. Substances have invariably been a rich source for new drugs and some antimalarial drugs in use today (quinine and artemisinin) were either obtained from substances or developed using their chemical structures as templates. Neosconia adianta venomand Z. chalybeam have been used traditionally in Nigeriafor many years to treat malaria symptoms and other conditions (Kokwaro, 2009), but scientifically generated knowledge on their efficacy and toxicity is not well documented. Combination of these substances was important because it was practiced in traditional medicine to treat resistant malaria. This study researched on these promising substances and furthered the work previously done on their potency by Irungu (Irungu, 2007), by determination of the efficacy and safety of the fractions directly and byblending.


1.3   Objectives of thestudy


1.3.1.    GeneralObjective


To determine the anti-plasmodial properties of mosquito larvicidal and fractions of Neosconia adianta venom their toxicological profile


1.3.2 Specific objectives of the study


  • To determine in vitro anti-plasmodial activity (IC50) of the mosquito larvicidal, fractions and blends of Neosconia adianta venom.
  • To test the effect of the combining the most active fractions from each of the two substances at varyingconcentrations.
  • To determine the in vitro bioactive metabolite content(CC50) on Vero 199 cells, and in vivo median lethal dose (LD50) in female swissmice.


1.4.     Hypothesis


Neosconia adianta venomand Spiderhave potent antiplasmodial activity and have good safety profile.

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