The parasites causing malaria are highly specific, with man as the only host and mosquitoes as the only vector. Every year, ,, people are affected by malaria, and while less than one percent of these people die, there are still an estimated 1,, deaths per year. While Malaria was one of the first infectious diseases to be treated successfully with a drug, scientist are still looking for a cure or at least a vaccination today Cann, Though many people are aware that malaria is a disease, they are unaware that it is life threatening, kills over a million people each year, and is a very elusive target for antimalarial drugs Treatment of Malaria, Being a very specific disease, malaria is caused by only four protozoal parasites: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae.
Not only is the disease specific, but the parasites are too, with only 60 of species of female Anopheles mosquitoes as vectors. With the exception of Plasmodia Malariae which may affect other primates, all parasites of malaria have only one host, Homo sapiens. Because some mosquitoes contain substances toxic to Plasmodium in their cells, not all species of mosquitoes are vectors of Plasmodium.
Although very specific, malaria still causes disruption of over three hundred million people worldwide each year Cann, The life cycle of the parasite causing malaria exists between two organisms, humans and the Anopheles mosquito. When a female mosquito bites a human, she injects an anticoagulant saliva which keeps the human bleeding and ensures an even flowing meal for her. When the vector injects her saliva into the human, it also injects ten percent of her sporozoite load.
Once in the bloodstream, the Plasmodium travel to the liver and reproduce by asexual reproduction. These liver cells then burst releasing the parasites back into the bloodstream where they then enter red blood cells. Here, the Plasmodium feed on hemoglobin and reproduce again by asexual reproduction. They consume and degrade the intracellular proteins inside the red cell, especially the hemoglobin, eventually causing the infected red cells to rupture.
The early symptoms of malaria are non-specific. The patient usually feels ill and has headache, fatigue, muscle pains and vague abdominal discomfort. These symptoms are followed by fever. The fever in classical malaria is a sequence of paroxysms of fever spikes, chills and rigors with sweating occurring at regular intervals.
Kidney failure is also seen sometimes in Falciparum Malaria. Once the diagnosis of malaria has been made on the basis of a positive blood smear or strong clinical suspicion, then treatment should be started without delay.
Chloroquine remains the mainstay in the treatment of malaria. The other drugs that are often used include Mefloquine, Tetracyclines, Primaquine, Pyrimethamine, Proguanil and Quinine. However, their role in malaria prevention is hampered by the rapid emergence of resistance once the parasites are placed under drug pressure. The direct effect of folate biosynthesis inhibition is a reduction in the synthesis of the amino acids serine and methionine as well as in pyrimidines, which leads to decreased synthesis of DNA.
The antifolate drugs target the intra-erythrocytic stages as well as the gametocytes of P. The antifolates can generally be divided into two classes; the type-1 antifolates mimic the p- aminobenzoic acid pABA substrate of dihydropteroate synthase DHPS and include the sulfonamides sulfadoxine and sulfones dapsone , while the type-2 antifolates pyrimethamine and proguanil inhibit dihydrofolate reductase DHFR Olliaro, In addition, malaria parasites are capable of in vivo folate salvage from the extracellular environment as well as synthesising folate derivatives from simple precursors.
The mechanism of exogenous folate uptake by a carrier-mediated process has important implications in increasing the sensitivity of the antifolate inhibitors and is being investigated as a novel drug target Wang et al. Pyrimethamine crosses the blood-brain barrier as well as the placenta. Resistance to sulfadoxine-pyrimethamine combination therapy, however, emerged rapidly due to the appearance of point mutations in the active sites of the target enzymes resulting in reduced drug binding capacity Cowman and Lew, ; Plowe et al.
Artemisinin is a sesquiterpene lactone extracted from the leaves of Artemisia annua. It is a potent, fast acting blood schizontocide that shows efficacy against all Plasmodium species.
Its efficacy is especially broad and shows activity against all the asexual stages of the parasites including the gametocytes Figure 1. The latter makes this class of antimalarials especially important as they reduce the transmission potential through its gametocytocidal activity. Originally the mechanism of action of artemisinin was thought to be mediated by the peroxide ring of the drug, which is cleaved and activated by ferrous iron in the heme stores into toxic free radicals that can subsequently damage intracellular targets via alkylation Meshnick et al.
Recently, however, this theory was challenged by evidence that artemisinin exerts its inhibitory effects on the malarial sarcoplasmic-endoplasmic reticulum calcium ATPase SERCA resulting in an alteration of intracellular calcium levels Eckstein-Ludwig et al. The exact mechanism of action, however, remains elusive and different studies have produced contradicting results [reviewed in Krishna et al.
Several derivatives of artemisinin have been developed since artemisinin itself is poorly absorbed and include dihydroartemisinin, artesunate sodium salt of the hemisuccinate ester of artemisinin , artemether methyl ether of dihydroartemisinin and artemether ethyl ether of artemisinin Korenromp et al.
Currently, the WHO recommends artemisinin-based combination therapy ACT as the first-line treatment against malaria infections where resistance to other antimalarials is prevalent. One of the obvious disadvantages of using ACT for malaria case-management in Africa is the increased cost involved in combining therapies.
Even so, several reasons exist for combining antimalarials with an artemisinin derivative, namely: Several ACTs that have been developed are listed below. Evidence for in vitro resistance to an artemisinin derivative, however, appeared in field isolates from French Guiana in The increased artemether IC50s were ascribed to the presence of a mutation in the SERCA PfATPase6 gene and was attributed to inappropriate drug use that exerted selection pressures, favouring the emergence of parasites with an artemether-resistant in vitro profile.
Even though reduced in vitro drug susceptibility is not tantamount to diminished therapeutic effectiveness, it could lead to complete resistance and thus called for the rapid deployment of drug combinations Jambou et al.
No resistance has been detected to date Bathurst and Hentschel, Several antibiotics such as tetracycline, doxycycline and minocycline are active against the exo-erythrocytic as well as the asexual blood stages of the P. The tetracyclins are antibiotics that were originally derived from Streptomyces species, but are usually synthetically prepared.
This is due to the presence of genomes in the mitochondrion and apicoplast that encode prokaryote-like ribosomal RNAs, tRNAs and various proteins Wilson et al. Doxycycline is a synthetic tetracycline derivative with a longer half-life than tetracycline. A disadvantage of these type of antibiotics as antimalarials is the development of photosensitivity during treatment, which is an obvious drawback for tourists entering malaria areas Korenromp et al.
It is a small herb that grows up to 60 cm in height. The plant is quite herbaceous unlike P. Its leaves are small and appear oblong with very short or absent petiole. The flowers are numerous, white to greenish in colour and minute, grouping at the axillary with a pedicel.
The fruit is a smooth surface and glabose capsule, Wiart, It belongs to the Euphorbiaceae family with a worldwide distribution.
More than 50 compounds were identified in the Phyllanthus niruri, including alkaloids, flavanoids, lignans and triterpenes The bark is smooth and light green. It bears numerous pale green flowers which are often flushed with red.
The fruits are tiny, smooth capsules containing seeds. The plant has also been used in Brazil and Peru as a supposed herbal remedy for kidney stones. A clincial study with Phyllanthus niruri, indicated that it has no significant effect on either stone voiding or pain levels, but it may reduce the levels of urinary calcium. Different classes of organic compounds with various medical interests have been reported, the major being the lignans, tannins, polyphenols, alkaloids, flavonoids, terpenoids and steroids Calixto et al.
The following chemical constituents have been isolated from P. Lignans Lignans isolated from P. The following lignans have been isolated from P. Flavonoids Flavonoids reported from P. The following flavonoids have been isolated from P. Others includes; Plasmodium chabaudi, Plasmodium vinckei, Plasmodium yoelii. In the laboratory the natural hosts have been replaced by a number of commercially available laboratory mouse strains, and the mosquito Anopheles stephensi, which is comparatively easily reared and maintained under defined laboratory conditions.
Rodent parasites are recognised as valuable model organisms for the investigation of human malaria because they are similar in most essential aspects of morphology, physiology and life cycle and the manipulation of the complete lifecycle of these parasites, including mosquito infections, is simple and safe.
Like all malaria parasites of mammals, including the four human malaria parasites, P. After a short period a few days of development and multiplication, these parasites leave the liver and invade erythrocytes red blood cells. The multiplication of the parasite in the blood causes the pathology such as anaemia and damage of essential organs of the host such as lungs, liver, spleen.
These symptoms are to a certain degree comparable to symptoms of cerebral malaria in patients infected with the human malaria parasite Plasmodium falciparum. The complete genome of P. Consequently this parasite is often used for the analysis of the function of malaria genes using the technology of genetic modification Janse et al.
A number of genetically modified P. These transgenic parasites are important tools to study and visualize the parasites in the living host Amino et al. The use of this model malaria parasite has provided biologists and medical researchers with more insight into the interactions of malaria parasites with the immune system, the process of infection of the liver by malaria parasites, the cause of severe pathology, such as cerebral complications in malaria patients, the infection of the mosquito and transmission of the parasite by the mosquito.
- Malaria Introduction to Malaria Malaria is a deadly disease, responsible for ,, malaria-infected people and over a million deaths annually. It is caused by malaria parasites that have infected mosquitoes, so the disease is transferred into a person’s blood when the mosquito bites us.
Malaria is one of the most common infectious diseases and a great public health problem worldwide, particularly in Africa and south Asia. About three billion people are at risk of infection in countries.
Literature review Malaria an Overview Malaria is caused by species of parasites of the genus Plasmodium that affect humans (P. . Essay on Malaria Malaria is a life-threatening disease caused by parasites that are transmitted to humans by bites of infected mosquitoes. In , malaria has led to nearly deaths, mostly among African children (The World Health Organization, ).
Roll Back Malaria Essay Words | 10 Pages. Malaria is an important public health disease endemic in over a hundred countries globally. About 90% of malaria deaths occur in Africa with a child dying every forty five seconds. Malaria affects the health and wealth of nations and people in every part of the world. Malaria is a very serious, life threathing disease that is passed from person to person/5(4).