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ANTIHYPERLIPIDEMIA AGENTS Plasma lipids Transported in bloodstream in form of macromolecular complexes of lipid and known as lipoproteins Two major clinical importance/sequelae of high lipid Acute pancreatitis atherosclerosis Hyperlipoproteinemia Hyperlipidemia Lipoprotein disorders Primary hypertriglyceridemias Primary chylomicronemia Familial hypertriglyceridemia Familial combined hyperlipoproteinemia Familial dysbetalipoproteinemia Primary hypercholesterolemias Famimial hypercholesterolemia Familial ligan-defective apolipoprotein B Familial combine hyperlipoproteinemia Lp(a) hyperlipoproteinemia Secondary hyperlipoproteinemia Lipid-lowering drugs Several drugs are used To decrease plasma LDL-cholesterol Drug therapy is only one approach Dietary measures are the first [...] | 19th January, 2010 | More News
Malaria-vaccines
Introduction to Malaria
Malaria is a life-threatening parasitic disease transmitted by mosquitoes known as anopheles. The disease has been described in 3000 years old documents from China and India. It was once thought that the disease has long associates of ‘evil spirit’ with ‘night air’, hence the name malaria, mal = bad and aria = air. Scientists and researchers play an important role in identified this disease since long time ago. As early as in 1880, scientists discovered the real cause of malaria that was a unicellular parasite called Plasmodium. Later they discovered that the parasite was transmitted from person to person through the bite of a female Anopheles mosquito, which requires blood to nurture her eggs1. Human malaria is caused by four species of the protozoan Plasmodium: P. falciparum, P.vivax, P. ovale, and P. malariae. The life cycle and parasite-host interaction of each species determines the severity, pathogenesis, chronicity and chronology of clinical disease.
Current status of Malaria
Malaria, HIV/AIDS and tuberculosis, are the major public health challenges undermining development in the poorest countries in the world. Malaria remains the world’s most notorious tropical parasitic disease, threatening some 2,400 million people, 40% of the world population. According to the World Health Organization (WHO), there are an estimated 300-500 million new cases of malaria each year and over one million deaths, most of whom are African children2.
Malaria vaccine versus other control measures
Even though some countries have showed the effectiveness of the malaria control by environmental changes and changes in agricultural practices such as in Europe and the United States but these does not happen in others developing and least developed country where malaria is endemic and hyperendemic. Other tools of prevention, such as insecticide treated bednets (ITNs) and intermittent preventive treatment in infants (IPTi), are available and widely used in those countries. It seems that it is more cost effective than malaria vaccines3. The WHO Roll Back Malaria programme is coordinating improved case management, insecticide-treated bednets, and other control measures for reduction of malaria mortality. Malaria drug development is a research priority4. Researchers still believe that vaccination is the best way to control and eradicate the disease.
Emergence of drug-resistant strains of malaria parasites
The main problems with the existent malaria chemotherapies are the increasing resistant of malaria parasite towards malaria drug. To proof this, extensive research revealed that resistance to chloroquine occurs via an active energy-dependent process of efflux of chloroquine from the P. falciparum parasite cells5. Infection with chloroquine-resistant P. falciparum and its spread occurs either by local transmission and migration of reservoirs (primary resistance), or through selection of resistant parasites because of exposure to sublethal drug concentrations (secondary resistance). The latter mechanism is responsible for the majority of new cases in areas not known to be chloroquine-resistant.
Malaria vaccine candidate and development
Researchers and scientists from all over the world are actively involves in the development of malaria vaccines despite of failure to produce a potent vaccine. Different approaches and techniques have been tried, and as the result the researches have found several candidates for vaccine developments. Examples of the approaches are reverse immunogenetics, reverse vaccinology6, DNA vaccines, conventional subunit, etc. A number of malaria vaccine candidates have been tested in clinical trials and have demonstrated variable safety and immunogenicity.
Generally, researchers have divided the malaria vaccines into three groups that are a) Pre-Erythrocytic Vaccines, b) Blood-stage vaccines, and c) Transmission-Blocking vaccines.
a) The Pre-Erythrocytic Vaccines strategies are targeting the sporozoite aim to generate a humoral immune against the sporozoite and prevent it from invading the hepatocyte. It is focused on the circumsporozoite protein (CSP) that is a major surface protein of the sporozoite. The properties for this stage vaccine are able to induce high titres of functional antibodies against sporozoites to prevent all parasites entering the liver stage, and induce potent cytotoxic T-lymphocyte immunogenicity against the liver stage to kill infected hepatocytes, while not harming the human host. For example, Hepatitis B surface antigen DNA was fused to DNA encoding a large part of the pre-erythrocytic malaria antigen, the circumsporozoite (CS) protein.
b) The Blood-Stage Vaccines are considered an antibody-dependent vaccination by the researchers. It acts either by inactivating the merozoites in the extracellular or by targeting malarial antigens expressed on the red blood cell surface to antibody-dependent cellular inhibition. Merozoite surface protein-1 is the most well characterized antigen involved in invasion, and is the basis of several candidate vaccines. The PfEMP-1 which expressed on the surface of infected erythrocytes is being used as a vaccine candidate by several researchers. Others vaccines of this categories are SPf66 vaccine, RTS,S vaccine and Combination B vaccine.
c) The Transmission-blocking vaccines rely on the mosquito imbibling both antibody and complement along with the parasite during a blood meal. Within the mosquito, the antigens become exposed to antibodies during the parasite’s maturation, thus neutralizing the sexual stages. This vaccines will prevents further spread of malaria by mosquitoes feeding from the vaccinated host. It is suitable in area of low endemicity to halt transmission or as important component of a multiantigen vaccine2.
Subunit vaccines
In subunit vaccines, the researchers have identified that part or complete antigens from a pathogen’s proteomic complement, which can induce protective immunity to the whole pathogen. Because of the subunit vaccine does not sufficiently produces immune response, researchers have developed a recombinant protein subunit vaccines. The newest generation of subunit vaccines are DNA based which can induce high levels of effector T-cell immune responses. Both DNA and recombinant viral vaccines work in a similar way i.e these vaccines are taken up by host cells, protein is expressed, and T-cells epitopes bound to HLA molecules prime naïve T cells to form memory T-cell populations. The difference of that DNA vaccine is the recombinant viral vaccine actively infect cells and express the recombinant malaria proteins before aborting infection.
This wide range of choices clearly increases the chance of success, but each approach has its problems, for example, extensive antigenic variation in the blood stage, and the need for 100 percent efficacy with the hepatic and prehepatic stage, also the sexual stage vaccines would only block transmission, protecting the community but not the vaccine. Each approach has its vigorous proponents, but it seems likely that a successful vaccine will contain antigen from several or all stages. Sooner or later, from the various works of the researchers, hopefully a potent malaria vaccine will become a reality.
References
1. Richard L. Guerrant, David H. Walker, Peter F. Weller. Tropical Infectious Diseases, 2nd Edition,2006. Stephen L. Hoffman, Carlos C. Campbell, Nicholas J. White. Malaria Chapter 90: 1024-1062
2. Plotkin, Orenstein. Vaccines fourth edition 2004. Filip Dubovsky, N. Regina Rabinovich, Chapter 47 Malaria vaccines: 1283 – 1287.
3. Brian Greenwood, Malaria vaccines Evaluation and implementation. Acta Tropica 95 (2005) 298-304
4. Vasee S Moorthy, Michael F Good, Adrian V S Hill. Malaria vaccine developments. Lancet 2004: 363: 150-56
5. Krogstad D. J. and Gluzman I. Y. Efflux of chloroquine from Plasmodium falciparum mechanism of chloroquine resistance. 1987. science, 238(5): 1283-1285.
6. L.J.M. Carvalho, C.T. Daniel-Ribeiro, H. Goto. Malaria Vaccine: Candidate Antigens, Mechanisms, Constraints and Prospects. Scand. J. Immunol. 56, 327-343, 2002
About the Author
Specialized in Tropical Medicine and Research on men health especially in osteoporosis
bagus
Malaria vaccine development can be done with extensive research and development