Microbes Responsible for Malaria - Research Paper Example

Sur Supervisor Malaria Malaria has been a major cause of global morbidity and mortality and it spreads mostly during rainy season. Humans get affected due to anopheline mosquitos. The gut of mosquito is the place where malaria protozoa develop. When mosquito sucks blood from the human body, the protozoa enters human body. Due to the process of blood circulation, the parasite reaches to the liver of the person where it multiplies. It takes usually 9-16 days before it penetrates red blood cells causing them to breakdown. The paper attempts to explore the type of microbes that cause malaria; symptoms of malaria; the system it affects and the cellular and molecular mechanism of malaria along with the key proteins involved in this process. The paper also aims at exploring the efficacy of drugs for the treatment of various forms of malaria and the challenges ahead due to drug resistance developed by malarial parasites. Microbes Responsible for Malaria As such many microbes are responsible causing malaria; however, the important ones are plasmodium vivax and plasmodium falciparum causing malaria in most part of the world (World Malaria Report). Symptoms of Malaria Usual symptoms of malaria are shivering, fever, vomiting and headache and likely to appear only after a week or two after the mosquito bite. In case of cerebral malaria, clinical symptoms resemble considerably to the symptoms that arise from meningitis and pneumonia and therefore malaria microscopy cannot help there much as a diagnostic tool for clinical management. If not treated in time, malarial parasites can cause death as it disintegrates red cells and disrupts supply of blood to the major organs of the body (World Health Organization). Cellular and Molecular Biology of Plasmodium At cellular level plasmodium performs two major actions. Erythrocyte invasion is the first action that plasmodium finishes at the cellular level. After invasion it modifies erythrocytes to make them fit for habitat (Wiser). Plasmodium is known to have three invasive forms such as merozoite, ookinete and sporozoite. It will be worth pondering on the erythrocyte invasion of merozoites. Merozoites take no time to enter erythrocytes because erythrocyte is the preferred host cell type. The invasion is a complicated process but it passes through four steps and that can be described as Merozoite binding; Erythrocyte deformation and reorientation; Junction formation and parasite entry (Wiser). Though several merozoite surface proteins participate in the action, merozoite surface protein-1 (MSP-1) is the prominent of all. Moreover, the circumsporozoite protein (CSP) also participates in the whole process of targeting sporozoites. After binding to the erythrocyte is complete, the 'apical end of the parasite' gets aligned with erythrocyte membrane. This also results into erythrocyte deformation. Apical membrane antigen-1 (AMA-1) is involved in the realignment process. Specialized apical organelles called micronemes, rhoptries, and dense granules are involved in the invasive process of parasites. With the invasion of parasite, the apical organelles are spewed out indicating that organelles do play some role in invasion. It has been established that micronemes are spewed out as the contact between the parasite and host takes place. The rhoptries are discharged after the micronemes. Once the parasite completes its entry, dense granules are released modifying the host cell (Wiser). Specific Interactions and Junction Formation Formation of junction, between the parasite and host cell, takes place once microneme discharge is complete. That means microneme proteins play important role in junction formation (Wiser). Key Proteins Involved in the Process a) Duffy-binding protein (DBP) from P. vivax; b) A 175 kDa 'erythrocyte binding antigen' (EBA-175) from P. falciparum; c) Plasmodium sporozoite surface protein-2 (SSP2). It is also called TRAP (thrombospondin-related adhesive protein). The parasite undergoes metamorphosis when it enters erythrocyte. During this time, the parasite makes certain changes within the host such as making the membrane more permeable to live and grow there (Wiser). Summarizing Invasive Mechanism The mechanism of parasite invasion can be summarized in the following lines: Merozoite binding takes place due to interaction between host erythrocyte and surface proteins. This is followed by reorientation at the apical end of the merozoite getting aligned with erythrocyte membrane. Formation of a tight junction between the host and parasite takes place once the discharge of microneme is complete (Wiser). Modifying Erythrocyte With the invasion process over, malarial parasites tend to modify the erythrocytes by transmitting proteins into it. Polymorphic proteins known as PfEMP1, believed to function as a ligand, appear on the erythrocyte surface binding with the receptors on host cells. This promotes sequestration and maneuvers the infected erythrocyte to avoid the spleen. Thus, antigenically distinct PfEMP1 molecules found on the erythrocyte surface is ready to combat the host immune response successfully (Wiser). Cerebral Malaria Cerebral malaria occurs when red blood cells block the pathway in the brain stopping the blood flow depriving oxygen and nutrients necessary for the brain. Small vessels do not get necessary blood supply throughout the brain. Usually, one-half of the patients suffering from cerebral malaria are found to have seizures and increased intracranial pressures. The patient with cerebral malaria will have an abnormal EEG due to reduced levels of oxygen. Also, MRI of the patient will display infarction and hemorrhagic lesions if affected by the cerebral malaria. If left untreated for a long period, this may result into fatal brain stem herniation; however, those who survive are not found with any residual neurological issues. Only around 10 percent of the patients are found to have a long term neurological deficiencies such as spasticity, hypotonia or hemiparesis (Davidson). Malaria Diagnosis and Treatment World Malaria Report 2010 has recommended a parasitological confirmation of diagnosis to be completed by either rapid diagnostic test (RDT) method or microscopy. Currently, the use of RDT has increased considerably from around 200,000 in 2005 to almost 30 million during 2009. Microscopic examination has been reducing in most parts of the world including regions of the Americas and Europe (World Malaria Report 25). World Health Organization guidelines for treatment of Malaria can be described as per the following (World Malaria Report 5). 1. Rapid diagnostic tests (RDTs) or parasitological confirmation by microscopy has been recommended in suspected malaria cases before treatment process is started. 2. Artemisinin-based combination therapy (ACT) is necessary to treat uncomplicated P. falciparum malaria. A single dose of primaquine medicine is also suggested along with ACTs for treatment of P. falciparum malaria. 3. The five choices of ACTs are artesunate plus amodiaquine, artemether plus lumefantrine, artesunate plus sulfadoxine-pyrimethamine (SP), artesunate plus mefloquine, and dihydroartemisinin plus piperaquine. The choice of the ACT depends on the country and region keeping in mind the efficacy and the resistance to the drugs. 4. Oral monotherapies using artemisinin and its derivatives are to be avoided to prevent development of resistance to this valuable class of antimalarials. Treatment of P. vivax Malaria As per World Malaria Report 2010, Chloroquine still remains the first line of treatment in the regions where no severe resistance to the drug has been noticed. Though some regions have noticed spread of some degree of chloroquine-resistant P. vivax yet its severity cannot be established. In those areas where resistance to chloroquine has been noticed, ACTs have been a drug of choice for the treatment of chloroquine-resistant P. vivax (36). The numbers using ACT treatments are increasing every year. In 2009, it has reached to 158 million. The use of artemether-lumefantrine (AL) constitutes major portion of artemisinin-based combination therapy (ACT) – accounting for almost 67 percent in 2009. The use of artesunate + amodiaquine based ACT comes next which has reached to 23.2 million cases in 2009 from only 1 million treatment courses in 2007 (28). Understanding Anti-malarial Drug Resistance and Challenges Ahead P. falciparum drug resistance has been a major challenge for medical practitioners now. Different drugs show varied levels of efficacy in the different parts of the world. Some of the observations are as per the following (World Malaria Report 34). 1. Artemethr-lumefantrine is usually found to be effective in most parts of the world except Cambodia. 2. Artesunate-mefloquine is not effective where parasites have developed resistance to mefloquine such as Greater Mekong region; however, so far it has been found effective in Africa and the Americas. 3. The effectiveness of artesunate-amodiaquine is questionable in some of the African countries including Indonesia. 4. Many countries have developed resistance to artesunate-sulfadoxine-pyrimethamine and the drug is now not used as first line of treatment. To prevent spread of malaria has been a challenging task especially in the tropical regions of the world. Efficacy of drug is extremely important to prevent parasites developing a drug resistance. Though efficacy of ACTs in treatment process has not yet been compromised; nevertheless, both components of the drug are at risk. If one of the partner medicines is ineffective, it increases the risk of resistance for other combination drug. For this reason only, World Health Organization decided to withdraw oral artemisinin-based monotherapies so as to prevent long-term resistance to the drug. World Malaria Report speaks about achieving zero death due to malaria by 2015 (3). It is commendable that eleven African countries in collaboration with international partners have been successful in reducing the malaria cases and deaths by 50 percent saving millions of lives across the continent. As a preventive measure, insecticide-treated mosquito nets have been delivered protecting 580 million people. Moreover, more than 75 million people have been given protection through indoor spraying of the insecticides. More and more countries are getting out of the grip of malaria. In past, fever has been mostly associated with malaria in many parts of the world but it is no longer so due to concerted efforts collectively put by so many public and private agencies. Works-Cited Davidson. “What is Cerebral Malaria?” davidson.edu. Web. 2 Dec. 2012. . Wiser, Mark. “Cellular and Molecular Biology of Plasmodium.” Tulane University.2011. Web. 2 Dec. 2012. . World Health Organization. “Malaria”. Web. 2 Dec. 2012. . “World Malaria Report 2010”. World Health Organization. 2010. Web. 2 Dec. 2012. . Read More