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Malaria By: Keith Klain Tracy Tomich Jasmine Ferrell Jesse Trigg You've just been bit by a female anopheles mosquito (a type of mosquito which carries one of the four types of Plasmodium, which cause malaria). Plasmodium from any one of the following four species can cause malaria: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. Though all four of these species cause malaria, some differences exist in their life cycles which will be addressed when appropriate. The four plasmodium are eukaryotic (possess at least one cell with a clearly defined nucleus), protozoan (a group which is usually microscopic, and in this case is parasitic), and unicellular (tulane). The plasmodiums are introduced into the bloodstream of a human via the bite of a mosquito. Once in the bloodstream the parasite is referred to as a sporozoite. The sporozoite travels to the liver within 1 hour. Once in a liver cell, the sporozoite asexually reproduces. The sporozoite divides its nucleus, but not its cytoplasm (nuclear division) several times until the liver cell ruptures. The numerous nuclear divisions are referred to as merozoites (tulane). The merozoites are then released into the blood's circulation. The merozoite's goal while in the bloodstream is to attack as many Red Blood Cells (RBC) as possible and infect them in a similiar fashion as in the liver cell. The merozoite hunts the RBC's and detects surface proteins then invades it. After the invasion of the RBC, scientists refer to this as the trophic period, a time marked by enlargement of the merozoite and the consuming of the RBC's cytoplasm. During the trophic period the parasite takes on a ring shape. During this trophic period the merozoite is called a trophozoite. The trophozoite also breaks down the RBC's hemoglobin into consumable amino acids, which are the building blocks of proteins (tulane). Once the trophozoite initiates nuclear division, experts term this the schizont stage. After 3-5 rounds of replication the RBC ruptures and the merozoites are released into the bloodstream to infect new RBC's. The rupturing of the RBC's simultaneously, sub sequential releasing of antigens, and the release of waste products are why humans respond with intermittent fevers (tulane). Most of the merozoites and trophozoites move from RBC to RBC however, there is another path that a smaller percentage of the parasites follow. This small percentage will change into sexually reproductive parasites. These parasites are called micro or macrogametocytes. They wait in the bloodstream, instead of seeking out another RBC to infect. Once a mosquito ingests them, the microgametocyte is able to detect temperature, carbon dioxide levels, and pH fluctuations which are important to decipher when it has exited the human host. The macrogameteocytes or microgameteocytes have another survival mechanism: once blood is exposed to air, the parasite automatically sprouts flagella which provide motility. The microgameteocyte's mission is to find a mate in order to create of a zygote (tulane). The zygote will develop into an ookinete. The ookinete burrows it's way out of the mosquitoes gut and during this traveling period is transformed into what is called an oocyst. The oocyst performs asexual reproduction sends the result of this reproduction (called sporozoites) into the mosquito’s bloodstream. Sporozoites are designed to seek out the mosquitoe's salivary glands. Once in the salivary glands the sporozoites are prepared to hitch a ride into a new host's bloodstream (CDC). The malarial parasites have some differences depending on the specific Plasmodium. For instance, regarding the P. vivax and P. ovale the parasite invades the liver cells but may enter a dormant phase appropriately referred to as a hypnozoite. Hypnozoites are responsible for the relapse of malaria, for they can reactivate and cause malarial fevers months or even years later (CDC). Malaria has plagued man as long as man has walked the earth. Fossil records show evidence of the malaria causing parasites existence within mosquitoes up to 30 million years ago. The disease probably originated in Africa (where man probably originated as well) (Nobel Prize). There are writings from as far back as 2700 years B.C. In these writings are the symptoms noted in the Chinese canon of medicine (CDC). In the 4th century B.C. a doctor by the name of Hippocrates from ancient Greece was the first individual to describe the most proliferate season for the spread, the most relevant geographical regions, and the symptoms of Malaria (scarab). In the 2nd century B.C. the Chinese recorded an anti-fever remedy (translated into English) called sweet wormwood. In 1971 Chinese scientists isolated the single ingredient responsible for the medicinal properties associated with the wormwood. To this day this ingredient is used effectively when combined with other medicines (CDC). In 1600 the first treatment of bitter bark from the Peruvian Cinchona tree was used. This same source is known and used as Quinine (CDC). During the civil war from which started in 1861 and ended in1865, 10,000 people from the Union army died due to malaria (scarab). 15 years later in Algeria a man by the name of Alphonre Laveran discovered the parasite responsible for malaria in human blood. 17 years after Alphonre, in the same country, Ronald Ross discovered the link between mosquitoes and the parasite, in relationship to the disease (CDC). In 1899 Giovanni Batista Grassi and a team of Italian investigators completed the rationale behind the sporogonic cycle of the four different Plasmodiums. This group of people accomplished this by controlling conditions. Such conditions included: the orchestrated feeding of malaria infected human blood by a non malaria infected mosquito to prove the sporogonic cycle did in fact exist. Discoveries like Mr. Grassi’s helped people achieve major endeavors such as the creation of the Panama Canal. Without research like Mr. Grassi’s the Panama Canal would have taken longer and would have cost more lives due to malaria and yellow fever (CDC). Politicians like Franklin Roosevelt have contributed to the demise of malaria. In 1933 Roosevelt signed a bill called the Integration of Malaria control with economic development. There are 2 main reasons this bill helped to eradicate malaria within the Tennessee valley area and the U.S. First, the mosquito’s breeding sites were downsized because the water levels were more controlled. Secondly, insecticide applications were started. In 1947 the disease was virtually done away with in the Tennessee Valley. In 1951 Malaria was considered eradicated in the U.S. This was made possible by people like Roosevelt and by chemicals such as house spray applications which are designed to deter mosquitoes (CDC). In 1955 the World Health Organization proposed to eradicate Malaria worldwide. Due to wars, lack of stable financial commitments to impoverished nations, resistant strains emerging in response to the latest drugs, and the sheer magnitude of the problem in sub-Saharan Africa, the project was re-evaluated. After the re-evaluation in 1978, the project was downgraded to a realistic approach of controlling the disease (CDC). Malaria is prevalent in the tropics and subtropics. Places such as Africa, Thailand, South America, Mexico, and India, are some of the most infected areas on earth (traveldoctor.co.uk, 2005). 300 to 500 million people are currently infected with this disease (Webster, 2003). The rates of mortality are said to be between one and three million people each year (shands.org, 2003). The reservoirs of the pathogen for malaria are both malaria patients and their families (CDC, 2005). Malaria can be transmitted through many different modes. It can be passed congenitally (from a mother to her unborn child), through blood transfusions, from human to human contact, or by the anopheles mosquito (shands.org, 2003). The malaria pathogen can affect the liver, spleen, kidney, and the RBC's. Malaria can inflict damage on the liver and kidneys by causing them to fail. It can also cause an enlargement of the spleen, and destruction of the RBC's which causes anemia (shands.org, 2003). Most of this damage is inflicted by the massive release of merozoites into the blood stream. Remember, morozoites are one of the stages in the life cycle of the malarial plasmodium (they are formed during the asexual division of the schizont, a cell formed by the growth of a sporozoite or merozoite). Merozoites are released and invade other cells (biology-online.org, 2005). The anemia is caused by the destruction of RBC's, and the other problems in the body are caused by the large amounts of hemoglobin that are floating around in the system after the RBC's are destroyed (shands.org, 2003). People with malaria usually start to feel sick 10 days to 4 weeks after the initial infection of malaria, but people can start to feel sick as early as 8 days after the infection or even up to a year later (traveldoctor.org, 2005). There is some neurological sequaleae, in adults it is less than 5% of all the people infected, and in children it is more than 10% (Lokeshwar, 2000). The major signs and symptoms of malaria include: sequential chills, fever, sweating, headache, nausea, vomiting, muscle pain, anemia, bloody stools, jaundice, convulsion, and coma. At the doctor’s office health professionals may try to identify an enlarged liver or spleen, and will probably perform a malaria blood smear every 6 to 12 hours (shands.org, 2003). Malaria is a very resilient parasite that is constantly changing and adapting its life cycle. In each infection, the parasite changes its characteristics to avoid the victim’s immune system. Previous encounters which are beneficial for building antibodies are made less beneficial because of the changing disease. This makes it difficult for scientist, let alone the complexity of our immune system, to create a vaccine that is just as flexible and diverse as the parasite itself. For now, the only way to develop immunity is to be exposed to it for a long period of time. In areas where the risk of Malaria is high, children are in danger but if they survive through childhood, they develop a partial immunity. This immunity lasts if they are continually exposed. If they leave the geographical area for more than a couple of years, they will lose even partial immunity. Because mosquitoes are the carrier of this parasite, keeping it isolated long enough to destroy it is a major concern. There is good news though; there are cures for all four types, including the two fatal ones. Because Malaria has so many different faces, there are many levels of treatment and medicines. The two main types of treatment for malaria are suppressive and radical. In the suppressive stage, a drug is used to suppress the stage of the parasitic development. At the time, chloroquine or two new drugs, malarone or mefloquine (chloroquine is already becoming less and less effective) is being administered. P. falciparum malaria has strains that are already immune to this new drug. For the radical treatment, primaquine is administered to all cases. This drug prevents relapses and the spread of the infection by the mosquitoes by destroying the gametocytes. I have only mentioned 4 newer drugs. There are at least five others (and counting) because of the constantly evolving parasite. There is also a third course of action which is called a presumptive treatment. People exposed to areas where the spread of malaria is high, and who also come down with fever like symptoms, are to be treated as having malaria. This is a precautionary measure to prevent the spread of malaria and to catch the parasite in its early stage of reproduction. Once malaria has been diagnosed, doctors decide what type of drug to use and the length of time to use those drugs. Deciding factors in choosing drugs and length of time to use them include: which strain of malaria it is, where the patient was infected, how old the patient is, whether the patient is pregnant, how ill the patient is at the start of treatment, and if the patient has any allergies. The curing of malaria is a very tedious task. If done properly, the parasites will be eliminated and the patient will no longer be infected with malaria. If the parasite is immune to the drugs used, the wrong dose is used, or if the drug isn’t used for long enough, the parasite will remain (Dr. B.S. Kakkilaya, Center for Disease Control and Prevention). Although there is a cure, there are alternatives to medications. There are preventative measures to employ to keep from even being infected initially. Most precautions are ones we already take when camping or anytime when mosquitoes are present. Apply insect repellent which contains DEET as its active ingredient. Wear long pants and long-sleeve shirts and also spray insect repellent on your clothes because mosquitoes can pierce through thin layers. If indoors, sleep under a mosquito bed net. When possible use one that has been treated with insecticide. Also spray your room with insecticide before going to bed. Some insecticides dissipate throughout the night, so you may need to use slow burning mosquito coils to insure a constant facet of protection. Don’t walk through scrub or long grass after dark. Plan ahead before traveling to an area where malaria has been reported. See your doctor about 4-6 weeks before you leave to receive vaccinations and a prescription for an anti-malarial drug, if so desired. If you can survive the chemical bombardment of the repellants and sprays, you may be able to avoid getting malaria! (T.M.E. Davis B. Med Sc (hons), MB BS D Phil (Oxon), MRCP, FRACP and National Center for Infectious Diseases of Parasitic Diseases). Malaria not only causes chaos in an individual’s body, but causes one of the main obstructions for a whole countries economic growth. Countries that have a high infection rate of malaria are among the poorest in the world. It starts with individual families having over a quarter of their income going toward the cost of malaria treatment. Children have the most risk of dying; the parents respond by producing more kids which in turn make it impossible for the mother to work. Other cost include lost work time, cost of child births and deaths, costs of treatment and prevention, and finally an area that’s hard to put a price on, the pain and suffering of family deaths and sickness. To broaden the economic scope, malaria is a huge deterrent for businesses. Trade to countries with a high rate of malaria is drastically lower which also affects foreign investment, and commerce. Lastly, there is a decline in tourism in the afflicted nations. Each one of these factors may not be significant alone, put them together though and you’ll see the economic decline of a country. The economic decline can be traced to the parasitic carrying mosquito. Avoiding mosquito bites would significantly improve financial gains from each individual family, which would in turn cause improvements for the country. Bed nets are one of the most cost effective means of reducing deaths. Since mosquitoes bite at night, sleeping under a mosquito net filled with a natural biodegradable insecticide made from chrysanthemums is an important step for economic growth. Over 20 studies were done on nets which found that deaths were reduced by at least 20% and as much as 63%. Each bed net costs $5 to $10. A year’s natural insecticide costs less than a $1. Governments and large companies could emplace donation programs as a way of dispersing these nets. With a program like that in place, families and businesses would be on the rise, more drugs and money would be freed up for research. That could be a new beginning to the end of malaria.