Draft 1: Malaria: the Pestilence of Eden

This topic submitted by paul levy ( paulml52@hotmail.com) at 9:10 PM on 5/14/02.

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Malaria: The Pestilence of Eden

Paul Levy

Every year hundreds of millions of people suffer from a myriad of ailments that range from fatigue to severe delusions and in some cases death. Several common factors seem to tie many of these people together. Most of them live in or are traveling in tropical, humid areas with poor sanitation and high insect populations. Another trend is that many of the affected people are poor and live in third world countries. These millions of people are “united” together by Malaria, a blood parasite that is transmitted to humans by the Anopheles mosquito.
Malaria is common in most tropical countries with large non-urban populations, although infection is common in some urban settings. The highest incidence of malaria is in Africa, but cases are reported from Asia, Central and South America, the Indian subcontinent, the Middle East, Caribbean, and Oceania. The most common symptoms are similar to any flu like illness; fever, headache, joint stiffness and pain, fatigue, nausea, gastro-intestinal pain, and body aches. Malaria is caused by small blood parasites called Plasmodium. These small organisms have a well-defined life cycle and have many visible organelles similar to any eucharyotic cell that would be studied in a first year biology class (see pictures of Plasmodium Falciparum life cycle in the merozoite stage.) The parasite is only passed to humans by a specific genus of mosquito, the Anopheles.
There are currently drugs that treat malaria, but preventative drugs, known as chemoprophylactics, are the most common suggestion for travelers to endemic regions. In some human populations resistance to Malaria is not uncommon, especially in Africa, where there is actually a genetic cause for resistance in some native peoples. Before we discuss in any detail the actual physiology of Malaria, it is a good idea to examine the factors that lead to infection.
Since Malaria is only passed to humans through mosquito bites, it is possible to avoid the disease, even in areas of high incidence, by avoiding mosquito bites. The places most at risk are going to be places where mosquitoes are common and can reproduce well. Tropical, and often third world, environments are often the best suited to mosquito breeding, and thusly have the highest number of infected individuals. Removing pools of standing water, or use of insecticides can be affective means to control the mosquito populaton and consequently reduce malaria incidence. It is possible that Malaria could be passed to a human host by other means then mosquito bites such as blood transfusion or sharing needles with an infected individual. However, blood is tested for Plasmodium well before anybody receives the infusion, and sharing needles is uncommon in most third world countries where intravenous drug use is low or non-existent. Malaria often has magnified effects when contracted by pregnant women. The reasons for this are not entirely known, but complications are more common and it is known that immune system suppression is a probable cause for increased contraction (malaria) in pregnant women. It is likely that the immune system suppression that is responsible for increased malarial contraction rates in pregnant women is also responsible for the increased severity of the symptoms, but little research is available.
The most common symptoms of malaria are flu-like and can occur within a few days of infection or may take up to ten months (Bradley, 1996) and are cyclic in nature. This means that the original symptoms often subside within a few days or weeks, only to occur again in a few more weeks. Hemolysis is basis for the cyclic action of malaria in human hosts. Hemolysis is the rupturing of erythrocytes (Red Blood Cells) and occurs at the beginning of the life cycle for new malaria parasites. Plasmodium life cycle will be examined in more detail later, but the important concept here is that as the parasite reproduces, it kills erythrocytes and this is the predominant cause for malaria’s symptoms.
Some forms of malaria are more severe than others. For example, the Plasmodium Falciparum causes a much more severe malaria then the other common Plasmodia. Although it is more fatal to tourists, there is a 25% mortality rate for untreated tourists (GHS, 2002); it is still more severe than other strands in native populations as well. The symptoms of a P. falciparum infection may include dementia, hallucinations, internal bleeding, severely dehydrating diarrhea, loss of vision, and in some cases the surviving victim will experience permanent loss of liver and brain function (webMD.com). Death is much more common with infections of P. falciparum.
Many people that live in endemic regions have developed a resistance/tolerance to malaria infection. In some cases the infected person may not show any symptoms because his or her body is familiar with the parasite and has developed some defense mechanisms (webMD.com). This is not true in all cases and in many parts of the world there are still millions of dollars of losses in agriculture due to malaria infection. Malaria tends to be most common during the onset of the rainy season and the end of the rainy season, and in many cases these peaks tend to coincide with the spring planting and fall harvest of local farmers (Kricher, 1999). In some populations (mostly African, although world transportation and displacement of millions of Africans has altered the gene pool) there is a genetic basis for resistance to malaria. The Sickle-cell gene that is responsible for cycle cell anemia functions to protect African natives from malaria. The alteration of erythrocytes by a specific gene makes these people much less susceptible to malaria than people without the gene.
For all the non-immune people in the world, and that is most of the population, reoccurrences are common. The parasite can be left untreated and lie dormant for long periods of time in the liver. Re-occurrences have been reported up to 50 years after an initial exposure to malaria (webMD.com) and therefore prompt treatment is important. Many people fail to consider the repetitive cyclic action of malaria and are dumbfounded when the disease has a reoccurrence.
Many diseases other than malaria are caused by parasites and some parasites do not cause a specific disease, but rather feed on the host animal or plant tissues. Parasites such as a tapeworm are multicellular and consume food that would otherwise nourish the host animal. Fungal infections are also parasitic in nature because the fungus sustains itself by attaining nutrients from the host animal or plants body. Some parasites can survive without being dependent on a host, which is known as facultative parasitism. Others, malaria for instance, are obligate parasites and must live within a host to survive. There are several well-known malaria parasites. All are known collectively as Plasmodium (Blood parasites), and have similar life cycles. The four most widely recognized malaria parasites are: Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium falciparum. P. vivax, while not the most severe form of malaria, is known for having a long dormancy before initial symptoms appear in a human host. P. falciparum as discussed earlier can have many life threatening complications and is also very widely spread throughout Asia and Africa. There are several variations of P. falciparum according to the CDC and WHO that are beginning to develop tolerance to the second generation drugs for malaria (more on this later).
All of the malaria parasites have life cycles that are similar enough to be generalized to one systematic cycle; the only real difference is the duration the parasite lives in the liver before entering the blood. The parasites have a two-phase life cycle of which half is completed in the gut of a female Anopheles mosquito. This is known as the sexual stage and consists of micro and macro gametocytes maturing into macro and micro gametes (eggs and sperm respectively). Fertilization takes place (ahh, the miracle of life) in the mosquito’s digestive track to create a sporozoite. The sporozoite then travels to the mosquito’s salivary glands where it is now ready to be injected into a human, or in some rare instances a primate. The second half of the life cycle, known as the asexual phase, occurs in the blood and liver cells of the human host. The sporozoite penetrates liver cells and matures into a merozoite, which is released into the blood. In P. vivax and P. ovale a structure similar to a spore, known as a hypnozoite, remains in the liver and can cause reoccurrences years later if not properly treated (Bradley, 1996). The merozoites attach to erythrocytes (RBC’s) and invade them to live in the cell. The maturing merozoites pass through several phases; the ring phase and trophozoite stages. These stages are important only because the plasmodium is maturing, but have no specific relevance to the disease. Eventually, upon maturation and asexual reproduction, a schizont forms. This is the phase that coincides with symptoms because it is here that the host erythrocyte ruptures and releases new merozoites from the schizont. Some wonderful micrographs are available at www.wehi.edu.au/MalDB-www/encyc.html that display the size and internal organization or P. falciparum during each of the asexual stages. It is now easy to understand why the disease behaves in cyclic patters and why symptoms resemble anemia in many cases.
Diagnosis of malaria can be very complicated, so we will only examine the most common, and most effective methods. Two tests are usually administered to a patient; a thick and a thin blood smear. The thick blood smear is simply an undiluted sample of the patient’s blood. The physician examines the slide and looks for plasmodia in the erythrocytes or in the plasma. This test is usually administered several times if the initial test returns negative because the parasite may not have reproduced in large enough quantities for a single test to be conclusive. The thin blood smear test is a diluted sample of blood, which is examined only after the thick blood smear, has confirmed the presence of a malaria parasite in the patient. The physician must count all of the erythrocytes and determine approximately how many are infected out of the total. This ratio is used to determine the severity of the treatment that should be administered. The thin smear, while useful in determining the severity of the disease, is not always effective at predicting the severity of the symptoms experienced by the patient. The species of plasmodium is also of much more concern to many doctors that the percent of infected cells unless the number of infected cells is very high (25% infection rate would lead to extremely anemic symptoms and may require blood transfusions).
Treatment for diagnosed patients is simple, drugs. Malaria cannot be filtered out of the blood, and so it must be killed while in the blood. The drugs used to treat malaria are all poisons and often have side effects that are undesirable. The prophylactic drugs are similar in nature to the treatment drugs, but are usually weaker. Most effective drugs are dihydrochloride salts with an alkaloid base similar to quinine. There are several different versions, but all have similar action on the parasite although the exact mechanism is not fully understood. Research has shown that some drugs such as Pimaquine may work by interrupting electron transport chain in the parasite, but this is poorly understood and metabolites of the drug may be responsible (Bradley, 1996). Other drugs seem to have the ability to interrupt biosynthetic pathways in the parasites and protein synthesis in some cases. Many people experience mild nausea from the prophylactic drugs as well as visual problems and skin shedding in some. The drugs, since they are mildly toxic, can accumulate in the liver and in some people cause liver damage. This however is rare, and a far greater problem is resistance in some plasmodium species. Vaccines are currently being tested, but progress is slow because of the inability of the immune system to produce antibodies for a parasite of this size and because the parasite lives inside a human cell for so long.
Drug resistance is becoming more common in places where malaria is most common. P. falciparum resistance to Chloroquine is the rule in recent years, and many more drugs are loosing efficacy as the parasites have become more frequently exposed to them. Possible insect control mechanisms are being researched such as the use of Bacillus Thorengensis, a bacterium that kills insects, and use of strong insecticides such as DDT. However, these suggestions have huge ecological consequences because so far the insecticides (biological or chemical) are not species specific for Anopheles, and many insecticides are toxic to other animals as well.
It is likely that malaria will continue to be a problem in tropical climates for several reasons. Since the majority of human populations that live in malaria endemic regions are poor and uneducated it is likely that little will be done by locals to prevent infection. Many people are resistant to the point that they care little to pay for treatment. A greater problem may global warming. If the tropical climate were to expand, then so would the range of the Anopheles and malaria would no doubt follow. Rapid transportation is also a factor that may contribute to the spread of malaria to new and previously malaria free areas. About 50% of the world’s human population currently lives in areas where malaria is present, and the WHO suggests that these numbers are likely to increase in the 21st century. A good knowledge of malaria is important to the tropical traveler, now just as much as ever.


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