This is my first attempt to node my homework
. This paper was written in 2000. All facts contained herein, are current as of that date. The section "MECHANISMS OF MALARIA" was grafted in from a shorter paper of mine, and lacks citations. The facts in that section can be found in the same sources as the rest of the paper.
MALARIA: THE FOURTH HORSEMAN
THE SOCIO-ECONOMIC IMPACT OF MALARIA AND MALARIAL CONTROL ON SUB--SAHARAN WEST AFRICA
By Matthew Scouten
On the continent of Africa, there walks a murderer. For over 4,000 years, it has stalked humankind. It strikes at night, in your sleep. It lurks near water-- rivers, ponds, and swamps. Invisible to the human eye, it enters homes and leaves behind death. Its preferred victims: Children, pregnant women, refugees displaced by war and famine, the hungry and the poverty-stricken.
Who is this vile murderer? Is it a deranged military dictator, driven mad by power? Could it be some wild animal, driven from its habitat by human development? It is a disease. Its name is malaria, and its harbinger is the mosquito.
WHAT IS MALARIA?
Malaria is the second most deadly communicable disease in the world. Only tuberculosis kills more people per year than malaria17. This death toll, though, is only a small part of the cost that malaria exacts on society. The 3 to 5 hundred million victims who don’t die are very sick17, 5. They miss work, and someone must care for them. Symptoms include fever up to 106 degrees F, chills, sweating, headache, muscle pain and anemia. These symptoms are cyclic, recurring every 2 to 4 days. If not properly treated, victims often suffer from relapses months or even years later, throughout their life. Malaria is curable, but without treatment, it can cause death. In Africa, this treatment is too expensive for most victims.
CAUSES OF MALARIA
Malaria, like many tropical diseases, is caused by a parasite. Specifically, it is caused by the genus Plasmodium. Although there are many species of plasmodium, all spread by mosquitoes, only four of them can infect humans. These four are: P. Falciparum, P. Malariae, P. Vivax, and P. Ovale.
Malaria is spread by the female Anopheles mosquito. Anopheles mosquitoes are native to warmer climates with high humidity, such as those that can be found in non-Saharan Africa. It is not native to more temperate areas found in most of Europe and North America. The Anopheles mosquito prefers to feed at night.
The life cycle of malaria is complex. It involves multiple life stages in both the mosquito and human hosts. It also takes on many different forms and shapes. The life cycle includes many lesser cycles. First, there is the grand cycle of sexual reproduction in the mosquito, to asexual reproduction in the human hosts, and back again. Another is the blood cycle in which the plasmodium infects new red blood cells every 2 to 4 days. Externally, there is the short cycle of recurring symptoms (an effect of the blood cycle), and the long cycle of periodic relapse (an effect of the storage of disease organisms in the liver).
THE MECHANISMS OF MALARIA
When the female Anopheles mosquito bites a human, it injects a small amount of its own saliva to prevent blood clotting. Sometimes this saliva contains up to a thousand plasmodiums. When they first enter the blood, these plasmodiums are in a long thread-like form called sporozoites. These sporozoites travel through the blood to the liver. Those that survive the white blood cells that they encounter on the way, set up housekeeping in the liver and become schizonts.
These schizonts develop in the liver for 5 to 15 days (depending on their specific species). During this time, they can grow 50 times their original diameter. Their nuclei divide again and again until the cell contains as many as 40 thousand nuclei. Once it reaches maturity, the schizonts may do one or two things. Some of them will go dormant for years at a time only to infect a person at a later date. The rest of the schizonts shatter and become a new form, the tiny merozoits.
These merozoits enter the blood and scramble to infect red blood cells before the white blood cells can destroy them. Once it has successfully entered a red blood cell, the merozoit feeds on hemoglobin until it has eaten the red blood cells entire supply. Its nucleus then begins to divide at a rapid pace, and the Plasmodium once again takes the form of a schizont.
These second generation schizonts mature in 2 to 4 days, depending on species. Once they are fully mature, they break free of the now destroyed red blood cell and again shatter into merozoits. Because the red blood cells were all infected at about the same time, they also tend to rupture at about the same time. From the point of view of the immune system, a previously clean blood stream is suddenly infected with massive numbers of merozoits. The body responds to this sudden infection with a fever intended to kill off the invaders. The anemia is the result of the catastrophic loss of red blood cells.
The newborn merozoits must now scramble to invade new red blood cells before the immune system can eliminate them. If left untreated, this cycle can continue for up to 6-8 months before the body’s immune system can effectively clear the blood of malaria. However, a reserve of sporozoites remains resting in the liver, ready to break out and re-infect the blood even years after the original infection.
After 3-4 merozoit cycles in the blood, some of the infected red blood cells will not form schizonts. Instead, the Plasmodium will become a new form, the male and female gametocytes. These gametocytes will go dormant inside a red blood cell and wait for a new mosquito to bite. If a new mosquito bites the infected human, there is a chance that some of the blood that it takes in will contain these gametocytes. If the mosquito is an Anopheles mosquito, then chemical signatures in its digestive tract will signal the gametocytes to break out of their red blood cell. The male gametocytes will then attempt to locate and fertilize a female. The fertilized females immediately become oöcysts.
These oöcysts immediately make their way to the mosquito’s saliva glands. Once they reach the saliva glands, the oöcysts develop into sporozoites. If the mosquito bites again, then the sporozoites stand a chance of being transmitted back into a blood stream. If this blood stream is human, then they stand a chance of making it back to the liver to begin the cycle again.
The four different species of Plasmodium that infect humans all have different characteristics. One of these is the length of time between merozoit outbreaks. For P. Falciparum and P. Malariae, the cycle is 3 days long. P. Vivax and P. Ovale have 2 day cycles.
The different types also vary in deadliness. P. Falciparum is the most recently adapted to infecting humans, and, as such, is also the deadliest. One reason is that P. Falciparum merozoits infect all types of red blood cells, whereas P.Vivax, the least deadly, infects only the young cells, and P.Ovale and P. Malariae infect only the older cells.
Another reason for Falciparum’s unique deadliness is that it tends to make the red blood cells slightly “sticky”. This can cause the cells to form clumps. If such a clump gets lodged in the capillaries serving a vital organ, it can block blood flow to a small region. If many such clumps become lodged in the brain, they can cause mental disturbance, seizures, and eventually unconsciousness and usually death. Fortunately, unlike the other species, P. Falciparum does not leave reserve forces behind in the liver. Once the malaria has been cleared out of the blood, it will stay gone rather than recurring years later.
WHO DOES IT EFFECT?
Malaria is a major public health issue in more than 90 countries17, 5. This includes some 2.4 billion people or 40% of the world’s population. Worldwide an estimated 300-500 million cases of malaria occur each year5, 16. Malaria kills 1.5-2.7 million people per year17, 8. Malaria accounts for 2.3% of all global disease8. This even includes all the millions of Americans who had the common cold or a simple flu. In Africa, this figure rises to 9%. Ninety percent of all Malaria deaths occur in Sub-Saharan Africa17. In affected areas, 3 out of 10 hospital beds are occupied by malaria patients 17.
Malaria used to be a problem practically all over the world. In Europe, most parts of Asia, and the United States, vector control programs (aimed at reducing the number of anopheles mosquitoes) have been very effective. In fact, since the first quarter of this century, malaria has been considered virtually eradicated on all continents except Africa and small parts of South America and Southern Europe.
Malaria has a special affinity for pregnant women and children. In Africa, 90% of all deaths due to malaria are children under five years of age8. That is over 3,000 children per day or one child every 30 seconds14. Babies are born with little or no immunity to malaria. Immunity to malaria is acquired later in life, after one or two attacks. In malaria-affected areas, children are often not named until their first birthday. It is common for children to die before then. Even if a child survives malaria, their development will often be stunted by the loss of energy and nutrients due to severe anemia17.
Pregnant women are also especially susceptible to malaria. Among non-immune pregnant women, the chance of miscarriage due to malaria is 60%10. Death is also more likely when mixing malaria with pregnancy. Ten percent of all non-immune pregnant women who contract malaria die10. For unknown reasons, even immune women tend to lose much of their immunity during pregnancy. Women who are pregnant are 4 times more likely to be infected by malaria than non-pregnant women. They are also half as likely to survive malaria5. A baby whose mother had malaria during pregnancy can be born with malaria. It is also more likely that such a baby will have severe physical and mental impairment later in life10.
The effects of malaria are particularly brutal on those in impoverished areas. In the rainy season, the anopheles mosquito multiplies and spreads the disease. In Africa, the rainy season also happens to be just before the harvest season, when people have the least money and are the most hungry3. A bout of malaria during this time destroys about 10 working days during harvest season (not counting the efforts of those who treat the affected person)17, 5. Families affected by malaria will only clear 40% of the cropland that a healthy family would clear17. During the rainy season, treatment may not be available due to the fact that the heavy rains often result in the roads being blocked. Also, proper treatment, when available, can cost up to a fourth of a poor family's income5.
This devastating cost on the individual level places a heavy burden on the economies of nations that already owe huge debts to wealthier countries. If malaria had been eliminated 45 years ago, then sub-Saharan Africa’s gross domestic product would be 32% greater today9. This equates to about 100 billion dollars per year9.
Malaria exacts its economic costs through many channels. Every workday missed due to malaria reduces national productivity. Also, the cost of drugs and hospitalization is enormous. In affected areas, malaria accounts for 10 percent of all hospital admissions and 30 percent of all doctors visits5. In 1997, malaria cost sub-Saharan Africa 2 billion dollars in direct and indirect costs17, 14.
The poorest African countries can only afford to spend about 2 dollars per person on public health10. This is not enough. The cost of treatment is far greater than 2 dollars per person. Even the cost of prevention, although cheaper than treatment, is greater than the money available.
METHODS OF TREATMENT AND PREVENTION
Both the treatment and prevention of malaria may be accomplished with drugs. Quinine, the first anti-malarial drug is derived from a tree native to South America. Although it was effective against malaria, quinine had several drawbacks. One was that its extremely bitter taste made some reluctant to take it regularly as a prophylactic. Also continued use of quinine for long periods of time can result in hearing loss. Although it reduces the chance of catching malaria, quinine increases the chance of contracting Black Water Fever, which is almost as deadly as malaria. The final blow came with the discovery of quinine resistant strains of malaria.
The drug chloroquine (also chlorofluroquine) was effective against malaria stored in the liver. It was also effective against malaria in the blood, and as a prophylactic. Most strains of Malaria, however, have now become resistant to it. The current drug of choice is Mefloquine, although doctors and scientists have noticed a rising resistance to this drug as well. Scientists are working hard to find a replacement for Mefloquine in the event that it someday becomes completely ineffective. Fortunately, it is rare for the malaria in any one area to be resistant to more than one or two drugs.
The biggest problem with drugs, however, is that they are expensive. The cost of treating all of Africa with prophylactic drugs would be enormous. Also, if malaria were not completely eliminated, then anyone who quit the drugs would have weakened immunity to the disease.
One of the most effective ways to prevent malaria is also one of the simplest and cheapest. Sleeping under mosquito nets treated with a natural insecticide drastically reduces the number of mosquito bites. Because malaria is spread exclusively by the Anopheles mosquito, fewer bites mean less chance of catching malaria. Numerous studies have established that sleeping under mosquito nets reduces child death due to malaria 20 to 63 percent5, 17
Why then, if bed nets are so effective, isn’t every African child sleeping under one? One reason is that people don’t know. In one study in Ghana, one half of all those surveyed did not know that mosquito bites caused malaria17! If someone does not understand the link between mosquitoes and malaria, it is difficult to convince them to sleep under mosquito nets. If someone came to you and told you that wearing a pointy hat would prevent cancer, would you wear it? Probably not.
The other reason is cost. Although a bed net cost only $4-$61, many African nations have heavy taxes on bed nets and insecticides15. With taxes, a bed net price may be as high as 20 dollars3. This price is far too expensive for most African families. The reason that the taxes on bed nets are so high is that they are used mainly by Westerners who travel in Africa. One reason that only westerners use them, is that the tax is so high that no one else can afford them. The African nations prefer to tax westerners because their own people cannot afford much taxation at all. They cannot afford taxation because they are poor. They are poor in part because they have malaria. And, perversely, they have malaria because they cannot afford bed nets!
THE WAR ON MALARIA
In 1997, fifty-three African heads of state passed a resolution in the Organization for African Unity asking the wealthier nations of the world for help in dealing with malaria5. On Oct. 30th, 1998, “Roll Back Malaria” was founded as a joint program of the World Health Organization (WHO), the United Nations Development Program (UNDP), United Nations Children’s Fund (UNICEF), and the World Bank17. The goal of the Roll Back Malaria (RBM) program is to halve all malaria deaths by 2010, and halve them again by 2015. The main efforts will be concentrated on education, special loans for the purchase of mosquito nets, and the development of new drugs.
In order to combat malaria, it is important that its victims understand the disease. In Africa, 80% of all malaria cases are treated in the home5. One of the primary goals of the Roll Back Malaria program is training mothers to recognize the symptoms of malaria and seek appropriate treatment. About 86% of African mothers, when confronted with malaria, take only anti fever measures13. Although fever control is an important part of treating malaria, much more can be done by Western medicine. Even if the family can afford appropriate drugs, however, they may be reluctant to seek the aide of western medicine. As many as 75 percent of mothers surveyed believed that if a child with a fever received an injection, it would cause convulsions or death13. This belief may be due in part to the fact that many mothers would not seek help from western medicine until convulsions and death were inevitable anyway! Finally, it is important that people understand why they are being asked to sleep under bed nets.
Education is only the beginning of prevention. Bed nets must be made affordable to the average African family. One way of doing this is to eliminate the taxes and tariffs on importing bed nets into Africa. Two African nations, Tanzania and Uganda, have recently done just that. As a result, the price of bed nets in these countries has dropped to $3.5015. Also, the World Bank has instituted a program of special loans for the purchase of bed nets. These loans to Malaria affected nations would allow the distribution of bed nets to families living in impoverished areas. According to Nils Daulaire, president of the Global Health Council, “Nobody leaves from the hospital any more without a child car seat in the U.S., but that doesn’t make more than a 5% difference in our child death rate. With malaria, no mother in Africa should leave the hospital without a bed net”3. In Africa, bed nets make a 20 to 63% difference in child mortality5, 17.
In order to combat malaria on a more effective scale, new drugs are needed. Although the malaria Plasmodium slowly grows in resistance to our existing pharmacopoeia of anti-malarial drugs, there has been very little effort to discover new ones. In 1997, not a single major western pharmaceutical company was engaged in malaria research. The reason for this is simple. The cost of developing a new drug from first concept to market is about $500 million dollars5. Pharmaceutical companies quite reasonably expect to make a profit off the sale of the drugs that they develop. The victims of malaria, however, have very little money (primarily because of malaria). Worldwide, a total of $84 million is spent on malarial research5. This is 1/50th the amount that the U.S. spends each year on car research, and certainly less than the $500 million necessary to develop new drugs5. For every death due to malaria, $42 is spent on research. For HIV, $3,270 is spent for every death, and for asthma, $789.
More recently, the Medicines for Malaria Venture (MMV) incorporated as a non-profit research organization under Swiss law. The MMV operates like a small research and development company. The primary purpose of the MMV is to develop affordable new drugs for malaria every one to five years, with the first becoming available by 2010. Although the MMV is currently funded by private and governmental donations, it is planned that it will use money from the licensing of newly developed drugs to fund further research.
Fortunately, money available for malaria research has been increasing. Next year(2001), the World Bank will be pledging $300-$500 million in interest-free loans to fight malaria7. This would be enough to fund meaningful drug research. Also, the Bill and Melinda Gates Foundation is donating $115 million directly to education and drug research for malaria. Finally, the National Institute of Allergy and Infectious Diseases is expected to raise their malarial research budget above $52 million in 20017.
On the scientific front, preliminary research is being done on a handful of promising anti-malarial candidates7. Although results are still several years away, the mere fact that research into malarial drugs is occurring is a marked improvement from the situation as of 1997. Also, the genome of Plasmodium Falciparum has recently been completely sequenced11. Although it has not yet been fully released (due to squabbling over intellectual property rights), every bit of knowledge aids in the fight against this deadly foe.
The knights in shining white lab coats ride from the west. They wield scalpels and test tubes. They carry shields of mosquito netting and a quiver full of drugs. Some fight the Killer’s mighty allies - War, Poverty, Ignorance and Apathy. Others search - perhaps in vain -- for the Holy Grail of Vaccine. Will they arrive in time? Will they smote the Dark Plague? Only the spirits know.
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- Harrison, Gordon. Mosquitoes, Malaria & Man: A History of Hostilities Since 1880. New York: E.P. Dutton, 1978.
- Hsu, Karen. “Bed Nets Promoted to Reduce Malaria.” Boston Globe. 10/13/99. Accessed: 10/28/00: A7. < http://www.malaria.org/news116.html >
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- Nchinda, Thomas C. United States. Center for Disease Control and Prevention. “Malaria: A Reemerging Disease in Africa.” Emerging Infectious Diseases Vol 4 No 3. Atlanta: 11/16/2000. Accessed: 10/28/00 <http://www.cdc.gov/ncidod/EID/vol3no4/nchinda.htm>
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- Ransford, Oliver. ‘Bid the Sickness Cease’: Disease in the History of Black Africa. London: John Murray, Ltd., 1983.
- Tarimo, D. S., et al. “Mothers’ perceptions and knowledge on childhood malaria in the holendemic Kibaha district, Tanzania: implications for malaria control and the IMCI strategy.” Tropical Medicine & International Health. 5(3): 179-184, March 2000. Abstract. Ovid. Ibis. Accessed: 10/28/00.
- United Nations. United Nations Children’s Fund. “Controlling Malaria.” Geneva. Accessed: 10/29/00 <http://www.unicef.org/programme/health/malaria/malaria.htm>
- United Nations. World Health Organization. “African Nations Urged To End ‘Malaria Taxes’: Uganda sets life-saving example.” Geneva: 07/05/00. Accessed: 10/28/00 <http://www.who.int/inf-pr-2000/en/pr2000-48.html>
- United Nations. World Health Organization. Background Document: Introducing MMV. Geneva: 1999. Accessed: 10/29/00 <http://www.who.int/inf-fs/en/factXXX.html>
- United Nations. World Health Organization. “Fact Sheet No 94: Malaria.” Geneva: 1998. Accessed: 10/28/00 <http://www.who.int/inf-fs/en/fact094.html>