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Malaria

Malaria

Definition

Malaria is a serious infectious disease spread by certain mosquitoes. It is most common in tropical climates. It is characterized by recurrent symptoms of chills, fever, and an enlarged spleen. The disease can be treated with medication, but it often recurs. Malaria is endemic (occurs frequently in a particular locality) in many third world countries. Isolated, small outbreaks sometimes occur within the boundaries of the United States.

Description

Malaria is a growing problem in the United States. Although only about 1400 new cases were reported in the United States and its territories in 2000, many involved returning travelers. In addition, locally transmitted malaria has occurred in California, Florida, Texas, Michigan, New Jersey, and New York City. While malaria can be transmitted in blood, the American blood supply is not screened for malaria. Widespread malarial epidemics are far less likely to occur in the United States, but small localized epidemics could return to the Western world. As of late 2002, primary care physicians are being advised to screen returning travelers with fever for malaria, and a team of public health doctors in Minnesota is recommending screening immigrants, refugees, and international adoptees for the diseaseparticularly those from high-risk areas.

The picture is far more bleak, however, outside the territorial boundaries of the United States. A recent government panel warned that disaster looms over Africa from the disease. Malaria infects between 300 and 500 million people every year in Africa, India, southeast Asia, the Middle East, Oceania, and Central and South America. A 2002 report stated that malaria kills 2.7 million people each year, more than 75 percent of them African children under the age of five. It is predicted that within five years, malaria will kill about as many people as does AIDS. As many as half a billion people worldwide are left with chronic anemia due to malaria infection. In some parts of Africa, people battle up to 40 or more separate episodes of malaria in their lifetimes. The spread of malaria is becoming even more serious as the parasites that cause malaria develop resistance to the drugs used to treat the condition. In late 2002, a group of public health researchers in Thailand reported that a combination treatment regimen involving two drugs known as dihydroartemisinin and azithromycin shows promise in treating multidrug-resistant malaria in southeast Asia.

Causes and symptoms

Human malaria is caused by four different species of a parasite belonging to genus Plasmodium: Plasmodium falciparum (the most deadly), Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale. The last two are fairly uncommon. Many animals can get malaria, but human malaria does not spread to animals. In turn, animal malaria does not spread to humans.

A person gets malaria when bitten by a female mosquito who is looking for a blood meal and is infected with the malaria parasite. The parasites enter the blood stream and travel to the liver, where they multiply. When they re-emerge into the blood, symptoms appear. By the time a patient shows symptoms, the parasites have reproduced very rapidly, clogging blood vessels and rupturing blood cells.

Malaria cannot be casually transmitted directly from one person to another. Instead, a mosquito bites an infected person and then passes the infection on to the next human it bites. It is also possible to spread malaria via contaminated needles or in blood transfusions. This is why all blood donors are carefully screened with questionnaires for possible exposure to malaria.

It is possible to contract malaria in non-endemic areas, although such cases are rare. Nevertheless, at least 89 cases of so-called airport malaria, in which travelers contract malaria while passing through crowded airport terminals, have been identified since 1969.

The amount of time between the mosquito bite and the appearance of symptoms varies, depending on the strain of parasite involved. The incubation period is usually between 8 and 12 days for falciparum malaria, but it can be as long as a month for the other types. Symptoms from some strains of P. vivax may not appear until 8-10 months after the mosquito bite occurred.

The primary symptom of all types of malaria is the "malaria ague" (chills and fever). In most cases, the fever has three stages, beginning with uncontrollable shivering for an hour or two, followed by a rapid spike in temperature (as high as 106°F), which lasts three to six hours. Then, just as suddenly, the patient begins to sweat profusely, which will quickly bring down the fever. Other symptoms may include fatigue, severe headache, or nausea and vomiting. As the sweating subsides, the patient typically feels exhausted and falls asleep. In many cases, this cycle of chills, fever, and sweating occurs every other day, or every third day, and may last for between a week and a month. Those with the chronic form of malaria may have a relapse as long as 50 years after the initial infection.

Falciparum malaria is far more severe than other types of malaria because the parasite attacks all red blood cells, not just the young or old cells, as do other types. It causes the red blood cells to become very "sticky." A patient with this type of malaria can die within hours of the first symptoms. The fever is prolonged. So many red blood cells are destroyed that they block the blood vessels in vital organs (especially the kidneys), and the spleen becomes enlarged. There may be brain damage, leading to coma and convulsions. The kidneys and liver may fail.

Malaria in pregnancy can lead to premature delivery, miscarriage, or stillbirth.

Certain kinds of mosquitoes (called anopheles) can pick up the parasite by biting an infected human. (The more common kinds of mosquitoes in the United States do not transmit the infection.) This is true for as long as that human has parasites in his/her blood. Since strains of malaria do not protect against each other, it is possible to be reinfected with the parasites again and again. It is also possible to develop a chronic infection without developing an effective immune response.

Diagnosis

Malaria is diagnosed by examining blood under a microscope. The parasite can be seen in the blood smears on a slide. These blood smears may need to be repeated over a 72-hour period in order to make a diagnosis. Antibody tests are not usually helpful because many people developed antibodies from past infections, and the tests may not be readily available. A new laser test to detect the presence of malaria parasites in the blood was developed in 2002, but is still under clinical study.

Two new techniques to speed the laboratory diagnosis of malaria show promise as of late 2002. The first is acridine orange (AO), a staining agent that works much faster (3-10 min) than the traditional Giemsa stain (45-60 min) in making the malaria parasites visible under a microscope. The second is a bioassay technique that measures the amount of a substance called histadine-rich protein II (HRP2) in the patient's blood. It allows for a very accurate estimation of parasite development. A dip strip that tests for the presence of HRP2 in blood samples appears to be more accurate in diagnosing malaria than standard microscopic analysis.

Anyone who becomes ill with chills and fever after being in an area where malaria exists must see a doctor and mention their recent travel to endemic areas. A person with the above symptoms who has been in a high-risk area should insist on a blood test for malaria. The doctor may believe the symptoms are just the common flu virus. Malaria is often misdiagnosed by North American doctors who are not used to seeing the disease. Delaying treatment of falciparum malaria can be fatal.

Treatment

Falciparum malaria is a medical emergency that must be treated in the hospital. The type of drugs, the method of giving them, and the length of the treatment depend on where the malaria was contracted and how sick the patient is.

For all strains except falciparum, the treatment for malaria is usually chloroquine (Aralen) by mouth for three days. Those falciparum strains suspected to be resistant to chloroquine are usually treated with a combination of quinine and tetracycline. In countries where quinine resistance is developing, other treatments may include clindamycin (Cleocin), mefloquin (Lariam), or sulfadoxone/pyrimethamine (Fansidar). Most patients receive an antibiotic for seven days. Those who are very ill may need intensive care and intravenous (IV) malaria treatment for the first three days.

Anyone who acquired falciparum malaria in the Dominican Republic, Haiti, Central America west of the Panama Canal, the Middle East, or Egypt can still be cured with chloroquine. Almost all strains of falciparum malaria in Africa, South Africa, India, and southeast Asia are now resistant to chloroquine. In Thailand and Cambodia, there are strains of falciparum malaria that have some resistance to almost all known drugs.

A patient with falciparum malaria needs to be hospitalized and given antimalarial drugs in different combinations and doses depending on the resistance of the strain. The patient may need IV fluids, red blood cell transfusions, kidney dialysis, and assistance breathing.

A drug called primaquine may prevent relapses after recovery from P. vivax or P. ovale. These relapses are caused by a form of the parasite that remains in the liver and can reactivate months or years later.

Another new drug, halofantrine, is available abroad. While it is licensed in the United States, it is not marketed in this country and it is not recommended by the Centers for Disease Control and Prevention in Atlanta.

Alternative treatments

The Chinese herb qiinghaosu (the Western name is artemisinin) has been used in China and southeast Asia to fight severe malaria, and became available in Europe in 1994. Because this treatment often fails, it is usually combined with another antimalarial drug (mefloquine) to boost its effectiveness. It is not available in the United States and other parts of the developed world due to fears of its toxicity, in addition to licensing and other issues.

A Western herb called wormwood (Artemesia annua ) that is taken as a daily dose can be effective against malaria. Protecting the liver with herbs like goldenseal (Hydrastis canadensis ), Chinese goldenthread (Coptis chinensis ), and milk thistle (Silybum marianum ) can be used as preventive treatment. Preventing mosquitoes from biting you while in the tropics is another possible way to avoid malaria.

As of late 2002, researchers are studying a traditional African herbal remedy against malaria. Extracts from Microglossa pyrifolia, a trailing shrub belonging to the daisy family (Asteraceae), show promise in treating drug-resistent strains of P. falciparum.

Prognosis

If treated in the early stages, malaria can be cured. Those who live in areas where malaria is epidemic, however, can contract the disease repeatedly, never fully recovering between bouts of acute infection.

Prevention

Several researchers are currently working on a malarial vaccine, but the complex life cycle of the malaria parasite makes it difficult. A parasite has much more genetic material than a virus or bacterium. For this reason, a successful vaccine has not yet been developed.

Malaria is an especially difficult disease to prevent by vaccination because the parasite goes through several separate stages. One recent promising vaccine appears to have protected up to 60% of people exposed to malaria. This was evident during field trials for the drug that were conducted in South America and Africa. It is not yet commercially available.

The World Health Association (WHO) has been trying to eliminate malaria for the past 30 years by controlling mosquitoes. Their efforts were successful as long as the pesticide DDT killed mosquitoes and antimalarial drugs cured those who were infected. Today, however, the problem has returned a hundred-fold, especially in Africa. Because both the mosquito and parasite are now extremely resistant to the insecticides designed to kill them, governments are now trying to teach people to take antimalarial drugs as a preventive medicine and avoid getting bitten by mosquitoes.

A newer strategy as of late 2002 involves the development of genetically modified non-biting mosquitoes. A research team in Italy is studying the feasibility of this means of controlling malaria.

Travelers to high-risk areas should use insect repellant containing DEET for exposed skin. Because DEET is toxic in large amounts, children should not use a concentration higher than 35%. DEET should not be inhaled. It should not be rubbed onto the eye area, on any broken or irritated skin, or on children's hands. It should be thoroughly washed off after coming indoors.

Those who use the following preventive measures get fewer infections than those who do not:

  • Between dusk and dawn, remain indoors in well-screened areas.
  • Sleep inside pyrethrin or permethrin repellent-soaked mosquito nets.
  • Wear clothes over the entire body.

Anyone visiting endemic areas should take antimalarial drugs starting a day or two before they leave the United States. The drugs used are usually chloroquine or mefloquine. This treatment is continued through at least four weeks after leaving the endemic area. However, even those who take antimalarial drugs and are careful to avoid mosquito bites can still contract malaria.

International travelers are at risk for becoming infected. Most Americans who have acquired falciparum malaria were visiting sub-Saharan Africa; travelers in Asia and South America are less at risk. Travelers who stay in air conditioned hotels on tourist itineraries in urban or resort areas are at lower risk than backpackers, missionaries, and Peace Corps volunteers. Some people in western cities where malaria does not usually exist may acquire the infection from a mosquito carried onto a jet. This is called airport or runway malaria.

KEY TERMS

Arteminisinins A family of antimalarial products derived from an ancient Chinese herbal remedy. Two of the most popular varieties are artemether and artesunate, used mainly in southeast Asia in combination with mefloquine.

Chloroquine An antimalarial drug that was first used in the 1940s, until the first evidence of quinine resistance appeared in the 1960s. It is now ineffective against falciparum malaria almost everywhere. However, because it is inexpensive, it is still the antimalarial drug most widely used in Africa. Native individuals with partial immunity may have better results with chloroquine than a traveler with no previous exposure.

Mefloquine An antimalarial drug that was developed by the United States Army in the early 1980s. Today, malaria resistance to this drug has become a problem in some parts of Asia (especially Thailand and Cambodia).

Mefloquine An antimalarial drug that was developed by the United States Army in the early 1980s. Today, malaria resistance to this drug has become a problem in some parts of Asia (especially Thailand and Cambodia).

Quinine One of the first treatments for malaria, quinine is a natural product made from the bark of the Cinchona tree. It was popular until being superseded by the development of chloroquine in the 1940s. In the wake of widespread chloroquine resistance, however, it has become popular again. Quinine, or its close relative quinidine, can be given intravenously to treat severe Falciparum malaria.

Sulfadoxone/pyrimethamine (Fansidar) An antimalarial drug developed in the 1960s. It is the first drug tried in some parts of the world where chloroquine resistance is widespread. It has been associated with severe allergic reactions due to its sulfa component.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Extraintestinal Protozoa: Malaria." Section 13, Chapter 161. In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

PERIODICALS

Causer, Louise M, et al. "Malaria SurveillanceUnited States, 2000." Morbidity and Mortality Weekly Report July 12, 2002: 9-15. Abstract.

Coluzzi, M., and C. Costantini. "An Alternative Focus in Strategic Research on Disease Vectors: The Potential of Genetically Modified Non-Biting Mosquitoes." Parassitologia 44 (December 2002): 131-135.

"Combination Approach Results in Significant Drop in Malaria Rates in Viet Nam." TB & Outbreaks Week Abstract (September 24, 2002): 17.

Devi, G., V. A. Indumathi, D. Sridharan, et al. "Evaluation of ParaHITf Strip Test for Diagnosis of Malarial Infection." Indian Journal of Medical Science 56 (October 2002): 489-494.

Keiser, J., J. Utzinger, Z. Premji, et al. "Acridine Orange for Malaria Diagnosis: Its Diagnostic Performance, Its Promotion and Implementation in Tanzania, and the Implications for Malaria Control." Annals of Tropical Medicine and Parasitology 96 (October 2002): 643-654.

Kohler, I., K. Jenett-Siems, C. Kraft, et al. "Herbal Remedies Traditionally Used Against Malaria in Ghana: Bioassay-Guided Fractionation of Microglossa pyrifolia (Asteraceae)." Zur Naturforschung 57 (November-December 2002): 1022-1027.

Krudsood, S., K. Buchachart, K. Chalermrut, et al. "A Comparative Clinical Trial of Combinations of Dihydroartemisinin Plus Azithromycin and Dihydroartemisinin Plus Mefloquine for Treatment of Multidrug-Resistant Falciparum Malaria." Southeast Asian Journal of Tropical Medicine and Public Health 33 (September 2002): 525-531.

"Laser-based Malaria Test could be Valuable." Medical Devices & Surgical Technology Week September 22, 2002: 4.

McClellan, S. L. "Evaluation of Fever in the Returned Traveler." Primary Care 29 (December 2002): 947-969.

"Multilateral Initiative on Malaria to Move to Sweden." TB & Outbreaks Week September 24, 2002: 17.

Noedl, H., C. Wongsrichanalai, R. S. Miller, et al. "Plasmodium falciparum: Effect of Anti-Malarial Drugs on the Production and Secretion Characteristics of Histidine-Rich Protein II." Experimental Parasitology 102 (November-December 2002): 157-163.

"Promising Vaccine May Provide Long-Lasting Protection." Medical Letter on the CDC & FDA September 15, 2002: 14.

Stauffer, W. M., D. Kamat, and P. F. Walker. "Screening of International Immigrants, Refugees, and Adoptees." Primary Care 29 (December 2002): 879-905.

Thang, H. D., R. M. Elsas, and J. Veenstra. "Airport Malaria: Report of a Case and a Brief Review of the Literature." Netherlands Journal of Medicine 60 (December 2002): 441-443.

ORGANIZATIONS

Centers for Disease Control Malaria Hotline. (770) 332-4555.

Centers for Disease Control Travelers Hotline. (770) 332-4559.

OTHER

Malaria Foundation Page. http://www.malaria.org.

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Malaria

Malaria

Definition

Malaria is a serious infectious disease spread by certain mosquitoes. It is most common in tropical climates. It is characterized by recurrent symptoms of chills, fever , and an enlarged spleen. The disease can be treated with medication, but it often recurs. Malaria is endemic (occurs frequently in a particular locality) in many third world countries. Isolated, small outbreaks sometimes occur within the boundaries of the United States, with most of the cases reported as having been imported from other locations.

Description

Malaria is a growing problem in the United States. Although only about 1400 new cases were reported in the United States and its territories in 2000, many involved returning travelers. In addition, locally transmitted malaria has occurred in California, Florida, Texas, Michigan, New Jersey, and New York City. While malaria can be transmitted in blood, the American blood supply is not screened for malaria. Widespread malarial epidemics are far less likely to occur in the United States, but small localized epidemics could return to the Western world. As of late 2002, primary care physicians are being advised to screen returning travelers with fever for malaria, and a team of public health doctors in Minnesota is recommending screening immigrants, refugees, and international adoptees for the diseaseparticularly those from high-risk areas.

The picture is far more bleak, however, outside the territorial boundaries of the United States. A recent government panel warned that disaster looms over Africa from the disease. Malaria infects between 300 and 500 million people every year in Africa, India, southeast Asia, the Middle East, Oceania, and Central and South America. A 2002 report stated that malaria kills 2.7 million people each year, more than 75 percent of them African children under the age of five. It is predicted that within five years, malaria will kill about as many people as does AIDS . As many as half a billion people worldwide are left with chronic anemia due to malaria infection. In some parts of Africa, people battle up to 40 or more separate episodes of malaria in their lifetimes. The spread of malaria is becoming even more serious as the parasites that cause malaria develop resistance to the drugs used to treat the condition. In late 2002, a group of public health researchers in Thailand reported that a combination treatment regimen involving two drugs known as dihydroartemisinin and azithromycin shows promises in treating multidrug-resistant malaria in southeast Asia.

Causes & symptoms

Human malaria is caused by four different species of a parasite belonging to genus Plasmodium : Plasmodium falciparum (the most deadly), Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale. The last two are fairly uncommon. Many animals can get malaria, but human malaria does not spread to animals. In turn, animal malaria does not spread to humans.

A person gets malaria when bitten by a female mosquito seeking a blood meal that is infected with the malaria parasite. The parasites enter the blood stream and travel to the liver, where they multiply. When they reemerge into the blood, symptoms appear. By the time a patient shows symptoms, the parasites have reproduced very rapidly, clogging blood vessels and rupturing blood cells.

Malaria cannot be casually transmitted directly from one person to another. Instead, a mosquito bites an infected person and then passes the infection on to the next human it bites. It is also possible to spread malaria via contaminated needles or in blood transfusions. This is why all blood donors are carefully screened with questionnaires for possible exposure to malaria.

It is possible to contract malaria in non-endemic areas, although such cases are rare. Nevertheless, at least 89 cases of so-called airport malaria, in which travelers contract malaria while passing through crowded airport terminals, have been identified since 1969.

The amount of time between the mosquito bite and the appearance of symptoms varies, depending on the strain of parasite involved. The incubation period is usually between eight and 12 days for falciparum malaria, but it can be as long as a month for the other types. Symptoms from some strains of P. vivax may not appear until eight to 10 months after the mosquito bite occurred.

The primary symptom of all types of malaria is the "malaria ague" (chills and fever), which corresponds to the "birth" of the new generation of the parasite. In most cases, the fever has three stages, beginning with uncontrollable shivering for an hour or two, followed by a rapid spike in temperature (as high as 106°F [41.4°C]), which lasts three to six hours. Then, just as suddenly, the patient begins to sweat profusely, which will quickly bring down the fever. Other symptoms may include fatigue , severe headache , or nausea and vomiting . As the sweating subsides, the patient typically feels exhausted and falls asleep. In many cases, this cycle of chills, fever, and sweating occurs every other day, or every third day, and may last for between a week and a month. Those with the chronic form of malaria may have a relapse as long as 50 years after the initial infection.

Falciparum malaria is far more severe than other types of malaria because the parasite attacks all red blood cells, not just the young or old cells, as do other types. It causes the red blood cells to become very "sticky." A patient with this type of malaria can die within hours of the first symptoms. The fever is prolonged. So many red blood cells are destroyed that they block the blood vessels in vital organs (especially the brain and kidneys), and the spleen becomes enlarged. There may be brain damage, leading to coma and convulsions. The kidneys and liver may fail.

Malaria in pregnancy can lead to premature delivery, miscarriage, or stillbirth.

Certain kinds of mosquitoes belonging to the genus Anopheles can pick up the parasite by biting an infected human. (The more common kinds of mosquitoes in the United States do not transmit the infection.) This is true for as long as that human has parasites in his/her blood. Since strains of malaria do not protect against each other, it is possible to be reinfected with the parasites again and again. It is also possible to develop a chronic infection without developing an effective immune response.

Diagnosis

Malaria is diagnosed by examining blood under a microscope. The parasite can be seen in the blood smears on a slide. These blood smears may need to be repeated over a 72-hour period in order to make a diagnosis. Antibody tests are not usually helpful because many people developed antibodies from past infections , and the tests may not be readily available. A new laser test to detect the presence of malaria parasites in the blood was developed in 2002, but is still under clinical study.

Two new techniques to speed the laboratory diagnosis of malaria show promise as of late 2002. The first is acridine orange (AO), a staining agent that works much faster (310 minutes) than the traditional Giemsa stain (4560 min) in making the malaria parasites visible under a microscope. The second is a bioassay technique that measures the amount of a substance called hista-dine-rich protein II (HRP2) in the patient's blood. It allows for a very accurate estimation of parasite development. A dip strip that tests for the presence of HRP2 in blood samples appears to be more accurate in diagnosing malaria than standard microscopic analysis.

Anyone who becomes ill with chills and fever after being in an area where malaria exists must see a doctor and mention their recent travel to endemic areas. A person with the above symptoms who has been in a high-risk area should insist on a blood test for malaria. The doctor may believe the symptoms are just the common flu virus. Malaria is often misdiagnosed by North American doctors who are not used to seeing the disease. Delaying treatment of falciparum malaria can be fatal.

Treatment

Traditional Chinese medicine

The Chinese herb qiinghaosu (the Western name is artemisinin) has been used in China and southeast Asia to fight severe malaria, and became available in Europe in 1994. It is usually combined with another antimalarial drug (mefloquine) to prevent relapse and drug resistance. It is not available in the United States and other parts of the developed world due to fears of its toxicity, in addition to licensing and other issues.

Western herbal medicine

A Western herb called wormwood (Artemesia annua ) that is taken as a daily dose may be effective against malaria. Protecting the liver with herbs like goldenseal (Hydrastis canadensis ), Chinese goldenthread (Coptis chinensis ), and milk thistle (Silybum marianum ) can be used as preventive treatment. These herbs should only be used as complementary to conventional treatment and not to replace it. Patients should consult their doctors before trying any of these medications.

Traditional African herbal medicine

As of late 2002, researchers are studying a traditional African herbal remedy against malaria. Extracts from Microglossa pyrifolia, a trailing shrub belonging to the daisy family (Asteraceae), show promise in treating drug-resistent strains of P. falciparum.

Allopathic treatment

Falciparum malaria is a medical emergency that must be treated in the hospital. The type of drugs, the method of giving them, and the length of the treatment depend on where the malaria was contracted and the severity of the patientís illness.

For all strains except falciparum, the treatment for malaria is usually chloroquine (Aralen) by mouth for three days. Those falciparum strains suspected to be resistant to chloroquine are usually treated with a combination of quinine and tetracycline. In countries where quinine resistance is developing, other treatments may include clindamycin (Cleocin), mefloquin (Lariam), or sulfadoxone/pyrimethamine (Fansidar). Most patients receive an antibiotic for seven days. Those who are very ill may need intensive care and intravenous (IV) malaria treatment for the first three days.

A patient with falciparum malaria needs to be hospitalized and given antimalarial drugs in different combinations and doses depending on the resistance of the strain. The patient may need IV fluids, red blood cell transfusions, kidney dialysis, and assistance breathing.

A drug called primaquine may prevent relapses after recovery from P. vivax or P. ovale. These relapses are caused by a form of the parasite that remains in the liver and can reactivate months or years later.

Another new drug, halofantrine, is available abroad. While it is licensed in the United States, it is not marketed in this country and it is not recommended by the Centers for Disease Control and Prevention in Atlanta.

Expected results

If treated in the early stages, malaria can be cured. Those who live in areas where malaria is epidemic, however, can contract the disease repeatedly, never fully recovering between bouts of acute infection.

Prevention

Preventing mosquito bites while in the tropics is one possible way to avoid malaria. Several researchers are currently working on a malarial vaccine, but the complex life cycle of the malaria parasite makes it difficult. A parasite has much more genetic material than a virus or bacterium. For this reason, a successful vaccine has not yet been developed. A new longer-lasting vaccine shows promise, attacking the toxin of the parasite and therefore lasts longer than the few weeks of those vaccines currently used for malaria prevention. However, as of late 2002, the vaccine had been tested only in animals, not in humans, and could be several years from use.

A newer strategy involves the development of genetically modified non-biting mosquitoes. A research team in Italy is studying the feasibility of this means of controlling malaria.

Malaria is an especially difficult disease to prevent by vaccination because the parasite goes through several life stages. One recent, promising vaccine appears to have protected up to 60% of people exposed to malaria. This was evident during field trials for the drug that were conducted in South America and Africa. It is not yet commercially available.

The World Health Organization has been trying to eliminate malaria for the past 30 years by controlling mosquitoes. Their efforts were successful as long as the pesticide DDT killed mosquitoes and antimalarial drugs cured those who were infected. Today, however, the problem has returned a hundredfold, especially in Africa. Because both the mosquito and parasite are now extremely resistant to the insecticides designed to kill them, governments are now trying to teach people to take antimalarial drugs as a preventive medicine and avoid getting bitten by mosquitoes.

Travelers to high-risk areas should use insect repellant containing DEET for exposed skin. Because DEET is toxic in large amounts, children should not use a concentration higher than 35%. DEET should not be inhaled. It should not be rubbed onto the eye area, on any broken or irritated skin, or on children's hands. It should be thoroughly washed off after coming indoors.

Those who use the following preventive measures get fewer infections than those who do not:

  • Between dusk and dawn, remaining indoors in well-screened areas.
  • Sleep inside pyrethrin or permethrin repellent-soaked mosquito nets.
  • Wearing clothes over the entire body.

Anyone visiting areas where malaria is endemic should take antimalarial drugs starting one week before they leave the United States. The drugs used are usually chloroquine or mefloquine. This treatment is continued through at least four weeks after leaving the endemic area. However, even those who take antimalarial drugs and are careful to avoid mosquito bites can still contract malaria.

International travelers are at risk for becoming infected. Most Americans who have acquired falciparum malaria were visiting sub-Saharan Africa; travelers in Asia and South America are less at risk. Travelers who stay in air conditioned hotels on tourist itineraries in urban or resort areas are at lower risk than those who travel outside these areas, such as backpackers, missionaries, and Peace Corps volunteers. Some people in Western cities where malaria does not usually exist may acquire the infection from a mosquito carried onto a jet. This is called airport or runway malaria.

A 2002 report showed how efforts in a Vietnamese village to approach prevention from multiple angles resulted in a significant drop in malaria cases. Health workers distributed bednets treated with permethrin throughout the village and also made sure they were resprayed every six months. They also worked to ensure early diagnosis, early treatment, and annual surveys of villagers to bring malaria under control.

Resources

BOOKS

Desowitz, Robert S. The Malaria Capers: More Tales of Parasites and People, Research and Reality. New York: W.W. Norton, 1993.

"Extraintestinal Protozoa: Malaria." Section 13, Chapter 161 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. White-house Station, NJ: Merck Research Laboratories, 1999.

Stoffman, Phyllis. The Family Guide to Preventing and Treating 100 Infectious Illnesses. New York: John Wiley & Sons, 1995.

PERIODICALS

Ambroise-Thomas P. "[Curent Data on Major Novel Anti-malarial Drugs: Artemisinin (qinghaosu) derivatives]". [Article in French]. Bulletin of the Academy of National Medicine 183, no.4 (1999): 797780. Abstract.

Causer, Louise M, et al. "Malaria SurveillanceUnited States, 2000". Morbidity and Mortality Weekly Report (July 12, 2002): 915. Abstract.

Coluzzi, M., and C. Costantini. "An Alternative Focus in Strategic Research on Disease Vectors: The Potential of Genetically Modified Non-Biting Mosquitoes." Parassitologia 44 (December 2002): 131135.

"Combination Approach Results in Significant Drop in Malaria Rates in Viet Nam." TB & Outbreaks Week (September 24, 2002): 17. Abstract.

Devi, G., V. A. Indumathi, D. Sridharan, et al. "Evaluation of ParaHITf Strip Test for Diagnosis of Malarial Infection." Indian Journal of Medical Science 56 (October 2002): 489494.

Keiser, J., J. Utzinger, Z. Premji, et al. "Acridine Orange for Malaria Diagnosis: Its Diagnostic Performance, Its Promotion and Implementation in Tanzania, and the Implications for Malaria Control." Annals of Tropical Medicine and Parasitology 96 (October 2002): 643654.

Kohler, I., K. Jenett-Siems, C. Kraft, et al. "Herbal Remedies Traditionally Used Against Malaria in Ghana: Bioassay-Guided Fractionation of Microglossa pyrifolia (Asteraceae)." Zur Naturforschung 57 (November-December 2002): 10221027.

Krudsood, S., K. Buchachart, K. Chalermrut, et al. "A Comparative Clinical Trial of Combinations of Dihydroartemisinin Plus Azithromycin and Dihydroartemisinin Plus Mefloquine for Treatment of Multidrug-Resistant Falciparum Malaria." Southeast Asian Journal of Tropical Medicine and Public Health 33 (September 2002): 525531.

"Laser-based Malaria Test could be Valuable." Medical Devices & Surgical Technology Week (September 22, 2002):4.

Mack, Alison. "Collaborative Efforts Under Way to Combat Malaria." The Scientist 10 (May 12, 1997): 1, 6.

McClellan, S. L. "Evaluation of Fever in the Returned Traveler." Primary Care 29 (December 2002): 947969.

"Multilateral Initiative on Malaria to Move to Sweden." TB & Outbreaks Week (September 24, 2002): 17.

Noedl, H., C. Wongsrichanalai, R. S. Miller, et al. "Plasmodium falciparum : Effect of Anti-Malarial Drugs on the Production and Secretion Characteristics of Histidine-Rich Protein II." Experimental Parasitology 102 (November-December 2002): 157163.

"Promising Vaccine May Provide Long-Lasting Protection." Medical Letter on the CDC & FDA (September 15, 2002): 14.

Stauffer, W. M., D. Kamat, and P. F. Walker. "Screening of International Immigrants, Refugees, and Adoptees." Primary Care 29 (December 2002): 879905.

Thang, H. D., R. M. Elsas, and J. Veenstra. "Airport Malaria: Report of a Case and a Brief Review of the Literature." Netherlands Journal of Medicine 60 (December 2002): 441443.

ORGANIZATIONS

Centers for Disease Control Malaria Hotline. (770) 3324555.

Centers for Disease Control Travelers Hotline. (770) 3324559.

OTHER

Malaria Foundation. http://www.malaria.org.

Mai Tran

Teresa G. Odle

Rebecca J. Frey, PhD

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Malaria

MALARIA

Malaria is the most clinically important parasitic disease worldwide. It kills as many as 2.7 million people annually. The human suffering and economic costs are enormous. Although malaria has been eradicated from temperate zones, it continues to pose a major public health threat to more than forty percent of the world's population.

EPIDEMIOLOGY AND TRANSMISSION

Currently, malaria occurs in one hundred countries and territories inhabited by a total of 2.4 billion people (see Figure 1). The World Health Organization estimates that there are 300 million to 500 million clinical cases annually, resulting in approximately 1.5 million to 2.7 million deaths. Ninety percent of the deaths are in children under five years of age living in sub-Saharan Africa. Other risk groups include pregnant women, internally displaced persons and refugees, and international travelers.

Malaria transmission occurs by the bite of an infective female Anopheles sp. mosquito. Although most cases are transmitted by mosquito, the infection can be passed from mother to the unborn child, or through contaminated blood products, needle sharing, or organ transplantation.

AGENT AND LIFE CYCLE

Human malaria infection is caused by one or more of four species of the intracellular parasite of the genus plasmodium. Plasmodium falciparum, P. vivax, P. ovale, and P. malariae differ in geographic distribution, microscopic appearance, clinical characteristics, and potential for conferring immunity in the host. Although P. vivax is the most common form of malaria worldwide, P. falciparum is the most severe, contributing to most of the morbidity and mortality.

The life cycle of the four species of human malaria consists of two phases: the sexual (sporogony) and asexual phases (schizogony; see Figure 2). Schizogony begins when an infective female anopheline mosquito injects sporozoites into the human host while taking a blood meal. The sporozoite stage of the parasite disappears from circulation within thirty minutes. Those avoiding the host immune system invade the liver and undergo development and multiplication to form schizonts. Over the next five to fifteen days, the schizonts mature, rupture the liver cell, and invade the circulation as merozoites. These merozoites bind to the red blood cell wall. They then penetrate the red blood cell, where they develop as ring forms and grow into trophozoites. Further division creates red blood cell merozoites which form a mature schizont. The blood cell swells and ruptures, releasing merozoites that go on to invade other red blood cells. Clinical symptoms result when the blood cell ruptures and releases cellular debris from infected cells into the bloodstream. The host response to these toxins produces the

Figure 1

classic paroxysms of fever and chills, which are closely timed with the cycles of red blood cell schizogony. The timing of the blood cell phase differs depending on the species of the parasite. P. vivax and P. ovale classically have cycles of forty-eight hours, P. malariae seventy-two hours, and P. falciparum forty-eight hours, although this may vary.

After a period of time, some of the merozoites develop into male and female sexual forms called gametocytes. The gametocytes are ingested by the female anopheline mosquito during a blood meal. Inside the mosquito's stomach, the male and female gametocyte fuse to form a zygote, which quickly becomes a mobile oökinete, which penetrates the stomach wall to form an oöcyst. The oöcyst then bursts, releasing sporozoites that migrate to the salivary glands, ready to be injected into a human host, thus completing the cycle. The parasite generally develops within the mosquito (sporogony) in nine to twelve days, but this time varies according to parasite species and external temperature.

P. vivax and P. ovale differ from the other two species in that some hepatic trophozoites, called hypnozoites, may remain dormant and persist in the liver for months to up to four years. Periodic release of merozoites formed from these hypnozoites can produce recurrent parasitemia and clinical symptoms. Recurrent parasitemia can also occur with P. falciparum and P. malariae, although these species do not form hypnozoites. Infection with these parasites may remain in the blood at subclinical levels because of either the host immune system or use of antimalarial drugs

Figure 2

that do not completely clear the blood-stage parasites. The level of parasitemia can increase weeks to months later, giving rise to another clinical attack. While P. falciparum rarely returns more than several months after the initial infection, P. malariae may become active again up to forty years after the infection.

CLINICAL DISEASE AND DIAGNOSIS

The clinical presentation of malaria is very nonspecific. The degree of natural and acquired immunity of the patient can influence the clinical course dramatically. Classic symptoms among nonimmune persons include fever, chills, sweats, body aches, headache, decreased appetite, nausea, vomiting, and diarrhea. Signs of malaria infection may include an enlarged liver and spleen, anemia, jaundice, low blood pressure, fast heart rate, and decreases in the number of white blood cells and platelets. Children may also show fretfulness, unusual crying, and sleep disturbances. The hallmark of malaria is the paroxysms (attacks) of these symptoms, which recur with predictable periodicity. P. vivax and P. ovale malaria classically cause symptoms every forty-eight hours, P. malariae every seventy-two hours. P. falciparum features irregular patterns. The presentation of these classic attacks is highly variable and may not occur at all early in the disease or in partially immune persons.

Life-threatening disease generally occurs only with P. falciparum infections and can progress from uncomplicated malaria within hours. Neurologic manifestations are the most common presentation of severe disease, often appearing as altered mental status, drowsiness, coma, or convulsions. Other important severe clinical conditions include renal failure, pulmonary distress, severe anemia, low blood sugar, and shock.

Malaria in pregnancy can have devastating effects, especially when caused by P. falciparum. In nonimmune pregnant women, malaria infections can lead to increased risk of maternal and fetal death. Among semi-immune pregnant women, low birth weight due to placental parasitemia represents the greatest risk factor for neonatal death.

Due to the nonspecific nature of malaria symptoms, the diagnosis cannot be made based on clinical signs and symptoms alone. Laboratory diagnostic tests must be performed on any patient suspected of having a malaria infection. The standard for diagnosing malaria is the microscopic visualization of parasites in red blood cells on Giemsa-stained thick and thin smears. Advantages of microscopy include high sensitivity and specificity among properly trained and supervised technicians. Microscopy also offers the ability to identify the infecting species and quantify the level of parasitemia. Immunochromatographic rapid diagnostic tests have been developed that may detect P. falciparum and nonP. falciparum infections. These require no special equipment and are relatively easy to use. The determination of parasite density is not possible with these dipsticks. Other less common methods used for diagnosing malaria infections include serologic tests using an enzyme-linked immunosorbent assay, radioimmunoassay techniques, and polymerase chain reaction.

TREATMENT

To decrease morbidity and mortality from malaria infections, early diagnosis and prompt treatment with an efficacious drug are important. Unfortunately, due to the increasing spread and intensification of drug resistance, there is a limited number of drugs available to prevent and treat malaria.

Chloroquine has long been the mainstay first-line therapy for uncomplicated P. falciparum infection used by malaria control programs; however, resistance to it now exists in most parts of the world. Sulfadoxine-pyrimethamine (SP) has replaced chloroquine in many countries. Resistance to SP has developed in Southeast Asia, parts of South America, and now in certain sites in sub-Saharan Africa. Other drugs commonly used for falciparum infections include quinine, quinidine, amodiaquine, mefloquine, halofantrine, artemisinin compounds, atovaquone, tetracycline, and clindamycin.

Chloroquine is the main drug used for infections with P. vivax, P. ovale, and P. malariae ; however, there are reports of chloroquine-resistant P. vivax in parts of Oceania. Primaquine is used to eliminate the hypnozoites in P. vivax and P. ovale infections.

CONTROL MEASURES

Four basic elements of an effective malaria control program include case management, selective and sustainable preventive measures, early detection of epidemics, and the strengthening of local capacity. Appropriate case management is imperative to malaria control programs. It consists of accurate diagnosis followed by rapid, effective treatment. The detection of malaria in children and pregnant women is especially important. Knowledge of mosquito behavior and relevant environmental, social, and economic features is extremely important for malaria prevention programs. These programs often consist of personal protection (e.g., repellents, insecticide-impregnated bednets), chemoprophylaxis (chemical agent to prevent malaria) for travelers or other high-risk persons, and selective mosquito control (e.g., insecticides, larvicides, environmental management). Malaria epidemics can occur when a community with little or no immunity moves into an area of intense malaria transmission. Epidemics often take place in times of socio-political instability (e.g., complex humanitarian emergencies). These may result in high numbers of deaths. Finally, to be able to control transmission, malaria-endemic countries need to integrate control efforts into the national health plan, strengthen in-country scientific capacity to perform malaria research, and mobilize community support for intervention programs.

John R. MacArthur

S. Patrick Kachur

(see also: Communicable Disease Control; Vector-Borne Diseases )

Bibliography

Bloland, P. B.; Lacritz, E. M.; Kazembe, P. N. et al. (1993). "Beyond Chloroquine: Implications of Drug Resistance for Evaluating Malaria Therapy Efficacy and Treatment Policy in Africa." Journal of Infectious Diseases 167:932937.

Bruce-Chwatt, L. J. (1986). Chemotherapy of Malaria. Geneva: World Health Organization.

Gilles, H. M., and Warrell, D. A. (1993). Bruce-Chwatt's Essential Malariology, 3rd edition. London: Arnold.

Kachur, S. P., and Bloland, P. B. (1998). "Malaria." In Maxcy-Rosenau-Last's Public Health and Preventive Medicine, 14th edition, ed. R. B. Wallace. Stamford, CT: Appleton & Lange.

MacArthur, J. R.; Williams, H. A.; and Bloland, P. B. (2000). "Malaria in Complex Humanitarian Emergencies." Refuge 18(5):411.

Nwanyanwu, O. C.; Ziba, C.; MacHeso, A.; and Kazembe, P. (2000). "Efficacy of Sulphadoxine-pyrimethamine for Acute Uncomplicated Malaria Due to Plasmodium falciparum in Malawian Children under Five Years Old." Tropical Medicine and International Health 5:355358.

White, N. J. (1996). "The Treatment of Malaria." New England Journal of Medicine 335:800806.

World Health Organization (1993). A Global Strategy for Malaria Control. Geneva: Author.

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Malaria

Malaria

Malaria is one of the oldest known infections. It is also the world's most deadly tropical parasitic disease. It kills more people than any other communicable disease except tuberculosis. The disease was first described in ancient Sanskrit and Chinese documents. Hippocrates also described the disease in his writings. It is believed that the army of Alexander the Great was wiped out by the disease during its march across India.

Malaria is thought to have been introduced into the United States by European colonists and African slaves in the sixteenth and seventeenth centuries. It is now endemic in ninety-two countries worldwide. With approximately 41 percent of the world's population at risk, the disease poses a serious health threat globally. As many as two million people die annually; half of the deaths occur in children under five years of age. According to the World Health Organization, this amounts to one child dying every thirty seconds.

Malaria is characterized by both acute and relapsing infection in humans. Hallmark symptoms include periodic episodes of chills and fever, spleen enlargement, and anemia . The disease is caused by microscopic onecelled organisms called sporozoa , which belong to the genus Plasmodium. These parasites are transmitted to humans by several species of anopheles mosquitoes. Malaria is also found in apes, monkeys, birds, bats, reptiles, and rodents. While humans can be infected only by Anopheles mosquitoes, birds and other animals are known to have become ill after being bitten by mosquitoes from the genus Culex.

Four species of Plasmodium are known to cause human malaria: P. falciparum, P. vivax, P. malariae, and P. ovale. Diagnosis can be determined by a blood smear. The most common type, P. falciparum, requires relatively high environmental temperatures for development and is usually found in tropical areas such as western Africa. P. vivax malaria accounts for 43 percent of all cases and is widespread globally. It is known to occur even in cold-winter areas of Korea, Manchuria, and south Russia. The less common P. malariae malaria occurs in about 7 percent of all cases and is confined to the Mediterranean, while P. ovale malaria is rather rare and isolated within a small area of eastern Africa and the islands of the western Pacific.

Malarial attacks typically last four to ten hours during which a person experiences successive stages of chills, high fever, severe headache, and then profuse sweating. Between attacks, body temperature may be normal. The intervals between attacks are usually either forty-eight hours or seventy-two hours. The first attack typically occurs seven to nine days after a person is bitten by a disease-carrying mosquito.

Mosquito Transmission

Though malaria can occur in temperate regions, it is most common in the tropics and subtropics, where climatic conditions favor mosquito development. Mosquitoes lay their eggs in water where larvae mature and hatch into flying adults. Newly hatched female mosquitoes are especially bloodthirsty and require a blood meal to produce fertile eggs. When these mosquitoes bite a human who is already infected, they ingest the malarial parasite and the disease transmission cycle begins.

The life cycle of the Plasmodium starts in the stomach of the female mosquito. The organism's double life cycle has two phasesa sexual reproductive cycle and an asexual reproductive cycle. While the parasite is in its asexual, free-swimming stage, it is known as a sporozoite . When an infected mosquito bites, the sporozoite is injected along with saliva into the human bloodstream.

Once inside the bloodstream, the sporozoite enters a red blood cell. Inside the red blood cell, it changes shape and divides into smaller forms called merozoites . The red blood cell containing these merozoites ruptures, releasing them into the blood. The merozoites infect other red blood cells, and the life cycle is repeated. The rupturing of red blood cells causes the symptoms of fever and chills.

A mosquito biting an infected host at this stage can ingest merozoites. If this happens, the merozoites enter the mosquito's stomach and become male and female gametocytes . This kicks off a sexual reproductive life cycle where the separate male and female gametocytes unite together to form a single-celled zygote . This zygote grows to become an oocyst or large egglike sac, which eventually divides, releasing a multitude of asexual, freeswimming sporozoites.

These sporozoites move to the mosquito's head and salivary glands from which they can be injected into a human during the mosquito's next bite. This asexual cycle is repeated. During the asexual life cycle, the parasites grow and divide synchronously. The resulting merozoites produce the regularly occurring fever and chill attacks that are typical of malaria.

Early Cases and Treatments

The first documented treatment of the disease occurred in 1630 when "Jesuit's bark," from a cinchona tree, was used to ease the fever of a Spanish magistrate in Peru. Amazingly, the magistrate recovered and eventually the substance quinine was isolated from the bark and processed commercially as a treatment. The Cinchona genus includes about forty species of plants, mostly trees, native to the Andes of South America. Certain species are also known to grow in India and Sri Lanka.

In the 1940s, the antimalarial drug chloroquine was introduced as an effective additional treatment. Chloroquine is a member of an important series of chemically related antimalarial agents, the quinoline derivatives. A global eradication program was initiated in the 1950s and 1960s by the World Health Organization (WHO), in Geneva, Switzerland, which led to a significant decrease in malaria cases in Asia and South America.

Drug Resistant Strains and Reemergence of Disease

Drug resistant strains of malaria began to emerge in the 1970s, making the disease harder to control. During the 1990s the prevalence of malaria escalated at an alarming rate, especially in Africa where control efforts have typically been piecemeal and uncoordinated. Additionally, the phenomenon of "airport malaria," or the importing of malaria by international travelers, is becoming commonplace. Persons who are not normally exposed to this mosquito in its natural habitat can acquire "airport malaria" through the bite of an infected mosquito that has traveled far from its home.

In one study, random searches of airplanes at Gatwick Airport in London found dozens of airplanes from tropical countries containing mosquitoes. After a mosquito leaves an aircraft, it may survive long enough to take a blood meal and transmit the disease, usually in the vicinity of the airport. Incidents of malaria transmitted this way are expected to become more common, since airport travel has increased by almost 7 percent a year since 1980 and is predicted to increase by 5 percent a year for the first twenty years of the twenty-first century.

Resurgence and increased risk of the disease appears to be linked to several factors. Changes in land use, such as mining, logging, and agricultural projects, particularly in the Amazon and Southeast Asia frontier area, are providing new mosquito breeding sites. Other reasons for the disease's spread include global climatic changes, disintegration of health services, armed conflicts, and mass movements of refugees into areas of high malaria transmission.

Reemergence of malaria through mobility occurred in Brazil, for example. Malaria had been practically eradicated from most areas of the Amazon region until massive population movements began to colonize new territories. New highways were built, linking the Amazon to the rest of the country and attracting laborers to work on road construction. In 1970, prior to new road construction in these new areas, there were approximately 50,000 cases of malaria reported; by 1990, reports had increased to more than 500,000, representing 10 percent of the world's reported cases outside Africa.

As a result of the explosion of international travel, imported cases of malaria are now showing up more in developed countries such as the United States Malaria is also reemerging in areas where it was previously under control or eradicated, such as in Korea. According to the WHO, global warming and other climatic events such as El Niño also play a role in increasing the disease. Malaria has now spread to highland areas of Africa, where El Niño effects such as increased rainfall have influenced mosquito breeding sites and hence the transmission of the disease. The emergence of multidrug-resistant strains of parasites is also exacerbating the situation.

Disease Prevention

Prevention of malaria encompasses a variety of measures. Some may protect against infectionthese are directed against mosquitoeswhereas others focus on stopping the development of the disease in human beings. Although only a limited number of drugs are available, if these are used properly and targeted to those at greatest risk, malaria can be reduced.

Since the early 1990s, considerable progress has been made in the search for a malaria vaccine. More than a dozen candidate vaccines are currently in development; some of them are in clinical trials. An effective vaccine could be available within the first twenty years of the twenty-first century. In the meantime, there are a number of prescription drugs available on the market in developed countries that can help prevent malaria, especially in individuals traveling to high incidence areas. Some of the best-known preventatives include Mefloquine, Malarone, and Primaquine.

Medical researchers continue to discover new drug therapies. Most recently, Chinese scientists discovered a drug called artemether that is derived from the Chinese herb qinghaosu. The new drug appears to be as effective as quinine although much slower acting. It may even kill resistant strains of malaria.

see also Interspecies Interactions; Parasitism.

Stephanie A. Lanoue

Bibliography

Noble, Elmer R., Glenn A. Noble, Gerhard A. Schad, and Austin J. MacInnes. Parasitology. London: Lea & Febiger, 1989.

Turkington, Carol, and Bonnie Ashby. Encyclopedia of Infectious Disease. New York: Facts on File, Inc., 1998.

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Malaria

MALARIA

MALARIA is a disease characterized by chills and fever that recur at regular intervals, anemia, and an enlarged spleen. It is caused by four species of Plasmodium, a protozoan. Long prevalent in Europe and Africa, malaria was probably brought to the Americas by colonists and slaves. By 1700 it had become established from South Carolina to New England. Malaria spread into the Mississippi Valley with the American settlers, where it became a commonly accepted part of life. Generally chronic and debilitating to all ages and often fatal, it placed a heavy burden of ill health on settlers, especially along the waterways that formed the chief routes of commerce.

Malaria reached its height in New England in the eighteenth century and after 1800 appeared only sporadically. In the Midwest it reached its peak about 1875, declining


thereafter quite rapidly in the north. Associated with marshes, malaria in the United States tended to rise with the initial clearing of land and to fall with cultivation and drainage, as Benjamin Rush noted in 1785. Better housing and the development of railroads moved settlement out of the river bottoms, contributing to the decline of malaria.

Cinchona bark, used to treat malaria, was brought to Europe in the 1630s from Peru, and by the eighteenth century was widely used, although often incorrectly. Well into the nineteenth century, American doctors also relied on bloodletting and cathartics. The isolation of quinine by French chemists in 1820 made treatment more practicable, and from the 1850s, quinine was also used to prevent malaria from developing. In 1880 a French army surgeon, Alphonse Laveran, demonstrated the parasitic cause of the disease in the blood of humans. Dr. A. F. A. King of Washington, D.C., correctly speculated on its transmission by mosquito in 1882, and William George MacCollum added significantly to knowledge of the complex life history of the plasmodium in 1897. British physician Ronald Ross made the crucial demonstration of mosquito transmission in 1898. Using anti-mosquito measures and prophylactic quinine, William C. Gorgas in 1901 initiated a campaign that reduced the malaria rate in Havana from 909 per 1,000 in 1899 to 19 per 1,000 in 1908. Later he obtained comparable results in the Canal Zone, which made possible the building of the Panama Canal.

A decline in antimalaria programs in the 1920s, followed by the depression, led in the early 1930s to a resurgence of the disease in the United States, which was curbed under New Deal relief programs. During World War II, both the Public Health Service and the army increased antimalaria programs in the United States, while overseas actions brought home the global importance of the disease. After the war, the Public Health Service, using the newly developed insecticide DDT, inaugurated a program to eradicate malaria in the United States. In 1935, there were about 4,000 malaria deaths in the country, in 1945 about 400, and by 1952 only 25. Since World War II the United States has also participated in anti-malaria campaigns in other countries. Although these efforts have greatly reduced the incidence of malaria, it remains a major health problem in many of the less developed countries.

BIBLIOGRAPHY

Ackerknecht, Erwin Heinz. Malaria in the Upper Mississippi Valley, 1760–1900. Baltimore: John Hopkins Press, 1945; New York: Arno Press, 1977.

Jaramillo-Arango, Jaime. The Conquest of Malaria. London: W. Heinemann, 1950.

Russell, Paul Farr. Man's Mastery of Malaria. London, New York: Oxford University Press, 1955.

Shuler, Alexandria V. Malaria: Meeting the Global Challenge. Boston: Oelgeschlager, Gunn, and Hain, 1986.

John B.Blake/h. s.

See alsoEpidemics and Public Health ; "Silent Spring."

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malaria

malaria, infectious parasitic disease that can be either acute or chronic and is frequently recurrent. Malaria is common in Africa, Central and South America, the Mediterranean countries, Asia, and many of the Pacific islands. In the United States it was found in the South and less frequently in the northern and western parts of the country.

Plasmodium falciparum is the most deadly of all the five Plasmodium parasites that typically cause malaria in humans. All the species require both the Anopheles mosquito and humans to complete the life cycle. Sexual reproduction of the protozoans occurs in the mosquito; an immature form is then transmitted to the human via the bite of the mosquito. In a person the parasite goes to the liver, replicates, and moves into the bloodstream, where it attacks red blood cells for their hemoglobin. Some of the plasmodia become sexually mature and are transmitted back to another biting mosquito. P. knowlesi, however, is primarily transmitted from monkeys to humans via mosquitoes.

Symptoms

At the onset of malaria, bouts of chills (ague) and fever lasting several hours and occurring every three or four days are the usual symptoms. If the disease is not treated, the spleen and the liver become enlarged, anemia develops, and jaundice appears. Death may occur from general debility, anemia, or clogging of the vessels of cerebral tissues by affected red blood cells. Cerebral malaria is most commonly seen in infants, pregnant women, and nonimmune travelers to endemic areas.

Immune Response

P. falciparum creates protein knobs on the surfaces of the red blood cells it attacks. These knobs attach the cell to the lining of the blood vessel, preventing its removal to the spleen for destruction. The parasite slows detection by the immune system by changing the makeup of the knobs periodically, substituting or rearranging its 150 "var" (variability) genes, a strategy unique to malaria. A pattern of remission and relapse results as the immune system learns each new "code" only to have it again changed. Patients with malaria gradually do develop immunity that modifies the course of the disease, but this immunity has a degree of strain specificity. Some of the Plasmodium species have the ability to persist in the liver and cause a new infection years after the original one.

Treatment and Control

The bark of the cinchona and its product, quinine, have been used in the treatment of malaria for centuries. After World War II, they were largely replaced by the synthetic analog chloroquine. The use of chloroquine, in addition to the use of DDT for mosquito control, was expected to eradicate the disease, but a World Health Organization campaign (1955–69) to eradicate the disease globally (by controlling mosquitoes long enough to allow the human population to become disease free) proved unsuccessful. Despite that, spraying successfully eradicated the disease in some areas (Sardinia, Japan, and Taiwan). In the United States, the disease, which had been endemic in many SE states, was eradicated in 1951.

In the 1960s several strains of the malarial parasite developed resistance to chloroquine. This, plus the growing immunity of mosquitoes to insecticides, caused malaria to become one the of world's leading re-emerging infectious diseases, infecting some 225 million people a year and killing more than 650,000 in 2010. Those numbers may be significant underestimates. By 2010, however, the number of infections was again falling due to improved malaria control in Africa.

Mefloquine may be used in areas where the disease has become highly resistant to chloroquine, but some strains are now resistant to it and other drugs. Artemisinin (derived from sweet wormwood) in combination with other drugs is now in many cases the first-line treatment in many cases, but resistance to it also has developed, in parts of SE Asia. Amodiaquine in combination with sulfadoxine and pyrimethamine has also been shown to be effective, and malarone (atovaquone and proguanil) also is used for resistant strains. The use of combinations of drugs with different modes of actions increases the effectiveness of treatment and helps reduce the development of drug resistance.

Vaccines against malaria remain experimental. Spraying is still used to control malaria-transmitting mosquitoes, and more recently the use of mosquito nets treated with a long-lasting insecticide has become widespread. Fish that feed on mosquito larvae also have been employed to control mosquitoes.

See studies by M. Humphreys (2001), S. Shah (2010), B. Shore (2010), and R. M. Packard (2011).

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malaria

malaria (ague, marsh fever, periodic fever, paludism) (mă-lair-iă) n. an infectious disease due to the presence of parasitic protozoa of the genus Plasmodium within the red blood cells. The disease is transmitted by the Anopheles mosquito and is confined mainly to tropical and subtropical areas. After an incubation period varying from 12 days to 10 months parasites invade, multiply within, and eventually destroy the red blood cells, releasing new parasites. This causes a short bout of shivering, fever, and sweating, and the loss of healthy red cells results in anaemia. When the next batch of parasites is released symptoms reappear. The interval between fever attacks varies in different types of malaria. Preventive and curative treatment relies on such drugs as chloroquine and proguanil. benign m. malaria caused by P. vivax, P. malariae, or P. ovale, with intervals of 2–3 days between fever attacks. falciparum (or malignant) m. the most severe form of malaria, in which the interval between fever attacks varies from a few hours to 2 days.

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Malaria

MALARIA

DEFINITION


Malaria is a serious, infectious disease spread by certain kinds of mosquitoes. It is common in tropical climates and is characterized by chills, fevers, and an enlarged spleen. These symptoms reappear again and again. The disease can be treated with medication, but it tends to come back even after being cured. Malaria is endemic in many developing countries. An endemic disease is one that occurs frequently in a particular location. Isolated, limited outbreaks of malaria sometimes occur in the United States.

DESCRIPTION


Malaria is not a serious problem in the United States. Over the past ten years, only about 1,200 cases have been reported each year in this country. In most cases, a person was infected outside the United States while traveling on business or on vacation.

Malaria is a far more serious problem in other parts of the world. Between 300 million and 500 million people in Africa, India, Southeast Asia, the Middle East, the South Pacific, and Central and South America have the disease. About two million people die of the disease every year. Most of these deaths occur in southern Africa.

A person can have malaria more than once. In some parts of Africa, people have up to forty bouts of malaria during their lifetime. Malaria is becoming a more serious problem because the organisms that cause the disease are growing resistant to the drugs used to treat it.

CAUSES


Malaria is caused by four different kinds of parasites belonging to the plasmodium family. A parasite is an organism that lives off another organism. Animals can also get malaria, but malaria cannot be passed from humans to animals or from animals to humans.

Malaria is transmitted by female mosquitoes that carry the parasite in their bodies. When the mosquito bites a human, it injects a small amount of its saliva into the human's bloodstream. The saliva contains parasites that travel through the person's bloodstream to his or her liver. There, the parasites reproduce. Eventually, they leave the liver and travel back into the bloodstream. Once in the bloodstream, they begin to cause the symptoms of malaria.

Malaria cannot be passed directly from one human to another. It can be transmitted by a mosquito. A mosquito may bite a person infected with the malaria parasite. When it sucks the person's blood, it takes in some of the parasites. If the same mosquito bites a second person, it may transfer those parasites to the uninfected person.

Malaria can also be transmitted through blood transfusions. If an infected person donates blood, the blood will contain malaria parasites. If the blood is put into another person's body, the parasites will also flow into his or her bloodstream. For this reason, blood donors are often screened for the malaria parasite before they are allowed to give blood.

The incubation period for malaria varies considerably. An incubation period is the time between the mosquito bite and the time symptoms of malaria begin to appear. The incubation period differs depending on the kind of parasite involved. For the most serious form of malaria, the incubation period is eight to twelve days. In some rare forms of malaria, the incubation period can be as long as ten months.

Malaria: Words to Know

Artemisinin:
An antimalarial herb used for many years in China under the name qiinghaosu.
Chloroquine:
An antimalarial drug first used in the 1940s as a substitute for quinine, and still widely used in Africa because of its relatively low cost.
Mefloquine:
An antimalarial drug developed by the U.S. Army in the early 1980s.
Quinine:
One of the first successful treatments for malaria, derived from the bark of the cinchona tree.
Sulfadoxine/pyrimethamine (trade name Fansidar):
An antimalarial drug developed in the 1960s, often used in areas where quinine and chloroquine are no longer effective.

SYMPTOMS


A person infected with malaria passes through three stages of very distinctive symptoms. The first stage is characterized by uncontrollable shivering for an hour or two. In the next stage, the patient's temperature rises quickly. It may reach 106°F (41°C) for a period of up to six hours. In the third stage, the patient begins to sweat profusely, and his or her temperature drops rapidly.

Other symptoms may accompany these stages. They include fatigue, severe headache, nausea, and vomiting. After the third stage, the patient often falls asleep from exhaustion.

The three stages are often repeated the following day, two days later, or at some later time. In many cases, a person experiences a repetition of the stages again and again during their lifetime. Some people go many years before the symptoms repeat.

The most serious forms of malaria can result in death in a matter of hours. The parasites attack a person's red blood cells and change their structure. The cells become very sticky and begin to clump together. As they do, they may block blood vessels in vital organs, such as the kidneys and spleen. These organs may no longer be able to function properly, and the patient may fall into a coma and die.

DIAGNOSIS


Malaria can be diagnosed with a blood test. A sample of a patient's blood is taken and studied under a microscope to detect the presence of parasites. Blood tests sometimes need to be repeated after a seventy-two-hour period to confirm the diagnosis.

The three stages of malaria can also be used to diagnose the disease. A person who lives in an area where malaria is common and who has chills, fever, and a very high temperature should have a blood test as quickly as possible.

Malaria is sometimes misdiagnosed in North America. The disease is not very common in this part of the world, and its symptoms are similar to those of the flu (see influenza entry). A doctor may think that a person has the flu when he or she really has malaria. This kind of misdiagnosis can result in the patient's death if he or she has a severe case of malaria.

AN ANCIENT ILLNESS

Malaria has been a known disease for centuries and was described in medical records from ancient China, India, and Greece. Doctors first believed that malaria was caused by poisonous vapors in the air. People who lived around swamps, bogs, and other wetlands were especially likely to get the disease. Therefore, it was presumed that it must be the "bad gases" given off by these watery regions. In fact, the name of the disease comes from two Italian words for "bad air": mal- ("bad") and -aria ("air").

The Romans are credited with one of the most successful attempts to eliminate malaria. They drained large areas of swampy land around the city, believing that they were cutting off the supply of "bad gases." In fact, they were destroying the wet areas in which malaria carriers (the mosquitoes) lived and bred.

TREATMENT


Malaria can be treated with drugs. However, treatment is complicated by a number of factors. First, each type of malaria requires a different drug. Second, the treatment depends on the region of the world in which the person was infected. The kinds of parasites living in different parts of the world respond in different ways to different drugs.

The classic treatment for malaria is quinine. Quinine is still effective in treating some forms of malaria in some parts of the world, but other parasites have developed a resistance to quinine.

If quinine is not effective, a variety of antibiotics can be tried. These include tetracycline (pronounced tet -ruh-SIE-kleen), clindamycin (pronounced klin-duh-MY-suhn, trade name Cleocin), mefloquine (pronounced MEF-luhkwine, trade name Lariam), or sulfadoxine/pyrimethamine (pronounced sullfuh-DOK-seen/pi-ruh-METH-uh-meen, trade name Fansidar). A modified form of quinine known as chloroquine (pronounced KLOR-uh-kween) can also be used. In some parts of the world, the parasite that causes the most serious form of malaria is resistant to all known drugs.

Patients with very serious cases of malaria may require hospitalization and special treatments. These treatments may include intravenous fluids (fluids injected into the patient's bloodstream), blood transfusions, kidney dialysis, and oxygen therapy to help him or her breathe.

Alternative Treatment

The Chinese herb qinghao (known as artemesia in the West) has long been used to treat malaria. However, it is not approved for use in the United States and other parts of the developed world. Researchers are still concerned about the herb's possibly dangerous side effects.

Some practitioners suggest using certain herbs to protect against malaria and to strengthen the liver. These herbs include wormwood, goldenseal, Chinese goldenthread, and milk thistle.

PROGNOSIS


If treated in its early stages, malaria can be cured. Cures are more difficult for people who live in areas where malaria is endemic. These people may be bitten by mosquitoes and exposed to malaria parasites again and again and may never fully recover from the disease.

PREVENTION


Malaria can be prevented in one of two ways. First, a person can avoid being bitten by a mosquito carrying the malaria parasite. The World Health Organization (WHO) has been working to eliminate malaria for more than thirty years. Its approach has been to kill as many of the mosquitoes that cause malaria as possible. For some years, WHO was quite successful in this effort. It used DDT and other pesticides to kill mosquitoes. Unfortunately, mosquitoes have slowly become resistant to many pesticides. It has become more and more difficult to kill mosquitoes with the pesticides now available.

The second method for avoiding malaria is to take drugs that protect against the disease. These drugs kill parasites as soon as they enter the bloodstream. The problem is that antimalarial drugs are expensive. Most people in Africa, Asia, and other areas where malaria is common cannot afford them.

Scientists have long hoped to find a vaccine for malaria. With a vaccine, a person could be protected for a lifetime with one or a few shots. So far, however, researchers have had no success in producing such a vaccine.

People who travel in areas where malaria is common can protect themselves by wearing mosquito repellent. The compound known as DEET is one of the most effective repellents, but it can have harmful side effects, especially in children. It should be used only with caution.

Certain other preventive measures can also be followed, including:

  • Staying indoors in well-screened areas between dusk and dawn
  • Sleeping inside mosquito nets that have been soaked with mosquito repellent
  • Wearing clothes that cover the entire body

People who plan trips to areas in which malaria is endemic should take antimalarial drugs as a preventive against contracting the disease. The drugs usually prescribed are chloroquine or mefloquine. A person starts taking the drugs a few days before leaving on the trip. He or she continues to take the drugs while on the trip and for at least four weeks after they return home.

FOR MORE INFORMATION


Books

Desowitz, Robert S. The Malaria Capers: More Tales of Parasites and People, Research, and Reality. New York: W. W. Norton, 1993.

Stoffman, Phyllis. The Family Guide to Preventing and Treating 100 Infectious Illnesses. New York: John Wiley & Sons, 1995.

Periodicals

Kristof, Nicholas D. "Malaria Makes a Comeback, Deadlier Than Ever." New York Times (January 8, 1997).

Mack, Alison. "Collaborative Efforts Under Way to Combat Malaria." Scientist (May 12, 1997): p. 1+.

Shell, Ellen Ruppel. "Resurgence of a Deadly Disease." Atlantic Monthly (August 1997).

Organizations

Centers for Disease Control Malaria Hotline. (770) 332-4555.

Centers for Disease Control Travelers Hotline. (770) 332-4559.

Malaria Foundation International. http://www.malaria.org.

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Malaria

Malaria

What Is Malaria?

How Common Is Malaria?

Is Malaria Contagious?

What Are the Signs and Symptoms of Malaria?

How Is Malaria Diagnosed and Treated?

Can Malaria Be Prevented?

Resources

Malaria (mah-LAIR-e-uh) is a disease caused by a parasite that is spread to humans by the bite of an infected mosquito.

KEYWORDS

for searching the Internet and other reference sources

Anopheles mosquito

Chloroquine Mosquito-borne illness

Plasmodium

Quinine

What Is Malaria?

Malaria, which literally means bad air, was once thought to be spread in the air around stagnant marshes. It is now known that mosquitoes, particularly female Anopheles (a-NOH-fel-eez) mosquitoes, spread the parasites that cause malaria. Four different species of a parasite in the genus Plasmodium (plaz-MO-dee-um) cause malaria. They are falciparum (fal-SIP-ar-um), malariae (ma-LAIR-e-eye), ovale (o-VAL-e), and vivax (VIvax). Of the four, P. falciparum is the most common and the most deadly. Plasmodium requires time in both the mosquito vector* and human host* to complete its life cycle.

*vector
(VEK-tor) is an animal or insect that carries a disease-causing organism and transfers it from one host to another.
*host
is an organism that provides another organism (such as a parasite or virus) with a place to live and grow.

How Common Is Malaria?

Forty percent of the worlds population is at risk for contracting malaria from infected mosquitoes, primarily in tropical and subtropical regions. Worldwide, there are 300 to 500 million cases of malaria and more than one million deaths from malaria each year. More than 90 percent of all malaria deaths occur in sub-Saharan Africa, a vast area south of the Sahara Desert, and 75 percent of deaths occur in children. Plasmodium falciparum causes malaria in this region, and poverty, poor nutrition, and poor access to health care all contribute to the high death rate. Malaria is increasingly common in Central and South America, Asia, the Middle East, and the Pacific Islands. About 1,200 cases of malaria are diagnosed in the United States each year, mostly in recent immigrants or travelers from countries where malaria is found.

Mosquito control has virtually eliminated malaria in areas with temperate climates. However, the disease is making a comeback as mosquitoes become resistant to insecticides and Plasmodium becomes resistant to medications used to treat malaria.

Is Malaria Contagious?

Malaria is not passed directly from one person to another. Mosquitoes spread the disease. When a mosquito bites an infected person, it ingests malaria parasites contained in that persons blood. The parasites need an incubation period* of about 1 week in the mosquito before the mosquito can spread the disease when it bites another person. Once in a persons body, the parasites travel to the liver where they can remain dormant, or inactive, for months or even years. In the liver, the parasites grow and multiply and are then ready to move into the bodys red blood cells, where they continue to grow until the red blood cells burst, freeing more parasites to attack more blood cells. The parasite can be ingested by a mosquito and spread to another person only during the time that Plasmodium is in the blood.

*incubation
(ing-kyoo-BAY-shun) period is the time between infection by a germ and when symptoms first appear. Depending on the germ, this period can be from hours to months.

In most of Latin America, Africa, the Middle East, and Asia, people are at a higher risk of getting malaria. Drug-resistant malaria has caused the disease to be on the rise in these parts of the world.

What Are the Signs and Symptoms of Malaria?

Malaria causes fever and symptoms similar to those of the flu. In the early stages of the disease when the parasite is in the liver, the infected person does not feel sick. When the parasites invade the red blood cells and cause them to burst, toxins (poisons that harm the body) are released into the blood and the person experiences fever, chills, sweating, headache, muscle aches, and tiredness. Symptoms typically begin 9 to 16 days after infection with the parasite, but the time may vary depending on the infecting species. Episodes of these symptoms reoccur every 48 to 72 hours. Other symptoms may include nausea (NAW-zee-uh), vomiting, and diarrhea (dye-uh-REE-uh).

How Is Malaria Diagnosed and Treated?

Under the microscope, a blood sample from a person who has malaria will show one of the four species of Plasmodium parasites within the red blood cells. Malaria is treated with antimalarial drugs, many of them derived from quinine, which is found naturally in the bark of the cinchona tree from Peru. Which drug is chosen to treat a patient depends on the parasite causing the infection, the severity of symptoms, the age of the patient, and whether the parasite is resistant to certain drugs. Some patients may need intensive hospital care.

Treatment can last several weeks or months. In some infections, the parasite can remain dormant in the liver for months or years and the disease may return even after treatment. Destruction of red blood cells in cases of malaria can result in anemia* and jaundice*. Severe and untreated infection may cause liver and kidney* problems, seizures*, mental confusion, coma*, and death; malaria is fatal in 1 in 500 cases. Children and pregnant women are particularly vulnerable to complications. Infected pregnant women are at risk for miscarriage*, premature delivery*, and stillbirth*, and anemia in children can have long-term effects on growth and development.

*anemia
(uh-NEE-me-uh) is a blood condition in which there is a decreased amount of oxygen-carrying hemoglobin in the blood and, usually, fewer than normal numbers of red blood cells.
*jaundice
(JON-dis) is a yellowing of the skin, and sometimes the whites of the eyes, caused by a buildup in the body of bilirubin, a chemical produced in and released by the liver. An increase in bilirubin may indicate disease of the liver or certain blood disorders.
*kidney
is one of the pair of organs that filter blood and remove waste products and excess water from the body in the form of urine.
*seizures
(SEE-zhurs) are sudden bursts of disorganized electrical activity that interrupt the normal functioning of the brain, often leading to uncontrolled movements in the body and sometimes a temporary change in consciousness.
*coma
(KO-ma) is an unconscious state in which a person cannot be awakened and cannot move, see, speak, or hear.
*miscarriage
is the ending of a pregnancy through the death of the embryo or fetus before birth.
*premature delivery
is when a baby is born before it has reached full term.
*stillbirth
is the birth of a dead fetus.

Can Malaria Be Prevented?

In areas where malaria is endemic*, people can avoid being bitten by mosquitoes by wearing long-sleeved shirts and long pants, using insect

*endemic
(en-DEH-mik) describes a disease or condition that is present in a population or geographic area at all times.

Scientists, in searching for alternative means of malaria control, have recently been able to genetically modify mosquitoes carrying a form of malaria that affects rodents. The genetically modified mosquitoes were less susceptible to infection after feeding on a malaria-infected mouse and were far less likely than normal mosquitoes to transmit the malaria parasite to other mice. Phototake

repellent, and staying in a screened or air-conditioned room from dusk to dawn when mosquitoes are most active. Bed nets treated with certain insecticides repel mosquitoes for 6 to 12 months. Travelers to foreign countries where malaria is found should take preventive drugs prescribed by a doctor before leaving.

Scientists are working to develop a vaccine that will prevent malaria. However, the different species of Plasmodium and the complicated life cycle of these parasites have made developing a vaccine difficult.

See also

West Nile Fever

Yellow Fever

Resources

Book

Jones, Ann. Looking for Lovedu: Days and Nights in Africa. Knopf: New York, 2001. The authors account of her journey across Africa in search of the legendary Lovedu tribe is full of adventure and complications such as malaria.

Organization

World Health Organization (WHO), Avenue Appia 20, 1211 Geneva 27, Switzerland. WHO provides information about malaria at its website.

Telephone 011-41-22-791-2111 http://www.who.int

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malaria

malaria Parasitic disease resulting from infection with one of four species of Plasmodium protozoan. Transmitted by the Anopheles mosquito, it is characterized by fever and enlargement of the spleen. Attacks of fever, chills, and sweating typify the disease, and recur as new generations of parasites develop in the blood. The original antimalarial drug, quinine, gave way to synthetics such as chloroquine. With 270 million people infected, malaria is one of the most widespread diseases, claiming two million lives a year.

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malaria

ma·lar·i·a / məˈlerēə/ • n. an intermittent and remittent fever caused by a protozoan parasite that invades the red blood cells. The parasite belongs to the genus Plasmodium (phylum Sporozoa) and is transmitted by female mosquitoes of the genus Anopheles. DERIVATIVES: ma·lar·i·al / -ēəl/ adj. ma·lar·i·an / -ēən/ adj. ma·lar·i·ous / -ēəs/ adj.

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malaria

malaria A disease caused by the parasitic protozoan Plasmodium, which requires two hosts, the bloodsucking female Anopheles mosquito and a human, in order to complete its complex life cycle. Symptoms of fever and anaemia in humans are caused by invasion and destruction of the red blood cells during an asexual phase of the life cycle. See Apicomplexa.

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malaria

malaria fever formerly supposed to be caused by exhalations from marshy places. XVIII. — It. mal'aria for mala aria ‘bad AIR’; cf. MAL-.

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malaria

malariabarrier, carrier, farrier, harrier, tarrier •Calabria, Cantabria •Andrea • Kshatriya • Bactria •Amu Darya, aria, Zaria •Alexandria •Ferrier, terrier •destrier •aquaria, area, armamentaria, Bavaria, Bulgaria, caldaria, cineraria, columbaria, filaria, frigidaria, Gran Canaria, herbaria, honoraria, malaria, pulmonaria, rosaria, sacraria, Samaria, solaria, tepidaria, terraria •atria, gematria •Assyria, Illyria, Styria, SyriaLaurier, warrior •hypochondria, mitochondria •Austria •auditoria, ciboria, conservatoria, crematoria, emporia, euphoria, Gloria, moratoria, phantasmagoria, Pretoria, sanatoria, scriptoria, sudatoria, victoria, Vitoria, vomitoria •Maurya •courier, Fourier •currier, furrier, spurrier, worrier •Cumbria, Northumbria, Umbria •Algeria, anterior, bacteria, Bashkiria, cafeteria, criteria, cryptomeria, diphtheria, exterior, hysteria, Iberia, inferior, interior, Liberia, listeria, Nigeria, posterior, Siberia, superior, ulterior, wisteria •Etruria, Liguria, Manchuria, Surya

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Malaria

Malaria


Malaria is a disease that affects hundreds of millions of people worldwide. In the developing world malaria contributes to a high infant mortality rate and a heavy loss of work time. Malaria is caused by the single-celled protozoan parasite, Plasmodium. The disease follows two main courses: tertian (three day) malaria and quartan (four day) malaria. Plasmodium vivax causes benign tertian malaria with a low mortality (5%), while Plasmodium falciparum causes malignant tertian malaria with a high mortality (25%) due to interference with the blood supply to the brain (cerebral malaria). Quartan malaria is rarely fatal.

Plasmodium is transmitted from one human host to another by female mosquitoes of the genus Anopheles. Thousands of parasites in the salivary glands of the mosquito are injected into the human host when the mosquito takes blood. The parasites (in the sporozoite stage) are carried to the host's liver where they undergo massive multiplication into the next stage (cryptozoites). The parasites are then released into the blood stream, where they invade red blood cells and undergo additional division. This division ruptures the red blood cells and releases the next stage (the merozoites), which invade and destroy other red blood cells. This red blood cell destruction phase is intense but short-lived. The merozoites finally develop into the next stage (gametocytes) which are ingested by the biting mosquito.

The pattern of chills and fever characteristic of malaria is caused by the massive destruction of the red blood cells by the merozoites and the accompanying release of parasitic waste products. The attacks subside as the immune response of the human host slows the further development of the parasites in the blood. People who are repeatedly infected gradually develop a limited immunity. Relapses of malaria long after the original infection can occur from parasites that have remained in the liver, since treatment with drugs kills only the parasites in the blood cells and not in the liver. Malaria can be prevented or cured by a wide variety of drugs (quinine, chloroquine, paludrine, proguanil, or pyrimethamine). However, resistant strains of the common species of Plasmodium mean that some prophylactic drugs (chloroquine and pyrimethamine) are no longer totally effective.

Malaria is controlled either by preventing contact between humans and mosquitoes or by eliminating the mosquito vector. Outdoors, individuals may protect themselves from mosquito bites by wearing protective clothing, applying mosquito repellents to the skin, or by burning mosquito coils that produce smoke containing insecticidal pyrethrins. Inside houses, mosquito-proof screens and nets keep the vectors out, while insecticides (DDT) applied inside the house kill those that enter. The aquatic stages of the mosquito can be destroyed by eliminating temporary breeding pools, by spraying ponds with synthetic insecticides, or by applying a layer of oil to the surface waters. Biological control includes introducing fish (Gambusia ) that feed on mosquito larvae into small ponds. Organized campaigns to eradicate malaria are usually successful, but the disease is sure to return unless the measures are vigilantly maintained.

See also Epidemiology; Pesticide

[Neil Cumberlidge Ph.D. ]


RESOURCES

BOOKS


Bullock, W. L. People, Parasites, and Pestilence: An Introduction to the Natural History of Infectious Disease. Minneapolis: Burgess Publishing Company, 1982.

Knell, A. J., ed. Malaria: A Publication of the Tropical Programme of the Wellcome Trust. New York: Oxford University Press, 1991.

Markell, E. K., M. Voge, and D. T. John. Medical Parasitology. 7th ed. Philadelphia: Saunders, 1992.

Phillips, R. S. Malaria. Institute of Biology's Studies in Biology, No. 152. London: E. Arnold, 1983.

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Malaria

Malaria

Definition

Malaria is a serious, infectious disease spread by certain mosquitoes. It is most common in tropical climates. It is characterized by recurrent symptoms of chills, fever, and an enlarged spleen. The disease can be treated with medication, but it often recurs. Malaria is endemic (occurs frequently in a particular locality) in many third world countries. Isolated, small outbreaks sometimes occur within the boundaries of the United States.

Description

Malaria is not a serious problem in the United States. Within the last decade, only about 1,200 cases have been reported each year in this country, mostly by people who were infected elsewhere. Locally transmitted malaria has occurred in California, Florida, Texas, Michigan, New Jersey, and New York City. While malaria can be transmitted in blood, the American blood supply is not screened for malaria. Widespread malarial epidemics are far less likely to occur in the United States, but small, localized epidemics could return to the western world.

The picture is far more bleak outside the territorial boundaries of the United States. A recent government panel warned that disaster looms over Africa from the disease. Malaria infects between 300 and 500 million people every year in Africa, India, southeast Asia, the Middle East, Oceania, and Central and South America. About 2 million of the infected die each year. Most of the cases and almost all of the deaths occur in sub-Saharan Africa. At the present time, malaria kills about twice as many people each year as does AIDS. As many as half a billion people worldwide are left with chronic anemia due to malaria infection. In some parts of Africa, people battle up to 40 or more separate episodes of malaria in their life-times. The spread of malaria is becoming even more serious as the parasites that cause malaria develop resistance to the drugs used to treat the condition.

Causes and symptoms

Human malaria is caused by four different species of a parasite called plasmodium: Plasmodium falciparum (the most deadly), P. vivax, P. malariae, and P. ovale. The last two are fairly uncommon. Many animals can get malaria but human malaria does not spread to animals. In turn, animal malaria does not spread to humans.

A person gets malaria when bitten by a female mosquito who is looking for a blood meal and is infected with the malaria parasite. The parasites enter the blood stream and travel to the liver, where they multiply. When they re-emerge into the blood, symptoms appear. By the time a person shows symptoms, the parasites have reproduced very rapidly, clogging blood vessels and rupturing blood cells.

Malaria cannot be casually transmitted directly from one person to another. Instead, a mosquito bites an infected person and then passes the infection on to the next human it bites. It is also possible to spread malaria via contaminated needles or in blood transfusions. This is why all blood donors are carefully screened with questionnaires for possible exposure to malaria.

The amount of time between the mosquito bite and the appearance of symptoms varies, depending on the strain of parasite involved. The incubation period is usually between 8 and 12 days for falciparum malaria, but it can be as long as a month for the other types. Symptoms from some strains of P. vivax may not appear until eight to 10 months after the mosquito bite occurred.

The primary symptom of all types of malaria is the "malaria ague" (chills and fever). In most cases, the fever has three stages, beginning with uncontrollable shivering for an hour or two, followed by a rapid spike in temperature (as high as 106 °F, or 41.1 °C), which lasts for three to six hours. Then, just as suddenly, the affected person begins to sweat profusely, which will quickly bring down the fever. Other symptoms may include fatigue, severe headache, or nausea and vomiting. As the sweating subsides, an individual typically feels exhausted and falls asleep. In many cases, this cycle of chills, fever, and sweating occurs every other day, or every third day, and may last for between a week and a month. Those with the chronic form of malaria may have a relapse as long as 50 years after the initial infection.

Falciparum malaria is far more severe than other types of malaria because the parasite attacks all red blood cells, not just the young or old cells, as do other types. It causes the red blood cells to become very "sticky." A person with this type of malaria can die within hours of the first symptoms. The fever is prolonged. So many red blood cells are destroyed that they block the blood vessels in vital organs (especially the kidneys ), and the spleen becomes enlarged. There may be brain damage, leading to coma and convulsions. The kidneys and liver may fail.

Malaria in pregnancy can lead to premature delivery, miscarriage, or stillbirth.

Certain kinds of mosquitoes (called anopheles) can pick up the parasite by biting an infected human. (The more common kinds of mosquitoes in the United States do not transmit the infection.) This is true for as long as that human has parasites in the blood. Since strains of malaria do not protect against each other, it is possible to be re-infected with the parasites again and again. It is also possible to develop a chronic infection without developing an effective immune response.

Diagnosis

Malaria is diagnosed by examining blood under a microscope. The parasite can be seen in the blood smears on a slide. These blood smears may need to be repeated over a 72-hour period to make an accurate diagnosis. Antibody tests are not usually helpful because many people developed antibodies from past infections, and the tests may not be readily available.

Anyone who becomes ill with chills and fever after being in an area where malaria exists must see a doctor and mention the recent travel to endemic areas. A person with the above symptoms who has been in a high-risk area should insist on a blood test for malaria. The doctor may believe the symptoms are just the common flu virus. Malaria is often misdiagnosed by North American doctors who are not used to seeing the disease. Delaying treatment of falciparum malaria can be fatal.

Treatment

Falciparum malaria is a medical emergency that must be treated in a hospital. The type of drugs, the method of giving them, and the length of the treatment depend on where the malaria was contracted and how sick is the affected person.

For all strains except falciparum, the treatment for malaria is usually chloroquine (Aralen) by mouth for three days. Those falciparum strains suspected to be resistant to chloroquine are usually treated with a combination of quinine and tetracycline. In countries where quinine resistance is developing, other treatments may include clindamycin (Cleocin), mefloquin (Lariam), or sulfadoxone/pyrimethamine (Fansidar). Most persons receive an antibiotic for seven days. Those who are very ill may need intensive care and intravenous (IV) malaria treatment for the first three days.

Anyone who acquired falciparum malaria in the Dominican Republic, Haiti, Central America west of the Panama Canal, the Middle East, or Egypt can still be cured with chloroquine. Almost all strains of falciparum malaria in Africa, South Africa, India, and southeast Asia are now resistant to chloroquine. In Thailand and Cambodia, there are strains of falciparum malaria that have some resistance to almost all known drugs.

A person with falciparum malaria needs to be hospitalized and given antimalarial drugs in different combinations and doses depending on the resistance of the strain. The individual may need IV fluids, red blood cell transfusions, kidney dialysis, and assistance breathing.

A drug called primaquine may prevent relapses after recovery from P. vivax or P. ovale. These relapses are caused by a form of the parasite that remains in the liver and can reactivate months or years later.

Another new drug, halofantrine, is available abroad. While it is licensed in the United States, it is not marketed in this country and it is not recommended by the Centers for Disease Control and Prevention in Atlanta, Georgia.

Preventing mosquito bites while in the tropics is an important way to avoid malaria.

Alternative treatment

The Chinese herb qiinghaosu (the western name is artemisinin) has been used in China and southeast Asia to fight severe malaria, and became available in Europe in 1994. Because this treatment often fails, it is usually combined with another antimalarial drug (mefloquine) to boost its effectiveness. It is not available in the United States and other parts of the developed world due to fears of its toxicity, in addition to licensing and other issues.

A western herb called wormwood (Artemesia annua) that is taken as a daily dose can be effective against malaria. Protecting the liver with herbs like goldenseal (Hydrastis canadensis), Chinese goldenthread (Coptis chinensis), and milk thistle (Silybum marianum) can be used as preventive treatment.

Prognosis

If treated in the early stages, malaria can be cured. Those who live in areas where malaria is epidemic, however, can contract the disease repeatedly, never fully recovering between bouts of acute infection.

Health care team roles

Physicians, assisted by laboratory technicians, usually make a diagnosis of malaria. Nurses may provide prevention education and support during recovery from malaria ague.

Prevention

Several researchers are currently working on a malarial vaccine, but the complex life cycle of the malaria parasite makes it difficult. A parasite has much more genetic material than a virus or bacterium. For this reason, a successful vaccine has not yet been developed.

Malaria is an especially difficult disease to vaccinate against because the parasite goes through several separate stages. One recent, promising vaccine appears to have protected up to 60% of people exposed to malaria. This was evident during field trials for the drug that were conducted in South America and Africa. It is not yet commercially available.

The World Health Association (WHO) has been trying to eliminate malaria for the past 30 years by controlling mosquitoes. Their efforts were successful as long as the pesticide DDT killed mosquitoes and antimalarial drugs cured those who were infected. Today, however, the problem has returned a hundred-fold, especially in Africa. Because both the mosquito and parasite are now extremely resistant to the insecticides designed to kill them, governments are now trying to teach people to take antimalarial drugs as a preventive medicine and avoid being bitten by mosquitoes.

Travelers to high-risk areas should use insect repellent containing DEET for exposed skin. Because DEET is toxic in large amounts, children should not use a concentration higher than 35%. DEET should not be inhaled. It should not be rubbed onto the eye area, on any broken or irritated skin, or on children's hands. It should be thoroughly washed off after coming indoors.

Individuals who use the following preventive measures get fewer infections than those who do not:

  • Between dusk and dawn, remain indoors in well-screened areas.
  • Sleep inside pyrethrin or permethrin repellent-soaked mosquito nets.
  • Wear clothes over the entire body.

Anyone visiting endemic areas should take antimalarial drugs starting a day or two before leaving the United States. The drugs used are usually chloroquine or mefloquine. This treatment is continued through at least four weeks after leaving the endemic area. However, even those who take antimalarial drugs and are careful to avoid mosquito bites can still contract malaria.

International travelers are at risk for becoming infected. Most Americans who have acquired falciparum malaria were visiting sub-Saharan Africa. Travelers in Asia and South America are less at risk. Travelers who stay in air conditioned hotels on tourist itineraries in urban or resort areas are at lower risk than backpackers, missionaries, and Peace Corps volunteers. Some people in western cities where malaria does not usually exist may acquire the infection from a mosquito carried onto a jet. This is called airport or runway malaria.

KEY TERMS

Arteminisinins— An antimalarial family of products derived from an ancient Chinese herbal remedy. Two of the most popular varieties are artemether and artesunate, used mainly in southeast Asia in combination with mefloquine.

Chloroquine— This antimalarial drug was first used in the 1940s, until the first evidence of quinine resistance appeared in the 1960s. It is now ineffective against falciparum malaria almost everywhere. However, because it is inexpensive, it is still the antimalarial drug most widely used in Africa. Native individuals with partial immunity may have better results with chloroquine than a traveler with no previous exposure.

Mefloquine— An antimalarial drug that was developed by the United States Army in the early 1980s. Today, malaria resistance to this drug has become a problem in some parts of Asia (especially Thailand and Cambodia).

Quinine— One of the first treatments for malaria, quinine is a natural product made from the bark of the Cinchona tree. It was popular until being superseded by the development of chloroquine in the 1940s. In the wake of widespread chloroquine resistance, however, it has become popular again. It or its close relative quinidine can be given intravenously to treat severe falciparum malaria.

Sulfadoxone/pyrimethamine (Fansidar)— This antimalarial drug developed in the 1960s is the first drug tried in some parts of the world where chloroquine resistance is widespread. It has been associated with severe allergic reactions due to its sulfa component.

Resources

BOOKS

Humphreys, Margaret. Malaria in the United States: Poverty, Race, and Public Health. Baltimore: Johns Hopkins University Press, 2001.

Krause, Peter J. "Malaria." In Nelson Textbook of Pediatrics, 16th ed., edited by Richard E. Behrman, et al. Philadelphia: Saunders, 2000, 1049-1052.

Krogstad, Donald J. "Malaria." In Cecil Textbook of Medicine, 21st ed., edited by Goldman, Lee and Bennett, J. Claude. Philadelphia: W.B. Saunders, 2000, 1947-1951.

Poser, Charles M. and Bruyn, G.W. An Illustrated History of Malaria. New York: Parthenon Publishing Group, 1999.

White, Nicholas J and Bremen, Joel G. "Malaria and Other Diseases Caused by Red Blood Cell Parasites." In Harrison's Principles of Internal Medicine, 14th ed., edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, 1180-1189.

PERIODICALS

Albrecht, H., Lennox, J., del Rio, C. "Quinidine and malaria." Archives of Internal Medicine 161, no. 8 (2001): 1118-1119.

Arya, S.C. "Limitations of rapid tests for malaria diagnosis by travelers." Journal of Travel Medicine 7, no. 6 (2000): 340-342.

Etchegorry, M. G., Matthys, F., Galinski, M., White, N. J., Nosten, F. "Malaria epidemic in Burundi." Lancet 357, no. 9261 (2001): 1046-1047.

Kerr, C. "Malaria vaccine news." Trends in Microbiology 9, no. 5 (2001): 202-207.

Lawler, S. "Boost for development of malaria vaccine." Trends in Cellular Biology 11, no. 4 (2001): 151-157.

Marshall, H. "Vaccine prevents malaria parasite from infecting mosquitoes." Trends in Immunology 22, no. 3 (2001): 125-132.

Smith, T. A., Leuenberger, R., Lengeler, C. "Child mortality and malaria transmission intensity in Africa." Trends in Parasitology 17, no. 3 (2001): 145-149.

Taverne, J. "Malaria, HIV and mosquito control on the Web." Trends in Parasitology 17, no. 3 (2001): 155-156.

Taylor-Robinson, A. "Immunity to malaria increases during puberty." Trends in Parasitology 17, no. 5 (2001): 213-215.

Taylor-Robinson, A. "Rationale for malaria anti-toxin therapy." Trends in Parasitology 17, no. 3 (2001): 119-124.

ORGANIZATIONS

Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333. (404) 639-3534 or (800) 311-3435. 〈http://www.cdc.gov/nchstp/tb/faqs/qa.htm〉. 〈http://www.cdc.gov/netinfo.htm〉.

Pan American Health Organization, 525 Twenty-third Street, NW, Washington, D.C. 20037. (202) 974-3000. Fax: (202) 974-3663. 〈http://www.paho.org/〉. [email protected]

World Health Organization, Communicable Diseases, 20 Avenue Appia, 1211 Geneva 27, Switzerland. +41 (22) 791 4140. Fax: +41 (22) 791 4268. 〈http://www.who.int/gtb〉. [email protected]

OTHER

Centers for Disease Control and Prevention. 〈http://www.cdc.gov/travel/malinfo.htm〉 and 〈http://www.cdc.gov/ncidod/dpd/parasites/malaria/default.htm〉.

Malaria Foundation International. 〈http://www.malaria.org/〉.

Malaria Vaccine Initiative. 〈http://www.malariavaccine.org/〉.

Medical Research Programme of South Africa. 〈http://www.malaria.org.za/〉.

National Institutes of Health. 〈http://mim.nih.gov/〉.

World Health Organization Malaria Fact Sheets. 〈http://www.who.int/health-topics/malaria.htm〉 and 〈http://www.who.int/inf-fs/en/fact094.html.〉.

World Health Organization Tropical Disease Research. 〈http://www.wehi.edu.au/MalDB-www/who.html〉.

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Malaria

Malaria

Life cycle

Symptoms

Treatment and control

Resources

Malaria has been described as the worlds greatest public health concern. It is caused by one of several strains of the Plasmodium protozoan, a one-celled parasite that is transmitted by the bite of the Anopheles mosquito. Up to 500 million people are infected with malaria each year, resulting in 13 million deaths annually, primarily in children under five-years-old in sub-Saharan Africa, Asia, and South America, where over 90% of malaria deaths occur. Malaria has essentially been eradicated in most parts of North America, Europe, and Russia, although infected travelers and immigrants can reintroduce the disease if bitten by an infected mosquito. Malaria is on the increase worldwide and presents a major burden for tropical communities and travelers, particularly in areas where the parasite has evolved resistance to the drugs used to treat it.

Life cycle

Alphonse Laveran, a French Army physician working in North Africa in the 1880s, was the first to observe malarial parasites in human blood. Their mode of transmission was not understood, however, until Ronald Ross, a British medical officer in India, found the organisms within the bodies of Anopheles mosquitoes. Malaria is caused by four species of parasitic protozoa: Plasmodium vivax, P. ovale, P. malariae, and P. falciparum. These organisms have complex life cycles involving several different developmental stages in both human and mosquito hosts. Present as infective sporozoites in the salivary glands of the mosquito, they are transferred by the mosquitos bite to the human blood stream, where they travel to the liver. There, each sporozoite divides into thousands of merozoites, which emerge into the blood once again and begin invading the hosts red blood cells. This event triggers the onset of disease symptoms, as the merozoites consume proteins necessary for proper red blood cell function, including hemoglobin. The merozoites mature into the trophozoite phase and reproduce by division. As a result, many more merozoites are released into the blood when the host cell finally ruptures. In P. vivax and P. ovale infection, some sporozoites may delay their development in the liver, lingering in a dormant phase, but emerging later and causing the characteristic recurrence of symptoms.

The cycle of red blood cell invasion and parasite multiplication repeats itself many times during a bout of malaria. If a mosquito bites the affected person, the insect takes up merozoites, which reproduce sexually within its gut. The cycle completes itself as the larval parasites pass through the gut wall and make their way to the mosquitos salivary glands, from whence they may again be transferred to a human host as sporozoites.

Symptoms

Malaria is easily misdiagnosed because it resembles many other diseases. Early symptoms include malaise, fatigue, headache, nausea and vomiting, and muscular aches; after several hours, the characteristic high fever and chills occur. The bodys principal defenses are fever and filtration of infected red blood cells in the spleen. Neither of these mechanisms, however, is completely effective in ridding the body of the parasite.

P. falciparum is the most dangerous of the four malaria strains, and can kill a healthy adult in 48 hours. This type is so dangerous because the parasitized red blood cells can become sequestered in the deep vascular beds of the brainhence the term cerebral malaria for severe malaria infection with this strain. Sequestration happens because parasite-derived proteins on the surface of infected red blood cells cause them to stick to each other and to the cells lining the hosts venules and capillaries (two types of small blood vessel), especially in the brain and heart. This has the effect of keeping the parasite away from the hosts natural defense system. It also means that the progress of the disease can be hidden from a health practitioner who draws blood from a peripheral body region (for example, the arm); such blood will not reveal the true extent of the infection. Delirium, convulsions, and coma are features of falciparum malaria, which is associated with a 20% mortality rate in adults.

Treatment and control

A connection between swampy areas and fever was made centuries ago, and the word malaria reflects the popular belief that the illness was caused by bad air (Italian, mal aria ). During the sixteenth century, people discovered that the disease could be treated using quinine, a compound derived from the bark of the tropical Cinchona tree. No vaccine for malaria has yet been developed, although the U.S. Army has worked to develop one for decades. In the summer of 2006, Army researchers began clinical trials of the thirtieth potential vaccine since the Army began to tackle the disease. Currently, the synthetic agent chloroquine is the most widely used antimalarial drug; it can clear nonresistant parasites from the blood in two to three days.

Malaria prophylaxis (prevention) is prescribed according to type of malaria parasite present in the desired destination. Doxycicline is often prescribed for malaria prophylaxis. Chloroquine is sometimes combined with the drug primaquine for protection for people who are at particular risk of becoming infected while visiting in malarial regions. Chloroquine, an older antimalarial drug, has shown some renewed effectiveness in some malarial areas. Chloroquine attacks parasites that are circulating in the blood; primaquine is necessary to eradicate dormant parasites from the liver. Malaria prophylaxis begins one week before entering a malarial area and continues for several weeks after returning to unaffected areas, because of the complex nature of the parasites life cycle and the potential for relapse. Other drugs used for preventing malaria include atovaquone/proguanil and mefloquine.

Unfortunately, many people experience side effects from antimalarial medications. Further, chloroquine-resistant strains of falciparum malaria are on the increase worldwide. For this resistant parasite, the drug mefloquine is the preferred method of prophylaxis and treatment, although resistance to this drug may emerge rapidly, and resistant strains have been found in areas where the drug has never been used.

Environmental efforts at preventing the disease have been directed at draining swampy areas and spraying for mosquitoes in areas where they breed. An insecticide spraying campaign undertaken in India was effective for several years, until the mosquitoes evolved resistance to the insecticide used against them and rebounded with a vengeance. Use of the banned insecticide DDT is problematic as it has numerous environmental side effects, but is being considered for use again in areas where mosquitoes carrying resistant malaria are present.

Avoiding being bitten may be the best defense, and people in malarial areas are advised to avoid the outdoors during peak mosquito feeding times (dusk and dawn), to use window screens, and to sleep under nets treated with insecticide. However, there are millions of people in malaria-infested regions who are too poor to acquire window screens or netting.

In areas where malaria is endemic (ever-present), many individuals appear to be immune to the disease. In some populations, including those of India, Latin America, southern Europe, and especially Africa, the gene causing sickle-cell anemia is present. This gene is directly connected with malaria immunity: a person possessing one copy of the sickle-cell gene will be malaria-resistant, while a person possessing two copies of the gene will be both malaria-resistant and sickle-cell anemic. Further, even among people who do not have the sickle-cell gene at all, not all infected individuals have symptoms; many individuals will host parasites within their bodies for months and years without showing symptoms. This suggests that a vaccine could be developed, if the mechanism of host immunity could be identified. Thus far, however, the complexity of the immune response and the diversity of the parasites evasive mechanisms have prevented researchers from clinically assessing immunity. Evidently, each of the protozoans developmental stages bears different antigens (the molecules that trigger the development of immunity in the host). What is more, these factors are different for each of the four strains of the parasite. This explains why no individual is known to be immune to all four malarial strains.

KEY TERMS

Antigen A molecule, usually a protein, that the body identifies as foreign and toward which it directs an immune response.

Merozoite The motile, infective stage of malaria, responsible for disease symptoms.

Parasite An organism that lives on or within a host organism to the detriment of the host.

Protozoan Microscopic, single-celled, eukaryotic organism, classified in the kingdom Protista.

Sporozoite Developmental stage of the malaria protozoan during which it is transferred from mosquito to human host.

Trophozoite The amoeboid, vegetative stage of the malaria protozoa.

The fact that Europe and North America have not been afflicted by malaria since the early twentieth century has meant that for decades, relatively little research was done on malaria vaccines, new malarial drugs, or specialized insecticides. Of the 1,223 new drugs developed from 1975 to 1996, only three were antimalarials. However, first world funding for malaria research has increased dramatically since the mid-1990s, and in 2002, researchers announced that they had completely characterized the genomes of the Plasmodium falciparum parasite and its vector (means of transmission), the Anopheles gambiae mosquito. It is hoped that this knowledge will increase understanding of parasite-host and parasite-vector relationships, symptom causation, and drug responses, and will accelerate vaccine development and suggest possibilities for new drugs. For instance, researchers may design drugs targeted to blocking the function specific genes essential to the survival of the parasite. In addition, philanthropic organizations such as the Bill and Melinda Gates Foundation have made conquering malaria among their top priorities.

See also Tropical diseases.

Resources

BOOKS

Day, Nancy. Malaria, West Nile, and Other Mosquito-Borne Diseases. Berkeley Heights, NJ: Enslow Publishers, 2001.

Giles, Herbert M., and David Warrell, eds. Essential Malariology, 4th ed. London: Edward Arnold, 2002.

Honigsbaum, Mark. The Fever Trail. New York: Farrar Straus & Giroux, 2002.

Spielman, Andrew, and Michael DAntonio. Mosquito: A Natural History of Our Most Persistent and Deadly Foe. New York: Hyperion, 2001.

PERIODICALS

Greenwood, Brian, and Theonest Mutabingwa. Malaria in 2002. Nature. 415 (February 7, 2002): 670672.

OTHER

Centers for Disease Control, National Center for Infectious Diseases, Travelers Health. Malaria (July 10, 2001) <http://www.cdc.gov/travel/malinfo.htm> (January 17, 2003).

Susan Andrew

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Malaria

Malaria

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

Primary Source Connection

Primary Source Connection

BIBLIOGRAPHY

Introduction

Malaria is the leading cause of death worldwide from parasitic infection. According to the World Health Organization (WHO) there are more than 500 million cases of malaria each year in tropical and subtropical regions of the world, and one to two million deaths, most of which occur in sub-Saharan Africa, with children being disproportionately affected.

The name “malaria” means “bad air” which used to be thought the cause of the disease. However, in the nineteenth century, it was established that malaria is caused by Plasmodia which are single-celled parasites that are carried by mosquitoes belonging to the Anopheles genus. Four species of Plasmodia are involved in malaria: P. falciparum, P. vivax, P. ovale and P. malariae. Malaria caused by P. falciparum is by far the most serious and the cause of most fatalities. There are several drugs that can be used for both the treatment and prevention of malaria. However, parasites have evolved resistance to one of the main ones, chloroquine, in certain areas.

Disease History, Characteristics, and Transmission

What historical accounts of war call “marsh fever,” “intermittent fever,” or “remittent fever,” match current descriptions of malaria. One of the earliest recorded casualties of malaria may have been the great military campaigner of ancient Greece, Alexander the Great, who died of a fever in 323 BC. Malaria and dysentery also caused much sickness during the Crusades (1095–c.1300). It was also a major cause of disease among European armies on campaigns in tropical regions up to the 1820s, when quinine—extracted from cinchona bark—was found to be useful in both treating and preventing the disease.

However, quinine proved to be only a partial solution to malaria among the military, for it continued to be a problem during World War I (1914–1918) in Macedonia, Mesopotamia, and East Africa. In 1918, around 90% of British and French troops in Macedonia contracted malaria despite the use of quinine. In the World War II (1939–1945), quinine supplies were limited, and military commanders had lost their faith in it, so the Allies turned to the synthetic drug mepacrine instead. This was shown to have a dramatic effect in reducing the rate of malaria among Australian troops in New Guinea and among Allied troops in Burma. The insecticide DDT was introduced in 1944 and this was sprayed from the air to protect troops operating in marshy malarious areas of Burma and Italy.

The malaria parasite enters the body through the bite of an infected female Anopheles mosquito and travels through the blood to the liver, then back to the blood, undergoing a complex life cycle as it does so. The incubation time of malaria is typically between seven and 30 days. Symptoms occur within a month in 75% of cases, and within two months in 90% of cases. For travelers returning from areas where malaria is endemic, symptoms may, therefore, not start until well after their return home. Sometimes persons are infected with two or more species of Plasmodium.

The specific pattern of symptoms experienced in a bout of malaria depends upon which of the four species of Plasmodium is responsible for the disease. High fever with chills, headache, aching limbs, nausea, and diarrhea are common symptoms, however. Often the patient will experience a cycle of shivering and chills followed by flushing, fever, and profuse sweating. This bout of symptoms tends to spike (peak or temporarily worsen) every day or so, and is related to the parasites bursting out of the red blood cells they have infected.

In acute malaria, there may be swollen liver, pallor (paleness), jaundice (yellowing of the skin and eyes), anemia (reduced ability of blood to transport oxygen), and respiratory distress. Complications are most common among children, pregnant women and travelers and are usually caused by P. falciparum malaria. Cerebral malaria is the most serious complication of malaria and accounts for 80% of all fatalities from the disease. Around 0.5–1% of P. falciparum malaria cases lead to cerebral malaria. The other Plasmodium species do not cause cerebral malaria. The symptoms of cerebral malaria include seizures, stupor and coma. The death rate is between 20 and 50%. However, a full recovery without morbidity (disease or disability) is common among many survivors.

Other complications of P. falciparum malaria include a swollen spleen, kidney failure, and low blood sugar—the latter occurring because the parasites consume glucose 75 times faster than the red blood cell and therefore deplete its supplies. Death from a ruptured spleen has been reported in P. ovale malaria.

The risk of relapse depends upon the type of malaria the patient has. P. falciparum malaria, although responsible for most fatalities, does not actually lead to longterm relapse although survivors may suffer flare-ups over the year after the first attack. P. vivax causes a relapsing form of the disease, lasting up to five years, because of dormant parasites residing in the liver, as does P. ovale, although the latter is far less common. P. malariae may produce a low-grade chronic infection characterized by bouts of fever, lasting up to 50 years, although it too is uncommon.

The process by which Plasmodia parasites are transmitted begins with the bite of the infected female Anopheles mosquito, in order to take a blood meal from the host. The infectious sporozoite form of the parasite is injected into the skin through the mosquito's salivary glands, and travels through the bloodstream to the liver. They then reproduce asexually within liver cells. This process takes one to two weeks, and during this period, the patient will not have any symptoms.

The infected liver cells rupture, releasing parasite forms called merozoites which enter red blood cells, maturing and multiplying. This process takes about 48 hours and then these parasites rupture the red blood cell, releasing more merozoites, which go on to infect further red blood cells. The release of the merozoites causes inflammation and a release of toxins, which causes a spike of fever. This stage can cause a massive increase in the number of parasites, particularly in P. falciparum because this species infects all types of red blood cells. It is possible for more than 1% of all the red blood cells in the body to contain P. falciparum parasites.

In a further twist to this complex life cycle, some Plasmodium merozoites develop within the red blood cells into sexual forms, known as gametocytes. If another mosquito bites, she may take up these parasites in the blood meal and they can mate sexually inside the mosquito to form more sporozoites, ready to complete the cycle from the beginning with the next bite of the same, or another, host.

P. vivax and P. ovale have a hepatic form which lies dormant for several weeks, giving rise to relapse symptoms when they are released into the blood. P. malariae may be transmitted from person-to-person through blood and organ donations from people who are already infected with the parasite, even though they may not have symptoms. Each stage in the life cycle of each species of Plasmodium has a specific morphology, which allows for accurate diagnosis in expert hands.

Scope and Distribution

There are around 500 million symptomatic cases of malaria every year around the world. Most of the one to two million deaths occur in Africa and at least half of these occur among children. In the United Kingdom and the United States, there are 1,000 to 2,000 cases of malaria each year, and around ten deaths, mainly occurring in travelers returning from endemic areas, leading to around ten deaths. Around 80% of those affected have returned from traveling in Africa.

Malaria is endemic in tropical and subtropical regions, including sub-Saharan Africa, South East Asia, Papua New Guinea, the Pacific States, Haiti and parts of South America. The parasites require a temperature of at least 68°F (20°C) to complete their lifecycles. Besides temperature, humidity and rainfall are factors affecting the transmission of malaria. The disease is endemic in more than 100 countries and territories, with more than 40% of the world's population being at risk.

Malaria has been known for more than 4,000 years and the disease used to be even more widespread than it is today, for endemic malaria has been eliminated from the United States, Europe, Puerto Rico, Chile, Israel, Lebanon, Taiwan, Singapore, most of the Caribbean, and North Korea. Some Pacific islands do not have malaria, despite favorable climatic factors, because Anopheles mosquitoes do not live there. However, despite elimination from some countries, there has been a resurgence in others, such as Sri Lanka.

The four Plasmodium parasites have differing geographical distributions. P. falciparum has the widest spread, and is found in Central and South America, Haiti, the Dominican Republic, sub-Saharan Africa, India, Pakistan and South East Asia. P. vivax occurs in sub-Saharan Africa, Central and South America and Asia. P. ovale occurs in sub-Saharan Africa, South East Asia and Papua New Guinea. P. malariae is found only in sub-Saharan Africa. There are 430 species in the Anopheles genus and only 30 to 50 transmit malaria. Some prefer to bite non-human animals, other are active inside rather than outside—therefore, risk of contracting malaria depends very much on the nature of the local mosquito population.

Returning travelers are especially at risk of malaria, as are pregnant women. Malaria should always be suspected if someone develops fevers and chills up to one year after return from a malarious area. Malaria in a pregnant woman can cause fetal death or low birth weight. The disease can also be passed on during childbirth, and will cause severe anemia in the newborn.

Malaria has often accompanied military campaigns throughout the course of human history because the disease is encouraged by the conditions of war. The movement of troops or refugees leads to the spread of many kinds of parasites, including Plasmodia, and those without immunity are at risk when they travel to areas where the disease is endemic. Moreover, war may damage drainage and irrigation systems, which encourages the breeding of mosquitoes.

Treatment and Prevention

There are several drugs which can be used for the treatment and prevention of malaria. These include chloroquine, mefloquine, pyrimethamine, proguanil, primaquine, and artemisinin. The latter is the most recent drug introduced and it comes from the Chinese herbal remedy qinghaosu. Drug resistance has begun to emerge in some areas, with chloroquine resistant P. falciparum being a problem in Africa and elsewhere, and chloroquine resistant P. vivax in South East Asia. The WHO recommends the use of arte-mesinin in combination with another anti-malarial drug as first-line treatment for malaria, but the choice depends upon the Plasmodium species involved and the extent of drug resistance in the area where the disease was contracted.

Patients with malaria need close medical attention as well as medication. Often this means supervision in the high dependency or intensive care unit. It is especially important that fluid balance and glucose levels are maintained.

Prevention of malaria involves taking prophylactic medication before, during and after travel to malarious areas. The highest risk is a trip to an area where there is chloroquine-resistant P. falciparum where mefloquine, doxycycline or Malarone (a combination of atovaquone-proguanil) is often prescribed for malaria prophylaxis (prevention). Would-be travelers should take advice from the Centers for Disease Control and Prevention (CDC) or their national equivalent on the specific protection they need. Pregnant women, in particular, need prophylaxis. Only chloroquine and proguanil are recommended for use during pregnancy, therefore travel to chloroquine-resistant areas should be avoided.

The other key to prevention is avoiding the bite of the Anopheles mosquito. This can be challenging, as it is smaller and less conspicuous than some other mosquito species, and a bite could go unnoticed. Anopheles bite primarily between dusk and dawn. Wearing clothes of thick woven material, like cotton, that cover most of the body and sleeping under bed nets impregnated with permethrin insecticide are helpful, along with the use of an insect repellent containing DEET (diethylmethylto-luamide) on exposed areas of skin. Malaria sometimes occurs despite preventive measures, including medication, so those who at risk should still be on the lookout for telltale symptoms like fever.

Impacts and Issues

An effective vaccine would be an enormous advance in the global fight against malaria. For 20 years, various agencies of the United Nations, the World Bank and other non-governmental organizations have been searching for a vaccine as a top priority in their tropical disease research programs. Success has, unfortunately, proved elusive. It is hard to grow the malaria parasites in culture, which means the experiments that would help develop a vaccine cannot readily be carried out. The complex lifecycle of the parasites, which are constantly evolving, is also a huge challenge to vaccine researchers. Some people in endemic areas seem to have a natural immunity to malaria. Understanding the biochemical basis of this might open up a route to a vaccine but, so far, this has proved difficult.

Each death from malaria is a tragedy—whether it occurs in a returning traveler to the United States or in a child in Africa. There have been many needless deaths because of wrong or delayed diagnosis. Many doctors in the West are unfamiliar with malaria and may not realize that gastrointestinal symptoms are often prominent in the disease; fever may not be the only symptom. Returning travelers may assume that if they have taken prophylactic medication, then protection is assured. Symptoms setting in several weeks or even months after return from a malarious area may wrongly be assumed to be severe influenza.

The correct diagnosis of malaria depends upon identifying the parasites in a blood smear treated with Giemsa stain. Both thin and thick smears are usually examined. The thin smear preserves the morphology of the parasites so that the species involved can be identified. The thick smear contains more parasites and allows for more rapid diagnosis. Levels of parasites in the blood fall between bouts of fever and the smear may appear negative, even if the person has the disease. Three negative smears, taken at intervals, are required to definitely exclude the disease.

Malaria continues to be a global health problem. The disease has re-emerged in places where it was assumed the disease has been eradicated. For instance, Sri Lanka and India were virtually free of malaria at the end of the 1970s, but from the 1980s, the number of cases began to increase, reaching levels not seen since before World War II by the 1990s. Resistance of the parasites to anti-malarial drugs, and resistance of Anopheles mosquitoes to insecticides are the major factors in the resurgence of the disease. Moreover, increased movements by travelers and migrants on a global scale are likely to add to the risk of re-introducing the malaria to countries where it had previously been eradicated.

WORDS TO KNOW

ENDEMIC: Present in a particular area or among a particular group of people.

GAMETOCYTE: A germ cell with the ability to divide for the purpose of producing gametes, either male gametes called spermatocytes or female ones called oocytes.

MEROZOITE: The motile, infective stage of malaria, responsible for disease symptoms.

MORBIDITY: The term “morbidity” comes from the Latin word “morbus,” which means sick. In medicine it refers not just to the state of being ill, but also to the severity of the illness. A serious disease is said to have a high morbidity.

PARASITE: An organism that lives in or on a host organism and that gets its nourishment from that host. The parasite usually gains all the benefits of this relationship, while the host may suffer from various diseases and discomforts, or show no signs of the infection. The life cycle of a typical parasite usually includes several developmental stages and morphological changes as the parasite lives and moves through the environment and one or more hosts. Parasites that remain on a host's body surface to feed are called ectoparasites, while those that live inside a host's body are called endoparasites. Parasitism is a highly successful biological adaptation. There are more known parasitic species than nonparasitic ones, and parasites affect just about every form of life, including most all animals, plants, and even bacteria.

PROPHYLAXIS: Treatment to prevent the onset or recurrence of disease.

RE-EMERGENT DISEASE: A disease that has disappeared for a period of time, only to reappear at a later time.

SPOROZOITE: Developmental stage of the malaria protozoan during which it is transferred from mosquito to human host.

IN CONTEXT: CHILDREN UNDER-5 WITH FEVER WHO RECEIVED TREATMENT WITH ANY ANTIMALARIAL

The list below shows the estimated percentage of children under five years of age with fever who received treatment with any antimalarial medication as reported in February 2007 by the World Health Organization. Not all [malaria endemic] countries reported data. The year of report is indicated in parenthesis

  • Indonesia: 0.7 % (2002–03)
  • Azerbaijan: 0.8 % (2000)
  • Nicaragua: 1.8 % (2001)
  • Guyana: 2.6 % (2000)
  • Ethiopia: 3 % (2000)
  • Eritrea: 3.6 % (2002)
  • Haiti: 11.7 % (2000)
  • Rwanda: 12.6 % (2000)
  • Namibia: 14.4 % (2000)
  • Somalia: 18.5 % (1999)
  • Swaziland: 25.5 % (2000)
  • Kenya: 26.5 % (2003)
  • Burundi: 31.3 % (2000)
  • Malawi: 31.6 % (2004)
  • Mauritania: 33.4 % (2003-04)
  • Nigeria: 33.8 % (2003)
  • Senegal: 36.2 % (2000)
  • Mali: 37.6 % (2003)
  • Madagascar: 41.1 % (2004)
  • Democratic Republic of the Congo: 45.4 % (2001)
  • Timor-Leste: 47.4 % (2002)
  • Niger: 48.1 % (2000)
  • Equatorial Guinea: 48.6 % (2000)
  • Burkina Faso: 49.6 % (2003)

SOURCE: World Health Organization, World malaria report 2005. Geneva, World Health Organization and United Nations Children's Fund, 2005.

The Bill and Melinda Gates Foundation supports mosquito-borne disease research and prevention efforts worldwide, including the development of effective and affordable drugs, improvement of existing preventative measures, and vaccine development. In 2005, The Gates Foundation announced three grants totaling $258.3 million for continued research and development of anti-malarial drugs, vaccines, and insecticide-based mosquito control methods. On the eve of the first White House Malaria Summit, the Gates Foundation announced another large grant of $83.5 million to expand access to bednets and treatment in malaria prone regions.

As most scientists agree that the Earth's temperature is rising, it is likely that more areas of the world will become habitats for the Anopheles mosquito and its parasites. Therefore, the search for a vaccine and new anti-malarial drugs has never been more urgent.

Primary Source Connection

Use of the insecticide DDT in the decades after World War II helped to greatly reduce the incidence of malaria throughout many countries of the world. By the 1970s, agricultural use of DDT was linked to thinning bird eggshells, and after the populations of many birds plummeted, DDT use was banned in most developed countries by the 1985. A large drop in DDT use in developing countries followed, and by the 1990s, malaria made a resurgence.

In the following speech delivered to the National Press Club in Washington, D.C., in September 2006, Arata Kochi called for the renewed use of DDT in Africa, especially indoors in shelters made of mud and thatch, where it could function as both insect repellent and insecticide. Kochi, a Japanese physician, is the director of the malaria department for the World Health Organization. As of 2007, Kochi's plan of targeted DDT use indoors is being carried out in several sub-Saharan African nations including Zambia, South Africa, Angola, Uganda, Tanzania, and Mozambique.

WHO Malaria Head to Environmentalists: “Help Save African Babies as You Are Helping to Save the Environment.”

I am here today with one urgent message to everyone who cares about the environment. Your concern, your activism, your heroics have helped—and continue to help—protect the earth's wildlife and nature.

I am here today to ask you, please: Help save African babies as you are helping to save the environment.

African babies do not have a powerful movement like the environmental movement to champion their well-being. They need your help.

Nearly one year ago, I was asked to take charge of the World Health Organization's Global Malaria Programme. I knew the job would be a challenge. Little progress was being made in controlling malaria, even though WHO had declared—way back in 1998—that rolling back malaria would be one of its greatest priorities.

I asked my staff; I asked malaria experts around the world: “Are we using every possible weapon to fight this disease?” It became apparent that we were not. One powerful weapon against malaria was not being deployed. In a battle to save the lives of nearly one million children ever year—most of them in Africa— the world was reluctant to spray the inside of houses and huts with insecticides; especially with a highly effective insecticide known as dichlorodiphenyltrichloroethane, or “DDT.”

Even though indoor spraying with DDT and other insecticides had been remarkably effective in preventing malaria sickness and death where used, this strategy seemed to have been abandoned by most countries nearly 30 years ago. By the early 1980s, WHO was no longer actively promoting it.

Some people told me that there was a good reason why its wide scale use had been phased out. I was told the practice was unsafe for humans, birds, fish, and wildlife; that the use of DDT in the United States in the 1950s had led to the near extinction of the bald eagle. I was told that indoor spraying with DDT was “politically unpopular.”

But I believe that public health policies must be based on the science and the data, not on conventional wisdom or politics. As we examined the issue, we found that the scientific and programmatic evidence told a different story: We found that:

  • One of the best tools we have against malaria is indoor residual house spraying, as it has proven to be just as cost effective as other malaria prevention measures.
  • Of the dozen insecticides WHO has approved as safe for house spraying, the most effective is DDT.
  • DDT presents no health risk when used properly indoors. Well-managed indoor spraying programmes using DDT pose no harm to wildlife or to humans.

That is why today, after this reevaluation, the World Health Organization is announcing that indoor residual spraying with DDT and other insecticides will again play a major role in its efforts to fight the disease.

WHO is now recommending the use of indoor spraying not only in epidemic areas, but also in areas with constant and high malaria transmission, including throughout Africa.

WHO is calling on all malaria control programmes around the world to develop and issue a clear statement outlining their position on indoor spraying with long lasting insecticides such as DDT, specifying where and how it will be implemented in accordance with WHO guidelines, and how these progammes will provide all possible support to accelerate and manage this intervention effectively.

WHO will use every possible and safe method to control malaria.

Help save African babies as you are helping to save the environment. Help us advocate for careful limited use of indoor spraying. Help us set up the appropriate and proper management systems so that DDT is used effectively. And finally, help us raise the necessary funds to research and develop even more effective and affordable interventions.

Arata Kochi

KOCHI, ARATA. “WHO MALARIA HEAD TO ENVIRONMENTALISTS: HELP SAVE AFRICAN BABIES AS YOU ARE HELPING TO SAVE THE

ENVIRONMENT.” WORLD HEALTH ORGANIZATION PRESS

STATEMENT. SEPTEMBER 15, 2006.

Primary Source Connection

Malaria is an ancient killer. For thousands of years, no one knew exactly what caused malaria and, therefore, no one could stop it. In 1880, Charles-Louis-Alphonse Laveran, a French military physician serving in Algeria, identified the plasmodium parasite in the blood of a sick artilleryman. Seventeen years later in India, Captain Ronald Ross extracted a plasmodium cyst from a dissected female Anopheles mosquito and identified malaria as an insect-borne parasitic disease.

Sir Ronald Ross (1857–1932) studied medicine in London before joining the Indian Medical Service in 1881. Throughout his career he focused with a single-minded intensity on the prevention of malaria, and in 1897 discovered the species of mosquito that spreads the disease. His work won him a Nobel Prize in 1902. Ross spent the remainder of his life conducting studies in the malarial centers of the world, and forming organizations to combat malaria. He directed the Ross Institute and Hospital for Tropical Diseases, established in his honor in 1926, until his death in 1932. In addition to his medical work, Ross was an acclaimed poet, and wrote the following poem shortly after discovering how malaria was transmitted.

This Day Relenting God

This day relenting God Hath placed within my hand A wondrous thing; and God Be praised. At his command,

Seeking his secret deeds With tears and toiling breath, I find thy cunning seeds, O million-murdering Death.

I know this little thing A myriad men will save, O Death, where is thy sting? Thy victory, O Grave?

Ronald Ross

ROSS, RONALD. “THIS DAY RELENTING GOD.” IN MEMOIRS WITH A FULL ACCOUNT OF THE GREAT MALARIA PROBLEM AND ITS SOLUTION LONDON: JOHN MURRAY, 1923.

See AlsoClimate Change and Infectious Disease; Travel and Infectious Disease; Tropical Infectious Diseases; Vector-borne Disease.

BIBLIOGRAPHY

Books

Lock, Stephen, John Last, and Georg Dunea. The Oxford Illustrated Companion to Medicine. Oxford: Oxford University Press, 2001.

Tan, James. Expert Guide to Infectious Diseases. Philadephia: American College of Physicians, 2002.

Wilson, Walter, and Merle A. Sande. Current Diagnosis & Treatment in Infectious Diseases. New York: McGraw Hill, 2001.

Web Sites

Centers for Disease Control and Prevention (CDC). “Malaria.” <http://www.cdc.gov/malaria> (accessed May 9, 2007).

World Health Organization. “Malaria.” May 2007 <http://www.who.int/topics/malaria/en> (accessed May 9, 2007).

Susan Aldridge

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Malaria

Malaria

Malaria has been described as the world's greatest public health problem. It is caused by one of several strains of the Plasmodium protozoan, a one-celled parasite that is transmitted by the bite of the Anopheles mosquito. Hundreds of millions of persons are struck by malaria each year, resulting in 1–3 million deaths annually, primarily in children under five-years-old in sub-Saharan Africa , where 90% of malaria deaths occur. Malaria has essentially been eradicated in North America , Europe , and Russia, although infected travelers and immigrants can reintroduce the disease if bitten by an infected mosquito. Malaria is on the increase worldwide and presents a major burden for tropical communities and travelers, particularly in areas where the parasite has evolved resistance to the drugs used to treat it.


Life cycle

Alphonse Laveran, a French Army physician working in North Africa in the 1880s, was the first to observe malarial parasites in human blood . Their mode of transmission was not understood, however, until Ronald Ross, a British medical officer in India, found the organisms within the bodies of Anophelesmosquitoes . Malaria is caused by four species of parasitic protozoa : Plasmodium vivax, P. ovale, P. malariae, and P. falciparum. These organisms have complex life cycles involving several different developmental stages in both human and mosquito hosts. Present as infective sporozoites in the salivary glands of the mosquito, they are transferred by the mosquito's bite to the human blood stream, where they travel to the liver. There, each sporozoite divides into thousands of merozoites, which emerge into the blood once again and begin invading the host's red blood cells. This event triggers the onset of disease symptoms, as the merozoites consume proteins necessary for proper red blood cell function, including hemoglobin. The merozoites mature into the trophozoite phase and reproduce by division. As a result, many more merozoites are released into the blood when the host cell finally ruptures. In P. vivax and P. ovaleinfection , some sporozoites may delay their development in the liver, lingering in a dormant phase, but emerging later and causing the characteristic recurrence of symptoms.

The cycle of red blood cell invasion and parasite multiplication repeats itself many times during a bout of malaria. If the affected person is bitten by a mosquito, the insect takes up merozoites, which reproduce sexually within its gut. The cycle completes itself as the larval parasites pass through the gut wall and make their way to the mosquito's salivary glands, from whence they may again be transferred to a human host as sporozoites.


Symptoms

Malaria is easily misdiagnosed because it resembles many other diseases. Early symptoms include malaise, fatigue, headache, nausea and vomiting, and muscular aches; after several hours, the characteristic high fever and chills occur. The body's principal defenses are fever and filtration of infected red blood cells in the spleen. Neither of these mechanisms, however, is completely effective in ridding the body of the parasite.

P. falciparum is the most dangerous of the four malaria strains, and can kill a healthy adult in 48 hours. This type is so dangerous because the parasitized red blood cells become sequestered in the deep vascular beds of the brain—hence the term "cerebral malaria" for infection with this strain. Sequestration happens because parasite-derived proteins on the surface of infected red blood cells cause them to stick to each other and to the cells lining the host's venules and capillaries (two types of small blood vessel), especially in the brain and heart . This has the effect of keeping the parasite away from the host's natural defense system. It also means that the progress of the disease can be hidden from a health practitioner who draws blood from a peripheral body region (for example, the arm); such blood will not reveal the true extent of the infection. Delirium, convulsions, and coma are features of falciparum malaria, which is associated with a 20% mortality rate in adults.

Treatment and control

A connection between swampy areas and fever was made centuries ago, and the word malaria reflects the popular belief that the illness was caused by bad air (Italian, mal aria). During the sixteenth century, people discovered that the disease could be treated using quinine , a compound derived from the bark of the tropical Cinchonatree . No vaccine for malaria has yet been developed, although preliminary trials for an initial vaccine were scheduled to begin in malaria-endemic areas in late 2003. Currently, the synthetic agent chloroquine is the most widely used antimalarial drug; it can clear nonresistant parasites from the blood in two to three days.

Chloroquine is often combined with the drug primaquine for malaria prophylaxis—that is, as protection for people who are at risk of becoming infected while visiting in malarial regions. Chloroquine attacks parasites that are circulating in the blood; primaquine is necessary to eradicate dormant parasites from the liver. Malaria prophylaxis begins one week before entering a malarial area and continues for several weeks after returning to unaffected areas, because of the complex nature of the parasite's life cycle and the potential for relapse.

Unfortunately, many persons experience extreme side effects from antimalarial medications. Further, chloroquine-resistant strains of falciparum malaria are on the increase worldwide. For this resistant parasite, the drug mefloquine is the preferred method of prophylaxis and treatment, although resistance to this drug may emerge rapidly, and resistant strains have been found in areas where the drug has never been used.

Efforts at preventing the disease have been directed at draining swampy areas and spraying for mosquitoes in areas where they breed. A DDT-spraying campaign undertaken in India was effective for several years, until the mosquitoes evolved resistance to the insecticide used against them and rebounded with a vengeance. (Further, the use of DDT is problematic as it has numerous environmental side effects; its use, though not its manufacture, is banned in the U.S.) Avoiding being bitten may be the best defense, and people in malarial areas are advised to avoid the outdoors during peak mosquito feeding times (dusk and dawn), to use window screens, and to sleep under nets treated with insecticide. However, there are millions of persons in malaria-infested regions who are too poor even to acquire window screens or netting.

In areas where malaria is endemic and ever-present, many individuals appear to be immune to the disease. In some populations, including those of India, Latin America, southern Europe, and especially Africa, the gene causing sickle-cell anemia is present. This gene is directly connected with malaria immunity: a person possessing one copy of the sickle-cell gene will be malaria-resistant, while a person possessing two copies of the gene will be both malaria-resistant and sickle-cell anemic. Further, even among persons who do not have the sickle-cell gene at all, not all infected individuals have symptoms; many individuals will host parasites within their bodies for months and years without showing symptoms. This suggests that a vaccine could be developed, if the mechanism of host immunity could be identified. Thus far, however, the complexity of the immune response and the diversity of the parasite's evasive mechanisms have prevented researchers from clinically assessing immunity. Evidently, each of the protozoan's developmental stages bears different antigens (the molecules that trigger the development of immunity in the host). What is more, these factors are different for each of the four strains of the parasite. This explains why no individual is known to be immune to all four malarial strains.

The fact that Europe and North America have not been afflicted by malaria since the early twentieth century has meant that for decades, relatively little research was done on malaria vaccines, new malarial drugs, or specialized insecticides . Of the 1,223 new drugs developed from 1975 to 1996, only three were antimalarials. However, first-world funding for malaria research has increased dramatically since the mid-1990s, and in 2002, researchers announced that they had completely characterized the genomes of the Plasmodium falciparum parasite and its vector (means of transmission), the Anopheles gambiae mosquito. It is hoped that this knowledge will increase understanding of parasite-host and parasite-vector relationships, symptom causation, and drug responses, and will accelerate vaccine development and suggest possibilities for new drugs. For instance, researchers may design drugs targeted to blocking the function specific genes essential to the survival of the parasite.

See also Tropical diseases.


Resources

books

Day, Nancy. Malaria, West Nile, and Other Mosquito-BorneDiseases. Berkeley Heights, NJ: Enslow Publishers, 2001. Honigsbaum, Mark. The Fever Trail. New York: Farrar Straus & Giroux, 2002.

Spielman, Andrew, and Michael D'Antonio Mosquito: A Natural History of Our Most Persistent and Deadly Foe. New York: Hyperion, 2001.

Giles, Herbert M., and David Warrell, eds. Essential Malariology, 4th ed. London: Edward Arnold, 2002.

periodicals

Greenwood, Brian, and Mutabingwa, Theonest. "Malaria in 2002." Nature. 415 (February 7, 2002): 670–672.

other

Centers for Disease Control, National Center for Infectious Diseases, Traveler's Health. "Malaria" July 10, 2001 [cited January 17, 2003]. <http://www.cdc.gov/travel/mal info.htm>.


Susan Andrew

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antigen

—A molecule, usually a protein, that the body identifies as foreign and toward which it directs an immune response.

Merozoite

—The motile, infective stage of malaria, responsible for disease symptoms.

Parasite

—An organism that lives on or within a host organism to the detriment of the host.

Protozoan

—Microscopic, single-celled, eukaryotic organism, classified in the kingdom Protista.

Sporozoite

—Developmental stage of the malaria protozoan during which it is transferred from mosquito to human host.

Trophozoite

—The amoeboid, vegetative stage of the malaria protozoa.

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Malaria

MALARIA

Both European and African immigrants introduced malaria, a mosquito-borne parasitical illness that produces alternating cycles of fevers and chills, to North America. From the British Isles, the early colonists brought vivax malaria, the great debilitator, that was known as "the ague." It became established in the British North American colonies, although outbreaks were only sporadic in the more northern territories, where human populations were low and adult mosquitoes died during the winter. The African captives brought falciparum malaria, the great killer. Falciparum became established in regions of the southern and middle colonies, alongside vivax malaria.

Both forms of malaria were prevalent in tidewater, marshy, riverine, and low-lying regions of the British North American colonies and are best considered as endemic. In the middle colonies, most malarial infections seem to have been vivax, with its low (characteristically, 1 to 2 percent) rate of mortality. In the southern colonies, both falciparum and vivax infections were common, particularly during the summer months.

The patterns of infection varied greatly, however, between Africans and Europeans. Almost all Africans were unable to contract vivax malaria, owing to a genetic mutation of a hemoglobin antigen known as red blood cell Duffy negativity. Europeans, on the other hand, were fully susceptible to vivax malaria, and because the vivax parasite could lie dormant in the liver, Europeans were subject to malarial relapses even without additional infection. Africans and Europeans also had differential responses to falciparum infections. Many Africans carried a genetic hemoglobin mutation known as hemoglobin S or sickle-cell that afforded considerable protection against the great killer. Europeans had no such genetic defense, and mortality during the first year of falciparum infections could run as high as 50 percent. The differential response to both vivax and falciparum underwrote European American convictions that the European and African "races" were biologically different and thus helped to rationalize the institution of racial slavery.

Malaria was, however, not only a disease of the eastern seaboard. As European American migrants opened up new territories beyond the Appalachian Mountains and began the great deforestations of the Ohio and Mississippi Valleys, malaria insinuated itself into the newly converted biomes. On soils broken by the plow, hoof, and wheel, rainfall puddled and produced ideal conditions for mosquito breeding. A frontier of malaria moved with the migrants, pushing westward a zone of endemic malarial infection.

The only effective cure during the eighteenth century was to ingest powdered bark from the cinchona tree, which grew high in the Andes. In 1820 pharmacists in France succeeded in isolating the antimalarial alkaloids from cinchona bark, and within a few years their techniques became known in the United States. In the early 1820s a new quinine industry took root in Philadelphia, and a national market developed. Quinine relieved suffering, but until the late nineteenth century the alkaloid remained expensive and its use was never sufficiently universal to break the chains of infection. Malaria continued to plague the nation into the late nineteenth century and, in some southern regions, the first half of the twentieth century.

See alsoEpidemics; Health and Disease; Medicine .

bibliography

Ackerknecht, Erwin H. Malaria in the Upper Mississippi Valley, 1760–1900. Baltimore: Johns Hopkins University Press, 1945. Reprint, New York: Arno Press, 1977.

Kiple, Kenneth F., and Virginia H. King. Another Dimension to the Black Diaspora: Diet, Disease, and Racism. New York: Cambridge University Press, 1981.

James L. A. Webb Jr.

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