Malaria

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Malaria

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

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.