Malaria Causes, Symptoms, Diagnosis, Prevention and Treatment

**trimurtulu** · 01-19-2009, 11:13 PM

Malaria : An Overview ((In-Depth Details)

Malaria is a potentially fatal tropical disease that is caused by a parasite known as Plasmodium. It is spread through the bite of an infected female mosquito.

The infected person may have feverish attacks, influenza-like symptoms, tiredness, diarrhoea or a whole range of other symptoms. Malaria should always be suspected if these symptoms occur within the first year of return from an infected area; a test should be carried out to exclude the possibility of malaria as soon as possible.

Malaria is one of the leading causes of disease and death in the world. It is estimated that there are 300-500 million new cases every year, with 1.5 to 2.7 million deaths worldwide.

Malaria occurs extensively in tropical and subtropical regions. It used to exist in the UK, but fortunately no longer. Each year 2,000 to 2,500 people return to Britain with malaria, which they have contracted abroad, and, of these, an average of 12 die. For this reason it is important to prevent malaria in those travelling to and from the tropics.

Malaria is an infectious disease caused by a parasite, Plasmodium, which infects red blood cells. Malaria is characterized by cycles of chills, fever, pain and sweating. Historical records suggest malaria has infected humans since the beginning of mankind. The name "mal 'aria" (meaning "bad air" in Italian) was first used in English in 1740 by H. Walpole when describing the disease. The term was shortened to "malaria" in the 20th century. C. Laveran in 1880 was the first to identify the parasites in human blood. In 1889, R. Ross discovered that mosquitoes transmitted malaria. Of the four species of malaria, the most serious type is Plasmodium falciparum malaria. It can be life-threatening. The other three species of malaria (P. vivax, P. malariae, and P. ovale) are generally less serious and are not life-threatening.

Life Cycle of Malaria
In nature, malaria parasites spread by infecting successively two types of hosts: humans and female Anopheles mosquitoes. In humans, the parasites grow and multiply first in the liver cells and then in the red cells of the blood. In the blood, successive broods of parasites grow inside the red cells and destroy them, releasing daughter parasites ("merozoites") that continue the cycle by invading other red cells.

The blood stage parasites are those that cause the symptoms of malaria. When certain forms of blood stage parasites ("gametocytes") are picked up by a female Anopheles mosquito during a blood meal, they start another, different cycle of growth and multiplication in the mosquito.

After 10-18 days, the parasites are found (as "sporozoites") in the mosquito's salivary glands. When the Anopheles mosquito takes a blood meal on another human, the sporozoites are injected with the mosquito's saliva and start another human infection when they parasitize the liver cells.

Thus the mosquito carries the disease from one human to another (acting as a "vector"). Differently from the human host, the mosquito vector does not suffer from the presence of the parasites.

Schema of the Life Cycle of Malaria

--Click to Enlarge

The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host . Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ). Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites . Some parasites differentiate into sexual erythrocytic stages (gametocytes) . Blood stage parasites are responsible for the clinical manifestations of the disease.

The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal . The parasites’ multiplication in the mosquito is known as the sporogonic cycle . While in the mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes . The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts . The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.

Human Hosts
Humans infected with malaria parasites can develop a wide range of symptoms. These vary from asymptomatic infections (no apparent illness), to the classic symptoms of malaria (fever, chills, sweating, headaches, muscle pains), to severe complications (cerebral malaria, anemia, kidney failure) that can result in death. The severity of the symptoms depends on several factors, such as the species (type) of infecting parasite and the human's acquired immunity and genetic background.

Malaria Parasites
Four species of malaria parasites can infect humans under natural conditions: Plasmodium falciparum, P. vivax, P. ovale and P. malariae. The first two species cause the most infections worldwide. Plasmodium falciparum is the agent of severe, potentially fatal malaria, causing an estimated 700,000 - 2.7 million deaths annually, most of them in young children in Africa. Plasmodium vivax and P. ovale have dormant liver stage parasites ("hypnozoites") which can reactivate ("relapse") and cause malaria several months or years after the infecting mosquito bite. Plasmodium malariae produces long-lasting infections and if left untreated can persist asymptomatically in the human host for years, even a lifetime.

Anopheles Mosquitoes
Malaria is transmitted among humans by female mosquitoes of the genus Anopheles. Female mosquitoes take blood meals to carry out egg production, and such blood meals are the link between the human and the mosquito hosts in the parasite life cycle. Of the approximately 430 known species of Anopheles, only 30-50 transmit malaria in nature. The successful development of the malaria parasite in the mosquito (from the "gametocyte" stage to the "sporozoite" stage) depends on several factors. The most important is ambient temperature and humidity (higher temperatures accelerate the parasite growth in the mosquito) and whether the Anopheles survives long enough to allow the parasite to complete its cycle in the mosquito host ("sporogonic" or "extrinsic" cycle, duration 10 to 18 days). Differently from the human host, the mosquito host does not suffer noticeably from the presence of the parasites

Levels of Prevention

Prevention of malaria can aim at either:

•preventing infection, by avoiding bites by parasite-carrying mosquitoes, or
•preventing disease, by using antimalarial drugs prophylactically. The drugs do not prevent initial infection through a mosquito bite, but they prevent the development of malaria parasites in the blood, which are the forms that cause disease. This type of prevention is also called "suppression."

Prevention and Control in Endemic Areas
Prevention is an important component of malaria control in endemic countries. It is achieved through:

•vector control
•personal protection measures such as insecticide-treated bed nets
•preventive treatment with antimalarial drugs of vulnerable groups such as pregnant women, who receive intermittent preventive treatment.

Prevention in Travelers
Travelers from non-endemic countries should take precautions against acquiring malaria when they visit a malaria risk area.

Diagnosis and Treatment of Malaria

Diagnosis

Malaria must be recognized promptly in order to treat the patient in time and to prevent further spread of infection in the community.

Malaria can be suspected based on the patient's symptoms and the physical findings at examination. However, for a definitive diagnosis to be made, laboratory tests must demonstrate the malaria parasites or their components.

Diagnosis of malaria can be difficult:
•Where malaria is not endemic any more (such as the United States), health care providers are not familiar with the disease. Clinicians seeing a malaria patient may forget to consider malaria among the potential diagnoses and not order the needed diagnostic tests. Laboratorians may lack experience with malaria and fail to detect parasites when examining blood smears under the microscope.

•In some areas, malaria transmission is so intense that a large proportion of the population is infected but not made ill by the parasites. Such carriers have developed just enough immunity to protect them from malarial illness but not from malarial infection. In that situation, finding malaria parasites in an ill person does not necessarily mean that the illness is caused by the parasites.

•In many malaria-endemic countries, lack of resources is a major barrier to reliable and timely diagnosis. Health personnel are undertrained, underequipped and underpaid. They often face excessive patient loads, and must divide their attention between malaria and other equally severe infectious diseases such as pneumonia, diarrhea, tuberculosis and HIV/AIDS.

Clinical Diagnosis

Clinical diagnosis is based on the patient's symptoms and on physical findings at examination.

The first symptoms of malaria (most often fever, chills, sweats, headaches, muscle pains, nausea and vomiting) are often not specific and are also found in other diseases (such as the "flu" and common viral infections). Likewise, the physical findings are often not specific (elevated temperature, perspiration, tiredness).

In severe malaria (caused by Plasmodium falciparum), clinical findings (confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties) are more striking and may increase the suspicion index for malaria.

Thus, in most cases the early clinical findings in malaria are not typical and need to be confirmed by a laboratory test.

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