Malaria is a parasitic disease that causes chills, anemia, and fever (1). There are four Plasmodium protozoa (single-celled parasites) which are the causative agents of malaria; Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. P.falciparum is the cause of the majority of infections and is the most lethal (3). The Plasmodium is identified as a Protozoan or Sporozoan species of the Apicomplexa phylum (6). They are not motile in their mature form and are obligate intracellular parasites (6). The Apicomplexans have special organelles at the apex of their cells that contain enzymes to penetrate the host's tissues (6).
Malaria is a very old infection. It is thought that prehistoric men suffered from malaria (4). Malaria is believed to have originated in Africa and, by human migration, it spread to the Mediterranean shores, India, and South East Asia (4). The name is derived from the Italian (mal-aria) meaning "bad air" or also called Roman fever (4). In 1880, Charles-Louis-Alphonse Laveran, a French Army physician in Algeria identified the parasite (7). It was recognized by 1882 that the Anopheles mosquito played a role in transmission and in 1948 all the stages in its life cycle were identified (4, 7).
Malaria is the world's most important tropical disease because it causes more deaths than any other communicable diseases, except for tuberculosis (3). This disease has reached epidemic proportions in many areas of the world (3). The CDC reports that malaria occurs in over 100 countries and affects 40% of the world population (2, 3). Large areas of Central and South America, Hispaniola (Haiti and Dominican Republic), Africa, and the Indian subcontinent, Southeast Asia, the Middle East, and Oceania are considered malaria-risk areas. It is estimated that there are 300-500 million cases a year of malaria resulting in more than 1 million deaths (1). Other figures indicate 1.5-2.7 million deaths where 90% of the cases occur in Africa (1, 5). Children, pregnant women, and non-immune travelers entering endemic areas are high-risk groups (3). It is reported by the World Health Organization (WHO) that malaria kills one child every 30 seconds (3). In the United States, the disease was once common, but mosquito control caused the reported cases to drop below 100 by 1960 (6). In recent years, there has been an increase of malaria cases (6). Each year about 1,200 cases of malaria in the U.S. are diagnosed; however, most cases are due to immigrants and travelers returning from malaria-risk areas, mostly from sub-Saharan Africa and the Indian subcontinent (2, 3).
Humans are reservoirs for the malaria parasite and the Anopheles mosquito is the vector that transmits the disease (6, 8). The life cycle of the Apicomlexan is complex because it involves several hosts: a definitive host where sexual reproduction occurs in the intestine of an Anopheles mosquito and an intermediate host where asexual reproduction of the parasite takes place in the liver and red blood cells of a human host. When a mosquito bites a person with infected blood it will ingest tiny parasites and after a week the mosquito can be infectious (2). The malaria parasite must grow in the mosquito for at least a week before it can cause infection (1). After a week, the mosquito's bite results in parasitic (sporozoites) migration to a person's liver, where they enter the liver's cells to grow and multiply (1, 2). In this period, when the parasites are in the liver, an individual does not feel sick (2). Once the parasites reach maturity they release another form called merozoites and enter the bloodstream to infect the red blood cells (1). The infection of red blood cells may take as little as 8 days or as many as several months (2). Once the parasites are inside the red blood cells they grow rapidly causing rupture and allow the free parasites to infect other red blood cells (1, 2). The rupture may occur in 48-72 hours and the toxins released from the parasite cause a person to feel sick (1, 2). Malaria is also transmitted congenitally, from mother to unborn baby, and by blood transfusions (1). Research indicates that pregnant women are twice as attractive to infected mosquitoes than to non-pregnant women due to a greater volume of exhaled air (21%) and a warmer (0.7 degrees Celsius) skin surface (4). In addition, transmission of malaria is affected by factors such as climate, geography, and rainy seasons (3).
In most cases, symptoms begin 10 days to 4 weeks after infection (2). Symptoms are characterized by fever, shivering, pain in the joints, headache, repeated vomiting, and generalized convulsions (3). Malaria may cause anemia and jaundice due to the loss of red blood cells (3). The P.falciparum may cause kidney failure, mental confusion, coma, and death if it is not treated promptly (2). The malaria P.vivax and P.ovale can relapse because some these parasites can rest in the liver for several months up to 4 years after a person is bitten (2). One these parasites come out of hibernation they begin invading the red blood cells and the individual will become sick again (2).
Malaria is diagnosed by observation of a thick blood smear for Plasmodium (6). Blood (10-15 mm in diameter) is placed on a microscope. It is allowed to dry and a Field's stain is done which uses a poloychrome methylene blue (A) and eosin (B) solutions (4). Parasites are visible under a microscope using an oil immersion or high dry lens (2). This method is effective for identifying the causative Plasmodium parasite of the four types. Recent techniques are based on the "dipstick" format. Tests with the dipstick format include the ICT-Malaria Pf, OptiMALr and the Determine kits (4). These tests are used for detection of the plasmodial histidine rich protein-2 (HRP-2) or parasite-specific lactate dehydrogenase (pLDH) that are present in P.falcriparum infections. The "dipstick" methods are not accurate for detecting other forms of malaria. Dipstick tests are speedy and require less training techniques for viral identification (4).
Virulence for the Plasmodium varies with the type of parasite that causes the malaria infection. The Plasmodium malariae virulence mechanisms include intracellular multiplication and its complex life cycle (8). Virulence mechanisms for the P.vivax are drug resistance, intracellular multiplication, antigenic variations, and persistent liver stages are included because it allows for relapse up to 5 years after elimination of red blood cell stages and clinical cure (8). The P.falciparum is the most pathogenic and its virulence mechanisms include antigenic variations, intracellular multiplication, cytoadherence of infected red blood cells and drug resistance (8). The virulence factor, for the P.falciparum, that causes it to be the most pathogenic is due to the frequent recombination of genes because the chromosome regions cluster together (9). The var genes that encode major variable parasite protein and are expressed at the surface of an infected red blood cell are clustered together allowing recombination frequencies much higher than those expected from homologous crossover alone (9).
Malaria can be treated with prescription drugs (2). Factors such as which kind of malaria, where the patient was infected, the age of the patient, and how severely ill the patient was at start of treatment determines with type of drug and the length of the treatment (2). The P.viax, P. malariae, and P.ovale forms of malaria are treated with Cholorquine. Treatment with the drug Cholorquine (tablet form) is being used of some regions but it is limited in other parts of the world (4). This drug is considered safe for pregnant women, lactating women, and for children (4). Treatment with Cholorquine should begin one week before traveling to a malaria region and continued for four weeks after leaving the region (4). Severe infections of P.falcipaarum malaria are treated in an intensive care setting with intravenous Quinine. Uncomplicated forms of P.flaciparum are treated with Quinine, Malarone TM, or Melfoquine (Larium). Quinine causes patients to develop tinnitus, high-tone hearing loss, nausea, and dysphoria after 2-3 days. Malarone TM is an effective prophylactic with few side effects however it is expensive and has to be taken daily. Melfoquine (Lariam) is widely used because it has a long half-life and only one weekly dose but it causes sides affects associated with sleep disturbances, gastrointestinal disturbances, and dizziness or disturbed sense of balance (4). Anti-malarial drug prophylaxis is difficult due to the growing number of drug resistant strains of P.falciparum now common in South East Asia and in Africa (4). Resistance to the drugs Fansidar, Cholorquine, Maloprim, Lariam, Halofantrine, and Quinine have also been reported (4).
The most recent vaccine, G25, was found to cure malaria (5). This vaccine blocks the ability for the parasite to multiply in the blood cells and prevents the synthesis of a protective membrane (5). The new drug has not shown evidence of resistance by the parasites (5). The G25 has been tested on monkeys thus far and will be available for testing on humans in two years (5). Currently there are no tablet forms available, so it must be taken by injection (5). According to WHO, efforts to development of three main types of malaria vaccines are underway. The "anti-sporoite" vaccine which is designed to prevent infection, the "anti-asexual blood stage" vaccine that is designed to reduce severe and complicated infections, and "transmission-blocking" vaccines that are designed to arrest the development of the parasite in the mosquito which would eliminate the transmission of the disease (3). Other disease prevention research currently underway is the mapping of the malaria genome and seeking ways to inhibit the parasite to travel from the gut of the mosquito to the saliva, rendering it infective to man (3).
There are various methods to prevention of malaria that either target protection against infection or against the development of the disease in infected individuals (3). Methods that protect against infection involve protective measures: protective clothing, repellents with DEET, bed nets, and use of insecticides or environmental management to control transmission (3). Methods that protect against disease but not against infection include prophylaxis. The drugs available can reduce the malaria infections and deaths. Travelers to malaria regions should visit a health care provider 4-6 weeks prior to travel for necessary vaccinations and prescriptions of anti-malarial drugs (2).
REFERENCES
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