The hardest hit regions are Africa, Asia and South America. Sub-Saharan Africa is suffering the most from this disease, with 90% of all malarial deaths occurring here. Children, pregnant women and refugees are the most vulnerable to malaria. Malaria is caused by protozoan parasites of the genus Plasmodium. There are four types of these parasites that are responsible for human infections: Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax. Of these, P. falciparum causes 80% of malaria infections and over 90% of malaria deaths worldwide. The vector of this disease is the Anopheles species of mosquito. Only the female mosquito carries malaria because they feed on blood (male mosquitoes feed only on plant juices). When a mosquito infected with malaria pierces human skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver. Within 30 minutes of being introduced into the human host, the sporozoites infect the cells of the liver, called hepatocytes, multiplying asexually for 6–15 days. These sporozoites then differentiate which yield thousands of merozoites, which rupture out of their host cells in the liver and escape into the blood and infect red blood cells. The merozoites continue to reproduce asexually within the red blood cells, occasionally breaking out of a cell to infect more red blood cells. Some P. ovale and P. vivax sporozoites do not develop straight away into exoerythrocytic-phase merozoites, but produce hypnozoites which remain dormant for periods ranging from several months (6–12 months is common) to as long as five years. After a period of dormancy, they reactivate and produce merozoites. The parasite is relatively protected from attack by the body's immune system because it spends most of its human life cycle within the liver and blood cells which makes it relatively invisible to the body’s defense system. However, circulating infected blood cells are destroyed in the spleen so to avoid elimination, the P. falciparum parasite displays adhesive proteins on the surface of the infected red blood cells, causing them to stick to the walls of small blood vessels, thereby preventing the parasite from passing through general circulation and the spleen. To prevent the host’s immune system from detecting the protein disguise and developing antibodies, the parasite changes the surface protein frequently thereby staying one step ahead of the immune system. Some merozoites turn into male and female gametocytes. If a mosquito bites an infected person, it may pick up gametocytes with the blood, and fertilization occurs in the mosquito's gut which means the mosquito is the definitive host of the disease. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Symptoms After an incubation period of several days in the liver, blood-stage parasites are released that subsequently enter, develop in, and ultimately rupture red blood cells. It is this stage of the parasite's life cycle that results in the symptoms associated with malaria. Just as with typhoid fever, the initial symptoms of malaria are non-specific, generally including fatigue, fever, shivering, joint pain, headache, muscle pain, and gastrointestinal symptoms. Liver enlargement can also occur among young children, while jaundice may occur in adults. Malaria also has classic paroxysms, where fever spikes and chills occur at regular intervals, which could help in diagnosis but are unusual and suggest infection with P. vivax or P. ovale (White & Breman, 2005). These symptoms disappear quickly when the parasite is killed. Left untreated, falciprum malaria may lead to coma or death (Bell et al., 2006), if appropriately treated it carries a mortality rate of 1-3%. However, once vital-organ dysfunction occurs or the proportion of erythrocytes infected increases to >3%, the mortality rate rises steeply, for example, severe and cerebral malaria carries a fatality rate of 10-30% or higher (National Institute of Allergies and Infectious Diseases, 2002). Other features include hypoglycemia, particularly problematic in children and pregnant women and renal impairment which exists mostly in adults (White & Breman, 2005). The specific immune response to malaria eventually controls the infection and, with exposure to sufficient strains, confers protection from high-level parasitemia and disease but not from infection. Therefore asymptomatic parasitemia is commong among adults and older children living in hyperendemic areas (White & Breman, 2005). Treatment: Once malaria is diagnosed, there are several medications that may be taken to counter the disease including quinine and artemether-lumefantrine. The most common drug for malaria in the past was chloroquine however, due to widespread use, the P. falciparum parasite gained resistance to the anti-malaria drug, rendering it useless against the most deadly strain of the disease in most malaria endemic areas. To avoid drug resistance it is recommended that a cocktail of drugs be used, however this significantly raises the cost of treatment. Prevention and protection Certain genetic factors lend protection to malaria and the geographic distribution of some disorders is actually close to that of malaria. This likely means that disorders such as sickle cell disease, thalassemia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more prevalent. The best known example is of HbA/S heterozygotes (sickle cell trait), who have a lower risk of dying from severe falciparum malaria. This is one of the best known instances of heterozygote advantage. Many drugs have also been developed for the prevention (prophylaxis) of malaria, not only for therapy. Drugs such as doxycycline and mefloquine may be taken daily or weekly, respectively, in small doses for prevention and in larger doses to treat the disease. The use of prophylactic drugs is not practical for full time residents of malaria endemic regions because of the high cost of drugs, possibility of resistance accumulation and unknown long term side effects. The complexity of the immune response in malaria, the sophistication of the parasites' evasion mechanisms, and the lack of a good in vitro correlate with clinical immunity have all slowed progress toward an effective vaccine though many researchers are currently working to develop one. Other prevention techniques are currently being used and researched in addition to treatment and prevention drugs. Much work is being focused on the vector of malaria; the mosquito. Mosquito nets (treated with insecticide) are being promoted as a more affordable way to prevent malaria by keeping individuals from being bitten and infected.