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 common species that cause malaria, the most serious type is Plasmodium falciparummalaria. It can be life-threatening. However, another relatively new species, Plasmodium knowlesi, is also a dangerous species that is typically found only in long-tailed and pigtail macaque monkeys. Like P. falciparum, P. knowlesimay be deadly to anyone infected.
The other three common species of malaria (P. vivax, P. malariae, and P. ovale) are generally less serious and are usually not life-threatening. It is possible to be infected with more than one species of Plasmodium at the same time.
Currently, about 2 million deaths per year worldwide are due to Plasmodiuminfections. The majority occur in children under 5 years of age in sub-Saharan African countries. There are about 400 million new cases per year worldwide. Most people diagnosed in the U.S. obtained their infection outside of the country, usually while living or traveling through an area where malaria is endemic.
The life cycle of the malaria parasite (Plasmodium) is complicated and involves two hosts, humans and Anopheles mosquitoes. The disease is transmitted to humans when an infected Anopheles mosquito bites a person and injects the malaria parasites (sporozoites) into the blood.
Sporozoites travel through the bloodstream to the liver, mature, and eventually infect the human red blood cells. While in red blood cells, the parasites again develop until a mosquito takes a blood meal from an infected human and ingests human red blood cells containing the parasites. Then the parasites reach the Anopheles mosquito's stomach and eventually invade the mosquito salivary glands.
When an Anopheles mosquito bites a human, these sporozoites complete and repeat the complex Plasmodium life cycle. P. ovale and P. vivax can further complicate the cycle by producing dormant stages (hypnozoites) that may not develop for weeks to years.
The symptoms characteristic of malaria include flulike illness with fever, chills, muscle aches, and headache. Some patients develop nausea, vomiting, cough, and diarrhea. Cycles of chills, fever, and sweating that repeat every one, two, or three days are typical. There can sometimes bevomiting, diarrhea, coughing, and yellowing (jaundice) of the skin and whites of the eyes due to destruction of red blood cells and liver cells.
People with severe P. falciparum malaria can develop bleeding problems,shock, liver or kidney failure, central nervous system problems, coma, and can die from the infection or its complications. Cerebral malaria (coma, oraltered mental status or seizures) can occur with severe P. falciparuminfection. It is lethal if not treated quickly; even with treatment, about 15%-20% die.
Humans develop malaria when infected with one of the four protazoan parasites from the genus Plasmodium.
The four species include:
- Plasmodium falciparum.
- Plasmodium vivax.
- Plasmodium ovale.
- Plasmodium malaria.
- P. falciparum is the most widespread and dangerous of the four.
Transmission of malaria is affected by climate and geography, and often coincides with the rainy season. We become infected with the parasite from anopheline mosquitos. The malaria protazoa develops in the gut of the mosquito and is passed to humans in the saliva of the insect as it draws a person's blood.
The parasite travels to the liver of the human through the blood stream. Here, the Plasmodium multiplies. After 9-16 days, the protazoa return to the blood supply, where they penetrate red blood cells. The parasite then causes red blood cells to break down.
Three main factors determine treatments: the infecting species of Plasmodium parasite, the clinical situation of the patient (for example, adult, child, or pregnant female with either mild or severe malaria), and the drug susceptibility of the infecting parasites. Drug susceptibility is determined by the geographic area where the infection was acquired.
Different areas of the world have malaria types that are resistant to certain medications. The correct drugs for each type of malaria must be prescribed by a doctor who is familiar with malaria treatment protocols. Since people infected with P. falciparum malaria can die (often because of delayed treatment), immediate treatment for P. falciparum malaria is necessary.
Mild malaria can be treated with oral medication; severe malaria (one or more symptoms of either impaired consciousness/coma, severe anemia, renal failure, pulmonary edema, acute respiratory distress syndrome, shock, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria [hemoglobin in the urine], jaundice, repeated generalized convulsions, and/or parasitemia [parasites in the blood] of > 5%) requires intravenous (IV) drug treatment and fluids in the hospital.
Drug treatment of malaria is not always easy. Chloroquine phosphate (Aralen) is the drug of choice for all malarial parasites except for chloroquine-resistant Plasmodium strains. Although almost all strains of P. malariae are susceptible to chloroquine, P. falciparum, P. vivax, and even some P. ovale strains have been reported as resistant to chloroquine. Unfortunately, resistance is usually noted by drug-treatment failure in the individual patient.
There are, however, multiple drug-treatment protocols for treatment of drug-resistant Plasmodium strains (for example, quinine sulfate plus doxycycline [Vibramycin, Oracea, Adoxa, Atridox] or tetracycline[Achromycin], or clindamycin [Cleocin], or atovaquone-proguanil [Malarone]). There are specialized labs that can test the patient's parasites for resistance, but this is not done frequently.
Consequently, treatment is usually based on the majority of Plasmodium species diagnosed and its general drug-resistance pattern for the country or world region where the patient became infested. For example, P. falciparum acquired in the Middle East countries is usually susceptible to chloroquine, but if it's acquired in sub-Sahara African countries, it's usually resistant to chloroquine. The WHO's treatment policy, recently established in 2006, is to treat all cases of uncomplicated P. falciparum malaria with artemisinin-derived combination therapy (ACTs).
ACTs are drug combinations (for example, artesunate-amodiaquine, artesunate-mefloquine, artesunate-pyronaridine, dihydroartemisinin-piperaquine, and chlorproguanil-dapsoneartesunate) used to treat drug-resistant P. falciparum. Unfortunately, as of 2009, a number of P. falciparum-infected individuals have parasites resistant to ACT drugs.
New drug treatments of malaria are currently under study becausePlasmodium species continue to produce resistant strains that frequently spread to other areas. One promising drug class under investigation is the spiroindolones, which have been effective in stopping P. falciparumexperimental infections.