Plasmodium Falciparum - Malaria

Plasmodium falciparum is the Plasmodium species responsible for 85 % of the malaria cases. The three less common and less dangerous Plasmodium species are: P. ovale, P. malariae and P. vivax. Malaria infects over 200 million people annually, mostly in poor tropical and subtropical countries of Africa. It is the deadliest parasitic disease killing over one million people each year. 90 % of the deaths occur south of the Sahara desert and most are under five-year-old children. In addition to Africa, malaria occurs in South and Southeast Asia, Central and South America, the Caribbean and the Middle East. Even within tropical and subtropical areas, malaria does not usually occur at high altitudes (over 1500 meters), during colder seasons, in countries of successful malaria programs or in deserts.

Life cycle

Malaria is carried by Anopheles mosquitoes. Of the over 400 Anopheles species, only 30–40 can transmit malaria. The infection starts, when a female mosquito injects (in her saliva) "sporozoites" (one form of P. falciparum) into human skin while taking a blood meal. A sporozoite travels (in the bloodstream) into the liver where it invades a liver cell. It matures into a "schizont" (mother cell) which produces 30000–40000 "merozoites" (daughter cells) within six days. The merozoites burst out and invade red blood cells. Within two days one merozoite transforms into a trophozoite, then into a schizont and finally 8–24 new merozoites burst out from the schizont and the red cell as it ruptures. Then the merozoites invade new red cells. P. falciparum can prevent an infected red cell from going to the spleen (the organ where old and damaged red cells are destroyed) by sending adhesive proteins to the cell membrane of the red cell. The proteins make the red cell to stick to small blood vessel walls. This poses a threat for the human host since the clustered red cells might create a blockage in the circulation system.

A merozoite can also develop into a "gametocyte" which is the stage that can infect a mosquito. There are two kinds of gametocytes: males (microgametes) and females (macrogametes). They get ingested by a mosquito, when it drinks infected blood. Inside the mosquito's midgut, male and female gametocytes merge into "zygotes" which then develop into "ookinetes." The motile ookinetes penetrate the midgut wall and develop into "oocysts." The cysts eventually release sporozoites, which migrate into the salivary glands where they get injected into humans. The development inside a mosquito takes about two weeks and only after that time can the mosquito transmit the disease. P. falciparum cannot complete its life cycle at temperatures below 20 °C.

Symptoms

After being bitten by an infected mosquito, symptoms usually begin within 10–30 days. Malaria can be uncomplicated or severe. Symptoms of uncomplicated malaria might include:

• chills
• diarrhea
• fever
• headaches
• muscle pain
• nausea
• sweating
• vomiting
• weakness.

Some less noticeable manifestations:

• enlargement of the spleen or liver
• increased breathing frequency
• mild anemia
• mild jaundice (yellowish eye whites and skin).

The disease can turn into severe malaria, if there are serious organ failures or abnormalities in the bloodstream or metabolism. Symptoms of severe malaria might include:

• breathing difficulties
• coma
• confusion
• death
• focal neurologic signs
• seizures
• severe anemia.

Some less noticeable manifestations:

• abnormalities in blood coagulation
• hemoglobin in the urine
• high acidity of the blood
• hypoglycemia (low blood glucose)
• low blood pressure
• kidney failure.

During pregnancy malaria can lead to premature baby delivery or delivery of a low-birth-weight baby. The infant can get the parasite from the mother and develop the disease. Central nervous system involvement (cerebral malaria) can cause (especially in small children) blindness, deafness, speech difficulty, paralyses and trouble with movements.

Diagnosis

Malaria is usually diagnosed by examining a blood sample under a microscope. There are also test kits that detect antigens of P. falciparum in the patient's blood. These immunologic tests are known as rapid diagnostic tests (RDTs). RDTs can detect two different malaria antigens, one for P. falciparum and the other is found in all four human malaria species. RDTs usually show results in about 20 minutes. It is a good alternative to microscopy, when reliable microscopic diagnosis cannot be done. RDT might not detect some infections, if there are not enough malaria parasites in the patient’s blood. A negative RDT result can be followed up by microscopy. If a patient with positive RDT result is not responding to treatment, another blood sample should be taken. This time using microscopy to determine whether the medicine was appropriate for the Plasmodium species.

Diagnosis can be challenging for many reasons:

• Some health workers in developing countries are insufficiently trained and supervised.
• The microscopes and reagents might be of poor quality and the supply of electricity might be unreliable.
• Some health workers save blood samples until a qualified person is available to perform the microscopy. This delay results sometimes as incorrect diagnosis.
• Many malaria endemic communities do not have the proper diagnostic tools such as microscopes and RDTs.

Treatment

Most malaria deaths occur in rural areas. Quick progression from illness to death can be prevented by fast and effective medication. Patients who have uncomplicated malaria can visit a nearby hospital to get treated and then go home to rest. In emergency cases rectal artesunate drug can be given as a first line treatment (if they cannot be treated orally). Patients with severe malaria can be hospitalized for many days. When treating a malaria patient, the following should be taken into account:

• age and size of the person (to give the correct amount of medication)
• drug allergies or other medications taken by the patient
• health condition, when starting the treatment
• where the person was infected (what Plasmodium species is likely to be responsible and what drug is needed).

P. falciparum and P. vivax have been confirmed to be resistant (in some areas) to many antimalarial drugs. For example, chloroquine resistant strain of P. falciparum has spread to most endemic areas.

Listed below are some drugs that are usually recommended by national malaria control programs. They might not be effective in many parts of the world due to drug resistant strains.

• artemesinin-containing combination treatments (for example, artemether-lumefantrine, artesunate-amodiaquine)
• atovaquone-proguanil
• chloroquine
• doxycycline
• mefloquine
• quinine
• sulfadoxine-pyrimethamine.

Primaquine, is used as an adjunct against certain Plasmodium species. It is active against the dormant liver forms (hypnozoites which are rare/nonexistent with P. falciparum). Primaquine is not recommended for people who are deficient in glucose-6-phosphate dehydrogenase or for pregnant women. Treating all people simultaneously in a population can prevent major malaria epidemics. Unfortunately it can also increase drug resistance of the parasite and complications in those who are glucose-6-phosphate dehydrogenase deficient.

Prevention

Insecticide-treated bed nets may reduce deaths of children under 5 years up to 20 % (according to trials in several African communities). Anopheles mosquitoes usually feed during the night so you can protect yourself by sleeping under a bed net. If everyone in a community has a bed net, the occurrence of malaria can be reduced. Bed nets are usually made of polyester but sometimes cotton, polyethylene, or polypropylene is used instead. All bed nets are treated with pyrethroid insecticides, which have are low health risks to humans but are toxic to insects even at low doses. Pyrethroids do not rapidly wear off, unless exposed to sunlight or washed. "Long-lasting insecticide-treated bed nets" maintain effective levels of insecticide for three years or more. Bed net donations can be made through organizations such as Nothing But Nets and Malaria No More. The price of one bed net is only a few US dollars (which is often too expensive for people in developing countries).

Many malaria-carrying mosquitoes are endophilic, meaning that they typically rest inside the house after taking a blood meal. Indoor Residual Spraying of the walls and other surfaces can kill them reducing the chances that infected mosquitoes spread the disease from one household to another.

Humans living in areas where malaria is common can become partially immune. Travelers, young children, women having their first or second pregnancy and those who are weakened by other diseases (such as AIDS) have little to no immunity against malaria. Recommendations for pregnant women living in malaria endemic areas:

• Eat iron and folate supplements to prevent anemia.
• Get a curative dose of an antimalarial drug at least twice during pregnancy (starting from the second trimester).
• Sleep under an insecticide-treated bed net.

The number of mosquitoes may be controlled by eliminating mosquito larvae before they reach adulthood. Rainfall forms water puddles where mosquitoes lay their eggs and aquatic larvae develop into adults in a few days. Draining or removal of small puddles can reduce the number of mosquitoes near populations. Chemical insecticides can also be applied but might harm the environment. Other methods applied to water:

• insect growth regulators
• oil that suffocates the aquatic larvae
• toxins from the bacterium Bacillus thuringiensis var. israelensis (Bti).

Additional personal protection methods include:

• glass windows (a well-constructed house)
• repellent
• white or light-colored clothes covering most of the body.

Also check out the malaria pictures and videos.