Malaria

• Malaria is a disease that can be transmitted to people of all ages. Malaria is caused by parasites of the genus Plasmodium that are spread from one individual to another through the bites of infected mosquitoes.
• The common first symptoms include fever, headache, chills, and vomiting. These symptoms appear 10-15 days after an individual is infected. If not treated promptly with effective medicines, malaria can cause severe illness that is often fatal.
• Malaria transmission differs in intensity and regularity depending on local factors such as rainfall patterns, proximity of mosquito breeding sites, and mosquito species. The Anopheles mosquito, or more commonly referred to as the "common malaria" mosquito, transmits the disease of malaria. Some regions are endemic areas and have a fairly constant number of cases throughout the year. Other areas have "malaria" seasons, usually coinciding with the rainy season. The rainy season provides more places for standing water where the mosquito can lay eggs.
• Large and devastating epidemics can occur in areas where people have had little contact with the malaria parasite, and therefore have little or no immunity. These epidemics can be triggered by weather conditions and further aggravated by natural disasters.
• About 40% of the world's population, largely living in undeveloped countries, is at risk of malaria. Most cases and deaths are in sub-Saharan Africa where one in every five (20%) childhood deaths is due to the effects of the disease, such as dehydration. Every 30 seconds, a child in Africa dies from malaria. However, Asia, Latin America, the Middle East, and parts of Europe are also affected. Of these 2.5 billion people at risk, more than 500 million become severely ill with malaria every year and more than one million die from the effects of the disease.
• Most American cases of malaria develop in travelers who have recently returned from parts of the world where malaria is widespread. If an individual is traveling to malaria-endemic places, it is recommended by healthcare professionals to take precautions before, during, and after the trip. Bednets, insecticides and antimalarial drugs are available for both the prevention and treatment of malaria.

• Plasmodium is a genus of parasitic protozoa that causes malaria. The four species known to cause malaria in humans are:
• Plasmodium falciparum
  : P. falcatum, predominant in Africa, produces the most severe symptoms and is responsible for most malaria deaths.
• Plasmodium vivax
  : P. vivax, found mostly in tropical areas of Asia, produces less severe symptoms but can remain in the liver and cause relapses for up to three years.
• Plasmodium malariae
  : P. malariae, found in Africa, can cause typical malaria symptoms, but on rare occasions it can remain in the bloodstream for years without producing symptoms. In these cases, is it possible to pass on the parasite to a mosquito or to another person through a blood transfusion.
• Plasmodium ovale
  : P. ovale is found mostly in West Africa. Although infections with P. ovale are rare, relapses may occur.
• The process of transmission:
  In nature, malaria parasites spread by successively infecting 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 blood cells. Successive broods of parasites grow inside the red blod cells and destroy them, releasing daughter parasites ("merozoites") that continue the cycle by invading other red blood 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. Only the female mosquitoes are transmitters because they can penetrate the skin of a person; the male mosquito proboscis is not able to pierce the skin.
• 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.
• 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.
• Typically, signs and symptoms begin 10 days to four weeks after the initial mosquito bite, although they can appear as early as eight days or as late as one year later. Symptoms include: asymptomatic infections (no apparent illness), fever, chills, sweating, headaches, muscle pains, cerebral malaria, anemia and kidney failure and may 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.
• In many cases, medication or the immune system eventually helps stop the infection. But in other cases, particularly in children whose immune systems may not yet have adapted to the parasite, complications of the infection may lead to death. In addition, P. falciparum is capable of invading a much greater number of blood cells than are the other types of Plasmodium, and the infection can be fatal within a few hours of initial red blood cell rupture.
• Other means of transmission:
  A pregnant woman can transmit the infection to her unborn baby. Malaria may be transmitted through blood transfusions. In the United States, steps have been taken to prevent this type of transmission. Individuals who have visited a malaria-endemic area are prohibited from donating blood for a year after returning from the malaria-infected area, or three years if they have been a resident of the malaria-infected area or have been treated for malaria. Malaria can be detected in the blood of an infected individual through blood testing.

• A main risk factor for contracting malaria is living in a region of the world prone to malaria, such as large areas of Central and South America, sub-Saharan Africa, the Indian subcontinent, Southeast Asia, the Middle East, and Oceania.
• Individuals who have little or no immunity to malaria are most at risk for serious illness. Residents of a malaria region may acquire some immunity to the disease during their lifetime, but young children and infants who have yet to acquire any immunity are at risk, as are travelers coming from areas with no malaria.
• A pregnant woman is more vulnerable than other people are to P. falciparum malaria, as is her unborn child.
• Poverty, lack of knowledge, and little or no access to healthcare also contribute to malaria deaths worldwide.
• It is also possible to lose immunity if the individual is no longer frequently exposed to the parasite. Even if the individual has previously lived in a malaria-infected region, it is recommended by healthcare professionals to take antimalarial precautions (such as antimalarial drugs) when returning to such an area after an extended period away.

• Malaria can occur while antimalarial drugs are being taken due to drug resistance (see "Treatment").
• Symptoms of malaria usually appear about 10-14 days after being bittenby an infected mosquito. Symptoms include: sudden, violent chills; intermittent fever; sweating; exhaustion and fatigue; headaches; seizures; and delirium.
• Plasmodium falciparum infections normally take 7-14 days to show symptoms while Plasmodium vivax and Plasmodium ovale normally take 8-14 days (but in some cases can survive for some months in the human horst). Plasmodium malariae infections take 7-30 days.
• Fever in the first week of travel in a malaria-risk area is unlikely to be malaria; however, any traveler feeling ill should seek immediate medical care.

• After noting symptoms and travel history, a doctor will likely obtain a sample (smear) of the individual's blood for observation under a microscope. Two blood samples, taken at six- and 12-hour intervals, can usually confirm the presence of the malaria parasite and its type. It is possible to be infected by more than one Plasmodium at the same time.
• Enzyme-linked immunosorbent assay (ELISA): An enzyme-linked immunosorbent assay (ELISA) test is a blood test that looks for an antigen that is specific to malaria parasites. An antigen is any substance, such as a virus, bacterium, toxin, or foreign protein, which triggers an immune system response in the body.

• Most complications of malaria are associated with infection by Plasmodium falciparum. The extensive destruction of red blood cells that occurs during malaria infection may result in severe anemia. In addition, if parasite-filled blood cells block small blood vessels to the brain (cerebral malaria), swelling of the brain or brain damage may occur. Other complications may include: breathing problems, at times severe in the form of accumulated fluid in the lungs (pulmonary edema); dehydration; liver failure; kidney failure; and rupture of the spleen.
• If untreated, P. falciparum malaria can be fatal within a matter of hours after symptoms appear.

• Because malaria infection often initially appears to be a flu-like illness or some other viral disease, individuals should be wary if they develop an illness with fever while living in a malaria-endemic area or within 12 months after traveling to a high-risk malaria region. It is recommended by healthcare professionals to see a doctor as soon as possible and inform the doctor about the countries that were visited. Left untreated, a malaria infection can cause serious, potentially life-threatening health problems.
• Malaria infection, particularly with Plasmodium falciparum, requires prompt evaluation and treatment. In most cases, doctors can treat malaria effectively with anti-malarial drugs.
• The Centers for Disease Control and Prevention (CDC) recommend that treatment be guided by three main factors: the infecting Plasmodium species, the clinical status of the patient, and the drug susceptibility of the infecting parasites as determined by the geographic area where the infection was acquired.
• According to the CDC's Web site, determination of the infecting Plasmodium species for treatment purposes is important for three main reasons: P. falciparum infections can cause rapidly progressive severe illness or death while the non-falciparum (P. vivax, P. ovale,
  or P. malariae) species rarely cause severe manifestations; P. vivax and P. ovale infections require treatment for the hypnozoite forms that remain dormant in the liver and can cause a relapsing infection; and P. falciparum and P. vivax species have different drug resistance patterns in differing geographic regions.
• The second factor affecting treatment, the clinical status of the patient, is used to categorize patients as having either uncomplicated or severe malaria. Patients diagnosed with uncomplicated malaria can be effectively treated with oral antimalarials. However, patients who have one or more of the following clinical criteria - impaired consciousness/coma, severe normocytic anemia, renal failure, pulmonary edema, acute respiratory distress syndrome, circulatory shock, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria, jaundice, repeated generalized convulsions, and/or parasitemia of greater than five percent - are considered to have manifestations of more severe disease and should be treated aggressively with parenteral antimalarial therapy.
• And lastly, knowledge of the geographic area where the infection was acquired provides information on the likelihood of drug resistance of the infecting parasite enabling the treating clinician to choose an appropriate drug or drug combination and treatment course. If the diagnosis of malaria is suspected and cannot be confirmed, or if the diagnosis of malaria is confirmed but species determination is not possible, the CDC recommends that antimalarial treatment effective against P. falciparum be initiated immediately.
• In the Untied States, malaria is a nationally notifiable disease and all cases should be reported to the individual's state health department. CDC clinicians are on-call 24 hours to provide advice to clinicians on the diagnosis and treatment of malaria and can be reached through the Malaria Hotline.
• Another class of antimalarial drugs, often prescribed in Asia and now in other parts of the world, is derived from artemisinin, a sweet wormwood (Artemesia annua) extract. Primaquine may be given to fight the dormant liver form of the parasite and prevent relapses. However, the CDC has warned against taking primaquine if the individuals is pregnant or has an enzyme deficiency called G6PD (glucose-6-phosphate dehydrogenase) deficiency. Doctors will not use primaquine until the individual has passed a screening test for G6PD deficiency.
• Side effects of antimalarial drugs include nausea, vomiting, and stomach upset. The antimalarial drug mefloquine (Lariam®) has received attention because of reports that it causes panic attacks, hallucinations, anxiety, depression, paranoia, and other mental and mood changes, sometimes lasting for months after the last dose.
• Drug resistance: The history of antimalarial medicine has been marked by a constant struggle between evolving drug-resistant parasites and the search for new drug formulations. Resistance can be caused by mutations in the genetics of the infecting agent, such as the Plasmodium species. The longer the species is exposed to the anti-malarial drug, the more likely the parasite will mutate and become resistant to the drug. In certain parts of the world, for instance, resistance to chloroquine has rendered the drug ineffective. Currently, anti-malaria experts are focusing on therapies that combine artemisinin derivatives with other companion drugs, such as lumefantrine, sulfadoxine-pyrimethamine, amodiaquine (a drug similar to chloroquine), and mefloquine. Artemisin derivatives are not licensed for use in the United States, but are found overseas.

B

Good scientific evidence

• Vitamin A
  : Vitamin A is a fat-soluble vitamin that is derived from two sources: preformed retinoids and provitamin carotenoids. Retinoids, such as retinal and retinoic acid, are found in animal sources like liver, kidney, eggs, and dairy produce. Carotenoids like beta-carotene (which has the highest vitamin A activity) are found in plants such as dark or yellow vegetables and carrots. Limited research suggests that vitamin A may reduce fever, morbidity, and parasite blood levels in patients with malaria (Plasmodium falciparum infection). However, evidence is currently lacking that vitamin A is equivalent or superior to well-established drug therapies used for the prevention or treatment of malaria. Individuals with malaria or living/traveling in endemic areas should speak with a doctor about appropriate measures.
• Vitamin A toxicity, or hypervitaminosis A, is rare in the general population. Vitamin A toxicity can occur with excessive amounts of vitamin A taken over short or long periods of time. Avoid if allergic or hypersensitive to vitamin A. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses; however, vitamin A excess, as well as deficiency, has been associated with birth defects. Excessive doses of vitamin A have been associated with central nervous system malformations. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.

C

Unclear or conflicting scientific evidence

• Andiroba
  : Andiroba oils have been traditionally used to make insect repellant soaps and candles.
• Use cautiously in patients with known allergies or known sensitivities to andiroba, Carapa spp., or its constituents. Avoid in patients with known dermatologic sensitivities, as well as in newborns and infants.
• Berberine
  : Berberine is a bitter-tasting, yellow, plant alkaloid with a long history of medicinal use in Chinese and Ayurvedic medicine. Berberine is present in the roots, rhizomes, and stem bark of various plants including Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). Berberine has also been used historically as a dye, due to its yellow color. Limited available human study has assessed the use of berberine in combination with pyrimethamine in the treatment of chloroquine-resistant malaria. Well-designed clinical trials are still required in this field. Berberine may increase bleeding in sensitive individuals, such as those taking blood-thinning medications including aspirin and warfarin (Coumadin®).
• Avoid if allergic or hypersensitive to berberine, to plants that contain berberine (e.g. goldenseal, coptis, goldenthread, Oregon grape, barberry, or tree turmeric), or to members of the Berberidaceae family. Use cautiously with heart disease, gastrointestinal disorders, blood disorders, leucopenia (abnormally low level of white blood cells), kidney disease, liver disease, lung disorders, cancer, hypertyraminemia (high levels of tyramine), diabetes, or low blood pressure. Use cautiously in children due to lack of safety information. Use cautiously with high exposure to sunlight or artificial light. Use cautiously for longer than eight weeks. Use cautiously if taking anticoagulants, antihypertensives, sedatives, anti-inflammatories, or medications that are broken down by the liver. Avoid if pregnant or breastfeeding. Avoid in newborns.
• Catnip
  : Early studies have assessed the efficacy of catnip oil or its constituents as an insect repellent against mosquitoes. These studies have yielded promising results, however, further research is needed to obtain additional data on the level of effectiveness of catnip oil for this application.
• Avoid if allergic or hypersensitive to catnip, its constituents, or members of the Lamiaceae family. Use cautiously with psychiatric disorders or if taking medications that affect the central nervous system. Avoid if pregnant or breastfeeding.
• Celery
  : Wild celery can be found throughout Europe, the Mediterranean, and parts of Asia. The leaves, stalks, root, and seeds can be eaten. Based on early study, celery extract may be an effective mosquito repellent. Although study results have been promising, additional research is needed in this area.
• Avoid if allergic or hypersensitive to celery (Apium graveolens), its constituents or members of the Apiaceae/Umbelliferae family or with birch pollen-related allergens. Use cautiously if exposed to ultraviolet radiation. Use cautiously with bile secretion disorders. Avoid if eating large amounts of psoralen-containing foods or herbs. Avoid high-celery intake in pregnant patients. Use cautiously if breastfeeding.
• Clove
  : In laboratory and field tests, undiluted clove oil repelled multiple species of mosquitoes for up to two hours. However, undiluted clove oil may also cause dermatitis. Further research is needed to better determine the effectiveness of clove as a mosquito repellant.
• Avoid if allergic to Balsam of Peru, clove, eugenol, or some licorice products and tobacco (clove cigarette) products. Avoid if history of seizures, stroke, or with liver damage. Use cautiously if taking medications for diabetes, bleeding problems, or male impotence. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Use cautiously if driving or operating machinery. Avoid if pregnant or breastfeeding due to insufficient evidence of safety.
• Eucalyptus oil
  : Preliminary research shows that Citriodiol® spray, which contains eucalyptus, may reduce the number of tick bites and thereby tick-borne infections. Additional studies are warranted to better determine the effectiveness of eucalyptus oil as a tick repellant.
• Avoid if allergic to eucalyptus oil or if a history of seizure, diabetes, asthma, heart disease, abnormal heart rhythms, intestinal disorders, liver disease, kidney disease, or lung disease. A strain of bacteria found on eucalyptus may cause infection. Toxicity has been reported with oral and inhaled use. Use cautiously if driving or operating machinery. Avoid with history of acute intermittent porphyria (group of genetic disorders in which substances called porphyrins build up in the blood). Avoid if pregnant or breastfeeding due to insufficient evidence of safety.
• Garlic
  : According to preliminary research, self-reports of tick bites were significantly less in people who received garlic over placebo "sugar" pills. Further well-designed research is needed to better determine the effectiveness of garlic as a tick repellant.
• Avoid if allergic or hypersensitive to garlic or other members of the Lilaceae
  (lily) family (like hyacinth, tulip, onion, leek, chive). Avoid with history of bleeding problems, asthma, diabetes, low blood pressure, or thyroid disorders. Stop using supplemental garlic two weeks before dental/surgical/diagnostic procedures and avoid using immediately after such procedures to avoid bleeding problems. Avoid in supplemental doses if pregnant or breastfeeding due to insufficient evidence of safety.
• Goldenseal
  : Goldenseal (Hydrastis canadensis) is one of the five top-selling herbal products in the United States. However, there is little scientific evidence about its safety or effectiveness. Early study found that berberine, a chemical found in goldenseal, may be beneficial in the treatment of chloroquine-resistant malaria when used in combination with pyrimethamine. Due to the very small amount of berberine found in most goldenseal preparations, it is unclear whether goldenseal contains enough berberine to have these effects.
• Goldenseal may increase bleeding in sensitive individuals, such as those taking blood-thinning medications including aspirin and warfarin (Coumadin®). Avoid if allergic or hypersensitive to goldenseal or any of its constituents, like berberine and hydrastine. Avoid if pregnant or breastfeeding.
• Jojoba
  : Jojoba (Simmondsia chinensis) is a shrub native to deserts in Arizona, California, and Mexico and is also found in some arid African countries. It is traditionally used as a carrier or massage oil. There is currently not enough available evidence to recommend for or against the use of jojoba oil as a mosquito repellent.
• Avoid if allergic or hypersensitive to jojoba, its constituents or members of the Simmondsiaceae family. Avoid oral consumption of jojoba products. Avoid if pregnant or breastfeeding.
• Neem
  : Neem oil and neem cream exhibited protective effects against mosquito bites from various species in non-randomized, controlled studies. However, the studies are limited by small sample size and lack of randomization and blinding. Further research is necessary before a conclusion can be reached on the use of neem as a mosquito repellant.
• Avoid if allergic or hypersensitive to neem (Azadirachta indica) or members of the Meliaceae family. Use cautiously with liver disease. Avoid in children and infants because several cases of death in children from neem oil poisoning have been reported Avoid if pregnant because neem may cause miscarriage. Avoid if breastfeeding due to insufficient evidence of safety.
• Riboflavin
  : Riboflavin (vitamin B2) is a water-soluble vitamin, which is involved in vital metabolic processes in the body, and is necessary for normal cell function, growth, and energy production. Small amounts of riboflavin are present in most animal and plant tissues. Low riboflavin levels have been associated with anti-malarial effects, and anti-riboflavin therapies were proposed in the 1980s, although more recent evidence has challenged this proposed association with malaria.
• Avoid if allergic to riboflavin. Since the amount of riboflavin a human can absorb is limited, riboflavin is generally considered safe. Riboflavin is generally regarded as being safe during pregnancy and breastfeeding when taken at the recommended dosages.
• Sweet annie
  : Sweet annie (Artemisia annua) is also known as Chinese wormwood or sweet wormwood. Although there has been some interest in using sweet annie as an antimalarial therapy, there is currently not enough human evidence to support its use for malaria.
• Avoid if allergic or hypersensitive to sweet annie (Artemisia annua), its constituents, or members of the Asteraceae/Compositae family such dandelion, goldenrod, ragweed, sunflower, and daisies. Use cautiously in patients who are pregnant, taking angiogenic agents, or recovering from surgery or other wounds. Use cautiously if taking cardiotoxic or neurotoxic agents or with compromised cardiac or neural function. Use cautiously if taking immunostimulants or quinolines. Avoid if pregnant or breastfeeding.
• zinc
  : Zinc is necessary for the functioning of over 300 different enzymes and plays a vital role in an enormous number of biological processes. Results are contradictory regarding the effect of zinc on malaria symptoms. Some randomized, double-blind clinical trials suggest no effect of zinc supplementation on the severity of malaria. Other studies suggest that zinc supplementation may reduce the number of stays in the hospital and death rate due to P. falciparum infection. Further well-designed, randomized and controlled trials are required to address these discrepancies.
• Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

• Prevention is based on avoiding exposure to mosquitoes and aggressivelytreating those individuals who are infected. Malaria control programs, such as pesticide use, inmany parts of the world are under-funded and ineffective. Ifan individual is traveling to an area where malaria is common, taking antimalarialdrugs exactly as prescribed by a doctor is important. Also, it is recommended by healthcare professionals to prevent mosquitobites by: closing windows at night if possible; sleeping with a mosquitonet, preferably one containing an insecticide,with the edgestucked under the mattress; covering up the body as much aspossible with clothing; and applying an insect repellent to areasof the body not coveredby clothing.
• For preventive treatment, individuals generally take the prescribed drug one to two weeks before leaving, throughout the trip, and for four weeks after return. Overdose of antimalarial drugs can be fatal, so following the prescription carefully is important. It is also important not to miss doses.
• If the individual is pregnant, avoid traveling to malaria-endemic regions. If this is not possible, a doctor can prescribe an antimalarial drug that is appropriate for each individual, such as chloroquine or mefloquine (during the second or third trimester). Malarone® or doxycycline can harm the fetus.