Malaria – Causes, Signs and symptoms

Malaria

Also called: Paludism, Plasmodium Infection, Jungle Fever, Malaria Disease

Reviewed By:
Vikram Tarugu, M.D., AGA, ACG

Summary

Malaria is a serious tropical disease that can be fatal. It is endemic to more than 100 countries and kills more than 1 million people annually according to the World Health Organization (WHO). Many of the deaths occur after the first exposure of children to the parasite responsible for the disease. Travelers to these areas may also develop malaria with the potential of severe symptoms due to their lack of prior infection.

A single-cell parasite of the genus Plasmodium is responsible for malaria. It is transmitted primarily by mosquitoes and infects the liver and red blood cells. As the parasite spreads through the body, the disease typically progresses from chills to fever to profuse sweating. Symptoms may fade but are likely to recur after two to three days.

Five species of the Plasmodium parasite cause malaria. The severity and recurrence of malaria depend largely on which species caused the infection. Plasmodium falciparum can cause severe symptoms and complications and is responsible for the majority of malaria deaths. Infection by three other parasite species (P. vivax, P. malariae, P. ovale) leads to less severe symptoms, but they may live for years in the body without causing obvious disease. A fifth species, P. knowlesi, was once believed to be restricted to monkeys but is now known to also cause disease in humans.

Early diagnosis of malaria is important for proper treatment. Because of the disease’s potential severity, patients suffering from flu-like symptoms within a year of visiting an area where malaria is endemic should consult their physician. The disease may be confirmed by identifying the parasite in a blood sample. This also allows the specific parasite to be determined, which is important for prescribing the right medication for treatment.

Malaria can often be prevented, especially among travelers, by taking proper measures. Prophylactic, or preventative, antimalarial medicines taken before, during and after visiting an endemic area reduce the risk of being infected. Other efforts focus on reducing mosquito bites to prevent transmission. These include covering skin with clothing, using effective insect repellent and sleeping under bed netting.

Malaria is a disease endemic to many tropical and subtropical countries. While many adults in these areas may develop immunity to the disease-causing parasite, severe illness tends to affect children and travelers to these regions. With proper preventative measures, the risk to travelers of developing malaria is greatly reduced. The prognosis after infection can also be greatly improved with early diagnosis and treatment.

About malaria

Malaria is an infectious disease spread by mosquitoes. It occurs mainly in rural settings but can also impact urban areas. Malaria is most often found in areas with low altitudes, warm temperatures and high humidity. These offer the best breeding conditions for the mosquitoes that spread the disease.

The disease is endemic to more than 100 tropical and subtropical countries and infects 300 million to 500 million people each year according to the World Health Organization (WHO). Of those infected, WHO estimates more than 1 million die each year. Most deaths occur among children who are 5 years old or younger.

Malaria can also occur in countries where it is not endemic. When outbreaks occur in temperate areas, they are often limited by the onset of colder weather as seasons change and mosquitoes become dormant.

Within the United States, approximately 1,300 cases of malaria are diagnosed and reported to the U.S. Centers for Disease Control and Prevention (CDC) each year. The majority are in travelers returning from areas where the disease is endemic.

Malaria results from infection by a single-cell parasites of the genus Plasmodium. While there are more than 100 species of this parasite, only four commonly infect humans and cause malaria. A fifth species, once thought to be isolated to monkeys, has recently been discovered to also cause disease in people. The parasites act in different ways in the body and more than one may be present at a time.

The life cycle of the Plasmodium parasites responsible for malaria depends on moving between mosquito and human hosts. After biting an infected person, mosquitoes carry the parasite but show no signs of disease. Within 10 to 18 days the Plasmodium is in the mosquito’s saliva and can be transmitted. Following a bite, Plasmodium moves through the bloodstream to the person’s liver. Depending on the species, it may stay dormant or begin to multiply within the liver cells. If the parasite multiplies, it eventually causes the infected cell to burst. The offspring then move into the bloodstream where they infect red blood cells. After they are in the bloodstream, the parasites can be transmitted through additional mosquito bites or other means of fluid exchange.

Within red blood cells, the malaria parasites consume proteins and hemoglobin and continue to multiply. Eventually the cell ruptures and the parasites move on to infect others. This cycle continues and causes relapses of symptoms every two to three days. It only stops with medical treatment or a response from the body’s immune system.

Repeated infection allows the body to develop partial immunity or resistance to the disease. Children who survive malaria are less likely to develop severe infections later in life. This immunity fades without continued exposure to the parasite, meaning former residents returning to endemic areas are at risk of becoming ill.

There is also evidence that sickle cell anemia provides some protection from malaria. Sickle cell anemia is a painful, inherited condition in which the red blood cells become abnormally shaped. It is believed that Plasmodium parasites are unable to infect the misshapen cells. Despite the pain and serious complications caused by sickle cell anemia, patients with the disease may live longer than those without it in areas where malaria is prevalent.

Types and differences of malaria

There are five species of Plasmodium parasites that infect people and cause malaria. Each affects the body in different ways, but more than one may be present at a time. They vary in geographic distribution and are distinguishable under a microscope, which is important for treatment. The parasites responsible for malaria in humans are the following:

  • Plasmodium falciparum. This parasite causes the most malaria-related deaths and possibly the most drug-resistant infections. Symptoms develop suddenly and can be severe. It is found throughout much of Africa, Southeast Asia, Oceania (the islands of the Pacific Ocean) and South America. It also occurs in Haiti and the Dominican Republic.
  • Plasmodium vivax. The most widespread of the parasites, it is found throughout much of tropical Asia, Central America, the Middle East and India. It is responsible for most cases of malaria diagnosed in the United States. After infection, it may become dormant within the liver for intervals of up to two years. Even with treatment, this species may cause relapses for several years.
  • Plasmodium malariae. Years and possibly decades can pass between infection with this species and symptoms of disease, which tend to be mild. It is found in parts of Africa and Asia. This species is also known to cause a severe kidney disease known as nephrotic syndrome.
  • Plasmodium ovale. Infection by this parasite is rare and mainly occurs in West Africa. Like P. vivax, after initial infection and disease, it can also stay dormant in the liver.
  • Plasmodium knowlesi. Once believed to only infect monkeys, it is now known to also cause disease in humans. Under a microscope, the parasite appears similar to P. malariae, but it causes more severe disease. Human infections have been reported in Malaysia and Thailand.

Risk factors and causes of malaria

The greatest risk factor for malaria infection is living in or visiting a tropical or subtropical area where the disease is endemic. Populations most at risk of severe malaria symptoms include:

  • Children. The body’s first exposure to malaria is often the most severe. Of those who die each year from the disease, the U.S. Centers for Disease Control and Prevention (CDC) estimates 75 percent are children from Africa.
  • Pregnant women. Symptoms of malaria, especially when caused by Plasmodium falciparum, tend to be more severe in pregnant women. The disease can also cause premature birth, miscarriage and stillbirth. The parasite can be passed to the fetus.
  • Travelers. Much like children, travelers may lack prior exposure to malaria parasites. This makes them more likely to develop the disease if infected while visiting an area where the disease occurs. The areas of greatest transmission include Oceania (e.g. Papua New Guinea, Solomon Islands), sub-Saharan Africa, India, Southeast Asia, South American and Central America. Due to an incubation period of 10 to 16 days, symptoms may not develop until after the traveler has left the area where the infection took place. Some travelers may not manifest symptoms for months after leaving the endemic area.

Malaria results from the transfer of the Plasmodium parasite through blood. Possible transmission routes include:

  • Mosquito bite. The parasite moves from an infected person to a mosquito while the insect is feeding. Inside the mosquito, it moves from the gut to the saliva where it can infect the next person bitten. Other than Plasmodium knowlesi, the parasites responsible for malaria only cause disease in humans.
  • Mother to fetus. Congenital malaria is transferred from a pregnant woman to her fetus. The newborn baby may develop serious symptoms of the disease within days or weeks of birth.
  • Contaminated needles or syringes. Sharing or reusing needles or syringes can pass infected blood from one person to another.
  • Blood transfusion. This is a rare cause of malaria transmission. In the United States, people who have been in areas where malaria is endemic or have been treated for the disease are prevented from donating blood for one to three years.

Signs and symptoms of malaria

After an incubation period of 10 to 16 days, malaria often causes a specific progression of symptoms. The first stage is marked by chills, which may occur in conjunction with headache, nausea and vomiting. Following the chills, a fever typically develops. This is followed by profuse sweating. Other possible symptoms include muscle aches, fatigue, anemia and jaundice (yellowing of the skin).

Depending on which parasite species is responsible for the disease, symptoms may fade but will typically recur. The period between symptoms is often two to three days. In the cases of Plasmodium vivax and P. ovale, the parasite may be dormant for years before recurrence. While the symptoms of most forms of malaria will pass without treatment, those caused by P. falciparum often continue and may cause severe complications (e.g., kidney failure, coma) and death. When the disease affects the brain and central nervous system, it is termed cerebral malaria and can be fatal without treatment.

The symptoms of malaria may easily be confused with those caused by the flu. Due to its potential severity, patients suffering from similar symptoms within a year of visiting an area where malaria is endemic should see their physician.

Diagnosis and treatment for malaria

Diagnosis of malaria may involve a medical history and physical examination. The medical history will likely include questions on symptoms, including their duration, severity and progression. The physical exam will look for signs and symptoms that may not have been apparent to the patient.

In the United States, health providers may not be familiar with the signs and symptoms of malaria. This may lead to misdiagnosis of disease or delay its detection. To aid the physician in correctly diagnosing the condition, patients are encouraged to report recent travel to any tropical or subtropical areas. This can be especially important with Plasmodium falciparum infection, in which early diagnosis can be life saving.

If malaria is suspected based on the patient’s symptoms and recent travels, the physician will likely take a blood sample. A blood smear is examined under a microscope to confirm parasite presence and determine the species. Other methods to diagnose malaria are available but, in general, have limited use. These include:

  • Polymerase chain reaction (PCR). Detects the genetic code of the infecting parasite. Can identify one or more Plasmodium species present.
  • Antigen detection. Useful for confirming infection, but these field tests have limited ability to identify the parasite species. They are not approved for use in the United States.
  • Serological assay. Several methods test blood serum for antibodies to malaria. Problems with some of these tests include false positives due to prior infection and lack of sensitivity to some Plasmodium species.

Of the methods available, examining blood using a microscope generally provides the most accurate results. This not only allows the disease to be confirmed, but also the parasite species to be identified. This is important for choosing the proper treatment.

Many treatment options for malaria have been developed. Antimalarial medications kill the parasites within the body. Some are effective only against certain species of parasite, while others only work against populations that have not developed resistance to the recommended medications. This means the physician needs to know which species is responsible for the disease and where the infection may have taken place. In addition, the patient’s age and degree of illness are also considered in deciding which drug to use. Possible antimalarial medications include:

  • Chloroquine and hydroxychloroquine. These were once the most commonly used medications to treat malaria. Due to spreading resistant strains of the parasite, they are now used primarily for patients infected in the Caribbean and Central America. Side effects may occur and include dizziness, blurred vision and headache.
  • Mefloquine. Effective against most Plasmodium species resistant to chloroquine. Some populations of P. falciparum found in Africa and Southeast Asia have developed resistance to this medication. Side effects are rare, but may be severe. They can include light headedness, bad dreams, paranoia, seizures and psychoses. It is not recommended for patients who suffer from psychiatric disorders or convulsions. When given to prevent malaria, patients normally begin taking this medication several weeks in advance to monitor for severe side effects.
  • Atovaquone-proguanil. Widely used to treat and prevent malaria in areas where the parasite has developed resistance to other medications. Side effects tend to be minor and may include abdominal pain, nausea, vomiting, headache and rash. It serves as an alternative medication for patients who cannot tolerate or have severe side effects from mefloquine.
  • Doxycycline. Works against all types of malaria. It can cause skin reactions when the patient is exposed to the sun. May be used in people traveling to Thailand, Myanmar or Cambodia.
  • Sulfadoxine-pyrimethamine. Used to treat infections in areas where malaria parasites are resistant to chloroquine. Can cause severe reactions in patients and is not routinely recommended.
  • Primaquine. Used to treat infection by P. vivax or P. ovale. It is not recommended for people who are pregnant or suffer from G6PD (glucose-6-phosphate dehydrogenase) enzyme deficiency.

Extensive treatment may be required to completely remove the malaria parasites. This may include taking medication regularly for four months. Malaria reoccurrence is common and will require additional medication.

In areas where malaria is not endemic, such as the United States, treatment often requires hospitalization. Within the hospital, medications can be administered through oral or intravenous (I.V.) routes. Outside the United States, medications may also be provided in suppository form.

Researchers continue to investigate new methods of treating malaria, such as the development of new, more powerful medications with fewer side effects, less risk of resistance and lower costs.

Prevention methods for malaria

For those traveling to areas where malaria may be present, a few steps may help reduce the chance of infection. The U.S. Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) provide information on areas where malaria and other tropical diseases are endemic, as well as areas of current outbreaks. If visiting one of these countries, patients should discuss their travel plans with their physician at least four weeks before travel.

Prophylactic drugs may be prescribed to help the body fight parasite infection. These medications are primarily the same ones recommended for treating the disease. While they are not completely effective, according to the CDC, approximately 90 percent of United States citizens who develop malaria during their travels either took the wrong or no medications to prevent the disease.

During a trip, travelers may take several steps to reduce their chance of being infected. These include:

  • Continuing medication. Prophylactic drugs prescribed to prevent malaria may need to be continued during and after the patient’s travels.

  • Covering skin. Light-colored, long-sleeved shirts and long pants reduce the amount of skin where mosquitoes can bite.

  • Insect repellant. Applying effective spray (such as one containing DEET) on exposed skin may help reduce the number of mosquito bites.

  • Bed nets. When treated with insecticides and tucked under the mattress, bed nets will help prevent mosquitoes from biting during sleep.

In addition, many mosquito species are most active at night. Travelers who limit their exposure during evening hours may reduce their risk of infection with malaria.

Both governmental and nongovernmental agencies continue to develop malaria eradication programs in areas where the disease is endemic, especially Africa. Researchers are investigating many potential ways to prevent or eliminate the spread of the disease, ranging from potential vaccinations to the manipulation of the mosquitoes the parasites rely upon.

In 2006, the WHO approved the use of dichloro-diphenyl-trichloroethane (DDT), for indoor use to fight malaria. DDT is an insecticide that was used in large-scale outdoor insect abatement programs from the 1930s through the 1970s. However, research suggested that DDT was detrimental to wildlife such as birds and fish and could potentially threaten humans as it entered the food chain.

DDT was banned in many countries, including the United States, in the early 1970s. Its use against malaria has remained controversial, although the controversy is generally associated with its agricultural use. Indoor spraying, the practice the WHO endorsed, has proven effective in reducing home mosquito populations without affecting other wildlife or adversely affecting humans.

Questions for your doctor regarding malaria

Preparing questions in advance can help patients have more meaningful discussions with their physician regarding their conditions. Patients may wish to ask their doctor the following questions related to malaria:

  1. Am I at risk for malaria?
  2. What are the different types of malaria?
  3. How is malaria spread?
  4. What steps can my family and I take to prevent malaria infection during our travels?
  5. How long after infection does it take for the disease to cause symptoms?
  6. What early signs and symptoms of malaria should I be aware of?
  7. What are my treatment options for malaria?
  8. Does treatment for malaria require hospitalization?
  9. Are there potential side affects related to malaria treatment medications?
  10. Will treatment for malaria prevent its recurrence?
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