Diseases without borders (continued)

Aug. 1, 2010

Description: Malaria is another mosquito-borne disease caused by a parasite. People with malaria often experience fever, chills, and flu-like illness. Left untreated, they may develop severe complications and die.20 An international team of researchers that employed DNA sequencing has found evidence that malaria originated in Africa and that the disease was carried by humans who migrated out of the continent 60,000 years ago. Humans and the malaria parasite also evolved together since this time, researchers say. A broader knowledge of how the parasite's genome differs across continents will aid in the prevention of drug resistance and in the formulation of a vaccine, an expert says.21

Transmission: Different forms of human malaria are caused by five species of the parasite Plasmodium, which are spread by as many as 40 species of the Anopheles mosquito. Effectively addressing malaria requires a fundamental understanding of the complex interactions that occur as the parasite replicates in both the human host and mosquito vector. Malaria elimination and eradication are made even more daunting by the impact of malaria on different populations and age groups, which varies greatly in different epidemiological settings and from region to region.21

Diagnosis: Rapid and accurate diagnosis of malaria is integral to the appropriate treatment of affected individuals and in preventing the further spread of infection in the community. As a national reference center for malaria diagnosis, the CDC provides diagnostic and technical assistance on malaria diagnosis, as well as reference microscopic diagnosis and other specialized tests such as serology and PCR. Additionally, telediagnosis and training are provided for malaria and other parasitic diseases through the website of the CDC's Division of Parasitic Diseases (DPDx) within the National Center for Zoonotic, Vector-borne, and Enteric Diseases.20

Because malaria cases are seen relatively rarely in North America, misdiagnosis by clinicians and laboratorians has been a commonly documented problem in published reports. Malaria, however, may be a common illness in areas where it is transmitted and, therefore, the diagnosis of malaria should routinely be considered for anyone who has traveled to an area with known malaria transmission in the past several months preceding symptom onset.20

Patients suspected of having malaria infection should be urgently evaluated, but treatment for malaria should not be initiated until the diagnosis has been confirmed by laboratory investigations. “Presumptive treatment” without the benefit of laboratory confirmation should be reserved for extreme circumstances (strong clinical suspicion, severe disease, impossibility of obtaining prompt laboratory confirmation, usually by microscopy).20

Laboratory diagnosis of malaria can be made through microscopic examination of thick and thin blood smears. Thick blood smears are more sensitive in detecting malaria parasites because the blood is more concentrated allowing for a greater volume of blood to be examined; however, thick smears are more difficult to read. Laboratories that have limited experience may prefer to use thin smears, which can aid in parasite species identification.20 Blood films need to be read immediately; off-hours, qualified personnel who can perform this function should be on call. A negative blood smear makes the diagnosis of malaria unlikely; however, because non-immune individuals may be symptomatic at very low parasite densities that initially may be undetectable by blood smear, blood smears should be repeated every 12 to 24 hours for a total of three sets. If all three are negative, the diagnosis of malaria has been essentially ruled out.20

After malaria parasites are detected on a blood smear, the parasite density should then be estimated. The parasite density can be estimated by looking at a monolayer of red blood cells (RBCs) on the thin smear using the oil immersion objective at 100x. The slide should be examined where the RBCs are more or less touching (approximately 400 RBCs per field). The parasite density can then be estimated from the percentage of infected RBCs.20

In addition to microscopy, other laboratory diagnostic tests are available. Several antigen detection tests (rapid diagnostic tests or RDTs) using a “dipstick” or cassette format exist, but only one is approved for general diagnostic use in the United States. RDTs can more rapidly determine that the patient is infected with malaria, but they cannot confirm the species or the parasitemia. Parasite nucleic-acid detection using polymerase chain reaction (PCR) is more sensitive and specific than microscopy but can be performed only in reference laboratories and should be reserved for specific instances (e.g., back-up or confirmation of microscopy). Serologic tests, also performed in reference laboratories, can be used to assess past malaria experience but not current infection by malaria parasites. State health departments or the CDC can be contacted for more information on utilizing one of these tests.20

Determination of the infecting Plasmodium species for treatment purposes is important for three main reasons:

  • Plasmodium falciparum and Plasmodium knowlesi infections can cause rapidly progressive severe illness or death, while the other species — Plasmodium vivax, Plasmodium ovale, or Plasmodium malaria — are less likely to cause severe manifestations.20
  • P vivax and P ovale infections also require treatment for the hypnozoite forms that remain dormant in the liver and can cause a relapsing infection.20
  • P falciparum and P vivax species have different drug-resistance patterns in differing geographic regions. For P falciparum and P knowlesi infections, the urgent initiation of appropriate therapy is especially critical.20

Patients diagnosed with malaria are generally categorized as having one of two types of the virus: uncomplicated or severe. Only a specific blood test can confirm the diagnosis — and unfortunately, in some countries, such a test is not readily available.20 Patients who have one or more of the following clinical criteria (impaired consciousness/coma, severe normocytic anemia [hemoglobin <7], renal failure, acute respiratory-distress syndrome, hypotension, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria, jaundice, repeated generalized convulsions, and/or parasitemia of >5%) are considered to have manifestations of more severe disease.20

Symptoms of malaria are generally non-specific and most commonly consist of fever, malaise, weakness, gastrointestinal complaints (nausea, vomiting, diarrhea), neurologic complaints (dizziness, confusion, disorientation, coma), headache, back pain, myalgia, chills, and/or cough. The diagnosis of malaria should also be considered in any person with fever of unknown origin regardless of travel history.20

Malaria facts

In the world: Each year an estimated 190 million to 311 million cases of malaria occur worldwide, killing more than a million people — most of them young children in sub-Saharan Africa.20 More than 3.3 billion people live in 109 countries and territories at risk of malaria transmission.21

In the United States: On average, 1,500 cases of malaria are reported every year in the United States, even though malaria had been eradicated in the United States in the early 1950s.20 From 1963 to 2009, 96 cases of transfusion-transmitted malaria were reported in the U.S.; most of these cases could have been prevented if the affected donors had been deferred according to guidelines.20

In the news: According to new research tracking deforestation in Brazil's Amazon published in the June 16 issue of Emerging Infectious Diseases, relatively small changes to the forest can have major effects on the health of the local population. Scientists from the University of Wisconsin-Madison say the clearing of tropical forests increases malaria rates dramatically because it creates conditions that are favorable for the Anopheles darlingi mosquito, the primary malaria carrier in the Amazon. Their study revealed a 48% increase in malaria cases in one county in Brazil after 4.2% of its tree cover was cleared. The disease infected an estimated 500,000 Brazilians annually from 1997 to 2006.22

Treatment: Uncomplicated is effectively treated with oral antimalarials Severe disease should be treated aggressively with parenteral antimalarial therapy. If untreated or unsuccessfully treated, malaria can result in severe headaches, epileptic attacks, respiratory difficulties, kidney failure, loss of consciousness and then death.20 Resistance to the best antimalarial drugs likely will emerge; artemisinin resistance is occurring already in Southeast Asia, and there is great concern that it could spread more widely if not aggressively contained.21

Similarly, mosquitoes already have demonstrated the ability to develop resistance over time to the insecticides used to control their spread. A pipeline of new drugs and insecticides is required to keep up with the inevitable resistance to these interventions.21 In addition, different species and strains of malaria parasite infect different populations throughout the world. Widespread infection of humans in Malaysia with P knowlesi, a malaria species previously known to infect non-human primates, led to its identification as the fifth malaria species capable of infecting humans.21

Treatment of malaria depends on many factors including disease severity, the species of malaria parasite causing the infection, and the part of the world in which the infection was acquired. The latter two characteristics help determine the probability that the organism is resistant to certain antimalarial drugs. Additional factors such as age, weight, pregnancy status, and drug allergies or other medications taken by the patient may limit the available options for malaria treatment.20 Most drugs used in treatment are active against the parasite forms in the blood (the form that causes disease) and include:

  • chloroquine
  • atovaquone-proguanil (Malarone)
  • artemether-lumefantrine (Coartem)
  • mefloquine (Lariam)
  • quinine
  • quinidine
  • doxycycline (used in combination with quinine)
  • clindamycin (used in combination with quinine)
  • artesunate (not licensed for use in the United States but available through the CDC malaria hotline).20

In addition, primaquine is active against the dormant parasite liver forms (hypnozoites) and prevents relapses. Primaquine should not be taken by pregnant women or by people who are deficient in G6PD (glucose-6-phosphate dehydrogenase). Patients should not take primaquine until a screening test has excluded G6PD deficiency.20

A Phase III trial of the world's most clinically advanced malaria vaccine candidate was launched in Kisumu, Kenya, in July 2009 in 11 sites in seven African countries. The Phase III trial was designed to demonstrate how the vaccine performs in two groups of children — one aged 6 weeks to 12 weeks and a second aged 5 months to 17 months — in different transmission settings across a wide geographic region in Africa. (In Phase II testing, the vaccine reduced cases of malaria in young children 5 months to 17 months by 53%.) If proven effective, the vaccine will complement existing interventions, such as insecticide-treated bed nets, indoor residual spraying, and effective drug therapies, to help prevent death due to malaria. Malaria kills approximately 900,000 people a year worldwide, most of them children living in sub-Saharan Africa. The vaccine candidate — in development since the mid-1980s — was the first of the current generation of malaria vaccines to warrant Phase III testing on this scale, and was more than 50% effective in reducing episodes of clinical malaria in children 5 months to 17 months old in earlier testing The vaccine can be administered together with the package of vaccinations routinely given to African children. If Phase III results are as good, the vaccine could be fully available in the next five to 10 years.20

Key interventions to control malaria include prompt and effective treatment with artemisinin-based combination therapies; use of insecticidal nets by people at risk; and indoor residual spraying with insecticide to control the vector mosquitoes.23


20. Centers for Disease Control and Prevention. Malaria. February 8, 2010. http://www.cdc.gov/malaria/. Accessed July 12, 2010.

21. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Malaria. http://www.niaid.nih.gov/news/newsreleases/2009/Pages/malaria_proceedings.aspx. Accessed July 12, 2010.

22. Fox M. Cleared Forests Lead to Rise in Malaria in Brazil. ABC News. June 16, 2010. http://abcnews.go.com/Technology/wireStory?id=10933529. Accessed July 12, 2010.

23. Purlain T. Morocco certified malaria free. Vaccine News Daily. June 16, 2010. http://vaccinenewsdaily.com/news/213417-morocco-certified-malaria-free. Accessed July 12, 2010.