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Key Points

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  • Disease summary:

    • Malaria is a major parasitic infection in humans with significant global health impact. The pathogen Plasmodium completes its sexual maturation in mosquitoes, which in turn transmit sporozoites to humans while feeding on their blood. In humans, the liver incubates sporozoites allowing for their asexual reproduction before their release into the blood stream where they continue their reproduction in red blood cells (RBCs), altering their properties, and causing the various symptoms of malaria.

  • Differential diagnosis:

    • Consider viral infections such as HIV seroconversion, dengue fever, hepatitis A, B, and E, influenza and viral hemorrhagic fevers. Bacterial infections with a similar presentation include typhoid, pneumonias, and leptospirosis.

  • Monogenic forms:

    • Genetic host and pathogen factors are known to influence the disease risk. The best known host genetic factor is sickle cell hemoglobinopathy where carriers of this disease have an approximately 10-fold increase in protection against severe and complicated malaria.

  • Genome-wide associations:

    • A number of genetic variants in the pathogen genome have been identified, some of which may serve as candidates for the development of more effective antimalarial therapies and vaccines.

  • Pharmacogenomics:

    • Some antimalarial drugs can cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency so measurement of G6PD activity is indicated.

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Diagnostic Criteria and Clinical Characteristics

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Clinical Characteristics

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Malaria should be suspected in anyone who has previously visited a malaria-endemic area, including those that took prophylaxis. Human malaria can be caused by five species of Plasmodium (Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and the simian parasite Plasmodium knowlesi) out of which infections by P falciparum and P vivax are most common. Human infection with P knowlesi is thought to be a zoonosis and has only been reported in Southeast Asia.

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Signs and Symptoms
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  • Incubation period can be as short as 6 days for naturally acquired infection. Most patients who have a P falciparum infection will present within 6 months of exposure. P vivax and P ovale may enter a hypnozoite stage in the liver with infections usually presenting more than 6 months, and occasionally years, after exposure. There is a risk of relapse if only the blood phase of the disease is treated and the hypnozoites are not cleared.

  • Symptoms are nonspecific and there are no pathognomonic features. Most patients complain of fever or sweats or rigors, myalgia, headache, and general malaise. Malaria may be misdiagnosed as influenza or another respiratory viral infection, or as gastroenteritis due to gastrointestinal symptoms and jaundice. The fever typically does not follow the classically described quotidian, tertian, or quartan patterns.

  • Signs are also nonspecific and reminiscent of many other conditions. A fever is not invariably present and hepatomegaly is uncommon in acute malaria. Children are more likely to have hepatosplenomegaly than adults.

  • Severe or complicated falciparum malaria may present with

    • Metabolic acidosis (pH <7.35)

    • Hypoglycemia (blood glucose <2.2 mmol/L)

    • Shock

    • Anemia (Hb <8 g/dL)

    • Disseminated intravascular ...

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