Malaria Diagnosis and Treatment

Malaria is a serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and…. “flu-like” illness. Although malaria can be a deadly disease, illness and death from malaria can usually be prevented.

About 1,700 cases of malaria are diagnosed in the United States each year. The vast majority of cases in the United States are in travelers and immigrants returning from countries where malaria transmission occurs, many from sub-Saharan Africa and South Asia.

Malaria is transmitted to humans via the bite of an infected female Anopheles mosquito. Plasmodium sporozoites are injected into the host’s bloodstream during the mosquito’s blood meal and are carried through the bloodstream to the liver. Within the liver, the parasite multiplies into thousands of daughter merozoites by asexual reproduction. Some Plasmodium species (vivax and ovale) can remain dormant as hypnozoites within the hepatic cell for years resulting in latent disease. Eventually, the hepatic cell ruptures and the merozoites are released in the blood stream.

Once in the bloodstream, the merozoites invade erythrocytes, feeding on hemoglobin, lysing the red blood cell, and then moving on to the next red blood cell.

Most of the pathology caused by Plasmodium is due to the sequestration of red blood cells in various organs, causing ischemia or organ dysfunction due to heme accumulation. Furthermore, the lysis of both hepatocytes and erythrocytes has direct effects on the liver and blood counts, causing jaundice and anemia. Other organs frequently affected include the brain, lungs, and kidneys. Brain pathology is linked to the accumulation of adherent reticulocytes in the brain venules, impairing blood circulation.

Malaria must be considered in any patient with a history of fever and travel to an endemic region. Where malaria is found depends mainly on climatic factors such as temperature, humidity, and rainfall. Malaria is transmitted in tropical and subtropical areas, where:

• Anopheles mosquitoes can survive and multiply
• Malaria parasites can complete their growth cycle in the mosquitoes

Despite fever being a frequent presenting chief complaint, it should be noted that up to 35% of malaria cases  present with the absence of pyrexia. Over 80% are found to be tachycardic. Almost 50% will have abdominal tenderness, some 20% to 30% will have an enlarged liver and/or spleen, and nearly 10% will be jaundiced.¹

Uncomplicated Malaria: The clinical hallmark of malaria is fever, with a prodrome of malaise, myalgia, headache, and chills. Early symptoms are nonspecific and can easily be confused with a viral syndrome such as influenza or hepatitis or with bacterial sepsis.

Complicated Malaria: Malaria is described as severe or complicated when it includes one or more of the following syndromes: coma with or without seizures (“cerebral malaria”), prostration, severe anemia, acidosis, hypoglycemia, acute renal failure, acute respiratory distress syndrome, pulmonary edema, jaundice, intravascular hemolysis, shock, and disseminated intravascular coagulation. The common culprit in complicated malaria is Plasmodium falciparum. Case fatality rates range from 5% to 30% in patients that receive treatment for severe malaria.¹

The diagnosis of malaria rests on a history of potential exposure in an endemic malaria area, clinical signs and symptoms, and competent microscopic examination of thick and thin blood films.

The three major questions to be answered by the blood smear are as follows: (1) Is there evidence of malaria? (2) If so, what is the density of parasitemia (this correlates with prognosis)? (3) What species of malaria is responsible for the infection and, in particular, is P. falciparum present?

In the United States, there is only one FDA-approved rapid diagnostic test for malaria, called BinaxNOW® Malaria.

Treatment decisions are based on the severity of the illness and the species of the infecting parasite determined by microscopic examination of thick and thin blood films.

In cases of uncomplicated malaria, the primary goal of treatment is halting progression to severe or complicated infection. In cases of severe malaria infection, the goals of treatment are the prevention of immediate mortality and the preservation of neurologic function associated with cerebral malaria. Additionally airway protection, fluid resuscitation, antiepileptics, antipyretics, and management of anemia and hypoglycemia should be considered in patients with severe malaria.

Recommended treatments generally follow these guidelines:

• Uncomplicated chloroquine-sensitive (Central America and Caribbean) – Chloroquine phosphate
• Uncomplicated chloroquine-resistant areas (South America, South Asia, Africa) – Quinine (PO) + doxycycline OR atoavaquon/proguanil OR Mefloquine
• Complicated or Plasmodium falciparum – Quinidine (IV) AND doxycycline (IV) or Tetracycline or Clindamycin

Treatment guidelines are constantly changing based on resistance trends. The latest guidlines can be found at https://www.cdc.gov/malaria/diagnosis_treatment/treatment.html.

Patients who are generally well appearing and have access to anti-malaria medication can be discharged and follow-up with Infectious Disease as an outpatient.

Patients with suspected or confirmed Plasmodium falciparum or Plasmodium knowlesi, children, pregnant women, and immunodeficient individuals with malaria should be admitted. Consult Infectious Disease to follow the degree of parasitemia and response to treatment with serial blood smears.

ICU admission should be considered if there is evidence of end organ failure, coagulopathy, persistent hypoglycemia, or cerebral involvement (i.e. coma or seizures).