Treatment of Falciparum Malaria

The most important first step in the treatment of malaria is species identification through microscopy. The morphology of various malarial parasites show distinct characteristics, but given the low incidence of imported malaria in the United States, species identification can often be difficult for laboratory technicians. In addition, microscopy (especially using thin smears) can miss low levels of parasitemia. Rapid diagnostic tests have shown to be effective in endemic areas, but only for detection falciparum malaria, and have not yet been approved for use in the United States. Rapid tests for vivax, ovale, and malariae species are still under development. Parasite nucleic acid detection using PCR is available in reference laboratories, but the CDC only recommends using PCR to confirm a diagnosis by microscopy. If the species cannot be identified, or if there is strong clinical suspicion which cannot be confirmed through laboratory testing, treatment for falciparum malaria should be initiated immediately.

Just a quick note on P. vivax and P. ovale strains: These species of malaria have prolonged liver phases, during which the parasite lies dormant in forms referred to as “hypnozoites.” In order to eliminate these parasites in the liver, and to prevent future relapses, patients require treatment with chloroquine or quinine, plus a 14 day course of primaquine (“the radical cure” for malarial infection). One more note of caution: prior to administering primaquine, patients must be evaluated for G6PD deficiency, since it can cause hemolytic anemia. Consequently, primaquine is contraindicated in pregnancy because the G6PD status of the fetus cannot be determined. Primaquine should be added to treatment regimes for patients with falciparum malaria who are co-infected with vivax or ovale species.

It is also essential to determine the patient’s travel history, and to correlate this with regional patterns of resistance. Chloroquine resistance is widespread, and as such, chloroquine should only be used in the treatment of uncomplicated falciparum malaria for travelers returning from areas with chloroquine-sensitive strains (Central America west of Panama Canal, Haiti, the Dominican Republic, and most of the Middle East). Additionally, it’s important to ask patients about chemoprophylaxis. In case of resistance, providers should choose drug regimes that do not include medications that were used for prophylaxis (even intermittently).
It is recommended that patients with uncomplicated AND severe falciparum malaria be hospitalized. Given the rapid progression of disease, and the high mortality rates among cases of severe falciparum malaria, antimalarial treatment should be initiated urgently.

In general, patients with uncomplicated falciparum malaria can be treated with oral medication. For those patients who have returned from areas with chloroquine-sensitive strains, the dose, according to the CDC guidelines, is as follows:

Chloroquine phosphate (Aralen™ and generics): 600 mg PO immediately, followed by 300 mg PO at 6, 24, and 48 hours.

The CDC recommends four possible treatment plans for uncomplicated falciparum malaria acquired in regions with chloroquine-resistance (or when patients acquired malaria in a region where the sensitivity pattern is not known). Of the four treatment plans, two utilize medications which are commonly used for chemoprophylaxis (Atovaquone-proguanil or Malarone™, and Mefloquine or Lariam™). Therefore , these treatment protocols will not be appropriate for some patients. Additionally, Mefloquine when administered at treatment doses is associated with a high risk of severe neuropsychiatric reactions. A third protocol utilizes Quinine Sulfate, plus Doxycycline, Tetracycline, or Clindamycin (for children or women who are pregnant or breastfeeding). However, this treatment plan is associated with significant adverse effects, including Quinine-induced hypoglycemia, and gastrointestinal distress related to Doxycycline.

A treatment regime which includes artemesinin-combination therapy is recommended by WHO, and is one of the four regimes recommended by the CDC. In April 2009, the FDA approved Artemether and Lumefantrine (Coartem) as an oral therapy for the treatment of acute, uncomplicated malaria infections in adults and children weighing at least 5 kgs. The following treatment protocol is from the CDC:

Artemether-lumefantrine (Coartem™), 1 tablet = 20mg artemether and 120 mg lumefantrine

A 3-day treatment schedule with a total of 6 oral doses is recommended for both adult and pediatric patients based on weight. The patient should receive the initial dose, followed by the second dose 8 hours later, then 1 dose po bid for the following 2 days.

5 - <15 kg: 1 tablet per dose
15 - <25 kg: 2 tablets per dose
25 - <35 kg: 3 tablets per dose
≥35 kg: 4 tablets per dose

The most common adverse reactions reported in adults are headache, anorexia, dizziness, physical weakness, arthralgia and myalgia, although these are difficult to separate from the symptoms of malaria. The most common adverse reactions reported in children are fever, cough, vomiting, loss of appetite, and headache.
While some patients may tolerate Coartem better than other treatment regimes, Coartem may not be available in all areas of the United States. If there are no contraindications, patients should receive medications that are appropriate for their malarial species and sensitivity patterns, and which can be administered without delay.

For severe malaria, or in cases when oral medications cannot be used, parenteral quinine plus Doxycycline, Tetracycline, or Clindamycin should be used. Parenteral quinine is cardiotoxic and should only be administered in an ICU setting with continuous cardiac monitoring and frequent blood pressure monitoring. Regular blood glucose monitoring is also required. As another option, parenteral Artesunate is currently being considered as an investigational new drug (IND).

Supportive therapy for cases of severe malaria may include antipyretic meds, monitoring of fluid I&Os, hemodialysis in the case of renal impairment, supplemental oxygen or (in extreme cases) mechanical ventilation, transfusion, vitamin K for DIC, and diazepam for seizures. Exchange transfusion is recommended in cases of falciparum when parasitemia is greater than 10 percent, or in patients with coma, renal failure, or ARDS, regardless of the level of parasitemia.

The CDC website is a great resource, and they have a helpful treatment table to guide prescribing practice:

http://www.cdc.gov/malaria/pdf/treatmenttable.pdf