Severe Malaria — Nail It Before It Nails You

Source: Bruneel F, et al. The clinical spectrum of severe imported falciparum malaria in the intensive care unit. Am J Resp Crit Care Med 2003;167:684-689.

Infection with plasmodium falciparum is responsible for more than 5000 deaths every day, predominantly among African children. Yet with modern air transportation, severe malaria easily is transported worldwide during its two-week incubation period and can present in any American emergency department (ED). Up to 1300 cases of imported malaria are documented each year in the United States, an average of 25 per state. Physicians evaluating febrile, severely ill travelers must be vigilant for this potentially fatal infectious syndrome.

To better define the clinical spectrum of severe malaria, Bruneel and colleagues studied 188 adults admitted to a 1200-bed teaching hospital in Paris between 1988 and 1999. All had P. falciparum parasites in blood smears and were admitted to intensive care (ICU). Using World Health Organization criteria, 93 of the 188 patients were categorized as having "severe malaria" by the presence of one or more of the following features: 1) unarousable coma with Glasgow Coma Scale score less than 10; 2) hemoglobin less than 5 gm/dL; 3) acute renal failure; 4) pulmonary edema with ARDS; 5) hypoglycemia less than 40 mg/dL; 6) shock with systolic BP less than 80 mmHg; 7) disseminated intravascular coagulation; 8) seizures; 9) acidosis, with pH less than 7.25 or serum HCO3 less than 15 meq/L.

"Less severe malaria" occurred in 95 of 188 cases and was defined as ICU patients lacking these nine major criteria but with minor criteria, including having impaired consciousness (but arousable), prostration, fever greater than 40°C, jaundice, greater than 5% parasitemia, or high risk conditions. All 188 cases were treated with intravenous quinine and intensive monitoring, with titration of pCO2 to 35-40, elevated head of bed, normalization of glucose, sedation, and mannitol as appropriate.

Average age of cases was 38 years (14-74); 119 were male. Ninety-four percent of infections were acquired in sub-Saharan Africa (mainly Ivory Coast, Cameroon, Benin, Mali, Congo, Kenya, Zaire, and Gabon). Ninety-six percent took no or inappropriate malaria chemoprophylaxis. Of 93 severe cases, there were 10 fatalities (11%), all of whom took no malaria prophylaxis. Thirty required airlift to Paris for treatment. Average falciparum parasitemia was 4.1% overall vs. 18.2% among fatalities. Temperatures ranged from 39.5°C to 40.5°C. Mean time to malaria diagnosis was four days. The mean ICU stay was 7.5 days (4-13). Forty patients needed mechanical ventilation; 12/93 developed adult respiratory distress syndrome (ARDS). Shock occurred in 24. Fifty-four percent had acute renal failure, necessitating dialysis or continuous venovenous hemofiltration in 29. Fifty-one needed transfusion. Of 28 cases undergoing neuroimaging, three had deep white matter lesions, two had massive cerebral edema, two had ischemia, and one each had herniation, frontal hematoma, and meningeal enhancement. Pneumonia and bacteremia were documented in 14% of cases. Four criteria were associated with mortality: unarousable coma, ARDS, shock, and acidosis (p < 0.001 for all four). Among the less severe cases, 94% took inadequate chemoprophylaxis. The mean ICU stay was two days (1-4). There were no deaths among this group.

Commentary by Michael Felz, MD

The authors, and an accompanying editorial, state that this is the largest study ever published of severe imported malaria in a single center. We must, therefore, take heed of these findings. As a medical missionary to Papua New Guinea, I witnessed firsthand the ravages of severe malaria among villagers and expatriates. Bruneel and colleagues’ description of the clinical spectrum of severe falciparum malaria is equally vivid to me and provides useful parameters for early diagnosis by ED physicians seeing ill travelers in the United States. The history of recent (< two weeks) sub-Saharan itineraries, so apparent in this study, serves as a persuasive clue for early detection. The four predictors of ICU mortality must be recognized and managed just as aggressively as the parasitemia itself. A 20% overall rate of concomitant bacterial infection warrants broad spectrum antibiotic coverage, as well.

Most glaring of all is the abject lack of adherence to strongly recommended, easily available chemoprophylaxis medications. Over 90% of these infected travelers took no, or inadequate, preventive regimens during exposure in highly endemic African nations. Why so neglectful? What motivation is required? The factors are many, but the message is clear. Falciparum malaria is a killer. Any febrile traveler (to endemic regions) has malaria until proven otherwise. And an ounce of (chemo) prevention is worth pounds of (ICU) cure.

Dr. Felz, Associate Professor, Department of Family Medicine, Medical College of Georgia, Augusta, GA, is on the Editorial Board of Emergency Medicine Alert.