VAIL, COLO. – Fever in a traveler back from the tropics is malaria until proven otherwise – and it’s a medical emergency, Dr. Jay S. Keystone said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.
"Death from malaria can occur in 3-4 days. Not always, but it can. That’s all it takes," said Dr. Keystone, professor of medicine at the University of Toronto and a past president of the International Society of Travel Medicine.
If it’s malaria due to Plasmodium falciparum in a nonimmune patient – and children should be assumed to be nonimmune – hospital admission for up to 48 hours is warranted, even if only minimal parasitemia is present. There’s no need to keep the patient in the hospital until the parasitemia is zero; once the parasitemia is falling in response to therapy, monitoring can safely be accomplished on an outpatient basis with daily blood films until the patient has fully recovered.
CDC/Neva Gleason
Always assume that post-travel fever is malaria; death from the disease can occur quickly.
Why admit a patient with mere low-level P. falciparum parasitemia? Dr. Keystone has seen returned travelers with a several-day history of fever go from 1% to 30% parasitemia in the course of just 9 hours.
"You really don’t know the parasitemia mass when you’re looking at the blood film because most of the falciparum develops in the microcirculation," he explained.
The one exception to his maximum 48-hour hospitalization rule is in patients with a heavy P. falciparum infection as defined by 5% or greater parasitemia. Onset of adult respiratory distress syndrome in such patients often occurs on day 3-4 of treatment, just as they’re starting to look markedly better and their parasitemia is coming down.
The clinical hallmark of malaria is fever. "That’s the only thing you have to know about what malaria looks like. And if there’s no periodicity to the fever, ignore that; malaria is still in the differential diagnosis," Dr. Keystone said. "For falciparum, the fever you’re most worried about, there really is only rarely periodicity, especially in children. If, however, there is an exact periodicity – fever every other day, every third day, et cetera – it can only be malaria."
In a study Dr. Keystone coauthored that provided the first systematic evaluation of illness in returned pediatric travelers, febrile illness was the presenting complaint in 23% of 1,591 ill children seen at 51 tropical medicine clinics in the GeoSentinel Global Surveillance Network maintained by the International Society of Travel Medicine and U.S. Centers for Disease Control and Prevention. In fact, fever was the third most common presenting complaint, after diarrhea in 28% of patients and dermatologic conditions in 25%.
Of 358 ill returned pediatric travelers with fever, malaria was the No. 1 cause, accounting for 35% of cases, followed by upper respiratory tract infections and other viral illnesses in 28% (Pediatrics 2010;125: 1072-80).
The diagnosis of malaria is made based upon thick blood films; speciation is based upon thin films. If the first blood film is negative, testing should be repeated daily for 2 additional days; otherwise, it’s quite possible to miss parasitemia.
As an alternative to the time-honored thick blood films, Dr. Keystone strongly recommended the use of rapid diagnostic tests, in which malaria is diagnosed based upon detection of malaria antigen in the blood. These tests have been shown to have 99% sensitivity and 94% specificity for P. falciparum infection, and 94% sensitivity and 100% specificity for Plasmodium vivax.
"In Ontario, that’s all we do – we do the rapid diagnostic test, then thin blood films looking for the species and the parasitemia. Rapid diagnostic tests are especially good if your lab doesn’t have a lot of experience with malaria, as you’d expect in a place such as Colorado," he noted.
Parasitemia of 1% or greater is due to P. falciparum more than 90% of the time. In parasitemia, 5% is a critical number; at that level, parenteral therapy is warranted and there is a risk of death.
"At 10% or more, it’s time to change your underwear," Dr. Keystone quipped. "You’ve got a serious problem. At that point, you’re always thinking about exchange transfusion."
Recognizing and Treating Malaria in the United States
Who brings malaria back to the United States from abroad? A recent CDC analysis of cases imported during 2009 concluded that U.S. immigrants who had been visiting friends and relatives abroad accounted for 63% of cases. Missionaries made up another 10%, with the remainder being divided between tourists, business travelers, and students (MMWR Surveill. Summ. 2011 Apr;60:1-15).