Reducing Deaths From Malaria

Abstract and Commentary

Synopsis: Death occurred in about 1 per 100 cases of malaria diagnosed in U.S. travelers from 1963 to 2001, and many factors contribute to death from malaria. Most were preventable, and people returning home to visit friends and relatives have now become the leading risk group for malaria-related deaths.

Source: Newman RD, et al. Malaria-Related Deaths Among U.S. Travelers, 1963-2001. Ann Intern Med. 2004;141: 547-555.

Newman and colleagues reviewed fatal cases of malaria that occurred from 1963 to 2001 in U.S. travelers that were reported to the National Malaria Surveillance System. Among the 185 reported cases of malaria-related deaths, 123 (66.5%) occurred in U.S. travelers, while the rest occurred in refugees, visitors, military personnel, and others. Among the U.S. travelers, there was a male predominance (60%). The majority of deaths (92.7%) were associated with 1 species, Plasmodium falciparum, whereas deaths due to other species occurred occasionally: P. vivax 3.3%, P. malariae 1.6%, and P. ovale 0.8%. The level of parasitemia with P. falciparum ranged from 1-60%, with a mean of level of 21.4%.

The overall case-fatality rate for U.S. travelers was 0.9%. When analyzed by species from 1985 to 2001, the case-fatality rates were: 3% for P. falciparum, 0.06% for P. vivax, 0.3% for P. malariae, and 0.3% for P. ovale. The majority of fatal cases were acquired in Africa, and were led by infections acquired in Kenya, Nigeria, and Liberia, with stays of < 1 day to 23 years; median 22 days. The main reason for travel was reported to be tourism (17.9%), followed closely by business (16.3%), missionary activities (13.8%), and visiting friends and relatives (VFR, 11.4%). However, the reasons for travel have changed in more recent years (1989-2001), with visiting friends and relatives (VFR) as the leading reason for travel (21.3%), followed by business (19.2%), missionary work (10.6%), and tourism (8.5%).

Only 7 of 123 (5.7%) persons were found to have taken proper malaria chemoprophylaxis and adhered to the regimen. Forty-six percent of the cases used no prophylaxis, 35.3% used an inappropriate drug, 4.9% were noncompliant, and data were unknown in 26%.

Clinical symptoms included fever (77.2%), chills (45.9%), mental status changes (19.7%), myalgia (18.9%), fatigue or malaise (18.0%), diarrhea, weakness, vomiting, headache, nausea, nonspecific respiratory symptoms, lethargy, cough, abdominal pain, jaundice, sweats, dizziness, anorexia, and seizures. Notably, 18.7% did not have a history of fever or chills. Onset ranged from 18 days before return to 4 years after return, with a median of 5 days following return. A case of P. ovale occurred 4 years after return, and a case of P. malariae occurred some unknown years after travel to China.

Complications included cerebral malaria (48%), renal failure (43.9%), acute respiratory distress syndrome (ARDS, 31.7%), anemia (21.1%), and disseminated intravascular coagulation (DIC, 11.4%). Splenic rupture caused deaths in 4.9% of the cases, and occurred 3-15 days after symptom onset. Newman and colleagues considered 85.4% of the malaria deaths to be preventable; 79% of cases included patient decisions that contributed to death, but 66.7% of cases involved medical errors (see Table).

Comment by Lin H. Chen, MD

This thorough, thoughtful analysis examined many factors that contribute to malaria-related deaths among U.S. travelers, and found the vast majority of deaths to be preventable, in spite of a decrease in the case-fatality rate of falcipaum malaria from 3.8% from a 1966-1987 study.1 Newman et al have identified many delays and errors that contribute to the malaria deaths (see Table). Newman et al emphasized a number of improvements that are still necessary in order to reduce malaria-related deaths:

  • Health care providers must ask about past travel history, obtain malaria smears, and establish the diagnosis of malaria in a timely fashion.
  • Treatment with appropriate antimalarials must be initiated as soon as the diagnosis of malaria is made, and presumptive treatment for malaria should be started if blood smears cannot be read immediately.
  • All cases of confirmed, possible, or suspected P. falciparum must be treated as medical emergencies.
  • Hospitals must have intravenous quinidine gluconate on formulary sufficient for a 10mg/kg loading dose followed by 70 hours of continuous infusion at 0.02mg/kg/minute.

One complex issue remains. How can medical professionals influence patients to obtain pre-travel evaluation, to adhere to malaria chemoprophylaxis, and to seek medical care for illness after returning from travel? Wider publicity and education regarding malaria are needed. Travel medicine specialists possess the expertise to contribute significantly in these areas.

This study also illustrates the travel health risks for VFRs as shown previously.2 The trend towards VFRs as the leading group of travelers to die from malaria corroborates recent studies that have found VFRs to be the leading group of travelers who acquire malaria.3,4 In an analysis of malaria occurring in travelers in the GeoSentinel database, 85% of VFRs did not have a pre-travel encounter, and were less likely to take malaria chemoprophylaxis.4 Similarly, VFRs are the leading group of travelers to acquire typhoid fever during their overseas visits (Reviewed in Travel Medicine Advisor Update 2004;14(10):53-6).5 Education about malaria in immigrant communities may eventually lead to better acceptance of pre-travel evaluations, improved adherence to malaria chemoprophylaxis, and timely presentation for medical care of travel-related illnesses.

Resources

  • CDC 24-hour Malaria Hotline: 770-488-7788
  • CDC Malaria Web Site: www.cdc.gov/malaria
  • Eli Lilly (manufacturer of quinidine in the U.S.): 800-821-0538

References

1. Greenberg AE, et al. Mortality From Plasmodium falciparum Malaria in Travelers From the United States, 1959 to 1987. Ann Intern Med. 1990;113:326-327.

2. Bacaner N, et al. Travel Medicine Considerations For North American Immigrants Visiting Friends and Relatives. JAMA. 2004;291:2856-2864.

3. Schlagenhauf P, et al. Migrants As a Major Risk Group For Imported Malaria. J Travel Med. 2003;10:106-107.

4. Leder K, et al. Malaria in Travelers: A Review of the GeoSentinel Surveillance Network. Clin Infect Dis. 2004;

5. Steinberg EB, et al. Typhoid Fever in Travelers: Who Should Be Targeted For Prevention? Clin Infect Dis. 2004;39:186-191.

Lin H. Chen, MD, Assistant Clinical Professor, Harvard Medical School Director, Travel Resource Center, Mt. Auburn Hospital, Cambridge, Mass, is Associate Editor for Travel Medicine Advisor.