Transfusion Malaria: Serologic Identification of Infected Donors -- Pennsylvania, Georgia

In 1982, CDC tested 122 sera from donors associated with the nine cases of transfusion malaria reported to CDC in 1982. (Nine is the highest annual number reported in the past 25 years; the same number was reported in 1971). The following cases illustrate the role of serologic testing in identifying donors infected with malaria.

Case 1, Pennsylvania: A 29-year-old woman received 18 units of red blood cells and 10 units of platelets after an automobile accident on March 16, 1982. On May 7, 52 days post-accident, she developed chills and fever. Plasmodium malariae was diagnosed on a peripheral blood smear. The patient was treated successfully with chloroquine.

Records of all donors were reviewed and showed no travel out of the continental United States for the preceding 3 years. One donor, a student of Liberian origin, had been in the United States since 1978. Serum samples were obtained promptly from 26 of the 28 donors and forwarded to CDC; samples from two persons could not be obtained. The Liberian donor had a malaria indirect fluorescent antibody (IFA) titer of 1:1024 to P. malariae, 1:256 to both P. falciparum and P. ovale, and 1:64 to P. vivax. No parasites were detected in the donor's blood; he was treated with chloroquine. Serum specimens from the remaining donors were negative by IFA testing.

Case 2, Georgia: On August 15, 1982, a 63-year-old retired serviceman received 26 units of blood and 15 units of platelets during and shortly after emergency repair of a ruptured abdominal aortic aneurysm. Nineteen days later, he began having episodes of fever and nausea. An infected aortic graft was suspected, and plans were made for an exploratory laparotomy. Before surgery, however, malaria parasites were detected on routine examination of a peripheral blood smear. The patient had served in Korea in 1950, 1953, and 1955; he took antimalarial drug prophylaxis intermittently during that time and had no history of malaria. At CDC, P. ovale was identified in the patient's blood, and his serum had an IFA titer of 1:1024 to P. ovale (titers were 1:64 to P. malariae and less than 1:16 to both P. falciparum and P. vivax). The patient was treated successfully with chloroquine.

Blood samples (unit segments) from 39 donors had been kept in the blood bank at the hospital where surgery was performed and were sent immediately to CDC; specimens from two donors were unavailable. Serum from four of the 39 donors had greatest IFA titers of 1:64 to P. ovale. Three of these four donors had not traveled to an area where P. ovale is transmitted. The fourth donor had served in the Peace Corps in Sierra Leone from 1977 to 1979, during which time he took chloroquine as antimalarial chemoprophylaxis. He had not taken primaquine to prevent relapses, nor had he experienced febrile illness compatible with malaria since leaving Africa. Serum tested several weeks later showed a titer of 1:256 to P. ovale, suggesting a recent parasitemia. Malaria parasites could not be detected on multiple examinations of thick blood smears. He was treated with chloroquine and primaquine to prevent further relapses of parasitemia. Reported by Lt Col B Johnson, Major JH Brown, Major R Yoedino, Martin Army Hospital, Fort Benning, RK Sikes, DVM, State Epidemiologist, Georgia State Dept of Human Resources; J Santoro, MD, Bala Cynwyd, M Dahlke, MD, American Red Cross Blood Svcs, Penn-Jersey Region, Philadelphia, CW Hays, MD, State Epidemiologist, Pennsylvania State Dept of Health; Malaria Br, Div of Parasitic Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Transfusion malaria occurs very infrequently in the United States. Between 1958 and 1976, the annual rate of transfusion-related cases was between 0 and 4.9 cases per million persons transfused (1), and has remained within this range through 1982. Estimates based on the number of units of blood collected in the United States since 1972 indicate that 0.25 cases of transfusion malaria have occurred per million units collected (2).

Because parasite density in an infected donor may be very low, there may be no clinical history of recent febrile illness or elevated temperature when blood is donated, and an infected individual may slip through the donor screening process. These two cases demonstrate that a thick blood film examination may also be a very insensitive screening procedure (3).

To protect recipients of red-blood-cell-containing products from inadvertently acquiring malaria, the American Association of Blood Banks (AABB) has set the following standards for donors who have traveled to or lived in endemic areas (4).

1. Travelers may donate blood 6 months after returning from

endemic areas if they have been free of symptoms and have not taken antimalarial drugs.

2. Persons who have had malaria or who had been taking chemoprophylaxis shall be deferred from donating blood for 3 years after either becoming asymptomatic or stopping therapy or chemoprophylaxis.

3. Immigrants or visitors from endemic areas may be accepted as donors 3 years after departure if they are asymptomatic in the interim.

4. Donations to be used in preparing plasma, plasma components, or derivatives devoid of intact red blood cells are exempted from these restrictions.

Proven carriers of malaria or persons who had malaria caused by P. malariae are excluded permanently from donating blood.

The 3-year limit has been established because infections with the relapsing forms of malaria (P. vivax and P. ovale) rarely persist more than 3 years after a naturally-acquired infection; non-relapsing malaria due to P. falciparum will generally present clinically within 3 months of the initial infection, but a semi-immune person may have an asymptomatic infection for a year or more. However, despite the AABB standards, some cases of transfusion malaria will continue to occur, because P. malariae (the most common cause of transfusion malaria, now considered a non-relapsing parasite) may remain undetected in the blood for many years. This was illustrated by case

1. Persons who might otherwise be excluded can slip through the screening process; the donor in case 2 left Sierra Leone less than 3 years before giving blood; apparently, this information was not noted at the time of donation.

Thus, it is important to maintain vigilance in screening blood donors, promptly diagnose suspected transfusion cases, and rapidly identify and treat the donor responsible for the infection. Because an IFA response is usually associated with current or prior malaria infection, serologic testing is a useful adjunct to the travel or exposure histories in identifying donors potentially responsible for transfusion-related malaria.

In 1982, to provide a more rapid and efficient response for malaria reference diagnosis, CDC reviewed the indications for which malaria IFA serologic testing is appropriate. The review noted that a diagnosis of acute malaria is best made by a properly collected, stained, and examined blood smear. Therefore, the major criteria for reference diagnostic serologic testing for malaria antibodies at CDC are: 1) identification of a donor for each transfusion-related case, and 2) assistance in diagnosing clinically suspected malaria in a patient for whom repeated blood smears have been negative. In addition, CDC can assist other laboratories in standardizing test reagents and procedures for malaria serology.

References

1. Lopez CE, Shultz MG. Incidence of transfusion malaria and standards for blood donor selection (letter). J Infect Dis 1977;135(5):875-6.

2. Guerrero IC, Weniger BG, Schultz MG. Transfusion malaria in the United States, 1972-1981. Ann Intern Med (in press).

3. Miller LH. Transfusion malaria. In: Greenwalt TJ, Jamieson GA, eds. Transmissible disease and blood transfusion. New York: Grune & Stratton 1975:241-66.

4. American Association of Blood Banks. Standards for blood banks and transfusion services. 10th ed. Washington, D.C.: American Association of Blood Banks, 1981.

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