Plasmodium species found in patient PH-2. (Image not from this patient.)
A 49-year-old man from Pennsylvania receives 4 units of packed red blood cells (PRBCs) on January 15 while undergoing hip replacement surgery. He is again hospitalized on February 1 with fever, hypotension, and renal failure. Peripheral blood smears show malaria infection. The patient has never traveled outside the United States.
The parasite species is shown in the figure to the right.
Question 1: What is the species?
The patient is treated with intravenous quinidine and doxycycline.
Question 2: Among the modes of infection below, which one is the most likely?
Infection during travel overseas
Infection by local Anopheles mosquito
The dates of onset of symptoms, between July 12 and September 14, are shown in the epi curve.
Question 3: What are the next steps of this epidemiologic investigation to determine the mode of transmission?
Conduct a donor traceback investigation of the PRBCs used for the patient’s transfusions
Canvass community for additional cases (and possible index case)
Confirm presence of Anopheles mosquitoes where the patient lives
Stored serum samples from all donors are tested. One donor has elevated IFA titers (1:16,384 to P. falciparum, 1:16,384 to P. malariae, 1:1024 to P. ovale, and 1:256 to P. vivax) indicating previous malaria infection. Though microscopy is negative, PCR performed on a stored sample from this same donor from the time of donation detects P. falciparum, indicating active infection. This donor was born in West Africa, had lived in Europe, and then returned to West Africa, where he had lived for approximately 20 years before immigrating to the United States 2 years ago.
Donors who have been implicated as infection sources in transfusion-transmitted malaria cases often have had undetectable levels of parasitemia; therefore, antibody detection has been the method of choice to identify infected donors in CDC investigations of transfusion-transmitted malaria cases. Malaria antibody testing is 95% sensitive and 99% specific. Because the donor emigrated from an area with endemic malaria, the positive predictive value for this test is high.
No available laboratory test is suitable for screening donated blood for malaria. Such a test would require 1) large-scale use design, 2) high sensitivity and specificity, and 3) ability to detect all species of Plasmodium that affect humans. In the United States, prevention of transfusion-transmitted malaria largely depends on careful questioning of prospective donors to defer those at increased risk for malaria. The Food and Drug Administration (FDA) recommends deferring residents of malaria-endemic areas for 3 years after they emigrate from those areas and deferring persons who have had malaria for 3 years after they become asymptomatic; the American Association of Blood Banks has published standards consistent with FDA recommendations (Box).
Summary of guidelines of the Food and Drug Administration and American Association of Blood Banks for deferral of blood donors at increased risk for malaria
Defer blood donation for 1 year
- Travelers who are residents of nonmalarious areas who have been in a malarious area may be accepted as donors 1 year after their return to the nonmalarious area (irrespective of the use of chemoprophylaxis) if they have been free of malaria symptoms.
Defer blood donation for 3 years
- Immigrants or visitors from malarious areas may be accepted 3 years after departure from the area if they have been asymptomatic. Former residents of malarious areas who now live in the United States but who return to visit a malarious area may be accepted as donoros 3 years after their most recent visit.
- Persons who have had a diagnosis of malaria should be deferred for 3 years after becoming asymptomatic.
- Mungai M, Tegtmeier G, Chamberland M, Parise M. Transfusion-transmitted malaria in the United States from 1963 through 1999. N Engl J Med 2001:344:1973-8.
- Zoon K. Recommendations for deferral of donors for malaria risk: letter to all registered blood establishments. Washington, DC: Food and Drug Administration, 1994.
- American Association of Blood Banks. Standards for blood banks and transfusions services, 21st ed. Bethesda, Maryland: American Association of Blood Banks, 2002.
In this case, the donor from West Africa should have been deferred. The case described in this report underscores the importance of close cooperation between managers of blood collection centers and state and federal public health officials whenever transfusion-related illness occurs. Such cooperation can facilitate traceback investigations and ensure prompt care of both donors and recipients, helping to strengthen the screening process, making blood transfusion as safe as possible, and ensuring an adequate supply of a lifesaving resource.
Malaria should be considered as a differential diagnosis of the febrile patient who has received a blood transfusion.
No suitable laboratory test is available for screening donated blood for presence of malaria parasites. Thus prevention of transfusion-transmitted malaria depends on careful questioning of prospective donors to defer those at increase risk for malaria.
Close cooperation between managers of blood collection centers and state and federal public health officials is essential whenever transfusion-related illness occurs.
Selected references related to transfusion-transmitted malaria:
- Mungai M, Tegtmeier G, Chamberland M, Parise M. Transfusion-transmitted malaria in the United States from 1963 through 1999. N Engl J Med 2001; 344:1973–8.
- Probable transfusion-transmitted malaria– Houston, Texas, 2003. MMWR Morb Mortal Wkly Rep 2003; 52: 1075-6.