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Plasmodium Species Jaundice, Renal Failure, and Fatal Outcomes Similar to Severe P APPENDIX 2 Plasmodium Species jaundice, renal failure, and fatal outcomes similar to severe P. falciparum malaria. Humans acquire Disease Agent: monkey malarias when they share the same habitat. In Asia (Malaysia), four fatalities initially mistaken for • Plasmodium falciparum, P.vivax, P.malariae, P.ovale, P.malariae infections were subsequently attributed to P.knowlesi P.knowlesi; all were hyperparasitemic and developed Disease Agent Characteristics: marked hepatorenal dysfunction. P. knowlesi was detected by PCR in 266 (27.7%) of 960 archived • Protozoan, 2-4 mm (ring form) samples from patients with malaria in Malaysia and • Order: Haemosporida Malaysian Borneo. • Family: Plasmodiidae • All are intraerythrocytic parasites with characteristic Common Human Exposure Routes: microscopic appearance, some with portion of life • Bite of an infected female anophelene mosquito cycle in hepatic cells. • Life cycle includes asexual and sexual stages. Likelihood of Secondary Transmission: Disease Name: •Low • Transmitted transplacentally, by parenteral inocula- • Malaria tion including blood transfusion and organ Priority Level: transplantation At-Risk Populations: • Scientific/Epidemiologic evidence regarding blood safety: Low in most nonendemic countries but high in • Individuals at increased risk for exposure to infected hyperendemic countries. Risk and concern with mosquitoes because of travel to or residence in areas regard to blood safety may be moderate to high in where Plasmodium species are endemic some nonendemic countries, based on donor demo- Vector and Reservoir Involved: graphics and travel patterns of the donor population. • Public perception and/or regulatory concern regard- • Female mosquitoes of the genus Anopheles ing blood safety: Moderate; risk and concern with Blood Phase: regard to blood safety may be moderate to high in some nonendemic countries, based on donor demo- • Symptomatic patients: weeks to months before spon- graphics and travel patterns of the donor population. taneous clearance unless appropriately treated with • Public concern regarding disease agent: Moderate antimalarial drugs • Asymptomatic patients: persistence with periodic Background: blood phase in semi-immune individuals for years • Generally limited to tropical and subtropical regions (e.g., from 1 to greater than 50 years, depending on where it remains stable despite continued efforts to the species of malaria) eradicate the mosquito vector. Local epidemiology Survival/Persistence in Blood Products: can change rapidly in response to local geophysical and sociological conditions. • Generally, 7-10 days, based on historic data, but infor- • Remains major public health concern in endemic mation on RBCs stored in contemporary anticoagu- regions of the world, particularly for children less lants is not available than 5 years of age Transmission by Blood Transfusion: • Re-emergent in nonendemic areas because of immi- gration and travel • Multiple cases worldwide • Sporadic cases attributed to “airport malaria” and ᭺ Common in endemic countries autochthonous transmission increasingly reported ᭺ Only three cases in the US from 1998 through • Role of global warming heavily debated 2007 • Classically, there have been four Plasmodium species ᭺ Overall, US case rate has dramatically decreased associated with human malaria. Recently, a fifth during the last 40 years. Plasmodium species that causes human malaria has • The large majority of transmissions are from RBCs, been identified. Plasmodium knowlesi, whose natural but platelet components have been implicated, prob- hosts are forest-dwelling macaques (the long-tailed ably because of presence of RBCs. and pig-tailed macaque), has a rapid doubling time • Four of five species of Plasmodium transmitted, but a (once daily) and rapidly reaches high parasitemia large majority of recent US cases have been a result of levels in humans with rapid development of anemia, P.falciparum and, to a lesser extent, P.vivax. 224S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 Cases/Frequency in Population: ᭺ In cases with high parasitemia, exchange trans- fusion is recommended. • In the US, approximately 1000-1500 cases of malaria are reported yearly; 75% attributable to P.falciparum Agent-Specific Screening Question(s): and P.vivax infections. • Plasmodium species infections are primarily found in • Risk questions pertaining to residence in or travel to tropical and subtropical regions, where current esti- endemic areas or history of malaria are currently used mates suggest there are more than 500 million clinical in the US. cases of malaria and two million or more deaths Laboratory Test(s) Available: annually. The frequency varies considerably by loca- tion, with highest rates in sub-Saharan Africa. • No FDA-licensed blood donor screening test exists. Incubation Period: Two testing strategies have been discussed— universal screening to allow consideration of modify- • Varies by infecting species, immune status of patient ing the current donor geographic-risk questions and and number of parasites transmitted. For P. falci- the “testing-in” strategy for deferred donors. In the parum and P.vivax, incubation period may be 1 week US, both strategies appear to be dependent on test to 1 month but may require several months for P. kits containing antigens to the four main Plasmodium malariae. species infecting humans. Likelihood of Clinical Disease: • IFA and EIA to detect IgG antibodies are used for “testing in” (i.e., shortened deferrals) by several Euro- • Low/moderate in semi-immune residents of endemic pean countries and in Australia (i.e., donors with a areas, higher in nonimmune visitors. travel history that would otherwise lead to deferral are evaluated further by laboratory testing and allowed to Primary Disease Symptoms: donate sooner if their antibody test is negative; in • Periodic fever and rigors, chills, headache, myalgias, Australia, plasma, but not RBCs from seropositive arthralgias, splenomegaly, and hemolytic anemia donors can be used during the deferral period). • In blood recipients, onset of symptoms may be • Options for laboratory testing include blood smear delayed by months. The nonspecific nature of the microscopy, IFA, EIA, antigen based rapid diagnostic symptoms, plus their delay in onset, makes recogni- tests, and NAT. tion of clinical disease in blood recipients difficult. Currently Recommended Donor Deferral Period: Severity of Clinical Disease: • 1 year for travel to endemic areas • Most severe forms of malaria are associated with P. • 3 years for those who have lived for 5 or more years in falciparum. High levels of parasitemia observed, endemic areas leading to microvascular obstruction and severe com- • 3 years for those who previously had malaria and are plications (e.g., cerebral malaria). now asymptomatic Mortality: Impact on Blood Availability: • 1.5-2.7 million deaths per year worldwide • 11% of US transfusion cases are fatal, compared with • Agent-specific screening question(s): Current ques- 0.43% of vector-derived cases in the US tions result in the deferral of greater than 100,000 blood donors each year in the US, with very few likely Chronic Carriage: infected or infectious. ᭺ • Occurs classically for infections with P.malariae, less The impact of self-deferrals is unknown but likely commonly with P. ovale and P. vivax. Chronic infec- much greater. tions can also occur with P.falciparum, but are even • Laboratory test(s) available: Not applicable less common. Impact on Blood Safety: Treatment Available/Efficacious • Agent-specific screening questions(s): Transfusion- • Variety of drug treatments available worldwide transmitted cases continue to decline, with only three (not all in the US): chloroquine, sulfadoxine- cases since 1998, suggesting that current geographic pyrimethamine, mefloquine, atovaquone-proguanil, risk-factor questions are having a positive impact on quinine, doxycycline, and artemisinin derivatives blood safety; however, the impact of questions has ᭺ Widespread drug resistance has developed in not been evaluated empirically. many locations. • Laboratory test(s) available: Not applicable Volume 49, August 2009 Supplement TRANSFUSION 225S APPENDIX 2 Leukoreduction Efficacy: 5. Kitchen AD, Lowe PH, Lalloo K, Chiodini PL. Evalua- tion of a malarial antibody assay for use in the screen- • Unlikely to be effective for this intraerythrocytic ing of blood and tissue products for clinical use. Vox parasite Sang 2004;87:150-5. 6. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray Pathogen Reduction Efficacy for Plasma Derivatives: CJL. Global and regional burden of disease and risk factors, 2001; systematic analysis of population • No specific data are available but it is presumed that health data. Lancet 2006;367:1747-57. the agent should be sensitive to many measures used 7. Mungai M, Tegtmeier G, Chamberland M, Parise M. in the fractionation process. Transfusion-transmitted malaria in the United States from 1963 through 1999. N Engl J Med 2001;344: Other Prevention Measures: 1973-8. 8. Phillips P, Nantel S, Benny WB. Exchange transfusion • Mosquito avoidance as an adjunct to the treatment of severe falciparum • Antimalarial prophylaxis for visitors to endemic areas malaria: case report and review. Rev Infect Dis 1990; • Feasibility of pathogen reduction demonstrated using 12:1100-8. several different compounds and approaches 9. Seed CR, Kitchen A, Davis TM. The current status and potential role of laboratory testing to prevent Suggested Reading: transfusion-transmitted
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