None too S.M.A.LL: the global challenge of severe malarial anaemia and its transfusion support
ISBT Education. Cserti-Gazdewich C.
Jun 3, 2018; 218839
Topic: Clinical practice
Christine Cserti-Gazdewich
Christine Cserti-Gazdewich
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Learning Objectives
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After viewing this presentation the participant will be able to:

- Quantify the scope of the problem of severe malarial anemia (SMA) in the world today
- Explain the pathogenesis of SMA
- Prescribe hemotherapy (most appropriate trigger and dose) for SMA
- List the limitations and risks of hemotherapy as it is currently structured in malaria-endemic areas
1 Kassebaum NJ, Collaborators GBDA: The Global Burden of Anemia. Hematol Oncol Clin North Am 2016; 30: 247-308.
2 Stevens GA, Finucane MM, De-Regil LM, et al.: Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995-2011: a systematic analysis of population-representative data. The Lancet Global health 2013; 1: e16-25.
3 Ashley EA, Pyae Phyo A, Woodrow CJ: Malaria. Lancet 2018; 391: 1608-21.
4 Poostchi M, Silamut K, Maude RJ, et al.: Image analysis and machine learning for detecting malaria. Transl Res 2018; 194: 36-55.
5 Gelabert P, Olalde I, de-Dios T, et al.: Malaria was a weak selective force in ancient Europeans. Sci Rep 2017; 7: 1377.
6 Kwiatkowski DP: How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet 2005; 77: 171-92.
7 Bhatt S, Weiss DJ, Cameron E, et al.: The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature 2015; 526: 207-11.
8 Vogel G: Fever dilemma. Science 2018; 359: 1090-2.
9 World Health Organization: World malaria report. Geneva, Switzerland, World Health Organization, 2016: p. 186.
10 Collaborators GBDCoD: Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390: 1151-210.
11 Collaborators GBDM: Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390: 1084-150.
12 Cowman AF, Healer J, Marapana D, et al.: Malaria: Biology and Disease. Cell 2016; 167: 610-24.
13 UN: World Population Prospects: The 2017 Revision 2017.
14 Rethinking the fight as surge of malaria deaths in conflict zones threatens to upend progress. EurekAlert! , American Association for the Advancement of Science (AAAS), 17-APR 2018. (Last accessed 27 June 2018).
15 Harari YN: Homo Deus : A Brief History of Tomorrow. ed First U.S. edition. New York, NY: Harper, an imprint of HarperCollins Publishers; 2017.
16 Pitman JP, Wilkinson R, Liu Y, et al.: Blood component use in a sub-Saharan African country: results of a 4-year evaluation of diagnoses associated with transfusion orders in Namibia. Transfus Med Rev 2015; 29: 45-51.
17 Wirth JP, Rohner F, Woodruff BA, et al.: Anemia, Micronutrient Deficiencies, and Malaria in Children and Women in Sierra Leone Prior to the Ebola Outbreak - Findings of a Cross-Sectional Study. PLoS One 2016; 11: e0155031.
18 Franchini M, Mannucci PM: Impact on human health of climate changes. Eur J Intern Med 2015; 26: 1-5.
19 Cox FE: History of human parasitology. Clin Microbiol Rev 2002; 15: 595-612.
20 Sender R, Fuchs S, Milo R: Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol 2016; 14: e1002533.
21 Cserti-Gazdewich CM, Mayr WR, Dzik WH: Plasmodium falciparum malaria and the immunogenetics of ABO, HLA, and CD36 (platelet glycoprotein IV). Vox Sang 2011; 100: 99-111.
22 Smith JD, Rowe JA, Higgins MK, et al.: Malaria's deadly grip: cytoadhesion of Plasmodium falciparum-infected erythrocytes. Cell Microbiol 2013; 15: 1976-83.
23 Rowe JA, Opi DH, Williams TN: Blood groups and malaria: fresh insights into pathogenesis and identification of targets for intervention. Curr Opin Hematol 2009; 16: 480-7.
24 Cserti-Gazdewich CM, Dhabangi A, Musoke C, et al.: Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection. Br J Haematol 2012; 159: 223-36.
25 Cserti CM, Dzik WH: The ABO blood group system and Plasmodium falciparum malaria. Blood 2007; 110: 2250-8.
26 Miller LH, Ackerman HC, Su XZ, et al.: Malaria biology and disease pathogenesis: insights for new treatments. Nat Med 2013; 19: 156-67.
27 White NJ, Pukrittayakamee S, Hien TT, et al.: Malaria. Lancet 2014; 383: 723-35.
28 Maier AG, Cooke BM, Cowman AF, et al.: Malaria parasite proteins that remodel the host erythrocyte. Nat Rev Microbiol 2009; 7: 341-54.
29 WHO: Severe Malaria. Tropical Medicine and International Health 2014; 19 Supplement: 7-131.
30 Mpimbaza A, Ndeezi G, Katahoire A, et al.: Demographic, Socioeconomic, and Geographic Factors Leading to Severe Malaria and Delayed Care Seeking in Ugandan Children: A Case-Control Study. Am J Trop Med Hyg 2017; 97: 1513-23.
31 Cserti-Gazdewich CM, Dhabangi A, Musoke C, et al.: Inter-relationships of cardinal features and outcomes of symptomatic pediatric Plasmodium falciparum MALARIA in 1,933 children in Kampala, Uganda. Am J Trop Med Hyg 2013; 88: 747-56.
32 Cunnington AJ, Walther M, Riley EM: Piecing together the puzzle of severe malaria. Sci Transl Med 2013; 5: 211ps18.
33 Reyburn H, Mbatia R, Drakeley C, et al.: Association of Transmission Intensity and Age With Clinical Manifestations and Case Fatality of Severe Plasmodium falciparum Malaria. JAMA 2005; 293: 1461-70.
34 Buffet PA, Safeukui I, Deplaine G, et al.: The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology. Blood 2011; 117: 381-92.
35 Taylor SM, Parobek CM, Fairhurst RM: Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12: 457-68.
36 Neafsey DE, Juraska M, Bedford T, et al.: Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine. N Engl J Med 2015; 373: 2025-37.
37 Perkins DJ, Were T, Davenport GC, et al.: Severe malarial anemia: innate immunity and pathogenesis. Int J Biol Sci 2011; 7: 1427-42.
38 Lamikanra AA, Brown D, Potocnik A, et al.: Malarial anemia: of mice and men. Blood 2007; 110: 18-28.
39 Roberts DJ: Hematologic Changes Associated with Specific Infections in the Tropics. Hematol Oncol Clin North Am 2016; 30: 395-415.
40 Jakeman GN, Saul A, Hogarth WL, et al.: Anaemia of acute malaria infections in non-immune patients primarily results from destruction of uninfected erythrocytes. Parasitology 1999; 119 ( Pt 2): 127-33.
41 Burte F, Brown BJ, Orimadegun AE, et al.: Severe childhood malaria syndromes defined by plasma proteome profiles. PLoS One 2012; 7: e49778.
42 Phiri KS, Calis JC, Faragher B, et al.: Long term outcome of severe anaemia in Malawian children. PLoS One 2008; 3: e2903.
43 Hosseini SM, Feng JJ: How malaria parasites reduce the deformability of infected red blood cells. Biophys J 2012; 103: 1-10.
44 Bates I, Bedu-Addo G, Bevan DH, et al.: Use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper-reactive malarial splenomegaly. Lancet 1991; 337: 505-7.
45 Qadri SM, Bissinger R, Solh Z, et al.: Eryptosis in health and disease: A paradigm shift towards understanding the (patho)physiological implications of programmed cell death of erythrocytes. Blood Rev 2017; 31: 349-61.
46 Delves M, Plouffe D, Scheurer C, et al.: The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites. PLoS Med 2012; 9: e1001169.
47 Sowunmi A, Fatunmbi B, Akano K, et al.: Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials. BMC Infect Dis 2017; 17: 781.
48 Biryukov S, Stoute JA: Complement activation in malaria: friend or foe? Trends Mol Med 2014; 20: 293-301.
49 Kai OK, Roberts DJ: The pathophysiology of malarial anaemia: where have all the red cells gone? BMC Med 2008; 6: 24.
50 Chan JA, Howell KB, Reiling L, et al.: Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity. J Clin Invest 2012; 122: 3227-38.
51 Layez C, Nogueira P, Combes V, et al.: Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage. Blood 2005; 106: 3632-8.
52 Chalandon Y, Kocher A: Images in clinical medicine. Severe malaria. N Engl J Med 2000; 342: 1715.
53 McClure NS, Day T: A theoretical examination of the relative importance of evolution management and drug development for managing resistance. Proc Biol Sci 2014; 281.
54 Ashley EA, Dhorda M, Fairhurst RM, et al.: Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2014; 371: 411-23.
55 Karunamoorthi K: The counterfeit anti-malarial is a crime against humanity: a systematic review of the scientific evidence. Malar J 2014; 13: 209.
56 Zhang M, Wang C, Otto TD, et al.: Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science 2018; 360.
57 Demaret P, Tucci M, Ducruet T, et al.: Red blood cell transfusion in critically ill children (CME). Transfusion 2014; 54: 365-75; quiz 4.
58 Shander A, Javidroozi M, Naqvi S, et al.: An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME). Transfusion 2014; 54: 2688-95; quiz 7.
59 English M, Ahmed M, Ngando C, et al.: Blood transfusion for severe anaemia in children in a Kenyan hospital. Lancet 2002; 359: 494-5.
60 van Bommel J, Trouwborst A, Schwarte L, et al.: Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model. Anesthesiology 2002; 97: 660-70.
61 Carson JL, Noveck H, Berlin JA, et al.: Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion. Transfusion 2002; 42: 812-8.
62 Aramburo A, Todd J, George EC, et al.: Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa. BMC Med 2018; 16: 37.
63 Carson JL, Duff A, Poses RM, et al.: Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet 1996; 348: 1055-60.
64 Wolff CB: Normal cardiac output, oxygen delivery and oxygen extraction. Adv Exp Med Biol 2007; 599: 169-82.
65 Bangirana P, Opoka RO, Boivin MJ, et al.: Severe malarial anemia is associated with long-term neurocognitive impairment. Clin Infect Dis 2014; 59: 336-44.
66 Kiguli S, Maitland K, George EC, et al.: Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness. BMC Med 2015; 13: 21.
67 Tobian AA, Ness PM, Noveck H, et al.: Time course and etiology of death in patients with severe anemia. Transfusion 2009; 49: 1395-9.
68 Gbotosho GO, Sowunmi A, Okuboyejo TM, et al.: Therapeutic efficacy and effects of artemether-lumefantrine and artesunate-amodiaquine coformulated or copackaged on malaria-associated anemia in children with uncomplicated Plasmodium falciparum malaria in Southwest Nigeria. Am J Trop Med Hyg 2011; 84: 813-9.
69 Organization. WH: Global status report on blood safety and availability Geneva, World Health Organization, 2016.
70 Lund TC, Hume H, Allain JP, et al.: The blood supply in Sub-Saharan Africa: needs, challenges, and solutions. Transfus Apher Sci 2013; 49: 416-21.
71 Apata IW, Drammeh B, De AK, et al.: Diagnoses and ordering practices driving blood demand for treatment of anemia in Tanzania. Transfusion 2018; 58: 379-89.
72 Tobian AAR, Hume HA: Quest for the holy grail: pathogen reduction in low-income countries. Transfusion 2018; 58: 836-9.
73 Obonyo CO, Steyerberg EW, Oloo AJ, et al.: Blood transfusions for severe malaria-related anemia in Africa: a decision analysis. Am J Trop Med Hyg 1998; 59: 808-12.
74 Allain JP, Assennato SM, Osei EN, et al.: Characterization of posttransfusion Plasmodium falciparum infection in semi-immune nonparasitemic patients. Transfusion 2016; 56: 2374-83.
75 Butler EK, McCullough J: Pathogen reduction combined with rapid diagnostic tests to reduce the risk of transfusion-transmitted infections in Uganda. Transfusion 2018; 58: 854-61.
76 Cserti-Gazdewich C, Dhabangi A, Musoke C, et al.: Transfusion care in the treatment of severe malaria in Uganda: triggers and impact. Transfusion Medicine 2009; 19: 278-9.
77 Dhabangi A, Ainomugisha B, Cserti-Gazdewich C, et al.: Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia: The TOTAL Randomized Clinical Trial. JAMA 2015; 314: 2514-23.
78 Tan KR, Wiegand RE, Arguin PM: Exchange transfusion for severe malaria: evidence base and literature review. Clin Infect Dis 2013; 57: 923-8.
79 Olupot-Olupot P, Engoru C, Thompson J, et al.: Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia. BMC Med 2014; 12: 67.
80 Maitland K, Kiguli S, Opoka RO, et al.: Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364: 2483-95.
81 Zhang DL, Wu J, Shah BN, et al.: Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science 2018; 359: 1520-3.
82 Bates I, Hassall O, Mapako T: Transfusion research priorities for blood services in sub-Saharan Africa. Br J Haematol 2017; 177: 855-63.
83 Custer B, Zou S, Glynn SA, et al.: Addressing gaps in international blood availability and transfusion safety in low- and middle-income countries: a NHLBI workshop. Transfusion 2018; 58: 1307-17.
84 Ala F, Allain JP, Bates I, et al.: External financial aid to blood transfusion services in sub-Saharan Africa: a need for reflection. PLoS Med 2012; 9: e1001309.
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