title: Transfusion-transmitted severe Plasmodium knowlesi malaria in a splenectomized patient with beta-thalassaemia major in Sabah, Malaysia: a case report.
abstract: BACKGROUND
  Transfusion-transmitted malaria (TTM) is a well-recognized risk of receiving blood transfusions, and has occurred with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. The simian parasite Plasmodium knowlesi is also known to be transmissible through inoculation of infected blood, and this species is now the most common cause of malaria in Malaysia with a high rate of severity and fatal cases reported. No confirmed case of accidental transfusion-transmitted P. knowlesi has yet been reported.
  
  
  METHODS
  A 23-year old splenectomized patient with beta thalassaemia major presented with fever 11 days after receiving a blood transfusion from a pre-symptomatic donor who presented with knowlesi malaria 12 days following blood donation. The infection resulted in severe disease in the recipient, with a parasite count of 84,000/µL and associated metabolic acidosis and multi-organ failure. She was treated with intravenous artesunate and made a good recovery. Sequencing of a highly diverse 649-base pair fragment of the P. knowlesi bifunctional dihydrofolate reductase-thymidylate synthase gene (pkdhfr) revealed that the recipient and donor shared the same haplotype.
  
  
  CONCLUSIONS
  This case demonstrates that acquisition of P. knowlesi from blood transfusion can occur, and that clinical consequences can be severe. Furthermore, this case raises the possibility that thalassaemic patients, particularly those who are splenectomized, may represent a high-risk group for TTM and severe malaria. With rising P. knowlesi incidence, further studies in Sabah are required to determine the risk of TTM in order to guide screening strategies for blood transfusion services.
authors.affiliation: Infectious Diseases Society Sabah Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, 88586, Sabah, Malaysia.
authors.forename: Elspeth M
authors.initials: EM
authors.lastname: Bird
authors.affiliation: Infectious Diseases Society Sabah Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, 88586, Sabah, Malaysia.
authors.forename: Uma
authors.initials: U
authors.lastname: Parameswaran
authors.affiliation: Infectious Diseases Society Sabah Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, 88586, Sabah, Malaysia.|Queen Elizabeth Hospital Clinical Research Centre, Kota Kinabalu, 88586, Malaysia.|Jesselton Medical Centre, Kota Kinabalu, 88300, Sabah, Malaysia.
authors.forename: Timothy
authors.initials: T
authors.lastname: William
authors.affiliation: Intensive Care Unit, Queen Elizabeth Hospital, Kota Kinabalu, 88586, Sabah, Malaysia.
authors.forename: Tien Meng
authors.initials: TM
authors.lastname: Khoo
authors.affiliation: Infectious Diseases Society Sabah Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, 88586, Sabah, Malaysia.|Menzies School of Health Research and Charles Darwin University, PO Box 41096, Casuarina, 0810, NT, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Grigg
authors.affiliation: Menzies School of Health Research and Charles Darwin University, PO Box 41096, Casuarina, 0810, NT, Australia.
authors.forename: Ammar
authors.initials: A
authors.lastname: Aziz
authors.affiliation: Menzies School of Health Research and Charles Darwin University, PO Box 41096, Casuarina, 0810, NT, Australia.
authors.forename: Jutta
authors.initials: J
authors.lastname: Marfurt
authors.affiliation: Infectious Diseases Society Sabah Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, 88586, Sabah, Malaysia.|Menzies School of Health Research and Charles Darwin University, PO Box 41096, Casuarina, 0810, NT, Australia.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 639798, Singapore.
authors.forename: Tsin W
authors.initials: TW
authors.lastname: Yeo
authors.affiliation: Menzies School of Health Research and Charles Darwin University, PO Box 41096, Casuarina, 0810, NT, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Auburn
authors.affiliation: Infectious Diseases Society Sabah Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, 88586, Sabah, Malaysia.|Menzies School of Health Research and Charles Darwin University, PO Box 41096, Casuarina, 0810, NT, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.affiliation: Infectious Diseases Society Sabah Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, 88586, Sabah, Malaysia. bridget.barber@menzies.edu.au.|Menzies School of Health Research and Charles Darwin University, PO Box 41096, Casuarina, 0810, NT, Australia. bridget.barber@menzies.edu.au.
authors.forename: Bridget E
authors.identifier: http://orcid.org/0000-0003-1066-7960
authors.initials: BE
authors.lastname: Barber
mesh_terms: D061605:Administration, Intravenous; D037621:Artemisinins / Q000008:administration & dosage; D000077332:Artesunate; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000635:transmission*; D008296:Malaysia; D016790:Plasmodium knowlesi / Q000145:classification / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification*; D013156:Splenectomy; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D065227:Transfusion Reaction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D037621:Artemisinins; D000077332:Artesunate; D013762:Tetrahydrofolate Dehydrogenase
keywords: Beta thalassemia; Borneo; Malaria transmission; PCR; Plasmodium knowlesi; Sabah; Severe malaria; Splenectomy; Transfusion-transmitted malaria