DISSEMINATED INTRAVASCULAR COAGULATION COMPLICATED BY PERIPHERAL GANGRENE IN A RHESUS MACAQUE (MACACA MULATTA) EXPERIMENTALLY INFECTED WITH PLASMODIUM COATNEYI

ALBERTO MORENO Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia

Search for other papers by ALBERTO MORENO in
Current site
Google Scholar
PubMed
Close
,
ANAPATRICIA GARCÍA Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia

Search for other papers by ANAPATRICIA GARCÍA in
Current site
Google Scholar
PubMed
Close
,
MÓNICA CABRERA-MORA Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia

Search for other papers by MÓNICA CABRERA-MORA in
Current site
Google Scholar
PubMed
Close
,
ELIZABETH STROBERT Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia

Search for other papers by ELIZABETH STROBERT in
Current site
Google Scholar
PubMed
Close
, and
MARY R. GALINSKI Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia

Search for other papers by MARY R. GALINSKI in
Current site
Google Scholar
PubMed
Close
Restricted access

We report the first case of disseminated intravascular coagulation (DIC) complicated by peripheral gangrene induced by Plasmodium coatneyi in rhesus monkeys. Ten days after experimental challenge, numerous petechiae were noted over the trunk and extremities, with polychromasia, severe anemia, thrombocytopenia, and moderate parasitemia. These changes were accompanied by elevated serum activity of blood urea nitrogen, creatinine, transaminases, and creatinine phosphokinase. The animal received intravenous fluid support, artemether, and blood transfusion. Three days after treatment, the platelet counts returned to normal, and parasitemia was abated. However, several areas of skin discoloration with gangrenous tissue in the hands and the tail were observed. Coagulation profile showed elevated D-dimers and elevated levels of fibrinogen/fibrin degradation products with low levels of protein S functional activity. DIC with peripheral gangrene is very rare in Plasmodium-infected individuals. Our results indicate that the experimental model of P. coatneyi infection of rhesus monkeys is important for studies of malarial anemia and coagulopathy.

Author Notes

Reprint requests: Alberto Moreno, Emory Vaccine Center, Yerkes National Primate Research Center and Division of Infectious Diseases, Department of Medicine, Emory University, 954 Gatewood Rd., Atlanta, GA 30329. E-mail: amoreno@rmy.emory.edu.
  • 1

    Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI, 2005. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434 :214–217.

  • 2

    Vythilingam I, Tan CH, Asmad M, Chan ST, Lee KS, Singh B, 2006. Natural transmission of Plasmodium knowlesi to humans by Anopheles latens in Sarawak, Malaysia. Trans R Soc Trop Med Hyg 100 :1087–1088.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Jongwutiwes S, Putaporntip C, Iwasaki T, Sata T, Kanbara H, 2004. Naturally acquired Plasmodium knowlesi malaria in human, Thailand. Emerg Infect Dis 10 :2211–2213.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, Thomas A, Conway DJ, 2004. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 363 :1017–1024.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, Newton C, Winstanley P, Warn P, Peshu N, 1995. Indicators of life-threatening malaria in African children. N Engl J Med 332 :1399–1404.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Brabin BJ, Premji Z, Verhoeff F, 2001. An analysis of anemia and child mortality. J Nutr 131 :636S–645S.

  • 7

    Snow RW, Omumbo JA, Lowe B, Molyneux CS, Obiero JO, Palmer A, Weber MW, Pinder M, Nahlen B, Obonyo C, New-bold C, Gupta S, Marsh K, 1997. Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa. Lancet 349 :1650–1654.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    WHO, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 :S1–90.

  • 9

    Greenwood BM, Bradley AK, Greenwood AM, Byass P, Jammeh K, Marsh K, Tulloch S, Oldfield FS, Hayes R, 1987. Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa. Trans R Soc Trop Med Hyg 81 :478–486.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Fleming AF, 1989. Tropical obstetrics and gynaecology. 1. Anaemia in pregnancy in tropical Africa. Trans R Soc Trop Med Hyg 83 :441–448.

  • 11

    Trang TT, Phu NH, Vinh H, Hien TT, Cuong BM, Chau TT, Mai NT, Waller DJ, White NJ, 1992. Acute renal failure in patients with severe falciparum malaria. Clin Infect Dis 15 :874–880.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Berendt AR, Ferguson DJ, Gardner J, Turner G, Rowe A, McCormick C, Roberts D, Craig A, Pinches R, Elford BC, et al., 1994. Molecular mechanisms of sequestration in malaria. Parasitology 108 (Suppl):S19–S28.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Gysin J, 1991. Relevance of the squirrel monkey as a model for experimental human malaria. Res Immunol 142 :649–654.

  • 14

    Schmidt LH, 1973. Infections with Plasmodium falciparum and Plasmodium vivax in the owl monkey–model systems for basic biological and chemotherapeutic studies. Trans R Soc Trop Med Hyg 67 :446–474.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Young MD, Baerg DC, Rossan RN, 1976. Studies with induced malarias in Aotus monkeys. Lab Anim Sci 26 :1131–1137.

  • 16

    Collins WE, 1992. South American monkeys in the development and testing of malarial vaccines—a review. Mem Inst Oswaldo Cruz 87 (Suppl 3):401–406.

  • 17

    Kawai S, Aikawa M, Kano S, Suzuki M, 1993. A primate model for severe human malaria with cerebral involvement: Plasmodium coatneyi-infected Macaca fuscata. Am J Trop Med Hyg 48 :630–636.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Davison BB, Cogswell FB, Baskin GB, Falkenstein KP, Henson EW, Tarantal AF, Krogstad DJ, 1998. Plasmodium coatneyi in the rhesus monkey (Macaca mulatta) as a model of malaria in pregnancy. Am J Trop Med Hyg 59 :189–201.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Egan AF, Fabucci ME, Saul A, Kaslow DC, Miller LH, 2002. Aotus New World monkeys: model for studying malaria-induced anemia. Blood 99 :3863–3866.

  • 20

    Makobongo MO, Keegan B, Long CA, Miller LH, 2006. Immunization of Aotus monkeys with recombinant cysteine-rich interdomain region 1 alpha protects against severe disease during Plasmodium falciparum reinfection. J Infect Dis 193 :731–740.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Eyles DE, Fong YL, Warren M, Guinn E, Sandosham AA, Wharton RH, 1962. Plasmodium coatneyi, a new species of primate malaria from Malaya. Am J Trop Med Hyg 11 :597–604.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Vargas-Serrato E, Corredor V, Galinski MR, 2003. Phylogenetic analysis of CSP and MSP-9 gene sequences demonstrates the close relationship of Plasmodium coatneyi to Plasmodium knowlesi. Infect Genet Evol 3 :67–73.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Desowitz RS, Miller LH, Buchanan RD, Permpanich B, 1969. The sites of deep vascular schizogony in Plasmodium coatneyi malaria. Trans R Soc Trop Med Hyg 63 :198–202.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Smith CD, Brown AE, Nakazawa S, Fujioka H, Aikawa M, 1996. Multi-organ erythrocyte sequestration and ligand expression in rhesus monkeys infected with Plasmodium coatneyi malaria. Am J Trop Med Hyg 55 :379–383.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Aikawa M, Brown AE, Smith CD, Tegoshi T, Howard RJ, Hasler TH, Ito Y, Collins WE, Webster HK, 1992. Plasmodium coatneyi-infected rhesus monkeys: a primate model for human cerebral malaria. Mem Inst Oswaldo Cruz 87 (Suppl 3):443–447.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Liechti ME, Zumsteg V, Hatz CF, Herren T, 2003. Plasmodium falciparum cerebral malaria complicated by disseminated intravascular coagulation and symmetrical peripheral gangrene: case report and review. Eur J Clin Microbiol Infect Dis 22 :551–554.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Riley RS, Ben-Ezra JM, Tidwell A, Romagnoli G, 2002. Reticulocyte analysis by flow cytometry and other techniques. Hematol Oncol Clin North Am 16 :373–420.

  • 28

    Momotani E, Yabuki Y, Miho H, Ishikawa Y, Yoshino T, 1985. Histopathological evaluation of disseminated intravascular coagulation in Haemophilus somnus infection in cattle. J Comp Pathol 95 :15.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Collins WE, Warren M, Sullivan JS, Galland GG, 2001. Plasmodium coatneyi: observations on periodicity, mosquito infection, and transmission to Macaca mulatta monkeys. Am J Trop Med Hyg 64 :101–110.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Salord F, Allaouchiche B, Gaussorgues P, Boibieux A, Sirodot M, Gerard-Boncompain M, Biron F, Peyramond D, Robert D, 1991. Severe falciparum malaria (21 cases). Intensive Care Med 17 :449–454.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Bruneel F, Hocqueloux L, Alberti C, Wolff M, Chevret S, Bedos JP, Durand R, Le Bras J, Regnier B, Vachon F, 2003. The clinical spectrum of severe imported falciparum malaria in the intensive care unit: report of 188 cases in adults. Am J Respir Crit Care Med 167 :684–689.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Losert H, Schmid K, Wilfing A, Winkler S, Staudinger T, Kletzmayr J, Burgmann H, 2000. Experiences with severe P. falciparum malaria in the intensive care unit. Intensive Care Med 26 :195–201.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Schofield L, Grau GE, 2005. Immunological processes in malaria pathogenesis. Nat Rev Immunol 5 :722–735.

  • 34

    Coatney GR, 1968. Simian malarias in man: facts, implications, and predictions. Am J Trop Med Hyg 17 :147–155.

  • 35

    Udomsangpetch R, Brown AE, Smith CD, Webster HK, 1991. Rosette formation by Plasmodium coatneyi-infected red blood cells. Am J Trop Med Hyg 44 :399–401.

  • 36

    Aikawa M, Brown A, Smith CD, Tegoshi T, Howard RJ, Hasler TH, Ito Y, Perry G, Collins WE, Webster K, 1992. A primate model for human cerebral malaria: Plasmodium coatneyi-infected rhesus monkeys. Am J Trop Med Hyg 46 :391–397.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Sein KK, Brown AE, Maeno Y, Smith CD, Corcoran KD, Hansukjariya P, Webster HK, Aikawa M, 1993. Sequestration pattern of parasitized erythrocytes in cerebrum, mid-brain, and cerebellum of Plasmodium coatneyi-infected rhesus monkeys (Macaca mulatta). Am J Trop Med Hyg 49 :513–519.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Nakano Y, Fujioka H, Luc KD, Rabbege JR, Todd GD, Collins WE, Aikawa M, 1996. A correlation of the sequestration rate of Plasmodium coatneyi-infected erythrocytes in cerebral and subcutaneous tissues of a rhesus monkey. Am J Trop Med Hyg 55 :311–314.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Yu M, Nardella A, Pechet L, 2000. Screening tests of disseminated intravascular coagulation: guidelines for rapid and specific laboratory diagnosis. Crit Care Med 28 :1777–1780.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Vogetseder A, Ospelt C, Reindl M, Schober M, Schmutzhard E, 2004. Time course of coagulation parameters, cytokines and adhesion molecules in Plasmodium falciparum malaria. Trop Med Int Health 9 :767–773.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Mohanty D, Ghosh K, Nandwani SK, Shetty S, Phillips C, Rizvi S, Parmar BD, 1997. Fibrinolysis, inhibitors of blood coagulation, and monocyte derived coagulant activity in acute malaria. Am J Hematol 54 :23–29.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Hemmer CJ, Kern P, Holst FG, Radtke KP, Egbring R, Bierhaus A, Nawroth PP, Dietrich M, 1991. Activation of the host response in human Plasmodium falciparum malaria: relation of parasitemia to tumor necrosis factor/cachectin, thrombin-antithrombin III, and protein C levels. Am J Med 91 :37–44.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Mohanty D, Marwaha N, Ghosh K, Sharma S, Garewal G, Shah S, Devi S, Das KC, 1988. Functional and ultrastructural changes of platelets in malarial infection. Trans R Soc Trop Med Hyg 82 :369–375.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Grau GE, Piguet PF, Gretener D, Vesin C, Lambert PH, 1988. Immunopathology of thrombocytopenia in experimental malaria. Immunology 65 :501–506.

  • 45

    Yamaguchi S, Kubota T, Yamagishi T, Okamoto K, Izumi T, Takada M, Kanou S, Suzuki M, Tsuchiya J, Naruse T, 1997. Severe thrombocytopenia suggesting immunological mechanisms in two cases of vivax malaria. Am J Hematol 56 :183–186.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46

    Lee SH, Looareesuwan S, Chan J, Wilairatana P, Vanijanonta S, Chong SM, Chong BH, 1997. Plasma macrophage colony-stimulating factor and P-selectin levels in malaria-associated thrombocytopenia. Thromb Haemost 77 :289–293.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Jaff MS, McKenna D, McCann SR, 1985. Platelet phagocytosis: a probable mechanism of thrombocytopenia in Plasmodium falciparum infection. J Clin Pathol 38 :1318–1319.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48

    Skudowitz RB, Katz J, Lurie A, Levin J, Metz J, 1973. Mechanisms of thrombocytopenia in malignant tertian malaria. BMJ 2 :515–518.

  • 49

    Erel O, Vural H, Aksoy N, Aslan G, Ulukanligil M, 2001. Oxidative stress of platelets and thrombocytopenia in patients with vivax malaria. Clin Biochem 34 :341.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50

    Winograd E, Prudhomme JG, Sherman IW, 2005. Band 3 clustering promotes the exposure of neoantigens in Plasmodium falciparum-infected erythrocytes. Mol Biochem Parasitol 142 :98.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51

    Moll GN, Vial HJ, Bevers EM, Ancelin ML, Roelofsen B, Comfurius P, Slotboom AJ, Zwaal RF, Op den Kamp JA, van Deenen LL, 1990. Phospholipid asymmetry in the plasma membrane of malaria infected erythrocytes. Biochem Cell Biol 68 :579–585.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52

    Simoes AP, Moll GN, Beaumelle B, Vial HJ, Roelofsen B, Op den Kamp JA, 1990. Plasmodium knowlesi induces alterations in phosphatidylcholine and phosphatidylethanolamine molecular species composition of parasitized monkey erythrocytes. Biochim Biophys Acta 1022 :135–145.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53

    Sherman IW, Eda S, Winograd E, 2003. Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. Microbes Infect 5 :897–909.

  • 54

    Manodori AB, Barabino GA, Lubin BH, Kuypers FA, 2000. Adherence of phosphatidylserine-exposing erythrocytes to endothelial matrix thrombospondin. Blood 95 :1293–1300.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55

    Conway EM, Bach R, Rosenberg RD, Konigsberg WH, 1989. Tumor necrosis factor enhances expression of tissue factor mRNA in endothelial cells. Thromb Res 53 :231–241.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56

    Imamura T, Sugiyama T, Cuevas LE, Makunde R, Nakamura S, 2002. Expression of tissue factor, the clotting initiator, on macrophages in Plasmodium falciparum-infected placentas. J Infect Dis 186 :436–440.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57

    Turner GD, Ly VC, Nguyen TH, Tran TH, Nguyen HP, Bethell D, Wyllie S, Louwrier K, Fox SB, Gatter KC, Day NP, Tran TH, White NJ, Berendt AR, 1998. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol 152 :1477–1487.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58

    Hollestelle MJ, Donkor C, Mantey EA, Chakravorty SJ, Craig A, Akoto AO, O’Donnell J, van Mourik JA, Bunn J, 2006. von Willebrand factor propeptide in malaria: evidence of acute endothelial cell activation. Br J Haematol 133 :562–569.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59

    Weiss SJ, 1989. Tissue destruction by neutrophils. N Engl J Med 320 :365–376.

  • 60

    Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM, 1998. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91 :3527–3561.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61

    Warren JD, Blumbergs PC, Thompson PD, 2002. Rhabdomyolysis: a review. Muscle Nerve 25 :332–347.

  • 62

    Davis TM, Pongponratan E, Supanaranond W, Pukrittayakamee S, Helliwell T, Holloway P, White NJ, 1999. Skeletal muscle involvement in falciparum malaria: biochemical and ultrastructural study. Clin Infect Dis 29 :831–835.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63

    St. John A, Davis TM, Binh TQ, Thu LT, Dyer JR, Anh TK, 1995. Mineral homoeostasis in acute renal failure complicating severe falciparum malaria. J Clin Endocrinol Metab 80 :2761–2767.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64

    Allo JC, Vincent F, Barboteu M, Schlemmer B, 1997. Falciparum malaria: an infectious cause of rhabdomyolysis and acute renal failure. Nephrol Dial Transplant 12 :2033–2034.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 65

    Knochel JP, Moore GE, 1993. Rhabdomyolysis in malaria. N Engl J Med 329 :1206–1207.

  • 66

    Reynaud F, Mallet L, Lyon A, Rodolfo JM, 2005. Rhabdomyolysis and acute renal failure in Plasmodium falciparum malaria. Nephrol Dial Transplant 20 :847.

  • 67

    Sinniah R, Lye W, 2000. Acute renal failure from myoglobinuria secondary to myositis from severe falciparum malaria. Am J Nephrol 20 :339–343.

  • 68

    Taylor WR, Prosser DI, 1992. Acute renal failure, acute rhabdomyolysis and falciparum malaria. Trans R Soc Trop Med Hyg 86 :361.

  • 69

    Rosen S, Hano JE, Inman MM, Gilliland PF, Barry KG, 1968. The kidney in blackwater fever: light and electron microscopic observations. Am J Clin Pathol 49 :358–370.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 70

    Singh U, Scheld WM, 1996. Infectious etiologies of rhabdomyolysis: three case reports and review. Clin Infect Dis 22 :642–649.

  • 71

    Earle WC, Perez M, 1932. Enumeration of parasites in the blood of malarial patients. J Lab Clin Med 17 :1124–1130.

Past two years Past Year Past 30 Days
Abstract Views 42 42 5
Full Text Views 317 4 2
PDF Downloads 77 2 2
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save