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Blackwater fever like in murine malaria

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Abstract

Blackwater fever (BWF) is the term used to designate the occurrence of hemoglobin pigments in the urine of patients infected with malaria parasites. BWF is more often associated with Plasmodium falciparum infection in man. The pathogenesis of BWF has not been explained satisfactorily. In the present study, the clinical and pathological observations made upon CD1 mice infected with Plasmodium yoelii yoelii lethal strain with clinical signs of hemoglobinuria and acute renal failure were evaluated. From the 40 P. yoelii yoelii-infected mice, 14 presented hemoglobinuria. In the observations, it was emphasized that hemoglobinuria occurred in the animals 1–2 days before they die. At 6 days post-infection, infected hemoglobinuric mice (HM) exhibited clinical signs such as dark red urine, apnea, and evident oliguria and hematuria; urine microscopical examination showed very few red blood cells. The entire non hemoglobinuric infected mice had a high parasitemia preceding the time of death, while the HM parasitemia was just detectable. In HM, marked hepatosplenomegaly, anemia, and renal and hepatic dysfunction were observed with the blood chemistry analysis at 6 days post-infection. Severe renal lesions were demonstrated in histopathological and scanning electron microscopy samples. Occlusion and necrosis of convoluted tubules were the main lesions found. The conditions required for the experimental production of hemoglobinuria in CD1 mouse infected by P. yoelii yoelii is still unknown. The clinical picture of a BWF, like in our rodents, was produced exclusively by the interaction between the parasite and its host. Results showed that hemoglobinuria in CD1 mice infected with P. yoelii yoelii and BWF in man infected with P. falciparum are similar in their pathogenesis.

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References

  • Blackie WK (1994) Blackwater fever. Clin Proc 11:272–273

    Google Scholar 

  • Brown WH (1913) Malaria pigment (hematin) as an active factor in the production of the blood picture of malaria. J Exp Med 18(1):96–106

    Article  PubMed  CAS  Google Scholar 

  • Bruce-Chwatt LJ (1987) Quinine and the mystery of blackwater fever. Acta Leidensia 55:181–196

    PubMed  CAS  Google Scholar 

  • Bruce-Chwatt LJ (1980) Essential malariology, 1st edn. Heinemann, London, p 69

    Google Scholar 

  • Bruneel F, Gachot B, Wolff M, Bedos JP, Regnier B, Danis M, Vachon F (2002) Blackwater fever. Presse Med 31(28):1329–1334

    PubMed  CAS  Google Scholar 

  • Bruneel F, Gachot B, Wolff M, Régnier B, Danis M, Vachon F (2001) Resurgence of blackwater fever in long-term European expatriates in Africa: report of 21 cases and review. Clin Infect Dis 32(8):1133–1140

    Article  PubMed  CAS  Google Scholar 

  • Craig GA, Grau EG, Janse C et al (2012) The role of animal models for research on severe malaria. Plos Pathogens 8:1–9

    Article  Google Scholar 

  • Chau TT, Nicholas PJ, Choung DL et al (1996) Blackwater fever in southern Vietnam: a prospective descriptive study of 50 cases. Clin Infect Dis 23(6):1274–1281

    Article  Google Scholar 

  • Das BS (2008) Renal failure in malaria. J Vector Borne Dis 45:83–97

    PubMed  CAS  Google Scholar 

  • Donovan J, Brown P (2006) Euthanasia. Curr Protoc Immunol Jul; chapter 1: unit 1.8, pp 1.8.1.–1.8.4

  • Dukes DC, Sealey BJ, Forbes N (1968) Oliguric renal failure in blackwater fever. Am J Med 45:899–903

    Article  PubMed  CAS  Google Scholar 

  • Elsheikha MH, Sheashaa AH (2007) Epidemiology, pathophysiology, management and outcome of renal dysfunction associated with plasmodia infection. Parasitol Res 101:1183–1190

    Article  PubMed  Google Scholar 

  • Fairley NH, Murgatroyd F (1940) Recurrent blackwater fever induced by quinine. Trans R Soc Trop Med Hyg 34:187–194

    Article  CAS  Google Scholar 

  • Findlay GM (1949) Blackwater fever in West Africa, 1941–1945. II. Blackwater fever in African military personnel. Ann Trop Med Parasitol 43:213–224

    PubMed  CAS  Google Scholar 

  • Findlay G, Markson J (1947) Attempts to induce blackwater fever experimentally. Ann Trop Med ParasitoI 41:22–25

    CAS  Google Scholar 

  • Ganesan S, Tekwani BL, Sahu R, Tripathi LM, Walker LA (2009) Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol 241(1):14–22

    Article  PubMed  CAS  Google Scholar 

  • Gobbi F, Audagnotto L, Nkurunziza I et al (2005) Blackwater fever in children. Burundi Emerg Infec Dis 11(7):1118–1120

    Article  Google Scholar 

  • Graça-Souza AV, Arruda MA, de Freitas MS, Barja-Fidalgo C, Oliveira PL (2002) Neutrophil activation by heme: implications for inflammatory processes. Blood 99(11):4160–4165

    Article  PubMed  Google Scholar 

  • Ghosh K, Ghosh K (2007) Pathogenesis of anemia in malaria: a concise review. Parasitol Res 101:1463–1469

    Article  PubMed  Google Scholar 

  • Hoff J (2000) Methods of blood collection in the mouse. Lab Animal 29(10):1–7

    Google Scholar 

  • James JA, Gross T, Scofield RH, Harley JB (1995) Immunoglobin epitope spreading and autoimmune disease after peptide immunization: Sm BjB′-derived PPPGMRPP and PPPGIRGP induce spliceosome autoimmunity. J of Expl Med 181:453–461

    Article  CAS  Google Scholar 

  • Jiménez BC, Cuadros-Tito P, Ruiz-Giardin JM, Rojo-Marcos G, Cuadros-González J, Canalejo E, Cabello N, San Martín JV, Barrios AM, Hinojosa J, Molina L (2012) Imported malaria in pregnancy in Madrid. Malar J 11:112

    Article  PubMed  Google Scholar 

  • Kakoma I, James MA, Whiteley HE, Montelegre F, Buese M, Fafjar-Whestone CJ, Clabaugh GW, Baek BK (1992) Platelet kinetics and other hematological profiles in experimental Plasmodium falciparum infection: a comparative study between Saimiri and Aotus monkeys. Kisaengchunghak Chapchi Sep 30(3):177–182

    CAS  Google Scholar 

  • Lameire N, Vanholder R (2001) Pathophysiologic features and prevention of human and experimental acute tubular necrosis. J Am Soc Nephrol 12:20–32

    Google Scholar 

  • Manan JA, Ali H, Manohar Lal M (2006) Acute renal failure associated with malaria. J Ayub Med Coll Abbottabad 18:47–52

    PubMed  Google Scholar 

  • Maegraith BG (1948) Pathological processes in malaria blackwater fever. Blackwell, Oxford, p 430

    Google Scholar 

  • Moll K, Ljungström I, Perlmann H, Scherf A, Wahlgren M (2008) Methods in malaria research. 5th edition. http://www.biomalpar.org/updatedMethodsIn_Malaria_Research_5thedition.pdf.. Accessed: 7 Aug 2012

  • Murthy GL, Sahay RK, Sreenivas DV, Sundaram C, Shantaram V (1998) Hepatitis in falciparum malaria. Trop Gastroenterol 19:152–154

    PubMed  CAS  Google Scholar 

  • Nacher M, Treeprasertsuk S, Singhasivanon P, Silachamroon U, Vannaphan S, Gay F, Looareesuwan S et al (2001) Association of hepatomegaly and jaundice with acute renal failure but not with cerebral malaria in severe falciparum malaria in Thailand. AmJTrop Med Hyg 65:828–833

    CAS  Google Scholar 

  • Nguansangiam S, Day NPJ, Hien TT, Mai NTH, Chaisri U, Riganti M (2007) A quantitative ultrastructural study of renal pathology in fatal Plasmodium falciparum malaria. Trop Med Int Heal 12:1037–1050

    Article  Google Scholar 

  • Parakash J, Singh AK, Kumar NS, Saxene RK (2003) Acute renal failure in Plasmodium vivax malaria. J Assoc Physicians India 51:265–267

    Google Scholar 

  • Patel PM, Kute BV, Gumber RM, Gera ND, Shan RP, Patel VH, Trivedi LH, Vanikar VA (2012) An unusual case of Plasmodium vivax malaria monoinfection associated with crescentic glomerulonephritis: a need for vigilance. Parasitol Res. doi:10.1007/s00436-012-3040-5

  • Peterson A, Calamandrei E (eds) (2012) Malaria, etiology, pathogenesis and treatment, 1st edn. Nova Science, New York, p 1

    Google Scholar 

  • Rigdon RH (1948) Haemoglobinuria (blackwater fever) in monkeys a consideration of the disease in man. Am J Pathol 25(2):195–209

    Google Scholar 

  • Stephens J (1937) Blackwater fever: a historical survey and summary of observations made over a century, chapter 8. University Press, Liverpool, England, p 165

    Google Scholar 

  • Thomson JG (1924) Researches on blackwater fever in Southern Rhodesia. Proc R Soc Med 17:47–63

    PubMed  CAS  Google Scholar 

  • Tobón CA, Cortina A, Miranda AF, Trujillo BS (2010) Orina oscura e ictericia como signos de peligro en malaria por Plasmodium falciparum en Colombia. Rev Cubana Med Trop 62(1):28–35

    Google Scholar 

  • Tombe M (2008) Hemoglobinuria with malaria. N Eng J Med 358(17):1837

    Article  CAS  Google Scholar 

  • World Health Organization, Division of Control of Tropical Diseases (1990) Severe and complicated malaria. Trans R Soc Trop Med Hyg 84(Suppl 2):1–65

    Article  Google Scholar 

  • World Health Organization (2000) Severe falciparum malaria. Trans R Soc Trop Med Hyg 94(Suppl1):S1–S74

    Article  Google Scholar 

Download references

Acknowledgments

This research was partially supported by the Department of Microbiology and Parasitology, Faculty of Medicine, UNAM, and by project PAPIIT-DGAPA IN-229611, UNAM. The partial support by the Department of Pathology, FMVZ, UNAM is also gratefully acknowledged. The authors thank Cecilia Martinez Castillo and Francisco Pasos Nájera for their technical assistance. We also appreciate the technical assistance of Enrique Pinzón Estrada. This study complies with the current laws of Mexico.

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Correspondence to Norma Rivera.

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Rivera, N., Romero, S.E., Menchaca, Á. et al. Blackwater fever like in murine malaria. Parasitol Res 112, 1021–1029 (2013). https://doi.org/10.1007/s00436-012-3224-z

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