Volume 95, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century. Compliance was difficult to enforce even in organized groups such as the military, and its prophylaxis potential was often questioned. Severe adverse events such as blackwater fever occurred rarely, but its relationship to quinine remains uncertain. Quinine prophylaxis was often counterproductive from a public health viewpoint as it left large numbers of persons with suppressed infections producing gametocytes infective for mosquitoes. Quinine was supplied by the first global pharmaceutical cartel which discouraged competition resulting in a near monopoly of cinchona plantations on the island of Java which were closed to Allied use when the Japanese Imperial Army captured Indonesia in 1942. The problems with quinine as a chemoprophylactic drug illustrate the difficulties with medications used for prevention and the acute need for improved compounds.


Article metrics loading...

Loading full text...

Full text loading...



  1. Ross R, , 1918. An interim report on the treatment of malaria: abstract of 2,460 cases. War Office Investigations. Trans R Soc Trop Med Hyg 11: 179204.[Crossref]
  2. Ross R, , 1910. The Prevention of Malaria. London, United Kingdom: Dutton.
  3. Findlay G, Stevenson A, , 1944. Investigations in the chemotherapy of malaria in west Africa. II. Malaria suppression: quinine and mepacrine. Ann Trop Med Parasitol 38: 168187.[Crossref]
  4. Sappington J, , 1844. The Theory and Treatment of Fevers. St Louis, MO: J. Sappington.
  5. Brown WC, , 1911. The present position of the quinine prophylaxis of malaria. Trans R Soc Trop Med Hyg 4: 193209.[Crossref]
  6. Thomson J, , 1917. Quinine in malaria: its limitations and possibilities. Trans R Soc Trop Med Hyg 11: 226231.[Crossref]
  7. James SP, , 1920. Malaria at Home and Abroad. London, United Kingdom: John Bale Sons and Danielsson.
  8. Christophers S, Shortt H, , 1921. Incidence of malaria among troops in Mesopotamia, 1916–1919. Indian J Med Res 8: 553570.
  9. Wenyon CM, Anderson A, McLay K, Hele T, Waterston J, , 1921. Malaria in Macedonia, 1915–1919. J R Army Med Corps 37: 8182.
  10. Macpherson WG, Herringham W, Elliott T, Balfour A, , 1922. History of the Great War Based on Official Documents. Medical Services. Diseases of the War, Vol. 1. London, United Kingdom: His Majesty's Stationery Office.
  11. Christophers SR, , 1939. Malaria in war. Trans R Soc Trop Med Hyg 33: 277292.[Crossref]
  12. Sinton JA, , 1946. Malaria in war. Ulster Med J 15: 328.
  13. Bruce-Chwatt LJ, , 1985. John Hull Grundy lecture. Mosquitoes, malaria and war; then and now. J R Army Med Corps 131: 8599.[Crossref]
  14. Christophers SR, Bentley CA, , 1908. Black-Water Fever. Calcutta, India: Office of the Superintendent of Government Printing.
  15. Deeks WE, James WM, , 1911. A Report on Hemoglobinuric Fever in the Canal Zone: A Study of Its Etiology and Treatment. Mount Hope, Canal Zone: I.C.C. Press.
  16. Phear A, , 1920. Notes on blackwater fever in Macedonia. J R Army Med Corps 34: 114.
  17. Stephens JWW, , 1937. Blackwater Fever. London, United Kingdom: Hodder and Stoughton.
  18. Chau TTH, Day NP, Van Chuong L, Mai NTH, Loc PP, Phu NH, Bethell DB, Sinh DX, Hien TT, White NJ, , 1996. Blackwater fever in southern Vietnam: a prospective descriptive study of 50 cases. Clin Infect Dis 23: 12741281.[Crossref]
  19. Wells TN, van Huijsduijnen RH, Van Voorhis WC, , 2015. Malaria medicines: a glass half full? Nat Rev Drug Discov 14: 424442.[Crossref]
  20. Duran-Reynals ML, , 1947. The Fever Bark Tree. New York, NY: Doubleday.
  21. Honigsbaum M, , 2003. The Fever Trail: In Search of the Cure for Malaria. New York, NY: Picador.
  22. Kligler IJ, , 1923. Quinine prophylaxis and latent malaria infection. Trans R Soc Trop Med Hyg 17: 259262.[Crossref]
  23. Gorgas WC, , 1915. Sanitation in Panama. New York, NY: Appleton.
  24. Duncan A, , 1888. The Prevention of Disease in Tropical and Subtropical Campaigns. London, United Kingdom: J. A. Churchill.
  25. Balfour A, , 1919. Memoranda on Medical Diseases in the Tropical and Sub-tropical War Areas. London, United Kingdom: His Majesty's Stationery Office.
  26. Hehir P, , 1927. Malaria in India. London, United Kingdom: Oxford University Press.
  27. Ross R, , 1897. On some peculiar pigmented cells found in two mosquitos fed on malarial blood. BMJ 2: 1786.[Crossref]
  28. Laveran A, , 1907. Traite du Paludisme. Paris, France: Masson.
  29. Sternberg GM, , 1884. Malaria and Malarial Diseases. New York, NY: Wood Library of Standard Medical Authors.
  30. James SP, , 1903. Report of the Anti-Malarial Operations at Mian Mir, 1901–1903. Calcutta, India: Office of the Superintendent of Government Printing.
  31. Christophers SR, , 1904. Second Report of the Anti-Malarial Operations at Mian Mir, 1901–1903. Calcutta, India: Office of the Superintendent of Government Printing, India.
  32. Snowden F, , 2008. The Conquest of Malaria: Italy, 1900–1962. New Haven, CT: Yale University Press.
  33. Christophers SR, , 1942. The treatment of malaria and some points about the drugs in use against this disease. Trans R Soc Trop Med Hyg 36: 4959.[Crossref]
  34. Findlay G, , 1949. Blackwater fever in west Africa, 1941–45; blackwater fever in European military personnel. Ann Trop Med Parasitol 43: 140154.[Crossref]
  35. Findlay G, , 1949. Blackwater fever in west Africa; 1941–45; blackwater fever in African military personnel. Ann Trop Med Parasitol 43: 213224.[Crossref]
  36. Covell G, , 1943. The prophylaxis and treatment of malaria in war. J Malar Inst India 5: 129157.
  37. Peatey CL, Skinner-Adams TS, Dixon MWA, McCarthy JS, Gardiner DL, Trenholme KR, , 2009. Effect of antimalarial drugs on Plasmodium falciparum gametocytes. J Infect Dis 200: 15181521.[Crossref]
  38. Watson M, , 1924. Observations on malaria control, with special reference to the Assam Tea Gardens, and some remarks on Mian Mir, Lahore Cantonment. Trans R Soc Trop Med Hyg 18: 147161.[Crossref]
  39. Taylor N, , 1945. Cinchona in Java. New York, NY: Greenberg.
  40. Goss A, , 2014. Building the world's supply of quinine: Dutch colonialism and the origins of a global pharmaceutical industry. Endeavour 38: 818.[Crossref]
  41. Sweeney T, , 2003. Malaria Frontline: Australian Army Research during World War II. Melbourne, Australia: Melbourne University Press.
  42. Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, Krudsood S, Gupta SK, Kochar SK, Arthur P, Chuenchom N, Möhrle JJ, Duparc S, , 2014. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet 383: 10491058.[Crossref]
  43. Cullen KA, Mace KE, Arguin PM, , 2016. Malaria surveillance - United States, 2013. MMWR Surveillance Summary 65: 112.[Crossref]

Data & Media loading...

  • Received : 22 Feb 2016
  • Accepted : 16 Apr 2016

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error