Chapter 15 : Malaria

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Malaria, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815486/9781555814304_Chap15-1.gif /docserver/preview/fulltext/10.1128/9781555815486/9781555814304_Chap15-2.gif


Malaria is classically known as a disease of fever, anemia, and splenomegaly, with clinical descriptions dating back 6,000 years. The parasites are entirely confined to the bloodstream, bone marrow, and spleen. The genome of the most lethal human species, , along with that of murine malaria , was completed initially. Chronic parasitemia causes chronic sequelae or permanently selects for genetic disorders which protect from severe malaria disease but cause other human disease, such as sickle cell anemia. , in addition to the classic triad of fever, anemia, and spenomegaly, can cause reversible dysfunction of almost any organ, unless malaria progresses to death. The human parasites increase destruction and decrease production of erythrocytes. The pathogenesis of cerebral malaria is multi-factorial and begins with sequestration of parasitized erythrocytes to brain endothelial cells in postcapillary venules. Chronic malaria antigen stimulation of the immune system by persistent parasitemia has been associated with oncogenic translocation by Epstein-Barr virus (EBV) to produce Burkitt’s lymphoma. The quinolines target hemozoin formation in the lipid environment of the acidic digestive vacuole and therefore are stage specific to the erythrocyte stages rather than to the gametocyte or liver stages. Acute malaria is entirely preventable and can be completely curable in settings with rapid accurate diagnosis and effective chemotherapy.

Citation: Sullivan, Jr. D, Gandhi N. 2009. Malaria, p 259-274. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch15
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Surface changes of infected trophozoite-stage erythrocyte. The normal erythrocyte (left) has a smooth surface and minimizes its volume with the biconcave disc. In contrast, the infected trophozoite-stage erythrocyte has been transformed to contain knobs which act as ligands to host receptors on endothelial cells or leukocytes.

Citation: Sullivan, Jr. D, Gandhi N. 2009. Malaria, p 259-274. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Malaria fever curves. Typical fever curves from patients with or tertian malaria (A), or quotidian malaria (B), and quartan malaria (C), with temperatures every 48, 24 and 72 h.

Citation: Sullivan, Jr. D, Gandhi N. 2009. Malaria, p 259-274. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

Imported malaria cases in the United States and the United Kingdom from 1966 to 2005. Total number of malaria cases from the United Kingdom (filled triangles) and the United States (filled squares) and total deaths in the United Kingdom (empty triangles) and the United States (empty squares). In the United States, total civilian cases (filled circles) outnumber military cases (empty circles) almost 10-fold.

Citation: Sullivan, Jr. D, Gandhi N. 2009. Malaria, p 259-274. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4.
Figure 4.

Onset of malaria case presentation, 1992 to 2005. The time to clinical presentation in months after travel by species, with (solid bar), (hatched bar), (stippled bar), and (vertical bar). Values are averages of 12 years with standard deviations of the means.

Citation: Sullivan, Jr. D, Gandhi N. 2009. Malaria, p 259-274. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5.
Figure 5.

Age-dependent prevalence of severe malaria and deaths. (A) Increasing how often the mosquitoes deliver an infectious bite or the entomologic inoculation rate determines an age-dependent pattern for severe disease, anemia, cerebral malaria, or renal disease, varying from holoendemic (parasite prevalence greater than 60 to 70%), hyperendemic (parasite prevalence between 50 to 70%), mesoendemic (parasite prevalence between 20 and 50%), and hypoendemic (parasite prevalence less than 10%) forms of malaria. The entomologic inoculation rate can vary from 1 to over 1,000 each year. (B) Peak prevalence in a region where malaria is holoendemic follows by a few years the peak risk period for deaths, which is under age 5.

Citation: Sullivan, Jr. D, Gandhi N. 2009. Malaria, p 259-274. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Agarwal, A.,, A. Guindo,, Y. Cissoko,, J. G. Taylor,, D. Coulibaly,, A. Kone,, K. Kayentao,, A. Djimde,, C. V. Plowe,, O. Doumbo,, T. E. Wellems, and, D. Diallo. 2000. Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood 96: 23582363.
2. Akide-Ndunge, O. B.,, K. Ayi, and, P. Arese. 2003. The Haldane malaria hypothesis: facts, artifacts, and a prophecy. Redox. Rep. 8: 311316.
3. Allison, A. C. 1954. Protection afforded by sickle-cell trait against subtertian malareal infection. Br. Med. J. 1: 290294.
4. Arie, T.,, R. M. Fairhurst,, N. J. Brittain,, T. E. Wellems, and, J. A. Dvorak. 2005. Hemoglobin C modulates the surface topography of Plasmodium falciparum-infected erythrocytes. J. Struct. Biol. 150: 163169.
5. Bannister, L. H.,, J. M. Hopkins,, R. E. Fowler,, S. Krishna, and, G. H. Mitchell. 2000. A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages. Parasitol. Today 16: 427433.
6. Beet, E. A. 1949. The genetics of the sickle-cell trait in a Bantu tribe. Ann. Eugen. 14: 279284.
7. Beutler, E.,, and S. Duparc. 2007. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am. J. Trop. Med. Hyg. 77: 779789.
8. Bottieau, E.,, J. Clerinx,, E. Van Den Enden,, M. Van Esbroeck,, R. Colebunders,, A. Van Gompel, and, J. Van Den Ende. 2006. Imported non- Plasmodium falciparum malaria: a five-year prospective study in a European referral center. Am. J. Trop. Med. Hyg. 75: 133138.
9. Brady, G.,, G. J. MacArthur, and, P. J. Farrell. 2007. Epstein-Barr virus and Burkitt lymphoma. J. Clin. Pathol. 60: 13971402.
10. Bray, P. G.,, S. A. Ward, and, P. M. O’Neill. 2005. Quinolines and artemisinin: chemistry, biology and history. Curr. Top. Microbiol. Immunol. 295: 3338.
11. Breman, J. G.,, M. S. Alilio, and, A. Mills. 2004. Conquering the intolerable burden of malaria: what’s new, what’s needed: a summary. Am. J. Trop. Med. Hyg. 71: 115.
12. Brent, A. J.,, J. O. Oundo,, I. Mwangi,, L. Ochola,, B. Lowe, and, J. A. Berkley. 2006. Salmonella bacteremia in Kenyan children. Pediatr. Infect. Dis. J. 25: 230236.
13. Bronzan, R. N.,, T. E. Taylor,, J. Mwenechanya,, M. Tembo,, K. Kayira,, L. Bwanaisa,, A. Njobvu,, W. Kondowe,, C. Chalira,, A. L. Walsh,, A. Phiri,, L. K. Wilson,, M. E. Molyneux, and, S. M. Graham. 2007. Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. J. Infect. Dis. 195: 895904.
14. Burkitt, D. P. 1971. Epidemiology of Burkitt’s lymphoma. Proc. R. Soc. Med. 64: 909910.
15. Burkitt, D. P. 1969. Etiology of Burkitt’s lymphoma--an alternative hypothesis to a vectored virus. J. Natl. Cancer Inst. 42: 1928.
16. Carlton, J. M.,, S. V. Angiuoli,, B. B. Suh,, T. W. Kooij,, M. Pertea,, J. C. Silva,, M. D. Ermolaeva,, J. E. Allen,, J. D. Selengut,, H. L. Koo,, J. D. Peterson,, M. Pop,, D. S. Kosack,, M. F. Shumway,, S. L. Bidwell,, S. J. Shallom,, S. E. van Aken,, S. B. Riedmuller,, T. V. Feldblyum,, J. K. Cho,, J. Quackenbush,, M. Sedegah,, A. Shoaibi,, L. M. Cummings,, L. Florens,, J. R. Yates,, J. D. Raine,, R. E. Sinden,, M. A. Harris,, D. A. Cunningham,, P. R. Preiser,, L. W. Bergman,, A. B. Vaidya,, L. H. van Lin,, C. J. Janse,, A. P. Waters,, H. O. Smith,, O. R. White,, S. L. Salzberg,, J. C. Venter,, C. M. Fraser,, S. L. Hoffman,, M. J. Gardner, and, D. J. Carucci. 2002. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature 419: 512519.
17. Carpenter, L. M.,, R. Newton,, D. Casabonne,, J. Ziegler,, S. Mbulaiteye,, E. Mbidde,, H. Wabinga,, H. Jaffe, and, V. Beral. 2008. Antibodies against malaria and Epstein-Barr virus in childhood Burkitt lymphoma: a case-control study in Uganda. Int. J. Cancer 122: 13191323.
18. Carter, J. A.,, B. G. Neville,, S. White,, A. J. Ross,, G. Otieno,, N. Mturi,, C. Musumba, and, C. R. Newton. 2004. Increased prevalence of epilepsy associated with severe falciparum malaria in children. Epilepsia 45: 978981.
19. Carter, R.,, K. N. Mendis, and, D. Roberts. 2000. Spatial targeting of interventions against malaria. Bull. W. H. O. 78: 14011411.
20. Casals-Pascual, C.,, O. Kai,, J. O. Cheung,, S. Williams,, B. Lowe,, M. Nyanoti,, T. N. Williams,, K. Maitland,, M. Molyneux,, C. R. Newton,, N. Peshu,, S. M. Watt, and, D. J. Roberts. 2006. Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo. Blood 108: 25692577.
21. Chen, Q.,, M. Schlichtherle, and, M. Wahlgren. 2000. Molecular aspects of severe malaria. Clin. Microbiol. Rev. 13: 439450.
22. Chene, A.,, D. Donati,, A. O. Guerreiro-Cacais,, V. Levitsky,, Q. Chen,, K. I. Falk,, J. Orem,, F. Kironde,, M. Wahlgren, and, M. T. Bejarano. 2007. A molecular link between malaria and Epstein-Barr virus reactivation. PLoS Pathog. 3: e80.
23. Cholera, R.,, N. J. Brittain,, M. R. Gillrie,, T. M. Lopera-Mesa,, S. A. Diakite,, T. Arie,, M. A. Krause,, A. Guindo,, A. Tubman,, H. Fujioka,, D. A. Diallo,, O. K. Doumbo,, M. Ho,, T. E. Wellems, and, R. M. Fairhurst. 2008. Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc. Natl. Acad. Sci. USA 105: 991996.
24. Clark, I. A.,, and W. B. Cowden. 2003. The pathophysiology of falciparum malaria. Pharmacol. Ther. 99: 221.
25. Collins, W. E.,, and G. M. Jeffery. 2007. Plasmodium malariae: parasite and disease. Clin. Microbiol. Rev. 20: 579592.
26. Cordoliani, Y. S.,, J. L. Sarrazin,, D. Felten,, E. Caumes,, C. Leveque, and, A. Fisch. 1998. MR of cerebral malaria. AJNR Am. J. Neuroradiol. 19: 871874.
27. Cox-Singh, J.,, T. M. Davis,, K. S. Lee,, S. S. Shamsul,, A. Matusop,, S. Ratnam,, H. A. Rahman,, D. J. Conway, and, B. Singh. 2008. Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin. Infect. Dis. 46: 165171.
28. Cox-Singh, J.,, and B. Singh. 2008. Knowlesi malaria: newly emergent and of public health importance? Trends Parasitol. 24: 406410.
29. Cranfield, M. R.,, T. K. Graczyk,, F. B. Beall,, D. M. Ialeggio,, M. L. Shaw, and, M. L. Skjoldager. 1994. Subclinical avian malaria infections in African black-footed penguins ( Spheniscus demersus) and induction of parasite recrudescence. J. Wildl. Dis. 30: 372376.
30. Curtis, C. F.,, C. A. Maxwell,, S. M. Magesa,, R. T. Rwegoshora, and, T. J. Wilkes. 2006. Insecticide-treated bed-nets for malaria mosquito control. J. Am. Mosq. Control Assoc. 22: 501506.
31. Desakorn, V.,, A. M. Dondorp,, K. Silamut,, W. Pongtavornpinyo,, D. Sahassananda,, K. Chotivanich,, P. Pitisuttithum,, A. M. Smithyman,, N. P. Day, and, N. J. White. 2005. Stagedependent production and release of histidine-rich protein 2 by Plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 99: 517524.
32. Dobbie, M.,, J. Crawley,, C. Waruiru,, K. Marsh, and, R. Surtees. 2000. Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism? Am. J. Trop. Med. Hyg. 62: 284290.
33. Dondorp, A. M.,, V. Desakorn,, W. Pongtavornpinyo,, D. Sahassananda,, K. Silamut,, K. Chotivanich,, P. N. Newton,, P. Pitisuttithum,, A. M. Smithyman,, N. J. White, and, N. P. Day. 2005. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med. 2: e204.
34. Dondorp, A. M.,, S. J. Lee,, M. A. Faiz,, S. Mishra,, R. Price,, E. Tjitra,, M. Than,, Y. Htut,, S. Mohanty,, E. B. Yunus,, R. Rahman,, F. Nosten,, N. M. Anstey,, N. P. Day, and, N. J. White. 2008. The relationship between age and the manifestations of and mortality associated with severe malaria. Clin. Infect. Dis. 47: 151157.
35. Duarte, M. I.,, C. E. Corbett,, M. Boulos, and, V. Amato Neto. 1985. Ultrastructure of the lung in falciparum malaria. Am. J. Trop. Med. Hyg. 34: 3135.
36. Duffy, P. E.,, and M. Fried. 2005. Malaria in the pregnant woman. Curr. Top. Microbiol. Immunol. 295: 169200.
37. Dugbartey, A. T.,, M. T. Dugbartey, and, M. Y. Apedo. 1998. Delayed neuropsychiatric effects of malaria in Ghana. J. Nerv. Ment. Dis. 186: 183186.
38. Eckstein-Ludwig, U.,, R. J. Webb,, I. D. Van Goethem,, J. M. East,, A. G. Lee,, M. Kimura,, P. M. O’Neill,, P. G. Bray,, S. A. Ward, and, S. Krishna. 2003. Artemisinins target the SERCA of Plasmodium falciparum. Nature 424: 957961.
39. Fairhurst, R. M.,, D. I. Baruch,, N. J. Brittain,, G. R. Ostera,, J. S. Wallach,, H. L. Hoang,, K. Hayton,, A. Guindo,, M. O. Makobongo,, O. M. Schwartz,, A. Tounkara,, O. K. Doumbo,, D. A. Diallo,, H. Fujioka,, M. Ho, and, T. E. Wellems. 2005. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature 435: 11171121.
40. Foth, B. J.,, and G. I. McFadden. 2003. The apicoplast: a plastid in Plasmodium falciparum and other Apicomplexan parasites. Int. Rev. Cytol. 224: 57110.
41. Fradin, M. S.,, and J. F. Day. 2002. Comparative efficacy of insect repellents against mosquito bites. N. Engl. J. Med. 347: 1318.
42. Francis, S. E.,, D. J. Sullivan, Jr., and, D. E. Goldberg. 1997. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu. Rev. Microbiol. 51: 97123.
43. Gamanagatti, S.,, and H. Kandpal. 2006. MR imaging of cerebral malaria in a child. Eur. J. Radiol. 60: 4647.
44. Gardner, M. J.,, N. Hall,, E. Fung,, O. White,, M. Berriman,, R. W. Hyman,, J. M. Carlton,, A. Pain,, K. E. Nelson,, S. Bowman,, I. T. Paulsen,, K. James,, J. A. Eisen,, K. Rutherford,, S. L. Salzberg,, A. Craig,, S. Kyes,, M. S. Chan,, V. Nene,, S. J. Shallom,, B. Suh,, J. Peterson,, S. Angiuoli,, M. Pertea,, J. Allen,, J. Selengut,, D. Haft,, M. W. Mather,, A. B. Vaidya,, D. M. Martin,, A. H. Fairlamb,, M. J. Fraunholz,, D. S. Roos,, S. A. Ralph,, G. I. McFadden,, L. M. Cummings,, G. M. Subramanian,, C. Mungall,, J. C. Venter,, D. J. Carucci,, S. L. Hoffman,, C. Newbold,, R. W. Davis,, C. M. Fraser, and, B. Barrell. 2002. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419: 498511.
45. Gluzman, I. Y.,, S. E. Francis,, A. Oksman,, C. E. Smith,, K. L. Duffin, and, D. E. Goldberg. 1994. Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway. J. Clin. Investig. 93: 16021608.
46. Grobusch, M. P.,, and P. G. Kremsner. 2005. Uncomplicated malaria. Curr. Top. Microbiol. Immunol. 295: 83104.
47. Guerra, C. A.,, P. W. Gikandi,, A. J. Tatem,, A. M. Noor,, D. L. Smith,, S. I. Hay, and, R. W. Snow. 2008. The limits and intensity of Plasmodium falciparum transmission: implications for malaria control and elimination worldwide. PLoS Med. 5: e38.
48. Guerra, C. A.,, S. I. Hay,, L. S. Lucioparedes,, P. W. Gikandi,, A. J. Tatem,, A. M. Noor, and, R. W. Snow. 2007. Assembling a global database of malaria parasite prevalence for the Malaria Atlas Project. Malar. J. 6: 17.
49. Guerra, C. A.,, R. W. Snow, and, S. I. Hay. 2006. Mapping the global extent of malaria in 2005. Trends Parasitol. 22: 353358.
50. Haldar, K.,, S. C. Murphy,, D. A. Milner, and, T. E. Taylor. 2007. Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease. Annu. Rev. Pathol. 2: 217249.
51. Harpending, H.,, and G. Cochran. 2006. Genetic diversity and genetic burden in humans. Infect. Genet. Evol. 6: 154162.
52. Hay, S. I.,, and R. W. Snow. 2006. The Malaria Atlas Project: developing global maps of malaria risk. PLoS Med. 3: e473.
53. Hill, D. R.,, J. K. Baird,, M. E. Parise,, L. S. Lewis,, E. T. Ryan, and, A. J. Magill. 2006. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am. J. Trop. Med. Hyg. 75: 402415.
54. Hill, J.,, J. Lines, and, M. Rowland. 2006. Insecticide-treated nets. Adv. Parasitol. 61: 77128.
55. Hsu, E. 2006. Reflections on the ‘discovery’ of the antimalarial qinghao. Br. J. Clin. Pharmacol. 61: 666670.
56. Hunt, P.,, A. Afonso,, A. Creasey,, R. Culleton,, A. B. Sidhu,, J. Logan,, S. G. Valderramos,, I. McNae,, S. Cheesman,, V. do Rosario,, R. Carter,, D. A. Fidock, and, P. Cravo. 2007. Gene encoding a deubiquitinating enzyme is mutated in artesu-nate- and chloroquine-resistant rodent malaria parasites. Mol. Microbiol. 65: 2740.
57. Idro, R. 2003. Severe anaemia in childhood cerebral malaria is associated with profound coma. Afr. Health Sci. 3: 1518.
58. Idro, R.,, J. A. Carter,, G. Fegan,, B. G. Neville, and, C. R. Newton. 2006. Risk factors for persisting neurological and cognitive impairments following cerebral malaria. Arch. Dis. Child. 91: 142148.
59. Idro, R.,, N. E. Jenkins, and, C. R. Newton. 2005. Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol. 4: 827840.
60. John, C. C.,, A. Panoskaltsis-Mortari,, R. O. Opoka,, G. S. Park,, P. J. Orchard,, A. M. Jurek,, R. Idro,, J. Byarugaba, and, M. J. Boivin. 2008. Cerebrospinal fluid cytokine levels and cognitive impairment in cerebral malaria. Am. J. Trop. Med. Hyg. 78: 198205.
61. Jonsson, B.,, A. Nyberg, and, C. Henning. 1993. Theoretical aspects of detection of bacteraemia as a function of the volume of blood cultured. APMIS 101: 595601.
62. Joshi, R.,, J. M. Colford, Jr.,, A. L. Reingold, and, S. Kalantri. 2008. Nonmalarial acute undifferentiated fever in a rural hospital in central India: diagnostic uncertainty and over-treatment with antimalarial agents. Am. J. Trop. Med. Hyg. 78: 393399.
63. Kantele, A.,, H. Marti,, I. Felger,, D. Muller, and, T. S. Jokiranta. 2008. Monkey malaria in a European traveler returning from Malaysia. Emerg. Infect. Dis. 14: 14341436.
64. Kaushik, A.,, V. K. Sharma,, Sadhna, R. Kumar, and, R. Mitra. 1992. Malarial placental infection and low birth weight babies. Mater. Med. Pol. 24: 109110.
65. Kelly, G. L.,, and A. B. Rickinson. 2007. Burkitt lymphoma: revisiting the pathogenesis of a virus-associated malignancy. Hematology Am. Soc. Hematol. Educ. Program 2007: 277284.
66. Kennan, R. P.,, F. S. Machado,, S. C. Lee,, M. S. Desruisseaux,, M. Wittner,, M. Tsuji, and, H. B. Tanowitz. 2005. Reduced cerebral blood flow and N-acetyl aspartate in a murine model of cerebral malaria. Parasitol. Res. 96: 302307.
67. Kim, K.,, and L. M. Weiss. 2004. Toxoplasma gondii: the model apicomplexan. Int. J. Parasitol. 34: 423432.
68. Kochar, D. K.,, P. Singh,, P. Agarwal,, S. K. Kochar,, R. Pokharna, and, P. K. Sareen. 2003. Malarial hepatitis. J. Assoc. Physicians India 51: 10691072.
69. Lobo, C. A.,, and N. Kumar. 1998. Sexual differentiation and development in the malaria parasite. Parasitol. Today 14: 146150.
70. Looareesuwan, S.,, P. Wilairatana,, S. Krishna,, B. Kendall,, S. Vannaphan,, C. Viravan, and, N. J. White. 1995. Magnetic resonance imaging of the brain in patients with cerebral malaria. Clin. Infect. Dis. 21: 300309.
71. Lubitz, J. M. 1949. Pathology of the ruptured spleen in acute vivax malaria. Blood 4: 11681176.
72. Marshall, J. C.,, P. M. Walker,, D. M. Foster,, D. Harris,, M. Ribeiro,, J. Paice,, A. D. Romaschin, and, A. N. Derzko. 2002. Measurement of endotoxin activity in critically ill patients using whole blood neutrophil dependent chemiluminescence. Crit. Care 6: 342348.
73. Massey, J. G.,, T. K. Graczyk, and, M. R. Cranfield. 1996. Characteristics of naturally acquired Plasmodium relictum capistranoae infections in naive Hawaiian crows ( Corvus hawaiiensis) in Hawaii. J. Parasitol. 82: 182185.
74. Medana, I. M.,, G. Chaudhri,, T. Chan-Ling, and, N. H. Hunt. 2001. Central nervous system in cerebral malaria: ‘innocent bystander’ or active participant in the induction of immunopathology? Immunol. Cell Biol. 79: 101120.
75. Medana, I. M.,, N. P. Day,, T. T. Hien,, N. T. Mai,, D. Bethell,, N. H. Phu,, J. Farrar,, M. M. Esiri,, N. J. White, and, G. D. Turner. 2002. Axonal injury in cerebral malaria. Am. J. Pathol. 160: 655666.
76. Medana, I. M.,, T. T. Hien,, N. P. Day,, N. H. Phu,, N. T. Mai,, L. V. Chu’ong,, T. T. Chau,, A. Taylor,, H. Salahifar,, R. Stocker,, G. Smythe,, G. D. Turner,, J. Farrar,, N. J. White, and, N. H. Hunt. 2002. The clinical significance of cerebrospinal fluid levels of kynurenine pathway metabolites and lactate in severe malaria. J. Infect. Dis. 185: 650656.
77. Miller, L. H.,, D. I. Baruch,, K. Marsh, and, O. K. Doumbo. 2002. The pathogenic basis of malaria. Nature 415: 673679.
78. Mishra, S. K.,, K. Dietz,, S. Mohanty, and, S. S. Pati. 2007. Influence of acute renal failure in patients with cerebral malaria - a hospital-based study from India. Trop. Doct. 37: 1031010314.
79. Moody, A. 2002. Rapid diagnostic tests for malaria parasites. Clin. Microbiol. Rev. 15: 6678.
80. Moormann, A. M.,, K. Chelimo,, O. P. Sumba,, M. L. Lutzke,, R. Ploutz-Snyder,, D. Newton,, J. Kazura, and, R. Rochford. 2005. Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children. J. Infect. Dis. 191: 12331238.
81. Moormann, A. M.,, A. D. Sullivan,, R. A. Rochford,, S. W. Chensue,, P. J. Bock,, T. Nyirenda, and, S. R. Meshnick. 1999. Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation. J. Infect. Dis. 180: 19871993.
82. Mung’Ala-Odera, V.,, R. W. Snow, and, C. R. Newton. 2004. The burden of the neurocognitive impairment associated with Plasmodium falciparum malaria in sub-Saharan Africa. Am. J. Trop. Med. Hyg. 71: 6470.
83. Newbold, C. I.,, A. G. Craig,, S. Kyes,, A. R. Berendt,, R. W. Snow,, N. Peshu, and, K. Marsh. 1997. PfEMP1, polymorphism and pathogenesis. Ann. Trop. Med. Parasitol. 91: 551557.
84. Ngoungou, E. B.,, J. Koko,, M. Druet-Cabanac,, Y. Assen-gone-Zeh-Nguema,, M. N. Launay,, E. Engohang,, M. Moubeka-Mounguengui,, P. Kouna-Ndouongo,, P. M. Loembe,, P. M. Preux, and, M. Kombila. 2006. Cerebral malaria and sequelar epilepsy: first matched case-control study in Gabon. Epilepsia 47: 21472153.
85. Noland, G. S.,, N. Briones, and, D. J. Sullivan, Jr. 2003. The shape and size of hemozoin crystals distinguishes diverse Plasmodium species. Mol. Biochem. Parasitol. 130: 9199.
86. O’Neill, P. M.,, and G. H. Posner. 2004. A medicinal chemistry perspective on artemisinin and related endoperoxides. J. Med. Chem. 47: 29452964.
87. O’Neill, P. M.,, S. L. Rawe,, K. Borstnik,, A. Miller,, S. A. Ward,, P. G. Bray,, J. Davies,, C. H. Oh, and, G. H. Posner. 2005. Enantiomeric 1,2,4-trioxanes display equivalent in vitro antimalarial activity versus Plasmodium falciparum malaria parasites: implications for the molecular mechanism of action of the artemisinins. Chembiochem 6: 20482054.
88. Oh, S. S.,, and A. H. Chishti. 2005. Host receptors in malaria merozoite invasion. Curr. Top. Microbiol. Immunol. 295: 203232.
89. Olliaro, P. L.,, and W. R. Taylor. 2004. Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: a review. J. Postgrad. Med. 50: 4044.
90. Omodeo-Sale, F.,, A. Motti,, A. Dondorp,, N. J. White, and, D. Taramelli. 2005. Destabilisation and subsequent lysis of human erythrocytes induced by Plasmodium falciparum haem products. Eur. J. Haematol. 74: 324332.
91. Pagola, S.,, P. W. Stephens,, D. S. Bohle,, A. D. Kosar, and, S. K. Madsen. 2000. The structure of malaria pigment betahaematin. Nature 404: 307310.
92. Parekh, S. B.,, W. A. Bubb,, N. H. Hunt, and, C. Rae. 2006. Brain metabolic markers reflect susceptibility status in cytokine gene knockout mice with murine cerebral malaria. Int. J. Parasitol. 36: 14091418.
93. Penet, M. F.,, F. Kober,, S. Confort-Gouny,, Y. Le Fur,, C. Dalmasso,, N. Coltel,, A. Liprandi,, J. M. Gulian,, G. E. Grau,, P. J. Cozzone, and, A. Viola. 2007. Magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with Plasmodium berghei ANKA. J. Biol. Chem. 282: 1450514514.
94. Perkins, D. J.,, J. B. Hittner,, E. D. Mwaikambo,, D. L. Granger,, J. B. Weinberg, and, N. M. Anstey. 2005. Impaired systemic production of prostaglandin E2 in children with cerebral malaria. J. Infect. Dis. 191: 15481557.
95. Pisciotta, J. M.,, and D. Sullivan. 2008. Hemozoin: oil versus water. Parasitol. Int. 57: 8996.
96. Planche, T.,, A. Dzeing,, E. Ngou-Milama,, M. Kombila, and, P. W. Stacpoole. 2005. Metabolic complications of severe malaria. Curr. Top. Microbiol. Immunol. 295: 105136.
97. Pollack, R. J.,, A. E. Kiszewski, and, A. Spielman. 2002. Repelling mosquitoes. N. Engl. J. Med. 347: 23.
98. Pongponratn, E.,, G. D. Turner,, N. P. Day,, N. H. Phu,, J. A. Simpson,, K. Stepniewska,, N. T. Mai,, P. Viriyavejakul,, S. Looareesuwan,, T. T. Hien,, D. J. Ferguson, and, N. J. White. 2003. An ultrastructural study of the brain in fatal Plasmodium falciparum malaria. Am. J. Trop. Med. Hyg. 69: 345359.
99. Posner, G. P.,, and S. R. Meshnick. 2001. Radical mechanism of action of the artemisinin-type compounds. Trends Parasitol. 17: 266268.
100. Prudencio, M.,, A. Rodriguez, and, M. M. Mota. 2006. The silent path to thousands of merozoites: the Plasmodium liver stage. Nat. Rev. Microbiol. 4: 849856.
101. Rainey, J. J.,, W. O. Mwanda,, P. Wairiumu,, A. M. Moormann,, M. L. Wilson, and, R. Rochford. 2007. Spatial distribution of Burkitt’s lymphoma in Kenya and association with malaria risk. Trop. Med. Int. Health. 12: 936943.
102. Reisinger, E. C.,, C. Fritzsche,, R. Krause, and, G. J. Krejs. 2005. Diarrhea caused by primarily non-gastrointestinal infections. Nat. Clin. Pract. Gastroenterol. Hepatol. 2: 216222.
103. Riehle, M. A.,, P. Srinivasan,, C. K. Moreira, and, M. Jacobs-Lorena. 2003. Towards genetic manipulation of wild mosquito populations to combat malaria: advances and challenges. J. Exp. Biol. 206: 38093816.
104. Roberts, D. J.,, C. Casals-Pascual, and, D. J. Weatherall. 2005. The clinical and pathophysiological features of malarial anaemia. Curr. Top. Microbiol. Immunol. 295: 137167.
105. Sabeti, P. C.,, D. E. Reich,, J. M. Higgins,, H. Z. Levine,, D. J. Richter,, S. F. Schaffner,, S. B. Gabriel,, J. V. Platko,, N. J. Patterson,, G. J. McDonald,, H. C. Ackerman,, S. J. Campbell,, D. Altshuler,, R. Cooper,, D. Kwiatkowski,, R. Ward, and, E. S. Lander. 2002. Detecting recent positive selection in the human genome from haplotype structure. Nature 419: 832837.
106. Scholl, P. F.,, A. K. Tripathi, and, D. J. Sullivan. 2005. Bioavailable iron and heme metabolism in Plasmodium falciparum. Curr. Top. Microbiol. Immunol. 295: 293324.
107. Schwartz, E.,, M. Parise,, P. Kozarsky, and, M. Cetron. 2003. Delayed onset of malaria--implications for chemoprophylaxis in travelers. N. Engl. J. Med. 349: 15101516.
108. Shear, H. L.,, L. Grinberg,, J. Gilman,, M. E. Fabry,, G. Stamatoyannopoulos,, D. E. Goldberg, and, R. L. Nagel. 1998. Transgenic mice expressing human fetal globin are protected from malaria by a novel mechanism. Blood 92: 25202526.
109. Shiff, C. 2002. Integrated approach to malaria control. Clin. Microbiol. Rev. 15: 278293.
110. Skorokhod, A.,, E. Schwarzer,, G. Gremo, and, P. Arese. 2007. HNE produced by the malaria parasite Plasmodium falciparum generates HNE-protein adducts and decreases erythrocyte deformability. Redox Rep. 12: 7375.
111. Smith, D. L.,, J. Dushoff,, R. W. Snow, and, S. I. Hay. 2005. The entomological inoculation rate and Plasmodium falciparum infection in African children. Nature 438: 492495.
112. Smith, D. L.,, C. A. Guerra,, R. W. Snow, and, S. I. Hay. 2007. Standardizing estimates of the Plasmodium falciparum parasite rate. Malar. J. 6: 131.
113. Smith, D. L.,, F. E. McKenzie,, R. W. Snow, and, S. I. Hay. 2007. Revisiting the basic reproductive number for malaria and its implications for malaria control. PLoS Biol. 5: e42.
114. Smith, J. D.,, and A. G. Craig. 2005. The surface of the Plasmodium falciparum-infected erythrocyte. Curr. Issues Mol. Biol. 7: 8193.
115. Smith, J. D.,, A. G. Craig,, N. Kriek,, D. Hudson-Taylor,, S. Kyes,, T. Fagan,, R. Pinches,, D. I. Baruch,, C. I. Newbold, and, L. H. Miller. 2000. Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proc. Natl. Acad. Sci. USA 97: 17661771.
116. Snow, R. W.,, M. Craig,, U. Deichmann, and, K. Marsh. 1999. Estimating mortality, morbidity and disability due to malaria among Africa’s non-pregnant population. Bull. W. H. O. 77: 624640.
117. Snow, R. W.,, E. L. Korenromp, and, E. Gouws. 2004. Pediatric mortality in Africa: Plasmodium falciparum malaria as a cause or risk? Am. J. Trop. Med. Hyg. 71: 1624.
118. Sowunmi, A.,, O. A. Ogundahunsi,, C. O. Falade,, G. O. Gbotosho, and, A. M. Oduola. 2000. Gastrointestinal manifestations of acute falciparum malaria in children. Acta Trop. 74: 7376.
119. Spencer, K. A.,, K. L. Buchanan,, S. Leitner,, A. R. Goldsmith, and, C. K. Catchpole. 2005. Parasites affect song complexity and neural development in a songbird. Proc. Biol. Sci. 272: 20372043.
120. Srivastava, K.,, I. A. Cockburn,, A. Swaim,, L. E. Thompson,, A. Tripathi,, C. A. Fletcher,, E. M. Shirk,, H. Sun,, M. A. Kowalska,, K. Fox-Talbot,, D. Sullivan,, F. Zavala, and, C. N. Morrell. 2008. Platelet factor 4 mediates inflammation in experimental cerebral malaria. Cell. Host Microbe 4: 179187.
121. Steketee, R. W.,, B. L. Nahlen,, M. E. Parise, and, C. Menendez. 2001. The burden of malaria in pregnancy in malaria-endemic areas. Am. J. Trop. Med. Hyg. 64: 2835.
122. Stephenson, I.,, J. Roper,, M. Fraser,, K. Nicholson, and, M. Wiselka. 2003. Dengue fever in febrile returning travellers to a UK regional infectious diseases unit. Travel Med. Infect. Dis. 1: 8993.
123. Su, X. Z.,, V. M. Heatwole,, S. P. Wertheimer,, F. Guinet,, J. A. Herrfeldt,, D. S. Peterson,, J. A. Ravetch, and, T. E. Wellems. 1995. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82: 89100.
124. Sullivan, D. J. 2002. Theories on malarial pigment formation and quinoline action. Int. J. Parasitol. 32: 16451653.
125. Telford, S. R., Jr. 1977. The distribution, incidence and general ecology of saurian malaria in Middle America. Int. J. Parasitol. 7: 299314.
126. Telford, S. R., Jr. 1986. Studies on African saurian malarias: Plasmodium holaspi n. sp. from the flying lacertid Holaspis guentheri. J. Parasitol. 72: 271275.
127. Vaidya, A. B. 2004. Mitochondrial and plastid functions as antimalarial drug targets. Curr. Drug Targets Infect. Disord. 4: 1123.
128. Vaidya, A. B.,, and M. W. Mather. 2005. A post-genomic view of the mitochondrion in malaria parasites. Curr. Top. Microbiol. Immunol. 295: 233250.
129. Varney, N. R.,, R. J. Roberts,, J. A. Springer,, S. K. Connell, and, P. S. Wood. 1997. Neuropsychiatric sequelae of cerebral malaria in Vietnam veterans. J. Nerv. Ment. Dis. 185: 695703.
130. Venet, C.,, F. Zeni,, A. Viallon,, A. Ross,, P. Pain,, P. Gery,, D. Page,, R. Vermesch,, M. Bertrand,, F. Rancon, and, J. C. Bertrand. 2000. Endotoxaemia in patients with severe sepsis or septic shock. Intensive Care Med. 26: 538544.
131. Viebig, N. K.,, E. Levin,, S. Dechavanne,, S. J. Rogerson,, J. Gysin,, J. D. Smith,, A. Scherf, and, B. Gamain. 2007. Disruption of var2csa gene impairs placental malaria associated adhesion phenotype. PLoS ONE 2: e910.
132. Vinetz, J. M.,, J. Li,, T. F. McCutchan, and, D. C. Kaslow. 1998. Plasmodium malariae infection in an asymptomatic 74-year-old Greek woman with splenomegaly. N. Engl. J. Med. 338: 367371.
133. Vlachou, D.,, T. Schlegelmilch,, E. Runn,, A. Mendes, and, F. C. Kafatos. 2006. The developmental migration of Plasmodium in mosquitoes. Curr. Opin. Genet. Dev. 16: 384391.
134. Volkman, S. K.,, P. C. Sabeti,, D. DeCaprio,, D. E. Neafsey,, S. F. Schaffner,, D. A. Milner, Jr.,, J. P. Daily,, O. Sarr,, D. Ndiaye,, O. Ndir,, S. Mboup,, M. T. Duraisingh,, A. Lukens,, A. Derr,, N. Stange-Thomann,, S. Waggoner,, R. Onofrio,, L. Ziaugra,, E. Mauceli,, S. Gnerre,, D. B. Jaffe,, J. Zainoun,, R. C. Wiegand,, B. W. Birren,, D. L. Hartl,, J. E. Galagan,, E. S. Lander, and, D. F. Wirth. 2007. A genome-wide map of diversity in Plasmodium falciparum. Nat. Genet. 39: 113119.
135. Vythilingam, I.,, Y. M. Noorazian,, T. C. Huat,, A. I. Jiram,, Y. M. Yusri,, A. H. Azahari,, I. Norparina,, A. Noorrain, and, S. Lokmanhakim. 2008. Plasmodium knowlesi in humans, macaques and mosquitoes in peninsular Malaysia. Parasit. Vectors 1: 26.
136. Weatherall, D. J.,, L. H. Miller,, D. I. Baruch,, K. Marsh,, O. K. Doumbo,, C. Casals-Pascual, and, D. J. Roberts. 2002. Malaria and the red cell. Hematology Am. Soc. Hematol. Educ. Program: 3557.
137. White, N. J. 2008. Plasmodium knowlesi: the fifth human malaria parasite. Clin. Infect. Dis. 46: 172173.
138. Wiersch, S. C.,, W. A. Maier, and, H. Kampen. 2005. Plasmodium (Haemamoeba) cathemerium gene sequences for phylogenetic analysis of malaria parasites. Parasitol. Res. 96: 9094.
139. Wiesner, J.,, A. Reichenberg,, S. Heinrich,, M. Schlitzer, and, H. Jomaa. 2008. The plastid-like organelle of apicomplexan parasites as drug target. Curr. Pharm. Des. 14: 855871.
140. Williams, T. N.,, T. W. Mwangi,, S. Wambua,, N. D. Alexander,, M. Kortok,, R. W. Snow, and, K. Marsh. 2005. Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases. J. Infect. Dis. 192: 178186.
141. Winstanley, P. 2001. Modern chemotherapeutic options for malaria. Lancet Infect. Dis. 1: 242250.
142. Woolhouse, M. E.,, C. Dye,, J. F. Etard,, T. Smith,, J. D. Charlwood,, G. P. Garnett,, P. Hagan,, J. L. Hii,, P. D. Ndhlovu,, R. J. Quinnell,, C. H. Watts,, S. K. Chandiwana, and, R. M. Anderson. 1997. Heterogeneities in the transmission of infectious agents: implications for the design of control programs. Proc. Natl. Acad. Sci. USA 94: 338342.
143. Wootton, J. C.,, X. Feng,, M. T. Ferdig,, R. A. Cooper,, J. Mu,, D. I. Baruch,, A. J. Magill, and, X. Z. Su. 2002. Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature 418: 320323.
144. Yadav, P.,, R. Sharma,, S. Kumar, and, U. Kumar. 2008. Magnetic resonance features of cerebral malaria. Acta Radiol. 49: 566569.
145. Zimmermann, O.,, R. de Ciman, and, U. Gross. 2005. Bacteremia among Kenyan children. N. Engl. J. Med. 352: 13791381.
146. Zingman, B. S.,, and B. L. Viner. 1993. Splenic complications in malaria: case report and review. Clin. Infect. Dis. 16: 223232.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error