1921
Volume 96, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

The serum lipid profile in malaria patients has been found to differ from that of healthy controls. We investigated serum lipid profile changes in malaria patients over time compared with patients with other febrile diseases. In total, 217 patients were included in the study (111 malaria patients and 106 symptomatic controls, defined as malaria-negative febrile patients). Serum lipid levels (mmol/L) were significantly lower in malaria patients compared with those with other febrile diseases (total cholesterol [TC] = 3.26 [standard deviation = 0.94] versus 3.97 [1.22; < 0.001]; high-density lipoprotein cholesterol [HDL-C] = 0.43 [0.47] versus 1.05 [0.67; < 0.001], low-density lipoprotein cholesterol [LDL-C] = 2.05 [0.76] versus 2.42 [0.90; < 0.001]. Triglycerides (TGs) levels were higher in malaria patients (1.81 [1.02] versus 1.11 [0.82; < 0.001]). No significant differences were found for apolipoprotein A1, apolipoprotein B, and lipoprotein(a). Cholesterol levels increased toward reference values on day 28 (TC = 3.26–3.98, < 0.001; HDL-C = 0.43–0.96, < 0.001; LDL-C = 2.05–2.60, < 0.001). TG levels decreased from 1.81 on admission to 1.76 (day 3) and 0.88 (day 28; = 0.130). Lipid profile changes were not correlated with parasitemia or histidine-rich protein 2 levels. This study confirms characteristic temporary lipid profile changes in malaria. Lipid profile changes demonstrated a good accuracy to discriminate between malaria and other febrile diseases (area under the curve = 0.80 (95% confidence interval = 0.742–0.863, < 0.001). Several plausible hypotheses exist regarding the pathophysiology of lipid profile changes in malaria. Further studies to elucidate the precise pathways may lead to improved understanding of the underlying pathophysiology.

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References

  1. Maurois P, Vernes A, Charet P, Nouvelot A, Becquet R, Giard R, , 1979. Changes in serum lipoproteins during malariatherapy with Plasmodium vivax . Ann Trop Med Parasitol 73: 491493.[Crossref] [Google Scholar]
  2. Lambrecht AJ, Snoeck J, Timmermans U, , 1978. Transient an-alpha-lipoproteinaemia in man during infection by Plasmodium vivax . Lancet 1: 1206.[Crossref] [Google Scholar]
  3. Seshadri C, Shetty BR, Gowri N, Venkataraghavan S, Chari MV, , 1981. Serum cholesterol and total lipids in Plasmodium vivax malaria: a preliminary study. Indian J Med Res 74: 513516. [Google Scholar]
  4. Chagnon A, Guiguen Y, Sutre E, , 1985. Hypocholesterolemia in malaria: an aid to diagnosis? Sem Hop 61: 20752076. [Google Scholar]
  5. Vernes A, Dei CE, Dutoit E, Maurois P, Gentilini JL, Biguet J, , 1980. Changes of serum lipoproteins during the course of human malaria (author's transl) [in French]. Pathol Biol (Paris) 28: 457460. [Google Scholar]
  6. Cuisinier-Raynal JC, Bire F, Clerc M, Bernard J, Sarrouy J, , 1990. Human malaria: dysglobulinemia-hypocholesterolemia syndrome [in French]. Med Trop (Mars) 50: 9195. [Google Scholar]
  7. Visser BJ, Wieten RW, Nagel IM, Grobusch MP, , 2013. Serum lipids and lipoproteins in malaria—a systematic review and meta-analysis. Malar J 12: 442.[Crossref] [Google Scholar]
  8. Agbedana EO, Salimonu LS, Taylor GO, Williams AI, , 1990. Studies of total and high density lipoprotein cholesterol in childhood malaria: a preliminary study. Ann Trop Med Parasitol 84: 529530.[Crossref] [Google Scholar]
  9. Selvam R, Mathews ST, , 1992. Biochemical alterations in Plasmodium vivax-infected malarial patients before and after radical treatment. Indian J Malariol 29: 103111. [Google Scholar]
  10. Kim JS, Oh JS, Chang EA, Bae SY, Nam DH, Lee CH, Yang JH, Lee CK, Lee WJ, Kim HC, Klein TA, Lim CS, Kim YK, , 2008. Alteration of platelet counts and lipid profiles after treatment of acute Plasmodium vivax . Acta Trop 106: 3943.[Crossref] [Google Scholar]
  11. Parola P, Gazin P, Patella F, Badiaga S, Delmont J, Brouqui P, , 2004. Hypertriglyceridemia as an indicator of the severity of falciparum malaria in returned travelers: a clinical retrospective study. Parasitol Res 92: 464466.[Crossref] [Google Scholar]
  12. Mesquita TC, Martin TG, Alves ER, Jr Mello MB, Nery AF, Gomes LT, Fontes CJ, , 2016. Changes in serum lipid profile in the acute and convalescent Plasmodium vivax malaria: a cohort study. Acta Trop 163: 16.[Crossref] [Google Scholar]
  13. Djoumessi S, , 1989. Serum lipids and lipoproteins during malaria infection. Pathol Biol (Paris) 37: 909911. [Google Scholar]
  14. Kittl EM, Diridl G, Lenhart V, Neuwald C, Tomasits J, Pichler H, Bauer K, , 1992. HDL cholesterol as a sensitive diagnostic parameter in malaria [in German]. Wien Klin Wochenschr 104: 2124. [Google Scholar]
  15. Blair S, Carmona J, Correa A, , 2002. Malaria in children: links between nutrition and immunity [in Spanish]. Rev Panam Salud Publica 11: 514.[Crossref] [Google Scholar]
  16. Grobusch MP, Krull M, Teichmann D, Gobels K, Suttorp N, , 2003. Falciparum malaria and Tangier disease. Int J Infect Dis 7: 7475.[Crossref] [Google Scholar]
  17. Orimadegun AE, Orimadegun BE, , 2015. Serum apolipoprotein-A1 and cholesterol levels in Nigerian children with Plasmodium falciparum infection. Med Princ Pract 24: 318324.[Crossref] [Google Scholar]
  18. Steyrer E, Durovic S, Frank S, Giessauf W, Burger A, Dieplinger H, Zechner R, Kostner GM, , 1994. The role of lecithin: cholesterol acyltransferase for lipoprotein(a) assembly. Structural integrity of low density lipoproteins is a prerequisite for Lp(a) formation in human plasma. J Clin Invest 94: 23302340.[Crossref] [Google Scholar]
  19. Nguyen TT, Ellefson RD, Hodge DO, Bailey KR, Kottke TE, Abu-Lebdeh HS, , 1997. Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women. Circulation 96: 13901397.[Crossref] [Google Scholar]
  20. Anuurad E, Rubin J, Chiem A, Tracy RP, Pearson TA, Berglund L, , 2008. High levels of inflammatory biomarkers are associated with increased allele-specific apolipoprotein(a) levels in African-Americans. J Clin Endocrinol Metab 93: 14821488.[Crossref] [Google Scholar]
  21. Kronenberg F, Utermann G, , 2013. Lipoprotein(a): resurrected by genetics. J Intern Med 273: 630.[Crossref] [Google Scholar]
  22. Bays HE, Jones PH, Orringer CE, Brown WV, Jacobson TA, , 2016. National Lipid Association annual summary of clinical lipidology 2016. J Clin Lipidol 10 (Suppl 1): S1S43.[Crossref] [Google Scholar]
  23. van Leeuwen HJ, Heezius EC, Dallinga GM, van Strijp JA, Verhoef J, van Kessel KP, , 2003. Lipoprotein metabolism in patients with severe sepsis. Crit Care Med 31: 13591366.[Crossref] [Google Scholar]
  24. Khovidhunkit W, Kim MS, Memon RA, Shigenaga JK, Moser AH, Feingold KR, Grunfeld C, , 2004. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 45: 11691196.[Crossref] [Google Scholar]
  25. Hanscheid T, Egan TJ, Grobusch MP, , 2007. Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator. Lancet Infect Dis 7: 675685.[Crossref] [Google Scholar]
  26. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, , 2007. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med 4: e296.[Crossref] [Google Scholar]
  27. World Health Organization, 2013. Management of Severe Malaria: A Practical Handbook, 3rd edition. Geneva, Switzerland: World Health Organization. [Google Scholar]
  28. Planche T, Krishna S, Kombila M, Engel K, Faucher JF, Ngou-Milama E, Kremsner PG, , 2001. Comparison of methods for the rapid laboratory assessment of children with malaria. Am J Trop Med Hyg 65: 599602. [Google Scholar]
  29. Marcovina SM, Albers JJ, Scanu AM, Kennedy H, Giaculli F, Berg K, Couderc R, Dati F, Rifai N, Sakurabayashi I, , 2000. Use of a reference material proposed by the International Federation of Clinical Chemistry and Laboratory Medicine to evaluate analytical methods for the determination of plasma lipoprotein(a). Clin Chem 46: 19561967. [Google Scholar]
  30. Arevalo-Herrera M, Lopez-Perez M, Medina L, Moreno A, Gutierrez JB, Herrera S, , 2015. Clinical profile of Plasmodium falciparum and Plasmodium vivax infections in low and unstable malaria transmission settings of Colombia. Malar J 14: 154.[Crossref] [Google Scholar]
  31. Asma UE, Taufiq F, Khan W, , 2014. Prevalence and clinical manifestations of malaria in Aligarh, India. Korean J Parasitol 52: 621629.[Crossref] [Google Scholar]
  32. Faucher JF, Ngou-Milama E, Missinou MA, Ngomo R, Kombila M, Kremsner PG, , 2002. The impact of malaria on common lipid parameters. Parasitol Res 88: 10401043.[Crossref] [Google Scholar]
  33. Davis TM, Sturm M, Zhang YR, Spencer JL, Graham RM, Li GQ, Taylor RR, , 1993. Platelet-activating factor and lipid metabolism in acute malaria. J Infect 26: 279285.[Crossref] [Google Scholar]
  34. Mohanty S, Mishra SK, Das BS, Satpathy SK, Mohanty D, Patnaik JK, Bose TK, , 1992. Altered plasma lipid pattern in falciparum malaria. Ann Trop Med Parasitol 86: 601606.[Crossref] [Google Scholar]
  35. Baptista JL, Vervoort T, Van der Stuyft P, Wery M, , 1996. Changes in plasma lipid levels as a function of Plasmodium falciparum infection in Sao Tome [in French]. Parasite 3: 335340.[Crossref] [Google Scholar]
  36. Nilsson-Ehle I, Nilsson-Ehle P, , 1990. Changes in plasma lipoproteins in acute malaria. J Intern Med 227: 151155.[Crossref] [Google Scholar]
  37. Badiaga S, Barrau K, Parola P, Brouqui P, Delmont J, , 2002. Contribution of nonspecific laboratory test to the diagnosis of malaria in febrile travelers returning from endemic areas: value of hypocholesterolemia. J Travel Med 9: 117121.[Crossref] [Google Scholar]
  38. Ngou-Milama E, Duong TH, Minko F, Dufillot D, Kombila M, Richard-Lenoble D, Mouray H, , 1995. Lipid profile during specific malaria therapy in Gabonese children [in French]. Sante 5: 9599. [Google Scholar]
  39. Onongbu IC, Onyeneke EC, , 1983. Plasma lipid changes in human malaria. Tropenmed Parasitol 34: 193196. [Google Scholar]
  40. Sumitha K, Ravichandiran K, Selvam R, , 1996. Blood lipid changes in repeated infections of vivax malaria. Indian J Malariol 33: 131138. [Google Scholar]
  41. Krishna AP, Chandrika Kumar S, Acharya M, Patil SL, , 2009. Variation in common lipid parameters in malaria infected patients. Indian J Physiol Pharmacol 53: 271274. [Google Scholar]
  42. Njoku OU, Alumanah EO, Meremikwu CU, , 2001. Effect of Azadirachta indica extract on plasma lipid levels in human malaria. Boll Chim Farm 140: 367370. [Google Scholar]
  43. Njoku OU, Ononogbu IC, Nwachukwu DE, , 1995. Plasma cholesterol, B-carotene and ascorbic acid changes in human malaria. J Commun Dis 27: 186190. [Google Scholar]
  44. Joshi G, , 2015. Neonatal malaria with hyperglycemia and hyperlipedemia: a case report. Int J Pediatr 3: 99102. [Google Scholar]
  45. Acquah S, Eghan BA, Bawa S, Boampong JN, , 2014. Differential response in lipid levels of type 2 diabetics and non-diabetic controls to falciparum malaria. Asian J Med Sci 6: 7176.[Crossref] [Google Scholar]
  46. Bouyou-Akotet M, Mawili Mboumba D, Guiyedi V, Pemba Mihindou M, Maryvonne Kombila M, , 2014. Altered total cholesterol and triglyceride levels during the course of Plasmodium falciparum infection in children. J Parasitol Vector Biol 6: 174180.[Crossref] [Google Scholar]
  47. Neves FA, Ventura AM, Filho MG, Libonati RM, , 2013. Lipid parameters in a hyperendemic area for malaria. Lipids Health Dis 12: 162.[Crossref] [Google Scholar]
  48. Chukwuocha UM, Eke KN, , 2011. Malaria parasite status and cholesterol level of malaria patients in parts of the IMO River Basin of Nigeria. Asian Pac J Trop Med 4: 993996.[Crossref] [Google Scholar]
  49. Grobusch MP, Hanscheid T, Gobels K, Slevogt H, Zoller T, Rogler G, Teichmann D, , 2003. Comparison of three antigen detection tests for diagnosis and follow-up of falciparum malaria in travellers returning to Berlin, Germany. Parasitol Res 89: 354357. [Google Scholar]
  50. Dondorp AM, Desakorn V, Pongtavornpinyo W, Sahassananda D, Silamut K, Chotivanich K, Newton PN, Pitisuttithum P, Smithyman AM, White NJ, Day NP, , 2005. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med 2: e204.[Crossref] [Google Scholar]
  51. Lee N, Baker J, Andrews KT, Gatton ML, Bell D, Cheng Q, McCarthy J, , 2006. Effect of sequence variation in Plasmodium falciparum histidine- rich protein 2 on binding of specific monoclonal antibodies: implications for rapid diagnostic tests for malaria. J Clin Microbiol 44: 27732778.[Crossref] [Google Scholar]
  52. Ghosh S, Sengupta A, Sharma S, Sonawat HM, , 2016. Early prediction of cerebral malaria by 1H NMR based metabolomics. Malar J 15: 198.[Crossref] [Google Scholar]
  53. Craig AG, Grau GE, Janse C, Kazura JW, Milner D, Barnwell JW, Turner G, Langhorne J, , 2012. The role of animal models for research on severe malaria. PLoS Pathog 8: e1002401.[Crossref] [Google Scholar]
  54. Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, Marcovina SM, Collins R, Thompson SG, Danesh J, , 2009. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 302: 412423.[Crossref] [Google Scholar]
  55. Nieto FJ, Sorlie P, Comstock GW, Wu K, Adam E, Melnick JL, Szklo M, , 1997. Cytomegalovirus infection, lipoprotein(a), and hypercoagulability: an atherogenic link? Arterioscler Thromb Vasc Biol 17: 17801785.[Crossref] [Google Scholar]
  56. Angchaisuksiri P, , 2014. Coagulopathy in malaria. Thromb Res 133: 59.[Crossref] [Google Scholar]
  57. Sammalkorpi K, Valtonen V, Kerttula Y, Nikkila E, Taskinen MR, , 1988. Changes in serum lipoprotein pattern induced by acute infections. Metabolism 37: 859865.[Crossref] [Google Scholar]
  58. Auerbach BJ, Parks JS, , 1989. Lipoprotein abnormalities associated with lipopolysaccharide-induced lecithin: cholesterol acyltransferase and lipase deficiency. J Biol Chem 264: 1026410270. [Google Scholar]
  59. Ettinger WH, Miller LD, Albers JJ, Smith TK, Parks JS, , 1990. Lipopolysaccharide and tumor necrosis factor cause a fall in plasma concentration of lecithin: cholesterol acyltransferase in cynomolgus monkeys. J Lipid Res 31: 10991107. [Google Scholar]
  60. Memon RA, Grunfeld C, Moser AH, Feingold KR, , 1993. Tumor necrosis factor mediates the effects of endotoxin on cholesterol and triglyceride metabolism in mice. Endocrinology 132: 22462253.[Crossref] [Google Scholar]
  61. Feingold KR, Hardardottir I, Memon R, Krul EJ, Moser AH, Taylor JM, Grunfeld C, , 1993. Effect of endotoxin on cholesterol biosynthesis and distribution in serum lipoproteins in Syrian hamsters. J Lipid Res 34: 21472158. [Google Scholar]
  62. Abarca S, Garcia R, , 1993. Cholesterol metabolism in rat adrenal gland during reversible endotoxic shock. Eur J Biochem 211: 829834.[Crossref] [Google Scholar]
  63. Cetinkaya A, Erden A, Avci D, Karagoz H, Karahan S, Basak M, Bulut K, Gencer V, Mutlu H, , 2014. Is hypertriglyceridemia a prognostic factor in sepsis? Ther Clin Risk Manag 10: 147150. [Google Scholar]
  64. Sammalkorpi K, Valtonen V, Kerttula Y, Nikkila E, Taskinen MR, , 1988. Changes in serum lipoprotein pattern induced by acute infections. Metabolism 37: 859865.[Crossref] [Google Scholar]
  65. Nassaji M, Ghorbani R, , 2012. Plasma lipid levels in patients with acute bacterial infections. Turk J Med Sci 42: 465469. [Google Scholar]
  66. Akerlund B, Carlson LA, Jarstrand C, , 1986. Dyslipoproteinemia in patients with severe bacterial infections. Scand J Infect Dis 18: 539545.[Crossref] [Google Scholar]
  67. Delgado-Rodriguez M, Medina-Cuadros M, Martinez-Gallego G, Sillero-Arenas M, , 1997. Total cholesterol, HDL-cholesterol, and risk of nosocomial infection: a prospective study in surgical patients. Infect Control Hosp Epidemiol 18: 918.[Crossref] [Google Scholar]
  68. Fujioka H, Phelix CF, Friedland RP, Zhu X, Perry EA, Castellani RJ, Perry G, , 2013. Apolipoprotein E4 prevents growth of malaria at the intraerythrocyte stage: implications for differences in racial susceptibility to Alzheimer's disease. J Health Care Poor Underserved 24: 7078.[Crossref] [Google Scholar]
  69. Rougeron V, Woods CM, Tiedje KE, Bodeau-Livinec F, Migot-Nabias F, Deloron P, Luty AJ, Fowkes FJ, Day KP, , 2013. Epistatic interactions between apolipoprotein E and hemoglobin S genes in regulation of malaria parasitemia. PLoS One 8: e76924.[Crossref] [Google Scholar]
  70. Hardardottir I, Grunfeld C, Feingold KR, , 1995. Effects of endotoxin on lipid metabolism. Biochem Soc Trans 23: 10131018.[Crossref] [Google Scholar]
  71. Hanscheid T, Grobusch MP, , 2002. How useful is PCR in the diagnosis of malaria? Trends Parasitol 18: 395398.[Crossref] [Google Scholar]
  72. Smith T, Felger I, Tanner M, Beck HP, , 1999. Premunition in Plasmodium falciparum infection: insights from the epidemiology of multiple infections. Trans R Soc Trop Med Hyg 93 (Suppl 1): 5964.[Crossref] [Google Scholar]
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  • Received : 03 Sep 2016
  • Accepted : 03 Nov 2016

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