PIGMENTED MONOCYTES ARE NEGATIVE CORRELATES OF PROTECTION AGAINST SEVERE AND COMPLICATED MALARIA IN UGANDAN CHILDREN

GODFREY MUJUZI Med Biotech Laboratories, Kampala, Uganda

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BETTY MAGAMBO Med Biotech Laboratories, Kampala, Uganda

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BRENDA OKECH Med Biotech Laboratories, Kampala, Uganda

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THOMAS G. EGWANG Med Biotech Laboratories, Kampala, Uganda

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Pigmented leukocytes are reported to be associated with severe malaria (SM). Blood smears from a case-control study of SM conducted in Apac Hospital in Northern Uganda were examined for pigmented leukocytes to investigate their association with measures of disease and clinical immunity in children less than 5 years old. Pigmented leukocytes, predominated by monocytes, were significantly greater in number in SM by comparison with uncomplicated malaria (UM). SM children with no pigmented leukocytes had significantly elevated hemoglobin, packed cell volumes, and titers of IgG anti-SERA5 by comparison with SM children with pigmented leukocytes. These differences were not observed in UM. A Spearman rank correlation analysis showed, in addition, a negative but weak correlation between pigmented monocytes and titers of IgG anti-Plasmodium falciparum lysate and IgG anti-EBA-175 in both SM and UM children. Thus, numbers of pigmented monocytes might be negative correlates of clinical immunity in a region of holoendemic malaria.

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  • 1

    Orjih AU, Ryerse JS, Fitch CD, 1994. Hemoglobin catabolism and the killing of intraerythrocytic Plasmodium falciparum by chloroquine. Experientia 50 :34–39.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Orjih AU, Fitch CD, 1993. Hemozoin production by Plasmodium falciparum: variation with strain and exposure to chloroquine. Biochim Biophys Acta 1157 :270–274.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Olliaro P, Lombardi L, Frigerio S, Basilico N, Taramelli D, Monti D, 2000. Phagocytosis of hemozoin (native and synthetic malaria pigment), and Plasmodium falciparum intraerythrocytic stage parasites by human and mouse phagocytes. Ultrastruct Pathol 24 :9–13.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Rudzinska MA, Trager W, Bray RS, 1965. Pinocytotic uptake and the digestion of hemoglobin in malaria parasites. J Protozool 12 :563–576.

  • 5

    Slater AF, Swiggard JW, Orton BR, Flitter WD, Goldberg DE, Cerami A, Henderson GB, 1991. An iron-carboxylate bond links the heme units of malaria pigment. Proc Natl Acad Sci U S A 88 :325–329.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Pagola S, Stephens PW, Bohle DS, Kosar AD, Madsen SK, 2000. The structure of malaria pigment betahaematin. Nature 404 :307–310.

  • 7

    Laveran CLA, A newly discovered parasite in the blood of patients suffering from malaria. In: Kean BH, Mott KE, Russell AJ, eds. Tropical Medicine and Parasitology, Classic Investigations. Vol. 1. Ithaca, NY: Cornell University Press; 1978:23–26.

    • PubMed
    • Export Citation
  • 8

    Nguyen PH, Day N, Pram TD, Ferguson DJ, White NJ, 1995. Intraleucocytic malaria pigment and prognosis in severe malaria. Trans R Soc Trop Med Hyg 89 :200–204.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Metzger WG, Mordmuller BG, Kremsner PG, 1995. Malaria pigment in leucocytes. Trans R Soc Trop Med Hyg 89 :637–638.

  • 10

    Amodu OK, Adeyemo AA, Olumese PE, Ketiku O, Gbadegesin RA, 1997. Intraleucocyte malaria pigment in asymptomatic and uncomplicated malaria. East Afr Med J 74 :714–716.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Amodu OK, Adeyemo AA, Olumese PE, Gbadegesin RA, 1998. Intraleucocytic malaria pigment and clinical severity of malaria in children. Trans R Soc Trop Med Hyg 92 :54–56.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Lyke KE, Diallo DA, Dicko A, Kone A, Coulibaly D, Guindo A, Cissoko Y, Sangare L, Coulibaly S, Dakouo B, Taylor TE, Doumbo OK, Plowe CV, 2003. Association of intraleukocytic Plasmodium falciparum malaria pigment with disease severity, clinical manifestations, and prognosis in severe malaria. Am J Trop Med Hyg 69 :253–259.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Deshpande P, Shastry P, 2004. Modulation of cytokine profiles by malaria pigment-hemozoin: role of IL-10 in suppression of proliferative responses of mitogen-stimulated human PBMC. Cytokine 28 :205–213.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Perkins DJ, Moore JM, Otieno J, Shi YP, Nahlen BL, Udhayakumar V, Lal AA, 2003. In vivo acquisition of hemozoin by placental mononuclear cells suppresses PGE2, TNF-alpha, and IL-10. Biochem Biophys Res Commun 311 :839–846.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Skorokhod OA, Alessio M, Mordmuller B, Arese P, Schwarzer E, 2004. Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: a peroxisome proliferator-activated receptor-gamma-mediated effect. J Immunol 173 :4066–4074.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Luty AJ, Perkins DJ, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Weinberg JB, Kremsner PG, 2000. Low interleukin-12 activity in severe Plasmodium falciparum malaria. Infect Immun 68 :3909–3915.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Egwang TG, Apio B, Riley E, Okello D, 2000. Plasmodium falciparum malariometric indices in Apac district, northern Uganda. East Afr Med J 77 :413–416.

  • 18

    Okech BA, Mujuzi G, Ogwal A, Shirai H, Horii T, Egwang TG, 2006. High titers of IgG antibodies against Plasmodium falciparum serine repeat antigen 5 (SERA5) are associated with protection against severe malaria in Ugandan children. Am J Trop Med Hyg 74 :191–197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    World Health Organization, 2000. Severe falciparum malaria. Trans R. Soc Trop Med Hyg 94 (Suppl 1):S1–S90.

  • 20

    Greenwood BM, Armstrong JRM, 1991. Comparison of two simple methods for determining malaria parasite densities. Trans R Soc Trop Med Hyg 85 :186–188.

  • 21

    Ministry of Health, Kampala: Uganda Government. 2004. Annual Report.

  • 22

    Snow RW, Omumbo JA, Lowe B, Molyneaux 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
  • 23

    Reyburn H, Mbatia R, Drakeley C, Bruce J, Carneiro I, Olomi R, Cox J, Nkya WM, Lemnge M, Greenwood BM, Riley EM, 2005. Association of transmission intensity and age with clinical manifestations and case fatality of severe Plasmodium falciparum malaria. JAMA 293 :1461–1470.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Henning L, Schellenberg D, Smith T, Henning D, Alonso P, Tanner M, Mshinda H, Beck HP, Felger I, 2004. A prospective study of Plasmodium falciparum multiplicity of infection and morbidity in Tanzanian children. Trans R Soc Trop Med Hyg. 98 :687–694.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Imbert P, Sartelet I, Rogier C, Ka S, Baujat G, Candito D, 1997. Severe malaria among children in a low seasonal transmission area, Dakar, Senegal: influence of age on clinical presentation. Trans R Soc Trop Med Hyg 91 :22–24.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Pandey KC, Singh S, Pattnaik P, Pillai CR, Pillai U, Lynn A, Jain SK, Chitnis CE, 2002. Bacterially expressed and refolded receptor binding domain of Plasmodium falciparum EBA-175 elicits invasion inhibitory antibodies. Mol Biochem Parasitol 123 :23–33.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Kramer B, Grobusch MP, Suttorp N, Neukammer J, Rinneberg H, 2001. Relative frequency of malaria pigment-carrying monocytes of nonimmune and semi-immune patients from flow cytometric depolarized side scatter. Cytometry 45 :133–140.

    • PubMed
    • Search Google Scholar
    • Export Citation
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