Malaria Parasitemia and CD4 T Cell Count, Viral Load, and Adverse HIV Outcomes Among HIV-Infected Pregnant Women in Tanzania

Molly F. Franke Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts

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Donna Spiegelman Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts

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Amara Ezeamama Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts

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Said Aboud Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts

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Gernard I. Msamanga Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts

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Saurabh Mehta Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts

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Wafaie W. Fawzi Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts

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DOI:
https://doi.org/10.4269/ajtmh.2010.09-0477
Volume/Issue:
Volume 82: Issue 4
Page(s):
556–562
Restricted access
Get Permissions

We examined the cross-sectional relationships between malaria parasitemia and CD4 T cell count and viral load among human immunodeficiency virus (HIV)-infected pregnant women. We then followed women to investigate whether or not baseline parasitemia predicted CD4 T cell counts or viral loads > 90 days post-baseline or predicted time to HIV disease stage 3 or 4 or acquired immune deficiency syndrome (AIDS)-related death (ARD). Parasitemia level was nonlinearly associated with viral load at baseline and among measurements taken > 90 days post-baseline; women with low baseline parasitemia, versus none, had higher viral loads at both time points. Any baseline parasitemia predicted an increased rate of ARD among women with baseline CD4 T cell counts ≥ 500 cells/µL (ratio rate [RR] = 2.6; 95% confidence interval [CI] = 1.1–6.0; P test for heterogeneity = 0.05). Further study is warranted to determine whether or not parasitemia is especially detrimental to individuals with lower levels of immunosuppression or chronic low parasitemia.

Author Notes

*Address correspondence to Molly F. Franke, 641 Huntington Avenue, 4th Floor, Boston, MA 02115. E-mail: mfranke@hsph.harvard.edu

Financial support: The randomized trial of multivitamin supplementation was funded by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R01HD032257-13). M.F.F. received support from the National Institute of Allergy and Infectious Diseases Pre-Doctoral Training Program in the Epidemiology of Infectious Diseases and Biodefense (T32 AI007535).

Authors' addresses: Molly F. Franke, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, E-mail: mfranke@hsph.harvard.edu. Donna Spiegelman, Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, MA 02115, E-mail: stdls@channing.harvard.edu. Amara Ezeamama, Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, E-mail: aezeamam@hsph.harvard.edu. Said Aboud Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, E-mail: aboudsaid@yahoo.com. Gernard I. Msamanga, Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, E-mail: gmsamanga@muhas.ac.tz. Saurabh Mehta, Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, E-mail: smehta@hsph.harvard.edu. Wafaie W. Fawzi, Departments of Epidemiology, Nutrition, and Global Health and Population, Harvard School of Public Health, Boston, MA 02115, E-mail: mina@hsph.harvard.edu.

Copyright:
©The American Society of Tropical Medicine and Hygiene 2010
Received:
19 Aug 2009
|
Accepted:
07 Jan 2010
|
Published Online:
05 Apr 2010
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
  • 1.

    World Health Organization, UNAIDS, 2008. Towards Universal Access: Scaling Up Priority HIV/AIDS Interventions in the Health Sector, Progress Report. Available at: http://www.unaidsrstesa.org/userfiles/file/towards_universal_access_report_2008%5B1%5D(1).pdf. Accessed March 7, 2009.

    • Search Google Scholar
    • Export Citation
  • 2.

    World Health Organization, 2008. Antiretroviral Therapy for HIV Infection in Adults and Adolescents: Recommendations for a Public Health Approach, 2006 Revision. Available at: http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf. Accessed March 7, 2009.

    • Search Google Scholar
    • Export Citation
  • 3.

    Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg KA, 2003. Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa. Clin Infect Dis 36: 652–662.

    • Search Google Scholar
    • Export Citation
  • 4.

    French N, Nakiyingi J, Lugada E, Watera C, Whitworth JA, Gilks CF, 2001. Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS 15:899–906.

    • Search Google Scholar
    • Export Citation
  • 5.

    Ladner J, Leroy V, Simonon A, Karita E, Bogaerts J, De Clercq A, Van De Perre P, Dabis F, 2002. HIV infection, malaria, and pregnancy: a prospective cohort study in Kigali, Rwanda. Am J Trop Med Hyg 66: 56–60.

    • Search Google Scholar
    • Export Citation
  • 6.

    Laufer MK, van Oosterhout JJ, Thesing PC, Thumba F, Zijlstra EE, Graham SM, Taylor TE, Plowe CV, 2006. Impact of HIV-associated immunosuppression on malaria infection and disease in Malawi. J Infect Dis 193: 872–878.

    • Search Google Scholar
    • Export Citation
  • 7.

    Patnaik P, Jere CS, Miller WC, Hoffman IF, Wirima J, Pendame R, Meshnick SR, Taylor TE, Molyneux ME, Kublin JG, 2005. Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi. J Infect Dis 192: 984–991.

    • Search Google Scholar
    • Export Citation
  • 8.

    Kamya MR, Gasasira AF, Yeka A, Bakyaita N, Nsobya SL, Francis D, Rosenthal PJ, Dorsey G, Havlir D, 2006. Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study. J Infect Dis 193: 9–15.

    • Search Google Scholar
    • Export Citation
  • 9.

    Whitworth J, Morgan D, Quigley M, Smith A, Mayanja B, Eotu H, Omoding N, Okongo M, Malamba S, Ojwiya A, 2000. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 356: 1051–1056.

    • Search Google Scholar
    • Export Citation
  • 10.

    Froebel K, Howard W, Schafer JR, Howie F, Whitworth J, Kaleebu P, Brown AL, Riley E, 2004. Activation by malaria antigens renders mononuclear cells susceptible to HIV infection and re-activates replication of endogenous HIV in cells from HIV-infected adults. Parasite Immunol 26: 213–217.

    • Search Google Scholar
    • Export Citation
  • 11.

    Pisell TL, Hoffman IF, Jere CS, Ballard SB, Molyneux ME, Butera ST, Lawn SD, 2002. Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection. AIDS 16: 1503–1509.

    • Search Google Scholar
    • Export Citation
  • 12.

    Xiao L, Owen SM, Rudolph DL, Lal RB, Lal AA, 1998. Plasmodium falciparum antigen-induced human immunodeficiency virus type 1 replication is mediated through induction of tumor necrosis factor-alpha. J Infect Dis 177: 437–445.

    • Search Google Scholar
    • Export Citation
  • 13.

    O'Brien WA, Hartigan PM, Martin D, Esinhart J, Hill A, Benoit S, Rubin M, Simberkoff MS, Hamilton JD, 1996. Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS. N Engl J Med 334: 426–431.

    • Search Google Scholar
    • Export Citation
  • 14.

    Sterling TR, Vlahov D, Astemborski J, Hoover DR, Margolick JB, Quinn TC, 2001. Initial plasma HIV-1 RNA levels and progression to AIDS in women and men. N Engl J Med 344: 720–725.

    • Search Google Scholar
    • Export Citation
  • 15.

    Kapiga SH, Bang H, Spiegelman D, Msamanga GI, Coley J, Hunter DJ, Fawzi WW, 2002. Correlates of plasma HIV-1 RNA viral load among HIV-1-seropositive women in Dar es Salaam, Tanzania. J Acquir Immune Defic Syndr 30: 316–323.

    • Search Google Scholar
    • Export Citation
  • 16.

    Hoffman IF, Jere CS, Taylor TE, Munthali P, Dyer JR, Wirima JJ, Rogerson SJ, Kumwenda N, Eron JJ, Fiscus SA, Chakraborty H, Taha TE, Cohen MS, Molyneux ME, 1999. The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration.AIDS 13: 487–494.

    • Search Google Scholar
    • Export Citation
  • 17.

    Kublin JG, Patnaik P, Jere CS, Miller WC, Hoffman IF, Chimbiya N, Pendame R, Taylor TE, Molyneux ME, 2005. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. Lancet 365: 233–240.

    • Search Google Scholar
    • Export Citation
  • 18.

    Quigley MA, Hewitt K, Mayanja B, Morgan D, Eotu H, Ojwiya A, Whitworth JA, 2005. The effect of malaria on mortality in a cohort of HIV-infected Ugandan adults. Trop Med Int Health 10: 894–900.

    • Search Google Scholar
    • Export Citation
  • 19.

    Fawzi WW, Msamanga GI, Spiegelman D, Urassa EJ, Hunter DJ, 1999. Rationale and design of the Tanzania vitamin and HIV infection trial. Control Clin Trials 20: 75–90.

    • Search Google Scholar
    • Export Citation
  • 20.

    Fawzi WW, Msamanga GI, Spiegelman D, Wei R, Kapiga S, Villamor E, Mwakagile D, Mugusi F, Hertzmark E, Essex M, Hunter DJ, 2004. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 351: 23–32.

    • Search Google Scholar
    • Export Citation
  • 21.

    Tanzania Ministry of Health, 2009. National Medium Term Strategic Plan 2002–2007. Available at: http://www.rollbackmalaria.org/countryaction/nsp/tanzania.pdf. Accessed March 7, 2009.

    • Search Google Scholar
    • Export Citation
  • 22.

    National Bureau of Statistics (Tanzania) and Macro International Inc., 2000. Tanzania Reproductive and Child Health Survey 1999. Calverton, MD: National Bureau of Statistics and Macro International Inc.

    • Search Google Scholar
    • Export Citation
  • 23.

    Trape JF, 1985. Rapid evaluation of malaria parasite density and standardization of thick smear examination for epidemiological investigations. Trans R Soc Trop Med Hyg 79: 181–184.

    • Search Google Scholar
    • Export Citation
  • 24.

    Mulligan JA, Mandike R, Palmer N, Williams H, Abdulla S, Bloland P, Mills A, 2006. The costs of changing national policy: lessons from malaria treatment policy guidelines in Tanzania. Trop Med Int Health 11: 452–461.

    • Search Google Scholar
    • Export Citation
  • 25.

    1990. Interim proposal for a WHO staging system for HIV infection and disease. Wkly Epidemiol Rec 65: 221–224.

  • 26.

    Govindarajulu US, Spiegelman D, Thurston SW, Ganguli B, Eisen EA, 2007. Comparing smoothing techniques in Cox models for exposure-response relationships. Stat Med 26: 3735–3752.

    • Search Google Scholar
    • Export Citation
  • 27.

    Cox DR, 1972. Regression models and life-tables. J R Stat Soc B 34: 187–220.

  • 28.

    Cochran WG, 1950. The comparison of percentages in matched samples. Biometrika 37: 256–266.

  • 29.

    Toossi Z, Mayanja-Kizza H, Hirsch CS, Edmonds KL, Spahlinger T, Hom DL, Aung H, Mugyenyi P, Ellner JJ, Whalen CW, 2001. Impact of tuberculosis (TB) on HIV-1 activity in dually infected patients. Clin Exp Immunol 123: 233–238.

    • Search Google Scholar
    • Export Citation
  • 30.

    Whalen CC, Nsubuga P, Okwera A, Johnson JL, Hom DL, Michael NL, Mugerwa RD, Ellner JJ, 2000. Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda. AIDS 14: 1219–1228.

    • Search Google Scholar
    • Export Citation
  • 31.

    Bodker R, Msangeni HA, Kisinza W, Lindsay SW, 2006. Relationship between the intensity of exposure to malaria parasites and infection in the Usambara Mountains, Tanzania. Am J Trop Med Hyg 74: 716–723.

    • Search Google Scholar
    • Export Citation
  • 32.

    Ladeia-Andrade S, Ferreira MU, de Carvalho ME, Curado I, Coura JR, 2009. Age-dependent acquisition of protective immunity to malaria in riverine populations of the Amazon Basin of Brazil. Am J Trop Med Hyg 80: 452–459.

    • Search Google Scholar
    • Export Citation
  • 33.

    Trape JF, Rogier C, Konate L, Diagne N, Bouganali H, Canque B, Legros F, Badji A, Ndiaye G, Ndiaye P, Brahimi K, Faye O, Druilhe P, Pereira Da Silva L, 1994. The Dielmo project: a longitudinal study of natural malaria infection and the mechanisms of protective immunity in a community living in a holoendemic area of Senegal. Am J Trop Med Hyg 51: 123–137.

    • Search Google Scholar
    • Export Citation
  • 34.

    Mayor A, Aponte JJ, Fogg C, Saute F, Greenwood B, Dgedge M, Menendez C, Alonso PL, 2007. The epidemiology of malaria in adults in a rural area of southern Mozambique. Malar J 6: 3.

    • Search Google Scholar
    • Export Citation
  • 35.

    Van Geertruyden JP, Mulenga M, Kasongo W, Polman K, Colebunders R, Kestens L, D'Alessandro U, 2006. CD4 T-cell count and HIV-1 infection in adults with uncomplicated malaria. J Acquir Immune Defic Syndr 43: 363–367.

    • Search Google Scholar
    • Export Citation
  • 36.

    World Health Organization, 2009. Malaria and HIV Interactions and Their Implications for Public Health Policy. Available at: http://www.who.int/malaria/malaria_HIV/MalariaHIVinteractions_report.pdf. Accessed March 21, 2009.

    • Search Google Scholar
    • Export Citation
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