Development of Clinical Immunity to Malaria in Highland Areas of Low and Unstable Transmission

Melissa A. Rolfes Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Moi University School of Medicine, Eldoret, Kenya; College of Public Health, University of Arizona, Tucson, Arizona; Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Centers for Disease Control and Prevention, Atlanta, Georgia

Search for other papers by Melissa A. Rolfes in
Current site
Google Scholar
PubMed
Close
,
Matthew McCarra Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Moi University School of Medicine, Eldoret, Kenya; College of Public Health, University of Arizona, Tucson, Arizona; Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Centers for Disease Control and Prevention, Atlanta, Georgia

Search for other papers by Matthew McCarra in
Current site
Google Scholar
PubMed
Close
,
Ng'wena G. Magak Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Moi University School of Medicine, Eldoret, Kenya; College of Public Health, University of Arizona, Tucson, Arizona; Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Centers for Disease Control and Prevention, Atlanta, Georgia

Search for other papers by Ng'wena G. Magak in
Current site
Google Scholar
PubMed
Close
,
Kacey C. Ernst Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Moi University School of Medicine, Eldoret, Kenya; College of Public Health, University of Arizona, Tucson, Arizona; Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Centers for Disease Control and Prevention, Atlanta, Georgia

Search for other papers by Kacey C. Ernst in
Current site
Google Scholar
PubMed
Close
,
Arlene E. Dent Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Moi University School of Medicine, Eldoret, Kenya; College of Public Health, University of Arizona, Tucson, Arizona; Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Centers for Disease Control and Prevention, Atlanta, Georgia

Search for other papers by Arlene E. Dent in
Current site
Google Scholar
PubMed
Close
,
Kim A. Lindblade Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Moi University School of Medicine, Eldoret, Kenya; College of Public Health, University of Arizona, Tucson, Arizona; Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Centers for Disease Control and Prevention, Atlanta, Georgia

Search for other papers by Kim A. Lindblade in
Current site
Google Scholar
PubMed
Close
, and
Chandy C. John Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Moi University School of Medicine, Eldoret, Kenya; College of Public Health, University of Arizona, Tucson, Arizona; Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; Centers for Disease Control and Prevention, Atlanta, Georgia

Search for other papers by Chandy C. John in
Current site
Google Scholar
PubMed
Close
Restricted access

In highland areas of unstable, low malaria transmission, the extent to which immunity to uncomplicated malaria develops with age and intermittent parasite exposure has not been well characterized. We conducted active surveillance for clinical malaria during April 2003–March 2005 in two highland areas of western Kenya (Kapsisiywa and Kipsamoite). In both sites, annual malaria incidence was significantly lower in persons ≥ 15 years of age than in persons < 5 years of age (Kapsisiywa: incidence = 382.9 cases/1,000 persons among persons < 1–4 years of age versus 135.1 cases/1,000 persons among persons ≥ 15 years of age; Kipsamoite: incidence = 233.0 cases/1,000 persons in persons < 1–4 years of age versus 43.3 cases/1,000 persons in persons ≥ 15 years of age). In Kapsisiywa, among persons with malaria, parasite density and axillary body temperature were also significantly lower in persons ≥ 15 years of age than in persons < 5 years of age. Even in highland areas of unstable and low malaria transmission, age is associated with development of clinical immunity to malaria.

Author Notes

* Address correspondence to Melissa A. Rolfes, Department of Pediatrics, University of Minnesota, 3-410 MTRF, 2001 6th Street SE, Minneapolis, MN 55455. E-mail: riede056@umn.edu

Financial support: This study was supported in part by National Institutes of Allergy and Infectious Diseases grants U01 AI056270, K08 AI01572, and D43 TW0080085 to Chandy C. John.

Authors' addresses: Melissa A. Rolfes and Matthew McCarra, Department of Pediatrics, University of Minnesota, Minneapolis, MN, E-mails: riede056@umn.edu and mcca0495@umn.edu. Ng'wena G. Magak, Department of Medical Physiology, School of Medicine, Moi University, Eldoret, Kenya, E-mail: gngwena@hotmail.com. Kacey C. Ernst, College of Public Health, University of Arizona, Tucson, AZ, E-mail: kernst@email.arizona.edu. Arlene E. Dent, Center for Global Health and Diseases, Case Western Reserve School of Medicine, Biomedical Research Building, West Administrative Offices #430, Cleveland, OH, E-mail: arlene.dent@case.edu. Kim A. Lindblade, Malaria Branch, Centers for Disease Control and Prevention, Atlanta, GA, E-mail: kil2@cdc.gov. Chandy C. John, Center for Global Pediatrics, Department of Pediatrics, University of Minnesota, Minneapolis, MN, E-mail: ccj@umn.edu.

  • 1.

    World Health Organization, 2011. Roll Back Malaria. Malaria Key Facts. Available at: http://www.rollbackmalaria.org/malariaMessages.html. Accessed July 29, 2011.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Baird JK, 1998. Age-dependent characteristics of protection versus susceptibility to Plasmodium falciparum. Ann Trop Med Parasitol 92: 367390.

  • 3.

    Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60: 641648.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Smith T, Maire N, Dietz K, Killeen GF, Vounatsou P, Molineaux L, Tanner M, 2006. Relationship between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria. Am J Trop Med Hyg 75: 1118.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Carneiro I, Roca-Feltrer A, Griffin JT, Smith L, Tanner M, Schellenberg JA, Greenwood B, Schellenberg D, 2010. Age-patterns of malaria vary with severity, transmission intensity and seasonality in sub-Saharan Africa: a systematic review and pooled analysis. PLoS ONE 5: e8988.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Okiro EA, Al-Taiar A, Reyburn H, Idro R, Berkley JA, Snow RW, 2009. Age patterns of severe paediatric malaria and their relationship to Plasmodium falciparum transmission intensity. Malar J 8: 4.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    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: 14611470.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Bodker R, Akida J, Shayo D, Kisinza W, Msangeni HA, Pedersen EM, Lindsay SW, 2003. Relationship between altitude and intensity of malaria transmission in the Usambara Mountains, Tanzania. J Med Entomol 40: 706717.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Garnham PC, 1945. Malaria epidemics at exceptionally high altitudes. BMJ 2: 4547.

  • 10.

    Guerra CA, Gikandi PW, Tatem AJ, Noor AM, Smith DL, Hay SI, Snow RW, 2008. The limits and intensity of Plasmodium falciparum transmission: implications for malaria control and elimination worldwide. PLoS Med 5: e38.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    John CC, McHugh MM, Moormann AM, Sumba PO, Ofulla AV, 2005. Low prevalence of Plasmodium falciparum infection among asymptomatic individuals in a highland area of Kenya. Trans R Soc Trop Med Hyg 99: 780786.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Hay SI, Noor AM, Simba M, Busolo M, Guyatt HL, Ochola SA, Snow RW, 2002. Clinical epidemiology of malaria in the highlands of western Kenya. Emerg Infect Dis 8: 543548.

  • 13.

    Lindsay SW, Martens WJ, 1998. Malaria in the African highlands: past, present and future. Bull World Health Organ 76: 3345.

  • 14.

    de Zuleuta J, Kafuko GW, McCrae AW, Pedersen CK, Wasswa DF, 1964. A malaria eradication experiment in the highlands of Kigezi (Uganda). East Afr Med J 41: 102120.

  • 15.

    Cohen JM, Ernst KC, Lindblade KA, Vulule JM, John CC, Wilson ML, 2008. Topography-derived wetness indices are associated with household-level malaria risk in two communities in the western Kenyan highlands. Malar J 7: 40.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Noland GS, Hendel-Paterson B, Min XM, Moormann AM, Vulule JM, Narum DL, Lanar DE, Kazura JW, John CC, 2008. Low prevalence of antibodies to preerythrocytic but not blood-stage Plasmodium falciparum antigens in an area of unstable malaria transmission compared to prevalence in an area of stable malaria transmission. Infect Immun 76: 57215728.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    World Health Organization, 1975. Manual of Practical Entomology in Malaria. Part II: Methods and Techniques. Geneva: World Health Organization.

  • 18.

    Shaukat AM, Breman JG, McKenzie FE, 2010. Using the entomological inoculation rate to assess the impact of vector control on malaria parasite transmission and elimination. Malar J 9: 122.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Lines JD, Curtis CF, Wilkes TJ, Njunwa KJ, 1991. Monitoring human-biting mosquitoes (Diptera: Culicidae) in Tanzania with light-traps hung beside mosquito nets. Bull Entomol Res 81: 7784.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Drakeley C, Schellenberg D, Kihonda J, Sousa CA, Arez AP, Lopes D, Lines J, Mshinda H, Lengeler C, Armstrong Schellenberg J, Tanner M, Alonso P, 2003. An estimation of the entomological inoculation rate for Ifakara: a semi-urban area in a region of intense malaria transmission in Tanzania. Trop Med Int Health 8: 767774.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Smith T, Schellenberg JA, Hayes R, 1994. Attributable fraction estimates and case definitions for malaria in endemic areas. Stat Med 13: 23452358.

  • 22.

    Menge DM, Ernst KC, Vulule JM, Zimmerman PA, Guo H, John CC, 2008. Microscopy underestimates the frequency of Plasmodium falciparum infection in symptomatic individuals in a low transmission highland area. Am J Trop Med Hyg 79: 173177.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Gerritsen AA, Kruger P, van der Loeff MF, Grobusch MP, 2008. Malaria incidence in Limpopo Province, South Africa, 1998–2007. Malar J 7: 162.

  • 24.

    Giha HA, Rosthoj S, Dodoo D, Hviid L, Satti GM, Scheike T, Arnot DE, Theander TG, 2000. The epidemiology of febrile malaria episodes in an area of unstable and seasonal transmission. Trans R Soc Trop Med Hyg 94: 645651.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Dicko A, Sagara I, Diemert D, Sogoba M, Niambele MB, Dao A, Dolo G, Yalcouye D, Diallo DA, Saul A, Miller LH, Toure YT, Klion AD, Doumbo OK, 2007. Year-to-year variation in the age-specific incidence of clinical malaria in two potential vaccine testing sites in Mali with different levels of malaria transmission intensity. Am J Trop Med Hyg 77: 10281033.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Kleinschmidt I, Sharp B, 2001. Patterns in age-specific malaria incidence in a population exposed to low levels of malaria transmission intensity. Trop Med Int Health 6: 986991.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Lindblade KA, Katungu I, Wilson ML, 2001. Fever and malaria in highland Uganda. Trans R Soc Trop Med Hyg 95: 502503.

  • 28.

    Trape JF, Lefebvre-Zante E, Legros F, Druilhe P, Rogier C, Bouganali H, Salem G, 1993. Malaria morbidity among children exposed to low seasonal transmission in Dakar, Senegal and its implications for malaria control in tropical Africa. Am J Trop Med Hyg 48: 748756.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    John CC, Riedesel MA, Magak NG, Lindblade KA, Menge DM, Hodges JS, Vulule JM, Akhwale W, 2009. Possible interruption of malaria transmission, highland Kenya, 2007–2008. Emerg Infect Dis 15: 19171924.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Ernst KC, Lindblade KA, Koech D, Sumba PO, Kuwuor DO, John CC, Wilson ML, 2009. Environmental, socio-demographic and behavioural determinants of malaria risk in the western Kenyan highlands: a case-control study. Trop Med Int Health 14: 12581265.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    John CC, Moormann AM, Sumba PO, Ofulla AV, Pregibon DC, Kazura JW, 2004. Gamma interferon responses to Plasmodium falciparum liver-stage antigen 1 and thrombospondin-related adhesive protein and their relationship to age, transmission intensity, and protection against malaria. Infect Immun 72: 51355142.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Drakeley CJ, Carneiro I, Reyburn H, Malima R, Lusingu JP, Cox J, Theander TG, Nkya WM, Lemnge MM, Riley EM, 2005. Altitude-dependent and -independent variations in Plasmodium falciparum prevalence in northeastern Tanzania. J Infect Dis 191: 15891598.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Gupta S, Snow RW, Donnelly CA, Marsh K, Newbold C, 1999. Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med 5: 340343.

  • 34.

    Sagara I, Sangare D, Dolo G, Guindo A, Sissoko M, Sogoba M, Niambele MB, Yalcoue D, Kaslow DC, Dicko A, Klion AD, Diallo D, Miller LH, Toure Y, Doumbo O, 2002. A high malaria reinfection rate in children and young adults living under a low entomological inoculation rate in a periurban area of Bamako, Mali. Am J Trop Med Hyg 66: 310313.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Menegon M, Severini C, Sannella A, Paglia MG, Sangare D, Abdel-Wahab A, Abdel-Muhsin AA, Babiker H, Walliker D, Alano P, 2000. Genotyping of Plasmodium falciparum gametocytes by reverse transcriptase polymerase chain reaction. Mol Biochem Parasitol 111: 153161.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Mwangi TW, Ross A, Snow RW, Marsh K, 2005. Case definitions of clinical malaria under different transmission conditions in Kilifi District, Kenya. J Infect Dis 191: 19321939.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Chandler CI, Drakeley CJ, Reyburn H, Carneiro I, 2006. The effect of altitude on parasite density case definitions for malaria in northeastern Tanzania. Trop Med Int Health 11: 11781184.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Mmbando BP, Lusingu JP, Vestergaard LS, Lemnge MM, Theander TG, Scheike TH, 2009. Parasite threshold associated with clinical malaria in areas of different transmission intensities in north eastern Tanzania. BMC Med Res Methodol 9: 75.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Farcas GA, Zhong KJ, Lovegrove FE, Graham CM, Kain KC, 2003. Evaluation of the Binax NOW ICT test versus polymerase chain reaction and microscopy for the detection of malaria in returned travelers. Am J Trop Med Hyg 69: 589592.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Mason DP, Kawamoto F, Lin K, Laoboonchai A, Wongsrichanalai C, 2002. A comparison of two rapid field immunochromatographic tests to expert microscopy in the diagnosis of malaria. Acta Trop 82: 5159.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Ratsimbasoa A, Randriamanantena A, Raherinjafy R, Rasoarilalao N, Menard D, 2007. Which malaria rapid test for Madagascar? Field and laboratory evaluation of three tests and expert microscopy of samples from suspected malaria patients in Madagascar. Am J Trop Med Hyg 76: 481485.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Baird JK, 1995. Host age as a determinant of naturally acquired immunity to Plasmodium falciparum. Parasitol Today 11: 105111.

Past two years Past Year Past 30 Days
Abstract Views 480 408 25
Full Text Views 421 7 0
PDF Downloads 95 7 0
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save