• 1.

    World Health Organization , 2020. World Malaria Report 2020. Geneva, Switzerland: WHO.

  • 2.

    White NJ, 2018. Anaemia and malaria. Malar J 17: 371.

  • 3.

    Pathak VA, Ghosh K, 2016. Erythropoiesis in Malaria Infections and Factors Modifying the Erythropoietic Response. Available at: https://www.hindawi.com/journals/anemia/2016/9310905/. Accessed February 29, 2016.

  • 4.

    Teh RN, Sumbele IUN, Meduke DN, Ojong ST, Kimbi HK, 2018. Malaria parasitaemia, anaemia and malnutrition in children less than 15 years residing in different altitudes along the slope of Mount Cameroon: prevalence, intensity and risk factors. Malar J 17: 336.

    • Search Google Scholar
    • Export Citation
  • 5.

    Sumbele IUN, Sama SO, Kimbi HK, Taiwe GS, 2016. Malaria, moderate to severe anaemia, and malarial anaemia in children at presentation to hospital in the Mount Cameroon area: a cross-sectional study. Anemia 2016: 12.

    • Search Google Scholar
    • Export Citation
  • 6.

    Achidi EA, Apinjoh TO, Anchang-Kimbi JK, Mugri RN, Ngwai AN, Yafi CN, 2012. Severe and uncomplicated falciparum malaria in children from three regions and three ethnic groups in Cameroon: prospective study. Malar J 11: 215.

    • Search Google Scholar
    • Export Citation
  • 7.

    Kateera F, Ingabire CM, Hakizimana E, Kalinda P, Mens PF, Grobusch MP, Mutesa L, van Vugt M, 2015. Malaria, anaemia and under-nutrition: three frequently co-existing conditions among preschool children in rural Rwanda. Malar J 14: 440.

    • Search Google Scholar
    • Export Citation
  • 8.

    Nebl T, De Veer MJ, Schofield L, 2005. Stimulation of innate immune responses by malarial glycosylphosphatidylinositol via pattern recognition receptors. Parasitology 130 (Suppl ):S45S62.

    • Search Google Scholar
    • Export Citation
  • 9.

    Coban C et al., 2005. Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J Exp Med 201: 1925.

  • 10.

    Pichyangkul S et al., 1950. 2004. Malaria blood stage parasites activate human plasmacytoid dendritic cells and murine dendritic cells through a Toll-like receptor 9-dependent pathway. J Immunol Baltim Md 172: 49264933.

    • Search Google Scholar
    • Export Citation
  • 11.

    Pham T-T, Lamb TJ, Deroost K, Opdenakker G, den Steen PEV, 2021. Hemozoin in malarial complications: more questions than answers. Trends Parasitol 37: 226239.

    • Search Google Scholar
    • Export Citation
  • 12.

    Netea MG, Kullberg BJ, Van der Meer JWM, 2000. Circulating cytokines as mediators of fever. Clin Infect Dis 31: S178S184.

  • 13.

    Ross R, Thomson D, 1910. Some enumerative studies on malarial fever. Proc R Soc 83: 159173.

  • 14.

    Gatton ML, Cheng Q, 2002. Evaluation of the pyrogenic threshold for Plasmodium falciparum malaria in naive individuals. Am J Trop Med Hyg 66: 467473.

    • Search Google Scholar
    • Export Citation
  • 15.

    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.

    • Search Google Scholar
    • Export Citation
  • 16.

    Dollat M, Talla C, Sokhna C, Diene Sarr F, Trape J-F, Richard V, 2019. Measuring malaria morbidity in an area of seasonal transmission: Pyrogenic parasitemia thresholds based on a 20-year follow-up study. PLOS ONE 14: e0217903.

    • Search Google Scholar
    • Export Citation
  • 17.

    Rogier C, Commenges D, Trape JF, 1996. Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations. Am J Trop Med Hyg 54: 613619.

    • Search Google Scholar
    • Export Citation
  • 18.

    Roucher C, Rogier C, Dieye-Ba F, Sokhna C, Tall A, Trape J-F, 2012. Changing malaria epidemiology and diagnostic criteria for Plasmodium falciparum clinical malaria. PLOS ONE 7: 9.

    • Search Google Scholar
    • Export Citation
  • 19.

    Ashley EA, White NJ, 2014. The duration of Plasmodium falciparum infections. Malar J 13: 500.

  • 20.

    Nzobo BJ, Ngasala BE, Kihamia CM, 2015. Prevalence of asymptomatic malaria infection and use of different malaria control measures among primary school children in Morogoro Municipality, Tanzania. Malar J 14: 491.

    • Search Google Scholar
    • Export Citation
  • 21.

    de Mast Q, Syafruddin D, Keijmel S, Riekerink TO, Deky O, Asih PB, Swinkels DW, van der Ven AJ, 2010. Increased serum hepcidin and alterations in blood iron parameters associated with asymptomatic P. falciparum and P. vivax malaria. Haematologica 95: 10681074.

    • Search Google Scholar
    • Export Citation
  • 22.

    de Mast Q, Brouwers J, Syafruddin D, Bousema T, Baidjoe AY, de Groot PG, van der Ven AJ, Fijnheer R, 2015. Is asymptomatic malaria really asymptomatic? Hematological, vascular and inflammatory effects of asymptomatic malaria parasitemia. J Infect 71: 587596.

    • Search Google Scholar
    • Export Citation
  • 23.

    Jeremiah ZA, Uko EK, Buseri FI, Jeremiah TA, 2007. Malarial iron-deficiency anaemia among asymptomatic Nigerian children. J Nutr Environ Med 16: 231–241.

    • Search Google Scholar
    • Export Citation
  • 24.

    Kurtzhals JA, Addae MM, Akanmori BD, Dunyo S, Koram KA, Appawu MA, Nkrumah FK, Hviid L, 1999. Anaemia caused by asymptomatic Plasmodium falciparum infection in semi-immune African schoolchildren. Trans R Soc Trop Med Hyg 93: 623627.

    • Search Google Scholar
    • Export Citation
  • 25.

    World Health Organization , 2008. Worldwide Prevalence of Anemia 1993–2005. Geneva, Switzerland: WHO.

  • 26.

    Verhoef H, 2010. Asymptomatic malaria in the etiology of iron deficiency anemia: a malariologist’s viewpoint. Am J Clin Nutr 92: 12851286.

    • Search Google Scholar
    • Export Citation
  • 27.

    Essangui E et al., 2019. Demographical, hematological and serological risk factors for Plasmodium falciparum gametocyte carriage in a high stable transmission zone in Cameroon. PLOS ONE 14: e0216133.

    • Search Google Scholar
    • Export Citation
  • 28.

    Antonio-Nkondjio C, Ndo C, Njiokou F, Bigoga JD, Awono-Ambene P, Etang J, Ekobo AS, Wondji CS, 2019. Review of malaria situation in Cameroon: technical viewpoint on challenges and prospects for disease elimination. Parasit Vectors 12: 501.

    • Search Google Scholar
    • Export Citation
  • 29.

    Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565568.

    • Search Google Scholar
    • Export Citation
  • 30.

    Snounou G, Pinheiro L, Gonçalves A, Fonseca L, Dias F, Brown KN, do Rosario VE, 1993. The importance of sensitive detection of malaria parasites in the human and insect hosts in epidemiological studies, as shown by the analysis of field samples from Guinea Bissau. Trans R Soc Trop Med Hyg 87: 649653.

    • Search Google Scholar
    • Export Citation
  • 31.

    Ranford-Cartwright LC, Taylor J, Umasunthar T, Taylor LH, Babiker HA, Lell B, Schmidt-Ott JR, Lehman LG, Walliker D, Kremsner PG, 1997. Molecular analysis of recrudescent parasites in a Plasmodium falciparum drug efficacy trial in Gabon. Trans R Soc Trop Med Hyg 91: 719724.

    • Search Google Scholar
    • Export Citation
  • 32.

    Pinkevych M, Petravic J, Chelimo K, Vulule J, Kazura JW, Moormann AM, Davenport MP, 2014. Decreased growth rate of P. falciparum blood stage parasitemia with age in a holoendemic population. J Infect Dis 209: 11361143.

    • Search Google Scholar
    • Export Citation
  • 33.

    Slater HC et al., 2019. The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density. Nat Commun 10: 1433.

    • Search Google Scholar
    • Export Citation
  • 34.

    Organisation mondiale de la Santé, 2011. Concentrations en hémoglobine permettant de diagnostiquer l’anémie et d’en évaluer la sévérité. Genève: OMS.

    • Search Google Scholar
    • Export Citation
  • 35.

    Guerra M, de Sousa B, Ndong-Mabale N, Berzosa P, Arez AP, 2018. Malaria determining risk factors at the household level in two rural villages of mainland Equatorial Guinea. Malar J 17: 203.

    • Search Google Scholar
    • Export Citation
  • 36.

    Doolan DL, Dobano C, Baird JK, 2009. Acquired immunity to malaria. Clin Microbiol Rev 22: 1336.

  • 37.

    Tientche B, Smith Asaah DNA, Fru-Cho J, Nkuo-Akenji TK, 2016. Asymptomatic malaria parasitaemia in school children of Ekondo Titi sub-division, Cameroon. Int J Environ Res Public Health 3: 182190.

    • Search Google Scholar
    • Export Citation
  • 38.

    Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L, 2013. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther 11: 623639.

    • Search Google Scholar
    • Export Citation
  • 39.

    Pinkevych M, Petravic J, Chelimo K, Kazura JW, Moormann AM, Davenport MP, 2012. The dynamics of naturally acquired immunity to Plasmodium falciparum infection. PLOS Comput Biol 8: e1002729.

    • Search Google Scholar
    • Export Citation
  • 40.

    Murphy WG, 2014. The sex difference in haemoglobin levels in adults—mechanisms, causes, and consequences. Blood Rev 28: 4147.

  • 41.

    Bouyou-Akotet MK, Mawili Mboumba DP, Kendjo E, Mbadinga F, Obiang-Bekale N, Mouidi P, Kombila M, 2013. Anaemia and severe malarial anaemia burden in febrile Gabonese children: a nine-year health facility based survey. J Infect Dev Ctries 7: 983989.

    • Search Google Scholar
    • Export Citation
  • 42.

    Nkuo-Akenji TK, Chi PC, Cho JF, Ndamukong KKJ, Sumbele I, 2006. Malaria and helminth co-infection in children living in a malaria endemic setting of mount Cameroon and predictors of anemia. J Parasitol 92: 11911195.

    • Search Google Scholar
    • Export Citation
  • 43.

    Arese P, Schwarzer E, 1997. Malarial pigment (haemozoin): a very active ‘inert’ substance. Ann Trop Med Parasitol 91: 501516.

  • 44.

    Dufour C, Corcione A, Svahn J, Haupt R, Poggi V, Béka’ssy AN, Scimè R, Pistorio A, Pistoia V, 2003. TNF-α and IFN-γ are overexpressed in the bone marrow of Fanconi anemia patients and TNF-α suppresses erythropoiesis in vitro. Blood 102: 20532059.

    • Search Google Scholar
    • Export Citation
  • 45.

    Keller CC, Kremsner PG, Hittner JB, Misukonis MA, Weinberg JB, Perkins DJ, 2004. Elevated nitric oxide production in children with malarial anemia: hemozoin-induced nitric oxide synthase type 2 transcripts and nitric oxide in blood mononuclear cells. Infect Immun 72: 48684873.

    • Search Google Scholar
    • Export Citation
  • 46.

    Totino PRR, Daniel-Ribeiro CT, Ferreira-da-Cruz M de F, 2016. Evidencing the role of erythrocytic apoptosis in malarial anemia. Front Cell Infect Microbiol 6: 176.

    • Search Google Scholar
    • Export Citation
  • 47.

    Mindukshev IV, Rukoiatkina NI, Dobrylko IA, Skverchinskaia EA, Nikitina ER, Krivoshlyk VV, Gambarian SP, Krivchenko AI, 2013. Characterisation of enucleated cells apoptosis: human platelets and erythrocytes. Ross Fiziol Zh Im I M Sechenova 99: 92110.

    • Search Google Scholar
    • Export Citation
  • 48.

    Daniel-Ribeiro CT, Zanini G, 2000. Autoimmunity and malaria: what are they doing together? Acta Trop 76: 205221.

  • 49.

    Waitumbi JN, Opollo MO, Muga RO, Misore AO, Stoute JA, 2000. Red cell surface changes and erythrophagocytosis in children with severe Plasmodium falciparum anemia. Blood 95: 14811486.

    • Search Google Scholar
    • Export Citation
  • 50.

    Cucunubá ZM, Guerra AP, Rahirant SJ, Rivera JA, Cortés LJ, Nicholls RS, 2008. Asymptomatic Plasmodium spp. infection in Tierralta, Colombia. Mem Inst Oswaldo Cruz 103: 668673.

    • Search Google Scholar
    • Export Citation
 
 

 

 

 

 

 

 

High Prevalence of Asymptomatic Malarial Anemia and Association with Early Conversion from Asymptomatic to Symptomatic Infection in a Plasmodium falciparum Hyperendemic Setting in Cameroon

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  • 1 Molecular Parasitology Laboratory, Centre Pasteur du Cameroun, Yaounde, Cameroon;
  • | 2 Department of Animal Biology and Physiology of the University of Yaoundé I, Yaounde, Cameroon;
  • | 3 Department of Biochemistry, University of Douala, Douala, Cameroon;
  • | 4 Department of Pathology, University of Utah, Salt Lake City, Utah;
  • | 5 Department of Medical Laboratory Sciences, University of Buea, Buea, Cameroon

ABSTRACT.

Asymptomatic malarial parasitemia is highly prevalent in Plasmodium falciparum endemic areas and often associated with increased prevalence of mild to moderate anemia. The aim of this study was to assess the prevalence of anemia during asymptomatic malaria parasitemia and its interplay with persistent infection in highly exposed individuals. A household-based longitudinal survey was undertaken in a malaria hyperendemic area in Cameroon using multiplex nested polymerase chain reaction to detect plasmodial infections. Residents with P. falciparum asymptomatic parasitemia were monitored over a 3-week period with the aid of structured questionnaires and weekly measurements of axillary temperatures. Of the 353 individuals included (median age: 26 years, range 2–86 years, male/female sex ratio 0.9), 328 (92.9%) were positive for malaria parasitemia of whom 266 (81.1%) were asymptomatic carriers. The prevalence of anemia in the study population was 38.6%, of which 69.2% were asymptomatic. Multivariate analyses identified high parasitemia (> 327 parasites/µL) and female gender as associated risk factors of asymptomatic malarial anemia in the population. Furthermore, risk analyses revealed female gender and anemia at the time of enrolment as key predictors of early development of febrile illness (< 3 weeks post enrolment) among the asymptomatic individuals. Together, the data reveal an extremely high prevalence of asymptomatic malaria parasitemia and anemia in the study area, unveiling for the first time the association of asymptomatic malarial anemia with early clinical conversion from asymptomatic to symptomatic infection. Furthermore, these findings underscore the negative impact of asymptomatic malaria parasitemia on individual health, necessitating the development of appropriate control and preventive measures.

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Author Notes

Address correspondence to Lawrence Ayong, Molecular Parasitology Laboratory, Centre Pasteur du Cameroun, BP 1274 Yaounde, Cameroon. E-mail: layong05@yahoo.co.uk

Financial support: This work was financially supported through a capacity building grant from the Institute Pasteur International Division to L. A.

Authors’ addresses: Balotin Fogang and Christiane Donkeu, Molecular Parasitology Laboratory, Centre Pasteur du Cameroun, Yaounde, Cameroon, and Department of Animal Biology and Physiology of the University of Yaoundé I, Yaounde, Cameroon, E-mails: b.fogang@yahoo.fr and donkeu.christiane@yahoo.fr. Marie Florence Biabi, Molecular Parasitology Laboratory, Centre Pasteur du Cameroun, Yaounde, Cameroon, and Department of Biochemistry, University of Douala, Douala, Cameroon, E-mail: bite_marie@yahoo.fr. Rosette Megnekou, Department of Animal Biology and Physiology of the University of Yaoundé I, Yaounde, Cameroon, E-mail: megnekor@yahoo.fr. Franklin M. Maloba, Molecular Parasitology Laboratory, Centre Pasteur du Cameroun, Yaounde, Cameroon, and Department of Pathology, University of Utah, Salt Lake City, UT, E-mail: franklin.maloba@path.utah.edu. Estelle Essangui, Marie Kapen, Rodrigue Keumoe, Sandrine Nsango, Carole Eboumbou, and Lawrence Ayong , Molecular Parasitology Laboratory, Centre Pasteur du Cameroun, Yaounde, Cameroon, E-mails: essanguisam100@yahoo.fr, kapenmffo@gmail.com, rkeumoe@yahoo.fr, nsango2013@yahoo.fr, elsecarole@yahoo.fr, and ayong@pasteur-yaounde.org. Glwadys Cheteug and Sylvie Kemleu, Molecular Parasitology Laboratory, Centre Pasteur du Cameroun, Yaounde, Cameroon, and Department of Medical Laboratory Sciences, University of Buea, Buea, Cameroon, E-mails: glwadys2011@gmail.com and kemleufr@yahoo.fr. Tracey J. Lamb, Department of Pathology, University of Utah, Salt Lake City, UT, E-mail: tracey.lamb@path.utah.edu.

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