title: Parasite burden and severity of malaria in Tanzanian children.
abstract: BACKGROUND
  Severe Plasmodium falciparum malaria is a major cause of death in children. The contribution of the parasite burden to the pathogenesis of severe malaria has been controversial.
  
  
  METHODS
  We documented P. falciparum infection and disease in Tanzanian children followed from birth for an average of 2 years and for as long as 4 years.
  
  
  RESULTS
  Of the 882 children in our study, 102 had severe malaria, but only 3 had more than two episodes. More than half of first episodes of severe malaria occurred after a second infection. Although parasite levels were higher on average when children had severe rather than mild disease, most children (67 of 102) had high-density infection (>2500 parasites per 200 white cells) with only mild symptoms before severe malaria, after severe malaria, or both. The incidence of severe malaria decreased considerably after infancy, whereas the incidence of high-density infection was similar among all age groups. Infections before and after episodes of severe malaria were associated with similar parasite densities. Nonuse of bed nets, placental malaria at the time of a woman's second or subsequent delivery, high-transmission season, and absence of the sickle cell trait increased severe-malaria risk and parasite density during infections.
  
  
  CONCLUSIONS
  Resistance to severe malaria was not acquired after one or two mild infections. Although the parasite burden was higher on average during episodes of severe malaria, a high parasite burden was often insufficient to cause severe malaria even in children who later were susceptible. The diverging rates of severe disease and high-density infection after infancy, as well as the similar parasite burdens before and after severe malaria, indicate that naturally acquired resistance to severe malaria is not explained by improved control of parasite density. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
authors.affiliation: From the Laboratory of Malaria Immunology and Vaccinology (B.P.G., M.F., P.E.D.), Laboratory of Clinical Infectious Diseases-Epidemiology Unit (B.P.G., D.R.P.), and Biostatistics Research Branch (C.-Y.H.), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, MD; the Seattle Biomedical Research Institute (R.M., M.F., P.E.D.) and the Fred Hutchinson Cancer Research Center (S.H.) - both in Seattle; and the Mother-Offspring Malaria Studies Project, Muheza Designated District Hospital, Muheza, Tanzania (E.K., M.F., P.E.D.).
authors.forename: Bronner P
authors.initials: BP
authors.lastname: Gonçalves
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Robert
authors.initials: R
authors.lastname: Morrison
authors.forename: Sarah
authors.initials: S
authors.lastname: Holte
authors.forename: Edward
authors.initials: E
authors.lastname: Kabyemela
authors.forename: D Rebecca
authors.initials: DR
authors.lastname: Prevots
authors.forename: Michal
authors.initials: M
authors.lastname: Fried
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
mesh_terms: D002675:Child, Preschool; D060467:Disease Resistance; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000145:classification / Q000150:complications / Q000276:immunology / Q000469:parasitology*; D008297:Male; D059208:Parasite Load; D018512:Parasitemia; D010298:Parity; D010920:Placenta / Q000469:parasitology; D010922:Placenta Diseases; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors; D012720:Severity of Illness Index; D012805:Sickle Cell Trait / Q000150:complications*; D013636:Tanzania