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Failure to respond to the surface of Plasmodium falciparum infected erythrocytes predicts susceptibility to clinical malaria amongst African children.

Mackintosh CL, Mwangi T, Kinyanjui SM, Mosobo M, Pinches R, Williams TN, Newbold CI, Marsh K - Int. J. Parasitol. (2008)

Bottom Line: Following infection with Plasmodium falciparum malaria, children in endemic areas develop antibodies specific to antigens on the parasite-infected red cell surface of the infecting isolate, antibodies associated with protection against subsequent infection with that isolate.By categorising individuals according to their pre-season parasite status and antibody response to the surface of erythrocytes infected with four parasite isolates we were able to identify a group of children, those who failed to make a concomitant antibody response in the presence of an asymptomatic parasitaemia, at increased susceptibility to clinical malaria in the subsequent 6 months.Identification of this target will significantly aid understanding of naturally acquired immunity to clinical malaria amongst children in endemic areas.

View Article: PubMed Central - PubMed

Affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research Coast, Kilifi District Hospital, Kilifi, Kenya. c.mackintosh@talk21.com

ABSTRACT
Following infection with Plasmodium falciparum malaria, children in endemic areas develop antibodies specific to antigens on the parasite-infected red cell surface of the infecting isolate, antibodies associated with protection against subsequent infection with that isolate. In some circumstances induction of antibodies to heterologous parasite isolates also occurs and this has been suggested as evidence for cross-reactivity of responses against the erythrocyte surface. The role of these relatively cross-reactive antibodies in protection from clinical malaria is currently unknown. We studied the incidence of clinical malaria amongst children living on the coast of Kenya through one high transmission season. By categorising individuals according to their pre-season parasite status and antibody response to the surface of erythrocytes infected with four parasite isolates we were able to identify a group of children, those who failed to make a concomitant antibody response in the presence of an asymptomatic parasitaemia, at increased susceptibility to clinical malaria in the subsequent 6 months. The fact that this susceptible group was identified regardless of the parasite isolate tested infers a cross-reactive or conserved target is present on the surface of infected erythrocytes. Identification of this target will significantly aid understanding of naturally acquired immunity to clinical malaria amongst children in endemic areas.

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Related in: MedlinePlus

Kaplan–Meier survival curves according to antibody and parasite status. Graphs show the proportion of individuals remaining free from clinical malaria over time (days). Individuals are categorised according to whether they scored positive for antibody recognition of each parasite line in turn (dashed lines) or negative (solid lines)and whether or not they had microscopically detectable parasites at the time of the cross-sectional bleed. (A) and (B) Antibody responses measured against A4U; (C) and (D) antibody responses measured against A4 40-cycle; (E) and (F) antibody responses measured against 3D7; and (G) and (H) antibody responses measured against the clinical isolate P1. ∗∗P < 0.005 (logrank);∗P < 0.05 (logrank); ns not significant.
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fig2: Kaplan–Meier survival curves according to antibody and parasite status. Graphs show the proportion of individuals remaining free from clinical malaria over time (days). Individuals are categorised according to whether they scored positive for antibody recognition of each parasite line in turn (dashed lines) or negative (solid lines)and whether or not they had microscopically detectable parasites at the time of the cross-sectional bleed. (A) and (B) Antibody responses measured against A4U; (C) and (D) antibody responses measured against A4 40-cycle; (E) and (F) antibody responses measured against 3D7; and (G) and (H) antibody responses measured against the clinical isolate P1. ∗∗P < 0.005 (logrank);∗P < 0.05 (logrank); ns not significant.

Mentions: As a result of the interaction between parasite status and antibody recognition of each isolate, all individuals were categorised into four groups according to both their pre-season antibody status (positive or negative) and whether or not they had a microscopically detectable parasitaemia. Kaplan–Meier survival curves were drawn with each of the four groups using responses against each isolate in turn. It is clear that for responses against three of the parasite isolates tested, those individuals with asymptomatic parasite carriage and no concomitant antibody response appeared to be highly susceptible to mild clinical malaria (Fig. 2).


Failure to respond to the surface of Plasmodium falciparum infected erythrocytes predicts susceptibility to clinical malaria amongst African children.

Mackintosh CL, Mwangi T, Kinyanjui SM, Mosobo M, Pinches R, Williams TN, Newbold CI, Marsh K - Int. J. Parasitol. (2008)

Kaplan–Meier survival curves according to antibody and parasite status. Graphs show the proportion of individuals remaining free from clinical malaria over time (days). Individuals are categorised according to whether they scored positive for antibody recognition of each parasite line in turn (dashed lines) or negative (solid lines)and whether or not they had microscopically detectable parasites at the time of the cross-sectional bleed. (A) and (B) Antibody responses measured against A4U; (C) and (D) antibody responses measured against A4 40-cycle; (E) and (F) antibody responses measured against 3D7; and (G) and (H) antibody responses measured against the clinical isolate P1. ∗∗P < 0.005 (logrank);∗P < 0.05 (logrank); ns not significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2697313&req=5

fig2: Kaplan–Meier survival curves according to antibody and parasite status. Graphs show the proportion of individuals remaining free from clinical malaria over time (days). Individuals are categorised according to whether they scored positive for antibody recognition of each parasite line in turn (dashed lines) or negative (solid lines)and whether or not they had microscopically detectable parasites at the time of the cross-sectional bleed. (A) and (B) Antibody responses measured against A4U; (C) and (D) antibody responses measured against A4 40-cycle; (E) and (F) antibody responses measured against 3D7; and (G) and (H) antibody responses measured against the clinical isolate P1. ∗∗P < 0.005 (logrank);∗P < 0.05 (logrank); ns not significant.
Mentions: As a result of the interaction between parasite status and antibody recognition of each isolate, all individuals were categorised into four groups according to both their pre-season antibody status (positive or negative) and whether or not they had a microscopically detectable parasitaemia. Kaplan–Meier survival curves were drawn with each of the four groups using responses against each isolate in turn. It is clear that for responses against three of the parasite isolates tested, those individuals with asymptomatic parasite carriage and no concomitant antibody response appeared to be highly susceptible to mild clinical malaria (Fig. 2).

Bottom Line: Following infection with Plasmodium falciparum malaria, children in endemic areas develop antibodies specific to antigens on the parasite-infected red cell surface of the infecting isolate, antibodies associated with protection against subsequent infection with that isolate.By categorising individuals according to their pre-season parasite status and antibody response to the surface of erythrocytes infected with four parasite isolates we were able to identify a group of children, those who failed to make a concomitant antibody response in the presence of an asymptomatic parasitaemia, at increased susceptibility to clinical malaria in the subsequent 6 months.Identification of this target will significantly aid understanding of naturally acquired immunity to clinical malaria amongst children in endemic areas.

View Article: PubMed Central - PubMed

Affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research Coast, Kilifi District Hospital, Kilifi, Kenya. c.mackintosh@talk21.com

ABSTRACT
Following infection with Plasmodium falciparum malaria, children in endemic areas develop antibodies specific to antigens on the parasite-infected red cell surface of the infecting isolate, antibodies associated with protection against subsequent infection with that isolate. In some circumstances induction of antibodies to heterologous parasite isolates also occurs and this has been suggested as evidence for cross-reactivity of responses against the erythrocyte surface. The role of these relatively cross-reactive antibodies in protection from clinical malaria is currently unknown. We studied the incidence of clinical malaria amongst children living on the coast of Kenya through one high transmission season. By categorising individuals according to their pre-season parasite status and antibody response to the surface of erythrocytes infected with four parasite isolates we were able to identify a group of children, those who failed to make a concomitant antibody response in the presence of an asymptomatic parasitaemia, at increased susceptibility to clinical malaria in the subsequent 6 months. The fact that this susceptible group was identified regardless of the parasite isolate tested infers a cross-reactive or conserved target is present on the surface of infected erythrocytes. Identification of this target will significantly aid understanding of naturally acquired immunity to clinical malaria amongst children in endemic areas.

Show MeSH
Related in: MedlinePlus