Force of infection is key to understanding the epidemiology of<i>Plasmodium falciparum</i>malaria in Papua New Guinean children

Müeller, Ivo; Schoepflin, Sonja; Smith, T.; Benton, Kathryn; Bretscher, Michael T.; Lin, Enmoore; Kiniboro, Benson; Zimmerman, Peter A.; Speed, Terence P.; Siba, Peter; Felger, Ingrid

doi:10.1073/pnas.1200841109

Cited by 111 publications

(166 citation statements)

References 47 publications

Supporting

Mentioning

154

Contrasting

Order By: Relevance

“…Heterogeneity in P. falciparum transmission intensity exists, even within small geographical areas, and this may lead to differences in malaria exposure (32). In this study, we used a novel molecular marker of exposure in the cohort, mol FOI, and examined its relationship to antibody levels and associations with malaria risk.…”

Section: Figmentioning

confidence: 99%

“…High polymorphism of this marker was observed in this study population, with 52 different MSP2 genotypes identified (47). A new infection was defined as any MSP2 genotype detected in a given 8-week interval that was not detected during the previous interval, and the number of infections with new genotypes was calculated for each individual (32). Genotyping was undertaken on blood samples collected during both the morbidity surveillance and the 8 periods of weekly active surveillance.…”

Section: Study Populationmentioning

confidence: 99%

“…Samples from scheduled bleeds as well as morbidity surveillance were used. The force of infection for each child and interval was defined as the number of new clones acquired per year at risk (i.e., the molecular force of infection) and was cube-root transformed (32).…”

Section: Study Populationmentioning

confidence: 99%

“…The molecular force of infection ( mol FOI) was used to define the number of new P. falciparum clones acquired during the study follow-up period. The mol FOI was determined using previously described methods (32). Briefly, DNA samples were genotyped for merozoite surface protein 2 (MSP2) using capillary electrophoresis for fragment sizing as described in reference 46 with minor modifications (47).…”

Section: Study Populationmentioning

confidence: 99%

“…Understanding how these factors influence functional immunity is important for defining key targets of immunity; however, addressing these issues is challenging and new approaches and insights are needed. A recent study used a novel molecular method to define the number of new P. falciparum clones acquired over time (the molecular force of infection [ mol FOI]) (32) and demonstrated a strong relationship between this parameter and factors that influence heterogeneity in exposure within a population (e.g., seasonality, location, and the use of bed nets). Furthermore, mol FOI, as a marker of an individual's exposure to malaria, was the major predictor of clinical disease in a cohort of young children still actively acquiring immunity to P. falciparum (32).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Acquisition of Antibodies against Plasmodium falciparum Merozoites and Malaria Immunity in Young Children and the Influence of Age, Force of Infection, and Magnitude of Response

et al. 2015

Self Cite

View full text Add to dashboard Cite

i Individuals in areas of Plasmodium falciparum endemicity develop immunity to malaria after repeated exposure. Knowledge of the acquisition and nature of protective immune responses to P. falciparum is presently limited, particularly for young children. We examined antibodies (IgM, IgG, and IgG subclasses) to merozoite antigens and their relationship to the prospective risk of malaria in children 1 to 4 years of age in a region of malaria endemicity in Papua New Guinea. IgG, IgG1, and IgG3 responses generally increased with age, were higher in children with active infection, and reflected geographic heterogeneity in malaria transmission. Antigenic properties, rather than host factors, appeared to be the main determinant of the type of IgG subclass produced. High antibody levels were not associated with protection from malaria; in contrast, they were typically associated with an increased risk of malaria. Adjustment for malaria exposure, using a novel molecular measure of the force of infection by P. falciparum, accounted for much of the increased risk, suggesting that the antibodies were markers of higher exposure to P. falciparum. Comparisons between antibodies in this cohort of young children and in a longitudinal cohort of older children suggested that the lack of protective association was explained by lower antibody levels among young children and that there is a threshold level of antibodies required for protection from malaria. Our results suggest that in populations with low immunity, such as young children, antibodies to merozoite antigens may act as biomarkers of malaria exposure and that, with increasing exposure and responses of higher magnitude, antibodies may act as biomarkers of protective immunity. In areas of malaria endemicity, immunity that protects from high (H)-density parasitemia and symptomatic disease develops over a number of years (1). Knowledge of the precise nature of the protective immune responses to Plasmodium falciparum, in terms of the immune mechanisms, the specific target antigens, the nature of responses, and the rate of acquisition of immunity, has been sought, and while advances have been made, our current understanding is still limited (2, 3). Past experiments involving the passive transfer of immunoglobulin from immune adults into P. falciparum-infected individuals provided strong evidence that antibodies (Abs) play an important role in mediating immunity and target the blood stages of infection (4-6). Targets of antibodies include antigens expressed by the merozoite stage of the parasite, and these antibodies function by inhibiting merozoite invasion of red blood cells and by opsonizing merozoites for uptake by phagocytes and antibody-dependent cellular inhibition (7)(8)(9)(10)(11)(12)(13)(14).An important approach for identifying antigens as targets of protective immunity in humans is to assess the acquisition of antibodies and the association between antigen-specific responses and protection from symptomatic malaria in malariaexposed populations (3), particularly in lo...

show abstract

Section: Figmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations