Standardization and validation of a cytometric bead assay to assess antibodies to multiple Plasmodium falciparum recombinant antigens

Ondigo, Bartholomew N.; Park, Gregory S.; Gose, Severin; Ho, Benjamin M; Ochola, Lyticia A; Ayodo, George; Ofulla, Ayub V.; John, Chandy C.

doi:10.1186/1475-2875-11-427

Cited by 30 publications

(37 citation statements)

References 38 publications

(40 reference statements)

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“…Additionally, dynamics of antibody acquisition and maintenance vary based on exposure intensity and age; thus, the degree to which some serologic biomarkers predict exposure will likely vary in these contexts (39,57,75,79). Our study only evaluated participants ages 3-7 y old living in two areas of Uganda with moderate or high transmission and ages 2-7 y old living in an area with intense seasonal transmission in Mali.…”

Section: Discussionmentioning

confidence: 99%

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities

Helb

Tetteh

Felgner

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

193

262

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Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates of Pf exposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf antigens by protein microarray in 186 Ugandan children, for whom detailed Pf exposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual's recent exposure. Responses to three novel Pf antigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86-0.93), whereas responses to six antigens accurately estimated an individual's malaria incidence in the prior year. Crossvalidated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISAbased assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.any countries have extensive programs to reduce the burden of Plasmodium falciparum (Pf), the parasite responsible for most malaria morbidity and mortality (1). Effectively using limited resources for malaria control or elimination and evaluating interventions require accurate measurements of the risk of being infected with Pf (2-15). To reflect the rate at which individuals are infected with Pf in a useful way, metrics used to estimate exposure in a community need to account for dynamic changes over space and time, especially in response to control interventions (16)(17)(18).A variety of metrics can be used to estimate Pf exposure, but tools that are more precise and low cost are needed for population surveillance. Existing metrics have varying intrinsic levels of precision and accuracy and are subject to a variety of extrinsic factors, such as cost, time, and availability of trained personnel (19). For example, entomological measurements provide information on mosquito to human transmission for a community but are expensive, require specially trained staff, and lack standardized procedures, all of which reduce precision and/or make interpretation difficult (19)(20)(21)(22). Parasite prevalence can be meas...

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Section: Discussionmentioning

confidence: 99%

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities

Helb

Tetteh

Felgner

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

193

262

View full text Add to dashboard Cite

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“…This has led to an increasing interest in the use of serology in acquiring epidemiological information that can be implemented in malaria control programmes [9, 13, 40, 49–55]. At this point, the majority of the studies and elimination programmes have focused in first instance on P. falciparum [13, 27, 38, 45, 46, 52, 56], which is easier to eliminate than P. vivax due to possible relapses in the latter one [57]. However, in contrast to other studies the current study was carried out in Southeast Asia (Cambodia) where all human malaria parasites are co-occurring [26, 58] and in which occupational and behavioural factors define the risk for malaria exposure [59–61].…”

Section: Discussionmentioning

confidence: 99%

Serological markers to measure recent changes in malaria at population level in Cambodia

Kerkhof

Sluydts

Willen

et al. 2016

Malar J

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BackgroundSerological markers for exposure to different Plasmodium species have recently been used in multiplex immunoassays based on the Luminex technology. However, interpretation of the assay results requires consideration of the half-life of specific antibodies against these markers. Therefore, the aim of the present study was to document the half-life of malaria specific serological makers, as well as assessing the sensitivity of these markers to pick up recent changes in malaria exposure.MethodsA recently developed multiplex immunoassay was used to measure the intensity of antibody (Ab) responses against 19 different Plasmodium specific antigens, covering different human malaria parasites and two vector saliva antigens. Therefore, 8439 blood samples from five cross-sectional surveys in Ratanakiri, Cambodia, were analysed. These involve a random selection from two selected surveys, and an additional set of blood samples of individuals that were randomly re-sampled three, four or five times. A generalized estimating equation model and linear regression models were fitted on log transformed antibody intensity data.ResultsResults showed that most (17/21) Ab-responses are higher in PCR positive than PCR negative individuals. Furthermore, these antibody-responses follow the same upward trend within each age group. Estimation of the half-lives showed differences between serological markers that reflect short- (seasonal) and long-term (year round) transmission trends. Ab levels declined significantly together with a decrease of PCR prevalence in a group of malaria endemic villages.ConclusionFor Plasmodium falciparum, antibodies against LSA3.RE, GLURP and Pf.GLURP.R2 are most likely to be a reflexion of recent (range from 6 to 8 months) exposure in the Mekong Subregion. PvEBP is the only Plasmodium vivax Ag responding reasonably well, in spite of an estimated Ab half-life of more than 1 year. The use of Ab intensity data rather dichotomizing the continuous Ab-titre data (positive vs negative) will lead to an improved approach for serological surveillance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1576-z) contains supplementary material, which is available to authorized users.

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“…Study participants with AU values .1.0 were considered antibody responders (21,22). A decline in AMA-1 reflects declining exposure to malaria (23).…”

Section: Plasmodium Falciparum Antigen Serologic Testingmentioning

confidence: 99%

“…Antibody concentrations for AMA-1 are expressed in arbitrary units (AU), which were calculated by dividing the MFI generated by the test sample by the mean MFI plus 3 SDs generated by samples from 9 North Americans never exposed to malaria (21,22). Study participants with AU values .1.0 were considered antibody responders (21,22).…”

Section: Plasmodium Falciparum Antigen Serologic Testingmentioning

confidence: 99%

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Standardization and validation of a cytometric bead assay to assess antibodies to multiple Plasmodium falciparum recombinant antigens

Cited by 30 publications

References 38 publications

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities

Serological markers to measure recent changes in malaria at population level in Cambodia

Decline in childhood iron deficiency after interruption of malaria transmission in highland Kenya , ,

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