Estimation of Recent and Long-Term Malaria Transmission in a Population by Antibody Testing to Multiple Plasmodium falciparum Antigens

Ondigo, Bartholomew N.; Hodges, James S.; Ireland, Kathleen F.; Magak, Ng’wena Gideon; Lanar, David E.; Dutta, Sandeep; Narum, David L.; Park, Gregory S.; Ofulla, Ayub V.; John, Chandy C.

doi:10.1093/infdis/jiu225

Cited by 57 publications

(69 citation statements)

References 35 publications

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“…37 This was supported by recent data from another study in Nandi that suggests that the half-lives of MSP1 antibodies in older children and adults can be on the order of decades. 38 Our work is consistent with these findings, supporting the notion that antimalarial antibody titers could be used as a surrogate of past exposure history in children and a tool for monitoring malaria control programs. [39][40][41] Although we were underpowered to detect significant changes in cellular immune responses in most cases, some trends did emerge in our analysis.…”

Section: Discussionsupporting

confidence: 87%

Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Bowman¹,

Juliano²,

Snider³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Naturally acquired immunity to Plasmodium falciparum presents a changing landscape as malaria control programs and vaccine initiatives are implemented. Determining which immunologic indicators remain surrogates of past infection, as opposed to mediators of protection, led us to compare stability of immune responses across regions with divergent malaria transmission intensities. A repeat cross-sectional study of Kenyan children from a malariaholoendemic area and an epidemic-prone area was used to examine longitudinal antibody and interferon-gamma (IFN-γ) responses to the 3D7 and FVO variants of merozoite surface protein 1 (MSP1). Antibodies to MSP1 were common in both study populations and did not significantly wane over a 21-month time period. IFN-γ responses were less frequent and rapidly disappeared in children after a prolonged period of no malaria transmission. Antibody and IFN-γ responses rarely correlated with each other; however, MSP1-specific IFN-γ response correlated with lack of concurrent P. falciparum parasitemia of the same genotype, though only statistically significantly in the malaria-holoendemic region (odds ratio = 0.31, 95% confidence interval = 0.12-0.84). This study affirms that antimalarial antibodies are informative for evaluation of history of malaria exposure within individuals, whereas cell-mediated immunity, though short lived under natural exposure conditions, might provide an assessment of recent infection and protection from parasitemia.

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Section: Discussionsupporting

confidence: 87%

Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Bowman¹,

Juliano²,

Snider³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…The P. falciparum antigens MSP-1 and AMA-1 have been used extensively in malaria serological studies, 11,[17][18][19][20] and are both thought to induce IgG antibody responses which would be present for long periods of time following infection. 10,21 For this cohort of Malian children, we found the MFI-bg signal intensities for each of these antigens to be highly skewed, with the distinct possibility of having a high titer for one of these antigens and not for the other (Figure 2). However, the antibody signal intensities for these two antigens were found to be correlated for the overall population of children (Spearman's rank correlation coefficient: ρ = 0.493, P < 0.0001).…”

Section: Resultsmentioning

confidence: 91%

Evaluation of Immunoglobulin G Responses to Plasmodium falciparum and Plasmodium vivax in Malian School Children Using Multiplex Bead Assay

Rogier¹,

Moss²,

Chard³

et al. 2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Malaria serology through assaying for IgG against Plasmodium spp. antigens provides evidence into the infection history for an individual. The multiplex bead assay (MBA) allows for detection of IgG against multiple Plasmodium spp., and can be especially useful in many regions where Plasmodium falciparum is of primary clinical focus, but other species are co-endemic. Dried blood spots were collected from 805 Malian children attending 42 elementary schools in the regions of Mopti, Sikasso, Koulikoro, and Bamako capital district, and IgG assayed by MBA. As southern Mali is known to be holoendemic for P. falciparum, merozoite surface protein 1 19-kDa subunit (MSP-1 42 ) and apical membrane antigen 1 (AMA-1) antigens were included for serology against this parasite. Responses to these antigens both provided high estimates for lifetime exposure, with 730 (90%) children with IgG antibodies for MSP-1 42 , 737 (91%) for AMA-1, and 773 (96%) positive for either or both. Also included was the antigen Plasmodium vivax MSP-1 19 , against which 140 (17.4%) children were found to have antibodies. Increases in antibody titers with older age were clearly seen with the P. falciparum antigens, but not with the P. vivax antigen, likely indicating more of a sporadic, rather than sustained transmission for this species. The MBA provides effective opportunities to evaluate malaria transmission through serological analysis for multiple Plasmodium species.

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“…Even though, limited information on the Abs persistence is available, some studies have previously estimated Ab half-lives [18, 20]. A study performed by Drakeley et al [40] found a very long half-life of 49.8 years for Abs against Pv.MSP1.19, and Ondigo et al [67] found half-lives from <1 year (3 Ags) to moderate (5–20 years for 3 Ags) and very long (>40 years for 5 Ags) by means of the threshold approach. Wipasa et al [18] and Fowkes et al [20] found a clearance of approximately 7.6 years [18] and 0.8–7.6 years [20], respectively, through linear regression models for the same Abs.…”

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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Estimation of Recent and Long-Term Malaria Transmission in a Population by Antibody Testing to Multiple Plasmodium falciparum Antigens

Cited by 57 publications

References 35 publications

Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Evaluation of Immunoglobulin G Responses to Plasmodium falciparum and Plasmodium vivax in Malian School Children Using Multiplex Bead Assay

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

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