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Multi-epitope chimeric antigen used as a serological marker to estimate Plasmodium falciparum transmission intensity in the border area of China-Myanmar

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ABSTRACT

Background: Following the decline of malaria transmission in many countries and regions, serological parameters have become particularly useful for estimating malaria transmission in low-intensity areas. This study evaluated a novel serological marker, Malaria Random Constructed Antigen-1 (M.RCAg-1), which contains 11 epitopes from eight Plasmodium falciparum antigens, as a tool for assessing malaria transmission intensity along the border area of China-Myanmar.

Method: Serum from Plasmodium falciparum and P. vivax patients was used to detect the properties of M.RCAg-1 and antibody responses. Cross-sectional surveys were conducted at the China-Myanmar border and in Hainan province in 2012 and 2013 using cluster sampling. Filter blood spot papers were collected from all participants. Antibodies against M.RCAg-1 were detected using indirect ELISA. The Mann–Whitney test and Spearman’s rank correlation test were performed to analyze antibody data. P. falciparum malaria transmission intensity was estimated using a catalytic conversion model based on the maximum likelihood of generating a community seroconversion rate (SCR).

Results: M.RCAg-1 was well-recognized by the naturally acquired anti-malaria antibodies in P. falciparum patients and had very limited cross-reactivity with P. vivax infection. The total amount of IgG antibodies was decreased with the decrease in parasitemia after taking medication and lasted several weeks. In a population survey, the antibody levels were higher in residents living close to the China-Myanmar border than those living in non-epidemic areas (P < 0.0001), but no significant difference was observed between residents from Hainan and non-epidemic areas. The calculated SCR was 0.0128 for Jieyangka, 0.004 for Susuzhai, 0.0047 for Qiushan, and 0.043 for Kayahe. The estimated exposure rate obtained from the anti-M.RCAg-1 antibody level correlated with traditional measures of transmission intensity derived from altitude.

Conclusion: Our study demonstrates that M.RCAg-1 is potentially useful as a serological indicator of exposure to P. falciparum malaria, especially for malaria surveillance in low transmission areas.

Electronic supplementary material: The online version of this article (doi:10.1186/s40249-016-0194-x) contains supplementary material, which is available to authorized users.

No MeSH data available.


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Antibody response to M.RCAg-1 and its epitopes in serums of malaria patients. a The IgG antibody levels against M.RCAg-1in Pv, Pf malaria patients and normal controls. b The X axis was days between the date of malaria onset and the date taking treatment, the Y axis showed the antibody levels. c Antibodies to all epitopes of M.RCAg-1. d The association between parasitemia and antibody levels
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Fig2: Antibody response to M.RCAg-1 and its epitopes in serums of malaria patients. a The IgG antibody levels against M.RCAg-1in Pv, Pf malaria patients and normal controls. b The X axis was days between the date of malaria onset and the date taking treatment, the Y axis showed the antibody levels. c Antibodies to all epitopes of M.RCAg-1. d The association between parasitemia and antibody levels

Mentions: To investigate M.RCAg-1-specific antibody responses, we collected serum from malaria patients in Laza in 2008 before they took medicine (Fig. 2). The IgG antibody levels were predominantly higher in Pf patients than in Pv patients (P < 0.0001) and negative controls (P < 0.0001), and there was very limited cross-reactivity of M.RCAg-1 with Pv infection (Fig. 2a). The average antibody levels in Pf patients grouped by onset time are shown in Fig. 2b. These results suggest that anti-M.RCAg-1 antibody can be stimulated once malaria occurs and maintained at a certain concentration during the infection, though with some fluctuation. The levels of antibody to epitopes of M.RCAg-1 were also tested (Fig. 2c). All 11 epitopes could be identified to varying degrees by the naturally acquired antibodies in serum from Pf patients. A negative correlation was found between antibody levels and the parasitemia (r = -0.334, P < 0.05) in Pf patient serum (Fig. 2d), indicating that the anti- M.RCAg-1 antibodies offer immune protection against malaria.Fig. 2


Multi-epitope chimeric antigen used as a serological marker to estimate Plasmodium falciparum transmission intensity in the border area of China-Myanmar
Antibody response to M.RCAg-1 and its epitopes in serums of malaria patients. a The IgG antibody levels against M.RCAg-1in Pv, Pf malaria patients and normal controls. b The X axis was days between the date of malaria onset and the date taking treatment, the Y axis showed the antibody levels. c Antibodies to all epitopes of M.RCAg-1. d The association between parasitemia and antibody levels
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC5015264&req=5

Fig2: Antibody response to M.RCAg-1 and its epitopes in serums of malaria patients. a The IgG antibody levels against M.RCAg-1in Pv, Pf malaria patients and normal controls. b The X axis was days between the date of malaria onset and the date taking treatment, the Y axis showed the antibody levels. c Antibodies to all epitopes of M.RCAg-1. d The association between parasitemia and antibody levels
Mentions: To investigate M.RCAg-1-specific antibody responses, we collected serum from malaria patients in Laza in 2008 before they took medicine (Fig. 2). The IgG antibody levels were predominantly higher in Pf patients than in Pv patients (P < 0.0001) and negative controls (P < 0.0001), and there was very limited cross-reactivity of M.RCAg-1 with Pv infection (Fig. 2a). The average antibody levels in Pf patients grouped by onset time are shown in Fig. 2b. These results suggest that anti-M.RCAg-1 antibody can be stimulated once malaria occurs and maintained at a certain concentration during the infection, though with some fluctuation. The levels of antibody to epitopes of M.RCAg-1 were also tested (Fig. 2c). All 11 epitopes could be identified to varying degrees by the naturally acquired antibodies in serum from Pf patients. A negative correlation was found between antibody levels and the parasitemia (r = -0.334, P < 0.05) in Pf patient serum (Fig. 2d), indicating that the anti- M.RCAg-1 antibodies offer immune protection against malaria.Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

Background: Following the decline of malaria transmission in many countries and regions, serological parameters have become particularly useful for estimating malaria transmission in low-intensity areas. This study evaluated a novel serological marker, Malaria Random Constructed Antigen-1 (M.RCAg-1), which contains 11 epitopes from eight Plasmodium falciparum antigens, as a tool for assessing malaria transmission intensity along the border area of China-Myanmar.

Method: Serum from Plasmodium falciparum and P. vivax patients was used to detect the properties of M.RCAg-1 and antibody responses. Cross-sectional surveys were conducted at the China-Myanmar border and in Hainan province in 2012 and 2013 using cluster sampling. Filter blood spot papers were collected from all participants. Antibodies against M.RCAg-1 were detected using indirect ELISA. The Mann&ndash;Whitney test and Spearman&rsquo;s rank correlation test were performed to analyze antibody data. P. falciparum malaria transmission intensity was estimated using a catalytic conversion model based on the maximum likelihood of generating a community seroconversion rate (SCR).

Results: M.RCAg-1 was well-recognized by the naturally acquired anti-malaria antibodies in P. falciparum patients and had very limited cross-reactivity with P. vivax infection. The total amount of IgG antibodies was decreased with the decrease in parasitemia after taking medication and lasted several weeks. In a population survey, the antibody levels were higher in residents living close to the China-Myanmar border than those living in non-epidemic areas (P&thinsp;&lt;&thinsp;0.0001), but no significant difference was observed between residents from Hainan and non-epidemic areas. The calculated SCR was 0.0128 for Jieyangka, 0.004 for Susuzhai, 0.0047 for Qiushan, and 0.043 for Kayahe. The estimated exposure rate obtained from the anti-M.RCAg-1 antibody level correlated with traditional measures of transmission intensity derived from altitude.

Conclusion: Our study demonstrates that M.RCAg-1 is potentially useful as a serological indicator of exposure to P. falciparum malaria, especially for malaria surveillance in low transmission areas.

Electronic supplementary material: The online version of this article (doi:10.1186/s40249-016-0194-x) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus