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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

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–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.


Association between altitude or EIR and rate of seroconversion from M.RCAg-1 seronegative to seropositive. a Plot of estimated seroconversion rates(λ) (calculated as for Fig. 6) against altitude. The line and R2 value are for the least-squares fitted functionλ = 0.0534e-0.002h, where h is the altitude in m. b Plot of log(λ) against log (predicted EIR). The least-squares fitted line has the equation Log10(λ) = 0.01*Log10(EIR)-2.3653. EIR was calculated from the equation log(EIR) = 2.523–0.0025 * altitude [35]
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Fig7: Association between altitude or EIR and rate of seroconversion from M.RCAg-1 seronegative to seropositive. a Plot of estimated seroconversion rates(λ) (calculated as for Fig. 6) against altitude. The line and R2 value are for the least-squares fitted functionλ = 0.0534e-0.002h, where h is the altitude in m. b Plot of log(λ) against log (predicted EIR). The least-squares fitted line has the equation Log10(λ) = 0.01*Log10(EIR)-2.3653. EIR was calculated from the equation log(EIR) = 2.523–0.0025 * altitude [35]

Mentions: To obtain the parameter λ for each village, we calculated the seroprevalence data for each settlement stratified by age (Fig. 5), and then calculated the SCR using maximum-likelihood fits from a reversible catalytic equilibrium model (Fig. 6). Compared to the villages of Yunnan, the proportion of seroprevalence was higher in children <14 years old from Jieyangka, suggesting that the on-going Pf infection was more serious in this area. The parameter ρ was set to 0 in this study [5]. Parameter λ was 0.0128 for Jieyangka, 0.004 for Susuzhai, 0.0047 for Qiushan, and 0.043 for Kayahe. The age seroprevalence curve did not fit as well for Jieyangka as for the villages of Yunnan, showing that the observed seroprevalence in children <14 years of age was above the predicted curve. Theoretically, models should be fitted by two steps to calculate two forces of an infection profile when visual examination of the SCR suggests it is not uniform over the whole population, but finite-sized samples in this study limited further calculation. Therefore, the Pf malaria transmission in Jieyangka was underestimated here, especially in children under 14 years of age. Importantly, we identified a semi-logarithmic relationship between the village-specific rate of seroconversion (λ) and altitude, and the log (λ) linearly correlated with log (EIR), which was estimated from altitude [35] (Fig. 7).Fig. 5


Multi-epitope chimeric antigen used as a serological marker to estimate Plasmodium falciparum transmission intensity in the border area of China-Myanmar
Association between altitude or EIR and rate of seroconversion from M.RCAg-1 seronegative to seropositive. a Plot of estimated seroconversion rates(λ) (calculated as for Fig. 6) against altitude. The line and R2 value are for the least-squares fitted functionλ = 0.0534e-0.002h, where h is the altitude in m. b Plot of log(λ) against log (predicted EIR). The least-squares fitted line has the equation Log10(λ) = 0.01*Log10(EIR)-2.3653. EIR was calculated from the equation log(EIR) = 2.523–0.0025 * altitude [35]
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5015264&req=5

Fig7: Association between altitude or EIR and rate of seroconversion from M.RCAg-1 seronegative to seropositive. a Plot of estimated seroconversion rates(λ) (calculated as for Fig. 6) against altitude. The line and R2 value are for the least-squares fitted functionλ = 0.0534e-0.002h, where h is the altitude in m. b Plot of log(λ) against log (predicted EIR). The least-squares fitted line has the equation Log10(λ) = 0.01*Log10(EIR)-2.3653. EIR was calculated from the equation log(EIR) = 2.523–0.0025 * altitude [35]
Mentions: To obtain the parameter λ for each village, we calculated the seroprevalence data for each settlement stratified by age (Fig. 5), and then calculated the SCR using maximum-likelihood fits from a reversible catalytic equilibrium model (Fig. 6). Compared to the villages of Yunnan, the proportion of seroprevalence was higher in children <14 years old from Jieyangka, suggesting that the on-going Pf infection was more serious in this area. The parameter ρ was set to 0 in this study [5]. Parameter λ was 0.0128 for Jieyangka, 0.004 for Susuzhai, 0.0047 for Qiushan, and 0.043 for Kayahe. The age seroprevalence curve did not fit as well for Jieyangka as for the villages of Yunnan, showing that the observed seroprevalence in children <14 years of age was above the predicted curve. Theoretically, models should be fitted by two steps to calculate two forces of an infection profile when visual examination of the SCR suggests it is not uniform over the whole population, but finite-sized samples in this study limited further calculation. Therefore, the Pf malaria transmission in Jieyangka was underestimated here, especially in children under 14 years of age. Importantly, we identified a semi-logarithmic relationship between the village-specific rate of seroconversion (λ) and altitude, and the log (λ) linearly correlated with log (EIR), which was estimated from altitude [35] (Fig. 7).Fig. 5

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.