Faculty Opinions recommendation of IgG antibody responses to Plasmodium falciparum merozoite antigens in Kenyan children have a short half-life.

Author(s):  
James Beeson
2020 ◽  
Author(s):  
Victor Yman ◽  
James Tuju ◽  
Michael T White ◽  
Gathoni Kamuyu ◽  
Kennedy Mwai ◽  
...  

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could dramatically improve current surveillance methods by allowing for accurate estimates of infection incidence from limited data. We studied the IgG antibody response to 111 Plasmodium falciparum proteins in travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a novel combination of five serological markers (GAMA, MSP1, MSPDBL1 C- and N-terminal, and PfSEA1) that detect exposure within the previous 3-months with >80% sensitivity and specificity. Using mathematical modelling, we examined the antibody kinetics and determined that responses informative of recent exposure display several distinct characteristics: rapid initial boosting and decay, less inter-individual variation in response kinetics, and minimal persistence over time. These serological exposure markers can be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination.


2013 ◽  
Vol 20 (8) ◽  
pp. 1170-1180 ◽  
Author(s):  
Hodan Ahmed Ismail ◽  
Ulf Ribacke ◽  
Linda Reiling ◽  
Johan Normark ◽  
Tom Egwang ◽  
...  

ABSTRACTMalaria can present itself as an uncomplicated or severe disease. We have here studied the quantity and quality of antibody responses against merozoite antigens, as well as multiplicity of infection (MOI), in children from Uganda. We found higher levels of IgG antibodies toward erythrocyte-binding antigen EBA181, MSP2 ofPlasmodium falciparum3D7 and FC27 (MSP2-3D7/FC27), and apical membrane antigen 1 (AMA1) in patients with uncomplicated malaria by enzyme-linked immunosorbent assay (ELISA) but no differences against EBA140, EBA175, MSP1, and reticulocyte-binding protein homologues Rh2 and Rh4 or for IgM against MSP2-3D7/FC27.Patients with uncomplicated malaria were also shown to have higher antibody affinities for AMA1 by surface plasmon resonance (SPR). Decreased invasion of two clinicalP. falciparumisolates in the presence of patient plasma correlated with lower initial parasitemia in the patients, in contrast to comparisons of parasitemia to ELISA values or antibody affinities, which did not show any correlations. Analysis of the heterogeneity of the infections revealed a higher MOI in patients with uncomplicated disease, with theP. falciparumK1 MSP1 (MSP1-K1) and MSP2-3D7 being the most discriminative allelic markers. Higher MOIs also correlated positively with higher antibody levels in several of the ELISAs. In conclusion, certain antibody responses and MOIs were associated with differences between uncomplicated and severe malaria. When different assays were combined, some antibodies, like those against AMA1, seemed particularly discriminative. However, only decreased invasion correlated with initial parasitemia in the patient, signaling the importance of functional assays in understanding development of immunity against malaria and in evaluating vaccine candidates.


2021 ◽  
Vol 11 ◽  
Author(s):  
Brian R. Omondi ◽  
Michelle K. Muthui ◽  
William I. Muasya ◽  
Benedict Orindi ◽  
Ramadhan S. Mwakubambanya ◽  
...  

BackgroundMalaria caused by Plasmodium falciparum remains a serious global public health challenge especially in Africa. Interventions that aim to reduce malaria transmission by targeting the gametocyte reservoir are key to malaria elimination and/or eradication. However, factors that are associated with gametocyte carriage have not been fully explored. Consequently, identifying predictors of the infectious reservoir is fundamental in the elimination campaign.MethodsWe cultured P. falciparum NF54 gametocytes (to stage V) and prepared crude gametocyte extract. Samples from a total of 687 participants (aged 6 months to 67 years) representing two cross-sectional study cohorts in Kilifi, Kenya were used to assess IgG antibody responses by ELISA. We also analyzed IgG antibody responses to the blood-stage antigen AMA1 as a marker of asexual parasite exposure. Gametocytemia and asexual parasitemia data quantified by microscopy and molecular detection (QT-NASBA) were used to determine the relationship with antibody responses, season, age, and transmission setting. Multivariable logistic regression models were used to study the association between antibody responses and gametocyte carriage. The predictive power of the models was tested using the receiver operating characteristic (ROC) curve.ResultsMultivariable logistic regression analysis showed that IgG antibody response to crude gametocyte extract predicted both microscopic (OR=1.81 95% CI: 1.06–3.07, p=0.028) and molecular (OR=1.91, 95% CI: 1.11–3.29, p=0.019) P. falciparum gametocyte carriage. Antibody responses to AMA1 were also associated with both microscopic (OR=1.61 95% CI: 1.08–2.42, p=0.020) and molecular (OR=3.73 95% CI: 2.03–6.74, p<0.001) gametocytemia. ROC analysis showed that molecular (AUC=0.897, 95% CI: 0.868–0.926) and microscopic (AUC=0.812, 95% CI: 0.758–0.865) multivariable models adjusted for gametocyte extract showed very high predictive power. Molecular (AUC=0.917, 95% CI: 0.891–0.943) and microscopic (AUC=0.806, 95% CI: 0.755–0.858) multivariable models adjusted for AMA1 were equally highly predictive.ConclusionIn our study, it appears that IgG responses to crude gametocyte extract are not an independent predictor of gametocyte carriage after adjusting for AMA1 responses but may predict gametocyte carriage as a proxy marker of exposure to parasites. Serological responses to AMA1 or to gametocyte extract may facilitate identification of individuals within populations who contribute to malaria transmission and support implementation of transmission-blocking interventions.


2005 ◽  
Vol 73 (1) ◽  
pp. 422-430 ◽  
Author(s):  
Alfred Cortés ◽  
Mata Mellombo ◽  
Rosella Masciantonio ◽  
Vince J. Murphy ◽  
John C. Reeder ◽  
...  

ABSTRACT Antibody responses against proteins located on the surface or in the apical organelles of merozoites are presumed to be important components of naturally acquired protective immune responses against the malaria parasite Plasmodium falciparum. However, many merozoite antigens are highly polymorphic, and antibodies induced against one particular allelic form might not be effective in controlling growth of parasites expressing alternative forms. The apical membrane antigen 1 (AMA1) is a polymorphic merozoite protein that is a target of naturally acquired invasion-inhibitory antibodies and is a leading asexual-stage vaccine candidate. We characterized the antibody responses against AMA1 in 262 individuals from Papua New Guinea exposed to malaria by using different allelic forms of the full AMA1 ectodomain and some individual subdomains. The majority of individuals had very high levels of antibodies against AMA1. The prevalence and titer of these antibodies increased with age. Although antibodies against conserved regions of the molecule were predominant in the majority of individuals, most plasma samples also contained antibodies directed against polymorphic regions of the antigen. In a few individuals, predominantly from younger age groups, the majority of antibodies against AMA1 were directed against polymorphic epitopes. The D10 allelic form of AMA1 apparently contains most if not all of the epitopes present in the other allelic forms tested, which might argue for its inclusion in future AMA1-based vaccines to be tested. Some important epitopes in AMA1 involved residues located in domain II or III but depended on more than one domain.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Lamine Mahaman Moustapha ◽  
Rafiou Adamou ◽  
Maman Laminou Ibrahim ◽  
Mariama Abdoulaye Louis Padounou ◽  
Abdoulaye Diallo ◽  
...  

Abstract Background In endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in West African young children. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. This paper evaluates the effect of SMC with SPAQ on antibody concentration in young children from Niger. Methods This research was conducted in areas benefitting from SMC since 2014 (Zinder district), without SMC (Dosso district), and with 1 year of SMC since 2016 (Gaya district). To assess the relationship between SMC and Plasmodium falciparum IgG antibody responses, the total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3 to 59 months across the three areas were compared. Antibody concentrations are quantified using an enzyme-linked immunosorbent assay on the elution extracted from positive and negative malaria Rapid Diagnostic Test cassettes. Results The analysis concerns two hundred and twenty-nine children aged from 3 to 59 months: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP = 17.5 µg/ml and GLURP-R2 = 14.3 µg/ml) median antibody concentration observed are higher than in Gaya (CSP = 7.7 µg/ml and GLURP-R2 = 6.5 µg/ml) and Dosso (CSP = 4.5 µg/ml and GLURP-R2 = 3.6 µg/ml) (p < 0.0001). Conclusion The research reveals some evidences which show that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of P. falciparum infections in Niger. Increased antibody titres with increased SMC/SPAQ implementation. This contradicts hypothesis that SMC/SPAQ could reduce immunity to erythrocyte and liver-stage antigens. Further studies are necessary to provide better understanding of the SMC effect on malaria immunity.


Author(s):  
YAMMAN-USMAN HADIJAH ◽  
OMALU CJ INNOCENT ◽  
ABUBAKAR ABDULKADIR ◽  
ABOLARINWA SO ◽  
EKE S SAMUEL ◽  
...  

Objective: A cross-sectional study was carried out in a representative cohort of children in Minna aged 6 months–17 years to determine the correlation between immunoglobulin G (IgG) antibody responses to Plasmodium falciparum merozoite antigens. Methods: Plasma samples from 93 children were exposed to Enzyme-Linked Immunosorbent Assay for the measurement of IgG antibody production against P. falciparum. Results: There was a high seroprevalence of IgG antibody against P. falciparum antigens tested with 74.20%. The seroprevalence for the male category was quite higher as compared with that of the female category, though, analysis using Mann–Whitney U-test revealed IgG antibody response to P. falciparum infection in the male was significantly different as compared to the female category (p<0.05). Furthermore, the prevalence of IgG antibody against P. falciparum antigen increased with age, with the lowest observed in 6 months–5 years 66.66%. Kruskal–Wallis H test showed a non-significant difference in the production of IgG antibody against P. falciparum antigen between different cohorts, and no correlation exists between them (p>0.05). An evidence of more than 50% was found for the production of IgG antibody by sub-microscopic parasite. On the other hand, microscopically positive P. falciparum samples recorded more seroprevalence of 68.81% as against negative samples, though significant difference between the negative and positive P. falciparum infected samples and the production of IgG antibody was not observed (p>0.05). Conclusion: This study has demonstrated a boosting immune responses by sub-microscopic parasite and also suggests a strong relationship between production of IgG antibody and malaria transmission, rather than protective immunity.


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