Memory B-Cell Responses Against Merozoite Antigens After Acute Plasmodium falciparum Malaria, Assessed Over One Year Using a Novel Multiplexed FluoroSpot Assay

Memory B cells (MBCs) are believed to be important for the maintenance of immunity to malaria, and these cells need to be explored in the context of different parasite antigens and their breadth and kinetics after natural infections. However, frequencies of antigen-specific MBCs are low in peripheral blood, limiting the number of antigens that can be studied, especially when small blood volumes are available. Here, we developed a multiplexed reversed B-cell FluoroSpot assay capable of simultaneously detecting MBCs specific for the four Plasmodium falciparum blood-stage antigens, MSP-119, MSP-2, MSP-3 and AMA-1. We used the assay to study the kinetics of the MBC response after an acute episode of malaria and up to one year following treatment in travelers returning to Sweden from sub-Saharan Africa. We show that the FluoroSpot assay can detect MBCs to all four merozoite antigens in the same well, and that the breadth and kinetics varied between individuals. We further found that individuals experiencing a primary infection could mount and maintain parasite-specific MBCs to a similar extent as previously exposed adults, already after a single infection. We conclude that the multiplexed B-cell FluoroSpot is a powerful tool for assessing antigen-specific MBC responses to several antigens simultaneously, and that the kinetics of MBC responses against merozoite surface antigens differ over the course of one year. These findings contribute to the understanding of acquisition and maintenance of immune responses to malaria.

Download Full-text

Cost-Effectiveness of the Introduction of a Pre-Erythrocytic Malaria Vaccine into the Expanded Program on Immunization in Sub-Saharan Africa: Analysis of Uncertainties Using a Stochastic Individual-Based Simulation Model of Plasmodium falciparum Malaria

Value in Health ◽

10.1016/j.jval.2011.06.004 ◽

2011 ◽

Vol 14 (8) ◽

pp. 1028-1038 ◽

Cited By ~ 20

Author(s):

Nicolas Maire ◽

Samuel D. Shillcutt ◽

Damian G. Walker ◽

Fabrizio Tediosi ◽

Thomas A. Smith

Keyword(s):

Plasmodium Falciparum ◽

Cost Effectiveness ◽

Simulation Model ◽

Falciparum Malaria ◽

Malaria Vaccine ◽

Plasmodium Falciparum Malaria ◽

Sub Saharan Africa ◽

Sub Saharan ◽

Individual Based Simulation ◽

Expanded Program On Immunization

Download Full-text

Therapeutic Efficacy of Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Northern Ethiopia

Malaria Research and Treatment ◽

10.1155/2012/548710 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Gebremedhin Kinfu ◽

Solomon Gebre-Selassie ◽

Nigus Fikrie

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Falciparum Malaria ◽

Sub Saharan Africa ◽

Northern Ethiopia ◽

Clearance Time ◽

Inclusion Criteria ◽

Cure Rate ◽

Fever Clearance Time ◽

Sub Saharan ◽

Uncomplicated Plasmodium Falciparum Malaria

Introduction. Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. This has posed major challenges to malaria control in sub-Saharan Africa. Objective. The aim of the study was to evaluate the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in North Ethiopia. Methods. This prospective study was undertaken during August–November 2009 on 71 malaria patients that fulfilled the inclusion criteria set by the WHO. Patients were followed up for 28 days. Thick and thin blood films were prepared by Giemsa stain for microscopy to determine parasite density. A standard six-dose regimen of artemether-lumefantrine was administered over three days and was followed up with clinical and parasitological evaluations over 28 days. Results. The cure rate (ACPR) was found to be high (97.2%) in this study. The parasite and fever clearance time was also rapid. Artemether-lumefantrine for the treatment of acute uncomplicated Plasmodium falciparum malaria in the study area showed 97.2% cure rate and only 2.8% failure rate. Conclusion. The result showed that the drug could continue as first line for the treatment of uncomplicated Plasmodium falciparum malaria in the study area. The efficacy of artemether-lumefantrine needs to be carefully monitored periodically in sentinel sites representing different areas of the country.

Download Full-text

Multicentric assessment of the efficacy and tolerability of dihydroartemisinin-piperaquine compared to artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa

Malaria Journal ◽

10.1186/1475-2875-10-198 ◽

2011 ◽

Vol 10 (1) ◽

Cited By ~ 31

Author(s):

William Yavo ◽

Babacar Faye ◽

Thomas Kuete ◽

Vincent Djohan ◽

Serge A Oga ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Falciparum Malaria ◽

Plasmodium Falciparum Malaria ◽

Sub Saharan Africa ◽

Sub Saharan ◽

Uncomplicated Plasmodium Falciparum Malaria

Download Full-text

Measuring Antibody Avidity To Plasmodium Falciparum Merozoite Antigens Using A Multiplex Immunoassay Approach

10.21203/rs.2.23647/v1 ◽

2020 ◽

Author(s):

Diane Wallace Taylor ◽

Naveen Bobbili ◽

Alexander K Kayatani ◽

Samuel Tassi-Yunga ◽

Rose FG Leke

Keyword(s):

Plasmodium Falciparum ◽

Clonal Selection ◽

Ammonium Thiocyanate ◽

Plasmodium Falciparum Malaria ◽

Affinity Maturation ◽

Binding Studies ◽

Simple Method ◽

Antibody Avidity ◽

Merozoite Antigens ◽

One Year

Abstract Background: Antibodies (Ab) play a significant role in immunity to Plasmodium falciparum malaria. Usually, following repeated exposure to pathogens, affinity maturation and clonal selection take place, resulting in increased antibody avidity. However, some studies suggest affinity maturation may not take place to malaria antigens in endemic areas. Information on development of antibody avidity is confusing and conflicting, in part, because different techniques have been used to measure avidity. Today, bead-based multiplex immunoassays (MIA) are routinely used to simultaneously quantitate antibody levels to multiple antigens. This study evaluated the feasibility of developing an avidity MIA with 5 merozoite antigens (AMA1, EBA-175, MSP1-42, MSP2, MSP3) that used a single chaotropic concentration. Methods: The most common ELISA protocols that used the chaotropic reagents guanidine HCl (GdHCl), urea, and ammonium thiocyanate (NH4SCN) were adapted to a multiplex MIA format. Then, different concentrations of chaotropes and incubation times were compared and results were expressed as an Avidity Index (AI), i.e., percentage of antibody remaining bound in the presence of chaotrope. Experiments were conducted to i) identify the assay with the widest range of AI (discriminatory power), ii) determine the amount of chaotrope needed to release 50% of bound Ab using plasma from adults and infants, and iii) evaluate assay repeatability. Results: Overall, 4M GdHCl and 8M urea were weaker chaotropes than 3M NH4SCN. For example, they failed to release significant amounts of Ab bound to MSP1-42 in adult plasma samples; whereas, a range of AI values was obtained with NH4SCN. Titration of NH4SCN revealed that 2M urea gave the widest range of AI for the 5 antigens. Binding studies using plasma from 40 adults and 57 one-year old infants in Cameroon showed that 2.1M ± 0.32 (mean ± SD) NH4SCN (adults) and 1.8M ± 0.23M released 50% of bound Ab from the merozoite antigens. The final avidity multiplex assay was highly repeatable. Conclusions. An avidity MIA is feasible for the 5 merozoite antigens that uses a single concentration (2M) of NH4SCN. The assay provides a simple method to quickly obtain information about Ab quantity and quality in the acquisition of immunity to malaria in endemic populations.

Download Full-text