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A Multiplex Serological Assay for the Detection of Antibody Responses to Arboviruses

Arthropod borne viruses (arboviruses) are a group of mosquito-borne pathogens that are globally distributed. Since the 2016 outbreak of Zika virus (ZIKV) ...

Institut Pasteur de Dakar

Liver-stage antigen 3 (LSA-3) is a new vaccine candidate that can induce protection against Plasmodium falciparum sporozoite challenge. Using a series of long synthetic peptides (LSP) encompassing most of the 210-kDa LSA-3 protein, a study of the antigenicity of this protein was carried out in 203 inhabitants from the villages of Dielmo (n = 143) and Ndiop (n = 60) in Senegal (the level of malaria transmission differs in these two villages). Lymphocyte responses to each individual LSA-3 peptide were recorded, some at high prevalences (up to 43%). Antibodies were also detected to each of the 20 peptides, many at high prevalence (up to 84% of responders), and were directed to both nonrepeat and repeat regions. Immune responses to LSA-3 were detectable even in individuals of less than 5 years of age and increased with age and hence exposure to malaria, although they were not directly related to the level of malaria transmission. Thus, several valuable T- and B-cell epitopes were characterized all along the LSA-3 protein, supporting the antigenicity of this P. falciparum vaccine candidate. Finally, antibodies specific for peptide LSP10 located in a nonrepeat region of LSA-3 were found significantly associated with a lower risk of malaria attack over 1 year of daily clinical follow-up in children between the ages of 7 and 15 years, but not in older individuals.

Evidence for multiple B- and T-cell epitopes in Plasmodium falciparum liver-stage antigen 3.

Programmes of pre-elimination of malaria have been implemented in Senegal since 2010, and the burden of malaria has decreased substantially. These changes in the epidemiology should be monitored with effective tools that allow changes in patterns of transmission to be estimated. In Dielmo and Ndiop, two villages of Senegal with different malaria endemicity, infections have been followed longitudinally for 20 years, during which time there have been several control interventions leading to substantial decreases of transmission. This study aimed to compare malaria antibody responses of the inhabitants of these two villages, between 2000 and 2010, using schizont crude extracts of a local strain of P. falciparum (Pf Sch07/03).

Dramatic declines in seropositivity as determined with crude extracts of Plasmodium falciparum schizonts between 2000 and 2010 in Dielmo and Ndiop, Senegal.

A better understanding of the effect of malaria control interventions on vector and parasite populations, acquired immunity, and burden of the disease is needed to guide strategies to eliminate malaria from highly endemic areas. We monitored and analysed the changes in malaria epidemiology in a village community in Senegal, west Africa, over 22 years.

The rise and fall of malaria in a West African rural community, Dielmo, Senegal, from 1990 to 2012: a 22 year longitudinal study.

Although the burden of malaria has significantly declined in recent years in sub-Saharan Africa through the widespread use of long-lasting insecticide treated bed-nets (LLINs) and artemisinin-based combination therapy, resurgence of malaria is observed in some settings after several years of LLINs use. This study aimed to assess if LLINs use remains protective against malaria during a period of resurgence of malaria morbidity in Dielmo, a rural village of Senegal.

The implication of long-lasting insecticide-treated net use in the resurgence of malaria morbidity in a Senegal malaria endemic village in 2010-2011.

Malaria in Senegal is due essentially to infections by Plasmodium falciparum and, to a lesser extent to Plasmodium malariae and Plasmodium ovale. By the use of molecular methods, detection of Plasmodium vivax has been recently reported in the region of Kedougou, raising the question of appraisal of its potential prevalence in this setting.

Unexpected high circulation of Plasmodium vivax in asymptomatic children from Kédougou, southeastern Senegal.

Dramatic changes in transmission intensity can impact Plasmodium population diversity. Using samples from 2 distant time-points in the Dielmo/Ndiop longitudinal cohorts from Senegal, we applied a molecular barcode tool to detect changes in parasite genotypes and complexity of infection that corresponded to changes in transmission intensity. We observed a striking statistically significant difference in genetic diversity between the 2 parasite populations. Furthermore, we identified a genotype in Dielmo and Ndiop previously observed in Thiès, potentially implicating imported malaria. This genetic surveillance study validates the molecular barcode as a tool to assess parasite population diversity changes and track parasite genotypes.

Dramatic Changes in Malaria Population Genetic Complexity in Dielmo and Ndiop, Senegal, Revealed Using Genomic Surveillance.

Correction to: Fine-scale Spatiotemporal Mapping of Asymptomatic and Clinical Plasmodium falciparum Infections: Epidemiological Evidence for Targeted Malaria Elimination Interventions.

Despite significant progress in malaria control over the past twenty years, malaria remains a leading cause of child morbidity and mortality in Tropical Africa. As most patients do not consult any health facility much uncertainty persists about the true burden of the disease and the range of individual differences in susceptibility to malaria.

One hundred malaria attacks since birth. A longitudinal study of African children and young adults exposed to high malaria transmission.

In low malaria transmission areas, the elimination of the disease has been hampered partly by the existence of a reservoir of subpatent Plasmodium falciparum infections within communities. This reservoir, often undetected, serves as a source of parasites and contributes to ongoing transmission and clinical malaria cases.

Persistent carriage of subpatent Plasmodium falciparum parasites associated with clinical malaria in a low transmission area in Senegal.

The merozoite surface antigen Pf41 was previously identified among the top 10 of new malaria vaccine candidates. Pf41 possesses red blood cell binding regions and conserved domains. We used population genetics approaches to determine the genetic diversity and to identify regions under balancing selection for the potential inclusion of Pf41 as candidate in a multicomponent vaccine. We screened 116 clinical isolates collected from different administrative regions in Senegal for P. falciparum positivity, Pf41 amplification and sequencing. We analyzed Pf41 sequences for polymorphism, natural selection, haplotype prevalence and linkage disequilibrium. Neutrality tests (Tajima's D, FLD, FLF and MEME) were computed using DnaSP v6. and Datamonkey Hyphy. Population Analysis with Reticulate Trees (Popart) version 1.7 software was used to construct haplotypes network showing the distribution of haplotypes per study site. P. falciparum positivity from the 116 successfully tested samples was 93.1% of which 73 were successfully sequenced for Pf41. We found a low genetic diversity (π = 0.00144 ± 0.00022) and high haplotype diversity (Hd = 0.765 ± 0.037) of Pf41 sequences that can be attributed to linkage disequilibrium. We identified several substitutions under positive selection and negatively selected codons at inter-species level in the central and 6-Cys domains of Pf41, respectively. The predominant SNP S232R was found fixed by positive selection in Senegalese isolates. The genetic diversity of Pf41 antigen is low in clinical isolates from Senegal. With a central domain under balancing selection and two highly conserved 6-Cys domains under negative selection due to functional constraints, the Pf41 antigen appears as a good vaccine candidate. Further monitoring of allelic variants on larger and diverse sets of samples would justify the rational for functional assays and Pf41 integration in a multicomponent vaccine.

Genetic diversity and natural selection of Plasmodium falciparum Pf41 vaccine candidate in clinical isolates from Senegal.

Serological assays are key tools in infectious disease surveillance, enabling detection of past infections by measuring antibody responses. Determining appropriate sero-positivity cut-offs, thresholds distinguishing between positive and negative antibody responses, remains a critical methodological challenge.

Article	Year
Evidence for multiple B- and T-cell epitopes in Plasmodium falciparum liver-stage antigen 3. Infection and immunity\| PubMed ID: 19139199	2009
Dramatic declines in seropositivity as determined with crude extracts of Plasmodium falciparum schizonts between 2000 and 2010 in Dielmo and Ndiop, Senegal. Malaria journal\| PubMed ID: 24602390	2014
The rise and fall of malaria in a West African rural community, Dielmo, Senegal, from 1990 to 2012: a 22 year longitudinal study. The Lancet. Infectious diseases\| PubMed ID: 24813159	2014
The implication of long-lasting insecticide-treated net use in the resurgence of malaria morbidity in a Senegal malaria endemic village in 2010-2011. Parasites & vectors\| PubMed ID: 25963402	2015
Unexpected high circulation of Plasmodium vivax in asymptomatic children from Kédougou, southeastern Senegal. Malaria journal\| PubMed ID: 29284488	2017
Dramatic Changes in Malaria Population Genetic Complexity in Dielmo and Ndiop, Senegal, Revealed Using Genomic Surveillance. The Journal of infectious diseases\| PubMed ID: 29325146	2018
Correction to: Fine-scale Spatiotemporal Mapping of Asymptomatic and Clinical Plasmodium falciparum Infections: Epidemiological Evidence for Targeted Malaria Elimination Interventions. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America\| PubMed ID: 35472079	2022
One hundred malaria attacks since birth. A longitudinal study of African children and young adults exposed to high malaria transmission. EClinicalMedicine\| PubMed ID: 38188691	2024
Persistent carriage of subpatent Plasmodium falciparum parasites associated with clinical malaria in a low transmission area in Senegal. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases\| PubMed ID: 39151787	2024
Genetic diversity and natural selection of Plasmodium falciparum Pf41 vaccine candidate in clinical isolates from Senegal. Scientific reports\| PubMed ID: 40360613	2025
Whose line is it anyway? Defining sero-positivity cut-offs for infectious disease surveillance. The Journal of infectious diseases\| PubMed ID: 41108092	2025

Aissatou Toure-Balde

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