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Malaria Journal May 2024Plasmodium falciparum malaria is a public health issue mostly seen in tropical countries. Until now, there is no effective malaria vaccine against antigens specific to...
BACKGROUND
Plasmodium falciparum malaria is a public health issue mostly seen in tropical countries. Until now, there is no effective malaria vaccine against antigens specific to the blood-stage of P. falciparum infection. Because the pathogenesis of malarial disease results from blood-stage infection, it is essential to identify the most promising blood-stage vaccine candidate antigens under natural exposure to malaria infection.
METHODS
A cohort of 400 pregnant women and their infants was implemented in South Benin. An active and passive protocol of malaria surveillance was established during pregnancy and infancy to precisely ascertain malaria infections during the follow-up. Twenty-eight antibody (Ab) responses specific to seven malaria candidate vaccine antigens were repeatedly quantified during pregnancy (3 time points) and infancy (6 time points) in order to study the Ab kinetics and their protective role. Abs were quantified by ELISA and logistic, linear and cox-proportional hazard model were performed to analyse the associations between Ab responses and protection against malaria in mothers and infants, taking into account socio-economic factors and for infants an environmental risk of exposure.
RESULTS
The levels of IgM against MSP1, MSP2 and MSP3 showed an early protective response against the onset of symptomatic malaria infections starting from the 18th month of life, whereas no association was found for IgG responses during infancy. In women, some IgG responses tend to be associated with a protection against malaria risk along pregnancy and at delivery, among them IgG3 against GLURP-R0 and IgG2 against MSP1.
CONCLUSION
The main finding suggests that IgM should be considered in vaccine designs during infanthood. Investigation of the functional role played by IgM in malaria protection needs further attention.
Topics: Humans; Female; Plasmodium falciparum; Malaria, Falciparum; Pregnancy; Infant; Immunoglobulin M; Immunoglobulin G; Antibodies, Protozoan; Benin; Antigens, Protozoan; Adult; Young Adult; Enzyme-Linked Immunosorbent Assay; Infant, Newborn; Pregnancy Complications, Parasitic; Cohort Studies
PubMed: 38764069
DOI: 10.1186/s12936-024-04970-7 -
Infection, Genetics and Evolution :... Aug 2024Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) is a promising candidate target for the development of multi-component vaccines. Therefore, determining the genetic...
Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) is a promising candidate target for the development of multi-component vaccines. Therefore, determining the genetic variation pattern of Pvmsp8 is essential in providing a reference for the rational design of the P. vivax malaria vaccines. This study delves into the genetic characteristics of the Pvmsp8 gene, specifically focusing on samples from the China-Myanmar border (CMB) region, and contrasts these findings with broader global patterns. The study uncovers that Pvmsp8 exhibits a notable level of conservation across different populations, with limited polymorphisms and relatively low nucleotide diversity (0.00023-0.00120). This conservation contrasts starkly with the high polymorphisms found in other P. vivax antigens such as Pvmsp1. A total of 25 haplotypes and 14 amino acid mutation sites were identified in the global populations, and all mutation sites were confined to non-functional regions. The study also notes that most CMB Pvmsp8 haplotypes are shared among Burmese, Cambodian, Thai, and Vietnamese populations, indicating less geographical variance, but differ notably from those found in Pacific island regions or the Panama. The findings underscore the importance of considering regional genetic diversity in P. vivax when developing targeted malaria vaccines. Non departure from neutral evolution were found by Tajima's D test, however, statistically significant differences were observed between the kn/ks rates. The study's findings are crucial in understanding the evolution and population structure of the Pvmsp8 gene, particularly during regional malaria elimination efforts. The highly conserved nature of Pvmsp8, combined with the lack of mutations in its functional domain, presents it as a promising candidate for developing a broad and effective P. vivax vaccine. This research thus lays a foundation for the rational development of multivalent malaria vaccines targeting this genetically stable antigen.
Topics: Plasmodium vivax; Selection, Genetic; Protozoan Proteins; Haplotypes; Humans; Genetic Variation; Malaria, Vivax; Mutation; Phylogeny; Antigens, Protozoan
PubMed: 38759940
DOI: 10.1016/j.meegid.2024.105605 -
Wellcome Open Research 2023Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures...
BACKGROUND
Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures have been substantially scaled up, such as insecticide-treated bed nets, artemisinin-based combination therapies, and, more recently, the introduction of the malaria vaccine, the RTS,S/AS01. In this paper, we describe the epidemiology of malaria for the last two decades to understand the past transmission and set the scene for the elimination agenda.
METHODS
A collation of parasite prevalence surveys conducted between the years 2000 and 2022 was done. A spatio-temporal geostatistical model was fitted to predict the yearly malaria risk for children aged 2-10 years (PfPR 2-10) at 1×1 km spatial resolutions. Parameter estimation was done using the Monte Carlo maximum likelihood method. District-level prevalence estimates adjusted for population are calculated for the years 2000 to 2022.
RESULTS
A total of 2,595 sampled unique locations from 2000 to 2022 were identified through the data collation exercise. This represents 70,565 individuals that were sampled in the period. In general, the PfPR2_10 declined over the 22 years. The mean modelled national PfPR2_10 in 2000 was 43.93 % (95% CI:17.9 to 73.8%) and declined to 19.2% (95%CI 7.49 to 37.0%) in 2022. The smoothened estimates of PfPR2_10 indicate that malaria prevalence is very heterogeneous with hotspot areas concentrated on the southern shores of Lake Malawi and the country's central region.
CONCLUSIONS
The last two decades are associated with a decline in malaria prevalence, highly likely associated with the scale-up of control interventions. The country should move towards targeted malaria control approaches informed by surveillance data.
PubMed: 38756913
DOI: 10.12688/wellcomeopenres.19390.2 -
Malaria Journal May 2024Sporozoite invasion of hepatocytes is an essential step in the Plasmodium life-cycle and has similarities, at the cellular level, to merozoite invasion of erythrocytes....
BACKGROUND
Sporozoite invasion of hepatocytes is an essential step in the Plasmodium life-cycle and has similarities, at the cellular level, to merozoite invasion of erythrocytes. In the case of the Plasmodium blood-stage, efforts to identify host-pathogen protein-protein interactions have yielded important insights including vaccine candidates. In the case of sporozoite-hepatocyte invasion, the host-pathogen protein-protein interactions involved are poorly understood.
METHODS
To gain a better understanding of the protein-protein interaction between the sporozoite ligands and host receptors, a systematic screen was performed. The previous Plasmodium falciparum and human surface protein ectodomain libraries were substantially extended, resulting in the creation of new libraries comprising 88 P. falciparum sporozoite protein coding sequences and 182 sequences encoding human hepatocyte surface proteins. Having expressed recombinant proteins from these sequences, a plate-based assay was used, capable of detecting low affinity interactions between recombinant proteins, modified for enhanced throughput, to screen the proteins for interactions. The novel interactions identified in the screen were characterized biochemically, and their essential role in parasite invasion was further elucidated using antibodies and genetically manipulated Plasmodium parasites.
RESULTS
A total of 7540 sporozoite-hepatocyte protein pairs were tested under conditions capable of detecting interactions of at least 1.2 µM K. An interaction between the human fibroblast growth factor receptor 4 (FGFR4) and the P. falciparum protein Pf34 is identified and reported here, characterizing its affinity and demonstrating the blockade of the interaction by reagents, including a monoclonal antibody. Furthermore, further interactions between Pf34 and a second P. falciparum rhoptry neck protein, PfRON6, and between human low-density lipoprotein receptor (LDLR) and the P. falciparum protein PIESP15 are identified. Conditional genetic deletion confirmed the essentiality of PfRON6 in the blood-stage, consistent with the important role of this protein in parasite lifecycle. Pf34 was refractory to attempted genetic modification. Antibodies to Pf34 abrogated the interaction and had a modest effect upon sporozoite invasion into primary human hepatocytes.
CONCLUSION
Pf34 and PfRON6 may be members of a functionally important invasion complex which could be a target for future interventions. The modified interaction screening assay, protein expression libraries and P. falciparum mutant parasites reported here may be a useful tool for protein interaction discovery and antigen candidate screening which could be of wider value to the scientific community.
Topics: Plasmodium falciparum; Hepatocytes; Humans; Sporozoites; Protozoan Proteins; Host-Pathogen Interactions; Membrane Proteins; Receptors, Cell Surface; Host-Parasite Interactions; Protein Binding
PubMed: 38755636
DOI: 10.1186/s12936-024-04913-2 -
Clinical and Experimental Vaccine... Apr 2024The global burden of disease and mortality is greatly influenced by malaria, particularly in children. Nigeria alone accounts for about 25% of global malaria cases and...
PURPOSE
The global burden of disease and mortality is greatly influenced by malaria, particularly in children. Nigeria alone accounts for about 25% of global malaria cases and fatalities. Despite efforts to control and eliminate malaria, conventional treatments have limitations, prompting the need for a vaccine. However, while efforts have focused on researching and developing malaria vaccines, less attention has been given to public acceptance and preparedness for vaccination.
MATERIALS AND METHODS
The study employed a cross-sectional approach to assess the knowledge, perceptions, and readiness of caregivers towards the malaria vaccine. Data were collected through a physical and online survey among a representative sample of caregivers across the six geopolitical regions of Nigeria. The data was analyzed using principal component analysis and percentages.
RESULTS
Out of 347 respondents, 180 (51%) men, 165 (46.6%) women, 2 (0.5%) transgender, 156 (45%) rural settlers, and 191 (55%) urban settlers were identified in this study. The study reported an overall acceptance rate of 78.4% and 21.6% resistance rate. The age group between 21-30 years recorded the highest 207 (59.6%). A significant number of participants, 252 (59.6%), held at least a higher or post-secondary certificate, out of which 193 (55.6%) demonstrated strong readiness to accept the malaria vaccine. The study showed that fear of adverse effects was the main reason for malaria vaccine resistance among caregivers.
CONCLUSION
This study's findings offer valuable insights into caregivers' knowledge about the malaria vaccine, highlighting the factors that impact the acceptance of the malaria vaccine.
PubMed: 38752001
DOI: 10.7774/cevr.2024.13.2.121 -
Frontiers in Immunology 2024are the most prolific mosquito vectors in the world. Found on every continent, they can effectively transmit various arboviruses, including the dengue virus which...
INTRODUCTION
are the most prolific mosquito vectors in the world. Found on every continent, they can effectively transmit various arboviruses, including the dengue virus which continues to cause outbreaks worldwide and is spreading into previously non-endemic areas. The lack of widely available dengue vaccines accentuates the importance of targeted vector control strategies to reduce the dengue burden. High-throughput tools to estimate human-mosquito contact and evaluate vector control interventions are lacking. We propose a novel serological tool that allows rapid screening of human cohorts for exposure to potentially infectious mosquitoes.
METHODS
We tested 563 serum samples from a longitudinal pediatric cohort study previously conducted in Cambodia. Children enrolled in the study were dengue-naive at baseline and were followed biannually for dengue incidence for two years. We used Western blotting and enzyme-linked immunosorbent assays to identify immunogenic salivary proteins and measure total anti- IgG.
RESULTS
We found a correlation (rs=0.86) between IgG responses against AeD7L1 and AeD7L2 recombinant proteins and those to whole salivary gland homogenate. We observed seasonal fluctuations of AeD7L1+2 IgG responses and no cross-reactivity with and mosquitoes. The baseline median AeD7L1+2 IgG responses for young children were higher in those who developed asymptomatic versus symptomatic dengue.
DISCUSSION
The IgG response against AeD7L1+2 recombinant proteins is a highly sensitive and specific marker of human exposure to bites that can facilitate standardization of future serosurveys and epidemiological studies by its ability to provide a robust estimation of human-mosquito contact in a high-throughput fashion.
Topics: Humans; Aedes; Animals; Salivary Proteins and Peptides; Child; Mosquito Vectors; Dengue; Insect Proteins; Female; Child, Preschool; Immunoglobulin G; Male; Cambodia; Longitudinal Studies; Dengue Virus; Adolescent; Insect Bites and Stings
PubMed: 38751433
DOI: 10.3389/fimmu.2024.1368066 -
BioRxiv : the Preprint Server For... May 2024Genomic surveillance is crucial for identifying at-risk populations for targeted malaria control and elimination. Identity-by-descent (IBD) is being used in population...
Genomic surveillance is crucial for identifying at-risk populations for targeted malaria control and elimination. Identity-by-descent (IBD) is being used in population genomics to estimate genetic relatedness, effective population size , population structure, and positive selection. However, a comprehensive evaluation of IBD segment detection tools is lacking for species with high rates of recombination. Here, we employ genetic simulations reflecting 's high recombination rate and decreasing to benchmark IBD callers, including probabilistic (hmmIBD, isoRelate), identity-by-state-based (hap-IBD, phased IBD) and others (Refined IBD), using genealogy-based true IBD and downstream inference of population characteristics. Our findings reveal that low marker density per genetic unit, related to high recombination rates relative to mutation rates, significantly affects the quality of detected IBD segments. Most IBD callers suffer from high false negative rates, which can be improved with parameter optimization. Optimized parameters allow for more accurate capture of selection signals and population structure, but hmmIBD is unique in providing less biased estimates of . Empirical data subsampled from the MalariaGEN 7 database, representing different transmission settings, confirmed these patterns. We conclude that the detection of IBD in high-recombining species requires context-specific evaluation and parameter optimization and recommend that hmmIBD be used for quality-sensitive analysis, such as estimation of in these species.
PubMed: 38746392
DOI: 10.1101/2024.05.04.592538 -
BioRxiv : the Preprint Server For... Apr 2024Reducing malaria transmission has been a major pillar of control programmes and is considered crucial for achieving malaria elimination. Gametocytes, the transmissible...
Reducing malaria transmission has been a major pillar of control programmes and is considered crucial for achieving malaria elimination. Gametocytes, the transmissible forms of the parasite, arise during the blood stage of the parasite and develop through 5 morphologically distinct stages. Immature gametocytes (stage I-IV) sequester and develop in the extravascular niche of the bone marrow and possibly spleen. Only mature stage V gametocytes re-enter peripheral circulation to be taken up by mosquitoes for successful onward transmission. We have recently shown that immature, but not mature gametocytes are targets of host immune responses and identified putative target surface antigens. We hypothesize that these antigens play a role in gametocyte sequestration and contribute to acquired transmission-reducing immunity. Here we demonstrate that surface antigen expression, serum reactivity by human IgG, and opsonic phagocytosis by macrophages all show similar dynamics during gametocyte maturation, i.e., on in immature and off in mature gametocytes. Moreover, the switch in surface reactivity coincides with reversal in phosphatidylserine (PS) surface exposure, a marker for red blood cell age and clearance. PS is exposed on the surface of immature gametocytes (as well as in late asexual stages) but is removed from the surface in later gametocyte stages (IV-V). Using parasite reverse genetics and drug perturbations, we confirm that parasite protein export into the host cell and phospholipid scramblase activity are required for the observed surface modifications in asexual and sexual stages. These findings suggest that the dynamic surface remodelling allows (i) immature gametocyte sequestration in bone marrow and (ii) mature gametocyte release into peripheral circulation and immune evasion, therefore contributing to mature gametocyte survival and onward transmission to mosquitoes. Importantly, blocking scramblase activity during gametocyte maturation results in efficient clearance of mature gametocytes, revealing a potential path for transmission blocking interventions. Our studies have important implications for our understanding of parasite biology and form a starting point for novel intervention strategies to simultaneously reduce parasite burden and transmission.
PubMed: 38746342
DOI: 10.1101/2024.04.30.591837 -
Frontiers in Immunology 2024Among spp. responsible for human malaria, ranks as the second most prevalent and has the widest geographical range; however, vaccine development has lagged behind that...
Among spp. responsible for human malaria, ranks as the second most prevalent and has the widest geographical range; however, vaccine development has lagged behind that of , the deadliest species. Recently, we developed a multistage vaccine for based on a heterologous prime-boost immunization regimen utilizing the attenuated vaccinia virus strain LC16m8Δ (m8Δ)-prime and adeno-associated virus type 1 (AAV1)-boost, and demonstrated 100% protection and more than 95% transmission-blocking (TB) activity in the mouse model. In this study, we report the feasibility and versatility of this vaccine platform as a multistage vaccine, which can provide 100% sterile protection against sporozoite challenge and >95% TB efficacy in the mouse model. Our vaccine comprises m8Δ and AAV1 viral vectors, both harboring the gene encoding two circumsporozoite (PvCSP) protein alleles (VK210; PvCSP-Sal and VK247; -PNG) and P25 (Pvs25) expressed as a Pvs25-PvCSP fusion protein. For protective efficacy, the heterologous m8Δ-prime/AAV1-boost immunization regimen showed 100% (short-term; Day 28) and 60% (long-term; Day 242) protection against PvCSP VK210 transgenic sporozoites. For TB efficacy, mouse sera immunized with the vaccine formulation showed >75% TB activity and >95% transmission reduction activity by a direct membrane feeding assay using isolates in blood from an infected patient from the Brazilian Amazon region. These findings provide proof-of-concept that the m8Δ/AAV1 vaccine platform is sufficiently versatile for vaccine development. Future studies are needed to evaluate the safety, immunogenicity, vaccine efficacy, and synergistic effects on protection and transmission blockade in a non-human primate model for Phase I trials.
Topics: Animals; Malaria Vaccines; Plasmodium vivax; Malaria, Vivax; Mice; Genetic Vectors; Dependovirus; Female; Protozoan Proteins; Antibodies, Protozoan; Disease Models, Animal; Vaccinia virus; Humans; Mice, Inbred BALB C; Immunization, Secondary; Vaccine Efficacy
PubMed: 38745665
DOI: 10.3389/fimmu.2024.1372584 -
Tropical Diseases, Travel Medicine and... May 2024In Ethiopia, malaria is one of the major public health and socioeconomic problems, though tremendous efforts have been made. Currently, the country has a plan to...
INTRODUCTION
In Ethiopia, malaria is one of the major public health and socioeconomic problems, though tremendous efforts have been made. Currently, the country has a plan to eliminate malaria by 2030. To achieve this plan, epidemiological studies associated with malaria prevalence with gender, age groups, species types, and seasons are essential. Therefore, the aim of this study was to assess the prevalence of malaria from 2013 to 2021 in Addis Zemen town, Northwest Ethiopia.
METHODS
A retrospective study was conducted at assess the trend of malaria prevalence over the last nine years using recorded blood smear reports in the laboratory logbook from governmental health institutions. Trends in malaria cases and the proportion of genders, age groups, species, and seasons over time were compared. The data were analyzed using the SPSS-23 software package.
RESULTS
The overall malaria prevalence between 2013 and 2021 was 10.4%. From all confirmed cases, the minimum and maximum prevalence of malaria cases were recorded in 2018 (2%) and 2016 (33.2%) years, respectively. The infectious rate of males (59.3%) was significantly higher than that of females (40.7%) (p < 0.0001). In all survey periods, all age groups were infected by malaria parasites; the majority of the cases were between 15 and 45 years (57%) older than others. Statistically, a greater proportion of P. falciparum (80.1%) was recorded than P. vivax (18.5%) (p < 0.0001). Malaria cases were occurring throughout each month. The relative highest peaks of total malaria cases were observed during the months of September, October, and November. Seasonally, the highest infection rate was observed during spring (40.20%) compared to other seasons.
CONCLUSIONS
In conclusion, the study revealed that malaria transmission remained high, which affected males more than females and potentially reproductive ages. Two of the most important Plasmodium species were identified and found during all reviewed months and years, though P. falciparum was the most prevalent. Hence, the problem can be alleviated by using season-based long-lasting insecticide treated nets, regularly overseeing ongoing irrigation activity, overseeing the reduction of the water level of the Sheni River, health education, and providing immediate patient treatment.
PubMed: 38745210
DOI: 10.1186/s40794-024-00219-y