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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 -
Oxford Open Immunology 2024Dengue virus (DENV) poses a global health threat, affecting millions individuals annually with no specific therapy and limited vaccines. Mosquitoes, mainly and...
Dengue virus (DENV) poses a global health threat, affecting millions individuals annually with no specific therapy and limited vaccines. Mosquitoes, mainly and worldwide, transmit DENV through their saliva during blood meals. In this study, we aimed to understand how mosquito saliva modulate skin immune responses during DENV infection in individuals living in mosquito-endemic regions. To accomplish this, we dissociated skin cells from Cambodian volunteers and incubated them with salivary gland extract (SGE) from three different mosquito strains: USDA strain, and wild type (WT) in the presence/absence of DENV. We observed notable alterations in skin immune cell phenotypes subsequent to exposure to salivary gland extract (SGE). Specifically, exposure lead to an increase in the frequency of macrophages expressing chemokine receptor CCR2, and neutrophils expressing CD69. Additionally, we noted a substantial increase in the percentage of macrophages that became infected with DENV in the presence of SGE. Differences in cellular responses were observed when SGE of three distinct mosquito strains were compared. Our findings deepen the understanding of mosquito saliva's role in DENV infection and skin immune responses in individuals regularly exposed to mosquito bites. This study provides insights into skin immune cell dynamics that could guide strategies to mitigate DENV transmission and other arbovirus diseases.
PubMed: 38737941
DOI: 10.1093/oxfimm/iqae003 -
Malaria Journal May 2024The newly developed malaria vaccine called "R21/Matrix-M malaria vaccine" showed a high safety and efficacy level, and Ghana is the first country to approve this new...
BACKGROUND
The newly developed malaria vaccine called "R21/Matrix-M malaria vaccine" showed a high safety and efficacy level, and Ghana is the first country to approve this new vaccine. The present study aimed to evaluate the rate of vaccine hesitancy (VH) towards the newly developed malaria vaccine among parents who currently have children who are not eligible for the vaccine but may be eligible in the near future. Additionally, the study aimed to identify the factors that could potentially influence VH.
METHODS
A cross-sectional survey using both online-based questionnaires and face-to-face interviews was conducted in Ghana from June to August 2023. The survey specifically targeted parents of ineligible children for vaccination, including those aged less than 5 months or between 3 and 12 years. The Parent Attitudes about Childhood Vaccination (PACV) scale was used to assess parental VH.
RESULTS
A total of 765 people participated in this study. Their median age was 36.0 years with an interquartile range of 31.0-41.0 years, 67.7% were females, 41.8% completed their tertiary education, 63.3% were married, 81.6% worked in non-healthcare sectors, and 59.7% reported that their monthly income was insufficient. About one-third (34.5%) of the parents were hesitant to give their children the R21/Matrix-M malaria vaccine. The following predictors were associated with VH: working in the healthcare sector (adjusted odds ratio (AOR) = 0.50; 95% confidence interval (CI) 0.30-0.80; p = 0.005), having the other parent working in the healthcare sector (AOR = 0.54; 95% CI 0.30-0.94; p = 0.034), and not taking scheduled routine vaccinations (AOR = 1.90; 95% CI 1.27-2.84; p = 0.002).
CONCLUSIONS
Addressing VH is crucial for optimizing R21/Matrix-M vaccine coverage in Ghana's malaria control strategy. By tackling VH issues, Ghana can effectively safeguard children's health in malaria-prone areas.
Topics: Humans; Ghana; Cross-Sectional Studies; Female; Male; Malaria Vaccines; Adult; Parents; Child, Preschool; Child; Vaccination Hesitancy; Infant; Surveys and Questionnaires; Vaccination; Malaria; Middle Aged
PubMed: 38734664
DOI: 10.1186/s12936-024-04921-2 -
The Lancet. Infectious Diseases May 2024The first licensed malaria vaccine, RTS,S/AS01, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a...
Genotypic analysis of RTS,S/AS01 malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5-17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial.
BACKGROUND
The first licensed malaria vaccine, RTS,S/AS01, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy.
METHODS
Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01 regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291.
FINDINGS
We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01 regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01 regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053).
INTERPRETATION
All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation.
FUNDING
GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.
PubMed: 38723650
DOI: 10.1016/S1473-3099(24)00179-8 -
Malaria Journal May 2024In 2021 and 2023, the World Health Organization approved RTS,S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African...
Genetic polymorphism and evidence of signatures of selection in the Plasmodium falciparum circumsporozoite protein gene in Tanzanian regions with different malaria endemicity.
BACKGROUND
In 2021 and 2023, the World Health Organization approved RTS,S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of Plasmodium falciparum circumsporozoite protein (PfCSP), but polymorphisms in the gene raise concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the Pfcsp genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission intensities in Mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country.
METHODS
The analysis involved 589 whole genome sequences generated by and as part of the MalariaGEN Community Project. The samples were collected between 2013 and January 2015 from five regions of Mainland Tanzania: Morogoro and Tanga (Muheza) (moderate transmission areas), and Kagera (Muleba), Lindi (Nachingwea), and Kigoma (Ujiji) (high transmission areas). Wright's inbreeding coefficient (F), Wright's fixation index (F), principal component analysis, nucleotide diversity, and Tajima's D were used to assess within-host parasite diversity, population structure and natural selection.
RESULTS
Based on F (< 0.95), there was high polyclonality (ranging from 69.23% in Nachingwea to 56.9% in Muheza). No population structure was detected in the Pfcsp gene in the five regions (mean F = 0.0068). The average nucleotide diversity (π), nucleotide differentiation (K) and haplotype diversity (Hd) in the five regions were 4.19, 0.973 and 0.0035, respectively. The C-terminal region of Pfcsp showed high nucleotide diversity at Th2R and Th3R regions. Positive values for the Tajima's D were observed in the Th2R and Th3R regions consistent with balancing selection. The Pfcsp C-terminal sequences revealed 50 different haplotypes (H_1 to H_50), with only 2% of sequences matching the 3D7 strain haplotype (H_50). Conversely, with the NF54 strain, the Pfcsp C-terminal sequences revealed 49 different haplotypes (H_1 to H_49), with only 0.4% of the sequences matching the NF54 strain (Hap_49).
CONCLUSIONS
The findings demonstrate high diversity of the Pfcsp gene with limited population differentiation. The Pfcsp gene showed positive Tajima's D values, consistent with balancing selection for variants within Th2R and Th3R regions. The study observed differences between the intended haplotypes incorporated into the design of RTS,S and R21 vaccines and those present in natural parasite populations. Therefore, additional research is warranted, incorporating other regions and more recent data to comprehensively assess trends in genetic diversity within this important gene. Such insights will inform the choice of alleles to be included in the future vaccines.
Topics: Humans; Endemic Diseases; Malaria, Falciparum; Plasmodium falciparum; Polymorphism, Genetic; Protozoan Proteins; Selection, Genetic; Tanzania
PubMed: 38720288
DOI: 10.1186/s12936-024-04974-3 -
Nature Communications May 2024The coronavirus disease 2019 (COVID-19) pandemic, along with the implementation of public health and social measures (PHSMs), have markedly reshaped infectious disease...
The coronavirus disease 2019 (COVID-19) pandemic, along with the implementation of public health and social measures (PHSMs), have markedly reshaped infectious disease transmission dynamics. We analysed the impact of PHSMs on 24 notifiable infectious diseases (NIDs) in the Chinese mainland, using time series models to forecast transmission trends without PHSMs or pandemic. Our findings revealed distinct seasonal patterns in NID incidence, with respiratory diseases showing the greatest response to PHSMs, while bloodborne and sexually transmitted diseases responded more moderately. 8 NIDs were identified as susceptible to PHSMs, including hand, foot, and mouth disease, dengue fever, rubella, scarlet fever, pertussis, mumps, malaria, and Japanese encephalitis. The termination of PHSMs did not cause NIDs resurgence immediately, except for pertussis, which experienced its highest peak in December 2023 since January 2008. Our findings highlight the varied impact of PHSMs on different NIDs and the importance of sustainable, long-term strategies, like vaccine development.
Topics: Humans; COVID-19; China; SARS-CoV-2; Communicable Diseases; Pandemics; Incidence; Seasons; Public Health; Communicable Disease Control
PubMed: 38719858
DOI: 10.1038/s41467-024-48201-8