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MedRxiv : the Preprint Server For... Jun 2024Understanding COVID-19's impact on children is vital for public health policy, yet age-specific data is scarce, especially in Uganda. This study examines SARS-CoV-2...
BACKGROUND
Understanding COVID-19's impact on children is vital for public health policy, yet age-specific data is scarce, especially in Uganda. This study examines SARS-CoV-2 seroprevalence and risk factors among Ugandan children at two timepoints, along with COVID-19-related knowledge and practices in households, including adult vaccination status.
METHODS
Baseline surveys were conducted in 12 communities from April to May 2021 (post-Alpha wave) and follow-up surveys in 32 communities from November 2021 to March 2022 (Omicron wave). Household questionnaires and blood samples were collected to test for malaria by microscopy and for SARS-CoV-2 using a Luminex assay. Seroprevalence was estimated at both the survey and community level. Mixed-effects logistic regression models assessed the association between individual and household factors and SARS-CoV-2 seropositivity in children, adjusting for household clustering.
RESULTS
More households reported disruptions in daily life at baseline compared to follow-up, though economic impacts lingered. By the follow-up survey, 52.7% of adults had received at least one COVID-19 vaccine dose. Overall seroprevalence in children was higher at follow-up compared to baseline (71.6% versus 19.2%, p < 0.001). Seroprevalence in children ranged across communities from 6-37% at baseline and 50-90% at follow-up. At baseline, children from the poorest households were more likely to be infected. Increasing age remained the only consistent risk factor for SARS-CoV-2 seroconversion at both timepoints.
CONCLUSIONS
Results indicate that a larger number of children were infected by the Delta and Omicron waves of COVID-19 compared to the Alpha wave. This study is the largest seroprevalence survey in children in Uganda, providing evidence that most children were infected with SARS-CoV-2 before the vaccine was widely available to pediatric populations. Pediatric infections were vastly underreported by case counts, highlighting the importance of seroprevalence surveys in assessing disease burden when testing and reporting rates are limited and many cases are mild or asymptomatic.
PubMed: 38947039
DOI: 10.1101/2024.06.09.24308673 -
PLoS Pathogens Jun 2024Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to...
Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.
PubMed: 38941356
DOI: 10.1371/journal.ppat.1012334 -
Journal of Immunology Research 2024Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19).... (Review)
Review
Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19). Considering the ongoing need for new COVID-19 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS-CoV-2 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T-cell epitopes critical for SARS-CoV-2 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID-19 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long-lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long-lasting, and it can persist up to 11 years post-infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID-19 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. This study discusses the use of nucleocapsid alone and its combination with spike protein or other proteins of SARS-CoV-2.
Topics: Humans; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Coronavirus Nucleocapsid Proteins; Immunogenicity, Vaccine; Animals; Phosphoproteins; Spike Glycoprotein, Coronavirus; Epitopes, T-Lymphocyte; Antibodies, Viral; Nucleocapsid Proteins
PubMed: 38939745
DOI: 10.1155/2024/9313267 -
Parasites & Vectors Jun 2024Indoor residual spraying (IRS) has been implemented to prevent malaria in Zambia for several decades, but its effectiveness has not been evaluated long term and in Vubwi...
BACKGROUND
Indoor residual spraying (IRS) has been implemented to prevent malaria in Zambia for several decades, but its effectiveness has not been evaluated long term and in Vubwi District yet. This study aimed to assess the association between IRS and the malaria burden in Zambia and Vubwi District and to explore the factors associated with refusing IRS.
METHODS
A retrospective study was used to analyze the association between IRS and malaria incidence in Zambia in 2001-2020 and in Vubwi District in 2014-2020 by Spearman correlation analysis. A case-control study was used to explore the factors associated with IRS refusals by households in Vubwi District in 2021. A logistic regression model was performed to identify factors associated with IRS refusals.
RESULTS
The malaria incidence reached its peak (391/1000) in 2001 and dropped to the lowest (154/1000) in 2019. The annual percentage change in 2001-2003, 2003-2008, 2008-2014, 2014-2018 and 2018-2020 was - 6.54%, - 13.24%, 5.04%, - 10.28% and 18.61%, respectively. A significantly negative correlation between the percentage of population protected by the IRS against the total population in Zambia (coverage) and the average malaria incidence in the whole population was observed in 2005-2020 (r = - 0.685, P = 0.003) and 2005-2019 (r = - 0.818, P < 0.001). Among 264 participants (59 in the refuser group and 205 in the acceptor group), participants with specific occupations (self-employed: OR 0.089, 95% CI 0.022-0.364; gold panning: OR 0.113, 95% CI 0.022-0.574; housewives: OR 0.129, 95% CI 0.026-0.628 and farmers: OR 0.135, 95% CI 0.030-0.608 compared to employees) and no malaria case among household members (OR 0.167; 95% CI 0.071-0.394) had a lower risk of refusing IRS implementation, while those with a secondary education level (OR 3.690, 95% CI 1.245-10.989) had a higher risk of refusing IRS implementation compared to those who had never been to school.
CONCLUSIONS
Increasing coverage with IRS was associated with decreasing incidence of malaria in Zambia, though this was not observed in Vubwi District, possibly because of the special geographical location of Vubwi District. Interpersonal communication and targeted health education should be implemented at full scale to ensure household awareness and gain community trust.
Topics: Zambia; Humans; Case-Control Studies; Malaria; Mosquito Control; Incidence; Retrospective Studies; Insecticides; Female; Male; Animals; Adult; Child, Preschool; Child; Adolescent
PubMed: 38937791
DOI: 10.1186/s13071-024-06328-z -
Infection, Genetics and Evolution :... Jun 2024In malaria parasites, the erythrocyte binding-like proteins (EBL) are a family of invasion proteins that are attractive vaccine targets. In the case of Plasmodium vivax,...
In malaria parasites, the erythrocyte binding-like proteins (EBL) are a family of invasion proteins that are attractive vaccine targets. In the case of Plasmodium vivax, the widespread malaria parasite, blood-stage vaccines have been largely focused on a single EBL candidate, the Duffy binding-like domain (DBL) of the Duffy binding protein (DBPII), due to its well-characterized role in the reticulocyte invasion. A novel P. vivax EBL family member, the Erythrocyte binding protein (EBP2, also named EBP or DBP2), binds preferentially to reticulocytes and may mediate an alternative P. vivax invasion pathway. To gain insight into the natural genetic diversity of the DBL domain of EBP2 (region II; EBP2-II), we analyzed ebp2-II gene sequences of 71 P. vivax isolates collected in different endemic settings of the Brazilian Amazon rainforest, where P. vivax is the predominant malaria-associated species. Although most of the substitutions in the ebp2-II gene were non-synonymous and suggested positive selection, the results showed that the DBL domain of the EBP2 was much less polymorphic than that of DBPII. The predominant EBP2 haplotype in the Amazon region corresponded to the C127 reference sequence first described in Cambodia (25% C127-like haplotype). An overview of ebp2-II gene sequences available at GenBank (n = 352) from seven countries (Cambodia, Madagascar, Myanmar, PNG, South Korea, Thailand, Vietnam) confirmed the C127-like haplotype as highly prevalent worldwide. Two out of 43 haplotypes (5 to 20 inferred per country) showed a global frequency of 60%. The results presented here open new avenues of research pursuit while suggesting that a vaccine based on the DBL domain of EBP2 should target a few haplotypes for broad coverage.
PubMed: 38936525
DOI: 10.1016/j.meegid.2024.105628 -
PLoS Pathogens Jun 2024
Review
Topics: Malaria Vaccines; Humans; Vaccine Development; Malaria; Animals; Plasmodium falciparum; Malaria, Falciparum
PubMed: 38935630
DOI: 10.1371/journal.ppat.1012309 -
Antibody Therapeutics Apr 2024The recent discovery of public antibodies targeting -encoded repetitive interspersed families of polypeptides (RIFINs), which contain extracellular immunoglobulin-like... (Review)
Review
The recent discovery of public antibodies targeting -encoded repetitive interspersed families of polypeptides (RIFINs), which contain extracellular immunoglobulin-like domains from LAIR1 or LILRB1, constitutes a significant step forward in comprehending the reactivity of the parasite. These antibodies arise from unique B cell clones and demonstrate extensive cross-reactivity through their interaction with RIFINs. LAIR1 and LILRBs are specialized type I transmembrane glycoproteins, classified as immune inhibitory receptors, restricted to primates and mainly found on hematopoietic cells. They are instrumental in modulating interactions within the tumor microenvironment and across the immune system, and are increasingly recognized as important in anti-cancer immunotherapy and pathogen defense. The presence of LAIR1/LILRB1-containing antibodies offers new insights into malaria parasite evasion strategies and the immune system's response. Additionally, the innovative method of integrating extra exons into the antibody switch region is a noteworthy advancement, enriching the strategies for the generation of a varied array of bispecific and multispecific antibodies.
PubMed: 38933531
DOI: 10.1093/abt/tbae008 -
Vaccines May 2024While two circumsporozoite protein-based pre-erythrocytic vaccines (PEV), RTS,S and R21, have been approved by the WHO, no blood-stage vaccine (BSV) or... (Review)
Review
While two circumsporozoite protein-based pre-erythrocytic vaccines (PEV), RTS,S and R21, have been approved by the WHO, no blood-stage vaccine (BSV) or transmission-blocking vaccine (TBV) has reached a phase 3 trial. One of the major obstacles that slows down malaria vaccine development is the shortage (or lack) of in vitro assays or animal models by which investigators can reasonably select the best vaccine formulation (e.g., antigen, adjuvant, or platform) and/or immunization strategy (e.g., interval of inoculation or route of immunization) before a human phase 2 trial. In the case of PEV, RTS,S and R21 have set a benchmark, and a new vaccine can be compared with (one of) the approved PEV directly in preclinical or early clinical studies. However, such an approach cannot be utilized for BSV or TBV development at this moment. The focus of this review is in vitro assays or in vivo models that can be used for BSV or TBV development, and I discuss important considerations during assay selection, standardization, qualification, validation, and interpretation of the assay results. Establishment of a robust assay/model with proper interpretation of the results is the one of key elements to accelerate future vaccine development.
PubMed: 38932315
DOI: 10.3390/vaccines12060586 -
International Journal of Molecular... Jun 2024Mutations have driven the evolution and development of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with potential implications for...
Mutations have driven the evolution and development of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with potential implications for increased transmissibility, disease severity and vaccine escape among others. Genome sequencing is a technique that allows scientists to read the genetic code of an organism and has become a powerful tool for studying emerging infectious diseases. Here, we conducted a cross-sectional study in selected districts of the Eastern Province of Zambia, from November 2021 to February 2022. We analyzed SARS-CoV-2 samples ( = 76) using high-throughput sequencing. A total of 4097 mutations were identified in 69 SARS-CoV-2 genomes with 47% (1925/4097) of the mutations occurring in the spike protein. We identified 83 unique amino acid mutations in the spike protein of the seven Omicron sublineages (BA.1, BA.1.1, BA.1.14, BA.1.18, BA.1.21, BA.2, BA.2.23 and XT). Of these, 43.4% (36/83) were present in the receptor binding domain, while 14.5% (12/83) were in the receptor binding motif. While we identified a potential recombinant XT strain, the highly transmissible BA.2 sublineage was more predominant (40.8%). We observed the substitution of other variants with the Omicron strain in the Eastern Province. This work shows the importance of pandemic preparedness and the need to monitor disease in the general population.
Topics: Zambia; Humans; SARS-CoV-2; COVID-19; Genome, Viral; Spike Glycoprotein, Coronavirus; Mutation; Cross-Sectional Studies; Retrospective Studies; Phylogeny; Genomics; High-Throughput Nucleotide Sequencing
PubMed: 38928045
DOI: 10.3390/ijms25126338 -
International Immunopharmacology Jun 2024
PubMed: 38926073
DOI: 10.1016/j.intimp.2024.112260