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International Immunopharmacology Jun 2024
PubMed: 38926073
DOI: 10.1016/j.intimp.2024.112260 -
Pathogens (Basel, Switzerland) Jun 2024Enteric infections due to viral pathogens are a major public health concern. Detecting the risk areas requires a strong surveillance system for pathogenic viruses in...
Enteric infections due to viral pathogens are a major public health concern. Detecting the risk areas requires a strong surveillance system for pathogenic viruses in sources such as wastewater. Towards building an environmental surveillance system in Zambia, we aimed to identify group A rotavirus (RVA) and human adenovirus (HAdV) in wastewater. Convenient sampling was conducted at four study sites every Tuesday for five consecutive weeks. The research team focused on three different methods of viral concentration to determine the suitability in terms of cost and applicability for a regular surveillance system: the bag-mediated filtration system (BMFS), polyethylene glycol-based (PEG) precipitation, and skimmed milk (SM) flocculation. We screened 20 wastewater samples for HAdV and RVA using quantitative polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR). Of the 20 samples tested using qPCR, 18/20 (90%) tested positive for HAdV and 14/20 (70%) tested positive for RVA. For the genetic sequencing, qPCR positives were subjected to cPCR, of which 12 positives were successfully amplified. The human adenovirus was identified with a nucleotide identity range of 98.48% to 99.53% compared with the reference genome from GenBank. The BMFS and SM flocculation were the most consistent viral concentration methods for HAdV and RVA, respectively. A statistical analysis of the positives showed that viral positivity differed by site ( < 0.001). SM and PEG may be the most appropriate options in resource-limited settings such as Zambia due to the lower costs associated with these concentration methods. The demonstration of HAdV and RVA detection in wastewater suggests the presence of the pathogens in the communities under study and the need to establish a routine wastewater surveillance system for the identification of pathogens.
PubMed: 38921784
DOI: 10.3390/pathogens13060486 -
Drug Safety Jun 2024Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude... (Review)
Review
INTRODUCTION
Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs.
METHODS
We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources.
RESULTS
We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries.
CONCLUSION
The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring.
PubMed: 38907172
DOI: 10.1007/s40264-024-01445-1 -
Comparative Medicine Jun 2024Malaria is a parasitic disease caused by protozoan species of the genus and transmitted by female mosquitos of the genus and other Culicidae. Most of the parasites of...
Malaria is a parasitic disease caused by protozoan species of the genus and transmitted by female mosquitos of the genus and other Culicidae. Most of the parasites of the genus are highly species specific with more than 200 species described affecting different species of mammals, birds, and reptiles. species strictly affecting humans are , , , and More recently, and other nonhuman primate plasmodia were found to naturally infect humans. Currently, malaria occurs mostly in poor tropical and subtropical areas of the world, and in many of these countries it is the leading cause of illness and death. For more than 100 y, animal models, have played a major role in our understanding of malaria biology. Avian species were the first to be used as models to study human malaria. Malaria parasite biology and immunity were first studied using mainly and . Rodent malarias, particularly and , have been used extensively as models to study malaria in mammals. Several species of from nonhuman primates have been used as surrogate models to study human malaria immunology, pathogenesis, candidate vaccines, and treatments. , , and are important models for studying malaria produced by and , while is used as a model for studying severe malaria. Other nonhuman primate malarias used in research are , , , , and . Very few nonhuman primate species can develop an infection with human malarias. Macaques in general are resistant to infection with , , , and . Only apes and a few species of New World monkeys can support infection with human malarias. Herein we review the most common, and some less common, avian, reptile, and mammal plasmodia species used as models to study human malaria.
PubMed: 38902006
DOI: 10.30802/AALAS-CM-24-000019 -
Antiviral Research Jun 2024Most COVID-19 vaccines contain the SARS-CoV-2 spike protein as an antigen, but they lose efficacy as neutralizing antibody titers wane and escape variants emerge....
Most COVID-19 vaccines contain the SARS-CoV-2 spike protein as an antigen, but they lose efficacy as neutralizing antibody titers wane and escape variants emerge. Modifying the spike antigen to increase neutralizing antibody titers would help counteract this decrease in titer. We previously used a structure-based computational design method to identify nine amino acid changes in the receptor-binding domain (RBD) of spike that stabilize the RBD and increase the neutralizing antibody titers elicited by vaccination. Here, we introduce those enhancing amino acid changes into a full-length spike (FL-S-2P) ectodomain representative of most approved vaccine antigens. These amino acid changes can be incorporated into the FL-S-2P protein without negatively effecting expression or stability. Furthermore, the amino acid changes improved functional antibody titers in both mice and monkeys following vaccination. These amino acid changes could increase the duration of protection conferred by most COVID-19 vaccines.
PubMed: 38901738
DOI: 10.1016/j.antiviral.2024.105937 -
Cureus May 2024Malaria remains a significant global health challenge, with Plasmodium parasites transmitted by Anopheles mosquitoes causing substantial morbidity and mortality. Despite... (Review)
Review
Malaria remains a significant global health challenge, with Plasmodium parasites transmitted by Anopheles mosquitoes causing substantial morbidity and mortality. Despite historical efforts, malaria continues to affect millions worldwide, particularly in tropical regions. This systematic review aimed to assess the acceptability of the RTS, S/AS01 malaria vaccine among diverse populations. A comprehensive search strategy was employed across databases such as Cochrane Library, Embase, Google Scholar, and Medline. Studies were included based on specific criteria, including observational and cross-sectional designs involving adults. Data extraction and analysis were conducted meticulously, encompassing key variables related to vaccine acceptance rates and influencing factors. Analysis of 18 studies involving 18,561 participants revealed an overall malaria vaccine acceptance rate of 87.51%, ranging from 32.26% to 99.30%. Significant variations were observed based on demographics, with Ghana and Nigeria reporting high acceptance rates. Factors influencing acceptance included knowledge levels, past vaccination experiences, community preferences, and engagement in malaria prevention behaviors. Concerns about adverse reactions and regional disparities were noted as potential barriers to acceptance. This review highlights the importance of understanding public perceptions and concerns regarding malaria vaccines to enhance vaccine coverage and uptake. Tailored communication strategies, advocacy efforts, and targeted education interventions are crucial for addressing misconceptions and increasing vaccine acceptance. Policy recommendations should consider demographic and regional factors to ensure effective implementation of malaria vaccination programs, ultimately contributing to global malaria prevention efforts and public health initiatives.
PubMed: 38899238
DOI: 10.7759/cureus.60678 -
BioRxiv : the Preprint Server For... Jun 2024Rodent malaria models serve as important preclinical antimalarial and vaccine testing tools. Evaluating treatment outcomes in these models often requires manually...
Rodent malaria models serve as important preclinical antimalarial and vaccine testing tools. Evaluating treatment outcomes in these models often requires manually counting parasite-infected red blood cells (iRBCs), a time-consuming process, which can be inconsistent between individuals and labs. We have developed an easy-to-use machine learning (ML)-based software, Malaria Screener R, to expedite and standardize such studies by automating the counting of iRBCs in rodents. This software can process Giemsa-stained blood smear images captured by any camera-equipped microscope. It features an intuitive graphical user interface that facilitates image processing and visualization of the results. The software has been developed as a desktop application that processes images on standard Windows and Mac OS computers. A previous ML model created by the authors designed to count -infected human RBCs did not perform well counting -infected mouse RBCs. We leveraged that model by loading the pre-trained weights and training the algorithm with newly collected data to target and mouse iRBCs. This new model reliably measured both and parasitemia (R = 0.9916). Additional rounds of training data to incorporate variances due to length of Giemsa staining, microscopes etc, have produced a generalizable model, meeting WHO Competency Level 1 for the sub-category of parasite counting using independent microscopes. Reliable, automated analyses of blood-stage parasitemia will facilitate rapid and consistent evaluation of novel vaccines and antimalarials across labs in an easily accessible malaria model.
PubMed: 38895284
DOI: 10.1101/2024.06.05.597554 -
Nature Communications Jun 2024Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the...
Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody development following repeat CHMI. After two exposures, time to blood stage patency increases significantly and the number of reported symptoms decreases indicating the development of clinical tolerance. The time to patency correlates positively with both anti-Pf circumsporozoite protein (CSP) IgG and CD8 + CD69+ effector memory T cell levels consistent with partial pre-erythrocytic immunity. IFNγ levels decrease significantly during the participants' second exposure to high blood stage parasitemia and could contribute to the decrease in symptoms. In contrast, CD4-CD8 + T cells expressing CXCR5 and the inhibitory receptor, PD-1, increase significantly after subsequent Pf exposures, possibly dampening the memory response and interfering with the generation of robust sterilizing immunity.
Topics: Humans; Malaria, Falciparum; Plasmodium falciparum; Male; Protozoan Proteins; Animals; Adult; Antibodies, Protozoan; Interferon-gamma; Female; Immunoglobulin G; Young Adult; CD8-Positive T-Lymphocytes; Mosquito Vectors; Anopheles
PubMed: 38890271
DOI: 10.1038/s41467-024-49041-2 -
Expert Review of Vaccines 2024Malaria continues to remain a major global health problem with nearly a quarter of a billion clinical cases and more than 600,000 deaths in 2022. There has been... (Review)
Review
INTRODUCTION
Malaria continues to remain a major global health problem with nearly a quarter of a billion clinical cases and more than 600,000 deaths in 2022. There has been significant progress toward vaccine development, however, poor efficacy of approved vaccines requiring multiple immunizing doses emphasizes the need for continued efforts toward improved vaccines. Progress to date, nonetheless, has provided impetus for malaria elimination.
AREAS COVERED
In this review we will focus on diverse immune mechanisms targeting gametocytes in the human host and gametocyte-mediated malaria transmission via the mosquito vector.
EXPERT OPINION
To march toward the goal of malaria elimination it will be critical to target the process of malaria transmission by mosquitoes, mediated exclusively by the sexual stages, i.e. male, and female gametocytes, ingested from infected vertebrate host. Studies over several decades have established antigens in the parasite sexual stages developing in the mosquito midgut as attractive targets for the development of transmission blocking vaccines (TBVs). Immune clearance of gametocytes in the vertebrate host can synergize with TBVs and directly aid in maintaining effective transmission reducing immune potential.
Topics: Humans; Malaria Vaccines; Animals; Malaria; Vaccine Development; Mosquito Vectors; Plasmodium
PubMed: 38888098
DOI: 10.1080/14760584.2024.2369583 -
Infection and Immunity Jun 2024Human babesiosis is a malaria-like illness caused by protozoan parasites of the genus . is responsible for most cases of human babesiosis in the United States,...
Human babesiosis is a malaria-like illness caused by protozoan parasites of the genus . is responsible for most cases of human babesiosis in the United States, particularly in the Northeast and the Upper Midwest. is primarily transmitted to humans through the bite of infected deer ticks but also through the transfusion of blood components, particularly red blood cells. There is a high risk of severe and even fatal disease in immunocompromised patients. To date, serology testing relies on an indirect immunofluorescence assay that uses the whole antigen. Here, we report the construction of phage display cDNA libraries from -infected erythrocytes as well as human reticulocytes obtained from donors with hereditary hemochromatosis. Plasma samples were obtained from patients who were or had been infected with . The non-specific antibody reactivity of these plasma samples was minimized by pre-exposure to the human reticulocyte library. Using this novel experimental strategy, immunoreactive segments were identified in three antigens termed BmSA1 (also called BMN1-9; BmGPI12), BMN1-20 (BMN1-17; Bm32), and BM4.12 (N1-15). Moreover, our findings indicate that the major immunoreactive segment of BmSA1 does not overlap with the segment that mediates BmSA1 binding to mature erythrocytes. When used in combination, the three immunoreactive segments form the basis of a sensitive and comprehensive diagnostic immunoassay for human babesiosis, with implications for vaccine development.
PubMed: 38884473
DOI: 10.1128/iai.00215-24