Explore the vast range of titles available.

Nanoparticle vaccines usually prime stronger immune responses than soluble antigens. Within this class of subunit vaccines, the recent development of computationally designed self-assembling two-component protein nanoparticle scaffolds provides a powerful and versatile platform for displaying multiple copies of one or more antigens. Here we report the generation of three different nanoparticle immunogens displaying 60 copies of p67C, an 80 amino acid polypeptide from a candidate vaccine antigen of Theileria parva , and their immunogenicity in cattle. p67C is a truncation of p67, the major surface protein of the sporozoite stage of T. parva , an apicomplexan parasite that causes an often-fatal bovine disease called East Coast fever (ECF) in sub-Saharan Africa. Compared to I32-19 and I32-28, we found that I53-50 nanoparticle scaffolds displaying p67C had the best biophysical characteristics. p67C-I53-50 also outperformed the other two nanoparticles in stimulating p67C-specific IgG1 and IgG2 antibodies and CD4 + T-cell responses, as well as sporozoite neutralizing capacity. In experimental cattle vaccine trials, p67C-I53-50 induced significant immunity to ECF, suggesting that the I53-50 scaffold is a promising candidate for developing novel nanoparticle vaccines. To our knowledge this is the first application of computationally designed nanoparticles to the development of livestock vaccines.

BackgroundIntestinal parasites are a major public health problem in the developing world and have attracted increasing levels of interest from health researchers over the past decade. Epidemiology-based studies have shown that the prevalence of intestinal parasites is high and they frequently recur in regions with poor sanitation and inadequate sewerage facilities. In this study, we determined the prevalence of intestinal parasites, their egg intensities per sample, and associated risk factors in an informal settlement.MethodsThis was a cross-sectional study conducted in three randomly selected public primary schools located in the informal settlements of Nakuru town. A total of 248 stool samples were collected from asymptomatic pupils and screened, using the Kato Katz technique, for infections caused by soil-transmitted helminths (STH). A random subset of stool samples (n=96) was also screened by polymerase chain reaction (PCR) to detect intestinal protozoa. Socio-demographic variables were collected using a pre-tested structured questionnaire; these data were analysed to identify risk factors for infection. ResultsThe overall prevalence of intestinal parasites was 17.3% (43/248 pupils). The overall prevalence of both STH and intestinal protozoan parasites was 1.2% and 41.7%, respectively. The most commonly diagnosed STH infection was Trichuris trichiura (1.2%), followed by hookworms (0.4%) and Ascaris lumbricoides (0.4%). The prevalence of intestinal protozoan parasites ranged from 0% to 38.5% and included Entamoeba histolytica, Entamoeba hartmanni, Entamoeba dispar, Giardia intestinalis, and Entamoeba coli. All infections were light, with an egg intensity <100 for each of the STH infections. The prevalence of multiple infections, including intestinal protozoan parasites, was 5.2% (n=5) and 0.4% (n=1) for STH in the subset samples. Finally, our analysis identified several significant risk factors for intestinal parasitic infections, including goat rearing (p=0.046), living in a home with an earthen floor (p=0.022), the number of rooms in the household (p=0.035), and the source of food (p=0.016). ConclusionThe low prevalence of intestinal parasites in the informal settlements of Nakuru may be attributed to improvements in hygiene and sanitation, deworming, and general good health practices that are facilitated by the Department of Public Health.

Background: Immune correlates of protection are ideal tools to predict treatment or vaccine efficacy. However, the accuracy of the immune correlate and the capability to robustly predict the outcome of a vaccine candidate are determined by the performance of the in vitro immunoassay used. Several Theileria parva sporozoite seroneutralization assays have previously been used to assess antibody functional activities; however, a common limitation has been the need for fresh material, target cells and sporozoites, and operator-to-operator bias. An improved assay represents a positive step toward overcoming challenges associated with variability and it might provide a more reliable means of establishing an immune correlate with protection after sub-unit vaccine administration. Methods: Herein, we describe key improvements, among them, (1) the use of frozen parasites and target cells to avoid batch-to-batch variations and (2) the development of a new assay read-out based on the detection of infected cells through flow cytometry, instead of the use of Giemsa staining and microscopic evaluation, in order to improve the reproducibility of the results. Results: The improved seroneutralization assay is not only able to detect the individual neutralizing capacity of antibodies; it also detects the additive effect of antibody combinations. Conclusions: This effect is described for the first time in Theileria parva and is of great interest for new antigen discovery and/or the epitope discovery of already known antigens like p67, opening a new avenue for the identification of ECF immune correlates of protection and the in vitro down-selection of new Theileria parva vaccine candidates, thereby contributing to reducing the use of animals in challenge experiments.

African swine fever virus (ASFV) causes a severe hemorrhagic disease in pigs, leading to up to 100% case fatality. The virus May persist on solid surfaces for long periods; thus, fomites, such as contaminated clothing, footwear, farming tools, equipment, and transport vehicles, May contribute to the indirect transmission of the virus. Here, a plastic surface functionalized with tall oil rosin was tested against ASFV. The rosin-functionalized plastic reduced ASFV infectious virus titers by 1.3 log 10 after 60 min of contact time and killed all detectable viruses after 120 min, leading to a ~ 6 log 10 reduction. In contrast, the infectious virus titer of ASFV in contact with low-density polyethylene (LDPE) plastic reduced <1 log 10 after 120 min. Transmission electron microscopy (TEM) showed significant morphological changes in the virus after 2 h of contact with the rosin-functionalized plastic surface, but no changes were observed with the LDPE plastic. The use of antiviral plastic in the farming sector could reduce the spread of ASFV through fomites and could thus be part of an integrated program to control ASFV.

The intestinal roundworm Heligmosomoides bakeri causes chronic infection in susceptible (C57Bl/6) mice; however, repeat (trickle) infection confers immunity and facilitates worm clearance. We previously showed that this acquired immunity is associated with a strong Th2 response, notably the enhanced production of intestinal granulomas. Here we demonstrate that elevated proportions of IgG1-bound eosinophils and macrophages are observed around the developing tissue worms of trickle-infected female C57Bl/6 mice compared to bolus infected animals. Levels of IgG2c, IgA or IgE were not detected in the granulomas. Increased proportions of SiglecF+ and CD206+ cells, but not Ly6G+ and/or NK1.1+ cells, were also found in the granulomas of trickle-infected mice. However, in the natural world rather than the laboratory setting, immune environments are more nuanced. We examined the impact of a mixed immune environment on trickle infection-induced immunity, using a pre-infection with Toxoplasma gondii. The mixed immune environment resulted in fewer and smaller granulomas with a lack of IgG -bound cells as well as reduced proportions of SiglecF+ and CD206+ cells, measured by immunofluorescence and flow cytometry. This was associated with a higher worm burden in the co-infected animals. Our data confirm the importance of intestinal granulomas and parasite-specific antibody for parasite clearance. They highlight why it may be more difficult to clear worms in the field than in the laboratory. Despite decades of research on intestinal parasitic worms, we are still unable to clearly point to why so many people (approximately 1.8 billion) and most livestock/wild animals are infected with these parasites. We have made progress in understanding how the immune system responds to parasitic worms, and how these parasites manipulate our immune system. However, identifying effective clearance mechanisms is complex and context dependent. We have used models of trickle infection (multiple low doses of parasites) and co-infection (two intestinal parasites) to simulate how people/animals get infected in the real world. Using these models, we have confirmed the host/parasite interface (the granuloma) within the intestinal tissue to be key in determining the host’s ability to clear worms. The lack of specific immune cells and antibodies within the granuloma was associated with chronic infection. Our results help explain why intestinal parasitic worms are so prevalent and why it may be difficult to clear worms in natural settings.

In Kenya, limited clinical data on hospitalized malaria patients restricts insights into disease severity and care quality. Using data from the Integrated Facility-based Surveillance (IFBS) system-a sentinel surveillance platform for febrile illnesses across twelve facilities-the assessment focused on risk factors for severe illness and mortality, diagnostic accuracy of microscopy, and adherence to severe malaria treatment guidelines. Analysis of IFBS data obtained from June 2017 to July 2024 was performed using bivariable logistic regression to identify factors linked to severe illness and deaths. Microscopy results were compared with PCR results to assess diagnostic concordance. Evaluation also included whether patients received parasitological confirmation before treatment and if severe cases received IV artesunate followed by artemether-lumefantrine (AL), per standard guidelines. Among 8,487 inpatients, 2,197 (25.9%) tested positive for malaria by either microscopy or rapid diagnostic test; among malaria cases, 713 (32.5%) had severe disease and 16 (0.7%) died. Infants had greater odds of severe illness compared to older ages (odds ratio [OR] was < 1.0 for other age groups compared to ≤ 1 year-old). Both severe illness and death were associated with fever duration of ≥ 5 days compared to ≤ 1 day (ORs: 3.67 and 8.00, respectively) and having been referred from another facility (ORs: 3.01 and 3.15, respectively). Positive microscopy at the health facility was PCR negative in 21% of patients. Only 15% of severe cases were documented to have received both IV artesunate and AL, while 17% received IV quinine. Modifiable factors that suggested delayed care-seeking were associated with worse malaria outcomes in Kenya. Furthermore, gaps in diagnostic accuracy and adherence to treatment protocols for severe malaria were observed during chart review. These findings point to the importance of behaviour change strategies as well as messaging in the community that promote timely care-seeking, referrals and follow-up, especially for the youngest children. Potential malaria over-diagnosis underscores the need for strengthening quality assured microscopy programs with adequate training of microscopists and properly functioning microscopes and reagents, as well as an external quality assurance programme that routinely provide feedback on performance and identify areas for improvement.

Context: Donor funds may be inadequate to support the growing demand for services provided by community-based distribution (CBD) programs. One solution may be to reduce the remuneration of CBD agents, but this approach may lower their productivity. Programs also need to consider reducing other costs, including those for supervision and training. Methods: The cost per agent visit-including costs associated with payments to agents and to supervisors and the costs of training-was calculated for three CBD programs in Tanzania. The output measure was visits in which contraceptives were provided or referrals made for family planning services. Simulations were used to examine the impact of changes in agent remuneration on costs per visit, assuming different levels of spending on training and supervision. Results: The program that paid agents the highest annual compensation (US$398) also had the highest costs per agent ($701), but it had the highest number of visits per agent (425). The program that had the lowest annual payments per agent ($33) also had high costs per agent ($558), because its other costs were high and its agents produced few visits (105). The simulations showed that an increase in the amount spent on agent remuneration reduces costs per visit, because the number of agent visits increases, thereby spreading out supervision and training costs over a larger number of visits. Conclusions: The challenge for CBD programs seeking to reduce their costs is to determine which cost components to decrease so as to minimize any reduction in visits. For example, programs that spend little on compensation might improve their performance by spending more on compensation but less on training or supervision.