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PLoS Neglected Tropical Diseases Mar 2024Control of dog-mediated rabies relies on raising awareness, access to post-exposure prophylaxis (PEP) and mass dog vaccination. To assess rabies awareness in Moramanga...
Control of dog-mediated rabies relies on raising awareness, access to post-exposure prophylaxis (PEP) and mass dog vaccination. To assess rabies awareness in Moramanga district, Madagascar, where rabies is endemic, two complementary quantitative and qualitative approaches were carried out in 2018. In the quantitative approach, a standardized questionnaire was administered to 334 randomized participants living in 170 households located less than 5 km from the anti-rabies treatment center (ARTC) located in Moramanga city (thereafter called the central area), and in 164 households located more than 15 km away from the ARTC in two rural communes (thereafter called the remote area). Logistic regression models were fitted to identify factors influencing knowledge and practice scores. The qualitative approach consisted in semi-structured interviews conducted with 28 bite victims who had consulted the ARTC, three owners of biting dogs, three ARTC staff and two local authorities. Overall, 15.6% (52/334) of households owned at least one dog. The dog-to-human ratio was 1:17.6. The central area had a significantly higher dog bite incidence (0.53 per 100 person-years, 95% CI: 0.31-0.85) compared to the remote area (0.22 per 100 person-years, 95% CI: 0.09-0.43) (p = 0.03). The care pathway following a bite depended on wound severity, how the dog was perceived and its owner's willingness to cover costs. Rabies vaccination coverage in dogs in the remote area was extremely low (2.4%). Respondents knew that vaccination prevented animal rabies but owners considered that their own dogs were harmless and cited access and cost of vaccine as main barriers. Most respondents were not aware of the existence of the ARTC (85.3%), did not know the importance of timely access to PEP (92.2%) or that biting dogs should be isolated (89.5%) and monitored. Good knowledge scores were significantly associated with having a higher socio-economic status (OR = 2.08, CI = 1.33-3.26) and living in central area (OR = 1.91, CI = 1.22-3.00). Good practice scores were significantly associated with living in central area (OR = 4.78, CI = 2.98-7.77) and being aware of the ARTC's existence (OR = 2.29, CI = 1.14-4.80). In Madagascar, knowledge on rabies was disparate with important gaps on PEP and animal management. Awareness campaigns should inform communities (i) on the importance of seeking PEP as soon as possible after an exposure, whatever the severity of the wound and the type of biting dog who caused it, and (ii) on the existence and location of ARTCs where free-of-charge PEP is available. They should also encourage owners to isolate and monitor the health of biting dogs. Above all, awareness and dog vaccination campaigns should be designed so as to reach the more vulnerable remote rural populations as knowledge, good practices and vaccination coverage were lower in these areas. They should also target households with a lower socio-economic status. If awareness campaigns are likely to succeed in improving access to ARTCs in Madagascar, their impact on prompting dog owners to vaccinate their own dogs seems more uncertain given the financial and access barriers. Therefore, to reach the 70% dog vaccination coverage goal targeted in rabies elimination programs, awareness campaigns must be combined with free-of-charge mass dog vaccination.
Topics: Humans; Animals; Dogs; Rabies; Madagascar; Health Knowledge, Attitudes, Practice; Dog Diseases; Rabies Vaccines; Bites and Stings
PubMed: 38551968
DOI: 10.1371/journal.pntd.0012064 -
PLoS Pathogens Mar 2024We recently identified two virulence-associated small open reading frames (sORF) of Yersinia pestis, named yp1 and yp2, and null mutants of each individual genes were...
We recently identified two virulence-associated small open reading frames (sORF) of Yersinia pestis, named yp1 and yp2, and null mutants of each individual genes were highly attenuated in virulence. Plague vaccine strain EV76 is known for strong reactogenicity, making it not suitable for use in humans. To improve the immune safety of EV76, three mutant strains of EV76, Δyp1, Δyp2, and Δyp1&yp2 were constructed and their virulence attenuation, immunogenicity, and protective efficacy in mice were evaluated. All mutant strains were attenuated by the subcutaneous (s.c.) route and exhibited more rapid clearance in tissues than the parental strain EV76. Under iron overload conditions, only the mice infected with EV76Δyp1 survived, accompanied by less draining lymph nodes damage than those infected by EV76. Analysis of cytokines secreted by splenocytes of immunized mice found that EV76Δyp2 induced higher secretion of multiple cytokines including TNF-α, IL-2, and IL-12p70 than EV76. On day 42, EV76Δyp2 or EV76Δyp1&yp2 immunized mice exhibited similar protective efficacy as EV76 when exposed to Y. pestis 201, both via s.c. or intranasal (i.n.) routes of administration. Moreover, when exposed to 200-400 LD50 Y. pestis strain 201Δcaf1 (non-encapsulated Y. pestis), EV76Δyp2 or EV76Δyp1&yp2 are able to afford about 50% protection to i.n. challenges, significantly better than the protection afforded by EV76. On 120 day, mice immunized with EV76Δyp2 or EV76Δyp1&yp2 cleared the i.n. challenge of Y. pestis 201-lux as quickly as those immunized with EV76, demonstrating 90-100% protection. Our results demonstrated that deletion of the yp2 gene is an effective strategy to attenuate virulence of Y. pestis EV76 while improving immunogenicity. Furthermore, EV76Δyp2 is a promising candidate for conferring protection against the pneumonic and bubonic forms of plague.
Topics: Humans; Animals; Mice; Yersinia pestis; Open Reading Frames; Vaccines; Plague Vaccine; Cytokines
PubMed: 38547321
DOI: 10.1371/journal.ppat.1012129 -
MBio Apr 2024Melioidosis, caused by the intracellular bacterial pathogen and Tier 1 select agent (Bp), is a highly fatal disease endemic in tropical areas. No licensed vaccine...
UNLABELLED
Melioidosis, caused by the intracellular bacterial pathogen and Tier 1 select agent (Bp), is a highly fatal disease endemic in tropical areas. No licensed vaccine against melioidosis exists. In preclinical vaccine studies, demonstrating protection against respiratory infection in the highly sensitive BALB/c mouse has been especially challenging. To address this challenge, we have used a safe yet potent live attenuated platform vector, LVS Δ, previously used successfully to develop vaccines against the Tier 1 select agents of tularemia, anthrax, and plague, to develop a melioidosis vaccine. We have engineered melioidosis vaccines (rLVS Δ/Bp) expressing multiple immunoprotective Bp antigens among type VI secretion system proteins Hcp1, Hcp2, and Hcp6, and membrane protein LolC. Administered intradermally, rLVS Δ/Bp vaccines strongly protect highly sensitive BALB/c mice against lethal respiratory Bp challenge, but protection is overwhelmed at very high challenge doses. In contrast, administered intranasally, rLVS Δ/Bp vaccines remain strongly protective against even very high challenge doses. Under some conditions, the LVS Δ vector itself provides significant protection against Bp challenge, and consistent with this, both the vector and vaccines induce humoral immune responses to Bp antigens. Three-antigen vaccines expressing Hcp6-Hcp1-Hcp2 or Hcp6-Hcp1-LolC are among the most potent and provide long-term protection and protection even with a single intranasal immunization. Protection via the intranasal route was either comparable to or statistically significantly better than the single-deletional Bp mutant Bp82, which served as a positive control. Thus, rLVS Δ/Bp vaccines are exceptionally promising safe and potent melioidosis vaccines.
IMPORTANCE
Melioidosis, a major neglected disease caused by the intracellular bacterial pathogen , is endemic in many tropical areas of the world and causes an estimated 165,000 cases and 89,000 deaths in humans annually. Moreover, is categorized as a Tier 1 select agent of bioterrorism, largely because inhalation of low doses can cause rapidly fatal pneumonia. No licensed vaccine is available to prevent melioidosis. Here, we describe a safe and potent melioidosis vaccine that protects against lethal respiratory challenge with in a highly sensitive small animal model-even a single immunization is highly protective, and the vaccine gives long-term protection. The vaccine utilizes a highly attenuated replicating intracellular bacterium as a vector to express multiple key proteins of ; this vector platform has previously been used successfully to develop potent vaccines against other Tier 1 select agent diseases including tularemia, anthrax, and plague.
Topics: Humans; Animals; Mice; Burkholderia pseudomallei; Melioidosis; Tularemia; Anthrax; Plague; Mice, Inbred BALB C; Bacterial Vaccines; Vaccines, Attenuated; Antigens, Bacterial
PubMed: 38511933
DOI: 10.1128/mbio.00186-24 -
Virus Research Jun 2024Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in... (Comparative Study)
Comparative Study
Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we deleted a candidate interferon stimulated gene, Trim14 which resulted in enhanced SARS-CoV titers and clinical disease, suggesting an antiviral role during infection. Importantly, about 60 % of the murine QTL encode susceptibility genes identified as priority candidates from human genome-wide association studies (GWAS) studies after SARS-CoV-2 infection, suggesting that similar selective forces have targeted analogous genes and pathways to regulate Sarbecovirus disease across diverse mammalian hosts. These studies provide an experimental platform in rodents to investigate the molecular-genetic mechanisms by which potential cross mammalian susceptibility loci and genes regulate type-specific and cross-SARS-like group 2B CoV replication, immunity, and pathogenesis in rodent models. Our study also provides a paradigm for identifying susceptibility loci for other highly heterogeneous and virulent viruses that sporadically emerge from zoonotic reservoirs to plague human and animal populations.
Topics: Animals; Humans; Mice; Quantitative Trait Loci; SARS-CoV-2; Virus Replication; Genome-Wide Association Study; COVID-19; Tripartite Motif Proteins; Coronavirus Infections; Disease Models, Animal
PubMed: 38508400
DOI: 10.1016/j.virusres.2024.199357 -
Ecology and Evolution Mar 2024The size and distribution of home ranges reflect how individuals within a population use, defend, and share space and resources, and may thus be an important predictor...
The size and distribution of home ranges reflect how individuals within a population use, defend, and share space and resources, and may thus be an important predictor of population-level dynamics. Eruptive species, such as the house mouse in Australian grain-growing regions, are an ideal species in which to investigate variations in space use and home range overlap between stable and outbreaking populations. In this study, we use spatially explicit capture-recapture models to explore if space use and home range overlap among female mice could serve as indicators of changes in population density leading into summer. Additionally, we assess the sensitivity of space use and home range estimates to reduced recapture rates. Our analysis did not reveal variations in the spring spatial organisation of female mice based on existing capture-mark-recapture data. However, our study highlights the need to balance monitoring efforts within regions, emphasising the importance of exploring studies that can improve spatial recaptures by optimising trapping efforts. This is particularly important in Australian agricultural systems, where varying farm management practices may drive differences in population dynamics.
PubMed: 38505179
DOI: 10.1002/ece3.10843 -
One Health (Amsterdam, Netherlands) Jun 2024Rodents are known reservoirs for a diverse group of zoonotic pathogens that can pose a threat to human health. Therefore, it is crucial to investigate these pathogens to...
Rodents are known reservoirs for a diverse group of zoonotic pathogens that can pose a threat to human health. Therefore, it is crucial to investigate these pathogens to institute prevention and control measures. To achieve this, the current study was conducted to investigate the frequency of different parasites in commensal rodents in Qatar. A total of 148 rodents, including , , and were captured using traps placed in different habitats such as agricultural and livestock farms, residential areas, and other localities. Blood, feces, ectoparasite, and visceral organs were collected for gross, microscopic, immunological, and molecular analysis. The study identified 10 different parasites, including spp., spp., , and . Overall, 62.2% of the rodents tested positive for at least one parasite species. Helminths were found to be the most prevalent parasites (46.0%), followed by ectoparasites (31.8%), and protozoa (10.1%). However, individually, was the most prevalent (31.8%), whereas was the least common (0.7%). The prevalence of and significantly differed between habitats ( < 0.05). The sequence analysis of spp. was closely related to the previously reported in Iran, China, and Mexico. In conclusion, the study identified a diverse range of rodent-borne parasites that are important to public health, with most of them being recorded for the first time among commensal rodents in Qatar.
PubMed: 38496338
DOI: 10.1016/j.onehlt.2024.100708 -
International Journal For Parasitology.... Apr 2024Understanding rodent-ectoparasite interactions and the factors driving them is important in understanding the epidemiology of diseases involving an arthropod vector.... (Review)
Review
Understanding rodent-ectoparasite interactions and the factors driving them is important in understanding the epidemiology of diseases involving an arthropod vector. Fleas are the primary vector for , the bacteria that causes plague and monitoring of flea population is essential for planning the potential mitigation measures to prevent the disease outbreak. In this study, we investigated flea abundance, community structure and the potential factors driving flea infestation in areas with frequent (persistent) and non-frequent plague (non-persistent) outbreaks. We collected fleas from captured rodents in two villages with both forest and farm habitats. We found 352 fleas belonging to 5 species with the most abundant overall (57.10%) and spp the lowest (1.70%). There were no significant differences of flea abundance between study localities, habitats and seasons (p > 0.05) but, flea infestation was significantly positively associated with the persistent locality and with the short rain season (p < 0.05). Further, flea abundance increased significantly with rodent body weight (p < 0.05). Furthermore, we found fleas broadly structured into two communities varying between the dry, long rain and short rain seasons. These findings have important implications for public health, as they may be used to assess and control the risks of plague transmission and other flea borne diseases in the foci.
PubMed: 38495310
DOI: 10.1016/j.ijppaw.2024.100921 -
Translational Cancer Research Feb 2024Due to the implementation of individualized treatment, the majority of gastric cancer patients have a favorable prognosis, but advanced gastric cancer with recurrence...
BACKGROUND
Due to the implementation of individualized treatment, the majority of gastric cancer patients have a favorable prognosis, but advanced gastric cancer with recurrence and distant metastasis still plagues some patients. As a member of the FK506-binding protein (FKBP65) family, there is growing evidence that FKBP10 plays a crucial role in tumorigenesis. However, the role of FKBP10 in the tumor microenvironment (TME) has been a prominent issue.
METHODS
The FKBP10 knockdown efficiency in gastric cancer cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Wound healing and transwell analysis were performed to detect variations in cell invasion and migration. We integrated single-cell and bulk sequencing data to further elaborate the impact of FKBP10 and FKBP10-coexpressed genes (FCGs) in the TME via a variety of bioinformatics approaches.
RESULTS
Here, we found that FKBP10 knockdown inhibited cell invasion and metastasis. FKBP10 was chiefly expressed in inflammatory cancer-associated fibroblasts (iCAFs), and FCGs principally mediated alterations in extracellular matrix (ECM) organization. Besides, according to nine prognosis-related FCGs, two disparate clusters were identified, and differences in tumor immune infiltration characteristics and immunotherapy response between different clusters were investigated.
CONCLUSIONS
Our study provides insights into the expression and function of FKBP10 in the microenvironment of gastric cancer.
PubMed: 38482445
DOI: 10.21037/tcr-23-1484 -
Frontiers in Insect Science 2023In contrast to predictions from nitrogen limitation theory, recent studies have shown that herbivorous migratory insects tend to be carbohydrate (not protein) limited,...
In contrast to predictions from nitrogen limitation theory, recent studies have shown that herbivorous migratory insects tend to be carbohydrate (not protein) limited, likely due to increased energy demands, leading them to preferentially feed on high carbohydrate plants. However, additional factors such as mechanical and chemical defenses can also influence host plant choice and nutrient accessibility. In this study, we investigated the effects of plant protein and carbohydrate availability on plant selection and performance for a migratory generalist herbivore, the Australian plague locust, We manipulated the protein and carbohydrate content of seedling wheat () by increasing the protein:carbohydrate ratio using nitrogen (N) fertilizer, and manipulated the physical structure of the plants by grinding and breaking down cell walls after drying the plants. Using a full factorial design, we ran both choice and no-choice experiments to measure preference and performance. We confirmed locust preference for plants with a lower protein-carbohydrate ratio (unfertilized plants). Unlike previous studies with mature wild grass species, we found that intact plants supported better performance than dried and ground plants, suggesting that cell wall removal may only improve performance for tougher or more carbohydrate-rich plants. These results add to the growing body of evidence suggesting that several migratory herbivorous species perform better on plants with a lower protein:carbohydrate ratio.
PubMed: 38469479
DOI: 10.3389/finsc.2023.1110518