Human Cases Research Articles

Serosurvey of canine leishmaniasis in five departments near an identified human clinical case in Marseille (France)

Leishmania infantum is a protozoan parasite of the family Trypanosomatidae, transmitted by the bite of phlebotomine sand flies (Diptera: Psychodidae). It is responsible for human and canine leishmaniasis in countries bordering the Mediterranean basin. Here we describe a clinical case of human cutaneous leishmaniasis in a 76-year-old female patient living in Marseille. Upon interrogation, the patient had no history of recent travel or contact with animals. The study involved clinical, serological, and molecular investigation of the occurrence of Leishmania infection in 718 dogs from five departments within a 130 km radius perimeter around Marseille. Five dogs showed signs of moderate leishmaniasis. Additionally, the serological survey of dogs revealed a global seroprevalence of 5.1%, with a significantly different prevalence in the Vaucluse department. Molecular analysis and phylogenetic studies highlighted the close relatedness of Leishmania strains between human and canine hosts with 99.6% of identity, indicating local transmission. The findings underscore the importance of serological surveillance in dogs and human. In a One Health approach, it is necessary to continue investigating Leishmania infection in all potential reservoirs, especially for zoonotic L. infantum in wildlife (red foxes, leporids, rodents, etc.) but also in dogs, cats, and equids.

Establishing a surveillance programme for Salmonella Dublin in Austrian dairy herds by comparing herd-level vs. individual animal detection methods

Due to its increasing occurrence in cattle farms in various countries, leading to significant economic losses in affected livestock, Salmonella enterica subspecies enterica serovar Dublin (S. Dublin) has become a highly investigated pathogen in cattle production. In Austria, there have been occasional human cases of S. Dublin as well as an increase in laboratory-confirmed cases in cattle, indicating the need for a screening programme to determine the current status in Austria. The aims of this study were, firstly, to determine the seroprevalence of S. Dublin in dairy herds through bulk milk screenings in two federal states (Salzburg, Tyrol) of Austria. Secondly, the study aimed to identify the infection status of the herds through individual animal and herd level detection, comparing microbiological, molecular and serological detection methods. The results of the study will allow the development of a sampling strategy for a surveillance programme in Austria.A total of 6973 dairy farms were tested through serological bulk milk screening. The seroprevalence for the federal state of Tyrol was 14.8 % and for Salzburg it was 18.2 %, resulting in an average seroprevalence of 16.5 %. At an individual animal level, 205 (11.3 %) animals tested positive for shedding of S. Dublin in the faeces through microbiological detection, and 268 (17.0 %) animals had positive values (ct value ≤ 38) by qPCR. The association between microbiological and molecular detection was statistically significant (p < 0.001), with a calculated kappa value of 0.65 ± 0.27 (p ≤ 0.001), assuming a substantial level of agreement. In 17 herds, where an individual animal tested positive for shedding of S. Dublin, environmental sampling and testing were carried out. At a herd level 16 (94.1 %) out of the 17 participating herds, tested positive for S. Dublin either microbiologically or by molecular assay in boot swab samples. Bulk milk samples from 14 out of the 17 participating herds were analysed for antibodies to S. Dublin and 12 samples (85.7 %) were positive. In total 111 (18.9 %) out of 587 blood samples tested positive for S. Dublin antibodies, demonstrating a statistically significant correlation (p < 0.001) both with microbiological (κ = 0.32 ± 0.49; p ≤ 0.001) and molecular (κ=0.23 ± 0.06; p ≤ 0.001) findings.It was possible to identify S. Dublin by culture from boot swabs in 14 (82.4 %) out of 17 herds and by molecular assay using qPCR in 15 (88.2 %) out of 17 herds, indicating a suitable sample type for screening on a herd level-basis for acute infections, but not for identifying chronic infections or asymptomatic carriers. Other environmental samples, such as sponge-sticks, are only suitable to a limited extent for the detection of S. Dublin. The results of this study demonstrate a moderate S. Dublin prevalence in dairy herds in the selected Austrian regions, signalling further screening and management programmes for the future.

H5 and H9 avian influenza - potential re-emergent zoonotic threats to humans.

This review aims to discuss the current state of human infections with Avian Influenza A (H5) and (H9) viruses, to support awareness of the global epidemiology among clinicians and public health professionals interested in emerging respiratory infections. Among increasing numbers of detections in avian species of Avian Influenza A(H5N1) clade 2.3.4.4b globally, reported human cases of severe infection have been rare.Enhanced surveillance of persons exposed to avian species infected with Influenza A (H5N1) clade 2.3.4.4b in different countries has identified small numbers of asymptomatic individuals with Avian Influenza A (H5N1) detected by PCR from the upper respiratory tract; some of these instances have been considered to represent contamination rather than infection.There have also been recent sporadic human cases of Avian Influenza A(H9N2) internationally, including in China and Cambodia. Human infections with Avian Influenza A(H5) and (H9) viruses remain of interest as an emerging infection both to clinicians and public health professionals. While maintaining effective surveillance is essential, one health strategies to control infection in avian species will be key to mitigating these risks.

Human Brucellosis in Iraq: Spatiotemporal Data Analysis From 2007-2018.

Brucellosis is both endemic and enzootic in Iraq, resulting in long-term morbidity for humans as well as economic loss. No previous study of the spatial and temporal patterns of brucellosis in Iraq was done to identify potential clustering of cases. This study aims to detect the spatial and temporal distribution of human brucellosis in Iraq and identify any changes that occurred from 2007 to 2018. A descriptive, cross-sectional study was conducted using secondary data from the Surveillance Section at the Communicable Diseases Control Center, Public Health Directorate, Ministry of Health in Iraq. The trends of cases by sex and age group from 2007 to 2018 were displayed. The seasonal distribution of the cases from 2007 to 2012 was graphed. We calculated the incidence of human brucellosis per district per year and used local Getis-Ord Gi* statistics to detect the spatial distribution of the data. The data were analyzed using Microsoft Excel and GeoDa software. A total of 51,508 human brucellosis cases were reported during the 12-year study period, with some missing data for age groups. Human brucellosis persisted annually in Iraq across the study period with no specific temporal clustering of cases. In contrast, spatial clustering was predominant in northern Iraq. There were significant differences in the geographic distribution of brucellosis. The number of cases is the highest in the north and northeast regions of the country, which has borders with nearby countries. In addition, people in these areas depend more on locally made dairy products, which can be inadequately pasteurized. Despite the lack of significant temporal clustering of cases, the highest number of cases were reported during summer and spring. Considering these patterns when allocating resources to combat this disease, determining public health priorities, and planning prevention and control strategies is important.

A(H2N2) and A(H3N2) influenza pandemics elicited durable cross-reactive and protective antibodies against avian N2 neuraminidases

Human cases of avian influenza virus (AIV) infections are associated with an age-specific disease burden. As the influenza virus N2 neuraminidase (NA) gene was introduced from avian sources during the 1957 pandemic, we investigate the reactivity of N2 antibodies against A(H9N2) AIVs. Serosurvey of healthy individuals reveal the highest rates of AIV N2 antibodies in individuals aged ≥65 years. Exposure to the 1968 pandemic N2, but not recent N2, protected against A(H9N2) AIV challenge in female mice. In some older adults, infection with contemporary A(H3N2) virus could recall cross-reactive AIV NA antibodies, showing discernable human- or avian-NA type reactivity. Individuals born before 1957 have higher anti-AIV N2 titers compared to those born between 1957 and 1968. The anti-AIV N2 antibodies titers correlate with antibody titers to the 1957 N2, suggesting that exposure to the A(H2N2) virus contribute to this reactivity. These findings underscore the critical role of neuraminidase immunity in zoonotic and pandemic influenza risk assessment.

The microbiological quality of flour products in the UK with respect to Salmonella and Shiga-toxin-producing E. coli (STEC).

To investigate the possible contamination of raw flour and raw flour-based products, such as pancake/batter mixes, with Salmonella, generic E. coli and STEC. Samples included flours available for sale in the UK over a period of four months (January to April 2020). The Bread and Flour regulations, 1998 state the permitted ingredients in flour and bread but it does not specify the regular monitoring of the microbiological quality of flour and flour-based products. Samples of raw flour were collected by local authority sampling officers in accordance with current guidance on microbiological food sampling then transported to the laboratory for examination. Microbiological testing was performed to detect Salmonella spp., generic E. coli and Shiga-toxin-producing Escherichia coli (STEC) characterised for the presence of STEC virulence genes: stx1, stx2 and subtypes, eae, ipah, aggR, lt, sth and stp, using molecular methods (PCR). Of the 882 flours sampled, the incidence of Salmonella was 0.1% (a single positive sample that contained multiple ingredients such as flour, dried egg and dried milk, milled in the UK), and 68 samples (7.7%) contained generic E. coli at a level of >20 CFU/g. Molecular characterisation of flour samples revealed the presence of the Shiga-toxin (stx) gene in 10 samples (5 imported and 5 from the UK) (1.1%), from which STEC was isolated from 7 samples (0.8%). Salmonella and STEC isolates were sequenced to provide further characterisation of genotypes and to compare to sequences of human clinical isolates held in the UKHSA archive. Using our interpretive criteria based on genetic similarity, none of the STEC flour isolates correlated with previously observed human cases, while the singular Salmonella serotype Newport isolate from the mixed ingredient product was similar to a human case in 2019, from the UK, of S. Newport. Although there have been no reported human cases of STEC matching the isolates from these flour samples, some of the same serotypes and stx subtypes detected are known to have caused illness in other contexts. Results indicate that while the incidence was low, there is a potential for the presence of Salmonella and STEC in flour, and a genetic link was demonstrated between a Salmonella isolate from a flour-based product and a human case of salmonellosis.

Whole genome sequencing identifies a homozygous splicing variant in TDRKH segregating with non-obstructive azoospermia in an Iranian family.

Non-obstructive azoospermia (NOA) resulting from primary spermatogenic failure represents one of the most severe forms of male infertility, largely because therapeutic options are very limited. Beyond their diagnostic value, genetic tests for NOA also hold prognostic potential. Specifically, genetic diagnosis enables the establishment of genotype-testicular phenotype correlations, which, in some cases, provide a negative predictive value for testicular sperm extraction (TESE), thereby preventing unnecessary surgical procedures. In this study, we employed whole-genome sequencing (WGS) to investigate two generations of an Iranian family with NOA and identified a homozygous splicing variant in TDRKH (NM_001083965.2: c.562-2A>T). TDRKH encodes a conserved mitochondrial membrane-anchored factor essential for piRNA biogenesis in germ cells. In Tdrkh knockout mice, de-repression of retrotransposons in germ cells leads to spermatogenic arrest and male infertility. Previously, our team reported TDRKH involvement in human NOA cases through the investigation of a North African cohort. This current study marks the second report of TDRKH's role in NOA and human male infertility, underscoring the significance of the piRNA pathway in spermatogenesis. Furthermore, across both studies, we demonstrated that men carrying TDRKH variants, similar to knockout mice, exhibit complete spermatogenic arrest, correlating with failed testicular sperm retrieval.

Integrated Information for Pathogenicity and Treatment of Spiroplasma.

Spiroplasma, belonging to the class Mollicutes, is a small, helical, motile bacterium lacking a cell wall. Its host range includes insects, plants, and aquatic crustaceans. Recently, a few human cases of Spiroplasma infection have been reported. The diseases caused by Spiroplasma have brought about serious economic losses and hindered the healthy development of agriculture. The pathogenesis of Spiroplasma involves the ability to adhere, such as through the terminal structure of Spiroplasma, colonization, and invasive enzymes. However, the exact pathogenic mechanism of Spiroplasma remains a mystery. Therefore, we systematically summarize all the information about Spiroplasma in this review article. This provides a reference for future studies on virulence factors and treatment strategies of Spiroplasma.

Comparative genomics analysis of Mycoplasma capricolum subsp. capricolum MOR20

Mycoplasma capricolum subsp. capricolum (Mcc) is an etiological agent of Contagious Agalactia (CA) in small ruminants and belongs to Mycoplasma mycoides cluster. Until today, six strains genomes and candidates of Mcc were sequenced in Germany, USA, France and China. The aim of the present study is to analyze the genomic sequence of Mcc MOR20 strain and to compare it with the other sequenced strains. Indeed, the genome sequence of Mcc MOR20 strain was obtained using Illumina NovaSeq 6000 platform. NGS sequencing reads were assembled de novo using CLC genomics v12 (Qiagen). The variant calling on MOR20 strain was conducted using SNIPPY tools. The phylogenomic analysis of Mcc MOR20 strain was performed using BuscoPhylo pipeline. Thus, the genome of Mcc MOR20 characterized by 960,401 bp and encoded for 820 protein-coding genes, 15 rRNA genes (5S, 16S, and 23S), 34 tRNA genes, and three ncRNA genes. In addition, Mcc MOR20 is genetically closer to Mcc isolate human case with percentage of 98.58 %. In addition, the Mcc MOR20 show a genomic relationship with Mccp clade, and they share the same must of potential virulence genes that were identified, including variable surface lipoproteins and metabolic enzymes. The results of this study could be of interest for contagious agalactia vaccine development and the conserved gene might be taken as candidate for new markers for Mcc diagnosis.

Avian influenza overview March-June 2024.

Between 16 March and 14 June 2024, 42 highly pathogenic avian influenza (HPAI) A(H5) virus detections were reported in domestic (15) and wild (27) birds across 13 countries in Europe. Although the overall number of detections in Europe has not been this low since the 2019-2020 epidemiological year, HPAI viruses continue to circulate at a very low level. Most detections in poultry were due to indirect contact with wild birds, but there was also secondary spread. Outside Europe, the HPAI situation intensified particularly in the USA, where a new A(H5N1) virus genotype (B3.13) has been identified in >130 dairy herds in 12 states. Infection in cattle appears to be centred on the udder, with milk from infected animals showing high viral loads and representing a new vehicle of transmission. Apart from cattle, HPAI viruses were identified in two other mammal species (alpaca and walrus) for the first time. Between 13 March and 20 June 2024, 14 new human cases with avian influenza virus infection were reported from Vietnam (one A(H5N1), one A(H9N2)), Australia (with travel history to India, one A(H5N1)), USA (three A(H5N1)), China (two A(H5N6), three A(H9N2), one A(H10N3)), India (one A(H9N2)), and Mexico (one fatal A(H5N2) case). The latter case was the first laboratory-confirmed human infection with avian influenza virus subtype A(H5N2). Most of the human cases had reported exposure to poultry, live poultry markets, or dairy cattle prior to avian influenza virus detection or onset of illness. Human infections with avian influenza viruses remain rare and no human-to-human transmission has been observed. The risk of infection with currently circulating avian A(H5) influenza viruses of clade 2.3.4.4b in Europe remains low for the general public in the EU/EEA. The risk of infection remains low-to-moderate for those occupationally or otherwise exposed to infected animals or contaminated environments.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis

Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. The Key Research and Development Program of China.

Global epidemiology of severe fever with thrombocytopenia syndrome virus in human and animals: a systematic review and meta-analysis

Since the initial identification of the Severe Fever with Thrombocytopenia Syndrome (SFTS) in ticks in rural areas of China in 2009, the virus has been increasingly isolated from a diverse array of hosts globally, exhibiting a rising trend in incidence. This study aims to conduct a systematic analysis of the temporal and spatial distribution of SFTS cases, alongside an examination of the infection rates across various hosts, with the objective of addressing public concerns regarding the spread and impact of the disease. In this systematic review and meta-analysis, an exhaustive search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Medline, CNKI, WanFang, and CQVIP. The literature search was confined to publications released between January 1, 2009, and May 29, 2023. The study focused on collating data pertaining to animal infections under natural conditions and human infection cases reported. Additionally, species names were unified using the National Center for Biotechnology Information (NCBI) database. The notification rate, notification death rate, case fatality rate, and infection rates (or MIR) were assessed for each study with available data. The proportions were pooled using a generalized linear mixed-effects model (GLMM). Meta-regressions were conducted for subgroup analysis. This research has been duly registered with PROSPERO, bearing the registration number CRD42023431010. We identified 5492 studies from database searches and assessed 238 full-text studies for eligibility, of which 234 studies were included in the meta-analysis. For human infection data, the overall pooled notification rate was 18.93 (95% CI 17.02-21.05) per ten million people, the overall pooled notification deaths rate was 3.49 (95% CI 2.97-4.10) per ten million people, and the overall pooled case fatality rate was 7.80% (95% CI 7.01%-8.69%). There was an increasing trend in notification rate and deaths rate, while the case fatality rate showed a significant decrease globally. Regarding animal infection data, among 94 species tested, 48 species were found to carry positive nucleic acid or antibodies. Out of these, 14 species were classified under Arthropoda, while 34 species fell under Chordata, comprising 27 Mammalia and 7 Aves. This systematic review and meta-analysis present the latest global report on SFTS. In terms of human infections, notification rates and notification deaths rates are on the rise, while the case fatality rate has significantly decreased. More SFTSV animal hosts have been discovered than before, particularly among birds, indicating a potentially broader transmission range for SFTSV. These findings provide crucial insights for the prevention and control of SFTS on a global scale. None.

Sequence analysis of microbiota in clinical human cases with diabetic foot ulcers from China

BackgroundDiabetic foot ulcers (DFU) seriously threaten the health and quality of life of patients. The microbiota is the primary reason for the refractory and high recurrence of DFU. This study aimed to determine the wound microbiota at different DFU stages. MethodsWound samples were collected from 48 patients with DFU and divided into three phases: inflammatory (I, n = 49), proliferation (P, n = 22), and remodeling (R, n = 19). The wound samples obtained at different stages were then subjected to 16S rRNA gene sequencing. The number of operational taxonomic units (OTUs) in the different groups was calculated according to the criterion of 97 % sequence similarity. The diversity of the microbiota differentially presented bacterial taxa at the phylum and genus levels, and important phyla and genera in the different groups were further explored. ResultsAfter sequencing, 3351, 925, and 777 OTUs were observed in groups I, P, and R, respectively, and 175 OTUs overlapped. Compared with the inflammatory stage, the α-diversity of wound microbiota at proliferation and remodeling stages was significantly decreased (P < 0.05). At the phylum level, Firmicutes, Proteobacteria, Actinobacteriota, and Bacteroidota were the dominant phyla, accounting for more than 90 % of all the phyla. At the genus level, Random Forest and linear discriminant analysis effect size analyses showed that Peptoniphilus, Lactobacillus, Prevotella, Veillonella, Dialister, Streptococcus, and Ruminococcus were the signature wound microbiota for the inflammatory stage; Anaerococcus, Ralstonia, Actinomyces, and Akkermansia were important species for the proliferation stage; and the crucial genera for the remodeling stage were Enterobacter, Pseudomonas, Sondgrassella, Bifidobacterium, and Faecalibacterium. ConclusionsThere were significant differences in the composition and structure of the wound microbiota in patients with DFU at different stages, which may lay a foundation for effectively promoting wound healing in DFU.

Epidemiology of Q fever in humans in four selected regions, Spain, 2016 to 2022.

BackgroundQ fever is a bacterial zoonosis caused by Coxiella burnetii. Spain has the highest number of notified human cases in Europe. Small ruminants are a key reservoir for the pathogen, transmission from animals to humans is usually airborne.AimWe aimed at exploring temporal and spatial epidemiological patterns of sporadic and outbreak cases of Q fever in four Spanish regions with the highest number of notified cases.MethodsWe extracted data on Q fever cases in the Canary Islands, Basque Country, La Rioja and Navarre between 2016 and 2022 from the Spanish National Epidemiological Surveillance Network. We calculated standardised incidence ratios (SIR), spatial relative risks (sRR) and posterior probabilities (PP) utilising Besag-York-Mollié models.ResultsThere were 1,059 notifications, with a predominance of males aged 30-60 years. In Basque Country, La Rioja and Navarre area, 11 outbreaks were reported, while no in the Canary Islands. A seasonal increase in incidence rates was observed between March and June. In the Canary Islands, elevated sRR was seen in La Palma, Gran Canaria, Lanzarote and Fuerteventura. In Basque Country, La Rioja and Navarre area, the highest sRR was identified in the south of Biscay province.ConclusionGoats were the main source for humans in outbreaks reported in the literature. Seasonal increase may be related to the parturition season of small ruminants and specific environmental conditions. Local variations in sRR within these regions likely result from diverse environmental factors. Future One Health-oriented studies are essential to deepen our understanding of Q fever epidemiology.

Evaluation of the Viral Hemorrhagic Fever Surveillance System in the Assaba region, Mauritania (2020-2022)

Several arboviral diseases have been known to be endemic (e.g., Crimean-Congo hemorrhagic fever, Rift Valley fever) or are emerging (dengue fever, chikungunya, O'nyong-nyong) in human populations in Mauritania, while others have become rare in recent years (e.g. yellow fever). Moreover, domestic animals, especially cattle, camels, goats, and sheep, are also known to be infected with some of these arboviruses (e.g. Crimean-Congo hemorrhagic fever, Rift Valley fever). For these reasons, viral hemorrhagic fever surveillance in Mauritania is part of the Integrated Disease Surveillance and Response (IDSR). However, limited information is available on the efficacy of the viral hemorrhagic fever surveillance system in the Assaba region of Mauritania. The aim of the present study was to assess the performance of the surveillance system, in particular its general utility, simplicity, flexibility, acceptability, and reactivity. A descriptive cross-sectional study was conducted from July to August 2022 in the Assaba region with the objective of evaluating the characteristics of the system by interviewing key actors involved in the surveillance of viral hemorrhagic fevers, with a focus on Rift Valley fever and Crimean-Congo hemorrhagic fever, using questionnaires developed following the guidelines of the Centers for Disease Control and Prevention (Atlanta, Georgia, USA). Data from 2020-2022 on viral hemorrhagic fevers from the National Institute of Public Health laboratory were analyzed. Medians, interquartile ranges, and proportions were calculated using Epi Info® 7.2.5.0 and Excel® 2021. The questionnaire was answered by all twenty-six persons involved in the viral hemorrhagic fever surveillance system in Assaba region. The majority of survey respondents found the system to be useful (51%), simple (63%), acceptable (46%), responsive (64%), and flexible (46%). An analysis of the data revealed a positive predictive value of 28% for Rift Valley Fever. The weekly distribution of cases within the wilaya indicates that the moughataa of Kiffa recorded the highest number of cases in September, with a notable weekly peak during that month in 2020. According to the analysis of the National Institute of Public Health database, cases of viral hemorrhagic fevers were promptly handled. Survey responses and database analysis revealed issues related to data quality and data management mechanisms. These limitations in the surveillance system are likely to be due to insufficient resources and training of the personnel, in particular with regards to data collection and management, which in turn led to incomplete or missing data and invalid data entry. These weak points can be ascribed, at least in part, to financial constraints and inadequate attribution of priority to arboviral diseases. Despite these limitations, disease data generated by the surveillance system were generally reliable. The viral hemorrhagic fever surveillance system in the Assaba region adheres to the organization and functioning of the national viral hemorrhagic fever surveillance system, which is part of the IDSR. The characteristics of utility, simplicity, responsiveness, and flexibility of the viral hemorrhagic fever surveillance system are good, but acceptability and flexibility need further improvement. The earlier the first arboviral human or animal cases are detected, the more likely an active intervention can be organized in response to the emerging epidemic or epizootic and prevent the spread of the disease. An efficient viral surveillance system is the key to reducing the negative impact of arboviral diseases in Assaba region.

Neuropathologically-directed profiling of PRNP somatic and germline variants in sporadic human prion disease.

Creutzfeldt-Jakob Disease (CJD), the most common human prion disease, is associated with pathologic misfolding of the prion protein (PrP), encoded by the PRNP gene. Of human prion disease cases, ~1% were transmitted by misfolded PrP, ~15% are inherited, and ~85% are sporadic (sCJD). While familial cases are inherited through germline mutations in PRNP, the cause of sCJD is unknown. Somatic mutations have been hypothesized as a cause of sCJD, and recent studies have revealed that somatic mutations accumulate in neurons during aging. To investigate the hypothesis that somatic mutations in PRNP may underlie sCJD, we performed deep DNA sequencing of PRNP in 205 sCJD cases and 170 age-matched non-disease controls. We included 5 cases of Heidenhain variant sporadic CJD (H-sCJD), where visual symptomatology and neuropathology implicate focal initiation of prion formation, and examined multiple regions across the brain including in the affected occipital cortex. We employed Multiple Independent Primer PCR Sequencing (MIPP-Seq) with a median depth of >5,000X across the PRNP coding region and analyzed for variants using MosaicHunter. An allele mixing experiment showed positive detection of variants in bulk DNA at a variant allele fraction (VAF) as low as 0.2%. We observed multiple polymorphic germline variants among individuals in our cohort. However, we did not identify bona fide somatic variants in sCJD, including across multiple affected regions in H-sCJD, nor in control individuals. Beyond our stringent variant-identification pipeline, we also analyzed VAFs from raw sequencing data, and observed no evidence of prion disease enrichment for the known germline pathogenic variants P102L, D178N, and E200K. The lack of PRNP pathogenic somatic mutations in H-sCJD or the broader cohort of sCJD suggests that clonal somatic mutations may not play a major role in sporadic prion disease. With H-sCJD representing a focal presentation of neurodegeneration, this serves as a test of the potential role of clonal somatic mutations in genes known to cause familial neurodegeneration.

Resolving Human Rights Violation Cases in Aceh, Indonesia

Penelitian ini bertujuan untuk mengkaji posisi dan peran ulama dalam penyelesaian kasus pelanggaran HAM yang dilakukan Komisi Kebenaran dan Rekonsiliasi (TRC) Aceh. Laporan ini menganalisis keterwakilan ulama di komisioner KKR Aceh, peran mereka dalam rekonsiliasi, dan faktor-faktor yang mempengaruhi peran ulama. Data diperoleh melalui wawancara dan dokumentasi. Data dianalisis menggunakan model Miles dan Huberman. Hasil penelitian menunjukkan bahwa peran ulama dalam rekonsiliasi kasus pelanggaran HAM yang dilakukan KKR Aceh diabaikan. Ulama tidak diwakili oleh komisioner KKR dan tidak berperan penting dalam proses rekonsiliasi. Berkurangnya peran mereka dalam resolusi konflik berkaitan dengan delegitimasi di Aceh. Hal ini terjadi karena kurangnya ulama yang mumpuni dalam menyelesaikan konflik Aceh serta adanya gesekan atau polarisasi di antara mereka. Penyebab lainnya adalah kurangnya perhatian ulama terhadap isu HAM dan munculnya aktor-aktor baru yang mengambil alih peran penyelesaian konflik. Ulama di Aceh dapat menegaskan kembali perannya dalam penyelesaian konflik dengan memulihkan legitimasinya. Mereka harus meningkatkan kualitas dan formasi yang berbasis dayah, memperkuat persatuan, menghindari gesekan dan polarisasi, serta menjaga netralitas. Ulama juga harus meningkatkan keterlibatannya dalam penyelesaian konflik dan isu hak asasi manusia.

In Vitro Efficacy of Silver Carbene Complexes, SCC1 and SCC22, Against Some Enteric Animal Pathogens

Silver carbene complexes (SCCs), a group of novel silver-based compounds capable of gradually ‎releasing ‎silver ions, have shown significant antimicrobial activity against a wide range of ‎bacterial pathogens mainly ‎isolated from human cases. The antimicrobial activity against ‎animal isolated pathogens has yet been done. ‎The in vitro efficacy of two SCCs with different ‎carrier molecules (SCC1 with a methylated caffeine backbone ‎and SCC22 with a ‎dichloroimidazolium backbone) was investigated against three important animal and ‎human ‎pathogen species. SCC1 and SCC22 exhibited bacteriostatic and bactericidal effects against ‎multidrug ‎resistant Salmonella Typhimurium (poultry isolate), E. coli 843 and E. coli 1568 ‎‎(swine isolates), and the ‎poultry field isolates Salmonella Heidelberg, Salmonella Enteritidis, and ‎Salmonella Montevideo with MICs ‎and MBCs ranged from 16-21 µM (6-8 µg/mL) and 16-32 µM ‎‎(6-12 µg/mL), respectively. Clostridium ‎perfringens type A was sensitive to both SCC1 and ‎SCC22 with the MICs being 11 (4 µg/mL) and 21 µM ‎‎(8 µg/mL), respectively. These values were ‎comparable to the MICs and MBCs for silver acetate. The MBCs ‎against C. ‎perfringens was &gt;85 µM for ‎SCCs and &gt;192 µM for silver acetate (&gt;32 µg/mL for all compounds). Ten hours incubation ‎of C. ‎perfringens with ‎‎40 µg/mL of all three products showed down regulation of virulence genes plc and netB, ‎‎suggesting viable cells and silver can modulate the virulence. Treating the C. ‎perfringens with higher ‎concentration (100 ‎‎µg/mL) of each SCC for 10 hours inhibited more bacteria compared to the ‎untreated bacterial cells, however, no ‎differences in the ultrastructure of lysed bacteria were seen ‎and this concentration might not induce viable ‎but non-culturable (VBNC) state as suggested by ‎transmission electron microscopy findings. SCCs showed a ‎broad antimicrobial activity against ‎all bacterial species tested including multidrug resistant pathogens. Both ‎SCCs demonstrated ‎inhibitory effect against the Gram-positive anaerobic C. perfringens type A ‎which ‎could have a high accumulation capacity for silver ion. These data suggest that SCCs may ‎represent a ‎novel class of broad-spectrum antimicrobial agents, which may be used to reduce the ‎burden of pathogenic ‎bacteria in the gastrointestinal tract of poultry‎‎‎.

VG111: A novel formulation demonstrating clinical evidence of anti-pathogenic activity and accelerated wound healing in humans and companion animals

Objectives: The increasing incidence of chronic wounds such as diabetic foot ulcers and pressure ulcers, often compounded by bacterial infections and biofilm formation, presents significant challenges in wound management. Despite advancements in wound care products and a better understanding of molecular wound repair mechanisms, the treatment of chronic ulcerating conditions remains incomplete. VG111, a novel natural product formulation, emerges as a promising therapeutic candidate addressing the need for an effective wound healing agent with antimicrobial and tissue regenerative properties. Materials and Methods: A thorough evaluation of VG111 included antimicrobial assays to determine its minimum inhibitory concentration against an array of pathogens, assessment of its biofilm disruption capabilities, investigation into its profibrogenic activity through scratch assays, and analysis of its immunomodulatory effects on macrophage-derived cytokines. Quality consistency was ensured by high-performance liquid chromatography fingerprinting, while clinical applicability was assessed through observations in canine and human wound healing cases. Statistical Analysis: The cytotoxic effects of VG111 were assessed using a Two-way ANOVA, indicating no significant cytotoxicity at the tested concentration (Column factor p&lt;0.0001). Results: VG111 demonstrated potent antimicrobial action with effective concentrations ranging from 2.5% to 5.0% v/v, targeting resistant strains of Methicillin-resistant Staphylococcus aureus, colistin-resistant Escherichia coli, Acinetobacter baumannii, and other priority pathogens. It showed biofilm clearance, enhanced fibroblast migration, and a favorable immunomodulatory profile by reducing inflammatory cytokines in vitro. In vivo applications corroborated these findings, with significant wound healing observed in both veterinary and clinical settings, negating the need for additional antibiotics. Conclusions: The study emphasized on VG111 as a robust wound healing agent with significant antimicrobial and biofilm-disrupting properties. Its broad-spectrum efficacy against critical pathogens and ability to promote tissue regeneration mark it as a promising avenue in the management of complex chronic wounds, meriting further clinical exploration.

One Health Approach to Toxoplasmosis: Owner and Dog Seropositivity as Spatial Indicators of Risk Areas for Acquired, Gestational and Congenital Transmission.

Toxoplasmosis has been of public health concern due to direct associations with socioeconomic vulnerability and inadequate living conditions. Accordingly, the present study aimed to assess antibodies against T. gondii, historical reported toxoplasmosis cases and associated socio-environmental risk factors in Pinhais, a full urban area of Curitiba, currently the eighth biggest metropolitan area of Brazil. Anti-Toxoplasma gondii antibodies were assessed by an indirect immunofluorescence reaction (RIFI). Owner and dog samples were also tested by IFAT to anti-Leishmania spp. and anti-Trypanosoma cruzi antibodies. Overall, 20/135 (14.8%) persons and 13/133 (9.8%) dogs from 25 different households were considered seropositive to T. gondii. All samples were seronegative to Leishmania spp. and Trypanosoma cruzi. Although no significant covariates were found in the regression model, statistically associated risk factors in the bivariate analysis included no public water use (p = 0.016) and drinking raw milk (p = 0.041) for owners, and obesity (p = 0.028) and tick infestation (p = 0.03) for dogs. In addition, a spatial cluster of T. gondii seropositivity for both owners and their dogs overlapped the location of historic reported cases of human acquired, gestational and congenital toxoplasmosis. Finally, the results herein showed tick infestation as an indicator of socio-environmental risk for T. gondii exposure in the household environment, and dogs may be used as sentinels for human toxoplasmosis cases.