Carriage Of Pathogens Research Articles

To screen or not to screen medical students for carriage of multidrug-resistant pathogens?

The carriage of multidrug-resistant (MDR) pathogens in medical students has not been studied extensively, despite the fact that they are in contact with patients and exposed to a hospital environment. To investigate the intestinal and nasal carriage of MDR pathogens among medical students and its association with their lifestyle and demographic data. In 2021, first- and final-year medical students were invited to the study. Two rectal swabs were used for detection of extended-spectrum β-lactamase (ESBL)-producing, colistin-, tigecycline- or carbapenem-resistant Gram-negative bacteria and vancomycin-resistant enterococci. Nasal swab was used for Staphylococcus aureus culture. S.aureus isolates were characterized by spa typing; Gram-negative resistant isolates and meticillin-resistant S.aureus (MRSA) were subjected to whole-genome short and/or long sequencing. From 178 students, 80 (44.9%) showed nasal carriage of S.aureus; two isolates were MRSA. In rectal swabs, seven ESBL-producing strains were detected. Sixteen students were colonized by colistin-resistant bacteria, three isolates carried the mcr-1 gene (1.7%). The mcr-9 (10.7%, 19/178) and mcr-10 (2.2%, 4/178) genes were detected by quantitative polymerase chain reaction, but only two colistin-susceptible mcr-10-positive isolates were cultured. The S.aureus nasal carriage was negatively associated with antibiotic and probiotic consumption. S.aureus and colistin-resistant bacteria were detected more frequently among students in contact with livestock. Medical students can be colonized by (multi)drug-resistant bacteria with no difference between first- and final-year students. The participation of students in self-screening increases their awareness of possible colonization by resistant strains and their potential transmission due to poor hand hygiene.

Assessing Fungal Plant Pathogen Presence in Irrigation Water from the Rio Grande River in South Texas, USA

Irrigation is important in many crop production systems. However, irrigation water can be a carrier of plant pathogens that can enter the system and spread to fields, resulting in crop damage and yield losses. The Lower Rio Grande Valley of South Texas is an important area for agricultural production which depends on the Rio Grande River as a source of water for irrigation. Thus, the presence of plant pathogens in the Rio Grande River could have important implications for crop productivity in the region. Cultured-based methods and molecular identification methods are used for monitoring plant pathogens in irrigation water. However, these methods are labor-intensive and just detect targeted pathogens. To overcome these limitations, in this study, the ITS2 amplicon metagenomic method was applied for evaluating the fungal diversity, composition, and presence of fungal plant pathogens in irrigation water from the Rio Grande River as it leaves the water reservoir (WR) and it arrives at an irrigation valve at a farm (FA). Results from the Shannon (WR = 4.6 ± 0.043, FA = 3.63 ± 0.13) and Simpson indices (WR = 4.6 ± 0.043, FA = 3.63 ± 0.13) showed that there are significant differences in the fungal diversity and community structure between the two locations and the PCA analysis showed a clear differentiation between both fungal communities. Several OTUs identified in both locations included potential plant pathogens from diverse genera including Cladosporium, Exserohilum, and Nigrospora, while others such as Colletotrichum and Plectosphaerella were found only in one of the two locations assessed. This work indicates that microbes, including plant pathogens, may enter or exit throughout the irrigation-water distribution system, thereby modifying the microbial community composition along the way. Understanding the dynamics of plant pathogen movement in irrigation water systems can help growers identify risk factors to develop measures to mitigate those risks. This study also shows the usefulness of the metagenomic approach for detecting and monitoring plant pathogen in irrigation water.

Longitudinal Assessment of Prevalence and Incidence of Salmonella and Escherichia coli O157 Resistance to Antimicrobials in Feedlot Cattle Sourced and Finished in Two Different Regions of the United States.

The objective was to investigate the influence of cattle origin and region of finishing on the prevalence of Salmonella, Escherichia coli O157:H7, and select antimicrobial resistance in E. coli populations. Yearling heifers (n = 190) were utilized in a 2 × 2 factorial arrangement. After determining fecal Salmonella prevalence, heifers were sorted into one of four treatments: heifers originating from South Dakota (SD) and finished in SD (SD-SD); heifers originating from SD and finished in Texas (SD-TX); heifers originating from TX and finished in SD (TX-SD); and heifers originating from TX and finished in TX (TX-TX). Fecal, pen, and water scum line samples were collected longitudinally throughout the study; hide swab and subiliac lymph node (SLN) samples were collected at study end. A treatment × time interaction was observed (p ≤ 0.01) for fecal Salmonella prevalence, with prevalence being greatest for TX-TX and TX-SD heifers before transport. From day (d) 14 through study end, prevalence was greatest for TX-TX and SD-TX heifers compared with SD-SD and TX-SD heifers. Salmonella prevalence on hides were greater (p ≤ 0.01) for heifers finished in TX compared with SD. Salmonella prevalence in SLN tended (p = 0.06) to be greater in TX-TX and SD-TX heifers compared with TX-SD and SD-SD. Fecal E. coli O157:H7 prevalence had a treatment × time interaction (p = 0.04), with SD-TX prevalence being greater than TX-SD on d 56 and SD-SD and TX-TX being intermediate. A treatment × time interaction was observed for fecal trimethoprim-sulfamethoxazole-resistant and cefotaxime-resistant E. coli O157:H7 prevalence (p ≤ 0.01). Overall, these data suggest that the region of finishing influences pathogenic bacterial shedding patterns, with the initial 14 d after feedlot arrival being critical for pathogen carriage.

Green label marinades: A solution to salmonella and campylobacter in chicken products?

IntroductionThe presence of meat-borne pathogens entering the home remains a concern for consumers, despite advances made in improving antimicrobial interventions and systems within the processing line. Naturally antibacterial food ingredients including citrus juice and essential oils have been proven to inhibit the proliferation of microbial growth with varying success. AimsThis study aims to investigate the antimicrobial and sensory effects of mixtures of essential oils, fruit juices and herbs at established Minimum Inhibitory Concentrations (MICs) for their biopreservative effect on general microbiota of chicken and against chicken challenged with selected pathogenic/surrogate microorganisms. Materials and methodsThree marinade compositions were designed for use on chicken meat; lemon juice, thyme oil and black pepper (M1), lime juice, lemongrass oil and chilli paste (M2), and olive oil, oregano oil, basil oil and garlic paste (M3). These marinades were assessed for antibacterial effects against Salmonella enterica, Campylobacter jejuni and Listeria innocua on marinaded chicken drumsticks stored in aerobic conditions at 4 °C. Consumer tasting sessions were also conducted with a small focus group using selected final marinades. ResultsM1 and M2 were effective at significantly reducing initial pathogen carriage from 6 Log CFU/g to 2 Log CFU/g on refrigerated chicken meat as well as increasing the shelf-life of the product during cold-storage from 2 days to 7 days. However, consumer studies indicate that the flavours these marinades impart to treated products can be strong. ConclusionThese findings indicate that these designed marinades have shown excellent potential to improve food safety as well as shelf-life for the consumer, particularly in settings where food safety is often compromised such as barbecuing or in care settings. However, further recipe optimisation is required to make these marinades acceptable to consumers.

Cooperation between physiological defenses and immune resistance produces asymptomatic carriage of a lethal bacterial pathogen.

Animals evolved two defense strategies to survive infections. Antagonistic strategies include immune resistance mechanisms that operate to kill invading pathogens. Cooperative or physiological defenses mediate host adaptation to the infected state, limiting physiological damage and disease, without killing the pathogen, and have been shown to cause asymptomatic carriage and transmission of lethal pathogens. Here, we demonstrate that physiological defenses cooperate with the adaptive immune response to generate long-term asymptomatic carriage of the lethal enteric murine pathogen, Citrobacter rodentium. Asymptomatic carriage of genetically virulent C. rodentium provided immune resistance against subsequent infections. Immune protection was dependent on systemic antibody responses and pathogen virulence behavior rather than the recognition of specific virulent antigens. Last, we demonstrate that an avirulent strain of C. rodentium in the field has background mutations in genes that are important for LPS structure. Our work reveals insight into how asymptomatic infections can arise mechanistically with immune resistance, mediating exclusion of phenotypically virulent enteric pathogen to promote asymptomatic carriage.

Adhesion of Escherichia coli O157:H7 during sublethal injury and resuscitation: Importance of pili and surface properties

Escherichia coli O157:H7 can recover from sublethally injured (SI) state, which causes threat of foodborne illness. Adhesion plays a key role in the carriage of pathogens in food. In this study, we investigated the adhesion ability of SI and recovered E. coli O157:H7 wildtype and its three pili-deficient mutants (curli, type 1 fimbriae, and type IV pili) on six food-related surfaces. Plate counting was used to determine adhesion population after washing and oscillating the surfaces. Spinach exhibited the stronger adhesion population of E. coli O157:H7 than the other fresh produces (p < 0.05). In addition, at least one key pili dominated adhesion on these surfaces, and curli was always included. The adhesion population and contribution of different types of pili were jointly affected by surface and physiological state. This can be attributed to high hydrophobicity and positive charge density on surface and different expression levels of csgB, fimA, fimC and ppdD in SI and recovered cells. Among glucose, mannose, maltose, fructose, lactose, and sucrose, addition of 0.5% mannose could reduce adhesion of cells at all physiological states on stainless steel. Overall, this research will provide support for controlling adhesion of SI and recovered E. coli O157:H7.

MDB-23. ELP1 GERMLINE DEFICIENCY SENSITIZES THE GRANULE NEURON LINEAGE TO SHH MEDULLOBLASTOMA AND EXPOSES NOVEL THERAPEUTIC VULNERABILITIES

Abstract Germline loss-of-function (LOF) variants in Elongator complex protein 1 (ELP1) are the most prevalent predisposing genetic events in childhood medulloblastoma (MB). ELP1 germline carriers develop SHH-MBs that exhibit coincident somatic PTCH1 mutations and universal loss-of-heterozygosity of the remaining ELP1 allele through chromosome 9q deletion. The molecular, biochemical, and cellular mechanisms by which germline ELP1/Elongator deficiency contribute to SHH-MB tumorigenesis remain largely unknown. Herein, we report that mice engineered to mimic germline Elp1 LOF (i.e., Elp1HET) seen in SHH-MB patients exhibit hallmark features of premalignancy events in cycling cerebellar granule neuron progenitors (GNPs), the lineage-of-origin for SHH-MB. Compared to wild-type counterparts, Elp1HET GNPs exhibit increased replication stress-associated DNA damage, homologous recombination-associated genomic instability, accelerated cell cycle kinetics, reduced p53-dependent apoptosis in response to genotoxic stress, and slowed differentiation. Orthotopic transplantation of Elp1HET GNPs harboring somatic Ptch1 inactivation into the cerebella of immunocompromised mice promotes onset of SHH-MB tumors with incomplete penetrance that exhibit reduced p53 transcriptional activity through a currently unknown mechanism(s). Concomitant Elp1 and Ptch1 gene targeting in p53-null GNPs reproduces highly penetrant cerebellar tumors recapitulating the molecular and phenotypic features of ELP1-associated SHH-MB. Finally, reactivation of the p53 pathway through preclinical treatment with an MDM2 inhibitor promotes cell death and prolongs the survival of patient-derived xenograft tumor (PDX) models harboring deleterious ELP1 mutations. Together, our findings reveal that germline Elp1 LOF heightens genomic instability and malignant transformation in cycling GNPs, providing a mechanistic model for the subgroup-restricted pattern of predisposition associated with pathogenic ELP1 germline carriers. These results provide essential mechanistic insight into the molecular and cellular basis of SHH-MB predisposition driven by ELP1 LOF and nominate therapies that overcome p53 pathway inhibition as a rational treatment option for affected children.

Diversity of True Bugs (Hemiptera: Heteroptera) on Common Ragweed (Ambrosia artemisiifolia) in Southern Slovakia

The common ragweed (Ambrosia artemisiifolia Linnaeus 1800) is an exceptionally invasive species. The information on true bugs occurring on ragweed plants is limited in the invasion region. The objective of this study was to determine the species composition of Heteroptera associated with A. artemisiifolia, to assess their vectoring potential based on a literature review, and to compare species similarity in the surveyed fields. Field surveys were conducted in 2020–2021 at 10 sites in southern Slovakia. Sweeping and visual observations were conducted in field margins, weedy agricultural fields, and mowed meadows infested with A. artemisiifolia. In the study, food specialization, the abundance of individual species, and their assignment to families were precisely determined. The Jaccard similarity index was used to evaluate similarities in species composition among the sites studied. A total of 2496 true bugs were recorded, representing 47 species of Heteroptera from 12 families. The most common phytophagous species were Nysius ericae ericae (Schilling, 1829) (Pentatomomorpha, Lygaeidae), Adelphocoris lineolatus (Goeze, 1778), Lygus rugulipennis (Poppius, 1911), Lygus pratensis (Linnaeus, 1758) (Cimicomorpha, Miridae), and a zoophagous species Nabis (Dolichonabis) limbatus (Dahlbom, 1851) (Cimicomorpha, Nabidae). The species similarities in pair-wise combined localities were low, with a dominance of highly migratory and polyphagous species able to traverse the field from the adjacent landscape. A. artemisiifolia is a known host for plant viruses and phytoplasmas, and several Heteroptera species are carriers of these plant pathogens. Halyomorpha halys was the only detected vector of phytoplasmas, and its abundance on A. artemisiifolia was extremely low.

Epstein–Barr virus downregulates the α7 nicotinic acetylcholine receptor of CD8+ T lymphocytes might associate with coronary artery lesions in Kawasaki disease patients

ObjectivesKawasaki disease (KD) is a systemic vasculitis that is caused by immunological dysregulation in children exposed to pathogens like Epstein–Barr virus (EBV). Myocardial ischemia or infarction due to coronary artery lesions (CALs) might be lethal. However, it is unclear how pathogens, immunomodulation, and CALs interact, particularly in KD patients co-infected with the most widespread virus, EBV. MethodsWe investigated pathogen carriage and fundamental clinical data in 281 KD patients. Immunological differences between CALs and non-CALs in KD patients under different conditions were analyzed. Then, the effect of infection by different pathogens on the immune response was excluded, and most EBV co-infected KD patients were included to assess the incidence of CALs, the level of immune modulation, and regulatory mechanisms in different EBV infection states. ResultsOur results showed multiple pathogenic infections occur in KD patients, with EBV being the most prevalent. The incidence of CALs in the EBV-DNA (+) acute infection group, EBV-DNA (−) acute infection group, and EBV latent infection group was 0 (0/6), 27.27% (3/11) and 41.67% (10/24), respectively. The two groups were younger and had increased IL-6 levels and B cells, decreasing CD8+ T cells than the EBV-DNA (+) acute infection group. Interestingly, the increased B cells were not associated with immunoglobulin release. Additionally, these patients down-regulated α7 nicotinic acetylcholine receptor (α7nAChR) and downstream molecule PI3K/AKT/mTOR while activating the NF-κB. ConclusionPatients with different EBV infection statuses exhibit different incidences of CALs. In acute EBV-DNA (−) infected and latent EBV-infected patients, the number of CD8+ T cells decreased and downregulated CD8+ T cells' α7nAChR and PI3K/AKT/mTOR, which may associate with CALs, while the expression of NF-κB and the pro-inflammatory factor IL-6 was upregulated by inhibiting the anti-inflammatory molecule α7nAChR.

Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral administration of the phage cocktail lowers Kp levels in Kp-colonized germ-free mice and SPF mice, without off-target dysbiosis. Furthermore, we demonstrate that oral and intravenous phage administration successfully suppresses Kp levels and attenuates liver inflammation and disease severity in hepatobiliary injury-prone SPF mice. These results collectively suggest that using a lytic phage cocktail shows promise for targeting Kp in PSC.

Evaluation of the Amount of Some Metals, Fatty Acid and Microbial Load of African Palm Weevil Larvae Rhynchophorus phoenicis (Coleoptera: Curculionidae) Collected from Ondo State, Nigeria

Background: Edible insects are rich in protein, amino acids, fat, vitamins, and trace elements. However, they are the potential carriers of toxicants, allergenic substances, anti-nutrients, and pathogens. The present study aims to determine the proximate and nutritional, fatty acid, metal composition, and microbial load of palm weevil larvae (Rhynchophorus phoenicis Fabricius, (Coleoptera: Curculionidae)), an insect species commonly consumed in Nigeria.&#x0D; Methods: Twenty five R. phoenicis were randomly collected in April, 2021 from different local farms. The insects were exterminated by freezing and thereafter defrosted at room temperature in the laboratory; with the exception of the samples for moisture analysis, they were oven dried to a constant weight at around 65 °C for 24 h, grounded, and analyzed for proximate content, fatty acids, metals, and microbial load following standard laboratory procedures.&#x0D; Results: The results show that R. phoenicis contained 45.60% crude fat, 15.79% crude fiber, and 5.25% crude protein by weight. Linoleic acid, oleic acid, and palmitic acid made up most of the fatty acid concentrations at 54.13, 23.86, and 14.19%, respectively. Iron (Fe) content was the highest metal (4.923 ppm), followed by manganese (Mn; 2.767 ppm) and zinc (Zn; 1.04 ppm). The isolated microorganisms were mold and yeast (5×10-5 Colony Forming Unit (CFU)/g), Staphylococcus sp. (33×10-5 CFU/g), and Micrococcus/Bacillus substilis sp. (5×10-5 CFU/g).&#x0D; Conclusion: The high nutritional composition present in R. phoenicis evaluated in this study, compared to the dietary protein value obtained from other animal food sources, suggests the need for their adoption as animal protein and essential fatty acid sources in human diets.

Ticks of the Ixodidae family as reservoirs and carriers of pathogens of vector-borne infections in the Republic of Guinea

Ticks of the Ixodidae family as reservoirs and carriers of pathogens of vector-borne infections in the Republic of Guinea

Investigation of Upper Respiratory Carriage of Bacterial Pathogens among University Students in Kampar, Malaysia.

The carriage of bacterial pathogens in the human upper respiratory tract (URT) is associated with a risk of invasive respiratory tract infections, but the related epidemiological information on this at the population level is scarce in Malaysia. This study aimed to investigate the URT carriage of Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa among 100 university students by nasal and oropharyngeal swabbing. The presence of S. aureus, K. pneumoniae and P. aeruginosa was assessed via swab culture on selective media and PCR on the resulting isolates. For S. pneumoniae, H. influenzae and N. meningitidis, their presence was assessed via multiplex PCR on the total DNA extracts from chocolate agar cultures. The carriage prevalence of H. influenzae, S. aureus, S. pneumoniae, K. pneumoniae, N. meningitidis and P. aeruginosa among the subjects was 36%, 27%, 15%, 11%, 5% and 1%, respectively, by these approaches. Their carriage was significantly higher in males compared to females overall. The S. aureus, K. pneumoniae and P. aeruginosa isolates were also screened by the Kirby-Bauer assay, in which 51.6% of S. aureus were penicillin-resistant. The outcomes from carriage studies are expected to contribute to informing infectious disease control policies and guidelines.

Knowledge, acceptability and personal attitude toward pre-implantation 1 genetic testing (PGT) and pre-natal diagnosis (PND) for females carrying BRCA pathogenic variant according to fertility preservation experience.

Preimplantation genetic testing (PGT-M) and prenatal diagnosis (PND) followed by medical termination of pregnancy when the fetus is affected are two procedures developed to avoid the transmission of a severe hereditary disease which can be proposed to females that carried BRCA pathogenic variants. These females can also be offered fertility preservation (FP) when diagnosed with cancer or even before a malignancy occurs. The aim of the study was to evaluate the acceptability and personal attitude of women carrying a BRCA mutation toward techniques that can prevent BRCA transmission to their progeny. Female mutated for BRCA1 or BRCA2 were invited to complete an online survey of 49 queries anonymously between June and August 2022. A total of 87 participants responded to the online survey. Overall, 86.2% of women considered that PGT-M should be proposed to all BRCA mutation carriers regardless of the severity of the family history, and 47.1% considered or would consider PGT-M for themselves. For PND, these percentages were lower reaching 66.7% and 29.9%, respectively. Females with personal history of breast cancer or FP achievement were more prone to undergo PND for themselves despite the overall acceptability of this procedure. Among the subgroup who had undergone FP (n = 58), there was no significant difference in acceptance of principle and personal attitude toward PGT-M and PND compared to the group without FP. BRCA pathogenic variants female carriers do need information about reproductive issues, even if they are not prone to undergo PGT-M nor PND for themselves. N/A.

PO-02-126 DEEP PHENOTYPING OF DSP-ENCODED DESMOPLAKIN CARRYING GENOTYPE POSITIVE UKBB SUBJECTS REVEALS ECG CHANGES AS A POSSIBLE EARLY DIAGNOSTIC MARKER OF DISEASE

Arrhythmogenic cardiomyopathy (ACM) is defined by fibrofatty replacement of the ventricular myocardium with loss of myocytes that can result in arrhythmias, sudden cardiac death, and heart failure, especially in young patients. DSP-encoded desmoplakin is a structural protein integral to the cardiac desmosome. Pathogenic variants in DSP are implicated with ACM and renders carriers uniquely susceptible to inflammation which can mimic myocarditis. Thus, there is a need to identify diagnostically informative markers which can help identify individuals with pathogenic DSP variants and ACM. The study aims to use the UK Biobank (UKBB) to describe clinical markers associated with individuals who host DSP variants that can help identify individuals with ACM predisposition. UKBB participants who had undergone whole exome sequencing, ECG, and cardiovascular MRI were selected for study. DSP variants were identified by ClinVar, InterVar, and predicted loss of function in silico modeling, and interpreted manually using ACMG criteria. Variants were matched by age and sex with controls that were genotype negative (G-) for diagnostic cardiomyopathy and ion channelopathy variants. Quantitative ECG and MRI analyses were used with ICD codes to deep phenotype participants. In 122 putative pathogenic DSP carriers (55.52 ± 7.66 years), 11 (9.0%) had atrial fibrillation and/or flutter on ECG analysis compared to 18 (4.9%) in 366 G- controls (55.52 ± 7.64 years). ECG analysis identified smaller S-wave peak amplitude in lead III (192.95 ± 298.66 vs. 287.11 ± 359.35; p=0.009), and in lead aVF (121.87 ± 199.19 vs. 169.00 ± 237.67; p=0.049) among DSP G+ vs. G- participants. Further, T-wave inversion in anterolateral leads was seen in 13 (10.7%) vs. 20 (5.5%) and in inferior leads in 20 (16.4%) vs. 37 (10.1%) in DSP G+ vs. G- controls, respectively. Individuals who host putatively pathogenic DSP variants have distinct ECG markers that may suggest early stages of ACM development, and thus may aid in guiding prognostication. Future steps include stratifying risk by pathogenicity of DSP variants by ACMG criteria to ascertain a more concrete association of likely-pathogenic variants in DSP with atrial fibrillation and/or flutter. Ongoing studies also include further characterization of DSP variants with more detailed MRI analyses with RV/LV characteristics.

Does concomitant hysterectomy impact menopausal symptoms in premenopausal BRCA1/2 pathogenic carriers undergoing risk reducing salpingo-oophorectomy?

Prevention of high-grade serous carcinoma in women with a pathogenic variant in the BRCA1/2 genes includes prophylactic bilateral salpingo-oophorectomy (PBSO). There is debate on whether concomitant hysterectomy should be offered, with benefits including decreased risk of endometrial carcinoma and the option to use estrogen-alone menopausal hormone therapy (MHT), which is thought to be associated with better menopause-specific quality of life and lower breast cancer risk. The objective is to determine if BRCA1/2 mutation carriers undergoing premenopausal PBSO with concomitant hysterectomy have improved MENQOL compared with those women with an intact uterus.

Exploring Survey-Based Water, Sanitation, and Animal Associations With Enteric Pathogen Carriage: Comparing Results in a Cohort of Cases With Moderate-to-Severe Diarrhea to Those in Controls in the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015–2018

The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study. In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged <5 years with moderate-to-severe diarrhea and their matched controls (diarrhea-free in prior 7 days) via the TaqMan Array Card and surveyed caregivers about household drinking water and sanitation conditions and animals living in the compound. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using modified Poisson regression models, stratified for cases and controls and adjusted for age, sex, site, and demographics. Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold <35) in the 4840 cases and 6213 controls. In cases, unimproved sanitation (RR, 1.56; 95% CI, 1.12-2.17), as well as cows (RR, 1.61; 95% CI, 1.16-2.24) and sheep (RR, 1.48; 95% CI, 1.11-1.96) living in the compound, were associated with Shiga toxin-producing Escherichia coli. In controls, fowl (RR, 1.30; 95% CI, 1.15-1.47) were associated with Campylobacter spp. In controls, surface water sources were associated with Cryptosporidium spp., Shigella spp., heat-stable toxin-producing enterotoxigenic E. coli, and Giardia spp. Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children.

The musculoskeletal system diseases in pregnant women with high infection risk and the single nucleotide rs1544410 polymorphism of the calcitriol receptor gene

Background. The problem of vitamin D (VD) deficiency in the population, in general, and in pregnant women, in particular, and related diseases, including the musculoskeletal system, remains one of the most widespread medical and social problems of our time. The purpose was to determine the frequency of musculoskeletal diseases in pregnant females at high infection risk (HIR) with impaired vitamin D status and single-nucleotide Bsml polymorphism of its receptor gene. Materials and methods. Fifty-six pregnant women (main group) with HIR and 40 healthy pregnant women (control group) had been examined. The level of 25-hydroxyvitamin D (25(OH)D) in blood was determined by the enzyme-linked immunosorbent assay, and real-time polymerase chain reaction was used to detect the mutant version of Bsml (rs1544410) polymorphism of the gene that is encoding vitamin D receptors (VDR). Statistical processing of the results was done using the resource www.socscistatistics.com. Results. HIR was due to the presence of chronic kidney diseases, carriers of pathogens of the TORCH group of infections and conditionally pathogenic microflora in the urogenital tract. The level of 25(OH)D was lower than the generally accepted optimal level in 76.8 and 15 % of pregnant women, in the main and control groups, respectively (F = 0.03; p = 0.0001). Carriers of the heterozygous genotype A/G were 67.7 % of pregnant women with HIR compared to 35 % of the control group (odd ratio (OR) = 3.95; 95% confidence interval (CI): 2.19–7.1; χ2 = 20.88, p = 0.00001), and the G/G genotype was inherent in 19.6 and 47.5 % of women, respectively (OR = 0.27; 95% CI 0.15–0.51; p = 0.00006). A third of pregnant women from the main group had a history of musculoskeletal diseases (32.14 %) versus 12.5 % in control group (OR = 3.15; 95% CI: 1.54–6.46); 71.4 % of pregnant women with HIR were carriers of A/G genotype (OR = 9.79; 95% CI: 5.10–18.82). Conclusions. The share of vitamin D deficiency/insufficiency in pregnant women with HIR is almost 77 %. The general somatic history of these women is characterized by a high frequency of the kidney diseases (37.5 %) and musculoskeletal diseases (32.1 %). Two-thirds of pregnant women with HIR, as well as with musculoskeletal diseases, are carriers of the heterozygous Bsml of polymorphic genotype A/G of the VDR gene, which probably causes a higher risk of the development of pathology in conditions of calcitriol deficiency. Studying VD status, the genetic personification of disease risks, and correction of modified factors in time, in particular, VD deficiency is seen as a promising direction for improving perinatal outcomes and the quality of life of pregnant women in general, but further research is required.

Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease

BackgroundDeep brain stimulation (DBS) is a well-established treatment option for select patients with Parkinson’s Disease (PD). However, response to DBS varies, therefore, the ability to predict who will have better outcomes can aid patient selection. Some PD-related monogenic mutations have been reported among factors that influence response to DBS. However, monogenic disease accounts for only a minority of patients with PD. The polygenic risk score (PRS) is an indication of cumulative genetic risk for disease. The PRS in PD has also been correlated with age of onset and symptom progression, but it is unknown whether correlations exist between PRS and DBS response. Here, we performed a pilot study to look for any such correlation.MethodsWe performed a retrospective analysis of 33 PD patients from the NIH PD Clinic and 13 patients from the Parkinson’s Progression Markers Initiative database who had genetic testing and underwent bilateral subthalamic nucleus DBS surgery and clinical follow-up. A PD-specific PRS was calculated for all 46 patients based on the 90 susceptibility variants identified in the latest PD genome-wide association study. We tested associations between PRS and pre- and post-surgery motor and cognitive measures using multiple regression analysis for up to two years after surgery.ResultsChanges in scores on the Beck Depression Inventory (BDI) were not correlated with PRS when derived from all susceptibility variants, however, when removing pathogenic and high-risk carriers from the calculation, higher PRS was significantly associated with greater reduction in BDI score at 3 months and with similar trend 24 months after DBS. PRS was not a significant predictor of Unified Parkinson’s Disease Rating Scale, Dementia Rating Scale, or phenomic and semantic fluency outcomes at 3- and 24-months after DBS surgery.ConclusionsThis exploratory study suggests that PRS may predict degree of improvement in depressive symptoms after DBS, though was not predictive of motor and other cognitive outcomes after DBS. Additionally, PRS may be most relevant in predicting DBS outcomes in patients lacking pathogenic or high-risk PD variants. However, this was a small preliminary study and response to DBS treatment is multifactorial, therefore, more standardized high-powered studies are needed.

MP44-20 MALE-CARRIERS OF GENE MUTATIONS ASSOCIATED WITH INCREASED RISK OF PROSTATE CANCER: RESULTS FROM A SINGLE INSTITUTION GENETIC COUNSELING CONSULTATION

You have accessJournal of UrologyCME1 Apr 2023MP44-20 MALE-CARRIERS OF GENE MUTATIONS ASSOCIATED WITH INCREASED RISK OF PROSTATE CANCER: RESULTS FROM A SINGLE INSTITUTION GENETIC COUNSELING CONSULTATION Estefania Linares-Espinós, Leticia Ruiz-Gimenez, Emilio Rios, Dario Sánchez-Cabrero, Elisa York Pineda, Asier Leibar, Jose María Alonso-Dorrego, and Luis Martínez-Piñeiro Estefania Linares-EspinósEstefania Linares-Espinós More articles by this author , Leticia Ruiz-GimenezLeticia Ruiz-Gimenez More articles by this author , Emilio RiosEmilio Rios More articles by this author , Dario Sánchez-CabreroDario Sánchez-Cabrero More articles by this author , Elisa York PinedaElisa York Pineda More articles by this author , Asier LeibarAsier Leibar More articles by this author , Jose María Alonso-DorregoJose María Alonso-Dorrego More articles by this author , and Luis Martínez-PiñeiroLuis Martínez-Piñeiro More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current international guidelines address genetic counseling for patients with Prostate Cancer (PCa) and family history and/or metastatic PCa (mPCa). We aimed to analyze results from males evaluated at our Family Cancer and Genetic Counseling Unit. METHODS: Between 07-2020 and 09-2022, 1472 patients were counseled for genetic testing, of whom 318 (21,6%) were men. Male patients referred by urologists had at least one criteria of: (a) mutation carrier family member, (b) mPCa, (c) PCa and family history of mPCa, (d) high risk PCa <60y and family history of PCa, and (e) PCa <60y and family history of breast or ovarian cancer at <50y.Identified mutations on tested males were recorded as pathogenic, variants of uncertain significance or negative. We analyzed patient and disease characteristics on pathogenic carriers. We reviewed management recommendations of male healthy carriers. RESULTS: Eighty-nine (28%) males had a pathogenic mutation on genetic testing. Fifthy-Five (17%) were related to PCa genetic counseling. We divided carriers into two groups: Group A (healthy carriers) and Group B (oncologic patients with identified pathogenic mutation). Group A (28/55; 51%) were tested due to known family mutation on close blood relatives. Family history was breast cancer in 24 (86%), PCa in 9 (32%), and HOBC in 6 (21%) HBOC. Median age was 41 (range 15-70), and pathogenic mutations were: 4 ATM, 7 BRCA1, 9 BRCA2, 1 MLH1, 2 MUTHY, 5 RAD51D and 1 TP53. Mean PSA was 1,02ng/dl (range 0,32-3,96). All group A patients had follow-up scheduled in Urology Genetic Counseling clinic and General Surgery Breast and Pancreas Cancer Unit. Healthy carriers had adapted PCa screening. Group B (27/55; 49%) patients had cancer: 16 (59%) had PCa, 7 (26%) Colorectal cancer and 4 (15%) other cancers. Median age was 52 (range 39-80). Family history of PCa was present in 13 (48%). Germline pathogenic mutations were found in 25 (93%): 4 ATM, 5 BRCA1, 4 BRCA2, 1 HOXB13, 2 MLH1, 1 MSH2, 1 MUTYH, 3 PALB2, 1 PMS2, 2 RAD51D and 2 TP53. Two patients (7%) had somatic pathogenic mutations. Out of the 16 patients with PCa, 37,5% had mPCa, 31,3% high risk PCa and 31,3% had intermediate risk PCa diagnosed at age <50y and >2 relatives with PCa. Somatic mutations were identified on mPCa. CONCLUSIONS: We found 28% of positive genetic testing in males.Patients with identified pathogenic variants should be recommended close follow-up as some are associated with aggressive PCa.The widespread use of genetic testing in other malignancies (i.e. Breast Cancer, HOBC), will increase healthy carriers. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e620 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Estefania Linares-Espinós More articles by this author Leticia Ruiz-Gimenez More articles by this author Emilio Rios More articles by this author Dario Sánchez-Cabrero More articles by this author Elisa York Pineda More articles by this author Asier Leibar More articles by this author Jose María Alonso-Dorrego More articles by this author Luis Martínez-Piñeiro More articles by this author Expand All Advertisement PDF downloadLoading ...