Sporadic Cases Research Articles

Overexpression of autophagy enhancer PACER/RUBCNL in neurons accelerates disease in the SOD1G93A ALS mouse model

AbstractAmyotrophic lateral sclerosis (ALS) is a debilitating and fatal paralytic disorder associated with motor neuron death. Mutant superoxide dismutase 1 (SOD1) misfolding and aggregation have been linked to familial ALS, with the accumulation of abnormal wild-type SOD1 species being also observed in postmortem tissue of sporadic ALS cases. Both wild-type and mutated SOD1 are reported to contribute to motoneuron cell death. The autophagic pathway has been shown to be dysregulated in ALS. Recent evidence suggests a dual time-dependent role of autophagy in the progression of the disease. PACER, also called RUBCNL (Rubicon-like), is an enhancer of autophagy and has been found diminished in its levels during ALS pathology in mice and humans. Pacer loss of function disturbs the autophagy process and leads to the accumulation of SOD1 aggregates, as well as sensitizes neurons to death. Therefore, here we investigated if constitutive overexpression of PACER in neurons since early development is beneficial in an in vivo model of ALS. We generated a transgenic mouse model overexpressing human PACER in neurons, which then was crossbred with the mutant SOD1G93A ALS mouse model. Unexpectedly, PACER/SOD1G93A double transgenic mice exhibited an earlier disease onset and shorter lifespan than did littermate SOD1G93A mice. The overexpression of PACER in neurons in vivo and in vitro increased the accumulation of SOD1 aggregates, possibly due to impaired autophagy. These results suggest that similar to Pacer loss-of function, Pacer gain-of function is detrimental to autophagy, increases SOD1 aggregation and worsens ALS pathogenesis. In a wider context, our results indicate the requirement to maintain a fine balance of PACER protein levels to sustain proteostasis.

Tężec w Polsce w latach 2020-2022

BackgroundTetanus is an infectious disease caused by the bacterium <i>Clostridium tetani,</i> which produces a neurotoxin (tetanospasmin) that causes spastic paralysis. This disease can only be prevented by vaccination. Tetanus is very rare in EU countries, where it mainly affects people over 60 years of age. Tetanus is a serious health problem in countries with low vaccination rates and poor hygiene conditions, and neonatal tetanus is a particularly significant problem in these countries. In Poland, according to the Vaccination Program, mandatory vaccinations against tetanus should be given to children and adolescents up to the age of 19.ObjectiveThe aim of the study was to assess the epidemiological situation of tetanus in Poland in 2020-2022.Material and methodsThe assessment of the epidemiological situation of tetanus in Poland in 2020-2022 was made based on the interpretation of data from the annual bulletins "Infectious diseases and poisonings in Poland" for 2020-2022 and the bulletins "Vaccinations in Poland" for 2020-2022 as well as data from individual epidemiological reports on diseases registered in the "Epibaza" system.ResultsIn 2020, 2 cases of tetanus were registered in Poland, in 2021 – 5 cases, and in 2022 also 5 cases. The total incidence in 2020 was 0.005 per 100 000 people, in 2021 and 2022 – 0.013 per 100 000 and was lower compared to the median for 2015-2019 (0.031). In 2020-2021, all reports concerned hospitalized people, while in 2022 one person was treated as an outpatient. No cases were recorded in people under 30 years of age.ConclusionsIn Poland, a decrease in the number of reported tetanus cases was observed in 2020-2022 compared to previous years. Sporadic tetanus cases in Poland are recorded mainly in older age groups but also occur among adults under 60 years of age. The cases can be associated with the lack of booster vaccinations in adults.

Recent Molecular Epidemiology of Echovirus 11 Throughout North and West Africa Resulted in the First Identification of a Recombinant Strain from an Acute Flaccid Paralysis Case in West Africa

Echovirus 11 has emerged as a major public health concern, causing sepsis in neonates in many European countries in recent years. In Africa, especially West Africa, where resources and diagnostic capacities are limited, only sporadic cases have been reported. To better understand the recent molecular epidemiology of E11 in West Africa, we characterized twenty-three echovirus 11 strains isolated through the acute flaccid paralysis and environmental surveillance systems for polio from 2013 to 2023, using high-throughput sequencing. Our data are noteworthy due to identifying for the first time a recombinant strain from an acute flaccid paralysis case and represent the first focus to date on molecular characterization of echovirus 11 in West Africa. Moreover, our data show that echovirus 11 diverged from 1970 (95% HPD range, 1961–1979) and evolved into four distinct clades, with the virus spread from West Africa to Europe, exhibiting two introductions in France around 2017, from Senegal and Guinea. Furthermore, the in silico analysis reveals four non-conservative amino acid substitutions in the VP1 sequences of the European strains associated with neonatal sepsis in newborns and a conserved amino acid motif in the VP1 protein toward enterovirus genotypes. Our data provide new insights into the epidemiology of echovirus 11 and point to the crucial need to implement specific surveillance programs targeting non-polio enteroviruses for the rapid identification of emerging or re-emerging enterovirus species, particularly in Africa.

Molecular epidemiology and pathogenicity of Wesselsbron virus circulating in Africa.

Wesselsbron is a neglected, mosquito-borne zoonotic disease transmitted by several species of virus-infected Aedes mosquitoes endemic to tropical regions in Africa. It affects primarily domestic livestock species with teratogenic effects, but can jump to humans. Herein, we investigated the molecular epidemiology of Wesselsbron virus in Africa using whole genome sequencing and structural analysis, and assessed its pathogenicity and tropism through in vivo experiments. A total of twenty-five isolates collected from three countries were successfully characterized. Our study is noteworthy by identifying, for the first time, inter-clade recombination events on the genome of Wesselsbron virus. However, more investigations on the precise molecular mechanisms conducting the occurrence of recombination on the genome of Wesselsbron virus, are warranted. The identification of polymorphisms on motifs of virulence and selection pressures on major proteins showed evidence of genetic evolution for Wesselsbron virus. The clade 1 was more pathogenic and neurotropic in suckling mice and the intramuscular route was found to be the best transmission mode. Our findings also provide new insights in the pathogenicity and tropism of Wesselsbron virus, which could be useful for prevention, preparedness and future outbreak response. Considering its high prevalence in mosquito populations and the increasing number of sporadic human cases, Wesselsbron virus merits more attention in terms of prevention and preparedness, as its mosquito vectors continue to globally expand and there is no vaccine.

A novel ATP2A2 mutation in Darier and genotype phenotype: correlation analysis.

Darier's disease (DD) is a skin disorder caused by mutations in the ATP2A2 gene. Researchers have been investigating the correlation between genotype and phenotype in DD. Understanding the genotype-phenotype relationship in DD can enhance our comprehension of the genetic background and phenotypic characteristics of the condition, as well as the relationship between its systemic and localized manifestations. This study aimed to investigate the molecular pathogenesis of DD in a Chinese family, and to elucidate the genotype-phenotype correlation in DD by summarizing relevant literature. Gene mutations associated with DD were screened by whole-exome sequencing and verified using Sanger sequencing. Genetic analysis assessed the potential impact of these mutations. Genotype-phenotype correlation was obtained by chi-square analysis using literature search test. (1) A novel ATP2A2 Missense mutation, c.2560T>C (p.W854R), was identified and confirmed by Sanger sequencing. Annotation analysis with the ANNOVAR tool indicated that this mutation disrupts normal protein function and is linked to DD clinical manifestations. (2) Genotype-phenotype analysis showed a significant correlation between the prevalence of DD-related mental disorders and geographic regions (P = 0.00), but no association between mutation type and mental disorder prevalence (P = 0.324). The age of onset varied between sporadic and familial cases (P = 0.032), averaging 33years in sporadic cases and 16years in familial cases. By analyzing the genotype-phenotype correlation, we aim to enhance our understanding of the genetic basis of DD. This research could improve early diagnosis, intervention, and the development of personalized long-term health management plans.

Small fiber neuropathy associated with COVID-19 infection and vaccination: A prospective case-control study.

Small fiber neuropathy (SFN) after both COVID-19 infection or vaccination has been reported in sporadic cases, but a detailed description and comparison are missing. We aimed to screen a large cohort of patients complaining of pain and autonomic symptoms after COVID-19 natural infection or vaccination to ascertain the presence of SFN and its correlation with autoimmune diseases. We prospectively recruited for this case-control study 66 patients: 33 developing sensory and autonomic symptoms after a natural COVID-19 infection (P-COVID) and 33 after a mRNA vaccination against COVID-19 (P-VAC). We also used 33 matched healthy controls (HC) collected before 2019 when the COVID-19 virus appeared. Patients underwent neurological examination and clinical scales, an extensive serum screening, and skin biopsy to detect small nerve fiber involvement. Clinical scales showed higher scores for autonomic symptoms in P-COVID patients than in P-VAC patients, but the other scales did not differ. P-COVID and P-VAC patients showed a significant decrease in somatic small nerve fibers compared with HC, whereas autonomic innervation did not differ. SFN was more frequent in P-COVID patients (94%) than in P-VAC patients (79%). Epidermal innervation was correlated with clinical scales for pain and autonomic dysfunctions. Autoimmune abnormalities were frequent in both groups but importantly they were not correlated with SFN. Somatic SFN was frequently found in both P-COVID and P-VAC patients, with a higher incidence in the former group. Spared skin autonomic innervation was spared in both groups although a subtle autonomic involvement in P-COVID patients was suggested by a high COMPASS-31 scale score. SFN was not correlated with autoimmune dysfunctions, although autoimmune diseases were frequent in both groups.

Rhegmatogenous Retinal Detachment Secondary to Type I Stickler Syndrome: Diagnosis, Treatment and Long-Term Outcomes

Objective: This study aimed to clarify the genetic diagnosis of rhegmatogenous retinal detachment (RRD) secondary to type I Stickler syndrome (STL1) and evaluate the anatomical and functional outcomes of surgical treatment. Methods: This retrospective study included 11 patients with RRD secondary to STL1. Familial and sporadic cases of STL1 were diagnosed at the Eye & ENT Hospital, Fudan University, between 2017 and 2023. To clarify the genetic diagnosis, next-generation sequencing was performed in suspected STL1 cases. Further, standard ocular examinations and surgical treatment were performed. Results: Nine variants of COL2A1, including four novel mutations (c.394G>T, c.2977G>T, c.3003+2dup, and c.3853G>C), were screened and identified. The pathogenicity of all variants was conclusively demonstrated. Among patients who underwent vitrectomy, the mean age at RRD was 11.5 years, and the mean follow-up was 32.9 months. The average number of surgical procedures required during the follow-up was two; 90.9% of eyes achieved final attachment, and best corrected visual acuity (BCVA) significantly improved in 81.8% of the eyes, with a middle postoperative logMAR BCVA of 0.52 compared with the preoperative value (p = 0.0148). High intraocular pressure (81.8%) and cataract (72.7%) were the most common complications. Conclusions: Our study expands the spectrum of COL2A1 mutations and provides a novel diagnostic strategy for STL1. By combining clinical manifestations with genetic testing, STL1 could be accurately diagnosed. With proper surgical treatment and long-term follow-up, the prognosis of RRD in patients with STL1 could be improved.

Emergence of Streptococcus suis infection from Goa, India

Abstract Streptococcus suis is an emerging zoonotic bacterium that causes severe invasive disease in humans. In India, only two human case reports have been recorded till now. In the present report, we described the clinical case report along with an epidemiological investigation of the first S. suis case from Goa, India. The clinical presentation and detailed history regarding the potential exposure factors for the infection were recorded and to trace the source of the infection, the meat markets and the backyard piggeries in the vicinity of the patient’s residence were investigated. Case definitions were formulated and enhanced surveillance was initiated in the State to identify any additional cases. The case-patient was a co-morbid 63-year-old female, who was provisionally diagnosed with meningitis and septicaemia and S . suis infection was detected using automated microbial identification systems. The epidemiological investigation revealed that the patient was involved in handling raw pork one day prior to the symptom onset. Based on the active case finding, no additional case of S. suis was detected in the area. The present case was a sporadic case of S. suis in Goa, India and case-patient may have been exposed to the bacteria by handling raw pork while cooking. One Health impact statement Our investigation described the 3rd case of Streptococcous suis from India. This is significant because despite the abundance of the source of infection across the country i.e. high prevalence in the pig population, there are unusually low number of human cases, which can be attributed to very low clinical index of suspicion and lack of diagnostic tests in humans, as evidenced in the present case. A multi-disciplinary One Health approach has been applied for the present case investigation as the Human Health, Animal Health and Food Safety aspects were investigated in collaboration with the State Health & Animal Husbandry departments along with the academia. The findings of the present investigation will aid in enhancing the clinical index of suspicion among clinicians and awareness among high-risk groups like veterinarians for S. suis infection in humans and animals. The multi-disciplinary One Health approach aided us in tracing the source of the infection, which would help in generating evidence for designing preventive interventions.

Neonatal Presentation of Severe Hemophilia A: An Original Case Report and a Literature Review

Introduction: We report the case of a neonate diagnosed with severe hemophilia A (HA) and conduct a literature review of cases of severe HA presenting at the neonatal age to help define the clinical diagnostic findings and existing differences between the sporadic and familial onset of this condition. Report of a Case: A 6-day-old newborn presented with worsening pallor, inappetence, and hyporeactivity for 48 h. The diagnosis was severe hemophilia A (HA), leading to an unfavorable outcome. A literature review focusing on case reports and series focusing on the clinical expression of HA in neonates was conducted, documenting clinical presentation, family history, and outcomes. Literature review: Forty patients were included. HA was observed in five cases (12.5%) of very preterm births (≤32 weeks) and in four cases (10%) of moderately or late preterm births. Seventeen patients (43%) had a family history, with inheritance being sporadic (21 newborns, 53%) or acquired (2 cases, 4%). Clinical onset typically occurred within the first week of life (approximately 8 out of 10 cases), while only three cases (7.5%) had onset after the first month. Inherited cases presented with hemorrhagic states (nine cases), hypovolemic shock (five cases), or intracranial hypertension (two cases). Sporadic cases showed localized bleeding (11 cases), hypovolemic shock (5 cases), or neurological symptoms like seizures and anisocoria (5 cases). Acquired cases included severe intracranial hemorrhage in one case. Conclusions: Neonatal HA can manifest with severe symptoms and rapid progression, making early diagnosis crucial. Non-specific signs and the absence of coagulophaty disorders in family history can delay diagnosis. Symptoms like prolonged bleeding, cutaneous hematomas, or intracranial bleeding necessitate ruling out major coagulopathy, and neurological signs require immediate imaging to exclude intracranial bleeding.

Genomic perspectives on foodborne illness

Whole-genome sequencing of bacterial pathogens is used by public health agencies to link cases of food poisoning caused by the same source of contamination. The vast majority of these appear to be sporadic cases associated with small contamination episodes and do not trigger investigations. A "contamination episode" refers to one or more contamination events from a single source over a period of time. We examine clusters of sequenced clinical isolates of Salmonella, Escherichia coli, Campylobacter, and Listeria that differ by only a small number of mutations (SNPs) to identify features of the underlying contamination episodes. These analyses provide additional evidence that the youngest age groups have greater susceptibility to infection by Salmonella, E. coli, and Campylobacter than older age groups. This age bias is weaker for the common Salmonella serovar Enteritidis than Salmonella in general. A large fraction of the contamination episodes causing sickness appear to have a long duration. For example, 50% of the Salmonella cases are in clusters that persist for almost 3 y. For all four pathogen species, the majority of the cases were part of genetic clusters with illnesses in multiple states and likely to be caused by contaminated commercially distributed foods. Salmonella infections in infants under 3 mo are predominantly acquired from the same contaminated food, pet food, or environmental sources as older individuals, rather than infant formula contaminated during production.

Coxiella burnetii caused lumbar infection: A case report and literature review

Coxiella burnetii (C. burnetii)is a significant microbe linked to the zoonotic disease Q fever, known for its atypical clinical manifestations and sporadic cases. It can cause lumbar infections. In this report, we present a 66-year-old male sheep farmer who experienced low back pain for five months, with worsening numbness in both lower limbs over two months. Several standard diagnostic tests were negative. Metagenomic next-generation sequencing (mNGS) was performed on lumbar spine tissue obtained via biopsy, identifying C. burnetii infection. After surgical excision of the lesion, the patient received a combination of levofloxacin, doxycycline, rifampicin, and supportive medications. Postoperatively, the patient's condition stabilized, showing a significant reduction in low back pain. This case highlights mNGS as a valuable tool for diagnosing rare infections, especially in patients with a history of animal exposure. It underscores the importance of considering zoonotic infections and the need for combined antibiotic and surgical management in suspected cases.

Analysis of epidemiological and clinical manifestations of foodborne botulism in the Volgograd region

Aim. To analyze the situation regarding manifestations of foodborne botulism in the Volgograd region in the 2005–2023 period.Materials and methods. A retrospective analysis of 158 records of hospital patients with a diagnosis of foodborne botulism was carried out. The epidemiological data under analysis included transmission factors and outcomes. The clinical data under analysis were duration of the incubation period, severity of clinical manifestations at the time of admission and during the course of the disease, severity of changes in laboratory parameters, studies of biological material for the presence of botulinum toxin. Statistical data were processed using the MS Excel and Stastica 10.0 MS Office software packages. Results. Predominant sporadic cases of botulism were identified. The leading factors of infection transmission and the predominant type of botulinum toxin in the Volgograd region in the period from 2005 to 2023 were determined.Conclusion. Physicians and other specialists working in outpatient facilities and hospital emergency departments should maintain updated knowledge about this severe food bacterial poisoning.

Comparative analysis of stereotactic radiosurgery outcomes for supratentorial hemangioblastomas in von hippel-lindau disease and sporadic cases: A multi-center international study

BackgroundHemangioblastomas (HBs) are rare, benign central nervous system (CNS) neoplasms that rarely occur in the supratentorial. Resection with the goal of gross total resection (GTR) is often considered the primary treatment. Stereotactic radiosurgery (SRS) has been utilized more commonly in unresectable or partially resected cases. In this study, we aimed to evaluate SRS’s effectiveness and clinical outcomes in supratentorial HBs. MethodsA retrospective analysis of multi-centers from 1993 to 2022 was conducted on patients with supratentorial HB treated with SRS. ResultsThe study included 13 patients with 30 supratentorial HBs (24 von Hippel-Lindau (VHL), 6 sporadic). Median age was 26 years. Most tumors were solid (86.2 %). SRS was primary treatment in 86.7 % of cases and adjuvant in 13.3 %. VHL lesions were significantly smaller than sporadic ones (0.2 vs. 3.7 cc, p = 0.009). Median margin dose was higher in VHL cases (17 vs. 13.0 Gy, P = 0.031). For VHL cases, local control (LC) was 100 % at 6 months, 96 % (95 % CI: 88 %, 100 %) from 12 to 60 months post-SRS. For sporadic cases, LC was 100 % at 6 months, 80 % (95 % CI: 52 %, 100 %) from 12 to 60 months post-SRS (p = 0.39). No adverse radiation events or mortality occurred. ConclusionSRS demonstrated a promising role in the clinical course of supratentorial HBs. It can be considered an effective alternative to surgical resection and even a first-line therapeutic option in appropriately selected cases.

Seven-year overview of antimicrobial resistance in diarrheagenic Escherichia coli from sporadic human diarrhea cases in 20 Chinese provinces

Diarrheagenic Escherichia coli is one of the most prevalent foodborne pathogens and poses significant clinical challenges due to increasing rates of antibiotic resistance. In this study, 9,068 diarrheagenic E. coli isolates from sporadic diarrhea cases across 20 provinces of China from 2016 to 2022 were systematically analyzed to determine the prevalence and distribution of resistance. A total of 14 antibiotics were included in the antimicrobial resistance surveillance. Antimicrobial susceptibility testing indicated that the majority of the isolates (89.3%) were resistant to at least one antimicrobial agent, with a significant proportion (60.3%) demonstrating multidrug resistance. Isolates showed high levels of resistance to ampicillin (68.2%) and high sensitivity to imipenem (97.0%). Over the 7 years, an increasing trend in resistance to cefoxitin and chloramphenicol among the isolates was found. Enteroaggregative E. coli was identified as the predominant pathotype. Furthermore, antimicrobial resistance rates were higher among the isolates from infants under 1 year of age compared to other populations and resistance levels differed among pathotypes. In summary, our findings revealed the detailed resistance characteristics of diarrheagenic E. coli strains isolated from human sporadic diarrhea cases in China, offering valuable insights that can inform clinical antibiotic treatment strategies and priorities.

Enteric Adenovirus Gastroenteritis in Under-Five Children, Kano-Nigeria

Abstract Context: Adenoviruses have been implicated in many outbreaks and sporadic cases of pediatric gastroenteritis. Aim: This study aimed to determine the prevalence and circulating serotype(s) of enteric adenoviruses among under-five children with diarrheal diseases in Kano, Nigeria. Settings and Designs: This was a multicentered hospital-based cross-sectional study involving 250 under-five children recruited from Murtala Muhammad Specialist Hospital, Muhammad Abdullahi Wase Teaching Hospital and Hasiya Bayero Paediatric Hospital. Materials and Methods: Enteric adenovirus F40/F41 were checked in the stools of children exhibiting symptoms of gastroenteritis, diarrhea, and/or vomiting by nested PCR amplification of the adenovirus Hexa/E1B regions and positive samples characterized by sequencing and phylogenetic analysis. Statistical Analysis Used: Data generated were analyzed using descriptive statistics, and the association between the variables was checked by the Chi-square test. A P value <0.05 was considered statistically significant. Results: The nested PCR result shows that 7 (2.8%) out of the 250 stools were positive for enteric adenovirus (group F), with only serotype F41 detected within the cohort examined. The isolates were more closely related to KJ425126 from Gabon. The results highlighted that fever and vomiting are prominent features of adenovirus F41 gastroenteritis and children 1–2 years especially males were mostly affected. Conclusion: The study improved our knowledge and understanding of the role of enteric adenovirus in under-five gastroenteritis and suggests that EAdeV-F41 is an important cause of gastrointestinal infections, particularly in infants and young children in Kano, Nigeria. This may call for routine screening of the stools of children with diarrhea for future management guidelines.

Juvenile Spring Eruption: A Report on an Outbreak and 2 Sporadic Cases in French Military Personnel.

Juvenile spring eruption is a sun-related skin eruption primarily affecting boys or young adult males. The pathophysiology is unknown, but there appears to be a link with sun exposure in cold weather. It can cause small outbreaks, particularly in groups of children or young adults. The primary lesions can be pruritic erythema, with or without associated papules, vesicles, or bullae. They are notable for almost exclusively affecting the ears. Spontaneous healing occurs within a few days without leaving scars. We report an outbreak and 2 sporadic cases that occurred at the Valdahon military camp in France between 2021 and 2024 among military personnel.

Expanded geographic distribution for two Legionella pneumophila sequence types of clinical concern.

Legionella pneumophila serogroup 1 sequence types (ST) 213 and 222, a single-locus variant of ST213, were first detected in the early 1990s in the Midwest United States (U.S.) and the late 1990s in the Northeast U.S. and Canada. Since 1992, these STs have increasingly been implicated in community-acquired sporadic and outbreak-associated Legionnaires' disease (LD) cases. We were interested in understanding the change in LD frequency due to these STs and identifying genetic features that differentiate these STs from one another. For the geographic area examined here (Mountain West to Northeast) and over the study period (1992-2020), ST213/222-associated LD cases identified by the Centers for Disease Control and Prevention increased by 0.15 cases per year, with ST213/222-associated LD cases concentrated in four states: Michigan (26%), New York (18%), Minnesota (16%), and Ohio (10%). Additionally, between 2002 and 2021, ST222 caused at least five LD outbreaks in the U.S.; no known outbreaks due to ST213 occurred in the U.S. during this time. We compared the genomes of 230 ST213/222 isolates and found that the mean of the average nucleotide identity (ANI) within each ST was high (99.92% for ST222 and 99.92% for ST213), with a minimum between ST ANI of 99.50% and a maximum of 99.87%, indicating low genetic diversity within and between these STs. While genomic features were identified (e.g., plasmids and CRISPR-Cas systems), no association explained the increasing geographic distribution and prevalence of ST213 and ST222. Yet, we provide evidence of the expanded geographical distribution of ST213 and ST222 in the U.S.IMPORTANCESince the 1990s, cases of Legionnaires' disease (LD) attributed to a pair of closely related Legionella pneumophila variants, ST213 and ST222, have increased in the U.S. Furthermore, between 2002 and 2021, ST222 caused at least five outbreaks of LD in the U.S., while ST213 has not been linked to any U.S. outbreak. We wanted to understand how the rate of LD cases attributed to these variants has changed over time and compare the genetic features of the two variants. Between 1992 and 2020, we determined an increase of 0.15 LD cases ascribed to ST213/222 per year in the geographic region studied. Our research shows that these STs are spreading within the U.S., yet most of the cases occurred in four states: Michigan, New York, Minnesota, and Ohio. Additionally, we found little genetic diversity within and between these STs nor could specific genetic features explain their geographic spread.

Investigating Transmission Patterns and Genome Sequencing of SARS-CoV-2 in University College Dublin

Abstract Background This study describes the investigation and management of multiple outbreaks of SARS-Cov2 during the second and third wave of the pandemic at University College Dublin, Ireland from September 2020 to September 2021. Methods Relevant data were gathered as part of the public health outbreak investigations led by the UCD Internal Covid Control Team (ICCT) in collaboration with the public health teams of the Health Service Executive (HSE). Results are presented for PCR (polymerase chain reaction) confirmed cases and their close contacts, reported to the UCD ICCT between September 2020 to September 2021. Results There were 214 cases notified to ICCT. Among these, 153 cases were in residence on-campus cases. 73 epidemiologically linked clusters identified, where the number of cases linked with each cluster varied between 1 to 27. Additional cases during this period had no obvious epidemiological link to the identified clusters. Of 902 close contacts with PCR test results, 31.5% (n = 284) tested positive. 77% (n = 219) self-reported with mild to moderately symptoms while 23% (n = 65) self-reported as asymptomatic. Retrospective Whole Genome Sequence (WGS) analysis was undertaken after the outbreaks had subsided. The test positive cases were grouped into 6 clusters, and it was shown that many of the apparent sporadic cases were included in these clusters. Conclusions The proportion of close contacts testing positive varied significantly throughout the pandemic, with testing policy and type of exposure having the greatest impact. Whole genome sequencing can give a better understanding of webs of transmission to complement epidemiological investigations. It is now possible to undertake sequencing in real time where it can make a contribution to outbreak control and resolution. Public Health professionals should become familiar with WGS and bioinformatics as useful tools in their armory for the control of all communicable diseases not only SARS-CoV-2. Key messages • Combined epidemiological investigations and Whole Genome Sequencing (WGS) provide crucial insights into campus COVID-19 outbreaks, guiding effective control measures. • WGS integration enhances understanding of transmission patterns, identifies clusters, and equips public health professionals with data-driven approaches for outbreak management beyond SARS-CoV-2.

Satisfactory Clinical Response to Erlotinib in a Patient Diagnosed with Olmsted Syndrome.

Olmsted syndrome is a rare congenital keratinization disorder characterized by mutilating palmoplantar keratoderma (PPK), often accompanied by flexion deformity, periorificial keratotic plaques, and hair abnormalities. The majority of Olmsted syndrome cases are attributed to mutations in the TRPV3 (Transient receptor potential vanillin 3) gene(1). Herein, we aim to present a sporadic case of Olmsted syndrome with a recurrent c1717G>T p.Gly573Cys variant in the TRPV3 gene, demonstrating clinical improvement with the epidermal growth factor inhibitor Erlotinib.

Two Sporadic Cases of Legionellosis Associated with the Use of Domestic Ultrasonic Humidifiers

Two sporadic cases of legionellosis occurring in consecutive years were confirmed by positive antigenuria to Legionella pneumophila serogroup 1 in individuals with limited mobility who were confined to their homes. Both cases had a history of using ultrasonic humidifiers and of low exposure to other possible sources of infection. This study was conducted through an expanded epidemiological survey and home inspection. Samples were collected from domestic hot water and humidifiers. Environmental isolates were characterised by immunoagglutination and immunofluorescence. The Dresden panel is employed for the determination of groups and subgroups of serogroup 1. The amoebae were isolated by water filtration and subsequent cultivation of the filters. Identification of the isolates was conducted through the sequencing of PCR products. In both cases, epidemiological studies identified the ultrasonic humidifiers as the probable source of infection. The presence of Legionella pneumophila was confirmed in the sanitary water installation and in the humidifiers, where high values of Legionella pneumophila serogroup 1 counts were also obtained. The isolates were characterised as Olda Oxford and Olda OLDA. Furthermore, in addition to the Legionella isolates, the presence of Vermamoeba vermiformis was also identified in samples obtained from domestic hot water and humidifiers in one of the residential addresses under investigation. It has been demonstrated that humidifiers can act as an amplification mechanism for pathogenic microorganisms when they are not cleaned and maintained correctly. This can pose a health danger, especially to people with previous respiratory pathologies, the immunosuppressed, and the elderly. Therefore, it is of the utmost importance that professionals who recommend the therapeutic use of this equipment should issue warnings regarding the importance of its correct use, cleaning, and disinfection. Finally, humidifiers should be considered in epidemiological surveys and in the study of sporadic cases.