Unidentified Pathogen Research Articles

Recent Outbreaks and Factsheet of Future Global Pandemic Marburg Virus: A Looming Threat

Abstract: The Marburg virus (MARV), which belongs to the family Filoviridae, is the cause of Marburg virus disease (MVD), a disease that can be fatal. Laboratories employees of Marburg and Frankfurt cities of Germany, and Belgrade city of Yugoslavia (now Serbia), contracted an infection caused by a hitherto unidentified infectious pathogen in August 1967. According to the World Health Organization (WHO), MARV is one of the most im-portant issues in the world. With a case fatality rate ranging from 24.0 to 88.0%, the virus is very dangerous, underscoring the need for public awareness. This outbreak was deter-mined to be caused by the MARV, one of the deadliest viruses that infect humans. However, African green monkeys (Chlorocebus aethiops), which were imported from Uganda and transported to all three locations, were discovered to be the virus's primary source, while fruit bats (Rosettus aegyptiacus), which belong to the Pteropodidae family, act as the MARV's natural hosts. The disease's pathophysiology indicates significant antiviral suppression as a result of alter-ations in gene expression and the synthesis of interferon-stimulated genes in the hepatic cells. Along with the advent of hemorrhagic manifestations, which can result in a patient's death, the condition may worsen and cause abdominal discomfort, nausea, vomiting, phar-yngitis, diarrhea, and other symptoms. The countermeasures against MVD are outlined in this article, with an emphasis on the ecology, traits, virion proteins, pathology, and trans-mission of MARV clinical aspects along with diagnostic, patient therapy, and management.

Global Case Fatality of Bacterial Meningitis During an 80-Year Period

The impact of vaccination, antibiotics, and anti-inflammatory treatment on pathogen distribution and outcome of bacterial meningitis over the past century is uncertain. To describe worldwide pathogen distribution and case fatality ratios of community-acquired bacterial meningitis. Google Scholar and MEDLINE were searched in January 2022 using the search terms bacterial meningitis and mortality. Included studies reported at least 10 patients with bacterial meningitis and survival status. Studies that selected participants by a specific risk factor, had a mean observation period before 1940, or had more than 10% of patients with health care-associated meningitis, tuberculous meningitis, or missing outcome were excluded. Data were extracted by 1 author and verified by a second author. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Random-effects models stratified by age (ie, neonates, children, adults), Human Development Index (ie, low-income or high-income countries), and decade and meta-regression using the study period's year as an estimator variable were used. Case fatality ratios of bacterial meningitis. This review included 371 studies performed in 108 countries from January 1, 1935, to December 31, 2019, describing 157 656 episodes. Of the 33 295 episodes for which the patients' sex was reported, 13 452 (40%) occurred in females. Causative pathogens were reported in 104 598 episodes with Neisseria meningitidis in 26 344 (25%) episodes, Streptococcus pneumoniae in 26 035 (25%) episodes, Haemophilus influenzae in 22 722 (22%), other bacteria in 19 161 (18%) episodes, and unidentified pathogen in 10 336 (10%) episodes. The overall case fatality ratio was 18% (95% CI, 16%-19%), decreasing from 32% (95% CI, 24%-40%) before 1961 to 15% (95% CI, 12%-19%) after 2010. It was highest in meningitis caused by Listeria monocytogenes at 27% (95% CI, 24%-31%) and pneumococci at 24% (95% CI, 22%-26%), compared with meningitis caused by meningococci at 9% (95% CI, 8%-10%) or H influenzae at 11% (95% CI, 10%-13%). Meta-regression showed decreasing case fatality ratios overall and stratified by S pneumoniae, Escherichia coli, or Streptococcus agalactiae (P < .001). In this meta-analysis with meta-regression, declining case fatality ratios of community-acquired bacterial meningitis throughout the last century were observed, but a high burden of disease remained.

Antimicrobial Treatment Challenges in the Management of Infective Spondylodiscitis Associated with Hemodialysis: A Comprehensive Review of Literature and Case Series Analysis.

Infective spondylodiscitis (ISD), the infection of vertebral bodies and surrounding tissues, is a rare complication with major impact on the long-term survival of hemodialysis (HD) patients. Although the most frequent etiology is staphylococcal, identifying these pathogens in blood cultures and biopsy cultures is often difficult. This paper aims to present suitable antibiotic combinations for the treatment of these patients, which is usually challenging in the case of an unidentified pathogen. We presented the therapies applied for 13 HD patients and 19 patients without chronic kidney disease (CKD), diagnosed with ISD between 2013 and 2023 in Bihor County. The percentage of positive blood cultures was low in both groups (30.78% HD vs. 15.78% non-HD). The average length of antibiotic therapy was 5.15 weeks in HD patients and 6.29 weeks in non-HD patients. The use of Carbapenem alone (e.g., Meropenem) for an average of 19.6 days for patients in HD when the pathogen was not identified has proven to be efficient in most cases, similarly to using Vancomycin and Fluoroquinolone/Cephalosporines in combination. Regarding the non-CKD patients, the use of Clindamycin in various combinations for an average of 30.3 days has proven to be efficient in more than 90% of cases of ISD with a nonidentified pathogen. Within 2 years after ISD was diagnosed, 12 of the 13 HD patients passed away, mainly due to cardiovascular causes. Unfortunately, there are no guidelines in the literature concerning the empiric treatment of ISD in the particular case of HD patients. Upon checking the literature on PubMed and Google Scholar, only 10 studies provided relevant data regarding ISD treatment for HD patients. More data about the treatment and evolution of these patients is needed in order to elaborate a truly relevant metanalysis.

Investigation of Agricultural Diseases and Pests in the Republic of Kiribati and the Republic of Fiji

The Republic of Kiribati (Kiribati) and the Republic of Fiji (Fiji) are two island countries in the Middle and Eastern Pacific Ocean, respectively. Coconut (Cocos nucifera L.), banana (Musa spp.), sugarcane (Saccharum officinarum L.), and breadfruit (Artocarpus incisa (Thunb.) L.) are the primary economic crops. To date, there have been few reports on the status of agricultural diseases and pests in these countries. From June 6 to June 16, 2023, our team investigated agricultural diseases and pests in Kiribati and Fiji. Thirty-six diseases, five pests and one parasitic plant from twenty-eight species of plants were identified in Kiribati. Among the deleterious organisms, coconut gray spot (Pestalotiopsis palmarum (Cooke) Steyaert), banana Cordana leaf spot (Cordana musae (Zimm) Hhon), hala (pandanus) leaf blight (Unidentified pathogen), breadfruit anthracnose (Colletotrichum spp.), frangipani rust (Coleosporium plumierae Pat.) and noni anthracnose (Colletotrichum spp.) were predominant. A total of twenty-seven diseases and one parasitic plant were identified on twenty-one species of plants in Fiji. Mango bacterial black spot (Xanthomonas campestris pv. mangiferaeindicae), banana black leaf streak (Pseudocercospora musae (Zimm.) Deighton), pumpkin virus disease (Unidentified), and frangipani rust (Coleosporium plumierae Pat.) were prevalent. The results of our survey could provide the governments of Kiribati and Fiji with basic data to control the primary agricultural diseases and pests in their countries.

Disease X: A Global Threat in the Making

In this letter to the editor, concerns about Disease X have been discussed, highlighting the need for preparedness measures. Disease X represents an unidentified pathogen that could lead to a future epidemic or pandemic, emphasizing the unpredictability of emerging infectious diseases. This letter underscores the importance of proactive surveillance, research, and international collaboration to address potential threats posed by Disease X and other unknown pathogens.

Characteristics, risk factors and outcomes of patients managed for left-sided infective endocarditis: a prospective study in a high-volume center

Abstract Background Although medical and surgical management of infective endocarditis (IE) have improved in the recent decades, the associated mortality remains high. Available prospective data are scarce, and further knowledge from prospective cohorts could help improving the prognosis of patients with IE. Objective To describe the characteristics and outcomes of left-sided IE and to determine the risk factors associated to in-hospital mortality in a high-volume center. Methods From 15 September 2020 to 15 February 2023, all patients with left-sided IE managed in a tertiary center of cardiology were included in this prospective, observational study. The diagnosis of IE was made according to current guidelines and management was collegially discussed by the endocarditis team. Determinants of in-hospital death were assessed using a multivariate logistic regression model including any covariate associated in univariate analysis (p&amp;lt;0.1). Results A total of 185 patients were included during the study period. Median age was 68 [56 – 76] years, 141 (76%) patients were males, and 75 (41%) cases involved a prosthetic valve. Aortic valve, mitral valve and involvement of both valves were observed in 111 (60%), 48 (26%) and 26 (14%) patients, respectively. Multimodal cardiac imaging, including cardiac computed tomography (CT) and/or PET-FDG, was used in 64 (35%) of all cases, and 49/75 (65%) patients with valvular prosthesis. Severe valvular regurgitation was identified in 56 (30%) patients, root abscess and/or false aneurysms in 57 (31%) patients. A pathogen agent was identified in 169 (91%) patients, and the most frequent germs were Staphylococcus (30%), Streptococcus (30%) and Enterococcus (17%). A severe initial presentation requiring intensive care unit (ICU) admission was observed in 42 (23%) patients. Cardiac surgery was performed in 102 (55%) cases, and 41 (22%) patients required an emergent surgery. A total of 37 (20%) patients died during the initial in-hospital phase, mostly from cardiac or neurovascular causes. In a multivariate analysis, hypertension (Odd ratio (OR) = 3.3; 95% confidence interval (CI): 1.4 – 10), bi-valvular endocarditis (OR = 3.1; 95%CI: 1.0 – 9.5), unidentified pathogen (OR = 4.3; 95%CI: 1.7 – 15) and chronic alcoholic abuse (OR = 16.4; 95%CI: 3.7 – 87.9) were independently associated with increased in-hospital mortality (Table). Conclusion Severe initial presentation requiring an ICU admission and/or urgent cardiac surgery was common among patients with left-sided IE. Chronic alcoholic abuse and unidentified pathogen appear as major determinants of in-hospital mortality.Table

Cellular and Epigenetic Aspects of Trained Immunity and Prospects for Creation of Universal Vaccines in the Face of Increasingly Frequent Pandemics

The inevitability of pandemics creates an urgent requirement for emergency action to develop effective technologies to reduce harm to the human population in the period between the onset of an epidemic and the development and production of a vaccine. In this review we discuss the possibility of engineering universal vaccines. Such vaccines would exploit the nonspecific potential of innate immunity, would allow the population to be vaccinated when an unidentified pathogen appears, and would reduce disease severity until pathogen-specific vaccines become available. There are strong evidences that bacterial or viral vaccines such as BCG, measles and polio have heterologous protective effects against unrelated pathogens. This is attributed to the innate immune system’s ability to maintain the memory of past infections and use it to develop immune defenses against new ones. This effect has been called “trained” immunity. The use of trained immunity may also represent an important new approach to improving existing vaccines or to developing new vaccines that combine the induction of classical adaptive immune memory and innate immune memory. Such approaches can be boosted by genetic technology and prove extremely useful against future pandemics.

Differential CaKAN3-CaHSF8 associations underlie distinct immune and heat responses under high temperature and high humidity conditions

High temperature and high humidity (HTHH) conditions increase plant susceptibility to a variety of diseases, including bacterial wilt in solanaceous plants. Some solanaceous plant cultivars have evolved mechanisms to activate HTHH-specific immunity to cope with bacterial wilt disease. However, the underlying mechanisms remain poorly understood. Here we find that CaKAN3 and CaHSF8 upregulate and physically interact with each other in nuclei under HTHH conditions without inoculation or early after inoculation with R. solanacearum in pepper. Consequently, CaKAN3 and CaHSF8 synergistically confer immunity against R. solanacearum via activating a subset of NLRs which initiates immune signaling upon perception of unidentified pathogen effectors. Intriguingly, when HTHH conditions are prolonged without pathogen attack or the temperature goes higher, CaHSF8 no longer interacts with CaKAN3. Instead, it directly upregulates a subset of HSP genes thus activating thermotolerance. Our findings highlight mechanisms controlling context-specific activation of high-temperature-specific pepper immunity and thermotolerance mediated by differential CaKAN3-CaHSF8 associations.

A Quest for Disease X: Origin, Location, and Mitigation

In February 2018, the World Health Organization (WHO) designated "Disease X" as a placeholder for a hypothetical and unidentified pathogen capable of potentially causing an epidemic in the future. The Covid-19 pandemic that unfolded recently has highlighted the emergence of a highly contagious Disease X, serving as a painful reminder of the potential risks we confront. This article aims to explore the emergence of Disease X, its possible origins, and proposes strategies to improve preparedness for such scenarios. Firstly, Disease X is probably a highly infectious zoonotic virus with RNA as its genetic material. Secondly, factors that may contribute to the emergence of the disease, including population density, ecological deterioration, and medical resources. Finally, barriers to the development of antiviral drugs and vaccines are examined, along with recommendations for social and ecological measures to enhance our preparedness for disease X.

Lophomonas blattarum-like organism in bronchoalveolar lavage from a pneumonia patient: current diagnostic scheme and polymerase chain reaction can lead to false-positive results.

Lophomonas blattarum is an anaerobic protozoan living in the intestine of cockroaches and house dust mites, with ultramicroscopic characteristics such as the presence of a parabasal body, axial filament, and absence of mitochondria. More than 200 cases of Lophomonas infection of the respiratory tract have been reported worldwide. However, the current diagnosis of such infection depends only on light microscopic morphological findings from respiratory secretions. In this study, we attempted to provide more robust evidence of protozoal infection in an immunocompromised patient with atypical pneumonia, positive for Lophomonas-like protozoal cell forms. A direct search of bronchoalveolar lavage fluid via polymerase chain reaction (PCR), transmission electron microscopy (TEM), and metagenomic next-generation sequencing did not prove the presence of protozoal infection. PCR results were not validated with sufficient rigor, while de novo assembly and taxonomic classification results did not confirm the presence of an unidentified pathogen. The TEM results implied that such protozoal forms in light microscopy are actually non-detached ciliated epithelial cells. After ruling out infectious causes, the patient's final diagnosis was drug-induced pneumonitis. These findings underscore the lack of validation in the previously utilized diagnostic methods, and more evidence in the presence of L. blattarum is required to further prove its pathogenicity.

Clinical features and prognostic factors in adults with viral meningitis.

Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.

Influenza A, Influenza B, and SARS-CoV-2 Similarities and Differences - A Focus on Diagnosis.

In late December 2019, the first cases of viral pneumonia caused by an unidentified pathogen were reported in China. Two years later, SARS-CoV-2 was responsible for almost 450 million cases, claiming more than 6 million lives. The COVID-19 pandemic strained the limits of healthcare systems all across the world. Identifying viral RNA through real-time reverse transcription-polymerase chain reaction remains the gold standard in diagnosing SARS-CoV-2 infection. However, equipment cost, availability, and the need for trained personnel limited testing capacity. Through an unprecedented research effort, new diagnostic techniques such as rapid diagnostic testing, isothermal amplification techniques, and next-generation sequencing were developed, enabling accurate and accessible diagnosis. Influenza viruses are responsible for seasonal outbreaks infecting up to a quarter of the human population worldwide. Influenza and SARS-CoV-2 present with flu-like symptoms, making the differential diagnosis challenging solely on clinical presentation. Healthcare systems are likely to be faced with overlapping SARS-CoV-2 and Influenza outbreaks. This review aims to present the similarities and differences of both infections while focusing on the diagnosis. We discuss the clinical presentation of Influenza and SARS-CoV-2 and techniques available for diagnosis. Furthermore, we summarize available data regarding the multiplex diagnostic assay of both viral infections.

Quantitative Electroencephalography Indicators in Children with Acute Purulent Meningitis.

The aim of the present work was to assess the state of brain bioelectrical activity in children during the acute period of bacterial purulent meningitis, with quantitative mathematical analysis of the changes found. The studies included 31 children on days 1 and 6 from onset of illness: 16 children (8.9 ± 2.4 years) admitted to the Pediatric Scientific Clinical Center for Infectious Diseases with laboratory confirmation of diagnoses of purulent meningitis (due to Neisseria meningitidis) (n = 11) or Streptomyces pneumoniae (n = 2) or unidentified pathogen (n = 3)), along with 15 healthy children. Electroencephalogram (EEG) traces were recorded from all these children in the state of calm waking using a Neuron-Spectrum 4/VP 16-channel electroencephalograph. Clinical assessment of the EEG included analysis of background rhythms, zonal differences, and detection of pathological types of activity. Quantitative analysis consisted of the mean power (μV2) and amplitude (μV) of the α, θ, and δ rhythms, along with mean power ratios – α/θ and α/δ. Visual analysis of the EEG in 100% of children in the acute period of purulent meningitis showed diffuse slowing with detection of δ and θ waves. Focal changes in the form of sharp waves were seen in 18.8% of cases (three patients). No cases displayed periodic activity. Meningitis patients showed significant reductions in the α/δ (p = 0.001) and α/θ (p = 0.048) spectral ratios. ROC analysis showed that the α/θ value was <0.18 and the α/δ value was <0.02 (sensitivity 100% and specificity 80%, AUROC 0.9), which may be evidence of the likely development of cerebral edema. Thus, pediatric patients with acute purulent meningitis showed significant impairments to the normal α/θ and α/δ rhythm power ratios on the EEG, which is presumptively explained by suppression of the functional activity of the thalamus and thalamocortical pathways, as well as the reticular formation of the brain.

Bacterial and Fungal Microbiome Profiling in Chilhuacle Negro Chili (Capsicum annuum L.) Associated With Fruit Rot Disease.

Chilhuacle negro chili (Capsicum annuum L.) is an ancient Mexican landrace that is deeply linked to the culinary heritage of the country. Because of the high profitability and uniqueness of this crop, the Universidad Autónoma del Estado de Morelos is exploring its production in controlled environments. In the crop cycles of 2018 to 2019, the production of chilhuacle negro plants was seriously affected by an unidentified pathogen causing fruit rot, which reduced its quality, yield, and market value. Therefore, the main objective of this work was to study and characterize the fruit microbiota, which could help reveal the causal agent of this disease. Using DNA metabarcoding coupled with Illumina and nanopore sequencing technologies, we collected and analyzed both healthy and infected chili fruit, along with greenhouse bioaerosols. We also explored the bacterial and fungal microbiota by using microbiological techniques to isolate some of the culturable bacterial and fungal species. Our results suggest that the seedborne fungus Alternaria alternata is activated during the maturation stage of chilhuacle negro fruit, triggering a microbiome imbalance, which may in turn enable the establishment of other opportunistic pathogenic fungi during fruit decay, such as Mucor sp. To our knowledge, this is the first study of the chilhuacle negro chili microbiome, which can shed some light on our understanding of one of the main diseases that affect this valuable crop.

Kawasaki Disease and Pediatric Infectious Diseases During the Coronavirus Disease 2019 Pandemic

ObjectiveTo assess the epidemiologic association between Kawasaki disease and common pediatric infectious diseases (PIDs) identified during the coronavirus disease 2019 (COVID-19) pandemic period to confirm whether the infection-triggered theory is a plausible hypothesis for the pathogenesis of Kawasaki disease.Study designA retrospective epidemiologic study was conducted using datasets obtained from Web-based surveillance of Kawasaki disease and PIDs in Japan. We compared weekly numbers of patients who developed Kawasaki disease and specific PIDs between 2020 and 2017-2019 and evaluated the association between the percent reduction in the number of patients with these diseases.ResultsA total of 868 patients developed Kawasaki disease in 2020. During the social distancing period in 2020, the number of patients with Kawasaki disease was approximately 35% lower than in 2017-2019. Time from the onset of Kawasaki disease until the first hospital visit did not differ significantly among the examined years. The proportion of older children with Kawasaki disease decreased more than that of infants with Kawasaki disease (age <1 year), resulting in a significant difference in the proportion of infant patients between 2020 and 2017-2019 (24% vs 19%; P < .01). The number of patients with incomplete Kawasaki disease was unchanged from that of previous years. The weekly percent reduction in patient numbers differed between Kawasaki disease and PIDs during 2020, with no strong correlation between the 2 diseases.ConclusionsOur data indicate that parents of patients with Kawasaki disease did not avoid hospital visits during the COVID-19 pandemic period. The findings indicate the possibility that triggering Kawasaki disease might be associated with presently unidentified respiratory pathogen(s) that potentially might be acquired from both within and outside the household.

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects

Splenic infarction and infectious diseases in Korea

BackgroundThe spleen contains immune cells and exhibits a pattern of infarction different from other organs; as such, splenic infarction (SI) may provide important clues to infection. However, the nature of the relationship between SI and infectious disease(s) is not well understood. Accordingly, this retrospective study investigated the relationship between SI and infection.MethodsHospital records of patients with SI, who visited Inha University Hospital (Incheon, Republic of Korea) between January 2008 and December 2018, were reviewed. Patient data regarding clinical presentation, causative pathogens, risk factors, and radiological findings were collected and analyzed.ResultsOf 353 patients with SI, 101 with infectious conditions were enrolled in this study, and their data were analyzed to identify associations between SI and infection. Ten patients were diagnosed with infective endocarditis (IE), and 26 exhibited bacteremia without IE. Twenty-seven patients experienced systemic infection due to miscellaneous causes (negative result on conventional automated blood culture), including the following intracellular organisms: parasites (malaria [n = 12], babesiosis [n = 1]); bacteria (scrub typhus [n = 5]); viruses (Epstein–Barr [n = 1], cytomegalovirus [n = 1]); and unidentified pathogen[s] (n = 7). Splenomegaly was more common among patients with miscellaneous systemic infection; infarction involving other organs was rare. Thirty-eight patients had localized infections (e.g., respiratory, intra-abdominal, or skin and soft tissue infection), and most (35 of 38) had other risk factors for SI.ConclusionsIn this study, various infectious conditions were found to be associated with SI, and intracellular organisms were the most common causative pathogens. Further studies are needed to examine other possible etiologies and the underlying pathophysiological mechanisms.

Nodular-like growth and axial thickening in gorgonians are a defensive response to endolithic cyanobacteria, involving amyloid deposition.

An accurate approach to coral disease study is critical for understanding the global decline of coral populations. Such an approach should involve the proper use of medical concepts and terminology to avoid confusion and promote clarity in the coral disease literature. Inflammatory and neoplastic disorders have been frequently confused in corals. They are both reported as 'growth anomalies' because of their possible gross similarity, but in fact they are very different types of lesions and pathologic phenomena. In this work, we assessed the distribution and prevalence of growth anomalies, externally visible as nodular-like lesions, in the soft corals Eunicella cavolinii and E. singularis in 2008-2009 in 3 different areas along the Campanian coastline of Italy. Histopathology revealed them as chronic inflammatory lesions, resembling chronic inflammatory lesions of vertebrates, encapsulating an unidentified pathogen. Congo red and Masson Fontana histochemistry highlighted an amoebocyte infiltration with the presence of new apposition of melanin coupled with amyloid sheets intended as part of the defensive response, as reported in other invertebrates. A parallel molecular analysis of 16S rRNA of the lesions suggested that the causative agent is an endolithic cyanobacterium belonging to the order Nostocales. This is the first study assessing the presence of amyloid fibrils in corals.

Austerity in the UK and poor health: were deaths directly affected?

A dramatic increase in deaths in the UK since 2011 has defied actuarial forecasts. This has led some to propose a direct link between the rise in deaths and government social care austerity. However, several facts argue against this link. Firstly, age standardised mortality in the second quarter of 2019 was statistically lower than the second quarter in all years since 2001, clearly austerity is still present, but age standardised mortality has recovered. Also, deaths have increased equally across the whole of the UK, whereas social care austerity has largely been restricted to England. English citizens who are residents outside of the UK also show the same trend. These effects are highly reminiscent of a recurring series of disease outbreaks of an unidentified pathogen. In addition, increases in deaths are always linked to increases in hospital admissions. This link arises since around half of a person's lifetime use of acute services is compressed into the last 6 months of life, irrespective of the age at death. This is called the nearness-to-death effect. International research is needed to understand exactly why deaths are behaving in this unique way. While austerity has created a significant problem relating to delayed discharges in hospitals and has highlighted serious problems with how end-of-life care is to be funded, it seemingly cannot be blamed for the increased mortality rate.

How Should We Classify Kawasaki Disease?

The exact classification of Kawasaki disease (KD) has been debated. Infectious disease specialists have claimed it as an infection with a classic immune responses to an as yet unidentified pathogen that localizes to the coronary arteries. Others have favored an autoreactive hypothesis that KD is triggered by an antigen that shares homology with structures in the vascular wall, and molecular mimicry resulting in an immune response directed to that tissue. Rheumatologists have classified it as a systemic vasculitis, while some immunologists have stressed the robust nature of the innate immune response that causes both systemic inflammation as well as damage to the coronary arterial wall and questioned whether KD falls within the spectrum of autoinflammatory diseases. This review will describe the evidences available up to now regarding these hypotheses.