A comprehensive list of bacterial pathogens infecting humans.

There exists an enormous diversity of bacteria capable of human infection, but no up-to-date, publicly accessible list is available. Combining a pragmatic definition of pathogenicity with an extensive search strategy, we report 1513 bacterial pathogens known to infect humans described pre-2021. Of these, 73 % were regarded as established (have infected at least three persons in three or more references) and 27 % as putative (fewer than three known cases). Pathogen species belong to 10 phyla and 24 classes scattered throughout the bacterial phylogeny. We show that new human pathogens are discovered at a rapid rate. Finally, we discuss how our results could be expanded to a database, which could provide a useful resource for microbiologists. Our list is freely available and archived on GitHub and Zenodo and we have provided walkthroughs to facilitate access and use.

Staphylococcus cornubiensis sp. nov., a member of the Staphylococcus intermedius Group (SIG).

We here describe a novel species in the Staphylococcus intermedius Group (SIG) which is phenotypically similar to Staphylococcus pseudintermedius but is genomically distinct from it and other SIG members, with an average nucleotide identity of 90.2 % with its closest relative S. intermedius. The description of Staphylococcus cornubiensis sp. nov. is based on strain NW1T (=NCTC 13950T=DSM 105366T) isolated from a human skin infection in Cornwall, UK. Although pathogenic, NW1T carries no known virulence genes or mobilizable antibiotic resistance genes and further studies are required to assess the prevalence of this species in humans as well as its potential presence in companion animals.

Hepatitis E seroprevalence in the Americas: A systematic review and meta-analysis.

BACKGROUND & AIMS: While hepatitis E virus infections are a relevant topic in Europe, knowledge about epidemiology of hepatitis E virus infections in the USA and Latin America is still limited. Aim of this study was to estimate anti-hepatitis E virus IgG seroprevalence in the Americas and to assess whether low socioeconomic status is associated with hepatitis E virus exposure. METHODS: We performed a systematic review and meta-analysis. Literature search was performed in PubMed for articles published 01/1994-12/2016. Prevalence was estimated using a mixed-effects model and reported in line with PRISMA reporting guidelines. RESULTS: Seroprevalence was significantly higher in the USA than in Latin America, independently of assay, patient cohort, methodological quality or study year (OR: 1.82 (1.06-3.08), P = .03). Patients in the USA had a more than doubled estimated seroprevalence (up to 9%, confidence interval 5%-15.6%) than those in Brazil (up to 4.2%, confidence interval 2.4%-7.1%; OR: 2.27 (1.25-4.13); P = .007) and Mixed Caribbean (up to 1%, OR: 8.33 (1.15-81.61); P = .04). A comparison with published data from Europe demonstrated that anti-hepatitis E virus seroprevalence in the USA and Europe did not differ significantly (OR: 1.33 (0.81-2.19), P = .25), while rate in South America was significantly lower than that in Europe (OR: 0.67 (0.45-0.98), P = .04). CONCLUSIONS: Hepatitis E virus is common in the USA. Surprisingly, the risk of hepatitis E virus exposure was low in many South American countries. Seroprevalence did not differ significantly between Europe and the USA. Hence, hepatitis E virus is not limited to countries with low sanitary standards, and a higher socioeconomic status does not protect populations from hepatitis E virus exposure.

Clinical phenotype and outcome of hepatitis E virus-associated neuralgic amyotrophy.

OBJECTIVE: To determine the clinical phenotype and outcome in hepatitis E virus-associated neuralgic amyotrophy (HEV-NA). METHODS: Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection. RESULTS: Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12-2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months. CONCLUSIONS: Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted.

Hepatitis E virus infection and acute non-traumatic neurological injury: A prospective multicentre study.

BACKGROUND & AIMS: Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury. METHODS: Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands. RESULTS: Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8-145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus. CONCLUSIONS: In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted. Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system.

Investigation of liver dysfunction: who should we test for hepatitis E?

AIM: Hepatitis E virus (HEV) is endemic in developed countries, but unrecognized infection is common. Many national guidelines now recommend HEV testing in patients with acute hepatitis irrespective of travel history. The biochemical definition of 'hepatitis' that best predicts HEV infection has not been established. This study aimed to determine parameters of liver biochemistry that should prompt testing for acute HEV. METHODS: This was a retrospective study of serial liver function tests (LFTs) in cases of acute HEV (n=74) and three comparator groups: common bile duct stones (CBD, n=87), drug-induced liver injury (DILI, n=69) and patients testing negative for HEV (n=530). To identify the most discriminating parameters, LFTs from HEV cases, CBD and DILI were compared. Optimal LFT cutoffs for HEV testing were determined from HEV true positives and HEV true negatives using receiver operating characteristic curve analysis. RESULTS: Compared with CBD and DILI, HEV cases had a significantly higher maximum alanine aminotransferase (ALT) (P<0.001) and ALT/alkaline phosphatase (ALKP) ratio (P<0.001). For HEV cases/patients testing negative for HEV, area under receiver operating characteristic curve was 0.805 for ALT (P<0.001) and 0.749 for the ALT/ALKP ratio (P<0.001). Using an ALT of at least 300 IU/l to prompt HEV testing has a sensitivity of 98.6% and a specificity of 30.3% compared with an ALT/ALKP ratio higher than or equal to 2 (sensitivity 100%, specificity 9.4%). CONCLUSION: Patients with ALT higher than or equal to 300 IU/l should be tested for HEV. This is simple, detects nearly all cases and requires fewer samples to be tested than an ALT/ALKP ratio higher than or equal to 2. Where clinically indicated, patients with an ALT less than 300 IU/l should also be tested, particularly if HEV-associated neurological injury is suspected.

Characterization of the Specificity, Functionality, and Durability of Host T-Cell Responses Against the Full-Length Hepatitis E Virus.

The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel "Quantiferon" assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and 27 healthy volunteers. A genotype 3a peptide library (616 overlapping peptides spanning open reading frames [ORFs] 1-3) was used in interferon-gamma (IFN-γ) T-cell ELISpot assays. CD4+ /CD8+ T-cell subsets and polyfunctionality were defined using ICCS and SPICE analysis. Quantification of IFN-γ used whole-blood stimulation with recombinant HEV-capsid protein in the QuantiFERON kit. HEV-specific T-cell responses were detected in 41/44 immune-competent HEV exposed volunteers (median magnitude: 397 spot-forming units/106 peripheral blood mononuclear cells), most frequently targeting ORF2. High-magnitude, polyfunctional CD4 and CD8+ T cells were detected during acute disease and maintained to 12 years, but these declined over time, with CD8+ responses becoming more monofunctional. Low-level responses were detectable in immunosuppressed patients. Twenty-three novel HEV CD4+ and CD8+ T-cell targets were mapped predominantly to conserved genomic regions. QuantiFERON testing demonstrated an inverse correlation between IFN-γ production and the time from clinical presentation, providing 100% specificity, and 71% sensitivity (area under the receiver operator characteristic curve of 0.86) for HEV exposure at 0.3 IU/mL. CONCLUSION: Robust HEV-specific T-cell responses generated during acute disease predominantly target ORF2, but decline in magnitude and polyfunctionality over time. Defining HEV T-cell targets will be important for the investigation of HEV-associated autoimmune disease. (Hepatology 2016;64:1934-1950).

Coastal clustering of HEV; Cornwall, UK.

BACKGROUND AND AIMS: Autochthonous hepatitis E virus (HEV) infection is a porcine zoonosis and increasingly recognized in developed countries. In most cases the route of infection is uncertain. A previous study showed that HEV was associated geographically with pig farms and coastal areas. AIM: The aim of the present research was to study the geographical, environmental and social factors in autochthonous HEV infection. METHODS: Cases of HEV genotype 3 infection and controls were identified from 2047 consecutive patients attending a rapid-access hepatology clinic. For each case/control the following were recorded: distance from home to nearest pig farm, distance from home to coast, rainfall levels during the 8 weeks before presentation, and socioeconomic status. RESULTS: A total of 36 acute hepatitis E cases, 170 age/sex-matched controls and 53 hepatitis controls were identified. The geographical spread of hepatitis E cases was not even when compared with both control groups. Cases were more likely to live within 2000 m of the coast (odds ratio=2.32, 95% confidence interval=1.08-5.19, P=0.03). There was no regional difference in the incidence of cases and controls between west and central Cornwall. There was no difference between cases and controls in terms of distance from the nearest pig farm, socioeconomic status or rainfall during the 8 weeks before disease presentation. CONCLUSION: Cases of HEV infection in Cornwall are associated with coastal residence. The reason for this observation is uncertain, but might be related to recreational exposure to beach areas exposed to HEV-contaminated 'run-off' from pig farms. This hypothesis merits further study.

Hepatitis E virus and neurological injury.

Hepatitis E is hyperendemic in many developing countries in Asia and Africa, and is caused by hepatitis E virus (HEV) genotypes 1 and 2, which are spread via the faecal-oral route by contaminated water. Recent data show that HEV infection is also endemic in developed countries. In such geographical settings, hepatitis E is caused by HEV genotypes 3 and 4, and is mainly a porcine zoonosis. In a minority of cases, HEV causes acute and chronic hepatitis, but infection is commonly asymptomatic or unrecognized. HEV infection is associated with a number of extrahepatic manifestations, including a range of neurological injuries. To date, 91 cases of HEV-associated neurological injury--most commonly, Guillain-Barré syndrome, neuralgic amyotrophy, and encephalitis/myelitis--have been reported. Here, we review the reported cases, discuss possible pathogenic mechanisms, and present our perspectives on future directions and research questions.

Hepatitis E virus seroprevalence in three hyperendemic areas: Nepal, Bangladesh and southwest France.

BACKGROUND: Hepatitis E causes a significant burden of disease in developing countries and has recently been increasingly recognized in developed countries. Comparing population anti-hepatitis E virus (HEV) seroprevalence across populations has been difficult. OBJECTIVES: The aim of this study was to compare the anti-HEV IgG seroprevalence in both adults and children in three hyper-endemic areas (Nepal, Bangladesh and southwest France) using a sensitive, commercial anti-HEV IgG assay. STUDY DESIGN: Serum or plasma from adults and children in Nepal (n=498), Bangladesh (n=1,009) and Southwest France (n=1031) were tested for anti-HEV IgG using the Wantai assay. RESULTS: After age-standardization, anti-HEV IgG seroprevalence was 47.1%, 49.8% and 34.0% in Nepal, Bangladesh and southwest France, respectively. There was no difference in seroprevalence by gender in any of the countries. A paucity of infections in children 1-10 years-old was consistently observed (less than 15%) at all 3 locations. CONCLUSIONS: Surprisingly similar high rates of anti-HEV antibodies were detected using a common, sensitive assay. Despite differences in the epidemiology and circulating genotype of HEV in Nepal, Bangladesh and southwest France, this study found more similarities in population seroprevalence than expected.

Improved detection of Staphylococcus intermedius group in a routine diagnostic laboratory.

The Staphylococcus intermedius group (SIG) includes zoonotic pathogens traditionally associated with dog bites. We describe a simple scheme for improved detection of SIG using routine laboratory methods, report its effect on isolation rates, and use sequencing to confirm that, apart from one atypical SIG strain, most isolates are Staphylococcus pseudintermedius.

Molecular epidemiology of ascariasis: a global perspective on the transmission dynamics of Ascaris in people and pigs.

BACKGROUND: The roundworm Ascaris lumbricoides infects 0.8 billion people worldwide, and Ascaris suum infects innumerable pigs across the globe. The extent of natural cross-transmission of Ascaris between pig and human hosts in different geographical settings is unknown, warranting investigation. METHODS: Adult Ascaris organisms were obtained from humans and pigs in Europe, Africa, Asia, and Latin America. Barcodes were assigned to 536 parasites on the basis of sequence analysis of the mitochondrial cytochrome c oxidase I gene. Genotyping of 410 worms was also conducted using a panel of microsatellite markers. Phylogenetic, population genetic, and Bayesian assignment methods were used for analysis. RESULTS: There was marked genetic segregation between worms originating from human hosts and those originating from pig hosts. However, human Ascaris infections in Europe were of pig origin, and there was evidence of cross-transmission between humans and pigs in Africa. Significant genetic differentiation exists between parasite populations from different countries, villages, and hosts. CONCLUSIONS: In conducting an analysis of variation within Ascaris populations from pig and human hosts across the globe, we demonstrate that cross-transmission takes place in developing and developed countries, contingent upon epidemiological potential and local phylogeography. Our results provide novel insights into the transmission dynamics and speciation of Ascaris worms from humans and pigs that are of importance for control programs.

Neuralgic amyotrophy and hepatitis E virus infection.

OBJECTIVE: To determine whether there is an association between an acute preceding hepatitis E virus (HEV) infection and neuralgic amyotrophy (NA), and if so, whether patients with HEV-related NA differ from patients without an associated HEV infection. METHODS: HEV testing was conducted in a retrospective cohort of 28 Cornish patients with NA (2011-2013) and a prospective cohort of 38 consecutive Dutch patients with NA (2004-2007). Acute-phase serum samples were analyzed for the presence of anti-HEV immunoglobulin (Ig) M and IgG and HEV RNA (quantitative real-time PCR). RESULTS: Five cases (10.6%) of acute hepatitis E infection were identified in a total group of 47 patients with NA of whom serum samples were available. In 4 patients, HEV RNA was detected in serum samples taken at presentation. All patients with HEV-associated NA had clinical and electrophysiologic evidence of bilateral brachial plexus involvement. Anti-HEV IgM positivity was not related to age, sex, disease severity, disease course, or outcome. CONCLUSIONS: Acute hepatitis E is found in 10% of patients with NA from the United Kingdom and the Netherlands. Further research is required to investigate the role of HEV in NA in other geographical locations and to determine pathophysiologic mechanisms.

Hepatitis E.

PURPOSE OF REVIEW: Hepatitis E has been regarded as a disease of the developing world, where it causes large waterborne outbreaks and sporadic cases of hepatitis. Recent research has shown this received wisdom to be mistaken. RECENT FINDINGS: Recent studies have shown that authochtonous (locally acquired) hepatitis E does occur in developed countries, is caused by hepatitis E virus (HEV) genotypes 3 and 4, and is zoonotic with pigs as the primary host. Most infections are clinically inapparent. However, acute symptomatic hepatitis E has a predilection for middle-aged and elderly men, with an excess mortality in patients with underlying chronic liver disease. Chronic infection occurs in the immunosuppressed with rapidly progressive cirrhosis if untreated, the treatment of choice being ribavirin monotherapy for 3 months. Hepatitis E has a range of extra-hepatic manifestations, including a spectrum of neurological syndromes. HEV can be transmitted by blood transfusion and has recently been found in donated blood in a number of countries. SUMMARY: The diagnosis should be considered in any patient with a raised alanine aminotranferase, irrespective of age or travel history. The safety of blood products needs to be fully assessed, as a matter of priority, as blood donors are not currently screened for HEV.

Clinical and laboratory features and natural history of seronegative hepatitis in a nontransplant centre.

BACKGROUND: Seronegative hepatitis is a recognized cause of liver failure requiring transplantation. The aetiology is unknown, but might relate to an unidentified virus or immune dysregulation. There are few data on seronegative hepatitis presenting to nontransplant centres. OBJECTIVES: To describe the clinical/laboratory features and natural history of seronegative hepatitis and compare these with viral/autoimmune hepatitis. METHODS: Cases of seronegative, viral and autoimmune hepatitis were identified from 2080 consecutive patients attending a rapid-access jaundice clinic over a 14-year period. RESULTS: Of 881 patients with hepatocellular jaundice, 27 (3%) had seronegative hepatitis, 44 (5%) autoimmune and 62 (7%) viral hepatitis (acute hepatitis A, B, C and E viruses). Fifteen out of 27 (56%) patients with seronegative hepatitis were male, median age 60 years (range 14-74). Peak bilirubin was 63 µmol/l (range 9-363), alanine aminotransferase 932 IU/l (range 503-3807). Duration of illness was 7 weeks (range 4-12). No patients developed liver failure or had further bouts of hepatitis. One patient developed acute lymphoblastic leukaemia shortly after presentation.There was no difference in age/sex of patients with seronegative hepatitis and those with viral hepatitis. Compared with autoimmune hepatitis (age 65 years, range 15-91), patients with seronegative hepatitis were younger (P=0.002) and more likely to be male (P=0.004). Patients with autoimmune hepatitis were more likely (P<0.0001) to have an albumin less than 35 g/l, international normalized ratio greater than 1.2, raised IgG and positive antinuclear/smooth muscle antibody, compared with patients with seronegative hepatitis. CONCLUSION: Seronegative hepatitis presenting to a nontransplant centre is generally a self-limiting illness. The aetiology is more likely to be viral than autoimmune.

Hepatitis E seroprevalence in recipients of renal transplants or haemodialysis in southwest England: a case-control study.

Locally acquired HEV infection is increasingly recognized in developed countries. Anti-HEV IgG seroprevalence has been shown to be high in haemodialysis patients in a number of previous studies, employing assays of uncertain sensitivity. The aim of this study was to investigate anti-HEV IgG seroprevalence in recipients of haemodialysis and renal transplants compared to a control group using a validated, highly sensitive assay. Eighty-eight patients with functioning renal transplants and 76 receiving chronic haemodialysis were tested for HEV RNA and anti-HEV IgG and IgM. Six hundred seventy controls were tested for anti-HEV IgG. Anti-HEV IgG was positive in 28/76 (36.8%) of haemodialysis and 16/88 (18.2%) of transplant patients. HEV RNA was not found in any patient. 126/670 (18.8%) of control subjects were anti-HEV IgG positive. After adjusting for age and sex, there was a significantly higher anti-HEV IgG seroprevalence amongst haemodialysis patients compared to controls (OR = 1.97, 95% CI = 1.16-3.31, P = 0.01) or transplant recipients (OR = 2.63, 95% CI = 1.18-6.07, P = 0.02). Patients with a functioning transplant showed no difference in anti-HEV IgG seroprevalence compared to controls. The duration of haemodialysis or receipt of blood products were not significant risk factors for HEV IgG positivity. Patients receiving haemodialysis have a higher seroprevalence of anti-HEV IgG than both age- and sex-matched controls and a cohort of renal transplant patients. None of the haemodialysis patients had evidence of chronic infection. The reason haemodialysis patients have a high seroprevalence remains uncertain and merits further study.

Hepatitis E.

Hepatitis E virus (HEV) was discovered during the Soviet occupation of Afghanistan in the 1980s, after an outbreak of unexplained hepatitis at a military camp. A pooled faecal extract from affected soldiers was ingested by a member of the research team. He became sick, and the new virus (named HEV), was detected in his stool by electron microscopy. Subsequently, endemic HEV has been identified in many resource-poor countries. Globally, HEV is the most common cause of acute viral hepatitis. The virus was not initially thought to occur in developed countries, but recent reports have shown this notion to be mistaken. The aim of this Seminar is to describe recent discoveries regarding HEV, and how they have changed our understanding of its effect on human health worldwide.

Hepatitis E virus antibodies in blood donors, France.

Using a validated sensitive assay, we found hepatitis E virus (HEV) IgG in 52.5% of voluntary blood donors in southwestern France. This finding suggests HEV is highly endemic to this region. The high HEV prevalence may reflect local dietary practices, such as eating uncooked pork and game products.