A patient with respiratory toxigenic diphtheria in Greece after more than 30 years.

The introduction of treatment and systematic vaccination has significantly reduced diphtheria mortality; however, toxigenic strains continue to circulate worldwide. The emergence of an indigenous diphtheria case with fatal outcome in Greece, after 30 years, raised challenges for laboratory confirmation, clinical and public health management. Toxigenic Corynebacterium diphtheriae was isolated from an incompletely vaccinated 8-year-old boy with underlying conditions. The child passed away due to respiratory distress syndrome, before the administration of diphtheria antitoxin (DAT). All close contacts in family, school and hospital settings were investigated. Pharyngeal swabs were obtained to determine asymptomatic carriage. Chemoprophylaxis was given for 7 days to all close contacts and a booster dose to those incompletely vaccinated. Testing revealed a classmate, belonging to a subpopulation group (Roma), and incompletely vaccinated, as an asymptomatic carrier with an indistinguishable toxigenic strain (same novel multilocus sequence type, designated ST698). This case highlights the role of asymptomatic carriage, as the entry of toxigenic strains into susceptible populations can put individuals and their environment at risk. Maintenance of high-level epidemiological and microbiological surveillance, implementation of systematic vaccination in children and adults with primary and booster doses, availability of a DAT stockpile, and allowing timely administration are the cornerstone to prevent similar incidents in the future.

Toxigenic Corynebacterium ulcerans associated with upper respiratory infections in cats and dogs.

OBJECTIVES: To describe infection in companion animals with the zoonotic pathogen Corynebacterium ulcerans and to determine its prevalence in clinically-affected and healthy animals. MATERIALS AND METHODS: The clinical presentation and treatment of three cases of C. ulcerans infection is described. Two studies to determine C. ulcerans prevalence rates were undertaken: (a) a prospective study of nasal samples from healthy animals, 479 dogs and 72 cats; (b) a retrospective analysis of records of nasal samples collected over a 10-year period from 189 dogs and 64 cats affected by respiratory signs. RESULTS: Toxigenic C. ulcerans was isolated from four cats with nasal discharge while concurrent C. ulcerans and mecC methicillin-resistant S. aureus infection was detected in a dog suffering from chronic nasal discharge. Clinical features were not distinctive and all cases recovered following antimicrobial treatment. Multilocus sequence typing supported a common source for isolates from the shelter cats. Carriage rates of C. ulcerans in healthy animals were 0.42% (2/479) in dogs and 0.00% (0/72) in cats whereas in animals with signs of upper respiratory tract infection prevalence rates were 0.53% (1/189) in dogs and 6.25% (4/64) in cats. CLINICAL SIGNIFICANCE: Clinicians should be aware that dogs and cats can be infected with (or carriers of) toxigenic C. ulcerans Considering the potential zoonotic risk, assistance from medical and public health colleagues should be sought in confirmed cases.

Seroprevalence of Toxoplasma gondii infection in sheep from northern China.

Toxoplasma gondii is an important zoonotic parasite causing significant health problems to humans and animals. In recent years, a number of investigations about the seroprevalence of T. gondii in China have been reported, but little is known on the prevalence of toxoplasmosis in sheep in northern China. In the present study, a total of 288 sheep serum samples were collected from Inner Mongolia, Heilongjiang, Jilin and Hebei provinces of northern China for T. gondii antibody survey using a latex agglutination test (LAT). Of these, 87 (30.2%) serum samples were positive for antibodies to T. gondii, and the antibody titres ranged from 1:64 to 1:1,024. Seroprevalence of T. gondii infection in sheep was 17.1% in Inner Mongolia, 33.8% in Heilongjiang, 24.6% in Jilin and 46.3% in Hebei. Age and rearing system significantly affected seropositivity. The present survey indicates antibodies to T. gondii are widely prevalent in sheep in northern China, which may cause public health problems in these provinces.

Seroprevalence of Toxoplasma gondii infection in sheep from northern China

@#Toxoplasma gondii is an important zoonotic parasite causing significant health problems to humans and animals. In recent years, a number of investigations about the seroprevalence of T. gondii in China have been reported, but little is known on the prevalence of toxoplasmosis in sheep in northern China. In the present study, a total of 288 sheep serum samples were collected from Inner Mongolia, Heilongjiang, Jilin and Hebei provinces of northern China for T. gondii antibody survey using a latex agglutination test (LAT). Of these, 87 (30.2%) serum samples were positive for antibodies to T. gondii, and the antibody titres ranged from 1:64 to 1:1,024. Seroprevalence of T. gondii infection in sheep was 17.1% in Inner Mongolia, 33.8% in Heilongjiang, 24.6% in Jilin and 46.3% in Hebei. Age and rearing system significantly affected seropositivity. The present survey indicates antibodies to T. gondii are widely prevalent in sheep in northern China, which may cause public health problems in these provinces.

First evidence of Mycoplasma haemocanis in China.

Previous studies show heamotropic Mycoplasma infection frequently occurs among splenectomized, immuno-suppressive or co-infected dog populations. However, in our study, the detection of 162 blood samples from dogs found 3 healthy, female dogs infected with Mycoplasma haemocanis in southeastern China. These infected dogs were grown in dog breeding center and had a history of tick infestation. This is the first molecular report of M. haemocanis in dogs from China. The 16S rRNA gene was partially sequenced and a phylogenetic tree constructed. Mycoplasma spp. was 99.9%-100% identical to the corresponding gene sequences of M. haemocanis and M. haemofelis available in GenBank. In this study, Mycoplasma spp. was identified as M. haemocanis because the bacterium was obtained from dogs.

Molecular detection and genotyping of Anaplasma spp. and Theileria spp. infections in sheep and cattle from the northeast region of China.

Anaplasmosis and theileriosis are significant tick-borne diseases threatening the livestock industry worldwide. In the present study, we screened 127 cattle and 115 sheep blood DNA samples from northeastern China for Theileria and Anaplasma pathogens by polymerase chain reaction (PCR) using species-specific primers. The result showed that only Theileria orientalis and Anaplasma ovis were detected, with a prevalence of 2.9% for T. orientalis in cattle and 57.4% for A. ovis in sheep. Fragments of Anaplasma ovis major surface protein 4 (AoMSP4) and Theileria orientalis major piroplasm surface protein (ToMPSP) genes were sequenced for phylogenetic analysis. Sequence analysis showed that the AoMSP4 gene was conserved, with 100% sequence identity value among sheep samples. However, the ToMPSP gene was relatively diverse, with sequence identity ranging from 87.6%-99l.0% among cattle samples. Phylogenetic analysis showed that the ToMPSP gene sequences isolated from 4 cattle samples were classified into type 1, type 2 and type 7, while the AoMSP4 gene sequences obtained from 66 sheep were classified into genotype I, according to the neighbour-joining distance method. This study provides important data for understanding the epidemiology of tick-borne diseases and genetic diversity of these pathogens in the northeast region of China.

Emergence and molecular characterisation of non-toxigenic tox gene-bearing Corynebacterium diphtheriae biovar mitis in the United Kingdom, 2003-2012.

Non-toxigenic Corynebacterium diphtheriae have become increasingly recognised as emerging pathogens across Europe causing severe invasive disease. A subset of non-toxigenic C. diphtheriae are 'non-toxigenic tox gene-bearing' (NTTB) strains; these strains are genotypically toxpositive, but do not express the protein. The circulation of NTTB strains was first observed during the 1990s upsurge of diphtheria in Eastern Europe but has not been reported in other European countries. Circulation of NTTB strains could be considered an increased risk for diphtheria and other related diseases, given their possible role as a tox gene reservoir with the theoretical risk of re-emerging toxin expression. Here we report the characterisation of 108 non-toxigenic C. diphtheriae biovar mitis isolates submitted to the World Health Organization (WHO) Global Reference Centre for Diphtheria at Public Health England, London, between 2003 and 2012, in order to determine the presence of NTTB strains. Using molecular methods, five NTTB isolates were identified; four human isolates (MLST type 212) and one isolate from a companion cat (MLST type 40). The emergence of these strains could indicate continuation of the circulation of potentially toxigenic strains and appropriate laboratory diagnostic methods should be used for detection. Given the complacency that currently exists in Europe awareness with regards to diphtheria diagnostics must be enhanced.

Access to diphtheria antitoxin for therapy and diagnostics.

The most effective treatment for diphtheria is swift administration of diphtheria antitoxin (DAT) with conjunct antibiotic therapy. DAT is an equine immunoglobulin preparation and listed among the World Health Organization Essential Medicines. Essential Medicines should be available in functioning health systems at all times in adequate amounts, in appropriate dosage forms, with assured quality, and at prices individuals and the community can afford. However, DAT is in scarce supply and frequently unavailable to patients because of discontinued production in several countries, low economic viability, and high regulatory requirements for the safe manufacture of blood-derived products. DAT is also a cornerstone of diphtheria diagnostics but several diagnostic reference laboratories across the European Union (EU) and elsewhere routinely face problems in sourcing DAT for toxigenicity testing. Overall, global access to DAT for both therapeutic and diagnostic applications seems inadequate. Therefore--besides efforts to improve the current supply of DAT--accelerated research and development of alternatives including monoclonal antibodies for therapy and molecular-based methods for diagnostics are required. Given the rarity of the disease, it would be useful to organise a small stockpile centrally for all EU countries and to maintain an inventory of DAT availability within and between countries.

Increase in scarlet fever notifications in the United Kingdom, 2013/2014.

Increases in scarlet fever above usual seasonal levels are currently being seen across the United Kingdom. Medical practitioners have been alerted to the exceptional increase in incidence. Given the potential for this to signal a population increase in invasive group A streptococcal disease, close monitoring of invasive disease is essential.

Toxigenic Corynebacterium ulcerans in human and non-toxigenic Corynebacterium diphtheriae in cat.

Corynebacterium diphtheriae and Corynebacterium ulcerans are rarely isolated from clinical samples in Belgium. A case of toxigenic C. ulcerans in a woman is described, which confirms that this pathogen is still present. During investigation of the patient's cats, only a non-toxigenic toxin-bearing C. diphtheriae strain was detected.

Identification of group A streptococcal emm types commonly associated with invasive infections and antimicrobial resistance by the use of multiplex PCR and high-resolution melting analysis.

M/emm typing, based either on serotyping of the M protein or on sequencing of the emm gene, is a major tool for epidemiological studies of group A streptococci (GAS). In order to simplify M/emm typing, we designed two multiplex polymerase chain reaction (PCR) formats capable of identifying the most frequent GAS M/emm types involved in invasive infections and antimicrobial resistance. A heptaplex PCR procedure was first developed in a conventional format coupled with gel electrophoresis to identify emm types 1, 3, 4, 6, 12, 28, and 89, based on the size of the amplification products. The other method, designed to identify the same seven emm types, together with emm11, was based on a real-time PCR format coupled with high-resolution melting (HRM) analysis, allowing the rapid typing of large strain collections.

Prevention of group B streptococcal neonatal disease revisited. The DEVANI European project.

The purpose of this paper was to present the current knowledge on the prevention of group B streptococcus (GBS) neonatal infections and the status of prevention policies in European countries and to present the DEVANI pan-European program, launched in 2008. The aim of this program was to assess the GBS neonatal infection burden in Europe, to design a new vaccine to immunize neonates against GBS infections, to improve the laboratory performance for the diagnosis of GBS colonization and infection, and to improve the methods for the typing of GBS strains. The current guidelines for GBS prevention in different countries were ascertained and a picture of the burden before and after the instauration of prevention policies has been drawn. After the issue of the Centers for Disease Control and Prevention (CDC) guidelines, many European countries have adopted universal screening for the GBS colonization of pregnant women and intrapartum prophylaxis to colonized mothers. Nevertheless, some European countries continue advocating the risk factor approach to GBS prevention. Most European countries have implemented policies to prevent GBS neonatal infections and the burden of the disease has decreased during the last several years. Nevertheless, further steps are necessary in order to develop new strategies of prevention, to improve microbiological techniques to detect GBS colonization and infection, and to coordinate the prevention policies in the EU.

Streptococcus pyogenes cluster in a care home in England April to June 2010.

Two fatal cases of Streptococcus pyogenes emm st22.6 bacteraemia occurred in a care home in England during April and June 2010, initiating a cluster investigation. The first case had left the home 13 days before the second case took up residence. We sought further cases and carriers. We swabbed throat and chronic skin lesions from residents and staff and examined these specimens for the presence of S. pyogenes. 61 specimens were taken from 18 of 19 residents and 39 of 39 staff. All results from swabbing were culture negative. We observed infection control practices and the environment at the care home for deficiencies. Issues were identified relating to the correct use of personal protective equipment, hand hygiene, clinical waste and laundry. Infection control practices were improved and training given. Infection control practices and the environment at a care home should be examined as part of the investigation of a S. pyogenes cluster. Screening for carriage of S. pyogenes should be done before antibiotic chemoprophylaxis is issued to care home residents and staff.

A quantitative descriptive study of the prevalence of carriage (colonisation) of haemolytic streptococci groups A, B, C and G in pregnancy.

Invasive group B streptococcus (GBS) disease is a leading cause of neonatal death. There is no UK national screening programme for GBS in pregnancy, hence colonisation rates are unknown. Intrapartum antibiotic prophylaxis is given during labour to colonised women to reduce neonatal GBS transmission and subsequent invasive infection. Data about prevalence of other haemolytic streptococci in pregnancy, including group A streptococcus (GAS), are uncommon despite increasing importance. This study investigated colonisation in 100 pregnant women using conventional culture methods; 19% had GBS. This suggests that GBS carriage is common in the UK. The role of other ß-haemolytic streptococci remains undefined.

Increase in invasive Streptococcus pyogenes and Streptococcus pneumoniae infections in England, December 2010 to January 2011.

Increases in invasive Streptococcus pyogenes and S. pneumoniae above the seasonally expected levels are currently being seen in England. Preliminary analyses suggest that the high level of influenza activity seen this winter may be contributing to an increased risk of concurrent invasive bacterial and influenza infections in children and young adults.

Group A streptococcal infections during the seasonal influenza outbreak 2010/11 in South East England.

We present a series of 19 cases of invasive Group A streptococcal (iGAS) infection reported to the Thames Valley Health Protection Unit from 1 December 2010 to 15 January 2011. Ten patients died and a prodrome of influenza-like illness was reported in 14 cases.Influenza B co-infection was confirmed in four cases,three of which were fatal. Our report provides further evidence that influenza B co-infection with iGAS has the potential to cause significant morbidity and mortality.

Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007-2008: a multicentre European study.

Diphtheria is now rare in most European countries but, when cases do arise, the case fatality rate is high (5-10%). Because few countries continue to routinely screen for the causative organisms of diphtheria, the extent to which they are circulating amongst different European populations is largely unknown. During 2007-2008, ten European countries each screened between 968 and 8551 throat swabs from patients with upper respiratory tract infections. Six toxigenic strains of Corynebacterium diphtheriae were identified: two from symptomatic patients in Latvia (the country with the highest reported incidence of diphtheria in the European Union) and four from Lithuania (two cases, two carriers); the last reported case of diphtheria in Lithuania was in 2002. Carriage rates of non-toxigenic organisms ranged from 0 (Bulgaria, Finland, Greece, Ireland, Italy) to 4.0 per 1000 (95% CI 2.0-7.1) in Turkey. A total of 28 non-toxigenic strains were identified during the study (26 C. diphtheriae, one Corynebacterium ulcerans, one Corynebacterium pseudotuberculosis). The non-toxigenic C. ulcerans strain was isolated from the UK, the country with the highest reported incidence of cases due to C. ulcerans. Of the eleven ribotypes detected, Cluj was seen most frequently in the non-toxigenic isolates and, amongst toxigenic isolates, the major epidemic clone, Sankt-Petersburg, is still in circulation. Isolation of toxigenic C. diphtheriae and non-toxigenic C. diphtheriae and C. ulcerans in highly-vaccinated populations highlights the need to maintain microbiological surveillance, laboratory expertise and an awareness of these organisms amongst public health specialists, microbiologists and clinicians.

Diphtheria in the United Kingdom, 1986-2008: the increasing role of Corynebacterium ulcerans.

Diphtheria is an uncommon disease in the UK due to an effective immunization programme; consequently when cases do arise, there can be delays in diagnosis and case-fatality rates remain high. We reviewed 102 patients with infections caused by toxigenic corynebacteria (an average of four per year) reported in the UK between 1986 and 2008: 42 Corynebacterium diphtheriae, 59 C. ulcerans and one C. pseudotuberculosis, as well as 23 asymptomatic carriers. Five fatalities were reported, all in unvaccinated patients. The major risk factor for C. diphtheriae infection continued to be travel to an endemic country. C. ulcerans infections became more common than C. diphtheriae infections in the UK; they were associated with contact with companion animals. The occurrence of indigenous severe C. ulcerans infections and imported C. diphtheriae cases highlights the need to maintain UK routine vaccination coverage at the 95% level in the UK, as recommended by the World Health Organization.

Toxigenic Corynebacterium ulcerans infection in a veterinary student in London, United Kingdom, May 2010.

We report on a case of toxigenic Corynebacterium ulcerans infection in a fully immunised veterinary student, investigated in London, United Kingdom, in May 2010. There was no ongoing transmission in human contacts. Possible animal sources were identified.