Outbreak Investigations

During 2003 and 2004, the Units of RSIL assisted in the investigation of 53 outbreaks (or possible outbreaks) of infections within our remit. In all, 605 outbreak-related samples and specimens were received and examined. The most common question posed is the relatedness or otherwise of collections of organisms isolated from patients and environments in community or hospital-associated clusters of infections. Conventional - usually serotyping - and molecular epidemiological typing methods are used and results interpreted in terms of the likelihood that cultures from different patients and/or places represent the same strain. In this way potential sources of infection, be they human or environmental, can be identified with reliability and the necessary control measures implemented. It should be noted that not all suspect outbreaks are confirmed as such, nor indeed are all potential members of a cluster or outbreak confirmed as belonging to the main cluster. The most common requests for outbreak assistance during this period were group A streptococcus, group B streptococcus, Legionella pneumophila, Streptococcus pneumoniae, C.diphtheriae, Bordetella pertussis and other streptococcus.

Highlights

November 2007

Steering Committee Meeting for the European Diphtheria Surveillance Network: DIPNET

DIPNET is a 2 million Euro, three year European Commission funded programme coordinated by the HPA Respiratory and Systemic Infection Laboratory and the Immunisation Department at the Centre for Infections. An evaluation of current and future activities of the network was undertaken at the Second DIPNET Steering Committee Meeting, held on 13-14 November in Istanbul, Turkey. The UK, Bulgaria, Finland, France, Greece, Italy, Latvia, Lithuania, Netherlands, Romania, Slovenia, Turkey and WHO EURO were all represented at the meeting. In addition, ECDC representatives participated by video link.

DIPNET’s first year achievements include the launch of the new DIPNET web-site, an assessment of surveillance and diphtheria reference microbiology capacities in EU member states a laboratory diagnostics External Quality Assurance exercise and two international laboratory diagnostic workshops, both held at CfI. Year two’s activities include development of a web-enabled integrated surveillance and microbiology database, assessment of serological immunity to diphtheria amongst EU populations, and a unique screening study to assess carriage of corynebacteria in different DIPNET member countries.

The variable accessibility of diphtheria anti-toxin for therapeutic use in the EU was also discussed, and further work is in hand to identify and make available information about current suppliers. Findings from this project will contribute towards updating the WHO Manuals for the Laboratory Diagnosis and Management and Control of Diphtheria that were written by the then Public Health Laboratory Service in 1994.

Further information about DIPNET’s activities, including forthcoming events, is available at www.dipnet.org

August 2007

New Legionella pneumophila study

CfI has been awarded a grant from the Health and Safety Executive to investigate the question “Are some strains of Legionella pneumophila more likely to cause human disease than others, and if so, are these strains more prevalent in some environmental reservoirs compared to others”. This joint HPA-HSE project will use the newly described DNA sequence based typing methods developed over recent years by a CfI led European consortium of national reference laboratories. These methods, together with an extensive suite of on-line database and quality assurance tools, mean that L. pneumophila typing is now standardized globally. It is anticipated that this study will identify 1) whether some strains are more likely to cause disease than are others and 2) whether there is a relationship between particular L. pneumophila strain and the specific environments in which they are encountered. If these data indicate that there is an enhanced frequency of detection of more virulent strains in certain environmental reservoirs, then policy makers will be in a position to make more informed decisions regarding resource allocation for Legionella control. For example, should the study show that a higher proportion of strains associated with disease are found in a particular risk system then the findings will influence future intervention strategies.

July 2007

New enhanced surveillance test for pertussis

The Respiratory and Systemic Infection Laboratory and Immunisation Department of CfI have launched a new enhanced surveillance test for pertussis this month. This test is used to estimate IgG antibody levels in oral fluid directed against Bordetella pertussis pertussis toxin (PT). A pilot study of testing oral fluid from notified cases of pertussis was carried out by in two areas of the country (Thames Valley and Leicestershire) and was found to be acceptable to staff in the HPUs, GPs and patients. RSIL is now providing this service to diagnose notified cases who have been coughing for >2 weeks and HPUs have been invited to promote the investigation of all such cases that have not already been confirmed by other methods (culture, PCR or serology). It is hoped that by seeking laboratory confirmation of notified cases, the sensitivity of surveillance will increase and estimates of the incidence of pertussis will be a made more robust.

May 2007

Launch of the Diphtheria Surveillance Network DIPNET

DIPNET has been launched with the aim “to establish a network of expertise for the prevention of diphtheria and other related infections” across all EU member state countries. The network arises from an expansion of the European Laboratory Working Group on Diphtheria (ELWGD), which was set up in 1993 in response to the re-emergence of diphtheria to epidemic levels in the Russian Federation and Newly Independent States (NIS) in the 1990s. A successful feasibility study for DIPNET was carried out between December 2001 and October 2003, which led to the launch of DIPNET at the Ninth International meeting of the ELWGD and DIPNET at Vouliagmeni, Greece in November 2006. DIPNET is funded by EC-DG SANCO and was officially recognised by the European Commission as a Dedicated Surveillance Network in November 2006. 25 Member States are participating, in addition, there are 20 non-EU collaborating countries. involved actively

The DIPNET programme is organised into nine work packages, eight of which will be coordinated by the HPA Centre for Infections, and the ninth by the Istituto Superiore di Sanita in Italy. DIPNET is working closely with the European Centre for Disease Prevention and Control (ECDC) across all work packages, in collaboration with WHO EURO. Development of study protocols for these work packages is currently underway. There will be a DIPNET European workshop on the laboratory diagnosis of diphtheria, hosted by the UK’s WHO Collaborating centre for Diphtheria & Streptococcal Infections at the Centre for Infections on 6-8 June 2007.

Further information about DIPNET and a full list of participants can be viewed on the DIPNET website at www.dipnet.org

April 2007

Enhanced surveillance to assess the impact of the pneumococcal conjugate vaccine (PCV) programme for children in England and Wales.

The seven-valent pneumococcal conjugate vaccine (PCV) was added to the routine infant immunisation schedule on 4th September 2006 together with a pneumococcal vaccine catch-up campaign for children aged less than 2 years. In order to monitor the impact of this programme both in the targeted age groups and those not eligible for PCV, the Health Protection Agency through RSIL and the Immunisation Department at CfI and the Vaccine Evaluation Unit and Meningococcus Reference Unit, Manchester Regional HPA laboratory has established a detailed surveillance protocol for England and Wales. All cases of invasive pneumococcal disease (IPD) in children eligible for routine or catch-up PCV immunisation are being actively followed up to obtain vaccination and clinical history in order to advise on the subsequent clinical management of each case and to offer post-vaccination serotype-specific IgG pneumococcal antibody testing. This enhanced surveillance will enable us to identify risk factors for vaccine failure and allow the effectiveness of the PCV schedule in infants and toddlers to be evaluated. The enhanced surveillance will also examine the indirect effects of the PCV vaccination programme on the incidence of serotype-specific IPD in older age/unvaccinated age groups and compare the magnitude of this effect with that of the 23-valent plain pneumococcal polysaccharide (PPV) vaccination programme in the 65+ year olds. To date 312 cases of IPD in children in England and Wales born after 04/09/04 have been reported to CfI and the infecting serotype has been determined for 270 (86.5%), of these 165 (61.1%) had a 7-valent serotype, meningitis occurred in 64 (21%) and 31 (9.9%) are known to have died. Vaccination status is currently known for 297 (95.2%) children and 77 had received one or more doses of PCV before onset. To date there have been 9 vaccine failures, i.e. infection due to a vaccine serotype in children who have received one or more doses of the vaccine; 7 children aged >8 months received a single dose of PCV and 2 children aged

Figure 1. Cumulative weekly number of reports of IPD due to one of the seven serotypes present in pneumococcal conjugate vaccine (PCV) for children aged 0-2 years in England and Wales by Epidemiological year: July-June (2003-date)

Figure 2. Cumulative weekly number of reports of IPD due serotypes not present in pneumococcal conjugate vaccine (PCV) for children aged 0-2 years in England and Wales by Epidemiological year: July-June (2003-date)

 

• Cumulative Weekly Number of Reports of Invasive Pneumococcal Disease Due To One of the Seven Serotypes Present in Prevenar™ for Children Aged 0-2 Years in England and Wales by Epidemiological Year: July-June (2003-Date)
• Cumulative Weekly Number of Reports of Invasive Pneumococcal Disease Due To One of the Serotypes Not Present in Prevenar™ for Children Aged 0-2 Years in England and Wales by Epidemiological Year: July-June (2003-Date)

 

January 2007

Outbreaks of group A streptococcal infection in UK maternity Units

During December 2006 and January 2007, the HPA Respiratory and Systemic Infection laboratory were involved in the investigation of four small outbreaks of superficial wound and also serious infections (blood poisoning) caused by group A streptococci amongst females who had given birth. The infections occurred solely amongst the mothers, none of the babies were infected (1). This bacterium is an uncommon cause of infection following vaginal delivery, and can be carried either in the vagina or in the throat, usually by the mother or even a staff member of the maternity unit.

The outbreaks occurred in different parts of England (West Suffolk, Manchester, Southampton and Truro). Each outbreak was caused by a different type of group A streptococcus (as identified using DNA typing). In one outbreak, the same type was found in the midwife attending one of the patients (she had a sore throat at that time) and in another outbreak, the same type was found in throat samples from the husband and daughter of one of the patients. There was no clear source identified in the other two outbreaks. It is unusual to see these infections amongst females after childbirth; however, this was not the case in the pre-antibiotic era. These infections emphasise the need to screen staff working in these units and also for staff to be made more aware of the potential consequences of declaring these infections and not returning to work until they are clear of the organism. Any healthcare worker found to be positive for these organisms should not be allowed to care for patients until after 24h of antimicrobial treatment.

(1). The group A streptococcus is a bacterium that can be found in the mucous membranes (mouth, respiratory tract, intestine, vagina). Some individuals may be carriers with no symptoms. Common infections caused include acute tonsillitis (sore throat) and skin infections. It can spread through respiratory contact or the air.

August 2006

The Chief Medical Officer has recently announced significant changes to the Childhood Immunisation Programme with the introduction of pneumococcal conjugate vaccine (PCV) for all children from the 4th of September 2006. There will also be a pneumococcal vaccination catch-up campaign for children aged less than two years. In order to monitor the impact of the PCV vaccination programme on the incidence of invasive pneumococcal disease (IPD) caused by the 7 vaccine serotypes, vaccine-related serotypes and non-vaccine serotypes in the age groups targeted by the vaccine, the Centre for Infections through its Immunisation Department, Respiratory and Systemic Infection Laboratory and Meningococcus Reference Unit have set in place a detailed surveillance protocol. In addition to conventional culture based surveillance for IPD, diagnostic PCR and serotype specific antigen detection will be undertaken on all culture negative cases of meningitis and empyema occurring in children in order to maximise the surveillance information obtained. In addition IPD cases occurring in children eligible for routine or catch-up immunisation will be further investigated for risk factors and mechanisms of PCV vaccine failure and to measure the serotype-specific IgG response to a booster dose in these children. in the light of experience in the United States of America, Where PCV immunisation was introduced in 2001 it is anticipated that there will also be significant impacts on invasive pneumococcal disease in age groups not targeted for PCV vaccination. Thus the surveillance also aims to examine the indirect effect of the PCV vaccination programme on the incidence of IPD caused by vaccine and non-vaccine serotypes in older age/ unvaccinated age groups and, in those aged >65 years, and to compare the magnitude of this effect with that of the existing 23-valent plain polysaccharide vaccination (PPV) programme.

April 2006

A novel approach to pneumococcal typing in the reference laboratory using Bio-Plex suspension array technology.

Since December 2005, a novel approach to pneumococcal type determination has been introduced using Bio-Plex suspension array technology for all referred clinical isolates of Streptococcus pneumoniae. This technology has replaced the traditional conventional methods (slide agglutination and capsule swelling reaction) that have been used at Colindale and globally for the last sixty years. The new technology has enabled pneumococcal serotype determination for 13 of the most commonly isolated serotypes (1, 3, 4, 5, 6A, 6B, 7F/A, 9V, 14, Group 18, 19A, 19F and 23F) from a single sample well via a multiplex immunoassay using distinct labelled microspheres conjugated to monoclonal antibodies specific to different serotypes/groups. The assay set also includes a c-polysaccharide assay, which is used as an internal positive control in cases where the serotype of the isolate is not available within the test panel.

The Bio-Plex assay currently allows the semi-automated serotyping of 60-75% of the serotypes commonly observed within England and Wales, with up to a further 10% determined to serogroup level. Any isolates that require subtyping or that do not type with the range of antibody reagents in the Bio-Plex assay are serotyped by conventional slide agglutination. There were 3211 pneumococcal isolate referrals during the period December 2005 to the end of April 2006, and 65%-70% were typed using the Bioplex assay.

The Bio-Plex system provides an unambiguous, controlled and fully traceable numerical result output that lends itself to automatic analysis and uploading into the MOLIS system, thus avoiding some of the pit-falls associated with the subjective nature of conventional serotyping, which requires experience and highly skilled handling for the most accurate results. This is the first application of such technology at Colindale and has demonstrated to be an effective and efficient 21st century tool for reference public health microbiology and epidemiology. Other reference laboratory applications are currently being explored in addition to further streamlining the current system towards automation.

March 2006

Fatal case of diphtheria caused by toxigenic Corynebacterium ulcerans

Joint Divisional Report from HPA Centre for Infections Respiratory and Systemic Infection Laboratory (RSIL) and HPA Centre for Infections Immunisation Department

A toxigenic C ulcerans has been isolated from pharyngeal samples taken from a 76y female with a five-day history of pyrexia, breathing difficulties, 'throat restriction' and cervical lymphadenopathy. The local Health Protection Unit provided support in obtaining diphtheria anti-toxin for the patient, contact tracing, communication with health care staff and family members, and organising antibiotics and vaccine boosters for close contacts. The HPA Centre for Infections Immunisation Department and RSIL provided laboratory testing and advice. Throat swabs and clinical samples from the patient were submitted to RSIL for examination and yielded a diphtheria toxin producing strain of C ulcerans. Contact tracing was undertaken and swabs taken from family contacts and members of hospital staff that had attended the patient were all negative. The patient had visited her daughter's dairy farm prior to developing the illness. In addition, DEFRA and the VLA Preston were informed to undertake milk and animal sampling on the farm. C ulcerans is a documented zoonosis and known to cause mastitis in cattle and respiratory and/or infections in other domestic and wild animals. There were several cows on the farm with sub-clinical symptoms of mastitis (high somatic cell counts in their milk). Companion animal samples were examined by RSIL and toxigenic C ulcerans was isolated from the throat swabs of two pet Alsatians, the other samples taken from various pets were negative for C ulcerans. The VLA and Royal Hospital, Preston examined milk samples taken from cows with mastitis and were also negative. The patient and animal strains are currently being genotyped by RSIL and the DNA patterns will be matched against those stored in the C ulcerans database.

Note:
This is the second death in an elderly patient due to toxigenic C ulcerans; the last death again in an elderly woman occurred in 2000. During the period 2000-2005, 18 cases of toxigenic C ulcerans have been documented in the UK. Most cases had no association with a farming community or the consumption of dairy products. During 2002 - present, the organism has also been isolated from several domestic cats within the UK and one dog in France with respiratory discharges, suggesting a potential novel reservoir for this organism. Molecular typing studies undertaken by RSIL on a large collection of isolates have revealed a 'predominant' genotype present amongst strains from human infections within Europe, with strains isolated from UK domestic cats exhibiting the same predominant type as observed in human infections.

December 2005

Pertussis outbreak in a Primary School

Together with colleagues at the East Midlands HPU, RSIL has been investigating a pertussis outbreak in a primary school in Leicestershire. Following serological confirmation of current/recent pertussis infection in the index case in November 2005, additional sera were obtained from suspected cases who had been symptomatic for several weeks. Three of five patients so far examined have evidence of current/recent pertussis infection. Two siblings of the index case were also symptomatic but they were reluctant to have a blood sample taken. However oral fluid samples were obtained from them and RSIL's newly developed oral fluid antibody assay was used to confirm current/recent pertussis in one of these. This illustrates the usefulness in this non-invasive assay in allowing laboratory confirmation of suspected cases. We anticipate that this assay will be deployed more widely in support of the further enhancements to national pertussis surveillance which are currently being planned with colleagues in the Immunisation Department of CfI and in LARS.

This outbreak investigation follows on from a number of similar incidents over the last few months and highlights the increasing awareness of pertussis infections in children and young adults.

October 2005

Sudden Unexplained Death in Infancy (SUDI)

RSIL and the Immunisation Department of the Centre for Infections have initiated a pilot project to enhance the microbiological diagnostic approaches in investigation of Sudden Unexplained Death in Infancy (SUDI). This follows the report of a working group of The Royal College of Pathologists and The Royal College of Paediatrics and Child Health on Sudden unexpected death in infancy chaired by Baroness Helena Kennedy QC. The Pilot Project is being conducted in collaboration with Professor Peter Fleming, who leads the South West Infant Sleep Scene Study (SWISS) and LaRS. This project seeks to investigate in a standardised way all cases of Sudden and Unexplained Death in Infancy occurring in the South West Region. Samples collected at or near the time of death and at post mortem are being investigated locally and aliquots of all materials referred on to the Centre for Infections, where RSIL acts as the receiving and co-ordinating laboratory. Samples are transferred on to other departments within CfI, particularly the Virus Reference Department for a range of molecular diagnostic investigations as well as being tested for a wide range of bacterial infections by such assays within RSIL. The pilot project officially went live at the beginning of September, and to date two cases have been investigated. It is intended to run the pilot project for approximately one year, and then review the available data in order to determine whether the application of a battery of molecular tests to these materials increases the diagnostic yield in SUDI. This study is in accord with the HPA's Children's Health Initiative.

September 2005

Pertussis

RSIL and the Immunisation Department have been liaising with Health Protection Units in the West Midlands over a possible increase in cases of pertussis. In some of the HPU areas within the West Midlands, notifications have increased significantly in 2005 over previous years. It is not entirely clear at this stage whether this is due to increased ascertainment, as a consequence of the services RSIL is now offering, or whether it is indeed a genuine increase and investigations continue. We have taken this opportunity to remind colleagues of the pertussis diagnostic services offered by RSIL in support of surveillance. These are:

1. serodiagnosis for individuals with a cough of more than 2 weeks duration using a pertussis toxin IgG antibody test
2. a same day PCR service for infants aged less than 6 months, who have been hospitalised with suspect pertussis.
3. standard serotyping of Bordtella pertussis cultures

 

June 2005

Vaccine effectiveness of the Universal Pneumococcal Immunisation Programme

In England and Wales, universal pneumococcal immunisation for the elderly (80 year olds) began in August 2003. The estimated additional coverage by end April 2004 achieved as a result of this universal programme in England was 26%. In April 2004 the programme of universal PPV immunisation was extended to include all individuals aged 75 years and from April 2005 all aged 65 became eligible for the vaccine. A retrospective follow-up of all cases of invasive pneumococcal disease (IPD) occurring in the target age groups is being undertaken by the Respiratory and Systemic Infection laboratory and the Immunisation Department, of the Centre for Infections.

Pneumococcal serotype has been determined for 736/1184 (62%) of IPD cases in those aged over 80 year identified by the Centre for Infections between 04/11/03 and 04/11/04 and to date PPV vaccination status has been determined for 499/736 individuals (68%)

Using data on the proportion of vaccinated cases with a vaccine serotype, the effectiveness of PPV in the 80 year age group has been estimated to be 71% (95%CI 34-78) for those vaccinated within the previous 2 years, falling to 23% and 0% for those vaccinated 2-4 and 5-10 years ago respectively. Based on estimated vaccine coverage in the 80 age group, effectiveness of PPV against IPD using the screening method was conservatively estimated to be 73%(95%CI 63-81) for those vaccinated in the previous 2 years, falling to 41%(20-58) and 13%(-13-33) for those vaccinated 2-4 and 5-10 years ago respectively.

The enhanced surveillance is on-going and data from winter 2004/05 on IPD amongst those aged 75 years is being sought and analysed at present. The full report on vaccine effectiveness in the 80 age group as submitted to the JCVI is now available on the HPA website at JCVI new 2005 (PDF, 84 KB)

 

May 2005

Legionella

RSIL has been involved in the investigation of a case of Legionella pneumonia in a south London teaching hospital. The patient's urine was positive for legionella antigen, serology was positive for L. pneumophila serogroup 1 and L. pneumophila serogroup 1 was isolated from a BAL. Environmental sampling in the intensive care unit identified L. pneumophila serogroup 1 in the hot and cold water supplies. The environmental isolates were of the same Mab type as the isolate from the patient.

Interestingly another patient with legionella infection was treated in the same unit last July. Ther clinical isolate and environmental isolates collected at that time are of the same Mab type as the current isolates.

 

April 2005

Surveillance for Invasive Pneumococcal disease in Hospitalised Children, Khanh Hoa Province, Viet Nam

RSIL is collaborating with the International Vaccine Institute, Seoul, Korea, The National Institute of Hygiene and Epidemiology, Hanoi, Viet Nam and the Khanh Hoa General Hospital, Nha Trang, Viet Nam in this pilot study, which is being funded by the GAVI Pneumococcal ADIP. RSIL 's role is to assist in the capacity-building programme for the bacteriology laboratory in the Nha Trang General Hospital .

Dr Mary Slack visited Nha Trang in February to deliver a short course on the diagnosis of bacterial meningitis and pneumonia and bacteriological techniques for the culture, identification, preservation and transport of Streptococcus pneumoniae and Haemophilus influenzae, and quality assurance/quality control (QA/QC) procedures in Microbiology. RSIL will be organising a proficiency testing programme for the laboratory

 

March 2005

Hib Vaccination Catch-up -the impact of the campaign

After the introduction of Hib vaccine in 1992 a massive decline was observed in cases of invasive Hib infection (figure1) The decline was most marked in the under five year old age group who were targeted for vaccination but was also apparent in unvaccinated age groups (including adults). Since 1999, the number of cases of type b infection started to increase reaching a peak in 2002. The increase was most marked in children under five years of age but also seen in all other age groups including adults.

A Hib vaccination catch-up campaign was conducted by the Department of Health between May 2003 and January 2004, targeting all children aged from 6 months up to 4 years on 1 April 2003. National vaccine coverage for the 6 to 12 month age group was 71.8%. National vaccine coverage for the 13 to 48 months age group was 63.2%.

Following the campaign, the number of cases reported fell in the age groups vaccinated. This reduction is dramatic in the age groups targeted for vaccine but has also been observed in older children and adults. The decline in adults was observed mainly in the final quarter of the year suggesting that further decline in total numbers will be expected during 2005.

 

Figure: Invasive Hib infections by age group, 1990-2004Source: England and Wales, HPA Centre for Infections

There has already been an impact of the campaign leading to a major decrease in the age groups targeted for vaccination. A high incidence continues to be observed in older children and adults but with this has also declined during 2004 to levels similar to 2002. This suggests that, in the same way as occurred after the initial catch-up campaign, older unvaccinated age groups are being offered indirect protection - possibly due to declining rates of carriage.

February 2005

Impact of the Universal Pneumococcal Immunisation Programme for 80 year olds in England and Wales using 23-valent plain pneumococcal polysaccharide vaccine (PPV)

In England and Wales, universal pneumococcal immunisation for the elderly (80 year olds) began in August 2003. The estimated coverage by end April 2004 achieved as a result of this universal programme in England was 26%.

A retrospective follow-up of all cases of invasive pneumococcal disease (IPD) in the 80 age group known to the HPA is being undertaken by the Respiratory and Systemic Infection laboratory and the Immunisation Department of CfI

The incidence of IPD in 80 year olds in England and Wales in the epidemiological year July 2003 to June 2004 was 9% lower than the average annual based on the seven previous epidemiological years. This change compares with an overall increase across all age groups of 4% in 2003/4 compared with the annual average in the previous seven years.

Pneumococcal serotype has been determined for 736/1184 (62%) of IPD cases in 80 year olds identified by the Centre for Infections between 04/11/03 and 04/11/04.To date PPV vaccination status has been determined for 499/736 individuals (68%) Among vaccinated cases, the proportion with a vaccine-preventable serotype increased with time since vaccination, from 79% in those vaccinated in the previous two years, to 91% and 95% in those vaccinated 2-4 and 5-10 years ago respectively.

The vaccine effectiveness in the 80 year age group has been estimated by the screening method to be 73% (95%CI 63-81) for those vaccinated within the previous 2 years, falling to 41% (20-58) and 13% (-13-33) for those vaccinated 2-4 and 5-10 years ago respectively.

There has been no discernible effect of PPV on overall case fatality from IPD in the 80 year age group

A report of these findings was considered by the JCVI at its meeting in February.

Hib Vaccination Catch-up - the impact of the campaign.

The Haemophilus Reference Unit, RSIL and the Immunisation Department of CfI have been conducting enhanced surveillance of invasive Haemophilus influenzae infections since 1990.Following the introduction of Hib vaccine in 1992 a massive decline was observed in cases of invasive Hib infection (figure1) The decline was most marked in the under five year old age group who were targeted for vaccination but was also apparent in unvaccinated age groups (including adults). Since 1999, the number of cases of type b infection started to increase reaching a peak in 2002. The increase was most marked in children under five years of age but also seen in all other age groups including adults.

A Hib vaccination catch-up campaign was conducted by the Department of Health between May 2003 and January 2004, targeting all children aged from 6 months up to 4 years on 1 April 2003. National vaccine coverage for the 6-12 month age group was 71.8%. National vaccine coverage for the 13-48 months age group was 63.2%.

Following the campaign, the number of cases reported fell in the age groups vaccinated. This
reduction is dramatic in the age groups targeted for vaccine but has also been observed in older children and adults. The decline in adults was observed mainly in the final quarter of the year suggesting that further decline in total numbers will be expected during 2005.

There has already been an impact of the campaign leading to a major decrease in the age groups targeted for vaccination. A high incidence continues to be observed in older children and adults but with this has also declined during 2004 to levels similar to 2002. This suggests that, in the same way as occurred after the initial catch-up campaign, older unvaccinated age groups are being offered indirect protection - possibly due to declining rates of carriage.

These findings were presented to the JCVI at its meeting in February.

Surveillance for Invasive Pneumococcal disease in Hospitalised Children , Khanh Hoa Province, Vietnam

RSIL is collaborating with the International Vaccine Institute, Seoul, Korea, The National Institute of Hygiene and Epidemiology, Hanoi, Vietnam and the Khanh Hoa General Hospital, Nha Trang, Vietnam in this pilot study, which is being funded by the GAVI Pneumococcal ADIP.

RSIL's role is to assist in the capacity-building programme for the bacteriology laboratory in the Nha Trang General Hospital.

Dr Mary Slack visited Nha Trang in February to deliver a short course on the diagnosis of bacterial meningitis and pneumonia and bacteriological techniques for the culture, identification, preservation and transport of Streptococcus pneumoniae and Haemophilus influenzae, and quality assurance/quality control (QA/QC) procedures in Microbiology. RSIL will be organising a proficiency testing programme for the laboratory.

 

January 2005

International Symposium
Current Global Perspectives in the Field of Streptococcal and Pneumococcal Infections

An international symposium on streptococcal and pneumococcal infections organised by the HPA Respiratory and Systemic Infection Laboratory, will be held at the Health Protection Agency Centre for Infections, Colindale, London during the period 11-12 April 2005. The symposium is aimed at all healthcare professionals in particular, clinicians, paediatricians, microbiologists, public health specialists, infection control specialists, epidemiologists and anybody that has a professional interest in these infections. A range of topics focusing on clinical, epidemiological and microbiological aspects will be presented by national and international speakers from across the globe, including key experts from the USA, Australia, New Zealand, Europe and South East Asia. The Symposium also coincides with the meeting of the XVI Lancefield International Advisory Committee.

Programme information and registration forms are also available on the Events page of the Health Protection Agency website. The deadline for registration is 11 March 2005.

 

December 2004

Pertussis in a neonatal intensive care unit

This month RSIL provided extensive laboratory support to colleagues in a large London hospital and the local HPU who were investigating a case of nosocomially-acquired pertussis in their neonatal intensive care unit (NICU). The investigation was undertaken against a background of unusually high numbers of reports of pertussis in the locality. In an attempt to avoid a cross infection problem in the NICU and also to track the source of the infection, all 28 babies in the NICU were tested by PCR. Apart from the index case no patient had evidence of infection. As RSIL use a real-time PCR we were able to provide results to the hospital on the day of specimen receipt and thus to reassure the hospital that there were no unrecognised cases of pertussis on the Unit.

Subsequently, while culture was undertaken locally, RSIL provided serological testing for 19 staff and other adult contacts of the NICU. Evidence of recent infection (high levels of antibody against B.pertussis toxin) was found in one contact who had a history of prolonged cough. Investigations are on going.

November 2004

RSIL Newsletter

RSIL produced a newsletter, which has been distributed to all of RSIL's users and can be viewed by clicking " Newsletter".
It is the first issue of an occasional newsletter and describes some of RSIL' s recent activities and current projects.

Items highlighted included:

· Relocation of the Haemophilus Reference Unit

· Legionella pneumophila incidents

· Bartonella infections in Great Britain

· Strep-EURO: Severe Streptococcus pyogenes infections in Europe

· Enhanced surveillance to support universal pneumococcal immunisation in the elderly

 

October 2004

Group A streptococcal (GAS) skin infections amongst abattoir workers in Carmarthen

Fourteen cases of GAS superficial skin infections amongst abattoir workers have been reported from West Wales. Extensive environmental and contact swabbing was undertaken. An outbreak control team was established as a consequence. Most cases occurred on the slaughter line (lamb line) and it appeared that person-to-person spread had occurred with the carcass being the vector of carriage. GAS isolates (all tetracycline resistant) were submitted to the Streptococcus and Diphtheria Reference Unit (SDRU) for typing. All were non-typable by classic serotyping and emm sequence-based typing revealed a type rarely seen within the UK and Europe, emm 108.1 However, this type has been identified in other areas of the world, for example, Malaysia and South America and is associated with skin infection.

The risk to humans through the food chain is very low, although previous outbreaks had reported transmission in meat handlers remote from the site. No further cases observed as of this time.

Relocation of Haemophilus Reference Unit

On 1st November 2004 the HPA Haemophilus Reference Unit (HRU) relocated to The Centre for Infections to join the main body of the Respiratory and Systemic Infection Laboratory in Colindale. This will not affect the service provided by the HRU. The HRU will continue to work closely with the Communicable Disease Surveillance Centre (CDSC) and the Oxford Vaccine Group (OVG) in conducting collaborative activities on Haemophilus influenzae and assessing the impact of Hib vaccine. The HPA HRU and CDSC will continue to conduct high quality surveillance in order to fully assess the impact of the recent Hib booster campaign.

September 2004

Legionella outbreaks

RSIL has been heavily involved in legionella outbreak investigations this month. During September we have supported investigations into eight clusters/outbreaks spread across England. Prompt referral to RSIL of Legionella pneumophila antigen positive urine samples has led to the rapid confirmation of these incidents and allowed us to obtain suitable respiratory samples for culture and isolation. Consequently we have obtained an unprecedented number of culture isolates and have been able to undertake monoclonal antibody (mAb) subgrouping and DNA sequence based typing (SBT) for most incidents.

Although some investigations are still ongoing in most of these clusters it has been concluded that either the patients were infected by different strains (distinct mAb and/or SBT profiles) or, although a single strain was involved, there was no obvious epidemiological link between the cases and no confirmed source of infection has been identified to date.

At this time it is not clear whether we are seeing a genuine increase in incidence of legionellosis or rather an improvement in ascertainment due to heightened awareness.

Relocation of Haemophilus Reference Unit to RSIL

The Health Protection Agency Haemophilus Reference Unit (HRU), in collaboration with CDSC and the Oxford Vaccine Group (OVG) has been surveying all cases of invasive Haemophilus influenzae disease in England and Wales since 1995. This on-going survey provided evidence of a resurgence of cases of invasive H. influenzae disease in children and adults. As a result of this the Department of Health implemented a booster campaign in 2003 whereby children over 6 months and less than 4 years of age were offered an extra dose of Hib vaccine. Coverage in the campaign was high and it had a marked effect on the incidence of invasive Hib disease in 1-4 year olds, with an 87% reduction in the number of cases in this age group in the first 6 months of 2004. The incidence in older children and adults has fallen by 25% over the same period.

From 1 November 2004 the HPA Haemophilus Reference Unit will be located within the Respiratory and Systemic Infection Laboratory of the Central Public Health Laboratory in Colindale. This will not affect the service provided by the HRU. The HRU will continue to work closely with CDSC and OVG in conducting collaborative activities on Haemophilus influenzae and assessing the impact of Hib vaccine. It is of vital importance that this high quality surveillance continues in order to fully assess the effect of the recent Hib booster campaign.

 

August 2004

Strep-EURO: Severe streptococcus pyogenes infections in Europe

Strep-EURO is an EU FP-5 funded programme (led by Lund University, Sweden) designed to enhance our understanding of severe group A streptococcal (GAS) infections. The HPA Respiratory and Systemic Infection Laboratory (RSIL, SRMD) in collaboration with the HPA Healthcare Associated Infections and Antimicrobial Resistance Department (HCAI, CDSC) are the official UK contractors within this programme. The second year periodic report from RSIL/HCAI has now been submitted.

Enhanced population-based surveillance was implemented in the UK in part fulfilment of the strep-EURO objectives. Two pre-existing HPA data sources were reconciled to maximise case ascertainment:: namely routine national surveillance (LabBase) and isolate referrals to RSIL. Individual cases were followed-up to capture clinical and epidemiological information. Preliminary data relating to cases diagnosed in 2003 have this far been analysed to determine the burden, clinical presentation and risk factors for disease, and microbiological characteristics of strains.

Two hundred and twenty-threelaboratories reported a total of 2064 cases across England and Wales, an overall incidence of 3.93 per 100,000 population. A clear seasonal pattern was apparent, with peak incidence from mid-March to mid-April. The observed incidence in males was higher than in females. Twelve per cent of cases occurred in children (and less than 18 years). Ninety per cent of cases were bacteraemic, 10% had septic arthritis and 9% pneumonia. Other clinical manifestations included toxic shock-like syndrome (6%), necrotising fasciitis (5%), puerperal sepsis (3%) and meningitis (1%). Skin lesions/wounds were the most common predisposing factor, with injecting drug use reported in 30% of cases; 28% had no predisposing/risk factors identified. Nineteen per cent of cases were reported as having died within seven days of diagnosis. Local microbiological analysis identified 4% of GAS isolates as erythromycin resistant. Type characterisation of strains using a combination of serological and emm sequencing revealed over 35 M-types, with M1, M3 and M87most common.

The surveillance has succeeded in improving our estimates of the incidences of these infections and comparison with the other ten participating European countries will further our understanding of these data.

 

July 2004

Outbreak of invasive pneumococcal disease in a Nursery

RSIL are assisting the local Health Protection Unit and laboratory in the investigation of an outbreak of invasive pneumococcal disease in a nursery in Norfolk. Three children aged less than 6 months developed invasive pneumococcal disease over a 3-month period. All three cases were caused by an erythromycin resistant serotype 14 strain of Streptococcus pneumoniae. Following advice given by RSIL and CDSC's Immunisation Department rifampicin chemoprophylaxis was administered and all of the children aged S.pneumoniae. Another 18 children were carrying other serotypes of pneumococcus. None of the adults were carrying pneumococci. The invasive and carriage isolates of serotype 14 are being further characterised by MLST.

Unexplained infection in a Bone Marrow Transplant Unit

RSIL and ERNVL are assisting the local Health Protection Unit and laboratory in the investigation of 5 cases of unexplained severe respiratory infection in children who have undergone bone marrow transplantation in the West Midlands. The Unexplained Infection Protocol was instituted for the investigation of these cases. RSIL has undertaken molecular testing for S. pneumoniae, M. pneumoniae, C. pneumoniae, B. pertussis, L. pneumophila and M. amphoriforme. All of these tests have been negative. To date whilst possible causes of the respiratory tract infection have been noted in some of the children, no single cause has been shown to be responsible. Microbiological investigations are continuing and various samples are now undergoing 16S PCR within the Genomics Proteomics and Bioinformatics Unit of SRMD.

 

June 2004

Pertussis

RSIL are assisting local Health Protection Units and laboratories in the investigation of a number of outbreaks of pertussis in primary schools in Leicestershire, Derbyshire and Oxfordshire. The cases are predominantly children who are too old to have received the pre-school booster of pertussis, i.e. >8y. Pertussis infection has been confirmed by serology and in some cases by culture and/or PCR.

Enhanced surveillance to support universal pneumococcal immunisation in the elderly

In May 2002 the JCVI recommended that 23-valent plain pneumococcal vaccine (PPV) should be offered to all individuals aged 65 y and over. The programme commenced in August 2003 when PPV was offered to all individuals aged 80y and over. In April 2004 PPV was offered to all 75 y olds and from April 2005 PPV will be offered to all 65 year olds. To support this programme an enhanced surveillance scheme has been developed by RSIL and CDSC.

• Retrospective follow-up of all cases of invasive pneumococcal disease (IPD) in the 80 age group known to the HPA was undertaken from 04.11.03. From 04.11.03-01.04.04 671 cases of IPD in this age group have been followed up.
• 402/671 (60%) of pneumococcal isolates have been serotyped by RSIL. 91% of serotyped isolates are included in PPV.
• As of 15.06.04 we had received responses from the GP for 197 patients, giving details of PPV immunisation history, clinical details and outcome. 80/197 (48%) of these patients have been immunised with PPV. The mortality in the 80 y age group is high (45% in those immunised with PPV and 49% in those not immunised with PPV)
• The surveillance is continuing as the PPV programme is expanded to cover 75 and 65 year old age groups. The workload of the surveillance is expected top double over the next 2 years.

Legionella

The usual seasonal increase in cases of legionellosis is being observed in specimens referred to RSIL.

 

May 2004

Group A Streptococci

As part of the on-going investigations into the recent increase in invasive Group A streptococcal disease RSIL has typed all of the non-invasive Group A streptococcal isolates submitted to two Microbiology laboratories in South Yorkshire and one laboratory in North London over a 6-week period. Overall 22 different M-types were noted amongst 144 non-sterile site isolates (101 from throat swabs) from Yorkshire and 78 non-sterile site isolates from the laboratory in London. There was no predominant M type and the M-types causing invasive disease were similar to those associated with non-invasive disease. As yet there is no meaningful explanation of the recent increase in GAS infections.

Sudden unexplained deaths in infancy (SUDI)

The protocol for investigation of SUDI is nearing completion. RSIL is acting as the lead laboratory, providing advice on referral of specimens, receiving specimens collected at the time of death and at post mortem and coordinating the collection and transport of relevant specimens to appropriate reference laboratories within the SRMD of the HPA.

Update on Hib Booster campaign ( HRU/CDSC data):
The Hib booster campaign began in May 2003 and has now been completed. An extra dose of Hib vaccine was offered to all children born after 1 January 2000. Coverage in the campaign was high, though lower than in other campaigns in this age group.

The number of cases of confirmed Hib disease for the first 17 weeks of 2004 has been compared to the number for the same period in 2003. There has been an overall reduction of 43%: an 87% reduction occurred in 1-4 year olds with no overall change in those above the age targeted for vaccine. The reduction in children aged

 

April 2004

Bartonella infections in Great Britain

In preparation for a presentation at the ESCMID meeting in Prague, RSIL has re-analysed the microbiological and demographic data obtained during seven years of routine laboratory testing. RSIL provides diagnostic service for estimation of bartonella antibodies using Focus Bartonella IFA IgM and IgG. RSIL also tests biopsy material from seropositive cases by PCR for bartonella DNA.

Since January 1997, 10,507 samples have been submitted to RSIL for investigation of possible "bartonellosis". 1,759 (16.7%) had evidence of infection: 9.0% had evidence of recent/current infection, 7.0% infection at an indeterminate time and 0.7% past infection. The rate of infection was highest in children aged 0-9y (20.1% of cases).

The clinical presentations of the first 1000 consecutive patients with positive serology were analysed. There were 449 cases of Cat Scratch Disease, 56 cases of Bartonella endocarditis, 19 PUO and 3 cases of bacillary angiomatosis. In 433 cases insufficient clinical details were given. PCR of excised heart valves confirmed B.henselae, B.quintana and B.vinsonii as causative agent of endocarditis.

Bartonella spp. are a major cause of zoonotic infection in Great Britain. Bartonella should be considered as possible aetiology of Infective Endocarditis. Serology provides an excellent and cost-effective approach to diagnosis of bartonellosis.

 

March 2004

Group A Streptococci

• RSIL is investigating a number of interesting clusters of GAS infection.
  
• An outbreak of skin sepsis at a Marine Camp in Devon. This condition has been previously described as "Woodbury Rash". There have been 25 isolates of GAS, M-59 associated with skin sepsis from this location. M-59 is a known nephritogenic type, which is uncommon in the UK. It is more frequently found in the West Indies.
  
• An increased number of isolates of GAS M-18 in the southern part of the Yorkshire and Humberside Region. This GAS serotype has been rarely isolated in the UK in recent years. These have included 3 cases of necrotising fasciitis and 2 fatal cases of septicaemia. Many of the M-18 isolates have been mucoid, which is of concern since there is a strong association between mucoid M-18 and rheumatic fever. The Microbiology laboratories of both hospitals in one city of the Region have noticed a significant increase in GAS isolates from primary care, following an alert from the local CCDC regarding the cases of invasive GAS disease. These two laboratories are submitting all their GAS isolates to RSIL over a 2-3 week period in order to provide a snapshot of the M-type distribution of GAS in a city which is experiencing an increase in Mucoid M-18 disease. In March RSIL received 11 M-18 isolates from this city, 5 of which were from blood cultures. Further molecular typing will be performed on the collection of M-18 isolates, but published data to date indicates that these strains are highly clonal. There have also been a smaller number of similar M-18 cases in the adjacent North East Region. RSIL has been providing regular updates of GAS type distribution of isolates submitted from hospitals in their Region to both the Regional HPA offices.
  
• There have been a number of school outbreaks of scarlet fever in South West London and in Frimley.

Tetanus In Injecting Drug Users RSIL continues to be closely involved with the investigation of cases of tetanus in injecting drug users. To date there have been 22 cases of tetanus in this group. The cases have been confined to England. The Netherlands have now reported one case of tetanus in an IDU.

Last reviewed: 17 March 2009