Sarah Collins

Rapid Declines in Age Group–Specific Rotavirus Infection and Acute Gastroenteritis Among Vaccinated and Unvaccinated Individuals Within 1 Year of Rotavirus Vaccine Introduction in England and Wales

BACKGROUND The oral infant rotavirus vaccine, Rotarix, was introduced in England and Wales in July 2013. We estimated the impact on laboratory-confirmed rotavirus infections and hospitalizations for all-cause acute gastroenteritis (AGE) during the first year after introduction. METHODS We extracted data on laboratory-confirmed rotavirus infections (July 2000 through June 2015) and all-cause AGE-associated hospitalizations (July 2007 through June 2014) for all age groups using national databases (LabBase2 and HES). We determined the ratio of the rate during the 2013-2014 rotavirus season to the rate during the prevaccination era. RESULTS In infants, there was a 77% decline (rate ratio [RR], 0.23; 95% confidence interval [CI], .16-.32) in laboratory-confirmed rotavirus infections and a 26% decline (RR, 0.74; 95% CI, .65-.84) in all-cause AGE-associated hospitalizations in 2013-2014, compared with the prevaccination era. Large reductions were also observed in older children, adults, and older adults. We estimated that 10 884 laboratory-confirmed infections and 50 427 all-cause AGE-associated hospital admissions were averted in 2013-2014. Similar reductions have been observed for laboratory-confirmed rotavirus infections during the 2014-2015 season. CONCLUSIONS The rapid declines in rotavirus infection and AGE in vaccinated and unvaccinated age groups within 1 year of introducing an infant rotavirus vaccination program are far greater than expected and than previously reported by other countries.

Invasive Haemophilus influenzae Serotype e and f Disease, England and Wales

Incidence of serotype e was 3-fold lower than serotype f, but it caused more severe clinical disease.

Invasive Haemophilus influenzae Type b Disease in England and Wales: Who Is at Risk After 2 Decades of Routine Childhood Vaccination?

BACKGROUND The introduction of the Haemophilus influenzae serotype b (Hib) conjugate vaccine into national immunization has led to rapid and sustained declines in invasive Hib disease incidence across all age groups. In industrialized countries with established Hib vaccination programs, however, little is known about individuals who develop invasive Hib disease. This study describes the epidemiology of invasive Hib disease in England and Wales during 2000-2012 and the clinical characteristics of laboratory-confirmed Hib cases diagnosed during 2009-2012. METHODS Public Health England (PHE) conducts enhanced national surveillance of invasive Hib disease in England and Wales. Detailed clinical information was obtained for all laboratory-confirmed Hib cases diagnosed during 2009-2012. RESULTS Invasive Hib disease in England and Wales has been declining since 2002, reaching its lowest incidence of 0.02 per 100 000 (14 cases) in 2012. In children aged <5 years of age, Hib incidence was 0.06 per 100 000 (2 cases), compared with 35.5 per 100 000 prior to routine Hib vaccination. Follow-up of all 106 case patients over the 4-year period revealed that most cases occurred in adults (73%) who often had preexisting medical conditions (77%) and presented with pneumonia (56%). The Hib-associated case fatality rate was 9.4% (10/106 cases). CONCLUSIONS Control of Hib disease in England and Wales is currently the best that has been achieved since the introduction of routine Hib vaccination in 1992. Invasive Hib disease is no longer a major cause of acute bacterial meningitis in children but, instead, cases are more likely to present as pneumonia in older adults with comorbidities, similar to the less virulent nonencapsulated H. influenzae.

Risk of Invasive Haemophilus influenzae Infection During Pregnancy and Association With Adverse Fetal Outcomes

IMPORTANCE Unencapsulated Haemophilus influenzae frequently causes noninvasive upper respiratory tract infections in children but can also cause invasive disease, especially in older adults. A number of studies have reported an increased incidence in neonates and suggested that pregnant women may have an increased susceptibility to invasive unencapsulated H. influenzae disease. OBJECTIVE To describe the epidemiology, clinical characteristics, and outcomes of invasive H. influenzae disease in women of reproductive age during a 4-year period. DESIGN, SETTING, AND PARTICIPANTS Public Health England conducts enhanced national surveillance of invasive H. influenzae disease in England and Wales. Clinical questionnaires were sent prospectively to general practitioners caring for all women aged 15 to 44 years with laboratory-confirmed invasive H. influenzae disease during 2009-2012, encompassing 45,215,800 woman-years of follow-up. The final outcome was assessed in June 2013. EXPOSURES Invasive H. influenzae disease confirmed by positive culture from a normally sterile site. MAIN OUTCOMES AND MEASURES The primary outcome was H. influenzae infection and the secondary outcomes were pregnancy-related outcomes. RESULTS In total, 171 women had laboratory-confirmed invasive H. influenzae infection, which included 144 (84.2%; 95% CI, 77.9%-89.3%) with unencapsulated, 11 (6.4%; 95% CI, 3.3%-11.2%) with serotype b, and 16 (9.4%; 95% CI, 5.4%-14.7%) with other encapsulated serotypes. Questionnaire response rate was 100%. Overall, 75 of 171 women (43.9%; 95% CI, 36.3%-51.6%) were pregnant at the time of infection, most of whom were previously healthy and presented with unencapsulated H. influenzae bacteremia. The incidence rate of invasive unencapsulated H. influenzae disease was 17.2 (95% CI, 12.2-24.1; P < .001) times greater among pregnant women (2.98/100,000 woman-years) compared with nonpregnant women (0.17/100,000 woman-years). Unencapsulated H. influenzae infection during the first 24 weeks of pregnancy was associated with fetal loss (44/47; 93.6% [95% CI, 82.5%-98.7%]) and extremely premature birth (3/47; 6.4% [95% CI, 1.3%-17.5%]). Unencapsulated H. influenzae infection during the second half of pregnancy was associated with premature birth in 8 of 28 cases (28.6%; 95% CI, 13.2%-48.7%) and stillbirth in 2 of 28 cases (7.1%; 95% CI, 0.9%-23.5%). The incidence rate ratio for pregnancy loss was 2.91 (95% CI, 2.13-3.88) for all serotypes of H. influenzae and 2.90 (95% CI, 2.11-3.89) for unencapsulated H. influenzae compared with the background rate for pregnant women. CONCLUSIONS AND RELEVANCE Among women in England and Wales, pregnancy was associated with a greater risk of invasive H. influenzae infection. These infections were associated with poor pregnancy outcomes.

Molecular and Epidemiological Review of Toxigenic Diphtheria Infections in England between 2007 and 2013

ABSTRACT Human infections caused by toxigenic corynebacteria occur sporadically across Europe. In this report, we undertook the epidemiological and molecular characterization of all toxigenic corynebacterium strains isolated in England between January 2007 and December 2013. Epidemiological aspects include case demographics, risk factors, clinical presentation, treatment, and outcome. Molecular characterization was performed using multilocus sequence typing (MLST) alongside traditional phenotypic methods. In total, there were 20 cases of toxigenic corynebacteria; 12 (60.0%) were caused by Corynebacterium ulcerans, where animal contact was the predominant risk factor. The remaining eight (40.0%) were caused by Corynebacterium diphtheriae strains; six were biovar mitis, which were associated with recent travel abroad. Adults 45 years and older were particularly affected (55.0%; 11/20), and typical symptoms included sore throat and fever. Respiratory diphtheria with the absence of a pharyngeal membrane was the most common presentation (50.0%; 10/20). None of the eight C. diphtheriae cases were fully immunized. Diphtheria antitoxin was issued in two (9.5%) cases; both survived. Two (9.5%) cases died, one due to a C. diphtheriae infection and one due to C. ulcerans. MLST demonstrated that the majority (87.5%; 7/8) of C. diphtheriae strains represented new sequence types (STs). By adapting several primer sequences, the MLST genes in C. ulcerans were also amplified, thereby providing the basis for extension of the MLST scheme, which is currently restricted to C. diphtheriae. Despite high population immunity, occasional toxigenic corynebacterium strains are identified in England and continued surveillance is required.

Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study

BACKGROUND Pneumococcal conjugate vaccines (PCVs) have substantially reduced the incidence of invasive pneumococcal disease caused by vaccine serotypes; however, replacement disease with non-PCV serotypes remains a concern. We describe the population effect of the seven-valent and 13-valent PCVs (PCV7 and PCV13) on invasive pneumococcal disease in England and Wales. METHODS Using national invasive pneumococcal disease surveillance data for 2016/17, we compared incidence rate ratios (IRRs) against pre-PCV13 (2008/09-2009/10) and pre-PCV7 (2000/01-2005/06) baselines. We also estimated the number of invasive pneumococcal disease cases prevented since the introduction of PCVs. FINDINGS In 2016/17, overall invasive pneumococcal disease incidence (9·87 cases per 100 000; 5450 cases) across all age groups was 37% lower (IRR 0·63, 95% CI 0·60-0·65) than pre-PCV7 incidence (14·79 per 100 000; 8167 cases) and 7% lower (0·93; 0·89-0·97) than pre-PCV13 incidence (10·13 per 100 000; 5595 cases). By 2016/17, PCV7-type invasive pneumococcal disease incidence across all age groups had decreased by 97% (0·24 per 100 000; 0·03, 0·02-0·04) compared with the pre-PCV7 period, whereas additional PCV13-type invasive pneumococcal disease decreased by 64% (1·66 per 100 000; 0·36, 0·32-0·40) since the introduction of PCV13. Invasive pneumococcal disease incidence due to non-PCV13 serotypes doubled (7·97 per 100 000; 1·97, 1·86-2·09) since the introduction of PCV7, and accelerated since 2013/14-especially serotypes 8, 12F, and 9N, which were responsible for more than 40% of invasive pneumococcal disease cases by 2016/17. Invasive pneumococcal disease incidence in children younger than 5 years remained stable since 2013/14, with nearly all replacement disease occurring in adults. We estimated 38 366 invasive pneumococcal disease cases were prevented in the 11 years since the introduction of PCV7. INTERPRETATION Both PCV7 and PCV13 have had a major effect in reducing the burden of invasive pneumococcal disease in England and Wales; however, rapid increases in some non-PCV13 serotypes are compromising the benefits of the programme. FUNDING Public Health England.

Molecular epidemiology of newly acquired hepatitis C infections in England 2008–2011: Genotype, phylogeny and mutation analysis

BACKGROUND Analysis of laboratory testing data collected through the Sentinel Surveillance programme has provided a method for identifying individuals who have recently acquired their hepatitis C virus (HCV) infection. Access to samples from these individuals provided a rare opportunity to undertake molecular characterization studies. OBJECTIVES To describe the epidemiology and genetic diversity of hepatitis C in recent seroconverter infections and to predict how this will impact on HCV treatment and control. STUDY DESIGN One hundred and forty seven samples were available from individuals, identified to have recently acquired their HCV infection. Genotype determination with additional phylogenetic analysis was carried out on NS5B sequences. Analysis across the NS3 region investigated the presence of antiviral resistance mutations. Where possible, molecular data was linked to demographic and risk/behavioural factor information. RESULTS The majority of new infections occurred in males with a mean age of 37 years. The most commonly observed genotypes were 1a (49%) and 3a (42%) and injecting drug use (58%) was the most common risk factor. Genotype distribution differed between persons who inject drugs and those with other risk factors suggesting two possible epidemics. Phylogenetic analysis indicated possible transmission networks within specific risk groups. Amino acid changes associated with antiviral resistance were noted in the NS3 region in some samples. CONCLUSIONS Continued surveillance of linked molecular, virological, demographic and epidemiological information on recently acquired infections will contribute to understanding the on-going HCV epidemic in England.

The importance of tetanus risk assessment during wound management

Public Health England undertakes surveillance of vaccine preventable diseases including enhanced surveillance of clinically suspected tetanus. In the United Kingdom, tetanus has become increasingly rare due to the success of the national routine immunization program. Consequently, few practitioners have experience of diagnosing and managing patients with clinical tetanus. We report two cases of tetanus where comparatively minor wounds proved fatal. These cases highlight the importance of the accurate identification and management of tetanus prone wounds and the fatal consequences from untreated injuries in susceptible individuals. We conclude that appropriate risk assessment for tetanus prophylaxis forms an essential part of wound management.

Using surveillance data to determine treatment rates and outcomes for patients with chronic hepatitis C virus infection

The aim of this work was to develop and validate an algorithm to monitor rates of, and response to, treatment of patients infected with hepatitis C virus (HCV) across England using routine laboratory HCV RNA testing data. HCV testing activity between January 2002 and December 2011 was extracted from the local laboratory information systems of a sentinel network of 23 laboratories across England. An algorithm based on frequency of HCV RNA testing within a defined time period was designed to identify treated patients. Validation of the algorithm was undertaken for one center by comparison with treatment data recorded in a clinical database managed by the Trent HCV Study Group. In total, 267,887 HCV RNA test results from 100,640 individuals were extracted. Of these, 78.9% (79,360) tested positive for viral RNA, indicating an active infection, 20.8% (16,538) of whom had a repeat pattern of HCV RNA testing suggestive of treatment monitoring. Annual numbers of individuals treated increased rapidly from 468 in 2002 to 3,295 in 2009, but decreased to 3,110 in 2010. Approximately two thirds (63.3%; 10,468) of those treated had results consistent with a sustained virological response, including 55.3% and 67.1% of those with a genotype 1 and non‐1 virus, respectively. Validation against the Trent clinical database demonstrated that the algorithm was 95% sensitive and 93% specific in detecting treatment and 100% sensitive and 93% specific for detecting treatment outcome. Conclusions: Laboratory testing activity, collected through a sentinel surveillance program, has enabled the first country‐wide analysis of treatment and response among HCV‐infected individuals. Our approach provides a sensitive, robust, and sustainable method for monitoring service provision across England. (Hepatology 2014;59:1343‐1350)

Risk of Invasive Pneumococcal Disease in Children with Sickle Cell Disease in England: A National Observational Cohort Study, 2010–2015

Objective To describe the clinical presentation, risk factors, serotype distribution and outcomes of invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in the UK. Design Prospective national newborn screening for SCD and enhanced national IPD surveillance. Participants Children with SCD born in England between 1 September 2010 and 31 August 2014 who developed laboratory-confirmed IPD by 31 December 2015. Main outcomes and measures Risk of IPD in children with SCD compared with children without SCD during the surveillance period. Results Eleven children homozygote for haemoglobin S (HbSS) and one double heterozygote for haemoglobin S and C (HbSC) developed IPD. Septicaemia (n=7) and lower respiratory tract infection (n=4) were the main clinical presentations, and serogroup 15 (not present in PCV13) was responsible for 73% (8/11) of cases. Three children with HbSS (27%) died compared with <5% nationally. Children with HbSS had a 49-fold (95% CI 27 to 89, P<0.001) higher risk of IPD compared with their peers without SCD. Conclusions Children with SCD remain at increased risk of IPD despite national newborn screening, early penicillin prophylaxis and high pneumococcal vaccine uptake. They are also more likely to die of their infection compared with their peers without SCD. Most IPD cases are now due to serotypes not covered by PCV13. Healthcare professionals need to work more closely with families with SCD and local communities to emphasise the importance of penicillin prophylaxis, explore barriers, allay misguided beliefs and facilitate rapid access to healthcare.