ORCID Profile
0000-0002-7134-499X
Current Organisation
University of Cambridge
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Publisher: BMJ
Date: 16-09-2004
Publisher: Oxford University Press (OUP)
Date: 07-2016
Abstract: Soil transmitted helminths (STH) continue to be associated with high burdens of disease, with an estimated 1.45 billion people infected with STH globally. The promotion and construction of latrines is considered the first barrier to prevent transmission of STH. The absence of a reliable method to extract STH ova from soil makes it challenging to examine whether the use of latrines may or may not have an effect on environmental contamination with ova. The present study evaluated the recovery rate of a method developed to extract STH ova from soil. The adapted centrifugation and flotation technique was applied to 15 soil types, which were seeded with Ascaris suum ova. Soil type, soil moisture content, soil texture and organic matter content were assessed for each soil s le. The average ova recovery rate was 28.2%, with the recovery rate of the method decreasing with increasing soil moisture content, particle size and organic matter content. The association between recovery rate and organic matter content was statistically significant. The present study identified a low recovery rate for an adapted centrifugation-flotation method, although this was similar to the recovery rate demonstrated by other methods developed for soil. Soil organic matter content was significantly associated with ova recovery rates.
Publisher: European Respiratory Society (ERS)
Date: 20-12-2012
DOI: 10.1183/09031936.00144712
Abstract: Serotypes 1, 3, 7F and 19A are implicated in childhood pneumococcal para-pneumonic effusion (PPE). It is not known whether the same is true for adult PPE. A prospective cohort study was conducted over a 2-year period. Consecutive adults admitted with community-acquired pneumonia (CAP) were studied. Pneumococcal serotype was identified from urine s les using a multiplex immunoassay. Of 920 patients recruited, 366 had pneumococcal CAP 100 of these had PPE and a serotype was determined in 73 patients. Factors associated with PPE were age, pneumonia severity index score and serotype. Serotypes most associated with PPE were 1 (18 (45%) out of 40), 19A (9 (45%) out of 20) and 3 (8 (40%) out of 20). Serotypes common in childhood PPE were independently associated with adult PPE (adjusted OR 2.3 p = 0.003). Serotypes not included in the 7-valent pneumococcal conjugate vaccine (PCV) were more likely to be associated with PPE (OR 2.1 p = 0.024) compared with those in the vaccine. Serotypes included in PCV-13 were as likely to be associated with PPE as those that are not (OR 0.8 p = 0.301). Serotypes 1, 3, 7F and 19A are independently associated with adult PPE, a similar finding to childhood PPE. Serotype replacement following pneumococcal vaccine implementation may influence the spectrum of clinical disease.
Publisher: BMJ
Date: 10-2019
DOI: 10.1136/BMJOPEN-2020-037358
Abstract: Capsular group B Neisseria meningitidis (MenB) is the most common cause of invasive meningococcal disease (IMD) in many parts of the world. A MenB vaccine directed against the polysaccharide capsule remains elusive due to poor immunogenicity and safety concerns. The vaccines licensed for the prevention of MenB disease, 4CMenB (Bexsero) and MenB-fHbp (Trumenba), are serogroup B ‘substitute’ vaccines, comprised of subcapsular proteins and are designed to provide protection against most MenB disease-causing strains. In many high-income countries, such as the UK, adolescents are at increased risk of IMD and have the highest rates of meningococcal carriage. Beginning in the late 1990s, immunisation of this age group with the meningococcal group C conjugate vaccine reduced asymptomatic carriage and disrupted transmission of this organism, resulting in lower group C IMD incidence across all age groups. Whether vaccinating teenagers with the novel ‘MenB’ protein-based vaccines will prevent acquisition or reduce duration of carriage and generate herd protection was unknown at the time of vaccine introduction and could not be inferred from the effects of the conjugate vaccines. 4CMenB and MenB-fHbp may also impact on non-MenB disease-causing capsular groups as well as commensal Neisseria spp. This study will evaluate the impact of vaccination with 4CMenB or MenB-fHbp on oropharyngeal carriage of pathogenic meningococci in teenagers, and consequently the potential for these vaccines to provide broad community protection against MenB disease. The ‘Be on the TEAM’ (Teenagers Against Meningitis) Study is a pragmatic, partially randomised controlled trial of 24 000 students aged 16–19 years in their penultimate year of secondary school across the UK with regional allocation to a 0+6 month schedule of 4CMenB or MenB-fHbp or to a control group. Culture-confirmed oropharyngeal carriage will be assessed at baseline and at 12 months, following which the control group will be eligible for 4CMenB vaccination. The primary outcome is the carriage prevalence of potentially pathogenic meningococci (defined as those with genogroups B, C, W, Y or X), in each vaccine group compared separately to the control group at 12 months post-enrolment, that is, 12 months after the first vaccine dose and 6 months after the second vaccine dose. Secondary outcomes include impact on carriage of: genogroup B meningococci hyperinvasive meningococci all meningococci those meningococci expressing vaccine antigens and other Neisseria spp. A s le size of 8000 in each arm will provide 80% power to detect a 30% reduction in meningococcal carriage, assuming genogroup B, C, W, Y or X meningococci carriage of 3.43%, a design effect of 1.5, a retention rate of 80% and a significance level of 0.05. Study results will be available in 2021 and will inform the UK and international immunisation policy and future vaccine development. This study is approved by the National Health Service South Central Research Ethics Committee (18/SC/0055) the UK Health Research Authority (IRAS ID 239091) and the UK Medicines and Healthcare products Regulatory Agency. Publications arising from this study will be submitted to peer-reviewed journals. Study results will be disseminated in public forums, online, presented at local and international conferences and made available to the participating schools. ISRCTN75858406 Pre-results, EudraCT 2017-004609-42.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.JINF.2009.12.008
Abstract: To describe the epidemiology of invasive pneumococcal disease (IPD) in England & Wales in the pre-conjugate vaccine era. We analysed reports of culture-confirmed IPD submitted to the national surveillance system between July 1996 and June 2006. The incidence of IPD was 10 per 100,000 overall, and increased over time. The typical pattern of IPD by age was observed, with the highest incidence in young children and older adults. There was little change in IPD incidence in the elderly, despite the widespread use of 23-valent pneumococcal polysaccharide vaccines since 2003. The distribution of serotypes changed over time notably the proportion of cases caused by serotype 14 decreased, and the proportion due to serotype 1 increased. The incidence of meningitis was 0.6 per 100,000 overall, and as a proportion of all IPD cases was most common in children under 1 year of age (30%). Particular serotypes were significantly associated with a presentation of meningitis, after controlling for age and year, and the case:carrier ratio varied markedly by serotype. This paper provides a baseline for evaluating the impact of 7-valent pneumococcal conjugate vaccines, introduced in September 2006. Ongoing high-quality laboratory-based surveillance of IPD in all age groups is essential.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.VACCINE.2014.01.035
Abstract: Despite the reduction in adult invasive pneumococcal disease through 'herd protection' consequent to the introduction of childhood pneumococcal conjugate vaccination (PCV), a significant proportion of adults continue to develop pneumococcal pneumonia caused by one of the seven serotypes included in the seven-valent conjugated pneumococcal vaccine (PCV7). The clinical features and outcomes of these adults have not been previously reported. Adults recruited over a three year period to a large prospective cohort study of community acquired pneumonia (CAP) were investigated for pneumococcal serotypes using a validated multiplex immunoassay (Bio-plex). The baseline characteristics and outcomes of adults with PCV7-serotype CAP in comparison to those with non-PCV7-serotype CAP were established. Pneumococcal aetiology was identified in 415 of 1166 (35.6%) in iduals, and a serotype determined in 287 (69.2%). Following exclusion of three in iduals with both a PCV7 and non-PCV7 serotype, 77 of the remaining 284 (27.1%) adults had CAP due to PCV7 serotypes. Adults with PCV7-serotype CAP were older (median years (inter-quartile range) 73.3 (60.8-84.4) versus 65.0 (46.1-78.0) p=0.001) and were more likely to have a World Health Organisation performance status ≥1 (odds ratio (OR) 2.05, 95% confidence interval (CI) 1.21-3.50).The presence of stroke (adjusted OR 2.84, 95% CI 1.36-5.95) and dementia (adjusted OR 3.55, 95% CI 1.26-9.94) as underlying co-morbid illnesses were independently associated with PCV7-serotype CAP 30-day mortality was significantly greater in adults with PCV7-serotype CAP (adjusted OR 4.38, 95% CI 1.85-10.34). A significant proportion of adults continue to develop PCV7-serotype CAP in the era of childhood pneumococcal conjugate vaccination. These adults are more likely to have stroke and dementia as underlying co-morbid illnesses, and have a higher 30-day mortality. A combination of pneumococcal transmission factors, host factors and pneumococcal serotype specific characteristics are likely to explain these findings.
Publisher: European Respiratory Society (ERS)
Date: 18-03-2015
DOI: 10.1183/09031936.00183614
Abstract: Infant 13-valent pneumococcal conjugate vaccination (PCV13) was introduced to the UK in 2010. Its impact on serotypes implicated in adult non-bacteraemic pneumococcal pneumonia is not known. Beginning in 2008, a 5-year prospective cohort study of adults admitted to hospital with community-acquired pneumonia (CAP) was conducted. Pneumococcal serotype was established using a validated multiplex immunoassay (Bio-Plex Bio-Rad, Hercules, CA, USA). The overall incidence for hospitalised CAP and pneumococcal CAP was 79.9 (95% CI 76.6–83.3) and 23.4 (95% CI 21.6–25.3) per 100 000 population, respectively. A decline in CAP (incidence rate ratio (IRR) per year 0.96, 95% CI 0.94–0.99 p=0.016) and pneumococcal CAP (IRR per year 0.84, 95% CI 0.80–0.89 p .001) was observed over the 5-year period of the study. Between the pre- and post-PCV13 periods of the study, the incidence of CAP due to serotypes included in the PCV7 declined by 88% (IRR 0.12, 95% CI 0.08–0.20 p .001), and CAP due to the additional 6 serotypes in PCV13 declined by 30% (IRR 0.70, 95% CI 0.51–0.96 p=0.024). Incidence of adult pneumococcal pneumonia declined over the last 5 years, with serotypes included in PCV13 declining post-PCV13 introduction, indicating early herd protection effects from PCV13 infant vaccination on adult non-bacteraemic disease. These effects may accrue over the coming years with implications for national pneumococcal vaccination policies in adults.
Publisher: BMJ
Date: 18-09-2013
DOI: 10.1136/THORAXJNL-2013-203987
Abstract: On a population level, pneumococcal conjugate vaccination in children has reduced the incidence of vaccine-type disease in all age groups, including older adults. Few in idual level studies have been performed describing the pneumococcal serotypes associated with adult community acquired pneumonia (CAP) and quantifying associations with child contact and child vaccination status. Pneumococcal serotypes were determined using a validated multiplex immunoassay (Bio-Plex) in a large prospective cohort of adults hospitalised with CAP. Child (<16 years old) contact history and child pneumococcal vaccination status were obtained from patients and public health records, respectively. Of 1130 participants, 329 (29.1%) reported child contact, and pneumococcal infection was identified in 410 (36.3%). Pneumococcal CAP was commoner in adults with child contact (148/329 (45.0%) vs 262/801 (32.7%) adjusted OR 1.63, CI 1.25 to 2.14 p<0.001). A serotype was determined in 263 of 410 (64.1%) adults with pneumococcal CAP 112 (42.6%) reported child contact, 38 (33.9%) with a vaccinated child. Adults in contact with a vaccinated child were significantly less likely to have vaccine-type CAP compared with adults in contact with an unvaccinated child (6 of 38 (15.8%) vs 25 of 74 (33.8%), respectively OR 0.37, 95% CI 0.14 to 0.99 p=0.044). Pneumococcal aetiology in adult CAP is independently associated with child contact and implicated serotypes are influenced by child vaccination status. This is the first study to demonstrate these associations at an in idual rather than population level it affirms that 'herd protection' from childhood vaccination extends beyond adult invasive disease to pneumococcal CAP.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JINF.2014.07.002
Abstract: To assess the potential use of a protein-based meningococcal group B (MenB) vaccine (Bexsero(®)) in addition to antibiotic chemoprophylaxis for preventing secondary cases. Published studies on the risk of secondary meningococcal infections were used to estimate the numbers needed to vaccinate (NNV) with Bexsero(®) to prevent a secondary case in household and educational settings. Most secondary cases occur within a few days of diagnosis in the index case. Unlike conjugate vaccines, early protection offered after a single dose of Bexsero(®) is likely to be low, particularly in young children, who are at higher risk of secondary infection. NNV was dependent on predicted meningococcal strain coverage, estimated onset of protection after one Bexsero(®) dose and estimated vaccine efficacy. Even in the most favourable scenario where we assume the vaccine is administered within 4 days of the index case and prevents 90% of cases occurring after 14 days, the NNV for household contacts was >1000. NNV in educational settings was much higher. The estimated NNV should be taken into account when deciding policy to recommend Bexsero(®) for close contacts of single cases in household or educational settings. Bexsero(®) may have a protective role in clusters and outbreaks.
Publisher: Elsevier BV
Date: 10-2015
Publisher: BMJ
Date: 28-02-2012
DOI: 10.1136/THORAXJNL-2011-201092
Abstract: The distribution of pneumococcal serotypes implicated in non-invasive community-acquired pneumonia (CAP) in adults is currently unknown. A prospective observational cohort study was conducted over 2 years in a large U.K. teaching hospital trust. Urine s les, in addition to routine blood and sputum s les, were obtained from consecutive adults admitted to the hospital with CAP. Pneumococcal serotype was determined from urine s les using a validated multiplex immunoassay which detects 14 serotypes. Of 920 patients with CAP, 366 had pneumococcal CAP 242 had a serotype determined. Thirty-day mortality was 10% for all-cause CAP and 9.6% for pneumococcal CAP. Annual incidence of pneumococcal CAP was 36.5 per 100,000, increasing from 12.1 to 274.1 per 100,000 for ages 16-44 years and ≥85 years, respectively. The most prevalent serotypes were 14, 1, 8, 3 and 19A. Less invasive serotypes were significantly associated with increasing age (OR per increasing age group: 1.5, 95% CI 1.2 to 1.9, p<0.001) and co-morbidity (OR per increasing Charlson index group: 1.4, 95% CI 1.0 to 2.0, p=0.036), and with higher 30-day mortality (OR adjusted for age and co-morbidity: 5.5, 95% CI 1.2 to 25.3, p=0.028) compared with highly invasive serotypes. The proportion of patients in whom serotypes contained within the seven-valent childhood pneumococcal conjugate vaccine was identified increased with age (15.6% for patients aged 16-44 years, 41.0% for patients aged ≥85 years p<0.05). In adult invasive and non-invasive pneumococcal CAP, the most common serotypes implicated were 14, 1, 8, 3 and 19A. Age and co-morbidity were associated with the distribution of serotypes identified.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Imogen Molly Cranston.