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1.  Factors affecting immunogenicity of BCG in infants, a study in Malawi, The Gambia and the UK 
BMC Infectious Diseases  2014;14:184.
Background
BCG immunogenicity in infants differs between populations and these differences have been attributed to various factors. In this study, the influence of geographical location, season of birth, timing of vaccination, micronutrient status (zinc) and inflammatory status (C-reactive protein, CRP) were assessed.
Methods
Immunogenicity was assessed by cytokine signature in culture supernatants from diluted whole blood samples stimulated with M. tuberculosis PPD, using a multiplex bead assay. Results were correlated with the plasma zinc and CRP concentrations at the time of sampling, and with interview and household data. BCG vaccinated infants were recruited in Malawi, The Gambia and the UK.
Results
In Malawi, infants vaccinated within the first week after birth showed lower production of most cytokines measured than those vaccinated later. The number of cytokines showing significant differences between Malawian and Gambian infants decreased after adjusting for season of birth. In Malawi, a proportion of infants had zinc deficiency and elevated plasma CRP (>10 mg/L), but neither zinc deficiency nor high CRP was associated with production of any of the cytokines measured.
Conclusions
The cytokine/chemokine signatures observed in response to M. tuberculosis PPD in infants at 3 months post BCG vaccination were affected by geographical location, season of birth, and timing of vaccination but not associated with the concentration of plasma zinc or inflammatory status. These factors should be considered in future trials of new TB vaccines.
doi:10.1186/1471-2334-14-184
PMCID: PMC4101864  PMID: 24708690
BCG vaccination; CRP; Cytokine; Infant immune response; M. tuberculosis PPD; Zinc
2.  Funding Infectious Disease Research: A Systematic Analysis of UK Research Investments by Funders 1997–2010 
PLoS ONE  2014;9(8):e105722.
Background
Research investments are essential to address the burden of disease, however allocation of limited resources is poorly documented. We systematically reviewed the investments awarded by funding organisations to UK institutions and their global partners for infectious disease research.
Methodology/Principal Findings
Public and philanthropic investments for the period 1997 to 2010 were included. We categorised studies by infectious disease, cross-cutting theme, and by research and development value chain, reflecting the type of science. We identified 6165 funded studies, with a total research investment of UK £2.6 billion. Public organisations provided £1.4 billion (54.0%) of investments compared with £1.1 billion (42.4%) by philanthropic organisations. Global health studies represented an investment of £928 million (35.7%). The Wellcome Trust was the leading investor with £688 million (26.5%), closely followed by the UK Medical Research Council (MRC) with £673 million (25.9%). Funding over time was volatile, ranging from ∼£40 million to ∼£160 million per year for philanthropic organisations and ∼£30 million to ∼£230 million for public funders.
Conclusions/Significance
Infectious disease research funding requires global coordination and strategic long-term vision. Our analysis demonstrates the diversity and inconsistent patterns in investment, with volatility in annual funding amounts and limited investment for product development and clinical trials.
doi:10.1371/journal.pone.0105722
PMCID: PMC4146508  PMID: 25162631
3.  Investing in sepsis research: systematic analysis of UK public and philanthropic funding 1997–2010 
JRSM Open  2014;5(9):2054270414538954.
doi:10.1177/2054270414538954
PMCID: PMC4207276  PMID: 25352990
4.  Influenza vaccination uptake among people aged over 85 years: an audit of primary care practice in the UK 
JRSM Open  2014;5(7):2054270414531122.
doi:10.1177/2054270414531122
PMCID: PMC4100234  PMID: 25057409
5.  Investments in respiratory infectious disease research 1997–2010: a systematic analysis of UK funding 
BMJ Open  2014;4(3):e004600.
Objectives
Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain.
Setting
The UK.
Participants
Institutions that host and carry out infectious disease research.
Primary and secondary outcome measures
The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size.
Results
We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I–IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden.
Conclusions
The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats.
doi:10.1136/bmjopen-2013-004600
PMCID: PMC3975787  PMID: 24670431
respiratory; investments; financing; policy
6.  Systematic analysis of funding awarded for norovirus research to institutions in the United Kingdom, 1997–2010 
Objectives
Norovirus infections pose great economic and disease burden to health systems around the world. This study quantifies the investments in norovirus research awarded to UK institutions over a 14-year time period.
Design
A systematic analysis of public and philanthropic infectious disease research investments awarded to UK institutions between 1997 and 2010.
Participants
None
Setting
UK institutions carrying out infectious disease research.
Main outcome measures
Total funding for infectious disease research, total funding for norovirus research, position of norovirus research along the R&D value chain.
Results
The total dataset consisted of 6165 studies with sum funding of £2.6 billion. Twelve norovirus studies were identified with a total funding of £5.1 million, 0.2% of the total dataset. Of these, eight were categorized as pre-clinical, three as intervention studies and one as implementation research. Median funding was £200,620.
Conclusions
Research funding for norovirus infections in the UK appears to be unacceptably low, given the burden of disease and disability produced by these infections. There is a clear need for new research initiatives along the R&D value chain: from pre-clinical through to implementation research, including trials to assess cost-effectiveness of infection control policies as well as clinical, public health and environmental interventions in hospitals, congregate settings and in the community.
doi:10.1177/0141076813511450
PMCID: PMC3938121  PMID: 24262891
norovirus; research; funding; investments; UK
7.  Systematic analysis of funding awarded for norovirus research to institutions in the United Kingdom, 1997–2010 
Objectives
Norovirus infections pose great economic and disease burden to health systems around the world. This study quantifies the investments in norovirus research awarded to UK institutions over a 14-year time period.
Design
A systematic analysis of public and philanthropic infectious disease research investments awarded to UK institutions between 1997 and 2010.
Participants
None
Setting
UK institutions carrying out infectious disease research.
Main outcome measures
Total funding for infectious disease research, total funding for norovirus research, position of norovirus research along the R&D value chain.
Results
The total dataset consisted of 6165 studies with sum funding of £2.6 billion. Twelve norovirus studies were identified with a total funding of £5.1 million, 0.2% of the total dataset. Of these, eight were categorized as pre-clinical, three as intervention studies and one as implementation research. Median funding was £200,620.
Conclusions
Research funding for norovirus infections in the UK appears to be unacceptably low, given the burden of disease and disability produced by these infections. There is a clear need for new research initiatives along the R&D value chain: from pre-clinical through to implementation research, including trials to assess cost-effectiveness of infection control policies as well as clinical, public health and environmental interventions in hospitals, congregate settings and in the community.
doi:10.1177/0141076813511450
PMCID: PMC3938121  PMID: 24262891
norovirus; research; funding; investments; UK
8.  Systematic analysis of funding awarded for mycology research to institutions in the UK, 1997–2010 
BMJ Open  2014;4(1):e004129.
Objectives
Fungal infections cause significant global morbidity and mortality. We have previously described the UK investments in global infectious disease research, and here our objective is to describe the investments awarded to UK institutions for mycology research and outline potential funding gaps in the UK portfolio.
Design
Systematic analysis.
Setting
UK institutions carrying out infectious disease research.
Primary and secondary outcome measures
Primary outcome is the amount of funding and number of studies related to mycology research. Secondary outcomes are describing the investments made to specific fungal pathogens and diseases, and also the type of science along the R&D value chain.
Methods
We systematically searched databases and websites for information on research studies from public and philanthropic funding institutions awarded between 1997 and 2010, and highlighted the mycology-related projects.
Results
Of 6165 funded studies, we identified 171 studies related to mycology (total investment £48.4 million, 1.9% of all infection research, with mean annual funding £3.5 million). Studies related to global health represented 5.1% of this funding (£2.4 million, compared with 35.6% of all infectious diseases). Leading funders were the Biotechnology and Biological Sciences Research Council (£14.8 million, 30.5%) and Wellcome Trust (£12.0 million, 24.7%). Preclinical studies received £42.2 million (87.3%), with clinical trials, intervention studies and implementation research in total receiving £6.2 million (12.7%). By institution, University of Aberdeen received most funding (£16.9 million, 35%). Studies investigating antifungal resistance received £1.5 million (3.2%).
Conclusions
There is little translation of preclinical research into clinical trials or implementation research in spite of substantial disease burden globally, and there are few UK institutions that carry out significant quantities of mycology research of any type. In the context of global health and the burden of disease in low-income countries, more investment is required for mycology research.
doi:10.1136/bmjopen-2013-004129
PMCID: PMC3902376  PMID: 24413353
MYCOLOGY; BASIC SCIENCES; INFECTIOUS DISEASES
9.  Differences in research funding for women scientists: a systematic comparison of UK investments in global infectious disease research during 1997–2010 
BMJ Open  2013;3(12):e003362.
Objectives
There has not previously been a systematic comparison of awards for research funding in infectious diseases by sex. We investigated funding awards to UK institutions for all infectious disease research from 1997 to 2010, across disease categories and along the research and development continuum.
Design
Systematic comparison.
Methods
Data were obtained from several sources for awards from the period 1997 to 2010 and each study assigned to—disease categories; type of science (preclinical, phases I–III trials, product development, implementation research); categories of funding organisation. Fold differences and statistical analysis were used to compare total investment, study numbers, mean grant and median grant between men and women.
Results
6052 studies were included in the final analysis, comprising 4357 grants (72%) awarded to men and 1695 grants (28%) awarded to women, totalling £2.274 billion. Of this, men received £1.786 billion (78.5%) and women £488 million (21.5%). The median value of award was greater for men (£179 389; IQR £59 146–£371 977) than women (£125 556; IQR £30 982–£261 834). Awards were greater for male principal investigators (PIs) across all infectious disease systems, excepting neurological infections and sexually transmitted infections. The proportion of total funding awarded to women ranged from 14.3% in 1998 to 26.8% in 2009 (mean 21.4%), and was lowest for preclinical research at 18.2% (£285.5 million of £1.573 billion) and highest for operational research at 30.9% (£151.4 million of £489.7 million).
Conclusions
There are consistent differences in funding received by men and women PIs: women have fewer funded studies and receive less funding in absolute and in relative terms; the median funding awarded to women is lower across most infectious disease areas, by funder, and type of science. These differences remain broadly unchanged over the 14-year study period.
doi:10.1136/bmjopen-2013-003362
PMCID: PMC3865386  PMID: 24327360
Infectious Diseases; Public Health; Statistics & Research Methods; Virology; Parasitology; Mycology
10.  Systematic analysis of funding awarded for antimicrobial resistance research to institutions in the UK, 1997–2010 
Objectives
To assess the level of research funding awarded to UK institutions specifically for antimicrobial resistance-related research and how closely the topics funded relate to the clinical and public health burden of resistance.
Methods
Databases and web sites were systematically searched for information on how infectious disease research studies were funded for the period 1997–2010. Studies specifically related to antimicrobial resistance, including bacteriology, virology, mycology and parasitology research, were identified and categorized in terms of funding by pathogen and disease and by a research and development value chain describing the type of science.
Results
The overall dataset included 6165 studies receiving a total investment of £2.6 billion, of which £102 million was directed towards antimicrobial resistance research (5.5% of total studies, 3.9% of total spend). Of 337 resistance-related projects, 175 studies focused on bacteriology (40.2% of total resistance-related spending), 42 focused on antiviral resistance (17.2% of funding) and 51 focused on parasitology (27.4% of funding). Mean annual funding ranged from £1.9 million in 1997 to £22.1 million in 2009.
Conclusions
Despite the fact that the emergence of antimicrobial resistance threatens our future ability to treat many infections, the proportion of the UK infection-research spend targeting this important area is small. There are encouraging signs of increased investment in this area, but it is important that this is sustained and targeted at areas of projected greatest burden. Two areas of particular concern requiring more investment are tuberculosis and multidrug-resistant Gram-negative bacteria.
doi:10.1093/jac/dkt349
PMCID: PMC3886928  PMID: 24038777
antibiotics; antifungal; antiviral; antiparasitic
12.  Determining Mycobacterium tuberculosis Infection among BCG-Immunised Ugandan Children by T-SPOT.TB and Tuberculin Skin Testing 
PLoS ONE  2012;7(10):e47340.
Background
Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population.
Methodology/Principal Findings
We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens.
Conclusions/Significance
We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of children as TB-infected or TB-uninfected difficult. Existing tools for the diagnosis of TB infection are unsatisfactory in determining infection among children in this setting.
doi:10.1371/journal.pone.0047340
PMCID: PMC3471887  PMID: 23077594

Results 1-12 (12)