Fatima B Wurie

UK investments in global infectious disease research 1997–2010: a case study

BACKGROUND Infectious diseases account for 15 million deaths per year worldwide, and disproportionately affect young people, elderly people, and the poorest sections of society. We aimed to describe the investments awarded to UK institutions for infectious disease research. METHODS We systematically searched databases and websites for information on research studies from funding institutions and created a comprehensive database of infectious disease research projects for the period 1997-2010. We categorised studies and funding by disease, cross-cutting theme, and by a research and development value chain describing the type of science. Regression analyses were reported with Spearmans rank correlation coefficient to establish the relation between research investment, mortality, and disease burden as measured by disability-adjusted life years (DALYs). FINDINGS We identified 6170 funded studies, with a total research investment of UK£2·6 billion. Studies with a clear global health component represented 35·6% of all funding (£927 million). By disease, HIV received £461 million (17·7%), malaria £346 million (13·3%), tuberculosis £149 million (5·7%), influenza £80 million (3·1%), and hepatitis C £60 million (2·3%). We compared funding with disease burden (DALYs and mortality) to show low levels of investment relative to burden for gastrointestinal infections (£254 million, 9·7%), some neglected tropical diseases (£184 million, 7·1%), and antimicrobial resistance (£96 million, 3·7%). Virology was the highest funded category (£1 billion, 38·4%). Leading funding sources were the Wellcome Trust (£688 million, 26·4%) and the Medical Research Council (£673 million, 25·8%). INTERPRETATION Research funding has to be aligned with prevailing and projected global infectious disease burden. Funding agencies and industry need to openly document their research investments to redress any inequities in resource allocation. FUNDING None.

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.

Differences in research funding for women scientists: a systematic comparison of UK investments in global infectious disease research during 1997–2010

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.

Investments in respiratory infectious disease research 1997-2010: a systematic analysis of UK funding.

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.

Bioaerosol production by patients with tuberculosis during normal tidal breathing: implications for transmission risk

Background The size and concentration of exhaled bioaerosols may influence TB transmission risk. This study piloted bioaerosol measurement in patients with TB and assessed variability in bioaerosol production during normal tidal breathing. Understanding this may provide a tool for assessing heterogeneity in infectivity and may inform mathematical models of TB control practices and policies. Methods Optical particle counter technology was used to measure aerosol size and concentration in exhaled air (range 0.3–20 µm in diameter) during 15 tidal breaths across four groups over time: healthy/uninfected, healthy/Mycobacterium tuberculosis-infected, patients with extrathoracic TB and patients with intrathoracic TB. High-particle production was defined as any 1–5 µm sized bioaerosol count above the median count among all participants (median count=2 counts/L). Results Data from 188 participants were obtained pretreatment (baseline). Bioaerosol production varied considerably between individuals. Multivariable analysis showed intrathoracic TB was associated with a 3½-fold increase in odds of high production of 1–5 µm bioaerosols (adjusted OR: 3.5; 95% CI 1.6 to 7.8; p=0.002) compared with healthy/uninfected individuals. Conclusions We provide the first evidence that intrathoracic TB increases bioaerosol production in a particle size range that could plausibly transport M. tuberculosis. There is substantial variation in production within patients with TB that may conceivably relate to the degree of infectivity. Further data is needed to determine if high bioaerosol production during tidal breathing is associated with infectiousness.

Comparing research investment to United Kingdom institutions and published outputs for tuberculosis, HIV and malaria: A systematic analysis across 1997-2013

BackgroundThe “Unfinished Agenda” of infectious diseases is of great importance to policymakers and research funding agencies that require ongoing research evidence on their effective management. Journal publications help effectively share and disseminate research results to inform policy and practice. We assess research investments to United Kingdom institutions in HIV, tuberculosis and malaria, and analyse these by numbers of publications and citations and by disease and type of science.MethodsInformation on infection-related research investments awarded to United Kingdom institutions across 1997–2010 were sourced from funding agencies and individually categorised by disease and type of science. Publications were sourced from the Scopus database via keyword searches and filtered to include only publications relating to human disease and containing a United Kingdom-based first and/or last author. Data were matched by disease and type of science categories. Investment (United Kingdom pounds) and publications were compared to generate an ‘investment per publication’ metric; similarly, an ‘investment per citation’ metric was also developed as a measure of the usefulness of research.ResultsTotal research investment for all three diseases was £1.4 billion, and was greatest for HIV (£651.4 million), followed by malaria (£518.7 million) and tuberculosis (£239.1 million). There were 17,271 included publications, with 9,322 for HIV, 4,451 for malaria, and 3,498 for tuberculosis. HIV publications received the most citations (254,949), followed by malaria (148,559) and tuberculosis (100,244). According to UK pound per publication, tuberculosis (£50,691) appeared the most productive for investment, compared to HIV (£61,971) and malaria (£94,483). By type of science, public health research was most productive for HIV (£27,296) and tuberculosis (£22,273), while phase I–III trials were most productive for malaria (£60,491). According to UK pound per citation, tuberculosis (£1,797) was the most productive area for investment, compared to HIV (£2,265) and malaria (£2,834). Public health research was the most productive type of science for HIV (£2,265) and tuberculosis (£1,797), whereas phase I–III trials were most productive for malaria (£1,713).ConclusionsWhen comparing total publications and citations with research investment to United Kingdom institutions, tuberculosis research appears to perform best in terms of efficiency. There were more public health-related publications and citations for HIV and tuberculosis than other types of science. These findings demonstrate the diversity of research funding and outputs, and provide new evidence to inform research investment strategies for policymakers, funders, academic institutions, and healthcare organizations.

Funding Infectious Disease Research: A Systematic Analysis of UK Research Investments by Funders 1997–2010

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.

Cohort Profile: The Flu Watch Study

Influenza is a common, highly contagious respiratory virus which infects all age groups, causing a range of outcomes from asymptomatic infection and mild respiratory disease to severe respiratory disease and death.1 If infected, the adaptive immune system produces a humoral (antibody) and cell-mediated (T cell) immune response to fight the infection.2 Influenza viruses continually evolve through antigenic drift, resulting in slightly different ‘seasonal’ influenza strains circulating each year. Population-level antibody immunity to these seasonal viruses builds up over time, so in any given season only a proportion of the population is susceptible to the circulating strains. Occasionally, influenza A viruses evolve rapidly through antigenic shift by swapping genes with influenza viruses usually circulating in animals. This process creates an immunologically distinct virus to which the population may have little to no antibody immunity. The virus can result in a pandemic if a large portion of the population is susceptible and the virus is easily spread.

Characteristics of exhaled particle production in healthy volunteers: possible implications for infectious disease transmission.

The size and concentration of exhaled particles may influence respiratory infection transmission risk. We assessed variation in exhaled particle production between individuals, factors associated with high production and stability over time. We measured exhaled particle production during tidal breathing in a sample of 79 healthy volunteers, using optical particle counter technology. Repeat measurements (several months after baseline) were obtained for 37 of the 79 participants. Multilevel linear regression models of log transformed particle production measures were used to assess risk factors for high production. Stability between measurements over time was assessed using Lin’s correlation coefficients. Ninety-nine percent of expired particles were <1μm in diameter. Considerable variation in exhaled particle production was observed between individuals and within individuals over time. Distribution of particle production was right skewed. Approximately 90% of individuals produce <150 particles per litre in normal breathing. A few individuals had measurements of over 1000 particles per litre (maximum 1456). Particle production increased with age (p<0.001) and was associated with high tree pollen counts. Particle production levels did not remain stable over time [rho 0.14 (95%CI -0.10, 0.38, p=0.238)]. Sub-micron particles conducive to airborne rather than droplet transmission form the great majority of exhaled particles in tidal breathing. There is a high level of variability between subjects but measurements are not stable over time. Production increases with age and may be influenced by airway inflammation caused by environmental irritants. Further research is needed to determine whether the observed variations in exhaled particle production affect transmission of respiratory infection.

Estimating the Hospital Burden of Norovirus-Associated Gastroenteritis in England and Its Opportunity Costs for Nonadmitted Patients

Since the introduction of rotavirus vaccination in England in July 2013, norovirus has become the second-largest contributor of inpatient gastroenteritis, preventing 57800 patients from being admitted annually. Economic costs amount to £297.7 million, which translates into 6300 quality-adjusted life years.