BackgroundInfectious diseases account for a significant global burden of disease and substantial investment in research and development. This paper presents a systematic assessment of research investments awarded to UK institutions and global health metrics assessing disease burden.MethodsWe systematically sourced research funding data awarded from public and philanthropic organisations between 1997 and 2013. We screened awards for relevance to infection and categorised data by type of science, disease area and specific pathogen. Investments were compared with mortality, disability-adjusted life years (DALYs) and years lived with disability (YLD) across three time points.FindingsBetween 1997–2013, there were 7398 awards with a total investment of £3.7 billion. An increase in research funding across 2011–2013 was observed for most disease areas, with notable exceptions being sexually transmitted infections and sepsis research where funding decreased. Most funding remains for pre-clinical research (£2.2 billion, 59.4%). Relative to global mortality, DALYs and YLDs, acute hepatitis C, leishmaniasis and African trypanosomiasis received comparatively high levels of funding. Pneumonia, shigellosis, pertussis, cholera and syphilis were poorly funded across all health metrics. Tuberculosis (TB) consistently attracts relatively less funding than HIV and malaria.InterpretationMost infections have received increases in research investment, alongside decreases in global burden of disease in 2013. The UK demonstrates research strengths in some neglected tropical diseases such as African trypanosomiasis and leishmaniasis, but syphilis, cholera, shigellosis and pneumonia remain poorly funded relative to their global burden. Acute hepatitis C appears well funded but the figures do not adequately take into account projected future chronic burdens for this condition. These findings can help to inform global policymakers on resource allocation for research investment.

BackgroundUniversities are significant contributors to research and technologies in health; however, the health needs of the world’s poor are historically neglected in research. Medical discoveries are frequently licensed exclusively to one producer, allowing a monopoly and inequitable pricing. Similarly, research is often published in ways that make it inaccessible. Universities can adopt policies and practices to overcome neglect and ensure equitable access to research and its products.MethodsFor 25 United Kingdom universities, data on health research funding were extracted from the top five United Kingdom funders’ databases and coded as research on neglected diseases (NDs) and/or health in low- and lower-middle-income countries (hLLMIC). Data on intellectual property licensing policies and practices and open-access policies were obtained from publicly available sources and by direct contact with universities. Proportions of research articles published as open-access were extracted from PubMed and PubMed Central.ResultsAcross United Kingdom universities, the median proportion of 2011–2014 health research funds attributable to ND research was 2.6% and for hLLMIC it was 1.7%. Overall, 79% of all ND funding and 74% of hLLMIC funding were granted to the top four institutions within each category. Seven institutions had policies to ensure that technologies developed from their research are affordable globally. Mostly, universities licensed their inventions to third parties in a way that confers monopoly rights. Fifteen institutions had an institutional open-access publishing policy; three had an institutional open-access publishing fund. The proportion of health-related articles with full-text versions freely available online ranged from 58% to 100% across universities (2012–2013); 23% of articles also had a creative commons CC-BY license.ConclusionThere is wide variation in the amount of global health research undertaken by United Kingdom universities, with a large proportion of total research funding awarded to a few institutions. To meet a level of research commitment in line with the global burden of disease, most universities should seek to expand their research activity. Most universities do not license their intellectual property in a way that is likely to encourage access in resource-poor settings, and lack policies to do so. The majority of recent research publications are published open-access, but not as gold standard (CC-BY) open-access.Electronic supplementary materialThe online version of this article (doi:10.1186/s12961-016-0148-6) contains supplementary material, which is available to authorized users.

BackgroundProne positioning has a beneficial role in COVID-19 patients receiving ventilation but lacks evidence in awake non-ventilated patients, with most studies being retrospective, lacking control populations and information on subjective tolerability.MethodsWe conducted a prospective, single-centre study of prone positioning in awake non-ventilated patients with COVID-19 and non-COVID-19 pneumonia. The primary outcome was change in peripheral oxygenation in prone versus supine position. Secondary outcomes assessed effects on end-tidal CO2, respiratory rate, heart rate, and subjective symptoms. We also recruited healthy volunteers to undergo proning during hypoxic challenge.Results238 hospitalised patients with pneumonia were screened; 55 were eligible with 25 COVID-19 patients and 3 non-COVID-19 patients agreeing to undergo proning – the latter insufficient for further analysis. 10 healthy control volunteers underwent hypoxic challenge. Patients with COVID-19 had a median age of 64 years (interquartile range [IQR] 53–75). Proning led to an increase in SpO2 compared to supine position (difference +1.62%; p=0.003) and occurred within 10 min of proning. There were no effects on end-tidal CO2, respiratory rate, or heart rate. There was an increase in subjective discomfort (p=0.003), with no difference in breathlessness. Among healthy controls undergoing hypoxic challenge, proning did not lead to a change in SpO2 or subjective symptom scores.ConclusionIdentification of suitable patients with COVID-19 requiring oxygen supplementation from general ward environments for awake proning is challenging. Prone positioning leads to a small increase in SpO2 within 10 min of proning though is associated with increased discomfort.

Highly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full-length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole-blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We, therefore, propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full-length SIC permits the development of protective antibodies against all SIC domains.

Highly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We therefore propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full length SIC permits development of protective antibodies against all SIC domains.