'A bite before bed': exposure to malaria vectors outside the times of net use in the highlands of western Kenya.

BACKGROUND: The human population in the highlands of Nyanza Province, western Kenya, is subject to sporadic epidemics of Plasmodium falciparum. Indoor residual spraying (IRS) and long-lasting insecticide treated nets (LLINs) are used widely in this area. These interventions are most effective when Anopheles rest and feed indoors and when biting occurs at times when individuals use LLINs. It is therefore important to test the current assumption of vector feeding preferences, and late night feeding times, in order to estimate the extent to which LLINs protect the inhabitants from vector bites. METHODS: Mosquito collections were made for six consecutive nights each month between June 2011 and May 2012. CDC light-traps were set next to occupied LLINs inside and outside randomly selected houses and emptied hourly. The net usage of residents, their hours of house entry and exit and times of sleeping were recorded and the individual hourly exposure to vectors indoors and outdoors was calculated. Using these data, the true protective efficacy of nets (P*), for this population was estimated, and compared between genders, age groups and from month to month. RESULTS: Primary vector species (Anopheles funestus s.l. and Anopheles arabiensis) were more likely to feed indoors but the secondary vector Anopheles coustani demonstrated exophagic behaviour (p < 0.05). A rise in vector biting activity was recorded at 19:30 outdoors and 18:30 indoors. Individuals using LLINs experienced a moderate reduction in their overall exposure to malaria vectors from 1.3 to 0.47 bites per night. The P* for the population over the study period was calculated as 51% and varied significantly with age and season (p < 0.01). CONCLUSIONS: In the present study, LLINs offered the local population partial protection against malaria vector bites. It is likely that P* would be estimated to be greater if the overall suppression of the local vector population due to widespread community net use could be taken into account. However, the overlap of early biting habit of vectors and human activity in this region indicates that additional methods of vector control are required to limit transmission. Regular surveillance of both vector behaviour and domestic human-behaviour patterns would assist the planning of future control interventions in this region.

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.

Simulation of malaria epidemiology and control in the highlands of Western Kenya.

BACKGROUND: Models of Plasmodium falciparum malaria epidemiology that provide realistic quantitative predictions of likely epidemiological outcomes of existing vector control strategies have the potential to assist in planning for the control and elimination of malaria. This work investigates the applicability of mathematical modelling of malaria transmission dynamics in Rachuonyo South, a district with low, unstable transmission in the highlands of western Kenya. METHODS: Individual-based stochastic simulation models of malaria in humans and a deterministic model of malaria in mosquitoes as part of the OpenMalaria platform were parameterized to create a scenario for the study area based on data from ongoing field studies and available literature. The scenario was simulated for a period of two years with a population of 10,000 individuals and validated against malaria survey data from Rachuonyo South. Simulations were repeated with multiple random seeds and an ensemble of 14 model variants to address stochasticity and model uncertainty. A one-dimensional sensitivity analysis was conducted to address parameter uncertainty. RESULTS: The scenario was able to reproduce the seasonal pattern of the entomological inoculation rate (EIR) and patent infections observed in an all-age cohort of individuals sampled monthly for one year. Using an EIR estimated from serology to parameterize the scenario resulted in a closer fit to parasite prevalence than an EIR estimated using entomological methods. The scenario parameterization was most sensitive to changes in the timing and effectiveness of indoor residual spraying (IRS) and the method used to detect P. falciparum in humans. It was less sensitive than expected to changes in vector biting behaviour and climatic patterns. CONCLUSIONS: The OpenMalaria model of P. falciparum transmission can be used to simulate the impact of different combinations of current and potential control interventions to help plan malaria control in this low transmission setting. In this setting and for these scenarios, results were highly sensitive to transmission, vector exophagy, exophily and susceptibility to IRS, and the detection method used for surveillance. The level of accuracy of the results will thus depend upon the precision of estimates for each. New methods for analysing and evaluating uncertainty in simulation results will enhance the usefulness of simulations for malaria control decision-making. Improved measurement tools and increased primary data collection will enhance model parameterization and epidemiological monitoring. Further research is needed on the relationship between malaria indices to identify the best way to quantify transmission in low transmission settings. Measuring EIR through mosquito collection may not be the optimal way to estimate transmission intensity in areas with low, unstable transmission.

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.

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.

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.

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 Spearman's 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.

Genetically engineered parasites: the solution to designing an effective malaria vaccine?

Genetic engineering provides an ingenious method of attenuating Plasmodium falciparum parasites for next generation vaccines. A novel approach stimulates new optimism in the struggle to eliminate the burden of malaria.