Tag Archives: Peter Chilton

Vaccinating Against Mosquitoes

Getting bit by a mosquito could potentially lead to a wide variety of infections – dengue, yellow fever, Zika, malaria, etc. The usual method to try to prevent the spread of these diseases is vaccination, but this is hindered in most of these diseases due to the various sub-types and strain variations. But what if there was another way? That is what Jessica Manning and colleagues are looking into – developing a vaccine against mosquito saliva.[1] When a mosquito bites a person, it first injects its saliva into the blood stream before drinking blood, which triggers the person’s innate immune response. This immune response can then inadvertently help spread any pathogens through the lymphatic system. However, the authors hypothesise that by vaccinating a person against the saliva itself then the body will have a different, targeted immune response, which can hopefully destroy the pathogens before they spread and cause infection. A proof of principle has already been shown in animals that have been vaccinated against sand fly saliva, which prevents infection by Leishmania.

Although there is still a long way to go, it is an interesting approach that should be closely monitored.

— Peter Chilton, Research Fellow

Reference:

  1. Manning JE, Morens DM, Kamhawi S, Valenzuela JG, Memoli M. Mosquito Saliva: The Hope for a Universal Arbovirus Vaccine? J Infect Dis. 2018; 218 (1): 7-15.
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Are You Getting Enough?

Most people are aware of the importance of getting a good night’s sleep, but for many actually achieving this amidst work, household chores, children and needing to binge the latest television series, it is difficult. How dangerous is a lack of sleep though? A recent study [1] looked at data from over 43,000 Swedish people, followed up over 13 years, and found that adults (under the age of 65) who slept for fewer than five hours a night all week have a higher mortality risk compared to those who sleep for six or seven hours (hazard ratio 1.65, 95% confidence intervals 1.22-2.23). However, this could be counteracted by getting longer sleep on the weekend – people who had no more than five hours in the week, but were able to get at least eight hours on the weekend had no increased mortality. On the other end of the scale, the research also found that those people who regularly slept for more than eight hours also had a higher rate of mortality compared to those with six or seven hours (hazard ratio 1.25, 95% CI 1-05-1.50). After the age of 65 there doesn’t appear to be any differences. Of course, it is unknown what the causal relationship is between sleep and mortality, and the authors suggest that underlying health problems could be the cause of both extreme sleep patterns and increased mortality.

— Peter Chilton, Research Fellow

References:

  1. Åkerstedt T, Ghilotti F, Grotta A, Zhao H, Adami HO, Trolle-Lagerros Y, Bellocco R. Sleep duration and mortality – does weekend sleep matter? J Sleep Res. 2018.

Widespread Use of Antibiotics to Reduce Child Mortality

As discussed in our previous News Blog,[1] the rise in antibiotic resistance is a worrying situation, and it is widely recommended to limit the prescription of antibiotics to patients who are confirmed to have a treatable bacterial infection. However, a recent trial in three sub-Saharan African countries did the exact opposite with a mass distribution of azithromycin, a broad-spectrum antibiotic, to children under five with the aim of reducing child mortality.[2] This was a cluster-randomised trial of around 190,000 children in 1,533 communities of Malawi, Niger and Tanzania who were assigned to receive four biannual doses of antibiotic or a placebo. Overall, the mortality rate was 14.6 deaths per 1,000 person-years in areas that received the antibiotic, compared to 16.5 deaths in communities that received the placebo, while mortality was also 13.5% lower (95% confidence interval, 6.7-19.8) (p<0.001). The effect was greatest in the youngest sub-group of children, those aged between one and five months, with the authors estimating that one in four expected deaths were prevented due to administration of the antibiotic. There were no differences in serious adverse events within a week of administration. If this strategy was to be more widely rolled out, one approach to combat resistance developing would be to limit it to the populations most in need and only for a short time.[3]

— Peter Chilton, Research Fellow

References:

  1. Chilton PJ. Non-Antibiotic Medicines May Increase Antibiotic Resistance. NIHR CLAHRC West Midlands News Blog. 18 May 2018.
  2. Keenan JD, Bailey RL, West SK, Arzika AM, for the MORDOR Study Group. Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. New Engl J Med. 2018; 378: 1583-92.
  3. Maxmen A. Giving at-risk children pre-emptive antibiotics reduces deaths. Nature. 25 April 2018.

Non-Antibiotic Medicines May Increase Antibiotic Resistance

Alexander Fleming predicted the emergence of antibiotic resistance, and he was soon proved right. The increase in antibiotic resistant bacteria has been at least partially due to the over prescribing of antibiotics by GPs, healthcare centres, etc.[1] Steps have been taken in­­ recent years to combat this,[2] though a recent database study by Smieszek, et al. estimated that between 8.8%-23.1% of antibiotic prescriptions in English primary care were inappropriate,[3] and the situation is much worse in low- and middle-income countries.[4] Now, a study published in Nature by staff from the European Molecular Biology Laboratory has found potential risk from prescribing non-antibiotics.[5]

Previous research has found that medication that targets human cells, as opposed to microbes (for example, anti-diabetics, proton pump inhibitors, non-steroidal anti-inflammatory drugs) may alter the composition of the gut flora. In order to determine the extent of such effects the authors tested over 1,000 drugs against 40 human gut bacterial strains. They found that 24% of those with human targets inhibited the growth of at least one of the strains (and 5% affected at least ten strains). While this could offer new avenues for future drug-therapy research and personalised medicine, the authors also found strong correlation between resistance to antibiotics and to drugs that target human cells, likely due to common mechanisms conferring resistance. This means there is a potential risk of non-antibiotics promoting antibiotic resistance in some bacteria – a concern with the large amount of non-antibiotics taken on a regular basis by a large number of people.

— Peter Chilton, Research Fellow

References:

  1. Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, Laxminarayan R. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014; 14(8): 742-50.
  2. Hoffman SJ, Outterson K, Røttingen J-A, et al. An international legal framework to address antimicrobial resistance. Bull World Health Organ. 2015; 93(2): 66.
  3. Smieszek T, Pouwels KB, Dolk FCK, et al. Potential for reducing inappropriate antibiotic prescribing in English primary care. J Antimicrobial Chemo. 2018; 73(s2): ii36-43.
  4. Das J, Chowdhury A, Hussam R, Banerjee AV. The impact of training informal health care providers in India: A randomized controlled trial. Science. 2016; 354: aaf7384.
  5. Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018; 555: 623-8.

Prescribing Homeopathic Medicine

While there is no experimental evidence that homeopathy works,[1] and NHS England recommend that it no longer be prescribed,[2] it continues to be prescribed by a number of healthcare professionals and is still licensed by the MHRA.[3] Many have argued that even if it doesn’t work there is no harm in using it as long as conventional medicine and/or treatments are also used, and that might even benefit some patients through the placebo effect. However, a recent paper lead by Ben Goldacre reveals a different story.[4]

The authors looked at all 7,618 primary care practices in England over a six month period and found that 8.5% prescribed homeopathy. Those practices that were in the lowest scoring quartile for general prescribing quality (as assessed through cost-effectiveness, efficacy and safety of prescribed medicines) were 2.1 times (95% confidence interval: 1.6-2.8) more likely to prescribe homeopathy when compared to those practices in the highest quartile. Further, practices that spent the most on medicines that were of ‘low value’ were 2.6 times as likely (95% CI 1.9-3.6) to prescribe homeopathy. There was no significant association between homeopathy prescription and patient outcomes or patient recommendation.

Although these associations are unlikely to be directly causal, the authors argue that it is likely to reflect underlying features of the practice, such as respect for best practice guidelines. The CLAHRC WM Director is an unreformed upholder of The Enlightenment and holds no truck with homeopathy.

 — Peter Chilton, Research Fellow

References:

  1. National Health and Medical Research Council. NHMRC Statement on Homeopathy and NHMRC Information Paper – Evidence on the effectiveness of homeopathy for treating health conditions. 2015.
  2. NHS England. Items which should not routinely be prescribed in primary care: Guidance for CCGs. 2017.
  3. Medicines and Healthcare products Regulatory Agency. Register a homeopathic medicine or remedy. 19 October 2017.
  4. Walker AJ, Croker R, Bacon S, et al. Is use of homeopathy associated with poor prescribing in English primary care? A cross-sectional study. J Roy Soc Med. 2018.

Vaccine in Pill Form

Storage of vaccines is an issue faced in a number of low- and middle-income countries due to the need for constant refrigeration. Some sites may have intermittent power or outages, they may simply not have the storage space for the necessary number of vaccines, or there may be difficulty in maintaining a cold temperature during transportation. A recent proof-of-concept study by Miles, et al.[1] may offer hope in the future though. The team based at Cardiff University produced a prototype oral polypeptide vaccine that was able to provide protection against the ‘flu in a mouse model. Previous polypeptide vaccines had poor stability, which hindered transport and thus therapeutic potential. For this vaccine the researchers created highly stable antigenic ‘mimics’ that did not exist in nature. It was stable in both human serum and gastric acid, was able to stimulate and prime an immune response specific to human ‘flu that was as effective as the standard biological equivalent, and remained immunogenic after being administered orally. Although there is still quite a way to go, it is worth keeping an eye on development of these encouraging findings.

— Peter Chilton, Research Fellow

Reference:

  1. Miles JM, Tan MP, Dolton G, et al. Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry. J Clin Invest. 2018.

What Do You Think When You Hear ‘Scientist’?

If you have spent much time in universities you may have seen various stickers or leaflets raising awareness of campaigns that support women in STEM fields (science, technology, engineering and mathematics). There has been a push in recent years to get more girls and women into STEM subjects. Fifty-two percent of those who graduated in STEM disciplines in 2014 were female.[1] This varies widely between disciplines though, with females making up around 80% of graduates in subjects allied to medicine or veterinary sciences, but only around 15% in computer science or engineering and technology. While the gender balance of all STEM graduates are roughly equal, this is not reflected in employment however, with figures suggesting around 23% of employees in UK STEM industries are female,[1] while data from the UNESCO Institute for Statistics less than 30% of scientific researchers worldwide are female.[2]

Does the future hold more promise? A meta-analysis by Miller and colleagues looked at fifty years worth of studies where school children were asked to draw a scientist and examined the genders depicted.[3] They found that over time the percentage showing female scientists has increased – from 0.6% in data collected in 1966-77 to around 40% in 2015. However, when looking at the age of children (in studies since the 1980s) they found that while there was roughly equal representation of male and female scientists among 5 and 6 year olds, by the age of 7-8 years significantly more men were drawn. In the drawings made by girls only, the switch from predominantly female to male depictions happened around 10-11 years. Perhaps with an increase in female representation in STEM roles, especially in public, then young girls might be more likely to see themselves in such a field and thus increase the proportion in the workplace. Equally more needs to be done to emphasise gender equality at these key developmental milestones.

— Peter Chilton, Research Fellow

References:

  1. WISE Campaign for Gender Balance in Science, Technology & Engineering. Women in STEM workforce 2017. 24 October 2017.
  2. UNESCO Institute for Statistics. Women in Science. Fact Sheet No. 43. March 2017.
  3. Miller DI, Nolla KM, Eagly AH, Uttal DH. The Development of Children’s Gender-Science Stereotypes: A Meta-analysis of 5 Decades of U.S. Draw-A-Scientist Studies. Child Development. 2018.

On the Origins of Sickle Cell Anaemia

Nearly every biology and medicine student will have learnt about the link between sickle cell anaemia (SCA) and protection from malaria. If a person inherits two faulty alleles of the haemoglobin gene then their red blood cells will be sickle shaped, which can result in pain, anaemia, swelling, infections and stroke. If they inherit only one faulty allele then the other, non-mutated allele, will ensure they are unlikely to have any symptoms of SCA – they will only be a carrier. If a SCA carrier is infected with the malaria parasite it is unable to reproduce in their red blood cells and so the person is less likely to develop malaria, or will suffer less severe symptoms.

Authors of a recent paper [1] in the American Journal of Human Genetics have traced the origin of the sickle allele through the use of whole-genome-sequence data from around 3,000 people. There are five main haplotypes of the sickle allele that cause varying severity of SCA, but it is unknown if these were caused by relatively recent independent occurrences of the same mutation, or a single mutation a longer time ago, from which they all originated. It turned out that there was a single mutation, which occurred 259 generations ago, or roughly 7,300 years ago, most likely in either the Sahara or west-central Africa. From this it spread to other areas in Africa, probably due to the protection it afforded against malaria, and then beyond. It is hoped that this finding will allow better medical care to be provided, and to predict the severity of a patient’s SCA.

— Peter Chilton, Research Fellow

Reference:

  1. Shriner D & Rotimi CN. Whole-Genome-Sequence-Based Haplotypes Reveal Single Origin of the Sickle Allele during the Holocene Wet Phase. AJHG. 2018.

Conflicts of Interest in Textbooks

An important thing to consider when reading research, especially something that shows new and promising results, is to check the conflicts of interests of the authors. For example, we will naturally be more sceptical about a study on breastfeeding if it is authored by researchers with connections to the formula industry, or a study showcasing the effectiveness of a new drug authored by researchers working for the pharmaceutical company. That is not to say that the studies are inherently biased, but that they should be viewed in a different light to studies that do not have such conflicts. As such, it is alarming to read a recent study by Piper, et al. that found that a considerable proportion of the authors of healthcare textbooks had undisclosed conflicts of interest,[1] stemming from patents on medical devices and remuneration from medical product companies. The textbooks chosen were all used in educating and training of physicians, pharmacists and dentists, and as references for treatments, etc. Perhaps textbook publishers need to follow the lead of academic journals and clearly state any conflicts. Until then, make sure to carefully consider what you read in textbooks.

— Peter Chilton, Research Fellow

Reference:

  1. Piper BJ, Lambert DA, Keefe RC, Smukler PU, Selemon NA, Duperry ZR. Undisclosed Conflicts of Interests among Biomedical Textbook Authors. AJOB Empir Bioeth. 2018. [ePub].

Hazards of Working in an Office

They are becoming increasingly prevalent in our office environment – in fact you might be reading this news blog only a few feet away from one. In an attempt to curb the sedentary lifestyle of many office workers a number of us are turning to the standing desk. A number of studies have shown the dangers of excessive sitting, with it being linked to obesity, type 2 diabetes, various cancers and an increase in mortality. A 2016 meta-analysis of data from over 1 million people suggested that 60-75 minutes of exercise each day could eliminate the increase in mortality,[1] and many companies now recommend workers take regular breaks from their desk and go for a short walk. To this end many now advocate the use of standing desks. However, a recent pilot study found that participants who used a standing desk for a period of two hours had increased levels of discomfort, lowered sustained attention reaction time, and deterioration in their mental state.[2] On the other hand, there was an improvement in creative problem-solving.

Although this was only a short pilot study, it may be worth further investigation. It is plausible that spending an entire working day standing is as unhealthy as spending it sitting – the best option could be alternating positions throughout the day.

— Peter Chilton, Research Fellow

References:

  1. Ekelund W, Steene-Johannessen J, Brown WJ, Fagerland MW, Owen N, Powell KE, et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. Lancet. 2016; 388: 1302-10.
  2. Baker R, Coenen P, Howie E, Lee J, Williamson A, Straker L. A detailed description of the short-term musculoskeletal and cognitive effects of prolonged standing for office computer work. Ergonomics. 2018. [ePub]