Are we ready to live without immunisations?

Screen Shot 2016-07-17 at 17.47.46The immune system is like an army, poised and ready to attack: it actually comprises two separate systems, these being the innate and the adaptive immune systems – you could think of these as two separate groups of soldiers i.e. foot soldiers and intelligence officers. The innate immune system responds quickly to threats, it is always on guard but this system is non-specific, meaning that it does not recognise any specific threats and will respond to all threats in the same way – this system could be thought of as the bodies foot soldiers (recognising all types of enemy but always launching the same type of attack). The adaptive immune system is slower since it needs time to recognise the threat but, once this is done, this system can launch a more specific, targeted, attack. This system also has a memory, meaning that after successive encounters with the same threat it will adapt and the next time it encounters the same threat its attack will be faster and more efficient. It is during this type of attack that antibodies are produced. These antibodies stick around in the body and help bolster our immune system and speed up future attacks (it is this process which is augmented through immunisation/vaccination). We could think of this system as the body’s intelligence agency, gathering information on its enemy and launching a targeted attack.

When we receive a vaccine we are attempting to induce an immune response without harming the body. The body is infected by a harmless version of a virus or bacteria that triggers an immune response without making the recipient sick. This then creates an immunological memory so that the next time we are infected by the same pathogen the immune system will be quick to react and the threat will be neutralised before we show any symptoms.

Vaccines have been a major success, they have helped to eliminate most of the childhood diseases that historically caused millions of deaths and are very cost effective. Thanks to this, average life expectancy has increased from 35 years in 1750 to above 80 years today. According to World Health Organization measles vaccination resulted in a 79% drop in measles deaths between 2000 and 2014 worldwide, and according to UNICEF each year immunisation prevents around 2-3 million deaths a year from life-threatening diseases in children.

But some people still choose not immunise their children, stating a range of reasons – from religion to the belief that vaccines are neither effective nor safe. In 1998 the Lancet published a paper by Andrew Wakefield stating that the measles vaccine produced autism in 21 children. Later several peer-reviewed studies failed to show any association between the vaccine and autism and eventually the Lancet’s editors fully retracted Wakefield’s paper claiming deliberate falsification. But, despite a lack of solid evidence and the paper retraction, vaccination rates in the UK dropped to 80% in the years following, leading to an increase in cases of measles across the UK – causing not only deaths but also measles encephalitis. By 2008, measles had become endemic in the UK due to low-vaccinated communities.

Last year there was a case of diphtheria in Spain when a 6-year-old non-immunised boy became infected. Diphtheria is a highly contagious disease caused by a bacterium called Corynebacterium diphtheria. Thanks to immunisation campaigns in Spain the number of cases of diphtheria in the country dropped from 1,000 cases in 100,000 inhabitants in 1945 to 0.10 cases in 100,000 in 1965 – now in 2016 diphtheria is thought to have been eradicated in this area. Therefore when this young boy fell ill last year there were no treatments available in the country at the time. Sadly, despite heroic efforts to import a treatment, the child died. When his parents were asked why he had not been immunised they said they felt tricked and not properly informed by anti-vaccination groups; they thought they were doing the best thing for their child.

So what happens when people decide not to immunise their children? :

Assuming that a large proportion of a population are immunised it is possible that non-immunised individuals may be protected by a process known as herd immunity. Basically, the more people who are immunised, the fewer opportunities a disease has to spread – this confers protection to those who can’t be immunised (such as children with cancer receiving chemotherapy or radiotherapy, children treated with immunosuppressed drugs such as corticosteroids, people with weakened immune system or people allergic to any of the components of the vaccine). This means that these people really depend on those around them being immunised.

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We can lose sight of the benefits of immunisation because we don’t have a memory of living in a world without vaccines. But, diseases that we thought were eradicated a long time ago will come back if we stop immunisation – meaning we could find ourselves confronting epidemics of diseases with the ability to kill hundreds of thousands of children and adults every year. Sadly some diseases will never be fully eradicated because they are found everywhere. For example, tetanus is a serious infection caused by Clostridium tetani bacteria which produces a toxin that affects the brain and nervous system. Clostridium tetani spores can be found most commonly in soil, dust and manure, but also exist virtually anywhere. So a child playing in a sand pit or with just some grass can get in easily infected through a cut or wound on his hands. Therefore, maintaining immunisation is particularly important in the fight against this type of disease.

Although vaccines do come with some side effects, like high temperature or soreness in the injected site, very serious health events post-immunization are rare and the benefits of immunisation clearly exceed the risks of an infection. Thus, the only way to prevent the infection is through immunisation.

Post by: Cristina Ferreras

References:

Rappuoli R et al. Vaccines for the twenty-first century society. Nat Rev Immunol. 2011 Nov 4;11(12):865-72. doi: 10.1038/nri3085. Erratum in: Nat Rev Immunol. 2012 Mar;12(3):225

UNICEF_immunization Facts and Figures April 2013 http://www.unicef.org/immunization/file/UNICEF_Key_facts_and_figures_on_Immunization_April_2013%281%29.pdf

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Ovarian cancer: early diagnosis is the best treatment

The 8th of May was world ovarian cancer day. Ovarian cancer is considered to be the most lethal gynaecological malignancy, being the  fourth most common cause of cancer death in women in the developed world (1). Early stage misdiagnosis is common, especially since symptoms (such as feeling bloating, abdominal pain, difficulty eating or constipation) can be incorrectly attributed to common stomach and digestive complaints. Indeed, of the approximately 7000 new cases diagnosed in the UK each year, only a small percentage of diagnoses (around 20%) (2) will be early stage where the survival rate is over 90%. The key to successful early diagnosis lies in the frequency and the number of symptoms a woman suffers.

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Risk factors and diagnosis:

Common risk factors include: menopause (this being the most significant risk), mutations in genes associated with DNA repair like BRCA1 and BRCA2 genes, family history, infertility or having fertility treatment, endometriosis or being overweight.

There is unfortunately no accurate screening to diagnose ovarian cancer. Current screening practices rely upon CA125 (a tumor marker that can be detected in the blood) screening, alongside abdominal and transvaginal ultrasound (3). However, CA125 screening lacks both specificity and sensitivity. Specifically, CA125 can be detected in a range of cancers and in benign conditions in premenopausal women like endometriosis, pelvic inflammatory disease or even pregnancy, it is also more accurate for late stage diagnosis.

Treatment:

The standard of care for patients with advanced disease involves surgical tumour debulking followed by chemotherapy but sadly most patients will relapse within 18 months and eventually will die from the disease. Over the years clinical trials have been set up to explore combinations of drugs which could improve the prognosis for ovarian cancer patients. One of these therapies is called targeted cancer therapy or biological therapy and involves stopping tumour growth through interfering with tumour biology. Tumours need to spread out to find oxygen and nutrients, a process called angiogenesis (this being crucial for tumour growth and proliferation). Several anti-angiogenic drugs have been developed and are now being tested in preclinical and clinical settings. The aim is to target not the tumour but the surrounding structures (blood vessels) necessary for tumour growth. VEGF is a molecule which is overexpressed in most solid tumours including ovarian cancer and is crucial in tumour angiogenesis. So this molecule represents a good drug target, the rationale being that inhibition of VEGF may eliminate or delay tumour growth. Bevacizumab (Avastin) is a monoclonal antibody that binds VEGF and sequesters it, causing blood vessels growth to stop, thus making it more difficult for the tumour to grow. It is the only anti-angiogenic drug licenced to be used in women with advanced ovarian cancer alongside chemotherapy. However, despite promising results in initial studies it has so far not proved beneficial to overall survival rates and some people consider it not to be cost-effective (4).

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Another targeted cancer therapy used to treat ovarian cancer is inhibition of PARP1 (a molecule involved in DNA repair). This drug is called olaparib and is offered to patients with deficient tumour suppressor proteins BRCA1 and BRCA2 since cells deficient in BRCA1/2 are more sensitive to PARP1 inhibitors. PARP1 and BRCA1/2 are involved in repairing broken DNA, in patients carrying BRCA mutations, inhibition of PARP1 results in cumulative DNA damage and tumor cell death.

There are also a range of antivascular agents (drugs which attacks the blood supply of a tumor) now entering clinical trials (5). We are also making advances in immunologic therapies and in drugs targeting relevant gene mutations but, in some cases, toxic side effects make these treatments unfeasible.

The future:

Despite advances in drug research, early-stage detection is still believed to be the key to improved survival. Therefore continued research into biological markers for early detection and diagnosis is vital. It is hoped that such research, alongside work into finding biomarkers that predict disease progression, drug response and allow us to select patients who benefit the most from a specific treatment option will give us a fighting chance against ovarian cancer.

References

  1. Paik ES, Lee Y-Y, Lee E-J, Choi CH, Kim T-J, Lee J-W, et al. Survival analysis of revised 2013 FIGO staging classification of epithelial ovarian cancer and comparison with previous FIGO staging classification. Obstetrics & Gynecology Science. 2015 ;58(2):124-34.
  2.         Hennesy BT, Coleman RL, Markman M. Ovarian cancer. Lancet 2009. 17;374:1371-82
  3.         Jayson GC, Khon EC, Kitchener HC, Ledermann JA. Ovarian Cancer. Lancet 2014. 2014;384:1376-88.
  4.     Robert H. Carlson. Antiangiogenic Therapy’s Value in Ovarian Cancer Questioned. Oncology Times 12/25/14
  5.        Bell-McGuinn K, Konner J, Tew W, Springgs DR. New drugs for ovarian cancer. Ann Oncol. 2011 Dec;22 Suppl 8:viii77-viii82. doi: 10.1093/annonc/mdr531.

Links of interest:

UK CR. Ovarian Cancer incidence by UK region 2015 [cited 2016 07.01]. Available from: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer/incidence#ref-0.
Post By: Cristina Ferreras

Charity at home and abroad

I am a Spanish scientist. I came to Manchester in 2007 to work as a postdoc in the Paterson Institute for Cancer Research. I have been working in oncology for the last 5 years so here I will focus on this, although what I’m about to speak about could also be extrapolated to many other causes.

image3It has always amazed me how committed people in this country are to fighting cancer. How so many adopt this fight as part of their daily lives; you see charity boxes in so many places (pubs, shops, coffee shops), people run, cycle, climb and swim all to raise money for cancer research. It seems so easy and so rewarding; to the point that it actually seems weird if you don’t get involved in something!

This leads me to question why this does not happen in my country? Is it because we are less supportive, are we so money orientated that we can’t give a penny for these causes or is it that that the Mediterranean diet protect us from cancer so much so that we don’t care or worry as much? Well, not the last one, of all EU countries Spain has the third highest rate of deaths due to cancer in people under 65. But what about the other two? Let’s think about them: are we Spanish people less supportive? I would say no. Spain is the world leader in organ donation and transplantation, which is pretty impressive since we are not a very big country. Not only that but we always show our support in the face of global image1catastrophe, organising call-in TV shows where people give money and which often raise many millions for the cause. So how about the second reason, are we a little bit tight with our money? As I said before, we are not. We as a country are happy to donate whenever we think people need it. We even broadcast TV shows where people can talk about their financial problems and others just call-in and donate money to them,offer them jobs or even give them a local rent free to start up a new business. So why is Cancer Research UK  so much more successful than it’s Spanish counterpart (CRUK raised 661 million pounds in 2014 while it’s Spanish equivalent reached just 44 million)?

There could be several explanations for this. Firstly, when people donate organs their action will have a tangible effect on someone desperate for that organ, it will save a life right away. The same is true for donations made towards global catastrophes, when people donate money to these causes they believe that their money will go to help those whose image2lives have been damaged. But when they donate to cancer research they don’t see any instant benefit, people think it is a waste! Spain is not a leading country in cancer research so why are they going to donate to this cause? However, if people don’t get more involved we are never going to be a leading country. We have no charity shops and barely any money boxes dedicated to this cause. There are very few races organised with very little dissemination in the media. Among my academic friends working in Spain only one was even aware or the existence of World Cancer Day on the 4th of February.

I believe that if more people were to get involved this would encourage many others to do the same. Therefore, making advances in cancer research more likely and showing people a tangible outcome to their charitable donations. It just requires some compromise and support from different institutions and news industry. I hope that in the future this changes because not much has been changed in the last 9 years.

Post by: Cristina Ferreras