A spoonful of healthy poo drives a persistent superbug away

Faecal transplantation has been shown to be effective against the superbug Clostridium difficile (C. difficile). This post explores the results from the recent study.

Good gut bacteria in the form of probiotics, are used to foster intestinal microbial balance by   combating nasty bacteria. These are now regularly used in the form of yoghurt or pills.  New studies show a messier and unorthodox approach for combating the deadly ones - a dose of poo from healthy donors. A recent study from Netherlands shows that this approach could keep a superbug Clostridium difficile (C. difficile) at bay.

Commonly affecting older people patients staying in hospital, C. difficile infection is a bacterial infection that affects the digestive system. Though on the decline in the UK, thanks to increased thrust placed on sanitation in hospitals, in 2011 there were 2,053 deaths in England and Wales involving this infection. Scientists now have resounding data that show that the armoury for this deadly hospital superbug resides in faeces of healthy donors.  

C. diificile is notorious to treat. Current treatment involves antibiotics (Vancomycin) often does not provide a lasting response, resulting in repeated treatment and poor response in patients. As early as 2000, in a small study, scientists treated patients with donor faeces using a nasogastric tube and showed that it was effective. In the recent study at the Academic Medical Centre in Amsterdam, scientists conducted a randomized controlled trial, in patients who had a relapse of C. difficile infection following at least one course of adequate antibiotic therapy. Three treatment regimens were compared.

1. Infusion of donor feces preceded by a shortened treatment of vancomycin and bowel lavage (irrigation of stomach)- Infusion group

2. Routine protocol of vancomycin treatment- Vancomycin alone group

3. Routine  vancomycin regimen with bowel lavage- Vancomycin with lavage group

To identify healthy donors, questionnaires pertaining to health were used. Then the faeces from donors were screened for several parasites and blood screened for HIV; human T-cell lymphotropic virus types 1 and 2; hepatitis A, B, and C; cytomegalovirus; Epstein–Barr virus. Faeces from the 'safe' donors were diluted, the solution the  infused into patients through a nasoduodenal tube.

81% of the patients in the infusion group were cured after the first infusion of donor faeces. The remaining patients, received a second infusion with faeces from a different donor at various time points. In total, donor faeces  cured 94% of the patients. 31% of patients in the vancomycin-alone group were cured so were 23% in the group receiving vancomycin with bowel lavage. Cumulatively, the studies showed that  in patients with recurrent C. difficile infection, the infusion of donor faeces resulted in better outcomes when compared to the standard antibiotic treatment. Importantly, patients with multiple relapses of C. difficile infection benefited from this unusual approach.

When the faecal microbiota from some patients, prior to the transfer of the donor faecal solution was analysed, the diversity was consistently low. However within 2 weeks of the infusion, the diversity increased, and was not distinguishable from that of the donors, meaning that the donor microbiota had colonised and thrived in the recipient. Upon follow up studies, the diversity of faecal microbiota remained indistinguishable from that of the donor.

Transplantation of stool from donors, though not common, has been used successfully since late 1950’s. This approach has been proposed for the alleviating several diseases including colitis and irritable bowel syndrome. Whilst the results from this study are exceedingly encouraging, there are several unanswered questions, some hinging on long- term safety of the procedure and others on the awkward nature of infusions. It also remains to be seen whether this unconventional procedure would be acceptable, though this might not be a hurdle, when it is a matter of life and death. Perhaps this is one of the early rungs of innovation in the field, and in the future we may see better ways to introduce the stool bugs.
  

Nieuwdorp M, van Nood E, Speelman P, van Heukelem HA, Jansen JM, Visser CE, Kuijper EJ, Bartelsman JF, & Keller JJ (2008). [Treatment of recurrent Clostridium difficile-associated diarrhoea with a suspension of donor faeces]. Nederlands tijdschrift voor geneeskunde, 152 (35), 1927-32 PMID: 18808083

The long term solution for controlling cholera extends beyond antibiotics and vaccines : History books provide answers

Can cholera be eliminated?  Waldman and his colleagues, offer solutions taken from the history books, which requires sufficient investment by the global development community. We discuss their answers  - access to clean drinking  water and  safe basic sanitation. Looking at global health in general, we  discuss how this approach might  eradicate cholera and a host of other diseases that blight human health whilst alleviating poverty and ensuring sustainable development. 


Cholera, an acute intestinal infection caused by consumption of food or liquids contaminated with the bacterium Vibrio cholera, elicits the same fear today, as it did in the past. A dangerous disease, it affects children and adults, killing patients within hours. Malnourished children or HIV infected individuals are at a greater risk of death if infected. WHO figures indicate 3–5 million cholera cases per year and 100000–120000 deaths. Whilst only the epidemics, as recent as the one in Haiti in October 2010, gain notorious press coverage, it is a common occurrence in the developing world. Last October, when I visited Kerala, cholera was in the news  with confirmed cases in the state's capital.

Cholera cases in Trivandrum in October 2012 were linked to the drinking water supplied in the region.

In their recent article in NEJM, Waldman, Mintz and Papowitz cut to the chase on how cholera can be effectively controlled. Whilst giving due credit to the current developments in cholera control in the medical arena- use of  antibiotics, treatment procedure ( aggressive oral or parenteral rehydration and treatment with zinc) and  use of an improved two-dose oral cholera vaccine which had success in pilot trials, they present a lasting solution for  prevention of the disease taken from the pages of the history books. Safe sanitation and clean drinking water eliminated cholera in North America and Northern Europe and this is the route for eradication of the disease, the authors propose.

Cholera control starts with access to clean water and safe sanitation. Image courtesy Sam Stephen

However, the problem is that what  we in the developed nations take for granted-clean water and access to sanitation, is inaccessible to around 1.1 billion people globally who do not have access to improved water supply sources and 2.4 billion people  who do not have access to any type of improved sanitation facility. Guaranteeing clean water and improved sanitation is a difficult proposal complicated by a  glut of hurdles  which are technological, societal, behavioural, political and economical to name the main ones. Cholera, the authors say ‘is as much a symptom as a disease’. It is ‘a symptom of insufficient investment' by the global development community in offering access to safe water and improved sanitation for the marginalised.

The fact is that, cholera is only one of the hosts of diseases that are waterborne.  Access to clean drinking-water and sanitation are the two most powerful environmental determinants of health which go hand in hand. Take the example of diarrhoeal disease,  it is inextricably linked to waterborne infections, and is responsible for 2 million annual deaths. Babies, children and adults malnourished and with impaired immunity are particularly susceptible. Estimates indicate that 2,000 children die daily from diarrhoeal diseases, which are spread through poor sanitation and hygiene.

Hand washing instructions in a communal toilet facility in the UK. Image courtesy Sarah Stephen

The UN Committee on Economic, Social and Cultural Rights in November 2002,  on the right to water stated that “The human right to water entitles everyone to sufficient, safe, acceptable, physically accessible and affordable water for personal and domestic uses.” Universal access to sanitation is, “not only fundamental for human dignity and privacy, but is one of the principal mechanisms for protecting the quality” of water resources.Safe and clean drinking water and sanitation was declared as a human right ‘essential to the full enjoyment of life and all other human rights’ by  the United Nations General Assembly through Resolution A/RES/64/292 on 28 July 2010. Furthermore, in April 2011, the Human Rights Council adopted, through Resolution 16/2,' access to safe drinking water and sanitation as a human right: a right to life and to human dignity'.

In 2000, 189 nations made a pledge (Millennium Development Goals) to free people from extreme poverty and multiple deprivations. Goal 7, target 10 of the MDG  aims by 2015, to halve  the proportion of people without sustainable access to safe drinking water and basic sanitation. 'Safe drinking water and adequate sanitation are crucial for poverty reduction, crucial for sustainable development and crucial for achieving any and every one of the Millennium Development Goals',  a statement by Ban Ki-moon, UN Secretary General says.This goal is expedient now than ever before.

 

References:

http://www.who.int/mediacentre/factsheets/fs107/en/index.html

http://www.who.int/water_sanitation_health/hygiene/en/

http://www.nejm.org/doi/full/10.1056/NEJMp1214179?query=featured_home
http://www.who.int/water_sanitation_health/diseases/diseasefact/en/index.html
http://www.who.int/water_sanitation_health/facts_figures/en/index.html

 http://www.who.int/water_sanitation_health/mdg1/en/index.html

http://www.un.org/waterforlifedecade/pdf/human_right_to_water_and_sanitation_media_brief.pdf

http://www.undp.org/content/undp/en/home/mdgoverview.html

http://dailypioneer.com/nation/99107-cholera-makes-a-comeback-in-kerala.html

Waldman RJ, Mintz ED, & Papowitz HE (2013). The Cure for Cholera - Improving Access to Safe Water and Sanitation. The New England journal of medicine PMID: 23301693

The hidden dangers of ‘energy drinks’

‘Energy drinks’ can be harmful to the young, the old, and those of all ages with metabolic, liver and cardiovascular disorders. They could be detrimental to young adults who mix ‘energy drinks’ with alcoholic drinks. Recent articles in JAMA highlight the health issues surrounding these drinks. This blog post discusses the findings from the journal in light of the controversy surrounding ‘energy drinks’.

Energy drinks can be harmful

‘Energy drinks’ are used for increased alertness and attention skills, during a meeting, university lecture, interview, examination, or a long car drive. The most common and major ingredient of these drinks is caffeine; it may also contain sugar, cocoa, B vitamins, ginseng, liquorice etc. A series of articles in JAMA (Journal of  the American Medical Association) highlight the unseen dangers associated with energy drink consumption either on its own, with alcohol or with medications (the latter two scenarios can extend the degradation of caffeine and can magnify its harmful effects).

‘Energy drinks’ are very popular in the West and their use is on the rise. In the US, 2.3 billion ‘energy drinks’ were consumed in 2005 which rose to 6 billion in 2010.  A study indicates that it is heavily used by the US forces serving abroad, with 45% of those surveyed, reporting daily use.  More than a quarter of young teens and half of 18 to 24 year olds consume ‘energy drinks’ on a regular basis. Surveys also indicate that more than half of college students mix it with alcohol. Despite their wide usage, not all ‘energy drinks’ are the same, nor are they benign as they may appear.  Whilst some ‘energy drinks’, like most soft drinks and coffees, have about 100 mg of caffeine per serving, a few  have up to 250 mg per portion. You can access the caffeine content of various ‘energy drinks’ here. Research indicates that caffeine, whose effect has only been recently characterised, is toxic in large doses, and can even be lethal. Studies show that the likely lethal dose of caffeine is 3g.  It would require a person to consume 12 of the highly caffeinated ‘energy drinks’ in a span of few hours, to reach deadly levels in the body.

Experts believe that consumption of ‘energy drinks’ can cause increased and irregular heart rate, high blood pressure, high blood sugar, palpitations, sleep disturbances and increased urine production. ‘Energy drinks’ can be harmful for individuals with diabetes or other metabolic health problems. The combination of alcohol and ‘energy drinks’, in addition, gives further dimension to the harmful consequences, than when either ingredient is consumed alone. Caffeine disputably masks and impairs sensory clues that consumers normally use to determine the extent they are intoxicated which then could lead to risky behaviour.

‘Energy drinks’ are under scrutiny by the US Food and Drug Administration (FDA). In October last year, the FDA released a document connecting a certain energy drink to illnesses and death. Although the energy drink in question is not implicated in the cause of illness or death, it implies that a physician or family member believed that the drink could have played a role leading to an examination of this class of drinks. Whilst the drinks are being examined by the regulatory bodies, it is only wise to exercise extreme caution.

Recommendations from the scientific body

-The recommendations from American Academy of Pediatrics are that young children should not consume ‘energy drinks’ and that adolescents should restrict consumption to less than 100 mg of caffeine per day. Parents are urged to monitor the amount of consumption of beverages containing caffeine in their teenagers and help them comprehend the dangers associated with taking large amounts of caffeine.

-Torpy and Livingstone, the authors of the JAMA patient page, urge adults to limit their caffeine intake to 500 mg per day, noting that older persons may be more sensitive to the effects of caffeine. They further caution individuals with heart problems, hypertension, sleeping difficulties and those on medications to exercise caution and limit the amount of caffeine intake.

-The scientists who authored the reports on JAMA advocate for more concrete information and education about safe limits for caffeine consumption. They are calling for increased information on the effects of caffeine adolescent behaviour and development.They are urging policy makers to hold energy drink manufacturers accountable for claims regarding the health and psychosocial benefits of their products.

-The FDA’s cautionary advice to the customers is that the ‘energy drinks’ are not alternatives to rest or sleep. They emphasize that consumers should be aware that ‘though caffeine may make one feel more alert and awake, judgment and reaction time can still be impaired by insufficient rest or sleep’. They urge potential consumers to consult their health care provider to ensure that there is no underlying or undiagnosed medical condition that could worsen as a result of consuming such drinks.

References 

http://jama.jamanetwork.com/article.aspx?articleid=1487123

http://jama.jamanetwork.com/article.aspx?articleid=1487124

http://jama.jamanetwork.com/article.aspx?articleid=1487122

http://www.ncbi.nlm.nih.gov/pubmed/23134972

http://www.aap.org/en-us/about-the-aap/aap-press-room/Pages/Kids-Should-Not-Consume-Energy-Drinks,-and-Rarely-Need-Sports-Drinks,-Says-AAP.aspx

http://pediatrics.aappublications.org/content/early/2011/05/25/peds.2011-0965.full.pdf+html

http://www.guardian.co.uk/business/us-news-blog/2012/nov/15/five-hour-energy-under-scrutiny

http://www.fda.gov/Food/NewsEvents/ucm328536.htm

http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofFoods/CFSAN/CFSANFOIAElectronicReadingRoom/UCM328270.pdf

http://onlinelibrary.wiley.com/doi/10.1111/j.1541-4337.2010.00111.x/full