Continuing along in this theme.

People who have travelled to areas of the world with high rates of antibiotic resistant bacteria such as South Asia and the Middle East are more likely to carry superbugs, a new study has found.

Do read the article "Tourism spreading antibiotic resistant superbugs new study reveals" in the The telegraph from March 5, 2018. www.telegraph.co.uk/news/2018/03/05/tour...s-new-study-reveals/

The article is based on a report from Univ of Birmingham academic.oup.com/jac/advance-article/doi...85410?searchresult=1 but I think the journalist Madlen Davies wrote a much more compelling story.

Regards

Further to this topic. There have been over the past year or so several papers and illustrative communications on the topic.

The cartoon: The Antibiotic Apocalypse (by Kurzgesagt in Munich and supported by BMGF)
www.fastcoexist.com/3058039/this-animate...ntibiotic-apocalypse
explains the influence of overuse of antibiotics in both humans and animals. Direct link to the video:




The cartoon explains the origin of the problem but doesn't include the aspect of sewage systems as vector for spreading the plasmids and genomes. It does implicate faecal-oral transmission combined with global transportation.


Development of AMR in sewage treatment plants has been shown at least in one recent (2015) study to be insignificant. The title of the paper I find somewhat misleading: "Wastewater treatment plants not responsible for spreading antimicrobial resistance" by Technical University of Denmark (DTU)
www.sciencedaily.com/releases/2015/10/151007084248.htm

This paper I find confuses the issue. I don't think it is common knowledge that AMR is being created in the activated sludge of treatment plants. AMR develops in the guts of humans and animals as well explained in the video above.

And sewage systems can be vectors in the spread of AMR plasmids and genomes. That is the issue of major significance.

This illustration (from Schmieder, R. and Edwards, R. 2012. Future Microbiol. 7(1): 73.81) is of fundamental value, showing the various vectors:



At this point what is needed is further emphasis on screening and epidemiology. But we need to be able to reduce the risk of spreading these AMR agents. Sewage systems therefore need to be counted in as significant vectors not only as vectors for spreading AMR but for the multitude of viral and bacterial infections that exist. Faecal-oral transmission is well-established. Question is whether the risks are reduced by flushing away faeces into sewer systems not designed to block transmission.

Marijn

Tsunami yes but it has been very slow in its development. The evidence was out and in publications 3-4 years ago as I wrote a few years back. See forum.susana.org/forum/categories/26-hea...mit=12&start=12#2758

Good to see there is better understanding about the need for containment and treatment of sewage. Could be that doctors and pharmaceutical companies will understand now that overzealous use of antibiotics can have global impacts at a scale of a Tsunami wave of incurable inestinal infection. And that medicine needs to start including sanitation systems in its realm of central concerns.

Regards

We're mixing waste with water and then mixing microbes, allowing horizontal gene transfer creating antibiotic resistant organisms. Then poor sanitation and agricultural practices allow these organisms access to our bodies. They enter our bodies through food, water and air, overgrowing in places such as the small intestine where they don't belong and there's no competition for them. This leads to malabsorption syndrome and weakened immune systems such that vaccination fails as vaccines rely on a balance of flora to stimulate immune response. Our immune systems are a reciprocal relationship between microbes and host.

So, we may minimize OD while still fostering antibiotic resistance. OD isn't the main origin of the problem. We need to develop waste processing systems that don't select for antibiotic resistant organisms via killing their competition. But how can we mitigate horizontal gene transfer between organisms?

"Nonetheless, much remains to be learned about how to prevent acquisition and transmission of resistance."
Antibiotic Resistance — Problems, Progress, and Prospects
www.nejm.org/doi/full/10.1056/NEJMp1408040

Trend is to promote probiotics instead of antibiotics:
Probiotics as a Strategy to Improve Overall Human Health in Developing Countries
omicsonline.org/open-access/probiotics-a...000118.php?aid=32517

Phage therapy (use of viruses) along with probiotics:
Assessment of synergistic combination potential of probiotic and bacteriophage against antibiotic-resistant Staphylococcus aureus exposed to simulated intestinal conditions
link.springer.com/article/10.1007%2Fs00203-014-1013-z

Essay about using probiotics to combat antibiotic resistance:
Probiotics and Antibiotic-Associated Diarrhea
www.klaire.com/images/probioticsantibiotic.pdf

Further to the NY Times article, Sanjay Wijesekera, Chief of Water, Sanitation and Hygiene, and Associate Director of Programmes at UNICEF blogged on 5 Dec in Huffington Post, under the caption of “The Road to Health Goes Through the Toilet,” and has given interesting figures.

www.huffingtonpost.com/sanjay-wijesekera...oes-t_b_6278246.html

He says: “India has the highest level and number in the world of people who do not use toilets. Some 597 million people, or roughly 50 percent of the population, according to UNICEF and WHO's latest estimates, defecate in the open.”

I was under the impression that percentage of India’s population, resorting to OD is around 40. He has also given some statistics of other countries – interesting reading. According to him:

“The open defecation problem has got better in the world, but in 26 sub-Saharan countries in Africa, the numbers of people who defecate in the open are increasing. India and nine other countries make up 82% of the 1 billion people in the world who practice open defecation. The others are, in millions: Indonesia (54), Pakistan (41), Nigeria (39), Ethiopia (34), Sudan (17), Niger (13), Nepal (11), China (10), and Mozambique (10).”

On "superbugs" -- antibiotic-resistant infections in India, he says:

“People living in India are more prone to bacterial infections because -- due to open defecation -- the places where they walk, the water they drink, the food that they eat, is more likely to be contaminated with fecal matter. To address the infections, and other fecal-oral illnesses, doctors give them antibiotics. And then the infections become antibiotic-resistant. This is very dangerous to all, and particularly to children.”

It is appalling that doctors in India give antibiotic to the newborns. In Pakistan, antibiotics are freely used – no doctor’s prescription is required. Antibiotics are used by those who are infected and down with fever. But, generally, doctors do not prescribe antibiotics to newborns, unless there is some specific need.

While India is trying hard to end OD, it would be years before OD problems are minimized. Till then, the large-scale use of antibiotic will continue to be major problem for India.

F H Mughal


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Note by moderator: in response to this post by Mughal (and in particular in response to his sentence "While India is trying hard to end OD, it would be years before OD problems are minimized"), a new thread was started here:
forum.susana.org/forum/categories/142-up...o-be-minimised#11288

Giacomo, thanks for posting the NYT article, indeed frightening. Also important to note the superbugs are thought to pass from mother to newborn infant, a matter of microbial predisposition (my own term). This is truly a generational issue.

And we can't simply throw WWTPs at the problem, as wastewater is a known breeding ground for superbugs. Key is to keep waste out of water.
www.nature.com/ismej/journal/v8/n7/full/ismej20148a.html
www.medscape.com/viewarticle/756378_8
pubs.rsc.org/en/Content/ArticleLanding/2...m00208c#!divAbstract
www.plosone.org/article/info%3Adoi%2F10....journal.pone.0078906

And, in my opinion, this problem of poor microbial predisposition results in increased vaccine injuries:
www.greenmedinfo.com/blog/vaccine-injury...obial-predisposition
www.greenmedinfo.com/blog/critical-role-...flora-vaccine-injury


+++++++++++

Note by moderator (EvM):

Just to avoid that we repeat too much a discussion we have already had:
See here for a discussion on the role of wastewater treatment plants and antibiotics resistance:
forum.susana.org/forum/categories/26-hea...age-and-water-supply

See here for a discussion about the vaccine injuries topic:
forum.susana.org/forum/categories/26-hea...-various-discussions

If anyone has more to add on those topics, please add them in those threads, keeping in mind that a general debate on vaccinations "yes or no" is not within the scope of this forum (see Rule 8 here: forum.susana.org/forum/rules)

"Unintended consequences"

"Collateral damage"

These are terms we hear (and deplore) when talking about war activities from developed nations.

We never hear the terms applied to the hordes of well-meaning NGO's, donors and agencies who are out there to do good.

But maybe we should; maybe we need to have a form of Environmental Impact Assessment (a Community Impact Assessment or something) that project promoters have to conduct before they launch their next "wonderful thing" on an unsuspecting world.

The cheap medicine bandwagon has been going on for years now, but if the results are highly antibiotic resistant bugs (which are not just a developing country problem, as you can see from the deaths in hospitals stats in every country, developing or developed), then certainly it's time to review the whole management issue/.

But I feel that part of the problem is money: it's easier and cheaper to just push a centralised drug manufacturer or a small number to pump out the cheap drugs (they still make a profit) than to solve the sanitation problems at source.

Maybe we need to provide a system where users have to prove they have adequate sanitation and hygiene facilities (and, of course the access to sanitation and hygiene mechanisms to make sure everybody can have them) as part of the trade off for free / cheap medicines?

It's a little simplistic but I do think that somewhere between "free & unconditional access" to benefits such as low cost medicines, and personal & community responsibility to protect yourself and the community, may be the right balance

Interesting that 2 of the articles use the image of a Tsunami.

But that was an aside, I think a large part of the problem in South Asia is the fact that antibiotics are sold over the counter for cheap, without any prescription or instructions.

To re-supply our stocks, I recently bought 40 tablets of 500 mg Ciprofloxacine and 60 tablets of 400 mg Metronidazole for the grand price of 4 US$.

On the one hand it is great that poor people can get these medicines at an affordable rate, but there is absolutely no education. For example, some of my quite well educated Nepalese colleagues, will take 1 or 2 tablets of Metro to get rid of some mild stomach problem. And maybe 1 table the next day if complaints persist.

It is not only bacteria either, last year I had a multi-resistant strain of Giardia after a visit to India.

I don't want to say that sanitation is not an important link in this problem, but it is more complex than just blaming the lack of toilets. This should really be an issue, where different sectors in development join (washed) hands.

Marijn

Hi all,

Interesting article in the NYT on how antibiotic resistance is growing especially in India, resulting from a large use of antibiotics and low levels of sanitation.

www.nytimes.com/2014/12/04/world/asia/su...hreat.html?ref=world

“India’s dreadful sanitation, uncontrolled use of antibiotics and overcrowding coupled with a complete lack of monitoring the problem has created a tsunami of antibiotic resistance that is reaching just about every country in the world,” said Dr. Timothy R. Walsh, a professor of microbiology at Cardiff University.

It seems that the 'easy solution' of providing ever more antibiotics instead of tackling the root causes of poor sanitation, is starting to backfire. What are your thoughts on this?

Best,
Giacomo

Thanks for sharing this article.

Not 100% related, but maybe we could use this to start a discussion on effects/problems of antibiotic use in EcoSan?

For example livestock antibiotic use can be a real problem in biogas digesters fed with manure, especially if you collect it from various sources and don't always know if the farmer might have used them to treat the animals.

But also see here: www.biofermenergy.com/improving-public-h...-with-a-biodigester/
(I wonder if the fate of resistance genes has been studied in livestock fed digesters)

Similarly I wonder what effects antibiotics could have on composting processes.

At least it seems like composting can remove a lot of antibiotics from the fecal sludge/manure, see a recent study on chicken manure:
www.ncbi.nlm.nih.gov/pubmed/23384781

Never the less, it could be that EcoSan nutrient cycling could also have the negative side effect of antibiotic resistance gene cycling, if treatment is incomplete or inefficient (mesophilic anaerobic systems?) it might facilitate the spread of them back into the general population.

Any thoughts or links to good studies on this?

Edit: google brought up this:
www.ncbi.nlm.nih.gov/pubmed/24374028
www.ncbi.nlm.nih.gov/pubmed/23607603

Edit2: Here is a good overview article that isn't behind a paywall:
ehp.niehs.nih.gov/1206446/
Excerpt:

Management of manure containing antibiotics.
Composting eliminates on average 50–70% of some antibiotics (Sharma et al. 2009; Storteboom et al. 2007; Wang et al. 2012; Wu et al. 2010). Antibiotic degradation is suspected to primarily occur only during the thermophilic phase over the first 2 weeks, and efficiency depends on both duration and temperature. Storteboom et al. (2007) observed that watering, aeration, and turning of compost offered some advantage to accelerating antibiotic decay of chlortetracycline, monensin, and tylosin, but even simple storage of manure stockpiles resulted in significant antibiotic degradation. Digestion of livestock waste can also treat antibiotic residues; 5-week fermentation effectively removed most sulfonamides and trimethoprim (Mohring et al. 2009), whereas sulfamethoxazole and oxytetracycline were reduced more effectively under aerobic than anaerobic incubation of dairy lagoon water (Pei et al. 2007).

Biological treatment of ARGs in manure.
Response of ARGs to biological treatments, such as lagoons and composting, varies because of the complex microbial ecology involved. Composting and manure storage resulted in up to 100-fold reduction of tetracycline ARGs, but tet(O) increased when horse manure was composted, even in the absence of measurable antibiotics (Storteboom et al. 2007). Persistence of ARBs (such as Escherichia coli) and ARGs [tet and erm (erythromycin resistance methylase)] has been observed after composting (Sharma et al. 2009), and ARGs can persist even in the absence of selection pressure (Johnsen et al. 2011). McKinney et al. (2010) observed up to 10-fold reduction of tet ARGs across six anaerobic livestock lagoons monitored, but sul ARGs tended to increase with treatment time. Other researchers have reported lagoon treatment to be less effective than composting (Wang et al. 2012). A recent laboratory study with an agricultural E. coli strain suggested that anaerobic treatment may be a promising way to impose a high metabolic burden on bacteria and thus limit their capability to engage in horizontal gene transfer (Rysz et al. 2013).

(...)

Wastewater reuse.
Wastewater reuse is becoming a worldwide strategy for water sustainability. However, it is critical to carefully evaluate the application of reclaimed water and establish proper safeguards in order to avoid unintended consequences. It is common practice to employ different treatment levels for different purposes (e.g., bathing vs. toilet flushing or irrigation). Wastewater is commonly disinfected via ultraviolet radiation or chlorination, which may kill resistant bacteria, but ARGs are more recalcitrant (Auerbach et al. 2007; Kim et al. 2010; McKinney and Pruden 2012; Munir et al. 2011). Li and Zhang (2012) reported that chlorination reduces several antibiotics, including ampicillin, chlortetracycline, sulfamethoxazole, sulfadiazene, ofloxacin, and trimethoprim. Ozonation has been reported to efficiently reduce a broad range of antibiotics and their active metabolites (Dodd et al. 2010).

Sludge/biosolids and other solid wastes.
Land application of sludge/biosolids from WWTPs, another means of resource recovery, also serves a second purpose: disposal of a costly treatment by-product. However, ARBs and ARGs are known to be present in biosolids (Brooks et al. 2007; Munir et al. 2011). Research suggests that culturable heterotrophic ARBs attenuate quickly after amendment to soil (Brooks et al. 2007), but studies employing culture-independent techniques indicate otherwise. For example, in a recent study comparing land application of manure versus biosolids, Munir and Xagoraraki (2011) found elevated levels of tetracycline and sulfonamide ARGs in soils amended with biosolids during the 4-month monitoring period. Interestingly, the effect was more strongly driven by soil characteristics than by the source. Munir et al. (2011) also noted that among five U.S. WWTPs, the loading rate (mass × concentration) of tetracycline and sulfonamide ARBs and ARGs produced in biosolids was ~ 1,000 times higher than that in aqueous WWTP effluent.

I recently came across this article in Nature magazine (thanks to someone's recommendation on Twitter) which points to lack of sanitation being one likely culprit to antibiotic resistance sweeping the developing world and in particular the countries in transition (see also a previous related discussion here on the forum: forum.susana.org/forum/categories/26-hea...age-and-water-supply):

www.nature.com/news/antibiotic-resistanc...loping-world-1.15171

I copy here some sentences that I found very interesting:

Antibiotic resistance sweeping developing world

Bacteria are increasingly dodging extermination as drug availability outpaces regulation.

By most standards, the increasing availability of life-saving antibiotics in the developing world is a good thing. But, around the globe, overuse of these drugs has created resistant strains of deadly bacteria — and they could be a greater threat in poorer nations than in richer ones, owing in part to a lack of regulation.

[...]
The problem also seems to be particularly acute in the emerging economies known as the ‘BRIC’ states: Brazil, Russia, India and China, says Keith Klugman, an epidemiologist for the Bill & Melinda Gates Foundation in Seattle, Washington.

[...]

As a result, researchers do not know what factors have caused resistance to grow so rapidly in developing nations. For instance, it is not clear to what extent the rise of resistance has been spurred by the use of antibiotics for growth promotion in livestock, or by the release of antibiotics into wastewater by drug-manufacturers in countries such as India.

One likely culprit is a lack of sanitation. In many areas, wastewater from hospitals is poorly filtered, allowing the antibiotic-resistant bacteria that flourish there to escape into waterways. If people drink this contaminated water or practise poor hygiene, the bacteria can spread. “If you get increased antimicrobial use but don’t have the infrastructure for infection control, you’re setting yourself up for a tsunami of antibiotic resistance,” says Klugman.

I find the article well written, and the facts scary... The only "good" thing that might come out of all this mess is more attention and funding to sort out lack of sanitation (including poor wastewater treatment) in those countries in transition (mainly India, but also Brazil, Russia and China).

Regards,
Elisabeth