homeopathy replacing antibiotic? Oy vey!

Enteropathogenic Escherichia coli is a common etiological agent of enteric diseases of young piglets. E. coli attaches to intestinal villi using surface protein adhesins, and subsequently colonizes, and proliferates in, the anterior small intestine; the production of enterotoxins results in clinical disease. The diseases manifest in two ways:

1. The enterotoxin causes extrusion of fluid into the gut lumen leading to colibacillary diarrhea, which occurs neonatally upto weaning
2. Enterotoxemic colibacillosis, which occurs during weaning and is not always accompanied by diarrhea.

The E. coli strains producing enterotoxins may also penetrate the cells of intestinal epithelium, resulting in hemorrhagic diarrhea with systemic toxemia, and may exhibit varying susceptibility to a variety of antibiotics.

E. coli disease is a significant problem in the swine industry, resulting in diarrhea, increased mortality of neonatal piglets, and poor growth and performance in the weanlings. Traditionally, this is controlled by addition of sub-therapeutic levels of antibiotics in the feed. However, the emergence of multi-antibiotic resistant bacterial strains in animal husbandry and subsequent risks to human health are major concerns which have spurred research in elimination of in-feed antibiotics and use of various feed supplements. A successful approach has been to vaccinate pregnant sows with purified adhesins as antigens, which has been shown to confer substantial protection to the litters born to them – in terms of mortality, reduction in diarrhea and fecal excretion of E. coli strains.

To make a clear distinction at this point, we are not talking about post-weanlings, who get their individual feeds and will have established their own gut microflora. Gut micro-organisms, which are diverse and some of which haven’t been cultured, play a central role in the resistance to disease. The focus of this post is colibacillary diarrhea in neonatal piglets which suckle colostrum, rich in maternal antibodies, from their mothers.

One may well ask why on earth this is the focus of this post. Simply put, it is because this neonatal piglet model has been used in a recent research paper from the Netherlands to tout homeopathy as a replacement to antibiotics in E. coli diarrhea (Camerlink et al. “Homeopathy”, Volume 99, Issue 1, pp. 57-62, January 2010; Special Issue: Biological models of homeopathy Part 2; Eds. Baumgartner et al., published by Elsevier) (If anyone wants the PDF, please ask me).

Let that sink in a moment: homeopathy as a replacement to antibiotics. And let me tell you the result of this study beforehand; I promise, it will not spoil the mystery. The authors concluded that piglets from sows treated with the “homeopathic agent Coli 30K” had significantly less E. coli diarrhea than those from sows in the placebo group. No surprise there, right? The authors also mention –

[I quote] The diarrhea seemed to be less severe in the homeopathically treated litters, there was less transmission and duration appeared shorter.[End quote]

Note the gratuitous use of the weasel-words. You know what they are. No mystery there.

To commence, I am going to ignore most of the introduction, and merely leave you with two laugh-riot-inducing statements therein.

[I quote] Homeopathy has demonstrated in many medical areas its effectiveness in practice, but scientific evidence is lacking. [End quote, emphasis mine]

Their words. And yet, they claim without any qualm,

[I quote] Homeopathic remedies have significant benefits since there are no residues in animal products, nor does homeopathy generates resistant micro-organisms. [End quote]

And, of course, there is the trademark special pleading.

[I quote] Many experiments in the homeopathic field have failed to prove an effect of the treatment. Reasons for that could lie in the methodology of medicine testing as applied in regular medical science, which partly contradicts with the homeopathic philosophy. [End quote]

But let’s dive into the meat (broccoli, for the vegetarian amongst us) of the experiment – materials and methods, and results. Let me draw your attention to several points, the significances of which will be clear anon.

1. Experiments were carried out in normal farm conditions, “according to homeopathic principles of disease and recovery” [author quote].
2. Piglet mortality on the farm —where the experiment was conducted— was 12.1% in 2008, partly caused by neonatal E. coli diarrhea. – The experiment appears to have been conducted in non-sterile, non-sanitary, uncontrolled conditions where there may be potential confounders, skewing the outcome one way or another. On the other hand, with close to 88% of piglets not being affected by colibacillary diarrhea, I sure hope they have a strong model of infection/colonization to test with their therapy – particularly since they appear not to know if and how much E. coli is responsible for their annual piglet mortality.
3. Fifty-two healthy sows in their last month of gestation, no prior vaccination against E. coli, were selected; however, there was no evaluation of their eminently possible, casual exposure to E. coli in the farm.
4. Sows were assigned to batches depending upon expected week of parturition, and strata were made for parity (first or >1). It has been shown (Nielsen et al., 1968, J Am Vet Med Assoc, 153:1590) that age of the mother may influence the susceptibility of the neonatal piglet to diarrhea, in that piglets from younger pregnant sows (called “gilts”) were more vulnerable to E. coli diarrhea than those from older sows. – Unless the homeopathic nostrum was designed to magically have some vaccine-like effect and actually produce antibodies to E. coli, this kind of grouping was completely irrelevant, unnecessary and inconsequential. The authors were blindly following the protocols in an E. coli vaccine paper, but didn’t put any further thought into the methodology.
5. The animals were not deliberately infected, nor was the treatment performed at a random farm but in a situation where E. coli occurred naturally: – So, there was no experimental infection model, and no standardized inoculum based on which the therapeutic outcome could be assessed. The “experiment” was left at the mercy of providence and wishful thinking that somehow “natural” E. coli would cause disease. Well, did it? We shall see soon.

Let us turn our attention to the “treatment” protocol now. The homeopathic agent Coli 30K is a ‘nosode’ prepared from various strains of E. coli bacteria. For the uninitiated, nosode means a homeopathic nostrum derived from disease material (e.g. discharges, tissues, secretions, excretions – ewww!) and passed though the so-called potentization process. This specific nosode was prepared from various strains of E. coli, and consisted of 99.85% demineralised water, 0.1% pure alcohol and 0.05% milk sugar sprinkled with a homeopathic potentization of E. coli. The placebo had exactly the same content, except for the potentized E. coli. The treatment was administered by spraying the agent in the vulva of each sow, twice a week during the last four weeks pre-partum. If I were to conduct this experiment, I would make sure that the “potentized” preparation didn’t have any live bacteria – a simple culture would do. But the paper is silent on this.

Of note is that the culture of fecal samples from the litters failed to yield any enteropathogenic E. coli or for that matter, Salmonella. Ordinarily, one would conclude that the litters did not have colibacillary diarrhea, which stands to reason, because

• The virtually infinitely diluted nosode is not expected to contain any live bacteria
• Even if there were any viable organism left, spraying on the vulva (!) would not carry the bacteria to the gut lumen to cause attachment, invasion, colonization and disease. (Methinks someone needed a basic anatomy lesson before planning experiments; I don’t know if they teach that in quack schools)

But when homeopathy is concerned, is anything ordinary? Therefore, experience this mind-boggling whopper.

[I quote] This does not per se demonstrate that enteropathogenic E. coli were not present at the farm at that moment. It was a relatively small sample size of three litters, which would not necessarily include the infective agent. [End quote]

What prodigious hand-waving! But that’s not all, folks. How do they know it was colibacillary diarrhea?

[I quote] Because treatment with Coli 30C had worked before, and E. coli diarrhea generally can be distinguished based on day of appearance and colour, this was not further investigated… Scours from E. coli bacteria were distinguished on the basis of colour and day of appearance. [End quote]

Gigantic FACEPALM!

So… because their lab tests did not show any evidence of colibacillary diarrhea, they just literally made shit up!

I should have stopped reading this paper at this point, but I went ahead with a kind of horrified fascination.

Hoping for more fun, I now pored through the results section. The first thing that struck me was that the sizes of study samples and outcomes. The authors keep mentioning big numbers, but in reality, there were 525 total piglets in the study (265 born to placebo-receiving sows, and 260 born to homeopathically treated sows). Of these, only 88 piglets contracted diarrhea, but 15 of them were excluded because they did not fit the definition of E. coli diarrhea, based on day of appearance and colour. Not only it’s not mentioned which group these 15 belonged to, but the endpoint/outcome of diarrhea was observed in only ~14% (73/525) of piglets.

In Table 2, the authors show E. coli diarrhea (assuming it was) in 63 piglets of the placebo group and 10 in the Coli 30K group, calculating a percentage against total numbers in the groups. But given the low rate of natural infection, lack of experimental infection and lack of culture-confirmation of colibacillary diarrhea, how many of these piglets were actually at risk for diarrhea? This is a major factor that would obviously influence the outcome of the experiment.

As shown in Table 3, none in the Coli 30K group, and 17 in the placebo group, contracted diarrhea in less than a day. On the other hand, on day 1, 4 and 5 the proportion of occurrence of diarrhea is much higher in the Coli 30K group. But the significance of these proportions, analyzed post-hoc, is doubtful, since the group sample sizes are so disparate (63 vs. 10). Counting “duration” from the day of appearance of diarrhea until normal feces or death, authors claim that average duration of diarrhea tended to be longer in the placebo group, but all Coli 30K group piglets had diarrhea for 1-3 days and there is no indication whether they died or lived thereafter. In contrast, more than 20% of the placebo group had chronic (>4 days) diarrhea, with which they survived at least that time period. Mean duration of diarrhea was not significantly different between the groups.

In addition, a simple serological analysis of the sow and the piglets would have sufficed to show if there were E. coli positive (e.g. K88⁺) antibodies in the serum, which would indicate prior or casual exposure (which would be natural in the farm). But it was not tested: So it is unclear whether or not the neonatal piglets, sucking colostrum from the mother, were in fact getting enriched with pre-formed maternal antibodies to E. coli (which takes approximately only 12 hours to complete), particularly those that didn’t have diarrhea. Obviously, this would affect the outcome of the experiment.

Clearly, no definitive conclusion about the triumph of the homeopathic nostrum can be drawn from these set of numbers from a single experiment, especially one which appears to be ill-conceived and badly-executed, without a consistent animal model and a positive control, and where observed differences with placebo are, at best, questionable. Perhaps the authors recognize this, when they acknowledge that [I quote] “Independent repetition on different farms with standard preventive treatment against E. coli is required.” [End quote]

I, meanwhile, am not holding my breath.

Camerlink, I., Ellinger, L., Bakker, E., & Lantinga, E. (2010). Homeopathy as replacement to antibiotics in the case of Escherichia coli diarrhoea in neonatal piglets Homeopathy, 99 (1), 57-62 DOI: 10.1016/j.homp.2009.10.003