CLOSTRIDIUM PERFRINGENS

When pets get chronic diarrhea, one of the tests that sooner or later comes up is the test for Clostridium perfringens enterotoxin. Clostridium perfringens is a bacterium and it produces an unpleasant toxin. The situation sounds simple: one gets infected with toxin-forming bacteria, one gets diarrhea, the diarrhea should at least improve with removal of the toxin-forming bacteria. As with most things, the situation turns out to be more complicated.

Clostridium perfringens spores under the microscope
(Photocredit: CDC Public Health Image Library)

What is Clostridium perfringens?

Clostridium perfringens is one species out of numerous Clostridia. Clostridial diseases are very classic in medicine, both veterinary and human. It is a Clostridium that causes tetanus, a Clostridium that causes botulism, and Clostridia are responsible for gangrene, “black leg,” lamb dysentery and other famous maladies. Clostridia have several features in common that make them especially nefarious but most importantly:

• They produce toxins.
• They are anaerobic (they grow in the absence of oxygen).
• They form spores (essentially armor) so as to withstand environmental change (including disinfectants) that would kill more vulnerable bacteria.

Clostridium perfringens is one of the brothers of the evil Clostridium family but is further classified into five Biotypes (A, B, C, D and E) depending on what combination of four toxins it produces. Dogs are almost exclusively infected with Biotype A.

The toxins of significance that Clostridium perfringens can produce are called enterotoxins. We are particularly concerned about the "alpha" toxin, the "epsilon" toxin, and the "net E/F" toxins. These toxins can be present in normal dogs but if they are present in high enough amounts, they are associated with diarrhea.

How would Clostridium perfringens infection happen?

In order to produce toxin(s), the organism must sporulate (form a spore). Before it can do that, it must make its way into the host's intestine from the outside world.

The organism enters the body orally: in food, grooming of fur, chewing carrion etc. When the organism arrives in the small intestine, it sporulates (forms a spore) and begins to produce its toxin(s). Alternatively, the organism may have been happily and innocuously living in the intestine for who knows how long when something causes it sporulate and produce toxin. The trigger may be dietary, may be related to infection with another organism or may even related to the administration of medications (antibiotics especially). The type of diarrhea produced by the toxin is generally a colitis, meaning the large intestine is affected. Such types of diarrhea are mucous, possibly bloody, and associated with straining. A more watery diarrhea (as comes from the small intestine) is also possible. Severity of the diarrhea can be mild all the way to life-threatening depending on how much toxin is produced.

The important concept is that Clostridium perfringens toxin can be the cause of the chronic diarrhea or it can be a complicating factor in a diarrhea caused by something else.

Can we test for toxin-producing strains of Clostridium perfringens?

In the past, looking under the microscope for Clostridial spores was thought to be helpful, since we know the organism must change to its spore-form to produce toxin. Apparently, the organism may sporulate innocuously without producing toxin so this method has not been as helpful as we had hoped. Clostridium perfringens can be cultured from the feces of 80% of dogs whether they have diarrhea or not. The culture will not tell us if the strain present can produce the enterotoxin. Clearly we need to know more than whether there is Clostridium perfringens present. This is where PCR testing comes in. PCR testing is a form of DNA testing whereby the Clostridium perfringens present are tested for the DNA needed to make the different enterotoxins. In this way, we can detect the genes that are specifically capable of producing enterotoxin. Further, the number of gene copies can be measured so that we can tell if large amounts of toxin genes are present or if small amounts are present. Large amounts of toxin genes are associated with disease so that in this way we can tell if one of the Clostridium perfringens enterotoxins is likely to be contributing to the patient's diarrhea.

There is also a test for the toxin but it is of an ELISA format which means it is either negative or positive and does not say how much or how little toxin is present. In a perfect world, this test is combined with the test for the toxin producing genes so as to confirm, not only are large amounts of toxin genes present but they are confirmed to be producing toxin.

When should we treat for Clostridium perfringens?

Let us begin with the obvious: a dog does not need to be treated for Clostridium perfringens unless it has diarrhea. Since 80% of dogs harbor Clostridium perfringens whether they have diarrhea or not, culturing Clostridium perfringens from a fecal sample will not be adequate for diagnosis; we have to find the toxin or, at the very least, verify the presence significant amounts of Clostridial genes capable of producing toxin.

So going back to the patient, dog or cat, with chronic diarrhea. Chances are that a fecal check for worms has been done and a trial course of an anti-diarrheal medication has been done. A possible next step would be a "PCR panel" that detects the DNA from an assortment of viruses and bacteria that are associated with diarrhea. Often this type of panel includes a test for Clostridial enterotoxin DNA. The laboratory will report a quantification of gene copies for CPA (the gene for the alpha toxin), CPE (the gene for the epsilon toxin), and CP net E/F (the gene for the net E/F toxin). If the number of toxin genes for any of these toxins is significant, treating with antibiotics against Clostridium is indicated.

Keep in mind that Clostridial diarrhea might be the entire problem and curative with the right antibiotic or it might be secondary to a bigger problem yet to be discovered. Treatment for a significant Clostridial diarrhea might thus yield only partial results.

Treating the toxin positive dog with diarrhea

Any number of antibiotics can be used to remove Clostridium perfringens. Some choices include: ampicillin, amoxicillin, metronidazole, erythromycin, and tylosin. Tetracycline was formerly on the list but too much resistance has developed. If Clostridium perfringens is responsible for the diarrhea, a response to antibiotics is generally seen in a couple of days but the full course of medication should still be completed.

 Page last updated: 6/29/2021