Clostridium perfringens spores under the microscope. Photo by Don Stalons of CDC.

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

What is Clostridium perfringens?

Clostridial diseases are classic in medicine, both veterinary and human. It is a Clostridium that causes tetanus and 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 it can produce are called enterotoxins. We are particularly concerned about the alpha, epsilon, and net E/F toxins. These toxins can be seen in normal dogs, but if they are in high enough amounts, they are associated with diarrhea.

How Would Clostridium perfringens Infection Happen?

In order to produce toxin(s), the organism must form a spore (sporulate). 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 up rotten dead things, etc.

When the organism arrives in the small intestine, it 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 to sporulate and produce toxin.

The trigger may be dietary, may be related to infection with another organism, or may even be related to medications, especially antibiotics. The type of diarrhea produced is generally a colitis, meaning the large intestine is affected. Such types of diarrhea are mucousy, possibly bloody, and associated with straining. More watery diarrhea, as comes from the small intestine, is also possible. The severity of the diarrhea can range from mild to life-threatening, depending on how much toxin is produced. The important concept is that C. perfringens toxin can be the cause of chronic diarrhea, or it can be a complicating factor in diarrhea caused by something else.

Can we Test for Toxin-Producing Strains Of Clostridium perfringens?

The culture will not tell us if the strain present can produce the enterotoxin. Clearly, we need to know more than whether there are any C. perfringens. How about culturing for Clostridium perfringens? Again, cultures are not very helpful. Clostridium perfringens can be cultured from the feces of 80% of dogs, whether they have diarrhea or not. Some dogs seem to be unaffected.

This is where PCR testing comes in; it is a form of DNA testing whereby the C. perfringens are tested for the DNA needed to make the different enterotoxins. In this way, we can detect the genes that are capable of producing enterotoxin. Furthermore, the number of gene copies can be measured so that we can tell if there are large or small amounts of toxin genes. Large amounts of toxin genes are associated with disease, so 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 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 that not only are there large amounts of toxin genes, but they are confirmed to be producing toxin.

The severity of the diarrhea can be mild all the way to life-threatening.

When Should We Treat for Clostridium perfringens?

Let's begin with the obvious: a pet does not need to be treated for C. perfringens unless he 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 of significant amounts of Clostridial genes capable of producing toxin. And all this must be found in a patient that actually has diarrhea.

The chances are that a fecal check for worms has been done, and a trial course of an anti-diarrheal medication has been tried. A possible next step would be a PCR panel that detects the DNA from an assortment of viruses and bacteria 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 significant Clostridial diarrhea thus might yield only partial results.

Treating the Toxin-Positive Dog with Diarrhea

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