Co-infections have major influence on infectious diseases

Animals are infected by more than one infectious agent at a time in natural settings. Thus, co-infections are the norm rather than the exception.

However, since the scientific revolution that tied microscopic infections to disease — the “germ-theory” of disease — most re-searchers have focused on one pathogen infection at time.

This was a reasonable approach because it is challenging enough to understand how a single pathogen works to make animals sick.

However, it also means that this simplified approach may overlook a key factor.

There is growing evidence that multiple infections can have a profound impact on the dynamics of infectious diseases.

When it comes to co-infection scenarios, we know the most about the interplay of nematode worms and microscopic organisms.

Worms influence the immune system in ways that can affect the outcome of bacterial and viral infections. They also change how animals respond to clinical diagnostic tests.

Some researchers have even suggested that we consider worms as a normal part of an animal’s internal ecosystem, along with the beneficial bacteria and other microscopic organisms.

Worm parasites may have played a crucial role as immune system regulators during the evolutionary process. In particular, worms dampen immune responses to viruses, bacteria and the body’s own cells.

They do this by shifting the immune system from its reactive mode, which fights off bacteria and viruses while causing severe tissue damage, to the mode responsible for healing and tolerance.

It is often the immune responses to viral and bacterial infections that lead to disease rather than the direct damage of the pathogen itself.

When it comes to the body’s response to infection, the Goldilocks Principle applies. Too much or too little can be significantly harmful to animals; it needs to be just right. Worms seem to have this modulating effect.

The growing knowledge about the interplay of worms and the immune system has contributed to another important disease theory, the so-called “hygiene hypothesis.” It poses that autoimmune diseases and allergies arise in humans and animals that are too “clean” and parasite free.

Because most people, dogs and cats in developed countries are worm-free, the immune system can ramp up and even go overboard. These over-zealous immune reactions are thought to be major contributors to diseases such as canine atopy.

In people, there is some evidence that intentional infections with gut worms can moderate autoimmune diseases such as inflammatory bowel disease and even multiple sclerosis. Treating horse, dog and cat allergies with worm infections may not be far behind.

In addition to immune system effects, worms can alter the reliability of disease diagnostic tests.

Researchers at the University College in Dublin, Ireland, have investigated this problem by studying the relationship between liver fluke infections and bovine tuberculosis in cattle.

Both fluke infections and bovine TB are major issues for cattle health in that country and around the world.

A key discovery was that fluke-infected cattle had false negative tests for TB. Cattle that should have “reacted” to the caudal fold test were negative, likely because of the presence of liver flukes. This effect was especially problematic when fluke infections were established before the TB exposure.

A field study supported this result by confirming that fluke-infected cattle were less likely to test positive for TB.

Overall, this result may mean that false negative results because of fluke infections could hamper TB eradication efforts. Further studies are needed to know whether treatment for flukes will help the reliability of TB tests in cattle.

It would also be interesting to know how worms such as liver flukes affect disease outcomes and tests for Johne’s disease and other cattle pathogens.

The advent of powerful computers to analyze complex data and molecular tools to diagnose previously unidentified pathogens has greatly advanced our understanding of co-infections in animals.

A deeper understanding of co-infections may have important implications for animal health, and health programs should account for the complex interplay of co-infecting pathogens.

Dr. Jamie Rothenburger is a veterinarian who practices pathology and a PhD student at the Ontario Veterinary College. Twitter: @JRothenburger

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