Can We Put a Full Stop to Cat Scratch Disease?

Medicine

Photo: Wix

What is cat scratch disease (CSD)?

Despite its name, it is not a disease that cats suffer from. It is an infection that people catch from cats, caused by a bacterium called Bartonella henselae. Cats carry the bacteria in their blood, and most of them never show a single sign of illness. People, however, can get sick when an infected cat scratches or bites them hard enough to break the skin, or licks an open wound.

Around one to three weeks later, the lymph nodes closest to the scratch can become swollen and tender. Other symptoms include fevers, headaches, poor appetite and exhaustion. Children under 15 are the most likely to be diagnosed. Most cases clear up on their own, but in rare cases the infection can spread to the eyes, liver, brain or heart valves.

According to a study of Spanish hospitals, 781 people were admitted with cat scratch disease between 1997 and 2015, and those were only the most serious cases. Furthermore, many milder cases are likely never recorded at all, and up to one in three healthy cats may be carrying the bacteria without their owners knowing. It is a problem worth putting a full stop to.

The real culprit: fleas

Cats mainly pick up Bartonella henselae from fleas. A flea that feeds on an infected cat swallows the bacteria, which multiply inside it and come out in its droppings, known as flea dirt. This flea dirt can collect under a cat's claws, so when the cat scratches someone, it carries the bacteria straight into the wound. In other words, if we get rid of the fleas, we cut off the disease at its source. There is currently no vaccine against cat scratch disease for cats or people, so flea control is our main line of defence.

In order to eliminate these unwelcome fleas, one of the fastest options is nitenpyram, a systemic insecticide sold as a tablet under the brand name Capstar. Once a cat swallows it, nitenpyram enters the bloodstream, so any adult flea that bites the cat takes in the insecticide and dies. It starts killing fleas within 30 minutes and kills over 90% of them within six hours.

However, there is a catch. Nitenpyram only lasts about 24 hours, and it only kills adult fleas, not their eggs or larvae. Longer-lasting treatments exist, such as a spot-on solution that protects a cat for 12 weeks, but every option has to be given again and again, and it only takes a missed dose or two for the fleas to return. This is what first made me wonder: what if a cat's protection against fleas could be permanent?

Could CRISPR make it permanent?

CRISPR (clustered regularly interspaced short palindromic repeats) is a gene-editing tool that lets scientists change DNA with remarkable accuracy. It works in two parts: a tailor-made guide RNA, which leads it to the exact section of DNA to be edited, and an enzyme called Cas9, which cuts the DNA at that spot. The cell's natural DNA repair process then takes over, which can switch a gene off or, with the right template, insert a new one.

My first idea was to combine nitenpyram and CRISPR into a single injection, so that a cat would become permanently resistant to fleas and pass that resistance on to its kittens. As I researched it further, however, I found three problems.

Firstly, DNA cannot carry a chemical. Genes are instructions for making proteins, and nitenpyram is a man-made compound, not a protein, so there is no way to write it into a cat's DNA. Secondly, as far as I could find, no one has identified a gene that would make a cat flea-proof or immune to Bartonella, so even with CRISPR there is nothing obvious to edit. Thirdly, edits made by injecting an adult cat would not reach its kittens. Only changes to eggs, sperm or embryos are passed on, and editing embryos raises serious ethical questions. Despite its high accuracy, CRISPR can also make mistakes, cutting DNA in the wrong place, and in an embryo those mistakes could be passed on to every future generation.

That doesn't mean permanent protection is impossible. It may just mean I was trying to edit the wrong animal.

Edit the pest, not the pet

Instead of changing cats, scientists could one day change fleas. Researchers fighting malaria are already doing something similar with mosquitoes, using a CRISPR technique called a gene drive. Normally, each copy of a gene has a 50% chance of being passed from a parent to its offspring. A gene drive pushes that close to 100%, so an edit can spread through an entire population in just a few generations.

In 2018, scientists at Imperial College London used a gene drive to target doublesex, a gene that decides whether a mosquito develops as male or female. Females that inherited two copies of the edit could not bite or lay eggs, and within 7 to 11 generations, the caged populations of malaria-carrying mosquitoes collapsed completely.

Could the same approach work on fleas? In theory, a gene drive that stopped fleas from breeding could do what no tablet can and protect cats for good. But it comes with real risks. A gene drive released into the wild could affect entire ecosystems and would be very hard to undo, which is why even the Imperial team stressed that years of further testing would be needed before any mosquitoes were released outside the lab.

What we can do now

For now, the best way to prevent cat scratch disease is simple: keep cats free of fleas all year round. Owners should ask their vet which flea treatment is right for their cat, keep its claws trimmed, avoid rough play, and wash any scratch or bite straight away with soap and water. They should also never use dog flea products on a cat, as some contain permethrin, which is toxic to cats.

In the long run, more research and tests are absolutely necessary before gene editing could play any part in this. But the goal is worth chasing. If scientists could find a safe way to protect cats from fleas for good, they would stop cat scratch disease at its source, and both cats and human beings would benefit. That would be an enormous step for science, and one I hope our generation of scientists will take on.