Valley Fever

Valley Fever

How Dogs Get Valley Fever

Valley Fever is caused by a fungus that lives in the desert soil in the southwestern United States.
• Like people, dogs are very susceptible to Valley Fever. Dogs primarily contract Valley Fever in the low desert regions of Arizona, New Mexico and southwestern Texas and the central deserts of California. Dogs accompanying people traveling through these areas or wintering in these warm climates have about the same chance as their owners of being infected.
Dogs comprise the majority of Valley Fever cases in animals.
• However, other animals can get the disease as well. Cats, llamas, non-human primates, horses, zoo animals, and even wild animals have been reported with Valley Fever.
Approximately 6-10% of dogs living in Pima, Pinal, and Maricopa counties in Arizona will become sick with Valley Fever each year.
• The rate of illness in other Valley Fever endemic locations is not known, but it is lower most places than central and southern Arizona.
Not all dogs who breathe in spores become sick.
• About 70% of dogs who inhale Valley Fever spores control them quickly. These dogs are asymptomatic and are probably immune to the disease afterwards. This is very similar to what happens in people.

The life cycle of Coccidioides

As part of its life cycle, the fungus grows in the soil and dries into fragile strands of cells.
• The strands are very delicate, and when the soil is disturbed – by digging, walking, construction, high winds – the strands break apart into tiny individual spores called arthroconidia or arthrospores. Dogs and other animals mainly acquire Valley Fever by inhaling these fungal spores in the dust and air. The dog may inhale only a few spores or many hundreds.
Once inhaled, the spores grow into spherules which continue to enlarge until they burst, releasing hundreds of endospores.
• Each endospore can grow into a new spherule, spreading the infection in the lungs until the dog’s immune system surrounds and destroys it. The sickness Valley Fever occurs when the immune system does not kill the spherules and endospores quickly and they continue to spread in the lungs and sometimes throughout the animal’s body.

Prevention of Valley Fever in Dogs

Currently, there is no sure fire way to prevent Valley Fever in pets short of never residing in or traveling through the areas where the fungus grows. Valley Fever endemic areas are among the fastest growing regions in the country, which makes encounters of animals and people with the fungus a likely event.

Things you can do to reduce the likelihood of your dog’s exposure to the fungus:
• Avoid activities that generate dust, reduce digging behavior by dogs, prevent sniffing in rodent holes, and keep dogs indoors more than outdoors. Treating the soil is currently not practical as the fungus lives in spotty areas and can live up to 12 inches deep in the ground. Yard ground cover that reduces dust, however, is helpful: grass and deep gravel or other dust-controlling cover.

A vaccine is under development.
• It is possible a vaccine will be available in the future to prevent Valley Fever or make it only a very mild illness in dogs. Vaccination against Valley Fever would be very useful for animals traveling to places like southern Arizona and southern California as well as for those dogs that live in these places.

Symptoms

The most common early symptoms of primary pulmonary Valley Fever in dogs:
• coughing
• fever
• weight loss
• lack of appetite
• lack of energy

Some or all of these symptoms may be present as a result of infection in the lungs. As the infection progresses, dogs can develop pneumonia that is visible on x-rays.

Sometimes the coughing is caused by pressure of swollen lymph nodes near the heart pressing on the dog’s windpipe and irritating it.
• These dogs often have a dry, hacking or honking kind of cough and the swollen lymph nodes can be seen on x-rays.

When the infection spreads outside the lungs, it causes disseminated disease.
The most common symptom of disseminated disease in dogs is lameness; the fungus has a predilection for infecting bones of the legs in dogs. However, Valley Fever can occur in almost any bone or organ of dogs.
Signs of disseminated Valley Fever can include:
• lameness or swelling of limbs
• back or neck pain, with or without weakness/paralysis
• seizures and other manifestations of brain swelling
• soft abscess-like swelling under the skin
• swollen lymph nodes under the chin, in front of the shoulder blades, or behind the stifles
• non-healing skin wounds that ooze fluid
• eye inflammation with pain or cloudiness
• unexpected heart failure in a young dog
• swollen testicles

Sometimes a dog will not have any signs of a primary infection in the lungs, such as coughing, but will only develop symptoms of disseminated disease, e.g., lameness, seizures. Very few of the signs of Valley Fever are specific to this disease alone and your veterinarian will do tests and x-rays to determine that your dog’s illness is Valley Fever and to rule out other causes.
• Valley Fever in dog’s bone below the knee

What about open sores or draining lesions? Can these make me sick or spread the fungus to the environment?

The form of the organism in the fluid of draining lesions is not considered to be infectious to people or animals.
• If your animal is receiving antifungal medication, the number of organisms shed in the fluid is also likely to be very low.

Nevertheless, draining lesions are best handled in a way to minimize the fluid in your environment.
• Where possible, wounds can be bandaged. Bandages should be changed daily or every other day and discarded in outside waste containers to minimize risk of having spores grow on the bandage material and become a risk to humans and others in the house.
• If the lesion is on the side or back of a dog, a T-shirt can be put on the dog and it should be changed and washed daily or every other day. Cleaning impermeable surfaces with dilute (10%) bleach will kill organisms. Hands should be washed after handling the wounds or bandages.
• For immunocompromised persons, pregnant and postpartum women, or babies and very young children living in a household with a pet that has a draining lesion, it is recommended you consult your physician regarding this issue and follow his/her advice.

Diagnosis

For owners living outside of the endemic area, diagnosis of Valley Fever requires suspicion of the disease from the dog’s history, its symptoms, and the results of examinations and tests performed by your veterinarian.
• If your dog has recently visited an area where the fungus can be acquired, telling your veterinarian about your dog’s travel history can be very helpful in deriving the diagnosis.
• In addition to examining your dog, your veterinarian is very likely to order diagnostic tests to help identify the Valley Fever infection.

Common tests include:
• Valley Fever blood test (also called cocci test, cocci serology, or cocci titer)
• general blood tests and blood cell counts
• chest x-rays
• bone and joint x-rays
Sometimes tests are negative early in the infection, especially the Valley Fever blood test, and they may need to be repeated in 3-4 weeks to establish the diagnosis.
In difficult cases, the routine tests are not very helpful in the diagnosis. Your veterinarian may recommend other tests to find out what is making your dog sick.

These tests are often more definitive:
• Culture of fluid or tissue samples from your dog to isolate and identify the fungus; this is highly specific
• Biopsies or aspirates with microscopic examination of cell, fluid, or tissue samples to visualize fungal organisms and inflammation in your dog
• For paralysis or seizures, a CT or MRI scan of the brain or spinal cord

Does my dog need a Valley Fever test?

If your dog lives in a region where Valley Fever is typical,
• your dog could need a Valley Fever test for any illness that manifests the common clinical signs – coughing, fever, weight loss, etc. – or illnesses with vague signs that will not go away. In addition, your dog will need some serum chemistries and white blood cell counts and sometimes x-rays to aid in diagnosing the illness. A positive test in and of itself is often not enough to diagnose Valley Fever.

For dogs that do not live in regions with Valley Fever but have traveled through or spent time in one,
• a Valley Fever test may be indicated for undiagnosed, unresolving illnesses. If your dog becomes ill outside the typical locations for Valley Fever, it is important to tell your veterinarian of your dog’s travel history.

What is a Valley Fever test/titer and what does it mean?

A Valley Fever test, Cocci test, or Cocci titer checks the blood to see if your dog is making antibodies against the Valley Fever fungus. If the test is positive, it means your dog has been infected with the fungus.

If the Valley Fever test is positive, the laboratory then performs a titer.
• The titer measures how much antibody your dog is making against the fungus. A titer is obtained by doubling dilutions of the positive blood (1:4, 1:8, 1:16, 1:32 . . .) until the test becomes negative. The titer that is reported to your veterinarian is the last positive dilution. The laboratories typically stop the titer at 1:256 and report the result as >1:256 if the dog’s blood is still positive.

In broad terms, a higher titer is equated with more severe disease.
• However, some very sick animals have low titers, or even negative Valley Fever tests. For these dogs, other diagnostic tests are necessary for diagnosing the illness. X-rays, blood cell counts, biopsies, and microscopic examination of cellular specimens are a few of the tests your veterinarian may need to run.

Asymptomatic dogs (infected but not showing any illness)
• may also have low titers, such as 1:4 or 1:8, sometimes 1:16. The titer is helpful in diagnosing Valley Fever in sick dogs, but other tests are usually needed to confirm the diagnosis.

Titers usually reduce over time as the animal’s disease heals.
• Dogs that start with low titers (1:4 or less than 1:4) may undergo little change in the titer. Monitoring your dog’s symptoms and other tests, such as blood counts and x-rays, will be better determinants of improvement in cases with low titers.

Some dogs will remain Valley Fever positive with a low titer for life.
• Continued treatment and monitoring of these animals needs to be determined by your veterinarian on a case by case basis.

Treatment

In most cases, a dog ill enough from Valley Fever to be seen by a veterinarian will require treatment with antifungal medication.
• Courses of medication are usually extensive, averaging 6-12 months.
• Dogs with disseminated disease in bones, skin, or internal organs usually require longer courses of medication.
• Central nervous system (brain or spinal cord) involvement frequently requires lifetime treatment with medication to keep symptoms from recurring.
Oral antifungal medication in the form of twice daily pills or capsules is the usual treatment for Valley Fever.

There are three common medications used to treat Valley Fever in dogs:
• Fluconazole (Diflucan)
• Itraconazole (Sporanox)
• Ketoconazole (Nizoral)
These medications all target the same pathway in the fungus to inhibit its growth in the dog, but they differ in some of their chemical properties and in their metabolism.

Some side effects common to all three drugs

Stomach and intestinal upset
• Lack of appetite, nausea, vomiting, and diarrhea

Elevations in liver enzymes
• Ketoconazole and itraconazole are extensively metabolized by the liver and 10-20% of fluconazole is metabolized by the liver. An individual dog may have a bad liver reaction to any of these drugs, but most tolerate them well. Your veterinarian will monitor your dog’s liver enzymes.

Birth defects in fetuses
• These medications should only be used in pregnant dogs when the benefits to the mother outweigh the risk to the developing puppies.

Fluconazole

Currently, this is the most widely prescribed oral Valley Fever medication in use by veterinarians in southern Arizona.

Advantages:
• Excellent absorption from the GI tract, even in dogs that are not eating
• Generally easier on the liver
• Will cross into the brain and eye tissues – drug of choice for infection in these sites
• Available as a generic drug at significant cost savings over Diflucan
Drawbacks:
• This drug is cleared by the kidney and dose may need to be reduced in animals with compromised kidneys
• May cause thinning or dryness of the coat with dandruff, which seems most noticeable or most common in black dogs; these effects are reversed when drug is withdrawn
• Occasional reports of excessive drinking and urination, or leaking urine while asleep
• In 2013, the generic drug underwent a 5-fold increase in price due to reduction in manufacturers of the generic

Itraconazole

In laboratory studies, itraconazole is a more potent drug against Valley Fever than fluconazole but has some drawbacks compared to fluconazole in the clinical setting.
Advantages:
• Often effective in cases not getting well on fluconazole
• Can be administered once daily instead of twice daily to most patients, which may be easier on owners and pets
Drawbacks:
• Will generally cost more to use than fluconazole
• More likely to increase liver enzymes; metabolized by the liver
• Less absorbable from the GI tract than fluconazole, therefore it must be administered with a meal in the capsule form
• Development of drug-related skin reactions ranging from mild ulcerations to severe abscesses or sloughing of hair and extensive dermatitis; this appears to be partially dose dependent; lower doses are less likely to result in this reaction
Itraconazole is available as a US generic capsule that is approximately equivalent to Sporanox in its ability to be absorbed from the intestine. The capsular form of this drug is specially formulated on dextran beads to aid in solubility, and hence absorption. Make sure your itraconazole capsules have little beads inside them and not a powder. Itraconazole capsules should be administered with food.
Sporanox also comes in a liquid formulation. This is not available in a generic form at the time of this writing. Liquid Sporanox may be a good choice for cats or for small dogs. Unlike the capsules, liquid Sporanox is better absorbed on an empty stomach.

Ketoconazole

The first oral Valley Fever drug available and is still in use, almost exclusively as a generic drug.
Important characteristics:
• Requires an acidic environment for absorption from the GI tract, it is often administered with Vitamin C to aid in absorption
• Has a higher incidence of stomach and intestinal upset than fluconazole
• Is a good Valley Fever drug in cases where it is making the dog well
• Makes male dogs infertile while they are taking the medicine, this is also reversible when the medication is stopped
• Causes a usually reversible lightening of the coat color, particularly prominent in red and gold dogs, most dogs return to a normal color after the medication is stopped

Amphotericin B

Amphotericin B is an old but very effective antifungal medication that is mainly used for extremely sick dogs in today’s veterinary practices. This drug must be administered intravenously in the hospital and has the serious drawback of toxicity to the kidneys. Newer lipid-based formulations of amphotericin B (brand names: Abelcet, Ambisome) have a much lower likelihood of damaging the kidneys and are mainly used in dogs that are either very ill with Valley Fever or are not recovering on oral medication.

Other Drugs

More recently introduced to the market for treatment of fungal disease in humans:
• Voriconazole (Vfend)
• Posaconazole (Noxafil)
The role of these drugs in treating human Valley Fever is not yet clear. Voriconazole has absorption and treatment characteristics similar to fluconazole, but is more potent in laboratory studies. Posaconazole is a liquid drug that is more potent than itraconazole with similar chemical characteristics. It is easy to administer to smaller dogs and cats. Both drugs are more expensive than itraconazole and fluconazole, though voriconazole is now available as a generic drug at a cost savings over the brand name product. These drugs would mainly be used for cases that have failed fluconazole and itraconazole due to their increased potency.

Terbinafine

Added to one of the common Valley Fever medications, may improve the response to treatment for dogs that are not getting well on their medication. There are no actual studies of this drug in dogs, but in the laboratory it can kill Valley Fever fungus growing in culture, and dogs are able to absorb the drug with good blood levels. Observations suggest about half of dogs that are responding inadequately to a single drug will improve with the addition of terbinafine. Side effects are low but could include increases in liver enzymes and intestinal upset.

Supportive Treatments for Sick Dogs

Other treatments for Valley Fever are mainly directed at supportive care: making your dog feel better while the antifungal medication starts to heal the infection.

Cough suppressants
• Your veterinarian may prescribe medicine to relieve coughing, especially if it is one of the major symptoms.
Pain and fever relief
• Anti-inflammatories or pain medication prescribed by your veterinarian may greatly help your dog’s attitude and appetite during the severe stages of the disease.
Nutritional support
• While some dogs eat reasonably well with Valley Fever, others shun food entirely. These patients need extra nutritional care, such as hand-feeding highly palatable food (e.g. cooked meats), placement of a feeding tube, or medication to reduce nausea and vomiting or stimulate appetite.
Hospitalization
• Dogs that are too sick to eat and drink and are becoming dehydrated or are in severe respiratory distress may need 24-hour care, intravenous fluids, oxygen, or other medication that can only be given in the hospital environment.

What is the best treatment for Valley Fever?

Treatment choices vary by the individual veterinarian and patient. Reasons for choice of medication include practitioner’s experience with the drugs, costs, side effects, efficacy, severity of illness, and convenience to the owner. If one medication is unsuccessful, another will often be tried. For disease of the brain and spinal cord, fluconazole (Diflucan) is the drug of choice. Fluconazole also penetrates tissues of the eye and should be employed in ocular cases.

What is the proper dose of Valley Fever medications?

Your veterinarian is skilled in the diagnosis and treatment of your pet’s illness. Should you feel that your dog is not responding or may have side effects to the medicine, you should first discuss your concerns with your veterinarian. If the results are not satisfactory, you can seek a second opinion.

What are the side effects of oral Valley Fever drugs (ketoconazole, itraconazole, and fluconazole) in dogs?

All Valley Fever medications have the potential to cause side effects in dogs.

The side effects that are common to all of them are:
• Loss of appetite is the most common and may be severe in some dogs.
• Vomiting and/or diarrhea.
• Elevated liver enzymes – monitored with regular testing of your dog’s blood by your veterinarian.
• Birth defects in fetuses; therefore, medicine should be used only when benefits to mother outweigh risks to babies.

Less common or drug specific side effects include:
• Lightening of the coat color, especially in red or golden dogs. Effects reverse with discontinuation of the medication (with the exception of a few black dogs this author has heard about that have remained grey). (ketoconazole)
• Dry, thin coat and dry skin with dandruff. (fluconazole)
• Excessive drinking and urination, leaking urine in sleep. (fluconazole)
• Ulcerated or abscess-like lesions of the skin. (itraconazole) A reduction in dose may reduce this side effect, or the dog may have to discontinue the medication.
• Infertility in males (common with ketoconazole; possible with fluconazole; unknown with itraconazole). Reversible when drug is withdrawn.

What happened to the price of generic fluconazole & what can I do about it?

In 2013, most of the manufacturers of generic fluconazole stopped making it. There are only a few manufacturers left, which has driven the price up 5- to 10-fold, and has created a hardship for dog owners, especially of larger dogs. This is the result of manufacturers ‘charging what the public will bear’. (Read more about this). It is recommended that owners call different pharmacies to check for the best pricing of fluconazole.

Fluconazole can also be compounded, which generally costs less than generic medication, but compounding also increased in price in 2013. Compounded fluconazole generally works fine, but there may be more prescription-to-prescription variability in the drug than when buying generic. If your dog is not doing well on compounded fluconazole, it is worthwhile to try the generic and see if there is a difference. Online purchase may also be an option, but the research we have done shows little advantage to online pricing for fluconazole, at least for dog owners in Arizona.

Are there vitamins, nutritional supplements, or alternative therapies for dogs with Valley Fever?

Most ill dogs could receive a pet multivitamin supplement safely and possibly with benefit to overall well-being.
• Vitamin C is often prescribed to be administered with ketoconazole. This aids absorption of the drug by helping to acidify the stomach and may also “boost” the dog’s immune system. Use of the vitamin C should be checked with your veterinarian as high doses may cause gastrointestinal irritation.

Talk to your veterinarian about your dog’s overall nutrition status
• and the nutritional goals you need to meet while your pet is ill. The more ill your dog, the more important it is to discuss this issue with your vet.

Meet the nutritional needs of your dog with high quality, palatable food.
• Your dog may have to be hand fed for a period of time. Warming and moistening food are ways to make it more palatable. Foods may need to be rotated frequently while your dog’s appetite is poor to keep him interested and eating. There are also medications you can discuss with your veterinarian to try to stimulate appetite. Controlling fever and pain will also help the appetite of dogs. If the dog’s nutritional needs can’t be met with a highly palatable diet or hand feeding regimen and appetite stimulants, surgical placement of a feeding tube is an alternative, but seldom needs to be done.

Denamarin, a combination of a milk thistle extract (silymarin) and SAM-e, has antioxidant properties that help the liver cope with the “stress” of the Valley Fever drugs.
• If dogs are experiencing mildly elevated liver enzymes, Denamarin, Denosyl, or high quality health food store versions of milk thistle and SAM-e will often result in lowered enzymes at the next blood test. Check with your veterinarian for doses of the supplements. Denamarin and Denosyl are veterinary products adjusted for your dog’s body weight and these are recommended. Check with your veterinarian to buy these products and get advice on using them. If your clinic does not carry them, they are available online, but should be used under the instruction of your veterinarian.

Alternative therapies, such as herbs or acupuncture, have not been scientifically tested to treat Valley Fever.
• The majority of veterinarians to whom I have spoken use these therapies adjunctively with antifungal drugs to help support the dog’s overall health and to improve function of the immune system. If you wish to pursue alternative treatments, this author recommends you consult a veterinarian trained in holistic medicine. These professionals are your best source of help.

Prognosis / Outcome
Most dogs, with adequate antifungal therapy, do recover from this disease, especially with early diagnosis and intervention.

Dogs with uncomplicated (mild to moderate) infection only in the lungs
• have the best prognosis for recovery and usually respond the quickest to treatment. However, dogs can have extensive lung disease that is so severe and progressive that they require hospitalization, or surgery to remove diseased lung, or may die.

Dogs with disseminated infection
• As with lung infections, the majority of dogs with disseminated disease respond well to medication and lead normal lives, though they often require prolonged drug treatment (12-18 months). A small proportion of animals must take medication for life, and another small number, unfortunately, die of Valley Fever in spite of drug treatment. Dogs with disease in many locations in their bodies, dogs responding poorly to treatment, and dogs who have progressive disease in the face of medication, carry the most guarded prognoses.

Dogs with Valley Fever in the brain (seizures, etc)
• also carry a guarded prognosis. Among those that respond to medication (about 80%), most will remain well with fluconazole (Diflucan), but treatment may be required for life. These dogs will transiently need treatment with anti-seizure medication and steroids for brain swelling in addition to antifungal medication.

In animals with severe bone infections and the pain that goes with them

Pain medicine and anti-inflammatories can be prescribed by your veterinarian.
• Pain relief will often provide the comfort and support needed to allow the Valley Fever medication time to take effect. Treatment of high fevers with anti-inflammatories is helpful, since fever reduction can improve the appetite and energy level of the dogs, and simply improve the way they feel overall.

For dogs that are seriously ill, requiring hospitalization and supportive therapy, the prognosis can be grave.
• With aggressive treatment, possibly including intravenous antifungal medication, these patients may get well. Some dogs do not recover in spite of everyone’s best efforts, either due to the severity of illness at the time of diagnosis or because of long-standing, poorly responsive disease. Fortunately, they represent a minority of dogs with Valley Fever.

Statistics regarding how many dogs recover compared to those which do not are not available, but in general, more than 90% of dogs respond and recover.

Stopping Treatment

Treatment of Valley Fever in your dog is monitored by rechecks with your veterinarian.
• Your veterinarian will examine your dog to look for improvement as well as performing blood tests and possibly x-rays to monitor progress and make sure the medication is not harming your dog. If your dog is very ill, rechecks may be frequent at first. As the disease stabilizes and recovery becomes apparent, your veterinarian will probably only need to evaluate your dog every 2-4 months.

Medication
• It is very important to continue medicating your dog as directed until the veterinarian confirms that the blood tests are improved and tells you to stop medication. If you stop treating too soon, symptoms may recur. If symptoms recur after your dog is taken off medication, your veterinarian will probably recommend resuming treatment and may suggest the dog remain on medication for life.

Can Valley Fever relapse and can dogs be reinfected?

Valley Fever is well known to relapse in both humans and dogs.
• In particular, cases of disseminated infection have a 30-50% rate of relapse in humans, no matter how well the initial infection was treated. It is not known how many canine cases of Valley Fever relapse, but relapses are not uncommon and the rate may be similar to people.

In the case of a relapse, a return to medication is usually enough to make symptoms subside,
• but the dog may require several additional months of treatment. Dogs that experience more than one relapse or get very sick with the relapse should probably have lifetime treatment with medication considered.

Reinfections
• a brand new infection from spores in the environment – in humans are documented only rarely. It is not known at this time whether dogs are susceptible to reinfection or whether recurring illness is always due to the original infection.

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