Valley Fever Information

A pharmacognosy approach to conventional drug therapy for reducing serologic titers in canine subjects diagnosed with the fungal disease, coccidioidomycosis.

Randall Thomason, M.S. Nutritional biochemistry            
December 10, 2007

The principal investigator is the former director of research & development for Pet Health Pharmacy of Youngtown, Arizona and an expert in drug and nutraceutical design for humans and animals.

Coccidioidomycosis is a fungal disease that specifically impacts humans and animals in the southwest. Commonly referred to as “Valley Fever” it is a perpetuating disease that may or may not respond to a limited variety of antifungal medications that yield varying degrees of reliability and success. Because of the opportunistic nature of the “cocci” organism it appears to have its greatest success in hosts whose immune defense has been compromised. As an alternative to standard antifungal compounds a holistic formula has been developed that offers not only fungistatic activity against the organism but the potential to fortify the immune system in a selectively toxic fashion that minimizes side effects often seen with accepted medications. In addition this design is structured to work outside of the cocci and fungal arena to address a variety of immune deficient disease processes such as cancer, arthritis, diabetes and a host of metabolic issues. Although the purpose of this study is to observe the effects of the nutritional formula on 10 canine subjects, research has shown that humans have the same susceptibility and a proposed follow-up would be the application of findings into a similar human study.

SIGNIFICANCE

Coccidioides immitis and the lesser seen coccidioides posadasii are soil-borne fungal spores found in the upper layer of soil in endemic regions of the Western Hemisphere including the semiarid geography of southern Arizona, Texas, New Mexico, and much of central and southern California. Endemic areas are also prevalent in semiarid areas of Mexico, Central and South America.1,2,3 Often disturbed by harvesting, dust storms, construction and rainfall, the spores then become airborne and can be easily inhaled by animal or human hosts.  Once inhaled, these saprophytic organisms form large spherules that eventually rupture and release hundreds of endospores into surrounding tissue, blood and/or lymphatic pathways.  If not attacked by the host’s immune system, each endospore will form an entirely new spherule to eventually rupture and release more endospores.  Herein is the complexity of the disease. Depending on the immunological status of the host, the fungus is either attacked or it goes on to propagate.4,5,6,7

Thus, it appears the desert might be waging its own war against urban sprawl and the population growth associated with it through a rapid increase in cases of coccidioidomycosis, or “Valley Fever” (VF) as it is known. To illuminate the scope of the coccidioides proliferation in humans, in Arizona between 1996 and 2006 reported cases skyrocketed from 2 % to 20% of total cases (655 to 5535.)8

Canines have similar susceptibility as that of humans with subclinical infections, pulmonary and disseminated disease.9 As with humans exposure frequently resolves on its own with approximately 70% of canines that inhale cocci spores remaining asymptomatic. Yet the disease impacts the remainder in degrees from mild to fatal.10 Dissemination, allows the fungus its own identity in each infected host11. Though not contagious, the fungus typically begins in the lungs as a respiratory infection. From there, skeletal, lymphatic, hepatic, splenic, neurologic and (less frequently) ocular and cardio regions are all susceptible targets.3,11,12

A recent study of canines indicated that titers for asymptomatic or healthy and subclinical dogs ranged from 1:2 to 1:16. The remainder of sick or clinically infected dogs had titers of < 1:2 to 1:32. Titers overlapped significantly among healthy and sick dogs.13 Localized versus systemic or disseminated disease generally occurs at serological titers of 1:16 to 1:32 or greater.14  Risk of infection in young dogs rises until later stages of adolescence when immunity to the fungus is thought to be a result of strengthened immunological defense.4,5

Medication regimens for both humans and canines vary greatly depending on individual response. The “azoles” (fluconazole, itraconazole and ketoconazole) are considered less toxic however they are fungistatic and, therefore, relapses are common and success rates can be as low as 50%. In severe cases amphotericin B is typically used.3,15,16,17,18 Adverse side effects can also be a drawback. In humans some of these side effects consist of hepatotoxicity, diarrhea, nausea, vomiting, fatigue, impotence, constipation, adrenal insufficiency and menstrual irregularities.19 While canines tend to react with hepatotoxicity, diarrhea, vomiting, anorexia, lightening of the haircoat, depression and adrenal insufficiencies.20

Dogs raised from birth in Pima or Maricopa County have a 28% chance of being infected from the fungus by two years of age13. As part of a routine physical exam the PI ordered titers for both of his golden retrievers that were born in each of these counties. Not only did both dogs test positive, but the 2-year-old female had a titer of 1:32 and possible dissemination to the bone yet clinically showed no signs of the disease. At the same time an acquaintance disclosed that her golden retriever had just contracted VF with the same 1:32 titer and was very sick. According to the local golden retriever rescue 20% of the dogs rescued have VF21. But sporting breeds represent the tip of the iceberg. For instance greyhounds, part of the hound group, are another purebred that seem particularly susceptible perhaps due to their normally low white blood cell counts and the connection to natural immunity15.

According to the National Pet Owner’s survey for 2007-2008 there are 44.8 million dogs in the US and people do not seem to be sparing any expense with their animal friends spending 9.3 billion on supplements and OTC meds22. Maricopa County has 250,000 licensed dogs which are believed to be just a fraction of total dogs23. There are probably millions of dogs in the southwest with potential exposure that could benefit from natural support.

In addition, there are an estimated 150,000 new VF infections in humans contracted annually in the southwest24. Arizona’s rich retirement population seems to be disportionately targeted as age of 65 or greater has a direct correlation with infection.25 Maricopa, Pima and Pinal county account for approximately 79% of Arizona’s population and 93% of all VF cases statewide.25

Humans and animals possess very specific immunological blueprints that remain unique to their chemistry and physiology.  Science and medicine have shown repeatedly that pathogenic invasions can occur opportunistically in compromised immunological environments.26 The cocci organism behaves as the ultimate opportunist, disrupting weakened immune systems in humans and animals, possibly impacted by illness, genetics, lifestyle, environment and diet (fast foods in humans and processed pet food in animals are two prevalent causes of malabsorption and malnutrition) and ultimately immune dysfunction.27

REFERENCES

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  2. Galgiani JN, Ampel NM, Catanzaro A, Johnson RH, Stevens DA, et al. (2000) Practice guidelines for the treatment of coccidioidomycosis. Clin Infect Dis 30:658-661
  3. Hector RF, Laniado-Laborin R (2005) Coccidioidomycosis-a fungal disease of the Americas. PLoS med 291):e2.
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  8. Arizona Department of Health Services; Bureau of epidemiology and disease control services; Office of infectious disease services [document on the internet].[cited 2007 Dec 06] Number of reported cases of notifiable diseases by year for Arizona, 1996-2006. Available from http://www.azdhs.gov/phs/oids/pdf/cases1996-2006.pdf
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    coccidioidomycosis. A randomized, double-blind trial. Mycoses study group. Ann Intern Med. 2000; 133(9): 676 - 686.
  17. Martino, 2004:Martino R Efficacy, safety and cost-effectiveness of amphotericin B lipid complex  (ABLC): a review of the literature. Curr Med Res Opin. 2004; 20(4): 485 - 504.
  18. Greene RT. Coccidioidomycosis. In:Greene CE, ed. Infectious Diseases of the Dog and Cat, 2nd ed. Philadelphia:WB Saunders;1998. p391-98,801-04.
  19. Deglin JH, Vallerrand AH. Antifungals. IN:Haitsh B. Allen R, editors. Davis’s Drug Guide for Nurses. 8th ed. Philadelphia: FA Davis Compmany;2003.C24,406,545,547.
  20. Allen DG. Pringle JH, Smith DA, Pasloske K. Description of drug’s for small animals. IN:Swan K. Ramsey L, Callaghan P, editors. Handbook of Veterinary Drugs. 2nd ed. Philadelphia: Lippincott-Raven;1998.182,213-14,219.
  21. Orwig D. Barking up the right tree. Golden Tales (Rescue a Golden of Arizona). 2007 Nov;IX(4):6.
  22. American Pet Products Manufacturers Association. Industry statistics & trends. 2007-2008 National Pet Owners Survey [cited 2007 Dec 9] [homepage available on the internet] http://www.appma.org/press_industrytrends.asp
  23. Haller S. The Arizona Republic. Chihuahuas – they are not. (09 Sept 2007) [cited 2007 Dec 8][article on the internet] available at http://www.azcentral.com/families/articles/09pets0909.html
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  25. Center for Disease Control. Coccidioidomycosis-Arizona, 1990-1995. MMWR 45(49);1069-1073. [1996 Dec. 13][document on the internet] Available at http://epo-xdv-www.epo.cdc.gov/wonder/prevguid/m0044697/M0044697.asp
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  27. Valleyfever.org [homepage on the internet].[cited 2007 Nov 26] Valley fever alternative medicine. Available from http://www.valleyfever.org/valley-fever_org_natural_therapies.html