Coccidioidomycosis  

Background

Coccidioidomycosis is typically caused by inhalation of infectious arthrospores of the soil dwelling fungus, Coccidioides immitis. The disease was first reported in animals in 1940 and is endemic in the southwestern United States.

Endemic areas for C. immitis include California, Nevada, Utah, Arizona, New Mexico and Texas as well as Mexico, Central and South America. Humans and animals can be infected, especially when hot, dry conditions exist and favor inhalation of arthrospores spread by wind or physical disturbance of infected soil. Individuals travelling in infected areas are also at risk for contracting the disease, so travel history is important as weeks to even years can pass before clinical signs appear. Many animal infections are subclinical and depend on the competency of host cell-mediated immunity to remain in check. Cats appear more resistant to the clinical disease, whereas humans and dogs can develop severe disseminated disease, especially if immunocompromised (neoplasia, pregnancy, immune-mediated disease, viral infection, prolonged or severe stress). Burial of infected animals in endemic areas is ill-advised, because soil contamination can last many years. Infection cannot be spread directly between animals or from animals to humans.

Demographics of Infection

A review of 218 canine cases at University of Calif., Davis found 43 breeds and mixed breeds represented, predominantly young adult males of medium and large breeds (62% < 4 years, 63% males, and 78% medium to large size), and 76% were primarily outdoor dogs kept in backyards or for hunting and herding. Breeds stated to be at apparent increased risk include boxer, pointer, Australian shepherd, beagle, Doberman pinscher, and Scottish terrier.

Clinical Signs

Primary cutaneous disease is relatively uncommon and exhibits painless, firm, indurated nodules with central ulceration, occasional draining tracts, and regional lymphadenitis and lymphadenopathy. All cutaneous lesions should be assumed to result from disseminated disease unless proven otherwise. The classical acute, primary pulmonary disease (80% of cases) causes a severe productive cough from widespread lung involvement (nodules, consolidation) and tracheobronchial lymphadenopathy seen radiographically. Other systemic signs occur in 20% of cases and can include antibiotic non-responsive low-grade fever, depression, exercise intolerance, weakness, anorexia, and lameness with soft tissue swelling and bone pain. Bone is a common site for disseminated infection which can occur without pulmonary signs or lesions. It should be considered in greyhounds, along with their relatively high risk of long bone trauma and neoplasia, during workup for painful lameness (serology, location or exposure to endemic region, x-ray, bone biopsy). While early clinical signs are often self-limiting, some cases progress to systemic infection including CNS, GI, ocular, cardiac, liver, splenic, prostatic and renal involvement.

Hematologic and biochemical findings are variable and nonspecific. A definitive diagnosis is made by direct observation of C. immitis by cytology of tracheobronchial lavage, draining skin lesions, and lung, lymph node or tissue aspirates. Multiple site bone specimens should be taken as finding organisms can be difficult in some cases. Radiographs reveal varied changes with the pulmonary disease. The fungus grows readily in culture in 3-10 days. Serology yields a positive IgM precipitin test in 2-5 weeks with subsequent positive IgG complement fixation (CF) test in 8-10 weeks. High titers usually reflect disseminated disease. During recuperation CF titers can persist at low levels (1:4).

Systemic fungal chemotherapy is recommended for all forms except for the primary cutaneous disease, to prevent dissemination of infection. The azoles, ketoconazole (Nizoral®, 5-15 mg/kg PO q 12 hr) and itraconazole (Sporanox®, 5-10 mg/kg, PO q 12-24 hr), both given with food, are the drugs most widely used for dogs and cats. The former is less expensive but has more side effects. Fluconazole (Diflucan®, 2.5-5 mg/kg PO or IV q 24 hr) is also used but is very costly. Amphotericin B in liposome form (Abelcet®, 1 mg/kg IV QOD for up to 12 mg/kg) is used for serious disseminated disease and is less nephrotoxic. Nikkomycin and lufenuron are newer drugs under study. Treatment with azoles should continue for at least 2 months following resolution of clinical signs (a total of 6-12 months for disseminated disease). Relapses can occur. Azoles are mutagenic and cannot be used during pregnancy. The extremely high cost of treatment is a major deterrent. Asymptomatic dogs with positive CF titers do not need to be treated but should be monitored for signs of disease.

Coccidioidomycosis Serology

Test codes

Lead Poisoning in Pets

Despite widespread efforts to caution pet owners about the hazards of exposure to lead, accidental poisoning with this heavy metal still occurs.

Fortunately, rapid and reliable testing, along with well-defined therapies, are available to the veterinary practitioner when lead poisoning is suspected. Forty-two (13%) of 325 dog and cat whole blood samples submitted to a California regional toxicology laboratory for lead testing between 1990-1994 had detectable levels of lead. Most of these positive samples (33, 10% of the total) had significant exposure (> 10 ug/dl). Over half of the significant exposures (20%, or 6% overall) were at toxic levels (>30 ug/dl).

All species of animals, including caged birds, can be affected. Ingestion is the usual route of exposure, and young animals are especially at risk because of their efficient absorption from the gut. Sources of lead include figurines and toys, solder, plumbing supplies, shot, sinkers, improperly glazed bowls, lead-based paint such as from building remodeling or artist's paint, car batteries, tile and linoleum, and foil from wine bottle tops. Cats will lick leaded paint dust that has settled on their haircoats during remodeling.

Lead affects thiol- and zinc-enzymes, GABA-mediated neurotransmission, hemoglobin synthesis, and red blood cell membranes. The nervous, hematopoietic, and gastrointestinal systems are thereby involved. Lead poisoning in dogs may cause blindness, ataxia, circling, muscle spasms, hysteria, convulsions, mental slowness, abdominal pain, vomition, diarrhea or constipation, and anemia. Poisoned cats may have nonspecific signs of lethargy and anorexia. Horses can suffer from peripheral nerve demyelination leading to the "roarer" syndrome. Psittacine birds have an acute onset of vague signs including depression, weakness, anorexia, diarrhea, ataxia, head tilt, blindness, circling, and convulsions.

Diagnosis of lead poisoning is based on a history of exposure to lead, typical signs, anemia with inappropriate numbers of nRBC and/or basophilic stippling of red blood cells, radiographic evidence of lead in the gut (not always present), and analytical evidence of lead in blood or tissue. Whole blood drawn into lavender top tubes (LTT) containing EDTA or green top tubes containing heparin is the sample of choice to test for lead levels in live animals. The minimum blood sample volume is 100ul. At postmortem, ingesta, liver, and kidney (frozen, not fixed) are tested for lead. A blood lead concentration > 10 ug/dl suggests significant exposure, and > 30 ug/dl with appropriate signs indicates poisoning. Lead poisoning may be confused with rabies, distemper, hepatitis, and other heavy metal poisonings, and in cats, with other causes of unexplained anorexia and depression.

Treatment of lead poisoning begins with decontamination so that exposure to the source of lead is ended. Lead objects in the GI tract can be removed surgically. Otherwise, oral sodium or magnesium sulfate (0.5 mg/kg, in a 10% solution in water) can be used to remove residual lead, which must be done before using chelating agents. Ca EDTA (Versenate®, 25 mg/kg PO q 6 hr in 5% dextrose/water for 5 days) chelates lead and hastens secretion. The parenteral regimen must be followed by 2 to 4 days of rest before giving another round of therapy (if needed), to minimize renal damage. Severe cases may require chelation with BAL (dimercaprol) to remove lead from the brain before EDTA can be used. New agents, for example DMSA (dimercaptosuccinic acid), are being developed that will chelate lead with the efficacy of BAL and relative safety of EDTA.

Treatment of lead poisoning in pets should be accompanied by a discussion about decontamination of the premises. Urge owners to test other animals, and to seek medical advice regarding testing of children and other people, who may have been exposed to the toxic environment.

LAB TIPS

Platelet Size

Large platelets (megathrombocytes) are young and generally more active than normal sized platelets. Conversely, the presence of predominantly small platelets (microthrombocytes) in canine blood appears to be a specific indicator of immune-mediated thrombocytopenia (IMT). This conclusion is based on data from 68 thrombocytopenia cases (Northern, J. Jr. and Tvedten, H.W. JAVMA 200: 368-376, 1992). Small platelets (mean platelet volume < 5.4 fl) were found in 17 of the 31 IMT cases in this group, but only in 1 of the remaining 37 dogs.