Section 7: Management Strategies for Uncomplicated Early Infections

Once a diagnosis of coccidioidal infection is established, and a thorough evaluation for enhanced risk and evidence of complications has been accomplished, a rational management strategy can be formulated (illustrated as in the flow diagram). Patients who do not have risk factors, symptoms, or physical findings suggestive of progressive infection can be classified

as having early uncomplicated infections. In general, at least 90% of

patients will fall into this category and can be safely managed by primary care practitioners. The remainder may benefit from consultation with a specialist in infectious diseases, pulmonary diseases, neurology, or another discipline to aid in developing a treatment plan. Their management is beyond the scope of this syllabus. The following are some guidelines for managing patients with uncomplicated infections.

Health education and recommendations to the patient and family

Very commonly, establishing a diagnosis will be of great help to the patient because it clearly identifies the nature of the illness and allows the practitioner the opportunity to explain what may happen in the future. A general review of how patients contract Valley Fever, the typical symptoms, the need for therapy or the lack of need for therapy may be helpful to put the patient's experience in a more general and knowledgeable context. Patient information leaflets have been prepared to facilitate this process and are available from the Valley Fever Center for Excellence. Explaining that the illness usually improves slowly over a period of weeks to even months will be useful in allowing patients to align their expectations with the natural history of the illness. The patient can be advised that he or she cannot transmit the infection to others and therefore poses no risk to others.

Although the prognosis is generally favorable for most patients, it is important to explain to patients some of the infrequent but possible complications, both pulmonary and extrapulmonary. Worsening respiratory symptoms should prompt reevaluation, and new focal symptoms outside of the chest should be noted and, if they persist, be brought to medical attention. With this description, the need for follow-up as the infection resolves even though therapy is not begun becomes clearer to the patient, and this should improve compliance.

Frequency of follow-up health care visits

At the core of management of uncomplicated coccidioidal infections is continued follow-up. This is needed to confirm that the illness remains uncomplicated and that more specific interventions are unnecessary. In addition, residual pulmonary abnormalities may remain, which should be documented for future reference so that they need not be unnecessarily reevaluated. In rare instances, coccidioidal infections and lung neoplasms have co-existed and this should be considered during the follow-up period.

The interval between medical visits varies according to the severity of the symptoms and the course of infection up to the point of diagnosis. If symptoms are still worsening follow-up visits or telephone contact might be appropriate within days to a week later since continued worsening may prompt reevaluation and for instituting antifungal therapy. On the other hand, if there is clear evidence of improvement, then a return visit might be appropriate in two to four weeks. After the first two or three visits, the intervals between visits typically range from one to several months. By two years, an uncomplicated coccidioidal infection can be considered resolved.

Monitors of the course of infection

Several clinical and laboratory findings are helpful to assess the course of infection. Generally systemic signs of fever, night sweats and weight loss are the first to abate as a coccidioidal infection improves. Respiratory symptoms of chest pain, cough, and sputum production may be more protracted. Not infrequently fatigue and an inability to resume normal activities are some of the last symptoms to resolve. Since this is commonly a chronic process, patients may fail to see changes in these symptoms from day to day, and only when asked to compare their current state with one week or one month earlier do they become cognizant of their improved course.

Laboratory studies can also be helpful in providing objective evidence of improvement. Erythrocyte sedimentation rate, often elevated with early coccidioidal infections, is an inexpensive measure of systemic inflammation and can be used to monitor improvement. Typically this would not be measured any more frequently than weekly. Also, the CF or IDCF antibody concentration is expected to decrease as a coccidioidal infection resolves and it is important to demonstrate this. If these results do not normalize as expected, then concern should be raised that complications may be developing and possibly further diagnostic studies would be in order. Repeated serologic testing should seldom be any more frequent than every two weeks and usually ranges from one to several months between tests.

Chest radiographs should be repeated to demonstrate either resolution of all pulmonary abnormalities or to document what residual abnormalities persist. Early in the course of infection the interval may be as frequent as several days until symptoms or radiographic findings demonstrate abnormalities to be stable or improving. Subsequent chest radiographs should be obtained every several weeks to every several months.

Antifungal therapy

For early uncomplicated coccidioidal infections, most patients can be managed without antifungal therapy. There are currently three commercially available oral antifungal drugs available with activity for treating coccidioidal infections: ketoconazole (Nizoral™, Janssen Pharmaceutica, Inc.), fluconazole (Diflucan™, Pfizer Corporation), and itraconazole (Sporonox™, Janssen Pharmaceutica Inc.). Published reports have demonstrated activity of all of these agents in treatment of complicated coccidioidal infections. Length of treatment for such patients typically ranges from one year to life-time, depending upon the location of the infection and underlying risk factors involved. The cost of therapy is substantial. Drug costs alone range from $5,000 to $20,000 per year, depending upon the specific drug and the daily dose prescribed.

For the self-limited form of infections, there are no published clinical trials comparing any antifungal agent to placebo.

Consequently, it is not known whether early treatment hastens clinical improvement or prevents complications. Although these are reasonable objectives, there are no studies to demonstrate that they can be achieved with antifungal therapy.

With these considerations in mind, we recommend not prescribing antifungal therapy routinely for early coccidioidal infections. Most patients resolve their infections without

treatment, and because the cost of treatment is substantial, this seems the prudent approach to most patients. However, selected patients should be treated if their degree of morbidity is unusually high and the possible, although unproven, treatment may be beneficial. Such a decision should be made on a case by case basis and usually with pulmonary or infectious diseases specialist consultation.