Students and Histoplasmosis in Acapulco
Students and Histoplasmosis in Acapulco
Abstracts & Commentary
Synopsis: You probably never thought about college students returning from their rites of spring with histoplasmosis—but it happened this year. In this context, our associate editor also reviews the recently published guidelines for the treatment of histoplasmosis, a potentially serious infectious disease, with several different clinical manifestations.
Sources: CDC. Outbreak of acute respiratory febrile illness among college students—Acapulco, Mexico, March 2001. MMWR Morb Mortal Wkly Rep. 2001;50(14):261; CDC. Public Health Dispatch. Update: Outbreak of acute febrile respiratory illness among college students—Alcapulco, Mexico, March 2001. MMWR Morb Mortal Wkly Rep. 2001;50:359-360; Wheat J, et al. Practice guidelines for the management of patients with Histoplasmosis. Clin Infect Dis. 2000;30:688-695.
Cdc recently reported an acute outbreak of febrile respiratory illness compatible with acute pulmonary histoplasmosis, occurring in college students returning from spring break holidays in Acapulco, Mexico. As of May 1, 44 colleges in 22 states reported 229 students who returned from Acapulco with an acute respiratory febrile illness defined as fever for at least 3 days and 1 or more of the following symptoms: cough, shortness of breath, chest pain, or headache. Initially, 21 students presented with fevers, dry cough, chest pain, and headache, and 2 students had patchy pulmonary infiltrates. At least 10 students had been hospitalized. Gomori methenamine silver stain of a transbronchial specimen suggested the presence of Histoplasma capsulatum in 1 student. Initially, specimens from 5 students returning with this syndrome in 3 separate states serologically tested positive for histoplasmosis using immunodiffusion and complement fixation tests. CDC first issued a travelers’ warning for Acapulco available on the web: http://www.cdc.gov/travel/other/res-mexico-apr2001.htm. Physicians should contact the CDC’s Mycotic Diseases Branch at (404) 639-1299. Since the first report in April, a cohort study has been performed among college students who stayed at 3 hotels in the area during the first 2 weeks of March and defined the relative risk of acquiring acute infection at these hotels. Analysis of 109 students indicated the risk ratio (RR) for this illness was 13.8 (P < .001) for those students (31) who had stayed at the Calinda Beach Hotel. The outbreak appears to be ongoing since a couple from California who stayed at the same hotel in early April appear to have also acquired documented histoplasmosis. Detailed cohort studies aimed at determining specific activities and exposures are being conducted among college students. The source(s) of the infections is not yet known, and may not be, until soil sample analysis for H capsulatum is also completed. Serological studies are also in progress using acute and convalescent phase serum specimens tested by complement fixations and immunodiffusion methods.
Comment by Michele Barry, MD, FAcp
Most cases of acute pulmonary histoplasmosis in immunocompetent persons are self-limited and will not require treatment. Prolonged cases, lasting more than 1 month, would require antifungal therapy. Wheat and colleagues review all the indications for antifungal treatment for pulmonary histoplasmosis and its complications in a recent practice guideline paper appearing in Clinical Infectious Diseases. Severity of illness depends on intensity of exposure acquired from the usual source of soil inhalation and the immunity of the host. Hematogenous dissemination from the lungs occurs in all infected individuals during the first 2 weeks of infection but is usually nonprogressive and leads to asymptomatic calcified granulomas in the liver and/or spleen.
Progressive dissemination occurs primarily in patients with immunosuppressive disorders or in patients at the extremes of age. Progressive pulmonary infection is also common in patients with underlying centrilobular emphysema. Chronic manifestations of histoplasmosis appear to result from unusual inflammatory or fibrotic responses to infection. Rheumatologic syndromes and pericarditis can occur within the first year of infection, and chronic granulomatous, fibrosing mediastinitis, or broncholithiasis occur later. A variety of treatment options exist, but the most important decision for the physician caring for a patient with histoplasmosis is whether to observe or treat. (See Table 1.)
Table 1: Indications for Antifungal Treatment in Patients with Histoplasmosis | ||
Treatment indicated | Treatment not indicated | |
Acute pulmonary histoplasmosis with hypoxemia | Acute self-limited syndromes | |
Acute pulmonary histoplasmosis for >1 month | Acute pulmonary histoplasmosis, mildly ill | |
Chronic pulmonary histoplasmosis | Rheumatologic | |
Esophageal compression and/or ulceration | Pericarditis | |
Granulomatous mediastinitis with obstruction | Histoplasmoma and/or invasion of tissue | |
Disseminated histoplasmosis | Broncholithiasis | |
Fibrosing mediastinitis* | ||
* Antifungal therapy has not been proven to be effective for this form of histoplasmosis but should be considered, especially in patients with elevated erythrocyte sedimentation rates or complement fixation titers > 1:32. | ||
Adapted from: Wheat J, et al. Practice guidelines for the management of patients with histoplasmosis. Clin Infect Dis. 2000;30:688-695. | ||
Acute Pulmonary Histoplasmosis: Treatment of Moderate Disease
Fever, chills, headache, myalgias, and pleuritic chest pain are seen in 85-100% of cases. Rales and pleural friction rubs may occur. Treatment is not indicated in the typical immunocompetent patient unless one shows lack of improvement at 1 month. Itraconazole, 200 mg daily, by mouth for 6-12 weeks would then be administered.
Severe Disease
If a patient becomes severely hypoxemic or requires ventilatory support, then amphotericin B 0.7 mg/kg/d, or an appropriately dosed lipid preparation of amphotericin for a patient with renal impairment should be administered initially. Corticosteroids might be considered as adjunctive therapy (60 mg/d) for 2 weeks because an inflammatory response is often a contributor to respiratory compromise. Itraconazole 200 mg twice daily is used to complete a 12-week course once the patient stabilizes clinically on amphotericin B. If amphotericin is used exclusively, a total course of up to 35 mg/kg over 2-4 months is recommended. (See Table 2.)
Table 2 Summary of Treatment Recommendations for Patients with Histoplasmosis |
||
Severe manifestation | Moderately severe or mild manifestation | |
Type of histoplasmosis | Treatment | Treatment |
Acute pulmonary | AmB with corticosteroidsa then Itr for 12 w | Symptoms < 4 w; none; persistent symptoms for > 4 w; Itr for 6-12 w |
Chronic pulmonary | AmBb then Itr for 12-24 mo | Itr for 12-24 mo |
Disseminated in non-AIDS | AmBb then Itr for 6-18 moc | Itr for 6-18 mo |
Disseminated in AIDS | AmBb then Itr for life | Itr for life |
Meningitis | AmB for 3 mo then Flu for 12 mo | Same as for severe because of poor outcome |
Granulomatous mediastinitis | AmB then Itr for 6-12 mo | Itr for 6-12 mo |
Fibrosing mediastinitis | Itr for 3 mod | Same as for severe |
Pericarditis | Corticosteroids or pericardial drainage | Nonsteroidal anti-inflammatory agents for 2-12 w |
Rheumatologic | Nonsteroidal anti-inflammatory
agents for 2-12 w |
Same as for severe |
a Effectiveness of corticosteroids is controversial | ||
b If amphotericin B is used for the entire course of treatment, 35 mg/kg should be given over 3-4 months | ||
c Therapy should continue until Histoplasma antigen concentrations are < 4 U in urine and serum | ||
d Therapy is controversial and probably ineffective except in cases of granulomatous mediastinitis that are misdiagnosed as fibrosing mediastinitis | ||
e If corticosteroids are administered, concurrent antifungal therapy is recommended. | ||
Adapted from: Wheat J, et al. Practice guidelines for the management of patients with histoplasmosis. Clin Infect Dis. 2000;30:688-695. | ||
Length of Therapy
For disseminated histoplasmosis occurring in non-AIDS patients therapy should continue until histoplasma antigen concentrations are < 4 units in urine and serum. AIDS patients will require chronic maintenance with itraconazole after the initial 12-week induction therapy period. Antigen concentrations should be monitored for life in both serum and urine, every 3-6 months in AIDS patients with a history of histoplasmosis.
Prophylaxis
Travel medicine providers should consider advising prophylaxis (itraconazole 200 mg once daily) for immunocompromised travelers with CD4 lymphocyte counts less than 150 who are going to regions experiencing high rates of histoplasmosis (> 5 cases 100 patient- years). Fluconazole is not an acceptable alternative to itraconazole for prophylaxis against histoplasmosis.
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