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ORIGINAL RESEARCH |
From the Kern Medical Center, Bakersfield, California.
Address reprint requests to: John W. Caldwell, PharmD Kern Medical Center Department of Internal Medicine 1830 Flower Street Bakersfield, CA 93305 E-mail: caldwelj{at}kernmedctr.com
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Abstract |
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Methods: Thirty-two women who delivered live infants or aborted fetuses in 1993 and had confirmed diagnoses of coccidioidomycosis were included in the study. Medical records were evaluated retrospectively for clinical characteristics, laboratory results, and disease course.
Results: Dissemination occurred in three of 32 cases. The most common management was supportive and symptomatic care. At 1 year, 26 of 32 had recovered. There were no maternal deaths.
Conclusion: The common depiction of coccidioidomycosis in pregnancy has overstated morbidity and mortality likely because of reporting bias. Many women will have favorable outcomes without drug treatment, and the practice of abortions or early delivery in subjects with active infection should be rare.
Infection with the pathogenic fungus Coccidioides immitis in pregnancy can be serious. The effect of infection on mother and fetus can be compounded by difficult treatment issues. Previous literature and current authoritative sources present differing viewpoints on the natural history of coccidioidomycosis in pregnancy, leading to variance in treatment. Historical analysis suggests pregnant women experience dissemination 40–100 times more frequently than the general population.1 Mortality rates of 20–90% have been reported in disseminated cases besides untoward effects on fetuses.2–7 Those reports have resulted in widely read infectious disease publications advising consideration of abortion or early delivery if active infection is present, depending on stage of pregnancy.8
Another viewpoint suggests that higher dissemination and mortality rates in pregnancy are contrary to the experience of practitioners and academic physicians in endemic areas and further that maternal death is rare.9–11 Reports of increased maternal morbidity and mortality rates might be artifacts of reporting bias, which have led to an inaccurate portrayal of the natural history of coccidioidomycosis in pregnancy.
In the latter part of 1991, a coccidioidomycosis epidemic began in California’s central valley and continued through 1994.12 During that time there were 8435 reported cases in Kern County, exceeding expectations by sevenfold, which presented a unique opportunity to evaluate the incidence and severity of coccidioidomycosis in pregnancy. The intent of this study was to determine presentation, clinical course, and outcome of coccidioidomycosis in a large group of new cases regardless of disease severity.
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The case group was defined as subjects with positive serology, consistent clinical symptoms, and onset of illness between 3 months before conception and 3 months postpartum. The time frame was to include all subjects in whom pregnancy could have influenced disease course. Serology was considered positive with two or more immunoglobulin (Ig) M antibodies (as detected by immunodiffusion or enzyme-linked immunosorbent assay [ELISA]) or with a complement fixation titer greater than or equal to 1:4 during the disease course. Symptoms consistent with the development of acute disease included fever, chills, cough, sputum production, and pleurisy. A skin reaction to spherule-derived coccidioidin was considered positive if an area of induration greater than or equal to 5 x 5 mm appeared at 48 hours. Subjects were excluded if they were asymptomatic, had negative serology, were infected outside the time limits, or if their medical records could not be located.
Outcome was evaluated 1 year after onset of symptoms or at last physician visit. Recovery was defined as lack of symptoms and discontinuation of treatment in less than 1 year. Prolonged illness was defined as treatment for 1 year or longer.
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Results |
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. Cough, fever, and erythema nodosum were the most common findings at presentation. An initial serum complement fixation titer that reached diagnostic significance (at or above 1:4) was observed in 23 of 32 cases. All women had serum complement fixation titers greater than or equal to 1:4, or two or more positive IgM antibodies by immunodiffusion or ELISA during disease course. Skin tests were positive in 12 of 15 tested, and eosinophilia (absolute number over 350 cells/µL) was present in four of 17 women tested. Initial chest radiographic findings were available in 25 of 32 cases. Nine presented with infiltrates, two with adenopathy, and one with pleural effusion. Normal findings were observed in 13 women.
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Extent of disease and outcome are presented in Table 2. There were no deaths, and dissemination was present in three of 32 cases. Most women (23 of 32) recovered without treatment. In the nine women treated, five received amphotericin B during pregnancy, and four received azoles postpartum.
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Discussion |
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Incidence of dissemination in pregnancy has been reported in 30–100% of cases, exceeding the rate in the general population by 40 to 100 times.8 In a review of published and unpublished cases in 1991, 78 cases were evaluated. Dissemination occurred in 43 (55%) and death in 27 (35%) subjects (Pappagianis D. Coccidioidomycosis and pregnancy [abstract]. In: Galgiani JN, ed. Proceedings of the 35th Annual Coccidioidomycosis Study Group Meeting. Tucson, Arizona: Veterans Affairs Medical Center, 1991:4). Our most significant observations were the 9% incidence of dissemination and the absence of maternal death. The 32 symptomatic women represented every known case in Kern County during a year when there were eight times as many total cases as usually reported.
Although the 9% incidence of dissemination was lower than that in all previous reports, it still exceeded the rate in the general population and in females of reproductive age by threefold. We reported a 4.7% rate of dissemination in 536 cases from 1991, at the beginning of the California epidemic.13 Only 2.9% of nonpregnant women aged 15–45 years in our series were confirmed with dissemination, which supports the historical view of increased risk of serious disease during pregnancy. The small number of disseminated cases (three) limits drawing conclusions about diagnosis and trimester relationships emphasized in previous publications.
There were no maternal deaths in this study, which is consistent with previous reports of decreased mortality rates when amphotericin B was commonly used for significant pulmonary and disseminated disease.1 Previous conclusions of mortality ranging from 13–47% were found by combining all reported cases in the literature with additional referral cases (Pappagianis D. Proceedings of the 35th Annual Coccidioidomycosis Study Group Meeting. Tucson, Arizona: Veterans Affairs Medical Center, 1991:4). Based on our study, the favorable outcome of appropriately treated pregnant women does not support routine consideration of therapeutic abortion in women with active disease, as recommended in the literature.8
Erythema nodosum has been shown to be prognostic of a benign clinical course.14 We found erythema nodosum in 59%, which compares with an incidence of 26% in all women, obtained from our 1991 survey, and 50% reported in the white adult women in the 1940s.15 Only 3% of the group with erythema nodosum received treatment, indicating a more benign symptomatology.
As with other patients who have coccidioidomycosis, clinical factors such as ethnicity, immune competence, skin test reactivity, presence of erythema nodosum, complement fixation titer, degree of pulmonary involvement, and presence of cavitary disease should all be considered when treatment decisions are made. Except for preference of amphotericin B because of the teratogenic risks of azoles, recommendations for therapeutic treatment in pregnant women are similar to those in nonpregnant subjects and have been reviewed in the literature.16
The favorable outcome in most pregnant women with coccidioidomycosis suggests that the need for abortion or early delivery to protect the mother or infant is rare. Risk factors known to be associated with serious disease should dictate treatment accompanied by careful monitoring and expert consultation.
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Footnotes |
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Received January 8, 1999. Received in revised form June 30, 1999. Accepted July 15, 1999.
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2. Vaughn JE, Ramirez H. Coccidioidomycosis as a complication of pregnancy. Calif Med J 1951;74:121–5.
3. Harris RE. Coccidioidomycosis complicating pregnancy: Report of 3 cases and review of the literature. Obstet Gynecol 1966;28:401–5.
4. Smale LE, Waechter KG. Dissemination of coccidioidomycosis in pregnancy. Am J Obstet Gynecol 1970;107:356–61.[Medline]
5. Walker MPR, Brody CZ, Resnik R. Reactivation of coccidioidomycosis in pregnancy. Obstet Gynecol 1992;79:815–7.[Medline]
6. Bernstein DI, Tipton JR, Schott SF, Cherry JD. Coccidioidomycosis in a neonate; maternal-infant transmission. J Pediatr 1981;99:752–4.[Medline]
7. Spark RP. Does transplacental spread of coccidioidomycosis occur? Report of a neonatal fatality and review of the literature. Arch Pathol Lab Med 1981;105:347–50.[Medline]
8. Stevens DA. Coccidioides immitis. In: Mandell GL, Bennet JE, Dolin R, eds. Principles and practices of infectious diseases. 4th ed. New York: Churchill Livingston, 1995:2365–75.
9. Cantanzaro A. Pulmonary mycosis in pregnant women. Chest 1984;86 Suppl:14S–8S.
10. Wack EE, Ampel NM, Galgiani JN, Bronniman DA. Coccidioidomycosis during pregnancy. Chest 1988;94:376–9.
11. Barbee RA, Hicks MJ, Grosso D, Sandel C. The maternal immune response in coccidioidomycosis: Is pregnancy a risk factor for serious infection? Chest 1991;100:709–15.
12. Centers for Disease Control. Update: Coccidioidomycosis—California, 1991–1993. MMWR Morb Mortal Wkly Rep 1994;43: 421–3.[Medline]
13. Johnson RH, Caldwell JW, Welch G, Einstein HE. The great coccidioidomycosis epidemic: Clinical features. In: Einstein HE, Catanzaro A, eds. Coccidioidomycosis: Proceedings of the 5th International Conference; August 24–27, 1994; Stanford University, Palo Alto, California. Washington, DC: National Foundation for Infectious Diseases, 1996:77–87.
14. Arsura EL, Kilgore WB, Ratnayake SN. Erythema nodosum in pregnant patients with coccidioidomycosis. Clin Infect Dis 1998; 27:1201–3.[Medline]
15. Smith CE, Beard RR, Whiting MEG, Rosenberger MHG. Varieties of coccidioidal infection in relation to the epidemiology and control of the diseases. Am J Public Health 1946;36:1394–402.
16. Galgiani JN. Coccidioidomycosis. West J Med 1993;159:153–71.[Medline]
This article has been cited by other articles:
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  I. M. Spinello and R. H. Johnson A 19-year-old pregnant woman with a skin lesion and respiratory failure. Chest, August 1, 2006; 130(2): 611 - 615. [Full Text] [PDF]
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 R. A. Cox and D. M. Magee Coccidioidomycosis: Host Response and Vaccine Development Clin. Microbiol. Rev., October 1, 2004; 17(4): 804 - 839. [Abstract] [Full Text] [PDF]
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