Fatal maternal disseminated coccidioidomycosis in a nonendemic area

VanBergen, William S.; Fleury, Frederick J.; Cheatle, Esther L.

doi:10.1016/0002-9378(76)90075-2

Cited by 31 publications

(4 citation statements)

References 2 publications

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“…Until recently, the increased susceptibility associated with pregnancy was considered to be unequivocal (99,136,137,238,274). In areas of high endemicity, approximately 0.1% of pregnancies have been complicated by coccidioidomycosis, with a resulting mortality rate of 88% (291). In a review of 65 women who had coccidioidomycosis during pregnancy, VanBergen et al (291) reported that 37 (57%) developed disseminated disease and, of these, 29 (78%) died.…”

Section: Risk Factors For Severe Disseminated Coccidioidomycosismentioning

confidence: 99%

“…In areas of high endemicity, approximately 0.1% of pregnancies have been complicated by coccidioidomycosis, with a resulting mortality rate of 88% (291). In a review of 65 women who had coccidioidomycosis during pregnancy, VanBergen et al (291) reported that 37 (57%) developed disseminated disease and, of these, 29 (78%) died. The later the gestation stage, the more likely it is that dissemination will occur (217).…”

Section: Risk Factors For Severe Disseminated Coccidioidomycosismentioning

confidence: 99%

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Coccidioidomycosis: Host Response and Vaccine Development

2004

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Coccidioidomycosis is caused by the dimorphic fungi in the genus Coccidioides. These fungi live as mycelia in the soil of desert areas of the American Southwest, and when the infectious spores, the arthroconidia, are inhaled, they convert into the parasitic spherule/endospore phase. Most infections are mild, but these organisms are frank pathogens and can cause severe lethal disease in fully immunocompetent individuals. While there is increased risk of disseminated disease in certain racial groups and immunocompromised persons, the fact that there are hosts who contain the initial infection and exhibit long-term immunity to reinfection supports the hypothesis that a vaccine against these pathogens is feasible. Multiple studies have shown that protective immunity against primary disease is associated with T-helper 1 (Th-1)-associated immune responses. The single best vaccine in animal models, formalin-killed spherules (FKS), was tested in a human trial but was not found to be significantly protective. This result has prompted studies to better define immunodominant Coccidioides antigen with the thought that a subunit vaccine would be protective. These efforts have defined multiple candidates, but the single best individual immunogen is the protein termed antigen 2/proline-rich antigen (Ag2/PRA). Studies in multiple laboratories have shown that Ag2/PRA as both protein and genetic vaccines provides significant protection against mice challenged systemically with Coccidioides. Unfortunately, compared to the FKS vaccine, it is significantly less protective as measured by both assays of reduction in fungal CFU and assays of survival. The capacity of Ag2/PRA to induce only partial protection was emphasized when animals were challenged intranasally. Thus, there is a need to define new candidates to create a multivalent vaccine to increase the effectiveness of Ag2/PRA. Efforts of genomic screening using expression library immunization or bioinformatic approaches to identify new candidates have revealed at least two new protective proteins, expression library immunization antigen 1 (ELI-Ag1) and a β-1,3-glucanosyltransferase (GEL-1). In addition, previously discovered antigens such as Coccidioides-specific antigen (CSA) should be evaluated in assays of protection. While studies have yet to be completed with combinations of the current candidates, the hypothesis is that with increased numbers of candidates in a multivalent vaccine, there will be increased protection. As the genome sequences of the two Coccidioides strains which are under way are completed and annotated, the effort to find new candidates can increase to provide a complete genomic scan for immunodominant proteins. Thus, much progress has been made in the discovery of subunit vaccine candidates against Coccidioides and there are several candidates showing modest levels of protection, but for complete protection against pulmonary challenge we need to continue the search for additional candidates

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Section: Risk Factors For Severe Disseminated Coccidioidomycosismentioning

confidence: 99%

Section: Risk Factors For Severe Disseminated Coccidioidomycosismentioning

confidence: 99%

Coccidioidomycosis: Host Response and Vaccine Development

2004

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“…Because susceptibility to coccidioidal dissemination is related to gender and to the presence or absence of pregnancy (23,47,53,54), we conducted studies to determine the effect of selected sex hormones on C. immitis in vitro.…”

mentioning

confidence: 99%

Human sex hormones stimulate the growth and maturation of Coccidioides immitis

Drutz¹,

Huppert²,

Sun³

et al. 1981

Infect Immun

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Because men and pregnant women show increased susceptibility to extrapulmonary dissemination of coccidioidomycosis, studies were conducted to determine the direct effect of human sex hormones and related compounds on the growth and maturation of Coccidioides immitis in vitro. 17 beta-Estradiol, progesterone, and testosterone were highly stimulatory for the parasitic phase of C. immitis growth whereas cholesterol, ergosterol, and 17 alpha-estradiol (a physiologically inactive stereoisomer of 17 beta-estradiol) lacked such effects. Rates of spherule maturation and endospore release were accelerated, in a dose-dependent fashion, by concentrations of 17 beta-estradiol occurring in normal women, with the most striking effects seen at levels encountered in advanced pregnancy. A stimulatory effect of 17 beta-estradiol on the saprobic phase of fungal growth was also detected. The nonsteroidal "antiestrogens" tamoxifen and nafoxidine had either stimulatory or inhibitory effects, depending on fungal strain and experimental conditions. Diverse strains of Cryptococcus neoformans, Candida sp, and Petriellidium boydii were unaffected by hormones that had distinct effects on C. immitis. These studies suggest that direct stimulation of C. immitis by human sex hormones may help to account for sex- and pregnancy-related predisposition to dissemination of coccidioidomycosis.

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“…Even though IgG antibody against coccidioidal CF is found in cord blood, there have been very few case reports of C. immitis invading the placenta [ [13] , [14] , [15] ]. According to a literature search, this is the fourth clinical case of pregnancy-associated disseminated coccidioidomycosis that was first diagnosed by histopathologic examination of the placenta [ 3 , 13 , 16 ]. It is thought that the spherules lead to a granulomatous reaction, whereas the endospores lead to a neutrophil-predominant reaction [ [14] , [15] , [16] ].…”

Section: Discussionmentioning

confidence: 99%