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2.  Safety and Tolerability of Voriconazole in Patients with Baseline Renal Insufficiency and Candidemia 
Acutely ill patients with candidemia frequently suffer from renal insufficiency. Voriconazole's intravenous formulation with sulfobutylether beta-cyclodextrin (SBECD) is restricted in patients with renal insufficiency. We evaluated the use of intravenous voriconazole formulated with SBECD in candidemic patients with renal insufficiency and compared treatment outcome and safety to those who received a short course of amphotericin B deoxycholate followed by fluconazole. We reviewed data on treatment outcome, survival, safety, and tolerability from the subset of patients with moderate (creatinine clearance [CrCl], 30 to 50 ml/min) or severe (CrCl, <30 ml/min) renal insufficiency enrolled in a trial of voriconazole compared to amphotericin B deoxycholate followed by fluconazole for treatment of candidemia in 370 patients. Fifty-eight patients with renal impairment were identified: 41 patients on voriconazole and 17 on amphotericin B/fluconazole. The median duration of treatment was 14 days for voriconazole (median, 7 days intravenous) and 11 days for amphotericin B/fluconazole, 3 days of which were for amphotericin B. Despite the short duration of exposure, worsening of renal function or newly emerged renal adverse events were reported in 53% of amphotericin B-treated patients compared to 39% of voriconazole-treated patients. During treatment, median serum creatinine decreased in the voriconazole arm, whereas creatinine increased in the amphotericin B/fluconazole arm, before return to baseline at week 3. All-cause mortality at 14 weeks was 49% in the voriconazole arm compared to 65% in the amphotericin B/fluconazole arm. Intravenous voriconazole formulated with SBECD was effective in patients with moderate or severe renal insufficiency and candidemia and was associated with less acute renal toxicity than amphotericin B/fluconazole.
doi:10.1128/AAC.05841-11
PMCID: PMC3370805  PMID: 22450974
3.  Chronic vulvovaginal candidiasis: characteristics of women with Candida albicans, C glabrata and no candida. 
Genitourinary Medicine  1995;71(5):304-307.
INTRODUCTION--Although as many as 5% of all women complain of chronic vulvovaginitis, little is known about these women. They may often be misdiagnosed and the role of vaginal yeast culture in diagnosing vulvovaginal candidiasis (VVC) among them has not been clearly defined. METHODS--To address these deficiencies, we tabulated initial diagnoses among new patients and conducted a medical record-based, unmatched case-control study among women reporting a history of chronic vulvovaginitis (four or more episodes in the past year) at a vulvovaginitis specialty clinic. Clinical presentation and medical history were compared for women who had a positive vaginal yeast culture for either Candida albicans or C glabrata, or who had a negative culture. RESULTS--One-third of the women had no apparent vulvovaginal disease at their initial visit. All women reported similar symptoms, except for an increased prevalence of painful sexual intercourse in women with C albicans (chi 2 p = 0.014 versus women with C glabrata and p < 0.001 versus women with no candida). Women with C glabrata were more likely to be non-white (chi 2 p = 0.071 compared with women with C albicans) and to report an underlying medical condition (chi 2 p < or = 0.001 versus both women with C albicans and women with no candida). Physical examination was normal only in women with no candida. C albicans cases were more likely to have positive potassium hydroxide microscopy (chi 2 p = 0.016) and a pH < or = 4.5 (chi 2 p = 0.011) than were C glabrata cases. CONCLUSIONS--These results suggest that reliance on symptoms and signs alone will result in significant misdiagnosis of chronic vulvovaginitis. Among women with VVC, subtle differences in clinical presentation do not reliably distinguish women with C albicans from those with C glabrata. Our study also indicates that vaginal yeast cultures, while not necessary for every patient, are valuable in confirming negative diagnoses, detecting microscopy false-negatives, and identifying non-C albicans isolates.
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PMCID: PMC1195546  PMID: 7490047
4.  Identification of Candida species by randomly amplified polymorphic DNA fingerprinting of colony lysates. 
Journal of Clinical Microbiology  1997;35(8):2031-2039.
We have characterized a method that produces simple yet diagnostic fingerprints that are unique to isolates of Candida species. DNA from individual colonies can be amplified from crude single-colony lysates. Randomly amplified polymorphic DNA (RAPD) fingerprints generated from a single primer correctly identified the species of most (>98%) of the isolates identified with CHROMagar Candida plates as non-Candida albicans Candida species. RAPD fingerprints were much more informative than the plates, since they distinguished between all tested species and required less time. Most (91%) of these identifications agreed with those assigned by API 20C tests. In almost every incident of species identity mismatch, electrophoretic karyotyping showed that the RAPD fingerprint was correct. This underscores the improved objectivity and reliability of this method over those of conventional diagnostic tools. The identities of approximately 30% of C. albicans isolates identified in clinical laboratories by positive germ tube tests are not verified by either testing on CHROMagar Candida plates or RAPD fingerprinting. Data suggest that clinical isolates conventionally identified as C. albicans in clinical settings are heterogeneous, consisting of both misidentified and atypical yeasts. RAPD fingerprints obtained from primary culture plate colonies allows for rapid, highly accurate determinations of Candida species, hence permitting earlier selection of appropriate antifungal agents in the clinical setting.
PMCID: PMC229897  PMID: 9230376
5.  Fluconazole Susceptibility of Vaginal Isolates Obtained from Women with Complicated Candida Vaginitis: Clinical Implications 
Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 μg/ml) and 14 (3.6%) were resistant (MICs, ≥64 μg/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 μg/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates (n = 250) for which MICs were ≤1 μg/ml were compared with isolates (n = 30) for which MICs were >1 μg/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 μg/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.
doi:10.1128/AAC.47.1.34-38.2003
PMCID: PMC148960  PMID: 12499165
6.  Epidemiology of vulvar vestibulitis syndrome: an exploratory case-control study 
Sexually Transmitted Infections  1999;75(5):320-326.
BACKGROUND: Vulvar vestibulitis syndrome (VVS) is a chronic, persistent syndrome characterised by vestibular pain, tenderness, and erythema. The aetiology of VVS is unknown and few of the hypothesised risk factors have been tested in controlled studies. METHODS: Using a matched case-control study design, medical, sexual, health behaviour, and diet history of 28 women with VVS were compared with 50 friend controls without VVS to identify possible causal factors. RESULTS: Cases were more likely than controls to report every vaginal and urinary symptom at the time of interview measured, particularly vaginal soreness or pain (60.7%) and pain during intercourse (64.3%). There were no significant differences between cases and controls with respect to sexual behaviour. Cases were more likely than controls to report self reported history of physician diagnosed bacterial vaginosis (OR = 22.2, 95% CI = 2.8, 177.2, p value = 0.0001), vaginal yeast infections (OR = 4.9, 95% CI = 1.4, 18.0, p value = 0.01), and human papillomavirus (OR = 7.1, 95% CI = 0.6, 81.2, p value = 0.08). There were no differences between cases and controls with respect to dietary intake of oxalate. Cases were more likely than controls to report poor health status (OR = 5.7, 95% CI = 1.1, 28.7, p value = 0.02) and history of depression for 2 weeks or more during the past year (OR = 4.4, 95% CI = 1.6, 12.3, p value = 0.002). CONCLUSION: Self reported history of bacterial vaginosis, yeast infections, and human papillomavirus were strongly associated with VVS. An infectious origin for VVS should be pursued in larger controlled studies, using questionnaire and laboratory measures. 



PMCID: PMC1758242  PMID: 10616356
7.  Ketoconazole in the prevention of experimental candidal vaginitis. 
The prophylactic and therapeutic activities of ketoconazole were evaluated in rats inoculated intravaginally with Candida albicans. Daily doses of 2.5 mg/kg initiated 48 h before challenge and continued for 48 h thereafter protected 80% of the rats against infection. A similar result in rats with established infection was attained with daily doses of 5.0 mg/kg.
PMCID: PMC185491  PMID: 6324671
8.  Ulcerative colitis in the South African Bantu 
Gut  1970;11(9):760-763.
Two cases of ulcerative colitis in the Bantu are reported. One patient presented with fulminant acute colitis with toxic dilatation of the colon and massive rectal haemorrhage, the second with chronic, continuous diarrhoea for over twenty years, culminating ultimately with carcinoma of the colon.
The aetiology of ulcerative colitis is discussed, together with the problems of specific diagnosis encountered in a population with a high incidence of parasitic infestation and infective diarrhoea.
It is considered that the sparseness of reports and apparent rarity of this disease in the Bantu may reflect a failure of detection rather than a true infrequent occurrence. The natural incidence of the disease may be on the increase.
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PMCID: PMC1553115  PMID: 5312108
9.  In vitro activity of a new pneumocandin antifungal, L-743,872, against azole-susceptible and -resistant Candida species. 
The in vitro activity of a new pneumocandin, L-743,872, was evaluated with 108 strains of Candida and compared with the activities of various antifungals. L-743,872 demonstrated the best activity against azole-susceptible and -resistant strains of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. kefyr and less activity against C. krusei, C. lusitaniae, and C. guilliermondii.
PMCID: PMC163972  PMID: 9210698
10.  Efficacy of D0870 treatment of experimental Candida vaginitis. 
In this study, oral administration of the triazole D0870 was compared to oral administration of fluconazole in the treatment of experimental vaginal candidiasis. With an estrogen-dependent murine model of Candida albicans vaginal infection, the effects of D0870 on several isolates, including fluconazole-susceptible and -resistant isolates, were tested. D0870, at doses of 0.5 and 2.5 mg/kg of body weight given once over the course of a 10-day infection, was effective in eradicating vaginitis caused by fluconazole-susceptible laboratory and clinical isolates, respectively. In contrast, a stricter treatment regimen (every 24 to 48 h) with 10 and 25 mg of fluconazole per kg was required to achieve similar reductions in vaginal fungal titers induced by the same isolates. Whereas fluconazole was consistently ineffective in infections induced by fluconazole-resistant isolates, as predicted by in vitro susceptibility tests, D0870 was effective, although a daily regimen of 25 mg/kg was required. Additional studies showed that despite the in vitro activity of D0870 against two clinical Candida glabrata isolates, neither D0870 nor fluconazole was effective at daily doses as high as 100 and 125 mg/kg, respectively. Taken together, although D0870 failed to show efficacy against experimental C. glabrata vaginitis, D0870 was superior to fluconazole in the treatment of experimental C. albicans vaginitis caused by isolates that were either susceptible or resistant to fluconazole.
PMCID: PMC163939  PMID: 9210665
11.  Vaginal microbiology of women with acute recurrent vulvovaginal candidiasis. 
Journal of Clinical Microbiology  1996;34(10):2497-2499.
Alterations in the autochthonous vaginal microflora can predispose women to recurring attacks of Candida vaginitis. Quantitative aerobic and anaerobic cultures were obtained from 24 premenopausal women with acute recurrent vulvovaginal candidiasis and from 21 healthy asymptomatic premenopausal women. Lactobacillus species constituted the predominant flora in both groups, with a mean log10 CFU/ml of 8.7, a total isolation rate of 96%, and a mean of 1.6 Lactobacillus species isolated per patient compared with a mean log10 CFU/ml of 8.9, a total isolation rate of 90%, and a mean of 1.2 Lactobacillus species isolated per patient in the vaginitis and control groups, respectively. The results of this small study failed to provide evidence of an altered or abnormal vaginal bacterial flora in women with non-antibiotic-induced recurrent vulvovaginal candidiasis suffering from acute Candida vaginitis.
PMCID: PMC229302  PMID: 8880507
12.  Immunopathogenesis of recurrent vulvovaginal candidiasis. 
Clinical Microbiology Reviews  1996;9(3):335-348.
Recurrent vulvovaginal candidiasis (RVVC) is a prevalent opportunistic mucosal infection, caused predominantly by Candida albicans, which affects a significant number of otherwise healthy women of childbearing age. Since there are no known exogenous predisposing factors to explain the incidence of symptomatic vaginitis in most women with idiopathic RVVC, it has been postulated that these particular women suffer from an immunological abnormality that prediposes them to RVVC. Because of the increased incidence of mucosal candidiasis in individuals with depressed cell-mediated immunity (CMI), defects in CMI are viewed as a possible explanation for RVVC. In this review, we attempt to place into perspective the accumulated information regarding the immunopathogenesis of RVVC, as well as to provide new immunological perspectives and hypotheses regarding potential immunological deficiencies that may predispose to RVVC and potentially other mucosal infections by the same organism. The results of both clinical studies and studies in an animal model of experimental vaginitis suggest that systemic CMI may not be the predominant host defense mechanism against C. albicans vaginal infections. Rather, locally acquired mucosal immunity, distinct from that in the peripheral circulation, is now under consideration as an important host defense at the vaginal mucosa, as well as the notion that changes in local CMI mechanism(s) may predispose to RVVC.
PMCID: PMC172897  PMID: 8809464
13.  In vitro activity of a new pneumocandin antifungal agent, L-733,560 against azole-susceptible and -resistant Candida and Torulopsis species. 
Antimicrobial Agents and Chemotherapy  1995;39(12):2689-2691.
The activity of a new water-soluble pneumocandin, L-733,560, was evaluated with 107 pathogenic strains of Candida and Torulopsis, which included 23 strains with known multi-azole resistance patterns. In vitro evaluation of L-733,560 activity was performed by a broth microdilution method, and the activity was compared with the activities of amphotericin B, fluconazole, ketoconazole, itraconazole, and flucytosine. The mean MICs of L-733,560 were 0.15 microgram/ml for C. lusitaniae, 0.72 microgram/ml for C. parapsilosis, 0.78 micrograms/ml for C. krusei, and 1.25 micrograms/ml for C. guilliermondii. The results indicate that the new antifungal agent L-733,560 demonstrated the best activity with the lowest MICs against C. albicans, T. glabrata, C. tropicalis, and C. kefyr, less activity against C. krusei, C. lusitaniae, and C. parapsilosis, and the least activity against C. guilliermondii. L-733,560 also demonstrated good activity against the various multi-azole-resistant Candida and T. glabrata isolates.
PMCID: PMC163013  PMID: 8593003
14.  Effects of systemic cell-mediated immunity on vaginal candidiasis in mice resistant and susceptible to Candida albicans infections. 
Infection and Immunity  1995;63(10):4191-4194.
Studies to date with CBA/J mice suggest a limited role for systemic cell-mediated immunity (CMI) against vaginal Candida albicans infections. The results of the present study show that preinduced Candida-specific systemic CMI was equally nonprotective against C. albicans vaginal infections in mice with high (BALB/cJ), low (DBA/2), or intermediate (CBA/J) resistance to C. albicans infections. Similarly, the locally acquired partial protection against a second C. albicans vaginal infection was equally observed with BALB/cJ, DBA/2, and CBA/J mice. These results indicate that observations made previously with CBA/J mice were not murine strain specific and provide additional support for the hypothesis that systemic CMI does not represent a dominant host defense mechanism at the vaginal mucosa.
PMCID: PMC173593  PMID: 7558342
15.  Circulating CD4 and CD8 T cells have little impact on host defense against experimental vaginal candidiasis. 
Infection and Immunity  1995;63(7):2403-2408.
The etiology of recurrent vulvovaginal candidiasis in otherwise healthy women of child-bearing age remains an enigma. To date, results from both clinical studies and a murine model of vaginal candidiasis indicate that Candida vaginitis can occur in the presence of Candida-specific Th1-type cell-mediated immunity expressed in the peripheral circulation. The present study was designed to determine the role of circulating CD4 and CD8 cells in primary and secondary vaginal infections with Candida albicans. Vaginal fungal burden, Candida-specific delayed-type hypersensitivity (DTH), and lymph node cell Th1/Th2 cytokine production were monitored in CD4 and/or CD8 cell-depleted mice during persistent primary vaginal infections and secondary vaginal infections against which partial protection was observed. Treatment of mice with anti-CD4 or anti-CD8 antibodies resulted in 90% or greater depletion of the respective cell populations. Mice depleted of CD4 cells had significantly reduced Candida-specific DTH and lymph node cell Th1-type cytokine production during a primary vaginal infection, as well as reduced anamnestic DTH during a secondary vaginal infection. In contrast, mice depleted of CD8 cells showed only reduced gamma interferon production during a primary infection; no alterations in DTH were observed. Despite reductions in DTH and cytokine production, however, CD4 and/or CD8 cell depletion had no effect on vaginal C. albicans burden in mice after a primary or secondary vaginal inoculation. Taken together, these results suggest that while circulating CD4 and CD8 cells contribute to systemic Candida-specific cell-mediated immunity in vaginally infected mice, neither CD4 nor CD8 circulating T cells appear to provide significant host defenses against C. albicans at the vaginal mucosa.
PMCID: PMC173321  PMID: 7790050
16.  Mice immunized by primary vaginal Candida albicans infection develop acquired vaginal mucosal immunity. 
Infection and Immunity  1995;63(2):547-553.
It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense mechanism against Candida infections of the vagina. However, in an estrogen-dependent murine model of experimental vaginal candidiasis, we recently showed that systemic Candida-specific Th1-type CMI induced by immunization with Candida culture filtrate antigen had no effect on vaginal Candida population levels during the course of a vaginal infection. In the present study, mice given a second vaginal inoculation in the presence of peripheral Candida-specific Th1-type CMI induced by prior vaginal infection had anamnestic-type increased delayed-type hypersensitivity (DTH) responses, concomitant with significantly fewer Candida organisms in the vagina than in primary-infected mice. In addition, organisms in secondary-infected mice were fragmented and superficial penetration into the epithelium was reduced. The systemic presence of Candida-specific T suppressor (Ts) cells that significantly suppressed the infection-derived anamnestic DTH reactivity did not abrogate the protective effect in the vagina. Additional experiments showed that vaginally immunized mice were not protected from gastrointestinal or systemic candidiasis and, in contrast to mice with a second vaginal infection, did not demonstrate anamnestic DTH reactivity. These results suggest that a moderate level of local protection against a Candida vaginal infection can be achieved by vaginal immunization but that the protective role of acquired peripheral Candida-specific Th1-type reactivity at the vaginal mucosa appears to be limited.
PMCID: PMC173030  PMID: 7822020
17.  Systemic lupus erythematosus, Sjögren's syndrome and glomerular nephritis. 
Postgraduate Medical Journal  1977;53(616):97-101.
The combination of systemic lupus erythematosus, Sjögren's disease and severe diffuse glomerular nephritis has only rarely been reported. A 14-year-old girl is described with lupus nephritis in whom co-existent clinical and histological features of Sjögren's syndrome were found. These include bilateral parotid enlargement, xerostomia, increased serum amylase, reduced salivary secretion and lymphocyte infiltration of both salivary glands and kidneys. The co-existence of systemic lupus erythematosus with Sjögren's syndrome is discussed together with a consideration of pathogenesis.
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PMCID: PMC2496633  PMID: 876928
18.  Polymorphonuclear leucocyte function in Behçet's disease. 
Journal of Clinical Pathology  1977;30(3):250-253.
Polymorphonuclear leucocyte function was investigated in 19 patients with active Behçet's disease. Spontaneous free leucocyte migration was found to be significantly reduced, yet after stimulation the leucocyte's chemotactic activity was considerably increase (p less than 0-05) when compared to control leucocytes. Control leucocytes migrated more rapidly when incubated in serum taken from patients with Behçet's disease (p less than 0-005). The enhanced chemotactic activity in Bechçet's disease appears to be due to both serum and intrinsic leucocyte factors. Spontaneous nitroblue tetrazolium reduction was found to be normal, although after stimulation leucocyte nitroblue tetrazolium reduction was lower than in the control group (P less than 0-025), as was leucocyte oxygen utilisation. It is suggested that the hyperreactive cellular inflammatory response that characterises Behçet's disease may be due to increased chemotactic activity and minor alterations in functional metabolic activity of leucocytes.
PMCID: PMC476367  PMID: 845272
19.  Pancreatic ascites treated by irradiation of pancreas. 
British Medical Journal  1971;2(5760):503-504.
PMCID: PMC1795970  PMID: 5579494
20.  Comparison of bacterial and fungal adherence to vaginal exfoliated epithelial cells and human vaginal epithelial tissue culture cells. 
Infection and Immunity  1982;35(2):697-701.
The adherence of four bacterial species and Candida albicans to a new in vitro tissue culture model of human vaginal stratified squamous epithelium was investigated and compared with in vitro adherence to vaginal exfoliated cells. Gardnerella vaginalis, group B streptococci, Lactobacillus sp., and C. albicans adhered well to both exfoliated and tissue culture cells. Similarly, a piliated fecal isolate of Escherichia coli, but not a nonpiliated vaginal isolate of E. coli, adhered well to both cell types. Adherence of the piliated E. coli was markedly inhibited by preincubation of bacteria with D-mannose. No inhibition of adherence by D-mannose of G. vaginalis, nonpiliated E. coli, and C. albicans was demonstrated. Scanning electron microscopy of tissue cultures showed nonuniform distribution of adherent microorganisms with diminished adherence in areas of active mitosis and proliferation and increased adherence to mature flat cells, often in the process of desquamation.
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PMCID: PMC351097  PMID: 6120141
21.  Effects of preinduced Candida-specific systemic cell-mediated immunity on experimental vaginal candidiasis. 
Infection and Immunity  1994;62(3):1032-1038.
It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense factor against recurrent vaginal infections caused by Candida albicans. Using an estrogen-dependent murine model of vaginal candidiasis, we have previously shown that mice inoculated vaginally with C. albicans acquire a persistent vaginal infection and develop Candida-specific Th1-type systemic CMI. In the present study, experimental vaginitis was monitored in the presence of preinduced systemic Candida-specific CMI. Mice immunized systemically with C. albicans culture filtrate antigens (CaCF) in complete Freund's adjuvant (CFA) had Th1-type reactivity similar to that of vaginally infected mice. CaCF given to mice intravenously induced Candida-specific suppressor T (Ts) cells. Mice preimmunized with CaCF-CFA and given a vaginal inoculum of C. albicans had positive delayed-type hypersensitivity (DTH) reactivity from the time of vaginal inoculation through 4 weeks. Conversely, mice infected in the presence of Ts cells had significantly reduced DTH responses throughout the 4-week period in comparison with naive infected mice. However, the presence of Th1-type Candida-specific DTH cells or Ts cells, either induced in mice prior to vaginal inoculation or adoptively transferred at the time of inoculation, had no effect on the vaginal Candida burden through 4 weeks of infection. A similar lack of effects was obtained in animals with lower Candida population levels resulting from a reduction in or absence of exogenous estrogen. These results suggest that systemic Th1-type CMI demonstrable with CaCF is unrelated to protective events at the level of the vaginal mucosa.
PMCID: PMC186220  PMID: 8112837
22.  Candida-specific Th1-type responsiveness in mice with experimental vaginal candidiasis. 
Infection and Immunity  1993;61(10):4202-4207.
The role of systemic cell-mediated immunity (CMI) as a host defense mechanism in the vagina is poorly understood. Using a murine pseudoestrus model of experimental vaginal candidiasis, we previously found that animals given a vaginal inoculum of viable Candida albicans blastoconidia acquired a persistent vaginal infection and developed Candida-specific delayed-type hypersensitivity (DTH) responses. The present study was designed to characterize the peripheral CMI reactivity generated from the vaginal infection in mice and to determine whether pseudoestrus is a prerequisite for the induction of peripheral CMI reactivity. Mice treated or not treated with estrogen and given a vaginal inoculum of C. albicans blastoconidia were examined for 4 weeks for their vaginal Candida burden and peripheral CMI reactivity, including DTH responsiveness and in vitro Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma]/Th2 (IL-4, IL-10)-type lymphokine production in response to Candida antigens. Results showed that although mice not treated with estrogen before being given a vaginal inoculum of C. albicans blastoconidia developed only a short-lived vaginal infection and harbored significantly fewer Candida CFU in the vagina compared with those given estrogen and then infected; DTH reactivity was equivalent in both groups. In vitro measurement of CMI reactivity further showed that lymph node cells from both estrogen- and non-estrogen-treated infected mice produced elevated levels of IL-2 and IFN-gamma in response to Candida antigens during the 4 weeks after vaginal inoculation. In contrast, lymph node cells from the same vaginally infected mice showed no IL-10 production and only small elevations of IL-4 during week 4 of infection. These results suggest that mice with experimental vaginal candidiasis develop predominantly Th1-type Candida-specific peripheral CMI reactivity and that similar patterns of Th1-type reactivity occur in mice regardless of the persistence of infection and the estrogen status of the infected mice.
PMCID: PMC281145  PMID: 8406809
23.  Comparison of restriction enzyme analysis versus pulsed-field gradient gel electrophoresis as a typing system for Torulopsis glabrata and Candida species other than C. albicans. 
Journal of Clinical Microbiology  1993;31(8):2021-2030.
Candida species have recently emerged as important nosocomial pathogens. Because of the lack of a reliable system for detecting differences within the same species, little is known about the epidemiology of infection with Candida species. We describe a typing system for Torulopsis glabrata and the non-C. albicans Candida species that uses contour-clamped homogeneous electric field electrophoresis (CHEF), a version of pulsed-field gradient gel electrophoresis, and compared it with restriction enzyme analysis (REA) of genomic DNA. One hundred seventeen clinical isolates from 40 patients were evaluated. CHEF and REA were performed on each of the isolates, and the results of the two procedures were compared. The REA procedure revealed 8 different types of Candida lusitaniae, 20 of Torulopsis glabrata, 5 of Candida tropicalis, 3 of Candida parapsilosis, and 7 of Candida kefyr, whereas the CHEF method revealed 14 different types of C. lusitaniae, 16 of T. glabrata, 10 of C. tropicalis, 10 of C. parapsilosis, and 7 of C. kefyr. The CHEF technique yielded unique patterns of electrophoretic karyotypes that could be used to distinguish intraspecies variations. When compared with REA, CHEF demonstrated greater sensitivity in recognizing subtle strain-to-strain variations in most isolates and will be a useful epidemiologic tool for studying non-C. albicans Candida species and T. glabrata.
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PMCID: PMC265690  PMID: 8396585
24.  Candida-specific cell-mediated immunity is demonstrable in mice with experimental vaginal candidiasis. 
Infection and Immunity  1993;61(5):1990-1995.
Women with recurrent vulvovaginal candidiasis often demonstrate a down-regulation of cell-mediated immunity (CMI) to Candida albicans detected by a lack of cutaneous delayed-type hypersensitivity (DTH) to Candida antigens. However, the role of systemic CMI as a host defense mechanism against recurrent vulvovaginal candidiasis is not well understood, in part because of the lack of a well-defined murine model of vaginal candidiasis. The present study was undertaken to determine: (i) whether soluble Candida culture filtrate antigens (CaCF) could be used to induce and detect Candida-specific CMI in mice and (ii) whether these antigens would be useful in detecting systemic CMI in mice given an experimental Candida vaginal infection. To this end, mice were immunized subcutaneously with CaCF in complete Freund's adjuvant, and within 7 days they developed Candida-specific DTH reactivity detected by footpad swelling (increase in footpad thickness, 0.36 mm) 24 h after footpad challenge with CaCF. Adoptive transfer studies showed that the DTH responsiveness was elicited by CD4+ DTH T cells. In mice given a vaginal inoculum of C. albicans blastoconidia (5 x 10(5)), footpad challenge with CaCF resulted in positive DTH responses (0.24 mm) as early as 1 week, responses similar to immunization in 2 to 3 weeks (0.33 mm), and sustained low levels of DTH reactivity (0.15 mm) through 10 weeks of vaginal infection. Vaginal lavage cultures revealed that peak vaginal Candida burden occurred 1 week post-vaginal inoculation (10(5) CFU) and declined 16-fold by week 10. These results provide evidence that Candida-specific systemic CMI is generated and can be detected longitudinally in mice with Candida vaginitis by a multiantigen preparation of Candida organisms which both initiates and detects Candida-specific CMI.
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PMCID: PMC280793  PMID: 8097493
25.  Epidemiology of nosocomial acquisition of Candida lusitaniae. 
Journal of Clinical Microbiology  1992;30(11):3005-3008.
Candida species are important nosocomial pathogens; however, little is known about the epidemiology of Candida lusitaniae, an organism frequently resistant to amphotericin B. We evaluated 98 patients admitted to the bone marrow transplant and medical intensive care units of a tertiary-care hospital. Each patient with C. lusitaniae was matched with control patients. Restriction fragment analysis of DNA was used to determine strain relatedness. Seven patients (7.1%) with C. lusitaniae were identified; five acquired C. lusitaniae after admission to the study unit. All isolates were susceptible to amphotericin B. There were no differences between patients and controls with regard to duration of stay in the study unit, antibiotic administration, antifungal therapy, immunosuppressive therapy, catheter use, or underlying disease. Temporal and geographic clustering of five patients with identical strains occurred. No common source was identified. Restriction fragment analysis revealed a total of eight strains, and five patients shared one strain type. These results demonstrate exogenous acquisition of C. lusitaniae. The mechanism of acquisition is probably indirect contact transmission between patients.
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PMCID: PMC270571  PMID: 1360476

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