Congenital cutaneous candidiasis associated with maternal peripartum candidemia

BackgroundCutaneous congenital candidiasis (CCC) is a rare condition consisting of invasive fungal infection of the epidermis and dermis that mostly affects preterm infants. Maternal vaginal candidiasis is present in half of the cases, although the occurrence of invasive candidiasis during pregnancy or peripartum period is exceptional.Case reportWe present the case of a full-term infant that was born by vacuum-assisted vaginal delivery to an apparently healthy 33 year-old woman with no history of intravenous drug use or vaginal candidiasis during pregnancy. The newborn showed a diffuse maculopapular rash with respiratory distress and bilateral interstitial lung infiltrates, requiring nasal continuous positive airway pressure support. Blood cultures obtained from the mother due to intrapartum fever yielded Candida albicans. Cultures of vaginal discharge and neonate skin also yielded C. albicans with the same in vitro susceptibly pattern. No alternative source for candidemia was identified. The clinical course after starting a systemic antifungal therapy was favorable in both the mother and the neonate, with clearance of candidemia and resolution of the skin lesions.ConclusionsCCC must be considered in full-term newborns with maculopapular rash at birth or during the first days of life. The absence of alternative sources for bloodstream infection in the present case suggests a potential etiopathogenic relationship between CCC and maternal candidemia. It is reasonable to rule out postpartum candidemia when CCC is suspected.     

Host defense against oropharyngeal and vaginal candidiasis: Site-specific differences

Mucosal candidiasis is extremely common in immunocompromised patients. However, the prevalence of site-specific infection (i.e., oropharyngeal, vaginal, and esophageal candidiasis) can be quite variable depending on the immune status of the host. While vulvovaginal candidiasis is common in normal healthy women, oropharyngeal and esophageal candidiasis are more frequently encountered under immunocompromised states. Candida albicans, the causative agent in most cases of candidiasis, is a commensal organism of the gastrointestinal and lower female reproductive tracts. Thus, most healthy individuals have demonstrable Candida-specific immunity in the peripheral circulation. The pathogenic state is often precipitated by a deficiency or dysfunction in this immunity. Studies from animal models, women with recurrent vulvovaginal candidiasis, and HIV-infected individuals, however, suggest that distinct host defense mechanisms may function against oropharyngeal and vulvovaginal candidiasis. While cell-mediated immunity (CMI) appears important for protection against oropharyngeal candidiasis (OPC), there is little evidence to indicate that T cell-mediated immunity is protective against vulvovaginal candidiasis (VVC). Furthermore, whereas both local and systemically derived immune defenses appear important for protection against OPC, host defenses that protect against VVC appear limited to the local tissue and possibly restricted to innate mechanisms. Thus, current evidence suggests that VVC, unlike OPC, may not represent a strict opportunistic infection.     

念珠菌病的临床研究进展

念珠菌病是由念珠菌属的某些种群引起的条件致病真菌感染,是人类真菌感染性疾病中最多见的疾病。临床上分为浅部皮肤黏膜念珠菌病和深部念珠菌病（亦称系统性念珠菌病）。近年来深部念珠菌病的发病率有上升趋势,该病涉及临床各科室,危害性大,病死率高,是临床研究的热点。现复习近年国内外文献,就其致病念珠菌的动态流行病学、分子流行病学以及该病的实验室诊断进展及防治现状加以简要的介绍。     

Mouse model of oropharyngeal candidiasis

Oropharyngeal candidiasis is a frequent cause of morbidity in patients with defects in cell-mediated immunity or saliva production. Animal models of this infection are important for studying disease pathogenesis and evaluating vaccines and antifungal therapies. Here we describe a simple mouse model of oropharyngeal candidiasis. Mice are rendered susceptible to oral infection by injection with cortisone acetate and then inoculated by placing a swab saturated with Candida albicans sublingually. This process results in a reproducible level of infection, the histopathology of which mimics that of pseudomembranous oropharyngeal candidiasis in humans. By using this model, data are obtained after 5-9 d of work.     

The use of immunoenzyme analysis in the diagnosis of candidiasis in patients with different variants of hemoblastosis]

A total of 84 blood sera taken from patients with tumors of the hematopoietic system, among them 63 blood sera from patients with candidiasis and 21 blood sera from patients without symptoms of Candida infection have been tested in the enzyme immunoassay (EIA). This assay has been found suitable for the diagnosis of the visceral forms of candidiasis in patients with acute leukemia and hematosarcoma. EIA has proved to be an inadequate method for the detection of Candida infection in chronic lympholeukemia patients, as well as in patients with acute leukemia and hematosarcoma, suffering from such local forms of candidiasis as candidiasis of the oral cavity.     

Clinical spectrum of invasive candidiasis in critically ill non-neutropenic patients

Invasive Candida spp. infections in non-neutropenic critically ill patients admitted to intensive care units can be classified as focal and systemic. Both types of infection usually occur after episodes of candidemia, although some focal infections may be of exogenous development, like those occurring after trauma or be device-related.The clinical spectrum of invasive Candida spp. infections includes focal urinary tract, abdominal, ocular, respiratory tract, renal and hepato-biliary infections, as well as systemic infections like candidemia and acute systemic candidiasis with multiorgan involvement after hematogenous seeding. Candida spp. isolates in "significant" samples, like synovial fluid, cerebrospinal fluid and blood cultures, represent true infection. However, the diagnosis of invasive infection based on "non-significant" samples, like surgical drains and digestive tract exudates, requires additional criteria. The total number of isolates from different sites, the presence of risk factors, the clinical host response, as well as severity of illness need to be taken into account for the diagnosis of invasive candidiasis. The clinical signs of systemic infection due to Candida spp. are completely non-specific and cannot be differentiated from bacterial peritonitis, urinary tract infection or bacteremia. These infections may be associated with signs of sepsis,severe sepsis, septic shock or multiorgan dysfunction. In the future clinical multicentre observational and interventional studies are necessary to reach agreement on clinical definitions and classification of invasive Candida spp. infections in critically ill non-immunocompromised patients.     

The extent of immune response impairment vs. the prevalence and clinical form of oral candidiasis in HIV patients

The objective of the study was a mycological and clinical evaluation of the course of oral cavity fungal infection in HIV patients in relation to the immune response impairment. The patients were examined physically (symptoms and signs) and mycologically (isolation and identification of fungi, semiquantitative evaluation their growth abundance in the cultures); the immunity status was expressed in terms of the number of CD4 lymphocytes. The most frequently isolated fungal species was Candida albicans. The decreasing immunity was conductive to more abundant fungal growth in the oral cavity as well as to more frequent occurrence of clinical manifestations of candidiasis.     

Modulation of neutrophil function in host defense against disseminated Candida albicans infection in mice

Neutrophils (PMNs) constitute the main mechanism of host defense against acute invasive and disseminated candidiasis. Recent studies have demonstrated that tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) play an important role in the recruitment of PMNs at the site of invasive Candida infection. In the absence of either TNFalpha or IL-6, the course of experimental disseminated candidiasis is more severe, due to defective PMN recruitment. Treatment of mice with recombinant G-CSF (rG-CSF) leads to a significantly reduced mortality during disseminated candidiasis. The outgrowth of Candida albicans from the organs of rG-CSF-treated mice is significantly decreased. Treatment with the combination of rG-CSF and fluconazole has an additive effect on the reduction of fungal load in the organs. In subacute or chronic disseminated Candida infection, rG-CSF is less effective, indicating that neutrophil recruitment and activation are crucial in acute, life-threatening candidiasis, whereas other host defense mechanisms control the outcome of less overwhelming invasive Candida infection.     

Candidiasis: Predisposing Factors,Prevention, Diagnosis and Alternative Treatment

Candidiasis is the most common opportunistic yeast infection. Candida species and other microorganisms are involved in this complicated fungal infection, but Candida albicans continues to be the most prevalent. In the past two decades, it has been observed an abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts, not only in immunocompromised patients, but also related to nosocomial infections and even in healthy individuals. There is a widely variety of causal factors that contribute to yeast infection which means that candidiasis is a good example of a multifactorial syndrome. Due to rapid increase in the incidence in these infections, this is the subject of numerous studies. Recently, the focus of attention is the treatment and, above all, the prevention of those complications. The diagnosis of candidiasis could become quite complicated. Prevention is the most effective “treatment,” much more than eradication of the yeast with antifungal agents. There are several aspects to consider in the daily routine that can provide a strength protection. However, a therapeutic approach is necessary when the infection is established, and therefore, other alternatives should be explored. This review provides an overview on predisposition factors, prevention and diagnosis of candidiasis, highlighting alternative approaches for candidiasis treatment.     

体液免疫抗白念珠菌感染的研究

探讨抗白念珠菌IgY及其免疫血清对多种动物模型感染白念珠菌的保护作用。制备烧伤继发感染白念珠菌大鼠、白念珠菌性阴道炎小鼠及免疫功能低下小鼠多种动物感染模型 ,分别应用抗白念珠菌IgY、鼠免疫血清和生理盐水对照 ,观察比较各自的作用。抗白念珠菌IgY对烧伤继发感染白念珠菌大鼠及白念珠菌性阴道炎小鼠均有明显的保护作用 ;鼠免疫血清则对阻止远程靶器官的白念珠菌扩散有较好的作用。体液免疫成份抗白念珠菌IgY及其免疫血清对烧伤继发感染白念珠菌大鼠、白念珠菌性阴道炎小鼠及免疫功能低下小鼠均有良好的保护作用。     

Use of 65-kDa mannoprotein gene primers for real-time identification of Candida albicans

Invasive candidiasis is associated with high morbidity and mortality, especially in immunocompromised patients. Early diagnosis is often difficult because most clinical signs and symptoms are nonspecific and blood cultures are often negative or become positive too late. Consequently, effective treatment is often delayed. Therefore, there has been an increased interest in the development of molecular-based technology in the diagnosis of invasive candidiasis. In this review, we compare molecular diagnostic tests currently adopted and those under evaluation. We highlight the advantages and the limitations of these methods for the diagnosis of invasive candidiasis. We also describe recent methods based on real time with primers of a gene coding for a 65-kDa mannoprotein of Candida albicans.     

以皮肤受累为首发表现的播散性念珠菌病1例并文献复习

目的：播散性念珠菌病是一种致命性真菌感染性疾病,在免疫缺陷患者中发病率逐年增多,报道1例以双下肢多发皮下结节为首发表现,伴有肺及脑受累的播散性念珠菌病,并文献复习播散性念珠菌病的皮肤受累临床表现。方法患者女,37岁。因双下肢多发皮下结节6个月余就诊。有局灶节段性肾小球硬化病史,口服强的松及他克莫司2a余。取患者皮损组织行病理学检查,皮损组织、脓液、血、痰、尿、粪、脑脊液进行真菌镜检及真菌培养,并文献检索统计播散性念珠菌病皮肤受累患者临床特点。结果皮损组织病理见假菌丝,皮损组织、脓液、痰、尿、粪标本直接涂片均见假菌丝并培养出白念珠菌,CT显示肺受累,诊断为播散性念珠菌病,予抗真菌治疗,患者皮损愈合及肺部病灶部分吸收,但因自行停药,最终出现颅内播散。结论以皮损为首发表现的播散性念珠菌病临床罕见,临床诊疗中应重视应用免疫抑制剂患者皮损的组织病理及微生物检查,及早进行诊断和治疗,防止出现系统性播散,从而降低死亡率。     

The C-terminal antibody binding domain of Candida albicans mp58 represents a protective epitope during candidiasis

The 58-kDa surface mannoprotein of Candida albicans (mp58) elicits strong antibody responses during infection. Epitope mapping with sera from patients with candidiasis and control individuals indicated the presence of multiple IgG-reactive continuous epitopes on the protein, expanding both the amino- and carboxy-terminal domains and several internal regions. These immunoreactive regions were similar to the ones previously identified using sera from immunized animals. Two of the epitopic regions (including the C-terminal domain) showed increased reactivity with antibodies present in sera from patients with candidiasis as compared to control individuals. Patients who survived the infection displayed increased antibody reactivity towards the C-terminal epitope as compared to those succumbing to candidiasis. A monoclonal antibody directed towards this epitopic region conferred protection in serum therapy experiments in a murine model of hematogenously disseminated candidiasis. Together, these observations indicate the carboxy-terminal antibody binding domain of C. albicans mp58 represents a protective epitope during candidiasis.     

Insights from human studies into the host defense against candidiasis

Candida spp. are the most common cause of mucosal and disseminated fungal infections in humans. Studies using mutant strains of mice have provided initial information about the roles of dectin-1, CARD9, and Th17 cytokines in the host defense against candidiasis. Recent technological advances have resulted in the identification of mutations in specific genes that predispose humans to develop candidal infection. The analysis of individuals with these mutations demonstrates that dectin-1 is critical for the host defense against vulvovaginal candidiasis and candidal colonization of the gastrointestinal tract. They also indicate that CARD9 is important for preventing both mucosal and disseminated candidiasis, whereas the Th17 response is necessary for the defense against mucocutaneous candidiasis. This article reviews the recent studies of genetic defects in humans that result in an increased susceptibility to candidiasis and discusses how these studies provide new insight into the host defense against different types of candidal infections.     

Immune system function in candidiasis patients

To compare the clinical picture and the immunological characteristics, 58 candidiasis patients differing by the severity and dissemination of the disease were examined. Chronic candidiasis of the skin and mucous membranes, the most severe and disseminated form of the disease, is associated with a decrease in the number of T-lymphocytes and changes in their subpopulations, as well as high titers of Candida albicans antigen and antibodies to it in blood sera. The immune system of patients with visceral candidiasis and chronic vulvovaginal candidiasis was similar to that of healthy persons in the characteristics under study. Immediate and mixed hypersensitivity occurred in candidiasis patients more frequently than in healthy persons. In extremely severe forms of Candida infection immediate hypersensitivity prevailed.     

慢性阻塞性肺疾病并念珠菌性口炎患者病原学及危险因素分析

目的 探讨入院慢性阻塞性肺疾病(COPD)并念珠菌性口炎患者的病原学特征以及相关危险因素.方法 采用病例研究,对2007年4月1日至2011年1月31日入院的82例COPD并念珠菌性口炎患者和82例无念珠菌性口炎COPD患者进行匹配,应用SPSS 17.0统计软件行条件logistic回归模型分析COPD患者念珠菌性口炎发生的危险因素.结果 (1)从念珠菌性口炎患者假膜培养共分离出念珠菌83株,以白念珠菌(90.4％)为最多,其次为光滑念珠菌(3.6％)、克柔念珠菌(2.4％)、热带念珠菌(2.4％)、近平滑念珠菌(1.2％);(2)统计学分析结果显示全身应用、吸入糖皮质激素是入院患者口腔念珠菌感染的独立危险因素.结论 白色念珠菌是COPD患者口腔部念珠菌感染的主要病原菌,规范使用全身糖皮质激素、正确吸入糖皮质激素是预防COPD患者口腔念珠菌感染的关键.     

Kinetics of Anti-Mannan Antibodies Useful in Confirming Invasive Candidiasis in Immunocompromised Patients

In studying the anti-mannan antibodies longitudinally in serial serum samples of three immunocompromised patients, it was observed that anti-mannan antibodies started to increase shortly after the moment that cultures of deep-tissue sites became positive with Candida albicans. The mean anti-mannan antibody titers determined in a group of 36 immunocompromised patients with invasive candidiasis increased within two weeks after the probable onset of invasive candidiasis. In contrast, anti-mannan antibody levels in serial serum samples of 14 immunocompromised patients who were only colonized with C. albicans remained stable or decreased over time. The HA test measuring the anti-mannan antibodies was 64% sensitive and 89% specific in determining invasive candidiasis. In contrast, antibodies specific for candidal cytoplasmic antigens or enolase alone were of little value in confirming invasive candidiasis in these immunocompromised patients.     

Use and value of serologic tests for the diagnosis of systemic candidiasis in cancer patients: A prospective study of 146 patients

Sera from 146 cancer patients at risk for disseminated candidiasis were studied prospectively with immunodiffusion (ID), counterelectrophoresis (CEP), and latex agglutination (LA) tests to determine their diagnostic value in the detection of antibodies to theCandida species. Serial serum samples, cultures, and clinical data were obtained after a malignancy was diagnosed. Patients were classified into three groups (I, II, and III) on the basis of cultural, histological, and clinical evidence for superficial (Group I) versus disseminated (Group III)Candida infection. Thirty-two of 78 patients (41%) in Group I had positive ID, CEP, and LA titers. In Group II, those patients lacking histological confirmation of disseminated infection, 16 of 18 (89%) had positive titers. Thirty-six of 50 (72%) in Group III were positive by all three tests. Heavy colonization of the gastrointestinal tract, without evidence of tissue invasion, produced positive test results. Negative serologic tests were encountered in immunosuppressed patients with rapidly progressive candidiasis.C. krusei infections produced specific antibody titers detected by the homologous antigen but not byC. albicans antigen. Stable or decreasing LA titers were correlated with clinical improvement in patients receiving effective antifungal therapy.     

Defining criteria for anti-mannan antibodies to protect against candidiasis

Prevention of hematogenously disseminated candidiasis and mucocutaneous disease, including Candida vaginitis, through immunological approaches is appealing for the following reason. A long-acting and safe vaccine that protects against both serotypes of Candida albicans and other important species, such as C. tropicalis and C. glabrata, should significantly reduce the incidence of various forms of candidiasis by these etiologic agents. Through extensive experimentation on protective responses in experimental animals against Candida mannan components, others and we have evidence that antibodies specific for short-chain beta-linked oligomannosides are protective against candidiasis. Although the mechanism of protection against vaginal infection requires further investigation, experimentally the ability of antibody to rapidly deposit high amounts of complement factor C3 onto the yeast cell wall is requisite for enhancing resistance against disseminated candidiasis.     

Mannan and D-arabinitol concentrations in serum from a patient with Candida albicans endocarditis

In an attempt to clarify the comparative values of serological and microbiological examinations for the early diagnosis of systemic candidiasis, antibodies against Candida albicans, serum mannan, and the D-arabinitol creatinine ratio were investigated in a patient with aortic valve endocarditis associated with carcinoma of the bile duct. Candida precipitins and the antibody titer against Candida cell wall mannan were examined by an immunodiffusion technique and hemagglutination test, respectively. Serum mannan was tested by enzyme-linked immunosorbent assay (ELISA) using the biotin-streptavidin procedure. The upper limit of negativity of the assay was determined by adding 0.06 to the absorbance of pooled serum from healthy laboratory workers. This value ws about 0.8 ng/ml with ELISA. The D-arabinitol concentration in serum was examined by an enzymatic fluorometric method. Rising antibody titers against C. albicans, mannan antigenemia, and an elevated D-arabinitol creatinine ratio were first observed between the 11th and 12th hospital days. Blood cultures obtained on 8th, 9th, and 11th hospital days grew C. albicans after 3 to 4 days of incubation. Of 11 serum samples, 5 were positive for mannan, whereas D-arabinitol creatinine ratio was positive in 7 of 9 samples. Blood cultures was the earliest evidence of Candida infections in our cases. However, because of saprophytic nature of Candida species, tests for antibodies, antigenemia, and the D-arabinitol creatinine ratio in combination with blood cultures are necessary to confirm systemic candidiasis at an early stage of infection.Abbreviations ELISA enzyme-linked immunosorbent assay