Table of Content

28 October 2019, Volume 14 Issue 5

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Original articles

Distribution characteristics of invasive fungal infections in Hebei province from 2016 to 2017

LI Fang, LI zhi-rong, ZHAO Jian-hong, ZHAO Ying, ZHANG Yan-hai, DONG Ai-ying, LIU Jin-lu, GUO Yan-yan, SUN Yan, ZHAO Wen-shen, XIE Shou-jun, WEI Hong-lian, ZHANG Jin-yan, REN Hong-tao, WANG Jian-sheng, WU Xiang-kun, GUANG Xiao, LI Dong-qing, DU Hong-li, GUO Ying-hui, XU Ying-chun, XIAO Meng, YANG Wen-Hang, XU Xiao-lin

2019, 14(5):  257-263. 

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Objective To expore distribution characteristics of invasive fungal infections in 16 tertiary teaching hospitals in Hebei from 2016 to 2017, and to provide data for clinical diagnosis, treatment and infection control. Methods The yeast fungi and filamentous fungi causing invasive fungal infections were collected by member units. The strains were re-examined by Vitek MS analysis in the central laboratory. For difficult and rare strains, ITS and/or calmodulin CaM sequencing were used. Results A total of 493 invasive fungi strains were detected in 16 hospitals from 2016 to 2017, including 268 yeast fungi (54.36%) and 225 filamentous fungi (45.64%). Yeast fungi include 112 strains of C. albicans (41.79%), 52 strains of C. tropicalis (19.40%), 38 strains of C. parapsilosis (14.18%), 29 strains of C. glabrata (10.82%), 10 strains of Cryptococcus neoformans (3.73%) and 27 strains of other Candida (10.07%). Filamentous fungi included 131 strains of Aspergillus fumigatus (58.22%), 24 strains of Aspergillus flavus/Aspergillus oryzae (10.67%), 18 strains of Aspergillus Niger (8.00%), 6 strains of Aspergillus sydowii (2.67%), 5 strains of Aspergillus nestoris (2.22%) and 41 strains of other filamentous fungi (18.22%). The correct rate of invasive fungi identification was 75.66% (373/493). Conclusion The most common invasive fungal infections were Candida-dominated yeasts and Aspergillus-dominated filamentous fungi. The combination of microbial mass spectrometry identification and ITS/CaM region sequencing could effectively improve the identification accuracy of fungi and provide a reference for clinical treatment of invasive fungi.

Clinical application and evaluation oftwo different methods for detection of cryptococcal capsular polysaccharide antigen in diagnosis and treatment of pulmonary cryptococcosis

HUANG Jin-bao, LI Hong-yan, LAN Chang-qing, LV Xiao, LIN Zhi-lai, WANG Xin-hang, ZHANG Hong-ying, ZOU Sheng-hua, WEN Heng

2019, 14(5):  264-269. 

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Objective To evaluate lateral flow assay (LFA) and enzyme-linked immunesorbent assay (ELISA) for detection of cryptococcal capsular polysaccharide antigen (CrAg) in diagnosis and treatment of pulmonary cryptococcosis (PC). Method One hundred and nine cases of suspected PC were collected from January 2016 to June 2018 at Fuzhou Pulmonary Hospital of Fujian.Serum CrAg was detected by ELISA and LFA at the same time, and the diagnostic efficiency of the two methods for PC was compared and analyzed. Serum CrAg concentration was also monitored by ELISA during the treatment. Results Among the 109 patients, 53 cases were confirmed as PC by lung biopsy or cryptococcus detection of lung puncture liquid,56 cases were other lung diseases (Non-PC). The results were as follows:(1) The serum CrAg concentration detected by ELISA in the PC group was[11.43 (5.92, 47.96)] μg/L. The number of cases with serum CrAg ≤ 3.2 μg/L in the PC group was significantly lower than that in the non-PC group (P<0.05), while the number of cases with serum CrAg>5.0 μg/L was significantly higher than that in the non-PC group (P<0.05). The positive rate of serum CrAg detected by LFA in the PC group was significantly higher than that in the non-PC group, and the difference was statistically significant (P<0.05). (2) Receiver Operating Characteristic (ROC) curve analysis showed that the area under the curve of serum CrAg detected by ELISA was 0.939 (95% confidence interval was 0.892~0.985), and 3.54 μg/L was considered as the best cut-off value with the highest Youden index. The sensitivity, specificity, positive predictive value and negative predictive value were 94.3%, 80.4%, 82.0% and 93.8%, respectively. When 5.0 μg/L was taken as the diagnostic cut-off value of serum CrAg, there was no statistical difference in the diagnostic sensitivity between ELISA and LFA (88.7% vs 83.0%, P>0.05), but the specificity of ELISA test (82.1%) was significantly lower than that of LFA test (98.2%), and the difference was statistically significant (P<0.05). The diagnostic sensitivity and specificity of ELISA and LFA were similar (P>0.05) when the cut-off values of serum CrAg were 5.0μg/L, 6.0μg/L and 7.0 μg/L, respectively. The diagnostic sensitivity (62.3%) of ELISA was significantly lower than that of LFA (83.0%) when 8.0 μg/L was taken as the cut-off value of serum CrAg (P<0.05), but the specificity (100% and 98.2%) in the two methods was the same (P>0.05). (4) The serum CrAg concentration was continually monitored in 14 patients during the antifungal therapy. After six months of treatment, the serum CrAg was significantly decreased[19.33 (7.11, 43.46) vs 8.09 (5.39, 11.90) μg/L, P<0.05]. Conclusions 3.54 μg/L was considered as the best diagnostic cut-off value of serum CrAg of ELISA test. However, when 5.0 μg/L was taken as the diagnostic cut-off value, ELISA had good diagnostic sensitivity and specificity similarly to those of LFA, and the two methods had the same diagnostic efficiency. ELISA and LFA were both helpful to the rapid diagnosis of PC and worthy of being widely applied in clinic. Compared with LFA qualitative detection, ELISA could dynamically monitor the changes of serum CrAg concentration, which was useful for the treatment response and prognosis evaluation of PC.

Meta-analysis of the efficacy and safety of naftifine hydrochloride and ketoconazole cream for the dermatomycoses

FU Jie, WU Bin

2019, 14(5):  270-276. 

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Objective To evaluate the efficacy and safety of naftifine hydrochloride and ketoconazole cream for the dermatomycoses. Methods Searching for database about randomized controlled trials(RCT) of naftifine hydrochloride and ketoconazole cream and other antifungal drug monotherapy to treat the dermatomycoses in Cochrane Library, Medline, Embase, CBM, CNKI, VIP database, Wanfang database. Literature screening and data extraction was conducted in software NoteExpress. Meta-analysis was performed with RevMan5.3. Results Finally, 43 RCTs were included with a total of 5413 patients. The analysis showed that the effective rate of naftifine hydrochloride and ketoconazole cream was 85.27%. The analysis showed that the efficacy of naftifine hydrochloride and ketoconazole cream was better than that of miconazole nitrate[RR=1.32, 95% CI (1.26, 1.38)], bifonazole treatment for 4-week group[RR=1.31, 95% CI (1.12, 1.54)], and ketoconazole[RR=1.25, 95% CI (1.14, 1.36)]. Compared with other drugs, naftifine hydrochloride and ketoconazole cream had lower relapse rate and incidence of adverse reactions. Conclusions Naftifine hydrochloride and ketoconazole cream is effective and safe in the treatment of dermatomycoses.

Traditional herb lotion combined with topical antifungal therapy in the treatment of Malassezia folliculitis

ZHU Hong-mei, LIANG Xiao-bo, WEN Hai, LI Bin

2019, 14(5):  277-279. 

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Objective To evaluate the effect of traditional Chinese herb lotion combined with topical antifungal cream in the treatment of Malassezia folliculitis. Methods The cases of Malassezia folliculitis were divided into three groups. Group A:Anshuye lotion combined with 1% bifonazole cream, once daily; Group B:Pifukang lotion combined with 1% bifonazole cream, once daily; Group C:1% bifonazole cream, once daily; the duration of three groups was 4 weeks. Results After 4 weeks treatment, the total effective rates of three groups were 75.00%, 78.95% and 56.52% respectively. Conclusion Both two traditional herb lotions could significantly improve the therapeutic efficiency of topical antifungal treatment of Malassezia folliculitis.

Exploration of bronchoalveolar lavage fluid GM test standardized by internal reference in the diagnosis of invasive pulmonary aspergillosis

QIU Ju, CHEN Qian, HUANG Lin, XIA Ji-rong

2019, 14(5):  280-283. 

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Objective To to choose and standardizeinternal reference of bronchoalveolar lavage fluid galactomannan detection(BALF GM test), and to investigatewhether the BALF GM test after standardizing could improve the clinical diagnostic efficiency for invasive pulmonary aspergillosis(IPA). Methods A total of 156 BALF specimens were collected from The First Affiliated Hospital of Chongqing Medical University from May 2018 to January 2019. All samples were performed GM test and the levels of potassium, urea and albumin were measured. According to histopathology, microbiological results, clinical symptoms and characteristics, host factors and other data, all patients were divided into two groups:IPA group(39 cases) and non-IPA group(117 cases).The clinical diagnostic efficiencies of standardized and non-standardized BALF GM tests for IPAwere compared. Results The I values of the standardized and non-standardized BALF GM tests were both significantly different between two groups(P<0.001).The ROC curves showed that the cut-off value of the non-standardized BALF GM test was 0.69, the area under the curve was 0.731(P<0.001), the sensitivity was 71.8%, and the specificity was 70.1%. After standardizing by K⁺, UREA, and ALB, the cut-off values were 0.605, 1.905, 0.69, and the areas under the curve were 0.71, 0.653,0.701, respectively(P<0.001, 0.004, 0.002, respectively).The sensitivities were 74.4%, 66.7%, 69.2%,and the specificities were 70.9%, 63.2%, 69.8%, respectively. Conclusion With the cut-off value of 0.69,the non-standardized BALF GM test hadthe best diagnostic efficiency for IPA. The diagnostic efficiency of the BALF GM test after standardizing by K⁺ for IPA wasbetter than the non-standardized BALF GM test(P<0.001).

Detecting galactomannan in bronchoalveolar lavage fluid for diagnosing invasive pulmonary aspergillosis: a meta-analysis

CAI Kai-xia, ZHOU Jing, CAO Wei, WANG Sheng-yu

2019, 14(5):  284-291. 

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Objective To evaluate the diagnostic accuracy of bronchoalveolar lavage fluid (BALF) galactomannan (GM) for invasive pulmonary aspergillosis (IPA) and determine the optimal cut-off value by meta-analysis. Methods The Pubmed, EMBASE, OVID, Cochrane Library, CNKI(China National Knowledge Infrastructure),WANFANG,CBM(China Biology Medicine) databases were searched for relevant studies published in all languages up until October 31, 2018. Twenty-six studies (71 sets of data) meeting the criteria were included in this meta-analysis, conducted quality evaluation and heterogeneity analysis. Then, the pooled indicators of each diagnostic cut-off value, drew the receiver operating characteristic (ROC) curve were analyzed and calculated, and finally the optimal diagnostic cut-off was determined. Results The summary estimates of pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the BALF-GM (cut-off value 0.5) for the diagnosis of IPA (proven and probable IPA) were 0.87 (95% CI 0.84-0.89), 0.79 (95% CI 0.77-0.81), 4.60 (95% CI 3.49-6.05), 0.19 (95% CI 0.14-0.25), 38.84 (95% CI 22.99-52.81).The area under the curve (AUC) of the summary receiver operating characteristics (SROC) was 0.92 (95% CI 0.90-0.95). When the BALF-GM diagnostic cutoff value in 1.0, the area under curve(AUC) of the summary receiver operating characteristic (SROC) was a maximum of 0.94 (95% CI 0.93-0.97). Conclusions BALF GM was easy to detect and had high diagnostic accuracy for IPA. It could be used for diagnosis of IPA early, so as to implement early treatment and reduce mortality. At present, the recommended diagnostic cut-off was 1.0.

In vitro evaluation of inhibitory effect and mechanism of various lasers on Trichophyton rubrum under different energies

XIONG Ying, CHEN Ting, CHAI Bao, ZENG Fei-peng, SUN Wen-wen, WU Bo

2019, 14(5):  292-296. 

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Objective To investigate inhibitory effect of various lasers on Trichophyton rubrum under different energies, and explore the possible mechanism. Methods Plates of standard size of T.rubrum colonies were assigned as control or experimental Groups. Experimental group was irradiated by different lasers, which including Q-switched Nd:YAG 532nm laser, Q-switched Nd:YAG 1064nm laser, long pulse width Nd:YAG 1064nm laser and intense pulsed light. The effects of different lasers energies on isolated colonies were assessed. After irradiation, the sizes of colonies were measured at 1^st, 3^rd and 7^th days, the degree of keratinase production was measured by enzyme-linked immunosorbent assay. Results Compared with the control group, low power lasers did not have any inhibitory effect on the growth and keratinase production of Trichophyton rubrum. Q-switched Nd:YAG 532nm laser at 2-4J/cm²,Q-switched Nd:YAG 1064nm laser at 4-8J/cm² and long pulse width Nd:YAG 1064nm laser at 4J/cm² could significantly inhibit the growth of colonies and the production of keratinase. Conclusion Growth of T.rubrum and the production of keratinase could be effectively suppressed by Q-switched Nd:YAG 532nm laser at 2-4J/cm², Q-switched Nd:YAG 1064nm laser at 4-8J/cm² and long pulse width Nd:YAG 1064nm laser at 4J/cm².

Establishment of a real time PCR method for detecting Sporothrix brasiliensis

ZHANG Ming-rui, ZHOU Ying, LIFu-qiu, YAO Chun-li, YANG Xin, GONG Jie, ZHAO Fei

2019, 14(5):  297-302. 

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Objective To establish a rapid, specific and sensitive real-time PCR method for the detection of Sporothrix brasiliensis. Methods The internal transcribed spacer (ITS) sequence of S. brasiliensis were downloaded from the NCBI database. The conserved regions were obtained by software comparison. Specific primers and probes were designed and synthesized to establish and optimize the real time PCR method. The optimized method was used to evaluate amplification efficiency, sensitivity, and specificity using standard concentration nucleic acids. The method in this study was evaluated by mouse infection model of S. brasiliensis and compared with culture. Results The detection limit of the real-time PCR method established in this study for S. brasiliensis was 100 fg. The method was negative for the amplification of S. shenckii, S. globosa, 28 other common pathogenic fungi, 3 common bacteria, human genome and mouse genome, and the specificity was 100%. The detection results of the method and culture of brain, liver, lung, spleen, kidney and lymph nodes in mice infected with S. brasiliensis were consistent. Conclusion The real time PCR method established in this paper is a rapid, sensitive and specific method for the identification of S. brasiliensis. It can also detect specimens of infected mouse models, which is helpful for early diagnosis of sporotrichosis caused by S. brasiliensis.

Eosinophilic pustular folliculitis caused by Phoma sp

SUN Yi-dan, LI Xin-yue, SUN Ting-ting, et al

2019, 14(5):  303-307. 

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Advances in diagnosis and treatment of Talaromyces marneffei in patients with acquired immunodeficiency syndrome

ZHOU Yi-hong, LU Yan-qiu, CHEN Yao-kai

2019, 14(5):  308-312. 

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In recent years, some progresses had been made in early diagnosis and antifungal therapy of Talaromyces marneffei infection in acquired immunodeficiency syndrome (AIDS). In early clinical diagnosis, double-antibody sandwich ELISA and fluoroimmunoassay were suitable for assistant diagnosis in clinical acute stage and both were regarded highly specific. However, the two methods combining did not increase sensitivity and specificity further. Galactomannan and plasma(1-3)-β-D glucan measurement also had some early diagnostic value for Talaromyces marneffei in patients with AIDS. Sensitivity of fluorescence quantitative PCR was significantly higher than Nest's PCR method in detecting Talaromyces marneffei inparaffin embedded tissue samples, but its specificity was lower. In the treatment of Talaromyces marneffei, amphotericin B was the first choice during the induction period, and its antifungal efficacy was significantly better than that of itraconazole, although the incidence of adverse effects of the former was higher. Voriconazole and posaconazole had shown good results in retrospective studies as well as in vitro tests, and the clinical application value of the two methods still needed further study.

Advance on Traditional Chinese Herb in the topical antifungal therapy

ZHU Hong-mei, WEN Hai, LI Bin

2019, 14(5):  316-320. 

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Advance on topical antifungal traditional Chinese herb mainly focused on the following aspects:clinical application of empirical traditional Chinese medicinal formulae, identification and purification of monomers with antifungal function, in vitro antifungal sensitivity assay of monomers, in vivo application of new Chinese herb formulae or compound monomers products on the animal models of superficial mycosis, etc. The herbs themselves and their active ingredients might show direct or synergistic antifungal effects. Furthermore, they might reduce inflammation and relieve itching symptom through their traditional "Heat-Clearing and Dampness-Removing and Itching-Relieving" mechanisms. While eliminating some pathogenic fungi, they also made the local body microenvironment not beneficial for fungal growth.