Epidemiologic differences between the two varieties of Cryptococcus neoformans

This report of the worldwide distribution of two varieties of Cryptococcus neoformans was drawn from data on 628 clinical isolates and from data on 97 additional isolates from other laboratories. Tests showed that 100% of the cultures from Austria, Belgium, Denmark, France, Germany, Holland, Italy, Switzerland, and Japan belonged to C. neoformans var. neoformans. More than 85% of the isolates from Argentina, Canada, the United Kingdom, and the United States (except southern California) were of C. neoformans var. neoformans, the remainder being of C. neoformans var. gattii . There was an unusually high prevalence (35-100%) of C. neoformans var. gattii in Australia, Brazil, Cambodia, Hawaii, southern California, Mexico, Paraguay, Thailand, Vietnam, Nepal, and countries in central Africa. These findings indicated that C. neoformans var. gattii is prevalent only in tropical and subtropical regions. Seventy per cent of the total isolates studied were of serotype A of C. neoformans var. neoformans. Serotype D (9% of the total) was common in Europe, but was found infrequently in other regions. Among the two serotypes of C. neoformans var. gattii , serotype B was 4.5 times more prevalent than serotype C. The majority (88%) of type C isolates in our collection were from southern California.     

Cryptococcus neoformans strains and infection in apparently immunocompetent patients, China

To determine the population structure of the cryptococcosis agents in China, we analyzed the genotype of 120 Cryptococcus neoformans and 9 Cryptococcus gattii strains isolated from 1980 through 2006 from cryptococcosis patients residing in 16 provinces of mainland China. A total of 71% (91/129) of the clinical strains isolated from 1985 through 2006 were from patients without any apparent risk factors. Only 8.5% (11/129) were from AIDS patients; the remaining 20.5% (27/129) were from patients with underlying diseases other than HIV infection. One hundred twenty of the 129 isolates were C. neoformans serotype A, mating type MATalpha strains that exhibited an identical M13-based VNI subtype, which was distinguishable from the reference VNI molecular type. The 9 remaining isolates were serotype B, MATalpha strains of C. gattii and portrayed a typical VGI molecular type. Data analyzed from multilocus sequences showed no variation and that these Chinese C. neoformans isolates belong to a cluster that has phylogenetically diverged from the VNI reference strain. Our finding that most cryptococcosis patients in China had no apparent risk factor is in stark contrast with reports from other countries.     

AIDS patient death caused by novel Cryptococcus neoformans x C. gattii hybrid

Interspecies hybrids of Cryptococcus neoformans and C. gattii have only recently been reported. We describe a novel C. neoformans x C. gattii hybrid strain (serotype AB) that was previously described as C. gattii and that caused a lethal infection in an AIDS patient from Canada.     

Molecular typing of IberoAmerican Cryptococcus neoformans isolates

A network was established to acquire basic knowledge of Cryptococcus neoformans in IberoAmerican countries. To this effect, 340 clinical, veterinary, and environmental isolates from Argentina, Brazil, Chile, Colombia, Mexico, Peru, Venezuela, Guatemala, and Spain were typed by using M13 polymerase chain reaction-fingerprinting and orotidine monophosphate pyrophosphorylase (URA5) gene restriction fragment length polymorphism analysis with HhaI and Sau96I in a double digest. Both techniques grouped all isolates into eight previously established molecular types. The majority of the isolates, 68.2% (n=232), were VNI (var. grubii, serotype A), which accords with the fact that this variety causes most human cryptococcal infections worldwide. A smaller proportion, 5.6% (n=19), were VNII (var. grubii, serotype A); 4.1% (n=14), VNIII (AD hybrid), with 9 isolates having a polymorphism in the URA5 gene; 1.8% (n=6), VNIV (var. neoformans, serotype D); 3.5% (n=12), VGI; 6.2% (n=21), VGII; 9.1% (n=31), VGIII, and 1.5% (n=5) VGIV, with all four VG types containing var. gatii serotypes B and C isolates.     

245例女性阴道假丝酵母菌病的真菌分布及耐药性分析

目的 探讨女性阴道假丝酵母菌病的真菌分布及耐药性,为临床治疗提供依据.方法 对临床从阴道分泌物中分离出的245株假丝酵母菌属采用科玛嘉假丝酵母菌显色培养基和YBC鉴定卡进行鉴定,并采用Rosco纸片扩散法对5种抗真菌药物进行药物敏感试验.结果 245株假丝酵母菌属中白色假丝酵母菌193株占78.8％、光滑假丝酵母菌33株占13.5％、热带假丝酵母菌10株占4.1％、克柔假丝酵母菌6株占2.5％、其他假丝酵母菌3株占1.2％;在5种抗真菌药物中,耐药率最高的是伊曲康唑为33.1％(x2=99.20,P＜0.05),氟康唑耐药率为27.8％、酮康唑为18.8％、两性霉素B为7.4％、5-氟胞嘧啶为4.9％.结论 女性阴道假丝酵母菌感染以白色假丝酵母菌为主,对抗真菌药物有不同程度耐药,临床应重视药敏试验,合理用药.     

Epidemiologic differences among serotypes of Cryptococcus neoformans.

In the USA, the most prevalent serotype of the fungus, Cryptococcus neoformans, was serotype A. The serotype constituted 203 of 272 isolates from infections and 85 of 89 isolates from the environment. Serotype B or C isolates were infrequent causes of infection, except in Southern California, and were infrequent causes of infecand were not isolated at all from environmental sources. In Southern California, the absence of serotypes B and C in 67 soil and pigeon dropping isolates was striking, considering that 25 of 49 isolates from infections were serotypes B or C. The site in nature where serotypes B and C exist is currently unknown but differs from that of serotypes A and D. Serotype D may be unusually prevalent in both environmental and patient isolates from Denmark and Italy. Of 24 isolates from those countries, 21 were serotype D.     

Streptococcus pneumoniae serotype 15B polysaccharide conjugate elicits a cross-functional immune response against serotype 15C but not 15A

Protection conferred by pneumococcal polysaccharide conjugate vaccines (PCVs) is associated with PCV-induced antibodies against vaccine-covered serotypes that exhibit functional opsonophagocytic activity (OPA). Structural similarity between capsular polysaccharides of closely related serotypes may result in induction of cross-reactive antibodies with or without a cross-functional activity against a serotype not covered by a PCV, with the former providing an additional protective clinical benefit. Serotypes 15B, 15A, and 15C, in the serogroup 15, are among the most prevalent Streptococcus pneumoniae serotypes associated with invasive pneumococcal disease following the implementation of a 13-valent PCV; in addition, 15B contributes significantly to acute otitis media. Serological discrimination between closely related serotypes such as 15B and 15C is complicated; here, we implemented an algorithm to quickly differentiate 15B from its closely related serotypes 15C and 15A directly from whole-genome sequencing data. In addition, molecular dynamics simulations of serotypes 15A, 15B, and 15C polysaccharides demonstrated that while 15B and 15C polysaccharides assume rigid branched conformation, 15A polysaccharide assumes a flexible linear conformation. A serotype 15B conjugate, included in a 20-valent PCV (PCV20), induced cross-functional OPA serum antibody responses against the structurally similar serotype 15C but not against serotype 15A, both not included in PCV20. In PCV20-vaccinated adults (18–49 years), robust OPA antibody titers were detected against both serotypes 15B (the geometric mean titer [GMT] of 19,334) and 15C (GMTs of 1692 and 2747 for strains PFE344340 and PFE1160, respectively), but were negligible against serotype 15A (GMTs of 10 and 30 for strains PFE593551 and PFE647449, respectively). Cross-functional 15B/C responses were also confirmed using sera from a larger group of older adults (60–64 years).     

Penetratin and derivatives acting as antifungal agents

The synthesis, in vitro evaluation, and conformational study of RQIKIWFQNRRMKWKK-NH(2) (penetratin) and related derivatives acting as antifungal agents are reported. Penetratin and some of its derivatives displayed antifungal activity against the human opportunistic pathogenic standardized ATCC strains Candida albicans and Cryptococcus neoformans as well as clinical isolates of C. neoformans. Among the compounds tested, penetratin along with the nonapeptide RKWRRKWKK-NH(2) and the tetrapeptide RQKK-NH(2) exhibited significant antifungal activities against the Cryptococcus species. A comprehensive conformational analysis on the peptides reported here using three different approaches, molecular mechanics, simulated annealing and molecular dynamics simulations, was carried out. The experimental and theoretical results allow us to identify a topographical template which may provide a guide for the design of new compounds with antifungal characteristics against C. neoformans.     

The 13-valent pneumococcal conjugate vaccine (PCV13) elicits cross-functional opsonophagocytic killing responses in humans to Streptococcus pneumoniae serotypes 6C and 7A

The introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 dramatically reduced the incidence of invasive pneumococcal disease (IPD) caused by the seven serotypes covered by the vaccine. Following the introduction of PCV7, which contains a serotype 6B conjugate, some decrease in IPD due to serotype 6A was noted suggesting that the serotype 6B conjugate provided some partial cross-protection against serotype 6A. However, no effect on serotype 6C was observed. In 2010, a pneumococcal conjugate vaccine with expanded serotype coverage (PCV13) was introduced that expanded the serotype coverage to 13 serotypes including serotype 6A. To assess whether the 6A conjugate in PCV13 could potentially induce functional anti-6C antibody responses, an opsonophagocytic assay (OPA) for serotype 6C was developed. Randomly chosen subsets of immune sera collected from infants receiving three doses of PCV7 or PCV13 were tested in OPA assays for serotype 6A, 6B and 6C. PCV7 immune sera demonstrated strong OPA responses, defined as percentage of subjects having an OPA titer ≥1:8, to serotype 6B (100% responders), partial responses to serotype 6A (70% responders) but only minimal responses to serotype 6C (22% responders). In contrast, PCV13 immune sera showed strong OPA responses to serotypes 6A (100% responders), 6B (100% responders) and 6C (96% responders). Furthermore, during pre-clinical work it was observed that serotype 7F (included in PCV13) and serotype 7A (not included in PCV13) shared serogroup-specific epitopes. To determine whether such epitopes also may be eliciting cross-functional antibody, PCV13 immune sera were also tested in serotype 7A and 7F OPA assays. All PCV13 immune sera demonstrated OPA responses to both of these serotypes. Taken together these results suggest that immunization with PCV13 has the potential to induce cross-protective responses to related serotypes not directly covered by the vaccine.     

医院内深部真菌感染的临床分布和药敏结果

目的对350株临床深部真菌感染的标本进行分离鉴定和药敏试验,了解患者真菌性医院感染现状,为临床感染性疾病提供病原学诊断和合理使用抗真菌药物的依据。方法按常规方法培养,采用念珠菌显色培养基进行鉴定,对于少见的念珠菌采用PCR技术鉴定;对真菌用棉蓝染色直接镜检和培养相结合的方法进行鉴定。采用纸片扩散法进行药敏试验。结果350株真菌标本中,念珠菌属329株,占94.00%;真菌(丝状菌)21株,占6.00%;分离菌株对药物的敏感性分别为氟康唑92.40%、两性霉素B 97.57%、伊曲康唑93.01%、5-氟胞嘧啶88.10%。结论院内真菌感染以念珠菌属最为多见,特别是白色念珠菌和热带念珠菌;药敏结果显示氟康唑、两性霉素B、伊曲康唑、氟胞嘧啶均有较高的抗菌活性,但氟康唑对克柔念珠菌和光滑念珠菌有较高的耐药性;对送检标本及时进行真菌培养和药敏实验,合理使用抗真菌药物,减少多重耐药和深部真菌感染的发生。     

Application of ribotyping and IS200 fingerprinting to distinguish the five Salmonella serotype O6,7:c:1,5 groups: Choleraesuis sensu stricto, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C, and Typhisuis.

Sixty-seven strains of the five described Salmonella serotypes having antigens 6,7:c:1,5, that is S. enterica serotype Choleraesuis sensu stricto, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C, and Typhisuis, were examined for 16S rrn profile ribotype, presence of IS200 and phenotypic characters, including rate of change of flagellar-antigen phase and nutritional character. Choleraesuis sensu stricto and its Kunzendorf variant had related but distinct ribotypes. Therefore, ribotyping appears to be a suitable method for differentiating Choleraesuis non-Kunzendorf from Choleraesuis var. Kunzendorf. Some strains of Paratyphi C had 16S profiles that resembled that of Choleraesuis non-Kunzendorf, while others resembled that of Choleraesuis var. Kunzendorf. The Typhisuis profiles were like those of Choleraesuis non-Kunzendorf, while the Choleraesuis var. Decatur profiles were unlike those of any of the other four groups. Furthermore, IS200 fingerprinting discriminated between Choleraesuis var. Decatur and the other strains with antigenic formula O6,7:c:1,5, and comparison of IS200 patterns showed a high degree of genetic divergence within Choleraesuis var. Decatur. Our findings show that ribotyping and IS200 fingerprinting, combined with classical microbiological methods, distinguish the groups Choleraesuis non-Kunzendorf, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C and Typhisuis.     

阴道分泌物中白假丝酵母菌蛋白酶的致病性和耐药性研究

目的:检测阴道分泌物(白带)中白假丝酵母菌对人体的致病性,探讨其对抗真菌药物的敏感性。方法:采用沙堡葡萄糖琼脂平板法对阴道分泌物标本中分离的218株白假丝酵母菌进行蛋白酶活力测定。然后用Rosco纸片扩散法检测218株白假丝酵母菌对伊曲康唑、氟胞嘧啶、二性霉素B、酮康唑、氟康唑、制霉菌素、益康唑、咪康唑等抗真菌药物的敏感性。结果:218株白假丝酵母菌全部检出蛋白酶,其中蛋白酶活力高的为177株,占81.20%;活力中等的为32株,占14.68%;活力低的为9株,占4.13%。患者组蛋白酶阳性菌株的检出率及其蛋白酶的活力均显著高于携带者组(P<0.01)。白假丝酵母菌对制霉菌素、二性霉素B和氟胞嘧啶的敏感率均较高,分别为95.00%、89.00%和84.50%;其次为酮康唑和伊曲康唑,其敏感率分别为30.70%和11.90%;益康唑、咪康唑和氟康唑的敏感率较低,分别为7.30%、5.00%和1.80%。结论:蛋白酶是白假丝酵母菌的重要毒力因子,蛋白酶活力可直接反映人体感染毒力强弱和致病程度的客观指标。白假丝酵母菌对抗真菌药物易产生耐药性。因此开展对白假丝酵母菌的鉴定及药物敏感性检测,为指导临床抗感染治疗和合理选择药物,有效控制和减少真菌感染而奠定理论基础。     

Changes in Capsule and Drug Resistance of Pneumococci after Introduction of PCV7, Japan, 2010–2013

We aimed to clarify changes in serotypes and genotypes mediating β-lactam and macrolide resistance in Streptococcus pneumoniae isolates from Japanese children who had invasive pneumococcal disease (IPD) after the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into Japan; 341 participating general hospitals conducted IPD surveillance during April 2010–March 2013. A total of 300 pneumococcal isolates were collected in 2010, 146 in 2011, and 156 in 2012. The proportion of vaccine serotypes in infectious isolates decreased from 73.3% to 54.8% to 14.7% during the 3 years. Among vaccine serotype strains, genotypic penicillin-resistant S. pneumoniae strains also declined each year. Among nonvaccine serotype strains, 19A, 15A, 15B, 15C, and 24 increased in 2012. Increases were noted especially in genotypic penicillin-resistant S. pneumoniae isolates of serotypes 15A and 35B, as well as macrolide resistance mediated by the erm(B) gene in 15A, 15B, 15C, and 24.     

我国十省市空肠/结肠弯曲菌的生物型和血清型分布

本文采用Lior法对我国十省市不同来源的301株空肠/结肠弯曲菌进行了生物学分型与血清学分型研究。研究结果表明弯曲菌的生物型分布无明显地区差异,血清学总分型率为86.71%,共分出41个血清型。人源菌与鸡、猪。鸭源菌的血清型分布关系密切,其最常见的5个血清型中均包括LIO46、45和8。建立了3种新血清型LION-1、N-2和N-3。同一宿主可以同时感染2种血清型的弯曲菌。生物型和血清型分布之间未见特殊联系。     

Synthesis and investigation of antimicrobial activity of some bisbenzimidazole-derived chelating agents

The 1,2-bis(2-benzimidazyl)-1,2-ethanediol (1), 1,4-bis(2-benzimidazyl)-1,2,3,4-butanetetraol (2), 1,3-bis(2-benzimidazyl)-2-thiapropane (3), 1,3-bis(2-benzimidazyl)-2-thia-propane-dihydrochloride (4), 1,5-bis(2-benzimidazyl)-3-thiapentane (5), and 1,5-bis(2-benzimidazyl)-3-thiapentane dihydrochloride (6) chelating ligands are synthesised and characterised by using analytical data and modem spectroscopic methods such as FT-Raman, FT-IR, 1H- and 13C-NMR spectrometers. Their antimicrobial activities are reported by comparing the in vitro activities, with those of ofloxacin, ciprofloxacin, piperacillin, ampicillin and cefazolin antibacterial agents against fresh clinical isolates. Antifungal activities are reported on Candida albicans, Candida utilis, Cryptococcus neoformans fungi, and the results are referenced with amphotericin-B, fluconazole and flucytosine antifungal agents. It has been found that all the compounds have broad spectra activity and was either more active or equipotent to those compared antibiotic and antifungal agents.     

Studies on the heat resistance of Bacillus cereus spores and growth of the organism in boiled rice.

A comparison was made of the heat resistance of Bacillus cereus spores at 95 degrees C. Spores of serotype 1 strains were more resistant than those of the other types tested. However, there was little difference in the growth rate of the various serotypes in boiled rice at 22 degrees C. Most samples of uncooked rice contained multiple serotypes of B. cereus. These results indicate that the cooking procedure used for the preparation of cooked rice is likely to be selective for certain serotypes, and this is the most likely reason why type 1 is the most common serotype implicated in outbreaks of food poisoning and can be isolated from many routine samples of cooked rice.     

The ecology of Cryptococcus neoformans

Environmental isolations have established that Cryptococcus neoformans var. gattii serotype B appears to have a specific ecological association with Eucalyptus camaldulensis. The global distribution of the tree appears to correspond to the epidemiologic distribution of cryptococcosis caused by C. neoformans var. gattii. The epidemiology of cryptococcosis can primarily be explained by exposure to an infective aerosolized inoculum, such as basidiospores released from specific host plants and/or desiccated blastoconidia (yeast cells) disseminated from accumulations of dried pigeon dung. The ecology of C. neoformans still remains largely unresolved, studies on the host-parasite interaction between serotype B and E. camaldulensis are still in progress, and extensive environmental searches are now underway to determine the natural habitats of serotypes A, C and D.     

造血系统恶性疾病并发真菌败血症临床分析

目的 探讨造血系统恶性疾病并发真菌败血症的防治措施。方法 回顾性分析近6年来18例造血系统恶性疾病并发真菌败血症患者的临床情况。结果 真菌败血症占血液系统医院感染的3．7％，热带念珠菌是主要菌种，占72．2％，病死率达38．9％，真菌败血症的发生与原发病、强烈化疗、大剂量免疫抑制剂及抗生素长期反复应用有关；氟康唑、两性霉素B 5—氟胞嘧啶治疗有效率分别为14．3％、63．6％。结论 非白色念珠菌败血症有增多之势，尽早明确诊断、及时防治是关键，治疗首选两性霉素B 5—氟胞嘧啶。     

Distinct yearly change of serotype distribution of human rotavirus in Thailand as determined by ELISA and PCR.

A total of 241 group A rotavirus-positive stool samples collected from diarrhoeic patients in Thailand between July 1988 and June 1991 were characterized for their serotypes by enzyme-linked immunosorbent assay (ELISA) using serotype-specific monoclonal antibodies and by a polymerase chain reaction (PCR). In July 1988-June 1989, serotype 1 was the most prevalent (63.4%), followed by serotype 4 (11.0%) and serotype 2 (8.5%). In July 1989-June 1990, 59.8% were serotype 1, 24.3% were serotype 2, and 6.1% were serotype 3. In contrast, in July 1990-June 1991, serotype 3 was detected in the highest frequency (40.5%), 29.9% were serotype 1, and 27.3% were serotype 2. Thus, a distinct yearly change of serotype distribution of rotavirus in Thailand was observed in the three consecutive years. In particular, it was of note that the prevalence of serotype 3 greatly increased, in contrast to the previous studies in which almost no serotype 3 rotaviruses were detected in the years 1983-8 in Thailand.     

2017-2019年苏州地区儿童肺炎链球菌血清分型及耐药特征

  目的  了解苏州大学附属儿童医院呼吸道感染儿童肺炎链球菌菌株的血清型分布及耐药特征,为制定肺炎链球菌相关疾病的治疗和预防接种策略提供参考。  方法  采用乳胶凝集和荚膜肿胀试验对肺炎链球菌菌株进行血清分型,采用E-test法检测菌株对多种抗生素的耐药性。  结果  2017年1月-2019年7月共收集3 652株肺炎链球菌,主要来自于6月龄~2岁年龄段儿童,男女性别比为1.5:1。常见血清型为19F、6B、23F、19A及6A,13价肺炎球菌结合疫苗(13-valent pneumococcal conjugate vaccine, PCV13)的血清型覆盖率为73.1%(95% CI:71.6%~74.5%)。肺炎链球菌菌株对青霉素的耐药率为1.9%。青霉素不敏感肺炎链球菌(penicillin-non susceptible streptococcus pneumoniae, PNSP)(含中介和耐药菌株)对阿莫西林、红霉素、阿奇霉素等抗菌药物的耐药率高于青霉素敏感肺炎链球菌(penicillin-susceptible streptococcus pneumoniae, PSSP)菌株;PCV13疫苗血清型菌株的耐药率高于非疫苗血清型菌株。  结论  苏州地区儿童肺炎链球菌分离株PCV13疫苗血清型覆盖较高,且青霉素不敏感菌株大多为PCV13疫苗血清型。