Penicillium marneffei Infection: An Emerging Disease in Mainland China

Penicillium marneffei is an emerging pathogenic fungus that can cause a life-threatening systemic mycosis in immunocompromised hosts, especially in patients with AIDS. This infection is endemic in Southeast Asia. With the prevalence of AIDS in this area, the number of patients with systemic penicilliosis marneffei is found to be increasing rapidly in mainland China in recent years. We recently reviewed 668 cases of penicilliosis marneffei in mainland China from January 1984 to December 2009 in cnki, cqvip, CBMdisc and PubMed. We analyzed epidemiological and clinical features, laboratory findings, reaction to therapy and prognosis of the disease. We found that 99.4 % of the cases were reported in the southern part of China; among these cases, 42.8 % were from Guangxi (286 cases) and 40.6 % were from Guangdong province (271 cases). Five hundred and eighty-six cases (87.7 %) of penicilliosis marneffei were reported with infection by the human immunodeficiency virus, 25 cases (3.8 %) with other immunocompromised diseases, and 57 cases (8.5 %) without any documented underlying diseases. Fever, weight loss, anemia, lymphadenopathy, hepatosplenomegaly, respiratory signs and skin lesions were the common clinical manifestations of P. marneffei infections. The 569 cases received antifungal therapy with a mortality of 24.3 % (138 cases), 99 cases who had not received antifungal therapy had a mortality of 50.6 %. P. marneffei was an emerging pathogenic fungus and become a medical and public health importance in mainland China. The immunocompromised patients should pay more attention to P. marneffei infection in the endemic areas.     

Nitrimidazine Compared with Metronidazole in the Treatment of Vaginal Trichomoniasis

A new substituted nitroimidazole, nitrimidazine (Naxogin), is compared with the established drug, metronidazole (Flagyl), for the treatment of vaginal trichomoniasis in a randomized double-blind trial. Nitrimidazine cured 39 (68%) out of 57 patients and showed no undesirable effects other than nausea in one patient. Metronidazole cured 51 (89%) out of 57 patients and also caused nausea in one patient; this cure rate corresponds with that previously reported in other trials. In the recommended dosage nitrimidazine is inferior to metronidazole, but is sufficiently effective to be useful in cases of intolerance to metronidazole.     

Chronic Opisthorchis viverrini Infection and Associated Hepatobiliary Disease Is Associated with Iron Loaded M2-like Macrophages

Chronic Opisthorchis viverrini-induced hepatobiliary disease is associated with significant leukocyte infiltration, including activated macrophages; however, the polarization of infiltrating macrophages remains to be fully characterized. In this study, we characterized macrophage polarization and phenotype in chronic O. viverrini-induced hepatobiliary disease in humans and hamsters using gene expression and histochemical analysis. Chronic O. viverrini infection and associated hepatobiliary diseases were associated with iron loaded M2-like macrophages in both humans and hamsters. This study provides suggestive evidence that iron loaded M2-like macrophages promote hepatobiliary disease in chronic O. viverrini infection.     

Reduced Mucosal Associated Invariant T-Cells Are Associated with Increased Disease Severity and Pseudomonas aeruginosa Infection in Cystic Fibrosis

Background

Primary defects in host immune responses have been hypothesised to contribute towards an inability of subjects with cystic fibrosis (CF) to effectively clear pulmonary infections. Innate T-lymphocytes provide rapid pathogen-specific responses prior to the development of classical MHC class I and II restricted T-cell responses and are essential to the initial control of pulmonary infection. We aimed to examine the relationship between peripheral blood lymphocyte phenotype and clinical outcomes in adults with CF.

Methods

We studied 41 subjects with CF and 22, age matched, non-smoking healthy control subjects. Lymphocytes were extracted from peripheral blood samples and phenotyped by flow-cytometry. Lymphocyte phenotype was correlated with sputum microbiology and clinical parameters.

Results

In comparison to healthy control subjects, mucosal associated invariant T (MAIT)-lymphocytes were significantly reduced in the peripheral blood of subjects with CF (1.1% versus 2.0% of T-lymphocytes, P = 0.002). MAIT cell concentration was lowest in CF subjects infected with P. aeruginosa and in subjects receiving treatment for a pulmonary exacerbation. Furthermore a reduced MAIT cell concentration correlated with severity of lung disease.

Conclusion

Reduced numbers of MAIT cells in subjects with CF were associated with P. aeruginosa pulmonary infection, pulmonary exacerbations and more severe lung disease. These findings provide the impetus for future studies examining the utility of MAIT cells in immunotherapies and vaccine development. Longitudinal studies of MAIT cells as biomarkers of CF pulmonary infection are awaited.     

Free Glycogen in Vaginal Fluids Is Associated with Lactobacillus Colonization and Low Vaginal pH

Objective

Lactobacillus dominates the lower genital tract microbiota of many women, producing a low vaginal pH, and is important for healthy pregnancy outcomes and protection against several sexually transmitted pathogens. Yet, factors that promote Lactobacillus remain poorly understood. We hypothesized that the amount of free glycogen in the lumen of the lower genital tract is an important determinant of Lactobacillus colonization and a low vaginal pH.

Methods

Free glycogen in lavage samples was quantified. Pyrosequencing of the 16S rRNA gene was used to identify microbiota from 21 African American women collected over 8–11 years.

Results

Free glycogen levels varied greatly between women and even in the same woman. Samples with the highest free glycogen had a corresponding median genital pH that was significantly lower (pH 4.4) than those with low glycogen (pH 5.8; p<0.001). The fraction of the microbiota consisting of Lactobacillus was highest in samples with high glycogen versus those with low glycogen (median = 0.97 vs. 0.05, p<0.001). In multivariable analysis, having 1 vs. 0 male sexual partner in the past 6 months was negatively associated, while BMI ≥30 was positively associated with glycogen. High concentrations of glycogen corresponded to higher levels of L. crispatus and L. jensenii, but not L. iners.

Conclusion

These findings show that free glycogen in genital fluid is associated with a genital microbiota dominated by Lactobacillus, suggesting glycogen is important for maintaining genital health. Treatments aimed at increasing genital free glycogen might impact Lactobacillus colonization.     

Effects of a One Year Reusable Contraceptive Vaginal Ring on Vaginal Microflora and the Risk of Vaginal Infection: An Open-Label Prospective Evaluation

Background

A contraceptive vaginal ring (CVR) containing Nestorone® (NES) and ethinyl estradiol (EE) that is reusable for 1- year (13 cycles) is under development. This study assessed effects of this investigational CVR on the incidence of vaginal infections and change in vaginal microflora.

Methods

There were 120 women enrolled into a NES/EE CVR Phase III trial and a microbiology sub-study for up to 1- year of cyclic product use. Gynecological examinations were conducted at baseline, the first week of cycle 6 and last week of cycle 13 (or during early discontinuation visits). Vaginal swabs were obtained for wet mount microscopy, Gram stain and culture. The CVR was removed from the vagina at the last study visit and cultured. Semi-quantitative cultures for Lactobacillus, Gardnerella vaginalis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, anaerobic gram negative rods (GNRs), Candida albicans and other yeasts were performed on vaginal and CVR samples. Vaginal infections were documented throughout the study.

Results

Over 1- year of use, 3.3% of subjects were clinically diagnosed with bacterial vaginosis, 15.0% with vulvovaginal candidiasis, and 0.8% with trichomoniasis. The detection rate of these three infections did not change significantly from baseline to either Cycle 6 or 13. Nugent scores remained stable. H₂O₂-positive Lactobacillus dominated vaginal flora with a non-significant prevalence increase from 76.7% at baseline to 82.7% at cycle 6 and 90.2% at cycle 13, and a median concentration of 10⁷ colony forming units (cfu) per gram. Although anaerobic GNRs prevalence increased significantly, the median concentration decreased slightly (10⁴ to 10³cfu per gram). There were no significant changes in frequency or concentrations of other pathogens. High levels of agreement between vaginal and ring surface microbiota were observed.

Conclusion

Sustained use of the NES/EE CVR did not increase the risk of vaginal infection and was not disruptive to the vaginal ecosystem.

Trial Registration

ClinicalTrials.gov NCT00263341, NCT00455156     

支原体生殖道感染妇女阴道微生态改变对临床转归的影响及XGboost模型构建

摘要 目的：探讨支原体生殖道感染妇女阴道微生态改变对临床转归的影响,并构建XGboost模型。方法：选取2019年1月~2020年12月于我院妇科门诊确诊的支原体生殖道感染妇女186例。根据治疗后3个月的临床转归分为有效组145例和无效组41例。比较两组患者的临床资料、阴道微生态形态学指标和功能学指标、微生态类型。使用Cox比例风险回归森林图筛选影响支原体生殖道感染妇女临床转归的因素,利用筛选出的影响因素构建XGboost模型并对影响因素按重要度排序,ROC曲线分析XGboost模型对支原体生殖道感染妇女临床转归的预测效能,校准曲线评价XGboost模型的准确度,临床决策曲线评价XGboost模型的有效性。结果：两组患者的流产次数、学历、年龄、避孕方式、生产次数对比有差异（P<0.05）。与有效组相比,无效组患者阴道微生态形态学和功能学各指标异常发生率、阴道微生态失调率明显较高（P<0.05）,无效组的需氧型阴道炎（AV）、外阴阴道假丝酵母菌病（VVC）、细菌性阴道病（BV）、BV+VVC、滴虫性阴道炎（TV）、BV中间型+VVC的检出率均明显较高（P<0.05）,无效组正常微生态及菌群正常、功能下降所占人数比例均明显更低,差异均有统计学意义（P<0.05）。年龄<25岁、高中以下学历、流产次数>1次、生产产次≥3次以及阴道微生态失调是影响支原体生殖道感染转归的重要因素（P<0.05）。构建的XGboost模型具有较高的预测效能,准确度和有效性均较高。结论：年龄、学历、流产次数、生产次数以及阴道微生态失衡是影响支原体生殖道感染临床转归的重要因素,本研究构建的XGboost模型具有较好的预测效能。     

Cytomegalovirus Infection in Inflammatory Bowel Disease Is Not Associated with Worsening of Intestinal Inflammatory Activity

Background

Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus.

Aim

Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations.

Methods

Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient.

Results

Among the 400 eligible patients, 249 had Crohn''s disease, and 151 had ulcerative colitis. In the group of Crohn''s disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine)

Conclusion

The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV and inflammatory bowel disease activity.     

Cirrhosis,Liver Transplantation and HIV Infection Are Risk Factors Associated with Hepatitis E Virus Infection

Background

Acute and chronic hepatitis E have been associated with high mortality and development of cirrhosis, particularly in solid-organ recipients and patients infected by human immunodeficiency virus. However, data regarding the epidemiology of hepatitis E in special populations is still limited.

Aims

Investigate seroprevalence and possible factors associated with HEV infection in a large cohort of immunosuppressed patients.

Methods

Cross-sectional study testing IgG anti-HEV in serum samples from 1373 consecutive individuals: 332 liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non-transplanted patients with chronic liver disease, 238 HIV-infected patients and 200 healthy controls.

Results

IgG anti-HEV was detected in 3.5% controls, 3.7% kidney recipients, 7.4% liver transplant without cirrhosis and 32.1% patients who developed post-transplant cirrhosis (p<0.01). In patients with chronic liver disease, IgG anti-HEV was also statistically higher in those with liver cirrhosis (2% vs 17.5%, p<0.01). HIV-infected patients showed an IgG anti-HEV rate of 9.2%, higher than those patients without HIV infection (p<0.03). Multivariate analysis showed that the factors independently associated with anti-HEV detection were liver cirrhosis, liver transplantation and HIV infection (OR: 7.6, 3.1 and 2.4). HCV infection was a protective factor for HEV infection (OR: 0.4).

Conclusions

HEV seroprevalence was high in liver transplant recipients, particularly those with liver cirrhosis. The difference in anti-HEV prevalence between Liver and Kidney transplanted cases suggests an association with advanced liver disease. Further research is needed to ascertain whether cirrhosis is a predisposing factor for HEV infection or whether HEV infection may play a role in the pathogeneses of cirrhosis.     

Syndrome with Joint Manifestations in Association with Mycoplasma pneumoniae Infection

Three patients experienced a rheumatic-fever-like illness with painful limitation of joint movements. The illnesses were due to infection with Mycoplasma pneumoniae. Joint symptoms have not been previously described in cases of M. pneumoniae infection.     

Characterization of a Novel Population of Low-Density Granulocytes Associated with Disease Severity in HIV-1 Infection

The mechanisms resulting in progressive immune dysfunction during the chronic phase of HIV infection are not fully understood. We have previously shown that arginase, an enzyme with potent immunosuppressive properties, is increased in HIV seropositive (HIV+) patients with low CD4⁺ T cell counts. Here we show that the cells expressing arginase in peripheral blood mononuclear cells of HIV+ patients are low-density granulocytes (LDGs) and that whereas these cells have a similar morphology to normal-density granulocyte, they are phenotypically different. Importantly, our results reveal that increased frequencies of LDGs correlate with disease severity in HIV+ patients.     

Rash Associated with Coxsackie A9 Infection

Coxsackie A9 virus was identified by the authors during the fall of 1965 in Montreal in six children with fever and exanthem. Three of the six children were siblings. The exanthem was centrally distributed as described by Lerner et al. and consisted of discrete maculopapules 3 to 4 mm. in diameter. The viral agent was recovered and identified in tissue culture in five cases, while in the sixth Coxsackie type-A lesions were produced in suckling mice. Serological confirmation was obtained in two patients from whom sera were available. In contrast, no exanthem was observed in three older patients with a diagnosis of aseptic meningitis associated with Coxsackie A9 virus. In only one of 16 patients with Coxsackie B virus infection was an exanthem observed during the same period.The true incidence of Coxsackie A9-associated exanthems is difficult to determine because of the benign nature of the disease.     

Cholecystolithiasis Is Associated with Clonorchis sinensis Infection

Background

The objective of this study was to analyze gallbladder stones for direct evidence of a relationship between Clonorchis sinensis infection and gallbladder stones formation.

Methodology

We investigated one hundred eighty-three gallbladder stones for the presence of Clonorchis sinensis eggs using microscopy, and analyzed their composition using Fourier transform infrared spectroscopy. We confirmed the presence of Clonorchis sinensis eggs in the gallbladder stones using real-time fluorescent PCR and scanning electron microscopy.

Principal Findings

Clonorchis sinensis eggs were detected in 122 of 183 gallbladder stones based on morphologic characteristics and results from real-time fluorescent PCR. The proportion of pigment stones, cholesterol stones and mixed gallstones in the egg-positive stones was 79.5% (97/122), 3.3% (4/122) and 17.2% (21/122), respectively, while 29.5% (18/61), 31.1% (19/61) and 39.3% (24/61) in the egg-negative stones. The proportion of pigment stone in the Clonorchis sinensis egg-positive stones was higher than in egg-negative stones (P<0.0001). In the 30 egg-positive stones examined by scanning electron microscopy, dozens or even hundreds of Clonorchis sinensis eggs were visible (×400) showing a distinct morphology. Many eggs were wrapped with surrounding particles, and in some, muskmelon wrinkles was seen on the surface of the eggs. Also visible were pieces of texture shed from some of the eggs. Some eggs were depressed or without operculum while most eggs were adhered to or wrapped with amorphous particles or mucoid matter (×3000).

Conclusion

Clonorchis sinensis eggs were detected in the gallbladder stones which suggests an association between Clonorchis sinensis infection and gallbladder stones formation, especially pigment stones.     

Sporotrichosis: An Emerging Neglected Opportunistic Infection in HIV-Infected Patients in Rio de Janeiro,Brazil

Sporotrichosis associated with zoonotic transmission remains a relevant public health problem in Rio de Janeiro, Brazil, affecting a large at-risk population, which includes HIV-infected individuals. We assessed patients co-infected by Sporothrix spp. and HIV over time in the context of an unabated sporotrichosis epidemic.A retrospective cohort retrieved information from a National reference institute for infectious diseases regarding 48 patients with sporotrichosis-HIV co-infection (group 1) as well as 3,570 patients with sporotrichosis (group 2), from 1987 through March 2013. Most patients from group 1 were male (68.8%), whereas women were predominant in group 2 (69.1%; p<0.0001). Patients from group 1 were younger than those from group 2 (μ = 38.38±10.17 vs. 46.34±15.85; p<0.001) and differed from group 2 in terms of their race/ethnic background, with 70.8% non-white patients in group 1 vs. 38.6% from group 2 (p<0.0001). Close to half (∼44%) of the patients from group 1 were hospitalized due to sporotrichosis over time, whereas hospitalization was very unlikely in group 2, among whom approximately 1% were hospitalized over time. Dissemination of sporotrichosis was the main cause of hospitalization in both groups, although it was more common among hospitalized patients from group 1 (19/21 [90.5%] vs. 16/37 [43.2%]; p<0.001). Over the period under analysis, eight patients died due to sporotrichosis (3/48 vs. 5/3,570). The diagnosis of sporotrichosis elicited HIV testing and subsequent diagnosis in 19/48 patients, whereas 23/48 patients were simultaneously diagnosed with the two infections.HIV infection aggravates sporotrichosis, with a higher incidence of severe disseminated cases and a higher number of hospitalizations and deaths. Underserved populations, among whom sporotrichosis has been propagated, have been affected by different transmissible (e.g., HIV) and non-transmissible diseases. These populations should be targeted by community development programs and entitled to integrated management and care of their superimposed burdens.     

Neuroglobins,Pivotal Proteins Associated with Emerging Neural Systems and Precursors of Metazoan Globin Diversity

Neuroglobins, previously thought to be restricted to vertebrate neurons, were detected in the brain of a photosymbiotic acoel, Symsagittifera roscoffensis, and in neurosensory cells of the jellyfish Clytia hemisphaerica. For the neuroglobin of S. roscoffensis, a member of a lineage that originated either at the base of the bilateria or of the deuterostome clade, we report the ligand binding properties, crystal structure at 2.3 Å, and brain immunocytochemical pattern. We also describe in situ hybridizations of two neuroglobins specifically expressed in differentiating nematocytes (neurosensory cells) and in statocytes (ciliated mechanosensory cells) of C. hemisphaerica, a member of the early branching animal phylum cnidaria. In silico searches using these neuroglobins as queries revealed the presence of previously unidentified neuroglobin-like sequences in most metazoan lineages. Because neural systems are almost ubiquitous in metazoa, the constitutive expression of neuroglobin-like proteins strongly supports the notion of an intimate association of neuroglobins with the evolution of animal neural systems and hints at the preservation of a vitally important function. Neuroglobins were probably recruited in the first protoneurons in early metazoans from globin precursors. Neuroglobins were identified in choanoflagellates, sponges, and placozoans and were conserved during nervous system evolution. Because the origin of neuroglobins predates the other metazoan globins, it is likely that neuroglobin gene duplication followed by co-option and subfunctionalization led to the emergence of globin families in protostomes and deuterostomes (i.e. convergent evolution).