Healthcare-associated infections in rheumatology in Japan

Prospective observational study was performed to elucidate the incidence and characteristics of healthcare-associated infections in a university hospital for rheumatology care. In this study, a total of 1,226 patients were prospectively enrolled between March 2004 and February 2006 and between April 2008 and December 2008. Healthcare-associated infection was defined as an infection developing after the third day of admission to the rheumatology ward. We detected the following 54 healthcare-associated infections in 49 patients: respiratory tract infection, 14 cases; Clostridium difficile infection, 2 cases; urinary tract infection, 4 cases; bloodstream infection, 9 cases; skin infection, 2 cases; reactivation of latent cytomegalovirus infection, 6 cases; herpes zoster infection, 5 cases; Candida infection, 7 cases; others, 4 cases. The incidence rate of respiratory tract infection was the highest. Methicillin-resistant Staphylococcus aureus was the causative bacterium in 21% of respiratory tract infections cases. Bloodstream infection due to the insertion of a catheter and opportunistic infection by a latent virus were also occurred commonly. Respiratory tract infection, bloodstream infection and opportunistic infection by a latent virus were the most common causes of healthcare-associated infection in rheumatology. It is important to pay more attention to healthcare-associated infection.     

Is malarial placental infection related to peripheral infection at any time of pregnancy?

Placental infection measured by placental smear at delivery is a standard indicator, widely used to characterize malaria infection in pregnant women. However, a single measure can hardly reflect the entire history of infection during pregnancy. To investigate the relation between this indicator and peripheral infection during pregnancy, we used data collected in a randomized trial of malaria prophylaxis in 928 pregnant women in Burkina Faso, 1987-1988, during which repeated measures of peripheral infection were taken. We analyzed placental infection using a logistic model, with two methods for handling missing data. Peripheral infection during two periods of pregnancy was significantly related to placental infection at delivery, before the fifth month: OR = 2.9 [1.3; 6.3]; after 7 months: OR = 4.9 [2.7; 8.8]). Therefore, an early peripheral infection may persist throughout gestation, and placental infection is a good indicator of the women's parasitological status during pregnancy.     

Chlamydia pneumoniae infection and Mycoplasma pneumoniae infection in pediatric patients

We evaluated a total of 1104 pediatric patients with acute lower respiratory tract infection for C. pneumoniae infection and M. pneumoniae infection by serology during July 1995 to December 1998. A microimmunofluorescence test was used for diagnosis of C. pneumoniae infection and a high density particle agglutination test for that of M. pneumoniae infection. Acute C. pneumoniae infection was found in 149 patients (13.5%), acute M. pneumoniae infection in 118 patients (10.7%), and dual infection in 27 patients (2.4%). Among 305 patients with pneumonia, M. pneumoniae infection (83 patients, 27.2%) was more common than C. pneumoniae infection (47 patients, 15.4%). However among 799 patients with bronchitis. C. pneumoniae infection (102 patients, 12.8%) was more common than M. pneumoniae infection (35 patients, 4.4%). Patients with C. pneumoniae infection were more younger and more frequently wheezing than patients with M. pneumoniae infection. These findings demonstrate that C. pneumoniae infection in very common pathogen of pediatric lower respiratory tract infection as M. pneumoniae infection in Japan.     

The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.     

Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection

Infections of T cells and natural killer (NK) cells play a central role in the pathogenesis of chronic active Epstein-Barr virus (CAEBV) infection. To characterize the virologic and cytokine profiles of T cell-type and NK cell-type infection, 39 patients with CAEBV infection were analyzed. Patients with T cell-type infection had higher titers of immunoglobulin G against early and late EBV antigens, suggesting lytic cycle infection. However, the pattern of EBV gene expression was latency type II; BZLF1, which is a hallmark of lytic cycle infection, could not be detected in any patients, regardless of infection type. Patients with CAEBV infection had high concentrations of proinflammatory, T helper cell type 1, and anti-inflammatory cytokines. The cytokine profile in patients with NK cell-type infection was similar to that in patients with T cell-type infection, but the concentration of IL-13 was high in patients with NK cell-type infection. These findings should help to clarify the pathogenesis of CAEBV infection and facilitate the development of more-effective treatments.     

青浦区人附红细胞体感染状况的调查

目的了解青浦区人群附红体的感染现状。方法以青浦区练塘、青浦镇和华新镇为调查区,随机抽取2个村/居委会,对一般人群(对照组),猪饲养员、猪肉屠宰和销售人员(密切接触组)进行问卷调查,镜检血涂片方法检查附红体的感染情况。结果共调查320人,查及感染者52人,总感染率为16.25%;其中密切接触组感染34人,对照组18人,感染率分别为21.25%和11.25%,感染率差异有统计学意义(χ2=4.243,P<0.05)。两组性别感染率差异无统计学意义(P>0.05)。密切接触组最低感染度为0.97%,最高感染度为40.73%,以轻度感染(占97.06%)为主,少数为中度感染(2.94%),未发现重度感染;对照组最低感染度为0.07%,最高感染度为38.47%,以轻度感染(占94.44%)为主,少数为中度感染(5.56%),无重度感染。结论上海市青浦区人群中存在附红细胞体的感染,以轻度感染为主。     

大鼠感染肺孢子菌模型诱导方法的优化

目的通过对实验条件的优化,建立一种高感染率和低死亡率的肺孢子菌感染模型诱导方法。方法以免疫抑制剂诱导大鼠自然感染肺孢子菌为基本方法,对比不同剂量、不同预处理方法、不同季节等因素对诱导大鼠肺孢子菌感染模型的成功率、感染度及动物死亡率等的影响。结果每鼠每次腹膜下注射2.5mg地塞米松(每周两次)至第8周,诱导的肺孢子菌感染率为87.50%,死亡率为0,3mg地塞米松组第7周诱导的肺孢子菌感染率为87.50%,死亡率为37.50%,2.0和3.5mg组感染率、死亡率分别为12.50%、0和75.00%、75.00%,差异有统计学意义(P<0.05);乙醚麻醉组肺孢子菌感染率为100%,非麻醉组为50.00%,差异有统计学意义(P<0.05);4~6月期间诱导的大鼠肺孢子菌感染率为62.50%,7~9月期间诱导的大鼠肺孢子菌感染率为100%,11月~次年1月组感染率为37.50%,差异有统计学意义(P<0.05)。结论地塞米松腹腔内注射诱导大鼠感染肺孢子菌,以每鼠每次2.5~3mg为最佳剂量;辅助乙醚吸入麻醉可提高肺孢子菌感染率;夏秋季节诱导的大鼠肺孢子菌感染率较高。     

新疆妇科就诊者高危型人乳头状瘤病毒与梅毒螺旋体感染的相关性研究

目的分析新疆乌鲁木齐市某医院妇科门诊就诊者高危型人类乳头状瘤病毒(HPV)感染与梅毒螺旋体(TP)之间的相关性。方法采用二代杂交捕获法对妇科门诊2 061名就诊者进行高危型HPV检测;采用ELISA(初筛)和梅毒螺旋体明胶颗粒凝集试验(确诊)对618例阳性者和979例非高危型HPV感染者进行梅毒螺旋体的血清学检查。结果 2 061名就诊者高危型HPV感染率为29.99%,年龄因素与高危型HPV感染率之间存在关联(r=0.168),以41～50岁年龄段高危型HPV阳性率最高;618例高危型HPV感染者TP阳性率10.68%,979例非高危型HPV感染者TP阳性率3.78%。高危型HPV感染者中,年龄因素和民族因素都与TP阳性率有相关性(r年龄=0.131,r民族=0.174),以41～50岁年龄段维吾尔族人群TP阳性率最高。结论本研究提供了新疆地区某医院妇科门诊就诊人群中高危型HPV和TP感染的流行病学数据。证明在妇科门诊就诊人群中高危型HPV感染与TP感染具有相关性。     

Viral evolution of hepatitis C in injection drug users

Injection drug users represent the largest cohort of patients with established hepatitis C virus (HCV) infection as well as the group that is at highest risk for new infections. Most published studies have focused on the clinical consequences of established HCV infection and have not examined the consequences of new infection. The aim of the current study was to measure the virological consequences of HCV in patients with ongoing injection drug use that might pose a risk for new and/or for superinfection with additional strains of HCV. We examined the following groups: (a) those with resolved HCV infection with ongoing injection drug use, (b) those with chronic infection who continued to inject and (c) those with chronic infection who no longer injected. Our study demonstrated a spectrum of responses. The majority of patients appeared to be 'protected' from new infection. None of six patients with resolved infection had detectable HCV RNA by quantitative or qualitative PCR when followed for 1 year. Similarly, despite ongoing injection drug use, no patient with persistent infection had a 'switch' in HCV genotype indicative of possible superinfection. Virological analysis of HCV quasispecies to detect possible infection with new variants of HCV in patients with apparently 'stable' infection, indicated divergence of virus over time, divergence that was unrelated to injection drug behaviour. Thus, patients with ongoing or prior HCV infection appear to develop immunity that protects against further infection with HCV despite repeated exposure.     

Differential antigenic hierarchy associated with spontaneous recovery from hepatitis C virus infection: implications for vaccine design

BACKGROUND: Cellular immune responses play a central role in the control of hepatitis C virus (HCV) infection, and in some individuals the adaptive immune response can spontaneously eradicate HCV infection. The development of vaccine candidates to prevent the spread of this infection remains a top priority; however, understanding the correlates of effective immunological containment is an important prerequisite. METHODS: Using 750 overlapping peptides, we directly characterized ex vivo total and subgenomic HCV-specific CD4(+) and CD8(+) T cell responses in a large cohort of participants with either chronic infection or spontaneously resolved infection. RESULTS: In chronic infection, the frequency of total CD4(+) T cells specific for HCV averaged 0.06%, compared with 0.38% in resolved infection. Total HCV-specific CD4(+) and CD8(+) T cell responses were strongly correlated in the setting of spontaneous resolution but not in the setting of viral persistence. NS3 protein-specific responses comprised a significantly greater proportion of the total response in resolved infection than in chronic infection, whereas responses to different regions comprised a larger proportion of responses in chronic infection. CONCLUSION: Because these data comprehensively define the breadth, specificity, and threshold of the T cell response associated with spontaneous recovery from HCV infection, they have important implications in the development of multigenic vaccine candidates for this common infection.     

Innate and acquired resistance to amebiasis in bangladeshi children

Entamoeba histolytica infection and colitis occurred in 55% and 4%, respectively, of a cohort of Bangladeshi preschool children observed for 2 years. DNA typing demonstrated that infecting E. histolytica isolates were genetically diverse. Innate resistance to infection in children was linked to the absence of serum anti-trophozoite IgG. Most children who lacked serum anti-trophozoite IgG failed to develop it in response to a new infection. The serum anti-trophozoite IgG response clustered in families, which is consistent with genetic inheritance. Acquired resistance to infection was linked to intestinal IgA against the carbohydrate-recognition domain of the E. histolytica galactose N-acetyl-d-galactosamine lectin. This was associated with an 86% reduction in new infection over 1 year. Amebiasis is a common and potentially serious infection in children from Dhaka, and both innate and acquired immune responses limit infection.     

Seasonal and spatial variation in natural densovirus infection in Anopheles minimus S.L. in Thailand

We report the first detection of a mosquito densovirus in anophelines, An. minimus species A and species C, and describe temporal and spatial variation in natural densovirus infection. A total of 814 (136 species A; 678 species C) adult mosquitos, obtained over a one year period from human biting catches at three locations in a village in western Thailand, were PCR tested for densovirus infection. Overall infection prevalence did not differ between species (15.4% species A; 14.5% species C). Infection prevalence showed significant seasonal variation. Some spatial heterogeneity in infection was also noted, with timing of peak infection prevalence varying between sites. PCR-screening of An. minimus s.l. larvae found an overall infection prevalence of 18.8%. Larval infection showed a significant positive association with rainfall recorded two months previous to larval collection. Infection in adult mosquitos showed a moderate relationship to environmental variables, but a significant negative correlation with larval infection in the previous month.     

Prenatal diagnosis of intrauterine infection with parvovirus B19 by the polymerase chain reaction technique.

Human parvovirus B19 is a recently recognized cause of fetal hydrops and death. Efforts to characterize the natural history of fetal infection with this virus have been hampered by the lack of sensitive and specific tests for diagnosis in utero. Using the highly sensitive polymerase chain reaction (PCR) assay, we determined the fetal infection status in 56 pregnancies by testing amniotic fluid, fetal serum, and maternal serum for B19 DNA and antibodies. Factors associated with a high risk of B19 infection were fetal disease, exposure to persons with erythema infectiosum, or signs or symptoms of acute B19 infection. Fifteen women (27%) were B19 IgM-positive, a status suggesting recent infection; the positivity of all of the corresponding fetal specimens for B19 DNA in the PCR was indicative of fetal infection. In four of these cases, serial ultrasonographic examinations documented spontaneous resolution of fetal hydrops. Twenty-four women (43%) were IgG-positive and IgM-negative; this pattern suggested prior infection. The PCR gave positive results, consistent with recent maternal infection, in four of these cases. Seventeen women (30%) were IgG-negative and IgM-negative, a pattern suggesting no prior infection; the PCR results in four cases were indicative of a possible early maternal infection or a possible atypical immune response. The PCR is a sensitive and rapid method for the diagnosis of intrauterine infection with human parvovirus B19 and promises to facilitate studies of the natural history and treatment of this infection.     

608例早孕绒毛宫内感染巨细胞病毒的免疫组织化学诊断

目的建立简便、快速的巨细胞病毒（ＣＭＶ）胚胎感染的诊断方法,早期诊断胚胎ＣＭＶ感染。方法应用免疫组化过氧化物酶抗过氧化物酶（ＰＡＰ）方法,检测与观察早孕绒毛组织的ＣＭＶ感染病灶。结果早孕绒毛６０８例,感染ＣＭＶ２２２例（３６．５％）。感染灶可分为三类,点状感染占７１％（１５８／２２２）,巢状感染占１７％（３７／２２２）,弥散状态感染占１２％（２７／２２２）。发现随胎龄增加巢状及弥散状感染增多,ＣＭＶ往往先侵入绒毛霍夫保尔细胞。经电镜观察验证了ＰＡＰ法。结论免疫组化ＰＡＰ法简便、灵敏、有效,可用于大量筛查宫内ＣＭＶ感染     

Serologically indicated pneumococcal respiratory infection in children.

Streptococcus pneumoniae infection was indicated serologically in 84 (19%) of 449 children hospitalized with middle or lower respiratory tract infection. Pneumococcal antigen was detected in acute serum in 28 patients, but in acute urine in only 2. An antibody response to type-specific capsular polysaccharides of S. pneumoniae was indicated in 27 patients and to a protein antigen, pneumolysin, in 25 patients, but to C-polysaccharide in only 10 patients. The observations mentioned above suggest that each serological test for pneumococcal etiology is insensitive, and to get an optimal result, a large panel of pneumococcal antigen and antibody assays must be used. Pneumococcal infection could be indicated serologically although no focus of infection, such as pneumonia or acute otitis media, or no laboratory evidence of bacterial infection as elevated values of C-reactive protein concentration, erythrocyte sedimentation rate or white blood cell count was present. Particularly antibody responses to pneumococcal pneumolysin were present in children without pneumonia or acute otitis media. Our results point out that no nonspecific parameter can be used for the selection of patients with probable pneumococcal etiology among children with respiratory tract infection. Concomitant viral infection, in most cases RSV infection, was present in a third of the children with pneumococcal infection. It is concluded that pneumococcal etiology should be actively sought for also in patients with viral respiratory infection, especially in young children with RSV infection.     

福建省钩虫病的流行现状

长期以来，福建省是以十二指肠钩虫为主的两种钩虫混合流行区。１９８０年以前，感染率在５０％左右，１９８０年以后，用全民服药的方法防治钩虫病，大部分地区的钩虫病感染率均呈下降趋势，但主要的感染场所亦由原来的甘薯地转为香蕉、芦笋等经济作物种植区。     

USP38 Inhibits Zika Virus Infection by Removing Envelope Protein Ubiquitination

Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South America has caused severe human congenital and neurologic disorders. Thus, it is vitally important to determine the inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to the ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost the ability to inhibit infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection.     

A view of dynamics of immune responses against tuberculosis infection through QFT

QFT has been approved as a diagnostic test of TB infection in April 2005 in Japan, and further adopted to health insurance in January 2006. QFT is now a necessary tool to diagnose TB infection, especially in contact investigation. Since QFT uses M. tuberculosis-specific antigens, which are absent from BCG and most of non-tuberculous mycobacteria, to stimulate blood samples, and Interferon-gamma (IFN-gamma) produced with antigen-specific T cells is measured to diagnose TB infection, QFT can specifically diagnose TB infection without influence of BCG vaccination or infection of most of non-tuberculous mycobacteria. There is another diagnostic test, T-SPOT.TB, which uses similar antigens to QFT, and these two tests are called as IGRAs (Interferon-Gamma Release Assays). However, as production of IFN-gamma is a small part of protective immune responses against TB infection, it is difficult from this point of view to understand the dynamics of protective immune responses against TB infection through IGRAs results. Especially, it is impossible to distinguish between active TB and latent TB infection, to identify time of TB infection, or to detect dormancy TB infection using current IGRAs. Using biomarkers other than IFN-gamma or antigens other than antigens used in current IGRAs, development of newer diagnostic tests which have these performances would be awaited.     

Neonatal chlamydial infection induces mixed T-cell responses that drive allergic airway disease

RATIONALE: Chlamydial lung infection has been associated with asthma in children and adults. However, how chlamydial infection influences the development of immune responses that promote asthma remains unknown. OBJECTIVES: To determine the effect of chlamydial infection at various ages on the development of allergic airway disease (AAD). METHODS: Mouse models of chlamydial lung infection and ovalbumin-induced AAD were established in neonatal and adult BALB/c mice. Neonatal or adult mice were given a chlamydial infection and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Features of AAD and inflammation were compared between uninfected or unsensitized controls. MEASUREMENTS AND MAIN RESULTS: Mild Chlamydia-induced lung disease was observed 10-15 days after infection, as evidenced by increased bacterial numbers and histopathology in the lung and a reduction in weight gain. After 6 weeks, infection and histopathology had resolved and the rate of weight gain had recovered. Neonatal but not adult infection resulted in significant decreases in interleukin-5 production from helper T cells and by the numbers of eosinophils recruited to the lung in response to ovalbumin exposure. Remarkably, the effects of early-life infection were associated with the generation of both type 1 and 2 ovalbumin-specific helper T-cell cytokine and antibody responses. Furthermore, although neonatal infection significantly attenuated eosinophilia, the generation of the mixed T-cell response exacerbated other hallmark features of asthma: mucus hypersecretion and airway hyperresponsiveness. Moreover, infection prolonged the expression of AAD and these effects were restricted to early-life infection. CONCLUSIONS: Early-life chlamydial infection induces a mixed type 1 and 2 T-cell response to antigen, which differentially affects the development of key features of AAD in the adult.