Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load

BackgroundCrimean Congo hemorrhagic fever (CCHF) is a fatal disease with a mortality rate of 5–30%. CCHF can be asymptomatic or it may progress with bleeding and cause mortality.ObjectivesTo evaluate relation of viral load with mortality, clinical and laboratory findings in CCHF.Study designA total of 126 CCHF patients were included. Serum samples obtained from all patients on admission for measurement of viral load.ResultsIn our study, mortality rate was 11.1%. The most important prognostic factor was viral load. Mean viral load was 8.3 × 10⁷ copy/ml and 4.6 × 10⁹ copy/ml in survived and dead patients, respectively (p < 0.005). Probability of survival is found to be significantly reduced where AST >1130 U/l, ALT >490 U/l, CPK >505 U/l, LDH >980 U/l, platelet count <23 × 10³/l, creatinine >1.4 mg/dl, INR >1.3, d-dimer >7100 ng/dl, and viral load >1.03 × 10⁸ copy/ml. Patients with 10⁸ copy/ml or higher viral load had diarrhea, headache, unconsciousness, bleeding, and seizure significantly more frequently (p < 0.05). WBC, hemoglobin, platelet counts were significantly lower whereas AST, ALT, CPK, LDH, creatinine levels, PT and aPTT time, d-dimer levels, and INR were found to be significantly higher in these group.ConclusionsThere are several severity criteria for prognosis of CCHF. In addition to these parameters, we introduce creatinine as a predictive factor for prognosis. Our study, which has the largest number of patients among studies that evaluate viral load on CCHF shows that viral load is the most effective parameter on mortality.     

Correlation between viral load,multiplicity of infection,and persistence of HPV16 and HPV18 infection in a Dutch cohort of young women

BackgroundPersistent high-risk human papillomavirus infection precedes the development of cervical cancer. Here we evaluated the contribution of HPV16/18 viral load and the presence of infections with multiple HPV types to persistence and clearance of HPV16/18 infections.MethodsVaginal self-swabs were obtained from young women (16–29 y) with one year interval. HPV genotyping was performed using the highly sensitive SPF10-DEIA-LiPA₂₅ system. HPV16/18 DNA loads were quantified via an adapted, highly sensitive qPCR protocol targeting the L1 gene.ResultsWe identified 227 HPV16 and 111 HPV18 infections with follow-up. For HPV16 132/227 (58%) were persistent and 95/227 cleared. For HPV18 49/111 (44%) infections were persistent and 62/111 cleared. Baseline viral load was significantly higher in persistent infections than in clearing infections for both HPV16 (p = 0.022) and HPV18 (p = 0.013). At baseline, only HPV16 viral load was significantly higher in multiple HPV infections compared with single infections (p = 0.003). In logistic regression analysis HPV16 and HPV18 viral load were found to contribute to persistency with OR = 1.279 (95%CI = 1.074–1.524) and OR = 1.256 (95%CI = 1.028–1.533) per log-unit increase HPV16 and HPV18 viral load respectively. The presence of multiple HPV type infections was not associated with higher persistency.ConclusionHPV16/18 viral load might be used as a marker for persisting infections and is affected by the presence of multiple HPV infections. Evaluation of these parameters at the population level may be of value to assess the presence of persistent or clearing HPV16/18 infections as an early marker, and may provide useful quantitative information in (epidemiological) vaccine monitoring studies.     

Association of cytologic grade of anal “Pap” smears with viral loads of human papillomavirus types 16, 18, and 52 detected in the same specimens from men who have sex with men

BackgroundHuman papilloma virus (HPV) load has been linked to cellular abnormalities of the uterine cervix, and proposed as predictors of HPV persistence and progression of dysplasia to cervical cancer. However, the association of HPV viral load and anal dysplasia and cancer has not been as thoroughly investigated.ObjectivesTo examine the association of the viral loads of high-risk HPV types 16, 18, and 52, with the cytologic severity grading in anal-swab specimens of MSM with and without HIV-1 co-infection.Study designA cross-sectional study recruited 200 MSM in northern Thailand from July 2012 to January 2013. Real-time qPCR amplified portion of the HPV E6E7 gene, as well as the human β-globin gene to validate adequacy of the anal specimens and to normalize interpatient viral-load comparisons. Genotyping by linear-array assay identified and distinguished types 16, 18, and 52.ResultsHPV-16, and -18 viral loads increased with respect to the abnormality of the cytologic diagnoses (p < 0.05 for HPV-16, p < 0.01 for HPV-18). HIV-1 positivity was associated with higher HPV-18 viral load (p = 0.006). HPV-16 viral loads ≥10^2.24 copies per 5000 anal cells, and HPV-18 loads ≥10^3.15, were independently associated with abnormal cytology on logistic regression (p = 0.022, p = 0.041, respectively). Positive predictive values were 85.2% (23/27) and 80.0% (44/55) for the high viral load of a particular HPV-16 and the combined HPV-16, -18 and -52 types, respectively.ConclusionsHigh viral loads of HPV types 16 and 18 appear to be associated with anal cytologic abnormalities. The clinical utility of HPV viral loads to predict risk for anal cancer remains to be determined by a larger prospective cohort with sufficient frequency of high-grade dysplasia.     

Epstein-Barr virus (EBV) DNA levels in palatine tonsils and autologous serum from EBV carriers

A real-time polymerase chain reaction was employed to detect and quantitate Epstein-Barr virus (EBV) DNA in tonsils and autologous sera from EBV-seropositive children. EBV DNA was found in 95% of tonsils from 21 children and in 50% from 18 children with serum IgG titers to the virus capsid antigen (VCA) of > or =1:160 and 1:10 to 1:80, respectively (P = 0.002). Tonsils from children with titers > or =1:160 harbored more EBV DNA copies per mg tissue (mean, 1,237; range, < 2-13,998) than from children with titers 1:10 to 1:80 (mean, 23; range, < 2-226; P < 0.0001). By contrast, EBV DNA was detected only in serum from 25% of 20 children with titers > or = 1:160. Thus, ample differences in tonsillar EBV replication are mirrored inconstantly by detectable EBV in autologous serum suggesting that EBV DNA quantitation in tonsils may serve for refined monitoring of individuals at risk of EBV-associated lymphoproliferation.     

Hepatitis C virus infection in dialysis and chronic liver patients: Viraemia dependent anti-E2-antibody response

Cryptic hepatitis C virus (HCV) infection relates to patients infected chronically with HCV that are seronegative but have HCV-RNA. These patients are not identified by the standard serological tests for HCV, which are based on detection of antibodies to core, NS3 and NS5 antigens. They will, therefore, be wrongly diagnosed as non-infected, and are considered as a potential risk for others. Cryptic HCV infection in dialysis units occurs frequently and, due to medical procedures, is a major factor for contracting the virus when unrecognised. This study was conducted in order to assess the humoral immune responses to E2-antigen in sera of patients infected chronically with HCV. Recombinant E2 protein in enzyme linked immunosorbent assay (ELISA) and Western blot (WB) were used to test the occurrence of anti-E2 antibodies in the sera of patients from the liver clinic and of dialysis patients. The presence of E2 antibodies was found to be correlated with the presence of HCV-RNA and with viral load. Antibodies to the E2 protein could be detected in as many as 30% of the sera from dialysis patients with cryptic HCV infection (HCV-RNA only). The results suggest that detection of anti-E2 antibodies may enhance significantly HCV serological standard testing; especially among patients on dialysis, and that antibodies to envelope E2 protein appear to depend on and correlate with the presence of HCV particles.     

EB病毒抗体与DNA载量联合检测在儿童传染性单核细胞增多症中的诊断价值

目的 探讨EB病毒IgG、IgA和IgM抗体及DNA载量联合检测在儿童传染性单核细胞增多症中的诊断价值.方法 收集2012年1月至2015年3月间我院收治的170例儿童传染性单核细胞增多症患者作为观察组进行回顾性分析,另取130例健康体检儿童作为对照组,对其EB病毒抗体检测情况和DNA载量检测情况进行观察对比.结果 观察组患者EB-DNA阳性率及载量,VCA-IgG及VCA-IgM阳性率均明显高于对照组,差异有统计学意义(P＜0.05);两组儿童VCA-IgA阳性率比较差异无统计学意义(P＞0.05).3～6岁患儿人数最多,达到全部患儿的49.41％,且随年龄增长,EB-DNA阳性率及载量、VCA-IgG阳性率均有明显增高趋势,差异有统计学意义(P＜0.05),而VCA-IgA及VCA-IgM则无明显差异(P＞0.05).各单项检测中,VCA-IgM具有最佳的诊断价值,与其他指标相比差异有统计学意义(P＜0.05).采用VCA-IgM联合EB-DNA检测可有效提高灵敏度、特异度、准确度、阳性预测值及阴性预测值等各项指标,差异有统计学意义(P＜0.05).结论 EB病毒VCA-IgG、VCA-IgA和VCA-IgM三种抗体在对儿童传染性单核细胞增多症的诊断中,以IgM具有最佳的敏感度、特异度及阳性预测值,采用VCA-IgM联合EB病毒DNA载量检测对于儿童传染性单核细胞增多症有良好的诊断价值,值得临床推广应用.     

替比夫定联用阿德福韦酯在高病毒载量乙肝患者中的应用效果

目的 探讨替比夫定联用阿德福韦酯在HBeAg阳性高病毒载量乙肝患者的治疗效果和安全性.方法 采取简单随机抽样法选取我院肝病专科2014年2月-2015年2月80例HBeAg阳性高病毒载量乙肝患者作为研究对象,按照随机数表法随机分为对照组40例、观察组40例.对照组采用替比夫定治疗,观察组采用替比夫定联用阿德福韦酯治疗.观察两组患者治疗前和治疗3、6、12个月时的HBV DNA载量、HBeAg血清学转换、ALT复常及不良反应情况.结果 观察组6、12个月时的HBV DNA载量对数值比同期对照组降低程度更明显(P＜0.05).观察组治疗6、12个月时HBV DNA阴转率、HBeAg转阴率明显高于对照组.观察组治疗12个月时HBeAg转阴率、血清学转换率及ALT复常率较对照组明显提高.结论 替比夫定联用阿德福韦酯治疗高病毒载量乙肝患者具有较强抗病毒作用,对高病毒载量乙肝患者的临床治疗具有重要意义.     

Evidence for human immunodeficiency virus and Cryptococcus neoformans interactions in the pro-inflammatory and anti-inflammatory responses in blood during AIDS-associated cryptococcosis

Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, -8 and-10 and soluble TNF receptor II (sTNFR II) levels were measured at baseline, and after antifungal therapy for 2 weeks and 3 months, in plasma from 75 human immunodeficiency virus (HIV)-positive and 14 HIV-negative patients with cryptococcosis, and in plasma from 14 HIV-positive controls. At baseline, TNF-alpha, IL-6 and sTNFR II levels, and cryptococcal antigen titres, were increased in patients with fungaemia compared to controls (p < 0.02). The mediator levels were not influenced by the severity of the disease or subsequent death, but sTNFR II and IL-10 levels were reduced, together with virus load, in patients receiving anti-retroviral agents (p < 0.01). During antifungal therapy, sTNFR II levels decreased (p 0.003) in parallel with the virus load and with an increase in CD4 T-cell numbers.     

Biomechanics of the knee joint in flexion under various quadriceps forces

Bioemchanics of the entire knee joint including tibiofemoral and patellofemoral joints were investigated at different flexion angles (0° to 90°) and quadriceps forces (3, 137, and 411 N). In particular, the effect of changes in location and magnitude of restraining force that counterbalances the isometric extensor moment on predictions was investigated. The model consisted of three bony structures and their articular cartilage layers, menisci, principal ligaments, patellar tendon, and quadriceps muscle. Quadriceps forces significantly increased the anterior cruciate ligament, patellar tendon, and contact forces/areas as well as the joint resistant moment. Joint flexion, however, substantially diminished them all with the exception of the patellofemoral contact force/area that markedly increased in flexion. When resisting extensor moment by a force applied on the tibia, the force in cruciate ligaments and tibial translation significantly altered as a function of magnitude and location of the restraining force. Quadriceps activation generated large ACL forces at full extension suggesting that post ACL reconstruction exercises should avoid large quadriceps exertions at near full extension angles. In isometric extension exercises against a force on the tibia, larger restraining force and its more proximal location to the joint substantially decreased forces in the anterior cruciate ligament at small flexion angles whereas they significantly increased forces in the posterior cruciate ligament at larger flexion angles.     

Transcranial magnetic stimulation in the visual system. II. Characterization of induced phosphenes and scotomas

Transcranial magnetic stimulation (TMS) induces phosphenes and disrupts visual perception when applied over the occipital pole. Both the underlying mechanisms and the brain structures involved are still unclear. In the first part of this study we show that the masking effect of TMS differs to masking by light in terms of the psychometric function. Here we investigate the emergence of phosphenes in relation to perimetric measurements. The coil positions were measured with a stereotactic positioning device, and stimulation sites were characterized in four subjects on the basis of individual retinotopic maps measured by with functional magnetic resonance imaging. Phosphene thresholds were found to lie a factor of 0.59 below the stimulation intensities required to induce visual masking. They covered the segments in the visual field where visual suppression occurred with higher stimulation intensity. Both phosphenes and transient scotomas were found in the lower visual field in the quadrant contralateral to the stimulated hemisphere. They could be evoked from a large area over the occipital pole. Phosphene contours and texture remained quite stable with different coil positions over one hemisphere and did not change with the retinotopy of the different visual areas on which the coil was focused. They cannot be related exclusively to a certain functionally defined visual area. It is most likely that both the optic radiation close to its termination in the dorsal parts of V1 and back-projecting fibers from V2 and V3 back to V1 generate phosphenes and scotomas.