Simian varicella virus infection and reactivation in rhesus macaques trigger cytokine and Aß40/42 alterations in serum and cerebrospinal fluid.

Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aß42/Aß40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aß42/Aß40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aß42/Aß40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease.

Plasma levels of D-dimer and fibrin degradation products correlate with bullous pemphigoid severity: a cross-sectional study.

Bullous pemphigoid (BP), the most frequent blistering dermatosis in the elderly, is associated with increased mortality. The severity of BP can be assessed by detecting the anti-BP180 immunoglobulin G (IgG) concentration, but the lab test is not available in many community clinics. BP patients are usually in a hypercoagulable state with increased levels of D-dimer and fibrin degradation products (FDPs). We aimed to evaluate the use of D-dimer and FDPs in assessing BP severity. We compared the levels of plasma D-dimer, plasma FDPs, eosinophil counts, eosinophil cationic protein, and serum anti-BP180 IgG concentration between 48 typical BP patients and 33 Herpes zoster (HZ) patients (control group). Correlational analyses were conducted to determine the relationships between the lab values and common BP severity markers. The plasma D-dimer and FDP levels were higher in BP patients than in HZ controls (D-dimer: 3297 ± 2517 µg/L vs. 569.70 ± 412.40 µg/L; FDP: 9.74 ± 5.88 mg/L vs. 2.02 ± 1.69 mg/L, respectively, P < 0.0001). Significant positive correlations were found between D-dimer/FDP levels and BP severity markers (i.e. anti-BP180 IgG concentration [D-dimer: r = 0.3928, P = 0.0058; FDP: r = 0.4379, P = 0.0019] and eosinophil counts [D-dimer: r = 0.3625, P = 0.0013; FDP: r = 0.2880, P = 0.0472]) in BP patients. We also found an association between FDP and urticaria/erythema lesions (r = 0.3016, P = 0.0372), but no other BPDAI components. In 19 BP patients with complete remission after systemic glucocorticoid treatment, D-dimer and FDP levels decreased post-therapy (D-dimer: 5559 ± 7492 µg/L vs. 1738 ± 1478 µg/L; P < 0.0001; FDP: 11.20 ± 5.88 mg/L vs. 5.13 ± 3.44 mg/L; P = 0.0003), whereas they did not in BP patients with treatment resistant. Plasma D-dimer and FDP are convenient markers to evaluate BP severity assistant on BPDAI and eosinophil counts. FDP is also helpful for inflammatory lesions in BP patients.

Acute kidney injury and acyclovir-associated encephalopathy after administration of valacyclovir in an elderly person with normal renal function: A case report and literature review.

INTRODUCTION: Acyclovir (ACV)-associated encephalopathy is related to an increase in plasma levels of 9-carboxymethoxymethylguanine, an ACV metabolite, and is often reported in patients with renal dysfunction. We report a case of ACV-associated encephalopathy with rapid progression of renal dysfunction after oral administration of valacyclovir (VACV) and review literature of previous ACV-associated encephalopathy cases. PATIENT CONCERNS: An 88-year-old man was diagnosed with herpes zoster. VACV (3000 mg/day) treatment was initiated. Serum creatinine (Cr) level was 0.80 mg/dL. However, irritability, memory impairment, and decreased responsiveness occurred after 3 days. The Cr level was 6.76 mg/dL on admission. DIAGNOSIS: He was diagnosed with ACV-associated encephalopathy with acute kidney injury. INTERVENTIONS: VACV was discontinued, hemodialysis was initiated on the day of admission, and then the signs and symptoms improved approximately 72 hours after the admission. CONCLUSION: Worsening of renal function and encephalopathy should be a focus when using VACV or ACV, regardless of age and original renal function. Acute kidney injury and ACV-associated encephalopathy may particularly occur in the elderly even when renal function is normal. Therefore, regular monitoring of renal function and consciousness is necessary during VACV treatment.

Acute zoster plasma contains elevated amyloid, correlating with Aß42 and amylin levels, and is amyloidogenic.

Herpes zoster is associated with an increased dementia and neovascular macular degeneration risk and a decline in glycemic control in diabetes mellitus. Because amyloid is present and pathogenic in these diseases, we quantified amyloid, Aß40, Aß42, and amylin in 14 zoster and 10 control plasmas. Compared with controls, zoster plasma had significantly elevated amyloid that correlated with Aß42 and amylin levels and increased amyloid aggregation with addition of exogenous Aß42 or amylin. These results suggest that zoster plasma contains factor(s) that promotes aggregation of amyloidogenic peptides, potentially contributing to the toxic amyloid burden and explaining accelerated disease progression following zoster.

Correlation between Galectin-3 and Early Herpes Zoster Neuralgia and Postherpetic Neuralgia: A Retrospective Clinical Observation.

This study aims to explore the value of serum galectin-3 in patients with herpes zoster neuralgia (HZN) and postherpetic neuralgia (PHN) and other factors influencing HZN and PHN occurrence. Samples from forty patients with herpes zoster neuralgia (HZN) (Group H), 40 patients with nonherpes zoster neuralgia (Group N), and 20 cases of health check-up were collected. Patients were divided into PHN group (Group A) and non-PHN group (Group B) according to the occurrence of PHN in Group H. Galectin-3, T-lymphocyte subsets, and IL-6 were recorded in all patients. The changes of galectin-3 in patients with early HZN and PHN were analyzed by single-factor analysis and multifactor analysis. The age (P=0.012) and NRS scores (P < 0.001) of PHN patients were significantly higher than those of non-PHN patients and other neuralgia patients. The ratio of CD3+ (F = 80.336, P < 0.001), CD4+ (F = 12.459, P < 0.001) lymphocyte subsets, and CD4+/CD8+ (F = 15.311, P < 0.001) decreased significantly in PHN patients. The level of blood IL-6 (F = 139.446, P < 0.001) in PHN patients was significantly increased. Serum galectin-3 was significantly higher in HZN patients than in PHN patients (P < 0.05); IL-6 (OR = 10.002, 95% CI: 3.313-30.196, P < 0.001) and galectin-3 (OR = 3.719, 95% CI: 1.261-10.966, P=0.017) were the risk factors for HZN; galectin-3 (OR = 17.646, 95% CI: 2.795-111.428, P=0.002) was also the risk factor for PHN. ROC curve analysis also showed that serum galectin-3 was a better predictor of poor prognosis (AUC = 0.934, P < 0.001). Therefore, as an independent risk factor of HZN and PHN, serum galectin-3 may be used as a new biochemical marker in clinical practice.

Measurement of melatonin, indole-dioxygenase, IL-6, IL-18, ferritin, CRP, and total homocysteine levels during herpes zoster.

The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause a negative impact on the immune responses. The present study aimed to assess the levels of oxidative/inflammatory stress biomarkers in HZ patients compared with the controls. This case-control study included 43 HZ patients and 47 age-matched controls. Melatonin (MLT), Indole-dioxygenase (IDO), Interleukin-18 (IL-18), Interleukin-6 (IL-6), ferritin, C-reactive protein (hsCRP), and total homocysteine (tHcy) levels were measured and compared in both groups. The significant high levels of IDO, IL-18, IL-6, ferritin, hsCRP, and tHcy, as well as low levels of MLT were found in HZ patients compared with the controls (P < 0.001); these significant differences were also associated with rash and pain severity (P < 0.001). The final logistic regression model with the area under the curve (0.99; 95% confidence interval [CI], 0.98-1.00) showed the association of HZ with decreased level of MLT (odds ratio [OR], 0.95; 95% CI, 0.92-0.98; P = 0.007) and increased levels of tHcy (OR, 1.53; 95% CI, 1.06-2.19; P = 0.02). The findings showed increased inflammation-associated oxidative stress in HZ patients. Elevated tHcy levels and reduced MLT levels may be associated with the manifestation of HZ. More investigations are required to confirm the results.

Low level of hemoglobin A1c and the increased incidence of herpes zoster: longitudinal study.

Little is known about the association between glycemic status and herpes zoster. The aim of this study was to evaluate whether glycemic status, including both high and low hemoglobin A1c(HbA1c), is associated with subsequent herpes zoster. We conducted a retrospective longitudinal study in a large teaching hospital in Tokyo, Japan, from 2005 to 2016. We included all participants who underwent voluntary health check-ups at the hospital. Our primary outcome was the incidence of herpes zoster in groups of individuals stratified by HbA1c levels, which were compared using the generalized estimating equation (GEE), adjusting for participants' demographic characteristics, social history, body mass index, and comorbidities. A total of 81,466 participants were included in this study. The mean age (standard deviation) was 46.5 (12.1), and 39,643 (48.7%) participants were male. Among them, 1751 (2.1%) were diagnosed with diabetes prior to their first visits. After a median follow-up of 1784 [interquartile range (IQR), 749-3150] days, 673 (0.8%) participants developed herpes zoster. The incidence of herpes zoster was 1.45 per 1000 person-years. Compared with the reference group (HbA1c of 5.0-6.4%), the lowest HbA1c group (HbA1c of < 5.0%) had a significantly higher adjusted odds ratio (OR) (OR 1.63; 95% confidence interval (CI), 1.07-2.48) of developing herpes zoster. The group with an HbA1c of ≥ 9.5% had a higher but nonsignificant OR than the reference group (OR 2.15; 95% CI, 0.67-6.94). Our longitudinal study demonstrated that individuals in the lowest (< 5.0%) HbA1c group had a significantly higher risk of developing herpes zoster than the reference group (HbA1c of 5.0-6.4%) after adjusting for covariates.

Fatal disseminated visceral varicella zoster virus infection in a renal transplant recipient.

We report a case of fatal disseminated varicella zoster virus (VZV) with delayed-onset rash in a 66-year-old female more than 2 years following uncomplicated deceased donor renal transplantation. Whilst on a stable regimen of maintenance immunosuppression, the patient presented with chest and abdominal pain with concomitant hepatitis and pancreatitis. After pursuing multiple other potential causes of her symptoms, the correct diagnosis of VZV was only suspected after the development of a widespread vesicular rash-11 days after her initial symptoms. Despite antiviral therapy and inotropic support in the intensive care unit, the patient died. Simultaneous VZV hepatitis and pancreatitis in solid organ transplant recipients is uncommon. The new inactivated VZV vaccines have the potential to prevent post-transplant infections, with promising early clinical data on safety and efficacy in renal transplant recipients. VZV is an important preventable infection that should be considered in immunocompromised patients, even in the absence of rash.

Anti-varicella Zoster Virus IgG and hsCRP Levels Correlate with Progression of Coronary Artery Atherosclerosis.

The relationship between high levels of anti-Varicella Zoster Virus (VZV) IgG in cerebrospinal fluid (CSF) and cerebrovascular atherosclerosis commends a possible similar association in other vessels. We aimed to investigate the association of VZV-seropositivity with coronary artery atherosclerosis. We recruited 88 newly diagnosed patients with more than 50% stenosis in at least one of the main coronary arteries. As the control group, 99 age-matched individuals with normal/insignificant coronary artery findings were included. Clinical, paraclinical, and demographical data were gathered at the time of sampling. High-sensitivity C-reactive protein (hsCRP) levels were measured by nephelometry. VZV-seropositivity was determined by measuring of anti-VZV IgG level in plasma. Multivariable logistic regression was used to evaluate the correlation of data with coronary vascular atherosclerosis. The frequency of VZV-seropositivity was significantly higher in the atherosclerosis group compared to the controls (OR=1.88; 95%CI=1.03-3.44). The plasma levels of anti-VZV IgG were significantly higher in patients with atherosclerosis (Median=2.70, IQR=1.53-4.30 AU/mL) than in the controls (Median=2.10, IQR=1.70-3.10 AU/mL, p=0.034). The hsCRP levels in patients and controls were 5.19±2.00 and 1.51±1.07 mg/L, respectively. The correlation between hsCRP and anti-VZV IgG level in plasma was observed (r=0.40, p<0.001). The levels of hsCRP and anti-VZV IgG increased based on the number of diseased vessels but only the difference in hsCRP levels reached a significant level (p<0.001 and p=0.168, respectively). Our data suggest that VZV-seropositivity and hsCRP elevation jointly increase the risk of atherosclerosis. The multifactorial nature of atherosclerosis; however, leaves more options for the inflammatory milieu to be generated.

Simple and label-free pathogen enrichment via homobifunctional imidoesters using a microfluidic (SLIM) system for ultrasensitive pathogen detection in various clinical specimens.

Diseases caused by pathogenic microorganisms including bacteria and viruses can cause serious medical issues including death and result in huge economic losses. Despite the myriad of recent advances in the rapid and accurate detection of pathogens, large volume clinical samples with a low concentration of pathogens continue to present challenges for diagnosis and surveillance. We here report a simple and label-free approach via homobifunctional imidoesters (HIs) with a microfluidic platform (SLIM) to efficiently enrich and extract pathogens at low concentrations from clinical samples. The SLIM system consists of an assembled double microfluidic chip for streamlining large volume processing and HIs for capturing pathogens and isolating nucleic acids by both electrostatic and covalent interaction without a chaotropic detergent or bulky instruments. The SLIM system significantly increases the enrichment and extraction rate of pathogens (up to 80% at 10 CFU (colony forming unit) in a 1 mL volume within 50 min). We demonstrated its clinical utility in large sample volumes from 46 clinical specimens including environmental swabs, saliva, and blood plasma. The SLIM system showed higher sensitivity with these samples and could detect pathogens that were below the threshold of detection with other methods. Finally, by combining our SLIM approach with an isothermal optical sensor, pathogens could be detected at a very high sensitivity in blood plasma samples within 80 min via enrichment, extraction and detection steps. Our SLIM system thus provides a simple, reliable, cost-effective and ultrasensitive pathogen diagnosis platform for use with large volume clinical samples and would thus have significant utility for various infectious diseases.

Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster.

The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster.

Varicella-Zoster Virus DNA in Blood After Administration of Herpes Zoster Vaccine.

We studied the relationship between varicella-zoster virus (VZV) DNAemia and development of VZV-specific immunity after administration of live-attenuated zoster vaccine. VZV-DNAemia, detected by polymerase chain reaction (PCR), and VZV-specific effector (Teff) and memory (Tmem) T cells, was measured in 67 vaccinees. PCR was positive in 56% (9 direct, 28 nested) on day 1 and in 16% (1 direct, 10 nested) on day 14. Teff progressively increased in direct-PCR-positive vaccinees up to day 30, but Tmem did not. Conversely, Tmem, but not Teff, increased in direct-PCR-negative vaccinees on day 7. The kinetics of these immune responses and VZV DNAemia suggested that direct-PCR sample positive represented viremia.

Relationship between serum anti-varicella zoster virus antibody titer and time from onset of herpes zoster.

Herpes zoster is an internal reactivation of varicella zoster virus, and its onset depends on immunity against this virus. We have previously reported that antiviral antibody titers are inversely correlated with patient numbers. In this study, we hypothesized that patients with higher titers may be late visitors to the clinic, whose antibodies were already boosted at presentation because of the time lapse between onset of zoster and measurement of antibodies. We analyzed antibody titers of patients with acute herpes zoster who visited Fukuoka University Hospital from January 2009 to May 2016 (n = 141, 62 males and 79 females). Varicella zoster virus-specific immunoglobulin G, M and complement fixation tests were positive in 93.9%, 12.0% and 64.2% of the patients, respectively. Immunoglobulin G and complement fixation titers were strongly correlated (Spearman's r = 0.8634, P < 0.0001). Patients with high immunoglobulin G and complement fixation titers were immunoglobulin M-negative. Unexpectedly, immunoglobulin G and complement fixation titers showed large inter-subject variation, and were only weakly correlated with onset-measurement time lapse. Patients with consecutive tests tended to show increasing immunoglobulin G and complement fixation titers. Our data suggest that herpes zoster preferentially occurs in patients with low immunoglobulin G and complement fixation titers, and subsequently causes antibody elevation. However, the timing of elevation varies and can be as late as 10 days after zoster. The large variation in antibody titer over the time from onset to testing suggests that some mechanism exists that resists the local breakthrough of virus in the skin, and so delays the onset of blisters.

Influence of comorbidities on CD4+/CD8+ proportion in HIV-positive patients in Blumenau, State of Santa Catarina: a retrospective study.

INTRODUCTION: The objective was to identify comorbidities related to HIV-positive patients in Blumenau, State of Santa Catarina. METHODS: A retrospective, descriptive observational design study which analyzed data from 424 patients assisted by the sexually transmitted disease/acquired immunodeficiency syndrome (STD/AIDS) Specialized Care Service (SCS). RESULTS: Of 424 medical records analyzed, 388 patients presented CD4+/CD8+ ratios lower than 1. The most prevalent comorbidities were smoking, depression, alcoholism, and herpes zoster infection, in males and females. CONCLUSIONS: The most relevant comorbidity in both genders was herpes zoster, an important marker of immunity in patients. The lowest mean was observed among patients with neurotoxoplasmosis.

Decreased absolute numbers of CD3+ T cells and CD8+ T cells during aging in herpes zoster patients.

Herpes zoster (HZ) is an infectious dermatosis with high incidence worldwide. Age is a key risk factor for HZ, and postherpetic neuralgia (PHN) is the main sequelae. Until now, no index has been available to predict the pathogenesis of PHN, and rare reports have focused on the immune response during aging and PHN. In this study, we selected immunoglobulin and complement proteins as markers for humoral immunity, while T lymphocyte subsets and natural killer (NK) cells were selected as markers for cell immunity, to systematically study the characteristics of immune responses in the peripheral blood of HZ patients. Our data showed that the absolute number of CD3+ T cells and CD8+ T cells decreased during aging and PHN. This implies that more attention should be paid to prevent the occurrence of PHN, especially in the aged population.

Influence of comorbidities on CD4+/CD8+ proportion in HIV-positive patients in Blumenau, State of Santa Catarina: a retrospective study

Abstract INTRODUCTION: The objective was to identify comorbidities related to HIV-positive patients in Blumenau, State of Santa Catarina. METHODS: A retrospective, descriptive observational design study which analyzed data from 424 patients assisted by the sexually transmitted disease/acquired immunodeficiency syndrome (STD/AIDS) Specialized Care Service (SCS). RESULTS: Of 424 medical records analyzed, 388 patients presented CD4+/CD8+ ratios lower than 1. The most prevalent comorbidities were smoking, depression, alcoholism, and herpes zoster infection, in males and females. CONCLUSIONS: The most relevant comorbidity in both genders was herpes zoster, an important marker of immunity in patients. The lowest mean was observed among patients with neurotoxoplasmosis.

Comparing serum microRNA levels of acute herpes zoster patients with those of postherpetic neuralgia patients.

Postherpetic neuralgia (PHN) is commonly defined as pain persisting for at least 3 months after acute herpes zoster (AHZ) rash presentation. About one-tenth of all acute herpes zoster patients develop PHN. Circulating microRNAs (miRNAs) are promising biomarkers for infectious diseases; however, there has been no relationship established between circulating miRNAs and PHN to date; the aim of the present investigation was to elucidate this relationship.We compared serum levels of miRNA in PHN and AHZ patients. Twenty-nine patients with PHN and 37 patients with AHZ participated. MiRNA serum levels were determined via TaqMan Low Density Array (TLDA) and confirmed individually by RT-qPCR.TLDA results showed that the expression levels of 157 serum miRNAs in PHN patients were distinct from those in AHZ patients. Among these PHN patient serum miRNAs, 17 were upregulated and 139 were downregulated in contrast to those in AHZ patients. Receiver operational characteristic (ROC) curve analysis and RT-qPCR results altogether confirmed that the levels of miR-34c-5p, miR-107, miR-892b, miR-486-3p, and miR-127-5p were notably increased in PHN patients in comparison with those of AHZ patients. These miRNAs in circulation may regulate numerous relevant pathways. A few likely participate in the nervous system and inflammatory reactions.This study is the first to show that the expression profiles of numerous miRNAs vary in the PHN process. Among these, 5 types of serum miRNAs are very likely related to PHN development.

Brincidofovir treatment of acyclovir-resistant disseminated varicella zoster virus infection in an immunocompromised host.

Brincidofovir (BCV) is a broad-spectrum antiviral agent active in vitro against double-stranded DNA viruses including herpesviruses, adenoviruses, polyomaviruses, and poxviruses. We report successful BCV use in management of disseminated acyclovir- and cidofovir-resistant varicella zoster virus in an immunocompromised hematopoietic stem cell transplant patient with chronic graft-versus-host disease who was intolerant to foscarnet.

Varicella-zoster virus susceptibility and primary healthcare consultations in Norway.

BACKGROUND: Currently Norway does not recommend universal varicella vaccination for healthy children. This study assessed susceptibility to varicella-zoster virus (VZV) in the Norwegian population for the first time. METHODS: A national convenience sample of residual sera was tested for anti-VZV IgG by ELISA. We estimated age-specific seropositivity to VZV, controlling for sex and geographical distribution. We assessed differences between the proportions using the chi-square test and multivariable logistic regression. Seroprevalence data were compared to the varicella and herpes zoster-associated consultation rates in patients attending primary healthcare. RESULTS: Although 73.2 % (n = 1,540) of all samples were positive for VZV, only 11.2 % of samples collected from 1-year-olds were seropositive. There was a sharp increase in the proportion of seropositive in 3- and 5-year-olds (40.2 % and 65.4 %, respectively). By the school entry age of 6 years, 69.8 % of children were seropositive. The age-specific annual consultation rate for varicella in primary healthcare peaked in 1-year-olds, with 2,627 cases per 100,000 population. The profile of varicella-related consultations in primary healthcare mirrored the VZV seropositivity profile. The herpes zoster-related consultations in primary healthcare peaked in people over 70 years of age (702 cases per 100,000 population). CONCLUSIONS: VZV seroprevalence in Norway was somewhat lower than in some other European countries. The age-specific varicella-related consultation rates in primary healthcare mirrored the age profile of VZV seroprevalence.