Blood Titers Research Articles

Investigation of persistent infection of bovine viral diarrhea virus (BVDV) in Holstein dairy cows.

The aim of this study was to investigate the persistent infection (PI) of bovine viral diarrhea virus (BVDV) along with its coexistence between BVDV antibody titer and BVD virus in blood of Holstein dairy cows. Only large commercial farms (each contained < 1000-3000 unvaccinated cows) were included. There were 11 dairy cattle herds. They included nearly 20,000 dairy cows. Totally, 140 cows, > 3months to almost 10years old, were randomly sampled. Indirect enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect BVDV antibody and virus, respectively. The percent positivity (PP) < 14 and ≥ 14 values are interpreted negative and positive, respectively. Simultaneously, whole blood samples pooled in groups of 10 animals were used for molecular detection of BVDV. The results revealed that 138 (98.56%) out of 140 cows were positive for BVDV antibody, while the BVDV antigen was detected only in 2 (1.42%) cows, which were negative for BVDV antibody and so were considered as persistent infection (PI) cows. They were also retested 3weeks apart. Since the results showed the strong coexistence between seropositivity and BVD virus, in the infected dairy cattle herds, the combination of simple ELISA and pooled whole blood RT-PCR strategy could be an achievable approach to detect PI animals.

The effectiveness of colostral antibodies for preventing bovine leukemia virus (BLV) infection in vitro

BackgroundBovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL). The incidence of EBL in Japan is increasing annually; and the cases of EBL in cattle younger than 2 years old has been reported. Therefore, it is vital to find a method to control BLV infection, especially in young calves. In this study, to evaluate the protective ability of colostral antibodies against BLV infection, as well as the potential for BLV infection mediated by colostrum/milk, we investigated temporal fluctuations in the anti-BLV antibody titer and BLV proviral load (PVL) in colostrum/milk and peripheral blood of six infected dams during lactation. The association between PVL and antibody titer in colostrum and peripheral blood was then investigated using samples from a further twenty-seven cattle. Antibody concentrations were measured with a Syncytium-induction Inhibition Assay using colostral/milk whey and serum. PVL in peripheral blood and colostrum was measured by real-time PCR.ResultsColostral antibodies showed high inhibitory activity until day 3 of lactation. The antibody titer and PVL in peripheral blood showed lesser changes than those in colostrum/milk throughout lactation. The colostral antibody titer was significantly higher than the serum antibody titer in all samples, whereas the colostrum PVL was significantly lower than the blood PVL. The blood PVL showed a significant correlation with serum antibody titer, colostrum PVL, and colostral antibody titer. However, there were no major correlations between the serum and colostral antibody titers.ConclusionsThis is the first report investigating the temporal changes in colostral antibody titer in terms of inhibiting BLV infection in vitro. The results of antibody detection by Syncytium-induction Inhibition Assay suggested that the protective activity of the colostral antibodies against BLV infection would be conferred by anti-BLV gp51 antibody. The high antibody titer of colostral whey suggests that colostral whey could be a potential source of antibodies with a low risk of infection in neonatal calves.

Experimental application of a split-conjugated vaccine against animal brucellosis in small cattle

A study was made of the blood samples of small cattle for brucellosis with various serological reactions when testing a split-conjugated vaccine against animal brucellosis three and a half, four and a half months and nine months after immunization. Positive reaction of small cattle to brucellosis in the complement fixation reaction and the agglutination reaction of 40.7% of sheep and goats, and 44.4% of animals in Ros-Bengal after 3.5 months of vaccination. The vaccine has a high immunogenicity against goats, a high enough antibody titer in blood three and a half months after vaccination, when tested with agglutination and Rose-Bengal, breakdown was detected in 83.3% of animals, and in the complement fixation reaction it was 66.7%, which will, in our opinion, effectively use this vaccine in the fight against goat brucellosis. Immunized sheep in the complement-fixation reaction and Rose-Bengal assay reacted positively only in 33.3% of cases. When the agglutination reaction was established three and a half months after the introduction of the vaccine - in 28.6% of the animals, in connection with the data obtained, we recommend looking for new immunoprotectors capable of enhancing the humoral immune response of sheep to the antigen of the tested anti-brucellosis vaccine. Nine months after the vaccination of the split-conjugated vaccine in all blood samples of small cattle (sheep and goats) with all of the above reactions, there was no positive test, which indicates the disappearance and complement-binding and agglutinating antibodies from the bloodstream of animals, and thus the opportunity is given differentiate postvaccinal antibodies in the blood serum of animals, from post-infection, in the case of their detection within the time specified above.

Impact of maternally derived pertussis antibody titers on infant whole-cell pertussis vaccine response in a low income setting

BackgroundMaternal vaccines against pertussis are not yet recommended in the developing world. Besides unclear burden estimates, another concern is that transplacental transfer of maternal pertussis antibodies could result in attenuation of the immune response to whole cell pertussis (DTwP) primary vaccination series in infants. This study was taken up to determine whether higher levels of maternal pertussis antibodies attenuate immune response of infants to DTwP vaccination series given at 6–10–14 weeks of age. MethodologyA total of 261 pregnant women and their infants from four low-income settlements in Karachi, Pakistan were enrolled in this study. The study endpoints were infant antibody titers for Pertussis toxin (PTx), Filamentous hemagglutinin antigen (FHA), Pertactin (PRN) and Fimbriae type 2/3 (FIM) – from birth through 18 weeks of age. Cord blood or pre-vaccine pertussis antibody titers indicate the concentration of maternal antibodies transferred to infants. Linear regression models were used to determine the association between higher maternal antibody titers and infant immune response to DTwP vaccine. Geometric Mean Ratio (GMR) was calculated as the ratio of infant antibody titers at specified time points against the maternal antibody titers at the time of delivery. ResultsAt eighteen weeks of age, the adjusted β regression coefficient for PTx was 0.06 (95% CI: -0.49-0.61), FHA 0.02 (95% CI: -0.26 -0.29), PRN 0.02 (95%CI -0.38- 0.43), and FIM 0.17 (95%CI: -0.21-0.54). Among infants who received at least two doses of DTwP vaccine, higher maternal antibody titers did not have any attenuating effect on infant post-immunization antibody titers against all four pertussis antigens. ConclusionMaternal pertussis antibodies did not attenuate infant’s immune response to pertussis antigens in DTwP primary vaccine given at 6–10–14 weeks of age.

Maternal transfer of anti HPV 6 and 11 antibodies upon immunization with the 9-valent HPV vaccine

ABSTRACTBackground: This exploratory analysis was conducted to characterize the level of HPV types 6/11 antibodies in peripartum maternal blood and in cord blood of infants born to women who received 9-valent HPV (9vHPV) vaccine or quadrivalent HPV (qHPV) vaccine in a pivotal efficacy study (V503-001, NCT 00543543).Methods: A total of 21 mother-infant pairs had evaluable HPV 6/11 results available for analysis. HPV6/11 antibodies were assessed using competitive Luminex immunoassay. The distribution of the ratios of infant to mother anti-HPV antibodies (i.e., infant-anti-HPV/mother- anti-HPV) was summarized.Results: All mothers and infants were seropositive to HPV 6 and HPV 11. Anti-HPV 6/11 geometric mean titers (GMTs) in peripartum maternal blood and in cord blood of infant born to study participants were highly correlated. A 100% of infants born to seropositive mothers were also seropositive. The GMT ratios of peripartum maternal blood vs. those in cord blood were HPV 6: 1.23 [0.43, 3.49] and HPV 11: 1.29 [0.54, 3.07] in the 9vHPV vaccine group and HPV 6: 1.33 [0.41, 4.29] and HPV 11: 1.19 [0.45, 3.13] in the qHPV vaccine group, respectively.Conclusions: These results indicate that antibodies induced by the 9vHPV vaccine cross the placenta, which could potentially be beneficial against HPV6/11 infection and related disease such as recurrent respiratory papillomatosis.

Blood CRP levels are elevated in children and adolescents with functional neurological symptom disorder.

There is accumulating evidence that patients with functional neurological symptom disorder (FND) show activation of multiple components of the stress system-the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and brain regions involved in arousal- and emotion-processing. This study aims to examine whether the immune-inflammatory component of the stress system is also activated. C-reactive protein (CRP) blood titre levels were measured in 79 children and adolescents with FND. CRP values ≥ 2mg/L suggest low-grade inflammation. CRP values > 10mg/L suggest a disease process. Sixty-six percent of subjects (n = 52) had CRP titres ≥ 2mg/L. The upward shift in the distribution of CRP levels suggested low-grade inflammation (median CRP concentration was 4.60mg/L, with 75th and 90th percentiles of 6.1 and 10.3mg/L, respectively). Elevated CRP titres were not explained by sex, pubertal status, BMI, or medical factors. Confounder analyses suggested that history of maltreatment (χ2 = 2.802, df = 1, p = 0.094, φ = 0.190; β = 2.823, p = 0.04) and a diagnosis of anxiety (χ2 = 2.731, df = 1, p = 0.098, φ = 0.187; β = 4.520, p = 0.061) contributed to elevated CRP levels. Future research will need to identify the origins and locations of immune cell activation and the pathways and systems contributing to their activation and modulation. Because functional activity in neurons and glial cells-the brain's innate effector immune cells-is tightly coupled, our finding of elevated CRP titres suggests activation of the immune-inflammatory component of the brain's stress system. A more direct examination of inflammation-related molecules in the brain will help clarify the role of immune-inflammatory processes in FND.

Microscopic polyangiitis presented with biopsy-confirmed pleuritis.

We describe a case of microscopic polyangiitis manifested as pleuritis confirmed by thoracoscopic biopsy. An 80-year-old man presented with a three-day history of shortness of breath and cough. Chest radiography revealed patchy opacities in the lower fields of the bilateral lung and right-sided pleural effusion. Thoracentesis revealed lymphocytic pleural exudates. Thoracoscopic biopsy specimens were compatible with fibrotic pleuritis. He developed rapidly progressive glomerulonephritis with elevated myeloperoxidase anti-neutrophil cytoplasmic antibody titer in blood and pleural effusion. Although the patient was resistant to two weekly courses of pulse steroid therapy, he was successfully treated with a five-day course of intravenous immunoglobulin.

Tolerogenic β2-glycoprotein I DNA vaccine and FK506 as an adjuvant attenuates experimental obstetric antiphospholipid syndrome

DNA vaccines have recently emerged as a therapeutic agent for treating autoimmune diseases, such as multiple sclerosis. Antiphospholipid antibody syndrome (APS) is an autoimmune disease characterized by β2-glycoprotein I (β2-GPI)-targeting antiphospholipid antibodies (APAs) and vascular thrombosis or obstetrical complications. To examine the therapeutic potential of a β2-GPI DNA vaccine, we administered a vaccine mixed with FK506 as an adjuvant to a mouse model of obstetric APS. First, the pCMV3-β2-GPI DNA vaccine, which encodes the full-length human β2-GPI gene, was constructed. Then, we administered the β2-GPI DNA vaccine in 0.1 ml of saline, mixed with or without 100 μg of FK506, intramuscularly to the mice on days 28, 35 and 42. Blood titers of the anti-β2-GPI antibody, platelet counts, activated partial thromboplastin times (aPTTs), and the percentage of fetal loss were measured. We also stimulated murine splenic T cells ex vivo with β2-GPI and determined the T helper cell proportion and cytokine secretion. The administration of the β2-GPI DNA vaccine mixed with FK506 reduced the blood IgG anti-β2-GPI antibody titers and suppressed APS manifestations in mice. The combination also suppressed interferon-γ and interleukin (IL)-17A secretion but increased the Treg cell proportion and IL-10 secretion in murine splenic T cells following ex vivo stimulation with β2-GPI. Our results demonstrated the therapeutic efficacy of a β2-GPI DNA vaccine and FK506 as an adjuvant in a murine model of obstetric APS. Possible mechanisms include the inhibition of Th1 and Th17 responses and the up-regulation of Treg cells.

Antibody response to Influenza booster vaccination in Franches-Montagnes stallions supplemented with Equi-Strath® : a randomized trial.

Bio‐Strath® is a plasmolyzed yeast product enriched with herbs, malt, honey and orange juice. In this study, the effect of Equi‐Strath®, the adapted product for horses, on the equine immune system was evaluated. A routine influenza booster vaccination was used as a model to study the effects of Equi‐Strath® supplementation on the immune response. Twenty healthy Franches‐Montagnes stallions with pre‐existing antibody levels were randomly divided into a study group (SG, n = 10) receiving 0.06 mL/kg bodyweight of Equi‐Strath®, and a control group (CG, n = 10), receiving the same amount of placebo, daily. The supplement and placebo were given from week 1 until week 14 of the trial. After 10 weeks, the horses were vaccinated with a commercial vaccine containing equine influenza strains of the H3N8 subtype. Antibody titres in blood were measured at day 0 before vaccination, and 14 and 32 days after vaccination. In addition, a complete blood count (CBC) was performed on day 0 and day 32. A linear increase of haemagglutination inhibition titres in both groups was observed after vaccination, but with no difference between treatment groups. CBC components remained unaffected by treatment. In conclusion, daily Equi‐Strath® supplementation did not affect the adaptive immune response in stallions after a routine commercial H3N8 influenza booster vaccination.

Inhibition of DAMP signaling as an effective adjunctive treatment strategy in pneumococcal meningitis

BackgroundPneumococcal meningitis remains a potentially lethal and debilitating disease, mainly due to brain damage from sustained inflammation. The release of danger-associated molecular patterns (DAMPs), like myeloid-related protein 14 (MRP14) and high mobility group box 1 protein (HMGB1), plays a major role in persistence of inflammation. In this study, we evaluated if paquinimod, an MRP14-inhibitor, and an anti-HMGB1 antibody can improve clinical outcome as adjunctive therapeutics in pneumococcal meningitis.MethodsWe tested the adjuvant administration of paquinimod and the anti-HMGB1 antibody in our pneumococcal meningitis mouse model assessing clinical (clinical score, open-field-test, temperature) and pathophysiological parameters (intracranial pressure, white blood cell count in CSF, bleeding area) as well as bacterial titers in blood and brain 24 h after administration and 48 h after infection. Furthermore, we explored the interactions of these two agents with dexamethasone, the standard adjuvant treatment in pneumococcal meningitis (PM), and daptomycin, a non-bacteriolytic antibiotic preventing pathogen-associated molecular pattern (PAMP) release.ResultsAdjunctive inhibition of MRP14 or HMGB1 reduced mortality in mice with PM. This effect was lost when the two anti-DAMP agents were given simultaneously, possibly due to excessive immunosuppression. Combining anti-PAMP (daptomycin) and anti-DAMP treatments did not produce synergistic results; instead, the anti-DAMP treatment alone was sufficient and superior. The combination of anti-HMGB1 with dexamethasone did not diminish the effect of the former.ConclusionsDAMP inhibition possesses good potential as an adjuvant treatment approach in PM, as it improves clinical outcome and can be given together with the standard adjuvant dexamethasone without drug effect loss in experimental PM.

Comprehensive detection of viruses in pediatric patients with acute liver failure using next-generation sequencing

BackgroundPediatric acute liver failure (PALF) is a rare and severe syndrome that frequently requires liver transplantation. Viruses are one of the most frequent causes of this disease, however, pathogenic viruses are not determined in many patients. Recently next-generation sequencing (NGS) has been applied to comprehensively detect pathogens of infectious diseases of unknown etiology. ObjectivesTo evaluate an NGS-based approach for detecting pathogenic viruses in patients with PALF or acute hepatitis of unknown etiology. Study designTo detect virus-derived DNA and RNA sequences existing in sera/plasma from patients, both DNA and RNA sequencing were performed. First, we validated the ability of NGS to detect viral pathogens in clinical serum/plasma samples, and compared different commercial RNA library preparation methods Then, serum/plasma of fourteen patients with PALF or acute hepatitis of unknown etiology were evaluated using NGS. ResultsAmong three RNA library preparation methods, Ovation RNA-Seq System V2 had the highest sensitivity to detect RNA viral sequences. Among fourteen patients, sequence reads of torque teno virus, adeno-associated virus, and stealth virus were found in the sera of one patient each, however, the pathophysiological role of these three viruses was not clarified. Significant virus reads were not detected in the remaining 11 patients. ConclusionsThis finding might be due to low virus titer in blood at the time of referral or a non-infectious cause might be more frequent. These results suggest an NGS-based approach has potential to detect viral pathogens in clinical samples and would contribute to clarification of the etiology of PALF.

There is a Fungus Among Us

SESSION TITLE: Fungal Infections 2 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Coccidioidomycosis, also known as “Valley Fever,” is a fungal infection contracted by the inhalation of spores found in the soil of the Southwestern United States, Mexico and Central America. Symptoms are nonspecific and can include cough, night sweats and dyspnea. In immunocompetent patients, infection often resolves without intervention1. This case highlights an unusual presentation of coccidioidomycosis and the importance of obtaining a thorough travel history. CASE PRESENTATION: A 36-year-old male from the Philippines with no past medical history presented to a hospital in Rhode Island with one day of shortness of breath and left-sided pleuritic chest pain. He was found to have a small left lower lobe infiltrate and pleural effusion and was discharged home on azithromycin for suspected community acquired pneumonia. He represented 9 days later with fevers and worsening dyspnea despite antibiotics and repeat chest X-ray showed an enlarging left-sided pleural effusion. Thoracentesis revealed an exudative effusion with protein 5.19 g/dL (serum 7.26), LDH 848 U/L (serum 482), with 75% lymphocytes. Cytology and fluid cultures were negative and he was discharged with Augmentin. Over the next month he had two additional hospitalizations for fevers, chest pain and recurrent left sided pleural effusion. Over this time he lost 25 lbs. On further history, the patient noted travel to both the Philippines and Thailand in the past six months. He also had travelled to California two weeks prior to his initial presentation. Extensive infectious disease evaluation was performed and he received multiple courses of broad spectrum antibiotics without improvement. He was HIV negative but was found to have a positive quantiferon gold. This raised concern for tuberculosis, however, induced sputum and pleural fluid samples were all negative for acid fast bacilli and pleural fluid adenosine deaminase was only moderately elevated at 29.7 U/L (normal < 9.2). Given his persistent symptoms he ultimately underwent pleural biopsy which revealed granulomatous inflammation and fungal organisms consistent with Coccidioides immitis (image 1). Blood titres for coccidioides, sent after biopsy, peaked at 1:512. After three months of anti-fungal therapy his symptoms have resolved. DISCUSSION: Coccidioidomycosis is seldom seen in the northeastern United States, and rarely presents as a recurrent pleural effusion. The diagnosis is often delayed, as in this case, due to failure to consider this infection in the differential diagnosis. In this case we were mislead by the patient’s positive quantiferon gold and recent travel to a tuberculosis endemic area and overlooked his more recent travel to the west coast. CONCLUSIONS: This case serves as a reminder to take the time to record a thorough travel history, and recognize when diagnostic anchoring obscures clinical judgment. Reference #1: 1. Clin Infect Dis. 2016 Sep;63(6):e112-46 DISCLOSURE: The following authors have nothing to disclose: Dennis Guadarrama, Humnah Khudayar, Melissa Tukey, Andrew Schiff No Product/Research Disclosure Information

Voltage gated potassium channel antibody(VGKC)-associated encephalopathy and psychiatric symptoms (case report)

Introduction and ObjectivesThe limbic system is primarily responsible for modulating behaviour, emotions and neuro-endocrine functions. Limbic encephalopathy involves this part of the brain and is characterised by the acute or sub-acute onset of seizures, recent memory loss, confusion and psychiatric symptoms. Here we describe an unusual presentation of a well-functioning elderly man, who presented with sudden onset of confusion, cognitive impairment, treatment resistant hyponatremia, seizures and psychiatric symptoms.Methods (Presentation)This 79 year old gentleman, previously well and independent was admitted to the acute hospital with a 3 week history of sudden onset of confusion, odd behaviour and weight loss. On admission he was hyponatremic (Na-118), developed treatment resistant seizures and progressive cognitive impairment. He was referred to the Liaison Psychiatry team with increasing paranoia, agitation and persecutory delusions.ResultsMRI and CT brain remained normal. Lumbar puncture revealed a positive VGKC antibody and his blood titres for VGKC was more than 3000. His hyponatremia and seizures remained chronic, but improved with plasmapheresis, oral corticosteroids and cyclophosphamide. He was commenced on aripiprazole for psychiatric symptoms, but was transferred to the acute psychiatric unit after being detained under section 2 of the MHA due to risks of aggression and absconsion.ConclusionsPsychiatric symptoms related to this form of encephalitis have not been emphasised in literature. His aggression improved over time on aripiprazole, but was transferred to a residential care home setting due to persisting cognitive deficits and social care needs This case highlights the importance of recognising multimorbidity, joint working and more research required in the area.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Time correlation between mononucleosis and initial symptoms of MS.

Objective:To determine the average age of MS onset vs the age at which Epstein-Barr infection has previously occurred and stratify this analysis by sex and the blood level of Epstein-Barr nuclear antigen 1 (EBNA1) antibody.Methods:Using infectious mononucleosis (IM) as a temporal marker in data from the Swedish epidemiologic investigation of MS, 259 adult IM/MS cases were identified and then augmented to account for “missing” childhood data so that the average age of MS onset could be determined for cases binned by age of IM (as stratified by sex and EBNA1 titer level).Results:Mean age of IM vs mean age of MS reveals a positive time correlation for all IM ages (from ∼5 to ∼30 years), with IM-to-MS delay decreasing with increased age. When bifurcated by sex or EBNA1 blood titer levels, males and high-titer subpopulations show even stronger positive time correlation, while females and low-titer populations show negative time correlation in early childhood (long IM/MS delay). The correlation becomes positive in females beyond puberty.Conclusions:IM/MS time correlation implies causality if IM is time random. Alternative confounding models seem implausible, in light of constraints imposed by time-invariant delay observed here. Childhood infection with Epstein-Barr virus (EBV) in females and/or those genetically prone to low EBNA1 blood titers will develop MS slowly. Males and/or high EBNA1-prone develop MS more rapidly following IM infection at all ages. For all, postpubescent EBV infection is critical for the initiation and rapid development of MS.

FOSL1 Inhibits Type I Interferon Responses to Malaria and Viral Infections by Blocking TBK1 and TRAF3/TRIF Interactions.

ABSTRACTInnate immune response plays a critical role in controlling invading pathogens, but such an immune response must be tightly regulated. Insufficient or overactivated immune responses may lead to harmful or even fatal consequences. To dissect the complex host-parasite interactions and the molecular mechanisms underlying innate immune responses to infections, here we investigate the role of FOS-like antigen 1 (FOSL1) in regulating the host type I interferon (IFN-I) response to malaria parasite and viral infections. FOSL1 is known as a component of a transcription factor but was recently implicated in regulating the IFN-I response to malaria parasite infection. Here we show that FOSL1 can act as a negative regulator of IFN-I signaling. Upon stimulation with poly(I:C), malaria parasite-infected red blood cells (iRBCs), or vesicular stomatitis virus (VSV), FOSL1 “translocated” from the nucleus to the cytoplasm, where it inhibited the interactions between TNF receptor-associated factor 3 (TRAF3), TIR domain-containing adapter inducing IFN-β (TRIF), and Tank-binding kinase 1 (TBK1) via impairing K63-linked polyubiquitination of TRAF3 and TRIF. Importantly, FOSL1 knockout chimeric mice had lower levels of malaria parasitemia or VSV titers in peripheral blood and decreased mortality compared with wild-type (WT) mice. Thus, our findings have identified a new role for FOSL1 in negatively regulating the host IFN-I response to malaria and viral infections and have identified a potential drug target for controlling malaria and other diseases.

Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

BackgroundThe target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development.MethodsA case control study nested in a birth cohort (2002–07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres.ResultsThe mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (<3months age group) but not significant (P = 0.3).ConclusionsFrom this study, there is no strong evidence of protection by maternal RSV specific antibodies from severe RSV disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

The prophylactic effects of human IgG derived from sera containing high anti-PcrV titers against pneumonia-causing Pseudomonas aeruginosa

ABSTRACTThe PcrV cap structure of the type III secretory apparatus of Pseudomonas aeruginosa is a vaccine target. Human immunoglobulin G (IgG) molecules extracted from sera containing high or low anti-PcrV titers were tested for their effects against P. aeruginosa pneumonia in a mouse model. Among 198 volunteers, we selected the top 10 high anti-PcrV titer sera and the bottom 10 low anti-PcrV titer sera and extracted the IgG fraction from each serum sample. First, we examined the effects of the IgG against virulent P. aeruginosa. A lethal dose of P. aeruginosa premixed with saline, low titer human IgG, high titer human IgG, or rabbit-derived polyclonal anti-PcrV IgG was intratracheally administered into the lungs of mice, and their survival and lung inflammation were evaluated for 24 h. The high anti-PcrV titer human IgG had a prophylactic effect. Next, the prophylactic effects of intravenous administration of extracted and pooled high or low anti-PcrV titer human IgG were examined. Here, prophylactic intravenous administration of pooled high anti-PcrV titer human IgG, which showed binding capacity to P. aeruginosa PcrV, was more effective than the administration of its low titer pooled equivalent, and the measured physiological and inflammatory parameters correlated with the anti-PcrV titer levels. This result indirectly implies that high anti-PcrV titers in blood can help to protect against virulent P. aeruginosa infections. In addition, the IgG fractions from such high titer sera have potential to be a source of specific intravenous immunoglobulin products for passive vaccination against virulent P. aeruginosa infections.

Evolutionary Endocrinology of Hormonal Rhythms: Juvenile Hormone Titer Circadian Polymorphism in Gryllus firmus.

Daily rhythms for hormonal traits are likely widespread and important aspects of organismal (e.g., life history) adaptation. Yet they remain substantially understudied, especially with respect to variable rhythms within species. The cricket, Gryllus firmus, exhibits a genetically polymorphic circadian rhythm for the blood titer of the key hormone, juvenile hormone (JH). Gryllus firmus is also wing-polymorphic, consisting of a dispersing morph that delays reproduction and a flightless morph with substantially enhanced egg production. JH circadian phenotype strongly covaries with morph type: The blood JH titer is strongly rhythmic in multiple populations artificially-selected for the dispersing morph (LW(f) = long wings with functional flight muscles) and is essentially arrhythmic in populations selected for the SW (short-winged) morph. Association between JH titer cycle and LW(f) morph is also found in natural populations of G. firmus and in several related species in the field. This is one of the very few studies of endocrine titer variation in natural populations of an insect. The morph-specific cycle is underlain by a circadian rhythm in hormone biosynthesis, which in turn is underlain by a rhythm in a brain neuropeptide regulator of JH biosynthesis. The morph-specific JH titer circadian cycle is also strongly correlated with a morph-specific daily rhythm in global gene expression. This is currently the only example of a genetically-variable hormone circadian rhythm in both the laboratory and field that is strongly associated with an ecologically important polymorphism. The extensive information on the underlying causes of the morph-specific JH titer rhythm, coupled with the strong association between the JH circadian rhythm and wing polymorphism makes this system in G. firmus an exceptional experimental model to investigate the mechanisms underlying circadian hormonal adaptations. Genetic polymorphism for the JH titer circadian rhythm in G. firmus is discussed in context of circadian rhythms for endocrine traits reported for vertebrates and insects. Consequences of the failure to identify endocrine circadian rhythms on the accuracy of estimation of quantitative-genetic parameters, such as heritability and correlations between hormonal and fitness-related traits, are also discussed.

Equine arteritis virus antibody cELISA, a well-validated alternative to the World Organization for Animal Health (OIE)-prescribed virus neutralization test

and negative, respectively. Regarding the buffy coat samples, iiRTPCR detected EIAV nucleic acid in 31/56 AGID positive samples, while 108/109 AGID negative samples tested negative by iiRTPCR. Total agreement was 84.24%. When whole blood samples were evaluated, a total of 16 iiRT-PCR positive and 15 iiRT-PCR negative out of 31 AGID positive samples were obtained. Additionally, EIAV nucleic acid was not detected in 25 AGID negative samples .Total agreement was 73.21% for this sample type. When evaluating the accuracy of EIAV iiRT-PCR and qPCR, 28/165 and 130/165 buffy coat samples tested positive and negative by both assays, respectively. Five iiRT-PCR positive samples were negative by qPCR and two qPCR positive samples were negative by iiRTPCR. Thus, EIAV iiRT-PCR showed more than 95% agreement with qPCR results. It has been demonstrated that the absence of clinical signs is correlated with very low, frequently undetectable viremia. Therefore, EIAV iiRT-PCR appears to be a promising tool to identify infected horses including those experiencing low infectivity titers in blood. Furthermore, as initial EIAV replication rates are frequently high, recently infected equids pose a considerable transmission risk long before seroconversion. In our study, a horse was determined seronegative by AGID, but was identified as EIAV infected by iiRT-PCR. Thus, EIAV iiRT-PCR could be considered as an alternative diagnostic tool in the implementation of control strategies during an EIA outbreak in the low prevalence area of our country.

Epstein–Barr virus reactivation in extranodal natural killer/T-cell lymphoma patients: a previously unrecognized serious adverse event in a pilot study with romidepsin

Romidepsin, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of relapsed and refractory peripheral T-cell lymphoma. However, the efficacy and safety of romidepsin has never been studied in patients with relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We conducted an open-label, prospective pilot study to evaluate the efficacy and feasibility of romidepsin in the treatment of patients with ENKTL. The treatment was intravenous infusion of romidepsin (14 mg/m(2)) for 4 h on days 1, 8, and 15 of a 28-day cycle, and was repeated until disease progression or the occurrence of unacceptable toxicity. A total of five patients enrolled on to this pilot study. However, three patients developed fever and elevated liver enzyme and bilirubin levels immediately after their first administration of romidepsin. We suspected that these events were associated with Epstein-Barr virus (EBV) reactivation because of the rapidly elevated EBV DNA titers in blood from these patients. An in vitro study with the ENKTL cell line SNK-6 cells also showed that HDAC inhibitors including romidepsin increased the copy number of EBV DNA in a dose-dependent manner. These findings suggested that romidepsin-induced histone acetylation reversed the repressed state of the genes required for EBV reactivation and that romidepsin treatment may have caused EBV reactivation in EBV-infected tumor cells in ENKTL patients. Therefore, we discontinued the enrollment of patients into this pilot study. Our study suggests that the use of romidepsin may cause severe EBV reactivation in patients with ENKTL.