Vitamin D deficiency or supplementation and the risk of human herpesvirus infections or reactivation: a systematic review protocol.

INTRODUCTION: Human herpesviruses induce lifelong latent infections and may reactivate as the immune system deteriorates. Recent studies have suggested that vitamin D, an essential element of bone health, may have some effect of protecting against infections, but investigations of its potential to prevent herpesvirus infection or reactivation are limited. We will review the current literature examining vitamin D and the risk of herpesvirus infections or reactivation. METHODS AND ANALYSIS: Our systematic review will address two research questions: (1) Do deficient/insufficient serum vitamin D levels increase the risk of herpesvirus infections and (2) Does vitamin D supplementation protect against herpesvirus infections? We will include only intervention studies with control groups, cohort studies and case-control studies. We will use subject headings and keywords to search for synonyms of 'vitamin D' and 'herpesviruses' (including herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus and human herpesviruses type 6, 7 and 8) in Medline, Embase, Global Health, Web of Science, Scopus and Cochrane Central Register of Controlled Trials, and the grey literature databases Open Grey, EThOS and BASE from inception to 31 August 2019. References to the included articles and relevant systematic reviews will also be examined. Two reviewers will independently screen the study titles and abstracts, and examine the full texts to decide the final eligibility. They will independently extract data from the studies and assess bias using the Cochrane Collaboration approach. A third researcher will solve any discrepancies. The results will be narratively synthesised; if an adequate number of studies is included and the homogeneity between studies is acceptable, a meta-analysis will be performed. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework, and display the results in a summary of findings table. ETHICS AND DISSEMINATION: Ethical review is not required for a systematic review. We will publish the results in a peer-review journal. Any amendments to the protocol will be recorded in the supplementary section. PROSPERO REGISTRATION NUMBER: CRD42019130153.

High seroprevalence of human herpesvirus type 8 in patients with end-stage renal disease in Taiwan.

BACKGROUND: Human herpesvirus type 8 (HHV-8) is the aetiologic agent of Kaposi's sarcoma (KS). The incidence of KS in renal transplant patients is much higher than in healthy controls. The risk is even higher among recipients seropositive for HHV-8 before transplantation. Patients with end-stage renal disease (ESRD) are immunocompromised and are candidates for renal transplantation, but HHV-8 seroprevalence in ESRD patients has not been well documented. OBJECTIVES: This study aimed to evaluate HHV-8 seroprevalence in ESRD patients in a cohort in Taiwan. STUDY DESIGN: Blood samples collected from 149 ESRD patients and 149 age- and sex-matched healthy controls were analysed for HHV-8 antibody with immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) and for HHV-8 DNA with polymerase chain reaction. RESULTS: Seropositivity and titres for HHV-8 antibodies with IFA as well as seropositivity with ELISA were significantly greater in ESRD patients than in healthy controls (P=0.006, 0.001 and 0.003, respectively). Patients with a history of taking herbal medicine had significantly greater ELISA positivity than those without such a history (P=0.004). ELISA positives, particularly patients, had much higher IFA antibody titres than ELISA negatives (P<0.0001). Seropositivity in ESRD patients was not related to lymphopaenia, monocytosis, dialysis duration or a history of transfusion. Two diabetic ESRD patients were positive for HHV-8 DNA. CONCLUSIONS: ESRD patients had significantly greater HHV-8 seropositivity than healthy controls in Taiwan. This association seems to be related to the geographic location of the cohort and invites further studies for the early association of HHV-8 infection in ESRD patients and risk for KS.

Case-control study of a multistate equine herpesvirus myeloencephalopathy outbreak.

BACKGROUND: A large multistate outbreak of equine herpesvirus myeloencephalopathy (EHM) occurred in May 2011 among horses that participated in a competitive event. OBJECTIVE: To identify EHM risk factors among horses with a common exposure venue. ANIMALS: A total of 123 horses: 19 horses with EHM, 14 equine herpesvirus-1 cases with no reported neurologic signs, and 90 control horses. METHODS: EHM case survey data were compared with data from EHV-1 cases with no neurologic signs and healthy controls using univariable and multivariable methods. RESULTS: Significant factors associated with higher risk for EHM compared with EHV-1 cases with no neurologic signs were (1) greater number of biosecurity risks at the event, (2) female sex, (3) increasing number of classes competed in at the event, and (4) an interaction between sex and number of classes competed in. In the EHM versus controls comparison, in addition to sex and biosecurity risks, factors associated with higher EHM risk included EHV-1 vaccination in the 5 weeks before the event and increasing number of events attended in April 2011; zinc dietary supplementation was associated with decreased risk. An interaction between sex and the number of events attended in April 2011 also was significant. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings from this study suggest that dietary zinc supplementation may be associated with decreased risk of EHM. Several factors were associated with increased risk of EHM. Additional investigations of factors associated with risk of EHM are warranted to evaluate the importance of these factors in this complex disease of horses.

Herpesvirus infections and allergic sensitization in children of families with anthroposophic and non-anthroposophic lifestyle - the ALADDIN birth cohort.

BACKGROUND: Growing up in families with an anthroposophic lifestyle has been associated with reduced risk of allergic disease in children. The aim of this report was to assess whether children with this lifestyle are infected earlier with Epstein-Barr virus (EBV), which has been associated with reduced risk of allergic disease, and three other herpesviruses potentially involved in allergy development, namely Human herpesvirus 6 (HHV6), Human herpesvirus 7 (HHV7) and cytomegalovirus (CMV). METHODS: Within the ALADDIN (Assessment of Lifestyle and Allergic Disease During Infancy), birth cohort study 157 children were categorized according to lifestyle into anthroposophic and non-anthroposophic. IgG-levels for EBV, HHV6, HHV7 and CMV were determined in plasma samples collected at ages 12 and 24 months and from parents. IgE levels against seven common allergens were analyzed at 24 months. RESULTS: No significant differences in seroprevalence of EBV, HHV7 or CMV were detected at any age between the two lifestyle groups. The seroprevalence of HHV6 was significantly lower in the anthroposophic group at 24 months of age (74.6% vs. 87.5%, p-value 0.048). Further, no significant associations between allergic sensitization and seropositivity to any of the viruses were detected; however, an interaction effect of lifestyle could not be ruled out. CONCLUSIONS: Our results indicate that there is no strong influence of exposure to the anthroposophic lifestyle on the time for infection with EBV, HHV6, HHV7 or CMV. These infections can therefore not be assumed to be important factors in the allergy-protective effect of this lifestyle.

Implementing a probabilistic definition of freedom from infection to facilitate trade of livestock: putting theory into praxis for the example of bovine herpes virus-1.

International trade of livestock and livestock products poses a significant potential threat for spread of diseases, and importing countries therefore often require that imported animals and products are free from certain pathogens. However, absolute freedom from infection cannot be documented, since all test protocols are imperfect and can lead to false-negative results. It is possible instead to estimate the "probability of freedom from infection" and its opposite, the probability of infection despite having a negative test result. These probabilities can be estimated based on a pre-defined target prevalence, known surveillance efforts in the target population and known test characteristics of any pre-export test. Here, calculations are demonstrated using the example of bovine herpes virus-1 (BoHV-1). In a population that recently became free of BoHV-1 without using vaccination, the probability of being infected of an animal randomly selected for trade is 800 per 1 million and this probability is reduced to 64 (95% probability interval PI 6-161) per 1 million when this animal is tested negatively prior to export with a gB-ELISA. In a population that recently became free of BoHV-1 using vaccination, the probability of being infected of an animal randomly selected for trade is 200 per 1 million, and this probability can be reduced to 63 (95% PI 42-87) when this animal is tested negatively prior to export with a gE-ELISA. Similar estimations can be made on a herd level when assumptions are made about the herd size and the intensity of the surveillance efforts. Subsequently, the overall probability for an importing country of importing at least 1 infected animal can be assessed by taking into account the trade volume. Definition of the acceptable level of risk, including the probability of false-negative results to occur, is part of risk management. Internationally harmonized target prevalence levels for the declaration of freedom from infection from selected pathogens provide a significant contribution to the facilitation of international trade of livestock and livestock products by allowing exporting countries to design tailor-made output-based surveillance programs, while providing equivalent guarantees regarding the probability of freedom from infection of the population. Combining this with an approach to assess the overall probability of introducing at least 1 infected animal into an importing country during a defined time interval will help importing countries to achieve their desired level of acceptable risk and will help to assess the equivalence of animal health and food safety standards between trading partners.

Evaluation of bloodsucking arthropod bite as possible risk co-factor in Human herpesvirus-8 transmission route.

Human herpesvirus-8 non-sexual transmission occurs primarily from mother-to-child. The viral load in saliva is higher than in other human fluids. Moreover, there is evidence that bloodsucking arthropod bites induce an inflammatory/immune response that facilitates viral replication. We aim to explore possible risk factors in mother-to-child HHV-8 transmission associated with traditional methods which involve the use of saliva to relieve the irritation and skin reaction caused by arthropod bites. We administered questionnaires to 2244 children from several African countries and Italy. Descriptive statistics and logistic regression were used in the analysis of the answers to evaluate the relationships between the use of traditional methods and other risk factors. The use of traditional methods is high in Cameroon (63.0%) and Uganda (39.9%), intermediate in Senegal (26.7%) and Italy (21.7%), low in Madagascar (6.7%). Statistical analyses show significant direct relationships between the use of traditional methods, skin reactions to the bite and their duration in Cameroon, Uganda and Senegal. The use of saliva and herbs applied by the mothers on the child's skin, is a common habit in Africa. If this practice plays a role in the HHV-8 transmission, then, it could provide the basis for interventions capable of reducing the health impact of the infection in children in tropical areas.

Oral supplementation with L-lysine did not prevent upper respiratory infection in a shelter population of cats.

Cats in animal shelters are highly susceptible to infection by feline herpesvirus (FHV) by virtue of their stress and close proximity to other cats. Animal shelters take several different approaches to prevent FHV-related upper respiratory infections (URIs), including empirically treating all cats with L-lysine, a supplement believed to prevent the replication of FHV and, therefore, manifestations of herpesvirus infections. In this study we tested oral supplementation of L-lysine as a means to prevent URIs. One hundred and forty-four cats were treated with L-lysine in a small amount of canned food once daily. A 'no treatment' group of 147 cats received no lysine during the course of the study. The development of conjunctivitis or URI was tracked between the two groups. In all measures, there was no effect between the two groups, suggesting that lysine was not able to prevent URI or conjunctivitis in our shelter situation. Cats entering shelters encounter stressors that may make them more susceptible to FHV reactivation or infection. Infection control and control of fomite transmission are also key to keeping cats healthy in a group housing situation. The finding that lysine did not prevent URI in this animal shelter suggests that shelters may better use their resources by finding ways to decrease stress among their feline population, focusing on proper infection control measures, and limiting fomite transmission of disease.

A stochastic simulation model to determine the sample size of repeated national surveys to document freedom from bovine herpesvirus 1 (BoHV-1) infection.

BACKGROUND: International trade regulations require that countries document their livestock's sanitary status in general and freedom from specific infective agents in detail provided that import restrictions should be applied. The latter is generally achieved by large national serological surveys and risk assessments. The paper describes the basic structure and application of a generic stochastic model for risk-based sample size calculation of consecutive national surveys to document freedom from contagious disease agents in livestock. METHODS: In the model, disease spread during the time period between two consecutive surveys was considered, either from undetected infections within the domestic population or from imported infected animals. The @Risk model consists of the domestic spread in-between two national surveys; the infection of domestic herds from animals imported from countries with a sanitary status comparable to Switzerland or lower sanitary status and the summary sheet which summed up the numbers of resulting infected herds of all infection pathways to derive the pre-survey prevalence in the domestic population. Thereof the pre-survey probability of freedom from infection and required survey sample sizes were calculated. A scenario for detection of infected herds by general surveillance was included optionally. RESULTS: The model highlights the importance of residual domestic infection spread and characteristics of different import pathways. The sensitivity analysis revealed that number of infected, but undetected domestic herds and the multiplicative between-survey-spread factor were most correlated with the pre-survey probability of freedom from infection and the resulting sample size, respectively. Compared to the deterministic pre-cursor model, the stochastic model was therefore more sensitive to the previous survey's results. Undetected spread of infection in the domestic population between two surveys gained more importance than infection through animals of either import pathway. CONCLUSION: The model estimated the pre-survey probability of freedom from infection accurately as was shown in the case of infectious bovine rhinotracheitis (IBR). With this model, a generic tool becomes available which can be adapted to changing conditions related to either importing or exporting countries.

Epidemiological studies of equine herpesvirus 1 (EHV-1) in Thoroughbred foals: a review of studies conducted in the Hunter Valley of New South Wales between 1995 and 1997.

Sero-epidemiological studies conducted between 1995 and 1997 on two large Thoroughbred stud farms in the Hunter Valley of NSW showed clear evidence of EHV-1 infection in foals as young as 30 days of age. Similarly, serological evidence suggested that these foals were infected with EHV-1 from their dams or from other lactating mares in the group, with subsequent foal to foal spread of infection prior to weaning. These studies also provided evidence of EHV-1 infection of foals at and subsequent to weaning, with foal to foal spread of EHV-1 amongst the weanlings. These data indicated that the mare and foal population was a reservoir of EHV-1, from which new cases of infection propagated through the foal population both before and after weaning. The results of these studies support the long standing management practices of separating pregnant mares from other groups of horses to reduce the incidence of EHV-1 abortion. Also, these results have important implications for currently recommended vaccination regimens, as the efficacy of vaccination in already latently infected horses is unknown.

Risk factors in bone marrow transplant recipients with leukaemia. Increased relapse risk in patients treated with ciprofloxacin for gut decontamination.

Three hundred and six patients with low- and intermediate-risk leukaemias undergoing allogeneic BMT between 1980 and March 1996 were studied regarding transplantation-related mortality (TRM), relapse, and leukaemia-free survival (LFS). Among the patients were 262 recipients of marrow from HLA-identical siblings and 44 patients receiving marrow from HLA-A, -B, and -DR identical unrelated donors. Between 1986 and 1993, 153 adult patients received ciprofloxacin continuously during Cy conditioning, but since November 1993 ciprofloxacin has not been given until after Cy treatment. TRM at 5 yr showed an incidence of 30%. Significant risk factors in Cox regression multivariate analysis comprised acute GVHD grades II-IV (p < 0.0001), seropositivity for 3-4 herpes viruses prior to BMT (p = 0.002), intermediate risk disease (p = 0.008), female donor to male recipient (p = 0.015), and a donor age over 17 yr (p = 0.025). The risk of relapse was studied from 90 d after BMT, and the overall 5-yr incidence was 32%. Significant risk factors comprised acute leukaemia, as compared to CML (p = 0.003), total body irradiation (TBI) compared to busulphan treatment (p = 0.011), gram-negative prophylaxis with ciprofloxacin during cyclophosphamide (Cy) conditioning (p = 0.024), GVHD prophylaxis using a combination of methotrexate (MTX) and cyclosporine (CSA), compared to monotherapy (p = 0.037) and absence of chronic GVHD (p = 0.050). The 5-yr probability of relapse in patients receiving ciprofloxacin prophylaxis during Cy conditioning was 40%, compared to 24% in patients not receiving this treatment (p = 0.01). Overall, LFS at 5 yr was 49%. LFS was evaluated from day 30 after BMT until relapse or death of the patient. We found no difference in TRM, relapse or LFS between recipients of HLA-identical sibling or unrelated bone marrow, risk factors significantly associated with an inferior LFS included acute GVHD grades II-IV (p = 0.0002), intermediate risk disease (p = 0.003), donor seropositivity for 3-4 herpes viruses (p = 0.046), and TBI conditioning (p = 0.048).