Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.     

Urban woodland habitat is important for tick presence and density in a city in England

Urban green spaces provide an opportunity for contact between members of the public and ticks infected with pathogens. Understanding tick distribution within these areas and the drivers for increased tick density or Borrelia infection are important from a risk management perspective. This study aimed to generate data on tick presence, nymph density and Borrelia infection across a range of urban green space habitats, in order to identify those that may potentially present a higher risk of Lyme borreliosis to members of the public. Several sites were visited across the English city of Bath during 2015 and 2016. Tick presence was confirmed in all habitats surveyed, with increased likelihood in woodland and woodland edge. Highest nymph densities were also reported in these habitats, along with grassland during one of the sampling years. Adult ticks were more likely to be infected compared to nymphs, and the highest densities of infected nymphs were associated with woodland edge habitat. In addition to Lyme borreliosis causing Borrelia genospecies, Borrelia miyamotoi was also detected at several sites. This study adds to the growing evidence that urban green space habitats present a public health risk from tick bites, and this has implications for many policy areas including health and wellbeing, climate adaptation and urban green space planning.     

Hepatitis B virus DNA in the fingernails and hair of children with acute hepatitis B

Hepatitis B virus (HBV) DNA is detectable in the nails and hair of patients with chronic HBV infection. However, it remains unclear whether HBV DNA can be detectable in the nails and hair of patients with acute HBV infection. We encountered two cases of children with acute HBV infection. HBV DNA in the nails and hair from the two children was evaluated by real-time PCR. To clarify the characteristics of HBV DNA, full-length HBV genome sequencing and phylogenetic tree analysis were performed. The levels of serum HBV DNA in children of cases 1 and 2 at day 0 were 7.6 Log IU/mL and 7.4 Log IU/mL, respectively. Nail HBV DNA was detected in both children (case 1: 4.6 Log IU/mL at day 0, case 2: 5.5 Log IU/mL at day 14). Moreover, hair HBV DNA was detectable in case 2 (4.0 Log IU/mL at day 14). Serum HBV DNA became undetectable within approximately 3–4 months after the first hospital visit. After the resolution of HBV viremia, nail and hair HBV DNA became undetectable. The sequence analysis of serum, nail and hair HBV DNA showed the same HBV genotype in each case (case1: genotype C, case 2: genotype A). In case 1, 3 nucleotides were different in the full-genome HBV sequence between the serum and nails. In case 2, the full-genome HBV sequences were identical among the serum, nails and hair. In conclusion, HBV DNA was detectable in nails and hair of children with acute HBV infection.     

Molecular and MALDI-TOF MS characterisation of Hyalomma aegyptium ticks collected from turtles and their associated microorganisms in Algeria

The identification of ticks and their associated pathogens is important for knowledge on tick-borne diseases. The objective of this study was to use morphological, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and/or molecular biology tools to identify ticks collected from turtles in north-eastern Algeria, as well as to investigate the microorganisms associated with these ticks. A total of 471 adult ticks were collected and identified morphologically as Hyalomma aegyptium, of which 248 (52.7%) were female and 223 (47.3%) were male. amongst them, 230 specimens were randomly selected for molecular and MALDI-TOF MS analysis. Molecular biology confirmed that our ticks were Hy. aegyptium. MALDI-TOF MS analysis revealed that 100% of the spectra were of excellent quality. Four spectra were selected to update our own database MALDI-TOF MS arthropod. The blind test of the 226 remaining spectra showed that all ticks were correctly identified, with scores ranging from 1.774 to 2.655 with a mean of 2.271 ± 0.16 of which, 223 (98.6%) had log score value (LSV)>1.8. Molecular biology screening showed that the ticks carried the DNA of Borrelia turcica, Rickettsia africae, Rickettsia aeschlimannii, Rickettsia sibirica mongolitimonae and with the Anaplasmataceae were close to a potentially new, undescribed Ehrlichia sp. This study confirms that MALDI-TOF MS is a reliable tool for the identification of ticks and that ticks collected from turtles in Algeria are carriers of several species of microorganisms which may be responsible for diseases in humans and animals.     

ONRAB® oral rabies vaccine is shed from,but does not persist in,captive mammals

ONRAB® is a human adenovirus rabies glycoprotein recombinant vaccine developed to control rabies in wildlife. To support licensing and widespread use of the vaccine, safety studies are needed to assess its potential residual impact on wildlife populations. We examined the persistence of the ONRAB® vaccine virus in captive rabies vector and non-target mammals. This research complements work on important rabies vector species (raccoon, striped skunk, and red fox) but also adds to previous findings with the addition of some non-target species (Virginia opossum, Norway rats, and cotton rats) and a prolonged period of post vaccination monitoring (41 days). Animals were directly inoculated orally with the vaccine and vaccine shedding was monitored using quantitative real-time PCR applied to oral and rectal swabs. ONRAB® DNA was detected in both oral and rectal swabs from 6 h to 3 days post-inoculation in most animals, followed by a resurgence of shedding between days 17 and 34 in some species. Overall, the duration over which ONRAB® DNA was detectable was shorter for non-target mammals, and by day 41, no animal had detectable DNA in either oral or rectal swabs. All target species, as well as cotton rats and laboratory-bred Norway rats, developed robust humoral immune responses as measured by competitive ELISA, with all individuals being seropositive at day 31. Similarly, opossums showed good response (89% seropositive; 8/9), whereas only one of nine wild caught Norway rats was seropositive at day 31. These results support findings of other safety studies suggesting that ONRAB® does not persist in vector and non-target mammals exposed to the vaccine. As such, we interpret these data to reflect a low risk of adverse effects to wild populations following distribution of ONRAB® to control sylvatic rabies.     

Hepatitis B surface antigen seroprevalence among pre- and post-vaccine cohorts in Cambodia, 2017

Background: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children.Methods: A cross-sectional multi-stage cluster survey was conducted among children born during 2010–2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children’s failure to receive timely (within 24 h) vaccination were analysed by multivariate logistic analysis.Findings: A total of 2,520 children 5–7 years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered ≤ 24 h. Birth at home or “other” location were independent risk factors for children’s failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%–5.45%) among mothers and 0.56% (95%CI: 0.32%–0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%–14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%–18.11%).Interpretation: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5 years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030.Funding: As per sources of funding.     

Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development

Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development.     

Defining hard-to-reach populations for vaccination

Extending the benefits of vaccination to everyone who is eligible requires an understanding of which populations current vaccination efforts have struggled to reach. A clear definition of “hard-to-reach” populations – also known as high-risk or marginalized populations, or reaching the last mile – is essential for estimating the size of target groups, sharing lessons learned based on consistent definitions, and allocating resources appropriately. A literature review was conducted to determine what formal definitions of hard-to-reach populations exist and how they are being used, and to propose definitions to consider for future use. Overall, we found that (1) there is a need to distinguish populations that are hard to reach versus hard to vaccinate, and (2) the existing literature poorly defined these populations and clear criteria or thresholds for classifying them were missing. Based on this review, we propose that hard-to-reach populations be defined as those facing supply-side barriers to vaccination due to geography by distance or terrain, transient or nomadic movement, healthcare provider discrimination, lack of healthcare provider recommendations, inadequate vaccination systems, war and conflict, home births or other home-bound mobility limitations, or legal restrictions. Although multiple mechanisms may apply to the same population, supply-side barriers should be distinguished from demand-side barriers. Hard-to-vaccinate populations are defined as those who are reachable but difficult to vaccinate due to distrust, religious beliefs, lack of awareness of vaccine benefits and recommendations, poverty or low socioeconomic status, lack of time to access available vaccination services, or gender-based discrimination. Further work is needed to better define hard-to-reach populations and delineate them from populations that may be hard to vaccinate due to complex refusal reasons, improve measurement of the size and importance of their impact, and examine interventions related to overcoming barriers for each mechanism. This will enable policy makers, governments, donors, and the vaccine community to better plan interventions and allocate necessary resources to remove existing barriers to vaccination.     

Vaccinations in prison settings: A systematic review to assess the situation in EU/EEA countries and in other high income countries

IntroductionIn 2016, more than 600,000 persons were being held in EU/EEA correctional facilities on a given day. People in prison may be at risk of vaccine-preventable diseases. While vaccination recommendations for people in prison exist, little is known on coverage and implementation options.MethodsWe performed a systematic review on existing evidence on vaccination in prison settings in the EU/EEA. We searched peer-reviewed and grey literature following international methodology and reporting standards, to gather records published between 1980 and 2016 in all languages. We analysed quantitative (acceptance, uptake, cost-effectiveness) and qualitative (barriers) outcomes.ResultsOut of 7041 identified records, 19 full-text articles were included from peer-reviewed literature and two from grey literature. Of these, 18 reported on hepatitis A and/or B virus (HAV/HBV), two on influenza and one on MMR vaccination. Two studies on HAV vaccine reported varying acceptance (5–91%) and uptake rates (62.9–70.5%). Seven studies reported on HBV vaccination. A comparative study showed a significantly higher uptake of the third HBV vaccine dose with the very rapid (63%) compared to the standard schedule (20%). HBV vaccination was generally well accepted (54–100%), whereas uptake was variable (dose 1:23–100%, dose 2:48–92%, dose 3:19–80%). One study on the combined HAV/HBV vaccine reported an acceptance rate of 34%, and declining uptake following dose 1. One study on influenza vaccine showed an uptake of 42–46%, while another reported a MMR vaccine acceptance of 80% and an uptake of 74%. Overall, main reasons for non-vaccination included release from/or transfer between prisons, and refusal.ConclusionsThis systematic review highlighted important knowledge gaps and operational challenges for vaccination in prison settings. Vaccination is an effective measure that warrants comprehensive and tailored implementation to reduce the preventable disease burden, avoid risks of large outbreaks of vaccine-preventable diseases, and contribute to health equity for people in prison.