What Influences Health Professionals’ Recommendations for Non-Scheduled Childhood Vaccinations? A Qualitative Study of Health Professionals’ Perspectives in Three Provinces of China

Recommendations by health professionals are important for vaccines that are not included in national schedules. This study explored health professionals’ perspectives on recommending non-scheduled (user-fee) childhood vaccinations in China, identifying key influences on professionals’ interactions with caregivers. We conducted individual semi-structured interviews with 20 health professionals from three provinces in China and analyzed data thematically using deductive and inductive coding. Health professionals from all three provinces were uncomfortable about being perceived to encourage parents to accept vaccines that incurred a fee. They provided information about non-scheduled vaccines but emphasized parental autonomy in decision-making. Rural parents were less aware of unscheduled vaccines and health professionals were more likely to encourage parents living in more affluent areas to consider these vaccines; varicella vaccine was preferred by parents as a way of preventing school absence. Economic incentives for unscheduled vaccines were given to staff at most study sites, although the amount given varied widely. These variations meant that staff receiving lower incentives were not motivated to promote non-scheduled vaccines if their workload was high; on the contrary, those receiving higher incentives were more likely to promote these vaccines. Health professionals need more guidance on how to recommend unscheduled vaccines in an informative, positive and appropriate manner. It is evident that parents’ awareness of these vaccines, and their economic circumstances, influence vaccinators recommendation practice. Economic incentives prompted health professionals to recommend non-scheduled vaccines; however, the application of such staff incentives varied widely in China. To adopt appropriate economic incentives, professional organizations should develop protocols for the use of incentives that account for their influence on recommendation practices. Suitable recommendation policy needs to balance basic salaries with performance-based incentives, consider overall workload, and include monitoring and evaluation of economic incentives.

Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3–4 weeks before onset of vaccine meningitis may be a risk factor in some cases.

Varicella-Zoster Virus (Varicella and Shingles)

A live attenuated vaccine against varicella (later also used to prevent zoster) was developed in 1974 by Takahashi and colleagues. Varicella vaccine was licensed for universal immunization of healthy children in the United States in 1995. It is also now used for this purpose in at least 15 additional countries all over the world. Varicella is disappearing in the US. Varicella vaccine has proven extremely safe and side effects are unusual, mild, and less serious than varicella or its complications. 85% of children are protected completely after 1 dose; the 15% who develop varicella despite immunization usually (but not always) have mild infections. These 15%, however, can transmit the wild type virus to others. Therefore, for optimal effect, 2 doses are required, mostly to address children who did not have an optimal primary immune response after the first dose. Waning immunity does not seem to pose a serious problem, but surveillance of vaccinees is continuing. It was demonstrated in 2005 that at a high dose of vaccine – 15 times higher than that used for prevention of varicella in children - zoster in adults can also be safely prevented. The live attenuated zoster vaccine is effective in approximately 50% of healthy individuals over age 60 who have had varicella in the past, and therefore have latent infection with varicella-zoster virus. It is given as one dose, but its effect runs out about 8 years after vaccination. In 2017, a new vaccine against zoster was also introduced. This is a subunit vaccine which does not contain contagious virus. It is even more effective than the older zoster vaccine and is over 95% effective in adults 50–≥70 years of age in preventing zoster and post herpetic neuralgia.

Parental acceptance and knowledge of varicella vaccination in relation to socioeconomics in Sweden: A cross-sectional study

Varicella infection is a highly contagious disease which, whilst mild in most cases, can cause severe complications. Varicella vaccination is available privately in Sweden and is currently being reviewed for inclusion in the Swedish Public Health Agency’s national immunisation program (NIP). A cross-sectional study of parents of Swedish children aged 1–8 years (n = 2212) was conducted to understand parental acceptance, beliefs and knowledge around varicella infection and vaccination. Respondents generally viewed varicella infection as a mild disease, with only a small proportion aware of potential severe complications. While 65% of respondents were aware of the vaccine, only 15% had started the course of vaccination as of February 2019. Further, 43% of parents did not intend to vaccinate, most commonly due to lack of inclusion in the NIP, but also due to perception of mild disease. Nevertheless, if offered within the NIP, 85% of parents would be highly likely to vaccinate their child. A number of statistically significant differences in awareness and behaviours were observed between sociodemographic subgroups. In general, women were more aware of vaccination (72%) compared to men (58%). Among unemployed or respondents with elementary school education, awareness was below 43%, and among respondents with high income the awareness was above 75%. Similarly, among unemployed or respondents with a low income the vaccination rate was as low as 30% compared with at least 57% among respondents with a high income. Respondents from metropolitan areas, those with university degrees and respondents with a higher income were more likely to be aware of the varicella vaccine and to have vaccinated their child. Whilst inclusion in the NIP is clearly the main driver for uptake, these identified knowledge gaps should inform educational efforts to ensure that all parents are informed of the availability and benefits of the varicella vaccine independent of socioeconomic status.

Catch-up immunization for adolescents and young adults during pre-travel consultation in Japan

Rubella and measles outbreaks in adults occur because of unimmunized or partially immunized status. Travel clinics play an important role in catch-up measles, rubella, mumps, and varicella immunization for adults. We evaluated the need for catch-up measles, rubella, mumps, and varicella immunization by young adults at our travel clinic. This retrospective observational study was conducted at the National Center for Global Health and Medicine from June 1, 2017 to May 31, 2018. Adults aged 16–49 years who received pre-travel consultation and had childhood immunization records were included. Individuals who fully or partially received planned measles, rubella, mumps, and varicella catch-up immunization were classified as “immunized.” We calculated the proportion of “immunized” individuals and analyzed the factors associated with catch-up measles, rubella, mumps, and varicella immunization at pre-travel consultation using logistic regression analysis. Overall, 3,456 individuals received pre-travel consultations during the study period; 827 (336 men, median age 22 years) had childhood immunization records. The most common trip purposes were study (33%) and tourism (24%). The most common destination was Asia (39%). Catch-up immunization of any measles, rubella, mumps, and varicella vaccine was needed by 755 individuals. After consultation, 20–46% of these participants who needed catchup immunization received at least one dose of immunization. Factors that are negatively associated with measles, rubella, mumps, and varicella catch-up immunization were tourism (odds ratio 0.37 to 0.58), yellow fever vaccination (0.45 to 0.50) (excluding varicella), and each disease history (0.13 to 0.40) (excluding rubella and varicella). Further studies are needed to identify barriers to catch-up immunization.

Nectin-1 is an entry mediator for VZV infection of human neurons

Varicella zoster virus (VZV) maintains lifelong latency in neurons following initial infection and can subsequently be reactivated to result in herpes zoster or severe neurological manifestations such as encephalitis. Mechanisms of VZV neuropathogenesis have been challenging to study due to the strict human tropism of the virus. While neuronal entry mediators of other herpesviruses, including herpes simplex virus, have been identified, little is known regarding how VZV enters neurons. Here, we utilize a human stem cell based neuronal model to characterize cellular factors that mediate entry. Through transcriptional profiling of infected cells, we identify the cell adhesion molecule nectin-1 as a candidate mediator of VZV entry. Nectin-1 is highly expressed in the cell bodies and axons of neurons. Either knockdown of endogenous nectin-1 or incubation with soluble forms of nectin-1 produced in mammalian cells results in a marked decrease in infectivity of neurons. Notably, while addition of soluble nectin-1 during viral infection inhibits infectivity, addition after infection has no effect on infectivity. Ectopic expression of human nectin-1 in a cell line resistant to productive VZV infection confers susceptibility to infection. In summary, we have identified nectin-1 as a neuronal entry mediator of VZV. IMPORTANCE Varicella zoster virus (VZV) causes chickenpox, gains access to neurons during primary infection where it resides lifelong, and can later be reactivated. Reactivation is associated with shingles and postherpetic neuralgia, as well as with severe neurologic complications including vasculitis and encephalitis. Although the varicella vaccine substantially decreases morbidity and mortality associated with primary infection, the vaccine cannot prevent development of neuronal latency and vaccinated populations are still at risk for reactivation. Furthermore, immunocompromised individuals are at higher risk for VZV reactivation and associated complications. Little is known regarding how VZV enters neurons. Here, we identify nectin-1 as an entry mediator of VZV in human neurons. Identification of nectin-1 as a neuronal VZV entry mediator could lead to improved treatments and preventative measures to reduce VZV related morbidity and mortality.