Sufficient reproduction numbers to prevent recurrent epidemics (preprint)

Current practice in the design and evaluation of epidemic control measures, including vaccination, is largely based on reproduction numbers (RNs), which represent prognostic indexes of long-term disease transmission, both in naive populations (basic RN) and in the presence of prior exposure or interventions (effective RN). A standard control objective is to establish herd immunity, e.g., by immunizing enough susceptible individuals to achieve RN<1. However, attaining this goal is not sufficient to avoid transient outbreaks that, in the short term, might revamp epidemics by coalescence of subthreshold flare-ups. Using reactivity analysis applied to a discrete SIR model with age-of-infection structure, we determine sufficient conditions to prevent transient epidemic dynamics and recurrent, non-periodic outbreaks due to imported cases. These conditions are based on fundamental infection characteristics, namely the average infectiousness clearance rate, the generation time distribution, and the RN. We show that preventing subthreshold epidemicity requires stricter RN thresholds than simply maintaining RN<1. Taking into account a wide spectrum of respiratory viral infections, epidemicity-curbing RN thresholds vary between 0.10 (rubella) and 0.51 (MERS), with a median of 0.26 close to the estimate of 0.24 for the ancestral SARS-CoV-2 virus. The portion of the population that needs to be included in containment efforts to avoid short-term outbreaks is considerably higher than herd immunity thresholds (HITs) based solely on the basic RN (e.g., 93% vs. 72% for ancestral SARS-CoV-2). We also find that subthreshold epidemicity is harder to prevent for pathogens with a longer mean generation time, smaller standard deviation of the generation time distribution, longer duration of infection, and higher RN. Determining sufficient RN thresholds to prevent transient outbreaks is a key challenge in disease ecology, with practical consequences for the design of control measures, as the weaker RN reductions and HITs associated with customary control targets may prove ineffective in preventing potentially recurrent flare-ups. Due to its modest data requirements, our modeling framework may also have important implications for human and non-human diseases caused by emerging pathogens.

A Four Years Longitudinal Study of Childhood Vaccination Trends and Supply Chain Resilience in Tanzania amid COVID-19 Pandemic (preprint)

Background The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services such as childhood immunisations. This study delves into the impact of these disruptions on routine childhood vaccination programs in Tanzania. Methodology We conducted a longitudinal study over four years in five Tanzanian regions: Mwanza, Dar es Salaam, Mtwara, Arusha, and Dodoma. The study analysed trends in the usage of six key vaccines: Bacille Calmette-Guérin (BCG), Bivalent Oral Polio Vaccine (bOPV), Diphtheria Tetanus Pertussis, Hepatitis-B and Hib vaccine (DTP-HepB-Hib), measles-rubella (MR), Pneumococcal Conjugate Vaccine (PCV), and Rota vaccines. We evaluated annual and monthly vaccination trends using time series and regression analyses. Predictive modelling was performed using an Autoregressive Integrated Moving Average (ARIMA) model. Results The study recorded a total of 32,602,734 vaccination events across the regions from 2019 to 2022. Despite declining vaccination rates in 2020, there was a notable rebound in 2021, indicating the resilience of Tanzania's immunisation program. The analysis also highlighted regional differences in varying vaccination rates when standardised per 1000 population. Seasonal fluctuations were observed in the monthly vaccination rates, with BCG showing the most stable trend. Predictive modelling of BCG indicated stable and increasing vaccination coverage through 2023. Conclusion The findings underscore the robustness of Tanzania's childhood immunisation infrastructure in overcoming the challenges posed by the COVID-19 pandemic, marked by a strong recovery in vaccination rates post-2020. We provide valuable insights into the dynamics of vaccinations during a global health crisis and highlight the importance of sustained immunisation efforts in maintaining public health.

Implementation of the preventive vaccination program in the time of the COVID-19 pandemic - single center study.

INTRODUCTION: In addition to many diagnostic and therapeutic procedures, the COVID-19 pandemic also limited prophylaxis, including the implementation of the vaccination program among children. OBJECTIVE: The aim of the study was to assess the implementation of the vaccination program in the area covered by the care of patients of a selected Primary Health Care clinic in the city of Krakow in the field of selected vaccinations during the COVID-19 pandemic. MATERIAL AND METHODS: A retrospective study based on secondary data was conducted in a selected clinic (Kraków, Poland) that cares for 1,982 children aged 0-19 years. An analysis of the vaccination coverage in selected groups of children in 2019, 2020 and 2021 was carried out based on annual reports (MZ-54). Vaccination coverage against: diphtheria, tetanus, whooping cough, measles, mumps, rubella, influenza and pneumococcal infection was analyzed. The collected data were analyzed using descriptive statistics, Chi2 test and Fisher's exact test. RESULTS: In the general vaccination status of two-year-olds, no significant differences were observed in the period 2019-2021 (p=0.156). The percentage of fully vaccinated increased from 77.6% in 2019, to 81.5% in 2020 and to 85.2% in 2021. However, a high rate of vaccination refusals was observed in 2021 (4.1%) in this group. The percentage of 2-year-olds vaccinated against pneumococci (PCV) and 3-year-olds against diphtheria, tetanus, pertussis (DTP), and measles, mumps, rubella (MMR) in the years 2019-2021 was increasing. For DTP and MMR, this increase was significant (p<0.05). In the group of older children, in 2020 the percentage of 7- and 15-year-olds vaccinated decreased compared to 2019 and 2021, but the difference was insignificant (p>0.05). A significant difference in vaccination coverage was observed in the group of 19-year-olds, in which in 2020 the percentage of vaccinated was 58% (in 2019 - 74.6%, in 2021 - 81%). The largest number of children under the age of 5 were vaccinated against influenza in 2021, but it was only less than 2% of this group. CONCLUSIONS: Sanitary restrictions introduced during the COVID-19 pandemic did not significantly affect the vaccination status of children in selected age groups against the analyzed vaccine-preventable diseases. The exception is the group of 19-year-olds, whose vaccination coverage in 2020 was much lower than in 2019 and 2021. In addition, an increase in refusals of vaccination was observed, reaching 4.1% in 2021 in the group of the youngest patients.

Dissecting Rubella Placental Infection in an In Vitro Trophoblast Model.

Vertical transmission of rubella virus (RuV) occurs at a high rate during the first trimester of pregnancy. The modes of vertical transmission including the response of trophoblasts to RuV are not well understood. Here, RuV-trophoblast interaction was studied in the BeWo trophoblast cell line. Analysis included early and late time-point kinetics of virus infection rate and the antiviral innate immune response at mRNA and protein level. BeWo characteristics were addressed through metabolic activity by extracellular flux analysis and syncytiotrophoblast formation through incubation with forskolin. We found that RuV infection of BeWo led to profuse type III interferon (IFN) production. Transfecting trophoblast cells with dsRNA analog induced an increase in the production of type I IFN-ß and type III IFNs; however, this did not occur in RuV-infected BeWo trophoblasts. IFN-ß and to a lesser extent type III IFN-λ1 were inhibitory to RuV. While no significant metabolic alteration was detected, RuV infection reduced the cell number in the monolayer culture in comparison to the mock control and resulted in detached and floating cells. Syncytia formation restricted RuV infection. The use of BeWo as a relevant cell culture model for infection of trophoblasts highlights cytopathogenicity in the absence of a type I IFN response as a pathogenic alteration by RuV.

Changes in vaccination administration in Japan.

This paper reviews the administration related to vaccination in Japan after the enactment of the Immunization Act in 1948, under which vaccination was implemented mandatory for the public. To enhance the effectiveness of vaccination activities, the government implemented group vaccination, which is convenient for vaccinating recipients all at once. In 1976, Japan established the relief system for health damage after vaccination. While some projects, such as the mass administration of live oral polio vaccine in 1961, achieved excellent results, incidents leading to health damage occurred, such as the diphtheria toxoid immunization incident (1948) and frequent occurrence of aseptic meningitis owing to the measles, mumps, and rubella vaccine (1989). In December 1992, the Tokyo High Court sentenced that the onset of health damage after vaccination could be attributed to the negligence of the national government. In the revision of the Immunization Act in 1994, the "mandatory vaccination" enforced until then was changed to "recommended vaccination." The Act was also changed to recommend "individual vaccination" in principle, which is performed after primary care physicians investigate the physical condition of individual recipients and carefully conduct preliminary examination. For approximately 20 years from the 1990s, a vaccine gap existed between Japan and other countries. From around 2010, efforts have been made to bridge this gap and establish the global standard in vaccination.

[Quality analysis of a combined domestic vaccine for the prevention of measles, rubella and mumps].

INTRODUCTION: The need to maintain a high level of vaccination coverage against measles, rubella and mumps in conditions of an increased risk of outbreaks of infections due to violations of vaccination tactics associated with the pandemic of coronavirus infection and due to the unfavorable epidemic situation in neighboring countries determines the advisability of using a combined vaccine for the simultaneous prevention of these three socially significant infections. THE AIM OF THE STUDY: to analyze the quality of commercial series of a new domestic combined cultured live vaccine against measles, rubella and mumps (MRM) throughout the entire time of its manufacturing according to all specification indicators in regulatory documentation (RD). MATERIALS AND METHODS: The object of the study was the combined cultured live vaccine against measles, rubella and mumps. The analysis of the quality of the drug was carried out according to 86 consolidated production protocols of manufactured series, as well as according to the results of control of these series in the Testing Center for Quality Expertise of the Federal State Budgetary Institution NCESMP of the Ministry of Health of the Russian Federation. RESULTS: It is shown that the quality of the combined drug for the prevention of measles, rubella and mumps corresponds to the RD in all studied indicators. The drug does not contain an antibiotic. Bovine serum albumin, which is a technological impurity, is detected in quantities more than 5 times lower than the established norm. A comparison of the specific activity of the viral components of new combined domestic vaccine and the components of the bivalent vaccine against measles and mumps produced by the company in 20192021 showed that the spread of the activity values of the viral components in the new drug and in the series of mumps-measles vaccine was minimal, which allowed us to make a conclusion about the stability of the production technology. CONCLUSION: The quality of the new domestic combined vaccine for the prevention of measles, rubella and mumps meets WHO requirements. The results of the conducted studies indicate the stability of production and the standard quality of the drug. The use of a combined vaccine against three significant infections will ensure the necessary level of vaccination coverage in the population. Information about the results of studies can help reduce the number of vaccination refusal.

Family Physicians Can/Should Do: What? Where? And How?

This issue's teasers: A broad scope of care by family physicians could be incentivized and has positive outcomes. Family physicians could do more dermoscopy-a mixed specialty group of experts provide information on diagnosis with associated features and proficiency standards for primary care clinicians. Clinicians could trust more, and do less, such as adult measles-mumps-rubella boosters. Family physicians differ from pediatricians on how to deliver vitamin D to newborns. Practice scope varies by location. Is monetary incentive a key to incentivize COVID vaccination? A new, useful, easy functional status questionnaire. This issue also includes articles on both adult and pediatric obesity, a systematic review of social determinants of health and documentation thereof, plus more.

Low-Dose Interferon I and III-Based Nasal Sprays: A Good-Looking COVID-19 Vaccine Candidate and a Therapy of the Future? (preprint)

The SARS–CoV-2 infection has caused both acute and chronic COVID–19 disease during the recent pandemic with emerging more transmissible SARS–CoV–2 Omicron variants (BQ1 and XBB1) that have increased demands for more effective immunogens and therapeutic approaches to protect the lives of numerous SARS–CoV-2 affected individuals and reduce overall disease burden that could be affected by concurrent other pathogens causing diseases. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of novel SARS–CoV–2 infections due to higher mutation rates within specific areas of the SARS–CoV-2 domain, leading to enhanced viral entry, especially within individuals with one or more significant comorbidities, and there is still a dilemma of how prevention of future pandemics will occur as within host animal mutations and cross species transfer naturally occurs. Concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to remain undetected during the first stages of infection by means of capping the 5' end of their DNA and RNA genes respectively. This may occur by reducing the rate of host Type I and Type III Interferons (IFN) cellular synthesis, that would usually occur and affect both apoptotic pathways, that facilitate viral replication and clearance, as well as immune cells, that process and present pathogenic antigen epitopes. Furthermore, although methods of vaccination exist, other methods in clinical development remain that could evoke an immune response in different cellular, serum or mucosal compartments being cellular, serum and mucosal that evoke differential antibody responses. Antibodies are classed as natural and synthetic. Natural antibodies are further classified into neutralizing and non-neutralizing, whilst synthetic antibodies are also further classified into monoclonal and polyclonal. As a result of single cell study transcriptome research, viruses do utilize an array of protein receptors for receptor-mediated cellular entry. This, therefore suggests that potential differential production of antibody immunoglobulins (Ig) within serum and mucosal areas remains affected by cytokines, adhesion molecules and chemokines that can be upregulated or downregulated upon host viral infection. Serum plasma antibodies can be multimeric that may not efficiently cross the nasal epithelium cell layer, therefore offering less protection against mucosal inflammation due to mucin proteins. On the other hand, antibodies produced by mucosal plasma cells at epithelial surfaces are known to provide effective immune responses in some viral infections. The existence of developments that stimulate mucosal immune responses has so far only been seen with influenza nasal immunogens. Nevertheless, scientists developed ways of immunization and early treatment worldwide that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration. For example, the administration of human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can stimulate cellular activity to train the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses through genetic recombination pose challenges to traditional concepts of cellular and molecular immune system neutralization of these viruses during the first stages of cellular infection. It is until the scientific community realizes this potentially crucial aspect that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently monkeypox. Type I IFNs tend to be produced faster than Type III IFNs, and the first induce slightly more abundant pro-inflammatory signals than the latter, meaning that type III IFNs, if produced early, may further decrease the extent of excessive proinflammatory signals. Hence, we believe that nasal sprays containing a low dosage of Type I and Type III IFNs not only represent a relevant COVID-19 therapeutic, but also a potential unknown modulatory therapy of the future. Of note, it has been indicated that IFN I and / or III display significant immunizing and early therapeutic effects for other viral evoked diseases like Influenza (Influenza (A)H1N1), rabies (Rabies lyssavirus), measles (Measles virus), rubella (Rubivirus rubellae), Hepatitis B, HIV-induced AIDS, Ebola, Marburg, as well as bacterial diseases, such as lower respiratory tract infectious diseases induced by Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus, and a number of oncological diseases, like hepatic melanoma.

Past as Prologue-Use of Rubella Vaccination Program Lessons to Inform COVID-19 Vaccination.

The rapid rollout of vaccines against COVID-19 as a key mitigation strategy to end the global pandemic might be informed by lessons learned from rubella vaccine implementation in response to the global rubella epidemic of 1963-1965. That rubella epidemic led to the development of a rubella vaccine that has been introduced in all but 21 countries worldwide and has led to elimination of rubella in 93 countries. Although widespread introduction and use of rubella vaccines was slower than that for COVID-19 vaccines, the process can provide valuable insights for the continued battle against COVID-19. Experiences from the rubella disease control program highlight the critical and evolving elements of a vaccination program, including clearly delineated goals and strategies, regular data-driven revisions to the program based on disease and vaccine safety surveillance, and evaluations to identify the vaccine most capable of achieving disease control targets.

Implementation of a quality improvement programme using the Active Patient Link call and recall system to improve timeliness and equity of childhood vaccinations: protocol for a mixed-methods evaluation.

INTRODUCTION: Call and recall systems provide actionable intelligence to improve equity and timeliness of childhood vaccinations, which have been disrupted during the COVID-19 pandemic. We will evaluate the effectiveness, fidelity and sustainability of a data-enabled quality improvement programme delivered in primary care using an Active Patient Link Immunisation (APL-Imms) call and recall system to improve timeliness and equity of uptake in a multiethnic disadvantaged urban population. We will use qualitative methods to evaluate programme delivery, focusing on uptake and use, implementation barriers and service improvements for clinical and non-clinical primary care staff, its fidelity and sustainability. METHODS AND ANALYSIS: This is a mixed-methods observational study in 284 general practices in north east London (NEL). The target population will be preschool-aged children eligible to receive diphtheria, tetanus and pertussis (DTaP) or measles, mumps and rubella (MMR) vaccinations and registered with an NEL general practice. The intervention comprises an in-practice call and recall tool, facilitation and training, and financial incentives. The quantitative evaluation will include interrupted time Series analyses and Slope Index of Inequality. The primary outcomes will be the proportion of children receiving at least one dose of a DTaP-containing or MMR vaccination defined, respectively, as administered between age 6 weeks and 6 months or between 12 and 18 months of age. The qualitative evaluation will involve a 'Think Aloud' method and semistructured interviews of stakeholders to assess impact, fidelity and sustainability of the APL-Imms tool, and fidelity of the implementation by facilitators. ETHICS AND DISSEMINATION: The research team has been granted permission from data controllers in participating practices to use deidentified data for audit purposes. As findings will be specific to the local context, research ethics approval is not required. Results will be disseminated in a peer-reviewed journal and to stakeholders, including parents, health providers and commissioners.

Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

INTRODUCTION: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. METHODS: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. RESULTS: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). DISCUSSION: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Emerging Methods in Biosensing of Immunoglobin G-A Review.

Human antibodies are produced due to the activation of immune system components upon exposure to an external agent or antigen. Human antibody G, or immunoglobin G (IgG), accounts for 75% of total serum antibody content. IgG controls several infections by eradicating disease-causing pathogens from the body through complementary interactions with toxins. Additionally, IgG is an important diagnostic tool for certain pathological conditions, such as autoimmune hepatitis, hepatitis B virus (HBV), chickenpox and MMR (measles, mumps, and rubella), and coronavirus-induced disease 19 (COVID-19). As an important biomarker, IgG has sparked interest in conducting research to produce robust, sensitive, selective, and economical biosensors for its detection. To date, researchers have used different strategies and explored various materials from macro- to nanoscale to be used in IgG biosensing. In this review, emerging biosensors for IgG detection have been reviewed along with their detection limits, especially electrochemical biosensors that, when coupled with nanomaterials, can help to achieve the characteristics of a reliable IgG biosensor. Furthermore, this review can assist scientists in developing strategies for future research not only for IgG biosensors but also for the development of other biosensing systems for diverse targets.

Vaccine Preventable Disease Seroprevalence In a Nationwide Assessment of Timor-Leste (VASINA-TL) - study protocol for a population-representative cross-sectional serosurvey (preprint)

Introduction: Historic disruption in health infrastructure combined with data from a recent vaccine coverage survey suggests there are likely significant immunity gaps to vaccine preventable diseases and high risk of outbreaks in Timor-Leste. Community-based serological surveillance is an important tool to augment understanding of population-level immunity achieved through vaccine coverage and/or derived from prior infection. Methods and analysis: This national population-representative serosurvey will take a three-stage cluster sample and aims to include 5600 individuals above one year of age. Serum samples will be collected by phlebotomy and analysed for measles immunoglobulin G (IgG), rubella IgG, severe acute respiratory syndrome coronavirus-2 anti-spike protein IgG, hepatitis B surface antibody and hepatitis B core antigen using commercially available chemiluminescent immunoassays or enzyme-linked immunosorbent assays. In addition to crude prevalence estimates and to account for differences in Timor-Leste age structure, we will calculate stratified age-standardised prevalence estimates, using Asia in 2013 as the standard population. Additionally, this survey will derive a national asset of serum and dried blood spot samples which can be used for further investigation of infectious disease sero-epidemiology and/or validation of existing and novel serological assays for infectious diseases. Ethics and dissemination: Ethical approval has been obtained from the Research Ethics and Technical Committee of the Instituto Nacional da Saude,Timor-Leste and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research, Australia. Co-designing this study with Timor-Leste Ministry-of-Health and other relevant partner organisations will allow immediate translation of findings into public health policy (which may include changes to routine immunisation service delivery and/or plans for supplementary immunisation activities).

Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.

OBJECTIVES: To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination. DESIGN: Longitudinal study using primary care electronic health records. SETTING: 285 general practices in North East London. PARTICIPANTS: Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort). MAIN OUTCOME MEASURE: Receipt of timely MMR vaccination between 12 and 18 months of age. METHODS: We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations. RESULTS: Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic. CONCLUSIONS: The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.

Epidemiological features and risk factors for measles and rubella in Taiwan during 2011 to 2020.

The risk of geographic transmission of infectious diseases due to air travel varies greatly. Our aim is to survey empirical data that provide a retrospective historical perspective on measles and rubella. This study used the open data website provided by the Taiwan Centers for Disease Control (TCDC) to extract the reported numbers of measles and rubella case between 2011 and 2020. There were 306 cases of measles and 135 cases of rubella. The incidence of measles and rubella per million population were 0 to 6.0 and 0 to 2.6, respectively. There was a gradual increase in the numbers of cases in those aged 20-39 years, and distinct duration patterns. It indicated that the risk of contracting rubella has significantly decreased in the last 5 years. Measles cases aged 20 to 39 years accounted for 72.5% of all cases. Rubella cases aged 20 to 39 years accounted for 59.3% of all cases. The male and residency in the Taipei metropolitan area or northern area were identified as potential risk factors for measles and rubella. Coverage with the first dose of the measles, mumps and rubella (MMR) vaccine in Taiwan increased from 97.31% to 98.86%, and the uptake rate of the second dose of the MMR vaccine increased from 95.73% to 98.39% between 2010 and 2020. Furthermore, the numbers of imported cases of measles (n = 0) and rubella (n = 0) reported during the coronavirus disease 2019 (COVID-19) pandemic were lower than those from 2011 to 2019. Measles and rubella cases were imported most frequently from Cambodia and Vietnam. This study represents the first report of confirmed cases of acquired measles and rubella from surveillance data of the TCDC between 2011 and 2020, also demonstrates that the numbers of cases of measles and rubella significantly decreased in Taiwan during the COVID-19 pandemic.

Acceptability of serosurveys in southern Zambia: surveyor and community perspectives (preprint)

Background: Factors associated with whether individuals choose to participate in serosurveys  are not well understood. Understanding perceptions from multiple perspectives, including the perspectives of both data collectors and participants through a holistic model such as the socio-ecological model contextualizes individual, interpersonal, and structural level influences on survey research participation. We used a multiple methods approach to characterize reasons for serosurvey participation in communities in Southern Province, Zambia where a serosurvey was conducted in 2016. Methods: The first phase conducted focus group discussions and in-depth interviews with 24 data collectors who participated in a measles-rubella serosurvey in 2016. The second phase surveyed 34 caregivers at health facilities to identify barriers and facilitators to serosurvey participation. Emergent themes were then classified into a socio-ecological model using individual, interpersonal, and structural level constructs. Results: Common themes emerged from data collectors as well as caregivers surveyed. At the individual level, providing incentives was a motivator, and some religious beliefs were described as a barrier to serosurvey participation. At the interpersonal level, family dynamics and community influences could help or hinder serosurvey participation.  Community health workers were consistently named as facilitators of participation. At the structural level, concerns about specimen collection, who was selected for serosurveys, and not receiving test results arose as potential barriers. The most frequently reported facilitator was provision of information about the purpose of the serosurvey (85% of respondents). The most frequently reported barrier was lack of clarity regarding use of their blood specimen (53% of respondents). For specimen collection type, caregivers consistently preferred finger prick blood collection over both venous blood draw and oral swabs. Conclusion: Serosurvey participation was deemed acceptable to most study participants. The socioecological model revealed barriers and facilitators for participation to guide strategies to improve participation which can be applied to ongoing serosurveys for SARS-CoV-2. Serosurveys should develop an engagement plan to provide information about blood collection ahead of the serosurvey and communicate the objectives of the study through a trusted source such as community health workers.

THE EFFECT OF THE MEASLES, MUMPS AND RUBELLA VACCINE ON INNATE AND ADAPTIVE IMMUNE RESPONSES IN PERSONS RECEIVING A SARS-COV-2 mRNA VACCINE.A SUB-STUDY OF THE CROWN CORONATION TRIAL (preprint)

ABSTRACT Vaccination elicits a complex combination of immune responses. Immune memory formation is observed not only in the antibody responses of B-cells, but also in the T-cell response. Moreover, some live attenuated vaccines such as measles-containing vaccines can induces heterologous protection, likely through induction of memory characteristics in the innate immune response. Little is known about the immunological interaction that may occur when different vaccines are administered soon after one another, especially in relation to the novel COVID-19 vaccines. The aim of this study was to compare the innate and adaptive immune responses between persons randomized to receive either a MMR or a placebo (0.9% NaCl) injection prior to their SARS-CoV-2 mRNA vaccination. We compared: i) the cytokine and chemokine production (tumor necrosis factor [TNF]-, interleukin [IL]-1{beta}, IL-6, IL-10, IL-17, IL-22, interferon [IFN]- and IFN-{gamma}) after in-vitro stimulation of peripheral blood mononuclear cells (PBMCs) with heterologous stimuli (severe acute respiratory syndrome coronavirus [SARS-CoV]-2, measles mumps and rubella [MMR] vaccine, Toll-like receptor [TLR]-3 ligand, TLR-7/8 ligand, or TLR-4 ligand), and ii) the SARS-CoV-2 neutralizing antibody responses. Ninety-five participants in the CROWN CORONATION trial (NCT04333732; a randomized control trial comparing MMR to placebo for prevention of COVID-19) agreed to an additional single blood sample collection for this immunological study. Samples were collected around 196 (SD 22) days after administration of MMR or placebo, and around 105 (SD 27) days after their second SARS-CoV-2 mRNA vaccine injection. Twenty-four percent of participants were older than fifty and sixty-seven percent were female. The median TNF- response to stimulation with MMR was 8315.3 pg/mL in the MMR group and 4340.5 pg/mL in the placebo group; adjusted median difference (95% CI) 3012.5 (-4734.1; -323.5); p=0.017. No other significant differences were noted in the cytokine and chemokine responses between treatment groups. The SARS-CoV-2 neutralization assay geometric mean (SD) IC50 in the MMR group was 507.6 (2.6) and in the placebo group was 515.7 (2.2); ratio of geometric means (95% CI) 1.0 (0.7; 1.5). Pre-exposure to MMR vaccine was generally not associated with changes in cytokine and chemokine responses of stimulated PBMCs at 105 (27) days after SARS-CoV-2 mRNA vaccination. MMR vaccination led only to an increase of TNF- production in response to an additional ex-vivo stimulation with the MMR vaccine. The SARS-CoV-2 neutralization IC50 values did not differ between MMR and placebo groups. Further studies using a repeated measures design would be better suited to explore or rule-out any short-lived vaccine response and vaccine-vaccine immunological interaction.