Nasal and pharyngeal mucosal immunity to poliovirus in children following routine immunization with inactivated polio vaccine (IPV) in the United States of America.

BACKGROUND: Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine-induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool. METHODS: To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2 to 5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs. RESULTS: PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received four IPV doses. Across the three PV serotypes, both nasal (Spearman's rho ≥ 0.87, p≤0.0003 for all) and adenoid (Spearman's rho ≥0.57, p≤0.05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization. CONCLUSIONS: Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine-induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity.

A SARS-CoV-2 outbreak in a plastics manufacturing plant.

BACKGROUND: A SARS-CoV-2 outbreak with an attack rate of 14.3% was reported at a plastics manufacturing plant in England. METHODS: Between 23rd March and 13th May 2021, the COVID-OUT team undertook a comprehensive outbreak investigation, including environmental assessment, surface sampling, molecular and serological testing, and detailed questionnaires, to identify potential SARS-CoV-2 transmission routes, and workplace- and worker-related risk factors. RESULTS: While ventilation, indicated using real-time CO2 proxy measures, was generally adequate on-site, the technical office with the highest localized attack rate (21.4%) frequently reached peaks in CO2 of 2100ppm. SARS-CoV-2 RNA was found in low levels (Ct ≥35) in surface samples collected across the site. High noise levels (79dB) were recorded in the main production area, and study participants reported having close work contacts (73.1%) and sharing tools (75.5%). Only 20.0% of participants reported using a surgical mask and/or FFP2/FFP3 respirator at least half the time and 71.0% expressed concerns regarding potential pay decreases and/or unemployment due to self-isolation or workplace closure. CONCLUSIONS: The findings reinforce the importance of enhanced infection control measures in manufacturing sectors, including improved ventilation with possible consideration of CO2 monitoring, utilising air cleaning interventions in enclosed environments, and provision of good-quality face masks (i.e., surgical masks or FFP2/FFP3 respirators) especially when social distancing cannot be maintained. Further research on the impacts of job security-related concerns is warranted.

Chemical Attenuation in the Development of a Whole-Organism Malaria Vaccine.

Malaria vaccine development has been dominated by the subunit approach; however, many subunit vaccine candidates have had limited efficacy in settings of malaria endemicity. As our search for an efficacious malaria vaccine continues, the development of a whole-organism vaccine is now receiving much scrutiny. One strategy currently being explored in the development of a whole-organism vaccine involves chemical attenuation of the malaria parasite. In vivo and in vitro chemical attenuation of both liver-stage and blood-stage Plasmodium parasites has been investigated. Here, we discuss both approaches of chemical attenuation in the development of a whole-organism vaccine against malaria.

Chemically Attenuated Blood-Stage Plasmodium yoelii Parasites Induce Long-Lived and Strain-Transcending Protection.

The development of a vaccine is essential for the elimination of malaria. However, despite many years of effort, a successful vaccine has not been achieved. Most subunit vaccine candidates tested in clinical trials have provided limited efficacy, and thus attenuated whole-parasite vaccines are now receiving close scrutiny. Here, we test chemically attenuated Plasmodium yoelii 17X and demonstrate significant protection following homologous and heterologous blood-stage challenge. Protection against blood-stage infection persisted for at least 9 months. Activation of both CD4(+) and CD8(+) T cells was shown after vaccination; however, in vivo studies demonstrated a pivotal role for both CD4(+) T cells and B cells since the absence of either cell type led to loss of vaccine-induced protection. In spite of significant activation of circulating CD8(+) T cells, liver-stage immunity was not evident. Neither did vaccine-induced CD8(+) T cells contribute to blood-stage protection; rather, these cells contributed to pathogenesis, since all vaccinated mice depleted of both CD4(+) and CD8(+) T cells survived a challenge infection. This study provides critical insight into whole-parasite vaccine-induced immunity and strong support for testing whole-parasite vaccines in humans.

A SARS-CoV-2 outbreak investigation at a storage and distribution centre in England: an assessment of worker- and workplace-related risk factors.

An outbreak of SARS-CoV-2 (1 March to 10 May 2021) with an attack rate of 26.5% among approximately 1150 workers at a storage and distribution centre in England prompted a multidisciplinary outbreak investigation (5 May to 6 August 2021), with the aim of better understanding worker- and workplace-related risk factors for viral transmission in the warehousing sector. Overall, environmental factors (e.g., ventilation, humidity and temperature) were assessed to be appropriate at the facility. Nevertheless, 39 (51.3%) surface samples from across the site tested positive for low/ very low levels of SARS-CoV-2 RNA (Ct value ≥ 32.0 for all). Among the study participants, of whom 35.6% were confirmed or suspected cases, 95.5% reported having received COVID-19 prevention training, 100.0% reported handwashing, and 80.0% reported use of face coverings at work. Notably, 43.9% and 19.0% reported working with a symptomatic and a positive contact respectively. Furthermore, 80.5% and 46.3% had concerns regarding reduction in their income and future unemployment, respectively, due to self-isolation. The findings of this study suggest that, in addition to targeted workplace infection control measures and tailored work area specific risk assessments, an enhanced and equitable sick leave policy may help limit presenteeism and viral transmission in large workplaces.

A SARS-CoV-2 outbreak in a public order and safety training facility in England, June 2021.

BACKGROUND: The public order and safety (POS) sector remains susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks, as workplace attendance is typically compulsory and close physical contact is often needed. Here, we report on a SARS-CoV-2 outbreak with an attack rate of 39% (9/23), which occurred between 19 and 29 June 2021 among a cohort of new POS recruits participating in a mandatory 18-week training programme in England. METHODS: The COVID-OUT (COVID-19 Outbreak investigation to Understand Transmission) study team undertook a multidisciplinary outbreak investigation, including viral surface sampling, workplace environmental assessment, participant viral and antibody testing, and questionnaires, at the two associated training facilities between 5 July and 24 August 2021. RESULTS: Environmental factors, such as ventilation, were deemed inadequate in some areas of the workplace, with carbon dioxide (CO2) levels exceeding 1,500 ppm on multiple occasions within naturally ventilated classrooms. Activities during safety training required close contact, with some necessitating physical contact, physical exertion, and shouting. Furthermore, most participants reported having physical contact with colleagues (67%) and more than one close work contact daily (97%). CONCLUSIONS: Our investigation suggests that site- and activity-specific factors likely contributed to the transmission risks within the POS trainee cohort. Potential interventions for mitigating SARS-CoV-2 transmission in this POS training context could include implementing regular rapid lateral flow testing, optimizing natural ventilation, using portable air cleaning devices in classrooms, and expanding use of well-fitted FFP2/FFP3 respirators during activities where prolonged close physical contact is required.

Municipality-level measles, mumps, and rubella (MMR) vaccine coverage and deprivation in Brazil: A nationwide ecological study, 2006 to 2020.

To better understand the declining rates of routine childhood vaccination in Brazil, we investigated the association between measles, mumps, and rubella (MMR) first dose vaccine coverage and deprivation at the municipality level. Using routinely collected data from 5565 Brazilian municipalities from 2006 to 2020, we investigated the association between municipality-level MMR vaccine first dose coverage (i.e., as a continuous variable and as a percentage of municipalities attaining the 95% target coverage) in relation to quintiles of municipality-level deprivation, measured by the Brazilian Deprivation Index (Índice Brasileiro de Privação, IBP), and geographic regions. From 2006 to 2020, the mean municipality-level MMR vaccine coverage declined across all deprivation quintiles and regions of Brazil, by an average of 1.2% per year. The most deprived quintile of municipalities had higher coverage on average, but also the steepest declines in coverage (i.e., an annual decline of 1.64% versus 0.61% in the least deprived quintile) in the period of 2006-2020, and the largest drop in coverage at the beginning of the COVID-19 pandemic (2019-2020). Across all deprivation quintiles and regions (except for the Southeast region), less than 50% of municipalities in Brazil met the 95% MMR coverage target in 2020.The decrease in MMR first dose vaccine coverage in Brazil is widespread, but steeper declines have been observed in the most deprived municipalities. To promote vaccine equity and prevent future outbreaks, further research is urgently needed to understand the causal mechanisms underlying the observed associations between municipality-level MMR vaccine coverage and deprivation.

Socioeconomic risk markers of arthropod-borne virus (arbovirus) infections: a systematic literature review and meta-analysis.

INTRODUCTION: Arthropod-borne viruses (arboviruses) are of notable public health importance worldwide, owing to their potential to cause explosive outbreaks and induce debilitating and potentially life-threatening disease manifestations. This systematic review and meta-analysis aims to assess the relationship between markers of socioeconomic position (SEP) and infection due to arboviruses with mosquito vectors. METHODS: We conducted a systematic search on PubMed, Embase, and LILACS databases to identify studies published between 1980 and 2020 that measured the association of SEP markers with arbovirus infection. We included observational studies without geographic location or age restrictions. We excluded studies from grey literature, reviews and ecological studies. Study findings were extracted and summarised, and pooled estimates were obtained using random-effects meta-analyses. RESULTS: We identified 36 observational studies using data pertaining to 106 524 study participants in 23 geographic locations that empirically examined the relationship between socioeconomic factors and infections caused by seven arboviruses (dengue, chikungunya, Japanese encephalitis, Rift Valley fever, Sindbis, West Nile and Zika viruses). While results were varied, descriptive synthesis pointed to a higher risk of arbovirus infection associated with markers of lower SEP, including lower education, income poverty, low healthcare coverage, poor housing materials, interrupted water supply, marital status (married, divorced or widowed), non-white ethnicities and migration status. Pooled crude estimates indicated an increased risk of arboviral infection associated with lower education (risk ratio, RR 1.5 95% CI 1.3 to 1.9); I2=83.1%), interruption of water supply (RR 1.2; 95% CI 1.1 to 1.3; I2=0.0%) and having been married (RR 1.5 95% CI 1.1 to 2.1; I2=85.2%). CONCLUSION: Evidence from this systematic review suggests that lower SEP increases the risk of acquiring arboviral infection; however, there was large heterogeneity across studies. Further studies are required to delineate the relationship between specific individual, household and community-level SEP indicators and arbovirus infection risks to help inform targeted public health interventions. PROSPERO REGISTRATION NUMBER: CRD42019158572.

Investigation of a SARS-CoV-2 Outbreak at an Automotive Manufacturing Site in England.

Workplace-related outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to occur globally. The manufacturing sector presents a particular concern for outbreaks, and a better understanding of transmission risks are needed. Between 9 March and 24 April 2021, the COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook a comprehensive investigation of a SARS-CoV-2 outbreak at an automotive manufacturing site in England. The site had a total of 266 workers, and 51 SARS-CoV-2 infections. Overall, ventilation, humidity, and temperature at the site were assessed to be appropriate for the number of workers and the work being conducted. The company had implemented a number of infection control procedures, including provision of face coverings, spacing in the work, and welfare areas to allow for social distancing. However, observations of worker practices identified lapses in social distancing, although all were wearing face coverings. A total of 38 workers, including four confirmed cases, participated in the COVID-OUT study. The majority of participants received COVID-19 prevention training, though 42.9% also reported that their work required close physical contact with co-workers. Additionally, 73.7% and 34.2% had concerns regarding reductions in future income and future unemployment, respectively, due to self-isolation. This investigation adds to the growing body of evidence of SARS-CoV-2 outbreaks from the manufacturing sector. Despite a layered COVID-19 control strategy at this site, cases clustered in areas of high occupancy and close worker proximity.

Epidemic preparedness: Prenatal Zika virus screening during the next epidemic.

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of Congenital Zika Syndrome as a public health problem and the existence of analogous congenital prenatal screening programmes for STORCH agents (syphilis, toxoplasmosis, others (eg, human immunodeficiency virus, varicella-zoster virus, parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus). However, our assessment also reveals key barriers to implementation, such as the need for more accurate diagnostic tests, effective antiviral treatments, increased social service capacity, and surveillance. Given that the reemergence of ZIKV is likely, we provide a guiding framework for policymakers and public health leaders that can be further elaborated and adapted to different contexts in order to reduce the burden of adverse ZIKV-related birth outcomes during future outbreaks.

A primate model of severe malarial anaemia: a comparative pathogenesis study.

Severe malarial anaemia (SMA) is the most common life-threatening complication of Plasmodium falciparum infection in African children. SMA is characterised by haemolysis and inadequate erythropoiesis, and is associated with dysregulated inflammatory responses and reduced complement regulatory protein levels (including CD35). However, a deeper mechanistic understanding of the pathogenesis requires improved animal models. In this comparative study of two closely related macaque species, we interrogated potential causal factors for their differential and temporal relationships to onset of SMA. We found that rhesus macaques inoculated with blood-stage Plasmodium coatneyi developed SMA within 2 weeks, with no other severe outcomes, whereas infected cynomolgus macaques experienced only mild/ moderate anaemia. The abrupt drop in haematocrit in rhesus was accompanied by consumption of haptoglobin (haemolysis) and poor reticulocyte production. Rhesus developed a greater inflammatory response than cynomolgus macaques, and had lower baseline levels of CD35 on red blood cells (RBCs) leading to a significant reduction in the proportion of CD35+ RBCs during infection. Overall, severe anaemia in rhesus macaques infected with P. coatneyi has similar features to SMA in children. Our comparisons are consistent with an association of low baseline CD35 levels on RBCs and of early inflammatory responses with the pathogenesis of SMA.

Induction of immunity following vaccination with a chemically attenuated malaria vaccine correlates with persistent antigenic stimulation.

Objectives: Blood stage malaria parasites attenuated with seco-cyclopropyl pyrrolo indole (CPI) analogues induce robust immunity in mice to homologous and heterologous malaria parasites and are being considered for the development of a human vaccine. However, it is not understood how attenuated parasites induce immunity. We showed that following vaccination, parasite DNA persisted in blood for several months, raising the possibility that ongoing immune stimulation may be critical. However, parasites were not seen microscopically beyond 24 h postvaccination. We aimed to provide a mechanistic understanding of immune induction. Methods: Mice were vaccinated with chemically attenuated Plasmodium chabaudi parasites. PCR and adoptive transfer studies were used to determine the presence of parasites and antigen in vivo. In other experiments, Plasmodium falciparum parasitised red blood cells were attenuated in vitro and RNA and antigen expression studied. Results: We show that blood transferred from vaccinated mice into naïve mice activates T cells and induces complete protective immunity in the recipient mice strongly suggesting that there is persistence of parasite antigen postvaccination. This is supported by the presence of parasite RNA in vaccinated mice and both RNA and antigen expression in P. falciparum cultures treated with CPI drugs in vitro. In addition, drugs that block parasite growth also prevent the induction of immunity in vaccinated mice, indicating that some growth of attenuated parasites is required for immune induction. Conclusions: Attenuated parasites persist at submicroscopic levels in the blood of mice postvaccination with the ability to activate T cells and induce ongoing protective immune responses.