What to Do in the Next Pandemic Outbreak: Natural Herd Immunity Versus Lockdown (Lessons Learned from COVID-19).

The purpose of this article is to analyse non-pharmaceutical approaches to control pandemics. Currently vaccines are our best hope to control the COVID-19 pandemic, but before the appearance of the first vaccines the available possibilities were much more limited. While most people worldwide were confined to their homes to slow the spread of the new coronavirus, some countries (most notably the United Kingdom) advocated infecting the majority of the community, aiming to achieve what has been called "herd immunity". This article focuses on two non-therapeutic strategies for dealing with deadly viruses and points out their respective problems: natural herd immunity and quarantines/lockdowns. It analyses these strategies from three perspectives: legal, ethical and social. The article concludes that in the absence of therapeutic alternatives (vaccines), short-term lockdowns are necessary, but long-term lockdowns are legally, ethically, socially and financially impossible to sustain.

Understanding protection from SARS-CoV-2 using metabolomics.

The COVID-19 pandemic is still raging in most countries. Although the recent mass vaccination campaign has opened a new chapter in the battle against SARS-CoV-2, the world is still far from herd immunity. There is an urgent need to identify healthy people at high risk of contracting COVID-19, as well as supplements and nutraceuticals that can reduce the risk of infection or mitigate symptoms. In the present study, a metabolic phenotype that could protect individuals from SARS-CoV-2 infection or predispose them to developing COVID-19 was investigated. Untargeted metabolomics was performed on serum samples collected from 51 healthcare workers who were in good health at the beginning of the COVID-19 outbreak in Italy, and who were later exposed to the same risk of developing COVID-19. Half of them developed COVID-19 within three weeks of the blood collection. Our results demonstrate the presence of a specific signature associated with protection from SARS-CoV-2. Circulating monolaurin, which has well-known antiviral and antibacterial properties, was higher in protected subjects, suggesting a potential defensive role against SARS-CoV-2 infection; thus, dietary supplements could boost the immune system against this infection. In addition, our data demonstrate that people with higher levels of cholesterol are at higher risk of developing COVID-19. The present study demonstrates that metabolomics can be of great help for developing personalized medicine and for supporting public healthcare strategies. Studies with larger cohorts of subjects are necessary to confirm our findings.

Vaccines: Underlying Principles of Design and Testing.

In this paper, we review the key elements that should be considered to take a novel vaccine from the laboratory through to licensure in the modern era. This paper is divided into four sections. First, we discuss the host immune responses that we engage with vaccines. Second, we discuss how in vivo and in vitro studies can inform vaccine design. Third, we discuss different vaccine modalities that have been licensed or are in testing in humans. Last, we overview the basic principles of vaccine approvals. Throughout we provide real-world examples of vaccine development against infectious diseases, including coronavirus disease 2019 (COVID-19).

Impact of Microbiota: A Paradigm for Evolving Herd Immunity against Viral Diseases.

Herd immunity is the most critical and essential prophylactic intervention that delivers protection against infectious diseases at both the individual and community level. This process of natural vaccination is immensely pertinent to the current context of a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection around the globe. The conventional idea of herd immunity is based on efficient transmission of pathogens and developing natural immunity within a population. This is entirely encouraging while fighting against any disease in pandemic circumstances. A spatial community is occupied by people having variable resistance capacity against a pathogen. Protection efficacy against once very common diseases like smallpox, poliovirus or measles has been possible only because of either natural vaccination through contagious infections or expanded immunization programs among communities. This has led to achieving herd immunity in some cohorts. The microbiome plays an essential role in developing the body's immune cells for the emerging competent vaccination process, ensuring herd immunity. Frequency of interaction among microbiota, metabolic nutrients and individual immunity preserve the degree of vaccine effectiveness against several pathogens. Microbiome symbiosis regulates pathogen transmissibility and the success of vaccination among different age groups. Imbalance of nutrients perturbs microbiota and abrogates immunity. Thus, a particular population can become vulnerable to the infection. Intestinal dysbiosis leads to environmental enteropathy (EE). As a consequence, the generation of herd immunity can either be delayed or not start in a particular cohort. Moreover, disparities of the protective response of many vaccines in developing countries outside of developed countries are due to inconsistencies of healthy microbiota among the individuals. We suggested that pan-India poliovirus vaccination program, capable of inducing herd immunity among communities for the last 30 years, may also influence the inception of natural course of heterologous immunity against SARS-CoV-2 infection. Nonetheless, this anamnestic recall is somewhat counterintuitive, as antibody generation against original antigens of SARS-CoV-2 will be subdued due to original antigenic sin.

Consensus recommendations on calf- and herd-level passive immunity in dairy calves in the United States.

Passive immunity in calves is evaluated or quantified by measuring serum or plasma IgG or serum total protein within the first 7 d of age. While these measurements inform about circulating concentrations of this important protein, they are also a proxy for evaluating all of the additional benefits of colostral ingestion. The current individual calf standard for categorizing dairy calves with successful passive transfer or failure of passive transfer of immunity are based on serum IgG concentrations of ≥10 and <10 g/L, respectively. This cutoff was based on higher mortality rates in calves with serum IgG <10 g/L. Mortality rates have decreased since 1991, but the percentage of calves with morbidity events has not changed over the same time period. Almost 90% of calves sampled in the USDA National Animal Health Monitoring System's Dairy 2014 study had successful passive immunity based on the dichotomous standard. Based on these observations, a group of calf experts were assembled to evaluate current data and determine if changes to the passive immunity standards were necessary to reduce morbidity and possibly mortality. In addition to the USDA National Animal Health Monitoring System's Dairy 2014 study, other peer-reviewed publications and personal experience were used to identify and evaluate potential standards. Four options were evaluated based on the observed statistical differences between categories. The proposed standard includes 4 serum IgG categories: excellent, good, fair, and poor with serum IgG levels of ≥25.0, 18.0-24.9, 10.0-17.9, and <10 g/L, respectively. At the herd level, we propose an achievable standard of >40, 30, 20, and <10% of calves in the excellent, good, fair, and poor categories, respectively. Because serum IgG concentrations are not practical for on-farm implementation, we provide corresponding serum total protein and %Brix values for use on farm. With one-third of heifer calves in 2014 already meeting the goal of ≥25 g/L serum IgG at 24 h of life, this achievable standard will require more refinement of colostrum management programs on many dairy farms. Implementation of the proposed standard should further reduce the risk of both mortality and morbidity in preweaned dairy calves, improving overall calf health and welfare.

Technical note: Evaluation of digital refractometers to estimate serum immunoglobulin G concentration and passive transfer in Jersey calves.

Previous data have demonstrated that refractometers can be used to estimate serum IgG, and that a cut-point of 7.8% Brix should be used to identify failure of passive transfer (FPT) in 1-d-old Holstein calves. The objective of the present study was to validate the use of refractometry to estimate serum IgG concentrations and evaluate FPT in Jersey calves. Blood samples (n = 97) were obtained from 1- to 3-d-old Jersey calves and centrifuged at 3,300 × g for 20 min at 25°C. Serum was analyzed for % Brix, total protein (TP), and refractive index (nD) using a Sper Scientific Digital Refractometer (model #300036, Sper Scientific, Scottsdale, AZ) within 12 h of sampling. Samples were then frozen and later analyzed in the laboratory for IgG by radial immunodiffusion. The mean serum IgG concentration for all calves was 23.7 mg/mL (SD = 12.5), with a range of 2.3 to 65.5 mg/mL. Mean serum % Brix was 8.9 (SD = 1.1; range 6.5 to 12.0). Serum % Brix was moderately correlated with IgG concentration (r = 0.77). Total protein and IgG were moderately correlated (r = 0.790). Regression was used to determine cut-points for approximately 10, 12, and 14 mg of IgG/mL and to determine the sensitivity and specificity of refractometry to identify FPT (serum IgG <10 mg/mL at 24 h of life). Brix cut-points analyzed were 7.1, 7.3, and 7.6%; TP cut-points were 4.6, 5.0, and 5.5 g/dL; and nD cut-points were 1.34332, 1.34271, and 1.3448, respectively, for 10, 12, and 14 mg of IgG/mL. The 7.3% Brix and 4.6 g/dL TP cut-points resulted in the greatest percentage of samples being correctly classified. These data suggest that digital refractometry is an acceptable and rapid method to estimate immunoglobulin G in Jersey calf serum.

Hurdles to herd immunity: Distrust of government and vaccine refusal in the US, 2002-2003.

High rates of nonmedical exemptions (NMEs) from required childhood vaccinations have contributed to outbreaks of vaccine-preventable diseases, such as measles and pertussis. Understanding the parental decision to obtain an NME could help health professionals and public health programs improve vaccination rates in areas with high vaccine refusal. Using a 2002-2003 multi-state survey of parents of school age children (​n=2445), this study found that parental distrust of the government and of healthcare providers is a significant factor related to a number of vaccine-related beliefs and behaviors. The odds that parents who distrust the government have seen a complementary/alternative medicine (CAM) provider were 2.11 times greater than those of parents who trust the government (70.1% vs 52.6%; OR, 2.11; 95% CI, 1.59-2.84; P<0.01). Parents who distrust the government had increased odds of trusting vaccine information from CAM providers compared to trusting parents (57.9% vs 46.3%; OR, 1.53; 95% CI, 1.16-2.01; P<0.01). Parents who distrust the government also had increased odds of distrusting vaccine information acquired at their healthcare providers' offices (12.6% vs 4.7%; OR, 2.64; 95% CI, 1.64-4.24; P<0.01). Distrustful parents had increased odds of thinking government sources of information about vaccines were unreliable, categorizing the CDC, the Food and Drug Administration (FDA), or local and state health departments as poor or very poor sources (distrust government vs trust government: 25.2% vs 11.7%; OR, 2.39; 95% CI, 1.70-3.36; P<0.01; distrust healthcare providers vs trust healthcare providers: 24.4% vs 11.4%; OR, 2.44; 95% CI, 1.75-3.38; P<0.01). These findings indicate that distrustful parent populations may need to be reached through modalities outside of traditional government and healthcare provider communications. Research into new and more effective techniques for delivering pro-vaccine messages is warranted.

Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden.

The effects of pneumococcal conjugated vaccines (PCVs) need to be investigated. In Stockholm County, Sweden, PCV7 was introduced in the childhood immunisation programme in 2007 and changed to PCV13 in 2010.Over 90% of all invasive isolates during 2005-2014 (n=2336) and carriage isolates, 260 before and 647 after vaccine introduction, were characterised by serotyping, molecular typing and antibiotic susceptibility, and serotype diversity was calculated. Clinical information was collected for children and adults with invasive pneumococcal disease (IPD).The IPD incidence decreased post-PCV7, but not post-PCV13, in vaccinated children. Beneficial herd effects were seen in older children and adults, but not in the elderly. The herd protection was more pronounced post-PCV7 than post-PCV13. PCV7 serotypes decreased. IPD caused by PCV13 serotypes 3 and 19A increased post-PCV7. Post-PCV13, serotypes 6A and 19A, but not serotype 3, decreased. The serotype distribution changed in carriage and IPD to nonvaccine types, also in nonvaccinated populations. Expansion of non-PCV13 serotypes was largest following PCV13 introduction. Serotype diversity increased and nonvaccine clones emerged, such as CC433 (serotype 22F) in IPD and CC62 (serotype 11A) in carriage. In young children, meningitis, septicaemia and severe rhinosinusitis, but not bacteraemic pneumonia, decreased.Pneumococcal vaccination leads to expansion of new or minor serotypes/clones, also in nonvaccinated populations.

The cost-burden of paediatric pneumococcal disease in Sweden and the potential cost-effectiveness of prevention using 7-valent pneumococcal vaccine.

AIMS: A cost-effectiveness model was used to estimate the change in disease burden that might be expected if PCV7 was included as part of the routine 3-dose vaccination schedule in Sweden. METHODS: An economic model was populated with data from the main clinical PCV7 efficacy trials, demographic data from government sources, surveillance and epidemiologic data from the US and Nordic region, and average treatment costs, considering the impact of disease on the whole national population. RESULTS: The model estimated that PCV7 would prevent 18,856 cases of AOM, 684 of pneumonia, 86 of pneumococcal bacteraemia and 21 cases of pneumococcal meningitis in children <10 years, further 221 cases of IPD would be avoided in older children and adults and 397 cases of pneumonia in adults aged 18-39 years. Annually, 4 childhood (<10 years) deaths and 39 deaths in older children and adults would be prevented, resulting in an annual saving of 632 life years. The reduction of cost for the society was estimated to 27.9 (-205, +160) million SEK. The sensitivity analysis showed that it was most sensitive to the efficacy of the vaccine against AOM, the cost of managing infections and the incidence of all disease. CONCLUSION: This model demonstrates that implementing a universal vaccine programme in Sweden with PCV7 would be cost-effective with an estimated net reduction of costs for the society.

Vaccine preventable diseases and vaccination policy for indigenous populations.

Compared with nonindigenous people, indigenous people in first-world countries have experienced much higher rates of many vaccine preventable diseases. This systematic review of published scientific literature, government reports, and immunization guidelines from Australia, Canada, New Zealand, and the United States compares pre- and postvaccination disease rates and vaccination policy for indigenous people in these four countries. Nationally funded universal vaccination programs are clearly the most effective way of reducing disease in indigenous populations. Most successful have been programs for viral diseases in which strain variations are not important and herd immunity is high, such as measles and hepatitis B. For bacterial infections, strain variations (pneumococcal disease), heavy nasopharyngeal colonization of young infants (pneumococcal and Haemophilus influenzae type b disease), low vaccine effectiveness in adults with a high prevalence of risk factors (polysaccharide pneumococcal vaccine), and waning immunity (pertussis) have been associated with continuing or widening disparities between indigenous and nonindigenous populations. However, universal vaccination programs are not always possible. Geographic targeting of all persons in certain regions with high disease rates has been successful, as has targeting of indigenous populations in regions where they constitute larger proportions of the population. In national programs targeting only indigenous people, it has been difficult to achieve high coverage, particularly in urban areas. Innovative program approaches are particularly needed in these situations.

[Adult vaccination update]. / Actualización en la vacunación del adulto.

Vaccination, as a global concept, is the most cost-effective strategy in primary prevention of communicable diseases. One of the bigger difficulties in adult population is to reach the same vaccine coverage as in childhood vaccine programs. In order to solve this deficit, strategies established in the primary level are basic, due the fact that it's the first contact of adult population with health programs. Tertiary level could help to optimize vaccine coverage in specific groups. Active immunization in adults is established evaluating factors as age and gender, but specific circumstances associated with medical conditions, treatments or occupation could extend vaccine administration in adults.

Actualización en la vacunación del adulto / Adult vaccination update

La vacunación, en su concepto global, es la estrategia más coste-efectiva en la prevención primaria de enfermedades trasmisible. Una de las mayores dificultades en la población adulta es alcanzar coberturas vacunales semejantes a las de los programas infantiles. Para solucionar dicho déficit, las estrategias desde el nivel de contacto de lapoblación adulta con los programas de salud. Otros niveles, como elterciario, pueden optar a optimizar la cobertura vacunal en grupos específicos de riesgo. La inmunoterapia activa en el adulto se planifica sobre factores de edad y sexo, pero se añaden circunstancias especiales derivadas de situaciones clínicas, terapéuticas, ocupacionales y otras que pueden ampliar el espectro de inmunógenos a administrar a un adulto (AU)