Restoring Trust: The Need for Precision Medicine in Infectious Diseases, Public Health and Vaccines.

There are limited data on precision medicine in infectious diseases and vaccines; however, precise management of infectious diseases plays a critical role in trust for government, health-care organizations, science, and pharma. The improvement in biomedical technologies, availability of large clinical and -omic data and appropriate application of artificial intelligence may allow precision in vaccines and public health and restore trust. This is an invited editorial on the role of precision medicine in infectious diseases and vaccines.

COVID-19 risk perception, cognitive dissonance, and vaccine hesitancy.

The COVID-19 pandemic has shown that despite having high risk for severe disease, some individuals had low-risk perception and consequently they refused vaccination. This was more common among individuals with distrust in the government and the scientific organizations. Cognitive dissonance occurs when a person participates in an action that goes against one's beliefs. In order to reduce the dissonance, the individual often avoids the action. Recently, dissonance-based interventions have been shown to be effective in changing various health, environmental, and social behaviors. The impact of these interventions may persist for several years. Cognitive dissonance may be another mechanism for vaccine refusal among people with mistrust in the system. There is a need to investigate the role of cognitive dissonance in vaccine refusal and the effectiveness of dissonance-based interventions to reduce vaccine hesitancy among individuals with high risk for severe disease and low vaccination rates.

Corrigendum to: 2531. Using Peer-to-Peer Education to Increase Awareness and Uptake of HPV Vaccine Among Chinese International Students.

[This corrects the article DOI: 10.1093/ofid/ofz360.2209.].

Human papillomavirus and Chinese international students in the United States: attitudes, knowledge, vaccination trends, healthcare behaviors, and sexual activity.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world, with the ability to cause external genital warts and cancers. The HPV vaccine, first released in the United States of America (USA) in 2006, has been shown to protect against the highest risk HPV strains responsible for the majority of HPV-related cancers. In mainland China, the HPV vaccine was only recently approved in 2016 and is therefore not readily available. As a result, Chinese international students (CIS) studying in the USA continue to have low HPV vaccination rates. This study completed in person and online surveying of 396 CIS at a large Southern California university, with the goal of better understanding CIS knowledge and awareness of HPV disease, vaccination and healthcare behaviors, and sexual activity. Among participants, the reported HPV vaccination rate was 61% (females: 85%; males: 32%). HPV vaccination was significantly correlated with a past visit to the on-campus student health center, having university-sponsored student health insurance, higher self-perceived HPV knowledge, and increased willingness to pay for vaccination. A large portion of participants portrayed low levels of sexual activity, which suggests that CIS can take advantage of catch-up HPV vaccination recommendations through 26 years of age. The results of this study can be used to inform policy initiatives, particularly at the campus level, that attempt to improve HPV vaccination rates amongst CIS.

COVID-19 vaccine hesitancy: misinformation and perceptions of vaccine safety.

Despite COVID-19's devastating toll, many Americans remain unwilling to receive the COVID-19 vaccine. The authors conducted a US national survey to understand the health literacy of adults regarding the vaccine, as well as their COVID-19 beliefs and experiences. People who believed the COVID-19 vaccine was unsafe were less willing to receive the vaccine, knew less about the virus and were more likely to believe COVID-19 vaccine myths. On average, they were less educated, lower income, and more rural than people who believed the vaccine is safe. The results highlight the importance of developing clear health communications accessible to individuals from varied socioeconomic and educational backgrounds.

Intra-nasal zinc level relationship to COVID-19 anosmia and type 1 interferon response: A proposal.

Anosmia is common among COVID-19 patients and anosmia assessment is proposed to be useful in the early diagnosis and prognosis of patients. Data on the pathogenesis of anosmia during COVID-19 suggest potential olfactory nerve involvement. Zinc is an essential micronutrient that regulates the immune responses, and zinc deficiency is known to induce anosmia and ageusia. We previously proposed that a drop in nasal zinc level is a normal nasal immune response to acute viral infections, including SARS-CoV-2 infection, and play a role in the pathogenesis of anosmia. The drop in the local zinc level in response to SARS-CoV-2 may lead to lower type 1 interferons and shift toward Th2 immune responses; if prolonged, it may lead to increased viral replication and more severe disease. In people who are at risk for baseline systemic zinc deficiency, such as the elderly and those with chronic diseases such as, chronic lung disease, diabetes, cardiovascular disease, and cancer, SARS-CoV-2 infection-induced drop in nasal zinc level may be more severe and prolonged and lead to an insufficient anti-viral nasal immune response and control the spread of the virus systemically and to the lungs. A better understanding of the clinical implications of baseline systemic zinc deficiency on anosmia and nasal immune responses may allow the development of new treatment strategies to slow down or stop the systemic invasion of SARS-CoV-2.

The role of the thymus in COVID-19 disease severity: implications for antibody treatment and immunization.

The thymus is a largely neglected organ but plays a significant role in the regulation of adaptive immune responses. The effect of aging on the thymus and immune senescence is well established, and the resulting inflammaging is found to be implicated in the development of many chronic diseases including atherosclerosis, hypertension and type 2 diabetes. Both aging and diseases of inflammaging are associated with severe COVID-19 disease, and a dysfunctional thymus may be a predisposing factor. In addition, insults on the thymus during childhood may lead to abnormal thymic function and may explain severe COVID-19 disease among younger individuals; therefore, measurement of thymic function may assist COVID-19 care. Those with poor thymic function may be treated prophylactically with convalescent serum or recombinant antibodies, and they may respond better to high-dose or adjuvanted COVID-19 vaccines. Treatments inducing thymic regeneration may improve patients' overall health and may be incorporated in COVID-19 management.

Neutralizing and cross-reacting antibodies: implications for immunotherapy and SARS-CoV-2 vaccine development.

The novel coronavirus SARS-CoV-2 emerged in China in 2019 and quickly spread globally, causing a pandemic. There is an urgent need to develop vaccines against the virus, and both convalescent plasma and immune globulin are currently in clinical trials for treatment of patients with COVID-19. It is unclear whether antibodies induced by SARS-CoV-2 have neutralizing capacity and whether they can protect from future infection. Seasonal human coronaviruses (HCoV) have been circulating for decades. It is currently unknown whether antibodies against seasonal HCoV may cross-neutralize SARS-CoV-2. Data from neonates suggest that trans-placental antibodies against HCoV may have neutralizing capacity. Here we briefly review the epidemiologic observations on HCoV and discuss the potential implications for neutralizing and cross-neutralizing antibodies against SARS-CoV-2.

The role of the IL-1 system in pregnancy and the use of IL-1 system markers to identify women at risk for pregnancy complications†.

The interleukin (IL)-1 system plays a major role in immune responses and inflammation. The IL-1 system components include IL-1α, IL-1ß, IL-1 receptor type 1 and IL-1 receptor type 2 (decoy receptor), IL-1 receptor accessory protein, and IL-1 receptor antagonist (IL-1Ra). These components have been shown to play a role in pregnancy, specifically in embryo-maternal communication for implantation, placenta development, and protection against infections. As gestation advances, maternal tissues experience increasing fetal demand and physical stress and IL-1ß is induced. Dependent on the levels of IL-1Ra, which regulates IL-1ß activity, a pro-inflammatory response may or may not occur. If there is an inflammatory response, prostaglandins are synthesized that may lead to myometrial contractions and the initiation of labor. Many studies have examined the role of the IL-1 system in pregnancy by independently measuring plasma, cervical, and amniotic fluid IL-1ß or IL-1Ra levels. Other studies have tested for polymorphisms in IL-1ß and IL-1Ra genes in women experiencing pregnancy complications such as early pregnancy loss, in vitro fertilization failure, pre-eclampsia and preterm delivery. Data from those studies suggest a definite role for the IL-1 system in successful pregnancy outcomes. However, as anticipated, the results varied among different experimental models, ethnicities, and disease states. Here, we review the current literature and propose that measurement of IL-1Ra in relation to IL-1 may be useful in predicting the risk of poor pregnancy outcomes.

Assessing Front Office Staff Awareness on Mental Health Resources at Youth Friendly Clinics in Los Angeles County.

INTRODUCTION: Mental illness is a global health challenge and continues to rise among minors. Community clinics are well positioned to provide mental health services to young people. OBJECTIVE: To assess community clinic front staff awareness of recent legislation mandating access by minors to mental health services and the actual services delivered by these clinics. METHODS: We conducted a face-to-face survey with front office staff at community clinics in service planning areas (SPA) 6, 7, and 8 in Los Angeles County (LAC) to understand the staff awareness of the services provided to the minor by the clinic. These SPAs have been previously identified as serving a low socioeconomic population. Fisher's exact test and the chi-square test were conducted to understand the factors influencing the front desk personnel awareness. RESULTS: Data were collected from 17 clinics in SPA6, 15 clinics in SPA7, and 4 clinics in SPA8. All of the clinics provided Family-PACT insurance, resources for domestic abuse, intimate partner violence, mental health (such as anxiety and depression) and alcohol/drug abuse; however responding front desk staff in twenty-five out of 36 (69.4%) clinics was aware of the availability of Family-PACT insurance to minor patients; 21 (58.3%) was aware that the clinic provided resources for domestic abuse or intimate partner violence, and 20 (55.5%) was aware that the clinic offered resources for mental health (such as anxiety or depression) or alcohol/drug abuse to minor patients. DISCUSSION: In this pilot study, about half of the front desk staff at the surveyed clinics in LA County did not know that the clinic is fully authorized and equipped to provide mental health services to the minors (patients under 18 years of age). These are missed opportunities. There is a need for better education of the front-desk personnel.

A significant portion of college students are not aware of HPV disease and HPV vaccine recommendations.

There is limited data on the HPV immunization status of Latino/Hispanic youth in the USA. In Los Angeles County in 2015, 54,973 (34.3%) college students were of Latino/Hispanic background. We examined Los Angeles County college students' awareness of HPV and HPV-related disease, HPV vaccine recommendations, and their vaccination status. This study surveyed 212 Los Angeles college students from January to April 2018. In a convenience sampling study, a 31-question, IRB-approved survey was administered face-to-face to college students 18 years and older at California State University settings in Los Angeles County. Almost two-thirds of the male (65%) and half of the female (51.6%) respondents did not know that the HPV vaccine is recommended through 26 years of age, and 47.6% did not know they can get the HPV vaccine at the college student health center or youth-friendly clinics. Ethnicity, family income, and the highest level of education in the family had a significant impact on immunization rates. Self-reported and actual HPV knowledge levels were significantly associated with vaccination status. Educational strategies focusing on the logistics of receiving the HPV vaccine and HPV vaccine catch-up eligibility for college students may be effective in decreasing racial disparities in vaccine receipt.

Logistical and structural challenges are the major obstacles for family medicine physicians' ability to administer adult vaccines.

PURPOSE: This study was conducted to characterize the vaccination practices and challenges of family medicine physicians in Los Angeles County, California. METHODS: The Los Angeles Academy of Family Physicians (LA AFP) sent out electronic surveys to all of their active members (N = 1121) between December 2017 and January 2018, and asked them to answer questions about themselves, their practice, their patient population, and their immunization practices and challenges. We then analyzed the results through basic statistical calculations and Pearson's chi-squared tests. RESULTS: Seventy-four people (6.6%) responded to the survey, and 75% of responders stated that they administer all Advisory Committee on Immunization Practices (ACIP) recommended vaccines. The lowest vaccine administration rates were for the high-dose influenza vaccine, which 66.2% (n = 49) of respondents reported to administer, followed by the meningococcal B vaccine (68.9%; n = 51). The respondents who belonged to practices with more than 11 providers, were part of a large hospital or healthcare system, had electronic medical records (EMRs), and used the California Immunization Registry (CAIR) were more likely to report to vaccinate. The number one responding physician-reported challenge to vaccination was limited time and resources to address patient resistance followed by vaccine cost and lack of infrastructure to store vaccines. CONCLUSIONS: In this pilot study, structural and logistical challenges appeared to make the biggest impact on adult vaccination for the responding family medicine physicians. Solutions addressing these challenges will help improve the adult immunization rates.

Proposal to Reduce Adult Immunization Barriers in California.

Adult vaccination rates in the United States are consistently lower than the National Healthy People 2020 goals. Barriers to adult vaccination include inconsistency of insurance coverage of adult vaccines and difficulty in accessing vaccines. To help address the gap in adult access to vaccines, in 2016 the Department of Health Care Services--which administers the Medi-Cal program (California's version of Medicaid)--implemented the All Plan Letter (APL) 16-009, which requires coverage of recommended adult vaccines as a pharmacy benefit. Adult Medi-Cal patients can now receive the vaccines recommended for their age and underlying health conditions, and they can do so not only at a provider's office but also at local pharmacies, improving access and convenience. This policy brief recommends expanding coverage of all adult vaccines as a pharmacy benefit of all public and commercial insurance plans.

UV Protection by Natural Products: C. myrrha Oil Versus Sunscreen.

Exposure to various types of ultraviolet (UV) radiation from the sun has been linked to skin cancer. Use of sunscreen can reduce the damaging and carcinogenic effects of UV radiation. However, multiple chemicals in sunscreen can trigger allergic responses, making people less inclined to use sunscreen. Thus, finding natural, plant-based alternatives to sunscreen with similar efficacy has become an important area of research. Myrrh oil, extracted from the shrub Commiphora myrrha, has been used in the treatment of topical wounds and studies have shown that it may provide protection against solar radiation. This study sought to further investigate if C. myrrha oil can confer protection against UV radiation. A UV-sensitive strain of Saccharomyces cerevisiae was grown in petri dishes with one half covered by aluminum foil and the other half covered by clear polyethylene food wrap. The polyethylene half was treated with either SPF 15 or SPF 30 sunscreen, C. myrrha oil or a combination of C. myrrha oil and either sunscreen. The plates were exposed to sunlight. Colony death was quantified using visual estimation. While UV blocking by C. myrrha oil alone was not as effective as that by the synthetic sunscreen, the 1:1 combination of C. myrrha oil and SPF 15 sunblock was significantly more effective than SPF 15 sunblock alone to prevent S. cerevisiae death. These data suggest that naturally-based sunscreens supplemented with synthetic UV deterrents may provide a more holistic approach to prevent UV-induced skin damage. J Drugs Dermatol. 2018;17(8):905-907.

Foam soap is not as effective as liquid soap in eliminating hand microbial flora.

Foam soaps are aerosolized liquid soaps dispensed through a special pump mechanism. Currently there are no studies comparing liquid soap with foam soap in regard to efficacy of reducing hand microbial burden. In 3 separate experiments and with 2 different brands of foam soap, it was observed that nonantimicrobial foam soap was not as effective in reducing hand bacterial load as the liquid soap.

The effect of diabetes mellitus on outcomes of patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: data from a prospective double-blind clinical trial comparing treatment with linezolid versus vancomycin.

BACKGROUND: The presence of diabetes mellitus increases the risk of several severe infections, but data on its effect on treatment outcomes in patients with nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA) are limited. METHODS: We retrospectively analyzed data from a double-blind, randomized, multi-center, international clinical trial of culture-confirmed MRSA NP that compared treatment with linezolid to vancomycin. Specifically, we evaluated the clinical and microbiologic outcomes of patients with and without diabetes in the modified intent to treat population at end-of-treatment (EOT) and end-of-study (EOS, 7-30 days post-EOT). RESULTS: Among 448 enrolled patients 183 (40.8 %) had diabetes mellitus, 87 (47.5 %) of whom received linezolid and 96 (52.5 %) vancomycin. Baseline demographic and clinical characteristics were similar for the two treatment groups. Clinical success rates at EOS were 57.6 % with linezolid and 39.3 % with vancomycin, while microbiological success rates were 58.9 % with linezolid and 41.1 % with vancomycin. Among diabetic patients, rates of mortality and study drug-related adverse effects were similar between the treatment groups. Overall day 28 mortality rates were higher among diabetic patients compared to non-diabetic patients (23.5 vs 14.7 %, respectively: RD = 8.8 %, 95 % CI [1.4, 16.3]). CONCLUSIONS: Among diabetic patients with MRSA NP, treatment with linezolid, compared to vancomycin, was associated with higher clinical and microbiologic success rates, and comparable adverse event rates. TRIAL REGISTRATION: NCT00084266 .

Dietary vitamin D restriction in pregnant female mice is associated with maternal hypertension and altered placental and fetal development.

Epidemiology has linked vitamin D deficiency with preeclampsia in humans. We hypothesized that low vitamin D status in pregnant mice may lead to symptoms of preeclampsia. Female BL6 mice were raised on vitamin D-sufficient or -deficient diets from weeks 4 of age and then mated with vitamin D-sufficient BL6 males at week 8. The resulting pregnant mice were either allowed to deliver pups and monitored for blood pressure (BP) and weight of offspring or euthanized at day 14 or 18 of gestation (E14 or E18) for analysis of serum, placental/kidney tissues, and fetuses. At E14 serum concentrations of 25-hydroxyvitamin D (30.1 ± 5.0 vs 1.8 ± 0.6 ng/mL, P < .001) and 1,25-dihydroxyvitamin D (119.5 ± 18.7 vs 37.4 ± 5.1 pg/mL, P < .01) were higher in sufficient vs deficient pregnant mice. At E14 BP was significantly elevated in vitamin D-deficient pregnant mice relative to vitamin D-sufficient mice for both systolic BP (124.89 ± 2.28 vs 105.34 ± 3.61 mm Hg, P < .001) and mean arterial pressure (115.33 ± 1.93 vs 89.33 ± 5.02 mm Hg, P < .001). This elevation continued through pregnancy until 7 days postpartum (PP7) but returned to baseline by PP14. Analysis of maternal kidneys showed increased expression of mRNA for renin and the angiotensin II receptor (3- and 4-fold, respectively) in vitamin D-deficient vs -sufficient mice at E14. Histological analysis of E14 placentas from vitamin D-deficient mice showed decreased vascular diameter within the labyrinth region. E14 and E18 fetuses from vitamin D-deficient mice were larger than those from vitamin D-sufficient mothers. However, by PP14 pups from vitamin D-deficient mothers weighed significantly less than those from vitamin D-sufficient mothers. Resupplementation of vitamin D periconceptually partially reversed the effects of vitamin D deficiency. These data provide further evidence that low vitamin D status may predispose pregnant women to dysregulated placental development and elevated blood pressure.

Linezolid effects on bacterial toxin production and host immune response: review of the evidence.

BACKGROUND: Linezolid is active against a broad range of gram-positive pathogens and has the potential to also affect production of bacterial toxins and host immune function. OBJECTIVE: To assess the evidence for direct effects of linezolid on bacterial toxin synthesis and modulation of host immune responses. METHODS: Literature searches were performed of the PubMed and OVID databases. Reviews and non-English language articles were excluded. Articles with information on the effect of linezolid on bacterial toxin synthesis and immune responses were selected for further review, and data were summarized. RESULTS: Substantial in vitro evidence supports effects of linezolid on bacterial toxin production; however, the strength of the evidence and the nature of the effects are mixed. In the case of Staphylococcus aureus, repeated observations support the inhibition of production of certain staphylococcal toxins (Panton-Valentine leukocidin, protein A, and α- and ß-hemolysin) by linezolid, whereas only solitary reports indicate inhibition (toxic shock syndrome toxin-1, coagulase, autolysins, and enterotoxins A and B) or stimulation (phenol-soluble modulins) of toxin production by linezolid. In the case of Streptococcus pyogenes, there are solitary reports of linezolid inhibition (protein M, deoxyribonuclease, and streptococcal pyrogenic exotoxins A, B, and F) or stimulation (immunogenic secreted protein 2 and streptococcal inhibitor of complement-mediated lysis) of toxin production, whereas published evidence for effects on streptolysin O production is conflicting. In vitro data are limited, but suggest that linezolid might also have indirect effects on host cytokine expression through inhibition of bacterial production of toxins. In vivo data from preclinical animal studies and a single clinical study in humans are limited and equivocal insofar as a potential role for linezolid in modulating the host inflammatory response; this is due in part to the difficulty in isolating antimicrobial effects and toxin synthesis inhibitory effects of linezolid from any secondary effects on host inflammatory response. CONCLUSIONS: Available evidence supports the possibility that linezolid can inhibit, and in some cases stimulate, toxin production in clinically relevant pathogens. However, more research will be needed to determine the potential clinical relevance of those findings for linezolid.

Vitamin D and the regulation of placental inflammation.

The vitamin D-activating enzyme 1α-hydroxylase (CYP27B1) and vitamin D receptor (VDR) support anti-inflammatory responses to vitamin D in many tissues. Given the high basal expression of CYP27B1 and VDR in trophoblastic cells from the placenta, we hypothesized that anti-inflammatory effects of vitamin D may be particularly important in this organ. Pregnant wild type (WT) mice i.p. injected with LPS showed elevated expression of mouse Cyp27b1 (4-fold) and VDR (6-fold). Similar results were also obtained after ex vivo treatment of WT placentas with LPS. To assess the functional impact of this, we carried out ex vivo studies using placentas -/- for fetal (trophoblastic) Cyp27b1 or VDR. Vehicle-treated -/- placentas showed increased expression of IFN-γ and decreased expression of IL-10 relative to +/+ placentas. LPS-treated -/- placentas showed increased expression of TLR2, IFN-γ, and IL-6. Array analyses identified other inflammatory factors that are dysregulated in Cyp27b1(-/-) versus Cyp27b1(+/+) placentas after LPS challenge. Data highlighted enhanced expression of IL-4, IL-15, and IL-18, as well as several chemokines and their receptors, in Cyp27b1(-/-) placentas. Similar results for IL-6 expression were observed with placentas -/- for trophoblastic VDR. Finally, ex vivo treatment of WT placentas with the substrate for Cyp27b1, 25-hydroxyvitamin D(3), suppressed LPS-induced expression of IL-6 and the chemokine Ccl11. These data indicate that fetal (trophoblastic) vitamin D plays a pivotal role in controlling placental inflammation. In humans, this may be a key factor in placental responses to infection and associated adverse outcomes of pregnancy.