Vaccine Administration: The Growing Role of Prefilled Syringes

(Note: The MIDAS database reflects vaccine doses that are dispensed with a prescription in retail or hospital settings, so the COVID-19 vaccines and other public-health-administered vaccines are not fully reflected in that data set.) Stamoran adds, "However, across the rest of the world, vial-based vaccines still make up the majority of the volume dispensed." [...]there is plenty of room for growth for this newer administration device. [...]PFS are now widely used for annual flu shots, heparin injections, and a growing list of injectable therapies across multiple disease states. According to a 2021 article authored byGuillaume Lehee, R&D Innovation Leader for BD Medical-Pharmaceutical Systems, the use of PFS to vaccinate 300 million individuals in the United States in the event of a future pandemic could save more than three million hours of healthcare practitioners' time (1). [...]today's PFS are not yet proven to be compatible with ultrafrozen temperatures as the existing glass materials and other components may not stand up to the extremely low required temperatures," explains Stamoran.

Macerated stillbirth

Stillbirth is defined as the birth of a viable baby without signs of life. They account for more than 2.5 million intrauterine deaths per year worldwide and are associated with a number of risk factors, the most important of which are maternal and placental factors. Autopsy provides information that may be of use in determining time since death, gestational age of the fetus, mode of death, cause of fetal demise, and the likelihood of recurrence. The format of the autopsy is guided by parental consent, but even when consent is limited, valuable information may be obtained by careful consideration of antemortem test results, imaging, and genetic testing. Where there is a delay between death and delivery, fetuses are affected by maceration, which may increase the technical complexity of the autopsy and impart a number of artefactual changes, which should not be misinterpreted as genuine pathology. The most common pathologies encountered at autopsy are placental abnormalities, changes related to maternal disorders, malformations, and central nervous system pathology. © Springer Nature Switzerland AG 2022. All rights reserved.

A Dual-Approach Strategy to Optimize the Safety and Efficacy of Anti-Zika Virus Monoclonal Antibody Therapeutics.

Antibody-dependent enhancement of infection (ADE) is clinically relevant to Dengue virus (DENV) infection and poses a major risk to the application of monoclonal antibody (mAb)-based therapeutics against related flaviviruses such as the Zika virus (ZIKV). Here, we tested a two-tier approach for selecting non-cross-reactive mAbs combined with modulating Fc glycosylation as a strategy to doubly secure the elimination of ADE while preserving Fc effector functions. To this end, we selected a ZIKV-specific mAb (ZV54) and generated three ZV54 variants using Chinese hamster ovary cells and wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants as production hosts (ZV54CHO, ZV54WT, and ZV54ΔXF). The three ZV54 variants shared an identical polypeptide backbone, but each exhibited a distinct Fc N-glycosylation profile. All three ZV54 variants showed similar neutralization potency against ZIKV but no ADE activity for DENV infection, validating the importance of selecting the virus/serotype-specific mAbs for avoiding ADE by related flaviviruses. For ZIKV infection, however, ZV54CHO and ZV54ΔXF showed significant ADE activity while ZV54WT completely forwent ADE, suggesting that Fc glycan modulation may yield mAb glycoforms that abrogate ADE even for homologous viruses. In contrast to the current strategies for Fc mutations that abrogate all effector functions along with ADE, our approach allowed the preservation of effector functions as all ZV54 glycovariants retained antibody-dependent cellular cytotoxicity (ADCC) against the ZIKV-infected cells. Furthermore, the ADE-free ZV54WT demonstrated in vivo efficacy in a ZIKV-infection mouse model. Collectively, our study provides further support for the hypothesis that antibody-viral surface antigen and Fc-mediated host cell interactions are both prerequisites for ADE, and that a dual-approach strategy, as shown herein, contributes to the development of highly safe and efficacious anti-ZIKV mAb therapeutics. Our findings may be impactful to other ADE-prone viruses, including SARS-CoV-2.

A comprehensive insight on the challenges for COVID-19 vaccine: A lesson learnt from other viral vaccines.

The aim of this study is to comprehensively analyze previous viral vaccine programs and identify potential challenges and effective measures for the COVID-19 vaccine program. Previous viral vaccine programs, such as those for HIV, Zika, Influenza, Ebola, Dengue, SARS, and MERS, were evaluated. Paramount challenges were identified, including quasi-species, cross-reactivity, duration of immunity, revaccination, mutation, immunosenescence, and adverse events related to viral vaccines. Although a large population has been vaccinated, mutations in SARS-CoV-2 and adverse events related to vaccines pose significant challenges. Previous vaccine programs have taught us that predicting the final outcome of the current vaccine program for COVID-19 cannot be determined at a given state. Long-term follow-up studies are essential. Validated preclinical studies, long-term follow-up studies, alternative therapeutic approaches, and alternative vaccines are necessary.

Investigating the antiviral therapeutic potentialities of marine polycyclic lamellarin pyrrole alkaloids as promising inhibitors for SARS-CoV-2 and Zika main proteases (Mpro).

The new coronavirus variant (SARS-CoV-2) and Zika virus are two world-wide health pandemics. Along history, natural products-based drugs have always crucially recognized as a main source of valuable medications. Considering the SARS-CoV-2 and Zika main proteases (Mpro) as the re-production key element of the viral cycle and its main target, herein we report an intensive computer-aided virtual screening for a focused list of 39 marine lamellarins pyrrole alkaloids, against SARS-CoV-2 and Zika main proteases (Mpro) using a set of combined modern computational methodologies including molecular docking (MDock), molecule dynamic simulations (MDS) and structure-activity relationships (SARs) as well. Indeed, the molecular docking studies had revealed four promising marine alkaloids including [lamellarin H (14)/K (17)] and [lamellarin S (26)/Z (39)], according to their notable ligand-protein energy scores and relevant binding affinities with the SARS-CoV-2 and Zika (Mpro) pocket residues, respectively. Consequentially, these four chemical hits were further examined thermodynamically though investigating their MD simulations at 100 ns, where they showed prominent stability within the accommodated (Mpro) pockets. Moreover, in-deep SARs studies suggested the crucial roles of the rigid fused polycyclic ring system, particularly aromatic A- and F- rings, position of the phenolic -OH and δ-lactone functionalities as essential structural and pharmacophoric features. Finally, these four promising lamellarins alkaloids were investigated for their in-silico ADME using the SWISS ADME platform, where they displayed appropriated drug-likeness properties. Such motivating outcomes are greatly recommending further in vitro/vivo examinations regarding those lamellarins pyrrole alkaloids (LPAs).Communicated by Ramaswamy H. Sarma.

Vaccine development for mosquito-borne viral diseases.

Mosquito-borne viral diseases are a group of viral illnesses that are predominantly transmitted by mosquitoes, including viruses from the Togaviridae and Flaviviridae families. In recent years, outbreaks caused by Dengue and Zika viruses from the Flaviviridae family, and Chikungunya virus from the Togaviridae family, have raised significant concerns for public health. However, there are currently no safe and effective vaccines available for these viruses, except for CYD-TDV, which has been licensed for Dengue virus. Efforts to control the transmission of COVID-19, such as home quarantine and travel restrictions, have somewhat limited the spread of mosquito-borne viral diseases. Several vaccine platforms, including inactivated vaccines, viral-vector vaccines, live attenuated vaccines, protein vaccines, and nucleic acid vaccines, are being developed to combat these viruses. This review analyzes the various vaccine platforms against Dengue, Zika, and Chikungunya viruses and provides valuable insights for responding to potential outbreaks.

Reddit and Google Activity Related to Non-COVID Epidemic Diseases Surged at Start of COVID-19 Pandemic: Retrospective Study.

BACKGROUND: Resources such as Google Trends and Reddit provide opportunities to gauge real-time popular interest in public health issues. Despite the potential for these publicly available and free resources to help optimize public health campaigns, use for this purpose has been limited. OBJECTIVE: The purpose of this study is to determine whether early public awareness of COVID-19 correlated with elevated public interest in other infectious diseases of public health importance. METHODS: Google Trends search data and Reddit comment data were analyzed from 2018 through 2020 for the frequency of keywords "chikungunya," "Ebola," "H1N1," "MERS," "SARS," and "Zika," 6 highly publicized epidemic diseases in recent decades. After collecting Google Trends relative popularity scores for each of these 6 terms, unpaired 2-tailed t tests were used to compare the 2020 weekly scores for each term to their average level over the 3-year study period. The number of Reddit comments per month with each of these 6 terms was collected and then adjusted for the total estimated Reddit monthly comment volume to derive a measure of relative use, analogous to the Google Trends popularity score. The relative monthly incidence of comments with each search term was then compared to the corresponding search term's pre-COVID monthly comment data, again using unpaired 2-tailed t tests. P value cutoffs for statistical significance were determined a priori with a Bonferroni correction. RESULTS: Google Trends and Reddit data both demonstrate large and statistically significant increases in the usage of each evaluated disease term through at least the initial months of the pandemic. Google searches and Reddit comments that included any of the evaluated infectious disease search terms rose significantly in the first months of 2020 above their baseline usage, peaking in March 2020. Google searches for "SARS" and "MERS" remained elevated for the entirety of the 2020 calendar year, as did Reddit comments with the words "Ebola," "H1N1," "MERS," and "SARS" (P<.001, for each weekly or monthly comparison, respectively). CONCLUSIONS: Google Trends and Reddit can readily be used to evaluate real-time general interest levels in public health-related topics, providing a tool to better time and direct public health initiatives that require a receptive target audience. The start of the COVID-19 pandemic correlated with increased public interest in other epidemic infectious diseases. We have demonstrated that for 6 distinct infectious causes of epidemics over the last 2 decades, public interest rose substantially and rapidly with the outbreak of COVID-19. Our data suggests that for at least several months after the initial outbreak, the public may have been particularly receptive to dialogue on these topics. Public health officials should consider using Google Trends and social media data to identify patterns of engagement with public health topics in real time and to optimize the timing of public health campaigns.

Emerging Pandemic Infectious Disease Threats

Pandemic infectious diseases are caused by pathogens that have adapted well to growth and reproduction within the human host and that through unique environmental, socioeconomic, and cultural circumstances are able to rapidly spread across national boundaries and even globally. Although uncommon and caused by relatively few pathogens, the extraordinary human, economic, and societal losses caused by pandemic diseases as exemplified by coronavirus disease 2019 (COVID-19) make pandemic diseases of unique importance to clinicians, immunologists, and many other scientists and healthcare professionals. The pathogenesis of pandemic diseases is complex and unique to each pathogen, but common to all is widespread immunologic naïveté within the host population. In this chapter, we consider the pathogens of greatest concern for their pandemic potential. Most of these organisms are viruses, including betacoronaviruses, alpha influenza virus, Ebola virus, and the flaviviruses, but numerous bacteria are also emerging with pandemic disease potential. For each organism, we consider the factors, especially immunologic, that lead to pandemic spread and prospects for effective therapy and prevention. © 2023 Elsevier Ltd. All rights reserved.

Systemic Viral Infections and the Eye

Ocular manifestations of systemic viral infections are common. Because viral infection syndromes may be nonspecific, diagnosis of a particular viral infection often requires understanding of the risk factors and transmission modes of viral pathogens. Careful review of both history of the disease and the ocular exam findings can be helpful in narrowing down the differential diagnosis for the systemic condition and vice versa. A history of exposures, including animal exposures, sexual exposures, and travel, as well as the vaccination history and general medical history helps guide the workup and treatment of viral infections. Diagnostic testing for viral infections may include blood testing for serologic studies and viral detection, samples from involved extraocular organs, as well as ocular samples that can confirm a diagnosis and facilitate initiation of optimal therapy while minimizing side effects from exposure to unnecessary antiviral agents. Importantly, patients with HIV or other immunocompromising conditions may simultaneously have more than one active infection and also may manifest with syndromes that are atypical and have serologic testing that is less accurate. Careful and aggressive diagnostic evaluation of ocular symptoms is especially important in these patients, as are efforts to improve immune function while monitoring for the possible impact of immune reconstitution on the clinical course. © Springer Nature Switzerland AG 2022.

Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement.

To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.

Identifying and Managing Vector-Borne Diseases in Migrants and Recent Travelers in the Emergency Department.

Purpose of Review: Recognition and treatment of neglected tropical and vector-borne diseases is paramount as travel and immigration resume after a brief lull during the COVID-19 pandemic. These patients often present initially to the emergency department, and increasing physician knowledge of symptoms and treatment can reduce morbidity and mortality. This paper aims to summarize typical presentations of common tropical diseases, both neglected and vector borne, and provide the emergency physician with a diagnostic pathway based on current recommendations. Recent Findings: Co-circulation of ZIKV, CHIKV, and DENV is increasingly common in many countries throughout Caribbean and the Americas, requiring that patients be tested for each virus upon presentation. Dengvaxia is now approved as a vaccine against dengue in pediatric and young adult patients. A malaria vaccine, RTS,S/AS01, is currently in phase 3 trials and has been approved as a short-term vaccine by WHO for children in regions with high transmission risk after showing a 30% reduction in severe malaria. Mayaro is currently a neglected arbovirus that presents similarly to Chikungunya and is continuing to spread throughout the Americas at a rapid rate, gaining more attention after the 2016 Zika outbreak. Summary: Emergency physicians should consider internationally acquired illnesses to appropriately identify which patients require admission among well-appearing febrile immigrants or recent travelers presenting to the emergency department. Identifying symptomatology and understanding the appropriate workup and treatment for tropically acquired diseases will assist in recognizing severe complications with prompt treatment.

Outbreaks of different viral etiologies amidst COVID-19 pandemic

The COVID-19 pandemic has severely affected public health system and surveillance of other communicable diseases across the globe. The lockdown, travel constraints and COVID phobia turned down the number of people with illness visiting to the clinics or hospitals. Besides this, the heavy workload of SARS-CoV-2 diagnosis has led to the reduction in differential diagnosis of other diseases. Consequently, it added to the underlying burden of many diseases which remained under-diagnosed. Amidst the pandemic, the rise of emerging and re-emerging infectious diseases was observed worldwide and reported to the World Health Organization i.e., Crimean Congo Hemorrhagic Fever (2022, Iraq;2021 India), Nipah virus (2021, India), Zika virus (2021, India), and H5N1 influenza (2021, India), Monkeypox (2022, multicountry outbreak), Ebola virus disease (2022, DRC, Uganda;2021, DRC, Guinea;2020, DRC), Marburg (2022, Ghana;2021, Guinea), Yellow fever (2022, Uganda, Kenya, West and Central Africa;2021, Ghana, Venezuela, Nigeria;2020, Senegal, Guinea, Nigeria, Gabon;2020, Ethiopia, Sudan, Uganda), Dengue (2022, Nepal, Pakistan, Sao Tome, Temor-Leste;2021, Pakistan), Middle east respiratory syndrome coronavirus (2022, Oman, Qatar;2021, Saudi Arabia, UAE;2020, Saudi Arabia, UAE), Rift valley fever (2021, Kenya;2020, Mauritania), wild poliovirus type 1 (2022, Mozambique), Lassa fever (2022, Guinea, Togo, Nigeria;2020, Nigeria), Avian Influenza (H3N8) (2022, China), Avian Influenza (H5N1) (2022, USA), H10N3 influenza (2021, China), Hepatitis E virus (2022, Sudan), Measles (2022, Malawi, Afghanistan;2020, Burundi, Mexico), Mayaro virus disease (2020, French Guiana), Oropouche virus disease (2020, French Guiana). All these diseases were associated with high morbidity and burdened the public health system during the COVID-19 pandemic. During this critical public health menace, majority of the laboratory workforce was mobilized to the SARS-CoV-2 diagnosis. This has limited the surveillance efforts that likely led to under diagnosis and under-detection of many infectious pathogens. Lockdowns and travel limitations also put a hold on human and animal surveillance studies to assess the prevalence of these zoonotic viruses. In addition, lack of supplies and laboratory personnel and an overburdened workforce negatively impacted differential diagnosis of the diseases. This is especially critical given the common symptoms between COVID-19 and other pathogens causing respiratory illnesses. Additionally, the vaccination programs against various vaccine preventable diseases were also hampered which might have added to the disease burden. Despite these challenges, the world is better prepared to detect and respond to emerging/re-emerging pathogens. India now has more than 3000 COVID-19 diagnostic laboratories and an enhanced hospital infrastructure. In addition, mobile BSL-3 facilities are being validated for onsite sampling and testing in remote areas during outbreak situations and surveillance activities. This will undoubtedly be valuable as the COVID-19 pandemic evolves as well as during future outbreaks and epidemics. In conclusion, an increase in the emergence and re-emergence of viruses demonstrates that other infectious diseases have been neglected during the COVID-19 pandemic. Lessons learned from the infrastructure strengthening, collaborations with multiple stakeholders, increased laboratory and manufacturing capacity, large-scale COVID-19 surveillance, extensive network for laboratory diagnosis, and intervention strategies can be implemented to provide quick, concerted responses against the future threats associated with other zoonotic pathogens.

Inhibition of the SARS-CoV-2 Main Protease by Isoquercitrin γ-Cyclodextrin Inclusion Complex Formulations: A Biochemical and In Silico Study

The main protease (Mpro) of SARS-CoV-2 is a well-established drug target for rational drug design of COVID-19 inhibitors. To address the serious challenge of COVID-19, we have performed biochemical inhibition screens with recombinantly expressed SARS-CoV-2 main protease (Mpro). A fluorescent assay was used to identify the flavonoid isoquercitrin as an Mpro inhibitor. Both isoquercitrin encapsulated in γ-cyclodextrin (inclusion complex formulations) and alone inhibited SARS-CoV-2 Mpro. For isoquercitrin, a Ki value of 32 μM (IC50 = 63 μM) was obtained. Isoquercitrin γ-cyclodextrin inclusion complex formulations additionally inhibited Zika virus NS2B-NS3pro leading to an IC50 value of 98 μM. Formulations containing the other flavonoid compounds diosmetin-7-O-glucoside, hesperetin-7-O-glucoside, and naringenin-7-O-glucoside did not inhibit SARS-CoV-2 Mpro. Steady-state kinetics indicate that the inhibition mechanism of Mpro by isoquercitrin is potentially competitive. Molecular modeling studies carried out with MM/PBSA confirm the likely modes of isoquercitrin binding to both proteases. These modeling results can be used in the development of structural analogs of isoquercitrin with better inhibitory profiles and potential candidates for anti-coronavirus drugs. Since the targeted proteases are essential for viral activity, the delivery isoquercitrin-cyclodextrin inclusion complex formulations could be of great interest for the development of future antiviral drugs to target intracellular virus proteins or other components.

Plitidepsin Is a Broad-Spectrum Antiviral Shaping the Cell Proteostatic Balance

Background: Different viruses employ similar pathways for replication, revealing key intracellular hotspots to target with host-directed therapies and achieve a broad-spectrum antiviral activity. Plitidepsin is a clinically approved antitumoral agent that blocks the elongation factor eEF1A required for protein translation. This drug counteracts SARS-CoV-2 replication and shows a favorable safety profile in COVID-19 patients. Yet, the precise antiviral mechanism of action of plitidepsin remains unknown. Method(s): Here we used a deep quantitative proteomic analysis to measure the impact of plitidepsin on the proteome of SARS-CoV-2-infected Vero E6 cells. This was complemented with transmission electron microscopy assays, which unraveled the subcellular and morphological changes associated to plitidepsin treatment. In addition, we performed functional in vitro assays to dissect the antiviral activity of plitidepsin against SARS-CoV-2 and other viruses. Result(s): We found that this drug inhibited the synthesis of all SARS-CoV-2 proteins in a dose-dependent manner. These included the R1AB polyproteins, which facilitate the synthesis of non-structural proteins involved in the formation of double membrane vesicles (DMV) required for viral replication. Plitidepsin reduced DMV formation and the morphogenesis of new viruses, having a greater impact on viral than on host proteins. Less than 14% of the cellular proteome was significantly affected by plitidepsin, inducing the up-regulation of key molecules associated with protein biosynthesis, such as the translation initiation factors eIF4A2 and eIF2S3. Therefore, plitidepsin induced a compensatory state that rescued protein translation. This proteostatic response explains how cells preserve the cellular proteome after treatment with a translation inhibitor such as plitidepsin. In addition, it suggests that plitidepsin could inhibit other RNA-dependent and non-integrated DNA viruses, as we confirmed in vitro using Zika virus, Hepatitis C virus replicon and Herpes simplex virus. However, the compensatory proteostasis induced by plitidespin also explains why this drug failed to inhibit the replication of integrated DNA proviruses such as HIV-1. Conclusion(s): Unraveling the mechanism of action of host-directed therapies like plitidepsin is imperative to define the indications and antiviral profile of these compounds. This knowledge will be key to develop broad-spectrum treatments and have them ready to deploy when future pandemic viruses break through.

IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

Guillian-Barre Syndrome Post Covid-19 Vaccination

Case Report: This is a 50-year-old man that presented to the ED complaining of generalized weakness and acute loss of ability to ambulate which has been progressing for a month. Patient began having left arm and leg weakness, which started in his fingertips of his left upper extremity and soon moved proximally to upper left arm. Symptoms then progressed to right upper and lower arms. Symptoms further continued to progress making the patient bedridden. On presentation, CT head showed a C1/C2 subluxation possibly chronic without significant focal soft tissue swelling. CT cervical spine showed C1-C2 subluxation, possibly chronic. MRI of brain was unremarkable pre and postcontrast without focal findings or abnormal enhancement and showed redemonstration of the C1-C2 subluxation as described on CT scan. MRI of cervical spine showed at the level of C1 there is spinal canal stenosis. However, there is no direct pressure upon the cord/medulla. Upon evaluation, patient had significant motor weakness and required maximal assistance for movement. Patient was moreover noted to have flaccidity of muscles associated with weakness with no bulbar weakness. Patient had no difficulty in breathing or with speech. A lumbar tap was performed which showed elevated protein, WBC, and glucose. Upon further investigation, patient stated that he received his (3rd dose) of the Moderna Vaccine for Covid-19 about a month before the onset of symptoms and felt fine. Two weeks later, he began experiencing subjective fevers, diarrhea, abdominal pain, and fatigue that lasted for a week and then self-resolved. Approximately another two weeks later is when patient began noticing his neurological symptoms. Possible Guillain-Barre Syndrome post Campylobacter Jejuni (C. Jejuni) infection vs. post Covid-19 vaccine induced GBS was suspected at this point and patient was started on Intravenous Immunoglobulin (IVIG). Stool cultures were collected for C.Jejuni which came back negative. Gastrointestinal Pathogen Panel PCR Feces also came back negative. Patient was discharged to a rehab center and planned to receive another round of IVIG for 5 days. Conclusion(s): Guillain Barre Syndrome (GBS) is a rare immune-mediated neurological disorder affecting peripheral nerves and nerve roots, that presents as acute sensorimotor neuropathy starting with distal paresthesia that progresses to weakness of legs and arms, noteably, flaccid paralysis. GBS has several triggers namely infections such as C. jejuni, cytomegalovirus, M. pneumoniae, Epstien-Barr virus and Zika virus. There has also been several case reports and studies that have shown increased incidence of GBS vaccines such as influenza vaccine. Furthermore, there has been several studies that have linked GBS to COVID-19 vaccine. With COVID-19 cases continuing to persist, and increasing advocacy for vaccination against the disease, GBS should be considered as very rare but possible side effect of the vaccine.

A Perspective on Current Flavivirus Vaccine Development: A Brief Review.

The flavivirus genus contains several clinically important pathogens that account for tremendous global suffering. Primarily transmitted by mosquitos or ticks, these viruses can cause severe and potentially fatal diseases ranging from hemorrhagic fevers to encephalitis. The extensive global burden is predominantly caused by six flaviviruses: dengue, Zika, West Nile, yellow fever, Japanese encephalitis and tick-borne encephalitis. Several vaccines have been developed, and many more are currently being tested in clinical trials. However, flavivirus vaccine development is still confronted with many shortcomings and challenges. With the use of the existing literature, we have studied these hurdles as well as the signs of progress made in flavivirus vaccinology in the context of future development strategies. Moreover, all current licensed and phase-trial flavivirus vaccines have been gathered and discussed based on their vaccine type. Furthermore, potentially relevant vaccine types without any candidates in clinical testing are explored in this review as well. Over the past decades, several modern vaccine types have expanded the field of vaccinology, potentially providing alternative solutions for flavivirus vaccines. These vaccine types offer different development strategies as opposed to traditional vaccines. The included vaccine types were live-attenuated, inactivated, subunit, VLPs, viral vector-based, epitope-based, DNA and mRNA vaccines. Each vaccine type offers different advantages, some more suitable for flaviviruses than others. Additional studies are needed to overcome the barriers currently faced by flavivirus vaccine development, but many potential solutions are currently being explored.

2021 U.S. Virgin Islands Zika health brigade: Providing recommended pediatric health screenings for children born to mothers with laboratory evidence of possible Zika virus infection during pregnancy.

BACKGROUND: The United States Virgin Islands (USVI) Department of Health (DOH) conducted a second Zika health brigade (ZHB) in 2021 to provide recommended Zika-related pediatric health screenings, including vision, hearing, neurologic, and developmental screenings, for children in the USVI. This was replicated after the success of the first ZHB in 2018, which provided recommended Zika-related pediatric health screenings to 88 infants and children exposed to Zika virus (ZIKV) during pregnancy. METHODS: Ten specialty pediatric care providers were recruited and traveled to the USVI to conduct the screenings. USVI DOH scheduled appointments for children included in CDC's U.S. Zika Pregnancy and Infant Registry (USZPIR). During the ZHB, participants were examined by pediatric ophthalmologists, pediatric audiologists, and pediatric neurologists. We report the percentage of participants who were referred for additional follow-up care or given follow-up recommendations in the 2021 ZHB and compare these referrals and recommendations to those given in the 2018 ZHB. RESULTS: Thirty-three children born to mothers with laboratory evidence of ZIKV infection during pregnancy completed screenings at the 2021 ZHB, of which 15 (45%) children were referred for additional follow-up care. Ophthalmological screenings resulted in the highest number of new referrals for a specialty provider among ZHB participants, with 6 (18%) children receiving referrals for that specialty. Speech therapy was the most common therapy referral, with 10 (30%) children referred, of which 9 (90%) were among those who attended the 2018 ZHB. CONCLUSIONS: Thirty-three children in a jurisdiction with reduced access to healthcare specialists received recommended Zika-related pediatric health screenings at the ZHB. New and continuing medical and developmental concerns were identified and appropriate referrals for follow-up care and services were provided. The ZHB model was successful in creating connections to health services not previously received by the participants.

Zika Virus Vaccine: The Current State of Affairs and Challenges Posed by Antibody-Dependent Enhancement Reaction.

Infection caused by the Zika virus (ZIKV) can lead to serious neurological complications such as microcephaly in neonates. At present, no approved ZIKV vaccine is available, but few vaccine candidates are undergoing clinical trial. One major challenge faced is antibody-dependent enhancement (ADE) reaction that may provoke severe outcome in subsequent infection by ZIKV or other flaviviruses. Thus, more efforts should be dedicated to understanding ADE in designing a safe and effective vaccine to minimize the consequence of the potentially fatal infection's complications and to tackle potential ZIKV reemergence. This review discusses different types of ZIKV vaccine candidates that are currently underway in various stages of preclinical and clinical evaluations.