Efficacy and feasibility of SMS m-Health for the detection of adverse events following immunisation (AEFIs) in resource-limited setting-The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomised control trial.

INTRODUCTION: The mHealth active participant centred (MAPC) adverse events following immunisation (AEFI) surveillance is a promising area for early AEFI detection resulting in risk minimisation. Passive (spontaneous) AEFI surveillance is the backbone for vaccine pharmacovigilance, but has inherent drawbacks of under reporting, and requires strengthening with active surveillance methods. AIM: The Zimbabwe stimulated telephone assisted rapid safety surveillance (Zm-STARSS) randomised controlled trial (RCT) sought to evaluate the efficacy and feasibility of AEFI detection using a short message service (SMS) and computer assisted telephone interview (CATI) approach. METHOD: A multicentre Zm-STARSS RCT enrolled consented adult vaccinees or parents or guardians of children receiving vaccines, including COVID-19 vaccines, at study vaccination clinics. At enrolment study participants were randomised to either SMS-CATI group or control group. SMS prompts were sent on days 0-2 and 14 post-vaccination to SMS-CATI group to ascertain if a medically attendance or attention due to an Adverse event following immunisation (AEFI) had occurred. However, no SMSs were sent to the control group. SMS-CATI group who responded "Yes" to SMS prompts were interviewed by research healthcare workers (RHCWs) who completed a CATI to determine if an AEFI had occurred whilst an AEFI in control group was determined from passive AEFI reporting channels. The primary study outcome was the AEFI detection rate in the SMS-CATI group compared to the control group. RESULTS: A total of 4560 participants were enrolled after signed informed consent, all were encouraged to report AEFIs and randomised automatically on 1:1 basis into two arms SMS CATI intervention group (n = 2280) and a control passive AEFI surveillance group (n = 2280) on day 0. A total of 704 (31 %) participants responded to the SMS prompts, with 75 % (528/704) indicating "No" and 25 % (176/704) reporting "Yes" to seeking medical attention or attendance post-immunisation. 69 % (121/176) completed a CATI survey but in only 36 % (44/121) was the AEFI confirmed. There were no AEFIs reported in control group participants. The detection rate of a AEFI associated with medically attendance or attention using the SMS-CATI methodology was 2 % (44/2280) on an intention to treat cohort. CONCLUSION: Despite the low SMS response and CATI completion rate, we demonstrated that Zm-STARSS SMS system improves AEFI detection compared to passive AEFI surveillance. We recommend that this and similar approaches are explored further using cost-effective multi-channel digital approaches for holistic pharmacovigilance to improve AEFI detection in Low Middle-Income Countries (LMICs) for all vaccines.

Eventos adversos supuestamente atribuibles a la vacunación e inmunización asociados a la vacuna anti-COVID-19 Sputnik V en el personbal del hospital Juan P. Garrahan / Adverse events allegedly attributable to vaccination and immunization with the anti-COVID-19 Sputnik V vaccine in the staff of the Hospital Juan P. Garrahan

Introducción: Debido a la emergencia provocada por la pandemia por el virus SARS-CoV-2 se ha producido una crisis sanitaria global. Una vez disponibles las vacunas, se espera que jueguen un rol decisivo para el control de la enfermedad. Dichas vacunas fueron desarrolladas en tiempo récord por lo que es esencial monitorear su seguridad. Durante la Campaña de Vacunación contra COVID-19, todos los Eventos supuestamente atribuibles a vacunación e inmunización (ESAVI) debieron ser notificados al Ministerio de Salud de la Nación a través del Sistema Integrado de Información Sanitaria de Argentina (SIISA). Materiales y métodos: Se realizó un estudio observacional prospectivo desde el 04/01/2021 al 05/05/2021 en el personal del Hospital Garrahan. Se utilizaron dos métodos de vigilancia de ESAVI. La vigilancia pasiva incluyó las notificaciones voluntarias recibidas de forma telefónica y a través de un cuestionario publicado en intranet. La vigilancia activa se realizó sobre los primeros 947 trabajadores inmunizados, enviando el mismo cuestionario por WhatsApp. Resultados: Hasta el día 05/05/2021 fueron inmunizados 5056 agentes, 4865 con las dos dosis. Se notificaron 473 ESAVI. De ellos, 304 correspondían a la primera dosis y 169 a la segunda. La cantidad de notificaciones según su origen fue de 136 para la vigilancia pasiva, y 333 para la vigilancia activa. Se registraron 5 ESAVI graves; tres anafilaxias, un escotoma secundario a la hipertermia generada por la vacuna y una reacción alérgica grave. Los síntomas locales más frecuentes fueron: dolor, enrojecimiento, hinchazón e induración. Los síntomas sistémicos más frecuentes fueron: fiebre, febrícula, astenia, cefalea, mialgia, artralgia y síntomas gastrointestinales. Como tratamiento en la mayoría de los casos se utilizó paracetamol. Discusión: El presente trabajo logró recolectar un número significativo de notificaciones, brindando información útil al tratarse de una vacuna recientemente aprobada en nuestro país y el mundo. (AU)

Introduction: Due to the SARS-CoV-2 pandemic emergency, a global health crisis has occurred. Once vaccines become available, they are expected to play a decisive role in controlling the disease. These vaccines were developed in record time, and therefore it is essential to monitor their safety. During the COVID-19 Vaccination Campaign, all Events Suspected to be Attributable to Vaccination and Immunization (ESAVI) had to be notified to the National Ministry of Health through the Integrated Health Information System of Argentina (SIISA). Material and methods: A prospective observational study was conducted from 04/01/2021 to 05/05/2021 in the staff of Garrahan Hospital. Two methods of ESAVI surveillance were used. Passive surveillance included voluntary notifications received by telephone and through a questionnaire posted on intranet. Active surveillance was conducted on the first 947 immunized workers, sending the same questionnaire by WhatsApp. Results: Up to 05/05/2021, 5056 workers were immunized, of whom 4865 with two doses. A total of 473 ESAVI were reported. Of these, 304 corresponded to the first dose and 169 to the second. The number of notifications was 136 for passive surveillance and 333 for active surveillance. Five severe ESAVIs were recorded; three anaphylaxis, one scotoma secondary to vaccine-generated hyperthermia, and one severe allergic reaction. The most frequent local symptoms were: pain, redness, swelling, and induration. The most frequent systemic symptoms were: mild fever or fever, asthenia, headache, myalgia, arthralgia, and gastrointestinal symptoms. Paracetamol was used as treatment in most cases. Discussion: In the present study a significant number of notifications was collected, providing useful information on a vaccine recently approved in our country and in the world (AU)

Screening for active COVID-19 infection and immunization status prior to biologic therapy in IBD patients at the time of the pandemic outbreak.

Coronavirus disease 2019 has been recently classified as pandemic infection by the World Health Organization. Patients with inflammatory bowel disease (IBD) are invited to follow the national recommendations as any other person. It is unclear whether a more aggressive clinical course might develop in asymptomatic COVID-19 infected subjects during biological therapy and current evidence does not support treatment suspension. However, during pandemic, the start of treatment with immunosuppressive drugs and biologics should be postponed whenever possible and based on an individual risk assessment. When clinical conditions and the disease activity do not allow a treatment delay, before starting a biological therapy, screening of IBD patients for COVID-19 active infection by RT-PCR should be advisable, even in absence of clinical suspicion. Serum antibody testing, when available, could provide evidence of infection as well as identify patients already immune to the disease.

[False beliefs about vaccines]. / Falsas creencias sobre las vacunas.

Vaccines are an essential tool for the prevention of infectious diseases. However, false ideas and rumours with no scientific foundation about their possible negative effects may dissuade people from being vaccinated, with the consequent risks for the health of the population. The objective of this article is to evaluate the origin and the arguments of some of the most frequent mistaken ideas and rumours about the possible adverse effects of vaccines. Some clearly established adverse effects are presented, as well as false beliefs about various vaccines and potential harm to health. Vaccines, like any drug, can cause adverse effects, but the possible adverse effects of vaccination programs are clearly lower than their individual (vaccinated) and collective benefits (those vaccinated and those who cannot be vaccinated for medical reasons). The possible adverse effects attributable to vaccines should be detected by powerful and well-structured pharmacovigilance systems.

Widespread cortical demyelination of both hemispheres can be induced by injection of pro-inflammatory cytokines via an implanted catheter in the cortex of MOG-immunized rats.

Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a few days. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats. After 14days the rats were immunized with 5µg myelin oligodendrocyte glycoprotein (MOG) in incomplete Freund's Adjuvant, which did not cause any clinical signs but animals developed a stable anti-MOG antibody titer. Then the animals received an injection of proinflammatory cytokines through the catheter. This led to a demyelination of cortical and subcortical areas starting from day 1 in a cone-like pattern spreading from the catheter area towards the subarachnoid space. On day 3 cortical demyelination already expanded to the contralateral hemisphere and reached its peak between days 9-15 after cytokine injection with a widespread demyelination of cortical and subcortical areas of both hemispheres. Clinically the animals showed only discrete signs of fatigue and recovered completely after day 15. Even on day 30 we still were able to detect demyelination in subpial and intracortical areas along with areas of partial and complete remyelination. Loss of cortical myelin was accompanied with marked microglia activation. A second injection of cytokines through the catheter on day 30 led to a second demyelination phase with the same symptoms, but again no detectable motor dysfunction. Suffering of the animals appeared minor compared to standard Experimental Autoimmune Encephalomyelitis and therefore, even long-term observation and repeated demyelination phases seem ethically acceptable.

Ginseng diminishes lung disease in mice immunized with formalin-inactivated respiratory syncytial virus after challenge by modulating host immune responses.

Formalin-inactivated respiratory syncytial virus (FI-RSV) immunization is known to cause severe pulmonary inflammatory disease after subsequent RSV infection. Ginseng has been used in humans for thousands of years due to its potential health benefits. We investigated whether ginseng would have immune modulating effects on RSV infection in mice previously immunized with FI-RSV. Oral administration of mice with ginseng increased IgG2a isotype antibody responses to FI-RSV immunization, indicating T-helper type 1 (Th1) immune responses. Ginseng-treated mice that were nonimmunized or previously immunized with FI-RSV showed improved protection against RSV challenge compared with control mice without ginseng treatment. Ginseng-mediated improved clinical outcomes after live RSV infection were evidenced by diminished weight losses, decreased interleukin-4 cytokine production but increased interferon-γ production, modulation of CD3 T-cell populations toward a Th1 response, and reduced inflammatory response. Ginseng-mediated protective host immune modulation against RSV pulmonary inflammation was observed in different strains of wild-type and mutant mice. These results indicate that ginseng can modulate host immune responses to FI-RSV immunization and RSV infection, resulting in protective effects against pulmonary inflammatory disease.

Amyloid beta immunization worsens iron deposits in the choroid plexus and cerebral microbleeds.

Anti-amyloid beta (Aß) immunotherapy provides potential benefits in Alzheimer's disease patients. Nevertheless, strategies based on Aß1-42 peptide induced encephalomyelitis and possible microhemorrhages. These outcomes were not expected from studies performed in rodents. It is critical to determine if other animal models better predict side effects of immunotherapies. Mouse lemur primates can develop amyloidosis with aging. Here we used old lemurs to study immunotherapy based on Aß1-42 or Aß-derivative (K6Aß1-30). We followed anti-Aß40 immunoglobulin G and M responses and Aß levels in plasma. In vivo magnetic resonance imaging and histology were used to evaluate amyloidosis, neuroinflammation, vasogenic edema, microhemorrhages, and brain iron deposits. The animals responded mainly to the Aß1-42 immunogen. This treatment induced immune response and increased Aß levels in plasma and also microhemorrhages and iron deposits in the choroid plexus. A complementary study of untreated lemurs showed iron accumulation in the choroid plexus with normal aging. Worsening of iron accumulation is thus a potential side effect of Aß-immunization at prodromal stages of Alzheimer's disease, and should be monitored in clinical trials.

Lymphatic dysfunction impairs antigen-specific immunization, but augments tissue swelling following contact with allergens.

The lymph transports tissue-resident dendritic cells (DCs) to regional lymph nodes (LNs), having important roles in immune function. The biological effects on tissue inflammation following lymphatic flow obstruction in vivo, however, are not fully known. In this study, we investigated the role of the lymphatic system in contact hypersensitivity (CHS) responses using k-cyclin transgenic (kCYC(+/-)) mice, which demonstrate severe lymphatic dysfunction. kCYC(+/-) mice showed enhanced ear swelling to both DNFB and FITC, as well as stronger irritant responses to croton oil compared with wild-type littermates. Consistently, challenged ears of kCYC(+/-) mice exhibited massive infiltrates of inflammatory cells. In contrast, DC migration to regional LNs, drainage of cell-free antigen to LNs, antigen-specific IFN-γ production, and lymphocyte proliferation were impaired during the sensitization phase of CHS in kCYC(+/-) mice. Transfer experiments using lymphocytes from sensitized mice and real-time PCR analysis of cytokine expression using challenged ear revealed that ear swelling was enhanced because of impaired lymphatic flow. Collectively, we conclude that insufficient lymphatic drainage augments apparent inflammation to topically applied allergens and irritants. The findings add insight into the clinical problem of allergic and irritant contact dermatitis that commonly occurs in humans with peripheral edema of the lower legs.

[Experience with use of immunomodulators in treatment of tonsillitis developed at the background of preimmunization by TEOVac].

The use of immunomodulators in the treatment of subjects with postvaccinal reactions to TEOVac was investigated. The most effective schemes were shown to be those with the use of viferon or combination of arbidol and licopide. The terms of the response signs cupping off were much shorter vs. the cases treated with polyoxidonium. The immunomodulating factors did not affect the intensity of the immunity to the vaccine virus.

Randomized clinical trial of musical distraction with and without headphones for adolescents' immunization pain.

Distraction has shown to be a helpful pain intervention for children; however, few investigations have studied the effectiveness of this method with adolescents. The aim of this study was to evaluate the usefulness of an easy and practical musical distraction in reducing adolescents' immunization pain. Furthermore, to examine whether musical distraction techniques (with or without headphones) used influenced the pain outcome. Hundred and eighteen 14-year-old adolescents, scheduled for polio immunization, participated. Adolescents were randomly assigned to one of three research groups; musical distraction with headphones (n=38), musical distraction without headphones (n=41) and standard care control (n=39). Results showed adolescents receiving musical distraction were less likely to report pain compared to the control group, controlling for covariates. Comparing musical distraction techniques, eliminating headphone emerged as a significant predictor of no pain. Results suggest that an easy and practical musical distraction intervention, implemented without headphones, can give some pain relief to adolescents during routine vaccination.

Psychological interventions for reducing pain and distress during routine childhood immunizations: a systematic review.

BACKGROUND: Immunizations are a common source of pain and distress for children. Psychological interventions consist of a variety of techniques for relaxing and distracting children during immunization with the goal of reducing pain and distress. OBJECTIVE: We conducted a systematic review to determine the efficacy of various psychological strategies for reducing pain and distress in children during routine immunizations. METHODS: MEDLINE, PsycINFO, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials databases were searched to identify randomized controlled trials (RCTs) and quasi-RCTs that determined the effect of psychological interventions on pain and distress during injection of vaccines in children 0 to 18 years of age, using validated child self-reported pain or observer-reported assessments of child distress or pain. We examined the efficacy of 7 psychological interventions: (1) breathing exercises; (2) suggestion; (3) child-directed distraction; (4) parent-led distraction; (5) nurse-led distraction; (6) parent coaching; and (7) combined cognitive-behavioral interventions. All meta-analyses were performed using a fixed-effects model. RESULTS: Twenty RCTs involving 1380 infants and children (1 month to 11 years of age) were included in the systematic review. Breathing exercises were effective in reducing children's self-reported pain (standardized mean difference [SMD], -0.43; 95% CI, -0.76 to -0.09; P = 0.01), observer-rated distress (SMD, -0.40; 95% CI, -0.68 to -0.11; P = 0.007), and nurse-reported distress (SMD, -0.57; 95% CI, -0.98 to -0.17; P = 0.005). Self-reported distress ratings appeared to be lower with breathing exercises, but the difference was not statistically significant. No evidence was found to support suggestion as a psychological intervention for reducing pain associated with pediatric immunization. Child-directed distraction was effective in reducing self-reported pain (SMD, -0.28; 95% CI, -0.54 to -0.03; P = 0.03). Parent-led distraction was effective in reducing observer-rated distress (SMD, -0.50; 95% CI, -0.82 to -0.19; P = 0.002), but not other measures of pain or distress. Nurse-led distraction was effective in reducing distress ratings as assessed by the observer (SMD, -0.40; 95% CI, -0.68 to -0.12; P = 0.005), the parent (SMD, -0.37; 95% CI, -0.66 to -0.07; P = 0.01), and the nurse (SMD, -0.42; 95% CI, -0.70 to -0.14; P = 0.004). Parent coaching was effective in reducing observer-rated distress (SMD, -0.71; 95% CI, -1.02 to -0.39; P < 0.001), but not other measures of pain or distress. Combined cognitive-behavioral interventions were effective in reducing children's self-reported pain (SMD, -0.75; 95% CI, -1.03 to -0.48; P < 0.001), observer-rated distress (SMD, -0.53; 95% CI, -0.83 to -0.23; P < 0.001), and parent-rated distress (SMD, -0.97; 95% CI, -1.37 to -0.57; P < 0.001). The methodologic quality of the included trials was generally poor, with 18 (90%) of the 20 studies rated as having a high risk of bias. CONCLUSIONS: Evidence suggests that breathing exercises, child-directed distraction, nurse-led distraction, and combined cognitive-behavioral interventions are effective in reducing the pain and distress associated with routine childhood immunizations. Although additional well-designed trials examining psychological interventions are needed, parents and health care professionals should be advised to incorporate psychological interventions to reduce the pain and distress experienced by children during immunization.

Vaccination for the paediatrician.

In most of Australia, general practitioners manage routine childhood vaccination schedules. However, paediatricians have an important role and need to have a thorough understanding of vaccination, particularly as it interfaces with other medical care. This is challenging as the Australian Standard Vaccination Schedule has undergone some substantial changes over the past 4 years, with the addition of meningococcal C conjugate, 7 valent pneumococcal conjugate, varicella and inactivated polio vaccines. Paediatricians are frequently the first port of call for advice on vaccination schedules for children with special needs, in relation to either vaccine efficacy or the risk of side effects. Categories include children with a range of chronic diseases, immunosuppression, premature infants and immigrant children. Advice about specific vaccines such as varicella, inactivated polio, influenza or multivalent vaccines and revaccination after adverse events is also often sought. The aim of this article is to update paediatricians on vaccination recommendations and relevant reference sources. The first part of this article discusses groups with special vaccination requirements. The second part discusses the use of individual vaccines in these children.

Immunizations in pregnancy. A public health perspective.

With the successful implementation of childhood immunization programs in the United States, an increasing percentage of vaccine-preventable infections now occur in adults. By providing primary care services to adult women, midwives are in a unique position to halt the spread of these infections. Immunizations are often avoided in pregnancy and the early post partum period, however, in the mistaken belief that vaccines are harmful to the fetus or neonate. This article, the first in a two-part series on immunizations, reviews the current epidemiology of vaccine-preventable diseases, discusses the indications and precautions for vaccine usage in pregnancy and the early postpartum period, and presents the current recommendations from the American Committee on Immunization Practices for the most commonly administered adult immunizations: tetanus-diphtheria, hepatitis B, influenza, pneumococcal, measles, mumps, rubella, and varicella.

Victims of our own success: will immunization remain the paradigm of effective prevention? Grantmakers In Health.

As part of its continuing mission to serve trustees and staff of health foundations and corporate giving programs, Grantmakers In Health (GIH) convened a select group of grantmakers and national experts who have made a major commitment to childhood immunization. The roundtable explored various factors influencing public acceptance of childhood immunization, with discussions ultimately centering on the importance of ensuring and conveying accurate information to the public and policymakers. Current and potential roles for health philanthropy were also discussed. This report brings together key points from the day's discussion with factual information on childhood immunization drawn from a background paper prepared for the meeting. When available, recent findings, facts, and figures have been incorporated.

Children's responses to immunizations: lullabies as a distraction.

The purpose of this study was to investigate the effects of audiotaped lullabies on physiological and behavioral distress and perceived pain among children during routine immunization. An experimental design was used to study 99 healthy children ages 3 to 6 years. Half the children received the musical intervention during the immunizations, while the other half did not. Groups were assessed during five phases: baseline, preimmunizations, during the immunization, after Band-Aid application, and 2 min after phase 4. Physiological variables (heart rate, blood pressure) were obtained in phases 1, 4, and 5. Behavioral distress was measured using the Observational Scale of Behavioral Distress during phases 1, 2, 3, and 4. Pain perception was measured using the Oucher in phases 1 and 4. No significant differences were found between experimental and control groups for heart rate, blood pressure, or Oucher scores. However, total distress scores were significantly less for the experimental group. These results indicate that immunization is a stressful experience for children. Recommendations include further study incorporating pharmacological and nonpharmacological interventions.