Dynamics and immunomodulation of cognitive deficits and behavioral changes in non-severe experimental malaria.

Data recently reported by our group indicate that stimulation with a pool of immunogens capable of eliciting type 2 immune responses can restore the cognitive and behavioral dysfunctions recorded after a single episode of non-severe rodent malaria caused by Plasmodium berghei ANKA. Here we explored the hypothesis that isolated immunization with one of the type 2 immune response-inducing immunogens, the human diphtheria-tetanus (dT) vaccine, may revert damages associated with malaria. To investigate this possibility, we studied the dynamics of cognitive deficits and anxiety-like phenotype following non-severe experimental malaria and evaluated the effects of immunization with both dT and of a pool of type 2 immune stimuli in reversing these impairments. Locomotor activity and long-term memory deficits were assessed through the open field test (OFT) and novel object recognition task (NORT), while the anxiety-like phenotype was assessed by OFT and light/dark task (LDT). Our results indicate that poor performance in cognitive-behavioral tests can be detected as early as the 12th day after the end of antimalarial treatment with chloroquine and may persist for up to 155 days post infection. The single immunization strategy with the human dT vaccine showed promise in reversal of long-term memory deficits in NORT, and anxiety-like behavior in OFT and LDT.

Effectiveness of booster dose of tetanus and diphtheria toxoids (Td) vaccine in management of recurrent aphthous stomatitis: a prospective, randomized, triple-blind and placebo-controlled clinical trial.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most common oral disease. The activation of the immune system by vaccines might reduce the interactions between oral mucosa and microorganisms. AIM: To evaluate the effect of the tetanus-diphtheria toxoids (Td) vaccine in management of RAS. DESIGN AND SETTING: This prospective, randomized, triple-blind and placebo-controlled clinical trial study was conducted on 70 eligible patients with minor RAS at the dermatology outpatient clinic. METHOD: Finally, a total of 66 participants (48 male, 18 female; mean age: 38.56 ± 10.98 years) completed the study in two groups, one in which colchicine and a single dose of vitamin B6 (placebo group) was treated and one in which colchicine and a single dose of Td vaccine (intervention group) was treated. RESULTS: After six months of follow-up, the patients were evaluated, which revealed significant effects of the Td vaccine on pain intensity, ulcer size, recovery time, and the interval between episodes. At the end of the six month follow-up, 27 patients (81.8%) in the intervention group and 13 patients (39.4%) in the placebo group showed partial or complete recovery, and there was statistically significant difference between the groups (p < .001). Recovery was not significantly associated with sex, education level, marital status and duration of RAS. However, occupation and positive family history of RAS had significant relations with recovery. CONCLUSIONS: A booster dose of Td vaccine had relatively favorable effects on pain intensity and recurrence of RAS, but further research is needed to confirm its efficacy.

Incorporation of T-cell epitopes from tetanus and diphtheria toxoids into in-silico-designed hypoallergenic vaccine may enhance the protective immune response against allergens.

OBJECTIVES: New generation of allergy vaccines is capable of promoting the development of protective IgG and blocking the functionality of allergen-specific IgE. We incorporated universal and powerful T-cell epitopes from tetanus and diphtheria toxoids (TD epitope) into recombinant Che a 2, the well-known allergic profilin of Chenopodium album, to determine its immunological properties. MATERIALS AND METHODS: The sequence and accordingly the structure of the recombinant Che a 2 was altered to generate a hypoallergenic variant (rChe a 2.rs). Moreover, TD epitope was incorporated to produce a novel vaccine that was nominated as rChe a 2.rsT.D. The effect of treatment with these variants was evaluated on the generation of allergen-specific IgG class, as well as lymphocyte proliferation in mice. Moreover, IgE-binding characteristics of the allergic patients' sera were determined by ELISA and proliferation and cytokine production was measured in T-cells. RESULTS: ELISA and dot blot revealed strong reduction of the IgE-reactivity of human sera to the variants of Che a 2 as compared to the wild-type molecule. Furthermore, Che a 2.rs and Che a 2.rsT.D induced much lower levels of IL5 and IL13 secretion from allergic patients' PBMCs in comparison to wild-type Che a 2 protein. In mice, rChe a 2.rsT.D induced high titers of Che a 2-specific IgG antibody capable of blocking IgE-binding to rChe a 2 and induced lymphocyte proliferation more potently than rChe a 2.rs. CONCLUSION: Collectively, incorporation of T-cell epitopes of tetanus and diphtheria into hypoallergenic vaccines can dramatically enhance anti-allergic immune mechanisms, particularly in poor responders.

Vaccine immune response, autoimmunity and morbidity after neonatal blood exchange transfusion.

INTRODUCTION: A blood exchange transfusion (BET) is most commonly performed to treat severe neonatal haemolytic disease. A distinct form of blood transfusion adverse reaction is transfusion-related immunomodulation. The purpose of our retrospective single-centre case-control cohort study was to investigate whether a blood exchange transfusion in the neonatal period provokes immunomodulation and affects humoral immune response to vaccination, morbidity and occurrence of autoantibodies. METHODS: Study subjects were 74 apparently healthy children, who were born at term as appropriate for gestational age and received four doses of diphtheria and tetanus toxoid vaccine. Forty-one received BET due to neonatal hemolytic disease and no other blood product afterwards, while 33 did not receive any blood products. Analysis of diphtheria, tetanus and autoimmune antibodies was performed and their medical records were analyzed for infectious, allergic, cancerous and autoimmune diseases. RESULTS: A clearly exaggerated immune response to diphtheria (1.016 IU/mL, 95% confidence interval (CI) 0.662-1.369 IU/mL vs. 0.515 IU/mL, 95% CI 0.363 to 0.626 IU/mL, P = 0.011) and slightly exaggerated immune response to tetanus vaccine (1.798 IU/mL, 95% CI 1.180-2.416 IU/mL vs. 1.036 IU/mL, 95% CI 0.398-1.673 IU/mL, P = non-specific) were observed in BET subjects. A propensity towards autoimmunity (25.8% vs. 12.5%, P = non-specific) was observed in BET subjects. However, BET in the neonatal period did not influence the occurrence of bacterial, childhood viral diseases with exception of varicella (43.9% vs. 21.2%, P = 0.040), autoimmune and cancer diseases. CONCLUSION: BET impacted humoral immune response to diphtheria and tetanus vaccine and occurrence of autoimmune antibodies, but did not affect morbidity and the occurrence of autoimmune diseases. These effects could be related to massive antigenic load of BET and an accelerated priming of immune cells and consequent immunomodulation.

Immunization rates of pneumococcal, influenza and tetanus vaccines and knowledge and attitudes of adult patients who receive inpatient treatment at hospital: Point prevalence study.

The safety of vaccines, access to health care, the level of community's knowledge and the attention of physicians play a critical role in the rate of adult vaccination. This study aims to determine the immunization rate of pneumococcal, influenza and tetanus vaccines among the patients and their knowledge and attitudes in the hospital. The study is a cross-sectional point prevalence survey. The patients who agreed to participate in the study were interviewed using a questionnaire. Patients' gender, occupation, educational status, income level and risk factors (immunosuppressed and over 65 years old) were compared with the knowledge and attitudes about vaccinations. Of the 251 participants, 51.4% were female and 48.6% were male. The self-reported vaccination rate was 3.5% for pneumococcal, 8.6% for influenza and 26.6% for tetanus. Most of the patients have knowledge about influenza vaccination (90.3%). Patients with the high education level have significantly higher knowlege about tetanus vaccination and higher rate of tetanus vaccine compared to those with low education level (p = 0.04; p = 0.006). It was found that those with higher income levels had the more pneumococcal vaccination, more knowledge on tetanus vaccination, and more attitude that tetanus vaccine is necessary compared to those with lower income level (p < 0.05). Patients without risk factors have a higher rate of tetanus vaccination compared to those with risk factors (p < 0.001). It was inferred that the high level of education and income have a positive effect on the patients vaccination rates and their knowledge and attitude.

Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

BACKGROUND/PURPOSE: A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. METHODS: Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. RESULTS: A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. CONCLUSION: The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus.

Recomendaciones de vacunación en adultos con enfermedades respiratorias: Documento de la Asociación Argentina de Medicina Respiratoria para los neumonólogos / Recommendations on Vaccination for Adults with Respiratory Diseases. Document of the Argentina Association of Respiratory Medicine for Pulmonologists

El neumonólogo de adultos acostumbra a prescribir vacunas. Este documento hecho por expertos en aspectos de la especialidad que involucran vacunar a pacientes con enfermedades respiratorias, perteneciente a la Asociación Argentina de Medicina Respiratoria, resumió la información disponible proponiendo una participación activa en la vacunación contra influenza (VAG), neumococo (VAN), pertusis y zoster. El Ministerio de Salud (MSAL) en Argentina, como el CDC y su comité de consulta sobre inmunización (ACIP) en Estados Unidos, elaboran calendarios y recomendaciones para vacunación. La ACIP recomienda la VAG a mayores de 6 meses sin contraindicaciones; el MSAL a mayores de 65 años y a quienes tengan comorbilidades (incluye enfermedades respiratorias y tabaquismo) o contacto con personas vulnerables. La clásica VAN polisacárida de 23 serotipos es recomendada para adultos con riesgo de enfermedad invasiva, incluyendo a mayores de 65 años, revacunando a los inmunosuprimidos y una única vez a los mayores de 65 que hubieran sido vacunados 5 años antes o más; la ACIP recomienda dar la VAN conjugada de 13 serotipos, más inmunogénica, secuencialmente con la polisacárida de 23, en adultos con factores de riesgo y en mayores de 65 años. Sugerimos usarla en menores de 65 con comorbilidad respiratoria. El neumonólogo debe recordar al menos 2 vacunas más: dar el refuerzo decenal contra difteria y tétanos (DT) en mayores de 18, una vez con vacuna triple acelular (difteria, pertusis y tétanos) protegiendo contra pertusis y reduciendo su transmisión. El herpes zoster produce un rash cutáneo vesicular doloroso. Uno cada 2 mayores de 85 sufrirán al menos un ataque de herpes zoster. La vacuna reduce más del 50% la incidencia y más del 60% la neuralgia post herpética; el ACIP la recomienda en mayores de 60 años. Un gran número de los pacientes con afecciones pulmonares crónicas tienen esa edad.

The pulmonologist uses to prescribe vaccines to adult patients. Experts of the Argentina Association of Respiratory Medicine who are specialists in areas involving vaccination of patients with respiratory diseases prepared this document which summarizes the available information and proposes an active prescription of the infuenza, pneumococcus, pertussis and herpes zoster vaccinations. The Ministry of Health in Argentina as the CDC and its Advisory Committee on Immunization Practices (ACIP) in the USA, made recommendations on vaccination indications and schedules. The ACIP recommends influenza vaccination to persons older than 6 months of age without any contraindication. The Ministry of Health recommends this vaccination to persons over 65 years of age, to those with morbidities (including respiratory diseases and smoking habit) and to persons in contact with high risk people. The classic 23-valent polysaccharide pneumococcal vaccine is recommended for adults at risk of invasive disease, including persons over 65 years of age. Revaccination is recommended to immunosuppressed patients and persons over 65 years of age at 5-year intervals. The ACIP recommends vaccination with the 13-valent serotypes polysaccharide pneumococcal vaccine, which is more immunogenic, sequentially with the 23-valent vaccine in adults with risk factors and over 65 years of age. We suggest this practice in patients under 65 years of age with respiratory morbidities. The pulmonologist must remember at least two other vaccines: a booster vaccination every 10 years of diphtheria and tetanus vaccine to persons over 18 years of age, and once the triple acellular vaccine (diphtheria, pertussis and tetanus) to protect against pertussis and reduce transmission. Herpes zoster (shingles) causes a painful vesicular rash; 50% of persons over 85 years suffer at least one bout of herpes zoster. The vaccine reduces more than 50% incidence and more than 60% postherpetic neuralgia. This vaccine is recommended by ACIP for persons over 60 years. In this age group there are many patients with chronic lung conditions.

Impact of a physician recommendation.

HPV vaccination has failed to achieve uptake comparable to the other adolescent-specific vaccines. Gargano et al. conducted a survey of parents of adolescents in a single Georgia county and found uptake similar to national surveys. They also found among the most commonly cited reasons for receiving vaccines a recommendation from a health care provider and among the most commonly cited reasons for not getting any of the adolescent vaccines were concerns for adverse effects. Of note, they found that the recommendation for any one vaccine had a positive effect on the uptake of other vaccines. Their findings of the importance of provider recommendations matched findings from other studies of adolescent vaccines, infant vaccines, and adult vaccines. This is despite flaws in their study including a very poor response rate (effectively 4.5%) of those surveyed and in their reporting including a lack of details of survey methods. Local surveys of vaccination have much to offer the national and local discussion about immunization delivery and how delivery should be optimized, but such surveys should use standardized approaches as well as pursue more comprehensive investigations at the local level to address the nuances national complex-cluster surveys cannot.

Seroepidemiology of tetanus in Korean adults and adolescents in 2012.

This seroepidemiologic study was performed to evaluate the immune status against tetanus in Korean adolescents and adults and to provide evidence to develop strategies for tetanus prevention. Between July 2012 and December 2012, serum samples were collected from adults and adolescents 11 years of age and older, and serum anti-tetanus IgG titers were determined using a commercial ELISA kit. Subjects were divided into six age groups: 11-20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years, and ≥61 years. The mean anti-tetanus IgG titers and tetanus seroprevalence of the age groups were compared. A total of 1193 adults and adolescents were enrolled. Mean anti-tetanus IgG titer and tetanus seroprevalence of all subjects were 1.20 ± 3.58 IU/mL and 56.4%, respectively. The mean anti-tetanus IgG titer decreased with an increase in age (p < 0.001). Tetanus seroprevalence increased from 92.0% in the 11-20 year age group to 95.7% in the 21-30 year age group, and then decreased with a further increase in age (p < 0.001). These results reflected an appropriate Td booster vaccine coverage at 11-12 years of age. However, the tetanus seroprevalence of adults older than 41 years was as low as the levels in previous studies: therefore, adults should be more encouraged to acquire decennial Td booster vaccinations recommended by the National Immunization Program.