Modeling the waning and boosting of immunity from infection or vaccination

Immunity following natural infection or immunization may wane, increasing susceptibility to infection with time since infection or vaccination. Symptoms, and concomitantly infectiousness, depend on residual immunity. We quantify these phenomena in a model population composed of individuals whose susceptibility, infectiousness, and symptoms all vary with immune status. We also model age, which affects contact, vaccination and possibly waning rates. The resurgences of pertussis that have been observed wherever effective vaccination programs have reduced typical disease among young children follow from these processes. As one example, we compare simulations with the experience of Sweden following resumption of pertussis vaccination after the hiatus from 1979 to 1996, reproducing the observations leading health authorities to introduce booster doses among school-aged children and adolescents in 2007 and 2014, respectively. Because pertussis comprises a spectrum of symptoms, only the most severe of which are medically attended, accurate models are needed to design optimal vaccination programs where surveillance is less effective. (C) 2020 The Authors. Published by Elsevier Ltd

The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery

Objective: The aim of this study was to explore inflammatory response and identify early potential biomarkers in mid-trimester amniotic fluid associated with subsequent spontaneous preterm delivery (PTD). Methods: A cohort study was performed at Sahlgrenska University Hospital/ 6stra, Gothenburg, Sweden, between 2008 and 2010. Amniotic fluid was collected from consecutive women undergoing mid-trimester transabdominal genetic amniocentesis at 14–19 gestational weeks. Clinical data and delivery outcome variables were obtained from medical records. The analysis included 19 women with spontaneous PTD and 118 women who delivered at term. A panel of 26 candidate proteins was analyzed using Luminex xMAP technology. Candidate protein concentrations were analyzed with ANCOVA and adjusted for plate effects. Results: The median gestational age at delivery was 35 + 3 weeks in women with spontaneous PTD and 40 + 0 weeks in women who delivered at term. Nominally significantly lower amniotic fluid levels of adiponectin (PTD: median 130,695 pg/mL (IQR 71,852–199,414) vs term: median 185,329 pg/mL (IQR (135,815–290,532)), granulocyte-macrophage colony stimulating factor (PTD: median 137 pg/mL (IQR 74–156) vs term: median 176 pg/mL (IQR 111–262)), and macrophage migration inhibitory factor (PTD: median 3025 pg/mL (IQR 1885–3891) vs term: median 3400 pg/mL (IQR 2181–5231)) were observed in the spontaneous PTD group, compared with the term delivery group, after adjusting for plate effects. No significant differences remained after Bonferroni correction for multiple comparisons. Conclusions: Our results are important in the process of determining the etiology behind spontaneous PTD but due to the non-significance after Bonferroni correction, the results should be interpreted with caution. Further analyses of larger sample size will be required to determine whether these results are cogent and to examine whether microbial invasion of the amniotic cavity or intra-amniotic inflammation occurs in asymptomatic women in the mid-trimester with subsequent spontaneous PTD

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Formulación de un agente pigmentante a base de carotenoides extraídos de cascarilla comercial de rosa mosqueta (Rosa rubiginosa) para su uso en alimentos

Dada la importancia de los carotenoides como colorantes naturales además de su acción biológica en la salud humana, la cascarilla de rosa mosqueta, rica en estos pigmentos, se proyecta en su uso como materia prima en la elaboración de agentes pigmentantes naturales en la industria alimentaria. El objetivo de este trabajo consistió en preparar un agente pigmentante en polvo dispersable en agua a partir de los carotenoides extraídos de la cascarilla comercial de rosa mosqueta, estudiar su estabilidad y aplicarlo como colorante en yogurt natural. El agente pigmentante en polvo se obtuvo por la encapsulación de una oleorresina de carotenoides en dos matrices protectoras: matriz almidón/sacarosa (A) y matriz gelatina/sacarosa (G). Para esto, la oleorresina fue dispersada en una suspensión coloidal, homogenizada a presión y posteriormente la emulsión formada fue alimentada a un secador spray. La estabilidad de los pigmentos encapsulados durante la oxidación en almacenamiento a temperaturas entre 25ºC y 55ºC en oscuridad y presencia de aire, fue determinada por las características de la matriz protectora y la temperatura. La degradación de los pigmentos describió cinéticas de pseudo primer orden, donde la estabilidad de trans-rubixantina, trans-licopeno y trans-β-caroteno fue similar. La matriz G presentó valores superiores de vida media calculados a 21ºC. De igual forma, la retención de los carotenoides al final del período de almacenamiento en yogurt encapsulados en la matriz G fue superior alcanzando un 60% rubixantina y un 94% en licopeno y β-caroteno.Due the importance of the carotenoids as natural pigments, in addition to its biological action on human health, the rose hips, can be considered as a good natural source of pigments for the Food Industry. The purpose of this work was to prepare a water-dispersable powder from the carotenoids obtained from commercial rose hips, to study its stability and to use them as a natural colouring matter for natural yogurt. The powder was obtained by encapsulating a carotenoid oleoresin in two protective matrices: starch-sucrose (A) and gelatin/sucrose (G). The oleoresin was dispersed as a coloidal suspension, homogenized by pressure to get an emulsion, and then to feed into the spray-drier. The stability of the encapsulated pigments during the process of oxidation in conditions of dark storage, at 25 to 55ºC and in presence of air, was established by the features of the protective matrix and the temperature. The pigment decay presented pseudo first order kinetics, where the stability of trans-rubixantine, trans-lycopene and tras-β-carotene was comparable. The G matrix presented higher half-life values calculated at 21ºC. In the same way, the retention of the carotenoids at the end of the storage period of yogurt encapsulated in the G Matrix was high, reaching a 60% for rubixantine and 94% for lycopene and β-carotene

Evaluation of vaccines in infancy. With special reference to Haemophilus influenzae type B conjugates

During the 1990s, two new vaccines have been introduced in the national Swedish vaccination programme; Haemophilus influenzae type b (Hib) conjugate vaccine in 1993 and acellular pertussis vaccine in 1996. In the pre-vaccination era, Hib caused nearly 50% of all cases of bacterial meningitis in children, and almost all cases of acute epiglottitis. Already in 1994, a dramatic decline in the incidence of invasive Hib disease was noted and after 1996 also in the incidence of pertussis.The immunogenicity and safety of vaccines against Hib, diphtheria, tetanus, polio and pertussis, administered to 669 Swedish infants, were evaluated in three vaccination studies. The trials involved 2,085 scheduled vaccination visits and 2,340 blood sampling visits. The aims were to compare two Hib conjugate vaccines, Hib conjugated to tetanus toxoid (Hib-T) or a meningococcal outer membrane protein (Hib-OMP), to evaluate the antibody response to the tetanus toxoid component of Hib-T, to study the influence of a concurrent dose of the tetanus toxoid on the Hib antibody response of Hib-T, to compare administration routes and to compare a 3-5-12 month schedule with a 2-4-6-13 month schedule. Serum antibodies against all vaccine components were analysed and adverse reactions were monitored. In two additional studies the natural acquisition of serum antibodies to Hib and to two components, FHA and pertactin, included in some aP vaccines, were followed from infancy to school age. Serum levels of Hib antibodies of the IgG1, IgG2 and IgG4 subclasses in non-vaccinated healthy children were compared with those in children vaccinated in infancy with a Hib conjugate vaccine.The tetanus toxoid component of Hib-T induced functional antibodies against tetanus, but at a lower magnitude than the ordinary tetanus toxoid vaccine. The two Hib conjugates induced lower than expected concentrations of Hib antibodies after the first two injections, but the proportions of infants with antibodies above proposed protective level were satisfactory. The antibody response to the booster dose of Hib-T was excellent, demonstrating a good priming effect from the first two doses. Mixing of Hib-T with diphtheria, tetanus, polio and aP vaccines did not negatively influence the Hib antibody response, and a concurrent dose of tetanus toxoid did not enhance the Hib antibody response to Hib-T. The concentrations of antibodies to the other antigens were good and similar also when the vaccines differed in antigen amounts. The concentrations of antibodies against all vaccine components were lower after two than after three primary dosese, but were equally high after the booster dose. Subcutaneous administration of vaccines did not affect the antibody responses, but caused more local reactions than intramuscular administration. The adverse reactions were mild and well tolerated. In summary, the trials documented the use of the vaccines and combinations tested in the present Swedish national vaccination programme, with adequate immune responses from all components in the 3-5-12 months schedule. The immunogenicity of the protein carrier may become of clinical significance in future programmes, likely to include new conjugate vaccines under developmentPre-school children with no pertussis infection or vaccination had acquired low levels of antibodies against FHA and pertactin. It remains unclear whether or not natural acquisition of such antibodies can contribute to protection. Children vaccinated in infancy with a Hib conjugate had similar concentrations of different Hib IgG subclasses at six years of age as compared to non-vaccinated healthy controls, who by this age normally have acquired protective Hib antibodies naturally, indicating that a Hib conjugate given during the first year of life confers protection until acquisition of a natural immunity

Shifts of Bordetella pertussis Variants in Sweden from 1970 to 2003, during Three Periods Marked by Different Vaccination Programs

The Swedish population of Bordetella pertussis strains was characterized from 1,247 isolates covering a whole-cell vaccine program up to 1979, a 17-year period without vaccination (1979 to 1996), and a period after the introduction of general vaccination among newborns with acellular pertussis vaccines (1997 to 2003). Strains were characterized by serotyping and genotyping of pertactin and ptxA and by means of pulsed-field gel electrophoresis (PFGE). With emphasis on vaccine-related markers, the vast majority of circulating strains were of nonvaccine type. There were shifts of serotype connected with shifts of vaccination program. Serotype Fim3 was most frequent during the periods with general vaccination schedules, whereas serotype Fim2 was predominant during the 17-year vaccine-free period. Pertactin 1 was predominant during the pertussis whole-cell (Pw) vaccine period but was thereafter replaced by prn2 and has not reappeared after the introduction of acellular pertussis (Pa) vaccines. ptxA (1) was predominant over all three decades. There was a significant difference in the distribution of serotypes between vaccinated and unvaccinated individuals, but not for pertactin. A few PFGE profiles were predominant over the years: BpSR25 (serotype Fim3 prn1/7) and BpSR18 (serotype Fim3 prn2) during the Pw period, BpSR1 (serotype Fim2 prn2) during the 17 years without general vaccination, and BpSR11 (serotype Fim3 prn2) after the reintroduction of general vaccination in 1996. Despite differences between the pertactin and toxin types of Pa vaccines and circulating strains, there is no evidence that there is a threat, i.e., the vaccination program so far has been effective against whooping cough, and there seems to be no impact on the effectiveness of the vaccination program from the bacterial polymorphism