Seven-Month Analysis of Five SARS-CoV-2 Antibody Assay Results after ChAdOx1 nCoV-19 Vaccination: Significant Decrease in SARS-CoV-2 Antibody Titer

We investigated the longevity rates of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after a complete ChAdOx1 nCoV-19 vaccination, which are rare and important to estimate their efficacy and establish a vaccination strategy. We assessed the positivity rates and changes of titers before (T0) and at one month (T1), four months (T2), and seven months (T3) after a ChAdOx1 nCoV-19 vaccination using five SARS-CoV-2 antibody assays. A total of 874 serum samples were obtained from 228 (T0 and T1), 218 (T2), and 200 (T3) healthcare workers. The positive rates for all five assays were 0.0–0.9% at T0, 66.2–92.5% at T1, 98.2–100.0% at T2, and 66.0–100.0% at T3. The positive rates at T3 were decreased compared to those at T2. The median antibody titers of all the assays at T3 were significantly decreased compared to those at T2 (860.5 to 232.0 U/mL for Roche total, 1041.5 to 325.5 AU/mL for Abbott IgG, 10.9 to 2.3 index for Siemens IgG, 99.5% to 94.7% for SD Biosensor V1, and 88.5% to 38.2% for GenScript). A third-dose scheme can be considered based on our data generated from five representative assays. Our findings contribute insights into SARS-CoV-2 antibody assays and appropriate vaccination strategies.

Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis

Objectives To investigate the population pharmacokinetics of posaconazole gastroresistant tablets in children with cystic fibrosis (CF) and perform simulations to recommend optimal doses. Patients and methods Children from a paediatric CF centre who had received posaconazole tablets and underwent therapeutic drug monitoring were identified from pharmacy records. Relevant clinical data were collated from case notes and electronic patient records and used to develop an allometrically scaled population pharmacokinetic model. A stepwise covariate model-building exercise evaluated the influence of interacting medicines and liver function. Results One hundred posaconazole serum concentrations were collected from 37 children with a median age of 14 years (range 7–17). Posaconazole pharmacokinetics were adequately described by a one-compartment model with inter-individual variability on clearance. Dose simulations demonstrated a 77%–83% probability of attaining a trough target of 1 mg/L with a dose of 300 mg every 12 h for two doses then 300 mg once daily (OD) in children aged 6–11 years; and 86%–88% with a dose of 400 mg every 12 h for two doses then 400 mg OD in adolescents aged 12–17 years. This dose scheme also yielded a 90% probability of achieving an AUC of 30 mg·h/L. AUC and trough concentration were highly correlated (r2 = 0.98). Simulations showed that trough concentrations of >0.75 mg/L would exceed an AUC of 30 mg·h/L in 90% of patients. Conclusions A starting dose of 300 mg OD in those aged 6–11 years and 400 mg OD in those aged 12–17 years (following loading doses) yields a 90% probability of attaining an AUC of 30 mg·h/L.

Mumps in Poland in 2018

INTRODUCTION. Vaccination against mumps from 2003 is mandatory in Poland and given as two dose scheme with MMR vaccine (mumps, measles, and rubella). Earlier this vaccination was only recommended. Despite observed decline in mumps incidence for over a decade which is a result of conducted vaccinations, mumps is still a common disease among the children. AIM. To assess epidemiological situation of mumps in Poland in 2018, including vaccination coverage in Polish population, in comparison to previous years. METHODS. The descriptive analysis was based on data retrieved from routine mandatory surveillance system and published in the annual bulletins “Infectious diseases and poisonings in Poland in 2018” and “Vaccinations in Poland in 2018”. RESULTS. In total, there were 1 585 mumps cases registered in Poland in 2018. Incidence of mumps was 4.1 per 100,000 and it was lower in comparison with 2017. The highest incidence (6.6 per 100 000) was registered in Opolskie voivodeship and the lowest (2.6) – in Warmińsko-mazurskie voivodeship. The highest incidence rate was observed among children aged 5 years (39.2 per 100 000). Incidence in men (5.0 per 100 000) was higher than in women (3.4). In 2018, 28 people were hospitalized due to mumps. Vaccination coverage of children aged 3 years in Poland in 2018 was 92,9% and it was lower by 1.1% in comparison with year 2017. CONCLUSIONS. Systematic execution of mumps vaccination in accordance with the National Immunisation Programme resulted in a significant decrease in the number of registered cases. Due to the high vaccination coverage further decline in the number of cases is expected.

Voxel based evaluation of sequential radiotherapy treatment plans with different dose fractionation schemes

Objective: This study presents a methodology for voxel-based evaluation of two phase sequential radiotherapy treatment plans having conventional dose scheme in the first phase and subsequent hypofractionation dose scheme in the second phase based upon different priority [planning target volume (PTV), clinical target volume (CTV) and organs at risk (OAR)] of display modes. Methods: A case of carcinoma prostate was selected for demonstration. Varian Eclipse treatment planning system (TPS) was used for contouring and planning. In the first phase, a dose of 52 Gy in 26 fractions to the PTV and in the second phase, a dose of 19.5 Gy in 3 fractions to the PTV Boost was planned on the same CT data set. Both the plans (Phase 1 and Phase 2) were exported and processed using “Voxel-based radiobiology display (VRb) tool”. Plan Sum for Biologically effective dose (BED)-Cube and equivalent dose of 2Gy (EQD2)-Cube was reconstructed using a combination of linear quadratic (LQ) and linear quadratic-linear (LQ-L) radiobiological models. Tumor control probability (TCP) and normal tissue complication probability (NTCP) for different target volumes and organs were also calculated using EQD2-volume histograms of the Plan Sum. Results: An in-house graphical user interface (GUI) is developed to present the qualitative and quantitative evaluation of the multiphase treatment plans with different display modes and dose regimens. The voxel based TCP obtained for the combined target volume was 90.56%. NTCP for the bladder and rectum was calculated from the Plan Sum histograms and found to be 0.33% and ~0.0% respectively. Conclusion: The proposed methodology using the VRb tool offers superior plan evaluation for multiphase sequential radiotherapy treatment plans over the existing methods. Advances in knowledge: PTV, CTV and OAR priority based display modes in VRb tool offers better understanding of radiobiological evaluation of sequential radiotherapy treatment plans.

Mumps in Poland in 2017

BACKGROUND. Vaccination against mumps from 2003 is mandatory in Poland and given as two dose scheme with MMR vaccine (mumps, measles, and rubella). Earlier this vaccination was only recommended. Despite observed decline in mumps incidence for over a decade which is a result of conducted vaccinations, mumps is still a common disease among the children. AIM. To assess epidemiological situation of mumps in Poland in 2017, including vaccination coverage in Polish population, in comparison to previous years. METHODS. The descriptive analysis was based on data retrieved from routine mandatory surveillance system and published in the annual bulletins “Infectious diseases and poisonings in Poland in 2017” and “Vaccinations in Poland in 2017”. RESULTS. In total, there were 1 670 mumps cases registered in Poland in 2017. Incidence of mumps was 4.3 per 100,000 and it was lower in comparison with 2016. The highest incidence (5.5 per 100 000) was registered in Małopolskie voivodeship and the lowest (3.0) – in Świętokrzyskie voivodeship. The highest incidence rate was observed among children aged 6 years (32.5 per 100 000). Incidence in men (5.1 per 100 000) was higher than in women (3.6). In 2017, 37 people were hospitalized due to mumps. Vaccination coverage of children aged 3 years in Poland in 2017 was 94,0% and it was lower by 1.5% in comparison with year 2016. CONCLUSIONS. Systematic execution of mumps vaccination in accordance with the National Immunisation Programme resulted in a significant decrease in the number of registered cases. Due to the high vaccination coverage further decline in the number of cases is expected.

Immunogenicity of a Bivalent Non-Purified Recombinant Vaccine against Botulism in Cattle

Botulism is a potentially fatal intoxication caused by botulinum neurotoxins (BoNTs) produced mainly by Clostridium botulinum. Vaccination against BoNT serotypes C and D is the main procedure to control cattle botulism. Current vaccines contain formaldehyde-inactivated native BoNTs, which have a time-consuming production process and pose safety risks. The development of non-toxic recombinant vaccines has helped to overcome these limitations. This study aims to evaluate the humoral immune response generated by cattle immunized with non-purified recombinant fragments of BoNTs C and D. Cattle were vaccinated in a two-dose scheme with 100, 200 and 400 µg of each antigen, with serum sampling on days 0, 56, 120, and 180 after vaccination. Animals who received either 200 or 400 μg of both antigens induced titers higher than the minimum required by the Brazilian ministry of Agriculture, Livestock and Food Supply and achieved 100% (8/8) seroconversion rate. Animals vaccinated with commercial toxoid vaccine had only a 75% (6/8) seroconversion rate for both toxins. Animals that received doses containing 400 µg of recombinant protein were the only ones to maintain titers above the required level up until day 120 post-vaccination, and to achieve 100% (8/8) seroconversion for both toxins. In conclusion, 400 µg the recombinant Escherichia coli cell lysates supernatant was demonstrated to be an affordable means of producing an effective and safe botulism vaccine for cattle.

Policies and processes for human papillomavirus vaccination in Latin America and the Caribbean

Objectives. Three highly effective vaccines are available to prevent human papillomavirus (HPV) infection, and they have been introduced in many countries around the world. This article describes advances and challenges in introducing HPV vaccines in the Expanded Program of Immunization (EPI) of countries in Latin America and the Caribbean (LAC). Methods. We reviewed national and regional sources of information to identify LAC countries with and without universal HPV vaccination, along with the year of introduction, type of HPV vaccine, vaccination scheme, age groups targeted, and coverage level reached. Incidence rates of cervical cancer were compared across countries with and without an HPV vaccination program, in order to identify inequities in access to HPV vaccines. Results. So far, 10 LAC countries have supplied data on their vaccination policies and vaccination coverage rates to the Pan America Health Organization. The majority of those 10 started their vaccination programs using quadrivalent vaccine. Only Chile, Ecuador, and Mexico started their programs using a two-dose scheme. However, by the end of 2016, most of the other countries had switched from a three-dose to a two-dose scheme. Different age groups are targeted in the various programs. Some countries vaccinate one-year birth cohorts, while others vaccinate multiple-year birth cohorts. By the end of 2014, coverage with at least two doses ranged from a low of 2% to a high of 86%. With the exception of Venezuela, the LAC countries with the largest populations introduced universal HPV vaccination between 2010 and 2014. Despite the progress that has occurred in some LAC countries, there are still 10 LAC nations with cervical cancer rates above the LAC average (21.2 cases per 100 000) that have not introduced an HPV vaccine in their EPI.Conclusions. With several key adjustments, HPV vaccination programs across Latin America and the Caribbean could be substantially strengthened. Ongoing monitoring of HPV infection outcomes is needed in order to assess the impact of different vaccination policies.