Immune profile of children diagnosed with multisystem inflammatory syndrome associated with SARS-CoV-2 infection (MIS-C).

Introduction: The pathophysiology of multisystem inflammatory syndrome associated with SARS-CoV-2 infection (MIS-C) remains poorly understood. This study aimed to define peripheral blood immune features in patients with MIS-C. Material and methods: We analyzed seven children diagnosed with MIS-C between April 1 and May 15, 2021, in St. Joseph's Children's Hospital in Poznan (Poland). Results: All patients had elevated inflammatory markers, IgG antibodies against SARS-CoV-2, and lymphopenia with a marked decrease in CD4+ and CD8+ T cells. The majority of CD4+ T cells were naive cells. Almost all (6/7) of the analyzed patients had a higher CD4+/CD8+ T cell ratio than average values. B cells were within the normal range - the majority were non-memory cells. Conclusions: Children with MIS-C do not resemble adults during COVID-19 recovery. The immune profile of the studied patients differs from that of children with Kawasaki disease (KD), but it is similar to that of adults with severe COVID-19. The proposed explanation is a profound lymphopenia caused by SARS-CoV-2 infection - which persists for weeks - as a result leading to uncontrolled inflammation. In COVID-19 patients the T cell level returns to normal after the second week of the disease. Our data suggest that in children prolonged lymphopenia after COVID-19 can be a practical marker for possible MIS-C alert. If there is a continuum from lymphopenia to MIS-C, there is room for screening and prevention. Further studies are needed to determine whether steroid treatment introduced in a child with prolonged lymphopenia could stop the inflammatory process.

Hypomagnesemia is underestimated in children with HNF1B mutations.

BACKGROUND: Hypomagnesemia in patients with congenital anomalies of the kidneys and urinary tract or autosomal dominant tubulointerstitial kidney disease is highly suggestive of HNF1B-associated disease. Intriguingly, the frequency of low serum Mg2+ (sMg) level varies and is lower in children than in adults with HNF1B mutations that could be partially due to application of inaccurate normal limit of sMg, irrespective of age and gender. We aimed to re-assess cross-sectionally and longitudinally the frequency of hypomagnesemia in HNF1B disease by using locally derived reference values of sMg. METHODS: Fourteen children with HNF1B-associated kidney disease were included. Control group comprising 110 subjects served to generate 2.5th percentiles of sMg as the lower limits of normal. RESULTS: In both controls and patients, sMg correlated with age, gender, and fractional excretion of Mg2+. In girls, sMg concentration was higher than in boys when analyzed in the entire age spectrum (p < 0.05). In HNF1B patients, mean sMg was lower than in controls as compared with respective gender- and age-specific interval (p < 0.001). Low sMg levels (< 0.7 mmol/l) were found in 21.4% of patients at diagnosis and 36.4% at last visit, which rose to 85.7% and 72.7% respectively when using the age- and gender-adjusted reference data. Similarly, in the longitudinal observation, 23% of sMg measurements were < 0.7 mmol/l versus 79.7% when applying respective references. CONCLUSIONS: Hypomagnesemia is underdiagnosed in children with HNF1B disease. sMg levels are age- and gender-dependent; thus, the use of appropriate reference data is crucial to hypomagnesemia in children.

The use of antibiotics in the treatment of pediatric varicella patients: real-world evidence from the multi-country MARVEL study in Latin America & Europe.

BACKGROUND: Varicella is a highly contagious childhood disease. Generally benign, serious complications necessitating antibiotic use may occur. The objective of this study was to characterize the rate, appropriateness and patterns of real-world antibiotic prescribing for management of varicella-associated complications, prior to universal varicella vaccination (UVV) implementation. METHODS: Pooled, post-hoc analysis of 5 international, multicenter, retrospective chart reviews studies (Argentina, Hungary, Mexico, Peru, Poland). Inpatient and outpatient primary pediatric (1-14 years) varicella cases, diagnosed between 2009 and 2016, were eligible. Outcomes, assessed descriptively, included varicella-associated complications and antibiotic use. Three antibiotic prescribing scenarios were defined based on complication profile in chart: evidence of microbiologically confirmed bacterial infection (Scenario A); insufficient evidence confirming microbiological confirmation (Scenario B); no evidence of microbiological confirmation (Scenario C). Stratification was performed by patient status (inpatient vs. outpatient) and country. RESULTS: Four hundred one outpatients and 386 inpatients were included. Mean (SD) outpatient age was 3.6 (2.8) years; inpatient age was 3.1 (2.8) years. Male gender was predominant. Overall, 12.2% outpatients reported ≥1 infectious complication, 3.7% ≥1 bacterial infection, and 0.5% ≥1 microbiologically confirmed infection; inpatient complication rates were 78.8, 33.2 and 16.6%, respectively. Antibiotics were prescribed to 12.7% of outpatients and 68.9% of inpatients. Among users, ß-lactamases (class), and clindamycin (agent), dominated prescriptions. Scenario A was assigned to 3.9% (outpatients) vs 13.2% (inpatients); Scenario B: 2.0% vs. 6.0%; Scenario C: 94.1% vs. 80.8%. CONCLUSIONS: High rates of infectious complications and antibiotic use are reported, with low rates of microbiological confirmation suggesting possible antibiotic misuse for management of varicella complications.

Varicella in Poland: economic burden in children 1-12 years of age in Poland, 2010-2015.

BACKGROUND: The safety and efficacy of live-attenuated varicella zoster virus (VZV) vaccines in preventing varicella and reducing associated morbidity and mortality in real-world have been previously shown. In Poland, VZV vaccination is only mandatory for certain high-risk individuals. Here, we have conducted an evaluation of the clinical and economic burden of varicella in Poland. METHODS: Multicenter, retrospective chart review of varicella inpatients and outpatients aged 1-12 years with a primary diagnosis between 2010 and 2015. Varicella-related outcomes included the incidence of complications, the proportion of patients reporting healthcare resource utilization (HCRU), and frequency of HCRU. Direct costs were derived from per patient resource use multiplied by unit costs, and indirect costs were calculated as loss of revenue of caregivers reporting work days missed. The overall annual cost of varicella in Poland was estimated based on the calculated direct and indirect costs per case and the estimated number of varicella cases. All costs are presented in 2015 Polish zloty (PLN) / Euros (€). RESULTS: A total of 150 children with varicella were included, of which 75 were outpatients and 75 were inpatients with a mean (± SD) age of 3.9 (±2.6) and 4.2 (±2.3) years, respectively. Complications were experienced by 14.7% of outpatients and 82.7% of inpatients, of which the most common were skin and soft tissue infections and dehydration. The rate of HCRU was as follows: over-the-counter medications (80.0% outpatients, 81.3% inpatients), prescription medications (80.0% outpatients, 93.3% inpatients), tests/procedures (0.0% outpatients, 69.3% inpatients), and allied health professional consults (0.0% outpatients, 24.0% inpatients). Total (direct and indirect) cost per varicella case was 5013.3 PLN (€ 1198.1) for inpatients and 1027.2 PLN (€ 245.5) for outpatients, resulting in an estimated overall annual (2015) cost of varicella in Poland of 178,198,320 PLN (€ 42,588,385) among children aged 1-15 years. CONCLUSIONS: Significant clinical and economic burden is associated with varicella in Poland. These results may be used to foster discussion related to the implications of implementing routine VZV vaccination in Poland.

Preventing congenital toxoplasmosis - implementation of clinical practice guidelines.

OBJECTIVES: The aim of the study was to evaluate obstetric care of pregnant women with regard to prevention of congenital toxoplasmosis. Additionally, we attempted to determine the frequency of markers for past infection with Toxoplasma gondii in order to characterize the current significance of preventive measures in the Polish population. MATERIAL AND METHODS: The analysis of the medical records - pregnancy charts of women who presented for delivery - was performed. Patient age, place of residence, and toxoplasmosis test (or lack of it) were evaluated. Also, further diagnostic management, depending on the serologic result, was investigated. RESULTS: Out of 670 pregnant women, 628 (93.73%) underwent at least one toxoplasmosis diagnostic test. Out of those, 502 (73%) had a negative result (IgG -, IgM -), and 2 (0.32%) had a positive result (IgG +, IgM +), while history of infection with Toxoplasma gondii was confirmed (IgG +, IgM -) in 124 (19.75%) cases. Repeat testing was required in 183 (29.14%) out of the 628 women. CONCLUSIONS: A high rate of women in whom IgG antibodies were not detected in the first test and a low rate of women who required repeat testing later in pregnancy are noteworthy. Regardless of the healthcare policy, parents should receive reliable information about the nature of the disease and possibilities of prevention, while medical professionals ought to have easy access to research data about the epidemiologic status and recommendations.

Is one minute enough to convince parents to vaccinate their child?

INTRODUCTION: A growing number of parents refuse childhood vaccination. This situation may be caused by many reasons, but surely the lack of parental knowledge is one of them. A physician, as the most reliable source of information about vaccination, plays an important role in parental education. How can we successfully inform parents about vaccinations, when faced with primary care visit being too short? The aim of this study was to assess the impact of three types of information about pneumococcal vaccine on parental decision-making. MATERIAL AND METHODS: The children were enrolled based on the inclusion and exclusion criteria. The parents received one of three types of vaccination information: simple oral, extent oral and written one. The endpoint of the study was the length of time between the day parents were informed by physician and the day first dose of vaccine was administered. RESULTS: The percentage of vaccinated children was: 12.8% for written information, 14.7% for extended and 20.8% for simple one. The simple information was significantly associated with increased chances for vaccination in the following groups: children with a birth weight <3355 g (p<0.025), born with a gestational age <40 weeks (p<0.015) and in the group with lower healthcare utilization (p<0.020). The extended information was significantly associated with increased chances for vaccination in the group of chronically ill mothers (p<0.045). CONCLUSIONS: Physicians should provide parents with personalized immunization information. One minute may be sufficient to convince parents to vaccinate their child, especially if healthcare utilization of family is low. Chronically ill parents should be given extended information. Discussion about vaccinations with parents should not be replaced by written vaccination information.

Varicella - a potential threat to maternal and fetal health.

OBJECTIVES: The aim of the study was to evaluate the following: i) number of midwives and nurses at risk for contracting varicella; ii) effectiveness of infectious disease prevention among healthcare personnel; iii) attitude of healthcare person-nel towards immunization. MATERIAL AND METHODS: A total of 524 midwives and nurses from obstetric, neonatal, and pediatric wards were investigated. Quantitative data analysis was performed. RESULTS: Overall, 14.7% potentially seronegative respondents were identified. Out of those with a positive history of varicella, 6.56% contracted the disease after starting work, and > 70% had contact with the varicella-zoster virus. Overall, 9.54% of the respondents had a history of varicella, 3.12% were informed about the possibility of immunization, and 1.56% of those with a negative history of the disease were offered a state-funded vaccine. In the same group, the number of vaccinated people amounted to 13.28%, and 26.13% would accept a state-funded vaccine. CONCLUSIONS: Varicella may constitute a significant threat to maternal and fetal health at obstetric, neonatal, and pediatric wards, which must be considered when providing care to women in the reproductive age. Occupational health physicians should confirm the immunity status of the patients and suggest immunization to seronegative subjects. Regular workshops are necessary to update the knowledge of medical professionals and patients in order to shape their attitudes and beliefs about immunization.

Polish consensus guidelines on the use of acyclovir in the treatment and prevention of VZV and HSV infections.

A physician has to perform a benefit-risk assessment each time acyclovir is prescribed "off label" for children. A group of Polish infectious disease experts was created to develop evidence-based guidelines on the use of acyclovir in the treatment and prevention of varicella zoster and herpes simplex infections. In primary varicella zoster virus infections, oral acyclovir treatment is recommended in children over 12 years of age and should be considered in younger children who fall into one of the groups at risk of severe varicella. Intravenous acyclovir therapy in varicella is recommended in patients with immune deficiencies, newborns and in complicated cases. When there is a justified need for prevention of varicella, oral acyclovir prophylaxis may be considered if immunoglobulin cannot be administered, and if it is too late for vaccination. Oral acyclovir treatment of herpes zoster may be beneficial to otherwise healthy patients with a rash in places other than the trunk and in patients over 50 years of age. In immunocompetent patients with herpes simplex infections, indications for treatment with oral acyclovir include primary (genital herpes, skin herpes in children with atopic dermatitis, ocular herpes simplex, severe gingivostomatitis, paronychia and pharyngitis) and recurrent infections. Intravenous acyclovir should be administered for herpes infections in neonates, immunocompromised patients and patients who develop complications including neurological.

Clinical presentations of Wilson disease among Polish children.

INTRODUCTION: Wilson disease (WD) may present from early childhood up to the eighth decade, presenting with variable hepatic and neuropsychiatric symptoms. Establishing the diagnosis is straightforward if the major clinical and laboratory features are present. However, clinical phenotypes are highly varied and early, proper diagnosis can be challenging. AIM: The aim of our study was to analyze clinical presentations and diagnostic tests of Polish pediatric patients with WD. METHODS: We retrospectively analyzed medical history of 156 patients with confirmed diagnosis of WD treated at our Institute from 1996 till March 2016. RESULTS: The mean age at onset of symptoms was 10.15±4.23 years of age. Hepatic presentation was the most common one (94.23%) with either liver failure (16.03%) or more frequently increased transaminases (78.2%). In 90.26% cases ceruloplasmin serum concentration was ≤0,2 g/l, in 51.93% patients basal urinary copper excretion was >100 µg/24 h. Mutation analysis was performed in 155 (99.36%) cases. The most common mutation was p.H1069Q. CONCLUSIONS: Wilson disease can present with only significantly increased transaminases activity and hepatomegaly or liver failure, but neurological symptoms are very rare in children. Diagnostic approach is challenging due to wide spectrum of clinical presentations in a high variable degree of severity. Genetic screening is supportive, ceruloplasmin and urinary copper excretion are valuable tests in the majority of patients but do not allow to exclude WD.

Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still's disease.

A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23rd day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still's disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision.

Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial.

BACKGROUND: Rates of varicella have decreased substantially in countries implementing routine varicella vaccination. Immunisation is possible with monovalent varicella vaccine or a combined measles-mumps-rubella-varicella vaccine (MMRV). We assessed protection against varicella in naive children administered one dose of varicella vaccine or two doses of MMRV. METHODS: This study was done in ten European countries with endemic varicella. Healthy children aged 12-22 months were randomised (3:3:1 ratio, by computer-generated randomisation list, with block size seven) to receive 42 days apart (1) two doses of MMRV (MMRV group), or (2) MMR at dose one and monovalent varicella vaccine at dose two (MMR+V group), or (3) two doses of MMR (MMR group; control). Participants and their parents or guardians, individuals involved in assessment of any outcome, and sponsor staff involved in review or analysis of data were masked to treatment assignment. The primary efficacy endpoint was occurrence of confirmed varicella (by detection of varicella zoster virus DNA or epidemiological link) from 42 days after the second vaccine dose to the end of the first phase of the trial. Cases were graded for severity. Efficacy analyses were per protocol. Safety analyses included all participants who received at least one vaccine dose. This trial is registered with ClinicalTrials.gov, number NCT00226499. FINDINGS: Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. In the efficacy cohort of 5285 children, the mean duration of follow-up in the MMRV group was 36 months (SD 8·8), in the MMR+V group was 36 months (8·5) and in the MMR group was 35 months (8·9). Varicella cases were confirmed for 37 participants in the MMRV group (two moderate to severe), 243 in the MMR+V group, and 201 in the MMR group. Second cases occurred for three participants (all in the MMR+V group). Varicella cases were moderate to severe for two participants in the MMRV group, 37 in the MMR+V group (one being a second case that followed a mild first case); and 117 in the MMR group. Efficacy of two-dose MMRV against all varicella was 94·9% (97·5% CI 92·4-96·6), and against moderate to severe varicella was 99·5% (97·5-99·9). Efficacy of one-dose varicella vaccine against all varicella was 65·4% (57·2-72·1), and against moderate to severe varicella (post hoc) was 90·7% (85·9-93·9). The most common adverse event in all groups was injection-site redness (up to 25% of participants). Within 15 days after dose one, 57·4% (95% CI 53·9-60·9) of participants in the MMRV group reported fever of 38°C or more, by contrast with 44·5% (41·0-48·1) with MMR+V, and 39·8% (33·8-46·1) with MMR. Eight serious adverse events were deemed related to vaccination (three MMRV, four MMR+V, one MMR). All resolved within the study period. INTERPRETATION: These results support the implementation of two-dose varicella vaccination on a short course, to ensure optimum protection from all forms of varicella disease. FUNDING: GlaxoSmithKline Vaccines.

Vaccine-Derived Immunity in Children With Cancer-Analysis of Anti-Tetanus and Anti-Diphtheria Antibodies Changes after Completion of Antineoplastic Therapy.

BACKGROUND: Cancer survival rates and longevity of patients after therapy have significantly improved during the last decades. Thus durable protection against infections should be provided. The aim of the study was to compare the levels of vaccine-derived antibodies in children with cancer compared to those of healthy children and to investigate how therapy influences the levels of specific antibodies. PROCEDURE: A group of 40 children, diagnosed with acute lymphoblastic leukemia (ALL) or solid tumor (ST), followed in Poznan University of Medical Sciences Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, were recruited for evaluation of humoral immunity. Antibody levels were checked before treatment and 3, 6, and 12 months after treatment. RESULTS: In patients with ALL or ST, levels of IgG against tetanus and diphtheria were significantly lower than in the control group. Among ALL patients, 9% remained negative for tetanus and diphtheria antibodies 12 months after therapy. Among patients with ST 3 months after chemotherapy, there were no protective antibodies in 12% against tetanus, and in 18% against diphtheria. All patients reconstituted immunity 6 and 12 months after therapy. CONCLUSIONS: Our data show that a considerable number of cancer patients lose immunity against diphtheria and tetanus after therapy. Compared to ST, patients with ALL lose protective antibody levels more often. Patients with ST reconstituted antibodies after the treatment cessation, while levels in ALL patients remained low.

Pneumocystis pneumonia in children - the relevance of chemoprophylaxis in different groups of immunocompromised and immunocompetent paediatric patients.

INTRODUCTION: Pneumocystis jirovecii is an opportunistic pathogen causing pneumocystis pneumonia (PCP), a life-threatening infection, in immunocompromised patients. In this study, retrospective analysis of the presence of P. jirovecii DNA in different samples collected from children with suspected PCP was carried out. MATERIAL AND METHODS: Three hundred and six specimens [152 bronchoalveolar lavage (BAL) specimens, 80 blood specimens, 18 bronchial secretions (BS), 34 induced sputum samples, 10 endotracheal aspirates (ETA), and 12 other type samples] obtained from patients with suspected PCP were examined by real-time PCR. RESULTS: Forty (13.1%) patients were positive for P. jirovecii: 4 (7.7%) patients with malignancies, 3 (6.8%) transplant recipients, 15 (23.1%) other immunocompromised patients, and 18 (12.4%) immunocompetent patients. Pneumocystis jirovecii DNA was detected in 20.4% of BAL specimens, 11.1% of BS samples, 10% of ETA sample, 8.8% of induced sputum samples, and in 3.7% of blood samples. Comparing the frequency of the presence of P. jirovecii DNA between the group of children treated with PCP chemoprophylaxis (malignancy patients and transplant recipients) and a group of children not receiving this prophylaxis (other immunocompromised and immunocompetent children), we found that the occurrence of PCP was twice as high in the latter group of children (7.3% and 15.7%, respectively). CONCLUSIONS: Respiratory samples, such as BS, BAL, or ETA specimens, are the material of choice for the diagnosis of PCP. Due to high incidence of PCP in certain groups of immunocompetent and immunocompromised patients, besides cancer patients and transplant recipients, consideration of PCP prophylaxis is required in these groups as well.

Patient satisfaction with primary health care rendered by community midwives in the area of Poznan.

OBJECTIVES: The main objective of this study was to examine the level of patient satisfaction with the care rendered by community midwives in the area of Poznan. MATERIAL AND METHODS: A patient survey was distributed using face-to-face recruitment and with mail collection. Eight hundred new mothers were asked to participate in the study by filling out the questionnaire after eight weeks of the postpartum period. One hundred seventy seven (22.12%) returned completed questionnaires which were then analyzed. RESULTS: This paper provides information on the high level of patient satisfaction with the services provided by community midwives and the important role community midwives play in caring for and supporting women in the post partum period. CONCLUSIONS: The results of this study indicate that women in the area of Poznan, are satisfied with the care they receive from midwives. They also indicate a lack of association of patient satisfaction scores between groups of patients based on demographic data and reason for using community midwife services. It was also found that the overall patient satisfaction score depends most heavily on the time frame of receiving community midwife services.

Epidemiology of Respiratory Syncytial Virus Hospitalizations in Poland: An Analysis from 2015 to 2023 Covering the Entire Polish Population of Children Aged under Five Years.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of childhood hospitalizations. The aim of the study was to estimate the rates of RSV-related hospitalizations in children aged less than 5 years in Poland. METHODS: This retrospective observational cohort study was based on data obtained from the National Health Fund in Poland regarding all acute respiratory tract infections and RSV-coded admissions of children (age < 5 years) to public hospitals between July 2015 and June 2023. Patients were stratified based on the following age groups: 0-1 month, 2-3 months, 4-6 months, 7-12 months, 13-24 months, and 25-60 months. RESULTS: The number of RSV-related hospitalizations increased every season, both before and through the ending phase of the coronavirus disease 2019 (COVID-19) pandemic. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infection. Hospitalization rates per 1000 inhabitants were the highest for children aged 0-12 months, reaching 47.3 in the 2022/23 season. Within this group, the highest hospitalization rate was observed for children aged 2-3 months-94.9 in the 2022/23 season. During the ending phase of the COVID-19 pandemic, the observed increase in admission rates was 2-, 4-, and 5-fold the pre-COVID rate for children aged <12 months, 12-24 months, and 25-60 months, respectively. CONCLUSIONS: In Poland, RSV infections cause a significant burden in hospitalized children aged less than 5 years. RSV-related hospitalizations were most frequent in children aged less than 1 year. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infections. After the pandemic, more RSV-related hospitalizations were observed in older children (aged 13 months and older) vs. the pre-pandemic phase.

Phase 3 Safety and Immunogenicity Study of a Three-dose Series of Twenty-valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers.

BACKGROUND: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. METHODS: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. RESULTS: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. CONCLUSIONS: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.

Improving Vaccine Assessment Pathways and Decision Making in the Polish Immunization Program.

This study examines the vaccine market access pathway in Poland to evaluate its efficiency and propose recommendations for its improvement. The research spans a comprehensive analysis of the vaccine assessment process, ranging from pre-registration to sustainability, encompassing critical components such as national immunization technical advisory groups (NITAGs), health technology assessments, resource evaluations, and decision making. This investigation utilizes a multi-phase approach. Initial desk research aimed to collect accumulated evidence about each step of the vaccine access pathway. This constituted the background for an expert panel discussion (n = 13) and a final online questionnaire (n = 12), evaluating the timeframes, inclusiveness, transparency, and consistency of the elements of the process. Poland is a late adopter of new vaccines. The country faces budget constraints and lacks a formalized framework for the inclusion of vaccines into the national immunization program. Notably, NITAGs play a crucial role, yet their limited resources and dependence on public health stakeholders diminish their impact. A formal and well-supported advisory body may become a foundation for decision-making processes. The health technology assessment conducted by the national agency is recognized for its timeliness and transparency, though the absence of fiscal analyses in vaccine assessments is identified as a gap that limits the understanding of the value of vaccinations. Resources are key drivers of decision making, and recent changes in legislation offer increased flexibility in financing vaccines. Challenges in the procurement process include a limited consideration of non-acquisition costs and an increased absence of a documented general strategy for immunization program development in Poland, pointing to a need for strategic planning. In conclusion, this study recommends the establishment of a robust NITAG with enhanced resources, incorporating fiscal analyses, transparent resource allocation, and strategic planning for immunization program development. Addressing these recommendations is crucial for optimizing Poland's vaccine market access pathway, ensuring timely and efficient population-wide vaccine access.

Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B.

UNLABELLED: Tenofovir disoproxil fumarate (DF) is highly effective for the suppression of hepatitis B virus (HBV) in chronically infected adults. This study evaluated the safety and efficacy of tenofovir DF in adolescents with chronic hepatitis B (CHB). In this double-blind, placebo-controlled trial, adolescents 12 to <18 years of age with CHB were randomized to tenofovir DF 300 mg (n = 52) or placebo (n = 54) once daily for 72 weeks. The primary endpoint was virologic response (HBV DNA <400 copies/mL) at week 72. One hundred six patients were enrolled; 101 patients completed 72 weeks of treatment. At baseline, 91% of patients were hepatitis B e antigen-positive and 85% had prior exposure to HBV therapy. A virologic response was observed in 89% (46/52) of patients who received tenofovir DF and 0% (0/54) of patients who received placebo (P < 0.001). Treatment response was not affected by prior HBV treatment. Furthermore, no resistance to tenofovir DF developed through week 72. Among patients with an alanine aminotransferase (ALT) level greater than the upper limit of normal at baseline, normalization of ALT occurred in 74% of patients receiving tenofovir DF and 31% of patients receiving placebo (P < 0.001). The rate of grade 3/4 adverse events was higher among patients treated with placebo (24%) than patients treated with tenofovir DF (10%). No patients met the safety endpoint of a 6% decrease in spine bone mineral density at week 72. CONCLUSION: Tenofovir DF therapy in HBV-infected adolescents was well tolerated and highly effective at suppressing HBV DNA and normalizing ALT values in both treatment-naïve adolescents and those with prior exposure to HBV therapy.