Although programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) blockade has transformed treatment in several malignancies, its role in prostate cancer remains uncertain. Interest in combination therapy, tumor-microenvironment modulation, and biomarker-guided selection highlights the need to clarify research trends. To characterize the knowledge structure, hotspots, thematic evolution, and clinical-trial evidence on PD-1/PD-L1 in prostate cancer. Publications were retrieved from the Web of Science Core Collection and Scopus. CiteSpace, VOSviewer, R, and Python were used to analyze publication trends, collaboration networks, thematic evolution, and knowledge flow. Clinical-trial reports identified in PubMed were screened and summarized. A total of 2,641 publications were included, comprising 1,421 original articles and 1,220 reviews, involving 17,180 authors and 4,658 keywords. Annual publications increased after 2014 and reached a peak in 2022. Among the candidate models, the logistic model performed best (AIC = 116.4), with the fitted trajectory suggesting a possible slowing. The United States and China were the leading contributors, whereas Canada, Germany, and the United Kingdom showed higher proportions of multinational collaboration. Research increasingly emphasized mechanism-driven and precision-oriented strategies, while exploratory and pan-cancer studies remain part of its knowledge base. The 13 included clinical trials covered diverse combination, but evidence was heterogeneous and no standardized treatment paradigm has yet been established. This multidatabase delineates the knowledge structure, evolution, and emerging directions of PD-1/PD-L1 research in prostate cancer. Current evidence indicates limited activity in unselected populations, whereas potential benefit may be concentrated in biomarker-defined subgroups and selected combinations requiring prospective validation.
In the United States (US), the highest incidence of invasive meningococcal disease (IMD) is among infants aged ≤ 1 year (y). While most IMD cases in US infants are caused by meningococcal serogroup B (MenB), there is no MenB vaccine approved or recommended for US children < 10 y. This study sought to understand general attitudes toward vaccination, knowledge of IMD, and MenB vaccine preferences among parents/caregivers of children ≤ 18 months. An online survey was conducted in November-December 2024 among US parents/caregivers of children ≤ 18 months. Survey responses were analyzed descriptively. Overall, 1,051 parents/caregivers participated in the study. Most parents'/caregivers' children had received all age-appropriate immunizations (73.4%). Of the 266 respondents (25.3%) whose children had received some or no immunizations, 59.8% reported concerns regarding potential vaccine side effects. Most parents/caregivers were familiar with IMD, but knowledge gaps exist regarding its risk and presentation in infants. Two-thirds of parents/caregivers (66.3%) would accept a MenB vaccine for their child if it were included in the Centers for Disease Control and Prevention immunization schedule as optional and recommended by a healthcare provider (HCP); acceptance increased to 72.1% following receipt of IMD information. Perceived barriers to uptake of a potential MenB vaccine focused on HCP-driven communication and guidance. Most US parents/caregivers understood the importance of vaccination and indicated acceptance of a potential MenB vaccine for their child ≤ 18 months. This study highlights the critical role of HCPs in addressing concerns and knowledge gaps to promote IMD prevention in US children ≤ 18 months.
The epidemiological impact of lowering the vaccination age of German adults from 60 to 50 y was evaluated. An age- and serotype-specific dynamic transmission model was used to evaluate the impact of vaccination with either the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or the 20-valent or 21-valent pneumococcal conjugate vaccines (PCV20 and V116, respectively) on pneumococcal disease incidence, including invasive pneumococcal disease (IPD) and inpatient and outpatient non-bacteremic pneumococcal pneumonia, over 10 y. The base case (PPSV23 of ages ≥60 at a 30% vaccination coverage rate [VCR]) was compared against four alternative scenarios with varying pneumococcal conjugate vaccines (PCV20 vs. V116) and starting age of universal vaccination (60 vs. 50) at the same VCR of 30%. Among all adults (ages ≥18) and compared to PPSV23 vaccination at ≥60 and a VCR of 30%, V116 led to 415,452 fewer cases of total pneumococcal disease, while vaccination at ≥50 led to 520,128 fewer cases; PCV20 with those same settings led to 230,950 and 325,694 fewer cases, respectively. When vaccinating ages ≥60 and ≥50 with V116, the projected incidence of IPD in year 10 declined to 22.1 and 20.5 per 100,000, respectively, and when using PCV20 in the same conditions, incidence was 23.0 and 21.8, respectively. In summary, lowering the adult vaccination age enhanced the epidemiological impact of pneumococcal vaccination in Germany, with V116 showing the greatest overall reductions in disease.
Herpes zoster (HZ) poses a substantial health burden among older adults, yet HZ vaccination coverage remains low in mainland China. This study examined the associations between HZ vaccination uptake and factors at both individual and interpersonal levels. This was a cross-sectional survey conducted in Shenzhen, China, between August and October 2024. A total of 1,556 Shenzhen residents aged ≥60 y with established administrative health records were recruited through multistage random sampling. Multivariable multilevel logistic regression models were fitted (level 1: individual participants; level 2: community health centers). Among the participants, 8.0% received a HZ vaccination. After adjusting for background characteristics that were significantly associated with HZ vaccination uptake in the literature and this study, better understanding (coherence) (AOR: 1.15, 95%CI: 1.07, 1.24) was associated with higher HZ vaccination uptake. Being tired of receiving repeated vaccination (vaccination fatigue) (AOR: 0.79, 95%CI: 0.62, 0.99) was correlated with lower HZ vaccination uptake. There is a strong need to improve HZ vaccination coverage among older adults in China. These findings identified potentially modifiable psychosocial factors that warrant evaluation in prospective or intervention studies.
Radial nerve injury following intramuscular injection into the upper arm is rare but clinically significant. Although injection-site selection is important, the effect of shoulder position, particularly internal rotation, on radial nerve location remains unclear. Because the radial nerve courses within the triceps brachii and pierces the lateral intermuscular septum close to the humerus, we hypothesized that shoulder abduction combined with internal rotation would decrease the distance from the acromion to the radial nerve relative to the neutral arm-at-side position. In this cadaveric anatomical study, six fresh-frozen upper limbs (n = 6) were examined in four shoulder positions combining 0° or 80° of internal rotation with 0° or 40° of abduction. The high-risk zone was defined as the region where the radial nerve coursed relatively close to the skin surface while running along the surface of the humerus. The proximal border of this zone was located 18.5 ± 1.5 cm below the acromion in the neutral arm-at-side position and shifted proximally to 13.5 ± 1.4 cm with combined abduction and internal rotation. Shoulder position significantly affected the distance from the acromion to the proximal border of the high-risk zone (p < .001). This proximal shift narrowed the anatomical safety margin between the acromion and the radial nerve. It may therefore increase the risk of radial nerve injury during deltoid intramuscular injection in the hand-on-ipsilateral-hip posture.
Influenza poses a significant public health risk, particularly for pregnant women due to physiological and immunological changes. Despite strong recommendations and proven safety of influenza vaccination, uptake remains suboptimal. This study aimed to identify predictors of influenza vaccination among Iranian pregnant women using an integrated Health Belief Model (HBM) and Theory of Planned Behavior (TPB). A cross-sectional analytical study was conducted among 630 pregnant women attending urban and rural health centers and private clinics in Fasa and Shiraz, Iran. Participants were selected using multistage stratified sampling. Data were collected by a validated, researcher-developed questionnaire based on HBM and TPB constructs. Statistical analyses included descriptive statistics, Spearman correlation, logistic regression, and Structural Equation Modeling (SEM). The mean age of participants was 29.36y, and 73% received the influenza vaccine during the current pregnancy. The most common barriers were concerns about side effects (49.4%), limited access (28.2%), lack of provider recommendation (27.1%), and insufficient information (34.1%). SEM results indicated that perceived susceptibility (beta = 0.18), perceived barriers (beta = -0.15), and attitude (beta = 0.13) were significant predictors of behavioral intention. Behavioral intention had a small but significant effect on actual vaccination (beta = 0.08). Subjective norms, self-efficacy, and perceived behavioral control were not significant predictors. Perceived susceptibility, common barriers, and attitude play key roles in shaping vaccination intention, while structural factors limit the translation of intention into action. Interventions focusing on education, improving provider-patient communication, and reducing access barriers may enhance vaccination uptake among pregnant women.
Human papillomavirus (HPV) vaccination is an effective strategy for preventing cervical cancer, yet vaccine uptake in Malawi remains low because of misinformation, limited awareness, and parental hesitancy. This study describes the implementation of a youth-led school and community engagement initiative to promote HPV vaccine awareness in Lilongwe, Malawi, and highlights lessons for future immunization programs. We conducted a descriptive implementation case study of a two-day youth-led engagement initiative coordinated by fellows of the 2025-2026 Global Health Corps Malawi Leadership Accelerator in collaboration with the Lilongwe District Health Office, Kawale Primary School, and partner organizations. Activities included stakeholder meetings, school health education, myth-busting sessions, learner-centered activities, community dialogs, distribution of educational materials, and on-site HPV vaccination services. Girls aged 9-14y were the primary vaccination beneficiaries, while parents, caregivers, teachers, religious leaders, and community stakeholders were engaged to strengthen vaccine acceptance. Implementation data were collected through attendance records, field notes, dialogue summaries, and reflections. Descriptive statistics and qualitative content analysis were used. The initiative reached over 500 adolescent girls through school awareness activities and engaged 45 community stakeholders across six sites. Two community dialogue sessions were conducted, 1,000 educational materials distributed, and 100 eligible girls received HPV vaccination. Community discussions identified concerns about fertility, vaccine safety, and gender targeting, while trust in health workers, school involvement, participatory dialogue, and community leader support facilitated engagement. Youth-led, community-centered engagement highlighted lessons for improving HPV vaccination through addressing misinformation, building trust, and strengthening health system readiness.
Dupilumab is effective for the treatment of moderate‑to‑severe type 2 inflammatory diseases; however, its real‑world safety profile in pediatric patients remains to be further clarified. This retrospective pharmacovigilance study analyzed U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) data from 2017 to 2025, including 44,593 reports where dupilumab was the primary suspect drug in children. Disproportionality analyses (ROR, PRR, BCPNN, MGPS), time-to-onset analysis, stratified analysis, and Weibull modeling assessed adverse event (AE) distribution and patterns. Results showed balanced sex distribution (male 50.1%, female 48.6%), with adolescents (12-17y) most common (45.3%), and report counts increasing over time. 93 positive safety signals were detected. The most common core AEs were rash (4,105 cases; ROR = 4.55, 95% CI: 4.38-4.72), injection site pain (3,582 cases; ROR = 8.59, 95% CI: 8.22-8.97), and skin exfoliation (1,834 cases; ROR = 3.41, 95% CI: 3.23-3.59). Potential unlisted signals included vitiligo (33 cases; ROR = 10.46, 95% CI: 6.52-16.78), skin depigmentation (32 cases; ROR = 13.04, 95% CI: 7.85-21.66), and eye color change (13 cases; ROR = 7.06, 95% CI: 3.54-14.11). Stratified analyses indicated distinct patterns of adverse‑event reporting across age and sex strata. Among cases with complete temporal information, most AEs occurred within 30d after dupilumab initiation, with a median time‑to‑onset of 14d. In conclusion, this large-scale spontaneous-reporting study detected potential safety signals in children. Given FAERS data limitations, the associations should be viewed as hypothesis-generating rather than confirmatory, and may inform future signal validation and prospective studies.
Although vaccines remain a mainstay tool for the prevention of infectious diseases, their efficacy, safety, and trust among the population remain controversial. For an effective rollout of the HPV vaccine in Pakistan, financial constraints, health system fragility, and complex cultural values should be kept in mind, and these should be apprehended as both facilitators and barriers, since these findings will help policymakers to design effective interventions and improve public trust. To explore barriers and motivators to HPV vaccine uptake in Pakistan, the study used a descriptive qualitative study design. It was conducted from February 2025 to August 2025 across districts of Northern Punjab and Southern Punjab. Inclusion of diverse stakeholders such as community workers/religious scholars, healthcare providers, teachers/school administrators, adolescent girls, and their parents/guardians allowed us a better understanding of multilevel influencers on HPV vaccine acceptance. Barriers to HPV vaccination were summarized under BeSD framework, including fear of side effects, vaccine skepticism, misinformation via social media, religious perception, restricted social and peer norms, fear-based motivation, long waiting time, service dissatisfaction, patriarchal decision-making, and community resistance. Conversely, facilitators included recognition of vaccine need and benefits, supportive family and community norms, health worker counseling, public health advocacy, trust in school authorities, religious belief, self-determination, effective outreach and door-to-door services, and gender-neutral vaccine acceptance. The findings underscore the need for culturally sensitive, trust-building strategies that go beyond a clinical approach to effectively strengthen equitable HPV vaccine uptake, improved vaccine confidence, and ultimately reduced HPV-related diseases.
Adjuvants can enhance the elicited immune responses to recombinant hemagglutinin (HA) proteins following intramuscular vaccination. In this study, computationally optimized broadly reactive antigen (COBRA) designed HA proteins were adjuvanted with the W805EC oil-in-water nanoemulsion ("NE01") and used to vaccinate mice. The elicited influenza-specific humoral and cellular immune responses were evaluated. Mice vaccinated with adjuvanted COBRA H1 and H3 HA vaccine candidates had higher antibody titers compared to mice vaccinated with unadjuvanted HA proteins. Mice administered COBRA HA plus NE01 had higher hemagglutination inhibition (HAI) specific antibody titers against a panel of H1N1 and H3N2 influenza viruses, as well as higher levels of interferon-gamma (IFN-γ) secreting splenocytes. Mice vaccinated with adjuvanted COBRA HA proteins had statistically less weight loss following challenge, as well as undetectable viral lung titers compared to mice administered unadjuvanted vaccine.
Infant RSV prevention is undergoing a public-health paradigm shift toward scalable, broad-eligibility passive immunization. This review examines nirsevimab (Beyfortus®), a long-acting recombinant IgG1κ monoclonal antibody targeting the conserved site Ø of prefusion RSV F protein. Its extended half-life enables season-long protection with a single dose, overcoming key limitations of palivizumab. A validated manufacturing platform and stringent release specifications ensure consistent quality and potency. Pivotal trials demonstrated high efficacy against RSV-associated lower respiratory tract infection hospitalization (RSVH), while the pragmatic HARMONIE trial confirmed an 83.2% reduction in RSVH under routine conditions. Postlicensure studies across multiple countries report 70-90% effectiveness against RSVH and substantial reductions in intensive care admissions. Comparative 2024-2025 data further suggest greater protection than maternal RSVpreF vaccination. Nirsevimab represents a scalable public-health intervention that can be used alone or complement maternal RSV vaccination, warranting continued surveillance of effectiveness, safety, and viral escape.
Human papillomavirus (HPV) vaccination is a key preventive measure against cervical cancer. In Japan, proactive recommendations for HPV vaccination were suspended from 2013 to 2022, resulting in persistently low coverage. We explored the post-intervention knowledge, attitudes, and short -term self-reported HPV vaccination behavior following a near-peer educational intervention by medical students. Between February 2022 and March 2024, medical students conducted 1-hour sessions covering HPV transmission, cervical cancer prevention, and vaccine efficacy. The sessions incorporated quizzes, discussions, and workshops in which high school students created role-play scenarios or social media messages to promote HPV vaccination. A follow-up survey was administered 1-2 weeks after the sessions to assess vaccination uptake, knowledge, and self-reported explanatory ability. Of 864 junior and senior high school students who participated in the sessions, 332 were included in the followed-up analysis. Of these, 248 were unvaccinated before the session: 134 females and 114 males. Within two weeks, 10 female (7.5%) and one male (0.9%) reported receiving HPV vaccination. Students with positive vaccination intentions demonstrated higher comprehension scores than those without such intentions. Voluntary participants had higher knowledge scores than whole-class attendees. Subjective and objective comprehension scores were positively correlated, although there were some discrepancies. Vaccinated respondents were more likely than unvaccinated respondents to correctly identify HPV-preventable cancers. Near-peer outreach sessions delivered by medical students may represent a useful approach to enhancing adolescents' understanding of HPV vaccination. Leveraging the near-peer position of medical students may be a promising approach to address vaccine hesitancy in Japan.
Human papillomavirus (HPV) is a major global public health concern, causing genital warts and cancers of the cervix, anus, oropharynx, vulva, and penis. People living with HIV (PLWH) face a disproportionately elevated burden of HPV infection and HPV-related malignancies due to chronic immunosuppression. We conducted a systematic review and meta-analysis searching six databases from January 2006 to June 2026 without language restrictions. Twenty-five studies were included in the systematic review; 12 independent studies (N = 1,493 for HPV16) were included in the quantitative meta-analysis. Using a DerSimonian-Laird random-effects model with logit transformation, pooled seroconversion rates were: HPV16 97.8% (95% CI: 94.9-99.1%; I2 = 89.6%; 15 datasets), HPV18 94.2% (95% CI: 86.1-97.7%; I2 = 95.8%; 13 datasets), HPV6 97.0% (95% CI: 93.7-98.6%; I2 = 66.1%; 10 studies), and HPV11 97.1% (95% CI: 90.5-99.1%; I2 = 95.5%; 10 studies). CD4 count was the most consistently reported modifier of immunogenic response: HPV16 seroconversion was 98.5% in PLWH with CD4 > 350 cells/μL vs. 71.1% in those with CD4 ≤ 200 cells/μL (ACTG A5240). All three vaccine generations demonstrated high immunogenicity. Two doses of the nonavalent vaccine were non-inferior to three doses in virologically suppressed women (Papillon RCT). No vaccine-related serious adverse events were reported. GRADE certainty of evidence was moderate for HPV16, HPV6, and HPV11, and low for HPV18. Prophylactic HPV vaccination achieves high seroconversion rates across all vaccine generations in PLWH. CD4 count significantly modifies vaccine response, underscoring the importance of vaccination before severe immunosuppression develops. These findings support current international recommendations advocating HPV vaccination for all PLWH.
This study aimed to determine the prevalence and correlates of adequate tetanus toxoid (TT) immunization among married women in Afghanistan. This cross-sectional study analyzed data from the 2022-2023 Afghanistan Multiple Indicator Cluster Survey (MICS), focusing on 12,450 married women aged 15-49y who had a live birth in the two years preceding the survey. Multivariable logistic regression determined the correlates of adequate TT immunization. The prevalence of adequate TT immunization was 49.9% (95% CI 48.2%-51.6%). The odds of adequate TT immunization were higher in women with primary (AOR 1.32) and secondary/higher (AOR 1.57) education, in women who used 1-3 (AOR 3.06) and ≥4 (AOR 4.67) antenatal care (ANC) visits, those living in Central High region (AOR 4.20), those with access to media (AOR 1.29), and in women belonging to second (AOR 1.33), third (AOR 1.25) and fourth (AOR 1.26) household wealth quintiles. On the other hand, the likelihood of adequate TT immunization was lower in women aged 40-49y (AOR 0.76) and those living in the East (AOR 0.76) and West (AOR 0.68) regions of Afghanistan. Only half of married women in Afghanistan had adequate TT immunization, highlighting substantial gaps in coverage. Strengthening health education, improving equitable access to immunization services, and enhancing communication through mass media; particularly targeting older, less-educated, and economically disadvantaged women, are essential to improve TT coverage and progress toward maternal and neonatal tetanus elimination in Afghanistan.
Varicella remains a common childhood infection worldwide. Understanding long-term trends and identifying key determinants of disease burden are essential for informing vaccination strategies and public health planning. Data were obtained from the Global Burden of Disease (GBD) 2021 study and the global varicella vaccination policy information. Extreme Gradient Boosting (XGBoost) model was trained to predict the disease burden for 2030. This model estimated the incidence, prevalence, and disability-adjusted life years (DALYs) for varicella among children aged 5-9 y worldwide. Shapley Additive exPlanations (SHAP) was employed to identify key factors and inform public health strategies. From 1990 to 2021, the rate of global incidence rose from 1,028.46/100,000 to 1,048.24/100,000, prevalence from 30.81/100,000 to 31.07/100,000, and DALYs declined from 21.09/100,000 to 12.36/100,000. By 2030, these metrics are projected to fall to 897.01/100,000, 28.96/100,000, and 11.71/100,000, respectively. From 1990 through 2030, Southeast and South Asia had the highest varicella incidence, Asian and Pacific Island nations had the highest prevalence, and sub-Saharan Africa and South Asia had the highest DALYs. SHAP identified population as the strongest predictor (mean absolute SHAP value: 0.167 for incidence and 0.103 for prevalence), and higher vaccination program tier may be associated with lower DALYs. Varicella burden among children aged 5-9 y has declined globally, but model projections indicate that regional disparities will persist. The lack of vaccination coverage and cohort-level immunization data limits interpretation of vaccine effects; future studies should incorporate both coverage and cohort exposure information to strengthen policy evaluation.
Cervical cancer is a preventable threat to women's health, and human papillomavirus (HPV) vaccination is key primary prevention. Caregiver hesitancy may affect vaccination of age-eligible girls.We examined caregivers' willingness to vaccinate primary and secondary school girls against HPV and factors in six ethnic autonomous prefectures of Qinghai Province. From December 2024 to February 2025, we conducted a cross-sectional survey of caregivers of girls in selected classes at 12 schools, using multistage cluster convenience sampling. The questionnaire included Health Belief Model (HBM), Theory of Planned Behavior (TPB), and Perceived Social Support Scale (PSSS) items. Factors were assessed with univariable and four-step hierarchical multiple linear regression, sequentially entering sociodemographic, HBM, TPB, and PSSS blocks. Willingness correlated with perceived susceptibility and severity, cues to action, attitudes, perceived behavioral control, and subjective norms. In univariable analyses, all HBM, TPB, and social-support dimensions except perceived barriers were positively associated with willingness. Hui caregivers had lower willingness, while higher education, middle income, and party/government-agency or public-institution employment predicted higher willingness. In hierarchical multiple regression, Hui ethnicity vs. Han ethnicity predicted lower willingness (B = -0.229, P = .003). Cues to action (β = 0.121, P = .024), perceived barriers (β = 0.128, P < .001), attitudes (β = 0.203, P < .001), perceived behavioral control (β = 0.107, P = .001), and subjective norms (β = 0.323, P < .001) were positively associated. HPV vaccination promotion should be tailored to Qinghai's ethnic autonomous prefectures, with authoritative school and primary-care recommendations, clear vaccine information, and vaccination-process support, while identifying barriers. Future qualitative and prospective implementation studies should clarify decision-making mechanisms and assess intervention acceptability and effects on vaccine uptake in resource-limited settings.
This scoping review consolidates survey research conducted among university students across the League of Arab States to understand the nature and extent of COVID-19 vaccine hesitancy and acceptance. Using PRISMA-ScR guidelines, a search was conducted across 10 databases covering publications from 2020 to 2024. Fifty-three studies met the inclusion criteria. Reported determinants of vaccine acceptance and hesitancy aligned with key constructs of the Health Belief Model, including perceived susceptibility, perceived severity, perceived benefits, and perceived barriers. Concerns regarding vaccine safety, effectiveness, and side effects were among the most frequently reported reasons for hesitancy, while perceived protection of self and others, trust in health authorities, and institutional requirements were associated with vaccine acceptance. Findings suggest that vaccine decision-making among university students was influenced by an interaction of individual, familial, social, and informational factors. These results help inform future vaccination communication, education, and public health strategies in university settings across the region.
The gut microbiota-tryptophan (TRP) metabolism-immune axis is one of the core pathogenic mechanisms in inflammatory bowel disease (IBD). Physiologically, gut microbes convert dietary TRP into bioactive metabolites that regulate intestinal immune balance and barrier function via AHR. In IBD, this axis enters a vicious cycle of dysbiosis, metabolic disruption, and immune imbalance - characterized by reduced beneficial bacteria, excessive 5‑HT production, and kynurenine pathway overactivation - which drives T‑cell dysregulation, aberrant macrophage polarization, and compromised barrier integrity. Therapeutic strategies are shifting from single‑target to integrated approaches, combining probiotics, engineered bacteria, AHR agonists, IDO1 inhibitors, immunomodulators, and ROS‑responsive nanomedicines. By achieving multi‑node synergistic remodeling, this review provides a theoretical foundation for systemic strategies that coordinate microbial regulation, metabolic intervention, and immune targeting, thereby offering new avenues for the effective treatment of IBD.
Adverse reactions are closely associated with vaccination sites, making site selection vital for clinical administration of the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine. This retrospective observational study enrolled 636,169 DTaP inoculations in Wuxi from 2020 to 2024. Adverse reaction data were extracted from the National Adverse Events Following Immunization Surveillance System of China, and dose data were obtained from the Jiangsu Province Vaccination Integrated Service Management Information System. We compared adverse reaction reporting rates stratified by overall incidence, severity, vaccine dose, and clinical manifestations, as well as constituent proportions of adverse reactions according to onset time between upper arm and buttock injection groups. The upper arm group had slightly higher reporting rates of adverse reactions and common reactions than the buttock group, at 23.88 (95% CI: 22.54-25.22) vs. 17.89 (95% CI: 15.56-20.21) and 23.13 (95% CI: 21.81-24.45) vs. 16.94 (95% CI: 14.68-19.20) per 10,000 doses, both p < .001, while rare reaction rates were comparable, at 0.75 (95% CI: 0.51-0.98) vs. 0.95 (95% CI: 0.41-1.48) per 10,000 doses, p = .473. Slightly elevated adverse reaction rates were also found in upper arm administration for the first and second doses. Redness and swelling, induration, and fever were the predominant adverse symptoms, all showing modestly elevated rates after upper arm injection. The adverse reactions at both sites were predominantly common reactions within expected range. Despite a slightly elevated risk of common reactions, upper arm injection may be the preferred site for DTaP vaccination for overall safety.
Recent articles claim that randomized clinical trials (RCTs) have not documented non-specific effects of vaccines (NSE), i.e. broader immunomodulatory effects of vaccines. We reviewed the role of RCTs in the discovery of NSEs. The articles claiming no NSEs misread the literature, disregarded non-RCT data, and did not take interactions with other interventions into consideration. RCTs have played a limited role in the discovery of the NSEs of vaccines. Instead, contradictions in non-RCT data have helped to document NSEs; most important have been abrupt mortality changes, sex-differential effects, differential effects by sequence of vaccinations, maternal priming effects, beneficial boosting, negative boosting, mortality effects after disease eradication/elimination, and interacting interventions changing the mortality ratio (MR) in RCTs. Vaccine efficacy studies assume that true protective effects are independent of context; in contrast, the immunological mechanisms underlying NSEs are context-dependent as other vaccines, micronutrients and immune history may affect the capacity of the immune system to protect against unrelated infections. Thus, NSEs do exist. The way forward will be to intensify studies of the contextual factors affecting the NSEs to optimize their usefulness for vaccine programmes.
