Global Vaccines (United States)

To better understand parents/caregivers' perceptions of adverse events (AEs) associated with the whole-cell pertussis vaccine and the impact of family routine activities. This cross-sectional study was conducted in the city of São Paulo, Brazil, using a parent-reported outcomes approach to describe the perception of AEs following immunization with the whole-cell pertussis vaccine. A total of 1260 parents/caregivers of children who received a whole-cell pentavalent vaccine were enrolled in the study. The most frequently reported AE was tenderness/pain at the injection site (72.4%). Parents/caregivers also reported at least some grade (a little bit more, moderate, or significant/severe) of redness at the injection site (25.2%), swelling (32.4%), a fever ≥38°C (41.9%), vomiting (7%), and changes in appetite (27.1%), sleeping (34%), and crying (43.7%) patterns. Overall, 86.8% of the parents/caregivers reported at least one AE or change in the child's behavior. A significant positive gradient was observed, i.e., the higher the income, the higher the frequency of AEs/behavior change perceived by the parents/caregivers. The analysis by dose did not show significant differences, except for local pain/tenderness (77.6% vs. 73.5% for D1 and 65.4% for D3, p=0.001) and changes in child's appetite (34.3% vs. 22.9% for D1 and 26% for D3, p=0.001) that were more frequent among children receiving the first booster, while changes in child's sleeping (39.1% vs. 26% for D3 and 34.3% for the first booster, p<0.001) and crying (49% vs. 37.7% for D3 and 42.2% for the first booster, p=0.003) patterns were more frequent among those receiving D1. Our study showed that the reported AEs following wP-pentavalent vaccine significantly impact Brazilian children and their families. The switch to less reactogenic vaccines, such as aP hexavalent vaccine, can diminish this impact and contribute to recovering high VCR rates, avoiding outbreaks of vaccine-preventable diseases (VPDs).

Laboratory confirmation of invasive meningococcal disease (IMD) relies on detection of Neisseria meningitidis in a biological specimen. Clinical management guidelines for patients presenting with signs and/or symptoms of meningitis and encephalitis emphasize the need for appropriate specimen collection for laboratory testing. To explore the potential for IMD under-diagnosis, we reviewed medical records of patients admitted with signs and/or symptoms of meningitis or encephalitis at five hospitals in Louisville, Kentucky, in 2014 to 2023. Among 675 patients admitted with meningitis and/or encephalitis with cerebrospinal fluid (CSF) cultures who received antibiotics, 300 (44.4%) received antibiotics before CSF collection. Among 431 with blood cultures who received antibiotics, 133 (30.9%) received antibiotics before blood collection. Among 751 patients with CSF collected, 651 (86.7%) CSF specimens were tested using polymerase chain reaction (PCR) for N. meningitidis detection. No blood specimens were PCR-tested. These findings indicated that current standard-of-care practices may lead to IMD under-diagnosis. Since public health surveillance relies on IMD laboratory diagnosis, these findings highlight the potential for under-ascertained IMD by surveillance.

Shigellosis is a global public health challenge that mostly affects low- and middle-income countries and causes considerable morbidity and mortality among children under 5 y of age. Multi- and extensively drug-resistant Shigella sonnei strains associated with recent outbreaks in high-income countries exacerbate the problem and have prompted the World Health Organization to include Shigella spp. among the high-risk pathogens for which novel prophylactic and therapeutic tools are urgently needed. Among the most promising and cutting-edge solutions, monoclonal antibodies are gaining considerable attention in the infectious diseases field. Here, we report the discovery of human monoclonal antibodies against S. sonnei, a species whose prevalence is constantly increasing worldwide and is associated with frequent drug-resistant infections. We isolated antibodies generated in response to an experimental S. sonnei vaccine followed by a controlled human infection and screened them by using a panel of high-throughput assays. We identified a molecule which exhibited potent bactericidal activity in vitro, inhibition of invasion of epithelial cells and conferred full protection from S. sonnei infection in vivo. Overall, our study provides a candidate antibody that can rapidly progress to industrial development for application as a prophylactic, therapeutic, and diagnostic tool against shigellosis.

Identifying the circumstances of transmission of an emerging infectious disease rapidly is central for mitigation efforts. Here, we explore how large language models (LLMs) can automatically extract such circumstances from free-text descriptions in online surveys, in the context of Covid-19. In a nationwide study conducted online in France, we enrolled 545,958 adults with recent SARS-CoV-2 infection and inquired about the circumstances of transmission in both closed-ended and open-ended questions. First, we trained a classification model based on a pretrained LLM to predict one of seven predefined infection contexts (Work, Family, Friends, Sports, Cultural, Religious, Other) from the free text in answers to open-ended questions. We achieved an unbalanced accuracy of 75%, which increased to 91% when eliminating the 43% highest entropy responses. Second, we used topic modeling to define clusters of transmission circumstances agnostically. This led to 23 clusters, which agreed with the seven predefined infection contexts, but also provided finer details on previously undefined circumstances of transmission. Our study suggests that LLM-based analysis of free text may alleviate the need for closed-ended questions in epidemiological surveys and enable insights into previously unsuspected circumstances of transmission. This approach is poised to accelerate and enrich the acquisition of epidemiological insights in future pandemics.

Most bacterial small regulatory RNAs (sRNAs) modulate gene expression by forming complementary base pairs with target mRNAs, dependent upon the RNA chaperone Hfq. Hfq has three RNA-binding faces (proximal, rim, and distal), facilitating simultaneous binding of sRNAs and target mRNAs. Here, we systematically examined the functional impact of point mutations in the RNA binding faces on in vivo pairing, using the RNA Interaction by Ligation and Sequencing (RIL-seq) approach. The distal and proximal Hfq binding face mutants retained substantial numbers of RNA–RNA interactions (significant chimera counts or S-chimeras). However, the rim face mutant R16A showed a near-complete loss of S-chimeras, although Hfq R16A retained partial RNA binding activity as well as partial regulatory activity. Intracellular RIL-seq (iRIL-seq), a method with fewer in vitro processing steps, led to more S-chimeras in R16A but there were still fewer than for wild type Hfq and somewhat different sets of prevalent RNA-RNA pairs. Our analysis provides insights into how the RNA-binding faces of Hfq contribute to pairing in vivo, document the key role for the rim face in stabilizing RNA pairs on Hfq, and highlight intriguing differences captured by different RNA-RNA interactome approaches.

This study aimed to explore willingness to use and preference for long-acting injectable PrEP (LAI-PrEP) among Thai youth at risk of HIV. A cross-sectional study was conducted in 100 Thai youth aged 18 to 24 years attending a sexual health clinic in Bangkok, Thailand. Participants received information about oral and LAI-PrEP before completing a questionnaire. Of the 98 participants willing to use pre-exposure prophylaxis, 47 preferred the injectable form. Preference for the injectable form was higher among individuals not currently using oral pre-exposure prophylaxis, affordability and longer injection intervals were key for acceptance of long-acting injectable pre-exposure prophylaxis.

We investigated the steady-state pharmacokinetics of generic abacavir (ABC)/lamivudine (3TC) dispersible tablets (DTs) in young children living with HIV aged 3 months to <7 years, weighing 6 to <20 kg. Twenty-eight Thai children were enrolled and received ABC/3TC-DT plus pediatric dolutegravir-DT once daily. ABC/3TC was administered using WHO weight band (WB) doses: 180/90 mg, 240/120 mg and 300/150 mg for children weighing 6 to <10 kg (WB 1, n = 7), 10 to <14 kg (WB2, n = 9) and 14 to <20 kg (WB3, n = 12), respectively. ABC geometric mean (GM) AUC 0-24 h (CV%) was 14.2 (50.5%), 15.6 (32.6%) and 20.7 (28.3%) mg.h/L, respectively, and 3TC GM AUC 0-24 h was 14.8 (44.1%), 18.2 (28.0%) and 19.9 (26.2%) mg.h/L, respectively. ABC and 3TC exposures were within target ranges across WBs. These data supported current ABC/3TC-DT WHO-weight band dosing guidance for young children in Thailand.