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EBioMedicine Jun 2024Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing...
BACKGROUND
Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children.
METHODS
We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining.
FINDINGS
After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens.
INTERPRETATION
Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19.
FUNDING
This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).
PubMed: 38896919
DOI: 10.1016/j.ebiom.2024.105203 -
Health Science Reports Jun 2024Food-borne illness is a public health concern in developing countries because of improper food handling and sanitation practices, irregular medical checkups, lack of...
BACKGROUND AND AIMS
Food-borne illness is a public health concern in developing countries because of improper food handling and sanitation practices, irregular medical checkups, lack of clean water supplies, and inadequate education among food handlers. This study investigated the burden of bacterial food-borne illness, antibiotic resistance patterns, and associated factors among food handlers in prison and nonprison food establishment settings.
METHODS
A cross-sectional study was conducted from August 2022 to January 2023 among asymptomatic food handlers in Shewa Robit town. A total of 384 food handlers participated. Data were collected using structured questionnaires. Stool and hand swab samples were collected and cultivated onto MacConkey agar, xylose-lysine-deoxycholate, Mannitol salt agar, and blood agar, and incubated at 37°C. Bacterial species were identified using biochemical tests and gram staining. Mueller-Hinton agar was used in Kirby Bauer's disk diffusion method. Data were entered and analyzed using SPSS. Descriptive and logistic regression analysis were performed.
RESULTS
Fecal and hand carriage rate of bacterial isolates were 106 (27.6%), and 214 (55.7%), respectively. Out of the 102 bacterial isolates, the most common ones from stool samples were 71 (18.5%), 12 (3.1%), and spp. 7 (1.8%). Among 214 bacterial isolates, coagulase-negative 115 (29.9%) and 66 (17.3%) were identified from hand swab samples. Hand washing practice after restroom with water (adjusted odds ratio [AOR] = 2; 95% confidence interval [CI]: 1.16-3.45), irregular medical checkups (AOR = 2.49; 95% CI: 1.35-4.59), and did not receive food safety and hygiene training (AOR = 2.33; 95% CI: 1.34-4.05) were statistically significant association with food-borne illness.
CONCLUSIONS
Foodborne pathogens pose a serious health risk in the study areas. The level of antimicrobial resistance are also concerning. Food handlers should therefore get strict regular health education, medical checkups, and training programs to prevent the spread of infections to the customers.
PubMed: 38895551
DOI: 10.1002/hsr2.2199 -
Influenza and Other Respiratory Viruses Jun 2024This phase 2b/3, randomized, placebo-controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This phase 2b/3, randomized, placebo-controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with mild symptoms of coronavirus disease 2019 (COVID-19).
METHODS
The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6-August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125-mg, ensitrelvir 250-mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self-rated the severity of 14 typical COVID-19 symptoms and recorded the data in an electronic diary.
RESULTS
In total, 572 participants (194, 189, and 189 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were included in the intention-to-treat population. Ensitrelvir 125-mg group observed a 77% reduction in the risk of developing any of the 14 COVID-19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment-related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high-density lipoprotein.
CONCLUSIONS
Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID-19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated.
TRIAL REGISTRATION
Japan Registry of Clinical Trials identifier: jRCT2031210350.
Topics: Humans; Male; Female; Adult; Middle Aged; SARS-CoV-2; COVID-19 Drug Treatment; COVID-19; Antiviral Agents; Treatment Outcome; Asymptomatic Infections; Vietnam; Japan; Aged; Republic of Korea; Young Adult; Indazoles; Triazines; Triazoles
PubMed: 38890511
DOI: 10.1111/irv.13338 -
PloS One 2024Diarrheal diseases are important causes of morbidity and mortality, worldwide. The occurrence of multiple pathogens in stool samples of symptomatic and asymptomatic...
Diarrheal diseases are important causes of morbidity and mortality, worldwide. The occurrence of multiple pathogens in stool samples of symptomatic and asymptomatic individuals in resource-limited countries have been repeatedly described. In this study, we assessed the differentiated effects of combined pathogen detections on recorded symptoms. A case-control study was conducted among 620 under-five-year-old children in rural northeastern Tanzania with emphasis of multiple detection. The median age of children was 11 months (IQR = 7, 20), and 52.1% were male. Cases (50.2%, n = 157) were less likely than controls (64.5%, n = 198) to have multiple colonization with gastrointestinal tract (GIT) pathogens. The children's age was positively associated with the likelihood of harboring multiple GIT pathogens [OR, 1.02, 95% CI = 1.01, 1.04]. Shigella spp./enteroinvasive Escherichia coli (EIEC) [OR = 2.80, 95% CI 1.62, 4.83] and norovirus [OR = 2.04, 95% CI 1.23, 3.39] were more common in cases and were strongly associated with diarrhea, while enteroaggregative E. coli (EAEC) [OR = 0.23, 95%CI 0.17-0.33] were more common in controls. Diarrheal diseases in under-five children from rural Tanzania are likely to be due to infections with Shigella spp./EIEC, and norovirus with strongly age-dependent associations.
Topics: Humans; Tanzania; Male; Female; Case-Control Studies; Diarrhea; Infant; Child, Preschool; Rural Population; Shigella; Feces; Gastrointestinal Tract; Norovirus; Escherichia coli
PubMed: 38889116
DOI: 10.1371/journal.pone.0305469 -
Cureus May 2024Ascariasis is one of the most common parasitic infections in the world. It is mostly asymptomatic; however, rarely when the worms migrate to the biliary tract, they can...
Ascariasis is one of the most common parasitic infections in the world. It is mostly asymptomatic; however, rarely when the worms migrate to the biliary tract, they can cause biliary ascariasis. It typically presents with pain abdomen, jaundice, and fever. This case report is about a patient who presented with fever, icterus, breathlessness, loose stools, and altered sensorium but had no abdominal pain. The patient was diagnosed with biliary ascariasis using ultrasound and endoscopic retrograde cholangiopancreatography (ERCP). The patient was treated with endoscopic sphincterotomy and albendazole. The patient remained stable after 10 days. The absence of abdominal pain highlights the variability of the presentation of biliary ascariasis.
PubMed: 38887340
DOI: 10.7759/cureus.60537 -
BMC Infectious Diseases Jun 2024Urinary tract infection is one of the most common infections in humans, affecting women in more proportion. The bladder was considered sterile, but it has a urinary...
BACKGROUND
Urinary tract infection is one of the most common infections in humans, affecting women in more proportion. The bladder was considered sterile, but it has a urinary microbiome. Moreover, intracellular bacteria (IB) were observed in uroepithelial cells from children and women with urinary tract infections (UTIs). Here, we evaluated the presence of IB in urine from healthy people and patients with UTI symptoms.
METHODS
Midstream urine was self-collected from 141 donors, 77 females and 64 males; 72 belonged to the asymptomatic group and 69 were symptomatic. IB was characterized by a culture-dependent technique and visualized by confocal microscopy. Urine was also subjected to the classical uroculture and isolated bacteria were identified by MALDI-TOF.
RESULTS
One-hundred and fifteen uroculture were positive. A significant association was observed between the presence of symptoms and IB (P = 0.007). Moreover, a significant association between the presence of IB, symptoms and being female was observed (P = 0.03). From the cases with IB, Escherichia coli was the most frequent microorganism identified (34.7%), followed by Stenotrophomonas maltophilia (14.2%), Staphylococcus spp (14.2%), and Enterococcus faecalis (10.7%). Intracellular E. coli was associated with the symptomatic group (P = 0.02). Most of the intracellular Staphylococcus spp. were recovered from the asymptomatic group (P = 0.006).
CONCLUSIONS
Intracellular bacteria are present in patients with UTI but also in asymptomatic people. Here, we report for the first time, the presence of S. maltophilia, Staphylococcus spp., and Enterobacter cloacae as intracellular bacteria in uroepithelial cells. These findings open new insights into the comprehension of urinary tract infections, urinary microbiome and future therapies. Uroculture as the gold standard could not be enough for an accurate diagnosis in recurrent or complicated cases.
Topics: Humans; Female; Male; Urinary Tract Infections; Adult; Middle Aged; Bacteria; Urothelium; Epithelial Cells; Urine; Young Adult; Aged; Microbiota; Adolescent
PubMed: 38886658
DOI: 10.1186/s12879-024-09489-5 -
BMJ Open Jun 2024In 2016, WHO estimated there were roughly 374 million new infections among adults of the following four curable sexually transmitted infections (STIs): chlamydia...
Standardised protocol for a prospective international multicentre clinical-based evaluation of point-of-care tests for the screening of genital and extragenital chlamydial and gonococcal infections in men who have sex with men and for the screening of genital chlamydial, gonococcal and infections...
INTRODUCTION
In 2016, WHO estimated there were roughly 374 million new infections among adults of the following four curable sexually transmitted infections (STIs): chlamydia (caused by (CT)), gonorrhoea ( (NG)), syphilis () and trichomoniasis ( (TV)). Accurate point-of-care tests (POCTs) for screening of genital and extragenital CT, NG and TV infections are of great value and have been developed during recent decade. Several tests are commercially available and have shown encouraging performance compared with 'gold-standard' reference tests in laboratory-based studies. However, there is limited data on their clinical performance, including at the POC. Key populations, such as men who have sex with men (MSM), are at higher risk of these STIs at genital and extragenital sites and these STIs are often asymptomatic, especially in extragenital sites and in women. We will conduct a clinical-based evaluation to assess the performance characteristics and acceptability to end-users of molecular-based diagnostic technology for POC/near patient use of the Xpert CT/NG (Cepheid, Sunnyvale, California, USA) test for screening of genital, anorectal and pharyngeal CT and NG infections in MSM and the Xpert CT/NG and Xpert TV (Cepheid, Sunnyvale, California, USA) for screening of genital CT, NG and TV among women at risk for these STIs compared with gold-standard reference nucleic acid amplification tests. This master protocol outlines the overall research approach that will be used in seven countries.
METHOD AND ANALYSES
Consecutive MSM and women at risk presenting at the clinical sites in high, and low- and middle-income countries will be enrolled. The POCTs to be evaluated are Xpert CT/NG and Xpert TV. All procedures will be carried out by trained healthcare staff and tests performed in strict accordance with the manufacturer's instructions. The sensitivity, specificity, positive and negative predictive values for each POCT will be calculated. The study is ongoing with recruitment expected to be completed in all countries by mid-2022 to late-2022.
ETHICS AND DISSEMINATION
Prior to enrolment, this core protocol was independently peer-reviewed and approved by the research project review panel (RP2) of the WHO Department of Sexual and Reproductive Health and Research and by the WHO Ethics Review Committee (ERC). The core protocol has been slightly adapted accordingly to individual countries and adaptations approved by both RP2 and ERC, as well as all relevant institutional review boards at each participating site. Results will be disseminated through peer-reviewed journals and presented at relevant national/international conferences.
Topics: Humans; Male; Female; Chlamydia Infections; Gonorrhea; Point-of-Care Testing; Prospective Studies; Homosexuality, Male; Mass Screening; Trichomonas vaginalis; Sexually Transmitted Diseases; Trichomonas Vaginitis; Multicenter Studies as Topic; Sensitivity and Specificity; Adult; Point-of-Care Systems
PubMed: 38885995
DOI: 10.1136/bmjopen-2023-073565 -
Journal of Thoracic Disease May 2024Vascular rings represent 1% of congenital cardiovascular abnormalities. Phenotypic expression varies from asymptomatic to severe forms related to either oesophageal or...
BACKGROUND
Vascular rings represent 1% of congenital cardiovascular abnormalities. Phenotypic expression varies from asymptomatic to severe forms related to either oesophageal or tracheal compression. While refinement in prenatal screening led to an increase in fetal diagnosis, optimal management in asymptomatic neonates and infants is currently a matter of debate. We report our center experience of vascular ring management over three decades.
METHODS
In this single-center retrospective study, data were extracted from patient medical records. To obtain information on symptoms/medication at follow-up, clinical records from pediatric clinics were reviewed. For patients followed in other institutions, a web-based questionnaire was sent to referring pediatricians.
RESULTS
Out of 82 patients, 69 were symptomatic (84%). Common symptoms included recurrent respiratory tract infections (43%), stridor (32%), gastro-esophageal reflux (33%), and dysphagia (26%). Diagnosis relied on cardiac ultrasound, barium swallow studies, and chest computerized tomography scan. Surgical repair (thoracotomy 91%) was performed in 79 patients (96%). Median age at repair was 13 [interquartile range (IQR), 4.4-48] months. There was no mortality. Minor complications occurred in 14 patients (18%). Median hospital length of stay was 7 (IQR, 6-9) days. In total, 24% of patients remained symptomatic (median follow-up 54 months). Half of those were asthma-related, with nearly 90% freedom from ring-related symptoms.
CONCLUSIONS
Most patients were symptomatic at the time of diagnosis. Vascular rings such as pulmonary slings or tracheal compression syndromes require prompt management. Despite surgery, 24% of patients were not symptom-free at follow-up. Finally, surgery in asymptomatic patients resulted in low morbidity supporting the current recommendation of early surgical repair.
LEVEL OF EVIDENCE
III.
PubMed: 38883675
DOI: 10.21037/jtd-23-1526 -
Scientific Reports Jun 2024Enteric viral pathogens are associated with a significant burden of childhood morbidity and mortality. We investigated the relationship between viral pathogens and child...
Enteric viral pathogens are associated with a significant burden of childhood morbidity and mortality. We investigated the relationship between viral pathogens and child growth among under-5 children. We analyzed data from 5572/22,567 children enrolled in the Global Enteric Multicenter Study across seven study sites (2007-2011). Multiple linear regression was used to examine the association between the viral pathogens and changes of length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-scores, stratified by diarrheal symptoms and adjusted for potential covariates. Rotavirus (18.51%) and norovirus (7.33%) were the most prevalent enteric viral pathogens among symptomatic and asymptomatic under-5 children, respectively. Infection with individual enteric viral pathogens hurts child growth in asymptomatic children. However, the relationship with HAZ was less clear and statistically non-significant. On the other hand, the combined viral pathogens demonstrated a strong negative influence on child growth [WAZ: β coef.: - 0.10 (95%, CI - 0.15, - 0.05); P < 0.001 and WHZ: β: - 0.12 (95% CI - 0.17, - 0.07); P < 0.001] among asymptomatic children. Infection with any viral pathogen was associated with growth shortfalls [HAZ: β: - 0.05 (95% CI - 0.09, 0.00); P = 0.03 and WAZ: β: - 0.11 (95% CI - 0.16, - 0.07); P < 0.001 and WHZ: β: - 0.13 (95% CI - 0.18, - 0.09); P < 0.001], though the relationship with HAZ was less evident and became statistically non-significant in older children. Notably, among symptomatic children with moderate-to-severe diarrhea, individual enteric viral pathogens, as well as the combined effects of these pathogens [WHZ: β: 0.07; (95% CI 0.01, 0.14); P = 0.03] and the presence of any virus [HAZ: β: 0.09 (95% CI 0.05, 0.13) & WAZ: β: 0.08 (95% CI 0.03, 0.12); P < 0.001], exhibited positive effects on child growth. While previous studies hypothesized that several viral pathogens had a conflicting controversial role in child growth, we find clear indications that enteric viral pathogens are associated with growth shortfalls, specifically among asymptomatic children. These findings highlight the need for preventive strategies targeting children with enteric viral pathogens, which could address the consequences of growth faltering.
Topics: Humans; Infant; Child, Preschool; Female; Male; Africa South of the Sahara; Asia; Rotavirus; Diarrhea; Child Development; Norovirus; Rotavirus Infections; Infant, Newborn; Asia, Southern
PubMed: 38879558
DOI: 10.1038/s41598-024-64374-0 -
Journal of the Turkish German... Jun 2024In this study, maternal and neonatal outcomes of pregnant women with positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA tests were evaluated...
OBJECTIVE
In this study, maternal and neonatal outcomes of pregnant women with positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA tests were evaluated according to their symptomatic status. The clinical progression of SARS-CoV-2-positive pregnant women and the effect of coronavirus disease-2019 (COVID-19) on newborns was investigated.
MATERIAL AND METHODS
This retrospective cohort study was conducted at a tertiary pandemic hospital specializing in caring for pregnant women infected with SARS-CoV-2. We included patients with a positive SARS-CoV-2 polymerase chain reaction test at delivery, subdividing them into symptomatic and asymptomatic groups.
RESULTS
Two hundred and forty-nine patients were included in the study. The mean age of the pregnant women in the symptomatic group was higher than those in the asymptomatic group (p=0.001). The iatrogenic preterm birth rates in the symptomatic and asymptomatic groups were 43.37% and 8.43%, respectively (p<0.001). Cesarean section rate was higher in symptomatic group (p=0.01). Maternal death was significantly higher in symptomatic pregnant women (p<0.001). The neonatal intensive care unit admission rate was higher in symptomatic pregnant women (p<0.001).
CONCLUSION
The maternal and fetal outcomes for mothers with symptomatic infections tend to be worse, highlighting the importance of careful management, good follow-up and the advisability of closer monitoring.
PubMed: 38867711
DOI: 10.4274/jtgga.galenos.2024.2023-6-4