Genomic characterization of endemic diarrheagenic Escherichia coli and Escherichia albertii from infants with diarrhea in Vietnam.

BACKGROUND: Diarrheagenic Escherichia coli (DEC) is a group of bacterial pathogens that causes life-threatening diarrhea in children in developing countries. However, there is limited information on the characteristics of DEC isolated from patients in these countries. A detailed genomic analysis of 61 DEC-like isolates from infants with diarrhea was performed to clarify and share the characteristics of DEC prevalent in Vietnam. PRINCIPAL FINDINGS: DEC was classified into 57 strains, including 33 enteroaggregative E. coli (EAEC) (54.1%), 20 enteropathogenic E. coli (EPEC) (32.8%), two enteroinvasive E. coli (EIEC) (3.3%), one enterotoxigenic E. coli (ETEC), and one ETEC/EIEC hybrid (1.6% each), and surprisingly into four Escherichia albertii strains (6.6%). Furthermore, several epidemic DEC clones showed an uncommon combination of pathotypes and serotypes, such as EAEC Og130:Hg27, EAEC OgGp9:Hg18, EAEC OgX13:H27, EPEC OgGp7:Hg16, and E. albertii EAOg1:HgUT. Genomic analysis also revealed the presence of various genes and mutations associated with antibiotic resistance in many isolates. Strains that demonstrate potential resistance to ciprofloxacin and ceftriaxone, drugs recommended for treating childhood diarrhea, accounted for 65.6% and 41%, respectively. SIGNIFICANCE: Our finding indicate that the routine use of these antibiotics has selected resistant DECs, resulting in a situation where these drugs do not provide in therapeutic effects for some patients. Bridging this gap requires continuous investigations and information sharing regarding the type and distribution of endemic DEC and E. albertii and their antibiotic resistance in different countries.

The efficacy, safety and immunogenicity Nanocovax: results of a randomized, double-blind, placebo-controlled Phase 3 trial.

BackgroundNanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant. In a Phase 1 and 2 studies, (NCT04683484) the vaccine was found to be safe and induce a robust immune response in healthy adult participants. MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, immunogenicity, and protective efficacy of the Nanocovax vaccine against Covid-19 in approximately 13,007 volunteers aged 18 years and over. The immunogenicity was assessed based on Anti-S IgG antibody response, surrogate virus neutralization, wild-type SARS-CoV-2 neutralization and the types of helper T-cell response by intracellular staining (ICS) for interferon gamma (IFNg) and interleukin-4 (IL-4). The vaccine efficacy (VE) was calculated basing on serologically confirmed cases of Covid-19. FindingsUp to day 180, incidences of solicited and unsolicited adverse events (AE) were similar between vaccine and placebo groups. 100 serious adverse events (SAE) were observed in both vaccine and placebo groups (out of total 13007 participants). 96 out of these 100 SAEs were determined to be unrelated to the investigational products. 4 SAEs were possibly related, as determined by the Data and Safety Monitoring Board (DSMB) and investigators. Reactogenicity was absent or mild in the majority of participants and of short duration. These findings highlight the excellent safety profile of Nanocovax. Regarding immunogenicity, Nanocovax induced robust IgG and neutralizing antibody responses. Importantly, Anti S-IgG levels and neutralizing antibody titers on day 42 were higher than those of natural infected cases. Nanocovax was found to induce Th2 polarization rather than Th1. Post-hoc analysis showed that the VE against symptomatic disease was 51.5% (95% confidence interval [CI] was [34.4%-64.1%]. VE against severe illness and death were 93.3% [62.2-98.1]. Notably, the dominant strain during the period of this study was Delta variant. InterpretationNanocovax 25 microgram (mcg) was found to be safe with the efficacy against symptomatic infection of Delta variant of 51.5%. FundingResearch was funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of Vietnam; ClinicalTrials.gov number, NCT04922788.

Emotional quality-of-life and patient-reported limitation in sports participation in children with uncorrected congenital and acquired heart disease in healthcare-restricted settings in low- and middle-income countries.

BACKGROUND: Little is known about emotional quality-of-life in paediatric heart disease in low- and middle-income countries where the prevalence of uncorrected lesions is high. Research on emotional quality-of-life and its predictors in these settings is key to planning interventions. METHODS: Ten-year retrospective cross-sectional study of children aged 6-17 years with uncorrected congenital or acquired heart disease in 12 low- and middle-income countries was conducted. Emotional functioning score of the PedsQL TM 4.0 generic core scale and data on patient-reported limitation in sports participation were collected via in-person interview and analysed using regression analyses. RESULTS: Ninety-four children reported mean emotional functioning scores of 71.94 (SD 25.32) [95% CI 66.75-77.13] with lower scores independently associated with having a parent with a chronic illness or who had died (p = 0.005), having less than three siblings (p = 0.007), and reporting a subjective limitation in carrying an item equivalent to a 4 lb load (p = 0.021). Patient-reported limitation in sports participation at least "sometimes" was present in 69% and was independently associated with experiencing symptoms at least once a month (p < 0.001). CONCLUSION: Some of the factors which were associated with better emotional quality-of-life were similar to those identified in previous studies in patients with corrected defects. Patient-reported limitation in sports participation is common. In addition to corrective surgery and exercise, numerous other interventions which are practicable during surgical missions might improve emotional quality-of-life.

A dose-escalation safety and immunogenicity study of a new live attenuated human rotavirus vaccine (Rotavin-M1) in Vietnamese children.

We tested a candidate live, oral, rotavirus vaccine (Rotavin-M1™) derived from an attenuated G1P [8] strain (KH0118-2003) isolated from a child in Vietnam. The vaccine was tested first for safety in 29 healthy adults. When deemed safe, it was further tested for safety and immunogenicity in 160 infants (4 groups) aged 6-12 weeks in a dose and schedule ranging study. The vaccine was administered in low titer (10(6.0)FFU/dose) on a 2-dose schedule given 2 months apart (Group 2L) and on a 3-dose schedule given 1 month apart (Group 3L) and in high titer (10(6.3)FFU/dose) in 2 doses 2 months apart (Group 2H) and in 3 doses 1 month apart (Group 3H). For comparison, 40 children (group Rotarix™) were given 2 doses of the lyophilized Rotarix™ vaccine (10(6.5)CCID(50)/dose) 1 month apart. All infants were followed for 30 days after each dose for clinical adverse events including diarrhea, vomiting, fever, abdominal pain, irritability and intussusception. Immunogenicity was assessed by IgA seroconversion and viral shedding was monitored for 7 days after administration of each dose. Two doses of Rotavin-M1 (10(6.3)FFU/dose) were well tolerated in adults. Among infants (average 8 weeks of age at enrollment), administration of Rotavin-M1 was safe and did not lead to an increased rate of fever, diarrhea, vomiting or irritability compared to Rotarix™, indicating that the candidate vaccine virus had been fully attenuated by serial passages. No elevation of levels of serum transaminase, blood urea, or blood cell counts were observed. The highest rotavirus IgA seroconversion rate (73%, 95%CI (58-88%)) was achieved in group 2H (2 doses--10(6.3)FFU/dose, 2 months apart). The 2 dose schedules performed slightly better than the 3 dose schedules and the higher titer doses performed slightly better than the lower titer doses. These rates of seroconversion were similar to that of the Rotarix™ group (58%, 95%CI (42-73%)). However more infants who received Rotarix™ (65%) shed virus in their stool after the first dose than those who received Rotavin-M1 (44-48%) (p<0.05) and the percent shedding decreased after subsequent doses of either vaccine. Rotavin-M1 vaccine is safe and immunogenic in Vietnamese infants. A trial in progress will assess the safety, immunogenicity and efficacy of Rotavin-M1 (2 doses at 10(6.3)FFU/dose) in a larger number of infants. The trial registration numbers are NCT01375907 and NCT01377571.