Phase 3 trial shows safety, high efficacy of typhoid conjugate vaccine
A phase 3 clinical trial conducted in Malawi has found that a single dose of typhoid conjugate vaccine (TCV) is safe and more than 80% effective at protecting children against typhoid fever, an international team of researchers reported yesterday in the New England Journal of Medicine.
In the randomized, double-blind trial, investigators assigned children from 9 months to 12 years of age in a 1:1 ratio to receive a single dose of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV) or meningococcal capsular group A conjugate (MenA) vaccine as the control group. The primary outcome was typhoid fever by confirmed blood culture. Vaccine efficacy and safety outcomes were reported after 18 to 24 months of follow-up.
A total of 28,130 children were included in the intention-to-treat analysis, with 14,069 assigned to Vi-TCV and 14,061 to MenA. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV arm (46.9 cases per 100,000 children) and in 62 children in the MenA arm (243.2 cases per 100,000). The protective efficacy against culture-confirmed typhoid fever at any time after vaccination was 80.7% (95% confidence interval [CI], 64.2% to 89.6%) in the intention-to-treat analysis and 83.7% (95% CI, 68.1% to 91.6%) in the per-protocol analysis. The efficacy was similar in children 5 years and younger and those 5 years and older.
In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths, all in the MenA group. No serious adverse events were considered by the trial investigators to be related to vaccination.
The investigators say the findings are critical given that several multidrug-resistant strains of typhoid fever, which is caused by Salmonella enterica serovar Typhi, have emerged in Malawi and eastern and southern Africa, making treatment more challenging. They note that 100% of typhoid fever samples among the children in the trial were resistant to first-line antibiotics, and four Salmonella Typhi strains showed reduced susceptibility to fluoroquinolones.
“Our only real option to controlling these new resistant strains of typhoid in a timely way is through the vaccine,” lead investigator Melita Gordon, MD, of the University of Liverpool and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme, said in a university press release.
Multifaceted primary care stewardship tied to fewer prescribed antibiotics
A randomized trial conducted in Ontario found that a multifaceted antibiotic stewardship intervention implemented in primary care practices was associated with reduced likelihood of antibiotic prescriptions for urinary tract and respiratory infections, researchers reported this week in BMC Family Practice.
In the pragmatic trial, practitioners from six primary care clinics in Toronto were assigned to a control group or an intervention group to evaluate the effectiveness of the intervention, which involved clinician education, clinical decision aids for prescribing decisions, patient information leaflets, audit and feedback of clinic prescription practices, local clinic support, and incentives. The primary outcome was total antibiotic prescriptions for urinary tract and respiratory infections, and secondary outcomes included delayed prescriptions, prescriptions lasting longer than 7 days, and use of recommended antibiotic.
There were 1,682 encounters involving 54 primary care providers from January until May 31, 2019. After adjustment for characteristics associated with antibiotic prescription, the odds of any antibiotic prescription were reduced by 22% (adjusted odds ratio [OR], 0.78; 95% CI, 0.64 to 0.96) in intervention clinics compared with control clinics.
The odds that a delay in filling a prescription was recommended at an intervention clinic was increased (adjusted OR, 2.29; 95% CI, 1.37 to 3.83), while prescription durations greater than 7 days were reduced (adjusted OR, 0.24; 95% CI, 0.13 to 0.43). Recommended antibiotic use was similar in control (85.4%) and intervention clinics (91.8%).
“This study has demonstrated that clinically important changes in antibiotic utilization in primary care clinics are possible with local stewardship efforts involving provider-focused education, clinical decision aids, clinic support, ongoing audit and feedback, and compensation for [antimicrobial stewardship] activities,” the study authors wrote. “Structured and supported community-based antimicrobial stewardship efforts, similar to those in hospital settings, warrant further study.”
Sep 15 BMC Fam Pract study