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Background: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings.Methods: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110.Findings: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed.Interpretation: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses.Funding: The study was funded by the Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Background Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds. Methods In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850. Findings Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1•2, 95% CI 0•8-1•7) or MenACWY-CRM (0•9, [0•6-1•3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18•2% [95% CI 3•4-30•8] carriage reduction), capsular groups BCWY (26•6% [10•5-39•9] carriage reduction), capsular groups CWY (29•6% [8•1-46•0] carriage reduction), and serogroups CWY (28•5% [2•8-47•5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39•0% (95% CI 17•3-55•0) carriage reduction for serogroup Y and 36•2% (15•6-51•7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified. Interpretation Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented. Funding Novartis Vaccines. [ABSTRACT FROM AUTHOR]

This article reports the results of a clinical trial comparing the safety and effectiveness of a second-generation, inactivated candidate vaccine for Japanese encephalitis with a mouse-brain-derived vaccine. Japanese encephalitis is a major caused of encephalitis in Asia causing about 50,000 deaths per year mostly in children under the age of 10. Only one vaccine is licensed in the U.S. and none are licensed in Europe. The study compared the Vero-cell derived vaccine with the licensed vaccine and found the safety profile of the test vaccine was good with better tolerability than the licensed vaccine. Adverse effects were similar in both groups. The test vaccine was found to provide good protection against the disease.

Background: In China, since 1989, an estimated 120 million children have been immunised with the SA 14-14-2 live-attenuated Japanese encephalitis (JE) vaccine at ages 1, 2, and 6 years. A case-control study of licensed vaccine found two doses to be 98% effective. Subsequently, researchers found that single-dose vaccine efficacy was high; we aimed to confirm this result.Methods: During July 11-24, 1999, 160000 doses of JE vaccine were given to children aged 1-15 years, resident in three districts of Nepal. Several cases of JE were admitted to hospital from early August. We obtained names and addresses of cases with serological evidence of a recent infection from Bheri Zonal Hospital, Nepalgunj. We did a matched case-control study and calculated the odds ratio of vaccination among JE cases and age-sex matched village controls.Findings: 20 children, aged 1-15 years, were identified whose illness conformed with the JE case definition and were resident in villages receiving the vaccine. None of 20 JE cases had received JE vaccine compared with 326 of 557 age-sex matched village controls. The efficacy of a single dose of JE vaccine was 99.3% (CI 94.9-100%).Interpretation: A single dose of JE vaccine is highly efficacious in preventing Japanese encephalitis when administered only days or weeks before exposure to infection. [ABSTRACT FROM AUTHOR]

Presents a study which sought to measure the effectiveness of an inexpensive live-attenuated vaccine (SA14-14-2) introduced in China in 1988, to immunize against Japanese encephalitis. How many susceptible individuals remain unimmunized; Patients and methods; Findings and interpretation; Conclusion and discussion.

This article comments on a study in this issue which offers promise of a Japanese encephalitis vaccine derived from Vero cells. Japanese encephalitis virus is a mosquito borne flavivirus that causes about 50,000 deaths a year. There was a vaccine for this disease that Japan pulled off the market following a case of acute disseminated encephalomyelitis in a person who got the vaccine. The authors warn that as promising as the research is, some caution is warranted.

The article focuses on the protection of children against Japanese encephalitis in Bali, Indonesia. Topics discussed include an overview of Japanese encephalitis, its diagnosis, the presence of the disease, its prevalence and transmission, the significance of its vaccination programme, and the community-based mass campaign for the programme.

Reports that a number of children in China were hospitalized after reportedly developing side effects related to vaccination against Japanese encephalitis. Symptoms of the children; Anger of parents at the adverse events experienced by their children; Population control in China; Transmission of the disease by mosquitoes; Idea that the outbreak in the children was psychogenic in origin.

Reports on the reversal of the Australian government's decision to ban the use of vaccines against Japanese B encephalitis (JE). Affected population; Areas affected; Complications; Mortality rate; Licensing of the vaccine.