Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.

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.

Cushing syndrome after bilateral lensectomy.

UNLABELLED: Iatrogenic Cushing syndrome induced by oral and parenteral corticosteroid administration is a well-known complication, and necessary precautions have to be taken. Cushing syndrome, however, following treatment with glucocorticoid-containing eye drops is a very rare complication. To the best of our knowledge, there have been only four reported cases in the literature. Herein, we present an infant boy who developed Cushing syndrome after receiving dexamethasone-containing eye drops after bilateral cataract extraction to prevent postoperative inflammatory complications. At the age of 5 months, after approx. 3 months of dexamethasone therapy, the patient presented with cushingoid facies, nephrocalcinosis and failure to grow. Iatrogenic Cushing syndrome was diagnosed and dexamethasone-containing eye drops were reduced and eventually stopped. Follow-up examinations revealed catch-up growth. CONCLUSION: Ocularly administered corticosteroids may have substantial systemic side effects in infants.

Case report: narcolepsy type 1 in an adolescent with HIV infection-coincidence or potential trigger?

RATIONALE: Despite the acknowledged importance of environmental risk factors in the etiology of narcolepsy, there is little research on this topic. HIV as a trigger for narcolepsy has not been systematically investigated. PATIENT CONCERNS: We describe a case of narcolepsy type 1 (NT1) in an adolescent with HIV infection presenting with increased daytime sleepiness and excessive weight gain. DIAGNOSES: NT1 was diagnosed according to the criteria of the third edition of the International Classification of Sleep Disorders (ICSD-3). INTERVENTIONS: Pharmacological treatment with methylphenidate. OUTCOMES: Four months after initiation of methylphenidate therapy the increased daytime sleepiness improved and excessive weight gain stopped. LESSONS: Diagnosis of NT1 can be challenging at disease onset and is often delayed, especially in the pediatric population, because symptoms usually evolve gradually. The case presented here raises the possibility that the HIV infection may play a role in the pathogenesis of NT1 serving as trigger for autoimmune-mediated destruction of hypocretin-secreting neurons.