Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial

Shakya, Mila; Voysey, Merryn; Theiss-Nyland, Katherine; Colin-Jones, Rachel; Pant, Dikshya; Adhikari, Anup; Tonks, Susan; Mujadidi, Yama F; O’Reilly, Peter; Mazur, Olga; Kelly, Sarah; Liu, Xinxue; Maharjan, Anjana; Dahal, Ashata; Haque, Naheeda; Pradhan, Anisha; Shrestha, Suchita; Joshi, Manij; Smith, N.; Hill, Jennifer; Clarke, Jenny; Stockdale, Lisa; Jones, Elizabeth; Lubinda, Timothy; Bajracharya, Binod; Dongol, Sabina; Karkey, Abhilasha; Baker, Stephen; Dougan, Gordan; Pitzer, Virginia E.; Neuzil, Kathleen M.; Shrestha, Shrijana; Basnyat, Buddha; Pollard, Andrew J.

doi:10.1016/s2214-109x(21)00346-6

Cited by 60 publications

(56 citation statements)

References 21 publications

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“…71,72 New data available from the two-year follow-up of the randomized-controlled trial in Nepal revealed a protective efficacy against blood-culture confirmed typhoid fever of 79.0% (95% CI, 61.9-88.5%). 73 These results were comparable to those from the interim analysis, which collectively indicate long-term vaccine protection and provide further support for its use in typhoid-endemic regions. Further, results also showed that the Vi-TT-TCV performed consistently well across different regions, populations and transmission settings with a robust safety profile.…”

Section: Typhoid Vaccines: Recent Developmentssupporting

confidence: 75%

The Burden of Typhoid Fever in Sub-Saharan Africa: A Perspective

Kim¹,

Espinoza²,

Vannice³

et al. 2022

RRTM

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While typhoid fever has largely been eliminated in high-income regions which have developed modern water, sanitation, and hygiene facilities, it remains a significant public health burden resulting in morbidity and mortality among millions of individuals in resource-constrained settings. Prevention and control efforts are needed that integrate several high-impact interventions targeting facilities and infrastructure, including those addressing improvements in sanitation, access to safe water, and planned urbanization, together with parallel efforts directed at effective strategies for use of typhoid conjugate vaccines (TCV). The use of TCVs is a critical tool with the potential of having a rapid impact on typhoid fever disease burden; their introduction will also serve as an important strategy to combat evolving antimicrobial resistance to currently available typhoid fever treatments. Well-designed epidemiological surveillance studies play a critical role in establishing the need for, and monitoring the impact of, typhoid fever control and prevention strategies implemented by public health authorities. Here, we present a perspective based on a narrative review of the impact of typhoid fever on morbidity and mortality in sub-Saharan Africa and discuss ongoing surveillance activities and the role of vaccination in prevention and control efforts.

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Section: Typhoid Vaccines: Recent Developmentssupporting

confidence: 75%

The Burden of Typhoid Fever in Sub-Saharan Africa: A Perspective

Kim¹,

Espinoza²,

Vannice³

et al. 2022

RRTM

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“…Fields trials have since been underway in countries with high burden of disease and/or high rates of antimicrobial resistance ( Neuzil et al, 2020 ). Recently, the result of an efficacy of Vi-TT vaccine in Nepal was reported ( Shakya et al, 2021 ). The field trial enrolled 20,019 children aged 9 months to 16 years who received a single dose of TCV or capsular group A meningococcal conjugate vaccine (MenA).…”

Section: Evaluation Of Typhoid Vaccine Candidates Using Chimmentioning

confidence: 99%

“…The field trial enrolled 20,019 children aged 9 months to 16 years who received a single dose of TCV or capsular group A meningococcal conjugate vaccine (MenA). The group reported a protective efficacy of 79% against blood culture confirmed typhoid fever at 2 years ( Shakya et al, 2021 ). Similar results were observed in children participating in a large field study in Bangladesh ( Qadri et al, 2021 ).…”

Section: Evaluation Of Typhoid Vaccine Candidates Using Chimmentioning

confidence: 99%

Controlled human infectious models, a path forward in uncovering immunological correlates of protection: Lessons from enteric fevers studies

Sztein

Booth²

2022

Front. Microbiol.

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Enteric infectious diseases account for more than a billion disease episodes yearly worldwide resulting in approximately 2 million deaths, with children under 5 years old and the elderly being disproportionally affected. Enteric pathogens comprise viruses, parasites, and bacteria; the latter including pathogens such as Salmonella [typhoidal (TS) and non-typhoidal (nTS)], cholera, Shigella and multiple pathotypes of Escherichia coli (E. coli). In addition, multi-drug resistant and extensively drug-resistant (XDR) strains (e.g., S. Typhi H58 strain) of enteric bacteria are emerging; thus, renewed efforts to tackle enteric diseases are required. Many of these entero-pathogens could be controlled by oral or parenteral vaccines; however, development of new, effective vaccines has been hampered by lack of known immunological correlates of protection (CoP) and limited knowledge of the factors contributing to protective responses. To fully comprehend the human response to enteric infections, an invaluable tool that has recently re-emerged is the use of controlled human infection models (CHIMs) in which participants are challenged with virulent wild-type (wt) organisms. CHIMs have the potential to uncover immune mechanisms and identify CoP to enteric pathogens, as well as to evaluate the efficacy of therapeutics and vaccines in humans. CHIMs have been used to provide invaluable insights in the pathogenesis, host-pathogen interaction and evaluation of vaccines. Recently, several Oxford typhoid CHIM studies have been performed to assess the role of multiple cell types (B cells, CD8+ T, Tregs, MAIT, Monocytes and DC) during S. Typhi infection. One of the key messages that emerged from these studies is that baseline antigen-specific responses are important in that they can correlate with clinical outcomes. Additionally, volunteers who develop typhoid disease (TD) exhibit higher levels and more activated cell types (e.g., DC and monocytes) which are nevertheless defective in discrete signaling pathways. Future critical aspects of this research will involve the study of immune responses to enteric infections at the site of entry, i.e., the intestinal mucosa. This review will describe our current knowledge of immunity to enteric fevers caused byS. Typhi and S. Paratyphi A, with emphasis on the contributions of CHIMs to uncover the complex immunological responses to these organisms and provide insights into the determinants of protective immunity.

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“…A single dose of Typbar-TCV ® , the first prequalified Vi conjugate, was 79–95% effective in preventing typhoid fever following immunization of infants, children, and young adults. 5 – 10 However, even if high vaccination coverage substantially reduces the incidence of typhoid, 5 – 10 for some years chronic S. Typhi carriers will remain within the population constituting a reservoir of infection that can be transmitted. Ideally, chronic carriers can be systematically identified (by stool culture and IgG Vi antibody titer) and treated if the antimicrobial susceptibility of the endemic strain(s) allows.…”

Section: Introductionmentioning

confidence: 99%

Point-of-Care Ultrasound by Nonexpert Operators Demonstrates High Sensitivity and Specificity in Detecting Gallstones: Data from the Samoa Typhoid Fever Control Program

Hoffman

Desai

Sikorski

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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Approximately 90% of chronic typhoid carriers with persistent Salmonella enterica serovar Typhi (S. Typhi) gallbladder infection have gallstones. In Samoa, where typhoid fever has been endemic for many decades, risk factors predisposing to the development of gallstones are increasing among adults. The Samoa Typhoid Fever Control Program dispatches a “Typhoid Epidemiologic SWAT Team” to perform a household investigation of every blood culture-confirmed case of acute typhoid fever. Investigations include screening household contacts to detect chronic carriers. Following limited training, two nonexpert ultrasound operators performed point-of-care ultrasound (POCUS) on 120 Samoan adults from August to September 2019 to explore the feasibility of POCUS to detect individuals with gallstones during household investigations and community screenings. POCUS scans from 120 Samoan adults in three cohorts (28 food handlers, two typhoid cases and their 18 household contacts, and 72 attendees at an ambulatory clinic) were reviewed by a board-certified radiologist who deemed 96/120 scans (80%) to be interpretable. Compared with the radiologist (gold standard), the nonexpert operators successfully detected 6/7 Samoans with gallstones (85.7% sensitivity) and correctly identified 85/89 without gallstones (95.5% specificity). The proportion (24/120) of uninterpretable scans from this pilot that used minimally trained clinicians (who are neither radiologists nor ultrasound technicians) indicates the need for additional training of POCUS operators. Nevertheless, this pilot feasibility study engenders optimism that in the Samoan setting nonexperts can be trained to use POCUS to diagnose cholelithiasis, thereby helping (along with stool cultures and Vi serology) to identify possible chronic S. Typhi carriers.

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Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial

Cited by 60 publications

References 21 publications

The Burden of Typhoid Fever in Sub-Saharan Africa: A Perspective

The Burden of Typhoid Fever in Sub-Saharan Africa: A Perspective

Controlled human infectious models, a path forward in uncovering immunological correlates of protection: Lessons from enteric fevers studies

Point-of-Care Ultrasound by Nonexpert Operators Demonstrates High Sensitivity and Specificity in Detecting Gallstones: Data from the Samoa Typhoid Fever Control Program

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