Typhoid conjugate vaccines: making vaccine history in Africa

Meiring, James; Patel, Pratiksha; Patel, Priyanka; Gordon, Michael A.

doi:10.1080/14760584.2018.1496825

Cited by 12 publications

(11 citation statements)

References 21 publications

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“…With the emergence of substantial drug resistance in S. Typhi, good surveillance data to support interventions with the available typhoid vaccine as well as treatment strategies are crucial. It is further expected that, with the rollout of the typhoid vaccine and the resulting decreased burden of typhoidal Salmonella, non-typhoidal Salmonella will become the most frequent form of salmonellosis, supporting the observed prioritization [42][43][44]. Notably, B. pseudomallei was given specific attention in the "MSF-use case".…”

Section: Discussionmentioning

confidence: 92%

Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries

et al. 2020

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Background: Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens. Method: A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated. Results: The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidal Salmonella, Plasmodium species and Mycobacterium tuberculosis as the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients. Conclusion: This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, combining available prevalence data with expert input, can result in a broadly applicable priority list. This comprehensive utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.

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Section: Discussionmentioning

confidence: 92%

Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries

et al. 2020

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Section: Discussionmentioning

confidence: 96%

Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries

Osborn¹,

Roberts²,

Guillén

et al. 2019

Preprint

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Background: Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens. Method: A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated. Results: The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidal Salmonella , Plasmodium species and Mycobacterium tuberculosis as the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients. Conclusion: This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, including the actionability, can result in a broadly applicable priority list. This broad utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.

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“…In summary, the Typbar-TCV Vi conjugate vaccine is a promising candidate for the control of typhoid fever in Africa, because of its 1-dose schedule and its demonstrated immunogenicity and safety profile in children. To date, no studies of the field efficacy of any TCV have been conducted in Africa [30]. This protocol is designed to demonstrate the impact of Vi-TCV in an endemic setting in Malawi.…”

mentioning

confidence: 99%

Typhoid Vaccine Acceleration Consortium Malawi: A Phase III, Randomized, Double-blind, Controlled Trial of the Clinical Efficacy of Typhoid Conjugate Vaccine Among Children in Blantyre, Malawi

Meiring

Laurens

Patel

et al. 2019

Clinical Infectious Diseases

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Background Typhoid fever is an acute infection characterized by prolonged fever following the ingestion and subsequent invasion of Salmonella enterica serovar Typhi ( S. Typhi), a human-restricted pathogen. The incidence of typhoid fever has been most reported in children 5–15 years of age, but is increasingly recognized in children younger than 5 years old. There has been a recent expansion of multidrug-resistant typhoid fever globally. Prior typhoid vaccines were not suitable for use in the youngest children in countries with a high burden of disease. This study aims to determine the efficacy of a typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization, by testing it in children 9 months through 12 years of age in Blantyre, Malawi. Methods In this Phase III, individually randomized, controlled, double-blind trial of the clinical efficacy of TCV, 28 000 children 9 months through 12 years of age will be enrolled and randomized in a 1:1 ratio to receive either Vi-TCV or a meningococcal serogroup A conjugate vaccine. A subset of 600 of these children will be further enrolled in an immunogenicity and reactogenicity sub-study to evaluate the safety profile and immune response elicited by Vi-TCV. Recruiting began in February 2018. Results All children will be under passive surveillance for at least 2 years to determine the primary outcome, which is blood culture–confirmed S. Typhi illness. Children enrolled in the immunogenicity and reactogenicity sub-study will have blood drawn before vaccination and at 2 timepoints after vaccination to measure their immune response to vaccination. They will also be followed actively for adverse events and serious adverse events. Conclusions The introduction of a single-dose, efficacious typhoid vaccine into countries with high burden of disease or significant antimicrobial resistance could have a dramatic impact, protecting children from infection and reducing antimicrobial usage and associated health inequity in the world’s poorest places. This trial, the first of a TCV in Africa, seeks to demonstrate the impact and programmatic use of TCVs within an endemic setting. Clinical Trials Registration NCT03299426.

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Typhoid conjugate vaccines: making vaccine history in Africa

Cited by 12 publications

References 21 publications

Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries

Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries

Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries

Typhoid Vaccine Acceleration Consortium Malawi: A Phase III, Randomized, Double-blind, Controlled Trial of the Clinical Efficacy of Typhoid Conjugate Vaccine Among Children in Blantyre, Malawi

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