ArticlePloS one2018
Clinical endpoints in the controlled human challenge model for Shigella: A call for standardization and the development of a disease severity score.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06615375 (Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study With the Shigella Tetravalent Bioconjugate Vaccine Shigella4V2), which is not on this map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study With the Shigella Tetravalent Bioconjugate Vaccine Shigella4V2
Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Development of a new travellers' diarrhoea clinical severity classification and its utility in confirming rifamycin-SV efficacy.Journal of travel medicine · 2023Trial
- Symptoms and adverse events in controlled human infection models.Frontiers in medicine · 2025Review
- Shigella-Controlled Human Infection Models: Current and Future Perspectives.Current topics in microbiology and immunology · 2024Review
- Systems approach to define humoral correlates of immunity to Shigella.Cell reports · 2022Article
- A disease severity scale for the evaluation of vaccine and other preventive or therapeutic interventions for travellers' diarrhoea.Journal of travel medicine · 2022Article
- Shigella conjugate vaccine efficacy trial in controlled human model and potential immune correlates of protection.EBioMedicine · 2021Article
- Immune Response Characterization after Controlled Infection with Lyophilized Shigella sonnei 53G.mSphere · 2020Article
- Establishment of a Controlled Human Infection Model with a Lyophilized Strain of Shigella sonnei 53G.mSphere · 2020Article
- An Oral Inoculation Infant Rabbit Model formBio · 2020Article
- Challenges for Clinical Development of Vaccines for Prevention of Hospital-Acquired Bacterial Infections.Frontiers in immunology · 2020Review
- Functional antibodies as immunological endpoints to evaluate protective immunity againstHuman vaccines & immunotherapeutics · 2020Review
- Consensus Report on Shigella Controlled Human Infection Model: Clinical Endpoints.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Consensus Report on Shigella Controlled Human Infection Model: Conduct of Studies.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Classical and novel strategies to develop aHuman vaccines & immunotherapeutics · 2019Review
- Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundSince 1946 the controlled human infection model (CHIM) for Shigella has been used to improve understanding of disease pathogenesis, describe clinical and immunologic responses to infection and as a tool for vaccine development. As the frequency and intent for use in vaccine comparisons increases, standardization of the primary endpoint definition is necessary.
methodsSubject-level data were obtained from previously conducted experimental Shigella CHIM studies. Signs and symptoms severity were categorized consistently across all studies. Sign and symptom correlations were estimated and univariate models were utilized to describe the association between stool output and other Shigella-attributable signs and symptoms. Multiple correspondence and hierarchical clustering analyses were performed to describe the co-occurrence of signs and symptoms. A disease score is proposed based on the co-occurrence of these events.
resultsData were obtained on 54 subjects receiving 800 to 2000 colony forming units (cfu) of S. flexneri. The median maximum 24 hour stool output was 514 ml (IQR: 300, 998 ml) with a median frequency of 6 (IQR: 4, 9). Subjects reported abdominal pain or cramps (81.5%), headache (66.7%) and anorexia (64.8%), 50.0% had a fever and 27.8% had gross blood in multiple loose stools. Multiple correspondence analyses highlighted co-occurrence of symptoms based on severity. A 3-parameter disease severity score predicted shigellosis endpoints and better differentiated disease spectrum.
conclusionDichotomous endpoints for Shigella CHIM fail to fully account for disease variability. An ordinal disease score characterizing the breadth of disease severity may enable a better characterization of shigellosis and can decrease sample size requirements. Furthermore, the disease severity score may be a useful tool for portfolio management by enabling prioritization across vaccine candidates with comparable efficacy estimates using dichotomous endpoints.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.