Use of Typhoid Vi-Polysaccharide Vaccine as a Vaccine Probe to Delineate Clinical Criteria for Typhoid Fever.

Abstract

Blood cultures (BCs) detect an estimated 50% of typhoid fever cases. There is need for validated clinical criteria to define cases that are BC negative, both to help direct empiric antibiotic treatment and to better evaluate the magnitude of protection conferred by typhoid vaccines. To derive and validate a clinical rule for defining BC-negative typhoid fever, we assessed, in a cluster-randomized effectiveness trial of Vi-polysaccharide (ViPS) typhoid vaccine in Kolkata, India, 14,797 episodes of fever lasting at least 3 days during 4 years of comprehensive, BC-based surveillance of 70,865 persons. A recursive partitioning algorithm was used to develop a decision rule to predict BC-proven typhoid cases with a diagnostic specificity of 97-98%. To validate this rule as a definition for BC-negative typhoid fever, we assessed whether the rule defined culture-negative syndromes prevented by ViPS vaccine. In a training subset of individuals, we identified the following two rules: rule 1: patients aged < 15 years with prolonged fever accompanied by a measured body temperature ≥ 100°F, headache, and nausea; rule 2: patients aged ≥ 15 years with prolonged fever accompanied by nausea and palpable liver but without constipation. The adjusted protective efficacy of ViPS against clinical typhoid defined by these rules in persons aged ≥ 2 years in a separate validation subset was 33% (95% CI: 4-53%). We have defined and validated a clinical rule for predicting BC-negative typhoid fever using a novel vaccine probe approach. If validated in other settings, this rule may be useful to guide clinical care and to enhance typhoid vaccine evaluations.

• Authors: Md Taufiqul Islam, Justin Im, Faisal Ahmmed, Deok Ryun Kim, Ashraful Islam Khan, Khalequ Zaman, Mohammad Ali, Florian Marks, Firdausi Qadri, Jerome H Kim, John D Clemens
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 103 Issue 2 Pg. 665-671 (08 2020) ISSN: 1476-1645 [Electronic] United States
• PMID: 32588803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Polysaccharides, Bacterial
• Typhoid-Paratyphoid Vaccines
• Vi polysaccharide vaccine, typhoid

Topics

• Adolescent
• Adult
• Algorithms
• Blood Culture
• Child
• Child, Preschool
• Clinical Decision Rules
• Decision Trees
• Fever (physiopathology)
• Headache (physiopathology)
• Humans
• India
• Liver (pathology)
• Machine Learning
• Nausea (physiopathology)
• Palpation
• Polysaccharides, Bacterial (therapeutic use)
• Randomized Controlled Trials as Topic
• Sensitivity and Specificity
• Time Factors
• Typhoid Fever (diagnosis, physiopathology, prevention & control)
• Typhoid-Paratyphoid Vaccines (therapeutic use)
• Young Adult