Operational challenges and lessons learned from conducting febrile surveillance in a long-term randomized dengue vaccine trial in Latin America and Asia-Pacific
Background: In trials, dengue vaccine efficacy evaluation relies on participants presenting with febrile illness/clinically suspected dengue contacting the study site for sample collection and clinical assessment within a short timeframe. Here, we present key considerations to maintain high complian...
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Elsevier
2025-05-01
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| Series: | Travel Medicine and Infectious Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1477893925000468 |
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| author | Harald Pfaar Eduardo López-Medina Ian Escudero Yanee Hutagalung Nicholas Roubinis Seloni Thakrar Charissa Fay Corazon Borja-Tabora Vianney Tricou Suely Tuboi |
| author_facet | Harald Pfaar Eduardo López-Medina Ian Escudero Yanee Hutagalung Nicholas Roubinis Seloni Thakrar Charissa Fay Corazon Borja-Tabora Vianney Tricou Suely Tuboi |
| author_sort | Harald Pfaar |
| collection | DOAJ |
| description | Background: In trials, dengue vaccine efficacy evaluation relies on participants presenting with febrile illness/clinically suspected dengue contacting the study site for sample collection and clinical assessment within a short timeframe. Here, we present key considerations to maintain high compliance with the febrile surveillance procedures in a trial that assessed TAK-003 efficacy. Methods: DEN-301 (NCT02747927) is a randomized phase 3 trial in children/adolescents from eight dengue-endemic countries in Latin America (LATAM) and Asia-Pacific (APAC). Febrile surveillance consisted of weekly contact with the participant to identify cases of fever (≥38 °C; two of three consecutive days). Blood samples were collected for molecular testing, preferably ≤5 days of fever onset, together with thorough clinical assessment by the investigators. The data are presented descriptively. Results: Of the 20,071 (LATAM, 11,080; APAC, 8991) participants who received TAK-003/placebo, 18,260 (91.0 %) completed 4.5 years of follow-up. The overall incidence of febrile illness was 30 (LATAM, 26.0; APAC, 35.1) cases per 100 person-years. The rate samples collected during the acute phase was 98.1 %. The overall rate of samples collected after 5 days of fever onset (missed/out-of-window) was 6 % (LATAM, 10 %; APAC, 2 %). A trend toward reduced missed/out-of-window samples was observed after implementing measures, such as transportation, engagement, and healthcare aid tailored per study site in 2017, which appeared to increase during the COVID-19 pandemic. Conclusion: The design of the febrile surveillance protocol ensured high compliance in the trial. Maintaining engagement and access to healthcare beyond the protocol was important in improving febrile case evaluation ≤5 days of fever onset. |
| format | Article |
| id | doaj-art-57d58a50278f492aacda93a508aecfae |
| institution | OA Journals |
| issn | 1873-0442 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
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| series | Travel Medicine and Infectious Disease |
| spelling | doaj-art-57d58a50278f492aacda93a508aecfae2025-08-20T01:49:07ZengElsevierTravel Medicine and Infectious Disease1873-04422025-05-016510284010.1016/j.tmaid.2025.102840Operational challenges and lessons learned from conducting febrile surveillance in a long-term randomized dengue vaccine trial in Latin America and Asia-PacificHarald Pfaar0Eduardo López-Medina1Ian Escudero2Yanee Hutagalung3Nicholas Roubinis4Seloni Thakrar5Charissa Fay Corazon Borja-Tabora6Vianney Tricou7Suely Tuboi8Takeda Pharmaceuticals International AG, Zurich, SwitzerlandCentro de Estudios en Infectología Pediatrica CEIP, Department of Pediatrics, Universidad Del Valle, Clínica Imbanaco, Grupo Quironsalud, Cali, ColombiaTakeda Vaccines Inc., Cambridge, MA, USATakeda Pharmaceuticals (Asia Pacific) Pte. Ltd, SingaporeTakeda Pharmaceuticals International AG, Zurich, SwitzerlandTakeda Pharmaceuticals International AG, Zurich, SwitzerlandResearch Institute for Tropical Medicine, Filinvest Corporate City, Alabang, Muntinlupa, PhilippinesTakeda Pharmaceuticals International AG, Zurich, SwitzerlandTakeda Pharmaceuticals Brazil, São Paulo, Brazil; Corresponding author. Av. das Nações Unidas, 14.401 - Torre Jequitibá - 11° e 12° andares, São Paulo, SP, 04794-000, Brazil.Background: In trials, dengue vaccine efficacy evaluation relies on participants presenting with febrile illness/clinically suspected dengue contacting the study site for sample collection and clinical assessment within a short timeframe. Here, we present key considerations to maintain high compliance with the febrile surveillance procedures in a trial that assessed TAK-003 efficacy. Methods: DEN-301 (NCT02747927) is a randomized phase 3 trial in children/adolescents from eight dengue-endemic countries in Latin America (LATAM) and Asia-Pacific (APAC). Febrile surveillance consisted of weekly contact with the participant to identify cases of fever (≥38 °C; two of three consecutive days). Blood samples were collected for molecular testing, preferably ≤5 days of fever onset, together with thorough clinical assessment by the investigators. The data are presented descriptively. Results: Of the 20,071 (LATAM, 11,080; APAC, 8991) participants who received TAK-003/placebo, 18,260 (91.0 %) completed 4.5 years of follow-up. The overall incidence of febrile illness was 30 (LATAM, 26.0; APAC, 35.1) cases per 100 person-years. The rate samples collected during the acute phase was 98.1 %. The overall rate of samples collected after 5 days of fever onset (missed/out-of-window) was 6 % (LATAM, 10 %; APAC, 2 %). A trend toward reduced missed/out-of-window samples was observed after implementing measures, such as transportation, engagement, and healthcare aid tailored per study site in 2017, which appeared to increase during the COVID-19 pandemic. Conclusion: The design of the febrile surveillance protocol ensured high compliance in the trial. Maintaining engagement and access to healthcare beyond the protocol was important in improving febrile case evaluation ≤5 days of fever onset.http://www.sciencedirect.com/science/article/pii/S1477893925000468DengueVaccineFebrile surveillanceOperational aspectsChildrenAdolescents |
| spellingShingle | Harald Pfaar Eduardo López-Medina Ian Escudero Yanee Hutagalung Nicholas Roubinis Seloni Thakrar Charissa Fay Corazon Borja-Tabora Vianney Tricou Suely Tuboi Operational challenges and lessons learned from conducting febrile surveillance in a long-term randomized dengue vaccine trial in Latin America and Asia-Pacific Travel Medicine and Infectious Disease Dengue Vaccine Febrile surveillance Operational aspects Children Adolescents |
| title | Operational challenges and lessons learned from conducting febrile surveillance in a long-term randomized dengue vaccine trial in Latin America and Asia-Pacific |
| title_full | Operational challenges and lessons learned from conducting febrile surveillance in a long-term randomized dengue vaccine trial in Latin America and Asia-Pacific |
| title_fullStr | Operational challenges and lessons learned from conducting febrile surveillance in a long-term randomized dengue vaccine trial in Latin America and Asia-Pacific |
| title_full_unstemmed | Operational challenges and lessons learned from conducting febrile surveillance in a long-term randomized dengue vaccine trial in Latin America and Asia-Pacific |
| title_short | Operational challenges and lessons learned from conducting febrile surveillance in a long-term randomized dengue vaccine trial in Latin America and Asia-Pacific |
| title_sort | operational challenges and lessons learned from conducting febrile surveillance in a long term randomized dengue vaccine trial in latin america and asia pacific |
| topic | Dengue Vaccine Febrile surveillance Operational aspects Children Adolescents |
| url | http://www.sciencedirect.com/science/article/pii/S1477893925000468 |
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