Peer review process
Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, public reviews, and a response from the authors (if available).
Read more about eLife’s peer review process.Editors
- Reviewing EditorMauro TeixeiraUniversidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Senior EditorDiane HarperUniversity of Michiganâ€Ann Arbor", Ann Arbor, United States of America
Reviewer #1 (Public Review):
Summary:
This manuscript by Vuong and colleagues reports a study that pooled data from 3 separate longitudinal studies that collectively spanned an observation period of over 15 years. The authors examined for correlation between viraemia measured at various days from illness onset with thrombocytopaenia and severe dengue, according to the WHO 2009 classification scheme. The motivation for this study is both to support the use of viraemia measurement as a prognostic indicator of dengue and also when an antiviral drug becomes licensed for use, to guide the selection of patients for antiviral therapy. They found that the four DENVs show differences in peak and duration of viraemia and that viraemia levels before day 5 but not those after from illness onset correlated with platelet count and plasma leakage at day 7 onwards. They concluded that the viraemia kinetics call for early measurement of viraemia levels in the early febrile phase of illness.
Strengths:
This is a unique study due to the large sample size and longitudinal viraemia measurements in the study subjects. The data addresses a gap in information in the literature, where although it has been widely indicated that viraemia levels are useful when collected early in the course of illness, this is the first time anyone has systematically examined this notion.
Weaknesses:
The study only analysed data from dengue patients in Vietnam. Moreover, the majority of these patients had DENV-1 infection; few had DENV-4 infection. The data could thus be skewed by the imbalance in the prevalence of the different types of DENV during the period of observation. The use of patient-reported time of symptom onset as a reference point for viraemia measurement is pragmatic although there is subjectivity and thus noise in the data.
Reviewer #2 (Public Review):
Summary:
This manuscript highlights very important findings in the field, especially in designing clinical trials for the evaluation of antivirals.
Strengths:
The study shows significant differences between the kinetics of viral loads between serotypes, which is very interesting and should be taken into account when designing trials for antivirals.
Weaknesses:
The kinetics of the viral loads based on disease severity throughout the illness are not described, and it would be important if this could be analyzed.
