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Letter in response to “Utilities and Limitations of the World Health Organization 2009 Warning Signs for Adult Dengue Severity“

Posted by OlafHorstick on 03 Jul 2013 at 07:04 GMT

Letter in response to "Utilities and Limitations of the World Health Organization 2009 Warning Signs for Adult Dengue Severity"
Tun-Linn Thein, Victor C. Gan, David C. Lye, Chee-Fu Yung, Yee-Sin Leo
PLOS NTD 17 January 2013

Horstick O1, Jaenisch T2, Kroeger A3, Lum L4, Martinez E5

1 – Institute of Public Health, University of Heidelberg, Germany
2 – Department of Tropical Medicine, University of Heidelberg, Germany
3 – Special Programme for Research and Training in Tropical Diseases WHO/TDR, Geneva, Switzerland
4 – Department of Child Health, University of Malaya, Kuala Lumpur, Malaysia
5 – Instituto de Medicina Tropical Pedro Kuori, La Habana, Cuba

Tun-Linn et al. reported a retrospective study of the warning signs - as described in the new dengue case classification (WHO 2009) - in relation to Dengue Haemorrhagic Fever (DHF) and Severe Dengue (SD).

The authors of this response welcome the study of the relationship of warning signs and severe dengue. This can potentially help to triage and follow up cases of dengue, depending on the severity of the case, resulting either in a higher frequency of observation and/or hospitalisation. This should translate into improved clinical management and a lower mortality rate of dengue.

However, we wish to caution that warning signs have been in use in clinical practice for a long time, despite the knowledge that their sensitivities and specificities are far from perfect. Warning signs have been used by clinicians as an additional tool and their power has been described using a framework of risk increase in those where the warning sign is present over those where it is not present.

The warning signs currently proposed are broad clinical signs that can occur in many diseases. Their usefulness in dengue has mostly relied on expert opinion – with the exception of few studies that have tried to provide empirical evidence for their usefulness. Hence, a prospective study design is of paramount importance to provide high quality data.

A major weakness of the results presented by Tun-Linn et al is the retrospective nature of their data. Could the authors assure that a given warning sign was truly absent as opposed to being just not recorded?

In the DENCO study prospective empirical evidence for the usefulness of warning signs was generated (Alexander 2011) - however, as this was a secondary objective of the study, the evidence generated should be regarded as preliminary findings in relation to warning signs.
Based on the fact that there is a need for better evidence regarding warning signs large prospective studies are currently ongoing in collaboration with WHO/TDR. These studies are in line with the attempt to develop the new dengue case classification, to attain the highest level of evidence and not relying on expert opinion only (Bandhyopadhay 2005, Horstick 2012).

Additionally - and to be fair to the criticism against the use of warning signs - it has to be pointed out that the study is based on the dataset of a single specialised centre, with presumingly a higher proportion of more severe cases of dengue. Warning signs have their value especially in the context of primary care, where most of the triage work occurs and studies should include cases in primary care.

Some of our points have been listed as limitations by Tun-Linn et al. However, we wish to reiterate that studies about warning signs need to be prospective and should include primary care, in order to address the question of how warning signs can be used in the context of severe dengue, the very question Tun-Linn et al. intended to tackle.

Alexander N, Balmaseda A, Castelobranco I, Dimaano E, Hien TT, Hung NT, et al. Evidence for a revised dengue case classification: a multi-centre prospective study across Southeast Asia and Latin America. Trop Med Int Health. 2011;16(8):936–48

Bandyopadhyay S, Lum LC, Kroeger A, (2006) Classifying dengue: a review of the difficulties in using the WHO case classification for dengue hemorrhagic fever. Trop Med Int Health 11: 1238–1255

Horstick O, Farrar J, Lum L, Martinez E, San Martin JL, Ehrenberg J, Velayudhan R, Kroeger A (2012) Reviewing the development, evidence base and application of the revised dengue case classification, Pathogens and Global Health, Volume 106, Number 2, May 2012 , pp. 94-101(8)
World Health Organization (2009) Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. Geneva: World Health Organization ISBN 978 92 4 154787 1

No competing interests declared.