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NTDs and evidence: the case of dengue. A letter in response to “Has the NTD Community Neglected Evidence-Based Policy?” by Sukrti Nagpal, David Sinclair and Paul Garner, PLOS NTD, July 2013, Volume 7, Issue 7

Posted by OlafHorstick on 11 Mar 2014 at 21:41 GMT

NTDs and evidence: the case of dengue. A letter in response to “Has the NTD Community Neglected Evidence-Based Policy?” by Sukrti Nagpal, David Sinclair and Paul Garner, PLOS NTD, July 2013, Volume 7, Issue 7

Olaf Horstick(1) and Silvia Runge Ranzinger(2,3)

1 Institute of Public Health, University of Heidelberg, Germany
2 Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland
3 Consultant in Public Health, Ludwigsburg, Germany

* Corresponding author: Dr Olaf Horstick,

The contribution of Nagpal et al. is very much welcome in times that funding for Neglected Tropical Diseases (NTDs) continues to be difficult, representing only a fraction of spending in other health areas (1). To be fair, there are lately positive trends for research and development (R&D) in NTDs, as described by G-Finder in 2013 (2), with an increase in funding: “....This is a positive change compared to recent years, as global investment in neglected disease R&D had been declining since 2009”. However, the question remains important what to fund, both in research and in control programmes for NTDs, especially considering that these “diseases of poverty” occur mostly in extremely deprived populations - every money allocation needs to be well spent.

In our brief response we would like to give the example for dengue, since many points raised by Nagpal et al. are equally present in the control of dengue, but in dengue there are also advances, especially related to the documentation of efficacy and community effectiveness of interventions. To conduct the argument we 1) briefly explain the history of key WHO documents on dengue and 2) how these relate to the global efforts to work on improved summary evidence, linking research and practice for dengue and how 3) these efforts might lead to a new approach for dengue control, especially in the context of primary prevention of dengue, currently only possible through vector control.

History of key WHO documents on dengue
In 2006 WHO convened a group of experts to help prioritising future research areas in dengue (Scientific Working Group on dengue (3)), one of these areas is health policy research: “tools for rational decision-making and adequate prioritisation of dengue” were asked for. In a further development, during the development of the new WHO dengue guidelines (4), WHO developed at the same time higher standards for guidelines, with the establishment of the “guidelines review committee” (5). Following the WHO handbook for development of guidelines (6), specifically high level evidence is needed, including systematic reviews.

Global efforts for improved summary evidence
Prior to the development of the new WHO dengue guidelines, only very few systematic reviews existed, including two studies in the Cochrane library (7,8). - one on dengue vaccines: even today there are no vaccines available for public health use; and one on corticosteroid use: a treatment that in practice is not used or recommended for dengue.
During the development of the new WHO dengue guidelines (4) - and answering to the newly defined needs of high level evidence for developing guidelines - several systematic reviews were published or were being published (9,10,11). However many key questions in dengue have not been addressed. These include clinical interventions, interventions in surveillance and outbreak response, but especially vector control, the only currently available intervention to reduce dengue morbidity. A subsequent systematic review on vector control service delivery (12) highlighted many shortcomings how vector control is being delivered globally. A meta-analysis on all existing vector control interventions was also published (13), however there was a concern that many studies with valuable information were excluded in this study, in order to reach the comparability needed for a meta-analysis. Also further questions around secondary and tertiary prevention in dengue emerged.
In this context, the authors developed a plan to systematically address dengue as a health problem with systematic reviews, along a 1) Strategic level, 2) Interventions for a service orientated purpose and 3) Single interventions, further stratified by primary, secondary and tertiary prevention levels - in part in collaboration with one of the larger international dengue research collaborations (IDAMS):

A new approach for dengue control
With the emerging evidence from the systematic reviews - at this stage partly published, partly submitted and partly under development - and following the ideas proposed by Nagpal et al., more evidence-informed decision-making for dengue control can be made in the future. For the strategic level, there are now systematic reviews available on the organisation of vector control services (12), community delivery of interventions (10) and on the costs of outbreaks (14). For the interventions focusing on a particular service delivery, for surveillance there is existing work on indicators for outbreak prediction (11) - soon to be updated - and work on outbreak response (15), further work will be available on the use of the 2009 WHO dengue case classification (16), on models for estimates of dengue infections, on entomological methods and also on entomological surveillance; for single interventions, on the primary prevention level, there is existing work on peridomestic space spraying (17) and on Bacillus thuringensis israelensis (18). Further work will be soon available on the use of Temephos, Copepods and larvivorous fish. For secondary and tertiary prevention, the use of intravenous rehydration fluids has been analysed (19), further work will soon be published on dengue and co-morbidities. Work is also under way on the use of NS1 diagnostics.
One of the key arguments by Nagpar et al. were that difficulties emerge, when evidence derived from studies can not recommend a particular intervention, but there are experts recommending these interventions nevertheless. From our preliminary analysis of the work on vector control, we now hypothesize that this may be the case for vector control, especially since very limited evidence exists to link vector control with a reduction of dengue transmission. Partly the reason is that the studies to show this link are technically difficult, but also, we now think that efficacy and especially community-effectiveness of vector control interventions are not very good, especially of the implementation is not to high standards. Quality control of implementation combined with integration of communities to reach a multiplier function in the delivery of interventions, may play a crucial role. A completely new set of recommendations may emerge from this work, similarly as Nagpar et al. said: “the continued delivery of the intervention may waste public resources, or fail to bring about all of the promised benefits”.

Following the article of Nagpar et al, we are convinced that for dengue - yet another NTD - many questions have been addressed with systematic reviews by our very systematic approach. The body of high level evidence in dengue is clearly growing to allow for improved evidence-informed decision-making.
As a word of caution however, this effort to link research and practice needs uptake of the summarised knowledge and its best-practice recommendations by the programme planners globally, combined with processes to disseminate the knowledge.

Authorship: OH and SRR devised the idea for this review and were both involved in the first and the final drafting of this article.

Funding: No funds were received for this review.

Conflicts of Interests: None declared

Ethics: Not required

1 Smith J, Taylor EM (2013). MDGs and NTDs: Reshaping the Global Health Agenda. PLoS Negl Trop Dis 7(12)
http://www.ploscollection... (Accessed 11.02.14)

2 G-Finder (2013). Neglected Disease research and development: the public divide. Policy Cures, London, United Kingdom.
http://www.policycures.or... (Accessed 11.02.14)

3 WHO/TDR (2006). Report on Dengue, Scientific Working Group, WHO, Geneva, 01-05 October 2006. (Accessed 11.02.14)

4 WHO/TDR (2009). Dengue, Prevention, Treatment and Control, New Edition, WHO 2009, ISBN 978 92 4 154787 1. (Accessed 11.02.14)

5 WHO guidelines review committee (2014). (Accessed 11.02.14)

6 WHO (2012). WHO Handbook for guidelines development.
(Accessed 11.02.14)

7 Schiøler KL, McCarty CW (2003). The Cochrane library: Vaccines for preventing dengue infection, DOI: 10.1002/14651858.CD004613

8 Panpanich R, Sornchai P, Kanjanaratanakorn K (2006). The Cochrane library: Corticosteroids for treating dengue shock syndrome (Review).
http://www.thecochranelib... (Accessed 11.02.14)

9 Bandyopadhyay S, Lum LC, Kroeger A (2006). Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever. Trop Med Int Health (2006) 11: 1

10 Heintze C, Velasco Garrido M (2007). What do community-based dengue control programmes achieve? A systematic review of published evaluations. Trans R Soc Trop Med Hyg. 2007 Apr;101(4):317-25

11 Runge Ranzinger S, Horstick O, Marx M and Kroeger A (2008). Systematic Review: What does dengue disease surveillance contribute to predicting and detecting outbreaks and describing trends?, TMIH, Volume 13 No 8 PP 1022–1041 August 2008

12 Horstick O, Runge Ranzinger S, Nathan MB, Kroeger A (2010). Dengue vector-control services: how do they work? A systematic literature review and country case studies, Transactions of the Royal Society of Tropical Medicine and Hygiene 104 (2010) 379–386

13 Erlanger TE, Keiser J, Utzinger J (2008). Effect of dengue vector control interventions on entomological parameters in developing countries: a systematic review and meta-analysis, Medical and Veterinary Entomology (2008) 22, 203–221

14 Stahl HC, Butenschoen VM, Tran HT, Gozzer E, Skewes R, Mahendradhata Y, Runge-Ranzinger R, Kroeger A, Farlow A (2013). Cost of dengue outbreaks: literature review and country case studies. BioMedCentral November 2013,
http://www.biomedcentral.... (Accessed 11.02.14)

15 Pilger D, De Maesschalck M, Horstick O, San Martin JL (2010). Dengue outbreak response: documented effective interventions and evidence gaps. TropIKA Reviews, (Accessed 11.02.14)

16 Horstick O, Martinez E, Jaenisch T, Kroeger A, Runge Ranzinger S (2014). Comparing the usefulness of the old and new WHO dengue case classification: A systematic literature review (Accepted AJTMH 2014)

17 Ekpereonne E, Lenhart A, Smith L and Horstick O (2010). Effectiveness of peridomestic space spraying with insecticide on dengue transmission; systematic review, TMIH, Volume 15 No 5 PP 619–631 May 2010

18 Boyce R, Lenhart A, Velayudhan R, Horstick O (2013). Boyce R, Lenhart A, Kroeger A, Velayudhan R, Horstick O Bacillus thuringiensis israelensis (Bti) for the control of dengue vectors: A systematic review TMIH Volume 18, Issue 5, pp 564–577, May 2013

19 Uzman H, Safitri I, Lum L, Martinez E, Kroeger A, Horstick O (2012). The effectiveness of intravenous rehydration to prevent death from severe dengue Dengue Bulletin 36, 2012, pp 149 - 165 (Accessed 11.02.14)

No competing interests declared.