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Thanks for Nguyen Tien Huy et al's comments.
Actually, our study population is during 2000-2012, not 2015. Taiwan National Health Insurance Research Database only released data before 2013. Therefore, we can not identify the stroke outcomes in 2014-2015 outbreaks.
The evidence derived from a cohort study is generally of lower methodological quality than that from a randomized controlled trial, because a cohort study is subject to many biases and unmeasured confounders. In spite of our efforts to control biases and adjust confounding factors, this observational cohort study could only find the association instead of causality between dengue and strokes.
We agree that further studies are needed to explore the cerebrovascular sequelae in dengue patients and investigate the possible pathogenesis of dengue-related stroke.Competing Interests: None declared. - Page navigation anchor for RE: Higher incidence of stroke in patients with dengue fever: Spurious association or causal link?RE: Higher incidence of stroke in patients with dengue fever: Spurious association or causal link?
A recently published population-based cohort study by Li and colleagues (1) suggests that stroke patients in Taiwan were 2.49 times more likely to have been diagnosed with dengue infection in the preceding two months relative to paired controls. Although rare, dengue-associated stroke does meet the criteria for severe dengue diagnosis based on guidelines from the World Health Organization (2). Li and colleagues report an overall increase in the incidence of stroke attributable to dengue by 1.61 per 1000 person-years during 2015. If these findings are extended to all 43,419 cases of dengue across Taiwan in 2015 (3), then 70 cases of stroke would have occurred due to dengue infection. This is alarming, particularly considering that there are 96 million cases of symptomatic dengue each year worldwide (4). Have the authors identified a spurious association, or is there a genuine causal link between dengue and stroke? Co-morbidity of dengue and hemorrhagic stroke have been reported in 0.26% of cases (3 of 1,148) in India (5), and 0.06% of cases (1 of 1,585) in Brazil (6).
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Rigorous research is urgently needed to characterise the sequelae of conditions that may arise from dengue infection, including the severity and duration of underlying disease such as diabetes mellitus and hypertension, conditions that may modify the effect of dengue on the risk of stroke. If the effect of dengue on stroke is acute rather than chronic, then there must be a pathophysiologic mechanis...Competing Interests: None declared. - Page navigation anchor for Author's replyAuthor's reply
Thanks for Ibrahim Radwan's interest and question. We've checked the reference 1-4, which used the data sources from Taiwan Centers for Disease Control (Taiwan CDC), in contrast to our study using Taiwan National Health Insurance Research Database (NHIRD).
The reason for less dengue patients during 2000-2012 in our study, may be that our study population were hospital inpatients, while the dengue patients collected in Taiwan CDC included those without hospitalization. As reported in Luh's study4, hospitalization only accounts for 86% of direct costs associated with dengue patients in Taiwan; some dengue patients may be only treat in outpatients or emergency.
Besides, the reason for more cases of dengue hemorrhagic fever (DHF) in our study is that, NHIRD included not only "indigenous", but also "imported" cases.
Taiwan CDC only reported indigenous DHF cases, without details in imported dengue cases.
As shown in Wang's study3 (Table 1), there were 1769 imported dengue cases during 2000-2012, such as travelers or immigrant workers. Taiwan CDC did not report details about DHF in these 1769 cases.
However, our study population would include them if they had hospitalization records.Hope this could answer your questions.
Reference
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1. Hsu H-Y, Lai S-K, Kuo C-H, Wu C-W, Liu D-P. An epidemiological analysis of dengue hemorrhagic fever cases in Taiwan from 2003 to 2011. Epidemiology Bulletin 20...Competing Interests: None declared. - Page navigation anchor for RE: Incidence of stroke in dengue fever in Taiwan: is it a population-based data?RE: Incidence of stroke in dengue fever in Taiwan: is it a population-based data?
Sir, I have read the interesting article of Dr. Li and co-authors, entitled “Risk of stroke in patients with dengue fever: a population-based cohort study” on the incidence of stroke in dengue fever patients.1 The study, based on population data, stated a significant association between risk of stroke and dengue fever. It is controversial with no presence of a reasonable pathophysiological mechanism of stroke in dengue. The study stated using a data from the Taiwan National health Insurance Research Database (NHIRD) to conduct a population-based study, patients with newly diagnosed with dengue fever, selected from 2000 to 2012, is about 14552 patients. Then, with excluding 765 records of patients with stroke before index date, missing basic data and recurrent, the dengue group contained 13787 patients, including 12477 (90.5%) of dengue fever (DF) and 1310 (9.5%) of dengue hemorrhagic fever (DHF).
Based on published epidemiological studies2-5, distribution of recorded indigenous cases of DF and DHF during 2000-2012 was shown in (Table 1). About 15347 indigenous dengue cases were recorded during 2000-2012 and including 14968 (98%) as DF and 379 (2%) as DHF. About 72.2% of DHF cases were recorded during the dengue outbreak in 2002 and from 2003 to 2011, there were only 93 cases of DHF. This in contrast with characteristics in Lin et al.1 which demonstrated high in DHF patients, compared to other studies records, is about 10% of dengue patients.Table 1 Distribu...
Show MoreCompeting Interests: None declared. - Page navigation anchor for Author's replyAuthor's reply
We thank Dr Joob and Wiwanitkit for sharing their experience regarding our recent study.[1] We agree that stroke is an uncommon neurological complication in dengue patients. As shown in our study, the overall incidence rate of stroke in our dengue cohort was 5.33 per 1,000 person-years, with adjusted HR of 1.16 (95% CI 1.01-1.32) compared to the control cohort. Interestingly, we found the stroke risk in dengue patients was time-dependent, as high as 25.52 per 1,000 person-years (adjusted HR 2.49, 95% CI 1.48-4.18) in the first two month. The increased risk of stroke in dengue patients was not only for hemorrhagic stroke, but also for ischemic stroke. This may be due to the universal screening and surveillance program of dengue established by Taiwan CDC, and the easy accessibility of medical care in Taiwan, improving the early detection of ischemic stroke in dengue patients. In the review from Carod-Artal et al.,[2] they also assumed that ischemic strokes related to dengue might be underestimated in dengue-endemic countries. The concern of the association between ischemic stroke and dengue is critical for clinical practice in dengue-endemic area. Because the treatments of acute ischemic stroke include administration of thrombolytic agent and intraarterial thrombectomy. Using these treatments on under-diagnosed dengue patients will increase the risk of intracranial hemorrhage and lead to deadly outcome.
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To our best knowledge, this is the first study reporting epide...Competing Interests: None declared. - Page navigation anchor for RE: Risk of stroke in patients with dengue fever: a population-based cohort study - is there a real increased risk?RE: Risk of stroke in patients with dengue fever: a population-based cohort study - is there a real increased risk?
We read this publication on "Risk of stroke in patients with dengue fever: a population-based cohort study" with a great interest [1]. Li et al. concluded that "In this population-based study, the presence of dengue was associated with an increased risk of stroke. The effect of dengue on stroke may be acute rather than chronic [1]." We would like to share ideas and experience from our country in Indochina where there is an extremely high prevalence of dengue. The neurological complication due to dengue is a possible but stroke is extremely uncommon [2]. in the present study, it is unlikely to control the other confounding factors that might result in the occurrence of stroke. If there is an actual increased risk, there should be any possible pathomechanism. In fact, the main problem in dengue is the hemostatic disorder and the only possible mechanism is hemorrhage. Nevertheless, the hemorrhagic stroke is rare and a good clinical supportive care due acute dengue infection is usually sufficient to prevent dengue complication [3].
Conflict of interest
NoneReferences
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1. Li HM, Huang YK, Su YC, Kao CH. Risk of stroke in patients with dengue fever: a population-based cohort study. CMAJ. 2018 Mar 12;190(10):E285-E290.
2. Wiwanitkit S, Wiwanitkit V. Neurological complications in dengue infection. Arq Neuropsiquiatr. 2014 Mar;72(3):259.
3.Wiwanitkit V. Intracranial Hemorrhage in Dengue: Where Is It? Asian J Neurosurg. 2...Competing Interests: None declared.