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Corticosteroids for treating dengue shock syndrome

  1. Ratana Panpanich1,*,
  2. P Sornchai2,
  3. Kittika Kanjanaratanakorn3

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 17 FEB 2010

Assessed as up-to-date: 8 JAN 2006

DOI: 10.1002/14651858.CD003488.pub2

Database Title

Additional Information

How to Cite

Panpanich R, Sornchai P, Kanjanaratanakorn K. Corticosteroids for treating dengue shock syndrome. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD003488. DOI: 10.1002/14651858.CD003488.pub2.

Author Information

  1. 1

    Faculty of Medicine, Community Medicine, Chiang Mai, North, Thailand

  2. 2

    Nakornping Hospital, Chiang Mai, Thailand

  3. 3

    Faculty of Medicine,Chiang Mai University, Clinical Epidemiology Unit, Chiang Mai, Thailand

*Ratana Panpanich, Community Medicine, Faculty of Medicine, Chiang Mai University, 110 Intawaroros, Chiang Mai, North, 50200, Thailand. rpanpani@mail.med.cmu.ac.th.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 17 FEB 2010

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Definition

Dengue virus is an arbovirus transmitted to humans by two species of mosquito, Aedes aegypti and A. albopictus. The four serotypes of dengue virus can cause a wide range of symptoms from mild febrile illness to severe haemorrhagic fever, which leads to dengue shock syndrome. Dengue haemorrhagic fever is said to be present when patients have high fever for two to seven days, bleeding, enlargement of the liver, and insufficient circulation (Nimmanitya 1993). Bleeding usually occurs and frequently presents as tiny, scattered, red spots in the skin (petechiae). Bleeding from the nose, gums, and gastrointestinal tract is less common but may be severe. There are four grades dengue haemorrhagic fever according to the level of shock or bleeding: grades I and II are non-shock dengue haemorrhagic fever, and grades III and IV are cases with shock (dengue shock syndrome) (WHO 1997).

 

Epidemiology

Dengue haemorrhagic fever was first recognized in South-East Asia in the 1950s when outbreaks occurred in Philippines, Thailand, and Vietnam. The incidence of dengue haemorrhagic fever has increased in several countries in Asia and is one of the leading causes of death in children (Thongcharoen 1993). It is currently estimated that the majority of the 100 million cases of dengue infection that occur annually are in South-East Asia (Kautner 1997). Dengue haemorrhagic fever is also endemic in some parts of the Americas. Twenty-five countries in the Americas reported 42,246 cases of dengue haemorrhagic fever and 582 deaths between 1981 and 1996 (Pinheiro 1997), and an epidemic occurred in Cuba in 1981. There are increasing numbers of imported cases of dengue infection among travellers returning from these endemic areas (Kautner 1997).

 

Pathogenesis

It is unclear how dengue infection causes bleeding and shock. Immune responses seem to play an important role in causing illness. Infection with one of the four serotypes of dengue virus provides lifelong immunity to that serotype. Secondary infection with another serotype of dengue virus can form a 'virus-antibody complex' by combining with existing antibody from previous dengue infection. The virus-antibody complex promotes the growth of the virus in mononuclear cells and activates the complement system (Halstead 1993). In another hypothesis, genetic changes in the virus genome increase viral replication, virulence, and epidemic potential of the dengue virus (Gubler 1998). Capillary damage and increased permeability of vessel walls cause plasma to flow into extravascular spaces and increase the blood concentration. A depletion of plasma volume can cause low blood pressure and lead to shock in severe cases. Bleeding in dengue haemorrhagic fever is related to platelet depletion (thrombocytopenia, ≤ 100,000 platelets/mm3), which results from the depression of megakaryocyte function and increased destruction of mature platelets. It may also be involved with microvascular injury, platelet dysfunction, and clotting defect in blood vessels (disseminated intravascular coagulation) (Nelson 1964; Mitrakul 1979). Complications such as encephalopathy, hepatic failure, and renal failure can occur but are unusual.

 

Management

The standard treatment of dengue shock syndrome is to immediately administer intravenous fluids to expand plasma volume. People are at particular risk of circulatory problems when their fever resolves. Plasma leakage is thought to be self limiting and rarely lasts longer than 48 hours, so clinicians prevent shock by replacing the plasma volume as soon as the haematocrit concentration starts to rise (Nimmanitya 1993). Clinicians give blood if patients are bleeding. There are no drugs available specifically for the treatment of dengue haemorrhagic fever. Although carbazochrome sodium sulfonate (AC-17) was tested in clinical trials because it is thought to be protective against vascular damage and decrease the severity of plasma leakage, the authors of one study concluded no benefit was shown (Tassniyom 1997).

Corticosteroids are potent anti-inflammatory agents that have a wide range of effects on immunological processes and have found use in a broad spectrum of diseases (Kehrl 1983). The use of corticosteroids in the management of dengue haemorrhagic fever and dengue shock syndrome is under debate. The World Health Organization does not mention corticosteroids in the treatment guidelines for dengue shock syndrome (WHO 1997). Observational studies in Thailand have shown a marked decline in case-mortality rate without any use of corticosteroids; this was attributed to both close observation of the patients for signs of shock during the critical period and early replacement of plasma loss (Cohen 1964; Nimmanitya 1978). Corticosteroids are used in some countries, particularly those in South-East Asia for managing dengue shock syndrome. They are thought to be effective for stabilizing capillary permeability and have been used in addition to fluid replacement (Sumarmo 1987). This systematic review examines the best available evidence on the effects of corticosteroids on death in dengue shock syndrome.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

To compare corticosteroids with placebo or no corticosteroids for treating dengue shock syndrome.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomized and quasi-randomized controlled trials.

 

Types of participants

People diagnosed with dengue shock syndrome, as defined by the trial authors.

 

Types of interventions

 

Intervention

Corticosteroids (methylprednisolone, hydrocortisone, dexamethasone).

 

Control

Placebo or no corticosteroids.

 

Types of outcome measures

 

Primary

Death.

 

Secondary

  • Time to regain normal blood pressure.
  • Intravenous fluid requirement during the period of shock.
  • Blood transfusion.
  • Severe complications, including pulmonary oedema, renal failure, hepatic failure, pulmonary haemorrhage and convulsion.
  • Days in hospital.
  • Adverse events.

 

Search methods for identification of studies

We attempted to identify all relevant trials regardless of language or publication status (published, unpublished, in press, and in progress).

 

Databases

We searched the following databases using the search terms and strategy described in Appendix 1: Cochrane Infectious Diseases Group Specialized Register (August 2009); Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library (2009, Issue 2); MEDLINE (1966 to August 2009); EMBASE (1974 to August 2009); and LILACS (1982 to August 2009).

 

Researchers

We contacted individual researchers working in the field for unpublished trials.

 

Reference lists

We also checked the reference lists of all studies identified by the above methods.

 

Data collection and analysis

 

Selection of studies

Two authors independently screened the results of the literature search for potentially relevant trials. We used an eligibility form to assess these trials for inclusion in the review; the reasons for excluding studies are in the 'Characteristics of excluded studies'.

 

Data extraction and management

We used data extraction forms to collect information on the participants, methods, interventions, and outcomes. The first two authors independently extracted data. Where there were differences, we referred to the original papers. We checked the data sources to avoid extracting data from multiple publications based on the same data set.

 

Assessment of risk of bias in included studies

Two authors independently assessed generation of allocation sequence and allocation concealment as adequate, inadequate, or unclear (Jüni 2001). We also described who was blinded, and assessed the inclusion of all randomized participants in the final analysis to be adequate if 90% or more.

 

Data synthesis

We used Review Manager 5 for data analysis. We combined dichotomous data using risk ratio (RR) and combined continuous data using mean difference (MD), both with 95% confidence intervals (CI).

We assessed heterogeneity by visually examining the forest plots and by using the chi-squared test for heterogeneity with a 10% level of statistical significance. The I2 statistic was also used to measure inconsistency results among trials (Higgins 2003). We intended to explore disease severity and corticosteroid dose and type as potential sources of heterogeneity, but there were too few trials.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

Four randomized controlled trials involving 284 participants met the inclusion criteria (see 'Characteristics of included studies') and four were excluded (see 'Characteristics of excluded studies').

 

Trial location and participants

Two trials were conducted in Thailand (Pongpanich 1973; Tassniyom 1993), one in Burma (now known as Myanmar) (Min 1975), and one in Indonesia (Sumarmo 1982). Participants were children aged less than 15 years with serologically confirmed dengue and shock.

 

Interventions

Three trials compared intravenous hydrocortisone hemisuccinate with no corticosteroids or placebo (Pongpanich 1973; Min 1975; Sumarmo 1982), and one compared methyl prednisolone with placebo (Tassniyom 1993).

 

Outcomes

All four trials reported on death (Pongpanich 1973; Min 1975; Sumarmo 1982; Tassniyom 1993), two reported the number needing a blood transfusion (Pongpanich 1973; Tassniyom 1993), and one reported the duration of hospitalization (Tassniyom 1993).

 

Risk of bias in included studies

Also see  Table 1 and the 'Characteristics of included studies'.

Generation of allocation sequence was adequate in one trial. No trials described allocation concealment, three trials used double blinding, and the same three trials were adequate for the number of randomized participants included in the analysis.

 

Effects of interventions

 

Death

Death was an outcome in all four trials, but only three reported deaths (Min 1975; Sumarmo 1982; Tassniyom 1993). Overall no benefit of corticosteroids was demonstrated, but the number of participants in the analysis was small (284 participants,  Analysis 1.1).

 

Blood transfusion

There was no statistically significant difference in the number of participants needing blood transfusion (89 participants, 2 trials, Analysis 1.2) (Pongpanich 1973; Tassniyom 1993).

 

Complications

Tassniyom 1993 reported no statistically significant difference between the corticosteroids and placebo for convulsions and pulmonary haemorrhage (63 participants,  Analysis 1.3).

 

Days in hospital

Tassniyom 1993 reported an average stay of 6.2 days in the placebo group and 7.3 days in the corticosteroid group (63 participants,  Analysis 1.4).

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Trials in people with a life-threatening illness are not easy to conduct, and the authors of these trials did their best to ensure an unbiased comparison. However, the trials were conducted some time ago and methods have become more advanced and more stringent. In the context of current standards, these trials have potential for bias, as allocation was not clearly concealed in any of them. Four trials were included in the review and the results showed no benefits of corticosteroids in reducing death in dengue shock syndrome.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

 

Implications for practice

There is insufficient evidence to justify the use of corticosteroids in managing dengue shock syndrome. They should not be used in dengue shock syndrome outside the context of carefully conducted randomized controlled trials.

 
Implications for research

Large, randomized controlled trials that carefully conceal allocation and measure death as an outcome are required. Types, dose, and duration of corticosteroids should also be studied.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Ratana Panpanich developed the protocol for this review during the Fellowship Programme organized in May and June 2001 by the Cochrane Infectious Diseases Group. The UK Department for International Development (DFID) supported this Fellowship through the Effective Health Care Alliance Programme at the Liverpool School of Tropical Medicine.

This document is an output from a project funded by the DFID for the benefit of developing countries. The views expressed are not necessarily those of DFID.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
Download statistical data

 
Comparison 1. Corticosteroids versus no corticosteroids or placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Death4284Risk Ratio (M-H, Fixed, 95% CI)0.68 [0.42, 1.11]
 2 Blood transfusion289Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.52, 2.24]
 3 Complications1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    3.1 Pulmonary haemorrhage
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    3.2 Convulsions
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 4 Days in hospital1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Appendix 1. Search methods: detailed search strategies

Search setCIDG SRaCENTRALMEDLINEbEMBASEbLILACSb
1adrenal cortex hormoneadrenal cortex hormoneexp DENGUEexp DENGUEdengue
2corticosteroidscorticosteroidsdenguedenguecorticosteroids
3hydrocortisonehydrocortisoneHEMORRAGIC FEVERHEMORRAGIC FEVERdexamethasone
4dexamethasonedexamethasonehemorrhagic feverhemorrhagic feverprednisolone
5methylprednisolonemethylprednisolone('break-bone fever').ti,ab('break-bone fever').ti,ab2 or 3 or 4
6prednisoloneprednisolone1 or 2 or 3 or 4 or 51 or 2 or 3 or 4 or 51 and 5
7hemorrhagic feverhemorrhagic feverADRENAL CORTEX HORMONESadrenal cortex hormones—
8dengue feverdengue fevercorticosteroidscorticosteroids—
9——steroid*steroid$—
10——cortisol*cortisol$—
11——HYDROCORTISONEHYDROCORTISONE—
12——hydrocortisonehydrocortisone—
13——DEXAMETHASONEDEXAMETHASONE—
14——dexamethasonedexamethasone—
15——METHYLPREDNISOLONEMETHYLPREDNISOLONE—
16——methylprednisolonemethylprednisolone—
17——PREDNISOLONEPREDNISOLONE—
18——prednisoloneprednisolone—
19——7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 187 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18—
20——6 and 196 and 19—
21——Limit 20 to humanLimit 20 to human—


aCochrane Infectious Diseases Group Specialized Register.
bSearch terms used in combination with the search strategy for retrieving trials developed by The Cochrane Collaboration (Higgins 2005; upper case: MeSH or EMTREE heading; lower case: free text term.

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Last assessed as up-to-date: 8 January 2006.

DateEventDescription
12 August 2009New search has been performedNew search conducted; no new trials for inclusion


 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Protocol first published: Issue 1, 2002
Review first published: Issue 3, 2006

DateEventDescription
19 September 2008AmendedConverted to new review format with minor editing.


 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

All authors contributed to the development of the review, extraction of the data, analysis, and interpretation of the results.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Internal sources

  • Faculty of Medicine, Chiang Mai University, Thailand.

 

External sources

  • Department for International Development, UK.

 

Differences between protocol and review

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

The intravenous fluid requirement during the period of shock and blood transfusion were added as secondary outcomes measures as they are important supportive treatments in both groups. The amounts of fluids and blood requirements should be compared if they reported.

References

References to studies included in this review

  1. Top of page
  2. Abstract摘要
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
Min 1975 {published data only}
  • Min M, U T, Aye M, Shwe TN, Swe T. Hydrocortisone in the management of dengue shock syndrome. Southeast Asian Journal of Tropical Medicine and Public Health 1975;6(4):573-9.
Pongpanich 1973 {published data only}
  • Pongpanich B, Bhanchet P, Phanichyakarn P, Valyasevi A. Studies on dengue hemorrhagic fever: An evaluation of steroids as a treatment. Journal of Medical Association of Thailand 1973;56(1):6-14.
Sumarmo 1982 {published data only}
  • Sumarmo, Talogo W, Asrin A, Isnuhandojo B, Sahudi A. Failure of hydrocortisone to affect outcome in dengue shock syndrome. Pediatrics 1982;69(1):45-9.
Tassniyom 1993 {published data only}
  • Tassniyom S, Vasanawathana S, Chirawathul A, Rojanasuphot S. Failure of high-dose methylpredisolon in established dengue shock syndrome: A placebo-controlled, double-blind study. Pediatrics 1993;92(1):111-5.

References to studies excluded from this review

  1. Top of page
  2. Abstract摘要
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
Futrakul 1981 {published data only}
  • Futrakul P, Vasanauthana S, Poshyachinda M, Mitrakul C, Cherdboonchart V, Kanthirat V. Pulse therapy in severe form of dengue shock syndrome. Journal of Medical Association of Thailand 1981;64(10):485-90.
Futrakul 1987 {published data only}
  • Futrakul P, Poshyachinda M, Mitrakul C, Kwakpetoon S, Unchumchoke P, Teranaparin C. Hemodynamic response to high-dose methyl prednisolone an mannitol in severe dengue-shock patients unresponsive to fluid replacement. Southeast Asian Journal of Tropical Medicine and Public Health 1987;18(3):373-9.
Sumarmo 1975 {published data only}
  • Widya MS, Martoatmodjo. Clinical observations on dengue shock syndrome (an evaluation of steroid treatment). Paediatrica Indonesiana 1975;15(5-6):151-60.
Sumarmo 1987 {published data only}
  • Sumarmo. The role of steroids in dengue shock syndrome. Southeast Asian Journal of Tropical Medicine and Public Health 1987;18(3):383-9.

Additional references

  1. Top of page
  2. Abstract摘要
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
Cohen 1964
Gubler 1998
Halstead 1993
  • Halstead SB. Pathophysiology and pathogenesis of dengue haemorrhagic fever. Monograph on dengue/dengue haemorrhagic fever. New Delhi: World Health Organization Regional Office for South-East Asia, 1993:80-103.
Higgins 2003
Higgins 2005
  • Higgins JPT, Green S, editors. Highly sensitive search strategies for identifying reports of randomized controlled trials in MEDLINE. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 updated May 2005; Appendix 5b. www.cochrane.org/resources/handbook/hbook.htm (accessed 9 January 2006).
Jüni 2001
Kautner 1997
Kehrl 1983
Mitrakul 1979
  • Mitrakul C. Bleeding diathesis in dengue haemorrhagic fever. Southeast Asian Journal of Tropical Medicine and Public Health 1979;10(3):434-7.
Nelson 1964
Nimmanitya 1978
  • Nimmanitya S. Management of dengue hemorrhagic fever. Asian Journal of Infectious Diseases 1978;2:67.
Nimmanitya 1993
  • Nimmanitya S. Clinical manifestations of dengue/dengue haemorrhagic fever. Monograph on dengue/dengue haemorrhagic fever. New Delhi: World Health Organization Regional Office for South-East Asia, 1993:48-54.
Pinheiro 1997
  • Pinheiro FP, Corber SJ. Global situation of dengue and dengue haemorrhagic fever, and its emergence in the Americas. World Health Statistics Quarterly 1997;50(3-4):161-9.
Review Manager 5
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Tassniyom 1997
  • Tassniyom S, Vasanawathana S, Dhiensiri T, Nisalak A, Chirawatkul A. Failure of carbazochrome sodium sulfonate (AC-17) to prevent dengue vascular permeability or shock: a randomized, controlled trial. Journal of Pediatrics 1997;131(4):525-8.
Thongcharoen 1993
  • Thongcharoen P, Jatanasen S. Epidemiology of dengue and dengue haemorrhagic fever. Monograph on dengue/dengue haemorrhagic fever. New Delhi: World Health Organization, 1993:1-8.
WHO 1997
  • World Health Organization. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd Edition. Geneva: World Health Organization, 1997.
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