DENGUE HEMORRHAGIC FEVER (DHF)

Introduction:

Recently, I lost my uncle all of a sudden after hearing from and about him doing well, and keeping himself active in various ways including biking in the evenings. Being away from the site of incidence, it was mind boggling to know about the sudden transformation of events resulting in his ultimate death. To give a brief summary of the events:

My uncle was 72 years old, who was active and healthy with not much prior health complications. All of a sudden, he reported of ill health, and was taken to the hospital, where he was diagnosed with fever. After being kept in the hospital for couple of days, he was discharged when the temperature went down. At the same time, my uncle was never back to normal. Moreover, he started analyzing how his health issues might be tied to family history, which brought down his health further. Finally, his health condition dropped further, and was re-admitted. During the 2nd time of admission, he was diagnosed with stroke and lower levels of platelets count. Though doctors tried platelet transfusion to increase the level of platelets, it did not help in anyway resulting in his death.

Note: There are certain variables/specifics missing in terms of medicine administered and all the symptoms observed, but knowing the sequence of the events and the condition of occurrence led me to come up with the following analysis –

What could it be?

The sequence of events namely, viral fever followed by stroke and coma, which happened to be due to intracranial hemorrhage followed by/along with (not sure when the reduced level was determined) reduced level of platelets (platelet counts in the order of 10-20000/mm^3 rather than > 100000),1-3 which is called thrombocytopenia. Further, this incident happened in a tropical region known for mosquitoes suggesting that this particular case could have been due to hemorrhagic fever coming out of dengue virus.  Moreover, though not certain of all the symptoms that were observed, there were certainly some symptoms that I was informed of namely, headache, muscle pain, loss of appetite, general ill feeling, which further supported dengue viral infection.

Dengue fever (DF) and complications: - CDC recommendation3

Classic dengue fever which tends to last for 3 – 14 days, and results in febrile seizures and dehydration with common symptoms such as headache, retro-orbital pain, myalgias, low WBC count to name a few.

Recommended Treatment involves –

a.     relieving symptoms of pain

b.     controlling fever

c.      avoiding aspirin and other non-steroidal anti-inflammatory medications due to the risk of increasing hemorrhage potential

d.     drinking plenty of fluids

When the standard DF transforms to Dengue hemorrhagic fever (DHF), the standard warnings include severe abdominal pain, vomiting, marked change in temperature, hemorrhagic manifestations and/or change in mental health.”

DHF is currently defined by the following WHO criteria:

a.     Fever or recent history of fever lasting 2 to 7 days

b.     Any hemorrhagic manifestations

c.      Thrombocytopenia (< 100000/mm^3 platelet counts)

d.     Evidence of increased vascular permeability

When patient meets any one of the four mentioned criteria combined with circulatory failure are considered to have Dengue Shock Syndrome (DSS). Fatality rate for DSS right now is around 10% or more, but can be restricted to 1% through early recognition and proper treatment.”1

DHF and neurological manifestations:1-3

Based on a recent literature work published in 2013, 

“Dengue with neurological manifestations have been found in 0-5 – 21% (depending on the clinical setting) of the patients admitted to the hospital. Moreover, dengue was identified in 4 – 47% of admissions with encephalitis in endemic areas.

Neurological complications include dengue encephalopathy (caused by metabolic disorders or hepatic failure), encephalitis (direct virus invasion), neuromuscular dysfunctions (transient muscle dysfunctions) and neuro-opthalmic involvement.”

What could have happened in my uncle’s case?

First of, until now and to my best knowledge, I doubt that he was diagnosed with Dengue fever, and was treated for common viral fever. Without proper early recognition, it makes me wonder whether he had taken (or was provided) sufficient level of fluids, adequate rest, and took antipyretics instead of non-steroidal/anti-inflammatory medications. Moreover, the fever transformed into hemorrhagic manifestations combined with drop in mental health in a week’s time suggesting that he was most probably moving towards the DSS phase. 

While discussing DHF, also called, Dengue Encephalopathy, “it is important to understand the mechanism of action – DHF appears to involve CNS causing onset of hyperpyrexia, non-transient alteration of consciousness, headache, vomiting, but usually normal cerebrospinal fluid. At this point in time, there is limited information available other than the fact that the main pathology found in such cases being leakage of plasma into serous spaces, and abnormal hemostasis causing hypovolemic shock, hemorrhage in many organs of the body. Liver failure appears to be the primary factor causing brain pathology.”

Is there anything that could have been done post-DHF/DSS?

Research findings are limited in this area. But, proper medication, plenty of fluids certainly could have helped. Prophylactic platelet concentrate (PC) was administered to my uncle without much success, which aligns with one of the literature findings6 suggesting that PC or Fresh frozen plasma (FFP) administration needs more clinical trials to build an evidence for its application.

If that were the case, what is the solution to avoid similar such cases in the future?

At this point in time, with limited information on the mechanism of action along with non-availability of vaccine, it is essential to implement proper surveillance methods to prevent/control mosquito outbreak.5 Further, use of full-coverage clothing, mosquito nets, and repellants, and traveling during times of the day when mosquitos’ activity is lesser would also help to prevent dengue viral infection in the first place. Post-DF, early diagnosis followed by proper treatment could potentially reduce the odds of DSS or severity of DSS, thus giving the patient scope to recover. 

References: 

1.     http://www.who.int/csr/resources/publications/dengue/012-23.pdf

2.     http://cmr.asm.org/content/11/3/480.full

3.     http://www.cdc.gov/Dengue/resources/Dengue&DHF%20Information%20for%20Health%20Care%20Practitioners_2009.pdf

4.     http://www.ncbi.nlm.nih.gov/pubmed/1509881

5.     http://www.mayoclinic.org/diseases-conditions/thrombocytopenia/basics/treatment/con-20027170

6.     http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005504/pdf/1516-8484-rbhh-36-02-00100.pdf

Additional useful references on this topic collected part of this research work (Added 6/12/15)

7.   http://www.npr.org/sections/goatsandsoda/2014/12/16/370106655/hunt-for-dengue-vaccine-gets-closer

8.   http://www.livescience.com/41213-dengue-fever-outbreak-key-west-tucson.html (Dengue in Florida, but not in Arizona)

9.   http://www.healthmap.org/site/diseasedaily/article/dengue-epidemic-brazil-51315 (Dengue in Brazil)

10. http://www.ncbi.nlm.nih.gov/pubmed/25161356 (Platelet transfusion and Dengue Fever)

11. http://www.ncbi.nlm.nih.gov/pubmed/8687212 (Dengue associated ARDS)

12. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190475/?report=reader (Dengue Encephalitis)

13. http://www.ncbi.nlm.nih.gov/pubmed/1509881 (Dengue Encephalopathy)

14. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117638/ (Intracranial hemorrhage and Dengue fever)

15. http://www.healthmap.org/dengue/en/

16. http://www.msn.com/en-us/news/us/top-20-worst-mosquito-cities-in-us-summer-heat-rain-spur-mosquito-activity/ar-BBkoyZj 


Note: This article was written more to create awareness on the topic of Dengue Hemorrhagic Fever. Even qualified and knowledgeable individuals have very little understanding in terms of Dengue virus/DSS/DHF. For that reason, some sections of the article especially involving medical terms/treatment methods were replicated in the same way as presented in the original articles. I have cited those articles as well at the end.