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 ~  Materials and Me...
 ~  Results
 ~  Discussion
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Year : 2007  |  Volume : 25  |  Issue : 2  |  Page : 143-145
 

Dengue viral infections as a cause of encephalopathy


1 Department of Microbiology, Faculty of Medical Sciences, University of Jayawardenapura, Colombo 8, Sri Lanka
2 Lady Ridgeway Hospital for Children, Colombo 8, Sri Lanka
3 Department of Medicine, Faculty of Medical Sciences, University of Jayawardenapura; Colombo, Sri Lanka
4 Colombo South Teaching Hospital, Kalubowila, Sri Lanka
5 Department of Clinical Immunology, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom
6 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom

Correspondence Address:
G N Malavige
Department of Microbiology,, Faculty of Medical Sciences, University of Jayawardenapura, Colombo 8
Sri Lanka
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DOI: 10.4103/0255-0857.32722

PMID: 17582186

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 ~ Abstract 

The aim of this study was to determine the clinical characteristics and poor prognostic factors associated with high mortality in dengue encephalopathy. Fifteen patients with confirmed dengue infections, who developed encephalopathy, were recruited from two tertiary care hospitals in Colombo, Sri Lanka. Among the factors that contributed to encephalopathy were: Acute liver failure (73%), electrolyte imbalances (80%) and shock (40%). Five (33.3%) patients developed seizures. Disseminated intravascular coagulation was seen in five (33.3%). Secondary bacterial infections were observed in 8 (53.3%) of our patients. The overall mortality rate was 47%.


Keywords: Clinical presentation; dengue viral infections; encephalopathy


How to cite this article:
Malavige G N, Ranatunga P K, Jayaratne S D, Wijesiriwardana B, Seneviratne S L, Karunatilaka D H. Dengue viral infections as a cause of encephalopathy. Indian J Med Microbiol 2007;25:143-5

How to cite this URL:
Malavige G N, Ranatunga P K, Jayaratne S D, Wijesiriwardana B, Seneviratne S L, Karunatilaka D H. Dengue viral infections as a cause of encephalopathy. Indian J Med Microbiol [serial online] 2007 [cited 2014 Apr 21];25:143-5. Available from: http://www.ijmm.org/text.asp?2007/25/2/143/32722


Dengue infections may be asymptomatic or give rise to undifferentiated fever, dengue fever (DF), dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). [1] Although rare, complications such as liver failure, encephalopathy, myocarditis and acute renal failure may occur. [1] Some believe that such complications have increased in recent years. [2],[3] These atypical manifestations of dengue infections are reported to be associated with more severe grades of disease. [4] Encephalopathy is thought to occur in 0.5% [5] to 6.2% [2] of patients with DHF, with an associated mortality rate of 22%. [5]

Although encephalopathy is well-documented in dengue infections, the clinical and laboratory features associated with encephalopathy are not well defined. Furthermore, it would be useful to characterize the bad prognostic features associated with a high mortality in encephalopathy. In this report we describe clinical presentations and laboratory features of 15 patients with encephalopathy as a result of dengue infections. We have also attempted to identify the poor prognostic features in them.


 ~ Materials and Methods Top


This study was carried out in the Lady Ridgeway Hospital for Children, Colombo and in the Colombo South Teaching Hospital, Sri Lanka from April 2004 to August 2005. All patients with dengue infections who developed features of encephalopathy were included. The study was approved by the Ethics Review Committee, University of Sri Jayawardanapura, Sri Lanka. Clinical features, haematological and biochemical laboratory measurements were recorded from all patients serially, until discharged from hospital.

Dengue viral specific antibodies were detected using the PANBIO TM Dengue duo IgM and IgG rapid strip test [6] on a serum sample taken at least seven days after onset of the illness. The WHO classification and case definitions were used to categorize patients as having either DF or DHF. [7] DHF was further divided into four grades (I, II, III and IV) as per WHO definitions. Haemoconcentration was considered to be present when the packed cell volume (PCV) was > 50 in adults and >45 in children.


 ~ Results Top


During this period, 15 patients with dengue infections developed encephalopathy. Eight (60%) had grade III and six (40%) had grade IV DHF. Seven of them succumbed to their illness with a mortality rate of 47%. All of these patients received treatment in the intensive care unit. Table summarizes the clinical and laboratory features of these 15 patients. Eight (53%) patients presented with predominantly gastrointestinal tract related symptoms, such as severe abdominal pain, vomiting and diarrhoea. One adult patient was initially investigated for a surgical cause for her acute abdominal pain and another for a ruptured ectopic pregnancy due to per vaginal bleeding. A diabetic patient who presented with fever, confusion and blood glucose of 23.5 mmol/L was initially managed as having diabetic ketoacidosis/hyperosmolality.

Eleven (73%) patients had evidence of acute liver failure (ALF) with raised liver transaminases (> 20 times the upper limit of normal). The aspartate transaminase and alanine transaminase ratio in these patients ranged from 1.6 to 4.3. Five of these patients became deeply icteric. The conjugated bilirubin to unconjugated bilirubin ratio in these patients was approximately 4:1, excluding hemolysis as the cause of jaundice. All these patients had prolonged prothrombin times and activated partial thromboplastin time.

Varying degrees of altered levels of consciousness was seen in our cohort. Drowsiness, restlessness and mental confusion (Glasgow Coma scale 12-14) were the only neurological features in five patients. Six of the ten patients who were unconscious (Glasgow Coma scale 3-8) succumbed to their illness. Of the five patients who developed seizures, two had generalized seizures and three had focal seizures involving the arm, leg and eye of one side. A CT scan from one of the patients with focal seizures showed cerebral oedema of moderate degree. All of the patients with seizures had hyponatremia and later went in to profound shock and died.

All our patients had pleural effusions and ascites. Eight patients developed severe respiratory distress due to pulmonary oedema. However, four of them also had myocarditis, which could have contributed to the respiratory distress. Electrolyte abnormalities were seen in 12 patients (10 had hyponatraemia and five had hyperkalaemia). All five patients who had hyperkaemia also developed acute renal failure and metabolic acidosis. Of these five patients, all but one developed multi organ failure and succumbed to their illness. Five patients developed disseminated intravascular coagulation (DIC) as evidenced by very high levels of D dimers in their blood.

Secondary bacterial infections were observed in eight (53.3%) of our patients (septicaemia in four, pneumonia in two, ventilator associated pneumonia in one and a urinary tract infection in one). E. coli were isolated from blood cultures from those who had septicaemia and two patients with pneumonia. Oral candidiasis was detected in the oropharnyx of three children but not in any of the adult patients.


 ~ Discussion Top


We have characterized the clinical and laboratory features of a cohort of dengue patients, who developed encephalopathy. It is evident from the varying clinical features that were present on admission, that encephalopathy due to dengue infections can be easily confused with other conditions unless a high degree of suspicion is maintained. From our data it is likely that many factors such as shock, electrolyte disturbances and ALF may contribute to encephalopathy. Interestingly, in contrast to other viral infections which involve the liver, the AST levels were much higher than ALT levels as described by others. [5],[8] This difference could be due to the release of AST from skeletal muscle and the myocardium as damage to muscle in dengue infections has been reported. [9],[10]

Secondary bacterial infections and oral candidiasis was observed in the majority of patients which is a well recognized complication of severe dengue infections. [11] However, as gram negative sepsis was seen in these patients it could be argued that all of these were hospital acquired infections.

A relatively higher mortality rate (47%) was seen among our patients when compared to other case series. [5] In at least two patients, late presentation may have contributed to their deterioration. However, it is possible that the higher mortality was due to a more virulent dengue virus strain that circulated during this period. Loss of consciousness, the development of seizures and acute renal failure appear to be poor prognostic indicators.

In summary, we have reported clinical presentations and possible factors contributing to encephalopathy in patients with dengue infections. Due to the varying clinical presentations a high degree of clinical suspicion is needed in the diagnosis and management of patients with dengue infections especially during an epidemic of dengue infections.



 
 ~ References Top

1.Malavige GN, Fernando S, Fernando DJ, Seneviratne SL. Dengue viral infections. Postgrad Med J 2004; 80 :588-601.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Hendarto SK, Hadinegoro SR. Dengue encephalopathy. Acta Paediatr Jpn 1992; 34 :350-7.  Back to cited text no. 2  [PUBMED]  
3.Pancharoen C, Rungsarannont A, Thisyakorn U. Hepatic dysfunction in dengue patients with various severity. J Med Assoc Thai 2002; 85 :S298-301.  Back to cited text no. 3  [PUBMED]  
4.Souza LJ, Alves JG, Nogueira RM, Gicovate Neto C, Bastos DA, Siqueira EW, et al . Aminotransferase changes and acute hepatitis in patients with dengue fever: Analysis of 1,585 cases. Braz J Infect Dis 2004; 8 :156-63.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Cam BV, Fonsmark L, Hue NB, Phuong NT, Poulsen A, Heegaard ED. Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever. Am J Trop Med Hyg 2001; 65 :848-51.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Cuzzubbo AJ, Vaughn DW, Nisalak A, Solomon T, Kalayanarooj S, Aaskov J, et al . Comparison of panbio dengue duo enzyme-linked immunosorbent assay (ELISA) and mrl dengue fever virus immunoglobulin m capture elisa for diagnosis of dengue virus infections in southeast asia. Clin Diagn Lab Immunol 1999; 6 :705-12.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.World health Organization. Prevention and control of dengue and dengue haemorrhagic fever: Comprehensive guidelines. Who Regional Publication: Searo; 1999.  Back to cited text no. 7    
8.Kuo CH, Tai DI, Chang-Chien CS, Lan CK, Chiou SS, Liaw YF. Liver biochemical tests and dengue fever. Am J Trop Med Hyg 1992; 47 :265-70.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Davis JS, Bourke P. Rhabdomyolysis associated with dengue virus infection. Clin Infect Dis 2004; 38 :e109-11.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Malheiros SM, Oliveira AS, Schmidt B, Lima JG, Gabbai AA. Dengue. Muscle biopsy findings in 15 patients. Arq Neuropsiquiatr 1993; 51 :159-64.  Back to cited text no. 10    
11.Lee IK, Liu JW, Yang KD. Clinical characteristics and risk factors for concurrent bacteremia in adults with dengue hemorrhagic fever. Am J Trop Med Hyg 2005; 72 :221-6.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]



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