Unique neurological manifestations of dengue virus in pediatric population: a case series

Dengue infection is endemic in developing countries posing a major public health problem. Clinical manifestations form a broad spectrum and include uncomplicated dengue fever, dengue hemorrhagic fever and dengue shock syndrome. We report three confirmed cases of dengue infection in pediatric population with central nervous system involvement with certain unreported manifestations resulting in diagnostic dilemma. Increasing evidence of neurotropism by dengue virus emphasizes that clinician be aware of such association and consider dengue infection in cases of febrile encephalitis and myelitis in endemic areas. Early diagnosis and appropriate supportive cars can reverse this potentially fatal disease.     

Outbreak of dengue in Mumbai and predictive markers for dengue shock syndrome

An alarming rise of dengue has been seen in Mumbai during the post-monsoon season. We undertook this prospective study in the pediatric wards and pediatric intensive care unit of B. J. Wadia Hospital for Children between 27 August 2003 and 10 October 2003 to determine the clinical features, laboratory abnormalities, and outcome of children affected with dengue and to determine the predictive markers for dengue shock syndrome. Fifty-one suspected dengue cases were tested for positivity of dengue by determination of dengue IgM antibodies by ELISA test. These positive cases were analysed for common clinical features, laboratory derangements, and outcome. Patients were subdivided into three subgroups: dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) as per WHO classification. Predictive markers for DSS were also determined. Thirty-nine patients had a positive dengue IgM titre, 20 patients had DHF, 18 patients had DSS, and one patient had DF The mean age of presentation was 4.9 years. Fever, hepatomegaly, vomiting, bleeding tendencies, erythematous rash, thrombocytopenia, elevated liver enzymes, and deranged PT and PTT were the predominant clinical and laboratory features. Predictive markers for DSS were younger age at onset, altered sensorium, paralytic ileus, and significantly deranged PT. Patients with DSS also had a longer recovery period and required more supportive management in the form of component therapy and ionotropic support. All three patients who died belonged to the DSS subgroup with case fatality rate for DSS being 16.6 per cent. None of the patients in the DHF or DF subgroup died. Endemicity of dengue fever is on the rise in Mumbai with increased incidence among children. Appropriate investigations, strict monitoring and prompt supportive management can reduce mortality in dengue. Predictive markers of DSS can reduce the mortality if promptly treated. Also prevention of transmission by mosquito control and maintaining water sanitation is required to effectively control this epidemic.     

Profile of dengue patients admitted to a tertiary care hospital in Mumbai

Dengue is a mosquito-borne arboviral infection that has become a public health concern in India and particularly Mumbai, where endemicity is on the rise. Fifty-seven children having dengue infection admitted over 12 months (2008) in a child health unit of a teaching hospital in Mumbai and who were positive for IgM antibodies by ELISA test were retrospectively studied for clinical profile and outcome. Common clinical findings were fever (100%), hepatomegaly (66.6%), vomiting (40.3%), and significant bleeding manifestations (38.5%). Common laboratory findings were thrombocytopenia (platelet < 100,000/mm3 in 96.5% patients), increased liver enzymes (59.6%), hypoalbuminemia (50.8%), hyponatremia (40.3%), and deranged prothrombin time/partial thromboplastin time (PT/PTT) (33.3%). Third spacing in the form of ascites and pleural effusion was present in 15.7% and 31.5% of patients, respectively. There was no correlation between platelet count and bleeding manifestation. Patients with dengue shock syndrome required more supportive therapy with blood products and inotropes and had a longer recovery time. Mortality in the study was 3.5%. PT/PTT, serum sodium, albumin, and white blood cell (WBC) counts were predictors of severity of dengue. To summarize, fever, hemorrhagic manifestations, hepatomegaly, thrombocytopenia, and evidence of plasma leakage (hemoconcentration, pleural effusion, ascites or hypoproteinemia) should lead a clinician to suspect dengue infection.     

Pericardial effusion in dengue haemorrhagic fever

Acute shock in severe dengue haemorrhagic fever (DHF) may occur concurrently with accumulation of fluid in serous body spaces such as pleural, peritoneal and pericardial cavities. Echocardiography is a non-invasive diagnostic procedure which is sensitive to detect even a small quantity of pericardial effusion. The chest radiogram in two reported cases of DHF associated with severe shock revealed that almost half of the pleural cavity was filled with fluid. Although no signs of pericardial effusion could be determined on physical examination, ECG and radiological procedures, a small amount of fluid was clearly seen on echocardiogram.     

Natural history of plasma leakage in dengue hemorrhagic fever: a serial ultrasonographic study

BACKGROUND: Although plasma leakage is the major cause of mortality and morbidity in patients with dengue hemorrhagic fever (DHF), a detailed assessment of the natural course of this process is still lacking. We employed serial ultrasound examination to delineate the locations and the timing of plasma leakage and to evaluate the usefulness of ultrasound in detecting plasma leakage in DHF. METHOD: Daily ultrasound examinations of the abdomen and right thorax were performed in 158 suspected dengue cases to detect ascites, thickened gall bladder wall and pleural effusions. Cases were classified into dengue fever (DF), DHF or other febrile illness (OFI) based on serology and evidence of plasma leakage including hemoconcentration and pleural effusion detected by chest radiograph. RESULTS: Ultrasonographic evidence of plasma leakage was detected in DHF cases starting from 2 days before defervescence and was detected in some cases within 3 days after fever onset. Pleural effusion was the most common ultrasonographic sign of plasma leakage (62% of DHF cases one day after defervescence). Thickening of the gallbladder wall and ascites were detected less frequently (43% and 52% of DHF cases respectively) and resolved more rapidly than pleural effusions. The size of pleural effusions, ascites and gall bladder wall thickness in DHF grade I and II were smaller than those of grade III patients. Ultrasound detected plasma leakage in 12 of 17 DHF cases who did not meet the criteria for significant hemoconcentration. CONCLUSIONS: Ultrasound examinations detected plasma leakage in multiple body compartments around the time of defervescence. Ultrasonographic signs of plasma leakage were detectable before changes in hematocrits. Ultrasound is a useful tool for detecting plasma leakage in dengue infection.     

Risk factors of dengue shock syndrome in children

This retrospective hospital-based study was conducted to evaluate the various risk factors associated with dengue shock syndrome (DSS) in patients (≤18 years of age) of dengue hemorrhagic fever (DHF). Medical records of these 483 patients with DHF (IgM serology positive) were analyzed with reference to shock for various clinical and biochemical parameters. Of the 483 children, 405 were categorized in DHF group (grade I, 282 children; grade II, 123 children) and 78 in DSS group (grade III, 59 children; grade IV, 19 children). Using univariate and multivariate logistic regression and p-value of <0.05 as significant, the presence of spontaneous bleeding, hepatomegaly, signs of capillary leakage like ascitis and pleural effusion, leucopenia <4000 mm(3) and age >5 years were found out to be significant risk factors of shock in pediatrics patients of DHF.     

Pre- and postoperative fluid management in infancy

The fluid and electrolyte management of the infant either before or following surgery is not difficult if the several principles are carefully followed: (1) Fluid requirements include maintenance therapy, correction of ongoing losses, and replacement of deficit losses. (2) Calculation for fluid requirements in the postoperative period will include maintenance therapy, correction of ongoing losses, and provision of fluid lost by internal shifts. (3) Maintenance needs for fluid in infants equals 100 to 120 mL/kg per 24 hours, and Na+ at 3 mEq/kg per 24 hours and K+ at 2 to 3 mEq/kg per 24 hours are needed. (4) Infants with pyloric stenosis should be anticipated to have hypokalemic, hypochloremic metabolic alkalosis, and dehydration. These electrolyte abnormalities should be corrected before surgery is performed. A pyloromyotomy is not an emergency procedure. (5) Ileostomy losses can equal 90 mEq/L of Na+ and up to 110 mEq/L of HCO3. Thus, adequate fluid replacement results in volume depletion and metabolic acidosis. (6) Children whose nutritional status is marginal and whose bowels cannot be used for nutrient absorption should receive their fluid and electrolyte needs as part of a total parenteral nutrition program.     

Dengue shock syndrome in newborn: a case series

Four cases of dengue shock syndrome were seen during an epidemic of dengue fever. Three cases recovered following appropriate management.     

Evaluation of vomiting in children

Vomiting is a frequently reported symptom in children and can be a presenting feature in both gastro-intestinal and non gastro-intestinal disease. Careful evaluation of all children with vomiting is essential in order to identify causes which require urgent management. Important aspects of the history include onset, frequency, duration and colour of the vomitus as well as associated gastro-intestinal, respiratory and neurological symptoms. Bilious vomiting at any age should always be taken seriously and any history of recurrent bouts of vomiting is important. A thorough examination is necessary to assess hydration status of the child and elicit other associated features such as congenital abnormalities, failure to thrive or neurological deficit. Definitive management will depend on the underlying cause and may include medical and surgical therapies. In all cases good supportive care is vital with adequate fluid and electrolyte replacement being paramount. ‘Red flag’ symptoms including early morning headache, signs of peritonism, lethargy, bulging fontanelle in infants, and persistent vomiting with poor growth or abnormal development, should point the clinician to the possibility of more sinister causes of vomiting.     

Aggressive management of dengue shock syndrome may decrease mortality rate: a suggested protocol.

OBJECTIVES: Dengue shock syndrome is a leading cause of mortality among Indian children. In January 2000, we instituted a protocol for aggressive management of children with dengue shock syndrome. The objective of this study was to compare outcomes (duration of ventilation, pediatric intensive care unit stay, incidence of acute respiratory distress syndrome, and intensive care unit and hospital mortality) before and after the protocol. DESIGN: Retrospective chart review. SETTING: Pediatric intensive care unit at a tertiary teaching hospital. PATIENTS: One hundred and fourteen patients admitted between July 1997 and December 1999 received standard therapy recommended by the World Health Organization (WHO) and were designated as the WHO guidelines group (W), whereas 96 patients admitted between January 2000 and December 2001 were treated by our protocol and designated as the protocol group (P). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The patients in each group were equally matched in terms of age, Pediatric Risk of Mortality, and number with dengue hemorrhage fever grade IV, although the platelet counts were higher in the W group compared with the P group (geometric mean 42.2, confidence interval 36.9, 48.4 vs. geometric mean 36.7, confidence interval 33.3, 40.5, p < .05). Patients in the W group received less fluids in the first hour compared with the P group (median and interquartile range 20 mL/kg, 15 and 20 vs. 30 mL/kg, 20 and 60). Fluid was actively removed less often in the W group than the P group (6 of 111 vs. 45 of 96, p < .05). There was no difference in the need for ventilation or incidence of acute respiratory distress syndrome between groups, although among dengue hemorrhage fever grade IV patients, the number requiring ventilation (17 of 30 vs. 20 of 23, p < .05) and the incidence of acute respiratory distress syndrome (9 of 30 vs. 17 of 23, p < .05) were significantly greater in the W group compared with the P group. The duration of ventilation (1.5 +/- 1.7 vs. 4.2 +/- 2.9 days, p < .05) and length of intensive care unit stay (3.0 +/- 2.8 vs. 3.4 +/- 2.9 days, p < .05) were significantly less in the W group. The pediatric intensive care unit mortality (16.6% vs. 6.3%, p < .05) was significantly higher in the W group than in the P group. CONCLUSIONS: Patients with dengue shock syndrome are at high risk of mortality due to refractory shock and multiple organ failure. Survival was better for patients in the P group. Aggressive shock management and possibly the use of judicious fluid removal may decrease mortality rates in the severest forms of dengue shock syndrome.     

Dengue virus infections

Dengue is the most important arthropod-borne viral disease of public health significance. Its geographic distribution includes more than 100 countries worldwide, where more than 2.5 billion people are at risk for dengue infections. Most people will have asymptomatic infections, but the disease manifestations range from an influenza-like disease known as dengue fever to a severe, sometimes fatal disease characterized by hemorrhage and shock, known as dengue hemorrhagic fever/dengue shock syndrome. Dengue fever and dengue hemorrhagic fever/dengue shock syndrome are caused by the dengue viruses (dengue-1, dengue-2, dengue-3, and dengue-4) transmitted from viremic to susceptible humans mainly by the bites of Aedes aegypti. There is no specific management of dengue infections, no vaccine is commercially available, and vector control is the only alternative for stopping the spread of the disease. Knowledge of several aspects of dengue infections, especially of diagnosis and vaccine development, is continuously evolving, but several issues are still unresolved.     

An epidemic of dengue hemorrhagic fever and dengue shock syndrome in children in Delhi

OBJECTIVE: To study clinical profiles and outcome of children of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) during 1996 Delhi epidemic. DESIGN: Retrospective study. SETTING: Hospital based study. METHODS: Children hospitalized from September to November 1996 were studied. All patients were diagnosed, managed and monitored according to a standard protocol. RESULTS: One hundred and thirty four children (80 (60%) males and 54 (40%) females) were studied. Sixty (45%) children were less than 6 years of age of which 12 presented during infancy. There were 92 (67%) cases of DHF and 42 (33%) cases of DSS. Common symptoms were fever (93%), abdominal pain (49%) and vomiting (68%). The commonest hemorrhagic manifestation was hematemesis (39%) followed by epistaxis (36%) and skin bleeds (33%). Hepatomegaly was observed in 97 (72%) cases and splenomegaly in 25 (19%). Serology was positive (IgM hemaglutination antibody titres > 1: 160) for dengue type 2 in 31 (80%) of 39 patients in whom sera was tested during the acute phase of illness. Mortality was 6%. Hematocrit > 40% was observed in only 25 (18%) patients and hence the management protocol was based on clinical signs and symptoms and not on hematocrit. CONCLUSIONS: A management protocol of DHF/DSS in which fluid therapy is not based on haematocrit values needs to be formulated.     

Dengue hemorrhagic fever: Clinical manifestations and management

Dengue virus infection may remain asymptomatic or manifest as nonspecific viral infection to life threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Patients with DHF/DSS have fever, hemorrhagic manifestations along with thrombocytopenia and hemoconcentration. Thrombocytopenia and hemoconcentration are distinguishing features between DHF/DSS and dengue fever (DF). Some patients with dengue fever may have significant bleed and mild thrombocytopenia but no hemoconcentration. These patients are labelled to have dengue fever with unusual bleeds. Laboratory findings in DHF/DSS include rising hematocrit, thrombocytopenia and transformed lymphocytes on peripheral smear. There may be increased transaminases, hyponatremia, transient increase in blood urea nitrogen and creatinine. In severe disease there may be lab evidence of diseamination intravascular coagulation. X-ray film of the chest may show pleural-effusion. Ultrasonogram of abdomen may detect thickened gall bladder wall with hepatomegaly and ascitis. In some patients there may be abnormality in electrocardiogram and echocardiogram. The diagnosis of DHF/DSS is based on typical clinical findings. For confirmation of dengue virus infection viral culture can be done on blood obtained from patients during early phase of illness. In later part of illness antibodies against dengue virus can be demonstrated by various techniques. The treatment of DF is symptomatic. For control of fever nonsteroidal anti-inflammatory drugs should be avoided. DHF/DSS are managed by intravenous fluid infusion with repeated monitoring of vital parameters and packed cell volume (PCV).     

Management of dengue shock syndrome. A prospective study

Since dengue hemorrhagic fever (DHF) was first reported 20 years ago, the only serious variant of the disease, dengue shock syndrome (DSS), still continues to cause a relatively high mortality. An effective yet simple management of DSS which can be carried out in every hospital is certainly necessary if the dead toll is to be reduced. Prospective study of a simple procedure in managing DSS patients in Bhayangkara Police Hospital Kediri is reported. Depends on the severity of the disease, for DHF grade III: 30 ml/kg bw Lactated-Ringer solution was given at free rate. This is followed by 20 ml/kg bw of synthetic plasma expander (Expafusin) in a rate of thrice the body weight and continued with lactated-ringer and 5% dextrose in 1/2 Saline alternately with a rate of twice the body weight per minute for the remaining first 24 hours. For DHF grade IV, the same fluids were given, except for the amount and the infusion rate. Drugs administered and medical care were all the same for both groups. A close observation, a critical assessment, and an accurate as well as a rapid action are very important factors. Totally there were 115 patients of which 8 died. The mortality rate was 7%. A better management and/or treatment has to be developed to further reduce the mortality.     

Ultrasonography as a tool in predicting the severity of dengue fever in children—a useful aid in a developing country

Background

Dengue fever accounts for significant mortality in developing countries. Dengue fever serology takes a week at least to be reported positive, thus necessitating the need for other markers of diagnosis and prognosis.

Objective

The purpose of this study was to investigate the role of ultrasonography as a tool in diagnosing and predicting the severity of dengue fever in children.

Materials and methods

This was a prospective study conducted in a tertiary pediatric centre from September 2010 to July 2012. Three hundred twenty-four children with confirmed dengue fever were compared with 422 children of suspected dengue fever. Severity of illness was graded as per WHO criteria and sonography findings were correlated to the grade of illness.

Results

Gallbladder wall thickening was seen in 75% of the children with confirmed dengue fever. A significant difference was seen between survivors and non-survivors with respect to pericholecystic fluid collection (P?=?0.002), hepatic intraparenchymal fluid (P?<?0.001), splenomegaly (P?=?0.002), splenic subcapsular fluid (P?<?0.001), peripancreatic fluid (P?<?0.001), perirenal fluid (P?<?0.001) and pericardial fluid (P?<?0.001). Other findings included ascites, pleural effusion, hepatomegaly and splenomegaly, which were present irrespective of grade of illness.

Conclusions

Ultrasonography can be used as a useful tool in developing countries to predict the severity of dengue fever in children.     

Management of Septic Shock

Septic shock is an important cause of mortality in children with sepsis. The incidence of septic shock is 2–4% of admissions in western pediatric intensive care units and 40%–67% for Indian PICUs. Early goal-directed resuscitation that includes aggressive fluid resuscitation of up to 60 mL/kg as boluses of 20 mL/kg by IV push, to achieve desired heart rates and blood pressure, has emerged as mainstay of treatment in the initial stage. Crystalloids are the preferred fluids, while colloids may be used in some situations. Fluid refractory shock warrants use of vasoactive drugs. Dopamine is the first choice. Dobutamine and low dose epinephrine are the preferred inotropic drugs while nor-epinephrine is a vasopressor. Children with cold shock and normal blood pressure may benefit from nitrosodilators like nitroprusside and nitroglycerine. Inodilators such as milrinone are also useful in this situation. Targeting clinical therapeutic end-points assists the management. Good supportive care is also essential for improving the outcomes.     

Randomized evaluation of fluid resuscitation with crystalloid (saline) and colloid (polymer from degraded gelatin in saline) in pediatric septic shock

OBJECTIVE: To compare the efficacy of crystalloid (Normal saline) and colloid (polymer from degraded Gelatin in saline Haemaccel) intravenous fluid in restoration of circulating volume in children with septic shock. DESIGN: Prospective, randomized, open-label trial. SETTING: Pediatric Emergency and Intensive Care Unit of a tertiary care referral and teaching hospital. SUBJECTS AND INCLUSION CRITERIA: Sixty patients, between 1 month to 12 years of age, with septic shock, without clinical evidence of organ failure at admission or underlying immunodeficiency. INTERVENTION: Resuscitation with normal saline or polymer from degraded gelatin (Haemaccel) in the boluses rate of 20 mL/kg till hemodynamic stabilization or if central venous pressure (CVP) exceeded 10 mmHg (fluid requirement beyond 40 mL/kg guided by BP and CVP). METHODS: Hemodynamic parameters (heart rate, capillary filling time, pulse volume, and blood pressure) were recorded before and during resuscitation, and then 2 hourly for 12 hours. Central venous pressure line was placed within first hour, soon after starting fluids. Estimation of plasma volume and body water was done at the end of first hour of fluid resuscitation. OUTCOME MEASURES: Hemodynamic stabilization (heart rate, capillary refill time, systolic BP in normal range), plasma volume at the end of fluid resuscitation and incidence of organ dysfunction. RESULTS: 31 patients were randomized to normal saline and 29 to gelatin polymer. Both the groups were similar with respect to age, gender, primary diagnosis, initial hemodynamic parameters and PRISM score. Pneumonia (n = 22; 36%), gut-associated sepsis (n = 13), and dengue hemorrhagic fever (n = 11) were the common primary diagnosis. Initial hemodynamic stabilization was achieved in all. The mean (SD plasma volume (saline--53.4 (2.0 mL/kg, gelatin polymer--53.2 (1.9 mL/kg), extracellular fluid volume, total body water and interstitial fluid volume at the end of first hour of resuscitation were similar. The requirement of inotropes, incidence of organ dysfunction and case fatality rate (Saline--29%, gelatin polymer--31%), were similar in two groups. CONCLUSION: Both normal saline and gelatin polymer solution were equally effective as resuscitation fluid with respect to restoration of plasma volume and hemodynamic stability. Normal saline upto 110 mL/kg, and gelatin polymer solution upto 70 mL/kg may be required in first hour for successful fluid resuscitation of septic shock in children.     

Dengue fever epidemic in Chennai--a study of clinical profile and outcome

Children with dengue fever presenting to the Institute of Social Pediatrics, Government Stanley Hospital, during the months of October to December 2001, were prospectively followed up for clinical profile and outcome. Commonest clinical features were fever, vomiting, bleeding, body pain and hepatomegaly. Elevated liver enzymes and low platelet counts were common laboratory findings in dengue. Hepatomegaly, positive tourniquet test, elevated haematocrit and thrombocytopenia were more common in DHF and DSS group. Retro-orbital pain was slightly more in DHF and DSS groups and there was a tendency for DSS to present at an earlier age. There was no correlation between platelet counts and bleeding in classical dengue cases.     

Use of pentoxifylline in treatment of children with dengue hemorrhagic fever

The current treatment for dengue hemorrhagic fever largely consists of supportive care. The drug pentoxifylline has been shown to blunt the proinflammatory actions of tumor necrosis factor-α, a key mediator of dengue hemorrhagic fever. We performed a pilot study evaluating pentoxifylline's effect on 55 children with dengue hemorrhagic fever. We believe our findings support the existing literature on its potential use in severe infection.     

Estimation of parenteral fluid requirements

This article reviews the normal physiologic losses of water and electrolytes from the body, the source of the loss, and the increased body loss of water associated with fever. The three different methods for estimating replacement of water and electrolyte losses are described in this review.