Emergence of new lineage of Dengue virus 3 (genotype III) in Lucknow, India.

BACKGROUND AND OBJECTIVES: Dengue has re-emerged as an important arboviral disease causing significant morbidity. It has become hyperendemic in the Indian subcontinent with all four known dengue serotypes circulating. MATERIALS AND METHODS: Multiple sequence alignments and phylogenetic trees of DENV-3 were constructed to determine the extent of the isolated dengue virus genetic heterogeneity and phylogeny. RESULTS: Sequencing and phylogenetic analysis of the C-prM gene junction revealed an active circulation of a new lineage of DENV-3 (genotype III) in this region of India. CONCLUSION: Continuous epidemiological surveillance to monitor the incursion and spread of dengue virus genotypes in this region of India is needed.

Assessment of World Health Organization definition of dengue hemorrhagic fever in North India.

BACKGROUND: Classification of symptomatic dengue according to current World Health Organization (WHO) criteria is not straightforward. In this prospective study of dengue infection during an epidemic in India in 2004, we applied the WHO classification of dengue to assess its usefulness for our patients. METHODOLOGY: The study included 145 clinically suspected cases of dengue infection of all ages. Dengue was confirmed by serological methods (IgM ELISA and HI test). WHO criteria were applied to classify dengue positive patients into Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). Clinical and laboratory parameters were compared between dengue patients with bleeding and those without bleeding. RESULTS: Out of the 50 serologically positive cases of dengue enrolled in the study, only 3 met the WHO criteria for DHF and 1 met the criteria for DSS; however, 21 (42%) cases had one or more bleeding manifestations. CONCLUSION: By using WHO criteria of DHF on Indian patients, all severe cases of dengue cannot be correctly classified. A new definition of DHF that considers geographic and age-related variations in laboratory and clinical parameters is urgently required.

Randomized, controlled trial of oral ribavirin for Japanese encephalitis in children in Uttar Pradesh, India.

BACKGROUND: Japanese encephalitis is associated with high rates of mortality and disabling sequelae. To date, no specific antiviral has proven to be of benefit for this condition. We attempted to determine the efficacy of oral ribavirin treatment for reducing early mortality among children with Japanese encephalitis in Uttar Pradesh, India. METHODS: Children (age, 6 months to 15 years) who had been hospitalized with acute febrile encephalopathy (a < or =2-week history of fever plus altered sensorium) were tested for the presence of immunoglobulin M antibodies to Japanese encephalitis virus with commercial immunoglobulin M capture enzyme-linked immunosorbent assay. Children with positive results were randomized to receive either ribavirin (10 mg/kg per day in 4 divided doses for 7 days) or placebo syrup through nasogastric tube or by mouth. The primary outcome was early mortality; secondary outcome measures were early (at hospital discharge; normal or nearly normal, independent functioning, dependent, vegetative state, or death) outcome, time to resolution of fever, time to resumption of oral feeding, duration of hospitalization, and late outcome (> or =3 months after hospital discharge). The study was double-blind, and analysis was by intention to treat. RESULTS: A total of 153 patients were enrolled during a 3-year period; 70 patients received ribavirin, and 83 received placebo. There was no statistically significant difference between the 2 groups in the early mortality rate: 19 (27.1%) of 70 ribavirin recipients and 21 (25.3%) of 83 placebo recipients died (odds ratio, 1.10; 95% confidence interval, 0.5-2.4). No statistically significant differences in secondary outcome measures were found. CONCLUSIONS: For the dosage schedule used in our study, oral ribavirin has no effect in reducing early mortality associated with Japanese encephalitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00216268 .

Descriptive epidemiology of dengue transmission in Uttar Pradesh.

We report epidemiology of dengue infection as revealed through a hospital based surveillance for dengue infection over a 3 year period in Lucknow, U.P., India. In 2003-2005, children with acute febrile encephalopathy (AFE) and in 2005-2006, children with acute undifferentiated febrile illness (AUFI) were enrolled. IgM antibodies to dengue were tested by ELISA in acute serum. A total of 118/563 (20.9%) patients tested positive for dengue antibodies. Dengue transmission occurred round the year in the Lucknow region with peak in postmonsoon season and occurred equally in rural and urban areas. All the surrounding districts were affected, with no distinct high prevalence areas.

Prevalence of dengue infection in north Indian children with acute hepatic failure.

UNLABELLED: Hepatic manifestations of dengue viral infection are well known and cases of acute hepatic failure (AHF) with evidence of dengue infection are reported. OBJECTIVES: To study the role of dengue infection in AHF presenting to hospital. SETTING: Pediatric wards of a teaching hospital in northern India. SUBJECTS: Consecutive children hospitalized with AHF over a 3 month period in 2006. Clinical and laboratory details of subjects were charted. ELISA tests for dengue IgM were done in all patients using commercial kits. Real time PCR assays for dengue genome were done in randomly chosen subjects from those testing positive and negative for IgM. A PCR positive case was considered as definite dengue infection, while those who were only IgM positive were considered as 'probable' dengue. RESULTS: Between July and September 2006, 27 patients were enrolled. Thirteen were unequivocally positive for dengue IgM. A random sample of 7 IgM positive and 3 IgM negative patients was tested by PCR, of which 4 IgM positive and one IgM negative patients were PCR positive. Prevalence of definite dengue infection in AHF was therefore 5/27 or 18.5%. No significant differences were observed in clinical and laboratory features of dengue and nondengue aHF. CONCLUSIONS: Dengue infection should be considered in the etiology of AHF in this part of the world. Clinico-laboratory differentiating features of dengue AHF should be studied in a larger sample of patients.

Dengue encephalopathy in children in Northern India: clinical features and comparison with non dengue.

BACKGROUND: Acute febrile encephalopathy (AFE) is a common cause of childhood hospital admissions in Lucknow. In recent years, many patients have been hospitalized with AFE and hemorrhagic manifestations, some of whom were proven to have dengue viral infection. OBJECTIVES: To (i) define the role of dengue encephalopathy (DE) as a cause of AFE in children in Lucknow, (ii) document features of dengue hemorrhagic fever (DHF) in them and (iii)compare clinical features of definite dengue and non dengue AFE. STUDY DESIGN: Prospective study at a teaching hospital in northern India. Children between 1-12 years of age hospitalized with fever and altered consciousness of 2 weeks or less duration were enrolled after excluding bacterial and tuberculous meningitis and frank hepatic encephalopathy. Clinical and laboratory details were charted. Haemagglutination inhibition (HI) test for dengue and Japanese encephalitis viruses in paired sera and IgM antibody capture ELISA for dengue were done. Real time PCR was done in those samples testing positive for dengue IgM. Those with either positive HI test or positive dengue PCR in CSF or serum were considered definite dengue infection and features of DHF were charted in them. Those negative for IgM antibodies after 5 days of illness or whenever done, HI test, were considered definite non dengue. Clinical and laboratory features were compared between definite dengue and non dengue groups. RESULTS: A total of 265 patients of AFE were enrolled over a 2 year period. HI test was positive in 15/49 (30.6%) and IgM in 52/238 (21.8%) patients thus tested. A total of 62 patients were positive for dengue antibodies by either test. Real time PCR assay for dengue virus genome was positive in 28/42 (69%) tested -- 21/29 (72.4%) in CSF and 9/15 (60%) in serum. A total of 39 patients met the criteria for definite dengue infection of which only 2 fulfilled the WHO criteria for DHF. Comparing DE and non DE, rash, bleeding, swelling over body, and hepatomegaly were significantly more common and meningeal signs less frequent in DE. Mean platelet counts and serum albumen were lower and liver enzymes and INR were significantly higher in DE. CONCLUSIONS: Dengue viral infection is a cause of AFE in children in this region. Majority of DE here appears to be due to viral invasion of brain as suggested by high PCR positivity in CSF and lack of WHO criteria for DHF. Differentiating features of DE include swelling and hepatic dysfunction.

Limited clinical utility of pain drawing in assessing patients with low back pain.

OBJECTIVE: The aim of this study was to assess the use of pain drawing by studying its ability to identify patients with low back pain and abnormal psychological profile. The intraevaluator repeatability of the penalty point method of scoring of pain drawing was also evaluated. METHODS: A total of 331 consecutive patients with low back pain were prospectively recruited. The psychologic profile was assessed using the Hospital Anxiety and Depression Scale. The pain drawings were scored with the penalty point method. The ability of pain drawing to identify patients with significant anxiety and depression was assessed by calculating the sensitivity, specificity, and positive predictive value. The intraevaluator repeatability was calculated for scoring done at an interval of 1 month using the kappa statistic. RESULTS: There were statistically significant differences in the anxiety and depression scores in patients with normal (n = 200) and abnormal (n = 131) pain drawing (anxiety: 9 +/- 4 vs 10.3 +/- 3.7; depression: 8.1 +/- 3.5 vs 8.8 +/- 3.6; P < 0.005). The pain drawing had a low sensitivity for detecting patients with any degree of anxiety (43%) or depression (40%). The positive predictive value of pain drawing for anxiety and depression was 78% and 69%, respectively. The kappa value for intraobserver assessment was 0.6 (P < 0.05). CONCLUSION: Though there are differences in anxiety and depression scores in patients with normal and abnormal pain drawing, the performance characteristics of pain drawing are less than acceptable and therefore limit its use in clinical practice.