Bhagirathi Dwibedi

An outbreak of hand, foot and mouth disease in Bhubaneswar, Odisha.

ObjectiveTo describe the epidemiology and clinical features of cases in an outbreak of Hand, Foot and Mouth Disease (HFMD).DesignDescriptive epidemiological study.SettingHospitals and community in urban areas of Bhubaneswar city, Odisha.MethodsUpon clinical suspicion of the first case as HFMD, local pediatricians and dermatologists were sensitized for case referral to Dermatology department of Institute of Medical Science and SUM hospital (IMS&SH) for evaluation and follow up. Community survey was undertaken by household visit by the team from Regional Medical Research Centre, Bhubaneswar in an outbreak area through hospital case tracing. Blood samples were tested for hematological counts and RT PCR assay done in a subset of samples for confirmation.ResultsSeventy eight cases of HFMD were detected between September 7 and November 6, 2009. Mean age (SD) was 5.13 (4.94) years (range 4 mo-31 yrs) and both sexes were equally affected. Fever and rash were the most common presenting symptoms with the rash distributed mostly over buttocks (83.3%), knees (77.5%), both surfaces of hands and oral mucosa (78.2%). Lesions healed in Mean (SD) 8.6 (1.5) days (range 7–15 d). Recovery was complete with minimal supportive treatment but, nail shedding was noted in three children within 4–5 weeks. CA16 was confirmed as the viral agent.ConclusionChildren (5–14 yrs) were majorly affected and complete recovery without neurological complications were noted. The characteristic clinical features described will be useful for early clinical diagnosis where laboratory confirmation is not feasible.

Molecular investigations of dengue virus during outbreaks in Orissa state, Eastern India from 2010 to 2011

Dengue is one of the most important arboviral diseases in India. Orissa state in Eastern India reported the first dengue outbreak in 2010, followed by extensive outbreaks in 2011, affecting large number of people. Detailed entomological, serological and phylogenetic investigations were performed in mosquitoes and patients serum collected from dengue virus (DENV) affected areas of Orissa. The combination of DENV specific IgM capture-ELISA and reverse-transcription PCR (RT-PCR) detected high DENV positivity in serum samples. DENV was detected in mosquitoes reared from field caught pupae by RT-PCR, which confirmed the vertical transmission of DENV that may have an important role in the recurrence of dengue outbreaks. Phylogenetic analyses revealed the circulation of Indian lineage of DENV-2 (genotype-IV) and DENV-3 (genotype-III) in vectors and patients serum in Orissa from 2010 to 2011, DENV-2 being the prevailing serotype. Selection analyses within the C-prM region showed that the emergence of DENV-2 and DENV-3 in Orissa was constrained by purifying selection which suggested the role of ecological factors like mosquito density and behavior in the recurrent outbreaks. Aedes albopictus was found to be the most abundant vector in the areas surveyed, followed by Aedes aegypti. Indoor breeding spots (earthen pots) were most abundant, with high pupal productivity (38.50) and contributed maximum Aedes species in the affected areas. The DENV infection rate estimated by maximum likelihood estimate (MLE) was high for indoor breeding Aedes (4.87; 95% CI: 1.82, 10.78) in comparison to outdoor breeding Aedes (1.55; 95% CI: 0.09, 7.55). The high MLE in Ae. albopictus (4.72; 95% CI: 1.94, 9.80) in comparison to Ae. aegypti (1.55; 95% CI: 0.09, 7.54) indicated that Ae. albopictus was the main DENV vector responsible for the outbreaks. The results indicated the circulation of two virulent serotypes of DENV in Orissa, mainly by Ae. albopictus with the implication for implementation of intradomecile vector control measures to prevent the spread of dengue.

Molecular investigations of chikungunya virus during outbreaks in Orissa, Eastern India in 2010

Chikungunya virus (CHIKV), an arthritogenic alphavirus, is transmitted to humans by mosquitoes of genus Aedes, mainly Aedes aegypti and Aedes albopictus. The resurgence of CHIKV in different parts of India is a point of major public health concern. In 2010, chikungunya outbreaks with high epidemic magnitude were recorded in coastal areas of Orissa, Eastern India, affecting more than 15,000 people coupled with severe arthralgia and prolonged morbidites. Detailed entomological, serological and molecular investigation of this unprecendented outbreak was carried out by collecting and studying 1359 mosquito samples belonging to A. albopictus, A. aegypti, A. vittatus, A. edwardsii and Culex species and 220 patients serum from the affected areas. In this study, CHIKV specific IgM capture-ELISA and reverse-transcription PCR (RT-PCR) were done to detect recent infection of CHIKV in serum samples and adult mosquitoes collected from the affected areas. The high maximum likelihood estimate (MLE) (15.2) in A. albopictus mosquitoes indicated that it was the principal vector involved in transmission of CHIKV in Orissa. Phylogenetic analysis revealed that the CHIKV strains involved in the outbreak belonged to the Indian Ocean Lineage (IOL) group within the East, Central and South African (ECSA) genotype. Genetic characterization of envelope glycoprotein (E1 and E2) genes revealed that all the CHIKV isolates from Orissa had the E1-A226V mutation that enhances viral dissemination and transmissibility by A. albopictus mosquitoes along with E2-L210Q and E2-I211T mutations, which play an epistatic role with E1-A226V mutation in adaptation of CHIKV to A. albopictus by increasing its midgut infectivity, thereby favoring its vectorial capacity. Our results showed the involvement of A. albopictus vector in the recent outbreaks in Orissa and circulation of IOL strains of ECSA genotype of CHIKV with E1-A226V, E2-L210Q and E2-I211T mutations in vectors and patients serum.

Unique Hepatitis B Virus Subgenotype in a Primitive Tribal Community in Eastern India

ABSTRACT Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community of Eastern India were studied to gain insight into the genetic diversity and evolution of the virus. The Paharia tribe has remained quite separate from the rest of the Indians and differs culturally, genetically, and linguistically from the mainstream East Indian population, whose HBV strains were previously characterized. Full-length HBV DNA was PCR amplified, cloned, and sequenced. Phylogenetic relationships between the tribal sequences and reference sequences from the mainstream population were assessed, and divergence times of subgenotypes of HBV genotype D were estimated. HBV was found in 2% of the Paharias participating in the study. A predominance of hepatitis B e antigen-negative infection (73%) was observed among the Paharias, and the genome sequences of the HBV strains exhibited relative homogeneity, with a very low prevalence of mutations. The novel feature of Paharia HBV was the exclusive presence of the D5 subgenotype, which was recently identified in Eastern India. Analysis of the four open reading frames (ORFs) of these tribal HBV D5 sequences and comparison with previously reported D1 to D7 sequences enabled the identification of 27 specific amino acid residues, including 6 unique ones, that could be considered D5 signatures. The estimated divergence times among subgenotypes D1 to D5 suggest that D5 was the first to diverge and hence is the most ancient of the D subgenotypes. The presence of a specific, ancient subgenotype of HBV within an ethnically primitive, endogamous population highlights the importance of studies of HBV genetics in well-separated human populations to understand viral transmission between communities and genome evolution.

Molecular mechanisms of HPV mediated neoplastic progression

Human Papillomavirus is the major etiological agent in the development of cervical cancer but not a sufficient cause. Despite significant research, the underlying mechanisms of progression from a low-grade squamous intraepithelial lesion to high grade squamous intraepithelial lesion are yet to be understood. Deregulation of viral gene expression and host genomic instability play a central role in virus-mediated carcinogenesis. Key events such as viral integration and epigenetic modifications may lead to the deregulation of viral and host gene expression. This review has summarized the available literature to describe the possible mechanism and role of viral integration in mediating carcinogenesis. HPV integration begins with DNA damage or double strand break induced either by oxidative stress or HPV proteins and the subsequent steps are driven by the DNA damage responses. Inflammation and oxidative stress could be considered as cofactors in stimulating viral integration and deregulation of cellular and viral oncogenes during the progression of cervical carcinoma. All these events together with the host and viral genetic and epigenetic modifications in neoplastic progression have also been reviewed which may be relevant in identifying a new preventive therapeutic strategy. In the absence of therapeutic intervention for HPV-infected individuals, future research focus should be directed towards preventing and reversing of HPV integration. DNA damage response, knocking out integrated HPV sequences, siRNA approach, modulating the selection mechanism of cells harboring integrated genomes and epigenetic modifiers are the possible therapeutic targets.

Emergence of Chikungunya Virus Infection in Orissa, India

From September through October 2006, an unknown disease characterized by acute onset of fever, joint pain with or without swelling, and maculopapular rash along with fatigue was reported from three villages of Cuttack and one village of Kendrapara district of Orissa, India, by the State Health Department. Upon learning this, a team from Regional Medical Research Centre (Indian Council of Medical Research), Bhubaneswar, Orissa, conducted an epidemiological investigation in the area. Household survey was carried out and clinical examination of the symptomatic individuals (n = 1289: Kendrapara, 752; Cuttack, 537) undertaken. Based on the recorded chikungunya (CHIK) fever symptoms, a vector-borne viral disease was considered for provisional diagnosis. Blood samples were collected from 217 symptomatic individuals; to confirm the diagnosis, sera were tested for anti-CHIK antibody (immunoglobulin M), which revealed 63% (64/101) and 40% (47/116) seropositivity in the samples from Kendrapara and Cuttack district, respectively. The illness was managed with analgesics like paracetamol. No death was recorded due to the illness. Entomological survey in the areas revealed the presence of Aedes mosquitoes: aegypti, albopictus, and vittatus. The per-man-hour density of Aedes vectors ranged from 0.8 to 7.6. High larval indices, house index >17% and Breteau index >70%, also indicated Aedes breeding in the area. The investigation documented circulation of CHIK in Orissa, India, and helped to take preventive steps in the outbreak area, with the suggested vector control measures.

Association of angiotensin-converting enzyme and angiotensin-converting enzyme-2 gene polymorphisms with essential hypertension in the population of Odisha, India

Abstract Background: Hypertension is a serious health issue worldwide and essential hypertension, which includes 90–95% of the cases, is influenced by both genetic and environmental factors. Identification of these factors may help in control of this disease. The Insertion/Deletion (I/D) polymorphism in Angiotensin-Converting Enzyme (ACE) gene and rs2106809 (C > T) polymorphism in Angiotensin-Converting Enzyme 2 (ACE2) gene have been reported to be associated with essential hypertension in different populations. Aim: To investigate the association of ACE I/D and ACE2 rs2106809 polymorphisms with essential hypertension in the population of Odisha, an eastern Indian state. Subjects and methods: A total of 246 hypertensives (159 males and 87 females) and 274 normotensives (158 males and 116 females) were enrolled in the study. Detailed anthropometric data, tobacco, alcohol and food habits were recorded and 2 ml of venous blood was collected for biochemical and genetic analysis. Results: The DD genotype of ACE and TT genotype of ACE2 were significantly high among female hypertensives, while T allele of ACE2 was linked to male hypertensives. In the male population, alcohol was also identified as a potential risk factor. Conclusion: Among females, ACE I/D and ACE2 rs2106809 polymorphisms, while among males, ACE2 rs2106809 polymorphism and alcohol consumption are associated with essential hypertension in the study population.

Viral aetiology and clinico-epidemiological features of acute encephalitis syndrome in eastern India.

This study reports clinico-epidemiological features and viral agents causing acute encephalitis syndrome (AES) in the eastern Indian region through hospital-based case enrolment during April 2011 to July 2012. Blood and CSF samples of 526 AES cases were investigated by serology and/or PCR. Viral aetiology was identified in 91 (17·2%) cases. Herpes simplex virus (HSV; types I or II) was most common (16·1%), followed by measles (2·6%), Japanese encephalitis virus (1·5%), dengue virus (0·57%), varicella zoster virus (0·38%) and enteroviruses (0·19%). Rash, paresis and cranial nerve palsies were significantly higher (P < 0·05) with viral AES. Case-fatality rates were 10·9% and 6·2% in AES cases with and without viral aetiology, respectively. Simultaneous infection of HSV I and measles was observed in seven cases. This report provides the first evidence on viral aetiology of AES viruses from eastern India showing dominance of HSV that will be useful in informing the public health system.

Prevalence of genital Chlamydia infection in females attending an Obstetrics and Gynecology out patient department in Orissa.

This letter to the editor discusses Chlamydia infections and goes on to state that India still needs to adopt the practice of screening women under the age of 24 years once per year for early diagnosis and treatment of Chlamydia. It includes pilot study results from Orissa that generate evidence on this infection in this region using highly sensitive and polymerase chain reaction (PCR) tests followed by southern hybridization.

Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11-β hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha, India

Essential hypertension which accounts 90–95% of the total hypertension cases is affected by both genetic and environmental factors. This study was undertaken to investigate the association of aldosterone synthase C-344T, angiotensin II type I receptor A1166C and 11- β hydroxysteroid dehydrogenase type 2 G534A polymorphisms with essential hypertension in the population of Odisha, India. A total of 246 hypertensive subjects (males, 159; females, 87) and 274 normal healthy individuals (males, 158; females, 116) were enrolled in this study based on the inclusion and exclusion criteria. Analysis of genetic and biochemical data revealed that in this population the CT and TT genotypes of aldosterone synthase C-344T polymorphism, frequency of alcohol consumption and aldosterone levels were significantly high among the total as well as male hypertensives, while the AC and CC genotypes of angiotensin II type I receptor A1166C polymorphism were significantly high among the total as well as female hypertensives. High density lipoprotein levels were higher in male hypertensives.