Senthilkumar, V (2015) Epidemiological Analysis of Flavivirus Infections in Tamil Nadu with Specific Reference to Japanese Encephalitis Dengue and West Nile Viruses development of a novel detection system. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
Full text not available from this repository.Abstract
Acute encephalitis syndrome (AES) is a clinical condition caused by infection with viruses such as Japanese Encephalitis virus (JEV), Dengue viruses and West Nile viruses or other infectious and noninfectious causes. Acute Encephalitis Syndrome (AES) causes a great public health problem in India, occurring both in epidemics and sporadically. Globally, the magnitude of problem has been estimated to be around 50,000 cases and 10,000 deaths annually300. A confirmed etiology is generally not required for the clinical management of AES. Thus, surveillance of the above viral infections in India has focused on identifying AES cases rather than JEV, DENV and WNV cases. AES in India, especially Northern India, as per definition of WHO301,302 encompasses several other illnesses; it has malaria, enteric encephalopathy, tubercular meningitis, Dengue with neurological manifestations, scrub typhus, bacterial meningitis, etc. It surely is a mixed pot. Japanese Encephalitis, an arboviral infection, is a serious public health problem in the Asian region. Globally, it affects 67,900 people per year, of which about a third are likely to die. The change in climate, ecological imbalance, and population growth together with related demands for change in agriculture and animal rearing practices have recently intensified its threat along with that of other viral encephalitis. However, many nations still struggle for disease burden data on acute encephalitis that can be used to plan prevention and control strategies. Man is the accidental host and dead end for the transmission of the disease. In Tamil Nadu, the first clinical case of JE was observed in 1955 at Vellore in India305. The first major Outbreak of JE occurred in 1973 in Bankura & Burdwan districts of West Bengal. In1976, wide spread outbreaks were reported from Andhra Pradesh, Assam, Karnataka, Tamil Nadu, Uttar Pradesh and West Bengal. The sources of virus may be different causing almost similar symptoms. Hence, all JE cases are being reported under Acute Encephalitis Syndrome (AES) after the outbreak of JE in Gorakhpur and Basti divisions in Eastern Uttar Pradesh during 2005. It is a disease of major public health importance because of its epidemic potential and high case fatality rate. The highly affected states include Andhra Pradesh, Assam, Bihar, Goa, Karnataka, Manipur, Tamil Nadu, Uttar Pradesh and West Bengal. Outbreaks of JE, Dengue and WNV usually coincide with monsoons and post- monsoon period when the vector density is high. Early management of the disease is essential, because there is no specific treatment. High vaccine coverage along with active surveillance is essential. The ultimate objective is to prevent the disease occurrence by early diagnosis, implementation of effective control measures, high vaccine coverage with strong and active surveillance system306. Therefore in the present study the sero surveillance of AES including viruses such as Japanese Encephalitis, Dengue and West Nile viruses were investigated in to 14 districts of Tamil Nadu viz., Chennai, Thiruvallur, Kanchipuram, Thiruvannamalai, Villupuram, Cuddalore, Thanjavur, Ariyalur, Perambalur, Vellore, Trichy, Madurai, Thirunelveli and Erode. Among the districts, the maximum positive AES cases of JE and Dengue were reported in Chennai, Thiruvallur and Kanchipuram district of Tamil Nadu. The higher positive AES cases of West Nile virus were explored in Thiruvannamalai, Chennai and Thiruvallur. The age wise distribution of AES cases were analyzed and divided like 0-12, 13-18, 19-35, 36-55 and above 55. The prevalence in different age groups were statistically analyzed and represented in the figure by standard error mean. Among the age groups, the positivity was predominantly seen in the pediatric age group in all the years. Few positive cases were observed in young adults. In the years 2013 and 2014, the high positivity was observed in adults and elder age groups. The total suspected cases were statistically analyzed using linear regression in different periods from 2011 to 2014. The linear regression analysis indicates that there is an increase in sample size and the total number of suspected cases was linearly raised from 2011 to 2014. In comparison of the three viruses in AES cases the Dengue occupies higher number of samples. The sample size of all the viruses in AES in the study period 2011-14 was in the order of JEV > Dengue>West Nile viruses. But the regression scatter plot in reveals that all the 150 three flaviviruses were increase in the susceptible cases. The multiple comparison analysis of the study period infers the higher number of positivity was observed in 2013 followed by 2014.The Post hoc Dunnet statistical analysis inferred that there was significant difference was found within the groups and there was no significant difference between the groups. The one way ANOVA analysis of different age groups were analyzed in different periods of the year. The mean difference was significant in all the age groups with degrees of freedom 0.05 level. The season wise distribution of cases was statistically analyzed for their epidemiological characterization of the AES in the study period. The Japanese Encephalitis virus expresses predominantly highest positive cases in all the seasons except premonsoon. The Dengue viruses have highest positive cases in the South West and North East monsoon seasons. Less number of susceptible cases occurs during the winter and premonsoon seasons. The Positive cases of West Nile virus is highly occurring in the south west monsoon than the other seasons. The age wise and gender wise analysis were done in the study period. It was observed that the male cases were high positive and susceptible than the female cases. Especially the age group of pediatrics (0-12) and young age (12-25) group indicated high positivity than the rest of the other age groups. The year wise AES Positive cases were studied from 2011-14, totally 2559 susceptible AES cases were investigated for the screening of serum ELISA in JE, DENV and WNV viruses. Amid the susceptible cases 127 cases were confirmed positive cases for JE IGM antibodies, 60 cases were positive for serum IGM antibodies and 13 cases were positive for WNV IGM antibodies. Further the epidemiological studies indicate that there is an increase in the susceptible cases from 2011-14. But the number of positive cases was highly significant in the year 2012. Because less number of cases were screened in 2012, but high number of positives were confirmed. Similarly CSF cases were screened totally in 1792 samples. High numbers of positivity were revealed in both JEV and DENV than WNV. Further the viruses were characterized molecularly and genotypically for developing new markers for diagnosis. The positive samples were cultured in the Vero cell lines. Then it the specificity and sensitivity of the cell passages were characterized. The isolated JE virus were more sensitive in the early passages of 2 and 4, rest of the passages were less sensitive and specificity. Similarly, the Dengue virus was more attuned in the late 6th passage. But the West Nile virus was highly compatible in the 5th passage of Vero cell lines. The Virus isolated samples were then preceded for Haemagglutination in different pH (6, 6.2 and 6.4). The optimum pH of the JE virus was 6.2, Dengue and West Nile viruses were agglutinated well at the optimum pH of 6.4. The viral titre of JE viruses was observed as 1:128. Dengue viruses revealed the optimum titre of 1:256 and west Nile virus 1:32. For the rapid diagnosis, Immunofluroscence assay was attempted in the JEV, DENV and WNV. Further in the study it was standardized as the dilution of 1:10 stains good fluorescence intensity with less noise in the background. This observed dilution was further applied to the studies with the viruses isolated from clinical samples. Further in the present study, the molecular phylogeny of JEV isolates i.e. [Genbank :KJ947880] were found to be closer to the clade of Indian sequences gi|496909/India/2005/envelope, gi|239633849/India/2009/envelope and gi| 289466091/India/2011/envelope. This indicates that closer clustering, even though all of 2 isolates were from a geographically distant location or different districts of the state of Maharashtra, Kerala and Assam. This demonstrated that similarities among the isolates circulating in the 2 consecutive years 2009 and 2011. Moreover, based on the present study, stated that there had been simultaneous circulation of JEV strains in India. Similarly the Dengue strains were highly close to the clade of Taiwan (gi/25992032/Taiwan/2006/Polyprotein) (gi/25992032/Taiwan/2006/Polyprotein), Peru (gi/19071812 Peru/2002/capsid) and Sri Lanka (gi 164654854 srilanka/2015/Anchored). The above clades were highly close to the KIPM KJ947880 sequences. In the west Nile virus the phylogeny indicated that WNV 1 and 2 were highly homologous with the clade of Madagascar (gi|58618099/ Madagascar/2006/polyprotein) and USA (gi|27735298/ USA/2012/unnamed). Further the strain was also homologous (94%) with Israel (gi|290246783/Israel/2011/polyprotein) and USA gi|158516889/ USA/2015/unnamed). Finally, this indicates that the same type of West Nile strains was circulated in India. Further the strains were exposed due to the patients recently migrated in the homologues countries and spread in Southern part of India.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | Epidemiological Analysis, Flavivirus Infections, Tamil Nadu, Specific Reference, Japanese Encephalitis Dengue, West Nile Viruses development, novel detection system. |
| Subjects: | MEDICAL > Community Medicine |
| Depositing User: | Subramani R |
| Date Deposited: | 18 Jan 2022 08:49 |
| Last Modified: | 18 Jan 2022 08:49 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/19009 |
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