|Year : 2021 | Volume
| Issue : 3 | Page : 199-205
Assessment of effectiveness of Japanese encephalitis vaccination in West Bengal, India using sample positivity rate as an alternate measure
Debjit Chakraborty1, Surajita Banerjee2, Dipankar Maji3, Tushar Kanti Dey4, Kulothungan Vaitheeswaran5, Palash Mondal2, Prashanta Biswas3, Falguni Debnath6, Pranab Chatterjee6
1 Integrated Disease Surveillance Programme, State Surveillance Unit, West Bengal; National Institute of Cholera and Enteric Disease (NICED), Indian Council of Medical Research (ICMR), Kolkata, India
2 Integrated Disease Surveillance Programme, State Surveillance Unit, West Bengal, India
3 Directorate of Health Service, Public Health Branch, Government of West Bengal, India
4 All India Institute of Hygiene and Public Health, Kolkata, West Bengal, India
5 National Centre for Disease Informatics and Research (NCDIR), Indian Council of Medical Research (ICMR), Bengaluru, India
6 National Institute of Cholera and Enteric Disease (NICED), Indian Council of Medical Research (ICMR), Kolkata, India
|Date of Submission||04-Sep-2019|
|Date of Decision||07-Aug-2020|
|Date of Web Publication||15-Feb-2022|
Dr. Falguni Debnath
Scientist C, Division of Epidemiology, ICMR-National Institute of Cholera and Enteric Diseases, P-33, CIT Rd, Scheme XM, Beliaghata, Kolkata 700010
Source of Support: None, Conflict of Interest: None
Background & objectives: Japanese encephalitis (JE), is a vaccine preventable mosquito borne arboviral disease. The State Health Department of West Bengal, India started a vaccination programme using live attenuated, single dose JE vaccine (SA-14-14-2) in children aged 1-below15 years since 2006 in five districts. The objectives were to compare Sample Positivity Rates (SPR) of Acute Encephalitis Syndrome (AES) cases for JE between vaccinated & unvaccinated districts and observe trend of SPR & Cumulative Incidence in vaccinated districts for three years.
Methods: The study was based on the analysis of surveillance data from all tested AES cases including confirmed JE (IgM ELISA) from all JE testing facilities existent in the state during the study period (2011–13). Calculation of Cumulative Incidence, Odds Ratio (OR) with 95% CI, Preventive Fraction and Chi Square for trend (for SPR) was done. Trend of incidence was assessed by linear regression.
Results: In three years, 5 vaccinated districts contributed 945 AES and 88 JE cases (SPR - 9.3%) compared to 1807 and 254 (SPR - 14.1%) JE cases in 14 unvaccinated districts. Effectiveness of vaccination was evident by gradual decline of Odds Ratio in favour of vaccinated districts. Vaccination effectiveness of 68% overall and 80% [OR = 0.20 (0.10 - 0.41)] in below 15 years were observed. Trend of SPR was found significantly declining in most of the vaccinated districts.
Interpretation & conclusion: Significant reduction in sample positivity rate over three years in most of the vaccinated districts indicated that the vaccination programme had been gradually effective.
Keywords: Japanese Encephalitis; Vaccination; Effectiveness; Sample Positivity Rate; West Bengal
|How to cite this article:|
Chakraborty D, Banerjee S, Maji D, Dey TK, Vaitheeswaran K, Mondal P, Biswas P, Debnath F, Chatterjee P. Assessment of effectiveness of Japanese encephalitis vaccination in West Bengal, India using sample positivity rate as an alternate measure. J Vector Borne Dis 2021;58:199-205
|How to cite this URL:|
Chakraborty D, Banerjee S, Maji D, Dey TK, Vaitheeswaran K, Mondal P, Biswas P, Debnath F, Chatterjee P. Assessment of effectiveness of Japanese encephalitis vaccination in West Bengal, India using sample positivity rate as an alternate measure. J Vector Borne Dis [serial online] 2021 [cited 2023 Mar 29];58:199-205. Available from: http://www.jvbd.org//text.asp?2021/58/3/199/321751
| Introduction|| |
Japanese encephalitis (JE), a vector borne flaviviral disease, is endemic to large part of Asia. The annual number of human deaths is 10000–15000, and estimated global impact from JE in 2002 was 709,000 Disability-Adjusted Life Years. JE virus belongs to Group B arbovirus and transmitted from reservoir animal to humans by bite of female culex mosquitoes. Japanese encephalitis viruses are divided into 5 genotypes (GI–GV). GI and GIII have mainly been isolated in temperate and epidemic areas. JE disease manifests in human in the form of Acute Encephalitis Syndrome (AES) and associated with high case fatality (around 25%) and varied neurological sequel in survivors. The global burden of JE is still unknown. In 2000, assuming an annual, age-group-specific incidence of 25 per 100000, Tsai estimated that in absence of vaccination 175000 cases would occur annually among Asian children aged 0–14 years in rural areas.
JE is perhaps the only mosquito-borne disease in India against which a vaccine is currently available. Although various JE vaccines are available, live attenuated SA-14-14-2, imported from China, is being used in many states of India since 2006 and the number of districts covered have increased since then. In the year 2012, the coverage of single dose vaccination with SA-14-14-2 vaccine among the age group of 1–15 years was >80%.
West Bengal, a state of eastern (between 23°00’N latitude and 87°00’E longitude) India, has 19 districts with varied endemicity to JEV. This state shares boundaries with highly endemic states of India such as Assam and Bihar. The vaccinations against JE were undertaken in five JE affected districts (Hooghly and Howrah in 2009, Paschim Midnapore in 2008, Birbhum in 2007 and Burdwan in 2006) by the State Health Department, Government of West Bengal on the basis of occurrence of sporadic cases. The vaccine was initially given in one-time Mass Campaign mode to children between 1 to 15 years followed by Routine Immunization (single dose, between 16–24 months) every year since.
A surveillance system of AES & JE has been launched under Integrated Disease Surveillance Programme (IDSP) in 2011. Hence, comparison of JE incidence before and after the initiation of vaccination would show paradoxical higher value in post-vaccination period where case detection was much more owing to presence of a sound surveillance mechanism. This mechanism was both health facility and laboratory based as AES is a clinical diagnosis and JE is a laboratory diagnosis.
With this perspective, the present study attempted to assess the effectiveness of JE vaccination in West Bengal using the Sample Positivity Rate (SPR) as an alternate measure as individual data about JE vaccination was not available because this was administered in mass vaccination mode. The objectives of the study were to compare the SPR between vaccinated and unvaccinated districts and to observe trend of SPR and Cumulative Incidence for the vaccinated districts for three years (2011–13)
| Material & Methods|| |
This was a secondary data analysis based on AES and JE surveillance data of IDSP from 2011–2013.
We considered districts as unit of study and children of 1–15 years age group of those districts were considered as study population where all the AES cases tested for JE including confirmed JE cases reported in different in laboratories of West Bengal were included in the analysis.
We assessed the effectiveness of the JE vaccination program for a reference period of 2011 to 2013. We abstracted data from IDSP records pertaining to the objectives of this study. For descriptive purpose, we referred all the AES and JE surveillance related manuals and documents available with the State health department.
Data of tested AES and confirmed JE cases was collated, cleaned and analyzed at State Surveillance Unit (SSU), IDSP. These data were reported to SSU, IDSP by different JE screening labs of West Bengal. Data on JE Vaccination status (total numbers only, not individualized data) of five districts were obtained from Reproductive and Child Health (RCH) division of the State.MS Excel 2007 and Epi Info (version 7) were used for calculation of Cumulative Incidence, Odds Ratio (OR) with 95% Confidence Interval, Preventive Fraction and Chi Square for trend (for SPR). Trend of incidence was assessed by linear regression using SPSS 16
Definition of terminologies used
Acute encephalitis syndrome
A person of any age with acute onset of fever and any of the following
- Change in mental status (confusion, disorientation, coma, inability to talk)
- New onset of seizures (excluding simple febrile seizures).
- Other early clinical findings like an increase in irritability, somnolence or abnormal behavior greater than that seen with usual febrile illness.
JE is one of the common etiologies of acute encephalitis syndrome (AES). These AES cases were screened for detection of JE IgM through IgM Capture ELISA of CSF and/ or Serum samples of AES cases after 5–7 days of onset of illness.
Sample positivity Rate (SPR) % = No. of persons whose any sample (serum/CSF) is reactive for JE IgM/ No. of persons whose any sample (serum/CSF) is tested for JE IgM* 100 %
Preventive Fraction = (1- OR) * 100 %
Cumulative Incidence = No. of JE cases / Population at risk (expressed as per million population)
Population at risk= Total population – (previously diagnosed but presently alive JE cases + number of children vaccinated) Previously diagnosed but presently alive JE cases were obtained by deducting JE deaths from JE cases detected in earlier years.
Anonymous data were analyzed. Data confidentiality was maintained throughout the study. The study was approved by the Institutional Ethical Committee of All India Institute of Hygiene & Public Health, Kolkata.
| Results|| |
Description of the AES and JE surveillance under IDSP
These AES cases were admitted in different health establishments of West Bengal and screened for JE in different laboratories of the state. There were 4 laboratories for JE testing in 2011and 2012 and 3 more laboratories started functioning in 2013. Each of the laboratories were linked to districts, and samples of AES cases from various health facilities of these districts were sent to these laboratories, directly or via District Surveillance Officers. All the laboratories followed similar testing standards and used same IgM capture ELISA kit (Mac ELISA) provided under National Vector Borne Disease Control Programme (NVBDCP) in India. Since these were the only JE screening labs in the entire state at that time, there was no chance of missing a lab confirmed JE case unless detected outside the state.
Confirmed JE is a suspect (AES) case which has been confirmed by laboratory tests. JE positivity was confirmed by IgM Capture ELISA of CSF and/ or Serum samples of AES cases after 5–7 days of onset of illness. Since diagnosis by serum alone has a risk of false positive result by other flaviviruses, hence samples were also screened for dengue.
The AES cases belonged to all 19 districts of West Bengal with varied proportions. Of these, 5 (Burdwan, Birbhum, Hooghly, Howrah and West Medinipur) were vaccinated districts. Rest 14 were considered as unvaccinated districts in the study. The baseline AES surveillance was known to be similar in all districts since 2011 as under IDSP same case definition, same reporting formats and same JE screening methodologies were followed.
Assessment of the effectiveness of JE vaccination programme
A total of 2752 cases of Acute Encephalitis Syndrome (AES) were tested for JE IgM during 2011–13 and 342 were found reactive (SPR - 12.4 %.). Out of 2752, vaccinated districts contributed 945 (i.e., 34.3%) cases and rest 1807 (65.7%) belonged to unvaccinated districts. In vaccinated districts, 88 (SPR - 9.3%) JE cases were detected in the 3 years and the same figure for unvaccinated districts was 254 (SPR - 14.1%).
In year wise comparison, similar SPR was observed in vaccinated (15.6%) and unvaccinated (15.8%) districts in 2011 (OR=1.02: 0.67 - 1.5). In 2012, SPR in vaccinated districts (6.1%) became lower than that of unvaccinated districts (8.9%) (OR= 0.67: 0.40 - 1.11). The difference widened in 2013 where SPR of vaccinated districts (6.8%) was around one third of unvaccinated districts (18.6%) (OR=0.32: 0.19 - 0.54) implying a preventive fraction of 68% (46% - 81%) [Table 1].
|Table 1: Comparison of Sample Positivity Rate (%) of JE, in all ages, between vaccinated and unvaccinated districts of West Bengal, 2011 -13.|
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In the age group below 15 years, SPR was similar (10%) in 2011 for both type of districts (OR = 1.08, 0.59 - 1.98). SPR reduced in subsequent years for vaccinated districts compared to unvaccinated with a gradual lowering of Odds Ratio. OR (0.20: 0.10 - 0.41) in 2013 was significantly protective for vaccinated districts [Preventive fraction - 80% (59% - 90 %)]. For>= 15 years, OR was significantly high (3.08, 1.56 - 6.09) in 2011for vaccinated districts. Although OR reduced gradually for in subsequent years, significant protective effect was not observed till 2013 [Table 2].
|Table 2: Comparison of Age Specific Sample Positivity Rate (%) of JE, in below and above (including) 15 years, between vaccinated and unvaccinated districts of West Bengal, 2011–13|
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All age SPR showed a significantly (p <0.0001) declining trend in vaccinated districts. Most significant decline was observed in Howrah (p <0.0001) followed by Birbhum (p = 0.014) and Burdwan (p = 0.028). However, for < 15 years, significant decline was observed in Howrah (p <0.0001) and pooled data of all vaccinated districts (p = 0.007) [Table 3].
|Table 3: Trend of Sample Positivity Rate (%) of JE, in all ages and below 15 years, in vaccinated districts of West Bengal, 2011 In the age group below 15 years, SPR was similar (10%) in 2011 for both type of districts (OR = 1.08, 0.59 - 1.98). SPR reduced in subsequent years for vaccinated districts compared to unvaccinated with a gradual lowering of Odds Ratio. OR (0.20: 0.10 - 0.41) in 2013 was significantly protective for vaccinated districts [Preventive fraction - 80% (59% - 90 %)]. For>= 15 years, OR was significantly high (3.08, 1.56 - 6.09) in 2011 for vaccinated districts. Although OR reduced gradually for in subsequent 13.|
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Overall Incidence was found to reduce in recent years in all vaccinated districts except Hooghly. Age Specific Incidence for below 15 years in 2013 was lower than 2011 in all vaccinated districts. None of these trends was found significant [Table 4].
|Table 4: Trend of Incidence (per million) of JE, in all ages and below 15 years, in vaccinated districts of West Bengal, 2011–13.|
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| Discussion|| |
Overall SPR in unvaccinated districts (14.1%) was 1.5 times of vaccinated districts (9.3%). However, we observed a gradual decrease in risk of infection among vaccinated districts over time. In the year 2011, we found a similar overall SPR and also SPR in below 15 years age group, in both vaccinated and unvaccinated districts, which could probably be explained by the fact that though in previous years 90% of the JE cases were in under 20 years age group in the vaccinated districts, mass vaccination campaigns conferred some protection owing to which the SPR remained almost similar even in below 15 years age group in these two types of districts.
Interestingly, in the year 2012, we observed a reduction in overall SPR as well as in risk of acquiring disease in both types of districts but the reduction was comparatively more in vaccinated districts. Studies done in this state also reported reduction in SPR in 2012 when compared to 2011,, though they did not compare vaccinated and unvaccinated districts, the findings were in coherent with our findings which can probably be explained by low viral transmission particularly in the year 2012. But the important finding was reduction of odds of SPR in vaccinated districts compared to the unvaccinated ones signifying the protection conferred by vaccination in below 15 years age group.
Subsequently in 2013, we observed a statistically significant risk reduction in vaccinated districts indicative of 68% (46%–81%) overall protection. In children below 15 years, the risk reduced further giving a vaccination effectiveness of 80% (59% –90%). Though other studies done in China, Nepal showed higher vaccine effectiveness, many of them relied on recall of the care providers which perhaps introduces the scope of bias,,,, and hence, generalizability of those estimations remained questionable. Study by Tandale BV demonstrated wide variation in vaccination effectiveness while capturing the individual vaccination status data by different methods (43% by card vs 72% by parental recall). Even, the post Marketing Surveillance of ICMR reported much lower vaccine efficacy in India compared to Nepal. According to this report, efficacy at 1 year was 43.1% and 35% respectively in overall and those who were not immune before vaccination though two other case control studies from northern part of India showed relatively higher effectiveness of 94.5% (Lucknow) and 84% (Gorakhpur),. Hence to overcome the limitation of reliable individual patient centric vaccination data in this study, we used the overall SPR and risk reduction as a measure to show the effectiveness of the vaccination program instead of focusing on effectiveness of the vaccine itself. Through this we could demonstrate an overall risk reduction and also the difference in risk reduction among vaccinated /unvaccinated districts signifying the effectiveness of the vaccination program. Though we found statistically significant protective effect of vaccination program in 2013 for vaccinated districts, it will be an underestimation if we interpret it as an annual variation.
Annual variation in JE transmission would have affect both type of districts. A gradual lowering of risk in favour of vaccinated districts over 3 years indicated much higher rate of reduction of SPR in the vaccinated districts. In each of these 3 years, protective effect for vaccinated districts was more in case of <15 years age group compared to age groups >=15 years and also the SPR was found to have a declining trend in most of the vaccinated districts over three years. The incidence of JE cases was also found to be gradually reducing although not statistically significant which probably may take some more years of vaccination to produce significant change in incidence. Moreover, incidence of JE largely depends on efficiency of surveillance system as all AES cases may not get captured and all captured AES cases are also not tested particularly those who died within 5–7 days of illness. Also, failure to estimate and exclude the magnitude of subclinical immune cases results in inflated estimation of population at risk and thereby underestimates the incidence
Though we suffered the limitation of not having patient centric vaccination data and also data on vaccination coverage particularly the number of children vaccinated during mass campaign, we compared the JE SPR between vaccinated and nonvaccinated districts presuming that the coverage of vaccination will always be higher in the vaccinated districts as non-vaccinated districts lack vaccination. Even studies done in northern India also reported higher vaccine efficacy in spite of a low coverage (52%) in 2006 and unknown coverage in 2010 campaigns. Hence, comparison of SPR and risk reduction data among vaccinated and unvaccinated districts actually highlights the effectiveness of the JE mass vaccination program accounting for both coverage and quality of the program.
We could not calculate accurate incidence as unreported clinical and all subclinical cases though immune, could not be excluded from population at risk while calculating incidence. All AES cases were not tested for JE particularly due to early deaths. Also, this is true for both type of districts since there is no reported variation in treatment facilities among them. Still, we consider this as a limitation owing to non-availability of facilities to assess viral markers (PCR, antigen) in routine surveillance system. JE screening by IgM may not be an appropriate method for immunocompromised cases. But identifying all such immunocompromised AES cases and testing them by antigen-based method may not be feasible and cost effective under the public health programme.
| Conclusion|| |
Effectiveness of vaccination was evident by gradual decline of Odds Ratio in favour of vaccinated districts. An effectiveness of 68% overall and 80% in under 15 years age group in 2013 was observed. Also, the significant reduction in sample positivity rate over 3 years in most of the vaccinated districts indicated that the vaccination programme had been gradually effective. The uniqueness of our study lies in the comparison of sample positivity rate of Acute Encephalitis cases for JE where all the cases were subjected to JE IgM screening. Hence all IgM negative AES cases were considered as non JE and recent sub-clinical JE (also IgM positive) cases were automatically excluded unlike healthy controls in case- control studies.
| Acknowledgements|| |
We sincerely acknowledge Director of Health Services, Government of West Bengal for providing the opportunity and support to conduct the study. We also acknowledge Joint Director of Health Services (Public Health & Communicable Disease) as well as Deputy Director of Health Service (Malaria) for continuously strengthening the surveillance system by all possible inputs, both technical and logistics. We acknowledge the contribution of Nodal Microbiologists and Data Entry Operators, IDSP of JE screening laboratories without whose sustained efforts this study could not be a reality.
Conflicts of interest: None
| References|| |
Erlanger TE, Weiss S, Keiser J, Utzinger J, Weihenmayer K. Past, Present, and Future of Japanese Encephalitis. Emerging Infectious Diseases
Mackenzie JS, Gubler DJ, Petersen LR. Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nature Medicine 2004; 10:
National vector borne disease control programme (NVBDCP) database http://www.nvbdcp.gov.in/Doc/JE-AES-Prevention- Control (NPPCJA).pdf
. (Accessed on July 29, 2019)
Campbell G L, Hills S L, Fischer M, Jacobson JA, Hoke CH, Hombach JM, et al
. Estimated global incidence of japanese encephalitis: a systematic review. Bulletin of the World Health Organization
Sharma S, Mishra D, Aneja S, Kumar R, Jain A, Vashishtha VM. Consensus guidelines on evaluation and management of suspected acute viral encephalitis in children in India. Indian Pediatrics
Sarkar A, Taraphdar D, Mukhopadhyay SK, Chakrabarti S, Chatterjee S. Molecular evidence for the occurrence of Japanese encephalitis virus genotype I and III infection associated with acute Encephalitis in Patients of West Bengal, India, 2010. Virology Journal
2012; 9: 271
Integrated Disease Surveillance Programme (IDSP)- Training Manual for Medical Officer for Hospital Based Disease Surveillance. https://idsp.nic.in/WriteReadData/OldSite/usermanaul/ manual_for_MO.pdf
. (Accessed on July 28, 2019).
Taraphdar D, Sarkar A, Mukhopadhyay BB, Chakraborty D, Khatun T, Chatterjee S. Increasing trend of Japanese encephalitis cases in West Bengal, India – a threat to paediatric population. Asian Pacific Journal of Tropical Disease
2012; 2: 358–361
Bandyopadhyay B, Bhattacharyya I, Adhikary S, Mondal S, Konar J, Dawar N, et al
. Incidence of Japanese Encephalitis among Acute Encephalitis Syndrome Cases in West Bengal, India. Bio Med Research International 2013; 2013 :1–5.
Chakraborty D, Banerjee S, Maji D, Dey TK, Mondal P, Basu M. A Descriptive Study of Japanese Encephalitis in West Bengal, India, Based on Surveillance Data: Changing Pattern Observed in Recent Years. Scholars Journal of Applied Medical Science
2015; 3: 320–328.
Sarkar A, Taraphdar D, Mukhopadhyay SK, Chakrabarti S, Chatterjee S. Serological and molecular diagnosis of Japanese encephalitis reveals an increasing public health problem in the state of West Bengal, India. Transactions of the Royal Society of Tropical Medicine and Hygiene
Hennessy S, Liu Z, Tsai TF, Strom BL,Wan CM, Liu HL, et al
. Effectiveness of live-attenuated Japanese encephalitis vaccine (SA14-14-2): a case-control study. Lancet 1996; 347:
Bista MB, Banerjee MK, Shin SH, Tandan JB, Kim MH, Sohn YM, et al
. Efficacy of single-dose SA 14-14-2 vaccine against Japanese encephalitis: a case control study. Lancet
Ohrr H, Tandan JB, Sohn YM, Shin SH, Pradhan DP, Halstead SB. Effect of a single dose of SA-14-14-2 vaccine one year after immunization in Nepalese children with Japanese Encephalitis: A case control study. Lancet
Tandan JB, Ohrr H, Sohn YM, Yoksan S, Ji M, Nam CM, et al
. Single dose of SA 14-14-2 vaccine provides long-term protection against Japanese encephalitis: a case-control study in Nepalese children 5 years after immunization. Vaccine
Kumar R, Tripathi P, Rizvi A. Effectiveness of one dose of SA 14-14-2 vaccine against Japanese encephalitis. New England Journal of Medicine
Murhekar MV, Ranjan P, Selvaraju S, Pandey A, Gore MM, Mehendale SM. Low coverage and acceptable effectiveness of single dose of Japanese encephalitis vaccine, Gorakhpur division, Uttar Pradesh, India, 2013. Journal of Infection
Tandale BV, Khan SA, Kushwaha KP, Rahman H, Gore MM. Japanese Encephalitis Vaccination Efficacy Case Control Study Group. Effectiveness of Japanese encephalitis SA 14-14-2 live attenuated vaccine among Indian children: Retrospective 1:4 matched case-control study. Journal of Infection and Public Health 2018; 11
Indian Council of Medical Research (ICMR) Minutes of the meeting of the Core Committee on Vaccines. https://jacob.puliyel.com/download.php?id=288pdf
. (Accessed on July 29, 2019)
[Table 1], [Table 2], [Table 3], [Table 4]