Pig Vaccination for Japanese Encephalitis : Time to review strategy

Pigs play a vital role in the maintenance of the transmission cycle for the Japanese Encephalitis (JE) virus. For long, vaccination of pigs against JE has been one of the approaches that have been adopted for protecting vulnerable populations against the risk of acquiring the disease. However, newer evidence and existing operational challenges make vaccination a less appealing approach to control the JE risk in India.

A time to review and assess anew
Vaccination of pigs against JE has been known to be an effective intervention to control the risk of JE in humans in several countries.However, emerging evidence is showing that there is a waning of immunologic response to existing vaccines in pigs owing to a genotype shift phenomenon which is affecting the circulating JE virus.There are major policy implications from the public health and veterinary health aspects owing to the findings emerging from recent studies which highlight the fact that swine vaccination may not be the panacea it has been made out to be in the conventional wisdom

Some global and local findings
The JE virus can be classified into five genotypes based on the similarities shown by the E gene. The predominant strain in circulation in South Asian countries was the G3 strain, based on which the veterinary vaccines have been developed. However, it is now being noted that the G1 strain has replaced the G3 strain in most biotopes in the South Asian setting. In addition, G5 strains are also being reported in vector populations in certain countries. Although it has traditionally been accepted that there is no significant difference in the immunological responses to the different strains owing to a high degree of similarity, emerging evidence is less promising. A recent study conducted in Taiwan has added to the debate by suggesting that using the current crop of G3 based vaccines can provide only a partial response against the circulating G1 serotypes. ) This finding is indeed alarming as it means that we need to conduct comprehensive field testing of the JE vaccines to better understand the real world effectiveness of the vaccines.

In a modelling study from Bangladesh, it has been found that with 30% current seropositivity in pig populations, an estimated 20% of the vulnerable pigs are likely to acquire JE infection every year. Their model also suggested that with 50% coverage of susceptible pigs, an estimated 82% reduction in pig infections could be seen. However, though these results may seem to be promising, our experience from the research activity conducted at Kushinagar leads us to believe that this experience cannot be extrapolated to the Indian setting. The pig seropositivity in Indian, endemic areas is much higher, (to the tune of 75% according to the estimates of our study) for one thing.

Another aspect is that with multiple litters being bred every year, and no way to keep track of animal movement, either during grazing/feeding or through sale/purchase, it is virtually impossible, even within a small district, to estimate the number of unvaccinated piglets and institute a vaccination programme which achieves 50% coverage. The Universal Immunization Programme for children, which is deeply integrated within the three-tier health system in India, and has had the entire machinery of the human health ministries and advocacy bodies powering it on, has achieved only moderate coverage, to the tune of 61%. With multiple cultural and economic barriers, it is therefore, difficult to imagine a 50% coverage of all susceptible swine population in India through the currently existing veterinary health infrastructure.

In addition to this, the emerging uncertainty over the immunologic validity of the currently used veterinary vaccines brings into question the need to approach JE infection in pigs using innovative, non-pharmacological public health interventions.

Introduce more non-pharmaceutical interventions
One of the major problems plaguing the control of the JE control programme in India is our inability to quantify the burden of the disease correctly. From the results of our research experience in Kushinagar, the PHFI/RCZI study team estimated that there would be over 600 cases of JE in that particular district in the given year. However, the reported number of cases was much lower.

This can be attributed to the fact that the current diagnostic tests may not be as accurate as initially believed to be; additionally, the low awareness regarding the disease and the need to approach healthcare providers when such symptoms appear may lead to missing cases.

Alongside the need to intensify case finding efforts, there is a need to establish non-pharmaceutical interventions that reduce JE transmission between pigs and from pigs to man.

The first of these is to establish strong Information-Education-Communication channels, which propagate culture-appropriate messages that help in reducing vector propagation and contact. Additionally, there is a need to push for wider adoption of insecticide treated bed nets. It has been incontrovertibly established that using ITNs over pig pens and in human habitations reduces the seroprevalence of JE in both man and pig. However, our research experience has shown that although there is universal adoption of the use of bednets, not a single of these are treated with long lasting insecticides, and none of them are used to protect the pig pens. Additionally, there is a need to understand the perceptions and practices of using bed nets as improper use may hinder control measures.

Although veterinary vaccination seems like an effective way to approach the problem of JE in India, there are severe operational constraints. Also, doubts about the immunologic efficacy of the vaccine itself, and a massive lack of effort in trying out non-pharmacological practices and behaviour change interventions must be adopted before committing investments into vaccination drives for pigs.

References
1. Sasaki O, Karoji Y, Kuroda A, Karaki T, Takenokuma K, Maeda O. Protection of pigs against mosquito-borne Japanese encephalitis virus by immunization with a live attenuated vaccine. Antiviral Res [Internet]. 1982 Dec [cited 2015 Nov 30];2(6):355–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6131643

2. Nah J-J, Yang D-K, Kim H-H, Song J-Y. The present and future of veterinary vaccines for Japanese Encephalitis in korea. Clin Exp Vaccine Res. 2015;4:130–6.

3. Fan Y-C, Chen J-M, Chen Y-Y, Lin J-W, Chiou S-S. Reduced neutralizing antibody titer against genotype I virus in swine immunized with a live-attenuated genotype III Japanese encephalitis virus vaccine. Vet Microbiol [Internet]. 2013 May 3 [cited 2015 Nov 30];163(3-4):248–56. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23415032

4. Khan SU, Salje H, Hannan A, Islam MA, Bhuyan AAM, Islam MA, et al. Dynamics of Japanese encephalitis virus transmission among pigs in Northwest Bangladesh and the potential impact of pig vaccination. PLoS Negl Trop Dis [Internet]. 2014 Sep [cited 2015 Aug 10];8(9):e3166. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4177832&tool=pmcentrez&rendertype=abstract

5. Ministry of Health and Family Welfare (India), ORG Centre for Social Research, United Nations Children’s Fund. India Coverage Evaluation Survey 2009-2010 [Internet]. 2010 [cited 2015 Aug 10]. Available from: https://nrhm-mis.nic.in/SitePages/Pub_CoverageEvaluation.aspx#

6. Dubot-Pérès A, Sengvilaipaseuth O, Chanthongthip A, Newton PN, de Lamballerie X. How many patients with anti-JEV IgM in cerebrospinal fluid really have Japanese encephalitis? Lancet Infect Dis [Internet]. Elsevier; 2015 Dec 12 [cited 2015 Nov 17];15(12):1376–7. Available from: http://www.thelancet.com/article/S1473309915004053/fulltext

7. Robertson C, Pant DK, Joshi DD, Sharma M, Dahal M, Stephen C. Comparative spatial dynamics of Japanese encephalitis and acute encephalitis syndrome in Nepal. PLoS One [Internet]. 2013 Jan [cited 2015 Aug 10];8(7):e66168. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3718805&tool=pmcentrez&rendertype=abstract

8. Dutta P, Khan SA, Khan AM, Borah J, Sarmah CK, Mahanta J. The effect of insecticide-treated mosquito nets (ITMNs) on Japanese encephalitis virus seroconversion in pigs and humans. Am J Trop Med Hyg [Internet]. 2011 Mar [cited 2015 Aug 6];84(3):466–72. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3042826&tool=pmcentrez&rendertype=abstract


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