Single-dose VSV-based vaccine protects against Kyasanur Forest disease in nonhuman primates.

Kyasanur Forest disease virus (KFDV) is an endemic arbovirus in western India mainly transmitted by hard ticks of the genus Haemaphysalis. KFDV causes Kyasanur Forest disease (KFD), a syndrome including fever, gastrointestinal symptoms, and hemorrhages. There are no approved treatments, and the efficacy of the only vaccine licensed in India has recently been questioned. Here, we studied the protective efficacy of a vesicular stomatitis virus (VSV)-based vaccine expressing the KFDV precursor membrane and envelope proteins (VSV-KFDV) in pigtailed macaques. VSV-KFDV vaccination was found to be safe and elicited strong humoral and cellular immune responses. A single-dose vaccination reduced KFDV loads and pathology and protected macaques from KFD-like disease. Furthermore, VSV-KFDV elicited cross-reactive neutralizing immune responses to Alkhurma hemorrhagic fever virus, a KFDV variant found in Saudi Arabia.

Effectiveness of One Health approach for control of Kyasanur Forest Disease in Wayanad, Kerala, India.

BACKGROUND & OBJECTIVES: Kyasanur Forest Disease (KFD) is a vector borne haemorrhagic fever that is endemic in the Wayanad region located in Northern part of Kerala, India. The region is managing the outbreak well ever since the major epidemic of 2015. This was because of the successful implementation of One Health (OH) initiative concentrating on multisectoral collaboration between regional institutions involved in public, animal and environmental health domains. The article presents how OH was implemented for the first time in the district in the year 2015 and evaluates the degree OH-ness of the Initiative. METHODS: The OH approach involved trans-disciplinary stakeholder meetings and reviews, outbreak management and integrated surveillance targeting ticks, monkeys and humans. The degree of OH-ness used for addressing KFD during the year 2015 was evaluated following the protocol developed by the Network for Evaluation of One Health (NEOH). In detail, we (i) described the OH initiative and its system (Aim, stakeholders, action strategy) and (ii) scored different aspects of this initiative (i.e., OH-thinking, -planning, -working, -sharing, -learning, -organization), with values from 0 (=no OH approach) to 1 (=perfect OH approach). RESULTS: We obtained a median score for each aspect evaluated. We reached high scores for OH systemic organization (1.0), OH thinking (0.83) and OH working (0.83). Lower scores were attributed to OH planning (0.58), OH sharing (0.50) and OH learning (0.33). The OH index was 0.36 and OH ratio was 0.95, indicating a balance between the OH operations and supporting infrastructures. INTERPRETATION & CONCLUSION: With this we could high-light some critical issues related to communication on sharing data as well as learning gaps for consideration to control future outbreaks. The strengths and weaknesses detected may be used to refine the initiative, aiming to provide a basis for the development of shared recommendations in a more OH-oriented perspective. This model of evaluation criteria will serve to create a database of OH success stories in India that will in turn help to institutionalize the approach at ministerial level. Future India is moving towards implementing a One Health, hence, this study data will provide an ideal opportunity for all sectors to control any vector borne diseases.

In-silico design of envelope based multi-epitope vaccine candidate against Kyasanur forest disease virus.

Kyasanur forest disease virus (KFDV) causing tick-borne hemorrhagic fever which was earlier endemic to western Ghats, southern India, it is now encroaching into new geographic regions, but there is no approved medicine or effective vaccine against this deadly disease. In this study, we did in-silico design of multi-epitope subunit vaccine for KFDV. B-cell and T-cell epitopes were predicted from conserved regions of KFDV envelope protein and two vaccine candidates (VC1 and VC2) were constructed, those were found to be non-allergic and possess good antigenic properties, also gives cross-protection against Alkhurma hemorrhagic fever virus. The 3D structures of vaccine candidates were built and validated. Docking analysis of vaccine candidates with toll-like receptor-2 (TLR-2) by Cluspro and PatchDock revealed strong affinity between VC1 and TLR2. Ligplot tool was identified the intermolecular hydrogen bonds between vaccine candidates and TLR-2, iMOD server confirmed the stability of the docking complexes. JCAT sever ensured cloning efficiency of both vaccine constructs and in-silico cloning into pET30a (+) vector by SnapGene showed successful translation of epitope region. IMMSIM server was identified increased immunological responses. Finally, multi-epitope vaccine candidates were designed and validated their efficiency, it may pave the way for up-coming vaccine and diagnostic kit development.

Kyasanur Forest Disease, is our surveillance system healthy to prevent a larger outbreak? A mixed-method study, Shivamogga, Karnataka, India: 2019.

BACKGROUND: Kyasanur Forest disease (KFD) is a tick-borne zoonosis that is endemic in Karnataka. Against the backdrop of the recent geographical expansion of KFD, indicating the inadequacy of policy and surveillance systems, the present study was performed to evaluate the KFD surveillance system in Shivamogga. METHODS: US Centers for Disease Control and Prevention guidelines for surveillance system evaluation were followed. Nine attributes of the system towards its objectives were evaluated in a mixed study in Shivamogga. RESULTS: Two of three medical officers and four of six health staff at the institutions visited were found to be untrained in KFD surveillance. Integrated disease surveillance formats did not capture KFD data. Surveillance (tick, monkey, human) was mostly driven by the Health Department. Some of the critical findings of the evaluations were the absence of an animal and entomological surveillance line list, non-standardized reporting formats for human suspects, varying delays in the time-to-test across laboratories (2-16 days), and a lack of systematic data-sharing practices. Significant issues that emerged in the interview were deforestation with a change in ecosystem dynamics, limited diagnostic capacity, non-availability of point-of-care tests, outdated surveillance guidelines, a confusing surveillance perimeter (5 km), non-existing co-ownership among stakeholders, limited vaccine production capacity, and inadequate operational research. CONCLUSIONS: The system should consider integrating a One Health approach with defined ownership of activities among stakeholders. Revision of the guidelines is mandatory.

'None of my ancestors ever discussed this disease before!' How disease information shapes adaptive capacity of marginalised rural populations in India.

Smallholder farmer and tribal communities are often characterised as marginalised and highly vulnerable to emerging zoonotic diseases due to their relatively poor access to healthcare, worse-off health outcomes, proximity to sources of disease risks, and their social and livelihood organisation. Yet, access to relevant and timely disease information that could strengthen their adaptive capacity remain challenging and poorly characterised in the empirical literature. This paper addresses this gap by exploring the role of disease information in shaping the adaptive capacity of smallholder farmer and tribal groups to Kyasanur Forest Disease (KFD), a tick-borne viral haemorrhagic fever. We carried out household surveys (n = 229) and in-depth interviews (n = 25) in two affected districts-Shimoga and Wayanad-in the Western Ghats region. Our findings suggest that, despite the generally limited awareness about KFD, access to disease information improved households' propensity to implement adaptation strategies relative to households that had no access to it. Of the variety of adaptation strategies implemented, vaccination, avoiding forest visits, wearing of protective clothing and footwear, application of dimethyl phthalate (DMP) oil and income diversification were identified by respondents as important adaptive measures during the outbreak seasons. Even so, we identified significant differences between individuals in exposure to disease information and its contribution to substantive adaptive action. Households reported several barriers to implement adaptation strategies including, lack of disease information, low efficacy of existing vaccine, distrust, religio-cultural sentiments, and livelihood concerns. We also found that informal information sharing presented a promising avenue from a health extension perspective albeit with trade-offs with potential distortion of the messages through misinformation and/or reporting bias. Altogether, our findings stress the importance of contextualising disease information and implementing interventions in a participatory way that sufficiently addresses the social determinants of health in order to bolster households' adaptive capacity to KFD and other neglected endemic zoonoses.

Kyasanur Forest Disease in India: innovative options for intervention.

Kyasanur Forest Disease (KFD) is a tick-borne hemorrhagic fever of human, caused by Kyasanur forest disease virus (KFDV) in India. The tick, Haemaphysalis spinigera, has been incriminated as the vector of KFDV. In human, KFD clinically presents with high fever, frontal headache, and severe myalgia, followed by bleeding from the nasal cavity, throat, gingivae, and in some cases, gastrointestinal tract. The mortality rate in KFDV infected cases is estimated to be 3-10%. Monkeys infected with the virus also develop the disease and die. Though the incidence of KFD was found to be confined only to the sylvatic area of Shimoga district in Karnataka state in India during 1967, recent reports indicate its expanding potential to the neighboring states such as Kerala, Tamil Nadu, and Goa. The administration of an indigenous, inactivated tissue culture vaccine was found to drastically decrease the percentage of incidence; however, the recurrence of KFD in vaccinated subjects warrants innovative strategies for effective control of the infection. The present communication proposes and discusses innovative intervention strategies for the effective prevention and control of KFD in India.

Kyasanur Forest Disease vaccination coverage and its perceived barriers in Goa, India-A mixed methods operational research.

BACKGROUND: Kyasanur Forest Disease (KFD) is a highly infectious viral illness transmitted by infected ticks through contact with monkeys and other forest animals. Till date there is no definite treatment available for KFD. Hence, vaccination is considered to be an important public health intervention to control KFD. This study aimed at estimating the vaccination coverage for primary and booster doses of KFD vaccine and exploring the perceived barriers to vaccination in the affected villages of Goa, India during 2015-18. METHODOLOGY & PRINCIPAL FINDINGS: In this explanatory mixed methods study, vaccine coverage was estimated bydata obtained from the KFD vaccination registers maintained at the health centers catering to the KFD affected villages. To understand the barriers to vaccination,key informant interviews were conducted among implementing health officers, medical officers and nurses involved in vaccination. Perceptions of vaccinees and community members were studied through in-depth interviews and focus group discussions. Out of the 35,500 targeted population (6-65 years)for KFD vaccination, 32% received one dose and 13.2% received two doses. The coverage for first booster and annual booster was 4.9% and 0.5% respectively. The drop out from first to second and third doses was 57% and 85% respectively. 69% of doses were delivered during community outreach programmes and remaining at health facilities. Inadequate vaccine stock, inappropriate timing of vaccination campaign, lack of awareness and misconceptions related to indications of vaccines, travel distance for follow up doses given at community health centre and pain due to injection were perceived as reasons for poor vaccination coverage. CONCLUSIONS: KFD vaccination coverage was poor in the villages affected by KFD in Goa. Both left-out and drop-out phenomena were observed in KFD vaccination. Vaccine implementation plan has to consider suitable time for the local people, maintain adequate vaccine stock and encourage community-based vaccination campaigns instead of facility-based to achieve optimal vaccine coverage.

Use of hydrogen peroxide vapour & plasma irradiation in combination for quick decontamination of closed chambers.

BACKGROUND & OBJECTIVES: Various conventional methods such as gaseous, vapour and misting systems, fogging, manual spray and wipe techniques employing a number of chemical agents are used for decontamination of enclosed spaces. Among all these methods, use of aerosolized formaldehyde is the most preferred method due to cost-effectiveness and practical aspects. However, being extremely corrosive in nature generating very irritating fumes and difficulty in maintaining a high level of gas concentration, many laboratories prefer the vaporization of hydrogen peroxide (H 2 O 2 ) as an alternative. We present here the results of using H 2 O 2 vapour in combination with plasma irradiation for quick decontamination of closed chambers. METHODS: The present study describes a decontamination method, using plasma irradiation in combination with H 2 O 2 (5%). Effect of plasma irradiation and H 2 O 2 on the viability of bacterial spores (Bacillus subtilis), Chikungunya and Kyasanur Forest Disease viruses was assessed. RESULTS: Data suggest that with the combination of H 2 O 2 vapour and plasma irradiation, within short time (three minutes), decontamination of surfaces and space volume could be achieved. Although it showed damage of spores present on the strips, it did not show any penetration power. INTERPRETATION & CONCLUSIONS: The results were encouraging, and this method was found to be efficient for achieving surface sterilization in a short time. This application may be useful in laboratories and industries particularly, those working on clean facility concept following good laboratory and manufacturing practices.

Kyasanur Forest disease outbreak and vaccination strategy,Shimoga District, India, 2013-2014.

We investigated a Kyasanur Forest disease outbreak in Karnataka, India during December 2013-April 2014. Surveillance and retrospective study indicated low vaccine coverage, low vaccine effectiveness, and spread of disease to areas beyond those selected for vaccination and to age groups not targeted for vaccination. To control disease, vaccination strategies need to be reviewed.

Kyasanur Forest disease, India, 2011-2012.

To determine the cause of the recent upsurge in Kyasanur Forest disease, we investigated the outbreak that occurred during December 2011-March 2012 in India. Male patients >14 years of age were most commonly affected. Although vaccination is the key strategy for preventing disease, vaccine for boosters was unavailable during 2011, which might be a reason for the increased cases.

Coverage and effectiveness of Kyasanur forest disease (KFD) vaccine in Karnataka, South India, 2005-10.

BACKGROUND: Kyasanur forest disease (KFD), a tick-borne viral disease with hemorrhagic manifestations, is localised in five districts of Karnataka state, India. Annual rounds of vaccination using formalin inactivated tissue-culture vaccine have been conducted in the region since 1990. Two doses of vaccine are administered to individuals aged 7-65 years at an interval of one month followed by periodic boosters after 6-9 months. In spite of high effectiveness of the vaccine reported in earlier studies, KFD cases among vaccinated individuals have been recently reported. We analysed KFD vaccination and case surveillance data from 2005 to 2010. METHODOLOGY/PRINCIPAL FINDINGS: We calculated KFD incidence among vaccinated and unvaccinated populations and computed the relative risk and vaccine effectiveness. During 2005-2010, a total of 343,256 individuals were eligible for KFD vaccination (details of vaccination for 2008 were not available). Of these, 52% did not receive any vaccine while 36% had received two doses and a booster. Of the 168 laboratory-confirmed KFD cases reported during this 5-year period, 134 (80%) were unvaccinated, nine each had received one and two doses respectively while 16 had received a booster during the pre-transmission season. The relative risks of disease following one, two and booster doses of vaccine were 1.06 (95% CI = 0.54-2.1), 0.38 (95% CI = 0.19-0.74) and 0.17 (95% CI = 0.10-0.29) respectively. The effectiveness of the vaccine was 62.4% (95% CI = 26.1-80.8) among those who received two doses and 82.9% (95% CI = 71.3-89.8) for those who received two doses followed by a booster dose as compared to the unvaccinated individuals. CONCLUSIONS: Coverage of KFD vaccine in the study area was low. Observed effectiveness of the KFD vaccine was lower as compared to the earlier reports, especially after a single dose administration. Systematic efforts are needed to increase the vaccine coverage and identify the reasons for lower effectiveness of the vaccine in the region.

Active immunisation against human tick-borne diseases.

With the development and licensure of a recombinant vaccine for the tick-borne infection Lyme disease, more attention has been paid to other vaccines that have been used or are being developed for the prevention of other tick-borne infections. This review highlights vaccine information for Lyme borreliosis, tick-borne encephalitis (TBE), Rocky Mountain spotted fever, tularaemia, Query (Q) fever, Kyasanur Forest disease (KFD) and tick paralysis. Additionally, discussion on the use of immunisation against the tick itself is included which not only can decrease veterinary tick burdens but may also decrease the transmission of arthropod-transmitted diseases.