Development research that contributes to saving lives of patients with severe fever with thrombocytopenia syndrome (SFTS)

Severe fever with thrombocytopaenia syndrome (SFTS) is a tick-borne viral haemorrhagic fever with a high case fatality rate. Clinicians, veterinarians and scientists are working together to elucidate its pathophysiology and develop effective vaccines and treatments. The work is led by Dr Masayuki Saijo from the National Institute of Infectious Diseases (NIID) and also involves researchers from Yamaguchi University, Ehime University and Yamaguchi Grand Medical Center. The team is investigating the maintenance of the SFTS virus in nature by exploring the relationship of the virus between animals and ticks and the researchers are also working to clarify the pathophysiology of the disease, which will lead to the development of diagnostics, specific treatments and additional treatments and contribute to the further development of a vaccine. The researchers believe that a 'one health' approach to tackling SFTS is crucial, which is why they are tackling human and animal treatment and prevention in parallel. Favipiravir is an antiviral agent developed by Dr Yosuke Furuta from Toyama Chemicals and is the primary candidate for treatment. The team believes that if favipiravir can be administered to patients in the early stages of SFTS, this will reduce the case fatality rate of the disease. So far, the team has developed two recombinant vaccine candidates for SFTS that have so far demonstrated no major adverse effects. The researchers plan to develop other types of vaccines that will be safe for humans and animals.

Domestic risk factors for increased rodent abundance in a Lassa fever endemic region of rural Upper Guinea

Lassa fever (LF) is a viral haemorrhagic fever endemic in West Africa and spread primarily by the multimammate rat, Mastomys natalensis. As there is no vaccine, reduction of rodent-human transmission is essential for disease control. As the household is thought to be a key site of transmission, understanding domestic risk factors for M. natalensis abundance is crucial. Rodent captures in conjunction with domestic surveys were carried out in 6 villages in an area of rural Upper Guinea with high LF endemicity. 120 rodent traps were set in rooms along a transect in each village for three nights, and the survey was administered in each household on the transects. This study was able to detect several domestic risk factors for increased rodent abundance in rural Upper Guinea. Regression analysis demonstrated that having > 8 holes (RR = 1.8 [1.0004–3.2, p = 0.048), the presence of rodent burrows (RR = 2.3 [1.6–3.23, p = 0.000003), and being in a multi-room square building (RR = 2.0 [1.3–2.9], p = 0.001) were associated with increased rodent abundance. The most addressable of these may be rodent burrows, as burrow patching is a relatively simple process that may reduce rodent entry. Further study is warranted to explicitly link domestic rodent abundance to LF risk, to better characterize domestic risk factors, and to evaluate how household rodent-proofing interventions could contribute to LF control.

Filovirus Neutralising Antibodies: Mechanisms of Action and Therapeutic Application

Filoviruses, especially Ebola virus, cause sporadic outbreaks of viral haemorrhagic fever with very high case fatality rates in Africa. The 2013–2016 Ebola epidemic in West Africa provided large survivor cohorts spurring a large number of human studies which showed that specific neutralising antibodies played a key role in protection following a natural Ebola virus infection, as part of the overall humoral response and in conjunction with the cellular adaptive response. This review will discuss the studies in survivors and animal models which described protective neutralising antibody response. Their mechanisms of action will be detailed. Furthermore, the importance of neutralising antibodies in antibody-based therapeutics and in vaccine-induced responses will be explained, as well as the strategies to avoid immune escape from neutralising antibodies. Understanding the neutralising antibody response in the context of filoviruses is crucial to furthering our understanding of virus structure and function, in addition to improving current vaccines & antibody-based therapeutics.

Immunoinformatics Analysis and In-silico Design of Multi- Epitopes Vaccine Against Lassa Virus

Lassa virus, an arenavirus, represents the most prevalent human pathogen causing viral haemorrhagic fever. It is endemic in Nigeria and other West African countries. Despite the high burden of the disease, limited treatments are available and no approved vaccine for the prevention of this disease is available. In this study, an immunoinformatics approach was used to predict response of B and T cells from the Lassa virus proteome (GPC, NP, L and Z). The designed chimeric vaccine was modeled, refined, validated and docked with the RIG-I receptor. The docked complex of vaccine-RIG-I was subjected to dynamic stability test and the results suggest that the complex is stable. Validation of the final vaccine construct was done through in silico cloning using E. coli as host. A CAI value of 0.99 suggests that the vaccine construct expressed properly in the host. Immune simulation predicted significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ and IL-2. This theoretical study suggests infection control by creating an effective immunological memory against Lassa virus infections. However, both in vitro and in vivo experiments are needed to validate the immunogenicity and safety of the chimeric vaccine.

‘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.

Epidemiological trends of Lassa fever in Nigeria from 2015-2021: A review

Introduction: Lassa fever is a viral haemorrhagic fever with non-specific symptoms that has shown an upward trend in Nigeria and other West African countries, which is depicted by high incidence and case fatality in recent years. There are different reports on the yearly case burden of Lassa fever from the Federal Ministry of Health in Nigeria, through the regulatory body – Nigeria Centre for Disease Control (NCDC). Being the epicentre of the disease, Lassa fever has been exported from Nigeria to both neighbouring and distant countries.Methods: The aim of this review was to carry out a retrospective analysis from January 2015 to 26 September 2021 of the weekly and yearly outbreak of Lassa fever in Nigeria based on selected publications. The focus was on timely diagnosis, treatment option, public health interventions and progress of clinical trials for vaccine candidates, and to identify proactive measures that can be sustained to curb periodic outbreaks. The review was done using percentages, cross-tabulation and graphical charts. Results: The predominant age group infected was 21 to 40 years with a male to female ratio of 1:0.8. A total of 3311 laboratory-confirmed Lassa fever cases out of 20,588 suspected cases were identified from 29 states. Edo, Ondo, Taraba, Ebonyi, Bauchi, Plateau and Nasarawa had yearly Lassa fever incidence over the time frame considered. Contact tracing was done on over 33,804 individuals with about 90% completing follow-up. Case fatality rate within the period ranged from 9.3% to 29.2%. There is a sharp decline in the epidemiological trend of Lassa fever in the yearly seasonal peaks from weeks 1 to 13 with about 75% reduction in incidence between 2020 and 2021. Conclusion: The effective management of Lassa fever needs the implementation of preventive methods, prompt laboratory diagnosis, timely treatment, provision of personal protective equipment, cross-border surveillance, contact tracing, community awareness and vector control in order to minimise spread.

Tick-borne viral haemorrhagic fever infections.

This expert opinion discusses a group of tick-transmitted viruses that can cause a bonafide haemorrhagic fever in the human incidental host. It also discusses the potential impact of climatic change on virus-vector-host dynamics and on the distribution and intensity of disease.

Viral Haemorrhagic Fever Epidemics and Health Workers: Investigating the Level of Preparedness in a Tertiary Hospital in Nigeria

Aim: This study assessed the state of infection prevention and control (IPC) with an emphasis on a hospital’s preparedness for mitigating the spread of viral haemorrhagic fevers (VHFs) to staff. Methods: This convergent parallel mixed-methods study obtained data on IPC using an observational checklist in clinical departments and units; key informant interviews of stakeholders; and a structured self-administered questionnaire with frontline health workers. Both qualitative and quantitative data analyses were conducted to determine the IPC practice and level of preparedness of the hospital for the threat of VHFs. Results: The frontline clinical staff who responded to the questionnaires were aged 31 – 40 years (53.8%), male (50.3%) and medical doctors (72.2%). Some of the respondents had received training in hand washing (41.5%), use of PPE (35.1%) and standard precaution for VHFs (26.8%). Fewer respondents consistently used gloves (36.8%), face masks (8.6%), aprons (8.5%) and sharps containers (26.7%) during patient care. Amenities available for IPC varied across the 184 clinical service points in the hospital’s 19 departments. More service points had waste bins (86%), washing sinks (80%) and running water (74%) while a few had a standard operating procedure for hand washing (6%) and cabinets for storing PPEs (12%). The most significant challenge to the use of IPC measures was the inadequacy of amenities such as full PPE gear, respirator, aprons, and face masks within the clinical service points. Conclusion: There is a poor level of preparedness for outbreaks of VHFs and this calls for strengthening administrative, engineering and environmental control in health facilities to stem outbreaks among health.