The Dynamics of Filovirus Infection in bats in Ghana

Lead Research Organisation: University of Cambridge
Department Name: Veterinary Medicine

Abstract

This research aims to understand the enigma of how highly virulent viruses that cause lethal outbreaks in humans can persist in bat populations, without causing obvious death and disease in these animals. While some of the reasons likely relate to immune systems targeting the specific viruses, other reasons will relate to the ecology and lifestyles of the bats that host these viruses. When these viruses, which include Ebola and Marburg, transmit into the human population, they cause significant death and disease and occasional major epidemics, as in the recent West African Ebola crisis. If we understood how the viruses persist in their wildlife reservoir, we could identify mechanisms for spillover and develop better means of reducing the likelihood of outbreaks occurring in humans.

The programme will characterise the actual Ebola- and Marburg-like viruses (termed filoviruses) that infect bats in Ghana, West Africa, where preliminary testing has provided evidence of infection with both viruses. Using data from the characterisation, we will then develop specific tests for the viruses in Ghana, rather than using tests based on viruses found in other parts of Africa. This phase of the work will also characterise variability in Ebola and Marburg, and potentially other filoviruses, in their bat hosts, thereby providing important information for strategies to control them, such as how these viruses are transmitted and the effectiveness of medical interventions. The specific assays developed will include tests to detect viral genomes, which will be able to pick-up low levels of specific viruses as well as blood tests for immune responses to detect prior infection; an important feature is that the tests will be developed against the range of filoviruses actually infecting bats in Ghana.
Using these tests and working with our long-standing veterinary collaborator in the Ghana wildlife services, we will screen infected bat roosts in Ghana over the 2 year time period of this grant to obtain a picture of how viruses transmit amongst and between different species of bats in Ghana. This will allow us to distinguish whether, for example, Ebola persists at a low level, persistently infecting roosts, or whether the virus depends on spreading waves of infection involving many different interconnected bat roosts. This basic knowledge does not currently exist for filoviruses in bats.

We will also use our new tests to investigate the presence of past infection of people in Ghana, in particular in those with livelihoods that bring them in close contact with bats (e.g. hunting).

The work will be delivered through careful collaboration between UK-based and Ghanaian scientists, with a strong capacity building focus. Cambridge University has a major capacity building Cambridge-Africa programme that includes the University of Ghana as a specific partner. Dr Osbourne Quaye, the Ghanaian virologist leading the programme there, has benefitted from a visiting fellowship as part of that programme. This proposed programme will fully resource his laboratory with molecular and serological equipment and also allow for specific training in the specialist assays that will be developed with Dr Wright in Westminster. The field studies in Ghana will be led by Dr Richard Suu-Ire, who recently completed his PhD on bat virus infections in the University of Ghana, co-supervised by Professors Wood and Cunningham.

We will also establish South-South collaborative links between our Ghanaian collaborators and the University of Makeni Infectious Disease Laboratory (UniMak IDRL), Sierra Leone. This laboratory was established during and following the Ebola epidemic in West Africa with funding from Wellcome and the support of the Cambridge-Africa program to provide capacity in the area of genomics. The equipment within the UniMak IDRL was used during the Ebola epidemic in West Africa to provide real-time sequencing capability.

Technical Summary

We aim to determine how filoviruses (e.g. Ebola, Marburg) persist in bat populations in Ghana. We will continue to study bat species, initially Rousettus aegyptiacus and Epomophorus gambianus, but also potentially Epomops franqueti and Hypsignathus monstrosus, in roosts where there is pre-existing evidence of infection.

We will use highly sensitive and specific PCR based detection to characterise the variability of filoviruses in Ghanaian bats, using specifically collected samples. We will then develop specific pseudotyped virus neutralisation assays to demonstrate and test for bat antibody responses to these detected viruses.

We will sample infected bat roosts longitudinally over the course of the grant to allow determination of the patterns of filovirus infection within them. Building on mathematical modelling frameworks, we will estimate transmission rates within these colonies and determine whether viruses persist in small populations, or whether they rely on transmission between roosts or amongst different species of bats.

The work will be delivered through collaboration between UK based and Ghanaian scientists, with a strong capacity building focus. Dr Osbourne Quaye, the Ghanaian virologist leading the programme there, has already benefitted from a visiting Cambridge-Africa fellowship programme. This programme will fully equip his laboratory for molecular virology and cell-based pseudotype virus neutralisation serological approaches and also allow for specific training in the specialist immune testing to be developed, with Dr Wright in Westminster. The field studies in Ghana will be led by Dr Richard Suu-Ire, who recently completed his PhD on bat virus infections in the University of Ghana.

We will also establish collaborative links between our Ghanaian collaborators and with the University of Makeni Infectious Disease Research Laboratory, that Goodfellow helped to develop in Sierra Leone during and following the Ebola epidemic of 2013-16.

Planned Impact

Ebola and Marburg viruses are probably the most feared human diseases across sub-Saharan Africa. Although outbreaks are not common, they sometimes cause devastating local epidemics in the human population, not to mention the widespread devastation they can cause to wildlife, including non-human primates. The recent Ebola crisis in West Africa devastated the infrastructure and economy of 3 struggling countries for a period of more than 12 months. While much attention has rightly been paid to mitigating the impact of haemorrhagic fever viruses once they have spread to the human population, very little is still known about how best to reduce the risks of outbreaks starting in the first place.

Our work will identify the patterns of transmission of Ebola and Marburg viruses, and potentially other filoviruses, in bats in Ghana and will help us to understand how these infections may spread to humans or their domestic animals. Advice that we develop regarding risks will need to take into account that risks are driven by poverty and by livelihood associated exposures; the latter will be informed by using our novel tests on archived human samples to identify potentially risky behaviours.

This project will start to address the question of how best to protect the Ghanaian population that is exposed to bats and thus to bat borne viruses. Our work in Ghana is already well connected with the Ghana Ministry of Health and we have held joint workshops on bat borne viruses with Public Health and Surveillance officials from the Ghana Government. A key individual in this programme, leading the wildlife component in Ghana, Dr Richard Suu-Ire, is closely connected with veterinary and medical officials both on the ground and at the highest level in Ghana. Using these pre-existing linkages, we will work to ensure that our ongoing studies are recognised in Ghana and that the results are communicated to relevant official bodies, and also to the communities that live around some major bat roosts. We have been working with these communities on other bat borne viral infections over much of the last 10 years.

Through linkages we have already developed, we will work with international conservation and public health bodies to ensure that the implications of our studies, both to bats and to people exposed to bats through living and livelihoods, are fully understood and any relevant findings are incorporated into international policies through bodies such as the World Health Organisation. Early management meetings will endeavour to bring in key stakeholders and consider if all key issues are being considered and covered. In terms of approach, we will work carefully with the key stakeholders from the outset to ensure maximal impact of our work, both through gaining from their insight and identification of specific questions and also through communication of outputs. Taking a careful 'pathways to impact' philosophy, we will engage with different groups throughout the grant, from WHO and the relevant Ghanaian authorities, through scientific researchers to local communities in Ghana, by email, web-based information, telephone and face to face meetings, wherever appropriate. Early discussions may also identify other stakeholders and impact pathways that have not already been considered that can then be taken up. These discussions will also frame processes and pathways to ensure constant engagement and bidirectional feedback between the grant partners and different stakeholder groups. This grant addresses an important and challenging area in sub-Saharan Africa and we will work to ensure that its impact is maximised.

Publications

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