Crimean Congo Haemorrhagic Fever (CCHF) Necessitates One Health, Treatment, and Vaccination
One Health
CCHF is now a global public health concern as the vectors and reservoirs migrate to previously vector-free areas. In the past, it was mainly of critical importance in Africa, Eastern Europe, and Asia, including the Middle East, but now, countries in Western and Southern Europe are at risk. Between 2018 and 2019 the tick Hyallomma Marginatum, a main CCHFV vector, was one of two species detected for the first time in Sweden. The immature ticks travelling on birds migrating from the south, arrived in Sweden in the early summer of 2018. With the predicted extreme climate heating, the immature ticks could grow to adulthood in a warmer Northern summer (Grandi et al., 2020).
Anti-CCHFV antibodies were first widely detected in southern Italy in 2021 in heavily infected transhumant bovine with an increasing risk of CCHFV exposure with age. Italy and France are at moderate risk of CCHF introduction and exposure (Fanelli et al., 2022; Fanelli & Buonavoglia, 2021). Spain has special experience with CCHF detection, with seven human cases positively confirmed with CCHF at a mortality rate of about 40%. Interestingly, segments of the virus genome experiencing assortment proved a good adaptation. More than one viral strain from Eastern Europe and Africa was detected in Spain (Portillo et al., 2021). Climate heating is creating more favourable conditions for the tick, and this helps their community to spread to new places (Yilmaz et al., 2023). So, humans, animals, and the environment are the components of health that decision-makers must consider when formulating strategies to tackle emerging threats.
Iraq reported an alarming increase in CCHF cases
The Middle East and North Africa, with its diverse tick species and pathogens, including CCHF, is a hotspot for infectious diseases. The situation in Iraq is particularly concerning, with the first CCHF infection reported in the late 70s. The virus was subsequently isolated from both patients and non-social-infected health professionals in 1981. The number of confirmed cases has been steadily rising, with a significant increase from 33 in 2021 to 511 PCR-confirmed cases in 2023 (Al-Tikriti et al., 1981; Majeed et al., 2021; Jafar et al.,2022; Atwan et al., 2023) Figure 1. This alarming trend should serve as a wake-up call, emphasising the immediate need for action.
Many factors could be involved in such an increase in Iraq, entry of one of the virus vectors H. anatolicum from neighbouring countries (Al-Shabbani & Al-Fatlawi 2023), uncontrolled entry of sheep and cattle from Turkey and Iran and severe climate change in Iraq as ticks tend to dehydrate themselves with higher aggressiveness to human compared to other hosts at temperature >40oC and lower humidity (Uspensky, 2019; Hagan et al., 2018). Finally, uncontrolled slaughtering, especially during cultural and religious occasions such as Eid Adha, Fitr and Ashura, could be a significant factor and usually shows increasing trends during that.
WHO Collaborating Centre of Public Health Education and Training Involvement & Action
WHOCC, as a specialised centre concerning public health threats, was interested in following these increased outbreaks, especially in Iraq, with a series of publications concerned with the increased confirmed cases and clinical picture of CCHF and autonomous predicting factors for healing (AlHilfi et al., 2023; Atwan et al., 2023). Accordingly, the WHOCC team was contacted by the Immunology and Microbiology department, SCRIPPS Research Institute, San Diego, CA, USA, to collaborate on two pioneering projects in treatment and vaccination based on samples from convalescent patients from Iraq.
The projects aim to produce monoclonal antibodies from CCHF convalescent plasma and prepare the CCHF vaccine. The collected antisera will be tested for neutralisation activity to select the highest activity sample. The work then follows Huang et al., 2013 protocol. The nominated samples will be used to isolate switch B cells. The isolated cells will be cultured, the supernatant will be harvested, lysis of cells to prepare the immunoglobulins. The protocol also includes stimulating B cells with certain cytokines to augment the production of IgG at high concentrations by the switch B cells. Switch B-cells will then be sequenced using the Sort-Seq RNA technique to select the reflection of the best epitope. The Sequence will be used to be cloned in vector backbone to prepare the DNACCHF vaccine.
Future Goals
- Preparing anti-CCHFv- monoclonal antibodies (best neutralisation activity)
- RNA sequencing of RNA sequenced switch B cells
Expected Outcomes
- Treating CCHF-infected patients, especially the severe cases, with the prepared monoclonal antibodies
- Preparing the DNA vaccines by cloning the sequence of the most triggering epitope in the vector backbone
Ethical approval is in process, and a patient consent form was prepared. A list of contacts with the patients is in progress, and we are waiting for the final official approval for the kick-off to start collecting the convalescent plasma.
Authors: Professor Zeenah Atwan and Celine Tabche
As for funding…..
we are currently preparing an application to submit to various organisations and stakeholders interested in exploring the new treatment options and vaccine we have in development, to find out more…
please contact our Teaching Fellow, Celine Tabche c.tabche20@imperial.ac.uk
….we also welcome interest from those who wish to help us tackle this outbreak through donating or sponsorship
References:
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