Insight on the role of imaging in Lassa fever vaccine clinical trials in sub-Saharan Africa

¹Department of Radiology, Irrua Specialist Teaching Hospital, Irrua, Nigeria, ²Institute of Viral and Emergent Pathogens Control and Research, Irrua Specialist Teaching Hospital, Irrua, Nigeria, ³Department of Obstetrics & Gynecology, Irrua Specialist Teaching Hospital, Irrua, Nigeria, ⁴Department of Internal Medicine, Irrua Specialist Teaching Hospital, Irrua, Nigeria, ⁵Department of Pediatrics, Irrua Specialist Teaching Hospital, Irrua, Nigeria

^&Corresponding author
Stephen Ohikhuemei Izevbekhai, Department of Radiology, Irrua Specialist Teaching Hospital, Irrua, Nigeria

Commentary    

Lassa fever is a zoonotic disease caused by the Lassa virus which is transmitted by the multi-mammate rat (Mastomys natalensis). It is a lethal viral hemorrhagic fever endemic in the West African sub-region. Several cases have been recorded in Nigeria, Sierra Leone, Liberia and Guinea [1-3]. The disease burden is particularly high in Nigeria especially in states like Edo, Ondo, Delta, Benue, Cross River, Bauchi and Abuja- the Federal Capital territory. Its prevalence is estimated at about 100,000 to 300,000, with approximately 5000 deaths occurring yearly [4]. Although, majority of cases (80%) may be asymptomatic or mild, the virus can cause severe disease in approximately 20% of patients, sometimes associated with multiple organ failure [5].

At our own hospital- one of Nigeria´s leading Infectious disease hospitals, the case fatality from the recent 2023/2024 outbreak season was about 16.1%. Over the years, there have been successive outbreaks of Lassa fever infection, with more geographic spread which has refused to abate despite the institution of various public health and social measures at curtailing infectious disease outbreaks and spread.

Lassa fever vaccine clinical trial

More recently, there has been so much discussion by critical stakeholders on the best collaborative and transdisciplinary approach at curtailing the disease, and this seem to favour the call for the development of an effective vaccine which could completely eradicate the Lassa virus rather than just the routine preventive practices and case management protocol; hence the birth of the “LASSA FEVER VACCINE CLINICAL TRIAL INITIATIVE”[6]. This initiative is a product of the collaborative effort between the International AIDS Vaccine Initiative (IAVI), European and Developing Countries Clinical Trials Partnership (EDCTP), Coalition for Epidemic Preparedness Innovations (CEPI), and various institutions in sub-Saharan Africa, North America and Europe, with the mandate to conduct a Phase II b clinical trial of a novel vaccine candidate within various trial sites in Nigeria, Liberia and Sierra Leone. The clinical trial aims to generate proof-of-concept data to support product licensure and future access, while the research partnership will further strengthen the capacity of investigation sites where the Lassa Fever outbreaks frequently occur. The development of an effective vaccine for Lassa Fever will be a crucial tool in controlling and curtailing future outbreaks [6]. Clinical trials are the cornerstone of modern medicine which provides the scientific evidence to treat patients safely and effectively [7]. According to the World Health Organization, clinical trials aims at evaluating new tests and treatments, as well as their effects on human health outcomes. Clinical trials also determines whether a new drug is safe and potent for people to use [8,9].

Relevance of imaging

Constituting an effective multidisciplinary clinical team which would be saddled with the responsibility of Clinical data collection and management, monitoring of trial subjects for adverse events and complications, and also the treatment of trial subjects in the event of the latter becomes very imperative. Such a team should include in its membership; the Principal investigator, Clinical Research Coordinator, study physicians, clinical trial nurses, clinical trial pharmacist, regulatory coordinator, trial monitors, data managers and programmers etc. When available, it is imperative that a Radiologist should be amongst the clinical trial team. Radiological imaging is not routinely included in many vaccine trials which has been conducted in sub-Saharan Africa, and in some other instances they are under-utilized in the assessment of trial subjects.

The development of a new drug is an expensive process which requires enormous resources and is estimated to cost hundreds of millions of US Dollars. To ensure that clinical trials are conducted safely, promptly and effectively, their conduct should be open to innovation and improved methodology such as inclusion of Imaging assessments of trial subjects and other essential imaging standards in the design of study protocols by the Investigators and their Sponsors [10,11].

Although, the detection of Lassa virus disease is usually laboratory-based using the polymerase chain reaction testing (PCR), the use of imaging tools such as ultrasonography, conventional radiography, computed tomography, and Magnetic resonance imaging is of proven benefits in the assessment of multi-organ damage in Lassa fever patients. Imaging can also be used in the assessment of treatment response and the degree of recovery. Imaging appearances of organ systems can be used as biomarkers for assessing response to new drugs or assessment of severity of an emerging adverse event or its progression. Early detection of organ changes may also facilitate the early initiation of treatment measures which no doubt would contribute to reduction in mortality, reduction of disease burden, and overall improvement in patient survival outcome.

The availability of appropriate radiodiagnostic equipments and their applicability by a Radiologist during clinical trials could facilitate the detection of subtle organ changes, new structural lesions, emerging complications, evaluation of disease severity, detection of comorbidities, monitoring of treatment, as well as short and long term follow-up of subjects for untoward effects of a new drug. Ultrasonography in particular confers a myriad of advantages including it being readily available, affordable, non-ionizing, has good soft tissue resolution and its capability of assessing superficial and deep seated structures for any structural abnormality including their vascular characteristics. These advantages makes it a particularly suitable point-of-care imaging tool for assessment of trial subjects in the multi-centre Lassa fever vaccine clinical trial to be conducted in some selected hospitals in Sub-Saharan Africa.

In addition, the use of nuclear imaging technology such as Positron emission tomography (PET), and Single photon emission tomography (SPECT) may be helpful in in vivo monitoring of drug distribution, characterization of the pharmacodynamics and pharmacokinetic properties of a new drug under study [12]. As such, one would agree that imaging could open up new frontiers in clinical trials, and the applicability of modern Imaging tools tends to even do more good in clinical trials and other research. Imaging can detect pleural effusion, pericardial effusion, acute and chronic renal disease changes, lung changes- pulmonary edema, pulmonary haemorrhage, hemothorax, intracranial/intracerebral hemorrhages, and also thrombosis of the deep veins [2,3]. It is therefore pertinent that an unfettered support be provided to all imaging departments in Infectious disease hospitals especially in Sub-Saharan Africa where the Lassa fever virus is endemic and has continued to wreak havoc on human existence. This would help build human and infrastructural capacity which can further enrich the experience of Radiologists and other clinicians who are involved in the multidisciplinary care of Lassa fever patients.

Also, the establishment of Interventional Radiology subunits in the parent Radiology departments and Infectious Disease Institutes in Sub-Saharan Africa, would offer minimally invasive alternatives in the management of some complications in critically ill Lassa fever patients, and reduce the duration of hospital stay, while also seeking to reduce to the barest minimum complications from open procedures, and at same time prevent infection spread to staff and other patients.

It is pertinent to note that the main objectives of Imaging in Lassa Fever Vaccine Clinical trials would therefore include assessment of vaccine safety- by monitoring subjects for potentially imaging-detectable lesions or organ-system changes, evaluation of vaccine efficacy- by monitoring disease severity and progression amongst study participants, identification of Imaging biomarkers to help predict disease severity and treatment outcome, and also to possibly investigate vaccine-induced immune responses- by studying immune cell activation and distribution (here, functional imaging using PET/SPET scanning may be applicable). Adequate funding of Imaging units, and the provision of modern radiological equipments for Lassa fever vaccine clinical trials in Infectious disease hospitals within sub-Saharan Africa, would provide researchers more insights into vaccine safety, vaccine efficacy, and a better understanding of the dynamics of Lassa fever disease pathogenesis. When properly harnessed, pre and post-vaccination imaging assessment of clinical trial subjects could significantly assist the process which would ultimately usher in a breakthrough in the quest for a long-awaited potent vaccine to halt the deadly scourge of Lassa fever!

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Stephen Ohikhuemei Izevbekhai conceptualized and wrote the original draft. Anthony Owolabi and Pamela Faith Isioma Irabor also contributed to the conceptualization and the editing of the original draft. Joseph Okoeguale, Cyril Erameh, Peter Okokhere, Sylvanus Akhaluefo Okogbenin, George Obozokhale Akpede and Reuben Agbons Eifediyi, edited and reviewed the final draft. All the authors read and approved the final version of this manuscript.

Acknowledgments     

The authors wish to acknowledge the efforts of all Physicians and Staff at the Institute of Viral and Emergent Pathogens Control and Research in Irrua, who work all-round the clock combating the scourge of Lassa fever virus infection. We also wish to use this medium to thank the amiable and indefatigable Chief executive of our Institution (ISTH)- Prof Reuben Agbons Eifediyi; whose perchant for excellence and desire to find a lasting solution to the perennial outbreak of Lassa virus disease is indeed an inspiration to tap from. We also acknowledge the Principal Investigator in the Lassa fever vaccine Clinical trial at our Institution- Prof. Sylvanus Okogbenin, and also our veterans- Prof George O. Akpede, Prof Felix Okogbo, Prof Peter Okokhere and Prof Danny Asogun. Their fervent commitment to the control of Lassa fever, and their numerous pioneer research activities pertaining to Lassa virus disease, laid the foundation for the current Lassa fever vaccine clinical trial at our institution.

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