Lassa fever and carcinogenesis: emerging as new areas of concern in clinical surgery

Arenaviruses are segmented negative-sense RNA (nsRNA) viruses that are closely related to those of the Bunyaviridae and Orthomyxoviridae families. The Lassa Virus (LASV), the agent of Lassa illness, is a member of the family Arenaviridae. LASV was first identified in 1969 by a missionary nurse working at a clinic in a small community named Lassa in northern Nigeria. She had likely got contact with the virus from a LASSA-based infection of an obstetrical patient and had died within a week following the onset of her symptoms1. One of the nurses who had treated the first patient also contracted what would later become Lassa fever and died. It is estimated that between 100 000 and 300 000 people were infected with LASV annually, leading to roughly 5000 deaths. The reservoir rodent, Mastomys natalensis, may be found all over West Africa and is responsible for the spread of the LASV. Human infections have been confirmed through serology in the countries of Senegal, Guinea, Sierra Leone, Liberia, and Nigeria (Figs. 1 and 2). From the late 1970s until the early 1990s, eastern Sierra Leone was host to the sole long-term investigation of Lassa disease in all of West Africa. After repeated requests from the government of Sierra Leone to research epidemics in the eastern province, the Centers for Disease Control and Prevention (CDC) developed and funded the project2.Figure 1: Lassa fever recorded cases from 1969 to 2022.Figure 2: Spread of LASSA Fever 1969–2022.The clinical presentation, epidemiology, immunology, pathophysiology, and treatment of Lassa fever have all been elucidated throughout the years. Not only have war and social unrest over the past decade hampered ongoing research and prevented new ones from taking place, but they have also likely contributed to a rise in disease rates in these places. Between 7 and 21 days is the incubation period for Lassa fever3. The initial stages of the clinical sickness are similar to the flu, including high fever, overall weakness and overall lethargy, sore throat, cough, and severe headache. Nausea, vomiting, and diarrhea are among the common gastrointestinal symptoms that may appear early on. Despite the absence of major hemorrhagic signs, vascular dysfunction is believed to be an important part of the pathobiology of Lassa fever given its association with a dismal prognosis4. Facial edema, pleural effusions, and pericardial effusions are all symptoms of a vascular permeability problem5. Lassa fever patients typically begin to feel better 8–10 days after becoming unwell6. In extreme cases, between the 6th and 10th day of the sickness, the patient’s health rapidly deteriorates with significant pulmonary edema, acute respiratory distress, encephalopathy signs, and fatal shock. Despite being common, mucosal surface bleeding seldom causes shock. sensorineural deafness is common in severe disease or early recovery7. Arenaviridae virus Lassa is encapsulated, single-stranded, bi-segmented RNA. LASV, like other arenaviruses, lacks negative-strand coding and the virus isolates varied genetically, serologically, and pathologically. LASV is spherical and 70–150 nm wide, glycoprotein-built T-shaped spikes measure 7–10 nm on its smooth surface envelope. The single-stranded arenavirus genome has two RNA fragments, respectively. The sRNA encodes the viral glycoprotein precursor protein (GPC) and nucleoprotein (NP), while the lRNA encodes the viral polymerase and a tiny, zinc-binding (Z) protein28. New full-length sRNA amplification methods aid arenavirus identification and molecular analysis29. LASV sRNA sequencing identified and molecularly characterized four strains. Sequencing of LASV sRNA showed a lot of genomic diversity1. It can be speculated from the available data (data acquired from the CDC) that the spread of LASSA is unusual and mostly in the first six months of the year (Table 1)8. According to the climatology reports9, the temperature between December to June is 26.9–31⁰C. The temperature could be a factor; however, more research should be done to better understand this. Virus isolation is the best LASV diagnostic method, but BSL-4 biocontainment makes it unfeasible in endemic areas. ELISA or RT-PCR are the most frequent methods for detecting viral proteins or LASV-specific IgM or IgG antibodies. The immunofluorescence assay (IFA) was utilized to detect LASV antibodies; however, it required BSL-4 biocontainment, highly trained workers, and low sensitivity. Clinical and laboratory use persists. In an orthogonal diagnostic system, PCR-based molecular assays like RT-PCR give the most confidence in results10. Due to the genetic heterogeneity in LASV strains throughout a wide geographic area, primer and probe failures are more likely in PCR-based experiments. Most assays target the short RNA that encodes the GPC precursor and NP. Because LASV-specific IgG is produced later in the infection, this assay is limited in patient diagnosis11. LASV diagnostics should be simple, robust, sensitive, and affordable, considering LASV lineage genetic and geographical variability. Diagnostic advances in LASSA fever will improve treatment, control, and prevention in endemic areas. Point-of-care immunological and/or PCR-based assay equipment will soon bring diagnostics to patients to improve treatment decisions and patient outcomes. LASV antibody frequency in known and potential endemic places will improve risk maps. Metagenomics in outbreaks and rodent reservoir hosts will enhance LASV eco-epidemiology the most. This method could answer issues about LASV incidence, transmission bottlenecks, and reservoir host virus variety. Our defense against emerging and re-emerging viruses like LASV will involve a better understanding of the virus circulating in the environment, sickness in humans, and virus maintenance in rodent reservoir hosts. Diagnostics are best for LASSA fever prevention today and in the future. Table 1 - Places of origin and places where it spread between 1969 and 2022. Place of origin Places affected Recorded year Country Continent Country Continent Estimated month of infection 1969 Nigeria Africa United States North America 1971 Sierra Leone Africa United Kingdom Europe 1971 Sierra Leone Africa United Kingdom Europe 1972 Sierra Leone Africa United Kingdom Europe 1974 Nigeria Africa Germany Europe 1975 Nigeria Africa United Kingdom Europe 1975 Sierra Leone Africa United States North America March 1976 Sierra Leone Africa United States North America February 1976 Nigeria Africa United Kingdom Europe December 1980 Upper Volta Africa Netherlands Europe 1981 Nigeria Africa United Kingdom Europe 1982 Nigeria Africa United Kingdom Europe 1984 Sierra Leone Africa United Kingdom Europe 1985 Sierra Leone Africa United Kingdom Europe 1987 Liberia Africa Israel 1987 Sierra Leone Africa Japan Asia 1989 Nigeria Africa Canada North America 1989 Nigeria Africa United States North America 1994 Nigeria Africa Sierra Leone Africa 2000 Ghana/Burkina Faso/Cote d voire Africa Germany Europe 2000 Sierra Leone Africa United Kingdom Europe 2000 Nigeria Africa Germany Europe 2000 Sierra Leone Africa Netherlands Europe 2003 Sierra Leone Africa United Kingdom Europe 2004 Sierra Leone Africa United States North America March 2006 Africa Germany Europe June 2012 Nigeria Africa Nigeria Europe April 2015 Africa United States North America May 2016 Nigeria Africa Nigeria Africa May 2016 Benin Africa Benin Africa May 2016 Togo Africa Togo Africa January 2016 Africa Germany Europe February 2016 Africa Sweden Europe March 2016 Liberia Africa Liberia Africa March 2016 Burkina Faso Africa Burkina Faso Africa April 2016 Nigeria Africa Nigeria Africa April 2016 Benin Africa Benin Africa May 2017 Benin Africa Benin Africa March 2017 Togo Africa Togo Africa March 2017 Burkina Faso Africa Burkina Faso Africa March 2017 Nigeria Africa Nigeria Africa June 2018 Nigeria Africa Nigeria Africa June 2019 Nigeria Africa Nigeria Africa February 2021 Nigeria Africa Nigeria Africa March 2021 Liberia Africa Liberia Africa June 2021 Nigeria Africa United Kingdom Europe June 2021 Nigeria Africa Netherlands Europe June 2021 Sierra Leone Africa Germany Europe June 2021 Sierra Leone Africa Sierra Leone Africa June 2022 Nigeria Africa Nigeria Africa June 2022 Nigeria Africa United Kingdom Europe June 2022 Sierra Leone Africa Ireland Europe February 2022 Togo Africa Togo Africa February 2022 Guinea Africa Guinea Africa February 2022 Sierra Leone Africa Netherlands Europe March 2022 Sierra Leone Africa Sierra Leone Africa May According to the findings of an intriguing new paper, there might be a connection between the etiology of human odontogenic tumors and arenavirus infection12,13. This publication acts as both a catalyst and a call to action for future research into the role that the virus plays in the development of tumors. On the other hand, a number of studies have found evidence that the virus inhibits the growth of cancerous cells. For example, the Lassa-vesicular stomatitis chimeric virus is able to successfully eradicate brain tumors without causing any harm. In point of fact, the expressional pathway analysis indicated a common link between the pathogenesis of Lassa fever and carcinogenesis. Furthermore, it has been established that the anticancer treatment is efficient in preventing the entry of the LASV into cells14. Due to this, additional study in clinical medicine is still required in order to understand the precise nature of the relationship between the LASV and the tumor. Ethical approval Ethics approval was not required for this correspondence. Consent Informed consent was not required for this correspondence. Sources of funding Not applicable. Author contribution J.A. and M.A.B.: conceptualization; M.S. and M.M.: investigation; M.M., M.S., and J.A.: writing original draft; M.B.: writing review and editing; J.A.: supervision. Conflicts of interest disclosures The authors declare no conflicts of interest. Research registration unique identifying number (UIN) Not applicable. Guarantor Melaku Ashagrie Belete. Data availability statement Not applicable.

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