Ongoing Outbreaks of Lassa Virus in Nigeria

March 8, 2022

Context

The first known confirmed Omicron (B.1.1.529) infection was from a specimen collected on November 9, 2021 in Botswana (1). The variant rapidly began to spread to South Africa and other Southern African countries. Nigeria also experienced daily surge of COVID-19 cases in December, and Omicron became the dominant variant. Currently, cases of COVID-19 substantially are decreasing daily. However, the cases of Lassa fever are much higher than the previous epidemic seasons. This attributes to the reduced response capacity in surveillance and laboratory testing due to conversion of dedicated Lassa fever facilities into COVID-19 health-care facilities (2).

Lassa virus (LASV) is an Old World arenavirus that causes Lassa fever, an often-fatal viral hemorrhagic fever (3). It is estimated that there are approximately 100,000–300,000 clinical infections in West Africa per year, with approximately 5000 deaths (4). Case fatality estimates range from 10–69%, but can be more than 90% in the third trimester of pregnancy. Lassa fever is classified as a National Institute of Allergy and Infectious Diseases Category A Biodefense Agent (5) and is endemic to Sierra Leone, Liberia, Guinea, and Nigeria (6). Sporadic cases have been reported in other West African countries, with recent outbreaks in Togo and Benin. The natural reservoir for the virus is the Mastomys natalensis rodent (commonly known as the multimammate rat) (7). Transmission of the virus to humans occur through: (1) direct contact with urine, faces, saliva or blood of infected rats; (2) contact with objects, household items and surfaces or eating food, contaminated with urine, feces, saliva or blood of infected rats and (3) person to person transmission by contact with blood, urine, feces, vomitus, and other body fluids of an infected person (8).

Reported Cases

In Nigeria, from 3 to 30 January 2022, 211 laboratory confirmed Lassa fever cases including 40 deaths (case fatality ratio: 19%) have been cumulatively reported in 14 of the 36 Nigerian states and the Federal Capital Territory across the country (2) with majority (73%) of the infections concentrated in three states; Bauchi in the north and Edo and Ondo in the south (NCDC Lassa Fever Situation Feb 2022 report). In contrast, noticeably less Lassa fever cases with less geographical spread were reported for the same period in 2021 (54 confirmed cases, including 12 deaths, from 8 States). Nigerian health officials reported an additional 58 confirmed Lassa fever cases with the death toll of six during the first week of February (9). The annual peak of Lassa fever cases is typically observed during the dry season

the end of the dry season as illustrated in figure 1 (2). In addition, the U.K. has had three new confirmed cases of Lassa fever with one death (10). The cases are within the same family and are linked to recent travel to West Africa

Lassa virus (LASV) is an Old World arenavirus that causes Lassa fever, an often-fatal viral hemorrhagic fever (3). It is estimated that there are approximately 100,000–300,000 clinical infections in West Africa per year, with approximately 5000 deaths (4).

In Nigeria, from 3 to 30 January 2022, 211 laboratory confirmed Lassa fever cases including 40 deaths (case fatality ratio: 19%) have been cumulatively reported in 14 of the 36 Nigerian states and the Federal Capital Territory across the country (2) with majority (73%) of the infections concentrated in three states; Bauchi in the north and Edo and Ondo in the south (NCDC Lassa Fever Situation Feb 2022 report).

 Even with ongoing pandemic, our efforts must be continued for the viral surveillance of bats, pigs, and people with One Health approach and for enhancing our understanding on the ecology of Pteropus bats and the dynamics of the virus spillover event to intermediate hosts and people.

The “Enable” study

There is no licensed Lassa fever vaccine (5). Perhaps the most significant effort toward developing an effective vaccine for Lassa is the ‘Enable’ study funded by the Coalition for Epidemic Preparedness Innovations (CEPI) that plans to enroll up to 23,000 participants across five West African countries (Benin, Guinea, Liberia, Nigeria, and Sierra Leone). The ‘Enable’ study hopes to establish important epidemiological data to include spread, risk factors, and incidence that would inform joint multi-country Lassa Fever Vaccine Efficacy and Prevention for West Africa (LEAP4WA) planned by CEPI and European & Developing Countries Clinical Trials Partnership (EDCTP) across the selected West African countries (ENABLE ; LEAP4WA). The only available treatment, ribavirin, is most effective only during early infection (11). Lassa fever is most often diagnosed by using enzyme-linked immunosorbent serologic assays (ELISA), which detect IgM and IgG antibodies as well as Lassa antigen (12). Reverse transcription-polymerase chain reaction (RT-PCR) can be used in the early stage of disease. Recently, great progresses have made for treatment and prophylaxis of Lassa fever by in-depth understanding of viral protein structure. A single surface glycoprotein complex (GPC) is responsible for attachment and entry of LASV into host cells (13). GPC is a heavily N-glycosylated trimer that is composed of three non-covalently associated subunits, GP1 and GP2 and an unusual stable signal peptide (SSP). GP1 is responsible for receptor binding, while GP2 mediates fusion of the virion with a cell membrane. SSP is required for proper processing of GPC and is retained as part of the complex. As the sole antigen on the viral surface, GPC is the primary target of neutralizing antibodies (MAbs). Neutralizing monoclonal antibodies have been isolated from Sierra Leonean and Nigerian survivors of Lassa fever (6). Development of MAbs as potential Lassa immunotherapeutics was facilitated by structural studies and mutational analyses that identified protective epitopes on the prefusion form of the LASV glycoprotein (14-16). Use of structure-guided amino acid substitutions has led to increase in the neutralization potency and breadth of these antibodies to include all major LASV lineages (16). The ability to define antibody residues that allow potent and broad neutralizing activity, together with findings from analyses of inferred germline precursors, is critical to develop potent therapeutics. Antibody therapeutics may be further developed in clinical trials in endemic areas potentially offering a key treatment option for Lassa fever. In vaccine design and assessment, vaccine-driven elicitation of anti-LASV GPC-B antibodies efficiently in humans may be possible only through immunization with an engineered immunogen that faithfully and sustainably displays the prefusion trimer of LASV GPC. Further, site-selective deglycosylation of viral glycoproteins can improve immunogenicity and may be also an effective strategy for the extensively glycan-shielded Lassa virus, particularly through the incorporation of N-glycan deletions at positions 390 and 395 in the GPC (16).

Conclusion

LASV infection poses a significant healthcare burden in those living in rural areas where communities have poor sanitation and/or crowded living conditions. The major control strategy is the control of the rodents around dwellings, avoiding of rats consumption and contact (17). The lack of an approved therapeutic or vaccine, potential for geographic expansion of the rodent reservoir, ease of procurement and weaponization of the virus, and the possible emergence of new viral strains support recommendations for enhanced surveillance and preparedness for Lassa fever (6). It is necessary to continue to enhance viral surveillance effort for early detection and treatment of cases to reduce the case fatality rate.

Our GVN Team thanks Dr. Alash’le Abimiku (The Institute of Human Virology, University of Maryland) for reviewing this manuscript and for providing us with invaluable information, comments, and insights.

References

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