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Lassa virus in novel hosts: insights into the epidemiology of lassa virus infections in southern Nigeria.

ABSTRACT: Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown - specifically relating to pathogen diversity, evolution, and transmission - the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.

SUBMITTER: Happi AN

PROVIDER: S-EPMC10810657 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature

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Lassa virus in novel hosts: insights into the epidemiology of lassa virus infections in southern Nigeria.

Happi Anise Nkenjop AN Ogunsanya Olusola Akinola OA Ayinla Akeemat Opeyemi AO Sijuwola Ayotunde Elijah AE Saibu Femi Mudasiru FM Akano Kazeem K Nwofoke Cecilia C Elias Obineche Tobias OT Achonduh-Atijegbe Olivia O Daodu Richard Olumide RO Adedokun Oluwatobi Abel OA Adeyemo Abraham A Ogundana Kehinde Ebenezer KE Lawal Omolola Zaheedat OZ Parker Edyth E Nosamiefan Iguosadolo I Okolie Johnson J Parker Zahra F ZF McCauley Melanie D MD Eller Leigh Anne LA Lombardi Kara K Tiamiyu Abdulwasiu Bolaji AB Iroezindu Michael M Akinwale Edward E Njatou Thierry Lamare Fouapon Assedi TLFA Mebrahtu Tsedal T Broach Erica E Zuppe Anastasia A Prins Petra P Lay Jenny J Amare Mihret M Modjarrad Kayvon K Collins Natalie D ND Vasan Sandhya S Tucker Cynthia C Daye Sharon S Happi Christian Tientcha CT

Emerging microbes & infections 20240122 1

Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle an ...[more]

PMID: 38088796

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Project description:Annual outbreaks of Lassa fever have resulted in a public health threat in Nigeria and other endemic countries in Sub-Saharan Africa. While the Lassa Virus (LASV) is endemic in rodent populations, zoonotic spillover to humans causes annual outbreaks. This study reviewed the burden of Lassa fever (LF) in Nigeria between 2020 and 2023 and conducted a cross-sectional survey of Nigerians to evaluate their risk perceptions of LF. During the period under review, 28,780 suspected and 4,036 confirmed cases of LF were reported from 34 of the 37 states of Nigeria. These cases resulted in 762 deaths (a CFR of 18.9%). The overall case positivity rate was 14% (4,036/28,780), with more positive cases in 2020 (17.5%, n = 1,189/6,791). A total of 2,150 study participants were enrolled in the prospective cross-sectional study, with most of them (87.5%, n = 1,881/2,150) having previously heard of Lassa fever (LF). The numerical scoring system revealed that 35.43% (n = 762/1,881) of those aware of LF have poor knowledge of its preventive measures, route of transmission, and control measures. Approximately 6.84% (n = 147/2,150) of them were at a high risk of contracting LF, with 27.6% (n = 584/2,150) of study participants feeling concerned about contracting LF because of the presence of rodents in their immediate vicinity, occupational exposure to healthcare workers, and the probability of contamination of food by infected rodents without necessary food safety measures. Multivariable logistic regression analysis revealed that tertiary education was associated with an increased likelihood of better LF knowledge (OR: 17.32; 95% CI: 10.62, 28.26; p < 0.01) and a lower risk of contracting LF when compared to respondents with no formal education. In addition, study participants who reside in low-burden states have lower LF perception than those residents in high-LF-burden states (OR: 0.59; 95% CI: 0.38-0.91; p = 0.049). On the other hand, study participants with poor risk perception (knowledge) of LF had a higher likelihood (RR: 0.33; 95% CI: 0.20, 0.53; p < 0.01) of contracting LF when compared to those with good knowledge of LF. Similarly, those residents in low LF burden states were less likely (OR: 0.09; 95% CI: 0.05,0.17; p < 0.01) to contract LF when compared to those residents in high burden states. There is a need to improve LF diagnostics capacity, infection prevention and control measures, and implementation of the One Health approach to controlling LASV from animal reservoirs. In addition, public enlightenment campaigns to address fundamental knowledge gaps are crucial to mitigating the ongoing and future impact of LF in Nigeria.

Project description:Lassa virus is genetically diverse with several lineages circulating in West Africa. This study aimed at describing the sequence variability of Lassa virus across Nigeria and inferring its spatiotemporal evolution. We sequenced and isolated 77 Lassa virus strains from 16 Nigerian states. The final data set, including previous works, comprised metadata and sequences of 219 unique strains sampled between 1969 and 2018 in 22 states. Most of this data originated from Lassa fever patients diagnosed at Irrua Specialist Teaching Hospital, Edo State, Nigeria. The majority of sequences clustered with the main Nigerian lineages II and III, while a few sequences formed a new cluster related to Lassa virus strains from Hylomyscus pamfi Within lineages II and III, seven and five sublineages, respectively, were distinguishable. Phylogeographic analysis suggests an origin of lineage II in the southeastern part of the country around Ebonyi State and a main vector of dispersal toward the west across the Niger River, through Anambra, Kogi, Delta, and Edo into Ondo State. The frontline of virus dispersal appears to be in Ondo. Minor vectors are directed northeast toward Taraba and Adamawa and south toward Imo and Rivers. Lineage III might have spread from northern Plateau State into Kaduna, Nasarawa, Federal Capital Territory, and Bauchi. One sublineage moved south and crossed the Benue River into Benue State. This study provides a geographic mapping of lineages and phylogenetic clusters in Nigeria at a higher resolution. In addition, we estimated the direction and time frame of virus dispersal in the country.IMPORTANCE Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality rate of approximately 30% in Africa. Previous studies disclosed a geographical pattern in the distribution of Lassa virus strains and a westward movement of the virus across West Africa during evolution. Our study provides a deeper understanding of the geography of genetic lineages and sublineages of the virus in Nigeria. In addition, we modeled how the virus spread in the country. This knowledge allows us to predict into which geographical areas the virus might spread in the future and prioritize areas for Lassa fever surveillance. Our study not only aimed to generate Lassa virus sequences from across Nigeria but also to isolate and conserve the respective viruses for future research. Both isolates and sequences are important for the development and evaluation of medical countermeasures to treat and prevent Lassa fever, such as diagnostics, therapeutics, and vaccines.

Project description:BackgroundThere is limited epidemiological evidence on Lassa fever in pregnant women with acute gaps on prevalence, infection incidence, and risk factors. Such evidence would facilitate the design of therapeutic and vaccine trials and the design of control programs. Our study sought to address some of these gaps by estimating the seroprevalence and seroconversion risk of Lassa fever in pregnant women.Methodology/principal findingsWe conducted a prospective hospital-based cohort between February and December 2019 in Edo State, Southern Nigeria, enrolling pregnant women at antenatal clinic and following them up at delivery. Samples were evaluated for IgG antibodies against Lassa virus. The study demonstrates a seroprevalence of Lassa IgG antibodies of 49.6% and a seroconversion risk of 20.8%. Seropositivity was strongly correlated with rodent exposure around homes with an attributable risk proportion of 35%. Seroreversion was also seen with a seroreversion risk of 13.4%.Conclusions/significanceOur study suggests that 50% of pregnant women were at risk of Lassa infection and that 35.0% of infections might be preventable by avoiding rodent exposure and conditions which facilitate infestation and the risk of human-rodent contact. While the evidence on rodent exposure is subjective and further studies are needed to provide a better understanding of the avenues of human-rodent interaction; public health measures to decrease the risk of rodent infestation and the risk of spill over events may be beneficial. With an estimated seroconversion risk of 20.8%, our study suggests an appreciable risk of contracting Lassa fever during pregnancy and while most of these seroconversions may not be new infections, given the high risk of adverse outcomes in pregnancy, it supports the need for preventative and therapeutic options against Lassa fever in pregnancy. The occurrence of seroreversion in our study suggests that the prevalence obtained in this, and other cohorts may be an underestimate of the actual proportion of women of childbearing age who present at pregnancy with prior LASV exposure. Additionally, the occurrence of both seroconversion and seroreversion in this cohort suggests that these parameters would need to be considered for the development of Lassa vaccine efficacy, effectiveness, and utility models.

Project description:IntroductionOne of the unexpected outcomes of the COVID-19 pandemic was the relatively low levels of morbidity and mortality in Africa compared to the rest of the world. Nigeria, Africa's most populous nation, accounted for less than 0.01% of the global COVID-19 fatalities. The factors responsible for Nigeria's relatively low loss of life due to COVID-19 are unknown. Also, the correlates of protective immunity to SARS-CoV-2 and the impact of pre-existing immunity on the outcome of the COVID-19 pandemic in Africa are yet to be elucidated. Here, we evaluated the natural and vaccine-induced immune responses from vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria throughout the three waves of the COVID-19 pandemic in Nigeria. We also examined the pre-existing immune responses to SARS-CoV-2 from samples collected prior to the COVID-19 pandemic.MethodsWe used spike RBD and N- IgG antibody ELISA to measure binding antibody responses, SARS-CoV-2 pseudotype assay protocol expressing the spike protein of different variants (D614G, Delta, Beta, Omicron BA1) to measure neutralizing antibody responses and nucleoprotein (N) and spike (S1, S2) direct ex vivo interferon gamma (IFNγ) T cell ELISpot to measure T cell responses.ResultOur study demonstrated a similar magnitude of both binding (N-IgG (74% and 62%), S-RBD IgG (70% and 53%) and neutralizing (D614G (49% and 29%), Delta (56% and 47%), Beta (48% and 24%), Omicron BA1 (41% and 21%)) antibody responses from symptomatic and asymptomatic survivors in Nigeria. A similar magnitude was also seen among vaccinated participants. Interestingly, we revealed the presence of preexisting binding antibodies (N-IgG (60%) and S-RBD IgG (44%)) but no neutralizing antibodies from samples collected prior to the pandemic.DiscussionThese findings revealed that both vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria make similar magnitude of both binding and cross-reactive neutralizing antibody responses. It supported the presence of preexisting binding antibody responses among some Nigerians prior to the COVID-19 pandemic. Lastly, hybrid immunity and heterologous vaccine boosting induced the strongest binding and broadly neutralizing antibody responses compared to vaccine or infection-acquired immunity alone.

Dataset Information

Lassa virus in novel hosts: insights into the epidemiology of lassa virus infections in southern Nigeria.

Publications

Lassa virus in novel hosts: insights into the epidemiology of lassa virus infections in southern Nigeria.

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