Combating Lassa Fever in West African Sub-Region: Progress, Challenges, and Future Perspectives

Aloke, Chinyere; Obasi, Nwogo Ajuka; Aja, P. M.; Emelike, Chinedum Uche; Egwu, Chinedu Ogbonnia; Jeje, Olamide; Edeogu, Chuks Oswald; Onisuru, Olalekan Olugbenga; Orji, O.U.; Achilonu, Ikechukwu

doi:10.3390/v15010146

Cited by 15 publications

(13 citation statements)

References 162 publications

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“…First documented in 1969, Lassa fever is caused by the Lassa virus (LASV), transmitted by the multimammate rat Mastomys natalensis , and remains a threat in West Africa [ 206 , 207 ]. Illustrating the difficulties of obtaining pathogen nucleic acids from clinical samples, direct sequencing of clinical and biological samples yielded poor recovery LASV material, despite extensive depletion of carrier and host RNA, albeit sufficient recovery of Ebola virus (EBOV) sequences was observed [ 208 ].…”

Section: Biosurveillance and Emerging Viral Infectious Diseasesmentioning

confidence: 99%

Hybrid-Capture Target Enrichment in Human Pathogens: Identification, Evolution, Biosurveillance, and Genomic Epidemiology

Quek,

2024

Pathogens

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High-throughput sequencing (HTS) has revolutionised the field of pathogen genomics, enabling the direct recovery of pathogen genomes from clinical and environmental samples. However, pathogen nucleic acids are often overwhelmed by those of the host, requiring deep metagenomic sequencing to recover sufficient sequences for downstream analyses (e.g., identification and genome characterisation). To circumvent this, hybrid-capture target enrichment (HC) is able to enrich pathogen nucleic acids across multiple scales of divergences and taxa, depending on the panel used. In this review, we outline the applications of HC in human pathogens—bacteria, fungi, parasites and viruses—including identification, genomic epidemiology, antimicrobial resistance genotyping, and evolution. Importantly, we explored the applicability of HC to clinical metagenomics, which ultimately requires more work before it is a reliable and accurate tool for clinical diagnosis. Relatedly, the utility of HC was exemplified by COVID-19, which was used as a case study to illustrate the maturity of HC for recovering pathogen sequences. As we unravel the origins of COVID-19, zoonoses remain more relevant than ever. Therefore, the role of HC in biosurveillance studies is also highlighted in this review, which is critical in preparing us for the next pandemic. We also found that while HC is a popular tool to study viruses, it remains underutilised in parasites and fungi and, to a lesser extent, bacteria. Finally, weevaluated the future of HC with respect to bait design in the eukaryotic groups and the prospect of combining HC with long-read HTS.

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Section: Biosurveillance and Emerging Viral Infectious Diseasesmentioning

confidence: 99%

Hybrid-Capture Target Enrichment in Human Pathogens: Identification, Evolution, Biosurveillance, and Genomic Epidemiology

Quek,

2024

Pathogens

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“…Arenaviruses cause zoonotic hemorrhagic diseases via rodents and include Lassa fever and Machupo viruses ( 13 ). Rodent-to-human transmission occurs through contact with urine, feces, and saliva in contaminated food, aerosolized particles, and epidermal barrier lesions.…”

Section: Virusesmentioning

confidence: 99%

“…Human-to-human transmission occurs through direct contact with infectious body fluids and contaminated fomites ( 14 ). Lassa fever is an arenavirus endemic to Africa and transmitted by the Mastomys natalensis mouse ( 13 ). Systemic manifestations include fever, exudative pharyngitis, proteinuria, emesis, sensorineural hearing loss, and other neurologic complications.…”

Section: Virusesmentioning

confidence: 99%

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Ophthalmic implications of biological threat agents according to the chemical, biological, radiological, nuclear, and explosives framework

Curran,

Devine,

Hartley

et al. 2024

Front. Med.

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As technology continues to evolve, the possibility for a wide range of dangers to people, organizations, and countries escalate globally. The United States federal government classifies types of threats with the capability of inflicting mass casualties and societal disruption as Chemical, Biological, Radiological, Nuclear, and Energetics/Explosives (CBRNE). Such incidents encompass accidental and intentional events ranging from weapons of mass destruction and bioterrorism to fires or spills involving hazardous or radiologic material. All of these have the capacity to inflict death or severe physical, neurological, and/or sensorial disabilities if injuries are not diagnosed and treated in a timely manner. Ophthalmic injury can provide important insight into understanding and treating patients impacted by CBRNE agents; however, improper ophthalmic management can result in suboptimal patient outcomes. This review specifically addresses the biological agents the Center for Disease Control and Prevention (CDC) deems to have the greatest capacity for bioterrorism. CBRNE biological agents, encompassing pathogens and organic toxins, are further subdivided into categories A, B, and C according to their national security threat level. In our compendium of these biological agents, we address their respective CDC category, systemic and ophthalmic manifestations, route of transmission and personal protective equipment considerations as well as pertinent vaccination and treatment guidelines.

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“…LF was first described in humans in the 1950s, with the virus later identified in 1969 (5). It is endemic in Benin, Ghana, Guinea, Liberia, Mali, Sierra Leone, and Nigeria, and transmission is likely in other West African countries where Mastomys rodent reservoir hosts are present (6). Transmission to humans occurs through contact with infected animals or direct contact, inhalation, or ingestion of their excreta.…”

Section: Introductionmentioning

confidence: 99%

Lassa fever outbreaks, mathematical models, and disease parameters: a systematic review and meta-analysis

Doohan,

Jorgensen,

Naidoo

et al. 2024

Preprint

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BackgroundLassa fever, caused by Lassa virus (LASV), poses a significant public health threat in West Africa. Understanding the epidemiological parameters and transmission dynamics of LASV is crucial for informing evidence-based interventions and outbreak response strategies.MethodsWe conducted a systematic review (PROSPERO CRD42023393345) to compile and analyse key epidemiological parameters, mathematical models, and past outbreaks of LASV. Data were double extracted from published literature, focusing on past outbreaks, seroprevalence, transmissibility, epidemiological delays, and disease severity.FindingsWe found 157 publications meeting our inclusion criteria and extracted 374 relevant parameter estimates. Although LASV is endemic in West Africa, spatiotemporal coverage of recent seroprevalence estimates, ranging from 0.06% to 35%, was poor. Highlighting the uncertainty in LASV risk spatially. Similarly, only two basic reproduction number estimates at 1.13 and 1.19 were available. We estimated a pooled total random effect case fatality ratio of 33.1% (95% CI: 25.7 – 41.5, I2= 94%) and found potential variation in severity by geographic regions typically associated with specific LASV lineages. We estimated a pooled total random effect mean symptom-onset-to-hospital-admission delay of 8.3 days (95% CI: 7.4 – 9.3, I2 = 92%), but other epidemiological delays were poorly characterised.InterpretationOur findings highlight the relative lack of empirical LASV parameter estimates despite its high severity. Improved surveillance to capture mild cases and approaches that integrate rodent populations are needed to better understand LASV transmission dynamics. Addressing these gaps is essential for developing accurate mathematical models and informing evidence-based interventions to mitigate the impact of Lassa fever on public health in endemic regions.FundingUK Medical Research Council, National Institute for Health and Care Research, Academy of Medical Sciences, Wellcome, UK Department for Business, Energy, and Industrial Strategy, British Heart Foundation, Diabetes UK, Schmidt Foundation, Community Jameel, Royal Society, and Imperial College London.Research in ContextEvidence before this studyWe searched PubMed up to August 2, 2023 for ((lassa fever) or (lassa virus)) and (epidemiology or outbreak or (models not image) or transmissibility or severity or delays or (risk factors) or (mutation rate) or seroprevalence). We found ten systematic reviews. Three on ribavirin as a Lassa fever treatment, two on Lassa virus (LASV) vaccine candidates, and one each on historical importations of Lassa fever cases from West Africa to non-endemic countries, clinical characteristics for protocol development, and Lassa fever in pregnancy. Two systematically reviewed epidemiological parameters. One on basic reproduction number estimates which ranged from 1.1 to 1.8 for human-to-human and 1.5 to 1.7 for rodent-to-rodent transmission. However, no meta-analyses were conducted. The other focused on LASV infection case fatality ratios (CFRs): 29.7% (22.3–37.5) in humans and prevalence: 8.7% (95% confidence interval: 6.8– 10.8) in humans, 3.2% (1.9–4.6) in rodents, and 0.7% (0.0–2.3) in other mammals. There were no systematic reviews on LASV transmission models.Added value of this studyWe provide a comprehensive overview of published outbreaks, transmission models and epidemiological parameters for LASV. We highlight the sparsity of key epidemiological parameter estimates such as the serial interval or generation time. The discrepancy between the high overall severity and the high seroprevalence in the general population suggests a high proportion of infections are asymptomatic or only result in mild disease. Therefore, current surveillance systems may need refining to better characterise LASV transmission dynamics.Implications of all the available evidenceEpidemiological models are useful tools for real-time analysis of outbreaks, assessing epidemic trajectories and the impact of interventions. Our study is a useful basis to inform future LASV models, but highlights uncertainties and knowledge gaps that need to be filled in LASV transmission and natural history. Future LASV studies will benefit from integrating human and rodent reservoir surveillance.

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Combating Lassa Fever in West African Sub-Region: Progress, Challenges, and Future Perspectives

Cited by 15 publications

References 162 publications

Hybrid-Capture Target Enrichment in Human Pathogens: Identification, Evolution, Biosurveillance, and Genomic Epidemiology

Hybrid-Capture Target Enrichment in Human Pathogens: Identification, Evolution, Biosurveillance, and Genomic Epidemiology

Ophthalmic implications of biological threat agents according to the chemical, biological, radiological, nuclear, and explosives framework

Lassa fever outbreaks, mathematical models, and disease parameters: a systematic review and meta-analysis

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