#Nosocomial #outbreak of #Lassa fever in Conakry, #Guinea, 2022

 

Abstract

Background

Lassa fever (LF) is endemic in Guinea, with high seroprevalence in the forest region. However, clinical cases have been only anecdotally reported. In August 2022, a nosocomial outbreak occurred at a private clinic in the capital Conakry, an area previously considered low risk.

Methods

Suspected cases were confirmed by real-time RT-PCR within 24 hours. Viremia was monitored during hospitalization, and whole-genome sequencing was performed in-country within 13 days of outbreak detection. Outbreak investigation involved rodent testing in the home village of the suspected primary case.

Results

Six cases were laboratory-confirmed, five of which were healthcare workers of the clinic. The case fatality rate was 16.7%. Viral RNA remained detectable in blood of survivors for a median of 26 days (IQR 24-41) post disease onset. Epidemiological investigations identified a suspected primary case, who had died of a febrile disease compatible with Lassa fever, had contact with all secondary cases, and had a travel history from Kissidougou area. Three near-complete and one partial Lassa virus genomes were recovered from the secondary cases, which phylogenetically clustered with genomes from central Guinea. Consistent with a common transmission source, the four genomes were almost identical. Rodent testing revealed a new reservoir area in eastern-central Guinea.

Discussion

This outbreak highlights the vulnerability of healthcare settings in low-prevalence areas of West Africa to nosocomial Lassa virus transmission due to human mobility. Facilitated by capacity building programs for viral hemorrhagic fevers, rapid diagnosis, genomic analysis, and ecological assessment enabled an efficient outbreak response and control.

Source: 

Link: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiag229/8661158

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The virus entry #inhibitor ARN-75039 provides therapeutic #protection against #Lassa virus infection in guinea pigs

 

Abstract

Lassa virus (LASV), a member of the Arenaviridae family, causes Lassa fever. There are no vaccines available for prevention of Lassa fever, and the primary therapeutic for treatment (ribavirin) has questionable antiviral activity and no formal approval for use. Here, we evaluated ARN-75039, an orally bioavailable broad-spectrum mammarenavirus entry inhibitor, against LASV infection in outbred Hartley guinea pigs exposed to a guinea pig–adapted LASV. ARN-75039 was administered for 14 days either 3 or 7 days postexposure (dpe) to LASV. In the first two studies, once-daily dosing at 3 dpe provided protection against lethal infection. A third study with twice-daily dosing at 7 dpe also achieved protection. Both drug regimens offered 100% protection at the lowest tested doses of 3.75 mg/kg (once-daily administration) or 7.5 mg/kg (twice-daily administration). ARN-75039–treated animals exhibited minimal disease signs and undetectable viremia. These results suggest that ARN-75039, for which a phase 1 human clinical trial has now been completed, may offer robust protection against LASV infection.

Source: 

Link: https://www.science.org/doi/10.1126/scitranslmed.adx0938

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Post-discharge #sequelae of #Lassa fever #survivors in #Nigeria: an analysis of the LASCOPE prospective cohort

 

Summary

Background

Lassa fever is one of the most important viral haemorrhagic fevers, yet post-discharge sequelae remain inadequately characterised. Previous studies have been limited by small sample sizes and unsystematic assessments. We aimed to describe post-discharge sequelae in Lassa fever survivors and explore the effect of disease severity on sequelae patterns.

Methods

LASCOPE was a prospective study of patients with PCR-confirmed Lassa fever hospitalised at Federal Medical Centre Owo, Owo, Nigeria, between April 23, 2018, and Feb 17, 2023. All patients who provided informed consent were included, with no age restriction. Severe disease was defined as the presence of at least one of the following during the acute phase: National Early Warning Score version 2 score of 7 or higher, Kidney Disease Improving Global Outcomes stage 2 or higher, or Lassa virus PCR Ct value of less than 25. At hospital discharge, follow-up of survivors was planned for day 60 after admission, or before that, based on medical need. A systematic symptom assessment was done at each visit. The main outcome was clinical remission, defined as complete absence of symptoms. Other outcomes were post-discharge death, symptom incidence, and prevalence of symptoms over time. Subgroup analyses were performed by age group (children aged <18 years or adults aged ≥18 years) and disease severity (severe or not severe).

Findings

Of 882 survivors (median age 32 years [IQR 22–46], 459 [52%] female and 423 [48%] male), post-discharge data were available for 807 (91%), with a total of 2603 person-months of follow-up. For three of 807 survivors with post-discharge information, only the vital status was collected. 736 (91%) of 807 reached clinical remission, with a median time to clinical remission of 19 days (95% CI 16–23) post discharge. The most frequently reported symptoms were asthenia (158 [20%] of 804), headache (148 [18%]), and post-exertional malaise (123 [15%]). Hearing symptoms were reported by only 17 (2%) of 804 survivors, which was substantially lower than previous studies. Disease severity did not affect time to remission. Six (1%) survivors died after hospital discharge.

Interpretation

Patient-reported symptoms suggest good recovery with few hearing or neurosensory disorders in most survivors of Lassa fever. Future research would benefit from extended follow-up periods and standardised diagnostic assessments, including objective audiometry, to further characterise the full spectrum of post-Lassa fever complications.

Funding

Institut National de la Santé et de la Recherche Médicale, University of Oxford, EU, UK Department for International Development, Wellcome Trust, French Ministry of Foreign Affairs, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, and French National Research Institute for Sustainable Development.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00057-5/abstract?rss=yes

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#Lassa fever #symptomatology, viral dynamics, and host immune response (PREPARE): a prospective, observational cohort study in #Liberia

 

Summary

Background

Lassa virus (LASV) is a persistent threat to public health in west Africa and beyond. LASV is endemic in west Africa and each year it is responsible for an estimated 2·7 million infections, 23 700 hospitalisations, and 5000 deaths. With over 32 reported cases of Lassa fever imported into non-endemic countries—one-third of which were fatal—the importance of enhanced detection and management of Lassa fever extends beyond west Africa.

Methods

The prevalence, pathogenesis, and persistence (PREPARE) study was a prospective cohort study among patients admitted to two hospitals in a hyperendemic area of Liberia. Any patients aged 5 years or older with a febrile illness were eligible to enrol and be tested for Lassa fever. The study aimed to measure the prevalence of LASV infection and assess the signs and symptoms, LASV viral replication kinetics, and LASV-specific IgM and IgG responses longitudinally among adults and children with laboratory-confirmed Lassa fever.

Findings

From July 10, 2018, to Aug 12, 2024, a total of 435 participants were enrolled, including 362 admitted with a febrile illness and 73 who were directly admitted with clinical suspicion for Lassa fever. Lassa fever was diagnosed by plasma LASV RT-PCR in 41 (11%) of 362 febrile participants and 47 (64%) of 73 participants directly admitted with suspected Lassa fever, resulting in a total of 88 cases of confirmed Lassa fever. At entry, anorexia (71 [81%] of 88 vs 178 [51%] of 347), severe fatigue or weakness (63 [72%] vs 178 [51%]), and nausea or vomiting (39 [44%] vs 95 [27%]) were more likely to be reported by participants with Lassa fever than by participants who tested LASV RNA negative. Among the participants with Lassa fever, 11 (13%) of 88 died after admission. Mental status changes, seizures, acute kidney failure, hyperkalaemia, and metabolic acidosis were more frequent in patients with Lassa fever who died than in patients who survived. Median cycle threshold values at study entry for glycoprotein complex gene (GPC) or polymerase gene (L) were lower in those who died (GPC cycle threshold 22·4 [IQR 20·0–27·9]; L cycle threshold 21·7 [19·0–27·7]) than in those who survived (GPC cycle threshold 31·5 [28·0–33·9]; L cycle threshold 32·3 [28·0–33·9]). Among the 70 participants with Lassa fever who consented to longitudinal follow-up through their hospitalisation, seven died and these participants tended to have lower cycle threshold values and lower IgM and IgG LASV responses compared with survivors.

Interpretation

In a region of Liberia where it is endemic, Lassa fever is a prevalent cause of morbidity and mortality. Several symptoms were more likely in those with Lassa fever but overlap with those caused by other common infectious diseases. Compared with survivors, those who died during hospitalisation for Lassa fever tended to have evidence of organ dysfunction along with higher viral loads at study entry and during follow-up and lower antibody levels during their illness, suggesting a muted humoral immune response might be a factor in the development of severe Lassa fever.

Funding

US National Institute of Allergy and Infectious Diseases and National Institutes of Health.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00725-X/abstract?rss=yes

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#Serological evidence of concurrent #Lassa virus and #SARS-CoV-2 #exposure in #Ghana- a cross-sectional study

 

Abstract

Background

The COVID-19 pandemic has exposed vulnerabilities in infectious disease surveillance, especially in West Africa where endemic viruses including Lassa fever persist. The overlapping clinical symptoms of these two infections create diagnostic challenges and the possibility of undetected co-infections.

Methods

A retrospective cross-sectional study was conducted using archived serum samples from a nationwide SARS-CoV-2 seroprevalence survey in Ghana. 434 samples across six regions were tested for SARS-CoV-2 total antibodies (IgG/IgM) using the WANTAI ELISA kit and Lassa virus IgG using ReLASV Pan-Lassa-NP-IgG ELISA.

Results

SARS-CoV-2 antibody prevalence was 64.29% (n = 279) and Lassa virus IgG prevalence was 20.28% (n = 88). Of the cohort of subjects who were seropositive for SARS-CoV-2, 20.79% were also seropositive for LASV IgG. Multivariate analysis revealed household size as a strong risk factor of dual exposure. Individuals from medium-sized households (4–6 persons) (aOR = 8.78, 95% CI: 1.18–65.56, p = 0.034) and large households (≥ 7 persons) (aOR = 12.90, 95% CI: 1.99–83.40, p = 0.007) had significantly increased odds of dual seropositivity compared to small households. Regional variations were observed, with Greater Accra showing significantly lower odds of dual seropositivity (aOR = 0.13, 95% CI: 0.03–0.51, p = 0.004) compared to Ashanti Region.

Conclusion

This study provides serological evidence of SARS-CoV-2 and Lassa virus concurrent exposure in Ghana during the COVID-19 pandemic. This finding suggests large household size as a key driver of dual viral exposure and calls for integrated surveillance systems and targeted interventions in large household settings to reduce concurrent transmission of viruses with pandemic potential.

Source: 

Link: https://link.springer.com/article/10.1186/s12879-025-12385-1

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Safety, tolerability, and immunogenicity of INO-4500, a synthetic #DNA-based #vaccine against #Lassa virus, in a phase 1b clinical trial in healthy Ghanaian adults

 

Abstract

Background: 

Lassa fever (LF) is an acute viral hemorrhagic illness endemic to West Africa, with no licensed vaccines or targeted treatments available, highlighting a critical gap in global health preparedness. T cell-mediated immunity plays a central role in viral control and survival. Synthetic DNA vaccines offer a promising strategy to induce both humoral and cellular immunity against LF.

Methods: 

A Phase 1b, randomized, double-blind, placebo-controlled trial was conducted to assess the safety, tolerability, and immunogenicity of INO-4500, a DNA vaccine encoding the Lassa virus (Josiah strain) glycoprotein precursor (GPC). A total of 220 healthy adults were randomized to receive either 1 mg or 2 mg of INO-4500 (intervention), or placebo, administered intradermally (ID) followed by electroporation (EP) at Day 0 and Week 4. Safety was evaluated through Week 48. Primary immunogenicity endpoints included humoral and cellular immune responses at multiple timepoints post-vaccination.

Results: 

INO-4500 was well tolerated, with no Grade 3 or higher treatment-emergent adverse events (TEAEs) deemed to be related to the intervention; 88.6% of all TEAEs were Grade 1. No cases of attributable hearing loss were reported. INO-4500 groups demonstrated statistically significant increases in Lassa virus GPC-specific binding antibodies at Weeks 6 and 12 compared to placebo, with the 2 mg group eliciting the strongest responses. T cell responses remained elevated above baseline through Week 48 in both INO-4500 groups, indicating durable cellular immunity.

Conclusions: 

DNA vaccine INO-4500 was well tolerated and elicited durable humoral and cellular immune responses in healthy adults. These findings support further clinical development of INO-4500 as a potential preventive vaccine to reduce LF-associated morbidity and mortality in endemic regions.

Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04093076

Source: Frontiers in Immunology, https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1658549/full

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#Safety and Immunogenicity of an rVSV #Lassa Fever #Vaccine Candidate

 

Abstract

Background

No vaccine is currently available for Lassa fever, a viral hemorrhagic disease that is estimated to cause thousands of deaths each year in western Africa. A replication-competent recombinant vesicular stomatitis virus–vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex, rVSVΔG-LASV-GPC, has been developed, but data on its safety and immunogenicity are limited.

Methods

In this phase 1, double-blind trial conducted in the United States and Liberia, we randomly assigned healthy adults (18 to 50 years of age) to receive rVSVΔG-LASV-GPC or placebo intramuscularly. Participants received a single vaccine dose of 2×104 plaque-forming units (PFU), 2×105 PFU, 2×106 PFU, or 2×107 PFU or placebo or received two vaccine doses of 2×107 PFU or placebo, within a window of 6 to 20 weeks. The side-effect profile was assessed according to the incidence of solicited and unsolicited adverse events (primary end point). Because Lassa fever can cause sensorineural hearing loss, hearing acuity was measured before and after the injection. Secondary end points were levels of binding antibodies against LASV glycoprotein, neutralizing antibodies, and vaccine vector–derived viral RNA and PFU in plasma, urine, and saliva.

Results

A total of 114 adults were enrolled. No serious vaccine-related adverse events were reported. The vaccine caused minimal local reactions and dose-dependent, mild-to-severe early-onset systemic reactogenicity events that were transient. No hearing loss was detected. All doses induced robust long-lasting cellular and humoral (binding and neutralizing) responses that cross-reacted against common LASV lineages. No infectious vaccine virus particles were found in plasma, urine, or saliva.

Conclusions

The rVSVΔG-LASV-GPC vaccine resulted in transient local and systemic reactogenicity events but no hearing loss or serious adverse events. The vaccine had immunogenicity over a wide dose range in healthy adults in the United States and Liberia. (Funded by the Coalition for Epidemic Preparedness Innovations and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04794218; Pan African Clinical Trials Registry number, PACTR2021106625781067.)

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2501073?query=TOC

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#Lassa Virus #Infection of Primary #Human #Airway Epithelial Cells

Abstract

Lassa mammarenavirus (LASV), a member of the family Arenaviridae, is a highly pathogenic virus capable of causing severe systemic infections in humans. The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure to virus-containing aerosols from rodent excretions. To better understand the molecular mechanisms underlying LASV replication in the respiratory tract, we utilized differentiated primary human airway epithelial cells (HAECs) grown under air–liquid interface conditions, closely mimicking the bronchial epithelium in vivo. Our findings demonstrate that HAECs are permissive to LASV infection and support productive virus replication. While LASV entry into polarized HAECs occurred through both apical and basolateral surfaces, progeny virus particles were predominantly released from the apical surface, consistent with an intrinsic apical localization of the envelope glycoprotein GP. This suggests that apical virus shedding from infected bronchial epithelia may facilitate LASV transmission via airway secretions. Notably, limited basolateral release at later stages of infection was associated with LASV-induced rearrangement of the actin cytoskeleton, resulting in compromised epithelial barrier integrity. Finally, we demonstrate that LASV-infected HAECs exhibited a pronounced type III interferon response. A detailed understanding of LASV replication and host epithelial responses in the respiratory tract could facilitate the development of targeted future therapeutics.

Source: Viruses, https://www.mdpi.com/1999-4915/17/5/592

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Coadministration of #ribavirin and #arenaviral entry #inhibitor LHF-535 enhances antiviral benefit against authentic #Lassa virus

{Excerpt}

Highlights

• A new strain of Lassa virus (LASV) was successfully isolated and characterized.

• The combination of ribavirin and LHF-535 has been demonstrated to exhibit synergistic effects in inhibiting LASV.

• The findings provide new directions for the development of antiviral drugs and vaccines for Lassa fever.

Dear Editor,

Lassa virus (LASV) is the causative agent of the acute viral hemorrhagic Lassa fever (LF), which is classified into Mammarenavirus within the Arenaviridae family, with a single-stranded, negative-sense, bi-segmented RNA genome. Due to its high pathogenicity and lethality, LASV is considered as a priority threat to public health, with an estimated cases of 300,000 infections and 5,000 deaths annually. LASV was first isolated and described as a clinical entity in 1969 in Lassa, Nigeria (Garry, 2023). LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages, with each lineage predominately localized in specific countries. Although the research on LF has been carried out for decades since the pathogen first characterized, there is no approved antiviral drugs or vaccines for clinical use against LASV to date (Grant et al., 2023). One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4 (BSL-4) facilities. In this letter, we describe isolation, and characterization of the LASV from the clinical samples. And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility, aiming to investigate new therapeutic strategies for LASV infection.

(...)

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000380?via%3Dihub

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#UK, #England: #Lassa #fever contact #tracing underway

The UK Health Security Agency has been informed under the International Health Regulations that an individual travelled to England from Nigeria while they were unwell with Lassa fever at the end of February. The individual returned to Nigeria where they were diagnosed.

We are now working to identify people who were in contact with the affected individual while they were in the country.

Lassa fever does not spread easily between people and the overall risk to the public is very low. If you have not been contacted by UKHSA then you are very unlikely to have had any exposure to Lassa fever and do not need to take action.

Lassa fever causes acute infections which can range from very mild symptoms through to a severe viral haemorrhagic fever. People usually become infected with Lassa virus through exposure to food or household items contaminated with urine or faeces of infected rats – present in some West African countries where the disease is endemic. The virus can also be spread between people through contact with infectious bodily fluids.

Dr Meera Chand, Deputy Director at the UK Health Security Agency, said:

''Our Health Protection Teams are working at pace to get in touch with people who were in contact with this individual while they were in England, to ensure they seek appropriate medical care and testing should they develop any symptoms. The infection does not spread easily between people, and the overall risk to the UK population is very low.''

Source: UK Health Security Agency, https://www.gov.uk/government/news/lassa-fever-contact-tracing-underway

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