SciCombinator

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Concept: Lassa fever

175

Poor quality housing is an infringement on the rights of all humans to a standard of living adequate for health. Among the many vulnerabilities of those without adequate shelter is the risk of disease spread by rodents and other pests. One such disease is Lassa fever, an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. Lassa virus is maintained in the rodent Mastomys natalensis, commonly known as the “multimammate rat,” which frequently invades the domestic environment, putting humans at risk of Lassa fever. The highest reported incidence of Lassa fever in the world is consistently in the Kenema District of Sierra Leone, a region that was at the center of Sierra Leone’s civil war in which tens of thousands of lives were lost and hundreds of thousands of dwellings destroyed. Despite the end of the war in 2002, most of Kenema’s population still lives in inadequate housing that puts them at risk of rodent invasion and Lassa fever. Furthermore, despite years of health education and village hygiene campaigns, the incidence of Lassa fever in Kenema District appears to be increasing. We focus on Lassa fever as a matter of human rights, proposing a strategy to improve housing quality, and discuss how housing equity has the potential to improve health equity and ultimately economic productivity in Sierra Leone. The manuscript is designed to spur discussion and action towards provision of housing and prevention of disease in one of the world’s most vulnerable populations.

Concepts: Epidemiology, Viral hemorrhagic fever, Lassa fever, Sierra Leone, Freetown, Kenema, Eastern Province, Sierra Leone, Kenema District

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Lassa virus (LASV) is endemic to parts of West Africa and causes highly fatal hemorrhagic fever. The multimammate rat (Mastomys natalensis) is the only known reservoir of LASV. Most human infections result from zoonotic transmission. The very diverse LASV genome has 4 major lineages associated with different geographic locations. We used reverse transcription PCR and resequencing microarrays to detect LASV in 41 of 214 samples from rodents captured at 8 locations in Sierra Leone. Phylogenetic analysis of partial sequences of nucleoprotein (NP), glycoprotein precursor (GPC), and polymerase (L) genes showed 5 separate clades within lineage IV of LASV in this country. The sequence diversity was higher than previously observed; mean diversity was 7.01% for nucleoprotein gene at the nucleotide level. These results may have major implications for designing diagnostic tests and therapeutic agents for LASV infections in Sierra Leone.

Concepts: DNA, Gene, Virus, RNA, Viral hemorrhagic fever, Lassa fever, Liberia, Sierra Leone

61

Sierra Leone in West Africa is in a Lassa fever-hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ≈500-700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%-40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%-70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus.

Concepts: Malaria, Yellow fever, Ribavirin, Fever, Viral diseases, Viral hemorrhagic fever, Lassa fever, Sierra Leone

29

Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions.

Concepts: Microbiology, Malaria, Africa, Pathogen, Fever, Viral hemorrhagic fever, Zoonosis, Lassa fever

26

The N terminus of arenavirus L protein contains an endonuclease presumably involved in “cap-snatching”. Here, we employed the Lassa virus replicon system to map other L protein sites that might be involved in this mechanism. Residues Phe-1979, Arg-2018, Phe-2071, Asp-2106, Trp-2173, Tyr-2179, Arg-2200, and Arg-2204 were important for viral mRNA synthesis, but dispensable for genome replication. Thus, the C terminus of L protein is involved in the mRNA synthesis process, potentially by mediating cap-binding.

Concepts: DNA, Protein, RNA, N-terminus, Lassa fever

18

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.

Concepts: Virus, Influenza, Ribavirin, Fever, West Africa, Viral hemorrhagic fever, Lassa fever, Sierra Leone

10

This paper argues that addressing the underlying structural drivers of disease vulnerability is essential for a ‘One Health’ approach to tackling zoonotic diseases in Africa. Through three case studies-trypanosomiasis in Zimbabwe, Ebola and Lassa fever in Sierra Leone and Rift Valley fever in Kenya-we show how political interests, commercial investments and conflict and securitization all generate patterns of vulnerability, reshaping the political ecology of disease landscapes, influencing traditional coping mechanisms and affecting health service provision and outbreak responses. A historical, political economy approach reveals patterns of ‘structural violence’ that reinforce inequalities and marginalization of certain groups, increasing disease risks. Addressing the politics of One Health requires analysing trade-offs and conflicts between interests and visions of the future. For all zoonotic diseases economic and political dimensions are ultimately critical and One Health approaches must engage with these factors, and not just end with an ‘anti-political’ focus on institutional and disciplinary collaboration.This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.

Concepts: HIV, Malaria, Brucellosis, Swine influenza, Zoonosis, Lassa fever, Zoonoses, Sierra Leone

9

This article explores the implications for human health of local interactions between disease, ecosystems and livelihoods. Five interdisciplinary case studies addressed zoonotic diseases in African settings: Rift Valley fever (RVF) in Kenya, human African trypanosomiasis in Zambia and Zimbabwe, Lassa fever in Sierra Leone and henipaviruses in Ghana. Each explored how ecological changes and human-ecosystem interactions affect pathogen dynamics and hence the likelihood of zoonotic spillover and transmission, and how socially differentiated peoples' interactions with ecosystems and animals affect their exposure to disease. Cross-case analysis highlights how these dynamics vary by ecosystem type, across a range from humid forest to semi-arid savannah; the significance of interacting temporal and spatial scales; and the importance of mosaic and patch dynamics. Ecosystem interactions and services central to different people’s livelihoods and well-being include pastoralism and agro-pastoralism, commercial and subsistence crop farming, hunting, collecting food, fuelwood and medicines, and cultural practices. There are synergies, but also tensions and trade-offs, between ecosystem changes that benefit livelihoods and affect disease. Understanding these can inform ‘One Health’ approaches towards managing ecosystems in ways that reduce disease risks and burdens.This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.

Concepts: Medicine, Agriculture, Malaria, Africa, Zoonosis, Lassa fever, Zoonoses, Sierra Leone

8

The recent emergence of Zaire ebolavirus in West Africa(1) has come as a surprise in a region more commonly known for its endemic Lassa fever, another viral hemorrhagic fever caused by an Old World arenavirus. Yet the region has seen previous ebolavirus activity (see map). In the mid-1990s, scientists discovered Côte d'Ivoire ebolavirus (now known as Taï Forest ebolavirus) as a cause of a single reported nonfatal case in a researcher who performed a necropsy on an infected chimpanzee. The episode initiated a major research investigation in and around the Taï Forest region - an effort that failed to identify . . .

Concepts: Ebola, Marburg virus, Viral hemorrhagic fever, Lassa fever

7

The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health.

Concepts: Immune system, Antibody, DNA, Protein, Chemistry, Ribavirin, Viral hemorrhagic fever, Lassa fever