The black rat (Rattus rattus) is a globally invasive species that has been widely introduced across Africa. Within its invasive range in West Africa, R. rattus may compete with the native rodent ...Mastomys natalensis, the primary reservoir host of Lassa virus, a zoonotic pathogen that kills thousands annually. Here, we use rodent trapping data from Sierra Leone and Guinea to show that R. rattus presence reduces M. natalensis density within the human dwellings where Lassa virus exposure is most likely to occur. Further, we integrate infection data from M. natalensis to demonstrate that Lassa virus zoonotic spillover risk is lower at sites with R. rattus. While non-native species can have numerous negative effects on ecosystems, our results suggest that R. rattus invasion has the indirect benefit of decreasing zoonotic spillover of an endemic pathogen, with important implications for invasive species control across West Africa.
Lassa fever (LF) is a devastating viral disease prevalent in West Africa. Efforts to take on this public health crisis have been hindered by lack of infrastructure and rapid field deployable ...diagnosis in areas where the disease is prevalent. Recent capacity building at the Kenema Government Hospital Lassa Fever Ward (KGH LFW) in Sierra Leone has lead to a major turning point in the diagnosis, treatment and study of LF. Herein we present the first comprehensive rapid diagnosis and real time characterization of an acute hemorrhagic LF case at KGH LFW. This case report focuses on a third trimester pregnant Sierra Leonean woman from the historically non-endemic Northern district of Tonkolili who survived the illness despite fetal demise. Employed in this study were newly developed recombinant LASV Antigen Rapid Test cassettes and dipstick lateral flow immunoassays (LFI) that enabled the diagnosis of LF within twenty minutes of sample collection. Deregulation of overall homeostasis, significant hepatic and renal system involvement, and immunity profiles were extensively characterized during the course of hospitalization. Rapid diagnosis, prompt treatment with a full course of intravenous (IV) ribavirin, IV fluids management, and real time monitoring of clinical parameters resulted in a positive maternal outcome despite admission to the LFW seven days post onset of symptoms, fetal demise, and a natural still birth delivery. These studies solidify the growing rapid diagnostic, treatment, and surveillance capabilities at the KGH LF Laboratory, and the potential to significantly improve the current high mortality rate caused by LF. As a result of the growing capacity, we were also able to isolate Lassa virus (LASV) RNA from the patient and perform Sanger sequencing where we found significant genetic divergence from commonly circulating Sierra Leonean strains, showing potential for the discovery of a newly emerged LASV strain with expanded geographic distribution. Furthermore, recent emergence of LF cases in Northern Sierra Leone highlights the need for superior diagnostics to aid in the monitoring of LASV strain divergence with potentially increased geographic expansion.
The spread of Lassa virus (LASV) in Guinea, Liberia and Sierra Leone, which together are named the Mano River Union (MRU) area, was examined phylogeographically. To provide a reliable evolutionary ...scenario, new rodent-derived, whole LASV sequences were included. These were generated by metatranscriptomic next-generation sequencing from rodents sampled between 2003 and 2020 in 21 localities of Guinea and Sierra Leone. An analysis was performed using BEAST to perform continuous phylogeographic inference and EvoLaps v36 to visualize spatio-temporal spread. LASV was identified as expected in its primary host reservoir, the Natal multimammate mouse (
), and also in two Guinean multimammate mice (
) in northern Sierra Leone and two rusty-bellied brush-furred mice (
) in southern Sierra Leone. This finding is consistent with the latter two species being secondary host reservoirs. The strains in these three species were very closely related in LASV lineage IV. Phylogenetic analysis indicated that the most recent common ancestor of lineage IV existed 316-374 years ago and revealed distinct, well-supported clades from Sierra Leone (Bo, Kabala and Kenema), Guinea (Faranah, Kissidougou-Guekedou and Macenta) and Liberia (Phebe-Ganta). The phylogeographic scenario suggests southern Guinea as the point of origin of LASV in the MRU area, with subsequent spread to towards Mali, Liberia and Sierra Leone at a mean speed of 1.6 to 1.1 km/year.
Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory ...characterisation of serological, biochemical and molecular aspects of the disease imported by infected individuals from Western Africa to the United States, Canada, Europe, Japan and Israel. Our report presents the first comprehensive real time diagnosis and characterization of a severe, hemorrhagic Lassa fever case in a Sierra Leonean individual admitted to the Kenema Government Hospital Lassa Fever Ward. Fever, malaise, unresponsiveness to anti-malarial and antibiotic drugs, followed by worsening symptoms and onset of haemorrhaging prompted medical officials to suspect Lassa fever. A recombinant Lassa virus protein based diagnostic was employed in diagnosing Lassa fever upon admission. This patient experienced a severe case of Lassa hemorrhagic fever with dysregulation of overall homeostasis, significant liver and renal system involvement, the interplay of pro- and anti-inflammatory cytokines during the course of hospitalization and an eventual successful outcome. These studies provide new insights into the pathophysiology and management of this viral illness and outline the improved infrastructure, research and real-time diagnostic capabilities within LASV endemic areas.
Ebola virus (EBOV) is a negative-strand RNA virus that replicates in the cytoplasm and causes an often-fatal hemorrhagic fever. EBOV, like other viruses, can reportedly encode its own microRNAs ...(miRNAs) to subvert host immune defenses. miRNAs are short noncoding RNAs that can regulate gene expression by hybridizing to multiple mRNAs, and viral miRNAs can enhance viral replication and infectivity by regulating host or viral genes. To date, only one EBOV miRNA has been examined in human infection. Here, we assayed mouse, rhesus macaque, cynomolgus macaque, and human samples infected with three EBOV variants for twelve computationally predicted viral miRNAs using RT-qPCR. Ten miRNAs aligned to EBOV variants and were detectable in the four species during disease with several viral miRNAs showing presymptomatic amplification in animal models. miRNA abundances in both the mouse and nonhuman primate models mirrored the human cohort, with miR-1-5p, miR-1-3p, and miR-T3-3p consistently at the highest levels. These striking similarities in the most abundant miRNAs during infection with different EBOV variants and hosts indicate that these miRNAs are potential valuable diagnostic markers and key effectors of EBOV pathogenesis.
During the mid-transmission period of the Ebola virus disease (EVD) outbreak in Sierra Leone, a 19-year-old pregnant woman, who was a petty trader in a health facility in Freetown, noticing no fetal ...movement for the past 3 days, reported to a health facility. Medical history and laboratory testing showed no abnormalities except that she was positive for sickle cell. She was not known to any surveillance team of having any epidemiological link to EVD case. She was induced with oral medications as well as IV infusion. EVD test showed that the fetus was positive to EVD with a high threshold value of 21, while the woman was negative for EVD with a threshold value of 42. The woman was positive to EVD IgG but negative to EVD IgM by ELISA technique. This is a rare EVD case in the period of medium transmission. We conclude that the woman may have come into contact with a low dose of virus not enough to cause a full blown EVD and that her immune system was able to stop the virus from further replication.
Community transmission of COVID-19 is ongoing in the majority of countries in sub-Saharan Africa (SSA), threatening, as elsewhere, the capacity of national healthcare systems (HCS) in low- and ...middle-income countries (LMIC) 1,2. In April, the WHO reported less than 2000 ventilators in 43, and only 5000 intensive care unit (ICU) beds in 41 African countries, respectively 1. While the manual is a resourceful compilation of highly useful and practical information 15, several passages seem distinctly out of touch with the realities lived in remote areas in LMIC, often near impossible to implement: “Use designated portable X-ray equipment and other important diagnostic equipment” (p.4); “Community facilities (e.g. stadiums, gymnasiums, hotels) with access to rapid health advice (i.e. adjacent COVID-19 designated health post/EMT-type 1, telemedicine)” (p. 8); “Mass critical care (e.g. open ICU for cohorted patients)” p.10; “Categorization of patients with severe acute respiratory infection (Chest imaging (radiograph, CT scan, lung ultrasound)”; or any significant “Surge capacity” p52. Following the governmental proposal to adapt existing infrastructure into COVID-19 treatment centers; at Masanga Hospital, this translated into the re-modelling of a pre-existing eye care building to receive COVID-19 cases with severe disease based on several key characteristics: large building size; location distant from the main hospital; proximity to a separate hospital gate; as well as the number of windows allowing for ample natural ventilation.
In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development's (USAID) Emerging ...Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security.
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