ABSTRACT
The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT.
Subject(s)
Genome, Viral , Lassa Fever/virology , Lassa virus/genetics , RNA, Viral/genetics , Africa, Western/epidemiology , Animals , Biological Evolution , Disease Reservoirs , Ebolavirus/genetics , Genetic Variation , Glycoproteins/genetics , Hemorrhagic Fever, Ebola/virology , Humans , Lassa Fever/epidemiology , Lassa Fever/transmission , Lassa virus/classification , Lassa virus/physiology , Murinae/genetics , Mutation , Nigeria/epidemiology , Viral Proteins/genetics , Zoonoses/epidemiology , Zoonoses/virologyABSTRACT
The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission.
Subject(s)
Ebolavirus/genetics , Ebolavirus/isolation & purification , Genome, Viral , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/virology , Mutation , Biological Evolution , Disease Outbreaks , Ebolavirus/classification , Hemorrhagic Fever, Ebola/transmission , Humans , Sierra Leone/epidemiology , Specimen HandlingABSTRACT
We note the reemergence of human monkeypox in Sierra Leone following a 44-year absence of reported disease. The persons affected were an 11-month-old boy and, several years later, a 35-year-old man. The reappearance of monkeypox in this country suggests a need for renewed vigilance and awareness of the disease and its manifestations.
Subject(s)
Communicable Diseases, Emerging/diagnosis , Communicable Diseases, Emerging/epidemiology , Mpox (monkeypox)/diagnosis , Mpox (monkeypox)/epidemiology , Adult , Communicable Diseases, Emerging/virology , Disease Notification , Humans , Infant , Male , Mpox (monkeypox)/virology , Public Health Surveillance , Sentinel Surveillance , Sierra Leone/epidemiologyABSTRACT
BACKGROUND: Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014. METHODS: We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase-polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients. RESULTS: Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness (in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient. CONCLUSIONS: The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.).
Subject(s)
Ebolavirus/genetics , Epidemics , Hemorrhagic Fever, Ebola/epidemiology , Abdominal Pain , Adult , Animals , Diarrhea , Ebolavirus/isolation & purification , Female , Fever , Hemorrhagic Fever, Ebola/complications , Hemorrhagic Fever, Ebola/therapy , Hemorrhagic Fever, Ebola/virology , Humans , Male , Middle Aged , Mortality , Reverse Transcriptase Polymerase Chain Reaction , Sierra Leone/epidemiology , Viral Load , VomitingABSTRACT
The current Ebola outbreak in West Africa has affected more people than all previous outbreaks combined. The current diagnostic method of choice, quantitative polymerase chain reaction, requires specialized conditions as well as specially trained technicians. Insufficient testing capacity has extended the time from sample collection to results. These delays have led to further delays in the transfer and treatment to Ebola Treatment Units. A sensitive and specific point-of-care device that could be used reliably in low-resource settings by healthcare workers with minimal training would increase the efficiency of triage and appropriate transfer of care. This article describes a study designed to validate the sensitivity and specificity of the ReEBOVTM Rapid Diagnostic Test using venous whole blood and capillary blood obtained via fingerprick. We present the scientific and clinical rationale for the decisions made in the design of a diagnostic validation study to be conducted in an outbreak setting. The multi-site strategy greatly complicated implementation. In addition, a decrease in cases in one geographic area along with a concomitant increase in other areas made site selection challenging. Initiation of clinical trials during rapidly evolving outbreaks requires significant cooperation on a national level between research teams implementing studies and clinical care providers. Coordination and streamlining of approval process are essential if trials are to be implemented in a timely fashion.
Subject(s)
Antigens, Viral/analysis , Ebolavirus/immunology , Hemorrhagic Fever, Ebola/diagnosis , Point-of-Care Systems , Reagent Kits, Diagnostic , Research Design , Validation Studies as Topic , Africa, Western/epidemiology , Disease Outbreaks , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/virology , Humans , Sensitivity and SpecificityABSTRACT
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.
Subject(s)
Genetic Variation , Lassa Fever/epidemiology , Lassa Fever/virology , Lassa virus/classification , Lassa virus/genetics , Phylogeography , Animals , Genes, Viral , Genome, Viral , Genotype , Geography , Lassa Fever/transmission , Oligonucleotide Array Sequence Analysis , Phylogeny , Rats , Sierra Leone/epidemiologyABSTRACT
Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.
Subject(s)
Lassa Fever , Humans , Lassa Fever/genetics , Lassa Fever/diagnosis , Lassa Fever/epidemiology , Genome-Wide Association Study , Seroepidemiologic Studies , Lassa virus/genetics , Fever , Human GeneticsABSTRACT
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.
Subject(s)
Health Promotion/methods , Health Status Disparities , Housing/standards , Lassa Fever/epidemiology , Africa, Western/epidemiology , Animals , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Human Rights/standards , Humans , Lassa Fever/transmission , Lassa virus/isolation & purification , Public Health/methods , Rats , Sierra Leone/epidemiology , WarfareABSTRACT
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.
Subject(s)
Immunoassay , Lassa Fever , Lassa virus/genetics , Pregnancy Complications, Infectious/virology , Ribavirin/administration & dosage , Antibodies, Viral/analysis , Antibodies, Viral/immunology , Antigens, Viral/analysis , Antigens, Viral/immunology , Case-Control Studies , Cytokines/analysis , Cytokines/biosynthesis , Female , Fetal Death , Genetic Variation , Humans , Injections, Intravenous , Lassa Fever/diagnosis , Lassa Fever/drug therapy , Lassa Fever/epidemiology , Lassa Fever/immunology , Lassa Fever/virology , Lassa virus/immunology , Lassa virus/isolation & purification , Polymerase Chain Reaction , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/mortality , Pregnancy Trimester, Third , Public Health , RNA, Viral/analysis , Ribavirin/therapeutic use , Sierra Leone/epidemiology , Young AdultABSTRACT
BACKGROUND: Lassa hemorrhagic fever (LHF) is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV) GP1 (sGP1) in vitro resulting from the expression of the glycoprotein complex (GPC) gene [1, 2]. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses, another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host's inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV), a filovirus that also causes hemorrhagic fever with nearly 90 percent fatality rates [3 - 5]. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention. To this end, we investigated the presence of sGP1 in the serum of suspected LASV patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW), in Kenema, Sierra Leone that tested positive for viral antigen or displayed classical signs of Lassa fever. RESULTS: It is reasonable to expect that a narrow window exists for detection of sGP1 as the sole protein shed during early arenaviral biogenesis. This phenomenon was clearly distinguishable from virion-associated GP1 only prior to the emergence of de novo viral particles. Despite this restricted time frame, in 2/46 suspected cases in two studies performed in late 2009 and early 2010, soluble glycoprotein component shedding was identified. Differential detection of viral antigens GP1, GP2, and NP by western blot yielded five different scenarios: whole LASV virions (GP1, GP2, NP; i.e. active viremia), different combinations of these three proteins, sGP1 only, NP only, and absence of all three proteins. Four additional samples showed inconclusive evidence for sGP1 shedding due to lack of detection of GP2 and NP in western blot; however, a sensitive LASV NP antigen capture ELISA generated marginally positive signals. CONCLUSIONS: During a narrow window following active infection with LASV, soluble GP1 can be detected in patient sera. This phenomenon parallels other VHF infection profiles, with the actual role of a soluble viral glycoprotein component in vivo remaining largely speculative. The expenditure of energy and cellular resources toward secretion of a critical protein during viral biogenesis without apparent specific function requires further investigation. Future studies will be aimed at systematically identifying the role of LASV sGP1 in the infection process and outcome in vitro and in vivo.
Subject(s)
Lassa Fever/virology , Lassa virus/immunology , Viral Envelope Proteins/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antigens, Viral/blood , Antigens, Viral/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Lassa Fever/diagnosis , Lassa virus/physiology , Models, Biological , Viral Envelope Proteins/immunologyABSTRACT
As health professionals develop health communication for coronavirus disease 2019 (COVID-19), we implore that these communication approaches do not include fear appeals. Fear appeals, also known as scare tactics, have been widely used to promote recommended preventive behaviors. We contend that unintended negative outcomes can result from fear appeals that intensify the already complex pandemic and efforts to contain it. We encourage public health professionals to reevaluate their desire to use fear appeals in COVID-19 health communication and recommend that evidence-based health communication be utilized to address the needs of a specific community, help people understand what they are being asked to do, explain step-by-step how to complete preventative behaviors, and consider external factors needed to support the uptake of behaviors. To aid health professionals in redirecting away from the use of fear appeals, we offer a phased approach to creating health communication messages during the COVID-19 crisis.
Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Fear , Global Health , Health Communication/methods , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Betacoronavirus , COVID-19 , Communicable Disease Control/methods , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Risk Factors , SARS-CoV-2ABSTRACT
Recent outbreaks of animal-borne emerging infectious diseases have likely been precipitated by a complex interplay of changing ecological, epidemiological and socio-economic factors. Here, we develop modelling methods that capture elements of each of these factors, to predict the risk of Ebola virus disease (EVD) across time and space. Our modelling results match previously-observed outbreak patterns with high accuracy, and suggest further outbreaks could occur across most of West and Central Africa. Trends in the underlying drivers of EVD risk suggest a 1.75 to 3.2-fold increase in the endemic rate of animal-human viral spill-overs in Africa by 2070, given current modes of healthcare intervention. Future global change scenarios with higher human population growth and lower rates of socio-economic development yield a fourfold higher likelihood of epidemics occurring as a result of spill-over events. Our modelling framework can be used to target interventions designed to reduce epidemic risk for many zoonotic diseases.
Subject(s)
Communicable Diseases, Emerging/virology , Ebolavirus/physiology , Environment , Hemorrhagic Fever, Ebola/virology , Socioeconomic Factors , Zoonoses/virology , Africa/epidemiology , Animals , Communicable Diseases, Emerging/epidemiology , Disease Outbreaks/prevention & control , Epidemics/prevention & control , Hemorrhagic Fever, Ebola/epidemiology , Humans , Risk Factors , Zoonoses/epidemiologyABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
Lassa fever (LF) is increasingly recognized by global health institutions as an important rodent-borne disease with severe impacts on some of West Africa's poorest communities. However, our knowledge of LF ecology, epidemiology and distribution is limited, which presents barriers to both short-term disease forecasting and prediction of long-term impacts of environmental change on Lassa virus (LASV) zoonotic transmission dynamics. Here, we synthesize current knowledge to show that extrapolations from past research have produced an incomplete picture of the incidence and distribution of LF, with negative consequences for policy planning, medical treatment and management interventions. Although the recent increase in LF case reports is likely due to improved surveillance, recent studies suggest that future socio-ecological changes in West Africa may drive increases in LF burden. Future research should focus on the geographical distribution and disease burden of LF, in order to improve its integration into public policy and disease control strategies.
Subject(s)
Lassa Fever/epidemiology , Zoonoses/epidemiology , Africa, Western/epidemiology , Animals , Humans , Incidence , Prevalence , Topography, MedicalABSTRACT
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'.
Subject(s)
Agriculture , Ecosystem , One Health , Zoonoses/epidemiology , Zoonoses/transmission , Africa/epidemiology , Animal Husbandry , Animals , Henipavirus Infections/epidemiology , Henipavirus Infections/transmission , Henipavirus Infections/virology , Humans , Lassa Fever/epidemiology , Lassa Fever/transmission , Lassa Fever/virology , Prevalence , Rift Valley Fever/epidemiology , Rift Valley Fever/transmission , Rift Valley Fever/virology , Trypanosomiasis, African/epidemiology , Trypanosomiasis, African/parasitology , Trypanosomiasis, African/transmission , Zoonoses/parasitology , Zoonoses/virologyABSTRACT
A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.e. transmission of pathogens from animals to humans, and 'stuttering transmission', i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir.
Subject(s)
Disease Outbreaks/prevention & control , Lassa Fever/transmission , Models, Theoretical , Zoonoses/transmission , Animals , Disease Susceptibility , Humans , Rodentia/virologyABSTRACT
BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Formula: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.
Subject(s)
Lassa Fever/transmission , Models, Biological , Zoonoses , Animals , Cross Infection/transmission , Humans , Lassa Fever/epidemiology , Sierra Leone/epidemiologyABSTRACT
Lassa fever is a disease that has been reported from sites across West Africa; it is caused by an arenavirus that is hosted by the rodent M. natalensis. Although it is confined to West Africa, and has been documented in detail in some well-studied areas, the details of the distribution of risk of Lassa virus infection remain poorly known at the level of the broader region. In this paper, we explored the effects of certainty of diagnosis, oversampling in well-studied region, and error balance on results of mapping exercises. Each of the three factors assessed in this study had clear and consistent influences on model results, overestimating risk in southern, humid zones in West Africa, and underestimating risk in drier and more northern areas. The final, adjusted risk map indicates broad risk areas across much of West Africa. Although risk maps are increasingly easy to develop from disease occurrence data and raster data sets summarizing aspects of environments and landscapes, this process is highly sensitive to issues of data quality, sampling design, and design of analysis, with macrogeographic implications of each of these issues and the potential for misrepresenting real patterns of risk.
Subject(s)
Lassa Fever/epidemiology , Lassa Fever/transmission , Topography, Medical/methods , Africa, Western/epidemiology , Geographic Mapping , Geography , Humans , Models, Biological , Quality Control , Risk Assessment/methods , Selection BiasABSTRACT
The Kenema Government Hospital Lassa Fever Ward in Sierra Leone, directed since 2005 by Dr. Sheikh Humarr Khan, is the only medical unit in the world devoted exclusively to patient care and research of a viral hemorrhagic fever. When Ebola virus disease unexpectedly appeared in West Africa in late 2013 and eventually spread to Kenema, Khan and his fellow healthcare workers remained at their posts, providing care to patients with this devastating illness. Khan and the chief nurse, Mbalu Fonnie, became infected and died at the end of July, a fate that they have sadly shared with more than ten other healthcare workers in Kenema and hundreds across the region. This article pays tribute to Sheik Humarr Khan, Mbalu Fonnie and all the healthcare workers who have acquired Ebola virus disease while fighting the epidemic in West Africa. Besides the emotional losses, the death of so many skilled and experienced healthcare workers will severely impair health care and research in affected regions, which can only be restored through dedicated, long-term programs.
Subject(s)
Ebolavirus/physiology , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/history , Africa, Western/epidemiology , Epidemics/history , Health Personnel/history , Hemorrhagic Fever, Ebola/virology , History, 20th Century , History, 21st Century , HumansABSTRACT
Seoul virus, an Old World hantavirus, is maintained in brown rats and causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans. We captured rodents in New Orleans, Louisiana and tested them for the presence of Old World hantaviruses by reverse transcription polymerase chain reaction (RT-PCR) with sequencing, cell culture, and electron microscopy; 6 (3.4%) of 178 rodents captured--all brown rats--were positive for a Seoul virus variant previously coined Tchoupitoulas virus, which was noted in rodents in New Orleans in the 1980s. The finding of Tchoupitoulas virus in New Orleans over 25 years since its first discovery suggests stable endemicity in the city. Although the degree to which this virus causes human infection and disease remains unknown, repeated demonstration of Seoul virus in rodent populations, recent cases of laboratory-confirmed HFRS in some US cities, and a possible link with hypertensive renal disease warrant additional investigation in both rodents and humans.