The niche of One Health approaches in Lassa fever surveillance and control.

Lassa fever (LF), a zoonotic illness, represents a public health burden in West African countries where the Lassa virus (LASV) circulates among rodents. Human exposure hinges significantly on LASV ecology, which is in turn shaped by various parameters such as weather seasonality and even virus and rodent-host genetics. Furthermore, human behaviour, despite playing a key role in the zoonotic nature of the disease, critically affects either the spread or control of human-to-human transmission. Previous estimations on LF burden date from the 80s and it is unclear how the population expansion and the improvement on diagnostics and surveillance methods have affected such predictions. Although recent data have contributed to the awareness of epidemics, the real impact of LF in West African communities will only be possible with the intensification of interdisciplinary efforts in research and public health approaches. This review discusses the causes and consequences of LF from a One Health perspective, and how the application of this concept can improve the surveillance and control of this disease in West Africa

Molecular Diagnostics for Lassa Fever at Irrua Specialist Teaching Hospital, Nigeria: Lessons Learnt from Two Years of Laboratory Operation

Background: Lassa fever is a viral hemorrhagic fever endemic in West Africa. However, none of the hospitals in the endemic areas of Nigeria has the capacity to perform Lassa virus diagnostics. Case identification and management solely relies on non-specific clinical criteria. The Irrua Specialist Teaching Hospital (ISTH) in the central senatorial district of Edo State struggled with this challenge for many years. Methodology/Principal Findings A laboratory for molecular diagnosis of Lassa fever, complying with basic standards of diagnostic PCR facilities, was established at ISTH in 2008. During 2009 through 2010, samples of 1,650 suspected cases were processed, of which 198 (12%) tested positive by Lassa virus RT-PCR. No remarkable demographic differences were observed between PCR-positive and negative patients. The case fatality rate for Lassa fever was 31%. Nearly two thirds of confirmed cases attended the emergency departments of ISTH. The time window for therapeutic intervention was extremely short, as 50% of the fatal cases died within 2 days of hospitalization—often before ribavirin treatment could be commenced. Fatal Lassa fever cases were older (p = 0.005), had lower body temperature (p<0.0001), and had higher creatinine (p<0.0001) and blood urea levels (p<0.0001) than survivors. Lassa fever incidence in the hospital followed a seasonal pattern with a peak between November and March. Lassa virus sequences obtained from the patients originating from Edo State formed—within lineage II—a separate clade that could be further subdivided into three clusters. Conclusions/Significance: Lassa fever case management was improved at a tertiary health institution in Nigeria through establishment of a laboratory for routine diagnostics of Lassa virus. Data collected in two years of operation demonstrate that Lassa fever is a serious public health problem in Edo State and reveal new insights into the disease in hospitalized patients.Organismic and Evolutionary Biolog

Lassa Fever Infection among Healthcare Workers during the 2018 Outbreak in Nigeria

Introduction: Healthcare workers (HCWs) are potentially exposed to infection during viral hemorrhagic fever outbreaks. In the wake of 2018, Nigeria experienced an unprecedented surge in cases of Lassa fever (LF), which affected HCWs. To guide infection prevention and control (IPC) strategies in similar settings, we characterize HCWs' infection and describe the gaps in IPC standards and practices during the outbreak. Methods: Data was collected using a structured questionnaire, interview, and review of case notes of 21 HCW with laboratory-confirmed Lassa fever who were treated at the Irrua Specialist Teaching Hospital (ISTH) Irrua and the Alex-Ekwemen Federal Teaching Hospital, Abakaliki (AEFETHA), between 1st January and 27th May 2018. Information collected was the patients' socio-demographic characteristics, date of potential exposure and onset of illness, nature, and type of exposure, clinical features, outcome, use of personal protective equipment (PPE), and personnel IPC training and were analyzed using descriptive statistics with Microsoft Excel. Results: The study included 21 HCWs, and 12 (57.14%) were doctors. The case fatality rate was 23%. Nearly two-thirds (62%) of the HCWs could describe a likely procedure leading to their exposure and infection. Among 13 HCWs, 85% had multiple blood and body fluids exposure, while 15% had needle stick injury or scalpel cut. About one-fifth of the participants had received some IPC training. Conclusion: Limited IPC adherence and inappropriate risk assessment were identified as factors leading to Lassa fever exposure and infection among HCWs. There is an urgent need to provide IPC training for all HCWs and to ensure an adequate supply of IPC materials to all healthcare facilities as part of emergency preparedness, especially in LF endemic areas

Acute Lassa Virus Encephalitis with Lassa Virus in the Cerebrospinal Fluid but Absent in the Blood: A Case Report with a Positive Outcome

It is rare both to have the central nervous system (CNS) as the main focus in the acute phase of Lassa fever infection without associated bleeding, and to find Lassa virus (LAV) in the cerebrospinal fluid (CSF) but not in the serum. We report the case of a 38-year-old Nigerian woman with mainly CNS manifestation of Lassa fever. She was admitted twice within 11 days because of persistent fever. A clinical diagnosis of acute LAV encephalitis was made because of a high index of suspicion and CNS involvement confirmed by positive reverse transcriptase polymerase chain reaction (RT-PCR) for LAV in the CSF, while her blood was repeatedly negative for LAV by RT-PCR test. She recovered fully following supportive care coupled with treatment with an 18-day course of ribavirin, and suffered no long-term neurological complication or relapse. Post-treatment CSF examination by RT-PCR did not detect LAV

Recent advances in the development and evaluation of molecular diagnostics for Ebola virus disease

The 2014-16 outbreak of ebola virus disease (EVD) in West Africa resulted in 11,308 deaths. During the outbreak only 60% of patients were laboratory confirmed and global health authorities have identified the need for accurate and readily deployable molecular diagnostics as an important component of the ideal response to future outbreaks, to quickly identify and isolate patients. Areas covered: Currently PCR-based techniques and rapid diagnostic tests (RDTs) that detect antigens specific to EVD infections dominate the diagnostic landscape, but recent advances in biosensor technologies have led to novel approaches for the development of EVD diagnostics. This review summarises the literature and available performance data of currently available molecular diagnostics for ebolavirus, identifies knowledge gaps and maps out future priorities for research in this field. Expert opinion: While there are now a plethora of diagnostic tests for EVD at various stages of development, there is an acute need for studies to compare their clinical performance, but the sporadic nature of EVD outbreaks makes this extremely challenging, demanding pragmatic new modalities of research funding and ethical/institutional approval, to enable responsive research in outbreak settings. Retrospective head-to-head diagnostic comparisons could also be implemented using biobanked specimens, providing this can be done safely

Is Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic. Lessons from past outbreaks, ongoing pan-African public health efforts, and implications for the future

Soon after the novel coronavirus, SARS-CoV-2 (2019-nCoV), was first identified in a cluster of patients with pneumonia (Li et al., 2020), in the Chinese city of Wuhan on 31 December 2019, rapid human to human transmission was anticipated (Hui et al., 2020). The fast pace of transmission is wreaking havoc and stirring media hype and public health concern (Ippolito et al., 2020) globally. When the World Health Organization (WHO) declared the disease, (now officially named COVID-19) a Public Health Emergency of International Concern (PHEIC) on 31st January 2020 (WHO, 2020a), the Director General Dr Tedros Ghebreyesus justified the decision by stating that WHOs greatest concern was the potential for the virus to spread to countries with weaker health systems. Repeated outbreaks of other preventable emerging and re-emerging infectious diseases with epidemic potential have taken their toll on the health systems of many African countries. The devastating 2014–2016 Ebola Virus Epidemic (WHO, 2020b) in West Africa, demonstrated how ill-prepared the affected countries were to rapidly identify the infection and halt transmission (WHO, 2020d, Largent, 2016, Hoffman and Silverberg, 2018, Omoleke et al., 2016). Similarly, the smoldering remnants of the 2018–19 Ebola Virus outbreak in the Democratic Republic of Congo, have demonstrated even for health services with considerable experience of dealing with a certain emerging pathogen, geography and sociopolitical instability, can hamper the response (Aruna et al., 2019)

Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever

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

Virus genomes reveal factors that spread and sustained the Ebola epidemic.

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics

Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa

West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.status: publishe