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

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

Aseptic Meningitis Caused by Lassa Virus: Case Series Report

The Lassa virus is known to cause disease in different organ systems of the human body, with varying clinical manifestations. The features of severe clinical disease may include bleeding and/or central nervous system manifestations. Whereas Lassa fever encephalopathy and encephalitis are well described in the literature, there is paucity of data on Lassa virus meningitis. We present the clinical description, laboratory diagnosis, and management of 4 consecutive cases of aseptic meningitis associated with Lassa virus infection without bleeding seen in a region of Nigeria known to be endemic for both the reservoir rodent and Lassa fever. The 4 patients recovered fully following intravenous ribavirin treatment and suffered no neurologic complications

Surgical Management of Massive Pericardial Effusion and Predictors for Development of Constrictive Pericarditis in a Resource Limited Setting

Background. The diagnosis and treatment of massive pericardial effusion and cardiac tamponade have evolved over the years with a tendency towards a more comprehensive diagnostic workup and less traumatic intervention. Method. We reviewed and analysed the data of 32 consecutive patients who underwent surgery on account of massive pericardial effusion and cardiac tamponade in a semiurban university hospital in Nigeria from February 2010 to February 2016. Results. The majority of patients (34.4%) were between 31 and 40 years. Fourteen patients (43.8%) presented with clinical and echocardiographic feature of cardiac tamponade. The majority of patients (59.4%) presented with haemorrhagic pericardial effusion and the average volume of fluid drained intraoperatively was 846 mL  ± 67 mL. Pericardium was thickened in 50% of cases. Subxiphoid pericardiostomy was performed under local anaesthesia in 28 cases. No postoperative recurrence was observed; however 5 patients developed features of constrictive pericarditis. The relationship between pericardial thickness and development of pericardial constriction was statistically significant (p=0.004). Conclusion. Subxiphoid pericardiostomy is a very effective way of treating massive pericardial effusion. Removing tube after adequate drainage (50 mL/day) and treatment of primary pathology are key to preventing recurrence. There is also a need to follow up patients to detect pericardial constriction especially those with thickened pericardium

The Origins and Future of Sentinel: An Early-Warning System for Pandemic Preemption and Response

While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE—detected in the Yoruba population of Nigeria—conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the “emerging” nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz’s critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts