The unusual finding of peripheral lymphadenopathy among confirmed Lassa fever patients in Nigeria.

Lassa fever is a viral haemorrhagic fever belonging to the arenaviridae family that is well known to be endemic to West Africa. The clinical presentation of the disease ranges from asymptomatic to fulminant illness. Lymphadenopathy a clinical manifestation of inflammation, infection, or malignancy has not been widely reported in Lassa fever disease. We report two cases of Lassa fever disease presenting with lymphadenopathy.

Enlargement of lymph nodes, is a common symptom of many infections, however it is not commonly mentioned in patients with Lassa fever, a viral hemorrhagic fever that is endemic in West Africa. However, recent research suggests that lymphadenopathy may be underreported in Lassa fever patients. This new finding could have important implications for the diagnosis and treatment of the disease, as well as for our understanding of how it spreads.

Lassa fever outcomes and prognostic factors in Nigeria (LASCOPE): a prospective cohort study.

BACKGROUND: Lassa fever is a viral haemorrhagic fever endemic in parts of west Africa. New treatments are needed to decrease mortality, but pretrial reference data on the disease characteristics are scarce. We aimed to document baseline characteristics and outcomes for patients hospitalised with Lassa fever in Nigeria. METHODS: We did a prospective cohort study (LASCOPE) at the Federal Medical Centre in Owo, Nigeria. All patients admitted with confirmed Lassa fever were invited to participate and asked to give informed consent. Patients of all ages, including newborn infants, were eligible for inclusion, as were pregnant women. All participants received standard supportive care and intravenous ribavirin according to Nigeria Centre for Disease Control guidelines and underwent systematic biological monitoring for 30 days. Patients' characteristics, care received, mortality, and associated factors were recorded using standard WHO forms. We used univariable and multivariable logistic regression models to investigate an association between baseline characteristics and mortality at day 30. FINDINGS: Between April 5, 2018, and March 15, 2020, 534 patients with confirmed Lassa fever were admitted to hospital, of whom 510 (96%) gave consent and were included in the analysis. The cohort included 258 (51%) male patients, 252 (49%) female patients, 426 (84%) adults, and 84 (16%) children (younger than 18 years). The median time between first symptoms and hospital admission was 8 days (IQR 7-13). At baseline, 176 (38%) of 466 patients had a Lassa fever RT-PCR cycle threshold (Ct) lower than 30. From admission to end of follow-up, 120 (25%) of 484 reached a National Early Warning Score (second version; NEWS2) of 7 or higher, 67 (14%) of 495 reached a Kidney Disease-Improving Global Outcome (KDIGO) stage of 2 or higher, and 41 (8%) of 510 underwent dialysis. All patients received ribavirin for a median of 10 days (IQR 9-13). 62 (12%) patients died (57 [13%] adults and five [6%] children). The median time to death was 3 days (1-6). The baseline factors independently associated with mortality were the following: age 45 years or older (adjusted odds ratio 16·30, 95% CI 5·31-50·30), NEWS2 of 7 or higher (4·79, 1·75-13·10), KDIGO grade 2 or higher (7·52, 2·66-21·20), plasma alanine aminotransferase 3 or more times the upper limit of normal (4·96, 1·69-14·60), and Lassa fever RT-PCR Ct value lower than 30 (4·65, 1·50-14·50). INTERPRETATION: Our findings comprehensively document clinical and biological characteristics of patients with Lassa fever and their relationship with mortality, providing prospective estimates that could be useful for designing future therapeutic trials. Such trials comparing new Lassa fever treatments to a standard of care should take no more than 15% as the reference mortality rate and consider adopting a combination of mortality and need for dialysis as the primary endpoint. FUNDING: Institut National de la Santé et de la Recherche Médicale, University of Oxford, EU, UK Department for International Development, Wellcome Trust, French Ministry of Foreign Affairs, Agence Nationale de Recherches sur le SIDA et les hépatites virales, French National Research Institute for Sustainable Development.

Association of hypoalbuminemia and reversal of albumin-to-globulin ratio with morbidity outcome among hospitalized Lassa fever infected patients at a dedicated treatment center in Ondo state, south-western Nigeria.

BACKGROUND: As of this present moment, there is paucity of data on report concerning the association between hypoalbuminaemia or reversal of albumin-to-globulin ratio and morbidity outcome in Lassa fever (LF) infection as a crucial determinant prognostic-predictor factor for treatment-survival outcome. AIM: This study was designed to determine the association between hypoalbuminaemia, reversal of albumin-to-globulin ratio and morbidity outcome among confirmed LF infected patients. METHODOLOGY: This was a descriptive retrospective study involving the assessment of records of confirmed LF infected patients that were managed at the center from November 2018 to October 2019. RESULTS: Out of 83 recruited participants with complete records, 66 (79.5%) had hypoalbuminaemia, 74 (89.2%) had reversal of albumin-to-globulin ratio. A higher mean value of total white blood cell (WBC) count was observed among patients with hypoalbuminaemia (p < 0.0001) and reversal of albumin-to-globulin ratio (p < 0.0001) when compared to patients with normal values, respectively. Also, this study showed statistically significant associations between serum albumin level versus total WBC count (p < 0.0001), acute kidney injury (AKI; p = 0.009), bleeding diathesis (p < 0.0001), and occurrence of pregnancy miscarriage (p < 0.0001). CONCLUSION: There is a baseline hypoalbuminaemia and reversal of albumin-to-globulin ratio among confirmed LF infected patients. Based on these findings, the serum level of albumin and albumin-to-globulin ratio at presentation may serve as simple early biomarkers to identify patients at high risk for a complicated clinical course of disease. This study also reveals that those hospitalized LF infected patients with hypoalbuminemia and/or reversal of albumin-to-globulin ratio tend to have leucocytosis and experience prolonged duration of illness.

Lassa fever clinical course and setting a standard of care for future randomized trials: A protocol for a cohort study of Lassa-infected patients in Nigeria (LASCOPE).

BACKGROUND: Lassa Fever (LF), is a severe viral disease prevalent in Western Africa. It is classified as a priority disease by the World Health Organization (WHO). Ribavirin is the recommended therapy despite weak evidence of its efficacy. Promising therapeutic agents are becoming available for evaluation in human. Before launching therapeutic trials, we need data on the evolution of the disease under the best possible conditions of care. METHODS: We have initiated a prospective study in Nigeria to better understand the clinical course and prognostic factors of LF while implementing high quality standardized care. Inclusion criteria are: suspected or confirmed LF and informed consent. Participants are followed 60 days from admission and receive free of charge standardized supportive care and biological monitoring, as well as intravenous ribavirin for those with confirmed LF. Data are collected using standardized case report forms (CRF). Primary and secondary outcomes are fatality and severe morbidity, with special focus on acute kidney dysfunction and pregnancy complications. Factors associated with outcomes will be investigated. RESULTS: The cohort is planned for 3 years. Inclusions started in April 2018 at the Federal Medical Center Owo in Ondo State. A second site will open in Nigeria in 2020 and discussions are underway to open a site in Benin. 150 to 200 new participants are expected per year. CONCLUSIONS: This cohort will: provide evidence to standardize LF case management; provide key inputs to design future clinical trials of novel therapeutics; and establish clinical research teams capable of conducting such trials in LF-endemic areas. STUDY REGISTRATION: The LASCOPE study was registered on ClinicalTrial.gov (NCT03655561).