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.

Pharmacokinetics of Ribavirin in the Treatment of Lassa Fever: An Observational Clinical Study at the Irrua Specialist Teaching Hospital, Edo State, Nigeria.

BACKGROUND: Lassa fever is endemic in large parts of West Africa. The recommended antiviral treatment is ribavirin. Two treatment regimens are currently endorsed in Nigeria: the "McCormick regimen" based on a study published in 1986 and the "Irrua regimen" constituting a simplified schedule developed at the Irrua Specialist Teaching Hospital, Nigeria. Evidence for the safety and efficacy of ribavirin in Lassa fever patients is poor and pharmacokinetic data for both regimens are lacking. METHODS: Polymerase chain reaction-confirmed Lassa fever patients with mild to moderate disease severity were invited to participate in this prospective, observational pharmacokinetic study. Pharmacokinetics of ribavirin, clinical, virologic, and clinical laboratory parameters were assessed. RESULTS: Using a population pharmacokinetic approach, plasma concentrations of ribavirin were best described by a 3-compartment model. Drug exposure was remarkably consistent between participants. Overall, drug clearance was 28.5% lower in female compared with male participants. Median (5th-95th percentile) time above half maximal inhibitory concentration (IC50) was 37.3% (16.9%-73.1%), 16.7% (8.2%-58.5%), and 9.6% (4.9%-38.4%) on days 1, 7, and 8, respectively. Clinical laboratory parameters indicated reduction of cell damage and development of hemolytic anemia in the course of the treatment period. CONCLUSIONS: This observational study characterizes the pharmacokinetics of ribavirin in the treatment of Lassa fever indicating consistent exposure across patients. Whereas only a short time interval of concentrations above the IC50 implies rather low antiviral efficacy in vivo, the prominent reduction of cell damage markers might point to indirect-potentially anti-inflammatory-effects of ribavirin. The role of ribavirin in the treatment of Lassa fever requires further scrutiny.

Two Cases of Lassa Fever Successfully Treated with Ribavirin and Adjunct Dexamethasone for Concomitant Infections.

Lassa fever is a viral hemorrhagic fever treated with supportive care and the broad-spectrum antiviral drug ribavirin. The pathophysiology, especially the role of hyperinflammation, of this disease is unknown. We report successful remission of complicated Lassa fever in 2 patients in Nigeria who received the antiinflammatory agent dexamethasone and standard ribavirin.

Psychiatric manifestations and associated risk factors among hospitalised patients with COVID-19 in Edo State, Nigeria: a cross-sectional study.

OBJECTIVE: To estimate the prevalence of depression and anxiety and identify associated risk factors in hospitalised persons with confirmed COVID-19 in Edo, Nigeria. DESIGN: A multicentre cross-sectional survey. SETTING: Patients with COVID-19 hospitalised at the three government-designated treatment and isolation centres in Edo State, Nigeria. PARTICIPANTS: The study was conducted from 15 April to 11 November 2020 among 489 patients with confirmed COVID-19 and in treatment and isolation centres in Edo State, Nigeria. The mean age of participants was 43.39 (SD=16.94) years. Male participants were 252 (51.5%) and female were 237 (48.5%). MAIN OUTCOME MEASURES: The nine-item Patient Health Questionnaire for depression, (total score: 0-27, depression ≥10), Generalized Anxiety Disorder-7 for anxiety (total score: 0-21, anxiety ≥10), and social demographic and clinical characteristics for associated risk factors. RESULTS: Of the 489 participants, 49.1% and 38.0% had depressive and anxiety symptoms, respectively. The prevalence rates of depression, anxiety and combination of both were 16.2%, 12.9% and 9.0%, respectively. Moderate-severe symptoms of COVID-19, ≥14 days in isolation, worrying about the outcome of infection and stigma increased the risk of having depression and anxiety. Additionally, being separated/divorced increased the risk of having depression and having comorbidity increased the risk of having anxiety. CONCLUSION: A substantial proportion of our participants experienced depression, anxiety and a combination of both especially in those who had the risk factors we identified. The findings underscore the need to address modifiable risk factors for psychiatric manifestations early in the course of the disease and integrate mental health interventions and psychosocial support into COVID-19 management guidelines.

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.

Prospective observational study on the pharmacokinetic properties of the Irrua ribavirin regimen used in routine clinical practice in patients with Lassa fever in Nigeria.

INTRODUCTION: Lassa fever (LF) is a severe and often fatal systemic disease in humans and affects a large number of countries in West Africa. Treatment options are limited to supportive care and the broad-spectrum antiviral agent ribavirin. However, evidence for ribavirin efficacy in patients with LF is poor and pharmacokinetic (PK) data are not available.Irrua Specialist Teaching Hospital (ISTH) developed an intravenous ribavirin regimen different to the WHO recommendation. Apart from a lower total daily dose the drug is usually administered once per day which reduces the exposure of personnel to patients with LF. The aim of this study is to characterise the PK of the Irrua ribavirin regimen. METHODS AND ANALYSIS: This prospective, observational clinical study will assess PK properties of the Irrua ribavirin regimen on routinely ribavirin-treated patients with LF at ISTH, a referral hospital serving 19 local governmental areas in a LF endemic zone in Nigeria. Participants will be adults with PCR-confirmed LF. The primary objective is to describe classical PK parameters for ribavirin (maximum plasma drug concentration, time to maximum plasma drug concentration, area under the plasma drug concentration vs time curve, half-life time T1/2, volume of distribution). Blood samples will be collected at 0.5, 1, 3, 5, 8, 12 and 24 hours after doses on day 1, day 4 and day 10 of ribavirin treatment. Ribavirin plasma concentrations will be determined using liquid chromatography coupled to tandem mass spectrometry. ETHICS AND DISSEMINATION: The study will be conducted in compliance with the protocol, the Declaration of Helsinki, Good Clinical Practice (GCP) and the Nigerian National Code for Health Research Ethics. The protocol has received approval by the Health Research Ethics Committee of ISTH. Results will be made available to LF survivors, their caregivers, the funders, LF research society and other researchers. REGISTRATION DETAILS: ISRCTN11104750.

Prevalence of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in a tertiary institution, South-South Nigeria.

BACKGROUND: The risk of chronic metformin pharmacotherapy to cause vitamin B12 deficiency and its associated medical complications has been of immense concern among diabetic patients. Some studies have postulated that vitamin B12 deficiency is highly prevalent among chronic metformin-treated adult diabetic patients. AIM: This study aimed to determine the prevalence of vitamin B12 deficiency among metformin-treated and metformin-naïve type 2 diabetes mellitus patients. MATERIALS AND METHODS: This was a case-control, prospective, analytical, observational study of 200 adult participants (100 per group) attending the Endocrinology, Medical Out-patients Clinic of Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria. The participants' serum vitamin B12 levels were determined using an immunoassay technique. Data were presented using tables and charts. Chi-square test was used to compare non-continuous proportional variables. RESULTS: The prevalence of vitamin B12 deficiency was 41% and 20% among metformin-treated and metformin-naïve type 2 diabetes mellitus groups, respectively (p = 0.001). Borderline vitamin B12 status was present among 59% of metformin-treated group and 80% of metformin-naïve group (p = 0.001). Neither metformin-treated nor metformin-naïve groups had normal serum vitamin B12 levels. CONCLUSION: The prevalence of vitamin B12 deficiency was significantly high in diabetics, especially the metformin-treated patients. We advocate for vitamin B12 supplementation among this group of patients in order to prevent the occurrence of vitamin B12 deficiency complications such as macro-ovalocytic anemia, impaired immunity with hypersegmented neutrophils, peripheral neuropathy and subacute degeneration of the spinal cord.

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.

Assessment of prescribed medications and pattern of distribution for potential drug-drug interactions among chronic kidney disease patients attending the Nephrology Clinic of Lagos University Teaching Hospital in Sub-Saharan West Africa.

INTRODUCTION: Life expectancy has increased significantly among chronic kidney disease (CKD) patients due to the extensive use of polypharmacy practice for medication prescriptions. This predisposes them to potential drug-drug interactions (DDIs), which can lead to an increase in morbidity, mortality, length of hospital stay, and health care cost. METHODS: This was a 30-month retrospective study that reviewed the medical case records of consenting adult CKD patients from January 2014 to June 2016. The Medscape drug reference database was used to evaluate patients' medications for potential DDIs. RESULTS: This study involved 123 adult CKD patients (63 [51.22%] males and 60 [48.78%] females) with a mean age of 53.81±16.03 years. The most common comorbid conditions were hypertension (112 [91.10%]) and diabetes mellitus (45 [36.60%]). Regarding the form of nephrological interventions being offered, the majority of the respondents - 66 (53.66%) were on maintenance dialysis, followed by 53 (43.09%) respondents on conservative care, while 4 (3.25%) respondents were on renal transplantation. A total of 1264 prescriptions were made, and the mean number of prescribed medications per patient was 10.28±3.85. The most frequently prescribed medications were furosemide (88 [71.6%]), heparin (67 [54.47%]), lisinopril (65 [52.9%]), oral calcium carbonate (CaCO3) (63 [51.2%]), α-calcidol (62 [50.4%]), and erythropoietin (61 [49.6%]). A total number of 1851 potential DDIs were observed among 118 patients. The prevalence of potential DDIs in this study was 78.0%, while the mean DDI per prescription was 1.50. Among the potential DDIs observed, the severity was mild in 639 (34.5%) patients, moderate in 1160 (62.7%) patients, and major in 51 (2.8%) patients and only 1 (0.1%) patient was of contraindicated drug combination. The most frequent DDIs' pattern observed was between oral CaCO3 and oral ferrous sulfate. There was a statistically significant association between the number of prescribed medications and the estimated glomerular filtration rate (eGFR; pre-ESRD and ESRD staging) with a P-value of 0.00000119. This implies that the number of prescribed medications increases as the eGFR declines in advance CKD stage patients. CONCLUSION: Most of these interactions have moderate severity and delayed onset, hence the need to follow-up these patients after prescription in order to reduce associated morbidity, mortality, length of hospital stay, and health care cost. Physicians and clinical pharmacists should utilise available interaction software to avoid harmful DDIs in these patients.