Clinical Presentation and Outcome of Ribavirin Treated RT-PCR Confirmed Lassa Fever Patients in ISTH Irrua: A Pilot Study

Background: Lassa fever is a viral hemorrhagic fever that is endo-epidemic in Edo state, with case fatality of 90-100% if not treated. It has been claimed that early treatment with Ribavirin reduces mortality to less than 20%. This study was carried out to assert/confirm or refute/reject this claim.Aim: To review the clinical features, laboratory findings of Lassa fever and the outcome of confirmed cases treated with Ribavirin.Methodology: The study was a case series study of the first 41 cases that were treated with Ribavirin in the Lassa fever isolation ward from 28th November 2010 to 26th May 2011.Results: Up to 63.4% of cases presented late (onset of illness greater than 6 days at presentation). Fever remains the predominant presenting feature of the disease (97.5%). Of the cases that were admitted, 41 were treated, 31 recovered and 9 died, giving a case-fatality rate of 22%. One discharged against medical advice. Conclusion: Lassa fever victims still present late at the hospital and fever remains the predominant presenting feature. Early Ribavirin treatment improves treatment outcome of Lassa fever in confirmed cases.Recommendations: The Federal, States and Local government area council members must make efforts to create public awareness on early presentation, diagnosis and prompt treatment with Ribavirin

Assessment of knowledge and practice of oxygen therapy among doctors and nurses: A survey from Ondo State, Southwest Nigeria

Objectives: Oxygen is among the commonly used drugs in acute emergencies. Prescription and administration of oxygen in emergencies by healthcare providers are reported to be inappropriate in most settings. There is a huge gap in the knowledge of health-care providers on various aspects of oxygen therapy. The purpose of this study was to assess the knowledge and practice of oxygen therapy among doctors and nurses working in Ondo State, South-West Nigeria and see how it compares with standard practice with a view to improving the quality care in this regard.Materials and Methods: A descriptive cross-sectional study was employed. The data were collected electronically using the Monkey survey application from consenting doctors and nurses through a self-administered validated and structured questionnaire. The questionnaire included the professional characteristics, educational background, awareness and use of oxygen therapy guidelines, knowledge of oxygen, indication for acute oxygen, and oxygen delivery practices. Data were analyzed using descriptive statistics and association between variables explored with Chi-square test at P < 0.05.Results: One hundred and seventy-six health workers participated in the study with mean age of 37.30 ± 8.88 years. One hundred and twelve (63.60%) of the respondents were doctors while 64 (36.40%) of the respondents were nurses. Sixty-eight (60.70%) of the doctors and 19 (29.70%) of nurses had a high level of knowledge of oxygen therapy (p<0.001). About half of both doctors and nurses had a poor practice level of oxygen therapy. The duration of oxygen administration (how long ago the respondent was involved in oxygen use and previous to formal training on oxygen therapy) were significantly associated with level of knowledge of oxygen therapy (p<0.001, 0.017).Conclusion: Results from this study suggest that the level of knowledge was high in about half of the respondents and about the same percentage had poor oxygen therapy practice in hospitals in Ondo State, South West Nigeria. Therefore, regular training of healthcare workers should be encouraged to update their knowledge and practice of oxygen therapy

Assessment of the willingness of doctors to work at coronavirus disease-19 treatment center

Objectives: The Coronavirus disease 2019 (COVID-19) pandemic is currently ravaging the entire world. Doctors as well as other healthcare workers as front-liners in tackling this disease are at a higher risk of exposure to the virus and its potential consequences. The objectives of this study were to assess the knowledge of doctors on the mode of transmission of the virus, to assess their willingness and readiness to work at the COVID-19 treatment center, to identify factors that affect their willingness to work at the treatment center, and to assess their knowledge on infection prevention and control (IPC) practices.Materials and Methods: All medical doctors who attended the COVID-19 sensitization and preparedness meeting with the management of Federal Medical Centre, Owo, Ondo State Nigeria, were recruited into the study after an informed consent was obtained. Study period spanned from the beginning of April 2020 to middle of June 2020. A structured, pre-tested questionnaire was administered to collect relevant information.Results: A total of 112 doctors that were in attendance had the questionnaires administered to them; however, 106 (94.64%) questionnaires were returned. Out of these, 64.2% had correct knowledge of the mode of transmission of COVID-19. We observed that only 34.9% of doctors were willing to work in the treatment center while 1.9% were indifferent. The perceived lack of adequate training and insufficient personal protective equipment (PPE) for staff were major reasons why some doctors were not willing to work in these centers. Fifty percent of the participants got the correct meaning of donning and doffing and three quarters of them had good knowledge of IPC practice.Conclusion: We found in our study that a substantial number of doctors were unwilling to work in COVID-19 treatment areas due to a number of factors including perceived inadequate PPE and inadequate knowledge. The factors that would influence their willingness to work in COVID-19 treatment center were more training, provision of inducement or extra allowances and life insurance schemes. We recommend that in addition to putting emphasis on training, re-training, and providing appropriate equipment, special inducement allowance, and life insurance for healthcare workers might be helpful to encourage them to work in COVID-19 treatment centers

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

A standardised Phase III clinical trial framework to assess therapeutic interventions for Lassa fever

BACKGROUND: Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. METHODOLOGY: We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. RESULTS: A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. CONCLUSIONS: This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level

Immunological insights into COVID-19 in Southern Nigeria

Introduction: One of the unexpected outcomes of the COVID-19 pandemic was the relatively low levels of morbidity and mortality in Africa compared to the rest of the world. Nigeria, Africa's most populous nation, accounted for less than 0.01% of the global COVID-19 fatalities. The factors responsible for Nigeria's relatively low loss of life due to COVID-19 are unknown. Also, the correlates of protective immunity to SARS-CoV-2 and the impact of pre-existing immunity on the outcome of the COVID-19 pandemic in Africa are yet to be elucidated. Here, we evaluated the natural and vaccine-induced immune responses from vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria throughout the three waves of the COVID-19 pandemic in Nigeria. We also examined the pre-existing immune responses to SARS-CoV-2 from samples collected prior to the COVID-19 pandemic. Methods: We used spike RBD and N- IgG antibody ELISA to measure binding antibody responses, SARS-CoV-2 pseudotype assay protocol expressing the spike protein of different variants (D614G, Delta, Beta, Omicron BA1) to measure neutralizing antibody responses and nucleoprotein (N) and spike (S1, S2) direct ex vivo interferon gamma (IFNγ) T cell ELISpot to measure T cell responses. Result: Our study demonstrated a similar magnitude of both binding (N-IgG (74% and 62%), S-RBD IgG (70% and 53%) and neutralizing (D614G (49% and 29%), Delta (56% and 47%), Beta (48% and 24%), Omicron BA1 (41% and 21%)) antibody responses from symptomatic and asymptomatic survivors in Nigeria. A similar magnitude was also seen among vaccinated participants. Interestingly, we revealed the presence of preexisting binding antibodies (N-IgG (60%) and S-RBD IgG (44%)) but no neutralizing antibodies from samples collected prior to the pandemic. Discussion: These findings revealed that both vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria make similar magnitude of both binding and cross-reactive neutralizing antibody responses. It supported the presence of preexisting binding antibody responses among some Nigerians prior to the COVID-19 pandemic. Lastly, hybrid immunity and heterologous vaccine boosting induced the strongest binding and broadly neutralizing antibody responses compared to vaccine or infection-acquired immunity alone

Emergence and spread of two SARS-CoV-2 variants of interest in Nigeria.

Identifying the dissemination patterns and impacts of a virus of economic or health importance during a pandemic is crucial, as it informs the public on policies for containment in order to reduce the spread of the virus. In this study, we integrated genomic and travel data to investigate the emergence and spread of the SARS-CoV-2 B.1.1.318 and B.1.525 (Eta) variants of interest in Nigeria and the wider Africa region. By integrating travel data and phylogeographic reconstructions, we find that these two variants that arose during the second wave in Nigeria emerged from within Africa, with the B.1.525 from Nigeria, and then spread to other parts of the world. Data from this study show how regional connectivity of Nigeria drove the spread of these variants of interest to surrounding countries and those connected by air-traffic. Our findings demonstrate the power of genomic analysis when combined with mobility and epidemiological data to identify the drivers of transmission, as bidirectional transmission within and between African nations are grossly underestimated as seen in our import risk index estimates

A critical appraisal of COVID-19 as a nosocomial infection: an African perspective

The pandemic of Coronavirus disease 19 is not abating since the outbreak began in December 2019. Africa is currently experiencing a surge after an initial low incidence and nosocomial infections could be contributing to this. A dominant factor responsible for this is a weak healthcare system because of many years of neglect due to abysmal budgetary allocation to the sector. The testing capacity for COVID-19 diagnosis in Africa is grossly inadequate coupled with a severe shortage of personal protective equipment and inadequate infectious diseases expert. These factors exposed the frontline health workers and patients to the hazard of nosocomial infection with the attendants´ morbidity and mortality. Deliberate efforts need to be made toward reducing nosocomial COVID-19 infection

Monitoring of Lassa virus infection in suspected and confirmed cases in Ondo State, Nigeria

Introduction: Lassa virus (LASV), the causative agent of Lassa fever (LF), an endemic acute viral haemorrhagic illness in Nigeria, is transmitted by direct contact with the rodent, contaminated food or household items. Person-to-person transmission also occurs and sexual transmission has been reported. Thus, this study investigated the presence of LASV in body fluids of suspected and confirmed cases. Methods: this was a cross-sectional study between March 2018 and April 2019 involving 112 consenting suspected and post ribavirin confirmed cases attending the Lassa fever treatment center in Ondo State. Whole blood was collected from 57 suspected and 29 confirmed cases. Other samples from confirmed cases were 5 each of High Vaginal Swab (HVS) and seminal fluid; 12 breast milk and 4 urine. All samples were analyzed using reverse transcription-PCR (RT-PCR) targeting the S-gene of LASV. Results: analysis of whole blood by RT-PCR showed that 1/57 (1.8%) suspected and 1/29 (3.4%) confirmed post ribavirin treated cases were positive. While LASV was detected in 2/5 (40%) post ribavirin treated seminal fluids and 1/11 (8.3%) breast milk. However, LASV was not detected in any of the HVS and urine samples. Conclusion: the detection of LASV in seminal fluid and breast milk of discharged post ribavirin treated cases suggests its persistence in these fluids of recovering Nigerians. The role of postnatal and sexual transmissions in the perennial outbreak of LF needs to be further evaluated

Arenavirus Diversity and Phylogeography of Mastomys natalensis Rodents, Nigeria

Mastomys natalensis rodents are natural hosts for Lassa virus (LASV). Detection of LASV in 2 mitochondrial phylogroups of the rodent near the Niger and Benue Rivers in Nigeria underlines the potential for LASV emergence in fresh phylogroups of this rodent. A Mobala-like sequence was also detected in eastern Nigeria