Combating the zoonotic trio of Ebola virus disease, Lassa fever, and COVID-19 in Nigeria: a retrospection of the challenges and lessons.

Various infectious disease outbreaks linked to zoonotic sources have been recorded over the years, some of which have resulted in epidemics on a national, regional, or global scale. In Africa, a number of such outbreaks occur intermittently, especially in countries like Nigeria with a high-risk of epidemiological transmission. Three viral outbreaks with zoonotic links have hit the Nigerian healthcare system hardest, which are the Ebola virus disease, Lassa fever and Coronavirus disease 2019. Due to the fragile nature of the Nigerian health system, several challenges were encountered in the process of responding to these viral outbreaks, some of which included inadequate healthcare infrastructure, limited diagnostic capacity, unfledged nature of emergency response, unsatisfactory remuneration of health workers, misinformation trends, amongst others. By reminiscing on the challenges and lessons learnt from these viral disease outbreaks, the Nigerian government and policymakers will be able to adopt more effective approaches towards emergency preparedness for future outbreaks of infectious diseases.

The role of community-based approaches in achieving universal health coverage: addressing the Nigerian narrative.

Universal health coverage (UHC) is aimed at ensuring that individuals and communities have affordable access to essential health care services without facing financial hardship. Achieving UHC and the third sustainable development goal of the United Nations requires that health systems transition from a vertical, top-down, curative approach toward one that puts people at the core of health care services, such as community-centered health interventions. Nigeria operates a decentralized health care system with the least focus on primary health care, making access to quality, and affordable health care for several citizens a challenge as the major percentage of the Nigerian population relies on primary health care services. The limited number of health care workers, the poor economic state, the inadequate health financing structures and high illiteracy rates have led to challenges such as low health service availability, hesitancy to utilize health interventions, high out-of-pocket expenditure rates, and health misinformation. These can be effectively tackled at the community level by revamping primary health care services, adequate and sustainable health financing, establishing Ward Development Committees, and the involvement of community stakeholders in health policy implementation. Employing such community-based approaches will ensure continuous progress of the Nigerian health care system toward UHC.

No country for old livers? Examining and optimizing the utilization of elderly liver grafts.

Of the 1.6 million patients >70 years of age who died of stroke since 2002, donor livers were retrieved from only 2402 (0.15% yield rate). Despite reports of successful liver transplantation (LT) with elderly grafts (EG), advanced donor age is considered a risk for poor outcomes. Centers for Medicare and Medicaid Services definitions of an "eligible death" for donation excludes patients >70 years of age, creating disincentives to donation. We investigated utilization and outcomes of recipients of donors >70 through analysis of a United Network for Organ Sharing Standard Transplant Analysis and Research-file of adult LTs from 2002 to 2014. Survival analysis was conducted using Kaplan-Meier curves, and Cox regression was used to identify factors influencing outcomes of EG recipients. Three thousand one hundred four livers from donors >70, ≈40% of which were used in 2 regions: 2 (520/3104) and 9 (666/3104). Unadjusted survival was significantly worse among recipients of EG compared to recipients of younger grafts (P < .0001). Eight independent negative predictors of survival in recipients of EG were identified on multivariable analysis. Survival of low-risk recipients who received EG was significantly better than survival of recipients of younger grafts (P = .04). Outcomes of recipients of EG can therefore be optimized to equal outcomes of younger grafts. Given the large number of stroke deaths in patients >70 years of age, the yield rate of EGs can be maximized and disincentives removed to help resolve the organ shortage crisis.

Optimal timing for hepatitis C therapy in US patients eligible for liver transplantation: a cost-effectiveness analysis.

BACKGROUND: Recurrence of hepatitis C virus (HCV) following liver transplantation (LT) is universal for those with ongoing viraemia and is associated with higher rates of allograft failure and death. However, the optimal timing of HCV treatment for patients awaiting transplant remains unclear. AIM: To evaluate the comparative cost-effectiveness of treating HCV pre-LT vs. post-LT (pre-emptive or after HCV recurrence). METHODS: A Markov state-transition model was created to simulate the progression of a cohort of HCV-genotype 1 or 4 cirrhotic patients from the time of transplant listing until death. We then used this model to study the cost-effectiveness of ledipasvir-sofosbuvir (LDV/SOF) with ribavirin for 12 weeks, administered for three separate treatment strategies: (i) pre-LT; (ii) post-LT preemptively prior to HCV recurrence; or (iii) post-LT after HCV recurrence. RESULTS: In the base-case analysis using a median model for end-stage liver disease (MELD) score <25 at the time of transplant, we found that pre-LT treatment of HCV led to more QALYs for fewer dollars compared to other strategies. Analysis limited to living donor LT recipients revealed that pre-LT treatment was also the most cost-effective strategy. When the analysis was repeated for MELD ≥25, decompensated disease (Child-Pugh class B or C), and hepatocellular carcinoma cases, preemptive post-LT strategy was more cost-effective. CONCLUSIONS: Treatment of HCV prior to liver transplantation appears to be the most cost-effective strategy for patients with a MELD score <25. For patients with a MELD ≥25 or decompensated cirrhosis, preemptive post-liver transplantation treatment before HCV recurrence is the most cost-effective strategy.

Baseline characteristics of the transient pattern electroretinogram in non-human primates: inter-ocular and inter-session variability.

This study assessed the inter-ocular and inter-session variability of the transient pattern electroretinogram (PERG) in a group of non-human primates. The transient PERG was measured both eyes of 29 non-human primates, and again after three months in 23 eyes of 23 of these animals. Signals were elicited using a contrast (90%, 75 cdm(-2)) reversing (5 reversals sec(-1)) checkerboard pattern (0.56 cpd). PERGs were also measured for stimuli of varied spatial frequency (n=8, 0.07-2.22 cpd), contrast (n=4, 20-100%), mean luminance (n=4, 4.7-75 cdm(-2)) and defocus (n=5, +1, +2, +3 diopters). The inter-eye and inter-session limits-of-agreement (LOA; 95%) were determined for each PERG parameter. Variability was also compared with previous studies using the coefficient-of-variability (COV). Pharmacological blockade of the inner retinal contributions to the PERG measured under these conditions was conducted in one animal using intravitreal injection of tetrodotoxin (approximately 6 microM) and N-methyl-D-aspartic acid (approximately 6 microM). The N95 component of the primate transient PERG showed spatial tuning, with a peak between 0.14 and 0.28cpd. This spatial tuning was not as apparent for the P50 component. A linear relationship between P50 and N95 amplitude was found with contrast and mean luminance. Both components were attenuated with the introduction of +2 diopters or more of defocus. The inter-session COV for the P50 and N95 components were 23.8 and 19.2%, respectively, while the LOA were 58 and 46%, respectively. The N95:P50 ratio had smaller inter-session variability, was robust to changes in contrast, mean luminance and defocus, and was effective for characterization of inner-retinal dysfunction after pharmacologic block.

The topographic relationship between multifocal electroretinographic and behavioral perimetric measures of function in glaucoma.

PURPOSE: To study the spatial relationship between local functional abnormalities found using multifocal electroretinography (MERG) and those measured using standard automated perimetry (SAP) in a group of glaucoma patients with well-defined, localized visual field loss. METHODS: MERG's were measured for 15 patients with longstanding, stable, localized SAP visual field loss and for 27 normal controls using VERIS Science (EDI, San Mateo, CA). Most glaucoma patients had substantial asymmetry of visual field defects across the horizontal midline so that within-eye comparisons of MERG changes could be made in addition to comparisons between glaucoma and healthy, aged-matched controls. RESULTS: For the glaucoma patient group as a whole, conventional measurements of MERG responses, such as peak-to-trough amplitude, peak implicit time, and scalar-product density, did not reveal abnormalities that spatially corresponded to local sensitivity losses determined by SAP visual field thresholds. Some of the patients had MERG abnormalities (e.g., reduced amplitudes) in areas of advanced SAP visual field loss that indicated local retinal dysfunction. On average, glaucoma patients were missing a MERG component that resembled the optic nerve head component as described by Sutter and Bearse. CONCLUSIONS: Different MERG components may be affected at different stages of glaucoma, perhaps reflecting a diversity of pathophysiologic mechanisms. This may complicate spatial and temporal relationships between abnormalities found using the MERG and behavioral perimetry, particularly when conventional measurements of MERG responses are used to characterize a diverse patient group/disease.

The fast oscillation of the electrooculogram reveals sensitivity of the human outer retina/retinal pigment epithelium to glucose level.

The effect of acute blood glucose elevations on human outer retinal function was examined. Electrooculograms were recorded as the background light cycled on/off with a 2-min period, eliciting rapid changes in the corneo-retinal standing potential known as the fast-oscillation of the electrooculogram. Recordings were made while subjects fasted and after they consumed 100 g of D-glucose. In all subjects, blood glucose levels strongly affected fast oscillation amplitude, which reflects photoreceptor-driven changes in RPE cell chloride concentration. The sensitivity of RPE metabolism to glucose fluctuations may relate to changes in the blood-retinal barrier that are known to occur in diabetes (e.g. macular edema).

Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy.

PURPOSE: To identify local retinal abnormalities in diabetic patients with and without retinopathy, by using the multifocal electroretinogram (M-ERG). METHODS: Electroretinograms were recorded at 103 discrete retinal locations in each eye of eight persons with nonproliferative diabetic retinopathy (NPDR) and eight diabetic persons without retinopathy, using VERIS (EDI, San Mateo, CA). The amplitude and implicit time of each local (first-order) retinal response were derived and compared with normal values obtained from 16 age-matched, nondiabetic subjects. Maps of local response amplitude and implicit time were compared with fundus photographs taken at the time of testing. RESULTS: In eyes with NPDR, the implicit times of responses from retinal sites manifesting clinical pathologic fundus lesions (e.g., microaneurysms and focal edema), were markedly delayed (e.g., up to 7 msec from normal). Responses from adjacent retinal sites that were more normal in clinical appearance were also delayed, but to a lesser extent (e.g., 2-5 msec). Smaller, yet significant local response delays were also found in eyes without retinopathy. By contrast, local response amplitudes bore no consistent relationship to fundus abnormalities in eyes with retinopathy, and amplitudes were typically normal in eyes without retinopathy. CONCLUSIONS: The M-ERG reveals local retinal dysfunction in diabetic eyes even before retinopathy. The magnitude of delay of local ERG implicit time reflects the degree of local clinical abnormality in eyes with retinopathy. Local response delays found in some eyes without retinopathy suggest that the M-ERG detects subclinical local retinal dysfunction in diabetes. Analysis of M-ERG implicit time, independent of amplitude, improves the sensitivity of detection of local retinal dysfunction in diabetes.