A Rare Tick Tale: A Novel Case of the Australian Paralysis Tick Causing Multiple Cranial Neuropathies.

The Australian paralysis tick (Ixodes holocyclus) is found along the east coast of Australia. Tick bites may result in paralysis ranging from muscular weakness to ascending paralysis requiring respiratory support. Ocular complications and facial nerve involvement are rare. We present a rare occurrence of tick-bite-associated visual loss, proptosis, and multiple cranial neuropathies not previously reported in the literature. The tick was removed, and the patient's symptoms improved following treatment with steroids and oral doxycycline. The vision and sensory changes are not explained by the Ixodes toxin; thus, we hypothesize this is related to orbital apex inflammation.

Genomic epidemiology uncovers the timing and origin of the emergence of mpox in humans.

Five years before the 2022-2023 global mpox outbreak Nigeria reported its first cases in nearly 40 years, with the ongoing epidemic since driven by sustained human-to-human transmission. However, limited genomic data has left questions about the timing and origin of the mpox virus' (MPXV) emergence. Here we generated 112 MPXV genomes from Nigeria from 2021-2023. We identify the closest zoonotic outgroup to the human epidemic in southern Nigeria, and estimate that the lineage transmitting from human-to-human emerged around July 2014, circulating cryptically until detected in September 2017. The epidemic originated in Southern Nigeria, particularly Rivers State, which also acted as a persistent and dominant source of viral dissemination to other states. We show that APOBEC3 activity increased MPXV's evolutionary rate twenty-fold during human-to-human transmission. We also show how Delphy, a tool for near-real-time Bayesian phylogenetics, can aid rapid outbreak analytics. Our study sheds light on MPXV's establishment in West Africa before the 2022-2023 global outbreak and highlights the need for improved pathogen surveillance and response.

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.

BACKGROUND: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. METHODS: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. RESULTS: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. CONCLUSIONS: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

Molecular epidemiology of recurrent zoonotic transmission of mpox virus in West Africa.

Nigeria and Cameroon reported their first mpox cases in over three decades in 2017 and 2018 respectively. The outbreak in Nigeria is recognised as an ongoing human epidemic. However, owing to sparse surveillance and genomic data, it is not known whether the increase in cases in Cameroon is driven by zoonotic or sustained human transmission. Notably, the frequency of zoonotic transmission remains unknown in both Cameroon and Nigeria. To address these uncertainties, we investigated the zoonotic transmission dynamics of the mpox virus (MPXV) in Cameroon and Nigeria, with a particular focus on the border regions. We show that in these regions mpox cases are still driven by zoonotic transmission of a newly identified Clade IIb.1. We identify two distinct zoonotic lineages that circulate across the Nigeria-Cameroon border, with evidence of recent and historic cross border dissemination. Our findings support that the complex cross-border forest ecosystems likely hosts shared animal populations that drive cross-border viral spread, which is likely where extant Clade IIb originated. We identify that the closest zoonotic outgroup to the human epidemic circulated in southern Nigeria in October 2013. We also show that the zoonotic precursor lineage circulated in an animal population in southern Nigeria for more than 45 years. This supports findings that southern Nigeria was the origin of the human epidemic. Our study highlights the ongoing MPXV zoonotic transmission in Cameroon and Nigeria, underscoring the continuous risk of MPXV (re)emergence.

Pleiotropic brain function of whirlin identified by a novel mutation.

Despite some evidence indicating diverse roles of whirlin in neurons, the functional corollary of whirlin gene function and behavior has not been investigated or broadly characterized. A single nucleotide variant was identified from our recessive ENU-mutagenesis screen at a donor-splice site in whirlin, a protein critical for proper sensorineural hearing function. The mutation (head-bob, hb) led to partial intron-retention causing a frameshift and introducing a premature termination codon. Mutant mice had a head-bobbing phenotype and significant hyperactivity across several phenotyping tests. Lack of complementation of head-bob with whirler mutant mice confirmed the head-bob mutation as functionally distinct with compound mutants having a mild-moderate hearing defect. Utilizing transgenics, we demonstrate rescue of the hyperactive phenotype and combined with the expression profiling data conclude whirlin plays an essential role in activity-related behaviors. These results highlight a pleiotropic role of whirlin within the brain and implicate alternative, central mediated pathways in its function.

A positive yet complicated case of gender-based violence coordination: a qualitative study of Lebanon's protracted humanitarian emergency, 2012-22.

Gender-based violence (GBV), a global health and human rights concern, often intensifies during emergencies. This paper explores the evolution of GBV coordination in Lebanon's protracted Syrian refugee crisis from 2012-22. Utilising 38 in-depth interviews and a document review, the findings were analysed using the framework for effective GBV coordination. Lebanon provides a positive yet complicated example of GBV coordination. Initially established to address the refugee crisis, it matured into a collaborative national coordination mechanism, fostering trust and advancing localisation amidst sectarian complexities. However, the volatile, restrictive policy context hindered government co-leadership and engagement with refugee-led organisations. While essential GBV response services were expanded nationwide, lack of an interagency strategy on GBV risk mitigation and prevention compromised lasting change. The paper emphasises the importance of dedicated GBV coordinators, multi-year funding, and increased attention to GBV prevention. The findings underscore the transformative potential of humanitarian responses and advocate for enhanced engagement with national stakeholders to promote sustainability in protracted crises.

Genomic surveillance during the first two years of the COVID-19 pandemic - country experience and lessons learned from Türkiye.

Background: Türkiye confirmed its first case of SARS-CoV-2 on March 11, 2020, coinciding with the declaration of the global COVID-19 pandemic. Subsequently, Türkiye swiftly increased testing capacity and implemented genomic sequencing in 2020. This paper describes Türkiye's journey of establishing genomic surveillance as a middle-income country with limited prior sequencing capacity and analyses sequencing data from the first two years of the pandemic. We highlight the achievements and challenges experienced and distill globally relevant lessons. Methods: We tracked the evolution of the COVID-19 pandemic in Türkiye from December 2020 to February 2022 through a timeline and analysed epidemiological, vaccination, and testing data. To investigate the phylodynamic and phylogeographic aspects of SARS-CoV-2, we used Nextstrain to analyze 31,629 high-quality genomes sampled from seven regions nationwide. Results: Türkiye's epidemiological curve, mirroring global trends, featured four distinct waves, each coinciding with the emergence and spread of variants of concern (VOCs). Utilizing locally manufactured kits to expand testing capacity and introducing variant-specific quantitative reverse transcription polymerase chain reaction (RT-qPCR) tests developed in partnership with a private company was a strategic advantage in Türkiye, given the scarcity and fragmented global supply chain early in the pandemic. Türkiye contributed more than 86,000 genomic sequences to global databases by February 2022, ensuring that Turkish data was reflected globally. The synergy of variant-specific RT-qPCR kits and genomic sequencing enabled cost-effective monitoring of VOCs. However, data analysis was constrained by a weak sequencing sampling strategy and fragmented data management systems, limiting the application of sequencing data to guide the public health response. Phylodynamic analysis indicated that Türkiye's geographical position as an international travel hub influenced both national and global transmission of each VOC despite travel restrictions. Conclusion: This paper provides valuable insights into the testing and genomic surveillance systems adopted by Türkiye during the COVID-19 pandemic, proposing important lessons for countries developing national systems. The findings underscore the need for robust testing and sampling strategies, streamlined sample referral, and integrated data management with metadata linkage and data quality crucial for impactful epidemiological analysis. We recommend developing national genomic surveillance strategies to guide sustainable and integrated expansion of capacities built for COVID-19 and to optimize the effective utilization of sequencing data for public health action.

FACE-Q eye module for measuring patient-reported outcomes in blepharoplasty surgery: A validation study.

This study aimed to conduct a linguistic validation of all FACE-Q eye module scales in German, and to evaluate the reliability and validity of the scales in patients with blepharoplasty. According to international recommendations, all FACE-Q scales and checklists were translated from English to German. Psychometric testing of blepharoplasty surgery-related scales of translated versions were administered to patients with blepharochalasis or dermatochalasis and a history of blepharoplasty surgery (n = 64; 11 scales) or no history of blepharoplasty surgery (n = 65; seven scales), and to a group of control subjects (n = 64; seven scales). Most of the subscales showed acceptable internal consistency, with Cronbach's alphas ranging from 0.75 to 0.97. Intraclass correlation coefficients were high (0.70-0.92), indicating good reliability, with total values of 0.63 (95% CI 0.46-0.76) and 0.68 (95% CI 0.53-0.80) for the upper eyelid and social function scores, respectively. There was good discriminability between pre- and post-blepharoplasty patients and normal subjects (p < 0.05). The German-language version of the FACE-Q eye module is a successfully validated and helpful tool for assessing outcomes after blepharoplasty surgery, especially with respect to 'satisfaction with overall facial appearance', 'psychological well-being, social function', 'decision satisfaction, outcome satisfaction', and 'early-life impact recovery'.

Dynamic Measurement and Analysis of Upper Eyelid Changes Using Ultrasound Biomicroscopy.

PURPOSE: To define the regular upper eyelid anatomy and their changes during dynamic motion using ultrasonographically depicted structures. DESIGN: A cross-sectional study. METHODS: High-resolution ultrasound biomicroscopy (50MHz) was performed on 84 upper eyelids of 42 healthy volunteers without evidence of eyelid conditions. The skin-orbicularis oculi complex (SOOC), levator aponeurosis, and Müller's muscle-conjunctival complex were imaged. The thickness of these structures was measured in primary gaze and downgaze positions. RESULTS: SOOC and levator aponeurosis thickness was bigger with eyes open than with eyes closed (p < 0.01). With eyes closed, the thickness of SOOC on the pupillary midline and levator aponeurosis was positively correlated with age (p < 0.05, p < 0.01, respectively), and the thickness of levator aponeurosis and SOOC on the pupil midline was also positively correlated with BMI index (p < 0.05). Similarly, SOOC thickness on the medial and lateral canthus line is also positively correlated with BMI index and age (p < 0.05, p < 0.01, respectively). As for the differences between genders, the mean thickness of SOOC and levator aponeurosis was statistically different (p < 0.05, respectively). The magnitude of levator aponeurosis thickness in men varied more than in women in different ocular positions (p < 0.05). All measurements had an intramethod between 0.624 and 0.792, and inter-rater ICC and intrarater ICC between 0.748 and 0.850. CONCLUSIONS: Ultrasound biomicroscopy represents a noninvasive tool for the visualization of upper eyelid morphology. Expanding its application can help to understand the dynamics of upper eyelid physiological movement, aging, and disease research in different populations and evaluate surgical outcomes.

Contemporary Surgical Management of Craniofacial Fibrous Dysplasia Using Computer-Assisted Surgery and Intraoperative Navigation.

Craniofacial fibrous dysplasia (CFD) is a rare developmental disease of bone, which typically presents as a painless, expansile mass causing deformity of the craniofacial skeleton. In rare circumstances, compression of neurovascular structures may arise, causing symptoms such as pain, visual impairment, and hearing loss. Traditionally, CFD debulking has been performed with "freehand" techniques using preoperative imaging and anthropometric norms to determine the ideal amount of tissue removal. The advent of computer-assisted surgery, computer-aided design, and computer-aided manufacturing (CAD/CAM) has revolutionized the management of CFD. Surgeons can now fabricate patient-specific osteotomy/ostectomy guides, allowing for increased accuracy in bone removal and improved cosmetic outcomes. This series of 3 cases describe our institution's technique using patient-specific ostectomy "depth guides", which allow for maximum removal of fibro-osseous tissue while sparing deep and adjacent critical structures. These techniques can be widely applied to the craniofacial skeleton to assist in the surgical management of CFD.

Periocular Asymmetry Index in Caucasian Populations Using Three-dimensional Photogrammetry Assessment.

OBJECTIVE: To quantitatively assess the periocular asymmetry and investigate its sex and age-related differences in a Caucasian population using three-dimensional (3D) stereophotogrammetry. METHOD: Standardized 3D photos of the periocular region of 301 Caucasians were taken using the VECTRA M3 3D Imaging System. Standardized landmarks were positioned, and data measurements in the periocular region were obtained from these images using VAM software and assessed using intraclass correlation coefficients (ICC) for reliability. Absolute differences and asymmetry index between the right and the left periocular region were calculated with a focus on gender and age-related differences. RESULT: Fissure height asymmetry was positively correlated with age (p < 0.01). Furthermore, reflex distance asymmetry was positively correlated with age in the elderly group (p < 0.05). Absolute differences of upper eyelid crease were 0.65 ± 0.79 mm for females and 0.90 ± 0.94 mm for males (p < 0.05). In the elderly group, the absolute differences of reflex distance were 0.664 ± 0.471 mm for males and 0.470 ± 0.408 mm for females (p < 0.05), while the absolute differences of fissure height were 0.619 ± 0.469 mm and 0.436 ± 0.372 mm, respectively (p < 0.05). All measurements had an inter-rater ICC and intra-rater ICC between 0.761 and 0.957. CONCLUSION: Periocular asymmetry is more prominent in older and male people. 3D photogrammetry is a reliable tool to detect periocular asymmetry and might provide an accurate and effective reference for periocular cosmetic, plastic, and reconstructive surgery in the clinical routine. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

Progress towards the elimination of trachoma in Nigeria.

Trachoma is targeted for elimination as a public health problem worldwide by 2030. In Nigeria, elimination activities are implemented at the local government area (LGA) level. They started in 2002 by conducting baseline population-based prevalence surveys (PBPSs), which continued in a systematic manner with engagement from the Global Trachoma Mapping Project in 2013, and subsequently Tropical Data. The results led to the development of Nigeria's first trachoma action plan and its subsequent revision with additional information. Following 449 baseline PBPSs, 122 LGAs had an active trachoma prevalence above the elimination threshold, requiring interventions, while 231 LGAs required community-based interventions for trichiasis management. By 2021, >34 million antibiotic treatments had been provided in 104 LGAs, with 89 LGAs eliminating active trachoma. Nationally, water and sanitation coverages increased by 3% and 18%, respectively, in 7 y. Systematic trichiasis case finding and management were carried out in 231 LGAs, resulting in the management of 102 527 people. Fifty-four LGAs decreased trichiasis prevalence unknown to the health system to <0.2% in persons ≥15 y of age. Where this elimination prevalence threshold was reached, trichiasis services were transitioned to routine eye/healthcare systems. Such progress relied on strong leadership and coordination from the national trachoma program and tremendous support provided by partners. Attaining elimination of trachoma as a public health problem in Nigeria by 2030 is feasible if funding support is sustained.

Intraday repeatability of macular layers measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography.

PURPOSE: To assess the intraday repeatability of macular architecture measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography (SD-OCT) and to evaluate the independence from intraindividual intraocular pressure (IOP) fluctuations. METHODS: In this single-center, time-point comparison study, 88 eyes with glaucoma, 53 eyes with ocular hypertension (OHT), and 253 healthy eyes underwent two standardized SD-OCT and intraocular pressure (IOP) measurements on the same day with a 5-h time gap. Bland-Altman plots, intraclass correlation coefficients (ICC), and random-effects model were used to analyze repeatability of entire retinal thickness, retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, and inner nuclear layer measurements. RESULTS: Intraday measurements were highly reproducible in all 3 groups. ICC were greater than 0.90, respectively. The pairwise comparisons of morphometric parameters showed a statistically significant difference (P < 0.001, respectively) between groups (glaucoma vs. control, glaucoma vs. OHT) and a significant influence of time points. No correlation was found between IOP fluctuations and morphometric parameters (P > 0.05, respectively), except for a weak positive correlation with GCL (rho = 0.109, P = 0.031). CONCLUSIONS: The evaluation of macular morphometric parameters of SD-OCT showed a high intraday repeatability and an excellent degree of agreement in glaucoma, ocular hypertension, and healthy groups. The fixed effects of time points were statistically significant. Except for a weak positive correlation of ganglion cell layer, variability did not appear to be affected by intraday IOP changes. Additional research is required to fully understand the impact of IOP fluctuations on macular morphometric parameters, considering the small observed IOP changes.

A Mixed-Methods Evaluation of Mainstreaming Mass Drug Administration for Schistosomiasis and Soil-Transmitted Helminthiasis in Four Districts of Nigeria.

In Nigeria, mass drug administration (MDA) for schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) has often been coordinated with other programs that receive greater external funding. As these programs reach stop MDA milestones, SCH and STH programs will likely need to transition implementation, or "mainstream," to domestic support. A mixed-methods study was conducted in four districts before (2021) and after (2022) mainstreaming to evaluate its impact on MDA coverage. Household surveys were done in 30 villages per district pre- and post-mainstreaming. All selected communities were eligible for STH treatment; around a third were eligible for SCH treatment. Mass drug administration was primarily conducted in schools. A total of 5,441 school-aged children were included in pre-mainstreaming and 5,789 were included in post-mainstreaming. Mass drug administration coverage was heterogeneous, but overall, mebendazole coverage declined nonsignificantly from 81% pre-mainstreaming to 76% post-mainstreaming (P = 0.09); praziquantel coverage declined significantly from 73% to 55% (P = 0.008). Coverage was significantly lower among unenrolled children or those reporting poor school attendance in nearly every survey. For the qualitative component, 173 interviews and 74 focus groups were conducted with diverse stakeholders. Respondents were deeply pessimistic about the future of MDA after mainstreaming and strongly supported a gradual transition to full government ownership. Participants formulated recommendations for effective mainstreaming: clear budget allocation by governments, robust and targeted training, trust building, and comprehensive advocacy. Although participants lacked confidence that SCH and STH programs could be sustained after reductions in external support, initial results indicate that MDA coverage can remain high 1 year into mainstreaming.

Mandating indoor air quality for public buildings.

If some countries lead by example, standards may increasingly become normalized.

Molecular characterization of non-aureus staphylococci and Mammaliicoccus from Hipposideros bats in Southwest Nigeria.

Bats are not only ecologically valuable mammals but also reservoirs of zoonotic pathogens. Their vast population, ability to fly, and inhabit diverse ecological niches could play some role in the spread of antibiotic resistance. This study investigated non-aureus staphylococci and Mammaliicoccus colonization in the Hipposideros bats at Obafemi Awolowo University, Ile-Ife, Nigeria. Pharyngeal samples (n = 23) of the insectivorous bats were analyzed, and the presumptive non-aureus staphylococcal and Mammaliicoccus isolates were confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The isolates were characterized based on antibiotic susceptibility testing and whole-genome sequencing (WGS). Six bacterial genomes were assembled, and three species were identified, including Mammaliicoccus sciuri (n = 4), Staphylococcus gallinarum (n = 1), and Staphylococcus nepalensis (n = 1). All the isolates were resistant to clindamycin, while the M. sciuri and S. gallinarum isolates were also resistant to fusidic acid. WGS analysis revealed that the M. sciuri and S. gallinarum isolates were mecA-positive. In addition, the M. sciuri isolates possessed some virulence (icaA, icaB, icaC, and sspA) genes. Multi-locus sequence typing identified two new M. sciuri sequence types (STs) 233 and ST234. The identification of these new STs in a migratory mammal deserves close monitoring because previously known ST57, ST60, and ST65 sharing ack (8), ftsZ (13), glpK (14), gmk (6), and tpiA (10) alleles with ST233 and ST234 have been linked to mastitis in animals. Moreover, the broad host range of M. sciuri could facilitate the dispersal of antibiotic resistance genes. This study provides evidence of the importance of including migratory animals in monitoring the development and spread of antibiotic resistance.

Eight weeks of exercise intervention improves visuomotor and functional capacity, performance, and physiological profile in a patient with choroidal melanoma.

The aim of this case study was to investigate the effects of an 8-wk combined exercise intervention, consisting of visual-coordinative and high-intensity interval training (HIIT), on the physical and visuomotor-functional capacity, performance, and physiological profile of a moderately active 29-yr-old man diagnosed with choroidal melanoma of the left eye. Data were collected on three occasions: at the initial diagnosis (T0), after hospitalization and radiotherapy treatment (T1), and following the recovery through the exercise intervention (T2), spanning a total of 17 wk. The primary outcome variables consisted of visuomotor and functional tests (VFTs), cardiorespiratory fitness (CRF), and microvascular circulation measured via flicker light-induced dilation (FiD). For visuomotor tests in general, a significant decline was observed between baseline T0 and T1 (by 6%-22%), followed by significant improvements at T2 (by 11%-36%), surpassing the initially observed T0 values. The cardiopulmonary exercise testing (CPET)-derived parameters exhibited a similar pattern, declining from T0 to T1 [by 8%-12% for peak V̇o2, peak power output (PO), and CPET duration, respectively], with a subsequent recovery observed in response to 8 wk of exercise training (T2), resulting in increases of 11%-25% for V̇o2, peak PO, and CPET duration. Interestingly, the dilation of both arteries and veins in response to the FiD stimulus exhibited a twofold increase compared with baseline levels. Our results suggest that the 8-wk exercise intervention improved patients' VFT and CRF profiles and exceeded baseline values. Additional investigation, particularly through randomized controlled trials, is needed to comprehensively explain changes in FiD.NEW & NOTEWORTHY Results presented here suggest that combined visual-coordinative and HIIT training improves the visual-functional capacity, performance, and physiological profile of choroidal melanoma patients during treatment recovery. This case study lays the groundwork for further research concerning exercise therapy in this unique patient population. In addition, further investigation is required to fully comprehend the combined effects of exercise and radiation therapy on vasculature and oxygenation in patients with choroidal melanoma.

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.

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.