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Browsing by Author "Folarin, Onikepe"

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    Aneamia Following Artemisinin-Based Combination Treatments of Uncomplicated Plasmodium falciparum Malaria in Children: Temporal Patterns of Heamatocrit and the Use of Uncomplicated Hyperparasitemia as a Model for Evaluating Late Appearing Anaemia.
    (Chemotherapy, 2017) Folarin, Onikepe
    Background: In severe malaria, intravenous artesunate may cause delayed haemolytic anaemia but there has been little evaluation of the propensity of oral artemisinin-based combination treatments (ACTs) to cause late-appearing anaemia. Methods: The frequency of anaemia (haematocrit:total parasitaemia cleared, and mean haematocrit 5 weeks after treatment began were significantly lower in hyperparasitaemic children than in children without hyperparasitaemia, suggesting haematocrit conservation during treatment followed later by a loss of haematocrit. Asymptomatic late-appearing anaemia occurred in 6% of the children. Conclusion: Artesunate-amodiaquine and artemether-lumefantrine contribute to haematocrit conservation at high parasitaemias but may cause late-appearing anaemia.
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    Antimicrobial Activities of Extracts of Macrosphyra longistyla against Gram-Positive Oral Biofilm-Formers from School Children in Southwestern Nigeria and Toxicity Studies Using Brine Shrimps
    (2024-03-13) Folarin, Onikepe
    The world will benefit from more effective antimicrobial agents against oral conditions arising from the actions of biofilm forming bacteria. Also, infor mation is lacking on the oral biofilm-forming bacterial diversity in South western Nigeria. In this study, we isolate and characterize oral biofilm pro ducing bacteria in the oral cavities of schoolchildren in Southwestern Nigeria. We also investigate the antimicrobial properties of Macrosphyra longistyla extracts against the biofilm-formers and the toxicity of potent extracts. Sam ples were obtained from 109 schoolchildren aged 4 - 14 years from Lagos, Oyo and Osun States. Agar well diffusion technique was used in the antimi crobial susceptibility testing. Toxicity testing was done using brine shrimps (Artemia salina). Biofilm-formers in this study are Klebsiella sp., Streptococ cus sp., Staphylococcus sp., and Micrococcus sp. Ethanol leaf extracts had the highest activity against all biofilm-producing bacteria. Ethanol stem bark ex tract, which elicited activity against Klebsiella only, was found to be less toxic than the ethanol leaf extract. Staphylococcus showed >10 mm susceptibility to the ethanol and aqueous extracts of Macrosphyra longistyla. Streptococcus and Micrococcus were susceptible to the antimicrobial actions of the ethanol ic leaf extracts. Although the ethanol extracts of the leaves had lower mini mum inhibitory concentrations than the ethanol extracts of the stem bark, toxicity studies showed ethanol extracts of the stem-bark to be more toxic than the ethanol extracts of the leaves. In conclusion, ethanolic extracts of Macrosphyra longistyla show potential as sources of antimicrobials against gram-positive, oral biofilm-forming bacteria. Keywords Biofilms, Plant Extracts, Toxicity, Bacteria, Susceptibility, Antimicrobial
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    Brucellosis: A neglected tropical diseases
    (EUROPEAN JOURNAL OF MICROBIOLOGY AND INFECTIOUS DISEASES, 2024-08-05) Folarin, Onikepe
    Brucellosis is among the top neglected tropical diseases (NTDs) as recorded by the World Health Organization (WHO). It is referred to as neglected because it is poorly attended to when it comes to its prevention and control over a long period of time. Brucellosis is a zoonotic infection caused by the bacterial genus Brucella which include B. melitensis, B. abortus, B. suis, and B. canis. Animals with brucellosis are usually with a history of spontaneous abortion or infertility which invariably leads to low productivity. Brucella is transmitted from animals (cattle, dogs, swine, camels and goats) to humans through direct contact or indirect contact (ingestion of infected food products, or inhalation of aerosols). This disease has been reported as an important cause of fever of unknown origin particularly among occupationally exposed individuals. This disease is often easily misdiagnosed as other febrile syndromes such as malaria and typhoid fever. This has therefore resulted in mistreatments and underreporting. Brucellosis can be diagnosed through culturing, serological techniques, and most importantly through molecular techniques. This will enable adequate and correct treatment to avoid economic loss through trial-and-error approach to treatment. The road towards achieving sustainable development goals number 3 in the areas of good health and well-being should focus more on detection, treatment, and elimination of NTDs.
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    Capturing Diverse Microbial Sequence with Comprehensive and Scalable Probe Design
    (Nature Biotechnology, 2019) Folarin, Onikepe
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    Characterization of Plasmodium falciparum Structure in Nigeria with Malaria SNPS Barcode.
    (Malaria Journal, 2018) Folarin, Onikepe
    Background: Plasmodium falciparum malaria remains a major health challenge in Nigeria despite the global decline of its incidence and mortality rates. Although signifcant progress has been made in preventing the transmission of P. falciparum and controlling the spread of the infection, there is much to be done in the area of proper monitoring, surveillance of the parasite, investigating the population dynamics and drug resistance profling of the parasite as these are important to its eventual eradication. Polymorphic loci of msp1, msp2 and/or glurp genes or microsatellites have been traditionally used to characterize P. falciparum population structure in various parts of Nigeria. The lack of standardization in the interpretation of results, as well as the inability of these methods to distinguish closely related parasites, remains a limitation of these techniques. Conversely, the recently developed 24 single nucleotide polymorphism (SNP)-based molecular barcode assay has the possibility of diferentiating between closely related parasites and ofer additional information in determining the population diversity of P. falciparum within and between parasite populations. This study is therefore aimed at defning the population diversity of P. falciparum in and between two localities in Nigeria using the SNPs barcode technique. Methods: The 24-SNP high-resolution melt (HRM) barcode assay and msp2 genotyping was used to investigate both intra and inter population diversity of the parasite population in two urban cities of Nigeria. Results: Based on SNP barcode analysis, polygenomic malaria infections were observed in 17.9% and 13.5% of population from Enugu and Ibadan, respectively, while msp2 analyses showed 21% and 19.4% polygenomic infections in Enugu and Ibadan, respectively. Low levels of genetic diversity (π) of 0.328 and 0.318 were observed in Enugu and Ibadan parasite populations, respectively, while the FST value of 0.02 (p=0.055) was obtained when the genetic divergence of both populations was considered. Conclusions: The 24-SNP barcode assay was efective in analysing P. falciparum population diversity. This study also showed that P. falciparum populations in Enugu and Ibadan had a degree of intra-population diversity, but very low divergence between the population. A low degree of polygenomic infections were also observed in the two parasite populations unlike previous years. This maybe as a result of the efect of artemisinin-based combination therapy (ACT), long-lasting insecticide-treated nets (LLITNs) and intermittent preventive treatments in the study populations.
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    Clinical Illness and Outcomes in Nigerian Children with Persistent Early Appearing Anaemia Following Initiation of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria.
    (Parasite, 2019) Folarin, Onikepe
    In non-anaemic children with malaria, early-appearing anaemia (EAA) is common following artemisininbased combination treatments (ACTs) and it may become persistent (PEAA). The factors contributing to and kinetics of resolution of the deficit in haematocrit from baseline (DIHFB) characteristic of ACTs-related PEAA were evaluated in 540 consecutive children with malaria treated with artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine. Asymptomatic PEAA occurred in 62 children. In a multiple logistic regression model, a duration of illness 3 days before presentation, haematocrit <35% before and <25% one day after treatment initiation, drug attributable fall in haematocrit 6%, and treatment with dihydroartemisinin-piperaquine independently predicted PEAA. Overall, mean DIHFB was 5.7% (95% CI 4.8–6.6) 7 days after treatment initiation and was similar for all treatments. Time to 90% reduction in DIHFB was significantly longer in artemether-lumefantrine-treated children compared with other treatments. In a one compartment model, declines in DIHFB were monoexponential with overall mean estimated half-time of 3.9 days (95% CI 2.6–5.1), Cmax of 7.6% (95% CI 6.7–8.4), and Vd of 0.17 L/kg (95% CI 0.04–0.95). In Bland-Altman analyses, overall mean anaemia recovery time (AnRT) of 17.4 days (95% CI 15.5–19.4) showed insignificant bias with 4, 5 or 6 multiples of half-time of DIHFB. Ten children after recovery from PEAA progressed to late-appearing anaemia (LAA). Progression was associated with female gender and artesunateamodiaquine treatment. Asymptomatic PEAA is common following ACTs. PEAA or its progression to LAA may have implications for case and community management of anaemia and for anaemia control efforts in sub-Saharan Africa where ACTs have become first-line antimalarials
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    Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone.
    (New England Journal of Medicine, 2014) Folarin, Onikepe
    Background Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014. Methods We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase–polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients. Results Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness (in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient. Conclusions The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.)
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    Declining Responsiveness of Childhood Plasmodium Falciparum Infections to Artemisinin-Based Combination Treatments Ten Years Following Deployment as First-Line Antimalarials in Nigeria.
    (Infectious Disease of Poverty, 2019) Folarin, Onikepe
    Background: The development and spread of artemisinin-resistant Plasmodium falciparum malaria in Greater Mekong Subregion has created impetus for continuing global monitoring of efficacy of artemisinin-based combination therapies (ACTs). This post analyses is aimed to evaluate changes in early treatment response markers 10 years after the adoption of ACTs as first-line treatments of uncomplicated falciparum malaria in Nigeria. Methods: At 14 sentinel sites in six geographical areas of Nigeria, we evaluated treatment responses in 1341 children under 5 years and in additional 360 children under 16 years with uncomplicated malaria enrolled in randomized trials of artemether-lumefantrine versus artesunate-amodiaquine at 5-year interval in 2009–2010 and 2014–2015 and at 2-year interval in 2009–2010 and 2012–2015, respectively after deployment in 2005 Results: Asexual parasite positivity 1 day after treatment initiation (APPD1) rose from 54 to 62% and 2 days after treatment initiation from 5 to 26% in 2009–2010 to 2014–2015 (P = 0.002 and P < 0.0001, respectively). Parasite clearance time increased significantly from 1.6 days (95% confidence interval [CI]: 1.55–1.64) to 1.9 days (95% CI, 1.9–2.0) and geometric mean parasite reduction ratio 2 days after treatment initiation decreased significantly from 11 000 to 4700 within the same time period (P < 0.0001 for each). Enrolment parasitaemia > 75 000 μl − 1 , haematocrit > 27% 1 day post-treatment initiation, treatment with artemether-lumefantrine and enrolment in 2014–2015 independently predicted APPD1. In parallel, KaplanMeier estimated risk of recurrent infections by day 28 rose from 8 to 14% (P = 0.005) and from 9 to 15% (P = 0.02) with artemether-lumefantrine and artesunate-amodiaquine, respectively. Mean asexual parasitaemia half-life increased significantly from 1.1 h to 1.3 h within 2 years (P < 0.0001). Conclusions: These data indicate declining parasitological responses through time to the two ACTs may be due to emergence of parasites with reduced susceptibility or decrease in immunity to the infections in these children.
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    Detection of Immunoglobulin G and/or IgM antibodies specific for Lassa virus among HIV patients in the Northwestern region of Cameroon
    (Virology Journal, 2025-04-28) Folarin, Onikepe
    Background Persons with HIV are prone to other infections. Lassa virus (LASV)coinfection with HIV is a public health concern. Viral hemorrhagic fever caused by LASV has been endemic in parts of West Africa. Clinical diagnosis has been a major challenge for effective management and control because the majority of patients are asymptomatic. As such, rapid diagnosis is desirable for prompt therapeutic intervention and the implementation of control measures. The high prevalence of LASV recorded in Nigeria, a neighboring country, places Cameroon at risk. However, the detection of LASV infection among HIV patients, which we investigated in this study, has not been carried out in Cameroon. Methods Plasma samples were obtained between December 2021 and April 2022 from 330 HIV-positive patients who provided consent. They were tested for LASV IgG and/or IgM antibodies specific for LASV nucleoprotein and/ or prefusion envelope glycoproteins via the ReLASV® Pan-Lassa Combo NP/Prefusion GP IgG/IgM ELISA Test Kit according to the manufacturer’s instructions. The data were analysed via SPSS and GraphPad. Results Analysis of these samples revealed that IgG and both IgG and IgM antibodies were detected in 2.4% (8/330) and 1.8% (6/330) of the samples, respectively. Our data revealed that both IgG and IgM antibodies do not depend (p>0.05) on age, sex, or duration of antiretroviral therapy (ART), although the prevalence was high in individuals<25 years of age, males, and those who had taken ART for <5 years. The mean ODs of both IgG (0.6 0vs 0.03) and IgM (0.88 vs. 0.04) were significantly greater (p<0.05) between LAVS-positive and LAVS-negative patients. Conclusions The finding of this study shows co-infection of HIV and Lassa Virus. The presence of LASV-specific antibodies suggests exposure to LASV. These findings have direct implications for understanding the transmission risk, mitigation, and prevention and control of LASVs in Cameroon. Our results indicate the urgent need to extend LASV surveillance if there is recurrent LASV infection in any country. Keywords Lassa virus, IgG, IgM, HIV, Cameroon
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    Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa.
    (PLoS Neglected Tropical Diseases, 2015) Folarin, Onikepe
    Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance
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    Early Rising Asexual Parasitemia in Nigerian Children Following a First Dose of Artemisinin-Based Combination Treatments of Falciparum Malaria.
    (BMC Infectious Diseases, 2017) Folarin, Onikepe
    Background: Early rising asexual parasitaemia (ERAP), initially defined as ‘an increase in the parasite count over the baseline pre-treatment level during the first 24 h of treatment’ of falciparum malaria with artemisinin derivatives is well documented, but there is no characterization of its risk factors, kinetics, molecular features or relationship to late-appearing anaemia (LAA) in acute falciparum malaria in African children following oral artemisinin-based combination therapies (ACTs). Methods: ERAP was defined as ≥5% increase in pre-treatment parasitaemia within 8 h of initiating treatment. Parasitaemia was quantified pre-treatment and 1–2 hourly for 8 h, and less frequently thereafter for 6 weeks following randomized treatment of acutely malarious children with artesunate-amodiaquine, artemetherlumefantrine or dihydroartemisinin-piperaquine. Risk factors were determined by stepwise multiple logistic regression model. Kinetics of release into and of elimination of asexual parasites and DNA clones from peripheral blood were evaluated by method of residuals and non-compartment model, respectively. Parasite population changes were evaluated morphologically and by molecular genotyping. Results: ERAP occurred in 205 of 416 children. A parasitaemia <100,000/μL and parasitaemia 1 day post-treatment initiation were independent predictors of ERAP. In children with ERAP: mean and peak time of increase in parasitaemia were 105.6% (95% CI 81–130.1) and 2.5 h (95% CI 2.2–2.7), respectively. Mean lag time, half-time and rate constant of release were 0.2 h (95% CI 0.2–0.3), 1 h (95% CI 0.9–1.1), and 0.9 h−1 (95% CI 0.8–1), respectively. Schizonts and young gametocytes were seen only in peripheral blood of few children with ERAP. In age-, gender-, baseline parasitaemia- and treatment-matched children with and without ERAP, parasite DNA clearance time and area under curve of number of DNA clones versus time were significantly higher in children with ERAP indicating peripheral retention of released parasites followed by elimination. DNA clone elimination was monoexponential. Conclusion: ERAP is common, occurs rapidly as first order process and may be due to mobilization of parasites from deep tissue following a first dose of ACTs of acute childhood falciparum malaria.
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    Ebola Virus Epidemiology and Evolution in Nigeria
    (Journal of Infectious Diseases, 2016) Folarin, Onikepe
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    Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children Ten Years Following Adoption as First-line Antimalarials.
    (2018) Folarin, Onikepe
    The efficacies of 3-day regimens of artemether–lumefantrine (AL), artesunate–amodiaquine (AA), and dihydroartemisinin–piperaquine (DHP) were evaluated in 910 children < 5 years old with uncomplicated malaria from six geographical areas of Nigeria. Parasite positivity 1 day and Kaplan–Meier estimated risk of persistent parasitemia 3 days after therapy initiation were both significantly higher, and geometric mean parasite reduction ratio 1 day after treatment initiation (PRRD1) was significantly lower in AL-treated children than in AA- and DHP-treated children. No history of fever, temperature > 38 C, enrollment parasitemia > 75,000 μL−1 , and PRRD1 < 5,000 independently predicted persistent parasitemia 1 day after treatment initiation. Parasite clearance was significantly faster and risk of reappearance of asexual parasitemia after initial clearance was significantly lower in DHP-treated children. Overall, day 42 polymerase chain reaction–corrected efficacy was 98.3% (95% confidence interval [CI]: 96.1–100) and was similar for all treatments. In a non-compartment model, declines of parasitemias were monoexponential with mean terminal elimination half-life of 1.3 hours and unimodal frequency distribution of half-lives. All treatments were well tolerated. In summary, all three treatments evaluated remain efficacious treatments of uncomplicated malaria in young Nigerian children, but DHP appears more efficacious than AL or AA.
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    Empowering African Genomics for Infectious Disease Control.
    (Genome Biology, 2014) Folarin, Onikepe
    At present, African scientists can only participate minimally in the genomics revolution that is transforming the understanding, surveillance and clinical treatment of infectious diseases. We discuss new initiatives to equip African scientists with knowledge of cutting-edge genomics tools, and build a sustainable critical mass of well-trained African infectious diseases genomics scientists
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    Enabling African Scientists for the Genomic Revolution
    (Science, 2014) Folarin, Onikepe
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    Enhanced Methods for Unbiased Deep Sequencing of Lassa and Ebola RNA Viruses from Clinical and Biological Samples.
    (Genome Biology, 2014) Folarin, Onikepe
    We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies.
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    Factors Contributing to Anaemia after Uncomplicated Falciparum Malaria in under Five Year-Old Nigerian Children Ten Years Following Adoption of Artemisinin-Based Combination Therapies as First-Line Antimalarials
    (BMC Infectious Diseases, 2017) Folarin, Onikepe
    Background: Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children. Methods: Malarious 4% were evaluated by stepwise multiple logistic regression models. Survival analysis and kinetics of DAFH were evaluated by Kaplan-Meier estimator and non-compartment model, respectively Results: Pre-treatment, 355 of 959 children were anaemic. Duration of illness >2 days and parasitaemia ≤10,000 μL −1 were independent predictors of anaemia pre-treatment. EAA occurred in 301 of 604 children. Predictors of EAA were age ≤ 15 months, history of fever pre-treatment and enrolment haematocrit ≤35%. The probabilities of progression from normal haematocrit to EAA were similar for all treatments. MAFH >4% occurred in 446 of 694 children; its predictors were anaemia pre-treatment, enrolment parasitaemia ≤50,000 μL −1 , parasitaemia one day post-treatment initiation and gametocytaemia. DAFH >4% occurred in 334 of 719 children; its predictors were history of fever pre-and fever 1 day post-treatment initiation, haematocrit ≥37%, and parasitaemia >100,000 μL −1 . In 432 children, declines in DAFH deficits were monoexponential with overall estimated half-time of 2.2d (95% CI 1.9–2.6). Area under curve of deficits in DAFH versus time and estimated half-time were significantly higher in non-anaemic children indicating greater loss of haematocrit in these children. Conclusion: After ten years of adoption of ACTs, anaemia is common pre-and early post-treatment, falls in haematocrit attributable to a single infection is high, and DAFH >4% is common and significantly lower in anaemic compared to non-anaemic Nigerian children
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    Field Evaluation of a Pan-Lassa Rapid Diagnostic Test During the 2018 Nigerian Lassa Fever Outbreak.
    (Nature Scientific Report, 2020) Folarin, Onikepe
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    Field Validation of Recombinant Antigen Immunoassays for Diagnosis of Lassa Fever
    (Scientific Report, 2018) Folarin, Onikepe
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    Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever
    (Nature microbiology, 2024-02-07) Folarin, Onikepe
    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.
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