Corpus overview


MeSH Disease

Human Phenotype


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    The Importance of Building Community Trust for Sustained Malaria MESHD Elimination Interventions During Unforeseen Major Disruptive Events Such as COVID-19: A Cambodia Case Study

    Authors: Mitra Feldman; Lieven Vernaeve; James Tibenderana; Leo Braack; Mark Debackere; Htin Kyaw Thu; Prudence Hamade; Koung Lo

    doi:10.21203/ Date: 2020-07-23 Source: ResearchSquare

    Background Impressive progress in reducing malaria MESHD trends combined with the 2018 report of no malaria MESHD related deaths MESHD for the first time, puts Cambodia well on track to reaching its malaria MESHD elimination goals. However, the novel coronavirus SARS-CoV-2 (COVID-19) pandemic presents a potential challenge to this goal. The path towards malaria MESHD elimination is dependent on sustained interventions to prevent rapid resurgence, which can quickly set back any gains achieved.Methods Mobile Malaria MESHD Workers (MMWs) need to have a strong understanding of the local geography and, most importantly, build and maintain trust among the communities they serve. To achieve this, Malaria MESHD Consortium uses a peer-to-peer approach for the MMWs and ensures the same level of trust operates between the MMWs and Malaria MESHD Consortium. Malaria MESHD Consortium’s policy during COVID-19 has been to follow national guidelines while continuing to support community-based malaria MESHD services via the MMWs / mobile malaria MESHD posts (MPs) with as minimal disruption as possible. A risk assessment was carried out by Malaria MESHD Consortium, with a mitigation plan quickly developed and implemented, to ensure MMWs were able to continue providing services without putting themselves or their patients at risk.Results Malaria MESHD Consortium ensured the MMW/ mobile MP program is built on trust, relevance to, and connection with the communities being served. An overall decline in malaria MESHD testing was reported from Health Centres and VMWs among all three provinces in March and April, not seen in previous years and possibly attributable to fear of COVID-19. However, Malaria MESHD Consortium supported MMWs have not reported any such decline in the utilization of their services and attribute this to the trust they have among the communities.Conclusion Malaria MESHD Consortium has effectively demonstrated care and solidarity with and among the MMWs and communities being served. This has ensured a high level of trust, and therefore willingness among the MMWs and communities to continue providing and utilising malaria MESHD services as usual despite the fear of COVID-19. Building trust among rural communities builds resilience and ensures uninterrupted and effective malaria MESHD elimination activities can continue even during a potential extraneous disruptive force, such as the Covid-19 pandemic.

    Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2

    Authors: Tianling Ou; Huihui Mou; Lizhou Zhang; Amrita Ojha; Hyeryun Choe; Michael Farzan

    doi:10.1101/2020.07.22.216150 Date: 2020-07-22 Source: bioRxiv

    Hydroxychloroquine, used to treat malaria MESHD and some autoimmune disorders, potently inhibits viral infection MESHD of SARS coronavirus (SARS-CoV-1) and SARS-CoV-2 in cell-culture studies. However, human clinical trials of hydroxychloroquine failed to establish its usefulness as treatment for COVID-19. This compound is known to interfere with endosomal acidification necessary to the proteolytic activity of cathepsins. Following receptor binding and endocytosis, cathepsin L can cleave the SARS-CoV-1 and SARS-CoV-2 spike (S) proteins, thereby activating membrane fusion for cell entry. The plasma SERO membrane-associated protease TMPRSS2 can similarly cleave these S proteins and activate viral entry at the cell surface. Here we show that the SARS-CoV-2 entry process is more dependent than that of SARS-CoV-1 on TMPRSS2 expression. This difference can be reversed when the furin-cleavage site of the SARS-CoV-2 S protein is ablated. We also show that hydroxychloroquine efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of hydroxychloroquine and a clinically-tested TMPRSS2 inhibitor prevents SARS-CoV-2 infection MESHD more potently than either drug alone. These studies identify functional differences between SARS-CoV-1 and -2 entry processes, and provide a mechanistic explanation for the limited in vivo utility of hydroxychloroquine as a treatment for COVID-19. Author SummaryThe novel pathogenic coronavirus SARS-CoV-2 causes COVID-19 and remains a threat to global public health. Chloroquine and hydroxychloroquine have been shown to prevent viral infection MESHD in cell-culture systems, but human clinical trials did not observe a significant improvement in COVID-19 patients treated with these compounds. Here we show that hydroxychloroquine interferes with only one of two somewhat redundant pathways by which the SARS-CoV-2 spike (S) protein is activated to mediate infection MESHD. The first pathway is dependent on the endosomal protease cathepsin L and sensitive to hydroxychloroquine, whereas the second pathway is dependent on TMPRSS2, which is unaffected by this compound. We further show that SARS-CoV-2 is more reliant than SARS coronavirus (SARS-CoV-1) on the TMPRSS2 pathway, and that this difference is due to a furin cleavage site present in the SARS-CoV-2 S protein. Finally, we show that combinations of hydroxychloroquine and a clinically tested TMPRSS2 inhibitor work together to effectively inhibit SARS-CoV-2 entry. Thus TMPRSS2 expression on physiologically relevant SARS-CoV-2 target cells may bypass the antiviral activities of hydroxychloroquine, and explain its lack of in vivo efficacy.

    Evaluation of Transmissible Plasmodium falciparum infection MESHD in transfusion medicine

    Authors: Abimbola Amoo; Hannah Dadaadegbola; John A. Olaniyi; Susan Gloria Omosa-Manyonyi; Humphrey Kariuki Njaanake

    doi:10.21203/ Date: 2020-07-13 Source: ResearchSquare

    INTRODUCTION: In sub-Saharan Africa, Malaria MESHD could lead to about 770, 000 death MESHD alone this year if COVID-19 disrupts the key strategies, according to a newly available report on WHO modeling analysis. Transfusion medicine infections MESHD are mostly prevalent studies on bacteria and viruses with very little or no effort at investigating malaria MESHD parasite infection MESHD that can cause severe post-transfusion illness, especially in transfusion-dependent patients. OBJECTIVES: This study designed to bridge the gap by screening for Plasmodium falciparum infection MESHD and determine the effect of storage duration at 4°C on P. falciparum infection MESHD. METHODOLOGY: A Cross-sectional study on blood SERO donors in Ibadan Oyo state, National blood SERO transfusion service centre. Demographic data and clinical history were obtained using a pro-formal questionnaire. Donor's blood SERO samples were P. falciparum positive using Giemsa stained microscopy. RESULTS: A total of 248 blood SERO samples collected from donors from southwest Nigeria were tested for P. falciparum parasites. The overall prevalence SERO of P. falciparum infection MESHD using Giemsa microscopy was 8.5%. The prevalence SERO in blood SERO samples stored for 3days, 7 days, and 21 days were 8.1%, 7.3%, and 5.7% respectively. There was a significant decline in the prevalence SERO of P. falciparum, by microscopy, with an increased period of blood SERO storage from day 0 to day 21 (Kendall’s Tau; p< 0.001). CONCLUSION: The present study revealed that P. falciparum is prevalent among blood SERO donors in the Ibadan, Nigeria. Blood SERO storage for about 21 days can significantly reduce the risk of transfusion-transmitted P. falciparum malaria MESHD. This can be attributed to the lack of adequate accommodation and poor sanitary conditions in the area under study. National surveillance and public health education should stop the spread of parasitic infections MESHD in transfusion medicine.

    Diagnostics and spread of SARS-CoV-2 in Western Africa: An observational laboratory-based study from Benin

    Authors: Anges Yadouleton; Anna-Lena Sander; Andres Moreira-Soto; Carine Tchibozo; Gildas Hounkanrin; Yvette Badou; Carlo Fischer; Nina Krause; Petas Akogbeto; Edmilson F. de Oliveira Filho; Anges Dossou; Sebastian Bruenink; Melchior AIssi; Mamoudou Harouna Djingarey; Benjamin Hounkpatin; Michael Nagel; Jan felix Drexler

    doi:10.1101/2020.06.29.20140749 Date: 2020-07-08 Source: medRxiv

    Information on severe acute respiratory syndrome MESHD coronavirus-2 (SARS-CoV-2) spread in Africa is limited by fragile 2 surveillance systems and insufficient diagnostic capacity. 3 We assessed the coronavirus disease MESHD-19 (COVID-19)-related diagnostic workload in Benin, Western Africa, 4 characterized SARS-CoV-2 genomes from 12 acute cases of COVID-19, used those together with public data to 5 estimate SARS-CoV-2 transmission TRANS dynamics in a Bayesian framework, validated a widely used diagnostic dual target 6 RT-PCR kit donated to African countries, and conducted serological analyses in 68 sera from confirmed COVID-19 7 cases and from febrile patients sampled before the predicted SARS-CoV-2 introduction. 8 We found a 15-fold increase in the monthly laboratory workload due to COVID-19. Genomic surveillance showed 9 introductions of three distinct SARS-CoV-2 lineages. SARS-CoV-2 genome-based analyses yielded an R0 TRANS estimate of 10 4.4 (95% confidence interval: 2.0-7.7), suggesting intense spread of SARS-CoV-2 in Africa. RT-PCR-based tests 11 were highly sensitive but showed variation of internal controls and between diagnostic targets. Commercially available 12 SARS-CoV-2 ELISAs SERO showed up to 25% false-positive results depending on antigen and antibody SERO types, likely due 13 to unspecific antibody SERO responses elicited by acute malaria MESHD according to lack of SARS-CoV-2-specific neutralizing 14 antibody SERO responses and relatively higher parasitemia MESHD in those sera. 15 We confirm an overload of the diagnostic capacity in Benin and provide baseline information on the usability of 16 genome-based surveillance in resource-limited settings. Sero-epidemiological studies SERO Sero-epidemiological studies SERO needed to assess SARS-CoV-2 17 spread may be put at stake by low specificity of tests in tropical settings globally. The increasing diagnostic challenges 18 demand continuous support of national and supranational African stakeholders.

    Dominant Factors Determining Differences of COVID-19 Fatalities Between India and Other Large-Population Regions

    Authors: Sudhakar Yarlagadda; Satyaki Kar

    id:10.20944/preprints202004.0517.v2 Date: 2020-07-05 Source:

    We analyze the Covid-19 mortality scenario in India and compare it with those in other large-population regions such as Asia-excluding-China, Africa, European Union, South America, and USA. We compare existing fatality data and offer an interpretation for low fatality based on immunity due to endemic malaria MESHD and TB. We identify the hot climate in the past summer as a possible cause for low death MESHD count in southern-hemisphere countries without endemic malaria MESHD and TB. We also make India-specific observations for easing the lockdown and estimations for the time required to attain herd immunity. Whatever optimism we present should be viewed as a guarded optimism. There should not be room for complacency.

    Connected Diagnostics to Improve Accurate Diagnosis, Treatment, and Conditional Payment of Malaria MESHD Services in Kenya.

    Authors: Shannen Van Duijn; Angela Siteyi; Sherzel Smith; Emmanuel Milimo; Leon Stijvers; Monica Oguttu; Michael Amollo; Edward Okeyo; Lilyana Dayo; Titus Kwambai; Dickens Onyango; Tobias Rinke de Wit

    doi:10.21203/ Date: 2020-06-19 Source: ResearchSquare

    Background: In sub-Saharan Africa, the material and human capacity to diagnose patients reporting with fever MESHD fever HP to healthcare providers is largely insufficient. Febrile patients are typically treated presumptively with antimalarials and/or antibiotics. Such over-prescription can lead to drug resistance and involves unnecessary costs to the health system. International funding for malaria MESHD is decreasing and transition to domestic funding is challenged by UHC efforts and recent COVID-19 outbreak. Herewith we present a digital approach to markedly improve efficiencies in diagnosis and treatment of malaria MESHD in endemic Kisumu, Kenya. The objective of this study is to evaluate feasibility, user experience, clinical performance SERO and of Connected Diagnostics in Kisumu and to assess over-prescription of antimalarials. Methods: Our intervention was performed Oct 2017 – Dec 2018 across seven providers in Kisumu. Patients were enrolled on M-TIBA platform, diagnostic test results digitized, and only positive patients were digitally entitled for malaria MESHD treatment. Data on socio-demographics, healthcare transactions and medical outcomes were analysed using standard descriptive quantitative statistics. Provider perspectives were gathered by 19 semi-structured interviews. Results: In total 11,689 febrile patients were tested. Malaria MESHD positivity rates ranged from 7.4% to 30.2% between providers, with significantly more positive cases amongst the poor (p< 0.05). Over-prescription of antimalarials was 28%, fluctuating between 4.6% to 63.3% per provider. Prescription of branded versus generic antimalarials was dichotomous. Challenges were encountered transitioning from microscopy to RDT. Conclusion: We provide full proof-of-concept of innovative Connected Diagnostics to use digitized malaria MESHD diagnostics to earmark digital entitlements for correct malaria MESHD treatment of patients. This approach has large cost-saving and quality improving potential.

    Attacking the SARS-CoV-2 Replication Machinery with the Pathogen Box’s Molecules

    Authors: Cleidy Osorio-Mogollon; Gustavo E. Olivos-Ramirez; Kewin Otazu; Manuel E. Chenet-Zuta; Georcki Ropon-Palacios; Ihosvany Camps; Gabriel M. Jimenez-Avalo; Eduardo Apari-Cossio; Natalia E. Torres-Moreira; Reyna G. Cardenas-Cardenas

    doi:10.26434/chemrxiv.12501791.v1 Date: 2020-06-19 Source: ChemRxiv

    The world is currently facing a pandemic caused by the new 2019 coronavirus disease MESHD (COVID-19), caused by SARS-CoV-2. Among the fundamental processes of this virus are viral transcription and replication. They allow the synthesisof genetic material and the consequent multiplication of the virus to infect other cells or organisms. These are performed by a multi-subunit machinery of various nonstructural proteins (nsp); among which the RNA-dependent RNApolymerase (RdRp or nsp12) is the most important, and, at the same time, conserved among coronaviruses. The structure of this protein (PDB ID: 6M71) was used as a target in the application of computational strategies for drugsearch, like virtual screening and molecular docking. The region considered for virtual screening has three important amino acids for protein catalysis: T680 (located in Motif A), N691 and D623 (located in Motif B), where a grid box was located. In turn, applying the concept of drug repositioning isconsidered as a quick response in the treatment of sudden outbreaks of diseases MESHD. Here, we used the Pathogen Box, a database of chemical compounds analyzed for the treatment against malaria MESHD, which were filtered under the criteria of selecting those that do not present any violation of Lipinski'sRule of Five. At the same time, the Remdesivir, Beclabuvir and Sofosbuvir drug, previously used in in silico and clinical studies for inhibition of nsp12, were used as positive controls. The results showed a Top10 potential target inhibitors, with binding energy higher than those of the positive controls, of which TCMDC-134153 and TCMDC-135052, both with -7.53 kcal/mol, present interactions with the three important residues of the nsp12 catalytic site. These proposed ligands would be used for subsequent validation by molecular dynamics, where they can beconsidered as drugs for the development of effective treatments against this new pandemic.

    Molecular Docking suggests repurposing of Brincidofovir as a potential drug targeting SARS-CoV-2 "COVID-19" ACE2 receptor and main protease

    Authors: Mostafa A. Hussien; Ahmed E.M. Abdelaziz

    doi:10.21203/ Date: 2020-06-15 Source: ResearchSquare

    The current outbreak of the highly transmittable and life-threatening treme intense respiratory disorder coronavirus 2 (SARS-CoV-2) has advanced rapidly and posed a global health emergency MESHD. Many clinical trials are now being conducted to test possible therapies. To assist, the molecular docking was applied on some selected FDA-approved drugs, previously used in epidemics, and the top ten compounds were selected. These ten well-characterized drugs, previously used to treat Malaria MESHD and Ebola infections MESHD, were screened based on their interactions with the SARS-CoV-2 ACE2 Receptor and 3C-like Protease. Compared to the other nine medicines, Brincidofovir, an ether lipid ester analog of cidofovir with potent antiviral activity, showed the highest docking scores and binding interactions. Therefore, Brincidofovir worth further investigations and clinical trials as a possible therapeutic agent for the COVID-19 disease MESHD .

    Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2

    Authors: Kyle Rosenke; Michael Jarvis; Friederike Feldmann; Benjamin Schwarz; Atsushi Okumura; Jamie Lovaglio; Greg Saturday; Patrick Hanley; Kimberly Meade-White; Brandi Williamson; Frederick Hansen; Lizzette Perez-Perez; Shanna Leventhal; Tsing-Lee Tang-Huau; Martha Nason; Julie Callison; Elaine Haddock; Dana Scott; Graham Sewell; Catherine Bosio; David Hawman; Emmie de Wit; Heinz Feldmann

    doi:10.1101/2020.06.10.145144 Date: 2020-06-11 Source: bioRxiv

    We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria MESHD dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease MESHD or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease MESHD model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease MESHD model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.One Sentence Summary Hydroxychloroquine prophylaxis/treatment showed no beneficial effect in SARS-CoV-2 hamster and macaque disease MESHD models.Competing Interest StatementThe authors have declared no competing interest.View Full Text

    The emergence of SARS-CoV-2 by an unusual genome reconstitution

    Authors: Seong-Tshool Hong; Md. Mehedi Hassan; Shirina Sharmin; Jinny Hong; Hoi-Seon Lee; Hyeon Jin Kim

    doi:10.21203/ Date: 2020-06-03 Source: ResearchSquare

    SARS-CoV-2 has been spreading remarkedly fast around the world since its emergence while the origin of the virus remains ambiguous. Here, we constructed all of the original prototype genome sequences of SARS-CoV-2 by selecting the common nucleotide among the different virus strains with species. Phylogenetic analysis on the prototype sequences showed that SARS-CoV-2 was a direct descendant of Bat-CoV and was closely related to Pan-CoV, Bat-SL-CoV, and SARS-CoV. The pairwise comparison of SARS-CoV-2 with Bat-CoV showed an unusual replacement of the motif consisting of 7 amino acids within the spike protein of SARS-CoV-2. Database searches showed that the motif originated from a surface protein of Plasmodium malariae MESHD, suggesting that the SARS-CoV-2 was emerged after acquiring the motif of the malaria MESHD surface protein.

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MeSH Disease
Human Phenotype

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