Anti-Malarial Medications for Chemoprophylaxis
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Doxycycline and Hydroxychloroquine As Treatment for High-Risk COVID-19 Patients: Experience
medRxiv preprint doi: https://doi.org/10.1101/2020.05.18.20066902; this version posted May 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities Imtiaz Ahmad, MD, MPH, FCCP1 Mohammud Alam, MD2 Ryan Saadi, MD, MPH3,6 Saborny Mahmud4 Emily Saadi, BS5 1Allergy, Sleep & Lung Care, 21st Century Oncology, Fort Myers, FL 2Infectious Disease Specialist, Cordial Medical PC, Farmingdale, NY 3Center for Market Access and Medical Innovation, Warren, NJ 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 5 Yale University, School of Public Health, New Haven, CT 6Quantaira Health, New York, NY Corresponding author : Imtiaz Ahmad, MD, Allergy, Sleep & Lung Care, 21st Century Oncology, Fort Myers, FL. email : [email protected] NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.05.18.20066902; this version posted May 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Abstract: Importance: Patients in long-term care facilities (LTCF) are at a high-risk of contracting COVID-19 due to advanced age and multiple comorbidities. -
Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications
International Journal of Molecular Sciences Review Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications Daniel Fernández-Villa 1, Maria Rosa Aguilar 1,2 and Luis Rojo 1,2,* 1 Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas, CSIC, 28006 Madrid, Spain; [email protected] (D.F.-V.); [email protected] (M.R.A.) 2 Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-915-622-900 Received: 18 September 2019; Accepted: 7 October 2019; Published: 9 October 2019 Abstract: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications. Keywords: folic acid antagonists; antifolates; antibiotics; antibacterials; immunomodulation; sulfonamides; antimalarial 1. -
Online Supplement to Incremental Costs for Psoriasis and Psoriatic
Online supplement to Incremental Costs for Psoriasis and Psoriatic Arthritis in a Population-based Cohort in Southern Sweden: Is It All Psoriasis-attributable Morbidity? The Journal of Rheumatology, doi:10.3899/jrheum.150406 Table 1. ATC-codes used to define DMARDs and topical emollients Drug group ATC-code Generic name Biologic DMARDs L04AA24 Abatacept L04AB01 Etanercept L04AA21 Efalizumab* L04AB02 Infliximab** L04AB04 Adalimumab L04AB05 Certolizumabpegol L04AB06 Golimumab L04AC03 Anakinra L04AC05 Ustekinumab L04AC07 Tocilizumab L01XC02 Rituximab Non-biologic DMARDs A07EC01 Sulfasalazine D05BB02 Acitretin L04AA15 Leflunomid L04AD01 Ciklosporin L04AX01 Azathioprine L01BA01 Methotrexate L04AX03 M01CB01 Natriumaurotiomalat M01CB03 Auranofin P01BA01 Chloroquine P01 BA02 Hydroxychloroquine Topical emollients D05AA Tjäror D05AC01 Ditranol D05AX01 Fumarsyra D05AX02 Kalcipotriol D05AX52 Kalcipotriol + betametason D07AC01 Betametason D07CC01 Betametason + antibiotika D07AC17 Flutikason D07AC13 Mometason D07AB02 Hydrokortisonbutyrat D07AD01 Klobetasol D07AB01 Klobetason DMARD=Disease Modifying AntiRheumatic Drugs *Not on the market after 20090609 **Infliximab is given as infusion in hospitals and therefore not included in the cost component ”Drugs” in our presentation of resource use and associated costs. 1 Online supplement to Incremental Costs for Psoriasis and Psoriatic Arthritis in a Population-based Cohort in Southern Sweden: Is It All Psoriasis-attributable Morbidity? The Journal of Rheumatology, doi:10.3899/jrheum.150406 Table 2A. Mean annual -
Update Tot 30-04-2020 1. Chloroquine and Hydroxychloroquine for The
Update tot 30-04-2020 1. Chloroquine and Hydroxychloroquine for the Prevention or Treatment of Novel Coronavirus Disease (COVID-19) in Africa: Caution for Inappropriate Off-Label Use in Healthcare Settings. Abena PM, Decloedt EH, Bottieau E, Suleman F, Adejumo P, Sam-Agudu NA, et al. Am j trop med hyg. 2020. 2. Evaluation of Hydroxychloroquine Retinopathy Using Ultra-Widefield Fundus Autofluorescence: Peripheral Findings in the Retinopathy. Ahn SJ, Joung J, Lee BR. American journal of ophthalmology. 2020;209:35-44. http://dx.doi.org/10.1016/j.ajo.2019.09.008. Epub 2019 Sep 14. 3. COVID-19 research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine. Alexander PE, Debono VB, Mammen MJ, Iorio A, Aryal K, Deng D, et al. J clin epidemiol. 2020. 4. Chloroquine and Hydroxychloroquine in the Era of SARS - CoV2: Caution on Their Cardiac Toxicity. Bauman JL, Tisdale JE. Pharmacotherapy. 2020. 5. Repositioned chloroquine and hydroxychloroquine as antiviral prophylaxis for COVID-19: A protocol for rapid systematic review of randomized controlled trials. Chang R, Sun W-Z. medRxiv. 2020:2020.04.18.20071167. 6. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Colson P, Rolain J-M, Lagier J-C, Brouqui P, Raoult D. Int J Antimicrob Agents. 2020:105932-. 7. Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model. Cui C, Zhang M, Yao X, Tu S, Hou Z, Jie En VS, et al. Acta Pharmaceutica Sinica B. 2020. 8. Hydroxychloroquine; Why It Might Be Successful and Why It Might Not Be Successful in the Treatment of Covid-19 Pneumonia? Could It Be A Prophylactic Drug? Deniz O. -
Dihydropteroate Synthase Gene Mutations in Pneumocystis
Dihydropteroate Synthase Gene Mutations in Pneumocystis and Sulfa Resistance Laurence Huang,* Kristina Crothers,* Chiara Atzori,† Thomas Benfield,‡ Robert Miller,§ Meja Rabodonirina,¶ and Jannik Helweg-Larsen# Pneumocystis pneumonia (PCP) remains a major Patients who are not receiving regular medical care, as cause of illness and death in HIV-infected persons. Sulfa well as those who are not receiving or responding to anti- drugs, trimethoprim-sulfamethoxazole (TMP-SMX), and retroviral therapy or prophylaxis, are also at increased risk dapsone are mainstays of PCP treatment and prophylaxis. for PCP (2). PCP may also develop in other immunosup- While prophylaxis has reduced the incidence of PCP, its pressed populations, such as cancer patients and transplant use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, recipients. Furthermore, PCP remains a leading cause of Pneumocystis jirovecii, in a standardized culture system death among critically ill patients, despite advances in prevents routine susceptibility testing and detection of drug treatment and management (3). resistance. In other microorganisms, sulfa drug resistance The first-line treatment and prophylaxis regimen for has resulted from specific point mutations in the dihy- PCP is trimethoprim-sulfamethoxazole (TMP-SMX) (4). dropteroate synthase (DHPS) gene. Similar mutations While prophylaxis has been shown to reduce the incidence have been observed in P. jirovecii. Studies have consistent- of PCP, the widespread and long-term use of TMP-SMX in ly demonstrated a significant association between the use HIV patients has raised concerns regarding the develop- of sulfa drugs for PCP prophylaxis and DHPS gene muta- ment of resistant organisms. Even short-term exposure to tions. -
A Case of Hydroxychloroquine Induced Acute Generalized Exanthematous Pustulosis Confirmed by Accidental Oral Provocation
Ann Dermatol Vol. 22, No. 1, 2010 DOI: 10.5021/ad.2010.22.1.102 CASE REPORT A Case of Hydroxychloroquine Induced Acute Generalized Exanthematous Pustulosis Confirmed by Accidental Oral Provocation Jae-Jeong Park, M.D., Sook Jung Yun, M.D., Jee-Bum Lee, M.D., Seong-Jin Kim, M.D., Young Ho Won, M.D., Seung-Chul Lee, M.D. Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea Acute generalized exanthematous pustulosis (AGEP) is a cytosis with an elevated neutrophil count. Spontaneous clinical reaction pattern that is principally drug induced and resolution usually occurs within 15 days without sequ- this is characterized by acute, nonfollicular sterile pustules elae. AGEP is induced mostly by drugs2, and especially on a background of edematous erythema. Hydroxychlo- antibiotics3. Annual incidence of AGEP is estimated to be roquine (HCQ) has been widely used to treat rheumatic and approximately 1 to 5 cases among one million persons2. dermatologic diseases and HCQ has been reported to be an Hydroxychloroquine (HCQ, oxyklorinTM, Myungmoon uncommon cause of AGEP. A 38-year-old woman with a Pharm. Co., Korea) has an antimalarial action and this 1-year history of dermatomyositis and polyarthralgia was drug is used for the treatment of rheumatic and der- treated with HCQ due to a lack of response to a previous matologic diseases due to its immunosuppressive and medication. Three weeks after starting HCQ therapy, the anti-inflammatory effects4. HCQ has been described as a pustular skin lesion developed and then this resolved after rare cause of AGEP in the Korean medical literature5. -
A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients
DOI: 10.14744/ejmo.2021.16263 EJMO 2021;5(1):63–70 Research Article A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients Abu Taiub Mohammed Mohiuddin Chowdhury,1 Mohammad Shahbaz,2 Md Rezaul Karim,3 Jahirul Islam, Guo Dan,1 Shuixiang He1 1Department of Gastroenterology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China 2Chakoria Upazilla Health Complex, Cox’s Bazar, Bangladesh 3Biomedical Research Institute of Hubei University of Medicine, Shiyan, China 4Department of Epidemiology and Health Statistics, Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China Abstract Objectives: We investigated the outcomes of Ivermectin-Doxycycline vs. Hydroxychloroquine-Azithromycin combina- tion therapy in mild to moderate COVID19 patients. Methods: Patients were divided randomly into two groups: Ivermectin 200µgm/kg single dose + Doxycycline 100mg BID for ten days in group A, and Hydroxychloroquine 400mg for the first day, then 200mg BID for nine days + Azithro- mycin 500mg daily for five days in group B (Control group). RT-PCR for SARS-CoV-2 infection was repeated in all symp- tomatic patients on the second day onward without symptoms. Repeat PCR was done every two days onward if the result found positive. Time to the negative PCR and symptomatic recovery was measured for each group. Results: All subjects in Group A reached a negative PCR, at a mean of 8.93 days, and reached symptomatic recovery, at a mean of 5.93 days, with 55.10% symptom-free by the fifth day. In group B, 96.36% reached a negative PCR at a mean of 9.33 days and were symptoms-free at 6.99 days. -
Clindamycin Plus Quinine for Treating Uncomplicated Falciparum Malaria: a Systematic Review and Meta-Analysis Charles O Obonyo1* and Elizabeth a Juma1,2
Obonyo and Juma Malaria Journal 2012, 11:2 http://www.malariajournal.com/content/11/1/2 RESEARCH Open Access Clindamycin plus quinine for treating uncomplicated falciparum malaria: a systematic review and meta-analysis Charles O Obonyo1* and Elizabeth A Juma1,2 Abstract Background: Artemisinin-based combinations are recommended for treatment of uncomplicated falciparum malaria, but are costly and in limited supply. Clindamycin plus quinine is an alternative non-artemisinin-based combination recommended by World Health Organization. The efficacy and safety of clindamycin plus quinine is not known. This systematic review aims to assess the efficacy of clindamycin plus quinine versus other anti-malarial drugs in the treatment of uncomplicated falciparum malaria. Methods: All randomized controlled trials comparing clindamycin plus quinine with other anti-malarial drugs in treating uncomplicated malaria were included in this systematic review. Databases searched included: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. Two authors independently assessed study eligibility, extracted data and assessed methodological quality. The primary outcome measure was treatment failure by day 28. Dichotomous data was compared using risk ratio (RR), in a fixed effects model. Results: Seven trials with 929 participants were included. Clindamycin plus quinine significantly reduced the risk of day 28 treatment failure compared with quinine (RR 0.14 [95% CI 0.07 to 0.29]), quinine plus sulphadoxine- pyrimethamine (RR 0.17 [95% CI 0.06 to 0.44]), amodiaquine (RR 0.11 [95% CI 0.04 to 0.27]), or chloroquine (RR 0.11 [95% CI 0.04 to 0.29]), but had similar efficacy compared with quinine plus tetracycline (RR 0.33 [95% CI 0.01 to 8.04]), quinine plus doxycycline (RR 1.00 [95% CI 0.21 to 4.66]), artesunate plus clindamycin (RR 0.57 [95% CI 0.26 to 1.24]), or chloroquine plus clindamycin (RR 0.38 [95% CI 0.13 to 1.10]). -
The Safety and Effectiveness of Single Dose Primaquine As a P
Malaria Policy Advisory Committee Meeting 11-13 September 2012, WHO HQ Session 5 WHO Evidence Review Group: The Safety and Effectiveness of Single Dose Primaquine as a P. falciparum gametocytocide Pullman Hotel, Bangkok, Thailand, 13-15 August 2012 Meeting Report Background Deployed since the early 1950s primaquine is the most Glossary: widely used 8-aminoquinoline antimalarial drug. It has been used extensively in the radical treatment of P. vivax G6PD: Glucose-6-phosphate dehydrogenase and P. ovale malaria, and as a single dose G6PDd: G6PD deficient gametocytocide in falciparum malaria. The main limitation to its use has been haemolytic toxicity. The 8- AHA: Acute haemolytic anaemia aminoquinoline antimalarials produce dose dependent acute haemolytic anaemia (AHA) in individuals who have ACT: Artemisinin combination treatment G6PD deficiency, an inherited X-linked abnormality. The MDA: Mass drug administration prevalence of the underlying allelic genes for G6PD deficiency varies typically between 5 and 32.5 % in POC: Point of care malaria endemic areas of Asia and Africa. Use of primaquine as a gametocytocide has great potential to reduce the transmission of falciparum malaria in low transmission settings, and in particular to help contain the spread of artemisinin resistant falciparum malaria in SouthEast Asia. The World Health Organisation currently recommends addition of primaquine 0.75 mg base/kg (adult dose 45 mg) to treatment regimens for P. falciparum malaria in areas of low transmission, particularly in areas where artemisinin resistant falciparum malaria is a threat, “when the risk for G6PD deficiency is considered low or testing for deficiency is available”. Unfortunately there is often uncertainty about the prevalence and severity of G6PD deficiency, and testing for it is usually not available in these areas. -
Quinoline-Based Hybrid Compounds with Antimalarial Activity
molecules Review Quinoline-Based Hybrid Compounds with Antimalarial Activity Xhamla Nqoro, Naki Tobeka and Blessing A. Aderibigbe * Department of Chemistry, University of Fort Hare, Alice Campus, Alice 5700, Eastern Cape, South Africa; [email protected] (X.N.); [email protected] (N.T.) * Correspondence: [email protected] Received: 7 November 2017; Accepted: 11 December 2017; Published: 19 December 2017 Abstract: The application of quinoline-based compounds for the treatment of malaria infections is hampered by drug resistance. Drug resistance has led to the combination of quinolines with other classes of antimalarials resulting in enhanced therapeutic outcomes. However, the combination of antimalarials is limited by drug-drug interactions. In order to overcome the aforementioned factors, several researchers have reported hybrid compounds prepared by reacting quinoline-based compounds with other compounds via selected functionalities. This review will focus on the currently reported quinoline-based hybrid compounds and their preclinical studies. Keywords: 4-aminoquinoline; 8-aminoquinoline; malaria; infectious disease; hybrid compound 1. Introduction Malaria is a parasitic infectious disease that is a threat to approximately half of the world’s population. This parasitic disease is transmitted to humans by a female Anopheles mosquito when it takes a blood meal. Pregnant women and young children in the sub-tropical regions are more prone to malaria infection. In 2015, 214 million infections were reported, with approximately 438,000 deaths and the African region accounted for 90% of the deaths [1–3]. Malaria is caused by five parasites of the genus Plasmodium, but the majority of deaths are caused by Plasmodium falciparum and Plasmodium vivax [1,4–6]. -
REACTIONS of QUININE, CHLOROQUINE, and QUINACRINE the Synthetic Antimalarial Compounds, Chloroquine
VOL. 55, 1966 BIOCHEMISTRY: O'BRIEN, OLENICK, AND HAHN 1511 * Supported by grant no. AI-05320 VR from the U.S. Public Health Service and by grant no. B-14646 from the National Science Foundation. t Address, as of July 1, 1966: The Public Health Research Institute of the City of New York, Inc., New York. 1 Fenwick, M. L., R. L. Erikson, and R. M. Franklin, Science, 146, 527 (1964). 2 Erikson, R. L., M. L. Fenwick, and R. M. Franklin, J. Mol. Biol., 13, 399 (1965). 3 Erikson, R. L., and R. M. Franklin, Bacteriol. Rev., in press. 4Erikson, R. L., M. L. Fenwick, and R. M. Franklin, J. Mol. Biol., 10, 519 (1964). 6 Franklin, R. M., and M. L. Fenwick, unpublished observations. 6 Bernardi, G., and S. N. Timasheff, Biochem. Biophys. Res. Commun., 6, 58 (1961). 7Franklin, R. M., unpublished observations. 8 Barber, R., Biochim. Biophys. Acta, 114, 422 (1966). 9 Franklin, R. M., and N. Granboulan, J. Bacteriol., 91, 834 (1966). 10 Sinsheimer, R. L., B. Starman, C. Nagler, and S. Guthrie, J. Mol. Biol., 4, 142 (1962). 11 Spiegelman, S., I. Haruna, I. B. Holland, G. Beaudreau, and D. Mills, these PROCEEDINGS, 54, 919 (1965). 12 Gros, F., W. Gilbert, H. H. Hiatt, G. Attardi, P. F. Spahr, and J. D. Watson, in Cold Spring Harbor Symposia on Quantitative Biology, vol. 26 (1961), p. 111. 13 Shatkin, A. J., these PROCEEDINGS, 54, 1721 (1965). 14 Ammann, J., H. Delius, and P. H. Hofschneider, J. Mol. Biol., 10, 557 (1964). 15 Gesteland, R. F., and H. -
A Suitable RNA Preparation Methodology for Whole Transcriptome Shotgun Sequencing Harvested from Plasmodium Vivax‑Infected Patients Catarina Bourgard1, Stefanie C
www.nature.com/scientificreports OPEN A suitable RNA preparation methodology for whole transcriptome shotgun sequencing harvested from Plasmodium vivax‑infected patients Catarina Bourgard1, Stefanie C. P. Lopes2,3, Marcus V. G. Lacerda2,3, Letusa Albrecht1,4* & Fabio T. M. Costa1* Plasmodium vivax is a world‑threatening human malaria parasite, whose biology remains elusive. The unavailability of in vitro culture, and the difculties in getting a high number of pure parasites makes RNA isolation in quantity and quality a challenge. Here, a methodological outline for RNA‑ seq from P. vivax isolates with low parasitemia is presented, combining parasite maturation and enrichment with efcient RNA extraction, yielding ~ 100 pg.µL−1 of RNA, suitable for SMART‑Seq Ultra‑Low Input RNA library and Illumina sequencing. Unbiased coding transcriptome of ~ 4 M reads was achieved for four patient isolates with ~ 51% of transcripts mapped to the P. vivax P01 reference genome, presenting heterogeneous profles of expression among individual isolates. Amongst the most transcribed genes in all isolates, a parasite‑staged mixed repertoire of conserved parasite metabolic, membrane and exported proteins was observed. Still, a quarter of transcribed genes remain functionally uncharacterized. In parallel, a P. falciparum Brazilian isolate was also analyzed and 57% of its transcripts mapped against IT genome. Comparison of transcriptomes of the two species revealed a common trophozoite‑staged expression profle, with several homologous genes being expressed. Collectively, these results will positively impact vivax research improving knowledge of P. vivax biology. Plasmodium vivax is the most prevalent malaria parasite outside Sub-Saharan Africa, causing the most geographi- cally widespread type of malaria, placing millions of people at risk of infection 1.