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1.
PLoS One ; 18(1): e0280745, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36689456

RESUMO

BACKGROUND: After admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. METHODS: In a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n = 192) or SoC only (n = 195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. RESULTS: Adherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P = 0.063); PP 40.7% RRR, 9.6% ARR (P = 0.017); AT 43.2% RRR, 10.8% ARR (P = 0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. CONCLUSIONS: In hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.


Assuntos
COVID-19 , Humanos , Doxiciclina , SARS-CoV-2 , Hospitalização , Unidades de Terapia Intensiva , Resultado do Tratamento
2.
Genome Biol ; 24(1): 8, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650523

RESUMO

BACKGROUND: CRISPR-based toolkits have dramatically increased the ease of genome and epigenome editing. SpCas9 is the most widely used nuclease. However, the difficulty of delivering SpCas9 and inability to modulate its expression in vivo hinder its widespread adoption in large animals. RESULTS: Here, to circumvent these obstacles, a doxycycline-inducible SpCas9-expressing (DIC) pig model was generated by precise knock-in of the binary tetracycline-inducible expression elements into the Rosa26 and Hipp11 loci, respectively. With this pig model, in vivo and/or in vitro genome and epigenome editing could be easily realized. On the basis of the DIC system, a convenient Cas9-based conditional knockout strategy was devised through controlling the expression of rtTA component by tissue-specific promoter, which allows the one-step generation of germline-inherited pigs enabling in vivo spatiotemporal control of gene function under simple chemical induction. To validate the feasibility of in vivo gene mutation with DIC pigs, primary and metastatic pancreatic ductal adenocarcinoma was developed by delivering a single AAV6 vector containing TP53-sgRNA, LKB1-sgRNA, and mutant human KRAS gene into the adult pancreases. CONCLUSIONS: Together, these results suggest that DIC pig resources will provide a powerful tool for conditional in vivo genome and epigenome modification for fundamental and applied research.


Assuntos
Sistemas CRISPR-Cas , Doxiciclina , Humanos , Animais , Suínos , Doxiciclina/farmacologia , Mutação , Genoma , Edição de Genes/métodos
3.
Trials ; 24(1): 11, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600250

RESUMO

BACKGROUND: Patients presenting with acute interstitial nephritis (AIN) of unknown aetiology, probably the earliest presentation of chronic kidney disease of unknown aetiology (CKDu), have been treated with oral prednisolone and doxycycline by physicians in Sri Lanka. This trial assessed the effectiveness of prednisolone and doxycycline based on eGFR changes at 6 months in patients with AIN of unknown aetiology. METHOD: A randomized clinical trial with a 2 × 2 factorial design for patients presenting with AIN of unknown aetiology (n = 59) was enacted to compare treatments with; A-prednisolone, B-doxycycline, C-both treatments together, and D-neither. The primary outcome was a recovery of patients' presenting renal function to eGFR categories: 61-90 ml/min/1.73m2 (complete remission- CR) to 31-60 ml/min/1.73m2 (partial remission- PR) and 0-30 ml/min/1.73m2 no remission (NR) by 6 months. A secondary outcome was progression-free survival (not reaching < 30 ml/min/1.73m2 eGFR), by 6-36 months. Analysis was by intention to treat. RESULTS: Seventy patients compatible with a clinical diagnosis of AIN were biopsied for eligibility; 59 AIN of unknown aetiology were enrolled, A = 15, B = 15, C = 14 and D = 15 randomly allocated to each group. Baseline characteristics were similar between groups. The number of patients with CR, PR and NR, respectively, by 6 months, in group A 3:8:2, group B 2:8:3 and group C 8:5:0 was compared with group D 8:6:1. There were no significant differences found between groups A vs. D (p = 0.2), B vs. D (p = 0.1) and C vs. D (p = 0.4). In an exploratory analysis, progression-free survival in prednisolone-treated (A + C) arms was 0/29 (100%) in comparison to 25/30 (83%) in those not so treated (B + D) arms, and the log-rank test was p = 0.02, whereas no such difference found (p = 0.60) between doxycycline-treated (B + C) arms 27/29 (93%) vs those not so treated (A + D) arms 27/30 (90%). CONCLUSION: Prednisolone and doxycycline were not beneficial for the earliest presentation of CKDu at 6 months. However, there is a potential benefit of prednisolone on the long-term outcome of CKDu. An adequately powered steroid trial using patients reaching < 30 ml/min/1.73m2 eGFR by 3 years, as an outcome is warranted for AIN of unknown aetiology. TRIAL REGISTRATION: Sri Lanka Clinical Trial Registry SLCTR/2014/007, Registered on the 31st of March 2014.


Assuntos
Doxiciclina , Nefrite Intersticial , Prednisolona , Insuficiência Renal Crônica , Humanos , Doxiciclina/uso terapêutico , Glucocorticoides/uso terapêutico , Nefrite Intersticial/tratamento farmacológico , Prednisolona/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Sri Lanka
4.
BMC Infect Dis ; 23(1): 22, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635681

RESUMO

BACKGROUND: At present, the pathogenesis of post-treatment Lyme disease (PTLDS) is not clear, so the treatment scheme of PTLDS, especially antibiotic treatment, is still controversial. This study aims to evaluate the efficacy of antibiotics in the treatment of PTLDS using network meta-analysis (NMA). METHODS: Following PRISMA guidelines, a systematic literature search was conducted on randomized controlled trials in PubMed, EMBASE, Web of Science and Cochrane Library (the literature was published from database inception through December 16, 2022). Using random effect model and fixed effect model. STATA17.0 software was used to evaluate the quality and heterogeneity of the included research literature. RESULTS: The system included 4 randomized controlled trials (485 subjects). The network meta-analysis showed that ceftriaxone had better results than placebo [Mean = 0.87, 95% CI (0.02, 1.71)] and doxycycline [Mean = 1.01, 95% CI (0.03, 1.98)] in FSS scale scores. There was no statistical difference in FSS scale scores of other drugs after treatment. In terms of FSS score results, Ceftriaxone was the best intervention according to the SUCRA value of each treatment (97.7). The analysis of outcome indicators such as Beck Depression Inventory (BDI), Mental-health Scale and Physical-functioning scale showed that there was no statistically significant difference between the antibiotic group and placebo group. CONCLUSION: Ceftriaxone treatment may be the best choice for antibiotic treatment of PTLD, which provides useful guidance for antibiotic treatment of PTLD in the future.


Assuntos
Antibacterianos , Ceftriaxona , Doença de Lyme , Humanos , Antibacterianos/efeitos adversos , Ceftriaxona/uso terapêutico , Doxiciclina/uso terapêutico , Doença de Lyme/complicações , Doença de Lyme/tratamento farmacológico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
BMC Vet Res ; 19(1): 9, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639815

RESUMO

BACKGROUND: Despite the common use of oral group treatment in pig rearing, the magnitude of the factors influencing the homogeneity and stability of antimicrobial drugs in medicated feed and medicated drinking water are largely unknown, as well as the residual concentrations of the drugs after the end of the treatment. RESULTS: This study presents a qualitative risk assessment to estimate the magnitude of the risks for reduced homogeneity and stability, and increased residual concentrations of antimicrobial drugs in medicated feed and drinking water on the farm. Risk assessment was done using a questionnaire and farm visits (n = 52), combined with a second questionnaire, and concentrations of amoxicillin and doxycycline measured in medicated feed and water samples, each collected on 10 farms. For medicated feed, the duration of storage in the silo did not show to influence the concentration levels in a consistent trend, while the treatment duration had a low to negligible effect. A moderate to high risk was found caused by human error when preparing the medicated feed on the farm. Purchased medicated feed greatly reduces the risk of human error and drugs remain stable during the duration of treatment, while the risk of residual concentrations after the end of the treatment was estimated to be low to moderate. The feed intake variability was identified as a moderate to high risk factor. For medicated drinking water, the type of dosing pump, age of pre-solution, and human errors during the preparation of the pre-solution present a moderate to high risk on homogeneity and stability. Precipitation of the active substance in the absence of a stirrer in a drinking water tank was shown to be a low to moderate risk factor for residues after treatment. Waterline length had a weak correlation with the concentrations of the antimicrobials, while a moderate to high influence was detected for the water intake by the pigs. CONCLUSIONS: A considerable variation in drug concentration in both medicated feed and medicated drinking water was detected depending on their preparation. Therefore, it is important to know which factors influence the homogeneity and stability, and the residual concentrations after treatment.


Assuntos
Anti-Infecciosos , Água Potável , Humanos , Animais , Suínos , Doxiciclina , Amoxicilina , Ração Animal/análise , Medição de Risco
6.
Talanta ; 254: 124201, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549141

RESUMO

Tetracyclines (TCs) are a family of broad-spectrum antibiotics. During the manufacturing process or storage, epimerization of tetracyclines could occur, leading to 4-epimers which are nearly inactive. From an analytical point of view, isomers are often difficult to distinguish. Previously, four pairs of TCs (oxytetracycline, tetracycline, doxycycline, chlortetracycline and their respective 4-epimers) were differentiated by mass spectrometry (MS) through protonated ions. However, they do not follow common rules and so it is still quite difficult to differentiate between them. In order to solve this, the four pairs were differentiated in the current study by collision induced dissociation (CID) spectra of the alkali adduct ions, including lithium, sodium and potassium. In the spectra of the sodium adducts, all studied tetracyclines showed a tendency to form [M+Na-NH3]+ ions, while the 4-epimers liked to form [M+Na-NH3-H2O]+ ions. Meanwhile, energy resolved mass spectrometry (ERMS) showed that all four 4-epimers' sodium adducts had the tendency to fragment at higher energy points. In the CID spectra of lithium adducts of TCs, a similar trend was observed for three pairs, except for doxycycline. For potassium adducts, the fragmentation was found to be less discriminative. As was derived from the 3D model, the four pairs all interact with the alkali metal through the dimethyl amino group at the C-4 position. The lithium adduct species also bound through the hydroxyl group at the C-5 position. If the TCs did not have a hydroxyl group at the C-5 position, they bound with the hydroxyl group at the C-6 position. For the same TC, with an increase of the diameter of the metal ion, the loss of H2O decreased gradually. As sodium adduct ions are common during the ionization process, TCs and their 4-epimers could be differentiated rapidly by ERMS of the sodium adduct ions.


Assuntos
Lítio , Metais Alcalinos , Espectrometria de Massas por Ionização por Electrospray/métodos , Tetraciclinas/química , Doxiciclina , Metais Alcalinos/química , Íons/química , Sódio/química , Antibacterianos , Potássio
7.
Reprod Biomed Online ; 45(6): 1167-1175, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36462787

RESUMO

RESEARCH QUESTION: What is the effect of chronic endometritis on patients with infertility, the necessity of endometrial re-examination and the effect of improving chronic endometritis after one cycle of antibiotic treatment on pregnancy outcomes? DESIGN: Infertile patients (n = 4003) who underwent IVF and intracytoplasmic sperm injection treatment were included. Pregnancy outcomes of groups positive for chronic endometritis were compared with groups that were negative (group 1). Patients that were positive were divided into the chronic endometritis new biopsy group (group 2) and chronic endometritis non-re-examination group (group 3). After doxycycline treatment and re-examination, the chronic endometritis new biopsy group was divided into improved chronic endometritis group (ICE) and not-improved chronic endometritis group (NICE), and their general indicators and reproductive outcomes were compared. RESULTS: No significant difference was observed in embryo implantation, early or late pregnancy loss, ectopic pregnancy, clinical pregnancy and live birth rates between groups 2 and 3. The clinical pregnancy and live birth rates in the NICE group were significantly lower than those in the ICE group (P = 0.008 and P = 0.001, respectively). After controlling for potential confounding factors, age, average number of high-quality embryos, endometrial thickness on the day of embryo transfer and number and type of embryo transfer were factors associated with live birth rates. CONCLUSIONS: Endometrial re-examination of women with chronic endometritis treated with doxycycline had no effect on pregnancy outcomes. The first cycle of doxycycline treatment could effectively improve reproductive outcomes of women with five or more CD138+ cells/high-power field.


Assuntos
Endometrite , Infertilidade , Masculino , Gravidez , Humanos , Feminino , Doxiciclina/uso terapêutico , Antibacterianos/uso terapêutico , Endometrite/complicações , Endometrite/tratamento farmacológico , Sêmen , Biópsia , Reprodução
8.
Proc Natl Acad Sci U S A ; 119(49): e2207824119, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36454756

RESUMO

Revealing the molecular events associated with reprogramming different somatic cell types to pluripotency is critical for understanding the characteristics of induced pluripotent stem cell (iPSC) therapeutic derivatives. Inducible reprogramming factor transgenic cells or animals-designated as secondary (2°) reprogramming systems-not only provide excellent experimental tools for such studies but also offer a strategy to study the variances in cellular reprogramming outcomes due to different in vitro and in vivo environments. To make such studies less cumbersome, it is desirable to have a variety of efficient reprogrammable mouse systems to induce successful mass reprogramming in somatic cell types. Here, we report the development of two transgenic mouse lines from which 2° cells reprogram with unprecedented efficiency. These systems were derived by exposing primary reprogramming cells containing doxycycline-inducible Yamanaka factor expression to a transient interruption in transgene expression, resulting in selection for a subset of clones with robust transgene response. These systems also include reporter genes enabling easy readout of endogenous Oct4 activation (GFP), indicative of pluripotency, and reprogramming transgene expression (mCherry). Notably, somatic cells derived from various fetal and adult tissues from these 2° mouse lines gave rise to highly efficient and rapid reprogramming, with transgene-independent iPSC colonies emerging as early as 1 wk after induction. These mouse lines serve as a powerful tool to explore sources of variability in reprogramming and the mechanistic underpinnings of efficient reprogramming systems.


Assuntos
Reprogramação Celular , Doxiciclina , Animais , Camundongos , Camundongos Transgênicos , Reprogramação Celular/genética , Transgenes , Células Clonais , Doxiciclina/farmacologia
9.
Trials ; 23(1): 1033, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539810

RESUMO

BACKGROUND: Ocular rosacea is common and is often managed with long-term antibiotic treatment. Doxycycline is the most commonly selected antibiotic for the treatment of rosacea. As there is no established standard of care treatment dose for rosacea, prescribed doses of doxycycline vary widely. The FDA classifies 40 mg daily dose of doxycycline for ocular rosacea as sub-microbial in comparison to an antibiotic dose of 200 mg daily. However, this "sub-microbial" dose has never been evaluated in patients with ocular rosacea, and even the sub-microbial dose has potential to alter systemic mucosa flora. Here, we present a randomized controlled trial using RNA sequencing to fully characterize the impact of sub-microbial antibiotic dosing of doxycycline on antimicrobial resistance and bacterial composition of the ocular and gut flora. METHODS: In a triple-masked parallel randomized control trial, patients with ocular rosacea will be randomized to three arms: a 40-mg dose of doxycycline, a 200-mg antibiotic dose of doxycycline, or placebo. Collected rectal and lower eyelid samples will be compared for frequency of antimicrobial resistance genetic determinants and microbiome diversity. A subjective ocular surface disease index survey and objective tear breakup time measurement will be determined. DISCUSSION: These results will enhance our understanding of the overall systemic impact of long-term systemic sub-microbial antibiotic dosing for the treatment of chronic recurrent ocular inflammatory diseases. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.org (NCT05296837) on March 22, 2022.


Assuntos
Anti-Infecciosos , Microbioma Gastrointestinal , Rosácea , Humanos , Antibacterianos , Doxiciclina/efeitos adversos , Rosácea/diagnóstico , Rosácea/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
BMJ Case Rep ; 15(12)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36543366

RESUMO

A previously well man in his 50s returned to the UK after a trip to the Mediterranean. The day after returning he developed malaise, fevers, rigors and severe headache. He was hospitalised with sepsis, multiorgan involvement, a maculopapular rash and an eschar on each hip. Serology was positive for Rickettsia spp (spotted fever group) with a rise in titre from 1:64 to 1:1024 eight days later. Blood and tissue PCR were also positive for Rickettsia spp. He had cardiac, pulmonary, renal, ocular and neurological involvement. He completed a 14-day course of doxycycline and recovered well. This is a case of likely Mediterranean spotted fever (MSF) caused by Rickettsia conorii, which is endemic to the Mediterranean basin. We highlight the need for awareness and early treatment to prevent severe complications. This case is also the first to describe Purtscher-like retinopathy in the context of likely MSF.


Assuntos
Febre Botonosa , Exantema , Rickettsia conorii , Rickettsia , Masculino , Humanos , Febre Botonosa/complicações , Febre Botonosa/diagnóstico , Febre Botonosa/tratamento farmacológico , Doxiciclina/uso terapêutico , Exantema/complicações
11.
J Ayub Med Coll Abbottabad ; 34(4): 782-785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36566399

RESUMO

BACKGROUND: Acne vulgaris is a commonly diagnosed dermatological condition characterised by pilosebaceous unit blockage or inflammation. It may manifest as inflammatory, non-inflammatory, or a combination of the two. The acne vulgaris mostly the face of individual and chest and back of individual is also affected sometime. The aim of my research is to compare the effectiveness of topical adapalene plus oral azithromycin versus topical adapalene plus oral doxycycline in treating acne. Acne is one of most common reason compelling a patient to see dermatological advice. Our goal is to find the most effective antibiotic to produce the best outcomes with the fewest possible unwanted effect (side effects) and a maximum level of patient satisfaction. METHODS: From May 1 to October 31, 2019, a randomised control trial was performed at Dermatology department MTI Lady Reading Hospital Peshawar. Using the lottery form, all of the patients were split into 2 groups. For 12 weeks, patients in Group A were given oral doxycycline 100 mg once daily and topical adapalene, while patients in Group B were given oral azithromycin 250 mg on alternating days and topical adapalene. All patients were followed at the end of 12 weeks after start of therapy to determine the efficacy in term of clearance of at least 60% of the number of lesions from baseline. RESULTS: In Group A, 22 (59.45%) patients expressed positive results whereas in Group B, only 9 (24.32%) patients expressed positive results. p value (0.0021.). CONCLUSIONS: My data suggest that oral doxycycline 100mg in combination with adapalene gave better results as compared to oral azithromycin which was also found well-tolerated option for treatment of acne on face.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Humanos , Adapaleno/uso terapêutico , Doxiciclina/uso terapêutico , Azitromicina/uso terapêutico , Resultado do Tratamento , Acne Vulgar/tratamento farmacológico , Géis/uso terapêutico
12.
Evid Based Dent ; 23(4): 158-159, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36526844

RESUMO

Design Randomised controlled clinical trial.Data sources Not applicable.Study aims This split-mouth randomised controlled clinical trial assessed the effects of placing doxycycline hyclate (Atridox) at the implant-abutment interface on the short-term clinical outcomes of dental implants.Methods The study sample included 20 patients; each patient had two mandibular implants placed, one on either side of the mandible, resulting in a total of 40 implants placed in the study sample. At the time of final prosthesis delivery, doxycycline hyclate (Atridox 10% doxycycline hyclate) was injected at the implant-abutment interface of 20 randomly selected implants on the test side (N = 20) while no intervention was done on the control side (N = 20). The primary outcome measure was changes in pocket probing depth while secondary outcome measures included the incidence of peri-implant mucositis, bleeding on probing, and changes in marginal bone levels on mesial and distal bone aspects of the implant. The outcome measures were assessed at baseline, 3 months, 6 months and 12 months.Results The results showed favourable effects of prophylactic doxycycline application. Marginal bone levels and pocket probing depths after 6 and 12 months on the test side were less compared to the control side and these differences were statistically significant. The test side also showed fewer implants with bleeding on probing and lower risk of peri-implant mucositis after 3, 6 and 12 months.Conclusion Prophylactic placement of doxycycline hyclate may reduce peri-implant bone loss and pocket probing depths, and may also reduce the risk of peri-implant mucositis.


Assuntos
Implantes Dentários , Mucosite , Peri-Implantite , Humanos , Doxiciclina/uso terapêutico , Resultado do Tratamento , Implantação Dentária Endóssea/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
PLoS Negl Trop Dis ; 16(12): e0010591, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36542603

RESUMO

BACKGROUND: Alternative strategies are recommended to accelerate onchocerciasis elimination in problematic areas including areas where annual ivermectin (IVM) distributions are unable to interrupt transmission. The aim of this study was to accelerate progress towards elimination in the Massangam health district, West Region of Cameroon where impact evaluations demonstrated ongoing transmission of onchocerciasis infection and high microfilaria (mf) prevalence despite more than 20 years of annual IVM distribution. METHODOLOGY/PRINCIPAL FINDINGS: Parasitological, entomological, and breeding site surveys were conducted in 2015 delineating a focus of high transmission and identified three communities with high mf prevalence. Individuals in these communities were screened for mf yearly for a period of two years and those positive treated each year with doxycycline 100mg daily for five weeks. In addition, surrounding communities were given biannual IVM. Temephos-based applications were performed once a week for 10 consecutive weeks on Simulium damnosum s.l. breeding sites. Parasitological and entomological assessments were conducted after two years of implementation and findings compared with 2015 baseline. Alternative strategies accelerated progress towards elimination through a significant mf reduction (χ2: 40.1; p<0.001) from 35.7% (95%CI: 29.0-42.8) to 12.3% (95%CI, 9.0-16.4). Reductions were furthermore recorded over a longer period, with a reduction of prevalence of 29.0% under AIS in 2017-2019 compared to 14.6% with IVM in 2011-2015; and by 23.2% following the two years of alternative strategies compared to 20.3% reduction over 15 years of treatment with IVM (1996-2011). Entomological assessment demonstrates that transmission is still ongoing despite the reduction in mf which is expected in an environment with complex breeding sites and open transmission zones, i.e., where migration of flies or humans to and from neighbouring areas is common. CONCLUSION/SIGNIFICANCE: This study provides evidence that alternative strategies are feasible and effective and should be considered in areas where transmission is sustained throughout long term uninterrupted MDA with IVM. However, there is need to consider wider transmission zones, and further explore optimal timing of larviciding with treatment to impact transmission.


Assuntos
Oncocercose , Humanos , Animais , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Camarões/epidemiologia , Ivermectina/uso terapêutico , Temefós , Doxiciclina , Microfilárias
14.
PLoS One ; 17(12): e0279721, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584095

RESUMO

BACKGROUND: Louse-borne relapsing fever (LBRF) remains a cause of sporadic illness and occasional outbreaks in Ethiopia and other east African countries in overcrowded and unhygienic settings. In this article, we present clinical profiles and treatment outcome of patients treated as confirmed or probable cases of LBRF at Jimma Medical Center (JMC) in southwest Ethiopia. METHODS: Patients treated as confirmed or probable cases of LBRF at JMC during a period of May-July 2022 were prospectively followed during their course of hospital stay. All patients were evaluated with blood film for hemoparasites, complete blood count, and liver enzymes on hospital presentation. They were followed with daily clinical evaluation during their hospital stay. RESULT: Thirty-six patients were treated as cases of LBRF. All patients except one were from Jimma Main Prison in Jimma Town, Ethiopia. All the patients were male with mean age of 28.7 years (SD = 12.7). The diagnosis of LBRF was confirmed by detection of B. recurrentis in blood film of 14 (38.9%) of the patients; the rest were treated as presumptive case of LBRF. Fever, reported by all patients, and an acute onset epistaxis, 30 (83.3%), were the major reasons for healthcare visits. Twenty-two (61.1%) patients were having thrombocytopenia with a platelet count < 150,000/µL; nine (25%) of which had severe forms (<50,000/µL). All patients were treated with oral doxycycline and discharged with improvement after a mean length of hospital stay of 4.25 days (SD = 0.77), range 2-6 days. Public health emergency was activated within two days of the first cases and helped in delousing all the cases and their contacts. CONCLUSION: LBRF remains a public health problem in Ethiopia in settings with poor personal hygiene. Patients with LBRF may present with severe thrombocytopenia and life-threatening bleeding. Early detection and treatment initiation prevents outbreak propagation and improves treatment outcome.


Assuntos
Febre Recorrente , Trombocitopenia , Humanos , Masculino , Adulto , Feminino , Febre Recorrente/diagnóstico , Epistaxe , Doxiciclina/uso terapêutico , Etiópia/epidemiologia , Trombocitopenia/tratamento farmacológico
15.
J Investig Med High Impact Case Rep ; 10: 23247096221145014, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36541205

RESUMO

Rocky Mountain spotted fever (RMSF), a tick-borne illness, can cause serious illness or death even in a healthy individual. Unfortunately, this illness can be difficult to diagnose as symptoms are nonspecific and oftentimes mimic benign viral illnesses. Delayed diagnosis can be detrimental as the timing of antibiotic administration is critical to prevent associated morbidity and mortality. A careful travel and social history can sometimes provide clues to make the diagnosis. Being aware of lesser-known objective findings such as hyponatremia, neurologic derangements, transaminitis, and thrombocytopenia may help raise suspicion for the disease. This is a case of a 72-year-old woman who presented with nonspecific symptoms and hyponatremia without known tick exposure. She was eventually diagnosed with RMSF. The timing of her presentation corresponded with a surge in COVID-19 infections throughout her area of residence, which further complicated her presentation and contributed to a delayed diagnosis.


Assuntos
COVID-19 , Hiponatremia , Febre Maculosa das Montanhas Rochosas , Carrapatos , Animais , Feminino , Humanos , Idoso , Febre Maculosa das Montanhas Rochosas/diagnóstico , Febre Maculosa das Montanhas Rochosas/tratamento farmacológico , Doxiciclina , Antibacterianos/uso terapêutico
16.
Vaccimonitor (La Habana, Print) ; 31(3)sept.-dic. 2022. tab, graf
Artigo em Inglês | LILACS, CUMED | ID: biblio-1410316

RESUMO

The severe acute respiratory syndrome coronavirus 2 genetic variation must be closely monitored. Viral transmission can inevitably result from mutations in the viral genome and functional proteins that aid in the virus's adaptation to the host. This study aimed to look for mutations in the E protein and see how they affected the ligands' molecular docking. Mathematical saturation mutagenesis and other informatics techniques were used. Fourteen severe acute respiratory syndrome coronavirus 2 isolates from Iraq were selected. Doxycycline and rutin were chosen as ligands. In four strains of severe acute respiratory syndrome coronavirus 2, the N15Y mutation was detected in the envelope protein. Depending on the calculation of the amount of energy of the atoms, this mutation is critical in modifying the shape of the protein as well as increasing protein stability. In the single-chain mutation, one pocket was determined, while all pentamer chains had two pockets. The N15Y mutation altered the degree of doxycycline binding by affecting the residue of attachment of the ligands. It also altered the position of the rutin's attachment to the E protein, which has a clear impact on the virion particle(AU)


La variación genética del coronavirus 2 del síndrome respiratorio agudo severo debe ser monitoreada de cerca. La transmisión viral puede resultar inevitablemente de mutaciones en el genoma viral y proteínas funcionales que ayudan en la adaptación del virus al hospedero. Este estudio tuvo como objetivo buscar mutaciones en la proteína E y ver cómo afectaban el acoplamiento molecular de los ligandos. Se utilizó la mutagénesis de saturación matemática y otras técnicas informáticas. Se seleccionaron 14 aislamientos del coronavirus 2 del síndrome respiratorio agudo severo en Irak. Se eligieron doxiciclina y rutina como ligandos. En cuatro cepas del coronavirus 2 del síndrome respiratorio agudo severo, se detectó la mutación N15Y en la proteína de la envoltura. Dependiendo del cálculo de la cantidad de energía de los átomos, esta mutación es fundamental para modificar la forma de la proteína y aumentar la estabilidad de la proteína. En la mutación de cadena única, se determinó un bolsillo, mientras que todas las cadenas de pentámero tenían dos bolsillos. La mutación N15Y alteró el grado de unión de doxiciclina al afectar el residuo de unión de los ligandos. También alteró la posición de unión de la rutina a la proteína E, lo que tiene un claro impacto en la partícula del virión(AU)


Assuntos
Humanos , Masculino , Feminino , Doxiciclina/uso terapêutico , COVID-19/transmissão , Mutação
17.
J Vector Borne Dis ; 59(3): 298-301, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36511048

RESUMO

Mediterranean spotted fever (MSF) is a tick-borne acute endemic infectious disease caused by Rickettsia conorii. While MSF may progress asymptomatically, it may lead to clinical pictures like severe hemorrhagic fever. In this article, we are presenting an MSF case with signs of high fever, headache, nausea, weakness and generalized maculopapular rash. The diagnosis of the female patient who had a history of contact with a tick-infested dog was confirmed with her clinical and laboratory data. The clinical and laboratory findings of the patient who was given doxycycline by 200 mg/day for 7 days were improved in a short time. Rickettsia conorii serology by indirect immunofluorescence assay method confirmed the diagnosis of MSF. In cases of severe sepsis accompanied by high fever and generalized maculopapular rash where the source of the infection cannot be determined in the short term, carefully questioning exposure to ticks by considering the existing geographical, seasonal and endemic environmental factors may be life-saving in terms of early diagnosis and treatment of MSF, which may become fatal even in the absence of eschars (tache noire). The symptomatology of hemorrhagic fever associated with Rickettsia conorii may be confused with that of sepsis in clinical practice.


Assuntos
Febre Botonosa , Exantema , Sepse , Carrapatos , Feminino , Cães , Animais , Febre Botonosa/diagnóstico , Febre Botonosa/tratamento farmacológico , Febre Botonosa/complicações , Doxiciclina/uso terapêutico , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/complicações , Técnica Indireta de Fluorescência para Anticorpo
18.
Medicine (Baltimore) ; 101(45): e31576, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397409

RESUMO

RATIONALE: Lyme disease is a tick-borne disease caused by the spirochete B. burgdorferi, and patients often present with symptoms comparable to a viral-like illness. The diagnosis can be challenging given its wide range of manifestations and diagnostic testing can take days or longer. Here, we present a case of Lyme disease presenting as brachial plexopathy and meningitis. PATIENT CONCERNS: A 76-years-old male presented to a tertiary-care hospital with left arm weakness and neck pain. DIAGNOSIS: Our patient was diagnosed with Lyme neuroborreliosis and had positive serology, including enzyme immunoassay and Western blot. INTERVENTIONS: Our patient received 17 days of ceftriaxone (2g IV daily) followed by oral doxycycline (100mg bid). OUTCOMES: Over the subsequent year, our patient had eventual complete recovery in muscle strength and sensation, with slower improvement to the cervical neck and left arm pain. LESSONS: Incidence of Lyme disease is increasing in North America, and the disease has a wide range of symptoms. Lyme neuroborreliosis (LNB) is 1 presentation and can present with early or late manifestations; clinicians should maintain a high index of suspicion and begin empiric treatment in individuals with a clinical syndrome consistent with LNB. Early LNB manifestations have onset within 6 months of infection and include cranial and peripheral neuropathy, radiculitis, and aseptic meningitis; late LNB encompasses a chronic encephalomyelitis.


Assuntos
Neuropatias do Plexo Braquial , Neuroborreliose de Lyme , Meningite , Humanos , Masculino , Idoso , Neuroborreliose de Lyme/complicações , Neuroborreliose de Lyme/diagnóstico , Neuroborreliose de Lyme/tratamento farmacológico , Ontário , Doxiciclina/uso terapêutico , Neuropatias do Plexo Braquial/diagnóstico , Neuropatias do Plexo Braquial/etiologia
19.
Medicine (Baltimore) ; 101(45): e31202, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397449

RESUMO

RATIONALE: Artificial joint infection caused by Mycoplasma hominis and Ureaplasma urealyticum is rare and has not been reported. PATIENTS CONCERNS: A 59-year-old man underwent left total knee arthroplasty for 1 year of pain in the left knee joint. The indwelling urinary catheter was removed after 48 hour of the surgery. On day 8 after the surgery, the patient had fever, increased skin temperature, swelling and redness around the surgical site, and floating patella test (+). According to experience, Vancomycin, Ciprofloxacin and Linezolid were administrated. Evident decrease in C-reactive protein was observed after Linezolid administration, while there was no significant improvement in clinical symptoms. Microbiome sequencing was performed, resulting in diagnosis of positive M hominis and U urealyticum. The patient was then treated with Doxycycline in the following 3 months. During the 11-month outpatient follow-up, there was no evidence of recurrence of infection. DIAGNOSIS: Microbiome sequencing was performed, resulting in diagnosis of positive M hominis and Ureaplasma urealyticum. INTERVENTIONS: The patient recovered following with Doxycycline in the following 3 months. OUTCOMES: During the 11-month outpatient follow-up, there was no evidence of recurrence of infection. LESSONS: M hominis and U urealyticum are common pathogens of the urinary system infections but they are rare in osteoarticular infections. In cases of fever, swelling and heat pain around the surgical site, joint fluid, negative blood culture and being irresponsive to anti-bacterial agents against the cell wall, special bacteria-related infection should be highly suspected.


Assuntos
Artroplastia do Joelho , Infecções Bacterianas , Infecções por Mycoplasma , Infecções por Ureaplasma , Masculino , Humanos , Pessoa de Meia-Idade , Mycoplasma hominis , Ureaplasma urealyticum , Artroplastia do Joelho/efeitos adversos , Doxiciclina/uso terapêutico , Linezolida/uso terapêutico , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/microbiologia , Infecções por Ureaplasma/diagnóstico , Infecções por Ureaplasma/tratamento farmacológico , Infecções por Ureaplasma/microbiologia , Dor
20.
Microb Pathog ; 173(Pt A): 105865, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36332790

RESUMO

A large number of evidence showed that regulatory sRNAs could modulate antibiotic resistance and sensitivity. In this study, we used RNA-sequencing to profile sRNAs in wild type and antibiotic-resistant PAO1 selected by four antibiotics (polymyxin B, ciprofloxacin, doxycycline, and ceftriaxone). Totally, we found 113, 25, 91 and 12 differentially expressed sRNAs in polymyxin B-, ciprofloxacin-, doxycycline-, and ceftriaxone-resistant P. aeruginosa, respectively. To elucidate functions of differentially expressed sRNA, we predicated their target genes and obtained pathways enriched by their target genes. In addition, our results indicated that the downregulated sRNA spae884.1, spae3443.1, and spae5681.1 might involve in polymyxin B resistance by enhancing their target genes arnA, arnD, and arnT expression in PAO1, respectively. The upregulated sRNA spae3443.1 and spae649.2 might implicate in ciprofloxacin resistance by promoting their target gene pslK expression to increase biofilm formation in PAO1. The upregulated spae1558.1 might increase oprJ expression, as well as spae3959.1 and spae3706.1 might increase mexC expression to modulate doxycycline resistance in PAO1. The sRNA novel-N714 might involve in virulence in ceftriaxone-resistant PAO1 by activating its target gene PA1429 expression. Our study might provide bases of the underlying mechanism of sRNA in regulating antibiotic resistance of PAO1 against different antibiotics.


Assuntos
Antibacterianos , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Polimixina B/farmacologia , Ceftriaxona , Doxiciclina/farmacologia , Ciprofloxacina/farmacologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica
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