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      Combination of doxycycline, streptomycin and hydroxychloroquine for short-course treatment of brucellosis: a single-blind randomized clinical trial

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          Abstract

          Purpose

          Previous studies have shown the effect of hydroxychloroquine in the treatment and prevention of recurrence of brucellosis. The aim of this study was to compare the effect of 4 and 6 week regimen containing hydroxychloroquine in the treatment of brucellosis.

          Methods

          In a single-blind randomized clinical trial, 92 patients with acute brucellosis were randomly divided in two treatment groups who received a triple drug regimen including doxycycline, streptomycin, and hydroxychloroquine (DSH] for 4 and 6 weeks. All patients were followed up for up to 6 months. Response to treatment, relapse rate, complications, and results of serological tests were compared in both groups. Data were analyzed by SPSS software version 16.

          Results

          Of the 92 patients studied, 46 received a 4 week course and 46 received a 6 week course of therapy. There were no significant differences between the two groups in terms of age and sex distribution. The response rate, treatment failure, and relapse in the 4 week treatment group were 82.6%, 17.3%, and 7.89%, respectively, and in the 6 week treatment group were 91.3%, 8.7%, and 9.52%. The frequency of negative 2ME test at 24 weeks after treatment was 11.1% in the 4 week group and 8.7% in the 6 week group. No significant differences were found between the two groups in terms of response to treatment, treatment failure, relapse, and negative 2ME test.

          Conclusion

          The 4 week and 6 week courses of the combination of DSH are equally effective in treating brucellosis. We recommend further studies to support the use of the short-course 4 week regimen for the treatment of uncomplicated brucellosis.

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          Most cited references20

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          Is Open Access

          Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

          Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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            Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine.

            Q fever endocarditis, caused by Coxiella burnetii, is fatal in 25% to 60% of patients. Currently, treatment with a long-term tetracycline and quinolone regimen for at least 4 years is recommended, although relapses are frequent. Between January 1987 and December 1997, the reference treatment of Q fever endocarditis was compared with one of doxycycline and hydroxychloroquine sulfate. Patients were treated by conventional therapy until May 1991 and then by the new regimen. Microimmunofluorescence was used for antibody-level determination for diagnosis and follow-up. Thirty-five patients were included in the study, 26 males and 9 females. Of 14 patients treated with a doxycycline and quinolone combination, 1 died, 7 relapsed (3 were re-treated and 4 switched to the new regimen), 1 is still being treated, and 5 were considered cured using this regimen only. The mean duration of therapy for cure in this group was 55 months (median, 60 months). Twenty-one patients received the doxycycline and hydroxychloroquine regimen: 1 patient died of a surgical complication, 2 are still being treated, 17 were cured, and 1 is currently being evaluated. Two patients treated for 12 months but none of the patients treated for longer than 18 months relapsed. The mean duration of treatment in this group was 31 months (median, 26 months). No significant differences were observed between the 2 regimens in terms of death, valve surgery, or tolerance. The mortality rate for both regimens in this study was 5%. Prescription of the doxycycline and hydroxychloroquine combination for at least 18 months allows shortening of the duration of therapy and reduction in the number of relapses.
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              Systematic review of brucellosis in the Middle East: disease frequency in ruminants and humans and risk factors for human infection.

              A systematic review of studies providing frequency estimates of brucellosis in humans and ruminants and risk factors for Brucella spp. seropositivity in humans in the Middle East was conducted to collate current knowledge of brucellosis in this region. Eight databases were searched for peer-reviewed original Arabic, English, French and Persian journal articles; the search was conducted on June 2014. Two reviewers evaluated articles for inclusion based on pre-defined criteria. Of 451 research articles, only 87 articles passed the screening process and provided bacteriological and serological evidence for brucellosis in all Middle Eastern countries. Brucella melitensis and B. abortus have been identified in most countries in the Middle East, supporting the notion of widespread presence of Brucella spp. especially B. melitensis across the region. Of the 87 articles, 49 were used to provide evidence of the presence of Brucella spp. but only 11 provided new knowledge on the frequency of brucellosis in humans and ruminants or on human risk factors for seropositivity and were deemed of sufficient quality. Small ruminant populations in the region show seroprevalence values that are among the highest worldwide. Human cases are likely to arise from subpopulations occupationally exposed to ruminants or from the consumption of unpasteurized dairy products. The Middle East is in need of well-designed observational studies that could generate reliable frequency estimates needed to assess the burden of disease and to inform disease control policies.
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                Author and article information

                Contributors
                shahashemi@yahoo.com
                Journal
                Infection
                Infection
                Infection
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0300-8126
                1439-0973
                30 March 2022
                : 1-5
                Affiliations
                [1 ]GRID grid.411950.8, ISNI 0000 0004 0611 9280, Department of Infectious Diseases, , Hamadan University of Medical Sciences, ; Hamadan, Iran
                [2 ]GRID grid.411950.8, ISNI 0000 0004 0611 9280, Brucellosis Research Center, , Hamadan University of Medical Sciences, ; Hamadan, Iran
                [3 ]GRID grid.411950.8, ISNI 0000 0004 0611 9280, Department of Biostatics, School of Public Health, , Hamadan University of Medical Sciences, ; Hamadan, Iran
                [4 ]GRID grid.415927.c, ISNI 0000 0004 0612 627X, Division of Infectious Diseases, , Sina Hospital, ; Mirzadeh-Eshghi Street, 65168 Hamadan, Iran
                Author information
                http://orcid.org/0000-0001-9838-7394
                Article
                1806
                10.1007/s15010-022-01806-x
                8966606
                35353333
                3f54a7f5-f9a7-46f5-8561-3b107cd7015f
                © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2022

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 17 December 2021
                : 13 March 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004697, Hamadan University of Medical Sciences;
                Categories
                Original Paper

                Infectious disease & Microbiology
                brucellosis,treatment,hydroxychloroquine,relapse
                Infectious disease & Microbiology
                brucellosis, treatment, hydroxychloroquine, relapse

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