Treatment Of Human Brucellosis Research Articles

Investigation of LncRNAs Expression as a Potential Biomarker in the Diagnosis and Treatment of Human Brucellosis

Abstract: Long non-coding RNAs (LncRNAs) are significant contributors to bacterial infections and host defense responses, presenting a novel class of gene regulators beyond conventional protein-coding genes. This narrative review aimed to explore the involvement of LncRNAs as a potential biomarker in the diagnosis and treatment of bacterial infections, with a specific focus on Brucella infections. A comprehensive literature review was conducted to identify relevant studies examining the roles of LncRNAs in immune responses during bacterial infections, with a specific emphasis on Brucella infections. Pub- Med, Scopus and other major scientific databases were searched using relevant keywords. LncRNAs crucially regulate immune responses to bacterial infections, influencing transcription factors, proinflammatory cytokines, and immune cell behavior, with both positive and negative effects. The NF-κB pathway is a key regulator for many LncRNAs in bacterial infections. During Brucella infections, essential LncRNAs activate the innate immune response, increasing proinflammatory cytokine production and immune cell differentiation. LncRNAs are associated with human brucellosis, holding promise for screening, diagnostics, or therapeutics. Further research is needed to fully understand LncRNAs' precise functions in Brucella infection and pathogenesis. Specific LncRNAs, like IFNG-AS1 and NLRP3, are upregulated during brucellosis, while others, such as Gm28309, are downregulated, influencing immunosuppression and bacterial survival. Investigating the prognostic and therapeutic potential of Brucellarelated LncRNAs warrants ongoing investigation, including their roles in other immune cells like macrophages, dendritic cells, and neutrophils responsible for bacterial clearance. Unraveling the intricate relationship between LncRNAs and brucellosis may reveal novel regulatory mechanisms and LncRNAs' roles in infection regulation, expediting diagnostics and enhancing therapeutic strategies against Brucella infections.

Clinical Course and Treatment of Human Brucellosis in a Sample of Hospitalized Cases in Albania

Abstract Brucellosis remains a public health problem in many Mediterranean countries. In this work are presenting data of human brucellosis clinics and treatment in a sample of hospitalized patients. Methods: All patient charts at regional hospital in Gjirokastra, Albania were systematically reviewed, during the period 2016-2021. All hospitalized patients with a laboratory confirmed diagnoses of brucellosis were included in the study. Variables of interest were clinical symptoms, clinical course and treatment provided. Sub-acute brucellosis was defined as clinical persistence of 3-12 months while cases with clinical symptoms persisting for ≥12 months were defined as chronic brucellosis. Results: 79% of the 86 patients were male and residing in rural areas. Fever, profuse sweating and arthralgia were the most common clinical signs. Around 70% of the brucellosis patients showed all these three symptoms. Despite a systematic tendency for more frequent presence of high fever, increased sweating and arthralgia on younger patients we could not find statistically significant differences among demographic categories. 18.6% of cases presented persistence of clinical signs after at least 3 months from the moment of the diagnoses. Almost 7% of the cases were classified as chronic cases. 75.6% of all patients were treated with a combination of doxycycline and ceftriaxone antibiotic regime. Conclusions: The massive use of a cephalosporin in treatment of brucellosis cannot be justified and may reflect a larger problem related to population awareness and health provider attitudes concerning antibiotic use in Albania. The results of this study may assist future interventions to improve brucellosis case management at hospitals or primary health care level as well as national measures at a larger scale for control of the disease.

Clinical Profile of the Diagnosis and Treatment of Human Brucellosis in Ghindae Zonal Referral Hospital, Northern Red Sea Region, Eritrea

Medical records review was conducted using a data collection tool for all the brucellosis patients treated in Ghindae Zonal Referral Hospital from 2018 to 2020. Clinical finding along with Rose-Bengal test was used to diagnose 393 cases of brucellosis. Data were entered into Microsoft Excel and then exported to SPSS version 22 for analysis. Associations between variables were assessed using chi-square test and a p-value less than 0.05 was considered statistically significant.

Development of a CRISPR/Cas9 system against ruminant animal brucellosis

BackgroundBrucellosis, caused by several Brucella species, such as the bacterium Brucella melitensis, is considered one of the most severe zoonotic diseases worldwide. Not only does it affect ruminant animal populations, leading to a substantial financial burden for stockbreeders, but also poses severe public health issues. For almost four decades in southern Europe and elsewhere, eradication of the disease has been based on ambiguously effective programs, rendering massive sanitation of livestock urgent and indispensable. Gene therapy, which has been proved effective in the clinic, could possibly constitute an alternative option towards a permanent cure for brucellosis, by aiding in the deletion or inactivation of genes associated with the replication of Brucella within the host cells.ResultsWe infected ovine macrophages with B.melitensis, to simulate the host cell/microorganism interaction in vitro, and transduced the infected cells with CRISPR/Cas9 lentiviral vectors that target Brucella’s RNA polymerase subunit A (RpolA) or virulence-associated gene virB10 at a multiplicity of infection of 60. We demonstrate a significant decrease in the bacterial load per cell when infected cells are transduced with the RpolA vector and that the number of internalized brucellae per cell remains unaffected when macrophages are transduced with a conventional lentiviral vector expressing the green fluorescence protein, thus underlining the bactericidal effect of our CRISPR/Cas9 system.ConclusionsPending in vivo verification of our findings, overall, these results may prove critical not only for the treatment of human brucellosis, but for other infectious diseases in general.

Brucellosis in Sub-Saharan Africa: Current challenges for management, diagnosis and control

Brucellosis is a highly contagious zoonosis caused by bacteria of the genus Brucella and affecting domestic and wild mammals. In this paper, the bacteriological and serological evidence of brucellosis in Sub-Saharan Africa (SSA) and its epidemiological characteristics are discussed. The tools available for the diagnosis and treatment of human brucellosis and for the diagnosis and control of animal brucellosis and their applicability in the context of SSA are presented and gaps identified. These gaps concern mostly the need for simpler and more affordable antimicrobial treatments against human brucellosis, the development of a B. melitensis vaccine that could circumvent the drawbacks of the currently available Rev 1 vaccine, and the investigation of serological diagnostic tests for camel brucellosis and wildlife. Strategies for the implementation of animal vaccination are also discussed.

ANTIMICROBIAL SUSCEPTIBILITY PROFILE OF Brucella spp. ISOLATED IN BRAZIL

The intention of this work was to investigate the susceptibility profile of 27 Brucella strains isolated from animals in Brazil, using the E-test method with antimicrobials recommended for the treatment of human brucellosis, to monitor the activities of these antimicrobials and their potential efficacy for human brucellosis treatment. Efficiency of SE-AFLP in determining the genetic diversity of the species of Brucella and its correlation with their susceptibility profile was also evaluated. All 27 strains were susceptible to doxycycline. With the exception of one strain of B. canis and of B. abortus, all strains were susceptible to gentamicin and streptomycin. Of the wild Brucella strains tested, ten, nine and five showed reduced susceptibility to rifampicin, ceftriaxone and trimetoprim/ sulfamethoxazole, respectively. One B. abortus and three B. canis strains showed multi-resistance profiles. The strain of B. abortus was resistant to streptomycin, rifampicin and ceftriaxone. Two strains of B. canis were resistant to rifampicin, ceftriaxone and trimetoprim/sulfamethoxazole, and one strain was resistant to rifampicin, ceftriaxone, streptomycin and gentamicin. Rifampicin, in combination with doxycycline, is one of the principal antibiotics prescribed to treat human brucellosis. The occurrence of strains resistant to rifampicin and other antimicrobials must be monitored before initiating this treatment, since the resistance of these strains could be one of the causes of the failure of some brucellosis treatment. No relationship was observed between SE-AFLP profiles and regional origin of the strains; neither between SE-AFLP profiles and antimicrobial profiles.

Acute Spinal Syndrome Due to Thoracic Vertebral Brucellosis: A Case Report

Introduction: Brucellosis is a zoonotic infection caused by brucella species. It is an endemic disease in the Mediterranean region. It may affect different organ systems with osteoarticular involvement in the form of peripheral arthritis, sacroiliitis and spondylitis being the most common and serious complication of the disease and it may lead to severe and irreversible sequelae. The diagnosis of brucellosis may be delayed due to the subtle nature of the illness, and it require isolation of the bacterium from blood or tissue sample for absolute diagnosis The World Health Organization guidelines for the treatment of human brucellosis discuss two regimens, both using doxycycline for a period of six weeks, in combination with either streptomycin for two to three weeks or rifampin for six weeks. Case Presentation: We are reporting a case of a 67 year-old man with chronic mid-back pain which was misdiagnosed as muscle spasm but evolved into an acute spinal syndrome due to brucellar spondylodiscitis. Conclusion: Physicians should keep a high index of suspicion and broad differential diagnosis of brucellosis as a cause of chronic back pain in appropriate parts of the world where it is considered as endemic infection, and should tailor regimen and duration of treatment according to the severity of the disease, clinical response and brucella titers.

Brucellosis in low-income and middle-income countries.

Human brucellosis is a neglected, underrecognized infection of widespread geographic distribution. It causes acute febrile illness and a potentially debilitating chronic infection in humans, and livestock infection has substantial socioeconomic impact. This review describes new information regarding the epidemiology of brucellosis in the developing world and advances in diagnosis and treatment. The highest recorded incidence of human brucellosis occurs in the Middle East and Central Asia. Fever etiology studies demonstrate brucellosis as a cause of undifferentiated febrile illness in the developing world. Brucellosis is a rare cause of fever among returning travelers, but is more common among travelers returning from the Middle East and North Africa. Sensitive and specific rapid diagnostic tests appropriate for resource-limited settings have been validated. Randomized controlled trials demonstrate that optimal treatment for human brucellosis consists of doxycycline and an aminoglycoside. Decreasing the burden of human brucellosis requires control of animal brucellosis, but evidence to inform the design of control programs in the developing world is needed. Brucellosis causes substantial morbidity in human and animal populations. While improvements in diagnostic options for resource-limited settings and stronger evidence for optimal therapy should enhance identification and treatment of human brucellosis, prevention of human disease through control in animals remains paramount.

Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

BackgroundBrucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance.Methods and FindingsA search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified.Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05–4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81–4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63–2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future.ConclusionsAlthough the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice.

Doxycycline-rifampin versus doxycycline-rifampin-gentamicin in treatment of human brucellosis

This prospective, non-randomized trial, compared the efficacy and tolerance of a doxycycline-rifampin regimen, administered for 45 days, versus doxycycline-rifampin given for 45 days plus gentamicin for the first 7-10 days, in the treatment of human brucellosis. Of 238 patients that were initially included in the study, 181 were finally evaluated. Ninety-four were treated with the doxycycline-rifampin and 87 with the doxycycline-rifampin-gentamicin regimens. In the doxycycline-rifampin group: relapses were noted in 13 (13.8%) patients; therapeutic failures in five (5.3%); and mild adverse effects in 28 (29.8%). In the doxycycline-rifampin-gentamicin group: four (4.6%) relapsed; and five (5.7%) therapeutic failures were registered. Mild adverse effects were registered in 29 (33.3%) patients. The doxycycline-rifampin-gentamicin regimen demonstrated a significantly lower relapse rate compared to the doxycycline-rifampin combination (P = 0.034). We conclude that adding gentamicin for the first 7-10 days to the standard oral doxycycline-rifampin regimen can decrease the rate of relapses.

Comparison of the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks versus streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis: a randomized clinical trial

To compare the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks with streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis. In each arm of the study, 82 patients older than 10 years randomly received 5 mg/kg gentamicin once daily for 5 days plus 100 mg of doxycycline twice daily for 8 weeks or 1 g of streptomycin intramuscularly for 2 weeks plus the same dose of doxycycline for 45 days. Therapeutic failure and relapse in these two treatment groups were compared. This study was registered in the Iranian Registry of Clinical Trials (www.irct.ir) with registration number ID: IRCT138708191441N1. The clinical manifestations in these two groups were similar. Therapeutic failure was seen in two (2.4%) patients in the gentamicin/doxycycline group and in four (4.9%) patients in the streptomycin/doxycycline group [relative risk (RR) = 0.5, 95% confidence interval (CI) 0.09-2.66, P = 0.68]. Relapse was seen in two (2.4%) cases in the gentamicin/doxycycline group and in five (6.1%) cases in the streptomycin/doxycycline group (RR = 0.4, 95% CI 0.08-2, P = 0.44). The efficacy with the gentamicin/doxycycline regimen was 95.12% and that with the streptomycin/doxycycline regimen was 89% (RR = 1.07, 95% CI 0.98-1.17, P = 0.25). Cox regression analyses showed no differences among the two treatment groups for patients who had relapse or therapeutic failure and those who had not regarding baseline covariates such as sex, duration of disease before diagnosis, positive blood culture and focal disease. The results show that the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks is not superior to that of streptomycin for 2 weeks plus doxycycline for 45 days.

Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials

Objectives To determine and quantify differences in efficacy between treatment regimens for brucellosis.Design Systematic review and meta-analysis of randomised controlled trials assessing different antibiotic regimens and durations of treatment for...

P854 Efficacy of gentamicin for 5 days plus doxycycline for eight weeks versus streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis

P854 Efficacy of gentamicin for 5 days plus doxycycline for eight weeks versus streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis

R2317 Doxycycline and streptomycin versus doxycycline alone in the treatment of human brucellosis

R2317 Doxycycline and streptomycin versus doxycycline alone in the treatment of human brucellosis

Doxycycline–rifampicin: Physicians' inferior choice in brucellosis or how convenience reigns over science

Brucellosis treatment is based on sub-optimal, not universally implemented regimens (doxycycline-rifampicin and doxycycline-streptomycin). The authors sought to evaluate specialists' and physicians' attitude towards regimens used, non-medical aspects, and future trends in human brucellosis treatment. A questionnaire-based survey of multi-national specialists, physicians, and trainees, was conducted, questionnaire answered following lectures outlining major scientific facts about existing regimens. Responders indicated preference between the two regimens, their opinion on protracted monotherapy or triple regimens of shorter duration, awareness of disease notification and hospitalization practices. Results were evaluated in relation with professional status and experience with the disease. Although scientifically inferior to doxycycline-streptomycin, doxycycline-rifampicin is the choice regimen for 64.6% of the participants. A shorter triple regimen, but not protracted monotherapy, would be desirable (60.2% and 10.4%, respectively). Low awareness of disease-notifying status and related procedures were recorded in 53.9%. When choosing between currently acceptable brucellosis regimens, medical personnel prefer convenience, even at the cost of a slightly higher relapse percentage. Future trials should evaluate shorter triple regimens. Enhancement of awareness on the disease and its principles may increase therapeutic cost effectiveness.

Future trends in human brucellosis treatment

The global burden of human brucellosis remains enormous. Existing treatment options, largely based on experience gained > 30 years ago, are adequate but not optimal. The evolving understanding of the pathophysiology of the disease may augment in designing and evaluating alternative approaches that may prove to be superior. Current alternative approaches such as co-trimoxazole-containg regimens, should be widely evaluated as being more cost-effective. New methods of delivery such as gentamicin-loaded microparticles, neutralisation of the environment where Brucella resides and use of novel antibiotics such as tigecycline may be of importance in the future. The role of immunomodulation, widely but inconsistently applied in ‘chronic’ brucellosis, should be further evaluated in all disease stages to define if it is of any use. The development of a subcellular vaccine would be an important step forward although one has to take into account the multiple interactions between Brucella and the immune system, various technical problems and the lack of funds. Reviewing existing attempts at the development of such a vaccine, the authors conclude that a trivalent subcellular vaccine may be needed for adequate efficacy.

Efficacy of Gentamicin plus Doxycycline versus Streptomycin plus Doxycycline in the Treatment of Brucellosis in Humans

In the treatment of human brucellosis, antibiotic regimens containing an aminoglycoside are reportedly associated with fewer relapses. This prospective, randomized study employed doxycycline (100 mg administered orally twice daily for 45 days) in combination with either streptomycin (1 g administered intramuscularly daily for 14 days; the DS regimen) or gentamicin (5 mg/kg per day administered intramuscularly for 7 days; the DG regimen). Efficacy of treatment was determined by rates of failure or relapse with a follow-up period of 1 year. Ninety-seven patients with a mean age (+/- standard deviation [SD]) of 33.74+/-15.47 years and 94 patients with the a mean age (+/-SD) of 36.2+/-14.14 years were treated with regimens DG and DS, respectively (P = .277). The clinical manifestations in both groups of patients were similar with the exception of sweating, which was more common in the DG group (P = .04). Three (3.2%) of the patients in the DS group and 3 (3.1%) of patients in the DG group experienced relapse (difference, 0.1%; 95% confidence interval [CI], -4% to 5%; P = 1.0). Overall, 7 (7.4%) of the patients in the DS group and 5 (5.2%) of the patients in the DG group experienced failure of therapy or relapse (difference, 2.2%; 95% CI, -4.5% to 8.9%; P = .563). The actuarial probability for relapse at 12 months after completion of therapy was 4.3% in the DS group and 2.1% in the DG group (difference, 2.2%; 95% CI, -2.8% to 7.2%). The combination of oral doxycycline for 45 days plus intramuscular gentamicin for 7 days is equally as effective as traditional therapy using doxycycline for 45 days plus streptomycin for 14 days.

Comparison of three different combination therapies in the treatment of human brucellosis

The efficacy and tolerability of three different combination treatment regimens in human brucellosis were compared in 118 uncomplicated patients enrolled in a prospective study between May 1997 and December 2002. Brucellosis was diagnosed using standard clinical and microbiological findings. Patients with central nervous system involvement, spondylitis, endocarditis or children under 16 years of age were excluded from the study. Patients were randomly assigned to receive 400 mg of ofloxacin plus 600 mg of rifampicin (OR, n = 41), 200 mg of doxycycline plus 600 mg of rifampicin (DR, n = 45) or 1g intramuscularly streptomycin (administered for three weeks) plus 200 mg doxycycline (DS, n = 32) daily for 6 weeks. All patients were followed up at least 6 months after cessation of therapy. There was no statistical difference between the groups on relapse rates and clinical response to the treatment (P>0.05). Five patients in OR (12.8%), six patients in DR (14.3%) and three patients in DS groups (9.7%) suffered relapse. The side-effects were seen in eight (19.5%), 21 (46.7%) and eight (25.0%) patients of OR, DR and DS groups, respectively. The use of combination therapy of ofloxacin plus rifampicin for 6 weeks was found to be as effective as DR and DS. The side-effects of therapy in OR and DS groups was less severe than in the DR group.

Treatment of Human Brucellosis with Rifampin plus Minocycline

In order to evaluate the efficacy and tolerability of a high intravenous dose of rifampin plus oral minocycline (administered daily for 3 weeks) for the treatment of acute brucellosis, we retrospectively reviewed the outcome of 239 consecutive patients (135 adults and 104 children) diagnosed and treated over a 17-year period in Italy. The combination used resulted in 100% response and a relapse rate lower than 2%. Fifty-two (30 adults and 22 children) (29.8%) complained of mild adverse effects including an increase in aspartate aminotransferase (>250 IU) observed in 12 cases and considered related to rifampin and in 11 cases a reversible hyperpigmentation of the tongue attributed to minocycline. A randomized prospective comparative study should be performed to confirm our encouraging results.

Treatment of human brucellosis with netilmicin and doxycycline.

We conducted a prospective, noncomparative, multicenter study to assess the safety and efficacy of doxycycline and netilmicin in the treatment of human brucellosis. The study included 64 patients who had acute brucellosis without endocarditis or neurobrucellosis. The treatment schedule consisted of the administration of 100 mg of doxycycline (or 5 mg/[kg.d] if body weight < or = 40 kg) twice a day orally for 45 days, plus 300 mg of netilmicin (6 mg/[kg.d] if body weight < or = 50 kg) intramuscularly once daily for 7 days. Therapeutic failure was noted in 5 patients (7.7%; 95% confidence interval [CI], 2.5%-17.1%), of whom 2 had spondylitis, 1 had sacroiliitis, and 1 had a splenic abscess that required splenectomy. Relapse was noted in eight patients (12.5%; 95% CI, 5.6%-23.2%). When relapse was considered in combination with initial lack of efficacy, 13 patients (21.9%; 95% CI, 12.3%-33.9%) failed to respond to therapy. Fifteen patients (23%; 95% CI, 13.5%-35.2%) had adverse effects, and one patient (1.5%) had a treatment-limiting adverse effect. Combination therapy with netilmicin/doxycycline may be effective in treating acute brucellosis. However, prospective controlled trials must confirm these results.