Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 175
Filter
Add more filters

Complementary Medicines
Publication year range
1.
Int J Infect Dis ; 140: 104-109, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38195038

ABSTRACT

OBJECTIVES: Bacillus anthracis infection is a worldwide zoonosis that affects the most vulnerable population and has a high mortality rate without treatment, especially in non-cutaneous presentations. Cutaneous scarification is still common in some regions of the world for the treatment of certain diseases as part of traditional medicine. We describe a series of cutaneus anthrax from a rural setting in Angola where cutaneus scarification is common. CASE PRESENTATION: This is a retrospective observational study describing a series of cutaneous anthrax cases from Cubal (Angola), many of whom were treated with skin scarification before admission. A total of 26 cases were diagnosed from January 2010 to December 2018. None of the cases were confirmed and eight (30.8%) were probable cases according to the Centers for the Disease Control and Prevention anthrax case definition. The median age was 11 (4.7-30.5) years, 17 (65.4%) had lesions on the head, face, or neck and 15 (57.7%) were treated with cutaneous scarification. Nine (34.6%) patients died. Traditional cutaneous scarification was significantly associated with cutaneous superinfection, respiratory, systemic involvement, and death. CONCLUSION: Our case series points to increased complications and worse outcome of cutaneous anthrax disease if treated with skin scarification.


Subject(s)
Anthrax , Bacillus anthracis , Skin Diseases, Bacterial , Child , Humans , Angola , Anthrax/diagnosis , Anthrax/drug therapy , Anthrax/epidemiology , Anti-Bacterial Agents/therapeutic use , Skin Diseases, Bacterial/drug therapy , Skin Diseases, Bacterial/epidemiology , Skin Diseases, Bacterial/diagnosis , Retrospective Studies
2.
Altern Ther Health Med ; 29(8): 822-829, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37773648

ABSTRACT

Background: Appendicitis is a common acute abdominal disease. Traditional Chinese medicine believes that acute appendicitis is caused by the accumulation of heat and toxin, and the formation of carbuncle and pus in the colon due to stasis. Therefore, treatment should be carried out to clear heat and detoxify, clear the organs, and eliminate carbuncle. Dahuang Mudan Tang contains various traditional Chinese medicines for clearing heat and detoxifying, which can be used to treat appendicitis. This study observes the therapeutic effect of Dahuang Mudan Tang on patients undergoing laparoscopic surgery for acute appendicitis. Methods: Eight databases were searched by computer and inclusion criteria were pre determined before evaluation: (1) patients with appendicitis; (2) 18-70 years old; (3) Agree to this study and obtain randomized controlled trials at home and abroad on the combined treatment of appendicitis with caesarean section and rhubarb peony testing. Using RevMan 5.3 software, conduct a comprehensive evaluation of the cultivation quality and conduct data analysis. Results: The meta-analysis ultimately included 16 papers. They are all considered randomized controlled trials. The overall efficiency of the test unit and control unit was reported in 12 surveys. The total effective rate of the experimental group was significantly higher than that of the control group (Odds Ratio (OR): (1.16; 95% Cl: 1.11,1.20; P < .001), and the duration of bowel sounds was also significantly higher than that of the control group. Standardized mean deviation (SMD): (-7.39; 95% Cl: -8.48, -6.30; P < .01), defecation time SMD: (-1.60; 95% Cl: -2.07, -1.12; P < .01). Conclusion: Based on the total effective rate, defecation time, defecation time, CRP, IL-6, and adverse reactions of participants in this study, the combination of Dahuang Mudan Tang and laparoscopy in the treatment of appendicitis may be beneficial, which can improve clinical efficacy, inhibit inflammatory reactions, and promote postoperative recovery of patients. It is worth promoting and applying in clinical practice. However, these findings still require more high-quality research to confirm. Patients undergoing laparoscopic surgery for appendicitis were treated with Dahuang Mudan Tang combined with targeted intervention.


Subject(s)
Appendicitis , Carbuncle , Gastrointestinal Diseases , Laparoscopy , Pregnancy , Humans , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Appendicitis/drug therapy , Appendicitis/surgery , Carbuncle/surgery , Cesarean Section , Randomized Controlled Trials as Topic
3.
Zhongguo Zhen Jiu ; 43(5): 584-90, 2023 May 12.
Article in Chinese | MEDLINE | ID: mdl-37161813

ABSTRACT

To explore the methods of the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng. The medical case records data of Jiusheng was collected, the frequency statistic was analyzed based on Python3.8.6, complex network analysis was performed using Gephi9.2 software, community analysis was performed by the ancient and modern medical case cloud platform V2.3.5, and analysis and verification of correlation graph and weight graph were proceed by Neo4j3.5.25 image database. The disease systems with frequency≥10 % were surgery, ophthalmology and otorhinolaryngology, locomotor, digestive and respiratory systems. The diseases under the disease system were mainly carbuncle, arthritis, lumbar disc herniation and headache. The commonly used moxibustion methods were fumigating moxibustion, blowing moxibustion, direct moxibustion and warming acupuncture. The core prescription of points obtained by complex network analysis included Yatong point, Zhiyang(GV 9), Sanyinjiao(SP 6), Dazhui(GV 14), Zusanli(ST 36), Lingtai(GV 10), Xinshu(BL 15), Zhijian point and Hegu(LI 4), which were basically consistent with high-frequency points. A total of 6 communities were obtained by community analysis, corresponding to different diseases. Through the analysis of correlation graph, 13 pairs of strong association rule points were obtained. The correlation between Zhiyang(GV 9)-Dazhui(GV 14) and Yatong point-Lingtai(GV 10) was the strongest. The acupoints with high correlation with Yatong point were Zhiyang(GV 9), Lingtai(GV 10), Dazhui(GV 14), Zusanli(ST 36) and Sanyinjiao(SP 6). In the weight graph of the high-frequency disease system, the relationship of the first weight of the surgery system disease was fumigating moxibustion-carbuncle-Yatong point, and the relationship of the first weight of the ophthalmology and otorhinolaryngology system disease was blowing moxibustion-laryngitis-Hegu (LI 4). The results of correlation graph and weight graph are consistent with the results of data mining, which can be used as an effective way to study the knowledge base of moxibustion diagnosis and treatment in the future.


Subject(s)
Acupuncture Therapy , Carbuncle , Moxibustion , Humans , Pattern Recognition, Automated , Acupuncture Points
4.
J Ethnopharmacol ; 306: 116177, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-36681167

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia humifusa Willd., known as Di-Jin-Cao in Chinese, has long been utilized as a traditional herb for the treatment of furuncles and carbuncles mainly caused by Staphylococcus aureus infection. Despite extensive chemical and pharmacological studies reported previously for E. humifusa, the antibacterial and antibiofilm activities against S. aureus as well as the related mechanism of action (MoA) remain largely obscure. AIM OF THE STUDY: To investigate the antibacterial and antibiofilm activities of the preferred fractions and compounds from E. humifusa against S. aureus and assess the associated MoA. MATERIALS AND METHODS: The bioactive fractions and compounds were obtained from the 75% ethanol extract of E. humifusa (75%-EEEH) with the assistance of the related antibacterial and antibiofilm screening. Their antibacterial activities were determined using the broth microdilution method, whilst the inhibition of biofilm formation and the disruption of preformed biofilm were assessed by crystal violet staining and confocal laser scanning microscopy (CLSM). To achieve more effective therapies, the combinatory effects of different components were also studied. The biofilm metabolic activities of isolated compounds were evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The scanning electron microscopy (SEM) and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to explore the antibiofilm mechanism. RESULTS: Fractions DJC06 and DJC07 collected from the ethyl acetate extract of the 75%-EEEH exhibited antibacterial activity (MIC = 256 µg/mL) against S. aureus and further separation of these two fractions led to the isolation and characterization of 22 compounds. Among the isolates, luteolin (LU), quercetin (QU), and kaempferol (KA) are the verified components associated with the antibacterial and antibiofilm activities by displaying individual or combinational MIC values of 8-128 µg/mL and 70.9-99.7% inhibition for biofilm formation. Importantly, QU and KA can work in synergy with LU to significantly enhance the efficacy via destroying cell integrity, increasing membrane permeability, and down-regulating the biofilm-related gene expression. CONCLUSIONS: The preferred fractions and compounds from E. humifusa exerted desired antibacterial and antibiofilm efficacy against S. aureus via a MoA involving cell morphology disruption and altered genes expression. The findings herein not only support its traditional use in the treatment of furuncles and carbuncles, but reveal E. humifusa is a potential source for producing promising antibiofilm alternatives against S. aureus and highlight the isolated components (LU, QU, KA) that can potentiate the efficacy when used in synergy.


Subject(s)
Carbuncle , Euphorbia , Furunculosis , Staphylococcal Infections , Animals , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Staphylococcal Infections/microbiology , Biofilms , Microbial Sensitivity Tests
5.
Article in Chinese | WPRIM | ID: wpr-980763

ABSTRACT

To explore the methods of the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng. The medical case records data of Jiusheng was collected, the frequency statistic was analyzed based on Python3.8.6, complex network analysis was performed using Gephi9.2 software, community analysis was performed by the ancient and modern medical case cloud platform V2.3.5, and analysis and verification of correlation graph and weight graph were proceed by Neo4j3.5.25 image database. The disease systems with frequency≥10 % were surgery, ophthalmology and otorhinolaryngology, locomotor, digestive and respiratory systems. The diseases under the disease system were mainly carbuncle, arthritis, lumbar disc herniation and headache. The commonly used moxibustion methods were fumigating moxibustion, blowing moxibustion, direct moxibustion and warming acupuncture. The core prescription of points obtained by complex network analysis included Yatong point, Zhiyang(GV 9), Sanyinjiao(SP 6), Dazhui(GV 14), Zusanli(ST 36), Lingtai(GV 10), Xinshu(BL 15), Zhijian point and Hegu(LI 4), which were basically consistent with high-frequency points. A total of 6 communities were obtained by community analysis, corresponding to different diseases. Through the analysis of correlation graph, 13 pairs of strong association rule points were obtained. The correlation between Zhiyang(GV 9)-Dazhui(GV 14) and Yatong point-Lingtai(GV 10) was the strongest. The acupoints with high correlation with Yatong point were Zhiyang(GV 9), Lingtai(GV 10), Dazhui(GV 14), Zusanli(ST 36) and Sanyinjiao(SP 6). In the weight graph of the high-frequency disease system, the relationship of the first weight of the surgery system disease was fumigating moxibustion-carbuncle-Yatong point, and the relationship of the first weight of the ophthalmology and otorhinolaryngology system disease was blowing moxibustion-laryngitis-Hegu (LI 4). The results of correlation graph and weight graph are consistent with the results of data mining, which can be used as an effective way to study the knowledge base of moxibustion diagnosis and treatment in the future.


Subject(s)
Humans , Moxibustion , Carbuncle , Pattern Recognition, Automated , Acupuncture Therapy , Acupuncture Points
6.
Clin Infect Dis ; 75(Suppl 3): S379-S391, 2022 10 17.
Article in English | MEDLINE | ID: mdl-36251546

ABSTRACT

BACKGROUND: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. METHODS: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. RESULTS: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, ß-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. CONCLUSIONS: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.


Subject(s)
Anthrax , Anti-Infective Agents , Bacillus anthracis , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Animals , Anthrax/drug therapy , Anthrax/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/therapeutic use , Cilastatin, Imipenem Drug Combination/pharmacology , Cilastatin, Imipenem Drug Combination/therapeutic use , Ciprofloxacin/therapeutic use , Doxycycline/therapeutic use , Glycopeptides/pharmacology , Glycopeptides/therapeutic use , Humans , Levofloxacin/therapeutic use , Lipopeptides/pharmacology , Lipopeptides/therapeutic use , Models, Animal , Tetracyclines/therapeutic use , United States , beta-Lactams/therapeutic use
7.
Ann Clin Microbiol Antimicrob ; 20(1): 79, 2021 Dec 02.
Article in English | MEDLINE | ID: mdl-34856999

ABSTRACT

BACKGROUND AND OBJECTIVES: The chemotherapeutic management of infections has become challenging due to the global emergence of antibiotic resistant pathogenic bacteria. The recent expansion of studies on plant-derived natural products has lead to the discovery of a plethora of phytochemicals with the potential to combat bacterial drug resistance via various mechanisms of action. This review paper summarizes the primary antibiotic resistance mechanisms of bacteria and also discusses the antibiotic-potentiating ability of phytoextracts and various classes of isolated phytochemicals in reversing antibiotic resistance in anthrax agent Bacillus anthracis and emerging superbug bacteria. METHODS: Growth inhibitory indices and fractional inhibitory concentration index were applied to evaluate the in vitro synergistic activity of phytoextract-antibiotic combinations in general. FINDINGS: A number of studies have indicated that plant-derived natural compounds are capable of significantly reducing the minimum inhibitory concentration of standard antibiotics by altering drug-resistance mechanisms of B. anthracis and other superbug infection causing bacteria. Phytochemical compounds allicin, oleanolic acid, epigallocatechin gallate and curcumin and Jatropha curcas extracts were exceptional synergistic potentiators of various standard antibiotics. CONCLUSION: Considering these facts, phytochemicals represents a valuable and novel source of bioactive compounds with potent antibiotic synergism to modulate bacterial drug-resistance.


Subject(s)
Anthrax/drug therapy , Anti-Bacterial Agents/pharmacology , Bacillus anthracis/chemistry , Drug Synergism , Phytochemicals/isolation & purification , Plant Extracts/pharmacology , Biological Factors , Drug Resistance, Microbial/drug effects , Humans , Microbial Sensitivity Tests , Phytochemicals/pharmacology
8.
Cochrane Database Syst Rev ; 2: CD013099, 2021 02 26.
Article in English | MEDLINE | ID: mdl-33634465

ABSTRACT

BACKGROUND: Bacterial folliculitis and boils are globally prevalent bacterial infections involving inflammation of the hair follicle and the perifollicular tissue. Some folliculitis may resolve spontaneously, but others may progress to boils without treatment. Boils, also known as furuncles, involve adjacent tissue and may progress to cellulitis or lymphadenitis. A systematic review of the best evidence on the available treatments was needed. OBJECTIVES: To assess the effects of interventions (such as topical antibiotics, topical antiseptic agents, systemic antibiotics, phototherapy, and incision and drainage) for people with bacterial folliculitis and boils. SEARCH METHODS: We searched the following databases up to June 2020: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five trials registers up to June 2020. We checked the reference lists of included studies and relevant reviews for further relevant trials.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed systemic antibiotics; topical antibiotics; topical antiseptics, such as topical benzoyl peroxide; phototherapy; and surgical interventions in participants with bacterial folliculitis or boils. Eligible comparators were active intervention, placebo, or no treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'clinical cure' and 'severe adverse events leading to withdrawal of treatment'; secondary outcomes were 'quality of life', 'recurrence of folliculitis or boil following completion of treatment', and 'minor adverse events not leading to withdrawal of treatment'. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 18 RCTs (1300 participants). The studies included more males (332) than females (221), although not all studies reported these data. Seventeen trials were conducted in hospitals, and one was conducted in clinics. The participants included both children and adults (0 to 99 years). The studies did not describe severity in detail; of the 232 participants with folliculitis, 36% were chronic. At least 61% of participants had furuncles or boils, of which at least 47% were incised. Duration of oral and topical treatments ranged from 3 days to 6 weeks, with duration of follow-up ranging from 3 days to 6 months. The study sites included Asia, Europe, and America. Only three trials reported funding, with two funded by industry. Ten studies were at high risk of 'performance bias', five at high risk of 'reporting bias', and three at high risk of 'detection bias'. We did not identify any RCTs comparing topical antibiotics against topical antiseptics, topical antibiotics against systemic antibiotics, or phototherapy against sham light. Eleven trials compared different oral antibiotics. We are uncertain as to whether cefadroxil compared to flucloxacillin (17/21 versus 18/20, risk ratio (RR) 0.90, 95% confidence interval (CI) 0.70 to 1.16; 41 participants; 1 study; 10 days of treatment) or azithromycin compared to cefaclor (8/15 versus 10/16, RR 1.01, 95% CI 0.72 to 1.40; 31 participants; 2 studies; 7 days of treatment) differed in clinical cure (both very low-certainty evidence). There may be little to no difference in clinical cure rate between cefdinir and cefalexin after 17 to 24 days (25/32 versus 32/42, RR 1.00, 95% CI 0.73 to 1.38; 74 participants; 1 study; low-certainty evidence), and there probably is little to no difference in clinical cure rate between cefditoren pivoxil and cefaclor after 7 days (24/46 versus 21/47, RR 1.17, 95% CI 0.77 to 1.78; 93 participants; 1 study; moderate-certainty evidence). For risk of severe adverse events leading to treatment withdrawal, there may be little to no difference between cefdinir versus cefalexin after 17 to 24 days (1/191 versus 1/200, RR 1.05, 95% CI 0.07 to 16.62; 391 participants; 1 study; low-certainty evidence). There may be an increased risk with cefadroxil compared with flucloxacillin after 10 days (6/327 versus 2/324, RR 2.97, 95% CI 0.60 to 14.62; 651 participants; 1 study; low-certainty evidence) and cefditoren pivoxil compared with cefaclor after 7 days (2/77 versus 0/73, RR 4.74, 95% CI 0.23 to 97.17; 150 participants; 1 study; low-certainty evidence). However, for these three comparisons the 95% CI is very wide and includes the possibility of both increased and reduced risk of events. We are uncertain whether azithromycin affects the risk of severe adverse events leading to withdrawal of treatment compared to cefaclor (274 participants; 2 studies; very low-certainty evidence) as no events occurred in either group after seven days. For risk of minor adverse events, there is probably little to no difference between the following comparisons: cefadroxil versus flucloxacillin after 10 days (91/327 versus 116/324, RR 0.78, 95% CI 0.62 to 0.98; 651 participants; 1 study; moderate-certainty evidence) or cefditoren pivoxil versus cefaclor after 7 days (8/77 versus 5/73, RR 1.52, 95% CI 0.52 to 4.42; 150 participants; 1 study; moderate-certainty evidence). We are uncertain of the effect of azithromycin versus cefaclor after seven days due to very low-certainty evidence (7/148 versus 4/126, RR 1.26, 95% CI 0.38 to 4.17; 274 participants; 2 studies). The study comparing cefdinir versus cefalexin did not report data for total minor adverse events, but both groups experienced diarrhoea, nausea, and vaginal mycosis during 17 to 24 days of treatment. Additional adverse events reported in the other included studies were vomiting, rashes, and gastrointestinal symptoms such as stomach ache, with some events leading to study withdrawal. Three included studies assessed recurrence following completion of treatment, none of which evaluated our key comparisons, and no studies assessed quality of life. AUTHORS' CONCLUSIONS: We found no RCTs regarding the efficacy and safety of topical antibiotics versus antiseptics, topical versus systemic antibiotics, or phototherapy versus sham light for treating bacterial folliculitis or boils. Comparative trials have not identified important differences in efficacy or safety outcomes between different oral antibiotics for treating bacterial folliculitis or boils. Most of the included studies assessed participants with skin and soft tissue infection which included many disease types, whilst others focused specifically on folliculitis or boils. Antibiotic sensitivity data for causative organisms were often not reported. Future trials should incorporate culture and sensitivity information and consider comparing topical antibiotic with antiseptic, and topical versus systemic antibiotics or phototherapy.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Furunculosis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Infective Agents, Local/therapeutic use , Bias , Carbuncle/drug therapy , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Randomized Controlled Trials as Topic , Young Adult
9.
Toxins (Basel) ; 13(1)2021 01 13.
Article in English | MEDLINE | ID: mdl-33450877

ABSTRACT

Anti-toxin agents for severe B. anthracis infection will only be effective if they add to the benefit of the two mainstays of septic shock management, antibiotic therapy and titrated hemodynamic support. Both of these standard therapies could negate benefits related to anti-toxin treatment. At present, three anthrax anti-toxin antibody preparations have received US Food and Drug Administration (FDA) approval: Raxibacumab, Anthrax Immune Globulin Intravenous (AIGIV) and ETI-204. Each agent is directed at the protective antigen component of lethal and edema toxin. All three agents were compared to placebo in antibiotic-treated animal models of live B. anthracis infection, and Raxibacumab and AIGIV were compared to placebo when combined with standard hemodynamic support in a 96 h canine model of anthrax toxin-associated shock. However, only AIG has actually been administered to a group of infected patients, and this experience was not controlled and offers little insight into the efficacy of the agents. To provide a broader view of the potential effectiveness of these agents, this review examines the controlled preclinical experience either in antibiotic-treated B. anthracis models or in titrated hemodynamic-supported toxin-challenged canines. The strength and weaknesses of these preclinical experiences are discussed.


Subject(s)
Anthrax/drug therapy , Anti-Bacterial Agents/therapeutic use , Antigens, Bacterial , Antitoxins/therapeutic use , Bacterial Toxins , Shock, Septic/therapy , Animals , Antibodies, Monoclonal/therapeutic use , Bacillus anthracis/drug effects , Disease Models, Animal , Dogs , Drug Evaluation, Preclinical , Drug Therapy, Combination , Hemodynamics , Humans , Immunoglobulins, Intravenous , United States , United States Food and Drug Administration
10.
J Infect Dis ; 223(2): 319-325, 2021 02 03.
Article in English | MEDLINE | ID: mdl-32697310

ABSTRACT

BACKGROUND: Inhalational anthrax is rare and clinical experience limited. Expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking. METHODS: Rhesus macaques exposed to an aerosol of Bacillus anthracis spores were treated with ciprofloxacin, clindamycin, or ciprofloxacin + clindamycin after becoming bacteremic. Circulating anthrax lethal factor and protective antigen were quantitated pretreatment and 1.5 and 12 hours after beginning antibiotics. RESULTS: In the clindamycin group, 8 of 11 (73%) survived demonstrating its efficacy for the first time in inhalational anthrax, compared to 9 of 9 (100%) with ciprofloxacin, and 8 of 11 (73%) with ciprofloxacin + clindamycin. These differences were not statistically significant. There were no significant differences between groups in lethal factor or protective antigen levels from pretreatment to 12 hours after starting antibiotics. Animals that died after clindamycin had a greater incidence of meningitis compared to those given ciprofloxacin or ciprofloxacin + clindamycin, but numbers of animals were very low and no definitive conclusion could be reached. CONCLUSION: Treatment of inhalational anthrax with clindamycin was as effective as ciprofloxacin in the nonhuman primate. Addition of clindamycin to ciprofloxacin did not enhance reduction of circulating toxin levels.


Subject(s)
Anthrax/blood , Anthrax/prevention & control , Antigens, Bacterial/blood , Bacillus anthracis/drug effects , Bacillus anthracis/physiology , Bacterial Toxins/blood , Ciprofloxacin/therapeutic use , Clindamycin/therapeutic use , Respiratory Tract Infections/blood , Respiratory Tract Infections/prevention & control , Animals , Anthrax/microbiology , Anthrax/mortality , Anti-Bacterial Agents/therapeutic use , Biomarkers , Ciprofloxacin/pharmacology , Clindamycin/pharmacology , Disease Models, Animal , Drug Therapy, Combination , Macaca mulatta , Prognosis , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , Treatment Outcome
11.
Infect Immun ; 88(8)2020 07 21.
Article in English | MEDLINE | ID: mdl-32393506

ABSTRACT

Bacillus anthracis is the causative agent of anthrax disease, presents with high mortality, and has been at the center of bioweapon efforts. The only currently U.S. FDA-approved vaccine to prevent anthrax in humans is anthrax vaccine adsorbed (AVA), which is protective in several animal models and induces neutralizing antibodies against protective antigen (PA), the cell-binding component of anthrax toxin. However, AVA requires a five-course regimen to induce immunity, along with an annual booster, and is composed of undefined culture supernatants from a PA-secreting strain. In addition, it appears to be ineffective against strains that lack anthrax toxin. Here, we investigated a vaccine formulation consisting of recombinant proteins from a surface-localized heme transport system containing near-iron transporter (NEAT) domains and its efficacy as a vaccine for anthrax disease. The cocktail of five NEAT domains was protective against a lethal challenge of inhaled bacillus spores at 3 and 28 weeks after vaccination. The reduction of the formulation to three NEATs (IsdX1, IsdX2, and Bslk) was as effective as a five-NEAT domain cocktail. The adjuvant alum, approved for use in humans, was as protective as Freund's Adjuvant, and protective vaccination correlated with increased anti-NEAT antibody reactivity and reduced bacterial levels in organs. Finally, the passive transfer of anti-NEAT antisera reduced mortality and disease severity, suggesting the protective component is comprised of antibodies. Collectively, these results provide evidence that a vaccine based upon recombinant NEAT proteins should be considered in the development of a next-generation anthrax vaccine.


Subject(s)
Anthrax Vaccines/immunology , Anthrax/prevention & control , Antibodies, Bacterial/biosynthesis , Antibodies, Neutralizing/biosynthesis , Antigens, Bacterial/immunology , Bacillus anthracis/drug effects , Administration, Inhalation , Alum Compounds/administration & dosage , Animals , Anthrax/immunology , Anthrax/microbiology , Anthrax/mortality , Anthrax Vaccines/administration & dosage , Anthrax Vaccines/genetics , Antigens, Bacterial/administration & dosage , Antigens, Bacterial/genetics , Bacillus anthracis/immunology , Bacillus anthracis/pathogenicity , Bacterial Proteins/administration & dosage , Bacterial Proteins/genetics , Bacterial Proteins/immunology , Carrier Proteins/administration & dosage , Carrier Proteins/genetics , Carrier Proteins/immunology , Complement C5/deficiency , Female , Freund's Adjuvant/administration & dosage , Humans , Immunogenicity, Vaccine , Mice, Knockout , Survival Analysis , Vaccination/methods
12.
PLoS One ; 15(1): e0228162, 2020.
Article in English | MEDLINE | ID: mdl-31978152

ABSTRACT

The in vivo efficacy of liposomal encapsulated ciprofloxacin in two formulations, lipoquin and apulmiq, were evaluated against the causative agent of anthrax, Bacillus anthracis. Liposomal encapsulated ciprofloxacin is attractive as a therapy since it allows for once daily dosing and achieves higher concentrations of the antibiotic at the site of initial mucosal entry but lower systemic drug concentrations. The in vivo efficacy of lipoquin and apulmiq delivered by intranasal instillation was studied at different doses and schedules in both a post exposure prophylaxis (PEP) therapy model and in a delayed treatment model of murine inhalational anthrax. In the mouse model of infection, the survival curves for all treatment cohorts differed significantly from the vehicle control. Ciprofloxacin, lipoquin and apulmiq provided a high level of protection (87-90%) after 7 days of therapy when administered within 24 hours of exposure. Reducing therapy to only three days still provided protection of 60-87%, if therapy was provided within 24 hours of exposure. If treatment was initiated 48 hours after exposure the survival rate was reduced to 46-65%. These studies suggest that lipoquin and apulmiq may be attractive therapies as PEP and as part of a treatment cocktail for B. anthracis.


Subject(s)
Anthrax/drug therapy , Ciprofloxacin/therapeutic use , Liposomes/chemistry , Administration, Intranasal , Animals , Anthrax/microbiology , Anthrax/mortality , Bacillus anthracis/pathogenicity , Ciprofloxacin/chemistry , Disease Models, Animal , Drug Compounding , Female , Mice , Mice, Inbred BALB C , Survival Rate
13.
Med Microbiol Immunol ; 209(2): 125-137, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31811379

ABSTRACT

The most promising means of controlling anthrax, a lethal zoonotic disease during the early infection stages, entail restricting the resilient infectious form, i.e., the spores from proliferating to replicating bacilli in the host. The extractible antigen (EA1), a major S-layer protein present on the vegetative cells and spores of Bacillus anthracis, is highly immunogenic and protects mice against lethal challenge upon immunization. In the present study, mice were immunized with r-EA1C, the C terminal crystallization domain of EA1, to generate a neutralizing monoclonal antibody EA752-862, that was evaluated for its anti-spore and anti-bacterial properties. The monoclonal antibody EA752-862 had a minimum inhibitory concentration of 0.08 mg/ml, was bactericidal at a concentration of 0.1 mg/ml and resulted in 100% survival of mice against challenge with B. anthracis vegetative cells. Bacterial cell lysis as observed by scanning electron microscopy and nucleic acid leakage assay could be attributed as a possible mechanism for the bactericidal property. The association of mAb EA752-862 with spores inhibits their subsequent germination to vegetative cells in vitro, enhances phagocytosis of the spores and killing of the vegetative cells within the macrophage, and subsequently resulted in 90% survival of mice upon B. anthracis Ames spore challenge. Therefore, owing to its anti-spore and bactericidal properties, the present study demonstrates mAb EA752-862 as an efficient neutralizing antibody that hinders the establishment of early infection before massive multiplication and toxin release takes place.


Subject(s)
Anthrax/prevention & control , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Bacillus anthracis/immunology , Spores, Bacterial/immunology , Animals , Anthrax/immunology , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antibodies, Bacterial/biosynthesis , Antibodies, Bacterial/chemistry , Antibodies, Bacterial/isolation & purification , Antibodies, Bacterial/pharmacology , Antibodies, Monoclonal/biosynthesis , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/pharmacology , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/isolation & purification , Antibodies, Neutralizing/pharmacology , Antigens, Bacterial/immunology , Bacillus anthracis/drug effects , Binding Sites , Female , Immunization , Macrophages/drug effects , Macrophages/immunology , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Phagocytosis/drug effects , Phagocytosis/immunology , Spores, Bacterial/drug effects
14.
Hum Vaccin Immunother ; 16(7): 1699-1707, 2020 07 02.
Article in English | MEDLINE | ID: mdl-31809637

ABSTRACT

Polysaccharides isolated from natural plants may represent a novel source of vaccine adjuvants. In this research, we focused on a natural plant polysaccharide, PCP-I, which is derived from Poria cocos, a Chinese traditional herbal medicine. We chose the anthrax protective antigen (PA) as a model to evaluate the adjuvant ability of PCP-I in enhancing the immunogenicity and protection of a PA-based anthrax vaccine. According to our results, PCP-I could significantly enhance anthrax specific anti-PA antibodies, toxin-neutralizing antibodies, anti-PA antibody affinity, as well as IgG1 and IgG2a levels. Besides, PCP-I increased the frequency of PA-specific memory B cells, increased the proliferation of PA-specific splenocytes, significantly stimulated the secretion of IL-4, and enhanced the activation of Dendritic cells (DCs) in vitro. The combination of PCP-I and CpG significantly enhanced the level of anti-PA antibodies and neutralizing antibodies, particularly PA-specific IgG2a, and shifted the Th2-bias to a Th1/Th2 balanced response. In addition, PCP-I with or without CpG could significantly improve the survival rate of immunized mice following challenge with the anthrax lethal toxin. These findings suggest that PCP-I may be a promising vaccine adjuvant that warrants further study.


Subject(s)
Anthrax Vaccines , Anthrax , Bacillus anthracis , Wolfiporia , Animals , Anthrax/prevention & control , Antibodies, Bacterial , Antigens, Bacterial , Bacterial Toxins , Mice , Mice, Inbred BALB C , Polysaccharides
15.
BMC Public Health ; 19(1): 1625, 2019 Dec 03.
Article in English | MEDLINE | ID: mdl-31796011

ABSTRACT

BACKGROUND: Knowledge, attitudes, and practices (KAP) surveys regarding zoonotic diseases are crucial to understanding the extent of knowledge among citizens and for guiding health-related education programs. METHOD: Employing a structured questionnaire, we interviewed residents (n = 388) in three districts of northern Tanzania (Karatu n = 128, Monduli n = 114, Babati n = 146) to assess knowledge, attitudes and reported practices regarding three zoonotic diseases that occur in the region (anthrax, brucellosis, and rabies). We used generalized linear mixed effects models and multi-model inference to identify demographic correlates of knowledge. RESULTS: Proportional average district- and disease- specific knowledge scores ranged from 0.14-0.61. We found positive correlations between age and knowledge of symptoms, causes and treatments of anthrax (three districts), brucellosis (three districts), and rabies (one district). Gender, ethnic identity, formal education and ownership of livestock or dogs had variable effects on knowledge among the interviewed population. Risk perceptions regarding different diseases varied across districts and were positively correlated with knowledge of the specific diseases. Direct interactions with livestock and domestic dogs were reported to occur across all demographic groups, suggesting that most people living in rural settings of our study area are potentially exposed to zoonotic diseases. Behaviors which may favor transmission of specific pathogens (such as consumption of raw milk or meat) were occasionally reported and varied by district. Wildlife was generally regarded as negative or neutral with regard to overall veterinary and human health. CONCLUSION: The combination of variable knowledge about zoonotic diseases in the three districts, reported occurrence of practices that are conducive to pathogen transmission, and previously documented circulation of pathogens causing anthrax, brucellosis and rabies in our study system, call for health education programs embedded in a holistic One Health approach.


Subject(s)
Anthrax/psychology , Brucellosis/psychology , Health Knowledge, Attitudes, Practice , Rabies/psychology , Zoonoses/psychology , Adult , Animals , Female , Health Behavior , Health Education , Humans , Linear Models , Male , Middle Aged , Rural Population , Surveys and Questionnaires , Tanzania/epidemiology
16.
mSphere ; 4(3)2019 06 19.
Article in English | MEDLINE | ID: mdl-31217301

ABSTRACT

Inhalational anthrax caused by Bacillus anthracis, a spore-forming Gram-positive bacterium, is a highly lethal infection. Antibodies targeting the protective antigen (PA) binding component of the toxins have recently been authorized as an adjunct to antibiotics, although no conclusive evidence demonstrates that anthrax antitoxin therapy has any significant benefit. We discuss here the rational basis of anti-PA development regarding the pathogenesis of the disease. We argue that inductive reasoning may induce therapeutic bias. We identified anthrax animal model analysis as another bias. Further studies are needed to assess the benefit of anti-PA antibodies in the treatment of inhalational anthrax, while a clearer consensus should be established around what evidence should be proven in an anthrax model.


Subject(s)
Anthrax/immunology , Anthrax/therapy , Antibodies, Bacterial/therapeutic use , Bacillus anthracis/immunology , Immunotherapy , Respiratory Tract Infections/immunology , Respiratory Tract Infections/therapy , Animals , Antibodies, Monoclonal/therapeutic use , Antigens, Bacterial/immunology , Antitoxins/therapeutic use , Bacterial Toxins/immunology , Disease Models, Animal , Drug Evaluation, Preclinical , Humans
17.
J Infect Dev Ctries ; 13(2): 118-122, 2019 02 28.
Article in English | MEDLINE | ID: mdl-32036346

ABSTRACT

INTRODUCTION: Cutaneous anthrax (CA), a zoonotic infectious disease is an important endemic public health disease in rural areas around the world, accounting for 95% of anthrax cases. METHODOLOGY: Fifty patients with CA were diagnosed by the presence of characteristic skin lesions and positive response to treatment. Twenty-nine patients had been treated with oral ciprofloxacin or doxycyclin for 14 days and 21 patients had been treated with intramuscular procaine penicillin for 7 days. The demographic risk factors, characteristics and treatment of CA in rural areas were evaluated. The responses to two different systemic medications were compared using χ2 test. RESULTS: Twenty-two males and 28 females were included in this study. The predominant skin lesions were black eschar, ulcer and swelling of the skin. The predilection sites were the hand and fingers. The most common route of contamination for both male and female patients was handling raw meat. The most common occupation was housewife for female patients and animal industry for male patients. The patients under ciprofloxacin or doxycyclin administration responded better to treatment; pain at lesion site and new lesions at the time of treatment were significantly lower. Secondary infection appeared to be higher in patients under procaine penicillin administration, although this difference was not statistically significant. CONCLUSIONS: In rural areas that lack medical facilities with diagnostic tools, in the presence of black eschar, rapid diagnosis and treatment of CA is essential. The administration of a broad-spectrum antibiotic is recommended as the first line treatment of suspected CA.


Subject(s)
Anthrax/drug therapy , Anthrax/epidemiology , Ciprofloxacin/therapeutic use , Doxycycline/therapeutic use , Rural Population , Skin Diseases, Bacterial/drug therapy , Skin Diseases, Bacterial/epidemiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Female , Humans , Male , Meat/microbiology , Middle Aged , Young Adult
19.
mBio ; 9(5)2018 10 16.
Article in English | MEDLINE | ID: mdl-30327445

ABSTRACT

Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, are two of the deadliest pathogenic bacteria that have been used as biological warfare agents. Although Biothrax is a licensed vaccine against anthrax, no Food and Drug Administration-approved vaccine exists for plague. Here, we report the development of a dual anthrax-plague nanoparticle vaccine employing bacteriophage (phage) T4 as a platform. Using an in vitro assembly system, the 120- by 86-nm heads (capsids) of phage T4 were arrayed with anthrax and plague antigens fused to the small outer capsid protein Soc (9 kDa). The antigens included the anthrax protective antigen (PA) (83 kDa) and the mutated (mut) capsular antigen F1 and the low-calcium-response V antigen of the type 3 secretion system from Y. pestis (F1mutV) (56 kDa). These viral nanoparticles elicited robust anthrax- and plague-specific immune responses and provided complete protection against inhalational anthrax and/or pneumonic plague in three animal challenge models, namely, mice, rats, and rabbits. Protection was demonstrated even when the animals were simultaneously challenged with lethal doses of both anthrax lethal toxin and Y. pestis CO92 bacteria. Unlike the traditional subunit vaccines, the phage T4 vaccine uses a highly stable nanoparticle scaffold, provides multivalency, requires no adjuvant, and elicits broad T-helper 1 and 2 immune responses that are essential for complete clearance of bacteria during infection. Therefore, phage T4 is a unique nanoparticle platform to formulate multivalent vaccines against high-risk pathogens for national preparedness against potential bioterror attacks and emerging infections.IMPORTANCE Following the deadly anthrax attacks of 2001, the Centers for Disease Control and Prevention (CDC) determined that Bacillus anthracis and Yersinia pestis that cause anthrax and plague, respectively, are two Tier 1 select agents that pose the greatest threat to the national security of the United States. Both cause rapid death, in 3 to 6 days, of exposed individuals. We engineered a virus nanoparticle vaccine using bacteriophage T4 by incorporating key antigens of both B. anthracis and Y. pestis into one formulation. Two doses of this vaccine provided complete protection against both inhalational anthrax and pneumonic plague in animal models. This dual anthrax-plague vaccine is a strong candidate for stockpiling against a potential bioterror attack involving either one or both of these biothreat agents. Further, our results establish the T4 nanoparticle as a novel platform to develop multivalent vaccines against pathogens of high public health significance.


Subject(s)
Anthrax Vaccines/immunology , Anthrax/prevention & control , Antigens, Bacterial/immunology , Bacteriophage T4 , Plague Vaccine/immunology , Plague/prevention & control , Respiratory Tract Infections/prevention & control , Animals , Antibodies, Bacterial/blood , Bacillus anthracis , Bacterial Proteins/immunology , Bacterial Toxins/immunology , Capsid Proteins/immunology , Female , Male , Mice , Mice, Inbred BALB C , Nanoparticles , Pore Forming Cytotoxic Proteins/immunology , Rabbits , Rats , Th1 Cells/immunology , Th2 Cells/immunology , Yersinia pestis
20.
Article in English | MEDLINE | ID: mdl-29661872

ABSTRACT

Treatment of anthrax is challenging, especially during the advanced stages of the disease. Recently, the Centers for Disease Control and Prevention (CDC) updated its recommendations for postexposure prophylaxis and treatment of exposed populations (before and after symptom onset). These recommendations distinguished, for the first time, between systemic disease with and without meningitis, a common and serious complication of anthrax. The CDC considers all systemic cases meningeal unless positively proven otherwise. The treatment of patients suffering from systemic anthrax with suspected or confirmed meningitis includes the combination of three antibiotics, i.e., a fluoroquinolone (levofloxacin or ciprofloxacin), a ß-lactam (meropenem or imipenem), and a protein synthesis inhibitor (linezolid or clindamycin). In addition, treatment with an antitoxin (anti-protective antigen antibodies) and dexamethasone should be applied. Since the efficacy of most of these treatments has not been demonstrated, especially in animal meningitis models, we developed an anthrax meningitis model in rabbits and tested several of these recommendations. We demonstrated that, in this model, ciprofloxacin, linezolid, and meropenem were ineffective as single treatments, while clindamycin was highly effective. Furthermore, combined treatments of ciprofloxacin and linezolid or ciprofloxacin and dexamethasone failed in treating rabbits with meningitis. We demonstrated that dexamethasone actually hindered blood-brain barrier penetration by antibiotics, reducing the effectiveness of antibiotic treatment of anthrax meningitis in this rabbit model.


Subject(s)
Anthrax/drug therapy , Anti-Bacterial Agents/therapeutic use , Antitoxins/therapeutic use , Bacillus anthracis/drug effects , Meningitis, Bacterial/drug therapy , Animals , Anthrax/pathology , Central Nervous System/microbiology , Central Nervous System/pathology , Ciprofloxacin/therapeutic use , Clindamycin/therapeutic use , Dexamethasone/therapeutic use , Disease Models, Animal , Drug Combinations , Imipenem/therapeutic use , Levofloxacin/therapeutic use , Linezolid/therapeutic use , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/pathology , Meropenem/therapeutic use , Rabbits , Treatment Failure
SELECTION OF CITATIONS
SEARCH DETAIL