The global patent landscape of emerging infectious disease monkeypox.

BACKGROUND: Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. METHODS: A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. RESULTS: Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. CONCLUSIONS: Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.

Ethnobotanical Uses, Phytochemistry, Toxicology, and Pharmacological Properties of Euphorbia neriifolia Linn. against Infectious Diseases: A Comprehensive Review.

Medicinal plants have considerable potential as antimicrobial agents due to the presence of secondary metabolites. This comprehensive overview aims to summarize the classification, morphology, and ethnobotanical uses of Euphorbia neriifolia L. and its derived phytochemicals with the recent updates on the pharmacological properties against emerging infectious diseases, mainly focusing on bacterial, viral, fungal, and parasitic infections. The data were collected from electronic databases, including Google Scholar, PubMed, Semantic Scholar, ScienceDirect, and SpringerLink by utilizing several keywords like 'Euphorbia neriifolia', 'phytoconstituents', 'traditional uses', 'ethnopharmacological uses', 'infectious diseases', 'molecular mechanisms', 'COVID-19', 'bacterial infection', 'viral infection', etc. The results related to the antimicrobial actions of these plant extracts and their derived phytochemicals were carefully reviewed and summarized. Euphol, monohydroxy triterpene, nerifoliol, taraxerol, ß-amyrin, glut-5-(10)-en-1-one, neriifolione, and cycloartenol are the leading secondary metabolites reported in phytochemical investigations. These chemicals have been shown to possess a wide spectrum of biological functions. Different extracts of E. neriifolia exerted antimicrobial activities against various pathogens to different extents. Moreover, major phytoconstituents present in this plant, such as quercetin, rutin, friedelin, taraxerol, epitaraxerol, taraxeryl acetate, 3ß-friedelanol, 3ß-acetoxy friedelane, 3ß-simiarenol, afzelin, 24-methylene cycloarenol, ingenol triacetate, and ß-amyrin, showed significant antimicrobial activities against various pathogens that are responsible for emerging infectious diseases. This plant and the phytoconstituents, such as flavonoids, monoterpenoids, diterpenoids, triterpenoids, and alkaloids, have been found to have significant antimicrobial properties. The current evidence suggests that they might be used as leads in the development of more effective drugs to treat emerging infectious diseases, including the 2019 coronavirus disease (COVID-19).

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope® registry and from the literature.

BACKGROUND: The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi. OBJECTIVES: To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection. PATIENTS/METHODS: Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope® registry and all reported cases from a literature were included. RESULTS: We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft-versus-host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9). CONCLUSION: Rasamsonia spp. are emerging fungi causing life-threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency.

Candidemia due to uncommon Candida species in children: new threat and impacts on outcomes.

Many uncommon Candida spp. (species other than C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. krusei) have been shown to emerge in tertiary care facilities. We aimed to investigate these uncommon candidemia in children. Forty-six cases of candidemia caused by uncommon Candida spp. were identified during 2003-2015 from a medical center in Taiwan. The most common specie was C. guilliermondii (31.2%), followed by C. lusitaniae (18.8%) and C. metapsilosis (18.8%). These cases were analyzed and compared with 148 episodes of C. albicans candidemia. The incidence density of uncommon Candida spp. candidemia and the proportion to all candidemia episodes increased substantively during the study period. Prior exposure to azoles was uncommon in the 30 days prior to infection, but fluconazole resistant strains were significantly more common (n = 19, 41.3%). The increased incidence density of uncommon Candida spp. candidemia was associated with increasing use of antifungal agents. No differences in demographics, underlying comorbidities, risk factors, clinical features, dissemination, and 30-day mortality were found between uncommon Candida spp. and C. albicans candidemia. Patients with uncommon Candida spp. candidemia were more likely to require modifications in antifungal treatment and receive echinocandin drugs (43.5% vs 21.6%, p = 0.007). Candidemia caused by uncommon Candida spp. had poorer response to antifungal treatment, led to longer duration of candidemia (median 4.0 versus 2.5 days, p = 0.008), and had a higher treatment failure rate (56.5% vs 38.5%, p = 0.040).

Collateral damage of using colistin in hospitalized patients on emergence of colistin-resistant Escherichia coli and Klebsiella pneumoniae colonization and infection.

Background: Colistin has been used for therapy of carbapenem-resistant Gram-negative infections in Thailand, especially carbapenem-resistant A. baumannii and P. aeruginosa, for more than 10 years. However, the prevalence of colistin-resistant A. baumannii or P. aeruginosa is still less than 5%. Colistin-resistant Enterobacteriaceae has been increasingly reported globally over the past few years and the use of colistin in food animals might be associated with an emergence of colistin resistance in Enterobacteriaceae. This study aimed to determine the effect of colistin exposure in hospitalized patients who received colistin on development of colistin-resistant (CoR) Escherichia coli (EC) or Klebsiella pneumoniae (KP) colonization and infection. Methods: A prospective observational study was performed in adult hospitalized patients at Siriraj Hospital who received colistin for treatment of infections during December 2016 and November 2017. The surveillance culture samples were collected from the stool and the site of infection of each patient who received colistin at the study enrollment, days 3 and 7 after the study enrollment, and once a week thereafter for determination of CoR EC and CoR KP. CoR EC and CoR KP were also tested for a presence of mcr-1 gene. Results: One hundred thirty-nine patients were included. Overall prevalence of CoR EC or CoR KP colonization was 47.5% among 139 subjects. Prevalence of CoR EC or CoR KP colonization was 17.3% of subjects at study enrollment, and 30.2% after study enrollment. Use of fluoroquinolones, aminoglycosides, and colistin was found to be significantly associated with CoR EC or CoR KP colonization. The mcr-1 gene was detected in 13.0% of CoR EC or CoR KP isolates, and in 27.3% of subjects with CoR EC or CoR KP colonization. CoR EC or CoR KP colonization persisted in 65.2% of the subjects at the end of the study. Five patients with CoR KP infections received combination antibiotics and they were alive at hospital discharge. Conclusions: Prevalence of CoR EC or CoR KP colonization in hospitalized patients receiving colistin was high and it was associated with the use of colistin. Therefore, patients who receive colistin are at risk of developing CoR EC or CoR KP colonization and infection.

Acceptance of the 2016 Eminent Parasitologist Award: Chemotherapy in the Context of Emerging Parasitic Diseases.

It seems inevitable that chemotherapy will continue, at least in the near-term, to be a significant factor in the control of infectious diseases. The effectiveness of new drugs has invariably been reduced by the emergence of drug resistance. Efforts to thwart resistance should continue, but there are also other areas that might profitably be re-examined. They include (1) methods of new-drug discovery; (2) selection of parasite life-cycle targets; (3) epidemiological determinants of effectiveness in large-scale control programs; and (4) the economic, managerial, psychological, and political ramifications of drug discovery and drug utilization.

In vitro activity of gentamicin and amikacin against Salmonella enterica serovar Typhi: a search for a treatment regimen for typhoid fever.

The emergence of Salmonella enterica serovar Typhi isolates resistant to ciprofloxacin and 3rd-generation cephalosporins is a concern for physicians in developing countries. This study assessed the in vitro activity of gentamicin and amikacin against 464 S. entenca serovar Typhi isolates obtained from blood of patients clinically suspected of enteric fever who attended the Calcutta School of Tropical Medicine from 1991 to 2003. The isolates were sensitive to gentamicin and amikacin, showing minimum inhibitory concentrations 0.01-4 microg/mL and 0.005-3.5 microg/mL respectively. Both agents showed bactericidal activity at concentrations of 2 microg/mL after incubation for 6 hours. Aminoglycoside antibiotics such as gentamicin and amikacin may thus be introduced as a treatment regimen for typhoid fever.

[Emergence pathogens infections in ENT Department of Children's hospital in 2005-2008]. / Zakazenia patogenami alarmowymi na Oddziale Otolaryngologicznym Szpitala Dzieciecego im. prof. dr. med. Jana Bogdanowicza w latach 2005-2008.

INTRODUCTION: The development of medicine, in this the new techniques and antibiotic therapy enlarged the survivability of patients in hospital. Applying antibiotics caused breakthrough in treatment stepping out in ill's group infections treated in hospital, however enlarging resistance is natural this effect, resulting from: the selection of resistant strains, the formation of new mechanisms of resistance, and/or the spreading of gene of resistance. Multidrug-resistant strains were included to emergence-pathogens group: MRSA, penicillin-resistant Streptococcus pneumoniae, VRE, Gram-negative producing beta-lactamase of type the ESBL and/or resistant to carbapenems. Emergence-pathogens occurrence leads to: therapeutic failures, the use extorts in therapy of dear medicines or with possibility of workings undesirable. The multidrug-resistant strains spread in hospital environment easily, especially on departments about high waste of medicines with the patients' simultaneously large susceptibility on infection, resulting mainly with state of reduced resistance of organism. The control of hospital infections recognize by present hospitality for the most important criterion of quality of work. AIM: Analysis of the emergence-pathogens isolated during treatment in hospital in 2005-2008, from special regard the ENT Department. MATERIAL AND METHODS: 50586 children treated in this period in hospital in which was executed 39386 bacteriological investigations, in this 6528 (12.9%) children in ENT Department in which was executed 1566 bacteriological investigations (3.98%). The diagnostics were executed according to routine microbiological procedures with qualification of resistance to antibiotics. RESULTS: Emergence-pathogens infection was confirmed at 2369 children's (4.68%) treated in Hospital, in this in ENT Department at 84 children (1.29%). The most frequent emergence-pathogens in ENT Department were Streptococcus pyogenes, Streptococcus pneumoniae penicillin-resistant and average sensitive on penicillin, Staphylococcus aureus methicillin-resistant and Rotavirus. CONCLUSIONS: Streptococcus pneumoniae penicillin-resistant and average sensitive to penicillin and Rotavirus infections are the most frequent hospital infections. The systematic microbiological supervision is indispensable in prevention the spreading of infections of the emergence-pathogens in hospital.

Unique small molecule entry inhibitors of hemorrhagic fever arenaviruses.

Viral hemorrhagic fevers caused by the arenaviruses Lassa virus in Africa and Machupo, Guanarito, Junin, and Sabia virus in South America are among the most devastating emerging human diseases with fatality rates of 15-35% and a limited antiviral therapeutic repertoire available. Here we used high throughput screening of synthetic combinatorial small molecule libraries to identify inhibitors of arenavirus infection using pseudotyped virion particles bearing the glycoproteins (GPs) of highly pathogenic arenaviruses. Our screening efforts resulted in the discovery of a series of novel small molecule inhibitors of viral entry that are highly active against both Old World and New World hemorrhagic arenaviruses. We observed potent inhibition of infection of human and primate cells with live hemorrhagic arenaviruses (IC(50)=500-800 nm). Investigations of the mechanism of action revealed that the candidate compounds efficiently block pH-dependent fusion by the arenavirus GPs (IC(50) of 200-350 nm). Although our lead compounds were potent against phylogenetically distant arenaviruses, they did not show activity against other enveloped viruses with class I viral fusion proteins, indicating specificity for arenavirus GP-mediated membrane fusion.

"Discovery to treatment" window in patients with smear-positive pulmonary tuberculosis.

Delay in commencing treatment in patients diagnosed with smear-positive pulmonary tuberculosis (PTB) may promote the spread of PTB in the community. Socio-demographic and clinical data from 169 patients (119 retrospectively and 50 prospectively collected) treated for smear-positive PTB in our hospital Chest Clinic from June 2002 to February 2003 were analysed. One hundred and fifty eight (93.5%) patients were started on treatment in less than 7 days from the time when the report first became available while 11 (6.5%) patients had their treatment started > or = 7 days. The median 'discovery to treatment' window was 1 day (range, 0 to 24 days). Of the factors studied, longevity of symptoms, absence of fever or night sweats and having sought traditional medicine were associated with delay in treatment commencement. The urgency and importance of anti-TB treatment should be emphasized especially to patients who are inclined towards treatment with traditional medicine.

Infectious keratitis in South Australia: emerging resistance to cephazolin.

PURPOSE: To analyze the microbiologic spectrum and patterns of resistance of infectious keratitis in patients treated at a tertiary hospital in South Australia. METHODS: Retrospective review of microbiology laboratory records of all patients with infectious keratitis who had corneal scrapings, from 1998 to 2003. All records were subsequently reviewed for Gram staining and culture results, as well as antibiotic sensitivity and resistance. RESULTS: Positive corneal cultures were obtained in 134 out of 211 patients who had corneal scrapings (63.5%). Coagulase negative Staphylococcus was the commonest pathogen identified (29.8% of positive cultures), followed by Staphylococcus aureus (18.7%), Pseudomonas aeruginosa (12.7%), Moraxella (6.7%), Streptococcus pneumonia (6.0%), and fungal keratitis (5.2%). In 43.3% of culture positive cases, the organisms were also identified in Gram stain, and in all these cases there was a full correlation between the two methods. In vitro sensitivities were highest for gentamicin. Fourteen cases (35%) of coagulase negative Staphylococcus were found to be resistant to cephazolin. No ciprofloxacin resistance was identified in all Pseudomonas isolates tested. CONCLUSIONS: Staphylococcus species continue to be the commonest causative organism for infectious keratitis; however, there is an emerging resistance to cephazolin, which is commonly used as the first-line antibiotic for Gram-positive cocci.

Emerging nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from patients having acute diarrhoeal disease.

BACKGROUND: Non-typhoidal Salmonella are one of the key etiological agents of diarrhoeal disease. The appearance of multiple drug resistance along with resistance to quinolones in this bacterium poses a serious therapeutic problem. We determined the prevalence of nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from faecal samples of patients with acute diarrhoeal disease attending the outpatient and inpatient department of a hospital in Saudi Arabia during the years 1999 to 2002. METHODS: Non-typhoidal Salmonella were isolated from faecal samples. Antimicrobial susceptibility was tested by the disc diffusion test. MICs to nalidixic acid and ciprofloxacin were determined by the agar dilution method. RESULTS: During the study period, 524 strains of non-typhoidal Salmonella were isolated. Strains belonging to serogroup C1 were the commonest (41.4%) followed by serogroups B and D (15.6% and 14.5%, respectively). Resistance to ampicillin was observed in 22.9% and to trimethoprim/sulfamethoxazole in 18.5% of the strains. Nalidixic acid resistance was encountered in 9.9% and ciprofloxacin resistance in 2.3% of the strains. Resistance to nalidixic acid significantly increased from 0.1% in 1999 to 5.5% in 2002 (P=0.0007) and ciprofloxacin resistance increased significantly from 0.1% in 1999 to 0.9% in 2002 (P=0.0001). MICs to nalidixic acid and ciprofloxacin were determined among 29 nalidixic acid-resistant strains of non-typhoidal Salmonella isolated during 2002. The MIC was >256 microg/mL to nalidixic acid and 8 to 16 microg/mL to ciprofloxacin. CONCLUSION: The increasing rates of antimicrobial resistance encountered among non-typhoidal Salmonella necessitate the judicious use of these drugs in humans. Moreover, these findings support the concern that the use of quinolones in animal feed may lead to an increase in resistance and should be restricted.

Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B.

Aspergillus terreus is an uncommon but emerging fungal pathogen, which causes lethal infections that are often refractory to amphotericin B (AmB). In comparison to Aspergillus fumigatus, A. terreus was resistant to the in vitro fungicidal effects of safely achievable concentrations of AmB. These in vitro findings correlated directly with resistance of A. terreus to AmB in experimental invasive pulmonary aspergillosis. Residual fungal pulmonary burden and galactomannan antigenemia demonstrated persistent infection, despite therapy with deoxycholate AmB or liposomal AmB. By comparison, posaconazole and itraconazole resolved GM antigenemia, reduced residual fungal burden, and improved survival. There were no differences in phagocytic host response to A. terreus versus A. fumigatus; however, the rate of conidial germination of A. terreus was slower. The strain of A. terreus with the highest minimum inhibitory and minimum lethal concentration of AmB also had the lowest membrane ergosterol content. The hyphae of A. terreus in vivo displayed distinctive aleurioconidia, which may be a practical microscopic feature for rapid preliminary diagnosis.