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1.
One Health ; 18: 100711, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38545429

RESUMO

Invasive fungal diseases are increasing globally, causing a large burden of disease in vulnerable populations. At the same time, antifungal resistance is rapidly emerging. Affordable nationwide and regional surveillance of fungal pathogens is needed. We have adapted a citizen-science methodology developed by a United Kingdom research group to study six key fungi in Vietnam, where there is no existing formal surveillance. These pathogens were ranked as high or critical in the World Health Organization fungal priority pathogens list and recognized as major disease-causing agents in Vietnam. Secondary school students (n = 90) in Hanoi were our citizen scientists, collecting soil (n = 90) and air (n = 90) samples for fungal identification and characterisation of drug-susceptibility in the laboratory. Pilot studies confirmed the effectiveness of our revised isolation procedure, which used selective culture media to improve the isolation of target fungi. Through active school and student involvement, optimized protocols, and our cost-effective sampling, the study could be scaled across Vietnam. We demonstrate an approach to fungal surveillance which also enhances science education, and awareness of fungal diseases. It addresses critical healthcare and education challenges in Vietnam while combating the growing issues of invasive fungal diseases and antifungal resistance.

2.
Lancet Infect Dis ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38346436

RESUMO

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

4.
Lancet Reg Health West Pac ; 40: 100888, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37701716

RESUMO

Background: New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice. Methods: The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017-December 2020). Descriptive analyses were used to report patients' demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM). Findings: Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria - 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51-69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non-Aspergillus fumigatus species complex. Azole-resistance was present in 3/46 (6.5%) of A. fumigatus sensu stricto isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04-3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93-8.17, p < 0.001) but not neutropenia (HR 1.45; 95% CI 0.88-2.39, p = 0.135) were associated with mortality. Chronic kidney disease was also a significant predictor of death in the HM subgroup (HR 3.94; 95% CI 1.15-13.44, p = 0.028). Interpretation: IA is identified in high number of patients with mild/no immunosuppression in our study. The relatively high proportion of non-A. fumigatus species complex isolates and 6.5% azole-resistance rate amongst A. fumigatus sensu stricto necessitates accurate species identification and susceptibility testing for optimal patient outcomes. Funding: This work is unfunded. All authors' financial disclosures are listed in detail at the end of the manuscript.

5.
J Fungi (Basel) ; 9(6)2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37367595

RESUMO

Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with current antifungal therapies. Current diagnostic methods have inadequate sensitivity and specificity and may have issues with accessibility or turnaround time. Patients with diabetes mellitus and immune compromise are predisposed to infection with these environmental fungi, but COVID-19 has established itself as a new risk factor. Mucorales also cause healthcare-associated outbreaks, and clusters associated with natural disasters have also been identified. Robust epidemiological surveillance into burden of disease, at-risk populations, and emerging pathogens is required. Emerging serological and molecular techniques may offer a faster route to diagnosis, while newly developed antifungal agents show promise in preliminary studies. Equitable access to these emerging diagnostic techniques and antifungal therapies will be key in identifying and treating mucormycosis, as delayed initiation of therapy is associated with higher mortality.

6.
Metabolites ; 13(4)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37110238

RESUMO

The number of Candida spp. infections and drug resistance are dramatically increasing worldwide, particularly among immunosuppressed patients, and it is urgent to find novel compounds with antifungal activity. In this work, the antifungal and antibiofilm activity of thymoquinone (TQ), a key bioactive constituent of black cumin seed Nigella sativa L., was evaluated against Candida glabrata, a WHO 'high-priority' pathogen. Then, its effect on the expression of C. glabrata EPA6 and EPA7 genes (related to biofilm adhesion and development, respectively) were analyzed. Swab samples were taken from the oral cavity of 90 hospitalized patients in ICU wards, transferred to sterile falcon tubes, and cultured on Sabouraud Dextrose Agar (SDA) and Chromagar Candida for presumptive identification. Next, a 21-plex PCR was carried out for the confirmation of species level. C. glabrata isolates underwent antifungal drug susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), amphotericin B (AMB), and TQ according to the CLSI microdilution method (M27, A3/S4). Biofilm formation was measured by an MTT assay. EPA6 and EPA7 gene expression was assessed by real-time PCR. From the 90 swab samples, 40 isolates were identified as C. glabrata with the 21-plex PCR. Most isolates were resistant to FLZ (n = 29, 72.5%), whereas 12.5% and 5% were ITZ and AMB resistant, respectively. The minimum inhibitory concentration (MIC50) of TQ against C. glabrata was 50 µg/mL. Importantly, TQ significantly inhibited the biofilm formation of C. glabrata isolates, and EPA6 gene expression was reduced significantly at MIC50 concentration of TQ. TQ seems to have some antifungal, antibiofilm (adhesion) effect on C. glabrata isolates, showing that this plant secondary metabolite is a promising agent to overcome Candida infections, especially oral candidiasis.

7.
Lancet Reg Health West Pac ; 30: 100668, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36748068

RESUMO

Background: Drug outlets are a vital first point of healthcare contact in low- and middle-income countries (LMICs), but they are often poorly regulated and counter staff may be unqualified to provide advice. This introduces the risk of easy access to potentially harmful products, including unnecessary antimicrobials. Over-the-counter antimicrobial sales are a major driver of antimicrobial resistance (AMR) in LMICs. We aimed to investigate the distribution of different types of drug outlets and their association with socio-economic factors. Methods: We mapped the location of drug outlets in 40 randomly selected geographic clusters, covering a population of 1.96 million people. Data including type of drug outlet, context, operating hours, chief pharmacist name and qualification, and business registration identification were collected from mandatory public signage. We describe the density of drug outlets and levels of staff qualifications in relation to population density, urban vs rural areas, and poverty indices. Findings: We characterised 1972 drug outlets. In the study area, there was an average of 102 outlets/per 100,000 population, compared to the global average of 25. Predictably, population density was correlated with the density of drug outlets. We found that drug outlets were less accessible in rural vs urban areas, and for the poor. Furthermore, for these populations, degree-qualified pharmacists were less accessible and public signage frequently lacked mandatory registration information. Interpretation: Drug outlets appear over-supplied in Vietnam compared to other countries. Unregistered outlets and outlets without degree-qualified pharmacists are prevalent, especially in poor and rural areas, posing a risk for inappropriate supply of antimicrobials, which may contribute to AMR, and raises questions of equitable healthcare access. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.

8.
Mycoses ; 66(4): 346-353, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36564981

RESUMO

BACKGROUND: Anecdotally, the burden of fungal diseases in Vietnam is rapidly rising, but there has been no updated estimate on this issue since a previous report in 2015. OBJECTIVES: In this study, we aimed at estimating the incidence and prevalence of serious fungal infections for the year 2020. METHODS: We made estimates with a previously described methodology, using reports on the incidence and prevalence of various established risk factors for fungal infections from local, regional or global sources. RESULTS: We estimated 2,389,661 cases of serious fungal infection occurred in Vietnam in 2020. The most common condition was recurrent vaginal candidiasis (4047/100,000 women annually). Among people living with HIV, we estimated 451 cases of cryptococcal meningitis, 1030 of pneumocystis pneumonia, 166 of histoplasmosis and 1612 of talaromycosis annually. Candidaemia incidence was estimated at 12/100,000 population each year. Owing to its high burden of tuberculosis and respiratory diseases, Vietnam had high rates of severe infections caused by Aspergillus species. Incidence of invasive aspergillosis is 24/100,000 population, allergic bronchopulmonary aspergillosis 78/100,000 and severe asthma with fungal sensitisation 102/100,000. Five-year period prevalence of chronic pulmonary aspergillosis is 120/100,000 population /5-year period. Mucormycosis, fungal keratitis and tinea capitis were estimated at 192, 14,431 and 201 episodes each year, respectively. CONCLUSIONS: The number of patients with mycoses in Vietnam is likely underestimated due to a lack of local data and limited diagnostic capacity, but at least 2.5% of the population might have some form of serious fungal disease.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Aspergilose , Candidemia , Pneumonia por Pneumocystis , Humanos , Feminino , Vietnã/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Aspergilose/microbiologia , Pneumonia por Pneumocystis/microbiologia , Candidemia/epidemiologia , Prevalência , Incidência
9.
J Fungi (Basel) ; 8(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36354923

RESUMO

Pulmonary cryptococcosis describes an invasive lung mycosis caused by Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as pulmonary malignancy, leading to a delay in therapy. Epidemiology follows that of cryptococcal meningoencephalitis, with C. gattii infection more common in certain geographic regions. Diagnostic tools include histopathology, microscopy and culture, and the detection of cryptococcal polysaccharide antigen or Cryptococcus-derived nucleic acids. All patients with lung cryptococcosis should have a lumbar puncture and cerebral imaging to exclude central nervous system disease. Radiology is key, both as an adjunct to laboratory testing and as the initial means of detection in asymptomatic patients or those with non-specific symptoms. Pulmonary cryptococcomas (single or multiple) may also be associated with disseminated disease and/or cryptococcal meningitis, requiring prolonged treatment regimens. Optimal management for severe disease requires extended induction (amphotericin B and flucytosine) and consolidation therapy (fluconazole) with close clinical monitoring. Susceptibility testing is of value for epidemiology and in regions where relatively high minimum inhibitory concentrations to azoles (particularly fluconazole) have been noted. Novel diagnostic tools and therapeutic agents promise to improve the detection and treatment of cryptococcosis, particularly in low-income settings where the disease burden is high.

10.
BMJ Open ; 12(6): e052633, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732397

RESUMO

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem globally. Long, complex treatment regimens coupled with frequent adverse events have resulted in poor treatment adherence and patient outcomes. Smartphone-based mobile health (mHealth) technologies offer national TB programmes an appealing platform to improve patient care and management; however, clinical trial evidence to support their use is lacking. This trial will test the hypothesis that an mHealth intervention can improve treatment success among patients with MDR-TB and is cost-effective compared with standard practice. METHODS AND ANALYSIS: A community-based, open-label, parallel-group randomised controlled trial will be conducted among patients treated for MDR-TB in seven provinces of Vietnam. Patients commencing therapy for microbiologically confirmed rifampicin-resistant or multidrug-resistant tuberculosis within the past 30 days will be recruited to the study. Participants will be individually randomised to an intervention arm, comprising use of an mHealth application for treatment support, or a 'standard care' arm. In both arms, patients will be managed by the national TB programme according to current national treatment guidelines. The primary outcome measure of effectiveness will be the proportion of patients with treatment success (defined as treatment completion and/or bacteriological cure) after 24 months. A marginal Poisson regression model estimated via a generalised estimating equation will be used to test the effect of the intervention on treatment success. A prospective microcosting of the intervention and within-trial cost-effectiveness analysis will also be undertaken from a societal perspective. Cost-effectiveness will be presented as an incremental cost per patient successfully treated and an incremental cost per quality-adjusted life-year gained. ETHICS: Ethical approval for the study was granted by The University of Sydney Human Research Ethics Committee (2019/676). DISSEMINATION: Study findings will be disseminated to participants and published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: ACTRN12620000681954.


Assuntos
Telemedicina , Tuberculose Resistente a Múltiplos Medicamentos , Análise Custo-Benefício , Humanos , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Vietnã
11.
Lancet Reg Health West Pac ; 23: 100447, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35465041

RESUMO

Background: This study aimed to evaluate the appropriateness of antibiotic dispensing of private pharmacies in Vietnam. Methods: Standardised patient surveys were conducted in randomly selected community pharmacies across 40 districts in Vietnam. Four clinical scenarios were represented by patient actors: (a) an adult requesting treatment for a sibling with a viral upper respiratory tract infection (URTI), (b) a parent requesting treatment for a child with acute diarrhoea, (c) an adult making a direct antibiotic request, and (d) an adult presenting with an antibiotic prescription. We calculated the proportion of interactions that resulted in inappropriate supply of antibiotics and patient advice. Predictors of inappropriate antibiotic supply were assessed. Findings: Patient actors attended 949 pharmacies, resulting in 1266 clinical interactions. Antibiotics were inappropriately supplied to 92% (291/316) of adults requesting treatment for URTI symptoms, 43% (135/316) for children with acute diarrhoea symptoms and to 84% (267/317) of direct request for antibiotics. Only 49% of pharmacies advised patients regarding their antibiotic use. Female actors were more likely to be given antibiotics than male actors for URTI (aOR 2·71, 1·12-6·60) but not for diarrhoeal disease. Pharmacies in northern Vietnam were more likely than those in southern Vietnam to supply antibiotics without a prescription: for adult URTI (aOR=5·8, 95% CI: 2·2-14·9) and childhood diarrhoea (aOR=3·5, 95% CI: 2·0-6·0) symptoms, but less likely to dispense for direct antibiotics request. Interpretation: Inappropriate antibiotic supply was common in Vietnamese private pharmacies. Multifaceted measures are urgently needed to achieve WHO's global action plan for the optimal use of antimicrobials. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.

12.
Br J Clin Pharmacol ; 88(7): 3114-3131, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35229890

RESUMO

Understanding how pharmaceutical opioids and antipyretic analgesics interact with the immune system potentially has major clinical implications for management of patients with infectious diseases and surgical and critical care patients. An electronic search was carried out on MEDLINE, EMBASE, PsycINFO, CENTRAL and the Cochrane library to identify reports describing the immunomodulatory effects of opioid analgesics and antipyretic analgesics, and their effects in infectious diseases. In adaptive immunity, nonsteroidal anti-inflammatory drugs have divergent effects: augmenting cell-mediated immunity but inhibiting humoral immunity. Nonsteroidal anti-inflammatory drugs have demonstrated a beneficial role in Mycobacterium tuberculosis infection and histoplasmosis in animals, and may be plausible adjuvants to antimicrobial agents in these diseases. There is a need to evaluate these findings rigorously in human clinical trials. There is preliminary evidence demonstrating antiviral effects of indomethacin in SARS CoV-2 in vitro; however, uncertainty regarding its clinical benefit in humans needs to be resolved in large clinical trials. Certain opioid analgesics are associated with immunosuppressive effects, with a developing understanding that fentanyl, morphine, methadone and buprenorphine suppress innate immunity, whilst having diverse effects on adaptive immunity. Morphine suppresses key cells of the innate immunity and is associated with greater risk of infection in the postsurgical setting. Efforts are needed to achieve adequate analgesia whilst avoiding suppression of the innate immunity in the immediate postoperative period caused by certain opioids, particularly in cancer surgery.


Assuntos
Antipiréticos , Tratamento Farmacológico da COVID-19 , Doenças Transmissíveis , Analgésicos , Analgésicos Opioides/farmacologia , Analgésicos Opioides/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antipiréticos/farmacologia , Antipiréticos/uso terapêutico , Humanos , Morfina , Preparações Farmacêuticas
13.
Emerg Infect Dis ; 28(3): 684-692, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35202526

RESUMO

We evaluated the effects of the coronavirus disease pandemic on diagnosis of and treatment for tuberculosis (TB) in Vietnam. We obtained quarterly notifications for TB and multidrug-resistant/rifampin-resistant (MDR/RR) TB from 2015-2020 and evaluated changes in monthly TB case notifications. We used an interrupted time series to assess the change in notifications and treatment outcomes. Overall, TB case notifications were 8% lower in 2020 than in 2019; MDR/RR TB notifications were 1% lower. TB case notifications decreased by 364 (95% CI -1,236 to 508) notifications per quarter and MDR/RR TB by 1 (95% CI -129 to 132) notification per quarter. The proportion of successful TB treatment outcomes decreased by 0.1% per quarter (95% CI -1.1% to 0.8%) in 2020 compared with previous years. Our study suggests that Vietnam was able to maintain its TB response in 2020, despite the pandemic.


Assuntos
COVID-19 , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Antituberculosos/uso terapêutico , COVID-19/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Vietnã/epidemiologia
14.
J Fungi (Basel) ; 8(2)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35205864

RESUMO

Chronic pulmonary aspergillosis (CPA) is a fungal lung infection associated with high morbidity and mortality. Yet, it remains under-recognized worldwide, with few Australian clinical data available. This retrospective study aimed to investigate CPA at a major tertiary referral hospital in Sydney. We identified patients having International Classification of Diseases (ICD-10) codes for "aspergillosis" and/or positive respiratory microbiology samples for Aspergillus species from January 2012-December 2018 at Westmead Hospital. Eligible cases were classified using European Respiratory Society 2016 CPA guidelines. We diagnosed 28 CPA patients: median age 60 years (IQR: 57-66), with 17 (60.7%) being males. Most had chronic cavitary pulmonary aspergillosis phenotype (n = 17, 60.7%). Twenty-three patients had outcomes data returned. Nineteen (82.6%) received antifungal therapy (median duration: 10.5 months (IQR: 6.5-20.7)). Eight (34.7%) patients received <6 months of antifungals, including three (38%) deaths. Two (13%) patients receiving ≥6 months of antifungals died. Chronic obstructive pulmonary disease (COPD) (n = 9, 32.1%) was the leading predisposing factor for CPA in our cohort. This contrasts with the global picture, where prior tuberculosis generally predominates, but is similar to findings from other high-income countries. Nevertheless, further larger-scale studies are required to determine whether these results are generalizable to the wider Australian population.

15.
Front Public Health ; 10: 1048317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36743159

RESUMO

The reality of human induced climate change is no longer in doubt, but the concerted global action required to address this existential crisis remains inexcusably inert. Together with climate change, biodiversity collapse is increasingly driving the emergence and spread of infectious diseases, the consequences of which are inequitable globally. Climate change is regressive in its nature, with those least responsible for destroying planetary health at greatest risk of suffering the direct and indirect health consequences. Over half a billion of the world's children live in areas vulnerable to extreme weather events. Without immediate action, the health of today's children and future generations will be compromised. We consider the impact of biodiversity collapse on the spread of infectious diseases and outline a duty of care along a continuum of three dimensions of medical ethics. From a medical perspective, the first dimension requires doctors to serve the best interests of their individual patients. The second dimension considers the public health dimension with a focus on disease control and cost-effectiveness. The neglected third dimension considers our mutual obligation to the future health and wellbeing of children and generations to come. Given the adverse impact of our ecological footprint on current and future human health, we have a collective moral obligation to act.


Assuntos
Mudança Climática , Doenças Transmissíveis , Humanos , Criança , Biodiversidade , Saúde Pública
16.
J Fungi (Basel) ; 9(1)2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36675862

RESUMO

Cryptococcus species are a major cause of life-threatening infections in immunocompromised and immunocompetent hosts. While most disease is caused by Cryptococcus neoformans, Cryptococcus gattii, a genotypically and phenotypically distinct species, is responsible for 11-33% of global cases of cryptococcosis. Despite best treatment, C. gattii infections are associated with early mortality rates of 10-25%. The World Health Organization's recently released Fungal Priority Pathogen List classified C. gattii as a medium-priority pathogen due to the lack of effective therapies and robust clinical and epidemiological data. This narrative review summarizes the latest research on the taxonomy, epidemiology, pathogenesis, laboratory testing, and management of C. gattii infections.

17.
Intern Med J ; 51 Suppl 7: 118-142, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34937137

RESUMO

Cryptococcosis caused by the Cryptococcus neoformans-Cryptococcus gattii complex is an important opportunistic infection in people with immunodeficiency, including in the haematology/oncology setting. This may manifest clinically as cryptococcal meningitis or pulmonary cryptococcosis, or be detected incidentally by cryptococcal antigenemia, a positive sputum culture or radiological imaging. Non-Candida, non-Cryptococcus spp. rare yeast fungaemia are increasingly common in this population. These consensus guidelines aim to provide clinicians working in the Australian and New Zealand haematology/oncology setting with clear guiding principles and practical recommendations for the management of cryptococcosis, while also highlighting important and emerging rare yeast infections and their recommended management.


Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Hematologia , Austrália/epidemiologia , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Humanos , Saccharomyces cerevisiae
18.
BMJ Glob Health ; 6(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34615661

RESUMO

BACKGROUND: Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB. METHODS: A cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs' referral. RESULTS: In total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan. CONCLUSIONS: Few SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings.


Assuntos
Farmácias , Farmácia , Tuberculose , Estudos Transversais , Humanos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Vietnã/epidemiologia
19.
Elife ; 102021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581270

RESUMO

Background: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential. Methods: Open label randomized controlled trial. Participants received standard care - amphotericin combined with fluconazole for the first 2 weeks - or standard care plus tamoxifen 300 mg/day. The primary end point was Early Fungicidal Activity (EFA) - the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031. Results: Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (-0.48log10 colony-forming units/mL/CSF control arm versus -0.49 tamoxifen arm, difference -0.005log10CFU/ml/day, 95% CI: -0.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation. Conclusions: High-dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed. Funding: The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.


Assuntos
Anfotericina B/uso terapêutico , Cryptococcus neoformans/efeitos dos fármacos , Fluconazol/uso terapêutico , Meningite Criptocócica/tratamento farmacológico , Tamoxifeno/uso terapêutico , Adulto , Antifúngicos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Síndrome do QT Longo/induzido quimicamente , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/metabolismo , Tamoxifeno/efeitos adversos
20.
Clin Case Rep ; 9(6): e04314, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34194801

RESUMO

In patients with fulminant tricuspid valve infective endocarditis precluded from cardiothoracic intervention based on comorbidities or clinical status, percutaneous vegetation debulking utilizing the AngioJet rheolytic catheter system appears a viable rescue option to achieve source control.

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