RESUMO
The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46-68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%-100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06-1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%-8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.
Assuntos
Antifúngicos , Candida auris , Candidíase , Farmacorresistência Fúngica , Organização Mundial da Saúde , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase/microbiologia , Candidíase/epidemiologia , Candidíase/tratamento farmacológico , Candida auris/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Candidemia/epidemiologia , Candidemia/microbiologia , Candidemia/tratamento farmacológico , Surtos de Doenças , Candida/efeitos dos fármacos , Candida/classificação , Candida/isolamento & purificação , IncidênciaRESUMO
In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%-60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%-80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%-1%), amphotericin B (0%), and flucytosine (0%-4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.
Assuntos
Antifúngicos , Candida tropicalis , Farmacorresistência Fúngica , Organização Mundial da Saúde , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/isolamento & purificação , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candidíase Invasiva/epidemiologia , Candidíase Invasiva/microbiologia , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/mortalidade , Incidência , Saúde Global , Fatores de RiscoRESUMO
Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.
Assuntos
Antifúngicos , Aspergilose , Aspergillus fumigatus , Farmacorresistência Fúngica , Organização Mundial da Saúde , Humanos , Aspergillus fumigatus/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergilose/mortalidade , Voriconazol/farmacologia , Voriconazol/uso terapêutico , Incidência , Testes de Sensibilidade Microbiana , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/mortalidade , Infecções Fúngicas Invasivas/tratamento farmacológico , Fatores de RiscoRESUMO
In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (â¼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.
Assuntos
Antifúngicos , Farmacorresistência Fúngica , Pichia , Organização Mundial da Saúde , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Pichia/isolamento & purificação , Pichia/efeitos dos fármacos , Incidência , Fatores de Risco , Candidíase/epidemiologia , Candidíase/microbiologia , Candidíase/prevenção & controleRESUMO
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 µg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/µl compared with 24.26 when CD4 count <50 cells/µl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.
Assuntos
Antifúngicos , Coccidioides , Paracoccidioides , Talaromyces , Organização Mundial da Saúde , Talaromyces/isolamento & purificação , Talaromyces/classificação , Talaromyces/efeitos dos fármacos , Humanos , Paracoccidioides/isolamento & purificação , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/classificação , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Coccidioides/isolamento & purificação , Coccidioides/classificação , Coccidioides/efeitos dos fármacos , Micoses/epidemiologia , Micoses/microbiologia , Micoses/mortalidade , Paracoccidioidomicose/epidemiologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/tratamento farmacológico , Coccidioidomicose/epidemiologia , Coccidioidomicose/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.
Assuntos
Antifúngicos , Fusarium , Testes de Sensibilidade Microbiana , Scedosporium , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fusarium/efeitos dos fármacos , Fusarium/isolamento & purificação , Scedosporium/efeitos dos fármacos , Scedosporium/isolamento & purificação , Scedosporium/classificação , Organização Mundial da Saúde , Micoses/epidemiologia , Micoses/microbiologia , Fusariose/microbiologia , Fusariose/epidemiologia , Ascomicetos/efeitos dos fármacos , Infecções Fúngicas InvasivasRESUMO
PURPOSE: H. capsulatum is endemic in Indonesia, but the value of Histoplasma antigen detection has not been studied. PATIENTS AND METHODS: Histoplasma galactomannan (GM) ELISA was applied to sera of patients with unproven pulmonary tuberculosis (TB) and patients with a positive Aspergillus GM. Both Histoplasma and Aspergillus GM tests were performed to determine any possible cross-reaction with certain foods. RESULTS: Fourteen of 122 (11.5%) sera of patients with newly diagnosed clinical TB were positive for Histoplasma GM. The positivity rate in the serum of patients 5-6 and 12 months after TB diagnosis was 3.8% and 3.5%, respectively. Of 88 positive Aspergillus GM sera, 63 (71.6%) were also positive for Histoplasma GM. All tested foods were positive for Aspergillus GM, while 65% of foods were positive for Histoplasma GM. CONCLUSION: Galactomannan is widespread in sera and food in Jakarta, possibly related to food consumption. Histoplasma and Aspergillus antigen detection for the diagnosis will require additional means of confirming the diagnosis; negative tests may be more helpful for ruling out invasive histoplasmosis and aspergillosis.
Assuntos
Aspergilose , Histoplasmose , Humanos , Histoplasma , Indonésia , Histoplasmose/diagnóstico , Aspergilose/diagnóstico , Aspergillus , Antígenos de Fungos , Mananas/análise , Sensibilidade e EspecificidadeRESUMO
Chronic pulmonary fungal infections may occur in patients with previous history of pulmonary tuberculosis (TB), and are often clinically misclassified as TB, especially when bacteriological confirmation for Mycobacterium tuberculosis is absent. In this study, we investigated the prevalence of antibody against Histoplasma capsulatum and Aspergillus fumigatus in patients with confirmed and clinically chronic TB. Antibodies against H. capsulatum and A. fumigatus were measured from serum samples using enzyme-linked immunosorbent assay (ELISA). The presence M. tuberculosis in sputum was confirmed using smear microscopy, GeneXpert MTB/RIF assay, or culture. Antibodies against H. capsulatum and A. fumigatus were elevated in 16.9% and 26.9% of bacteriologically confirmed chronic TB patients, and 12.1% and 18.2% in those without bacteriological confirmation, respectively. Approximately one-third of patients who had positive anti-Histoplasma antibody also had elevated levels of antibody against Aspergillus fumigatus (P < .001). Our study highlights the importance of chronic pulmonary fungal infection in post-TB patients with recurrent respiratory symptoms.
This study describes the presence of antibodies against Aspergillus fumigatus and Histoplasma capsulatum in patient with pulmonary TB patients. Our study highlights the importance of chronic pulmonary fungal infections in post-TB patients with recurrent respiratory symptoms.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Aspergillus fumigatus , Histoplasma , Estudos Transversais , Indonésia , Sensibilidade e Especificidade , Tuberculose/diagnóstico , Tuberculose/veterinária , Anticorpos , Escarro/microbiologiaRESUMO
OBJECTIVES: Chronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary TB. CPA may also be misdiagnosed as bacteriologically negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia, a country with a high incidence of TB. METHODS: In this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0-8 weeks) and at the end (5-6 months) of TB therapy. CPA diagnosis was based on symptoms (≥3 months), characteristic radiological features and positive Aspergillus serology, and categorised as proven, probable and possible. RESULTS: Of the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence rates of proven and probable CPA at baseline were 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (two with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA. CONCLUSION: CPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.
Assuntos
Aspergilose Pulmonar , Tuberculose Pulmonar , Anticorpos Antifúngicos , Doença Crônica , Humanos , Imunoglobulina G , Indonésia/epidemiologia , Estudos Longitudinais , Infecção Persistente , Estudos Prospectivos , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/diagnóstico por imagemRESUMO
Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is widely used in clinical laboratories for routine identification of bacteria and yeasts. However, methodological difficulties are still apparent when applied to filamentous fungi. The liquid cultivation method recommended by Bruker Daltonics GmbH for identification of filamentous fungi by MALDI-TOF MS is labour intensive and time-consuming. In this study, growth of Aspergillus species on different (porous) surfaces was investigated with the aim to develop a more reliable, quicker and less laborious identification method using MALDI-TOF MS. Mycelial growth without sporulation mimicking liquid cultivation and reliable MALDI-TOF MS spectra were obtained when A. fumigatus strains were grown on and in between a polycarbonate membrane filter on Sabouraud dextrose agar. A database of in-house reference spectra was created by growing Aspergillus reference strains (mainly focusing on sections Fumigati and Flavi) under these selected conditions. A test set of 50 molecularly identified strains grown under different conditions was used to select the best growth condition for identification and to perform an initial validation of the in-house database. Based on these results, the cultivation method on top of a polycarbonate filter proved to be most successful for species identification. This method was therefore selected for the identification of two sets of clinical isolates that mainly consisted of Aspergilli (100 strains originating from Indonesia, 70 isolates from Qatar). The results showed that this cultivation method is reliable for identification of clinically relevant Aspergillus species, with 67% and 76% correct identification of strains from Indonesia and Qatar, respectively. In conclusion, cultivation of Aspergilli on top of a polycarbonate filter showed improved results compared to the liquid cultivation protocol recommended by Bruker in terms of percentage of correct identification, ease of MSP creation, time consumption, cost and labour intensity. This method can be reliably applied for identification of clinically important Aspergilli and has potential for identification of other filamentous fungi.
Assuntos
Aspergillus , Fungos , Lasers , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , LevedurasRESUMO
BACKGROUND: Indonesia is a tropical country, warm and humid, with numerous environmental fungi. Data on fungal disease burden help policymakers and clinicians. OBJECTIVES: We have estimated the incidence and prevalence of serious fungal diseases. METHODS: We found all published and unpublished data and estimated the incidence and prevalence of fungal diseases based on populations at risk. HIV data were derived from UNAIDS (2017), pulmonary tuberculosis (PTB) data from 2013-2019, data on chronic pulmonary aspergillosis (CPA) were used to estimate CPA prevalence and likely deaths, COPD data from Hammond (2020), lung cancer incidence was from Globocan 2018, and fungal rhinosinusitis was estimated using community data from India. RESULTS: Overall ~7.7 million Indonesians (2.89%) have a serious fungal infection each year. The annual incidence of cryptococcosis in AIDS was 7,540. Pneumocystis pneumonia incidence was estimated at 15,400 in HIV and an equal number in non-HIV patients. An estimated 1% and 0.2% of new AIDS patients have disseminated histoplasmosis or Talaromyces marneffei infection. The incidence of candidaemia is 26,710. The annual incidence of invasive aspergillosis was estimated at 49,500 and the prevalence of CPA is at 378,700 cases. Allergic bronchopulmonary aspergillosis prevalence in adults is estimated at 336,200, severe asthma with fungal sensitisation at 443,800, and fungal rhinosinusitis at 294,000. Recurrent vulvovaginal candidiasis is estimated at 5 million/year (15-50 years old). The incidence of fungal keratitis around 40,050. Tinea capitis prevalence in schoolchildren about 729,000. CONCLUSIONS: Indonesia has a high burden of fungal infections.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Síndrome da Imunodeficiência Adquirida , Candidemia , Micoses/epidemiologia , Aspergilose Pulmonar , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adolescente , Adulto , Candidemia/epidemiologia , Criança , Feminino , Fungos , Histoplasmose/epidemiologia , Humanos , Incidência , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Aspergilose Pulmonar/epidemiologia , Adulto JovemRESUMO
COVID-19 is a disease reported to suppress cellular immunity. This may lead to the development of opportunistic infections, among others black fungus, or mucormycosis. On the other hand, pre-existing defect in immunity may render patients susceptible to both mucormycosis and COVID-19. Mucormycosis is a relatively rare fungal infection with rapid progression unless diagnosed promptly and treated adequately, and urgent surgical and medical intervention is lifesaving. The manifestation of mucormycosis largely depends on the presence of exposure to the pathogen and the existing risk factor of the host. As black fungus is locally invasive, the majority of cases will involve tissue damage with local destruction and contiguous spread to nearby structure. We here with present a case of black fungus complicated with COVID-19 in a man with underlying non-Hodgkin's lymphoma.
Assuntos
COVID-19 , Linfoma não Hodgkin , Mucorales/isolamento & purificação , Mucormicose , Septo Nasal/patologia , SARS-CoV-2/isolamento & purificação , Adulto , Biópsia/métodos , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/fisiopatologia , COVID-19/terapia , Desbridamento/métodos , Progressão da Doença , Humanos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/fisiopatologia , Masculino , Mucormicose/complicações , Mucormicose/microbiologia , Mucormicose/patologia , Mucormicose/fisiopatologia , Doenças Nasais/microbiologia , Doenças Nasais/patologia , Isolamento de Pacientes/métodos , Tempo para o Tratamento , Tomografia Computadorizada por Raios X/métodosRESUMO
We performed morphology, molecular study and antifungal susceptibility test on 10 Talaromyces sp. isolates: eight clinical isolates (human immunodeficiency virus (HIV) and non-HIV-patient) and two isolates from rats. All strains produced red soluble pigment and microscopically showed Penicillium-like structure in room temperature and yeast-like structure in 37°C. Based on molecular analysis, nine isolates were identified as Talaromyces atroroseus (including the isolates from rats) and one as T. marneffei. Our susceptibility result of T. marneffei supports the use of amphotericin B, itraconazole for talaromycosis marneffei management. Talaromyces atroroseus showed variable MIC to echinocandin, azole derivatives, 5-flucytosine and amphotericin B.
Assuntos
Antifúngicos/farmacologia , Infecções por HIV/microbiologia , Talaromyces/classificação , Animais , Humanos , Indonésia , Testes de Sensibilidade Microbiana , Micoses/microbiologia , Pigmentação , Ratos/microbiologia , Talaromyces/efeitos dos fármacos , Talaromyces/genética , Talaromyces/isolamento & purificaçãoRESUMO
BACKGROUND: Systemic fungal infection (SFI) is one of leading causes of morbidity and mortality in very low birth weight (VLBW) preterm infants. Because early diagnosis of SFI is challenging due to nonspecific manifestations, prophylaxis becomes crucial. This study aimed to assess effectiveness of oral nystatin as an antifungal prophylaxis to prevent SFI in VLBW preterm infants. METHODS: A prospective, open-labelled, randomized controlled trial was performed in a neonatal intensive care unit (NICU) of an academic hospital in Indonesia. Infants with a gestational age ≤ 32 weeks and/or birth weight of ≤ 1500 g with risk factors for fungal infection were assessed for eligibility and randomized to either an intervention group (nystatin) or control group. The intervention group received 1 ml of oral nystatin three times a day, and the control group received a dose of 1 ml of sterile water three times a day. The incidence of fungal colonization and SFI were observed and evaluated during the six-week study period. Overall mortality rates and nystatin-related adverse drug reactions during the study period were also documented. RESULTS: A total of 95 patients were enrolled. The incidence of fungal colonization was lower among infants in nystatin group compared to those in control group (29.8 and 56.3%, respectively; relative risk 0.559; 95% confidence interval 0.357-0.899; p-value = 0.009). There were five cases of SFI, all of which were found in the control group (p-value = 0.056). There was no difference in overall mortality between the two groups. No adverse drug reactions were noted during the study period. CONCLUSIONS: Nystatin is effective and safe as an antifungal prophylactic medication in reducing colonization rates in the study population. Whilst the use of nystatin showed a potential protective effect against SFI among VLBW preterm infants, there was no statistical significant difference in SFI rates between groups. TRIAL REGISTRATION: NCT03390374. Registered 4 January 2018 - Retrospectively registered.
Assuntos
Doenças do Prematuro , Micoses , Antifúngicos/uso terapêutico , Fluconazol , Humanos , Indonésia , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/prevenção & controle , Recém-Nascido de muito Baixo Peso , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Nistatina/uso terapêutico , Estudos ProspectivosRESUMO
Talaromycosis is caused by the dimorphic fungus Talaromyces marneffei (formerly Penicillium marneffei) endemic in South and Southeast Asia. Its clinical similarity with other dimorphic fungal infections (sometimes) make the diagnosis challenging. We report an immunocompromised patient with talaromycosis mimicking histoplamosis. A 26-year-old HIV-positive man had suffered from rashes over the face, trunk, and extremities for three months. His physical examination showed centrally necrotic, ulcerated papules and nodules. A biopsied papule revealed granulomas containing numerous oval, yeast-like cells, some displaying central septation. Saboraud agar culture grew mold with diffuse red pigment consistent with T. marneffei. Careful histopathological examination and microbiological culture are important for the accurate diagnosis of fungal infections.
Assuntos
Infecções por HIV/imunologia , Histoplasmose/diagnóstico , Hospedeiro Imunocomprometido , Micoses/diagnóstico , Adulto , Antifúngicos/uso terapêutico , Técnicas de Cultura , Diagnóstico Diferencial , Humanos , Itraconazol/uso terapêutico , Masculino , Micoses/tratamento farmacológico , Micoses/imunologia , Micoses/patologiaRESUMO
An online survey of mycology laboratories in seven Asian countries was conducted to assess the status, competence, and services available. Country representatives from the Asia Fungal Working Group (AFWG) contacted as many laboratories performing mycology diagnosis as possible in their respective countries, requesting that the laboratory heads complete the online survey. In total, 241 laboratories responded, including 71 in China, 104 in India, 11 in Indonesia, 26 in the Philippines, four in Singapore, 18 in Taiwan, and seven in Thailand. Overall, 129/241 (53.5%) surveyed mycology laboratories operate as separate designated mycology laboratories, 75/241 (31.1%) conduct regular formal staff training, 103/241 (42.7%) are accredited, and 88/157 (56.1%) participate in external quality assurance scheme (EQAS) programs. Microscopy and culture methods are available in nearly all laboratories, although few perform DNA sequencing (37/219; 16.9%) or use matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) (27/219; 12.3%) for isolate identification. Antifungal susceptibility testing is performed in 142/241 (58.9%) laboratories, mainly for yeasts. The most commonly performed nonculture diagnostic is cryptococcal antigen testing (66 laboratories), followed by galactomannan testing (55), polymerase chain reaction (PCR) diagnosis (37), and beta-D-glucan testing (24). Therapeutic drug monitoring is conducted in 21 laboratories. There is almost no access to advanced diagnostic tests, like galactomannan, ß-D-glucan, and PCR, in the surveyed laboratories in Indonesia, the Philippines, and Thailand. These results highlight the need for development of quality laboratories, accreditation and training of manpower in existing laboratories, and access to advanced non-culture-based diagnostic tests to facilitate the diagnosis of fungal infections in Asia.
Assuntos
Fungos/isolamento & purificação , Laboratórios/estatística & dados numéricos , Técnicas de Tipagem Micológica/estatística & dados numéricos , Micologia/estatística & dados numéricos , Micoses/diagnóstico , Ásia , Países em Desenvolvimento , Fungos/classificação , Humanos , Agências Internacionais , Laboratórios/normas , Técnicas de Tipagem Micológica/normas , Micologia/instrumentação , Micologia/normas , Micoses/microbiologia , Inquéritos e QuestionáriosRESUMO
In Indonesia, 2.4% of all new tuberculosis patients had multi-drug resistant disease (MDR-TB); an estimated 24,000 incidences. Historical case series of MDR-TB described a high frequency of cavitation and poor prognosis. The diagnosis of chronic pulmonary aspergillosis (CPA) relies on raised levels of Aspergillus IgG antibodies, and detectable Histoplasma IgG antibodies are suspicious for chronic pulmonary histoplasmosis (CPH). We investigated whether MDR-TB patients might have concurrent CPH or CPA. This was a cross-sectional study with 50 MDR-TB patients. ELISA was used to detect Histoplasma IgG antibodies and lateral flow assay was used to detect Aspergillus IgG/IgM antibodies. Several other possible disease determinants were assessed by multivariate analysis. Of the 50 MDR-TB patients, 14 (28%) and 16 (32%) had positive Histoplasma or Aspergillus serology; six patients (12%) had dual antibody reactivity. Radiological abnormalities in positive patients included diffuse or local infiltrates, nodules, consolidation, and apical cavities, consistent with CPH and CPA. Patients with detectable fungal antibodies tended to have worse disease, and 4 of 26 (15.3%) died in the first 5 months of dual infection (p = 0.11 compared with no deaths in those with only MDR-TB). The criteria for the diagnosis of CPH and CPA were fulfilled in those with moderately and far advanced disease (13 of 14 or 93%) and 12 of 16 (75%), respectively. Damp housing was the only determinant associated with Histoplasma antibodies (PR 2.01; 95%CI 0.56-7.19), while pets were associated with the Aspergillus antibody (PR 18.024; 95%CI 1.594-203.744). CPA or CPH are probably frequent in MDR-TB patients in Indonesia and may carry a worse prognosis.
RESUMO
Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum, which in chronic conditions, is generally difficult to distinguish from pulmonary tuberculosis (TB) based on its clinical appearance; therefore, diagnostic errors could occur. Meanwhile, the prevalence of multidrug-resistant pulmonary TB (MDR-TB) in Indonesia remains high. Study determining the incidence of histoplasmosis in MDR-TB is unavailable worldwide. The aim of this study was to determine the risk factors of histoplasmosis incidence in MDR-TB patients in Indonesia. A cross-sectional was conducted at H. Adam Malik General Hospital, Medan, Indonesia and the ELISA platform (semi-quantitative) was used to detect histoplasma antibodies. Factors associated with histoplasmosis incidence among MDR-TB were determined using a Chi-squared test. A total of 50 MDR-TB patients were included this study of which 14 of them (28%) had histoplasmosis. The majority of histoplasmosis occurred in males, in MDR-TB patients with a history of TB treatment and among who had chest x-rays with far-advanced lesions. However, statistical analyses indicated none of those factors (sex, TB treatment history, status of the lung) as well as age group, acid-fast bacillus result, Mycobacterium tuberculosis culture result, having pet, living in damp house, working in the field or plantation, having HIV infection and smoking status were associated with histoplasmosis incidence. This study highlights that the incidence of histoplasmosis is relatively high and therefore further studies are important to be conducted in Indonesia that has a high MDR-TB cases.
RESUMO
The burden of invasive fungal infections associated with opportunistic fungal pathogens is a persistent challenge, particularly among people with advanced HIV disease. In October, 2022, WHO published the Fungal Priority Pathogens List (FPPL)-the first global effort to systematically prioritise fungal pathogens. Of the 19 pathogens in the WHO FPPL, four opportunistic pathogens in particular cause invasive diseases in people living with HIV: Cryptococcus neoformans, Histoplasma spp, Pneumocystis jirovecii, and Talaromyces marneffei. These four fungal pathogens are major causes of illness and death in people with advanced HIV and overwhelmingly affect those in low-income and middle-income countries. Access to diagnostics, improved surveillance, targeted support for innovation, and an enhanced public health focus on these diseases are needed in the effort to reduce HIV-associated deaths.
Assuntos
Infecções por HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HistoplasmaRESUMO
INTRODUCTION: Invasive fungal infections (IFIs) in Asia/Pacific are a particular threat to patients with malignancies, uncontrolled diabetes mellitus or undiagnosed/untreated human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS). Adequate and early access to diagnostic tools and antifungals is essential for IFI clinical management and patient survival. METHODS: Details on institution profile, self-perception on IFI, and access to microscopy, culture, serology, antigen detection, molecular testing, and therapeutic drug monitoring for IFI were collected in a survey. RESULTS: As of June 2022, 235 centres from 40 countries/territories in Asia/Pacific answered the questionnaire. More than half the centres were from six countries: India (25%), China (17%), Thailand (5%), Indonesia, Iran, and Japan (4% each). Candida spp. (93%) and Aspergillus spp. (75%) were considered the most relevant pathogens. Most institutions had access to microscopy (98%) or culture-based approaches (97%). Furthermore, 79% of centres had access to antigen detection, 66% to molecular assays, and 63% to antibody tests. Access to antifungals varied between countries/territories. At least one triazole was available in 93% of the reporting sites (voriconazole [89%] was the most common mould-active azole), whereas 80% had at least one amphotericin B formulation, and 72% had at least one echinocandin. CONCLUSION: According to the replies provided, the resources available for IFI diagnosis and management vary among Asia/Pacific countries/territories. Economical or geographical factors may play a key role in the incidence and clinical handling of this disease burden. Regional cooperation may be a good strategy to overcome shortcomings.