Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal St...Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.展开更多
BACKGROUND Methylmalonic acidemia(MMA)is characterized by non-specific symptoms such as vomiting,and feeding difficulties,along with delayed mental and physical development.However,no case of MMA combined with pulmona...BACKGROUND Methylmalonic acidemia(MMA)is characterized by non-specific symptoms such as vomiting,and feeding difficulties,along with delayed mental and physical development.However,no case of MMA combined with pulmonary fungal infection has been reported yet.CASE SUMMARY We report the case of a neonate who presented pulmonary fungal infection along with the non-specific features of MMA.Exome sequencing revealed a c.331C>T variant in exon 3 of MMACHC from the father,and a c.658-c.660delAAG variant in exon 4 from the mother,which confirmed the diagnosis of cblC type MMA combined with hyperhomocysteinemia.CONCLUSION Invasive fungal infection might occur in some infants with MMA.Therefore,early diagnosis is recommended for unexplained pulmonary infection.展开更多
Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest pa...Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.展开更多
With increasing morbidity and mortality from chronic liver disease and acute liver failure,the need for liver transplantation is on the rise.Most of these patients are extremely vulnerable to infections as they are im...With increasing morbidity and mortality from chronic liver disease and acute liver failure,the need for liver transplantation is on the rise.Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions.Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities,a major portion of these patients continue to be affected by post-transplant infections.Of these,fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose.This mini-review aims to discuss the incidence of fungal infections following liver transplantation,the different fungi involved,the risk factors,which predispose these patients to such infections,associated diagnostic challenges,and the role of prophylaxis.The population at risk is increasingly old and frail,suffering from various other co-morbid conditions,and needs special attention.To improve care and to decrease the burden of such infections,we need to identify the at-risk population with more robust clinical and diagnostic parameters.A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.展开更多
The increased incidence of invasive and opportunistic mycoses is probably related to the growth of the immunocompromised population, such as people living with HIV. This study is a literature review that aims to analy...The increased incidence of invasive and opportunistic mycoses is probably related to the growth of the immunocompromised population, such as people living with HIV. This study is a literature review that aims to analyze the frequency of invasive fungal infections in people living with HIV. In most studies evaluated, <em>Pneumocystis</em> pneumonia was the most frequent invasive fungal infection among people living with HIV, and cryptococcosis was the second most frequent. Invasive fungal infections are associated with greater morbidity and mortality in people living with HIV. The most important highlighted information is that the lack of epidemiological data on fungal infections in the studied populations was reported by most studies. Therefore, there is a need for further studies to assess the frequency of invasive fungal infection in people living with HIV, which may serve as subsidies for the implementation of strategies for the prevention and management, with a consequent increase in the quality of life and reduction of morbidity/mortality in this population.展开更多
Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for t...Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.展开更多
As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with m...As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with multi-organ involvement,intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C.neoformans infections.Because adequate accumulation of drugs at target organs and cells is still difficult to achieve,an effective delivery strategy is desperately required to treat these infections.Here,we report a bioresponsive micro-to-nano(MTN)system that effectively clears the C.neoformans in vivo.This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3(MMP-3)in infectious microenvironments(IMEs)and secreted protein acidic and rich in cysteine(SPARC)in several associated target cells.In this MTN system,bovine serum albumin(BSA,a natural ligand of SPARC)was used for the preparation of nanoparticles(NPs),and then microspheres were constructed by conjugation with a special linker,which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide.This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection,and then hydrolyzed into BSA NPs by MMP-3 in the IMEs.The NPs further targeted the lung tissue,brain and infected macrophages based on the overexpression of SPARC,reaching multiple targets and achieving efficient treatment.We have developed a size-tunable strategy where microspheres"shrink"to NPs in IMEs,which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.展开更多
Invasive fungal infection is one of the major complication of severe burns which can induce local or systemic inflammatory response and cause serious substantial damage to the patient. The incidence of fungal infectio...Invasive fungal infection is one of the major complication of severe burns which can induce local or systemic inflammatory response and cause serious substantial damage to the patient. The incidence of fungal infection for burn victims is increasing dramatically during recent years. This guideline, organized by Chinese Society of Burn Surgeons, aims to standardize the diagnosis, prevention and treatment of burn invasive fungal infection. It can be used as one of the tools for treatment of major burn patients.展开更多
Objectives:Invasive fungal infections(IFIs)are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation(HSCT).Surgical interventions may be...Objectives:Invasive fungal infections(IFIs)are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation(HSCT).Surgical interventions may be necessary to improve the survival outcomes of these patients.The aim of this study is to report a single-center experience using surgical intervention as adjunctive treatment for IFI in adult leukemia patients.Methods:A retrospective review was conducted to obtain clinical characteristics and outcomes of surgically managed IFI patients diagnosed between January 2005 and December 2015 in our center.Results:Nineteen acute leukemia patients,median age 46 years(range 19–65),underwent 20 surgical procedures as management for IFI.Three patients had proven IFI diagnoses prior to surgery.Sixteen patients underwent surgery for both diagnostic and therapeutic purposes.Post-surgery,the diagnostic yield for proven IFI increased by a factor of 5,and 15 patients had definitive IFI diagnoses.Surgical complications included 2 pleural effusions,4 pneumothoraxes,and 1 hydropneumothorax.The median duration of hospitalization for patients with complications was 9 days(range 3–64).Thirteen patients benefited overall from the procedure,3 had temporary clinical benefits,and 2 had progression of IFI.After surgery,the 3-month and 2-year overall survival rates were 89.5%and 57.9%,respectively.The median time from surgery to resumption of chemotherapy or HSCT was 25 days.Conclusions:Surgical interventions for IFI are feasible in selected leukemia patients,as they yield valuable information to guide antifungal therapy or enable therapeutic outcomes with acceptable risk,thereby allowing patients to proceed with curative chemotherapy and HSCT.展开更多
There has been an increasing incidence of fungal infections in recent years.Rarely joints are also affected by fungal infections.Mainly,these infections develop in prosthetic joints,but sometimes native joints are als...There has been an increasing incidence of fungal infections in recent years.Rarely joints are also affected by fungal infections.Mainly,these infections develop in prosthetic joints,but sometimes native joints are also involved.Candida infections are mostly reported,but patients may also develop infections secondary to non-Candida fungi,especially Aspergillus.Diagnosis and management of these infections is challenging and may involve multiple surgical interventions and prolonged antifungal therapy.Despite this,these infections are associated with high morbidity and mortality.This review described the clinical features,risk factors,and therapeutic interventions required to manage fungal arthritis.展开更多
Chromoblastomycosis(CBM)is a fungal disease,distributed in tropical and subtropical regions,affecting mainly rural workers.It is characterized by chronic skin lesions that may vary from nodular,tumorous,verrucous or p...Chromoblastomycosis(CBM)is a fungal disease,distributed in tropical and subtropical regions,affecting mainly rural workers.It is characterized by chronic skin lesions that may vary from nodular,tumorous,verrucous or plaque type.Associated constitutional symptoms are rarely found.The histological presentation may yield a pathognomonic feature,the Medlar(sclerotic)bodies,in which a typical brown to black pigment is depicted,explaining“copper pennies”as its alias.In this article,the case of a 56-year-old woman in the countryside of Brazil is reported,whose main complaint was a chronic leg ulcer for the past 8 years.The left leg had a large,partially ulcerated plaque lesion was found.Microbiological cultures were positive for the pathogen.Histological analysis demonstrated pseudoepitheliomatous hyperplasia,lymphohistiocytic infiltrate and sclerotic bodies(“copper pennies”).CBM’s epidemiological panorama,once established uniquely by geographical distribution,is transitioning to a global health issue,influenced by immunosuppressive conditions,global warming and migration.This scenario demands CBM to be widely considered as a differential diagnosis and may represent a clinical challenge in regions whose professionals have little expertise in infectious tropical diseases.展开更多
This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)i...This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)influence the susceptibility to pulmonary invasive fungal disease(IFD)in patients with acute myeloid leukemia(AML)from a Chinese Han population.Eight single nucleotide polymorphisms(SNPs)of Dectin-1(rs 16910526,rs3901533,and rs7309123),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)and MyD88(rs4988453 and rs4988457)in the genomic DNA of 172 adult AML patients were genotyped.Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group(EORTC/MSG)consensus guidelines.SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD.The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR(qRT-PCR),and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed.Two Dectin-1 intron SNPs(rs3901533 and rs7309123)were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population.Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model(G/T+G/G vs.T/T,OR:2.158;95%Cl:1.109-4.2,P=0.02),Dectin-1 rs3901533 G allele(OR:2.201;95%Cl:1.206-4.019,P=0.01),or Dectin-1 rs7309123 C allele(OR:1.919;95%Cl:1.047-3.518,P=0.03).There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs(rs 16910526),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)or MyDHH(rs4988453 and rs4988457).In conclusion,two Dectin-1 SNPs(rs3901533 and rs7309123)are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.展开更多
BACKGROUND Scedosporium apiospermum(S.apiospermum)is a clinically rare and aggressive fungus mainly found in contaminated water,wetlands,decaying plants,stagnant water,and potted plants in hospitals.The lung,bone,join...BACKGROUND Scedosporium apiospermum(S.apiospermum)is a clinically rare and aggressive fungus mainly found in contaminated water,wetlands,decaying plants,stagnant water,and potted plants in hospitals.The lung,bone,joint,eye,brain,skin,and other sites are easily infected,and there is a marked risk of misdiagnosis.There have been few case reports of infection by S.apiospermum of the lumbar vertebrae;most reports have focused on infection of the lung.CASE SUMMARY An otherwise healthy 60-year-old man presented with a 4-mo history of lumbosacral pain,stooping,and limited walking.The symptoms were significantly aggravated 10 d prior to hospitalization,and radiating pain in the back of his left lower leg developed,which was so severe that he could not walk.Movement of the lumbar spine was significantly limited,anterior flexion was about 30°;backward extension,right and left lateral curvature,and rotational mobility were about 10°;tenderness of the spinous processes of the lumbar 3-5 vertebrae was evident,and the muscle strength of both lower limbs was gradeⅣ.Imaging suggested bony destruction of the lumbar 3,4,and 5 vertebrae and sacral 1 vertebra;in addition,the corresponding intervertebral spaces were narrowed and the lumbar 5 vertebra was posteriorly displaced and unstable.Lumbar vertebral infection was also noted,and the possibility of lumbar tuberculosis was considered.We first performed surgical intervention on the lesioned lumbar vertebrae,cleared the infected lesion,and performed stable fixation of the lesioned vertebral body using a lumbar internal fixation device,which restored the stability of the lumbar vertebrae.Cytological and pathological examination of the lesioned tissue removed during surgery confirmed S.apiospermum infection of the lumbar vertebrae;on this basis,the patient was administered voriconazole.At the 6-mo followup,efficacy was significant,no drug-related side effects were observed,and imaging examination showed no evidence of recurrence.CONCLUSION S.apiospermum infection can occur in immunocompetent individuals with no history of near drowning.Voriconazole is effective for the treatment of S.apiospermum infection of the lumbar vertebrae for which it is suitable as the first-line therapy.展开更多
BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received ch...BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received chemotherapy.Fusariosis is a rare pathogenic fungus,it can lead to severely invasive Fusarium infections.Along with the increased rate of immune compromised patients,the incidence of invasive Fusarium infections has also increased from the past few years.Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection.CASE SUMMARY We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin,eyeball,and knee joint during the course of chemotherapy.We performed skin biopsy,microbial cultivation,and molecular biological identification,and the pathogenic fungus was finally confirmed to be Fusarium solani.The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily,and surgical debridement.Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery.The disseminated Fusarium solani infection eventually resolved,and there was no recurrence at the 3 mo follow-up.CONCLUSION Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection.These are important to prevent progression to a more aggressive infection.Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy.Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.展开更多
Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neurop...Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neuropsychiatric systemic lupus erythematosus.Two recipients developed Scedosporiosis after kidney transplantation from the same donor.Recipient 1 died of central nervous system infection due to S.boydii based on the clinical presentations,and the positive metagenomic next-generation sequencing(mNGS)and culture results for the cerebrospinal fluid.The other recipient with urinary tract obstruction due to S.boydii,which was identified through the positive culture and mNGS results of the removed stents,was successfully treated by stent replacement and voriconazole administration.Undiagnosed disseminated donor infection and the transmission of S.boydii should be given attention,particularly when the donor and recipients have primary immunodeficiency disease.The screening of donors and recipients for S.boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients,due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.展开更多
The rise in incidence rates of invasive candidiasis warrants an increase in atten-tion and efforts toward preventing and treating this virulent infection.Cardiac involvement is one of the most feared sequelae and has ...The rise in incidence rates of invasive candidiasis warrants an increase in atten-tion and efforts toward preventing and treating this virulent infection.Cardiac involvement is one of the most feared sequelae and has a poor prognosis.Despite the introduction of several novel antifungal agents over the past quarter century,complications and mortality rates due to Candida endocarditis have remained high.Although fungal endocarditis has a mechanism similar to bacterial endocar-ditis,no specific diagnostic criteria or algorithm exists to help guide its manage-ment.Furthermore,recent data has questioned the current guidelines recommen-ding a combined approach of antifungal agents with surgical valve or indwelling prostheses removal.With the emergence of multidrug-resistant Candida auris,a focus on improved prophylactic measures and management strategies is nece-ssary.展开更多
BACKGROUND Infections,including invasive fungal infections(IFIs),are among the leading causes of mortality in liver transplant recipients during the first year posttransplantation.AIM To investigate the epidemiology,c...BACKGROUND Infections,including invasive fungal infections(IFIs),are among the leading causes of mortality in liver transplant recipients during the first year posttransplantation.AIM To investigate the epidemiology,clinical manifestations,risk factors,treatment outcomes,and mortality rate of post-liver transplantation invasive aspergillosis(IA).METHODS In this case-control study,22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran,Iran,between 2014 and 2019.The control group comprised 38 patients without IA infection matched for age and sex.The information obtained included the baseline characteristics of liver transplant patients,operative reports,post-transplantation characteristics of both groups and information about the fungal infection of the patient group.RESULTS The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%.The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant,renal replacement therapy,antithymocyte globulin induction therapy,post-transplant bile leakage,posttransplant hepatic artery thrombosis,repeated surgery within 30 d after the transplant,bacterial pneumonia before the aspergillosis diagnosis,receiving systemic antibiotics before the aspergillus infection,cytomegalovirus infection,and duration of post-transplant hospitalization in the intensive care unit.The most prevalent form of infection was invasive pulmonary aspergillosis,and the most common chest computed tomography scan findings were nodules,pleural effusion,and the halo sign.In the case group,prophylactic antifungal therapy was administered more frequently than in the control group.The antifungal therapy response rate at 12 wk was 63.7%.The 3-and 12-mo mortality rates of the patients with IA were 36.4%and 45.4%,respectively(compared with the mortality rate of the control group in 12 mo,which was zero).CONCLUSION In this study,the prevalence of IA among liver transplant recipients was relatively low.However,it was one of the leading causes of mortality following liver transplantation.Targeted antifungal therapy may be a factor in the low incidence of infections at our facility.Identifying the risk factors of IFIs,maintaining an elevated level of clinical suspicion,and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.展开更多
Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immun...Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immunocompromised individuals and the elderly, particularly those with a history of diabetes mellitus. Diagnosis is challenging because of non-specific symptoms that lead to late detection and complications. This report discusses a case of SBO with multiple bilateral cranial nerve abnormalities and highlights the diagnostic and management challenges in high-risk individuals with subtle clinical signs. Case presentation: This report describes a 63-year-old patient with hypertension and diabetes who underwent surgical debridement of the left ear due to malignant otitis externa 4 months prior to presentation. The patient presented with significant dysarthria, dysphagia, ptosis of the left eye with double vision, and hearing impairment in the left ear. Examination revealed bilateral CN VI palsy, right CN VII palsy, left CN VIII palsy, and a right CN XII deficit. Initial tests were unremarkable, but a high Fungitell assay and a second review of the CT scan and MRI revealed a pathological process in the base of the skull involving bony structures and cranial nerves bilaterally, which helped diagnose SBO. The patient was subsequently discharged with oral voriconazole and continued his usual medications. The patient requested further management abroad, because he did not notice resolution of his symptoms. Surgical treatment was employed abroad to relieve his symptoms, as he recovered slowly. Conclusion: This case report underscores the importance of a multidisciplinary approach to address SBO. Collaboration between specialists in infectious diseases, otolaryngology, radiology, and neurology plays a pivotal role in achieving an accurate diagnosis and developing a tailored treatment plan. Although SBO may be infrequent, this case report highlights the need to maintain heightened clinical suspicion in high-risk individuals.展开更多
This case report presents an unusual and challenging diagnostic scenario involving a 72-year-old man who recently returned from a trip to Maui, Hawaii. While in Maui, the patient presented with a fever and fatigue tha...This case report presents an unusual and challenging diagnostic scenario involving a 72-year-old man who recently returned from a trip to Maui, Hawaii. While in Maui, the patient presented with a fever and fatigue that resolved spontaneously. However, he had an observable rash on his head and was given a steroid injection to resolve the rash. Later on his trip, the patient experienced a dry, nonproductive cough which resolved with a five-day course of prednisone. While visiting Michigan, the patient began to experience neck pain and visited Troy Beaumont Hospital for further treatment. Meningitis tests were negative. Vancomycin was given due to the detection of gram positive coccidioidomycosis in the culture, but this was later proven to be a contaminant. Coccidiomycosis does not initially have specific symptoms. Despite negative coccidioidomycosis antigen tests, the patient exhibited features more consistent with blastomycosis and cryptococcus, highlighting the complexities of diagnosing fungal infections with atypical presentations. The case emphasizes the importance of considering alternative fungal pathogens native to endemic regions and pursuing comprehensive diagnostic measures to establish an accurate diagnosis. Lastly, the discussion about recommendations for antifungal therapy and preventative measures for individuals at risk of respiratory fungal infections is critically important for the advancement of early detection of fungal infections.展开更多
文摘Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.
文摘BACKGROUND Methylmalonic acidemia(MMA)is characterized by non-specific symptoms such as vomiting,and feeding difficulties,along with delayed mental and physical development.However,no case of MMA combined with pulmonary fungal infection has been reported yet.CASE SUMMARY We report the case of a neonate who presented pulmonary fungal infection along with the non-specific features of MMA.Exome sequencing revealed a c.331C>T variant in exon 3 of MMACHC from the father,and a c.658-c.660delAAG variant in exon 4 from the mother,which confirmed the diagnosis of cblC type MMA combined with hyperhomocysteinemia.CONCLUSION Invasive fungal infection might occur in some infants with MMA.Therefore,early diagnosis is recommended for unexplained pulmonary infection.
文摘Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.
文摘With increasing morbidity and mortality from chronic liver disease and acute liver failure,the need for liver transplantation is on the rise.Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions.Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities,a major portion of these patients continue to be affected by post-transplant infections.Of these,fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose.This mini-review aims to discuss the incidence of fungal infections following liver transplantation,the different fungi involved,the risk factors,which predispose these patients to such infections,associated diagnostic challenges,and the role of prophylaxis.The population at risk is increasingly old and frail,suffering from various other co-morbid conditions,and needs special attention.To improve care and to decrease the burden of such infections,we need to identify the at-risk population with more robust clinical and diagnostic parameters.A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.
文摘The increased incidence of invasive and opportunistic mycoses is probably related to the growth of the immunocompromised population, such as people living with HIV. This study is a literature review that aims to analyze the frequency of invasive fungal infections in people living with HIV. In most studies evaluated, <em>Pneumocystis</em> pneumonia was the most frequent invasive fungal infection among people living with HIV, and cryptococcosis was the second most frequent. Invasive fungal infections are associated with greater morbidity and mortality in people living with HIV. The most important highlighted information is that the lack of epidemiological data on fungal infections in the studied populations was reported by most studies. Therefore, there is a need for further studies to assess the frequency of invasive fungal infection in people living with HIV, which may serve as subsidies for the implementation of strategies for the prevention and management, with a consequent increase in the quality of life and reduction of morbidity/mortality in this population.
基金supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782)the Double First-Class(CPU2018PZQ13,China)of the China Pharmaceutical University+3 种基金the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)the Guangdong Basic and Applied Basic Research Foundation,China(No.2020A1515010593)the Fundamental Research Funds for Central Universities(No.20ykpy111,China)
文摘Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.
基金supported by the National Natural Science Foundation of China(No.82073789,and 81673376)the project for Innovative Research Group at Higher Educational Institutions in Chongqing(CXQT20006,China)+1 种基金Chongqing Postgraduate Research and Innovation Project(CYB20106,China)CAS Interdiscipliary Innovation Team(China)。
文摘As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with multi-organ involvement,intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C.neoformans infections.Because adequate accumulation of drugs at target organs and cells is still difficult to achieve,an effective delivery strategy is desperately required to treat these infections.Here,we report a bioresponsive micro-to-nano(MTN)system that effectively clears the C.neoformans in vivo.This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3(MMP-3)in infectious microenvironments(IMEs)and secreted protein acidic and rich in cysteine(SPARC)in several associated target cells.In this MTN system,bovine serum albumin(BSA,a natural ligand of SPARC)was used for the preparation of nanoparticles(NPs),and then microspheres were constructed by conjugation with a special linker,which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide.This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection,and then hydrolyzed into BSA NPs by MMP-3 in the IMEs.The NPs further targeted the lung tissue,brain and infected macrophages based on the overexpression of SPARC,reaching multiple targets and achieving efficient treatment.We have developed a size-tunable strategy where microspheres"shrink"to NPs in IMEs,which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.
文摘Invasive fungal infection is one of the major complication of severe burns which can induce local or systemic inflammatory response and cause serious substantial damage to the patient. The incidence of fungal infection for burn victims is increasing dramatically during recent years. This guideline, organized by Chinese Society of Burn Surgeons, aims to standardize the diagnosis, prevention and treatment of burn invasive fungal infection. It can be used as one of the tools for treatment of major burn patients.
文摘Objectives:Invasive fungal infections(IFIs)are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation(HSCT).Surgical interventions may be necessary to improve the survival outcomes of these patients.The aim of this study is to report a single-center experience using surgical intervention as adjunctive treatment for IFI in adult leukemia patients.Methods:A retrospective review was conducted to obtain clinical characteristics and outcomes of surgically managed IFI patients diagnosed between January 2005 and December 2015 in our center.Results:Nineteen acute leukemia patients,median age 46 years(range 19–65),underwent 20 surgical procedures as management for IFI.Three patients had proven IFI diagnoses prior to surgery.Sixteen patients underwent surgery for both diagnostic and therapeutic purposes.Post-surgery,the diagnostic yield for proven IFI increased by a factor of 5,and 15 patients had definitive IFI diagnoses.Surgical complications included 2 pleural effusions,4 pneumothoraxes,and 1 hydropneumothorax.The median duration of hospitalization for patients with complications was 9 days(range 3–64).Thirteen patients benefited overall from the procedure,3 had temporary clinical benefits,and 2 had progression of IFI.After surgery,the 3-month and 2-year overall survival rates were 89.5%and 57.9%,respectively.The median time from surgery to resumption of chemotherapy or HSCT was 25 days.Conclusions:Surgical interventions for IFI are feasible in selected leukemia patients,as they yield valuable information to guide antifungal therapy or enable therapeutic outcomes with acceptable risk,thereby allowing patients to proceed with curative chemotherapy and HSCT.
文摘There has been an increasing incidence of fungal infections in recent years.Rarely joints are also affected by fungal infections.Mainly,these infections develop in prosthetic joints,but sometimes native joints are also involved.Candida infections are mostly reported,but patients may also develop infections secondary to non-Candida fungi,especially Aspergillus.Diagnosis and management of these infections is challenging and may involve multiple surgical interventions and prolonged antifungal therapy.Despite this,these infections are associated with high morbidity and mortality.This review described the clinical features,risk factors,and therapeutic interventions required to manage fungal arthritis.
文摘Chromoblastomycosis(CBM)is a fungal disease,distributed in tropical and subtropical regions,affecting mainly rural workers.It is characterized by chronic skin lesions that may vary from nodular,tumorous,verrucous or plaque type.Associated constitutional symptoms are rarely found.The histological presentation may yield a pathognomonic feature,the Medlar(sclerotic)bodies,in which a typical brown to black pigment is depicted,explaining“copper pennies”as its alias.In this article,the case of a 56-year-old woman in the countryside of Brazil is reported,whose main complaint was a chronic leg ulcer for the past 8 years.The left leg had a large,partially ulcerated plaque lesion was found.Microbiological cultures were positive for the pathogen.Histological analysis demonstrated pseudoepitheliomatous hyperplasia,lymphohistiocytic infiltrate and sclerotic bodies(“copper pennies”).CBM’s epidemiological panorama,once established uniquely by geographical distribution,is transitioning to a global health issue,influenced by immunosuppressive conditions,global warming and migration.This scenario demands CBM to be widely considered as a differential diagnosis and may represent a clinical challenge in regions whose professionals have little expertise in infectious tropical diseases.
基金the National Natural Science Foundation of China(No.81500105).
文摘This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)influence the susceptibility to pulmonary invasive fungal disease(IFD)in patients with acute myeloid leukemia(AML)from a Chinese Han population.Eight single nucleotide polymorphisms(SNPs)of Dectin-1(rs 16910526,rs3901533,and rs7309123),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)and MyD88(rs4988453 and rs4988457)in the genomic DNA of 172 adult AML patients were genotyped.Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group(EORTC/MSG)consensus guidelines.SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD.The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR(qRT-PCR),and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed.Two Dectin-1 intron SNPs(rs3901533 and rs7309123)were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population.Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model(G/T+G/G vs.T/T,OR:2.158;95%Cl:1.109-4.2,P=0.02),Dectin-1 rs3901533 G allele(OR:2.201;95%Cl:1.206-4.019,P=0.01),or Dectin-1 rs7309123 C allele(OR:1.919;95%Cl:1.047-3.518,P=0.03).There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs(rs 16910526),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)or MyDHH(rs4988453 and rs4988457).In conclusion,two Dectin-1 SNPs(rs3901533 and rs7309123)are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.
基金Supported by Chinese People’s Liberation Army Medical Technology Youth Training Program,No. 20QNPY071
文摘BACKGROUND Scedosporium apiospermum(S.apiospermum)is a clinically rare and aggressive fungus mainly found in contaminated water,wetlands,decaying plants,stagnant water,and potted plants in hospitals.The lung,bone,joint,eye,brain,skin,and other sites are easily infected,and there is a marked risk of misdiagnosis.There have been few case reports of infection by S.apiospermum of the lumbar vertebrae;most reports have focused on infection of the lung.CASE SUMMARY An otherwise healthy 60-year-old man presented with a 4-mo history of lumbosacral pain,stooping,and limited walking.The symptoms were significantly aggravated 10 d prior to hospitalization,and radiating pain in the back of his left lower leg developed,which was so severe that he could not walk.Movement of the lumbar spine was significantly limited,anterior flexion was about 30°;backward extension,right and left lateral curvature,and rotational mobility were about 10°;tenderness of the spinous processes of the lumbar 3-5 vertebrae was evident,and the muscle strength of both lower limbs was gradeⅣ.Imaging suggested bony destruction of the lumbar 3,4,and 5 vertebrae and sacral 1 vertebra;in addition,the corresponding intervertebral spaces were narrowed and the lumbar 5 vertebra was posteriorly displaced and unstable.Lumbar vertebral infection was also noted,and the possibility of lumbar tuberculosis was considered.We first performed surgical intervention on the lesioned lumbar vertebrae,cleared the infected lesion,and performed stable fixation of the lesioned vertebral body using a lumbar internal fixation device,which restored the stability of the lumbar vertebrae.Cytological and pathological examination of the lesioned tissue removed during surgery confirmed S.apiospermum infection of the lumbar vertebrae;on this basis,the patient was administered voriconazole.At the 6-mo followup,efficacy was significant,no drug-related side effects were observed,and imaging examination showed no evidence of recurrence.CONCLUSION S.apiospermum infection can occur in immunocompetent individuals with no history of near drowning.Voriconazole is effective for the treatment of S.apiospermum infection of the lumbar vertebrae for which it is suitable as the first-line therapy.
基金Supported by the Scientific Research Project of Peking University Shenzhen Hospital,No.JCYJ2018011the San-Ming Project of Medicine in Shenzhen,No.SZSM201812059.
文摘BACKGROUND In recent years,the rate of immunosuppressed patients has increased rapidly.Invasive fungal infections usually occur in these patients,especially those who have had hematological malignances and received chemotherapy.Fusariosis is a rare pathogenic fungus,it can lead to severely invasive Fusarium infections.Along with the increased rate of immune compromised patients,the incidence of invasive Fusarium infections has also increased from the past few years.Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection.CASE SUMMARY We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin,eyeball,and knee joint during the course of chemotherapy.We performed skin biopsy,microbial cultivation,and molecular biological identification,and the pathogenic fungus was finally confirmed to be Fusarium solani.The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily,and surgical debridement.Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery.The disseminated Fusarium solani infection eventually resolved,and there was no recurrence at the 3 mo follow-up.CONCLUSION Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection.These are important to prevent progression to a more aggressive infection.Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy.Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.
基金supported by National Key Clinical Specialty Construction Project(General Surgery).
文摘Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neuropsychiatric systemic lupus erythematosus.Two recipients developed Scedosporiosis after kidney transplantation from the same donor.Recipient 1 died of central nervous system infection due to S.boydii based on the clinical presentations,and the positive metagenomic next-generation sequencing(mNGS)and culture results for the cerebrospinal fluid.The other recipient with urinary tract obstruction due to S.boydii,which was identified through the positive culture and mNGS results of the removed stents,was successfully treated by stent replacement and voriconazole administration.Undiagnosed disseminated donor infection and the transmission of S.boydii should be given attention,particularly when the donor and recipients have primary immunodeficiency disease.The screening of donors and recipients for S.boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients,due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.
文摘The rise in incidence rates of invasive candidiasis warrants an increase in atten-tion and efforts toward preventing and treating this virulent infection.Cardiac involvement is one of the most feared sequelae and has a poor prognosis.Despite the introduction of several novel antifungal agents over the past quarter century,complications and mortality rates due to Candida endocarditis have remained high.Although fungal endocarditis has a mechanism similar to bacterial endocar-ditis,no specific diagnostic criteria or algorithm exists to help guide its manage-ment.Furthermore,recent data has questioned the current guidelines recommen-ding a combined approach of antifungal agents with surgical valve or indwelling prostheses removal.With the emergence of multidrug-resistant Candida auris,a focus on improved prophylactic measures and management strategies is nece-ssary.
文摘BACKGROUND Infections,including invasive fungal infections(IFIs),are among the leading causes of mortality in liver transplant recipients during the first year posttransplantation.AIM To investigate the epidemiology,clinical manifestations,risk factors,treatment outcomes,and mortality rate of post-liver transplantation invasive aspergillosis(IA).METHODS In this case-control study,22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran,Iran,between 2014 and 2019.The control group comprised 38 patients without IA infection matched for age and sex.The information obtained included the baseline characteristics of liver transplant patients,operative reports,post-transplantation characteristics of both groups and information about the fungal infection of the patient group.RESULTS The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%.The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant,renal replacement therapy,antithymocyte globulin induction therapy,post-transplant bile leakage,posttransplant hepatic artery thrombosis,repeated surgery within 30 d after the transplant,bacterial pneumonia before the aspergillosis diagnosis,receiving systemic antibiotics before the aspergillus infection,cytomegalovirus infection,and duration of post-transplant hospitalization in the intensive care unit.The most prevalent form of infection was invasive pulmonary aspergillosis,and the most common chest computed tomography scan findings were nodules,pleural effusion,and the halo sign.In the case group,prophylactic antifungal therapy was administered more frequently than in the control group.The antifungal therapy response rate at 12 wk was 63.7%.The 3-and 12-mo mortality rates of the patients with IA were 36.4%and 45.4%,respectively(compared with the mortality rate of the control group in 12 mo,which was zero).CONCLUSION In this study,the prevalence of IA among liver transplant recipients was relatively low.However,it was one of the leading causes of mortality following liver transplantation.Targeted antifungal therapy may be a factor in the low incidence of infections at our facility.Identifying the risk factors of IFIs,maintaining an elevated level of clinical suspicion,and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.
文摘Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immunocompromised individuals and the elderly, particularly those with a history of diabetes mellitus. Diagnosis is challenging because of non-specific symptoms that lead to late detection and complications. This report discusses a case of SBO with multiple bilateral cranial nerve abnormalities and highlights the diagnostic and management challenges in high-risk individuals with subtle clinical signs. Case presentation: This report describes a 63-year-old patient with hypertension and diabetes who underwent surgical debridement of the left ear due to malignant otitis externa 4 months prior to presentation. The patient presented with significant dysarthria, dysphagia, ptosis of the left eye with double vision, and hearing impairment in the left ear. Examination revealed bilateral CN VI palsy, right CN VII palsy, left CN VIII palsy, and a right CN XII deficit. Initial tests were unremarkable, but a high Fungitell assay and a second review of the CT scan and MRI revealed a pathological process in the base of the skull involving bony structures and cranial nerves bilaterally, which helped diagnose SBO. The patient was subsequently discharged with oral voriconazole and continued his usual medications. The patient requested further management abroad, because he did not notice resolution of his symptoms. Surgical treatment was employed abroad to relieve his symptoms, as he recovered slowly. Conclusion: This case report underscores the importance of a multidisciplinary approach to address SBO. Collaboration between specialists in infectious diseases, otolaryngology, radiology, and neurology plays a pivotal role in achieving an accurate diagnosis and developing a tailored treatment plan. Although SBO may be infrequent, this case report highlights the need to maintain heightened clinical suspicion in high-risk individuals.
文摘This case report presents an unusual and challenging diagnostic scenario involving a 72-year-old man who recently returned from a trip to Maui, Hawaii. While in Maui, the patient presented with a fever and fatigue that resolved spontaneously. However, he had an observable rash on his head and was given a steroid injection to resolve the rash. Later on his trip, the patient experienced a dry, nonproductive cough which resolved with a five-day course of prednisone. While visiting Michigan, the patient began to experience neck pain and visited Troy Beaumont Hospital for further treatment. Meningitis tests were negative. Vancomycin was given due to the detection of gram positive coccidioidomycosis in the culture, but this was later proven to be a contaminant. Coccidiomycosis does not initially have specific symptoms. Despite negative coccidioidomycosis antigen tests, the patient exhibited features more consistent with blastomycosis and cryptococcus, highlighting the complexities of diagnosing fungal infections with atypical presentations. The case emphasizes the importance of considering alternative fungal pathogens native to endemic regions and pursuing comprehensive diagnostic measures to establish an accurate diagnosis. Lastly, the discussion about recommendations for antifungal therapy and preventative measures for individuals at risk of respiratory fungal infections is critically important for the advancement of early detection of fungal infections.
