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Cureus Jul 2023Histoplasmosis is a mycosis caused by , a dimorphic fungus endemic to areas with nitrogen-rich soil, like the one contaminated with bird and bat excrement. Patients with...
Histoplasmosis is a mycosis caused by , a dimorphic fungus endemic to areas with nitrogen-rich soil, like the one contaminated with bird and bat excrement. Patients with a deficient immune response are especially at risk for developing invasive infections, such as disseminated histoplasmosis, and secondary immunodeficiency can be a consequence of malnutrition. This case report presents a 15-month-old male infant with malnutrition who presented with signs and symptoms of disseminated histoplasmosis, including fever, malaise, weight loss, cough, and diarrhea. The infant came from a geographic area where histoplasmosis is endemic, and he was a member of a cultural group with a higher prevalence of histoplasmosis than the general population. On physical examination, hepatosplenomegaly, lymphadenopathy, and lung crackles were found, which are common in most patients with histoplasmosis. The keystone of diagnosis of infection is antigen detection, but the criterion standard is isolation of the organism from body specimens through laboratory culture. Histological diagnosis is especially useful for rapid diagnosis. Treatment of disseminated histoplasmosis in the pediatric population consists of deoxycholate amphotericin B for four to six weeks followed by itraconazole to complete a total of three months of treatment. Despite the involvement of multiple organ systems, the patient recovered satisfactorily after the completion of amphotericin B treatment for one month and the resolution of his malnourishment.
PubMed: 37551207
DOI: 10.7759/cureus.41493 -
Open Forum Infectious Diseases Oct 2023Inclusion of in the World Health Organization's first Fungal Priority Pathogens List under "high-priority" fungal species highlights the need for robust surveillance of...
BACKGROUND
Inclusion of in the World Health Organization's first Fungal Priority Pathogens List under "high-priority" fungal species highlights the need for robust surveillance of spp. in endemic and underrepresented regions. Despite increasing reports of histoplasmosis in Africa, data on the burden of this fungal disease are sparse in The Gambia. This baseline study examined the human seroprevalence of anti- antibody in a TB patient group in The Gambia, explored associations between seropositivity and demographic and clinical variables, and proposes future research directions.
METHODS
Biobanked plasma samples were selected from active TB cases with variable HIV infection status. Latex agglutination tests were performed on samples from 52 study participants to detect the presence of anti- antibodies. Potential risk factors for exposure were explored using logistic regression analysis.
RESULTS
The sample seroprevalence of anti- antibody was 28.8% (n = 15/52; 95% CI, 17.1%-43.1%). Multivariable logistic regression analysis identified a statistically significant association between seropositivity and age (odds ratio, 0.91; 95% CI, 0.84-0.98; = .008).
CONCLUSIONS
This baseline study provides evidence of seropositivity in TB patients in The Gambia and explores risk factors for exposure. The small sample size and use of the LAT in TB and HIV-positive patient groups are significant study limitations. Future research directions are proposed to ascertain the burden of in general and patient populations and explore the context-specific risk factors for exposure and infection in The Gambia.
PubMed: 37901120
DOI: 10.1093/ofid/ofad510 -
Pathogens (Basel, Switzerland) Aug 2023Histoplasmosis is an endemic mycosis in the Americas. However, its diagnosis is challenging due to the complexity and limited availability of conventional laboratory...
Histoplasmosis is an endemic mycosis in the Americas. However, its diagnosis is challenging due to the complexity and limited availability of conventional laboratory techniques-antigen tests, culture, and staining. Microscopic preparations often confuse with other pathogens, such as spp. The genus comprises three varieties: var. , var. , and var. , which cannot be distinguished using conventional techniques. An infant from a tropical region of Ecuador was hospitalized for fever, bloody diarrhea, and anemia persisting for two months. Upon admission, he received antibiotics and immunosuppressants. Histopathological examination of the lymph nodes, intestines, and bone marrow aspirate reported the presence of -like amastigotes, and treatment was initiated with meglumine antimoniate and conventional amphotericin B. However, subsequent analysis of samples using PCR and DNA sequencing identified var. but not . Despite fluconazole and amphotericin B, the infant succumbed to the disease. The delay in clinical and laboratory diagnosis of histoplasmosis and the use of nonspecific and ineffective drugs such as fluconazole led to disease dissemination and, ultimately, death. Implementing molecular diagnosis and antigen tests in laboratories located in endemic regions and reference hospitals is crucial.
PubMed: 37764920
DOI: 10.3390/pathogens12091112 -
Cureus Dec 2023Histoplasmosis is a systemic mycosis caused by (). Systemic involvement of histoplasmosis usually occurs in immune-compromised patients, patients with AIDS, or those...
BACKGROUND
Histoplasmosis is a systemic mycosis caused by (). Systemic involvement of histoplasmosis usually occurs in immune-compromised patients, patients with AIDS, or those taking immunosuppressive therapy. The present study aims to describe the clinical and laboratory characteristics and treatment outcome of histoplasmosis as the diagnosis is challenging and management protocol differs.
METHOD
This retrospective study was done using a data registry at the medicine department of Dhaka Medical College Hospital. Here, patients received the standard treatment of histoplasmosis. Here, patients received the standard treatment of histoplasmosis, and clinical outcome was assessed at 3 months following starting standard treatment.
RESULT
A total of nine patients were enrolled, six (66.7%) had systemic histoplasmosis. Three were poultry workers, and the most common comorbidity was diabetes 3 (33.3%). Fever 7 (77.7%), weight loss 6 (66.7%), hyperpigmentation 5 (55.5%), cough 4 (44.4%), oral ulceration 4 (44.4%), lymphadenopathy 4 (44.4%), and hypotension 3 (33.3%) were the most common clinical presentations. Seven (77.7%) out of nine patients were cured of histoplasmosis; however, one died before initiating antifungal medications and another one died due to a hypersensitivity reaction to liposomal amphotericin B. Conclusion: For local histoplasmosis, oral itraconazole is an effective antifungal medication. However, in disseminated Histoplasmosis, liposomal amphotericin B followed by oral itraconazole is still one of the preferable and effective treatment options. Clinicians should be aware of hypersensitivity reactions of liposomal amphotericin B and its management before giving an infusion.
PubMed: 38249268
DOI: 10.7759/cureus.50813 -
Journal of Fungi (Basel, Switzerland) Jul 2023In sub-Saharan Africa, an estimated 25% of people with HIV present with advanced HIV and are at high risk of opportunistic infections. Whereas histoplasmosis has...
In sub-Saharan Africa, an estimated 25% of people with HIV present with advanced HIV and are at high risk of opportunistic infections. Whereas histoplasmosis has occasionally been seen in Uganda, the understanding of the local risk of acute infection is limited. We sought to determine the prevalence of antigenuria using an enzyme immunoassay (EIA, clarus GM EIA, IMMY; Norman, OK, USA) in a cohort of outpatients with advanced HIV disease in Kampala, Uganda. Among the persons with positive urine antigen tests, we assessed their clinical presentation and outcomes. The EIA was run on stored urine samples as per the manufacturer's instructions. Specimens ≥1 EIA units were considered positive. Among the 388 tested urine samples, 4 (1.2%) were positive for antigen. The histoplasmosis prevalence among participants with a CD4 < 100 cells/mcL was 2.5% (4/158). Three of the four participants with a positive antigen test reported systemic symptoms consistent with histoplasmosis. All four participants had a positive urine lipoarabinomannan test and were treated for tuberculosis. By the four-week follow-up visit, all participants were clinically improved, alive, and in care without antifungal therapy. In advanced HIV, the clinical presentations of tuberculosis and histoplasmosis overlap. The value of histoplasmosis screening and pre-emptive treatment is an area of future research.
PubMed: 37504745
DOI: 10.3390/jof9070757 -
BioRxiv : the Preprint Server For... Jul 2023Targeted gene disruption is challenging in the dimorphic fungal pathogen due to the low frequency of homologous recombination. Transformed DNA is either integrated...
Targeted gene disruption is challenging in the dimorphic fungal pathogen due to the low frequency of homologous recombination. Transformed DNA is either integrated ectopically into the genome or maintained extra chromosomally by addition of telomeric sequences. Based on a system developed in , we adapted a CRISPR/Cas9 system to facilitate targeted gene disruption in with high efficiency. We express a codon-optimized version of Cas9 as well as guide RNAs from a single ectopic vector carrying a selectable marker. Once the desired mutation is verified, one can screen for isolates that have lost the Cas9 vector by simply removing the selective pressure. Multiple mutations can then be generated in the same strain by retransforming the Cas9 vector carrying different guides. We used this system to disrupt a number of target genes including and where loss-of-function mutations could be monitored visually by colony morphology or color, respectively. Interestingly, expression of two guide RNAs targeting the 5' and 3' ends of a gene allowed isolation of deletion mutants where the sequence between the guide RNAs was removed from the genome. Whole-genome sequencing showed that the frequency of off-target mutations associated with the Cas9 nuclease was negligible. Finally, we increased the frequency of gene disruption by using an endogenous regulatory sequence to drive guide RNA expression. These tools transform our ability to generate targeted mutations in .
PubMed: 37461713
DOI: 10.1101/2023.07.05.547774 -
The American Journal of Case Reports Jun 2024BACKGROUND Histoplasma capsulatum is prevalent in the mid-eastern United States and is an environmental fungus that causes human infection by the inhalation of its...
BACKGROUND Histoplasma capsulatum is prevalent in the mid-eastern United States and is an environmental fungus that causes human infection by the inhalation of its spores. It is commonly associated with areas containing large amounts of bird excrement and can survive for years in the soil. Only 1% of infected individuals develop disseminated histoplasmosis or Histoplasma endocarditis. CASE REPORT A 61-year-old man with atrial fibrillation had 8 months of fatigue, low-grade fevers, night sweats, and unexplained weight loss presented to the Emergency Department. He worked and lived in Central Florida and although he raised cattle, he denied exposure to birds or bats with regularity. A transesophageal echocardiogram confirmed a sessile echo density on the atrial surface of the mitral valve. His microbial Karius cell-free DNA test from his blood sample was positive for Histoplasma capsulatum, and he was immediately given intravenous liposomal amphotericin for 2 weeks. A tissue valve was used to successfully replace his mitral valve along with a coronary artery bypass and a maze procedure for his persistent atrial fibrillation and atrial flutter. The diagnosis of mitral valve endocarditis from disseminated histoplasmosis was confirmed by pathological analysis, and he was sent home on long-term itraconazole maintenance treatment. CONCLUSIONS Surgical intervention in combination with anti-fungal medication can be a lifesaving intervention for disseminated histoplasmosis. A thorough history is particularly important when evaluating a patient with an unknown infectious source, especially assessing for risk factors, including exposure to environmental factors, workplace, and animals.
Topics: Humans; Histoplasmosis; Male; Middle Aged; Mitral Valve; Endocarditis; Florida; Antifungal Agents; Echocardiography, Transesophageal; Heart Valve Diseases; Histoplasma
PubMed: 38863182
DOI: 10.12659/AJCR.943306 -
International Journal of Surgical... May 2024Histoplasmosis is commonly a self-limited fungal disease that primarily affects the lung and reticuloendothelial system. Cardiac involvement by histoplasmosis is...
Histoplasmosis is commonly a self-limited fungal disease that primarily affects the lung and reticuloendothelial system. Cardiac involvement by histoplasmosis is uncommon. In this report, we provide a detailed description of severe pulmonary histoplasmosis complicated by the disease involvement of the free wall of the right ventricle. A 55-year-old female presented with cough, fevers, dyspnea, and 30-pound unintentional weight loss in 6 months. Her past medical history was significant for supraventricular tachycardia with permanent pacemaker implantation. Imaging studies revealed an intracardiac mass accompanied by mediastinal lymphadenopathy and bilateral lung nodules. Endobronchial ultrasound-guided transbronchial needle aspiration of station 4R lymph nodes revealed numerous yeast forms, morphologically consistent with . The diagnosis was further corroborated by the elevated titers of serum antibodies against . The right ventricular mass debulking with biopsy showed necrotizing granulomatous inflammation involving nonvalvular endocardium and myocardium of the free wall of the right ventricle. The report documents an unusual presentation of pulmonary histoplasmosis accompanied by nonvalvular endocarditis and suggests a possible association between the site of the cardiac infection and the presence of a permanent intravascular pacer device.
Topics: Female; Humans; Middle Aged; Histoplasmosis; Histoplasma; Heart Ventricles; Lung; Endocarditis
PubMed: 37424325
DOI: 10.1177/10668969231185079 -
Microbiology Spectrum Apr 2024var (HCF) is a dimorphic fungus that causes epizootic lymphangitis in equids. Current diagnostic approaches, including culture, microscopy, and clinical presentation,...
UNLABELLED
var (HCF) is a dimorphic fungus that causes epizootic lymphangitis in equids. Current diagnostic approaches, including culture, microscopy, and clinical presentation, lack speed, sensitivity, and specificity when diagnosing clinical cases. In this study, equine blood and pus samples on Whatman FTA cards from Senegal ( = 3), The Gambia ( = 19), Ethiopia ( = 16), and Mali ( = 13) were tested using a real-time PCR (qPCR) protocol. The assay was optimized and tested for its suitability to detect and quantify HCF in blood and pus loaded onto Whatman FTA cards at sampling. Whatman FTA cards were tested for their suitability for use with qPCR and were found to recover DNA more efficiently than from direct extraction. Using TaqMan fluorescent probes and specific primers, the assay demonstrated 100% analytical specificity when detecting multiple strains of and no false positives with off-target organisms. The assay's diagnostic performance was measured against an existing nested internal transcribed spacer PCR protocol using a receiver operating characteristic curve. The test was found to have a diagnostic specificity and sensitivity of 100% and 71.4%, respectively, when analyzing pus samples using a cycle threshold (Ct) cutoff determined by Youden's index (27.75). Blood sample cutoff Ct value was proposed at 34.55. Further optimization is required to improve the performance of the protocol when applied to blood samples. This study has, for the first time, demonstrated the ability to detect and quantify the DNA of spp. in equine blood and pus samples with a high degree of accuracy, providing a platform to further investigate the pathogenesis and epidemiology of this disease.
IMPORTANCE
Histoplasmosis is a neglected yet major cause of morbidity and mortality in both equids and people in resource-scarce settings. One of the major hindrances to the control of histoplasmosis is a lack of readily available diagnostic tests. Tests are needed to support clinical decision-making and to be applied in population-based research to further understand this disease . This paper reports, for the first time, the validation and application of a qPCR to detect directly from equine clinical samples, bypassing the need to culture this notoriously difficult organism. We report and comment on the performance of the qPCR in comparison with our previously developed nested PCR.
Topics: Horses; Animals; Humans; Histoplasma; Histoplasmosis; Real-Time Polymerase Chain Reaction; Nucleic Acids; DNA, Fungal; Suppuration
PubMed: 38411051
DOI: 10.1128/spectrum.03100-23 -
Research Square Jul 2023Dimorphic fungi cause infection following inhalation of spores into the pulmonary system. In the lower respiratory tract, the conidia transform into the yeast phase...
INTRODUCTION
Dimorphic fungi cause infection following inhalation of spores into the pulmonary system. In the lower respiratory tract, the conidia transform into the yeast phase which are engulfed by alveolar macrophages and may be destroyed without disease manifestation. However, in some cases they may persist and cause fungal disease characterized by formation of granulomas in the infected tissues, which may mimic MTB.
OBJECTIVE
To explore if dimorphic fungi play any role in pulmonary disease among XpertTB/RIF Negative HIV Patients with chronic cough attending ISS Clinic at Mulago hospital Uganda.
METHODS
Sputum samples were collected from 175 consented HIV infected patients attending ISS Clinic. Upon Xpert/RIF test at ISS Clinic 21 of these tested positive, the 154 negative sputum samples were then subjected to PCR for dimorphic fungi at MBN Clinical Laboratories. Singleplex PCR using specific primers was used to detect a target sequency in the gene of each dimorphic fungi of interest, the resulting amplicons were electrophoresed on a 2% gel then visualized under UV light.
RESULTS
and were detected in 16.4% of the studied participants, with 9.1% and 7.1% respectively and 83.8% of the participant sample had no dimorphic fungi. Coccidiodes immitis, and were not detected in any of the participants.
CONCLUSION
Dimorphic fungi play a role in pulmonary disease among the HIV/AIDS with non- TB chronic in Uganda.
PubMed: 37546749
DOI: 10.21203/rs.3.rs-3194828/v1