Chronic Pulmonary Aspergillosis after Surgical Treatment for Non-Small Cell Lung Cancer-An Analysis of Risk Factors and Clinical Outcomes.

Chronic pulmonary aspergillosis (CPA) is a rare but significant complication of lung cancer surgery. Its effect on survival remains unclear. Our aim was to describe the outcomes of the patients who developed CPA following the surgery for non-small cell lung cancer (NSCLC), identify the risk factors associated with its development following lung resection, and evaluate its impact on survival. All the patients with a diagnosis of CPA and operated NSCLC were identified in the National Aspergillosis Centre (NAC) database (2009-2020). Additional patients were identified in the Northwest Clinical Outcomes Research Registry (2012-2019) database. A regression analysis was performed to examine potential links between CPA and long-term outcomes and also to identify the factors associated with the development of CPA. The primary outcomes were the development of CPA, 1-year and 5-year mortality, and overall survival. Thirty-two patients diagnosed with CPA after lung resection were identified in the NAC database, of which 11 were also contained within the NCORR database, with a prevalence of 0.2% (n = 11/4425). Post-operative CPA was associated with significantly lower survival on log-rank analysis (p = 0.020). Mortality at one year was 25.0% (n = 8) and 59.4% (n = 19) at five years after the CPA diagnosis. On univariable analysis, a lower mean percentage-predicted forced expiratory volume in 1 s, ischaemic heart disease, and chronic obstructive pulmonary disease were all significantly associated with CPA development. CPA is a rare complication following lung cancer surgery which has a significant impact on long-term survival. Its development may be associated with pre-existing cardiopulmonary comorbidities. Further research in larger cohorts is required to substantiate these findings.

Aspergillus nodules: Natural history and the effect of antifungals.

BACKGROUND: Aspergillus nodules are classified as a subset of chronic pulmonary aspergillosis. The optimal management approach is not known as their natural evolution following biopsy, the rate of progression to chronic cavitary pulmonary aspergillosis (CCPA) and the effect of antifungal treatment have not been described. OBJECTIVES: To describe the clinical course of patients diagnosed with Aspergillus nodules and the effect of antifungal treatment. PATIENTS/METHODS: We present a series of 23 patients with histologically confirmed Aspergillus nodules and describe serial imaging, antifungal treatment and progression to other diagnoses. RESULTS: Thirteen patients were diagnosed after a CT-guided biopsy and 10 after surgical resection. Among those who had CT-guided biopsy, 8 did not receive antifungal treatment; the nodule was stable or smaller in all cases on subsequent CT scan after a mean of 15.5 months. However, one patient developed squamous cell carcinoma after 16 months and another developed CCPA after 7 months. Among the 5 patients who received antifungals for at least 4 weeks, the nodule was smaller in 1 and stable in 4. One patient developed CCPA 3 years after the biopsy. No patient who had a surgical resection subsequently had a CCPA diagnosis. CONCLUSION: Most Aspergillus nodules remained stable or improved following biopsy, irrespective of the effect of antifungals. However, CCPA can develop occasionally in patients with Aspergillus nodules and ongoing radiological follow-up may be warranted when the nodule is not resected.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

A diverse spectrum of mycoses histologically diagnosed in Ghana: Insights from a 10-year retrospective study.

In Ghana, most laboratory diagnoses of severe mycoses are based on histopathology findings due to inadequate availability of serology, culture, and molecular tests. The aim of this study was to evaluate the spectrum of mycoses diagnosed in Ghana. We retrospectively reviewed reports from 2012 to 2021 from three major pathology laboratories in Ghana to identify reports indicating the presence of fungal elements and diagnosis of a mycosis, then extracted demographic, clinical history, site of infection, stain(s), used and diagnosed mycosis details. Over the 10-year period, 107 cases were found. No apparent increasing and decreasing trend in the number of cases per year or in a period was observed. The age range of affected patients was from 4 to 86 years. Special stains for fungi were only used in 22 of 107 (20.6%) of cases. The most frequently affected site was the sino-nasal area (34%). Mycosis type was determined for 58 (54.2%) cases, comprising aspergillosis (21), candidiasis (14), dermatophytosis (6), mucormycosis (3), two cases each of chromoblastomycosis, histoplasmosis, eumycetoma, entomophthoromycosis, sporotrichosis, and Malassezia infection and a single case each of cryptococcosis and deep onychomycosis. Of the 53 (49.5%) cases with presumptive diagnosis data, only seven (13.2%) had a pre-biopsy suspicion of mycosis. There is a wide spectrum of mycoses in Ghana, including endemic mycoses not previously reported. Improving the use of special fungal stains could increase yield and mycoses identification. Laboratory diagnostic capacity needs enhancement to complement histopathology investigations with serology, culture, and molecular methods.

In Ghana, diagnosis of mycoses is mainly based on histopathology findings. To appreciate the varied mycoses diagnosed, we reviewed the reports of major laboratories from 2012 to 2021 and found 107 cases including endemic, rare, and previously unreported cases with fungal stains unusually used.

Chronic Pulmonary Aspergillosis: Clinical Presentation and Management.

Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of Aspergillus organisms in the lungs of patients with chronic lung disease. CPA is more common than was realized two decades ago. Recognition remains poor, despite recent studies from many countries highlighting the high prevalence in at-risk populations. In low- and middle-income countries, CPA may be misdiagnosed and treated as tuberculosis (TB). In addition, CPA may develop following successful TB treatment. The coronavirus disease pandemic has resulted in significant disruption to provision of TB care, likely leading to more extensive lung damage, which could increase the risk for CPA.Although CPA refers to various syndromes, the classic presentation is that of chronic cavitary pulmonary aspergillosis, which manifests as one or more progressive cavities with or without a fungal ball, accompanied by systemic and respiratory symptoms for at least 3 months. Diagnosis relies on Aspergillus immunoglobulin G in serum, as sputum culture lacks sensitivity. Differential diagnosis includes mycobacterial infection, bacterial lung abscess or necrotizing pneumonia, lung cancer, and endemic fungi.The aim of antifungal treatment in CPA is to improve symptoms and quality of life, and to halt progression, and possibly reverse radiological changes. Current recommendations suggest treatment for 6 months, although in practice many patients remain on long-term treatment. Improvement may manifest as weight gain and improvement of symptoms such as productive cough, hemoptysis, and fatigue. Surgical management should be considered in cases of diagnostic uncertainty, in significant hemoptysis, and when there is concern for lack of response to therapy. Itraconazole and voriconazole are the first-line azoles, with more experience now accumulating with posaconazole and isavuconazole. Side effects are frequent and careful monitoring including therapeutic drug monitoring is essential. Intravenous antifungals such as echinocandins and amphotericin B are used in cases of azole intolerance or resistance, which often develop on treatment. Relapse is seen after completion of antifungal therapy in around 20% of cases, mostly in bilateral, high-burden disease.Several research priorities have been identified, including characterization of immune defects and genetic variants linked to CPA, pathogenetic mechanisms of Aspergillus adaptation in the lung environment, the contribution of non-fumigatus Aspergillus species, and the role of new antifungal agents, immunotherapy, and combination therapy.

Prevalence and clinical implications of respiratory viruses in asthma during stable disease state and acute attacks: Protocol for a meta-analysis.

INTRODUCTION: Viruses are detected in over 50% of acute asthma attacks and in a notable proportion of patients with asthma during stable disease state They are associated with worse outcomes. We will conduct a series of systematic reviews and meta-analyses to quantify the prevalence and clinical burden of various respiratory viruses in stable asthma and acute asthma attacks. In addition, we will assess the viral loads of respiratory viruses during stable and acute asthma, to explore whether viral load could differentiate attacks triggered by viruses versus those where viruses are present as "innocent bystanders". MATERIALS AND METHODS: Based on a prospectively registered protocol (PROSPERO, ID: CRD42023375108) and following standard methodology recommended by Cochrane, we will systematically search Medline/PubMed, EMBASE, the Cochrane Library and relevant conference proceedings for studies assessing the prevalence or clinical burden of respiratory viruses in asthma. Methodological rigour of the included studies will be appraised using a tool specific for prevalence studies and the Newcastle-Ottawa Scale respectively. In anticipation of significant clinical and methodological heterogeneity, we will conduct random effect meta-analyses. For evaluating the prevalence of viruses, we will perform meta-analyses of proportions using the inverse variance method, and the Freeman-Tukey transformation. We will conduct meta-regression analyses for exploring heterogeneity. CONCLUSION: We envisage that these systematic reviews and meta-analyses will quantify the prevalence and burden of respiratory viruses in stable and acute asthma and will drive future research and clinical practice.

Predictive factors for treatment response and mortality in chronic pulmonary aspergillosis.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is associated with significant mortality, and suboptimal antifungal treatment response. We describe predictive factors for treatment response and survival. METHODS: We retrospectively analysed clinical, serological and radiological parameters at baseline and following antifungal treatment in patients with CPA and correlated with clinical and radiological response and survival. RESULTS: Fifty-nine patients were included with a mean age of 61 years. Thirty (51%) had a diagnosis of COPD. On clinical assessment at 6 months, 21 (36%) had clinically improved, 20 (34%) were clinically stable and 15 (25%) had deteriorated. Radiological improvement was observed in 30 (53%), stability in 11 (19%) and deterioration in 16 (28%). Only a lower C-reactive protein (CRP) at baseline was associated with a favourable clinical-radiological response. On univariate analysis, lower CRP, higher albumin, lower Aspergillus IgG and use of inhaled steroids were associated with lower mortality. An overall favourable response at 6 months was associated with lower mortality. CONCLUSION: Inflammatory markers and Aspergillus IgG were predictors of mortality in CPA. This suggests that mortality in CPA is driven mainly by the chronic fungal infection itself rather than the underlying disease, therefore early optimised treatment of CPA may lead to improved outcomes.

Aspergillus sensitisation detection using point-of-care lateral flow assay in moderate to severe asthma.

Allergic fungal airway diseases are associated with asthma exacerbations and poor control. However, the early identification of allergic Aspergillus airway diseases can be challenging, especially in resource-poor countries. We aimed to evaluate the clinical utility of the point-of-care Aspergillus IgG-IgM lateral flow assay in diagnosing Aspergillus airway diseases in patients with moderate-severe asthma. Patients with moderate-severe asthma, severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) were recruited. Clinical information was extracted from clinical records. Blood samples were collected for serological tests. Serum samples were evaluated using Aspergillus immunochromatographic test (ICT). A total of 65 patients were recruited into the study, of whom 23.1% had clinical diagnosis of ABPA, 18.5% had SAFS and 58.5% had moderate-to-severe asthma who did not fit ABPA or SAFS criteria. The ICT test gave a sensitivity of 69 [95% confidence interval: 51-88]% and a specificity of 77 [60-88]% in predicting a positive Aspergillus IgG test. The sensitivity and specificity for a positive Aspergillus IgE were 77 [59-88]% and 86 [71-94]%, respectively. The majority (sensitivity: 87 [62-96]%) of patients with ABPA had positive ICT results, with a specificity of 70%. The negative predictive value was high (95 [82-99]%) with a low negative likelihood ratio (< 0.2), making it potentially useful in ruling out ABPA. The ICT assay may be valuable in ruling out ABPA in resource-limited countries where serological investigations are less feasible. The ICT assay may be particularly useful in ruling out ABPA and warrants further validation.

Allergic Aspergillus diseases can make patients with asthma more unwell, but this is difficult to diagnose, especially in developing countries where tests are not widely available. We have found that a cheap, easy-to-use and fast test may be useful in diagnosing allergic Aspergillus diseases.

The Fungal and Bacterial Interface in the Respiratory Mycobiome with a Focus on Aspergillus spp.

The heterogeneity of the lung microbiome and its alteration are prevalently seen among chronic lung diseases patients. However, studies to date have primarily focused on the bacterial microbiome in the lung rather than fungal composition, which might play an essential role in the mechanisms of several chronic lung diseases. It is now well established that Aspergillus spp. colonies may induce various unfavorable inflammatory responses. Furthermore, bacterial microbiomes such as Pseudomonas aeruginosa provide several mechanisms that inhibit or stimulate Aspergillus spp. life cycles. In this review, we highlighted fungal and bacterial microbiome interactions in the respiratory tract, with a focus on Aspergillus spp.

Update on the treatment of chronic pulmonary aspergillosis.

PURPOSE OF REVIEW: Chronic pulmonary aspergillosis is a major global infection in individuals with preexisting structural lung diseases and those with immunodeficiencies, in particular cytokine defects. Current treatment options are confined to just three drug classes, the triazoles, the echinocandins and amphotericin B. However, antifungal resistance is rapidly emerging for the triazoles, the only available oral therapy for this chronic condition. RECENT FINDINGS: Fortunately, there are now a number of novel antifungals in the development pipeline, mostly now in Phase 3 studies, with a potential for the treatment of chronic pulmonary aspergillosis. However, almost all current randomized triazoles of novel antifungals are primarily undertaken in patients with invasive candidiasis or invasive mould infections. Given the poor outcomes from treatment with antifungals in chronic pulmonary aspergillosis, in part associated with triazole resistance, we urgently need clinical trials of novel agents either as monotherapy or in combination for this disease. In addition, there is an emerging understanding of the role of immunotherapies for the treatment of chronic pulmonary aspergillosis, especially in the context of cytokine defects. Therefore, better understanding of the role of adjunctive immunotherapies such as interferon-gamma is also required. SUMMARY: In this review, we give an overview of current management of chronic pulmonary aspergillosis, and novel antifungals and immunotherapies for the future.

The clinical spectrum of aspergillosis in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. In this review, we present the clinical spectrum and pathogenesis of syndromes caused by Aspergillus in COPD namely invasive aspergillosis (IA), community-acquired Aspergillus pneumonia, chronic pulmonary Aspergillosis and Aspergillus sensitisation. Some of these entities are clearly linked to COPD, while others may coexist, but are less clearly liked directly to COPD. We discuss current uncertainties as these pertain to IA in COPD cohorts and explore areas for future research in this field.

EQUAL CPA Score 2022: a tool to measure guideline adherence for chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) can complicate underlying pulmonary diseases, and clinical management of CPA is challenging. Guidelines support clinicians but due to the complexity of the disease they can be difficult to adhere to. OBJECTIVES: To map current guideline recommendations for the clinical management of CPA into a scoring tool to facilitate and quantify guideline adherence in clinical practice. METHODS: Recommendations for diagnosis, treatment and follow-up of CPA presented in the current ESCMID/ERS/ECMM and CPAnet guidance documents were assembled and weighed on the basis of their strength of recommendation and level of evidence. RESULTS: Twenty-seven recommendations were identified, resulting in a total maximum EQUAL CPA Score of 51. For diagnostics (ScoreMax = 27), a strong emphasis on expert consultation, culture, direct microscopy, histopathology, serology and imaging was reflected in respective points, whereas molecular techniques and susceptibility testing count into the diagnostics score to a lesser extent.Ten treatment recommendations (ScoreMax = 14), including antifungal therapy, therapeutic drug monitoring and treatment duration, were identified. Surgery, where indicated, adds three points. For refractory disease or intolerance of first-line antifungal treatment, optimal second-line treatment added another two points.During follow-up (ScoreMax = 10), response assessment via imaging gave three points, while culture and serology added two points each to the ScoreMax. CONCLUSION: The EQUAL CPA Score intents to be used as a comprehensive tool for measuring guideline adherence. If adherence to current guidelines is associated with clinical outcome, this will be assessed in future studies.

Chronic pulmonary aspergillosis is common among patients with presumed tuberculosis relapse in Ghana.

Chronic pulmonary aspergillosis (CPA) may mimic pulmonary tuberculosis (PTB). The two diseases are clinically indistinguishable and may result in CPA misdiagnosed as PTB or vice versa. Although PTB is largely recognised as a differential diagnosis of CPA and often ruled out prior to CPA diagnosis, the reverse is uncommon. The aim of this study was to determine the proportion of CPA cases among patients being assessed for PTB. A cross-sectional survey was conducted among consecutive patients referred for GeneXpert Mycobacterium tuberculosis test for the diagnosis of PTB at the Korle-Bu Teaching Hospital, Accra, Ghana. Patients' demographics, clinical and socioeconomic details were obtained using a structured questionnaire. Blood was collected for Aspergillus and HIV serology, and sputum samples obtained for Aspergillus culture. Chest radiograph was obtained, and computed tomography scan was also done for patients with positive Aspergillus serology or cavitation. CPA was defined using an algorithm developed by the Global Action for Fungal Infections (GAFFI) international expert panel. A total of 154 patients were included in the analysis, of whom 134 (87%) did not have a prior PTB diagnosis. There were 41 (26.6%) GeneXpert positive cases. CPA prevalence was 9.7% overall, but 50% in patients with a prior history of PTB and 3.7% in those without previous PTB. Although CPA is rarely considered as a differential diagnosis of PTB in Ghana, our findings show that CPA may affect half of patients being assessed for PTB relapse. Efforts to diagnose CPA should be prioritised in this patient group.

Chronic pulmonary aspergillosis (CPA) may be misdiagnosed as pulmonary tuberculosis (PTB), or vice versa due to clinical similarities. Screening for CPA among patients undergoing investigation for relapsed PTB and new PTB revealed that half and about four in 100 patients, respectively, had CPA.

Special Issue: Chronic Pulmonary Aspergillosis.

I would like to thank all authors who contributed to this Journal of Fungi Special Issue on Chronic Pulmonary Aspergillosis (CPA) [...].

Cryptococcal and Histoplasma Antigen Screening Among People With Human Immunodeficiency Virus in Ghana and Comparative Analysis of OIDx Histoplasma Lateral Flow Assay and IMMY Histoplasma Enzyme Immunoassay.

Background: Cryptococcal meningitis (CM) and disseminated histoplasmosis (DH) are common in people with human immunodeficiency virus (PWH) and diagnosed by detecting cryptococcal antigen (CrAg) and Histoplasma antigen (HistoAg), respectively. In Ghana, CM and DH are rarely suspected by clinicians due to limited epidemiological data. Methods: This study was conducted among PWH in Ghana who are unwell. Sociodemographic and clinical data were collected by questionnaire. Serum and/or urine were screened for CrAg and HistoAg, using IMMY CrAg lateral flow assay (LFA) and IMMY Histoplasma enzyme immunoassay (EIA) kits, respectively, regardless of symptoms. Samples run with IMMY Histoplasma EIA were simultaneously run with Optimum Imaging Diagnostics (OIDx) Histoplasma LFA. Laboratory investigations were conducted by the research team, and diagnosis incorporating clinical assessment, screening, and confirmatory testing results and treatment decisions were made by the clinical team. Treatment and outcome information on CM and DH patients were evaluated. Results: Overall, 150 participants were recruited. There were 73% (n = 109) females, and the age range was 18-62 years. The prevalence rates of CrAg and HistoAg were 2.7% (4 of 150) and 4.7% (5 of 107), respectively. The OIDx Histoplasma LFA showed a high concordance (98.4%) with the IMMY Histoplasma EIA. All antigen-positive cases by standard tests were diagnosed with CM and DH. Antifungal treatment was given in 5 patients and follow-up revealed 2 deaths and 3 recoveries. Conclusions: Histoplasmosis among PWH may be more common than previously anticipated and may be more frequent than cryptococcosis in Ghana. The performance of the OIDx Histoplasma LFA should be further explored.

Triazole resistance in Aspergillus fumigatus isolates in Africa: a systematic review.

Emergence of triazole resistance has been observed in Aspergillus fumigatus over the past decade including Africa. This review summarizes the current published data on the epidemiology and reported mechanisms of triazole-resistant Aspergillus fumigatus (TRAF) in both environmental and clinical isolates from Africa. Searches on databases Medline, PubMed, HINARI, Science Direct, Scopus and Google Scholar on triazole resistance published between 2000 and 2021 from Africa were performed. Isolate source, antifungal susceptibility using internationally recognized methods, cyp51A mechanism of resistance and genotype were collected. Eleven published African studies were found that fitted the search criteria; these were subsequently analyzed. In total this constituted of 1686 environmental and 46 clinical samples. A TRAF prevalence of 17.1% (66/387) and 1.3% (5/387) was found in respectively environmental and clinical settings in African studies. Resistant to itraconazole, voriconazole, and posaconazole was documented. Most of the triazole-resistant isolates (30/71, 42.25%) were found to possess the TR34/L98H mutation in the cyp51A-gene; fewer with TR46/Y121F/T289A (n = 8), F46Y/M172V/E427K (n = 1), G54E (n = 13), and M172V (n = 1) mutations. African isolates with the TR34/L98H, TR46/Y121F/T289A and the G54E mutations were closely related and could be grouped in one of two clusters (cluster-B), whereas the cyp51A-M172V mutation clustered with most cyp51A-WT strains (cluster-A). A single case from Kenya shows that TR34/L98H from environmental and clinical isolates are closely related. Our findings highlight that triazole resistance in environmental and clinical A. fumigatus is a cause for concern in a number of African countries. There is need for epidemiological surveillance to determine the true burden of the problem in Africa. LAY SUMMARY: Emergence of triazole resistance has been observed in Aspergillus fumigatus. TRAF was found from environmental (17.1%) and clinical (1.3%) settings in Africa. We highlighted that triazole resistance in environmental and clinical A. fumigatus is a cause for concern in a number of African countries.

Unravelling the Molecular Identification and Antifungal Susceptibility Profiles of Aspergillus spp. Isolated from Chronic Pulmonary Aspergillosis Patients in Jakarta, Indonesia: The Emergence of Cryptic Species.

Cryptic species of Aspergillus have rapidly increased in the last few decades. Chronic pulmonary aspergillosis (CPA) is a debilitating fungal infection frequently affecting patients with previous TB. The identification and antifungal susceptibility profiles of different species of Aspergillus are important to support the management of CPA. The aim of this study was to describe the molecular and susceptibility profiles of Aspergillus isolated from CPA patients. The species identity of isolates was determined by combined DNA analyses of internal transcribed space (ITS), partial ß-tubulin genes, and part of the calmodulin gene. We revealed a high (27%) prevalence of cryptic species among previous tuberculosis patients with persistent symptoms. Twenty-nine (49%) patients met the criteria for diagnosis of CPA with 24% containing Aspergillus cryptic species. This is the first report of five cryptic Aspergillus species from clinical isolates in Indonesia: A. aculea tus, A. neoniger, A. brunneoviolacues, A. welwitschiae, and A. tubingensis. Significantly, there was decreased sensitivity against itraconazole in the CPA group (66% susceptible to itraconazole) compared to the non-CPA group (90% susceptible to itraconazole) (p = 0.003). The species-level characterisation of Aspergillus and its antifungal susceptibility tests demands greater attention to better the management of CPA patients.

Histoplasmosis in Africa: Current perspectives, knowledge gaps, and research priorities.

BACKGROUND: Histoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum (Hcc) and Histoplasma capsulatum var. duboisii (Hcd) causes infection in humans and commonly termed classical or American histoplasmosis and African histoplasmosis, respectively. Histoplasma capsulatum var. farciminosum (Hcf) affects equines. In recent times, there have been heightened sensitization on fungal infections such as histoplasmosis in Africa, aimed at improving awareness among relevant stakeholders, particularly healthcare workers. This effort is expected to be paralleled with increased detection of both classical and African histoplasmosis, which has remained underdiagnosed over the years. In this narrative review, we describe the current perspectives of histoplasmosis in Africa, identify knowledge gaps, and suggest research priorities. METHODS: A PubMed, Google Scholar, and Africa Journal Online (AJOL) literature search was conducted for studies on histoplasmosis in Africa between 2000 and 2020. Histoplasmosis essays in medical mycology textbooks were also consulted. This narrative review was prepared from the data gathered. FINDINGS: In the past 2 decades, histoplasmosis in general has seen a relative increase in case detection in some Africa countries, probably attributable to the gradually increasing medical mycology advocacy efforts in Africa. Histoplasmosis cases are dominated by African histoplasmosis mostly in Western and Central Africa, while classical histoplasmosis is more common in Southern and Northern Africa. Although both classical and African histoplasmosis are common in Africa, the latter is more restricted to Africa, and cases outside the continent usually have a travel history to the continent. Despite the clinical and laboratory difference between African histoplasmosis and classical histoplasmosis, it is not straightforward to distinguish them. The typical manifestation of African histoplasmosis is the appearance of lesions affecting the skin, bones, and lymph nodes and unusually linked to human immunodeficiency virus (HIV)/AIDS. By contrast, classical histoplasmosis mostly affects the lungs and is often associated with immunosuppression, mainly HIV/AIDS. The present perspectives of histoplasmosis in Africa highlight unclear details on the true burden, strain diversity, infection route and genetic basis of African histoplasmosis, availability of specie-specific diagnostic tools, and compliance with recommended antifungal therapy. These knowledge gaps represent research questions that require scientific exploration. CONCLUSIONS: Despite a subtle increase in identifying histoplasmosis cases in Africa, it remains underdiagnosed and neglected in some parts of the continent. Increasing awareness and training among healthcare workers, bridging diagnostic and therapeutic gaps, and encouraging more research in Africa are crucial to improve the current perspectives of histoplasmosis in Africa.