Invasive Aspergillosis among Haematological Malignancy Patients in Ghana: A Pilot Study on Prevalence and Antifungal Prophylaxis at the National Referral Hospital.

BACKGROUND: Invasive aspergillosis (IA) among haematological malignancy patients is rarely diagnosed or studied in many African countries. Aspergillus galactomannan (GM) enzyme immunoassay (EIA) utilized in aiding diagnosis is not readily accessible in Ghana. Previous studies have evaluated the IMMY sona Aspergillus GM lateral flow assay (LFA) and suggested it as a potential alternative to the GM EIA. OBJECTIVES: We aimed to use the LFA in international (EORTC/ MSGERC) definitions to obtain preliminary data on IA among patients with haematological malignancies in Ghana with a focus on the prevalence and antifungal prophylaxis. METHODS: We conducted a pilot study among patients with haematological malignancies at the Korle-Bu Teaching Hospital, Ghana using the LFA, culture and computed tomography scan to screen for and classify IA cases according to international definitions. RESULTS: A total of 56 adult patients were recruited including acute leukaemia 14 (25.0%), chronic leukaemia 38 (67.9%), and lymphoma 4 (7.1%). Nine (16.1%) patients had a history of severe neutropenic episodes. All patients were on at least one chemotherapy drug. Three (5.4%) patients met the criteria for IA, comprising two probable IA in acute myeloid leukaemia and one possible IA in non-Hodgkin's lymphoma and constitutes one of five (20%) patients with ongoing severe neutropenia. The LFA was diagnostic in two IA patients. The IA cases were among 49 (87.5%) patients who did not receive antifungal prophylaxis. CONCLUSION: Proactive diagnostic approaches to IA and effective antifungal prophylaxis may be significant in the management of haematological malignancy patients with severe neutropenia in Ghana.

CONTEXTE: L'aspergillose invasive (AI) parmi les hémopathies malignes est rarement diagnostiquée ou étudiée dans de nombreux pays africains et le dosage immunoenzymatique (EIA) d'Aspergillus galactomannane (GM) utilisé pour faciliter le diagnostic n'est pas facilement accessible. Le test à flux latéral (TFL) IMMY sona® Aspergillus GM récemment introduit est évalué et suggéré comme alternative au GM EIA. OBJECTIFS: Nous avons cherché à utiliser les définitions TFA et les définitions internationales (EORTC/MSGERC) pour obtenir des données préliminaires sur l'AI dans les hémopathies malignes au Ghana en mettant l'accent sur la prévalence et la prophylaxie antifongique. MÉTHODES: Nous avons mené une étude pilote auprès de patients atteints d'hémopathie maligne à l'hôpital universitaire de Korle-Bu, au Ghana, en utilisant le TFL, la culture et la tomodensitométrie pour dépister et classer les cas d'AI selon les définitions internationales. RESULTATS: Au total, 56 patients adultes ont été recrutés, dont une leucémie aiguë (25 %), une leucémie chronique (67,9 %) et un lymphome (7,1 %), neuf (16,1 %) ayant des antécédents d'épisodes neutropéniques. La plupart des patients (70 %) avaient une maladie évolutive. Trois patients répondaient aux critères d'AI, comprenant deux AI probables et une AI possible, uniquement chez des patients atteints de leucémie aiguë et un sur cinq (20 %) avec une neutropénie en cours. Le TFL était utilisé comme méthode de diagnostique chez deux patients d'AI. Les cas d'AI concernaient tous les 49 (87,5 %) des patients n'ayant pas reçu de prophylaxie antifongique. CONCLUSION: L'AI a probablement une incidence de 5,4 % dans les leucémies, mais de 20 % chez les patients neutropéniques et chez aucun patient recevant une prophylaxie antifongique. Des approches diagnostiques proactives de l'AI et une prophylaxie antifongique efficace peuvent être importantes dans la prise en charge des hémopathies malignes au Ghana. Mots clés: Aspergillose invasive, Hémopathie maligne, Ghana, Aspergillus galactomannan, Neutropénie, Prophylaxie antifongique.

Diagnosing pulmonary aspergillosis is much easier than it used to be: a new diagnostic landscape.

Significant innovations in the past decade have resulted in more sensitive and faster diagnosis of allergic, chronic and invasive pulmonary aspergillosis, as well as Aspergillus bronchitis and Aspergillus nodules. This new diagnostic landscape has revealed that the incidence and prevalence of aspergillosis is substantially higher than previously understood, and is summarised in this review. Oral and intravenous antifungal treatment offers good clinical response rates for affected patients. Nevertheless, missed diagnoses mean that patients are over-treated with antibacterial agents, corticosteroids and anti-TB drugs, resulting in continuing illness and often death. The clinical introduction of several high performing diagnostic tests is helping to redefine patient management. It is well-known that Aspergillus antigen can be detected in 70-95% of bronchoscopy samples in patients with invasive and chronic aspergillosis in less than 1 hour. Aspergillus immunoglobulin G (IgG) (precipitins) is >90% sensitive and >85% specific for chronic and allergic aspergillosis. High-volume respiratory fungal culture and Aspergillus polymerase chain reaction have 3-5-fold higher sensitivity than routine bacterial culture. Aspergillus IgE (or skin prick testing) diagnoses Aspergillus sensitisation in asthma, cystic fibrosis, chronic obstructive pulmonary disease and post-TB, and correlates well with poorer lung function and/or exacerbations. Clinicians and laboratorians across the world need to mainstream these excellent new tools to improve clinical outcomes by delivering results in a more timely and accurate fashion.

Pulmonary TB and chronic pulmonary aspergillosis: clinical differences and similarities.

BACKGROUND: Pulmonary TB (PTB) and chronic pulmonary aspergillosis (CPA) are both progressive and debilitating parenchymal lung diseases with overlapping risk factors, symptomatology and radiological findings that often result in misdiagnosis of either disease.METHODS: We undertook a narrative review approach to describe the clinical and radiological manifestations of CPA and PTB and highlight the salient features that differentiate these two closely related maladies.RESULTS: CPA is a frequent complication of treated PTB. In fact, 15-90% of CPA cases occur in patients with residual lung lesions following treatment for PTB. While CPA predominantly affects older patients with underlying lung diseases, both PTB and CPA present with clinically indistinguishable symptoms. Chest imaging findings of cavitation and fibrosis are common to both diseases. However, lymphadenopathy, miliary pattern and pleural effusion are predictive of active PTB, while aspergilloma, pleural thickening and paracavitary fibrosis are more common in CPA. Aspergillus-specific IgG serology has a central role in differentiating PTB (both active and healed) from CPA with a high sensitivity and specificity.CONCLUSION: Aspergillus-specific IgG serology is key in differentiating PTB and PTB relapse from CPA. It may be worthwhile developing clinical predictive scores that can be used in low-income settings to differentiate active TB, post-TB disease and TB+CPA co-infection.

Estimates of serious fungal infection burden in Côte d'Ivoire and country health profile.

Due to limited access to more powerful diagnostic tools, there are few data on the burden of fungal infections in Côte d'Ivoire, despite a high HIV and TB burden and many cutaneous diseases. Here we estimate the burden of serious fungal infections in this sub-Saharan country with a health profiling description. National demographics were used and PubMed searches to retrieve all published articles on fungal infections in Côte d'Ivoire and other bordering countries in West Africa. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE (www.LIFE-Worldwide.org). The population of Côte d'Ivoire is around 25 million; 37% are children (≤14 years), and 9% are>65 years. Tinea capitis in children is common, measured at 13.9% in 2013. Considering the prevalence of HIV infection (2.6% of the population, a total of ∼500,000) and a hospital incidence of 12.7% of cryptococcosis, it is estimated that 4590 patients per year develop cryptococcosis. For pneumocystosis, it is suggested that 2640 new cases occur each year with the prevalence of 11% of newly diagnosed HIV adults, and 33% of children with HIV/AIDS. Disseminated histoplasmosis is estimated a 1.4% of advanced HIV disease - 513 cases. An estimated 6568 news cases of chronic pulmonary aspergillosis (CPA) occur after pulmonary tuberculosis (a 5-year prevalence of 6568 cases [26/100,000]). Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) were estimated in 104/100,000 and 151/100,000 respectively, in 1,152,178 adult asthmatics. Vulvovaginal candidiasis (VVC) is common and recurrent VVC affects ∼6% of women in their fertile years - 421,936 women. An unknown number develop candidaemia and invasive aspergillosis. The annual incidence of fungal keratitis is estimated at 3350. No cases of sporotrichosis, mucormycosis and chromoblastomycosis are described, although some cases of mycetoma and Conidiobolus infection have been reported. This study indicates that around to 7.25% (1.8 million) of the population is affected by a serious fungal infection, predominently tinea capitis in children and rVVC in women. These data should be used to inform epidemiological studies, diagnostic needs and therapeutic strategies in Côte d'Ivoire.

The Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala.

BACKGROUND: A Diagnostic Laboratory Hub (DLH) was set up in Guatemala to provide opportunistic infection (OI) diagnosis for people with HIV (PWH). METHODS: Patients newly presenting for HIV, PWH not receiving antiretrovirals (ARVs) for >90 days but returned to care (Return/Restart), and PWH on ARVs with symptoms of OIs (ARV treatment) were prospectively included. Screening for tuberculosis, nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcosis was done. Samples were couriered to the DLH, and results were transmitted electronically. Demographic, diagnostic results, disease burden, treatment, and follow-up to 180 days were analyzed. RESULTS: In 2017, 1953 patients were included, 923 new HIV infections (an estimated 44% of all new HIV infections in Guatemala), 701 on ARV treatment, and 315 Return/Restart. Three hundred seventeen (16.2%) had an OI: 35.9% tuberculosis, 31.2% histoplasmosis, 18.6% cryptococcosis, 4.4% NTM, and 9.8% coinfections. Histoplasmosis was the most frequent AIDS-defining illness; 51.2% of new patients had <200 CD4 cells/mm3 with a 29.4% OI incidence; 14.3% of OIs in new HIV infections occurred with CD4 counts of 200-350 cells/mm3. OIs were the main risk factor for premature death for new HIV infections. At 180 days, patients with OIs and advanced HIV had 73-fold greater risk of death than those without advanced disease who were OI-free. CONCLUSIONS: The DLH OI screening approach provides adequate diagnostic services and obtains relevant data. We propose a CD4 screening threshold of <350 cells/mm3. Mortality remains high, and improved interventions are required, including expansion of the DLH and access to antifungal drugs, especially liposomal amphotericin B and flucytosine.

High-volume culture and quantitative real-time PCR for the detection of Aspergillus in sputum.

OBJECTIVES: Sputum culture is an insensitive method for the diagnosis of pulmonary aspergillosis. Growth of the organism allows identification of the causative species and susceptibility testing, both of which can inform treatment choices. The current practice is to culture an aliquot of diluted sputum. We assessed the value of culturing large volumes of unprocessed sputum, a method that we have termed high-volume culture (HVC). METHODS: Specimens were processed by conventional culture (using an aliquot of homogenized, diluted sputum on Sabouraud agar at 37°C and 45°C for up to 5 days) and HVC (using undiluted sputum on Sabouraud agar at 30°C for up to 14 days). A separate specimen was tested by quantitative real-time PCR. Antifungal susceptibility testing was performed by the EUCAST standard. RESULTS: We obtained sputum specimens from 229 individuals with the following conditions: chronic pulmonary aspergillosis (66.8%, 153/229), allergic bronchopulmonary aspergillosis (25.3%, 58/229) and Aspergillus bronchitis (7.9%, 18/229). Individuals with invasive pulmonary aspergillosis were not included. The positivity rate of conventional culture was 15.7% (36/229, 95% CI 11.6%-21.0%) and that of HVC was 54.2% (124/229, 95% CI 47.7%-60.5%) (p < 0.001). The higher positivity rate of HVC was demonstrated regardless of administration of antifungal treatment. Quantitive real-time PCR had an overall positivity rate of 49.2% (65/132, 95% CI 40.9%-57.7%), comparable to that of HVC. CONCLUSION: Detection of Aspergillus spp. in sputum is greatly enhanced by HVC. HVC allows for detection of azole-resistant isolates that would have been missed by conventional culture. This method can be performed in any microbiology laboratory without the need for additional equipment.

Detection of Pneumocystis jirovecii by quantitative real-time PCR in oral rinses from Pneumocystis pneumonia asymptomatic human immunodeficiency virus patients.

Pneumocystis pneumonia (PCP) is a potentially life-threatening fungal infection usually seen in immunocompromised patients. Pneumocystis jirovecii can be easily detected from oral rinse samples in HIV patients with suspected PCP. In this study, a quantitative real-time PCR assay was used to establish the frequency of detection of P. jirovecii in oral rinses from HIV patients without respiratory symptoms or suspicion of PCP. Two saline oral rinses were collected from 100 ambulant HIV patients and from 60 COPD patients (comparator group). Four HIV patients were positive for P. jirovecii. In three patients, the first sample was positive and in one the second one was positive. One of these patients was on PCP prophylaxis and had a CD4+ count of 76 cells/mm3. The mean CD4+ count for all patients was 527 cells/mm3. All qRT-PCR test results for the COPD patients were negative. No patient developed PCP at six months follow-up. The qRT-PCR assay can be used to detect P. jirovecii DNA in oral rinse samples from HIV patients without evident clinical symptoms, however the oral carriage of this fungus was rare in our cohort of patients. In conclusion, although rare, a positive oral rinse P. jirovecii result may reflect colonisation, in particular in patients with HIV. This needs to be kept in mind when using oral rinses and qRT-PCR in the diagnosis of P. jirovecii infection.

Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.

Chronic pulmonary aspergillosis as a cause of smear-negative TB and/or TB treatment failure in Nigerians.

OBJECTIVE: To evaluate chronic pulmonary aspergillosis (CPA) as an alternative diagnosis of smear-negative tuberculosis (TB) and treatment failure in TB patients in Nigeria. METHODS: We conducted a cross-sectional multicentre survey in human immunodeficiency virus (HIV) positive and negative adult patients at the end of their TB treatment in clinics in Lagos and Ilorin states. All were assessed using clinical examination, chest X-ray (CXR) and aspergillus immunoglobulin G (IgG) serology, and some for sputum fungal culture. CPA was defined as a positive Aspergillus fumigatus IgG titre with compatible CXR or a positive sputum culture of Aspergillus with a visible fungal ball on CXR with symptoms of underlying lung disease. RESULTS: Of 208 patients recruited between June 2014 and May 2015, 153 (73.6%) were HIV-positive. The mean age was 39.8 years, 124 (59.6%) were female and 39 (18.8%) were unable to work. The median CD4 count was 169.5 cells/ml (range 4-593) in HIV-infected patients with positive Aspergillus IgG. Overall, 109 (52.4%) had documented TB, 140 (67.3%) had a productive cough and 50 had haemoptysis. CPA prevalence was 8.7%; 10 (6.5%) had HIV infection and 8 (14.5%) were HIV-negative (Fisher's exact P = 0.092). CONCLUSION: CPA is a neglected disease in Nigeria, and most cases match the World Health Organization diagnostic criteria for smear-negative TB.

Genetic susceptibility to severe asthma with fungal sensitization.

Severe asthma is problematic and its pathogenesis poorly understood. Fungal sensitization is common, and many patients with severe asthma with fungal sensitization (SAFS), used to denote this subgroup of asthma, respond to antifungal therapy. We have investigated 325 haplotype-tagging SNPs in 22 candidate genes previously associated with aspergillosis in patients with SAFS, with comparisons in atopic asthmatics and healthy control patients, of whom 47 SAFS, 279 healthy and 152 atopic asthmatic subjects were genotyped successfully. Significant associations with SAFS compared with atopic asthma included Toll-like receptor 3 (TLR3) (p = .009), TLR9 (p = .025), C-type lectin domain family seven member A (dectin-1) (p = .043), interleukin-10 (IL-10) (p = .0010), mannose-binding lectin (MBL2) (p = .007), CC-chemokine ligand 2 (CCL2) (2 SNPs, p = .025 and .041), CCL17 (p = .002), plasminogen (p = .049) and adenosine A2a receptor (p = .024). These associations differ from those found in ABPA in asthma, indicative of contrasting disease processes. Additional and broader genetic association studies in SAFS, combined with experimental work, are likely to contribute to our understanding of different phenotypes of problematic asthma.

Burden of serious fungal infections in Guatemala.

Guatemala is a developing country in Central America with a high burden of HIV and endemic fungal infections; we attempted to estimate the burden of serious fungal infections for the country. A full literature search was done to identify epidemiology papers reporting fungal infections from Guatemala. We used specific populations at risk and fungal infection frequencies in the population to estimate national rates. The population of Guatemala in 2013 was 15.4 million; 40% were younger than 15 and 6.2% older than 60. There are an estimated 53,000 adults with HIV infection, in 2015, most presenting late. The estimated cases of opportunistic fungal infections were: 705 cases of disseminated histoplasmosis, 408 cases of cryptococcal meningitis, 816 cases of Pneumocystis pneumonia, 16,695 cases of oral candidiasis, and 4,505 cases of esophageal candidiasis. In the general population, an estimated 5,568 adult asthmatics have allergic bronchopulmonary aspergillosis (ABPA) based on a 2.42% prevalence of asthma and a 2.5% ABPA proportion. Amongst 2,452 pulmonary tuberculosis patients, we estimated a prevalence of 495 for chronic pulmonary aspergillosis in this group, and 1,484 for all conditions. An estimated 232,357 cases of recurrent vulvovaginal candidiasis is likely. Overall, 1.7% of the population are affected by these conditions. The true fungal infection burden in Guatemala is unknown. Tools and training for improved diagnosis are needed. Additional research on prevalence is needed to employ public health measures towards treatment and improving the reported data of fungal diseases.

Serious fungal diseases in the Republic of Uzbekistan.

We have undertaken the first and preliminary estimation of severe and chronic mycotic diseases in the Republic of Uzbekistan, using a model proposed by LIFE (Leading International Fungal Education). Calculation was carried out based on data from 2014. Published results describing mycoses in Uzbekistan were identified. In the absence of published or official data, information about the frequency of mycoses from scientific literature elsewhere in groups at risk of development of fungal infections were taken into account. We also utilized methodology used in analogous estimations of mycoses in the Russian Federation. We estimate that of the 30.8 million population, 536,978 people (1.8% of the population) were affected by severe and chronic mycotic diseases. In 2014, there were 12,351 cases of acute invasive fungal diseases and 524,627 cases of chronic fungal diseases, including 1,941 cases of chronic pulmonary aspergillosis. The most frequent problems were recurrent vulvovaginal candidiasis (513,600 cases), trichophytosis of the scalp (6,414), and relapsed oral candidiasis (4,950). Results of the investigation indicate a significant prevalence of mycoses in the Republic of Uzbekistan.

[The burden of fungal infections in Algeria]. / Estimation des infections fongiques en Algérie.

In Algeria, superficial mycoses are very commonly diagnosed. Deep fungal infections are less often observed. Few data from Algeria are found in the literature. We report for the first time the main causes of these diseases in our country and provide burden estimates. We searched for existing data and estimated the incidence and prevalence of fungal diseases based on the population at risk and available epidemiological data. Demographic data were derived from the Service (Office) of the Statistics (ONES), World Health Organization (WHO), The Joint Nations Programme on HIV/AIDS (UNAIDS) and national published reports. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. Algeria has 40.4 million inhabitants and probably at least 568,900 (1.41 %) of Algerians have a serious fungal infection each year. Recurrent vulvovaginal candidiasis (485,000) and fungal asthma (72,000) are probably the commonest problems as there are over 1 million adult asthmatics. Candidaemia is estimated in 2020, invasive aspergillosis in 2865, intra-abdominal candidiasis in 303 people and are the most common life-threatening problems. AIDS is uncommon, but cancer is not (45,000 new cases of cancer among including 1500 in children) and nor is COPD (an estimated 317,762 patients of whom 20.3 % are admitted to hospital each year). A focus on improving the diagnosis and epidemiological data related to fungal infection is necessary in Algeria.

Burden of fungal infections in Algeria.

We report for the first time in Algeria and provide burden estimates. We searched for existing data and estimated the incidence and prevalence of fungal diseases based on the population at risk and available epidemiological data. Demographic data were derived from the National Office of Statistics (Office National des Statistiques: ONS), World Health Organization (WHO), The Joint Nations Programme on HIV/AIDS (UNAIDS) and national published reports. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. Algeria has 40.4 million inhabitants, and probably at least 568,900 (1.41%) of Algerians have a serious fungal infection each year. Recurrent vulvovaginal candidiasis (485,000) and fungal asthma (72,000) are probably the commonest problems, as there are over 1 million adult asthmatics. Candidaemia is estimated in 2,020 people, invasive aspergillosis in 2,865 people, and intra-abdominal candidiasis in 303 people; these are the most common life-threatening problems. AIDS is uncommon, but cancer is not (45,000 new cases of cancer including 1,500 in children), nor is COPD (an estimated 317,762 patients, of whom 20.3% are admitted to hospital each year). A focus on improving the diagnosis and epidemiological data related to fungal infection is necessary in Algeria.

Serious fungal infections in Chile.

The incidence and prevalence of fungal infections in Chile are unknown. Here, we have estimated the burden of serious fungal diseases from data obtained from clinical reports, WHO reports, Chilean census, OECD reports and comprehensive literature search available on PubMed and SciELO, among other scientific resources. Due the lack of official data about fungal diseases, frequencies were calculated based on the specific populations at risk. Recurrent vulvovaginal candidiasis (>4 episodes/year) is estimated to occur in 3108/100,000. Using a low international average rate of 5/100,000, we estimate 878 candidaemia cases and 132 patients with intra-abdominal candidiasis. Due to the low incidence of pulmonary tuberculosis (TB) in Chile, limited numbers of patients with chronic pulmonary aspergillosis are likely: a total of 1212, 25% following TB. Invasive aspergillosis is estimated to affect 296 patients following leukaemia therapy, transplantation and chronic obstructive pulmonary disease (COPD), 1.7/100,000. In addition, allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) were estimated to be around 97.9/100,000 and 127/100,000 respectively, in 675,772 adult asthmatics and 1700 CF patients. Given a 38,000 human immunodeficiency virus (HIV) population, with around 2189 new cases of acquired immune deficiency syndrome (AIDS) annually, cryptococcal meningitis and Pneumocystis pneumonia are estimated at 0.12/100,000 and 4.3/100,000, respectively. In total, 325,000 (1.9%) people in Chile develop serious fungal infections annually. Respiratory fungal disease predominates in Chile; a national action plan for fungal disease is urgently needed, including epidemiological studies to validate the estimates.

Serious fungal infections in Egypt.

We aimed to estimate the burden of serious fungal infections in Egypt, currently unknown, based on the size of the populations at risk and available epidemiological data. Data were obtained from the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS), and published reports with clearcut denominators. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. The population of Egypt in 2011 was ∼82,500,000; 31% children, and 8% women >60 years of age. Amongst about 21.8 million women aged 15-50 years, recurrent vulvovaginal candidiasis (≥4 episodes/year) is estimated to occur in 1.3 million (3,169/100,000 females). Using a low international average rate of 5/100,000, we estimate 4,127 cases of candidaemia, and 619 patients with intra-abdominal candidiasis. Amongst the survivors of pulmonary tuberculosis (TB) in Egypt in 2012, 319 new cases of chronic pulmonary aspergillosis (CPA) are likely, a prevalence of 1,005 post-TB and a total prevalence estimate of 3,015 CPA patients in all. Asthma is common in Egypt, affecting 9.4% of adults, 5.35 million, and so ABPA and SAFS were estimated in around 162/100,000 and 214/100,000 respectively. Invasive aspergillosis is estimated to affect 495 patients following leukaemia therapy, there are an estimated 37 cases in renal and liver transplant recipients, and an estimated 132 patients develop IA in the context of lung cancer. Amongst 641,000 COPD admissions to hospital each year, 8,337 patients develop IA. The total HIV-infected population is small, with an estimated 6,500 patients, 2,500 not on antiretroviral therapy. Amongst HIV-infected patients, 38 (0.6%) cases of cryptococcal meningitis and 125 (1.9%) cases of Pneumocystis pneumonia are estimated each year. Fungal keratitis is common, with 28-55% (mean 40%) of corneal infections being fungal, an estimated total of 11,550 cases. The present study indicates that 2% of the Egyptian population is affected by fungal infections. The estimates are certainly incomplete, and need further epidemiological and diagnostic studies.

Serious fungal infections in Ecuador.

There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (<200 CD4 cell counts) is ∼10,000, with a rate of 11.1% (1100) of histoplasma, 7% (700) of cryptococcal meningitis, and 11% (1070) of Pneumocystis pneumonia. The burden of candidemia is 1037. Recurrent Candida vaginitis (≥4 episodes per year) affects 307,593 women aged 15-50 years. Chronic pulmonary aspergillosis probably affects ∼476 patients following tuberculosis (TB). Invasive aspergillosis is estimated to affect 748 patients (∼5.5/100,000). In addition, allergic bronchopulmonary aspergillosis (ABPA) in asthma and severe asthma with fungal sensitization (SAFS) were estimated to affect 26,642 and 45,013 people, respectively. Our estimates indicate that 433,856 (3%) of the population in Ecuador is affected by serious fungal infection.

Serious fungal infections in Korea.

Information on the incidence and prevalence of fungal infections is of critical value in public health policy. However, nationwide epidemiological data on fungal infections are scarce, due to a lack of surveillance and funding. The objective of this study was to estimate the disease burden of fungal infections in the Republic of Korea. An actuarial approach using a deterministic model was used for the estimation. Data on the number of populations at risk and the frequencies of fungal infections in those populations were obtained from national statistics reports and epidemiology papers. Approximately 1 million people were estimated to be affected by fungal infections every year. The burdens of candidemia (4.12 per 100,000), cryptococcal meningitis (0.09 per 100,000), and Pneumocystis pneumonia (0.51 per 100,000) in South Korea were estimated to be comparable to those in other countries. The prevalence of chronic pulmonary aspergillosis (22.4 per 100,000) was markedly high, probably due to the high burden of tuberculosis in Korea. The low burdens of allergic bronchopulmonary aspergillosis (56.9 per 100,000) and severe asthma with fungal sensitization (75.1 per 100,000) warrant further study. Oral candidiasis (539 per 100,000) was estimated to affect a much larger population than noted in previous studies. Our work provides valuable insight on the epidemiology of fungal infections; however, additional studies are needed.