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.

Maturation of adenovirus primes the protein nano-shell for successful endosomal escape.

The ability of adenoviruses to infect a broad range of species has spurred a growing interest in nanomedicine to use adenovirus as a cargo delivery vehicle. While successful maturation of adenovirus and controlled disassembly are critical for efficient infection, the underlying mechanisms regulating these processes are not well understood. Here, we present Atomic Force Microscopy nanoindentation and fatigue studies of adenovirus capsids at different maturation stages to scrutinize their dynamic uncoating properties. Surprisingly, we find that the early intermediate immature (lacking DNA) capsid is mechanically indistinguishable in both break force and spring constant from the mature (containing DNA) capsid. However, mature and immature capsids do display distinct disassembly pathways, as revealed by our mechanically-induced fatigue analysis. The mature capsid first loses the pentons, followed by either long-term capsid stability or abrupt and complete disassembly. However, the immature capsid has a stable penton region and undergoes a stochastic disassembly mechanism, thought to be due to the absence of genomic pressure. Strikingly, the addition of the genome alone is not sufficient to achieve penton destabilization as indicated by the penton stability of the maturation-intermediate mutant, G33A. Full penton destabilization was achieved only when the genome was present in addition to the successful maturation-linked proteolytic cleavage of preprotein VI. Therefore these findings strongly indicate that maturation of adenovirus in concert with genomic pressure induces penton destabilization and thus, primes the capsid for controlled disassembly. This latter aspect is critical for efficient infection and successful cargo delivery.

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.

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.

[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.

Serious fungal infections in the Philippines.

The Philippines is a low middle-income, tropical country in Southeast Asia. Infectious diseases remain the main causes of morbidity, including tuberculosis. AIDS/HIV prevalence is still low at <1%, but is rapidly increasing. Fungal disease surveillance has not been done, and its burden has never been estimated. This becomes more important as the population of immunocompromised patients increases, drawn from patients with AIDS, TB, malignancies, and autoimmune diseases requiring chronic steroid use. Using the methodology of the LIFE program ( www.LIFE-worldwide.org ), estimates were derived from data gathered from WHO, UNAIDS, Philippine Health Statistics 2011, Philippine Dermatological Society Health Information System database, HIV/AIDS and ART registry of the Philippines, epidemiological studies such as The TREAT Asia HIV Observational Database 2005, and personal communication. Aspergillosis and candidiasis were the top causes of fungal infections in the Philippines. Chronic pulmonary aspergillosis (CPA), drawn from the number of tuberculosis patients, affects 77,172 people. Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) frequencies, which were derived from the number of asthmatic patients, affect 121,113 and 159,869 respectively. Recurrent vulvovaginal candidiasis (RVVC) affects 1,481,899 women. Other estimates were cryptococcal meningitis 84, Pneumocystis pneumonia 391, oral candidiasis 3,467, esophageal candidiasis 1,522 (all in HIV-infected people), invasive aspergillosis (IA) 3,085, candidemia 1,968, candida peritonitis 246, mucormycosis 20, fungal keratitis 358, tinea capitis 846 and mycetoma 97 annually. A total of 1,852,137 (1.9% of population) are afflicted with a serious fungal infection. Epidemiological studies are needed to validate these estimates, facilitating appropriate medical care of patients and proper prioritization of limited resources.

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 Pakistan.

The true burden of fungal infection in Pakistan is unknown. High-risk populations for fungal infections [tuberculosis (TB), diabetes, chronic respiratory diseases, asthma, cancer, transplant and human immunodeficiency virus (HIV) infection] are numerous. Here, we estimate the burden of fungal infections to highlight their public health significance. Whole and at-risk population estimates were obtained from the WHO (TB), BREATHE study (COPD), UNAIDS (HIV), GLOBOCAN (cancer) and Heartfile (diabetes). Published data from Pakistan reporting fungal infections rates in general and specific populations were reviewed and used when applicable. Estimates were made for the whole population or specific populations at risk, as previously described in the LIFE methodology. Of the 184,500,000 people in Pakistan, an estimated 3,280,549 (1.78%) are affected by a serious fungal infection, omitting all cutaneous infection, oral candidiasis and allergic fungal sinusitis, which we could not estimate. Compared with other countries, the rates of candidaemia (21/100,000) and mucormycosis (14/100,000) are estimated to be very high, and are based on data from India. Chronic pulmonary aspergillosis rates are estimated to be high (39/100,000) because of the high TB burden. Invasive aspergillosis was estimated to be around 5.9/100,000. Fungal keratitis is also problematic in Pakistan, with an estimated rate of 44/100,000. Pakistan probably has a high rate of certain life- or sight-threatening fungal infections.

Serious fungal infections in Thailand.

The burden of serious fungal infection in Thailand is increasing but data regarding its incidence and prevalence are lacking. In this study we aimed to estimate the burden of serious fungal diseases in Thailand based on the size of the populations at risk and available epidemiological databases. Data derived from The Bureau of Epidemiology, Department of Disease Control, Thai Ministry of Public Health, World Health Organisation, international and local reports, and some unreported data were used. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Recurrent vulvovaginal candidiasis (>4 episodes per year) is estimated to occur in 3,310 per 100,000 population. Using a previously described rate that 14/10,000 admissions are with fungaemia and 94% of those are Candida, we estimated 8,650 patients with candidaemia. The prevalence of chronic pulmonary aspergillosis is relatively high with a total of 19,044, approximately half subsequent to pulmonary tuberculosis. Invasive aspergillosis is estimated to affect 941 patients following leukaemia therapy, transplantations, and chronic obstructive pulmonary disease, approximately 1.4/100,000. In addition, allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation were estimated at approximately 58.4/100,000 and 77/100,000, respectively. Given approximately 8,134 new cases of AIDS annually, cryptococcal meningitis, Pneumocystis pneumonia, and Talaromyces marneffei infection are estimated at 1.9/100,000, 2.6/100,000, and 0.3/100,000, respectively. The present study indicates that about 1.93% (1,254,562) of the population is affected by serious fungal infections. Owing to the lack of data, reports, and statistics, the number of patients with mycoses in Thailand can only be estimated.

Burden of serious fungal infections in Bangladesh.

In Bangladesh there are several published papers on superficial mycoses. Deep mycoses are also recognized as an important emerging problem. Here, we estimate the annual incidence and prevalence of serious fungal infections in Bangladesh. Demographic data were obtained from world population reports and the data on TB and HIV extracted from the online publications on tuberculosis in Bangladesh and Asia Pacific research statistical data information resources AIDS Data HUB. All the published papers on fungal infections in Bangladesh were identified through extensive search of literature. We estimated the number of affected people from populations at risk and local epidemiological data. Bangladesh has a population of ∼162.6 million, 31% children and only 6% over the age of 60 years. The pulmonary TB caseload reported in 2014 was 119,520, and we estimate a prevalence of 30,178 people with chronic pulmonary aspergillosis, 80% attributable to TB. An anticipated 90,262 and 119,146 patients have allergic bronchopulmonary aspergillosis or severe asthma with fungal sensitization. Only 8,000 people are estimated to be HIV-infected, of whom 2900 are not on ART with a CD4 count <350 µL, Pneumocystis pneumonia and cryptococcal meningitis being rare. Superficial mycoses are very common with Trichophyton rubrum as the predominant etiological agent (80.6%). Numerous cases of mycotic keratitis have been reported from several parts of Bangladesh. Candida bloodstream infection was estimated based on a 5 per 100,000 rate (8100 cases) and invasive aspergillosis based primarily on leukemia and COPD rates, at 5166 cases. Histoplasmosis was documented in 16 cases mostly with disseminated disease and presumed in 21 with HIV infection. This study constitutes the first attempt to estimate the burden of several types of serious fungal infections in Bangladesh.

Serious fungal infections in Peru.

Epidemiological data about mycotic diseases are limited in Peru and estimation of the fungal burden has not been previously attempted. Data were obtained from the Peruvian National Institute of Statistics and Informatics, UNAIDS and from the Ministry of Health's publications. We also searched the bibliography for Peruvian data on mycotic diseases, asthma, COPD, cancer and transplants. Incidence or prevalence for each fungal disease were estimated in specific populations at risk. The Peruvian population for 2015 was 31,151,543. In 2014, the estimated number of HIV/AIDS and pulmonary tuberculosis cases was 88,625, 38,581 of them not on ART, and 22,027, respectively. A total of 581,174 cases of fungal diseases were estimated, representing approximately 1.9% of the Peruvian population. This figure includes 498,606, 17,361 and 4,431 vulvovaginal, oral and esophageal candidiasis, respectively, 1,557 candidemia cases, 3,593 CPA, 1,621 invasive aspergillosis, 22,453 allergic bronchopulmonary aspergilllosis, 29,638 severe asthma with fungal sensitization, and 1,447 Pneumocystis pneumonia. This first attempt to assess the fungal burden in Peru needs to be refined. We believe the figure obtained is an underestimation, because of under diagnosis, non-mandatory reporting and lack of a surveillance system and of good data about the size of populations at risk.

The burden of serious fungal diseases in Russia.

The incidence and prevalence of fungal infections in Russia is unknown. We estimated the burden of fungal infections in Russia according to the methodology of the LIFE program (www.LIFE-worldwide.org). The total number of patients with serious and chronic mycoses in Russia in 2011 was three million. Most of these patients (2,607,494) had superficial fungal infections (recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis with HIV infection and tinea capitis). Invasive and chronic fungal infections (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia) affected 69,331 patients. The total number of adults with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation was 406,082.

Estimating the burden of fungal disease in Vietnam.

Data regarding the prevalence of fungal infections in Vietnam are limited yet they are likely to occur more frequently as increasingly sophisticated healthcare creates more iatrogenic risk factors. In this study, we sought to estimate baseline incidence and prevalence of selected serious fungal infections for the year 2012. We made estimates with a previously described actuarial method, using reports on the incidence and prevalence of various established risk factors for fungal infections from Vietnam, or similar environments, supplemented by personal communications. Global data were used if local data were unavailable. We estimated 2,352,748 episodes of serious fungal infection occurred in Vietnam in 2012. Frequent conditions included recurrent vaginal candidiasis (3893/100,000 women annually), tinea capitis (457/100,000 annually) and chronic pulmonary aspergillosis (61/100,000/5 year period). We estimated 140 cases of cryptococcal meningitis, 206 of penicilliosis and 608 of Pneumocystis jirovecii pneumonia. This is the first summary of Vietnamese fungal infections. The majority of severe disease is due to Aspergillus species, driven by the high prevalence of pulmonary tuberculosis. The AIDS epidemic highlights opportunistic infections, such as penicilliosis and cryptococcosis, which may complicate immunosuppressive treatments. These estimates provide a useful indication of disease prevalence to inform future research and resource allocation but should be verified by further epidemiological approaches.

Prevalence of chronic pulmonary aspergillosis in patients with tuberculosis from Iran.

In patients with preexisting lung disease, especially a cavity, Aspergillus can infect the surface of the cavity, causing chronic cavitary pulmonary aspergillosis (CCPA), and may form an aspergilloma, collectively called chronic pulmonary aspergillosis (CPA). In the present study, we assessed tuberculosis (TB) patients for CPA based on culture and serological methods. During a period of 1 year (from March 2013 to March 2014), we studied 124 patients with TB (94 with current TB and 30 with previous TB) at Masih Daneshvari Hospital in Tehran, Iran. Sputum specimens were analyzed by direct microscopic examination (DME) and fungal culture. The clinical and radiological features of all patients were recorded, to categorize the patients into CCPA and aspergilloma. All patients were screened for serum-specific IgG against A. fumigatus, by enzyme-linked immunosorbent assay (ELISA). Out of 124 patients with TB (66 male, age range: 10-91 years), 48 patients (38.7 %) exhibited residual cavities. Eighteen (14.5 %) patients had cavities with pleural thickening. A round-shaped mass lesion was detected in six patients (6.8 %). DME was positive in ten patients for septate fungal hyphae. A. fumigatus was grown from 14 samples. Fifty-five (44.3 %) cases were positive for serum-specific IgG against A. fumigatus. Of 124 patients with TB, 3 (2.4 %) met criteria for aspergilloma and 14 (11.3 %) for CCPA. CPA is a common clinical presentation in individuals with healed TB in Iran, as reported by previous studies from other countries.

Reduced expression of TLR3, TLR10 and TREM1 by human macrophages in Chronic cavitary pulmonary aspergillosis, and novel associations of VEGFA, DENND1B and PLAT.

Chronic cavitary pulmonary aspergillosis (CCPA) is an uncommon but serious pulmonary disease of humans, with an annual mortality rate of 10-30%. It is caused by the fungus Aspergillus fumigatus. Patients are overtly immunocompetent; however, some immunogenetic defect is likely. To investigate this, we performed a genetic association study analysing biologically plausible candidate genes in 112 CCPA patients and 279 healthy controls, and investigated gene expression in monocyte-derived macrophages from patients and controls at baseline and during stimulation with A. fumigatus. Single-nucleotide polymorphisms (SNPs) associated with CCPA were found in TLR1, CLEC7A (dectin-1), PLAT (n=2), VEGFA, and DENND1B. Macrophages from CCPA patients showed low TLR3 and TLR10 expression and high TREM1 expression at baseline, as compared with macrophages from healthy subjects, with major expression differences being seen in most Toll-like receptors (TLRs) during 9 h of co-culture with A. fumigatus. The differences in baseline expression between the healthy and CCPA groups suggest roles for TLR3 and TLR10 in susceptibility to CCPA, and the association of SNPs in PLAT (n=2), VEGFA and DENND1B supports novel roles for plasminogen activation and angiogenesis and of these genes specifically in susceptibility to CCPA.

A prominent role for the IL1 pathway and IL15 in susceptibility to chronic cavitary pulmonary aspergillosis.

Chronic cavitary pulmonary aspergillosis (CCPA) is a progressive lung condition with a 10-30% annual mortality. Although overtly immunocompetent, some immunogenetic defect in patients is likely. To investigate a possible immunogenetic defect in CCPA, we analysed biologically plausible candidate genes in 112 CCPA patients and 279 healthy controls in a genetic association study of genes involved in the post-recognition immune response to Aspergillus fumigatus. We also compared gene expression in monocyte-derived macrophages from subjects with and without disease, both at baseline and during stimulation with A. fumigatus. Compared with macrophages from healthy subjects, CCPA macrophages showed unrestrained rises in IL1A, IL1B, IL6, IRAK2 and TRAF6 throughout the experiment, and a lack of expression of TGFB1 at 9 h. Single nucleotide polymorphisms (SNPs) associated with CCPA were found in IL1B (n = 2), IL1RN and IL15 (n = 3). Uncontrolled expression of IL1 and IL6 and continuing high levels of these cytokines may result in continuing cellular influx and pro-inflammatory responses, inhibiting disease resolution and contributing to disease progression in CCPA. The association of SNPs in IL1B, IL1RN and IL15 with CCPA supports a role for the IL1 pathway, as well as implicating the IL15 gene, in susceptibility to CCPA.