Capsulatum Var Research Articles

African histoplasmosis: new clinical and microbiological insights.

African histoplasmosis is defined as the fungal infection caused by Histoplasma capsulatum var. duboisii (Hcd). Studies focused on distinguishing Hcd and H. capsulatum var. capsulatum (Hcc), which coexist in Africa, are scarce or outdated, and African strains are continuously underrepresented. In this work, 13 cases of African patients with histoplasmosis diagnosed in the Spanish Mycology Reference Laboratory have been reviewed showing that 77% had disseminated disease and AIDS as underlying disease although Hcd infection has been classically considered a rare presentation in AIDS patients. Strains isolated from these patients and other clinical and reference strains were studied by assessing classical identification methods and performing a three-loci multi-locus sequence analysis (MLSA). Classical identification methods based on biochemical tests and measurement of yeast size proved to be useless in distinguishing both varieties. The MLSA defined an African cluster, with a strong statistical support, that included all strains with African origin. Finally, mating type was also determined by using molecular methods revealing an unequal mating type distribution in African strains. In conclusion, historical statements and classical identification methods were useless to distinguish between varieties, whereas molecular analyses revealed that all strains with African origin grouped together suggesting that traditional classification should be revised. Further investigation is required in order to unravel traditional concepts about Hcd infection and support results obtained in this work.

Eficacia del tratamiento y de la profilaxis antifúngica secundaria en la histoplasmosis asociada al sida. Experiencia del Hospital de Infecciosas Francisco J. Muñiz, de la ciudad de Buenos Aires

BackgroundClassic histoplasmosis is a systemic endemic mycosis due to Histoplasma capsulatum var. capsulatum. A significant reduction in the morbidity and mortality of AIDS-related histoplasmosis has been observed since the introduction of highly active antiretroviral therapy (HAART) and secondary antifungal prophylaxis. AimsThe aim of this study was to determine the current state of prognosis and treatment response of HIV-positive patients with histoplasmosis in the Francisco J. Muñiz Infectious Diseases Hospital in Buenos Aires City. MethodsA retrospective study was conducted using the demographic, clinical, immunological and treatment data of 80 patients suffering from AIDS-related histoplasmosis. ResultsOf the 80 cases studied 65 were male, the median age was 36 years, with 73.7% of the patients being drug addicts, 82.5% of the patients was not receiving HAART at diagnosis, and 58.7% of the cases had less than 50 CD4+ cells/μl at the beginning of the treatment. The initial phase of treatment consisted of intravenous amphotericin B and/or oral itraconazole for 3 months, with 78.7% of the cases showing a good clinical response. Only 26/63 patients who were discharged from hospital continued with the follow-up of the HAART, secondary prophylaxis with itraconazole or amphotericin B. Secondary prophylaxis was stopped after more than one year of HAART if the patients were asymptomatic, had two CD4+ cell counts greater than 150cells/μl, and undetectable viral loads. No relapses were observed during a two-year follow up after prophylaxis was stopped. ConclusionsThe treatment of histoplasmosis in HIV-positive patients was effective in 78.8% of the cases. The combination of HAART and secondary antifungal prophylaxis is safe, well tolerated, and effective. The low adherence of patients to HAART and the lack of laboratory kits for rapid histoplasmosis diagnosis should be addressed in the future. The usefulness of primary antifungal prophylaxis for cryptococcosis and histoplasmosis HIV-positive patients should be studied.

Development and Evaluation of a Molecular Diagnostic Method for Rapid Detection of Histoplasma capsulatum var. farciminosum, the Causative Agent of Epizootic Lymphangitis, in Equine Clinical Samples.

Histoplasma capsulatum var. farciminosum, the causative agent of epizootic lymphangitis (EZL), is endemic in parts of Africa. Diagnosis based on clinical signs and microscopy lacks specificity and is a barrier to further understanding this neglected disease. Here, a nested PCR method targeting the internal transcribed spacer (ITS) region of the rRNA operon was validated for application to equine clinical samples. Twenty-nine horses with signs of EZL from different climatic regions of Ethiopia were clinically examined. Blood samples and aspirates of pus from cutaneous nodules were taken, along with blood from a further 20 horses with no cutaneous EZL lesions. Among the 29 horses with suspected cases of EZL, H. capsulatum var. farciminosum was confirmed by extraction of DNA from pus and blood samples from 25 and 17 horses, respectively. Positive PCR results were also obtained with heat-inactivated pus (24 horses) and blood (23 horses) spotted onto Whatman FTA cards. Two positive results were obtained among blood samples from 20 horses that did not exhibit clinical signs of EZL. These are the first reports of the direct detection of H. capsulatum var. farciminosum in equine blood and at high frequency among horses exhibiting cutaneous lesions. The nested PCR outperformed conventional microscopic diagnosis, as characteristic yeast cells could be observed only in 14 pus samples. The presence of H. capsulatum var. farciminosum DNA was confirmed by sequencing the cloned PCR products, and while alignment of the ITS amplicons showed very little sequence variation, there was preliminary single nucleotide polymorphism-based evidence for the existence of two subgroups of H. capsulatum var. farciminosum. This molecular diagnostic method now permits investigation of the epidemiology of EZL.

"An In-Vitro Trial on Antifungal Effect of Xanthium Strumarium Leaf Extract on the Growth of the Mycelial form of Histoplasma Capsulatum Var Farciminosum Isolated from Horse"

"An In-Vitro Trial on Antifungal Effect of Xanthium Strumarium Leaf Extract on the Growth of the Mycelial form of Histoplasma Capsulatum Var Farciminosum Isolated from Horse"

Histoplasma capsulatumInfection with Extensive Lytic Bone Lesions Mimicking LCH

Multiple lytic bone lesions in a child can be a manifestation of various diseases like Langerhans cell histiocytosis, metastatic neuroblastoma, leukemia, hyperparathyroidism, multifocal osteomyelitis and histoplasmosis. Disseminated histoplasmosis caused by Histoplasma capsulatum var. duboisii is well known to present with multiple osteolytic lesions in immunocompromised adults and is mostly restricted to the African subcontinent. Histoplasmosis seen in American and Asian countries is caused by Histoplasma capsulatum var. capsulatum, which presents with pulmonary and systemic manifestations and rarely bone involvement. We report a case of histoplasmosis, caused by H. capsulatum var. capsulatum with extensive lytic bone lesions in a 13 year old immunocompetent boy who presented with prolonged fever, weight loss and multiple boggy swellings. He responded to amphotericin and is currently on Itraconazole. This case is unique for extensive osteolytic lesions with H. capsulatum var. capsulatum infection in an immunocompetent child.

Histoplasmose multifocale à Histoplasma capsulatum var. duboisii chez un Sénégalais de 22 ans sans immunodépression prouvée

The authors report a case of multifocal African histoplasmosis with polymorphic skin involvement occuring in a patient without proven immunosuppression. He was a young 22-year-old patient from eastern Senegal -but born in Ouganda- who presented with polymorphic skin lesions: ombilicated papulo-nodules, gums and ulcerative and budding lesions. He showed lymphadenopathies without clinical inflammation and with a cheesy appearance of the biopsy but without tuberculosis and also hepatosplenic and bone involvement. Mycological samples of the skin and lymph nodes biopsies revealed yeasts of Histoplasma capsulatum var. duboisii with a positive culture on Sabouraud medium. HIV serology, HTLV1et 2, the serum proteins electrophoresis were unremarkable. Treatment with amphotericin B was irregular because of its inaccessibility in the national territory and its cost. The patient died of sepsis together with the aggravation of his disease.

Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment.

Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a human systemic mycosis with worldwide distribution. In the present work, we demonstrate that H. capsulatum yeasts are able to induce cytokine secretion by the human lung epithelial cell line A549 in integrin- and Src-family kinase (SFK)-dependent manners. This conclusion is supported by small interfering RNA (siRNA) directed to α3 and α5 integrins, and PP2, an inhibitor of SFK activation. siRNA and PP2 reduced IL-6 and IL-8 secretion in H. capsulatum-infected A549 cell cultures. In addition, α3 and α5 integrins from A549 cells were capable of associating with H. capsulatum yeasts, and this fungus promotes recruitment of these integrins and SFKs to A549 cell membrane rafts. Corroborating this finding, membrane raft disruption with the cholesterol-chelator methyl-β-cyclodextrin reduced the levels of integrins and SFKs in these cell membrane domains. Finally, pretreatment of A549 cells with the cholesterol-binding compound, and also a membrane raft disruptor, filipin, significantly reduced IL-6 and IL-8 levels in A549-H.capsulatum cultures. Taken together, these results indicate that H. capsulatum yeasts induce secretion of IL-6 and IL-8 in human lung epithelial cells by interacting with α3 and α5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation.

A novel molecular diagnostic tool for Equine Arteritis Virus detection and characterization

Histoplasma capsulatum var. farciminosum (HCF), causing Epizootic Lymphangitis (EZL), is endemic in parts of Africa including, Ethiopia, Senegal and Gambia. Despite its high prevalence, impact on animal welfare and socio-economic importance, there is little evidence upon which to build contextually relevant disease control programmes. The performance and availability of diagnostic tests currently used by clinicians is problematic. Methods such as pattern recognition of clinical signs and microscopy lack sensitivity, and other options are either not commercially available or not readily feasible (e.g. culture). This is a significant barrier to further understanding this disease within endemic countries. This study aimed to validate a nested PCR method to confirm the presence of HCF in equine clinical samples. Ethical approval was obtained from the University of Liverpool and the College of Veterinary Medicine and Agriculture. Twenty-nine horses with suspected EZL were included from topographically varied regions of Ethiopia. Clinical examination was recorded and lesion locations drawn onto equine silhouettes. Blood samples and aspirates of pus from unruptured cutaneous nodules were obtained before treatment provided by SPANA. Blood and clinical data were collected from a further 20 horses with no cutaneous EZL lesions. Giemsa stained impression smears of pus and blood were examined microscopically. Aliquots of heat-inactivated pus and blood were inoculated onto Whatman FTA cards and imported to the UK with Defra approved licensing. A nested PCR targeting the ITS region*, was used to identify samples containing HCF, and all PCR products were sequenced. HCF was confirmed in FTA card pus samples from 24 horses, additionally, 23 blood samples were positive from EZL suspected cases. The nested PCR compared favourably overmicroscopic examination of pus, where characteristic HCF yeast bodies were detected in only 14 of the 24 PCR positive samples examined. All nested PCR amplification products were confirmed as Histoplasma spp. by sequencing. Sequencing of cloned PCR amplicons suggested at least two subgroups of HCF based on single nucleotide polymorphisms. These techniques allow the rapid diagnosis of HCF directly from equine clinical samples and offer a useful epidemiological tool. The identification of HCF in blood raises questions about the pathogenesis of HCF in horses and warrants further investigation. *Jiang, B. et. al. (2000) Journal of clinical microbiology 38 (1): 241245. We gratefully acknowledge funding awarded by SPANA UK, the SPANA Ethiopia team for assisting in sampling, and all participating horse-owners. Additional funds were awarded by the Institute of Infection and Global Health, and an SFAM studentship.

The Effect of Combretum molle Seed Extracts on the Growth of the Mycelial Form of Histoplasma capsulatum Var Farciminosum-an In Vitro Trial

Epizootic lymphangitis (EL) compromises the welfare of working horses and has a serious negative impact on the livelihoods of cart horse owners/drivers in the affected parts of Ethiopia. Unfortunately, antifungal drugs for the treatment of EL are unavailable in both private and government clinics. The spread of multidrug-resistant strains of fungi motivates to discover new classes of antifungal compounds that inhibit these resistant strains. Therapeutic alternative compounds, particularly those isolated from plants have shown promising empirical effect on different fungal strains, which are unresponsive to chemical anti fungi drugs. Histoplasma capsulatum var farciminosum obtained from Aklilu Lema Institue of Patho Biology (ALIPB) was used as test organism. Agar dilution assay was performed to evaluate the inhibitory effect of Combretum molle seed extract and to measure the minimum inhibitory concentration (MIC). Ketaconazole was used as a positive control. Combretum molle seed extracts inhibit the growth of HCF up to 0.0156%. Hydrolysable tannins have a great potential in inhibition of fungal growth. In case of topical application, tannins have haemostatic effect and wound closure property

Study on Epidemiology and Socioeconomic Impact of Epizootic Lymphangitis in Carthorses in Southwestern Shoa

A study was conducted between December 2008 and April 2009 on 705 carthorses in three towns of Southwestern Ethiopia namely Sebeta, Asgori and Woliso to investigate the Epidemiology and Socioeconomic impact of Epizootic lymphangitis (EL). The study has revealed an overall prevalence of 25.1% (177/705). There was no statistically significant (X 2 =3.88, P> 0.05) difference on the occurrence of the disease in the three districts. The highest prevalence being observed at Woliso with 27.9% and the lowest was at Sebeta with 20.2%. The result of histopathological and mycological examinations has revealed characte ristic features of HCF. Result of differential leukocyte count had shown a statistical significant difference across the severity of the disease and neutrophil count (r=0.87, F=6.08, P<0.005) while lymphocyte count were inversely related to the severity st age of the disease (r=0.94.F=23.28, P<0.001). The yeast forms of Histoplasma capsulatum var. farciminosum were isolated on the sabouraud’s dextrose agar. The result of questionnaire survey from 35 carthorse owners indicates that EL was the first and the ma jor important disease of carthorses by creating a negative impact on the economy of the carters. Despite its impact, awareness on the transmission and control mechanism of the disease was not uniformly known by the carthorse owners. Therefore, further stud y on the extent of the disease and educating the owners both on the disease and its way of transmission was recommended.

Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro

Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1μgmL−1 for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4μgmL−1and from 0.0625 to 1μgmL−1 for filamentous and yeast phase, respectively. Concerning the antifungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125μgmL−1 and from 0.0039 to 0.0312μgmL−1 for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p<0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum.

Development and Evaluation of A Molecular Diagnostic Method to Rapidly Detect Histoplasma Capsulatum Var. Farciminosum (Causing Epizootic Lymphangitis) from Equine Clinical Samples

Reasons for performing studyHistoplasma capsulatum var. farciminosum (HCF), causing epizootic lymphangitis (EZL), is endemic in parts of Africa including, Ethiopia, Senegal and Gambia. Despite its high prevalence, impact on animal welfare and socio‐economic importance, there is little evidence upon which to build practical disease control strategies. The performance and availability of diagnostic tests currently used by clinicians is problematic. Methods such as pattern recognition of clinical signs and microscopy lack specificity and other reported methods are either not commercially available or not readily feasible in these settings (e.g. culture). This is a significant barrier to further understanding this disease within endemic countries.ObjectivesTo validate a nested PCR method to confirm the presence of HCF in equine clinical samples.Study designCross‐sectional.MethodsTwenty‐nine horses with suspected EZL were included from topographically varied regions of Ethiopia. Clinical data, lesion location drawn onto equine silhouettes, blood samples and aspirates of pus from cutaneous nodules were obtained before treatment provided by SPANA clinic. Blood and clinical data were collected from a further 20 horses with no cutaneous EZL lesions. Giemsa stained impression smears of pus were examined microscopically. Aliquots of heat‐inactivated pus and blood were inoculated onto Whatman FTA cards and imported to the UK with Defra approved licensing. A nested PCR targeting the ITS region, was used to identify samples containing HCF and PCR products were sequenced.ResultsHCF was confirmed in heat‐inactivated FTA card pus samples from 24 horses, additionally, 23 blood samples were positive from EZL suspected cases. Bioinfomatic analyses suggested that there was diversity within the ITS region among these HCF products.ConclusionsThese PCR techniques allow the rapid diagnosis of HCF directly from equine clinical samples. The identification of HCF in blood raises questions about the pathogenesis of HCF in horses and warrants further investigation.AcknowledgementsWe thank the SPANA Ethiopia team; participating cart‐horse owners; the Ethio‐Belgian project; Addis Ababa University; Gabrielle Laing and the PHE UK Mycology reference laboratory.Ethical animal research: Ethical approval for the project was awarded from the University of Liverpool and The College of Veterinary Medicine and Agriculture, Addis Ababa University. Sources of funding: SPANA UK (registered charity), the Institute of Infection and Global Health, University of Liverpool and an Sfam studentship. Competing interests: Dr Stringer was veterinary director at SPANA while this project was conducted and provided consultative and logistical input.

Champignons non dermatophytiques et non candidosiques isolés au CHU Le Dantec de Dakar en 2014 : étude épidémiologique, clinique et mycologique

In recent years, the incidence of superficial fungal infections involving nondermatophytic and noncandidal fungi increased considerably. The objective of this work was to analyze the epidemiological, clinical and mycological fungal infections due to nondermatophytic and noncandidal fungi diagnosed in the laboratory of parasitology-mycology of Le Dantec hospital in Dakar. With a retrospective study of the various cases of nondermatophytic and noncandidal fungi isolated in the laboratory of parasitology-mycology during the period of November 2013 to December 2014, we collected 22 cases of infections in 11 men and 11 women; age ranging from 17 to 75 years with a mean of 45.3 years (sex ratio=1): eight cases of intertrigo, seven cases of onychomycosis, four cases of palmoplantar keratoderma (KPP), a case of onychomycosis associated with interdigital intertrigo, a case of infectious myositis and one case of African histoplasmosis. We have isolated and identified a total of 22 nondermatophytic and noncandidal fungi: ten Fusarium, five Trichosporon, two Chrysosporium, two Geotrichum, one Rhodotorula, one Neoscytalidium dimidiatum and one Histoplasma capsulatum var. duboisii. So we are seeing the emergence of nondermatophytic and noncandidal increasingly isolated from superficial and local lesions. These fungi, generally contaminants or commensal, cause a problem regarding their direct involvement in pathological processes in which they are isolated. So we should respect the recommendations proposed for their involvement in pathological processes and, by a collaboration between clinician and biologist, demonstrate their real involvement through effective, targeted treatment.

Disseminated histoplasmosis caused by Histoplasma capsulatum var. duboisii in a non-HIV patient in Burkina Faso: Case report

Histoplasmosis is a fungal infection due to Histoplasma capsulatum. The African form of this mycosis, caused by Histoplasma capsulatum var. duboisii, remains rare. We report a case of disseminated African histoplasmosis with skin, lymph nodes, bones and viscera localizations. The 22-year-old patient was HIV-seronegative and was considered immunocompetent. The presence of Histoplasma capsulatum var duboisii in ulcerations and a nodule pus aspiration was confirmed by direct microscopic examination and by culture. The medical treatment was based on fluconazole. Even though a regression of the symptoms was observed, the patient died. In disseminated African histoplasmosis, an early laboratory diagnosis must be carried out for accurate treatment.

Histoplasma capsulatum in planktonic and biofilm forms: in vitro susceptibility to amphotericin B, itraconazole and farnesol.

It is believed that most microbial infections are caused by pathogens organized in biofilms. Recently, it was shown that the dimorphic fungus Histoplasma capsulatum, estimated to be the most common cause of fungal respiratory diseases, is also able to form biofilm. Although the antifungal therapy commonly used is effective, refractory cases and recurrences have been reported. In the search for new compounds with antimicrobial activity, the sesquiterpene farnesol has gained prominence for its antifungal action. This study aimed to evaluate the in vitro susceptibility of H. capsulatum var. capsulatum to the antifungal agents itraconazole and amphotericin B, and farnesol alone and combined, as well as to determine the in vitro antifungal activity of these compounds against biofilms of this pathogen. The results show that farnesol has antifungal activity against H. capsulatum in the yeast and filamentous phases, with MIC values ranging from 0.0078 to 0.00312 µM. A synergistic effect (fractional inhibitory concentration index ≤0.5) between itraconazole and farnesol was found against 100 and 83.3 % of the isolates in yeast and mycelial forms, respectively, while synergism between amphotericin B and farnesol was only observed against 37.5 and 44.4 % of the isolates in yeast and filamentous forms, respectively. Afterwards, the antifungal drugs, itraconazole and amphotericin B, and farnesol alone, and the combination of itraconazole and farnesol, were tested against mature biofilms of H. capsulatum, through XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) metabolic assay, and the itraconazole and amphotericin B showed lower antibiofilm activity when compared to farnesol alone and farnesol combined with itraconazole. In conclusion, farnesol showed promising results as an antifungal agent against H. capsulatum and also showed adjuvant action, especially when combined with itraconazole, increasing the fungal susceptibility to this drug.

HIV-associated disseminated histoplasmosis in western French Guiana, 2002-2012.

Disseminated histoplasmosis (DH) is the most current revelation mode of AIDS in French Guiana. We describe the clinical and paraclinical presentation of DH, diagnostic tools, evolution and factors associated with 1-year mortality in HIV-infected patients from western French Guiana. Microbiologically proven AIDS-related DH in Saint Laurent du Maroni's hospital between May 2002 and May 2012 were retrospectively included. Among the 82 patients included, 58 (71%) were male, 44 (53%) presented concurrent histoplasmosis and HIV diagnosis and 63 (80%) had a CD4 cell count under 50 cells μL(-1). Almost all patients had weight loss (97%) and fever (95%), while 84% had digestive symptoms (63% diarrhoea), 55% lymphadenopathy, and 49% respiratory symptoms. Documented and presumed locations of H. capsulatum var capsulatum (Hcc) concerned almost all organs, with a particular affinity for the bone marrow and the digestive system. Co-infections were associated in 65%. Following treatment initiation, 10 patients (13%) died within 1 month and 17 patients (25%) died within a year. DH is a polymorphous systemic mycosis with haematological and digestive tropism. Co-infections are frequent and mortality rate is high.

Fluorescent in situ hybridization of pre-incubated blood culture material for the rapid diagnosis of histoplasmosis.

Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of Candida and Cryptococcus species in blood culture materials. FISH procedures for the detection of Histoplasma capsulatum var. capsulatum have not been reported so far. This study describes the development and evaluation of fluorescently labeled rRNA-targeting FISH probes to detect and identify H. capsulatum in blood cultures. All three analyzed H. capsulatum reference strains and clinical isolates showed positive signals with the newly designed specific oligonucleotide probes for H. capsulatum, whereas negative reactions were observed for all three nontarget yeast species and the two nontarget bacteria. The assay was also successfully applied for detections of H. capsulatum cells in pre-incubated blood culture samples of patients with clinical suspicion of histoplasmosis (n = 33). The described FISH-based assay was shown to be easy to apply, sensitive, and specific (compared to polymerase chain reaction) for the detection and identification of H. capsulatum in this proof-of-principle analysis. Larger multicentric assessments are recommended for a thorough diagnostic evaluation of the procedure.

Imported African Histoplasmosis in an Immunocompetent Patient 40 Years after Staying in a Disease-Endemic Area

Histoplasmosis caused by Histoplasma capsulatum var. duboisii is a rare disease outside central and western Africa. In Europe, all cases are imported. We report a case of an African histoplasmosis with isolated pulmonary involvement in a non-immunocompromised patient that occurred 40 years after his stay in a disease-endemic area. The patient was given itraconazole. (18)F-fluoro-2-deoxy-d-glucose positron emission tomography-computed tomography was used to assess evolution during treatment. The outcome for the patient was favorable.

Late occurrence of Histoplasma duboisii cutaneous and pulmonary infection 18 years after exposure

We report an imported case of Histoplasma capsulatum var. duboisii (H. duboisii) infection in a white French woman revealed by cutaneous lesions of the scalp, 18 years after her last stay in West and Central Africa. Asymptomatic bilateral pulmonary infiltrates were discovered on thoracic computed tomography. Skin biopsy allowed the positive diagnosis showing the typical yeasts; culture of biopsy specimens was positive for H. capsulatum. In the absence of criteria of severity, the patient was treated for one year with oral itraconazole 400mg/day. The outcome was favourable, skin and pulmonary lesions resolved slowly. The follow up is 5 years without relapse after the end of treatment. This case illustrates the possibility of late occurrence of H. duboisii infection, many years after exposure and the major importance of asking any patient for travelling or residency in tropical countries.

HIV-associated histoplasmosis early mortality and incidence trends: from neglect to priority.

BackgroundHistoplasmosis is an endemic fungal infection in French Guiana. It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths. Diagnosis is difficult, but in the past 2 decades, it has improved in this French overseas territory which offers an interesting model of Amazonian pathogen ecology. The objectives of the present study were to describe the temporal trends of incidence and mortality indicators for HIV-associated histoplasmosis in French Guiana.MethodsA retrospective study was conducted to describe early mortality rates observed in persons diagnosed with incident cases of HIV-associated Histoplasma capsulatum var. capsulatum histoplasmosis admitted in one of the three main hospitals in French Guiana between 1992 and 2011. Early mortality was defined by death occurring within 30 days after antifungal treatment initiation. Data were collected on standardized case report forms and analysed using standard statistical methods.ResultsThere were 124 deaths (45.3%) and 46 early deaths (16.8%) among 274 patients. Three time periods of particular interest were identified: 1992–1997, 1998–2004 and 2005–2011. The two main temporal trends were: the proportion of early deaths among annual incident histoplasmosis cases significantly declined four fold (χ2, p<0.0001) and the number of annual incident histoplasmosis cases increased three fold between 1992–1997 and 1998–2004, and subsequently stabilized.ConclusionFrom an occasional exotic diagnosis, AIDS-related histoplasmosis became the top AIDS-defining event in French Guiana. This was accompanied by a spectacular decrease of early mortality related to histoplasmosis, consistent with North American reference center mortality rates. The present example testifies that rapid progress could be at reach if awareness increases and leads to clinical and laboratory capacity building in order to diagnose and treat this curable disease.