Histoplasmosis and Thrombocytopenic Purpura: Transmission by Renal Homotransplantation

Two patients with disseminated histoplasmosis are reported. One patient presented with severe thrombocytopenic purpura and splenomegaly. Histoplasmin skin test, blood and bone marrow cultures and smears, sputum cultures, and chest radiographs were negative for Histoplasma capsulatum. She died on the sixth hospital day from a massive intracerebral hemorrhage. Cardiorespiratory function was maintained until one kidney was removed for homotransplantation. The second patient, with chronic glomerulonephritis and uremia, received the renal homograft from the first patient. Initial signs of homograft rejection developed five days postoperatively. Diffuse thrombocytopenic purpura occurred shortly thereafter. Spores of Histoplasma capsulatum were observed in blood smears, in leukocyte concentrates, and in five-day leukocyte cultures from the blood obtained prior to death. Disseminated histoplasmosis was found in both patients at autopsy. The severe platelet deficit in both cases suggests that systemic histoplasmosis should be considered as a cause of thrombocytopenic purpura.To our knowledge, this is the first reported instance of direct transmission of Histoplasma capsulatum, and must be considered a hazard in homotransplantation.In vitro leukocyte cultures as a method for early diagnosis of certain disseminated fungous infections needs further investigation.     

Gastrointestinal Histoplasmosis in a Hepatitis C-Infected Individual

Gastrointestinal histoplasmosis is a rare manifestation of this fungal infection, typically identified in immunocompromised patients, such as those with HIV/AIDS. Here, we report a case of disseminated histoplasmosis with gastrointestinal involvement in a Hepatitis C-infected patient. The fungal agent was confirmed to be Histoplasma capsulatum by a DNA probe assay performed on a bone marrow sample. We propose that this fungal disease should be kept on the differential of patients infected with the Hepatitis C virus, as it has been reported to have numerous damaging effects on the adaptive immune system.     

An unusual presentation of disseminated histoplasmosis in a non-HIV patient from Vietnam

BackgroundHistoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum, naturally found in nitrogen-rich soil, whose main transmission route is the inhalation of conidia. Up to 95% of histoplasmosis cases are asymptomatic or transient, and the remaining 5% of cases have pathological manifestations in the lungs, bone marrow, liver, spleen, intestine, mucous membranes, and rarely on the skin. This mycosis has been reported from many endemic areas, mainly in immunosuppressed patients, such as HIV-positive patients, and its disseminated form is rarely reported.Case reportHistoplama capsulatum was isolated and identified by means of microscopy, culture characteristics and nested PCR from the cutaneous lesions of a non-HIV patient from Vietnam. The patient improved significantly with systemic itraconazole treatment.ConclusionsDisseminated histoplasmosis with cutaneous involvement in non-HIV patients is an extremely unusual presentation.     

How I Treat Histoplasmosis

Histoplasmosis is an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. Some important manifestations of infection include acute or chronic pulmonary disease, histoplasmomas, progressive disseminated histoplasmosis, and central nervous system infection. Depending on the clinical presentation, site of infection and severity of disease, either amphotericin B preparations followed by itraconazole, or itraconazole alone have become the preferred treatments. Because prolonged therapy (6 weeks to 24 months) may be required, careful monitoring for nephrotoxicity in patients on amphotericin B preparations is necessary. In addition, in patients receiving itraconazole, vigilance for drug interactions and pharmacokinetic properties is warranted. Histoplasma antigen testing has improved rapidity of diagnosis and the ability of long-term monitoring for clinical response in patients with histoplasmosis.     

Histoplasmosis: cytodiagnosis and review of literature with special emphasis on differential diagnosis on cytomorphology

N. Gupta, S. K. Arora, A. Rajwanshi, R. Nijhawan and R. Srinivasan
Histoplasmosis: cytodiagnosis and review of literature with special emphasis on differential diagnosis on cytomorphology Background: Human infection with Histoplasma capsulatum runs the gamut from asymptomatic to disseminated disease. In immunocompromised patients, a tiny inoculum can lead to widespread disseminated infection. Early diagnosis and initiation of treatment is therefore important. Objective: To review the cases of histoplasmosis diagnosed on fine needle aspiration cytology (FNAC) and to discuss the clinical presentation, associated inflammatory response, load of organisms and differential diagnosis on cytomorphology in these cases. Methods: Retrospective review of seven cases of histoplasmosis at a tertiary‐care centre during the period from 1998 to 2009 was performed. Clinical presentation along with cytomorphological features were studied and discussed in detail. Results: The mean age of patients was 48.6 years and six out of seven were male. History of immunodeficiency (HIV) was available in five cases. Six patients presented with peripheral and/or abdominal lymphadenopathy. One patient had nodular shadows in both lungs and two also had skin lesions. On cytological smears, a variable load of uniform round to oval, about 2–4 μm in diameter, budding yeasts were seen intracellularly (within histiocytes) as well as extracellularly. In one case (HIV positive), these organisms were also seen within neutrophil polymorphonuclear leucocytes. In two cases, an inflammatory response in the form of epithelioid cell granulomas along with multinucleated giant cells was seen. Conclusions: FNAC is a reliable tool to recognize infection with H. capsulatum in tissues. This infection can cause a variable inflammatory response, which should be considered while reporting on such cases.     

Histoplasmosis as cause of penile ulcer in acquired immune deficiency syndrome (AIDS): three case reports

Background Histoplasma capsulatum is the causative agent of American histoplasmosis. The relationship between disseminated histoplasmosis and AIDS has been well established. Widespread hematogenous dissemination of Histoplasma capsulatum in HIV positive patients can cause a plethora of clinical manifestations; virtually any organic system can be affected. However, genital ulceration by H. capsulatum in patients with AIDS is a real challenge during investigation of the infection due to the great variety of differential diagnoses that are involved. Method The diagnosis was performed by histopathologic study; H. capsulatum was detected by silver staining (Grocott staining) and confirmed by immunocytochemistry. Results We report three cases of histoplasmosis in patients with AIDS, in which we observed genital ulcers, an unusual form of presentation of this disease. In one of these cases, the treatment resulted in total cure. Conclusion The cases reported herein are to illustrate the plurality of pathologies and clinical manifestations, which may affect immunocompromised patients. The correct diagnosis of fungal diseases in these patients following well established treatment will improve the prognosis.     

Brote de histoplasmosis en la provincia de Neuquén,Patagonia Argentina

BackgroundIn Argentina, there are no reports of autochthonous cases of histoplasmosis in the southern regions of the country.AimTo report a histoplasmosis outbreak in Zapala town, Province of Neuquén, Patagonia Argentina.MethodsWe evaluated the clinical and epidemiological characteristics of 5 patients involved in the outbreak. Environmental studies were conducted to determine the source of infection. The genetic profile of Histoplasma capsulatum strains isolated from the index case (IC) were compared with clinical isolates from Argentinean patients not related to the outbreak, using RAPD-PCR with primers 1281-1283.ResultsThe patients were residents of Zapala, and had not visited other geographical areas before. All patients had an influenza-like syndrome, and X-ray revealed disseminated micronodular images throughout the lung parenchyma. The IC needed specific antifungal therapy; the remaining 4 patients had mild symptoms, and did not require therapy. All of them had a good clinical outcome. Strains of H. capsulatum isolated from blood culture and lung biopsy of the IC showed a genetic profile different from other strains analyzed. The presence of the fungus in the environment was demonstrated by the detection of anti-Histoplasma antibodies in BALB/c mice inoculated with soil obtained in a culvert where workers had dug up earth after a landslide.ConclusionsThis outbreak suggests the histoplasmosis endemic area is under the 38° S parallel. Patients from Neuquén, Patagonia Argentina, with compatible symptoms of histoplasmosis should be tested, regardless of their travel or exposure history.     

Histoplasma capsulatum‐induced extracellular DNA trap release in human neutrophils

Neutrophils are leukocytes that are capable of eliminating both intra‐ and extracellular pathogens by mechanisms such as phagocytosis, degranulation, and release of neutrophil extracellular traps (NETs). Histoplasma capsulatum var. capsulatum (H. capsulatum) is a dimorphic fungus with a global distribution that causes histoplasmosis, a disease that is endemic in different geographic areas and is spreading worldwide. The release of NETs has been described as an important host defense mechanism against different fungi; however, there are no reports demonstrating that this process is implicated in neutrophil response to H. capsulatum infection. Therefore, the aim of this work is to investigate whether isolated human neutrophils release NETs in response to H. capsulatum and the potential mechanisms involved, as well as delineate the NETs antifungal activity. Using both confocal fluorescence and scanning electron microscopy techniques, we determined that NETs are released in vitro in response to H. capsulatum via an oxidative mechanism that is downstream of activation of the Syk and Src kinase pathways and is also dependent on CD18. NETs released in response to H. capsulatum yeasts involve the loss of neutrophil viability and are associated with elastase and citrullinated histones, however also can occur in a PAD4 histone citrullination independent pathway. This NETs also presented fungicidal activity against H. capsulatum yeasts. Our findings may contribute to the understanding of how neutrophils recognize and respond as immune effector cells to H. capsulatum, which may lead to better knowledge of histoplasmosis pathophysiology and treatment.     

Algorithm for diagnosis of early Schistosoma haematobium using prodromal signs and symptoms in pre-school age children in an endemic district in Zimbabwe

IntroductionPrompt diagnosis of acute schistosomiasis benefits the individual and provides opportunities for early public health intervention. In endemic areas schistosomiasis is usually contracted during the first 5 years of life, thus it is critical to look at how the infection manifests in this age group. The aim of this study was to describe the prodromal signs and symptoms of early schistosomiasis infection, correlate these with early disease progression and risk score to develop an easy to use clinical algorithm to identify early Schistosoma haematobium infection cases in resource limited settings.MethodologyTwo hundred and four, preschool age children who were lifelong residence of a schistosomiasis endemic district and at high risk of acquiring schistosomiasis were followed up from July 2019 to December 2019, during high transmission season. The children received interval and standard full clinical evaluations and laboratory investigations for schistosomiasis by clinicians blinded from their schistosomiasis infection status. Diagnosis of S. haematobium was by urine filtration collected over three consecutive days. Signs and symptoms of schistosomiasis at first examination visit were compared to follow-up visits. Signs and symptoms common on the last schistosomiasis negative visit (before a subsequent positive) were assigned as early schistosomiasis infection (ESI), after possible alternative causes were ruled out. Logistic regression identified clinical predictors. A model based score was assigned to each predictor to create a risk for every child. An algorithm was created based on the predictor risk scores and validated on a separate cohort of 537 preschool age children.ResultsTwenty-one percent (42) of the participants were negative for S. haematobium infection at baseline but turned positive at follow-up. The ESI participants at the preceding S. haematobium negative visit had the following prodromal signs and symptoms in comparison to non-ESI participants; pruritic rash adjusted odds ratio (AOR) = 21.52 (95% CI 6.38–72.66), fever AOR = 82 (95% CI 10.98–612), abdominal pain AOR = 2.6 (95% CI 1.25–5.43), pallor AOR = 4 (95% CI 1.44–11.12) and a history of facial/body swelling within the previous month AOR = 7.31 (95% CI 3.49–15.33). Furthermore 16% of the ESI group had mild normocytic anaemia, whilst 2% had moderate normocytic anaemia. A risk score model was created using a rounded integer from the relative risks ratios. The diagnostic algorithm created had a sensitivity of 81% and a specificity of 96.9%, Positive predictive value = 87.2% and NPV was 95.2%. The area under the curve for the algorithm was 0.93 (0.90–0.97) in comparison with the urine dipstick AUC = 0.58 (0.48–0.69). There was a similar appearance in the validation cohort as in the derivative cohort.ConclusionThis study demonstrates for the first time prodromal signs and symptoms associated with early S. haematobium infection in pre-school age children. These prodromal signs and symptoms pave way for early intervention and management, thus decreasing the harm of late diagnosis. Our algorithm has the potential to assist in risk-stratifying pre-school age children for early S. haematobium infection. Independent validation of the algorithm on another cohort is needed to assess the utility further.     

Histoplasmosis in the Republic of Congo dominated by African histoplasmosis,Histoplasma capsulatum var. duboisii

The Republic of Congo (RoC) is one of the African countries with the most histoplasmosis cases reported. This review summarizes the current status regarding epidemiology, diagnostic tools, and treatment of histoplasmosis in the RoC. A computerized search was performed from online databases Medline, PubMed, HINARI, and Google Scholar to collect literature on histoplasmosis in the RoC. We found 57 cases of histoplasmosis diagnosed between 1954 and 2019, corresponding to an incidence rate of 1–3 cases each year without significant impact of the AIDS epidemic in the country. Of the 57 cases, 54 (94.7%) were cases of Histoplasma capsulatum var. duboisii (Hcd) infection, African histoplasmosis. Three cases (5.3%) of Histoplasma capsulatum var. capsulatum infection were recorded, but all were acquired outside in the RoC. The patients’ ages ranged between 13 months to 60 years. An equal number of cases were observed in adults in the third or fourth decades (n = 14; 24.6%) and in children aged ≤15 years. Skin lesions (46.3%), lymph nodes (37%), and bone lesions (26%) were the most frequent clinical presentations. Most diagnoses were based on histopathology and distinctive large yeast forms seen in tissue. Amphotericin B (AmB) was first line therapy in 65% of the cases and itraconazole (25%) for maintenance therapy. The occurrence of African histoplasmosis in apparently normal children raises the possibility that African histoplasmosis is linked to environmental fungal exposure.     

Histoplasma capsulatum Recovery from the Urine and a Short Review of Genitourinary Histoplasmosis

Although virtually any organ can be involved in disseminated histoplasmosis, the recovery of Histoplasma capsulatum from the urine is a rare finding. Here we describe that a renal transplant recipient had H. capsulatum recovered from urinary sediment. The organism was also recovered from urine cultures. The potential implications of this finding are discussed, and the literature on genitourinary histoplasmosis is reviewed.     

Chronic Cavitary Histoplasmosis of the Lung

Four main clinical types of disease result from infection by the fungus Histoplasma capsulatum: (1) the primary complex; (2) acute pulmonary histoplasmosis; (3) chronic cavitary pulmonary histoplasmosis; (4) disseminated systemic histoplasmosis.Chronic cavitary histoplasmosis of the lung is indistinguishable clinically and radiographically from pulmonary tuberculosis. In this disease, however, the histoplasmin skin test and the histoplasmin complement fixation test are positive in more than 80% of cases and sputum cultures are usually positive for Histoplasma capsulatum. The mortality rate of the chronic cavitary type is greater than 30%. The antibiotic, amphotericin B, is the most effective drug in treatment. If surgical resection of the cavitary lesion is feasible, under amphotericin coverage, this is the treatment of choice.During the past year, two patients with chronic cavitary histoplasmosis illustrating the aforementioned features were diagnosed at the Toronto Hospital for Tuberculosis.     

Multiple opportunistic fungal infections in an individual with severe HIV disease: A case report

BackgroundFungal infections have been commonly diagnosed in individuals with advanced HIV disease. Cryptococcosis, pneumocystosis, and histoplasmosis are the most frequent systemic mycoses in people suffering from HIV/AIDS.Case reportWe report a case of multiple fungal infections in an advanced AIDS-patient. A 33-year-old HIV-positive man from Brazil was hospitalized due to diarrhea, dyspnea, emaciation, hypoxemia, extensive oral thrush, and a CD4+ T lymphocyte count of 20 cells/mm³. Honeycombed-structures consistent with Pneumocystis jirovecii were observed by direct immunofluorescence in induced sputum. Cryptococcus neoformans was recovered from respiratory secretion and cerebrospinal fluid cultures. Histopathology of the bone marrow also revealed the presence of Histoplasma capsulatum. Molecular assays were performed in a sputum sample. Nested-PCR confirmed the presence of P. jirovecii and H. capsulatum; qPCR multiplex was positive for C. neoformans and H. capsulatum. With the treatment of antifungal drugs the patient progressed satisfactorily.ConclusionsThe diagnosis of several systemic mycoses demonstrates the vulnerability of advanced AIDS-patients. Thus, the detection of AIDS cases in the early stages of infection is necessary for a prompt and adequate introduction of HAART therapy, and the use of prophylaxis to control opportunistic infections.     

Detection of Environmental Sources of Histoplasma capsulatum in Chiang Mai, Thailand, by Nested PCR

Histoplasmosis is a systemic mycosis caused by inhaling spores of Histoplasma capsulatum, a dimorphic fungus. This fungus grows in soil contaminated with bat and avian excreta. Each year, patients with disseminated histoplasmosis have been diagnosed in Chiang Mai, northern Thailand. No published information is currently available on the environmental sources of this fungus in Chiang Mai or anywhere else in Thailand. The aim of this study was to detect H. capsulatum in soil samples contaminated with bat guano and avian droppings by nested PCR. Two hundred and sixty-five samples were collected from the following three sources: soil contaminated with bat guano, 88 samples; soil contaminated with bird droppings, 86 samples; and soil contaminated with chicken droppings, 91 samples. Genomic DNA was directly extracted from each sample, and H. capsulatum was detected by nested PCR using a primer set specific to a gene encoding 100-kDa-like protein (HcI, HcII and HcIII, HcIV). Histoplasma capsulatum was detected in seven of 88 soil samples contaminated with bat guano, one of 21 soil samples contaminated with pigeon droppings and 10 of 91 soil samples contaminated with chicken droppings. The results indicate the possibility of the association of bat guano and chicken droppings with H. capsulatum in this area of Thailand.     

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

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

Taking care of a diarrhea epidemic in an urban hospital in Bangladesh: Appraisal of putative causes,presentation, management,and deaths averted

BackgroundIn April 2018, a diarrhea epidemic broke out in Dhaka city and adjoining areas, which continued through May. The Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), a dedicated diarrheal disease hospital, had a large upsurge in patient visits during the epidemic. An enhanced understanding of the epidemiology of this epidemic may help health-related professionals better prepare for such events in the future. This study examined the microbial etiology and non-pathogen factors associated with diarrhea during the epidemic. The study also evaluated the patients’ presentation and clinical course and estimated the potential mortality averted by treating patients during the epidemic.Methodology/Principal findingsData from the patients who were treated at Dhaka Hospital during the diarrhea epidemic between April 2 and May 12, 2018 and were enrolled into the Diarrheal Disease Surveillance System (DDSS) at icddr,b were compared with the DDSS-enrolled patients treated during the seasonally-matched periods in the flanking years using logistic regression. icddr,b Dhaka Hospital treated 29,212 diarrheal patients during the 2018 epidemic period (and 25,950 patients per comparison period on average). Vibrio cholerae was the most common pathogen isolated (7,946 patients; 27%) and associated with diarrhea during the epidemic (adjusted odds ratio [AOR] 1.5, 95% CI: 1.1–2.0). The interaction of Vibrio cholerae with ETEC (AOR 2.7, 95% CI: 1.3–5.9) or Campylobacter (AOR 2.4, 95% CI: 1.1–5.1) was associated with further increased odds of diarrhea during the epidemic. In children under five years old, rotavirus was the most common pathogen (2,029 patients; 26%). Those who were adolescents (AOR 2.0, 95% CI: 1.3–3.1) and young adults (AOR 1.9, 95% CI: 1.4–2.5) compared to children younger than five years, resided within a 10 km radius of Dhaka Hospital (AOR 1.6, 95% CI: 1.1–2.2) compared to those living outside 20 km, borrowed money or relied on aid to pay for the transport to the hospital (AOR 1.6, 95% CI: 1.2–2.0), used tap water (AOR 1.8, 95% CI: 1.4–2.4) for drinking compared to tubewell water, and disposed of the solid waste directly outside the house (AOR 4.0, 95% CI: 2.7–5.9) were more likely to present with diarrhea during the epidemic. During the epidemic, patients were more likely to present with severe dehydration (odds ratio [OR] 1.6, 95% CI: 1.3–2.0) and require inpatient admission (OR 2.5, 95% CI: 1.9–3.3), intravenous rehydration (OR 1.7, 95% CI: 1.4–2.1), and antibiotics (OR 2.2, 95% CI: 1.8–2.7). The in-hospital case fatality rate was low (13 patients; 0.04%), and the hospital averted between 12,523 and 17,265 deaths during the epidemic.Conclusions/SignificanceVibrio cholerae played the primary role in the 2018 diarrhea epidemic in Dhaka. Campylobacter, enterotoxigenic Escherichia coli, and rotavirus had a secondary role. Adolescents and adults, residents of the metropolitan area, and those who were relatively poor and lacked safe water, sanitation, and hygiene (WASH) practices comprised the most vulnerable groups. Despite the increased disease severity during the epidemic, the case fatality rate was less than 0.1%. icddr,b Dhaka Hospital saved as many as 17,265 lives during the epidemic.     

Perforation of the Nasal Septum as the First Sign of Histoplasmosis Associated with AIDS and Review of Published Literature

Disseminated histoplasmosis in South America is associated with AIDS in 70–90 % of cases. It is visceral and cutaneous, compromising the oral, pharynx, and laryngeal mucous membranes. The involvement of the nasal mucosa is unusual. Two patients with perforation of the nasal septum as the only sign of their disease were clinically and histopathologically diagnosed as leishmaniasis. The revision of the biopsies and the culture of nasal discharge secretions showed that the pathogens seen were not amastigotes but Histoplasma capsulatum. Other mycotic lesions were not detected, nor there was history of cutaneous leishmaniasis. The leishmanin skin test, available only for the male patient, was negative. The PCR and immunofluorescence antibody titers for Leishmania were negative in both patients. They were HIV positive; in the male, his CD4+ T cell count was 60/mm³ and in the female 133/mm³. The nasal ulcer was the only manifestation of histoplasmosis and the first of AIDS in both patients. The male patient recovered with amphotericin B and itraconazole treatment. The female has improved with itraconazole. Both patients received antiretroviral treatment. Nasal mucous membrane ulcers should include histoplasmosis among the differential diagnosis. In conclusion, two patients had perforation of their nasal septum as the only manifestation of histoplasmosis, a diagnosis confirmed by nasal mucosa biopsy and by culture of H. capsulatum, findings which demonstrated that both patients had AIDS.     

Second Case of Histoplasmosis in a Captive Mara (<Emphasis Type="Italic">Dolichotis patagonum</Emphasis>): Pathological Findings

A second case of histoplasmosis in a captive mara (Dolichotis patagonum) from a colony at the wildlife park Africam Safari, Puebla, Mexico, is described, and the mara died with disseminated clinical form of the disease, affecting mostly the large intestine and adrenal. The pathological findings of this case 2 revealed severe granulomatous typhlocolitis and moderate granulomatous gastrohepatic lymphadenitis with numerous yeast-like cells, 2–4 μm in diameter, with a clear halo surrounding them inside the cytoplasm of macrophages, suggesting the parasitic form of Histoplasma capsulatum. Adrenocortical cells had abundant similar microorganisms in their cytoplasm without any associated lesion. Gomori’s methenamine silver and periodic acid Schiff stained positively these microorganisms. Immunohistochemistry, using a rabbit anti-H. capsulatum serum, and transmission electron microscopy supported the diagnosis of H. capsulatum infection.     

Two Specific Strains of <Emphasis Type="Italic">Histoplasma capsulatum</Emphasis> causing Mucocutaneous Manifestations of Histoplasmosis: Preliminary Analysis of a Frequent Manifestation of Histoplasmosis in Southern Brazil

Objectives  Skin lesions, uncommon in US cases (<10%), occur in 38–85% of cases reported from Latin America. Although these differences may reflect reporting bias, delayed diagnosis, or differences in host immune response among different ethnic groups, they also could result from genetic differences changing the pathobiology of the organism. It is possible that genetic differences among strains of H. capsulatum may influence the pathogenesis and clinical manifestations of histoplasmosis. Methods  We examined the clinical features of patients with mucocutaneous manifestations of histoplasmosis and performed genetic analysis based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes of H. capsulatum isolates of patients. Two pairs of PCR primers were designed to develop and amplify the ITS regions of H. capsulatum, 5′-TACCCGGCCACCCTTGTCTA-3′ and 5′-AGCGGGTGGCAAAGCCC-3′. These primers were based on the ITS sequence of Ajellomyces capsulatus, the ascomycetous teleomorph form of H. capsulatum, deposited in the GenBank (accession number U18363). Eight patients attending a tertiary-care hospital in southern Brazil were enrolled into the study. All case patients had skin cultures growing H. capsulatum at the mycology laboratory. Results  Six of eight (75%) patients were HIV-positive and presented involvement of multiples organs by H. capsulatum. Two HIV-negative patients did not present evidence of involvement of other organs besides mucosa and skin. ITS sequencing of a DNA H. capsulatum fragment of 485-bp from isolates of 8 patients revealed two distinct strains. The 2 distinct fragments (Hc1, Hc2) differed from each other at 7 positions in the ITS regions. They were identical to strains of H. capsulatum isolated in patients from Colombia and Argentina, but different from strains isolated in US. Hc1 and Hc2 were isolated in 5 patients and 3 patients, respectively, with mucocutaneous manifestations of histoplasmosis. Both Hc1 and Hc2 strains were isolated in HIV-infected and non-HIV-infected patients. Conclusions  Mucocutaneous manifestations of histoplasmosis, which are frequently seen in Brazilian patients were caused by 2 specific strains in our institution. Those strains have been isolated in patients with these particular clinical features of histoplasmosis in Latin America. Our study suggests that unique pathogenic characteristics among the Latin American species of H. capsulatum might explain its increased dermatotropism.     

HIV-Associated Histoplasmosis Early Mortality and Incidence Trends: From Neglect to Priority

Background

Histoplasmosis 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.

Methods

A 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.

Results

There 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.

Conclusion

From 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.