Aldo Mazzoni

Histoplasmosis capsulati and duboisii in Europe: The impact of the HIV pandemic, travel and immigration

The present report describes a fatal case of imported AIDS-related disseminated histoplasmosis capsulati infection associated with multiple coexisting infections, diagnosed with cultural recovery ofHistoplasma capsulation var.capsulatum with a commercial radiometricMycobacterium medium. The epidemiological and clinical features of histoplasmosis capsulati and duboisii in Europe are reviewed by examining also 69 documented cases ofHistoplasma capsulatum var.capsulatum infection (25 in AIDS patients) and 17 cases ofHistoplasma capsulatum var.duboisii infection (3 in HIV-infected patients), described since 1980. This draws special attention to the role played during recent years by the emergence of the HIV pandemic and the progressive intensification of travel and immigration as risk factors for this disease in our continent. AIDS patients, who are prone to multiple concurrent opportunistic infections which may share clinical and laboratory features with each other and with other HIV-associated diseases, represent the most relevant current group at risk for severe disseminated histoplasmosis, which may come to medical attention far from their place of origin.

Survey of soils for human pathogenic fungi from the Emilia-Romagna region of Italy.

A group of 166 soil samples collected in the Emilia-Romagna region of Italy from avian and chiropteran habitats was examined for the presence of keratinophilic fungi. One hundred forty-four isolates, classified among 14 genera, were obtained. The majority of the fungi were members of the family Gymnoascaceae. The significance of these findings was discussed.

Histoplasmosis in Europe.

After reviewing the reports ofHistoplasma capsulatum in man, animal and soil, and the results of histoplasmin sensitivity tests in Europe, we have concluded that autochthonous histoplasmosis is present but rare in Europe.

Histoplasma capsulatum var. capsulatum occurring in an HIV‐positive Ghanaian immigrant to Italy

Histoplasmosis, which is highly endemic in the United States, is rare in Europe, usually imported but sometimes autochthonous. In Africa, histoplasmosis capsulati coexists with “African histoplasmosis”, a characteristic skin infection caused by H. capsulatum var. duboisii. Histoplamosis due to H. capsulatum is one of the 12 secondary infections listed in the surveillance definitions of AIDS. We report the case of a 36‐year‐old black man with acquired immunodeficiency syndrome (AIDS) who was living in Italy but originally came from Ghana. Histoplasmosis was disseminated with fever and cutaneous manifestations. The diagnosis was demonstrated morphologically based on the presence of yeast, observed by light microscopy, in skin lesions and by identification of H. capsulatum var. capsulatum DNA by nested PCR from a paraffin sample. No clinical reports of histoplamosis capsulati in Ghana have been published until now. The present case stresses the role of immigration of subjects from outside Europe who have been infected in their native country.

Histoplasmosis in Italy. I. Isolation of Histoplasma capsulatum from dogs in the province of Bologna

The peribronchial lymph nodes of 150 dogs from the province of Bologna were cultured for human pathogenic fungi. Hosplasma capsulatum was recovered from 2 dogs. This finding, coupled with an earlier isolation of H. capsulatum from a chicken yard soil sample from the same region, indicates that an endemic area for H. capsulatum exists in northern Italy.

Primary lymph node invasive aspergillosis

A case of apparently primary lymph node granulomatous aspergillosis is described. A review of the so-called primary aspergillosis cases since 1977 shows that granulomatous instead of exudative inflammation patterns have been observed in histological sections only when neither major nor minor predisposing factors have been detected in the clinical history of the patients. A possible pathogenetic role of selectively impaired cell-mediated immune response in these cases is hypothesized. Flucytosine treatment is indicated in a few selected cases of deep aspergillosis. Ein Fall von offensichtlich primärer granulomatöser Aspergillose der Lymphknoten wird beschrieben. Eine retrospektive Analyse der Fälle von sogenannter primärer Aspergillose, beginnend im Jahr 1977, zeigt, daß in den histologischen Schnitten vor allem granulomatöse anstelle von exsudativen Infiltraten beobachtet werden konnten. Dieses trifft besonders dann zu, wenn weder bedeutende noch geringfügige prädisponierende Faktoren in der Anamnese der Patienten entdeckt werden konnten. Eine mögliche pathogenetische Rolle wird in diesen Fällen der selektiven Beeinträchtigung der zellvermittelten Immunantwort zugesprochen. Die Behandlung mit Flucytosin ist in wenigen ausgewählten Fällen von tiefer Aspergillose indiziert.SummaryA case of apparently primary lymph node granulomatous aspergillosis is described. A review of the so-called primary aspergillosis cases since 1977 shows that granulomatous instead of exudative inflammation patterns have been observed in histological sections only when neither major nor minor predisposing factors have been detected in the clinical history of the patients. A possible pathogenetic role of selectively impaired cell-mediated immune response in these cases is hypothesized. Flucytosine treatment is indicated in a few selected cases of deep aspergillosis.ZusammenfassungEin Fall von offensichtlich primärer granulomatöser Aspergillose der Lymphknoten wird beschrieben. Eine retrospektive Analyse der Fälle von sogenannter primärer Aspergillose, beginnend im Jahr 1977, zeigt, daß in den histologischen Schnitten vor allem granulomatöse anstelle von exsudativen Infiltraten beobachtet werden konnten. Dieses trifft besonders dann zu, wenn weder bedeutende noch geringfügige prädisponierende Faktoren in der Anamnese der Patienten entdeckt werden konnten. Eine mögliche pathogenetische Rolle wird in diesen Fällen der selektiven Beeinträchtigung der zellvermittelten Immunantwort zugesprochen. Die Behandlung mit Flucytosin ist in wenigen ausgewählten Fällen von tiefer Aspergillose indiziert.

SIMULTANEOUS OCCURRENCE OF VISCERAL LEISHMANIASIS AND DISSEMINATED HISTOPLASMOSIS IN AN ITALIAN PATIENT WITH HIV INFECTION

Both disseminated histoplasmosis and visceral leishmaniasis are being recognised with increasing frequency as opportunistic infections in HIV-infected patients, predominantly in their respective endemic areas. In fact, AIDS-related disseminated Histoplasma capsulaturn infection is relatively common in highly endemic areas of Northern and Central America and Africa [1] and is rarely observed in non-endemic regions such as Europe (where only a few isolated cases have been seen [2-6]), whereas HIV-associated visceral leishmaniasis has been reported primarily from several hypo-endemic regions, such as Spain, Southern France and Italy [7-9]. A case of fatal simultaneous infection by H. capsulatum and Leishmania is described in an Italian HIV-infected patient. Four weeks after coming back from a trip in Mexico and Central America, a 29-year-old ex-IV drug abuser presented with fever, severe weight loss, arthromyalgia, cough and dyspnoea. He previously received zidovudine and aerosolised pentamidine for primary prophylaxis of Pneumocystis carinii infection; chloroquine antimalarial chemoprophylaxis had been carried out correctly, during and after the recent journey. Clinical examination showed liver and spleen enlargement, polyadenopathy and oropharyngeal candidiasis, while a chest radiograph revealed bilateral reticulonodular infiltrates. Laboratory findings showed a severe immunosuppression (total leukocyte count 1,990/mm 3, CD4+ lymphocytes 48/ram 3) and anaemia, thrombocytopenia, hypergammaglobulinaemia and elevation of serum AST-ALT, alkaline phosphatase, gamma-GT and LDH. When blood cultures yielded Staphylococcus epidermidis and acid-fast bacilli were recovered from bronchoalveolar lavage, an antibiotic treatment (ceftazidime plus netilmicin) and a four-drug tuberculostatic regimen were started together with fluconazote for oral candidiasis, without any improvement of the clinical picture. Visualisation of the typical Leishmania amastigotes in Giemsa stain of smears of bone marrow aspirates established a diagnosis of visceral leishmaniasis (Figure 1A and Figure 1C). An initial treatment with meglumine antimoniate (20 mg/Kg/day) associated with allopurinol was replaced by pentamidine (4 mg/Kg/day) after 9 days because of the occurrence of adverse events (cardiotoxicity and hypotension). In spite of treatment, clinical conditions progressively worsened, showing hyperpyrexia, impressive hepatosplenomegaly, severe anaemia and thrombocytopenia, leading to death 5 weeks after admission with a septic shock-like syndrome characterised by hypotension, multi-organ failure and disseminated intravascular coagulation. Relatives refused necropsy examination. Two weeks after the patients death, H. capsulatum was recovered from five consecutive blood specimens cultured for Mycobacterium spp. on Middlebrook 7H9 Base radiometric medium (MB Check, Hoffmann-La Roche, Basel, Switzerland) after an overall 20-day incubation. Subcultures made on brain-heart infusion agar at 37°C (yeast phase), and Saboraud dextrose agar at room temperature (reversion into the mycelial phase, with demonstration of septate hyphae and characteristic large tuberculate macroconidia), confirmed the diagnosis. A successive review of bone marrow smears stained with periodic acid-Schiff led to the identification of a large amount of intracellular fungal organisms, together with Leishmania amastigotes (Figure 1 B), while Leishmania serology made with an indirect immunofluorescence assay on three consecutive serum samFigure 1A: Giemsa stain of a bone marrow specimen showing Leishmania amastigotes as 1-2 txm intracytoplasmatic bodies (thin arrow), together with intracellular organisms consistent with the yeast form of Histoplasma capsulatum (thick arrow).

Progressive Intractable Actinomycosis in Patients with AIDS

Two rare cases of progressive oropharyngeal actinomycosis, characterized by a subacute and invasive course despite seemingly appropriate antibiotic and surgical treatment, have been observed in patients with AIDS. A brief review of previously reported cases of actinomycosis in HIV-infected patients is presented. Clinical, diagnostic and therapeutic problems dealing with actinomycosis in the immunocompromised host are discussed.

Histoplasmosis capsulati in Italy: Autochthonous or imported?

Reports of a few apparently autochtonous cases of human histoplasmosis and results of epidemiological research suggested the autochthonous presence of the disease in Italy. Identifying two new histologically documented cases of Italian patients, who had never been abroad, and, the positive results of a histoplasmin reactivity survey carried out in the Province of Cremona, Italy confirmed this possibility.

AIDS-related visceral aspergillosis: an underdiagnosed disease during life?: AIDS-assoziierte tieflokalisierte Aspergillose: Bei Lebzeiten nicht immer erkannt?

Summary. Five out of nine consecutive patients with HIV‐related visceral aspergillosis observed by us since 1984 were diagnosed only at necropsy examination. The histopathological features of these five patients [two with isolated pneumonia, one with central nervous system (CNS) involvement, one with brain abscess and respiratory disease and one with pulmonary, pleural and kidney infection] have been evaluated according to epidemiological, clinical and radiological features. On the basis of our experience, lifethreatening aspergillosis, which is often misdiagnosed or missed in the setting of HIV infection and AIDS, should be suspected in patients with far‐advanced underlying disease and unexplained signs and symptoms, even in the absence of some presumed risk factors (i.e. neutropenia and prior steroid treatment). Plain chest radiography and bronchoscopy with broncholaveolar lavage may fail to reveal respiratory disease, CNS aspergillosis is not necessarily associated with suggestive neuroradiological features and disseminated disease may present with multiorgan failure. The unfavorable outcome of this emerging AIDS complication can be improved only by earlier diagnosis based on invasive techniques and appropraite and timely treatment.