Pulmonary cryptococcosis: A rare but emerging disease

Pulmonary cryptococcosis occurs primarily in immunocompromised hosts as an isolated infection or as a precursor to disseminated disease. Recent studies indicate that patients with isolated pulmonary cryptococcosis may be asymptomatic or, if symptomatic, will often have very low serum cryptococcal antigen, distinguishing them from patients with disseminated disease. Amphotericin B plus flucytosine is the initial treatment for disseminated cryptococcosis or severe symptomatic pulmonary cryptococcosis, followed by fluconazole once symptoms have improved. Fluconazole is recommended for asymptomatic or mild disease. Targeted immunotherapies and vaccines are being studied and offer exciting new prevention and treatment strategies.     

Opportunistic invasive mycoses in AIDS. An autopsy study of 211 cases.

The opportunistic mycoses are an important cause of morbidity-mortality among patients with severe immunosuppression provoked by HIV. We present a study of 211 serial autopsies of patients with HIV/AIDS infection carried out by our service in a period of 10 years, observing frequency of invasive mycoses of the 44.1%. Pneumocystis carinii infection was the most frequent (32%) with a prevalence of lung affection. Candidiasis follows it in order of frequency with 31.1%, predominantly the oropharyngeal manifestation. Systemic or cerebromeningeal cryptococcosis were serious and common disorder (29%). Diseminated histoplasmosis occurred in 9.6% and in three cases (3.2%) pulmonary aspergillosis was diagnosed as a postmortem discovery in cavity lesions. In our series, other less common HIV-associated were not identified.     

Epidemiology of Invasive Fungal Infections in Patients with Acquired Immunodeficiency Syndrome at a Reference Hospital for Infectious Diseases in Brazil

Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20–25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.     

Innate host defenses against <Emphasis Type="Italic">Cryptococcus neoformans</Emphasis>

Cryptococcus neoformans, the predominant etiological agent of cryptococcosis, can cause life-threatening infections of the central nervous system in immunocompromised and immunocompetent individuals. Cryptococcal meningoencephalitis is the most common disseminated fungal infection in AIDS patients, and remains the third most common invasive fungal infection among organ transplant recipients. The administration of highly active antiretroviral therapy (HAART) has resulted in a decrease in the number of cases of AIDS-related cryptococcosis in developed countries, but in developing countries where HAART is not readily available, Cryptococcus is still a major concern. Therefore, there is an urgent need for the development of novel therapies and/or vaccines to combat cryptococcosis. Understanding the protective immune responses against Cryptococcus is critical for development of vaccines and immunotherapies to combat cryptococcosis. Consequently, this review focuses on our current knowledge of protective immune responses to C. neoformans, with an emphasis on innate immune responses.     

Cryptococcosis in China (1985–2010): Review of Cases from Chinese Database

Background

Cryptococcosis is a potential fatal disease, especially in immunocompromised patients. In China, the profile of cryptococcosis is unclear. Therefore, we summarize the epidemiology and therapy of cryptococcosis in china.

Methods

All cases reports about cryptococcosis in China were collected from CBMdisk database (China Biology and Medicine data disc) with key words of cryptococcosis, or cryptococcal infection, or cryptococcus, and case. The features of the cryptococcosis were retrospectively analyzed.

Results

There were 1,032 reports about cryptococcosis, including 8,769 cases. Among them, there were 16% patient with AIDS/HIV, and 17% ones without underlying diseases. There were 2,371 cases of CNS infection. Among them of 2,068 cases, the treatment protocols and outcome were clearly described. The percentages of patients who received intrathecal treatment of amphotericin B(AmB), AmB?+?5-FC(5-fluorocytosine), AmB?+?FCZ(fluconazole), and AmB?+?5-FU?+?FCZ in each medication group were 10, 43, 53, and 33%, respectively. The mortalities were significantly lower in the AmB, Amb?+?5-FC, AmB?+?FCZ intrathecal treatment groups compared with their non-intrathecal treatment controls (6% vs. 23%, 25% vs. 35%, 20% vs. 30%, respectively, P?P?>?0.05).

Conclusion

The Chinese cryptococcosis had its own special clinical features, such as more patients without identifiable underlying diseases. Intrathecal injection of amphotericin B was effective treatment method for cryptococcal CNS infection in China.     

Asymptomatic pulmonary cryptococcosis diagnosed on fine needle aspiration cytology. A case report

BACKGROUND: Cryptococcosis can be a life-threatening mycosis in immunocompromised patients. However, it has a somewhat better prognosis in immunocompetent hosts. AIDS has led to an increase in the incidence of the disease. Clinically, the lesions can be confused easily with malignancy. CASE: A 25-year-old, asymptomatic male presented for a routine health check-up. The chest radiograph showed a subpleural left apical area of consolidation, suspicious for either a neoplasm or infection. Fine needle aspiration cytology (FNAC) revealed a granulomatous lesion with refractile yeast forms of Cryptococcus, both within the multinucleate giant cells and extracellularly. This was subsequently confirmed by culture and histology. CONCLUSION: The cytomorphology of cryptococcosis is characteristic, and FNAC is a useful modality for diagnosing the infection in asymptomatic patients but needs a high index of suspicion, especially in nonimmunocompromised patients.     

Epidemiological Profile of Cryptococcal Meningitis Patients in Rio Grande do Sul,Brazil

Cryptococcosis is a major opportunistic mycosis which has meningitis as its most frequent clinical presentation and can be fatal in the absence of antifungal therapy. The aetiological agents are Cryptococcus neoformans, which affects mainly immunocompromised subjects, and C. gattii, the aetiologic agent for cryptococcosis in healthy individuals. A recent outbreak of cryptococcosis on Vancouver Island, Canada, raised the level of concern about the epidemiology of this disease. In Brazil, between 1980 and 2002, six per cent of AIDS patients had cryptococcosis in course at the time of diagnosis. To identify the profile of cryptococcal meningitis patients in Rio Grande do Sul (RS), Brazil, a retroactive study was realized using data from patients registered at Laboratório Central de Saúde Pública IPB-LACEN/RS from 2000 to 2005. Most of the patients were men (77.12%), Caucasian (83.5%), median age between thirty and thirty-nine years old (46.24%) and HIV positive (95%).     

Pulmonary nodules: An unusual onset of HIV infection belatedly diagnosed

BackgroundCryptococcosis is a generally systemic and potentially lethal fungal infection. Although HIV infection is a predisposing condition, especially if the CD₄₊ lymphocyte count is less than 100 cells/mm³, other forms of immunosuppression may be associated with this opportunistic fungal condition, such as prolonged steroid therapy or solid organ transplantation. Pulmonary presentation must be included in the differential diagnosis of pneumonia or pulmonary neoplasia in the immunosuppressed patient.Case reportWe report a case of pulmonary cryptococcosis in a non-diagnosed HIV patient. In a 44 year-old male suffering from dyspnea and chest pain the image of a pulmonary nodule was observed in a radiological finding. In the histopathological study, intracellular structures suggestive of fungal conidia, and morphologically compatible with Cryptococcus, were observed. HIV serology and cryptococcal antigen detection in serum were requested, given the possibility of cryptococcosis. Cryptococcus neoformans var. grubii was isolated from the culture of the pulmonary biopsy. The patient was finally diagnosed with pulmonary cryptococcosis and HIV-1 infection. With a proper antifungal treatment the patient evolved satisfactorily.ConclusionsThe best strategy to avoid opportunistic infections such as cryptococcosis in HIV-infected patients consists of an early diagnosis and a highly active antiretroviral treatment. In our case, the diagnosis of a pulmonary infection by C. neoformans var. grubii allowed a late diagnosis of HIV-1 infection.     

Pulmonary mucormycosis diagnosed by fine needle aspiration cytology. A case report

BACKGROUND: The usefulness of fine needle aspiration cytology (FNAC) in the diagnosis of lung lesions is well documented. Fungal lesions are among nonneoplastic lesions of the lung in which FNAC has proven a useful technique in both immunocompromised and immunocompetent patients. These include cryptococcosis, aspergillosis, histoplasmosis and coccidiodomycosis. Pulmonary mucormycosis, an aggressive fungal infection, is rarely diagnosed on FNAC. We report a case of isolated pulmonary mucormycosis diagnosed on FNAC. CASE: A 62-year-old renal transplant recipient with diabetes mellitus and hypertension, asymptomatic for four months, presented with tachypnea, generalized malaise and weakness. Radiologic studies showed an enlarging, cavitating lesion in the right lung. Computed tomography-guided fine needle aspiration performed on the lung lesion showed fungal profiles with broad, ribbonlike, aseptate hyphae with right-angled branching consistent with the Zygomycetes class of fungi, which includes Rhizopus and Mucor species. Fungal cultures confirmed the presence of Rhizopus. The patient underwent right pneumonectomy, was placed on liposomal amphotericin B therapy and discharged with good pulmonary status and stable kidney function. CONCLUSION: FNAC is a useful technique in the diagnosis of pulmonary mucormycosis.     

Clinical, epidemiological and outcome features of patients with cryptococcosis in Uberaba, Minas Gerais, Brazil

Nearly one million of cryptococcosis cases occur yearly around the world, involving mainly HIV-infected patients who are not receiving antiretroviral therapy (ART) or present poor adherence. This study aims to evaluate epidemiological, clinical and outcome aspects of patients with cryptococcosis from 1998-2010. Patients were prospectively recruited, and their medical and laboratory records were reviewed. A total of 131 cases were included, and of these, 119 (90.83%) had AIDS, 4 received a renal transplant, 2 presented systemic lupus erythematosus and 6 (4.6%) were apparently immunocompetent. Ninety-one (69.46%) were men, and the median age was 38.7?years. Cryptococcal meningitis (CM) was diagnosed in 103 (78.62%), whereas 28 (21.38%) had cryptococcal infection in other sites. Of patients with CM, 94 (91.26%) had AIDS being cryptococcosis the first defining illness in 61 (64.9%), while 37 (60.65%) of them presented simultaneously both diagnosis. Headache, altered mental status, papilledema and seizures at admission were significatively associated with a poor outcome. Of 163 different isolates, 155 (95.09%) were Cryptococcus neoformans and eight (4.88%) Cryptococcus gattii. Antifungal therapy was warranted in 8 (87.4%) patients with CM, but 46 (51.1%) died during the first days or weeks. Of 28 patients without CM, 21?(75%) received treatment, but 6 (28.6%) died. The poor outcome among this case series was similar to that reported from other developing countries, but it is paradoxal in Brazil where the ART is at free disposal in the public health services. Despite, at least 60-70% of patients present advanced immunosuppression when they receive the AIDS diagnosis.     

Penicillium marneffei Infection in Immunocompromised Host

Penicillium marneffei (PM) was first described in 1973, causing human infection in a patient with Hodgkin Lymphoma. In the HIV/AIDS epidemic, it has been described as one of the important opportunistic infection following tuberculosis and cryptococcosis in endemic region of Southeast Asia and Southern China. Immunocompromised patients acquire penicilliosis through inhalation of conidia, resulting in disseminated disease characterized by prolonged fever, pancytopenia, hepatosplenomegaly, and classic cutaneous presentation of umbilicated papular eruption. Nowadays, rare manifestations such as fungemia, pneumonia, enterocolitis, genital ulcers, oral ulcer, and central nervous system infection have been reported. Over the past decade, molecular and genomic studies have revealed more knowledge of PM, and vaccines are under development. Modern era PM has become a serious threat in immunocompromised travelers, rather than HIV/AIDS patient in the endemic area, who receive an effective prophylaxis strategy along with the highly active antiretroviral therapy (HAART) initiation.     

Yeast glucan of Pneumocystis carinii cyst wall: an excellent target for chemotherapy.

Pneumocystis pneumonia is the most serious opportunistic infection in immunocompromised patients, particularly those with AIDS. Approved therapy is limited to pentamidine and inhibitors of folic acid synthesis, but these drugs show a high rate of adverse reactions in AIDS patients emphasizing the urgent need for additional effective therapies. Progress has, however, been hindered by lack of knowledge about this parasite's cellular characteristics. Previously we reported that beta (1,3)glucan is a major component of the Pneumocystis carinii cyst wall. This study shows that administration of aculeacin A, an inhibitor of beta (1,3)glucan biosynthesis, affects cyst wall formation, inhibits cyst maturation, and prevents severe pneumonia in steroid-treated rats. Thus this study not only demonstrates that beta (1,3)glucan is indispensable for growth of the parasite in rats, but suggests a new therapeutic strategy for human pneumocystosis.     

Tongue lesion due to Cryptococcus neoformans as the first finding in an HIV-positive patient

BackgroundCryptococcosis is a severe universally distributed mycosis which mainly affects immunocompromised hosts. This mycosis is caused by yeasts of two species complex of the genus Cryptococcus: Cryptococcus neoformans and Cryptococcus gattii. Meningeal cryptococcosis is the most frequent clinical presentation of this disseminated mycosis. The oral mucosa involvement is extremely unusual.Case reportWe present a case of cryptococcosis with an unusual clinical form. The patient was assisted because she had an ulcerated lesion on the lingual mucosa. Encapsulated yeasts compatible with Cryptococcus were found in microscopic exams of wet preparations from lingual ulcer clinical samples obtained for cytodiagnosis and mycological studies. Cryptococcus neoformans (C. neoformans var. grubii VNI) was isolated in culture. This patient did not know her condition of HIV seropositive before the appearance of the tongue lesion.ConclusionsThe involvement of the oral mucosa is uncommon in this fungal infection, but is important to include it in the differential diagnosis in HIV positive patients.     

Crystals occurring in pulmonary cytology specimens. Association with Aspergillus infection

Birefringent needlelike crystals in rosette or wheat-sheaf-like arrangements were found in pulmonary cytology specimens from 11 of 65 patients who had either sputum cultures positive for Aspergillus or histologically confirmed pulmonary aspergilloma. No crystals were found in specimens from 60 control patients with and without known fungal disease. The crystals were most often associated with A. niger infection (45.4%), followed by A. flavus (16%). Crystals were also observed in one case of A. fumigatus infection and in one case in which the species was not determined. In two cases, crystals were found more than one year before sputum cultures became positive; in one of these patients, a fungus ball was not identified by X ray until five years after the first appearance of the crystals in the sputum. Sixty-four percent of the patients with crystals also showed moderate to severe cytologic atypia. The crystals are thought to be calcium oxalate. We conclude that the presence of birefringent needlelike crystals with rosette or wheat-sheaf-like arrangements in pulmonary cytology specimens is a reliable marker for the presence of Aspergillus infection, which may be detected before cultures are positive or a fungus ball is evident on X ray.     

Seroprevalence of Toxoplasma gondii Infection among HIV/AIDS Patients in Eastern China

Toxoplasmosis, a neglected tropical disease caused by the protozoan parasite Toxoplasma gondii, occurs throughout the world. Human T. gondii infection is asymptomatic in 80% of the population; however, the infection is life-threatening and causes substantial neurologic damage in immunocompromised patients such as HIV-infected persons. The major purpose of this study was to investigate the seroprevalence of T. gondii infection in subjects infected with HIV/AIDS in eastern China. Our findings showed 9.7% prevalence of anti-T. gondii IgG antibody in HIV/AIDS patients, which was higher than in intravenous drug users (2.2%) and healthy controls (4.7%), while no significant difference was observed in the seroprevalence of anti-Toxoplasma IgM antibody among all participants (P>0.05). Among all HIV/AIDS patients, 15 men (7.7%) and 10 women (15.9%) were positive for anti-T. gondii IgG antibody; however, no significant difference was detected in the seroprevalence of anti-Toxoplasma IgG antibody between males and females. The frequency of anti-Toxoplasma IgG antibody was 8.0%, 13.2%, 5.5%, and 0% in patients with normal immune function (CD4⁺ T-lymphocyte count ≥500 cells/ml), immunocompromised patients (cell count ≥200 and <500 cells/ml), severely immunocompromised patients (cell count ≥50 and <200 cells/ml), and advanced AIDS patients, respectively (cell count <50 cells/ml), while only 3 immunocompromised patients were positive for anti-T. gondii IgM antibody. The results indicate a high seroprevalence of T. gondii infection in HIV/AIDS patients in eastern China, and a preventive therapy for toxoplasmosis may be given to HIV/AIDS patients based on CD4⁺ T lymphocyte count.     

不同免疫状态肺隐球菌病临床特点分析

目的总结国内不同免疫状态人群肺隐球菌病（Pulmonary cryptococcosis,PC）临床特点,以提高该病的临床诊治水平。方法回顾性分析1998～2009年上海多家教学医院的100例Pc患者临床资料。结果既往无基础疾病史者占46．00％。临床以咳嗽、咳痰、发热为主要首发症状。无症状者多见于非免疫受损患者。非免疫受损PC病灶以胸膜下分布为主（55．22％）,单肺累及占72．97％,病灶位于肺野局部者占59．46％,病灶形态以结节／肿块影为主（55．41％）;而免疫受损患者病灶表现多样化,分布广泛而随机。19例患者行经支气管镜肺活检（TBLB）,病理结果阳性14例（73．68％）。36例患者行经皮肺穿刺活检（PCNB）,病理阳性26例（72．22％）。结论既往无基础疾病不能排除Pc可能。非免疫受损Pc患者病灶多靠近胸膜,病变较局限,形态以结节／肿块影多见。免疫受损患者病灶表现多样化,分布广泛而随机。TBLB和PCNB诊断PC阳性率较高,且两者可互为补充。     

Ten Challenges on Cryptococcus and Cryptococcosis

Cryptococcosis has become a significant public global health problem worldwide. Caused by two species, Cryptococcus neoformans or Cryptococcus gattii, this life-threatening infection afflicts not only immunocompromised individuals but also apparently immunocompetent subjects. Hence, cryptococcosis should no longer be considered merely an opportunistic infection. In this article, we focus on ten unanswered questions/topics in this field with the hope to stimulate discussion and research on these topics that would lead not only to a better understanding of the physiopathology of this disease but also to a better diagnosis and prognosis.     

Parasitoses and immunodepression

The immunodepression, related or not to AIDS, induces the emergence of opportunistic parasitosis and mycosis. Our objective is to analyze these pathogenic agents, their clinical expression and gravity in immunocompromised individuals. Our retrospective 9 years study reported parasitic and fungic infections complicating immunodepression. Among 31 HIV infected patients, we diagnosed the following parasitosis: Cryptosporidium (7 cases), Isospora belli (2 cases) and Enterocytozoon bieneusi (1 case). Pulmonary pneumocystosis was diagnosed in 6 cases, cerebral toxoplasmosis in 6 cases and meningo-cerebral cryptococcosis in 1 case. The systemic candidasis was diagnosed in 13 leukaemic patients. The intestinal anguilluliasis was found in 5 patients treated with cortico?ds for long periods. A case of Kala azar was observed in a 83 years man treated with cortico?ds. A disseminated aspergillosis occurred in a child with a Chediack Higashi syndrome. A gingivo-labial fusariosis was diagnosed in a leukaemic patient. This emergency of the new parasitic and fungal agents requires a better understanding of these affections in order to improve their early diagnosis and treatments.     

肺隐球菌病12例临床分析

目的 提高对隐球菌病的认识.方法 对确诊为肺隐球菌病的12例病例的临床资料进行回顾性分析.结果 12例病例中,男性8例,女性4例,年龄31～68岁,平均年龄(51.8±12.6)岁,6例伴有基础疾病,但无1例有鸟类接触史;有临床症状者10例,其中咳嗽8例,咯痰3例,胸痛4例,发热2例,有体征者仅2例;胸部影像表现为:1...     

First reportedNocardia otitidiscaviarum infection in an AIDS patient in Italy

Nocardiosis is a well-described infection in immunocompromised patients, and has been rarely documented in patients with AIDS.Nocardia asteroides is the most frequently isolated etiologic agent. Rare cases are due toN. brasiliensis andN. otitidiscaviarum. This work describes the first case of nocardiosis in Italy caused byN. otitidiscaviarum in an AIDS patient. A 31 year-old intravenous drug abuser with a diagnosis of full-blown AIDS, presented with high fever and lymphadenitis with a fistula draining copious purulent discharge. Broad-spectrum antibiotic therapy was initiated, but the patient did not show any improvement. Direct examination of the pus revealed numerous gram positive rods. When culturedN. otitidiscavarium was isolated and identified by morphological and biochemical tests.