Histoplasmosis due to Histoplasma capsulatum capsulatum and HIV infection

PURPOSE: Histoplasmosis due to Histoplasma capsulatum is a granulomatous fungic infection which appears opportunistic and disseminated in immunocompromised patients, especially among HIV patients in whom it can lead to death. Histoplasmosis is endemic in numerous areas worldwide, but in Europe most of the cases reported are imported. We describe the clinical features and the available diagnosis methods issued from our experience in French Guyana. METHODS: Contamination occurs by inhalation of spores contained in dust. Most endemic areas are located on the American continent, including the French West Indies, where the incidence of histoplasmosis among HIV patients in French Guyana varies from 1.2 to 2.2% per year. In non-immunocompromised patients, histoplasmosis is asymptomatic most of the time. In HIV patients, the disseminated form is common and may occur many years after exposure to the fungus. RESULTS: Non-specific symptoms, similar to those of either tuberculosis or other opportunistic infections, may reveal disseminated histoplasmosis in patients with AIDS. Early treatment (amphotericin B or itraconazole) is effective; however, it should be followed by a lifelong antifungic treatment (itraconazole) to prevent relapse. CONCLUSION: The infection should be suspected in any febrile HIV-infected patient with CD4 blood cell count < 200/mm3, if he/she ever travelled in an endemic zone. Direct examination of smear relating to clinical symptoms help guide diagnosis, while culture will confirm it after at least 4 weeks. Efficient serologic techniques for HIV-infected patients are not available in Europe.     

Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management

Pulmonary manifestations are the hallmark of histoplasmosis. Clinical syndromes range from asymptomatic infection to diffuse alveolar disease causing respiratory difficulty and even death. Serologic tests for antibodies and antigen detection are especially helpful in the diagnosis of histoplasmosis but are frequently overlooked. Detection of Histoplasma capsulatum antigen in bronchoalveolar lavage fluid may be particularly helpful in patients with acute pulmonary histoplasmosis or disseminated disease with pulmonary involvement. Topics of special importance for pulmonary disease specialists include the approach to the exclusion of histoplasmosis in the evaluation of patients with suspected sarcoidosis, differentiation of pulmonary histoplasmosis and malignancy in those with lung masses or mediastinal lymphadenopathy, and recognition and management of chronic pulmonary and mediastinal manifestations of histoplasmosis. Although histoplasmosis is mild and self-limited in most healthy individuals, antifungal therapy is indicated in those with acute diffuse pulmonary infection, chronic pulmonary histoplasmosis, progressive disseminated disease, and perhaps mediastinal adenitis accompanied by obstructive symptoms. Antifungal therapy to prevent reactivation of histoplasmosis during immunosuppressive therapy, or transition of mediastinal adenitis to fibrosing mediastinitis, although controversial, is not recommended. Several new drugs active against H. capsulatum offer alternatives in patients failing or intolerant of current therapies.     

Rupioid histoplasmosis: first case reported in an AIDS patient in Argentina

Disseminated histoplasmosis is a relatively common AIDS-defining illness, occurring in almost 4% of patients living in endemic areas and it may be the first clinical expression of the HIV infection. A broad spectrum of clinical skin lesions associated with Histoplasma capsulatum infection have been described in AIDS patients, such as erythematous macules, papules, nodules, and pustules. Herpetic, acneiform, erythema multiforme-like, molluscum contagiosum-like, vasculitic, and exfoliative forms have also been reported. To our knowledge, this is the first case of disseminated histoplasmosis in an AIDS patient presented as a rupioid eruption.     

Gastrointestinal histoplasmosis in patients with AIDS: case report and review.

Histoplasmosis is the most common endemic mycosis in individuals with AIDS, occurring in 2%-5% of this population. Infection is more likely to be disseminated than in immunocompetent individuals and generally presents insidiously with nonspecific symptoms. The gastrointestinal tract is involved in 70%-90% of cases of disseminated histoplasmosis, yet gastrointestinal histoplasmosis per se is infrequently encountered in patients with AIDS. The diagnosis of gastrointestinal histoplasmosis is often not suspected, particularly in areas of nonendemicity, and a delay in diagnosis may lead to increased morbidity and risk of death. Since antifungal therapy improves outcome for >80% of AIDS patients with histoplasmosis, it is essential that caregivers be aware of the varied presentations of gastrointestinal histoplasmosis in order to diagnose and to treat this potentially life-threatening infection effectively.     

Progressive disseminated histoplasmosis in the HIV population in Europe in the HAART era. Case report and literature review

Introduction

In highly endemic areas, up to 20 % of human immunodeficiency virus (HIV)-infected persons will develop progressive disseminated histoplasmosis (PDH). Europe is not endemic to histoplasmosis, and the disease is mainly found in immigrants often co-infected with HIV.

Methods

We present a case of a patient with HIV and PDH highlighting the possible diagnostic difficulties that may arise in a non-endemic area and review the literature of histoplasmosis in the context of HIV infection with special focus on Europe.

Discussion

When cellular immunity wanes (usually at CD4 T-lymphocyte counts <150 cells/μL) histoplasma infection, acquired earlier, can reactivate and disseminate. PDH is an acquired immune deficiency syndrome(AIDS)-defining disease and a life-threatening infection, with a clinical spectrum ranging from an acute, fatal course with lung infiltrates and respiratory failure, shock, coagulopathy and multi-organ failure, to a more subacute disease with focal organ involvement, pancytopenia and hepatosplenomegaly. Mortality rates remain high for untreated patients, but early diagnosis, proper antifungal treatment and early initiation of antiretroviral therapy have improved the prognosis.

Conclusion

European infectious diseases physicians, microbiologists and pathologists must be aware of histoplasmosis, particularly when facing HIV-infected immigrants from endemic areas. This is increasingly important due to migration and travel activities from these areas.     

American histoplasmosis in developing countries with a special focus on patients with HIV: diagnosis, treatment, and prognosis

PURPOSE OF REVIEW: Histoplasmosis due to Histoplasma capsulatum var capsulatum is a frequent systemic fungal infection in the Americas. Diagnostic and therapeutic options differ between North and South America. Disseminated histoplasmosis is an AIDS-defining infection. Prognostic factors of potentially severe presentations must be evaluated in order to facilitate the initial therapeutic choice. RECENT FINDINGS: Patients with HIV with disseminated infections presenting with severe pulmonary and renal impairment have a poor prognosis. Cutaneous presentations are more frequent in HIV patients in South America than in North America. A murine model has shown that South American isolates have a greater virulence that North American isolates. These differences are due in part to diagnostic delays in resource-poor countries. SUMMARY: Direct examination of May-Grünwald-Giemsa-stained smears or tissues in suspected histoplasmosis is a simple means of confirming the diagnosis in resource-poor settings. Studies of prognostic factors should further refine indication criteria to guide first-line treatment choice between amphotericin B and itraconazole. The association of tuberculosis and histoplasmosis is frequent in HIV patients and presents diagnostic and therapeutic challenges that may be difficult to resolve in resource-poor settings. It is important that affordable generic drugs for treating histoplasmosis be made widely available in resource-poor countries.     

HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health

OBJECTIVE: To describe initial viral dissemination to peripheral tissues and infectious body fluids during human primary HIV infection. DESIGN: Observational cohort study. METHODS: Blood plasma, cerebrospinal fluid (CSF), seminal plasma, cervicovaginal lavage fluid and/or saliva were sampled from 17 individuals with primary HIV infection (range of time from symptoms onset to sampling, 8--70 days) and one individual with early infection (168 days). Subjects' HIV-1 RNA levels in each fluid were compared with levels from antiretroviral-naive controls with established HIV infection. For study subjects, correlations were assessed between HIV-1 RNA levels and time from symptoms onset. Responses to antiretroviral therapy with didanosine + stavudine + nevirapine +/- hydroxyurea were assessed in each compartment. RESULTS: HIV-1 RNA levels were highest closest to symptoms onset in blood plasma (18 patients) and saliva (11 patients). CSF HIV-1 RNA levels (five patients) appeared lower closer to symptoms onset, although they were higher overall in primary versus established infection. Shedding into seminal plasma (eight patients) and cervicovaginal fluid (two patients) was established at levels observed in chronic infection within 3--5 weeks of symptoms onset. High-level seminal plasma shedding was associated with coinfection with other sexually transmitted pathogens. Virus replication was suppressed in all compartments by antiretroviral therapy. CONCLUSIONS: Peak level HIV replication is established in blood, oropharyngeal tissues and genital tract, but potentially not in CSF, by the time patients are commonly diagnosed with primary HIV infection. Antiretroviral therapy is unlikely to limit initial virus spread to most tissue compartments, but may control genital tract shedding and central nervous system expansion in primary infection.     

Gastrointestinal histoplasmosis ileal stricture successfully treated with through-the-scope balloon dilation in a patient with hyperimmunoglobulin M syndrome

Gastrointestinal histoplasmosis is common in patients with disseminated disease affecting both immunocompetent and immunocompromised patients. However, it is often unrecognized due to a lack of specific signs and symptoms. It has only rarely been reported to cause small bowel obstruction, during which surgical treatment was nearly always necessary. Little is known about the usefulness of endoscopic therapy in gastrointestinal histoplasmosis associated strictures. We report the case of a 32-year-old man with a history of hyperimmunoglobulin M syndrome who presented with small bowel obstruction secondary to disseminated gastrointestinal histoplasmosis. Treatment was successful with a through-the-scope balloon dilator in combination with medical therapy. This report adds to the limited data available on the benefit of endoscopic therapy in infectious strictures, particularly gastrointestinal histoplasmosis.     

A case of acquired immunodeficiency syndrome (AIDS) with histoplasmosis

Fungal infection is a major opportunistic infection in AIDS. Histoplasmosis is often seen in American AIDS, but only one case has been reported in Japan. We report a AIDS case of with histoplasmosis in Japan. The patient was a forty year old male living in the U.S from 1987 to 1990. He was diagnosed as candidial esophagitis in July, 1994, and human immunodeficiency virus type 1 (HIV) antibody positive led to a diagnosis of AIDS. He was admitted to our hospital with fever and lymphadenopathy (neck, abdomen) in August. The therapy for candidial esophagitis was successful and he was recovering, but he was newly diagnosed as atypical mycobacteriosis and Kaposi's sarcoma. Though the fever was slight, it persisted. He was discharged from our hospital in October. He was readmitted for a high fever and dehydration in December, but died after a week from disseminated intravascular coagulation (DIC). Histoplasma capsulatum was found by blood and ascites cultures on second admission. Many yeast like histoplasma cells in granuloma of the liver were found at autopsy. For moderate or severe histoplasmosis, amphotericin B is generally used as the first induction therapy. Fluconazole (FLCZ) is used as a maintenance therapy. We did not use amphotericin B, but used FLCZ because we did not diagnose histoplasmosis before death, and his general condition became worse. The effect of FLCZ therapy was unclear in our case because he had other infections. We expect that AIDS with histoplasimosis will increase in Japan through HIV infected patients infected in the U.S.A.     

Fever and high lactate dehydrogenase in HIV-positive patients from the Antilles and Surinam: histoplasmosis?

We describe four cases of HIV-positive patients, two from Surinam, one from the Dutch Antilles and one from Nigeria, who presented with a febrile illness and a high lactate dehydrogenase plasma level. In all four, the diagnosis of disseminated histoplasmosis was made, in three of them by liver biopsy. Two patients had retinal abnormalities compatible with a systemic fungal infection. Three patients were treated successfully with antifungal agents. One patient died. Between 2000 and 2006, only 14 patients with HIV have been found to have histoplasmosis in the Netherlands. Although histoplasmosis is not endemic in the Netherlands, physicians are more likely to see cases because of a growing number of HIV -positive immigrants from endemic regions.     

Deep fungal infection in systemic lupus erythematosus - three cases reported, literature reviewed.

Three patients with systemic lupus erythematosus (SLE) and deep fungal infection are described. Two patients had disseminated cryptococcal infection and the third disseminated histoplasmosis. Allwere receiving corticosteroids at the time fungal infection developed. One patient with disseminated cryptococcosis improved after treatment with amphotericin B and 5-fluorocytosine. The other patient with disseminated cryptococcosis died before adequate therapy could be given. The patient with histoplasmosis responded satisfactorily to amphotericin B. A survey of the literature revealed 30 additional cases of deep fungal infection in patients with SLE, most of whom were on corticosteroid therapy. The majority of the patients had candidiasis (14 patients); 11 patients had severe cryptococcal infection. Other fungal infections reported were histoplasmosis, aspergillois, coccidioidomycosis, and maduromycosis caused by Allerscheria boydii. Twenty-seven patients died; in 22 death was related to the fungal infection. The fungal infection was not diagnosed until necropsy in at least 11 persons. Deep fungal infections should be considered whenever patients with SLE have fever of unknown origin, diffuse pulmonary infiltrates, or unexplained CNS symptoms.     

The spectrum of respiratory mycoses in a referral hospital in north-western India

There has been an increasing recognition of respiratory mycoses in this country in the recent past. Candidiasis, aspergillosis and cryptococcosis have been reported from different centres. Occasional cases of histoplasmosis and sporotrichosis have also been reported. Infections with Pneumocystis carinii, which is now classified as a fungus, are being frequently diagnosed, especially in the immuno-compromised patients such as those on prolonged immunosuppressive therapy or with HIV infection. Although the clinical picture of respiratory mycoses resembles that of any other infection, the presentation in several cases is atypical and the diagnosis is delayed. In a review of our patients of respiratory fungal infections seen in the last few years, we found several interesting examples. We report here the general clinical spectrum of respiratory mycoses and some interesting cases seen at our Centre.     

Hepatobiliary Manifestations of the Acquired Immune Deficiency Syndrome

Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction. Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS. Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection. In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise. Cytomegaloviral infection may produce a hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis. About 10-20% of patients with AIDS have chronic hepatitis B infection. These patients tend to develop minimal hepatic inflammation and necrosis. The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms. Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure. Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms. As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver. Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction. Patients with a focal hepatic lesion should be considered for a guided liver biopsy. Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy. When performed for these indications, liver biopsy will demonstrate a significant disease involving the liver in about 50% of patients with AIDS and in about 25% of patients who are HIV seropositive but who are not known to have AIDS. The clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections.     

Progressive disseminated histoplasmosis in the acquired immunodeficiency syndrome: a model for disseminated disease

Progressive disseminated histoplasmosis (PDH) is a relatively common infectious illness in human immunodeficiency virus (HIV)-infected patients. In Houston, Texas, (which is moderately endemic for histoplasmosis) the frequency of PDH is 5% among patients with acquired immunodeficiency syndrome (AIDS), almost as high as that of those with cryptoccal disease. In highly endemic areas, the frequency of PDH in AIDS is even greater, up to 75% in some areas. It is likely that as the HIV epidemic continues to penetrate to more remote, highly endemic areas, more and more cases of PDH will occur. It is also clear that PDH may develop in HIV-infected patients who presently live in nonendemic areas, but who previously resided in endemic areas. It is important that all physicians who care for HIV-infected patients become thoroughly familiar with the clinical manifestation of this illness. Timely diagnosis depends on a high degree of diagnostic suspicion since the illness seldom presents with primary respiratory symptoms. It is prudent to consider PDH in the differential diagnosis of any systemic, wasting, febrile illness in HIV-infected individuals, especially if currently or in the past they have resided in areas endemic for the fungus. Similarly, whenever PDH is diagnosed in any patient who is in a high-risk group for HIV infection, prompt testing for HIV should be performed.     

Mycobacterium avium complex and other nontuberculous mycobacteria in patients with HIV infection

Nontuberculous mycobacteria (NTM) have been frequently identified as opportunistic pathogens in individuals with advanced human immunodeficiency virus (HIV) infection. The majority of these infections have been caused by members of the Mycobacterium avium-intracellulare complex (MAC). Disseminated MAC infection has generally been diagnosed late in the course of HIV infection, and it is often associated with persistent nonspecific symptoms of fever, generalized weakness, and weight loss. Abdominal pain and/or diarrhea with malabsorption may also occur in some patients. Despite frequent isolation of MAC organisms from respiratory secretions in these patients, significant pulmonary involvement has not been seen commonly with disseminated MAC infection. While MAC can be isolated from a variety of clinical specimens in infected individuals, culturing of blood is the single most useful diagnostic procedure to evaluate for MAC infection. The prognosis for disseminated MAC infection in HIV-infected patients has been poor, with a reported median survival of 7.4 months after diagnosis. The overall contribution of MAC infection to mortality in these patients has not been clearly delineated. Treatment of MAC infection in HIV-infected individuals using a variety of drug regimens has not been effective in clearing mycobacteremia or improving overall survival in the majority of patients. However, initiation of drug therapy for MAC may decrease the severity of disease symptoms in some patients. Several NTM other than MAC have also been reported as causing infection in HIV-infected patients. Many of these organisms are ubiquitous in the environment and are frequent colonizers of biologic specimens. Although many NTM are regarded as relatively avirulent, these organisms need to be recognized as potentially important pathogens in HIV-infected patients with significant immunosuppression.     

The treatment of oropharyngeal candidiasis in HIV-infected patients with oral amphotericin B suspension

Oropharyngeal candidiasis (OPC) is the most frequent opportunistic infection associated with HIV infection. Therapies such as topical clotrimazole and nystatin, as well as oral azoles, which had previously been effective prior to the advent of HIV, are increasingly only partially effective in OPC in HIV infection. The effectiveness of oral amphotericin B suspension for OPC is described in 17 HIV-infected patients whose response to other therapies had been unsatisfactory. Three patients yielded isolates of Candida albicans with a minimum inhibitory concentration (MIC) to fluconazole of >/=16 microg/mL. Eleven patients received amphotericin B suspension monotherapy. Of the 17 patients, the symptoms of six resolved entirely, seven patients partially responded, and four failed therapy. These data suggest that amphotericin B suspension may be a useful additional therapy for OPC in HIV-infected patients.     

Retroviral rebound syndrome after cessation of suppressive antiretroviral therapy in three patients with chronic HIV infection

BACKGROUND: Although viral rebound follows cessation of suppressive antiretroviral therapy in chronic HIV infection, a viremic clinical syndrome has not been described. OBJECTIVE: To describe a retroviral syndrome associated with cessation of effective antiretroviral therapy in chronic HIV infection. DESIGN: Case reports. SETTING: Outpatient HIV specialty clinics in Seattle, Washington, and Boston, Massachusetts. PATIENTS: Three patients with chronic HIV infection who discontinued suppressive antiretroviral therapy. MEASUREMENTS: Clinical course, plasma HIV RNA levels, and CD4 cell counts before, during, and after cessation of antiretroviral therapy. RESULTS: Within 6 weeks after stopping antiretroviral therapy, each patient experienced a clinical illness that resembled a primary HIV syndrome. This coincided with a marked increase in HIV RNA level and, in two of three patients, a decrease in CD4 cell count. After antiretroviral therapy was restarted, each patient's symptoms rapidly resolved in association with resuppression of HIV RNA and increase in CD4 cell count or percentage. CONCLUSION: A retroviral rebound syndrome similar to that seen in primary HIV syndrome can occur in patients with chronic HIV infection after cessation of suppressive antiretroviral therapy.     

Histoplasmosis in Patients With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS): Multicenter Study of Outcomes and Factors Associated With Relapse

Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis.Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91–55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL.Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.     

Disseminated Histoplasmosis in Early Human Immunodeficiency Virus Infection

Early human immunodeficiency virus (HIV) infection leads to transient immunosuppression followed by a quasi-homeostatic state with slow progression towards AIDS. Histoplasmosis has never been reported in early HIV. We present a case of disseminated histoplasmosis with documented recent seroconversion and review the literature regarding other opportunistic infections in early HIV.