Naegleria and Acanthamoeba infections: review

Infections caused by small, free-living amebas are still unfamiliar to many clinicians, pathologists, and laboratorians. As of 31 July 1989, more than 140 cases of primary amebic meningoencephalitis caused by Naegleria fowleri and more than 40 cases of granulomatous amebic encephalitis caused by Acanthamoeba species (including two cases in patients with AIDS) and possibly by other free-living amebas had occurred worldwide. The recent increase in acanthamoeba keratitis (more than 200 cases), especially in contact lens wearers, has generated new interest in this group of amebas. Effective treatment is still lacking. Risk factors, clinical manifestations, and laboratory parameters helpful in the recognition of infections of the central nervous system (i.e., granulomatous amebic encephalitis and primary amebic meningoencephalitis) and acanthamoeba keratitis are reviewed.     

Acanthamoeba meningoencephalitis presenting as neuropsychiatric lupus in a pediatric patient

We present the case of a 16-year-old patient with systemic lupus erythematosus who presented with altered mental status and regressive behaviour. She was worked up and empirically treated for common and opportunistic infectious agents. All work-up was negative and after an extensive course of antibiotics she was treated for neuropsychiatric lupus with cytoxan. She initially responded, but this was short-lived and she eventually became comatose and passed away. On brain biopsy she was found to have numerous trophozoites with round nucleus, prominent nucleolus and thin nuclear membrane. Methenamine silver stain showed encysted amoeba, corresponding with a diagnosis of acanthamoeba meningoencephalitis. Making the diagnosis of acanthamoeba meningoencephalitis requires a high degree of suspicion. Specific serum antibodies may not be a reliable measure in immunocompromised patients and trophozoites in CSF can be confused with monocytes. Brain biopsy may be required to make a definitive diagnosis. It is important for clinicians treating immunocompromised patients to keep this agent in mind in an immunocompromised patient with neurological manifestations. Acanthamoeba infections have only been reported in a small handful of patients and, to our knowledge, this is the first reported case in the United States.     

Balamuthia mandrillaris meningoencephalitis: the first case in southeast Asia

We present a case of 23-year-old man with acute meningoencephalitis, accompanied by inflammation of a nasal ulcer. He had been healthy until six months prior to admission to the hospital when he had a motorcycle accident. A star-shaped wound at his nose was incurred after falling into a swamp. A computed tomogram of the brain showed two nonenhancing hypodense lesions at the left caudate nucleus and the right parietal lobe, ependymitis and leptomeningeal enhancement. A skin biopsy showed chronic noncaseous granulomatous inflammation without demonstrated microorganisms. The patient did not respond to the empirical treatment with cloxacillin, ceftriaxone, and amphotericin B, and eventually died on the thirteenth day of hospitalization. At autopsy, hematoxylin and eosin-stained brain sections showed a chronic necrotizing inflammation with numerous amebic trophozoites and rare cysts. Definitive identification of Balamuthia mandrillaris was made by fluorescent immunohistochemical analysis. There were 10 Naegleria fowleri primary amebic meningoencephalitis, eight Acanthamoeba granulomatous amebic encephalitis, and three Acanthamoeba meningitis in Thailand. To our knowledge, this case is the first reported case of B. mandrillaris in Southeast Asia.     

Naegleria: another pathogenic ameba studies in germfree guinea pigs

Free-living amebas of the genus Naegleria, of world-wide distribution and long considered harmless, have been linked etiologically with 57 fatal cases of primary amebic meningoencephalitis during the last decade. Naegleria from cultures derived from one of these fatal cases in Richmond, Virginia, have been inoculated intranasally, intraorally, into the conjunctival sac near the inner canthus of the eyes, and into induced skin lesions in adult germfree guinea pigs. Of 33 animals inoculated intranasally with 18 to 31 amebas, 31 developed a fatal encephalitis. There was considerable destruction of tissues of the cerebellum and the cerebrum and including the olfactory lobes. The meninges were involved to varying degrees in most of the animals. None of the animals inoculated by the three other routes developed either symptoms or lesions.     

Review of the human immune mechanisms directed against Entamoeba histolytica

The human immune mechanisms effective against the destructive parasite Entamoeba histolytica have not been established. Humoral responses develop with invasive disease but have not positively correlated with protection against recurrent invasive infection. Though complement is amebicidal, invasive strains of amebas may be resistant. Polymorphonuclear neutrophils have not been active in vitro against virulent amebic strains and could contribute to the pathogenesis of disease. In vitro studies have shown human activated monocyte-derived macrophages and cytotoxic T lymphocytes to be competent cells in killing virulent amebas. Soluble amebic protein preparations have been shown to be mitogenic for normal, uninfected human lymphocytes, apparently because the N-acetyl-D-galactosamine-inhibitable amebic lectin is present. Despite a lower T4:T8 ratio and a heterogeneous lymphocyte proliferation in response to mitogens, patients with amebic hepatic abscess develop sensitization to amebic antigens and specific effector mechanisms. Although antibody, complement, and nonimmune mechanisms, as well as parasite factors, may be important in determining the occurrence of invasive amebiasis, human cell-mediated immune mechanisms may play a major role in combating invasive infection due to E. histolytica.     

Tissue culture isolation of Toxoplasma from blood of a patient with AIDS

A man with acquired immunodeficiency syndrome and multiple opportunistic infections developed central nervous system signs, and results of computed tomography suggested brain abscess. Histologic study and culture of material obtained from the brain biopsy specimen revealed Aspergillus. The clot from a peripheral venous blood sample obtained at the time of biopsy was processed and cultured on a monolayer of L cells. Five days later, Toxoplasma tachyzoites were identified in the cell culture. We bring this case to the attention of the medical community to point out that inoculation of tissue cell cultures as for viral isolation may aid in the diagnosis of Toxoplasma infection in these and other immunocompromised patients.     

Amebicidal plants extracts

The free-living amoebae from genus Acanthamoeba are the causative agents of granulomatous amebic encephalitis (GAE), a chronic progressive disease of the central nervous system; amebic keratitis (AK), a chronic eye infection; amebic pneumitis (AP), a chronic lung infection, and skin infection. Chemotherapy of Acanthamoeba infection is problematic. The majority of infections have been fatal. Only a few cases are reported to have been treated successfully with very highly toxic drugs. The therapy might be succeed, if the diagnosis and therapy is made at very early stage of infection. In our experiments we used the following plant extracts: Solidago virgaurea, Solidago graminifolia, Rubus chamaemorus, Pueraria lobata, and natural plants products as ellagic acid and puerarin. Those therapeutic agents and plants extracts have been tested in vitro for amebicidal or amebostatic activity against pathogenic Acanthamoeba spp. Our results showed that methanol extracts obtained from plants are active against axenic pathogenic Acanthamoeba sp. trophozoites in vitro at concentration below 0.1 mg/ml. Further studies are needed to investigate whether these extracts are also effective in vivo in animal model of infection with Acanthamoeba sp.     

Thoracic amebiasis

Pleuropulmonary amebiasis is the common and pericardial amebiasis the rare form of thoracic amebiasis. Low socioeconomic conditions, malnutrition, chronic alcoholism, and ASD with left to right shunt are contributing factors to the development of pulmonary amebiasis. Although no age is exempt, it commonly occurs in patients aged 20 to 40 years, with an adult male to female ratio of 10:1. Children rarely develop thoracic amebiasis: when it does occur there is an equal sex distribution. The infection usually spreads to the lungs by extension of an amebic liver abscess. Infection may pass to the thorax directly from the primary intestinal lesion through hematogenous spread, however. Lymphatic spread is one possible route. Inhalation of dust containing cysts and aspiration of cysts or trophozoites of E histolytica in the lungs are some other hypothetical routes. The lung is the second most common extraintestinal site of amebic involvement after the liver. Usually the lower lobe, and sometimes the middle lobe of the right lung, are affected, but it may affect any lobe of the lungs. The patient develops fever and right upper quadrant pain that is referred to the tip of the right shoulder or in between the scapula. Hemophtysis is common. The diagnosis of thoracic amebiasis is suggested by the combination of an elevated hemidiaphragm (usually right), hepatomegaly, pleural effusion, and involvement of the right lung base in the form of haziness and obliteration of costophrenic and costodiaphragmatic angles. Infection is usually extended to the thorax by perforation of a hepatic abscess through the diaphragm and across an obliterated pleural space, producing pulmonary consolidation, abscesses, or broncho-hepatic fistula. Empyema develops when a liver abscess ruptures into the pleural space. Rarely, a posterior amebic liver abscess can burst into the inferior vena cava and develop an embolism of the inferior vena cava and thromboembolic disease of the lungs with congestive cardiac failure or corpulmonale. Diagnosis by finding E histolytica in stool specimens is of limited value. In a limited number of cases amebae might be found in aspirated pus or expectorated sputum. "Anchovy sauce-like" pus or sputum may be found. Presence of bile in sputum indicates that the pus is of liver origin. Serological tests are of immense value in diagnosis. Liver enzymes are usually normal and neutrophilic leucocytosis may or may not be found. ESR is invariably elevated. Anti-amebic antibodies can be detected by ELISA, IFAT, and IHA. Amebic antigen can be detected from serum and pus by ELISA. Detection of Entamoeba DNA in pus or sputum may be a sensitive and specific method. Pleuropulmonary amebiasis is easily confused with other illnesses and is treated as pulmonary TB, bacterial lung abscesses, and carcinoma of the lung. A single drug regimen with metronidazole with supportive therapy usually cures patients without residual anomalies. Aspiration of pus from empyema thoracis may be needed for confirmation and therapeutic purposes. The pericardium is usually involved by direct extension from the amebic abscess of the left lobe of the liver, sometimes from the right lobe of the liver, and rarely from the lungs or pleura. An initial accumulation of serous fluid due to reactive pericarditis followed by intrapericardial rupture may develop either (1) acute onset of severe symptoms with chest pain, dyspnea, and cardiac tamponade, shock, and death, or (2) progressive effusion with thoracic cage pain, progressive dyspnea, and fever. Chest radiograph, ultrasound examination, and CT scan usually confirm the presence of a liver abscess in continuity with the pericardium and fluid within the pericardial sac with or without the fistulous tract. Echocardiography may demonstrate fluid in the pericardial cavity. Patients should be cared for in the ICU and ambecides should be started without delay. Pericardiocentesis usually confirms the diagnosis and improves the general condition of the patient. Aspiration of the accumulated fluid should be performed urgently in cardiac tamponade; repeated aspiration may be needed. Surgical drainage should be done if needed. Acanthamoeba, a free-living ameba, may also infect the lungs in the form of pulmonary nodular infiltration and pulmonary edema in association with amebic meningoencephalitis in immunocompromised patients. It usually spreads to the meninges of the brain by way of the blood from its primary lesion in the lung or skin. Early diagnosis and institution of treatment may be life saving for these patients. A literature review shows that HIV/AIDS patients are not prone to infection with E histolytica. It is now clear that there are an increasing number of HIV-seropositive patients among amebic liver abscess patients, however, which suggests that although the incidence of intestinal infection is not high among HIV-seropositive or AIDS patients they are more susceptible to an invasive form of the disease.     

Experimental pneumonitis and encephalitis caused by acanthamoeba in mice: pathogenesis and ultrastructural features.

For a more precise definition of the clinicopathological features of experimental acanthamoebic infection in mice, trophozoites of Acanthamoeba castellanii and Acanthamoeba polyphaga were instilled intranasally into adult white mice. Eight to 20 days after inoculation, severe pulmonary disease developed; one to two days later, neurological signs ensued. On pathologic examination an amebic broncho-pneumonia associated with encephalitis was found. Trophozoites and cysts were seen in lung and brain. Although Naegleria is spread by the olfactory route, cerebral lesions produced by Acanthamoeba might result principally from hematogenous carriage from the lungs. Other differences between infections caused by Naegleria and those caused by Acanthamoeba in mice also exist and serve to emphasize that when natural infections with Acanthamoeba occur, a distinct clinicopathological entity may be produced.     

Chagasic meningoencephalitis: case report of a recently included AIDS-defining illness in Brazil

Recently, reactivation of Chagas disease (meningoencephalitis and/or myocarditis) was included in the list of AIDS-defining illnesses in Brazil. We report a case of a 52-year-old patient with no history of previous disease who presented acute meningoencephalitis. Direct examination of blood and cerebrospinal fluid (CSF) showed Trypanosoma cruzi. CSF culture confirmed the diagnosis. Serological assays for T. cruzi and human immunodeficiency virus (HIV) were positive. Despite treatment with benznidazol and supportive measures, the patient died 24 hours after hospital admission. In endemic areas, reactivation of Chagas disease should always be considered in the differential diagnosis of meningoencephalitis among HIV-infected patients, and its presence is indicative of AIDS.     

Mycobacterium haemophilum in immunocompromised patients.

Mycobacterium haemophilum, a recently described pathogen, can cause an array of symptoms in immunocompromised patients. To date, 90 patients with this infection have been described worldwide. We report our institution's experience with 23 patients who were treated from 1990 through 2000. Fourteen patients had undergone bone marrow transplantation, 5 were infected with human immunodeficiency virus, 3 had hematologic malignancies, and 1 had no known underlying immunosuppression. Clinical syndromes on presentation included skin lesions alone in 13 patients, arthritis or osteomyelitis in 4 patients, and lung disease in 6 patients. Although patients with skin or joint involvement had favorable outcomes, 5 of 7 patients with lung infection died. Prolonged courses of multidrug therapy are required for treatment. A diagnosis of M. haemophilum infection must be considered for any immunocompromised patient for whom acid-fast bacilli are identified in a cutaneous, synovial fluid or respiratory sample or for whom granulomas are identified in any pathological specimen.     

Herpes simplex virus type 2 meningoencephalitis resistant to acyclovir in a patient with AIDS

A case is reported of relapsing fatal meningoencephalitis caused by a neurovirulent thymidine kinase-positive (TK+) type 2 herpes simplex virus (HSV) that developed thymidine kinase deficiency (TK-) during intravenous acyclovir therapy. A patient with AIDS was admitted for acyclovir treatment of a persistent perirectal herpetic ulcer. He subsequently developed meningoencephalitis. A TK+ type 2 HSV was isolated from a brain biopsy specimen. A progressive and fatal relapse occurred, and a TK- type 2 HSV was isolated from his cerebrospinal fluid. Restriction endonuclease analysis of viral DNA from perianal, brain, and cerebrospinal fluid isolates were similar, suggesting that they were the same viral strain. Animal virulence studies indicated significant cutaneous virulence in immunocompromised mice models for the TK- isolates. This case is notable because TK- HSV have, in the past, lacked neurovirulence and because acyclovir resistance developed during therapy and caused the patient's death.     

New spectrum of fungal infections in patients with cancer

We report on 44 cancer patients who had serious infections with unusual fungal pathogens and who were cared for at our cancer center between 1974 and 1986. Twelve different fungal species accounted for these infections, including Trichosporon beigelii, Fusarium species, Geotrichum candidum, Curvularia species, Drechslera species, Penicillium species (but not Penicillium marneffei), Rhodotorula rubra, Pseudallescheria boydii, Pichia farinosa, Torulopsis pintolopesii, Saccharomyces cerevisiae, and Cunninghamella bertholletiae. Skin lesions were noted in seven patients, and sinusitis occurred in four. Twenty-four patients had disseminated infection, 12 had involvement of a single organ, and eight had fungemia alone. Features that correlated with a poor prognosis were persistent neutropenia and disseminated visceral infection but not fungemia alone. We suggest that unusual fungi have now emerged as significant pathogens in this patient population. Fungal sinusitis, previously caused by Aspergillus species and the phycomycetes, also occurs as a result of some of these newly recognized fungi. A high level of suspicion should be maintained when any of these unusual fungi are cultured from clinical specimens from immunocompromised patients.     

Acanthamoeba keratitis in a non-contact lens wearer with human immunodeficiency virus

Acanthamoeba keratitis is potentially blinding and often associated with contact lens wearing. A human immunodeficiency virus (HIV)-positive patient, a non-contact lens wearer, presented with keratitis. She experienced a protracted course of disease, characterized by exacerbations and remissions, and was treated with various topical antibiotics and steroids. 13 months after symptom onset the eye was removed owing to serious scarring of cornea and unbearable pain. Microbiological and histopathological examination of the cornea showed Acanthamoeba. In non-contact lens wearers suffering from Acanthamoeba keratitis the diagnosis is delayed, pathognomonic features are often not seen and visual outcome is usually poor. There is no known relation between HIV infection and Acanthamoeba keratitis.     

Listeriosis in patients infected with human immunodeficiency virus

Although resistance to Listeria monocytogenes infection requires intact T cell-mediated immunity, only 20 patients with human immunodeficiency virus (HIV) infection and listeriosis (including one patient described herein) have been reported to date. Listeriosis developed before AIDS in five cases. Syndromes included meningitis in nine cases, bacteremia in nine, brain abscess in one, and endocarditis in one. Eighteen patients were treated with ampicillin, penicillin, or amoxicillin with or without aminoglycosides. Clinical and microbiologic responses were obtained in one patient with bacteremia treated with vancomycin and in one patient with meningitis treated with trimethoprim-sulfamethoxazole. Three of the nine patients with meningitis died, as did the patient with brain abscess. All nine patients with bacteremia and the patient with endocarditis survived. No case of relapse was documented. L. monocytogenes, although uncommon, should be considered in the differential diagnosis of febrile illness, meningitis, and brain abscess in patients with HIV infection.     

Brain biopsy in patients with acquired immunodeficiency syndrome: diagnostic value, clinical performance, and survival time

BACKGROUND: Despite extensive discussion in recent years, brain biopsy in patients positive for human immunodeficiency virus who manifest cerebral mass lesions remains an ill-defined step in management. METHODS: Prebiopsy data of 26 human immunodeficiency virus-positive patients with cerebral mass lesions who underwent computed tomography-guided stereotactic brain biopsy (SBB) were reviewed by a specialist in infectious diseases and by a neuroradiologist to establish a clinical diagnosis and a treatment plan for each patient. The postbiopsy diagnosis was compared with the prebiopsy diagnosis. Long-term patient outcome after SBB was recorded by means of a clinical performance scale to estimate its impact on life expectancy and clinical performance. RESULTS: The SBB was diagnostic in 25 patients (96%). Potentially treatable disease was diagnosed in 21 patients (81%), and specific therapy was initiated in 17 patients (65%); 10 patients (39%) were able to complete therapy. The SBB corroborated the clinical diagnosis in 13 (52%) of 25 patients. The group with identical clinical and biopsy-proved diagnoses showed significantly better response to therapy (P = .02), clinical performance (P = .04), and survival after biopsy (P = .01), as compared with the group with different clinical and biopsy-proved diagnosis, although no significant difference was found for the degree of immunosuppression. Only completion of the treatment plan increased life expectancy significantly (P = .008). CONCLUSIONS: These data show that in human immunodeficiency virus-positive patients with brain mass lesions, SBB has a high diagnostic yield. A subgroup of patients will benefit from specific therapy guided by the SBB result. The procedure should, however, be strictly limited to patients able to tolerate specific therapy.     

Human immunodeficiency virus recovery from bronchoalveolar lavage fluid in patients with AIDS

We cultured bronchoalveolar lavage fluid for the human immunodeficiency virus (HIV) from 23 consecutive patients with acquired immunodeficiency syndrome (AIDS) and pulmonary symptoms. We also included a nonconsecutive AIDS patient with recent worsening of respiratory symptoms who had had lymphocytic interstitial pneumonitis (LIP) diagnosed six months earlier. Infectious HIV was present in the cellular fraction from two of the 23 consecutive patients and in the patient with LIP. No virus was isolated from the cell-free portion of the centrifuged fluids. The patients from whom HIV was cultured were not distinguishable from other patients by clinical, radiographic, or laboratory data, and their subsequent course did not appear to differ. One patient with a positive HIV culture had organizing pneumonia without evidence of LIP at autopsy three weeks after lavage. This study demonstrates that HIV can be cultured from cells obtained by bronchoalveolar lavage and suggests that its presence is not associated with a single specific pulmonary histologic pattern.     

Fulminant amebic colitis in an HIV-infected homosexual man

We present a case of fulminant amebic colitis in a human immunodeficiency virus (HIV)-infected homosexual man. The patient developed colonic perforation over a short time despite empirical therapy with metronidazole, and underwent right hemicolectomy. Amebic colitis was pathologically diagnosed by identifying invasive trophozoites of Entamoeba in a surgical specimen. Amebic colitis is one of the important differential diagnoses of acute abdomen in HIV-infected patients and/or homosexual men, especially in East Asia. Although fulminant amebic colitis is a rare manifestation of amebiasis, early diagnosis and treatment are thought to be important to improve the outcome of this highly fatal complication.     

Brain lesions in patients with acquired immunodeficiency syndrome

Infections involving the brain have become a major complication in patients with acquired immunodeficiency syndrome. We have reviewed 48 cases of central nervous system lesions in patients with acquired immunodeficiency syndrome. and its related complex. All patients had computed tomographic scans with contrast performed; 31 of 48 were intravenous drug abusers. Computed tomographic abnormalities found included 21 patients with multiple ring-enhancing lesions, 13 with single ring-enhancing lesions, 11 with single hypodense lesions, and three with multiple hypodense lesions. Twenty-five patients had a positive serologic reaction for Toxoplasma. Sixteen patients had brain tissues examined. Of the 16 patients, six had cerebral Toxoplasma (one with concomitant Mycobacterium tuberculosis), and ten had diagnoses other than toxoplasmosis (three of whom had a positive serologic reaction for Toxoplasma). Two patients had M tuberculosis; one patient had Nocardia asteroides with Salmonella enteritidis. Of the remaining seven patients, three had encephalitis of unknown cause, two had inconclusive tissue diagnoses, one had progressive multifocal leukoencephalopathy, and one had vasculitis. In the population of intravenous drug users, brain lesions from diseases other than toxoplasmosis may be just as prevalent. Attempts to obtain a diagnosis from brain tissue is highly recommended to permit the design of effective and specific therapy for those diseases amenable to therapy.     

Ileocecal masses in patients with amebic liver abscess： Etiology and management

AIM:To assess the causes of ileocecal mass in patientswith amebic liver abscess.METHODS:Patients with amebic liver abscess andileocecal mass were carefully examined and investigatedby contrast-enhanced CT scan followed by colonoscopyand histological examination of biopsy materials fromlesions during colonoscopy.RESULTS:Ileocecal masses were found in seventeenpatients with amebic liver abscess.The cause of themass was ameboma in 14 patients,cecal tuberculosisin 2 patients and adenocarcinoma of the cecum in 1patient.Colonic ulcers were noted in five of the six(83%)patients with active diarrhea at presentation.Theileocecal mass in all these patients was ameboma.Ulcerswere seen in only one of the 11(9%)patients withoutdiarrhea.The difference was statistically significant fromthe group with diarrhea(P<0.005).CONCLUSION:Ileocecal mass is not an uncommonfinding in patients with amebic liver abscess.Although,the ileocecal mass is due to ameboma formation in mostcases,it should not be assumed that this is the case inall patients.Colonoscopy and histological examinationof the target biopsies are mandatory to avoid missing amore sinister lesion.