Last data update: Oct 28, 2024. (Total: 48004 publications since 2009)
Records 1-30 (of 36 Records) |
Query Trace: Visvesvara GS[original query] |
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Three cases of neurologic syndrome caused by donor-derived microsporidiosis
Smith RM , Muehlenbachs A , Schaenmann J , Baxi S , Koo S , Blau D , Chin-Hong P , Thorner AR , Kuehnert MJ , Wheeler K , Liakos A , Jackson JW , Benedict T , da Silva AJ , Ritter JM , Rollin D , Metcalfe M , Goldsmith CS , Visvesvara GS , Basavaraju SV , Zaki S . Emerg Infect Dis 2017 23 (3) 387-395 In April 2014, a kidney transplant recipient in the United States experienced headache, diplopia, and confusion, followed by neurologic decline and death. An investigation to evaluate the possibility of donor-derived infection determined that 3 patients had received 4 organs (kidney, liver, heart/kidney) from the same donor. The liver recipient experienced tremor and gait instability; the heart/kidney and contralateral kidney recipients were hospitalized with encephalitis. None experienced gastrointestinal symptoms. Encephalitozoon cuniculi was detected by tissue PCR in the central nervous system of the deceased kidney recipient and in renal allograft tissue from both kidney recipients. Urine PCR was positive for E. cuniculi in the 2 surviving recipients. Donor serum was positive for E. cuniculi antibodies. E. cuniculi was transmitted to 3 recipients from 1 donor. This rare presentation of disseminated disease resulted in diagnostic delays. Clinicians should consider donor-derived microsporidial infection in organ recipients with unexplained encephalitis, even when gastrointestinal manifestations are absent. |
Diagnosis, clinical course, and treatment of primary amoebic meningoencephalitis in the United States, 1937-2013
Capewell LG , Harris AM , Yoder JS , Cope JR , Eddy BA , Roy SL , Visvesvara GS , Fox LM , Beach MJ . J Pediatric Infect Dis Soc 2015 4 (4) e68-75 BACKGROUND: Primary amoebic meningoencephalitis (PAM) is a rapidly progressing waterborne illness that predominately affects children and is nearly always fatal. PAM is caused by Naegleria fowleri, a free-living amoeba found in bodies of warm freshwater worldwide. METHODS: We reviewed exposure location, clinical signs and symptoms, diagnostic modalities, and treatment from confirmed cases of PAM diagnosed in the United States during 1937-2013. Patients were categorized into the early (ie, flu-like symptoms) or late (ie, central nervous system signs) group on the basis of presenting clinical characteristics. Here, we describe characteristics of the survivors and decedents. RESULT: The median age of the patients was 12 years (83% aged ≤18 years); males (76%) were predominately affected (N = 142). Most infections occurred in southern-tier states; however, 4 recent infections were acquired in northern states: Minnesota (2), Kansas (1), and Indiana (1). Most (72%) of the patients presented with central nervous system involvement. Cerebrospinal fluid analysis resembled bacterial meningitis with high opening pressures, elevated white blood cell counts with predominantly neutrophils (median, 2400 cells/muL [range, 5-26 000 cells/muL]), low glucose levels (median, 23 mg/dL [range, 1-92 mg/dL]), and elevated protein levels (median, 365 mg/dL [range, 24-1210 mg/dL]). Amoebas found in the cerebrospinal fluid were diagnostic, but PAM was diagnosed for only 27% of the patients before death. Imaging results were abnormal in approximately three-fourths of the patients but were not diagnostic for amoebic infection. Three patients in the United States survived. CONCLUSIONS: To our knowledge, this is the first comprehensive clinical case series of PAM presented in the United States. PAM is a fatal illness with limited treatment success and is expanding into more northern regions. Clinicians who suspect that they have a patient with PAM should contact the US Centers for Disease Control and Prevention at 770-488-7100 (available 24 hours/day, 7 days/week) to discuss diagnostic testing and treatment options (see cdc.gov/naegleria). |
Malignant Transformation of Hymenolepis nana in a Human Host.
Muehlenbachs A , Bhatnagar J , Agudelo CA , Hidron A , Eberhard ML , Mathison BA , Frace MA , Ito A , Metcalfe MG , Rollin DC , Visvesvara GS , Pham CD , Jones TL , Greer PW , Velez Hoyos A , Olson PD , Diazgranados LR , Zaki SR . N Engl J Med 2015 373 (19) 1845-52 Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficiency virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer. |
Assessment of blood-brain barrier penetration of miltefosine used to treat a fatal case of granulomatous amebic encephalitis possibly caused by an unusual Balamuthia mandrillaris strain
Roy SL , Atkins JT , Gennuso R , Kofos D , Sriram RR , Dorlo TP , Hayes T , Qvarnstrom Y , Kucerova Z , Guglielmo BJ , Visvesvara GS . Parasitol Res 2015 114 (12) 4431-9 Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 mug/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 mug/mL. These are the first results confirming some blood-brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug's toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities. |
In vitro growth, cytopathic effects and clearance of monolayers by clinical isolates of Balamuthia mandrillaris in human skin cell cultures
Yera H , Dupouy-Camet J , Jackson JW , Sriram R , Sweat S , Goldstein JM , Visvesvara GS . Exp Parasitol 2015 156 61-7 Balamuthia mandrillaris is a free-living ameba (FLA) that has been isolated or its DNA identified in soil, dust and water. It causes a fatal central nervous system infection in humans and animals. Although it is environmental as Acanthamoeba and Naegleria fowleri, the two other free-living amebae that also cause CNS infections in humans and other animals, Balamuthia does not feed on bacteria as the other FLA. In the laboratory, it can be grown on a variety of mammalian cell cultures. In this study we examined the ability of three different Balamuthia isolates to grow on several different human skin cell cultures including the WT/A keratinocyte cell cultures. A corneal isolate of Acanthamoeba castellanii was used for comparison. |
Identification of Giardia duodenalis and Enterocytozoon bieneusi in an epizoological investigation of a laboratory colony of prairie dogs, Cynomys ludovicianus.
Roellig DM , Salzer JS , Carroll DS , Ritter JM , Drew C , Gallardo-Romero N , Keckler MS , Langham G , Hutson CL , Karem KL , Gillespie TR , Visvesvara GS , Metcalfe MG , Damon IK , Xiao L . Vet Parasitol 2015 210 91-7 Since 2005, black-tailed prairie dogs (Cynomys ludovicianus) have been collected for use as research animals from field sites in Kansas, Colorado, and Texas. In January of 2012, Giardia trophozoites were identified by histology, thin-section electron microscopy, and immunofluorescent staining in the lumen of the small intestine and colon of a prairie dog euthanized because of extreme weight loss. With giardiasis suspected as the cause of weight loss, a survey of Giardia duodenalis in the laboratory colony of prairie dogs was initiated. Direct immunofluorescent testing of feces revealed active shedding of Giardia cysts in 40% (n=60) of animals held in the vivarium. All tested fecal samples (n=29) from animals in another holding facility where the index case originated were PCR positive for G. duodenalis with assemblages A and B identified from sequencing triosephosphate isomerase (tpi), glutamate dehydrogenase (gdh), and beta-giardin (bg) genes. Both assemblages are considered zoonotic, thus the parasites in prairie dogs are potential human pathogens and indicate prairie dogs as a possible wildlife reservoir or the victims of pathogen spill-over. Molecular testing for other protozoan gastrointestinal parasites revealed no Cryptosporidium infections but identified a host-adapted Enterocytozoon bieneusi genotype group. |
Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis
Linam WM , Ahmed M , Cope JR , Chu C , Visvesvara GS , da Silva AJ , Qvarnstrom Y , Green J . Pediatrics 2015 135 (3) e744-8 Naegleria fowleri is a thermophilic, free-living ameba that causes primary amebic meningoencephalitis. The infections are nearly always fatal. We present the third well-documented survivor of this infection in North America. The patient's survival most likely resulted from a variety of factors: early identification and treatment, use of a combination of antimicrobial agents (including miltefosine), and management of elevated intracranial pressure based on the principles of traumatic brain injury. |
Transmission of Balamuthia mandrillaris through solid organ transplantation: utility of organ recipient serology to guide clinical management
Gupte AA , Hocevar SN , Lea AS , Kulkarni RD , Schain DC , Casey MJ , Zendejas-Ruiz IR , Chung WK , Mbaeyi C , Roy SL , Visvesvara GS , da Silva AJ , Tallaj J , Eckhoff D , Baddley JW . Am J Transplant 2014 14 (6) 1417-24 A liver, heart, iliac vessel and two kidneys were recovered from a 39-year-old man who died of traumatic head injury and were transplanted into five recipients. The liver recipient 18 days posttransplantation presented with headache, ataxia and fever, followed by rapid neurologic decline and death. Diagnosis of granulomatous amebic encephalitis was made on autopsy. Balamuthia mandrillaris infection was confirmed with immunohistochemical and polymerase chain reaction (PCR) assays. Donor and recipients' sera were tested for B. mandrillaris antibodies. Donor brain was negative for Balamuthia by immunohistochemistry and PCR; donor serum Balamuthia antibody titer was positive (1:64). Antibody titers in all recipients were positive (range, 1:64-1:512). Recipients received a four- to five-drug combination of miltefosine or pentamidine, azithromycin, albendazole, sulfadiazine and fluconazole. Nausea, vomiting, elevated liver transaminases and renal insufficiency were common. All other recipients survived and have remained asymptomatic 24 months posttransplant. This is the third donor-derived Balamuthia infection cluster described in solid organ transplant recipients in the United States. As Balamuthia serologic testing is only available through a national reference laboratory, it is not feasible for donor screening, but may be useful to determine exposure status in recipients and to help guide chemotherapy. |
Balamuthia mandrillaris encephalitis: survival of a child with severe meningoencephalitis and review of the literature
Moriarty P , Burke C , McCrossin D , Campbell R , Cherian S , Shahab MS , Visvesvara GS , Nourse C . J Pediatric Infect Dis Soc 2014 3 (1) e4-e9 Balamuthia mandrillaris causes granulomatous amoebic encephalitis, which is frequently fatal. There are few reports of survival in children. A 4-year-old child developed severe meningoencephalitis with multiple intracranial ring-enhancing lesions. Empiric therapy was commenced after a biopsy was performed, and the patient had a good clinical response. Molecular testing and indirect immunofluorescence later confirmed the diagnosis of Balamuthia encephalitis. Diagnosis of Balamuthia encephalitis is often delayed. The literature is reviewed with particular reference to reported survival. Prompt tissue diagnosis and initiation of therapy are common features among survivors. In previous reports, miltefosine was not used to treat children, but it was well tolerated in this case and should be considered as a therapeutic option. |
Microsporidiosis acquired through solid organ transplantation a public health investigation
Hocevar SN , Paddock CD , Spak CW , Rosenblatt R , Diaz-Luna H , Castillo I , Luna S , Friedman GC , Antony S , Stoddard RA , Tiller RV , Peterson T , Blau DM , Sriram RR , Da Silva A , De Almeida M , Benedict T , Goldsmith CS , Zaki SR , Visvesvara GS , Kuehnert MJ . Ann Intern Med 2014 160 (4) 213-220 BACKGROUND: Encephalitozoon cuniculi, a microsporidial species most commonly recognized as a cause of renal, respiratory, and central nervous system infections in immunosuppressed patients, was identified as the cause of a temporally associated cluster of febrile illness among 3 solid organ transplant recipients from a common donor. OBJECTIVE: To confirm the source of the illness, assess donor and recipient risk factors, and provide therapy recommendations for ill recipients. DESIGN: Public health investigation. SETTING: Two transplant hospitals and community interview with the deceased donor's family. PATIENTS: Three transplant recipients and the organ donor. MEASUREMENTS: Specimens were tested for microsporidia by using culture, immunofluorescent antibody, polymerase chain reaction, immunohistochemistry, and electron microscopy. Donor medical records were reviewed and a questionnaire was developed to assess for microsporidial infection. RESULTS: Kidneys and lungs were procured from the deceased donor and transplanted to 3 recipients who became ill with fever 7 to 10 weeks after the transplant. Results of urine culture, serologic, and polymerase chain reaction testing were positive for E. cuniculi of genotype III in each recipient; the organism was also identified in biopsy or autopsy specimens in all recipients. The donor had positive serologic test results for E. cuniculi. Surviving recipients received albendazole. Donor assessment did not identify factors for suspected E. cuniculi infection. LIMITATION: Inability to detect organism by culture or polymerase chain reaction in donor due to lack of autopsy specimens. CONCLUSION: Microsporidiosis is now recognized as an emerging transplant-associated disease and should be considered in febrile transplant recipients when tests for routinely encountered agents are unrevealing. Donor-derived disease is critical to assess when multiple recipients from a common donor are ill. |
Serologic survey for exposure following fatal Balamuthia mandrillaris infection
Jackson BR , Kucerova Z , Roy SL , Aguirre G , Weiss J , Sriram R , Yoder J , Foelber R , Baty S , Derado G , Stramer SL , Winkelman V , Visvesvara GS . Parasitol Res 2014 113 (4) 1305-11 Granulomatous amebic encephalitis (GAE) from Balamuthia mandrillaris, a free-living ameba, has a case fatality rate exceeding 90 % among recognized cases in the USA. In August 2010, a GAE cluster occurred following transplantation of infected organs from a previously healthy landscaper in Tucson, AZ, USA, who died from a suspected stroke. As B. mandrillaris is thought to be transmitted through soil, a serologic survey of landscapers and a comparison group of blood donors in southern Arizona was performed. Three (3.6 %) of 83 serum samples from landscapers and 11 (2.5 %) of 441 serum samples from blood donors were seropositive (p = 0.47). On multivariable analysis, county of residence was associated with seropositivity, whereas age, sex, and ethnicity were not. Exposure to B. mandrillaris, previously unexamined in North America, appears to be far more common than GAE in Southern Arizona. Risk factors for disease progression and the ameba's geographic range should be examined. |
Diagnostic challenges in Balamuthia mandrillaris infections
Lobo SA , Patil K , Jain S , Marks S , Visvesvara GS , Tenner M , Braun A , Wang G , El Khoury MY . Parasitol Res 2013 112 (12) 4015-9 Balamuthia mandrillaris is an emerging cause of subacute granulomatous amebic encephalitis (GAE). The diagnosis of this infection has proven to be difficult and is usually made postmortem. Early recognition and treatment may offer some benefit. This report describes a previously healthy woman who died from GAE due to B. mandrillaris. |
Fulminant and fatal encephalitis caused by Acanthamoeba in a kidney transplant recipient: case report and literature review
Satlin MJ , Graham JK , Visvesvara GS , Mena H , Marks KM , Saal SD , Soave R . Transpl Infect Dis 2013 15 (6) 619-26 Acanthamoeba is the most common cause of granulomatous amebic encephalitis, a typically fatal condition that is classically described as indolent and slowly progressive. We report a case of Acanthamoeba encephalitis in a kidney transplant recipient that progressed to death within 3 days of symptom onset and was diagnosed at autopsy. We also review clinical characteristics, treatments, and outcomes of all published cases of Acanthamoeba encephalitis in solid organ transplant (SOT) recipients. Ten cases were identified, and the infection was fatal in 9 of these cases. In 6 patients, Acanthamoeba presented in a fulminant manner and death occurred within 2 weeks after the onset of neurologic symptoms. These acute presentations are likely related to immunodeficiencies associated with solid organ transplantation that result in an inability to control Acanthamoeba proliferation. Skin lesions may predate neurologic involvement and provide an opportunity for early diagnosis and treatment. Acanthamoeba is an under-recognized cause of encephalitis in SOT recipients and often presents in a fulminant manner in this population. Increased awareness of this disease and its clinical manifestations is essential to attain an early diagnosis and provide the best chance of cure. |
Concurrent parasitic infections in a renal transplant patient
Visvesvara GS , Arrowood MJ , Qvarnstrom Y , Sriram R , Bandea R , Wilkins PP , Farnon E , Weitzman G . Emerg Infect Dis 2013 19 (12) 2044-5 Protozoan pathogens, including Entamoeba histolytica, Giardia, Cryptosporidium, Cyclospora, Cystoisospora, and microsporidia such as Enterocytozoon bieneusi, are well-known agents of diarrhea and a major public health problem in developing countries. Infection with Cyclospora cayetanensis and E. bieneusi can occur in immunocompromised and immunocompetent persons. Severe diarrhea and weight loss along with anorexia, nausea, and low-grade fever occur in immunocompromised persons, particularly those with HIV/AIDS and transplant recipients who are taking immunosuppressive drugs (1,2). However, transient diarrhea occurs in immunocompetent persons, notably in travelers returning from countries with poor hygienic standards (1–3). | | We report on a kidney transplant recipient who had uncontrollable diarrhea and weight loss in whom C. cayetanensis and E. bieneusi were detected in biopsy specimens; the diarrhea resolved after treatment with drugs that act specifically on these 2 parasites. The patient was a 55-year-old man from the Dominican Republic living in New York, NY, USA; he had a history of long-term diabetes, coronary disease, and alcoholism. He had undergone a cadaveric renal transplant 14 months earlier and had an uneventful posttransplant course. After returning from visiting family in the Dominican Republic, he sought treatment for acute, profuse watery diarrhea in early November, 2009. He had >10 watery bowel movements daily that were associated with a 20-lb weight loss. His symptoms persisted for 2 months, and he required 2 hospitalizations for the diarrhea. |
Risk for transmission of Naegleria fowleri from solid organ transplantation
Roy SL , Metzger R , Chen JG , Laham FR , Martin M , Kipper SW , Smith LE , Lyon GM 3rd , Haffner J , Ross JE , Rye AK , Johnson W , Bodager D , Friedman M , Walsh DJ , Collins C , Inman B , Davis BJ , Robinson T , Paddock C , Zaki SR , Kuehnert M , DaSilva A , Qvarnstrom Y , Sriram R , Visvesvara GS . Am J Transplant 2013 14 (1) 163-71 Primary amebic meningoencephalitis (PAM) caused by the free-living ameba (FLA) Naegleria fowleri is a rare but rapidly fatal disease of the central nervous system (CNS) affecting predominantly young, previously healthy persons. No effective chemotherapeutic prophylaxis or treatment has been identified. Recently, three transplant-associated clusters of encephalitis caused by another FLA, Balamuthia mandrillaris, have occurred, prompting questions regarding the suitability of extra-CNS solid organ transplantation from donors with PAM. During 1995-2012, 21 transplant recipients of solid organs donated by five patients with fatal cases of PAM were reported in the United States. None of the recipients developed PAM, and several recipients tested negative for N. fowleri by serology. However, historical PAM case reports and animal experiments with N. fowleri, combined with new postmortem findings from four patients with PAM, suggest that extra-CNS dissemination of N. fowleri can occur and might pose a risk for disease transmission via transplantation. The risks of transplantation with an organ possibly harboring N. fowleri should be carefully weighed for each individual recipient against the potentially greater risk of delaying transplantation while waiting for another suitable organ. In this article, we present a case series and review existing data to inform such risk assessments. |
Characterization of a new pathogenic Acanthamoeba species, A. byersi n. sp., isolated from a human with fatal amoebic encephalitis
Qvarnstrom Y , Nerad TA , Visvesvara GS . J Eukaryot Microbiol 2013 60 (6) 626-33 Acanthamoeba spp. are free-living amoebae that are ubiquitous in natural environments. They can cause cutaneous, nasopharyngeal, and disseminated infection, leading to granulomatous amebic encephalitis (GAE) in immunocompromised individuals. In addition, they can cause amoebic keratitis in contact lens wearers. Acanthamoeba GAE is almost always fatal because of difficulty and delay in diagnosis and lack of optimal antimicrobial therapy. Here, we report the description of an unusual strain isolated from skin and brain of a GAE patient. The amoebae displayed large trophozoites and star-shaped cysts, characteristics for acanthamoebas belonging to morphology Group 1. However, its unique morphology and growth characteristics differentiated this new strain from other Group 1 species. DNA sequence analysis, secondary structure prediction, and phylogenetic analysis of the 18S rRNA gene confirmed that this new strain belonged to Group 1, but that it was distinct from the other sequence types within that group. Thus, we hereby propose the establishment of a new species, Acanthamoeba byersi n. sp. as well as a new sequence type, T18, for this new strain. To our knowledge, this is the first report of a Group 1 Acanthamoeba that is indisputably pathogenic in humans. |
Infections with free-living amebae
Visvesvara GS . Handb Clin Neurol 2013 114 153-68 Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri are mitochondria-bearing, free-living eukaryotic amebae that have been known to cause infections of the central nervous system (CNS) of humans and other animals. Several species of Acanthamoeba belonging to several different genotypes cause an insidious and chronic disease, granulomatous amebic encephalitis (GAE), principally in immunocompromised hosts including persons infected with HIV/AIDS. Acanthamoeba spp., belonging to mostly group 2, also cause infection of the human cornea, Acanthamoeba keratitis. Balamuthia mandrillaris causes GAE in both immunocompromised and immunocompetent hosts mostly in the very young or very old individuals. Both Acanthamoeba spp. and B. mandrillaris also cause a disseminated disease including the lungs, skin, kidneys, and uterus. Naegleria fowleri, on the other hand, causes an acute and fulminating, necrotizing infection of the CNS called primary amebic meningoencephalitis (PAM) in children and young adults with a history of recent exposure to warm fresh water. Additionally, another free-living ameba Sappinia pedata, previously described as S. diploidea, also has caused a single case of amebic meningoencephalitis. In this review the biology of these amebae, clinical manifestations, molecular and immunological diagnosis, and epidemiological features associated with GAE and PAM are discussed. |
Primary amebic meningoencephalitis in Florida: a case report and epidemiological review of Florida cases
Budge PJ , Lazensky B , Van Zile KW , Elliott KE , Dooyema CA , Visvesvara GS , Beach MJ , Yoder JS . J Environ Health 2013 75 (8) 26-31 Primary amebic meningoencephalitis (PAM) is a rare but nearly always fatal infection of the central nervous system caused by the thermophilic, free-living ameba Naegleria fowleri. Since its first description in 1965 through 2010, 118 cases have been reported in the U.S.; all cases are related to environmental exposure to warm freshwater; most have occurred in children and adolescents and are associated with recreational water activities, such as swimming, diving, or playing in freshwater lakes, ponds, or rivers. Over one-fourth of all national PAM cases have occurred in Florida. The authors describe here a fatal case of PAM in a resident of northeast Florida and the ensuing environmental and public health investigation; they also provide a review of all cases of PAM in Florida from 1962 to 2010 and discuss public health responses to PAM in Florida, highlighting opportunities for positive collaboration between state and local environmental health specialists, epidemiologists, and the Centers for Disease Control and Prevention. |
Key diagnostic features of granulomatous interstitial nephritis due to Encephalitozoon cuniculi in a lung transplant recipient
Levine DJ , Riley DJ , Jorgensen JH , McClain WD , Tio F , Visvesvara GS , Abboud-Werner SL . Am J Surg Pathol 2013 37 (3) 447-52 Microsporidia are increasingly recognized as opportunistic pathogens in immunocompromised organ transplant recipients (OTR). Disseminated infection due to Encephalitozoon sp. is reported mainly in human immunodeficiency virus (HIV)-positive patients and rarely in HIV-negative OTR. The clinical spectrum ranges from keratoconjunctivitis, to pneumonitis, to acute kidney injury. The kidney is a common site for disseminated infection; however, specialized techniques are required for definitive diagnosis. We report the first case of disseminated Encephalitozoon cuniculi infection in an HIV-negative lung transplant recipient diagnosed on renal biopsy. Five months after transplant, he presented with fever and a lung infiltrate and developed acute kidney injury. Renal biopsy showed granulomatous interstitial nephritis with gram-positive rod-shaped organisms with a "belt-like stripe" in tubular epithelial cells. Electron microscopy, polymerase chain reaction, and mammalian cell cultures of the urine sediment confirmed E. cuniculi infection. Retrospective review of a previous lung biopsy showed similar organisms. On the basis of electron microscopy findings, the patient was treated with albendazole, and immunosuppressive therapy was reduced. However, the patient expired due to Aspergillus pneumonia and disseminated E. cuniculi infection. Microsporidia should be considered in cases of fever of unknown origin and/or multiorgan infection in HIV-negative OTR when other causes have been excluded, as successful treatment requires early detection. |
Primary amebic meningoencephalitis deaths associated with sinus irrigation using contaminated tap water
Yoder JS , Straif-Bourgeois S , Roy SL , Moore TA , Visvesvara GS , Ratard RC , Hill VR , Wilson JD , Linscott AJ , Crager R , Kozak NA , Sriram R , Narayanan J , Mull B , Kahler AM , Schneeberger C , da Silva AJ , Poudel M , Baumgarten KL , Xiao L , Beach MJ . Clin Infect Dis 2012 55 (9) e79-85 BACKGROUND: Naegleria fowleri is a climate-sensitive, thermophilic ameba found in the environment, including warm, freshwater lakes and rivers. Primary amebic meningoencephalitis (PAM), which is almost universally fatal, occurs when N. fowleri-containing water enters the nose, typically during swimming, and N. fowleri migrates to the brain via the olfactory nerve. In 2011, 2 adults died in Louisiana hospitals of infectious meningoencephalitis after brief illnesses. METHODS: Clinical and environmental testing and case investigations were initiated to determine the cause of death and to identify the exposures. RESULTS: Both patients had diagnoses of PAM. Their only reported water exposures were tap water used for household activities, including regular sinus irrigation with neti pots. Water samples, tap swab samples, and neti pots were collected from both households and tested; N. fowleri were identified in water samples from both homes. CONCLUSIONS: These are the first reported PAM cases in the United States associated with the presence of N. fowleri in household plumbing served by treated municipal water supplies and the first reports of PAM potentially associated with the use of a nasal irrigation device. These cases occurred in the context of an expanding geographic range for PAM beyond southern tier states with recent case reports from Minnesota, Kansas, and Virginia. These infections introduce an additional consideration for physicians recommending nasal irrigation and demonstrate the importance of using appropriate water (distilled, boiled, filtered) for nasal irrigation. Furthermore, the changing epidemiology of PAM highlights the importance of raising awareness about this disease among physicians treating persons showing meningitislike symptoms. |
Treatment of granulomatous amoebic encephalitis with voriconazole and miltefosine in an immunocompetent soldier
Webster D , Umar I , Kolyvas G , Bilbao J , Guiot MC , Duplisea K , Qvarnstrom Y , Visvesvara GS . Am J Trop Med Hyg 2012 87 (4) 715-8 A 38-year-old male immunocompetent soldier developed generalized seizures. He underwent surgical debulking and a progressive demyelinating pseudotumor was identified. Serology and molecular testing confirmed a diagnosis of granulomatous amoebic encephalitis caused by Acanthamoeba sp. in this immunocompetent male. The patient was treated with oral voriconazole and miltefosine with Acanthamoeba titers returning to control levels and serial imaging demonstrating resolution of the residual lesion. |
Molecular characterization of Acanthamoeba isolated in water treatment plants and comparison with clinical isolates
Magnet A , Galvan AL , Fenoy S , Izquierdo F , Rueda C , Fernandez Vadillo C , Perez-Irezabal J , Bandyopadhyay K , Visvesvara GS , da Silva AJ , Del Aguila C . Parasitol Res 2012 111 (1) 383-92 A total of 116 samples (44 clinical specimens and 72 environmental samples) have been analyzed for the presence of Acanthamoeba. The environmental samples (ESs) were collected from four drinking water treatment plants (DWTP, n=32), seven wastewater treatment plants (n=28), and six locations of influence (n=12) on four river basins from the central area of Spain (winter-spring 2008). Water samples were concentrated by using the IDEXX Filta-Max((R)) system. Acanthamoeba was identified in 65 of the 72 ESs by culture isolation (90.3%) and 63 by real-time PCR (87.5%), resulting in all sampling points (100%) positive for Acanthamoeba when considering both techniques and all the time period analyzed. Nine of the 44 clinical specimens were positive for Acanthamoeba. Seventeen Acanthamoeba strains (eight from four DWTP and nine from clinical samples) were also established in axenic-PYG medium. Twenty-four of the ESs and the 17 Acanthamoeba sp. strains were genotyped as T4/1, T4/8, and T4/9. The eight strains isolated from the DWTP samples were inoculated in nude mouse to ascertain their potential pathogenicity in this model. Animals that were inoculated died or showed central nervous system symptoms 9 days post-inoculation. Examination of immunofluorescence-stained brain and lung tissue sections showed multiple organisms invading both tissues, and re-isolation of throphozoites was successful in these tissues of all infected animals. For the first time, potentially pathogenic Acanthamoeba T4 has been detected in 100% of different types of water samples including tap water and sewage effluents in the central area of Spain suggesting a potential health threat for humans especially for the contact lens wearers. |
Balamuthia mandrillaris and Acanthamoeba amebic encephalitis with neurotoxoplasmosis coinfection in a patient with advanced HIV infection
Pietrucha-Dilanchian P , Chan JC , Castellano-Sanchez A , Hirzel A , Laowansiri P , Tuda C , Visvesvara GS , Qvarnstrom Y , Ratzan KR . J Clin Microbiol 2012 50 (3) 1128-31 We describe a patient with advanced HIV infection and Balamuthia mandrillaris and Acanthamoeba amebic encephalitis with Toxoplasma gondii coinfection. A multidisciplinary effort and state-of-the-art diagnostic techniques were required for diagnosis. Our patient is the first reported case of an HIV-infected person with dual Balamuthia mandrillaris and Acanthamoeba amebic encephalitis with neurotoxoplasmosis coinfection. |
Fatal Naegleria fowleri infection acquired in Minnesota: possible expanded range of a deadly thermophilic organism
Kemble SK , Lynfield R , Devries AS , Drehner DM , Pomputius WF 3rd , Beach MJ , Visvesvara GS , da Silva AJ , Hill VR , Yoder JS , Xiao L , Smith KE , Danila R . Clin Infect Dis 2012 54 (6) 805-9 BACKGROUND: Primary amebic meningoencephalitis (PAM), caused by the free-living ameba Naegleria fowleri, has historically been associated with warm freshwater exposures at lower latitudes of the United States. In August 2010, a Minnesota resident, aged 7 years, died of rapidly progressive meningoencephalitis after local freshwater exposures, with no history of travel outside the state. PAM was suspected on the basis of amebae observed in cerebrospinal fluid. METHODS: Water and sediment samples were collected at locations where the patient swam during the 2 weeks preceding illness onset. Patient and environmental samples were tested for N. fowleri with use of culture and real-time polymerase chain reaction (PCR); isolates were genotyped. Historic local ambient temperature data were obtained. RESULTS: N. fowleri isolated from a specimen of the patient's brain and from water and sediment samples was confirmed using PCR as N. fowleri genotype 3. Surface water temperatures at the times of collection of the positive environmental samples ranged from 22.1 degrees C to 24.5 degrees C. August 2010 average air temperature near the exposure site was 25 degrees C, 3.6 degrees C above normal and the third warmest for August in the Minneapolis area since 1891. CONCLUSIONS: This first reported case of PAM acquired in Minnesota occurred 550 miles north of the previously reported northernmost case in the Americas. Clinicians should be aware that N. fowleri-associated PAM can occur in areas at much higher latitude than previously described. Local weather patterns and long-term climate change could impact the frequency of PAM. |
Tubulinosema sp. microsporidian myositis in immunosuppressed patient
Choudhary MM , Metcalfe MG , Arrambide K , Bern C , Visvesvara GS , Pieniazek NJ , Bandea RD , Deleon-Carnes M , Adem P , Zaki SR , Saeed MU . Emerg Infect Dis 2011 17 (9) 1727-30 The Phylum Microsporidia comprises >1,200 species, only 15 of which are known to infect humans, including the genera Trachipleistophora, Pleistophora, and Brachiola. We report an infection by Tubulinosema sp. in an immunosuppressed patient. |
Multisystemic infection with an Acanthamoeba sp in a dog
Kent M , Platt SR , Rech RR , Eagleson JS , Howerth EW , Shoff M , Fuerst PA , Booton G , Visvesvara GS , Schatzberg SJ . J Am Vet Med Assoc 2011 238 (11) 1476-81 CASE DESCRIPTION: A 10-month-old Boxer was evaluated for fever and signs of cervical pain. CLINICAL FINDINGS: Physical examination revealed lethargy, fever, and mucopurulent ocular and preputial discharge. On neurologic examination, the gait was characterized by a short stride. The dog kept its head flexed and resisted movement of the neck, consistent with cervical pain. Clinicopathologic findings included neutrophilic leukocytosis, a left shift, and monocytosis. Cervical radiographs were unremarkable. Cerebrospinal fluid analysis revealed neutrophilic pleocytosis and high total protein content. On the basis of signalment, history, and clinicopathologic data, a diagnosis of steroid-responsive meningitis-arteritis was made. TREATMENT AND OUTCOME: The dog was treated with prednisone (3.2 mg/kg [1.45 mg/lb], PO, q 24 h), for 3 weeks with limited response. Consequently, azathioprine (2 mg/kg [0.9 mg/lb], PO, q 24 h) was administered. Three weeks later, the dog was evaluated for tachypnea and lethargy. Complete blood count revealed leukopenia, neutropenia, and a left shift. Thoracic radiography revealed a diffuse bronchointerstitial pattern. The dog subsequently went into respiratory arrest and died. On histologic evaluation, amoebic organisms were observed in the lungs, kidneys, and meninges of the brain and spinal cord. A unique Acanthamoeba sp was identified by use of PCR assay. CLINICAL RELEVANCE: This dog developed systemic amoebic infection presumed to be secondary to immunosuppression. The development of secondary infection should be considered in animals undergoing immunosuppression for immune-mediated disease that develop clinical signs unrelated to the primary disease. Although uncommon, amoebic infection may develop in immunosuppressed animals. Use of a PCR assay for identification of Acanthamoeba spp may provide an antemortem diagnosis. |
Identification of antigenic targets for immunodetection of Balamuthia mandrillaris infection
Kucerova Z , Sriram R , Wilkins PP , Visvesvara GS . Clin Vaccine Immunol 2011 18 (8) 1297-301 The free-living amoeba Balamuthia mandrillaris causes granulomatous amoebic encephalitis (GAE) in humans. Rapid identification of balamuthiasis is critical for effective therapeutic intervention and case management. In the present study we identified target antigens for development of a serologic assay for B. mandrillaris infection. We demonstrated by silver staining that protein profiles for all eight isolates of B. mandrillaris, independent of human or animal origin or geographic origin, appeared to be similar except for some minor differences, indicating the molecular homogeneity of these strains. The profiles of all isolates ranged from 200 to 10 kDa were similar with a prominent protein visible around 30 kDa; all appeared considerably different from protein profiles of the control E6 cells, Acanthamoeba, and Naegleria isolates. Western blot analysis with rabbit hyperimmune serum identified the major immunodominant antigens of 25, 50, 75 and 80 kDa; positive human sera reacted strongly with proteins around 25, 40, 50 and 75 kDa. Proteins around 40 kDa detected by human serum were not recognized by hyperimmune rabbit serum. None of the target proteins were detected by uninfected control sera. Reactivities of five patients sera with 4 different isolates of B. mandrillaris (two strains of human and two strains of animal origins) revealed that patients' sera reacted slightly differently with different B. mandrillaris isolates, although major proteins of approximately 25, 50 and 75kDa were present in all extracts. |
Primary amebic meningoencephalitis caused by Naegleria fowleri, Karachi, Pakistan
Shakoor S , Beg MA , Mahmood SF , Bandea R , Sriram R , Noman F , Ali F , Visvesvara GS , Zafar A . Emerg Infect Dis 2011 17 (2) 258-61 We report 13 cases of Naegleria fowleri primary amebic meningoencephalitis in persons in Karachi, Pakistan, who had no history of aquatic activities. Infection likely occurred through ablution with tap water. An increase in primary amebic meningoencephalitis cases may be attributed to rising temperatures, reduced levels of chlorine in potable water, or deteriorating water distribution systems. |
Prevalence of Acanthamoeba spp. and other free-living amoebae in household water, Ohio, USA-1990-1992
Stockman LJ , Wright CJ , Visvesvara GS , Fields BS , Beach MJ . Parasitol Res 2010 108 (3) 621-7 Knowledge of the prevalence of free-living amoebae (FLA) in US household water can provide a focus for prevention of amoeba-associated illnesses. Household water samples from two Ohio counties, collected and examined for amoebae during 1990-1992, were used to describe the prevalence of Acanthamoeba and other FLA in a household setting. Amoebae were isolated and identified by morphologic features. A total of 2,454 samples from 467 households were examined. Amoebae were found in water samples of 371 (79%) households. Sites most likely to contain amoeba were shower heads (52%) and kitchen sprayers (50%). Species of Hartmannella, Acanthamoeba, or Vahlkampfia were most common. Detection was higher in biofilm swab samples than in water samples. Detection of FLA and Acanthamoeba, at 79% and 51%, respectively, exceed estimates that have been published in previous surveys of household sources. We believe FLA are commonplace inhabitants of household water in this sample as they are in the environment. |
Multiplex assay detection of immunoglobulin G antibodies that recognize Giardia intestinalis and Cryptosporidium parvum antigens
Priest JW , Moss DM , Visvesvara GS , Jones CC , Li A , Isaac-Renton JL . Clin Vaccine Immunol 2010 17 (11) 1695-707 Giardiasis and cryptosporidiosis are common enteric parasitic diseases that have similar routes of transmission. In this work, we have identified epitopes within the Giardia variant-specific surface protein (VSP) sequences that are recognized by IgG antibodies from 13/14 (93%) stool-confirmed giardiasis patient sera. The conserved epitopes are shared among VSPs from both of the assemblages that commonly infect humans, and they are likely to be structural as both sodium dodecylsulfate treatment and dithiothreitol reduction decrease antibody recognition. In a multiplex bead assay (MBA), we have used three VSP fragments from an Assemblage A Giardia strain, three VSP fragments from Assemblage B strains, and the alpha-1 giardin structural antigen to detect IgG antibodies to Giardia and have used the recombinant 17- and 27-kDa antigens to simultaneously detect IgG antibodies to Cryptosporidium. The MBA differentiated between sera from Giardia and Cryptosporidium outbreaks and also identified a giardiasis outbreak that may have included cryptosporidiosis cases. Approximately 40% of cryptosporidiosis outbreak samples had high MBA responses for both the 27- and 17-kDa antigens, while <10% of non-outbreak and giardiasis outbreak samples were high responders. At least 60% of giardiasis outbreak samples were positive for antibodies to multiple Giardia antigens, while ≤12% of non-outbreak samples and samples from US and British Columbia cryptosporidiosis outbreaks met our definition for Giardia seropositivity. MBA using multiple parasite antigens may prove useful in the epidemiologic analysis of future waterborne or foodborne outbreaks of diarrheal disease. |
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