FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1506487234> ?p ?o ?g. }

• W1506487234 endingPage "2167" @default.
• W1506487234 startingPage "2153" @default.
• W1506487234 abstract "In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virus infection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease. In 1998, an outbreak of acute encephalitis with high mortality rates among pig handlers in Malaysia led to the discovery of a novel paramyxovirus named Nipah virus. A multidisciplinary investigation that included epidemiology, microbiology, molecular biology, and pathology was pivotal in the discovery of this new human infection. Clinical and autopsy findings were derived from a series of 32 fatal human cases of Nipah virus infection. Diagnosis was established in all cases by a combination of immunohistochemistry (IHC) and serology. Routine histological stains, IHC, and electron microscopy were used to examine autopsy tissues. The main histopathological findings included a systemic vasculitis with extensive thrombosis and parenchymal necrosis, particularly in the central nervous system. Endothelial cell damage, necrosis, and syncytial giant cell formation were seen in affected vessels. Characteristic viral inclusions were seen by light and electron microscopy. IHC analysis showed widespread presence of Nipah virus antigens in endothelial and smooth muscle cells of blood vessels. Abundant viral antigens were also seen in various parenchymal cells, particularly in neurons. Infection of endothelial cells and neurons as well as vasculitis and thrombosis seem to be critical to the pathogenesis of this new human disease. An outbreak of a previously unrecognized paramyxovirus infection that caused an encephalitic syndrome mainly among pig handlers occurred in Malaysia and Singapore in late 1998 and early 1999.1Centers for Disease Control and Prevention Outbreak of Hendra-like virus-Malaysia and Singapore, 1998–1999.MMWR Morb Mortal Wkly Rep. 1999; 48: 265-269PubMed Google Scholar, 2Chua KB Goh KJ Wong KT Kamarulzaman A Tan PS Ksiazek TG Zaki SR Paul G Lam SK Tan CT Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia.Lancet. 1999; 354: 1257-1259Abstract Full Text Full Text PDF PubMed Scopus (543) Google Scholar In Malaysia, the outbreak seemed to have started around pig farms in Ipoh, in the state of Perak, and was spread by the movement of sick pigs to a second epicenter ∼160 miles south in the state of Negri Sembilan.1Centers for Disease Control and Prevention Outbreak of Hendra-like virus-Malaysia and Singapore, 1998–1999.MMWR Morb Mortal Wkly Rep. 1999; 48: 265-269PubMed Google Scholar Later, the infection spread to workers in an abattoir in Singapore, where pigs originating from Negri Sembilan were held and slaughtered.3Paton NI Leo YS Zaki SR Auchus AP Lee KE Ling AE Chew SK Ang B Rollin PE Umapathi T Sng I Lee CC Lim E Ksiazek TG Outbreak of Nipah-virus infection among abattoir workers in Singapore.Lancet. 1999; 354: 1253-1256Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 4Tambyah PA Tan JH Ong BK Ho KH Chan KP First case of Nipah virus encephalitis in Singapore.Intern Med J. 2001; 31: 132-133Crossref PubMed Google Scholar There were 105 deaths among 265 reported cases of encephalitis, a mortality rate of nearly 40%.5Parashar UD Sunn LM Ong F Mounts AW Arif MT Ksiazek TG Kamaluddin MA Mustafa AN Kaur H Ding LM Othman G Radzi HM Kitsutani PT Stockton PC Arokiasamy J Gary Jr, HE Anderson LJ Case-control study of risk factors for human infection with a new zoonotic paramyxovirus, Nipah virus, during a 1998–1999 outbreak of severe encephalitis in Malaysia.J Infect Dis. 2000; 181: 1755-1759Crossref PubMed Scopus (204) Google Scholar Most patients presented with a severe acute encephalitic syndrome, but some also had significant pulmonary manifestations.3Paton NI Leo YS Zaki SR Auchus AP Lee KE Ling AE Chew SK Ang B Rollin PE Umapathi T Sng I Lee CC Lim E Ksiazek TG Outbreak of Nipah-virus infection among abattoir workers in Singapore.Lancet. 1999; 354: 1253-1256Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 6Goh KJ Tan CT Chew NK Tan PS Kamarulzaman A Sarji SA Wong KT Abdullah BJ Chua KB Lam SK Clinical features of Nipah virus encephalitis among pig farmers in Malaysia.N Engl J Med. 2000; 342: 1229-1235Crossref PubMed Scopus (361) Google Scholar, 7Lee KE Umapathi T Tan CB Tjia HT Chua TS Oh HM Fock KM Kurup A Das A Tan AK Lee WL The neurological manifestations of Nipah virus encephalitis, a novel paramyxovirus.Ann Neurol. 1999; 46: 428-432Crossref PubMed Scopus (86) Google Scholar A syncytium-forming virus was isolated from the cerebrospinal fluid (CSF) of several patients. Electron microscopy (EM) examination revealed an enveloped virus with filamentous nucleocapsids, which when negatively stained showed a herringbone structure, characteristic of the family Paramyxoviridae.8Chua KB Bellini WJ Rota PA Harcourt BH Tamin A Lam SK Ksiazek TG Rollin PE Zaki SR Shieh W Goldsmith CS Gubler DJ Roehrig JT Eaton B Gould AR Olson J Field H Daniels P Ling AE Peters CJ Anderson LJ Mahy BW Nipah virus: a recently emergent deadly paramyxovirus.Science. 2000; 288: 1432-1435Crossref PubMed Scopus (882) Google Scholar Reactivity of infected culture cells and tissues from fatal cases with anti-Hendra antibodies by immunofluorescence and immunohistochemistry (IHC) as well as detection of anti-Hendra IgM antibodies in the serum and CSF suggested the possibility of Hendra or Hendra-like virus infection.1Centers for Disease Control and Prevention Outbreak of Hendra-like virus-Malaysia and Singapore, 1998–1999.MMWR Morb Mortal Wkly Rep. 1999; 48: 265-269PubMed Google Scholar Preliminary autopsy findings showed that the central nervous system (CNS) seemed to be a major target.2Chua KB Goh KJ Wong KT Kamarulzaman A Tan PS Ksiazek TG Zaki SR Paul G Lam SK Tan CT Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia.Lancet. 1999; 354: 1257-1259Abstract Full Text Full Text PDF PubMed Scopus (543) Google Scholar, 3Paton NI Leo YS Zaki SR Auchus AP Lee KE Ling AE Chew SK Ang B Rollin PE Umapathi T Sng I Lee CC Lim E Ksiazek TG Outbreak of Nipah-virus infection among abattoir workers in Singapore.Lancet. 1999; 354: 1253-1256Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 8Chua KB Bellini WJ Rota PA Harcourt BH Tamin A Lam SK Ksiazek TG Rollin PE Zaki SR Shieh W Goldsmith CS Gubler DJ Roehrig JT Eaton B Gould AR Olson J Field H Daniels P Ling AE Peters CJ Anderson LJ Mahy BW Nipah virus: a recently emergent deadly paramyxovirus.Science. 2000; 288: 1432-1435Crossref PubMed Scopus (882) Google Scholar Viral genomic sequencing provided evidence that this previously unknown virus is related to, but distinct from, Hendra virus.8Chua KB Bellini WJ Rota PA Harcourt BH Tamin A Lam SK Ksiazek TG Rollin PE Zaki SR Shieh W Goldsmith CS Gubler DJ Roehrig JT Eaton B Gould AR Olson J Field H Daniels P Ling AE Peters CJ Anderson LJ Mahy BW Nipah virus: a recently emergent deadly paramyxovirus.Science. 2000; 288: 1432-1435Crossref PubMed Scopus (882) Google Scholar, 9Harcourt BH Tamin A Ksiazek TG Rollin PE Anderson LJ Bellini WJ Rota PA Molecular characterization of Nipah virus, a newly emergent paramyxovirus.Virology. 2000; 271: 334-349Crossref PubMed Scopus (239) Google Scholar The virus was subsequently named Nipah virus after Kampung Sungai Nipah (Nipah River Village), where the first viral isolates were obtained.7Lee KE Umapathi T Tan CB Tjia HT Chua TS Oh HM Fock KM Kurup A Das A Tan AK Lee WL The neurological manifestations of Nipah virus encephalitis, a novel paramyxovirus.Ann Neurol. 1999; 46: 428-432Crossref PubMed Scopus (86) Google Scholar, 10Centers for Disease Control and Prevention Update: outbreak of Nipah virus—Malaysia and Singapore, 1999.MMWR Morb Mortal Wkly Rep. 1999; 48: 335-337PubMed Google Scholar This study is based on the clinical and autopsy findings for 32 patients who died of Nipah virus infection. We examined the relative usefulness of various laboratory tests, including IHC, serology, and virus isolation, for the diagnosis of this emerging infectious disease. We also describe the pathological findings, including EM and tissue immunolocalization of viral antigens, and discuss the pathogenesis of Nipah virus infection based on these findings. A series of 32 fatal cases of Nipah infection, which comprised all of the cases autopsied from late 1998 to mid-1999, was drawn from five hospitals in Malaysia. Fifteen cases were from the Seremban hospital (Table 1, cases 1 to 15); three from the Kuala Lumpur hospital (cases 16 to 18); nine from the Ipoh hospital (cases 19 to 27); four from the University of Malaya Medical Center, Kuala Lumpur (cases 28 to 31); and one from the Kelang hospital (case 32). Medical records from the various hospitals were systematically reviewed, and demographic, clinical, and other data were extracted.Table 1Thirty-Two Fatal Cases of Nipah Virus Infection: Available Clinical and Laboratory DataSerologyCSFSerumCase no.Age (year/sex)Prodrome (no. days)Total duration of illness (no. days)IgMIgGIgMIgGVirus isolationIHC141/M310ndnd+−++252/M68−−+−++324/M57−−+−++465/M26−−+−nd+522/M48ndnd+−++627/M410ndnd+−nd+754/M12+−+−nd+830/M46+−+−nd+942/M56ndnd+−++1046/M16+−++nd+1120/M411+−++nd+1271/M37+−++nd+1349/M27+−+−nd+1444/M514+−ndndnd−1513/F25ndndndndnd+1636/M36−−ndndnd+1750/F33−−+−nd+1849/F37ndnd+−nd+1954/M431ndnd++nd−2039/M317ndnd++nd−2146/M23ndnd+−nd+2237/M47ndnd+−nd+2353/M13ndnd+−nd+2451/M79+++−nd+2529/M38ndnd+−nd+2655/M225+++−nd+2775/M24ndnd−−nd+2851/M37+−+−++2952/M711+++−++3034/M38+−−−nd+3131/M234++−−−−3226/M*Patient with relapse encephalitis who had onset of symptoms a few months before last hospital admission. Duration of illness for admission was 11 days.*Patient with relapse encephalitis who had onset of symptoms a few months before last hospital admission. Duration of illness for admission was 11 days.ndnd−+nd+Positive, +; negative, −; nd, not done.Prodrome, onset of fever to admission. Total duration of illness, onset of fever to death.* Patient with relapse encephalitis who had onset of symptoms a few months before last hospital admission. Duration of illness for admission was 11 days. Open table in a new tab Positive, +; negative, −; nd, not done. Prodrome, onset of fever to admission. Total duration of illness, onset of fever to death. Of the 32 autopsies, 29 were full autopsies and 3 were limited to the brain. Tissues were fixed in 10% buffered formalin, paraffin-embedded, and stained with hematoxylin and eosin (H&E). The antibody initially used for Nipah viral antigen detection was anti-Hendra hyperimmune mouse ascitic fluid [Centers for Disease Control and Prevention (CDC), Atlanta, GA]. Subsequently, hyperimmune mouse ascitic fluid against Nipah virus was generated at the CDC and reactivity was compared with that of the mouse anti-Hendra antibody. The specificity and sensitivity of these antibodies in the IHC analyses were tested by using Vero E6 cells (Vero clone CRL 1586; American Type Culture Collection, Rockville, MD) that were uninfected or infected with Hendra or Nipah virus. Antibody specificities were further confirmed by testing specimens from patients with Japanese encephalitis (JE), measles, eastern equine encephalitis, enterovirus71, or influenza, and tissue culture cells infected with western equine encephalitis virus, measles virus, or La Crosse encephalitis viruses. Negative antibody controls for each slide in the IHC analysis included replacing primary antibody with normal mouse ascitic fluid or with the primary antibody absorbed with Nipah virus antigens. Because there was a high initial suspicion of JE, specimens from all patients were also stained for JE viral antigens by using a cross-reactive anti-flavivirus antibody. Tissue blocks were chosen for IHC analysis after slides of the H&E-stained specimens were reviewed. The IHC was based on a method described previously for hantavirus.11Zaki SR Greer PW Coffield LM Goldsmith CS Nolte KB Foucar K Feddersen RM Zumwalt RE Miller GL Khan AS Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease.Am J Pathol. 1995; 146: 552-579PubMed Google Scholar Briefly, 4-μm sections were deparaffinized and rehydrated through graded alcohol and distilled water. They were predigested by 0.1 mg/ml of proteinase K (Boehringer-Mannheim Corp., Indianapolis, IN) in 0.6 mol/L of Tris (pH 7.5)/0.1 CaCl2 for 15 minutes at room temperature and blocked with normal swine serum. Primary antibodies were applied for 1 hour at room temperature. Optimal conditions for primary antibody and digestion conditions were previously determined by titration experiments. For anti-Hendra and anti-Nipah antibodies, the dilutions were 1:4000 and 1:2000, respectively. This step was followed by sequential application of biotinylated link antibody, alkaline phosphatase-conjugated streptavidin, and napthol fast red according to the manufacturer's protocol (LSAB2 Universal Alkaline Phosphatase Kit; DAKO Corporation, Carpinteria, CA). Sections were then counterstained in Meyer's hematoxylin (Fisher Scientific, Pittsburgh, PA) and mounted with an aqueous mounting medium (Faramount; DAKO Corporation). Specimens from all cases were tested with anti-Hendra antibody and selected cases with anti-Nipah antibody. Formalin-fixed brain tissues were postfixed with 1% osmium tetroxide in 0.1 mol/L of phosphate buffer, en bloc stained with 4% aqueous uranyl acetate, dehydrated through a graded series of alcohols and propylene oxide, and embedded in a mixture of epon substitute and Araldite.12Mollenhauer HH Plastic embedding mixtures for use in electron microscopy.Stain Technol. 1964; 39: 111-114PubMed Google Scholar Ultrathin sections were stained with 4% uranyl acetate and Reynolds' lead citrate. IgM and IgG antibodies to Nipah virus in patients were detected by enzyme-linked immunosorbent assay using cross-reactive inactivated Hendra virus antigens. Both tests followed methods previously described for Ebola virus.13Ksiazek TG Rollin PE Williams AJ Bressler DS Martin ML Swanepoel R Burt FJ Leman PA Khan AS Rowe AK Mukunu R Sanchez A Peters CJ Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995.J Infect Dis. 1999; 179: S177-S187Crossref PubMed Scopus (301) Google Scholar In brief, the IgM assay was performed in a Mu-capture format and used Hendra antigens obtained from virus-infected γ-irradiated Vero E6 cells and anti-Hendra hyperimmune mouse ascitic fluid antibody. The IgG assay used a detergent-extracted Hendra antigen obtained from infected Vero E6 cells and inactivated by γ irradiation; antigen was adsorbed directly onto microtiter plates. Control IgG and IgM assays were also performed with antigens from mock-infected Vero E6 cells. The IgM-capture assay used goat anti-human Mu to capture IgM (Biosource, Camarilla, CA) and a horseradish peroxidase-conjugated goat anti-mouse IgG (Biosource). The IgG assay used a horseradish peroxidase-conjugated mouse anti-human γ-chain-specific antibody (Accurate Chemical, Westbury, NY) to detect bound IgG. Sera were tested in a fourfold dilution series from 1:100 to 1:6400, and CSF was similarly tested in a fourfold series from 1:20 to 1:1280. A sample of negative donors was used to validate the cutoff values for the assays. Samples were considered positive for the IgM assay if the sum of the adjusted optical densities from all of the dilutions (infected antigen less the mock-infected antigen) was >0.45 through the entire dilution series and the titer was ≥1:400 (1:16 for CSF). Samples were likewise considered positive in the IgG assay if the sum for the adjusted optical densities from all of the dilutions (infected antigen less the mock-infected antigen) was >0.90 through the entire dilution series and the titer was ≥1:400 (≥1:80 for CSF). Virus isolation and identification were attempted with specimens from eight patients by use of a previously described method.14Chua KB Lam SK Goh KJ Hooi PS Ksiazek TG Kamarulzaman A Olson J Tan CT The presence of Nipah virus in respiratory secretions and urine of patients during an outbreak of Nipah virus encephalitis in Malaysia.J Infect. 2001; 42: 40-43Abstract Full Text PDF PubMed Scopus (115) Google Scholar In brief, 100 μl of CSF was innoculated on previously seeded wells with 105 Vero cells (CCL-81; American Type Culture Collection); and the cells were transferred to 1 ml of Eagle's minimal essential growth medium containing 10% fetal calf serum (Flowlab, Sydney, Australia). After incubation at 37°C, positive identification of virus was made by immunofluorescence using anti-Hendra hyperimmune mouse ascitic fluid and goat anti-mouse IgG fluorescein-isothiocyanate conjugate (Sigma, St. Louis, MO) secondary antibody. The age of patients in this study ranged from 13 to 75 years (mean, 43 years; median, 44 years) and the male-to-female ratio was 29:3. The prodrome, defined as the time from fever onset to the day of hospital admission, averaged 3.3 days (range, 1 to 7 days) (Table 1). The duration of illness, defined as the time from fever onset to death, averaged 9.5 days (range, 2 to 34 days). Four patients survived >14 days before death. Case 32 had a similar clinical illness a few months earlier, improved, but subsequently relapsed and died. Clinical symptoms and signs are summarized in Table 2. All patients had fever. More than 70% of patients complained of drowsiness, headache, and disorientation or confusion. The most frequent clinical sign among patients was reduced consciousness. Case 31 was recovering in the hospital ward when he developed massive fatal intracerebral hemorrhage.Table 2Frequency of Clinical Symptoms and Signs in 32 Fatal Cases of Nipah Virus Infection%Symptoms Fever100 Drowsiness88 Headache82 Disorientation/confusion76 Giddiness61 Myalgia54 Cough/Respiratory symptoms40 Convulsion28 Vomiting19Signs Reduced consciousness89 Segmental myoclonus50 Hyporeflexia/areflexia50 Seizure40 Cranial nerve palsy29 Pyramidal signs21 Nystagamus/cerebellar signs17 Meningism10 Dysphasia5 Open table in a new tab The macroscopic features were nonspecific. In the CNS, lesions were generally difficult to identify; however, in a few cases, small, discrete, occasionally hemorrhagic, necrotic lesions were found. Only 2 of 10 brains examined showed unequivocal herniation. Case 29 had cerebellar tonsil herniation, and case 31 had uncal herniation and showed a large intracerebral clot in the frontal lobe with intraventricular extension and Duret hemorrhages in the midbrain and pons. Histopathological changes were seen in the blood vessels and parenchyma of multiple organs and are presented accordingly. The distribution of histopathological lesions and immunostaining is shown in Table 3. Extensive involvement of blood vessels in the CNS, lung, heart, and kidney was observed in Nipah virus infection. However, blood vessels in the CNS were the most severely involved. Typically, small arteries, arterioles, capillaries, and venules showed evidence of vasculitis. Vasculitis was not found in medium-sized vessels (eg, renal artery and vein, anterior, and middle cerebral arteries) or large arteries (eg, aorta and pulmonary trunk). No vasculitis was found in the relapse encephalitis case (case 32; Table 1).Table 3Fatal Nipah Virus Infection: Frequency of Necrosis, Vasculitis, and Immunostaining of Viral Antigens in Major OrgansPathologic findingsBrain no. (%)Lung no. (%)Heart no. (%)Kidney no. (%)Spleen no. (%)Necrosis*Necrosis was in the form of parenchymal necrotic plaques in brain, fibrinoid alveolar necrosis in lung, and fibrinoid glomerular necrosis in kidney. In the spleen, acute necrotic inflammation was found in the area of the periarteriolar lymphoid sheath.28/3017/291/2910/2910/24(93)(59)(3)(34)(42)Vasculitis24/3018/299/297/290/24(80)(62)(31)(24)(0)Viral antigens27/327/294/246/251/21(84)(24)(17)(24)(5)Note: The percentage of cases involved was calculated by using as the numerator the number of cases with one or more findings. The denominator is the total number of cases for which tissues were available for study.* Necrosis was in the form of parenchymal necrotic plaques in brain, fibrinoid alveolar necrosis in lung, and fibrinoid glomerular necrosis in kidney. In the spleen, acute necrotic inflammation was found in the area of the periarteriolar lymphoid sheath. Open table in a new tab Note: The percentage of cases involved was calculated by using as the numerator the number of cases with one or more findings. The denominator is the total number of cases for which tissues were available for study. Vasculitis was characterized by various degrees of segmental endothelial destruction, mural necrosis, and karyorrhexis (Figure 1; A to D). Mural necrosis often appeared fibrinoid. Inflammatory cell infiltration of vascular walls by neutrophils and mononuclear cells was usually focal and either partial or transmural (Figure 1, A and B). Thrombosis was found in both inflamed and noninflamed vessels (Figure 1C). Necrosis and hemorrhage adjacent to vasculitic or thrombotic vessels were frequently seen (Figure 1E). Syncytial or multinucleated giant endothelial cells were seen in blood vessels of various organs (Figure 1; B, E, F, and G). In the CNS, they were found in 27% of the cases (Table 4), mostly in patients whose duration of illness ranged from 6 to 15 days (Figure 2). The syncytia typically consisted of several overlapping or sharply molded nuclei with moderate to abundant cytoplasm (Figure 1F). Occasionally, syncytia protruded prominently into the vascular lumen (Figure 1, F and G) and were accompanied by vasculitis (Figure 1B).Table 4Microscopic Features in the Central Nervous System in 30 Fatal Cases of Nipah Virus Infection*Brain tissues from two cases (cases 14 and 15) had severe freezing artifact that precluded adequate histopathologic examination.Histopathologic lesionFrequency, %Necrotic plaque93Perivascular cuffing90Thrombosis87Vasculitis80Parenchymal inflammation67Viral inclusions63Meningitis57Syncytia27* Brain tissues from two cases (cases 14 and 15) had severe freezing artifact that precluded adequate histopathologic examination. Open table in a new tab In the CNS, the main pathological findings were vasculitis, thrombosis, parenchymal necrosis, and presence of viral inclusions (Table 4 and Figure 1, Figure 3, Figure 4, Figure 5). Vascular involvement of gray and white matter was seen throughout the CNS. The spinal cord was examined in eight cases and showed similar pathological lesions in three cases as observed elsewhere in CNS. Pathological lesions similar to those seen elsewhere in CNS were seen in spinal cords of three of eight cases examined. The olfactory bulb was examined in nine cases and did not show any significant histopathology. Common histopathological lesions and their relative frequency in the CNS are summarized in Table 4.Figure 4CNS pathology and viral immunolocalization in Nipah virus infection. A: Well-circumscribed, necrotic plaque associated with a vasculitic and thrombotic arteriole (arrow). B: Higher-power magnification of vessel seen in A showing complete arteriolar obstruction. C: Concentric immunostaining pattern of viral antigens around a necrotic plaque. D and E: High-power magnification showing Nipah virus antigens in neurons and neuronal processes. F: Neuronal body in a microcystic area with positive immunostaining. G: Cells in the white matter are only rarely immunostained. The pencil bundles of Wilson (asterisks) in the putamen are immunonegative even though adjacent neuronal areas are positive. H: Rare glial cell in the white matter showing immunostaining. H&E stain, A and B; immunoalkaline phosphatase with napthol fast red substrate and hematoxylin counterstain, C-H. Original magnifications: ×25 (A); ×100 (B, E); ×12.5 (C); ×158 (D); ×250 (F, H); ×50 (G).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 5CNS pathology and viral immunolocalization in relapse Nipah virus encephalitis (case 32). A: Relapse encephalitis differs from typical acute cases in that the lesions are confluent and geographical in distribution and accompanied with severe neuronal loss and gliosis. B: Numerous Nipah virus antigen-positive macrophages are seen. C: Viral inclusions as seen by IHC; inclusions are usually larger and more abundant than in typical cases. D: Ependymal immunostaining, generally rare in acute Nipah encephalitis, is more prominent in this case. H&E stain, A; immunoalkaline phosphatase with napthol fast red substrate and hematoxylin counterstain, B-D. Original magnifications: ×12.5 (A); ×50 (B); ×158 (C, D).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Plaques with various degrees of necrosis were found in both the gray and white matter (Figure 4A). These necrotic plaques were round or oval with diameters that ranged from ∼0.2 mm to ≥5 mm. Vasculitis, thrombosis, and various degrees of parenchymal edema and inflammation were frequently found in the vicinity of these plaques (Figure 4, A and B). The inflammatory cellular infiltrate consisted of neutrophils, macrophages, lymphocytes, and reactive microglia. Areas of microcystic degeneration were seen, most commonly, in the vicinity of necrotic plaques (Figure 4F). Microcystic change with no adjacent plaques was also occasionally seen. In white matter, damaged axons occasionally formed axonal spheroids similar to those seen in diffuse axonal injury. No large geographic infarctions of the type associated with occlusion of medium-sized or larger arteries were seen. Elsewhere in the parenchyma, focal neuronophagia, microglial nodule formation, and perivascular cuffing (Figure 3, E and F) were seen. Overall, parenchymal inflammation was present in 67% of cases (Table 4). Viral inclusions were found in the cytoplasm and nuclei of neurons, although the latter were generally harder to find. Most inclusions were found near vasculitic vessels or necrotic plaques. Cytoplasmic inclusions were usually small, discrete, eosinophilic, and sometimes multiple (Figure 3A). Nuclear inclusions were less commonly found and occupied most of the nucleus except for a thin rim of chromatin at the periphery (Figure 3C). Although inclusions were found in 63% of cases (Table 4), in many instances they were found in only a few neurons after an extensive search. The CNS pathology in the relapse encephalitis case (case 32; Table 1) was somewhat different from other cases (Figure 5). Viral inclusions were much more extensive and prominent, occupying either the entire neuronal cytoplasm or having a more peripheral distribution; inclusions were also abundant in the neuropil. The parenchymal lesions were larger and more confluent, occasionally hemorrhagic, and associated with severe neuronal loss, gliosis, and abundant macrophages. No vasculitis or typical necrotic plaques were seen and perivascular cuffing was not a prominent feature. In the lung, vasculitis was seen in 62% of cases (Table 3; Figure 1, A and B) and fibrinoid necrosis was found in 59% of cases. Fibrinoid necrosis often involved several adjacent alveoli and was frequently associated with small vessel vasculitis (Table 3, Figure 6A). Multinucleated giant cells with intranuclear inclusions were occasionally noted in alveolar spaces adjacent to necrotic areas (Figure 6; B, C, and D). Alveolar hemorrhage, pulmonary edema, and aspiration pneumonia were often encountered. Histopathological changes of bronchiolar epithelium were uncommon except in one case in which a large bronchus showed severe transmural inflammation and ulceration (case 22; Table 1). The spleen showed white pulp depletion and acute necrotizing inflammation in the periarteriolar sheaths (Figure 7; A, B, and C). In addition, large prominent multinucleated giant cells with intranuclear inclusions were seen in the parenchyma of one case (case 22; Table 1 and Figure 7D). No vasculitis of large blood vessels was seen. Lymph nodes showed large reactive mononuclear cells and occasional necrosis and hemophagocytosis. Rarely, multinucleated giant cells were encountered in cells lining the subcapsular sinusoids of lymph nodes (Figure 7, E and" @default.
• W1506487234 created "2016-06-24" @default.
• W1506487234 creator A5001376315 @default.
• W1506487234 creator A5010843707 @default.
• W1506487234 creator A5014913339 @default.
• W1506487234 creator A5018836842 @default.
• W1506487234 creator A5032897438 @default.
• W1506487234 creator A5038614700 @default.
• W1506487234 creator A5053613915 @default.
• W1506487234 creator A5056132667 @default.
• W1506487234 creator A5060047083 @default.
• W1506487234 creator A5061067183 @default.
• W1506487234 creator A5062809472 @default.
• W1506487234 creator A5063066872 @default.
• W1506487234 creator A5066056273 @default.
• W1506487234 creator A5068016872 @default.
• W1506487234 creator A5069728846 @default.
• W1506487234 creator A5089304162 @default.
• W1506487234 date "2002-12-01" @default.
• W1506487234 modified "2023-10-17" @default.
• W1506487234 title "Nipah Virus Infection" @default.
• W1506487234 cites W1415644738 @default.
• W1506487234 cites W1473677910 @default.
• W1506487234 cites W1513508804 @default.
• W1506487234 cites W1964562460 @default.
• W1506487234 cites W1966849223 @default.
• W1506487234 cites W1966874993 @default.
• W1506487234 cites W1968024319 @default.
• W1506487234 cites W1973647109 @default.
• W1506487234 cites W1978458785 @default.
• W1506487234 cites W1981329413 @default.
• W1506487234 cites W1984844573 @default.
• W1506487234 cites W1986135912 @default.
• W1506487234 cites W2005817713 @default.
• W1506487234 cites W2011937142 @default.
• W1506487234 cites W2016034909 @default.
• W1506487234 cites W2016321962 @default.
• W1506487234 cites W2021734226 @default.
• W1506487234 cites W2037029066 @default.
• W1506487234 cites W2037389800 @default.
• W1506487234 cites W2067235358 @default.
• W1506487234 cites W2076620790 @default.
• W1506487234 cites W2082573664 @default.
• W1506487234 cites W2094644220 @default.
• W1506487234 cites W2114885670 @default.
• W1506487234 cites W2120680145 @default.
• W1506487234 cites W2127949919 @default.
• W1506487234 cites W2128458987 @default.
• W1506487234 cites W2129937430 @default.
• W1506487234 cites W2131714664 @default.
• W1506487234 cites W2132803319 @default.
• W1506487234 cites W2137477090 @default.
• W1506487234 cites W2137504727 @default.
• W1506487234 cites W2141568825 @default.
• W1506487234 cites W2145658128 @default.
• W1506487234 cites W2146499861 @default.
• W1506487234 cites W2146765652 @default.
• W1506487234 cites W2147012515 @default.
• W1506487234 cites W2148775058 @default.
• W1506487234 cites W2150120282 @default.
• W1506487234 cites W2160481471 @default.
• W1506487234 cites W2167508880 @default.
• W1506487234 cites W2169563372 @default.
• W1506487234 cites W2396861040 @default.
• W1506487234 cites W2408020884 @default.
• W1506487234 cites W2408298820 @default.
• W1506487234 cites W2473619339 @default.
• W1506487234 cites W3013474 @default.
• W1506487234 cites W4234694178 @default.
• W1506487234 cites W4237880060 @default.
• W1506487234 cites W4249792547 @default.
• W1506487234 cites W4300803799 @default.
• W1506487234 cites W4302412818 @default.
• W1506487234 cites W4321429509 @default.
• W1506487234 doi "https://doi.org/10.1016/s0002-9440(10)64493-8" @default.
• W1506487234 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1850894" @default.
• W1506487234 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12466131" @default.
• W1506487234 hasPublicationYear "2002" @default.
• W1506487234 type Work @default.
• W1506487234 sameAs 1506487234 @default.
• W1506487234 citedByCount "326" @default.
• W1506487234 countsByYear W15064872342012 @default.
• W1506487234 countsByYear W15064872342013 @default.
• W1506487234 countsByYear W15064872342014 @default.
• W1506487234 countsByYear W15064872342015 @default.
• W1506487234 countsByYear W15064872342016 @default.
• W1506487234 countsByYear W15064872342017 @default.
• W1506487234 countsByYear W15064872342018 @default.
• W1506487234 countsByYear W15064872342019 @default.
• W1506487234 countsByYear W15064872342020 @default.
• W1506487234 countsByYear W15064872342021 @default.
• W1506487234 countsByYear W15064872342022 @default.
• W1506487234 countsByYear W15064872342023 @default.
• W1506487234 crossrefType "journal-article" @default.
• W1506487234 hasAuthorship W1506487234A5001376315 @default.
• W1506487234 hasAuthorship W1506487234A5010843707 @default.
• W1506487234 hasAuthorship W1506487234A5014913339 @default.
• W1506487234 hasAuthorship W1506487234A5018836842 @default.

• next