Pathological and aetiological studies of multifocal interstitial nephritis in wasted pigs at slaughter

Multifocal interstitial nephritis in pigs has been associated with several infectious agents. The objective of the present study was to investigate several different potential infectious agents associated with "white-spotted" kidneys in pigs suffering from wasting at slaughter (aged 6-8 months). Twenty-nine case kidneys (with a "white-spotted" gross appearance) classified into 3 macroscopic lesional grades, and 15 control kidneys (lacking gross lesions), were obtained from a pig abattoir. Laboratory analyses to detect potential associations with the aforementioned pathological condition with Leptospira spp., porcine circovirus type 2 (PCV2), porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus (PRRSV), and bacteria, were carried out. Microscopically, interstitial nephritis with a lymphofollicular inflammatory pattern (follicular nephritis) was observed in both case and control kidneys, with a higher frequency seen in the former ones. No leptospires were identified, although antibodies to the Pomona and Bratislava serovars were detected. Some pyogenic bacteria were also isolated from both case and control kidneys. PCV2 nucleic acid was only detected in 1 case kidney. PRRSV antigen was not found in any tested sample. Some pigs were tested positive for PPV by serology. Apparently, none of the studied agents were specifically associated as being the potential cause of the renal lesions in the studied wasted pigs. The fact that these chronic lesions may have been the consequence of a previous infection with one of these studied microorganisms, or more, and eventually with other non-tested infectious agents during the growing-finishing period, cannot be ruled out.     

Clinical and pathological observations on pigs with postweaning multisystemic wasting syndrome

The aim of this work was to characterise the lesions and agents present in clinically normal and clinically affected pigs on a farm during an outbreak of postweaning multisystemic wasting syndrome (PMWS), and to evaluate the diagnostic techniques for detecting porcine circovirus type 2 (PCV-2) and other microorganisms. Four pigs in the early stage and 11 pigs in the late stage of the disease, and eight clinically normal pigs were necropsied. Samples of lymphoid tissue and serum were also obtained from 12 slaughter pigs from the same farm. The tissues were examined histopathologically, and in situ hybridisation, serology and PCR were used to detect porcine circovirus type 1 (PCV-1) and/or PCV-2 in tissues and/or sera. The presence of porcine reproductive and respiratory syndrome virus (PRRSV), Aujeszky's disease virus (ADV) and porcine parvovirus (PPV) were also investigated. Characteristic microscopical lesions of PMWS were observed in the lymphoid tissues of the pigs in all three necropsied groups; the lesions were most common and severe in the pigs in the early stage of the disease, less so in the pigs in the late stage of the disease, and least in the clinically normal pigs. PCV-2 infection was detected in all the necropsied pigs by in situ hybridisation and PCR. Only three pigs had the PCV-1 genome in serum or lymph node tissue. In contrast, the slaughter pigs had no microscopical lesions and no PCV-2 nucleic acid in their serum or tissues, and only one of them had the pCV-1 genome in its serum. Immunohistochemical, serological and PCR studies revealed that PRRSV and ADV were also present on the farm during the outbreak.     

Viral wasting syndrome of swine: experimental reproduction of postweaning multisystemic wasting syndrome in gnotobiotic swine by coinfection with porcine circovirus 2 and porcine parvovirus

One-day-old gnotobiotic piglets were inoculated intranasally with in vitro passaged porcine circovirus 1 (PCV-1), PCV-2, and porcine parvovirus (PPV) alone or in combination (PCV-1/PCV-2, PCV-1/PPV, and PCV-2/PPV). Piglets were evaluated for 1) the development of porcine postweaning multisystemic wasting syndrome (PMWS), 2) distribution of viral antigens by immunochemistry, and 3) viremia and the presence of viral DNA in nasal and ocular secretions and feces. All single agent-infected piglets and piglets infected with PCV-1/PCV-2 or PCV-1/PPV were clinically asymptomatic. They were transiently viremic and seroconverted to homologous virus(es). At termination of the study on postinfection day (PID) 35, microscopic lesions were restricted to focal inflammatory cell infiltrates in livers and myocardia. One piglet given PCV-1/PPV was PPV viremic for 2 weeks after infection and had lymphangiectasia of the spiral and descending colon associated with granulomatous inflammation. All four PCV-2/PPV-inoculated piglets developed PMWS, characterized by sudden onset of depression and anorexia, icterus, and submucosal edema. One piglet became moribund on PID 27, and the remaining three piglets were euthanatized between PID 27 and PID 30 because of severe disease. Lymph nodes were small and the livers were mottled. Disseminated angiocentric granulomatous inflammation was present in all tissues examined except the brain. Multiple lightly basophilic intracytoplasmic inclusion bodies were identified in macrophages and histiocytes. PCV-2 antigen was widely distributed within macrophages; PPV antigen was sparse. Hepatocellular necrosis and bile retention were prominent. PCV-2 DNA was identified in ocular, fecal, and nasal secretions. Terminal sera contained antibodies to PPV (4/4) and PCV-2 (3/ 4). Production of PMWS in gnotobiotic swine appears to require PCV-2 and additional infectious agents such as PPV for full disease expression in gnotobiotic piglets.     

Detection of Porcine Circovirus Type 2, Porcine Parvovirus and Porcine Pseudorabies Virus from Pigs with Postweaning Multisystemic Wasting Syndrome by Multiplex PCR

Multiplex PCR was established to detect porcine circovirus type 2 (PCV-2), porcine parvovirus (PPV) and porcine pseudorabies virus (PRV) and applied to samples from 137 piglets exhibiting clinical signs of postweaning multisystemic wasting syndrome (PMWS). PCV-2 DNA was detected from all samples. Moreover, 43 samples were positive for PPV but negative for PRV; 11 samples were positive for PRV but negative for PPV; and 35 samples were positive both for PPV and PRV. These results suggests that PCV-2 co-infection with PRV and PPV may play an important role in PMWS. Also, multiplex PCR is an appropriate candidate method for diagnosis of PCV-2, PRV and PPV simultaneously in field cases.     

PRV、PCV-2、PPV多重PCR检测方法的建立及其应用

根据GenBank上已发表的猪伪狂犬病病毒(PRV)、猪Ⅱ型圆环病毒(PCV-2)、猪细小病毒(PPV)核苷酸序列,设计并合成能分别特异性扩增PRV、PCV-2、PPV的引物。经条件优化,建立了同时检测PRV、PCV-2、PPV的多重PCR方法,所扩增特异性产物片段大小分别为217bp、394bp、748bp。该方法不仅特异性强、敏感性高,还克服了对上述病原分别进行检测所带来的诸多弊端,为猪伪狂犬病、猪Ⅱ型圆环病、猪细小病的临床诊断和流行病学调查等研究提供了新手段。     

猪细小病毒、伪狂犬病病毒和猪圆环病毒2型多重PCR检测方法的建立及应用

根据猪细小病毒(PPV)、伪狂犬病病毒(PRV)和猪圆环病毒2型(PCV-2)的基因序列,分别选取各自的保守区段设计引物,通过反应条件的优化,建立了检测PPV、PRV和PCV-2的多重PCR方法.用建立的方法对采自陕西省部分猪场的286份病料及血样进行检测,从对临床健康猪全血样品中PPV、PRV和PCV-2的检测结果看...     

Survey of pigs' kidneys with lesions consistent with PMWS and PDNS and ochratoxicosis. Part 2: pathological and histological findings

One thousand condemned pigs' kidneys were collected in February 2002 from two pig abattoirs in England to assess the lesions due to postweaning multisystemic wasting syndrome (pmws) and porcine dermatitis and nephropathy syndrome (pdns) and the possible contribution of ochratoxicosis; 174 of the kidneys were pale, 295 were swollen and 81 were abnormally firm with the gross appearance of fibrosis. The main macroscopic finding was the presence of multifocal pale cortical lesions, observed in 446 of the kidneys, and there were large cysts in 266 of them. Histopathological lesions of non-suppurative tubulointerstitial nephritis, with degeneration and fibrosis of renal tubules, were identified in 213 of 250 (85.2 per cent) of the kidneys examined. These lesions were consistent with those reported in cases of pmws and pdns. The tubular degeneration and fibrosis were also consistent with ochratoxicosis. A higher mean concentration of ochratoxin A was significantly (P=0.020) associated with the presence of multifocal pale cortical lesions consistent with ochratoxicosis, but a causal relationship was not confirmed because histochemistry was not used to detect ochratoxin in the lesions directly. There was no significant correlation between the microscopic lesions and the concentration of ochratoxin. The degenerative lesions may have been caused by previous exposure to ochratoxin that had subsequently been excreted, but the microscopic lesions also included non-suppurative interstitial nephritis, which was unlikely to have been caused by ochratoxicosis.     

检测PRV野毒株、PCV-2及PPV多重PCR方法的建立及初步应用

根据GenBank中的猪伪狂犬病病毒(PRV)gE、猪圆环病毒2型(PCV-2)ORF2、猪细小病毒(PPV)VP2基因序列,设计了3对引物,成功建立了检测PRV野毒株、PCV-2和PPV的多重PCR诊断方法,扩增产物分别为288 bp、419 bp、681 bp。敏感性、特异性试验结果显示,该PCR对3种病毒的最低核酸检测量分别为PRV 48.2 pg/L、PCV-2 36.7 pg/L、PPV 0.25 ng/L,而PRV(gE基因缺失株)、猪瘟病毒(CSFV)、猪繁殖与呼吸综合征病毒(PRRSV)、大肠杆菌的扩增结果均为阴性。对87份自然感染病猪样品的检测结果表明,该多重PCR检测结果与单一PCR检测结果完全符合。结果表明,该多重PCR方法具有很好的特异性和敏感性,可用于临床PRV野毒株和gE基因缺失疫苗株、PCV-2和PPV的检测。     

Patterns of condemnation rates in swine from a federally inspected abattoir in relation to disease outbreak information in Ontario (2005-2007)

Strong correlations between clinical signs on farms and the presence of lesions at slaughter have been reported. The objective of this study was to determine if changes in condemnation rates provide a data source for surveillance of disease outbreaks in pigs. The data were obtained from 1 abattoir in Ontario (2005-2007). The epidemiological relevance of the results was based on an outbreak of porcine circovirus associated disease (PCVAD) in Ontario in 2005. The total condemnations and condemnations due to arthritis and pneumonia patterns reflected the field infection of PCVAD in 2005 followed by the widespread use of porcine circovirus type 2 (PCV-2) vaccine in 2007. In contrast, increased rates of nephritis and enteritis suggested areas for enhanced surveillance for unexplained changes in disease patterns not identified through traditional passive surveillance. Further studies looking at the benefits of using abattoir data should compare condemnation patterns with multiple sources of swine health data.     

A sequential study of experimental infection of pigs with porcine circovirus and porcine parvovirus: immunostaining of cryostat sections and virus isolation

The sequential tissue distribution of virus was investigated using virus isolation and immunofluorescence tests in 1-day-old piglets inoculated with porcine circovirus 2 (PCV2) and/or porcine parvovirus (PPV). Enlarged mesenteric lymph nodes were seen in the pig inoculated with PCV2 alone and killed at 26 days post-inoculation (PI). One of the pigs inoculated with PCV2 and PPV and killed at 21 days PI had an enlarged liver. The pig killed at 26 days PI in this group had enlarged liver, kidneys and heart. Histopathological changes were seen in lymphoid tissues of the pigs inoculated with PCV2 alone and killed at 14 and 26 days PI. Similar, but more severe, lesions were observed in the pigs infected with PCV2 and PPV and killed from 10 days PI onwards. Histological lesions of nephritis, pneumonia and hepatitis were also apparent in these animals. Mild nephritis was also seen in the pigs infected with PPV alone and killed at 14 and 26 days PI. Moderate amounts of PPV antigen were detected in tissues from the pigs inoculated with PPV alone and killed at 14 days PI. Low levels of PCV antigen were detected, mainly in lymphoid tissues, in the pigs inoculated with PCV alone and killed at 14 days PI. Low to moderate amounts of PCV antigen were detected in a wider range of tissues in the pig in this group killed at 26 days PI. In the pigs inoculated with both viruses, PPV antigen was detected in tissues of pigs killed from 3 to 26 days PI with maximal amounts detected between 6 and 14 days PI. PCV2 antigen was detected in low to moderate amounts in the tissues of pigs killed at 14 days PI. Large amounts of PCV2 antigen were detected in most of the tissues from pigs in this group killed between 17 and 26 days PI. Virus isolation results for PCV2 generally correlated well with the results for immunofluorescent staining. PPV was isolated from almost all tissues from pigs inoculated with PCV2 and PPV, a much higher incidence of positive tissues than observed for immunofluorescent staining.     

山东种公猪精液携带主要病原的检测

采用PCR技术,对2007年-2009年山东部分地区的38个猪场和人工授精站的生产公猪精液样品727份进行了猪瘟病毒(CSFV)、猪繁殖与呼吸综合征病毒(PRRSV)、伪狂犬病病毒(PRV)、猪圆环病毒2型(PCV-2)和猪细小病毒(PPV)5种主要病原的检测。结果检出CSFV、PRRSV、PRV、PCV-2和PPV的阳性数和阳性率分别为18份(2.48%)、27份(3.71%)、7份(0.96%)、33份(4.54%)、9份(1.24%),有7份样品为2种以上病原混合感染,其中以PRRSV+PCV-2混合感染最多。结果表明精液传播病毒仍是当前母猪繁殖障碍的重要原因之一,应重点加强对种公猪的疫病净化和公猪精液管理,从源头控制传染源。     

Effects of the timing of the administration of Mycoplasma hyopneumoniae bacterin on the development of lesions associated with porcine circovirus type 2

To determine whether there is an effect of the timing of vaccination on porcine circovirus type 2 (PCV-2) replication and PCV-2-associated lesions, 78 pigs were randomly assigned to eight groups: group 1 (10 pigs) was vaccinated with a commercial Mycoplasma hyopneumoniae vaccine at two and four weeks of age, group 2 (nine pigs) was vaccinated at four and six weeks of age, group 3 (10 pigs) at six and eight weeks of age and group 4 (10 pigs) at eight and 10 weeks of age; group 5 (nine pigs) was vaccinated once with a double dose at four weeks of age, and group 6 (10 pigs) was vaccinated once with a double dose at eight weeks of age. Groups 7 and 8, both of 10 pigs, were not vaccinated. At eight weeks of age, the pigs in groups 1 to 7 were inoculated with PCV-2. Fourteen days after they had been inoculated, the pigs in groups 1, 4 and 5 had significantly (P<0.05) more copies of the PCV-2 genome in their serum than the unvaccinated pigs. Microscopically, 14 of the 68 inoculated pigs had normal lymphoid tissues, 40 had mild PCV-2-associated lymphoid lesions and 14 had moderate lesions. The mean overall lymphoid lesions (lymphoid depletion, granulomatous inflammation, and quantity of PCV-2 antigen in spleen, tonsil, and five lymph nodes) were significantly (P<0.05) more severe in groups 4 and 5 than in groups 2, 3, 7 and 8.     

Seroprevalence of economically important viral pathogens in swine populations of Trinidad and Tobago,West Indies

The objective of this study was to evaluate the seroprevalence and identify the strains of swine influenza virus (SwIV), as well as the seroprevalence of porcine parvovirus (PPV), transmissible gastroenteritis virus (TGEV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine respiratory coronavirus (PRCV), porcine circovirus type 2 (PCV-2), and classical swine fever virus (CSFV) in pigs in Trinidad and Tobago (T&T). Blood samples (309) were randomly collected from pigs at farms throughout T&T. Serum samples were tested for the presence of antibodies to the aforementioned viruses using commercial ELISA kits, and the circulating strains of SwIV were identified by the hemagglutination inhibition test (HIT). Antibodies against SwIV were detected in 114 out of the 309 samples (37%). Out of a total of 26 farms, 14 tested positive for SwIV antibodies. HI testing revealed high titers against the A/sw/Minnesota/593/99 H3N2 strain and the pH1N1 2009 pandemic strain. Antibodies against PPV were detected in 87 out of the 309 samples (28%), with 11 out of 26 farms testing positive for PPV antibodies. Antibodies against PCV-2 were detected in 205 out of the 309 samples tested (66%), with 25 out of the 26 farms testing positive for PCV-2 antibodies. No antibodies were detected in any of the tested pigs to PRRSV, TGEV, PRCV, or CSFV.     

Experimental infection of 3-week-old conventional colostrum-fed pigs with porcine circovirus type 2 and porcine parvovirus

This report describes an experimental infection with porcine circovirus type 2 (PCV2) in combination with porcine parvovirus (PPV) in 3-week-old conventional colostrum-fed pigs with maternal antibodies to both viruses. Two groups of four pigs each were inoculated with PCV2 and PPV. One of the groups received also a commercial inactivated vaccine against porcine pleuropneumonia to evaluate possible effects of the stimulation of the immune system of pigs on the infection. Another group of four pigs was kept as uninfected control. Clinical signs, rectal temperatures and body weights were recorded. Serum antibody titers to PCV2 and PPV were determined at weekly intervals. Pigs were killed 42 days after inoculation and tissue samples were examined for the presence of gross and microscopic lesions. Tissues were also analyzed for the presence of PCV2 and PPV DNA by PCR, and for the presence of PCV2 antigen by immunohistochemistry (IHC). All the pigs had serum antibodies to PCV2 and PPV at the beginning of the trial. None of them developed clinical symptoms or pathological lesions typical of post-weaning multisystemic wasting syndrome (PMWS), a disease associated to PCV2 infection. However, IHC and/or PCR analyses showed that clinically silent PCV2 infection developed in five of the eight inoculated pigs, regardless of the administration of the vaccine. In particular, PCV2 DNA and/or antigen were detected in most of the tissues examined in the two pigs with the lowest titer of maternal PCV2 antibodies at the beginning of the trial. PPV DNA was not detected in any of the samples examined. The five pigs with PCR and/or IHC evidence of PCV2 infection had a mean weight gain during the experiment lower than that of the inoculated PCR-negative pigs considered together and that of the control pigs. In conclusion, it would appear that passive immunity against PCV2 can play a role in preventing the development of PMWS, but is not able to prevent the establishing of clinically silent PCV2 infections. The dissemination and persistence of the virus in the tissues may depend on the level of PCV2 antibodies at the time of inoculation.     

Retrospective study of porcine circovirus 2 infection in Japan: seven cases in 1989

Retrospectively, we demonstrated that seven pigs necropsied in 1989 had characteristic porcine circovirus 2 (PCV-2) lymphoid tissue lesions of severe lymphoid depletion, syncytial giant cell formation, and intracytoplasmic inclusion bodies in macrophages. Immunohistochemically, PCV-2 antigen was detected in these tissues and the distribution of positive staining corresponded to the distribution of inclusion bodies. Electron microscopy demonstrated viral particles compatible with porcine PCV-2. Therefore, the disease occurred in Japan as early as 1989.     

The emergence of a new strain of porcine circovirus-2 in Ontario and Quebec swine and its association with severe porcine circovirus associated disease — 2004–2006

In the late fall of 2004 more severe lesions of porcine circovirus-2 associated disease (PCVAD) than usual occurred during an outbreak of porcine circovirus-2 (PCV-2) infection in Ontario nursery and grower/finisher pigs. The lesions were of unprecedented severity and included diffuse bronchointerstitial pneumonia, granulomatous enteritis, vasculitis, interstitial nephritis, and new lesions of splenic infarction. Some affected herds had up to 50% mortality. The outbreak correlated with the sudden emergence of a variant PCV-2, with PCR restriction fragment length polymorphism (RFLP) type 321. Phylogenetic comparison of ORF2 sequences and full genome sequences showed the new variant to be different from the previously dominant RFLP type 422 viruses, and similar to viruses that had occurred in France and other European and Asian countries. A subsequent retrospective study showed a statistically significant increase in the frequency of histological lesions in lymph node, spleen, lung, small intestine, colon and kidney, for pigs spontaneously infected with RFLP type 321, compared with the older RFLP type 422 strain. Viral burden, based on IHC staining in lymph node, also showed a statistically significant increase in pigs infected with the newer variant RFLP type 321, compared with the older RFLP type 422 strain. This enhanced virulence in pigs infected with PCV-2 RFLP type 321 strain may be related to the genetic differences in this new strain of PCV-2. This virus is now the dominant strain of PCV-2 virus found in Ontario and Quebec swine.     

The prevalence of leptospirosis and its association with multifocal interstitial nephritis in swine at slaughter.

An abattoir survey was undertaken to determine the prevalence of leptospirosis and its association with lesions of multifocal interstitial nephritis (so-called "white spotted kidneys") in swine at slaughter. Both cross-sectional and case-control study designs were used. Of 197 kidneys from hogs randomly selected at slaughter, 11 (5.6%) had generalized grey-white foci typical of multifocal interstitial nephritis (MFIN). Antibody titers greater than or equal to 1:80 against Leptospira pomona were detected in nine (4.6%) hogs and against L. bratislava in 63 (32%) of these hogs. Leptospira pomona (kennewicki) was detected by immunofluorescence in 5/197 (2.5%) of randomly selected hogs. Leptospires identified as genotype kennewicki were isolated from six (9.8%) of 61 kidneys cultured. Leptospira bratislava was not detected by immunofluorescence or culture. There was a highly significant (p = 0.00) and strong association (odds ratio (OR) = 195) between high L. pomona titer (greater than or equal to 1:80) and the presence of leptospires in the kidneys, as detected by culture. There was also a significant (p = 0.046) and strong (OR = 8.10) association between multifocal interstitial nephritis and the presence of renal leptospires as detected by culture. The association between leptospiral titer and MFIN lesions in the prevalence survey group of animals was statistically significant (p = 0.031), but this association was not significant in the case-control study group (p = 0.071) The failure to identify L. bratislava despite serological evidence of infection suggests that some of these seropositive animals may have been transiently infected at an early age, that serological findings were falsely positive, or that immunofluorescence and isolation attempts failed to detect L. bratislava if they were indeed present in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)     

猪圆环病毒病研究进展

猪圆环病毒病是最近 1 0多年来才发现的一种新的猪病。研究表明 ,Ⅱ型猪圆环病毒 (PCV 2 )不仅是断奶仔猪多系统衰竭综合症 (PMWS)的病原 ,而且能够引起多种猪病。近年来 ,由PCV 2引起的疾病主要有PMWS、猪皮炎及肾病综合征、猪增生性坏死性肺炎等 ,另外 ,猪呼吸与繁殖障碍综合征、猪细小病毒、传染性先天性震颤等均与PCV 2感染有重要关联。随着规模化养殖业的不断发展 ,由PCV 2引起的疫病呈上升趋势 ,给全世界养猪业带来了巨大的经济损失。为了探讨有效控制本病的方法 ,特对该病的病原学、流行病学、致病机理、诊断及防制措施的研究情况进行了综述     

Renal pathology in specific-pathogen-free chickens inoculated with a waterfowl-origin type A influenza virus

Five-week-old specific-pathogen-free chickens inoculated intravenously with a waterfowl-origin type A influenza virus (A/mallard/Ohio/184/86) had swollen and mottled kidneys on days 3, 5, and 7 postinoculation (PI) and multiple raised nodules on days 5, 10, and 20 PI. Histologically, the kidneys had multifocal heterophilic tubulointerstitial nephritis with epithelial necrosis on day 3 PI, lymphoplasmacytic tubulointerstitial nephritis on day 5 PI, and fibrosing interstitial nephritis with cortical lobular collapse, atrophic tubules, glomerular aggregates, and interstitial lymphoid follicles and aggregates on days 7, 10, and 20 PI. Heterophilic intratubular medullary-cone nephritis was present in dead or moribund chickens on days 3 and 5 PI. Furthermore, the presence of mild multifocal heterophilic tubulointerstitial nephritis on day 20 PI suggests that a waterfowl-origin strain of type A influenza virus of low pathogenicity has the potential to produce acute and chronic active nephritis in the chicken and that the kidney is a potential site for influenza viral persistence. The acute, subacute, and chronic histopathologic renal lesions of this influenza virus in chickens are similar to lesions reported for some nephropathogenic infectious bronchitis viruses and avian nephritis picornavirus.     

山东潍坊地区PMWS临床病例的病理学研究

本研究对山东省潍坊地区8个猪场的断奶后仔猪多系统衰竭综合征(postweaning multisystemic wasting syndrome,PMWS)疑似病例在进行病原学诊断的基础上,作了系统的病理学研究,旨在为潍坊地区PMWS的诊断提供病理学诊断依据。结果表明潍坊地区PMWS病猪主要组织病理学变化表现为淋巴结和脾脏中缺少淋巴细胞,严重的单核、巨噬细胞和嗜酸性粒细胞浸润。在淋巴组织中出现类上皮样细胞以及合胞体性多核巨细胞形成的肉芽肿,巨噬细胞胞浆内有病毒包涵体。肺有间质性、支气管性肺炎;肝脏出现以肝细胞局灶性坏死、淋巴细胞浸润为特征的病变;肾脏有轻至重度的多灶性间质性肾炎;并表现不同程度的间质性心肌炎和非化脓性脑炎的病变。