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PubMed2000

Diagnosis of nipah virus encephalitis by electron microscopy of cerebrospinal fluid.

BACKGROUND: between 1998 and 1999, an outbreak of potentially fatal viral encephalitis erupted among pig farm workers in West Malaysia, and later spread to Singapore where abattoir workers were afflicted. Although Japanese encephalitis virus was initially suspected, the predominant aetiologic agent was subsequently confirmed to be Nipah virus, a novel paramyxovirus related to but distinct from Hendra virus. OBJECTIVE: to describe a case of Nipah virus encephalitis in a pig farm worker from Malaysia. STUDY DESIGN: the clinical, laboratory and radiological findings of this patient were scrutinized. Special emphasis was placed on the electron microscopic analysis of the cerebrospinal fluid (CSF) specimen from this patient. RESULTS: the neurological deficits indicative of cerebellar involvement were supported by the magnetic resonance imaging that showed prominent cerebellar and brainstem lesions. CSF examination provided further evidence of viral encephalitis. Complement fixation and/or RT-PCR assays were negative for Japanese encephalitis, herpes simplex, measles and mumps viruses. ELISA for detecting IgM and IgG antibodies against Hendra viral antigens were equivocal for the CSF specimen, and tested initially negative for the first serum sample but subsequently positive for the repeat serum sample. Transmission electron microscopy of negatively-stained preparations of CSF revealed enveloped virus-like structures fringed with surface projections as well as nucleocapsids with distinctive helical and herringbone patterns, features consistent with those of other paramyxoviruses, including Hendra virus. CONCLUSION: this case report reiterates the relevant and feasible role of diagnostic electron microscopy for identifying and/or classifying novel or emerging viral pathogens for which sufficiently specific and sensitive tests are lacking.

Antibodies, Viral↗
PubMed2006

Trends in encephalitis-associated deaths in the United States.

The United States national mortality statistics and HIV/AIDS surveillance data were analysed to determine trends in encephalitis-associated deaths and to assess the impact of HIV infection on those deaths during 1979-1998, a period when ICD-9 codes were used for coding deaths in the United States. A total of 25125 encephalitis deaths were reported; 4779 of them (19%) had concurrent HIV infection. Overall encephalitis death rates remained stable, but they increased for groups where HIV infection was common and declined or remained unchanged for others. For persons without HIV infection, the rates declined in all demographic groups. Encephalitis deaths in HIV-infected persons followed general trends for HIV deaths in the United States. The rates in the HIV-infected population were several hundred- to thousand-fold higher than in the HIV-uninfected population. HIV infection was largely responsible for the lack of overall decline in the considerable mortality associated with encephalitis in the United States during 1979-1998.

Adolescent↗
PubMed1999

Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis.

Apoptosis of neurones, macrophages, and microglia occurs in the brains of paediatric patients with human immunodeficiency virus (HIV) type 1 encephalitis, which is often associated with pre-mortem neurological disease (progressive encephalopathy). We have previously reported that TUNEL-positive neurones in brain tissue from paediatric patients with HIV type 1 encephalitis and progressive encephalopathy are strikingly devoid of the pro-apoptotic gene product Bax, in marked contrast to brain-resident macrophages and microglia. Using immunocytochemical methods, the present study demonstrate that neurones in patients with HIV type 1 encephalitis and progressive encephalopathy, as well as macrophages and microglia, but not astrocytes, overexpress caspase-3, a pro-apoptotic enzyme that is proteolytically activated downstream of Bax-Bcl-2 dysregulation. Co-localization of neuronal cytoplasmic caspase-3 and nuclear TUNEL staining, a marker for fragmented DNA, was also infrequently observed in brain tissue from patients with HIV type 1 encephalitis and progressive encephalopathy. These findings suggest that vulnerable neurones in brain tissue from patients with HIV virus type 1 encephalitis and progressive encephalopathy undergo apoptosis by a mechanism that involves upregulation of caspase-3 in a pathway that is independent of Bax-Bcl-2 dysregulation. Furthermore, caspase-3 upregulation in apoptotic neurones likely occurs prior to DNA fragmentation.

AIDS Dementia Complex↗
PubMed1995

[Necrotizing herpes simplex encephalitis as the cause of a progressive dementia syndrome].

HISTORY AND FINDINGS: A 65-year-old woman was twice hospitalized because of disorientation and insomnia with depression. In the course of antidepressive treatment the symptoms regressed each time so that the diagnosis was made of pseudo-dementia during depression. About a year after the first admission the symptoms recurred, despite continued antidepressive treatment. Clinical criteria now suggested Alzheimer-type dementia as the diagnosis. COURSE AND TREATMENT: The symptoms of dementia increased markedly and generalized seizures requiring anticonvulsive drugs occurred after 4 months. Although IgG antibodies against Herpes simplex virus (HSV) were demonstrated in cerebrospinal fluid (CSF), no antiviral treatment was instituted because HSV encephalitis appeared unlikely at this stage. But the patient's mental and physical state further deteriorated in subsequent months. During an attack of pneumonia the patients became somnolent and went into status epilepticus. Repeat virological examination of CSF now revealed IgG and IgM antibodies against HSV, confirming encephalitis. Her condition markedly improved over 12 days on aciclovir, 750 mg 3 times daily intravenously. 6 weeks later the pneumonia recurred, as did the encephalitis, with apnoeic phases and massive left heart failure. The patient died a few days later. Immunohistochemical tests of brain tissue were positive for HSV type II. CONCLUSIONS: This case report demonstrates that an investigation on dementia must include a complete liquor analysis. If HSV encephalitis is suspected, an antiviral therapy must be administered immediately. Even in adults who seem to have normal immunity HSV type II can cause HSV encephalitis.

Aged↗
PubMed2001

La Crosse encephalitis in children.

BACKGROUND: La Crosse encephalitis is a mosquito-borne disease that can be mistaken for herpes simplex encephalitis. It has been reported in 28 states but may be underrecognized. METHODS: We investigated the manifestations and clinical course of La Crosse encephalitis in 127 patients hospitalized from 1987 through 1996. The diagnosis was established by serologic testing for IgM and IgG antibodies to La Crosse virus. Data were collected by chart review. RESULTS: Most of the patients were school-aged children (mean [+/-SD] age, 7.8+/-3.5 years; range, 0.5 to 15.0). Symptoms included headache, fever, and vomiting (each in 70 percent or more of the patients), seizures (in 46 percent), and disorientation (in 42 percent). Thirteen percent had aseptic meningitis. Hyponatremia developed in 21 percent, and there were signs of increased intracranial pressure in 13 percent. Six patients, including three with cerebral herniation, underwent intracranial-pressure monitoring. The 13 patients (11 percent) whose condition deteriorated in the hospital had decreases in serum sodium levels (P=0.007), and increases in body temperature (P=0.003) at the time of deterioration. At admission, these patients more often had a history of vomiting (P=0.047) and a score of 12 or lower on the Glasgow Coma Scale (P=0.02) than the others; a trend toward a greater prevalence of seizures at admission was also evident in this group (P=0.07). All the patients survived, but 15 of them (12 percent) had neurologic deficits at discharge. Follow-up assessments, performed in 28 children, suggested an increase in cognitive and behavioral deficits 10 to 18 months after the episode of encephalitis. CONCLUSIONS: La Crosse virus infection should be considered in children who present with aseptic meningitis or encephalitis. Hyponatremia and increasing body temperature may be related to clinical deterioration.

Adolescent↗
PubMed2004

In vivo monitoring of acute flavivirus (Modoc) encephalitis with regional and whole-brain quantitative diffusion magnetic resonance imaging.

In vivo imaging of structural changes in the brain of patients with encephalitis has become an important aid in diagnostic and therapeutic procedures. Diffusion-weighted magnetic resonance imaging (DWI) was employed to quantitate regional and whole-brain diffusion-weighted MRI changes in a hamster model for acute flavivirus encephalitis. The regional apparent diffusion coefficient (ADC) was determined in hyperintense regions seen on T2-weighted images (i.e., the thalamic area and the temporal lobe), but anatomical variation and structural heterogeneity of encephalitic lesions severely impeded the placement of regions of interest (ROI). Therefore, quantitative whole-brain diffusion-weighted imaging was carried out and revealed a significantly reduced ADC (P = .02) in the brain of hamsters with acute encephalitis (n = 7) as compared to that of healthy, uninfected controls (n = 3). Furthermore, the ADC histogram demonstrated a reduced peak height and center of gravity during the acute encephalitis. Our findings could further support the use of diffusion-weighted imaging for in vivo monitoring of acute flavivirus encephalitis and for the study of therapeutic approaches.

Animals↗
PubMed1992

Viral neuroinvasion and encephalitis induced by lipopolysaccharide and its mediators.

The present study was designed to test the effect of bacterial endotoxin on penetration of viruses into the central nervous system (CNS). As a model we used two neurovirulent viruses that lack neuroinvasive capacity: West Nile virus-25 (WN-25) and neuroadapted Sindbis virus (SVN). Administration of lipopolysaccharide (LPS, 100 micrograms/mouse) to CD-1 mice, followed by WN-25 inoculation resulted in 83% encephalitis and death, compared with less than 5% in controls. The results in SVN-inoculated CD-1 mice were quite similar. LPS-treated mice suffered 62% mortality compared with 6% in the nontreated group. No changes in viral neuroinvasiveness were demonstrated in viruses isolated from brains of encephalitic mice, suggesting that neuroinvasion is not due to a selection process for an invasive variant, but to direct penetration of the viruses through the blood-brain barrier (BBB). LPS did not induce WN-25 encephalitis in LPS-insensitive C3H/HeJ mice, compared with 100% neuroinvasion in C3H/HeB mice. Induction of neuroinvasion could be transferred to C3H/HeJ mice by transfusion with serum obtained from LPS-treated, LPS-responsive mice. Passive immunization of CD-1 mice with anti-mTNF antibodies before LPS administration did not prevent LPS-induced WN-25 encephalitis. Furthermore, neutralization of tumor necrosis factor activity in the serum of LPS-treated mice did not abolish its activity, and transfusion-associated encephalitis was observed after the administration of the neutralized serum with WN-25. We suggest that LPS can contribute to virus penetration from the blood into the CNS, a process which turns a mild viral infection into a severe lethal encephalitis. This effect is mediated by soluble factors, and is probably achieved by injury to cerebral microvascular endothelium and modulation of BBB permeability.

Animals↗
PubMed2001

Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow transplant recipients.

To determine whether receipt of an investigational anti-CD3 monoclonal antibody (BC3) increased the risk of human herpesvirus 6 (HHV-6) reactivation and development of encephalitis in bone marrow transplant (BMT) recipients, persons who had and had not received BC3 were compared. Odds of HHV-6 reactivation were higher among BC3 recipients than among control patients (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In addition, BC3 recipients were more likely than control patients to develop encephalitis (risk ratio [RR], 3.5; 95% CI, 1.3-9.5), and this association followed a BC3 dose-dependent relationship (P=.03, by Mantel-Haenszel chi(2) test). In a multivariable model, HHV-6 reactivation and receipt of BC3 were associated with increased risk of encephalitis (RR, 5.4; 95% CI, 1.9-15.3, and RR, 3.3; 95% CI, 1.2-9.1, respectively). In conclusion, both HHV-6 reactivation and receipt of BC3 for prophylaxis of acute graft-versus-host disease independently increased the risk of encephalitis in allogeneic BMT recipients. Prospective studies to better define the relationship between HHV-6 reactivation and encephalitis in allogeneic BMT recipients are warranted.

Adult↗
PubMed2006

Clinical features in children hospitalized during the 2005 epidemic of Japanese encephalitis in Uttar Pradesh, India.

BACKGROUND: Japanese encephalitis is a disease that affects the rural poor in Asia. In August-September 2005, a severe epidemic of Japanese encephalitis occurred in Uttar Pradesh, one of India's poorest states. METHODS: Children admitted to the King George Medical University hospital (Lucknow, Uttar Pradesh, India) with acute febrile encephalopathy (defined as fever plus encephalopathy of <or=2 weeks' duration) from July to October 2005 underwent ELISA for Japanese encephalitis virus immunoglobulin M in cerebrospinal fluid or serum on hospital admission. Clinicolaboratory features of patients with positive test results were recorded.Results. Of the 223 children tested, 77 had positive results for Japanese encephalitis immunoglobulin M. Patients were from 18 districts of Uttar Pradesh. All but 1 were from rural areas, and none were <2 years of age. The prodromal period was very short (mean+/-standard deviation, 2.61+/-2.23 days). Convulsions were present in 76 patients (98.7%). The mean (+/- standard deviation) Glasgow Coma Scale score was 7.4+/-2.7. Generalized hypertonia was found in 39 patients (50.6%), and focal deficits were found in 35 patients (45.4%), including 19 cases of monoparesis and 16 cases of hemiparesis. Gastric hemorrhage was found in 42 patients (54.5%). Extrapyramidal features were found in 24 (31.1%), a hyperepneic breathing pattern was found in 20 (26%), and thrombocytopenia was found in 5 (15.6%) of 32 patients. The mean cerebrospinal fluid cell count was 48.3 cells/mm(3). The serum bilirubin level was normal in all patients, but the aspartate aminotransferase level was elevated in all 21 patients (100%) tested and the alanine aminotranferase level was elevated in 25 (47.2%) of 53 patients. In-hospital mortality was 34%. CONCLUSIONS: Clinical features of Japanese encephalitis were severe. Derangements in liver function and thrombocytopenia were found in a significant proportion of patients. These findings were not highlighted during earlier epidemics of the illness and could suggest a possible mutation of the virus towards other flaviviruses.

Child↗
PubMed1997

Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples.

Detection of DNA from herpes simplex virus in cerebrospinal fluid (CSF) samples by polymerase chain reaction (PCR) analysis has been shown to be more sensitive and specific for the diagnosis of herpes simplex encephalitis than isolation of herpes simplex virus from biopsy specimens of brain tissue. Because of the invasiveness of brain biopsy, it has been suggested that PCR analysis of CSF may reveal a wider spectrum of the disease than has been previously recognized by brain biopsy studies. In this study, PCR assay of CSF samples obtained from 29, 12, and 8 patients with focal, mild, and diffuse encephalitis, respectively, was performed. PCR assay was positive for 15 (51.7%) of 29 patients with focal encephalitis and three (25%) of 12 patients with mild encephalitis. The correlation between temporal abnormalities shown by electroencephalography, computed tomography of the brain, or cranial magnetic resonance imaging and a positive PCR assay was high. PCR analysis has revealed that atypical and less severe forms of encephalitis are caused by herpes simplex virus.

Adolescent↗
PubMed1998

The level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid as a marker of HIV encephalitis.

We prospectively evaluated the level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid (CSF) as a marker of HIV encephalitis. Fifty-two HIV-1-infected patients (41 males and 11 females; mean age, 39 years) were tested for the presence of HIV-1 RNA in plasma and CSF. Samples of CSF were obtained by lumbar puncture to evaluate cognitive deficits, seizures, or fever among these patients. HIV encephalitis was diagnosed in 11 patients (21%), other CNS diseases were diagnosed in 12 (23%), and fever without CNS disease was diagnosed in 29 (56%). HIV-1 RNA was detectable in 92% of the plasma specimens and 75% of the CSF specimens. No significant difference was observed in CSF levels of HIV-1 RNA between patients with or without HIV encephalitis. CSF levels of HIV-1 RNA correlated with plasma levels of HIV-1 RNA (Spearman's rank correlation, +0.31; P = .02) and CSF white blood cell counts (Spearman's rank correlation, +0.4; P < .01). The absence of any significant difference between patients with or without HIV encephalitis suggests that the CSF HIV-1 RNA level is not a good marker for the diagnosis of HIV encephalitis.

AIDS Dementia Complex↗
PubMed1977

Encephalitis in ferrets caused by a nonproductive strain of measles virus (D.R.) isolated from patient with subacute sclerosing panencephalitis.

A nonproductive, syncytiogenic strain (D.R.) of measles virus, isolated from a patient with subacute sclerosing panencephalitis (SSPE), was inoculated intracerebrally into ferrets in an attempt to induce subacute encephalitis. Inoculation of freeze-thawed syncytia before immunization was the least effective procedure, and inoculation of live syncytia after immunization with measles virus vaccine was the most effective procedure, for induction of subacute or persistent subclinical encephalitis in the animals. After the latter procedure three of five ferrets developed subacute or subclinical encephalitis, whereas ferrets inoculated with live syncytia without prior immunization consistently contracted acute fatal encephalitis in one to two weeks. The subacute encephalitis in ferrets was characterized by high titers of antibody to measles virus in serum. At the time of sacrifice 1.25, 4.5, or 8.0 months after inoculation, brains of the ferrets showed histologic lesions similar to those characteristic of SSPE, and nonproductive syncytiogenic measles virus was recovered from the brains of two of the animals. All three ferrets had greatly increased concentrations of gamma-globulin in their brains and high levels of neutralizing and hemagglutination-inhibiting antibodies to measles virus. Only one of these animals developed clinical signs 1.25 months after inoculation.

Animals↗
PubMed1996

Selective elevation of monocyte chemotactic protein-1 in the cerebrospinal fluid of AIDS patients with cytomegalovirus encephalitis.

The CC chemokine monocyte chemotactic protein-1 (MCP-1) was markedly elevated in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-infected patients with cytomegalovirus (CMV) encephalitis. The MCP-1 CSF levels in CMV encephalitis were markedly higher than those in the CSF of HIV-infected patients with or without unrelated neurologic diseases, including progressive multifocal leukoencephalopathy, cryptococcal meningitis, toxoplasmic encephalitis, and primary lymphoma. Interleukin-8, RANTES, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta were not substantially increased in the CSF of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurologic disorders associated with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1993

Etiology of acute encephalitis in childhood in Slovenia.

The etiology of acute encephalitis was evaluated in a retrospective study of 170 children (98 boys and 72 girls) ages 1 month to 15 years, who were hospitalized during a 13-year period from 1979 to 1991. The etiology was confirmed or considered very probable in 68% of cases. The identified etiologic agents included Central European tick-borne encephalitis virus (28.8%), varicella-zoster virus (17.0%), herpes simplex (10.0%), rubella (2.9%), mumps (2.3%), measles virus, Chlamydia psittaci (1.1%) and some other agents found in individual cases. The etiology remained unknown in 54 children (31.7%). Forty-two patients had encephalitis with focal neurologic signs. The most common confirmed or presumptive infective agent in those cases was herpes simplex virus (40.4%), followed by rubella (7.1%), Central European tick-borne encephalitis virus (4.7%) and some other agents identified in individual cases. The etiology remained unknown in 15 (36%) children with focal encephalitis.

Acute Disease↗
PubMed1996

Acute manifestations and neurologic sequelae of Epstein-Barr virus encephalitis in children.

BACKGROUND: Complications of Epstein-Barr virus (EBV) infection are diverse and include a number of neurologic manifestations such as meningitis, meningoencephalitis, cerebellitis, cranial neuritis and others. In general encephalitis caused by EBV in pediatric patients has been considered a self-limited illness with few or no sequelae. METHODS: Charts were reviewed from all patients < 18 years of age admitted to or discharged from the State University of New York Health Science Center at Syracuse between 1982 and 1992 with a diagnosis of encephalitis or meningo-encephalitis. Eleven cases of EBV encephalitis diagnosed during a 10-year period were reviewed to characterize the clinical and laboratory findings in the acute setting and the extent of neurologic sequelae on follow-up. RESULTS: Acute neurologic manifestations were diverse and included combative behavior (55%), seizures (36%), headache (36%) and evidence of focal involvement (27%). Classic findings of infectious mononucleosis were noted infrequently; 18% each had pharyngitis, adenopathy, positive heterophile antibody tests or atypical lymphocytosis. Two patients (18%) had abnormal neuroimaging studies, one in the acute stage and the other at the time of follow-up. Seven patients (64%) had abnormal electroencephalograms (EEGs) in the acute setting; of these three had persistent abnormalities on follow-up. Forty percent developed persistent neurologic abnormalities including global impairment, perseverative autistic-like behavior and persistent left upper extremity paresis. CONCLUSIONS: Classic signs, symptoms and laboratory findings in infectious mononucleosis may be absent in Epstein-Barr virus encephalitis. Neurologic sequelae occur in a substantial number of patients.

Acute Disease↗
PubMed2004

Successful treatment of life-threatening human herpesvirus-6 encephalitis with donor lymphocyte infusion in a patient who had undergone human leukocyte antigen-haploidentical nonmyeloablative stem cell transplantation.

BACKGROUND: Encephalitis as the result of human herpesvirus (HHV)-6 is usually fatal when it is resistant to antiviral drugs. METHODS: We describe a patient who developed HHV-6 encephalitis after human leukocyte antigen-haploidentical transplantation using a reduced intensity regimen. RESULTS: The patient developed severe disorientation, amnesia, and tremors on day 28. Magnetic resonance imaging of the brain revealed limbic encephalitis, and the cerebrospinal fluid sample was positive for only HHV-6 in polymerase chain reaction analysis. Neither ganciclovir nor foscarnet was effective. The patient recovered from the critical condition of HHV-6 encephalitis after donor lymphocyte infusion (DLI). Almost all of his symptoms resolved, polymerase chain reaction tests for HHV-6 in the cerebrospinal fluid were negative, and magnetic resonance imaging findings were normal. CONCLUSIONS: This is the first report of DLI as a treatment for HHV-6 encephalitis and the first report of DLI from an human leukocyte antigen-haploidentical donor as a treatment for life-threatening viral infection.

Adult↗
PubMed2006

The evolving epidemiology of viral encephalitis.

PURPOSE OF REVIEW: The introduction of West Nile virus to North America illustrates the potential emergence of novel encephalitic agents in unexpected settings. There has been continued recognition of emerging neurotropic viruses in both the developed and developing world and novel modes of transmission of these agents. This review describes recent developments in the epidemiology of West Nile virus and several other emerging viral encephalitides in the developed and developing world and the emergence of novel mechanisms of transmitting viral encephalitis. RECENT FINDINGS: West Nile virus has continued to have a large public health impact in North America. Improvements in blood donor screening have decreased transfusion-associated transmission of the virus. Monkeypox, with associated encephalitis, occurred in the US. Chandipura virus, an infrequently recognized rhabdovirus, was attributed to large outbreaks of viral encephalitis; however, compelling evidence suggests that the relationship of illness and the virus are questionable. Recent cases of transfusion-associated and transplant-associated viral encephalitis, including West Nile virus, rabies virus, and lymphocytic choriomeningitis virus, were described. SUMMARY: Continued West Nile virus activity in North America reinforces the fact that viruses can emerge and thrive in new environments and unexpected settings and suggests the need for continued surveillance. Transfusion-associated and transplant-associated viral encephalitis may be an underrecognized risk of these procedures.

Animals↗
PubMed2006

Rapid detection and quantification of Japanese encephalitis virus by real-time reverse transcription loop-mediated isothermal amplification.

We established a rapid, quantitative real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay targeting the envelope gene of Japanese encephalitis virus. The RT-LAMP enabled us to detect the target product within 1 hr by only reacting reverse transcriptase and Bst DNA polymerase in a single tube at an isothermal temperature. The detection sensitivity of the RT-LAMP for Japanese encephalitis virus was 1 PFU, similar to that of conventional reverse transcription-polymerase chain reaction (RT-PCR). Flaviviruses of the Japanese encephalitis virus group, such as Dengue virus and West Nile virus, could not be detected. This confirmed the specificity of the RT-LAMP assay for Japanese encephalitis virus. A standard curve was constructed by plotting viral titer against the time for virus detection by the RT-LAMP, validating the quantitative accuracy of the assay. In addition, the amount of virus estimated by RT-LAMP was strongly correlated (r = 0.902) with that determined by plaque assay, a conventional method for virus quantification. These results indicate that the RT-LAMP assay established in this study is specific for Japanese encephalitis virus, and allows more rapid detection and quantification of the virus.

Animals↗