The enterovirus comprises a large genus of viruses which produce a wide range of diseases. They are part of the larger family of Picornaviridae which also includes aphtoviruses, cardioviruses, and rhinoviruses. Classically, enterovirus includes the following diseases as outlined below. Transmission is usually by ingestion of fecally contaminated material. Incubation periods have ranged from 2 days to 2 weeks with the majority of infections occurring with 3-5 days following exposure. All of the viruses may cause aysmptomatic infection, a febrile illness with or without respiratory symptoms, aseptic meningitis, encephalitis, and paralysis. More specific illnesses have been associated with some groups or serotypes
VIRUS GROUP DISEASE COXSACKIE Coxsackie A 1-24 Herpangina
Coxsackie B 1-6 Exanthem
Generalized disease of the newborn
ECHOVIRUS Echovirus 1-34 Exanthem
Generalized disease of the newborn
Chronic meningoencephalitis in agammaglobulinemicsDiarrhea
POLIOVIRUS Poliovirus 1-3 ENTEROVIRUS SEROTYPES 68-72
EPIDEMIOLOGIC ASSOCIATIONS CHARACTERIZATION
Decline in immunity to polio among young adults.
Grotto I, Handsher R, Gdalevich M, Mimouni D, Huerta M, Green MS, Mendelson E, Shpilberg O.
Israel Defence Forces, Medical Corps, 02149, Military Post, Israel.
Vaccine 2001 Jul 20;19(30):4162-6 Abstract quote
A serologic survey was conducted on a population-based representative sample of 521 18-year-old soldiers recruited to the Israel Defence Forces in 1997. The prevalence of neutralizing antibodies and geometric mean titers (GMTs) against the three types of poliovirus (Mahoney, MEF and Saukett strains) were found to be 98.7% (GMT--169.95), 99.6% (GMT--297.14) and 96.4% (GMT - 59.48), respectively. These GMTs are markedly lower than those recorded 4 years after booster vaccination carried out during a 1988 polio outbreak, and suggest a decline in immunity against polio among young adults.
These findings support the policy of routine revaccination of children and adolescents in countries at risk of imported polioviruses and of revaccination of adults traveling to areas to which polio is endemic.
DISEASE ASSOCIATIONS CHARACTERIZATION CARDIAC
Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy.
Why HJ, Meany BT, Richardson PJ, Olsen EG, Bowles NE, Cunningham L, Freeke CA, Archard LC.
Cardiac Department, King's College Hospital, Denmark Hill, London, UK.
Circulation 1994 Jun;89(6):2582-9 Abstract quote
BACKGROUND: Enteroviral RNA sequences have been demonstrated in the myocardium of patients with myocarditis or dilated cardiomyopathy from presentation to end-stage disease. The prognosis of heart muscle disease has not previously been evaluated in relation to the detection of enterovirus in myocardial biopsy tissue.
METHODS AND RESULTS: We studied 123 consecutive patients with heart muscle disease prospectively. Multiple endomyocardial biopsy samples taken from all patients during diagnostic cardiac catheterization were classified histologically and were examined for enteroviral RNA by use of an enterovirus group-specific hybridization probe. Three enterovirus-negative patients with cardiac amyloidosis were excluded from subsequent analysis. Enteroviral RNA sequences were detectable in 41 (34%) of the remaining 120 patients (group A), while 79 (66%) had no virus detected (group B). The groups did not differ significantly in age, sex, symptomatic presentation, or hemodynamic characteristics; duration of symptoms was significantly shorter in group A (7.8 +/- 9.6 versus 14.9 +/- 19.0 months, P < .05). At follow-up (mean, 25 months; range, 11 to 50 months), patients from group A had an increased mortality compared with those in group B (25% versus 4%, respectively; P = .02). Mortality was also statistically greater in patients with symptomatic cardiac failure (P = .02), those with elevated left ventricular end-diastolic pressures (P = .03), and those in New York Heart Association functional classes III and IV (P = .05). Multivariate regression analysis, however, showed that only the presence of enterovirus RNA and symptomatic heart failure were of independent prognostic value.
CONCLUSIONS: These data demonstrate that the detection of enterovirus RNA in the myocardium of patients with heart muscle disease at the time of initial investigation is associated with an adverse prognosis and that the presence of enterovirus RNA is an independent predictor of clinical outcome.
Enteroviral genome in native hearts may influence outcome of patients who undergo cardiac transplantation.
Calabrese F, Valente M, Thiene G, Angelini A, Testolin L, Biasolo MA, Soteriou B, Livi U, Palu G.
Department of Pathology, University of Padua, Italy.
Diagn Mol Pathol 1999 Mar;8(1):39-46 Abstract quote
The Enterovirus may be the most common agent responsible for viral myocarditis and cardiomyopathy. Very little of the literature is available concerning the follow-up of patients who underwent transplantation with enteroviral positivity in native hearts.
In the present study, 45 explanted hearts from patients who underwent orthotopic heart transplant at University of Padova were studied by reverse transcriptase (RT)-polymerase chain reaction (PCR): 27 patients had dilated cardiomyopathy (DC), 12 had ischemic cardiopathy (IC), 2 had valvular disease (VD), 2 had arrhythmogenic right ventricular cardiomyopathy (ARVC), 1 had giant cell myocarditis (GCM), and 1 had lymphocytic myocarditis (LM). Two sets of PCR primers from the highly conserved region of Enterovirus and Rhinovirus were used. Samples of both ventricles and septum were analyzed in every patients. The RT-PCR and nucleotide sequencing of amplicons were also performed on all post-transplantation follow-up biopsies in patients with Enterovirus positivity in the native heart. The viral genome was detectable in only 1 of 27 patients with DC (3%) and in 1 patient with LM. Nucleotide sequence analysis of the amplified product showed differences in nucleotide sequence of PCR samples compared with the sequence of the coxsackievirus B3 used in the current study. The patient with Enterovirus-positive DC showed a higher index of severe rejection (>3A) in the first 6 months, compared with the other patients tested. The patient with Enterovirus-positive LM died of disease recurrence 2 months after transplantation.
The present study reveals a scarce presence of Enterovirus in the myocardium of patients with chronic myocardial disease. Because Enterovirus infection was predictive of a poor prognosis in these two patients, molecular studies are useful in excluding viral involvement in native hearts of transplanted patients.
Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: implications for cardiotropic viral infections.
Noutsias M, Fechner H, de Jonge H, Wang X, Dekkers D, Houtsmuller AB, Pauschinger M, Bergelson J, Warraich R, Yacoub M, Hetzer R, Lamers J, Schultheiss HP, Poller W.
Department of Cardiology and Pneumology, University Hospital Benjamin Franklin, Freie Universitat, Berlin, Germany.
Circulation 2001 Jul 17;104(3):275-80 Abstract quote
BACKGROUND: The coxsackievirus and adenovirus receptor (CAR) was identified as a common cellular receptor for both viruses, but its biological and pathogenic relevance is uncertain. Knowledge of CAR localization in the human cardiovascular system is limited but important with respect to CAR-dependent viral infections and gene transfer using CAR-dependent viral vectors.
METHODS AND RESULTS: Explanted failing hearts from 13 patients (8 with dilated cardiomyopathy [DCM] and 5 with other heart diseases [non-DCM]) and normal donor hearts (n=7) were investigated for the expression levels and subcellular localization of CAR and the adenovirus coreceptors alpha(v)beta(3) and alpha(v)beta(5) integrins. CAR immunoreactivity was very low in normal and non-DCM hearts, whereas strong CAR signals occurred at the intercalated discs and sarcolemma in 5 of the 8 DCM hearts (62.5%); these strong signals colocalized with both integrins. In all hearts, CAR was detectable in subendothelial layers of the vessel wall, but not on the luminal endothelial surface, and on interstitial cells. Human CAR (hCAR) expressed in rat cardiomyocytes was targeted to cell-cell contacts, which resembled CAR localization in DCM hearts and resulted in 15-fold increased adenovirus uptake.
CONCLUSIONS: Low hCAR abundance may render normal human myocardium resistant to CAR-dependent viruses, whereas re-expression of hCAR, such as that observed in DCM, may be a key determinant of cardiac susceptibility to viral infections. Asymmetric expression of hCAR in the vessel wall may be an important determinant of adenovirus tropism in humans. hCAR subcellular localization in human myocardium and hCAR targeting to cell-cell contacts in cardiomyocyte cultures suggest that hCAR may play a role in cell-cell contact formation.
MMWR Morb Mortal Wkly Rep 2001 Oct 12;50(40):874-5
Acute flaccid paralysis associated with circulating vaccine-derived poliovirus--Philippines, 2001.
MMWR Morb Mortal Wkly Rep 2001 Oct 12;50(40):874-5 Abstract quote
Three cases of acute flaccid paralysis (AFP) associated with circulating vaccine-derived poliovirus (cVDPV) isolates were reported in the Philippines during March 15-July 26, 2001. The first case-patient, a child aged 8 years from northern Mindanao island (500 miles south of Manila) who had received 3 doses of oral polio vaccine (OPV), had onset of paralysis on March 15. A second child, aged 3 years from Laguna province on Luzon island (60 miles south of Manila) who had received 3 OPV doses, presented with signs of meningitis but no paralysis on July 23. A third child, aged 14 months from Cavite province (25 miles from Manila and 45 miles north of Laguna province) who had received 2 OPV doses, had onset of paralysis on July 26. No patients had traveled outside of their province of residence since birth. Characterization of isolates from the three patients revealed type 1 polioviruses derived from Sabin vaccine strain type 1, with a 3% genetic sequence difference between Sabin 1 vaccine and vaccine-derived poliovirus (VDPV) isolates.
The three polioviruses are not identical but are closely related (>99% sequence homology); they also appear to share an identical recombination site with a nonpolio enterovirus in the noncapsid region of the genome.
Enterovirus in sudden unexpected deaths in infants.
Grangeot-Keros L, Broyer M, Briand E, Gut JP, Turkoglu S, Chretien P, Emilie D, Dussaix E, Lazizi Y, Dehan M.
Laboratories of Microbiology and Immunology, Hopital A. Beclere, Clamart, France.
Pediatr Infect Dis J 1996 Feb;15(2):123-8 Abstract quote
BACKGROUND: Conventional approaches to virus detection failed to provide convincing evidence of a viral etiology in sudden unexplained deaths in infants (SUDI). Many viruses may not have been detected by the routinely used methods; among them enteroviruses (EV) have seldom been found in SUDI.
METHODS: In this study EV were sought directly in stools, in pharyngeal and tracheal samples and in myocardial and lung tissues, by using a nested PCR; they were also sought indirectly by detecting IgM antibodies with a new capture immunoassay. Twenty-four SUDI cases were divided into two groups: Group I, certainly associated with; or Group II, not associated with clinical, biologic or histologic signs of viral infection.
RESULTS: EV were found in stools but their prevalence was not significantly different between Group I and Group II (20 and 22.2%, respectively). On the contrary EV were detected in respiratory tract and/or lung samples in 53.8% of infants of Group I and in none of Group II. Anti-EV IgM antibodies were detected in 55.5% of infants of Group I and in none of Group II.
CONCLUSIONS: These results indicate that EV infection may be specifically associated with the subgroup of SUDI with viral signs, raising the question of its role in this condition.
PATHOGENESIS CHARACTERIZATION COXSACKIE VIRUS
Secondary heterotypic versus homotypic infection by Coxsackie B group viruses: impact on early and late histopathological lesions and virus genome prominence.
Yu JZ, Wilson JE, Wood SM, Kandolf R, Klingel K, Yang D, McManus BM.
Department of Pathology and Laboratory Medicine, St Paul's Hospital-University of British Columbia, Vancouver, Canada.
Cardiovasc Pathol 1999 Mar-Apr;8(2):93-102 Abstract quote
The impact of prior exposure to a different or identical strain of Coxsackievirus B (CVB) on murine CVB myocarditis was studied using a susceptible murine host (A/J[H-2a]) and myocarditic CVB3 or avirulent CVB2 as primary or secondary infectants.
The effects of secondary heterotypic infection (CVB2 followed by CVB3) and homotypic infection (CVB3 followed by CVB3) 28 days after primary inoculation, versus CVB2 or CVB3 alone, on injury and viral genomic replication, both early (day 7) and late (days 28 and 56), were evaluated. After the primary infection by CVB2, trivial viral RNA was present in the heart and other organs, and a substantial positivity was observed with CVB3 infection. Seven days after secondary heterotypic (CVB2-CVB3) infection, the quantity of CVB genome in heart, pancreas, liver, and spleen was increased compared with the virus genome in the CVB3-CVB3 group and in the group with primary CVB3 infection alone. This phenomenon was seen in the heart and spleen up to day 28 postsecondary infection. Tissue inflammation and necrosis in heart and pancreas were prominent 7 days postsecondary infection with CVB2-CVB3 and correlated well with an increased quantity of CVB genome. Virus genome was present in heart and spleen 28 days after CVB3 infection alone. Serum CVB3 neutralization titer was increased to 1:128 in CVB2-CVB3 group at days 7 and 28 postsecondary infection, and serum completely neutralized cytopathological effects of CVB3 in the CVB3-CVB3 group at day 7 and 28 postsecondary infection.
Our results indicate that secondary heterotypic infection by CVB causes increased injury, inflammation, and CVB replication in target organs such as the heart and pancreas, as well as in immune compartments like the spleen. Compared with CVB3 alone, the intense inflammatory infiltriate in the CVB2-CVB3 group is as not due solely to postviral sensitization of the immune system, but rather to the inability of the host to eradicate the virus.
Coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology.
Mena I, Fischer C, Gebhard JR, Perry CM, Harkins S, Whitton JL.
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Virology 2000 Jun 5;271(2):276-88 Abstract quote
Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the destruction of exocrine tissue.
The physiological manifestations of pancreatic CVB infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of Langerhans. Here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. T-cell-mediated immunopathology has been invoked, along with direct virus-mediated cytopathicity, to explain certain aspects of CVB-induced pancreatic disease.
However, we show here that in the pancreas, the extent of inflammation and tissue destruction appears unaltered in the absence of the cytolytic protein perforin; these findings exclude any requirement for perforin-mediated lysis by natural killer cells or cytotoxic T cells in CVB3-induced pancreatic damage. Furthermore, perforin-mediated cytotoxic T-cell activity does not contribute to the control of CVB infection in this organ. In addition, we demonstrate that the recently identified coxsackie-adenovirus receptor is expressed at high levels in acinar cells but is barely detectable in islets, which is consistent with its being a major determinant of virus tropism and, therefore, of disease. However, further studies using various cell lines of pancreatic origin reveal secondary determinants of virus tropism.
Mechanisms of coxsackievirus-induced damage to human pancreatic beta-cells.
Roivainen M, Rasilainen S, Ylipaasto P, Nissinen R, Ustinov J, Bouwens L, Eizirik DL, Hovi T, Otonkoski T.
Enterovirus Laboratory, National Public Health Institute, Helsinki, Finland.
J Clin Endocrinol Metab 2000 Jan;85(1):432-40 Abstract quote
Enteroviruses may be involved in the pathogenesis of insulin-dependent diabetes mellitus, either through direct beta-cell infection or as triggers of autoimmunity.
In the present study we investigated the patterns of infection in adult human islet cell preparations (consisting of 56+/-14% beta-cells) by several coxsackieviruses. The cells were infected with prototype strains of coxsackievirus B (CBV) 3, 4, and 5 as well as coxsackievirus A9 (CAV-9). The previously characterized diabetogenic strain of coxsackievirus B4 (CBV-4-E2) was used as a reference. All viruses replicated well in beta-cells, but only CBVs caused cell death. One week after infection, the insulin response of the beta-cells to glucose or glucose plus theophylline was most severely impaired by CBV-3 and CBV-5 infections. CBV-4 also caused significant functional impairment, whereas CAV-9-infected cells responded like uninfected controls. After 2 days of infection, about 40% of CBV-5-infected cells had undergone morphological changes characteristic of pyknosis, i.e. highly distorted nuclei with condensed but intact chromatin. Both mitochondria and plasma membrane were intact in these cells. DNA fragmentation was found in 5.9+/-1.1% of CBV-5-infected beta-cell nuclei (2.1+/-0.3% in controls; P<0.01). CAV-9 infection did not induce DNA fragmentation. One week after infection the majority of infected cells showed characteristics of secondary necrosis. Medium nitrite and inducible nitric oxide synthase messenger ribonucleic acid levels were not significantly up-regulated by CBV infection. These results suggest that several enteroviruses may infect human beta-cells. The infection may result in functional impairment or death of the beta-cell or may have no apparent immediate adverse effects, as shown here for CAV-9.
Coxsackie B viruses cause functional impairment and beta-cell death characterized by nuclear pyknosis. Apoptosis appears to play a minor role during a productive CBV infection in beta-cells.
CHARACTERIZATION RADIOLOGIC LABORATORY MARKERS
Rapid Detection of Enterovirus RNA in Cerebrospinal Fluid Specimens with a Novel Single-Tube Real-Time Reverse Transcription-PCR Assay.
Verstrepen WA, Kuhn S, Kockx MM, Van De Vyvere ME, Mertens AH.
Center for Molecular Diagnostics, OCMW Hospitals, Antwerp, Belgium.
J Clin Microbiol 2001 Nov;39(11):4093-6 Abstract quote
A single-tube real-time reverse transcription-PCR (RT-PCR) assay for enterovirus detection in cerebrospinal fluid (CSF) was developed based on a fluorogenic probe and primers directed to highly conserved sequences in the 5' untranslated region of the enterovirus genome.
Quantitative detection of enterovirus genome was demonstrated in a linear range spanning at least 5 logs. Endpoint titration experiments revealed that the in-tube detection limit of the assay was 11.8 enterovirus genome equivalents (95% detection rate) corresponding in our current extraction protocol to 592 enterovirus genome equivalents per ml of CSF. Twenty CSF specimens not suspected of viral meningitis were all found to be negative, and no cross-reactivity with herpes simplex virus type 1 and type 2, varicella-zoster virus, rhinovirus type 53, and influenza viruses A and B was observed. Nineteen CSF specimens from 70 patients suspected of viral meningitis were determined to be positive by PCR (27.1%), whereas only 17 were found to be positive by viral culture (24.3%). The sensitivity of the assay was 100% and the specificity was 96.2% compared to viral culture. Data from the real-time RT-PCR assay were available within 4 h.
Our data suggest that the novel real-time RT-PCR assay may offer a reliable but significantly faster alternative to viral culture. Owing to the elimination of postamplification detection steps, its conduct required considerably less hands-on time and was associated with a substantially reduced carryover risk compared to previously described PCR-based enterovirus detection assays.
Comparison of a multiplex reverse transcription-pcr-enzyme hybridization assay with conventional viral culture and immunofluorescence techniques for the detection of seven viral respiratory pathogens.
Liolios L, Jenney A, Spelman D, Kotsimbos T, Catton M, Wesselingh S.
Infectious Diseases Unit, Alfred Hospital, Prahran 3181, Victoria, Australia.
J Clin Microbiol 2001 Aug;39(8):2779-83 Abstract quote
A multiplex reverse transcription-PCR-enzyme hybridization assay (RT-PCR-EHA; Hexaplex; Prodesse Inc., Waukesha, Wis.) was used for the simultaneous detection of human parainfluenza virus types 1, 2, and 3, influenza virus types A and B, and respiratory syncytial virus types A and B.
One hundred forty-three respiratory specimens from 126 patients were analyzed by RT-PCR-EHA, and the results were compared to those obtained by conventional viral culture and immunofluorescence (IF) methods. RT-PCR-EHA proved to be positive for 17 of 143 (11.9%) specimens, whereas 8 of 143 (5.6%) samples were positive by viral culture and/or IF. Eight samples were positive by both RT-PCR-EHA and conventional methods, while nine samples were RT-PCR-EHA positive and viral culture and IF negative. Eight of the nine samples with discordant results were then independently tested by a different multiplex RT-PCR assay for influenza virus types A and B, and all eight proved to be positive.
In comparison to viral culture and IF methods, RT-PCR-EHA gave a sensitivity and a specificity of 100 and 93%, respectively. Since RT-PCR-EHA was able to detect more positive samples, which would otherwise have been missed by routine methods, we suggest that this multiplex RT-PCR-EHA provides a highly sensitive and specific means of diagnostic detection of major respiratory viruses.
Prospective analysis of 61 cases of enteroviral meningitis: interest of systematic genome detection in cerebrospinal fluid irrespective of cytologic examination results.
Henquell C, Chambon M, Bailly JL, Alcaraz S, De Champs C, Archimbaud C, Labbe A, Charbonne F, Peigue-Lafeuille H.
Laboratoire de Virologie, Faculte de Medecine, 28, Place Henri-Dunant, 63001 Clermont-Ferrand Cedex, France.
J Clin Virol 2001 Apr;21(1):29-35 Abstract quote
BACKGROUND: Enteroviruses are the most commonly identified cause of viral meningitis. Detection of the enterovirus genome in cerebrospinal fluid (CSF) using reverse-transcription polymerase chain reaction (PCR) has proved to be useful in diagnosis and is more rapid and sensitive than viral cultures. In routine practice, cytologic examination results of CSF are obtained swiftly and PCR indication is performed as a second step.
OBJECTIVES: The aim of this study was to determine, by analysis of complete data from CSF results for 61 cases of proven enteroviral meningitis, whether cytologic CSF findings can be used to establish viral etiology and to indicate if PCR assay should be performed.
STUDY DESIGN: From a prospective study of children admitted during 1997 for suspected enterovirus meningitis in which PCR and viral cultures of CSF were systematically performed, we selected 61 patients with proven enterovirus meningitis. We compared global white cell count (WCC), relative percentage of lymphocytes/neutrophils, PCR and culture for enterovirus, patient age, and clinical data.
RESULTS: 92% of patients (56/61) had positive PCR in CSF and in 48% (29/61) enterovirus was isolated in CSF. Nine patients (14.75%) had WCC<10/mm(3); eight of them had positive PCR and two had positive culture. There were comparable numbers of CSF with a predominance of lymphocytes (n=25) and CSF with a predominance of neutrophils (n=22), and of positive PCR and positive cultures of CSF in the two groups. Results were not influenced by the age of the patients.
CONCLUSION: Irrespective of other CSF parameters, it seems difficult to dispense with PCR assay for enterovirus genome detection. It should be introduced as a true rapid routine test. Early reporting of a positive PCR result could result in a considerable saving in health resources.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS TREATMENT
Treatment of neonatal infection caused by coxsackievirus B3.
Kimura H, Minakami H, Harigaya A, Takeuchi H, Tachibana A, Otsuki K.
Gunma Prefectural Institute of Public Health and Environmental Sciences, Maebashi, Japan.
J Perinatol 1999 Jul-Aug;19(5):388-90 Abstract quote
Four male infants with early neonatal infection caused by coxsackievirus B3 (presumed in one case) exhibited severe thrombocytopenia and liver dysfunction at presentation.
The three infants who were administered human normal immunoglobulin within 3 days of disease onset survived, while the fourth infant, who received the preparation 6 days after disease onset, died.
Treatment of potentially life-threatening enterovirus infections with pleconaril.
Rotbart HA, Webster AD
Pleconaril Treatment Registry Group. Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Clin Infect Dis 2001 Jan 15;32(2):228-35 Abstract quote
Enteroviruses usually cause self-limited disease that, although associated with high morbidity, is rarely fatal. In certain patient populations, however, the enteroviruses may cause potentially life-threatening infections. Pleconaril is a novel compound that integrates into the capsid of picornaviruses, including enteroviruses and rhinoviruses, preventing the virus from attaching to cellular receptors and uncoating to release RNA into the cell.
Pleconaril was used on a compassionate-release basis to treat patients with potentially life-threatening enterovirus infections, and for 38 of these patients sufficient follow-up data were available for determining responses to therapy. Response was evaluated in 4 categories: clinical, virological, laboratory, and radiological. Most patients (28 [78%] of 36), including 12 of 16 with chronic enterovirus meningoencephalitis, were judged to have a clinical response temporally associated with pleconaril therapy.
Similarly, nearly all patients whose virological responses (12 [92%] of 13), laboratory responses (14 [88%] of 16), and radiological responses (3 [60%] of 5) could be evaluated were judged to have responded favorably to a course of pleconaril treatment. Adverse effects were minimal and the drug was generally well-tolerated.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
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