Showing papers in "Journal of Medical Virology in 1993"
TL;DR: Results with PCR as a rapid and sensitive tool for early diagnosis of HSE extend and confirm previous results with PCR with HSV 2 as an etiological agent.
Abstract: A herpes simplex virus type 2 (HSV 2) etiology was sought in 93 consecutive cases of herpes simplex encephalitis (HSE) in immunocompetent post neonate patients. Antibodies to HSV 2 glycoprotein G antigen were determined by an enzyme-linked immunosorbent assay (ELISA) and HSV 2 DNA in cerebrospinal fluid (CSF) by a nested polymerase chain reaction (PCR) assay with primer pairs in the glycoprotein G gene. Evidence of HSV 2 infection was found in 6 patients; HSV 2 DNA was demonstrated in CSF and the intrathecal HSV 2 antibody response confirmed the findings. Five of the 6 patients with HSV 2 encephalitis presented a clinical picture, CSF, EEG, and CT findings characteristic of severe HSE. An atypically mild clinical course was seen in one patient. HSV 2 should be considered as an etiological agent in the viral diagnosis of HSE. With a combination of nested PCR assays for HSV 1 (primer pairs in the glycoprotein D gene) and HSV 2 in 10 microliters of CSF with no other preparation than freeze-thawing, HSV 1 or HSV 2 DNA was detected in 88 out of 93 (95%) of the first CSF specimens collected after the onset of neurological HSV disease. These findings extend and confirm previous results with PCR as a rapid and sensitive tool for early diagnosis of HSE.
249 citations
TL;DR: The observations suggest that measles virus is capable of causing persistent infection of the intestine and that Crohn's disease may be caused by a granulomatous vasculitis in response to this virus.
Abstract: Transmission electron microscopy was used to examine the microvasculature of perfusion-fixed tissues from Crohn's disease and control patients. Paramyxovirus-like particles, and inclusions consisting of condensations of nucleocapsid, in giant cells and endothelium at foci of vascular injury were identified in all 9 Crohn's disease patients. Tissues from patients with Crohn's disease were also examined by either in situ hybridisation (n = 10) or immunohistochemistry (n = 15), and compared to inflammatory and noninflammatory controls (n = 22). Hybridisation for measles virus N-protein genomic RNA was positive in all cases of Crohn's disease localising to foci of granulomatous vasculitis and lymphoid follicles. Positive immunohistochemical staining for measles virus nucleocapsid protein was positive in 13 of 15 patients with Crohn's disease, localising to foci of granulomatous inflammation. Hybridisation for measles virus RNA was positive in a minority of control intestinal tissues; viral inclusions were not seen ultrastructurally. Immunostaining was negative in control cases of intestinal tuberculosis. These observations suggest that measles virus is capable of causing persistent infection of the intestine and that Crohn's disease may be caused by a granulomatous vasculitis in response to this virus.
244 citations
TL;DR: The study showed the presence of intact viral genome, of the expected length of 170 kb, persisting as free extrachromosomal element in the HSB‐2 cells but not in patients' peripheral blood mononuclear cells, indicating that the viral sequences are linked to high molecular weight cellular DNA.
Abstract: Saliva and peripheral blood mononuclear cells from three patients, two with lymphoproliferative disorders and one suffering from multiple sclerosis, were examined for the presence of human herpesvirus-6 (HHV-6) genome by using the polymerase chain reaction and Southern blot analysis. The search for anti-HHV-6 antibodies, carried out in the sera of the same cases by an immunofluorescence assay, was negative in two cases at the lowest dilution used (1:40). These three patients had a high number of HHV-6 specific sequences in uncultured peripheral blood mononuclear cells, which are thought to be a normal site of viral latency although, in healthy individuals, the infected cells are extremely rare. In order to gain some insight into the state of the viral genome in this latent HHV-6 infection, we used pulsed field gel electrophoresis to separate HHV-6 DNA directly from HHV-6 (strain GS) infected HSB-2 cells and from the peripheral blood mononuclear cells of these three patients. Our study showed the presence of intact viral genome, of the expected length of 170 kb, persisting as free extrachromosomal element in the HSB-2 cells but not in patients' peripheral blood mononuclear cells. On the other hand, in strong contrast with the results obtained in infected HSB-2 DNA, the restriction analysis of the three patients' peripheral blood mononuclear cell DNA showed fragments of molecular weight constantly higher than the 170 kb segment, indicating that the viral sequences are linked to high molecular weight cellular DNA.(ABSTRACT TRUNCATED AT 250 WORDS)
178 citations
TL;DR: One of the important contributions of acyclovir was the demonstration for the first time that a compound could prevent the DNA replication of a DNA virus at concentrations far below those that affect cellular DNA synthesis.
Abstract: The reasons for acyclovir's activity and selectivity in cells infected with HSV or VZV may be summarized as follows: 1. Activation by a HSV- or VZV-specified TK. 2. Greater sensitivity of viral DNA polymerase than of the cellular polymerases to ACV-TP. 3. Inactivation of the viral DNA polymerase, but not the cellular polymerases, by ACV-TP. 4. Chain termination of viral DNA by incorporation of ACV-MP. For the Epstein-Barr virus, which is also sensitive to acyclovir, there is no selective activation in infected cells [Colby et al., 1981], but the viral polymerase can be inhibited by very low levels of ACV-TP [Datta et al., 1980]. For HCMV, the activation of acyclovir is very poor but the viral polymerase is also more sensitive to ACV-TP than the cellular polymerases. One of the important contributions of acyclovir was the demonstration for the first time that a compound could prevent the DNA replication of a DNA virus at concentrations far below those that affect cellular DNA synthesis. As we all know, in the past 15 years there has been a complete rejuvenation of antiviral chemotherapy. I think it is very fortunate that we changed our outlook on the possibility of making potent and selective antiviral agents in time so that, when the AIDS epidemic came along, we did not feel completely at a loss on ways to attack viral disease.
176 citations
TL;DR: Antibody capture radioimmunoassays were developed for detecting virus specific IgM (MAC‐Ria) and IgG (GACRIA) to measles, mumps, and rubella and used to investigate saliva as an alternative specimen to serum for diagnosis.
Abstract: Antibody capture radioimmunoassays were developed for detecting virus specific IgM (MACRIA) and IgG (GACRIA) to measles, mumps, and rubella and used to investigate saliva as an alternative specimen to serum for diagnosis. Saliva was collected from 63 patients with measles, 19 with mumps, and 150 with rubella, which were all clinically diagnosed and serologically confirmed. Virus specific IgM was detected in 92% of measles, 75% of mumps, and 100% of rubella saliva samples collected during the first week of illness. Between 1 and 5 weeks after onset virus specific IgM was detected in 100% of saliva specimens. After the 5th week the proportion of reactive specimens declined. The specificity of the MACRIA tests was established by testing saliva samples collected from blood donors for measles (88), mumps (88), and rubella IgM (91). All of the saliva specimens tested for measles and rubella specific IgM were unreactive, 1/88 specimens tested for mumps specific IgM contained significant reactivity. Saliva specimens collected from acute cases of MMR were tested in all 3 MACRIAs. A small proportion of saliva samples contained detectable IgM of more than one virus infection. Rubella and measles specific IgG was detected in the saliva of all cases from the 4th or 5th day of illness, respectively. Detection of mumps specific IgG was less successful. We have demonstrated that virus specific IgM can be reliably detected in saliva samples collected from acute cases of measles, mumps, and rubella and identified 1-5 weeks after onset of illness as the optimum time for collection of samples.
159 citations
TL;DR: Two hundred and twelve urine specimens, from several clinical groups, were examined for BK virus (BKV) using the polymerase chain reaction (PCR) to detect the VP1 region of BKV DNA.
Abstract: Two hundred and twelve urine specimens, from several clinical groups, were examined for BK virus (BKV) using the polymerase chain reaction (PCR) to detect the VP1 region of BKV DNA. Positive results were obtained on 14 specimens from 44 post-transplant patients (31.8%), 10 specimens from 39 pregnant women (25.6%), and 5 specimens from 100 children (5%) but not on any specimens from 29 laboratory staff. Twenty-eight of the amplified BKV genomes, 19 from urine specimens, eight from culture fluid of inoculated tissue, and also one from a throat washing were directly sequenced from single-stranded templates immobilized via a biotinylated primer; it was possible to assign all to one of the four subtypes of BKV which had previously been identified on the basis of variation in nucleotide sequence of the VP1 region. Serological subgroup classification correlated with the genomic subtyping results in 21 of the isolates. The distribution of the BKV subtypes and the clinical status of the infected individuals are discussed.
141 citations
TL;DR: DNA sequences for the VP1 gene which codes for the major capsid protein of BK virus (BKV) and may be responsible for antigenic variability were determined for seven BKV isolates and it is postulated that this region is the epitope responsible for serotypic differences between BK isolates.
Abstract: DNA sequences for the VP1 gene which codes for the major capsid protein of BK virus (BKV) and may be responsible for antigenic variability were determined for seven BKV isolates. The observed sequence differences and those previously reported correlate with the typing of isolates into four groups by haemagglutination inhibition. Amino acid coding alterations were found to be clustered within residues 61 to 83. Each antigenic group was found to have a characteristic amino acid sequence between residues 61 and 83. Several clones originating from a single isolate, although differing slightly in restriction enzyme digestion patterns, were found to be identical in this region. The VP1 sequences of three of the four groups were analysed by hydropathy plots and two hydrophilic areas of high antigenicity were identified. One of these corresponds to residues 61 to 83 and it is postulated that this region is the epitope responsible for serotypic differences between BK isolates.
115 citations
TL;DR: Preliminary studies indicate that the trpE‐C2 protein is a promising candidate HEV vaccine.
Abstract: Immunization of two cynomolgus macaques (cynos) with trpE-C2 protein, a trpE-HEV fusion protein that represents the carboxyl two thirds of the putative capsid protein, prevented development of biochemical evidence of viral hepatitis in these primates after challenge by wild-type HEV from either a Burmese or Mexican stool isolate. Neither of the immunized animals showed any elevation of alanine aminotransferase activity after challenge with wild-type HEV in marked contrast with the unimmunized (control) cynos. In the case of the Burmese HEV challenged cyno, the protective effect was complete with the animal failing to demonstrate any evidence of HEV infection. The immunized cyno challenged with Burmese HEV did not exhibit any HEV RNA in its stools or HEV antigen in its liver. The immunized cyno (#8902) challenged with Mexican virus exhibited HEV RNA in its stools and HEV antigen in its liver; however, microscopic examination of liver biopsy specimens from this cyno failed to detect histopathologic evidence of viral hepatitis. All of the animals (naive and immunized) developed anti-HEV IgM and IgG responses after HEV challenge. Our preliminary studies indicate that the trpE-C2 protein is a promising candidate HEV vaccine.
114 citations
TL;DR: Findings demonstrate that GACELISA HIV 1 + 2 tests on saliva or on urine are an accurate alternative to a conventional anti‐HIV test of blood.
Abstract: Epidemiological evidence and laboratory studies indicate that human immunodeficiency virus type 1 (HIV 1) is rarely, if ever, transmitted in saliva or urine. In that both specimens are easy to collect, each may be a useful alternative to serum specimens for anti-HIV screening. A rapid, simple, and robust IgG-capture enzyme-linked immunosorbent assay (GACELISA) suitable for the detection of anti-HIV 1 and 2 in saliva and urine was developed. Following optimisation of the assay, 177 salivary and 568 urine specimens collected from individuals of known serostatus were investigated. The assay was 100% sensitive on 50 salivary (median OD/CO = 8.9) and 126 urinary (median OD/CO = 8.6) specimens collected from anti-HIV-positive patients. The specificity was 100% on 127 salivary specimens (median OD/CO = 0.37) and 422 urinary specimens (median OD/CO = 0.39) collected from anti-HIV-negative individuals. These findings demonstrate that GACELISA HIV 1 + 2 tests on saliva or on urine are an accurate alternative to a conventional anti-HIV test of blood. This assay is satisfactory for surveillance purposes and, with appropriate precautions, could be used clinically.
103 citations
TL;DR: The results suggest that HCV prevalence and genotype distribution vary from region to region in China, and that the HCV now predominant in China may have evolved epidemiologically with infections in Japan and Taiwan.
Abstract: China has not been extensively investigated for the prevalence of hepatitis C virus (HCV) infection among people with or without liver disease. We analyzed serum from 2,177 liver disease patients from 7 cities in different areas of China. Of 435 acute hepatitis patients, only 11% were positive for HCV RNA, while hepatitis B surface antigen (HBsAg) was detected in 33%. Of 1,668 patients with chronic liver disease, 14% and 74% were positive for HCV RNA and HBsAg, respectively. Nearly 80% of non-B chronic liver disease were negative for HCV RNA. The frequency of HCV RNA in chronic liver disease was significantly higher in Hami (32%) and Shenyang (30%) than in other cities (6-12%). The HCV genotype distribution varied by region. Genotype III was detected in 46-70% of HCV infections in Hami, Shenyang, and Lanzhou, while more than 90% of patients from southern cities (Nanjing, Nanning, and Chengdu) had genotype II. No evidence for genotype I or IV infections was found. A full-length HCV genome sequence (HC-C2) derived from a Beijing patient with genotype II was closely related to previous isolates from Japanese and Taiwanese patients. These results suggest that HCV prevalence and genotype distribution vary from region to region in China, and that the HCV now predominant in China may have evolved epidemiologically with infections in Japan and Taiwan. The study identified a high frequency of non-B, non-C chronic liver disease in China, suggesting possibly a new agent or infections with extreme variants of HCV.
101 citations
TL;DR: The VV/SCID mouse model employed here may be useful for determining whether (attenuated) recombinant VV (carrying HIV genes) may have detrimental effects in the immunodeficient host and HPMPC may be considered as a drug candidate for the treatment and prophylaxis of such complications.
Abstract: Severe combined immune deficient (SCID) mice inoculated intravenously with vaccinia virus (VV) became sick within 6–8 days and died 10–12 days after infection. Tail lesions developed and the number depended on the virus inoculum. Age-matched immunocompetent NMRI mice similarly infected also developed tail lesions but did not become sick. When the infected SCID mice were treated with the acyclic nucleoside phosphonate HPMPC [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine], either for 5 consecutive days starting on the day of infection or for 5 consecutive days starting on day 2, 4, or 6 post infection, or as a single dose at 7 days or 1 day before infection, VV-associated death was significantly delayed. VV-infected SCID mice that received two doses of 20 mg/kg of HPMPC every week survived the infection for about 130 days. The period during which the mice remained disease-free following HPMPC treatment correlated with the absence of detectable virus in their organs. The VV/SCID mouse model employed here may be useful for determining whether (attenuated) recombinant VV (carrying HIV genes) may have detrimental effects in the immunodeficient host. HPMPC may be considered as a drug candidate for the treatment and prophylaxis of such complications.
TL;DR: PCR was found to be at least five times more sensitive than cell culture for the detection of PVs in these clinical specimens, and the overall rate of pathogen identification increased from 28% when only cell culture and serology were used to 57% when these methods were supplemented by PVnRT‐PCR.
Abstract: A seminested RT-PCR (nRT-PCR) was used to detect picornavirus (PV) RNA in cell cultures inoculated with rhinoviruses (HRVs) and enteroviruses (EVs). PCR tests in which a primary "touchdown" PCR was followed by secondary reactions using PV or HRV specific primers were able to differentiate HRVs of 48 serotypes from EVs. PVnRT-PCR and HRVnRT-PCR were then used to test nasal and throat swabs from adult subjects with naturally acquired respiratory virus infections. The swabs were also analysed for respiratory viruses by cell culture techniques and the rates of PV identification by the two methods were compared. PVnRT-PCR was found to be at least five times more sensitive than cell culture for the detection of PVs in these clinical specimens. Paired acute and convalescent serum samples were tested for complement fixing antibodies to adenovirus, influenza A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, and 3, Myco plasma pneumoniae, and Chlamydia psittaci. An enzyme-linked immunosorbent assay (ELISA) was used to detect rises in antibody level to coronavirus types 229E and OC43. The overall rate of pathogen identification in 159 swabs from adult asthmatics increased from 28% when only cell culture and serology were used to 57% when these methods were supplemented by PVnRT-PCR.
TL;DR: The introduction of new antivirals with enhanced lipophilicity and, potentially, greater activity in the central nervous system may further improve outcome from this devastating disease.
Abstract: Neonatal herpes simplex virus infections are a common problem in the United States, occurring at an incidence of one in approximately 3,500 deliveries In the absence of antiviral therapy significant morbidity and mortality is attendant with disease Disease manifestations in the newborn include multiorgan involvement (disseminated disease), encephalitis, and/or infection limited to the skin, eye, or mouth These three broad classifications provide distinctions in severity of disease for evaluation of outcome following antiviral therapy The availability of antiviral therapy for life-threatening disease, particularly that which is disseminated or involves the brain, has been of particular benefit for children with neonatal herpes Both acyclovir and vidarabine have proven effective in the management of neonatal herpes simplex virus infection With current therapeutic modalities, mortality from disease localized to the skin, eye, and mouth is virtually non-existent, yet a few children (approximately 5%) are still at risk for a long-term neurologic sequelae For babies with encephalitis, the mortality has been reduced to approximately 15% and nearly 50% of survivors develop normally 3 years after treatment Outcome with disseminated infection is of less value as mortality remains high (50%), but the number of survivors who develop normally is approximately 85% The introduction of new antivirals with enhanced lipophilicity and, potentially, greater activity in the central nervous system may further improve outcome from this devastating disease
TL;DR: A large number of cases from the epidemics were HEV, though a few remained undiagnosed, while of the sporadic cases only a few could be diagnosed as HCV or HEV; a large proportion remained und iagnosed.
Abstract: Non-A, non-B (NANB) hepatitis viruses are now classified as hepatitis E (enterically transmitted) and hepatitis C (parenterally transmitted). India experiences a large number of epidemics of the enteric disease every year. In addition, about 70% of the sporadic cases among adults are also due to NANB hepatitis. With the availability of an immunoblot assay for the detection of anti-HEV-IgM and the polymerase chain reaction (PCR) for the detection of HCV-RNA, serum samples from epidemic and sporadic NANB patients were screened for these markers. We found that a large number of cases from the epidemics were HEV, though a few remained undiagnosed, while of the sporadic cases only a few could be diagnosed as HCV or HEV; a large proportion remained undiagnosed.
TL;DR: The isolation of human herpesvirus 7 (HHV‐7) from saliva and blood, and the prevalence of antibodies to the virus in healthy individuals were investigated in Japan, and no simultaneous rise in the antibody titers was observed in 7 virologically confirmed exanthem subitum patients.
Abstract: The isolation of human herpesvirus 7 (HHV-7) from saliva and blood, and the prevalence of antibodies to the virus in healthy individuals were investigated in Japan. By cocultivating samples with phytohemagglutinin-P-stimulated cord blood mononuclear cells, HHV-7 was isolated from the saliva of 1 of 20 children and from 4 of 38 adults but not from their blood. The isolates were confirmed as closely related to RK strain of HHV-7, but not to U1102 (human herpesvirus 6, HHV-6 type A) or Z29 (HHV-6 type B) strains by restriction cleavage patterns of the DNA. The virus antibody of 330 healthy children and adults was measured with an indirect immunofluorescence assay, using one of our isolates (FG7-6). The positivity rate of antibody was 40% in the first 2 months of life, declined during the first 6 months, then gradually increased and was 45% at 1-4 years of age. It reached the highest level (60%) at 11-13 years of age and was maintained until the end of the third decade, then decreased thereafter. Additionally, no simultaneous rise in the antibody titers was observed in 7 virologically confirmed exanthem subitum patients.
TL;DR: The data presented in this study indicate that low avidity IgG to HHV-6 may be detected after primary infection and that this should prove useful in diagnosis and for seroepidemiological surveys.
Abstract: Sera from 321 children aged 0-179 weeks and 196 adult blood donors were examined for IgG antibodies to human herpesvirus-6 (HHV-6) using an indirect immunofluorescence test. After birth, antibody prevalence declined to a minimum between 20 and 29 weeks. Thereafter the percentage of individuals with antibody increased up to the age of 60-69 weeks after which the prevalence of antibody in the children remained stable at about 88%; in contrast, the seroprevalence in blood donors was 98%, indicating that some individuals remain susceptible to infection after early childhood but that virtually all are infected by the time they reach adulthood. The HHV-6 antibody titre increased steadily over the first 70 weeks of life and then remained stable up to 179 weeks old at a level significantly higher than that of the adults. Two hundred and eighteen of the 321 sera whose HHV-6 antibody titres were 40 or greater were tested for antibody avidity using a modification of the immunofluorescence test whereby low avidity antibody was eluted with urea. The results show that the age distribution of low avidity antibody closely parallels the known distribution of exanthem subitum and, moreover, that the mean antibody avidity increased with time after primary infection. The method was further validated because well-characterised convalescent sera taken from seven children within 3 weeks of exanthem subitum all contained low avidity antibodies. The data presented in this study indicate that low avidity IgG to HHV-6 may be detected after primary infection and that this should prove useful in diagnosis and for seroepidemiological surveys.
TL;DR: Human herpesvirus 7 (HHV-7) was isolated frequently from saliva specimens, indicating that infection of HHV‐7 occurs during early infancy and the virus shedding rate after infection is very high.
Abstract: Human herpesvirus 7 (HHV-7) was isolated frequently from saliva specimens. The isolation rates were 81% (13/16) in adults, 70% (7/10) in children over 1 year old, and none (0/7) in children less than 1 year old, respectively, indicating that infection of HHV-7 occurs during early infancy and the virus shedding rate after infection is very high. Human herpesvirus 6 (HHV-6) was not isolated from saliva specimens although some studies on isolation of HHV-6 from saliva was reported previously. © 1993 Wiley-Liss, Inc.
TL;DR: The survey found no discernible differences in LVA prevalence between males and females or among various age groups, and testing of hospital staff members of the eight central hospitals in these areas for LVA revealed a similar distribution of seropositivity among hospitals in various prefectures.
Abstract: More than 3,100 households in 27 selected villages distributed in the main geographic regions of Guinea were surveyed for the presence of Lassa virus-specific IgG antibodies (LVA), using an enzyme-linked immunosorbent assay (ELISA) with Lassa virus nucleocapsid protein expressed in insect cells infected with a recombinant baculovirus as antigen. The highest prevalence of LVA (25-55%) was found among inhabitants of tropical secondary forest (areas near Gueckedou, Yomou, and Lola) and guinea savannah (Faranah and Kindia areas), near the southern frontiers with Sierra Leone and Liberia. A much lower prevalence (4-7%) was found among inhabitants of mountainous (Pita, Labe, and Mali) and coastal (Boffa, Boke) areas. We found no discernible differences in LVA prevalence between males and females or among various age groups. Testing of 406 hospital staff members of the eight central hospitals in these areas for LVA revealed a similar distribution of seropositivity among hospitals in various prefectures. The highest prevalence of LVA in hospital staff (29-40%) was in the Gueckedou and Lola hospitals. Sera of LVA-positive persons were tested via Western blot analysis. Antibodies bound predominantly to NP and GP2 proteins.
TL;DR: Findings suggest that JEV persists in the nervous system of a small proportion of patients, as described in 16/323 laboratory‐confirmed cases of Japanese encephalitis.
Abstract: Immunological and virological evidence for persistence of Japanese encephalitis virus (JEV) in the human nervous system is described in 16/323 (5%) laboratory-confirmed cases of Japanese encephalitis. In 9/16 patients, JEV specific IgM antibodies were detected in the CSF even at 50-180 days after the onset of symptoms. Similarly, in 7/16 patients, apart from IgM antibodies, viral antigen was also present in the CSF beyond the third week of illness and in one patient it could be detected even at 117 days. Infectious virus could be isolated from the CSF beyond the third week of illness in 3/16 patients. In one patient, JEV was isolated from the CSF on three consecutive occasions at 90, 110, and 117 days after onset of clinical symptoms. These findings suggest that JEV persists in the nervous system of a small proportion of patients.
TL;DR: It is concluded that oral ribavirin seems to reduce the viral load, at least temporarily, in some patients with chronic viremic HCV infection.
Abstract: Ten patients with biopsy verified chronic hepatitis C virus (HCV) infection were treated with oral ribavirin at a dose of 1,000-1,200 mg per day in two divided doses for 12 weeks. Serum alanine aminotransferase (ALT) levels and hepatitis C viral ribonucleic acid (RNA) levels in serum were followed prior to, during, and 12 weeks posttreatment. ALT levels decreased significantly in all patients during therapy from a mean level of 3.21 mukat/l (range 1.22 to 7.79) before, to 1.25 mukat/l (range 0.78 to 2.04) at the end of treatment (P < 0.005). Hereafter, relapse to pretreatment levels was seen within 12 weeks after treatment stop. The hepatitis C viral RNA levels decreased from a mean 10 log titer of 4.1 (range 1-6) before treatment to 3.4 (range 1-5) at treatment stop. Five patients did not change their HCV RNA titers during treatment. Twelve weeks posttreatment only 3 patients had lower titers than prior to treatment. We conclude that oral ribavirin seems to reduce the viral load, at least temporarily, in some patients with chronic viremic HCV infection. Further studies are needed to evaluate fully the effect of oral ribavirin on chronic HCV infection.
TL;DR: A case of malignant lymphoma in which the virus infection was confined to epithelia of the renal calyces, renal pelvis, ureter, and urinary bladder is found, showing that BK virus is a human urotheliotrophic virus.
Abstract: By screening consecutive autopsy cases with an antibody that recognizes human polyomaviruses, we found a case of malignant lymphoma in which the virus infection was confined to epithelia of the renal calyces, renal pelvis, ureter, and urinary bladder. The virus was confirmed as BK virus by a specific monoclonal antibody against BK virus T antigen, and numerous virus particles were identified by electron microscopy. The results showed that BK virus is a human urotheliotrophic virus.
TL;DR: It is found that the median duration of pain in acyclovir recipients was 20 days vs. 62 days for their placebo counterparts and the absence of pain at the onset of cutaneous herpes zoster did not preclude its later development.
Abstract: The most frequent complication of herpes zoster is postherpetic neuralgia, usually defined as chronic pain in the area of the exanthem that persists for at least a month after the skin lesions have healed. Several clinical studies of acyclovir showed a reduction in severity and duration of acute pain, but provided no definitive data for chronic pain. In order to determine if acyclovir therapy could reduce chronic pain, we reanalyzed data from the largest U.S. placebo-controlled treatment trial of 187 immunocompetent persons with herpes zoster. By considering pain as a continuum, we found that the median duration of pain in acyclovir recipients was 20 days vs. 62 days for their placebo counterparts (P = 0.02). Thus, acyclovir has been shown to reduce chronic zoster-associated pain. We also noted that the absence of pain at the onset of cutaneous herpes zoster did not preclude its later development.
TL;DR: Zovirax (acyclovir, ACV) is now widely accepted as a safe and effective treatment for the management of herpes simplex virus infections in normal and immunocompromised patients.
Abstract: Zovirax (acyclovir, ACV) is now widely accepted as a safe and effective treatment for the management of herpes simplex virus (HSV) infections in normal and immunocompromised patients. However, a common concern with regard to the widespread use of any antimicrobial agent is resistance. The virus specific mechanism of action of ACV involves two virus encoded enzymes, thymidine kinase (TK) and DNA polymerase. Any alteration in the genes coding for these two enzymes would therefore be expected to confer resistance. The findings from two extensive resistance monitoring programs have shown that in immunocompetent patients receiving ACV for the management of acute HSV disease, the incidence of resistance is extremely rare. The situation in the immunocompromised is different. In this patient group HSV disease is severe and protracted often requiring prolonged therapy thus increasing the exposure of the virus to drug. As a result HSV isolates resistant to ACV have occasionally been recovered. Biochemical and genetic analysis of the resistant clinical isolates has shown that resistance in the most part is due to an inability of the virus to produce TK which mirrors the findings with cell culture derived resistant virus. Laboratory studies would indicate that TK-deficient virus would have little clinical impact. Significantly, resistance has rarely been attributed to alterations in the substrate specificity of TK or DNA polymerase. The biological significance of these mutants is unclear but to date there has been no evidence of transmission of resistant virus.
TL;DR: Using clinical specimens from 200 patients with suspected B19 infection, nested PCR was shown to have important diagnostic advantages over the detection of B19 specific antibodies, suggesting that on the basis of serological data as obtained with currently available test systems a considerable proportion of B 19 infections would be mis diagnosed.
Abstract: A nested primer PCR assay was developed to detect human parvovirus B19 in various clinical specimens in a routine diagnostic laboratory. Under optimized conditions the highly specific assay had a sensitivity of less than 10 genome units. For practical reasons, however, this sensitivity was adjusted to 10–100 virus genomes in diagnostic applications. Using clinical specimens from 200 patients with suspected B19 infection, nested PCR was shown to have important diagnostic advantages over the detection of B19 specific antibodies. The data suggest that on the basis of serological data as obtained with currently available test systems a considerable proportion of B19 infections would be misdiagnosed. Examples for the usefulness of the PCR assay in routine diagnosis are given. © 1993 Wiley-Liss, Inc.
TL;DR: Sexual transmission of hepatitis C virus (HCV) was studied between 104 anti‐HCV positive index cases who have attended the Oxford Haemophilia Centre and longstanding sexual partners.
Abstract: Sexual transmission of hepatitis C virus (HCV) was studied between 104 anti-HCV positive index cases (99 haemophilic men, five women) who have attended the Oxford Haemophilia Centre and 104 (98 female, 6 male) longstanding sexual partners. Ninety-one percent of the index cases were HCV RNA positive by the polymerase chain reaction (PCR) and 56% were anti-human immunodeficiency virus (HIV) positive. Three (2.9%) sexual partners (each a female partner of a different HCV RNA positive haemophilic man) were anti-HCV, and HCV RNA, positive. All had other risk factors for HCV infection. Of 59 partners who were tested for anti-HIV four (7%) were positive and only one of these was also anti-HCV positive. There was no association between HIV positivity in the index cases and HCV positivity in their partners. Our results confirm a low risk of sexual transmission of HCV.
TL;DR: A pilot study of chronic hepatitis C treatment was conducted in 14 patients, finding that Liver histology improved in all the patients and HCV‐RNA was not detectable in 3 of the 5 responders at the end of therapy while during follow‐up viral RNA became undetectable in the other 2 patients.
Abstract: A pilot study of chronic hepatitis C treatment was conducted in 14 patients (13 had chronic active hepatitis and 1 had liver cirrhosis). All patients were asymptomatic for the human immunodeficiency virus (HIV) type 1 (mean CD4 count of 584 ± 283 cells/mm3). Patients received 9 MU rlFN-α2A per day for three months. After this, patients received 9 MU three times weekly for three months, 6 MU for another three months on the same protocol, and finally 3 MU again three times weekly for the last three months. After the first month of ALT treatment in 9 patients (64%) returned to normal; a significant decrease in ALT levels was observed with respect to the pretreatment values (mean of 42 lU/l, range 15–75 vs 152 IUI, range 69–355; P < 0.01). Of the 9 patients who completed the treatment period, 5 had a complete response, and 4 of these 5 continued with normal ALT values during follow-up (sustained response) while the other patient relapsed within one month after cessation of therapy. The remaining 4 patients were non-responders (including one case with a break-through of the response). HCV-RNA was not detectable in 3 of the 5 responders at the end of therapy while during follow-up viral RNA became undetectable in the other 2 patients. 2/4 non-responder patients had detectable HCV-RNA during follow-up. Liver histology improved in all the patients. No changes were observed in the immunological status or HIV infection. © 1993 Wiley-Liss, Inc.
TL;DR: The results of the analysis of sera obtained from China and Greece suggested that the Hantaviruses prevalent in these countries are closely related to the Hantaan serotype, and an NEV-like reactivity was observed in Central and Northern European patients.
Abstract: Hantavirus nucleocapsid protein has previously been identified as the major antigen recognized by the humoral immune response in hemorrhagic fever with renal syndrome (HFRS). It was therefore considered to be a suitable antigen for the development of rapid and reliable immunodiagnostic assays. Genes encoding the nucleocapsid proteins of two Hantavirus strains, one of the Puumala serotype [nephropathia epidemica virus (NEV)] and the other of the Hantaan serotype were expressed in E. coli, and the expression products were used as diagnostic antigens in solid-phase enzyme immunoassays. The assays were used to detect IgG- and IgM-antibodies in sera of HFRS patients originating from different geographic regions (China, Germany, Greece, Yugoslavia, Scandinavia). ELISA was highly sensitive and proved to be superior to the indirect immunofluorescence assay. Both antigens were necessary to diagnose all HFRS cases originating from the different countries. Most of the sera revealed a predominant reactivity with either 1 of the 2 antigens, allowing the characterization of the etiologic virus as Hantaan-like or NEV-like. The results of the analysis of sera obtained from China and Greece suggested that the Hantaviruses prevalent in these countries are closely related to the Hantaan serotype. In contrast, an NEV-like reactivity was observed in Central and Northern European patients. In the sera of Yugoslav patients both reactivity patterns were found, suggesting that both virus types occur in the Balkan region.
TL;DR: An outbreak of an acute sporadic viral hepatitis occurring at three villages in the lower Shebli region of southern Somalia was studied, and 97.6% of afflicted patients who were examined 6–10 days after onset of jaundice developed either IgM or IgG anti‐HEV.
Abstract: An outbreak of an acute sporadic viral hepatitis occurring at three villages in the lower Shebli region of southern Somalia was studied. Sera were examined for antibodies to hepatitis E virus (HEV) antigen by a recently developed enzyme-linked immunosorbent assay. The prevalence of anti-HEV ranged from 77.8% to 94.0% among the three villages. Anti-HEV prevalence did not differ significantly with age or sex. HEV infections were widely distributed among all age groups, without a preponderance in any specific age category. Overall, 97.6% of afflicted patients who were examined 6-10 days after onset of jaundice developed either IgM or IgG anti-HEV.
TL;DR: The test is of value in the investigation of herpesvirus infections in transplant patients after excluding a cross-reaction from the low avidity antibodies generated in the primary CMV response and providing evidence of recurrent HHV-6 infection.
Abstract: A newly developed IgG antibody avidity test for human herpesvirus-6 (HHV-6) was used in a study of primary and recurrent HHV-6 antibody responses in immunocompromised solid organ graft recipients. In a primary HHV-6 infection low avidity antibody was detected which matured to high avidity within 5 months whereas, in contrast, high avidity antibody was found in three recurrent infections thus showing the ability of the test to discriminate between primary and recurrent infection in immunosuppressed patients. Six HHV-6 seropositive transplant patients who experienced a subsequent primary human cytomegalovirus (CMV) infection had high avidity concurrent HHV-6 antibody rises, thus excluding a cross-reaction from the low avidity antibodies generated in the primary CMV response and providing evidence of recurrent HHV-6 infection. Four further HHV-6 seropositive patients with proven primary Epstein-Barr virus (EBV) infection were also studied; in each of these cases high avidity HHV-6 antibody rises were seen likewise suggesting recurrent HHV-6 infection. The test is therefore of value in the investigation of herpesvirus infections in transplant patients.
TL;DR: It is suggested that an IgM response follows primary measles vaccination in the immunologically naive, an Igm response is absent on revaccination of those previously immunized, and an IgG response may follow clinical measles virus infection independent of prior immunization status.
Abstract: The use of IgM antibody detection for the classification of the primary and secondary measles antibody response in persons following primary and secondary vaccination and natural measles virus infection was examined. Of 32 nonimmune children receiving primary measles vaccination, 31 (97%) developed IgM antibodies, consistent with a primary antibody response. Of 21 previously vaccinated children with low levels of preexisting IgG antibodies who responded to revaccination, none developed detectable IgM antibodies, whereas 33 of 35 (94%) with no detectable preexisting IgG antibodies developed an IgM response. Of a sample of 57 measles cases with a prior history of vaccination, 55 (96%) had detectable IgM antibodies. Of these, 30 (55%) were classified as having a primary antibody response and 25 (45%) a secondary antibody response based on differences in their ratios of IgM to IgG antibodies. Differences in the severity of clinical symptoms between these 2 groups were consistent with this classification scheme. These findings suggest that 1) an IgM response follows primary measles vaccination in the immunologically naive, 2) an IgM response is absent on revaccination of those previously immunized, and 3) an IgM response may follow clinical measles virus infection independent of prior immunization status.