bluuebunny/crossref_metadata_2025 huggingface dataset:
Virus excretion and strain specific antibody responses after oral poliovaccine in previously immunised children
Authors: Roivainen Merja , Thodén Carl‐Johan , Stenvik Mirja , Pöyry Tuija , Hovi Tapani
Published: March 2007

A nation‐wide campaign with trivalent oral poliovirus vaccine was organized in Finland in February‐March 1985 in order to stop the unexpected outbreak of poliomyelitis. Excretion time of the vaccine viruses and antibody responses due to vaccination were studied in a group of healthy 6‐year‐old children who were classmates to one of the patients during the outbreak and who also had been screened for excretion of the epidemic poliovirus type 3 strain. While faecal excretion of at least one of the three vaccine virus serotypes was documented in all 19 children, only one throat specimen out of 106 studied was positive in the virus isolation test. The mean excretion times for types 1, 2, and 3 were 13, 21, and 21 days, respectively, and five children were still excreting a vaccine virus strain at 5 wk. Faecal excretion of the type 3 vaccine virus was not seen in children who had been excreting the epidemic type 3 strain 4 mo earlier. Excretion of a respective vaccine virus strain was usually well correlated to a booster response in serum neutralising antibodies to types 2 and 3 but not to type 1 poliovirus. A relatively high prevaccination antibody level did not always prevent the take of the corresponding vaccine virus strain. An increase in the level of neutralising serum antibodies towards at least one poliovirus serotype was observed in all but one of the 17 children studied. Antibody responses to the live vaccine strains were similar to those towards the corresponding nonattenuated strains while the absolute antibody titres against the epidemic P3/Finland/23127/84 strain remained relatively low in most sera studied. These results support the view that the 1984 poliomyelitis outbreak in Finland was caused by an antigenically unusual strain of P3. Regular poliovirus vaccines can, however, be used to improve the humoral immunity to these strains as well.
Peroxidase‐anti‐peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis
Authors: Yoo Jae Young , Howard Ruby , Waggoner Jeanne G. , Hoofnagle Jay H.
Published: March 2007

Liver biopsy specimens from 58 American patients with chronic type B hepatitis were investigated for the presence and distribution of the hepatitis B core (HBcAg) and surface (HBsAg) antigens by peroxidase‐anti‐peroxidase techniques. HBsAg was detected in 43 (77%) and HBcAg in 52 (90%) patients. HBcAg was present in 50 of 51 (98%) patients with hepatitis B e antigen (HBeAg) but in only two of seven (29%) of patients with antibody to HBeAg (anti‐HBe). There was no correlation between severity of hepatitis or height of aminotransferase activities and the amount of HBsAg or HBcAg in hepatocytes but there was a positive correlation between amount of HBcAg and height of HBV‐DNA and DNA polymerase activity in serum. Follow‐up liver biopsies, taken 1 to 3 yr later, were available from 39 patients. HBcAg remained detectable in 25 of 26 patients with persistence of HBeAg but disappeared in 12 patients who had lost HBeAg.

In nine patients, HBcAg was cytoplasmic as well as nuclear in distribution. Seven of these patients had an intense lobular hepatitis with marked elevations in aminotransferase activities. These findings indicate that the amount of HBcAg in liver correlates with the amount of serum hepatitis B virus as quantified by serum levels of DNA polymerase and HBV‐DNA. The amount of nuclear HBcAg does not correlate with the severity of the liver disease, but the presence of cytoplasmic HBcAg usually reflects an active and severe ongoing hepatitis.
Inactivation of 1015 chimpanzee‐infectious doses of hepatitis B virus during preparation of a heat‐inactivated hepatitis B vaccine
Authors: Lelie P. N. , Reesink H. W. , Niessen J. , Brotman B. , Prince A. M.
Published: March 2007

The safety of a plasma‐derived hepatitis‐B vaccine inactivated by two heating steps (90 sec at 103 °C followed by 10 hr pasteurization at 65 °C) was validated in chimpanzees; 103 chimpanzee‐infectious doses (CID50) of hepatitis‐B virus (HBV), subjected to the purification steps during production of the vaccine, were noninfectious in two chimpanzees. Furthermore, 106 CID50 of HBV heated at 103 °C for 90 sec and another l06 CID50 of HBV heated at 65 °C for 10 hr, were also not infectious in two other chimpanzees. All animals developed hepatitis‐B infection after subsequent challenge with the untreated starting material, before the respective purification and inactivation procedures. Thus, the total reduction of infectivity of HBV during production of this vaccine was established to be at least 1015 CID50.
An outbreak of gastroenteritis in a home for the elderly associated with astrovirus type 1 and human calicivirus
Authors: Gray J. J. , Wreghitt T. G. , Cubitt W. D. , Elliot P. R.
Published: March 2007

We describe an outbreak of gastroenteritis, which lasted for 22 days in a residential home for the elderly. The outbreak was biphasic and affected 34/42 (80%) residents and 13/29 (44%) members of the staff. Calicivirus was associated with cases of illness during the first 9 days of the outbreak, and astrovirus type 1 with cases arising between days 16 to 22. Although the symptoms were generally mild, the resources required and the inconvenience caused were considerable.
Immunogenicity of low doses of hepatitis B vaccine in children: A study in 650 New Zealand children
Authors: Milne Alexander , Dimitrakakis Mary , Allwood Geoffrey , Lucas Ron , Moyes Chris , Pearce Neil
Published: March 2007

Six hundred and fifty New Zealand children from 2–12 years of age were vaccinated three times with 2 mcg intramuscular (IM) doses of Merck Sharp and Dohme plasma‐derived hepatitis B vaccine (H‐B‐Vax), at 0, 1, and 6 months, and tested 2‐‐3 months later for antibody to hepatitis B surface antigen (anti‐HBs) by radioimmunoassay (RIA). Overall, 96.5% of the children seroconverted for anti‐HBs by RIA, having levels greater than 2.1 RIA S/N units, with 91.2% having values greater than 10 S/N units. Anti‐HBs levels were also determined by enzyme immunoassay (EIA), by which method a significantly better response was demonstrated in 24‐year‐olds than in older children. This study demonstrated that a satisfactory anti‐HBs response was obtained using one‐fifth of the recommended doses of hepatitis B vaccine.
BK virus infection in children with cancer: Serological response studied by haemagglutination inhibition, neutralization, and IgG‐ and IgM‐class specific ELISA tests
Authors: Flaegstad Trond , Traavik Terje , Kolmannskog Svein , Stokland Tore
Published: March 2007

We recently developed enzyme‐linked immunosorbent assays (ELISAs) for the detection of anti‐BK virus IgG‐ and IgM‐antibodies, and also a convenient and rapid serum neutralization test. Complemented by a traditional haemagglutination inhibition test (HAI) these methods were used to investigate the longitudinal response to BKV infection in sequentially taken sera from 29 children under treatment for cancer.

In separate experiments it was shown that the results were not at any extent influenced by antibodies against other polyomaviruses.

At the time of diagnosis the prevalence of specific IgG‐ and IgM‐antibodies and the geometric mean IgG levels were not significantly different for the patients compared with a group of healthy children. The primary infections seemed to occur at the same age for the two groups of children.

Seven of the patients had a primary infection with BKV. The results indicate that the host response in moderately immunosuppressed children during primary infection is the same as expected for healthy individuals with the development of specific IgG, HAI, and NT antibodies, and, usually, production of BKV‐IgM for several months. The results indicated that whether specific IgM was demonstrated in the first sample or appeared later during a reactivation episode, this parameter was correlated with profound immunosuppression.

Significant titre changes, detectable IgM antibodies and/or seromnversions were demonstrated in 69% (20/29) of the cancer patients. Such indications of recent viral activity was recorded in 42% (S/i9) of chifdren with meningococcal infections. The observation periods for the two groups of patients are, however, not directly comparable.
Humoral and cellular immunity to papillomavirus in patients with cervical dysplasia
Authors: Cubie Heather A. , Norval Mary
Published: March 2007

The cell‐mediated and humoral immune responses to human papillomavirus (HPV) were tested in groups of patients with various degrees of cervical intraepithelial neoplasia (CIN) using a lymphocyte proliferation assay (LPA) as a measure of circulating sensitised T‐cells and an enzyme‐linked immunosorbent assay (ELISA) for antibodies.

Twenty‐three of 92 patients (25%) gave stimulation indices (S.I.) greater than two to at least one of the several antigen preparations tested in the LPA. Of 282 patients, 144 (50.1%) showed ELISA indices (E.I.) greater than one to HPV‐1 and/or HPV‐2 antigens prepared by disruption of purified virions.

No correlation was found between positive responses in either test and the presence in cervical biopsies of koilocytes (considered pathognomonic for HPV infections), or between positive responses and the degree of dysplasia observed. Rather, positive antibody and T‐cell responses corresponded with a history of past or present skin warts. Although antibody was detected in 42/86 (48.8%) women who thought they had never had warts, only 2/24 (8.3%) with no known history gave a positive S.I. in LPA.
Confirmation of HIV seropositivity: Comparison of a novel radioimmunoprecipitation assay to immunoblotting and virus culture
Authors: Tersmette M. , Lelie P. N. , van der Poel C. L. , Wester M. R. , de Goede R. E. Y. , Lange J. M. A. , Miedema F. , Huisman J. G.
Published: March 2007

A recently developed radioimmunoprecipitation assay, using 125I‐labeled human immunodeficiency virus (HIV) viral proteins enriched for glycoproteins gp120env, gp41env (GRIPA), was compared to the immunoblot assay with respect to sensitivity and specificity for the detection of antibodies to HIV. Longitudinal sets of serum samples of seroconverting homosexual men were studied, as were sera of six blood‐bank donors likely to be false‐positive in immunoblot. In addition, HIV isolation was attempted from white blood cells of these blood‐bank donors and of seropositive and seronegative individuals. In sets of seroconversion samples, the GRIPA appeared at least as sensitive as the immunoblot. Some sera already were clearly positive in the GRIPA at a time when there was only weak reactivity in immunoblot. In contrast, sera from blood‐bank donors that were regarded as false‐positive in immunoblot were negative in GRIPA. Virus culture from these donors was also negative. It is concluded that reactivity in immunoblot to core proteins only may well be false‐positive, whereas antibody reactivity in the radioimmunoprecipitation assay to p24gag solely suggests ongoing seroconversion. This feature, in addition to a sensitivity for anti‐gp120env comparable to immunoblotting, makes the GRIPA a useful confirmatory assay in sera that yield conflicting results in other HIV‐antibody assays.
Antibodies recognizing human serum albumin are not elicited by immunization with preS2 sequences of the hepatitis B virus envelope protein
Authors: Neurath A. Robert , Strick Nathan , Parker Karen , Kent Stephen B. H.
Published: March 2007

Antibodies to the preS2 region of the hepatitis B virus (HBV) envelope protein and to human serum albumin (HSA) were allegedly detected at about the same level in sera of humans with acute or chronic hepatitis B [Hellström et al., 1986]. It was claimed that anti‐HSA arises as a result of an immune response to the preS2 sequence and that it was involved in hepatocellular damage. Over 100 sera from animals and humans immunized with HBsAg containing preS2 sequences, or with synthetic peptides from the preS1, preS2, and S regions of the HBV env protein were assayed for anti‐HSA. The results revealed the following: 1) Immunization with the native preS2 sequence or with unconjugated synthetic peptides derived from that sequence does not result in elicitation of anti‐HSA. Therefore the alleged appearance of anti‐HSA during hepatitis B cannot be directly related to an anti‐preS2‐specific immune response. 2) Some synthetic peptides, whether or not they were derived from the preS2 sequence, when linked to certain carriers, but not to others, elicited in rabbits an anti‐HSA response, which was markedly lower than the response to the homologous peptide. These anti‐HSA antibodies could be separated from anti‐preS2‐specific antibodies by affinity chromatography and did not recognize the synthetic peptide used for immunization. The use in active immunoprophylaxis of hepatitis B of unconjugated peptides from the preS2 sequence with proven high immunogenicity will avoid carrier/linker‐mediated induction of antibodies not relevant to protection against HBV.
Diagnosis of fetal rubella infection by nucleic acid hybridization
Authors: Ho‐Terry L. , Terry G. M. , Londesborough P. , Rees K. R. , Wielaard F. , Denissen A.
Published: March 2007

The efficacy of nucleic acid hybridization for the diagnosis of rubella infection in experimental and clinical materials was compared with immunoblot and virus isolation techniques. Our results showed that nucleic acid hybridization is specific and rapid but gives false‐negative results when compared with conventional virus isolation in some experimental although not in clinical materials so far examined. For this reason, a failure to demonstrate rubella virus in fetal specimens by this method alone cannot yet be taken as a sole criterion for ruling out fetal rubella infection.
Characterization of BK virus‐specific antibodies in human sera by Western immunoblotting: Use of a zwitterionic detergent for restoring the antibody‐binding capacity of electroblotted proteins
Authors: Christie Karen Elina , Flaegstad Trond , Traavik Terje
Published: March 2007

After initial problems related to denaturation of antigenic epitopes, we developed a Western immunoblotting method for the characterization of antibodies reacting with BK virus (BKV) structural polypeptides. When a zwitterionic detergent, Empigen BB, was added to the running buffer during electroblotting, the antibody‐binding capacity of electrophoretically separated BKV polypeptides was partially restored. Antibodies reacting with different BKV antigens were detected and visualized by biotinylated anti‐species‐specific antibodies, peroxidase‐conjugated streptavidine, and diaminobenzidine staining.

Human sera containing anti‐BKV antibodies reacted with VP1, but a serum containing antinuclear antibodies also reacted with VP4, ‐5 and ‐6 (histones). Serum from a rabbit inoculated with purified BKV reacted with VP1, and also with VP4, indicating that BKV inoculation may imply production of antibodies against histones.
Molecular epidemiology of two consecutive outbreaks of adenovirus 8 keratoconjunctivitis
Authors: Chastel C. , Adrian T. , Demazure M. , Legrand‐Quillien M. C. , Lejeune B. , Colin J. , Wigand R.
Published: March 2007

Eleven strains of adenovirus 8 (Ad 8) isolated during two consecutive outbreaks of epidemic keratoconjunctivitis (EKC) in the Ophthalmology Department of a University Hospital in France were compared by DNA restriction analysis. The results indicated that isolates from the two outbreaks belong to the same genome type, which is also the most predominant genome type of Ad 8. The usefulness of molecular epidemiology in Ad 8 infections is briefly discussed.
Hepatitis B core antigen in serum during acute hepatitis B
Authors: Chemello L. , Pontisso P. , Schiavon E. , Thiers V. , Tagariello G. , Albert A.
Published: March 2007

Hepatitis B core antigen was measured in sera of patients with acute and chronic hepatitis B virus infection by a modified radioimmunoassay based on high molarity treatment of samples to avoid masking of antigen by homologous antibody. A good correlation between hepatitis B core antigen levels and serum HBV‐DNA was observed in sera obtained during chronic infection. In contrast, acute phase sera were often HBcAg positive but HBV‐DNA negative, particularly when obtained during maximum liver damage. Sequential studies in 5 patients with acute hepatitis B showed that HBcAg positivity persisted beside HBV‐DNA clearance and was often enhanced at the time of maximum liver damage, suggesting release of antigen from infected hepatocytes undergoing immunolysis, even after termination of virus replication.
Chronic enteric virus infection in two T‐cell immunodeficient children
Authors: Wood D. J. , David T. J. , Chrystie I. L. , Totterdell B.
Published: March 2007

Enteric virus infections were studied in two children with congenital T‐cell immunode‐ficiency. One patient (LC) with cartilage hair hypoplasia developed persistent diarrhea and malabsorption following acute gastroenteritis. Electron microscope (EM) examination of feces revealed excretion of rotavirus for more than 450 days with concurrent astrovirus infection for at least 225 days, associated with the persistent diarrhea. Prolonged infection with poliovirus type 2 following vaccination had previously been noted in this patient. The second patient (DT), with the CHARGE association and DiGeorge syndrome, had two episodes of loose stools. EM of fecal extracts demonstrated rotavirus excretion for at least 66 days following the initial episode.

Virus‐specific immune responses were assayed in these two patients. LC showed a poor serum neutralizing antibody response to poliovaccination, no detectable antibody response (by immune EM and ELISA) to rotavirus, and no detectable antibody response to astrovirus (by immune EM). Rotavirus specific cell mediated immunity was also not detectable. DT showed no detectable serum antibody response to rotavirus (by ELISA). Rotavirus isolates from both patients were found to be group A viruses and were further analyzed by polyacrylamide gel electrophoresis. Atypical genome profiles, with multiple additional bands between segments 3–7 of the normal rotavirus profile, were obtained throughout the course of each illness, including the earliest specimens available (day 41, LC; day 7, DT).

These results indicate that chronic virus infection of the gut can occur in patients with T‐cell immunodeficiency. Such chronic infection may be associated with persistent diarrhea and can cause considerable problems of management.
Cytomegalovirus‐specific antibody responses in renal transplant patients with primary and recurrent CMV infections
Authors: O'Neill H. J. , Shirodaria P. V. , Connolly J. H. , Simpson D. I. H. , McGeown Mary G.
Published: March 2007

Cytomegalovirus (CMV) specific immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody responses were measured before and after renal transplantation in 20 patients with primary CMV infection and in 16 patients with recurrent CMV infection. In primary CMV infection IgG antibody titres to late antigen (IgG‐LA) measured by indirect fluorescence (IFA) were approximately seven times higher than those obtained by the complement fixation test (CFT). In contrast, in recurrent CMV infection this difference was found to be about twofold. Virus‐specific IgM antibody to late antigen (IgM‐LA) was detected in 100 percent of patients with primary CMV infection and in only 50 percent of patients with recurrent CMV infection. The IgM‐LA titres were highest in primary CMV infection and reached peak levels at approximately 10 weeks post transplantation, whereas in recurrent CMV infection the IgM‐LA titres were lower and reached peak levels at three months post transplantation. Moreover, IgM‐LA was found to persist in patients from both groups at nine months post transplantation. IgM antibody to early antigen (IgM‐EA) was not detected in any patient in this study. However, significant fourfold titre rises in IgG antibody to EA (IgG‐EA) were detected in 100 percent of patients with recurrent CMV infection and in 50 percent of patients with primary CMV infection. These results clearly show the difference in antibody responses to the various antigens of CMV in patients with primary and recurrent CMV infection.
Development of a lymphocyte transformation assay for rotavirus in whole blood and breast milk
Authors: Totterdell B. M. , Patel S. , Banatvala J. E. , Chrystie I. L.
Published: March 2007

A multivariate assay was developed for detecting lymphproliferative responses to rotavirus in whole blood and breast milk. Detection of lymphocyte transformation in samples from healthy uninfected adults required an assay incorporating a large number of antigen and cell concentrations and several incubation periods before pulsing. In contrast, lymphoproliferation to rotavirus was observed over a wider range of these variables in blood collected from a kidney recipient nine days post‐rotavirus infection. Lymphoproliferation to rotavirus was detected in 32.5% of breast milk samples tested. The magnitude of lymphoproliferation to rotavirus did not correlate with rotavirus‐specific IgG ELISA antibody titres in sera or with rotavirus‐specific IgA ELISA antibody titres in breast milk.
Failure of influenza vaccination in the aged
Authors: Keren Gershon , Segev Shlomo , Morag Abraham , Zakay‐Rones Zichria , Barzilai Asher , Rubinstein Ethan
Published: March 2007

A cohort of 127 nursing home residents aged 60–98 years were vaccinated during the winter of 1985–86 with the A‐Chile 1/83 (C), A‐Philippines 2/82 (P), and B‐USSR (B) commercial influenza vaccines. Before vaccination 40%, 23%, and 69% were susceptible to influenza Ac, Ap, and B, respectively [hemagglutinin inhibition (H.I.) titer <1:40]. One month following initial vaccination, 32 patients [25%] remained unprotected against two or all three vaccine strains. These patients were revaccinated with the same influenza vaccine and followed up. At five months 11 %, 19%, and 23% of the initial cohort were still unprotected against Ac, Ap, and B strains, respectively. We conclude that two conventional influenza vaccines administered one month apart leave unprotected 30% of healthy elderly people who are initial influenza vaccine failures.
The morphology of human immunodeficiency virus (HIV) by negative staining
Authors: Chrystie I. L. , Almeida June D.
Published: March 2007

We have examined preparations of human immunodeficiency virus 1 (HIV‐1) and HIV‐2 by negative staining electron microscopy. HIV‐2 cultures contained large numbers of 130–200 nm particles containing a 130‐nm‐long by 30–70 nm‐wide core. This core is probably of conical or pear‐shaped morphology. Some particles exhibited a short fringe that could be seen to comprise a regular arrangement of repeating subunits when visualised end on. Identical particles were found in HIV‐1 cultures but in much lower numbers. Attempts to carry out negative staining immune EM were unsuccessful.

Also detected in both HIV‐1 and HIV‐2 cultures were small (70–80 run) fringed viruslike particles. The possible significance of these particles is discussed.
In vivo expression of rubella antigens on human leucocytes: Detection by flow cytometry
Authors: O'Shea Siobhan , Mutton David , Best Jennifer M.
Published: March 2007

Flow cytometry has been used to detect in vivo expression of rubella antigens on human leucocytes. Sequential samples of peripheral blood were obtained from four volunteers with naturally acquired rubella and five persons immunised with RA27/3 rubella vaccine. Leucocytes were stained for rubella antigens using a pool of rubella monoclonal antibodies. Rubella antigens were detected on the leucocytes of all four volunteers with naturally acquired rubella between 1 and 13 days after onset of illness. Viral antigens were expressed more frequently on the monocyte (9–51 %) than the lymphocyte (< 1–4%) and granulocyte (< 1–3 %) populations. Among the vaccinees, rubella antigens were detected on the leucocytes of four of the five volunteers between 5 and 12 days after immunisation. The expression of viral antigens was more transient and the proportion of cells exhibiting rubella‐specific fluorescence considerably lower following vaccination (1–12 %) than natural infection (9–51 %).

Our results demonstrate that flow cytometry provides a rapid and sensitive analytical technique for detecting viral antigens on leucocytes from infected persons. Leucocytes may play an important role in the pathogenesis of rubella infection.
Change in immune response to hepatitis B in boys with haemophilia
Authors: Williams M. D. , Boxall Elizabeth H. , Hill F. G. H.
Published: March 2007

Eleven of 27 haemophilic boys who received a common batch of Factor VIII concentrate subsequently developed acute hepatitis B; although 9 were considered not to have been previously exposed to the virus, 2 other boys had been considered immune to hepatitis B. The amount of concentrate received by each child, together with their HIV‐antibody status and T‐lymphocyte subset distribution prior to exposure, did not influence their response to the hepatitis B virus (HBV). The two previously immune children who became infected, however, had evidence of the HIV‐associated persistent generalized lymphadenopathy syndrome. Detailed investigation of the suspect batch of concentrate revealed hepatitis B surface antibody to a titre of 112 miu/ml, but surface antigen was not detectable, even after dissociation of antigen and antibody.

As a result of this outbreak, 5 of the 11 boys remain carriers of the virus and 2 other family members have contracted acute hepatitis B. The possibility that the response of the haemophiliacs to HBV may be altered due to acquired alteration of their immune function is discussed. Regular screening of haemophiliacs, including those immune to hepatitis B, is recommended, since even with regular donor screening, HBV remains a major infective risk to haemophiliacs receiving Factor VIII replacement therapy, and the risk to an individual may change with time.
Low incidence and high titers of antibodies to hepatitis B virus X‐Protein in sera of chinese patients with hepatocellular carcinoma
Authors: Liang X.‐H. , Stemler M. , Will H. , Braun R. , Tang Z.‐Y. , Schröder C. H.
Published: March 2007

Sera of patients from China with hepatocellular carcinoma (HCC) were tested for the presence of HBc/HBe− and HBx antibodies by immunoblotting using recombinant MS2 or β gal fusion proteins as substrate. Antibodies against HBx were detected in four out of 68 HBsAg positive and in one out of three HBsAg negative sera, antibodies against HBc/HBe in 52 and two serum samples, respectively. Competition experiments in which sera were preincubated with individual viral proteins synthesized in E. coli were carried out to demonstrate the specificity of signals obtained in immunoblot analyses. In the five anti‐HBx positive sera, the antibody titer against X fusion protein was higher than against core fusion protein and in one of these sera anti‐x activity could be demonstrated even at a serum dilution of 1:50,000. These data indicate that X antibodies occur rarely in Chinese patients and are not serodiagnostic for HCC. The high titer of X antibodies in some patients shows that the X protein can be highly immunogenic in vivo. Induction of antibody formation may be triggered by X protein expressed from integrated viral DNA.
Laboratory and epidemiologic assessment of a recent influenza B outbreak
Authors: King James C. , Haugh Connor J. , Dupont William D. , Thompson Juliette M. , Wright Peter F. , Edwards Kathryn M.
Published: March 2007

A viral surveillance system in Nashville detected an outbreak of influenza B that occurred between January and March 1986. Paired sera from 32 individuals with culture‐documented influenza B illness were tested using three serologic assays. Enzyme‐linked immunosorbent assay (ELISA) using purified hemagglutinin‐neuraminidase and plaque neutralization detected a seroresponse in 69% and 66% of these individuals, respectively. These assays were superior to hemagglutination inhibition, which detected a 41% seroresponse. ELISA was preferred because of cost and ease of performance.

A group of 286 individuals, aged 1–65 years, was studied more extensively including serologic assessment before and after the influenza B outbreak. Historical information and viral throat cultures were obtained from those with influenza‐like illness during the epidemic. An influenza B infection rate (seroresponse and/or positive culture) of 31% and illness rate (infection with flu‐like symptoms during the epidemic period) of 13% was demonstrated using these methods. Pre‐epidemic mean serum ELISA IgG titers were lower in those with, versus those without, evidence of subsequent influenza B illness (1,541 vs. 4,311, P = .0026). Children ≤ 15 years of age were infected more frequently than adults (44% vs. 28%, P = .04). Fever ≥ 101°F was reported more frequently with influenza B than non‐B illness (43% vs. 18%, P = .03).

These data are useful in preparing for future epidemiologic studies of influenza B and demonstrate the value of and need for standardization of ELISA as a serologic assay for influenza B.
Virus isolation and immune studies in a cohort of homosexual men
Authors: Buimovici‐Klein Elena , Lange Michael , Ong Kenneth R. , Grieco Michael H. , Cooper Louis Z.
Published: March 2007

Virus shedding was detected in 77% of homosexual subjects and in only 6% of heterosexual controls. The overall virus isolation rate in homosexual subjects was not significantly different among HIV‐seropositive (79%) and HIV‐seronegative (74%) individuals. In about 20% of homosexual subjects, virus shedding from multiple sites was observed. The most frequently isolated virus was cytomegalovirus (CMV) (41%), followed by enteroviruses (23%), herpes simplex virus (HSV) (7%), and adenoviruses (6%). In the control group, about 50% of subjects were seronegative for HSV‐1 and 2, and about 70% were negative for CMV and Epstein‐Barr virus (EBV). Only 2% of homosexuals were seronegative for CMV, about 5% for HSV‐1 and 2, and about 20% for EBV. No differences were found in antibody levels against varicella‐zoster virus (VZV) among the control and homosexual groups. The proportion of seronegatives for Coxsackie and hepatitis viruses was significantly higher in control than in homosexual subjects. However, no differences in the proportion of seronegatives for measles, mumps, and rubella were observed. No HIV‐antibody‐negative individual was detected with an OKT4/OKT8 ratio of less than 0.75. On the other hand, only HIV‐positive subjects, with a ratio of less than 0.75, had high serum IFN alpha titers. The results suggest that the high rate of virus shedding among HIV‐negative homosexual subjects might be a factor in the development of AIDS in this high‐risk population.
Detection of anti‐delta antibodies among acute hepatitis B virus‐infected patients
Authors: Tswana Sam A. , Laher Sarah
Published: March 2007

A total of 130 acute HBsAg‐positive subjects were tested for the presence of delta hepatitis antibodies (anti‐HD). Of the 130 subjects, 56 were females and 74 were males. All patients were individuals attending the two teaching hospitals, i.e., Parirenyatwa and Harare Central hospitals.

All the sera were examined by the enzyme‐linked immunosorbent assay (ELISA), and results were read spectrophotometrically at a wavelength of 492 nm. Of 130, 11 (19.64%) males had anti‐HD present in the serum with an overall prevalence of 21 (16.15%).

The positivity rates of HBeAg and anti‐HBc were 64 (49.23%) and 116 (89.23 %), respectively. There was no significant difference between the positive rate in males as compared to females.
Influence of hepatitis delta virus superinfection on the clearance of hepatitis B virus (HBV) markers in HBV carriers in Japan
Authors: Ichimura Hiroshi , Tamura Ikuo , Tsubakio Tadahiro , Kurimura Osamu , Kurimura Takashi
Published: March 2007

To elucidate the influence of hepatitis delta virus (HDV) superinfection on the clearance of hepatitis B virus (HBV) associated antigens in HBV carriers, we examined for antibody to hepatitis delta antigen (anti‐HD) serial sera collected from 1,029 HBV carriers in Kure, Japan. Of the 242 HBV carriers with hepatitis B e antigen (HBeAg), 28 became seropositive for anti‐HD, of whom 18 (64.3%) cleared HBeAg; 214 did not become seropositive for anti‐HD, of whom 70 (32.7%) cleared HBeAg. Thus, HBeAg clearance was observed in a significantly higher proportion of HDV‐superinfected carriers as compared with carriers with‐ out HDV infection (P< 0.005). In the 56 HBV carriers who cleared hepatitis B surface antigen (HBsAg), anti‐HD was detected in three cases with increased serum alanine aminotransferase activity preceding HBsAg clearance. The duration of anti‐HD seropositive state was less than 5 years, and the titer of anti‐HD was relatively low in every case. These data suggest that the HDV infection rate in Japan is higher than previously reported, that HDV superinfection can be one of the factors that induce the HBeAg clearance and HBsAg clearance in HBV carriers, and also that the most likely outcome of HDV superinfection in HBV carriers in Japan may be acute self‐limited infection.
New and sensitive standard cell culture technique for the detection of cytomegalovirus in clinical specimens
Authors: Agha S. A. , Coleman J. C. , Mahmoud L. A. , Abd‐Elaal A. M. , Selwyn S.
Published: March 2007

Conventional tube cell culture has been recognised as the most sensitive technique available for human cytomegalovirus (HCMV) detection. Low‐speed centrifugation of specimen inocula onto cell culture monolayers has been shown to increase the efficiency of infection with the AD 169 strain of HCMV. Therefore a centrifugal force of 900g for 1 hour at 37°C was used to enhance the detection of HCMV cytopathic effect (CPE) in shell vials that contained circular coverslips with a monolayer of human embryonic lung (HEL) fibroblasts. Of 195 specimens, HCMV CPE was detected in 18 specimens (9.02%) on shell vial culture assay, whereas conventional tube cell culture was positive in only 13 specimens (6.6%). The shell vial culture assay was significantly more sensitive (P< 0.05). Furthermore the development of the cytopathic effect on shell vial culture assay was significantly earlier (P < 0.01) and more extensive. Urine samples were sonicated and the results obtained with immunofluorescence using human immune serum demonstrated that sonication increased both the intensity of fluorescence and number of fluorescent foci of HCMV‐infected cells and also decreased the nonspecific fluorescence of the background.
Monte Carlo simulation of the heterosexual selective spread of the human immunodeficiency virus
Authors: Barrett John C.
Published: March 2007

The spread of human immunodeficiency virus (HIV) by heterosexual intercourse, during the first 2 years following the introduction of the virus among a sexually active and unprotected group of men and women, is modelled by Monte Carlo simulation. A beta distribution of the infectee's risks of infection per infected partner‐month is assumed, with the same coefficient of variation as used in previous studies for risk of conception (natural fecundability), but with a mean of 0.04 per infected partner‐month, after scaling the distribution. The number of sexual partners that one sex has (here, the women), is assumed to be more variable than for the other, with a mean of 2 partners each. The individual infection risks per infected partner‐month are generated initially and do not change, but some random gains and losses of partners occur each month. Infections are updated each month. It is found in this simple model that women who become infected by 2 years had a mean risk of infection (not counting the original infector) only about 13% higher than the others. Some implications of the low selection are noted. Very great variability in the number of infections subsequently due to an index seropositive is found, which prevents easy discrimination in the characteristics of “at‐risk” persons.
Hematologic dysfunction in Lassa fever
Authors: Fisher‐Hoch Susan P. , McCormick J. B. , Sasso D. , Craven R. B.
Published: March 2007

Lassa fever is widespread in West Africa, where the case fatality is about 16% in hospitalized adult patients. The clinical course is highly variable, with a few patients developing severe disease with bleeding, adult respiratory distress syndrome, encephalopathy and hypovolemic shock. We studied 70 patients admitted with suspected Lassa fever to a hospital in Sierra Leone, West Africa. Fourteen patients classified as having severe Lassa fever on the basis of serum aspartate amino transferase (AST) > 150 IU/L or viremia of > 103.6 tissue culture infective dose (TCID) 50/ml were found to have statistically significantly depressed lymphocyte counts when compared with patients with mild Lassa fever (AST <150 IU/L or viremia, <103.6TCID50/ml), (P <0.0001) and with febrile control patients, in whom Lassa infection had been excluded by laboratory criteria (P<0.0008). Maximum depression occurred a mean of 10.9 days post onset. Patients with severe Lassa fever also had moderate thrombocytopenia, which was statistically significant when compared with febrile control patients (P<0.0003) and this occurred a mean of 10.8 days postonset. The most significant changes were in platelet function, which was markedly depressed in patients with severe Lassa fever (P<0.0035 in response to ADP and P=0.0081 for collagen) when compared with patients with mild Lassa fever, and when compared with febrile controls, (P=0.0013 for ADP and P<0.00001 for collagen). This abnormality was usually maximal on admission to hospital, and probably is an early event, preceding hospitalization in these patients. Characteristically it is present even when circulating platelet numbers remain above 100 × 109/L. Though this defect was significantly associated with Lassa fever in the patients studied, platelet dysfunction was also observed in a small number of patients with laboratory confirmed malaria within the febrile control group of patients. In contrast, prothrombin times and partial thromboplastin times in Lassa fever patients were rarely abnormal, and there were no statistically significant differences between Lassa fever patients and febrile controls in coagulation tests or in fibrinogen degradation product levels.
Inactivation of the Hutchinson strain of hepatitis non‐A, non‐B virus in intravenous immunoglobulin by β‐propiolactone
Authors: Stephan Wolfgang , Dichtelmuller Herbert , Prince Alfred M. , Brotman Betsy , Huima Tellervo
Published: March 2007

β‐propiolactone (β‐PL) treatment has been evaluated for its ability to inactivate 103.5 chimpanzee infectious doses (CID50) of the Hutchinson strain of hepatitis non‐A, non‐B virus (HNANBV). Two chimpanzees were inoculated with a β‐PL‐treated immunoglobulin solution to which this dose of the titrated virus had been added prior to β‐PL treatment. β‐PL treatment was performed in accordance with the production procedure used for a licensed intravenous immunoglobulin preparation. Neither animal developed hepatitis. When subsequently challenged with the same spiked immunoglobulin solution that had not been β‐PL treated, both animals developed clear‐cut hepatitis non‐A, non‐B. The results of this experiment demonstrate that β‐PL treatment is effective for the inactivation of hepatitis non‐A, non‐B virus in intravenous immunoglobulin.
Inhibition of human hepatitis B virus DNA polymerase and duck hepatitis B virus DNA polymerase by triphosphates of thymidine analogs and pharmacokinetic properties of the corresponding nucleosides
Authors: Tao Pei‐Zhen , Löfgren Bengt , Lake‐Bakaar Desmond , Johansson Nils Gunnar , Datema Roelf , Öberg Bo
Published: March 2007

Replication of hepadnaviruses involves a viral DNA polymerase containing both a DNA‐dependent and an RNA dependent activity. This polymerase is a potential target for chemotherapy against hepatitis B. We have used human hepatitis B virus DNA‐dependent DNA polymerase from human serum and duck hepatitis B virus DNA‐dependent DNA polymerase from duck serum as well as RNA‐dependent DNA polymerase activity from duck hepatitis B‐infected duck liver. Triphosphates of thymidine analogs have been synthesized and tested for their inhibitory activities against these enzymes with the intention both to explore differences between these enzymes and structural requirements for inhibitors.

The results showed that with the inhibitors tested, hepatitis B virus DNA‐dependent DNA polymerase was the most sensitive enzyme and the triphosphate of 5‐propenyl‐2′‐deoxyuridine was the most active inhibitor. In addition, the 5′‐triposphate of 5‐propenyl‐arabinofuranosyluracil also inhibited the hepadnavirus DNA‐dependent DNA polymerases, and was a competitive inhibitor with respect to 2′‐deoxythymidine triphosphate as showed by kinetic studies with duck hepatitis B virus DNA‐dependent DNA polymerase from serum.

Pharmacokinetic analysis showed 5‐propenyl‐2′‐deoxyuridine to be well absorbed orally, but rapidly cleared from plasma. The arabinofuranosyl analog was also well absorbed but cleared less rapidly. Hence, these results indicate the potential of 5‐propenyl‐2′‐deoxyuridine and 5‐propenyl‐arabinofuransyluracil for chemotherapy of hepatitis B.
Effect of natural human interferon‐beta on the replication of human cytomegalovirus
Authors: Nakamura Kazuo , Eizuru Yoshito , Minamishima Yoichi
Published: March 2007

The antiviral effect of natural human interferon‐beta (HuIFN‐β) against human cytomegalovirus (CMV) was evaluated in human embryonic lung fibroblasts (HEL). Natural HuIFN‐β, like other HuIFNs, inhibited the replication of CMV. Pretreatment of the cells with natural HuIFN‐β inhibited the appearance of immediate‐early antigen (IEA) or pre‐early nuclear antigen (PENA) as well as the production of infectious CMV. After a single treatment with natural HuIFN‐β, intracellular 2′, 5′‐oligoadenylate (2‐5A) synthetase activity was induced and maintained at a high level for several days. The anti‐CMV effect of natural HuIFN‐β correlated with the intracellular 2‐5A synthetase activity.
Viruslike particles in liver in sporadic non‐A, non‐B fulminant hepatitis
Authors: Fagan Elizabeth A. , Ellis David S. , Tovey George M. , Portmann Bernard , Williams Roger , Zuckerman Arie J.
Published: March 2007

In a patient who followed the typical clinical course of fulminant hepatitis attributable to “sporadic” non‐A, non‐B (NANB) hepatitis and who finally received treatment by orthotopic liver grafting, three, apparently separate, viruslike agents (26, 45, and 80 nm) and cytoplasmic, reticular tubular structures (CTS) were identified in collapsed and regenerating areas of liver using electron microscopy. The 80‐nm particles present within vacuoles, together with the finding of intranuclear rods in association with the smaller particles (26 nm), are similar to those found in the nuclei of cells infected with several different arboviruses. The third type of particle, existing as 45‐nm spheres and rods, is similar in morphology only to some form of polyoma virus, which, hitherto, has not been reported as affecting the liver. Unlike typical polyoma virus, replication of the virus “cores” (25–26 nm) was extranuclear and appeared to be occurring in vacuoles. Although analysis for serological markers against a representative panel for arboviruses, flaviviruses, phleboviruses, arenavirus, and nairovirus was negative, an insect vector was implicated in the clinical history.
T lymphocyte subsets and viral infections in sardinian parenteral drug abusers: Relationship to HIV infection
Authors: Farci Patrizia , Novick David M. , Lai M. Eliana , Orgiana Giuseppina , De Gioannis Daniela , Coiana Alessandra , Strazzera Antonello , Marongiu Francesco , Balestrieri Angelo
Published: March 2007

To investigate whether the human immunodeficiency virus (HIV) infection or the abuse of narcotic drugs or other viral infections may be responsible for immunologic abnormalities in parenteral drug abusers, sera from 168 consecutive individual patients were collected from 1985 to 1986. The sera were tested for antibody to HIV (anti‐HIV), and the clinical, immunologic, and serologic characteristics of 83 seropositive and 53 seronegative parenteral drug abusers were compared. The presence of anti‐HIV was significantly associated with a decreased number of T helper lymphocytes (P < 0.001), a reduced T helper/suppressor ratio (P < 0.001), and generalized lymphadenopathy (P < 0.001). Of the 83 seropositive patients, 63 (76%) had generalized lymphadenopathy and 16 (18%) had AIDS‐related complex. No patient had AIDS. Parenteral drug abusers with AIDS‐related complex had significant reductions in the number of T helper cells (P < 0.01) and the T helper/suppressor ratio (P < 0.01) compared with patients with lymphadenopathy syndrome (LAS), suggesting that parenteral drug abusers with HIV infection develop a progressive immunodeficiency. IgG antibody to cytomegalovirus was found in 75% of anti‐HIV‐positive and 45% of anti‐HIV‐negative parenteral drug abusers (P < 0.01), but significant associations between anti‐HIV and markers for other viruses were not found. Our data confirm that HIV infection is the major cause of low T helper cells and reversed T helper/suppressor ratio in parenteral drug abusers.
Long‐term immune reactivity to pre‐S(2)‐antigen after acute hepatitis B infection
Authors: Heijtink Rudolf A. , de Wilde Gerrie A. , van Hattum Jan , Schalm Solko W.
Published: March 2007

We investigated sera from 39 patients, taken 1–8 years after recovery from acute hepatitis B for anti‐pre‐S(2) by Western blotting and for anti‐HBs by radioimmunoassay. Anti‐pre‐S(2) antibodies were found in 27 out of 39 sera (69%) with the highest frequency in sera with anti‐HBs > 100 IU/I (92%). However, sometimes sera with low anti‐HBs titres showed a strong response in Western blotting.

Acute hepatitis sera were also investigated from a limited number of patients (n = 14). Antipre‐S(2) antibodies were found during antigenaemia (four out of six patients) and within 3 months after the maximum of alanine amino transferase (ALAT) (seven out of ten patients).

Anti‐pre‐S(2) is an early antibody. It remains in the circulation for many years similar to but independent of anti‐HBs.
Intestinal immunity to poliovirus develops only after repeated infections in monkeys
Authors: Selvakumar R. , John T. Jacob
Published: March 2007

To establish gut immunity in monkeys to poliovirus type 1, we fed four juvenile bonnet monkeys (Macaca radiata) with 100 median infectious doses of the Mahoney strain of virus. The duration of viral shedding in the throat and faeces and the titre of virus in faeces were measured. Eighteen days after the last monkey stopped shedding virus, they were inoculated once again with the same amount of virus. All monkeys got re‐infected the duration and titres of viral shedding were very similar to those after the first inoculation. This was interpreted to mean a lack of effective gut immunity. After a third inoculation the re‐infection was of very short duration, and viral titres were one log10 less, indicating a high degree of gut immunity. These results suggest that one infection by poliovirus does not induce gut immunity; at least two infections are necessary to induce it. Even after two consecutive infections, immunity was not sufficient to prevent re‐infection.