Serological diagnosis of infection with human herpesvirus type 6.

OBJECTIVE--To identify clinical consequences of acute human herpesvirus type 6 infection by hypothesising that the virus will induce similar clinical syndromes to cytomegalovirus. DESIGN--Examination of consecutive serum samples from patients with illnesses compatible with acute cytomegalovirus infection or exanthem subitum by indirect immunofluorescence for the presence of antibodies to human herpesvirus type 6. An IgG absorption step was included to avoid false positive and negative results for IgM. The criterion standard for diagnosis of human herpesvirus type 6 infection was the presence of IgM human herpesvirus type 6 antibody (titre greater than 20) and a rising titre of IgG human herpesvirus type 6 antibody without serological evidence of alternative infection. SETTING--Routine viral diagnostic and reference laboratory in the largest teaching hospital in Sydney. PATIENTS--341 Consecutive serum samples were analysed from patients with hepatitis (147 samples); infectious mononucleosis-like illness (106); screens for toxoplasma, other viruses, rubella, cytomegalovirus, and herpesvirus (38); fever in an immunocompromised patient (eight); unusual neurological (nine) or haematological syndromes (14); splenomegaly (six); and rash in a child (13). RESULTS--Three cases of acute human herpesvirus type 6 infection were identified: in one patient aged 65 with a previous diagnosis of acute non-A non-B hepatitis, one aged 25 with a glandular fever-like illness, and one aged 6 with a glandular fever-like illness. All three illnesses resolved completely. 15 Further serum samples were positive for human herpesvirus type 6 antibody but were also diagnostic for acute infection with other viruses (cytomegalovirus (nine), Epstein-Barr virus (three), and HIV (one] or had a titre of IgM human herpesvirus type 6 antibody less than 20 (two). CONCLUSIONS--Acute human herpesvirus type 6 infection in immunocompetent patients may result in a mononucleosis-like illness or an acute but self limiting hepatitis.     

Association of cytomegalovirus with infantile hepatitis

Infantile hepatitis is occasionally seen in apparently healthy children. In most cases, the etiology of the infection is uncertain. However, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), human herpesvirus-7 (HHV-7), human parvovirus B19, and TT virus (TTV) are considered to be associated with hepatitis in children. The objective of this study was to investigate the correlations between these viruses and infantile hepatitis. Twenty-six children from 1 to 24 months old (median age, 7 months) who had liver dysfunction of unknown etiology were enrolled in this study. Plasma samples were examined by a real-time PCR assay for CMV, EBV, HHV-6, HHV-7, parvovirus B19, and TTV DNA. The DNA of CMV was detected in the plasma of four patients (15.4%) and was detected significantly more often in the patient group than in the control group. The CMV-infected patients were 1 to 3 months old, which was significantly younger than the remaining patients. The serological findings did not always correlate with the results of the real-time PCR assay. The DNA of TTV was detected in four patients (15.4%), while human parvovirus B19 DNA was detected in three (11.5%). However, the detection frequencies of these viral DNAs were not significantly different from those in the control groups, and some of these patients had co-infections. These results indicate that CMV might be one of the major pathogens responsible for infantile hepatitis; however, serological tests have limited utility for the diagnosis of CMV infection in young children.     

Serosurveillance of Vaccine Preventable Diseases and Hepatitis C in Healthcare Workers from Lao PDR

Background and Aims

Healthcare workers (HCW) have an increased risk of exposure to infectious diseases and are a potential source of infections for their patients. The Lao People’s Democratic Republic (Lao PDR) has no national policy regarding HCW vaccinations and routine vaccination coverage is low within the general population. This cross-sectional serostudy determines the level of exposure and risk of infection in Lao HCW against 6 vaccine preventable diseases and hepatitis C.

Methods

1128 HCW were recruited from 3 central, 2 provincial and 8 district hospitals. Sera were tested by ELISA for the presence of antibodies and antigens to hepatitis B, hepatitis C, measles, rubella, varicella zoster, tetanus and diphtheria.

Results

Only 53.1% of the HCW had protective anti-hepatitis B surface antigen antibodies (anti-HBs) with 48.8% having anti-hepatitis B core antibodies (anti-HBc), indicating previous exposure and 8.0% were hepatitis B surface antigen carriers. 3.9% were hepatitis C seropositive. Measles and rubella antibodies were detected in 95.4% and 86.2% of the HCW, with 11.9% of females being unprotected against rubella. Antibodies against varicella zoster, tetanus and diphtheria were detected in 95%, 78.8% and 55.3%, respectively. Seroprevalence varied according to age, gender and number of children.

Conclusion

An unacceptably high proportion of Lao HCW remain susceptible to infection with hepatitis B, diphtheria, tetanus and rubella. Furthermore, a high number of healthcare workers are chronically infected with hepatitis B and C viruses. These data emphasize the need for a robust HCW vaccination policy in addition to increased awareness within this subpopulation.     

Hereditary blood factors and infectious diseases in children in the 1st 7 years of life

Infectious morbidity in respect to 23 nosological forms was studied in 958 children with known blood groups and Rh factors during the first 7 years of their life. The absence of statistically significant differences in morbidity rates in children with different age groups was revealed in respect to 16 nosological forms. Significant differences in morbidity rates in children with different blood groups were revealed in respect to parotitis, rubella, scarlet fever, E. coli infections, bronchitis and pneumonia; similar differences linked with Rh factor were observed only in cases of measles, rubella and tonsillitis.     

Hepatitis non-A,non-B.

Evidence for the existence of hepatitis non-A, non-B includes epidemiologic data and results of transmission studies indicating the presence of hepatitis that could not be explained by known causative agents. The diagnosis is suggested in patients who have multiple episodes of acute hepatitis or who contract hepatitis after transfusion, hemodialysis or drug abuse. Sporadic cases are common. Three such cases are described to illustrate that the disease is clinically indistinguishable from hepatitis A or B. The diagnosis is based on the absence of serologic markers of hepatitis A and B and of infection by Epstein-Barr virus and cytomegalovirus, or on serologic evidence of previous infection with hepatitis A and B.     

A study of sister-chromatid exchange in peripheral lymphocytes of hepatitis B patients with HBsAg positive and their children

Previous studies of sister-chromatid exchange (SCE) in patients with hepatitis B have been reported. But as far as we know, no such work has been done in children born to parents with hepatitis B, either one or both of whom are infected. In the present study, frequencies of SCE in the peripheral lymphocytes of 30 hepatitis B parents with hepatitis B surface antigen (HBsAg) positive and 40 of their children were observed. SCE frequencies of 20 normal adults and 3 normal children were analysed for comparison with the patients and their children. The results obtained from all of the samples were as follows: The hepatitis B patients with HBsAg positive had a significantly higher SCE frequency than the normal adults (P less than 0.01); the children born after their parents contracted hepatitis B had a significantly higher SCE frequency than normal children (P less than 0.01); there was no significant difference in SCE (P greater than 0.05) between children born after their parents contracted hepatitis B, children born after their mothers acquired it and children born after their fathers acquired it. The above results indicate that hepatitis B patients with HBsAg positive and their children born after they contracted hepatitis B had significantly higher frequencies of SCE; these data might throw new light on the study of genetic factors acting on the mechanism of hepatitis B.     

Chronic viral diseases.

Until 20 years ago the only chronic viral diseases known were those considered to be confined to the nervous system. As a result of recent advances in epidemiology, molecular biology and immunology, new viral diseases have been recognized and their clinical features and pathogenesis elucidated. Chronic disease may result from infection with the hepatitis B and D viruses and whatever agent or agents cause hepatitis non-A, non-B, the herpesviruses, Epstein-Barr virus, cytomegalovirus and human T-lymphotropic virus type III. These diseases have common features, including long-term or even lifetime asymptomatic carriage, viremia, with virus free in the plasma or attached to circulating mononuclear cells, presence of virus in body secretions, irreversible tissue injury in target organs and oncogenic potential. New information on these diseases is reviewed. Other chronic diseases for which the cause is currently unknown may eventually prove to be due to viral infection. In addition, vaccines may be developed for prophylaxis of some chronic viral diseases and associated malignant diseases.     

Frequency of finding hepatitis B viral markers in young children born of mothers carrying the HBs-antigen

The present communication deals with the results of investigations on the frequency of HBsAg-carriership among expectant mothers in Fergana (the Uzbek SSR) and on the risk for their children to be infected with hepatitis B virus. To detect the markers of hepatitis B virus, the passive hemagglutination test, the enzyme immunoassay, and the radioimmunoassay were used. The incidence rate of HBsAg-carriership among expectant mothers was rather high (5.1 +/- 0.52%) in comparison with the control group (3.5 +/- 0.70%). The detection of HBsAg in children 3 months after their birth, i.e. at the term corresponding to the possible incubation period of hepatitis B, suggested that the children were infected at birth. As noted in the course of this investigation, the risk for a newborn to be infected was directly related to the titer of HBsAg, as well as to the presence of HBeAg, in the blood of the carrier mother. A high detection rate of HBsAg was registered among children born to HBsAg-carrier mothers, which makes it possible to consider these children as a high risk group with respect to hepatitis B virus infection and necessitates the development of the system of antiepidemic and prophylactic measures for preventing newborns to be infected with hepatitis B.     

Prospects for new viral vaccines

Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.     

Failure to demonstrate concomitant antibody changes to viral antigens other than Epstein-Barr virus (EBV) during or after infectious mononucleosis

A search for antibody rises to viral antigens other than to Epstein-Barr virus, the causative agent, has been carried out in serial serum samples from 82 patients with infectious mononucleosis (IM). Fourfold or greater rises in titer rarely occurred and did did not cluster in time. No rises occurred to cytomegalovirus, only 1.2 percent to herpes simplex virus, and 8.5 percent to varicella zoster virus. Rises to measles antibody were found in 7.5 percent of patients and to rubella in 10.4 percent; these may represent natural infections or immunizations. A few patients also showed rises to respiratory viruses but there was no apparent connection to IM.     

Longitudinal analysis of three intrathecally produced immunoglobulin subpopulations in an MS patient

Four murine anti-idiotypic (a-Id) hybridoma antibodies were produced against immunoglobulins (Ig) present in the cerebrospinal fluid (CSF) obtained from an MS patient 2 mo after the onset of disease. The four a-Id antibodies were shown to delineate idiotopes present on three distinct Ig subpopulations designated ID-19, ID-40, and ID-97. All three Ig subpopulations were produced in part by intrathecally localized B cells, together making up approximately 5% of the total CSF-Ig 2 mo after the onset of disease. Longitudinal analysis of the concentration of these Ig subpopulations in CSF showed that two subpopulations, ID-40 and ID-97, exhibited a regular relation to the clinical course of the disease, i.e., were decreased (ID-40) or increased (ID-97) in the first CSF sample obtained after two consecutive exacerbations. Screening of sera from 52 optic neuritis patients and 51 heterologous MS patients revealed that one MS patient's serum contained an Ig subpopulation that was idiotypically cross-reactive with ID-97. So far, screening of these Ig subpopulations for reaction with several viruses (measles, parainfluenza type 1, influenza type A, cytomegalovirus, herpes simplex virus, rubella virus, poliovirus, murine encephalomyelitis viruses, and reovirus) and myelin basic protein has failed to reveal their antigen specificities.     

Seven-year follow-up study of rubella syndrome in Ryukyu with special reference to persistence of rubella hemagglutination inhibition antibodies.

Rubella hemagglutination inhibition (HI) antibodies in 266 children with rubella syndrome born in 1965 in the Ryukyu Islands and their mothers were followed for seven years. Titers of rubella HI antibody in the mothers declined slowly, while those in the children declined rapidly up to 40 months of age. Thereafter decline of titers became extremely slow and only seven cases (three per cent) became seronegative for rubella HI antibody. Rubella HI antibody titers seemed to have no particular correlation to the severity of clinical manifestations.     

Seven-Year Follow-Up Study of Rubella Syndrome in Ryukyu with Special Reference to Persistence of Rubella Hemagglutination Inhibition Antibodies

Rubella hemagglutination inhibition (HI) antibodies in 266 children with rubella syndrome born in 1965 in the Ryukyu Islands and their mothers were followed for seven years. Titers of rubella HI antibody in the mothers declined slowly, while those in the children declined rapidly up to 40 months of age. Thereafter decline of titers became extremely slow and only seven cases (three per cent) became seronegative for rubella HI antibody. Rubella HI antibody titers seemed to have no particular correlation to the severity of clinical manifestations.     

Evaluation of the incidence of congenital rubella in GDR]

Annual number of congenital rubellas in GDR was evaluated by means of a mathematic model. Dates of inmunity rate of rubella in L. and P. districts obtained by means of haemagglutination inhibition reaction were taken into account. From these dates of a number of possible primary cases of rubella infection in wifes in the first 3 months of pregnancy as well as literary dates on mean number of monsters determined after the infection, i.e. 10--15--25% cases, were evaluated. There were obtained in relation with different mean numbers of monsters 37--56--93 cases of congenital rubellas for live born children from mothers at the age of 14 to 45 years. It results in total that the incidence of disease for live born children from mothers up to 45 years, is 0,2--0,5%, i.e. 2--5 children with congenital rubella on 10 000 live born children. Compared with literary data, it results a good correlation between proper evaluations and numbers of congenital rubella incidence quoted by other authors. In view of these evaluations, a conclusion to introduce protective rubella vaccination, is fully justified.     

Viral antibodies in infectious mononucleosis

Abstract Patients with Epstein-Barr virus (EBV) infectious mononucleosis (IM) usually develop heterophilic antibodies and some autoantibodies. Antibodies to rubella, measles, adeno-, entero-, herpes simplex, cytomegalo- and varicella-zoster viruses were titrated in sera from IM patients and matched healthy controls using the complement fixation test (CFT) and the haemagglutination inhibition test. Except for herpes simplex virus and cytomegalovirus, the IM sera had significantly higher arithmetical and geometrical mean antibody titres and showed in most cases higher antibody prevalences in the CFT. The titre rise was most pronounced for rubella and measles antibodies, between 2- and 3-fold. There were no cases of very high titres occasionally seen in IM. The IM sera had higher total IgG serum levels than the controls, 17.27 g/1 and 11.8 g/1, respectively ( P < 0.001). The present data show that in addition to previously reported high levels of some autoantibodies and of heterophilic antibodies, there is a more general increase in IgG antibodies to commonly occurring viruses. This increase is most likely due to the polyclonal activation of B-lymphocytes following the binding of EBV to the complement receptor CR2 (CD21). When due consideration is given to the possible occasional occurrence of a false positive rubella IgM test, the raised antibody-titres will most likely not interfere with routine diagnostics.     

L-deaza-5'-noraisteromycin

(+/-)-1-Deazaaristeromycin (4) has been reported to be an inactivator of S-adenosylhomocysteine (AdoHcy) hydrolase and, as a consequence, to affect S-adenosylmethionine (AdoMet) mediated macromolecular biomethylations. To extend this to our program focused on 5'-noraristeromycin derivatives as inhibitors of the same hydrolase enzyme as potential antiviral agents, both enantiomers of 1-deaza-5'-noraristeromycin (5 and 20) have been prepared. Compounds 5 and 20 were evaluated against the following viruses: vaccinia, cowpox, monkeypox, Ebola, herpes simplex type 1 and 2, human cytomegalovirus, Epstein Barr, varicella zoster, hepatitis B, hepatitis C, HIV-1 and HIV-2, adenovirus type 1, measles, Pichinde, parainfluenza type 3, influenza A (H1N1 and H3N2), influenza B, Venezuelan equine encephalitis, rhinovirus type 2, respiratory syncytial, yellow fever, and West Nile. No activity was found nor was there any cytotoxicity to the viral host cells.     

Clinical and Serological Assessment of Children Exposed in Utero to Confirmed Maternal Rubella

As a result of the work of the Public Health Laboratory Service Working Party on Rubella (1970) it was possible to examine the children of 60 susceptible women who were in contact with rubella during their pregnancy and who subsequently showed serological evidence of the infection, despite immunoglobulin prophylaxis. When the children were assessed between 8 months and 4 years 8 months of age a blood sample was also taken and tested for rubella antibodies so that a retrospective diagnosis of congenital rubella infection could be made. Only 19% of children exposed to subclinical maternal rubella showed evidence of intrauterine infection compared with 53% of those born to mothers who had clinical rubella. One of the 26 children exposed to subclinical maternal infection had a rubella defect, compared with 9 of the 34 children exposed to clinical maternal rubella.     

2003～2007年中国风疹病毒基因特征分析

本研究用Vero细胞或Vero/SLAM细胞从我国10个省(直辖市、自治区,下同)2003～2007年风疹暴发和散发病例的咽拭子标本中分离到57株风疹病毒,用RT-PCR方法扩增了57株风疹病毒E1基因1 107个核苷酸的片段,并对该PCR产物进行序列测定和分析.结果提示,在基于WHO基因定型靶序列739个核苷酸片段构建的基因亲缘关系树上,其中55株风疹病毒株属于1E基因型,相对于其他国家的1E基因型,形成一个独立分支;另外2株风疹病毒属于2B基因型.57株风疹病毒大部分核苷酸的突变为无义突变,氨基酸序列高度保守,除了2株风疹病毒在E1蛋白血凝抑制和中和位点区域第212位氨基酸由Thr变为Ser,其他病毒株均无重要抗原位点的改变;所有我国已分离到的1E基因型风疹病毒在E1蛋白第338位氨基酸共享突变位点(Leu338→Phe338),而其他基因型以及其他国家的1E基因型风疹病毒在该位点均未发生突变,提示该氨基酸(Phe338)可能是我国1E基因型风疹病毒所特有.2003～2007年在我国10个省均分离到1E基因型,而2B基因型只在2006年从四川省的越南输入病例中分离到,提示1E为绝对优势基因型,2B基因型为输入基因型.与1979～1984年和1999～2002年我国流行的风疹基因型不同,发生了基因型的更替,近年我国风疹的流行是由1E基因型为主的风疹野病毒的多个传播链引起.     

Surveillance for Seasonal Influenza Virus Prevalence in Hospitalized Children with Lower Respiratory Tract Infection in Guangzhou,China during the Post-Pandemic Era

Background

Influenza A(H1N1)pdm09, A(H3N2) and B viruses have co-circulated in the human population since the swine-origin human H1N1 pandemic in 2009. While infections of these subtypes generally cause mild illnesses, lower respiratory tract infection (LRTI) occurs in a portion of children and required hospitalization. The aim of our study was to estimate the prevalence of these three subtypes and compare the clinical manifestations in hospitalized children with LRTI in Guangzhou, China during the post-pandemic period.

Methods

Children hospitalized with LRTI from January 2010 to December 2012 were tested for influenza A/B virus infection from their throat swab specimens using real-time PCR and the clinical features of the positive cases were analyzed.

Results

Of 3637 hospitalized children, 216 (5.9%) were identified as influenza A or B positive. Infection of influenza virus peaked around March in Guangzhou each year from 2010 to 2012, and there were distinct epidemics of each subtype. Influenza A(H3N2) infection was more frequently detected than A(H1N1)pdm09 and B, overall. The mean age of children with influenza A virus (H1N1/H3N2) infection was younger than those with influenza B (34.4 months/32.5 months versus 45 months old; p<0.005). Co-infections of influenza A/ B with mycoplasma pneumoniae were found in 44/216 (20.3%) children.

Conclusions

This study contributes the understanding to the prevalence of seasonal influenza viruses in hospitalized children with LRTI in Guangzhou, China during the post pandemic period. High rate of mycoplasma pneumoniae co-infection with influenza viruses might contribute to severe disease in the hospitalized children.     

Role of heterogenized cellular antigens in cross immunity reactions in paramyxovirus infections]

Heterogenized antigens similar to the antigens of sheep and guinea pig red blood cells were revealed by indirect immunofluorescence in tissue cultures infected with parotitis virus. Participation of these antigens in cross immunofluorescence reactions observed in tissue cultures infected with various paramyxoviruses and in a suspension of erythrocytes loaded with these viruses was established. It was shown that immunization of children with parotitis virus was accompanied by a specific anamnestic reaction for heterogenized antigens. It is supposed that the corresponding antibodies can take part in cross serological tests with parainfluenza viruses.