The etiologic agents of varicella and herpes zoster; serologic studies with the viruses as propagated in vitro

The preparation of antigenic materials capable of specific fixation of complement in the presence of convalescent phase sera from patients with varicella and herpes zoster is described. Satisfactory antigens were obtained by the repetitive harvest and subsequent concentration of the pooled nutrient fluids from bottle cultures of human embryonic skin-muscle tissue or of monkey kidney tissue infected with varicella or herpes zoster viruses. Specific fixation of complement was also demonstrated with antigens prepared from extracts of the infected cell sheets harvested from bottle cultures. In individuals with varicella, complement-fixing antibody usually appeared in the serum 4 or 5 days after the development of the exanthem and further significant increases in titer were characteristically observed during the 2nd week of illness. The complement-fixing antibody response in herpes zoster tended to follow the same pattern as in varicella, with the exception that in sera from some individuals relatively high titers were present in the acute phase specimen. Complement-fixing antigens prepared from varicella strains or from a zoster strain reacted to essentially the same degree with convalescent sera from the homologous and the heterologous clinical entities. The varicella-zoster antigens did not fix complement in the presence of paired sera obtained from a limited number of individuals with primary infections due to herpes simplex virus or from individuals with generalized vaccinia infection. Specific inhibition in vitro of the focal cytopathic process produced by the varicella-zoster viruses was demonstrated. This was accomplished by the incorporation of the sera under test as constituents of nutrient media of the cultures, either prior to or at the time of their inoculation with virus. The neutralization of focal cytopathogenicity thus obtained was relative in degree and never absolute; it was therefore assayed by repetitive counts of the number of focal lesions per culture in the various test groups. Inhibition of varicella-zoster viral cytopathogenicity occurred in the presence of convalescent serum from either clinical entity. The results of the immunologic studies with the viruses of herpes zoster and varicella as propagated in vitro are considered as providing further evidence in support of the concept of the close relationship and probable identity of the two agents.     

Ohio strains of a virus pathogenic for infant mice,Coxsackie group; simultaneous occurrence with poliomyelitis virus in patients with summer grippe

Further evidence for the widespread occurrence of Coxsackie or C virus is presented in this paper. This virus is characterized by paralysis and myositis produced in infant mice. An epidemic of mild illnesses diagnosed as "non-paralytic poliomyelitis" and as "summer grippe" occurred during the summer of 1947 in Akron and Cincinnati, Ohio. From the pooled feces of such patients both poliomyelitis virus and C virus were obtained. From the samples of single patients, 3 immunologically related strains of C virus were isolated. One patient from whom virus was isolated had an illness which was diagnosed as non-paralytic poliomyelitis (with pleocytosis). Although poliomyelitis virus could not be isolated from this patient, previous tests (5) from similar non-paralytic patients in the same area revealed that 9 of 23 were infected with poliomyelitis virus. C virus could not be recovered from the stools of 3 of these poliomyelitis virus-infected patients. Four patients with an illness diagnosed as "summer grippe" were tested. Two harbored poliomyelitis virus of low virulence (4) as well as C virus, and two harbored poliomyelitis virus without any evidence of infection with C virus, either by virus isolation or by serological tests. The patients from whom C virus was isolated developed complement-fixing antibodies 4 weeks after onset. Neutralizing antibodies appeared within the first 5 days of disease (before complement-fixing antibodies) and increased in titer during the next 3 to 4 weeks. The patients from whom C virus could not be recovered failed to develop either neutralizing or complement-fixing antibodies. Other patients in the area were infected with C virus as indicated by their serological response to the agent.     

急性心肌梗死与柯萨奇B组病毒感染关系的研究

目的　探讨柯萨奇B组病毒感染与急性心肌梗死 (AMI)的发病关系。方法　应用SPA吸收IgG结合间接ELISA法检测AMI患者血清中柯萨奇B组病毒特异性IgM抗体及中和抗体。结果　 4 8例AMI患者血清特异性IgM抗体阳性率为 75 % ,血清中和抗体阳性率为 85 4 % ,与正常对照组相比差异非常显著。双份血清试验 ,恢复期血清抗体效价高于初期血清抗体效价 4倍以上。结论　AMI发病与柯萨奇B组病毒感染有关。     

Quantitative determination of antibody to capsular polysaccharide in infection with type III strains of group B Streptococcus.

The development of antibody in response to invasive infection with type III strains of group B Streptococcus was studied in sera from 31 infants and 4 adults by means of a quantitative radioactive antigen-binding assay. Low concentrations of antibody were consistently found in the acute sera of patients who developed clinical illness. Although adults with puerperal sepsis and infants with bone or joint infection uniformly demonstrated significant rises in serum antibody concentration after recovery, much lower levels of antibody were detected in convalescent sera from infants recovering from meningitis or sepsis. The median antibody concentration in sera from 43 parturients with type III strains of group B Streptococcus isolated from vaginal cultures whose neonates failed to develop symptomatic disease was significantly greater than that in sera from 29 mothers of infants with invasive, type III, group B streptococcal infection. Study of paired maternal and cord sera demonstrated a significant correlation between the antibody concentration in a mother's serum and that in her neonate.     

The antibody response following hepatitis A infection.

A specific IgM response to hepatitis A virus was detected in sera from patients suffering acute hepatitis A infection. The presence of virus-specific IgM in 19S components of acute and early convalescent phase sera was detected by immune electron microscopy and solid-phase radioimmunoassay. The presence of virus-specific IgM in whole serum specimens was demonstrated by indirect immunoferritin labeling. Following acute infection, however, the major immunoglobulin response appears to be IgG, since titers of specific 7S and whole serum antibody were very similar.     

NEUTRALIZING ANTIBODIES IN ABORTIVE POLIOMYELITIS

The neutralizing antibody content for poliomyelitis virus has been tested with both a human and a passage strain of the virus in serial samples of sera from five mild cases of abortive poliomyelitis, and an increase in this antibody content has been demonstrated in convalescent samples obtained within 4 weeks of the acute illness.     

Factors associated with high antibody titer following coronavirus disease among 581 convalescent plasma donors: A single-center cross-sectional study in Japan

IntroductionThe ability to predict which patients with a history of coronavirus disease (COVID-19) will exhibit a high antibody titer is necessary for more efficient screening of potential convalescent plasma donors. We aimed to identify factors associated with a high immunoglobulin G (IgG) titer in Japanese convalescent plasma donors after COVID-19.MethodsThis cross-sectional study included volunteers undergoing screening for convalescent plasma donation after COVID-19. Serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein IgG antibodies were measured using a high-sensitivity chemiluminescence enzyme immunoassay.ResultsIgG antibodies were measured in 581 patients, 534 of whom had full information of selected independent variables. Multiple linear regression analysis revealed that increasing age (1.037 [1,025, 1.048]), days from symptom onset to sampling (0.997 [0.995, 0.998]), fever (1.664 [1.226, 2.259]), systemic corticosteroid use during SARS-CoV-2 infection (2.382 [1.576, 3.601]), and blood type AB (1.478 [1.032, 2.117]) predict antibody titer.ConclusionOlder participants, those who experienced fever during infection, those treated with systemic corticosteroids during infection, those from whom samples were obtained earlier after symptom onset, and those with blood type AB are the best candidates for convalescent plasma donation. Therefore, these factors should be incorporated into the screening criteria for convalescent plasma donation after SARS-CoV-2 infection.     

Factors associated with anti-SARS-CoV-2 IgG antibody production in patients convalescing from COVID-19

IntroductionAmong patients with coronavirus disease 2019 (COVID-19), the factors that affect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production remain unclear. This study aimed to identify such factors among patients convalescing from COVID-19.MethodsThis study comprised patients who had been diagnosed with COVID-19 between January 1 and June 30, 2020 and gave consent for anti-SARS-CoV-2 spike protein antibody measurement using enzyme-linked immunosorbent assay during their acute and/or convalescent phases. Factors related to elevated antibody titers and the relationship between the days from disease onset and the development of antibody titers were assessed.ResultsA total of 84 participants enrolled in the study. Nineteen participants had antibody titers measured during the convalescent phase only, and 65 participants had antibody titers measured during the acute and convalescent phases. The antibody titers peaked in weeks 5 and 6. The stepwise multivariate log-normal analysis revealed that male sex (P = 0.04), diabetes mellitus (P = 0.03), and high C-reactive protein levels during the disease course (P < 0.001) were associated with elevated IgG antibodies. Glucocorticoid use was not associated with antibody titers.ConclusionThe study found that high values of maximum CRP levels during the acute phase, male sex, and diabetes mellitus were associated with elevated antibody titers. Antibody titers tended to be highest in the first 5 or 6 weeks after the onset of symptoms.     

SARS患者康复期肺功能的变化

目的了解严重急性呼吸综合征(SARS)患者康复期肺功能的特征性及其变化规律。方法对26例SARS患者出院后每隔3个月进行1次肺功能检查，分析康复期肺功能各指标的意义。结果SARS患者发病后第3～6个月肺功能主要表现为限制性通气功能障碍和弥散功能障碍。不同时间段(3～6个月、6～9个月、9～12个月、12～15个月、15～17个月)的用力肺活量(FVC)、1秒用力呼气容积(FEV1.0)、功能残气量(FRC)和残气容积(RV)差异均无显著性，但随康复时间的延长而逐渐增加；同时FEV1.0／FVC变化不大；而肺总量(TLC)和肺一氧化碳弥散量(DLCO)在不同时间段均有不同程度的好转。结论SARS患者发病后肺功能的损害主要表现为限制性通气功能障碍和弥散功能障碍，但随康复时间的延长两者均逐渐恢复。     

Limitations of polymerase chain reaction testing for diagnosing acute Epstein-Barr virus infections

Clinicians use molecular tests to detect Herpesviridae from blood without fully appreciating limitations of testing. Studies are needed to enhance our understanding of the impact of Herpesviridae latency on molecular testing. We retrospectively performed quantitative Epstein-Barr virus (EBV) on sera from patients between the ages of 1 and 30 who demonstrated serologic evidence of acute EBV (n = 50) or remote EBV (n = 50) infection. Epstein-Barr virus DNA was detected in 70% of acutely infected and 4% of remotely infected patients. Sera from acutely infected patients had higher EBV copy number than convalescent sera. Our results suggest that serology should be performed as the initial diagnostic test for acute EBV. The role for polymerase chain reaction in immunocompromised patients with impaired antibody responses or as a 2nd-line diagnostic test when serologic results are equivocal deserves further study.     

Prevalence of Positive Serology for Acute Chlamydia pneumoniae Infection in Emergency Department Patients with Persistent Cough

Objective : To determine the prevalence of acute Chlamydia pneumoniae infection in ED patients presenting with a persistent cough.
Methods : This was a case series consisting of a convenience sample of 65 patients ≥18 years of age who presented with a chief complaint of a cough lasting ≥2 weeks. Patients were treated in the ED of an urban university hospital. Patients with immunosuppression, lung disease, pneumonia, or a cough lasting ≥3 months were excluded. Acute and convalescent sera were assayed for antibody to C. pneumoniae . Subjects with C. pneumoniae antibody titers showing a fourfold rise in either immunoglobin M (IgM) or immunoglobin G (IgG) antibody, an IgM titer of ≥16, or an IgG titer of≥512 were considered to have evidence of acute C. pneumoniae infection.
Results : Thirteen (20%; 95% CI, 11% to 32%) of the 65 subjects had serologic evidence of acute C. pneumoniae infection. Except for an increased rate of fever, clinical signs and symptoms and laboratory studies did not differentiate those who had C. pneumoniae from those who did not have the disease. Patients diagnosed as having Bordetella pertussis or Mycoplasma pneumoniae infection did not have serologic evidence of concurrent C. pneumoniae infection.
Conclusions : C. pneumoniae infection appears to be associated with a persistent cough in ED patients. Clinicians should consider this organism when evaluating these patients. It is unclear whether antibiotic therapy is indicated for these patients. If antibiotics are used, a tetracycline or macrolide antibiotic would be most appropriate.     

STUDIES ON THE SOMATIC C POLYSACCHARIDE OF PNEUMOCOCCUS : II. THE PRECIPITATION REACTION IN ANIMALS WITH EXPERIMENTALLY INDUCED PNEUMOCOCCIC INFECTION

The capacity of the serum of rabbits following intradermal pneumococcus infections to precipitate in the presence of pneumococcus C polysaccharide has been studied during the resultant periods of active infection and during recovery. In rabbits infected with Type I, III, or VIII pneumococci, large hemorrhagic lesions are produced which frequently bring about death of the animals after a febrile illness of 3 to 4 days. Repeated precipitation tests with the sera of these animals have been uniformly and consistently negative, not only during the acute illness but in the recovery period as well. On the other hand, the sera of monkeys of the Macacus cynomolgos species actively ill with experimental Type III pneumonia have been shown to react in precipitation tests with the C substance. The serum reaction appears within the first 24 hours after infection, remains positive in high titer for 2 to 3 days during the acute illness, and disappears with the onset of recovery. The precipitation reaction with C also occurs with the sera of monkeys following intradermal and intraperitoneal infection with pneumococci. The results of precipitation tests of the serum of monkeys during experimental pneumonia are similar to those obtained with the sera of patients suffering from pneumococcus lobar pneumonia. From the results of these studies it would appear improbable that the demonstration of the serum precipitation phenomenon with C polysaccharide in monkeys, and possibly also in man, is conditioned by previous exposure to pneumococcus antigen.     

PERSISTENCE OF STREPTOCOCCAL GROUP A ANTIBODY IN PATIENTS WITH RHEUMATIC VALVULAR DISEASE

Antibody levels to streptococcal Group A and A-variant carbohydrates were determined using a radioactive immune precipitation technique on patients with rheumatic fever, with and without valvular disease, on patients with post-streptococcal acute glomerulonephritis, and on age-matched controls. During the acute phase of the above illness, the means of the antibody levels to both carbohydrate antigens were equally elevated and were significantly higher than the normal controls. When Group A antibody levels were determined on sera obtained at intervals of 5–12 months and 1–5 yr after the acute illness) it was found that the antibody levels declined within the normal range at the 5–12 month interval in patients with glomerulonephritis as well as in patients with rheumatic fever in whom no valvular involvement had complicated the disease, i.e., patients with pure Sydenham's chorea. However, in patients with rheumatic valvulitis, who had been on penicillin prophylaxis after the last acute episode, the A antibody level showed little decline from the level obtained during the acute illness. The elevated antibody level in patients with rheumatic valvulitis, including patients with Sydenham's chorea with valvulitis, persisted for periods of at least 1 yr and up to 20 yr after the last acute attack. The pattern of the decline of the antibody levels to the A-variant carbohydrate as well as of the antibody titers to the other streptococcal antigens tested, ASO and anti-DNase B, was similar in all patients studied regardless of the presence of valvular disease. These findings suggest that prolonged persistence of the Group A antibody is a phenomenon peculiar to patients with rheumatic valvular disease. Whether this persistence is involved in the pathogenesis or is an outcome of the valvular disease remains to be determined.     

An evaluation of measles serodiagnosis during an outbreak in a vaccinated community

During an epidemic of measles in a vaccinated community, five serodiagnostic tests were performed on 67 persons on whom clinical and epidemiological data were available. The test found most suitable for a rapid diagnosis of measles infection was an Enzyme Linked Immuno Sorbent Assay for the detection of specific IgM antibodies. Only one false negative IgM was recorded. In a group of 45 persons who fulfilled the clinical definition of measles, specific IgM antibodies were detected in the acute phase serum of only 30 (66.6%), of whom 17 were vaccinated. When the convalescent sera were tested, specific IgM antibodies were detected in 25 of the 28 (89.2%) vaccinated, and in 17 of the 17 (100%) non vaccinated clinical cases. A convalescent blood should be tested in persons with a rash illness and no IgM antibodies in the acute phase serum. There were individual variations in the time of appearance of IgM. On the day of onset of rash, IgM antibodies were detected in 7 of the 12 (58.3%). A history of prior vaccination is not always associated with immunity nor with the presence of specific antibodies.     

PERIOD OF INFECTIVITY OF PATIENTS WITH HOMOLOGOUS SERUM JAUNDICE AND ROUTES OF INFECTION IN THIS DISEASE

1. Pooled specimens of serum obtained from 3 human volunteers three-fourths through their respective 56, 66, and 70 day incubation periods of homologous serum jaundice produced the disease in 1 out of 4 human volunteers following parenteral inoculation. 2. Serum specimens obtained from these same 3 patients during the acute, pre-icteric phase of their homologous serum jaundice produced the disease in 3 out of 4 human volunteers following parenteral inoculation. 3. These same sera, proven to be infectious by parenteral inoculation, failed to produce disease when ingested by 10 other human volunteers. 4. Pooled specimens of serum obtained in the convalescent phase (28 to 32 days after onset) of these 3 patients failed to produce apparent infection when inoculated parenterally into 5 human volunteers. 5. Pooled specimens of feces of 3 patients obtained in the acute phase of homologous serum jaundice, when virus was proven to be in the serum, were not demonstrably infectious when fed to 6 volunteers. 6. These findings are slightly different from those encountered in a similar study with infectious material from cases of infectious hepatitis.     

Studies on primary atypical pneumonia. II. Observations concerning the development and immunological characteristics of antibody in patients

By using the indirect method of fluorescent staining to study the antibody response in patients with primary atypical pneumonai associated with the development of cold agglutinin, it was found that the PAP antibody developed during the 2nd and 3rd week of the illness, and persisted for over a year, and is not related to the cold and streptococcus MG agglutinins. The development of the PAP fluorescent staining antibody paralleled the neutralizing antibody for the PAP virus as tested in cotton rats. The sensitivity of this specific serological test was indicated by the observation that 67 to 92 per cent of the patients in several outbreaks of PAP showed a rise of antibody titer during convalescence. Absorption of the sera with various tissue powders did not affect the PAP antibody detected by this method.     

Homotypic complement-fixing antibody in monkeys infected with type 2 poliomyelitis virus by the oral route

CF tests with Type 2 poliomyelitis antigen (MEF1) were performed on the pre- and postinfection sera of 20 cynomolgus monkeys which developed paralytic, non-paralytic, or inapparent infection following oral administration of a Type 2 strain of virus (Y-SK). All the monkeys developed neutralizing antibody, and 17 developed CF antibody in an original serum dilution titer of 1:4 or greater. The 3 monkeys which did not develop this level of CF antibody were in a group of 7 which died within 8 days after onset of paralysis. The CF titers were as high at 2 to 6 days after onset of paralysis in the other 4 moribund or dead monkeys as in the surviving animals tested 4 weeks after the first dose of virus and the CF titers were of the same order of magnitude in the groups with paralytic, non-paralytic, or inapparent infection. The Type 2 poliomyelitis CF titers developed in monkeys as a result of infection with homotypic virus were not greater than those found in human beings infected with heterotypic Type 1 poliomyelitis strains.     

Antibody-Associated Lymphotoxin in Acute Infection

Five pediatric patients who were known to be previously healthy acutely developed lymphopenia during various viral or mycoplasma infections. In one case, fatal generalized varicella occurred and in another, severe toxic epidermal necrolysis ensued.To further investigate this phenomenon, a study was done to determine the incidence of and elucidate the pathogenesis of lymphopenia occurring during the acute phase of viral or mycoplasma infections. Acute and convalescent sera from patients with viral or mycoplasma infection and children immunized with live measles virus were screened for lymphocytotoxic activity against normal lymphocytes by the microcytotoxicity method of Terasaki and McClelland (1). Sera with lymphocytotoxic activity were found in 15 of 48 cases of viral infections, 4 of 22 mycoplasma infections, and 1 of 11 measles virus immunized persons. All those who had sera which were cytotoxic to lymphocytes in vitro had lymphopenia. The lymphocytotoxic activity resided in 19S fractions in 8 of 11 positive sera while the remaining 3 had activity both in 19S and 7S fractions and could be completely removed by absorption with antilight chain antiserum. The cytotoxic activities were all complement-dependent and were greater at 37 degrees C than at 4 degrees C.The significance of acute acquired immunologic deficiency due to the development of antibody-associated lymphotoxin (AbAL) during acute infections is discussed and five cases having more severe clinical manifestations are presented (Appendix).     

Application of immune adherence hemagglutination test in the screening of blood donors carrying a high titer antibody to varicella-zoster virus

The immune adherence hemagglutination (IAHA) test was compared with the complement fixation (CF) test and fluorescent antibody (FA) test to measure the antibody titer to varicella-zoster virus (VZV) in 70 sera of convalescents 2 to 8 weeks after herpes zoster onset. The IAHA titer correlated with the FA titer, but not with the CF titer which was lower than the IAHA and FA titers. Then, the IAHA test was used for screening of blood donors with a high titer (higher than 64 units) of antibody to VZV from 2,592 blood donors. About 14% of the sera from the donors aged 16 to 19 years had an antibody titer higher than 64 units, about 10% of sera from the donors aged 20 to 49 years, and 5.6% of sera from the donors older than 50 years. An average positive rate was about 9%, indicating that an enough VZV immune plasma with a high titer of antibody might be obtained from blood donors.     

面神经炎与抗水痘-带状疱疹病毒抗体的相关性探讨

目的　通过比较面神经炎患者与正常对照之间的抗水痘 带状疱疹病毒抗体滴度的差异以及面神经炎患者在不同疾病阶段的抗水痘 带状疱疹病毒抗体滴度变化 ,探讨抗水痘 带状疱疹病毒抗体与面神经炎之间的关联。方法　用酶标记葡萄球菌A蛋白 (SPA)染色法对 11例面神经炎患者及 2 6例正常人血清中抗水痘 带状疱疹病毒 (VZV)抗体进行检测 ,还对其中 6名患者进行了发病早期及 2周后的血清抗VZV抗体检测。结果　面神经炎患者组的抗VZV抗体滴度显著高于对照组 (P <0 .0 5 ) ;在 6例患者的不同疾病阶段测得的抗体滴度中 ,3例患者在发病 2周后抗体滴度比发病初期增加 4倍以上 ,1例增加 2倍 ,2例无改变。结论　抗VZV抗体滴度与面神经炎的发病相关 ,提示VZV感染可能是面神经炎的致病因素之一。