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PubMed1997

Outbreak of gastroenteritis in military recruits associated with serotype 3 astrovirus infection.

A serotype 3 astrovirus was identified in stool samples from an outbreak of acute gastroenteritis that occurred among military recruits in France. Sixteen stools samples and eight pairs of acute- and convalescent-phase serum were collected from affected individuals. Astrovirus was detected in two stool samples by electron microscopy and in four stool samples by reverse transcriptase-polymerase chain reaction (RT-PCR). Seroconversion to the astrovirus present in one stool was detected in seven patients by using solid-phase immune electron microscopy (SPIEM) and dot blot. For three patients, the serological results were consistent with the PCR results, indicating that astrovirus was a cause of gastroenteritis in these young adults. This study describes the characterization of the serotype 3 astrovirus associated with this outbreak. The virus has a buoyant density in cesium chloride of 1.365 gm/ml and contains two proteins immuno-precipitated with rabbit serum. Only the larger protein was recognized by immunoblotting using a convalescent-phase human serum. The protein composition of this virus differs from that reported for serotype 1 astrovirus, indicating heterogeneity in the capsid composition among astrovirus serotypes.

Adult↗
PubMed2000

Recombinant subunit ORF2.1 antigen and induction of antibody against immunodominant epitopes in the hepatitis E virus capsid protein.

A recombinant subunit antigen (ORF2.1), representing the carboxy-terminal 267 amino acids of the 660-amino-acid hepatitis E virus (HEV) capsid protein, was expressed in Escherichia coli and used for the immunisation of rats. Purified antigen formulated with either Aluminium Hydroxide Gel Adjuvant (Alum) or Titermax gave high and equivalent levels of antibody after three doses. Responses to two doses of 15, 75, or 150 microg antigen, formulated with Alum and given at 0 and 4 weeks, were also equivalent by 17 weeks after immunisation. Rats initially developed antibody to a wide range of linear epitopes in the ORF2.1 region, but by 27 weeks the predominant response detected by Western immunoblotting was restricted to the conformational epitope unique to ORF2.1 [Li et al. (1997) Journal of Medical Virology 52:289-300], a pattern that was also observed when comparing acute-phase patient serum samples with serum samples from convalescing patients. Antibody from immunised rats blocked the majority of patients' serum reactivity in enzyme-linked immunosorbent assay against both ORF2.1 (57-92% inhibition) and virus-like particles of HEV produced using the baculovirus system (74-97% inhibition). Together, these results suggest that the ORF2.1 subunit vaccine induces an antibody response against immunodominant, conformational epitopes in the viral capsid, which largely mimics that seen in convalescent patients, who are presumed to be immune to HEV infection.

Adjuvants, Immunologic↗
PubMed2000

Dynamic study of HBsAg and HBeAg in saliva samples from patients with hepatitis B infection: diagnostic and epidemiological significance.

Analysis of 505 cases history of patients among men with viral hepatitis demonstrates that HBV infected patients represent 68.9% of the total and that a non-parenteral rate of transmission is the most likely means of hepatitis B infection. Saliva and serum testing for the presence of specific HBV markers (HBsAg, HBeAg and HBV DNA) at different phases of the infection process were carried out to review the diagnostic and epidemiological value of saliva samples from patients with acute viral hepatitis B. The frequency of HBsAg detection by Enzyme Immune Assay (EIA) in saliva of patients in acute period was found to correlate with the frequency of its detection in serum. In early convalescence the frequency of detection of that antigen in serum (59.5% of patients) was significantly higher than in saliva (23.8%) (P < 0.001). The frequencies of HBeAg detection by EIA in saliva samples was significantly higher than that in serum samples in both acute phase (84.3% and 28.1% of patients, respectively) and in early convalescence (56.2% and 3.1% of patients, respectively). The study of frequencies of detection of these antigens in the dynamics of the disease up to the total recovery of patients (observations were carried out for the period of 60 days and longer) showed that in most patients there was a faster disappearance HBsAg from saliva than from serum. By the end of second month this antigen was detected in saliva of only 8.3% of patients whereas in serum in the same period HBsAg was detected in 33.3% of patients. HBeAg became undetectable in blood whereas HBs-antigenemia was still pronounced, and a month after the beginning of the disease it was not found in serum specimens. In saliva, HBeAg was detected in 95.8% of patients observed directly after admission. A month after the beginning of the disease it was detected in saliva of 66.7% of patients and, by the end of observation period, in 12.5% of patients recovered from viral hepatitis. HBV DNA revealed by PCR in saliva and serum of HBV-infected patients was detected in acute period not only in serum (84.6% of cases) but also in saliva (46.2% of cases). The data illustrate the diagnostic value of saliva and point to the possible role of saliva as a source of HBV infection.

Adolescent↗
PubMed2001

Activation of coagulation and fibrinolysis during dengue virus infection.

Dengue virus infection can induce mild dengue fever (DF) or severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in human. The pathogenesis of hemorrhage in dengue virus infection is not fully understood. Since hemostasis depends on the balance between coagulation and fibrinolysis, alternation of some coagulation parameters (platelet count and activated partial thromoboplastin time, APTT) as well as fibrinolytic parameters (tissue plasminogen activator, tPA and plasminogen activator inhibitor-1, PAI-1) were compared in 8 DHF/DSS and 17 DF patients. Patients showed thrombocytopenia, APTT prolongation, and tPA increase in the acute stage of disease, indicating activation of coagulation and fibrinolysis. The activation of coagulation and fibrinolysis in DHF/DSS patients was much more severe than DF patients. In the convalescent stage, a rise of PAI-1 level and platelet count with concomitant decline of tPA level and APTT returned to normal in both DHF/DSS and DF patients. Therefore, the activation of coagulation and fibrinolysis during the acute stage of dengue virus infection is offset by the increase of platelet and PAI-1 during convalescent stage. Taken together, these results suggest that the degree of coagulation and fibrinolysis activation induced by dengue virus infection is associated with the disease severity.

Adolescent↗
PubMed1975

Intravenous hyperalimentation in patients with head and neck cancer.

Intravenous hyperalimentation was utilized to support nutritionally 23 malnourished patients with major head and neck tumors during surgical treatment, radiotherapy, or the convalescent period. Fifteen patients were treated during the perioperative period and 12 survived. Six patients received convalescent nutritional support successfully 4 to 24 months following operation or radiation treatment. Two patients received treatment with hyperalimentation throughout a protracted course of radiation therapy. Weight gain, wound healing, and recovery were achieved in all but 3 patients. Subclavian vein thrombosis occurred in 1 patient, and catheter-related sepsis occurred in 2 patients. Otherwise, hyperalimentation was safe and efficacious in the debilitated patients. These patients may now become acceptable risks for surgical treatment or radiation therapy by nutritional repletion with intravenous hyperalimentation.

Body Weight↗
PubMed1995

Serum and urine beta-2-microglobulin in hemophagocytic syndrome.

BACKGROUND: Previous reports suggesting a correlation between lymphoproliferative disease and serum levels of beta-2-microglobulin (beta-2M) and in vitro data indicating a role of cytokines in the production of beta-2M prompted a study of serum and urine beta-2M concentration in patients with hemophagocytic syndrome (HPS), because no data were previously available for HPS, a pathologic state associated with excessive cytokines secreted from activated reactive/malignant lymphocytes and histiocytes. METHODS: Serum and urine beta-2M levels were measured in six children with HPS during active and convalescent phase and in other diseases. RESULTS: Serum and urine beta-2M levels during active phase HPS were significantly high not only in serum (median, 7.5 mg/l; range, 2.3-16.0 mg/l; P < 0.01), but also in urine (median, > 31,650 micrograms/gram Creatinine (gCr); range, 8179-236,333 micrograms/gCr; P < 0.01), compared with levels during convalescent phase HPS (median, 2.0 mg/l; range, 0.9-2.5 mg/l in serum and median, 338 micrograms/gCr; range, 223-585 micrograms/gCr in urine) and in control subjects with diseases such as acute lymphocytic leukemia (median, 2.3 mg/l; range, 1.0-2.8 mg/l in serum and median, 327 micrograms/gCr; range, 48-2684 micrograms/gCr in urine), infectious mononucleosis (median, 2.9 mg/l; range, 2.5-5.5 mg/l in serum and median, 348 micrograms/gCr; range, 80-1325 micrograms/gCr in urine), and Kawasaki disease (median, 2.8 mg/l; range, 1.5-3.3 mg/l in serum and median, 1016 micrograms/gCr; range, 214-4500 micrograms/gCr in urine). Noteworthy was the observation that urine beta-2M levels correlated closely with HPS disease activity. CONCLUSIONS: Urine beta-2M appears to be a useful marker for assessing disease activity in patients with HPS.

Adolescent↗
PubMed2000

Pre-operative endometrial thinning agents before hysteroscopic surgery for heavy menstrual bleeding.

BACKGROUND: Menorrhagia is one of the most common reasons for pre-menopausal women to be referred to a gynaecologist. Although medical therapy is generally the first approach, many will eventually require or request a hysterectomy. Hysterectomy is associated with a significant in-patient hospital stay and a period of convalescence that makes it an unattractive and unnecessarily invasive option for many women. Hysteroscopic endometrial ablation or resection offers a day-case surgical alternative to hysterectomy for these women. It is also a cheaper procedure than hysterectomy. Complete endometrial removal or destruction is one of the most important determinants of treatment success. Therefore surgery will be most effective if undertaken when endometrial thickness is less than 4mm, in the immediate post-menstrual phase, however there are often difficulties in reliably arranging surgery for this time. The other option is the use of hormonal agents which induce endometrial thinning or atrophy prior to surgery. The most commonly evaluated agents have been goserelin (a GnRH analogue) and danazol. Progestogens and other GnRH analogues have also been studied although less data are available. It has been suggested that the use of these agents, particularly GnRH analogues, will reduce operating time, improve the intra-uterine operating environment, and reduce distension medium absorption (this is the fluid used to distend the uterine cavity during surgery). OBJECTIVES: To investigate the effectiveness of gonadotrophin-releasing hormone (GnRH) analogues, danazol, and progestogens, when used for endometrial thinning prior to hysteroscopic surgery for menorrhagia, in improving the intra-uterine operating environment and treatment outcome after surgery. SEARCH STRATEGY: The Menstrual Disorders and Subfertility Group search strategy (see Review Group details) was used to identify randomised trials that had compared the use of these drugs with either each other, or placebo, or no pre-operative treatment. SELECTION CRITERIA: Trials were included if they compared the effects of these agents with each other, or with placebo or no treatment on relevant intra-operative and post-operative treatment outcomes. Only randomised studies were included in this review. DATA COLLECTION AND ANALYSIS: Eight studies met the inclusion criteria for this review. Four studies compared goserelin (a GnRH analogue) with no treatment or placebo. Three studies compared goserelin with danazol. One study compared progestogens, danazol and triptorelin (a GnRH analogue) with no treatment. Data was extracted independently by two reviewers. A third reviewer checked data extraction for accuracy and wrote to authors where relevant data was missing or unclear. Intra-operative parameters included endometrial thickness, duration of surgery, ease of surgery, distension medium absorption and complication rate. Post-operative outcomes compared were the proportion of women with amenorrhoea, post-operative menstrual loss and dysmenorrhoea, and the need for further surgery. Data on side-effects were also recorded. MAIN RESULTS: When compared with no treatment GnRH analogues are associated with a shorter duration of surgery, greater ease of surgery and a higher rate of post-operative amenorrhoea. Post-operative dysmenorrhoea also appears to be reduced. The use of GnRH analogues has no effect on intra-operative complication rates and patient satisfaction with this surgery is high irrespective of the use of any pre-operative endometrial thinning agent. GnRH analogues produce more consistent endometrial atrophy than danazol. For other intra-operative and post-operative outcomes any differences are minimal. Both GnRH analogues and danazol produce side-effects in a significant proportion of women, though few studies have reported these in detail. Little randomised data is available to assess the effectiveness of progestogens as endometrial thinning agents and the effect of any thinning agent

Danazol↗
PubMed2006

Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis.

BACKGROUND: Cholecystectomy is one of the most frequently performed operations. Open cholecystectomy has been the gold standard for over 100 years. Laparoscopic cholecystectomy was introduced in the 1980s. OBJECTIVES: To compare the beneficial and harmful effects of laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis. SEARCH STRATEGY: We searched TheCochrane Hepato-Biliary Group Controlled Trials Register (April 2004), The Cochrane Library (Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004), Web of Science (1988 to January 2004), and CINAHL (1982 to January 2004) for randomised trials. SELECTION CRITERIA: All published and unpublished randomised trials in patients with symptomatic cholecystolithiasis comparing any kind of laparoscopic cholecystectomy versus any kind of open cholecystectomy. No language limitations were applied. DATA COLLECTION AND ANALYSIS: Two authors independently performed selection of trials and data extraction. The methodological quality of the generation of the allocation sequence, allocation concealment, blinding, and follow-up was evaluated to assess bias risk. Analyses were based on the intention-to-treat principle. Authors were requested additional information in case of missing data. Sensitivity and subgroup analyses were performed when appropriate. MAIN RESULTS: Thirty-eight trials randomised 2338 patients. Most of the trials had high bias risk. There was no significant difference regarding mortality (risk difference 0,00, 95% confidence interval (CI) -0.01 to 0.01). Meta-analysis of all trials suggests less overall complications in the laparoscopic group, but the high-quality trials show no significant difference ('allocation concealment' high-quality trials risk difference, random effects -0.01, 95% CI -0.05 to 0.02). Laparoscopic cholecystectomy patients have a shorter hospital stay (weighted mean difference (WMD), random effects -3 days, 95% CI -3.9 to -2.3) and convalescence (WMD, random effects -22.5 days, 95% CI -36.9 to -8.1) compared to open cholecystectomy. AUTHORS' CONCLUSIONS: No significant differences were observed in mortality, complications and operative time between laparoscopic and open cholecystectomy. Laparoscopic cholecystectomy is associated with a significantly shorter hospital stay and a quicker convalescence compared with the classical open cholecystectomy. These results confirm the existing preference for the laparoscopic cholecystectomy over open cholecystectomy.

Cholecystectomy↗
PubMedDate not supplied

Chronic non-A, non-B hepatitis: ultrastructural and serologic studies.

Liver biopsies from five patients with chronic non-A, non-B (NANB) hepatitis were examined by electron microscopy for hepatocellular alterations. Circular fused membranes were observed within the cytoplasm of hepatocytes of four of the patients. Aggregates of intranuclear particles, measuring 22 +/- 2 nm in diameter, were also seen in two of the biopsies in which fused membranes were identified. Sera of all five patients formed precipitin lines detectable by counterimmunoelectrophoresis when reacted with serum from an individual convalescent from posttransfusion NANB hepatitis. Using this convalescent serum as an antibody source, complexes of 22 +/- 2 nm particles were identified in three of the chronic patient sera by immunoelectron microscopy. These observations suggest that at last one of the agents responsible for NANB hepatitis elicits both nuclear and cytoplasmic modifications. Furthermore, the 22 +/- 2 nm particles circulating in the sera of the chronic NANB patients may represent components related to NANB hepatitis agent.

Antigen-Antibody Complex↗
PubMedDate not supplied

Rheumatoid factor-like reactants in sera proven to transmit non-A, non-B hepatitis: a potential source of false-positive reactions in non-A, non-B assays.

Convalescent phase non-A, non-B (NANB) human and chimpanzee sera were utilized in a solid-phase radioimmunoassay (RIA) in an attempt to identify a specific NANB antigen in human plasma, plasma-derived pellets and NP-40 disrupted pellets proven to transmit NANB infection to chimpanzees. RIA reactivity was noted in 5 of 8 pedigreed NANB infectious plasmas, but did not appear to be virus-specific. The RIA reactive fraction: (i) had a density of 1.27 to 1.32 gm per cm3 in cesium chloride; (ii) showed immunoreactivity corresponding to normal IgM, but peak RIA activity coincided with an aberrant IgM having a peak sedimentation coefficient of 56 S, and (iii) eluted at higher pH (5.6 to 5.0) than normal IgM on chromatofocusing columns. The reactant shared properties with rheumatoid factor in that it was absorbed by aggregated IgG and was unstable to 2-mercaptoethanol, but it did not react in standard agglutination tests for rheumatoid factor. The reactant was detected in both the acute and chronic phase of NANB infections in chimpanzee and man. By reacting with IgG in presumptive NANB convalescent sera, this aberrant rheumatoid factor could simulate a NANB antigen and represent a cause of false-positive reactions in putative NANB assays.

Animals↗
PubMed1990

HBV-DNA detection by gene amplification in acute hepatitis B.

Serum samples from 62 women, inadvertently infected with hepatitis B virus in an in vitro fertilization program, were tested for the presence of hepatitis B virus-DNA using the polymerase chain reaction. Under conditions of a strict spatial separation of DNA extraction, amplification and product analysis, we succeeded in detection of as few as 360 hepatitis B virus particles per milliliter. Hepatitis B virus-DNA was detected with a high frequency during HBsAg and HBeAg antigenemia (98.5%) but also in the convalescent phase after appearance of antibody to HBsAg (18.2%). However, all patients with hepatitis B virus-DNA in convalescent sera were hepatitis B virus-DNA negative 3 to 6 mo later. All patients with HBeAg-positive samples showed hepatitis B virus-DNA positivity by polymerase chain reaction. For acute hepatitis, gene amplification restores the relationship between HBeAg and hepatitis B virus-DNA observed in serum from chronic hepatitis B patients and calls attention to the prolonged presence of hepatitis B virus-DNA in serum after generally accepted criteria for resolution of the infection have been reached.

Acute Disease↗
PubMed1997

Hepatic expression of the woodchuck hepatitis virus X-antigen during acute and chronic infection and detection of a woodchuck hepatitis virus X-antigen antibody response.

The expression and localization of the woodchuck hepatitis virus X-antigen (WHxAg) was examined and compared with other markers of a woodchuck hepatitis virus (WHV) infection using rabbit antisera generated against recombinant WHxAg produced in bacteria. Cellular fractionation studies showed that WHxAg was localized to the soluble and cytoskeletal fractions of the cell when assayed by immunoprecipitation of [35S]-met-cys labeled extracts derived from primary cultures of acute WHV-infected hepatocytes. Immunohistochemical examination of liver from chronic WHV-infected animals showed WHV core antigen (WHcAg) and WHxAg expression in non-neoplastic tissue. The WHxAg was found localized to the cytoplasm of infected cells, similar to WHcAg. WHxAg expression was diminished in the foci of altered hepatocytes and in hepatocellular adenomas but was found in only 1 of 11 hepatocellular carcinomas (HCC). Hepatic biopsies from woodchucks experimentally inoculated with WHV were examined during the acute phase of infection and during convalescence for WHcAg and WHxAg expression by immunohistochemistry. Concurrent expression of WHcAg and WHxAg was observed during the viremic phase of infection. The two antigens exhibited similar localization to the cell cytoplasm, similar distribution within the liver lobule, and similar patterns of clearance during convalescence. An immune response to WHxAg was documented in some woodchucks following acute WHV infection. These studies further define the woodchuck model of HBV infection and should allow for the investigation of the role of hepadnaviral X-antigen expression in the pathogenesis of chronic hepatitis and HCC.

Acute Disease↗
PubMed2003

Antibody response after RSV infection in children younger than 1 year of age living in a rural area of Mozambique.

Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group- and strain-specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross-reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains.

Amino Acid Sequence↗
PubMed2003

Correlation between increased platelet-associated IgG and thrombocytopenia in secondary dengue virus infections.

Although the public health impact of dengue is increasing rapidly, the mechanism of thrombocytopenia in this disease remains unknown. To elucidate this mechanism, the relationship between platelet-associated IgG (PAIgG) and platelet count in 53 patients in the acute phase of secondary dengue virus infection was investigated in a prospective-hospital-based study. A significant inverse correlation between the two parameters was found in these patients, while no correlation was observed in healthy volunteers. The low baseline platelet counts during the acute phase in 12 patients with secondary dengue virus infection significantly increased during the convalescent phase, while the increased PAIgG levels during the acute phase in these patients significantly decreased during the convalescent phase. Anti-platelet IgG autoantibody was detected rarely in the plasma of 53 patients with secondary dengue infection. The involvement of anti-dengue virus IgG was also shown in platelets from all of 8 patients in the acute phase of secondary dengue virus infection. These findings suggest that PAIgG formation involving anti-dengue virus IgG plays a pivotal role in the induction of transient thrombocytopenia during the acute phase of secondary dengue virus infection.

Acute Disease↗
PubMed1982

Further evidence for common antigens in herpes simplex and varicella-zoster viruses.

To elucidate the mechanism of heterologous antibody responses to herpes simplex virus (HSV) and varicella-zoster virus (VZV) which occur in some patients with HSV or VZV infections, stronger evidence was sought for the existence of cross-reacting antibodies to these viruses, using antibody absorption procedures. Absorption of sera from initial HSV infections with HSV antigen was found to abolish heterologous antibody titer rises to VZV, as demonstrated in complement fixation, neutralization, and anti-complement immunofluorescence test systems. In most instances, convalescent-phase titers to heterologous VZV were reduced by HSV absorption to levels comparable to those in the acute-phase serum, indicating that cross-reacting antibodies were, in fact, responsible for the heterologous antibody titer rises. Absorption of convalescent-phase sera from HSV or VZV patients with homologous antigen also abolished or greatly diminished immunoprecipitating activity with the heterologous antigen, furnishing additional evidence of the existence of cross-reacting antibodies. Absorption of sera with insolubilized IgG to re-remove rheumatoid factor, which was present in a number of the sera studied, had no effect on either homologous or heterologous antibody titer increases. The demonstration of cross-reacting antibodies to HSV and VZV supports the concept that these two human herpesviruses share common antigen(s).

Antibodies, Viral↗
PubMed1983

Characterization of a precipitating antigen detected in the serum of patients with viral hepatitis.

During a search for the aetiological agent of non-A non-B hepatitis, a precipitating antigen was detected in the sera of some patients during the acute phase of their illness. The antigen was detected by agar gel diffusion using antibody from convalescent sera obtained from patients with non-A non-B hepatitis, and from haemophiliac sera. The antigen was usually detected early in the patient's illness, disappearing as liver function tests returned to normal. In some patients specific antibody appeared during the convalescent phase of the disease. The antigen does not appear to be specific for non-A non-B hepatitis, as it could be detected with similar frequency in patients with hepatitis A or hepatitis B and some patients with other liver disorders. Biochemical and biophysical studies suggest that the antigen is probably an abnormal lipoprotein produced as a result of acute liver damage.

Antigens↗
PubMed1983

Protection of Lassa virus-infected guinea pigs with Lassa-immune plasma of guinea pig, primate, and human origin.

Lassa virus-immune plasma has been used to treat human Lassa fever patients; however, criteria for plasma selection were based arbitrarily on available serologic tools and protective efficacy was never directly assessed. To test the validity of plasma therapy for Lassa virus infections in an animal model, and to develop biologically relevant criteria for selection of protective immune plasma, inbred, strain 13 guinea pigs were infected with a lethal dose of Lassa virus and treated with various Lassa-immune plasmas obtained from guinea pigs, primates, and convalescent human patients. Neutralizing antibody titers were determined in a virus dilution, plaque reduction test, and were expressed as a log10 plaque-forming units (PFU) neutralization index (LNI). All guinea pigs treated with immune plasma 6 ml/kg/treatment on days 0, 3, and 6 after virus inoculation were protected, provided the LNI exceeded 2.0. Plasmas obtained from donors in early convalescence (32-45 days) had low titers of N-antibody (LNI less than 2) and failed to confer protection, despite high titers of Lassa antibody measured in the indirect fluorescent antibody (IFA) test. Higher doses of marginally titered plasma conferred increased protection. The degree of protection and suppression of viremia was closely associated with LNI an not IFA titers. Administration of low-titered plasma did not result in immune enhancement. A high dose of human plasma from Liberia (12 ml/kg/treatment) was required to confer complete protection to guinea pigs infected with a Lassa virus strain from Sierra Leone (LNI = 1.6), while a lower dose (3 ml/kg/treatment) was sufficient for protection against a Liberian strain (LNI = 2.8), suggesting that a geographic matching of immune plasma and Lassa virus strain origin may increase treatment success. These studies support the concept of plasma therapy for Lassa infection and suggest that the plaque reduction neutralization test is more appropriate than the IFA test for predicting protective efficacy of passively administered plasma.

Animals↗
PubMed1984

Indirect and reverse radioimmunoassays and their apparent specificities in the detection of antibodies to enteroviruses in human sera.

Indirect radioimmunoassays (RIAs) of IgM and IgG antibodies to enteroviruses have been developed, using coxsackieviruses B1 and B3, and echoviruses 11 and 30. The titres of IgM and IgG were assayed in paired sera from patients infected with one of these viruses or coxsackieviruses A7, A9, A16, B2, B4, B5 or echoviruses 4, 17, or 25. Both IgM and IgG were found in almost all serum pairs with each of the four viruses used as an antigen, and there were no certain differences between titres obtained with homologous and heterologous antigens. The convalescent phase specimens contained significantly higher titres compared with the acute phase specimens, the difference being most pronounced for IgG. Of the specimens from patients with nonenterovirus infections, a relatively high percentage contained IgM and IgG against enterovirus antigen. However, no increases in titres were seen between acute and convalescent specimens. When specimens from younger patients, aged 2 days to 22 months, without evidence of enterovirus infections, were assayed with enterovirus antigen, the frequency of IgM titres was seen to increase with age. Almost all specimens from newborns were negative, whereas the specimens from 12- to 22-month-old children showed a high frequency of IgM titres. In specimens from patients aged 2 days to 8 months, the ratio between IgM and IgG titres increased with age, probably due to a loss of maternal IgG. The IgG titres in specimens from 8.5- to 22-month-old children were similar to the titres of specimens from the patients with nonenterovirus infections. A reverse IgM assay was also developed, using the same viruses and serum specimens as for the indirect assays. In contrast to the indirect IgM assay, the reverse IgM assay was apparently type specific, provided that the amount of labeled virus was carefully standardized. The reverse IgM RIA detected and identified antibody responses better than the neutralization test. Attempts to develop a reverse IgG assay were promising concerning the specificity, but the sensitivity was low.

Antibodies, Viral↗

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