Poor IgM antibody response to hepatitis B core antigen in infants with hepatitis B virus infection.
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Antibody Formation↗
Biomedical subjects
H S Margolis
Publications and source records attributed to H S Margolis.
Routine prenatal screening for hepatitis B surface antigen.
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Carrier State↗
Appearance of immune complexes during experimental hepatitis A infection in chimpanzees.
Circulating immune complexes (CICs) were detected during the course of experimental hepatitis A virus (HAV) infection in 8 of 9 chimpanzees. In all cases, the predominant class of antibody detected in the CIC was IgM. The appearance of IgM-CIC usually preceded the onset of liver enzyme elevations, and in all instances, the appearance of IgM-CIC correlated with the presence of IgM anti-HAV. Six of 8 animals tested had significant depression of C3 concentrations during the course of infection, and this depression occurred at the peak of CIC activity. Immunohistologic studies demonstrated granular deposits of IgM localized in sinusoidal cells during peak of IgM-CIC activity. IgM-CICs appear to be a fairly consistent finding during HAV infection and probably represent the viremic phase of the disease. However, they do not appear to mediate hepatocellular injury by direct action on hepatocytes.
Animals↗
Large scale production of hepatitis A virus in cell culture: effect of type of infection on virus yield and cell integrity.
Approaches to cell culture propagation of hepatitis A virus (HAV) have used either acute infection by passage of infected cell lysates or supernatants into uninfected cells or the passage of persistently infected cells. The findings presented here demonstrate that the growth and recovery of purified virus from foetal rhesus monkey kidney (FRhK4) cells persistently infected with HAV isolate HAS-15 decreased over a 2 to 3 month period. In contrast, high multiplicity acute infection of FRhK4 cells with purified HAS-15 HAV resulted in degeneration of the cell monolayer 2 to 3 weeks later. Large scale propagation of acutely infected cells followed by traditional picornavirus purification procedures reproducibly yielded milligram amounts of purified virus.
Animals↗
Characteristics of chemically aggregated IgM in an immunoglobulin class-specific immune complex assay.
Immune complexes have been implicated in the pathogenesis of a number of infectious diseases. The predominant immunoglobulin class associated with circulating immune complexes is IgG, although immune complexes containing IgM have been described. The role of IgM immune complexes in disease pathogenesis has been difficult to characterize due to the lack of a reliable in vitro model. Immunoglobulins aggregated with bis-diazotized benzidine (BDB) are known to function as model immune complexes. We have developed an IgM immune complex using BDB-aggregated IgM which can be used as a reference in a conglutinin-based immune complex assay. Using this assay system, humans and chimpanzees with acute hepatitis A were found to have circulating immune complexes that contained IgM as the predominant antibody.
Animals↗
Intradermal hepatitis B vaccination in an abbreviated schedule.
Two low-dose intradermal regimens for hepatitis B vaccination were compared with the standard 1 ml dose administered intramuscularly to healthy, 22-42 year old individuals. All regimens were administered in an abbreviated time schedule. Nineteen individuals (ID-1 group) received three 0.1 ml (2 micrograms) doses intradermally at times 0, 1 month and 4 months. Twenty-four individuals (ID-2 group) received two injections of 0.2 ml (4 micrograms) each intradermally at time 0 and one 0.1 ml (2 micrograms) injection 4 months later. Twenty individuals (IM group) received the recommended three 1.0 ml (20 micrograms) doses intramuscularly at times 0, 1 month, and 4 months. No significant adverse reactions were attributable to the intradermal administration of vaccine although the majority of vaccinees developed small areas of induration and hyperpigmentation at the injection site that persisted for several months. One month following the last injection, all vaccinees had developed anti-HBsAg antibodies. One hundred percent of ID-1 and IM vaccinees and 95% of ID-2 vaccinees had protective levels of antibody (greater than or equal to 10 mIU ml-1). The geometric mean titre (GMT) for the IM group (2692 mIU ml-1) was somewhat higher than for the ID-1 (1230 mIU ml-1) and the ID-2 (851 mlU ml-1) groups, but the differences were not statistically significant. Since anti-HBs antibodies are thought to confer protection against hepatitis B, these results suggest that a shortened regimen of intradermal vaccine may be effective in healthy adults. However, no efficacy study has yet been done with intradermal hepatitis B vaccine.
Adult↗
Experimental transmission of the delta virus to a hepatitis B chronic carrier chimpanzee with the development of persistent delta carriage.
A delta virus (DV) infection was experimentally transmitted to a hepatitis B chronic carrier chimpanzee. The infection was monitored by the examination of liver biopsy materials with the use of FITC-labeled human anti-delta IgG or by an indirect immunoperoxidase staining technique and by measurement of the serum alanine aminotransferase (ALT) activity. Three different antibody enzyme immunoassays (EIAs) were developed for assessment of the serologic response: 1) blocking assay, 2) IgM-specific capture assay, and 3) IgG-specific capture assay. An antigen-specific EIA was also developed for monitoring delta antigen in the serum. The results indicate that a superinfection with the DV produced a biphasic ALT response concomitant with the appearance of the delta antigen in biopsy materials. The persistence of these markers over the observation period (350 days) indicates the development of a persistent DV infection.
Alanine Transaminase↗
Pathologic and ultrastructural changes of acute and chronic delta hepatitis in an experimentally infected chimpanzee.
A hepatitis B surface antigen (HBsAg) chronic carrier chimpanzee experimentally superinfected with delta virus (DV) developed chronic DV infection. Over a period of 12 months, serologic and biochemical changes were correlated with morphologic abnormalities of the liver. Severe hepatic necrosis and inflammation accompanied the initial acute episode of hepatitis on Day 35 after inoculation, followed by complete resolution of these lesions over the next 3 months. A second episode of hepatitis occurred on Day 145, and severe necrosis and inflammation recurred along with the reappearance of delta antigen in the hepatocytes. Delta antigen persisted in the liver following the second episode of hepatitis and has remained positive throughout the observation period of 1 year. During the initial acute episode, the hepatocytes exhibited foamy cytoplasmic changes resembling microvesicular fat. However, ultrastructural studies of the same cells revealed only vacuolization of the cytoplasm without evidence of fat droplets. The inflammatory infiltrate during both episodes of hepatitis demonstrated a striking predominance of macrophages over lymphocytes. Hepatocyte abnormalities observed by electron microscopy included vacuoles, proliferated endoplasmic reticulum, and tubules similar to those seen in posttransfusion non-A, non-B hepatitis. However, the tubular and reticular abnormalities coincided with delta antigen expression in liver biopsies detected by direct immunoperoxidase staining and abnormal alanine aminotransferase levels in the serum, which suggests a possible causal relationship. Nuclear abnormalities were not seen.
Acute Disease↗
Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial.
Hepatitis B is a serious disease of global significance. In developing countries, hepatitis B virus (HBV) infection and its sequelae rank among the public health problems of highest priority. Infants born to mothers who are chronic carriers of HBV are at particularly high risk of acquiring infection and becoming chronic HBV carriers. The efficacy of hepatitis B vaccine alone in preventing the transmission of HBV to infants born to HBV carrier mothers was determined in a double-blind placebo-controlled trial. Infants received plasma-derived vaccine at birth, 1 month, and 6 months of age. Of 180 infants born to hepatitis B surface antigen (HBsAg)-positive mothers, equal numbers received National Institute of Allergy and Infectious Disease (NIAID) vaccine, Beijing Institute of Vaccine and Serum (BIVS) vaccine, and placebo. The cumulative seroconversion to the vaccines at 1 year of age was 95% and 75%, respectively. Vaccine efficacy as measured by the prevention of HBsAg-positive events was 88% for the NIAID vaccine and 51% for the BIVS vaccine. Vaccine efficacy was similar among infants born to hepatitis Be antigen-positive mothers. Because of the low efficacy of the BIVS vaccine, an additional group of 28 infants was given vaccine and hepatitis B immune globulin at birth. The resulting efficacy was 83%. The results of this trial indicate that hepatitis B vaccine alone can substantially reduce perinatally acquired HBV infection and the resulting chronic carrier state.
Carrier State↗
Unrelatedness of factor VIII-derived non-A/non-B hepatitis and hepatitis B virus.
A DNA hybridization assay was used to detect hepatitis B virus (HBV)-specific DNA sequences in extracted sera obtained from chimpanzees infected with HBV, hepatitis A virus (HAV), and a factor VIII-derived non-A/non-B (NANB) agent. The results did not reveal any HBV-DNA homology with sera obtained from animals infected with HAV or factor VIII-derived NANB. Sera obtained from two HBV-infected chimpanzees demonstrated that HBV-specific DNA could be detected during the acute phase of the disease. In addition, an HBV-specific DNA-dependent DNA polymerase assay did not demonstrate any statistically significant activity in 12 of 12 NANB acute-phase specimens or in 6 of 6 NANB chronic-phase specimens. These results suggest that the factor VIII-derived NANB agent is unrelated to HBV.
Animals↗
Type 49 Streptococcus pyogenes: phage subtypes as epidemiological markers in isolates from skin sepsis and acute glomerulonephritis.
Studies of group A, M type 49 streptococci from England, Trinidad and Alaska indicate that isolates of this serotype often differ with respect to phage subtype from one geographical area to another, but are generally homogeneous in one place at one time. The findings support the conclusion that acute glomerulonephritis can be associated with a variety of phage subtypes of M type 49 streptococci. In outbreaks of skin sepsis without nephritis in England, the phage subtypes of M type 49 streptococci isolated from skin lesions of meat handlers were the same as those recovered from skin lesions of non-meat handlers in the same community. The findings on the Trinidad isolates suggest that M type 49 streptococci of one phage subtype may persist in a population for 9 years and may result in a second outbreak of acute glomerulonephritis. In an Alaska Eskimo population in whom acute glomerulonephritis was occurring, most of the M type 49 isolates available for testing were of a single phage subtype. Equally prevalent in this population were group A streptococci that exhibited the same T antigen as the type 49 isolates but differed in their serum opacity reaction and phage subtype. This apparently related strain was not typable with available M antisera but showed functional evidence of M protein and is probably a new M type.
Alaska↗
Haemophilus influenzae disease in Alaskan Eskimos: characteristics of a population with an unusual incidence of invasive disease.
During 1971-77 the incidence of bacterial meningitis among Alaskan Eskimos was 84.4 cases per 100 000 population per year, which is more than 10 times that for most other U.S. populations. Haemophilus influenzae (HI) accounted for 68% of meningitis cases. The average annual incidence of HI disease per 100 000 children below 5 years of age was 409 for patients with meningitis only and 491 for patients with all systemic HI disease. Children with HI meningitis in Alaska tended to be younger than those in other U.S. populations, 98% of the children affected being less than 18 months of age. The risk for all HI disease was 2.4% during the first year of life. The spectrum of HI disease in Alaska differs from that in other populations in that no patient had epiglottitis and 5% of children had recurrent HI disease. Alaskan newborns and children over 4 years old had HI anticapsular antibody titres that were nearly thrice those for children of similar ages in other U.S. populations (p less than 0.005). The pharyngeal carriage of HI type b (5%) and the rectal carriage of Escherichia coli K100 (2%), an organism with a capsule antigenically similar to HI type b, did not differ from those in other populations. The high incidence of disease almost exclusively in the very young and the early development of antibody in this population suggest that the high rate of disease is due to early exposure to HI type b rather than to an unusual susceptibility to HI type b.
Adolescent↗
Iron deficiency in children: the relationship between pretreatment laboratory tests and subsequent hemoglobin response to iron therapy.
The goal of detecting iron deficiency in children is to identify those whose Hb concentration will rise in response to treatment with iron. In a controlled treatment trial conducted among Eskimo children, we examined the effectiveness of various measures of iron nutrition in predicting a response to iron therapy (greater than 1.0 g/dl rise in Hb). A response was seen in 43%, and an additional 26% had an intermediate response (0.5 to 1.0 g/dl rise). When individual Hb values were expressed as SD scores of the Hb distribution of a reference population, a marked skew toward low scores was seen before treatment. After treatment, the distribution became more Gaussian, indicating that iron deficiency had been the major cause of anemia. Serum ferritin, transferrin saturation, and free erythrocyte protoporphyrin levels moved toward normal with treatment, however, none of the tests used was very effective in distinguishing individuals who would have a response t Hb from those who would not (sensitivities: 63 to 42%, specificities: 45 to 61%). Laboratory measures of iron nutrition were far more helpful in depicting the iron status of the population than they were in distinguishing iron-responsive from nonresponsive individuals.
Adolescent↗
Acute glomerulonephritis and streptococcal skin lesions in Eskimo children.
Poststreptococcal acute glomerulonephritis often follows impetigo and can occur in epidemics. From 1975 through 1977, an epidemic of poststreptococcal acute glomerulonephritis occurred in Alaska. Fifty children required hospitalization, while 25 less seriously ill children were treated as outpatients. Sixty-seven percent of these 75 children had direct evidence of recent skin infections. Serotypes 49-14 and NT-14 were the most common streptococcal isolates. In villages in the epidemic area, approximately 15% of children had impetigo and more than 60% of lesions cultured were positive for group A streptococci. Impetigo rates in the epidemic area were similar to those found in nonepidemic areas. However, the introduction of the nephritogenic streptococcal serotypes not recently present in this population apparently led to the development of the epidemic.
Acute Disease↗
Arctic trichinosis: two Alaskan outbreaks from walrus meat.
The arctic form of Trichinella spiralis that infects terrestrial and marine mammals is of importance in public health because persons living in arctic regions still depend on wild animals for economic subsistence. In 1975, an extended common-source epidemic of trichinosis attributed to consumption of walrus meat involved 29 persons in Barrow, Alaska. Of those persons eating this meat, 64% became ill, and the rate of infection of persons eating meat prepared with little or no cooking was four times as great as that of persons eating cooked meat. One year later a second outbreak occurred when a family ate partially cooked meat from an infected walrus. Clinical illness differed little from the disease acquired in temperature climates; however, only 70% had a positive bentonite flocculation titer, whereas 96% had eosinophilia. These epidemics of trichinosis are the first reported in Alaska to be associated with the consumption of walrus meat.
Alaska↗
An outbreak of influenza aboard a commercial airliner.
A jet airliner with 54 persons aboard was delayed on the ground for three hours because of engine failure during a takeoff attempt. Most passengers stayed on the airplane during the delay. Within 72 hours, 72 per cent of the passengers became ill with symptoms of cough, fever, fatigue, headache, sore throat and myalgia. One passenger, the apparent index case, was ill on the airplane, and the clinical attack rate among the others varied with the amount of time spent aboard. Virus antigenically similar to A/Texas/1/77(H3N2) was isolated from 8 of 31 passengers cultured, and 20 of 22 ill persons tested had serologic evidence of infection with this virus. The airplane ventilation system was inoperative during the delay and this may account for the high attack rate.
Adult↗
Possible association between maternal indomethacin therapy and primary pulmonary hypertension of the newborn.
Indomethacin purportedly arrests premature labor by inhibiting the production of prostaglandins. Animal experimentation has demonstrated that prostaglandins are involved in the neonatal rerouting of the circulation. Experience with two neonates with disorders circulatory adjustment at birth following prenatal exposure to indomethacin indicates that indomethacin may interfere with these adjustments in man and favor the development of the serious oxygen dependency known as primary pulmonary hypertension of the newborn.
Adolescent↗
Altered urinary kallikrein excretion in human hypertension.
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Adolescent↗