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Tourist hepatitis, antibodies to hepatitis A virus and immune serum globulin prophylaxis.

Immune serum globulin prophylaxis for foreign travellers should be reserved for those at high risk having no immunity against hepatitis A. In this study from Sweden the incidence of tourist hepatitis in different age groups was correlated to the prevalence of antibodies to hepatitis A virus (anti-HAV) in the population. 58% of individuals over 50 years had anti-HAV and travellers in these ages seldom experienced "tourist hepatitis". In younger age groups a low prevalence of anti-HAV (11%) was combined with a higher incidence of tourist hepatitis.

Adult↗

Antibody to the hepatitis B virus-associated delta-agent in immune serum globulins.

Fifty lots of immune serum globulin prepared by four United States manufacturers between 1944 and 1977 were tested for the presence and titer of antibody to the hepatitis B virus-associated delta-agent. Anti-delta was detected in 28 of the 50 lots (56%) of immune serum globulin at titers ranging from 1:10 to 1:400. Anti-delta was present in 75% (6 of 8) of lots produced between 1962 and 1965, in 77% (17 of 21) produced between 1967 and 1970, in 45% (5 of 11) produced between 1971 and 1972 and in none (0 of 9) produced since 1973. A single lot of globulin prepared from plasma that was collected in 1944 from United States Army soldiers also contained detectable anti-delta. These data indicate that delta-infection has been occurring among hepatitis B surface antigen (HBsAg) carriers in the United States since the 1940s. The decrease in prevalence of anti-delta in immune serum globulin lots coincided with the start of routine HBsAg screening of blood and plasma. The elimination of HBsAg-positive units from plasma pools has reduced levels of HBsAg and anti-delta and should have decreased the risk of transmission of both type B hepatitis and delta-hepatitis by plasma products.

Blood Donors↗

Efficacy of modified human immune serum globulin in the treatment of experimental murine infections with seven immunotypes of Pseudomonas aeruginosa.

Modified immune serum globulin, prepared from human immune serum globulin by a nonenzymatic method, is apparently safe for intravenous administration to humans. The efficacy of the preparation was determined in experimental murine infections with seven immunotypes of Pseudomonas aeruginosa. Intravenously administered 0.85 percent NaCl, 0.3 m glycine, and 10 percent human albumin did not protect against lethal pseudomonas infection, whereas modified immune serum globulin given by the same route did protect mice. In the mouse protection test, the mean dose of the preparation that saved 50 percent of mice infected with any of eight strains of P. aeruginosa was 480 mg/kg (range, 12-2,333 mg/kg). For five strains the 50 percent effective dose was smaller than 200 mg/kg. There was no correlation between the efficacy of modified immune serum globulin in the mouse protection test and titers of antibody, as determined by bacterial agglutination. Therapy of pseudomonas infection in mice with modified immune serum globulin was followed by a prompt and persistent decrease in the numbers of intraperitoneal bacteria. This finding is consistent with the interpretation that modified immune serum globulin acts primarily as an opsonin and not as an antitoxin. Modified immune serum globulin may prove to be useful in the treatment of human infections.

Agglutination Tests↗

The action of macrophages and immune serum on growth of Babesia microti in short-term cultures.

The effect on growth of B. microti of macrophages from normal or B. microti recovered animals was tested in short-term cultures. Normal macrophages did not or only slightly inhibited parasite growth. When immune serum was added to the normal macrophage containing cultures, inhibition greater than that produced by immune serum alone was observed. Macrophages from immune animals had an inhibitory effect on parasite growth even in the absence of immune serum. Inhibition of B. microti growth was greater in cultures containing immune serum and immune macrophages than in cultures containing either immune serum or immune macrophages alone. Supernatants from B. microti cultures which contained immune macrophages or macrophages which had been stimulated by addition of immune serum inhibited parasite growth while cell free supernatant from cultures which contained no macrophages or normal macrophages did not. At 72 and 96 hr of culture erythrophagocytosis by macrophages was more prominent in immune serum containing B. microti cultures than in B. microti cultures not containing immune serum. More macrophages were retained in the immune serum containing cultures than in cultures not containing immune serum. Alternate culture-hamster passage yielded a B. microti strain which grew better in hamster erythrocyte short-term cultures than did the original strain.

Animals↗

[Anti-Brucella immunity transferred by immune serum and that transferred by splenic lymphocytes cannot be added].

Immune serum and spleen cells from mice vaccinated with a cell-wall fraction (PG) from Brucella were previously shown to transfer a good protection to mice against a virulent Brucella challenge. This protection estimated by spleen and liver time-course infection was similar to that afforded by vaccination. In present experiments, DBA/2 mice were first transferred with either immune serum from infected mice, splenic cells from mice intravenously vaccinated with PG fraction 28 days previously, or both immune serum and splenic cells. In this case, the serum was either injected before the challenge, as were the splenic cells, or 2 days after it in order to reduce the lowering effect of the serum on level of initial colonization of the spleen. The transferred mice were then intravenously challenged with the virulent strain B. abortus 544 and liver and spleen counts were performed on groups of five mice weekly up to six weeks. Immune serum and splenic cells from vaccinated mice were again shown to strongly reduce the time-course of splenic infection. However addition of both effects was observed for a short time only two and three weeks post-challenge and only when the serum was injected after the challenge. In contrast, no additive or even an antagonistic effect was observed after the 21st day. Liver infection was not notably modified by both immune serum or splenic cells (except increment of initial colonisation by serum) until the 21st day when both helped reduce the course of infection. However again no additive effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Removal of anticomplementary activity from human immune serum globulins by treatment with purified human plasmin.

Human immune serum globulin preparations were treated with highly purified human plasmin to remove their anticomplementary activity. The extent of anticomplementary activity removed and the amount of fragmentation obtained from immune serum globulin preparation depended upon the amount of plasmin added and the length of incubation time. The enzymatic reaction was stopped by removing plasmin with bentonite adsorption. Two types of plasmin-treated immune serum globulin that may be used for intravenous injection were obtained. One was a more fragmented product (35 to 45%) with lower anticomplementary activity, the other was a less degraded product (15 to 20%) with slightly higher anticomplementary activity. Antibody content of the former preparation was somewhat reduced while that of the latter preparation was virtually unchanged from the untreated immune serum globulin.

Complement System Proteins↗

[A new immune serum globulin preparation for intravenous administration (author's transl)].

A new immune serum globulin preparation has been developed which is suitable for i.v. administration. This product was prepared from Cohn fraction II by selective reduction with dithiothreitol of one or more of the interchain disulfide bonds between the heavy chains and subsequent alkylation of the formed sulfhydryls (about 8--10 per 160 000 daltons) with iodoacetamide. The of these chemical reactions has been termed MISG (modified immune serum globulin). It is free of anticomplement activity, contains essentially all of the antibody potency of immune serum globulin, sediments as essentially a single entity with a sedimentation coefficient of about 7 S, has been freed of all reactants, is non-toxic, and in rabbits is antigenically with normal human immune serum globulin. MISG with its Fc fragment portion intact maintains its complement mediated function as evidenced by its opsonic activity against bacteria. MISG had been tested extensively in vitro, in animals, and in humans. Half-life measurements in humans averaged 22.4 days (range 15.5--28.7 days) and efficacy was demonstrated in a 2-year crossover clinical study in which MISG was compared with normal immune serum globulin administered i.m.

Chemical Phenomena↗

Effect of immune serum and its immunoglobulin fractions on hamsters challenged with Treponema pallidum ssp. pertenue.

Passive transfer of frambesial immune serum is capable of conferring complete protection on hamsters against challenge with Treponema pallidum ssp. pertenue. Treponemicidal activity in the pooled immune serum is relatively high. Immune serum and its immunoglobulin fractions, especially IgG2, also killed T. pallidum ssp. pertenue in vitro. Treponemicidal activity was present only when immune serum was administered to hamsters within a short time (three days) of frambesial challenge. By contrast, administration of pooled immune serum to hamsters infected for more than one week failed to reduce the number and size of lesions and the weight and number of treponemes in the lymph nodes. These results suggest that hamsters can develop the humoral components necessary to protect them against frambesial challenge, but these components are unable to destroy treponemes at the primary foci of infection.

Animals↗

Expulsion of Nematospiroides dubius from the intestine of mice treated with immune serum.

This paper describes experiments which demonstrated that the survival of Nematospiroides dubius was severely impaired in mice treated with immune serum. CFLP donor mice were given a series of infections ranging from 25 to 200 infective larvae, at weekly intervals for 6 weeks. The mice were treated with anthelmintic on day 21 and/or day 28 to prevent the accumulation of lethal numbers of parasites in the intestine, and were bled between day 42 and day 49. Female NIH recipient mice were given a total of 2.0-2.5 ml of immune serum i/p., in several separate smaller doses at various times in relation to the day of infection. Between the administration of immune serum begun during the first 4 days of infection and the animals being killed within the next 3 weeks, the mice harboured fewer worms than control animals, the worms were stunted and their fecundity was greatly reduced. Furthermore, these worms were subsequently lost from the intestines of treated mice, during and after the fourth week of infecton. These effects on N. dubius were not observed when mice were given normal serum nor when immune serum was administered after day 6 of the infection. The delayed rejection of adult worms from mice treated with immune serum is of particular significance and suggests that immune serum contained factors which facilitated the expression of a second component in worm expulsion not nornally effective in a primary infection. The possible immunologcal mechanisms underlying these findings are discussed and related to the immunosuppression which N. dubius is known to induce in the host.

Animals↗

Synergistic interaction between immune serum and thoracic duct cells in the adoptive transfer of rapid expulsion of Trichinella spiralis in adult rats.

Rapid expulsion of Trichinella spiralis could be transferred to naive adult rats with thoracic duct lymphocytes and immune serum. Thoracic duct cells collected from Days 3-5 and immune serum collected on Day 28, respectively, after infection were effective. Both cells and serum were unable to transfer rapid expulsion when given alone, even in large volumes. Recipients of immune serum and cells eliminated a significantly higher number of larvae than control rats by 1 hr after challenge with muscle larvae. Rapid expulsion produced 30-80% larval worm rejection but could not be increased by the transfer of more cells or immune serum. Mucus trappings did not appear to play a role in the rejection process. After transfer of 2 x 10(8) cells and 4.0 ml immune serum, rapid expulsion persisted for less than 1 week. However, after adoptive transfer of cells alone, the gut remained functionally receptive to the passive transfer of immune serum for 7 weeks. Therefore, the changes effected by transfer of cells were long lived in contrast to the 1 week, or less, of functional persistence by transferred immune serum. The data indicate that two separate processes, one cell mediated and the other immune serum mediated, interact synergistically in the intestine and lead to the expression of rapid expulsion.

Animals↗

Inhibition of in vitro growth of Plasmodium falciparum by immune serum from monkeys.

Three owl monkeys that had been immunized against the Camp strain of Plasmodium falciparum by infection were treated with chloroquine and rechallenged with parasites. Immune serum caused a dose-dependent, time-dependent inhibition of in vitro parasite growth. Heat-inactivation eliminated nonspecific inhibition by normal monkey serum without diminishing immune inhibition. Purified IgG from immune serum inhibited parasite growth. Serum taken immediately before the second challenge did not inhibit growth in vitro at a 1:10 dilution, although the monkeys successfully resisted the in vivo challenge. However, immune sera from all three monkeys taken two to four weeks after in vivo challenges were inhibitory, but sometimes detection required 20% serum. Growth inhibition in vitro by 10% serum was a poor predictor of in vivo protective immunity. Undiluted blood containing higher antibody levels (which are boosted by challenge), combined with additional immune mechanisms, may explain the protection observed in vivo.

Animals↗

Immunoregulatory effects of intravenous immune serum globulin therapy in common variable hypogammaglobulinemia.

Because of evidence of immunoregulatory effects of short-term administration of pooled donor gamma globulins, the effects of intravenous immune serum globulin were studied in nine adult patients with common variable hypogammaglobulinemia over a two-year period. Baseline assessment prior to immune serum globulin replacement included evaluation of B cell function, suppressor cell activity, and T cell subsets. These analyses were subsequently performed during the course of a first-year treatment period of intravenous immune serum globulin at doses of 100 to 200 mg/kg per month and a second-year trial at doses of 300 to 400 mg/kg per month. Five patients were re-evaluated following discontinuation of the intravenous immune serum globulin therapy for four months between the first and second treatment periods. During both treatment periods with intravenous immune serum globulin, suppressor cell activity increased markedly compared with baseline, and declined following discontinuation of drug therapy in the five patients. Suppressor cell activity was reversed by either irradiation of the T cell fraction or removal of the T8-positive cell fraction by flow cytometry. There was a reduction in the absolute number of total lymphocytes, the T3-positive cells (total T cells), and the T4-positive cells (helper cells) following intravenous immune serum globulin therapy; however, the percentages of the T cell subsets did not change significantly. Following immune serum globulin therapy, the number of T8-positive cells was not significantly changed but the T4:T8 ratio decreased from 2.1 at baseline to 1.5 after therapy (p greater than 0.05). These data demonstrate that long-term intravenous immune serum globulin administration modulates the immune system by increasing suppressor T cell functional activity but is not accompanied by changes in the number of T8-positive cells in the peripheral blood.

Adult↗

Persistent serum immune complexes in syphilis.

Serum immune complexes were estimated by a polyethylene glycol precipitation method in 51 patients with early syphilis. The immune complexes were increased in 41% of patients before treatment and decreased to normal limits in only 56% during treatment. The results of the specific antireponemal tests using dissolved immune complexes show that antibodies from the immune complexes are specific antibodies.

Adolescent↗

Studies of escherichia coli in gnotobiotic pigs. V. Evaluation of the effects of oral and parenteral administration of immune serum.

The effects of orally and/or parenterally administered immune serums were evaluated in 36 gnotobiotic pigs infected with an enteropathogenic strain of Escherichia coli. Pigs were euthanatized at predetermined time intervals between 6 and 48 hours prostinfection. The results were evaluated on the basis of: 1) clinical observations, 2) necropsy observations, 3) counts of viable E. coli in segments of the small intestine, 4) attempts to isolate E. coli from the heart, liver, and bile, 5) microscopic examination of fixed intestinal sections to determine the location of E. coli and morphologic evidence of the host response, and 6) determination of the pH of the various portions portions of the gastrointestinal tract. Orally administered immune serum completely protected the pigs from fluid loss and diarrhea. Parenterally administered serum did not protect against fluid loss into the intestinal lumen but diarrhea was not observed. The pH of the contents of the lumen of the cecum and colon was markedly elevated simultaneously with the accumulation of fluids and incompletely digested milk. The results of microscopic examination of tissues as well as other determinations did not reveal the mechanism of fluid loss nor the mechanism of protection afforded by orally administered immune serum. The results support the contention that continuous adequate levels of appropriate antibodies in the lumen of the intestinal tract aŕe a significant deterrant to the establishment of colibacillosis in baby pigs.

Animals↗

Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with intramuscular immune serum globulin. A randomized controlled trial.

OBJECTIVE: To estimate the risk of sexual transmission of hepatitis C and to assess the value of prophylaxis with periodic intramuscular immune serum globulin administration. METHODS: Of 1102 steady heterosexual partners of patients with antibodies to the hepatitis C virus (HCV), 899 were enrolled in a single-blind, randomized, controlled trial. All the partners tested negative for antibodies to HCV and had normal baseline serum aminotransferase concentrations. The partners were assigned to receive 4 mL of 16% polyvalent immune serum globulin prepared from unscreened donors every 2 months (n = 450) or a placebo (n = 449). Tests for HCV infection were performed every 4 months. RESULTS: Eight hundred eighty-four partners completed the study. Seven partners became infected with HCV: 6 in the control group (incidence density, 12.00 per 1000 person-years; 95% confidence interval, 3.0 21.61) and 1 in the immune serum globulin group (incidence density, 1.98 per 1000 person-years; 95% confidence interval, 0-5.86). The risk of infection was significantly higher for partners in the control group (P = .03): for each year approximately 1% of the partners became infected. Sequence homology studies strongly suggest the sexual transmission of HCV. All immune serum globulin lots used had high enzyme-linked immunosorbent assay titers of neutralizing antibodies to HCV envelope glycoproteins and high neutralization titers in the neutralization of binding assay. CONCLUSIONS: Hepatitis C can be sexually transmitted. Immune serum globulin prepared from unscreened donors significantly reduced the risk. The treatment was safe and well tolerated. Because only immune serum globulin from unscreened donors (and not from those screened for HCV) contain anti-HCV neutralizing antibodies, hyperimmune anti-HCV immune serum globulin should be prepared from blood testing positive for antibodies to HCV, which is currently discarded.

Adult↗