Hyperimmune Globulin Research Articles

Syncytium-inhibiting and neutralizing activity in maternal sera fail to prevent vertical transmission of human immunodeficiency virus type 1.

To measure the prevalence and titers of syncytium-inhibiting (SI) and neutralizing (Nt) antibodies to HIV-1 in mothers' blood close to the time of delivery and to correlate such findings with the infection status of their offspring. We analyzed serum specimens from a convenience sample of 22 HIV-infected mothers. The HIV-1 infection status of their children was determined. Forty-five percent of the women transmitted and 55% did not transmit infection to their offspring. Cord blood samples from offspring of the mothers were also studied. We measured maternal SI antibody titers against cells infected with HIV-1/SB, a strain isolated from a transmitting mother in New Haven, as well as cells infected with the more prevalent MN strain of HIV-1. We compared SI antibody titers to the SB strain in 11 matched maternal and cord blood samples. Nt antibody titers to HIV-1/SB were also measured in 20 maternal sera. Using the SB and MN strains of HIV-1, we found no difference in the prevalence or titer of SI antibody in the sera of transmitting and nontransmitting mothers. Only 35% of samples were concordant for presence or absence of SI antibody to the two strains. Furthermore the presence or absence of SI antibody in cord blood did not correlate with virus transmission. Both the frequency and titer of Nt antibody to HIV-1/SB were higher in the sera of mothers who transmitted infection when compared to those who did not. Only one-half of maternal blood samples were concordant for either the presence or absence of SI and Nt antibodies. We could not demonstrate a correlation between the presence of two types of functional antibodies (i.e. SI and Nt) to HIV-1 in the sera of pregnant women and vertical transmission. Efforts to induce or to increase such antibodies in infected mothers by immunization with vaccines or hyperimmune globulins may not alter the risk of vertical transmission.

Safety and immunogenicity of a tetravalent group B streptococcal polysaccharide vaccine in healthy adults

Proposed strategies for prevention of neonatal group B streptococcal (GBS) infection have included active immunization of pregnant women and passive immunization of high-risk infants with hyperimmune GBS globulin derived from vaccinated plasma donors. To explore the feasibility of a program for generating hyperimmune GBS globulin, we evaluated the safety and immunogenicity of a candidate multivalent GBS vaccine containing purified polysaccharide from types Ia, Ib, II, and III among subjects most likely to develop an immune response following vaccination, i.e. those with pre-existing antibody to GBS. Thirty volunteers prescreened for serum antibody to type III GBS were immunized with a single subcutaneous injection of vaccine containing either 10, 25, or 50 μg of each polysaccharide type (Group 1). An additional ten volunteers prescreened for antibody to type Ia were vaccinated with the 50 μg dose (Group 2). Vaccination was generally well tolerated with minor reactions occurring in 27% of subjects. Using a quantitative enzyme-linked immunosorbent assay (ELISA), the seroconversion rates (≥fourfold rise) and geometric mean antibody concentration (GMC in μg IgG ml −1) 6 weeks after vaccination in Group 1 to type Ia, II, and III were 33% (GMC 5.2), 17% (GMC 3.6), and 70% (GMC 43.4), respectively. Quantitative titers were not available for type Ib, but a fourfold rise in ELISA units was seen in 13% of subjects. In Group 2, seroconversion rates to type Ia and III were 90% (GMC 73.4) and 40% (GMC 22.2), respectively. No significant dose-response effect was detected. Combined analysis of Groups 1 and 2 demonstrated that subjects with prevaccination antibody concentrations >2 μg IgG ml −1 had significantly higher type-specific antibody concentrations following vaccination compared with subjects possessing lower levels of antibody before immunization. We conclude that our tetravalent GBS polysaccharide vaccine is safe but only modestly immunogenic in healthy seropositive adults. More potent vaccines will be required for public health use.

Protection by intratracheal immune globulins against Pseudomanas aeruginosa pneumonia in mice

A model for acute Pseudomonas pneumonia was established in mice with a mucoid, cystic fibrosis derived strain. Protection from pneumonia was achieved by intratracheal administration of hyperimmune globulins. The fate of intratracheal antibody was determined from lung lavage fluids and serum by a dot-ELISA test. Total and differential cellular changes in the lung were observed after immune globulin administration. Opsonophagocytosis assays with alveolar macrophages and PMNs elicited into the lungs showed that complement did not affect the bactericidal activities of either phagocyte. Conclusion: In mice, intratracheal administration of immune globulins against P. aeruginosa provided effective protection against acute pneumonia. The immediate availability of immune globulins in the lungs, and phagocytes are critical factors for clearance of the infecting dose of bacteria.

Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections.

Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants and young children. RSV causes especially severe disease in the prematurely born or those with chronic cardiopulmonary diseases. Elderly persons and those with T-cell deficiencies, such as bone marrow transplant recipients, are also at high risk for serious lower respiratory tract infections. To date, prevention of RSV infections by vaccination has proven elusive and no preventive drugs exist. Studies in animals and humans have shown that the lower respiratory tract can be protected from RSV infection by sufficient circulating RSV neutralizing antibody levels. Recently, an RSV hyperimmune immune globulin (RSVIG) was developed and tested for the prevention of RSV infections or reduction of disease severity. Passive immunization of high-risk children with RSVIG during the respiratory disease season effected significant reductions in RSV infections, hospitalizations, days of hospitalization, intensive care unit admissions, days in the intensive care unit, and ribavirin use. Studies in cotton rats and owl monkeys show that RSV infections can also be treated with inhalation of immune globulin at doses substantially smaller than required for parenteral treatment. Therapeutic trials of parenteral RSVIG have been completed and are pending analysis. The use of polyclonal, hyperimmune globulins and perhaps human monoclonal antibodies provides an additional approach to the prevention and perhaps the treatment of certain viral lower respiratory tract infections such as those caused by RSV.

Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections.

Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants and young children. RSV causes especially severe disease in the prematurely born or those with chronic cardiopulmonary diseases. Elderly persons and those with T-cell deficiencies, such as bone marrow transplant recipients, are also at high risk for serious lower respiratory tract infections. To date, prevention of RSV infections by vaccination has proven elusive and no preventive drugs exist. Studies in animals and humans have shown that the lower respiratory tract can be protected from RSV infection by sufficient circulating RSV neutralizing antibody levels. Recently, an RSV hyperimmune immune globulin (RSVIG) was developed and tested for the prevention of RSV infections or reduction of disease severity. Passive immunization of high-risk children with RSVIG during the respiratory disease season effected significant reductions in RSV infections, hospitalizations, days of hospitalization, intensive care unit admissions, days in the intensive care unit, and ribavirin use. Studies in cotton rats and owl monkeys show that RSV infections can also be treated with inhalation of immune globulin at doses substantially smaller than required for parenteral treatment. Therapeutic trials of parenteral RSVIG have been completed and are pending analysis. The use of polyclonal, hyperimmune globulins and perhaps human monoclonal antibodies provides an additional approach to the prevention and perhaps the treatment of certain viral lower respiratory tract infections such as those caused by RSV.

Recurrent Fulminant Liver Failure Caused by Hepatitis B Virus After Liver Transplantation

We report a 44-year-old man who received a liver graft because of fulminant liver failure due to hepatitis B virus. Nine months later a new episode of acute hepatitis B followed a fulminant course and led to another transplantation. The patient died due to invasive aspergillosis and multiorgan failure 3 weeks after the second transplant. This case reveals that hepatitis B virus reinfection may also occur after transplantation in patients with fulminant hepatitis B and under immunosuppression circumstances. Although immunoprophylaxis with hepatitis B hyperimmune globulin may prevent hepatitis B reinfection, it does not guarantee complete protection even in patients presumed to have low risk of reinfection. Finally, this case confirms the high risk of fungal infections in patients with fulminant liver failure and the need to establish early antifungal therapy.

Polysaccharide capsule-mediated resistance to opsonophagocytosis in Klebsiella pneumoniae.

The polysaccharide capsule of Klebsiella pneumoniae is an important virulence factor that confers resistance to phagocytosis. The treatment of encapsulated bacteria with salicylate to inhibit capsule expression was found to enhance the phagocytosis of encapsulated bacteria by human neutrophils only in the presence of cell surface-specific antibodies. Both type-specific rabbit antisera and anticapsular human hyperimmune globulin were employed as opsonins. Salicylate significantly enhanced phagocytosis with homologous, but not heterologous, whole-cell antisera. Antisera, diluted 1:40, no longer opsonized fully encapsulated bacteria but promoted the uptake of multiple salicylate-treated bacteria in > 90% of neutrophils. Salicylate (0.25 to 1.0 mM) also enhanced opsonization with globulin against homologous bacteria. Higher salicylate levels (1 to 2.5 mM) enhanced the opsonization of heterologous serotypes with human globulin. The nature of antibody attachment to encapsulated bacteria was determined by immunofluorescence. Even after the addition of purified capsular polysaccharide to prevent phagocytosis, K-specific antibodies attached in large amounts to bacteria. K-specific antibodies reacted with antigens throughout the capsule and showed a predilection for a denser inner layer of the capsule, indicating that many of the K-specific antibodies may be masked underneath the capsule surface. K-specific antibodies can also be rendered nonfunctional by soluble, cell-free capsular antigen. In culture, large quantities of soluble capsular polysaccharide extrude from bacteria after overnight growth. The reduction in capsule expression caused by salicylate largely affected the soluble, cell-free fraction. Purified capsular polysaccharide was shown to retard the opsonophagocytosis of salicylate-treated bacteria in a concentration-dependent manner. However, extensive washing of encapsulated bacteria to remove loosely attached capsular material did not significantly enhance opsonophagocytosis. In conclusion, cell-free capsule and cell-associated capsule are antiphagocytic; both act to neutralize K-specific antibodies by binding or concealment. Salicylate-mediated inhibition of capsule expression, particularly of the cell-free fraction, improved K-specific opsonization dramatically.

Immune-based interventions in perinatal human immunodeficiency virus infection

Essentially all new cases of human immunodeficiency virus (HIV) infection in infants and young children occur as a consequence of exposure to HIV either in utero, intrapartum or postpartum during breast feeding. Currently it is estimated that the majority of vertical transmission of HIV occurs at or near the time of birth. Based on what is known about the biology of perinatal HIV transmission, the HIV burden of the mother, effectiveness of her immune response and that of her fetus/infant and the integrity of the placental "barrier" are likely to play important roles in this process. The role of impaired immunologic control of HIV is gaining recognition as a potential key element in the pathophysiology of perinatal HIV transmission. In most studies to date, advanced maternal disease and low CD4 lymphocyte count have been associated with increased risk of vertical HIV transmission. In addition some studies have indicated that low maternal titers of antibodies to certain V3 loop epitopes may have a similar effect on vertical transmission. Cellular immune responses, which are known to play an important role in host defense against HIV, appear to be impaired in infants after exposure to HIV, especially those responses involving the development of cytotoxic lymphocytes. Mounting evidence suggests that enhancement of humoral and/or cellular immune responses in pregnant women and exposed infants is a logical and potentially feasible approach to interruption of perinatal transmission (an approach similar to that utilized for perinatally acquired hepatitis B virus infection). Studies are now in progress to assess HIV hyperimmune globulin and envelope HIV vaccines in pregnant woman and HIV-exposed infants.

Immunoglobulin Prophylaxis against Human T Cell Lymphotropic Virus Type II in Rabbits

Hyperimmune globulins, I-IgG and II-IgG, prepared from healthy persons seropositive for human T cell lymphotropic virus (HTLV) types I and II, respectively, were tested for their prophylactic effect against HTLV-II infection in rabbits. Three groups (A, B, and C) of 3 female rabbits each were used. Group A rabbits were inoculated intravenously with HTLV-II-carrying rabbit lymphoid cell line RII. Group B and C rabbits were immunized, respectively, with II-IgG and I-IgG and challenged with RII cells 24 h later. All group A and C rabbits seroconverted for HTLV-II after 2 weeks, but all group B rabbits were protected from HTLV-II infection. Gene amplification by polymerase chain reaction revealed the presence of HTLV-II provirus sequences in all group A and C rabbits but in none of the group B rabbits. These findings indicate that passive immunization with II-IgG is effective in preventing HTLV-II infection and that there is no cross-neutralization between HTLV-I and -II.

Use of immune globulin to prevent symptomatic cytomegalovirus disease in transplant recipients ‐ A meta‐analysis

The objective of this meta‐analysis was to review the evidence for the use of immune globulin in the prevention of symptomatic cytomegalovirus (CMV) disease in transplant recipients. A computerized search of Medline from 1980 to October 1991 was conducted using the textword “cytomegalo:” and the subheading “prevention and control” for studies in all languages. Reference lists, a manual search of relevant literature and communication with internationally recognized experts were used to locate additional studies. Of the studies identified, 18 met the inclusion criteria (population: transplant recipients; intervention: immune globulin; outcome: symptomatic cytomegalovirus disease; study design: randomized controlled trial). The meta‐analysis of the 18 studies showed a reduction in the incidence of symptomatic CMV disease in the group receiving immune globulin as compared to the untreated group. The common odds ratio was 0.58 (95% C.I. 0.42 to 0.77). Analyses of combining trials by subgroups of polyvalent immune globulin, hyperimmune globulin, bone marrow recipients and solid organ recipients resulted in common odds ratios comparable to the overall common odds ratio. Common odds ratios for the trials reporting cytomegalovirus interstitial pneumonia, cytomegalovirus death, overall death and graft loss ranged from 0.47 to 0.69. Common odds ratios for the effect of immune globulin prophylaxis analyzed by pre‐transplant patient/donor cytomegalovirus antibody status ranged from 0.32 to 0.50. In conclusion, the use of immune globulin as passive immunization for the prevention of symptomatic cytomegalovirus disease in the transplant population is supported by this meta‐analysis. The response is similar in both bone marrow and solid organ transplant recipients. There appears to be no significant clinical advantage in the use of hyperimmune globulin over polyvalent immune globulin.

VIRAL PROPHYLAXIS IN COMBINED PANCREAS-KIDNEY TRANSPLANT RECIPIENTS

The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.

VIRAL PROPHYLAXIS IN COMBINED PANCREAS-KIDNEY TRANSPLANT RECIPIENTS

The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immuno-suppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (FVTG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclo-vir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard FVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100–150 mg/kg) plus 2 weeks of IV ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommend that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.

Bacterial polysaccharide immune globulin for prophylaxis of acute otitis media in high-risk children

We evaluated the prevention of recurrences of acute otitis media (AOM) by bacterial polysaccharide immune globulin (BPIG), a hyperimmune human immune globulin prepared by immunizing donors with bacterial polysaccharide vaccines. We used a randomized, stratified, double-blind, placebo-controlled design. Children < or = 24 months of age with 1 to 3 prior episodes of AOM received BPIG, 0.5 ml/kg, or saline placebo intramuscularly at entry and 30 days later. During the 120-day follow-up period, AOM was diagnosed by using clinical criteria and was confirmed with tympanocentesis and culture of the middle ear exudates. Eighty-eight episodes of AOM were observed in 76 patients who completed the study. The incidence of AOM during the entire 120-day study period was similar in BPIG and placebo recipients. Pneumococcal AOM was significantly less frequent in BPIG recipients (0.21 episode per patient) than in placebo recipients (0.45 episode per patient; p = 0.05). Time spent free of AOM was significantly prolonged in recipients of BPIG, in comparison with placebo recipients (51 vs 35 days; p = 0.034). This study demonstrated that circulating antibody, even without stimulation of specific local immunity, may prevent infection of the middle ear. The use of immune globulin preparations for longer periods or at a higher dosage might decrease the incidence of recurrent AOM in otitis-prone children, and deserves further evaluation.

Comparison of group B streptococcal hyperimmune globulin and standard intravenously administered immune globulin in neonates

Standard intravenously administered immune globulin (IVIG) contains varying amounts of group B streptococcus (GBS) antibody. A GBS hyperimmune IVIG was produced by immunizing plasma donors. The GBS type-specific opsonic activity was > or = 90% in the hyperimmune IVIG at a 1280 dilution-1 versus at a 10 dilution-1 in standard IVIG. Suckling rat survival after GBS type-specific infection was 100% when the rats were treated with hyperimmune IVIG versus < or = 20% with standard IVIG. To evaluate the effect of this product on GBS antibody levels and clinical toxic effects, we randomly administered either GBS hyperimmune IVIG, 500, 250, or 100 mg/kg, or standard IVIG, 500 mg/kg, to 20 neonates with suspected sepsis. No adverse effects were observed. Total and subclass serum IgG levels reflected only the dose; serum GBS type-specific IgG and opsonic activity reflected both the product and dose of IVIG administered. Standard IVIG did not significantly increase serum GBS type-specific IgG, whereas hyperimmune IVIG, 500 mg/kg, produced a fourfold rise for > 6 weeks; more variable increases were observed after 250 and 100 mg/kg doses were given. Serum GBS type-specific opsonic activity correlated with serum GBS type-specific IgG levels (R2 = 0.74; p < 0.0001). Further studies of this or similar products will be necessary to determine whether GBS type-specific antibody improves the outcome of GBS-infected neonates.

Humoral immune response to human cytomegalovirus infection: diagnostic potential of immunoglobulin class and IgG subclass antibody response to human cytomegalovirus early and late antigens.

For the development of effective prophylaxis (hyperimmune globulins) and improvement of serological testing for human cytomegalovirus (HCMV) infection in immunocompromised patients it is essential to characterize the viral encoded proteins and the humoral immune response in terms of neutralizing antibodies and immunoglobulin class and IgG subclass reactivity to "early" and "late" HCMV proteins. The major neutralizing epitopes have been identified and screening of donor sera for neutralizing antibody by either conventional neutralization assays or enzyme-linked immunosorbent assay using recombinant antigens may help to improve the efficacy of hyperimmune globulin prophylaxis. The humoral response to individual HCMV proteins has been thoroughly investigated in immunocompromised patients. Antibodies against HCMV induced "early" antigens are not exclusively associated with active infection but may indicate an elevated risk for cytomegalic inclusion disease in immunocompromised patients. With a sensitive western blot technique. IgM and IgA antibodies against HCMV "late" proteins can be detected in sera from healthy seropositive individuals. Serum samples from subjects suffering from cytomegalic inclusion disease show significantly larger broader immune responses compared with healthy HCMV antibody carriers. Promising results using recombinant antigens corresponding to immunodominant epitopes for the detection of HCMV specific antibodies have been published.

Early detection of primary cytomegalovirus infection after heart and kidney transplantation and the influence of hyperimmune globulin prophylaxis

A randomized study of prophylaxis with hyperimmune globulin (HIg) was performed in 28 cytomegalovirus (CMV)-seronegative heart and kidney recipients with CMV-seropositive donors who were extensively monitored for active CMV infection and CMV disease. Detection of CMV antigen in peripheral blood granulocytes (antigenemia) was the first sign of primary CMV infection, generally occurring several weeks before IgM or IgG anti-CMV antibodies were detected and before positive cultures appeared. A correlation was found between rejection treatment with OKT3 or ATG, severity of CMV disease, and graft loss. Rejection treatment had no influence on incidence of CMV transmission. Primary CMV infection occurred most often in older patients with older donors. No beneficial effects were seen with HIg prophylaxis, which was administered from week 1 until week 7 after transplantation. Incidence of primary CMV infection was equal in both groups (50%) and no influence on the severity of primary CMV infection was seen. The only effect that was seen was on the time from transplantation to detection of active CMV infection, which was prolonged by HIg prophylaxis.

Prophylaxis of Cytomegalovirus in Renal Transplant Recipients

The incidence and outcome of cytomegalovirus (CMV) infection and disease is compared in renal transplant recipients in relation lo the use of prophylaxis wiU1 high titre anti‐CMV immunoglobulin. Seventy‐three CMV‐negative recipients (R‐) who received kidneys from CMV‐posilive donors (D+) were given prophylactic CMV hyperimmune globulin inlravenously al three‐week intervals lo six monilis. They also received Lhree months of oral low dose acyclovir as did the remaining 288 patients who did nol receive hyperimmune globulin. There was a low incidence of CMV disease which did not differ between groups (D+R‐, 10%: D+R+, 5 .5%, D‐ R+, 7%: D‐ R‐, 0.8%). The major risk factor was the use of OKT3 to treat rejection. CMV disease was seen in 22% of this group (11 of 50) . compared with only 2% (seven of 311) of those not requiring OKT3. There was only one CMV‐related death. but palients with CMV disease had a reduced graft survival rate (62% versus 90%). CMV hyperimmune globulin added lo acyclovir appears to reduce the incidence of CMV disease in high risk renal recipients (D+R‐) in the lower risk groups.

Early detection of primary cytomegalovirus infection after heart and kidney transplantation and the influence of hyperimmune globulin prophylaxis

Abstract. A randomized study of prophylaxis with hyperimmune globulin (HIg) was performed in 28 cytomegalovirus (CMV)-seronegative heart and kidney recipients with CMV-seropositive donors who were extensively monitored for active CMV infection and CMV disease. Detection of CMV antigen in peripheral blood granulocytes (antigenemia) was the first sign of primary CMV infection, generally occurring several weeks before IgM or IgG anti-CMV antibodies were detected and before positive cultures appeared. A correlation was found between rejection treatment with OKT3 or ATG, severity of CMV disease, and graft loss. Rejection treatment had no influence on incidence of CMV transmission. Primary CMV infection occurred most often in older patients with older donors. No beneficial effects were seen with HIg prophylaxis, which was administered from week 1 until week 7 after transplantation. Incidence of primary CMV infection was equal in both groups (50 %) and no influence on the severity of primary CMV infection was seen. The only effect that was seen was on the time from transplantation to detection of active CMV infection, which was prolonged by HIg prophylaxis.

Low frequency of transfusion-related disease in children undergoing peripheral blood stem cell autografts.

Forty-nine children who received peripheral blood stem cell autografts (PBSCT) were observed for the development of transfusion-related disease (TRD), including cytomegalovirus (CMV) disease, alloimmunization, and graft-versus-host disease (GVHD). Cytoreductive regimens did not include total body irradiation. A comprehensive prophylactic strategy including alkylated hyperimmune CMV globulin and filtered, nonirradiated, leukocyte-poor blood products was applied. Two patients showed temporary refractoriness to platelet transfusion, but none suffered from symptomatic CMV infection or GVHD. Thus, under these conditions the incidence of TRD appears to be low in children undergoing PBSCT.

Prevention of Haemophilus influenzae type b disease

Haemophilus influenzae type b (Hib) is the leading cause of meningitis in children < 5 years of age. The majority of cases of Hib occur in infants < 2 years of age. Until recently the only vaccine available against this disease contained the pure polysaccharide (PRP) of Hib (Hib-PRP vaccine). The Hib-PRP vaccine was demonstrated to be efficacious in infants >18 months of age but not below that age. This product was licensed for routine use in the USA for children aged 24 months or more. Recently a hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIg) was prepared by immunizing adult donors with Hib-PRP, meningococcal and pneumococcal vaccines, BPIg has been demonstrated to prevent Hib infections when it is administered to infants at 4-month intervals. However, BPIg has not been licensed for routine use in the USA. A number of new Hib conjugate vaccines have also been developed in the last few years by convalently linking the Hib-PRP to different carrier proteins. Four different Hib conjugate vaccines have undergone clinical trials in the USA. Two of these vaccines, HbOC (Hib capsular oligosaccharide linked to CRM197) and Hib-OMPC (Hib capsular polysaccharide linked to Neisseria meningitidis outer membrane protein complex) have been demonstrated to protect infants aged 2 months or more from Hib disease. Both HbOC and Hib-OMPC are currently licensed for routine use in the USA. The widespread use of these vaccines should have a substantial impact in reducing morbidity and mortality from Hib disease.