Baseline Titers Research Articles

Renal Transplantation in Patients With Positive Lymphocytotoxicity Crossmatches: One Center’s Experience

Sensitization to human leukocyte antigens remains an important barrier to successful renal transplantation. Herein we describe our center's experience with a plasmapheresis-based desensitization protocol for highly sensitized patients. Twenty-nine patients had a positive T-cell or positive B-cell lymphocytotoxicity crossmatch against their donors. In some cases, baseline crossmatches were of high titer (e.g., 11 had baseline titers > or =1:32). Twenty-eight of 29 patients were rendered T-cell crossmatch negative and B-cell crossmatch negative/low positive and transplanted. None had hyperacute rejection but 11 (39%) had acute antibody mediated rejection. Median follow-up is 22 months: 25 of the 28 (89%) of allografts are still functioning with mean plasma creatinine 1.5 mg/dL. There was one death because of the transplant or immunsuppression, one case of cytomegalovirus disease and no cases of lymphoproliferative disease. This series provides further evidence of the high efficacy of plasmapheresis-based desensitization protocols. Even patients with high baseline crossmatch titers can be successfully desensitized and transplanted. Short- and medium-term outcomes are encouraging but longer-term data are needed.

Seroprevalence of anti Vi antibodies and immunogenicity of Typhim Vi vaccine in children

This prospective study was carried out on 250 children between 6 months to 5 years of age to determine seroprevalence of anti Vi antibodies and to measure seroresponse and percent seroconversion to TyphimVi polysaccharide vaccine in children 2-5 years of age. Fifty children each were enrolled between 6 to12 months of age (Group A), between 1- 2 years of age(Group B), between 2-3 years of age(Group C), between 3-4 years of age (Group D) and between 4-5 years of age (Group E). Anti- Vi antibody baseline titres were determined in all children. Children in Groups C to E were vaccinated with Typhim Vi vaccine. Baseline and postvaccination antibody titres were determined by ELISA. Test serum which had antibody levels >1 µg/ml were scored as seropositive. Of 250 children, 3 had base line anti-Vi antibodies >1µg/ml. Following immunization overall seroconversion rate was 77.5% with 65.3%, 78.2% and 88% children showing seroconversion in Groups C, D and E respectively. Seroconversion was significantly more in Group E children compared to Group C (p=0.0148). There were no significant adverse reactions following vaccination. The study highlights very low prevalence of baseline anti Vi antibodies in children between 6 months and less than 5 years of age and shows high immunogenicity and safety of Typhim Vi polysaccharide vaccine in children 2- 5 years of age.

Social support is positively associated with the immunoglobulin M response to vaccination with pneumococcal polysaccharides

Evidence shows that psychosocial factors are associated with immunoglobulin G response to medical vaccinations. As yet, there are no reports of whether the earlier immunoglobulin M response is similarly susceptible. This study examined the association between psychological stress, social support and the immunoglobulin M response to vaccination with pneumococcal capsular polysaccharides. Stressful life events in the previous year and customary social support were measured by standard questionnaires at baseline in 74 healthy students (41 females). The response to five common pneumococcal serotypes was assessed at baseline and 5 days following vaccination. Social support, particularly tangible social support, was positively associated with the antibody response to two of five serotypes, after controlling for baseline titre. These associations survived adjustment for demographics and health behaviours. There was no association between life events stress and immunoglobulin M response. It appears that psychosocial factors affect both the immunoglobulin M and immunoglobulin G responses to vaccination.

An observational study of sucrose-formulated recombinant factor VIII for Japanese patients with haemophilia A

The safety and efficacy of sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate FS) under usual clinical practice were evaluated for 12 months in an observational, postmarketing surveillance study conducted at 214 treatment centres throughout Japan. The study included 631 patients with haemophilia A, 80% of whom had severe or moderately-severe disease (< or = 2% FVIII:C). Most patients (n = 477; 75.6%) had >100 prior exposure days (EDs), but the study also included 62 (9.8%) patients with <20 EDs who were at high risk for inhibitor development. A total of 71,240 infusions were administered during the observation (mean, 113 +/- 108 per patient). Physicians rated efficacy and tolerability of rFVIII-FS as "very good" or "good" in >99% of patients. FVIII inhibitors were observed in seven patients (5 de novo; 1 persistent/fluctuating; 1 recurrent). The overall de novo inhibitor incidence was 0.8% (5/631; or 5/599 among the subgroup of patients with negative baseline titre and no known inhibitor history). De novo cases represented 3.2% (2/62) of patients with <20 EDs at enrollment (2/57 in the no inhibitor subgroup) and 0.2% (1/477) of patients pretreated with >100 EDs (1/452 in the no inhibitor subgroup) at enrollment. The results of this large observational study demonstrate that rFVIII-FS is both safe and efficacious as used in the usual clinical setting for the treatment of Japanese patients with mild to severe haemophilia A. This study supports the efficacy of rFVIII-FS with an incidence of inhibitor formation no greater than in a comparable European study or previous phase III clinical studies.

Seasonal glucocorticoid responses to capture in wild free-living mammals

We determined baseline and capture-induced glucocorticoid concentrations during two different seasons in three species of wild free-living rodents: brown lemmings (Lemmus trimucronatus), golden-mantled ground squirrels (Spermophilus saturatus), and yellow-pine chipmunks (Tamias amoenus). Initial blood samples were obtained within 3 min of capture, so that initial glucocorticoid levels reflect baseline titers of undisturbed animals. Animals were held for an additional 30 min, when a second blood sample was taken to measure stress-induced glucocorticoid titers. The primary glucocorticoid differed in each species. Lemmings secreted extremely large amounts of corticosterone (as high as 8,000 ng/ml). These high concentrations were accompanied by high corticosterone-binding globulin capacity and resistance to negative feedback. Squirrels and chipmunks secreted a mixture of cortisol and corticosterone (10-400 ng/ml). In males of all three species and female squirrels and chipmunks, glucocorticoid levels were significantly elevated 30 min after capture. Baseline and 30-min glucocorticoid levels differed seasonally in each species. Levels were higher during summer (with no snow cover) than in spring (with approximately 60% snow cover) in female lemmings, higher during breeding than before hibernation in squirrels, and higher postreproductively than during breeding in chipmunks. Together, these data indicate that glucocorticoid responses to stress in these free-living species are similar to those in laboratory species, but the magnitude of the response appears to depend on life-history features specific to each species.

Baseline Widal titres in healthy children

To determine the baseline Widal titres in apparently healthy children in Davangere. Cross-sectional study was done on 250 children. Widal titers were found using tube agglutination test. Out of 250,64.2% had a titre of less than 1:20,22.4% had a titre equal to 1:20,9.6% had a titre of 1:40 and 3.6% had a titre of 1:80 to 'O' antigen and 67.2% had a titre of less than 1:20, 21.2% had a titre equal to 1:20, 8% had a titre of 1:40 and 3.6% had a titre of 1:80 to 'H' antigen of S. enterica subsp. enterica ser. Typhi. No children in age group 6 months-2 years had a titre of 1:80 to either antigen. All children in this age group had a titre of less than 1:20 to AH antigen and older children had a titre upto 1:40 dilution. Baseline titres for either S. enterica subsp. enterica ser. Typhi antigen in 6 month-2 year was 1:40 and older children was 1:80. Baseline titres for H antigen of S. enterica subsp. enterica ser. Paratyphi A in 6 month-2 year was less than 1:20 and for older children was 1:40 dilution.

Immunogenicity, Reactogenicity, and Safety of a P1.7b,4 Strain-Specific Serogroup B Meningococcal Vaccine Given to Preteens

New Zealand (NZ) has experienced a Neisseria meningitidis serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (n = 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (n = 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of <1:4 required titers of >/=1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children.

Evaluation of an indirect immunofluorescence assay for strongyloidiasis as a tool for diagnosis and follow-up.

The diagnostic accuracy of an indirect immunofluorescence antibody test (IFAT) for Strongyloides stercoralis at different serum antibody titers was evaluated. To assess diagnostic sensitivity, sera from 156 patients with known strongyloidiasis were collected. Negative control sera were obtained from a composite group of 427 subjects (blood donors and hospitalized patients). With an area under the receiver-operating characteristic plot of 0.98, the IFAT showed a high level of diagnostic accuracy for strongyloidiasis. An antibody titer of > or = 1:20, with 97% sensitivity and 98% specificity, was identified as the diagnostic threshold with the best overall performance. Cross-reactions were evaluated with 41 additional samples from patients with other known helminth infections, and the IFAT detected low-titer positivity in only one subject with filariasis. A positive IFAT result at an antibody dilution of > or = 1:80 was virtually 100% specific, with 71% sensitivity. To test the usefulness of the IFAT as a monitoring tool, the changes in specific-antibody titers after treatment in a group of 155 patients were evaluated. Seroreversion or a decrease in antibody titer of twofold or more was observed in 60% of the patients. Response to treatment was directly correlated to the initial antibody titer, and a baseline titer of > or = 1:80 was identified as the best predictor of response. In conclusion, a positive IFAT result at an antibody dilution of >/=1:20 is the optimal cutoff for screening. A titer of > or = 1:80, with virtually no false-positive result, is a reliable cutoff for a serological assessment of treatment efficacy and for inclusion in clinical trials.

ABO-Incompatible Kidney Transplantation with and without Splenectomy

The letter to the editor from Dr. Mitsuhata et al. raises interesting points with regard to the role of splenectomy in ABO-incompatible (ABOI) kidney transplants. The authors contend that the classification of ABOI kidney transplant recipients as “high risk” should not be made on the basis of baseline antibody titer. The association of humoral rejection with baseline antidonor blood group antibody titer in splenectomized ABOI recipients not undergoing posttransplant plasmapheresis has been reported by Shimmura et al., who found a 70% humoral rejection rate in patients with baseline titer ≥128 and 20% in those with titers ≤1:64 (1). These findings are similar to those of our report in which rejection occurred in 12% of patients with titers <1:64, while 83% of those with titers exceeding 1:64 rejected (2). Interestingly, Shimmura et al. have recently reported that posttransplant plasmapheresis to maintain a low titer in conjunction with splenectomy is effective in preventing humoral rejection in ABOI recipients with very high baseline titers (3). In their letter, Mitsuhata et al. refer to their Brief Communication describing their use of mycophenolate mofetil during four weeks preceding ABOI transplantation in 18 patients compared to 18 patients who did not receive pretransplant mycophenolate mofetil (4). In their report, all patients underwent antibody lowering therapy with plasmapheresis or plasma exchange. No comment was made as to whether or not recipients underwent splenectomy, although their current letter to the editor implies that they did. They report improved allograft survival six months after transplant in the pretreated group, although the humoral rejection rate was comparable. The causes for allograft loss in the pretreatment group were not reported, nor were baseline antidonor blood group antibody titers. The authors indicate that on the day of transplantation antidonor blood group antibody titers ranging from 1–128, although not specifically reported. Given our admittedly smaller experience in ABOI kidney transplantation, we would be very reluctant to proceed to transplantation at the time the recipient's titer exceeded 1:16, and our practice is to continue to perform plasmapheresis until achieving a titer ≤1:8 on the day of transplantation. An important point is that the antibody titer depends strongly on the method used to measure it. It is possible that the antibody measurement technique used by Mitsuhata et al. differs from the technique reported in our investigation. The authors present their opinion that the benefits of transplantation without splenectomy are outweighed by the psychological, physical, and economic burden posed by posttransplant plasmapheresis and/or anti-CD20 antibody therapy. Our opinion is that with aggressive posttransplant antibody monitoring and therapy to maintain low titer during the first two weeks after transplantation, humoral rejection is an unusual complication in the large majority of ABOI kidney transplants. We also feel that the life long advantage of avoiding splenectomy exceeds the disadvantage of posttransplant therapy during the first one to two weeks after transplantation. Finally, the authors refer to the important fact that other potentially injurious antibodies with donor reactivity may also complicate ABOI transplantation, similar to ABO compatible transplants, and we agree. James Gloor Department of Internal Medicine and Nephrology Mayo Clinic Rochester, MN Mark Stegall Division of Transplantation Surgery Mayo Clinic Rochester, MN

Quantitative Evaluation of Rotaviral Antigenemia in Children with Acute Rotaviral Diarrhea

Rotaviral antigen and RNA have recently been identified in the serum of patients with rotaviral gastroenteritis, but the roles they play in disease remains undetermined. Rotaviral antigen and RNA were quantified by enzyme-linked immunosorbant assay and by quantitative reverse-transcription polymerase chain reaction in stool and serum specimens from children with rotaviral diarrhea (n=102), children with nonrotaviral diarrhea (n=40), and nondiarrheal control children (n=30). Rotaviral antigenemia was detected in 64%, 3%, and 0% of the children with rotaviral diarrhea, the children with nonrotaviral diarrhea, and the nondiarrheal control children, respectively. The level of rotaviral antigen in serum was approximately 2x10(2) -fold lower than that in stool, and a moderate correlation was observed between the 2 levels. Rotaviral RNA was detected in 93% of the antigen-positive serum specimens. The median number of RNA copies in serum was approximately 1 x 10(5) -fold lower than that in stool, and no correlation was observed between the 2 levels. Serum levels of both antigen and RNA were inversely associated with baseline titers of rotaviral serum immunoglobulin G (P<.01). Antigenemia was also associated with G1 serotype. Rotaviral antigenemia and viremia were common in children with rotaviral diarrhea, but antigen and RNA levels in serum were substantially lower than those in stool. Antigenemia was associated with infection with G1 strains and with low baseline titers of rotaviral serum antibody.

Age-related variation in the adrenocortical response to stress in nestling white storks ( Ciconia ciconia) supports the developmental hypothesis

The post-natal development of the adrenocortical response to stress was investigated in European white storks. Sixty wild nestlings aged 24–59 days old were subjected to a standardized capture and restraint protocol, and the time-course pattern of the response to stress was assessed through determination of circulating corticosterone in blood samples collected at five fixed times during the 45-min period following capture. The time course of the response was best fit to a third-order function of handling time, and showed a strong effect of age. Although age did not affect baseline titers and all birds showed a positive post-capture increase in circulating corticosterone, age had a positive effect on the relative increase from baseline titer, the recorded time to reach maximum level, and the acute concentration after 10 min following capture and restraint. While young nestlings displayed very little response to capture, the response near fledging resembled the typical adrenocortical pattern widely reported in fully developed birds. Our results concur with those found in altricial and semi-altricial species, and suggest that non-precocial birds follow a similar mode of development of the hypothalamic–pituitary–adrenal (HPA) axis. The fact that HPA sensitivity to stress is functional suggests that young storks gradually develop emergency responses of adaptive value and are able to overcome acute perturbations in spite of their parental dependence, at least during the last two-thirds of post-natal development. According to the Developmental Hypothesis, such gradual changes would allow nestlings to respond to perturbations as a function of the specific behavioral and physiological abilities of their age. The potential sources of stress that nestlings have to face during development (i.e., weather conditions, dietary restrictions, and social competition) are discussed according to developmental changes in behavioral and physiological abilities.

Evaluation of immunogenicity and side effects of triple viral vaccine (MMR) in adults, given by two routes: subcutaneous and respiratory (aerosol)

Adult volunteers from two neighboring health centers were immunized with measles, mumps, rubella vaccine (MMR, Serum Institute of India Ltd.), either given by traditional injections or by an aerosol delivered to the respiratory tract. Baseline and one month post vaccination samples were taken and simultaneously assayed for all three antigens. Subjects were followed-up for temporally associated events after vaccination. The aerosol route was superior for measles, mumps and rubella when baseline titers were controlled for in multivariate analysis. Frequencies of post-vaccination events did not differ with statistical significance between the groups. Further evaluation of the aerosol route for MMR immunization appears warranted.

Acquired factor VIII inhibitors in non‐haemophilic patients: clinical experience of 15 cases

We retrospectively analysed 15 non-haemophilic patients with acquired factor VIII inhibitors seen in our regional haemophilia centre. The median age was 55 years (range: 21-80). About 70% of patients older than 50 were male, while all five patients younger than 50 were female. The most common underlying condition was pregnancy or postpartum status (20%). About 27% of cases had no identifiable underlying condition. About 27% of patients had medical conditions that were unlikely to be related to acquired inhibitors. The most frequent presenting symptom was spontaneous haemorrhage of soft tissues, skin or joints. Twelve of 13 (92.3%) evaluable patients achieved complete remission (CR) with prednisone alone and/or combined prednisone and cyclophosphamide, but their clinical courses were highly variable. The median time to response was 21.5 weeks (range: 2-176) and the median treatment duration was 9 months (range: 1.25-66). All six patients treated with prednisone initially, and then combined prednisone/cyclophosphamide if no response (NR) to prednisone within 3-4 months (three patients), achieved CR; while four of five patients treated initially with combined prednisone/cyclophosphamide had CR. Patients older than 50 years had a similar response rate, median time to response and median treatment duration as did patients younger than 50 years (83% vs. 100%; 21.5 vs. 32 weeks, and 8 vs 16.5 months, respectively). Furthermore, the differences in the median time to response and treatment duration for patients with high or low baseline or peak inhibitor titres were negligible. Only one patient died of a treatment-related pulmonary aspergillosis 18 months after an acquired inhibitor was diagnosed. None of these patients died of bleeding complications. In conclusion, our patients with acquired FVIII inhibitor had highly variable clinical courses and responses to steroid or immunosuppressive therapy. The inhibitors in the majority of patients resolved in less than 6 months although in two cases it persisted for longer than 1 year before resolving. Treatment with prednisone alone as first line, then combined prednisone with cyclophosphamide if NR to prednisone seemed equally effective when compared with using combined prednisone and cyclophosphamide initially. Further studies of newer therapeutic agents such as 2-chlorodeoxyadenosine (2-CDA) and rituximab are warranted for patients refractory to conventional immunosupressive therapy.

The distribution of anti-Salmonella antibodies in the sera of blood donors in Yaoundé, Cameroon

This cross-sectional study in late 1996 on a group of 230 consecutive blood donors in Yaoundé, Cameroon, found a baseline titre of 1:100 for antisalmonella O antibodies. The seroprevalence and baseline titre for antisalmonella H antibodies was much higher (1:400), suggesting that the H antibody is of limited diagnostic value in Cameroon.

A multicenter, randomized, controlled clinical trial of interferon alfacon-1 in comparison with lymphoblastoid interferon-alpha in patients with high-titer chronic hepatitis C virus infection

This multicenter, randomized, controlled study evaluated the efficacy and safety of interferon alfacon-1 (r-IFN-αcon1) compared with lymphoblastoid interferon-alpha (IFN-αn1) in patients with high-titer chronic hepatitis C virus (HCV) infection. Two hundred and seven patients were randomized to receive either 18 MIU (μg) r-IFN-αcon1 or 9 MIU IFN-αn1 daily for 2 weeks, followed by the administration of the study drugs three times weekly for 22 weeks. The primary endpoint was sustained virological response defined as the inability to detect serum HCV RNA at the end of the 24 week post-treatment observation period. In the intention-to-treat analysis, r-IFN-αcon1 produced a slightly but not significantly higher proportion of sustained virological response than IFN-αn1 (26.3 vs. 20.7% P=0.392). In patients with high baseline titer and genotype 1b, the proportion of sustained virological response was significantly higher in the r-IFN-αcon1 cohort, than the IFN-αn1 cohort (16.7 vs. 3.3%, P=0.017). The adverse events commonly reported were flu-like symptoms, anorexia, insomnia, and alopecia. Types and frequencies of the adverse events were similar in the two cohorts. The results of this study show that r-IFN-αcon1 is an effective and tolerable therapy in patients with chronic HCV with high viral titer. The results also indicate that 18 MIU r-IFN-αcon1 is superior in efficacy without additional toxicity to 9 MIU IFN-αn1 in high-titer chronic HCV patients, particularly with genotype 1b.

Safety and immunogenicity of intranasally administered inactivated trivalent virosome-formulated influenza vaccine containing Escherichia coli heat-labile toxin as a mucosal adjuvant.

A trivalent influenza virosome vaccine containing hemagglutinin and Escherichia coli heat-labile toxin (HLT) was administered intranasally to young adults and elderly subjects. Symptoms that followed immunization were mild and transient. A significant increase in serum hemagglutination inhibition (HI) antibody was noted for the 3 vaccine strains. There was no significant difference in postimmunization geometric mean titers or seroconversion rates between age groups. The percentage of subjects attaining protective HI titers (>/=40%) was comparable in both groups for the A/Bayern (P=.5) and B/Beijing (P=.3) strains but was higher among young adults (92.2%) versus elderly subjects (76.5%; P=.057) for the A/Wuhan strain. The proportion of subjects with nonprotective baseline titers who attained protective levels after immunization was similar in both age groups for the A/Bayern and B/Beijing components. For the A/Wuhan component, significantly (P=.017) more young adults achieved protective titers versus elderly subjects (85. 7% and 53.8%, respectively). Vaccination evoked a significant (P<. 005) increase in anti-HLT antibody titers.

Retreatment with higher dose interferon alpha in children with chronic hepatitis B infection.

More than 50% of children with chronic hepatitis B infection do not respond to interferon-alpha (IFN-alpha) treatment and are prone to have progressive liver disease. The best treatment modality is unknown in these children. The aim of this study was to evaluate the possible benefit of a second higher dose IFN-alpha therapy for children with chronic hepatitis B diseases who failed previous therapy. Twenty-four children with chronic hepatitis B infection who had not responded to previous IFN-alpha treatment were enrolled into the study. All were hepatitis B virus DNA- and hepatitis B e antigen-positive for >6 months after initial treatment. They received 10 megaunits (MU)/m2 of IFN-alpha 2a three times a week for 24 weeks. Liver function tests, hepatitis B virus markers and hepatitis B virus DNA were determined regularly during treatment and follow-up. A complete response was defined as clearance of both hepatitis B virus DNA and hepatitis B e antigen (HBeAg). At the end of therapy 8 (33.3%) patients cleared hepatitis B virus DNA and seroconverted to anti-HBeAg. Patients were followed for an average period of 12.2 +/- 4.7 months after retreatment. During follow-up an additional 4 patients cleared hepatitis B virus DNA and seroconverted to anti-HBe, whereas one seroconverted patient became HBeAg-positive again. Thus 11 patients (45.8%) had complete response at the end of the follow-up period. Alanine aminotransferase normalized in 11 responder patients and in 5 nonresponders. Positive predictive factors were low baseline titers of hepatitis B virus DNA and elevated transaminase values (> 100 IU/l). IFN-alpha retreatment with a higher dose may be an alternative modality for treatment of children with chronic hepatitis B infections who failed previous IFN-alpha, especially in those with favorable predictive factors.

Safety and characterization of the immune response engendered by two combined measles, mumps and rubella vaccines

We performed a randomized trial to compare the safety and immunogenicity of two combined measles, mumps and rubella vaccines in healthy children 14–24 months of age. Triviraten Berna ® Vaccine (Swiss Serum and Vaccine Institute), contains the Edmonston Zagreb 19 strain of measles virus, the Rubini mumps virus strain and the Wistar RA 27 3 rubella strain while MMR-Vax ® (Merck, Sharp & Dohme, West Point, PA) contains the Enders attenuated Edmonston measles strain, the Jeryl Lynn mumps strain and the Wistar RA 27 3 rubella strain. Immunization with Triviraten Berna ® was associated with a significantly lower incidence of swelling and redness at the injection site in addition to a reduced rate of fever compared with MMR-Vax. Seroconversion rates for the measles and rubella vaccine components were comparable in all tests used. However, seroconversion for the mumps vaccine component was test-dependent. Using an ELISA, the seroconversion rate following immunization with MMR-Vax was significantly ( P < 0.01) higher than for Triviraten Berna. In contrast, nearly identical rates were obtained using an indirect immunofluorescence test. Both vaccines were equally effective at engendering antibodies capable of neutralizing wild type mumps virus. Geometric mean ELISA antibody titers against measles and mumps virus were higher following immunization with MMR-Vax while that for rubella was higher after immunization with Triviraten Berna. A small number ( N = 13) of adolescents immunized either with MMR-Vax or Triviraten Berna were reimmunized with Triviraten Berna and various humoral and cellular response parameters to the measles and mumps vaccine components analyzed. While few subjects mounted a humoral antibody response to measles, most likely due to elevated baseline titers, there was a marked lymphoproliferative response. Anti-mumps virus ELISA antibody titers were higher both at baseline and after reimmunization in subjects who received MMR-Vax for primary immunization. However, there was no difference in either neutralizing titer or proliferative response in subjects primed with MMR-Vax or Triviraten Berna either before or after reimmunization.

Thyroid abnormalities in chronic viral hepatitis and their relationship to interferon alfa therapy.

The prevalence of antithyroid peroxidase antibodies (ATPO) and/or of thyroid dysfunction was studied in 422 patients with chronic viral hepatitis C, B, and D. Baseline results were compared with those during and 6 months after interferon alfa (IFN-alpha) therapy. The overall prevalence of ATPO among untreated patients was 14.1%, with no significant differences between chronic hepatitis C, B, or D, as well as between males and females. However, high ATPO titers (> or = 18 IU/mL) clustered significantly among females (8.7% vs. 3.4%; P = .022), especially those with chronic hepatitis C (11.2% vs. 3.6%; P = .036). Before treatment, 3.7% of the patients had thyroid dysfunction, mostly hypothyroidism (3.5%), the latter increasing to 14.3% among patients with ATPO titers > or = 18 IU/mL. IFN-alpha treatment significantly increased overall thyroid dysfunction (9.7%; P = .001) and hypothyroidism (7.8%; P = .01), particularly among patients with high baseline ATPO (38.5%; P = .0002). Six months after stopping IFN-alpha treatment, the prevalence of thyroid dysfunction was 8.0%, still significantly higher than at baseline. By multivariate analysis, the only predictor positively associated with pre- or on-treatment hypothyroidism was the baseline titer of the ATPO antibodies (relative risk [RR], 3.0 and 3.8 per each log titer increase, respectively). In conclusion, patients with chronic viral hepatitis on IFN-alpha treatment exhibit an almost threefold increase of baseline thyroid dysfunction, persisting long after the end of therapy. High ATPO titers, clustering among females, particularly those with hepatitis C, represent the only predictor of pre- and on-treatment hypothyroidism by multivariate analysis. Patients with chronic viral hepatitis, especially females, should be tested for ATPO and thyroid function and monitored during and posttreatment for free thyroxin (FT4) and thyroid-stimulating hormone (TSH) levels.

Thyroid abnormalities in chronic viral hepatitis and their relationship to interferon alfa therapy

The prevalence of antithyroid peroxidase antibodies (ATPO) and/or of thyroid dysfunction was studied in 422 patients with chronic viral hepatitis C, B, and D. Baseline results were compared with those during and 6 months after interferon alfa (IFN-alpha) therapy. The overall prevalence of ATPO among untreated patients was 14.1%, with no significant differences between chronic hepatitis C, B, or D, as well as between males and females. However, high ATPO titers (> or = 18 IU/mL) clustered significantly among females (8.7% vs. 3.4%; P = .022), especially those with chronic hepatitis C (11.2% vs. 3.6%; P = .036). Before treatment, 3.7% of the patients had thyroid dysfunction, mostly hypothyroidism (3.5%), the latter increasing to 14.3% among patients with ATPO titers > or = 18 IU/mL. IFN-alpha treatment significantly increased overall thyroid dysfunction (9.7%; P = .001) and hypothyroidism (7.8%; P = .01), particularly among patients with high baseline ATPO (38.5%; P = .0002). Six months after stopping IFN-alpha treatment, the prevalence of thyroid dysfunction was 8.0%, still significantly higher than at baseline. By multivariate analysis, the only predictor positively associated with pre- or on-treatment hypothyroidism was the baseline titer of the ATPO antibodies (relative risk [RR], 3.0 and 3.8 per each log titer increase, respectively). In conclusion, patients with chronic viral hepatitis on IFN-alpha treatment exhibit an almost threefold increase of baseline thyroid dysfunction, persisting long after the end of therapy. High ATPO titers, clustering among females, particularly those with hepatitis C, represent the only predictor of pre- and on-treatment hypothyroidism by multivariate analysis. Patients with chronic viral hepatitis, especially females, should be tested for ATPO and thyroid function and monitored during and posttreatment for free thyroxin (FT4) and thyroid- stimulating hormone (TSH) levels. (Hepatology 1997 Jul;26(1):206-10)