Relative EBV antibody concentrations and cost of standard IVIG and CMV-IVIG for PTLD prophylaxis in solid organ transplant patients.

Some centers prefer CMV-IVIG over IVIG for the prophylaxis of EBV-related PTLD in solid organ transplant patients. Our objective was to compare the relative dose-related EBV ELISA antibody concentrations and cost of standard IVIG and CMV-IVIG. The concentration of EBV IgG to VCA was analyzed via ELISA in four lots of IVIG and four lots of CMV-IVIG. Relative EBV ELISA antibody concentrations and cost were compared assuming an IVIG dose of 0.5 gm/kg and CMV-IVIG dose of 0.15 gm/kg in a 50-kg patient. The price of IVIG was $70/gm and CMV-IVIG $430/gm. IVIG contains the same EBV antibody concentrations (20 790 ELISA antibody units/mL) than CMV-IVIG (17 430 ELISA antibody units/mL, p > 0.2) in the four lots of each product sampled. When factoring in the dosing scheme for a 50-kg patient, IVIG contains two times more EBV antibody than CMV-IVIG. Yet, CMV-IVIG is 1.8 times more expensive than IVIG ($3225 vs. $1750). In the four lots of each product sampled, IVIG contains more EBV antibodies and costs less than CMV-IVIG when factoring in the dosing scheme. Studies are needed to determine whether there is clinical efficacy of immunoglobulin products for EBV-related PTLD prophylaxis.

The respiratory pathology in infants with sudden unexpected deaths in whom respiratory specimens were initially PCR-positive or PCR-negative for Bordetella pertussis.

BACKGROUND: In a previous controlled study, we investigated the relationship between Bordetella pertussis infections and sudden unexpected deaths among German infants (sudden infant death syndrome, SIDS). In this present study, we investigated further the respiratory pathology in a subset of infants in the original study. METHODS: Originally, there were 234 infants with SIDS and, of these, 12 had either a nasopharyngeal swab (NPS) or a tracheal swab specimen (TS) that was positive for B. pertussis by polymerase chain reaction (PCR). Here, tissue specimens from eight infants who were originally PCR-positive were compared with tissue specimens from seven infants in whom the original PCR studies were negative. RESULTS: The histopathologic diagnoses were as follows: 14 of 15 had pulmonary edema and the remaining case had early diffuse alveolar damage. Although 14 of 15 cases had some histologic or clinical evidence suggesting respiratory tract infection, the features were more consistent with a viral etiology, and in none were the findings typical of respiratory disease attributable to B. pertussis. CONCLUSIONS: The findings in this present investigation do not support a direct role of B. pertussis at the site of infection (ciliated epithelium) in the causation of SIDS. The clinical aspects of this study were carried out in the 1990s when pertussis was widespread in Germany. Therefore, the original finding of some PCR-positive cases is not surprising. The possibility that B. pertussis infection could still be a factor in some SIDS cases, e.g., by a systemic release of toxins, cannot be definitely ruled out.

A clinical, epidemiologic, serologic, and virologic study of influenza C virus infection.

During a study of influenza-like illness in employees in the Pediatric Clinic at UCLA Hospital and Clinics in late November 1978, an influenza C viral strain was recovered from one employee, one person had more than a fourfold hemagglutination inhibition antibody titer rise to influenza C, and one person had specific influenza C IgM antibody. A survey of 334 children and young adults noted a seropositivity rate to influenza C of 64% for children up to 5 years old; 96% for 6- to 10-year-olds; 100% for 11- to 15-year-olds; and 98% for those over 16 years old. The 64% seropositivity of those children 5 years old and younger indicates that infection with influenza C early in life is common. The increasing seropositivity rates with age suggest that circulation and reinfection with influenza C commonly occurs.

Typical, modified, and atypical measles.

A small outbreak of measles that occurred in August and September of 1975 was studied. One adolescent boy who had received killed measles vaccine 12 years previously had atypical measles, a 31-year-old woman had typical primary measles, and two other boys with measles were live vaccine failures. Of these latter two cases, clinical and serologic findings suggest that one boy had primary vaccine failure and the other may have had a secondary immunologic response. The findings of this study, as well as the results of other recent investigations, suggest that measles will be of increasing concern for the internist.

The relationship between T-cell levels and CMV infection in asymptomatic HIV-1 antibody-positive homosexual men.

To investigate the relationship between cytomegalovirus (CMV) infection and progression of HIV-1 disease, a group of 234 asymptomatic, HIV-1 antibody-positive homosexual men were examined for CMV isolation and levels of CMV IgM antibodies, CMV IgG antibodies, and CD4+ and CD8+ T-lymphocytes. CMV IgG antibodies were present in 100% and CMV IgM antibodies in 22% of the men. CMV was isolated from the semen of 45% of the men. No relationship was observed between CMV IgM antibodies and CMV in semen or CD4+ levels. CD4+ cell levels were significantly lower in those from whose semen CMV was isolated. In addition, an inverse relationship was observed between the concentration of CMV in semen and CD4+ levels. We postulate that the seminal tract may be a reservoir for systemic CMV infection in HIV-infected homosexual men. Reinfection from this or other sources may result in recurrent stimulation of HIV-1 replication and lead to a further decline in CD4+ cells. Clarification of whether persistent CMV infection is secondary to HIV-1-induced immunodeficiency or, conversely, promotes a more rapid decline in immunocompetency will require follow-up studies.

DTP-associated reactions: an analysis by injection site, manufacturer, prior reactions, and dose.

Local and less serious systemic reactions are frequent following immunization with diphtheria-tetanus-pertussis (DTP) vaccine. The effects of injection site, manufacturer, previous reactions, and dosage reduction upon subsequent reactions to DTP immunization were investigated. Local reactions, notably pain and swelling, were less common when the immunization was given in the buttocks than in the thigh. No injection site was consistently associated with lower systemic reaction rates. There was no significant difference in the rate of more serious reactions by vaccine manufacturer. Differences in rates of less serious reactions by manufacturer were observed but seemed to be related to vaccine lot differences rather than the specific vaccines. In a subset of 772 children, in whom data regarding sequential reactions were available, it was noted that all three reactions investigated--local redness, temperature greater than or equal to 39 degrees C, and persistent crying longer than one-half hour--were two to three times more frequent on a subsequent immunization when present on a prior vaccination than if not present on a prior vaccination than if not present previously. One hundred children received a half dose of DTP vaccine because of a less serious reaction associated with prior immunization. In all instances, they had significantly less serious local reactions as well as notable differences in temperature, drowsiness, and persistent crying.

The effect of investigator compliance (observer bias) on calculated efficacy in a pertussis vaccine trial.

BACKGROUND: In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. DESIGN: In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of >/=7 days duration was noted, the study child was to be evaluated. If the cough illness persisted for >/=14 days, the child was to be referred to a central investigator. For this report we analyzed study physician evaluation rates and rates of referral to the central investigators. Physician practices were separated into three compliance categories: high, intermediate, and low. We analyzed vaccine efficacy of an acellular pertussis component DTP vaccine (DTaP) and a whole cell pertussis component DTP vaccine (DTP) by compliance category. Bordetella pertussis infection was documented by culture of the organism in the study child or in a household contact or by a significant antibody response to pertussis toxin determined by enzyme-linked immunosorbent assay. RESULTS: Using a clinical case definition that included both mild and typical pertussis (cough illness >/=7 days duration) efficacy of DTaP vaccine was 40% (95% confidence interval [CI] = -3-65) in the high compliance category and 78% (95% CI = 65-86) and 75% (95% CI = 53-87) in the intermediate and low compliance groups, respectively. Similar, but less marked, differences in efficacy were noted with DTP vaccine recipients. Using a clinical case definition that required >/=21 days of cough with paroxysms, whoop, or vomiting (typical pertussis) the efficacy of DTaP vaccine was 69% (95% CI = 41-83) in the high compliance category and 86% (95% CI = 76-92) and 84% (95% CI = 64-93) in the intermediate and low compliance groups, respectively. In contrast, the efficacy of DTP vaccine did not vary by compliance category using this case definition. The attack rate in children vaccinated with diphtheria and tetanus toxoids vaccine (DT) was twofold less in low compliance physician practices when compared with the rates in high and intermediate groups. The DT/DTaP and DT/DTP fold-change differences were less in the high compliance group compared with the intermediate and low compliance groups. CONCLUSIONS: Our data suggest that observer compliance (observer bias), can significantly inflate calculated vaccine efficacy. It is likely that all recently completed efficacy trials have been effected by this type of observer bias and all vaccines have considerably less efficacy against mild disease than published data suggest.

Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying.

OBJECTIVE: The pathophysiology of severe reactions to diphtheria-tetanus-pertussis (DTP)vaccine is not well understood. Active pertussis toxin in DTP vaccine has been proposed to cause severe DTP vaccine reactions. Large doses of pertussis toxin cause hyperinsulinemia and hypoglycemia as well as leukocytosis with a predominant lymphocytosis in animal models. To learn more about the causes of and risk factors for severe DTP vaccine reactions, children experiencing severe DTP vaccine reactions were studied. DESIGN: Prospective, referral-based surveillance. SETTING: Los Angeles, CA. SUBJECTS: Children experiencing severe reactions within 48 hours of DTP immunization and evaluated within 24 hours of the reaction. Severe reactions included encephalopathy, persistent crying > or = 3 hours, hypotonic-hyporesponsive episodes (collapse episodes), fever > or = 40.5 degrees C, or seizures. Some comparisons were made between children with DTP vaccine-associated seizures and a comparison group of children experiencing febrile seizures unrelated to immunization. OUTCOME MEASURES: A history and physical examination were performed. Follow-up examinations were performed 1 month later. Blood was collected for complete blood cell count with leukocyte differential count, serum chemistry measurements, and insulin and glucose values. Serum was assayed for active pertussis toxin, both in free and immune-complex masked states. RESULTS: Sixty children experienced severe reactions within 48 hours of DTP immunization: 32 children had seizures only, 14 subjects had hypotonic-hyporesponsive episodes, 2 subjects had fever > or = 40.5 degrees C only, 4 subjects had persistent crying > or = 3 hours, 6 children had seizures and fever > or = 40.5 degrees C, and 2 children had persistent crying and seizures. The children with seizures had a high rate of personal and family histories of seizures, and 90% had documented fevers (> or = 38 degrees C). Persistent crying was associated with painful local reactions. Effects that may have been due to vaccine pertussis toxin were not found. Lymphocytosis did not occur, nor did hypoglycemia. Some relatively elevated insulin values were noted; however, this finding was also noted in the comparison group of children experiencing febrile seizures unrelated to immunization. No biologically active pertussis toxin was found in the acute sera of children experiencing severe DTP vaccine reactions. CONCLUSIONS: Seizures associated with DTP vaccine have similar clinical characteristics as febrile seizures, and persistent crying is initiated by painful local reactions. Vaccine endotoxin is a cause of febrile DTP vaccine reactions. We found no evidence that DTP vaccine pertussis toxin plays a role in severe DTP vaccine reactions.

Clinical reactions and serologic responses after vaccination with whole-virus or split-virus influenza vaccines in children aged 6 to 36 months.

The reactogenicity and immunogenicity of whole-virus and split-product influenza vaccines were studied in 77 children between the ages of 6 and 36 months. Subjects initially received monovalent vaccine containing either A/USSR/77 (H1N1) antigen in 1978 or A/Brazil/78 (H1N1) antigen in 1979. One month later a trivalent preparation was given which contained the respective H1N1 antigen plus A/Texas/77 (H3N2) and B/Hong Kong/72 antigens. Temperatures of greater than or equal to 37.8 C (greater than or equal to 100 F) were observed more commonly after initial vaccination with whole-virus vaccine (35%) than after split-product vaccine (14%). No child had a temperature of greater than or equal to 39.4 C (103 F) or a febrile convulsion. The trivalent vaccines were more reactogenic than the monovalent vaccines although none of the reaction indices exceeded 0.9. The whole-virus vaccine appeared to be more immunogenic, especially in those children who were initially seronegative (preimmunization hemagglutination-inhibiting antibody titer (less than 5). Only 50% of children vaccinated with split-product vaccines with initial hemagglutination-inhibiting titers of less than 5 achieved titers of greater than or equal to 20 to the H1N1 antigen after two doses of vaccine compared with 97% in similar whole-virus vaccine recipients. The degree of antibody response to the A/Texas/77 component of the vaccines was greater than the response to the A/Brazil/78 or A/USSR/77 antigens.

Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children.

In 784 DT and 15,752 DTP immunizations given to children 0 to 6 years of age who were prospectively studied for reactions occurring within 48 hours following immunization, minor reactions were significantly more frequent following DTP vaccine. The ratio of reaction rates associated with DTP and DT immunizations (DTP/DT) for selected local and systemic reactions was as follows: local redness, 37.4%/7.6%; local swelling, 40.7%/7.6%; pain, 50.9%/9.9%; fever, 31.5%/14.9%; drowsiness, 31.5%/14.9%; fretfulness, 53.4%/22.6%; vomiting, 6.2%/2.6%; anorexia, 20.9%/7.0% and persistent crying, 3.1%/0.7%. Following DTP immunization nine children developed convulsions and nine developed hypotonic hyporesponsive episodes. No sequelae were detected following these reactions.

Infants and children with convulsions and hypotonic-hyporesponsive episodes following diphtheria-tetanus-pertussis immunization: follow-up evaluation.

In a prior prospective study, we evaluated the nature and rates of adverse reactions occurring within 48 hours following 15,752 diphtheria-tetanus-pertussis (DTP) immunizations. Nine children had convulsions, and nine had hypotonic-hyporesponsive episodes. After an interval of 6 to 7 years, we were successful in contacting the families of 16 of these children to determine whether any had evidence of neurologic impairment too subtle to have been detected at the time of initial evaluation. All 16 were considered normal by their parents and were doing well in school. A complete neurologic and psychometric evaluation was performed on 13 of these children. No child had significant neurologic deficit, although four had minor neurologic abnormalities. Psychometric testing revealed normal performance IQ scores (104.3 +/- 15.8) but low verbal IQ scores (91.8 +/- 18.4); however, these lower verbal IQ scores can be explained by the proportion of Hispanic and bilingual children in this sample. Therefore, there is no evidence that any of these 16 children have any serious neurologic damage as a result of a convulsion or a hypotonic-hyporesponsive episode temporally associated with a prior diphtheria-tetanus-pertussis immunization.

Extraintestinal amebiasis in infancy: report of three patients and epidemiologic investigations of their families.

Three infants (aged 6 weeks, 7 weeks, and 10 months) had severe Entamoeba histolytica infections characterized by colitis, hepatic abscesses, and peritonitis. The two younger children died after fulminant illnesses while the third recovered. Diagnosis was delayed in all three children by a low index of suspicion and negative stool examinations for parasites. Epidemiologic investigations of the infants' families revealed a high prevalence of amebic infections and elevated antibody titers to E histolytica; however, most family members were asymptomatic. The original source of the infections could not be identified but person-to-person spread within the families was implicated.

Comparative Efficacy of the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine and Lederle whole-cell component DTP vaccine in German children after household exposure. Pertussis Vaccine Study Group.

BACKGROUND: A household contact substudy was performed as part of a prospective, cohort pertussis vaccine efficacy trial in Germany. DESIGN: Infants received four doses of either the Lederle/Takeda acellular pertussis component diphtheria-tetanus toxoids (DTP) vaccine (DTaP) or Lederle whole-cell component DTP vaccine at 3, 4.5, 6, and 15 to 18 months of age (Wyeth-Lederle Vaccines and Pediatrics, Pearl River, NY). An open control group received three doses of diphtheria and tetanus toxoids vaccine (DT) at 3, 4.5, and 15 to 18 months of age. Vaccine efficacy rates were calculated using a number of principal and ancillary case definitions for primary, secondary, and noncases by analyzing secondary attack rates in study infants after exposure to pertussis in the household using 7- to 28- and 7- to 42-day postexposure observation periods and the inclusion and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period. RESULTS: During a 3.5-year study period, 10271 infants (DTP or DTaP, n = 8532; DT, n = 1739) were enrolled and actively followed along with all household members for cough illnesses. Depending on the case definition, 160 to 519 household exposures to pertussis were identified. In general, secondary attack rates in DT recipients were low and this was primarily because of the frequent use of antimicrobial prophylaxis. Using the principal case definitions and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period and the 7- to 42-day observation period, the efficacy of DTP against cough illness of greater than or equal to 7 days duration caused by Bordetella pertussis was 84% (95% confidence interval [CI] = 65-93) and that of DTaP was 58% (95% CI = 30-75). Using similar criteria, the efficacy against typical pertussis (greater than or equal to 21 days of cough with either paroxysms, whoop, or posttussive vomiting) was 94% (95% CI = 77-99) and 86% (95% CI = 62-95) for DTP and DTaP, respectively. The efficacy against any cough illness (with or without) laboratory confirmation was 54% (95% CI = 32-69) and 38% (95% CI = 13-56) for DTP and DTaP, respectively. CONCLUSION: This household contact substudy within our cohort study, with active investigator-generated surveillance, was a severe test of vaccine efficacy. Both vaccines (DTP and DTaP) are better at preventing typical pertussis than mild illness. When case definitions similar to those in other recent trials are used, the Lederle/Takeda vaccine has an efficacy similar to other multicomponent DTaP vaccines.

A comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP vaccine, or DT vaccine.

BACKGROUND: The goal of the trial was to determine the efficacy of a multicomponent acellular pertussis vaccine against Bordetella illnesses in comparison with a whole-cell product and DT. DESIGN: In a randomized, double-blind fashion, 2- to 4-month-old infants received 4 doses of either DTP or DTaP vaccine at 3, 4.5, 6, and 15 to 18 months of age. The controls received 3 doses (3, 4.5, 15 to 18 months of age) of DT vaccine. The DTP vaccine was Lederle adsorbed vaccine (licensed in the United States) and DTaP was Lederle/Takeda adsorbed vaccine. Follow-up for vaccine efficacy started 2 weeks after the third dose (DTP/DTaP) and at the same age (6.5 months) in DT recipients. Reactogenicity of all doses of all three vaccines was documented by standardized parent diary cards. In addition, all subjects were monitored for respiratory illnesses and serious adverse events by biweekly phone calls. RESULTS: From May 1991 to January 1993, a total of 10 271 infants were enrolled: 8532 received either DTP or DTaP and 1739 received DT. Specific efficacy against B pertussis infections with cough >/=7 days duration was 83% (95% confidence interval [CI]: 76-88) and 72% (95% CI: 62-79) for DTP and DTaP, respectively; results for DTP and DTaP based on >/=21 days of cough with either paroxysms, whoop or posttussive vomiting (PWV) were 93% (95% CI: 89-96) and 83% (95% CI: 76-88), respectively. For DTaP vaccine, efficacy was higher after the fourth dose as compared with its efficacy after the third dose (78% vs 62% for cough >/=7 days and 85% vs 76% for cough >/=21 days with PWV). For DTP vaccine, efficacy was less varied after the third and fourth dose (78% vs 85% for cough >/=7 days and 93% vs 93% for cough >/=21 days with PWV). In contrast with DTP, the DTaP vaccine had some efficacy against B parapertussis infection (point estimate for cough >/=7 days: 31% [95% CI: -10-56]). All vaccines were generally well-tolerated. However, side reactions were significantly less after DTaP compared with DTP. CONCLUSIONS: Like other multicomponent acellular pertussis vaccines, the Lederle/Takeda DTaP vaccine demonstrated good efficacy against mild and typical pertussis due to B pertussis infections. Interestingly, it also may have some efficacy against B parapertussis. Based on the results of this trial, the vaccine was licensed in the United States in December 1996 for all 5 doses of the currently recommended immunization schedule in this country.

Comparative efficacy of acellular pertussis vaccines: an analysis of recent trials.

Diphtheria-tetanus-acellular pertussis vaccines have been licensed in the United States since 1991. Compared with the whole cell pertussis component diphtheria-tetanus-pertussis vaccine, the diphtheria-tetanus-acellular pertussis vaccines were found in reactogenicity and immunogenicity studies to be immunogenic with respect to their specific antigen content and to be associated with less severe and less frequent adverse reactions. A case definition of pertussis was developed by the World Health Organization for use in vaccine efficacy trials, but this definition eliminates some laboratory-confirmed cases from efficacy calculations. Because these cases are more common in vaccinees than in controls, vaccine efficacy appears better than it truly is whereas less effective vaccines seem comparable with their more effective counterparts. In addition observer bias may contribute to the appearance of enhanced efficacy of the less effective vaccines, which tend to prevent typical but not mild disease. When analyzing efficacy based on prevention of laboratory-confirmed pertussis with cough > or = 7 days, single component pertussis toxin (PT) toxoid vaccines were found to be less effective than two-component PT toxoid/filamentous hemagglutinin vaccines, and three- or four-component vaccines containing pertactin in addition to PT toxoid and filamentous hemagglutinin were more effective than either the single-component or two-component vaccines.

Erythema migrans after ceftriaxone treatment of aseptic meningitis caused by Borrelia burgdorferi.

Erythema migrans is the characteristic exanthem of Lyme disease. The rash initially occurs at the site of inoculation; subsequently satellite lesions can occur. We describe an adolescent girl in whom the rash appeared after the initiation of ceftriaxone therapy for aseptic meningitis. We suggest that the occurrence of rash in this patient was a result of liberated toxin from local bacterial lysis.

Clinical and laboratory diagnosis of pertussis in the regions of a large vaccine efficacy trial in Germany.

As a support service for a pertussis vaccine efficacy trial, a central diagnostic laboratory was established. Physicians in the geographic areas of the planned study were encouraged to send nasopharyngeal specimens from children and household contacts with cough illnesses whether or not the illnesses were typical of pertussis. From April, 1991, to February, 1992, 3629 specimens were received and in 601 instances (16.6%) Bordetella pertussis was isolated. Only 3.3% of patients with positive cultures had received pertussis vaccine whereas 16.1% of culture-negative patients had received vaccine (P < 0.0001). Fever was more common (12.2%) in patients with negative cultures compared with those with positive cultures (5.4%) (P < 0.0001). B. pertussis isolation rates fell markedly after 21 days of cough. Significantly more patients with negative cultures compared with those with positive cultures had been treated with erythromycin (8.5 vs. 2.9%; P < 0.0001). Patients with cough for greater than 4 weeks and specimen collection within 2 weeks of cough onset had a B. pertussis isolation rate of 59%. Similarly if whoop occurred under the same circumstances the isolation rate was 80%. In this study 25.5% of patients with culture confirmed pertussis had illnesses with cough of less than 21 days duration. This finding suggests to us that a pertussis case definition in efficacy trials that requires cough of 21 days is excessively restrictive.

Use of aminoglycosides during cyclosporine A immunosuppression after liver transplantation in children.

To determine the frequency of renal dysfunction associated with the use of aminoglycosides with cyclosporine A (CyA) in children, the records of 26 consecutive children receiving CyA after liver transplantation were reviewed. Fourteen patients with normal baseline serum creatinine concentrations received an aminoglycoside postoperatively. These children received CyA and an aminoglycoside for 249 days (average, 17.8 days/patient). Forty of the 249 days included treatment with vancomycin or amphotericin B. Twelve children (86%) showed no evidence of renal dysfunction after aminoglycoside therapy. Two children developed renal dysfunction and eventually succumbed. In neither case could aminoglycoside nephrotoxicity be identified as the main cause of renal dysfunction. Multiple other factors, including ischemia and high CyA concentrations, probably contributed to renal deterioration. We conclude that aminoglycosides can be used safely in children receiving CyA following liver transplantation, provided serum CyA concentrations are followed closely and other risk factors for renal dysfunction are minimized.

Analyses of adverse reactions to diphtheria and tetanus toxoids and pertussis vaccine by vaccine lot, endotoxin content, pertussis vaccine potency and percentage of mouse weight gain.

We investigated the rates of local and systemic reactions following 9920 diphtheria-tetanus toxoids-pertussis immunizations from 25 lots of commercially available, United States-licensed diphtheria-tetanus toxoids-pertussis adsorbed vaccines from four manufacturers as a function of vaccine lot, endotoxin content, pertussis vaccine potency and percent of mouse weight gain. There were significant differences between the rates of reactions by lot for all local and systemic reactions except convulsions and hypotonic hyporesponsive episodes. For these latter reactions there were insufficient cases for analyses. P was less than 0.0001 for local reactions, fever, drowsiness, fretfulness, anorexia and screaming and 0.017 for vomiting. No single lot was associated with the highest or lowest rate of reactions for more than 3 of the 11 reactions. There was a significant positive association of endotoxin unit (EU) content and the percent of vaccine recipients who developed fever (P = 0.004). Fever increased in frequency from 20.6% of children immunized with vaccine lots that contained 2500 EU to 55.1% of children immunized with vaccine lots containing 40,000 EU. There were significant positive associations of all local reactions and pertussis vaccine potency (P = 0.0004), and percent of mouse weight gain (P less than 0.0001). There was also a positive association of percent mouse weight gain and persistent screaming (P = 0.001). However, for the majority of reactions there was no clinically meaningful associations between reaction rates and the biological properties of the vaccine studied.

Polymerase chain reaction identification of Bordetella pertussis infections in vaccinees and family members in a pertussis vaccine efficacy trial in Germany.

The polymerase chain reaction (PCR) was recently added to conventional culture and serology for the diagnoses of Bordetella pertussis infection in a large vaccine efficacy trial in Germany. In vaccinees or family members who had illnesses with cough, two nasopharyngeal swabs (calcium alginate for culture and Dacron for PCR) were taken and initial and follow-up clinical data were obtained. PCR was done using oligonucleotide primers PTp1 and PTp2 which amplify a 191-base pair DNA fragment of pertussis toxin operon. From December, 1993, to May, 1994, 555 pairs of swabs were processed; 28 grew B. pertussis and 9 grew B. parapertussis. Twenty-six of the 28 subjects with B. pertussis-positive cultures also had positive PCR results as did one of the 9 B. parapertussis cases and 82 additional samples were positive by PCR. PCR increased the identification of subjects with B. pertussis infections by almost 4-fold. Clinical characteristics were analyzed by laboratory category (Group 1, 28 culture-positive; Group 2, 82 culture-negative, PCR-positive; and Group 3, 436 culture- and PCR-negative). Group 1 subjects were more likely to have a diagnosis of definite or probable pertussis and to have paroxysmal cough, posttussive vomiting, whooping and a cough duration of > or = 4 weeks than Group 2 or 3 subjects. In contrast Group 2 subjects were more likely than Group 1 subjects to have had previous pertussis immunization or prior antibiotics. PCR identified many mild illnesses caused by B. pertussis that were not identified by culture.