[Lymphocytoma cutis benigna. Case report of a 9 year old boy]. / Lymphocytoma cutis benigna. Falldarstellung eines 9-jährigen Jungen.

Infectious conditions of the infantile genitals are a diagnostic challenge. One of the rare differential diagnoses is lymphocytoma cutis benigna. We report a case of borrelial lymphocytoma of the glans penis in a 9 year old boy. Based on this case, the clinical, diagnostic and therapeutic aspects of this rare form of dermatoborreliosis are discussed.

Fibroadenoma of the breast in an 11-year-old girl.

Fibroadenoma is the main cause of unilateral breast mass in teenagers and adolescents. 4% of these are a special form described as giant or juvenile fibroadenoma. For primary diagnosis, ultrasound is the method of choice. The MRI allows exact evaluation of size and location. The fibroadenoma must be distinguished from the phylloid tumour, which can be malignant. The latter occurs in patients of all ages, but peaks between the ages 40 and 50 years. Only 2% of all primary malignant breast lesions are found in women aged under 25. Metastases of other primary tumours must be excluded, especially with a history of prior malignancies. When planning the surgical excision, the final cosmetic result is important. Although the main reason of an asymmetrical breast enlargement of young girls is a benign mass, an early surgical excision is efficient with regard to the best possible cosmetic outcome.

Concomitant administration of varicella vaccine with combined measles, mumps, and rubella vaccine in healthy children aged 12 to 24 months of age.

The reactogenicity and immunogenicity of three combined measles, mumps and rubella (MMR) vaccines and one administered with a varicella vaccine was studied in infants. The vaccines were Priorix (designated MeMuRu, Group 1), M-M-R II (Group 2), Triviraten (Group 3) and Priorix + a varicella vaccine, Varilrix (Group 4). Fever was greater in Group 2 (61.3%) compared to Group 1 (48.5%; p = 0.033) or Group 3 (37.1%; p = 0.009). Rash with fever was reported in Group 2 (4.8%) and Group 4 (3.3%), but not for Group 1. Anti-measles, -mumps and -rubella seroconversion was similar for Group 1 (96.1%, 96.1% and 100%, respectively), Group 4 (98% for all three), and Group 2 (91.5%, 93.6% and 97.9%) 60 days post-vaccination. GMTs for measles (3,053.7-3,412.2 mIU/ml), mumps (1,001.5-1,158.8 U/ml) and rubella (68.7-89.1 IU/ml) were similar for Groups 1, 2 and 4 at Day 60. Antibody persistence was noted 2 years post-vaccination. The MeMuRu + varicella combination showed no clinically relevant increase in reactogenicity and should facilitate introduction of a varicella vaccine into national immunization schedules.

Immunogenicity and reactogenicity of a single dose of a diphtheria--tetanus--acellular pertussis component vaccine (DTaP) compared to a diphtheria--tetanus toxoid (Td) and a diphtheria toxoid vaccine (d) in adults.

We compared immunogenicity and reactogenicity of a single dose of DTaP vaccine (containing tetanus and diphtheria toxoids and four acellular pertussis antigens) with conventional Td- or d-vaccines in 180 German adults. Antibody values against diphtheria and tetanus toxin and against the pertussis antigens fimbriae (FIM), filamentous hemagglutinin (FHA) and pertussis toxin (PT) were measured in pre- and post-immunization sera. Reactogenicity was determined by a patient diary card. Pre-immunization antibody values against diphtheria toxin were low in all three vaccine groups. After immunization, > or = 80% of the vaccinees in all three groups were fully protected (> or = 0.1 IU/ml), but geometric mean values were significantly higher in DTaP recipients compared to Td or d recipients (1.65 vs. 0.44 and 0.48, respectively; both P < 0.05). Pre-immunization antibody values against tetanus toxin were high in all three groups, and after immunization 100% of the vaccinees were protected (> or = 0.1 IU/ml). Furthermore, substantial antibody responses against pertussis antigens were elicited in DTaP recipients with geometric mean rises of 22.5, 4.1 and 7.5 for antibodies against FHA, fimbriae and PT, respectively. All three vaccines were well tolerated. Frequency and severity of local reactions were similar between DTaP and Td recipients and even less common in d recipients. Since DTaP did provide a significant boost of anti-pertussis antibodies and a significantly higher anti-diphtheria response than conventional Td vaccine without an increase of side effects, it might be an appropriate candidate for use in adults.

Comparison of immunogenicity and reactogenicity of a measles, mumps and rubella (MMR) vaccine in German children vaccinated at 9-11, 12-14 or 15-17 months of age.

Children aged 9-11, 12-14 or 15-17 months, respectively were vaccinated with a measles, mumps and rubella (MMR) vaccine and serum antibody responses and reactogenicity were compared. The data of 118 children could be analysed (group 1=9-11 months, n=46; group 2=12-14 months, n=29, group 3, 15-17 months, n=43). The only significant difference observed was for seroconversion against measles virus between group 1 and group 3 (84.8% vs 100%, p=0.012). No serious adverse events were reported. Local side reactions were mild, infrequent and independent of age. Immunisation against MMR is safe and effective even when administered before the currently recommended age of 12 months.

Clinical validation of a polymerase chain reaction assay for the diagnosis of pertussis by comparison with serology, culture, and symptoms during a large pertussis vaccine efficacy trial.

OBJECTIVE: To assess the diagnostic sensitivity and specificity of a Bordetella pertussis polymerase chain reaction (PCR) assay using nasopharyngeal (NP) specimens from subjects with cough illnesses participating in a large pertussis vaccine efficacy trial. DESIGN: From 1991 to 1994, we conducted a large pertussis vaccine efficacy trial in Germany to determine the efficacy of the Lederle/Takeda acellular pertussis component diphtheria-tetanus toxoids in comparison with the Lederle whole-cell component diphtheria-tetanus toxoids vaccine. In the final year of the follow-up period of this trial, a second NP specimen for PCR, in addition to a culture specimen and blood for specific serology (enzyme-linked immunosorbent assay), was collected by use of a Dacron swab in subjects or family members with cough illnesses >/=7 days duration or in subjects with exposure to a cough illness in a household member to establish a diagnosis of B pertussis infection. Oligonucleotide primers (pTp1 and pTp2) that amplify a 191-bp-sized DNA fragment from the pertussis toxin operon, which is specific for B pertussis, were used. The PCR-amplified products were visualized by dot blot analysis followed by hybridization with a digoxigenin labeled probe and rated as 1+, 2+, or 3+ in comparison with positive controls representing approximately 1 to 10, 11 to 50, and >50 B pertussis organisms, respectively. In the present analysis, we compare PCR findings with those of serology, culture, positive household contact, and clinical characteristics of cough illnesses. RESULTS: Of 392 subjects with NP specimens obtained for PCR, 376 also had NP specimens collected for culture and 282 had serum specimens. PCR and culture were positive in 86 (22%) and 23 (6%) subjects, respectively. Of the positive PCR specimens, 40 were rated 3+, 32 were rated 2+, and 14 were rated 1+; 3+ positive specimens were more prevalent among DT recipients compared with pertussis vaccine recipients. Illnesses in subjects with 3+ positive PCR results were more typical of pertussis than were those in subjects with 2+ and 1+ positive results with a mean duration of cough of 48 days versus 43 and 42 days, respectively; presence of paroxysms, whoop or vomiting in 38% versus 17% and 10%, respectively; and a clinical diagnosis of definite or probable pertussis by the investigators of 26% versus 7% and 4%, respectively. Using serologic evidence of infection as the standard, sensitivity of PCR was 61%, and specificity was 88%. For 3+ positive PCR results, the respective values were 42% and 97%. CONCLUSION: Our findings demonstrate that PCR is more sensitive than conventional culture for the diagnosis of pertussis. They also demonstrate a high specificity of PCR when serology with or without other confirmative criteria (culture and household contact) is used as the reference. Analysis of semiquantitative PCR results revealed that subjects with a 3+ PCR more frequently experienced typical illness compared with patients with 1+ or 2+ PCR. Although specific serologic study remains a necessity in pertussis research its modification for diagnosis in the clinical setting results in low sensitivity and specificity. Therefore, because PCR is more sensitive than culture and is easy to perform, it is a useful addition in the clinical setting.

Evidence of efficacy of the Lederle/Takeda acellular pertussis component diphtheria and tetanus toxoids and pertussis vaccine but not the Lederle whole-cell component diphtheria and tetanus toxoids and pertussis vaccine against Bordetella parapertussis infection.

A subanalysis of a recent cohort efficacy trial of a pertussis vaccine was performed to determine its efficacy against cough illnesses due to Bordetella parapertussis infections. Infants received four doses of either the Lederle/Takeda acellular pertussis component diphtheria and tetanus toxoids and pertussis (DTaP) vaccine or the Lederle whole-cell component diphtheria and tetanus toxoids and pertussis (DTP) vaccine at 3, 4.5, 6, and 15-18 months of age; controls received three doses of diphtheria and tetanus toxoids (DT) vaccine only. All subjects were prospectively followed for cough illnesses of > or = 7 days' duration; cases of B. parapertussis infection were confirmed by positive culture, household contact, or serology. Seventy-six cough illnesses due to B. parapertussis were identified; 24 occurred in 929 DTaP recipients, 37 in 937 DTP recipients, and 15 in 321 DT recipients, resulting in an efficacy of 50% for DTaP vaccine (95% CI [confidence interval], 5% to 74%) and 21% for DTP vaccine (95% CI, -45% to 56%). The data in the present analysis suggest that the Lederle/Takeda DTaP vaccine but not the Lederle whole-cell component DTP vaccine has efficacy against B. parapertussis infection.

A search for serologic correlates of immunity to Bordetella pertussis cough illnesses.

In a pertussis vaccine efficacy trial in Germany we collected sera from vaccinees (DTaP or DTP) after the third and fourth doses of vaccine or at comparable time periods in DT vaccine recipients. In addition, sera were collected from a randomized sample of subjects in each vaccine group at approximately 3-month intervals from which antibody kinetic curves were constructed, which allowed us to estimate specific antibody values to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin and fimbriae-2 at the time of exposure in the household setting. The imputed geometric mean antibody values to PT, pertactin and fimbriae-2 at the time of household exposure to Bordetella pertussis infection were higher (p < 0.07 or lower) in non-cases compared with cases. A multivariate (classification tree) analysis found that only pertactin and PT were significant in protection. Subjects with an imputed pertactin value of < 7 EU ml-1 had a 67% (18/27) chance of infection regardless of the PT value. If the pertactin value was > or = 7 EU ml-1 and the PT value > or = 66 EU ml-1 all subjects were non-cases. If the pertactin value was > or = 7 and the PT value was < 66 EU ml-1 the predicted probability of being a case was 31% (15/49). Logistic regression analysis also found that high versus low pertactin values were associated with illness prevention following household exposure. In the presence of antibody to pertactin, PT and fimbriae-2, the additional presence of antibody to FHA did not contribute to protection. Our data support historical data indicating that agglutinating antibodies are associated with protection and also recent serologic correlates data and clinical efficacy data which indicate that multicomponent vaccines containing pertactin and fimbriae have better efficacy than PT or PT/FHA vaccines.

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.

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.

Severe adverse events in a comparative efficacy trial in Germany in infants receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. The Pertussis Vaccine Study Group.

Severe adverse events were evaluated in 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 (DTP) or DT vaccine. Vaccinees received four doses (at three, four-and-a half, six and 15-18 months of age) of either DTP or DTaP vaccine or three doses at three, four-and-a half and 15-18 months of age) of DT vaccine. The analysis included 4,273 DTaP recipients, 4,259 DTP recipients and 1,739 DT vaccinees. Convulsions within three days of vaccination occurred in 1/15,912 doses in DTaP recipients and 1/3,926 doses in DTP vaccinees (p = 0.22). Persistent inconsolable crying was more common in DTP vaccinees (1/113 doses) compared with DTaP (1/497 doses, p < 0.001) and DT (1/359 doses, p < 0.001) recipients. High fever (< or = 40.5 degrees C) was less frequent in DTaP vaccinees (1/16,239 doses) compared with DTP (1/5,359) and DT recipients (1/4,665). One hypotonic-hyporesponsive episode was observed.

Minor adverse events in a comparative efficacy trial in Germany in infants receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. The Pertussis Vaccine Study Group.

Minor adverse events were evaluated in 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 (DTP) or DT vaccine. Vaccinees received four doses (at three, four-and-a half, six and 15-18 months of age) of either DTP or DTaP vaccine or three doses (at three, four-and-a half and 15-18 months of age) of DT vaccine. The reactogenicity analysis included 4,273 DTaP, 4,259 DTP and 1739 DT vaccinees. Local reactions (erythema and induration) and systemic events (fever, fretfulness, drowsiness and anorexia) were more common after each dose of DTP vaccine than after the DTaP and DT vaccine doses. Erythema, induration and fever increased in frequency in DTaP and DT recipients with increasing series number. Erythema, induration and fever after the first two doses of vaccine were more frequent in DT recipients than DTaP vaccinees. Antipyretics were more commonly used in DTP recipients than in DTaP vaccinees.

Clinical findings in Bordetella pertussis infections: results of a prospective multicenter surveillance study.

OBJECTIVE: To study the clinical presentation of culture-confirmed pertussis in children and their contacts with cough illnesses in an outpatient setting. METHODOLOGY: In conjunction with a large pertussis vaccine efficacy trial in Germany, a central laboratory to isolate Bordetella species from nasopharyngeal specimens was established in Erlangen in October 1990. Pediatricians in private practices in southern Germany, the Saar region, and Berlin were encouraged to obtain nasopharyngeal specimens and clinical characteristics from patients with cough illnesses >/=7 days' duration. Bordetella species were isolated by use of calcium alginate swabs, Regan-Lowe agar, and modified Stainer-Scholte broth. Clinical characteristics were determined by initial and follow-up questionnaires. RESULTS: From October 1990 to September 1996, 20 972 specimens were submitted, and B pertussis was isolated in 2592 instances (12.4%). Of the culture-proven cases, 50.7% were female, and the age range was 6 days to 41 years, with a mean and median of 4.3 years and 4.1 years, respectively. The following characteristics were noted. Only 4% of the patients had received pertussis vaccine. Of unvaccinated patients, 90.2% had paroxysmal cough, 78.9% demonstrated whooping, and 53.3% presented with posttussive vomiting; 5.7% had fever >/=38 degrees C. The duration of cough was /=21 days of spasmodic cough.

Bordetella pertussis infections and sudden unexpected deaths in children.

UNLABELLED: From December 1990 to November 1993 nasopharyngeal specimens were obtained for culture from 50 children (mean 4.9 +/- 3.3 months of age) who had died suddenly. Bordetella pertussis was not isolated. Subsequently, nasopharyngeal specimens for polymerase chain reaction (PCR) analysis were obtained from another 51 victims of sudden death (mean 5.4 +/- 4.4 months of age); nine (18%) were B. pertussis positive. CONCLUSION: Our findings support previous epidemiological studies which noted an association between epidemic pertussis and sudden infant death syndrome. Further PCR studies with both internal and external controls should be performed.

Antimicrobial activity and biocompatibility of polyurethane and silicone catheters containing low concentrations of silver: a new perspective in prevention of polymer-associated foreign-body-infections.

In modern medicine, infection is one of the most serious complications of implanted plastic devices. The host is not able to overcome this special type of opportunistic infection despite having a normal immune response and a low virulence of most of the bacteria involved. Antimicrobial therapy alone generally cannot cure the infection and the removal of catheters often remains the only choice of therapy. Bacterial adhesion to the polymer surface of the catheter, be it luminal or external, is an important step in the pathogenesis of catheter-associated infections. In this report, we describe new approaches to the prevention of infections by impregnation of polyurethane and silicone with silver by two different methods. The antimicrobial activity of these silver-impregnated catheters is more than 10 fold higher for coagulase-negative staphylococci (CNS) compared to catheters without silver. Similar results are obtained with other microbial organisms like Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. The new polymers show no cytotoxic or thrombogenic side effects in vitro.