Gene Ontology annotations and resources.

The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new 'phylogenetic annotation' process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources.

[Clinical evaluation of the new coat colour macchiato in a male Franches-Montagnes horse]. / Klinische und genetische Befunde bei einem männlichen Freiberger mit der neuen Fellfarbe Macchiato.

In April 2008 a Franches-Montagnes colt was born with an unusual coat colour phenotype which had never been observed in that population before. The foal showed extended white markings on body and legs, a white head and blue eyes. As both parents have an unremarkable bay coat colour phenotype, a de novo mutation was expected in the offspring and a candidate gene approach revealed a spontaneous mutation in the microphthalmia associated transcription factor gene (MITF). A detailed clinical examination in 2010 indicated an impaired hearing capacity. As in the American Paint Horse large white facial markings in combination with blue eyes are associated with deafness, the hearing capacity of the stallion was closer examined performing brainstem auditory-evoked responses (BAER). The BAER confirmed bilateral deafness in the Franches-Montagnes colt. It is assumed that the deafness is caused by a melanocyte deficiency caused by the MITF gene mutation. Unfortunately, due to castration of the horse, the causal association between the mutation in the MITF gene and clinical findings cannot be confirmed by experimental matings.

[The effect of oral calcium lactate in postpartum cows]. / Untersuchungen zur Wirkung von Kalziumlaktat bei Kühen post partum.

The oral administration of calcium lactate for prophylaxis of bovine parturient paresis has been promoted for a number of years. The goal of the present study was to investigate the effect of this treatment on the serum concentrations of calcium, inorganic phosphorus and magnesium in parturient cows. Five fresh calved cows were given a drench containing calcium lactate and 5 control cows received the same drench but without calcium lactate. There were no significant differences in the serum concentrations of total and ionised calcium and magnesium between treated and control cows within 24 hours of treatment. Because the calcium lactate drench did not significantly affect calcium concentrations in the blood of fresh cows, it appears highly questionable whether the administration of calcium lactate decreases the risk of bovine parturient paresis. Based on our results, the oral administration of calcium lactate can not be recommended for prophylaxis of bovine parturient paresis.

Treatment of cows with milk fever using intravenous and oral calcium and phosphorus.

Fifteen cows with milk fever were treated with 500ml of 40 % calcium borogluconate (group A) administered intravenously. Fifteen other cows with milk fever received the same treatment, supplemented with 500ml of 10 % sodium phosphate administered intravenously, and 80g calcium as calcium lactate and 70g inorganic phosphorus as sodium phosphate administered orally in drinking water. The cows were monitored and blood samples collected for 3 days to measure the concentrations of total and ionized calcium, inorganic phosphorus and magnesium and the activity of creatine kinase. The two groups did not differ significantly with respect to the course of the disease. In each group 14 cows were cured. A rapid and significant increase in serum calcium concentration from the hypo- to the hypercalcaemic range occurred in both groups within 10min of the start of treatment, followed by a slow and steady decrease to the hypocalcaemic range. Calcium lactate did not prevent the calcium concentration from returning to the hypocalcaemic range, and the calcium profiles of the two groups did not differ significantly. As expected, treatment had little effect on the concentration of inorganic phosphorus in group A. In group B, treatment caused a rapid increase in the concentration of inorganic phosphorus to a maximum 20min after the start of treatment. This was followed by a slow decrease in the phosphorus concentration to the normophosphataemic range. Our findings confirmed that combined intravenous and oral administration of sodium phosphate in cows with periparturient paresis attributable to hypocalcaemia and hypophosphataemia results in a rapid and sustained increase in serum phosphorus, but not in serum calcium concentration. This modified therapy did not improve the success rate of milk fever treatment and further studies are needed to improve treatment of periparturient paresis.

Fenofibrate treatment for severe hypertriglyceridemia in dogs.

Lipid disorders are relatively common in dogs. Hyperlipidemia can be primary or secondary to other diseases. In humans, fenofibrate is used to control hypertriglyceridemia. In dogs, there are no studies evaluating fenofibrate in hypertriglyceridemia. The aim of the study was to evaluate the safety and efficacy of fenofibrate to control severe hypertriglyceridemia in dogs. A total of 124 dogs (n = 124) with severe hypertriglyceridemia (>300 mg/dL, 3.39 mmol/L) were randomly distributed in the fenofibrate group (n = 64) and the diet group (n = 60). Dogs of the fenofibrate group were treated with fenofibrate (10 mg/Kg) once daily. Dogs of the diet group were treated with low-fat diet (10%). Serum triglycerides (TGs), total cholesterol (TC), liver enzymes, and creatine kinase concentrations were evaluated, before and after 1 mo of medical or dietary treatment. Triglyceride concentrations were reduced with fenofibrate (P < 0.001), and 85.93% of the dogs normalized their levels. Triglyceride concentrations also decreased with low-fat diet (P < 0.001), but only 26.6% of the dogs normalized their levels. Triglyceride concentrations were reduced with fenofibrate (P < 0.01) and with low-fat diet (P < 0.01). Of the cases with hypercholesterolemia, 53.7% and 50% of the dogs normalized their TC concentrations, with fenofibrate and diet, respectively. No significant adverse effects were observed (3% showed diarrhea). Fenofibrate was safe and effective in reducing and normalizing TG concentrations in dogs with severe hypertriglyceridemia, regardless of the cause of hyperlipidemia. The low-fat diet was effective in reducing, but not normalizing, TG concentrations. Fenofibrate and low-fat diet were effective in reducing TC concentrations. This is the first study evaluating fibrates in dogs with severe hypertriglyceridemia and comparing results with a low-fat diet.

Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years.

BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).

Diurnal ACTH and plasma cortisol variations in healthy dogs and in those with pituitary-dependent Cushing's syndrome before and after treatment with retinoic acid.

Daytime variations in ACTH and plasma cortisol were studied in healthy dogs and in dogs with pituitary-dependent hypercortisolism (PDH), before and after treatment with retinoic acid. In control dogs ACTH showed a higher concentration at 8.00 AM and between 2.00 and 6.00 PM, with the lowest concentration registered at 10.00 AM (p<0.05 vs. 8.00 AM and 2.00 PM and p<0.01 vs. 4.00 PM). Cortisol did not show significant differences. In dogs with PDH, ACTH was lower at 8.00 AM (ACTH: p<0.01 vs. 2.00 and 4.00 PM; and p<0.05 vs. 6.00 PM). The lowest cortisol concentration was registered at 8.00 AM and 8.00 PM and the highest at 4.00 PM (p<0.05 vs. 8.00 AM and p<0.01 vs. 8.00 PM). After treatment, the lowest ACTH concentration was registered at 10.00 AM (p<0.01 vs. 2.00 and 4.00 PM). To conclude, the adrenal is desensitized in PDH possibly showing negative in diagnostic tests.

Cushing's disease in dogs: cabergoline treatment.

The treatment of pituitary-dependent hyperadrenocorticism (PDH) in dogs has for a long time been focused on inhibiting the adrenal gland using drugs such as o-p'-DDD, Ketoconazole and Trilostane, without attacking the primary cause: the corticotrophinoma. Corticotroph cells can express the D2 dopaminergic receptor; therefore cabergoline (Cbg) could be effective as a treatment. Follow-up over 4 years was carried out in 40 dogs with PDH that were treated with Cbg (0.07 mg/kg/week. Out of the 40 dogs, 17 responded to Cbg (42.5%). A year after the treatment, there was a significant decrease in ACTH (p<0.0001), alpha-MSH (p<0.01), urinary cortisol/creatinine ratio (p<0.001), and of the tumor size (p<0.0001) evaluated by nuclear magnetic resonance. Dogs responding to Cbg lived significantly longer (p<0.001) than those in the control group. To conclude, Cbg is useful in 42.5% of dogs with PDH, justifying its use as a treatment.

Post-surgical treatment of thyroid carcinoma in dogs with retinoic acid 9 cis improves patient outcome.

The objective of the present study was to compare the effects of isotretinoin 9-cis (RA9-cis) as a post-surgery treatment of thyroid carcinoma to a traditional treatment (doxorubicin) and no treatment. Owners who did not want their dogs to receive treatment were placed into the control group A (GA; n=10). The remaining dogs were randomly placed into either group B (GB; n=12) and received doxorubicin at a dose of 30 mg/m(2) every three weeks, for six complete cycles or group C (GC; n=15) and treated with RA9-cis at a dose of 2 mg/kg/day for 6 months. The time of the recurrence was significantly shorter in the GA and GB compared to GC (P=0.0007; P=0.0015 respectively), while we did not detect differences between GA and GB. The hazard ratio of recurrence between GA and GB compared to GC were 7.25 and 5.60 times shorter, respectively. We did not detect any differences between the other groups. The risk ratio of recurrence was 2.0 times higher in GA compared to GC and 2.1 times higher in GB compared to GC. The type of carcinoma had an effect on time of survival with follicular carcinomas having an increased mean survival time than follicular-compact carcinomas (P<0.0001) and follicular-compact carcinomas had a longer mean survival time than compact carcinomas. The interaction among treatment and type was significant, but survival time in follicular carcinomas did not differ between treatments. In follicular-compact carcinomas the survival time of GC was greater than GB (P<0.05), but we did not detect a difference between GA and GB. In conclusion, this study shows that the use of surgery in combination with RA9-cis treatment significantly increases survival rate and decreases the time to tumor recurrence when compared to doxorubicin treated or untreated dogs. The histological type of carcinoma interacted with treatment for time to recurrence and survival time, with more undifferentiated carcinomas having a worse prognosis than differentiated carcinomas.

Distribution of apolipoprotein E between free and A-II complexed forms in very-low- and high-density lipoproteins: functional implications.

The stability of apolipoprotein E/lipoprotein associations has been examined as a function of apolipoprotein E phenotype. Visualisation by immunoblotting showed plasma apolipoprotein E to be present in two forms; the free form and, as previously described, an E-A-II complex. In very low density lipoproteins isolated by gel filtration from subjects with E3/3 and E4/3 phenotypes, apolipoprotein E was present essentially in the free form (ratio free: complex of 12.2 and 37.5, respectively). Exploiting ultracentrifugation as the disruptive agent, very-low-density lipoproteins thus isolated were shown to have substantially lower ratios (5.6 and 5.4, respectively) reflecting preferential loss of free apolipoprotein E. In high-density lipoproteins isolated by gel filtration from E3/3 phenotypes, apolipoprotein E was largely present as an E-A-II complex (80.3%). In contrast, the majority of apolipoprotein E in high-density lipoproteins from E4/3 phenotypes was present in the free form (58.7%). In both phenotypes, the content of free apolipoprotein E was markedly reduced by ultracentrifugation. The results confirm the notion that the formation of the E-A-II complex is a major determinant of the stability of apolipoprotein E-high-density lipoprotein associations. Moreover, that the predominant, ancestral isoform, apolipoprotein E3, exists largely as an E-A-II complex in higher density lipoproteins has important functional implications for this plasma source of apolipoprotein E.

A novel high-density lipoprotein particle and associated protein in rat plasma.

This report describes the characterization of a novel rat apolipoprotein, which, as partial sequencing suggests, does not correspond to any described protein. The protein (termed PX) has an estimated molecular mass of 19.5 kDa and pI in the range 5.5-5.8. Monoclonal antibodies were obtained against protein PX and results on distribution among rat lipoproteins show it to be associated mainly with high-density lipoproteins (HDL), but also with VLDL. Immunoaffinity chromatography of total HDL shows protein PX to be included in a distinct lipoprotein particle, particularly enriched in free cholesterol, with which only traces of other apolipoproteins are associated. Immunologically crossreacting entities are found in the plasma of several species, including man. Retention of the epitope carried by the protein PX would suggest that it is of particular structural or functional importance. It remains to be established whether its function is associated with lipid metabolism.

The membrane-anchoring systems of vertebrate acetylcholinesterase and variant surface glycoproteins of African trypanosomes share a common antigenic determinant.

Amphiphilic detergent-soluble acetylcholinesterase (AChE) from Torpedo is converted to a hydrophilic form by digestion with phospholipase C from Trypanosoma brucei or from Bacillus cereus. This lipase digestion uncovers an immunological determinant which crossreacts with a complex carbohydrate structure present in the hydrophilic form of all variant surface glycoproteins (VSG) of T. brucei. This crossreacting determinant is also detected in human erythrocyte AChE after digestion with T. brucei lipase. From these results we conclude that the glycophospholipid anchors of protozoan VSG and of AChE of the two vertebrates share common structural features, suggesting that this novel type of membrane anchor has been conserved during evolution.

Actin stress fiber content of regenerated endothelial cells correlates with intramural retention of intermediate plus low density lipoproteins in rat aorta after balloon injury.

The rat aortic model of endothelial injury (balloon catheter induced) has been used to establish whether changes in protein intramural penetration in specific areas of the injured aorta were accompanied by phenotypic modifications of the regenerated endothelial cells covering these particular regions. Iodinated lipoproteins (IDL/LDL fraction) and albumin were used as tracers to localize protein permeability and retention in the aorta. Lipoproteins, but not albumin, were retained in the thickened areas covered with regenerated endothelium (i.e., 60 days after balloon induced injury). Neither lipoproteins nor albumin were retained in the other aortic areas studied, including the intimal thickening of de-endothelialized areas (15 days after injury). The relative volume of cytoplasmic stress fibers was significantly increased in regenerated endothelium covering thickened areas as compared with the other regions of the injured or normal aorta. The accumulation of lipids usually observed in atherosclerotic lesions, compatible with the trapping of lipoproteins by the matrix component of the intimal thickening, may be related to modulated features of endothelial cells regenerated over thickened areas of the aorta.

Immunogenicity of subcutaneous versus intramuscular Oka/Merck varicella vaccination in healthy children.

To compare the immunogenicity and safety of varicella vaccine by either subcutaneous or intramuscular injection, 166 healthy children aged 12 months to 10 years old who had no prior history of varicella were enrolled from two pediatric practices and randomly assigned to receive 0.5 mL of a single lot of varicella vaccine. Sera from the day of and 6 weeks postvaccination were tested for varicella antibody by gpELISA. Parents recorded clinical events occurring in the 6 weeks following vaccination. In the 132 evaluable children, the mean prevaccination titer was 0.3 gpELISA units for both groups. Sixty-three (97%) of the 65 receiving varicella vaccine by the subcutaneous route seroconverted compared with 67 (100%) of 67 immunized intramuscularly. Postvaccination geometric mean titer in the subcutaneous group was 6.9 +/- 7.0 gpELISA units and did not differ significantly from the geometric mean titer of 10.5 +/- 4.4 in the intramuscular group. Varicella vaccine was generally well tolerated by either route; 21% of both groups complained of reactions at the injection site and 7% had a varicella-like rash. Although varicella vaccine is recommended to be given subcutaneously, the results of this study indicate that inadvertent intramuscular administration of varicella vaccine is not reason for revaccination.

Acellular pertussis vaccination of 2-month-old infants in the United States.

This is the first study in children from the United States that evaluates the immunogenicity of and adverse reactions to the Connaught/Biken two-component acellular pertussis vaccine compared with whole-cell pertussis vaccine when given as a primary immunization series at 2, 4, and 6 months of age. Three hundred eighty infants were studied; 285 received acellular diphtheria-tetanus toxoids-pertussis (DTP (ADTP)) and 95 received whole-cell DTP (WDTP). Following the third dose, ADTP vaccination produced higher antibody responses than WDTP to lymphocytosis-promoting factor (enzyme-linked immunosorbent assay IgG geometric mean titer (GMT) = 131 vs 9 and Chinese hamster ovary cell assay GMT = 273 vs 16) and to filamentous hemagglutinin (IgG GMT = 73 vs 10) (all P less than .0001). Agglutinin responses were higher in WDTP compared with ADTP recipients (GMT = 50 vs 37; P = .02). Local reactions were fewer for all three doses following ADTP vaccination. Fever, irritability, drowsiness, anorexia, vomiting, and unusual crying all occurred less frequently in ADTP compared with WDTP recipients for one or more of the three doses. We conclude that this two-component ADTP vaccine when given as a primary series produces greater immunogenicity and fewer adverse effects than the currently licensed WDTP vaccine.

Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial.

A total of 536 infants and children with acute otitis media were randomly assigned to one of six consistent year-long regimens involving the treatment of nonsevere episodes with either amoxicillin or placebo, and severe episodes with either amoxicillin, amoxicillin and myringotomy, or, in children aged 2 years or older, placebo and myringotomy. Nonsevere episodes had more favorable outcomes in subjects assigned to treatment with amoxicillin than with placebo, as measured by the proportions that resulted in initial treatment failure (3.9% vs 7.7%, P = .009) and the proportions in which middle-ear effusion was present at 2 and 6 weeks after onset (46.9% vs 62.5%, P less than .001; and 45.9% vs 51.5%, P = .09, respectively). In subjects whose entry episode was non-severe, those assigned to amoxicillin treatment had less average time with effusion during the succeeding year than those assigned to placebo treatment (36.0% vs 44.4%, P = .004), but recurrence rates of acute otitis media in the two groups were similar. In the 2-year-and-older age group, severe episodes resulted in more initial treatment failures in subjects assigned to receive myringotomy alone than in subjects assigned to receive amoxicillin with, or without, myringotomy (23.5% vs 3.1% vs 4.1%, P = .006). In the study population as a whole, severe episodes in subjects assigned to receive amoxicillin alone, and amoxicillin with myringotomy, had comparable outcomes. It is concluded that children with acute otitis media should routinely be treated with amoxicillin (or an equivalent antimicrobial drug). The data provide no support for the routine use of myringotomy either alone or adjunctively.

Comparison of a three-component acellular pertussis vaccine with a whole-cell pertussis vaccine in 15- through 20-month-old infants.

OBJECTIVE: To compare the immunogenicity and reactogenicity of a diphtheria and tetanus toxoids and three-component acellular pertussis vaccine (DTaP) with a diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) when administered as a booster dose to infants 15 through 20 months of age. DESIGN: Randomized, double-blind, comparative study. SETTING: Three pediatric practices (two private; one hospital-based). PARTICIPANTS: One hundred and sixty-five healthy 15- through 20-month old infants. SELECTION PROCEDURES AND INTERVENTIONS: Infants were randomly assigned in a 2:1 ratio to receive vaccine from a single lot of DTaP or from commercially available DTwP. DTaP contained 25 micrograms of pertussis toxoid, 25 micrograms of filamentous hemagglutinin, 8 micrograms of pertactin (69-kilodalton outer membrane protein), 25 flocculating units of diphtheria toxoid, and 10 flocculating units of tetanus toxoid per 0.5-mL dose. DTwP contained one half the concentrations of diphtheria and tetanus toxoids compared with DTaP and a pertussis component with a potency of 4 U/0.5-mL dose. Serum samples were obtained on the day of immunization and 4 weeks later. Adverse reactions were recorded by parents for 7 days after immunization. An interval history was obtained 4 weeks after immunization. MEASUREMENTS AND RESULTS: IgG antibody to pertussis toxoid, filamentous hemagglutinin, pertactin, diphtheria toxoid, and tetanus toxoid was measured by an indirect enzyme-linked immunosorbent assay (ELISA) method. One month after immunization, the geometric mean antibody levels after DTaP compared with DTwP were: pertussis toxoid, 70.6 vs 28 ELISA U/mL (P = .003); filamentous hemagglutinin, 183.4 vs 43 ELISA U/mL (P < .001); pertactin, 216 vs 49.9 ELISA U/mL (P < .001); diphtheria, 14.1 vs 14.9 IU/mL (P = .74); and tetanus, 11.9 vs 14.8 IU/mL (P = .089). After immunization with DTaP, most local and systemic adverse experiences were significantly fewer compared with DTwP (P < .05). CONCLUSIONS: This three-component DTaP vaccine demonstrates significantly greater immune responses to pertussis toxoid, filamentous hemagglutinin, and pertactin, equivalent immune responses to diphtheria and tetanus toxoids, and significantly less reactogenicity compared with a licensed DTwP.

Safety and immunogenicity of a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b vaccine in young infants.

OBJECTIVE: To study the safety and immunogenicity of a combined diphtheria-tetanus-pertussis (DTP)-Haemophilus influenzae type b (HbOC) vaccine (TETRAMUNE) in infants as young as 2 months of age as compared to separate administration of DTP and HbOC. METHODS: Two-month-old infants were randomized to receive three doses 2 months apart of either DTP-HbOC as a single 0.5-mL injection or to receive 0.5 mL of DTP and HbOC concurrently in separate legs. Local and systemic adverse reactions were monitored within 72 hours of each immunization, and immunogenicity of each of the four vaccine components was measured. RESULTS: The incidence of both local and systemic adverse events following the tetravalent vaccine was similar to the incidence following separate vaccine administration. After three doses of vaccine, the response to each of the vaccine components was higher in the combined vaccine when compared to separate administration. In the case of the Haemophilus influenzae type b component, this enhancement was also seen after two doses. The response to the combined vaccine was consistent among the three lots tested as was the enhancement over separate administration. CONCLUSIONS: The DTP-HbOC vaccine was safe and immunogenic in young infants and was generally more immunogenic than separate vaccination with DTP and HbOC. The use of such a combined vaccine reduces the number of injections given to young infants by half and is an important step toward improving vaccine delivery.

Clinical survey of natural varicella compared with breakthrough varicella after immunization with live attenuated Oka/Merck varicella vaccine.

OBJECTIVE: To prospectively characterize varicella occurring in children previously immunized with a live attenuated varicella vaccine (breakthrough varicella) through daily observation by medical personnel and to compare it with natural varicella followed in the same manner. DESIGN: A blinded clinical survey. SETTING: Four pediatric practices (two private; two hospital-based). PARTICIPANTS: Healthy 12-month-old through 17-year-old children with chickenpox were studied; 92 had natural varicella and 58 had breakthrough varicella. SELECTION PROCEDURES AND INTERVENTIONS: Study personnel, unaware of vaccination status, documented the clinical characteristics of each patient in the office or at the patient's home each day from enrollment until the day after the total number of lesions increased less than 10%. A standard form documenting number and description of lesions, temperature, duration of illness, and associated clinical complaints was completed each day by the same study personnel. Acute and convalescent sera were obtained on breakthrough cases. MEASUREMENTS AND RESULTS: Antibody to varicella-zoster virus was measured by the glycoprotein-based enzyme-linked immunosorbent assay. Of those with sera available, 85% were serologically confirmed. Eighty-seven percent of enrollees had a known exposure to chickenpox, with at least two thirds of each group having a greater than 4-hour or a household exposure. The numbers of total and vesicular lesions were significantly higher in the natural varicella group, regardless of exposure status (P = .021 to < .001). The group with breakthrough varicella had a significantly lower incidence of fever (P < .001) and a significantly shorter duration of illness (P < .001). Other associated constitutional complaints and complications were not significantly different between groups. CONCLUSION: Varicella in vaccine recipients is clinically modified and significantly less severe than natural disease.

Safety and immunogenicity of acellular pertussis vaccine combined with diphtheria and tetanus toxoids in 17- to 24-month-old children.

A double-blind, randomized, controlled trial comparing 4 lots of acellular pertussis-diphtheria tetanus toxoids vaccine (APDT) to whole cell DTP vaccine in 397 children was conducted at 7 clinical centers. Children were immunized at 17 to 24 months of age and sera were obtained pre- and postimmunization. Sera were analyzed for antibody to pertussis antigens (pertussis toxin, filamentous hemagglutinin, with a molecular weight of 69,000 (69k) outer membrane protein and agglutinogens) and to diphtheria and tetanus toxoids. Information concerning local reactions and systemic events was collected daily for 10 days postimmunization. The acellular vaccine produced significantly fewer local reactions than whole cell DTP. Parents reported that drowsiness or fretfulness occurred significantly less often in APDT vaccine recipients compared with whole cell DTP recipients. Fever greater than or equal to 38.3 degrees C occurred in 8% of APDT vaccine recipients and in 15% of whole cell DTP vaccine recipients (P = 0.06). The only significant difference in immune response to pertussis antigens between the two vaccines was for filamentous hemagglutinin (P less than 0.01) for which significantly higher antibody concentrations were found in the APDT vaccine group. We conclude that this APDT vaccine is safe and immunogenic when administered as a booster dose to 18-month-old children.