Measles vaccine immunogenicity in 6- versus 15-month-old infants born to mothers in the measles vaccine era.

HYPOTHESIS: The low titer of measles antibody in infants of mothers with vaccine-induced immunity may allow immunization against measles before 15 months of age. METHODS: Six- and 15-month-old infants born to mothers < or = 30 years of age with no history of measles were recruited. Infants enrolled at 6 months of age were immunized with monovalent measles vaccine (Attenuvax), and maternal serum and infant pre- and postvaccination sera were obtained. Those enrolled for primary vaccination at 15 months of age received either Attenuvax (N = 12) or M-M-RII (N = 3). Six-month-old infants were revaccinated with M-M-RII at 15 months of age; pre- and postrevaccination sera were again obtained. Three antibody assays were used: a measles neutralizing assay (NT) and two enzyme immunoassays (EIA) for measles IgG and measles IgM. RESULTS: Among primary vaccinees, 14 of 19 infants aged 6 months (74%) developed NT antibody, as did 15 of 15 infants aged 15 months (100%). The reciprocal geometric mean titer of 6-month-old seroresponders was 23.3, significantly lower than that of the 15-month-old primary vaccinees (87.7, P < .001). Primary seroconversion rates by EIA were 53% for 6-month-old infants and 100% for those aged 15 months. Revaccination of infants who had received Attenuvax at 6 months of age resulted in 100% NT positivity; the geometric mean titer rose to equal that of the group given primary immunization at 15 months of age. Measles IgM antibody was detected in 10 of 14 infants tested 1 month after primary vaccination at 15 months, but was not detected in any of the revaccinated infants after the second dose at 15 months of age (P < .001). CONCLUSIONS: 1) Immunization with measles vaccine in infants born to vaccine-immune mothers at 6 months of age induced NT antibody in 74% of infants. 2) Revaccination of prior 6-month-old vaccinees at 15 months resulted in antibody titers equivalent to 15-month-old vaccinees. 3) Lack of an IgM response following revaccination suggests that even seronegative infants may be primed to respond on re-exposure to measles.

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

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

Selenium status of term infants fed human milk or selenite-supplemented soy formula.

Infants fed a soy formula supplemented with selenite had plasma and erythrocyte selenium values lower than those of infants fed human milk. However, plasma and erythrocyte glutathione peroxidase activities were normal, indicating that the physiologic requirement for selenium was being met.

Measuring the comparative efficacy of antibacterial agents for acute otitis media: the "Pollyanna phenomenon".

In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success, (62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media. These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy: (1) tympanocentesis and culture before and during therapy (bacteriologic efficacy), (2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media. For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media. For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media. We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are. The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media.

Selenium status of preterm infants fed human milk, preterm formula, or selenium-supplemented preterm formula.

The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.

Cefixime compared with amoxicillin for treatment of acute otitis media.

Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 mg/kg of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Streptococcus pneumoniae cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were H. influenzae (five cases, two beta-lactamase-positive), S. pneumoniae (one case), and Moraxella catarrhalis (one case, beta-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (1) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating H. influenzae otitis media and should be preferred when H. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent.

Host factors and early therapeutic response in acute otitis media.

To evaluate the relationship between eradication of bacterial infection and clinical improvement in children with otitis media, we reviewed the clinical outcome of bacterial otitis media in patients enrolled in double-blind trials of antibacterial therapy from 1979 to 1988. Cultures of middle ear exudates showed the distribution of bacterial pathogens to be similar to that observed in other geographic areas. Two hundred ninety-three patients had otitis media caused by bacterial pathogens and underwent repeat tympanocentesis after 3 to 6 days of therapy. Bacteriologic success was demonstrated in 253 patients (86%); 40 patients (14%) had bacteriologic failure. Children who had bacteriologic failure were younger than those with bacteriologic success (median age 10.6 vs 18.5 months; p = 0.001); 38% of patients who had bacteriologic failure were black, compared with 18% of patients with bacteriologic success (p = 0.007). Gender, history of frequent otitis media, and presence of bilateral otitis media were not risk factors for bacteriologic failure. Clinical success was demonstrated in 261 patients (89%); 32 patients (11%) had clinical failure. Agreement between clinical and bacteriologic response was 86% (95% confidence interval: 81.6% to 89.6%). Ninety-three percent (236/253) of subjects whose infection was eliminated had clinical resolution, whereas 37% (15/40) of those with bacteriologic failure had persisting symptoms or signs of clinical failure. We conclude that failure to eliminate bacteria from the middle ear is often associated with persistent signs and symptoms. Bacteriologic failure affects children less than 18 months of age almost exclusively. Bacteriologic and clinical failure are frequently discordant; mechanisms unrelated to the bacterial infection may explain some of the persisting clinical signs.

Early recurrences of otitis media: reinfection or relapse?

In a prospective study, 36 (35%) of 103 patients had early recurrence of acute otitis media. We wished to identify risk factors for early recurrences (those recurring within 1 month of initial diagnosis) and to determine if the second episode was caused by the same pathogen (relapse) or a new organism (reinfection). When the same bacterial species was recovered in both episodes, Streptococcus pneumoniae were serotyped and Haemophilus influenzae were classified by biotypes and by electrophoretic pattern of the outer membrane proteins. Twenty-nine patients underwent tympanocentesis at the time of the recurrent episode. In 13, no pathogen was recovered either initially or at the time of recurrence. Twelve (75%) of the remaining 16 patients had reinfection; only four (25%) had relapse. Thus, early recurrences of acute otitis media were more often caused by a new organism. This finding suggests that underlying susceptibility to middle ear infection is important in the development of recurrent otitis media. Pediatricians should not assume that early recurrences are necessarily the result of failure of initial treatment. Tympanocentesis may be helpful in this setting to aid in choosing appropriate antibiotic therapy.

A randomized controlled trial of amoxicillin plus clavulanate compared with cefaclor for treatment of acute otitis media.

We performed a randomized controlled trial of amoxicillin plus clavulanate versus cefaclor for treatment of acute otitis media. Total daily doses given in three divided doses were 40 mg/kg amoxicillin plus 10 mg/kg clavulanate, and 40 mg/kg cefaclor. Pathogens were eradicated from the middle ear exudate after 3 to 6 days of therapy in 35 (97%) of 36 patients given amoxicillin-clavulanate compared with 24 (75%) of 32 given cefaclor (P = 0.028). When analysis was restricted to patients with positive urine or serum drug assays during therapy, pathogens were eliminated in 33 (97%) of 34 patients given amoxicillin-clavulanate compared with 21 (75%) of 28 given cefaclor (P = 0.026). Bacterial isolates associated with bacteriologic failure of cefaclor therapy were Streptococcus pneumoniae (two patients), beta-lactamase-negative Haemophilus influenzae (four), and beta-lactamase-positive Branhamella catarrhalis (two). The single failure with amoxicillin-clavulanate therapy was associated with non-beta-lactamase-producing H. influenzae isolated from the middle ear exudate. We conclude that cefaclor is less efficacious than amoxicillin-clavulanate for the treatment of acute otitis media.

Objective diagnosis of otitis media in early infancy by tympanometry and ipsilateral acoustic reflex thresholds.

Otitis media in early infancy carries a high risk of recurrent otitis media and prolonged middle ear effusion. To fulfill the need for objective diagnostic methods in this age group, we investigated susceptance tympanograms and ipsilateral acoustic reflex thresholds in infants younger than 5 months of age. Tympanometry and acoustic reflex thresholds were performed with an otoadmittance meter using a 660 Hz probe tone. Tympanograms were interpreted using quantitative measures. These findings were compared with independent otoscopic diagnoses in 67 ears with middle ear effusion and 69 ears that were effusion free. Diagnoses were confirmed by tympanocentesis when clinically indicated. There was excellent agreement among otoscopy, peak tympanogram susceptance, and ipsilateral acoustic reflex thresholds (kappa 0.82 to 0.86, agreement 91% to 93%). We conclude that susceptance tympanograms and ipsilateral acoustic reflex thresholds are accurate diagnostic tests for otitis media in infants younger than 5 months of age.

A randomized controlled trial of cefaclor compared with trimethoprim-sulfamethoxazole for treatment of acute otitis media.

We performed a randomized controlled trial of cefaclor administered twice daily compared with trimethoprim-sulfamethoxazole (TMP-SMZ) administered twice daily for the treatment of acute otitis media. Pathogens were eradicated from the middle ear exudate after 3 to 6 days of therapy in 35 of 37 (95%) patients given TMP-SMZ compared with 28 of 40 (70%) given cefaclor (P = 0.017). Haemophilus influenzae was eliminated in 13 of 14 (93%) patients given TMP-SMZ compared with 10 of 18 (56%) given cefaclor (P = 0.047). Clinical outcomes failed to distinguish between patients given TMP-SMZ or cefaclor. Symptoms improved despite persistent infection in 11 of 13 (85%) patients; middle-ear effusion persisted after therapy in 38 of 61 (62%) patients despite eradication of pathogens. We conclude that twice daily TMP-SMZ is more efficacious than twice daily cefaclor for the treatment of acute otitis media and that clinical outcomes may fail to detect differences between antibacterial agents in comparative drug trials in acute otitis media.

Mortality of Dipetalogaster maximus (uhler) in response to temperature and humidity.

Observou-se a mortalidade do Dipetalogaster maximus em relacao a temperatura e umidade, em condicoes controladas. Os triatomineos sobreviveram maior tempo em umidades relativas mais altas e em temperaturas mais baixas, mas quando estes resultados foram distribuidos graficamente em con dicoes de baixa pressao, nenhum efeito foi visto, independentemente da variacao de temperatura. O resultado pode ser explicado pela evaporacao mais rapida de agua nas condicoes de baixa pressao. O D. maximus nao aumenta sua resistencia quando se injeta vapor de agua em ambientes de baixa pressao. Para aumentar a sobrevida do D.maximus quando usado para xenodiagnostico em condicoes de campo e conviniente protege-lo das altas temperaturas e baixas umidades