Prevalence of hepatitis B surface antigen in vaccinated children and controls in rural Nigeria.

OBJECTIVE: To determine the prevalence of hepatitis B surface antigen (HBsAg) amongst vaccinated children and controls aged 1-4 years in a rural community in mid-western Nigeria. METHODS: The vaccinated children had received at least three doses of hepatitis B vaccine. The vaccines included recombinant hepatitis B vaccine at birth and a combined diphtheria, tetanus, pertussis (whole cell) plus hepatitis B (DTPw-HBV) vaccine. HBsAg was determined by a rapid immunoassay method based on the immunochromatographic sandwich principle. Two hundred and twenty-three children and 219 controls were recruited into the study. RESULTS: The prevalence of HBsAg was significantly lower in the vaccinated group (1.3%) than in the control group (4.6%, p=0.04). The prevalence rates were significantly higher in males (p=0.02) and two-year birth cohort (p=0.01). The controls were estimated to be at a six-fold higher risk of being positive for the surface antigen than the vaccinated children. The vaccine effectiveness was estimated to be approximately 80%. CONCLUSION: These results confirm that hepatitis B vaccine protects against hepatitis B surface antigen carriage and confirm immunogenicity of the combined DTPw-HBV vaccine.

Short term evaluation of a rural immunization program in Nigeria.

BACKGROUND: Immunization remains the primary strategy in both the control and prevention of common childhood diseases, particularly in the developing world. Immunization and preprimary health care services were commenced in a rural community in Nigeria in 1998, when vaccine coverage for all Expanded Program on Immunization (EPI) diseases (tuberculosis, polio, diphtheria, pertussis, tetanus, measles, and hepatitis B) was considerably low with only 43% of children fully immunized. METHODS: Children aged 0-2 years and living in a rural community were recruited into the study. Data on vaccination history was collected by both vaccination card and maternal history. Three hundred and twenty-seven children were recruited into the study. Study participants were vaccinated for EPI diseases. Hepatitis-B vaccine was administered at birth, and a combined diphtheria and tetanus toxoids, and pertussis whole cell vaccine (DTP) plus hepatitis-B vaccine was administered in a single injection after six weeks. RESULTS AND CONCLUSIONS: Two years after the program was started, immunization coverage rates were 94% for BCG, 88% for DTP (third dose), and 82% for measles. All antigens showed significant improvements from baseline values (p < 0.0001). Eighty four percent of children were fully immunized against all six diseases, compared with 43% at the commencement (p < 0.0001). Hepatitis-B coverage (three doses) was 58%. The vaccination program has significantly improved vaccination coverage and could be a model for under served, non-industrialized communities.

Safety and immunogenicity of Haemophilus influenzae type B-Neisseria meningitidis group B outer membrane protein complex conjugate vaccine mixed in the syringe with diphtheria-tetanus-pertussis vaccine in young Gambian infants.

To ensure compliance and to reduce costs it is important, especially in less developed countries, that programs of child immunization should require as few clinic attendances and as few injections as possible. Therefore we have investigated whether a Haemophilus influenzae type b conjugate vaccine could be given safely and effectively with diphtheria-tetanus-pertussis vaccine (DTP). One hundred twenty-six Gambian infants were given both polyribosylribitol phosphate (PRP)-outer membrane protein complex (PedvaxHIB) and DTP on the same day at 8, 12 and 16 weeks of age; 60 were given the vaccines mixed in the syringe and 66 were given the vaccines separately. To minimize the injection volume the dose of PRP-OMPC used in both groups was 7.5 micrograms, which is half the usual dose. There were no significant differences in anti-PRP antibody titers between the groups after 1, 2 or 3 doses. The geometric mean titers of antibody for the two groups combined were 0.29 micrograms/ml 1 month after the first dose, 1.03 micrograms/ml after the second dose and 1.11 micrograms/ml after the third dose. Concentrations of antibodies to diphtheria, tetanus and pertussis 1 month after the third dose were not significantly different between the two groups. Systemic side effects were reported with equal frequency in the two groups and were similar to those reported elsewhere for DTP. Tenderness at the injection site was more common where the combined injection (0.75 ml) had been given than where DTP alone (0.5 ml) had been given. The main drawback to the use of these 2 vaccines together is the complexity of the mixing procedure used in this clinical trial.

Persistence of antibody at 18 months following vaccination of young Gambian infants with PRP-OMPC Haemophilus influenzae type b conjugate vaccine.

The rate of decline in anti-PRP antibody levels was measured in two groups of Gambian children who had been given PRP-OMPC at 1 and 3 months or 2 and 4 months of age. In the younger group (n = 70), the geometric mean titre fell from 1.32 micrograms/ml at 4 months to 0.44 micrograms/ml at 18 months. In the older group (n = 54), the geometric mean titre fell from 1.18 micrograms/ml at 5 months to 0.46 micrograms/ml at 18 months. The proportion of vaccinated children with antibody levels over 1.0 microgram/ml fell from 54% 1 month after the second dose of vaccine to 27% at the age of 18 months, while the proportion with levels over 0.15 micrograms/ml fell from 82% to 60%, with no significant differences observed between the vaccination groups. For those children who did not show evidence of environmental boosting, the half-life of anti-PRP antibody was about 100 days. This did not differ between the groups. These findings suggest that to provide lasting immunity PRP-OMPC should be given with a late booster dose at 12-15 months, as is the current practice in the USA. The need for a late booster dose may limit the value of this vaccine in developing countries where vaccination of children is difficult after the 1st year of life.

Clinical experience with PedvaxHIB, a conjugate vaccine of Haemophilus influenzae type b polysaccharide--Neisseria meningitidis outer membrane protein.

PedvaxHIB, a Haemophilus influenzae type b (Hib) conjugate vaccine composed of Hib capsular polysaccharide covalently bound to an outer membrane protein complex of Neisseria meningitidis serogroup B, was evaluated for immunogenicity and safety in infants and children 2 months of age and older. A significant and consistent antibody response was seen after a single dose of the vaccine in all age groups, including infants as young as 2 months of age. In addition, the vaccine elicited a good booster response when given at 12 to 17 months of age. Subjects from diverse subpopulations, including those with impaired antibody response to Hib polysaccharide vaccines, showed a significant response to vaccination. The vaccine was well tolerated when administered alone or concurrently with other paediatric vaccines. A protective efficacy study, recently completed, has shown the vaccine to be highly effective in 2-month-old infants.

An enzyme-linked immunosorbent assay for quantitation of Haemophilus Influenzae type b polysaccharide-specific IgG1 and IgG2 in human and infant rhesus monkey sera.

An enzyme-linked immunosorbent assay (ELISA) has been developed and validated to quantitate IgG1 and IgG2 antibody to polyribosyl-ribitol phosphate (PRP), the capsular polysaccharide of Haemophilus influenzae type b (Hib). The sera of children and infant Rhesus monkeys immunized with an Hib conjugate vaccine composed of Hib PRP covalently linked to an outer membrane protein complex (OMPC) from Neisseria meningitidis serogroup B (PedvaxHIB, PRP-OMPC, Merck, Sharp and Dohme Research Laboratories). The solid-phase antigen employed in the ELISA is a conjugate of PRP to human serum albumin. The enzyme-labeled antibody is alkaline phosphatase-conjugated mouse monoclonal (mAb) anti-human IgG1 or IgG2. A human serum standard was calibrated using parallel titrations with a known antibody standard. The geometric mean titer (GMT) of the anti-PRP IgG1 response to one dose of PedvaxHIB was 3.87 micrograms/ml (n = 82), 11.80 micrograms/ml (n = 62) and 14.57 micrograms/ml (n = 74) in infants and children 12 to 17 months, 18 to 23 months and greater than or equal to 24 months old, respectively. Infants 2 to 11 months old responded with an IgG1 anti-PRP response of 7.10 micrograms/ml while infant monkeys responded with a GMT of 150.65 (n = 9) after two doses of vaccine. The anti-PRP IgG2 GMT responses in all groups were less than 0.25 micrograms/ml, except for humans greater than or equal to 18-months old who exhibited a GMT of greater than or equal to 0.40 micrograms/ml (n = 75). PedvaxHIB, immunization of human infants and children and infant Rhesus monkeys elicits primarily an IgG1 response to PRP. The monkey model appears to be a reliable indicator of the human immune response.

Serologic responses to an Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in very young Gambian infants.

Recent studies in the United States and Europe have shown that Haemophilus influenzae type b polysaccharide-protein conjugate vaccines can induce protective antibody levels in young infants, but it was not clear that this would be the case in African infants, to whom H influenzae vaccines must be given at a very early age to prevent disease caused by H influenzae. Therefore, antibody responses to an H influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine were measured in very young Gambian infants. In the first group (n = 85), to whom the vaccine was given at the ages of 1 and 3 months, the geometric mean antibody level rose from a prevaccination level of 0.23 microgram/mL to a postvaccination level of 1.27 micrograms/mL, and in the second group (n = 56), vaccinated at the ages of 2 and 4 months, the prevaccination level of 0.16 microgram/mL rose to a postvaccination level of 1.59 micrograms/mL. These two final postvaccination levels did not differ significantly, and interpolation suggests that similar antibody levels were present in both groups of infants at the age of 3 months. This is the age by which protection would need to be achieved to protect against H influenzae meningitis in The Gambia and in other countries where the infection has similar epidemiologic characteristics. No significant side effects of vaccination were noted.

Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB): clinical evaluation.

Although systemic infections caused by Haemophilus influenzae type b occur worldwide, detailed epidemiologic data are available in but a few countries. The public health impact of morbidity, mortality, and serious sequelae from disease caused by H influenzae type b has stimulated the search for control strategies. In the United States now, active immunoprophylaxis is largely favored over treatment of prophylaxis with antibiotics. This preference stems from three major observations: that high mortality and morbidity persist despite the availability of potent antimicrobial agents, that antibiotic-resistant strains of H influenzae type b have emerged, and that implementation of antimicrobial prophylaxis on a large scale has been unsatisfactory. Moreover, universal vaccination has been projected as offering a higher economic benefit than other control strategies. A matter of more proximate importance, however, is the search for H influenzae type b vaccines that will confer protection to all age groups, including infants younger than 18 months of age and subpopulations specifically at risk for invasive disease caused by H influenzae type b. Haemophilus b conjugate vaccine (meningococcal protein conjugate), PedvaxHIB (PRP-OMPC), is a conjugate H influenzae type b vaccine developed at Merck Sharp & Dohme Research Laboratories that now is undergoing extensive clinical evaluation to assess its prospects for disease control when first administered in early infancy. This is an interim report of results obtained in studies conducted in diverse locations throughout the United States.

Imipenem-cilastatin in pediatric patients: an overview of safety and efficacy in studies conducted in the United States.

Imipenem-cilastatin was evaluated for tolerability and efficacy in a multicenter open, noncomparative trial involving 178 infants and children with bacterial infections. Imipenemcilastatin was administered in total daily dosages of 100 mg/kg for patients up to 3 years of age and 60 mg/kg for those more than 3 years of age. Favorable clinical response was achieved in 98 of 100 patients judged evaluable for efficacy. Adverse effects were generally mild and reversible and included diarrhea alone or with vomiting (5.1%), irritation of intravenous infusion site (3.3%) and rash (2.2%). Changes in laboratory test values reported most frequently were thrombocytosis (8.9%), elevations in aspartate aminotransferase (7.9%) and alanine aminotransferase (5.6%) and eosinophilia (8.4%). This safety profile appears to be comparable to that of other beta-lactam antibiotics. Moreover imipenem-cilastatin was effective in infections caused by a broad spectrum of pathogens that include Haemophilus influenzae, Staphylococcus aureus, P. aeruginosa and anaerobes. These attributes suggest that imipenem-cilastatin should be safe and effective in selected pediatric patients.

In-vitro activity of imipenem against 100 strains of serotype b and nontypable Haemophilus influenzae, including strains resistant to ampicillin, chloramphenicol or both.

Imipenem, along with ampicillin, chloramphenicol, ceftazidime, aztreonam and ceftriaxone were tested against 100 clinical isolates of Haemophilus influenzae. Eighty-eight of the isolates were serotype b, 35 isolates were beta-lactamase producers, and five isolates were chloramphenicol resistant. Inoculum densities of 1 X 10(3), 1 X 10(5) and 1 X 10(8) cfu/ml were tested for all isolates. MIC90s and MBC90s at the two lower inoculum densities for imipenem, ceftazidime, aztreonam and ceftriaxone were in the susceptible range for all categories of isolates tested. Imipenem, ceftazidime and aztreonam displayed elevated MBC90s at the high inoculum density. The effect of the high inoculum density upon the ceftriaxone MBC90 was below the level of detection afforded by the study design.

Review of adverse experiences and tolerability in the first 2,516 patients treated with imipenem/cilastatin.

The clinical and laboratory data relating to the adverse experiences and tolerability of imipenem/cilastatin in the first 2,516 patients treated with the antibiotic are reviewed, with special reference to the last 793. Clinical adverse experiences were predominantly related to the gastrointestinal system (nausea and vomiting), local injection site, and allergy (rash). A low frequency of drug-related seizures was also reported. The most frequent adverse laboratory experiences were transient elevations of liver function test values. In general, the safety profile was similar to that of other beta-lactam antibiotics.

Acute cervical lymphadenitis in hospitalized pediatric patients: predominance of Staphylococcus aureus in infancy.

Sixty-one cases of acute cervical lymphadenitis in Kings County Hospital Center were reviewed. Staphylococcus aureus accounted for 50 percent of the cases and Group A ß-hemolytic streptococcus accounted for 15 percent; 35 percent had no growth on culture. Of the variables considered (age, sex, temperature, leukocytosis, previous antibiotic treatment, duration of symptoms, lymph node consistency) only age appeared to be a predictor of the causative organisms. Children under 1 year of age had a higher incidence of S aureus (65 percent) than children above 3 years of age (25 percent); the difference was statistically significant (P <.01). Therapeutic antimicrobial regimens should include coverage for S aureus in this age group.

Haemophilus influenzae septic thrombophlebitis following use of a "scalp-vein" needle.

Indolent Haemophilus influenzae type B septic thrombophlebitis developed in a 14-year-old boy two weeks after completing a course of intravenous antibiotics administered via a "scalp-vein" needle for an unrelated infection. Presumably, the primary disease (common variable immunodeficiency) contributed to the simultaneous occurrence of this uncommon complication of scalp-vein needle use, with an unusual pathogen.

Urinary tract infection in infants with unexplained fever: a collaborative study.

Nine centers collaborated to determine the rate of urinary tract infection in infants with unexplained fever, to determine whether the rate is higher in febrile infants than in asymptomatic infants, and whether the yield justifies urine cultures in febrile infants. Urine cultures were done in 501 infants 0 to 2 years of age. The rate of confirmed urinary tract infections in the 193 febrile infants was 4.1%. All infections were in girls, with a rate of 7.4%. The rate of confirmed urinary tract infections in the 312 asymptomatic infants was 0.3%; again, all infections were in girls, with a rate of 0.7%. The rate in febrile girls was significantly higher than the rate in asymptomatic girls (P less than 0.01). The data support the advisability of culturing the urine of infant girls with unexplained fever.

In vitro activity of cefodizime (HR-221).

The in vitro activity of cefodizime (HR-221), a new cephalosporin antibiotic, was compared with the activities of selected antimicrobial agents against a broad spectrum of aerobic bacteria. Cefodizime concentrations of 2 micrograms/ml inhibited about 90% of Enterobacteriaceae studied. Serratia marcescens required 8 micrograms/ml to inhibit 90% of strains. Among gram-positive cocci, 50% of strains were inhibited by 2 micrograms/ml of cefodizime (including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, and penicillin-resistant Streptococcus pneumoniae). Pseudomonas aeruginosa was less susceptible to cefodizime. Cefotaxime, an antibiotic closely related to cefodizime structurally, was about fourfold more active.

Comparative in vitro activities of cefmenoxime (SCE-1365) and newer cephalosporin derivatives of clinical utility.

The minimal inhibitory concentrations of cefmenoxime (SCE-1365), cefotaxime, cefoperazone, and moxalactam against various species of aerobic bacteria were determined. The activities of cefmenoxime, cefotaxime, and moxalactam were generally similar and slightly higher than the activity of cefoperazone.

In vitro activity of U-57930E, a new clindamycin analog, against aerobic gram-positive bacteria.

The in vitro activity of U-57930E, a new clindamycin analog, against aerobic gram-positive cocci was studied by microdilution broth susceptibility tests and compared with the activities of clindamycin, vancomycin, oxacillin, and ampicillin. U-57930E inhibited methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus viridans at concentrations of less than or equal to 1 microgram/ml. This degree of activity was generally slightly less than that of the other antimicrobial agents tested. Methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci, penicillin-resistant Streptococcus pneumoniae, and enterococci were resistant to U-57930E. At the concentrations used, U-57930E exhibited bactericidal activity against most susceptible organisms, and a minimal effect of inoculum size was noted.

Infections in children with sickle cell anemia. Special reference to pneumococcal and salmonella infections.

Pneumococcal sepsis and/or meningitis are major causes of morbidity and mortality in young children with sickle cell disease. Abnormal complement activity, poor splenic function and a lack of type-specific pneumococcal antibody are responsible for the severity and frequency of these infections. A program consisting of early institution of antibiotic therapy for febrile episodes, antimicrobial prophylaxis, and administration of pneumococcal vaccine may be effective in reducing the incidence of pneumococcal disease. Specific guidelines for infection prevention are presented. Other infections that are more frequent or more severe in children with sickle cell disease (e.g., Salmonella, Haemophilus and mycoplasma infections) are also discussed.

In vitro susceptibility of Campylobacter fetus subsp. jejuni to N-formimidoyl thienamycin, rosaramicin, cefoperazone, and other antimicrobial agents.

The activities of 11 antimicrobial agents against 36 strains of Campylobacter fetus subsp. jejuni were studied by a broth microdilution method. All strains were susceptible to 7 of the 11 antimicrobial agents. Of the newer agents tested N-formimidoyl thienamycin (MK0787) and rosaramicin had very good activity, whereas cefotaxime, moxalactam, and cefoperazone had poorer activity.