Functional antibody activity elicited by fractional doses of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate).

We evaluated the functional activities of antibodies, serum bactericidal activity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using sodium thiocyanate (NaSCN) elution, elicited after vaccination with fractional doses of the Haemophilus influenzae type b conjugate (polyribosylribitol phosphate [PRP] conjugated to tetanus toxoid [PRP-T]) vaccine. A cohort of 600 infants from the Dominican Republic were randomized to receive one of three regimens of the PRP-T vaccine at ages 2, 4, and 6 months: full doses (10 microg of PRP antigen), one-half doses (5.0 microg), and one-third doses (3.3 microg) (J. Fernandez et al., Am. J. Trop. Med. Hyg. 62:485-490, 2000). Sixty serum samples, collected at age 7 months, with > or =2.0 microg of anti-PRP IgG per ml were randomly selected for avidity determinations. Geometric mean IgG concentrations were 13, 14, and 17 microg/ml for infants who received the full-dose (n = 19), one-half-dose (n = 19), and one-third-dose (n = 22) regimens, respectively. SBA geometric mean titers (1/dilution) were 85.0, 82.0, and 76.1 in sera from infants receiving the full-, one-half-, and one-third-dose regimens, respectively. Avidity indices (mean +/- standard error weighted average of NaSCN molar concentration x serum dilution factor) were 71.9 +/- 9.4, 123.6 +/- 26.8, and 150.9 +/- 24.9 for the full-, one-half-, and one-third-dose regimens, respectively. Upon comparison, the only significant difference (P = 0.024) found was a greater avidity index for sera from infants receiving the one-third-dose regimen than for sera from infants receiving the the full-dose regimen. We conclude that fractional doses elicit similar functional antibody activities in infants with > or = 2 microg of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants receiving three doses of either the full concentration or one-half or one-third of the labeled concentration, respectively. This approach offers an alternative strategy for the prevention of H. influenzae type b disease in countries with limited resources.

Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial.

CONTEXT: Emerging drug resistance threatens the effectiveness of existing therapies for pneumococcal infections. Modifying the dose and duration of antibiotic therapy may limit the spread of resistant pneumococci. OBJECTIVE: To determine whether short-course, high-dose amoxicillin therapy reduces risk of posttreatment resistant pneumococcal carriage among children with respiratory tract infections. DESIGN AND SETTING: Randomized trial conducted in an outpatient clinic in Santo Domingo, Dominican Republic, October 1999 through July 2000. PARTICIPANTS: Children aged 6 to 59 months who were receiving antibiotic prescriptions for respiratory tract illness (n = 795). INTERVENTIONS: Children were randomly assigned to receive 1 of 2 twice-daily regimens of amoxicillin: 90 mg/kg per day for 5 days (n = 398) or 40 mg/kg per day for 10 days (n = 397). MAIN OUTCOME MEASURES: Penicillin-nonsusceptible Streptococcus pneumoniae carriage, assessed in nasopharyngeal specimens collected at days 0, 5, 10, and 28; baseline risk factors for nonsusceptible pneumococcal carriage; and adherence to regimen, compared between the 2 groups. RESULTS: At the day 28 visit, risk of penicillin-nonsusceptible pneumococcal carriage was significantly lower in the short-course, high-dose group (24%) compared with the standard-course group (32%); relative risk (RR), 0.77; 95% confidence interval (CI), 0.60-0.97; P =.03; risk of trimethoprim-sulfamethoxazole nonsusceptibility was also lower in the short-course, high-dose group (RR, 0.77; 95% CI, 0.58-1.03; P =.08). The protective effect of short-course, high-dose therapy was stronger in households with 3 or more children (RR, 0.72; 95% CI, 0.52-0.98). Adherence to treatment was higher in the short-course, high-dose group (82% vs 74%; P =.02). CONCLUSION: Short-course, high-dose outpatient antibiotic therapy appears promising as an intervention to minimize the impact of antibiotic use on the spread of drug-resistant pneumococci.

Prevention of Haemophilus influenzae type b colonization by vaccination: correlation with serum anti-capsular IgG concentration.

Concentrations of serum anti-Haemophilus influenzae type b (anti-Hib) capsular polysaccharide (CPS) >/=0.15 and >/=1.0 microgram/mL are widely used as surrogates for protection against invasive Hib disease. However, the relationship between serum anti-Hib CPS following immunization and protection against colonization is not known, making it difficult to evaluate new Hib vaccines or combination vaccines. In the Dominican Republic, nasopharyngeal swabs were collected from 546 9-month-old infants who had received Hib conjugate vaccine at ages 2, 4, and 6 months and from 600 unvaccinated infants of the same age. The prevalence of Hib colonization was lower among vaccinated infants than among unvaccinated infants (0.9% vs. 2.3%). Among vaccinated infants, protection against colonization was significantly correlated with anti-Hib CPS concentrations >/=5 microgram/mL 1 month following the third dose of vaccine. These results suggest that the concentration of serum anti-Hib CPS needed for protection against colonization is greater than that needed for protection for invasive disease.

Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media.

OBJECTIVES: To compare the bacteriologic and clinical efficacy of amoxicillin/clavulanate and azithromycin in patients with acute otitis media (AOM), particularly the ability to eradicate the predominant AOM pathogens from middle ear fluid as assessed by mandatory second tympanocentesis. METHODS: In this single blind study 238 infants and children with AOM were randomized to receive amoxicillin/clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or azithromycin (10 mg/kg on Day 1, then 5 mg/kg daily on Days 2 through 5). Tympanocentesis was performed before the first dose and repeated on Day 4, 5 or 6. Clinical response was assessed at end of therapy between Days 12 and 14 and at follow-up between Days 22 and 28. RESULTS: Amoxicillin/clavulanate was significantly more likely to eradicate all bacterial pathogens [83% (54 of 65) vs. 49% (35 of 71), P = 0.001] and Haemophilus influenzae [87% (26 of 30) vs. 39% (13 of 33), P = 0.0001] from middle ear fluid than was azithromycin. Amoxicillin/clavulanate was also more likely to eradicate Streptococcus pneumoniae, but the difference was not statistically significant [90% (18 of 20) vs. 68% (13 of 19) [corrected], P = 0.095]. On Days 12 to 14, signs and symptoms were more likely to resolve completely or improve in all culture-positive patients [86% (60 of 70) vs. 70% (51 of 73), P = 0.023] and in those with H. influenzae infections [91% (30 of 33) vs. 65% (22 of 34), P = 0.010] who received amoxicillin/clavulanate compared with those who received azithromycin. Otherwise there were no significant differences between groups in clinical outcomes on Days 12 to 14 or at follow-up. CONCLUSIONS: Our findings indicate that amoxicillin/clavulanate has superior bacteriologic and clinical efficacy compared with azithromycin in children with AOM.

Population-based surveillance for bacterial meningitis in the Dominican Republic: implications for control by vaccination.

Quantifying the local burden of disease is an important step towards the introduction of new vaccines, such as Haemophilus influenzae type b (Hib) conjugate vaccine. We adapted a generic protocol developed by the World Health Organization for population-based surveillance of bacterial meningitis. All hospitals that admit paediatric patients with meningitis in the National District, Dominican Republic were included in the system and standard laboratory methods were used. The system identified 111 cases of confirmed bacterial meningitis. Hib was the leading cause of bacterial meningitis, followed by group B streptococcus, S. pneumoniae, and N. meningitidis. Unlike hospital-based case series, this population-based system was able to calculate incidence rates. The incidence of Hib meningitis was 13 cases per 100,000 children < 5 years old. The data from this study were used by the Ministry of Health to support the introduction of routine Hib vaccination and will be used to monitor its effectiveness.

Randomized trial of the immunogenicity of fractional dose regimens of PRP-T Haemophilus influenzae type b conjugate vaccine.

To assess the immunogenicity of more economical regimens of Haemophilus influenzae type b (Hib) conjugate vaccine, a randomized trial of fractional doses of polyribosylribitol phosphate-tetanus toxoid (PRP-T) Hib vaccine was undertaken in the Dominican Republic. Six hundred children were assigned to one of six regimens with PRP-T vaccine: full-dose, half-dose, and one-third-dose of Hib vaccine given separately or combined with diphtheria, tetanus, and pertussis (DTP) vaccine at ages 2, 4, and 6 months. Regimens that elicited antibody levels > 1.0 microg/mL in >70% of children and < or = 0.15 microg/mL in > 90% of children were considered acceptable. At 1 month post Dose 3, all regimens met the criteria for acceptable response. Among those who received Hib as a separate injection, geometric mean concentrations of anti-PRP bodies (GMCs) at age 1 month post Dose 3 were 11.2, 11.9, and 16.3 in the full, half, and one-third dose groups, respectively. Among those who received Hib and DTP combined, the GMCs were 6.4, 5.2, and 5.7 in the full-, half-, and one-third-dose groups respectively.

Prospective, randomized, investigator-blinded study of the efficacy and safety of meropenem vs. cefotaxime therapy in bacterial meningitis in children. Meropenem Meningitis Study Group.

OBJECTIVES: To compare the efficacy and safety of meropenem with cefotaxime for the treatment of infants and children with bacterial meningitis. METHODS: Infants and children with strongly suspected or documented bacterial meningitis were randomly assigned in a prospective multicenter study to receive either meropenem or cefotaxime. Patients were assessed at the end of therapy and at 5 to 7 weeks and 5 to 7 months after the end of treatment for the presence of neurologic and sensory neural sequelae. RESULTS: A total of 258 children were randomized to either treatment group. A further 8 patients with suspected pneumococcal meningitis were treated with meropenem without randomization. Of the randomized patients 154 were fully evaluable, 79 in the meropenem group and 75 in the cefotaxime group. At the end of treatment there were no significant differences in clinical outcome between the two treatment groups. Clinical cure with or without sequelae was achieved in 97 and 96% of the meropenem- and cefotaxime-treated patients, respectively. At the end of treatment and at 5 to 7 weeks, 46 and 54% of meropenem patients were cured with no sequelae, respectively. Corresponding results for cefotaxime patients were 56 and 58%. All pathogens were eradicated. In total 37 patients had seizures during treatment, 15 (12%) in the meropenem and 22 (17%) in the cefotaxime group. None of the seizures was considered to be drug-related. CONCLUSIONS: This trial shows that meropenem is suitable therapy for bacterial meningitis in infants and children and that it offers an efficacy and safety profile similar to that of cefotaxime.

The epidemiology of Haemophilus influenzae type b carriage among infants and young children in Santo Domingo, Dominican Republic.

BACKGROUND: Whether herd immunity will occur with widespread Haemophilus influenzae type b (Hib) vaccination in developing countries is dependent on whether the vaccines are capable of reducing carriage in these settings. However, few population-based studies of Hib carriage in developing countries exist. METHODS: To study Hib carriage in the Dominican Republic, we collected nasopharyngeal swab specimens from a population-based sample of 983 children 0 to 47 months old in a periurban area of Santo Domingo. RESULTS: Nasopharyngeal swabs of 76 (7.7%) children were positive for Hib. Hib carriage varied by age group with a low of 1.5% among 0 to 5 month olds, a peak of 12.5% in 6 to 11 month olds and prevalence rates of 6.0, 7.9 and 9.8% among 1-, 2- and 3-year-olds, respectively. Hib carriage was 51% lower among currently breast-fed 6 to 11 month olds than among those not currently breast-fed (18.2% vs. 9.0%; P=0.08). CONCLUSIONS: Infants and young children in Santo Domingo have high rates of Hib carriage, characterized by an early peak in carriage that corresponds with the peak of risk for Hib meningitis. The ability of Hib vaccines to diminish carriage to levels that will effectively reduce transmission and lead to herd immunity in this setting needs to be determined.

Comparison of oral cefuroxime axetil and oral amoxycillin/clavulanate in the treatment of community-acquired pneumonia.

Cefuroxime axetil has been evaluated previously in the treatment of lower respiratory tract infections, but not specifically in the treatment of community-acquired pneumonia. In a multicentre, investigator-blinded clinical trial, 162 patients with community-acquired pneumonia were randomly assigned to receive orally either cefuroxime axetil 500 mg bid (n = 84) or amoxycillin/clavulanate 500 mg/125 mg tid (n = 78) for 10 days. Organisms were isolated from the pretreatment sputum specimens of 97 of 162 (60%) patients, the commonest isolates being Streptococcus pneumoniae (38%) and Haemophilus influenzae (18%). A satisfactory clinical outcome (cure or improvement) was achieved in 100% (55 of 55) and 96% (49 of 51) of the clinically evaluable patients treated with cefuroxime axetil or amoxycillin/clavulanate, respectively (P = 0.23). With respect to eradication of bacterial pathogens, a satisfactory outcome (cure, presumed cure or cure with colonization) was obtained in 94% (32 of 34) and 93% (37 of 40) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxycillin/clavulanate, respectively (P = 1.00). Both treatment regimens used in this study were well tolerated. The most common drug-related adverse experiences were gastrointestinal events, reported by 8% and 4%, respectively, of the patients in the amoxycillin/clavulanate and cefuroxime axetil groups, a difference which was not statistically significant (P = 0.32). These results indicate that cefuroxime axetil twice a day is as effective as amoxycillin/clavulanate three times a day in the treatment of outpatients with mild to moderate community-acquired pneumonia.

Tumores farmacoinducidos por anovulatorios

Presentamos la casuística de tumores hepáticos farmacoinducidos por anovulatorios en nuestra área geográfica. Del total de 42 pacientes con tumores de hígado, en 4 casos (10 por ciento) se detectaron neoplasias en mujeres jóvenes que estaban usando anticonceptivos. Se discuten algunos aspectos patogénicos y diagnósticos

Enfermedades hepáticas. Estudio etiológico

Diseñamos un estudio prospectivo a dos años con el objetivo fundamental de establecer cuáles son las enfermedades hepáticas más frecuentes e identificar, en la medida de lo posible, los factores etiológicos en los distintos grupos de pacientes que consultan a la sala de urgencias de nuestro hospital. Estudiamos 68 pacientes, con biopsia hepática, predominando la infecciones, luego las neoplasias y la cirrosis

[Incidence of measles with complications]. / Incidencia de sarampion complicado.

PIP: Measles is caused by a virus which exclusively affects humans. Erroneously it has been considered benign, although it causes high morbidity and mortality because of the complications it precipitates. The Expanded Program of Immunization estimated that 1.5 million children in the world die every year because of measles. The objective was to analyze the incidence of measles and complicated measles in children who had been admitted to Dr. Robert Reid Cabral Pediatric Clinic, Santo Domingo, Dominican Republic, during the period of January 1991 to January 1992. A total of 311 patients were enrolled with the diagnosis of measles during the 13 months of the study, with an average of 24 cases per month. October and December were the months when most patients presented with measles: respectively, 56 (18%) and 60 (19.4%) patients of the total caseload. Pneumonia was the most frequent complication with 277 cases (87.1%), followed by acute diarrheal disease with 25 cases (8.0%). The most affected was the 1-3 year age group with 143 patients (46.0%). In 135 cases (43.4%) the children with measles had not been vaccinated; only 72 patients (23.3%) had received vaccination. Furthermore, 104 patients (33.3%) did not know their vaccination history. 170 patients (54.7%) were malnourished. During the study period 37 children (11.9%) died in the hospital and 24 of these children (64.9%) died as a result of the complication of pneumonia. Other causes of death were: laryngotracheitis (4), encephalitis (3), subcutaneous emphysema (4), and septicemia (2). This investigation showed that pneumonia is a very grave complication in malnourished children and in children under one year of age.^ieng

[Human immunodeficiency virus and hepatitis B virus in children transfused in the Dr. Luis Manuel Morillo King Hospital]. / Virus de inmunodeficiencia humana y hepatitis B en ninos transfundidos en el Hospital "Dr. Luis Manuel Morillo King".

PIP: The archives of the blood bank of the hospital of Dr. Louis Manual Morillo King, in the city of La Vega, Dominican Republic, were reviewed to identify all children who had been given blood transfusion during the period of July 1983 to July 1987 in order to identify HIV and the surface antigen of hepatitis B (HBsAg). Those who were released were visited in their homes for administration of HIV and hepatitis tests. Positive tests were confirmed by another test (AUSYME MONOCLONAL and Western Blot). Mothers were also tested to detect vertical transmission. 256 patients had been transfused, of whom 61 died. 80 of the 195 remaining patients could not be located. Of the 115 patients located, 52 had died in their homes after release from the hospital. Thus, the sample comprised 63 patients: 36 were 0-3 years old, 21 were 4-7 years old, and 6 were 8-11 years old. 50 lived in rural and 13 in urban areas. 56 patients had one transfusion and 4 had two transfusions. 28 patients had transfusion for anemia, 19 for malnutrition, 7 for sepsis, 6 for various reasons (meningitis, pleuritis, pneumonia), and 3 for sickle cell disease. 47 patients had been transfused at the hospital using the blood bank, 13 used blood from relatives, and 3 received blood from friends. Out of the 63 samples processed, 2 patients presented seropositivity for hepatitis B, while none were seropositive for HIV. Among the 2 patients who were seropositive for hepatitis B, the mother of one of them was also seropositive.^ieng

Treatment of Pseudomonas meningitis with ceftazidime with or without concurrent therapy.

In ongoing studies in Europe and the United States, 10 pediatric patients with bacterial meningitis caused by Pseudomonas species were treated with ceftazidime. Pseudomonas aeruginosa was isolated from the CSF of 7 patients and other Pseudomonas species from the remaining 3. Eight of the 10 patients had received previous antimicrobial treatment which included aminoglycosides in 6, along with ticarcillin and ureidopenicillins in 3. Ceftazidime was administered 10 to 42 days in dosages ranging from 109 to 300 mg/kg/day. Seven of the 10 patients received ceftazidime only for 10 to 42 days. The other 3 patients received amikacin in 2 and gentamicin and tobramycin in the other. Seven patients were cured clinically and 3 died; 9 were cured bacteriologically and one who was presumed cured on the basis of clinical response subsequently died. Sterilization of the cerebrospinal fluid occurred at 48 hours to 12 days. Ceftazidime appears useful in treating bacterial meningitis caused by Pseudomonas species.

Aztreonam in the treatment of gram-negative meningitis and other gram-negative infections.

Ninety patients (41 males, 49 females) with a diagnosis of meningitis, urinary tract infection (UTI), gastroenteritis or other miscellaneous gram-negative infections were enrolled. Their ages ranged from 7 days to 10 years, with a mean age of 4 months. 58 (63%) patients had an etiology confirmed by either positive culture (52; 89%) or latex agglutination (6; 10%). 41 of these patients had meningitis diagnosed by positive CSE culture (38) or by positive CSF latex agglutination (3); 27/41 patients also had positive blood cultures. Aztreonam MIC100 for 27 isolates of Haemophilus influenzae, all ampicillin-sensitive, was 0.19 micrograms/ml; 4 Salmonella sp., 1 Neisseria meningitidis and 1 Serratia marcescens isolates were inhibited by 0.19 micrograms/ml, and the MIC100 for 2 Klebsiella pneumoniae, 1 Proteus vulgaris and 2 Pseudomonas aeruginosa isolates were 0.045 and 0.19, 0.022 and 12.5 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulbactam/ampicillin vs. chloramphenicol/ampicillin for the treatment of meningitis in infants and children.

Eighty-one patients ages one month to 14 years with meningitis were randomized to receive either sulbactam (50 mg/kg per day) and ampicillin (400 mg/kg per day; 41 patients) or chloramphenicol and ampicillin (40 patients). The groups were comparable in terms of sex and degree of illness; however, more patients treated with chloramphenicol/ampicillin than patients treated with sulbactam/ampicillin were younger than 12 months of age (78% vs. 56%). Pathogens were isolated from the cerebrospinal fluid (CSF) of 65 (80%) of the 81 patients. In the sulbactam/ampicillin group, there were 18 Haemophilus influenzae isolates (one resistant to ampicillin), five Streptococcus pneumoniae, five Neisseria meningitidis, one Klebsiella pneumoniae, one Pseudomonas aeruginosa, and one Listeria. In the chloramphenicol/ampicillin group, there were 19 H. influenzae isolates, 10 S. pneumoniae, three N. meningitidis, one Haemophilus parainfluenzae, and one Citrobacter. Of 63 patients with assessable CSF pathogens, one (3%) of 29 treated with sulbactam/ampicillin died (S. pneumoniae) and six (18%) of 34 treated with chloramphenicol/ampicillin died (two, H. influenzae; three, S. pneumoniae; and one, Citrobacter). Twelve percent in the sulbactam/ampicillin group and 18% in the chloramphenicol/ampicillin group had neurologic sequelae. No clinically significant reactions or toxicities were noted. Sulbactam/ampicillin was as effective as chloramphenicol/ampicillin in the treatment of meningitis.

Ceftazidime vs. standard therapy for pediatric meningitis: therapeutic, pharmacologic and epidemiologic observations.

One hundred patients ages 1 month to 15 years received either ceftazidime (CZ) at a dose of 150 mg/kg/day divided every 8 hours or conventional treatment with chloramphenicol and ampicillin (CA). Seventy-eight had isolates recovered from the cerebrospinal fluid: 40 (51%) were Haemophilus influenzae (all ampicillin-susceptible); 16 (21%) were Streptococcus pneumoniae; 14 (18%) were Neisseria meningitidis; 3 (4%) were salmonellae; 1 (2%) was Pseudomonas; and 1 (2%) was Group B Streptococcus. Six patients with negative cerebrospinal fluid culture had positive latex agglutination (two H. influenzae, three N. meningitidis, one S. pneumoniae). Sixty-one patients had positive blood cultures. CZ inhibited 100% of H. influenzae at 0.78 micrograms/ml, S. pneumoniae at 0.39, N. meningitidis at 0.04 and salmonellae at 0.39 micrograms/ml. The mean peak serum concentration of CZ was 36.4 micrograms/ml with a mean cerebrospinal fluid level of 7.4 micrograms/ml. If one eliminates from the statistics those patients who died less than or equal to 24 hours after admission, five (10%) of 49 patients treated with CZ died, one (2%) improved and 43 (88%) were cured. Overall 29 patients died, 12 receiving CZ (20%) and 8 receiving CA (21%). There were no significant CZ-related toxicities. Gross neurologic sequelae were noted in 5% of 38 CZ patients and 4% of 28 CA patients. CZ compared favorably to CA for treatment of meningitis.

Ceftazidime in the treatment of meningitis in infants and children over one month of age.

Ceftazidime, a new beta-lactamase-resistant cephalosporin, was compared with a combination of ampicillin and chloramphenicol for the treatment of meningitis in 100 infants and children aged one month to 15 years. In this open, randomized trial conducted in the Dominican Republic, 61 patients received 50 mg/kg of ceftazidime intravenously every eight hours; 39 received ampicillin plus chloramphenicol in conventional dosages. Seventy-eight of the patients had discernible isolates in samples from cerebrospinal fluid, six had a positive diagnostic Directogen result, and the remainder either had miscellaneous pathogens evident in samples of cerebrospinal fluid, bacteriologic growth in cultures of blood samples only, or no bacteriologic growth in cultures of either cerebrospinal fluid or blood. Among patients with discernible etiologic agents in samples of cerebrospinal fluid, 11 of 57 (19 percent) ceftazidime-treated patients died, and five of 27 (19 percent) patients treated with the combination died. Mortality by pathogen was as follows for patients who received ceftazidime or ampicillin plus chloramphenicol, respectively: Hemophilus influenzae, two of 27 (7 percent) and one of 15 (6 percent); Streptococcus pneumoniae, six of 12 (50 percent) and two of five (40 percent); Neisseria meningitidis, none of 11 (0 percent) and one of six (17 percent); and Salmonella, neither of two (0 percent) and one of one (100 percent). Overall mortality in the ceftazidime group was 20 percent versus 21 percent in the combination group. No significant toxicities were noted in the patients treated with ceftazidime.