Incidence of invasive Haemophilus influenzae type b infections in Filipino children.
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Biomedical subjects
Publications and source records attributed to H Nohynek.
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Finland has, until recently, had a very low incidence of hepatitis B infection, reflected in transmission mainly amongst adolescent and adult age-groups with high-risk behaviour. Several recent local outbreaks of acute hepatitis B in Finland may indicate a change in the epidemiology of this infection. We examine time trends of hepatitis B notifications to the new national infectious disease registry. We also analyse all hepatitis B cases notified over the 2-y period from 1 January 1995 to 31 December 1997 by age, sex, place of residence, country of birth and reported route of transmission. The reported incidence of acute hepatitis B increased 3-fold over this period. The main reported route of transmission was related to injecting drug use, although a significant proportion of adolescent female cases was reportedly infected through heterosexual intercourse. A critical evaluation of the current targeted vaccination approach and other prevention policies is required.
In searching for suitable methods for aetiological diagnosis of pneumococcal disease we determined capsular polysaccharide, C-polysaccharide and pneumolysin antibodies bound in immune complexes (IC) in Filipino children. Sera were obtained from 150 healthy infants (all under 12 months old) and from 350 paediatric patients (mean age 18 months) hospitalized with severe pneumonia. The findings in healthy children were not associated with age, sex or pneumococcal carrier status; 3-7% exceeded the cut-off limits for positivity in different antibody assays. By contrast, 97 (51%) of the 190 patients with a complete 3-sample series exceeded the cut-off limit for IC-bound pneumolysin-IgG in at least 1 of the serum samples studied. Positivity rates for IC-bound pneumolysin-IgG in the admission day, in-patient and convalescent sample of the 350 patients were 25%, 25% and 34%. Pneumolysin-IgM, capsular polysaccharide and C-polysaccharide antibodies in the IC were positive in only 4-6% of the patients' samples. IC-bound pneumolysin-IgG antibody assay seem to be a useful method for species-specific diagnosis of pneumococcal infections.
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BACKGROUND: Pregnant women in developing countries are vaccinated with tetanus toxoid (TT) to prevent neonatal tetanus. In populations in which the maternal TT-vaccination program is efficiently implemented, responses of the infant to TT and TT-conjugated vaccines such as Haemophilus influenzae type b (Hib) capsular polysaccaride (PS) TT-conjugate (Hib-TT) vaccine may be depressed. OBJECTIVES: To study the influence of transplacentally acquired anti-TT antibodies on responses to TT vaccination and to Hib-TT vaccine. METHODS: One hundred ninety-four healthy Filipino infants received three doses of a Hib conjugate (either Hib-TT, PRP-OMP or HbOC) with diphtheria-tetanus-pertussis vaccine (DTP) given simultaneously but in a separate syringe at the age of 6, 10 and 14 weeks (primary series). In addition 54 of the study children received a booster dose of Hib-TT at 9 months simultaneously with the measles vaccine. RESULTS: Transplacentally acquired anti-TT did not interfere with the anti-Hib PS antibody (anti-Hib PS) response to any of the conjugates. The transplacentally acquired anti-TT was not significantly associated with the concentration of anti-Hib PS either before or after the booster dose of Hib-TT. High concentrations (> or =1 IU/ml) of transplacentally acquired anti-TT inhibited the infants' anti-TT responses. CONCLUSIONS: High concentration of transplacentally acquired anti-TT did not depress anti-Hib PS responses to the Hib-TT vaccine. On the other hand the high anti-TT concentrations somewhat depressed the anti-TT responses of the infants. However, the anti-TT concentrations attained were in the protective range in all study children after either the primary series (DTP + Hib-TT) or the booster dose of Hib-TT.
This paper describes 2 outbreaks of hepatitis A infection in Finland, a very low endemic area of hepatitis A infection, where a large proportion of the population is now susceptible to infection by hepatitis A virus (HAV). The first outbreak involved people attending several schools and day-care centres; the second employees of several bank branches in a different city. The initial investigation revealed that both were related to food distributed widely from separate central kitchens. Two separate case-control studies implicated imported salad food items as the most likely vehicle of infection. HAV was detected in the stool of cases from both outbreaks using reverse-transcriptase polymerase chain reaction; however, comparison of viral genome sequences proved that the viruses were of different origin and hence the outbreaks, although occurring simultaneously, were not linked. Foodborne outbreaks of HAV may represent an increasing problem in populations not immune to HAV.
Serum antibody responses to three Haemophilus influenzae type b (Hib) capsular polysaccharide-protein conjugate vaccine (PRP-OMP, PRP-T, and HbOC) were evaluated in 174 Philippine infants after a primary vaccination series. Children were randomized to receive one of the Hib vaccines (Hib groups) or into a control group. Vaccination was carried out at six, 10 and 14 weeks of age based on the local Expanded Program of Immunization schedule. Sera were collected at six weeks of age for the Hib groups and one month after the third dose for all subjects. Anti-Hib concentrations were determined by the Farr-type radioimmunoassay. There were no significant differences (P = 0.3626) in the prevaccination anti-Hib geometric mean concentration (GMC) among the three Hib groups. Differences in the GMC after the primary series of three doses were significant (P < 0.0001); GMC was highest for PRP-T (6.62 micrograms/ml), followed by HbOC (1.9 micrograms/ml), then PRP-OMP (1.06 micrograms/ml), and lowest for the control group (0.11 microgram/ml). We conclude that all three Hib conjugate vaccines (PRP-T, HbOC, and PRP-OMP) were immunogenic after three primary doses among Philippine infants.
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Bacterial antibodies were studied in acute, intermediate and convalescent phase sera (mean duration from first to last sample 36 days) of 121 children hospitalized for acute lower respiratory tract infection. Antibody responses were observed in 45% of all cases and in 29% of the 21 children < 1 year old. A total of 15 responses to Streptococcus pneumoniae (pneumolysin), 20 to Haemophilus influenzae, 9 to Moraxella catarrhalis, 3 to chlamydiae and 8 to Mycoplasma pneumoniae were found. In 79 patients with 4 consecutive samples available, 52% of the 31 responses were measurable within 5 days from admission. Overall the responses were not associated with upper respiratory tract bacterial findings or acute otitis media. Significantly more responses were found in the 121 children with acute lower respiratory tract infection than in healthy controls (P < 0.007). We conclude that bacterial antibody assays provide a useful tool in the study of the etiology of acute lower respiratory tract infection in young children, even if the interval between paired serum samples is short.
The clinical signs, symptoms and host responses (erythrocyte sedimentation rate, white blood cell count and C-reactive protein) were studied to distinguish bacterial from viral acute lower respiratory infection (ALRI) in 121 children hospitalized for ALRI. Etiologic diagnosis was based on blood culture, antibody assays and antigen detection. Children with bacterial involvement only were older than those with viral involvement alone (mean, 5.1 vs. 2.5 years), and their duration of respiratory symptoms had lasted longer (mean, 4.6 vs. 3.3 days). Children with unknown etiology had a shorter duration of fever before hospitalization than those with etiology identified with the methods used (mean, 1.6 vs. 2.9 days). The host response ranged widely within etiologic groups. The mean erythrocyte sedimentation rate did not differ significantly between the bacterial and viral ALRI (38 vs. 28 mm/hour); neither did white blood cell count (13.2 vs. 13.6 x 10(9)/liter) or C-reactive protein (68 vs. 49 mg/liter). No combination of clinical signs and host responses or any cutoff values could be shown to differentiate reliably bacterial from viral ALRI.
Two sampling techniques, nasal swabbing and oropharyngeal swabbing, for detection of the upper respiratory tract carriage of Streptococcus pneumoniae and Haemophilus influenzae were studied prospectively with 296 healthy Filipino infants at various ages: 6 to 8, 10 to 12, 14 to 17, 18 to 22, 32 to 39, and 46 to 65 weeks. In all age groups S. pneumoniae was isolated significantly more often (P < 0.0001) from the nasal site than from the oropharyngeal site. H. influenzae was found equally often at both sites.
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A prospective eight-month study was carried out in 50 children admitted to hospital for radiologically confirmed community-acquired pneumonia. A potential causative agent of infection was identified in 44 (88%) cases. Using virus isolation, virus antigen detection and enzyme immunoassay serology, respiratory virus infection was diagnosed in 30 (60%) patients. Antibody assays for seven bacteria and antigen detection from serum and urine for Streptococcus pneumoniae produced evidence of bacterial infection in 31 (62%) cases. Streptococcus pneumoniae (38%), respiratory syncytial virus (30%) and Mycoplasma pneumoniae (20%) were the most common causative agents. A mixed infection was diagnosed in 25 (50%) episodes. Nine patients failed to respond to antibiotics within 24 h after onset of treatment. Three of them had a pure viral infection, three a mixed viral-bacterial infection, two a Mycoplasma pneumoniae infection mixed with other bacteria and one a pure Mycoplasma pneumoniae infection. All three Mycoplasma pneumoniae infections were initially treated with penicillin.
OBJECTIVE: To determine the etiologic agents in children with acute lower respiratory infection. DESIGN: A survey of a series of patients. SETTING: General pediatric hospital serving an urban population with and without referrals in Helsinki, Finland. PARTICIPANTS: 135 Finnish children aged 2 months to 15 years (mean, 1.75 years), with clinically defined acute lower respiratory infection (with difficulty of breathing), or found to have fever and a pneumonic infiltrate on chest roentgenogram. SELECTION PROCEDURES: Consecutive sample on voluntary basis. INTERVENTIONS: None. MAIN RESULTS: Of 121 children with adequate samples, an etiologic diagnosis could be established in 84 (70%): 30 (25%) had bacterial, 30 (25%) viral, and 24 (20%) mixed infections. Antibody assays alone identified the agent in 91% of positive cases. CONCLUSIONS: Bacterial infections are common but generally underestimated in acute lower respiratory infection; serologic methods add significantly to their detection.
Tumor necrosis factor-alpha (TNF alpha) concentrations were measured by radioimmunoassay in sera of 118 children (median age, 1.7 years; range, 2 months-15 years) hospitalized for acute lower respiratory tract infection (ALRI). Both viral and bacterial ALRI were associated with elevated concentrations of TNF alpha. Concentrations greater than 40 ng/l were seen in children with bacterial or mixed ALRI in 64% and with viral ALRI in 50% of cases. Elevated concentrations were associated with longer duration of fever before admission (P less than .05) and with a higher serum C-reactive protein concentration (P less than .05). There were no significant differences in TNF alpha concentrations between gram-positive and gram-negative infections, nor was there an association with clinical severity of ALRI. TNF alpha concentrations decreased in most patients to normal within 5 days of hospitalization, irrespective of the etiology of the infection.
A modified tube agglutination test using type-specific latex reagents for detection of pneumococcal capsular polysaccharide antigens in alkalinized, unconcentrated urine samples was evaluated in reconstituted urine samples and in groups consisting of 26 children with clinical and roentgenographic evidence of acute lower respiratory tract infection, six patients with blood culture-proven infection of nonpneumococcal etiology, and 30 healthy individuals. The sensitivity of the tube latex agglutination method for pneumococcal polysaccharides was 2 to 10 times higher than that of the slide agglutination method. Positive antigen findings were obtained for 42% of urine samples from patients with acute lower respiratory tract infection but in neither patients with nonpneumococcal septicemia nor healthy controls. Fifty-five percent of the antigen-positive patients also showed evidence of pneumococcal involvement by pneumococcal antibody assay or antigen detection in acute-phase serum.
Differences in the magnitude of antibody response after one, two or three doses of Haemophilus influenzae type b conjugate vaccines have been reported which may influence decision-making regarding which vaccine should be used. This is of particular importance in developing countries where children may not receive a full immunization series and the vaccination schedule may be delayed. Serum antibody responses to three Hib capsular polysaccharide protein conjugate vaccines (PRP-OMP, HbOC and PRP-T) were evaluated in 102 Filipino infants. Vaccination was carried out at 6, 10 and 14 weeks of age based on the national Expanded Programme on Immunization (EPI) schedule together with diphtheria-tetanus-pertussis, hepatitis B and oral poliomyelitis vaccines. Sera were collected at 6 weeks and 1 month after each vaccination. Anti-Hib polysaccharide antibody concentrations were determined by Farrtype radioimmunoassay (RIA) and enzymeimmunoassay (EIA), Following the first dose, the geometric mean concentrations (GMC, micrograms ml-1) for PRP-OMP, HbOC and PRP-T were 0.69, 0.27 and 0.38, respectively. After two doses, there was a significant response (P < 0.05) to PRP-OMP and PRP-T (0.89 and 1.47) but not for HbOC (0.37). Differences in the GMC after the primary series were significant (pairwise P < 0.05): GMC was highest for PRP-T (4.0), followed by HbOC (1.6) and PRP-OMP (1.1). All three Hib vaccines were immunogenic when given in the local EPI schedule in Filipino infants although significant differences in the kinetics and magnitude of antibody responses were noted. The anti-Hib antibody concentrations determined by RIA and EIA were also compared in order to validate the latter for use in laboratories where it is feasible. There was a good correlation (r2 = 76%; P = 0.0001) in the Hib antibody titres obtained by both assays.