H influenzae in the post-vaccination era.
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Biomedical subjects
Publications and source records attributed to H Peltola.
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Clinical efficacy of norfloxacin for treatment of traveler's diarrhea in 106 Finnish tourists vacationing in Morocco was evaluated during two different seasons. When the criteria for diagnosis of traveler's diarrhea were fulfilled, norfloxacin (400 mg) or a placebo was given orally, twice daily for 3 days. All symptoms and signs subsided sooner in the norfloxacin group. The clearest difference was observed in the duration of diarrhea: 1.2 days in the norfloxacin group vs. 3.3 days in the placebo group (P < .001). The duration of diarrhea due to particular species was as follows for the two groups: in cases due to Salmonella enterica, 1.1 vs 4.1 days (P < .01); in cases due to Campylobacter jejuni, 1.8 vs. 5.0 days (P < .01); and in cases due to enterotoxigenic Escherichia coli, 1.0 day vs. 3.1 days (P < .01). The rate of full recovery during administration of norfloxacin or a placebo was also greater among the norfloxacin recipients: 84% vs. 47% (P < .001). No significant adverse effects were reported. Norfloxacin proved to be safe and effective in therapy for traveler's diarrhea.
The relationship between length of prediagnostic history and course and sequelae of childhood bacterial meningitis was prospectively examined by collecting data from 286 children with bacteriologically confirmed bacterial meningitis. The cases were divided into three groups: short (< or = 24 hours, N = 141); intermediate (> 24 to 48 hours, N = 75); and long (> 48 hours, N = 70) history. The level of consciousness and serum C-reactive protein normalized sooner during hospitalization in patients with a longer history. They also showed neck stiffness more often and longer and had thrombocytosis earlier and more prominently than patients with a shorter history. The differences were not influenced by etiology, sex or age. The occurrence of neurologic abnormalities in the hospital or during the first 6 months after discharge was not affected by duration of illness before hospitalization. We conclude that our results support the view that bacterial meningitis presents in two forms. At presentation the more acute form often has a history of less than 24 hours and poses a great danger to the patient. In contrast the other form develops insidiously and is more difficult to detect but does not have a worse prognosis than the acute form.
An acute thrombocytopenic purpura developed shortly after measles-mumps-rubella vaccination in 23 of approximately 700,000 children immunized over a period of seven years. The mean interval from inoculation to the onset of purpura was 19 days. Bone marrow aspirates obtained from 13 patients showed increased or normal amounts of megakaryocytes. Platelet survival time was markedly shortened in the two patients studied. Fifteen patients recovered (the platelet count exceeded 100 x 10(9)/l) in one month, five in two months and two in six months. Increase in platelet-associated immunoglobulin was detected in 10 of 15 patients. Circulating antiplatelet autoantibodies (AAb) against glycoprotein IIb/IIIa were detected in 5 of 15 patients. The findings are compatible with an autoimmune mechanism triggered by immune response to measles-mumps-rubella vaccination. As evaluated by the clinical course and the presence of AAb, post-vaccination thrombocytopenic purpura appears to be indistinguishable from childhood acute idiopathic thrombocytopenic purpura.
The purpose of the study was to evaluate the history, clinical picture and diagnostic difficulties of acute haematogenous osteomyelitis (AHOM) in children. Forty-seven children under the age of 15 with bacteriologically proven AHOM were collected prospectively in Finland in 1981-93. Staphylococcus aureus was responsible for 89% of the cases. The commonest sites affected were the tibia (25%) and the femur (23%) followed by the pelvis (15%) and the calcaneus (11%). Sites other than the long bones increased in frequency in children over the age of 4 years. Most of the children came with a history of a week or less with classic signs and symptoms of AHOM, increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values but negative X-rays. Delay in hospital admission was observed in 19%. In 11% antimicrobial therapy was not instituted within 48 hours on ward. All children were clinically healthy at the 1-year check-up with minor X-ray changes seen in 11 patients. We conclude that children in Finland seek treatment early in the course of AHOM and have a good outcome. S. aureus is the main aetiological agent affecting primarily the long bones, but in older children pelvic and calcaneic sites are also frequent. No significant delays affecting the outcome were noticed in admittance to hospital or in the diagnosis of AHOM.
Mortality from meningitis caused by Haemophilus influenzae type b (Hib), a disease that affects mainly infants and young children, can reach 5% in industrialised countries and ten times that in non-industrialised countries. To determine the efficacy of vaccination against Hib, we carried out a retrospective survey of the incidence of Hib meningitis over five decades in the Greater Helsinki area of Finland, where all children with bacterial meningitis are treated in one of three centres. Except for a meningococcal epidemic in the early 1970s, Hib was the leading cause of childhood bacterial meningitis until the Hib conjugate vaccines changed the picture profoundly. In 1986-87 the polysaccharide-diphtheria toxoid conjugate (PRP-D) was given experimentally to 50% of infants. In 1988-89 all infants were vaccinated, 50% with PRP-D, 50% with another conjugate vaccine, the oligosaccharide-CRM197 protein conjugate (HbOC). Since 1990 a third conjugate vaccine, the polysaccharide-tetanus toxoid (PRP-T), has been administered routinely to all infants. The vaccines were administered at age 3-6 months, with a booster dose at 14-18 months. In the first 5 years of the Hib vaccination programme the number of cases of Hib meningitis in children aged 0-4 years fell sharply, from 30 in 1986 (the first year of the programme) to none in 1991. The decline contrasts sharply with the rising trend up to the mid 1980s. Vaccination seems to be the only explanation for the observed change in the epidemiology of Hib meningitis.
The first Finnish trial with Haemophilus influenzae type b vaccine was conducted during 1973-1974. It demonstrated that the polysaccharide vaccine was 90% efficacious in children greater than or equal to 18-24 months old. The immunologically superior polysaccharide-protein conjugate vaccines have been used since 1986 in randomized trials. The PRP-D vaccine (polysaccharide conjugated to diphtheria toxoid) was 90% efficacious when given at 3, 4, and 6 months of age to 58,000 infants. In 1988-1989, the PRP-D vaccine was compared with the HbOC vaccine (oligosaccharide conjugated to CRM197 protein). Follow-up is continuing, but both vaccines seem to be efficacious after two doses in infancy.
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The etiology of travelers' diarrhea was studied in 579 adult Finnish tourists participating in two packaged tours to Morocco in the winter (n = 233) and fall (n = 346) of 1989. A research team accompanied the travelers, and a laboratory for enteric pathogens was established in Agadir. At least one pathogen was found in 62% of the 60 diarrhea cases in winter and in 58% of the 111 diarrhea cases in fall. Multiple pathogens were found less often in winter (8%) than in fall (21%, P less than .05). Campylobacter strains were the leading cause of travelers' diarrhea in winter, found alone or with other pathogens in 28% of the cases (but in only 7% in fall), whereas enterotoxigenic Escherichia coli (ETEC) was the most common pathogen in fall, present in 32% of the cases (8% in winter). Both differences are highly significant (P less than .001). Salmonella enterica was almost as common as ETEC in fall (25% of diarrhea cases) but rare in winter (10%, P less than .05). Thus, the etiology of travelers' diarrhea varied according to the season in the same tourist destination. This finding has relevance to both antimicrobial treatment and prophylaxis.
Invasive disease caused by Haemophilus influenzae type b (Hib) is typically a disease of young children, starting when the protection afforded by maternal antibodies is exhausted and ending when the child's own antibody production to the Hib capsular polysaccharide begins efficiently. There are, however, large variations between population groups in the incidence of the disease and the age at which it appears. Potential factors behind this variation include virulence genes of the bacteria and genetic susceptibility genes of the host. Although such genes and their effects can be identified, their impact on the disease's incidence is only minor. Potentially much more important appear to be socioeconomic factors that to a large extent determine the exposure of the child to Hib and to other infectious agents that may enhance both colonization and invasive infection by Hib.
Seventy-two children with early measles (1st-3rd day of rash), presenting at two centres in Santiago, Chile, were classified as having mild ('ordinary measles', n = 50), or moderate to severe measles ('primarily severe measles', n = 22). The level of serum C-reactive protein (CRP) was determined by nephelometry from a finger prick sample. The mean CRP value in ordinary measles, 19 mg/l, was significantly lower (P less than 0.001) than in primarily severe measles where the mean CRP was 65 mg/l. During late measles (5th-8th day of rash), the mean CRP was 19 mg/l if the child recovered uneventfully (n = 35), whereas the mean level of 123 mg/l (P less than 0.001) was encountered when the child suffered from complicating pneumonia (n = 22). We conclude that the simple quantitative CRP determination is a useful alarm signal during the course of measles: elevated levels point to severity or complications in recovery.
To assess factors affecting the development of reactive thrombocytosis during bacterial meningitis, thrombocyte counts of 311 children with cerebrospinal fluid culture-positive bacterial meningitis were followed during hospitalization. Thrombocytosis (platelet counts greater than 500 x 10(9)/liter) was seen in 49% of the patients after the first week of treatment. Thrombocyte counts were higher in infants and in patients with long duration of illness before admission. Subdural effusion and cephalosporin therapy were associated with more pronounced thrombocytosis We found no relation between thrombocytosis and neurologic complications, but the patients who died developed thrombocytopenia instead of thrombocytosis. The difference between the thrombocyte curves of the surviving and dying patients might be utilized in predicting the final outcome in the severest cases of bacterial meningitis. We speculate that inflammatory cytokines, especially interleukin 1-beta, induce reactive thrombocytosis in bacterial meningitis.
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The pharmacokinetics of orally administered ciprofloxacin (CIP) was studied in seven infants aged 5 to 14 weeks and nine children aged 1 to 5 years, most of whom were Salmonella carriers. In each case, 15 mg of CIP per kg of body weight was given with water on an empty stomach, and timed serum samples were taken during the following 12 h. The elimination half-life of CIP was significantly (P less than 0.001) longer in the infants (2.73 +/- 0.28 h; mean +/- standard deviation) than it was in the children (1.28 +/- 0.52 h). The area under the serum CIP concentration-time curve (AUC) from time zero to infinity was 16.1 +/- 7.4 mg.h.liter-1 among the infants and 5.3 +/- 3.3 mg.h.liter-1 in the children (P less than 0.01). No significant differences in the maximum concentration in serum, time to maximum concentration in serum, or absorption half-life were observed between the two groups. In contrast, the mean residence time was twofold longer in the infants (4.6 h) than it was in the children (2.4 h; P less than 0.001). The findings suggest that elimination of CIP is particularly rapid in children who just have passed infancy; they may require doses at shorter time intervals than those required by infants or older children or adults. In general, an oral dose of 10 to 15 mg of CIP per kg three times daily seems appropriate for children aged 1 to 5 years.
Precise quantity of fever was determined in 191 cases of childhood bacterial meningitis by calculating the areas between the line indicating 37.8 degrees C or 39.5 degrees C temperature and the line connecting all individual temperature values. Temperature measurements were performed rectally one to four times a day throughout the hospitalization. The obtained areas under the curves (AUC), expressed as degree-hours, proved to be a sensitive index for delineating each individual fever pattern and reflected the magnitude of fever more precisely than the traditional fever curves. Children under five had significantly (p less than 0.05) greater AUC than those at five to 15 years; similarly, patients with Haemophilus influenzae meningitis showed greater AUC (i.e., had more fever) than those with meningococcal disease (p less than 0.05). The overall rates of secondary (14%), persistent (16%), and prolonged fever (8%) were virtually identical to previous reports; no drug fever was reported in this study. In cases with prolonged fever, a significantly higher rate (40%) of neurological complications was found compared to those who became afebrile earlier. This method is potentially utilizable in other diseases and conditions where precise measurement of fever is of clinical or scientific relevance.
Twenty-five patients with clinical exanthema subitum (roseola infantum) were enrolled into a study, where acute-phase and convalescent sera were examined for antibodies to human herpesvirus 6 (HHV-6), several other viruses, and other microbes. In addition, an acute-phase fecal specimen was examined for viruses by electron microscopy. Confirmative or suggestive serologic evidence for recent HHV-6 infection was obtained in 23 (92%) cases. Conversion to HHV-6 was found in 19 (76%), a diagnostic (greater than or equal to 4-fold) titer rise in 2, a twofold titer rise in 1, and a stable relatively high titer in 1 of the patients; only 2 (8%) individuals remained negative. The other microbial assays produced only two slight mycoplasma antibody rises and one rotavirus identification in the fecal specimen. It is concluded that if the clinical diagnosis of exanthema subitum is deemed doubtful, HHV-6 infection is verifiable in about 75% of the cases by serology.
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