Secondary Haemophilus influenzae type b in day-care facilities. Risk factors and prevention

The risk factors for acquisition of secondary day-care-associated Haemophilus influenzae type b disease were evaluated in a cohort of children in Seattle-King County, Washington; Atlanta; and the state of Oklahoma. During the study period, 129 primary cases were identified in children less than 5 years old who attended day-care facilities. In ten instances (8%), a secondary case occurred between one and 60 days after a primary case in the same classroom. Risk of secondary disease in classroom contacts was strongly age related: 2.4% in children 0 to 11 months old, 1.2% in children 12 to 23 months old, and 0.0% in children 24 to 59 months old. Controlling for age, children attending day-care more hours per week were more likely to transmit or acquire secondary disease. Risk of secondary disease for children in other classrooms at a center where a case had occurred was not significantly greater than risk of primary disease. Administration of rifampin to classroom contacts of a child with invasive H influenzae was effective in preventing secondary cases (95% confidence interval for rifampin efficacy, 47% to 100%). For children 0 to 23 months old not treated with rifampin, risk of secondary disease was 2.7% (95% confidence interval, 1.1% to 4.3%), a risk approaching that reported in household contacts.     

Rifampin alone or with trimethoprim for contacts of children with Haemophilus influenzae type b infections.

We carried out a nonrandomized, unblinded study to compare the efficacy of rifampin alone with that of rifampin in combination with trimethoprim in the eradication of the Haemophilus influenzae type b (HIB) carrier state among contacts of patients with invasive HIB infection. The study population comprised 17 index patients admitted to hospital with severe HIB infections and 233 contacts, 43 of whom had nasopharyngeal colonization with HIB of the same biotype as that of the index patient. Rifampin in a daily dose of 20 mg/kg (maximum 600 mg) for 4 days eradicated the carrier state in 86% of cases, as did the combination of rifampin at the same dosage and trimethoprim in a daily dose of 5 mg/kg (maximum 160 mg) for 4 days.     

Hemophilus influenzae type b disease. An epidemiologic study with special reference to day-care centers

Day-care centers are a relatively new phenomena of American society that bring together large numbers of young children susceptible to contagious disease. This study examines the incidence and risk factors of endemic Hemophilus influenzae type b disease both in the general population and in day-care attendees in Monroe County, New York, for 1982 and 1983. The attack rate in the general population (excluding day-care attendees) was highest in children younger than 1 year (131.9 cases per 100,000 per year) and in those 1 to 2 years old (75.7 cases per 100,000 per year) compared with older children. The relative risk for day-care attendees was much greater than that of the general population. It was 12.3 times greater for children younger than 1 year, 7.2 times greater for those 1 to 2 years old, and 3.8 times greater for those 2 to 3 years old. We conclude that children attending day-care facilities face a substantial increased risk of contracting invasive H influenzae type b disease. Efforts to prevent susceptibility and contagious spread of this disease in this population seem necessary.     

Haemophilus influenzae type b disease. Incidence in a day-care center.

Haemophilus influenzae type b (HIB) disease was observed during a 14-month period in seven of 48 infants attending a day-care center. Surveillance studies showed that 28 (58%) infants had positive nasopharyngeal cultures for HIB; four infants were colonized with HIB for nine to 12 months. Ampicillin trihydrate prophylaxis failed to reduce the HIB carrier rate. Haemophilus influenzae type b polysaccharide vaccine was administered to 34 of the children. Sera obtained prior to immunization showed detectable antibody in all infants. Only nine (26%) infants had twofold or greater rises in serum HIB antibody titers after vaccination. Antibody response was independent of age, preimmunization antibody concentration, and HIB carrier status. In one infant, HIB meningitis developed four months after she received polysaccharide vaccine. This outbreak emphasizes that HIB is highly contagious in closed populations of young, susceptible infants.     

Invasive Haemophilus influenzae infections in men with HIV infection.

OBJECTIVE--To determine the incidence of invasive Haemophilus influenzae disease in men with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection and the proportion of disease due to serotype b. DESIGN--Population-based, active surveillance. SETTING--San Francisco (Calif) Department of Health. PARTICIPANTS--All men 20 to 49 years of age with invasive H influenzae disease. RESULTS--The cumulative incidences of invasive H influenzae disease in men 20 to 49 years of age with AIDS and in HIV-infected men 20 to 49 years of age without AIDS were 79.2 and 14.6 per 100,000, respectively, but only 33% of cases were due to serotype b. The corresponding rates for invasive H influenzae b disease were 11.3 and 7.6 per 100,000. CONCLUSIONS--Men with AIDS or HIV infection are at increased risk of invasive H influenzae infections, including H influenzae b, but such infections are still infrequent in this population.     

Cluster of Haemophilus influenzae type b infections in adults

Haemophilus influenzae type b commonly causes illness in young children, among whom transmission is known to occur. Most adults are believed to be immune to H influenzae type b and outbreaks of disease among adults appear to be uncommon. From July 14 to Aug 12, 1985, a cluster of six cases of acute febrile illness with cultures positive for H influenzae, biotype II (five cases) or untyped H influenzae (one case), occurred among adults in a nursing home and an adjoining hospital. All six case-patients had personal contact with at least one other case-patient. Among the 46 nursing home residents, men were more likely than women to become ill (44% vs 0%). This cluster of disease suggests that elderly adults may be more susceptible to H influenzae infection than is generally recognized and that outbreaks among adults may result from person-to-person transmission.     

Rapid detection of Haemophilus influenzae and Haemophilus parainfluenzae in nasopharyngeal swabs by multiplex PCR

Objective To establish multiplex PCR-based assays for detecting H.influenzae and H.parainfluenzae.And the PCR-based assays were applied to detect the carriage rates of H.influenzae and H.parainfluenzae in nasopharyngeal swab specimens which were collected from healthy children.Methods Multiplex primers for species-specific PCR were designed by using DNAstar soft based on the sequences of 16S rRNA genes from genus Haemophilus to detect H.influenzae and H.parain fluenzae.Results The sensitivity of the 16S rRNA PCR assay for detecting H.influenzae and H.parainfluenzae was 97.53％ and 100％ respectively,and the specificity was 95.89％ and 96.63％ respectively.Youden's Index on the ability to detect H.influenzae and H.parainfluenzae was 0.9342 and 0.9663 respectively.666 nasopharyngeal swab specimens were collected from healthy children.The detection rates of H.influenzae and H.parainfluenzae were 14.11％ and 16.07％ respectively by using isolation and culture methods.The detection rates of H.influenzae and H.parainfluenzae were 43.54％ and 57.96％ respectively by 16S rRNA PCR assays.The carriage rates of serotypes a,b,c,d,e,f and non-typeable isolates were 0％ (0/666),0.15％ (1/666),1.20％ (8/666),0.15％ (1/666),1.20％ (8/666),1.80％ (12/666),95.50％ (636/666) respectively.Conclusion The multiplex PCR assays were very rapid,reliable and feasible methods for detection of H.influenzae and H.parainfluenzae in pharyngeal swab specimens which were compared to conventional isolation and culture methods.95.5％ of H.influenzae strains in healthy children were nontypeable.The encapsulated or typable strains were mainly three serotypes which was c,e,and f serotype.     

Invasive Haemophilus influenzae infection in the Australian Capital Territory region.

OBJECTIVE: To investigate the pattern of invasive Haemophilus influenzae disease in the Australian Capital Territory (ACT) region with a view to assessing the possible benefits of vaccination in this community. SETTING AND DESIGN: The microbiology department of Royal Canberra Hospital processes all specimens from the three public hospitals in the ACT. Together these hospitals provide all paediatric medical and approximately 80% of adult inpatient beds available in the ACT. We identified all laboratory isolates of H. influenzae obtained from normally sterile sites from 1984 to 1990, and reviewed the clinical records of these patients. Also included in this analysis were all cases of acute epiglottitis identified in hospital discharge summaries, intensive care and coroners' records. Epidemiological, clinical and microbiological data were gathered and assessed. RESULTS: We identified 138 cases of infection. Forty per cent (36 of 66 cases of meningitis, 5 of 44 cases of epiglottitis, 10 of 12 cases of cellulitis) occurred in children aged less than 18 months. Meningitis (48%), epiglottitis (32%), cellulitis (9%) and primary bacteraemia (4%) were the most common syndromes seen. The annual incidence of invasive H. influenzae disease in Canberra was 63.2 per 100,000 children aged under five years. Approximately 1 in 225 children under five years of age and resident in Canberra developed invasive H. influenzae disease. Ninety-eight per cent of isolates serotyped were type b. CONCLUSION: A vaccination program effective in preventing H. influenzae type b infection, completed in infants before 6 months of age, could prevent upwards of 80% of invasive H. influenzae disease in our population. Such a program should be cost effective although precise assessment is hampered by the lack of accurate data on the acceptance rate, costs and efficacy of the current childhood vaccination schedule in our region.     

Epidemiology of Haemophilus influenzae invasive disease in Jamaica, 1990-1993

Haemophilus influenzae (H influenzae) invasive disease was studied retrospectively over a four-year period in children admitted to the Bustamante Hospital for Children in Kingston, Jamaica. A total of 86 cases were identified. The mean estimated annual incidence of H influenzae invasive disease in Kingston and St Andrew was 39 per 100,000 children under 5 years of age. The majority (77%) of cases were in the under 2-year age group. A distinct seasonal pattern was noted, with a significantly higher proportion of patients (57-73%) presenting in the cooler months. Meningitis was the most common clinical diagnosis, accounting for 76% of the cases. Poor outcome was demonstrated in 21.5% of patients with meningitis. Sensitivity testing of H influenzae isolates revealed a resistance rate of 26% for ampicillin and 7% for chloramphenicol. The epidemiological findings in this study provide reasonable guidelines for empiric antibiotic therapy and also support the need to seriously consider vaccine prophylaxis in Jamaican children.     

Nontypeable Haemophilus influenzae in carriage and disease: a difference in IgA1 protease activity levels

CONTEXT: Nontypeable Haemophilus influenzae strains form part of the normal flora of the human upper respiratory tract but are also implicated in a wide range of diseases. Infections caused by nontypeable H influenzae are major health and socioeconomic burdens. No single bacterial trait has been associated with disease as opposed to colonization. OBJECTIVES: To compare IgA1 protease activity in nontypeable H influenzae strains isolated from patients with symptomatic Haemophilus infection (sputum, cerebrospinal fluid, blood, or normally sterile tissue) vs strains from throat swabs of asymptomatic carriers and to compare iga gene carriage and variability in nontypeable H influenzae strains. DESIGN AND SETTING: Retrospective study of 63 strains (44 clinical and 19 carriage) collected between 1991 and 2000 and maintained at the Public Health Laboratory, Gwynedd General Hospital, Bangor, Wales. MAIN OUTCOME MEASURES: Levels of IgA1 protease activity produced by carriage strains and clinical isolates from symptomatic patients; the determination of the size and sequence of a variable region of the iga gene. RESULTS: Bacterial IgA1 protease activity was significantly higher (P<.001) in strains isolated from sputum, blood, cerebrospinal fluid, or normally sterile tissue of symptomatic individuals (median, 155 mU; interquartile range [IQR], 80-220 mU; mean, 169 mU; 95% confidence interval [CI], 126-211 mU) than in those isolated from throat swabs of asymptomatic carriers (median, 30 mU; IQR, 15-90 mU; mean, 56 mU; 95% CI, 26-86 mU; assayed on secretory IgA). The iga gene was detected in 97% of all strains examined. Variations in the sizes and sequences of part of the iga genes were also apparent. This variable region encodes a polypeptide linker connecting the protease domain to the beta-core autotranslocator, a porelike structure required for secretion of the protease. CONCLUSIONS: These findings reveal the importance of iga gene variability and expression levels in the establishment of disease phenotype. They identify nontypeable H influenzae IgA1 protease as a virulence factor and as a potential target for the development of new strategies to fight these important pathogens.     

Protective efficacy of Haemophilus influenzae type b polysaccharide and conjugate vaccines in children 18 months of age and older

To evaluate the protective efficacy of polyribosylribitol phosphate (PRP) and polyribosylribitol phosphate-diphtheria toxoid (PRP-D) vaccines in children 18 to 59 months of age, we conducted a case-control study in Los Angeles (Calif) County between July 1, 1988, and July 31, 1989. Seventy-nine children with invasive Haemophilus influenzae type b disease 18 to 59 months of age were identified, and 212 controls were selected by random-digit telephone dialing methods. Cases and controls were stratified by age and month of disease onset of the case. Seventeen PRP vaccine failures and two PRP-D vaccine failures occurred more than 2 weeks after vaccination. The PRP vaccine was shown not to be effective (point estimate--47%; 95% confidence interval,--307% to 47%), but the PRP-D vaccine was 88% protective (95% confidence interval, 42% to 97%). Adjustment of the efficacy estimates for potential confounding variables did not change the results significantly. The PRP-D vaccine provided significantly better protection than the PRP vaccine against invasive H influenzae type b disease in this population.     

Protection against recurrent acute bronchitis after oral immunization with killed Haemophilus influenzae

Subjects prone to recurrent acute bronchitis were admitted to a six-month double-blind clinical study, in which the value of oral immunization with a preparation of killed Haemophilus influenzae was tested. Most subjects had early smoking-related chronic lung disease, unrecognized by either the patient or his/her doctor. Subjects taking the active agent had a 41% reduction in the total number of episodes of acute bronchitis (P = 0.16), a 60% reduction in the number of episodes of acute wheezy bronchitis (P = 0.02) and a 58% reduction in antibiotic use (P = 0.07). The power of analysis was restricted by the small study group. Parameters of episode severity favoured the test group, suggesting that individual episodes of acute bronchitis in subjects taking an oral preparation of killed H. influenzae were less severe than in those taking placebo tablets. Oral immunization with H. influenzae selectively reduced the increase in colonization of the oropharynx with H. influenzae which occurred in the group taking placebo. This is the first demonstration that the common mucosal system can be activated to modify a colonization pattern at a distant site.     

Lack of efficacy of Haemophilus b polysaccharide vaccine in Minnesota

We evaluated the efficacy of Haemophilus b polysaccharide vaccine in children in Minnesota using a case-control study. The vaccine became available in Minnesota in August 1985. During the subsequent 28 months, 88 cases of invasive H influenzae type b disease were identified in children 24 to 71 months of age, the group targeted for vaccination. Of the 88 cases, 36 (41%) occurred in vaccinated children. Fifty-eight (33%) of 176 controls were vaccinated during a similar period. The vaccine's protective efficacy for children with any history of vaccination was -58% (95% confidence interval = -204% to 18%). The vaccine's protective efficacy for children who were most likely to be protected by vaccination was -55% (95% confidence interval = -238% to 29%). Our results indicate that vaccination with Haemophilus b polysaccharide vaccine had no effect in preventing H influenzae type b disease in Minnesota children.     

Meningitis and septicaemia in a child caused by non-typable Haemophilus influenzae biotype III.

Since vaccination against Haemophilus influenzae type b (Hib) became widespread, other strains of H. influenzae have become more common than Hib as causes of disease in vaccinated children. A four-month-old, appropriately vaccinated infant presented with meningitis and septicaemia caused by H. influenzae biotype III. To our knowledge, this is the first reported case of meningitis caused by this biotype, which is not detectable by Hib antigen tests.     

The aetiology of purulent meningitis in highland children: a bacteriological study

Of 155 highlands children with purulent culture-positive meningitis studied from March 1980 to September 1984, 84% were aged twelve months or less and 92% were infected with either Haemophilus influenzae, Streptococcus pneumoniae or both organisms. Other pathogens were Neisseria meningitidis (8 isolations), Streptococcus pyogenes (2 isolations) and Streptococcus agalactiae and Klebsiella species (1 of each). Among H. influenzae isolates, serotype b strains predominated (83%) and most (96%) belonged to biotype I or II. Infections due to non-b haemophili included serotype a (9 strains), serotype f (1 strain) and non-serotypable variants (3 strains). Of 67 S. pneumoniae strains 22% were resistant to benzylpenicillin, with minimal inhibitory concentrations of 0.1-1.0 micrograms/ml. The commonest serotypes were types 5 (11 isolates), type 7 (9 isolates) and types 2, 6 and 46 (6 of each). No resistance to chloramphenicol was detected in either H. influenzae or S. pneumoniae and only one of 56 strains of H. influenzae was insensitive to betalactam antibiotics. The known case fatality rate in this study was 37%. More children with pneumococcal infection died (46%) than those with haemophilus infection (30%), though the difference was not statistically significant; 79% of all deaths occurred in children aged less than twelve months. There is an urgent need for H. influenzae and S. pneumoniae vaccines that are effective in young children.     

Haemophilus influenzae meningitis in Manitoba and the Keewatin District, NWT: potential for mass vaccination.

A community-based surveillance study of all central nervous system infections was carried out in Manitoba and the Keewatin District, NWT, between Apr. 1, 1981, and Mar. 31, 1984. There were 201 cases of bacterial meningitis in Manitoba over the study period, 81 (40%) caused by Haemophilus influenzae; all but one isolate tested were type b (Hib). There were nine cases of H. influenzae meningitis in the Keewatin District. The overall annual incidence rate of H. influenzae meningitis in Manitoba was 2.5/100,000; for children under 5 years the rate was 32.1/100,000. For the Keewatin District the corresponding rates were 69.6/100,000 and 530/100,000. A total of 85% and 100% of the cases of H. influenzae meningitis occurred by 24 months of age in Manitoba and the Keewatin District respectively. The age at onset was earlier in native Indian children (22 cases) and Inuit children (9 cases) than in non-native children (59 cases) (p less than 0.005); thus, vaccine prevention of Hib meningitis will likely be more difficult in native Indian and Métis children. Without evaluating the increased potential of H. influenzae vaccines to prevent nonmeningitic forms of disease, we concluded that mass childhood vaccination with polyribosylribitolphosphate (PRP) vaccine is not warranted in Manitoba or the Keewatin District. Immunogenicity studies suggest that administration of conjugated Hib vaccines such as PRP-D in infancy may prevent approximately one-third to two-thirds of cases of H. influenzae meningitis; these vaccines warrant consideration for use in mass childhood vaccination programs.     

Effect of immunoglobulin on hepatitis A in day-care centers

Over a 21-month interval, we investigated the effectiveness of immunoglobulin (lg) in preventing hepatitis A spread in day-care centers. Immunoglobulin was given to all center and employees whenever hepatitis occurred in one center child or employee or parents in two families. Immunoglobulin programs were completed in 91 centers during the trial within an average of 17 days of onset of illness in the index case. Immunoglobulin intervention caused significant reduction in the average size of a day-care hepatitis outbreaks, from 7.3 cases in historically untreated centers to 6.0 cases in Ig-treated centers. Cases in center children and employees virtually ceased two weeks after Ig intervention, while those in household contacts decreased significantly within six weeks. Reported cases of hepatitis type A or unspecified in the community decreased 75%, and the number of new hepatitis outbreaks decreased 77% during the trial. A decrease occurred not only in day-care-associated cases, but in cases not directly associated with centers, probably due to decreased tertiary spread from day-care families into the community. Use of Ig to prevent hepatitis spread in day-care centers seems to be an excellent means of controlling this disease, both within the centers and the general community.     

Bacterial meningitis in children under five years of age in Western Australia

OBJECTIVES: To describe the epidemiology and the associated mortality and serious neurological sequelae of bacterial meningitis in children under five years of age in Western Australia, and to consider the potential impact of a Haemophilus influenzae type b vaccine on this group of children. DESIGN: A retrospective survey, using multiple sources of case ascertainment. PATIENTS: All children in Western Australia from one month to five years of age who developed bacterial meningitis, over a five-year period (from 1984 to 1988 inclusive). MAIN OUTCOME MEASURES: Episodes of bacterial meningitis, deaths associated with bacterial meningitis, and sensorineural deafness (requiring hearing aids) and cerebral palsy following bacterial meningitis. RESULTS: Two hundred and seventy episodes of bacterial meningitis were identified; 200 occurred in non-Aboriginal children and 70 in Aboriginal children. There were 16 meningitis-associated deaths (case fatality rate, 5.9%), 7 children developed profound sensorineural deafness and a further 7 children developed cerebral palsy after bacterial meningitis. H. influenzae type b caused nearly 70% of the cases of childhood bacterial meningitis. The annual incidence rate of H. influenzae meningitis was significantly greater in Aboriginal children (150 episodes per 100,000 children under five years of age per year) than in non-Aboriginal children (27 episodes per 100,000), and the mean age of onset of H. influenzae meningitis was significantly lower in Aboriginal children (6.8 months) than in non-Aboriginal children (19.8 months). CONCLUSIONS: Any conjugate H. influenzae type b vaccine should be effective when administered to non-Aboriginal children in the first six months of life, but only the most immunogenic vaccines (for example, the vaccine known as PRP-OMP) are likely to be effective in Aboriginal infants.     

Haemophilus influenzae meningitis in school-aged children

The relative frequency of meningitis caused by Haemophilus influenzae in school-age children was determined by reviewing etiologic diagnoses in children 6 to 15 years old admitted to four hospitals from 1974 to 1978. Sixty-five (45%) of 145 patients had aseptic meningitis and 29 (20%) had bacterial meningitis. Thirty-two (22%) of the patients had received antibiotic therapy before diagnosis, and 19 (13%) could not be classified. Six (21%) of the 29 patients with bacterial meningitis had H influenzae meningitis. Although aseptic disease was the most common type of meningitis, initial antibiotic therapy for presumed bacterial meningitis in school-aged children should include adequate coverage for H influenzae.