Presence of Antibodies Against Haemophilus influenzae Serotype a in Alaska Before and After the Emergence of Invasive Infections

Abstract Background Haemophilus influenzae bacteria can cause asymptomatic carriage and invasive disease. Haemophilus influenzae serotype a (Hia) is an emerging cause of invasive disease in Alaska, with greatest burden occurring among rural Alaska Native (AN) children. The first case of invasive Hia (iHia) in Alaska was reported in 2002; however, it is unclear how long the pathogen has been in Alaska. Methods We quantified immunoglobulin G antibodies against Hia (anti-Hia) in 839 banked serum samples from Alaska residents, comparing antibody concentrations in samples drawn in the decades before (1980s and 1990s) and after (2000s) the emergence of iHia. We also assessed serum antibody concentration by age group, region of residence, and race. Results The anti-Hia was >0.1 µg/mL in 88.1% (348 of 395) and 91.0% (404 of 444) of samples from the decades prior and after the emergence of Hia, respectively (P = .17). No significant differences in antibody levels were detected between people from rural and urban regions (1.55 vs 2.08 µg/mL, P = .91 for age ≥5) or between AN and non-AN people (2.50 vs 2.60 µg/mL, P = .26). Conclusions Our results are consistent with widespread Hia exposure in Alaska predating the first iHia case. No difference in Hia antibody prevalence was detected between populations with differing levels of invasive disease.

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Pediatric invasive disease due to Haemophilus influenzae serogroup A in Riyadh, Saudi Arabia: case series

The Journal of Infection in Developing Countries ◽

10.3855/jidc.6687 ◽

2016 ◽

Vol 10 (05) ◽

pp. 528-532 ◽

Cited By ~ 2

Author(s):

Zailaie Roaa ◽

Alawfi Abdulsalam ◽

Ghazi Shahid ◽

Baba Kamaldeen ◽

Al Fawaz Tariq

Keyword(s):

Saudi Arabia ◽

Blood Culture ◽

Haemophilus Influenzae ◽

Vaccine Development ◽

Good Condition ◽

Case Series ◽

Invasive Disease ◽

Medical Illness ◽

Serotype A ◽

First Case

We describe the first two cases of invasive disease caused by Haemophilus influenzae serotype A in Saudi Arabia. This is the first known reported invasive Haemophilus influenzae serotype A from Saudi Arabia. Case presentation: A ten-month-old and three-month-old male not known to have any past history of any medical illness and who had received H. influenzae type b (Hib) vaccine presented to our hospital mainly with fever of few days’ duration. A provisional diagnosis of meningitis with sepsis was made and laboratory tests were requested. The chest radiograph was normal. The laboratory results revealed leukocytosis, but leukopenia was noticed in the younger infant. Blood culture and cerebrospinal fluid specimens yielded a pure culture of Haemophilus influenzae and serotyping showed the isolates to be serogroup A. Both patients were started on vancomycin and third-generation cephalosporin. On receiving the blood culture result, vancomycin was stopped. Fever subsided after 48 hours, while in the second case, it continued for 12 days from the admission date. The repeat blood cultures were negative. Antibiotic therapy was given for 10 days for the first case with an unremarkable hospital course, while the second case was complicated by seizure and received a longer duration of antibiotics. Both infants were discharged home in good condition. Conclusions: Invasive non-typeable H. influenzae strains are emerging and there is a need for surveillance of this disease. This has implications in future vaccine development.

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Epidemiology of Invasive Haemophilus influenzae Serotype a Disease—United States, 2008–2017

Clinical Infectious Diseases ◽

10.1093/cid/ciaa875 ◽

2020 ◽

Author(s):

Heidi M Soeters ◽

Sara E Oliver ◽

Ian D Plumb ◽

Amy E Blain ◽

Tammy Zulz ◽

...

Keyword(s):

United States ◽

Haemophilus Influenzae ◽

Alaska Native ◽

Disease Surveillance ◽

Vaccine Development ◽

Case Fatality ◽

The United States ◽

Invasive Disease ◽

Bacterial Disease ◽

Serotype A

Abstract Background Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008–2017. Methods Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated. Results From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN. Conclusions Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development.

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Immunogenicity of Haemophilus influenzae Type b Polysaccharide-Neisseria meningitidis Outer Membrane Protein Conjugate Vaccine in 2- to 6-Month-Old Infants

PEDIATRICS ◽

10.1542/peds.80.2.283 ◽

1987 ◽

Vol 80 (2) ◽

pp. 283-287

Author(s):

Allen A. Lenoir ◽

Paul D. Granoff ◽

Dan M. Granoff

Keyword(s):

Membrane Protein ◽

Haemophilus Influenzae ◽

Neisseria Meningitidis ◽

Outer Membrane Protein ◽

Geometric Mean ◽

Serum Antibody ◽

Haemophilus Influenzae Type ◽

Antibody Concentration ◽

Haemophilus Influenzae Type B ◽

Type B

Fifty infants, 2 to 6 months of age, were vaccinated with Haemophilus influenzae type b capsular polysaccharide covalently linked to an outer membrane protein from Neisseria meningitidis group B. Subjects were given two injections and were randomly assigned to receive the injections separated by 1 or 2 months. Each dose contained 15 µg of polysaccharide and 51 µg of protein, or approximately twice the amount of polysaccharide as used in our previous trial (Lancet 1986;2:299). Fevers of 38.0° to 38.8°C developed in three infants (6%) within 24 hours after vaccination, but there were no other notable reactions. Following one injection, the geometric mean antibody concentration increased from 0.13 µg/mL in preimmune serum to 1.50 µg/mL in serum obtained 1 to 2 months later (P < .001). After a second injection, there was a further increase in serum antibody (geometric mean = 3.11 µg/mL, P < .007). The geometric mean antibody concentration of the group reimmunized 2 months after the first injection was higher than that in the group reimmunized after 1 month (3.95 v 2.32 µg/mL, P = .05, by analysis of covariance with age as the covariant). These data confirm our previous preliminary observations on the safety and immunogenicity of this new conjugate vaccine in infants 2 to 6 months of age. The data suggest that a 2-month interval between the first and second injections results in higher levels of serum antibody than a 1-month interval.

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Interchangeability of Haemophilus influenzae Type b vaccines in the Primary Series: Evaluation of a Two-dose Mixed Regimen

PEDIATRICS ◽

10.1542/peds.98.5.898 ◽

1996 ◽

Vol 98 (5) ◽

pp. 898-904 ◽

Cited By ~ 1

Author(s):

Kathleen M. Bewley ◽

Joel G. Schwab ◽

Gerard A. Ballanco ◽

Robert S. Daum

Keyword(s):

Haemophilus Influenzae ◽

Randomized Clinical Trials ◽

Geometric Mean ◽

Serum Antibody ◽

Area Under The Curve ◽

Haemophilus Influenzae Type ◽

Antibody Concentration ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Series Evaluation

Objective. To evaluate two- or threedose "mixed" regimens of Haemophilus influenzae type b conjugate vaccines in the priming series. Design. Two randomized clinical trials with 140 and 181 infants, respectively. Setting. Private practices in New Orleans and Chicago. Methods. In trial I, infants received one of four regimens. Two were recommended regimens for polyribosylribitol phosphate (PRP)—meningococcal protein conjugate (M) and PRP—tetanus toxoid conjugate (T). Two mixed regimens consisted of M at 2 months followed by two doses of T or PRP—diphtheria toxoid conjugate (D) at 4 and 6 months. Trial II consisted of three groups. Two were recommended regimens for M and T. The third was a two-dose mixed regimen consisting of M at 2 months and T at 4 months. Parents were interviewed and instructed to record side effects after each vaccination. Serum was assayed for H influenzae type b anticapsular antibody (anti-PRP). Results. Minor differences in safety profiles likely reflected α error. In trial I, M (lot 0884T, one of several known to have had decreased immunogenicity), probably primed for substantial increase in serum antibody when D or T was given at 4 and 6 months. In trial II, infants who received the two-dose mixed regimen (M from immunogenic lot 0116W at 2 months and T at 4 months) had a significantly higher mean area under the curve than recipients of the three-dose TIT regimen when antibody concentration was plotted against age, although the geometric mean anti-PRP antibody concentration for the MT-recipients was significantly lower at 7 months. Conclusions. M used in trial I may have primed infants despite poor immunogenicity. The two-dose mixed regimen (MT-) in trial II produced a mean anti-PRP antibody concentration with higher sustained anti-PRP concentrations from 2 to 7 months, as judged by the area under the curve, but a lower mean anti-PRP antibody concentration at 7 months.

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First Complete Genome Sequence of Haemophilus influenzae Serotype a

Genome Announcements ◽

10.1128/genomea.01506-16 ◽

2017 ◽

Vol 5 (3) ◽

Cited By ~ 3

Author(s):

Mariam Iskander ◽

Kristy Hayden ◽

Gary Van Domselaar ◽

Raymond Tsang

Keyword(s):

Haemophilus Influenzae ◽

Genome Sequence ◽

Invasive Disease ◽

Indigenous Populations ◽

Whole Genome Sequence ◽

Whole Genome ◽

Human Pathogen ◽

Small Children ◽

Content Type ◽

Serotype A

ABSTRACT Haemophilus influenzae is an important human pathogen that primarily infects small children. In recent years, H. influenzae serotype a has emerged as a significant cause of invasive disease among indigenous populations. Here, we present the first complete whole-genome sequence of H. influenzae serotype a.

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A Competitive Enzyme-Linked Immunosorbent Assay for Measuring the Levels of Serum Antibody to Haemophilus influenzae Type b

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.5.5.667-674.1998 ◽

1998 ◽

Vol 5 (5) ◽

pp. 667-674 ◽

Cited By ~ 15

Author(s):

Massimo Mariani ◽

Enrico Luzzi ◽

Daniela Proietti ◽

Silvia Mancianti ◽

Daniele Casini ◽

...

Keyword(s):

Haemophilus Influenzae ◽

Capsular Polysaccharide ◽

Regression Line ◽

Serum Antibody ◽

Competitive Elisa ◽

Haemophilus Influenzae Type ◽

Enzyme Linked Immunosorbent Assay ◽

Type B ◽

Elisa Method ◽

Serum Samples

ABSTRACT A competitive ELISA method is described for the measurement of total antibodies to the capsular polysaccharide ofHaemophilus influenzae type b (HibCPS) in human sera. The competitive method showed an excellent correlation to the radioantigen binding assay (RABA, or Farr assay) and improved correlation of sera with low titers with respect to the more conventional noncompetitive method. Overestimation of samples in the low concentration range was no longer observed with the competitive ELISA method. The free HibCPS competition allowed us to eliminate the day-to-day background variation typical of some sera; thus, only values representing the true anti-HibCPS response were determined. The use of precoated microplates, which could be stored up to 8 months, greatly improved the speed of the procedure. An overall correlation coefficient of 0.9660 was found when 407 serum samples with a wide variety of anti-HibCPS antibody levels were tested with the competitive ELISA and RABA. The regression line was very close to the ideal line, with a slope of 1.0045 and an intercept of −0.1996. A subset of 96 serum samples representative of all pre- and postimmunization samples was used to compare the competitive ELISA with a previously described ELISA method. The competitive method performed in two laboratories in different countries showed a better correlation with the RABA. The correlation factors were 0.9770 and 0.9816, respectively, while a factor of 0.9547 was found with the previously described noncompetitive procedure, which was better for this method than previously reported (r = 0.917). Therefore, the competitive ELISA is proposed for the assay of anti-HibCPS titers in sera from vaccinated subjects.

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Septic arthritis and hemarthroses caused by Haemophilus influenzae serotype A in children

Infectious Disease Reports ◽

10.4081/idr.2016.6494 ◽

2016 ◽

Vol 8 (3) ◽

Author(s):

Ravi S. Samraj ◽

Jaime Fergie

Keyword(s):

Respiratory Tract ◽

Haemophilus Influenzae ◽

Septic Arthritis ◽

Respiratory Tract Infections ◽

Invasive Disease ◽

Serotype A ◽

Clinical Syndromes ◽

Tract Infections

Invasive disease caused by <em>Haemophilus influenzae</em> serotype A (Hia) is rare in children. Clinical syndromes caused by Hia include meningitis, sepsis and respiratory tract infections. Septic arthritis is rare in children with invasive Hia infection and hemarthrosis has not been described in the published literature. We report a case of septic arthritis and hemarthrosis caused by Hia infection in a 2.5 year-old-boy and review invasive Hia infection in children.

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Invasive Disease Caused by Haemophilus Influenzae Serotype a, an Emerging Pathogen in Alaska.

International Journal of Epidemiology ◽

10.1093/ije/dyv096.308 ◽

2015 ◽

Vol 44 (suppl_1) ◽

pp. i195-i195

Author(s):

M. G. Bruce ◽

T. Zulz ◽

C. Debyle ◽

R. Singleton ◽

D. Hurlburt ◽

...

Keyword(s):

Haemophilus Influenzae ◽

Invasive Disease ◽

Emerging Pathogen ◽

Serotype A

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Dynamics of natural immunity caused by subclinical infections, case study on Haemophilus influenzae type b (Hib)

Epidemiology and Infection ◽

10.1017/s0950268800004799 ◽

2000 ◽

Vol 125 (3) ◽

pp. 583-591 ◽

Cited By ~ 12

Author(s):

T. LEINO ◽

K. AURANEN ◽

P. H. MÄKELÄ ◽

H. KÄYHTY ◽

A. K. TAKALA

Keyword(s):

Haemophilus Influenzae ◽

Invasive Disease ◽

Haemophilus Influenzae Type ◽

Antibody Concentration ◽

Natural Immunity ◽

Type B ◽

Force Of Infection ◽

Invasive Infections ◽

Disease Antibody ◽

Antibody Levels

Natural immunity to Haemophilus influenzae type b (Hib) is based primarily on antibodies that are thought to develop in response to subclinical infections. Wide use of conjugated Hib vaccines could lead to decreases in circulating Hib bacteria, thereby diminishing antibody levels in the unvaccinated. We applied a statistical model to estimate the duration of natural immunity to Hib under different forces of infection. Prior to the introduction of conjugated Hib vaccines, new Hib infections were estimated to occur once in 4 years and the antibody concentration to stabilize at a level around 1 μg/ml. In the absence of new stimuli, i.e. infection, 57% of the unvaccinated population would become susceptible to invasive disease (antibody levels < 0·15 μg/ml) in 10 years. Due to an interaction between the force of infection and the duration of immunity, in some situations numbers of invasive infections could increase in unvaccinated cohorts. This theoretical scenario has yet to be observed in practice.

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