Appearance of new strains after vax with HIB vax

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repeat - Appearance of new strains after vax with HIB vax

http://bmj.bmjjournals.com/cgi/content/full/312/7024/160

increase in non-type b strains - they like to explain it away - but

this is what we have seen - decrease in one type and increase in

another - nature abhors a vacuum?

BMJ 1996;312:160-161 (20 January)

Papers

Changing patterns of invasive Haemophilus influenzae disease in

England and Wales after introduction of the Hib vaccination programme

Ruth M Hargreaves, senior registrar in microbiology,a P E Slack,

senior lecturer in microbiology,a J , director,b Eileen

, medical laboratory scientific officer,a E Ramsay,

consultant epidemiologist c

a Haemophilus Reference Unit, Oxford Public Health Laboratory,

Radcliffe Hospital, Headington, Oxford OX3 9DU, b Gwynedd Public

Health Laboratory, Bangor, North Wales, c Public Health Laboratory

Service, Communicable Disease Surveillance Centre, London NW9 5EQ

Correspondence to: Dr Hargreaves.

Since 1990 we have been monitoring strains of Haemophilus influenzae

referred to the Public Health Laboratory Service Haemophilus

Reference Laboratories from all cases of invasive H influenzae

disease from five English regions and Wales. Methods of reporting and

participating laboratories have remained constant over this period,

which allowed us to compare the incidence of infection before and

after the introduction of vaccination against H influenzae type b in

October 1992.

Patients, methods, and results

The case definition was a systemic infection in which culture of

normally sterile body fluid revealed H influenzae, or the organism

was detected by antigen to H influenzae type b. Organisms were

identified and typed at the reference laboratories using both type

specific antisera and a polymerase chain reaction method.1 Brief

clinical details were also collected. The results for the first two

years of the survey showed that most H influenzae infections were due

to type b, presented as meningitis, and occurred in children under

5,2 suggesting that mass vaccination of infants should achieve a

rapid change in the pattern of invasive H influenzae infections.

Since October 1992 there has been a rapid reduction in the number of

reported cases of H influenzae type b disease, particularly in

children aged under 5 (see figure). Annual attack rates for H

influenzae type b disease in children under 5 (calculated using

denominator populations) have fallen from 30.9 cases per 100000

population in 1991-2 (369 cases recorded) to 2.0 per 100000 in 1993-4

(24 cases), a reduction in risk of invasive disease from 1 case in

3200 to 1 per 50000 children. Comparison of the rates of invasive H

influenzae type b disease in children under 5 using log-linear

regression showed a highly significant reduction (P<0.001 in 1993-4

compared with previous years).

Non-capsulate H influenzae isolates have shown an increase in annual

attack rate (for all ages) from 0.25 cases per 100000 population in

1990-1 (45 cases recorded) to 0.37 in 1993-4 (67 cases). The total

number of recorded cases of non-type b infections (non-capsulate and

other serotypes: 75 cases) exceeded the number of cases of H

influenzae type b (50 cases) in 1993-4. These increases demonstrate a

sustained trend, approaching significance for non-capsulate

infections during 1993-4 (P=0.066), which has been most noticeable in

people aged over 65 years.

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Invasive H influenzae type b and non-capsulate infections by quarter

Comment

These findings show the expected rapid reduction in the numbers of

invasive H influenzae type b infections after the introduction of

vaccination. The rate of decline has closely followed the increase in

vaccine coverage and has been greatest in children aged under 5. This

survey suggests that the United Kingdom vaccination schedule has been

as effective at reducing numbers of cases as those schedules adopted

in the USA3 4 and northern European countries.5 The increase in

non-type b strains may reflect improved case ascertainment, perhaps

because of increased awareness of haemophilus disease after the

vaccination campaign. Nevertheless, there is a need to continue to

monitor all invasive infections to determine whether these trends

will be maintained in both the vaccinated and unvaccinated populations.

This survey was coordinated by the haemophilus working group of the

Public Health Laboratory Service. We acknowledge the help of all

contributing microbiologists, the regional coordinating

microbiologists, and the staff at the haemophilus reference units in

Oxford and Bangor. Dr Paddy Farrington gave statistical advice and Dr

Mayon-White read the manuscript.

Funding: Haemophilus working group.

Conflict of interest: None.

1. Slack MPE, Crook DWM, Jordens JZ, EC, Falla T, Leaves

NI, et al. Molecular and epidemiological aspects of Haemophilus

influenzae infection. PHLS Microbiology Digest 1993;10:122-8.

2. EC, Begg NT, Crawshaw SC, Hargreaves RM, AJ,

Slack MPE. Epidemiology of invasive Haemophilus influenzae in the

pre-vaccination era. Epidemiol Infect 1995;115:89-100. [Medline]

3. American Academy of Pediatrics. Haemophilus influenzae type b

conjugate vaccines: Recommendations for immunization of infants and

children 2 months of age and beyond. Paediatrics 1991;88:169-72. [Medline]

4. WG, Deaver KA, Cochi SL, Plikaytis BD, Zell ER, Broome

CV, et al. Decline of childhood. Haemophilus influenzae type b (Hib)

disease in the Hib vaccine era. JAMA 1993;269:221-6. [Abstract]

5. Peltola H, Kilpi T, Anttila M. Rapid disappearance of

Haemophilus influenzae type b meningitis after routine childhood

immunisation with conjugate vaccines. Lancet 1992;340:592-4. [Medline]

(Accepted 1 November 1995)

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" there was a relative increase of nontypeable strains from 3 to 6.6%

(P = 0.27). "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed & cmd=Retrieve & list_uids=8\

904414 & dopt=Abstract

J Clin Microbiol. 1996 Mar;34(3):560-3. Related Articles, Links

Click here to read Click here to read

Molecular characteristics of Haemophilus influenzae causing

invasive disease during the period of vaccination in Switzerland:

analysis of strains isolated between 1986 and 1993.

Muhlemann K, Balz M, Aebi S, Schopfer K.

Institute of Medical Microbiology, University of Berne,

Switzerland. muehlemann@...

The broad use of conjugated vaccines against Haemophilus

influenzae type b may select for strains to which the polysaccharide

vaccine does not provide immunity. We analyzed 392 consecutive H.

influenzae isolates from Swiss children 0 to 16 years of age with

invasive disease during the years 1986 to 1993. Bacterial strains

were characterized by serotyping, capsular genotyping, outer membrane

protein (OMP) subtyping, and ribotyping. Of 392 strains, 372 were

serotype b, 1 was serotype a, 3 were serotype f, and 16 were

nontypeable H. influenzae. After the introduction of Haemophilus

conjugate vaccines in 1990, there was a relative increase of

nontypeable strains from 3 to 6.6% (P = 0.27). Of the type b strains,

281 (75.5%) had the same OMP subtype and ribotype pattern. This clone

predominated in the pre- and postvaccine periods. After the year

1990, the proportions of OMP subtype 1c and OMP subtype 3 tended to

increase. Isolates from previously vaccinated (n = 10) and

nonvaccinated patients did not differ in their subtype distributions.

We conclude that the administration of conjugated vaccines decreased

invasive disease caused by the most prevalent H. influenzae type b

clone. However, further surveillance of circulating H. influenzae

strains during the period of vaccination is indicated.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed & cmd=Retrieve & list_uids=8\

589168 & dopt=Abstract

Increase in other strains - an increase in infection due to non-type

b serotypes of H. influenzae

Clin Infect Dis. 1995 Nov;21(5):1322-4. Related Articles, Links

The emergence of Haemophilus influenzae types e and f as

significant pathogens.

Waggoner-Fountain LA, Hendley JO, Cody EJ, Perriello VA, Donowitz LG.

Department of Pediatrics, University of Virginia Health Sciences

Center, Charlottesville 22908, USA.

Non-type b encapsulated Haemophilus influenzae meningitis (two

cases due to H. influenzae type e, two due to H. influenzae type f)

was diagnosed in four children in a 6-month period at the University

of Virginia. H. influenzae type b was the most common cause of

bacterial meningitis in the United States before the introduction of

an effective vaccine, whereas the other five encapsulated serotypes

of H. influenzae rarely caused invasive disease. The clinical

features of non-type b H. influenzae meningitis and the therapy for

this infection are the same as those for type b H. influenzae

disease. We report these four cases to document an increase in

infection due to non-type b serotypes of H. influenzae, and we

postulate that this change may result from the well-documented

decrease in H. influenzae type b oropharyngeal carriage and disease

that has occurred because of universal vaccination for H. influenzae type b.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed & cmd=Retrieve & list_uids=3\

10538 & dopt=Abstract

" " Serious infections caused by other H. influenzae types will

continue to occur sporadically and may increase in frequency when an

effective vaccine against type b is widely used in infants. " "

Pediatrics. 1978 Dec;62(6):1021-5. Related Articles, Links

Meningitis due to Haemophilus influenzae other than type b: case

report and review.

Greene GR.

A 4-month-old female infant with meningitis caused by

Haemophilus influenzae type f had a hospital course complicated by

sterile subdural effusions and persistent neurologic abnormalities.

One year later she was normal in all respects. The infant's mother

had serum bactericidal antibodies to H. influenzae type b but not to

type f. During recovery the patient had no bactericidal antibodies to

type b, and the type f organism could not be maintained in her serum.

Review of the literature identified 40 cases of meningitis reported

as caused by H. influenzae other than type b. An evaluation of the

ten cases described as due to encapsulated strains (a, e, and f)

shows that the age distribution and clinical features are similar to

those of meningitis caused by type b. Only five cases of meningitis

caused by unencapsulated H. influenzae have been described. Four of

the patients were older than the usual age range for type b

meningitis and two had prior head trauma. A large clinical trial in

Finland with a two-year observation period has demonstrated no

untoward increase in non-b H. influenzae meningitis in recipients of

a type b vaccine. Serious infections caused by other H. influenzae

types will continue to occur sporadically and may increase in

frequency when an effective vaccine against type b is widely used in infants.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed & cmd=Retrieve & list_uids=9\

568952 & dopt=Abstract

J Paediatr Child Health. 1998 Feb;34(1):95-6. Related Articles, Links

Meningitis due to Haemophilus influenzae type f.

Pincus DR, Robson JM.

Allamanda Medical Centre, Southport, Queensland, Australia.

OBJECTIVE: To describe a case of Haemophilus influenzae type f

(Hif) meningitis occurring in the H. influenzae type b (Hib) vaccine

era. RESULTS: Successful treatment of a case of Hif meningitis in a

previously vaccinated 3-year-old girl is described. The outcome was

complicated by deafness. No underlying immunosuppression was

demonstrated. CONCLUSIONS: Despite the great success of Hib vaccines

in reducing invasive disease due to H. influenzae, cases of H.

influenzae meningitis continue to occur, caused by less common

encapsulated serotypes. Whether there will be an increase in the

number of these cases in the vaccine era is unknown and infection due

to non-b serotypes requires close monitoring.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed & cmd=Retrieve & list_uids=8\

783712 & dopt=Abstract

" Again, increase in other types. " With the decline in the rate of

infections caused by Haemophilus influenzae serotype b, H. influenzae

serotype f (Hif) is becoming a relatively important cause of invasive

disease due to H. influenzae. " "

Clin Infect Dis. 1996 Jun;22(6):1069-76. Related Articles, Links

Comment in:

* Clin Infect Dis. 1996 Jun;22(6):1077-8.

Invasive disease due to Haemophilus influenzae serotype f:

clinical and epidemiologic characteristics in the H. influenzae

serotype b vaccine era. The Haemophilus influenzae Study Group.

Urwin G, Krohn JA, Deaver- K, Wenger JD, Farley MM.

Department of Medicine, Veterans Administration Medical Center,

Decatur, Georgia 30033, USA.

With the decline in the rate of infections caused by Haemophilus

influenzae serotype b, H. influenzae serotype f (Hif) is becoming a

relatively important cause of invasive disease due to H. influenzae.

We identified 91 cases of invasive Hif infections in a multistate

area over a 6-year period. The incidence of invasive Hif disease was

0.5 case per 1,000,000 population in 1989 and 1.9 cases per 1,000,000

population in 1994. The proportion of all invasive H. influenzae

disease caused by Hif rose from 1% in 1989 to 17% in 1994.

Seventy-two percent of cases occurred in adults, and 26% of cases

occurred in children younger than 5 years of age. Respiratory tract

infections accounted for 82% of adult cases, and most adults had

significant underlying diseases. In children, pneumonia and

meningitis each accounted for 40% of cases, respectively. Overall

mortality was 30% among adults, and 21% among children. Molecular

typing demonstrated limited overall diversity in Hif isolates.

Continued surveillance is warranted to evaluate the trend toward the

increasing incidence of Hif disease that was noted in this study.