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Serotypes Changing As A Result of Vaccination

Vaccination News Home Page

Serotypes Changing As A Result of Vaccination


Challenges for the development of vaccines against Haemophilus influenzae and Neisseria meningitidis

Successful vaccines exist for type b (but not nontypeable) Haemophilus influenzae and to some (but not all) serotypes of Neisseria meningitidis; completing the 'set' of vaccines presents a major challenge.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12508153&dopt=Abstract

 
J Infect Dis. 2003 Jan 1;187(1):109-16. Epub 2002 Dec 13. Related Articles, Links
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Prevention of Haemophilus influenzae type b (Hib) meningitis and emergence of serotype replacement with type a strains after introduction of Hib immunization in Brazil.

Ribeiro GS, Reis JN, Cordeiro SM, Lima JB, Gouveia EL, Petersen M, Salgado K, Silva HR, Zanella RC, Almeida SC, Brandileone MC, Reis MG, Ko AI.

Goncalo Moniz Research Center, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Bahia, Brazil.

Surveillance for Haemophilus influenzae meningitis cases was performed in Salvador, Brazil, before and after introduction of H. influenzae type b (Hib) immunization. The incidence of Hib meningitis decreased 69% during the 1-year period after initiation of Hib immunization (from 2.62 to 0.81 cases/100,000 person-years; P<.001). In contrast, the incidence for H. influenzae type a meningitis increased 8-fold (from 0.02 to 0.16 cases/100,000 person-years; P=.008). Pulsed-field gel electrophoretic analysis demonstrated that H. influenzae type a isolates belonged to 2 clonally related groups, both of which were found before Hib immunization commenced. Therefore, Hib immunization contributed to an increased risk for H. influenzae type a meningitis through selection of circulating H. influenzae type a clones. The risk attributable to serotype replacement is small in comparison to the large reduction in Hib meningitis due to immunization. However, these findings highlight the need to maintain surveillance as the use of conjugate vaccines expands worldwide.

PMID: 12508153 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12567299&dopt=Abstract

 
Clin Infect Dis. 2003 Feb 15;36(4):422-8. Epub 2003 Jan 30. Related Articles, Links
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Serotype distribution, antibiotic susceptibility, and genetic relatedness of Neisseria meningitidis strains recently isolated in Italy.

Mastrantonio P, Stefanelli P, Fazio C, Sofia T, Neri A, La Rosa G, Marianelli C, Muscillo M, Caporali MG, Salmaso S.

Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanita, Rome, Italy. pmastran@iss.it

The availability of new polysaccharide-protein conjugate vaccines against Neisseria meningitidis serogroup C prompted European National Health authorities to carefully monitor isolate characteristics. In Italy, during 1999-2001, the average incidence was 0.4 cases per 100,000 inhabitants. Serogroup B was predominant and accounted for 75% of the isolates, followed by serogroup C with 24%. Serogroup C was isolated almost twice as frequently in cases of septicemia than in cases of meningitis, and the most common phenotypes were C:2a:P1.5 and C:2b:P1.5. Among serogroup B meningococci, the trend of predominant phenotypes has changed from year to year, with a recent increase in the frequency of B:15:P1.4. Only a few meningococci had decreased susceptibility to penicillin, and, in the penA gene, all of these strains had exogenous DNA blocks deriving from the DNA of commensal Neisseria flavescens, Neisseria cinerea, and Neisseria perflava/sicca. Fluorescent amplified fragment-length polymorphism analysis revealed the nonclonal nature of the strains with decreased susceptibility to penicillin.

PMID: 12567299 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12064693&dopt=Abstract

 
Scand J Infect Dis. 2002;34(4):289-98. Related Articles, Links

The changing epidemiology of bacterial meningitis and invasive non-meningitic bacterial disease in scotland during the period 1983-99.

Kyaw MH, Christie P, Jones IG, Campbell H.

Public Health Sciences, University of Edinburgh, UK. Moe.Kyaw@scieh.csa.scot.nhs.uk

We reviewed population-based laboratory reports of invasive meningococcal, pneumococcal, Haemophilus influenzae, Group B Streptococcus (GBS) and Listeria monocytogenes isolates in order to examine the changing epidemiology of meningitis and invasive non-meningitic disease (INMD) caused by these 5 pathogens in the 2 periods before (1983-91) and after (1992-99) routine use of H. influenzae type B conjugate vaccine (Hib) in Scotland. Neissieria meningitidis was the most common cause of meningitis, accounting for 39.2% of cases of meningitis in 1983-91 and 47% of cases in 1992-99, followed by H. influenzae (31%), Streptococcus pneumoniae (22.4%), GBS (3.9%) and L. monocytogenes (3.5%) in 1983-91 and S. pneumoniae (36.3%), H. influenzae (7.8%), GBS (6.1%) and L. monocytogenes (2.8%) in 1992-99. The important epidemiological features of meningitis and INMD caused by these 5 pathogens between 1983-91 and 1992-99 include: 1. The incidence of bacterial meningitis due to S. pneumoniae and GBS was stable; 2. S. pneumoniae was the predominant cause of INMD in both periods; 3. The incidences of INMD caused by N. meningitidis, GBS and S. pneumoniae increased, by 27%, 55% and 56%, respectively; 4. Decreases in the incidences of bacterial meningitis (by 50%) and INMD (by 50%) due to L. monocytogenes were detected; and 5. There were dramatic reductions in the proportions of bacterial meningitis (by 92%) and INMD (by 56%) due to H. influenzae in vaccinated and non-vaccinated individuals. Continued surveillance is necessary to monitor the disease trend, population at risk, serotype distribution and antimicrobial susceptibility in order to implement appropriate public health interventions against invasive bacterial disease.

PMID: 12064693 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12556429&dopt=Abstract

 
J Antimicrob Chemother. 2002 Dec;50 Suppl S2:13-9. Related Articles, Links
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Antimicrobial susceptibility and pneumococcal serotypes.

Fenoll A, Asensio G, Jado I, Berron S, Camacho MT, Ortega M, Casal J.

Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Ctra Majadahonda-Pozuelo, km. 2, 28220 Majadahonda, Madrid, Spain. afenoll@isciii.es

The increase in antibiotic resistance and the possible changes in serotype prevalence as a consequence of a new conjugated vaccine have contributed to renewed interest in the study of pneumococcal serotypes and their antibiotic resistances. Spain still has one of the highest penicillin resistance rates, but in the past 4-5 years a slight decrease has been observed. The level of resistance has not increased either, 12.7% of the 11 165 isolates studied showed high-level penicillin resistance but 94% of these had an MIC of only 2 mg/L. Serotypes 6, 9, 14, 19 and 23 included 83% of the penicillin-resistant pneumococci; the remaining 17% belonged to 18 different serotypes. We analysed these minor penicillin-resistant serotypes in view of their potential increase following a possible child vaccination programme. Four of these serotypes (11, 15, 21 and 35) were the most prevalent, and among them serotype 15 was particularly frequent with >50% of its strains resistant. The effective control of these minor penicillin-resistant serotypes should be based on continuous surveillance of pneumococcal epidemiology.

PMID: 12556429 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11923343&dopt=Abstract

 
J Clin Microbiol 2002 Apr;40(4):1264-70 Related Articles, Links
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Limited genetic diversity of recent invasive isolates of non-serotype b encapsulated Haemophilus influenzae.

Omikunle A, Takahashi S, Ogilvie CL, Wang Y, Rodriguez CA, St Geme JW 3rd, Adderson EE.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Invasive infections caused by non-type b encapsulated Haemophilus influenzae have increased in frequency in the last decade. This change prompted us to characterize the genetic relationships of 48 recently isolated invasive H. influenzae type a (Hia), e (Hie), and f (Hif) strains by comparison of restriction digest patterns (RDPs). Recent Hia isolates exhibited moderate genetic diversity, with the majority segregating into two major clonotypes. Recent Hie and, especially, Hif strains displayed considerably restricted genetic diversity. In particular, all but one Hif strain segregated into a single clonotype, and half of these isolates had identical RDPs. These results are consistent with the hypothesis that the increased incidence of disease due to non-type b encapsulated H. influenzae reflects the emergence of hypervirulent clones, especially in the case of Hif. Alternatively, it is possible that non-type b encapsulated H. influenzae strains have limited overall genetic diversity.

PMID: 11923343 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11760167&dopt=Abstract

 
Scand J Infect Dis 2001;33(11):848-50 Related Articles, Links
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Changes in serotype distribution may hamper efficacy of pneumococcal conjugate vaccines in children.

Normark BH, Ortqvist A, Kalin M, Olsson-Liljequist B, Hedlund J, Svenson SB, Kallenius G.

Department of Bacteriology, Swedish Institute for Infectious Disease Control, Solna. Birgitta.Henriques@smi.ki.se

During the last 10 y we have observed an increased incidence of pneumococcal bacteremia in Sweden. In order to study the serotype distribution over time we collected 1136 invasive pneumococcal isolates from 1987, 1992 and 1997 from Swedish microbiological laboratories. Currently, new pneumococcal conjugate vaccines are being considered for introduction in the general childhood vaccination program in several countries, including Sweden. We studied the potential vaccine coverage rate for the new conjugate vaccines among our Swedish invasive isolates. We found that the serotype distribution fluctuated with time and observed a surprisingly low potential coverage rate for the 7-valent vaccine in Sweden, in contrast to other countries. Therefore we argue that pneumococcal conjugate vaccines have to be tailored to suit current, local serotype patterns and most likely will need to be changed over time.

PMID: 11760167 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11427408&dopt=Abstract

 
Am J Epidemiol 2001 Jul 1;154(1):85-92 Related Articles, Links
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Interpreting results from trials of pneumococcal conjugate vaccines: a statistical test for detecting vaccine-induced increases in carriage of nonvaccine serotypes.

Lipsitch M.

Department of Biology, Graduate School of Arts and Sciences, Emory University, Atlanta, GA. mlipstic@hsph.harvard.edu

Conjugate vaccines against Streptococcus
pneumoniae (pneumococcus) protect against nasopharyngeal carriage of serotypes included in the vaccine. However, in several clinical trials, vaccinees have shown increased carriage of nonvaccine serotypes of pneumococcus. These increases may be due to serotype replacement, if vaccine-induced protection against carriage of vaccine serotypes increases susceptibility to carriage of nonvaccine serotypes. Alternatively, observed increases may be an artifact of "unmasking," in which nonvaccine serotypes are more readily detected among vaccinees than among controls because vaccine serotypes are not present. In this paper, a statistical test for distinguishing serotype replacement from unmasking is described. The test attempts to reject a null model of unmasking alone; serotype replacement is inferred if the observed increase in detectable nonvaccine serotype carriage among vaccinees is significantly greater than that expected under the null model. Significance is assessed using the Bayesian "posterior predictive p value" as modified by Robins et al. (J Am Stat Assoc 2000;95:1143-56). Analysis of data from a South African trial suggests that replacement may have occurred in the study, but results do not reach the conventional level of significance in rejecting the null hypothesis of unmasking (p = 0.074). The author performs sensitivity analyses for the prior and for unmeasured confounding by differences in susceptibility to pneumococcus carriage. The implications of the findings and the assumptions and limitations of this technique are then discussed.

PMID: 11427408 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11779452&dopt=Abstract

 
Braz J Infect Dis 2001 Oct;5(5):260-8 Related Articles, Links

An epidemiological study of Haemophilus influenzae at a Brazilian day care center.

da Silva ME, Marin JM.

University of Sao Paulo, Ribeirao Preto Campus, Av do Cafe/No. Campus USP, CEP 14040-904, Ribeirao Preto, Sao Paulo, Brazil.

Day care centers are a relatively new phenomenon in Brazil that bring together large numbers of young children susceptible to contagious diseases. Haemophilus influenzae (Hi) is an important infection in the age range of those attending day care centers. In the present study, the carriage rate of Haemophilus influenzae was identified in 38 day care attendees age 6 to 37 months, and 23 staff members, at a day care center in Ribeirao Preto-Sao Paulo, in 1997. To identify the carriers, two nasopharyngeal swabs were collected; one in July and one in December. The rate of H. influenzae carriers among the children was 77%. Only 2 of 23 staff members (9%) had Hi. Among the children, there were 58 isolates in the two sampling periods; 6 of the Hi were serotype b, 1 was serotype e, and 48 isolates were non-typeable. Two were identified as H. parainfluenzae. One adult had a non-typeable Hi and 1 had H. paraphrohaemolyticus. Three of the 6 children with type B had received a conjugate vaccine against H. influenzae type b, but they still carried this bacterium in the nasopharynx (50%). Forty ribotype patterns were found among the isolates, showing a high exchange rate of nontypeable H. influenzae carriers. The results indicate that, because of the high and changing biotype of Hi carriage, day care centers should be carefully monitored as potential point source of HI disease in the community.

PMID: 11779452 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11072934&dopt=Abstract

 
Lancet 2000 Oct 7;356(9237):1210-1 Related Articles, Links
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Prevention of pneumococcal disease by vaccination: does serotype replacement matter?

Spratt BG, Greenwood BM.
 
From the article: "An early study of Gambian infants immunised with a five-valent pneumococcal conjugate vaccine, and then re-immunised with a 23-valen pneumococcal polysaccharide vaccine at the age of 2 years showed a reduction in the prevalence of nasopharyngeal carriage of pneumococci of the vaccine serotypes.  However, replacement with pneumococci of non-vaccine serotypes occurred, so the overall prevalence of pneumococcal carriage in vaccinated children was little changed...In the second Israeli study, which was undertaken in children attending day-care centres, pneumococci of non-vaccine serotypes were found infrequently in very young children and remained uncommon in non-vaccinated children.  However, in vaccinated children, the proportion of pneumococci isolated from the nasopharynx of non-vaccine non-vaccine serotypes, relative to those of vaccine serotypes, increased gradually with age, and by the age of 3 years, pneumococci of non-vaccine serotypes predominated. The results of these carriage studies suggest that replacement of vaccine serotypes by non-vaccine serotype in the nasopharynx will occur after mass implementation of the conjugate pneumococcal vaccine.  Whether this replacement will increase the incidence of invasive disease caused by pneumococci of the latter types is difficult to predict."

Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, Oxford University, UK.

PMID: 11072934 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11163471&dopt=Abstract

 
Vaccine 2000 Dec 8;19 Suppl 1:S96-9 Related Articles, Links
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Acute otitis media in the era of effective pneumococcal conjugate vaccine: will new pathogens emerge?

Pelton SI.

Section of Pediatric Infectious Diseases, Boston Medical Center, Boston University School of Medicine, 774 Albany Street-Suite 512, Boston, MA 02118, USA. spelton@bu.edu

The immunogenicity of pneumococcal conjugate vaccine (PCV) in young infants and its serotype-specific efficacy in otitis media (OM) results in a modest reduction in total episodes of OM and a more substantial reduction in disease due to the most frequent pneumococcal serotypes. Since PCV will only prevent disease due to the most common serotypes, concerns about potential changes in the microbiology of OM have emerged. Insight into potential changes can be obtained from reviewing middle ear and nasopharyngeal isolates from studies of antimicrobial prophylaxis and bacterial polysaccharide immune globulin for prevention of OM and PCV for prevention of invasive pneumococcal disease, respectively. In children receiving PCV, a shift in serotypes of SP colonizing the nasopharynx has been observed. Since non-vaccine serotypes are already present in the community as the etiology of acute purulent OM, it is predictable that these non-vaccine serotypes will become more common especially in children less than two years of age.

Publication Types:
  • Review
  • Review, Tutorial


PMID: 11163471 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11083991&dopt=Abstract

 
An Esp Pediatr 2000 Oct;53(4):369-71 Related Articles, Links
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[Meningitis due to haemophilus influenzae type f]

[Article in Spanish]

Gonzalez Lopez M, del Pino De La Fuente A, Garcia Martin FJ, Calbo Torrecillas F, Obando Santaella I, Campos J, Martinez Valverde A.

Departamento de Pediatria, Hospital Materno Infantil de Malaga, Madrid.

We report an immunocompetent 5-month-old boy with Haemophilus influenzae type f (Hif) meningitis. The patient had previously been immunized with two doses of Hib conjugate vaccine (PRP-T). Vaccination failure was initially suspected based on Gram stain report. The results of culture identified a non-b Haemophilus influenzae capsular serotype (Hif).Non-Hib serotypes should be considered as potential pathogenic agents in children under the age of 5 years with invasive diseases. An adequate epidemiological surveillance system would be helpful in detecting the role of these non-b Hif serotypes as significant pathogens, which appear to be on the increase.

PMID: 11083991 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10812233&dopt=Abstract

 
Vaccine 2000 Jun 15;18(25):2895-901 Related Articles, Links

Erratum in:
  • Vaccine 2000 Oct 15;19(4-5):598

Click here to read 
Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model.

Lipsitch M, Dykes JK, Johnson SE, Ades EW, King J, Briles DE, Carlone GM.

Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. mlipsitc@hsph.harvard.edu [corrected]

Widespread use of conjugate vaccines against Streptococcus pneumoniae, by reducing carriage of S. pneumoniae serotypes included in the vaccine, may result in an increase in nasopharyngeal carriage of - and disease from - nonvaccine serotypes of the same species. Mathematical models predict that the extent of such replacement will depend positively on the degree to which carriage of vaccine-type S. pneumoniae inhibits acquisition of nonvaccine-type pneumococci, and may depend negatively on the inhibition of vaccine-type pneumococci by nonvaccine-type pneumococci. We used a mouse model of intranasal carriage of pneumococci to test whether such inhibition occurs between different pneumococcal strains. Mice carrying a streptomycin-resistant derivative of S. pneumoniae BG9163 (serotype 6B) as a resident strain showed reduced levels of colonization when challenged intranasally by optochin-resistant derivatives of the same strain and of a serotype 23F pneumococcus, BG8826. Inhibition could be overcome by increasing the dose of the challenge strain. Carriage of optochin-resistant BG9163 did not inhibit acquisition of the streptomycin-resistant variant. Colonization by a challenge strain did not significantly affect the level of colonization with the resident strain. These results provide evidence that is consistent with several hitherto untested assumptions of mathematical models of serotype replacement and suggest that a biological mechanism exists that could account for serotype replacement that is observed in clinical trials. The findings provide a basis for further studies of in vivo interactions between strains of S. pneumoniae.

PMID: 10812233 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11062808&dopt=Abstract

 
Med J Aust 2000 Oct 2;173 Suppl:S48-50 Related Articles, Links

Conjugate pneumococcal vaccines: an overview.

Mulholland EK.

Department of Paediatrics, University of Melbourne, VIC. mulhollk@cryptic.rch.unimelb.edu.au

A seven-valent conjugate pneumococcal vaccine has been shown to have dramatic efficacy against invasive pneumococcal disease and lesser efficacy against otitis media and pneumonia. This vaccine was licensed for use in infants in the United States in February 2000 and is recommended there for routine use in infants and catch-up vaccination in high-risk children. Specific regional pneumococcal vaccines are not needed; nine to 11 serotypes cover most pneumococcal disease in most parts of the world; nine- and 11-valent conjugate vaccines are currently being developed for the global market. There is evidence of serotype replacement in vaccine recipients (in both carriage and disease), which might reduce overall vaccine effectiveness. There is also evidence that vaccines may reduce rates of antimicrobial resistance in pneumococci. Studies of the burden of pneumococcal disease as well as program support are needed to assist developing countries to introduce these expensive vaccines.

Publication Types:
  • Review
  • Review, Tutorial


PMID: 11062808 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11137259&dopt=Abstract

 
Vaccine 2000 Dec 8;19(9-10):1211-7 Related Articles, Links
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Confronting the pneumococcus: a target shift or bullet change?

Obaro SK.

Medical Research Council Laboratories, P.O. Box 273, Fajara, Gambia. sobaro@gamtel.gm

Pneumococcal disease remains a major killer, despite several years of biomedical research and vaccine technology. The striking efficacy of a seven-valent pneumococcal conjugate vaccine in the US brings hope for the potential conquest of pneumococcal disease but there are still several obstacles in completing this conquest. Although capsular specific antibodies have been shown to be highly protective, it remains unclear what concentration of these serotype-specific antibodies protect against disease and more recently it has become clear that opsonic activity and avidity of these antibodies are more critical determinants of protection than concentration. During the last decade the immunogenicity and protective capacity of several pneumococcal proteins have been described in animal models and these are now being explored for the development of species-common protein based vaccines. Protein conjugate vaccines are no doubt a great new addition to our amarmatorium in the battle against pneumococcal disease but for several epidemiologic reasons the results from Northern California will not be applicable to most other parts of the world. The vaccine contains a limited number of pneumococcal serotypes and given adequate ecological pressure, replacement disease by non-vaccine serotypes remains a real threat, particularly in areas with very high disease burden. The development of new non-serotype-specific vaccine candidates should be encouraged. Defining immune correlates of protection is crucial for the evaluation of these new generation vaccines. As currently available diagnostic methods are poorly sensitive, the true burden of pneumococcal disease may not be revealed until there is a highly efficacious vaccine in widespread use.

Publication Types:
  • Review
  • Review, Tutorial


PMID: 11137259 [PubMed - indexed for MEDLINE]


Record 54 of 210 in SilverPlatter MEDLINE(R) (1999-2001)
TI: Prevention of pneumococcal disease by vaccination: does serotype replacement matter?
AU: Spratt,-B-G; Greenwood,-B-M
SO: Lancet. 2000 Oct 7; 356(9237): 1210-1.
JN: Lancet-;
IS: 0140-6736
LA: English
RO: National-Library-of-Medicine
AN: 20523086
View Complete Record
 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10982068&dopt=Abstract

 
Epidemiol Infect 2000 Jun;124(3):441-7 Related Articles, Links

Invasive Haemophilus influenzae disease in adults.

Sarangi J, Cartwright K, Stuart J, Brookes S, Morris R, Slack M.

Public Health Laboratory, Gloucestershire Royal Hospital, UK.

We reviewed retrospectively all invasive Haemophilus influenzae (Hi) infections in adults ascertained from reference laboratory records and notifications from five NHS regions over the 5 years from 1 October 1990, a period encompassing the introduction of routine Hib childhood immunization (October 1992). A total of 446 cases were identified, a rate of 0.73 infections per 10(5) adults per annum. Though numbers of Hib infections in adults fell after the introduction of Hib vaccines for children (P = 0.035), and there was no increase in infections caused by other capsulated Hi serotypes, total numbers of invasive Hi infections increased due to a large rise in infections caused by non-capsulated Hi (ncHi) strains (P = 0.0067). There was an unexpectedly low rate of infections in those aged 75 years or more (P < 0.0001). The commonest clinical presentations were pneumonia with bacteraemia (227/350, 65%) and bacteraemia alone (62/350, 18%) and the highest rates of disease were in the 65-74 years age group (P < 0.0001). Clinical presentation was not influenced by the capsulation status of the invading Hi strain. 103/350 cases (29%) died within 1 month, and 207/350 (59%) within 6 months of their Hi infection. Case fatality rates were high in all age groups. Pre-existing diseases were noted in 220/350 cases and were associated with a higher case fatality rate (82% vs. 21%, P < 0.0001). After the introduction of Hib immunization in children, invasive Hib infections in unimmunized adults also declined, but the overall rate of invasive Hi disease in adults increased, with most infections now caused by non-capsulated strains. Physicians and microbiologists should be aware of the changing epidemiology, the high associated mortality and high risk of underlying disease. Invasive haemophilus infections in adults should be investigated and treated aggressively.

PMID: 10982068 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10451007&dopt=Abstract

 
Am J Med 1999 Jul 26;107(1A):34S-43S Related Articles, Links

Bacteremic pneumococcal pneumonia in one American City: a 20-year longitudinal study, 1978-1997.

Mufson MA, Stanek RJ.

Department of Medicine, Marshall University School of Medicine, Huntington, West Virginia 25701-3655, USA.

A surveillance of bacteremic pneumococcal pneumonia was conducted in Huntington, West Virginia, from 1978 to 1997 to investigate case-fatality rates, incidence of disease, capsular types, and antibiotic usage. Our study population comprised consecutive inpatients admitted to the hospitals in Huntington, West Virginia, and included 45 children younger than 15 years and 328 adults. All blood isolates were serotyped by capsular swelling procedures; clinical characteristics, treatment, and outcome for all patients were abstracted from hospital charts. The overall case-fatality rate was 20.3%, with most deaths occurring among adults older than 50 years. Case-fatality rates peaked at 37.7% among patients 80 years of age and older. Only 1 of 45 (2.2%) children died. Case-fatality rates declined in each successive 5-year period, from 30.2% in 1978-1982 to 15.6% in 1993-1997. In that same period, incidence rates increased severalfold among children younger than 4 years to 44.5 cases per 100,000 population and among adults 70 years and 80 years of age and older to 38.5 and 76.2 cases per 100,000, respectively. Of the 34 serotypes isolated, 10 accounted for two thirds of the cases of pneumonia: 1, 4, 9, 14, 3, 6, 12, 5, 23, and 19 (in rank order). Chronic renal disease and arteriosclerotic heart disease increased the risk of death. Treatment regimens that included a macrolide and a penicillin or cephalosporin resulted in the lowest case-fatality rate in adults older than 50 years: 6% in 1993-1997. In conclusion, as bacteremic pneumococcal pneumonia evolved over time, the case-fatality rate decreased, its incidence increased, predominant capsular types changed, and treatment regimens that included a macrolide resulted in the lowest fatality rates.

PMID: 10451007 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10341170&dopt=Abstract

 
Emerg Infect Dis 1999 May-Jun;5(3):336-45 Related Articles, Links

Erratum in:
  • Emerg Infect Dis 1999 Sep-Oct;5(5):734

Click here to read 
Bacterial vaccines and serotype replacement: lessons from Haemophilus influenzae and prospects for Streptococcus pneumoniae.

Lipsitch M.

Emory University, Atlanta, Georgia, USA. lipsitch@epinet.harvard.edu

Conjugate vaccines have reduced the incidence of invasive disease caused by Haemophilus influenzae, type b (Hib), in industrialized countries and may be highly effective against Streptococcus pneumoniae. However, the serotype specificity of these vaccines has led to concern that their use may increase carriage of and disease from serotypes not included in the vaccine. Replacement has not occurred with the use of Hib vaccines but has occurred in trials of pneumococcal vaccines. Mathematical models can be used to elucidate these contrasting outcomes, predict the conditions under which serotype replacement is likely, interpret the results of conjugate vaccine trials, design trials that will better detect serotype replacement (if it occurs), and suggest factors to consider in choosing the serotype composition of vaccines.

PMID: 10341170 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9466257&dopt=Abstract

 
Mol Microbiol 1998 Jan;27(1):73-83 Related Articles, Links
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Recombinational exchanges at the capsular polysaccharide biosynthetic locus lead to frequent serotype changes among natural isolates of Streptococcus pneumoniae.

Coffey TJ, Enright MC, Daniels M, Morona JK, Morona R, Hryniewicz W, Paton JC, Spratt BG.

Molecular Microbiology Group, School of Biological Sciences, University of Sussex, Brighton, UK.

Serotype 19F variants of the major Spanish multiresistant serotype 23F clone of Streptococcus pneumoniae have been proposed to have arisen by recombinational exchanges at the capsular biosynthetic locus. Members of the Spanish multiresistant serotype 23F clone and the serotype 19F variants were confirmed to be essentially identical in overall genotype, as they were indistinguishable by REP-PCR, and had identical sequences at three polymorphic housekeeping genes. Eight serotype 19F variants were studied and all had large recombinational replacements at the capsular biosynthetic locus. In all cases, one of the recombinational cross-over points appeared to be upstream of dexB, which flanks one end of the capsular locus, and in six of the variants the other cross-over point was downstream of aliA, which flanks the other end of the locus. In two strains a recombinational cross-over point between the introduced serotype 19F capsular region and that of the Spanish serotype 23F clone could be clearly identified, within cpsN in one strain and within cpsM in the other. The differences in the recombinational junctions and sequence polymorphisms within the introduced capsular genes, suggested that the eight serotype 19F variants emerged on at least four separate occasions. Changes in capsular type by recombination may therefore be relatively frequent in pneumococci and this has implications for the long-term efficacy of conjugate pneumococcal vaccines that will protect against only a limited number of serotypes.

PMID: 9466257 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9918989&dopt=Abstract

 
Enferm Infecc Microbiol Clin 1998 Dec;16(10):449-52 Related Articles, Links

[Bacterial meningitis in the health sector of Virgen del Rocio, Spain]

[Article in Spanish]

Fernandez-Lopez M, Martinez-Hornos M, Navarro J, Cintado C.

Seccion de Infectologia, Hospital Universitario Infantil Virgen del Rocio, Sevilla.

BACKGROUND: The aim of this study was review the epidemiology of the bacterial meningitis in our area. MATERIAL AND METHODS: A retrospective study was carried out of all the cases of bacterial meningitis in children with ages between two months and fourteen years, admitted in our hospital between 1986 and 1997. The following variables we analyzed: Sex, age of the patient, yearly and monthly incidence, previous antibiotic therapy, length of hospital stay, and analytical data of blood and cerebrospinal fluid. RESULTS: In the 755 cases analyzed, the 50% correspond to bacterial meningitis, the 47.6% to viral or aseptic and 2.3% to tuberculous. In of the bacterial meningitis Neisseria meningitidis was isolated in 55.7% of cases, Haemophilus influenzae in 20.4%, Streptococcus pneumoniae in 5.5%, other bacterias in 3.4%, and in 14.5% was not isolated any bacteria. We are assisting to an increase of Neisseria meningitidis serotype C during the last years. Haemophilus influenzae represents a more percentage of bacterial meningitis that in prior years. In meningitis by Streptococcus pneumoniae we observe a clear association with risk factors in children older than 2 years. CONCLUSION: Neisseria meningitidis is the main etiologic agent in children. The vaccination against Haemophilus influenzae serotype b and Neisseria meningitidis A and C can change the epidemiology in next years.

PMID: 9918989 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9568952&dopt=Abstract

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

PMID: 9568952 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9127510&dopt=Abstract

 
Commun Dis Rep CDR Rev 1997 Apr 4;7(4):R49-54 Related Articles, Links

Changing patterns of case ascertainment and trends in meningococcal disease in England and Wales.

Ramsay M, Kaczmarski E, Rush M, Mallard R, Farrington P, White J.

Immunisation Division PHLS Communicable Disease Surveillance Centre, London. mramsay@phls.co.uk

We have reviewed data on meningococcal disease routinely collected in England and Wales from 1989 to 1995 to illustrate and explain changing patterns and guide future surveillance. Statutory notifications of meningococcal meningitis and septicaemia, laboratory confirmed infections, and death registrations coded as meningococcal disease were analysed in terms of their numbers, the age of cases, season of the report, and (if available) site of isolation, serogroup, and serotype. Case fatality rates were estimated for clinically diagnosed and culture confirmed cases. The number of cases notified each year, in particular those notified as septicaemia, rose significantly over the period (p < 0.0001) but there was no net change in the number of culture confirmed cases. Case fatality rates estimated from routine data fell, most markedly for cases notified as septicaemia, but the true case fatality rate of culture confirmed cases did not change between 1993 and 1995. These data suggest that reporting practice changed between 1989 and 1995 and that the ascertainment of clinically diagnosed disease improved, particularly for meningococcal septicaemia. Late in 1995, reports from all data sources increased and the age distribution of both notified and laboratory confirmed cases changed. These changes were accompanied by an increase in the proportion of infections due to Neisseria meningitidis of serogroup C and a significant increase in serotype C2a infections (p < 0.0001). Continuing efforts to reconcile data from several sources will be needed to ensure that routine data can be interpreted accurately to provide evidence for the development of future vaccination policy and to monitor vaccination programmes. In addition, the role of non-culture diagnosis will be crucial in enhancing surveillance based on clinical diagnoses.

PMID: 9127510 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9177259&dopt=Abstract

 
Proc Natl Acad Sci U S A 1997 Jun 10;94(12):6571-6 Related Articles, Links
Click here to read 
Vaccination against colonizing bacteria with multiple serotypes.

Lipsitch M.

Department of Biology, Emory University, Atlanta, GA 30322, USA.

Conjugate vaccines protect vaccinated individuals against both disease from and nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae. Protection is specific to the capsular serotype(s) included in the vaccine. This specificity has raised concern that vaccination against particular ("targeted") serotypes may cause an increase in carriage of (and diseases attributable to) nontargeted serotypes. I analyzed a mathematical model designed to predict the factors affecting, and the expected extent of, such replacement in the host population. The conditions for competitive exclusion and coexistence of serotypes under mass vaccination are derived, and the equilibrium carriage of target and nontarget serotypes is determined under various ecological and epidemiological conditions. The eradication threshold for a target serotype in the presence of competing, nontarget serotypes is always lower for serotype-specific than for bivalent vaccines. In a two-serotype model, the increase in the prevalence of any single nontargeted serotype due to vaccination will not exceed the total reduction in prevalence of a targeted serotype. However, if three or more serotypes interact epidemiologically, vaccination against one type may increase carriage of a second more than it decreases carriage of the first. Carriage of a second serotype against which the vaccine offers only partial protection may initially increase and then decrease as a function of vaccine coverage. I discuss the extent to which these theoretical results can account for existing data on serotype replacement after vaccination against H. influenzae and their implications for vaccine policy.

PMID: 9177259 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8783712&dopt=Abstract

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

Comment in:


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-Robinson 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.

PMID: 8783712 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8589168&dopt=Abstract

 
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.

PMID: 8589168 [PubMed - indexed for MEDLINE]

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