Successful vaccines exist for type b
(but not nontypeable)
Haemophilusinfluenzae
and to some (but not all) serotypes of Neisseriameningitidis;
completing the 'set' of vaccines presents a major challenge.
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.
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 Neisseriameningitidisserogroup
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.
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 Listeriamonocytogenes
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
serotypereplacement 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
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.
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 bacteremicpneumococcal
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 bacteremicpneumococcal
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.
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 Haemophilusinfluenzae,
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.
Recombinational exchanges at the capsular polysaccharide
biosynthetic locus lead to frequent serotype changes among natural isolates of
Streptococcus pneumoniae.
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.
[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:
Neisseriameningitidis
is the main etiologic agent in children. The vaccination against Haemophilusinfluenzae
serotype b and Neisseriameningitidis
A and C can change the epidemiology in next years.
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.
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 Neisseriameningitidis
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.
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 Haemophilusinfluenzae.
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.
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
Haemophilusinfluenzae
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.
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 Haemophilusinfluenzae
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.
ALL INFORMATION, DATA, AND
MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION
PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS
OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR
LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND
COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH
YOUR HEALTH CARE PROVIDER.
