Download Reduced incidence of septic arthritis in children by Haemophilus

Reduced incidence of septic arthritis in
children by Haemophilus influenzae type-b
vaccination
IMPLICATIONS FOR TREATMENT
Heikki Peltola, Markku J. T. Kallio, Leila Unkila-Kallio
From the University of Helsinki, Finland
n many countries Haemophilus influenzae type b
(Hib) is the second most common cause of septic
arthritis in children. In Finland large-scale
immunisation against Hib using conjugate vaccines
began in 1986, four years after a multicentre
prospective study of orthopaedic infections in children
had started.
Since 1982, including six years before and ten after
starting routine Hib vaccination, there has been a
major change in the pattern of septic arthritis. From
1982 to 1988, 32 of 61 cases (53%) were caused by
staphylococci, 22 (36%) by Hib and 7 (11%) by other
bacteria. Since 1988, Hib infection has disappeared,
and one-third of cases of childhood septic arthritis has
been eliminated. This change has allowed us to reduce
initial antimicrobial therapy for such children to cover
only Gram-positive cocci. The more limited treatment
is safer, reduces cost, and simplifies treatment.
I
J Bone Joint Surg [Br] 1998;80-B:471-3.
Received 19 August 1997; Accepted after revision 10 December 1997
Septic arthritis of childhood is a serious complication of
bacteraemia. Before antimicrobial agents were available the
1
mortality could exceed 50% and severe late physical
handicap was common. Deaths are now rare, but still
2
occur, and complications develop in 10% to 50% of
3,4
cases. Staphylococcus aureus is the commonest cause
with Haemophilus influenzae type b (Hib) the next common
after the neonatal period, particularly from three months to
2,5-8
three years of age
In Finland, septic arthritis accounted
for almost 25% of all Hib disease except meningitis and
9
10
8
epiglottitis; in Argentina and Paraguay the proportion
was 10% and 5%, respectively.
H. Peltola, Professor
M. J. T. Kallio, MD, Senior House Officer
Helsinki University Central Hospital, Hospital for Children and Adolescents, 11 Stenbäck Street, FIN-00290 Helsinki, Finland.
L. Unkila-Kallio, MD, Senior House Officer
Departments I and II of Obstetrics and Gynaecology, University of
Helsinki, Helsinki, Finland.
Correspondence should be sent to Professor H. Peltola.
©1998 British Editorial Society of Bone and Joint Surgery
0301-620X/98/38296 $2.00
VOL. 80-B, NO. 3, MAY 1998
Before vaccination for Hib was introduced in Finland,
the incidence of Hib arthritis from birth to 4 years was 4.9
11
per 100 000 per year and 7 per 100 000 in non-Aboriginal
12
children in Australia; in Aboriginals it was 33 per
100 000. A worldwide incidence of 6 per 100 000 is probably a conservative estimate, since such infections are more
common in developing countries; this implies that there are
13
about 40 000 cases per year in the 631 million children in
this age range.
Finland has the longest experience of the use of Hib
conjugate vaccines in Europe, since large-scale vaccination
started in 1986. It was considered that vaccination would
probably change the epidemiology and hence the management of septic arthritis in children.
Patients and Methods
In 1982, we began a prospective study on acute joint
inflammation in children in eight hospitals in Finland, using
a protocol approved by their ethical committees. We included all children between three months and 15 years of age,
in whom septic arthritis was suspected because of pain,
limitation of joint movement, often visible joint swelling,
and fever. We carefully recorded bacteriological documentation of the aetiology: local specimens and blood
cultures were mandatory. A positive culture from a joint
was taken as diagnostic, but a positive blood culture was
accepted only if there were symptoms and signs of septic
arthritis.
Routine investigations included measurement of the ESR
14
(8 times) and serum C-reactive protein levels (12 times
15
from finger-tip specimens ) and radiography (4 times).
Special follow-up forms were completed and all patients
were followed up for at least 12 months.
The final analysis included only cases with full bacteriological documentation and was performed at the Helsinki
University Central Hospital, Hospital for Children and
Adolescents.
Vaccination. In Finland the first Hib conjugate, diphtheria
16
toxoid conjugate (PRP-D), became available in 1986 and
17,18
was tested in the field from 1986 to 1989.
During the
first two years, 50% of infants were offered PRP-D at the
age of 3, 4 and 6 months, with a booster dose at 14 to 18
months. The other 50% received one dose of PRP-D and
471
472
H. PELTOLA,
M. J. T. KALLIO,
L. UNKILA-KALLIO
Fig. 1
Histogram showing all cases of septic arthritis in children in eight hospitals in Finland. Hib vaccination
eliminated one-third within three years of its introduction, with no Hib cases after 1988, but no other change in
the aetiological spectrum. The dotted line shows the two years (1986-7) when vaccination was offered to only
50% of infants (GAS, haemolytic group-A streptococci).
the group-A plus C meningococcal polysaccharide vaccine
at the age of 24 months.
19
Since 1988, mutant diphtheria toxoid conjugate (PRP20
CRM, HbOC) and tetanus toxoid conjugate (PRP-T) have
also been used. First, PRP-D was challenged by PRP-CRM
18
in a randomised efficacy trial in 1988-9, then PRP-T
alone was used in 1990-3 and changed back to PRP-CRM
in 1994. From 1988, only two primary doses have been
administered at the age of four and six months, with a
booster dose at 14 to 18 months. These vaccinations are
performed routinely by public-health nurses working in
1000 child-health centres under the supervision of local
physicians. All vaccinations are free of charge, and volun17
tary vaccination coverage exceeds 95%.
Results
Between 1982 and 1988, there were 61 cases of septic
arthritis (Fig. 1); 32 (53%) were caused by staphylococci,
22 (36%) by Hib, 3 (5%) by Streptococcus pyogenes, 2
(3%) by pneumococci and 2 (3%) by meningococci.
In 1989 three years after the beginning of vaccination,
there was a dramatic change in aetiology: Hib was no
longer a causative agent (Fig. 1). There was no other
change in incidence or distribution. Between 1989 and
1997, there were 46 cases of septic arthritis: 34 (74%) were
caused by Staphylococcus aureus, 7 (15%) by Streptococcus pyogenes and 5 (11%) by pneumococci. Not one
case of Hib arthritis has been reported from anywhere in
Finland.
This change has allowed us to modify our antimicrobial
therapy. Unless there are special reasons to consider
another aetiology, suspected septic arthritis is treated with
only clindamycin or a first-generation cephalosporin such
as intravenous cephalothin, oral cefadroxil or oral cephalexin. On rare occasions an effective penicillin such as
flucloxacillin may be given. These antibiotics effectively
cover Staph. aureus and streptococci, which are now virtually the only bacteria causing septic arthritis from birth to
four years. This treatment policy has worked well, with no
reports of failures of treatment or late sequelae.
Discussion
The role of Hib in septic arthritis has been recognised only
5,7
during a few decades,
probably because the culture
requirements of Hib delayed its recognition until chocolate
agar became widely used.
Before Hib vaccination about 36% of cases of septic
arthritis in Finland were due to this organism. After Hib
vaccination, this cause has disappeared and the incidence of
21
22
23
Hib meningitis, epiglottitis, and other Hib diseases
has declined. This decrease occurred within three years of
the introduction of PRP-D, although it is the conjugate with
24
the least immunogenic potential, and for two years it was
17
offered to only 50% of infants (Fig. 1).
Since 1988, vaccinations used three different conju23
gates, and have been given to practically all infants. This
appears to have eliminated Hib from the aetiology of septic
arthritis in this country, in part by reducing nasopharyngeal
25
carriage. This effect of vaccination has not been associated with any increase in the absolute numbers of other
types of infection. This is in contrast to the area around
Kansas City in the USA, where the overall incidence of
joint infection in children, mainly due to staphylococci and
streptococci, seems to have increased in the past few
26
years.
The change in the epidemiology has had clear implicaTHE JOURNAL OF BONE AND JOINT SURGERY
SEPTIC ARTHRITIS IN CHILDREN REDUCED BY HAEMOPHILUS INFLUENZAE TYPE-B VACCINATION
tions for therapy. In Africa and some other areas Salmonella species and other Gram-negative bacteria are
27
common, but in Finland Gram-positive cocci are now the
only relevant bacteria causing septic arthritis in children.
For this reason, clindamycin and first-generation cephalosporins give adequate microbiological cover and also
penetrate joints and bones very well. Narrowing of the
antibacterial spectrum has simplified treatment, reduced
cost, and exposed patients to fewer allergic and other
adverse reactions.
We thank the following colleagues for their long and excellent contribution in the participating hospitals: Kari Aalto, Ilkka Anttolainen, Riitta
Fagerholm, Hannu Haavisto, Marja Heikkinen, Anita Hiippala, Pentti
Kallio, Ulla Kaski, Juhani Merikanto and Pekka Ojajärvi. We also thank
Sini Kangas, MBA, for her contribution to the writing of the
manuscript.
No benefits in any form have been received or will be received from a
commercial party related directly or indirectly to the subject of this
article.
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