Diagnosis of acute haematogenous osteomyelitis and septic arthritis: 20 years experience at the University Children's Hospital Basel

Abstract

To review the diagnostic experience with acute haematogenous osteomyelitis (AHOM) and/or septic arthritis at our institution.
Retrospective review of the medical records of those patients with a bacteriologically and/or radiologically confirmed diagnosis, hospitalised in the University Children's Hospital Basel, Switzerland between January 1980 and July 2000.
90 patients (61% males), 4 weeks to 14 years of age, met the inclusion criteria. Median duration of disease prior to hospitalisation was 3 days (range 0-14); 88% were admitted during the first week after onset of complaints. 81 patients received no antimicrobial therapy prior to hospitalisation and are the subject of this presentation. ESR (1st hour in mm; median 36; range 11-124), CRP (mg/l; median 64; range 0-221) and WBC (x 10(9)/l; median 13; range 5-34) were elevated in 100%, 82% and 58% of patients, respectively. Blood cultures (BC) and/or tissue cultures (TC) were performed in 79 (98%) patients. Overall, bacteria were isolated from 53 patients (65%) with Staph. aureus as the most frequent organism (n = 31; 50%). BC were performed in 67 patients and yielded 35 (52%) positive cultures; TC (n = 47) yielded 27 (57%) isolates. In 34 patients with both BC and TC performed, only 12 (35%) were positive in both tests. Diagnostic findings were observed in 23 (59%) of 39 plain radiographs, 31 (56%) of 55 sonograms, 39 (89%) of 44 99mTc-labeled bone scans and 4 (100%) of 4 MRI. 41 patients with diagnostic radiological findings had consecutive TC yielding 30 (73%) bacteriological isolates. Median duration of hospitalisation was 15 days (range 2-66).
Our data indicate that the diagnostic procedures of choice should be 1) early bone scan or MRI, 2) BC and 3) TC. Of supportive laboratory parameters, ESR and CRP were most valuable in our hands.

Full text

Diagnosis of acute haematogenous
osteomyelitis and septic arthritis:
20 years experience at the
University Children’s Hospital Basel
Jan Bonhoeffer, Beate Haeberle, Urs B. Schaad, Ulrich Heininger
University Children’s Hospital Basel, Switzerland
Osteomyelitis is a serious disease characterised
by an infection of the bone marrow, compacta and
periosteum. Various classifications have been pro-
posed [1]. For clinical decision making differenti-
ation of acute from chronic, haematogenous from
contiguous and unifocal from multifocal osteo-
myelitis is helpful.
The spectrum of causative organisms varies by
age group [2–6]. The most commonly identified
pathogen in children above 5 years of age is Staphy-
lococcus aureus. It is implicated in 50–90 percent of
cases in otherwise healthy children [2, 7–9]. A
broader spectrum of causative organisms is found
particularly in infants, where Streptococci, gram-
negative bacteria such as H. influenzae and E. coli are
responsible for up to 60 percent of cases [3, 10–12].
In about one third of cases no causative organism
can be isolated [11, 13–15]. It was proposed that fas-
tidious organisms like Kingella kingae might be re-
sponsible for a considerable proportion of osteo-
myelitis cases with negative routine cultures [16].
The present study focuses on acute haema-
togenous osteomyelitis (AHOM) and septic arthri-
tis, the most common presentation of osteomye-
litis in childhood. Due to slow blood flow in the
capillary bed of ossifying tissue, bacteraemia can
lead to migration of bacteria through the capillary
endothelium and cause secondary local infection.
Commonly a single focus in a metaphyseal area of
long bones is affected. Due to the vascular anatomy
Objective: To review the diagnostic experience
with acute haematogenous osteomyelitis (AHOM)
and/ or septic arthritis at our institution.
Methods: Retrospective review of the medical
records of those patients with a bacteriologically
and/or radiologically confirmed diagnosis, hospi-
talised in the University Children’s Hospital
Basel, Switzerland between January 1980 and July
2000.
Results: 90 patients (61% males), 4 weeks to 14
years of age, met the inclusion criteria. Median du-
ration of disease prior to hospitalisation was 3 days
(range 0–14); 88% were admitted during the first
week after onset of complaints. 81 patients re-
ceived no antimicrobial therapy prior to hospital-
isation and are the subject of this presentation.
ESR (1
st
hour in mm; median 36; range 11–124),
CRP (mg/l; median 64; range 0–221) and WBC
(10
9
/l; median 13; range 5–34) were elevated
in 100%, 82% and 58% of patients, respectively.
Blood cultures (BC) and/or tissue cultures (TC)
were performed in 79 (98%) patients. Overall, bac-
teria were isolated from 53 patients (65%) with
Staph. aureus as the most frequent organism (n =
31; 50%). BC were performed in 67 patients and
yielded 35 (52%) positive cultures; TC (n = 47)
yielded 27 (57%) isolates. In 34 patients with
both BC and TC performed, only 12 (35%) were
positive in both tests. Diagnostic findings were
observed in 23 (59%) of 39 plain radiographs,
31 (56%) of 55 sonograms, 39 (89%) of 44
99m
Tc -
labeled bone scans and 4 (100%) of 4 MRI. 41 pa-
tients with diagnostic radiological findings had
consecutive TC yielding 30 (73%) bacteriological
isolates. Median duration of hospitalisation was
15 days (range 2–66).
Conclusion: Our data indicate that the diagnos-
tic procedures of choice should be 1) early bone
scan or MRI, 2) BC and 3) TC. Of supportive lab-
oratory parameters, ESR and CRP were most valu-
able in our hands.
Key words: acute osteomyelitis; septic arthritis; children;
organism; diagnosis
575
Original article
SWISS MED WKLY 2001;131:575–581 · www.smw.ch
Peer reviewed article
Summary
Introduction

infants are particularly prone to develop concomi-
tant septic arthritis.
Since the introduction of antibiotics and mod-
ern diagnostic techniques, AHOM can be treated
conservatively with good prognosis – provided di-
agnosis is made early [4, 17]. Unless the hip joint
is involved and/or diagnosis is delayed, septic
arthritis can be treated without surgery as well [17].
Various diagnostic approaches have been discussed
in the recent literature [3, 12, 15, 18, 19]. Here
we present the diagnostic experience made during
20 years in our institution.
Diagnosis of acute haematogenous osteomyelitis and septic arthritis: 20 years experience at the University Children’s Hospital Basel
576
Methods
Patients were identified in our medical record regis-
ter by ICD code of discharge diagnosis between January
1980 and July 2000.
Based on the diagnostic criteria for osteomyelitis pro-
posed by Waldvogel et al. [18] we included all patients ful-
filling the following criteria:
1. suspicious and/or characteristic clinical signs and symp-
toms of bone and/or joint infection of <2 weeks duration
and/or
2. positive blood or tissue culture
and/or
3. typical radiological findings (deep soft-tissue swelling,
and/or periosteal reaction, and/or bony destruction) at
some stage during hospitalisation
and/or
4. surgical finding of pus in bone and/or joint
The following data were collected from medical
records of each patient who met the inclusion criteria: date
of birth, gender, date of admission, history of presenting
complaint, other symptoms present, risk factors, clinical
signs, current medication, laboratory, radiological, bacte-
riological and histopathological findings, type and dura-
tion of antimicrobial therapy, any interventions and com-
plications, discharge diagnosis and outcome.
ESR ≥ 10 mm in the first hour, CRP ≥ 20 mg/l and
WBC ≥ 12  10
9
/l were considered abnormal. Blood cul-
tures (BC) typically consisted of one sample pair on ad-
mission. Specimens for tissue cultures (TC) were obtained
by aspiration or open surgical procedure. Radiological
findings were considered “characteristic” according to the
radiology report. Osteomyelitis was considered “acute” if
the history of complaint was shorter than 2 weeks and con-
sidered “haematogenous” in origin in the absence of pen-
etrating wounds adjacent to the site of disease. Arthritis
was considered “septic” if blood and/or or tissue cultures
were positive. According to our inclusion criteria and def-
initions, patients were classified into three diagnostic
groups, irrespective of the discharge diagnosis: AHOM,
septic arthritis and AHOM with septic arthritis.
Results
Study population
A summary of the study population is shown in
figure 1. Data of 81 patients (50 males = 61%) were
available. Median age was 4 years in the septic
arthritis group and 9 years in both the AHOM and
the AHOM with septic arthritis group. Overall 50%
of cases occurred until the age of 6 years (range 0–14
years); 6 cases occurred in the neonatal period. Age
distribution is demonstrated in figure 2. 46 (57%)
of patients were diagnosed as acute haematogenous
osteomyelitis (AHOM) with or without concomi-
tant effusion in the adjacent joint. 23 (28%) were di-
agnosed as septic arthritis and 12 (15%) as AHOM
with septic arthritis. Median duration of complaints
Reasons for Exclusion
Cases identified by ICD code
(n=143)
History of >2 weeks (n=23)
Unconfirmed clinical diagnostic criteria (n=18)
Penetrating wound (n=12)
Inclusion criteria fulfilled
(n=90)
Antibiotic treatment prior to admission (n=9)
Cases for analysis
(n=81)
Figure 1
Study population.

prior to hospitalisation was 3 days (range 0–14 days).
88% were admitted during the first week of com-
plaints. Median duration of hospitalisation was 15
days (range 2–66 days). It varied between patients
with AHOM (14 days), septic arthritis (16 days) and
AHOM with septic arthritis (26 days). The time to
admission as well as the duration of hospitalisation
were independent of the causative organism and pa-
tient age (data not shown).
Clinical presentation
On admission 77 (95%) of 81 patients presented
with pain, 65 (80%) with fever, 61 (75%) with local
signs and 49 (60%) with restricted joint motility. All
four symptoms were present in 32 (39%) patients. In
two infants poor feeding was the main presenting
symptom. In the majority of patients (77%) the loca-
tion of the process was in the lower extremity. In pa-
tients with AHOM the following bones were in-
volved: femur 24%, tibia18%, foot 10%, pelvis 13%,
humerus 5%, clavicle and hand 3%, radius, patella
and fibula and spine 2% each. Multifocal involvement
was found in 13% of patients (6 months to 14 years of
age).
In patients with septic arthritis the following
joints were involved: hip 38%, knee 30%, ankle
18%, elbow 10% and shoulder 4%.
The following results are presented summaris-
ing patients with AHOM and/or septic arthritis.
When analysed separately, no significant differ-
ences were found between groups (data not shown).
Imaging
In 79 patients (97%) radiological imaging
techniques were used. Overall diagnostic radio-
logical findings on admission were observed in 69
(85%) of these patients. 23 (59%) of 39 plain radio-
graphs, 31 (56%) of 55 sonograms, 39 (89%) of
44 (
99m
Tc)-labeled bone scans and 4 (100%) of 4
MRI were consistent with the suspected diagnosis.
During the first week after onset of symptoms,
however, only 42% of radiographs were diagnos-
tic as compared to 87% of bone scans.
Laboratory findings
At the time of admission ESR was performed
in 39 (48%), CRP in 49 (60%) and WBC in 77
(95%) of patients. ESR (1
st
hour in mm; median
36; range 11–124), CRP (mg/l; median 64; range
0–221) and WBC ( 10
9
/l; median 13; range 5–34)
were above normal limits in 100%, 82% and 58%
of patients, respectively. The level of laboratory
parameters did not correlate with duration of his-
tory before hospitalisation (data not shown). A de-
tailed distribution of laboratory results is depicted
in figure 3a–c.
SWISS MED WKLY 2001;131:575–581 · www.smw.ch
577
0
2
4
6
8
0123456789101112131415
Age
N
AHOM
SA
AHOM+SA
Figure 2
Age distribution of
81 patients with acute
hematogenous
osteomyelitis and/or
septic arthritis.
Investigation performance positive cultures
Blood cultures (BC)
or tissue cultures (TC) 79 (98%) 53 (65%)
BC 67 (83%) 35 (52%)
TC 47 (58%) 27 (57%)
Table 1
Results of bacterial
culture in 81 patients
with acute haemato-
genous osteomyelitis
and/or septic
arthritis.
Organism 0–4 years 5–9 years 10–14 years total
(n = 28) (n = 18) (n = 16) (n = 62)
Staphylococcus sp. 14 (50%) 11 (61%) 14 (88%) 39 (63%)
Staph. aureus 8 (28%) 9 (50%) 14 (88%) 31 (50%)
coagulase-negative 6 (21%) 2 (11%) 0 8 (13%)
Streptococcus sp. 8 (29%) 4 (22%) 2 (12%) 14 (23%)
S. pyogenes 3 (11%) 4 (22%) 2 (12%) 9 (15%)
S. pneumoniae 3 (11%) 0 0 3 (5%)
S. agalacticae 2 (7%) 0 0 2 (3%)
H. influenzae 4 (14%) 0 0 4 (6%)
Others 2 (7%) 3 (16%) 0 5 (8%)
Table 2
Prevalence of isolat-
ed organisms by age
of patients with acute
haematogenous
osteomyelitis and/or
septic arthritis.

Diagnosis of acute haematogenous osteomyelitis and septic arthritis: 20 years experience at the University Children’s Hospital Basel
578
ESR on day of admission (n=39)
0
10
20
30
40
<
1
0
1
0
-2
0
2
0
-4
0
4
0
-
6
0
6
0
-8
0
8
0
-
1
0
0
1
0
0
-
1
2
0
[mm/h
]
%
ESR
CRP on day of admission (n=49)
0
10
20
30
40
<
1
0
1
0
-
2
0
2
0
-
5
0
5
0
-
1
0
0
1
0
0
-
1
5
0
1
5
0
-
2
0
0
2
0
0
-
2
5
0
[mg/l]
%
CRP
WBC on day of admission (n=77)
0
10
20
30
40
50
<12
12-14
15-19
20-25
25-30
30-35
[x10
-9
/l]
%
WBC
Figure 3a–c
Distribution of
laboratory results in
patients with acute
hematogenous
osteomyelitis and/or
septic arthritis.
3a: ESR levels
3b: CRP levels
3c: white blood count
a
b
c
Bacteriology
Blood cultures (BC) and/or tissue cultures
(TC) were performed in 79 (98%) of 81 patients.
Overall, bacteria were isolated from 53 patients
(65%). BC were performed in 67 patients (83%)
and yielded 35 (52%) positive cultures. A fine nee-
dle aspirate was performed in 40 (49%), biopsies in
8 (10%) of patients. One aspirate was a punctio sicca.
47 samples yielded pus, infected tissue or joint fluid.
Bacteriological cultures yielded 27 (57%) isolates.
In 34 patients with both BC and TC per-
formed, 12 (35%) were positive in both tests. In 7
(20%) instances only BC and in 7 (20%) only TC
were positive. Bacterial cultures were negative in 8
(23%) patients. The spectrum of organisms iden-
tified was similar in blood and tissue cultures (data
not shown). A total of 62 organisms was detected.
In 8 patients more than one organism could be
identified. There were 39 (63%) Staphylococci (31
S. aureus, 8 coagulase-negative S.), 14 (23%) Strep-
tococci ( 9 S. pyogenes, 2 S. agalacticae, 3 S. pneumo-
niae), 4 (6%) Haemophilus influenzae, and 5 other
bacteria (2 Enterococcus faecalis, 1 Corynebacterium
sp., 1 Actinomyces sp., 1 Propionibacterium sp.). The
prevalence of isolated organisms by patient age is
shown in table 2. Of the 8 cultures (from 8 pa-
tients) yielding coagulase negative Staphylococci,
4 derived from BC and 4 from TC. In the corre-
[x10
–9
/l]

SWISS MED WKLY 2001;131:575–581 · www.smw.ch
579
sponding other bacterial cultures of 4 of these pa-
tients, Enterococci, Haemophilus influenzae, Strep-
tococci or Proteus sp. were found. In the remaining
4 patients, corresponding cultures were negative.
The four patients with cultures positive for
Haemophilus influenzae (not typed) were 6 months
and 1, 2 and 4 years of age. All cases occurred before
1992 (the year of introduction of Hib [Haemophilus
influenzae] immunisation in Switzerland).
Therapy and outcome
Initially all patients received parenteral anti-
biotic therapy for 1–3 weeks, followed by oral
administration to be continued after discharge.
Amoxicillin/clavulanic acid was the most common
initial choice (48%). An aminoglycoside was used
in combination in 18% of patients.
40 patients (50%) underwent therapeutic sur-
gery. Lavage and drainage, curettage and drainage
and bone resection and drainage of the site was
performed in 27, 11 and 3 patients respectively.
On discharge, 38 patients were free of signs
and symptoms, 12 had minor symptoms (such as
residual pain and fatigue) and in 31 patients re-
stricted motility was still noted. 21 of these 31 pa-
tients had undergone surgery during admission.
Discussion
Our diagnostic criteria used for AHOM and
septic arthritis are similar to those previously sug-
gested [18–21]. In the majority of our patients
(77%) the location of the process was in the lower
extremity. The most frequent sites of AHOM were
femur 24% and tibia18%. Septic arthritis was most
commonly observed in the hip in 38% and the knee
30%. Multifocal involvement was found in 13%.
The distribution of involved sites reported in the lit-
erature are 14–50% for the femur, 19–31% for the
tibia, 14–30% for the hip, 35–45% for the knee and
7–12% for multiple lesions [2, 3, 5, 7, 10, 22–25].
On admission most frequent signs and symp-
toms were pain, fever, local signs of infection and
restricted joint motility, which is in accordance
with previously published case series [2, 3, 20–22].
Although pain and fever are the most frequent
symptoms in most case series, our data demon-
strate the variability of clinical presentation and
emphasise the need for early investigation looking
for objective parameters to confirm the diagnosis.
Prompt diagnosis of acute haematogenous os-
teomyelitis in children is essential as complications
and long term sequelae rise dramatically if the diag-
nosis is not made within 3 days of onset of symptoms
with a subsequent delay in implementing appropri-
ate treatment [7, 16]. Median duration of symptoms
of three days before admission in our study is in ac-
cordance with previous reports [2, 17, 20, 21]. Radio-
graphic imaging constitutes the basis of diagnostic
procedures. Sensitivity of early bone scans was 88%
in our hands and this is in the upper range of previ-
ous results and render them suitable for early diag-
nosis. MRI, which has only recently been introduced
as a valuable tool for diagnosing AHOM and also ap-
pears to be very sensitive (positive in all 4 patients
tested). Numbers are, however, too small yet to make
definitive statements as to the role of MRI. This is
consistent with data by Elgazzar et al. reviewing 13
studies comparing imaging modalities for the as-
sessment of osteomyelitis. A mean sensitivity of 88%
for
99
Tc-bone scans and 92% for MRI was calculated
in this review [27]. Jaramillo et al. reviewed 26 chil-
dren with osteomyelitis and reported a positive pre-
dictive value of 85% for MRI and 83% for bone scans
[28]. Although deep tissue swelling can be appreci-
ated on conventional radiographs as early as 48 hours
after onset of disease, earliest signs of bone destruc-
tion can usually only be demonstrated after 7–21
days. This renders conventional radiographs not
helpful for early diagnosis. Ultrasound is a useful
method to suspect the diagnosis relatively early since
subperiostal exudates can be seen as early as 24 h after
onset of disease [29]. However, interpretation of ul-
trasound findings is highly user and device depend-
ent and relies on the presence of significant exudates
or joint effusion. Hence, its sensitivity is consider-
ably variable. Therefore, MRI or bone scan should
be performed if unifocal involvement is suspected. If
multifocal bone or joint involvement is considered,
a bone scan should be the modality of choice.
Our data confirm initial values of ESR and
CRP to be normal only in a small percentage of pa-
tients whereas WBC is a poor indicator of AHOM
and septic arthritis. In a prospective study of 44
children with osteomyelitis, Unkila-Kallio et al.
demonstrated initial ESR, CRP and WBC values
to be elevated in 92%, 98% and 34% of patients,
respectively [19]. Similar data were shown for sep-
tic arthritis by the same group [30]. In a review of
86 children Dahl et al. reported that ESR was ele-
vated in 96%, CRP in 89% and WBC in 12% [20].
Klein and coworkers reviewed 26 paediatric cases
of septic hip infections. They observed ESR to be
elevated in 95% and emphasised that the WBC was
increasing with age and turned out to be positive
in 73% of their cases [31]. The age dependence of
WBC levels could not be confirmed in our analy-
sis (data not shown). Initial values of CRP in our
series were less helpful for a diagnosis of AHOM
and/or septic arthritis compared to ESR values. We
have no ready explanation for this observation.
The diagnosis of AHOM depends on a high
index of suspicion and is strongly supported by im-
aging techniques but is only secured if bacterial
culture is positive [24, 32]. In our study 52% of BC
and 57% of TC were positive. Reviewing ten case
series providing data on positive BC, a mean of

Diagnosis of acute haematogenous osteomyelitis and septic arthritis: 20 years experience at the University Children’s Hospital Basel
580
46% (range 24–74%) can be found [2, 3, 9, 12, 15,
19–21, 26, 30].The mean value for positive TC in
ten previous studies was 67% (range 45–83%) [2,
3, 12, 15, 19–23, 30]. Performing both, BC and
TC, increased the sensitivity by 20% in compari-
son to BC alone in our hands. Still, in one third of
patients no causative agent could be identified.
This is in line with many other previously reported
case series [5, 11, 13–15]. Thus, there is a need to
further improve microbiological diagnostic proce-
dures. Although Jalava et al. could not demonstrate
an increase of organisms found by the use of PCR
in septic arthritis [33], other reports indicate that
PCR may be promising in this respect [34, 35].
Gram positive organisms are the most com-
mon pathogens causing AHOM and SA. A 50%
occurrence of Staph. aureus as the infective agent
in our series is in accordance with previous results.
Cole et al. found Staph. aureus in 48% in a prospec-
tive study of 76 patients with AHOM in Australia,
Dich et al. reported a Staph. aureus rate 59% in a
review of 163 cases of AHOM during 15 years
(1959–73) in the US, Karwowska el al. found 69%
of isolated organisms to be Staph. aureus in their
review of 128 patients with AHOM between 1984
and 96 in the US [2, 7, 21]. Unkila-Kallio et al.
identified Staph. aureus even in 89% of bacteria in
a prospective study of AHOM in Finland [19]. A
recent study by Caksen et al. reviewing 40 patients
with septic arthritis demonstrates the overall fre-
quency of 50% Staph. aureus in children between
6 months and 14 years of age in Turkey [22]. The
observation of a decrease over time of Staph. au-
reus as the causative agent of AHOM from 55% to
31% as described by Craigen et al. in a retrospec-
tive study of 275 patients in Scotland between 1979
and 1990 is not confirmed by our data [26].
The reason for the variability of Staph. aureus
isolation rates in previous studies is probably due to
the wide range of age distribution in these case se-
ries. The predominance of Staph. aureus as the
causative organism was strikingly age-dependent in
our investigation. Staph. aureus represented only
50% of isolates in children younger than 5 years of
age compared to 60% in those 5–9 years of age and
90% in those 10–14 years of age. Although Dich et
al. and Nelson et al. report highest relative Staph.
aureus incidences between 2 and 10 years of age [2,
15] our findings correlate with those of several other
reports providing age related data on causative
organisms [3, 6, 10–12, 23, 36]. For children with
AHOM Highland et al. reported a 50% occurrence
of Staph. aureus in infants and an 80% occurrence
above 5 years of age [36]. Green et al. [10] empha-
sised the high frequency (63%) of Streptococci in
infants with AHOM whereas Welkon et al. found
82% H. influenzae in infants with septic arthritis
[11]. Nelson et al, in a review of 117 patients with
septic arthritis in the US between 1955 and 1965,
and thus long before introduction of immunisation
against Haemophilus, demonstrated that the major
pathogen in the younger age group was H. influen-
zae (17% of positive cultures). In contrast S. aureus
(37% of positive cultures) was the predominant or-
ganism in the older age group [5]. Thus, the diver-
sity of other organisms found particularly in the
younger age groups emphasises the importance to
aim for identification of the causative pathogen. A
needle biopsy or surgical sampling of infected tissue
provides indispensable information. A direct gram
stain of aspirates sometimes helps to determine the
nature of the organism at the earliest possible occa-
sion. In some instances only the histo-pathological
examination of a bone-biopsy specimen will reveal
the accurate diagnosis [24]. Bone and joint aspirate
should be obtained from every patient with sus-
pected AHOM or septic arthritis particularly if
blood cultures are negative. For septic arthritis this
is mandatory for a favorable outcome. For both,
AHOM and septic arthritis, it not only promotes the
effectiveness of antimicrobial therapy but also in-
creases the probability to identify the causative or-
ganism [5, 12, 15, 21]. This will guide the change to
the safest, specific, narrow-range antibiotic therapy
after the required initial, broad empiric treatment.
In conclusion our data suggest that the diag-
nostic procedures of choice should be early MRI or
bone scan, accompanied by blood culture and tis-
sue culture. Of supportive laboratory parameters,
ESR and CRP were most valuable in our hands.
We gratefully acknowledge B. Demba and G. Rerat
for their generous help in record identification as well as
K. Camenzind for the microfilm documentation. Partic-
ular thanks to K. Ewing for his extensive and enlighten-
ing help with scanning the records and feeding the data
base.
Correspondence:
PD Dr. med. Ulrich Heininger
Dept. of Infectious Disease and Vaccines
University Children’s Hospital
P.O.Box
CH-4005 Basel
e-mail: Ulrich.Heininger@unibas.ch

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