infection with S. aureus, possibly
MRSA. The possibility of MRSA
must be considered when initiating
antimicrobial agents to treat TSS.
Sophie Jamart,* Olivier Denis,*
David De Bels,*
and Jacques Devriendt*
*Université Libre de Bruxelles, Brussels,
1. Furukawa Y, Segawa Y, Masuda K,
Takahashi M, Ootsuka A, Hirai K, et al.
Clinical experience of 3 cases of toxic
shock syndrome caused by methicillin
cephem-resistant Staphylococcus aureus
(MRSA). Kansenshogaku Zasshi. 1986;
2. Meyer RD, Monday SR, Bohach GA,
Schlievert PM. Prolonged course of toxic
shock syndrome associated with methi-
cillin-resistant Staphylococcus aureus
enterotoxins G and I. Int J Infect Dis.
3. Lina G, Piémont Y, Godail-Gamot F, Bes
M, Peter MO, Gauduchon V, et al.
Involvement of Panton-Valentine leuko-
cidin-producing Staphylococcus aureus in
primary skin infections and pneumonia.
Clin Infect Dis. 1999;29:1128–32.
4. Oliveira DC, Tomasz A, de Lencastre H.
Secrets of success of a human pathogen:
molecular evolution of pandemic clones of
methicillin-resistant Staphylococcus aureus.
Lancet Infect Dis. 2002;2:180–9.
5. Kikuchi K, Takahashi N, Piao C, Totsuka
K, Nishida H, Uchiyama T. Molecular epi-
Staphylococcus aureus strains causing
neonatal toxic shock syndrome-like exan-
thematous disease in neonatal and perinatal
wards. J Clin Microbiol. 2003;41:3001–6.
6. Denis O, Deplano A, Nonhoff C, De Ryck
R, de Mendonca R, Rottiers S, et al.
National surveillance of methicillin-resist-
ant Staphylococcus aureus (MRSA) in
Belgian hospitals in 2001 indicates rapid
Antimicrob Agents Chemother. 2004;48:
7. Schmitz FJ, MacKenzie CR, Geisel R,
Wagner S, Idel H, Verhoef J, et al.
Enterotoxin and toxic shock syndrome
toxin-1 production of methicillin resistant
and methicillin sensitive Staphylococcus
aureus strains. Eur J Epidemiol. 1997;13:
8. van der Mee-Marquet N, Lina G, Quentin
R, Yaouanc-Lapalle H, Fievre C, Takahashi
N, et al. Staphylococcal exanthematous dis-
ease in a newborn due to a virulent methi-
cillin-resistant Staphylococcus aureus
strain containing the TSST-1 gene in
Europe: an alert for neonatologists. J Clin
9. Waldvogel FA. Staphylococcus aureus. In:
Mandell GL, Bennett JE, Dolin R, editors.
Mandell, Douglas, and Bennett’s principles
and practice of infectious diseases.
Philadelphia: Churchill Livingstone; 2000.
10. Sanford JP, Gilbert DN, Moellering RC Jr,
Sande MA. The Sanford guide to antimi-
crobial therapy. 17th ed., Belgian/
Luxemburg version. Hyde Park (VT):
Antimicrobial Therapy, Inc.; 2003.
11. Issa NC, Thompson RL. Staphylococcal
toxic shock syndrome. Postgrad Med.
Address for correspondence: Sophie Jamart,
Department of Intensive Care Medecine,
Brugmann University Hospital, 4 Place Van
Gehuchten, 1020 Brussels, Belgium; fax: 32-2-
477-2631; email: sophie.jamart@chubrug-
Are S ARS
To the Editor: The primary mode
of transmission of severe acute respi-
ratory syndrome (SARS) appears to
be through exposure to respiratory
droplets and direct contact with
patients and their contaminated envi-
ronment. However, in summarizing
their experiences during the SARS
outbreaks in Toronto and Taiwan,
McDonald et al. (1) note that certain
persons were very efficient at trans-
mitting SARS coronavirus (SARS-
CoV), and that in certain settings
these so-called “superspreaders”
played a crucial role in the epidemic.
Airborne transmission by aerosols
may have occurred in many of these
cases. The same observation has been
made by others (2–4), but the causes
of these superspreading events and
the reasons for the variable communi-
cability of SARS-CoV are still
unclear. Possible explanations include
specific host characteristics (e.g.,
altered immune status, underlying dis-
eases), higher level of virus shedding,
or environmental factors (1–3).
We hypothesize that superspread-
ing events might be caused by coin-
fection with other respiratory viruses.
Such a mechanism has been identified
in the transmission of Staphylococcus
aureus. Eichenwald et al. (5) showed
that newborns whose noses are colo-
nized with this bacterium disperse
considerable amounts of airborne S.
aureus and become highly contagious
(i.e., superspreaders) after infection
with a respiratory virus (e.g., aden-
ovirus or echovirus). These babies
caused explosive S. aureus outbreaks
in nurseries. Because they are literally
surrounded by clouds of bacteria, they
were called “cloud babies” (5). We
have shown that the same mechanism
also occurs in certain adult nasal car-
riers of S. aureus (“cloud adults”)
(6,7). Reports indicate that viral infec-
tions of the upper respiratory tract
facilitate the transmission of other
bacteria, including Streptococcus
pneumoniae, S. pyogenes, Haemo-
philus influenzae, and Neisseria
meningitidis (8). Moreover, super-
spreading events have also been
reported in outbreaks of viral diseases
such as Ebola hemorrhagic fever and
Some observations suggest that
coinfection with other respiratory
viruses might cause superspreading
events with airborne transmission of
pathogens, including human metap-
neumovirus, have been detected
together with SARS-CoV in some
patients with SARS (4). Second, few
patients with SARS are superspread-
ers, and upper respiratory symptoms
such as rhinorrhea and sore throat are a
relatively uncommon manifestation of
SARS (with prevalences of 14% and
16%, respectively) (4). Thus, some
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 11, No. 4, April 2005637
patients with SARS and upper respira-
tory symptoms might be coinfected
with other respiratory viruses and
become superspreaders. Interestingly,
the report on a SARS superspreading
event in Hong Kong explicitly states
that the superspreader had presented
with a “runny nose” (in addition to
fever, cough, and malaise) (3).
Therefore, upper respiratory symp-
toms might be a marker for highly
infectious SARS patients. Future
investigations, based upon either exist-
ing specimens from the last outbreak
or newly collected specimens from
any future outbreak, should focus on
whether an association exits between
SARS superspreading events and coin-
fection with other respiratory viruses.
Werner E. Bischoff,†
and Robert J. Sherertz†
Switzerland; and †Wake Forest University
School of Medicine, Winston-Salem, North
1. McDonald LC, Simor AE, Su IJ, Maloney
S, Ofner M, Chen KT, et al. SARS in
healthcare facilities, Toronto and Taiwan.
Emerg Infect Dis. 2004;10:777–81.
2. Shen Z, Ning F, Zhou W, He X, Lin C, Chin
DP, et al. Superspreading SARS events,
Beijing, 2003. Emerg
3. Wong T, Lee C, Tam W, Lau JT, Yu T, Lui
S, et al. Cluster of SARS among medical
students exposed to single patient, Hong
Kong. Emerg Infect Dis. 2004;10:269–76.
4. Peiris JS, Yuen KY, Osterhaus AD, Stöhr K.
The severe acute respiratory syndrome. N
Engl J Med. 2003;349:2431–41.
5. Eichenwald HF, Kotsevalov O, Fasso LA.
The “cloud baby”: an example of bacterial-
viral interaction. Am J Dis Child.
6. Sherertz RJ, Reagan DR, Hampton KD,
Robertson KL, Streed SA, Hoen HM, et al.
A cloud adult: the Staphylococcus aureus-
virus interaction revisited. Ann Intern Med.
7. Bassetti S, Bischoff WE, Walter M,
Bassetti-Wyss BA, Mason L, Reboussin
BA, et al. Dispersal of Staphylococcus
aureus into the air associated with a rhi-
novirus infection. Infect Control Hosp
8. Sherertz RJ, Bassetti S, Bassetti-Wyss B.
“Cloud” health-care workers. Emerg Infect
Address for correspondence: Stefano Bassetti,
Division of Infectious Diseases, University
Hospital Basel, CH-4031 Basel, Switzerland;
fax: 41-61-265-3198; email: firstname.lastname@example.org
Route of Infec tion
To the Editor: Melioidosis is an
emerging tropical infectious disease,
the incidence of which is unknown in
many developing countries because of
the lack of diagnostic tests and med-
ical practitioners’lack of awareness of
the disease. It is a potentially fatal dis-
ease caused by the soil bacterium
Burkholderia pseudomallei. Clinical
manifestations, severity, and duration
of B. pseudomallei infection vary
Melioidosis develops after subcu-
taneous infection, inhalation, or
ingestion of contaminated particles or
aerosols. Infection has occurred after
near-drowning accidents (1–3) and
transmission of B. pseudomallei in
drinking water (4). The route of B.
pseudomallei infection is at least 1 of
the factors that influences disease out-
come, thus contributing to the broad
spectrum of clinical signs associated
with melioidosis. Researchers use dif-
ferent routes of delivery of B. pseudo-
mallei in experimental models to
study the pathogenesis of the disease
and the induction of host protection.
Infection by different routes exposes a
pathogen to different components of
the host immune system and may sub-
sequently influence disease outcome.
Despite this difference, no compre-
hensive investigation has compared
the pathogenesis of melioidosis estab-
lished by different routes of infection.
Following intravenous (IV) injec-
tion, BALB/c mice are highly suscep-
tible, and C57BL/6 mice are relative-
ly resistant to B. pseudomallei infec-
tion (5). Using this murine model, we
compared the pathogenesis of B.
pseudomallei infection after introduc-
ing the bacterium by IV, intraperi-
toneal (IP), intranasal, oral, and sub-
cutaneous (SC) routes of infection.
The virulence of 2 B. pseudomallei
strains (NCTC 13178 and NCTC
13179) was compared in BALB/c and
C57BL/6 mice by using a modified
version of the Reed & Meunch (1938)
method. Compared to BALB/c mice,
C57BL/6 mice are less susceptible to
B. pseudomallei infection, regardless
of the portal of entry, thus validating
the model of differential susceptibility
for various routes of infection (Table).
However, as demonstrated by others
(5–7), C57BL/6 mice are not com-
pletely resistant to infection by B.
pseudomallei. Systemic melioidosis
can be generated in C57BL/6 mice by
using different routes of infection, if a
high dose is used. When injected IV
into BALB/c mice, NCTC 13178 is
highly virulent since the 50% lethal
dose (LD50) is <10 CFU. However, if
BALB/c mice are injected SC with
NCTC 13178, the LD50value increas-
es 100-fold to 1 x 103CFU. This value
is equivalent to the LD50of the less
virulent NCTC 13179 delivered SC
The results emphasize that virulence
depends on the route of infection.
The pathogenesis of B. pseudoma-
llei NCTC 13178 infection was com-
pared after infection by the IV, IP, SC,
intranasal, and oral routes. BALB/c
and C57BL/6 mice were administered
570 CFU (equivalent to 60 x LD50
delivered IV) or 3 x 105CFU (equiv-
alent to 60 x LD50delivered IV),
respectively. At 1, 2, and 3 days
postinfection, bacterial loads were
measured in blood, spleen, liver,
lungs, lymph nodes (right and left
axillary and inguinal), and brain by
using methods described previously
A tropism for spleen and liver was
demonstrated following infection by
638 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 11, No. 4, April 2005