Download Mediterranean Spotted Fever in Travelers from the United States

Mediterranean Spotted Fever in
Travelers from the United States
Leonavdo A. Palau and George A.Pankey
Background: We wish to increase awareness by US. physicians of the clinical manifestations and diagnosis of Mediterranean
spotted fever (MSF), and to determine the incidence of MSF among travelers returning to the United States from endemic
areas.
Methods: We report a case of a 56-year-old female physician from New Orleans who returned from a 3-week safari trip
t o Zimbabwe and Zambia with clinical findings of MSFThe diagnosis was confirmed with a greater than fourfold rise i n
titer of IgM and IgG antibody t o Rickettsia conoriion acute and convalescent sera (16 days apart) using indirect immunofluorescence technique. In addition, w e conducted a MEDLINE computer search of published MSF cases in U.S. travelers
returning t o the United States and obtained the United States data over the past 20 years from the Centers for Disease
Control and Prevention (CDC).
Results: Less than 50 imported cases of MSF have been reported and confirmed by the CDC. Only seven cases have been
published in the literature and none in the last 7 years.
Conclusions: Despite the increasing incidence of MSF i n Europe, Asia and Africa, and the high number of U S . citizens
traveling to these endemic areas, only a few imported cases of MSF i n travelers have been reported in the United States.
Physicians in the United States are not familiar with the clinical findings and diagnosis of MSF; therefore this disease is
underrecognized in the majority of cases.
disease.The most common rickettsial disease in returning U.S. travelers is Mediterranean spotted fever.
Mediterranean spotted fever (MSF) o r Boutonneuse fever is an acute infectious disease caused by Rickettsia conorii.This disease was first described by Conor and
Bruch in Tunisia in 1910’ and the name MSF was
adopted in 1932 at the First International Congress of
Mediterranean Hygiene. It is transmitted to man by the
bite of various European,AErican and Asian species of ixodid ticks, primarily the dog tick Rkipicepkalus sanguineu.q.
Neither the Rickettsia conorii organism nor the ticks
inhabit the North American continent.
This disease is endemic to southern Europe (Italy,
France, Spain, Portugal);subSaharan Africa; Middle Eastern areas adjacent to the Mediterranean, Black and
Caspian Seas; and India. It occurs in urban areas as well
as in the bush. In recent years a dramatically increased
incidence of this disease in endemic areas has been
noted.* Therefore, travelers visiting these countries are at
risk for infection. Rickettsia1 infection is now the third
most frequent cause of fever in travelers returning to
Switzerland’; however, despite the increasing number
of U.S. residents traveling to these endemic areas, only
seven cases in travelers returning to the United States have
been published,and none since 1990.&’This striking finding may be due to the lack of awareness by physicians
in the United States of the clinical characteristics and epidemiology of this disease.The Centers for Disease Control and Prevention (CDC) Atlanta,Georgia, has clinically
and serologically identified less than 50 cases of MSE
The rickettsiae are obligate intracellular bacterial
organisms. They are maintained in nature through a
cycle involving vertebrate hosts (reservoir) and arthropod vectors. Humans become infected when they are incidentally bitten by an infected vector (tick, lice, etc.) and
are not involved in maintaining or propagating the disease; with the exception of epidemic typhus, no transmission occurs from person to person.
The rickettsiae are divided into spotted fever and
typhus groups based on antigenic differences and intracellular growth. The spotted fevers have restrictive geographic distribution and affect different populations in
different parts of the world, reflecting the existence of a
particular reservoir and tick vector. Among the spotted
fever group, only Rocky Mountain spotted fever and
rickettsialpox are native to the United States. However,
modern air travel has made it possible for a U.S. resident
to return from any part of the world within the incubation period or with symptoms ofa spotted fever rickettsial
Leonard0 A. Patau, MD, and George A. Pankey, MD:
Department of Infectious Diseases, Ochsner Clinic and Alton
Ochsner Medical Foundation, New Orleans, Louisiana.
This paper was presented at the 5th International
Conference ofTrave1 Medicine in Geneva, Switzerland,
25 March 1997.
Reprint requests: Dr. Pankey, Ochsner Clinic, 1514 Jefferson
Highway, New Orleans, LA 70121, USA.
JTravel Med 1997; 4:179-182.
179
180
However, this disease is not reportable in the United
States, and the CDC,Atlanta, Georgia, does not keep track
of the number of new cases ( K u s d l Regnery, PhD,
CDC,personal coniniunication, November 1996),making it difficult to establish its incidence in travelers returning froni endemic areas.
We report a case of MSF in a New Orleans resident
who contracted this disease during a safari trip to Africa.
Case Report
A 56-year-old, previously healthy female physician
presented to the Ochsner Travel Clinic on 24 June 1996,
2 days after returning from a 3-week safari trip to Africa.
She complained of fever, chills, malaise, a maculopapular rash, and a necrotic skin lesion on the right side of
the abdomen.
She had arrived in the city of Harare in Zimbabwe
on 4 June 1996 and immediately started taking doxycycline 100 mg daily for malaria prophylaxis, but discontinued 3 days later due to a vaginal yeast infection.
Much of the time in Africa was spent in the bush, including canoeing in the Zambesi River (between Zimbabwe
and Zambia) and camping in sandy and grassy areas
along the shore of the river. O n 15June, she noticed an
erythematous lesion in the right lower abdomen consistent with a tick bite,although she did not recall renioving any ticks from her skin. O n 16June, she noticed the
onset of high fever (38.2 to 39.4”C),chills, and malaise.
She did not have diaphoresis,headache, myalgia or tachycardia.A maculopapular rash was observed on the left arm
and both thighs.These symptoms persisted and on 19
June, she flew to Capetown, South Africa, seeking medical attenti0n.A clinical diagnosis of malaria was excluded,
and empiric treatment with doxycycline 100 nig twice
daily was begun o n 20 June. She returned to the United
States o n 22 June.
At the time of presentation, she was symptoniatically
much improved, though the skin lesion and the rash persisted. She was alert and in no distress. Her temperature
was 37OC, heart rate 62 beats per minute and regular, and
blood pressure 138/76 niinHg. There was no lymphadenopathy, and cardiac, pulmonary, and abdominal
examinations were normal. There was a nontender
3x3 cm erythematous skin lesion with a dark center over
the right lower abdomen and a maculopapular nonpruritic rash over both thighs and left arm.The rash did not
involve the palms and soles.
Laboratory studies revealed the following values;
white cell count, 3.3X10’/nim3, with 64% segmented
neutrophils, 28%)lymphocytes and 8% monocytes; hemoglobin, 12.6 g/dL; hernatocrit, 36%; platelet count,
235 X I 0‘/uim3;and erythrocyte sedimentation, 5 mni/h.
Blood chemistry profile was normal. Liver function tests
Journal o f Travel Medicine, Volume 4, N u m b e r 4
were mildly elevated:aspartate aminotransferase,53 U/L;
alanine aminotransferase 47 U/L; and lactate dehydrogenase (LDH), 281 U/L.
Serologic tests performed at Specialty Laboratories,
Los Angeles, showed a rise in indirect fluorescent IgM
antibody titers to Rickettsia ronorii from less than I :20 o n
26 June to greater than 1:320 on I2 July (normal range
less than 1:20). IgG antibody rose from 1 5 4 to greater
than 1:1024 (normal range less than 1:16) in the same
period of time.
The patient received a total of 10 days ofdoxycycline
and fully recovered.
Discussion
The incubation period of MSF is about 6-1 0 days,
and the natural duration of illness is froni 12-21) days.
The disease begins with fever, malaise, headache, niyalgia and conjunctival injection.’The niajority of patients
(80%) have a primary lesion at the site of the tick bite
(“tache noire”).This lesion is usually present at the onset
of fever and consists of a small ulcer with a black center
and a red areola (Fig. l ) . A maculopapular rash appears
around the fourth day and involves most of the body
including palms and soles (Fig. 2).This rash is hndamental
for the diagnosis. Five percent of the patients develop a
severe form of the disease, and 2.7%)die.
The laboratory findings are nonspecific. The total
leukocyte count may be low. Elevation of liver function
tests and LDH levels occur in more than 75% of cases.
Hyponatremia and thrombocytopenia are common.
MSF must be differentiated from African tick-bite
fever (ATBF) (Table I ) , a recently described disease
caused by Rickettsia nfYicae and transmitted by Amblyomma
ticks (buffalo ticks).”’” Unlike MSF, this disease is characterized by multiple “taches noire,” lymphadenopathy,
lymphangitis, eschar edema, the absence of rash, and the
production of increased IgA serum levels.‘(I
MSF should be suspected in any traveler returning
tiom an endemic area with fever, maculopapular rash, and
the distinctive “tache noire.”Traditionally the causative
organism has been identified from epideniiologic, clinical, and serologic data. Indirect inimunofluorescence
antibody assay of acute and convalescent sera is the most
widely used diagnostic test.This serologic test can be nude
species-specific. However, these antibodies may cross-react
with the antigens of the other members of the spotted
group, especially R. rirkettsii and R. akari, making this test
unreliable to identify the causative agent with certainty.
Other tests can be performed to confirm the diagnosis,
such as isolation of R. cunorii from blood culture with the
use of the shell vial culture technique’ and demonstration
of R. ctinorii in cutaneous lesions by immunofluorescence
staining” or polynierase chain reaction amplification.’3
’
Palau and Pankey, Mediterranean Spotted Fever
181
Figure 1 Typical "tache noire" skin lesion on the abdomen
of a patient with Mediterranean spotted fever.
Figure2 Maculopapular rash overthe legs of a patientwith
Mediterranean spotted fever.
When travelers return with equivocal clinical manifestations from areas where rickettsia species overlap (MSF
and ATBF in Africa),specificWestern ininiunoblot analysis against a specific protein antigen can identify the
species.l o
infection; therefore, it is contraindicated for therapy of
MSF."'
Treatment
Therapy with doxycycline, ciprofloxacin, or chloraniphenicol is effective.Antibiotics shorten the duration
of symptoms and prevent possible coinplications and
recurrences. T h e optimal duration of treatment is
unknown.Although most authorities recommend I- or
2-week courses of antibiotics, a single dose of 200 nig
of doxycycline or two single doses over a 24-hour period
have been shown to be effective as well.14
Ciprofloxacin (750 mg q32h PO for 1 week) may
be more effective than doxycycline, since it is bactericidal, has fewer side effects, and is at lower risk than doxycycline for development of resistance."
Trimethoprim-sulfamethoxazole increases the pathogenic potential of R. ronovii and the severity of the
Prevention
U.S. travelers to endemic areas should avoid contact
with ticks by the use of repellents and protective clothing.The body should be searched regularly for ticks, and
the ticks should be promptly removed. Malaria prophylaxis with doxycycline may abort or prevent this disease.
Summary
Modern transportation enables U.S. residents to
travel to regions where R. conorii is common and to
return harboring Mediterranean spotted fever.This is particularly true for tourists visiting subSaharan Africa countries and southern Europe where the incidence of MSF
is increasing. Our case illustrates the need for physicians
in the United States to be familiar with the epideiniology and clinical characteristics of MSF and to advise travelers of the risk of acquiring this disease.
Table 1 Clinical Differences between Mediterranean Spotted Fever and African 5ck-Bite Fever
Characteristic
Agent
Tick vector
Skin rash
Tache noire
Lymphadenopathy
Lymphangitis
Eschar rdenia
Serum IgA
fljican Tick- Bite Fever
Rickettsia conorii
Rliipicephalus sanguineus
present
usually one
unconiiiion
absent
uncommon
normal
Rickettsia afrirae
Amhlyonirnn Iiebrawrr
absent
nlultlple
coninion
common
common
sometinier elevated
J o u r n a l o f T r a v e l M e d i c i n e , V o l u m e 4, Number 4
182
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Tourists canoeing on the Zambesi river. Submitted by the authors.