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Skin Features Accompanying Imported Human African
Trypanosomiasis: Hemolymphatic Trypanosoma gambiense
Infection Among Two French Expatriates With
Dermatologic Manifestations
Khaled Ezzedine, MD,*† Hervé Darie, MD,† Michel Le Bras, MD, PhD,† and
Denis Malvy, MD, PhD*†
*Travel Clinics and Tropical Disease Unit, Department of Internal Medicine, Infectious Diseases and Tropical
Medicine, University Hospital Center, Bordeaux, France; †Centre René Labusquière (Tropical Disease Branch),
University Victor Segalen Bordeaux 2, Bordeaux, France
DOI: 10.1111/j.1708-8305.2007.00114.x
D
ermatologic conditions are commonly encountered among returned travellers and longterm residents of the tropics.1 Indeed, many serious
infections acquired during travel or stay in tropical
countries are associated with skin manifestations
that may provide important diagnostic and care
clues. The location of lesions, their pattern, and the
presence of associated symptoms such as pruritus or
fever are important to consider in establishing a
prompt and appropriate diagnosis. This critical
circumstance is illustrated by the following case
reports that describe two French expatriates with
human African trypanosomiasis due to Trypanosoma brucei gambiense who had been diagnosed with
delay, at the hemolymphatic stage of
the disease and within a presentation comprising
characteristic although sparsely reported cutaneous
involvement.
Case Reports
Patient 1
A 37-year-old French expatriate worker was evacuated from Libreville, Gabon, to be admitted in our
clinic because of a febrile illness with fatigue,
anorexia, and arthralgias. The patient had been in
vigorous health 8 months earlier when he experienced the onset of a febrile presentation with prosCorresponding Author: Khaled Ezzedine, MD, Centre
René Labusquière, Université Victor Segalen Bordeaux
2, 146, Rue Léo Saignat, F-33076 Bordeaux CEDEX,
France. E-mail: [email protected]
tration, intermittent posterior-located headache,
severe arthromyalgia, and intense residual fatigue.
Despite the lack of anorexia, the patient acknowledged an involuntary progressive weight loss
accounted to 1 kg/month. Five months later, he
developed recurrent insomnia episodes accompanied with dermatologic manifestations owing for a
diffuse, blanching, macular rash located on the two
arms and on the trunk. Simultaneously, an intense
pruritus of the trunk aggravating an acute paravertebral paresthesia sensation was noted. Three weeks
before admission, he developed laterocervical
lymphadenopathies accompanied by a raise of the
body temperature as high as 41°C.
The patient is a French man working in Central
Africa for 15 years. He had successively lived in
Congo, Cameroon, Guinea, and then in Gabon and
worked in rural forest areas. He had been diagnosed
4 years before for infection with the filarial worm
Loa loa and was efficiently cured. His medical history
was otherwise unremarkable.
At admission, the body temperature was at 39.5°C
and the pulse was 90. The blood pressure was 120/70
mm Hg. On physical examination, a macular rash
involved the right shoulder (Figure 1), the right pectoral part of the anterior trunk (Figure 2), the left
axillae, and the left arm. They appeared as polycyclic
plan plaques of 3 to 9 cm in diameter surrounded
by an intense erythematous peripheral border and a
blancher center. Mobile, tender cervical and occipital lymphadenopathies, 1 to 2 cm in diameter, were
also palpable.
© 2007 International Society of Travel Medicine, 1195-1982
Journal of Travel Medicine, Volume 14, Issue 3, 2007, 192–196
Skin Features Accompanying Imported Human African Trypanosomiasis
Neurological examination was poorly remarkable, showing right and left palmomental reflexes.
The patient was sound. The sensation and muscle
strength were normal.
Laboratory findings failed to reveal anemia; the
erythrocyte sedimentation rate was 55 with a considerable elevated serum IgM antibody level of 25 g/L
(normal range, 0.9–2.9 g/L). Evaluation of a peripheral blood smear as well as a lymph node fluid
aspirate specimen confirmed the diagnosis and
showed trypanosomes. The immunological evaluation by passive hemaglutination antibodies test
showed an elevated serum-specific IgG at a titer level
of 1/64 and a positive enzyme-linked immunosorbent assay test for specific IgM. Examination of the
cerebrospinal fluid (CSF) demonstrated a normal
cell count, a CSF smear after centrifugation without trypanosome, and a slight elevated level of
nonspecific IgM antibodies (2.8 µg/100 mL). The
patient was diagnosed with human African trypanosomiasis probably due to T brucei gambiense, and he
received a diagnosis of the hemolymphatic stage of
the disease, characterized by the absence of involvement of the central nervous system (CNS). He was
efficiently and conveniently treated with a regimen
of 10 doses of intravenous pentamidine isethionate
at a dose of 4 mg/kg over 21 days. The clinical symptoms improved within a few days, the biological
abnormalities resolved, and the serological testing
was negative within 6 weeks. The patient remained
asymptomatic 3 years later.
Figure 1 Circumscribed, polycyclic plan plaque of 7 cm
diameter surrounded by an intense erythematous peripheral border and a blancher center of the right shoulder
(patient 1).
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Figure 2 Circumscribed, macular erythematous rash of
the upper right pectoral area (patient 1).
Patient 2
A 72-year-old man living in Libreville, Gabon, was
referred with a diffuse and intense pruritus. His
medical history was remarkable for chronic prostatitis treated by sequential antibiotic regimen courses
and uncomplicated malaria attacks. The patient had
been in apparent healthy status 5 months earlier
when he developed an irregular febrile presentation,
accompanied by asthenia, an involuntary weight loss
of 10 kg, and an intense and generalized pruritus
predominant to the trunk and the two upper limbs.
The cutaneous condition became rapidly unbearable and was not soothed by the application of local
emollient and corticosteroids, and the administration of oral antihistaminic drugs.
The body temperature was 38°C, and the pulse
was regular at 85. Blood pressure was 110/70 mm Hg.
Tender, mobile, bilateral cervical, axillary lymph
nodes, 1 to 2 cm in diameter, were found. There was
neither hepatomegaly nor spleen enlargement. The
remaining integument and the other physical
findings, including those of the neurological examination, were unremarkable.
Laboratory findings reported an erythrocyte
sedimentation rate at 81 and an elevated aspecific
serum IgG and IgM antibody levels of 29 and 22
g/L, respectively. Examination of a thin smear of
peripheral blood allowed the observation of sparse
trypanosome brucei trypomastigotes. The examination of the aspirate fluid obtained from lymph
node puncture was negative. Examination of CSF
demonstrated a normal cell count, no biochemical abnormalities with normal protein level. Assessment of a sample of CSF after centrifugation
disclosed no evidence of trypanosomal involvement. The serological evaluation of serum sample
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194
by agglutination and indirect immunofluorescence tests were positive, with antibody titer level
accounting at 1/64 and 1/160, respectively. The
serological testing of CSF was negative. Encephalic computerized tomography scan was normal. Electrocardiogram and chest X-ray were
normal.
The patient was diagnosed with human African
trypanosomiasis probably due to T brucei gambiense
with hemolymphatic stage involvement. The patient received a regimen of 10 doses of intravenous
pentamidine isethionate at a dose of 4 mg/kg over
21 days. The symptoms and blood parasitic involvement improved within 5 days. The specific
serological findings became negative over 2
months. Three years later, the patient remained
asymptomatic.
Discussion
Human African trypanosomiasis, also known as
sleeping sickness, is acquired through the bites of
infected bloodsucking tsetse flies of the genus
Glossina.
Concerning the risk of transmission to the expatriates, occupation may affect exposure to tsetse
flies. Indeed, among such overseas residents, an
assessment of environmental hazards to which they
were potentially exposed is an important issue to
assess prompt diagnosis.2,3 Some exotic dermatoses are acquired by individuals who visit rural areas
or wander off the usual tourist routes. Concurrently, the occupation activity of a variety of overseas field-workers may be associated with a
high-risk exposure to a diversity of vectors and infectious agents because of their job requirements
and location.
Human African trypanosomiasis is endemic in a
belt running across Africa. The two patients have
surely been infected by T brucei gambiense, which is
the cause of the infection in West Africa and
accounts for humans to represent the main natural
reservoir. In this epidemiological form of the
disease, transmission of the infection occurs
endemically in rural, forested areas, particularly
near rivers or watering spots, where humans most
frequently come into contact with tsetse flies. So,
tourists rarely acquire T brucei gambiense infection
because they seldom visit the focal rural areas
of Central and West Africa where the disease is
transmitted, although worker residents may be
sparsely concerned.4–6
Contrarily, Trypanosoma brucei rhodesiense is the
agent of disease in East Africa to the east and south
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Ezzedine et al.
of the Lake Victoria. It is a zoonosis primarily
affecting wild animals. It causes sporadic human
cases of infection as human individuals may intrude
into the cycle that normally involves only the
vectors and game animals. It affects especially hunters, honey and beeswax gatherers, and tourists
mostly participating in organized photographic or
hunting safaris.7
African trypanosomiasis is characterized by the
development of a lesion at the inoculation site,
followed by parasitemia, hemolymphatic involvement associated with blood smear invasion and
lymph nodes development at the draining sites, and
eventually invasion of the CNS, which leads to
meningoencephalitis, cerebral atrophy, and death.
Trypanosoma brucei gambiense infection is a quite
indolent lymphoma-like disease, progressing over
months to years, reflecting the partial adaptation of
T brucei gambiense to its reservoir host. A key feature
of the host response is generalized immunosuppression, which is accompanied by polyclonal activation
of B cells and leads to the production of large
amounts of nonspecific IgM, as was observed in our
two reported cases. The first sign of infection is a
painful chancre, which develops at the site of the
tsetse fly bite within 1 to 2 weeks after the bite. It is
typically a large (2–5 cm in diameter), erythematous, indurated, fixed cutaneous swelling, and it
may ulcerate. Unfortunately and contrarily to the
noisy aspect of numerous rubbery inflammatory
lesions occurring during the T. brucei rhodesiense
infection, it is seldom evident in patients infected
with T brucei gambiense4,8 as the infection is often a
unique, circumscribed, indurated nodule and as the
latter may not be reported because the patient
assumes it to be an insect bite or mistakes it for a
focal cellulitis. The frequent localizations are legs,
knees, groin, and axillae. Resolution occurs within a
few weeks.
During the hemolymphatic stage of the disease,
parasites enter the blood stream and intermittent
episodes of high fever develop. The acute septicopyohemic-like course of T. brucei rhodesiense
infection tends to blur the distinction between the
stages of the disease, and patients have a narrower
range of organ failure and hemologic symptoms
before the onset of coma than those infected with
T brucei gambiense.
A characteristic, although exceptionally reported among less than 10% of cases, evanescent
macular rash may be present, with typical polycyclic erythema plaques called trypanides and urticarial rashes occurring on the trunk or the proximal
side of the limbs.9 This rash may be hemorrhagic.
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Skin Features Accompanying Imported Human African Trypanosomiasis
It is more easily observed among patients with
light phototype skin. The presentation of patient 1
is remarkable as these above rarely recognized
eruptive manifestations were on the forefront of
the physical examination. These features are probably underlined by neighbored immunopathogenic mechanisms encountered through other
sepsis-related eruptive conditions such as the erythematous macules known as “rose spots” of typhoid fever due to Salmonella typhi.10 The even
isolated intense pruritic condition is a common
manifestation of tropical imported diseases. It usually accompanies a helmintic infection11 or may
reveal an advanced stage in the course of an unrecognized or treated human immunodeficiency virus
infection/acquired immunodeficiency syndrome
or the onset of a lymphoma involvement. The
other dermatologic signs may account for localized cutaneous edema of the hand, feet, or face.
They are more frequent at the advanced stage of
the infection. The diagnosis of African
trypanosomiasis rests on identification of the parasite that can often be found in blood smear or in
wet blood preparations, with examination of buffy
coat. Lumbar puncture is mandatory in all patients
with confirmed or suspected African trypanosomiasis. Beside the presence of trypanosomes in the
CSF, abnormal findings may suggest invasion of
the CNS. Indeed, a white cell count greater than
5/µL is often used to define the stage of invasion of
the CNS.12,13 Herein, the choice of therapy is determined by the subspecies of trypanosomes and
the presence or absence of involvement of the
CNS. Hemolymphatic T brucei gambiense infection is generally treated with intravenous pentamidine, which can have some adverse effects including
hypoglycemia and hypotension. Therefore, in the
jeopardized issue concerning the indication, the
availability, the efficacy, and the unacceptable
toxicity of the other agents, this drug remains a
satisfactory, tolerated, and efficient treatment.14
In case of involvement of the CNS during T brucei
gambiense infection, either melarsoprol or eflornithine can be used with an evident safer drug profile
for eflornithine. Indeed, treatment with melarsoprol is often accompanied with several adverse effects with the most serious one consisting in a
potentially lethal encephalopathic reaction.14
Finally, avoiding tsetse fly bites is quite illusory for
overseas workers living in the well-known endemic
focal areas. The flies are attracted to bright or
contrasting colors and to the dust and motion of
vehicles. They can bite through thin fabric. Longterm travelers or expatriates should use insect
repellent, and wear wrist- and ankle-length clothing in neutral colors.
Conclusions
Human African trypanosomiasis should be suspected among patients presenting with cutaneous manifestations, lymphadenopathies, and
fever and who live in a recognized endemic focal
area. Prompt diagnosis of infection, mainly before the onset of CNS involvement, should be
established as this form of the disease may be related to easy cure within a convenient therapeutic
approach.
Declaration of Interests
The authors state they have no conflicts of interest.
References
1. Ryan TE, Wilson ME, Kain KC. Illness after
international travel. N Engl J Med 2002; 347:
505–516.
2. Donofrio LM, Millikan LE. Dermatologic diseases of eastern Africa. Dermatol Clin 1994; 12:
621–628.
3. Lucchina LC, Wilson ME, Drake LA. Dermatology
and the recently returned traveller: infectious diseases
with dermatologic manifestations. Int J Dermatol
1997; 36:167–181.
4. Iborra C, Danis M, Bricaire F, Caumes E. A traveller
returning from Central Africa with fever and skin
lesion. Clin Infect Dis 1999; 679–680.
5. Duggan AJ, Hutchinson MP. Sleeping sickness in
Europeans: a review of 109 cases. J Trop Med Hyg
1966; 69:124–131.
6. Spencer HC Jr, Gibson JJ, Brodsky RE, Schultz MG.
Imported African trypanosomiasis in the United
States. Ann Intern Med 1978; 82:633–638.
7. Jelinek T, Bisoffi Z, Bonazzi L, et al. Cluster
of African trypanosomiasis in travellers to Tanzanian national parks. Emerg Infect Dis 2002; 8:
634–635.
8. Malvy D, Djossou F, Weill FX, et al. Human WestAfrican trypanosomiasis with chancre presentation.
Eur J Dermatol 2000; 10:761–762.
9. McGovern TW, Williams W, Fitzpatrick JE, et al.
Cutaneous manifestations of African trypanosomiasis. Arch Dermatol 1995; 131:1178–1182.
10. Hoffner RJ, Slaven E, Perez J, et al. Emergency
department presentations of thyphoid fever. J Emerg
Med 2000; 19:317–321.
11. Caumes E, Carriere J, Guermonprez G, et al. Dermatoses associated with travel to tropical countries:
a prospective study of the diagnosis and management
J Travel Med 2007; 14: 192–196
196
of 269 patients presenting to a tropical disease unit.
Clin Infect Dis 1995; 20:542–548.
12. Miezan TW, Meda HA, Doua F, et al. Assessment of
central nervous system involvement in gambiense
trypanosomiasis: value of the cerebrospinal white
cell count. Trop Med Int Health 1998; 3:571–575.
J Travel Med 2007; 14: 192–196
Ezzedine et al.
13. Lejon V, Büshner P. Cerebrospinal fluid in human
African trypanosomiasis: a key to diagnosis, therapeutic decision and post-treatment follow-up. Trop
Med Int Health 2005; 10:395–403.
14. Pepin J, Milord F. The treatment of human African
trypanosomiasis. Adv Parasitol 1994; 33:1–47.