Fly bites and skin lesion in an asymptomatic traveler returned from Tanzania: Next steps?

Abstract

A returned traveler had three features suggesting a risk for developing East African human trypanosomiasis – geographical exposure (Tanzania), likely tsetse fly bites and a trypanosomal chancre-like skin lesion. However, the traveler was asymptomatic at the time of presentation, raising the issue of how to proceed clinically.

Introduction

Albeit rarely encountered in the United States, the East African form of human African trypanosomiasis (HAT), transmitted by tsetse fly bite, is a serious, rapidly progressive protozoal infection capable of producing potentially fatal multi-organ involvement [1], [2], [3], [4]. In symptomatic returning travelers, early recognition (geographical exposure, tsetse fly bites, presence of a trypanosomal chancre) and prompt diagnosis (microscopy) are the keys to timely, proper treatment [4]. Despite exposure (Tanzania), fly bites and a developing chancre-like skin lesion, the traveler described here, however, was asymptomatic on presentation – raising the question of how to proceed.

Case report

Ten days before returning to the United States from Tanzania, this healthy traveler experienced painful, daytime insect bites on the upper leg while on safari in the Serengeti region. Three days later, a red tender swelling developed at an insect bite site. In an e-mailed request to be seen upon return, the traveler indicated being aware of tsetse flies in the region, that the lesion was increasing in size and firmness despite 5 days of self-medication with twice-daily doxycycline, and that neither fever nor other symptoms had developed. When seen 1 day after return home, the traveler was healthy-appearing, afebrile and asymptomatic. The 3 cm skin lesion (Fig. 1) was red, somewhat tender and while indurated was not fluctuant, ulcerated or draining. There was no lymphadenopathy. A complete blood count was normal.

Fig. 1.

Chancre-like skin lesion on right upper leg. Inset shows magnified view.

Discussion

There were 2 principal concerns in this patient. First, that the skin lesion represented a trypanosomal chancre at the site of a tsetse fly bite, and thus, second, that the traveler could be incubating the East African form of HAT caused by Trypanosoma brucei rhodesiense [1], [2], [3], [4]. The last such imported case of this protozoal infection seen at this New York City teaching hospital was 40 years before [2].

Also known as sleeping sickness, HAT classically occurs in two forms. The West African form, caused by T. b. gambiense and not a geographical consideration in our traveler, is a chronic infection that progresses slowly, often over several years. When imported, it is almost exclusively encountered in migrants and expatriates [1], [5], [6], [7], or, as illustrated by a recent case seen in Texas, in missionaries [8]. In contrast and equally serious, T. b. rhodesiense infection is acute in onset, usually rapidly progressive once expressed clinically and can produce multi-system organ failure [1], [2], [3], [4], [5], [6], [7], [9]. Both forms of HAT are fatal if untreated. Imported cases of HAT in the U.S. are rare [2], [3], [8], [10].

Worldwide, travelers with T. b. rhodiesense infection have primarily been tourists, exposed in national parks or animal preserves in East or southern Africa (largely Tanzania but also Malawi, Uganda, Zambia, Zimbabwe [1], [8]); ~ 90% develop one or more inoculation chancres within 2–14 days after a bite [1], [9], [11]. Chancres are usually 3–5 cm in diameter, show considerable variation in appearance [4], and precede the onset of systemic illness by a variable number of days. The incubation period in travelers from bite to onset of initial Stage I symptoms (e.g., fever, headache, confusion, malaise, musculoskeletal pain, rash [1], [2], [3], [6]) is usually 7–14 days but may range up to 21 or even 28 days [6], [11].

The absence of systemic symptoms 8 days after skin lesion appearance in our patient and 11 days after the likely tsetse fly bite in East Africa was encouraging. Nevertheless, given the prolonged incubation period of T. b. rhodiesense infection and potential clinical consequences, the following pre-emptive/preparatory approach was undertaken:

• 1.Obtain expert advice. A call to CDC’s Division of Parasitic Diseases reassuringly yielded that (a) < 1/100–200 (< 0.5–1%) tsetse fly bites in East Africa transmit trypanosomiasis [10] (more recent estimates suggest < 1/10,000 (< 0.01%) [1]), and that (b) first-line therapy, suramin, was available via CDC should treatment for Stage I (early) infection be necessary [1], [8]. Pentamidine is an alternative initial treatment.
• 2.Attempt a diagnosis. In East African HAT, reliable serologic testing is not available [12]. The diagnosis is secured by microscopic detection of the trypomastigote form, and is usually readily made in symptomatic patients by examining Giemsa-stained peripheral blood smear (preferably a thick smear) or a more concentrated buffy-coat preparation. Trypomastigotes may also be identified as motile forms in fresh wet mount preparations of peripheral blood as well as in stained smears of chancre fluid or cerebrospinal fluid (defining Stage II infection) [1], [9], [10]. In our patient, day 1 blood smears, including of the buffy coat, were negative. Two days later, the patient’s dermatologist at another hospital elected not to aspirate nor unroof the lesion for an impression smear as we had anticipated.
• 3.Provide close, extended follow-up. The patient remained entirely asymptomatic. Out of an abundance of caution, buffy coat smears were repeated at weekly intervals until 28 days had passed since the fly bite. Smears showed no parasites, and the skin lesion, considered to be an uninfected tsetse fly bite, healed within the subsequent 2 weeks.

In the U.S., imported HAT is and will remain rare. Nevertheless, prompt treatment is critical, particularly in the East African form. Thus, as recently re-emphasized by Frean [4], recognition of three features – geographical exposure, a tsetse fly bite and a trypanosomal chancre – along with proper microscopy – are the keys to diagnosis and thus timely therapy and outcome.

Ethical approval

Not necessary.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying image. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

CRediT authorship contribution statement

Henry Murray: Conceptualization, Writing – original draft. Rituparna Pati: Writing – review & editing.

Financial Support

None. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Author Agreement

All authors have seen and approved the manuscript.

Conflicts of Interest

None.