Human African Trypanosomiasis (African Trypanosomiasis, African Sleeping Sickness)

Are You Confident of the Diagnosis?

What you should be alert for in the history

Patients develop human African trypanosomiasis (HAT) only after visiting rural areas of sub-Saharan Africa. A painful chancre may develop at the site of a Tsetse fly bite. A targetoid macular trypanid (Figure 1) may accompany or follow intermittent high fevers. Patients with the Eastern or Rhodesian form of HAT develop sleep disturbances, neurologic problems, and deep delayed hyperesthesia within weeks or a few months of exposure.

In 70-80% of Eastern HAT patients, a painful, indurated, violaceous chancre measuring 2-5cm in diameter develops at the bite site 5-15 days after inoculation (Figure 2, Figure 3). The chancre ulcerates, forms an eschar, and heals by 3 weeks after its appearance. Chancres are rare in Western HAT. Trypanosomes multiply in the chancre and then spread to draining lymph nodes.

Figure 2.

Western HAT may be asymptomatic for months to over a year, while Eastern HAT victims typically develop hemolymphatic (early or stage I) disease as the chancre heals. Stage I disease due to multiplication of parasites in the blood and lymph nodes is characterized by intermittent fevers (40-41^oC), pruritus, malaise, myalgias, arthralgias, lymphadenopathy, and occasional hepatosplenomegaly. Signs and symptoms are more severe in non-native patients.

Characteristic findings on physical examination

The most specific stage I sign is the trypanid, a macular, targetoid, erythematous eruption that occurs 6-8 weeks following onset of illness (Figure 4). As the trypanid resolves, it reveals underlying purpura (Figure 5).

Figure 4.

Figure 5.

Visible lymphadenopathy tends to involve the posterior cervical (Winterbottom’s sign) and supraclavlcular nodes in Western HAT and the axillary and epitrochlear nodes in Eastern HAT. Cutaneous findings include localized facial edema, petechiae, erythema nodosum, ichthyosis, and purpura.

Expected results of diagnostic studies

Trypanid histology is nonspecific. The leading edge of a targetoid lesion reveals lymphocytic spongiosis and superficial perivascular lymphocytic infiltrates (Figure 6). The center of a targetoid lesion demonstrates lymphocytic spongiosis, a superficial perivascular lymphocytic infiltrate, neutrophils, and leukocytoclasia (Figure 7, Figure 8). Trypanosomes are not found in trypanid biopsies.

Figure 6.

Figure 7.

Figure 8.

Trypanosomes rapidly change their variant surface glycoprotein coat to evade the host immune system. The Western gambiense parasite is less efficient at this antigenic change, and this may explain why Western HAT progresses more slowly than Eastern HAT.

Diagnosis confirmation

Diagnosis requires demonstration of trypanosomes in a Giemsa-stained blood smear or a lymph node aspirate. Slides must be reviewed within 20 minutes of obtaining samples, since the trypanosomes easily lyse. Because the Eastern Rhodesian form of disease is more virulent, the 15-30 micron, flagellated trypanosomes are easily found on a routine blood smear. Finding parasites in Western HAT patients often requires concentration of the blood to form buffy coats.

Every patient with HAT must have a lumbar puncture performed for staging purposes. To avoid transferring trypanosomes from the blood during the procedure, it is best to wait 24 hours after initiating therapy for stage I disease so that parasite blood levels significantly drop. Organisms are difficult to find in cerebrospinal fluid (CSF). In the absence of parasites, a positive CSF is characterized by finding more than five leukocytes per microliter, a protein level above 370mg/L, or the presence of high levels of IgM.

Occasionally, Mott cells are found. These are large eosinophilic plasma cells which have not disgorged their large quantities of IgM. Rodent inoculation with CSF can also prove the presence of trypanosomes.

The most common cause of a chancre-like lesion in a traveler to Africa is a furuncle due to Staphylococcus aureus or Streptococcus. The most common cause of fever in a hospitalized patient recently returning from Africa is malaria, and a blood smear is necessary for diagnosis.

Who is at Risk for Developing this Disease?

Western (Gambian) HAT develops in western and central Africa, while Eastern (Rhodesian) HAT occurs in eastern and southern Africa. As of 2009, only 18 countries reported new cases of HAT, and over 70% were due to Western HAT in the Democratic Republic of the Congo (DRC).

Only the DRC and the Central African Republic reported more than 1000 cases per year, and only four other countries (Angola, Chad, Sudan, and Uganda) reported 100-1000 cases per year. Western HAT accounts for over 95% of cases. Total cases decreased from about 38,000 in 1998 to less than 10,000 in 2009. The World Health Organization official estimate of 30,000 new cases annually assumes a threefold underreporting error.

Urban area travelers and citizens are not at risk for HAT. People contract western HAT in poor, remote rural areas while fishing, hunting, farming, and washing clothes. Eastern HAT develops among hunters, game wardens, and tourists on safari in game parks, particularly in Tanzania, but also in Botswana, Rwanda, Kenya, and Malawi. Western HAT is rare in short-term tourists. The United States has averaged about one case of HAT per year for the last 40 years, and 90% of patients had the Eastern form.

What is the Cause of the Disease?

Two morphologically identical subspecies of the unicellular protozoan parasite Trypanosoma brucei cause HAT: T. b. gambiense causes the Western form and T. b. rhodesiense causes the Eastern form. Parasites are transmitted by tsetse flies of the genus Glossina. Humans serve as the primary reservoir for T. b. gambiense, and cattle are the primary reservoir of T. b. rhodesiense.

Both forms follow a painful tsetse fly bite. Both male and female flies bite during daylight and are attracted to dark and bright clothing; neutral-colored clothing that covers to the ankles and wrists is recommended.

Systemic Implications and Complications

Untreated stage I patients develop central nervous system (CNS) (late or stage II) disease. Trypanosomes actively cross the blood-brain barrier within weeks to a few months in Eastern disease and after months to years in Western HAT.

Patients with CNS disease complain of severe headaches, disturbed sleep, and daytime somnolence. The most specific sign of stage II is Kerandel’s deep delayed hyperesthesia: delayed pain out of proportion to the stimulus following a sharp squeeze or blow to the soft tissues. Other signs include tremor, fasciculations, general weakness, limb paralysis, hemiparesis, akinesia, Parkinsonian behavior, psychoses, or abnormal movements.

Coma and death ensue within a few months (Eastern HAT) or 3 years (Western HAT) without treatment.

Treatment Options

Five drugs are used to treat HAT

Suramin

Pentamidine isethionate

Melarsoprol

Eflornithine

Nifurtimox

Optimal Therapeutic Approach for this Disease

Optimal treatments for HAT are summarized in Table I. As soon as you have diagnosed a patient with HAT, call the Centers for Disease Control and Prevention in Atlanta (CDC, if you live in the United States) or the World Health Organization (WHO, outside the United States). One of these organizations will get you the medication you need and explain how to give it to your patient.

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