One hundred twenty-one cases met the inclusion criteria: 99 cases from the literature search, 19 cases reported on ProMED-mail, and three cases from the personal archives of the authors. The references of all cases are listed in text S1
The epidemiological data are summarized in and . The description of the groups, the data on clinical findings, laboratory results, diagnostic methods and response to treatment are shown in , , , , , .
HAT in endemic and non-endemic populations (traveler).
Sleeping sickness reported cases over the years in travelers.
Clinical signs and symptoms.
Neurological and psychiatric symptoms.
Forty-five reports on travelers infected with T.b. rhodesiense and 15 reports on travelers infected with T.b. gambiense were included in the analysis of the clinical parameters. Both species presented with fever (T.b. rhodesiense 98%; T.b. gambiense 93%), headache (close to 50% each), and a trypanosomal chancre (T.b. rhodesiense 84%; T.b. gambiense 47%). While insomnia and diurnal somnolence dominate the clinical presentation of HAT in endemic regions, insomnia (T.b. rhodesiense 7%, T.b. gambiense 21%) or diurnal somnolence (T.b. rhodesiense 5%, T.b. gambiense none) have only rarely been described in travelers. Surprisingly, jaundice has been reported in 24% of T.b. rhodesiense infected travelers. The analysis of 14 reports on HAT infected immigrants (all infected with T.b. gambiense) shows that neurological symptoms such as somnolence (46%), motor deficit (64%) and reflex anomalies (14.3%) as well as psychiatric symptoms such as hallucinations (21%) or depression (21%) may dominate the clinical picture. Often, the diagnosis has been missed initially: some patients have even been hospitalized in psychiatric clinics.
While 83% (34/41) of T.b. rhodesiense infected travelers had a history of staying <30 days and 17% (7/41)>30 days within endemic regions, 29% (4/14) of T.b. gambiense infected travelers had spent <30 days and 71% (10/14)>30 days within endemic regions.
The activities determining the risk of exposure in travelers infected with T.b. rhodesiense included: visits to game parks 44/57 (77.2%), hunting safaris 5/57 (8.8%), military missions 4/57 (5.2%), business trips 2/57 (3.5%), and being expatriate 2/57 (3.5%). The main activities determining the risk of exposure in travelers infected with T.b. gambiense were: traveling as tourists 3/16 (18.8%), business trips 5/16 (31.3%) and being expatriate 8/16 (50%).
The putative incubation period was estimated to be ≤14 days in 39/54 (72%) and 15 to 21 days in 11/54 (20%) travelers infected with T.b. rhodesiense. In 4/54 (7%) patients, the time of infection was not precisely known, but - considering the maximal range of exposure - less than 30 days. The incubation period in travelers infected with T.b. gambiense has been <21 days in 4/7 (57%), 21 to 30 days in 1/7 (14%) and >3 months in 2/7 (29%) patients. The incubation period in immigrants was estimated - considering the time of leaving the endemic region and the appearance of the first symptom - to be <5 months in 3/10 (30%), >two years in 6/10 (60%) and even >7 years in 1/10 (10%) patients.
ECG findings have not been routinely described among the reviewed cases. In 14 travelers the following abnormalities have been reported: in the T.b. rhodesiense group 4/10 (40%) have been normal, 1/10 (10%) has shown sinustachycardia, 4/10 (40%) ST- and T- wave abnormalities, and 1/10 (10%) a first degree atrioventricular block. In the T.b. gambiense group, 1/4 (25%) has been normal, 2/4 (50%) have presented a first degree atrioventricular block, and 1/4 (25%) a third degree atrioventricular block.
One single investigation of peripheral blood smears has established the diagnosis in 57/64 (89%) T.b. rhodesiense infected travelers and in 5/9 (56%) T.b. gambiense infected travelers. Repeated examinations have been necessary in eleven patients. In four immigrants, trypanosomes could not be detected by microscopical analysis of peripheral blood or CSF. In one patient, the diagnosis has been established by positive serology and detection of “Mott” cells in bone marrow aspirates; in a second patient by finding “Mott” cells in a brain biopsy; in a third patient by positive serology and histological findings consistent with T.b. gambiense infection; and in a fourth patient by using a PCR assay of the buffy coat and CSF samples.
Travelers infected with T.b. rhodesiense in the first stage have been treated with suramin (42/53 patients (79,2%)). Because suramin was not available, the following alternatives have been used to treat 11 patients: pentamidine (5/53 patients (9.4%)), pentamidine followed by suramin (5/53 patients (9.4%)), and melarsoprol (1/53 patient (1.9%)). All 17 second stage T.b. rhodesiense patients have been treated with melarsoprol. Out of all T.b. rhodesiense infected travelers, three patients died and three had relapses. Two have died of an encephalopathic syndrome due to melarsoprol and one due to severe complications (disseminated intravascular coagulation, cardiac arrhythmia, pneumonia, and generalized seizure). Among the T.b. gambiense infected travelers, no patient has died.
T.b. gambiense infected patients (both travelers and immigrants) with first stage HAT have been treated with pentamidine (10/14 patients (71.4%)), suramin (2/14 patients (14.3%)) and eflornithin (2/14 patients (14.3%)). The patients in second stage HAT have been treated with eflornithine (17/29 patients (58.6%)) or melarsoprol (12/29 patients (41.4%)).