Clinical Presentation of T.b. rhodesiense Sleeping Sickness in Second Stage Patients from Tanzania and Uganda

Abstract

BackgroundA wide spectrum of disease severity has been described for Human African Trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense (T.b. rhodesiense), ranging from chronic disease patterns in southern countries of East Africa to an increase in virulence towards the north. However, only limited data on the clinical presentation of T.b. rhodesiense HAT is available. From 2006-2009 we conducted the first clinical trial program (Impamel III) in T.b. rhodesiense endemic areas of Tanzania and Uganda in accordance with international standards (ICH-GCP). The primary and secondary outcome measures were safety and efficacy of an abridged melarsoprol schedule for treatment of second stage disease. Based on diagnostic findings and clinical examinations at baseline we describe the clinical presentation of T.b. rhodesiense HAT in second stage patients from two distinct geographical settings in East Africa.Methodology/Principal Findings:138 second stage patients from Tanzania and Uganda were enrolled. Blood samples were collected for diagnosis and molecular identification of the infective trypanosomes, and T.b. rhodesiense infection was confirmed in all trial subjects. Significant differences in diagnostic parameters and clinical signs and symptoms were observed: the median white blood cell (WBC) count in the cerebrospinal fluid (CSF) was significantly higher in Tanzania (134cells/mm3) than in Uganda (20cells/mm3; p<0.0001). Unspecific signs of infection were more commonly seen in Uganda, whereas neurological signs and symptoms specific for HAT dominated the clinical presentation of the disease in Tanzania. Co-infections with malaria and HIV did not influence the clinical presentation nor treatment outcomes in the Tanzanian study population.Conclusions/SignificanceWe describe a different clinical presentation of second stage T.b. rhodesiense HAT in two distinct geographical settings in East Africa. In the ongoing absence of sensitive diagnostic tools and safe drugs to diagnose and treat second stage T.b. rhodesiense HAT an early identification of the disease is essential. A detailed understanding of the clinical presentation of T.b. rhodesiense HAT among health personnel and affected communities is vital, and awareness of regional characteristics, as well as implications of co-infections, can support decision making and differential diagnosis.

Human African trypanosomiasis in endemic populations and travellers

“…Different parasite genotypes causing different clinical pic- tures were confirmed for trypanosome isolates on the basis of the SRA (serum resistance associated) gene polymorphisms [34]. A co-infection with HIV or malaria does not influence the clinical presentation of HAT [33].…”

“…rhodesiense HAT (61%) and somnolence (58%) dominated in other foci [27]. In the second stage, fever has less frequently been observed in most studies (14-37%) [27,29,30,33], and fever is only moderate, rarely (4-9%) exceeding 38.4°C [33]. Pruritus, sleeping disorders, reduced consciousness, or neurological signs and symptoms such as tremor, abnormal movements or walking disabilities may predominate in some foci.…”

“…The clinical presentation is similar, but trypanosomal chancres are more frequently seen (5-26%) [27][28][29][30][31], the localisation of enlarged lymph nodes is rather submandibular, axillary and inguinal than nuchal, and oedemas are more frequently observed [28,32]. However, recent descriptions of the clinical presentation show a high variability in different foci [27,33], possibly due to different strains [34]. Whereas fever and headache were the leading symptom in the first stage in some foci (96%) [31], tremor Fig.…”

La maladie du sommeil, fin d’une épidémie ?

“…Bien qu'il y ait eu des notes et des descriptions cliniques allant dans ce sens il y a plus de 60 ans (Apted et al, 1963 ;Stronach, 1963), ce sont les progrè s de la biologie molé culaire et de la caracté risation gé né tique des parasites qui ont permis de confirmer ces donné es et d'affirmer qu'une grande diversité clinique est possible pour les deux affections. Ainsi, pour T. b. g., les formes cliniques vont du porteur asymptomatique jusqu'à l'infection aiguë (Jamonneau et al, 2000(Jamonneau et al, , 2002 et pour T. b. r. un vé ritable gradient dé croissant de sé vé rité est dé crit depuis la Tanzanie au nord, l'Ouganda et vers le Malawi au sud (Kuepfer et al, 2011 ;MacLean et al, 2010 ;Sternberg, 2004). Les infections rapporté es chez les touristes blancs sont plus aiguë s, mais il existe é galement d'importantes variations cliniques dans la population africaine (Foulkes, 1970).…”

Increased acute immune response during the meningo-encephalitic stage of Trypanosoma brucei rhodesiense sleeping sickness compared to Trypanosoma brucei gambiense

“…In both cases, however, early stage patients present unspecific clinical symptoms and signs, while late stage patients are associated to the appearance of neurological disorders, including sleep disturbances [1]. Neurological manifestations have been reported to be more marked in the gambiense form [7,8], while cardiac involvement is considered more important in the rhodesiense one [1,[8][9][10][11].…”