Sleeping sickness in Uganda: a thin line between two fatal diseases

Sleeping sickness and geographical area

Disease records for sleeping sickness across Uganda came from the Co-ordinating Centre for Trypanosomiasis in Uganda and from sleeping sickness treatment centres in affected regions. We obtained digital data for Uganda22 from the geographical information system, ArcView 3.2 (Redlands, CA, USA) to determine the size of geographical areas affected through time. The administrative units shown on the map (figure) are districts, the highest administrative unit in Uganda. We determined the distribution of the disease at the level of the subcounty (a lower unit). We calculated the area of each region at risk from the total land area of the relevant administrative (district level) units and determined the population at risk from the 2002 national population and housing census.23

Sequential maps of areas of Uganda affected by sleeping sickness. T b gambiense (in orange) occurs in south Sudan and northwest Uganda, where substantial human population movements have occurred as a result of civil instability. T b rhodesiense (in red) has been spreading since the mid-1980s, and its transmission is now occurring within 150 km of the T b gambiense active focus. The tsetse belt for Glossina fuscipes fuscipes extends right across the region24

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Clinical samples

In southeast Uganda we obtained blood samples from 231 self reporting patients with sleeping sickness from Soroti, Kaberamaido, and Lira districts who attended Serere Health Centre between June 2001 and June 2005 (Soroti: 2001 n = 10, 2002 n = 46, 2003 n = 69, 2004 n = 30, and 2005 n = 55; Kaberamaido: 2004 n = 15, 2005 n = 4; Lira 2004 n = 1, 2005 n = 1). We examined the samples to characterise the trypanosome parasites present (table 1).

In northwest Uganda and south Sudan we examined blood samples from 91 patients from the West Nile/south Sudan focus to characterise the parasites present in human blood. These comprised samples from 27 patients attending Omugo Health Centre, Arua District (West Nile region) and from 64 patients from three health centres in south Sudan (Kiri n = 21, Ibba n = 12, Tambura n = 31) between July and September 2003 (table 1). We also collected samples from 32 pyrexic patients at Akuem Bahr el Ghazal, Sudan, outside the sleeping sickness focus, for use as negative control samples for both T b rhodesiense and T b gambiense (table 1).

We included all patients who presented for treatment during the study and were diagnosed as having sleeping sickness by clinic staff. The molecular tools used in this study were applied post hoc—the diagnosis of sleeping sickness was made in the relevant clinics according to standard protocols.

Polymerase chain reaction analysis

Patients parasitologically positive for sleeping sickness were asked to provide a finger prick sample of blood, which was applied to a DNA binding matrix (FTA card, Whatman). The local health services obtained consent from patients, and agreement or otherwise did not compromise their access to treatment. We prepared FTA cards containing blood samples from sleeping sickness patients for polymerase chain reaction (PCR) as previously described.25 Full details of the PCR methods are provided in the appendix on bmj.com. Briefly, we firstly screened samples from all areas for the presence of human DNA (using human cytoskeletal gamma actin—HCGA), to confirm that the sample contained suitable DNA for PCR amplification. We screened all samples with generic Trypanozoon primers to identify the presence of T brucei sl DNA.26 We screened all Trypanozoon positive samples for T b gambiense (with primers for TgsGP27 28) and T b rhodesiense (with primers for the human serum associated gene SRA16 29). We separated PCR products by agarose (1.5%) electrophoresis containing ethidium bromide (0.2 μg/ml) and visualised them on an ultraviolet transilluminator.

Risk of overlap

Control activities aimed at containing T b rhodesiense in east Uganda have been largely ineffectual.15 17 30 Civil instability in the region and a lack of control measures to contain the spread of disease (such as targeting the animal reservoir by restricting through cattle movements) have resulted in cases of sleeping sickness occurring further and further northwards, closer to the T b gambiense endemic area.

The T b gambiense sleeping sickness focus in north-west Uganda seems to be relatively stable, but the long asymptomatic stage associated with this disease means that, without active surveillance of the human reservoir population, this parasite could spread with movements of displaced peoples in the region. In south Sudan, the absence of disease control activities for eight years after civil disturbance saw the expansion of that sleeping sickness focus and some extremely high disease prevalences (for example, 29% at Ibbe, Marindi County10).

We have shown, using molecular tools, that the cases of sleeping sickness in Kaberamaido and Lira districts of Uganda are indeed due to T b rhodesiense. Although a real risk of overlap with the T b gambiense sleeping sickness focus remains, we found no evidence to indicate that the two active disease focuses have yet converged—that is, there is no T b rhodesiense within the T b gambiense sleeping sickness focus or vice versa. However, the area currently at risk from T b rhodesiense does now overlap with a region affected by a T b gambiense outbreak in 1957.31 The active T b rhodesiense disease focus is now only 150 km from areas currently affected by T b gambiense in the north west of Uganda.

The risk of sleeping sickness spreading by means of the livestock reservoir host continues to be a public health challenge. If infected cattle continue to be traded northwards in the absence of control measures then overlap of the two disease focuses will inevitably occur. If and when overlap does occur, a rapid response including revision of established diagnostic and treatment protocols will be needed to minimise its impact. Such a surveillance programme may be difficult to sustain owing to the unstable nature of the civil situation in this part of the country.28 Currently, livestock for sale in Uganda are required to be treated at their point of origin or before sale; this forms part of the national policy for trypanosomiasis control, although it has been difficult to implement at local level.30 Given the high cost of treating patients and implementing active screening programmes in new regions with limited human health resources, strengthening this policy and encouraging its enforcement by district authorities would seem appropriate.

Economic analysis suggests that the financial benefits of treating the animal reservoir for T b rhodesiense sleeping sickness would more than cover the costs of treatment and may even result in a negative cost per disability adjusted life year averted. Treating cattle increases income from livestock, as the trypanocidal drugs used to clear infection are effective against the trypanosomes that are pathogenic to cattle as well as zoonotic T b rhodesiense. Lowering the incidence of sleeping sickness by treating the animal reservoir will reduce future costs of treating human patients.32 A transsectoral assessment of costs and benefits for control of zoonotic T b rhodesiense, as has been done for control of brucellosis, would seem appropriate.33 Sleeping sickness tends to affect the poorest and most disenfranchised rural communities with the least access to health care. Public health messaging and extension services are urgently needed to improve knowledge and reporting of these diseases.

Recommendations

Surveillance activities should be put in to place to monitor the situation, so that any overlap in disease distribution can be detected at the earliest opportunity. As the parasites involved in T b gambiense and T b rhodesiense sleeping sickness are morphologically identical, such monitoring will inevitably require screening of blood samples and differentiation of the parasites with the molecular methods described here. Although these tools are not yet available at the bedside or penside, the technologies described here are applicable to a suitably equipped in-country regional laboratory targeted at both livestock and human patients at the leading edge of the sleeping sickness focuses.17 26 29 The continent-wide importance of these two parasite species overlapping is such that a properly equipped screening laboratory and staff training should be set up as a matter of urgency. This might take the form of an internationally funded and locally managed facility under the supervision of the relevant authorities in Uganda. Given the economic impact of trypanosomiasis on both the livestock and human health sectors,34 this would be a cost effective proposal for management of this neglected zoonotic disease.

An appendix is on bmj.com