Spatial Analysis of Sleeping Sickness, Southeastern Uganda, 1970–2003
http://www.100md.com
《传染病的形成》
University of Guelph, Guelph, Ontario, Canada
University of Veterinary Medicine, Hannover, Germany
Makerere University, Kampala, Uganda
International Livestock Research Institute, Nairobi, Kenya
Sleeping sickness reemerged in southeastern Uganda in the 1970s and remains a public health problem. It has continued to spread north into new districts, and gaps remain in the understanding of the causes of its spread and distribution. We report the distribution and magnitude of sleeping sickness in southeastern Uganda from 1970 to 2003. Data were collected from records of the Ugandan Ministry of Health, individual sleeping sickness treatment centers, and interviews with public health officials. Data were used to develop incidence maps over time, conduct space-time cluster detection analyses, and develop a velocity vector map to visualize spread of sleeping sickness over time in southeastern Uganda. Results show rapid propagation of sleeping sickness from its epicenter in southern Iganga District and its spread north into new districts and foci.
Sleeping sickness is the human form of African trypanosomiasis (caused by Trypanosoma spp.), a protozoal parasitic disease affecting humans, livestock, and many sylvatic species in sub-Saharan Africa. It is transmitted by the tsetse fly vector (Glossina spp.) and in cattle is a serious constraint to livestock development in sub-Saharan Africa (1–3).
The acute form of sleeping sickness, which is caused by Trypanosoma brucei rhodesiense and is predominant in eastern and southern Africa (4–6), is present in southeastern Uganda . Sleeping sickness is a serious public health problem in this region; epidemics have occurred in 1901–1915, 1940–1946, and 1976–1989 (3). More recently, spread of sleeping sickness into areas previously thought to be free from the disease has highlighted gaps in the ability of current research to explain and predict the distribution of infection (7).
In 1976, an outbreak was detected in Luuka County in western Iganga District, outside the traditional fly zone. This was the beginning of an extensive epidemic that eventually spread throughout southeastern Uganda. This outbreak occurred during a time of great political instability and civil conflict in Uganda, which contributed to a reduction of resources and services for sleeping sickness (8). Although the incidence of sleeping sickness decreased in southeastern Uganda in the early 1990s, it continues to persist and spread in 2005. An outbreak was detected for the first time in Soroti District in 1998 (7), followed by continued spread north into Kumi, Kaberamaido, and Lira Districts (9,10). Historical analyses of sleeping sickness in southeastern Uganda can improve disease control by increasing understanding of the context and trends of the disease, as well as identifying variables associated with these trends. Additionally, historical analyses may validate hypothesized processes.
We describe and characterize the spatial distribution of T. b. rhodesiense sleeping sickness in southeastern Uganda for a 34-year epidemic period (1970–2003). We hypothesize that sleeping sickness in southeastern Uganda is driven by 2 dominant processes. In process A, in regions where disease occurs or has recently occurred, localized outbreaks are triggered by processes that increase tsetse populations or by changes that increase human-tsetse contact. In process B, in regions where disease has not recently occurred, spread is facilitated by movement of infected livestock into uninfected regions.
Methods
Study Area
The study area in southeast Uganda in eastern Africa is subdivided into 17 districts, 46 counties, and 254 subcounties. The region has an area of ≈55,000 km2 and a population of ≈9 million (11). Thirteen percent live in the capital of Kampala (11), and the remainder live in predominantly rural areas dominated by livestock and subsistence farming (12,13).
Data Collection
Cross-sectional sleeping sickness data from 1970 to 2003 were collected retrospectively in 2004 to identify case counts and measures of disease magnitude per subcounty per year. Data were collected for all available records of sleeping sickness patients in southeastern Uganda. Data availability and reliability varied between years on the basis of quality of surveillance and primary data collection, as well as availability of records and recall bias for secondary data collection. Reliability of data for 1986 to 2003 was considered moderate to high, but reliability of data for 1970 to 1986 was low to moderate. Evaluation and review of data by public health officials concluded that information on disease prevalence and absence was reliable for most years, but measures of disease magnitude were less reliable before 1986.
Since 1999, sleeping sickness data summaries have been provided by the National Sleeping Sickness Control Program at the Ugandan Ministry of Health. For data before 1988, no centralized collection of records exists beyond district summaries; sleeping sickness case data remain in records at individual treatment centers. Data before 1988 were collected retrospectively in 2004 during visits to all treatment centers active in the 1980s. In many cases, record books were poorly stored, damaged, had lost pages, or were missing . Case definition was based on the primary diagnosis; all cases recorded in record books were included in this study. Cases were assigned to a year based on the patient's date of admission.
Gaps in the dataset increased before 1986. Limited data were available for the late 1970s, and no quantitative data were available for the early- to mid-1970s. Interviews were conducted with public health officials to complement and extend 1970s and 1980s data. These officials were chosen by identifying Ugandans actively involved in senior positions in sleeping sickness prevention and control from 1970 to the present and those who could be contacted. They included veterinary and public health managers at the National Ministry of Health or District Medical or Veterinary Office levels. Interviews were used to verify data for the 1980s and to classify disease magnitude for the 1970s.
Sleeping sickness magnitude was classified into 1 of 5 categories for each subcounty for each year: 1) no cases, 2) preepidemic (1–4 cases per year per subcounty), 3) low epidemic (5–15 cases per year per subcounty), 4) high epidemic (16–100 cases per year per subcounty), and 5) extreme epidemic (>100 cases per year per subcounty). These thresholds were based on anecdotal guidance from preliminary interviews and defined to facilitate standardized definitions of magnitude during subsequent interviews. Interviewer information was compared to available sleeping sickness records and the literature. These results were used to develop a classification database of disease magnitude by subcounty and year. Resulting data and maps were presented to informants for discussion and validation at follow-up interviews in 2005.
The boundaries of political regions changed greatly during the 34-year study period. Aggregation of subcounty data reduced the number of subcounties from 254 in 2004 to 225 for the current study period. Temporal resolution of data is consistent, and aggregation of 29 subcounties is assumed to have little effect on overall analyses.
Data Analysis
Case counts from 225 subcounties in southeastern Uganda for 34 years (1970–2003) were aggregated into 5 temporal periods for descriptive and geographic cluster analysis on the basis of epidemic progression and data availability: 1970–1975, preepidemic; 1976–1979, epidemic increase; 1980–1888, epidemic peak; 1989–1997, epidemic decrease; and 1998–2003, epidemic tail. Mean case counts per subcounty per year were calculated for periods in which case counts were available (1980–1988, 1989–1997, and 1998–2003). For earlier periods (1970–1975 and 1976–1979), only ordinal data were available. Therefore, data midpoints were calculated by using the mean of the maximum and minimum ordinal values rounded to the nearest whole number in the direction of the mode. These data were used to develop maps averaging the annual incidences of sleeping sickness for each subcounty during the interval period. Averages of annual incidence for intervals after 1980 were reclassified as sporadic (<5 cases/year), low epidemic (5–15 cases/year), or high epidemic (>15 cases/year) to match ordinal data categories for 1970s data.
To identify clusters of sleeping sickness in southeastern Uganda from 1970 to 2003, the space-time scan statistic (14) was used (SaTScan version 5.1 software for spatial and space-time scan statistics available from http://www.satscan.org/ [Kulldorff, Boston, MA, USA and Information Management Services Inc., Silver Springs, MD, USA]). The incidence proportions of the 225 subcounties were assumed to follow a Poisson distribution according to the underlying population size. Cluster analysis results include space-time clusters with no geographic overlap of clusters allowed and a maximum allowable cluster size of 50% of the population. Space-only and time-only clusters were excluded. Primary and secondary clusters at a significance level of α = 5% are reported.
Sleeping sickness data were used in the form of case counts per year per subcounty for post-1980 records. For 1970s data, recorded values represent ordinal data (i.e., low, medium, high) rather than case counts. These were transformed to case counts by applying the ordinal minimum value to each record. Population data are based on the 1980, 1991, and 2002 population censuses for Uganda (11). The first 3 analysis periods (1970–1988) used 1980 census records for population counts. Analyses for the periods 1989–1997 and 1998–2003 are based on 1991 and 2002 census records, respectively.
A vector velocity map (15) of sleeping sickness spread was developed by using trend surface analysis (TSA) (16,17). TSA is a global smoothing method using polynomials in geographic coordinates, as defined by the central point of each subcounty polygon. In this case, a trend surface of the year of the first reported sleeping sickness case for each subcounty was used to explore and identify diffusion patterns and corridors of spread over time.
The year of the first recorded case was identified for subcounties in the database. Eighty-nine of 225 subcounties with no recorded cases in the 1970–2003 study period were excluded. The x- and y-coordinates of subcounty centroids were calculated from a UTM projection shapefile of southeastern Uganda using ArcMAP (ArcGIS 9, Environmental Systems Research Institute, Redlands, CA, USA). Least square regression using linear, quadratic, cubic, and higher-order polynomials of the x- and y-coordinates to predict year of first reported case was conducted in R (Foundation for Statistical Computing, Vienna, Austria, available from http://www.R-project.org). Partial differential equations (Δyear/ΔX and Δyear/ΔY) were derived from the fitted model, giving a vector of the magnitude (slope) and direction for each location. The square root of the slope equates to the velocity of diffusion.
Results
Epidemic Curve
Incidence Maps and Cluster Detection
1970–1975: Preepidemic
1976–1979: Epidemic Increase
1980–1988: Epidemic Peak
1989–1997: Epidemic Decrease
1998–2003: Epidemic Tail
Trend Surface Analysis
The results from trend surface analysis are summarized in a velocity vector map (Figure 9). The velocity and direction of diffusion for each coordinate location were mapped to show the movement and instantaneous rate of T. b. rhodesiense sleeping sickness diffusion in southeastern Uganda over the study period. TSA with high-order polynomials is sensitive to data anomalies at the edge of the study area (15). Less data are available at the study area boundaries; velocity vector size and direction are therefore less reliable and may not be accurate at the edge of the study area. For these reasons, 9 velocity vectors were removed from the vector diffusion map (Figure 9).
The average velocity of sleeping sickness spread over 34 years in southeastern Uganda from 1970 to 2003 was 5 km/year. Velocity of movement was highest early in the epidemic (Figure 9), when sleeping sickness spread out of its primary focus in southern Iganga District. The epidemic diffused outward in a relatively constant sphere of diffusion from this epicenter. A corridor of movement can be observed on the eastern fringe of the study area, moving through Busia and Tororo Districts. However, this fringe area should be interpreted with caution because of potential edge effects. The disease moved distinctly north and east into Soroti District. Areas of most rapid spread appear to be the extensions of these 2 corridors north from Soroti and Tororo. These results are consistent with recent detection of cases in the districts of Kumi, Kaberamaido, and Lira (9,10) adjacent to or north of Soroti. Velocity vectors also showed spread west and east. However, Figures 4–8 suggest that much of this horizontal diffusion occurred before the 1990s.
Discussion
The reliability of data for the 1970s and 1980s is subject to detection and recording bias associated with periods of passive surveillance, missing record books, and recall bias of interviewees. The creation of additional treatment centers over the study period and differential quality of diagnostic and treatment facilities throughout the study area may contribute to spatial bias in the data. Odiit et al. (20–22) discuss the potential for misdiagnosis of cases, selective entry bias around treatment centers, and underdetection of sleeping sickness. Aggregation of cases by subcounty reduces the potential for clustering around individual treatment centers, and unless differential misdiagnosis occurs, it will not critically affect the spatial patterns seen. The data must be interpreted with caution in the context of data reliability and potential biases. Results should be considered exploratory and descriptive; data are not appropriate for direct causal inferences. The results are, however, useful for characterizing broad trends; where historical trends in processes observed are consistent with hypotheses, results can inform current and future research.
T. b. rhodesiense sleeping sickness in southeastern Uganda from 1970 to 2003 followed a pattern of radial spread from its center in southern Iganga District. From 1976 to the 1990s (Figures 4–7), the epidemic trend coincided with civil unrest and political instability in the country. The increase in the epidemic (1976–1979) occurred at a time of increasing political and economic instability, while the peak epidemic period (1980–1988) occurred during the height of political and economic collapse. The decrease in the epidemic (1989–1997) also coincides with increasing stabilization of politics and civil unrest in Uganda. The epidemic trend observed is consistent with our hypothesis (process A) that incidence increases in regions with a history of infection because of changes in human-vector exposure that push the probability of transmission above the required threshold for focal outbreaks. Uganda in the 1970s and 1980s experienced extensive internal displacement of the rural population, illegal human and cattle movements, growth of favorable tsetse habitats on cotton and coffee plantations, and collapse of sleeping sickness prevention and control activities (8,19,23). These events likely contributed to increased human-vector contact and sleeping sickness transmission in the districts around the preepidemic zone of infection.
After the decrease in the epidemic in the 1990s, new outbreaks have been observed in Soroti (1998, Figure 8), Kaberamaido, Kumi, and Lira (2004–2005) Districts (7,9,10). The introduction of the parasite into Soroti District has been linked to cattle restocking from infected southern districts (7). Whether more recent spread into new districts is related to cattle movements is unclear. Postepidemic spread into previously uninfected and peripheral districts since the late 1990s is consistent with our hypothesized second process, which is characterized by parasite spread into new areas through movements of livestock vector. Continuing civil conflict near and within these areas is of particular concern. Once established in new regions, processes of transmission may change from introduction of parasites through cattle movements (process B) into proliferation and continued transmission through increased vector-human exposure resulting from effects of civil conflict (process A). The observed historical trends in sleeping sickness, in the context of our hypotheses, support the likelihood of continued spread of T. b. rhodesiense north from newly infected regions in central Uganda.
The description and characterization of historical reemergence of sleeping sickness in southeastern Uganda can be used to guide and complement research into the causal processes determining the observed patterns of incidence and spread. These patterns are consistent with our hypotheses of 2 dominant processes of sleeping sickness transmission in southeastern Uganda. First, in regions where disease currently occurs or has recently occurred, localized outbreaks are triggered by changes in vector-human exposure or vector numbers, which push the probability of transmission above threshold levels. This process was observed around the traditional infection zone in southeastern Uganda during the 1976–1990 epidemic. Second, in regions where disease has not recently occurred, spread is facilitated by transmission of the parasite thorough livestock. This is currently being observed in the spread of infection to districts in central Uganda that were not infected during the previous epidemic.
Conclusions support further research and intervention related to parasite transmission through cattle movements and potential changes in vector-human exposure in central Ugandan districts. Such analyses are particularly relevant in the context of continued spread of T. b. rhodesiense sleeping sickness in Uganda, potential merging with T. b. gambiense subspecies in northwest regions (24), and ongoing civil unrest in north-central regions.
Acknowledgments
We thank Lance Waller for providing the R-code used for trend surface analysis; Dawson Mbulamberi, Martin Odiit, and Faustine Maiso for data and research support; the late Thomas Gitau for contribution to early research development; and James Ford for manuscript review.
This work was supported by a grant from the International Development Research Centre, Ottawa, Canada, and by the National Science and Engineering Research Council of Canada.
Ms Lea Berrang-Ford is completing a doctoral degree at the University of Guelph and working as a consultant to the Public Health Agency of Canada. Her research interests include use of spatial analyses and systems approaches to address human and environmental health problems.
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University of Veterinary Medicine, Hannover, Germany
Makerere University, Kampala, Uganda
International Livestock Research Institute, Nairobi, Kenya
Sleeping sickness reemerged in southeastern Uganda in the 1970s and remains a public health problem. It has continued to spread north into new districts, and gaps remain in the understanding of the causes of its spread and distribution. We report the distribution and magnitude of sleeping sickness in southeastern Uganda from 1970 to 2003. Data were collected from records of the Ugandan Ministry of Health, individual sleeping sickness treatment centers, and interviews with public health officials. Data were used to develop incidence maps over time, conduct space-time cluster detection analyses, and develop a velocity vector map to visualize spread of sleeping sickness over time in southeastern Uganda. Results show rapid propagation of sleeping sickness from its epicenter in southern Iganga District and its spread north into new districts and foci.
Sleeping sickness is the human form of African trypanosomiasis (caused by Trypanosoma spp.), a protozoal parasitic disease affecting humans, livestock, and many sylvatic species in sub-Saharan Africa. It is transmitted by the tsetse fly vector (Glossina spp.) and in cattle is a serious constraint to livestock development in sub-Saharan Africa (1–3).
The acute form of sleeping sickness, which is caused by Trypanosoma brucei rhodesiense and is predominant in eastern and southern Africa (4–6), is present in southeastern Uganda . Sleeping sickness is a serious public health problem in this region; epidemics have occurred in 1901–1915, 1940–1946, and 1976–1989 (3). More recently, spread of sleeping sickness into areas previously thought to be free from the disease has highlighted gaps in the ability of current research to explain and predict the distribution of infection (7).
In 1976, an outbreak was detected in Luuka County in western Iganga District, outside the traditional fly zone. This was the beginning of an extensive epidemic that eventually spread throughout southeastern Uganda. This outbreak occurred during a time of great political instability and civil conflict in Uganda, which contributed to a reduction of resources and services for sleeping sickness (8). Although the incidence of sleeping sickness decreased in southeastern Uganda in the early 1990s, it continues to persist and spread in 2005. An outbreak was detected for the first time in Soroti District in 1998 (7), followed by continued spread north into Kumi, Kaberamaido, and Lira Districts (9,10). Historical analyses of sleeping sickness in southeastern Uganda can improve disease control by increasing understanding of the context and trends of the disease, as well as identifying variables associated with these trends. Additionally, historical analyses may validate hypothesized processes.
We describe and characterize the spatial distribution of T. b. rhodesiense sleeping sickness in southeastern Uganda for a 34-year epidemic period (1970–2003). We hypothesize that sleeping sickness in southeastern Uganda is driven by 2 dominant processes. In process A, in regions where disease occurs or has recently occurred, localized outbreaks are triggered by processes that increase tsetse populations or by changes that increase human-tsetse contact. In process B, in regions where disease has not recently occurred, spread is facilitated by movement of infected livestock into uninfected regions.
Methods
Study Area
The study area in southeast Uganda in eastern Africa is subdivided into 17 districts, 46 counties, and 254 subcounties. The region has an area of ≈55,000 km2 and a population of ≈9 million (11). Thirteen percent live in the capital of Kampala (11), and the remainder live in predominantly rural areas dominated by livestock and subsistence farming (12,13).
Data Collection
Cross-sectional sleeping sickness data from 1970 to 2003 were collected retrospectively in 2004 to identify case counts and measures of disease magnitude per subcounty per year. Data were collected for all available records of sleeping sickness patients in southeastern Uganda. Data availability and reliability varied between years on the basis of quality of surveillance and primary data collection, as well as availability of records and recall bias for secondary data collection. Reliability of data for 1986 to 2003 was considered moderate to high, but reliability of data for 1970 to 1986 was low to moderate. Evaluation and review of data by public health officials concluded that information on disease prevalence and absence was reliable for most years, but measures of disease magnitude were less reliable before 1986.
Since 1999, sleeping sickness data summaries have been provided by the National Sleeping Sickness Control Program at the Ugandan Ministry of Health. For data before 1988, no centralized collection of records exists beyond district summaries; sleeping sickness case data remain in records at individual treatment centers. Data before 1988 were collected retrospectively in 2004 during visits to all treatment centers active in the 1980s. In many cases, record books were poorly stored, damaged, had lost pages, or were missing . Case definition was based on the primary diagnosis; all cases recorded in record books were included in this study. Cases were assigned to a year based on the patient's date of admission.
Gaps in the dataset increased before 1986. Limited data were available for the late 1970s, and no quantitative data were available for the early- to mid-1970s. Interviews were conducted with public health officials to complement and extend 1970s and 1980s data. These officials were chosen by identifying Ugandans actively involved in senior positions in sleeping sickness prevention and control from 1970 to the present and those who could be contacted. They included veterinary and public health managers at the National Ministry of Health or District Medical or Veterinary Office levels. Interviews were used to verify data for the 1980s and to classify disease magnitude for the 1970s.
Sleeping sickness magnitude was classified into 1 of 5 categories for each subcounty for each year: 1) no cases, 2) preepidemic (1–4 cases per year per subcounty), 3) low epidemic (5–15 cases per year per subcounty), 4) high epidemic (16–100 cases per year per subcounty), and 5) extreme epidemic (>100 cases per year per subcounty). These thresholds were based on anecdotal guidance from preliminary interviews and defined to facilitate standardized definitions of magnitude during subsequent interviews. Interviewer information was compared to available sleeping sickness records and the literature. These results were used to develop a classification database of disease magnitude by subcounty and year. Resulting data and maps were presented to informants for discussion and validation at follow-up interviews in 2005.
The boundaries of political regions changed greatly during the 34-year study period. Aggregation of subcounty data reduced the number of subcounties from 254 in 2004 to 225 for the current study period. Temporal resolution of data is consistent, and aggregation of 29 subcounties is assumed to have little effect on overall analyses.
Data Analysis
Case counts from 225 subcounties in southeastern Uganda for 34 years (1970–2003) were aggregated into 5 temporal periods for descriptive and geographic cluster analysis on the basis of epidemic progression and data availability: 1970–1975, preepidemic; 1976–1979, epidemic increase; 1980–1888, epidemic peak; 1989–1997, epidemic decrease; and 1998–2003, epidemic tail. Mean case counts per subcounty per year were calculated for periods in which case counts were available (1980–1988, 1989–1997, and 1998–2003). For earlier periods (1970–1975 and 1976–1979), only ordinal data were available. Therefore, data midpoints were calculated by using the mean of the maximum and minimum ordinal values rounded to the nearest whole number in the direction of the mode. These data were used to develop maps averaging the annual incidences of sleeping sickness for each subcounty during the interval period. Averages of annual incidence for intervals after 1980 were reclassified as sporadic (<5 cases/year), low epidemic (5–15 cases/year), or high epidemic (>15 cases/year) to match ordinal data categories for 1970s data.
To identify clusters of sleeping sickness in southeastern Uganda from 1970 to 2003, the space-time scan statistic (14) was used (SaTScan version 5.1 software for spatial and space-time scan statistics available from http://www.satscan.org/ [Kulldorff, Boston, MA, USA and Information Management Services Inc., Silver Springs, MD, USA]). The incidence proportions of the 225 subcounties were assumed to follow a Poisson distribution according to the underlying population size. Cluster analysis results include space-time clusters with no geographic overlap of clusters allowed and a maximum allowable cluster size of 50% of the population. Space-only and time-only clusters were excluded. Primary and secondary clusters at a significance level of α = 5% are reported.
Sleeping sickness data were used in the form of case counts per year per subcounty for post-1980 records. For 1970s data, recorded values represent ordinal data (i.e., low, medium, high) rather than case counts. These were transformed to case counts by applying the ordinal minimum value to each record. Population data are based on the 1980, 1991, and 2002 population censuses for Uganda (11). The first 3 analysis periods (1970–1988) used 1980 census records for population counts. Analyses for the periods 1989–1997 and 1998–2003 are based on 1991 and 2002 census records, respectively.
A vector velocity map (15) of sleeping sickness spread was developed by using trend surface analysis (TSA) (16,17). TSA is a global smoothing method using polynomials in geographic coordinates, as defined by the central point of each subcounty polygon. In this case, a trend surface of the year of the first reported sleeping sickness case for each subcounty was used to explore and identify diffusion patterns and corridors of spread over time.
The year of the first recorded case was identified for subcounties in the database. Eighty-nine of 225 subcounties with no recorded cases in the 1970–2003 study period were excluded. The x- and y-coordinates of subcounty centroids were calculated from a UTM projection shapefile of southeastern Uganda using ArcMAP (ArcGIS 9, Environmental Systems Research Institute, Redlands, CA, USA). Least square regression using linear, quadratic, cubic, and higher-order polynomials of the x- and y-coordinates to predict year of first reported case was conducted in R (Foundation for Statistical Computing, Vienna, Austria, available from http://www.R-project.org). Partial differential equations (Δyear/ΔX and Δyear/ΔY) were derived from the fitted model, giving a vector of the magnitude (slope) and direction for each location. The square root of the slope equates to the velocity of diffusion.
Results
Epidemic Curve
Incidence Maps and Cluster Detection
1970–1975: Preepidemic
1976–1979: Epidemic Increase
1980–1988: Epidemic Peak
1989–1997: Epidemic Decrease
1998–2003: Epidemic Tail
Trend Surface Analysis
The results from trend surface analysis are summarized in a velocity vector map (Figure 9). The velocity and direction of diffusion for each coordinate location were mapped to show the movement and instantaneous rate of T. b. rhodesiense sleeping sickness diffusion in southeastern Uganda over the study period. TSA with high-order polynomials is sensitive to data anomalies at the edge of the study area (15). Less data are available at the study area boundaries; velocity vector size and direction are therefore less reliable and may not be accurate at the edge of the study area. For these reasons, 9 velocity vectors were removed from the vector diffusion map (Figure 9).
The average velocity of sleeping sickness spread over 34 years in southeastern Uganda from 1970 to 2003 was 5 km/year. Velocity of movement was highest early in the epidemic (Figure 9), when sleeping sickness spread out of its primary focus in southern Iganga District. The epidemic diffused outward in a relatively constant sphere of diffusion from this epicenter. A corridor of movement can be observed on the eastern fringe of the study area, moving through Busia and Tororo Districts. However, this fringe area should be interpreted with caution because of potential edge effects. The disease moved distinctly north and east into Soroti District. Areas of most rapid spread appear to be the extensions of these 2 corridors north from Soroti and Tororo. These results are consistent with recent detection of cases in the districts of Kumi, Kaberamaido, and Lira (9,10) adjacent to or north of Soroti. Velocity vectors also showed spread west and east. However, Figures 4–8 suggest that much of this horizontal diffusion occurred before the 1990s.
Discussion
The reliability of data for the 1970s and 1980s is subject to detection and recording bias associated with periods of passive surveillance, missing record books, and recall bias of interviewees. The creation of additional treatment centers over the study period and differential quality of diagnostic and treatment facilities throughout the study area may contribute to spatial bias in the data. Odiit et al. (20–22) discuss the potential for misdiagnosis of cases, selective entry bias around treatment centers, and underdetection of sleeping sickness. Aggregation of cases by subcounty reduces the potential for clustering around individual treatment centers, and unless differential misdiagnosis occurs, it will not critically affect the spatial patterns seen. The data must be interpreted with caution in the context of data reliability and potential biases. Results should be considered exploratory and descriptive; data are not appropriate for direct causal inferences. The results are, however, useful for characterizing broad trends; where historical trends in processes observed are consistent with hypotheses, results can inform current and future research.
T. b. rhodesiense sleeping sickness in southeastern Uganda from 1970 to 2003 followed a pattern of radial spread from its center in southern Iganga District. From 1976 to the 1990s (Figures 4–7), the epidemic trend coincided with civil unrest and political instability in the country. The increase in the epidemic (1976–1979) occurred at a time of increasing political and economic instability, while the peak epidemic period (1980–1988) occurred during the height of political and economic collapse. The decrease in the epidemic (1989–1997) also coincides with increasing stabilization of politics and civil unrest in Uganda. The epidemic trend observed is consistent with our hypothesis (process A) that incidence increases in regions with a history of infection because of changes in human-vector exposure that push the probability of transmission above the required threshold for focal outbreaks. Uganda in the 1970s and 1980s experienced extensive internal displacement of the rural population, illegal human and cattle movements, growth of favorable tsetse habitats on cotton and coffee plantations, and collapse of sleeping sickness prevention and control activities (8,19,23). These events likely contributed to increased human-vector contact and sleeping sickness transmission in the districts around the preepidemic zone of infection.
After the decrease in the epidemic in the 1990s, new outbreaks have been observed in Soroti (1998, Figure 8), Kaberamaido, Kumi, and Lira (2004–2005) Districts (7,9,10). The introduction of the parasite into Soroti District has been linked to cattle restocking from infected southern districts (7). Whether more recent spread into new districts is related to cattle movements is unclear. Postepidemic spread into previously uninfected and peripheral districts since the late 1990s is consistent with our hypothesized second process, which is characterized by parasite spread into new areas through movements of livestock vector. Continuing civil conflict near and within these areas is of particular concern. Once established in new regions, processes of transmission may change from introduction of parasites through cattle movements (process B) into proliferation and continued transmission through increased vector-human exposure resulting from effects of civil conflict (process A). The observed historical trends in sleeping sickness, in the context of our hypotheses, support the likelihood of continued spread of T. b. rhodesiense north from newly infected regions in central Uganda.
The description and characterization of historical reemergence of sleeping sickness in southeastern Uganda can be used to guide and complement research into the causal processes determining the observed patterns of incidence and spread. These patterns are consistent with our hypotheses of 2 dominant processes of sleeping sickness transmission in southeastern Uganda. First, in regions where disease currently occurs or has recently occurred, localized outbreaks are triggered by changes in vector-human exposure or vector numbers, which push the probability of transmission above threshold levels. This process was observed around the traditional infection zone in southeastern Uganda during the 1976–1990 epidemic. Second, in regions where disease has not recently occurred, spread is facilitated by transmission of the parasite thorough livestock. This is currently being observed in the spread of infection to districts in central Uganda that were not infected during the previous epidemic.
Conclusions support further research and intervention related to parasite transmission through cattle movements and potential changes in vector-human exposure in central Ugandan districts. Such analyses are particularly relevant in the context of continued spread of T. b. rhodesiense sleeping sickness in Uganda, potential merging with T. b. gambiense subspecies in northwest regions (24), and ongoing civil unrest in north-central regions.
Acknowledgments
We thank Lance Waller for providing the R-code used for trend surface analysis; Dawson Mbulamberi, Martin Odiit, and Faustine Maiso for data and research support; the late Thomas Gitau for contribution to early research development; and James Ford for manuscript review.
This work was supported by a grant from the International Development Research Centre, Ottawa, Canada, and by the National Science and Engineering Research Council of Canada.
Ms Lea Berrang-Ford is completing a doctoral degree at the University of Guelph and working as a consultant to the Public Health Agency of Canada. Her research interests include use of spatial analyses and systems approaches to address human and environmental health problems.
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