Background
Sleeping sickness, so called Human African Trypanosomiasis (HAT) is a parasitic vector-borne disease caused by the genus Trypanosoma (T.) and species
brucei [
1]. The disease is transmitted to humans by the bite of an infected both female and male tsetse fly (
Glossina species) [
2], hematophagous and, capable of transmitting infection [
3].
T. b. rhodesiense is one of the HAT subspecies found in eastern and southern Africa, causing an acute and rapidly progressive disease [
4].
Rhodesiense is another subspecies of HAT that has epidemic potential in humans, as it has been responsible for large outbreaks in the past decade [
5]. The
Trypanosoma genus are also pathogenic to animals (both in wild and domestic) and cause African trypanosomiasis (AAT), called
Nagana [
6]. The spread out of parasites from wildlife to domestic livestock and humans, and from domestic animal species to wildlife, compromises health [
7]. Most trypanosome infections in wildlife do not cause apparent harm to their hosts, but some wildlife species are extremely at risk to trypanosome infections [
8]
. T. b. rhodesiense, can be found in both domestic and wild animals, contract
T. b. gambiense and most likely serve as reservoirs [
9]. However, it is still unclear how exactly the animal reservoir contributes to the epidemiology of the disease of the
gambiense type.
T. brucei,
T. congolense,
T. simiae, and
T. uniforme are transmitted within the tsetse belts of Africa. Within and outside tsetse fly-infested zones
, T. vivax and
T. evansi can be transmitted mechanically[
10]. Sleeping sickness threatens millions of people in 36 sub-Saharan Africa living in remote rural areas with limited access to adequate health services [
11]. This complicates the surveillance and, therefore, the diagnosis and treatment of cases is neglected. Additionally, factors like population displacement, war, and poverty are facilitating the transmission. HAT, without distinction between
T. b. gambiense and
T. b. rhodesiense, was considered in the first Global Burden of Disease assessments and estimated to result in 1.78 million DALYs lost across Africa and the good reason for numerous of the parameters pertaining to HAT and used in the global assessments (e.g., disability weighting, and estimates of incidence) is not transparent and is a major problem
. [
12].
Currently, in Africa, animal Trypanosoma species such as
T. congolense (found in tsetse-infested areas),
T. viva x (found in both tsetse-infested and tsetse-free areas except in the highlands >2500 m above sea level)
, and
T. brucei are commonly known.
T. evansi (surra) and
T. equiperdum can occur in tsetse-free areas [
13]. The transmission of Trypanosoma
vivax is cyclical (transmitted by the tsetse fly) and mechanical (by
tabanidae and
stomoxys).
T. evansi in camels and
T. equiperdum in horses are transmitted by the tsetse fly, Stomoxys and Tabanus, but mechanical transmission to domestic animals [
14].
Cattle movement is a threat for the disease transmission, spread, and occurrences of outbreaks [
14]. Wildlife hosts: bushbucks (
Tragelaphusscriptus), impalas (
Aepycerosmelampus), lions (
Pantheraleo), zebras (
Equus quagga boehma), warthogs (
Phacocoerusafricanus), and duikers (
Sylvicapragrimmia) carry the human-infective zoonotic trypanosome strain
T. b. rhodesiense [
13]. People can be bitten by an infective tsetse fly while farming, fishing, hunting, collecting water or wood, or engaging in any other activity. More focus is needed on Tsetse fly or vector control (bush clearing, game animal elimination, and ground and aerial spray) [
3]. Insecticide Treated Cattle (1% Deltamethrin pour on Animal),
deltamethrin 1% pour-on on domestic animals to prevent the animals from insect bites and to act like mobile targets [
15]
. Blue -Black-Blue target impregnated with insecticides and deployed in tsetse-infested areas
by using deltamethrin 20% impregnated targets and ground spray have been used [
16]
. A ground spray in areas where targets are difficult to deploy [
17] and SIT is a very specific method to the target species, non-pollutant, more effective, and has no adverse effect on other living organisms [
18]. Barrier Establishment avoid the dangers of re-invasion, effort should be made to close the possible reinvasion site with artificial barriers (using traps and stationary targets) [
19].
AAT is also a major constraint to the development of the livestock sector, and induces a decrease of livestock productivity. Tsetse flies are the main vectors of both HAT and AAT, a major factor in trypanosomiasis epidemiology by their central role in transmission of trypanosoma to vertebrate hosts [
20]. In Ethiopia, animal trypanosomiasis is a significant obstruction to livestock and farm production [
21] with approximately 75% of the area favorable for the proliferation of tsetse flies in the southern nation's nationalities and people's region states (SNNPR). And also Trypanosomiasis is prevalent in two main regions of Ethiopia: the northwest and the southwest [
8]. Most of the areas in Gamo and Gofa zones in the region are suitable (with their savannah-covered national parks, river basins, ambient temperature, and bushy land nature) for tsetse multiplication [
22]. In 1967, a confirmed HAT case was reported for the first in Ethiopia. The distribution of endemic human trypanosomiasis and its tsetse vectors appears to be limited to southern and southwestern Ethiopia (Oromia Region (Illubabor and Wollega), Gambella, and SNNPR). No major outbreak of the disease was recorded until the 1969-1970 epidemics and then after, only sporadic cases have been reported [
23].
Currently, in August 2022, the SNNP Regional Health Bureau has reported 5 cases of HAT from Kucha Alpha woreda, Gamo zone, to the ministry of health Ethiopia. Dried blood spot samples were collected and transported to the Institute of Tropical Medicine, Antwerp, Belgium, through DHL and confirmed to be
T. b. rhodesiense. HAT reoccurrence is linked to absence of surveillance system, the presence of favorable ecology for vector distribution and disease transmission, the presence of agricultural activities in proximity to vector habitat and the presence of reservoir wild animals in proximity with the human residence, the absence of road accessibility for controlling activities and lack of collaboration (one health). The epidemiology of HAT in Ethiopia remains unclear and will be essential to clarify in order to develop more effective and accessible diagnostic, treatment and control programs. Analyzing HAT data by place of infection on a longitudinal basis would provide valuable data on local risk and transmission characteristics and indicate whether control programs were effective. Without an accurate picture of the true epidemiology of HAT in Ethiopia, associations with environmental, vector, animal, and human factors cannot be analyzed and used to inform policy [
24].
Identification of trypanosomes in tsetse flies and reservoir hosts could be a good indicator for HAT and AAT within an area [
25]. Detection of pathogenic trypanosomes in animals and identification of tsetse flies and their distribution status within different environmental variables will highlight the areas at risk [20, 26]. Such type of information will help in the use of adapted control methods in this increasingly anthropized habitat within vector human activity overlap. Thus, the current investigation was initiated to identify the root cause of HAT reemergence in Ethiopia after 55 years.
Discussion
Cases of HAT were confirmed by parasitological testing after active medical work-up and five cases were confirmed in these areas after 55 years of HAT occurrence in 1967 in Ethiopia. Among all five cases four deaths were recorded. The attack rate (AR) and case fatality rate (CFR) of the human African trypanosomiasis were between 37 and 38 and 80% respectively in the study population, with the majority of patients being male (15 – 44 years old). In Africa, approximately, 70 million people (1.55 million km
2) are estimated to be at risk of HAT and this corresponds to 10% of the total population and 7.4% of the total area of the endemic countries [
37]. It was reported that HAT infected children rate is generally less than that observed in adults because of their lower exposure to flies during daily activities except those children who often accompany their parents during any activities [
38]. As in outbreak areas of the Southwestern Ethiopia, sleeping sickness in Kucha Alpha and Demba Gofa is a rural disease mainly affecting the working population and productivity (farmer). Almost all patients in our study areas were from the native population that is self-employed (from farming households) and lives in villages with no immigrant population. The study reports from the Republic of Congo confirmed that uneducated participants as well as those aged more than 15 years were significantly at high risk of HAT infection compared to their corresponding person [
38]. The majority of the positive cases were from households working in farming (animal and agricultural farming) [
39]. All age groups and both sexes are at risk, the prevalence is higher in adults and the sex distribution varies in relation to gender-specific at-risk activities (e.g., mainly male hunting and fishing or principally female water fetching and small crop growing) [
40].
This finding could provide a useful diagnostic sign for screening populations living in these Mazie forest regions and as a source for parasitological diagnosis and establishing better control programs. So the main objective of the current study was to screen the population at risk and risk factors and provide information on human African trypanosomiasis transmission in outbreak areas Kucha Alpha (Gamo Zone) and Demba Gofa (Gofa Zone) of Ethiopia. The findings of this study emphasize the call for not only to go on surveillance in these regions but also to expand surveillance throughout the country as a means of avoiding reemergence and spread of the disease.
In the current study areas, high-risk factors that predispose the community to Human African Trypanosomiasis (HAT) were identified in the HAT outbreak investigation areas. Cropping is considered to play a major role in maintaining HAT reemergence. This risk zone is in association with the Maze National Park and the Omo and Gibe River. There was a high movement of cattle and people to the Omo River for castling and fetching water, where the favorable environment for the breeding of tsetse flies vectors
with high density. At the areas limit of trypanosomiasis distribution, nature reserves shape the patterns of HAT risk [
37], most notably in around near the developmental corridor, cattle farming and agricultural intensification within the natural parks and Forest of Omo River and gibe catchment in agreement with the Geo-referenced layers of sleeping sickness occurrence and human population for the period 2000–2009 [
37].
In this study, entomological investigation was conducted to improve our knowledge on the distribution of trypanosomes responsible for HAT and AAT. The tsetse flies were caught and dissected along the outbreak areas revealed that two species of Glossina (
G. pallidipes and
G. fuscipes) were found to be the predominant species. The presence of these two different species of Tsetse flies around where HAT cases were reported, areas implied that the disease is infecting the communities from animal reservoirs. It is likely that the identified Tsetse fly species are feeding on both small and large wild and domestic animals to facilitate the transmission of the HAT [
41]. The findings in the present study corroborate entomological and epizootic information from the national atlas of tsetse flies and animal trypanosomosis in Ethiopia. In particular, our study confirms that in the study zone two species of tsetse flies occur (i.e.
G. pallidipes and
G. fuscipes), and that
T. vivax and
T. congolense are the dominant species of trypanosomes circulating in cattle [
42]. The overall apparent density of tsetse fly was found to be very much high (AD = 164.5) per trap per day which is in contrast to the study reported that less AD of tsetse fly was recorded in Benishangul Gumuz in Ethiopia [
43]. As in the AD of species comparison of previous study,
G. pallidipes abundance in the current study area is higher than the previous study in Jima by Lemu
et al. [
34]. This higher abundance of tsetse species might be linked to suitable vegetation and available host density [
44] and differences in agro ecology [
34] and bioclimatic conditions during the trapping periods. The pathogenic trypanosomes identification in tsetse flies has helped to highlight human and animal trypanosomiasis associated with different biotopes (ecology) potential risks [
26]. In the current study findings, the densities of the tsetse flies were also high in wood land, relatively less in bush land and grassland. This may be due to a combination of factors including favorable climatic conditions for the survival and dispersal ability of this species and abundant vegetation attracting hosts [
20]. The current finding is in agreement with the study report from BenishangulGumuz region of Ethiopia by Mekonen
et al. [
43]who stated that the vegetation is vital for providing suitable conditions; the savanna, forest and riverine tsetse flies concentrate in the wooden savanna, in the bush vegetation and near the edge of the river, where the vegetation is dense.
High numbers of flies were observed unfed in the current study areas. This may impact the parasite density within the tsetse fly population and trypanosomiasis transmission. This may be an important factor in natural situations where densities of hosts commonly fed on by tsetse, can vary between periods [
45]. Host population movement can determine the feeding status of the vectors. Moreover, as one moves from protected areas into farmland, host densities may drop below those required for sustaining tsetse populations but increasing host densities in others areas [
46]. Similarly, wild and domestic host’s densities are essential factors for trypanosome transmission, affecting vector density, and mortality rates. The existence of hungrier flies in regions where wild hosts are scarce can have implications for trypanosome transmission. First hungrier flies may be more likely to bite less preferential hosts, including humans, thereby ever-increasing the trypanosomiasis transmission risk [
47].
None of dissected tsetse fly species were positive for HAT parasite. The absence of infected salivary glands in the present study confirms that the natural infection rate of tsetse by trypanosomes of
brucei complex remains very low in agreement with study report by Vincent et al. [
20] in Cote D'ivoire. The absence of infected tsetse flies in HAT case reported areas could not be guaranteed for the absences of future infection in the area, similarly, zero prevalence most probably would not mean any parasite infected tsetse flies were present in the area [
45,
48].
The overall prevalence of Trypanosomiasis in animals was 3% (
T. congolense 6 (2%) and
T. vivax 1 (0.3%)) with 2 (0.7%) suspected
brucei in the investigated areas. The presence of
T. congolense and
T. vivax is an indicator of AAT transmission magnitude near the Maze National Park in agreement to other studies [
49]. The prevalence of bovine trypanosomosis in the present study areas was significantly lower than the previous study reports [
43]. This suggests that livestock expansion will be seriously hampered by the Nagana if control measures against tsetse flies and trypanosomes are not taken prior to cattle introduction along with this river and park [
43]. This study result showed that risk prevalence of trypanosomosis was high in poor body conditions (Bcs) cattle compared the other body conditions )medium and good) which indicates that infection rates in poor body condition animals were significantly higher than that of medium and good body condition animals. This is due to poor body condition, animals are at risk of the infectious disease, reduced animal presentation created by lack of essential nutrients and poor management [
34].
There are several weaknesses in the current study design, which need to be considered when interpreting the findings of the current study report. Moreover, the current study has not covered large geographical areas within short data collection periods to diversify the species and get positive tsetse flies. As this study was employed to use only three collection techniques, it would not have been appropriate to collect a high number of blood-fed mosquitoes for blood meal origin analysis and seasonal variation data was not included.
Author Contributions
AW: Conceptualization, Methodology, Resource, Investigation, Visualization, Validation, Data curation, Formal analysis, wrote the main manuscript (Writing-original draft, and Writing-review and editing). EA: AG, HT, BM, MH, HD, AE, AK, GG, TW, NM, TH, KK, NA, JH, WM, DT, AA, BB, FL, TM, FT, KA, TM, YM, MW and FR: Conceptualization, Methodology, Visualization, Validation, Formal analysis and Writing-review and editing, Methodology, Visualization, Validation, Formal analysis, Writing-original draft and Writing-review and editing. GT and AA: Supervision, Visualization, Validation, Formal analysis, Writing-review, and editing. All authors have read and agreed to the published version of the manuscript. All authors have read and agreed to the published version of the manuscript.