Progress in Human African Trypanosomiasis, Sleeping Sickness
Book file PDF easily for everyone and every device.
You can download and read online Progress in Human African Trypanosomiasis, Sleeping Sickness file PDF Book only if you are registered here.
And also you can download or read online all Book PDF file that related with Progress in Human African Trypanosomiasis, Sleeping Sickness book.
Happy reading Progress in Human African Trypanosomiasis, Sleeping Sickness Bookeveryone.
Download file Free Book PDF Progress in Human African Trypanosomiasis, Sleeping Sickness at Complete PDF Library.
This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats.
Here is The CompletePDF Book Library.
It's free to register here to get Book file PDF Progress in Human African Trypanosomiasis, Sleeping Sickness Pocket Guide.
The network strengthens collaboration and supports national programmes by leading and coordinating the actions of all stakeholders in each endemic country. Strategic advances in monitoring, evaluation and data management have also been seen. WHO has introduced new indicators and has trained national data managers, resulting in better information on populations and areas at risk and on access to diagnosis and treatment. This will help the programme to target surveillance and interventions. Programmes should nevertheless use vector control to supplement case detection and treatment as part of the elimination strategy.
Furthermore, programme expertise should be made available to country health systems, including peripheral health centres, to prevent the disease from reappearing after elimination. The results of research on a new oral treatment are anxiously awaited, as there are serious problems with current therapy, which requires intravenous infusion by skilled personnel. These various elements contribute to immunosuppression. Trypanosomes have learnt to use immune mechanisms to its own profit. Recent data show the importance of alternative macrophage activation, including arginase induction.
L-ornithine produced by host arginase is essential to parasite growth. All these data reflect the deep insight into the immune system realised by trypanosomes and might suggest interference therapeutic approaches. Key words: Trypanosome, African trypanosomiasis, immunology, macrophage, lymphocytes, nitric oxide, cytokine, autoantibodies.
O IFN- g atua como um fator de crescimento do parasita. Sleeping sickness or human African trypanosomiasis HAT is an endemic parasitic disease exclusively located in intertropical Africa where it is transmitted by the tsetse fly or Glossina , its unique vector Vickerman The new taxonomy tools used in African trypanosomes isoenzyme characterisation, DNA analysis have allowed scientists to separate the Trypanosoma brucei clade in several subspecies.
Two are infective for humans: T. These extracellular parasites are injected into humans by the bite of infected tsetse fly.. The inoculation of trypanosomes into their mammalian hosts triggers a series of events involving, at first, innate immunity and, secondarily, specific immunity. The latter requires an efficient presentation of parasitic antigens, activation of T and B cells implying specific antigen receptor recognition, and the development of effector cells and molecules. These mechanisms are highly regulated by multiple signals delivered through a large number of receptors transduced across the plasma membrane and processed.
During co-evolution with their hosts, trypanosomes have learnt to cope with host immune systems, by penetrating, diverting, and altering the numerous steps leading to the generation of an effective immune response. Major modifications of immune systems have been observed in trypanosomiasis: lymphadenopathy, splenomegaly up to thirty times the normal size with destruction of lymphatic tissue architecture and hypergammaglobulinemia. However, their effectiveness is limited as, most of the time, parasites cannot be eliminated and immunopathological phenomena, which induce tissular alterations, appear.
One of the major characteristics of trypanosomes is the presence of the Variant Surface Glycoprotein VSG which covers nearly all the membrane of trypanosomes in mammals and is the predominant surface antigen of African trypanosomes. VSG constitutes an important molecular interface between trypanosomes and the host immune system Figure 1.
VSG prevents trypanosome lysis by complement alternative pathway, and, above all, enables them to avoid the specific immune response via the phenomenon of antigenic variation trypanosomes sequentially express antigenically distinct VSG.
VSG also has several effects on immune elements such as induction of autoantibodies and cytokines, in particular tumour necrosis factor TNF - a Tachado and Schofield , Okomo-Assoumou et al. Other trypanosome components and soluble factors, such as a trypanosome-released triggering factor TLTF which triggers interferon IFN - g production by T cells, are also involved in modulation of the immune system by acting on the synthesis of immune elements Olsson et al. Furthermore, increased levels of circulating endotoxins are a feature of human and experimental trypanosomiasis.
These endotoxins, potent immunomodulatory molecules, participate to the immune disorders observed in trypanosomiasis. Nyakundi et al. Elaboration of escape mechanisms to host immune defences and induction of parasite growth factor production are well developed by trypanosomes. In a recently discovered escape mechanism, host arginase induction, trypanosomes decrease immune response efficiency and increase the production of L-ornithine, an essential growth factor Gobert et al. Understanding of the immune response was recently advanced by the discovery of the T and B subpopulations and, especially, of the T helper Th subsets, as well as the cytokines synthesised by each Th1 and Th2 subset.
Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?
These factors control different aspects of the immune response, in peculiar the synthesis of nitric oxide, which is probably involved in several steps in the immune mechanisms. The role of gd T cells should also be taken into account as they have been implicated in other parasitic diseases such as malaria and leishmaniasis. Most of the data concerning African trypanosomiasis have been obtained in animal diseases or experimental animal models.
Few studies haveconcentrated only on the immunology of HAT. Results obtained from animal diseasesor experimental models can be investigated in human trypanosomiasis using adapted means. Genetic analysis of resistance and susceptibility to infection in inbred and congenic animal strains form the basis for research into equivalent genes in humans. The recent knowledge of the entire genome of T. After a painful tsetse bite, the chancre from several millimetres to centimetres represents the initial lesion at the bite site, characterised by local erythema, oedema, heat, tenderness and a lack of any suppuration.
Trypanosomes are present in the inflammatory tissues. The chancre disappears within 2 or 3 weeks. The disease evolves in two distinct successive phases determining its two pathological stages Molyneux et al. Within a few days after the tsetse bite, the patient enters the haemolymphatic stage I of the illness. Clinical signs appear very early. Intermittent fever develops as a consequence of the successive waves of invasion of the blood by the trypanosomes. Adenopathies, splenomegaly, or even hepatological signs mark the invasion of the reticulo-endothelial system.
Skin eruptions or trypanides are commonly observed. Severe pruritus with scratching skin lesions becomes unsupportable for the patient. Cardiovascular alterations are less prominent, especially in the Gambian form. Irregular febrile episodes are accompanied by headaches, malaise, exhaustion, anorexia, extreme thirst, muscle and joint pains, pruritus, anaemia, rash and often deep hyperesthesia the sign of the key of Kerandel. The lymph nodes are generally rubbery and mobile,painful at the beginning.
Palpation of the subclavicular region Winterbottom sign is an important part of the diagnostic procedure in the Gambian form. Any adenopathy accompanied by fever should evoke the diagnosis of sleeping sickness in patients from endemic areas. Later, pruritus generalises.
Oedema of the face and extremities appears early. Few minor neurological and endocrine disorders may reveal the precocity of central nervoussystem CNS involvement, long before any detectable changes occur in the cerebrospinal fluid CSF. Daytime somnolence or night-time insomnia may already be reported and electroencephalographic EEG tracings may reveal abnormalities. Psychiatric signs, with the alternation of irritability, changes in personality or mood affecting the daily and professional life of the patients, constitute often the first manifestation of the disease.
The endocrine syndrome is marked by a permanent feeling of coldness, lack of appetite or in contrast hyperphagia, polydipsia and impotence, amenorrhea or infertility, indicative of vegetative and sexual disturbances. The meningoencephalitic stage appears slowlyand insidiously over a period of months or yearsdepending on the trypanosome.
However, the clinical signs remain reversible for a long time withtreatment attesting to the predominance of potentially reversible inflammatory lesions over irreversible demyelinating lesions. The general signs ofthe haemolymphatic stage do not completely disappear: spikes of fever but sometimes hypothermia , adenopathies and splenomegaly, cardiovascular manifestationsendocrine disturbances and typical pruritus.
The development of the neurological symptoms is progressive. As neurological signs occur already in stage I, biological criteria are the only means to confirm CNS invasion. A wide variety of symptoms are encountered. The main symptoms from which sleeping sickness was named are daytime somnolence and nocturnal insomnia, the patients being "sleepy by day and restless by night". The sleep-wake cycle disturbances are accompanied with either or many of the following symptoms: headaches, sensory disturbances with diffuse superficial or deep sensations muscle and bone hyperesthesia, either spontaneous or provoked; hyperpathia , presence of primitive reflexes palm-mental reflex, sucking reflex , exaggerated deep tendon reflexes, psychiatric disorders confusion, mood swings, agitation, aggressive behaviour, euphoria, absent gaze, mutism, indifference , and tremor fine and diffuse without any myoclonic jerk at rest or during movement.
Pyramidal alterations revealed by a Babinski sign can also be observed along with alterations in muscle tone, numbness or sensory deficit. An abnormal number of monocytic cells is observed in the CSF. The early neurological symptoms correlate with the widespread meningeal inflammation, which occurs in both forms of HAT.
BMJ Best Practice
The selective CNS locations explain in part the principal clinical neurological signs. Sleep-wake disturbances may result from invasion of the median eminence by parasites, which also accounts for neuro-endocrine dysfunctions with the involvement ofthe suprachiasmatic nuclei.
- The Upside of Irrationality: The Unexpected Benefits of Defying Logic at Work and at Home.
- The prospect of immortality.
- Monitoring the elimination of human African trypanosomiasis: Update to .
Disorders of the sleep-wake cycle are accompanied by a state of apathy in the patient, the loss of muscle tone especially in the neck muscles and a drooping of the eyelids. Extrapyramidal symptoms signal the involvement of the striatum. Deep sensory disturbances with hyperpathia may result from the involvement of the thalamus and the early invasion of posterior spinal roots. Apart from the disruptions of the circadian rhythm of the sleep-wake cycle, other biological rhythms are disturbed, such as body temperature, cortisol and prolactin or growth hormone secretion.
The invasion of the subthalamic and hypophyseal regions account for the persistence of ad-endocrine disturbances such as impotence, amenorrhea or infertility and the development of disturbed sensations of hunger and thirst, with often hyperphagia and polydipsia in contrast to the poor general state of malnutrition of the patients.
At the terminal phase of the disease, CNS demyelination and atrophy areaccompanied with disturbances in consciousnessand the development of dementia with incoherence, incontinence and epileptic fits. The patient dies in a state of cachexia and physiological misery. The study of inbred and congeneic mouse strains has contributed greatly to our understanding of the genetic regulation of infectious diseases. A number of genes control infections of various pathogens by acting at the level of innate susceptibility, or at the level of acquired immunity. They may or may notbe linked to the major histocompatibility class MHC locus H2.
Inbred strains of mice differ in their susceptibility to infection with T. The existence of inbred susceptible and resistant strains of mice has made it possible to study the inheritance and mechanisms of host resistance. Resistance of mice to African trypanosomes is genetically determined. The control of resistance has been considered as dominant Greenblatt et al. The use of different inbred mouse strains and trypanosome clones may explain this result discrepancy.
However, in T. Three loci influencing resistance of mice to T. African cattle trypanosomiasis, mainly due to T. Some African cattle breeds N'Dama are, however, able to live and be productive in endemic areas and are considered to be trypanotolerant. Trypanotolerance is genetically controlled and is an innate character, but can be increased by repeated infections.
Trypanotolerant cattle are not refractory to trypanosome infections but limit proliferation of trypanosomes. Parasite counts are lower than in trypanosensitive cattle Bos taurus , B. This resistance depends on the nutritional, physiological and stress conditions of the animal. Besides, studies of other factors in relation to host defence and survival, and especially cytokine production, have revealed that the ability to produce. IL-4 plays a role in the susceptibility to T. Recently, mouse strain susceptibility to trypanosome infection has been correlated with an increase in host arginase production Duleu et al.
Little is known about the effect of genetic polymorphism on infectious diseases in humans. Identification of human homologues for the murine genes controlling resistance and susceptibility to pathogens is in progress. Family studies should also be performed. Our knowledge of human trypanotolerance is based on reported cases Lapeyssonnie and results from immunological screening Lemesre et al.
Subjects with a positive CATT card agglutination trypanosomiasis test were asymptomatic whereas the presence of blood parasites was observed. Moreover, although many Bantou people from Mbomo foci in the Congo were infected with T. This effect, present before infection and unrelated to antibody production, is dependent on innate immunity factors.
Normal human sera injected into T. This phenomenon was not reproduced with the human trypanosome strains T. Trypanolytic factors TLF contained in normal human serum were identified as high-density lipoproteins Rifkin Recently, two TLFs have been characterised in human serum. The first one TLF1 belongs to a subclass of high-density lipoproteins and is inhibited by haptoglobin.
In contrast, the second factor, TLF2, has a much higher molecular weight and does not appear to be a lipoprotein. Probably, the main trypanolytic effect is due to TLF2, which is not inhibited by haptoglobin Raper et al. The trypanocidal effect of cape buffalo serum has been attributed to xanthine oxidase Muranjan et al. Recently a trypanosome lysosomal protein SRA was found to be associated with resistanceto normal human serum.
The local response in the skin corresponds to the first protection developed by the host. Following inoculation of T.
- Human African trypanosomiasis progress?
- Progress in Human African Trypanosomiasis, Sleeping Sickness.
- More from News.
- Homosexual Behaviour. Therapy and Assessment?
- Advances in Computational Science and Engineering: Second International Conference, FGCN 2008, Workshops and Symposia, Sanya, Hainan Island, China, December 13-15, 2008 in Computer and Information Science).
In efferent lymphatic vessels, trypanosomes have been detected in lymph days before the chancre. Their number declined during development of the chancre 6 days and later increased. They are detected in the blood 5 days after inoculation. As the chancres regressed there was an increase in lymphoblasts and surface immunoglobulin bearing cells Mwangi et al. During this first stage, trypanosomes expressed Variable Antigen Types VATs found characteristically in the tsetse fly, which changed after few days.
An antibody response specific to these VATs appearedin the lymph and then in the plasma Barry andEmergy Both in humans and animals, complement activation by two pathways is detected in HAT. The alternative pathway, independent of specific antibodies, was studied by the induction of trypanosome lysis T.
Serum could induce trypanosome lysis only on uncoated VSG trypanosomes, as observed during the cycle of this parasite procyclic forms. However, the appearance of VSG on parasites prevents trypanosome lysis by this alternative pathway Ferrante and Allison For another strain of T. The coated stages of T. Nevertheless, during these complement activations, the appearance of soluble fragments, including C3a and C5a anaphylatoxins and the C complex, could induce, on the one hand, the chemotactism of neutrophils and monocytes and, on the other hand, the release of amines involved in vasoconstriction and an increase in vascular permeability participating in the initial inflammatory response in the chancre.
Immune complexes can also activate the complement. These immune complexes are constituted by antibodies specific to trypanosomes e. These immune complexes with complement activation are also involved in some adverse effects, especially in tissue damage mediated by immune complex deposits Nielsen , such as thrombosis and glomerular involvement Bruijn et al. Natural killer NK cells have been identified asan important defence mechanism against tumourcells and intracellular pathogens, especially viruses.
They are considered to belong to the lymphocyte lineage and have functions in both innate and acquired immune responses. NK cells lyse extracellular parasites. NK cells from T. NK cells secrete cytokines and especially IFN- g and TNF- a , which play major roles in trypanosomiasis and are regulated by cytokines which can activate or inhibit NK cell functions.
NK cells also participate in the initiation of the inflammatory response, through the synthesis of chemokines. By contrast, NK cells were activated in mice infected with a natural extracellular trypanosome T. Initial studies have evidenced alterations in T cell functions in trypanosomiasis, both in vivo and in vitro Mansfield and Wallace Figure 2. Histological examination revealed a massive B cellexpansion in the lymph nodes and spleen, which replaced the thymus-dependant area in T. These changes were seen within 7 days post-infection and persisted for at least 70 days. Moreover the role of T cells incontrolling infection was not clear Askonas and Bancroft Trypanosome antigen-specific T cell response was difficult to identify.
In several studies, a transient proliferative T cell response to trypanosome antigens was noted in the first days of the infection followed by an absence of response Gasbarre et al. The kinetoplastid membrane protein 11 of African trypanosomes is a potent stimulatorof T lymphocyte proliferation Tolson et al. However, a strong trypanosome-specific T cell proliferation occurred in infected cattle following treatment Emery et al.
Most T cells in humans and mice bear Tabantigen receptors. The knowledge of T cell subsets has been deeply modified by the discovery of two subsets of T helper cells, Th1 and Th2 cells.
VSG specific T cells were found predominantly in the peritoneum. Analysis of lymphocyte subsets in regionallymph nodes of T. Human and mouse immune systems contain few gd T cells, in marked contrast to those of ruminants Hein and Mac Kay Functions of gd T cells remain largely unknown. Involvement of gd T cells in malaria and leishmaniasis has been observed Rosat et al. The role of this gd T cell response in parasite resistance remains unclear. It would be interesting to determine the role of cytokines synthesised by gd T cells.
Indeed, although specific T cells do not act on trypanosomes in the same way as the cytotoxic T cells in several infectious diseases such as viral infections, they markedly modify immune responses, especially by the secretion of cytokines. They greatly modify functions of B cells antibody synthesis, isotype switch and macrophages antigen presentation, effector mechanisms.
In African trypanosomiasis, the main feature is a dramatic increase in immunoglobulin Ig levels especially IgM , including trypanosome-specificantibodies and non-specific Ig production induced by cytokine activation of B cells. Some of these antibodies are also raised against autoantigens, corresponding to non-specific polyclonal activation of B-cells producing natural autoantibodies and also to antigen-driven antibodies induced by molecular mimicry Figure 2.
DNA from T. Antibodies specific to trypanosomes are induced by several parasite antigens, including variant and invariant VSG epitopes, as well as membrane, cytoplasmic and nuclear antigens, through T-dependent and T-independent pathways Reinitzand Mansfield Antibodies directed against trypanosome VSG components appeared in seraand their binding to the surface coat of the trypanosomes was able to induce a decrease in parasitemia, both in the blood and extravascular spaces, specifically by immune lysis of parasites and their destruction by the Kupffer cells in the liver.
In contrast, VSG-specific IgG does not seem to be involved in the destruction of trypanosomes, as they appeared after the disappearance of this VAT population. Another induction of antibodies, linked to the new VSG epitopes, appeared in sera and also contributed to decrease the new VAT-specific population. The VAT-specific antibodies therefore decreased to low levels, whereas antibodies, belonging predominantly to the IgM class specific to invariant epitopes, remained at high levels.
As a third option, other sources of geographic information can be used, including paper and digital maps, as well as hand-drawn, out-of-scale sketches of the endemic areas that may be available in the epidemiological reports. When all the available data sources have been exhausted, a limited but non-negligible number of settlements, especially the smaller or temporary, often remain unmapped, thus calling for further investigation. Direct consultation with first-line field workers of the NSSCPs either via face-to-face interviews, cell-phone or e-mail has proved the most speedy and cost-effective manner to locate - most frequently in relation to other known locations - hundreds of these small and often remote settlements.
The various sources of geographic information used to build the HAT Atlas are characterized by different levels of accuracy. To estimate the overall spatial accuracy of the resulting maps we classified mapped locations into four broad categories of accuracy: very high, high, moderate and low. The first category, i. These measurements can be affected by an error as little as a few metres, but we conservatively estimated an average error of 50 m.
Certain coordinates obtained from gazetteers are also included in the first category of accuracy, but only if no rounding of the coordinates was carried out i. The second category "high accuracy" includes all those cases where coordinates obtained from gazetteers have, for some reason, been rounded or truncated at the source.
For example, in the GEOnet Names Server database, which provides the baseline for many, if not all, of the available gazetteers [ 30 ], more than half of the coordinates for Africa are rounded to the nearest minute, which results in errors of up to m. For this second category we therefore estimated an average error of m.
The difference between the two categories lies in the detail of the qualitative information they are based upon. We estimate an average accuracy of 2, m and 5, m for the categories "medium" and "low" respectively. The Atlas aims to map all new HAT cases reported by affected countries. However, under certain circumstances, NSSCPs consider a seropositive individual as affected, even in the absence of parasitological confirmation.
This occurs more frequently in T. However, in the database note is taken of all the instances when NSSCPs have included seropositives without parasitological confirmation in the totality of HAT cases.
PATH celebrates progress in fight against sleeping sickness in the Democratic Republic of the Congo
As we write, mapping in 23 countries out of the 25 that reported on HAT occurrence in the period has been completed Figure 1. Data processing is considered complete when all available data sources for the study period have been analysed and entered in the database. Approximately 1 unpublished files, including epidemiological reports, maps, databases and spreadsheets, have been analyzed for the 23 study countries, thus incorporating i the results of active screening of over 2.
A total of over 42 cases of HAT and 6 different localities have been included in the database. Work is in progress to process data from the 2 remaining countries having reported the largest burden of HAT cases in the study period: Angola and DRC represented with a striped pattern in Figure 1. Efforts should be made to clarify the epidemiological status of HAT in these eight countries.
In Botswana, Namibia and Swaziland represented with a green chequerboard pattern in Figure 1 , it is suggested that transmission of sleeping sickness may have been interrupted because of successful tsetse elimination campaigns recently implemented in Botswana and Namibia [ 31 — 33 ], as well as evidence indicating that Glossina austeni - a species not involved in HAT transmission [ 34 , 35 ] - is currently the only species of tsetse fly present in Swaziland [ 36 ]. The Atlas of human African trypanosomiasis: progress status. For each country, data processing is considered complete when all available data sources for the study period have been analysed and included in the HAT database.
To date, not all cases reported from completed countries could be mapped. Table 3 shows that approximately 10 percent of cases could not be geo-referenced at the village level yet, although the focus of origin is known. The majority of gaps in mapped cases originate from passive surveillance, as the number of sleeping sickness cases may be reported as focus-level aggregates, without specific reference to the patients' village of residence. Despite actions to visit the source for more detailed data, it occurs that the necessary village-level information may have been permanently lost, especially because of the violent conflicts that ravaged numerous HAT endemic areas in recent years.
Cases of human African trypanosomiasis reported from Western Africa period Countries masked in white are i non-endemic for HAT, or ii those that did not report on the HAT epidemiological situation in the period Areas masked in grey correspond to disputed territories and non-self-governing territories [ 39 ]. Cases of human African trypanosomiasis reported from Central Africa period Countries masked in white are i those where mapping is in progress, ii those that did not report on the HAT epidemiological situation in the period Cases of human African trypanosomiasis reported from Eastern and South-eastern Africa period Countries masked in white are i those were mapping is in progress, ii non-endemic for HAT, and iii those that did not report on the HAT epidemiological situation in the period The presence of the same mangrove biotope across this porous border suggests that the disease might also be present in the territory of Sierra Leone, even though no case is reported from this country.
However, an exploratory mission carried out in early in 24 villages of Sierra Leone close to the Guinean border results included in Figure 2 failed to find evidence of HAT [ 37 ]. Nigeria reports cases from Edo and Delta States, where security constraints prevent more accurate surveys that could delineate the exact extent of the focus.
By contrast, extensive active screening surveys in Benin, Burkina Faso, Ghana, Mali and Togo have not revealed any evidence of transmission in vast areas of the Sudanian savannah ecoregion, which includes a number of sleeping sickness foci that had been active in the first part of the 20 th century [ 29 ]. This evolution appears to have been driven by demographic, climatic and landscape dynamics that would have shrunk the distribution of the tsetse fly in the region and reduced the possibility of contact between people and the vector of HAT [ 38 ].
The most active HAT foci of the Central African countries presented in this paper - which does not include Angola and DRC - are found in Sudan, Central African Republic, Congo and Uganda Figure 3 , most notably in riverine, forested biotopes where at-risk activities include attending to domestic chores, farming, fishing and hunting. A notable feature of HAT distribution in this region is the relevance of trans-boundary foci, associated to important population movements. These movements are often caused by insecurity, but also by the fact that borders frequently cut across areas inhabited by the same ethnic group.
In North-western Uganda most cases of Gambiense sleeping sickness are reported, listing from East to West, from the districts of Amuru , Adjumani, Moyo, Yumbe, Arua, Maracha-Terego and Koboko , the latter providing most of the cases reported in recent years. Other less active foci in the forest biotope can be found in Cameroon i. The second important biotope of HAT transmission in Central Africa is the mangrove swamp along the Atlantic coast, where people are at risk of infection when engaged in fishing or hunting activities.
In Cameroon we find the focus of Campo, also shared with Equatorial Guinea, which is followed southwards by the foci of Mbini and Kogo. In Eastern and South-eastern Africa, affected by Rhodesiense HAT, at-risk activities are those that bring people into areas where livestock or wildlife interact with the tsetse vector. Among these activities are grazing livestock, collection of firewood and honey, hunting, fishing and poaching.
Evidently, in addition to park rangers, tourists are among the categories at-risk, and a number of infections are diagnosed outside transmission areas in tourists that had visited protected areas. Infected tourists are considered as "exported cases" and mapped with purple triangles in points that are representative of the areas where they contracted the infection most often the centroids of the visited parks. Most reported cases of Rhodesiense sleeping sickness are linked to the livestock reservoir. Domestic cattle can be highly mobile, and their movements along trade routes and through livestock markets pose a serious challenge to Rhodesiense HAT control.
In some countries these movements have been directly linked to the emergence of new foci of HAT transmission [ 40 ]. In particular, it has been shown that animals for sale at markets tend to have a higher prevalence of infection than animals in the general population; control of this spread therefore depends on close collaboration with veterinary services [ 41 ].
The livestock reservoir is especially important for South-eastern Uganda, which accounts for over 50 percent of T. Cases are mainly reported from the districts of Iganga , Soroti and Kaberamaido. The latter, together with the Dokolo and Lira Districts, only started to report a sizable number of cases in after the northwards movements of cattle and the movements of populations due to civil unrest. This northwards shift represents a real risk of merger with the Gambiense form that affects the North West of the country, which would pose significant problems for disease control [ 42 ].
Sporadic cases of T. Domestic animals also play an important epidemiological role in other countries, including Tanzania, which reports over 30 percent of the total number of T. In the latter country, HAT cases are reported from the Western Province districts of Bungoma , Teso and Busia , with a few Kenyan cases being detected by health facilities across the Ugandan border. Sporadic cases are also reported from the Nyanza Province Migori district.
Wildlife, especially game animals, is the other central actor in the epidemiology of Rhodesiense sleeping sickness. Figure 4 shows the close spatial relationship between HAT infections and protected areas in those countries where the livestock cattle reservoir does not dominate. In a larger-scale example Figure 5 the distribution of sleeping sickness cases around the Nkhotakota Wildlife Reserve in Malawi is shown. We note that a few circles identifying HAT cases are also found within the park's boundary, as they refer to park's workers e.
Cases of human African trypanosomiasis T. Autochthonous cases are mapped in their places of residence. One exported case is mapped in the centroid of the polygon representing the park's boundaries. Zambia has been reporting cases linked to National Parks in the eastern and northern part of the country i. Mozambique is reporting sporadic cases in Tete and Niassa Provinces.
Tanzania reports cases of infection from the Serengeti and Tarangire National Parks and Ngorongoro Conservation Area in the northern part of the country.
Shop now and earn 2 points per $1
Interestingly, only the waters of Lake Tanganyika seem to separate the cases of T. The production of large scale, focus-level maps such as the one in Figure 5 is made possible by the accuracy of the geo-referencing procedures adopted for the Atlas. Results of the spatial accuracy assessment are summarized in Table 4 , which provides the number of villages by country and by category of accuracy.
If the 23 study countries are considered as a whole, the proportion of villages belonging to the 4 categories of accuracy is The resulting average accuracy, based on the estimated average error of the 4 categories, is approximately m. It must be noted that the global accuracy of the Atlas is also potentially affected by homonymies, which can cause a case of HAT to be associated to the wrong village for the only reason of this having the same name as the correct one.
It is impossible to estimate how often this may have occurred; however, thorough verifications are carried out to limit this kind of error to a minimum. Maps of disease distribution are the first, more visible output of the HAT Atlas initiative. However, when the HAT geo-database is coupled with GIS software, it enables a range of epidemiological analyses to be performed, which are of great value for planning, monitoring and evaluating HAT control programmes.
A few examples of the possible outputs of the Atlas for epidemiological analysis are given below. Figure 6A allows to monitor whether mobile teams correctly plan active case finding surveys. HAT focus of Bodo in Chad period A: Villages where HAT cases were detected through passive surveillance lilac circles and villages where active case-finding activities were carried out black dots.
B: Disease stage ratio S 1 : first stage, S 2 : second stage. The map shows that a sizable number of cases are reported by passive surveillance from an area north of Bodo Chad where no active screening was undertaken in the last five years. This indicates that, when planning for the next surveys, mobile teams should broaden the geographical scope of their activities to include this area of transmission. Figure 6B allows to evaluate the NSSCP capacity for early case detection, which has vast implications for treatment outcome, people's welfare and long-term disease control.
It must be noted that there are gaps in the field 'disease stage' of the HAT DB, as stage is not always recorded and included in the reports. This explains why for a few of the lilac circles in A there are no corresponding circles in B. In this respect, more recent data i. Another example of the Atlas as a tool for monitoring and evaluation of control activities is in Figure 7 , which shows a time series of maps for the focus of Mbini Equatorial Guinea.
Villages reporting HAT cases red circles and villages where active case-finding surveys were carried out black dots. Despite active case-finding surveys and subsequent treatment of detected cases, the focus of Mbini presents a fairly stable epidemiological pattern and the number of new infections does not show signs of abatement. The strategy for HAT control in the area should therefore be reinvigorated. Thanks to the HAT DB, another factor could be added to this analysis by estimating the ratio of 'number of people screened' to 'census', which would clarify whether poor performance in reducing the number of new HAT cases can be ascribed to insufficient coverage of active screenings, and therefore if sensitization activities should be contemplated.