Trypanosomiasis (African) - Scores for Non Tse-Tse transmitted - available
Control ToolsDiagnostics availability
GAPS:
HAT: diagnosis in humans AAT (including human infective tryps): Routine methods are described in the OIE Manual of Diagnostic Tests and Vaccines. Identification of the agent: Several parasite detection techniques can be used, including the microscopic examination of the wet and stained thick or thin blood films. The PCR, is highly specific and more sensitive and can identify parasites at the genus, species or subspecies level, depending on the cases. Serological tests: Two trypanosomal antibody detection tests, the indirect fluorescent antibody test and the antibody-detection enzyme-linked immunosorbent assay (ELISA), are routinely used for the detection of antibodies in cattle. They have high sensitivity and specificity but can only be used for the presumptive diagnosis of trypanosomiasis. NTTAT: see the OIE diagnosis standards for Surra; ELISA, OPCR CATT and parasitological tests GAP: NTTAT: For T. equiperdum: no standards, no commercial test For T. evansi: no reference test identified by OIE since no code. Will be changed. AAT (including human infective tryps): None NTTAT: Potential for T. equipderdum: small (equine sector only). Larger potential for T. evansi. No. GAP: Standardized test are highly expected as well as penside tests. Vaccines availabilityNo. No. No. No. Not applicable as no vaccines available. No. Use of genetically modified vaccines might be problematic in some countries. The field trials may need specific regulation regarding the release of GMOs into the environment. No. Could be used in Africa if there was a suitable vaccine. GAP: NTTAT: modified vaccines. Pharmaceutical availabilityResistance is developing to the anti-trypanocidal drugs. Only three compounds available for use. GAPS:
AAT & HAT: Development of drugs which can be used prophylactically. Exploit public-private partnerships such as FAP/IFAH on quality control of veterinary drugs including trypanocides. GAPS: AAT:New veterinary drugs are needed. Chemosensitization of drug resistant trypanosomes should be explored. New ways for drug delivery (antibody drug conjugates,…) should be investigated. Need to develop and establish internationally agreed Quality Control/Quality Assurance protocols for drug quality testing. No. GAP: NTTAT: no regulation adapted to French overseas department infected with T vivax and T. evansi. NTTAT: cymelarsan not registered. AAT (including human infective tryps): Not economic to produce drugs for sale in Europe and only a limited market in Africa although the existing drugs are relatively cheap, from an European point of view. NTTAT: limited market due to the cost of production under GMP standards. AAT (including human infective tryps): Not economic to produce drugs for sale in Europe and only a limited market in Africa although the existing drugs are relatively cheap, from an European point of view. NTTAT: There is a great need for new trypanocidal drugs , because trypanosomes have developed resistance against the few existing drugs. GAP: AAT: Lack of new drug development will lead to inefficiency of available drugs (problem already encountered in several areas in Africa and Asia). There is a need to create a consortium (e.g. public-private sector with the participation of research institutions) for exploring new avenues (old and new chemicals, combination of chemical preparations, etc.). New developments for diagnostic testsAAT: The development of new diagnostic tests relies on the availability of well characterized strains for the parameter to be diagnosed (drug resistance, pathogenicity/virulence,…) GAP: AAT: a public repository of characterized strains could be encouraged. In general the development of diagnostic tests is much faster and usually less expensive than developing vaccines. From development through validation to commercial availability requires time (it can take years). GAPS:
The development and validation of new tests is time consuming and labour intensive which is costly. Costs cannot be specified as they will depend on the nature of the test and the cost of producing reagents and supplying reading or processing machines if necessary Once validated there will need to be a commercial company willing to market the test. GAPS:
Does not exist at present but could be based on serological diagnosis. GAP: Pathogen freedom technology required. New developments for vaccinesAt least 200 milion Euros , but commercialisation will be very difficult due to the cost of vaccines. Depending on when a candidate vaccine could be identified there will be along timescale due to the antigenic properties of the trypanosomes. 10 years is a reasonable estimate. This will involve identification of candidate antigens, development, clinical trials and licensing. Potential vaccines need to be identified and subjected to initial trials and depending on the outcome will depend the time to commercial availability. GAP: Living modified vaccines should be evaluated for T. vivax and T. evansi. Expensive with the need to develop and undertake all the relevant tests to provide data to enable the product to be authorised. Field trial will be difficult as will evaluating the results. At least 100 million Euro. New developments for pharmaceuticalsTo be able to develop a new trypanocidal drug with a large spectrum of activity at European level (European registration requirements) the total cost will be more or less 300 million Euro NTTAT: relatively good drugs available for surra. Yet not registered everywhere, not validated in all species GAPS: AAT:In vitro culture systems are an absolute prerequisite for drug screening (T. congolense, T. vivax). AAT: Lack of new drug development will lead to inefficiency of available drugs (problem already encountered in several areas in Africa and Asia). There is a need to create a consortium (e.g. public-private sector with the participation of research institutions) for exploring new avenues (old and new chemicals, combination of chemical preparations, etc.). Time to develop would depend on the product and the trials necessary to validate the efficacy and safety. Commercial production would then take further time. Five to 10 years seems a realistic timeframe Really necessary but very little attention is payed to development of new trypanocidal. GAPS: NTTAT: Yes but very limited research work. AAT:The quality of the existing compound should be checked by independent laboratories. AAT:New veterinary drugs are needed. Chemosensitization of drug resistant trypanosomes should be explored. New ways for drug delivery (antibody drug conjugates,…) should be investigated. Need to develop and establish internationally agreed Quality Control/Quality Assurance protocols for drug quality testing. Expensive but difficult to assess as it will depend on the product and the trials necessary to validate and license. GAPS: AAT: Lack of interest of the private sector due to reduced market profits AAT: Being often a chronic, endemic disease and a disease of the poor, trypanosomiasis does not attract donor, media and private sector attention. In fact, it can be classified as “neglected disease” although it is a major pathological constraint for livestock-agriculture development and, more generally, sustainable agricultural and riral development (SARD). It is no coincidence that out of the 37 tsetse-infested countries, 32 are Low-Income food Deficit Countries and 29 are Least Developed Counries. Livestock provides important contributions to livelihhods and markets in more than 20 countries where the disease occurs. 50 to 100 million Euro. Disease detailsDescription and characteristics.AAT & HAT: Trypanosomes are flagellate protozoans that inhabit the blood plasma, the lymph and various tissues of their hosts. The genus Trypanosoma belongs to the protozoan branch, order Kinetoplastida, family Trypanosomatidae. Tsetse-transmitted trypanosomes belong to the salivarian section, subgenus Nannomonas for T. congolense, T.simiae and T. godfreyi, Duttonella for T. vivax, and Trypanozoon for T. brucei ssp.
NTTAT: Some strains of T. vivax are able to spread by mechanical transmission., T. equiperdum and T. evansi are phylogenticall closely related to the T. brucei ssp clade.
T. equiperdum is a specific and unique trypanosome of equines is not found in the bloodstream but shows remarkable tropism for the mucosa of the genital organ, the subcutaneous tissues and the central nervous system.
GAPS:
AAT & HAT: The disease affects both people [Human African Trypanosomiasis (HAT) or sleeping sickness] and animals African Animal Trypanosomiasis (AAT) or Nagana Human African Trypanosomiasis (HAT) or sleeping sickness, only occurs in Sub-Saharan Africa. It is caused by two subspecies of Trypanosoma brucei. These are T. brucei gambiense and T. brucei rhodesiense African Animal Trypanosomiasis (AAT) is caused by a number of trypanosome species and subspecies. The most important species in this disease are Trypanosoma congolense, T. vivax and T. brucei subsp. brucei. T. congolense can be classified into three types, which are called the savannah, forest and kilifi types. Other species such as T. simiae and T. godfreyi can also cause AAT. The host preferences of each trypanosome species may differ, but T. congolense, T. vivax and T. brucei brucei have a wide host range among domesticated animals. T. godfreyi and T. simiae occur in pigs. Most species are transmitted by insects. NTTAT: is caused mainly by T. equiperdum in equids by sexual transmission, by T. evansi in Camelids and by T. vivax in livestock. T. evansi and T. vivax are transmited by haematophagous insects. T.vivax is limited to cattle, water buffalo, deer, horse (Africa and Latin America), but T. evansi in present in cattle, buffalo, horse, dogs, elephant, deer, rhinoceros, capybaras, and a large range of domestic and wild animals including rodents in Africa, Asia and Latin America T.vivax can be transmitted by haematophagous insects other than tsetse flies. This species of trypanosome can cause serious disease outbreaks, particularly in Latin America, with high mortality in affected animals. T.vivax also occurs in Asia. Other trypanosome species of economic importance, and non-tsetse transmitted, are T. evansi responsible for a disease caused Surra and affecting mainly bovids, including buffaloes, and camelides. T.equiperdum is worldwide distributed, sexually transmitted and causes a severe pathology, called dourine (an OIE notifiable disease), in equines. In affected animals mortality can reach 75%. Recently, mechanical transmission of T.congolense (i.e. without the intervention of tsetse fly) has been demonstrated. T.evansi and T.vivax are pathogenic for a very wide range of mammalians and they can both cause from peracute to chronic diseases. GAPS: AAT:Factors influencing the pathogenicity/virulence of trypanosome strains such as drug resistance, host, ecological environment. Genetic markers for virulence Origin of haemorrhagic strains of T. vivax.? NTTAT: Need for identification of the vector range of NTTAT. Possible alternative routes of transmission of T. evansi (sexual?) and T. equiperdum (mechanical?) / For T. vivax: mechanisms of transmission by biting insects has to be investigated locally; . Is this a recent event ? Can tsetse transmitted change to NTTAT? AAT & HAT: Trypanosomes cannot survive for long periods outside the host, and disappear quickly from the carcass after death. Trypanosomes can surive in blood samples for about 8h (when kept cool). NTTAT: not stable, but questionable for T. evansi in stomoxys, which once infected are able to transmit for 24-48h. GAP: NTTAT: Delayed transmission of T. evansi by stomoxes ? Species involvedAAT & NTTAT: Trypanosomes can infect all domesticated and wild animals; clinical cases have been described in cattle, water buffalo, sheep, goats, camels, horses, donkeys, alpacas, llamas, pigs, dogs, cats and other domestic and wild animal species These diseases bear different common names such as nagana, dourine and surra. In cattle, trypanosomiasis is caused by T. congolense or T. vivax and to a lesser extent T.brucei. It can have an acute or chronic character. In horses extensive subcutaneous oedema is often seen in infections caused by various species of trypanosomes (T. brucei, T. congolense, T. evansi and T. equiperdum. T. evansi has a high rate of chronic or apparently healthy carriers In the domestic pig, T. simiae produces a hyperacute, fulminating disease. HAT: animal reservoir/human reservoir; there are several animal species which are a reservoir for HAT (pigs , cattle , sheep , goats, dogs and also wild ruminants and pigs, but in the mentioned species HAT is not causing disease. Primates and other monkeys can also be carriers of HAT and in these species HAT can result in disease. GAPS:
HAT: Trypanosoma brucei gambiense (T.b.g.) is found in west and central Africa. Trypanosoma brucei rhodesiense (T.b.r.) is found in eastern and southern Africa (3), although overlapping areas, where the two forms co-exist, occur. AAT: human infective T. congolense? AAT is normally not infective for humans , only two recent cases of human cases (India) of T.evansi infections are described in literature. GAPS:
HAT & AAT: Tsetse flies are only found in Sub-Saharan Africa and include all the species in of the genus Glossina . Specimen of Glossina have been caught in Saudi Arabia, near Yemen. Their role in the transmission of trypanosomes in the Arabian Peninsula is unknown. In sub-Saharan Africa, different species of tsetse fly have different habitats. They are mainly found in vegetation near rivers and lakes, in forest-galleries and in vast stretches of wooded savannah. Some 29 to 32 species and sub-species (depending on classification) have been identified. All tsetse species are potential vectors of AAT and/or HAT but only 6 of them are recognized as main vectors of sleeping sickness and incriminated in the transmission of the two pathogenic human parasites(3) Alterations of the environment and climatic changes are affecting the tsetse distribution. T. vivax can be transmitted by tsetse flies (cyclic) or by biting flies (non cyclic). NTTAT: T. vivax and T. evansi only by biting flies (Tabanidae, Stomoxyinae and hippoboscidae). T. equiperdum only by venereal transmission from stallion to mare. Particular case of T. evansi in Latin America with a biological vector (vampire vat). GAPS: AAT & HAT: Role of non-tsetse vectors, especially outside sub-Saharan Africa. Role and importance of different tsetse species in various agro-ecological zones. NTTAT:Vector identification. Exact role of Stomoxyinae in the transmission of T. evansi ? immediate and delayed transmission? Existence of other mechanical or biological vectors not yet identified ? AAT & NTTAT: Wild and domestic animals can host these pathogenic trypanosomes and under particular conditions may represent an important reservoir (especially wildlife) of infection for the vectors. HAT: A large range of wild and domestic animals can act as reservoirs of the human-infective parasites especially T.b. rhodesiense; thus domestic and wild animals are an important parasite reservoir. Animals can also be infected with T.b. gambiense, however the precise epidemiological role of this reservoir is not yet well known. GAPS: HAT: Role of animal reservoir in T. b. gambiense NTTAT: role of wild host as reservoir for livestock infection ? Reservoirs of T. evansi, role of small ruminants. No pathology yet possible reservoir? Description of infection & disease in natural hostsAAT & HAT: Transmission of trypanosomes involves three interacting organisms: the host (human or animal [livestock or wildlife]), the insect vector and the pathogenic parasite. Trypanosomiasis is transmitted to man and animals by a blood sucking insect, the tsetse fly. Direct infection, through contaminated blood and other body fluids is possible. Per oral and transplacental transmission for T brucei; iatrogenic for all. NTTAT: mechanical transmission depends on the fly picking up trypanosomes, interrupting the meal and then recommencing feeding on a different host. GAPS:
HAT & AAT: When a tsetse feeds on the blood of a parasitized host it also ingests blood-stream forms of the trypanosome. These bloodstream forms multiply within the fly and then migrate to the mouthparts (T. congolense) or the salivary glands (T. brucei). Development of T. vivax takes place in the mouthparts only. This process takes 5-13 days for Trypanosoma vivax, 15-23 days for T. congolense and 12-23 days for T. brucei. After this period, trypanosomes will be injected into a host as the fly feeds. Once infective the fly remains infective for the remainder of its life. NTTAT: mechanical transmission. GAPS: NTTAT: Biological basis of the shift between NTTAT and tsetse-transmitted T. vivax (speed of induction, reversibility, synchrony of both ways of transmission. Variability of T. vivax species unknown. AAT: Tsetse-transmitted trypanosomiasis (T. congolense, T. vivax and T. b. brucei) is a classically acute or chronic disease that causes intermittent fever and is accompanied by anaemia, oedema, lacrimation, enlarged lymph nodes, abortion, decreased fertility, delayed sexual maturity, loss of appetite and weight, leading to early death in acute forms or to digestive and/or nervous signs with emaciation and eventually death in chronic forms. The severity of symptoms is related to the gradient of susceptibility to trypanosome infections and pathogenicity of species and strain of the infective trypanosome. The morbidity and mortality rates are high, Generally, wild mammals and some humpless Bos taurus African cattle (the N Dama and the various West African Shorthorn breeds) and small ruminant (Djallonk sheep, Dwarf West African goats) breeds posses a certain degree of tolerance to the infection and appear to be able to control the anaemia it causes. This trypanotolerance also extends to crossbred cattle breeds (Bos indicus x Bos taurus) such as the Méré.
HAT: T. b. gambiense (chronic form of HSS) and T. b. rhodesiense (acute form of HSS). Usually not very pathogenic in livestock.
NTTAT: T. evansi see AAT: above, mainly in cattle , horses , camels and eventually in dogs, without treatment the disease is fatal . T. equiperdum: fever, swellings and local oedema of the genital organs and mammary glands, oedematous eruptions of the skin, anaemia, emaciation , ocular lesions , lack of coordination in the limbs , facial paralysis and continuing appetite. Pregnant mares may abort or foal normally.
GAPS:
AAT: (including human infective tryps species): In cattle, small ruminants and equines the disease becomes apparent about seven to ten days after the bite of a trypanosome infected fly with a range of the incubation period for African animal trypanosomiasis from 4 days to approximately 8 weeks. Infections with more virulent isolates have a shorter incubation period when the disease can become apparent in 7 to 10 days in cattle and small ruminants after an infective tsetse bite. NTTAT: T. equiperdum: from 3 to 3 or more months. T. evansi: very difficult to know, from days to years depending of the age of the animal , health status, stress etc… GAP: NTTAT: needs to be studied in NTTAT. AAT (including human infective tryps species): Mortality varies with the breed of the animal, as well as the strain of the infecting organisms. In untreated cattle and equines infected with some strains, the mortality rate can reach 50-100% within months after exposure, particularly when poor nutrition or other factors contribute to debilitation. More generally, field studies in many endemic areas indicate that AAT increases death rates in exposed cattle populations by about 2 percentage points. . NTTAT: T. evansi is responsible of very high rates of death in newly infected area in horses. Without treatment, T. evansi infections or almost fatal.. Mortality rates due to T. equiperdum depend of the clinical form (mild to very severe depending of the pathogenicity of the trypanosome and general condition of the host) The infection persist for one or two years generally and about half of the animals die during that time. Some animals may remain infected for 3 to even 5 years. GAPS:
AAT & HAT: Blood-borne and not shed. Depends on mechanical transmission by biting flies or cyclical transmission by tsetse. NTTAT: sexuel transmission T. equiperdum. The mechanisms of pathogenesis are poorly understood. Immunosuppressive effects of T. evansi are responsible for disease outbreak and vaccination failure. GAPS:
Zoonotic potentialHAT: WHO estimated that in 2000 some 50 to 60 million people in Africa were exposed to contract sleeping sickness through the bite of the tsetse fly. At that time WHO considered that close to 300 000 children, women, and men on the African continent were affected by the disease, a figure which was much larger than the 27 000 cases diagnosed and treated that year. Since that date wide-ranging control programmes have been undertaken and the population under surveillance was substantially increased. In 2007, the number of new cases reported had already fallen to 10 769. (3) Ongoing mapping of HAT foci (9) has helped to obtain a more precise idea of the population at risk and screening operations are helping in obtaining a good estimate of incidence. NTTAT: rare atypical cases (T. evansi, T vivax, T. lewisi). GAPS:
HAT: Difficult to assess the current situation in a number of endemic countries because of a lack of surveillance and diagnostic expertise. Because the symptoms are shared with a number of other more common illnesses, under-reporting is common. Scientific studies have been undertaken which indicated that for T. b. rhodesiense approximately 60% of cases are reported in areas with a good health infrastructure and awareness of the disease. For T. b. gambiense, diagnostic limitations and levels of uptake of screening programmes can also result in about 40% of cases not being diagnosed in an initial survey. Elsewhere, in the absence of active surveillance and/or awareness of the disease, under-reporting rates may be higher. NTTAT: unknown. GAPS:
HAT: The disease affects mostly poor populations living in remote rural areas of Africa. Travelers visiting the sub-Saharan part of the continent may also become infected when they travel through tsetse infested zones. There is basically no risk of sleeping sickness transmission in urban areas; however, peri-urban transmission has been recently described in Kinshasa and Luanda. GAP: NTTAT: evaluation of contact human-parasite in exposed human population (veterinaries, farmers, slaughter house technicians, rural population / ingestion of row meat and blood etc). HAT: Human African Trypanosomiasis takes two forms, depending on the parasite involved:
NTTAT: fever, oedema, anaemia (T. evansi or T lewisi). GAP: NTTAT: need to identify human cases in rural population. HAT: Mother-to-child infection: the trypanosome can cross the placenta and infect the foetus. Otherwise, spread from human to human is only via the vector, but several family members, especially mothers and young children, can be thus affected. Impact on animal welfare and biodiversityAAT & HAT: Animal disease poses a welfare problem. This is most often a chronic disease, and trypanocides are both costly and sometimes unobtainable so that animals may be ill and suffering for considerable periods. AAT (including human infective tryps species): Most wild animals are known to be susceptible to infection. However, as the natural hosts of tsetse, wild animals are trypanotolerant if not stressed. The disease is not thought to be implicated in threatening the survival of any endangered species. NTTAT: T. evansi grows in all mammals with gross pathology in deer, ocelot, howler monkeys , tapir , tiger, orang-utan, lion, elephant. GAP: NTTAT: prevalence in wild hosts AAT (including human infective tryps species): No NTTAT: T. equiperdum normally in all cases; T. evansi in case of highly chemo-resistant strains. GAP: NTTAT: is it necessary or not to slaughter the animals to eliminate the parasite ? Geographical distribution and spreadAAT & HAT: Occurs in 37 sub-Saharan countries covering about 9 million km2, an area which corresponds approximately to one-third of the Africa s total land area and includes Africa’s rain forests. The infection threatens an estimated 50 million head of cattle. Trypanosomes, particularly T. vivax, may spread beyond the “tsetse fly belt” by transmission through mechanical vectors. NTTAT: T. vivax, T. evansi and T. equiperdum is also found in South and Central America and the Caribbean, areas free of the tsetse fly. T. evansi is also found in the Indian sub-continent, Asia, southern Europe (Canary Islands, some cases in camels and horses in Spain very recently. T. equiperdum in Eastern Europe , some old Russian republics and Africa,. Due to enormous horses transport all over the world, it is a real threat for the horse population of any country in the world. Its distribution inside these infested areas may change. GAPS: NTTAT:
AAT: In Africa, where the parasites are transmitted by tsetse flies, trypanosomiasis appears as a persistent endemic disease. HAT: The disease in humans is associated with periodic massive outbreaks, with low prevalences of 0.1%, increasing to over 1% and, if unchecked, leading to the infection of virtually all members of affected communities. Historically, these epidemics have been devastating leading to the depopulation of some affected areas. NTTAT: In South America, where T. vivax is transmitted strictly by mechanical vectors, trypanosomiasis occurs in cattle as epizootics separated by a few years when the disease appears to be silent and subclinical. After a series of outbreaks, animals tend to be immune and maintain the parasites in very low numbers. Once the susceptible population increases the disease returns T. evansi transmitted by biting flies is a persistent endemic disease. GAPS: AAT: What is the role of trypanocidal drug resistance on the endemicity of trypanosomiasis in livestock? Does trypanocidal drug resistance contributes to the creation of an endemic situation? NTTAT: economical impact of such periodic outbreaks? Currently endemic in northern Africa, very recent two outbreaks in mainland Europe due to importation of camels from Gran Canaria. Urgent follow-up needed. Risk assessment needed for importation of T. evansi into EU Risk assessment of importation of T equiperdum from Asia into EU (through import from Russia via eg Poland) needed. AAT & HAT: Most tsetse populations show regular fluctuations which are correlated with seasonal changes in temperature and relative humidity. During the hot season in Zimbabwe for instance, when temperatures regularly approach 40°C, tsetse numbers decline by around 90%. This is thought to be due to temperature-related increases in reproductive abnormalities and adult mortality.
NTTAT: less seasonal than tsetse-transmitted trypanosomes. Only in regions and seasons with very high temperatures and very dry climate the number of biting flies may decrease and so the risk of infection may reduce but not disappear.
GAPS:
AAT: Potentially could spread rapidly within an area but dependant on the vector range, number of tsetse and the infection rate and movement of hosts. HAT: focal nature + potential for spread (cfr Uganda). The disease is associated with recognised geographical foci which have changed very little over time, however there have been some extensions of these foci, notably in the T. b. rhodesiense areas where cattle imported from HAT endemic areas have brought in the disease, leading to rapid spread over 2-3 years. NTTAT: linked with healthy carriers movements. Could potentially spread rapidly within an area but dependant on the vector range, number of biting flies and the infection rate. GAPS:
AAT: Most trypanosomes are transmitted by tsetse flies, and can only become established in areas where these vectors exist; however, T. vivax does not require tsetse flies and can become endemic in other areas as it has in parts of South America. Tsetse fly does not recognise boarders and the problem is of transboundary nature, often involving several countries in a region. NTTAT: highly important especially in the case of T. evansi in Asia with important animal movements from India and China to South East Asia, and interference with Foot and Mouth Disease vaccination. NTTAT can become endemic in any country with a mild to tropical climate i.e. everywhere where biting flies can survive. GAPS:
AAT: seasonality associated with the seasonal changes in the extend of the tsetse fly belt and the density of flies and movements of hosts. NTTAT: linked to seasonal activity of biting insects. AAT & HAT: distribution of vector largely determined by climatic factors NTTAT: possible increases of biting insect density AAT & HAT: Possibly – extreme hot seasons can impact on tsetse populations and hosts. NTTAT: weather associated possible increases of biting insect density AAT & HAT: Climate change may result in a change in the vector geographical range with spread to some areas and regression in other areas in response to dryer conditions and human activity reducing land cover. NTTAT: biting insects such as stomoxys may proliferate in tempered countries. Due to the increase of temperature the biting flies may become a danger for actually cold and mild climate regions. GAPS:
Route of TransmissionAAT & HAT: African trypanosomiasis is mainly cyclically transmitted through the bite of the tsetse flies NTTAT: T. evansi and T. vivax transmitted by biting flies to herbivores, T. evansi perorale to carnivores and T. equiperdum sexual (equidae). GAPS:
AAT & HAT: Carnivores may be infected with T. brucei by ingesting meat or organs from infected animals. In this case, infection occurs probably through the mucosa of the mouth in which bone splinters make wounds through which the parasites penetrate. Mechanical transmission possible but importance not known. NTTAT: T. evansi by ingestion of meat and organs of infected animals and iatrogenic transmission. Transplacental transmission in T. evansi and T. vivax. GAPS: NTTAT: role of other vectors (biting arthropods vor other hematophagous invertebrates). AAT (including human infective tryps species): Density and distribution of cattle and tsetse flies and factors which increase contact between the vector and the host (e.g. watering points). Presence of parasite species (HAT). NTTAT: animal movements, density of biting flies, animal population density. GAPS:
Detection and Immune response to infectionAAT (including human infective tryps species): The immune response is unable to completely eliminate trypanosomes, and animals can become inapparent carriers. These inapparent infections can be reactivated if the animal is stressed. NTTAT: immune control possible for T. vivax and T. evansi after sometime and after trypanocidal treatments. Stress will cause increased pathology. GAPS:
AAT & HAT: Several antibody detection techniques have been developed to detect trypanosomal antibodies for the diagnosis of trypanosomiasis, with variable sensitivity and specificity (e.g. CATT, ELISA). NTTAT: Semi-commercial kits exist for T. evansi in casu CATT and ELISA. GAP: Need for proficiency testing and validation of serological tools in view of their “fitness for purpose”. Main means of prevention, detection and controlAAT: Protecting animals from trypanosomiasis is difficult in endemic areas, as bites from tsetse flies and a variety of other insects must be prevented. T.vivax does not require tsetse flies to become endemic in other areas. NTTAT: T. evansi: efficacy of treatment in various host species is variable. T. equiperdum: all affected or suspected and serological positive animals have to be slaughtered. Treatment is in most countries not allowed. GAP: NTTAT: evaluation of sterilizing treatments (e.g. melarsomine) to eliminate T. evansi and T. equiperdum. Establishment of effective doses in various host species (e.g. horse, buffalo, cattle, pig …) AAT & HAT: The integration and adaptation of the various control measures to the local prevailing environmental and agro-ecological conditions is essential to give optimum results 1. use of prophylactic trypanocidal (animal form of the disease) and curative (both human and animal forms) drugs, although drug resistance can be seen 2. exploitation of trypanotolerant livestock breeds 3. reduce or eliminate tsetse fly population density in a given area with traps, insecticide-impregnated targets, insecticides applied from aircraft and other means 4. protection of individual animals by using insecticide-impregnated netting or fencing, which will also reduce fly density in the locality 5. Use of insecticides on animals, usually cattle, (applied by spraying or pour-ons) to reduce the population of tsetse in an area, the insecticides used usually also kill ticks 6. If and where fly populations are isolated, an area-wide integrated intervention approach can be envisaged to create sustainable tsetse-free zone. The latter appears particularly attractive, as it permits the definite elimination of the vector from the targeted area. 7. Where the creation of tsetse-free zones is the objective, the use of the sterile insect technique is advocated where residual tsetse fly populations persist after their numbers have been reduced using other means. NTTAT: use of curative trypanocidal drugs, use of insecticidal drugs. No large-scale vector control, almost no prophylsactic use of drugs. GAPS:
AAT (including human infective tryps species): Parasitological methods: These methods aim at detecting the parasite itself mainly in blood through microscopical examination of thick or thin blood stained smear. Another parasitological method is through concentration of trypanosomes through blood centrifugation and microscopic examination of the interface (buffy coat) between the white and red blood cell, where trypanosomes are concentrated. From live animals, the parasite can be isolated from blood and lymph collected from lymph node. A blood or lymph sample of suspected infected animals can be injected in one or more laboratory animals (mouse, rat or rabbit). Serology: The detection of antibodies indicates that there has been an infection but as antibodies persist for some time (weeks or months) after all trypanosomes have disappeared from the animal (e.g. following drug treatment) a positive result is no proof of active infection. Molecular tests: Sequences of nucleotides specific for the various species of trypanosomes can be detected in fluids (mainly blood) of mammalian host. These tests can only be carried out reliably in well-equipped laboratories by specifically trained staff, and are still mainly research tools. NTTAT: see for AAT GAPS:
AAT (including human infective tryps species) and NTTAT: No vaccines are available at the present time and perspectives to have a vaccine in the short-medium term are rather scarce. GAPS:
AAT (including human infective tryps species): Trypanocidal drugs for use in cattle are limited to the salts of just three compounds:
Drugs may be used therapeutically for the treatment of an ongoing trypanosome infections or to prevent infection. Some drugs may be used for either purpose, while those which are eliminated rapidly are limited to therapeutic use. NTTAT: Melarsomine, Quinapyramine. Isometamidium based drugs (not very effective in Africa against T. evansi, but still effective in Asia ,diminazene based drugs and Melarsomine. Cymelarsan for use in camelids T. equiperdum: cymeralsan seems to be effective (Hagos et al 2010) but not allowed by OIE. GAPS:
None: (i) Some trypanocides (e.g. homidium) are considered potentially carcinogenic and acting on animal genetic material. (ii) The application of the Sterile Insect Technique (SIT) implies the use of a nuclear radio-active source for insect sterilization. Trypanomose infections compromise the immunosystem and animals may become more susceptible to disease agents of relevant biosecurity importance. GAPS: AAT: Lack or poor of information on mis-use of therapeutic measures and complexity of the SIT application. NTTAT: as per AAT for the use of trypanocides. AAT (including human infective tryps species): No specific rules laid down in the OIE Animal Health Code although trypanosomiasis due to T. congolense in bovine was included in the former List B of OIE.. It is essential that livestock are treated with trypanocides before being moved to new areas in order to prevent the spread of HAT in T. b. rhodesiense areas. Treatment of all cattle in markets should therefore be recommended. NTTAT: Regulation to be established for T. evansi T. equiperdum: OIE animal health code. GAPS:
AAT (including human infective tryps species): Prophylactic use of trypanocidal drugs to prevent the disease in animals protects people as well as animals from illness since in many rhodesiense HAT areas domestic cattle are now the main reservoir of the human infective T. b.rhodesiense. NTTAT: regular use of insecticidal drugs on the animal and its direct environment , animal movement and quarantine rules. GAPS: Need for vaccines and therapeutics. AAT (including human infective tryps species): The antibody ELISA is a very useful test for large-scale surveys to determine the distribution of tsetse-transmitted trypanosomiasis. Sample collection and storage is made easy through the use of filter papers. (1) NTTAT: idem for T. vivax and T. evansi. T. equiperdum: regular clinical control of horses and donkeys. CFT testing of all equines for export. GAPS:
AAT & HAT:
NTTAT: historical temporary infection in the French West Indies (T. vivax) and in Australia (T. evansi); recent temporary outbreak in France (currently under surveillance). Eradication of biting flies for T. evansi and T. vivax is impossible. Eradication of T. equiperdum is possible by slaughter of all affected , suspected and serological positive animals ( USA, Canada , several European countries). Dourine was eradicated in EU after WWII through treatment, castration and slaughtering. GAPS:
AAT: Infection treatment costs are high (more than US$1/treatment/animal and higher for prevention treatement). Elimination of tsetse is also expensive (for instance use of SAT can cost between US$250 and US$400 per square km). HAT: Treatment costs vary greatly according to which drug regime is used, the duration of hospital stay and whether patients are diagnosed in the first or second stage of the disease (when the central nervous system has become involved), costs are estimated to range between US$ 100 and US$ 800 per patient, most often between $100 and $250. Currently, new drug regimes and shorter hospital stays are being introduced for the second stage of the disease. AAT: To end-users the cost of trypanocide generally varies between $0.6 and $2 a dose. The cost of administering ranges from the cost of needles and syringes, where livestock keepers inject their animals themselves to over US$20. Typical fees are in the US$2 - $4 bracket. Vector control: The cost of controlling tsetse varies greatly depending on the method used and whether the objective is to maintain tsetse control over a number of years or to create tsetse free zones and protect them from reinvasion. To cite some examples, very rough orders of magnitude indicate that creating tsetse free zones using aerial spraying is likely to cost US$ 600 per sq km excluding the substantial ongoing costs of preventing reinvasion. Ongoing suppression of tsetse numbers to very low levels, using insecticide-treated cattle is likely to cost between US$ 25 and US$ 100 per sq km, depending on how much insecticide is used, how it is applied and the costs to livestock keepers in time and money. GAPS:
Disease information from the OIEYes: Surra (Trypanosoma evansi) is notifiable. Trypanosomia evansi: http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/TRYPANO_EVANSI_FINAL.pdf Tse-Tse transmitted trypanosomiasis: http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/TRYPANO_TSETSE_FINAL.pdf None. Trypanosoma evansi infections (including Surra): http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.17_TRYPANO.pdf Trypanosomosis (tse-tse transmitted): http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.04.18_TRYPANOSOMOSIS.pdf Socio-economic impactHAT: Untreated, the disease is always fatal in humans and devastating epidemics have occurred over the last century, leading to depopulation of whole settlements. The disease tends to affect the active adult population and sick individuals need a great deal of care. Many are not diagnosed as HAT patients and die as a result. The labour burden on affected households is thus considerable. The financial burden per treated patient is also considerable, variously estimated at the equivalent to 2 to 10 months of an average rural wage. The average DALYs per untreated patient have been estimated at 24 for T. b. rhodesiense and between 27 and 33 for T. b. gambiense. Total annual DALY estimates range from 1.5 – 2 million. This global figure understates the impact of the disease, as it is highly focalised so that very heavy burdens are imposed in affected communities. For example, one study showed that, comparing HAT to malaria, there were133 times as many cases of malaria reported, but these only caused 3 times as high a DALY burden. GAPS: HAT:
HAT: Treatment is expensive, normally ranging from US$150 to US$800 per person, and in the later stages of the disease treatment itself involves some 5% mortality. GAP: HAT: Critical and quantitative analyses of socio-economic costs and benefits of control are scant. AAT: All these diseases have an economic impact on the development of agriculture in Africa. Those affecting cattle are undoubtedly the most important economically since they are a major cause of reduced meat and milk production and limit the use of draught power for agricultural production. The economic losses due to reduced meat and milk from cattle production alone are estimated to be the range of US$ 1.0 - 1.2 billion. Tryps is also thought to reduce calving rates by 5 to 20 percentage points, kidding and lambing rates by 20 to 30 percentage points and milk yields by 2-25%. NTTAT: see AAT above. High in recent outbreak and mild in enzootic situation; surra : model of impact of subclinical infection developed in the Philippines. GAPS: AAT:
NTTAT: Surra : impact of subclinical infection to be evaluated in Asian countries. Need for socio-economic impact studies of NTTAT. AAT: Approximately 35 million doses of trypanocidal drugs are administered annually), with a cost estimated at more than US$40 million for purchasing drugs only. Taking this figure of 35 million doses per annum it is likely that Africa’s livestock keepers are spending some US$90 - US$140 million per annum on drugs to prevent or treat trypanosomiasis. A proportion of this cost is borne by the public purse, where the cost of administering trypanocides is paid for or subsidized by veterinary services. Tsetse control: Current expenditure on tsetse control is unknown. Farmers are spending substantial sums on pour-ons and spraying their cattle, which also helps to control ticks. Public project’s costs can be found out on a case by case basis. Funding is very sporadic, with almost all African countries closing down or merging their specialist tsetse control units, so that public investment relies on occasional projects. NTTAT: see AAT. GAPS:
AAT: Trypanosomiasis in livestock has a severe impact on agriculture in sub-Saharan Africa. Trypanosomiasis limits the use of work oxen and hence the acreages cultivated, and also, together with tick-borne diseases, constrain the upgrading of livestock, for example using grade dairy cattle. In tsetse-infested countries, half of the population suffers from food insecurity. The overall impact extends to restricted access to fertile and cultivable areas, imbalances of land use and exploitation of natural resources and compromised growth and diversification of crop-livestock production systems, including use of upgraded, more productive animal breeds (meat and milk production). GAPS:
Trade implicationsAAT (including human infective tryps species): None NTTAT: T. equiperdum is notifiable, may cause export problems. So far no rules for T. evansi but risk is there GAPS: NTTAT: a real gap exists in the regulation and prevention of introduction of T. evansi into Europe. AAT (including human infective tryps species): None. NTTAT: T. evansi: no regulation. GAP: NTTAT: Regulation to be established. AAT (including human infective tryps species): None NTTAT: T. equiperdum? Main perceived obstacles for effective prevention and controlAAT:
HAT:
NTTAT: standardisation & validation of tests for dourine/ absence of rules and regulations for T. evansi (tests exist but are not compulsory). Difficult detection of healthy carriers; absence of protocol to identify healthy farms for exportation of camelidae (surra). GAPS: AAT: Need full and effective commitment of national and local authorities and participation of local communities. Up to know, absence of integration of different control methods and synergistic exploitation of comparative advantages of various control techniques. No vaccine available. Reduced efficacy of trypanocides due to poor quality and drug resistance in trypanosome populations. Need for quality control in trypanocides. Limited financial and human resources of national veterinary services and NARS. HAT:
NTTAT: need for a highly sensitive test AND that can distinguish T. equiperdum (trading of infected animals forbidden) from T. evansi. Main perceived facilitators for effective prevention and controlAAT: The greater availability of animal health workers and private veterinarians has, to some extent, helped to make both trypanocides and their administration more accessible to livestock keepers – although probably not sufficiently to compensate for the massive reduction in government veterinary services in the last two decades. HAT: Country level, WHO, bilateral and NGO HAT control programmes have brought the recent resurgence of the disease under control. There are more trained individuals and the basic infrastructure for ongoing surveillance now exists. Tsetse control: Efforts to control tsetse continue at two levels:
NTTAT: diagnosis and treatment. GAPS:
RiskAAT (including human infective tryps): Sustained tsetse control on various scales is feasible (in large parts of sub-Saharan Africa) and low-cost effective options exist. Creation of permanent tsetse free zones is also possible, but preventing reinvasion is in important issue in all but a limited number of isolated populations. The development of drug resistant trypanosomes will lead to potential increased levels of disease in animals and humans. Whilst the use of insecticides to kill tsetse, applied from aircraft, to cattle (so as to control both tsetse and ticks) or to stationary targets and traps, is effective there is the possibility of development of insecticide resistant tsetse flies (risk is probably low but behavioural resistance could become an issue). NTTAT: indirect risk for surra is the immunosuppressive effects which can enhance intercurrent diseases and interfere with vaccination campaigns. Eradication is impossible. T. evansi: possible risk for introduction into EU. T. equipderum: idem, need for more vigilance. GAP: NTTAT: CODE, test validation, rules and regulations on EU level for Surra! ConclusionThe prospects of developing a vaccine are very poor as the trypanosomes have evolved a system to evade the host’s immune system by varying the structure of their surface coating. This change is controlled genetically and each parasite has a huge so-called ‘repertoire’ of variable antigenic type (VATs). As the host’s immune system responds to one VAT, the parasite switches to another and thereby evades destruction. Within any particular geographical area, there will be several species, subspecies, types and strains of trypanosome, each with its own repertoire of VATs. Consequently, livestock cannot develop an effective immunity to the disease. GAPS: AAT:In livestock, is there a decrease in humoral immunity linked to trypanosomiasis (potential of vaccines against secreted proteins causing anaemia). Due to its biological nature and its links with the agro-ecological settings, the disease constitutes a complex and vast sub-Saharan problem to be solved. Investments have to spread over five main areas: (i) human resource development; (ii) improved technology for diagnosis and disease treatment; (iii) improved vector control; (iv) increased exchange of information; and (v) regional, national and local institutional support. Due to this complexity, not a single agency/institution can cope with the magnitude of the challenges ahead. Therefore, a consortium of coordinated and concerted actions is needed. |
