12884 Ahmad, K., 2002. Tsetse eradication programme under fire. Lancet Infectious Disease, 3 (1): 4.
This news item describes the diverse opinions held by experts concerning the plans to release masses of sterilized tsetse flies in an attempt to eradicate the vector of trypanosomiasis in Africa.
12885 Cox, F.E.G., 2002. History of human parasitology. Clinical Microbiology Reviews, 15 (4): 595-612.
Cox: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. [[email protected]]
Humans have acquired as parasites about 300 species of helminth worms and over 70 species of protozoa. Of these parasites about 90 may be regarded as relatively common species, and some cause what are amongst the most important diseases in the world. Most of these parasitic diseases are tropical. Short but comprehensive reviews are given of many of these parasitic diseases, including an item on African Trypanosomiasis and Sleeping Sickness.
12886 Cox, F.E.G., 2004. History of sleeping sickness (African trypanosomiasis). Infectious Disease Clinics of North America, 18 (2): 231-245.
Cox: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. [[email protected]]
Infections with subspecies of the protozoan parasite Trypanosoma brucei cause important wasting diseases in Africa (nagana in cattle and sleeping sickness in humans). These diseases were little known until the end of the nineteenth century when serious epidemics of nagana were reported and raised concern among the colonial powers. The early history of sleeping sickness revolves around the discovery of the causative organism, its mode of transmission, and its life cycle in the tsetse fly. The history continues into the twentieth century with the discovery of how the parasites evade the immune response, frustrating the development of a vaccine; the failure to develop cheap and effective drugs; and the development of alternative approaches to control the tsetse fly vector.
12887 Ellis, J.T., Morrison, D.A. & Reichel, M.P., 2003. Genomics and its impact on parasitology and the potential for development of new parasite control methods. DNA and Cell Biology, 22 (6): 395-403.
Ellis: Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, Westbourne St, Gore Hill, NSW 2065, Australia. [[email protected]]
Parasitic organisms remain the scourge of the developed and underdeveloped worlds. Malaria, schistosomiasis, leishmaniasis and trypanosomiasis, for example, still result in a large number of human deaths each year worldwide, while drug resistance among nematodes still poses a major problem to the livestock industries. Genome projects involving parasitic organisms are now abundant, and technologies for the investigations of the parasite transcriptome and proteome are well established. There is no doubt that the era of the omics (comparative molecular studies of the nucleic acids and proteins) has arrived in the science of parasitology, and current trends in the discipline are addressing fundamental biological questions that can make best use of the new technologies, as well as the vast amount of new data being generated. Will this become the golden age of molecular parasitology, leading to the control of parasitic diseases that have plagued mankind for hundreds of years? The primary aim of this paper is to review advances in the general area of parasite genomics, and to outline where the application of omics technologies can and have impacted on the development of new control methods for parasitic organisms.
12888 Hendrickx, G., de la Rocque, S. & Mattioli, R.C., 2004. Long-Term Tsetse and Trypanosomiasis Management Options in West Africa. PAAT Technical and Scientific Series, No 6. FAO, Rome. pp 57. [See notice in Section A, News]
12889 Lamprey, R.H. & Reid, R.S., 2004. Expansion of human settlement in Kenyas Maasai Mara: what future for pastoralism and wildlife? Journal of Biogeography, 31 (6): 997-1032.
Lamprey: Uganda Wildlife Authority, PO Box 3530, Kampala, Uganda. [[email protected]]
Wildlife and pastoral peoples have lived side-by-side in the Mara ecosystem of southwestern Kenya for at least 2000 years. Recent changes in human population and landuse are jeopardizing this co-existence. The aim of the study is to determine the viability of pastoralism and wildlife conservation in Maasai ranches around the Maasai Mara National Reserve (MMNR). A study area of 2 250 km2 was selected in the northern part of the Serengeti-Mara ecosystem, encompassing group ranches adjoining the MMNR. Emphasis is placed on Koyake Group Ranch, a rangeland area owned by Maasai pastoralists, and one of Kenyas major wildlife tourism areas. Maasai settlement patterns, vegetation, livestock numbers and wildlife numbers were analysed over a 50-year period. Settlement distributions and vegetation changes were determined from aerial photography and aerial surveys of 1950, 1961, 1967, 1974, 1983 and 1999. Livestock and wildlife numbers were determined from re-analysis of systematic reconnaissance flights conducted by the Kenya Government from 1977 to 2000, and from ground counts in 2002. Corroborating data on livestock numbers were obtained from aerial photography of Maasai settlements in 2001. Trends in livestock were related to rainfall, and to vegetation production as indicated by the seasonal Normalized Difference Vegetation Index. With these data sets, per capita livestock holdings were determined for the period 1980-2000, a period of fluctuating rainfall and primary production. For the first half of the twentieth century, the Mara was infested with tsetse flies, and the Maasai were confined to the Lemek Valley area to the north of the MMNR. During the early 1960s, active tsetse control measures by both government and the Maasai led to the destruction of woodlands across the Mara and the retreat of tsetse flies. The Maasai were then able to expand their settlement area south towards MMNR. Meanwhile, wildebeest (Connochaetes taurinus) from the increasing Serengeti population began to spill into the Mara rangelands each dry season, leading to direct competition between livestock and wildlife. Group ranches were established in the area in 1970 to formalize land tenure for the Maasai. By the late 1980s, with rapid population growth, new settlement areas had been established at Talek and other parts adjacent to the MMNR. Over the period 1983-99, the number of Maasai bomas in Koyake has increased at 6.4 percent per annum (pa), and the human population at 4.4 percent pa. Over the same period, cattle numbers on Koyake varied from 20 000 to 45 000 (average 25 000), in relation to total rainfall received over the previous two years. The rangelands of the Mara cannot support a greater cattle population under current pastoral practices. With the rapid increase in human settlement in the Mara, and with imminent land privatization, it is probable that wildlife populations on Koyake will decline significantly in the next 3-5 years. Per capita livestock holdings on the ranch have now fallen to three livestock units/reference adult, well below minimum pastoral subsistence requirements. During the 1980s and 90s the Maasai diversified their livelihoods to generate revenues from tourism, small-scale agriculture and land-leases for mechanized cultivation. However, there is a massive imbalance in tourism incomes in favour of a small elite. In 1999 the membership of Koyake voted to subdivide the ranch into individual holdings. In 2003 the subdivision survey allocated plots of 60 ha average size to 1 020 ranch members. This land privatization may result in increased cultivation and fencing, the exclusion of wildlife, and the decline of tourism as a revenue generator. This unique pastoral/wildlife system will shortly be lost unless land holdings can be managed to maintain the free movement of livestock and wildlife.
12890 Leander, B.S., 2004. Did trypanosomatid parasites have photosynthetic ancestors? Trends in Microbiology, 12 (6): 251-258.
Leander: Canadian Institute for Advanced Research, Program in Evolutionary Biology, Departments of Botany and Zoology, University of British Columbia, Vancouver BC, V6T 1Z4, Canada. [[email protected]]
Some molecular phylogenies of plastid-like genes suggest that chloroplasts (the structures responsible for photosynthesis in plants and algae) might have been secondarily lost in trypanosomatids parasites. Chloroplasts are present in some euglenids, which are closely related to trypanosomatids, and it has been argued that chloroplasts arose early in the diversification of the lineage Euglenozoa, to which trypanosomatids and euglenids belong (plastids-early hypothesis). This article reviews how euglenid ultrastructural systems are functionally integrated and phylogenetically correlated. Here it is argued that chloroplast acquisition profoundly altered the structure of certain euglenids, and that the complete absence of these modifications in other euglenozoans is most consistent with their never having had a chloroplast. Ultrastructural evidence suggests that chloroplasts arose relatively recently within a specific subgroup of euglenids and that trypanosomatids are not secondarily non-photosynthetic (plastids-recent hypothesis).
12891 Mattioli, R.C., Feldmann, U., Hendrickx G., Wint, W., Jannin, J. & Slingenbergh, J., 2004. Tsetse and trypanosomiasis intervention policies supporting sustainable animal-agricultural development. Food, Agriculture and Environment, 2 (2), April 2004, online.
Mattioli: Food and Agriculture Organization of the United Nations, Rome, FAO, Viale delle Terme di Caracalla, 00100 Rome, Italy. [[email protected]]
In tsetse and trypanosomiasis (T&T) infested areas and countries the poverty and food security status of communities is rather heterogeneous and so is the impact of trypanosomiasis on the agricultural production process. Therefore, intervention to reduce or eliminate the impact of the disease requires, beyond an analysis of technical feasibility, a full appreciation of the causal relationship between poverty and the tsetse related development constraints. T&T intervention needs to be conceived and implemented in the context of sustainable agriculture and rural development (SARD). Hence, areas are selected not just on technical grounds but, most importantly, on the basis of their potential for sustainable and improved agricultural production. Under the umbrella of the Programme Against African Trypanosomiasis, and in collaboration with the Pan African Tsetse and Trypanosomiasis Eradication Campaign of the African Union, a set of criteria and guiding principles for prioritization of intervention areas has been established to facilitate this approach. In order to maximize benefits of interventions, a concept for Area-Wide Integrated Pest Management (AW-IPM) has been developed. AW-IPM targets the entire pest population and capitalizes on locally prevailing factors and favourable trends (agro-ecological, climatic and demographic) assisting a reduction of fly challenge and disease risk. Substantial benefits from interventions against T&T are predicted for the mixed crop-livestock systems of the cotton belt running through parts of Burkina Faso and Mali, and the Southern Rift Valley of Ethiopia. Blending the technical AW-IPM approach and the SARD policy increases the chances of technical success, yields maximal economic returns which, in turn, paves the road for a move away from subsistence and towards market agricultural practices.
12892 Omamo, S.W., Kagwanja, J., Reid, R., dIeteren, G., Ndiwa, N., Nyabenge, M., Matere, C. & Mulatu, W., 2002. Agricultural extension reform in Africa: insights and lessons from livestock disease control in South-West Ethiopia. Socio-economics and Policy Research Working Paper - International Livestock Research Institute, 2002, No. 46, pp. iii + 13.
Omamo: International Service for National Agricultural Research (ISNAR), ECAPAPA, P.O. Box 765, Entebbe, Uganda. [[email protected]]
Agricultural extension systems across Africa are under great pressure to become more efficient and effective. Whereas proposals abound as to what African governments should do in order to achieve these goals, those addressing how they might do so are rare. The literature still offers little guidance as to specific factors and processes that are likely to influence development and diffusion of agricultural technologies in given circumstances. This paper addresses the gap by analyzing the outcome of a multiyear, farmer-centred intervention to control trypanosomosis - a livestock disease transmitted by tsetse flies - carried out by the International Livestock Research Institute in southwest Ethiopia. While not conceived as such at the time, this intervention emerges, in retrospect, as a real world experiment in decentralized private provision of a traditional public extension activity. The nature of the control technology and several biophysical and socioeconomic characteristics of the region selected for control combined to produce a self-reinforcing process central to the success of the initiative. The intervention suggests that it is the demand side of agricultural extension systems that matters the most, and that in most cases, an organized articulation of demand will be required. The internal logic of that articulation is the exact reverse of that driving privatization and decentralization of extension systems. That logic also differs significantly from that guiding demand-led, farmer-participatory approaches to extension reform.
12893 Shaw, A.P.M., 2004. Economics of African trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 369-402.
Shaw: AP Consultants, Abbotts Ann, Andover, Hants SP11 7BA, UK.
Though the negative impact of human and animal trypanosomiasis was recognised early on, the economic study of the disease only became well established by the 1970s. Trypanosomiasis generates direct costs and indirect ones, but it may be difficult to formally separate these. Among the first are the costs arising from lessened livestock productivity, and the costs of control; indirect costs arise from limitations of production opportunities due to factors such as forced choice of breed, herd structure, animal traction, grazing patterns and migration. Trypanosomiasis being a rural disease has many social aspects relating to the affected population and the farming system in use at a given place, and analysis may be extremely complex. Economic quantification may rely heavily on assumptions involving prices, time effects, discounting, and control costs including numerous overheads. Regarding human African trypanosomiasis, there are many difficulties in the way of getting a clear picture, and hence a reliable economic analysis. These include disparity between actual and reported cases, which may be as much as 12 to 1. The concept of disability-adjusted life years (DALYs) applied to this disease as it occurs in southern Sudan and in Uganda is discussed. Greatly adding to the problems are the propensity of trypanosomiasis to break out quickly into large epidemics and its very high fatality rate. Patient care has a very high cost at the family level. The costs of controlling trypanosomiasis in humans are examined in terms of case detection, treatment, and vector control. Calculations of the cost of intervention in terms of DALYs averted indicated excellent justification for investment into HAT (gambiense) control. For the rhodesiense disease, the recent discovery that cattle can be an important animal reservoir has excellent implications for HAT control economics, as the costs of removing this reservoir by curing the cattle may pay for itself in terms of cattle productivity, even before considering direct benefits to human health. More studies are needed, and models of epidemiology and of economics have somehow to be integrated. Herd modelling has become an important technique. The broad picture of tsetse-transmitted trypanosomiasis in African livestock is presented. The direct impacts of the disease in livestock are covered, including mortality, calving rates, milk output, weight gain, draught animal work output, offtake and other parameters. Indirect effects of the disease in livestock are examined in terms of animal traction, choice of breed, herd size and structure, and migration. Costs of dealing with trypanosomiasis in livestock are analysed. Sections on tsetse control, use of trypanocides, the role of trypanotolerant livestock, and the study of farmers inputs cover a range of studies in different parts of the continent. Benefit-cost studies are often funded by a donor trying to decide on the feasibility or otherwise of a mooted development project; published data are few. Well-targeted tsetse control interventions usually realize high benefit-cost ratios. Higher-return projects are mainly on a local scale, and well focussed on farmers needs. At low livestock densities, using trypanocides is more cost-effective than tsetse control, but at higher densities the reverse may be true. Decisions regarding eradication of the vector as opposed to its control should turn on the true cost of elimination plus overheads, compared with the continuation of control measures for say 25 years. Other factors may come in, such as an anticipation of the lessening of the vector population due to spontaneous human settlement over a period of years. Economic analysis is about helping in decision making and guiding resource allocation. Much more data are available now than was the case in the past; the methods of intervention, the human population background, and local special features will always be changing and will require close monitoring and continued data collection.
12894 Butler, D. 2004. African labs win major role in tsetse-fly genome project. [News item] Nature, 427 (6973): 384.
12895 Canbäck, B., Tamas, I. & Andersson, S.G.E., 2004. A phylogenomic study of endosymbiotic bacteria. Molecular Biology and Evolution, 21 (6): 1110-1122.
Andersson: Department of Molecular Evolution, Evolutionary Biology Centre, University of Uppsala, Uppsala, Sweden. [[email protected]]
Endosymbiotic bacteria of aphids, Buchnera aphidicola, and of tsetse flies, Wigglesworthia glossinidia, are descendants of free-living g-Proteobacteria. The acceleration of sequence evolution in the endosymbiont genomes is here estimated from a phylogenomic analysis of the g-Proteobacteria. The tree topologies associated with the most highly conserved genes suggest that the endosymbionts form a sister group with Escherichia coli, Salmonella sp., and Yersinia pestis. Our results indicate that deviant tree topologies result from high substitution rates and biased nucleotide patterns, rather than from lateral gene transfer, as previously suggested. A reinvestigation of the relative rate increase in the endosymbiont genomes reveals variability among genes that correlate with host-associated metabolic dependencies. The conclusion is that host-level selection has retarded both the loss of genes and the acceleration of sequence evolution in endocellular symbionts.
12896 Dávila, A.M.R., Majiwa, P.A.O., Grisard, E.C., Aksoy, S. & Hide, W., 2004. [Response to Hertz-Fowler and Berriman, see 12898, below]: Continuing tsetse and Trypanosoma genome sequencing projects. Trends in Parasitology, 20 (7): 309-310.
Dávila: Departmento de Bioquímica e Biologia Molecular, Instituto Oswaldo Cruz, Fiocruz, Av. Brasil 4365, Rio de Janeiro, RJ 21045-900, Brazil. [[email protected]]
12897 Gooding R.H. & Krafsur E.S., 2004. Tsetse genetics: applications to biology and systematics. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 95-111.
Gooding: Department of Biological Sciences, University of Alberta, Edmonton, Canada.
The insights gained to date into the genetics of Glossina are described. Morphological mutants are extremely rare, but there is useful variation available at the level of chromosome structure. Allozymes and isozymes have been studied in representatives of all tsetse species groups, but require fresh or quick-frozen specimens to preserve enzyme activity. Microsatellite DNA sequences are useful for genetic work although sophisticated methods are needed for their study. Karyotypes and allozyme diversity of various tsetse species are described. Mutation rates are known to be very low. Rapid re-invasion rates and dispersal of tsetse might seem to point to high levels of genetic mixing, but allozyme diversities in a number of G. pallidipes populations appear to contradict this, indicating instead a clear population structuring and hence low average rates of gene flow. Mitochondrial genetic variation seen in G. morsitans and G. pallidipes give evidence of a recent population bottleneck, consistent with the historical tsetse distribution records from the time of the rinderpest epizootic in southern Africa. A hypothetical phylogenetic tree of tsetse species and subspecies is presented, with notes on the genetic information that has been used in its refinement. Unanswered questions concerning species status are indicated, and more extensive field sampling is called for. An attempt in the 1940s to control tsetse using the infertility arising from hybrid crosses is described. The greatly increased knowledge we now have of Glossina genetics (and of Glossina symbionts) has allowed new ideas for the control of the fly to emerge, and these are described.
12898 Hertz-Fowler, C. & Berriman, M., 2004. Continuing tsetse and Trypanosoma genome sequencing projects. Trends in Parasitology, 20 (7): 308-309.
Hertz-Fowler: Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Trypanosoma vivax and T. congolense have been sequenced to five-fold and three-fold coverage, respectively. Present knowledge of the better known T. brucei genome is assisting in building a framework for these other genomes. The reader is referred to; http://www.sanger.ac.uk/Projects/T_congolense; also http://www.sanger.ac.uk/Projects/Tvivax and http://www.genedb.org.
12899 Menjeta, M., Seal, N.J., Feldmann, U. & McCall, P.J., 2004. Mating competitiveness of irradiated Glossina austeni tsetse flies. Annals of Tropical Medicine and Parasitology, 98 (5): 539-542.
Seal: Department of Zoology, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, UK. [[email protected]]
Mating competitiveness of tsetse is regarded as critical in the possible application of SIT for the control of this disease vector. Tests were carried out on Glossina austeni comparing the mating characteristics of irradiated and non-irradiated males. It was concluded that in most of the aspects tested, irradiated males competed successfully with untreated males. The aspects included gaining copulations, transferring the same amount of sperm to females, time to initiating copulation and eliciting the same re-mating rejection in females. Irradiated males remain in copula for significantly longer than untreated males, however.
12900 Ogoyi, D.O., Achieng, D., Nguu, E.K. & Ochanda, J.O., 2003. Partial characterisation of a trypanosome-lysing factor from the midgut of the desert locust, Schistocerca gregaria. East African Medical Journal, 80 (11): 575-580.
Department of Biochemistry, College of Health Sciences, University of Nairobi, P.O. Box 30197, Nairobi, Kenya.
Lysis of isolated trypanosomes was demonstrated with midgut homogenates of natural vector Glossina morsitans centralis, as well as in non-vector insects. The highest trypanolytic activity was observed in midgut homogenate of the desert locust, S. gregaria followed by the cockroach, Periplaneta americana. Further studies on the S. gregaria trypanolytic factor showed its proteinaceous nature because of its sensitivity to temperatures above 40°C and to proteases. Additionally, the factor showed lectin-like properties since the activity was blocked by D-glucosamine. It is concluded that the trypanolytic factor has the potential of being used to modulate tsetse fly vectorial capacity.
12901 Terblanche, J.S., Klok, C.J. & Chown, S.L., 2004. Metabolic rate variation in Glossina pallidipes (Diptera: Glossinidae): gender, ageing and repeatability. Journal of Insect Physiology, 50 (5): 419-428.
Chown: Spatial, Physiological and Conservation Ecology Group, Department of Zoology, University of Stellenbosch, Private Bag X1, Matieland, Stellenbosch 7602, South Africa.
Despite the importance of metabolic rate in determining flight time of tsetse and in mediating the influence of abiotic variables on life history parameters (and hence abundance and distribution), metabolic rate measurements and their repeatability have not been widely assessed in these flies. We investigate age-related changes in standard metabolic rate (SMR) and its repeatability, using flow-through respirometry, for a variety of feeding, gender and pregnancy classes during early adult development in laboratory-reared individuals of the tsetse fly, Glossina pallidipes. Standard metabolic rate (144-635 mW) was generally within 22 percent of previous estimates, though lower than the values found using closed system respirometry. There was no significant difference between the genders, but metabolic rate increased consistently with age, probably owing to flight muscle development. Repeatability of metabolic rate measurement was generally high (r = 0.6-0.9), but not in younger teneral adults and pregnant females (r ˜ 0.05-0.4). In these individuals, low repeatability values are a consequence of muscle or in utero larval development. Tsetse and other flies generally have a much higher metabolic rate, for a given size, than do other insect species investigated to date.
12902 Ujváry, I. & Mikite, G., 2003. A practical synthesis of 3-n-propylphenol, a component of tsetse fly attractant blends. Organic Process Research and Development, 7 (4): 585-587.
Ujváry: Institute of Chemistry, Chemical Research Centre, Hungarian Academy of Sciences, PO Box 17, H-1525 Budapest, Hungary. [[email protected]]
A practical synthesis of the tsetse fly attractant 3-n-propylphenol involves the Grignard reaction of 3-hydroxybenzaldehyde and ethylmagnesium bromide affording a benzylic alcohol-type phenol derivative that upon catalytic hydrogenation gives the title product in 75 percent overall yield. Selection of the right solvent mixture and temperature range for the Grignard reaction is crucial for the kilogram-scale preparation of the target compound.
[See also 27: nos. 12922, 12924, 12927]
12903 Hargrove, J., 2004. Tsetse population dynamics. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 113-137.
Hargrove: 9, Monmouth Rd, Avondale, Harare, Zimbabwe. [[email protected]]
Population growth rates can be seen as the net balance resulting from an increase due to birth and immigration, and a decrease due to death and emigration. For tsetse, theory and field observations show that the time interval to the production of first larva, the time interval for the production of a later larva, and the duration of the inter-uterine larval period are strongly dependent on mean ambient temperature, although to understand better the effect of temperature the investigator should be aware that microhabitat conditions may be considerably different from ambient. Mortality is difficult to measure and it is not clear which factor is the most important, or if density-dependent effects help to regulate numbers. Mortality in utero is not thought to be of major importance. Pupal losses due to parasitism may be high and pupae are susceptible to high temperatures (e.g. 38°C). Teneral flies (i.e. recently emerged flies with low fat reserves and weakly developed thoracic muscles) are at greater risk than older flies, and under challenging climatic conditions small teneral flies are selectively eliminated. It is difficult to make mortality rate estimates of non-teneral adults for various reasons: mortality effects may well vary during the total life span of the adult; variable capture probability of flies frequently introduces a bias into the sample, affecting interpretation of results; and flies at a given site may not maintain a stable age distribution. These and other difficulties are discussed in detail. It is possible that tenerals are particularly prone to death from dryness, while the mature adults are more susceptible to temperature. Ignoring immigration, emigration and mortality, tsetse populations have the innate capacity to increase by a factor of 3500/year. Making reasonable assumptions for the pupal period and the interval to first and subsequent larvae, it can be shown that tsetse populations should nevertheless decline if subjected to mortality rates of c. 3.5 percent of females/day. Simple methods have been devised using traps and treated cattle to reach this mortality rate. Making some assumptions, a guide to the population growth rate of a G. m. morsitans population can be based on the prevailing mean temperature. The validity, limitations and potential of this approach are discussed. Dispersal rates of (savanna) flies are thought to be quite limited. Density-dependent mortality effects such as parasitism rates, as well as emigration rates, have some mainly indirect support as density-dependent variables, but their investigation presents great practical difficulties. A model that includes migration rates shows promise of becoming a powerful weapon in the design of control operations.
12904 Njiokou, F., Simo, G., Mbida Mbida, A., Truc, P., Cuny, G. & Herder, S., 2004. A study of host preference in tsetse flies using a modified heteroduplex PCR-based method. Acta Tropica, 91 (2): 117-120.
Njiokou: OCEAC, Laboratoire de Recherche sur les Trypanosomes, BP 288, Yaounde, Cameroon. [[email protected]]
A study of host preference in tsetse flies using a modified heteroduplex PCR-based method is described. Domestic and wild animal blood samples were collected to extract the corresponding reference DNAs. In Campo (south Cameroon), tsetse flies (mainly Glossina palpalis palpalis) were trapped and 41 bloodmeals were collected. All reference DNAs and 37 bloodmeal DNAs (90.7 percent) were successfully amplified and hybridized. Twelve bloodmeals (32.4 percent) were of human origin, 13 (35.4 percent) were from sitatunga antelope (Tragelaphus spekei) while 12 (32.4 percent) were not identified using our set of reference DNAs. The results confirmed the occurrence of frequent contacts between wild animals and this population of tsetse flies.
12905 Oyekunle, M.A., Talabi, A.O., Ojedokun, F.O. & Shittu, A.M., 2002. Dry season observation on dipterous flies in poultry facilities in Ogun State, Nigeria. [G. palpalis] Bulletin of Animal Health and Production in Africa, 50 (3): 194-197.
Oyekunle: Department of Animal Production, Olabisi Onabanjo University, Ago-Iwoye, Nigeria.
In a general survey of flies to be found in a battery and a deep litter chicken farm at a location in Nigeria, Glossina palpalis was found to be present in the deep litter system, not in the battery cage system. It was suggested that this might be because the deep litter house was near forest.
12906 Rogers, D.J. & Robinson T.P., 2004. Tsetse distribution. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 139-179.
Rogers: TALA Research Group, Department of Zoology, University of Oxford, Oxford, UK.
Early attempts at presenting the distribution of tsetse species on the continental scale are described. These attempts employed direct sampling records as well as inferences based on vegetation types. Remotely sensed satellite data have more recently become available, which in principle should help towards producing maps indicating habitats suitable for tsetse flies. The potential of remotely sensed satellite data is explained in terms of their spectra, temporal and spatial resolution. Data may be useable in their raw form, or processed in various ways to relate them to ground-based meteorological variables and indices such as land temperature, vegetation cover and the drying power of the atmosphere. There are two main approaches to modelling tsetse distribution: firstly the biological (predictive) one that searches the data for clues as to whether mortality rates can be inferred that would exclude the chance of the given species could exist in a particular area; and secondly, the statistical (descriptive) one, where the known distribution of flies is linked up to predictor indices derived from remote sensing which collectively will help to define the limits of species statistically, and hence be applicable on a very large geographical scale. The last is the method of choice for mapping tsetse distribution in this study. Thus the resulting maps give the distribution of conditions similar to those under which the given species of tsetse has been recorded in the past. An account of the methods used in data processing is given. Results, setting out the predicted areas of suitability for tsetse in Africa are given, according to species, and in some cases, subspecies. Maps are constructed that compare the predicted distribution, arising from the use of predictor indices, with the distribution as found using older classical methods. A dendrogram is set up to illustrate the relatedness of species according to their environmental preferences. The possibility that within-species taxonomic differences may come to light, and difficulties of ground sampling for populations present at low densities, are recognised. Technical improvements in remote sensing are anticipated.
12907 Zollner, G.E., Torr, S.J., Ammann, C. & Meixner, F.X., 2004. Dispersion of carbon dioxide plumes in African woodland: implications for host-finding by tsetse flies. Physiological Entomology, 29 (4): 381-394.
Torr: Natural Resources Institute, University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK. [[email protected]]
In Zimbabwe, high-resolution (10 Hz to an accuracy of ± 0.1 ppm) measurements were made of atmospheric and host-produced CO2 in tsetse habitats during the dry season. The diel structure of atmospheric CO2 concentrations is bimodal, with a minimum at approximately 16.00 hours and maxima at approximately 05.00 hours and 20.00 hours, respectively. The background CO2 noise is greater in densely vegetated riverine woodland than in leafless, deciduous (mopane) woodland. Variation in atmospheric CO2 concentrations is correlated with decreasing wind speed and increasing thermal stability. Consequently, the background noise during the day is greatest in riverine woodland during early morning and late afternoon, when winds are typically light and stable, and thermal inversion conditions are developing. Measurements were made of CO2 at 8-64 m downwind from natural (two cattle) or synthetic sources (4-20 litres min-1 CO2). The signal from the sources appears as fluctuations above threshold (approximately 355-362 ppm), in the form of intermittent bursts of CO2. The strength, duration and intermittency of the signals attributable to these sources declines with source strength and distance from the source. In riverine woodland, approximately 50 percent of all bursts are 0.1 s long, and 10 percent are > 2.0 s long. Carbon dioxide signals from equivalent sources are stronger in riverine woodland than mopane. Carbon dioxide dispensed at rates of 4-20 litres min-1 is detected up to 64 m downwind of the source but peaks are typically <10 ppm above threshold. Consequently, host-CO2 signals are obscured during periods of large fluctuations in atmospheric CO2. These results suggest that CO2 is detectable, at least in some circumstances, at tens of metres downwind and hence dispel the notion that its action is limited to that of a short-range attractant.
12908 Allsopp, R. & Hursey, B.H., 2004. Insecticidal control of tsetse. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 491-507.
Allsopp: Albany, Western Australia.
Two chemical groups have been widely used in tsetse control: the organochlorines (DDT, dieldrin, endosulfan) and the synthetic pyrethroids. DDT is cheap, has low mammalian toxicity, is effective against tsetse and has a long persistence. Both DDT and dieldrin eventually fell victims to international bans due to fears about their environmental effects. Deltamethrin has been the main pyrethroid used due to its great toxicity to tsetse. Delivery methods for insecticidal attack of tsetse has taken three main forms: depositing residual insecticide discriminatively on to the resting and breeding sites of tsetse by ground spraying or less selectively from the air; repeated spraying of non-residual insecticide over large areas using aircraft (sequential aerosol technique: SAT); and attracting tsetse to treated surfaces (artificial and live-bait techniques). A number of campaigns using teams of knapsack sprayers, tractor mounted machines, the sequential aerosol technique and thermal fogging are described. Formulations and dosages are given for the main delivery methods, with costs. Environmental concerns and the results of environmental studies into the effects of insecticide use against tsetse are reviewed. Looking to the future, it is noted that whereas short term control often results from insecticidal campaigns, in the longer term such gains are frequently lost to reinvasion. A large scale programme (Regional Tsetse and Trypanosomiasis Control Programme) to co-ordinate an attack on the common fly belt spanning four countries was clearly focussed and technically sound, but issues of cost, environmental impact, and perceptions about the importance of community participation led to the demise of ground spraying and the SAT, greatly restricting the technical options. New initiatives by AU and endorsement by PAAT envision a programme to eliminate tsetse flies from some 9 million km2 of Africa, and recommend the pivotal use of the sterile insect technique. This technique cannot stand alone and will require to be used in conjunction with some of the chemical control methods already described, especially discriminative ground spraying and SAT.
12909 Belete, H., Tikubet, G., Petros, B., Oyibo, W.A. & Otigbuo, I.N., 2004. Control of human African trypanosomiasis: trap and odour preference of tsetse flies (Glossina morsitans submorsitans) in the upper Didessa river valley of Ethiopia. Tropical Medicine and International Health, 9 (6): 710-714.
Oyibo: Department of Microbiology, Immunology and Parasitology, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia. [[email protected]]
Ethiopia is one of the endemic countries for Human African Trypanosomiasis (HAT) as over 100 000 people are at risk of having the disease. The control of HAT using odour preference of tsetse flies (Glossina morsitans submorsitans) was studied in upper Didessa river valley of Ethiopia. No information exists on the effectiveness of attractants for this species of tsetse flies in Ethiopia. Three attractants and their combinations namely: acetone, octenol, cow urine, acetone + octenol, acetone + octenol + cow urine, were evaluated using biconical and NGU traps for their efficacy as a first step in developing a sustainable community-based HAT control initiative. The biconical traps baited with acetone, octenol or cow urine, or when combined, were more effective in catching G. m. submorsitans than the NGU traps. However, the NGU traps caught more female tsetse flies than the biconical traps. The acetone, octenol and cow urine combination was the most effective in attracting tsetse flies in both the biconical and NGU traps. Acetone was the best attractant while octenol was the least effective. Cow urine showed great promise for possible use in community-based HAT control activities, especially urine that has been kept for several days. The use of cow urine in HAT control in Ethiopia is likely to succeed in the future because of the sustainability of its supply.
12910 Dransfield R.D. & Brightwell, R., 2004. Community participation in tsetse control: the principles, potential and practice. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 533-546.
Dransfield: InfluentialPoints.com, Burwash, East Sussex, UK.
The article focuses on the farmer/community-based approach to countering the problems posed by trypanosomiasis; the rationale is that chemotherapy will be the main way to control the disease in low challenge areas, but that farmers should themselves use vector control in high-challenge areas. Conflicting perceptions of the value of the community-based approach are mentioned. Many different degrees of community participation and control over events can be found in the field, and have been described in the literature. Ways of encouraging participation may include public meetings, distribution of publicity material, farm visits by extension workers, more formal Participatory Rural Appraisal techniques, and drama; the net result should be greater community education and mobilization, sometimes involving group formation and encouraging local ownership of the project or of its components. It can be very difficult to hand over a project to local control if the project has been centrally planned and funded from the start. In practice, community action may be seen as a way of saving costs, for example by getting the villagers to contribute their labour, rather than as a full commitment to community involvement. A great variety of forms taken by community participation is to be expected, given the diversity on the ground regarding social structure, farming methods, local needs and aspirations, and the acuteness of the disease problem. Accurate description of difficulties faced by the community approach is essential; the large scale of action needed especially against savanna tsetse is one such constraint, as cohesive social forces may not be in place. Farmers have little liquid capital and costs of local intervention programmes may be too expensive; sufficient know-how and training may be lacking. Generally speaking, the commitment to get essential changes in attitudes towards community participation is low and needs to be increased.
12911 Feldmann, U., 2004. The sterile insect technique as a component of area-wide integrated pest management of tsetse. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 565-582.
Feldmann: Insect Pest Control Section, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, Vienna, Austria. [[email protected]]
The integrated pest management (IPM) concept aims at intervention in pest control situations in such a way that benefits are optimised, while undesired effects (such as on the environment) are minimized. Integration of a variety of control measures is looked for. Area-wide (AW) applications have to take into account variations in the ability or willingness of smallholders to take part. Generally, a wide, uniform suppressive measure will have greater effect than a higher level of suppression that misses out a significant part of the target population on the ground. The sterile insect technique (SIT) aims at releasing reproductively sterile insects within the wild target population on the ground, the release being maintained over several generations. While the costs of colony rearing, sterilization and release of the colony individuals in large numbers can be high, savings accrue from decreased use of insecticides or other control methods. For tsetse, the focus is usually on the release of large numbers of sterilized males into a wild pest population, and repeating the release until the native population is eliminated. Pilot trials against Glossina have been conducted at Lake Kariba, Zimbabwe (vs G. morsitans morsitans), at Tanga, Tanzania (vs G. m. morsitans), in Burkina Faso (vs G. palpalis gambiensis, G. tachinoides, and G. m. submorsitans), in Plateau State, Nigeria; and in Zanzibar, Tanzania (vs G. austeni). Operational details are given in each case, with problems met with and the degree of success attained estimated. Plans for applying AW SIT to parts of Ethiopia are at an advanced stage, with facilities for rearing flies already in place. Lessons learned from the successful use of SIT against the New World screwworm fly and fruit flies such as the medfly are described. The various parameters involved in feasibility of the SIT are explored, taking note especially of the slow reproductive rate of tsetse and the slow rate of re-infestation. Environmental benefits from tsetse control, and in particular from use of the SIT concept, are enumerated. Economic feasibility of SIT is greater in the area-wide approach. It is suggested that the real issue is whether the initial funding for such a campaign can be raised. Operational details of the production, distribution and release of competitive but sterile males are explained. Monitoring of the wild and released tsetse populations will be critical, and monitoring sites at key points will allow this. The future prospects for tsetse control by the SIT are discussed, with special reference to political aspects, and how likely improvements in GIS and in our understanding of genetics and molecular biology could well assist in reaching the overall objectives.
12912 Hargrove, J. 2002. Tsetse eradication: necessity, sufficiency and desirability. Available as pdf file in Tsetse control: the next 100 years. Report of meeting organised by the DFID Animal Health Programme, 9-10 September 2002, Edinburgh, UK.
Hargrove: 9 Monmouth Rd, Avondale, Harare, Zimbabwe. [[email protected]]
Regarding the mechanisms of tsetse eradication, we may look back to the time before we had any insecticides. Potts and Jackson worked in an experimental area amounting to 600 square miles of country and organized hunters to shoot everything the size of an impala or bigger. Total game destruction was shown to be a sufficient method for eradicating closed populations of tsetse but Potts and Jackson thought it neither necessary nor desirable because bush clearing was, in the long run, cheaper and more effective. Nagupande in the Western part of Zimbabwe was the site of a field experiment in which only four game animal species were shot: warthog, bushpig, bushbuck and kudu. Good control of tsetse was achieved but it was regarded as being insufficient for eradication, quite regardless of the desirability of the method. A ground-spraying trial with DDT was started and the results were so impressive that ground spraying became for a time the mainstay of tsetse control in that part of the country; however to achieve eradication it was found necessary and financially worthwhile to use selective hunting as well. Attention then turned to the use of traps, a much improved method environmentally, but reinvasion remains a recurring problem. Modelling shows that if a control campaign such as aerial spraying over an area of 16 000 km2 leaves 16 flies behind, then unless there is a very high natural mortality rate operating eradication of the fly will not result. Detecting the last few flies is in practice extremely difficult. The question thus arises: does SIT therefore have special merit to be included in the arsenal of control methods? Concerning ecological arguments, if you remove tsetse flies from an area you change the ecological balance and we have to be very sure in our own minds that the resulting land use change is going to be favourable. It is not always clear that clearing the land for cattle and crops is actually the best route. Issues such as aid for tsetse eradication have to be closely linked to the issues of human rights and good governance. [See also notice under Section A - News.]
12913 Maniania, N.K., Laveissière, C., Odulaja, A., Ekesi, S. & Herren, H.R., 2003. Entomopathogenic fungi as potential biocontrol agents for tsetse flies. Advances in microbial control of insect pests, 2003, pp. 145-163. Kluwer Academic/Plenum Publishers; New York, USA.
Maniania: International Centre of Insect Physiology and Ecology (ICIPE), P.O. Box 30772, Nyayo Stadium, Nairobi, Kenya.
This review covers the potential of entomopathogenic fungi for the control of tsetse flies. A list of fungal pathogens reported from Glossina is given. The nature of the insect-fungus interaction is described, including adhesion and germination of the fungal spore, penetration of the host integument, and intra-haemocoelic development of the fungus. The factors affecting the efficacy of fungi as biocontrol agents are described, including the virulence of the pathogenic population, the reaction and susceptibility of the host population, and environmental factors (temperature, moisture and solar radiation). Application strategies are described, with details given of the design of laboratory infectivity bioassays and of field delivery systems. Field suppression trials are described and the prospects of using an inoculation device for tsetse control discussed. A brief note is given on the effect of fungal pathogens on non-target organisms. In conclusion, the authors believe that more research will bring a major move forward in realizing some of the potential of this control method.
12914 OHanlon, L.H., 2004. Tinkering with genes to fight insect-borne disease. Lancet, 363 (9417): 1288-1289.
Genetic engineering techniques could be applied to vectors such as mosquitoes, tsetse flies and reduviid bugs to provide entirely new ways of combating the transmission of some vector-borne diseases. One strategy would be to release insects homozygous for a lethal dominant into the wild. Factory stock used for breeding the insects for later release would be protected by supplying a vital nutrient not available in the general environment. A related method would insert a gene that could selectively kill female progeny but spare the males; the latter would survive to propagate the gene to successive generations. An alternative approach seeks to make the wild population refractory to the transmission of human pathogens: using genetically engineered bacterial symbionts might allow a way to do this.
12915 Vale, G.A. & Torr, S.J., 2004. Development of bait technology to control tsetse. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 509-523.
Vale: Mount Pleasant, Harare, Zimbabwe. [[email protected]]
The potential of bait technology for the control of tsetse was appreciated even in the first half of the 20th century, but the method appeared to have less to offer than game destruction, bush clearing or the widespread use of insecticides. The ecological damage that these latter methods caused became clearer by the 1970s and use of baits, both live and artificial, became more attractive by comparison. The research strategy then was to improve bait design by the careful analysis of basic responses of tsetse to baits, and using the knowledge to improve the design of devices used in the field; further, the optimum density, siting and management of baits were analysed. Basic findings at this stage were that catches from live baits were heavily biased; electrocuting devices (wire grids) gave a much clearer idea than did hand-netting and trapping of the tsetse population near to baits; host odour was much more important as an attractant than had been recognized; and that many tsetse attracted to baits failed to enter into the nearby traps. Odours act more from a distance, but colour and shape are more effective at shorter range. Detailed analysis of odour pinpointed the following tsetse attractants emanating from cattle: carbon dioxide, acetone, butanone, octenol (1-octen-3-ol), 4-methyl phenol and 3-n-propyl phenol. Several of these were used to enhance the attractiveness of baits. Trapping technology gained new impetus in the 1970s from empirical work against palpalis group flies in West Africa. Many designs of traps were tried out in the field, often using phthalogen blue and black cloth; effectiveness varied according to which species was being sampled, and, surprisingly, to the geographical area. Traps could be used for control as well as for monitoring the population, but in the case of morsitans group flies attention veered to the use of greatly simplified, odour-baited, insecticide-treated screens (targets) rather than more elaborate traps. Calculations based on effectiveness of different baits can produce guidelines for their placement and density; bait densities required for a given rate of population decline or for setting up a tsetse barrier line can be calculated from the data given. Insecticide treated cattle can act as very effective baits; it is particularly cost-effective if cattle are already being dipped against ticks so that the only extra cost involved in tsetse control is the marginal one of using pyrethroids instead of the standard acaricide chemicals. Improved traps and bait technology (targets) rapidly become the standard control method throughout much of tsetse infested Africa in the late 1980s and the 1990s. Some of the possible pitfalls in the application of bait technology are given. These include trying to tackle too small an area, and costs and benefits relating to community-based action can be very variable according to circumstances. Nevertheless, tailoring the bait programme to local needs is often feasible and bait technology may be easier to integrate with local control of flies by the community, than would be the case for other centrally planned and operated campaigns. Further research lines are indicated, especially regarding insecticide-treated cattle, and the possible adverse effects of insecticide in cattle dung. Route and rates of tsetse reinvasion need to be closely studied.
12916 Van den Bossche P. & De Deken R., 2004. The application of bait technology to control tsetse. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 525-532.
van den Bossche: Department of Veterinary Medicine, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium. [[email protected]]
After a slow start, bait technology has become recognised as an integral part of the arsenal of tsetse control methods. The factors determining the effectiveness of baits for tsetse control are discussed. Expansion of the human population with their cattle may lead to interaction with tsetse, leading to a switch of tsetse feeding on wild hosts to greater dependence on cattle; the epidemiological implications of this switch depend on the relative numbers of wild hosts and of cattle. When cattle are at low density, artificial baits can be used to control the fly and to reduce trypanosomiasis even though the tsetse may not be eliminated. At higher cattle densities and where tsetse are forced to take a larger proportion of feeds from cattle, insecticide-treated cattle may be more effective than stationary baits. According to local conditions, a combination of stationary baits and treated cattle may be appropriate. Effective barriers to reinvasion may require treated screens (targets) deployed in a band 6-8 km deep; even untreated traps set up in high density may prevent reinvasion by riverine tsetse in West Africa. When planning the use of treated cattle, allowance for relatively uneven distribution of herds under village-style husbandry should be made. Some undesirable side effects of tick control using pyrethroids are discussed.
12917 Coleman, P.G. & Welburn, S.C., 2004. Are fitness costs associated with resistance to human serum in Trypanosoma brucei rhodesiense? Trends in Parasitology, 20 (7): 311-315.
Welburn: Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Roslin, Midlothian, EH25 9RG, UK. [[email protected]]
A causative agent of sleeping sickness, Trypanosoma brucei rhodesiense, is differentiated from the morphologically identical parasite of animals Trypanosoma brucei brucei by its ability to infect humans. Epidemiological theory predicts that where these two subspecies coexist, the prevalence in non-humans of T. b. rhodesiense will exceed that of T. b. brucei. However, field observations suggest that the opposite is true, with T. b. brucei predominating. Here, we hypothesize that this discrepancy between theory and observations results from a reduction in fitness of T. b. rhodesiense relative to T. b. brucei when outside humans. The hypothesis is sufficient to reconcile theoretical predictions with field observations, and is consistent both with experimental data on parasite maturation probabilities in tsetse and growth rates in non-human serum. Further experiments to elucidate possible fitness costs of human-serum resistance could have significant implications for T. b. rhodesiense control.
12918 Eisler, M.C., Dwinger R.H., Majiwa, P.A.O. & Picozzi K., 2004. Diagnosis and epidemiology of African animal trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 253-267.
Eisler: Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, UK.
This account of the methods of diagnosis of animal trypanosomiasis opens with a reminder that the work may have to be carried out under the most adverse physical and economic conditions. Given that, farmers may have to rely on clinical diagnosis, even though such signs are not specific for the disease. Parasitological diagnosis may be through blood films with or without concentration techniques, and these are described. More at the research level, sub-inoculation methods may be useful, including animal sub-inoculation, xenodiagnosis and in vitro culture. The promise and limitations of various methods of immunological diagnosis are discussed, with reference to complement fixation test, indirect fluorescent antibody test, card-agglutination trypanosomiasis test, and various forms of enzyme-linked immunosorbent assay (ELISA). The practical, economic and administrative problems of getting some of these newer techniques evaluated and available for field use are described. Molecular methods of diagnosis based on the detection and amplification of nucleic acids show promise. These are considered under the heads of species-specific diagnosis, multiple species detection, and epidemiological applications. DNA-based diagnostics have great potential in epidemiological studies. Other genetic methodologies are described. For the future, it should be kept in mind that although technical improvements will make molecular and other sophisticated methods of diagnosis easier to apply in the field, the extreme conditions under which farmers and veterinary assistants work will ensure that clinical diagnosis has continued importance: for instance, a means to inexpensive haemoglobin determination would be very helpful to field workers.
12919 Fèvre, E.M., Coleman, P.G., Welburn, S.C. & Maudlin, I., 2004. Reanalyzing the 1900-1920 sleeping sickness epidemic in Uganda. Emerging Infectious Diseases, 10 (4): 567-573.
Fèvre: Centre for Tropical Veterinary Medicine, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK. [[email protected]]
Sleeping sickness has long been a major public health problem in Uganda. From 1900 to 1920, more than 250 000 people died in an epidemic that affected the southern part of the country, particularly the Busoga region. The epidemic has traditionally been ascribed to Trypanosoma brucei gambiense, a parasite now confined to central and western Africa. The Busoga region still reports sleeping sickness, although it is caused by T. b. rhodesiense, commonly believed to have spread to Uganda from Zambia in the 1940s. Our analysis of clinical data recorded in the early 1900s shows that the clinical course of sleeping sickness cases during the 1900-1920 epidemic in Uganda was markedly different from T. b. gambiense cases, but similar to T. b. rhodesiense. These findings suggest that T. b. rhodesiense was present in Uganda and contributed to the epidemic. The historic context is reassessed in the light of these data.
12920 Hall, M.J.R. & Wall, R., 2004. Biting flies: their role in the mechanical transmission of trypanosomes to livestock and methods for their control. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 583-594.
Hall: Department of Entomology, The Natural History Museum, Cromwell Road, London.
Attention is drawn to the ability of some blood-sucking flies to transmit trypanosomes from an infected host animal to an uninfected one, directly, not involving cyclical development in the vector. This is termed mechanical transmission. While in tsetse infested country it can be difficult to prove that mechanical transmission occurs, in tsetse-free areas the evidence is unambiguous. Trypanosoma evansi (possibly originating from T. brucei) is mechanically transmitted by biting flies in Asia and in Central and South America. Trypanosoma vivax occurs in Mauritius and Latin America, where the biting flies are probably responsible for transmission. Some strains of T. vivax have become incapable of being transmitted by tsetse. Instances of field and laboratory or artificial environment non-cyclical transmission of trypanosomes are described; control options versus Stomoxys and tabanids are discussed against this background. However, it is concluded that there is no unequivocal evidence that mechanical transmission of the pathogenic trypanosomes occurs by means of non-tsetse biting flies in the tsetse belts of Africa.
12921 Hide, G. & Tait A., 2004. Genetics and molecular epidemiology of trypanosomes. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 77-93.
Hide: Centre for Parasitology, Molecular Epidemiology and Ecology, Biosciences Research Institute, School of Environment and Life Sciences, University of Salford, Salford, UK.
The study of molecular epidemiology, defined as the application of molecular biological methods to the investigation of the epidemiology of the disease, has become an important factor in trypanosomiasis investigations since the 1980s. It uses molecular markers of taxonomic units, so that parasites can be tracked through different hosts, through various geographical areas, and into the diverse associations between disease and parasites. The relative genetic stability or otherwise of the main target organisms has to be understood, if valid conclusions are to come from such research. The range of tools available is reviewed, covering multilocus enzyme electrophoresis, DNA hybridization with its different applications, and PCR detection of parasites. Different tools may have their greatest efficiency at different taxonomic levels: the level of genus, species, subspecies or even lower. Molecular tools have revealed subdivision of T. b. gambiense populations, providing valuable hints as to the epidemiological status of these different populations; and different foci of Rhodesian sleeping sickness have yielded strains of T. b. rhodesiense that owe their human infectivity to quite separate gene mutations, suggesting that human infective trypanosomes in East Africa have arisen at least twice. This epidemiological model is being developed. The implications for formal taxonomy of the T. brucei s.s. are touched upon. Trypanosoma congolense and T. simiae are placed in a separate sub-genus from T. brucei; several sub-populations or groups of T. congolense isolates have been distinguished by DNA probes. The process of integrating classical epidemiological methods with those of molecular epidemiology has started, but more has to be done. Most effort in the latter field has been spent on species definition, methods of field sample analysis, and population genetic analysis. The present review examines two epidemics in Uganda, the Busoga epidemic and the Soroti epidemic. One general outcome to these integrated studies has been the realization that cattle are potential animal reservoirs of human infective strains of T. brucei. This finding creates an important new model by which the persistence of foci may be better understood, as well as suggesting new methods of intervention. Future research lines are indicated.
12922 Laveissière, C. & Grébaut, P., 2003. Risk index of sleeping sickness transmission: simplification of the calculation. Insect Science and its Application, 23 (2): 99-102.
Laveissière: OCEAC, BP 288, Yaoundé, Cameroon.
To simplify and improve the effectiveness of human trypanosomiasis control efforts as well as reduce their cost, it is desirable to identify high-risk sites for transmission of trypanosomes by tsetse flies to humans. The authors propose a simplification of the risk index previously developed by Laveissière et al. (1994). The simplified index has been developed in Côte dIvoire and validated in Cameroon. Unlike the old index which required determination of the flies daily survival rate, the calculation of this new index requires only the knowledge of the proportions of teneral flies and of flies that have fed on human blood, from the population caught in the various biotopes.
12923 Luckins A.G. & Dwinger, R.H., 2004. Non-tsetse-transmitted animal trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 269-281.
Luckins: Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, UK.
This account is mainly concerned with the two species, Trypanosoma evansi and T. vivax and deals with their epidemiology, distribution, phylogenetic relationships and molecular characterization, how the infections are transmitted, the diagnosis of infection, control of the diseases, and their economic impact. The emphasis is on the diseases caused in Central and South America, and in Asia, but there is also some reference to the role of T. evansi in Africa. A comprehensive reference section will be useful to those coming to the topic for the first time.
12924 Mahama, C.I., Desquesnes, M., Dia, M.L., Losson, B., de Deken, R. & Geerts, S., 2004. A cross-sectional epidemiological survey of bovine trypanosomosis and its vectors in the Savelugu and West Mamprusi districts of northern Ghana. Veterinary Parasitology, 122 (1): 1-13.
Geerts: Department of Parasitology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium. [[email protected]]
The epidemiology of bovine trypanosomosis was investigated in two districts (Savelugu and West Mamprusi) of Northern Ghana with different land use and environmental characteristics. The land use intensity and environmental change was suspected to be higher in the Savelugu District. A cross-sectional entomological survey conducted along the White Volta river and its tributaries confirmed the presence of only Glossina palpalis gambiensis and G. tachinoides. The challenge index as measured by the product of tsetse density and tsetse infection rate was much higher in the West Mamprusi (19.6) than in the Savelugu district (4.7). A total of 1 013 cattle (508 in Savelugu and 505 in West Mamprusi) were bled from a random selection of 16 villages in the Savelugu District and 13 villages in the West Mamprusi District. Blood samples were examined for trypanosomes by the buffy coat technique (BCT). Blood samples that were positive in the BCT or negative in the BCT but with packed cell volume (PCV) values below 21 were further tested with a polymerase chain reaction for trypanosomal DNA. Plasma samples of all cattle were serologically tested with an indirect ELISA for trypanosomal antibodies. The parasitological and serological prevalence of bovine trypanosomoses was significantly higher in West Mamprusi (16 and 53 percent, respectively) than in Savelugu District (8 and 24 percent, respectively). An evaluation of animal health at the village herd level, using PCV as an index of anaemia, provided various epidemiological scenarios prevalent in the entire study-area.
12925 Nagamune, K., Acosta-Serrano, A., Uemura, H., Brun, R., Kunz-Renggli, C., Maeda, Y., Ferguson, M.A.J. & Kinoshita, T., 2004. Surface sialic acids taken from the host allow trypanosome survival in tsetse fly vectors. Journal of Experimental Medicine, 199 (10): 1445-1450.
Kinoshita: Department of Immunoregulation, Research Institute for Microbial Disease, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. [[email protected]]
The African trypanosome Trypanosoma brucei, which causes sleeping sickness in humans and Nagana disease in livestock, is spread via blood-sucking tsetse flies. In the flys intestine, the trypanosomes survive digestive and trypanocidal environments, proliferate, and translocate into the salivary gland, where they become infectious to the next mammalian host. Here, we show that for successful survival in tsetse flies, the trypanosomes use trans-sialidase to transfer sialic acids that they cannot synthesize from hosts glycoconjugates to the glycosylphosphatidylinositols (GPIs), which are abundantly expressed on their surface. Trypanosomes lacking sialic acids due to a defective generation of GPI-anchored trans-sialidase could not survive in the intestine, but regained the ability to survive when sialylated by means of soluble trans-sialidase. Thus, surface sialic acids appear to protect the parasites from the digestive and trypanocidal environments in the midgut of tsetse flies.
12926 Njiokou, F., Nkinin, S.W., Grébaut, P., Penchenier, L., Barnabé, C., Tibayrenc, M. & Herder, S., 2004. An isoenzyme survey of Trypanosoma brucei s.l. from the Central African subregion: population structure, taxonomic and epidemiological considerations. Parasitology, 128 (6): 645-653.
Njiokou: OCEAC, BP 288, Yaoundé, Cameroon. [[email protected]]
In order to improve our knowledge about the taxonomic status and the population structure of the causative agent of Human African Trypanosomiasis in the Central African subregion, 169 newly isolated stocks, of which 16 came from pigs, and 5 reference stocks, were characterized by multilocus enzyme electrophoresis, for 17 genetic loci. We identified 22 different isoenzyme profiles or zymodemes, many of which showed limited differences between them. These zymodemes were equated to multilocus genotypes. UPGMA dendrograms revealed one main group, Trypanosoma brucei gambiense group I, and three T. brucei non-gambiense stocks. Trypanosoma b. gambiense group I zymodemes were very homogenous, grouping all the human stocks and 31 percent of the pig stocks. Two main zymodemes (Z1 and Z3) grouping 74 percent of the stocks were found in different remote countries. The genetic distances were relatively high in T. brucei non-gambiense zymodemes, regrouping 69 percent of pig stocks. The analysis of linkage disequilibrium was in favour of a predominantly clonal population structure. This was supported by the ubiquitous occurrence of the main zymodemes, suggesting genetic stability in time and space of this parasites natural clones. However, in some cases an epidemic population structure could not be ruled out. Our study also suggested that the domestic pig was a probable reservoir host for T. b. gambiense group I in Cameroon.
12927 Njiru, Z.K., Makumi, J.N., Okoth, S., Ndungu, J.M. & Gibson, W.C., 2004. Identification of trypanosomes in Glossina pallidipes and G. longipennis in Kenya. Infection, Genetics and Evolution, 4 (1): 29-35.
Njiru: Kenya Trypanosomiasis Research Institute (KETRI), P.O. Box 362, Kikuyu, Kenya. [[email protected]]
The polymerase chain reaction (PCR) was used to identify trypanosomes in Glossina pallidipes and G. longipennis caught in Kenya. Of 3 826 flies dissected, 188 (4.9 percent) were parasitologically positive overall. The infection rate in G. pallidipes was 5.7 percent (187 of 3 301 flies), but only one of 525 G. longipennis was infected (infection rate 0.2 percent). There was a higher infection rate in female G. pallidipes flies than in male flies. The infected flies were analyzed by PCR using 10 sets of primers specific for species and subgroups within the subgenera Nannomonas, Trypanozoon and Duttonella. Of 188 parasitologically positive samples, PCR identified 137 (72.9 percent), leaving 51 (27.1 percent) non-identified. We recorded infection rates of 47.2 percent for Trypanosoma congolense savannah, forest and kilifi subgroups, 20.9 percent for T. simiae/T. simiae Tsavo/T. godfreyi, 14.9 percent for T. brucei ssp. and 13.8 percent for T. vivax. Thirty-nine (26.7 percent) flies had mixed infections, with a minor association between T. congolense savannah/T. simiae Tsavo/T. godfreyi. The relative proportion of each trypanosome species or subgroup varied between fly belts with T. congolense (all subgroups) being the most abundant and T. godfreyi the least. Statistical analysis showed that the dissection method and the PCR test classified infections independently. This study shows that pathogenic trypanosomes are widespread in all sampled tsetse fly belts with G. pallidipes as the main vector. Furthermore, the PCR test is more reliable in detecting and identifying trypanosomes than is the dissection method.
12928 Njiru, Z.K., Ndungu, K., Matete, G., Ndungu, J.M. & Gibson, W.C., 2004. Detection of Trypanosoma brucei rhodesiense in animals from sleeping sickness foci in East Africa using the serum resistance associated (SRA) gene. Acta Tropica, 90 (3): 249-254.
Njiru: Kenya Trypanosomiasis Research Institute (KETRI), P.O. Box 362, Kikuyu, Kenya. [[email protected]]
The human serum resistance associated (SRA) gene has been found exclusively in Trypanosoma brucei rhodesiense, allowing the unequivocal detection of this pathogen in reservoir hosts and the tsetse vector without recourse to laborious strain characterization procedures. We investigated the presence of the SRA gene in 264 T. brucei ssp. isolates from humans, domestic animals and Glossina pallidipes from foci of human trypanosomiasis in Kenya and Uganda. The SRA gene was present in all isolates that were resistant to human serum, and absent from all serum sensitive isolates tested. Further, the gene was present in all isolates that had previously been shown to be identical to human infective trypanosomes by isoenzyme characterization. The SRA gene was detected in isolates from cattle, sheep, pigs, dog, reedbuck, hyena and G. pallidipes from sleeping sickness foci, but was not found in Trypanosoma evansi or in Trypanosoma brucei gambiense isolates. The present study indicates that the SRA gene may be invaluable in detecting and differentiating T. brucei rhodesiense from other T. brucei ssp. in reservoir hosts and tsetse.
12929 Odiit, M., Coleman, P.G., McDermott, J.J., Fèvre, E.M., Welburn, S.C. & Woolhouse, M.E.J., 2004. Spatial and temporal risk factors for the early detection of Trypanosoma brucei rhodesiense sleeping sickness patients in Tororo and Busia districts, Uganda. Transactions of the Royal Society of Tropical Medicine and Hygiene, 98 (10): 569-576.
Odiit: Sleeping Sickness Programme, POB 96, Tororo, Uganda. [[email protected]]
We have carried out a study of risk factors for early detection of Trypanosoma brucei rhodesiense sleeping sickness. Records of sleeping sickness patients from 1987 to 2001 from Tororo and Busia districts in Uganda were reviewed for their village of origin and clinical stage (early or late). All villages that reported sleeping sickness and fixed post-diagnostic sleeping sickness health units in Tororo and Busia districts were geo-referenced. The spatial distribution of early and late stage patient detection by health units was analysed using Geographical Information Systems (GIS). Of 1 316 sleeping sickness patients admitted at the Livestock Health Research Institute and Busolwe hospitals and Lumino health centre from Tororo and Busia districts, 471 (35.8 percent) were early stage, 825 (62.7 percent) were late stage, while 20 (1.5 percent) were not staged. Five hundred and eighty-five (44.5 percent) came from within a 10 km radius of the reporting health units. After multivariate analysis, the proportion of early stage patients detected was found to be significantly associated with patients originating from within a 10 km radius of the health unit, with adults (> 19 years), and with annual parish incidence. Application of GIS and the early to late stages ratio are an informative and powerful means of determining efficiency of surveillance of sleeping sickness.
12930 Ravel, S., Grébaut, P., Mariani, C., Jamonneau, V., Cuisance, D., Gooding, R.H. & Cuny, G., 2004. Monitoring the susceptibility of Glossina palpalis gambiensis and G. morsitans morsitans to experimental infection with savannah-type Trypanosoma congolense, using the polymerase chain reaction. Annals of Tropical Medicine and Parasitology, 98 (1): 29-36.
Ravel: IRD, UR035, Laboratoire de Recherche et de Coordination sur les Trypanosomoses IRD-CIRAD, TA 207/G, Campus International de Baillarguet, 34398 Montpellier Cedex 5, France. [[email protected]]
Teneral Glossina palpalis gambiensis and G. morsitans morsitans were fed on mice infected with savannah-type Trypanosoma (Nannomonas) congolense. The infection was monitored by checking the postfeeding diuresis fluid (midgut infection) and saliva (mature infection) of individual flies for parasites, at different times postinfection, using microscopical examination and a PCR-based assay. The results indicated that both tsetse species supported established midgut infections by 10 days postinfection and that maturation occurred after 24 days in G. m. morsitans. Although, for both diuresis fluid and saliva, the results of the microscopy showed good concordance with those of the PCR, the PCR identified more positive samples. Monitoring allowed determination of the status of the infection in individual flies, which was confirmed, 48 days postinfection, by the microscopical examination of the midguts and probosces dissected out of the flies and by the PCR-based amplification of any trypanosome DNA in these organs. Again, in terms of the detection of trypanosomes in the dissected organs, there was good concordance between the results of the PCR and those of the microscopy, although PCR revealed many more mature infections than did microscopical examination, particularly in the G. p. gambiensis investigated. There was a higher prevalence of immature infection in G. p. gambiensis than in G. m. morsitans but the interspecific differences seen in the prevalences of any infection and of mature infection were not statistically significant. The intrinsic vectorial capacity for T. congolense of both tsetse species therefore appeared quite similar, although the true vectorial competence of G. p. gambiensis remains to be determined.
12931 Ravel, S., Mariani, C., Grébaut, P., Jamonneau, V., Cuisance, D. & Cuny, G., 2004. Inhibition of the DNA amplification of trypanosomes present in tsetse flies midguts: Implications for the identification of trypanosome species in wild tsetse flies. Parasite, 11 (1): 107-109.
Ravel: Laboratoire de Recherche et de Coordination sur les Trypanosomoses, UR035 IRD-CIRAD, Programme Santé Animale, TA 207/G, Campus International de Baillarguet, 34398 Montpellier Cedex 5, France.
The present study was carried out to investigate the cause of a failure of PCR in identifying parasitologically positive tsetse flies in the field, in a proportion of cases. Tsetse flies (Glossina palpalis gambiensis and G. morsitans) were experimentally infected with two different species of Trypanosoma (T. brucei gambiense and T. congolense). A total of 152 tsetse flies were dissected and the organs of each fly (midgut, proboscis and salivary glands) were examined. The parasitologically positive organs were then analysed using PCR. Results showed that, regardless of the trypanosome species, PCR failed to amplify 40 percent of the parasitologically positive midguts. This failure, which does not occur with diluted samples, is likely to be caused by an inhibition of the amplification reaction. This finding has important implications for the detection and the identification of trypanosome species in wild tsetse flies.
12932 Solano, P., Kone, A., Garcia, A., Sane, B., Michel, V., Michel, J.F., Coulibaly, B., Jamonneau, V., Kaba, D., Dupont, S. & Fournet, F., 2003. Role of patient travelling in transmission of human African trypanosomosis in a highly endemic area of Côte dIvoire. Médecine Tropicale, 63 (6): 577-582.
Solano: LRCT IRD/CIRAD Campus de Baillarguet TA 207G, 34398 Montpellier Cedex 5, France. [[email protected]]
Human African trypanosomosis (HAT) remains a major public health problem in sub-Saharan Africa. The region around the town of Bonon in west-central Côte dIvoire is a highly endemic HAT zone. The purpose of this study was to assess the role of travelling of infected patients in the transmission of HAT. The study population included a total of 96 patients in whom HAT had been diagnosed actively or passively between 1999 and 2000. Information on each patients residence and workplaces, i.e. water site, and farm field, was used to calculate the mean distance travelled and mean number of places visited daily by each patient. Findings indicated that both parameters, i.e., distance travelled and number of places visited, were significantly higher for patients living in Bonon than those living in hamlets or homesteads. Based on analysis of patient movements the endemic zone could be divided into three subdivisions with different modes of disease transmission. This study was performed as a preliminary step for a larger investigation designed to allow specific targeting of HAT hot spots based mainly on a geographic information system.
12933 Steketee, R.W., 2003. Pregnancy, nutrition and parasitic diseases. Journal of Nutrition, 133 (5 Supplement 2): 1661S-1667S.
Steketee: Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. [[email protected]]
In the developing world, young women, pregnant women and their infants and children frequently experience a cycle where undernutrition (macronutrient and micronutrient) and repeated infection, including parasitic infections, lead to adverse consequences that can continue from one generation to the next. Among parasitic infections, malaria and intestinal helminths coexist widely with micronutrient deficiencies and contribute significantly to anaemia and this cycle of retarded growth and development. In somewhat more limited or focal geographical settings, other parasitic diseases (e.g., schistosomiasis, filariasis and African trypanosomiasis) contribute similarly to this cycle. It is undoubtedly much better to enter a pregnancy free of infection and nutritionally replete than the various alternatives. Existing intervention strategies for micronutrient support and for the control of common parasitic infections before or during pregnancy, particularly malaria and intestinal helminths, should be followed. However, further research to identify barriers and priority approaches to achieving this goal remain very important in resource-poor settings where targeted public health efforts are required.
12934 Sutherst, R.W., 2004. Global change and human vulnerability to vector-borne diseases. Clinical Microbiology Reviews, 17 (1): 136-173.
Sutherst: CSIRO Entomology, Long Pocket Laboratories, 120 Meiers Rd, Indooroopilly, Queensland 4068, Australia. [[email protected]]
Global climate changes have seen atmospheric CO2 concentration increase by almost one third, and the concentration of methane double. Such changes are not known to affect vector-borne diseases directly, but may do indirectly. For example, under warmer conditions plants produce more foliage with the same amount of water, other nutrients allowing. This may provide more favourable microclimates for insect vectors and increase the duration of those seasons for which they persist; also water reservoirs may form more readily, suitable for mosquito breeding. The studies of climate change as it affects Glossina are touched upon; also the changing degree and nature of contact between infective Trypanosoma and man in Africa.
12935 van den Bossche, P., de Deken, R., Brandt, J., Seibou, B. & Geerts, S., 2004. Recirculation of Trypanosoma brucei brucei in cattle after T. congolense challenge by tsetse flies. Veterinary Parasitology, 121 (1-2): 79-85.
van den Bossche: Department of Veterinary Medicine, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium. [[email protected]]
The effect of challenging cattle, chronically infected with Trypanosoma brucei brucei, with T. congolense on the development of the T. b. brucei infection was investigated. For this purpose, nine experimental animals were first infected with T. b. brucei through the bites of infected tsetse flies. Once the T. b. brucei had developed into a chronic infection, that was difficult to detect using routine parasitological diagnostic tools, seven of the experimental animals were challenged by tsetse flies infected with T. congolense. Two of the animals infected with T. b. brucei were kept as control. The infection with T. congolense resulted in a sudden increase in the parasitaemia of T. b. brucei. In the T. b. brucei control animals, on the other hand, the parasitaemia remained below the level of detection. The epidemiological repercussions of this increase in the parasitaemia of T. b. brucei after infection with T. congolense are discussed.
12936 Welburn S.C., Fèvre E.M., Coleman P.G. & Maudlin I., 2004. Epidemiology of human African trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 219-232.
Welburn: Centre for Tropical Veterinary Medicine, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Roslin, Midlothian, EH25 9RG, UK. [[email protected]]
There were devastating epidemics of human African trypanosomiasis at the end of the 19th century, and the current levels of cases indicate a very serious resurgence of the disease over the low levels seen in the 1960s. Historically, the causes of the disease have been sought in terms of socio-economic changes to the human population, particularly those brought about by the colonial impact. Lacking the quantitative information or the appropriate research tools, progress in epidemiological studies was limited. However, basic understanding of the cause of the disease (the blood parasite Trypanosoma brucei s.l.) and of the fly vector (Glossina) was quickly gained, and the value of case finding and cure appreciated. Trypanosoma brucei exists in three forms, all morphologically indistinguishable: T. b. brucei, which is like the others an animal parasite but is non-infective to humans; T. b. rhodesiense which causes the more acute Rhodesian sleeping sickness in man in eastern and southern Africa; and T. b. gambiense causing Gambian sleeping sickness as found in mainly central and western Africa, and which develops over several years in the human host. The virulence of the Rhodesian form of the disease is now attributed to the evolution of a gene for human serum resistance (SRA gene), and at the molecular biology level the presence of this gene can be used to distinguish between T. b. brucei and T. b. rhodesiense. This genetic variant may have evolved more than once. There is no direct evidence of any heritable human immunity to T. b. rhodesiense. While population movements associated with the colonial era may have been in part responsible for the massive outbreaks of sleeping sickness of the late 19th century, we do not know if earlier population changes, as in the Bantu migration from West Africa into Central Africa, and later to much of southern Africa, also generated similar outbreaks. Both forms of the disease occur in Uganda, with T. b. gambiense affecting the northwest and T. b. rhodesiense present in the southeast. Originally both foci were thought to be due to T. b. gambiense, but improved technology has allowed better identification of the causative organisms, and has drawn attention to the importance of persistent foci rather than to the spread of the disease from far away, in such cases. While suspected from early on, the importance of animal reservoirs for T. b. rhodesiense has been confirmed using modern techniques. The bushbuck was the first wild animal to be so identified, and was followed by others; but more recently cattle have been shown to act as reservoirs, epidemiologically an especially important finding. The importance of animal reservoirs in Gambian sleeping sickness epidemiology is less clear, and is probably much less important. Various models of sleeping sickness epidemiology have been attempted, involving the infective status of the patients, the presence/absence of an animal reservoir, case finding and treatment, and control of the vector. These allow a more rational choice as to preferred intervention strategies. It might one day be possible to identify which cattle are carrying T. b. rhodesiense and treat these, so reducing epidemiological risk. Climate will also have an effect, not least through the changes induced on the vector habitat, and GIS techniques as well as data from greatly improved fly trapping methods are being brought to bear on modelling.
12937 Büscher P. & Lejon, V., 2004. Diagnosis of human African trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 203-218.
Büscher: Unit of Parasite Diagnostics, Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium.
Diagnosis of human African trypanosomiasis is defined as the demonstration of infection by Trypanosoma brucei gambiense or T. b. rhodesiense. Demonstration may be direct, by observation of the parasite itself, or indirect, using clinical, serological and molecular test results. Tests should also show whether the disease has progressed to involve the CNS, as this will affect the treatment chosen. Diagnosis and treatment is particularly important in this progressively debilitating disease; also, since it is a sickness that affects rural communities, to counter it countermeasures should be cost-effective, rapid and simple, and sound diagnostic performance is vital. The clinical signs associated with the initial and haemolymphatic stage are outlined, including chancre, fever and general malaise, adenopathy, skin rash and pruritus, local oedema, cardiovascular disturbances, endocrine dysfunction, and even neurological disorders. As the disease progresses, nervous system involvement become more obvious: these are clinical signs associated with the meningoencephalitic stage: disturbances of consciousness and sleep; disorder of tonus, motility and abnormal movements; and mental changes including psychiatric problems. Parasitological diagnosis is important because treatment is itself hazardous; methods used cover chancre aspiration, lymph node aspiration, and examination of the cerebrospinal fluid and of the blood. Various tests on blood can be conducted: wet blood film, thick blood film, microhaematocrit centrifugation technique, quantitative buffy coat, mini anion exchange centrifugation technique, in vitro culture, and (normally under research conditions only) xenodiagnosis. Serological diagnosis now covers a rich variety of tests, including immunofluorescence assay, ELISA, immune trypanolysis, CATT/T. b. gambiense, procyclic agglutination test for trypanosomiasis, haemagglutination (infrequently used now), LATEX/T. b. gambiense, and card indirect agglutination test for trypanosomiasis. Molecular diagnosis is still under development, and is used at a research level; false positives and negatives are still generated at present. The importance of stage determination and follow-up are emphasised, having regard to the chance of relapse, but under field conditions the re-examination of treated patients can be very difficult. Techniques of detecting trypanosomes in the cerebrospinal fluid are described, and the use of white blood cell count, total protein concentration, detection of trypanosome-specific antibody, and levels of various other constituents in the cerebrospinal fluid evaluated. A simplified algorithm (flow chart) for sleeping sickness diagnosis is presented.
12938 Hotez, P.J., Remme, J.H.F., Buss, P., Alleyne, G., Morel, C. & Breman, J.G., 2004. Combating tropical infectious diseases: report of the Disease Control Priorities in Developing Countries Project. Clinical Infectious Diseases, 38 (6): 871-878.
Breman: Fogarty International Center, National Institute of Health, Building 16, Room 214, 16 Center Drive, MSC 6705, Bethesda, MD 26892, USA. [[email protected]]
Infectious diseases are responsible for >25 percent of the global disease toll. The new Disease Control Priorities in Developing Countries Project (DCPP) aims to decrease the burden of these diseases by producing science-based analyses from demographic, epidemiologic, disease intervention, and economic evidence for the purpose of defining disease priorities and implementing control measures. The DCPP recently reviewed selected tropical infectious diseases, examined successful control experiences, and defined previously unsettled patient treatment, prevention, and research issues. Disease elimination programs against American trypanosomiasis (Chagas disease), onchocerciasis, lymphatic filariasis, leprosy, trachoma, and measles are succeeding. Dengue, leishmaniasis, African trypanosomiasis, malaria, diarrhoeal diseases, helminthic infections and tuberculosis have reemerged because of inadequate interventions and control strategies and the breakdown of health delivery systems. Application of technologies must be cost-effective and intensified research is essential if these and other scourges are to be controlled or eliminated in the 21st century.
12939 Odiit, M., Shaw, A., Welburn, S.C., Fèvre, E.M., Coleman, P.G. & McDermott, J.J., 2004. Assessing the patterns of health-seeking behaviour and awareness among sleeping-sickness patients in eastern Uganda. Annals of Tropical Medicine and Parasitology, 98 (4): 339-348.
Odiit: Sleeping Sickness Programme, LIRI Hospital, PO Box 96, Tororo, Uganda. [[email protected]]
For those with sleeping sickness, the consequences of delayed diagnosis include poor prognosis at treatment and an increased risk of tsetse infection. Data on their socio-demographic and clinical characteristics, health-seeking behaviour and delays in presentation and diagnosis were collected from 119 diagnosed cases of rhodesiense sleeping sickness in eastern Uganda. The median total delay, from onset of the illness to diagnosis, was 60 days. The median service-provider delay (30 days) was markedly longer than the median patient delay (17 days). Each of these delays was, however, considerable and independently associated with patients presenting with late-stage sleeping sickness. A blood examination at the first visit was also associated with the service-provider delay. Most of the patients (77.4 percent) had either been referred to the local sleeping sickness hospital by other members of their community or presented at the hospital on their own initiative; few had been referred by other components of the local health system. The results are disappointing, not only in showing long delays in diagnosis (and therefore in treatment) but also in indicating that much of the delay is attributable to the service provider failing to diagnose sleeping sickness among symptomatic individuals.
12940 Papadopoulos, M.C., Abel, P.M., Agranoff, D., Stich, A., Tarelli, E., Bell, B.A., Planche, T., Loosemore, A., Samira Saadoun, Wilkins, P. & Sanjeev Krishna, 2004. A novel and accurate diagnostic test for human African trypanosomiasis. Lancet, 363 (9418): 1358-1363. [see also 12962, below]
Krishna: Department of Cellular and Molecular Sciences, St Georges Hospital Medical School, London SW17 0RE, UK. [[email protected]]
Human African trypanosomiasis (sleeping sickness) affects up to half a million people every year in sub-Saharan Africa. Because current diagnostic tests for the disease have low accuracy, we sought to develop a novel test that could diagnose human African trypanosomiasis with high sensitivity and specificity. We applied serum samples from 85 patients with African trypanosomiasis and 146 control patients, in the UK, who had other parasitic and non-parasitic infections, to a weak cation exchange chip and analysed with surface-enhanced laser desorption-ionization time-of-flight mass spectrometry. Mass spectra were then assessed with three powerful data-mining tools: a tree classifier, a neural network, and a genetic algorithm. Using the results, spectra (2-100 kDa) were grouped into training (n = 122) and testing (n = 109) sets. The training set enabled data-mining software to identify distinct serum proteomic signatures characteristic of human African trypanosomiasis among 206 protein clusters. Sensitivity and specificity, determined with the testing set, were 100 percent and 98.6 percent, respectively, when the majority opinion of the three algorithms was considered. This novel approach is much more accurate than any other diagnostic test. This report of the accurate diagnosis of an infection by use of proteomic signature analysis could form the basis for diagnostic tests for the disease, monitoring of response to treatment, and improving the accuracy of patient recruitment in large-scale epidemiological studies.
12941 Robays, J., Bilengue, M.M.C., van der Stuyft, P. & Boelaert, M., 2004. The effectiveness of active population screening and treatment for sleeping sickness control in the Democratic Republic of Congo. Tropical Medicine and International Health, 9 (5): 542-550.
Robays: Epidemiology Unit, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium. [[email protected]]
The human African trypanosomiasis (HAT) control programme of the Democratic Republic of Congo (DRC) uses mass screening with the card agglutination test for trypanosomes (CATT). We looked at the contribution of CATT and improved parasitological confirmation to the effectiveness of screening and treatment. The effectiveness of the screening and treatment process is measured by the percentage of HAT cases that is effectively cured after a single round of screening. The process is analysed in five steps: (i) the attendance at the screening, (ii) the sensitivity of the screening procedure, (iii) the sensitivity of the parasitological confirmation, (iv) the proportion of the confirmed cases that effectively receive treatment and (v) the cure rate of the treatment. We used a simplified model that multiplies proportions of infected persons that go through each step. We estimated these parameters using a combination of routine data collected by the national control programme over the period January 1997 to December 1998 and published data. For varying attendance rates we compared the effectiveness of screening strategies based on CATT or on CATT combined with improved parasitological confirmation by mini anion exchange column technique (mAECT) with the previously used strategy based on palpation of neck glands and microscopy alone. The model shows that overall effectiveness of the active case detection and treatment strategy is <50 percent under most scenarios. Attendance rates averaged 74 percent but showed considerable regional variability and are a major problem in some areas of DRC. The CATT and replacing traditional parasitology by mAECT increases the sensitivity of the screening but a substantial part of the gains are lost at other stages of the screening process. Improvements of the HAT screening process such as introduction of CATT or mAECT only make sense if other parameters and attendance rate in particular are optimized at the same time.
12942 Robays, J., Kadima, A.E., Lutumba, P., Bilenge, C.M.M., Mesu, V.K.B.K., De Deken, R., Makabuza, J., Deguerry, M., Van der Stuyft, P. & Boelaert, M., 2004. Human African trypanosomiasis amongst urban residents in Kinshasa: a case-control study. Tropical Medicine and International Health, 9 (8): 869-875.
Robays: Epidemiology Unit, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium. [[email protected]]
Increasing numbers of human African trypanosomiasis (HAT) cases have been reported in urban residents of Kinshasa, Democratic Republic Congo since 1996. We set up a case-control study to identify risk factors for the disease. All residents of the urban part of Kinshasa with parasitologically confirmed HAT and presenting for treatment to the city's specialized HAT clinics between 1 August, 2002 and 28 February, 2003 were included as cases. We defined the urban part as the area with contiguous habitation and a population density >5 000 inhabitants per square kilometre. A digital map of the area was drawn based on a satellite image. For each case, two serologically negative controls were selected, matched on age, sex and neighbourhood. Logistic regression models were fitted to control for confounding. The following risk factors were independently associated with HAT: travel, commerce and cultivating fields in Bandundu, and commerce and cultivating fields in the rural part of Kinshasa. No association with activities in the city itself was found. In 2002, the emergence of HAT in urban residents of Kinshasa appears mainly linked to disease transmission in Bandundu and rural Kinshasa. We recommend to intensify control of these foci, to target HAT screening in urban residents to people with contact with these foci, to increase awareness of HAT amongst health workers in the urban health structures and to strengthen disease surveillance.
12943 Truc, P., Lekane Likeufack, C., Mbongo, N. & Eboo Enyenga, V., 2004. A procedure for isolating and freezing metacyclic Trypanosoma brucei gambiense forms in the field. Acta Tropica, 90 (2): 219-221.
Truc: Institut de Recherche pour le Développement, UR35 Trypanosomoses Africaines, OCEAC, POB 288, Yaounde, Cameroon. [[email protected], [email protected]]
An adaptation of a modified procedure using anion-exchange centrifugation was evaluated to isolate and freeze in field conditions a large number of bloodstream forms of Trypanosoma brucei gambiense for direct in vitro culture. Pellets of trypanosomes were obtained from 62 patients in Central Africa. The presence of trypanosomes was detected in all 62 eluates. The isolation system was efficient. Preliminary results of in vitro culture of ten thawed samples of trypanosomes were very promising as no fungal or bacterial contamination was noticed even after two weeks of culture.
12944 Enanga, B., Burchmore, R.J.S., Stewart, M.L. and Barrett, M.P., 2002. Sleeping sickness and the brain. Cellular and Molecular Life Sciences, 59 (5): 845-858.
Barrett: Institute of Biomedical and Life Sciences, Division of Infection and Immunity, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK. [[email protected]]
Recent progress in understanding the neuropathological mechanisms of sleeping sickness reveals a complex relationship between the trypanosome parasite that causes this disease and the host nervous system. The pathology of late-stage sleeping sickness, in which the central nervous system is involved, is complicated and is associated with disturbances in the circadian rhythm of sleep. The blood-brain barrier, which separates circulating blood from the central nervous system, regulates the flow of materials to and from the brain. During the course of disease, the integrity of the blood-brain barrier is compromised. Dysfunction of the nervous system may be exacerbated by factors of trypanosomal origin or by host responses to parasites. Microscopic examination of cerebrospinal fluid remains the best way to confirm late-stage sleeping sickness, but this necessitates a risky lumbar puncture. Most drugs, including many trypanocides, do not cross the blood-brain barrier efficiently. Improved diagnostic and therapeutic approaches are thus urgently required. The latter might benefit from approaches which manipulate the blood-brain barrier to enhance permeability or to limit drug efflux. This review summarizes our current understanding of the neurological aspects of sleeping sickness, and envisages new research into blood-brain barrier models that are necessary to understand the interactions between trypanosomes and drugs active against them within the host nervous system.
12945 Jamonneau, V., Ravel, S., Garcia, A., Koffi, M., Truc, P., Laveissière, C., Herder, S., Grébaut, P., Cuny, G. & Solano, P., 2004. Characterization of Trypanosoma brucei s.l. infecting asymptomatic sleeping-sickness patients in Côte dIvoire: a new genetic group? Annals of Tropical Medicine and Parasitology, 98 (4): 329-337.
Jamonneau: Centre Pierre Richet, BP 1500, Bouaké, Côte dIvoire. [[email protected]]
Six villagers in the Sinfra focus of sleeping sickness in Côte dIvoire who in 1995 were asymptomatic and refusing treatment, despite then being serologically and parasitologically positive for trypanosomes, were followed up, while still refusing treatment, until 2002. In 2002, five of the six cases remained serologically positive but no trypanosomes could be found in any of them by use of the classical parasitological methods. A PCR-based assay, however, revealed that all six had the DNA of Trypanosoma brucei s.l. in their blood, so confirming the low sensitivity of the classical parasitological tests. The analysis of satellite, minisatellite and microsatellite markers indicated that, in 2002, all six cases were infected with a new distinct genetic group of T. brucei s.l. and four were co-infected with T. b. gambiense group 1. The epidemiological consequences of such co-infections are discussed. The new group of T. brucei had a molecular pattern that differed from those of the classical T. b. gambiense group 1 and the bouaflé group.
12946 Kirrstetter, M., Lerin-Lozano, C., Heintz, H., Manegold, C., Gross, W.L. & Lamprecht, P., 2004. Trypanosomiasis in a woman from Cameroon mimicking systemic lupus erythematosus. Deutsche Medizinische Wochenschrift, 129 (23): 1315-1317.
Kirrstetter: Poliklinik für Rheumatologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Rheumaklinik Bad Bramstedt, Ratzeburger Allee 160, 25358 Lübeck, Germany.
A 27-year-old woman from Cameroon was admitted because of arthralgia, myalgia and severe thrombocytopenia (20 000/ml). She had been suffering from weakness, recurrent febrile episodes, generalized lymphadenopathy and pancytopenia for two years. Having a typical autoantibody constellation and fulfilling four of the American College of Rheumatology (ACR) classification criteria, systemic lupus erythematosus (SLE) had been diagnosed at another hospital. Treatment with corticosteroids and azathioprine did not improve her condition. A number of abnormal laboratory findings were obtained. Examination of peripheral blood smears disclosed Trypanosoma brucei infection. After the diagnosis of stage 2 West African trypanosomiasis (sleeping sickness) specific treatment was initiated leading to subsequent remission of the disease. This case report underlines the importance of a thorough differential diagnosis in cases of suspected autoimmune disease. Induction of autoantibodies during infectious diseases may be misleading. The use of the ACR criteria for SLE must be restricted to the classification of proven connective tissue diseases.
12947 Mamani-Matsuda, M., Rambert, J., Malvy, D., Lejoly-Boisseau, H., Daulouede, S., Thiolat, D., Coves, S., Courtois, P., Vincendeau, P. & Mossalayi, M.D., 2004. Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages. Antimicrobial Agents and Chemotherapy, 48 (3): 924-929.
Mamani-Matsuda: Laboratoire dImmunologie et de Parasitologie, Faculté de Pharmacie, Université Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. [[email protected]]
In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)- a and nitric oxide derivatives. In the present study, quercetin (3,3',4',5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-a and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.
12948 Na-Bangchang, K., Doua, F., Konsil, J., Hanpitakpong, W., Kamanikom, B. & Kuzoe, F., 2004. The pharmacokinetics of eflornithine (a-difluoromethylornithine) in patients with late-stage T. b. gambiense sleeping sickness. European Journal of Clinical Pharmacology, 60 (4): 269-278.
Na-Bangchang: Faculty of Allied Health Sciences, Thammasat University, Pathumtanee, Thailand. [[email protected]]
It was concluded that oral eflornithine (DFMO) at the dose of 125 mg/kg body weight given every 6 h for 14 days may not produce adequate therapeutic plasma and CSF levels for patients with late-stage T. b. gambiense sleeping sickness. Detailed methods and results are given supporting this conclusion.
12949 Noël, W., Raes, G., Ghassabeh, G.H., Baetselier, P. de & Beschin, A., 2004. Alternatively activated macrophages during parasite infections. Trends in Parasitology, 20 (3): 126-133.
Beschin: Department of Cellular and Molecular Interactions, Flemish Interuniversity Institute for Biotechnology, Free University of Brussels (VIB-VUB), Building E, Floor 8, Pleinlaan 2, B-1050 Brussels, Belgium.
Functions of macrophages exposed to cytokines from T helper cells type 2 (Th2) have an immunological role that is poorly known in comparison with classically activated macrophages. The possible role of alternatively activated macrophages in response to various parasitic diseases including trypanosomiasis is discussed.
12950 Pentreath V.W. & Kennedy G.E., 2004. Pathogenesis of human African trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 283-301.
Pentreath: School of Environment and Life Sciences, Salford University, Salford, UK.
The distinction between Trypanosoma brucei rhodesiense and T. b. gambiense, and respectively the acute and chronic forms of sleeping sickness they cause, is useful, but these are to be seen as extremes along a continuum of somewhat similar pathological conditions. One distinction is that Rhodesian sleeping sickness may lead to death in months from damage to the heart or viscera, while the Gambian forms are chronic with involvement of the CNS and intercurrent infections. The first stages of infection include the establishment of the parasite in lymphatics, blood and other systems; later stages involve damage to the CNS, with increases in the white blood cell count, protein levels and parasites in the CSF. Such different pathologies require different treatments. A chancre or nodule appears at the site of an infective tsetse bite. The features of the chancre are described. Lymph glands swell as the parasites multiply within them; in Gambian sleeping sickness swollen neck glands are a useful sign. Lymph glands can be a useful source of parasites for diagnosis. Waves of parasitaemia follow, with fevers; the pathological effect of these invasive waves on the composition of the blood is described. Effects of infection on the spleen, heart and blood vessels, skin, skeletal muscles, eyes and intestines are described. Various endocrine dysfunctions can result, perhaps caused by parasite invasion of different endocrine glands; other symptoms appear to arise from dysfunction of the circadian pacemaker. The problems inherent in transferring laboratory findings using rodents to the human case, are emphasised. Nevertheless, much useful information has come from animal studies, concerning autoantibodies, immune complexes, cytokines, mediators, and immunosuppression. The progressive neuropathology is also described, covering data arising from neuroradiology and electroencephalography, morphological changes, the composition of CSF and CNS damage; the results of animal model experiments are described in some detail. Drug treatment of the late-stage disease may trigger post-treatment reactive encephalopathy; here again animal models have been helpful, but the usual caution is needed in interpreting the results in terms of the human disease. The substances initiating pathogenesis may be the breakdown products of dead or inactivated trypanosomes, substances released by the living parasite, or substances from the host body released in response to the infection. Sorting out these influences, which may act in concert, or with one form setting off another, has proved to be difficult.
12951 Pfaff, A.W. & Candolfi, E., 2003. Immune responses to protozoan parasites and its relevance to diagnosis in immunocompromised patients. [T. brucei] European Journal of Protistology, 39 (4): 428-434.
Pfaff: Institut de Parasitologie et Pathologie Tropicale, 3 rue Koeberlé, 67000 Strasbourg, France. [[email protected]]
Many species of different protozoan groups spend all or parts of their life cycles as parasites within vertebrate hosts, including humans. The host response and the parasites escape strategies (including Trypanosoma brucei) are discussed. Depending on the parasites life cycle, severity of the disease and kinetics of dissemination, different diagnostic methods are applied. Once established, the different parasite species have a remarkable ability to suppress and/or divert the hosts immune response so that the infection will ultimately be controlled and tolerated, but not eliminated. This delicate equilibrium is easily disturbed by concomitant infections or immunosuppressive treatment. In the case of HIV infection, some of these protozoan parasitic infections, notably toxoplasmosis, cryptosporidiosis and visceral leishmaniasis, will develop as opportunistic infections with an often fatal outcome. However, this aggravation is not observed in infections with Plasmodium or Trypanosoma. These complex modifications of the hosts immune response by a concomitant infection or immunosuppressive treatment dramatically change the physiopathology, while having no effect on serological and PCR diagnostic results. This demands novel diagnostic tools which are more appropriate for these situations.
12952 Vanhamme, L., Renauld, H., Lecordier, L., Poelvoorde, P., Van Den Abbeele, J. & Pays, E., 2004. The Trypanosoma brucei reference strain TREU927/4 contains T. brucei rhodesiense-specific SRA sequences, but displays a distinct phenotype of relative resistance to human serum. Molecular and Biochemical Parasitology, 135 (1): 39-47.
Pays: Laboratory of Molecular Parasitology, Department of Molecular Biology, IBMM, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B-6041 Gosselies, Belgium. [[email protected]]
12953 Wilson, M.E. & Chen, L.H., 2004. Dermatologic infectious diseases in inter-national travelers. Current Infectious Disease Reports, 6 (1): 54-62.
Wilson: Division of Infectious Diseases, 330 Mt. Auburn Street, Mount Auburn Hospital, Cambridge MA, 02238 USA.
Skin lesions provide an important clue to the diagnoses of many infections in returned travellers. New information related to epidemiology, recognition, diagnosis, or management is described for the systemic infections - dengue fever, several of the rickettsial infections, African trypanosomiasis, and coccidioidomycosis. Many pathogens cause focal skin lesions. Recent findings are presented for cutaneous leishmaniasis, Buruli ulcer, gnathostomiasis, cutaneous larva migrans, myiasis, tungiasis, and scabies. This paper describes the most common skin problems in returning travellers and outlines the types of infections that cause skin lesions, as defined by morphologic characteristics.
12954 Barrett, M.P., Coombs G.H. & Mottram J.C., 2004. Future prospects in chemotherapy for trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 445-460.
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.
New drugs are urgently needed for the treatment of trypanosomiasis. Problems with the present array of available drugs are listed, including drug resistance and toxic side effects. Generic forms of variable efficacy and formulations below claimed levels lead to ideal conditions for resistance to develop. Poor infrastructure and political upheavals add to the difficulties of maintaining desired standards of use. The ways in which the drugs must pass through various biological barriers within the body add to the stringent attributes required of a potential new candidate compound. The modes of action of drugs and drug-resistance mechanisms are reviewed. Biochemical pathways traced in trypanosomes offer the means of selecting targets to attack. Such areas are glucose metabolism and the glycosome, thiol metabolism and oxidant stress, polyamine metabolism, nucleotide metabolism and purine salvage, lipid and sterol metabolism; cell signalling and differentiation; protein degradation and amino acid metabolism; membrane architecture; the kinetoplast, RNA editing and regulation of gene expression. Some trypanocides under development are described. Combination chemotherapy and new formulation for old drugs are assessed; evidence of some synergy should be followed up. The great knowledge of trypanosome biochemistry and genetics that has built up has yet to be translated into progress on the pharmaceutical front. It would be a great advantage if new drugs for human use could be orally administered. Further study of the blood-brain barrier, including in vitro models, would greatly assist the search for new effective compounds.
12955 Burri, C., Stich, A. & Brun, R., 2004. Current chemotherapy of human African trypanosomiasis. In The Trypanosomiases (eds. I. Maudlin, P.H. Holmes & M.A. Miles) CABI Publishing, 2004, pp. 403-419.
Burri: Swiss Tropical Institute, Swiss Centre for International Health Pharmaceutical Medicine Unit, Basel, Switzerland.
This deals with the administration and use of the drugs currently applied to the treatment of human African trypanosomiasis. The following registered drugs are described: pentamidine, suramin, melarsoprol and eflornithine; non-registered drugs described are nifurtimox, and diminazene aceturate (Berenil®). Each account is given detailed treatment as regards clinical application, pharmacology, and availability and costs. Pentamidine and suramin are registered for treatment of the first stage of the disease; melarsoprol and eflornithine are registered for treatment of the second, neurological, phase. A chart is presented comparing selected treatment schedules used for late-stage sleeping sickness with melarsoprol, 1949-2000.
12956 Louis, F.J., Keiser, J., Simarro, P.P., Schmid, C. & Jannin, J., 2003. Léflornithine dans le traitement de la maladie du sommeil. [Eflornithine for the treatment of sleeping sickness.] Médecine Tropicale, 63 (6): 559-562.
Louis: OMS CDS/CPE/ZFK. BP 155 Yaoundé, Cameroon. [[email protected]]
The use of eflornithine to treat sleeping sickness is described. The chemical structure, mode of action, dosages and secondary effects are outlined. Clinical use of the drug is reviewed.
12957 Mansour, T.E., 2002. Chemotherapeutic targets in parasites: contemporary strategies, 2002, pp. 226. Cambridge University Press.
Mansour: Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Of particular interest is Chapter 5 (pp. 90-128), Antitrypanosomal and antileishmanial targets, which covers trypanothione and trypanothione reductase in Protozoa; the tryparedoxins; the antiprotozoal effects of Nifurtimox; the polyamines and ornithine decarboxylase; glycolysis as a target for antitrypanosomal agents; mitochondrial DNA as a target for antitrypanosomal agents; purine and pyrimadine metabolism as targets; antigenic variation in African trypanosomes and the design of antiparasitic agents; protein farnesylation as a drug target; and cystein proteases as targets for antitrypanosomal and antileishmanial agents.