12485
Reid R.S., Thornton P.K., & Kruska R.L., 2001. Livestock disease control and the changing landscapes of South-west Ethiopia, in Agricultural technologies and tropical deforestation (eds Angelsen, A. & Kaimowitz. D.), 271-290.
See extended summary in Section A of TTIQ 26 (1).
12486
De la Rocque, S., Geoffroy, B., Michel, J.F., Borne, F., Solano, P., Meunier, J.Y. & Cuisance, D., 2002. Tsetse flies wings, an identity card of the insect? Parasite, 9 (3): 275-281.
De la Rocque: CIRAD-EMVT, Campus de Baillarguet, BP 5035, 34032 Montpellier, France. [[email protected]]
The size of tsetse flies is often associated with population dynamics and vectorial capacity parameters. Adult fly size is generally estimated from measurements of wing segments. To take measure of the wing, semi-automatic software was developed by CIRAD-EMVT and IRD. It was used on wild populations of Glossina tachinoides Westwood and G. palpalis gambiensis trapped near Bobo-Dioulasso, Burkina Faso. From a digitized picture of the wing, the software calculates the length of vein segments, the ratios between these lengths, the surface of the tsetse characteristic "hatchet cell", and the greyness on the wings. The data were of taxonomic interest. In addition, they help to measure physiological characteristics of the fly populations studied.
12487
Hurd, H., 2003. Manipulation of medically important insect vectors by their parasites. [Glossina] Annual Review of Entomology, 48: 141-161.
Hurd: Centre for Applied Entomology and Parasitology, School of Life Sciences, Keele University, Keele, Staffordshire ST5 5BG, UK. [[email protected]]
Many of the most harmful parasitic diseases are transmitted by blood-feeding insect vectors. During this stage of their life cycles, selection pressures favour parasites that can manipulate their vectors to enhance transmission. Strategies may include increasing the amount of contact between vector and host, reducing vector reproductive output and consequently altering vector resource management to increase available nutrient reserves, and increasing vector longevity. Manipulation of these life-history traits may be more beneficial at some phase of the parasite's developmental process than at others. This review examines empirical, experimental and field-based evidence to evaluate examples of changes in vector behaviour and physiology that might be construed to be manipulative. Examples are mainly drawn from malaria-infected mosquitoes, Leishmania-infected sandflies, and Trypanosoma-infected tsetse flies.
12488
Kongoro, J.A., Osir, E.O., Imbuga, M.O. & Oguge, N.O., 2002. Comparison of midgut trypsin/lectin activities and trypanosome infection rates in three Glossina species. Insect Science and its Application, 22 (4): 295-301.
Kongoro: International Centre of Insect Physiology and Ecology (ICIPE), P. O. Box 30772, Nairobi 00506, Kenya.
Midgut trypsin and lectin levels were determined in three tsetse species, namely Glossina morsitans morsitans, G. longipennis and G. fuscipes fuscipes. In addition, the abilities of midgut homogenates prepared from these flies to transform bloodstream-form Trypanosoma brucei brucei and T. congolense were compared in vitro. In all the species examined, trypsin levels did not differ significantly up to 24 h post-bloodmeal. There were similar rates of transformation of the bloodstream-form trypanosomes into procyclic (midgut) forms in vivo, so that all species had similar levels of infection in the midgut. However, trypsin levels continued to increase beyond 24 h, reaching a peak between 48 and 72 h. The peak was lowest in G. morsitans morsitans. The midgut homogenates in this species also had the lowest levels of lectin. The species had the highest levels of mature T. congolense and T. brucei infections. We propose that the lower levels of peak midgut trypsin and lectin in G. morsitans morsitans are important in the establishment of trypanosome infections in this species of tsetse.
12489
Morales-Hojas, R., Post, R.J., Wilson, M.D. & Cheke, R.A., 2002. Completion of the sequence of the nuclear ribosomal DNA subunit of Simulium sanctipauli, with descriptions of the 18S, 28S genes and the IGS. [Glossina] Medical and Veterinary Entomology, 16 (4): 386-394.
Morales-Hojas and Cheke: Department of Entomology, The Natural History Museum, London, UK. [[email protected]; [email protected]]
We describe the IGS-ETS, 18S and 28S ribosomal gene sequences of Simulium sanctipauli, a member of the S. damnosum complex of blackflies (Diptera: Simuliidae). These regions, together with the ITS-1, ITS-2 and 5.8S rDNA presented elsewhere (accession number U36206), constitute the composite sequence of the entire rDNA unit, making S. sanctipauli the second dipteran species of medical importance for which the entire rDNA has been sequenced. Despite the lack of sequence identity, the IGS of S. sanctipauli showed some structural similarities to other Diptera, i.e. the mosquito Aedes albopictus (Culicidae), the fruitfly Drosophila melanogaster (Drosophilidae) and the tsetse Glossina (Glossinidae). Two blocks of tandemly repeated subunits were present in the IGS of S. sanctipauli and, unlike other species of Diptera, they contained no duplications of promoter-like sequences. However, two promoter-like sequences were identified in the unique DNA stretches of the IGS by their sequence similarity to the promoter of Aedes aegypti (Culicidae). The observed sequence variation can be explained, as in the case of Drosophila spp., by the occurrence of slippage-like and point mutation processes, with unequal crossing-over homogenizing (to a certain extent) the region throughout the gene family and blackfly population. The 18S and 28S rDNA genes show more intraspecific variability within the expansion segments than in the core regions. This is also the case in the interspecific comparison of these genes from S. sanctipauli with those of S. vittatum, Ae. albopictus and D. melanogaster. This pattern is typical of many eukaryotes and likely to be the result of a more relaxed functional selection in the expansion segments than on the core regions. The A+T content of the S. sanctipauli genes is high and similar to those of other Diptera. This could be the result of a change in the mutation pressure towards AT in the Diptera lineage.
12490
Shibata, C., Furukawa, A. & Mori, K., 2002. Syntheses of racemic and diastereomeric mixtures of 3,7,11,15-tetramethylhentriacontane and 4,8,12,16-tetramethyldotriacontane, the cuticular tetramethylalkanes of the tsetse fly, Glossina brevipalpis. Bioscience, Biotechnology and Biochemistry, 66 (3): 582-587.
Mori: Fuji Flavor Co. Inc, Insect Pheromone & Traps Division, Midorigaoka 3-5-8, Hamura, Tokyo 2058053, Japan.
Cuticular hydrocarbons of the tsetse fly, Glossina brevipalpis, contain 3,7,11,15-tetramethylhentriacontane and 4,8,12,16-tetramethyldotriacontane as possible candidates for its contact sex pheromone. These were synthesized as racemic and diastereomeric mixtures starting from racemic citronellol and employing phenylsulfone-mediated chain-elongation as the key reaction.
12491
Spath, J., 2002. Occurrence of the tsetse fly species Glossina longipalpis in peridomestic areas in the preforest zone of the Ivory Coast (Diptera: Glossinidae). Entomologia Generalis, 26 (3): 207-212 E.
Spath: Sossauer Str 49, D-84130 Dingolfing, Germany.
In West Africa, husbandry is extending into hitherto unused areas of the preforest zone. Thus, tsetse species (Glossina spp) occurring in these areas are now becoming economically and medically more important. The present paper reports on the occurrence of tsetse flies in peridomestic habitats surrounding a village in the preforest zone of Côte d'Ivoire. Catches consisted of 72 percent Glossina p. palpalis and 28 percent G. longipalpis. The first species is reported frequently to inhabit peridomestic areas, but this is the first detailed account of the occurrence of G. longipalpis in various village habitats. Glossina longipalpis was present in almost all habitats of the peridomestic study area. It reached its highest apparent density in and near the forest, whereas at those two sites of the study area which were most strongly modified by human activity - the centre of the village and the edge of a dirt road - no G. longipalpis were detected.
12492
Hargrove, J.W., 2003. Optimized simulation of the control of tsetse flies Glossina pallidipes and G. m. morsitans (Diptera: Glossinidae) using odour-baited targets in Zimbabwe. Bulletin of Entomological Research, 93 (1): 19-29.
Hargrove: 9 Monmouth Rd, Avondale, Harare, Zimbabwe. [john@zappuz. co.zw]
In 1984-1985 insecticide-treated targets were deployed in the 600 km2 Rifa Triangle, Zambezi Valley, Zimbabwe. Trap catches of Glossina pallidipes were modelled using a function combining logistic growth with diffusive movement. A simulation routine was linked to a non-linear least-squares optimization programme and fits optimized with respect to population carrying capacities, rates of growth and movement, and to levels of imposed mortality. In March-September 1984, the overall additional mortality was 2 percent per day of adult female G. pallidipes, increasing thereafter to 8 percent per day, due to the deployment of more targets, the onset of the hot, dry season and the ground-spraying of the adjoining Zambezi escarpment with DDT. For G. m. morsitans the corresponding estimates were 1 percent and 2 percent per day. For both species, the deployment of four targets km-2 in a closed population will ensure eradication. For G. m. morsitans a halving of target efficacy would reduce the killing rate to the point where eradication would be unlikely. Estimated daily displacements were c. 200 m for G. m. morsitans and 660 m for G. pallidipes. The lower rate for G. m. morsitans means that, while targets kill this species less effectively, re-invasion of cleared areas is slower. Targets do not markedly affect robust populations outside the deployment area. The Zambian tsetse population adjacent to the Rifa Triangle declined markedly during the experiment, however, suggesting that it is maintained largely by immigration. The methods developed here will be applied to data from other campaigns with the aim of improving the efficiency of tsetse control programmes.
12493
Mbongwe, B., Legrand, M., Blais, J.M., Kimpe, L.E., Ridal, J.J. & Lean, D.R.S., 2003. Dichlorodiphenyltrichloroethane in the aquatic ecosystem of the Okavango Delta, Botswana, South[ern] Africa. Environmental Toxicology and Chemistry, 22 (1): 7-19.
Lean: Department of Biology, University of Ottawa, 30 Marie Curie Road, Ottawa, Ontario K1N 6N5, Canada. [[email protected]]
Concentrations of DDT and its metabolites were measured in water, plants, invertebrates and fish from lagoons in the Okavango Delta, Botswana, where DDT has been used for approximately 50 years. The sampling area was sectioned to distinguish spraying for control of malaria and for control of African sleeping sickness. Average concentrations of total DDT (sum of DDT and its metabolites) ranged from 0.009 ng/litre in water to 18.76 ng/g wet weight in fish. These levels are approximately 1 percent of those found in piscivorous fish from temperate North America. The dichlorodiphenyl ethylene (DDE) metabolite was the most abundant fraction of total DDT. Although total DDT concentrations were higher in areas treated for malaria than areas treated for sleeping sickness, these concentrations were likely driven by factors other than the historic application of the pesticide. Equilibration with air concentrations was the most likely explanation for these levels. Since the mean annual temperature exceeded the temperature of vaporization of DDT, this research suggests the need for reliable transport models. Our results showed that total DDT concentration in fish was best explained by lipid content of the fish and trophic position inferred by ä15N, regardless of DDT application history in those areas. The reservoir above Gaborone Dam, an area downstream of the Okavango but where DDT had not been used, was sampled to compare total DDT levels to the treated areas. The two species (a herbivorous threespot tilapia and the omnivorous sharptooth catfish) from Gaborone had levels higher than those found in the Okavango Delta, but these differences can again be explained using trophic position inferred by ä15N rather than by fish size or location.
12494
Pearce, F., 2002. Fly screen - Taking the bite out of tsetse doesn't have to cost billions. [News item] New Scientist, 174 (2348): 17.
The article is mainly concerned with the merits of using fly netting around cattle, to reduce fly attack.
12495
Boulanger, N., Munks, R.J.L., Hamilton, J.V., Vovelle, F., Brun, R., Lehane, M.J. & Bulet, P., 2002. Epithelial innate immunity: a novel antimicrobial peptide with antiparasitic activity in the blood-sucking insect Stomoxys calcitrans. Journal of Biological Chemistry, 277 (51): 49921-49926.
Boulanger: Institut de Biologie Moléculaire et Cellulaire, 15 Rue René Descartes, 67084 Strasbourg Cedex, France. [[email protected]]
The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, taking Stomoxys calcitrans as a model. Stomoxys calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calcitrans is not a cyclical vector of trypanosomes, we have examined its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut of S. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity against Trypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes causing African sleeping sickness and nagana.
12496
Hutchinson, O.C., Fèvre, E.M., Carrington, M. & Welburn, S.C., 2003. Lessons learned from the emergence of a new Trypanosoma brucei rhodesiense sleeping sickness focus in Uganda. [Editorial comment] Lancet Infectious Diseases, 3 (1): 42-45.
Fèvre: Centre for Tropical Veterinary Medicine, Royal School of Veterinary Medicine, Royal School of Veterinary Studies, University of Edinburgh, EH25 9RG, UK. [[email protected]]
During the latter months of 1998, cases of sleeping sickness caused by Trypanosoma brucei rhodesiense presented in Soroti district, eastern Uganda, a region which had not previously experienced cases of the disease. Cattle are the main reservoir for T. b. rhodesiense, by contrast with sleeping sickness caused by T. b. gambiense in West Africa where there appears to be no epidemiologically significant animal reservoir. Several factors have been identified that interacted to produce ideal conditions for the establishment of a new disease focus. After a period of civil unrest, Soroti, which is within the tsetse belt, was repopulated by people and later, cattle. Both the cattle restocking and the subsequent trade in these cattle at a local cattle market had a role in the appearance of the disease. Recently, molecular biology techniques have become available for the detection and genotype identification of T. b. rhodesiense and thus it is now possible to distinguish human infective and non-infective trypanosomes in cattle. In light of these advances in identification and in both field and epidemiological techniques, successful disease control management has become an achievable goal and will require the collaboration and expertise of clinicians, veterinarians, epidemiologists and laboratory scientists.
12497
Wilson, R.T., 2003. Animal health and disease control in the Usangu Wetland of Southwestern Tanzania. Tropical Animal Health and Production, 35 (1): 47-67.
Wilson: Bartridge House, Umberleigh, North Devon, EX37 9AS, UK.
The Usangu Wetland in the Southern Highlands of Tanzania has always been a major livestock production area. This paper describes the physical and social environment of these Plains, before presenting a short history of the veterinary services in the area. The main part of the paper examines, through historical records and interviews with livestock owners and administrative officials, the history of the major diseases affecting livestock.
[See also 26: nos. 12512, 12513, 12516]
12498
Dje, N.N., Miezan, T.W., N'guessan, P., Brika, P., Doua, F. & Boa, F., 2003. Distribution géographique des trypanosomés pris en charge en Côte d'Ivoire de 1993 à 2000. [Geographic distribution of sleeping sickness patients treated in Côte d'Ivoire between 1993 and 2000]. Bulletin de la Société de Pathologie Exotique, 95 (5): 359-361 S P E.
Dje: Projet de recherches cliniques sur la trypanosomiase (PRCT), BP 1425 Daloa, Côte d'Ivoire.
HAT caused by Trypanosoma brucei gambiense is a chronic disease in Côte d'Ivoire. From 1993 to 2000, a total of 1616 patients were treated in the three therapy centres of the country, an average of 202 patients a year. The patients came from two main areas in the Centre West of the country in the Marahoue region: the districts of Sinfra, South of Bouaflé, and Bonon, West of Bouaflé. In the centre west and in the south east of the country (Aboisso-Ayame), patients are still affected by the disease, although these foci are less active. The remaining foci seem to be under control, although no active survey has been carried out. The areas where the greatest numbers of patients were recorded are the ones where cash crops (cocoa and coffee mainly) are grown and where rural activities tend to bring humans and tsetse flies in contact. This study provides figures for the number of patients treated and information on the endemic areas and areas at risk. It will help in the design of control strategies and assist decision makers determine where priority control programs should be implemented.
12499
Lejon, V. & Büscher, P., 2003. Le diagnostic du stade dans la maladie du sommeil: vers une nouvelle approche. [Diagnosis of the disease stage in sleeping sickness: towards a new approach]. Bulletin de la Société de Pathologie Exotique, 95 (5): 338-340.
Lejon: Institut de médecine tropicale, Département de parasitologie, Nationalestraat 155, B-2000 Antwerpen, Belgium. [[email protected]]
Diagnosis of the neurological disease stage in Trypanosoma brucei gambiense infection is essential to select an optimal chemotherapy. The actual parameters for stage determination, the cerebrospinal fluid (CSF) cell count, total protein concentration and trypanosome detection, are insufficiently specific and sensitive. In order to identify new parameters for stage determination, we studied the neuro-inflammatory immune response in the central nervous system, notably the intrathecal humoral immune response in sleeping sickness patients. The presence of intrathecal IgM synthesis was identified as an excellent marker of central nervous system involvement. However, intrathecal IgM detection cannot be performed under field conditions. As a consequence of the strong intrathecal IgM synthesis, extremely high concentrations of IgM are found in the CSF of sleeping sickness patients. We therefore developed a latex agglutination field test (LATEX/IgM) indicative for intrathecal IgM synthesis and CNS involvement in sleeping sickness. Based on our observations on the intrathecal immune response and with LATEX/IgM, we propose a new approach for stage determination in sleeping sickness.
12500
Louis, F.J., Simarro, P.P. & Lucas, P., 2003. Maladie du sommeil: cent ans d'évolution des stratégies de lutte. [Sleeping sickness: a century of evolution of control strategies]. Bulletin de la Société de Pathologie Exotique, 95 (5): 331-336 S P E.
Louis: Cellule inter-régionale de surveillance et de lutte contre la trypanosomiase humaine africaine, OMS CDS/CSR, BP 155, Yaoundé, Cameroon. [[email protected]]
Sleeping sickness has been known since the fifteenth century but real progress in our knowledge of the disease occurred in the nineteenth century with the development of microscopy. From 1841 to 1901 the parasites and their vectors were identified, and the symptomatology and epidemiology were described. However, due to absence of any effective cure, the campaign against the disease was still based on the isolation of the patients and the transfer of exposed populations. The discovery of atoxyl in 1905 provided doctors with their first therapeutic weapon and, in 1910, the first action of vector control was undertaken with success in the Island of Principe. Between the two world wars, Jamot published guidelines for fighting against major outbreaks. Their application in Oubangui-Chari, in Cameroon and in French West Africa brought tremendous results and saw the triumph of the mobile unit concept. By the sixties one could believe that the disease had been eradicated. From the sixties to the nineties, the concept of the integration of screening and treatment, as well as the exclusion of any vertical control system, led gradually to new outbreaks of sleeping sickness in the known foci. Paradoxically, this was a time rich in discovery as regards diagnosis, treatment and entomology. In 1994, the World Health Organization became concerned with the situation of the disease in Central Africa where the major outbreaks of the disease occurred. A second paradox appeared: the nearly complete lack of interest shown by politicians and donors would be its salvation. Sleeping sickness has now become a typical example of an orphan disease. In 2001, an agreement between the WHO and the pharmaceutical industry brought back the funding required to fight the disease. Basically, it is a matter of resuming the action by using what still exists and by creating new strategies taking account of the extreme lack of human and logistical resources. The objective is to eradicate the sleeping sickness as a public health problem. The challenge is huge, but is on the way to success.
12501
Oscherwitz, S.L., 2003. East African trypanosomiasis. Journal of Travel Medicine, 10 (2): 141-143.
Oscherwitz: 2501 E. Southern Avenue, 22, Tempe, Arizona. AZ85282, USA.
The clinical history is described of a 56-year-old male tourist suspected to be infected with T. b. rhodesiense, and the successful subsequent treatment. Guidelines to differential diagnosis are suggested for clinicians faced with febrile patients who have recently returned from Africa. A short review of recent cases of tourists returning to USA with human African trypanosomiasis is given.
12502
Penchenier, L., Grébaut, P., Njokou, F., Eyenga, V.E. & Büscher, P., 2003. Evaluation of LATEX/T.b.gambiense for mass screening of Trypanosoma brucei gambiense sleeping sickness in Central Africa. Acta Tropica, 85(1): 31-37.
Penchenier: OCEAC, PO Box 288, Yaoundé, Cameroon; ORSTOM, 911 Avenue Agropolis, F-34000 Montpellier 01, France.
We compared the Card Agglutination Test for Trypanosomiasis (CATT), which consists of lyophilized bloodstream-form trypomastigotes of Trypanosoma brucei gambiense (T. b. g.) variable antigen type LiTat 1.3, with LATEX/T. b. g., which consists of a lyophilized suspension of latex particles coated with variable surface glycoproteins of T. b. g. variable antigen types LiTat 1.3, 1.5 and 1.6. This study was carried out during two mass screening surveys in 1998 in Campo, a sleeping sickness focus in Cameroon, with a low prevalence (0.3 percent) and in 1999 in Batangafo, which belongs to the Central African focus of Ouham, which has a higher prevalence (3 percent). In Campo, we compared the CATT performed on whole blood with the LATEX/T. b. g. on diluted blood. In Batangafo, both tests were performed on diluted blood. In all circumstances, the specificity of the LATEX/T. b. g. was higher than of CATT. The use of LATEX/T. b. g. on diluted blood instead of CATT results in an important decrease of workload and, as a consequence, of costs related to parasitological examinations. In the case of Campo the workload was up to twelve times less than when using CATT 1.3 on whole blood and the cost reduced to a third. In Batangafo the workload was decreased by nearly 20 percent with the LATEX/T. b. g. Finally, it should be noted that in Batangafo, one of the parasitologically confirmed sleeping sickness patients was negative in CATT and positive in LATEX/T. b. g., and that the reading of the test result in LATEX/T. b. g. is easier than in CATT.
12503
Pépin, J., Mpia, B. & Iloasebe, M., 2002. Trypanosoma brucei gambiense African trypanosomiasis: differences between men and women in severity of disease and response to treatment. Transactions of the Royal Society of Tropical Medicine and Hygiene, 96 (4): 421-426.
Pépin: Centre for International Health, 3001, 12ème Avenue Nord, Sherbrooke, Quebec, J1H 5N4 Canada. [[email protected]]
To compare the characteristics of women and men with Trypanosoma brucei gambiense trypanosomiasis, all 3231 cases treated in Nioki hospital, Democratic Republic of Congo, from 1982 to 2000 were reviewed for demographic information, date and mode of diagnosis, pre-treatment cerebrospinal fluid (CSF) examination, treatment given and its adverse effects, and whether a diagnosis of relapse was made during post-treatment follow-up. Women had a higher apparent incidence of Gambian trypanosomiasis than men (1768 cases in females, 1463 in males), due to selective migration of males out of endemic foci and potentially to a higher exposure among females. Women presented with a less-advanced disease than men: 27 percent (384/1431) of women had CSF trypanosomes and 72 percent (1024/1431) had an abnormal CSF white cell count, while corresponding figures in men were 39 percent (431/1115) and 82 percent (910/1115) (P < 0.001 for both comparisons), presumably because of differences in health-seeking behaviour. Men (61/718, 8.5 percent) were more likely to relapse after melarsoprol treatment than women (41/857, 4.8 percent) (P = 0.004), even after adjustment for other independent risk factors in multivariate analysis. The cause of this higher risk of treatment failure among men treated with melarsoprol remains unclear.
12504
Schwartz, M.D., 2003. Fever in the returning traveler, Part one: A methodological approach to initial evaluation. Wilderness and Environmental Medicine, 14 (1): 24-32.
Schwartz: Department of Emergency Medicine, Emory University/Centers for Disease Control, 1600 Clifton Avenue, MS E-28, Atlanta, GA 30333, USA. [[email protected]]
The advent of modern commercial air travel ensures that a returning traveller could present to any emergency department or private physician's office in the United States bearing any infection from the farthest corner of the earth. Exotic illnesses in the returned traveller are of concern to the physician because they often strike an otherwise young and healthy segment of the population and may carry significant morbidity and mortality if not recognized early. The infrequency with which these diseases are encountered demands a systematic approach to history, a physical examination, and the construction of a differential diagnosis. Information about the geographic distribution, routes of transmission, and incubation periods of the pathogens allows a clinician to reduce the differential to a manageable number of the likeliest aetiologies. This article proposes an algorithm for use by the physician faced with a febrile returned traveller. The clinical features of specific diseases and their incubation periods are presented to support the assumptions on which an algorithm-centred approach is based.
[See also 26: nos 12518, 12568]
12505
Buguet, A., Bourdon, L., Bisser, S., Chapotot, E., Radomski, M.W. & Dumas, M., 2003. La maladie du sommeil: trouble majeur des rythmes circadiens. [Sleeping sickness: a major disorder of circadian rhythm]. Bulletin de la Société de Pathologie Exotique, 95 (5): 337 S P E.
Buguet: Institut de médecine tropicale du service de santé des armées, Le Pharo, BP 46, 13998 Marseille Armées, France. [[email protected]]
At the meningoencephalitis stage, human African trypanosomiasis (HAT), sleeping sickness, causes dysregulation of the circadian rhythm of the sleep/wake cycle, rather than hypersomnia. In bedridden patients, total sleep time does not exceed nine hours. The change in the 24-hour distribution of sleep and wakefulness is proportional to the severity of clinical symptoms and laboratory abnormalities. The internal structure of sleep is also altered. All patients present sleep onset rapid eye movement periods (SOREMP), i.e., several sleep episodes beginning with rapid eye movement (REM) sleep. In mild cases, treatment with melarsoprol reverses circadian dysregulation, and SOREMP either decrease in number or disappear. Other circadian disturbances may be observed in HAT. These may include circadian dysrhythmia of hormonal secretions, but the relationship between hormonal pulses and sleep/wake states is preserved. The circadian rhythm of secretion of prolactin, renin, growth hormone and cortisol disappears in severe cases, but persists in mild ones. The amplitude and mean 24-hour value of plasma melatonin are normal with nocturnal peaks and no diurnal secretion. However, peak melatonin secretion occurs two hours earlier than in healthy African controls. In conclusion, HAT-induced dysregulation of circadian rhythm is proportional to disease severity. Presence of SOREMP and precocity of peak melatonin secretion support disturbance of the serotoninergic network rather than direct action on the biological clock.
12506
Donelson, J.E., 2003. Antigenic variation and the African trypanosome genome. Acta Tropica, 85 (3): 391-404.
Donelson: Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA. [[email protected]]
African trypanosomes are protozoan parasites that reside in the mammalian bloodstream where they constantly confront the immune responses directed against them. They keep one step ahead of the immune system by continually switching from the expression of one variant surface glycoprotein (VSG) on their surface to the expression of another immunologically distinct VSG - a phenomenon called antigenic variation. About 1000 VSG genes (VSGs) and pseudo-VSGs are scattered throughout the trypanosome genome, all of which are transcriptionally silent except for one. Usually, the active VSG has been recently duplicated and translocated to one of about 20 potential bloodstream VSG expression sites (B-ESs). Each of the 20 potential B-ESs is adjacent to a chromosomal telomere, but only one B-ES is actively transcribed in a given organism. Recent evidence suggests the active B-ES is situated in an extra-nucleolar body of the nucleus where it is transcribed by RNA polymerase I. Members of another group of about 20 telomere-linked VSG expression sites (the M-ESs) are expressed only during the metacyclic stage of the parasite in its tsetse fly vector. Progress in sequencing the African trypanosome genome has led to additional insights on the organization of genes within both groups of ESs that may ultimately suggest better ways to control or eliminate this deadly pathogen.
12507
Lundkvist, G.B., Hill, R.H. & Kristensson, K., 2002. Disruption of circadian rhythms in synaptic activity of the suprachiasmatic nuclei by African trypanosomes and cytokines. [Rats] Neurobiology of Disease, 11 (1): 20-27.
Kristensson: Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden. [[email protected]]
Disturbances in biological rhythms pose a major disease problem, not the least in the aging population. Experimental sleeping sickness, caused by Trypanosoma brucei brucei, in rats constitutes a unique and robust chronic model for studying mechanisms of such disturbances. The spontaneous postsynaptic activity was recorded in slice preparations of the suprachiasmatic nuclei (SCN), which contain the master pacemaker for circadian rhythms in mammals, from trypanosome-infected rats. The excitatory synaptic events, which in normal rats show a daily variation, were reduced in frequency, while the inhibitory synaptic events did not significantly differ. This indicates selective disturbances in glutamate receptor-mediated neurotransmission in the SCN. Treatment with interferon-ã in combination with lipopolysaccharide, which has synergistic actions with cytokines, and tumour necrosis factor-á similarly caused a reduction in excitatory synaptic SCN activity. We suggest that changes in the synaptic machinery of SCN neurons play an important pathogenetic role in sleeping sickness, and that proinflammatory cytokines can mimic these changes.
12508
Stephenson, J., 2003. Sleeping sickness strategy. Journal of the American Medical Association, 289 (14): 1774. (News Item)
This short item summarizes the work of Vanhamme et al., 2003 (Nature 222:83-87; see TTIQ 26 (1): 12573). Some strains of T. b. rhodesiense overcome the trypanosome lytic factor in human serum by making a serum resistance-associated protein (SRA) variant. The work reported on identifies the trypanosome lytic factor as apolipoprotein L-1 (apoL-1), and suggests that SRA binds to and disables apoL-1.
12509
Dumas, M. & Bouteille, B., 2003. La trypanosomose humaine africaine: propos sur le traitement actuel et les perspectives. [Human african trypanosomiasis, present treatment and future prospects]. Bulletin de la Société de Pathologie Exotique, 95 (5): 341-344 S P E.
Dumas: Institut d'épidémiologie neurologique et de neurologie tropicale, 2 rue du Docteur Marcland, 87025 Limoge cedex, France. [[email protected]]
General Lapeyssonnie's feelings oscillated between passion, disappointment, rebellion and hope when faced with the uncertainties of the therapy for HAT. A lack of political and financial concern during the past decades prevented the emergence of a genuine global policy to fight the disease and of research to develop new treatments against HAT. Today, some changes appear to be taking place. They are the result of the alarming spread of the disease and of the moral obligation that forces pharmaceutical companies to intervene. Drug research needs to be increased. The focus of research for new treatments is known: the new drugs should not be toxic and should be able to cross through the blood-brain barrier and reach high concentrations in the cerebrospinal fluid. They should be easy to synthesize, easy to use and the cost should be low. In 2002, megazol is the only product in preclinical development that seems to meet each of these criteria.
[See also 26: no. 12496]
12510
Ahmadu, B., Lovelace, C.E.A. & Samui, K.L., 2002. A survey of trypanosomosis in Zambian goats using haematocrit centrifuge technique and polymerase chain reaction. Journal of the South African Veterinary Association, 73 (4): 224-226.
Ahmadu: Department of Disease Control, School of Veterinary Medicine, University of Zambia, PO Box 32379, Lusaka, Zambia. Present address: Department of Animal Health and Production, Veterinary Field Station, PO Box 17, Jwaneng, Botswana. [[email protected]]
The incidence of trypanosomosis was determined using the haematocrit centrifuge technique as well as polymerase chain reaction on 120 goat blood spots on filter paper. Both techniques failed to detect a positive reaction, implying that (small sample size notwithstanding) trypanosomosis does not seem to pose a serious threat to goat health in the districts from where the animals originated.
12511
Geysen, D., Delespaux, V. & Geerts, S., 2003. PCR-RFLP using Ssu-rDNA amplification as an easy method for species-specific diagnosis of Trypanosoma species in cattle. Veterinary Parasitology, 110 (3-4): 171-180.
Geysen: Institute of Tropical Medicine, Nationaalestraat 155, B-2000 Antwerp, Belgium. [[email protected]]
A single polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay was used to characterize all important bovine trypanosome species. This is the first report of a sensitive pan-trypanosome PCR assay amplifying all species including T. vivax to a comparable extent using a single primer pair. A semi-nested PCR approach resulted in the detection of one T. congolense trypanosome genome/40 ìl of blood, applied as buffy coat on filter paper. Restriction enzyme analysis using Mspl and Eco571 gave a clear distinction between T. congolense, T. brucei, T. vivax and T. theileri. Several subgroups within the T. congolense group could be distinguished but no differences between the species belonging to the subgenus Trypanozoon or between T. simiae and T. theileri could be found. The use of MboII restriction enzyme allowed differentiation between T. simiae and T. theileri. The potential of the essay to be used as a suitable diagnostic tool is discussed.
12512
Herder, S., Simo, G., Nkinin, S. & Njiokou, F., 2002. Identification of trypanosomes in wild animals from Southern Cameroon using the polymerase chain reaction (PCR). Parasite, 9 (4): 345-349.
Herder: LRCT IRD/CIRAD, Campus international de Baillarguet, F-34398 Montpellier Cedex 5, France.
One possible explanation of the maintenance of many historical foci of sleeping sickness in Central Africa could be the existence of a wild animal reservoir. In this study, PCR was used to detect the different trypanosome species present in wild animals captured by hunters in the southern forest belt of Cameroon (Bipindi). Trypanosomes were also detected by a parasitological method (quantitative buffy coat: QBC). Parasite could not be isolated in culture medium (kit for in vitro isolation: KIVI). Specific primers of T. brucei s.l., T. congolense forest type, T. congolense savannah type, T. vivax, T. simiae and T. gambiense group 1 were used to identify parasites in the blood of 164 animals belonging to 24 different species including ungulates, rodents, pangolins, carnivores, reptiles and primates. Blood samples were collected during the rainy season in July and in October 1999. Of the 24 studied species, eight were carrying T. gambiense group 1. Those parasites pathogenic to man were found in monkeys (Cercocebus torquatus and Cercopithecus nictitans), in ungulates (Cephalophus dorsalis and C. monticola), in carnivores (Nandinia binotata and Genetta servalina) and in rodents (Cricetomys gambianus and Atherurus africanus). 13 species (54 percent) were carrying T. brucei s.l. identified as non-gambiense group 1.
12513
Jeneby, M.M., Suleman, M.A. & Gichuki, C., 2002. Sero-epizootiologic survey of Trypanosoma brucei in Kenyan nonhuman primates. Journal of Zoo and Wildlife Medicine, 33(4): 337-341.
Suleman: Division of Ecology, Conservation and Diseases, Institute of Primate Research, PO Box 24481, Karen, Nairobi, Kenya.
Blood samples were collected from 121 individuals of three species of wild-caught nonhuman primates from Kenya, including African green monkeys (Cercopithecus aethiops), Syke's monkeys (C. mitis), and olive baboons (Papio cynocephalus anubis), and were examined for circulating Trypanosoma brucei and for T. brucei antigen and anti-trypanosome antibody. Indirect antibody enzyme-linked immunosorbent assay detected titers of anti-T. brucei antibodies in 13 of the primates sampled, and field-oriented latex agglutination test detected invariant T. brucei antigens in ten (8.3 percent) of the primates. However, no trypanosomes were visible in blood smears, on wet blood films, or by buffy coat technique, nor were they demonstrable in a subset of C. aethiops individuals that were studied using mouse subinoculation.
[See also 26: no. 12520]
12514
Mohamed, H.E. & Beynen, A.C., 2002. Ascorbic acid content of blood plasma, erythrocytes, leukocytes and liver in camels (Camelus dromedarius) without or with parasite infections. International Journal for Vitamin and Nutrition Research, 72 (6): 369-371.
Mohamed: Department of Biochemistry, Faculty of Veterinary Science Shambat, University of Khartoum, Khartoum North, Sudan.
Healthy camels (Camelus dromedarius) and those naturally infected with trypanosomiasis, sarcoptic mange and helminthiasis were compared as to ascorbic acid (vitamin C) contents of red blood cells, white blood cells, whole blood, plasma, and liver. The camels were kept under natural grazing conditions in Sudan. Reduced levels of vitamin C were found in camels with parasite infections, especially in animals with trypanosomiasis. It is suggested that the low vitamin C status in infected camels is caused by increased utilization and/or decreased synthesis of vitamin C.
12515
Naessens, J., Leak, S.G.A., Kennedy, D.J., Kemp, S.J. & Teale, A.J., 2003. Responses of bovine chimaeras combining trypanosomosis resistant and susceptible genotypes to experimental infection with Trypanosoma congolense. Veterinary Parasitology, 111 (2-3): 125-142.
Naessens: ILRI, Box 30709, Nairobi, Kenya.
West African N'Dama cattle have developed a genetic capacity to survive, reproduce and remain productive under trypanosomosis risk. The cellular and molecular bases of this so-called trypanotolerance are not known, but the trait is manifested by the N'Dama's greater capacity to control parasitaemia and anaemia development during an infection. In order to examine the role of the haematopoietic system in trypanotolerance, we have exploited the tendency for the placentas of bovine twin embryos to fuse. Placental fusion in cattle results in bone marrow chimaerism in twins. By comparison with the N'Dama, cattle of the East African Boran breed are relatively susceptible. We evaluated the role of the haemopoietic system in trypanotolerance by comparing the performance of five Chimaeric Boran/N'Dama twin calves with that of singletons of the two breeds. Chimaeric Boran/N'Dama pairs of twins were produced in recipient Boran cows by embryo transfer, and the majority of haemopoietic cells in all twinned individuals were of Boran origin. Thus, N'Dama chimaeras differed from N'Dama singletons in that the bulk of their haemopoietic system was derived from their susceptible Boran twins, while Boran chimaeras differed little from Boran control animals. All cattle became parasitaemic and developed anaemia. The N'Dama chimaeras did not manage their anaemia and white blood cell counts effectively. However, they were able to limit parasitaemia development. These results suggest that trypanotolerance is the result of two mechanisms, one that improves parasite control and is independent of the genetic origin of the haemopoietic tissue, and another that is influenced by haemopoietic tissue genotype and which improves control over anaemia. The capacity to maintain growth during infection was similarly dependent on the genetic origin of the haemopoietic tissue.
12516
Radwanska, M., Chamekh, M., Vanhamme, L., Claes, F., Magez, S., Magnus, E., De Baetselier, P., Büscher, P. & Pays, E., 2002. The serum resistance-associated gene as a diagnostic tool for the detection of Trypanosoma brucei rhodesiense. American Journal of Tropical Medicine and Hygiene, 67 (6): 684-690.
Radwanska: Department of Immunology, Grote Schuur Hospital, Old Main Building H47, Observaory 7925, Cape Town, South Africa. [[email protected]]
In the search for new diagnostic methods that would distinguish Trypanosoma brucei rhodesiense from T. b. brucei and T. b. gambiense, we have developed two polymerase chain reaction (PCR) primer sets. The first primer set was derived from the serum resistance-associated (SRA) gene of T. b. rhodesiense that confers resistance to lysis by normal human serum (NHS). The specificity of the SRA-based PCR was tested on 97 different trypanosome populations originating from various taxonomic groups, host species, and geographic regions. Only one of 25 T. b. rhodesiense samples was negative in this PCR and none of 72 other samples were positive in this assay. Interestingly, a reference T. brucei strain (TREU927/4) currently used for genome sequencing was negative for the SRA gene; however, this strain was resistant to lysis by NHS. The second primer set was derived from a specific variant surface glycoprotein (VSG) expression site where the SRA gene is expressed (R-ES). This primer set identified the strain as T. b. rhodesiense in 17 of 17 SRA gene-positive strains in which it was tested. These data strongly suggest that expression of the SRA gene is generally involved in resistance to lysis by NHS in T. b. rhodesiense strains.
12517
Agu, W. E. & Egbuji, A. N., 2002. Urine albumin level in mice infected with Trypanosoma brucei. Veterinarski Arhiv, 72 (2): 101-108.
Agu: Department of Veterinary Parasitology and Entomology, University of Nigeria, Nsukka, Nigeria.
Urine albumin levels were evaluated in mice infected with Trypanosoma brucei using urine strips. The urine albumin level in some of the infected mice began to increase on the sixth day post-infection, and by the twelfth day, all infected mice showed a high level of albumin in urine which progressively increased with time. There was a high level of significance with mean urine albumin levels being significantly higher in trypanosome-infected mice than non-infected control mice. As infection progressed, there was also a significant increase with mean urine albumin levels increasing with time. It is concluded that urine albumin can be used to indicate trypanosomosis.
12518
Chiejina, S.N., Wakelin, D. & Goyal, P.K., 2003. Trypanosome-induced modulation of responses to concurrent helminth infection. [mice] Research in Veterinary Science, 74 (1): 47-53.
Wakelin: School of Life and Environmental Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK. [[email protected]]
Infections with African trypanosomes are known to suppress immune responses to vaccines and to gastrointestinal nematode infections in livestock. Experimental infections with Trypanosoma brucei and the gastrointestinal nematode Nippostrongylus brasiliensis in mice were used to identify possible mechanisms involved in interference with anti-worm responses and to examine the effects of host genotype on the extent of suppression seen. Concurrent infections with T. brucei resulted in a prolongation of worm survival and a dramatic increase in faecal egg output. Infection also resulted in a marked suppression of the proliferative response of mesenteric lymphocytes (MLNC) to in vitro mitogenic stimulation. When MLNC from concurrently infected mice were stimulated in vitro with the mitogen ConA they released more IFN-ã and less IL-5 than cells from mice infected only with N. brasiliensis. These data are interpreted in terms of a trypanosome-mediated influence on the development of host-protective type-2 T helper cell responses against N. brasiliensis. The degree to which T. brucei altered the kinetics of the nematode infection was influenced by the particular mouse strain used.
12519
Chauvière, G., Bouteille, B., Enanga, B., de Albuquerque, C., Croft, S.L., Dumas, M. & Périe, J., 2003. Synthesis and biological activity of nitro heterocycles analogous to megazol, a trypanocidal lead. [Primates] Journal of Medicinal Chemistry, 46 (3): 427-440.
Chauvière: Groupe de Chimie Organique Biologique, Laboratoire de Synthèse et Physicochemie de Molécules d'Interêt Biologique, Université Paul Sabatier, UMR CNRS 5068, 31062 Toulouse, France. [[email protected]]
As part of our efforts to develop new compounds aimed at the therapy of parasitic infections, we synthesized and assayed analogues of a lead compound megazol, 5-(1-methyl-5-nitro-IH2-imidazolyl)-1,3,4-thiadiazol-2-amine, CAS no. 19622-55-0), in vitro. We first developed a new route for the synthesis of megazol. Subsequently several structural changes were introduced. Assays of the series of compounds on the protozoan parasites Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donouani, as either extracellular cells or infected macrophages, indicated that megazol was more active than the derivatives. Megazol was then evaluated on primates infected with Trypanosoma brucei gambiense, including late-stage central nervous system infections in combination with suramin. Full recovery was observed in five monkeys in the study with no relapse of parasitemia within a two-year follow-up. Because there is a lack of efficacious treatments for sleeping sickness in Africa and Chagas disease in South America, megazol is proposed as a potential alternative. The mutagenicity of this compound is at present being re-evaluated, and metabolism is also under investigation prior to possible further developments.
12520
Egbe-Nwiyi, T.N., Igbokwe, I.O. & Onyeyili, P.A., 2003. The pathogenicity of diminazene aceturate-resistant Trypanosoma brucei in rats after treatment with the drug. Journal of Comparative Pathology, 128 (2-3): 188-191.
Egbe-Nwiyi: Department of Veterinary Pathology, University of Maiduguri, P.M.B. 1069, Maiduguri, Borno State, Nigeria.
Four groups (A, B, C and D) of ten rats were used to determine the effect of comparatively high doses of diminazene aceturate on diminazene aceturate-resistant Trypanosoma brucei and the pathogenic effect of relapse infection. Group A rats were uninfected (controls) while group B, C and D rats were inoculated intraperitoneally with 0.5 × 106 diminazene aceturate-resistant T. brucei and treated with diminazene aceturate at 14.0, 17.5 and 21.0 mg/kg body weight, respectively, on day 14 post-infection (PI) as a single intraperitoneal injection. Prepatent periods and also levels of parasitaemia were comparable in groups B, C and D. Packed cell volume (PCV) decreased in the infected groups by day 14 PI and returned to pre-infection values by day 63 post-treatment (PT). Anaemia was comparable in groups B, C and D. Relapse parasitaemia occurred in six rats in group B on day 70 PT and in five rats in each of groups C and D on day 77 PT. The PCV of the rats with relapse infection decreased progressively up to day 105 PT, when the experiment was terminated, whereas the PCV of rats without relapse did not. The levels of anaemia and parasitaemia on day 14 post-relapse were significantly higher (P < 0.05) than the levels obtained on day 14 PI in the same animals. Thus, comparatively high doses of diminazene aceturate failed to cure drug-resistant T. brucei infection in 50-60 percent of infected rats and relapse infections were more severe than the primary infections before treatment.
12521
Kaiser, A., Gottwald, A., Wiersch, C., Maier, W. & Seitz, H. M., 2002. The necessity to develop drugs against parasitic diseases. [Review] Pharmazie, 57 (11): 723-728.
Kaiser: Institut für Medizinische Parasitologie, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany. [[email protected]]
This review focuses on the most significant trends in the development of drugs for the treatment of malaria, African sleeping sickness and toxoplasmosis. In the case of malaria, the trends include new fixed-dose artemisinin combinations, antifolates and new targets in the apicoplast of Plasmodium falciparum. Targets in the treatment of trypanosomiasis are the biosynthesis of glycosylphosphatidylinositol and enzymes involved in the biosynthesis of trypanothione. Efforts to develop a vaccine against toxoplasmosis are also discussed.
12522
Kamnaing, P., Tsopmo, A., Tanifum, E.A., Tchuendem, M.H.K., Tane, P., Ayafor, J.F., Sterner, O., Rattendi, D., Iwu, M.M., Schuster, B. & Bacchi, C., 2003. Trypanocidal diarylheptanoids from Aframomum letestuianum. Journal of Natural Products, 66 (3): 364-367.
Sterner: Department of Organic and Bioorganic Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden. [Olov.Sterner @bioorganic.lth.se]
12523
Wang, J., Van Praagh, A., Hamilton, E., Wang, Q., Zou, B.X., Muranjan, M., Murphy, N.B. & Black, S.J., 2002. Serum xanthine oxidase: Origin, regulation, and contribution to control of trypanosome parasitemia. Antioxidants and Redox Signalling, 4 (1): 161-178.
Black: Department of Veterinary and Animal Science, University of Massachusetts, Amhurst, MA 01003, USA.
African trypanosomiasis is caused by Salivarian trypanosomes, tsetse fly-transmitted protozoa that inhabit the blood plasma, lymph and interstitial fluids, and, in the case of Trypanosoma brucei species, also the cerebrospinal fluid of mammal hosts. Trypanosomiasis in people and domestic animals manifests as recurring waves of parasites in the blood and is typically fatal. In contrast, trypanosomiasis in Cape buffaloes, which are naturally selected to resist the disease, is characterized by the development of only one or a few waves of parasitaemia, after which the infection becomes cryptic, being maintained by the presence of 1-20 mammal-infective organisms/ml of blood. The control of the acute phase of parasitaemia in Cape buffaloes correlates with a decline in blood catalase activity and the generation of trypanocidal H2O2 in serum during the catabolism of endogenous purine by xanthine oxidase. Here we review features of this response, and of trypanosome metabolism, that facilitate H2O2-mediated killing of the parasites with minimal damage to the host. We also discuss the origin and regulation of serum xanthine oxidase and catalase, and show how recovery of serum catalase in infected Cape buffaloes precludes a role for H2O2 in the long-term, stable suppression of trypanosome parasitaemia.
12524
Breidbach, T., Ngazoa, E. & Steverding, D., 2002. Trypanosoma brucei: in vitro slender-to-stumpy differentiation of culture-adapted, monomorphic bloodstream forms. Experimental Parasitology, 101 (4): 223-230.
Steverding: Abteilung Parasitologie, Hygiene-Institut der Ruprecht-Karls Universität, Im Neuerheimer Feld 324, D-69120 Heidelberg, Germany. [[email protected]]
[See also 26: no. 12524]
12525
Simpson, A.G.B., Lukeš, J. & Roger, A.J., 2002. The evolutionary history of kinetoplastids and their kinetoplasts. [T. brucei] Molecular Biology and Evolution, 19 (12): 2071-2083.
Simpson: Department of Biochemistry, Canadian Institute for Advanced Research, Program in Evolutionary Biology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7 Canada. [[email protected]]
12526
Turner, C.M.R., 2002. A perspective on clonal phenotypic (antigenic) variation in protozoan parasites. Parasitology, 125 (Suppl.): S17-S23.
Turner: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK. [[email protected]]
Intra-clonal phenotypic (antigenic) variation is used by many pathogens to evade the consequences of immune-mediated killing by mammalian hosts. In this substantially theoretical article, it is emphasized that antigenic variation (sensu stricto) involves no change in genotype; it is important as a mechanism for promoting pathogen transmission and it has a polyphyletic origin. From a functional perspective, antigenic variation is constrained by the requirement to meet five conditions. These are: capability to express several antigens against which functional immunity predominates; capability to interact with the environment; mutually exclusive expression of variable antigens in each cell within an infection; mutually exclusive expression in the within-host pathogen population and the capability for population growth within a host. Meeting these conditions leads to chronicity of infection and high rates of hierarchical and reversible switching of expression between variable antigens. The organization of hierarchical expression is discussed in some detail.
[See also 26: 12506, 12516, 12524]
12527
Alsford, N.S., Navarro, M., Jamnadass, H.R., Dunbar, H., Ackroyd, M., Murphy, N.B., Gull, K. & Ersfeld, K., 2003. The identification of circular extrachromosomal DNA in the nuclear genome of Trypanosoma brucei. Molecular Microbiology, 47 (2): 277-289.
Ersfeld: School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK. [[email protected]]
12528
Aphasizhev, R., Sbicego, S., Peris, M., Jang, S.H., Aphasizheva, I., Simpson, A.M., Rivlin, A. & Simpson, L., 2002. Trypanosome mitochondrial 3? terminal uridylyl transferase (TUTase): The key enzyme in U-insertion/deletion RNA editing (vol. 108, pg 637, 2002) (Correction: see TTIQ, 25(1): 12171). Cell, 110 (1): 133.
Simpson: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California 90095, USA. [[email protected]]
12529
Bütikofer, P., Jelk, J., Malherbe, T., Vassella, E., Acosta-Serrano, A., Renggli, C.K., Brun, R. & Roditi, I., 2003. Phosphorylation of GPEET procyclin is not necessary for survival of Trypanosoma brucei procyclic forms in culture and in the tsetse fly midgut. Molecular and Biochemical Parasitology, 126 (2): 287-291.
Bütikofer: Institute of Biochemistry and Molecular Biology, University of Bern, 3012 Bern, Switzerland. [[email protected]]
12530
Camacho, M. del R., Phillipson, J. D., Croft, S. L., Marley, D., Kirby, G. C. & Warhurst, D. C., 2002. Assessment of the antiprotozoal activity of Galphimia glauca and the isolation of new nor-secofriedelanes and nor-friedelanes. Journal of Natural Products, 65 (10): 1457-1461
Camacho: Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
12531
Campillo, N. & Carrington, M., 2003. The origin of the serum resistance associated (SRA) gene and a model of the structure of the SRA polypeptide from Trypanosoma brucei rhodesiense. Molecular and Biochemical Parasitology, 127 (1): 79-84.
Carrington: Department of Biochemistry, 80 Tennis Court Road, Cambridge CB2 1GA, UK. [[email protected]]
12532
Chang, T.H., Milne, K.G., Güther, M.L.S., Smith, T.K. & Ferguson, M.A.J., 2002. Cloning of Trypanosoma brucei and Leishmania major genes encoding the GlcNAc-phosphatidylinositol De-N-acetylase of glycosylphosphatidyl-inositol biosynthesis that is essential to the African Sleeping sickness parasite. Journal of Biological Chemistry, 277 (51): 50176-50182.
Ferguson: Division of Biological Chemistry and Molecular Microbiology, The Wellcome Trust Biocentre, The School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. [[email protected]]
12533
Chen, Y.L., Hung, C.-H., Burderer, T. & Lee, G.-S.M., 2003. Development of RNA interference revertants in Trypanosoma brucei cell lines generated with a double stranded RNA expression construct driven by two opposing promoters. Molecular and Biochemical Parasitology, 126 (2): 275-279.
Lee: Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. [[email protected]]
12534
Cornish-Bowden, A., Hofmeyr, J.-H.S. & Cárdenas, M.L., 2002. Stoicheiometric analysis in studies of metabolism. [T. brucei] Biochemical Society Transactions, 30 (2): 43-46.
Cornish-Bowden: Bioénergétique et Ingénierie des Protéines, Institut Fédératif "Biologie Structurale et Microbiologie", CNRS, 31 chemin Joseph-Aiguier, BP 71, 13402 Marseille Cedex 20, France. [[email protected]]
12535
Das, A. & Bellofatto, V., 2003. RNA polymerase II-dependent transcription in trypanosomes is associated with a SNAP complex-like transcription factor. Proceedings of the National Academy of Sciences of the United States of America, 100 (1): 80-85.
Bellofatto: Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey - New Jersey Medical School, International Center for Public Health, Newark, NJ 07103, USA. [[email protected]]
12536
De Luca, S., Ulhaq, S., Dixon, M.J., Essex, J. & Bradley, M., 2003. Solid-phase synthesis of a focused library of trypanothione reductase inhibitors. Tetrahedron Letters, 44 (15): 3195-3197.
Bradley: Department of Chemistry, University of Southampton, Southampton SO17 1BJ, UK.
A focused library of inhibitors of the enzyme trypanothione reductase was prepared using solid-phase synthesis. The inhibitors were based on a previously identified, non-competitive, lead compound comprising of two Pmc (2,2,5,7,8-pentamethylchroman-6-sulfonyl) side-chain protected, N-capped arginine residues linked by a spermidine bridge. In total six protecting groups and four capping groups were used to generate a 24-membered library. All compounds bearing the 5-methoxyindole-3-acetic acid capping group were found to have good activity. The most potent inhibitor was observed to contain the Mtr (4-methoxy-2,3,6-trimethylbenzenesulphonyl) protecting group on the arginine residue, terminated with tryptophan as the capping group.
12537
Fang, J. & Beattie, D.S., 2003. Identification of a gene encoding a 54 kDa alternative NADH dehydrogenase in Trypanosoma brucei. Molecular and Biochemical Parasitology, 127 (1): 73-77.
Beattie: Department of Biochemistry and Molecular Pharmacology, West Virginia University School of Medicine, P.O. Box 9142, Morgantown, WV 26506-9142, USA. [[email protected]]
12538
Fernandes, E.C., Granjeiro, J.M., Taga, E.M., Meyer-Fernandes, J.R. & Aoyama, H., 2003. Phosphatase activity characterization on the surface of intact bloodstream forms of Trypanosoma brucei. FEMS Microbiology Letters, 220 (2): 197-206.
Fernandes: Centro de Genética, Biologia Molecular e Fitoquímica, Instituto Agrônomico de Campinas, Av. Theodureto de A. Camargo 1500, 13.075-630 Campinas, SP, Brazil. [[email protected]]
12539
Flück, C., Salomone, J.Y., Kurath, U. & Roditi, I., 2003. Cycloheximide-mediated accumulation of transcripts from a procyclin expression site depends on the intergenic region. Molecular and Biochemical Parasitology, 127 (1): 93-97.
Roditi: Institut für Zellbiologie, Universität Bern, Balterstrasse 4, CH-3012 Bern, Switzerland. [[email protected]]
12540
Green, H.P., Portela, M.P.M., St Jean, E.N., Lugli, E.B. & Raper, J., 2003. Evidence for a Trypanosoma brucei lipoprotein scavenger receptor. Journal of Biological Chemistry, 278 (1): 422-427.
Raper: Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10010, USA. [[email protected]]
12541
Hamilton, C. J., Saravanamuthu, A., Eggleston, I. M. & Fairlamb, A. H., 2003. Ellman's-reagent-mediated regeneration of trypanothione in situ: substrate-economical microplate and time-dependent inhibition assays for trypanothione reductase. Biochemical Journal, 369 (3): 529-537.
Fairlamb: Division of Biological Chemistry & Molecular Microbiology, School of Life Sciences, Carnelley Building, University of Dundee, Dundee DD1 4HN, UK. [[email protected]]
12542
Hannaert, V., Saavedra, E., Duffieux, F., Szikora, J.-P., Rigden, D.J., Michels, P.A.M. & Opperdoes, F.R., 2003. Plant-like traits associated with metabolism of Trypanosoma parasites. Proceedings of the National Academy of Sciences of the United States of America, 100 (3): 1067-1071.
Opperdoes: Research Unit for Tropical Diseases and Laboratory of Biochemistry, Christian de Duve Institute of Cellular Pathology and Université Catholique de Louvain, B-1200 Brussels, Belgium. [[email protected]]
Trypanosomatid parasites cause serious diseases among humans, livestock, and plants. They belong to the order of the Kinetoplastida and form, together with the Euglenida, the phylum Euglenozoa. Euglenoid algae possess plastids capable of photosynthesis, but plastids are unknown in trypanosomatids. Here we present molecular evidence that trypanosomatids possessed a plastid at some point in their evolutionary history. Extant trypanosomatid parasites, such as Trypanosoma and Leishmania, contain several 'plant-like' genes encoding homologues of proteins found in either chloroplasts or the cytosol of plants and algae. The data suggest that kinetoplastids and euglenoids acquired plastids by endosymbiosis before their divergence and that the former lineage subsequently lost the organelle but retained numerous genes. Several of the proteins encoded by these genes are now, in the parasites, found inside highly specialized peroxisomes, called glycosomes, absent from all other eukaryotes, including euglenoids.
12543
Hillebrand, H., Schmidt, A. & Krauth-Siegel, R.L., 2003. A second class of peroxidases linked to the trypanothione metabolism. Journal of Biological Chemistry, 278 (9): 6809-6815.
Krauth-Siegel: Biochemie-Zentrum Heidelberg, Universität Heidelberg, 69120 Heidelberg, Germany. [[email protected]]
12544
Isobe, T., Holmes, E.C. & Rudenko, G., 2003. The transferrin receptor genes of Trypanosoma equiperdum are less diverse in their transferrin binding site than those of the broad-host range Trypanosoma brucei. Journal of Molecular Evolution, 56 (4): 377-386.
Rudenko: The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK. [gloria.rudenko @medawar.ox.ac.uk]
Trypanosoma brucei and T. equiperdum infect the mammalian bloodstream and tissues. Trypanosoma brucei is transmitted by tsetse flies within an extremely large range of mammals in sub-Saharan Africa. In contrast, T. equiperdum is restricted to equines, where it is transmitted as a venereal disease. Both species evade immune destruction by changing their variant surface glycoprotein (VSG), encoded in a telomeric VSG expression site. Trypanosoma brucei has about 20 VSG expression sites, and it has been proposed that their genetic diversity plays a role in host adaptation. Two expression site-associated genes ESAG6 and ESAG7, encode variable transferrin receptor subunits allowing trypanosomes to internalize polymorphic transferrin molecules from different mammals. We investigated if there was a correlation between the size of the trypanosome host range and the degree of ESAG6 genetic diversity. Both T. equiperdum and T. brucei appear to have approximately similar numbers of ESAG6; however, the genetic diversity of the ESAG6 family varies in the two species. We sequenced 114 T. equiperdum ESAG6 genomic clones, resulting in the isolation of ten T. equiperdum ESAG6 variants. The T. equiperdum ESAG6 genes were genetically less diverse than those of T. brucei in regions known to play a role in transferrin binding. This indicates that ESAG6 genetic diversity, playing a role in host adaptation, could have been lost in the absence of selection pressure. There was also evidence of positive selection (dN/dS = ~5) acting on other ESAG6 regions not involved in transferrin binding, perhaps due to antigenic variation of these surface molecules.
12545
Kabututu, Z., Martin, S. K., Nozaki, T., Kawazu, S., Okada, T., Munday, C. J., Duszenko, M., Lazarus, M., Thuita, L. W., Urade, Y. & Kubata, B. K., 2002. Prostaglandin production from arachidonic acid and evidence for a 9,11-endoperoxide prostaglandin H2 reductase in Leishmania. [T. brucei] International Journal for Parasitology, 32 (14): 1693-1700.
Kubata: Department of Molecular Behavioural Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
12546
Landfear, S.M., 2003. Trypanosomatid transcription factors: Waiting for Godot. Proceedings of the National Academy of Sciences of the United States of America, 100 (1): 7-9.
Landfear: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97201, USA. [[email protected]]
12547
Lébl, T., Smièka, A., Brus, J. & Bruhn, C., 2003. Synthesis, structural study, and in vitro trypanocidal and antitumour activities of tetrakis(3-methoxypropyl)tin and (3-methoxypropyl)tin chlorides. European Journal of Inorganic Chemistry, 2003 (1): 142-148.
Lébl: Department of General and Inorganic Chemistry, University of Pardubice, Cs Legii 565, Pardubice 53210, Czech Republic.
12548
Lemercier, G., Bakalara, N. & Santarelli, X., 2003. On-column refolding of an insoluble histidine tag recombinant exopolyphosphatase from Trypanosoma brucei overexpressed in Escherichia coli. Journal of Chromatography B - Analytical Technologies in the Biomedical and Life Sciences, 786 (1-2): 305-309.
Santarelli: Ecole Supérieure de Technologie des Biomolécules de Bordeaux (ESTBB), Université Victor Segalen Bordeaux 2, 146 Rue Léo Saignat, 33076 Bordeaux cedex, France. [[email protected]]
12549
Lillico, S., Field, M.C., Blundell, P., Coombs, G.H. & Mottram, J.C., 2003. Essential roles for GPI-anchored proteins in African trypanosomes revealed using mutants deficient in GP18. Molecular Biology of the Cell, 14 (3): 1182-1194.
Mottram: Wellcome Centre for Molecular Parasitology, University of Glasgow, The Anderson College, Glasgow G11 6NU, UK. [[email protected]]
12550
Lorger, M., Engstler, M., Homann, M. & Göringer, H. U., 2003. Targeting the variable surface of African trypanosomes with variant surface glycoprotein-specific, serum-stable RNA aptamers. Eukaryotic Cell, 2 (1): 84-94.
Göringer: Department of Genetics and Microbiology, Darmstadt University of Technology, Schnittspahnstrasse 10, D-64287 Darmstadt, Germany.
12551
Martin, W. & Borst, P., 2003. Secondary loss of chloroplasts in trypanosomes. [Editorial essay] Proceedings of the National Academy of Sciences of the United States of America, 100 (3): 765-767.
Martin: Institute of Botany III, Universität Düsseldorf, Universitätstrasse 1, D-40225 Düsseldorf, Germany. [[email protected]]
12552
Mehlert, A, Bond, C.S. & Ferguson, M.A.J., 2002. The glycoforms of a Trypanosoma brucei variant surface glycoprotein and molecular modeling of a glycosylated surface coat. Glycobiology, 12 (10): 607-612.
Ferguson: Division of Biological Chemistry and Molecular Biology, The Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK. [[email protected]]
12553
Millet, R., Maes, L., Landry, V., Sergheraert, C. & Davioud-Charvet, E., 2002. Antitrypanosomal activities and cytotoxicity of 5-nitro-2-furancarbohydrazides. [T. brucei] Bioorganic & Medicinal Chemistry Letters, 12 (24): 3601-3604.
Davioud-Charvet: UMR 8525 CNRS, Université de Lille 2, Institut de Biologie de Lille et Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 447, F-59021, Lille, France. [[email protected]]
12554
Mussmann, R., Janssen, H., Calafat, J., Engstler, M., Ansorge, I., Clayton, C. & Borst, P., 2003. The expression level determines the surface distribution of the transferrin receptor in Trypanosoma brucei. Molecular Microbiology, 47 (1): 23-35.
Borst: Divisions of Molecular Biology and Cell Biology, and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. [[email protected]]
12555
Nihei, C., Fukai, Y., Kawai, K., Osanai, A., Yabu, Y., Suzuki, T., Ohta, N., Minagawa, N., Nagai, K. & Kita, K., 2003. Purification of active recombinant trypanosome alternative oxidase. FEBS Letters, 538 (1-3): 35-40.
Kita: Department of Biomedical Chemistry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. [[email protected]]
12556
Nok, A. J. & Nock, I. H., 2002. Transferrin coupled azanthraquinone enhances the killing effect on trypanosomes. The role of lysosomal mannosidase. Parasite, 9 (4): 375-379.
Nok: Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria. [[email protected]]
12557
Nok, A.J., Nock, I.H. & Bonire, J.J., 2003. The cholesterol pathway of Trypanosoma congolense could be a target for triphenyltinsalicylate and triphenylsiliconsalicylate inhibition. Applied Organometallic Chemistry, 17 (1): 17-22.
Nok: Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria. [[email protected]]
12558
Okano, Y., Inoue, T., Kubata, B.K., Kabututu, Z., Urade, Y., Matsumura, H. & Kai, Y., 2002. Crystallization and preliminary X-ray crystallographic studies of Trypanosoma brucei prostaglandin F2á synthase. Journal of Biochemistry, 132 (6): 859-861.
Kai: Department of Materials Chemistry, Graduate School of Engineering, Osaka University, Yamada-oka 2-1, Suita, Osaka 565-0871, Japan. [[email protected]]
12559
Pasti, C., Rinaldi, E., Cervellati, C., Dallocchio, F., Hardré, R., Salmon, L. & Hanau, S., 2003. Sugar derivatives as new 6-phosphogluconate dehydrogenase inhibitors selective for the parasite Trypanosoma brucei. Bioorganic and Medicinal Chemistry, 11 (7): 1207-1214.
Hanau: Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Via L. Borsari 46, 44100, Ferrara, Italy.
12560
Paugam, A., Bulteau, A. L., Dupouy-Camet, J., Creuzet, C. & Friguet, B., 2003. Characterization and role of protozoan parasite proteasomes. [Trypanosoma] Trends in Parasitology, 19 (2): 55-59.
Paugam: Laboratoire Signalisation et Parasites (EA 3623), Université Paris 5, C.H.U. Cochin, 27, rue du Faubourg Saint Jacques 75014 Paris, France. [andre. [email protected]]
The proteasome, a large non-lysosomal multi-subunit protease complex, is ubiquitous in eukaryotic cells. In protozoan parasites, the proteasome is involved in cell differentiation and reproduction, and could therefore be a promising therapeutic target. This article reviews the present knowledge on the proteasomes in protozoal parasites of medical importance, such as Giardia, Entamoeba, Leishmania, Trypanosoma, Plasmodium and Toxoplasma spp.
12561
Rasooly, R. & Balaban, N., 2002. Structure of p15 trypanosome microtubule associated protein. Parasitology Research, 88 (12): 1034-1039.
Rasooly: Department of Nutrition, University of California, Davis, One Shields Avenue, Meyer Hall Room 3135, Davis CA 95616, USA. [[email protected]]
12562
Roberts, C.W., McLeod, R., Rice, D.W., Ginger, M. Chance, M.L. & Goad, L.J., 2003. Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa. Molecular and Biochemical Parasitology, 126 (2): 129-142.
Roberts: Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Glasgow G4 0NR, UK. [c.w.roberts @strath.ac.uk]
12563
Scharsack, J.P., Steinhagen, D., Kleczka, C., Schmidt, J.O., Korting, W., Michael, R.D., Leibold, W. & Schuberth, HJ., 2003. The haemoflagellate Trypanoplasma borreli induces the production of nitric oxide, which is associated with modulation of carp (Cyprinus carpio L.) leucocyte functions. [T. brucei] Fish and Shellfish Immunology, 14 (3): 207-222.
Steinhagen: Hannover School of Veterinary Medicine, Fish Diseases Research Unit, PO Box 711180, D-30545 Hannover, Germany.
12564
Schimanski, B., Klumpp, B., Laufer, G., Marhöfer, R.J. Selzer, P.M. & Günzl, A., 2003. The second largest subunit of Trypanosoma brucei's multifunctional RNA polymerase I has a unique N-terminal extension domain. Molecular and Biochemical Parasitology, 126 (2): 193-200.
Günzl: Medizinisch-Naturwissenschaftliches Forschungszentrum, Ob dem Himmelreich 7, 72074 Tübingen, Germany. [[email protected]]
12565
Shaw, M.P., Bond, C.S., Roper, J.R., Gourley, D.G., Ferguson, M.A.J. & Hunter, W.N., 2003. High-resolution crystal structure of Trypanosoma brucei UDP-galactose 4?-epimerase: a potential target for structure-based development of novel trypanocides. Molecular and Biochemical Parasitology, 126 (2): 173-180.
Hunter: Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. [[email protected]]
12566
Shi, M.Q., Pan, W.L. & Tabel, H., 2003. Experimental African trypanosomiasis: IFN-ã mediates early mortality. [mice] European Journal of Immunology, 33 (1): 108-118.
Tabel: Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4 Canada. [[email protected]]
12567
Steenkamp, D.J., 2002. Trypanosomal antioxidants and emerging aspects of redox regulation in the trypanosomatids. Antioxidants and Redox Signalling, 4 (1): 105-121.
Steenkamp: Department of Laboratory Medicine, Division of Chemical Pathology, School of Medicine, University of Cape Town, ZA-7925 Observatory, South Africa.
12568
Vanhamme, L., Paturiaux-Hanocq, F., Poelvoorde, P., Nolan, D.P., Lins, L., Van den Abbeele, J., Pays, A., Tebabi, P., Van Xong, H., Jacquet, A., Moguilevsky, N., Dieu, M. & Pays, E., 2003. Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature, 422 (6927): 83-87.
Pays: Laboratory of Molecular Parasitology, IBMM, University of Brussels, 12 rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium. [[email protected]]
Human sleeping sickness in east Africa is caused by the parasite Trypanosoma brucei rhodesiense. The basis of this pathology is the resistance of these parasites to lysis by normal human serum (NHS). Resistance to NHS is conferred by a gene that encodes a truncated form of the variant surface glycoprotein termed serum resistance associated protein (SRA). We show that SRA is a lysosomal protein, and that the amino-terminal á-helix of SRA is responsible for resistance to NHS. This domain interacts strongly with a carboxy-terminal á-helix of the human-specific serum protein apolipoprotein L-I (apoL-I). Depleting NHS of apoL-I, by incubation with SRA or anti-apoL-I, led to the complete loss of trypanolytic activity. Addition of native or recombinant apoL-I either to apoL-I-depleted NHS or to fetal calf serum induced lysis of NHS-sensitive, but not NHS-resistant, trypanosomes. Confocal microscopy demonstrated that apoL-I is taken up through the endocytic pathway into the lysosome. We propose that apoL-I is the trypanosome lytic factor of NHS, and that SRA confers resistance to lysis by interaction with apoL-I in the lysosome.
12569
Vial, H.J., Eldin, P., Tielens, A.G.M. & van Hellemond, J.J., 2003. Phospholipids in parasitic protozoa. Molecular and Biochemical Parasitology, 126 (2): 143-154.
Vial: Dynamique Moléculaire des Interactions Membranaires, CNRS UMR 5539, cc107, Université Montpellier II, Place Eugène Bataillon, 34095 Montpellier, France. [[email protected]]
