[S and C hemoglobinopathies and serum IgM. Relationship observed in the areas of endemic trypanosomiasis. Studies in areas without trypanosomiasis].
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Blood Protein Electrophoresis↗
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Twentieth seminar on trypanosomiasis. Trypanosomiasis Advisory Panel of the Overseas Development Administration. September 1979. Abstracts.
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Humans↗
Modelling trypanosomiasis prevalence and periodic epidemics and epizootics.
Existing mathematical models of trypanosomiasis epidemiology and epizootiology are extended by including some relevant biology of the disease vector, the tsetse fly. Rickettsia-like organisms, or RLO, are a vertically transmitted symbiont of tsetse, which confer an increased susceptibility to trypanosomiasis infection. Tsetse populations are also limited by density-dependent starvation. Modelling leads to the prediction of a stable dimorphism with a fraction of tsetse possessing RLO. The equilibrium prevalence of trypanosomiasis in the vertebrate hosts is no longer in RLO models determined simply by such traditional parameters as vectorial capacity. Only the RLO-positive tsetse carry infection, and their number is itself regulated by trypanosomiasis prevalence. The result of a naive model is that controlling tsetse numbers does not decrease prevalence until all tsetse are RLO-positive. However, under the density-dependent starvation model derived in this paper, the relative mortality of RLO-positive flies is greater at lower tsetse numbers. This tips the balance towards lower equilibrium prevalence of trypanosomiasis as tsetse numbers are decreased. The presence of RLO also gives rise to long-term oscillations in trypanosomiasis prevalence in humans and animals. However, when another mechanism that can also cause periodic epizootics (of shorter periodicity) is included, namely host immunity, the two epizootic processes combine to produce periodic epizootics (and therefore epidemics) at a single frequency. There are two decaying modes, one in which the tsetse population size quickly reaches equilibrium in a few weeks, and a second very slowly decaying mode in which host immunity and RLO effects interact. The equilibrium reached is shown to be asymptotically stable. In view of the seeming importance of RLO in trypanosomiasis epidemiology, it is important that field biologists enable RLO models to be validated by measuring the proportion of tsetse with RLO, in conjunction with vector density and trypanosomiasis prevalence and incidence in tsetse and vertebrate hosts.
Animals↗
Participatory investigations of bovine trypanosomiasis in Tana River District, Kenya.
Participatory research on bovine trypanosomiasis was conducted with Orma pastoralists in Tana River District, Kenya. The use of participatory methods to understand local perceptions of disease signs, disease causes, disease incidence by cattle age group, seasonal patterns of disease and preferences for indigenous and modern control methods are described. Results indicated that local characterization of diseases called gandi and buku by Orma pastoralists was similar to modern veterinary knowledge on chronic trypanosomiasis and haemorrhagic trypanosomiasis (due to Trypanosoma vivax), respectively. The mean incidence of gandi varied from 10.2% in calves to 28.6% in adult cattle. The mean incidence of buku varied from 3.1% in calves to 9.6% in adults. Pearson correlation coefficients for disease incidence by age group were 0.498 (P < 0.01) and 0.396 (P < 0.05) for gandi and buku, respectively. Informants observed cases of trypanosomiasis in 24.1% of cattle (all age groups); these cases accounted for 41.8% of all sick cattle during the preceding 12-month period. Eight indigenous and three modern trypanosomiasis control methods were identified. Results indicated that an integrated approach to trypanosomiasis control based on private, individual action was well established in the assessment area. When presented with four different trypanosomiasis control methods, community representatives selected 'better use of trypanocides' as the most preferred intervention and 'community-based tsetse control' as the least preferred intervention. This finding prompted researchers to modify the original project activities. Constraints facing the sustainability of community-based tsetse control are discussed.
Age Factors↗
The epidemiology and control of human African trypanosomiasis.
Human African trypanosomiasis is caused by Trypanosoma brucei gambiense in West and Central Africa, and by Trypanosoma brucei rhodesiense in East and southern Africa. In recent years there has been a dramatic resurgence of Gambian trypanosomiasis in Central Africa, especially in the Democratic Republic of Congo, Angola and Sudan. The disease is quiescent in most of West Africa, as is Rhodesian trypanosomiasis the other side of the continent. The epidemiology of Gambian trypanosomiasis is reviewed in detail. The long duration of infection in human hosts with cycles of intermittent parasitaemia, the vectors' feeding habits and the intensity of human-fly contact are the major determinants of the dynamics of transmission of this parasite. The development of immunity may lead to a reduction in the fraction of the population that is susceptible to infection and the burning out of epidemics after 20 to 30 years. So far, the acquired immune deficiency syndrome pandemic has had no impact on the epidemiology of Gambian trypanosomiasis. A brief review of the epidemiology of Rhodesian trypanosomiasis highlights the differences from Gambian trypanosomiasis that, to some extent, explain its lower propensity to cause epidemics: it is a more aggressive disease that rapidly kills its human host, and its transmission involves mostly domestic and game animals, humans being in most circumstances an accidental host. The various methods and strategies for the surveillance and control of both diseases are reviewed.
Africa↗
Susceptibility to African trypanosomiasis of N'Dama and Zebu cattle in an area of Glossina morsitans submorsitans challenge.
The use of trypanotolerant livestock is considered to be an important strategy for the control of African animal trypanosomiasis. In order to define the extent of the differences in susceptibility and productivity, 10 Zebu cows (a breed considered trypanosusceptible) and 10 N'Dama cows (a breed recognised for trypanotolerance) were exposed to a natural field challenge from Glossina morsitans submorsitans Newstead. The animals were two-and-a-half to three years old and had not been previously exposed to trypanosomiasis. All Zebu died of trypanosomiasis within eight months of first exposure. In contrast, only three N'Dama died of trypanosomiasis; they had all been suckling calves before they succumbed 11 to 14 months after initial exposure. The prevalence, level and duration of parasitaemia were significantly less in the N'Dama, which, unlike the Zebu, did not become febrile during parasitaemia. The differences in parasitaemia were largely attributable to Trypanosoma vivax. The N'Dama also developed much less severe anaemia than the Zebu. The mean and standard deviation of the packed red cell volume of the N'Dama was not significantly different between eight months after exposure when all Zebu were dead, and 21 months when the experiment was terminated. The relative productivity of the N'Dama was impressive. In addition to reduced mortality, the N'Dama experienced no abortions and produced five calves, three of which were alive at the end of the experiment, at which time three of the surviving N'Dama were pregnant. In the Zebu, in marked contrast, abortions occurred both in early and late pregnancy and no live calves were produced. The study confirmed that N'Dama cattle are innately less susceptible to trypanosomiasis than Zebu cattle and can survive and be productive in endemic areas of trypanosomiasis where Zebu perish.
Animals↗
In vitro induction of microglial and endothelial cell apoptosis by cerebrospinal fluids from patients with human African trypanosomiasis.
In human African trypanosomiasis, trypanosomes first develop in the blood and lymph (Stage 1), then spread to the central nervous system (CNS) (Stage 2). Disruption of the blood-brain barrier of unknown mechanism occurs in Stage 2 disease. The hypothesis that cerebrospinal fluids (CSF) from African trypanosomiasis patients might contain factor(s) able to induce apoptosis in endothelial cells led us to evaluate this effect by two methods, the TdT-mediated dUTP nick end labelling (TUNEL) method and the measurement of soluble nucleosomes released by apoptotic cells in culture supernatant by ELISA. Apoptosis induction by CSF was also studied with microglial cells, the resident macrophages in the brain, which participate in the blood-brain barrier in the perivascular area. In contrast with control CSF, African trypanosomiasis patients' CSF induced apoptosis in both microglial and endothelial cells. The results obtained with the two methods correlated well, and showed that Stage 2 CSF induced apoptosis at higher levels in microglial cells, whereas the disease stage was not decisive for apoptosis induction in endothelial cells. We measured soluble Fas ligand (sFasL) and anti-Fas antibodies levels, two potent inducers of the Fas signalling pathway leading to apoptosis, in CSF from African trypanosomiasis patients and controls. CSF from African trypanosomiasis patients contained sFasL, and anti-Fas antibodies at higher levels than in controls. Stage 2 CSF contained more sFasL than Stage 1 CSF, and anti-Fas antibodies were detected only in Stage 2 CSF. Caspase-8 inhibitor effect and statistical data suggest that other pro-apoptotic factors may be involved in some CSF-induced apoptosis. Apoptosis induction may participate in the pathogenesis during African trypanosomiasis, and the presence of sFasL and anti-Fas antibodies may provide new tools for diagnosis and prognosis of the disease.
Animals↗
Impact of nutrition on the pathophysiology of bovine trypanosomiasis.
Trypanosomiasis is a major veterinary problem over much of sub-Saharan Africa and is frequently associated with under-nutrition. There is growing evidence that nutrition can have a profound effect on the pathophysiological features of animal trypanosomiasis. These features include anaemia, pyrexia, body weight changes, reduced feed intake and diminished productivity including reduced draught work output, milk yield and reproductive capacity. Anaemia is a principal characteristic of trypanosomiasis and the rate at which it develops is influenced by both protein and energy intakes. Pyrexia is associated with increased energy demands for maintenance which is ultimately manifested by reductions in voluntary activity levels and productivity. Weight changes in trypanosomiasis are markedly influenced by the levels of protein intake. High intakes allow infected animals to grow at the same rate as uninfected controls providing energy intake is adequate whilst low energy levels can exacerbate the adverse effects of trypanosomiasis on body weight. Reductions in feed intake are less apparent in animals which are provided with high protein diets and where intake is limited by the disease animals will often exhibit preferential selection of higher quality browse. Further studies are required to evaluate the minimum levels of protein and energy supplementation required to ameliorate the adverse effect of trypanosomiasis, the nature and quality of protein supplement to achieve these benefits and the influence these have on digestive physiology.
Animal Nutritional Physiological Phenomena↗
Cutaneous manifestations of African trypanosomiasis.
BACKGROUND: Dermatologists may evaluate patients with African trypanosomiasis. The currently available dermatologic literature does not review the cutaneous manifestations of African trypanosomiasis. OBSERVATION: We describe an American man who acquired African trypanosomiasis while hunting in Tanzania, and we review and classify the cutaneous findings of this disease. This article reports the results of the first biopsy of a trypanid and depicts trypanosomes on the first touch preparation done from a trypanid biopsy specimen. Rare color photographs of trypanids are shown. CONCLUSIONS: Recognition of the unique cutaneous manifestations of African trypanosomiasis may allow dermatologists to make a rapid diagnosis that is essential for timely treatment and survival. Classifying the disease with primary chancriform, secondary hemolymphatic, and tertiary central nervous system stages should improve the understanding of the complex natural history of African trypanosomiasis.
Aged↗
A simple epidemiological method for animal trypanosomiasis to provide relevant data for effective financial decision-making.
The epidemiology of bovine trypanosomiasis on Galana Ranch, Kenya was studied for one year (July 1980--June 1981), using measurements from an experimental population of 3 types of Boran cattle. The results were applied to the estimated ranch population at risk, and an attempt was made to measure the potential economic loss due to trypanosomiasis. The potential losses in beef production due to trypanosomiasis in the ranch population at risk at Galana were estimated at around K.Shs. 8900/km2, when the stocking rate was 14.2 Tropical Livestock Units per km2. The estimated potential loss in the total population at risk was approximately K.Shs. 5 million (around US$ 700,000 at 1981 values). These losses can be minimised by good management techniques based on accurate epidemiological information. Results indicated that Orma-type Boran steers are more resistant to trypanosomiasis than Galana-type Boran steers. Although both types showed similar mortality rates, untreated Orma animals which survived showed a similar growth performance to animals maintained under 3-month Samorin prophylaxis. Untreated Galana Borans lost 14% of their body weight when compared with animals maintained under 3-month Samorin. Also, 30% of the untreated Orma Borans never showed trypanosomes in their blood over the study period, while all corresponding Galana Borans showed parasites; this resulted in a lower measured attack rate in Orma cattle. In 1982, a combination of treating only those animals under trypanosome attack, relating the timing of chemotherapy to measured increased trypanosome attack, and the increased utilisation of the trypano-tolerant Orma Borans resulted in an annual saving of around US$ 110,000 in control costs and an increased land usage of approximately 5%.
Age Factors↗
Identification and selection of cattle naturally resistant to African trypanosomiasis.
Cattle were exposed to natural trypanosome challenge in an area of high Glossina density (Samandéni, Burkina Faso) for various periods of time during 1982, 1983, 1984 and 1985. All of 30 Zebu proved to be sensitive to trypanosomiasis i.e. they died or were treated in extremis in 10 +/- 4 weeks. Twenty-one (31%) Baoulé were as sensitive as the Zebu while 47 (69%) were resistant i.e. they survived in good condition. Twenty Ndama/Baoulé crosses, indigenous to Samandéni were all resistant. Weekly blood samples were taken (2,317 in total) for the determination of parasitaemia and packed cell volume (PCV) as a measure of anaemia, the most important pathological feature of cattle trypanosomiasis. In both Zebu and sensitive Baoulé 59% of the blood samples showed positive parasitaemia, of which 38% and 52% respectively were T. congolense the major cattle pathogen in the area considered. In resistant Baoulé and Ndama/Baoulé 11% and 10% of the samples were positive for trypanosomes of which only 4% and 2% were T. congolense respectively. PCV decreased from 35 to 20 in Zebu, 39 to 20 in sensitive Baoulé and 40 to 34 in resistant Baoulé, there was no change in the indigenous Ndama/Baoulé. Six Ndama/Baoulé indigenous to Samandéni remained resistant to trypanosomiasis when moved to another area of high Glossina challenge. Seven Ndama/Baoulé calves, conceived in Samandéni but born and kept for 2 1/2 years in a Glossina-free area, also proved to be resistant to challenge. Twelve Baoulé calves, born from cattle selected under natural field challenge, and which had not come in contact with trypanosomes for the first 10 months of their life, proved to be resistant when exposed in the field. These observations show that some, but not all, cattle from the Baoulé breed are naturally resistant to African trypanosomiasis, that this resistance does not need repeated exposure to trypanosomes early in life but appears to be inherited and functional against many types of antigenically different trypanosomes. Thus, selective breeding of trypanoresistant animals and their successful introduction, without trypanocidal drug protection, into areas of high Glossina density appears feasible.
Animals↗
Some principles of the immunology of trypanosomiasis.
Although immunological methods have not been used on a wide scale for the study of trypanosomiasis in Africa, there is hope that immunological research will lead to improved methods of diagnosis, methods for the classification of trypanosome strains, better understanding of the epidemiology, epizootiology and pathology of trypanosomiasis, and ultimately the development of methods of immunization against the disease.This paper reviews some of the problems that hinder progress in each of these areas. Such problems include inadequacies in existing methods of obtaining antigens of Trypanosoma vivax, T. congolense, and T. gambiense; the general lack of fundamental information on the nature and properties of trypanosome antigens; and the variability of certain trypanosome antigens in infected animals. Recent progress towards the solution of these problems is summarized, and aspects of the immunology of trypanosomiasis that require further study are discussed. These include the diagnostic value of determinations of IgM globulin levels; the properties of T. vivax and T. congolense antigens; the natural immunity of game animals and certain varieties of cattle to trypanosomiasis; and the possibility of immunizing livestock by exposing drug-treated animals to a continuous low-grade trypanosome challenge.
Africa↗
Evaluation of an antigen detection-ELISA test for the diagnosis of trypanosomiasis in naturally infected cattle.
The sensitivity and the specificity of the antigen detection ELISA proposed by Nantulya and Lindqvist (1989) for the diagnosis of African Animal Trypanosomiasis have been assessed in naturally-occurring infections. 1633 cattle were sampled in trypanosomiasis endemic area and examined for trypanosomes by darkground/phase contrast buffy-coat method described by Murray et al. (1977) and for circulating antigen by ELISA. Fifty sera from Markoye, a tsetse free area in north of Burkina Faso, and 49 sera from Germany were also tested. In trypanosomiasis infested area, BCT detected 144 (8.8%) positive animals while Ag-ELISA revealed 65.8% of positive. Out of the 144 BCT-parasite-positive, Ag-ELISA enable to detect 75% of positive. The predominant trypanosomes identified by BCT was Trypanosoma vivax followed by T. congolense while Ag-ELISA indicated T. congolense followed by T. brucei. Ag-ELISA detected 76.5% out of the 51 T. congolense-BCT-positive and only 17% of all T. vivax BCT-positive. Cattle carring mixed infection involving two or three trypanosomes, particularly those with T. brucei and T. congolense are the most frequent. In tsetse free area, Ag-ELISA detected one positive cattle carring T. brucei and T. congolense and showed an apparent specificity of 98%. No serum from Germany was detected positive. This study suggests the joint use of Ag-ELISA and BCT for the diagnosis of trypanosomiasis particularly in epidemiological study in endemic area.
Animals↗
Studies on the epidemiology of trypanosomiasis in sheep and goats in Kenya.
The epidemiology of trypanosomiasis in a tsetse-infested range area of Kenya was studied for 2 years in various breeds of sheep and goats. Observations, including infection rates, PCV, temperature and weight loss indicated that the exotic breeds were more susceptible to natural trypanosomal infection than the indigenous breeds and that the infection may be severely debilitating and in many cases fatal. Observations of tsetse numbers and rainfall in the grazing area during the first year showed that there was a significant correlation between tsetse numbers and rainfall of the previous month. The increase in tsetse numbers, which occurred one month after substantial rainfall, was followed by an increase in the prevalence of trypanosomiasis in the animals. However, during the second year when rainfall was low there was no correlation between tsetse numbers and rainfall. It was concluded that the seasonal incidence of trypanosomiasis and the possible trypanotolerance of the indigenous breeds are important factors to be considered when initiating a small stock improvement programme for trypanosomiasis-endemic areas.
Animals↗
Diagnostic and neuropathogenesis issues in human African trypanosomiasis.
Human African trypanosomiasis, also known as sleeping sickness, is caused by protozoan parasites of the genus Trypanosoma, and is a major cause of human mortality and morbidity. The East African and West African variants, caused by Trypanosma brucei rhodesiense and Trypanosoma brucei gambiense, respectively, differ in their presentation but the disease is fatal if untreated. Accurate staging of the disease into the early haemolymphatic stage and the late encephalitic stage is critical as the treatment for the two stages is different. The only effective drug for late stage disease, melarsoprol, which crosses the blood-brain barrier, is followed by a severe post-treatment reactive encephalopathy in 10% of cases of which half die. There is no current consensus on the diagnostic criteria for CNS involvement and the specific indications for melarsoprol therapy also differ. There is a pressing need for a quick, simple, cheap and reliable diagnostic test to diagnose Human African trypanosomiasis in the field and also to determine CNS invasion. Cerebrospinal fluid and plasma analyses in patients with Human African trypanosomiasis have indicated a role for both pro-inflammatory and counter-inflammatory cytokines in determining the severity of the meningoencephalitis of late stage disease, and, at least in T. b. rhodesiense infection, the balance of these opposing cytokines may be critical. Rodent models of Human African trypanosomiasis have proved very useful in modelling the post-treatment reactive encephalopathy of humans and have demonstrated the central role of astrocyte activation and cytokine balances in determining CNS disease. Such animal models have also allowed a greater understanding of the more direct mechanisms of trypanosome infection on CNS function including the disruption of circadian rhythms, as well as the immunological determinants of passage of trypanosomes across the blood-brain barrier.
Animals↗
A novel and accurate diagnostic test for human African trypanosomiasis.
INTRODUCTION: 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 can diagnose human African trypanosomiasis with high sensitivity and specificity. METHODS: We applied serum samples from 85 patients with African trypanosomiasis and 146 control patients who had other parasitic and non-parasitic infections to a weak cation exchange chip, and analysed with surface-enhanced laser desorption-ionisation 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. FINDINGS: 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% and 98.6%, respectively, when the majority opinion of the three algorithms was considered. This novel approach is much more accurate than any other diagnostic test. INTERPRETATION: Our 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 for improving the accuracy of patient recruitment in large-scale epidemiological studies.
Adolescent↗
Treatment of human African trypanosomiasis--present situation and needs for research and development.
Human African trypanosomiasis re-emerged in the 1980s. However, little progress has been made in the treatment of this disease over the past decades. The first-line treatment for second-stage cases is melarsoprol, a toxic drug in use since 1949. High therapeutic failure rates have been reported recently in several foci. The alternative, eflornithine, is better tolerated but difficult to administer. A third drug, nifurtimox, is a cheap, orally administered drug not yet fully validated for use in human African trypanosomiasis. No new drugs for second-stage cases are expected in the near future. Because of resistance to and limited number of current treatments, there may soon be no effective drugs available to treat trypanosomiasis patients, especially second-stage cases. Additional research and development efforts must be made for the development of new compounds, including: testing combinations of current trypanocidal drugs, completing the clinical development of nifurtimox and registering it for trypanosomiasis, completing the clinical development of an oral form of eflornithine, pursuing the development of DB 289 and its derivatives, and advancing the pre-clinical development of megazol, eventually engaging firmly in its clinical development. Partners from the public and private sector are already engaged in joint initiatives to maintain the production of current drugs. This network should go further and be responsible for assigning selected teams to urgently needed research projects with funds provided by industry and governments. At the same time, on a long term basis, ambitious research programmes for new compounds must be supported to ensure the sustainable development of new drugs.
Africa South of the Sahara↗
P75 tumor necrosis factor-receptor shedding occurs as a protective host response during African trypanosomiasis.
In experimental murine trypanosomiasis, resistance is often scored as the capacity to control peak parasitemia levels, which results in prolonged survival. Infection-induced pathology has not systematically been used as a resistance criterion. Because this parameter could be the most relevant for comparative analysis of natural and experimental infections, as well as for understanding of pathology-associated immune alterations, we analyzed Trypanosoma brucei infections in 4 different established conventional mouse models, as well as in tumor necrosis factor (TNF)-deficient and TNF-receptor-deficient mice. Results indicate the following: (1) there is no correlation between peak parasitemia control or survival and the induction of infection-associated anemia, loss of body weight, liver pathology, reduced locomotor activity, and general morbidity; (2) serum levels of TNF, interferon- gamma, and interleukin-10, which are known to affect survival, do not correlate with induction of pathology; and (3) infection-induced occurrence of lipopolysaccharide hypersensitivity does not correlate with survival. However, one parameter that was found to correlate with the inhibition of trypanosomiasis-associated pathology in all models was the shedding of soluble p75 TNF-receptor during peak parasitemia stages. These results are important for future cytokine and trypanosomiasis pathology studies, because the interplay between TNF and the soluble receptors it sheds has not been considered in either human clinical sleeping sickness studies or in veterinary trypanosomiasis research.
Animals↗