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PubMed1993

Combination chemotherapy of CNS trypanosomiasis.

The progress which has been made in the treatment of experimental CNS trypanosomiasis with combination chemotherapy is reviewed. The most significant has been the use of four specific 5-nitroimidazoles in combination with either suramin or the arsenicals. The latter combination of MK 436 and Mel Cy, producing a rapid cure of CNS trypanosomiasis with only a two dose regimen and thus, would make an ideal universal treatment for both early- and late-stage trypanosomiasis. However, the 5-nitroimidazoles, because they are Ames' positive, are unlikely to be developed for use in humans. The combination chemotherapeutic regimen of eflornithine and arsenicals would allow the use of reduced quantities of melarsoprol to be used with similar or increased efficacy. As these drugs are already approved for use in humans, they could be applied immediately to the human disease; however, the quantities of eflornithine required for cures and the basic cost of this compound may limit its use in human medicine. Investigations of the post-treatment reactive encephalopathies (PTRE) which occur after non-curative treatment of trypanosome infections have shown that they are essentially caused by the presence of a residual focus of living trypanosomes in the CNS. If all trypanosomes are eliminated from the CNS (curative treatment) then there are no PTRE and when non-curative treatment is used the reaction can be reduced or ameliorated by supportive treatment with anti-inflammatory drugs such as prednisolone, dexamethasone or azathioprine.

Arsenicals↗

PubMed1984

Socio-economic problems related to animal trypanosomiasis in Africa.

Animal trypanosomiasis is one of the major constraints of rural development in Africa. If trypanosomiasis did not exist in these areas, it is estimated that some regions could carry 3-5 times more livestock. Chemotherapy and chemoprophylaxis are old methods used to tackle the problem and are still valuable, provided the number of interventions is limited. Tse-tse fly control is a very useful tool to combat trypanosomiasis but expensive. The sterile male release technique is not economically feasible on a wide scale. Immunization or vaccination is not yet available. Trypanotolerance is a biological phenomenon; it seems to be a valid method, which allow African countries to keep and increase livestock within economically feasible conditions; but inevitably it will be a long exercise.

Africa↗

PubMed2003

Cattle owners' perceptions of African bovine trypanosomiasis and its control in Busia and Kwale Districts of Kenya.

A study using a structured questionnaire was conducted in Busia District, Western Kenya and Kwale District, Coastal Kenya to obtain qualitative and quantitative information from 256 cattle owners about their production systems, their perceptions of the diseases encountered in their cattle, the drugs used, and other measures adopted to control trypanosomiasis in cattle. The predominant production system was mixed crop-livestock with farmers owning 2-11 local cattle on holdings between 2 and 5 ha. Approximately 15% of disease episodes in cattle were perceived to be trypanosomiasis, although the farmers' ability to make diagnoses was limited in that over half of the diagnoses were inconsistent with the clinical signs described. Drugs were generally obtained from agro-veterinary shops, and the farmers themselves administered slightly more than half of these. One third of drug treatments given to sick cattle were trypanocides, but over half of these trypanocidal treatments were given to cattle believed to have diseases other than trypanosomiasis.

Agriculture↗

PubMed2001

African trypanosomiasis research: 100 years of progress, but questions and problems still remain.

Past and present progress in our understanding of African trypanosomiasis is briefly reviewed. Although tremendous scientific strides have been achieved, an epidemic of the disease is currently underway. Three areas of research which are believed necessary for the control of African trypanosomiasis are discussed. It is suggested that a better understanding of the host-parasite relationship is essential; more emphasis and a broader approach to drug development is required; and finally, further research into the socio-economic aspects of African trypanosomiasis is urgently needed before the human disease can again be controlled.

Africa South of the Sahara↗

PubMed2002

Natural immunity to human African trypanosomiasis: trypanosome lytic factors and the blood incubation infectivity test.

This review focuses on the epidemiology of human African trypanosomiasis: why it occurs in humans, the current methods of surveillance, and the drugs available to treat it. Emphasis is placed on the identification of human-infective trypanosomes by the blood incubation infectivity test. This test distinguishes between trypanosomes that are non-infective for humans and those that are potentially infective. Currently the test requires incubation of parasites with human serum before injection into mice; any surviving parasites are considered human-infective. The factors in serum that kill all non-human-infective parasites are known as trypanosome lytic factors. The paper details the biochemistry of these factors and recommends standardization of the test based on current knowledge. This test can be used to screen animals with trypanosomiasis, in order to evaluate their role during endemic and epidemic human African trypanosomiasis.

Animals↗

PubMed2001

Options for vector control against trypanosomiasis in Africa.

Tsetse control has long been an important option for reducing the impact of African trypanosomiasis but, although many effective methods have been used, the results have seldom proved sustainable. Developments to reduce cost and environmental impact increasingly limit the choices available for control and the scale of operations has declined. Conversely, human trypanosomiasis has reached epidemic proportions in some countries. Here, Reg Allsopp argues that those tasked with managing trypanosomiasis or committed to poverty alleviation in Africa should consider large-scale, area-wide tsetse control involving all proven methods, including aerial spraying and the sterile insect technique.

Animals↗

PubMed2000

Control of Glossina longipennis (Diptera: Glossinidae) by insecticide-treated targets at Galana ranch, Kenya, and confirmation of the role of G. longipennis as a vector of cattle trypanosomiasis.

Glossina longipennis Corti was studied in Galana Ranch, Kenya over a four year period, in two areas (Tank E and Lali) where the species was abundant and other species were absent or scarce. There was active transmission of trypanosomiasis to cattle in both areas, the parasite species being Trypanosoma vivax Ziemann and T. congolense Broden. Mean infection rates of the G. longipennis were 1.1% and 0. 55% for T. vivax and T. congolense respectively at Tank E, and 0.88% and 0.15% at Lali. Experimental transmission studies showed that cattle in fly-proof enclosures challenged with wild G. longipennis collected from Galana became infected with both trypanosome species. A tsetse control operation in one area (Tank E) using targets impregnated with deltamethrin in an oil formulation reduced the population of G. longipennis by 98% over one year, despite evidence of re-invasion. Populations of G. longipennis in the other area (Lali) were relatively stable over the whole study period. The effect of tsetse control on the incidence of cattle trypanosomiasis at Tank E was less clear than that on tsetse numbers, probably due to the lack of a sustained reduction in tsetse numbers. However, a significant relationship was demonstrated between fortnightly incidence measurements and electric net catches of G. longipennis at Tank E. A further significant predictor of incidence was rainfall in the previous four to seven weeks. This study confirms the importance of G. longipennis as a vector of bovine trypanosomiasis in areas where it is the predominant tsetse present.

Animals↗

PubMed1990

The possible role of Rickettsia-like organisms in trypanosomiasis epidemiology.

A simple model of human and animal trypanosomiasis is proposed in which the Ross equation for disease transmission is supplemented by a differential equation describing the inheritance of susceptibility in the vector. The model predicts an equilibrium state of balanced polymorphism for the fraction, theta, of susceptible tsetse and the occurrence of periodic epidemics at roughly the observed intervals. A loss of infectivity to tsetse of mechanically transmitted strains of trypanosome would seem to be a good evolutionary strategy for the trypanosome. The main implication for disease control is that measures initially reducing trypanosomiasis incidence could trigger off subsequent epidemics. Since theta leads incidence, monitoring theta could give several years advance warning of major epidemics. The model leads to oscillations in prevalence which are only lightly damped. Other mechanisms producing periodic epidemics would interact with this mechanism, and result in only one sequence of recurrent epidemics. With typical random variation of tsetse numbers about the seasonal norm the model shows the behaviour of a narrow-band system excited by broad-band noise, i.e. predicted trypanosomiasis incidence exhibits an undamped series of oscillations of variable amplitude and phase, similar to what is actually observed.

Animals↗

PubMed1993

Monitoring trypanosomiasis in space and time.

The paper examines the possible contributions to be made by Geographic Information Systems (GIS) to studies on human and animal trypanosomiasis in Africa. The epidemiological characteristics of trypanosomiasis are reviewed in the light of the formula for the basic reproductive rate or number of vector-borne diseases. The paper then describes how important biological characteristics of the vectors of trypanosomiasis in West Africa may be monitored using data from the NOAA series of meteorological satellites. This will lead to an understanding of the spatial distribution of both vectors and disease. An alternative, statistical approach to understanding the spatial distribution of tsetse, based on linear discriminant analysis, is illustrated with the example of Glossina morsitans in Zimbabwe, Kenya and Tanzania. In the case of Zimbabwe, a single climatic variable, the maximum of the mean monthly temperature, correctly predicts the pre-rinderpest distribution of tsetse over 82% of the country; additional climatic and vegetation variables do not improve considerably on this figure. In the cases of Kenya and Tanzania, however, another variable, the maximum of the mean monthly Normalized Difference Vegetation Index, is the single most important variable, giving correct predictions over 69% of the area; the other climatic and vegetation variables improve this to 82% overall. Such statistical analyses can guide field work towards the correct biological interpretation of the distributional limits of vectors and may also be used to make predictions about the impact of global change on vector ranges. Examples are given of the areas of Zimbabwe which would become climatically suitable for tsetse given mean temperature increases of 1, 2 and 3 degrees Centigrade. Five possible causes for sleeping sickness outbreaks are given, illustrated by the analysis of field data or from the output of mathematical models. One cause is abiotic (variation in rainfall), three are biotic (variation in vectorial potential, host immunity, or parasite virulence) and one is historical (the impact of explorers, colonizers and dictators). The implications for disease monitoring, in order to anticipate sleeping sickness outbreaks, are briefly discussed. It is concluded that present data are inadequate to distinguish between these hypotheses. The idea that sleeping sickness outbreaks are periodic (i.e. cyclical) is only barely supported by hard data. Hence it is even difficult to conclude whether the major cause of sleeping sickness outbreaks is biotic (which, in model situations, tends to produce cyclical epidemics) or abiotic.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2003

Human African trypanosomiasis: quantitative and qualitative assessment of intrathecal immune response.

Quantitative and qualitative techniques for assessment of the intrathecal humoral immune response in human African trypanosomiasis were compared, and their diagnostic potential for detection of the meningo-encephalitic stage of the disease was evaluated. Total and trypanosome specific immunoglobulin G (IgG) and IgM intrathecal synthesis were studied in paired cerebrospinal fluid (CSF) and blood samples of 38 trypanosomiasis patients and in three controls using Reiber's formulae. The presence of CSF-specific oligoclonal IgG and of trypanosome-specific antibodies was determined using iso-electric focusing followed by immunoblotting and antigen-driven immunoblots. The intrathecal IgG fraction (16% positive) and oligoclonal IgG detection (24% positive) were insensitive for detection of an intrathecal humoral immune response. Trypanosome-specific IgG synthesis, reflected by the IgG antibody index (AI) (26% positive), was confirmed by the presence of oligoclonal specific IgG (47% positive), but the latter was more sensitive. Although the detection technique failed for oligoclonal IgM, the intrathecal IgM fraction (42% positive) and the IgM AI (32% positive) indicated that the meningo-encephalitic stage of the disease is characterized by a dominant intrathecal IgM response, which was higher than the IgG response. The highest combination of diagnostic sensitivity and specificity for the meningo-encephalitic stage of trypanosomiasis was observed for quantitative IgM determinations.

Albumins↗

PubMed1993

Trypanosomiasis of the central nervous system.

American (Chagas' disease) and African (sleeping sickness) trypanosomiasis are diseases that are endemic in parts of Latin American and Africa, respectively. Physicians in developed countries may occasionally see cases because of extensive travel and immigration from endemic countries. In addition, in American trypanosomiasis, transmission via contaminated blood transfusions poses significant risks of causing acute Chagas' disease in immunocompromised patients. Both forms of trypanosomiasis have neurologic manifestations. Chagas' disease can present as acute meningoencephalitis in children and some immunocompromised patients. Additionally, there are increasingly frequent reports of neurologic syndromes, including CNS mass lesions, in HIV-infected patients. African sleeping sickness has prominent CNS pathologic features in stage II disease. Proposed pathogenetic mechanisms and diagnostic and therapeutic considerations are reviewed in this article.

Animals↗

PubMed2003

Intrathecal immune response pattern for improved diagnosis of central nervous system involvement in trypanosomiasis.

Diagnosis of central nervous system (CNS) involvement in human African trypanosomiasis is crucial in determination of therapy. Cerebrospinal fluid (CSF) and serum immunoglobulin concentrations, blood-CSF barrier dysfunction, pattern of intrathecal immunoglobulin synthesis, trypanosome-specific antibody synthesis, and CSF lactate concentrations were analyzed in 272 patients with Trypanosoma brucei gambiense infection. As part of the 2- or 3-class immune response, the predominant intrathecal IgM synthesis was the most sensitive (95%) marker for inflammation of the brain. We propose to replace the World Health Organization (WHO) criteria (white blood cell count >5 cells/microL and presence of trypanosomes in CSF) with a new approach for stage determination in trypanosomiasis: CNS involvement is diagnosed only in patients with >20 cells/microL or with intrathecal IgM synthesis, independent of the presence of trypanosomes in CSF. Compared with the use of these new criteria, the WHO criteria incorrectly classified 49 of 234 patients in the meningoencephalitic stage and 7 of 38 patients in the hemolymphatic disease stage. We also show that trypanosomiasis-related immunoglobulin patterns are of value in differential diagnosis.

Adult↗

PubMed2004

Twenty-four-hour disruption of the sleep-wake cycle and sleep-onset REM-like episodes in a rat model of African trypanosomiasis.

STUDY OBJECTIVES: Patients with human African trypanosomiasis (sleeping sickness) due to the inoculation of Trypanosoma brucei gambiense or rhodesiense show a major disruption of the 24-hour sleep-wake distribution, accompanied by the occurrence of sleep-onset rapid-eye-movement (REM) sleep episodes, proportional to the severity of the illness. Although animal models of human African trypanosomiasis have been developed to understand the pathogenic mechanisms leading to immune alterations, the development of an animal model featuring the alterations of endogenous biologic rhythms remains a necessity. ANIMALS: Sprague-Dawley rats (N = 10) entrained to a 12:12-hour dark-light regimen. INTERVENTIONS: Rats were infected with Trypanosoma brucei brucei AnTat 1.1E and instrumented with electrocorticographic and electromyographic electrodes. Polysomnography was recorded continuously from 2 days before infection until the animal's death. MEASUREMENTS AND RESULTS: The analysis of the spontaneous sleep-wake architecture revealed an increased proportion of slow-wave sleep (SWS) and a decreased amount of wakefulness 2 days before death. Considerable sleep fragmentation was observed in the infected rats, with numerous changes in sleep-wake stages and an increased number of episodes of wakefulness and SWS. Infected rats presented a fragmented pattern of SWS and a marked reduction in the mean paradoxical-sleep (PS) latency, resulting in a considerable disruption of the PS-SWS sequences. Abnormal transitions, particularly the appearance of sleep-onset REM episodes, marked the disruption of the internal sleep structure. The electrocorticogram traces were modified during SWS, with the occurrence of abnormal hypersynchronic slow waves and a disappearance of spindles. CONCLUSION: The Trypanosoma brucei brucei-infected rat is a good model of the syndrome seen in human African trypanosomiasis, ie, the 24-hour disruption of the sleep-wake cycle and the occurrence of sleep-onset REM-like sleep episodes.

Animals↗

PubMed2005

Trypanosomiasis in Kinshasa: distribution of the vector, Glossina fuscipes quanzensis, and risk of transmission in the peri-urban area.

Abstract. Because human and animal cases of African trypanosomiasis have been reported in and around the city of Kinshasa for a long time, the likelihood of local transmission was examined. A georeferenced image of the city was produced, based on a satellite image (SPOT 4). Urban, peri-urban and rural areas were delineated. All recent data on captures of Glossina fuscipes quanzensis Pires (Diptera: Glossinidae) between 1999 and 2004, as well as epidemiological data on a 1999 outbreak of human trypanosomiasis by Trypanosoma brucei gambiense in the Kisenso District, were entered in a geographical information system (GIS). Tsetse flies were mainly found along some of the major rivers in the rural and peri-urban area of Kinshasa. Unsupervised classification of the satellite image allowed identification of riverine habitats suitable for tsetse flies and indicated sites where further entomological surveys were needed. The study produced strong indications that local transmission of human trypanosomiasis had occurred in the recent past in the peri-urban zone of Kinshasa.

Animals↗

PubMed1996

Topical chemotherapy for experimental murine African CNS-trypanosomiasis: the successful use of the arsenical, melarsoprol, combined with the 5-nitroimidazoles, fexinidazole or MK-436.

The 5-nitroimidazoles, MK-436 and fexinidazole dissolved in dimethylsulphoxide can be converted by the addition of hydroxypropylcellulose into gels which facilitates the ease and accuracy of administration. When these gels are used in combination with melarsoprol gel they are capable of curing experimental murine CNS-trypanosomiasis with a one-day treatment. The use of melarsoprol/MK-436 was more efficient than melarsoprol/fexinidazole gels. Thus while a single treatment with 0.1 ml 3.6% melarsoprol gel with 0.1 ml (14.3 mumol) fexinidazole gel cured the infected mice, the same dose of melarsoprol gel with 0.1 ml (4.0 mumol) of MK-436 gel was equally effective. It was also possible to prepare a combined melarsoprol/MK-436 gel which cured experimental CNS-trypanosomiasis with a single treatment. Topical treatment with this melarsoprol/MK-436 gel mixture also resolved clinically the hind leg paralysis which is associated with post-treatment reactive encephalopathy caused by non-curative treatment of CNS-trypanosomiasis.

Administration, Topical↗

PubMed1997

Trypanosomiasis.

African (sleeping sickness) and American (Chagas' disease) trypanosomiasis, caused by protozoa of the family Trypanosomatidae, are diseases that are endemic in parts of Africa and Latin America, respectively. Physicians in developed countries may occasionally see cases because of extensive travel and immigration from endemic countries. Although neurological involvement is common in both, its incidence and clinical presentation differ considerably. African trypanosomiasis, caused by subspecies of Trypanosoma brucei (T b rhodesiense, T b gambiense), is transmitted by the tsetse fly and causes meningoencephalitis, in which somnolence is a prominent feature. Parasites may reach the brain parenchyma through the choroid plexus or the Virchow Robin spaces. American trypanosomiasis, caused by Trypanosoma cruzi is transmitted by reduviid bugs. While lesions in the central nervous system are not prominent, except in the reactivated forms which occur in immunodeficient patients, the peripheral nerve, mainly the autonomic nervous system, is frequently involved, leading to the cardiomegaly and the digestive megaviscera. Congenital infections may also occur. In this paper we give an account of the epidemiology, clinical presentation and pathological features of these two protozoal infections based on human and experimental studies of both the central and peripheral nervous system.

Animals↗

PubMed2006

Diagnosing human African trypanosomiasis in Angola using a card agglutination test: observational study of active and passive case finding strategies.

OBJECTIVE: To assess the operational feasibility of detecting human African trypanosomiasis by active and passive case finding using the card agglutination test with serial dilution of serum to guide treatment. SETTING: Trypanosomiasis control programme in the Negage focus, northern Angola, during a period of civil war. DESIGN: Observational study. PARTICIPANTS: 359 patients presenting themselves to health centres with symptoms (passive case finding) and 14,446 people actively screened in villages. MAIN OUTCOME MEASURES: Whole blood and serological tests at different dilutions using the card agglutination test, and detection of parasites by microscopy. RESULTS: Active case finding identified 251 people with a positive card agglutination test result, 10 of whom had confirmed parasites. In those presenting for investigation 34 of 51 with a positive card agglutination test result at the dilution of 1:8 or more used to guide treatment had parasites in blood, lymph node fluid, or cerebrospinal fluid, compared with 10 of 76 in those detected by active case finding: positive predictive values of 67% for passive case detection and 13% for active case detection. Only at a cut-off dilution more than 1:32 was the positive predictive value in active case detection reasonable (46%) and at this dilution 40% of microscopically proved cases were missed. CONCLUSIONS: The card agglutination test is useful for initial screening in active detection of cases with human African trypanosomiasis but, given the toxicity of the drugs, serology using the card agglutination test should be not used alone to guide treatment after active case finding. A second confirmatory test is needed.

Adolescent↗

PubMed1976

Pancarditis affecting the conducting system and all valves in human African trypanosomiasis.

This paper describes the pathological features of 10 cases of human African trypanosomiasis occurring in Uganda over an 8-year period. Three cases were clinically proved, and in all 10 cases chronic meningoencephalitis and myocarditis were present. There was chronic pancarditis in 6 cases, and in 3 of these there was a generalized focal valvulitis and in 2 lesions of the conducting system. Previous descriptions of carditis in human African trypanosomiasis are briefly reviewed, and the present findings are compared with some cardiomyopathies as well as American human and experimental trypanosomiasis.

Adolescent↗