Human african trypanosomiasis: current standing and challenges

Human African trypanosomiasis (HAT) caused by the protozoan Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, and transmitted by the tsetse fly (genus Glossina), affects 36 Sub-Saharan African countries with considerable public health impact. Despite approximately 15,000 infected individuals and 70 million at risk, in recent years the World Health Organization has mentioned removal of HAT from the list of Neglected Tropical Diseases by 2020, due to the decrease in cases over the last two decades. When untreated, the disease presents high lethality rates and the available treatments are complicated to administer, highly toxic, and do not guarantee cure, especially in the advanced stages of the disease. Further, there is no prospect for vaccine development in the near future. The present review compiles information on the history of the clinical aspects of HAT, as well as its epidemiology, diagnosis, therapy, and prophylaxis, as well as updating information on the current panorama and perspectives regarding the disease.

Relationship between Neutrophil-To-Lymphocyte Ratio and Electrocardiographic Ischemia Grade in STEMI / Associação entre a Relação Neutrófilos/Linfócitos e o Grau de Isquemia Eletrocardiográfica no IAMEST

Background: Neutrophil-to-lymphocyte ratio (NLR) has been found to be a good predictor of future adverse cardiovascular outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Changes in the QRS terminal portion have also been associated with adverse outcomes following STEMI. Objective: To investigate the relationship between ECG ischemia grade and NLR in patients presenting with STEMI, in order to determine additional conventional risk factors for early risk stratification. Methods: Patients with STEMI were investigated. The grade of ischemia was analyzed from the ECG performed on admission. White blood cells and subtypes were measured as part of the automated complete blood count (CBC) analysis. Patients were classified into two groups according to the ischemia grade presented on the admission ECG, as grade 2 ischemia (G2I) and grade 3 ischemia (G3I). Results: Patients with G3I had significantly lower mean left ventricular ejection fraction than those in G2I (44.58 ± 7.23 vs. 48.44 ± 7.61, p = 0.001). As expected, in-hospital mortality rate increased proportionally with the increase in ischemia grade (p = 0.036). There were significant differences in percentage of lymphocytes (p = 0.010) and percentage of neutrophils (p = 0.004), and therefore, NLR was significantly different between G2I and G3I patients (p < 0.001). Multivariate logistic regression analysis revealed that only NLR was the independent variable with a significant effect on ECG ischemia grade (odds ratio = 1.254, 95% confidence interval 1.120–1.403, p < 0.001). Conclusion: We found an association between G3I and elevated NLR in patients with STEMI. We believe that such an association might provide an additional prognostic value for risk stratification in patients with STEMI when combined with standardized risk scores. .

Fundamento: A relação neutrófilos/linfócitos (N/L) tem sido descrita como boa preditora de eventos cardiovasculares adversos futuros em pacientes com infarto agudo do miocárdio com elevação do segmento ST (IAMEST). Mudanças na porção terminal do complexo QRS também têm sido associadas a eventos adversos após IAMEST. Objetivo: Investigar a associação entre o grau de isquemia no ECG e a relação N/L em pacientes com IAMEST para determinar fatores de risco convencionais adicionais na estratificação precoce de risco. Métodos: Pacientes com IAMEST foram investigados. O grau de isquemia foi analisado a partir do ECG obtido à admissão. A contagem de leucócitos e seus subtipos foi realizada a partir de hemograma automatizado. De acordo com o grau de isquemia presente no ECG de admissão, os pacientes foram classificados em dois grupos, isquemia grau 2 (IG2) e isquemia grau 3 (IG3). Resultados: Pacientes com IG3 apresentaram valores médios significativamente menores de fração de ejeção do ventrículo esquerdo do que os pacientes com IG2 (44,58 ± 7,23 versus 48,44 ± 7,61; p = 0,001). Como esperado, a taxa de mortalidade intra-hospitalar aumentou proporcionalmente com o aumento no grau de isquemia (p = 0,036). Houve diferenças significativas nas porcentagens de linfócitos (p = 0,010) e de neutrófilos (p = 0,004) e, portanto, a relação N/L diferiu significativamente entre pacientes com IG2 e IG3 (p < 0,001). À análise de regressão logística multivariada, apenas a relação N/L emergiu como variável independente com efeito significativo sobre o grau de isquemia no ECG (odds ratio = 1,254; intervalo de confiança de 95% 1,120-1,403; p < 0,001). Conclusão: Nós encontramos uma associação entre IG3 e relação N/L aumentada em pacientes com IAMEST. Acreditamos que esta associação possa oferecer um valor prognóstico adicional para estratificação de risco em pacientes com IAMEST quando usado em combinação com escores de risco padronizados. .

Anti-trypanosomal Activity of Potential Inhibitors of Trypanosoma brucei Glycolytic Pathway Enzymes Selected by Docking Studies

Human African trypanosomiasis (HAT); a potentially fatal protozoan infection caused by tsetse-fl mediated transmission of Trypanosoma brucei (T. Brucei); is largely recognized as a neglected disease. The repertoire of drugs that is effective against the infection is limited and all drugs have several drawbacks including high level of toxicity; difficult administration regimens; and the resurgence of resistance. At present the biology of the parasite is well studied and a number of technologies are now available which can aid in the identifiation of potential drug targets. This review identifis putative inhibitors of trypanosomal glycolytic enzymes

Modelling the Use of Insecticide-Treated Cattle to Control Tsetse and Trypanosoma brucei rhodesiense in a Multi-host Population

T. b. rhodesiense is the acute form of African human trypanosomiasis or sleeping sickness which is common in East and Southern Africa. Trypanosomiasis is caused by the parasite Trypanosoma brucei and transmitted by tsetse flies (genus Glossina spp). Treatment of livestock in sub-Saharan Africa with trypanocidal drugs has been hindered by drug resistance and proves to be too expensive for many farmers. Tsetse control methods include aerial and ground spraying; sterile insect technique; and bait technology; including the use of insecticide-treated cattle (ITC). We compared two techniques of application of insecticides on cattle using a mathematical model: whole-body (WB); where insecticides are applied on the entire animals body and restricted application (RAP); where insecticides are applied on the legs; belly and ears of the animal

Transmission of Human African Trypanosomiasis in the Komo-Mondah focus; Gabon

Knowledge about transmission of sleeping sickness in a given focus is of a great importance since it governs the efficacy and the cost-effectiveness of control strategy. The Komo-Mondah focus is the most endemic sleeping sickness focus of Gabon. This focus has hardly been investigated and available publications are more than thirty years old. In order to update transmission features of sleeping sickness in that focus; we have conducted epidemiological and entomological surveys in March-April 2008. Methods: Epidemiological investigation relied on a case-control study using a quantitative and qualitative methodology (a structured questionnaire). Cases were affected people (parasitological positive) diagnosed by the national control program from 2004 to 2007; controls were those found disease-free after clinical examination and biological tests in the same period. They were asked to respond to a standard questionnaire concerning their activities after having signed a written consent. An unvaried analysis was first performed and then a multivariate analysis using the conditional logistic regression for matching method. Traps were then set out for four days in areas where people were working. Tsetse flies captured were identified and dissected; their density and human-fly contact points were determined. Results: A risk of infection was associated with fishing activities (Odds-ratio: 5.69; CI95: 3.38-9.57). Three species of Glossina were captured: Glossina palpalis palpalis; Glossina fuscipes fuscipes and G. Caliginea. Human-fly contact points were mainly landing stages. Conclusion: A combined strategy of case-detection and vector control targeted at landing stages should be efficient against the disease

Effets de la pression demographique sur la repartition des glossines et l`evolution de la trypanosomiase humaine africaine en milieu urbain et periurbain de la ville province de Kinshasa; Republique Democratique du Congo

En 1999; les points de contact homme-glossines et leurs relations avec la persistance de la trypanosomiase humaine africaine dans l`espace urbain et periurbain de la ville province de Kinshasa ont ete etablis. Un suivi de l`evolution de la maladie et de la presence des glossines par rapport aux activites des populations de la ville de Kinshasa montre qu`apres 7ans; les espaces de Djili; Kimbanseke et Buma ont ete debarrasses des glossines et que le taux de prevalence de la trypanosomiase humaine africaine dans ces zones a diminue de maniere significative. L`anthropisation de ces espaces a eu un impact sur la distribution des glossines et de la maladie. En revanche; au niveau de Kimwenza et de Djili brasserie; deux quartiers de la peripherie de la ville; la reduction de l`espace occupe par les glossines a plutot augmente le contact homme mouche tse-tse avec comme consequence l`augmentation du risque de la transmission de la maladie du sommeil

La trypanosomiase humaine africaine en Afrique centrale en 2007: progres et contraintes

L`Afrique centrale est une region historique de la trypanosomiase humaine africaine. A l`aube du vingt et unieme siecle; la maladie reste epidemique en Angola et en Republique Democratique du Congo et preoccupante dans les autres pays de la region. Malgre la mise en ouvre de nombreux efforts de lutte; le seuil de l`elimination fixe a 1 cas par an pour 10.000 habitants exposes est encore loin d`etre atteint. La transmission se poursuit dans les foyers a faible niveau d`endemicite du fait de l`absence de lutte antivectorielle ciblee au point de contact homme-glossines. Des cas d`echecs therapeutiques sont observes dans certains foyers. De plus en plus; des foyers quiescents se remettent en activite. Une strategie de lutte associant le depistage-traitement des malades et la lutte antivectorielle permettrait d`atteindre plus rapidement l`objectif de l`elimination de la maladie dans les foyers. La presence d`un personnel qualifie et equipe permettrait d`assurer une surveillance sentinelle dans les foyers

Factors Influencing Individual and Community Participation in the Control of Tetse Flies and Human African Trypanosomiasis in Urambo District; Tanzania

This study was carried out to assess the knowledge and level of individual and community participation in the control of Human African trypanosomiasis in Urambo District; western Tanzania. Semi structured questionnaires were used to collect information from individuals at house hold level. Retrospective data of HAT was sought from the medicalofficers in-charge of health facilities. The results indicate that; 191 (90.5 ; n = 211) individuals knew tsetse flies and 187(88.6; n=211) knew HAT. All nine key informants reported that; the communities were aware of HAT while seven key informants reported that; the communities were aware of health risks associated with tsetse bites in human. There was poor knowledge about the role played by animals in the transmission of HAT (26.7; n=187). Majority of those who knew HAT (n = 187) were willing to contribute labour (70.1) and money (64.2) to tsetse and HAT control whereas amongst those who knew tsetse flies; 66.5 and 60.7 were willing to contribute labour and money; respectively. Amongst those who knew any HAT control technique (n = 108); 78.7 and 82.4were willing to contribute money and labour respectively. A total of 454 cases of HAT were reported in the area from 1999 to 2006. It is concluded that; the factors influencing individual and community participation include the knowledge of tsetse; HAT and control measures

The effects of a DNA virus infection on the reproductive potential of female tsetse flies, Glossina morsitans centralis and Glossina morsitans morsitans (Diptera: Glossinidae)

Reproductive anomalies associated with the tsetse DNA virus infection in the female tsetse hosts, Glossina morsitans centralis Machado and Glossina morsitans morsitans Westwood, inoculated with the virus during the 3rd instar larval stage were studied and the data compared to those obtained from the control females injected with sterile physiological saline. Virus infected flies had significantly longer first and second pregnancy cycles (P<0.0001) and produced pupae that were of significantly less weight in miligrams (P<0.0001) compared to controls. Transmission of the virus to progeny was not absolute and only 21 per cent of G.m. centralis and 48 per cent of G.m. morsitans first progeny flies from infected females developed salivary gland hypertrophy as a result of transmission from mother to progeny. The virus infected females produced significantly fewere pupae compared to the controls during the experimental period (P<0.00001).

The daily activity pattern and feeding habits of glossina longipenis cort (diptera; glossinidie) at Galana Ranch; South-Eastern Kenya

Sampling of Glossina lognipennis Corti for 24 hours using baited F-3 traps; mobile and stationary electric screens; stationary ox and ox-fly round showed two main activity peaks at dawn and dusk. The evening peak was more pronounced than the morning one. Very little activity was recorded during the rest of the day. An incompete ring of electric screens arranged round a cattle enclosure showed that G. longipennis is attracted to; and feeds on cattle; especially during peak activity times with a feeeding success of about 7. The number of flies caught on the outside and inside of the elctric screens was significantly different at the 5 level. Analysis of blood meal samples from fed flies indicated a wide diversity of host for G. longipennis with a preference to suids. Over 65 of the total identified blood meal samples were from suids of which 60 alone were from bushpig; while bovines other than buffalo; collected in an area where cattle are kept; provided only 7 of the feeds

The economics of trypanotolerance on Galana Ranch

Trials on the control of animal trypanosomiasis have been undertaken on Galana Ranch for more than ten years; and the results have been presented in many arenas concentrating primarily on productivity and genetic aspects. There has not yet; however; been a comprehensive economic analysis of these trials. This paper address the issue of the relative profitability of using trypanotolerant orma cattle compared with faster-growing but more susceptivle improved Kenya Boran. The results of eight different trails; mostly of twelve months duration; carried out in two areas of Galana Ranch; Kilifi District; with varying trypanosomiasis challenge between 1981-1989; are presented here. All trails compare the performance of groups of Orma and improved Boran steers; in terms of weight gain and the cost of tsetse/trypanosomiasis control required to achieve those rates of growth. Five of the trials compared alternative drug regimes for trypanosomiasis control; and three involved tsetse fly control using insecticide-impregnated targets. In trails using trypanocides; the important determinant of relative profitability is the trade-off between weight gain and treatment cost; although there is variation between years; especially with Orma cattle. In those trials where the Galana weight gains are significantly higher than Orma; the extra income compensates for increased treatment expenditure. However; in those cases where there is no major weight gain difference; the requirement of the Orma for less drug treatments makes it the more profitable breed. Where targets have been the major control measure; costs are similar for the Galana and Orma animals that weight gain is therefore the major determinant of relative profitability

Animal productivity in tsetse-infested area of South West Kenya

Since 1990; a baseline survey of cattle productivity has been carried out on the Olkiramatina Group Ranch; Kajiado District. The aim of this survey was to assess the impact of seasonally high tsetse challenge and the resulting trypanosome infections. Management strategies among the pastoralist farmers and the effects of traditional and introduced tsetse and trypanosomiasis control regimes were also assessed. Two traditionally managed herds (A and B) were monitored by monthly weighing and sampling for trypanosomiasis. Milk off take was recorded every two weeks and herd compositon and dynamics monitored weekly. The major constraint to productivity during the first year of the study was prolonged drought affecting traditional transhumance grazing practices. The trypanosomiasis incidence rate of a control herd was consistently higher than the trypanosomiasis prevelance rate in the survey herds. There was an increase in disease prevalence at the end of along dry season and during the short rain season. Mortality rates at this time also increased. During the period; two calving seasons were recorded; during May to June 1991 and between December 1990 and February 1991. Herd A recorded a 73.5 calving rate between November 1990 and November 1991; compared with 52 in Herd B. Differences in cattle grazing management and drug treatments between herds were recorded. Cattle performance was characterised by a large drop in the body weight of mature animals after calving; long periods of return to service and low calf growth rates. This study is on-going

Description of a mono-screen trap for Glossina fuscipes Newstead in Uganda

A low-cost mono-screen trap for Glossina fuscipes suitable for use by a rural community in Uganda is describe. The trap has a single blue/black screen and a cone made from mosquito netting. The supporting frame work is made from indigenous plant materials. The differences in trap catches between the mono-screen; biconical; pyramidal and traps were highly significant (P less than 0.001. Taking the standard biconical trap as control; the mono-screen trap was 1.25 times as efficient and the pyramidal trap was 0.04 times as efficient. The cost of one mono-screen trap is estimated as 1800 Uganda shillings (=U.S. $4.7); about half the cost of a pyramidal trap and one-quarter the cost of a biconical trap. The prospects for the use of the mono-screen trap by the community are discussed

The status of the tsetse fly as the vector of human trypanosomiasis in Malawi

A report on the activities of the Regional Tsetse and Trypanosomiasis Control Programme and results of a national survey of the primary and seconadry foci

East African Trypanosomiasis in Nkhotakota District

A marked increase in trypanosomiasis has been seen at Nkhotakota District Hospital since September 1989. This report presents background information; the extent of the recent outbreak and suggested revised treatment protocol. Suggestions are made for preventative measures against the spread of trypanosomiasis

Sleeping sickness surveys: game reserve adjacent to villages in Malawi

Although tsetse control measures were discontinued in Malawi in the early 1950s; the prevalence of sleeping sickness apparently remained at low levels. A sleeping sickness survey conducted in 1987 to 1989 revealed a prevalence of the disease of 3 percent (103/3000). Seven percent (215/3000) of the individuals tested were positive for malaria. 87 individuals traced 2 years after hospital discharge were found well and active in their villages. Four died in villages after hospital treatment. Three relapsed and were readmitted to hospital. Sera from 160 game ranger volunteers and from 82 suspected cases of Rhodesian sleeping sickness were tested by use of ELISA; IFAT and CATT. ELISA and CATT; though not specific; proved to be useful tests for mass screening for human trypanosomiasis. Thick blood smear was found to be the best diagnostic method in this survey