infection by protozoan hemo- flagellates of the Trypanosoma brucei complex, 2 subspe- cies of which cause disease in humans: Trypanosoma bru- cei gambiense...public release; distribution unlimited 13. SUPPLEMENTARY NOTES See also ADA545141. Chapter 3 from e-book, Topics on the Pathology of Protozoan and...the brief ferry crossing. 2 3 • Topics on The paThology of proTozoan and invasive arThropod diseases Three severe epidemics of African trypanosomiasis
Lejon, Veerle; Bentivoglio, Marina; Franco, José Ramon
Human African trypanosomiasis or sleeping sickness is a neglected tropical disease that affects populations in sub-Saharan Africa. The disease is caused by infection with the gambiense and rhodesiense subspecies of the extracellular parasite Trypanosoma brucei, and is transmitted to humans by bites of infected tsetse flies. The disease evolves in two stages, the hemolymphatic and meningoencephalitic stages, the latter being defined by central nervous system infection after trypanosomal traversal of the blood-brain barrier. African trypanosomiasis, which leads to severe neuroinflammation, is fatal without treatment, but the available drugs are toxic and complicated to administer. The choice of medication is determined by the infecting parasite subspecies and disease stage. Clinical features include a constellation of nonspecific symptoms and signs with evolving neurological and psychiatric alterations and characteristic sleep-wake disturbances. Because of the clinical profile variability and insidiously progressive central nervous system involvement, disease staging is currently based on cerebrospinal fluid examination, which is usually performed after the finding of trypanosomes in blood or other body fluids. No vaccine being available, control of human African trypanosomiasis relies on diagnosis and treatment of infected patients, assisted by vector control. Better diagnostic tools and safer, easy to use drugs are needed to facilitate elimination of the disease.
Berrang-Ford, Lea; Lundine, Jamie; Breau, Sebastien
Human African Trypanosomiasis (HAT) has reemerged in sub-Saharan Africa as a disease of major public health importance. The success of HAT elimination in sub-Saharan Africa is subject to the feasibility of controlling, eliminating, or mitigating the determinants of incidence in affected countries. Conflict has been widely recognized and cited as a contributing factor to the resurgence of HAT in many countries, as well as to continuing HAT incidence in politically unstable and resource-poor regions. Despite extensive anecdotal and qualitative recognition of the role of conflict, there has been no quantitative research of this topic at the population level in affected African countries. We characterize the qualitative and quantitative associations between HAT incidence and conflict-related processes in HAT-affected African countries over the past 30 years. HAT and conflict-related data were collected for 35 affected countries in sub-Saharan Africa for the years 1976-2004. Descriptive and univariate inferential statistics, as well as negative binomial regression modeling, are used to assess the associations between HAT and conflict. A space-time scan statistic is used to identify significant incidence clusters. Clusters of HAT incidence over the past 30 years have predominantly coincided with periods of conflict or socio-political instability. HAT cases occurred significantly more often in countries and during years with conflict, high political terror, and internationalized civil war. The results indicate a lag period between the start of conflict events and a peak in incidence of approximately 10 years. We recommend explicit consideration and quantification of socio-political measures such as conflict and terror indices in GIS (Geographic Information Systems)-based risk assessments for HAT policy and intervention.
Franco, Jose R; Simarro, Pere P; Diarra, Abdoulaye; Jannin, Jean G
Human African trypanosomiasis (HAT), or sleeping sickness, is caused by Trypanosoma brucei gambiense, which is a chronic form of the disease present in western and central Africa, and by Trypanosoma brucei rhodesiense, which is an acute disease located in eastern and southern Africa. The rhodesiense form is a zoonosis, with the occasional infection of humans, but in the gambiense form, the human being is regarded as the main reservoir that plays a key role in the transmission cycle of the disease. The gambiense form currently assumes that 98% of the cases are declared; the Democratic Republic of the Congo is the most affected country, with more than 75% of the gambiense cases declared. The epidemiology of the disease is mediated by the interaction of the parasite (trypanosome) with the vectors (tsetse flies), as well as with the human and animal hosts within a particular environment. Related to these interactions, the disease is confined in spatially limited areas called “foci”, which are located in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT is, therefore, determined by the possibility of contact of a human being with an infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th century; intensive activities have been set up to confront the disease, and it was under control in the 1960s, with fewer than 5,000 cases reported in the whole continent. The disease resurged at the end of the 1990s, but renewed efforts from endemic countries, cooperation agencies, and nongovernmental organizations led by the World Health Organization succeeded to raise awareness and resources, while reinforcing national programs, reversing the trend of the cases reported, and bringing the disease under control again. In this context, sustainable elimination of the gambiense HAT, defined as the interruption of the transmission of the disease, was considered as a feasible target for 2030. Since rhodesiense HAT is a zoonosis
Burchmore, Richard J S; Ogbunude, Patrick O J; Enanga, Bertin; Barrett, Michael P
Human African trypanosomiasis or sleeping sickness is resurgent [1,2]. The disease is caused by subspecies of the parasitic haemoflagellate, Trypanosoma brucei. Infection starts with the bite of an infected tsetse fly (Glossina spp.). Parasites move from the site of infection to the draining lymphatic vessels and blood stream. The parasites proliferate within the bloodstream and later invade other tissues including the central nervous system. Once they have established themselves within the CNS, a progressive breakdown of neurological function accompanies the disease. Coma precedes death during this late phase. Two forms of the disease are recognised, one caused by Trypanosoma brucei rhodesiense, endemic in Eastern and Southern Africa, in which parasites rapidly invade the CNS causing death within weeks if untreated. T. b. gambiense, originally described in West Africa, but also widespread in Central Africa, proliferates more slowly and can take several years before establishing a CNS-involved infection. Many countries are in the midst of epidemics caused by gambiense-type parasites. Four drugs have been licensed to treat the disease ; two of them, pentamidine and suramin, are used prior to CNS involvement. The arsenic-based drug, melarsoprol is used once parasites are established in the CNS. The fourth, eflornithine, is effective against late stage disease caused by T. b. gambiense, but is ineffective against T. b. rhodesiense. Another drug, nifurtimox is licensed for South American trypanosomiasis but also been used in trials against melarsoprol-refractory late sage disease. This review focuses on what is known about modes of action of current drugs and discusses targets for future drug development.
Jones, Amy J; Avery, Vicky M
Over the past 17 years, the number of reported cases of human African trypanosomiasis (HAT) has declined by over 90%, a significant result since the disease was highlighted as a public health problem by the WHO in 1995. However, if the goal of eliminating HAT by 2020 is to be achieved, then new treatments need to be identified and developed. A plethora of compound collections has been screened against Trypanosoma brucei spp, the etiological agents of HAT, resulting in three compounds progressing to clinical development. However, due to the high attrition rates in drug discovery, it is essential that research continues to identify novel molecules. Failure to do so, will result in the absence of molecules in the pipeline to fall back on should the current clinical trials be unsuccessful. This could seriously compromise control efforts to date, resulting in a resurgence in the number of HAT cases.
Delespaux, Vincent; de Koning, Harry P
Despite the many decades of use of most of the current trypanocides, we know little of their mode of action. This may in part be because most of these will act on multiple targets once inside the cell, and they derive their selective action on the parasite from selective accumulation by the pathogen. Loss of this capacity for drug uptake by the trypanosome would thus be a major cause for drug resistance. We here discuss the use of current drugs against human and veterinary African trypanosomiasis, the prevalence, causes and mechanisms of drug resistance and new developments in trypanosomiasis therapy such as the introduction of nifurtimox and DB289.
Barrett, Michael P; Vincent, Isabel M; Burchmore, Richard J S; Kazibwe, Anne J N; Matovu, Enock
Human African trypanosomiasis or 'sleeping sickness' is a neglected tropical disease caused by the parasite Trypanosoma brucei. A decade of intense international cooperation has brought the incidence to fewer than 10,000 reported cases per annum with anti-trypanosomal drugs, particularly against stage 2 disease where the CNS is involved, being central to control. Treatment failures with melarsoprol started to appear in the 1990s and their incidence has risen sharply in many foci. Loss of plasma membrane transporters involved in drug uptake, particularly the P2 aminopurine transporter and also a transporter termed the high affinity pentamidine transporter, relate to melarsoprol resistance selected in the laboratory. The same two transporters are also responsible for the uptake of the stage 1 drug pentamidine and, to varying extents, other diamidines. However, reports of treatment failures with pentamidine have been rare from the field. Eflornithine (difluoromethylornithine) has replaced melarsoprol as first-line treatment in many regions. However, a need for protracted and complicated drug dosing regimens slowed widespread implementation of eflornithine monotherapy. A combination of eflornithine with nifurtimox substantially decreases the required dose and duration of eflornithine administration and this nifurtimox-eflornithine combination therapy has enjoyed rapid implementation. Unfortunately, selection of resistance to eflornithine in the laboratory is relatively easy (through loss of an amino acid transporter believed to be involved in its uptake), as is selection of resistance to nifurtimox. The first anecdotal reports of treatment failures with eflornithine monotherapy are emerging from some foci. The possibility that parasites resistant to melarsoprol on the one hand, and eflornithine on the other, are present in the field indicates that genes capable of conferring drug resistance to both drugs are in circulation. If new drugs, that act in ways that will not
Introduction Trypanosoma brucei rhodesiense typically causes acute and severe human African trypanosomiasis in Zambia and other countries in Eastern and Southern Africa. Although a few atypical cases of chronic and mild forms of this disease were reported in Zambia more than 40 years ago, no such cases have been diagnosed over the last four decades. Case presentations For the first case, a 19-year-old Black African woman from the Eastern Province of Zambia presented with symptoms and signs of an atypical chronic and mild form of the disease for a period of 2 years. For the second case, a 16-year-old Black African boy from the Northern Province presented with symptoms and signs of a typical acute and severe form of the disease for 3 weeks. Conclusion Two strains of T. b. rhodesiense with varying degrees of virulence still do exist in Zambia. This has implications for control strategies at the national level. PMID:24529084
Trypanosomes have been recognised as human pathogens for over a century. Human African trypanosomiasis is endemic in an area sustaining 60 million people and is fatal without chemotherapeutic intervention. Available trypanocidal drugs require parenteral administration and are associated with adverse reactions including the development of a severe post-treatment reactive encephalopathy (PTRE). Following infection the parasites proliferate in the systemic compartment before invading the CNS where a cascade of events results in neuroinflammation. This review summarises the clinical manifestations of the infection and chemotherapeutic regimens as well as the current research findings and hypotheses regarding the neuropathogenesis of the disease.
In the 1960s, it appeared that human African trypanosomiasis (HAT) could be effectively controlled, but by the beginning of the twenty-first century several decades of neglect had led to alarming numbers of reported new cases, with an estimated 300 000 people infected. The World Health Organization (WHO) responded with a series of initiatives aimed at bringing HAT under control again. Since 2001, the pharmaceutical companies that produce drugs for HAT have committed themselves to providing them free of charge to WHO for distribution for the treatment of patients. In addition, funds have been provided to WHO to support national sleeping sickness control programmes to boost control and surveillance of the disease. That, coupled with bilateral cooperation and the work of nongovernmental organizations, helped reverse the upward trend in HAT prevalence. By 2012, the number of reported cases was fewer than 8000. This success in bringing HAT under control led to its inclusion in the WHO Roadmap for eradication, elimination and control of neglected tropical diseases, with a target set to eliminate the disease as a public health problem by 2020. A further target has been set, by countries in which HAT is endemic, to eliminate gambiense HAT by reducing the incidence of infection to zero in a defined geographical area. This report provides information about new diagnostic approaches, new therapeutic regimens and better understanding of the distribution of the disease with high-quality mapping. The roles of human and animal reservoirs and the tsetse fly vectors that transmit the parasites are emphasized. The new information has formed the basis for an integrated strategy with which it is hoped that elimination of gambiense HAT will be achieved. The report also contains recommendations on the approaches that will lead to elimination of the disease.
Cecchi, Giuliano; Paone, Massimo; Franco, José R; Fèvre, Eric M; Diarra, Abdoulaye; Ruiz, José A; Mattioli, Raffaele C; Simarro, Pere P
Background Updated, accurate and comprehensive information on the distribution of human African trypanosomiasis (HAT), also known as sleeping sickness, is critically important to plan and monitor control activities. We describe input data, methodology, preliminary results and future prospects of the HAT Atlas initiative, which will allow major improvements in the understanding of the spatial distribution of the disease. Methods Up-to-date as well as historical data collected by national sleeping sickness control programmes, non-governmental organizations and research institutes have been collated over many years by the HAT Control and Surveillance Programme of the World Health Organization. This body of information, unpublished for the most part, is now being screened, harmonized, and analysed by means of database management systems and geographical information systems (GIS). The number of new HAT cases and the number of people screened within a defined geographical entity were chosen as the key variables to map disease distribution in sub-Saharan Africa. Results At the time of writing, over 600 epidemiological reports and files from seventeen countries were collated and included in the data repository. The reports contain information on approximately 20,000 HAT cases, associated to over 7,000 different geographical entities. The oldest epidemiological records considered so far date back to 1985, the most recent having been gathered in 2008. Data from Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea and Gabon from the year 2000 onwards were fully processed and the preliminary regional map of HAT distribution is presented. Conclusion The use of GIS tools and geo-referenced, village-level epidemiological data allow the production of maps that substantially improve on the spatial quality of previous cartographic products of similar scope. The significant differences between our preliminary outputs and earlier maps of HAT transmission areas
Medlock, Jan; Atkins, Katherine E; Thomas, David N; Aksoy, Serap; Galvani, Alison P
Genetic-modification strategies are currently being developed to reduce the transmission of vector-borne diseases, including African trypanosomiasis. For tsetse, the vector of African trypanosomiasis, a paratransgenic strategy is being considered: this approach involves modification of the commensal symbiotic bacteria Sodalis to express trypanosome-resistance-conferring products. Modified Sodalis can then be driven into the tsetse population by cytoplasmic incompatibility (CI) from Wolbachia bacteria. To evaluate the effectiveness of this paratransgenic strategy in controlling African trypanosomiasis, we developed a three-species mathematical model of trypanosomiasis transmission among tsetse, humans, and animal reservoir hosts. Using empirical estimates of CI parameters, we found that paratransgenic tsetse have the potential to eliminate trypanosomiasis, provided that any extra mortality caused by Wolbachia colonization is low, that the paratransgene is effective at protecting against trypanosome transmission, and that the target tsetse species comprises a large majority of the tsetse population in the release location.
AD-A139 365 STUDS OF AFRICAN TRYPANOSOMIASIS AND LEISHMANIASIS(U) f/f ARMY MEDICAL RESEARCH UNITKENYA Apo NEW YORK 09675 M J REARDON ET AL DEC 83...STUDY OF AFRICAN TRYPANOSOMIASIS AND LEISHMANIASIS FINAL REPORT CID LTC M.J. Reardon, VC I.E. Muriithi LTC J.D. Chulay, MC LTC L.D. Hendricks, MSC ym 4...CATALOG NUMBER 4. TITLE (and Subtitle) 5. TYPE OF REPORT & PERIOD COVERED STUDY OF AFRICAN TRYPANOSOMIASIS AND FINAL--October 1982- LEISHMAIASIS 14
Fèvre, Eric M.; Wissmann, Beatrix v.; Welburn, Susan C.; Lutumba, Pascal
Human African trypanosomiasis (HAT, or sleeping sickness) is a protozoan parasitic infection caused by Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense. These are neglected tropical diseases, and T.b. rhodesiense HAT is a zoonosis. We review current knowledge on the burden of HAT in sub-Saharan Africa, with an emphasis on the disability-adjusted life year (DALY), data sources, and methodological issues relating to the use of this metric for assessing the burden of this disease. We highlight areas where data are lacking to properly quantify the impact of these diseases, mainly relating to quantifying under-reporting and disability associated with infection, and challenge the HAT research community to tackle the neglect in data gathering to enable better evidence-based assessments of burden using DALYs or other appropriate measures. PMID:19104653
Rock, Kat S; Stone, Chris M; Hastings, Ian M; Keeling, Matt J; Torr, Steve J; Chitnis, Nakul
Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is usually fatal if untreated and transmission occurs in foci across sub-Saharan Africa. Mathematical modelling of HAT began in the 1980s with extensions of the Ross-Macdonald malaria model and has since consisted, with a few exceptions, of similar deterministic compartmental models. These models have captured the main features of HAT epidemiology and provided insight on the effectiveness of the two main control interventions (treatment of humans and tsetse fly control) in eliminating transmission. However, most existing models have overestimated prevalence of infection and ignored transient dynamics. There is a need for properly validated models, evolving with improved data collection, that can provide quantitative predictions to help guide control and elimination strategies for HAT.
Cailliez, M; Poupin, F; Pages, J P; Savel, J
The estimation of blood orosomucoid, haptoglobin, C-reactive protein and immunoglobulins levels, has enable us to prove a specific proteic profile in the human african trypanosomiasis, as compared with other that of parasitic diseases, and with an healthy african reference group. Data processing informatique by principal components analysis, provide a valuable pool for epidemiological surveys.
Kennedy, Peter Ge
Human African trypanosomiasis, or sleeping sickness, is caused by infection with parasites of the genus Trypanosoma, transmitted by the tsetse fly. The disease has two forms, Trypanosoma brucei (T b) rhodesiense and T b gambiense; and is almost always fatal if untreated. Despite a recent reduction in the number of reported cases, patients with African trypanosomiasis continue to present major challenges to clinicians. Because treatment for CNS-stage disease can be very toxic, diagnostic staging to distinguish early-stage from late-stage disease when the CNS in invaded is crucial but remains problematic. Melarsoprol is the only available treatment for late-stage T b rhodesiense infection, but can be lethal to 5% of patients owing to post-treatment reactive encephalopathy. Eflornithine combined with nifurtimox is the first-line treatment for late-stage T b gambiense. New drugs are in the pipeline for treatment of CNS human African trypanosomiasis, giving rise to cautious optimism.
Magez, Stefan; Radwanska, Magdalena
African trypanosomiasis causes devastating effects on human populations and livestock herds in large parts of sub-Saharan Africa. Control of the disease is hampered by the lack of any efficient vaccination results in a field setting, and the severe side effects of current drug therapies. In addition, with the exception of Trypanosoma brucei gambiense infections, the diagnosis of trypanosomiasis has to rely on microscopic analysis of blood samples, as other specific tools are nonexistent. However, new developments in biotechnology, which include loop-mediated isothermal amplification as an adaptation to conventional PCR, as well as the antibody engineering that has allowed the development of Nanobody technology, offer new perspectives in both the detection and treatment of trypanosomiasis. In addition, recent data on parasite-induced B-cell memory destruction offer new insights into mechanisms of vaccine failure, and should lead us towards new strategies to overcome trypanosome defenses operating against the host immune system.
Mpandzou, Ghislain; Cespuglio, Raymond; Ngampo, Stéphane; Bandzouzi, Bébène; Bouteille, Bernard; Vincendeau, Philippe; Buguet, Alain
Gambian (Trypanosoma brucei gambiense) human African trypanosomiasis (HAT) evolves from the hemolymphatic stage 1, treated with pentamidine, to the meningoencephalitic stage 2, often treated with melarsoprol. This arseniate may provoke a deadly reactive encephalopathy. It is therefore crucial to diagnose precisely the stages of HAT, especially when clinical and biological examinations are doubtful. We present here the case of a 30-month old girl (E20 KOLNG) diagnosed with stage 1 HAT during a field survey in June 2007 in Congo. She was followed-up every six months for 18 months in a village dispensary facility at Mpouya. Her health status deteriorated in December 2008, although cerebrospinal fluid (CSF) white blood cell (WBC) count was normal. The child was hospitalized at Brazzaville and a daytime polysomnographic recording (electroencephalogram, electrooculogram, and electromyogram) was performed (Temec Vitaport 3® portable recorder) to avoid a new lumbar puncture. The child presented a complete polysomnographic syndrome of HAT with a major disturbance of the distribution of sleep and wake episodes and the occurrence of sleep onset REM periods (SOREMPs). The relapse at stage 2 was confirmed by a new CSF examination that showed an elevated WBC count (23cells·μL(-1)) with the presence of B lymphocytes. Melarsoprol treatment was undertaken. A post-treatment recording was immediately performed, showing the resolution of sleepwake pattern abnormalities. Another polysomnography, taken four months later, confirmed the normalization of sleep-wake patterns indicating healing. We therefore propose that polysomnography, being a non-invasive technique, should be used in children to alleviate burden caused by HAT staging procedures, especially regarding lumbar punctures in remote African villages.
Eperon, Gilles; Balasegaram, Manica; Potet, Julien; Mowbray, Charles; Valverde, Olaf; Chappuis, François
Treatment of second-stage gambiense human African trypanosomiasis relied on toxic arsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine, initially in monotherapy and more recently in combination with nifurtimox (NECT), has drastically improved the prognosis of treated patients. However, NECT logistic and nursing requirements remain obstacles to its deployment and use in peripheral health structures in rural sub-Saharan Africa. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development. The main scope of this article is to discuss the potential impact of new oral therapies to improve diagnosis-treatment algorithms and patients' access to treatment, and to contribute to reach the objectives of the recently launched gambiense human African trypanosomiasis elimination program.
Eperon, Gilles; Balasegaram, Manica; Potet, Julien; Mowbray, Charles; Valverde, Olaf; Chappuis, François
Treatment of second-stage gambiense human African trypanosomiasis relied on toxic arsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine, initially in monotherapy and more recently in combination with nifurtimox (NECT), has drastically improved the prognosis of treated patients. However, NECT logistic and nursing requirements remain obstacles to its deployment and use in peripheral health structures in rural sub-Saharan Africa. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development. The main scope of this article is to discuss the potential impact of new oral therapies to improve diagnosis-treatment algorithms and patients’ access to treatment, and to contribute to reach the objectives of the recently launched gambiense human African trypanosomiasis elimination program. PMID:25204360
Kennedy, Peter G.E.
Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. Current therapy with melarsoprol for CNS HAT has unacceptable side-effects with an overall mortality of 5%. This review discusses the issues of diagnosis and staging of CNS disease, its neuropathogenesis, and the possibility of new therapies for treating late-stage disease. PMID:14966556
Kennedy, Peter G E
Human African trypanosomiasis, also known as sleeping sickness, is a neglected disease, and it continues to pose a major threat to 60 million people in 36 countries in sub-Saharan Africa. Transmitted by the bite of the tsetse fly, the disease is caused by protozoan parasites of the genus Trypanosoma and comes in two types: East African human African trypanosomiasis caused by Trypanosoma brucei rhodesiense and the West African form caused by Trypanosoma brucei gambiense. There is an early or hemolymphatic stage and a late or encephalitic stage, when the parasites cross the blood-brain barrier to invade the central nervous system. Two critical current issues are disease staging and drug therapy, especially for late-stage disease. Lumbar puncture to analyze cerebrospinal fluid will remain the only method of disease staging until reliable noninvasive methods are developed, but there is no widespread consensus as to what exactly defines biologically central nervous system disease or what specific cerebrospinal fluid findings should justify drug therapy for late-stage involvement. All four main drugs used for human African trypanosomiasis are toxic, and melarsoprol, the only drug that is effective for both types of central nervous system disease, is so toxic that it kills 5% of patients who receive it. Eflornithine, alone or combined with nifurtimox, is being used increasingly as first-line therapy for gambiense disease. There is a pressing need for an effective, safe oral drug for both stages of the disease, but this will require a significant increase in investment for new drug discovery from Western governments and the pharmaceutical industry.
Lamour, Sabrina D.; Gomez-Romero, Maria; Vorkas, Panagiotis A.; Alibu, Vincent P.; Saric, Jasmina; Holmes, Elaine; Sternberg, Jeremy M.
Human African trypanosomiasis (HAT) remains a major neglected tropical disease in Sub-Saharan Africa. As clinical symptoms are usually non-specific, new diagnostic and prognostic markers are urgently needed to enhance the number of identified cases and optimise treatment. This is particularly important for disease caused by Trypanosoma brucei rhodesiense, where indirect immunodiagnostic approaches have to date been unsuccessful. We have conducted global metabolic profiling of plasma from T.b.rhodesiense HAT patients and endemic controls, using 1H nuclear magnetic resonance (NMR) spectroscopy and ultra-performance liquid chromatography, coupled with mass spectrometry (UPLC-MS) and identified differences in the lipid, amino acid and metabolite profiles. Altogether 16 significantly disease discriminatory metabolite markers were found using NMR, and a further 37 lipid markers via UPLC-MS. These included significantly higher levels of phenylalanine, formate, creatinine, N-acetylated glycoprotein and triglycerides in patients relative to controls. HAT patients also displayed lower concentrations of histidine, sphingomyelins, lysophosphatidylcholines, and several polyunsaturated phosphatidylcholines. While the disease metabolite profile was partially consistent with previous data published in experimental rodent infection, we also found unique lipid and amino acid profile markers highlighting subtle but important differences between the host response to trypanosome infections between animal models and natural human infections. Our results demonstrate the potential of metabolic profiling in the identification of novel diagnostic biomarkers and the elucidation of pathogenetic mechanisms in this disease. PMID:26505639
Lamour, Sabrina D; Gomez-Romero, Maria; Vorkas, Panagiotis A; Alibu, Vincent P; Saric, Jasmina; Holmes, Elaine; Sternberg, Jeremy M
Human African trypanosomiasis (HAT) remains a major neglected tropical disease in Sub-Saharan Africa. As clinical symptoms are usually non-specific, new diagnostic and prognostic markers are urgently needed to enhance the number of identified cases and optimise treatment. This is particularly important for disease caused by Trypanosoma brucei rhodesiense, where indirect immunodiagnostic approaches have to date been unsuccessful. We have conducted global metabolic profiling of plasma from T.b.rhodesiense HAT patients and endemic controls, using 1H nuclear magnetic resonance (NMR) spectroscopy and ultra-performance liquid chromatography, coupled with mass spectrometry (UPLC-MS) and identified differences in the lipid, amino acid and metabolite profiles. Altogether 16 significantly disease discriminatory metabolite markers were found using NMR, and a further 37 lipid markers via UPLC-MS. These included significantly higher levels of phenylalanine, formate, creatinine, N-acetylated glycoprotein and triglycerides in patients relative to controls. HAT patients also displayed lower concentrations of histidine, sphingomyelins, lysophosphatidylcholines, and several polyunsaturated phosphatidylcholines. While the disease metabolite profile was partially consistent with previous data published in experimental rodent infection, we also found unique lipid and amino acid profile markers highlighting subtle but important differences between the host response to trypanosome infections between animal models and natural human infections. Our results demonstrate the potential of metabolic profiling in the identification of novel diagnostic biomarkers and the elucidation of pathogenetic mechanisms in this disease.
Clerinx, J; Vlieghe, E; Asselman, V; Van de Casteele, S; Maes, M B; Lejon, V
A Belgian traveller was diagnosed with human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense nine days after visiting the Masai Mara area in Kenya. He presented with an inoculation chancre and was treated with suramin within four days of fever onset. Two weeks earlier, HAT was also reported in a German traveller who had visited the Masai Mara area. Because no cases have occurred in the area for over 12 years, this may indicate a focal cluster of HAT.
Wengert, Oliver; Kopp, Marcel; Siebert, Eberhard; Stenzel, Werner; Hegasy, Guido; Suttorp, Norbert; Stich, August; Zoller, Thomas
Human African trypanosomiasis (HAT), also referred to as "sleeping sickness", is caused by the parasite Trypanosoma brucei. Diagnosing imported HAT outside endemic areas is difficult and diagnosis is often delayed. We report a case of imported human African trypanosomiasis caused by Trypanosoma brucei gambiense with an unusually long incubation period of at least 7 years. A 33 year old male African patient, a former resident of Cameroon, presented with a 4-month history of progressive personality changes. A few weeks before presentation the patient had first been admitted to a psychiatric ward and received antidepressant treatment, until a lumbar puncture showed pleocytosis and then antibiotic treatment for suspected neuroborreliosis was initiated. The patient continued to deteriorate during antibiotic treatment and became increasingly lethargic. Under antiparasitic and anti-inflammatory treatment, the condition of the patient gradually improved over the following months and he recovered completely after 24 months of follow-up. This well-documented case illustrates typical difficulties in establishing the correct diagnosis outside endemic areas and provides an overview of typical clinical, neuropathological and neuroimaging findings in T. b. gambiense trypanosomiasis, guiding the clinician in establishing the correct diagnosis in this rare disease.
Sudarshi, Darshan; Brown, Mike
Human African trypanosomiasis (HAT) or sleeping sickness is a parasitic disease, acquired by the bite of an infected tsetse fly. In non-endemic countries HAT is rare, and therefore the diagnosis may be delayed leading to potentially fatal consequences. In this article the clinical presentation, diagnosis and treatment of the two forms of HAT are outlined. Rhodesiense HAT is an acute illness that presents in tourists who have recently visited game parks in Eastern or Southern Africa, whereas Gambiense HAT has a more chronic clinical course, in individuals from West or Central Africa.
Gilbert, Jennifer A; Medlock, Jan; Townsend, Jeffrey P; Aksoy, Serap; Ndeffo Mbah, Martial; Galvani, Alison P
Human African trypanosomiasis (HAT), transmitted by tsetse flies, has historically infected hundreds of thousands of individuals annually in sub-Saharan Africa. Over the last decade, concerted control efforts have reduced reported cases to below 10,000 annually, bringing complete elimination within reach. A potential technology to eliminate HAT involves rendering the flies resistant to trypanosome infection. This approach can be achieved through the introduction of transgenic Sodalis symbiotic bacteria that have been modified to produce a trypanocide, and propagated via Wolbachia symbionts, which confer a reproductive advantage to the paratransgenic tsetse. However, the population dynamics of these symbionts within tsetse flies have not yet been evaluated. Specifically, the key factors that determine the effectiveness of paratransgenesis have yet to be quantified. To identify the impact of these determinants on T.b. gambiense and T.b. rhodesiense transmission, we developed a mathematical model of trypanosome transmission that incorporates tsetse and symbiont population dynamics. We found that fecundity and mortality penalties associated with Wolbachia or recombinant Sodalis colonization, probabilities of vertical transmission, and tsetse migration rates are fundamental to the feasibility of HAT elimination. For example, we determined that HAT elimination could be sustained over 25 years when Wolbachia colonization minimally impacted fecundity or mortality, and when the probability of recombinant Sodalis vertical transmission exceeded 99.9%. We also found that for a narrow range of recombinant Sodalis vertical transmission probability (99.9-90.6% for T.b. gambiense and 99.9-85.8% for T.b. rhodesiense), cumulative HAT incidence was reduced between 30% and 1% for T.b. gambiense and between 21% and 3% for T.b. rhodesiense, although elimination was not predicted. Our findings indicate that fitness and mortality penalties associated with paratransgenic symbionts, as well
Gilbert, Jennifer A.; Medlock, Jan; Townsend, Jeffrey P.; Aksoy, Serap
Human African trypanosomiasis (HAT), transmitted by tsetse flies, has historically infected hundreds of thousands of individuals annually in sub-Saharan Africa. Over the last decade, concerted control efforts have reduced reported cases to below 10,000 annually, bringing complete elimination within reach. A potential technology to eliminate HAT involves rendering the flies resistant to trypanosome infection. This approach can be achieved through the introduction of transgenic Sodalis symbiotic bacteria that have been modified to produce a trypanocide, and propagated via Wolbachia symbionts, which confer a reproductive advantage to the paratransgenic tsetse. However, the population dynamics of these symbionts within tsetse flies have not yet been evaluated. Specifically, the key factors that determine the effectiveness of paratransgenesis have yet to be quantified. To identify the impact of these determinants on T.b. gambiense and T.b. rhodesiense transmission, we developed a mathematical model of trypanosome transmission that incorporates tsetse and symbiont population dynamics. We found that fecundity and mortality penalties associated with Wolbachia or recombinant Sodalis colonization, probabilities of vertical transmission, and tsetse migration rates are fundamental to the feasibility of HAT elimination. For example, we determined that HAT elimination could be sustained over 25 years when Wolbachia colonization minimally impacted fecundity or mortality, and when the probability of recombinant Sodalis vertical transmission exceeded 99.9%. We also found that for a narrow range of recombinant Sodalis vertical transmission probability (99.9–90.6% for T.b. gambiense and 99.9–85.8% for T.b. rhodesiense), cumulative HAT incidence was reduced between 30% and 1% for T.b. gambiense and between 21% and 3% for T.b. rhodesiense, although elimination was not predicted. Our findings indicate that fitness and mortality penalties associated with paratransgenic symbionts, as
This report provides a review and analysis of the research landscape for three diseases - Chagas disease, human African trypanosomiasis and leishmaniasis - that disproportionately afflict poor and remote populations with limited access to health services. It represents the work of the disease reference group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis (DRG3) which was established to identify key research priorities through review of research evidence and input from stakeholders' consultations. The diseases, which are caused by related protozoan parasites, are described in terms of their epidemiology and diseases burden, clinical forms and pathogenesis, HIV coinfection, diagnosis, drugs and drug resistance, vaccines, vector control, and health-care interventions. Priority areas for research are identified based on criteria such as public health relevance, benefit and impact on poor populations and equity, and feasibility. The priorities are found in the areas of diagnostics, drugs, vector control, asymptomatic infection, economic analysis of treatment and vector control methods, and in some specific issues such as surveillance methods or transmission-blocking vaccines for particular diseases. This report will be useful to researchers, policy and decision-makers, funding bodies, implementation organizations, and civil society. This is one of ten disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at: www.who.int/tdr/stewardship/global_report/en/index.html.
Mwanakasale, Victor; Songolo, Peter
We conducted a situation analysis of human African trypanosomiasis (HAT) in Zambia from January 2000 to April 2007. The aim of this survey was to identify districts in Zambia that were still recording cases of HAT. Three districts namely, Mpika, Chama, and Chipata were found to be still reporting cases of HAT and thus lay in HAT transmission foci in North Eastern Zambia. During the period under review, 24 cases of HAT were reported from these three districts. We thereafter reviewed literature on the occurrence of HAT in Zambia from the early 1960s to mid 1990s. This revealed that HAT transmission foci were widespread in Western, North Western, Lusaka, Eastern, Luapula, and Northern Provinces of Zambia during this period. In this article we have tried to give possible reasons as to why the distribution of HAT transmission foci is so different between before and after 2000 when there has been no active national tsetse fly and trypanosomiasis control program in Zambia.
Arias, José L; Unciti-Broceta, Juan D; Maceira, José; Del Castillo, Teresa; Hernández-Quero, José; Magez, Stefan; Soriano, Miguel; García-Salcedo, José A
Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D,L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogen Trypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug for T. b. gambiense acute infection. An in vitro effectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore, in vivo therapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases.
Blum, J A; Neumayr, A L; Hatz, C F
Human African trypanosomiasis (HAT) or sleeping sickness is caused by the protozoan parasites Trypanosoma brucei (T.b.) gambiense (West African form) and T.b. rhodesiense (East African form) that are transmitted by the bite of the tsetse fly, Glossina spp.. Whereas most patients in endemic populations are infected with T.b. gambiense, most tourists are infected with T.b. rhodesiense. In endemic populations, T.b. gambiense HAT is characterized by chronic and intermittent fever, headache, pruritus, and lymphadenopathy in the first stage and by sleep disturbances and neuro-psychiatric disorders in the second stage. Recent descriptions of the clinical presentation of T.b. rhodesiense in endemic populations show a high variability in different foci. The symptomatology of travellers is markedly different from the usual textbook descriptions of African HAT patients. The onset of both infections is almost invariably an acute and febrile disease. Diagnosis and treatment are difficult and rely mostly on old methods and drugs. However, new molecular diagnostic technologies are under development. A promising new drug combination is currently evaluated in a phase 3 b study and further new drugs are under evaluation.
Ferrins, Lori; Rahmani, Raphaël; Baell, Jonathan B
Human African trypanosomiasis (HAT) has been neglected for a long time. The most recent drug to treat this disease, eflornithine, was approved by the US FDA in 2000. Current treatments exhibit numerous problematic side effects and are often ineffective against the debilitating CNS resident stage of the disease. Fortunately, several partnerships and initiatives have been formed over the last 20 years in an effort to eradicate HAT, along with a number of other neglected diseases. This has led to an increasing number of foundations and research institutions that are currently working on the development of new drugs for HAT and tools with which to diagnose and treat patients. New biochemical pathways as therapeutic targets are emerging, accompanied by increasing numbers of new antitrypanosomal compound classes. The future looks promising that this collaborative approach will facilitate eagerly awaited breakthroughs in the treatment of HAT.
Okello, Anna L.; Welburn, Susan C.
Rapid changes in human behavior, resource utilization, and other extrinsic environmental factors continue to threaten the current distribution of several endemic and historically neglected zoonoses in many developing regions worldwide. There are numerous examples of zoonotic diseases which have circulated within relatively localized geographical areas for some time, before emerging into new regions as a result of changing human, environmental, or behavioral dynamics. While the world’s focus is currently on the Ebola virus gaining momentum in western Africa, another pertinent example of this phenomenon is zoonotic human African trypanosomiasis (HAT), endemic to south and eastern Africa, and spread via infected cattle. In recent years, the ongoing northwards spread of this disease in the country has posed a serious public health threat to the human population of Uganda, increasing the pressure on both individual families and government services to control the disease. Moreover, the emergence of HAT into new areas of Uganda in recent years exemplifies the important role of veterinary policy in mitigating the severe human health and economic impacts of zoonotic disease. The systemic challenges surrounding the development and enforcement of veterinary policy described here are similar across sub-Saharan Africa, highlighting the necessity to consider and support zoonotic disease control in broader human and animal health systems strengthening and associated development programs on the continent. PMID:25405148
AD-A237 230_ DEVELOPMENT OF A NEW CHEMOTHERAPY FOR HUMAN AFRICAN TRYPANOSOMIASIS BY USING AN ANIMAL MODEL: SURAMIN WITH DL..DIFLUOROMETHYLORNITHINE... Chemotherapy for African trypanosomiasis by polyamine biosynthesis inhibition.) FINAL PROGRESS REPORT Allen B. Clarkson, Jr., Ph.D. September 14, 1989...AF 061 11. TITLE (include Security Classification) "Development of a New Chemotherapy for Human African Trypanosomiasis by Using an Animal Model
AD-A2 3 7 231 AD ______________ DEVELOPMENT OF A NEW CHEMOTHERAPY FOR HUMAN AFRICAN TRYPANOSOMIASIS BY USING AN ANIMAL MODEL: SURAMIN WITH DL...DIFLUOROMETHYLORNITHINE ( Chemotherapy for African trypanosomiasis by polyamine biosynthesis inhibition.) ANNUAL PROGRESS REPORT -- YEAR TWO Allen B... Chemotherapy for Human African Trypanosomiasis by Using an Animal Model: Suramin with DL- a- Difluoromethylornithine" 12. PERSONAL AUTHOR(S) Clarkson, Allen
Human African trypanosomiasis (HAT) or sleeping sickness is caused by protozoan parasites Trypanosoma brucei gambiense and T. b. rhodesiense. Despite the enormous technological progress in molecular parasitology in recent years, the diagnosis of HAT is still problematic due to the lack of specific tools. To date, there are two realities when it comes to HAT; the first one being the world of modern experimental laboratories, equipped with the latest state-of-the-art technology, and the second being the world of HAT diagnosis, where the latest semi-commercial test was introduced 30 years ago (Magnus et al. 1978). Hence, it appears that the lack of progress in HAT diagnosis is not primarily due to a lack of scientific interest or a lack of research funds, but mainly results from the many obstacles encountered in the translation of basic research into field-applicable diagnostics. This review will provide an overview of current diagnostic methods and highlight specific difficulties in solving the shortcomings of these methods. Future perspectives for accurate, robust, affordable diagnostics will be discussed as well.
Rutto, Jane Jemeli; Osano, Odipo; Thuranira, Elias Gitonga; Kurgat, Richard Kiptum; Odenyo, Victor Agab Omondi
Background Kenya and Uganda have reported different Human African Trypanosomiasis incidences in the past more than three decades, with the latter recording more cases. This cross-sectional study assessed the demographic characteristics, tsetse and trypanosomiasis control practices, socio-economic and cultural risk factors influencing Trypanosoma brucei rhodesiense (T.b.r.) infection in Teso and Busia Districts, Western Kenya and Tororo and Busia Districts, Southeast Uganda. A conceptual framework was postulated to explain interactions of various socio-economic, cultural and tsetse control factors that predispose individuals and populations to HAT. Methods A cross-sectional household survey was conducted between April and October 2008. Four administrative districts reporting T.b.r and lying adjacent to each other at the international boundary of Kenya and Uganda were purposely selected. Household data collection was carried out in two villages that had experienced HAT and one other village that had no reported HAT case from 1977 to 2008 in each district. A structured questionnaire was administered to 384 randomly selected household heads or their representatives in each country. The percent of respondents giving a specific answer was reported. Secondary data was also obtained on socio-economic and political issues in both countries. Results Inadequate knowledge on the disease cycle and intervention measures contributed considerable barriers to HAT, and more so in Uganda than in Kenya. Gender-associated socio-cultural practices greatly predisposed individuals to HAT. Pesticides-based crop husbandry in the 1970's reportedly reduced vector population while vegetation of coffee and banana's and livestock husbandry directly increased occurrence of HAT. Livestock husbandry practices in the villages were strong predictors of HAT incidence. The residents in Kenya (6.7%) applied chemoprophylaxis and chemotherapeutic controls against trypanosomiasis to a larger extent than
Gouteux, J P; Kounda Gboumbi, J C; Noutoua, L; D'Amico, F; Bailly, C; Roungou, J B
A study using bipyramid tetse fly traps in the Nola-Bilolo sleeping sickness focus (Central African Republic) reveals ecological and behavioural differences between two vectors, Glossina palpalis palpalis and G. fuscipes fuscipes. The latter species inhabits mainly open water sites and surrounding forest, whereas G. p. palpalis occurs mainly in coffe plantations near villages. Consequently, the man-fly contact differs considerably according to the species. The intensity of trypanosomiasis transmission, estimated by the probable distribution of cases, showed significant positive correlation with the density of the flies. Analysis of the fly blood meals in two villages show that, unlike G. g. palpalis, G. f. fuscipes feeds on men more than on pigs. Trypanosoma vivax infection was observed only in G. fuscipes fuscipes. The differences in occupation of the environment between the two vectors must be taken in account in trapping programmes which may modify this distribution.
Seke Etet, Paul F.; Fawzi Mahomoodally, M.
Human African trypanosomiasis (HAT) is a fatal if untreated fly-borne neuroinflammatory disease caused by protozoa of the species Trypanosoma brucei (T.b.). The increasing trend of HAT cases has been reversed, but according to WHO experts, new epidemics of this disease could appear. In addition, HAT is still a considerable burden for life quality and economy in 36 sub-Saharan Africa countries with 15–20 million persons at risk. Following joined initiatives of WHO and private partners, the fight against HAT was re-engaged, resulting in considerable breakthrough. We present here what is known at this day about HAT etiology and pathogenesis and the new insights in the development of accurate tools and tests for disease staging and severity monitoring in the field. Also, we elaborate herein the promising progresses made in the development of less toxic and more efficient trypanocidal drugs including the potential of medicinal plants and related alternative drug therapies. PMID:22593674
Seke Etet, Paul F; Mahomoodally, M Fawzi
Human African trypanosomiasis (HAT) is a fatal if untreated fly-borne neuroinflammatory disease caused by protozoa of the species Trypanosoma brucei (T.b.). The increasing trend of HAT cases has been reversed, but according to WHO experts, new epidemics of this disease could appear. In addition, HAT is still a considerable burden for life quality and economy in 36 sub-Saharan Africa countries with 15-20 million persons at risk. Following joined initiatives of WHO and private partners, the fight against HAT was re-engaged, resulting in considerable breakthrough. We present here what is known at this day about HAT etiology and pathogenesis and the new insights in the development of accurate tools and tests for disease staging and severity monitoring in the field. Also, we elaborate herein the promising progresses made in the development of less toxic and more efficient trypanocidal drugs including the potential of medicinal plants and related alternative drug therapies.
Background African trypanosomiasis is a parasitic infection sporadically imported to Europe by tourists or immigrants returning from endemic areas. We present the first and an unusual case of East African trypanosomiasis imported to Poland by a patient returning from a tourist trip to Uganda and Rwanda, which was successfully treated with pentamidine. Case presentation A 61-year-old Polish man was admitted to the Department because of high-grade fever and multi-organ dysfunction after a tourist trip to East Africa. He experienced a single tsetse fly bite during a safari trip to the Queen Elizabeth National Park in Uganda. On admission, his clinical status was severe, with high fever of 41ºC, preceded by chills, bleeding from the gums and oral mucosa, haemorrhages at the sites of venipuncture, numerous ecchymoses, fine-spotted skin rash, tachycardia, hepatosplenomegaly, dehydration, jaundice, dyspnoea, hypoxaemia, generalised oedema and oliguria. There was a typical non-painful trypanosomal chancre with central necrosis and peripheral erythema on his left arm. Laboratory investigations showed leucopenia, thrombocytopenia, haemolytic anaemia, hyperbilirubinaemia, hypoglycaemia, elevated creatinine and urea, high activity of aminotransferases, elevated levels of inflammatory markers, hypoproteinaemia, proteinuria, abnormal clotting and bleeding times, low fibrinogen level, metabolic acidosis, and electrolyte disturbances. A peripheral blood smear showed numerous Trypanosoma brucei trypomastigotes with a massive parasitaemia of 100,000/μl. T. brucei rhodesiense subspecies was finally identified on the basis of the characteristic serum resistance-associated gene using a polymerase chain reaction, and a seroconversion of specific immunoglobulin M and G antibodies in the peripheral blood by enzyme-linked immunosorbent assay. Serological tests for T. brucei gambiense subspecies were negative. A severe clinical course of acute rhodesiense trypanosomiasis with renal
Elliott, Ivo; Patel, Trupti; Shah, Jagrit; Venkatesan, Pradhib
West-African trypanosomiasis caused by Trypanosoma brucei gambiense is a rare imported infection presenting with somnolence, lymphadenopathy and wide-ranging neurological symptoms. A 67-year-old Caucasian man presented with a 10-month history of cognitive deterioration, ataxic gait, somnolence and urinary incontinence. His symptoms had progressed more rapidly over the course of a month prior to admission. Serological testing confirmed a diagnosis of West-African trypanosomiasis. The patient was successfully treated with eflornithine and made a good recovery. West-African trypanosomiasis should be considered in the differential diagnosis of unexplained cognitive decline in those with a relevant travel history. If left untreated, the condition is universally fatal.
Yaro, M; Munyard, K A; Stear, M J; Groth, D M
African Animal Trypanosomiasis (AAT) is endemic in at least 37 of the 54 countries in Africa. It is estimated to cause direct and indirect losses to the livestock production industry in excess of US$ 4.5 billion per annum. A century of intervention has yielded limited success, owing largely to the extraordinary complexity of the host-parasite interaction. Trypanotolerance, which refers to the inherent ability of some African livestock breeds, notably Djallonke sheep, N'Dama cattle and West African Dwarf goats, to withstand a trypanosomiasis challenge and still remain productive without any form of therapy, is an economically sustainable option for combatting this disease. Yet trypanotolerance has not been adequately exploited in the fight against AAT. In this review, we describe new insights into the genetic basis of trypanotolerance and discuss the potential of exploring this phenomenon as an integral part of the solution for AAT, particularly, in the context of African animal production systems.
Ruiz, José Antonio; Simarro, Pere P.; Josenando, Teofilo
OBJECTIVE: To update the epidemiological status of human African trypanosomiasis (HAT), also known as sleeping sickness, in the Quiçama focus, province of Bengo, Angola, and to establish a HAT control programme. METHODS: In 1997, 8796 people (the population of 31 villages) were serologically screened for Trypanosoma brucei gambiense, the causative agent of HAT. In 1998 and 1999, surveys were carried out in villages where HAT cases had been identified in 1997. Individuals were screened using the card agglutination trypanosomiasis test (CATT), and then examined for the presence of the parasite. CATT- positive individuals in whom the presence of the parasite could not be confirmed were further tested with the CATT using serum dilutions, and those with a positive antibody end titre of 1-in-4 or above were followed-up. Patients with < or =10 white cells/micro l and no trypanosomes in their cerebrospinal fluid (CSF) were classified as being in the first stage of the disease. Vector control was not considered necessary or feasible. FINDINGS: The main transmission areas were on the Kwanza riverbanks, where 5042 inhabitants live. In 1997, the HAT prevalence was 1.97%, but this decreased to 0.55% in 1998 and to 0.33% in 1999. The relapse rate was 3% in patients treated with pentamidine and 3.5% in patients treated with melarsoprol. In patients treated with pentamidine, there was no difference in the relapse rate for patients with initial CSF white cell counts of 0-5 cells/ micro l or 6-10 cells/micro l. The overall mortality rate was 0.6% and the rate of reactive arsenical encephalopathy among the melarsoprol-treated patients was 1.7%. CONCLUSION: The epidemiological status of the disease was updated and the transmission areas were defined. The control methods implemented allowed the disease prevalence to be reduced. PMID:12378293
Tatipaka, Hari Babu; Gillespie, J. Robert; Chatterjee, Arnab K.; Norcross, Neil R.; Hulverson, Matthew A.; Ranade, Ranae M.; Nagendar, Pendem; Creason, Sharon A.; McQueen, Joshua; Duster, Nicole A.; Nagle, Advait; Supek, Frantisek; Molteni, Valentina; Wenzler, Tanja; Brun, Reto; Glynne, Richard; Buckner, Frederick S.; Gelb, Michael H.
A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl) oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl) imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable drug-like properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent anti-parasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis. PMID:24354316
Tatipaka, Hari Babu; Gillespie, J Robert; Chatterjee, Arnab K; Norcross, Neil R; Hulverson, Matthew A; Ranade, Ranae M; Nagendar, Pendem; Creason, Sharon A; McQueen, Joshua; Duster, Nicole A; Nagle, Advait; Supek, Frantisek; Molteni, Valentina; Wenzler, Tanja; Brun, Reto; Glynne, Richard; Buckner, Frederick S; Gelb, Michael H
A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.
Gilbert, Ian H
Target-based approaches for human African trypanosomiasis (HAT) and related parasites can be a valuable route for drug discovery for these diseases. However, care needs to be taken in selection of both the actual drug target and the chemical matter that is developed. In this article, potential criteria to aid target selection are described. Then the physiochemical properties of typical oral drugs are discussed and compared to those of known anti-parasitics.
Kaiser, Marcel; Avery, Vicky M.
The screening of a focused library identified FTY720 (Fingolimod; Gilenya) as a potent selective antitrypanosomal compound active against Trypanosoma brucei gambiense and T. brucei rhodesiense, the causative agents of human African trypanosomiasis (HAT). This is the first report of trypanocidal activity for FTY720, an oral drug registered for the treatment of relapsing multiple sclerosis, and the characterization of sphingolipids as a potential new class of compounds for HAT. PMID:26666915
Hasker, Epco; Lumbala, Crispin; Lutumba, Pascal; de Vlas, Sake J.; van de Klundert, Joris
To eliminate and eradicate gambiense human African trypanosomiasis (HAT), maximizing the effectiveness of active case finding is of key importance. The progression of the epidemic is largely influenced by the planning of these operations. This paper introduces and analyzes five models for predicting HAT prevalence in a given village based on past observed prevalence levels and past screening activities in that village. Based on the quality of prevalence level predictions in 143 villages in Kwamouth (DRC), and based on the theoretical foundation underlying the models, we consider variants of the Logistic Model—a model inspired by the SIS epidemic model—to be most suitable for predicting HAT prevalence levels. Furthermore, we demonstrate the applicability of this model to predict the effects of planning policies for screening operations. Our analysis yields an analytical expression for the screening frequency required to reach eradication (zero prevalence) and a simple approach for determining the frequency required to reach elimination within a given time frame (one case per 10000). Furthermore, the model predictions suggest that annual screening is only expected to lead to eradication if at least half of the cases are detected during the screening rounds. This paper extends knowledge on control strategies for HAT and serves as a basis for further modeling and optimization studies. PMID:27657937
Baker, Nicola; de Koning, Harry P; Mäser, Pascal; Horn, David
Melarsoprol and pentamidine represent the two main classes of drugs, the arsenicals and diamidines, historically used to treat the diseases caused by African trypanosomes: sleeping sickness in humans and Nagana in livestock. Cross-resistance to these drugs was first observed over 60 years ago and remains the only example of cross-resistance among sleeping sickness therapies. A Trypanosoma brucei adenosine transporter is well known for its role in the uptake of both drugs. More recently, aquaglyceroporin 2 (AQP2) loss of function was linked to melarsoprol-pentamidine cross-resistance. AQP2, a channel that appears to facilitate drug accumulation, may also be linked to clinical cases of resistance. Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites.
Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein–encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology. PMID:24763584
Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein-encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.
Babokhov, Peter; Sanyaolu, Adekunle O; Oyibo, Wellington A; Fagbenro-Beyioku, Adetayo F; Iriemenam, Nnaemeka C
Despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human African trypanosomiasis (HAT) remains a challenging task. The four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-Saharan Africa. Pentamidine and suramin are limited by their effectiveness against the only first stage of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. In addition, melarsoprol and eflornithine (two second stage drugs) each have disadvantages of their own. The former is toxic and has increasing treatment failures while the latter is expensive, laborious to administer, and lacks efficacy against T. b. rhodesiense. Furthermore, melarsoprol's toxicity and decreasing efficacy are glaring problems and phasing out the drug as a frontline treatment against T. b. gambiense is now possible with the emergence of competent, safe combination chemotherapies such as nifurtimox-eflornithine combination treatment (NECT). The future of eflornithine, on the other hand, is more promising. The drug is useful in the context of combination chemotherapy and potential orally administered analogues. Due to the limits of monotherapies, greater emphasis should be placed on the research and development of combination chemotherapies, based on the successful clinical tests with NECT and its current use as a frontline anti-trypanosomiasis treatment. This review discussed the current and future chemotherapy strategies for the treatment of HAT.
Holt, Hannah R.; Selby, Richard; Guitian, Javier
Background Control operations targeting Animal African Trypanosomiasis and its primary vector, the tsetse, were covering approximately 128,000 km2 of Africa in 2001, which is a mere 1.3% of the tsetse infested area. Although extensive trypanosomiasis and tsetse (T&T) control operations have been running since the beginning of the 20th century, Animal African Trypanosomiasis is still a major constraint of livestock production in sub-Saharan Africa. Methodology/Principal Findings We performed a systematic review of the existing literature describing T&T control programmes conducted in a selection of five African countries, namely Burkina Faso, Cameroon, Ethiopia, Uganda and Zambia, between 1980 and 2015. Sixty-eight documents were eventually selected from those identified by the database search. This was supplemented with information gathered through semi-structured interviews conducted with twelve key informants recruited in the study countries and selected based on their experience and knowledge of T&T control. The combined information from these two sources was used to describe the inputs, processes and outcomes from 23 major T&T control programmes implemented in the study countries. Although there were some data gaps, involvement of the target communities and sustainability of the control activities were identified as the two main issues faced by these programmes. Further, there was a lack of evaluation of these control programmes, as well as a lack of a standardised methodology to conduct such evaluations. Conclusions/Significance Past experiences demonstrated that coordinated and sustained control activities require careful planning, and evidence of successes, failures and setbacks from past control programmes represent a mine of information. As there is a lack of evaluation of these programmes, these data have not been fully exploited for the design, analyses and justification of future control programmes. PMID:28027299
Unciti-Broceta, Juan D.; Arias, José L.; Maceira, José; Soriano, Miguel; Ortiz-González, Matilde; Hernández-Quero, José; Muñóz-Torres, Manuel; de Koning, Harry P.; Magez, Stefan; Garcia-Salcedo, José A.
African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs. PMID:26110623
Unciti-Broceta, Juan D; Arias, José L; Maceira, José; Soriano, Miguel; Ortiz-González, Matilde; Hernández-Quero, José; Muñóz-Torres, Manuel; de Koning, Harry P; Magez, Stefan; Garcia-Salcedo, José A
African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.
Kuriakose, Shiby M.; Singh, Rani; Uzonna, Jude E.
Pathogens, such as bacteria, viruses, and parasites, possess specific molecules or proteins that are recognized by several host innate immune receptors, leading to the activation of several intracellular signaling molecules and pathways. The magnitude and quality of these events significantly affect the outcome of infection. African trypanosomes, including Trypanosoma congolense, are capable of manipulating the host immune response, including the activity of macrophages, which are the key immune cells that contribute to the immunopathogenesis of African trypanosomiasis. Although it is known that immune hyperactivation and excessive pro-inflammatory cytokine production are the hallmarks of African trypanosomiasis, the mechanisms through which these events are triggered are poorly defined. However, it is known that macrophages may play a significant role in these processes, because phagocytosis of trypanosomes by macrophages initiates intracellular signal transduction cascades that lead to the release of pro-inflammatory cytokines and alteration in cell function. This review highlights recent progress in our understanding of the innate immune receptors, signaling pathways, and transcription factors involved in T. congolense-induced pro-inflammatory cytokine production in macrophages. It will reveal the existence of complex signaling events through which the parasite modulates the host immune response, thus identifying novel targets that could aid in designing strategies to effectively control the disease. PMID:27242788
Changasi, Robert Emojong
Human African Trypanosomiasis (HAT) transmitted by the tsetse fly continues to be a public health issue, despite more than a century of research. There are two types of the disease, the chronic gambiense and the acute rhodesiense-HAT. Fly abundance and distribution have been affected by changes in land-use patterns and climate. However, disease transmission still continues. Here, we review some aspects of HAT ecoepidemiology in the context of altered infestation patterns and maintenance of the transmission cycle as well as emerging options in disease and vector control. PMID:27034944
Lejon, V.; Büscher, P.; Sema, N. H.; Magnus, E.; Van Meirvenne, N.
LATEX/IgM, a rapid agglutination test for the semi-quantitative detection of IgM in cerebrospinal fluid of patients with African trypanosomiasis, is described in this article. The lyophilized reagent has been designed for field use and remains stable at 45 degrees C for one year. The test has been evaluated on cerebrospinal fluid samples from trypanosome-infected and non-infected patients, by comparison with commercial latex agglutination, radial immunodiffusion, and nephelometry. All test systems yielded similar results. PMID:10191550
Rodgers, Jean; Stone, Trevor W; Barrett, Michael P; Bradley, Barbara; Kennedy, Peter G E
Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in
Wamwiri, Florence Njeri; Changasi, Robert Emojong
Human African Trypanosomiasis (HAT) transmitted by the tsetse fly continues to be a public health issue, despite more than a century of research. There are two types of the disease, the chronic gambiense and the acute rhodesiense-HAT. Fly abundance and distribution have been affected by changes in land-use patterns and climate. However, disease transmission still continues. Here, we review some aspects of HAT ecoepidemiology in the context of altered infestation patterns and maintenance of the transmission cycle as well as emerging options in disease and vector control.
Büscher, Philippe; Deborggraeve, Stijn
A variety of molecular diagnostic tests for human African trypanosomiasis (HAT) (sleeping sickness) has been developed. Some are effectively used for research and confirmation diagnosis in travel medicine, usually following non-standardized protocols. Others have become commercially available as diagnostic kits. WHO aims to eliminate HAT as a public health problem by the year 2020, and zero transmission by the year 2030. This article gives an overview of the recent progress in molecular diagnostics for sleeping sickness, including the most recent data on test performances. Also discussed is how molecular diagnostics can play an important role in the process toward the elimination of HAT.
Mansfield, John M.; Wallace, John H.
Adult New Zealand white rabbits were experimentally infected with a parasitic African hemoflagellate, Trypanosoma congolense, and were subsequently tested for in vivo and in vitro aspects of cell-mediated immune function. Chronically infected rabbits were sensitized to mycobacterial protein and skin-tested with purified protein derivative; all infected animals demonstrated much milder skin-test responses to antigen than control groups. Similarly, peripheral blood lymphocyte responses in vitro to purified protein derivative and, as well, to phytohemagglutinin were markedly suppressed. Supernatant fluids of antigen-stimulated lymph node cell cultures from T. congolense-infected rabbits failed to demonstrate migration inhibitory factor activity but did possess normal levels of blastogenic factor activity. An active infection was necessary for demonstration of suppressed immune responses, and components present in infected rabbit serum were apparently not responsible for the observed abnormalities. Suppression of T-lymphocyte subpopulations may well explain the occurrence of numerous immunological aberrations arising during human and animal infections with the African trypanosomes. PMID:4854532
Sutherland, C Simone; Yukich, Joshua; Goeree, Ron; Tediosi, Fabrizio
Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and
Background Following World Health Assembly resolutions 50.36 in 1997 and 56.7 in 2003, the World Health Organization (WHO) committed itself to supporting human African trypanosomiasis (HAT)-endemic countries in their efforts to remove the disease as a public health problem. Mapping the distribution of HAT in time and space has a pivotal role to play if this objective is to be met. For this reason WHO launched the HAT Atlas initiative, jointly implemented with the Food and Agriculture Organization of the United Nations, in the framework of the Programme Against African Trypanosomosis. Results The distribution of HAT is presented for 23 out of 25 sub-Saharan countries having reported on the status of sleeping sickness in the period 2000 - 2009. For the two remaining countries, i.e. Angola and the Democratic Republic of the Congo, data processing is ongoing. Reports by National Sleeping Sickness Control Programmes (NSSCPs), Non-Governmental Organizations (NGOs) and Research Institutes were collated and the relevant epidemiological data were entered in a database, thus incorporating (i) the results of active screening of over 2.2 million people, and (ii) cases detected in health care facilities engaged in passive surveillance. A total of over 42 000 cases of HAT and 6 000 different localities were included in the database. Various sources of geographic coordinates were used to locate the villages of epidemiological interest. The resulting average mapping accuracy is estimated at 900 m. Conclusions Full involvement of NSSCPs, NGOs and Research Institutes in building the Atlas of HAT contributes to the efficiency of the mapping process and it assures both the quality of the collated information and the accuracy of the outputs. Although efforts are still needed to reduce the number of undetected and unreported cases, the comprehensive, village-level mapping of HAT control activities over a ten-year period ensures a detailed and reliable representation of the known
Bastos, I M D; Motta, F N; Grellier, P; Santana, J M
The trypanosomatids Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp. cause Chagas disease, leishmaniasis and human African trypanosomiasis, respectively. It is estimated that over 10 million people worldwide suffer from these neglected diseases, posing enormous social and economic problems in endemic areas. There are no vaccines to prevent these infections and chemotherapies are not adequate. This picture indicates that new chemotherapeutic agents must be developed to treat these illnesses. For this purpose, understanding the biology of the pathogenic trypanosomatid- host cell interface is fundamental for molecular and functional characterization of virulence factors that may be used as targets for the development of inhibitors to be used for effective chemotherapy. In this context, it is well known that proteases have crucial functions for both metabolism and infectivity of pathogens and are thus potential drug targets. In this regard, prolyl oligopeptidase and oligopeptidase B, both members of the S9 serine protease family, have been shown to play important roles in the interactions of pathogenic protozoa with their mammalian hosts and may thus be considered targets for drug design. This review aims to discuss structural and functional properties of these intriguing enzymes and their potential as targets for the development of drugs against Chagas disease, leishmaniasis and African trypanosomiasis.
Chappuis, François; Udayraj, Nitya; Stietenroth, Kai; Meussen, Ann; Bovier, Patrick A
Patients with second-stage human African trypanosomiasis treated with eflornithine (n = 251) in 2003 in Kiri, southern Sudan, had an adjusted relative risk of death of 0.2 and experienced significantly fewer cutaneous and neurological adverse effects than did patients who were treated with melarsoprol in 2001 and 2002 (n = 708).
Ilboudo, Hamidou; Camara, Oumou; Ravel, Sophie; Bucheton, Bruno; Lejon, Veerle; Camara, Mamadou; Kaboré, Jacques; Jamonneau, Vincent; Deborggraeve, Stijn
To assess the efficacy of treatment for human African trypanosomiasis, accurate tests that can discriminate relapse from cure are needed. We report the first data that the spliced leader (SL) RNA is a more specific marker for cure of human African trypanosomiasis than parasite DNA. In blood samples obtained from 61 patients in whom human African trypanosomiasis was cured, SL RNA detection had specificities of 98.4%-100%, while DNA detection had a specificity of only 77%. Data from our proof-of-concept study show that SL RNA detection has high potential as a test of cure.
Truc, P.; Jamonneau, V.; Cuny, G.; Frézil, J. L.
Stage determination of human African trypanosomiasis is based on the detection of parasites and measurements of biological changes in the cerebrospinal fluid (CSF) (concentration of white blood cells > 5 cells per mm3 and increased total protein levels). The patient is treated accordingly. Demonstration of the absence or presence of trypanosomes by the double centrifugation technique is still the only test available to clinicians for assessing treatment success. In this study, however, we evaluate the polymerase chain reaction (PCR) as a tool for assessing the disease stage of trypanosomiasis and for determining whether treatment has been successful. All 15 study patients considered to be in the advanced stage of the disease were PCR positive; however, trypanosomes were demonstrated by double centrifugation in only 11 patients. Of the five remaining patients, who were considered to be in the early stage, PCR and double centrifugation were negative. Following treatment, 13 of the 15 second-stage patients were found to be negative for the disease in at least two samples by PCR and double centrifugation. Two others were still positive by PCR immediately and one month after the treatment. Trypanosome DNA detection using PCR suggested that the two positive patients were not cured but that their possible relapse could not be identified by a search for parasites using the double centrifugation technique. Further evaluation of the PCR method is required, in particular to determine whether PCR assays could be used in studies on patients who fail to respond to melarsoprol, as observed in several foci. PMID:10534898
Kazyumba, G; Berney, M; Brighouse, G; Cruchaud, A; Lambert, P H
The relative importance of polyclonal B cell activation has been studied in relation to the development of autoantibodies in human African trypanosomiasis. In 34 patients investigated before specific treatment a broad expression of the B cell repertoire was observed including the production of anti-hapten (FITC, Penicillin, Phosphorylcholin) antibodies, of high levels of antibodies against some heterologous protein antigens (ovalbumin and tetanus toxoid) and of autoantibodies. Anti-ssDNA antibodies were detected in 84% of the patients and anti-IgG rheumatoid factors in 88%. Anti-striated muscle and anti-smooth muscle antibodies were also observed in 57 and 63% of the patients. Correlation analysis indicated that the formation of anti-DNA antibodies is associated with polyclonal B cell activation but probably depends on an additional B cell stimulation by released DNA or cross-reacting antigens. Anti-immunoglobulin antibodies are closely correlated with polyclonal B cell activation and their production is likely to reflect the high frequency of anti-IgG B cell precursors in the normal human B cell repertoire. The significance of these observations in relation to the pathological expression of trypanosomiasis should be particularly considered in the generation of immune complexes either in circulating blood or locally at the sites of parasite destruction. PMID:3491699
Lutumba, Pascal; Meheus, Filip; Robays, Jo; Miaka, Constantin; Kande, Victor; Büscher, Philippe; Dujardin, Bruno; Boelaert, Marleen
The control of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) is compromised by low sensitivity of the routinely used parasitologic confirmation tests. More sensitive alternatives, such as mini-anion exchange centrifugation technique (mAECT) or capillary tube centrifugation (CTC), are more expensive. We used formal decision analysis to assess the cost-effectiveness of alternative HAT confirmation algorithms in terms of cost per life saved. The effectiveness of the standard method, a combination of lymph node puncture (LNP), fresh blood examination (FBE), and thick blood film (TBF), was 36.8%; the LNP-FBE-CTC-mAECT sequence reached almost 80%. The cost per person examined ranged from euro1.56 for LNP-FBE-TBF to euro2.99 for LNP-TBF-CTC-mAECT-CATT (card agglutination test for trypanosomiasis) titration. LNP-TBF-CTC-mAECT was the most cost-effective in terms of cost per life saved. HAT confirmation algorithms that incorporate concentration techniques are more effective and efficient than the algorithms that are currently and routinely used by several T.b. gambiense control programs.
Keating, Joseph; Yukich, Joshua O; Sutherland, C Simone; Woods, Geordie; Tediosi, Fabrizio
The control and eventual elimination of human African trypanosomiasis (HAT) requires the expansion of current control and surveillance activities. A systematic review of the published literature on the costs of HAT prevention, treatment, and control, in addition to the economic burden, was conducted. All studies that contained primary or secondary data on costs of prevention, treatment and control were considered, resulting in the inclusion of 42 papers. The geographically focal nature of the disease and a lack of standardization in the cost data limit the usefulness of the available information for making generalizations across diverse settings. More recent information on the costs of treatment and control interventions for HAT is needed to provide accurate information for analyses and planning. The cost information contained herein can be used to inform rational decision making in control and elimination programs, and to assess potential synergies with existing vector-borne disease control programs, but programs would benefit significantly from new cost data collection.
Masand, Vijay H.; El-Sayed, Nahed N. E.; Mahajan, Devidas T.; Mercader, Andrew G.; Alafeefy, Ahmed M.; Shibi, I. G.
In the present work, sixty substituted 2-Phenylimidazopyridines previously reported with potent anti-human African trypanosomiasis (HAT) activity were selected to build genetic algorithm (GA) based QSAR models to determine the structural features that have significant correlation with the activity. Multiple QSAR models were built using easily interpretable descriptors that are directly associated with the presence or the absence of a structural scaffold, or a specific atom. All the QSAR models have been thoroughly validated according to the OECD principles. All the QSAR models are statistically very robust (R2 = 0.80-0.87) with high external predictive ability (CCCex = 0.81-0.92). The QSAR analysis reveals that the HAT activity has good correlation with the presence of five membered rings in the molecule.
Aksoy, Serap; Caccone, Adalgisa; Galvani, Alison P.; Okedi, Loyce M.
Uganda has both forms of human African trypanosomiasis (HAT): the chronic gambiense disease in the northwest and the acute rhodesiense disease in the south. The recent spread of rhodesiense into central Uganda has raised concerns given the different control strategies the two diseases require. We present knowledge on the population genetics of the major vector species Glossina fuscipes fuscipes in Uganda with a focus on population structure, measures of gene flow between populations, and the occurrence of polyandry. The microbiome composition and diversity is discussed, focusing on their potential role on trypanosome infection outcomes. We discuss the implications of these findings for large-scale tsetse control programs, including suppression or eradication, being undertaken in Uganda and potential future genetic applications. PMID:23845311
Aksoy, Serap; Caccone, Adalgisa; Galvani, Alison P; Okedi, Loyce M
Uganda has both forms of human African trypanosomiasis (HAT): the chronic gambiense disease in the northwest and the acute rhodesiense disease in the south. The recent spread of rhodesiense into central Uganda has raised concerns given the different control strategies the two diseases require. We present knowledge on the population genetics of the major vector species Glossina fuscipes fuscipes in Uganda with a focus on population structure, measures of gene flow between populations, and the occurrence of polyandry. The microbiome composition and diversity is discussed, focusing on their potential role on trypanosome infection outcomes. We discuss the implications of these findings for large-scale tsetse control programs, including suppression or eradication, being undertaken in Uganda, and potential future genetic applications.
Welburn, Susan C; Molyneux, David H; Maudlin, Ian
Epidemics of both forms of human African trypanosomiasis (HAT) are confined to spatially stable foci in Sub-Saharan Africa while tsetse distribution is widespread. Infection rates of Trypanosoma brucei gambiense in tsetse are extremely low and cannot account for the catastrophic epidemics of Gambian HAT (gHAT) seen over the past century. Here we examine the origins of gHAT epidemics and evidence implicating human genetics in HAT epidemiology. We discuss the role of stress causing breakdown of heritable tolerance in silent disease carriers generating gHAT outbreaks and see how peculiarities in the epidemiologies of gHAT and Rhodesian HAT (rHAT) impact on strategies for disease control.
Kroubi, Maya; Daulouede, Sylvie; Karembe, Hamadi; Jallouli, Youssef; Howsam, Mike; Mossalayi, Djavad; Vincendeau, Philippe; Betbeder, Didier
There is a real need to develop new therapeutic strategies for African trypanosomiasis infections. In our study, we developed a new drug delivery system of diminazene (DMZ), a trypanocidal drug registered for veterinary use. This drug candidate presents a limited efficacy, a poor affinity for brain tissue and instability. The development of colloidal formulations based on a porous cationic nanoparticle with an oily core (70DGNP + ), has potentially two advantages: stabilization of the drug and potential targeting of the parasite. We analyzed two processes of drug loading: in process (DMZ was added during the preparation of 70DGNP + at 80 °C) and post-loading (DMZ was mixed with a 70DGNP + solution at room temperature). Poor stability of the drug was observed using the in process technique. When using the post-loading technique over 80% drug entrapment efficiency was obtained at a ratio of DMZ:phospholipids (wt:wt) < 5%. Moreover, DMZ loaded into 70DGNP + was found to be protected against oxidation and was stable for at least six months at 4 °C. Finally, in vitro tests on T.b. brucei showed an increased efficacy of DMZ loaded in 70DGNP + .
Carrillo, Angela K; Guiguemde, W Armand; Guy, R Kiplin
Two of the histone deacetylases, TbDAC1 and TbDAC3, have been reported to be essential genes in trypanosomes. Therefore, we tested the activity of a panel of human histone deacetylase inhibitors (HDACi) for their ability to block proliferation of Trypanosoma brucei brucei. Among the HDACi's, the hydroxamic acid derivatives panobinostat and belinostat exhibited potency that appeared to make them viable candidates for development due to their reported pharmacokinetic characteristics. However, cellular pharmacodynamic analysis demonstrated that these drugs were unable to kill cultured parasites at exposures seen in patients at their tolerated doses and additionally failed to show any synergistic effects in combination with pentamidine, suramin, melarsoprol, or nifurtimox. Analysis of the potency of the entire HDACi panel revealed no correlations between potency against any human HDAC isoform and inhibition of T. brucei proliferation, suggesting that the trypanosome histone deacetylases possess a unique specificity. These studies confirmed that HDAC inhibitors have potential as leads against human African trypanosomiasis but that none of the current clinical candidates can be directly repurposed. Therefore, development of HDACi's with appropriate specificity and potency may be a viable route to a new class of anti-trypanosomal drugs.
Singh Grewal, Ajmer; Pandita, Deepti; Bhardwaj, Shashikant; Lather, Viney
Human African trypanosomiasis (HAT, better called as sleeping sickness), caused by two morphologically identicalprotozoan parasite Trypanosoma bruceiis transmitted by the bite of tsetse flies of Glossinagenus, mainly in the rural areas of the sub-Saharan Africa. HAT is one of the neglected tropical diseases and is characterized by sleep disturbance as the main symptom, hence is called as sleeping sickness. As it is epidemic in the poorest population of Africa, there is limited availability of safe and cost-effective tools for controlling the disease. Trypanosoma bruceigambiense causes sleeping sickness in Western and Central Africa, whereas Trypanosoma bruceirhodesiense is the reason for prevalence of sleeping sickness in Eastern and Southern Africa. For the treatment of sleeping sickness, only five drugs have been approved suramin, pentamidine, melarsoprol, eflornithine and nifurtimox. Various small molecules of diverse chemical nature have been synthesized for targeting HAT and many of them are in the clinical trialsincluding fexinidazole (phase I completed) and SCYX-7158 (advanced in phase I). The present work has been planned to review various types of small molecules developed in the last 10 years having potent antitrypanosoma activity likely to be beneficial in sleeping sickness along with different natural anti-HAT agents.
Thomas, Sarah M.; Purmal, Andrei; Pollastri, Michael; Mensa-Wilmot, Kojo
The protozoan parasite Trypanosoma brucei causes the fatal illness human African trypanosomiasis (HAT). Standard of care medications currently used to treat HAT have severe limitations, and there is a need to find new chemical entities that are active against infections of T. brucei. Following a “drug repurposing” approach, we tested anti-trypanosomal effects of carbazole-derived compounds called “Curaxins”. In vitro screening of 26 compounds revealed 22 with nanomolar potency against axenically cultured bloodstream trypanosomes. In a murine model of HAT, oral administration of compound 1 cured the disease. These studies established 1 as a lead for development of drugs against HAT. Pharmacological time-course studies revealed the primary effect of 1 to be concurrent inhibition of mitosis coupled with aberrant licensing of S-phase entry. Consequently, polyploid trypanosomes containing 8C equivalent of DNA per nucleus and three or four kinetoplasts were produced. These effects of 1 on the trypanosome are reminiscent of “mitotic slippage” or endoreplication observed in some other eukaryotes. PMID:27561392
Simarro, P P; Franco, J; Diarra, A; Postigo, J A Ruiz; Jannin, J
Despite the fact that eflornithine was considered as the safer drug to treat human African trypanosomiasis (HAT) and has been freely available since 2001, the difficulties in logistics and cost burden associated with this drug meant that the toxic melarsoprol remained the drug of choice. The World Health Organization responded to the situation by designing a medical kit containing all the materials needed to use eflornithine, and by implementing a training and drugs distribution programme which has allowed a transition to this much safer treatment. The introduction of the combination of nifurtimox and eflornithine (NECT) has accelerated the shift from melarsoprol to the best treatment available, due to reduced dosage and treatment time for eflornithine that has significantly lessened the cost and improved the burden of logistics encountered during treatment and distribution. The decrease in the use of more dangerous but cheaper melarsoprol has meant a rise in the per patient cost of treating HAT. Although NECT is cheaper than eflornithine monotherapy, an unexpected consequence has been a continuing rise in the per patient cost of treating HAT. The ethical decision of shifting to the best available treatment imposes a financial burden on HAT control programmes that might render long-term application unsustainable. These factors call for continuing research to provide new safer and more effective drugs that are simple to administer and cheaper when compared to current drugs.
Sekhar, Gayathri N; Watson, Christopher P; Fidanboylu, Mehmet; Sanderson, Lisa; Thomas, Sarah A
Human African trypanosomiasis (HAT or sleeping sickness) is a potentially fatal disease caused by the parasite, Trypanosoma brucei sp. The parasites are transmitted by the bite of insect vectors belonging to the genus Glossina (tsetse flies) and display a life cycle strategy that is equally spread between human and insect hosts. T.b. gambiense is found in western and central Africa whereas, T.b. rhodesiense is found in eastern and southern Africa. The disease has two clinical stages: a blood stage after the bite of an infected tsetse fly, followed by a central nervous system (CNS) stage where the parasite penetrates the brain; causing death if left untreated. The blood-brain barrier (BBB) makes the CNS stage difficult to treat because it prevents 98% of all known compounds from entering the brain, including some anti-HAT drugs. Those that do enter the brain are toxic compounds in their own right and have serious side effects. There are only a few drugs available to treat HAT and those that do are stage specific. This review summarizes the incidence, diagnosis, and treatment of HAT and provides a close examination of the BBB transport of anti-HAT drugs and an overview of the latest drugs in development.
Barrett, M P; Boykin, D W; Brun, R; Tidwell, R R
This review discusses the challenges of chemotherapy for human African trypanosomiasis (HAT). The few drugs registered for use against the disease are unsatisfactory for a number of reasons. HAT has two stages. In stage 1 the parasites proliferate in the haemolymphatic system. In stage 2 they invade the central nervous system and brain provoking progressive neurological dysfunction leading to symptoms that include the disrupted sleep wake patterns that give HAT its more common name of sleeping sickness. Targeting drugs to the central nervous system offers many challenges. However, it is the cost of drug development for diseases like HAT, that afflict exclusively people of the world's poorest populations, that has been the principal barrier to new drug development and has led to them becoming neglected. Here we review drugs currently registered for HAT, and also discuss the few compounds progressing through clinical trials. Finally we report on new initiatives that might allow progress to be made in developing new and satisfactory drugs for this terrible disease. PMID:17618313
Kroubi, Maya; Daulouede, Sylvie; Karembe, Hamadi; Jallouli, Youssef; Howsam, Mike; Mossalayi, Djavad; Vincendeau, Philippe; Betbeder, Didier
There is a real need to develop new therapeutic strategies for African trypanosomiasis infections. In our study, we developed a new drug delivery system of diminazene (DMZ), a trypanocidal drug registered for veterinary use. This drug candidate presents a limited efficacy, a poor affinity for brain tissue and instability. The development of colloidal formulations based on a porous cationic nanoparticle with an oily core ((70)DGNP(+)), has potentially two advantages: stabilization of the drug and potential targeting of the parasite. We analyzed two processes of drug loading: in process (DMZ was added during the preparation of (70)DGNP(+) at 80 °C) and post-loading (DMZ was mixed with a (70)DGNP(+) solution at room temperature). Poor stability of the drug was observed using the in process technique. When using the post-loading technique over 80% drug entrapment efficiency was obtained at a ratio of DMZ:phospholipids (wt:wt) < 5%. Moreover, DMZ loaded into (70)DGNP(+) was found to be protected against oxidation and was stable for at least six months at 4 °C. Finally, in vitro tests on T.b. brucei showed an increased efficacy of DMZ loaded in (70)DGNP(+).
Hayashida, Kyoko; Kajino, Kiichi; Hachaambwa, Lottie; Namangala, Boniface; Sugimoto, Chihiro
Loop-mediated isothermal amplification (LAMP) is a rapid and sensitive tool used for the diagnosis of a variety of infectious diseases. One of the advantages of this method over the polymerase chain reaction is that DNA amplification occurs at a constant temperature, usually between 60–65°C; therefore, expensive devices are unnecessary for this step. However, LAMP still requires complicated sample preparation steps and a well-equipped laboratory to produce reliable and reproducible results, which limits its use in resource-poor laboratories in most developing countries. In this study, we made several substantial modifications to the technique to carry out on-site diagnosis of Human African Trypanosomiasis (HAT) in remote areas using LAMP. The first essential improvement was that LAMP reagents were dried and stabilized in a single tube by incorporating trehalose as a cryoprotectant to prolong shelf life at ambient temperature. The second technical improvement was achieved by simplifying the sample preparation step so that DNA or RNA could be amplified directly from detergent-lysed blood samples. With these modifications, diagnosis of HAT in local clinics or villages in endemic areas becomes a reality, which could greatly impact on the application of diagnosis not only for HAT but also for other tropical diseases. PMID:25769046
Nzou, Samson Muuo; Fujii, Yoshito; Miura, Masashi; Mwau, Matilu; Mwangi, Anne Wanjiru; Itoh, Makoto; Salam, Md Abdus; Hamano, Shinjiro; Hirayama, Kenji; Kaneko, Satoshi
Human African trypanosomiasis (HAT) is a disease caused by Kinetoplastid infection. Serological tests are useful for epidemiological surveillance. The aim of this study was to develop a multiplex serological assay for HAT to assess the diagnostic value of selected HAT antigens for sero-epidemiological surveillance. We cloned loci encoding eight antigens from Trypanosoma brucei gambiense, expressed the genes in bacterial systems, and purified the resulting proteins. Antigens were subjected to Luminex multiplex assays using sera from HAT and VL patients to assess the antigens' immunodiagnostic potential. Among T. b. gambiense antigens, the 64-kDa and 65-kDa invariant surface glycoproteins (ISGs) and flagellar calcium binding protein (FCaBP) had high sensitivity for sera from T. b. gambiense patients, yielding AUC values of 0.871, 0.737 and 0.858 respectively in receiver operating characteristics (ROC) analysis. The ISG64, ISG65, and FCaBP antigens were partially cross-reactive to sera from Trypanosoma brucei rhodesiense patients. The GM6 antigen was cross-reactive to sera from T. b. rhodesiense patients as well as to sera from VL patients. Furthermore, heterogeneous antibody responses to each individual HAT antigen were observed. Testing for multiple HAT antigens in the same panel allowed specific and sensitive detection. Our results demonstrate the utility of applying multiplex assays for development and evaluation of HAT antigens for use in sero-epidemiological surveillance.
Franco, J R; Simarro, P P; Diarra, A; Ruiz-Postigo, J A; Jannin, J G
Considering the epidemic situation of gambiense human African trypanosomiasis (HAT) at the end of the twentieth century, the World Health Organization (WHO) and partners strengthened disease control and surveillance. Over the last 15 years, the activities implemented through the National Control Programmes have brought gambiense HAT under control and now its elimination is deemed as an achievable goal. In 2012, WHO targeted gambiense HAT for elimination as a public health problem by 2020. The final goal will be the sustainable disease elimination by 2030, defined as the interruption of the transmission of gambiense HAT. The elimination is considered feasible, because of the epidemiological vulnerability of the disease, the current state of control, the availability of strategies and tools and international commitment and political will. Integration of activities in the health system is needed to ensure the sustainability of the elimination. The development of user-friendly diagnostic and treatment tools will facilitate the integration process. Adequate funding is needed to implement activities, but also to support research that will make the elimination sustainable. A long-term commitment by donors is needed and ownership of the process by endemic countries is critical.
For over fifty years, human African trypanosomiasis (HAT, sleeping sickness) has been treated with suramin, pentamidine and the very toxic organo-arsenical melarsoprol that was the only drug available for effective treatment of the second stage of the disease. Recently there have been significant efforts using molecular and biochemical approaches to drug design, including high-throughput screening, but the number of lead compounds with promising activity against T. brucei spp. and an acceptable toxicity index has remained astonishingly small. Clinical research continues to be difficult due to the economic constraints and the complexity of trials on a low prevalence disease in remote and impoverished African regions. Despite those limitations the situation for the patients is improving thanks to the combination of a number of critical factors. By the late 1990s the disease had reached epidemic levels that triggered political support. WHO would sign a donation agreement with the manufacturers for all drugs to treat HAT. A result of this agreement was that eflornithine which is much safer than melarsoprol became available and widely used by non-governmental organizations. The Impamel I and II programmes demonstrated that against all odds the conduct of clinical trials on HAT was feasible. This allowed the initiation of trials on combination therapies which eventually resulted in the nifurtimox-eflornithine combination treatment (NECT). This combination is currently being introduced as first line treatment, and there is even the prospect of having a new compound, fexinidazole, in the development pipeline. This review summarizes the key information about the existing drugs and gives a comprehensive summary about the recent and currently ongoing efforts towards new drugs.
Tiberti, Natalia; Hainard, Alexandre; Lejon, Veerle; Robin, Xavier; Ngoyi, Dieudonné Mumba; Turck, Natacha; Matovu, Enock; Enyaru, John; Ndung'u, Joseph Mathu; Scherl, Alexander; Dayon, Loïc; Sanchez, Jean-Charles
Human African trypanosomiasis, or sleeping sickness, is a parasitic disease endemic in sub-Saharan Africa, transmitted to humans through the bite of a tsetse fly. The first or hemolymphatic stage of the disease is associated with presence of parasites in the bloodstream, lymphatic system, and body tissues. If patients are left untreated, parasites cross the blood-brain barrier and invade the cerebrospinal fluid and the brain parenchyma, giving rise to the second or meningoencephalitic stage. Stage determination is a crucial step in guiding the choice of treatment, as drugs used for S2 are potentially dangerous. Current staging methods, based on counting white blood cells and demonstrating trypanosomes in cerebrospinal fluid, lack specificity and/or sensitivity. In the present study, we used several proteomic strategies to discover new markers with potential for staging human African trypanosomiasis. Cerebrospinal fluid (CSF) samples were collected from patients infected with Trypanosoma brucei gambiense in the Democratic Republic of Congo. The stage was determined following the guidelines of the national control program. The proteome of the samples was analyzed by two-dimensional gel electrophoresis (n = 9), and by sixplex tandem mass tag (TMT) isobaric labeling (n = 6) quantitative mass spectrometry. Overall, 73 proteins were overexpressed in patients presenting the second stage of the disease. Two of these, osteopontin and β-2-microglobulin, were confirmed to be potential markers for staging human African trypanosomiasis (HAT) by Western blot and ELISA. The two proteins significantly discriminated between S1 and S2 patients with high sensitivity (68% and 78%, respectively) for 100% specificity, and a combination of both improved the sensitivity to 91%. The levels of osteopontin and β-2-microglobulin in CSF of S2 patients (μg/ml range), as well as the fold increased concentration in S2 compared with S1 (3.8 and 5.5 respectively) make the two markers good
Borowy, N K; Schell, D; Schäfer, C; Overath, P
A sensitive diagnostic assay for parasitic infections based on the detection of anti-enzyme antibodies is presented. All serum antibodies produced in response to parasite antigens are immobilized via their Fc domain on matrix-bound protein G. Incubation of the immobilized antibodies with saturating amounts of parasite extract results in the binding of all recognized antigens, including those directed against a specific and readily measurable enzyme. The amount of bound enzyme is proportional to the anti-enzyme antibody concentration in the serum. The application of this principle is demonstrated for the diagnosis of both human African trypanosomiasis and visceral leishmaniasis by the detection of antibodies against parasite acid phosphatases.
Rodgers, Jean; Jones, Amy; Gibaud, Stéphane; Bradley, Barbara; McCabe, Christopher; Barrett, Michael P; Gettinby, George; Kennedy, Peter G E
Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites Trypanosoma brucei (T. b.) gambiense or T. b. rhodesiense and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage T. b. rhodesiense infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-β-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties in vitro and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy.
Ojo, Kayode K; Gillespie, J Robert; Riechers, Aaron J; Napuli, Alberto J; Verlinde, Christophe L M J; Buckner, Frederick S; Gelb, Michael H; Domostoj, Mathias M; Wells, Susan J; Scheer, Alexander; Wells, Timothy N C; Van Voorhis, Wesley C
Development of a safe, effective, and inexpensive therapy for African trypanosomiasis is an urgent priority. In this study, we evaluated the validity of Trypanosoma brucei glycogen synthase kinase 3 (GSK-3) as a potential drug target. Interference with the RNA of either of two GSK-3 homologues in bloodstream-form T. brucei parasites led to growth arrest and altered parasite morphology, demonstrating their requirement for cell survival. Since the growth arrest after RNA interference appeared to be more profound for T. brucei GSK-3 "short" (Tb10.161.3140) than for T. brucei GSK-3 "long" (Tb927.7.2420), we focused on T. brucei GSK-3 short for further studies. T. brucei GSK-3 short with an N-terminal maltose-binding protein fusion was cloned, expressed, and purified in a functional form. The potency of a GSK-3-focused inhibitor library against the recombinant enzyme of T. brucei GSK-3 short, as well as bloodstream-form parasites, was evaluated with the aim of determining if compounds that inhibit enzyme activity could also block the parasites' growth and proliferation. Among the compounds active against the cell, there was an excellent correlation between activity inhibiting the T. brucei GSK-3 short enzyme and the inhibition of T. brucei growth. Thus, there is reasonable genetic and chemical validation of GSK-3 short as a drug target for T. brucei. Finally, selective inhibition may be required for therapy targeting the GSK-3 enzyme, and a molecular model of the T. brucei GSK-3 short enzyme suggests that compounds that selectively inhibit T. brucei GSK-3 short over the human GSK-3 enzymes can be found.
Vincent, Isabel M.; Daly, Rónán; Courtioux, Bertrand; Cattanach, Amy M.; Biéler, Sylvain; Ndung’u, Joseph M.; Bisser, Sylvie; Barrett, Michael P.
Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan) showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of “sleeping sickness”. Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity) and stage of disease (92% sensitivity and 81% specificity). A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages) versus control. PMID:27941966
Sutherland, C. Simone; Yukich, Joshua; Goeree, Ron; Tediosi, Fabrizio
Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and
Patrick, Donald A; Gillespie, J Robert; McQueen, Joshua; Hulverson, Matthew A; Ranade, Ranae M; Creason, Sharon A; Herbst, Zackary M; Gelb, Michael H; Buckner, Frederick S; Tidwell, Richard R
A previous publication from this lab (Patrick, et al. Bioorg. Med. Chem. 2016, 24 , 2451 - 2465 ) explored the antitrypanosomal activities of novel derivatives of 2-(2-benzamido)ethyl-4-phenylthiazole (1), which had been identified as a hit against Trypanosoma brucei, the causative agent of human African trypanosomiasis. While a number of these compounds, particularly the urea analogues, were quite potent, these molecules as a whole exhibited poor metabolic stability. The present work describes the synthesis of 65 new analogues arising from medicinal chemistry optimization at different sites on the molecule. The most promising compounds were the urea derivatives of 2-aryl-benzothiazol-5-amines. One such analogue, (S)-2-(3,4-difluorophenyl)-5-(3-fluoro-N-pyrrolidylamido)benzothiazole (57) was chosen for in vivo efficacy studies based upon in vitro activity, metabolic stability, and brain penetration. This compound attained 5/5 cures in murine models of both early and late stage human African trypanosomiasis, representing a new lead for the development of drugs to combat this neglected disease.
Biéler, Sylvain; Waltenberger, Harald; Barrett, Michael P.; McCulloch, Richard; Mottram, Jeremy C.; Carrington, Mark; Schwaeble, Wilhelm; McKerrow, James; Phillips, Margaret A.; Michels, Paul A.; Büscher, Philippe; Sanchez, Jean-Charles; Bishop, Richard; Robinson, Derrick R.; Bangs, James; Ferguson, Michael; Nerima, Barbara; Albertini, Audrey; Michel, Gerd; Radwandska, Magdalena; Ndung’u, Joseph Mathu
Background Control and elimination of human African trypanosomiasis (HAT) can be accelerated through the use of diagnostic tests that are more accurate and easier to deploy. The goal of this work was to evaluate the immuno-reactivity of antigens and identify candidates to be considered for development of a simple serological test for the detection of Trypanosoma brucei gambiense or T. b. rhodesiense infections, ideally both. Methodology/Principal Findings The reactivity of 35 antigens was independently evaluated by slot blot and ELISA against sera from both T. b. gambiense and T. b. rhodesiense infected patients and controls. The antigens that were most reactive by both tests to T. b. gambiense sera were the membrane proteins VSG LiTat 1.3, VSG LiTat 1.5 and ISG64. Reactivity to T. b. rhodesiense sera was highest with VSG LiTat 1.3, VSG LiTat 1.5 and SRA, although much lower than with T. b. gambiense samples. The reactivity of all possible combinations of antigens was also calculated. When the slot blot results of 2 antigens were paired, a VSG LiTat 1.3- ISG75 combination performed best on T. b. gambiense sera, while a VSG LiTat 1.3-VSG LiTat 1.5 combination was the most reactive using ELISA. A combination of SRA and either VSG LiTat 1.3 or VSG LiTat 1.5 had the highest reactivity on T. b. rhodesiense sera according to slot blot, while in ELISA, pairing SRA with either GM6 or VSG LiTat 1.3 yielded the best results. Conclusions This study identified antigens that were highly reactive to T. b. gambiense sera, which could be considered for developing a serological test for gambiense HAT, either individually or in combination. Antigens with potential for inclusion in a test for T. b. rhodesiense HAT were also identified, but because their reactivity was comparatively lower, a search for additional antigens would be required before developing a test for this form of the disease. PMID:27936225
Lejon, Veerle; Mumba Ngoyi, Dieudonné; Kestens, Luc; Boel, Luc; Barbé, Barbara; Kande Betu, Victor; van Griensven, Johan; Bottieau, Emmanuel; Muyembe Tamfum, Jean-Jacques; Jacobs, Jan; Büscher, Philippe
In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and
Kaur, Raminder; Gupta, V K; Dhariwal, A C; Jain, D C; Shiv, Lal
Human Trypanosomiasis is a rare occurrence in India. In the cases reported so far the disease causative species have been the species infective to animals viz., Trypanosoma lewisi and Trypanosoma evansi. These animal species usually non pathogenic in humans can acquire the desired virulence and emerge as human pathogens causing serious disease, in the right combination of environmental, host related and organism related factors. We report here a case of trypanosomiasis caused by the rodent parasite T. lewisi in a two months old infant in urban Mumbai. Under the fastly changing environmental scenario there is an urgent need to be prepared for the emerging zoonoses. Any unusual disease occurrence in a given geographical area acquires a special significance in this context and should be reported to assess its public health importance and be prepared to deal with the consequent challenges posed, if any.
Batchelor, Nicola A; Atkinson, Peter M; Gething, Peter W; Picozzi, Kim; Fèvre, Eric M; Kakembo, Abbas S L; Welburn, Susan C
The continued northwards spread of Rhodesian sleeping sickness or Human African Trypanosomiasis (HAT) within Uganda is raising concerns of overlap with the Gambian form of the disease. Disease convergence would result in compromised diagnosis and treatment for HAT. Spatial determinants for HAT are poorly understood across small areas. This study examines the relationships between Rhodesian HAT and several environmental, climatic and social factors in two newly affected districts, Kaberamaido and Dokolo. A one-step logistic regression analysis of HAT prevalence and a two-step logistic regression method permitted separate analysis of both HAT occurrence and HAT prevalence. Both the occurrence and prevalence of HAT were negatively correlated with distance to the closest livestock market in all models. The significance of distance to the closest livestock market strongly indicates that HAT may have been introduced to this previously unaffected area via the movement of infected, untreated livestock from endemic areas. This illustrates the importance of the animal reservoir in disease transmission, and highlights the need for trypanosomiasis control in livestock and the stringent implementation of regulations requiring the treatment of cattle prior to sale at livestock markets to prevent any further spread of Rhodesian HAT within Uganda.
Rodgers, Jean; Bradley, Barbara; Kennedy, Peter G E
Drug therapy for late-stage (encephalitic) human African trypanosomiasis (HAT) is currently very unsatisfactory with the most commonly used drug, melarsoprol, having a 5% overall mortality. There is evidence in a mouse model of HAT that Substance P (SP) receptor antagonism reduces the neuroinflammatory reaction to CNS trypanosome infection. In this study we investigated the effects of combination chemotherapy with melarsoprol and a humanised SP receptor antagonist aprepitant (EMEND) in this mouse model. The melarsoprol/aprepitant drug combination did not produce any clinical signs of illness in mice with CNS trypanosome infection. This lack of any additional or unexpected CNS toxicity in the mouse model of CNS HAT provides valuable safety data for the future possible use of this drug combination in patients with late-stage HAT.
Raghavan, Ram K; Saunders, Ashley B; Goodin, Doug G; Anderson, Gary A; Harkin, Kenneth R
American trypanosomiasis or Chagas disease caused by Trypanosoma cruzi affects many mammals, including humans and dogs, in all Latin American countries outside the Caribbean and increasingly also in the southern United States. Dogs are considered as reliable sentinels and have been identified as an important risk factor for the disease in humans in endemic countries. Factors that determine American trypanosomiasis in dogs may therefore have public health relevance. Associations of different environmental, locational, and pet owner socioeconomic conditions were evaluated retrospectively as potential risk factors for American trypanosomiasis status in dogs in a case-control study. Laboratory-confirmed cases received at the Texas A&M University Veterinary Medical Teaching Hospital between the years 2000 and 2012 and candidate risk factor variables extracted from publicly available environmental data and 2010 US Census Bureau were used. The sample included 42 dogs serologically positive and 82 dogs serologically negative determined by indirect immunofluorescent assay. The diagnostic titer was 1:160 (case). Univariate logistic regressions followed by stepwise multivariate logistic modeling were used for variable screening and to determine the strengths of variable associations with case status. Total Edge Contrast Index (odds ratio [OR] = 3.35, 95% confidence interval [CI] 3.10, 3.62), residing in homes that had rural addresses (OR = 2.48, 95% CI 2.43, 2.53), total number of owner occupied housing units in a neighborhood with a householder who is Hispanic or Latino (OR = 1.66, 95% CI 1.04, 2.66), and the total number of housing units in a neighborhood that were built on or prior to year 1980 (OR = 2.22, 95% CI 1.94, 2.55) were identified as risk factors. Suitable awareness campaigns and future research that considers pet owner housing and socioeconomic circumstances are necessary for effective prevention and control of this disease among dogs.
Cordon-Obras, Carlos; Rodriguez, Yasmin Fermin; Fernandez-Martinez, Amalia; Cano, Jorge; Ndong-Mabale, Nicolas; Ncogo-Ada, Policarpo; Ndongo-Asumu, Pedro; Aparicio, Pilar; Navarro, Miguel; Benito, Agustin; Bart, Jean-Mathieu
Gambiense trypanosomiasis is considered an anthroponotic disease. Consequently, control programs are generally aimed at stopping transmission of Trypanosoma brucei gambiense (T. b. gambiense) by detecting and treating human cases. However, the persistence of numerous foci despite efforts to eliminate this disease questions this strategy as unique tool to pursue the eradication. The role of animals as a reservoir of T. b. gambiense is still controversial, but could partly explain maintenance of the infection at hypo-endemic levels. In the present study, we evaluated the presence of T. b. gambiense in wild animals in Equatorial Guinea. The infection rate ranged from 0.8% in the insular focus of Luba to more than 12% in Mbini, a focus with a constant trickle of human cases. The parasite was detected in a wide range of animal species including four species never described previously as putative reservoirs. Our study comes to reinforce the hypothesis that animals may play a role in the persistence of T. b. gambiense transmission, being particularly relevant in low transmission settings. Under these conditions the integration of sustained vector control and medical interventions should be considered to achieve the elimination of gambiense trypanosomiasis. PMID:26257727
Joshi, P P; Chaudhari, A; Shegokar, V R; Powar, R M; Dani, V S; Somalwar, A M; Jannin, J; Truc, P
The first reported human case of trypanosomiasis caused by Trypanosoma evansi was treated using suramin. Patient follow-up indicates that the drug and specific regimen used were well tolerated. Clinical, serological and parasitological investigations at 6 months indicate complete cure of the patient. Suramin should be considered in the treatment of other cases of human T. evansi infection, if they occur.
Glycogen synthase kinase 3 (GSK3) is a genetically validated drug target for human African trypanosomiasis (HAT), also called African sleeping sickness. We report the synthesis and biological evaluation of aminopyrazole derivatives as Trypanosoma brucei GSK3 short inhibitors. Low nanomolar inhibitors, which had high selectivity over the off-target human CDK2 and good selectivity over human GSK3β enzyme, have been prepared. These potent kinase inhibitors demonstrated low micromolar levels of inhibition of the Trypanosoma brucei brucei parasite grown in culture. PMID:25198388
National and international efforts to eradicate tsetse fly-borne human and animal trypanosomiasis are critically evaluated, and possible reasons for their failure in many cases are discussed. Some formerly performed campaigns in specific areas with positive results cannot be taken as examples to solve the main problems. In future, a significant reduction of trypanosomiasis cases will be possible to achieve only if a concerted long-term Pan-African approach, based on financial security, the continuity of expert staff, and a well-planned, ecologically sound land use, is generally accepted.
Kerry, Louise E.; Pegg, Elaine E.; Cameron, Donald P.; Budzak, James; Poortinga, Gretchen; Hannan, Katherine M.; Hannan, Ross D.
Trypanosoma brucei relies on an essential Variant Surface Glycoprotein (VSG) coat for survival in the mammalian bloodstream. High VSG expression within an expression site body (ESB) is mediated by RNA polymerase I (Pol I), which in other eukaryotes exclusively transcribes ribosomal RNA genes (rDNA). As T. brucei is reliant on Pol I for VSG transcription, we investigated Pol I transcription inhibitors for selective anti-trypanosomal activity. The Pol I inhibitors quarfloxin (CX-3543), CX-5461, and BMH-21 are currently under investigation for treating cancer, as rapidly dividing cancer cells are particularly dependent on high levels of Pol I transcription compared with nontransformed cells. In T. brucei all three Pol I inhibitors have IC50 concentrations for cell proliferation in the nanomolar range: quarfloxin (155 nM), CX-5461 (279 nM) or BMH-21 (134 nM) compared with IC50 concentrations in the MCF10A human breast epithelial cell line (4.44 μM, 6.89 μM or 460 nM, respectively). T. brucei was therefore 29-fold more sensitive to quarfloxin, 25-fold more sensitive to CX-5461 and 3.4-fold more sensitive to BMH-21. Cell death in T. brucei was due to rapid inhibition of Pol I transcription, as within 15 minutes treatment with the inhibitors rRNA precursor transcript was reduced 97-98% and VSG precursor transcript 91-94%. Incubation with Pol I transcription inhibitors also resulted in disintegration of the ESB as well as the nucleolus subnuclear structures, within one hour. Rapid ESB loss following the block in Pol I transcription argues that the ESB is a Pol I transcription nucleated structure, similar to the nucleolus. In addition to providing insight into Pol I transcription and ES control, Pol I transcription inhibitors potentially also provide new approaches to treat trypanosomiasis. PMID:28263991
Kerry, Louise E; Pegg, Elaine E; Cameron, Donald P; Budzak, James; Poortinga, Gretchen; Hannan, Kate; Hannan, Ross D; Rudenko, Gloria
Trypanosoma brucei relies on an essential Variant Surface Glycoprotein (VSG) coat for survival in the mammalian bloodstream. High VSG expression within an expression site body (ESB) is mediated by RNA polymerase I (Pol I), which in other eukaryotes exclusively transcribes ribosomal RNA genes (rDNA). As T. brucei is reliant on Pol I for VSG transcription, we investigated Pol I transcription inhibitors for selective anti-trypanosomal activity. The Pol I inhibitors quarfloxin (CX-3543), CX-5461, and BMH-21 are currently under investigation for treating cancer, as rapidly dividing cancer cells are particularly dependent on high levels of Pol I transcription compared with nontransformed cells. In T. brucei all three Pol I inhibitors have IC50 concentrations for cell proliferation in the nanomolar range: quarfloxin (155 nM), CX-5461 (279 nM) or BMH-21 (134 nM) compared with IC50 concentrations in the MCF10A human breast epithelial cell line (4.44 μM, 6.89 μM or 460 nM, respectively). T. brucei was therefore 29-fold more sensitive to quarfloxin, 25-fold more sensitive to CX-5461 and 3.4-fold more sensitive to BMH-21. Cell death in T. brucei was due to rapid inhibition of Pol I transcription, as within 15 minutes treatment with the inhibitors rRNA precursor transcript was reduced 97-98% and VSG precursor transcript 91-94%. Incubation with Pol I transcription inhibitors also resulted in disintegration of the ESB as well as the nucleolus subnuclear structures, within one hour. Rapid ESB loss following the block in Pol I transcription argues that the ESB is a Pol I transcription nucleated structure, similar to the nucleolus. In addition to providing insight into Pol I transcription and ES control, Pol I transcription inhibitors potentially also provide new approaches to treat trypanosomiasis.
Behera, Ranjan; Thomas, Sarah M.
Human African trypanosomiasis (HAT) is caused by the protozoan Trypanosoma brucei. New drugs are needed to treat HAT because of undesirable side effects and difficulties in the administration of the antiquated drugs that are currently used. In human proliferative diseases, protein tyrosine kinase (PTK) inhibitors (PTKIs) have been developed into drugs (e.g., lapatinib and erlotinib) by optimization of a 4-anilinoquinazoline scaffold. Two sets of facts raise a possibility that drugs targeted against human PTKs could be “hits” for antitrypanosomal lead discoveries. First, trypanosome protein kinases bind some drugs, namely, lapatinib, CI-1033, and AEE788. Second, the pan-PTK inhibitor tyrphostin A47 blocks the endocytosis of transferrin and inhibits trypanosome replication. Following up on these concepts, we performed a focused screen of various PTKI drugs as possible antitrypanosomal hits. Lapatinib, CI-1033, erlotinib, axitinib, sunitinib, PKI-166, and AEE788 inhibited the replication of bloodstream T. brucei, with a 50% growth inhibitory concentration (GI50) between 1.3 μM and 2.5 μM. Imatinib had no effect (i.e., GI50 > 10 μM). To discover leads among the drugs, a mouse model of HAT was used in a proof-of-concept study. Orally administered lapatinib reduced parasitemia, extended the survival of all treated mice, and cured the trypanosomal infection in 25% of the mice. CI-1033 and AEE788 reduced parasitemia and extended the survival of the infected mice. On the strength of these data and noting their oral bioavailabilities, we propose that the 4-anilinoquinazoline and pyrrolopyrimidine scaffolds of lapatinib, CI-1033, and AEE788 are worth optimizing against T. brucei in medicinal chemistry campaigns (i.e., scaffold repurposing) to discover new drugs against HAT. PMID:24468788
Behera, Ranjan; Thomas, Sarah M; Mensa-Wilmot, Kojo
Human African trypanosomiasis (HAT) is caused by the protozoan Trypanosoma brucei. New drugs are needed to treat HAT because of undesirable side effects and difficulties in the administration of the antiquated drugs that are currently used. In human proliferative diseases, protein tyrosine kinase (PTK) inhibitors (PTKIs) have been developed into drugs (e.g., lapatinib and erlotinib) by optimization of a 4-anilinoquinazoline scaffold. Two sets of facts raise a possibility that drugs targeted against human PTKs could be "hits" for antitrypanosomal lead discoveries. First, trypanosome protein kinases bind some drugs, namely, lapatinib, CI-1033, and AEE788. Second, the pan-PTK inhibitor tyrphostin A47 blocks the endocytosis of transferrin and inhibits trypanosome replication. Following up on these concepts, we performed a focused screen of various PTKI drugs as possible antitrypanosomal hits. Lapatinib, CI-1033, erlotinib, axitinib, sunitinib, PKI-166, and AEE788 inhibited the replication of bloodstream T. brucei, with a 50% growth inhibitory concentration (GI50) between 1.3 μM and 2.5 μM. Imatinib had no effect (i.e., GI50>10 μM). To discover leads among the drugs, a mouse model of HAT was used in a proof-of-concept study. Orally administered lapatinib reduced parasitemia, extended the survival of all treated mice, and cured the trypanosomal infection in 25% of the mice. CI-1033 and AEE788 reduced parasitemia and extended the survival of the infected mice. On the strength of these data and noting their oral bioavailabilities, we propose that the 4-anilinoquinazoline and pyrrolopyrimidine scaffolds of lapatinib, CI-1033, and AEE788 are worth optimizing against T. brucei in medicinal chemistry campaigns (i.e., scaffold repurposing) to discover new drugs against HAT.
Balasegaram, Manica; Harris, Steve; Checchi, Francesco; Hamel, Catherine; Karunakara, Unni
OBJECTIVE: In 2002-03, the Republic of the Congo increased the threshold separating stage 1 and 2 cases of human African trypanosomiasis (HAT) from a cerebrospinal fluid (CSF) white cell count of 5 cells/mm(3) to 10 cells/mm(3). We aimed to assess whether the increased threshold of 10 cells/mm(3) is a safe indicator of stage 2 disease. METHODS: We assessed patients treated for stage 1 HAT caused by Trypanosoma brucei gambiense in the Republic of the Congo between April 2001 and April 2005. Patients with 0-10 cells/mm(3) in CSF were classed as stage 1 and treated with pentamidine. Patients with CSF of > 10 cells/mm(3) were classed as stage 2 and treated with either melarsoprol or eflornithine. We did a retrospective analysis of all patients treated after the September 2002 increase in threshold for classification of HAT disease stage 2, and who were eligible for at least 1 year of follow-up. Primary outcome was survival without death or relapse within 1 year of discharge. Risk factors for treatment failure, in particular CSF white cell count on diagnosis, were assessed. FINDINGS: Between September 2002 to April 2004, 692 patients eligible for our analysis were treated with pentamidine. All were discharged alive. Relapse rate was 5% (n = 33). The only identified risk factor for relapse was a CSF white cell count of 6-10 cells/mm(3) rather than 0-5 cells/mm(3) (adjusted hazard ratio 3.27 (95% confidence interval, 1.52-7.01); P = 0.002). CONCLUSION: A threshold of 5 white cells/mm(3) in CSF is safer than 10 cells/mm(3) to determine stage 2 HAT and reduce risk of relapse. PMID:17128357
El-Bahnasawy, Mamdouh M M; Khater, Mai Kh A; Morsy, Tosson A
Trypanosomes (including humans) are blood and sometimes tissue parasites of the order Kinetoplastida, family Trypanosomatidae, genus Trypanosoma, principally transmitted by biting insects where most of them undergo a biological cycle. They are divided into Stercoraria with the posterior station inoculation, including T. cruzi, both an extra- and intracellular parasite that causes Chagas disease, a major human disease affecting 15 million people and threatening 100 million people in Latin America, and the Salivaria with the anterior station inoculation, mainly African livestock pathogenic trypanosomes, including the agents of sleeping sickness, a major human disease affecting around half a million people and threatening 60 million people in Africa. Now, T. evansi was reported in man is it required to investigate its zoonotic potential?
Palmer, Jennifer J.; Surur, Elizeous I.; Checchi, Francesco; Ahmad, Fayaz; Ackom, Franklin Kweku; Whitty, Christopher J. M.
Background Active screening by mobile teams is considered the most effective method for detecting gambiense-type human African trypanosomiasis (HAT) but constrained funding in many post-conflict countries limits this approach. Non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases for testing based on symptoms. We tested a training intervention for HCWs in peripheral facilities in Nimule, South Sudan to increase knowledge of HAT symptomatology and the rate of syndromic referrals to a central screening and treatment centre. Methodology/Principal Findings We trained 108 HCWs from 61/74 of the public, private and military peripheral health facilities in the county during six one-day workshops and assessed behaviour change using quantitative and qualitative methods. In four months prior to training, only 2/562 people passively screened for HAT were referred from a peripheral HCW (0 cases detected) compared to 13/352 (2 cases detected) in the four months after, a 6.5-fold increase in the referral rate observed by the hospital. Modest increases in absolute referrals received, however, concealed higher levels of referral activity in the periphery. HCWs in 71.4% of facilities followed-up had made referrals, incorporating new and pre-existing ideas about HAT case detection into referral practice. HCW knowledge scores of HAT symptoms improved across all demographic sub-groups. Of 71 HAT referrals made, two-thirds were from new referrers. Only 11 patients completed the referral, largely because of difficulties patients in remote areas faced accessing transportation. Conclusions/Significance The training increased knowledge and this led to more widespread appropriate HAT referrals from a low base. Many referrals were not completed, however. Increasing access to screening and/or diagnostic tests in the periphery will be needed for greater impact on case-detection in this context. These data suggest it may be
unlimited 13. SUPPLEMENTARY NOTES See also ADA545141. Chapter 2 from e-book, Topics on the Pathology of Protozoan and Invasive Arthropod Diseases. 14...rod-shaped kinetoplast (arrow). x1000 2 2 • Topics on The paThology of proTozoan and invasive arThropod diseases In South America, trypanosomiasis...endemic areas.6,7 Trypanosoma rangeli, a related and similarly distributed protozoan , is nonpathogenic. It does not invade and destroy cells and
Devine, William G; Diaz-Gonzalez, Rosario; Ceballos-Perez, Gloria; Rojas, Domingo; Satoh, Takashi; Tear, Westley; Ranade, Ranae M; Barros-Álvarez, Ximena; Hol, Wim G J; Buckner, Frederick S; Navarro, Miguel; Pollastri, Michael P
Human African trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-indol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from a high-throughput screen of >42,000 compounds as a highly potent and fast-acting trypanocidal agent capable of curing a bloodstream infection of Trypanosoma brucei in mice. We have designed a library of analogues to probe the structure-activity relationship and improve the predicted central nervous system (CNS) exposure of NEU-1053. We report the activity of these inhibitors of T. brucei, the efficacy of NEU-1053 in a murine CNS model of infection, and identification of the target of NEU-1053 via X-ray crystallography.
Farikou, Oumarou; Njiokou, Flobert; Mbida Mbida, Jean A; Njitchouang, Guy R; Djeunga, Hugues Nana; Asonganyi, Tazoacha; Simarro, Pere P; Cuny, Gérard; Geiger, Anne
Epidemiological surveys were conducted in two historical human African trypanosomiasis foci in South Cameroon, Bipindi and Campo. In each focus, three sampling areas were defined. In Bipindi, only Glossina palpalis was identified, whereas four species were identified in Campo, G. palpalis being highly predominant (93%). For further analyses, 75 flies were randomly chosen among the flies trapped in each of the six villages. Large and statistically significant differences were recorded between both (1) the prevalence of Sodalis glossinidius (tsetse symbiont) and the prevalence of trypanosome infection of the major fly species G. p. palpalis and (2) the respective prevalence of symbiont and infection between the two foci. Despite these differences, the rate of infected flies harbouring the symbiont was very similar (75%) in both foci, suggesting that symbionts favour fly infection by trypanosomes. This hypothesis was statistically tested and assessed, showing that S. glossinidius is potentially an efficient target for controlling tsetse fly vectorial competence and consequently sleeping sickness.
Al I1.V I 11NMrN? I I PNSr L Cr-\\’olLl~itwlIud thiomhocytes w* re ofnpji ,i ini 1. (:onFlrlFCP!k n--r-l Ii. r,. vu~jt- thrombocyte survival ", uri l 1 3...above. The inoculated cultures were incubated at 260 C and examined daily for the presence of promastigotes by ordinary light microscopy . Promasti...a glass microscope slide. A thick smear was made and stained with Field’s stain and subsequently examined by light microscopy . Culture Procedures Com
specific antitrypanosomal antibodies develop i-. It is hypothesized that this situation leads to periods of antigen excess and it is probable that...circulating antigen- antibody complexes are formed. Early studies with Rhesus monkeys infected with Trypanosoma rhodesiense (Strain 1886) indicated... antibody . We are now in the process of setting up an experiment in which we will first attempt to elute off the an’ibodies with glycine-HCl buffer (pH 3.2
by the Biuret method and serum electrophoresis on cellulose acetate was done using the BecKman Microzone technique. Immunoglobulin levels were...1:8 4 4 4 3 3 2 2 2 1:16 4 4 3 2 Tr* Tr Tr Tr 1:32 4 3 2 Tr Tr Tr Tr Tr 1:64 1 Tr Tr Tr - - * Trace reaction STAGE 1: 1. Patient’s serum added in
Gehrig, Stefanie; Efferth, Thomas
Human African trypanosomiasis is an infectious disease which has resulted in the deaths of thousands of people in Sub-Saharan Africa. Two subspecies of the protozoan parasite Trypanosoma brucei are the causative agents of the infection, whereby T. b. gambiense leads to chronic development of the disease and T. b. rhodesiense establishes an acute form, which is fatal within months or even weeks. Current chemotherapy treatment is complex, since special drugs have to be used for the different development stages of the disease, as well as for the parasite concerned. Melarsoprol is the only approved drug for effectively treating both subspecies of human African trypanosomiasis in its advanced stage, however, the drug's potency is constrained due to an unacceptable side effect: encephalopathy, which develops in one out of every 20 patients who are treated with the drug. In addition to the deleterious treatment with melarsoprol, the number of drug-resistant strains of T. brucei supp. increases. Mechanisms of drug resistance have been elucidated and involve decreased drug import through the loss of the purine transporter P2 as well as enhanced drug export, mediated by a multidrug resistance-associated protein called TbMRPA. Thereby, the medical treatment with the available chemotherapeutics becomes exceedingly difficult. A promising strategy for research into new drugs and moreover, to overcome drug resistance, are compounds derived from natural sources. This study provides an overview of the recently discovered small molecules with trypanocidal activity against T. b. gambiense and T. b. rhodesiense. In addition, former promising compounds are touched upon.
Truc, Philippe; Lejon, Veerle; Magnus, Eddy; Jamonneau, Vincent; Nangouma, Auguste; Verloo, Didier; Penchenier, Laurent; Büscher, Philippe
OBJECTIVE: To evaluate the performance of serological tests using dried blood on filter-papers (micro-card agglutination test for trypanosomiasis (micro-CATT)) performed under field and laboratory conditions and using whole blood ((CATT/T.b. gambiense) (wb-CATT) and latex agglutination (LATEX/T.b. gambiense) (wb-LATEX)) for the serodiagnosis and surveillance of human African trypanosomiasis in West and Central Africa. METHODS: We evaluated the micro-CATT, wb-CATT and wb-LATEX methods in Côte d'Ivoire and the Central African Republic by screening 940 people. Sensitivity and specificity were calculated for each serological test; only patients with the confirmed presence of trypanosomes in the blood or lymph aspirate were considered true positives. Positive and negative predictive values were also calculated. FINDINGS: Each of the tests showed a lower sensitivity in the Central African Republic than in Côte d'Ivoire. CONCLUSION: The results confirmed the efficiency of the classic wb-CATT to detect sleeping sickness patients. The micro-CATT method can be used for human African trypanosomiasis surveillance if the test is performed on the same day as the blood collection, or if samples are stored at 4 degrees C. Otherwise, micro-CATT can be used when absolute sensitivity is not required. wb-LATEX should only be used for high-specificity screening. PMID:12481210
Characteristics, behaviors and association between Human African Trypanosomiasis and HIV seropositivity among volunteer blood donors in a semi-rural area: A survey from Kikwit, the Democratic Republic of Congo.
Ndilu, Lefils Kasiama; Ekila, Mathilde Bothale; Mayuma, Donald Fundji; Musaka, Alain; Wumba, Roger; Aloni, Michel Ntetani
Blood safety is a major element in the strategy to control the HIV epidemic. The aim of this study was to determine the prevalence and the associated factors of a positive HIV test among blood donors and its association between Human African Trypanosomiasis in Kikwit, the Democratic Republic of Congo. A cross-sectional study was conducted between November 2012 and May 2013. An anonymous questionnaire was designed to extract relevant data. The average mean age of participants was 30 years. The majority were man (67.8%). The overall prevalence of HIV, syphilis, hepatitis B, hepatitis C and human African trypanosomiasis was respectively 3.2%, 1.9%, 1.6%, 1.3% and 1.3%. Alcohol intake, casual unprotected sex, not using condoms during casual sex, sex after alcohol intake and seroprevalence of human African trypanosomiasis were significantly associated with a positive HIV test result ( p<0.05). In this study, sexual risk behaviors were the major risk factors associated with positive HIV tests in blood donors living in Kikwit. It is important to raise awareness about HIV and voluntary blood donation in response to some observations noted in this study such as the low educational level of the blood donors, the low level of knowledge of HIV prevention methods.
Salem, Manar M; Werbovetz, Karl A
Millions of people in the developing world are affected by diseases caused by the kinetoplastid parasites: the leishmaniases, African trypanosomiasis, and Chagas disease. In many cases the drugs employed for treatment are toxic, marginally effective, given by injection, and/or compromised by the development of resistance. Since safe, effective, and affordable chemotherapeutic agents for leishmaniasis and trypanosomiasis are clearly needed, the identification of new antikinetoplastid drug candidates should be an urgent priority. Numerous plant-derived natural products from different structural classes have been investigated as antileishmanial and antitrypanosomal candidates, including various alkaloids, terpenoids, flavonoids, and quinonoids. This review outlines the antikinetoplastid activities of plant-derived natural products reported in the literature and also provides an overview of mechanistic studies that have been conducted with these compounds. Given the activities of these agents and their diverse range of effects on parasite biology, natural products are a potentially rich source of drug candidates and leads against leishmaniasis and trypanosomiasis.
Rashid, Khalid; Wachira, Francis N; Nyariki, James N; Isaac, Alfred O
Human African trypanosomiasis (HAT) is a tropical disease caused by two subspecies of Trypanosoma brucei, the East African variant T. b. rhodesiense and the West African variant T. b. gambiense. Melarsoprol, an organic arsenical, is the only drug used to treat late stage T. b. rhodesiense infection. Unfortunately, this drug induces an extremely severe post treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. A highly reproducible mouse model was adapted to assess the use of Kenyan purple tea anthocyanins and/or coenzyme-Q10 in blocking the occurrence of PTRE. Female Swiss white mice were inoculated intraperitoneally with approximately 10(4) trypanosome isolate T. b. rhodesiense KETRI 2537 and treated sub-curatively 21days post infection with 5mg/kg diminazene aceturate (DA) daily for 3days to induce severe late CNS infection that closely mirrors PTRE in human subjects. Thereafter mice were monitored for relapse of parasitemia after which they were treated with melarsoprol at a dosage of 3.6mg/kg body weight for 4days and sacrificed 24h post the last dosage to obtain brain samples. Brain sections from mice with PTRE that did not receive any antioxidant treatment showed a more marked presence of inflammatory cells, microglial activation and disruption of the brain parenchyma when compared to PTRE mice supplemented with either coenzyme-Q10, purple tea anthocyanins or a combination of the two. The mice group that was treated with coenzyme-Q10 or purple tea anthocyanins had higher levels of GSH and aconitase-1 in the brain compared to untreated groups, implying a boost in brain antioxidant capacity. Overall, coenzyme-Q10 treatment produced more beneficial effects compared to anthocyanin treatment. These findings demonstrate that therapeutic intervention with coenzyme-Q10 and/or purple tea anthocyanins can be used in an experimental mouse model to ameliorate PTRE associated with cerebral HAT.
Annang, F; Pérez-Moreno, G; García-Hernández, R; Cordon-Obras, C; Martín, J; Tormo, J R; Rodríguez, L; de Pedro, N; Gómez-Pérez, V; Valente, M; Reyes, F; Genilloud, O; Vicente, F; Castanys, S; Ruiz-Pérez, L M; Navarro, M; Gamarro, F; González-Pacanowska, D
African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography-mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.
Faria, Joana; Moraes, Carolina B; Song, Rita; Pascoalino, Bruno S; Lee, Nakyung; Siqueira-Neto, Jair L; Cruz, Deu John M; Parkinson, Tanya; Ioset, Jean-Robert; Cordeiro-da-Silva, Anabela; Freitas-Junior, Lucio H
Human African trypanosomiasis (HAT) is a vector-transmitted tropical disease caused by the protozoan parasite Trypanosoma brucei. High-throughput screening (HTS) of small-molecule libraries in whole-cell assays is one of the most frequently used approaches in drug discovery for infectious diseases. To aid in drug discovery efforts for HAT, the SYBR Green assay was developed for T. brucei in a 384-well format. This semi-automated assay is cost- and time-effective, robust, and reproducible. The SYBR Green assay was compared to the resazurin assay by screening a library of 4000 putative kinase inhibitors, revealing a superior performance in terms of assay time, sensitivity, simplicity, and reproducibility, and resulting in a higher hit confirmation rate. Although the resazurin assay allows for comparatively improved detection of slow-killing compounds, it also has higher false-positive rates that are likely to arise from the assay experimental conditions. The compounds with the most potent antitrypanosomal activity were selected in both screens and grouped into 13 structural clusters, with 11 new scaffolds as antitrypanosomal agents. Several of the identified compounds had IC50 <1 µM coupled with high selectivity toward the parasite. The core structures of the scaffolds are shown, providing promising new starting points for drug discovery for HAT.
Bowling, Tana; Mercer, Luke; Don, Robert; Jacobs, Robert; Nare, Bakela
Human African trypanosomiasis (HAT) is caused by the protozoan parasite Trypanosoma brucei, and the disease is fatal if untreated. There is an urgent need to develop new, safe and effective treatments for HAT because current drugs have extremely poor safety profiles and are difficult to administer. Here we report the development and application of a cell-based resazurin reduction assay for high throughput screening and identification of new inhibitors of T. b. brucei as starting points for the development of new treatments for human HAT. Active compounds identified in primary screening of ∼48,000 compounds representing ∼25 chemical classes were titrated to obtain IC50 values. Cytotoxicity against a mammalian cell line was determined to provide indications of parasite versus host cell selectivity. Examples from hit series that showed selectivity and evidence of preliminary SAR were re-synthesized to confirm trypanocidal activity prior to initiating hit-to-lead expansion efforts. Additional assays such as serum shift, time to kill and reversibility of compound effect were developed and applied to provide further criteria for advancing compounds through the hit-to-lead phase of the project. From this initial effort, six distinct chemical series were selected and hit-to-lead chemistry was initiated to synthesize several key analogs for evaluation of trypanocidal activity in the resazurin-reduction assay for parasite viability. From the hit-to-lead efforts, a series was identified that demonstrated efficacy in a mouse model for T. b. brucei infection and was progressed into the lead optimization stage. In summary, the present study demonstrates the successful and effective use of resazurin-reduction based assays as tools for primary and secondary screening of a new compound series to identify leads for the treatment of HAT.
Wenzler, Tanja; Yang, Sihyung; Braissant, Olivier; Boykin, David W; Brun, Reto; Wang, Michael Zhuo
Human African trypanosomiasis (HAT, also called sleeping sickness), a neglected tropical disease endemic to sub-Saharan Africa, is caused by the parasites Trypanosoma brucei gambiense and T. brucei rhodesiense. Current drugs against this disease have significant limitations, including toxicity, increasing resistance, and/or a complicated parenteral treatment regimen. DB829 is a novel aza-diamidine that demonstrated excellent efficacy in mice infected with T. b. rhodesiense or T. b. brucei parasites. The current study examined the pharmacokinetics, in vitro and in vivo activity against T. b. gambiense, and time of drug action of DB829 in comparison to pentamidine. DB829 showed outstanding in vivo efficacy in mice infected with parasites of T. b. gambiense strains, despite having higher in vitro 50% inhibitory concentrations (IC50s) than against T. b. rhodesiense strain STIB900. A single dose of DB829 administered intraperitoneally (5 mg/kg of body weight) cured all mice infected with different T. b. gambiense strains. No cross-resistance was observed between DB829 and pentamidine in T. b. gambiense strains isolated from melarsoprol-refractory patients. Compared to pentamidine, DB829 showed a greater systemic exposure when administered intraperitoneally, partially contributing to its improved efficacy. Isothermal microcalorimetry and in vivo time-to-kill studies revealed that DB829 is a slower-acting trypanocidal compound than pentamidine. A single dose of DB829 (20 mg/kg) administered intraperitoneally clears parasites from mouse blood within 2 to 5 days. In summary, DB829 is a promising preclinical candidate for the treatment of first- and second-stage HAT caused by both Trypanosoma brucei subspecies.
Thuita, John K; Wolf, Kristina K; Murilla, Grace A; Bridges, Arlene S; Boykin, David W; Mutuku, James N; Liu, Qiang; Jones, Susan K; Gem, Charles O; Ching, Shelley; Tidwell, Richard R; Wang, Michael Z; Paine, Mary F; Brun, Reto
Human African trypanosomiasis (HAT, sleeping sickness) ranks among the most neglected tropical diseases based on limited availability of drugs that are safe and efficacious, particularly against the second stage (central nervous system [CNS]) of infection. In response to this largely unmet need for new treatments, the Consortium for Parasitic Drug Development developed novel parenteral diamidines and corresponding oral prodrugs that have shown cure of a murine model of second stage HAT. As a rationale for selection of one of these compounds for further development, the pharmacokinetics and efficacy of intramuscular (IM) active diamidine 2,5-bis(5-amidino-2-pyridyl)furan (DB829; CPD-0802) and oral prodrug2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868) were compared in the vervet monkey model of second stage HAT. Treatment was initiated 28 days post-infection of monkeys with T. b. rhodesiense KETRI 2537. Results showed that IM DB829 at 5 mg/kg/day for 5 consecutive days, 5 mg/kg/day every other day for 5 doses, or 2.5 mg/kg/day for 5 consecutive days cured all monkeys (5/5). Oral DB868 was less successful, with no cures (0/2) at 3 mg/kg/day for 10 days and cure rates of 1/4 at 10 mg/kg/day for 10 days and 20 mg/kg/day for 10 days; in total, only 2/10 monkeys were cured with DB868 dose regimens. The geometric mean plasma Cmax of IM DB829 at 5 mg/kg following the last of 5 doses was 25-fold greater than that after 10 daily oral doses of DB868 at 20 mg/kg. These data suggest that the active diamidine DB829, administered IM, should be considered for further development as a potential new treatment for second stage HAT.
Solano, P; Kone, A; Garcia, A; Sane, B; Michel, V; Michel, J F; Coulibaly, B; Jamonneau, V; Kaba, D; Dupont, S; Fournet, F
Human African trypanosomosis (HAT) remains a major public health problem in Subsaharan Africa. The region around the town of Bonon in middle western Côte d'Ivoire is a highly endemic HAT zone. The purpose of this study was to assess the role of travelling of infected patients in transmission of HAT. The study population included a total of 96 patients in whom HAT had been diagnosed actively or passively between 1999 and 2000. Information on each patient's residence and workplaces, i.e. water site, and farm field, was used to calculate the mean distance traveled and mean number of places visited daily by each patient. Findings indicated that both parameters, i.e., distance traveled and number of places visited, were significantly higher for patients living in Bonon than those living in hamlets or homesteads. Based on analysis of patient movements the endemic zone could be divided into three subdivisions with different modes of disease transmission. This study was performed as a preliminary step for a larger investigation designed to allow specific targeting of HAT hot spots based mainly on a geographic information system.
Waema, Maxwell W; Maina, Naomi W; Ngotho, Maina; Karanja, Simon M; Gachie, Beatrice M; Maranga, Dawn N; Kagira, John M
Human African trypanosomiasis (HAT) patients manifest immunological profiles, whose variations over time can be used to indicate disease progression. However, monitoring of these biomarkers in human patients is beset by several limitations which can be offset by using chronic animal models. A recent improved monkey model of HAT using a Trypanosoma brucei brucei isolate has been developed but the immunological profile has not been elucidated. The objectives of the current study was to determine the IgM, IgG and IL-6 profiles in blood and cerebrospinal fluid (CSF) in vervet monkeys infected with T. b. brucei. Three vervet monkeys were infected intravenously with 10(5)T. b. brucei, monitored for disease development and subsequently treated 28days post infection (dpi) sub-curatively using diminazene aceturate (DA) to induce late stage disease and curatively treated with melarsoprol (Mel B) at 119 dpi, respectively. Matched serum and cerebrospinal fluid (CSF) samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) were quantified by ELISA while IL-6 was assayed using a cytometric bead array (CBA) kit. Results showed that following infection, CSF IgM, IgG, IL-6 and serum IL-6 were significantly (p<0.05) elevated with peak levels coinciding with relapse parasitaemia. The IgG levels increased to reach OD peak levels of 0.442±0.5 at 126 dpi. After curative treatment with MelB, the serum IgM and Ig G levels fell rapidly to attain pre-infection levels within 35 and 49days, respectively. This shows that the profile of these immunoglobulins can be used as an indicator of curative treatment. CSF IL-6 concentrations of infected vervet monkeys showed no significant change (P>0.05) between infection and 35 dpi but levels increased significantly (P<0.05) with the highest level of 55.53pg/ml recorded at112 dpi. IL-6 elevation from 35 dpi may be indicative of parasite neuroinvasion hence can be used as possible candidate marker for late stage disease
Lead Optimization of a Pyrazole Sulfonamide Series of Trypanosoma bruceiN-Myristoyltransferase Inhibitors: Identification and Evaluation of CNS Penetrant Compounds as Potential Treatments for Stage 2 Human African Trypanosomiasis
Trypanosoma bruceiN-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood–brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT. PMID:25412409
Lead optimization of a pyrazole sulfonamide series of Trypanosoma brucei N-myristoyltransferase inhibitors: identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human African trypanosomiasis.
Brand, Stephen; Norcross, Neil R; Thompson, Stephen; Harrison, Justin R; Smith, Victoria C; Robinson, David A; Torrie, Leah S; McElroy, Stuart P; Hallyburton, Irene; Norval, Suzanne; Scullion, Paul; Stojanovski, Laste; Simeons, Frederick R C; van Aalten, Daan; Frearson, Julie A; Brenk, Ruth; Fairlamb, Alan H; Ferguson, Michael A J; Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D
Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood-brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT.
Stanton, M C
Disease control and elimination programmes can benefit greatly from accurate information on the spatial variability of disease risk, particularly when risk is highly spatially heterogeneous. Due to advances in statistical methodology, coupled with the increased availability of geospatial technology, this information is becoming increasingly accessible. In this chapter we describe recent advancements in spatial methods associated with the analysis of disease data measured at the point-level and demonstrate their application to the control and elimination of neglected tropical diseases (NTDs). We further provide information on spatially referenced data sources and software that can be used to create NTD risk maps, concentrating on those that can be freely obtained. Examples relating to three NTDs affecting populations in sub-Saharan Africa are presented throughout the chapter, i.e., human African trypanosomiasis, schistosomiasis and lymphatic filariasis. These three diseases, with differing routes of transmission, control methods and level of spatial heterogeneity, demonstrate the flexibility and applicability of the methods described.
Carod-Artal, Francisco Javier
American (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis.
Oddó, D; Casanova, M; Acuña, G; Ballesteros, J; Morales, B
Two heterosexual men, aged 31 and 40 years, with the acquired immunodeficiency syndrome and presenting with the acute form of Chagas' disease are reported. The first patient, a carrier of hemophilia A, was treated for 20 years with Chilean and Brazilian cryoprecipitates. This patient acquired both diseases through this medium. The second patient, an inhabitant of northern Chile (fourth region), was allegedly bitten by Triatoma infestans and was an intravenous drug addict. The hemophilic patient presented with a neurologic syndrome; a brain biopsy showed a necrotizing encephalitis with an obliterative angiitis and abundant macrophages. The second patient developed intractable congestive heart failure; necropsy showed a dilated myocarditis with rupture of myofibers and an inflammatory infiltrate rich in plasma cells, lymphocytes, and macrophages. Using light and electron microscopy, abundant amastigotes of Trypanosoma cruzi were seen in brain tissue, especially in the cytoplasm of macrophages, as well as in some myocardial fibers. In both cases, determination of anti-T cruzi antibodies (indirect hemagglutination technique) and xenodiagnosis were positive.
WITH DL-ALPHA-DIFLUOROMETHYLORNiTHINE (DFMO) SUBTITLE: Chemotherapy for African Trypanosomiasis by Polyamine Synthesis Inhibition PRINCIPAL...PAGE COUNT Annual Report I FROM 8/15/87 TO 814/88 1988 September 14 22 16. SUPPLEMENTARY NOTATION Subtitle: Chemotherapy for African Trypanosomiasis ...block number) Towards developing a new chemotherapy for African trypanosomiasis , nine strains of Trypanosoma brucei rhodesiense were acquired and used
Pharmacokinetics and pharmacodynamics utilizing unbound target tissue exposure as part of a disposition-based rationale for lead optimization of benzoxaboroles in the treatment of Stage 2 Human African Trypanosomiasis.
Wring, Stephen; Gaukel, Eric; Nare, Bakela; Jacobs, Robert; Beaudet, Beth; Bowling, Tana; Mercer, Luke; Bacchi, Cyrus; Yarlett, Nigel; Randolph, Ryan; Parham, Robin; Rewerts, Cindy; Platner, Jacob; Don, Robert
SUMMARY This review presents a progression strategy for the discovery of new anti-parasitic drugs that uses in vitro susceptibility, time-kill and reversibility measures to define the therapeutically relevant exposure required in target tissues of animal infection models. The strategy is exemplified by the discovery of SCYX-7158 as a potential oral treatment for stage 2 (CNS) Human African Trypanosomiasis (HAT). A critique of current treatments for stage 2 HAT is included to provide context for the challenges of achieving target tissue disposition and the need for establishing pharmacokinetic-pharmacodynamic (PK-PD) measures early in the discovery paradigm. The strategy comprises 3 stages. Initially, compounds demonstrating promising in vitro activity and selectivity for the target organism over mammalian cells are advanced to in vitro metabolic stability, barrier permeability and tissue binding assays to establish that they will likely achieve and maintain therapeutic concentrations during in-life efficacy studies. Secondly, in vitro time-kill and reversibility kinetics are employed to correlate exposure (based on unbound concentrations) with in vitro activity, and to identify pharmacodynamic measures that would best predict efficacy. Lastly, this information is used to design dosing regimens for pivotal pharmacokinetic-pharmacodyamic studies in animal infection models.
Stage determination and therapeutic decision in human African trypanosomiasis: value of polymerase chain reaction and immunoglobulin M quantification on the cerebrospinal fluid of sleeping sickness patients in Côte d'Ivoire.
Jamonneau, V; Solano, P; Garcia, A; Lejon, V; Djé, N; Miezan, T W; N'Guessan, P; Cuny, G; Büscher, P
In human African trypanosomiasis (HAT), two disease stages are defined: the first, or haemo-lymphatic stage, and the second, or meningo-encephalitic stage. Stage determination forms the basis of therapeutic decision and is of prime importance, as the drug used to cure second-stage patients has considerable side-effects. However, the tests currently used for stage determination have low sensitivity or specificity. Two new tests for stage determination in the cerebrospinal fluid (CSF) were evaluated on 73 patients diagnosed with HAT in Côte d'Ivoire. The polymerase chain reaction (PCR) detecting trypanosome DNA (PCR/CSF) is an indirect test for trypanosome detection whereas the latex agglutination test detecting immunoglobulin M (LATEX/IgM) is an indicator for neuro-inflammation. Both tests were compared with classically used tests, double centrifugation and white blood cell count of the CSF. PCR/CSF appeared to be the most sensitive test (96%), and may be of use to improve stage determination. However, its value for therapeutic decision appears limited, as patients whose CSF was positive with PCR were successfully treated with pentamidine. This result confirms those of previous works that showed that some patients with trypanosomes in the CSF could be treated successfully with pentamidine. LATEX/IgM, which depending on the cut-off, showed lower sensitivity of 76% and 88%, but higher specificity of 83% and 71% for LATEX/IgM 16 and LATEX/IgM 8 respectively, appears more appropriate for therapeutic decision making.
Macleod, Ewan T.; Anderson, Neil E.; Schaten, Kathrin; Kuleszo, Joanna; Simuunza, Martin; Welburn, Susan C.; Atkinson, Peter M.
Background This paper presents a new agent-based model (ABM) for investigating T. b. rhodesiense human African trypanosomiasis (rHAT) disease dynamics, produced to aid a greater understanding of disease transmission, and essential for development of appropriate mitigation strategies. Methods The ABM was developed to model rHAT incidence at a fine spatial scale along a 75 km transect in the Luangwa Valley, Zambia. The method offers a complementary approach to traditional compartmentalised modelling techniques, permitting incorporation of fine scale demographic data such as ethnicity, age and gender into the simulation. Results Through identification of possible spatial, demographic and behavioural characteristics which may have differing implications for rHAT risk in the region, the ABM produced output that could not be readily generated by other techniques. On average there were 1.99 (S.E. 0.245) human infections and 1.83 (S.E. 0.183) cattle infections per 6 month period. The model output identified that the approximate incidence rate (per 1000 person-years) was lower amongst cattle owning households (0.079, S.E. 0.017), than those without cattle (0.134, S.E. 0.017). Immigrant tribes (e.g. Bemba I.R. = 0.353, S.E.0.155) and school-age children (e.g. 5–10 year old I.R. = 0.239, S.E. 0.041) were the most at-risk for acquiring infection. These findings have the potential to aid the targeting of future mitigation strategies. Conclusion ABMs provide an alternative way of thinking about HAT and NTDs more generally, offering a solution to the investigation of local-scale questions, and which generate results that can be easily disseminated to those affected. The ABM can be used as a tool for scenario testing at an appropriate spatial scale to allow the design of logistically feasible mitigation strategies suggested by model output. This is of particular importance where resources are limited and management strategies are often pushed to the local scale. PMID:28027323
efficacy of different tratment regimens and for calculating the optimum duration of treatment. A comparison of microscopy and culture in the detection...congolense: Thrombocyte Survival in Infected Steers. Exp. Parasit. 54, 129-133. 3. Roberts, L.W., Boyce, W.L. and Lyerly, W.H.: Cordylobia...Chulay, J.D. and Bryceson, A.D.M.: A Comparison of Microscopy and Culture in the Detection of Leishmania donovani from Splenic Aspirates. Am. J. Trop. Med
King, Susan E.
Case studies are presented of three African-American women who earned doctoral degrees in physical education and sport disciplines between 1971 and 1990. Personal interviews were conducted with the informants on issues related to the campus environment as well as financial and academic factors. The case studies are analyzed in terms of the women's…
Hardwick, Robert J; Ménard, Anne; Sironi, Manuela; Milet, Jacqueline; Garcia, André; Sese, Claude; Yang, Fengtang; Fu, Beiyuan; Courtin, David; Hollox, Edward J
Haptoglobin, coded by the HP gene, is a plasma protein that acts as a scavenger for free heme, and haptoglobin-related protein (coded by the HPR gene) forms part of the trypanolytic factor TLF-1, together with apolipoprotein L1 (ApoL1). We analyse the polymorphic small intragenic duplication of the HP gene, with alleles Hp1 and Hp2, in 52 populations, and find no evidence for natural selection either from extended haplotype analysis or from correlation with pathogen richness matrices. Using fiber-FISH, the paralog ratio test, and array-CGH data, we also confirm that the HPR gene is copy number variable, with duplication of the whole HPR gene at polymorphic frequencies in west and central Africa, up to an allele frequency of 15 %. The geographical distribution of the HPR duplication allele overlaps the region where the pathogen causing chronic human African trypanosomiasis, Trypanosoma brucei gambiense, is endemic. The HPR duplication has occurred on one SNP haplotype, but there is no strong evidence of extended homozygosity, a characteristic of recent natural selection. The HPR duplication shows a slight, non-significant undertransmission to human African trypanosomiasis-affected children of unaffected parents in the Democratic Republic of Congo. However, taken together with alleles of APOL1, there is an overall significant undertransmission of putative protective alleles to human African trypanosomiasis-affected children.
Simo, Gustave; Rayaisse, Jean Baptiste
African trypanosomiases are infectious diseases caused by trypanosomes. African animal trypanosomiasis (AAT) remains an important threat for livestock production in some affected areas whereas human African trypanosomiasis (HAT) is targeted for elimination in 2020. In West and Central Africa, it has been shown that the parasites causing these diseases can coexist in the same tsetse fly or the same animal. In such complex settings, the control of these diseases must be put in the general context of trypanosomiasis control or "one health" concept where the coordination of control operations will be beneficial for both diseases. In this context, implementing control activities on AAT will help to sustain HAT control. It will also have a positive impact on animal health and economic development of the regions. The training of inhabitants on how to implement and sustain vector control tools will enable a long-term sustainability of control operations that will lead to the elimination of HAT and AAT.
Stijlemans, Benoît; Vankrunkelsven, Ann; Caljon, Guy; Bockstal, Viki; Guilliams, Martin; Bosschaerts, Tom; Beschin, Alain; Raes, Geert; Magez, Stefan; De Baetselier, Patrick
Bovine African trypanosomiasis causes severe economical problems on the African continent and one of the most prominent immunopathological parameters associated with this parasitic infection is anemia. In this report we review the current knowledge of the mechanisms underlying trypanosomiasis-associated anemia. In first instance, the central role of macrophages and particularly their activation state in determining the outcome of the disease (i.e. trypanosusceptibility versus trypanotolerance) will be discussed. In essence, while persistence of classically activated macrophages (M1) contributes to anemia development, switching towards alternatively activated macrophages (M2) alleviates pathology including anemia. Secondly, while parasite-derived glycolipids such as the glycosylphosphatidylinositol (GPI) induce M1, host-derived IL-10 blocks M1-mediated inflammation, promotes M2 development and prevents anemia development. In this context, strategies aimed at inducing the M1 to M2 switch, such as GPI-based treatment, adenoviral delivery of IL-10 and induction of IL-10 producing regulatory T cells will be discussed. Finally, the crucial role of iron-homeostasis in trypanosomiasis-associated anemia development will be documented to stress the analogy with anemia of chronic disease (ACD), hereby providing new insight that might contribute to the treatment of ACD.
Vankrunkelsven, Ann; De Ceulaer, Kris; Hsu, Daniel; Liu, Fu-Tong; De Baetselier, Patrick; Stijlemans, Benoît
A typical pathological feature associated with experimental African trypanosomiasis (Trypanosoma brucei infection in mice) is anemia of chronic disease (ACD), which is due to a sustained type 1 cytokine-mediated inflammation and hyperactivation of M1 macrophages. Galectin-3 (Gal-3) was amply documented to contribute to the onset and persistence of type 1 inflammatory responses and we herein document that this protein is strongly upregulated during T. brucei infection. We evaluated the involvement of Gal-3 in trypanosomiasis-associated anemia using galectin-3 deficient (Gal3(-/-)) mice. T. brucei infected Gal3(-/-) mice manifested significant lower levels of anemia during infection and survived twice as long as wild type mice. Moreover, such mice showed increased levels of serum IL-10 and reduced liver pathology (as evidenced by lower AST/ALT levels). In addition, there was also an increase in gene expression of iron export genes and a reduced expression of genes, which are associated with accumulation of cellular iron. Our data indicate that Gal-3 is involved in the development of inflammation-associated anemia during African trypanosomiasis, possibly due to a disturbed iron metabolism that in turn may also lead to liver malfunction.
history , dietary patterns, and nutrient levels will be compared between cases and controls to determine the fatty acid risk factors for prostate cancer...564 848 Table 17: History of Previous DRE among Study Participants Ethno-Cultural Group Previous DRE African- American African...Know 32(50.0) 2(100.0) 34 51.5 Total 64 2 66 Table 20: History of Urinary Symptoms among Study Participants Ethno
Navarrete-Sandoval, Rafael Hernán; Servín-Rojas, Maximiliano
Patient: Male, 44 Final Diagnosis: Acute phase Chagas disease Symptoms: Fever • headache • periorbital oedema Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: Chagas disease is a chronic parasitosis transmitted by the inoculation of infected triatomine feces into wounds or conjunctival sac, transfusion, congenitally, organ transplantation, and ingestion of contaminated food. The disease is classified into an acute and chronic phase; the latter is a life-long infection that can be asymptomatic or progress to cardiac or digestive complications. Case Report: We report a case of acute-phase Chagas disease, transmitted by the splash of gut content from an infected triatomine into the conjunctival mucosa. Conclusions: The diagnosis of Chagas disease is made by the direct visualization of the parasite in blood smears during the acute phase of the disease; during the chronic phase of the disease the diagnosis is made by the detection of IgG antibodies. Parasitological cure can be achieved in up to 80% of the cases in acute phase of the disease, in contrast with less than 30% during the chronic phase. PMID:28031550
Senegal, Pamela Gibson
This research is a qualitative case study exploring the experiences of African American male mentoring community college students. Such programs have proliferated throughout higher education, over the past 20 years, in an effort to improve the retention, performance and goal attainment of African American males. The theoretical framework shaping…
The paper has a twofold structure and focus. The first part is an examination of the funding challenges facing African universities resulting mainly from public finance difficulties, and the second part is a case study of how some Kenyan and South African public universities have attempted to mitigate resource dependence difficulties through…
James, LaNora Marcell
The purpose of the qualitative collective case study is to identify the weaknesses in the methods used to recruit highly qualified African American preservice teachers in the Washington, DC metropolitan area. The data collection process consisted of one-on-one, open-ended interview questions with 10 highly qualified African American public school…
The purpose of this study was to describe and explain the 5th grade mathematics teaching practice of an African American female teacher in a predominantly African American classroom that consistently meets and/or exceeds Michigan's mathematics proficiency standards. Using multiple emancipatory lenses, and a single case study method that employed…
Treiman, Rebecca; Bowman, Margo
This study examined the effect of dialect variation on children's spelling by using devoicing of final /d/ in African American Vernacular English (AAVE) as a test case. In line with the linguistic interference hypothesis, African American 6-year-olds were significantly poorer at spelling the final "d" of words such as "salad"…
The purpose of this study is to investigate the reading competence of teachers who are enrolled in a distance education programme in a South African university. Many South African teachers upgrade their teaching diplomas by enrolling for a part-time, distance degree at a university. However, many are not prepared for academic study and its focus…
Van den Bossche, Peter; de La Rocque, Stéphane; Hendrickx, Guy; Bouyer, Jérémy
The distribution, prevalence and impact of vector-borne diseases are often affected by anthropogenic environmental changes that alter the interactions between the host, the parasite and the vector. In the case of tsetse-transmitted livestock trypanosomiasis these changes are a result of the encroachment of people and their livestock into tsetse-infected wild areas. This has created a sequence of new epidemiological settings that is changing the relative importance of the domestic or sylvatic trypanosome transmission cycles and is causing concomitant changes in the impact of the disease on livestock. These changes in the dynamics of the epidemiology have an important impact on the factors that need to be considered when developing area-specific strategies for the future management of tsetse-transmitted livestock trypanosomiasis.
Ncube, Caroline B.
This report draws primarily on the results of the recently concluded African Copyright and Access to Knowledge (ACA2K) Project, which investigated copyright and access to learning materials in face-to-face, distance education (DE), and dual-mode tertiary educational institutions in Egypt, Ghana, Kenya, Morocco, Mozambique, Senegal, South Africa,…
ml 0.9% saline and centrifuged at 250 x G for 15 min. (This and all subsequent centrifugations were done at room temperature .) The plate- let-rich...Co., St. Louis, MO, USA) and allowed to sediment 45 min at room temperature . The leu- kocyte-rich plasma was removed, 6 ml was layered over 3 ml of a...to a small slice of apple which was changed daily. All blood feeding was done in the early morning when ambient temperatures were lowest and light
Özkan, Gülsüm; Ulusoy, Şükrü
Chronic kidney disease continues to represent a significant health problem in all societies. One of the main factors accelerating renal progression is nephrotoxins. The African mango is a plant added to many foods and commonly consumed in West Africa. No toxic effect has to date been shown. Our aim was to discuss the 42-year-old patient who became dialysis-dependent through developing rapid renal progression following 2.5-month African mango use. To the best of our knowledge, our patient is the first case of chronic renal insufficiency developing in association with African mango consumption. PMID:26131261
Özkan, Gülsüm; Ulusoy, Şükrü
Chronic kidney disease continues to represent a significant health problem in all societies. One of the main factors accelerating renal progression is nephrotoxins. The African mango is a plant added to many foods and commonly consumed in West Africa. No toxic effect has to date been shown. Our aim was to discuss the 42-year-old patient who became dialysis-dependent through developing rapid renal progression following 2.5-month African mango use. To the best of our knowledge, our patient is the first case of chronic renal insufficiency developing in association with African mango consumption.
... by testing with at least two different serologic tests. Related Links For more information about laboratory diagnosis of Chagas disease, see the DPDx Web site: Chagas disease (American Trypanosomiasis) Diagnostic Procedures: Blood ...
de Villiers, Alethea
In this paper I reflect on transformation in South African education policy, post-1994. The new curriculum for schools was underpinned by the democratic values of the constitution and was a time of renewal for music education. However, over time as the original curriculum documents were revised, the focus of promoting indigenous traditions was…
Walker, Melanie; Loots, Sonja
The paper considers citizenship formation at universities, drawing on the example of a student leadership project at the University of the Free State, a formerly White South African university, in a higher education context and society where racialised difference continues to influence peer relationships. The paper proposes a multi-dimensional…
Ding, Yuan Chun; Steele, Linda; Chu, Li-Hao; Kelley, Karen; Davis, Helen; John, Esther M; Tomlinson, Gail E; Neuhausen, Susan L
Breast cancer incidence is lower in African Americans than in Caucasian Americans. However, African-American women have higher breast cancer mortality rates and tend to be diagnosed with earlier-onset disease. Identifying factors correlated to the racial/ethnic variation in the epidemiology of breast cancer may provide better understanding of the more aggressive disease at diagnosis. Truncating germline mutations in PALB2 have been identified in approximately 1% of early-onset and/or familial breast cancer cases. To date, PALB2 mutation testing has not been performed in African-American breast cancer cases. We screened for germline mutations in PALB2 in 139 African-American breast cases by denaturing high-performance liquid chromatography and direct sequencing. Twelve variants were identified in these cases and none caused truncation of the protein. Three missense variants, including two rare variants (P8L and T300I) and one common variant (P210L), were predicted to be pathogenic, and were located in a coiled-coil domain of PALB2 required for RAD51- and BRCA1-binding. We investigated and found no significant association between the P210L variant and breast cancer risk in a small case-control study of African-American women. This study adds to the literature that PALB2 mutations, although rare, appear to play a role in breast cancer in all populations investigated to date.
indefinite; its animal victims die of exhaustion. However, the classic iodine-iodide treatment for human sporotrichosis was found to be effective. This...particular sporotrichosis is of interest in human clinical study, since it can be transmitted from the animal to a healthy human. In fact, this first African case of human sporotrichosis was a case of mule-to-man infection.
Rule, P.; Davey, B.; Balfour, R. J.
The Project Postgraduate Educational Research (PPER) data indicate that case study is the most popular methodology among South African education masters and doctorate students in the period 1995-2004. This article reflects on the reasons for the preference for case study by considering epistemological and contextual factors. It unpacks the links…
At present there is a steady rise in African sleeping sickness (trypanosomiasis) transmitted by the Tsetse fly, and which if left untreated, is fatal. Thanks to more than so years of neglect by research, our therapeutic repertoire is limited to medications with a high level of toxicity. Both WHO and international aid organizations are pushing hard for the development of new, more efficient drugs that can be readily applied in the field.
Graber, Mark; Bolt, Susan
In this case study the delivery of business courses as a result of the partnership between the African Virtual University (AVU) and Curtin University in Western Australia is described. From 2004 to 2008, degree and diploma business courses were delivered using WebCT in the four AVU partner locations: Addis Ababa University (Ethiopia), Kigali…
Makoe, Pinky; McKinney, Carolyn
The data discussed in this paper is drawn from research conducted in a multilingual urban primary school in Johannesburg, South Africa, where the official language of instruction is English and the majority of learners are African language speakers, frequently with very limited English proficiency. The paper presents a case study of one child who…
Bothun, Gregory D.
Purpose: The purpose of this paper is to provide a case study report of the development of data networks and initial connectivity in the Sub-Saharan African (SSA) region and how that development evolved into the formation of research and education (R&E) networks that enable new collaborations and curriculum potential.…
Dovey, Ken; Onyx, Jenny
A case study of a South African workplace illustrated how workplace learning and experience of team culture influenced changes in workers' family life and community participation. Results showed how social capital is generated from within for the benefit of civil society. (Contains 35 references.) (SK)
McDaniel, Brenda J.
The purpose of this collective embedded qualitative case study was to examine the perspectives of three middle-aged independent-living African Americans who had participated in the process of advance care planning (ACP) and completed at least two advance directives (ADs), a Durable Power of Attorney for Health Care (DPAHC) and a Living Will (LW).…
Rutten-Jacobs, Loes; Curtis, Charles; Patel, Hamel; Breen, Gerome; Newhouse, Stephen; Lewis, Cathryn M.; Markus, Hugh S.
Objective: Despite epidemiologic data showing an increased stroke incidence in African ancestry populations, genetic studies in this group have so far been limited, and there has been little characterization of the genetic contribution to stroke liability in this population, particularly for stroke subtypes. Methods: We evaluated the evidence that genetic factors contribute to stroke and stroke subtypes in a population of 917 African and African Caribbean stroke cases and 868 matched controls from London, United Kingdom. We (1) estimated the heritability of stroke in this population using genomic-relatedness matrix-restricted maximum likelihood approaches, (2) assessed loci associated with stroke in Europeans in our population, and (3) evaluated the influence of genetic factors underlying cardiovascular risk factors on stroke using polygenic risk scoring. Results: Our results indicate a substantial genetic contribution to stroke risk in African ancestry populations (h2 = 0.35 [SE = 0.19], p = 0.043). Polygenic risk scores indicate that cardiovascular risk scores contribute to the genetic liability (odds ratio [OR] 1.09 [95% confidence interval (CI) 1.01–1.17], p = 0.029) and point to a strong influence of type 2 diabetes in large vessel stroke (OR 1.62 [95% CI 1.19–2.22], p = 0.0024). Single nucleotide polymorphisms associated with ischemic stroke in Europeans shared direction of effect in SLESS (p = 0.031), suggesting that disease mechanisms are shared across ancestries. Conclusions: Stroke in African ancestry populations is highly heritable and influenced by genetic determinants underlying cardiovascular risk factors. In addition, stroke loci identified in Europeans share direction of effect in African populations. Future genome-wide association studies must focus on incorporating African ancestry individuals. PMID:28349126
Schofield, Chris J; Kabayo, John P
Vectors of trypanosomiasis – tsetse (Glossinidae) in Africa, kissing-bugs (Triatominae) in Latin America – are very different insects but share demographic characteristics that render them highly vulnerable to available control methods. For both, the main operational problems relate to re-invasion of treated areas, and the solution seems to be in very large-scale interventions covering biologically-relevant areas rather than adhering to administrative boundaries. In this review we present the underlying rationale, operational background and progress of the various trypanosomiasis vector control initiatives active in both continents. PMID:18673535
Jewkes, Rachel; Christofides, Nicola; Vetten, Lisa; Jina, Ruxana; Sigsworth, Romi; Loots, Lizle
Background Health services for victims of rape are recognised as a particularly neglected area of the health sector internationally. Efforts to strengthen these services need to be guided by clinical research. Expert medical evidence is widely used in rape cases, but its contribution to the progress of legal cases is unclear. Only three studies have found an association between documented bodily injuries and convictions in rape cases. This article aims to describe the processing of rape cases by South African police and courts, and the association between documented injuries and DNA and case progression through the criminal justice system. Methods and Findings We analysed a provincially representative sample of 2,068 attempted and completed rape cases reported to 70 randomly selected Gauteng province police stations in 2003. Data sheets were completed from the police dockets and available medical examination forms were copied. 1,547 cases of rape had medical examinations and available forms and were analysed, which was at least 85% of the proportion of the sample having a medical examination. We present logistic regression models of the association between whether a trial started and whether the accused was found guilty and the medico-legal findings for adult and child rapes. Half the suspects were arrested (n = 771), 14% (209) of cases went to trial, and in 3% (31) of adults and 7% (44) of children there was a conviction. A report on DNA was available in 1.4% (22) of cases, but the presence or absence of injuries were documented in all cases. Documented injuries were not associated with arrest, but they were associated with children's cases (but not adult's) going to trial (adjusted odds ratio [AOR] for having genital and nongenital injuries 5.83, 95% confidence interval [CI] 1.87–18.13, p = 0.003). In adult cases a conviction was more likely if there were documented injuries, whether nongenital injuries alone AOR 6.25 (95% CI 1.14–34.3, p = 0
Willis, Belinda F.
Literature that addresses how the arts enhance student learning through creative expression is minimal. This is especially true for African-American elementary students from high-poverty backgrounds. The purpose of this study was to employ a case study design to explore how African-American elementary students in high-poverty schools experience…
du Plessis, Andre; Webb, Paul
This case study, involving 30 participating teachers from six previously disadvantaged South African schools, provides data on teacher perceptions of the challenges related to implementing Information and Communication Technology (ICT). The schools had minimal resources as a residual result of the South African apartheid policy prior to 1994 and…
While all educational leaders face challenges in achieving success, African American female principals often face a unique set of challenges associated with the complexity of their gender, race, and, as examined in this study, age. This case study investigates the experiences of two highly visible, early career African American female principals…
Grant, Catherine; Anderson, Neil; Machila, Noreen
Background This paper explores the framings of trypanosomiasis, a widespread and potentially fatal zoonotic disease transmitted by tsetse flies (Glossina species) affecting both humans and livestock. This is a country case study focusing on the political economy of knowledge in Zambia. It is a pertinent time to examine this issue as human population growth and other factors have led to migration into tsetse-inhabited areas with little historical influence from livestock. Disease transmission in new human-wildlife interfaces such as these is a greater risk, and opinions on the best way to manage this are deeply divided. Methods A qualitative case study method was used to examine the narratives on trypanosomiasis in the Zambian policy context through a series of key informant interviews. Interviewees included key actors from international organisations, research organisations and local activists from a variety of perspectives acknowledging the need to explore the relationships between the human, animal and environmental sectors. Principal Findings Diverse framings are held by key actors looking from, variously, the perspectives of wildlife and environmental protection, agricultural development, poverty alleviation, and veterinary and public health. From these viewpoints, four narratives about trypanosomiasis policy were identified, focused around four different beliefs: that trypanosomiasis is protecting the environment, is causing poverty, is not a major problem, and finally, that it is a Zambian rather than international issue to contend with. Within these narratives there are also conflicting views on the best control methods to use and different reasoning behind the pathways of response. These are based on apparently incompatible priorities of people, land, animals, the economy and the environment. The extent to which a One Health approach has been embraced and the potential usefulness of this as a way of reconciling the aims of these framings and narratives is
Carabarin-Lima, Alejandro; González-Vázquez, María Cristina; Rodríguez-Morales, Olivia; Baylón-Pacheco, Lidia; Rosales-Encina, José Luis; Reyes-López, Pedro Antonio; Arce-Fonseca, Minerva
Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, a flagellated organism that is transmitted mainly to humans through the infected feces of triatomine kissing bugs (vector transmission in endemic areas) or by transfusion of infected blood, donations of infected organ, or transmission from an infected mother to her child at birth. Chagas disease was first described in 1909 by the Brazilian physician Carlos Chagas, and due to the parasite's distribution throughout North, Central and South America, the disease is commonly known as American trypanosomiasis. However, this disease is now present in non-endemic countries such as Canada, the United States of America, and several countries in Europe (principally Spain). Moreover, Chagas disease was recently designated by the World Health Organization as one of the main neglected tropical diseases. The aim of this review is to summarize the research efforts recently described in studies conducted in Mexico on Chagas disease. In this country, there are no existing vector control programs. In addition, there is no consensus on the diagnostic methods for acute and chronic Chagas disease in maternity wards and blood banks, and trypanocidal therapy is not administered to chronic patients. The actual prevalence of the disease is unknown because no official reporting of cases is performed. Therefore, the number of people infected by different routes of transmission (vector, congenital, blood transfusion, organ transplantation, or oral) is unknown. We believe that by promoting education about Chagas disease in schools starting at the basic elementary level and including reinforcement at higher education levels will ensure that the Mexican population would be aware of this health problem and that the control measures adopted will have more acceptance and success. We hope that this review sensitizes the relevant authorities and that the appropriate measures to reduce the risk of infection by T. cruzi
development of several African and South American countries. African trypanosomiasis is ranked among the top six tropical diseases selected for scientific...This enzyme is therefore of interest as a possible target for drug chemotherapy . At present only suramin and organic arsenicals remain as the mainstay...of chemotherapy , despite their many dangerous disadvantages. With the use of a fast protein liquid chromatography (FPLC) system and a Mono Q anion
... swine fever and bovine spongiform encephalopathy. 96.2 Section 96.2 Animals and Animal Products ANIMAL... Prohibition of casings due to African swine fever and bovine spongiform encephalopathy. (b) Casings from... spongiform encephalopathy. (a) Swine casings. The importation of swine casings that originated in or...
Leppard, William; Loungani, Rahul; Saylors, Bradley; Delaney, Kevin
We present a case study of a patient with a rare and disfiguring dermatologic condition known as cornu cutaneum, or giant cutaneous horn (GCH). While this condition has been well described in people of European and Asian ancestry, its presence in African populations is perceived to be rare and has not been reported in the literature until recently. We present the case of cornu cutaneum in a woman of African descent, contributing to the recent evidence that this condition may not be as rare in African populations as believed. Etiologic factors, epidemiology and management are also reviewed.
Meel, B L
Witchcraft and witch-hunt have been practiced widely almost all over the world. It is known as magic in Europe, maleficium (wrong-doing) in Latin America, and superpower in Asia. In Africa those accused of being witches often face execution. A range of accusations are leveled against witches such as causing impotence, turning milk sour, causing disease and death.Three cases are presented here to highlight the issues related to witch craft in Transkei area. The information was given by the next of kin at the time of autopsy. All were elderly women over 50 years of age. The first was related to tuberculosis of the brother of the perpetrator the second, death of the culprit's relative and third the death of culprits brother in Johannesburg. The first and third victims were brutally chopped by axe and in the second it was a firearm injury. The case history, the type of wounds, and medico-legal aspects of death are discussed in these reports. There law related to witchcraft and their implementations to prevent such deaths are discussed.
Katte, Jean-Claude; Djoumessi, Romance; Njindam, Gisele; Fetse, Gerard Tama; Dehayem, Mesmin; Kengne, Andre-Pascal
Type 1 diabetes mellitus is very rare in infants and toddlers and is usually associated with high mortality when complicated with diabetic ketoacidosis (DKA). Toddlers in DKA are often missed in our typical African setting where there is low index of suspicion. Usually, the classical symptoms are not usually at the forefront and many infants and toddlers who develop DKA are mistreated for infections. The case of a 13-months old toddler with new-onset type 1 diabetes mellitus, complicated with DKA at diagnosis is reported in view of its rarity and elevated mortality even when diagnosed in our African setting. She was subsequently treated with intravenous insulin and was passed over to subcutaneous insulin after the eradication of ketones in urine. She continues follow-up at the out-patient children diabetes clinic at the Bafoussam Regional Hospital. PMID:26966489
Langer, Sandra; Ternes, Kerstin; Widmer, Dimitri; Mutschmann, Frank
To the authors knowledge this is the first case of intersexuality in an African dwarf crocodile (Osteolaemus tetraspis). An adult African dwarf crocodile with a male-typical phenotype lived at Zoo Duisburg in Germany for 10 years. It died in October 2012 despite intensive treatment as a result of terminal septicemia. After a detailed pathological examination the gonads were histologically confirmed as ovotestes. Half of the 22 extant species of crocodilians have been examined for occurrence of temperature dependent sex determination (TSD). In TSD reptiles, masculinizing temperatures yield 100% or a majority of males, whereas feminizing temperatures yield 100% or a majority of females. In the transition range of temperature (TRT), a mix of males, females and sometimes intersexes are obtained. However, the molecular mechanisms behind TSD and an explanation for the occurrence of intersexuality remain elusive.
Juma, Magdallen N.
This booklet describes the African Virtual University (AVU), an interactive instructional telecommunications network established to provide distance education to the countries of sub-Saharan Africa. The AVU was piloted in 1997-1998, and in the 1998-1999 academic year, 27 institutions were slated to offer AVU courses. Supported by the World Bank,…
... swine fever and bovine spongiform encephalopathy. 96.2 Section 96.2 Animals and Animal Products ANIMAL... ENTRY INTO THE UNITED STATES § 96.2 Prohibition of casings due to African swine fever and bovine spongiform encephalopathy. (a) Swine casings. The importation of swine casings that originated in or...
... swine fever and bovine spongiform encephalopathy. 96.2 Section 96.2 Animals and Animal Products ANIMAL... ENTRY INTO THE UNITED STATES § 96.2 Prohibition of casings due to African swine fever and bovine spongiform encephalopathy. (a) Swine casings. The importation of swine casings that originated in or...
... swine fever and bovine spongiform encephalopathy. 96.2 Section 96.2 Animals and Animal Products ANIMAL... ENTRY INTO THE UNITED STATES § 96.2 Prohibition of casings due to African swine fever and bovine spongiform encephalopathy. (a) Swine casings. The importation of swine casings that originated in or...
Zumla, A; Huggett, J; Dheda, K; Green, C; Kapata, N; Mwaba, P
We describe the initiation and establishment of The University of Zambia - University College London Medical School (UNZA-UCLMS) Research and Training Project, an entirely African scientist-led, south-north partnership. In its 16 year existence, the project, by successfully obtaining competitive grant funding, has transformed itself into one of Africa's most productive African-led R&D programmes with training and visible research outputs. The project serves as a role model and now networks R&D and training activities with six southern African (10 institutions) and six European countries. This project case study illustrates that deep commitment is essential for success and that the factors which facilitate success in R&D in Africa need to be evaluated. The long-term prospects for sustaining the UNZA-UCLMS Project appear bright and are dependent on several factors: the ability to retain trained African scientists; obtaining continued competitive or donor grant funding support; and serious investment by the African governments involved. The recent 255 million Euros EDCTP investment in sub-Saharan Africa through south-north partnerships is expected to enhance existing African-led R&D programmes. African governments and scientists must rise to the challenge.
Patel, Gautam; Karver, Caitlin E.; Behera, Ranjan; Guyett, Paul; Sullenberger, Catherine; Edwards, Peter; Roncal, Norma E.; Mensa-Wilmot, Kojo; Pollastri, Michael P.
Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Since drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogs of 1, which provided an excellent starting point for optimization of the chemotype. We report our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU621, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new tool for studying regulation of the trypanosome cell cycle. PMID:23597080
Patel, Gautam; Karver, Caitlin E; Behera, Ranjan; Guyett, Paul J; Sullenberger, Catherine; Edwards, Peter; Roncal, Norma E; Mensa-Wilmot, Kojo; Pollastri, Michael P
Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei . Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.
Hart, Juliet E.; Cramer, Elizabeth D.; Harry, Beth; Klingner, Janette K.; Sturges, Keith M.
This article discusses the construction of the "emotional disturbance" (ED) category in the cases of four African American elementary students. These cases represent a sub-set of data from a three-year ethnographic study of the special education process in a large, culturally/linguistically diverse school district. Based on interviews,…
Haywood, Jerry L.
The goal of this study was to examine the experience of African American males who did not achieve academic success in their first year of college at a predominately White institution (PWI) in Southwestern Georgia. This study used a qualitative case study design to investigate the experience held by this target group. The qualitative case study…
Lapão, Luís Velez; Silva, Andreia; Pereira, Natália; Vasconcelos, Paula; Conceição, Cláudia
Introduction Ebola epidemics have shown to have significant impacts on many aspects of healthcare systems. African countries have been facing many difficulties while addressing Ebola epidemics, moreover due to both lack of resources and fragmented involvement of national and international entities. The participation of multiple organizations has created serious problems of coordination of aid and the operation of that aid on the ground. This paper aims at addressing the impact of Ebola epidemics on African health systems, with a special focus on the definition of impact mitigation guidelines and the role of resilience. The example of Portuguese speaking countries is presented. Methods A combination of literature review and case study methods are used. A literature review on Ebola outbreak impact on health systems will provide information to define a set of guidelines for healthcare services response to Ebola. The role of cooperation in providing additional resilience is described. Finally a case study focusing on the Portuguese collaboration and intervention in African Portuguese Speaking Countries (PALOP) is presented, as an example how the international community can provide additional resilience. Results The existing knowledge is very helpful to guide both the preparation and the coordination of Ebola preparedness interventions. Additional resilience can be provided by international cooperation. Conclusion In addition to international concrete support in times of crisis, to have a regional strategy of creating (multi-national) teams to rapidly implement an intervention while establishing better regional capacity to have sufficient resources to support the “resilience” required of the health system. PMID:26740843
Woodring, Jennifer L.; Patel, Gautam; Erath, Jessey; Behera, Ranjan; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Sciotti, Richard J.; Mensa-Wilmot, Kojo; Pollastri, Michael P.
Target repurposing is a proven method for finding new lead compounds that target Trypanosoma brucei, the causative agent of human African trypanosomiasis. Due to the recent discovery of a lapatinib-derived analog 2 with excellent potency against T. brucei (EC50 = 42 nM) and selectivity over human host cells, we have explored other classes of human tyrosine kinase inhibitor scaffolds in order to expand the range of chemotypes for pursuit. Following library expansion, we found compound 11e to have an EC50 of 84 nM against T. brucei cells while maintaining selectivity over human hepatocytes. In addition, the library was tested against causative agents of Chagas’ disease, leishmaniasis, and malaria. Two analogs with sub-micromolar potencies for T. cruzi (4j) and Plasmodium falciparum (11j) were discovered, along with an analog with considerable potency against Leishmania major amastigotes (4e). Besides identifying new and potent protozoan growth inhibitors, these data highlight the value of concurrent screening of a chemical library against different protozoan parasites. PMID:25685309
Torrie, Leah S; Wyllie, Susan; Spinks, Daniel; Oza, Sandra L; Thompson, Stephen; Harrison, Justin R; Gilbert, Ian H; Wyatt, Paul G; Fairlamb, Alan H; Frearson, Julie A
In the search for new therapeutics for the treatment of human African trypanosomiasis, many potential drug targets in Trypanosoma brucei have been validated by genetic means, but very few have been chemically validated. Trypanothione synthetase (TryS; EC 184.108.40.206; spermidine/glutathionylspermidine:glutathione ligase (ADP-forming)) is one such target. To identify novel inhibitors of T. brucei TryS, we developed an in vitro enzyme assay, which was amenable to high throughput screening. The subsequent screen of a diverse compound library resulted in the identification of three novel series of TryS inhibitors. Further chemical exploration resulted in leads with nanomolar potency, which displayed mixed, uncompetitive, and allosteric-type inhibition with respect to spermidine, ATP, and glutathione, respectively. Representatives of all three series inhibited growth of bloodstream T. brucei in vitro. Exposure to one of our lead compounds (DDD86243; 2 x EC(50) for 72 h) decreased intracellular trypanothione levels to <10% of wild type. In addition, there was a corresponding 5-fold increase in the precursor metabolite, glutathione, providing strong evidence that DDD86243 was acting on target to inhibit TryS. This was confirmed with wild-type, TryS single knock-out, and TryS-overexpressing cell lines showing expected changes in potency to DDD86243. Taken together, these data provide initial chemical validation of TryS as a drug target in T. brucei.
Lorente, Silvia Orenes; Rodrigues, Juliany C. F.; Jiménez, Carmen Jiménez; Joyce-Menekse, Miranda; Rodrigues, Carlos; Croft, Simon L.; Yardley, Vanessa; de Luca-Fradley, Kate; Ruiz-Pérez, Luis M.; Urbina, Julio; de Souza, Wanderley; Pacanowska, Dolores González; Gilbert, Ian H.
This paper describes the design and evaluation of novel azasterols as potential compounds for the treatment of leishmaniasis and other diseases caused by trypanosomatid parasites. Azasterols are a known class of (S)-adenosyl-l-methionine: Δ24-sterol methyltransferase(24-SMT) inhibitors in fungi, plants, and some parasitic protozoa. The compounds prepared showed activity at micromolar and nanomolar concentrations when tested against Leishmania spp. and Trypanosoma spp. The enzymatic and sterol composition studies indicated that the most active compounds acted by inhibiting 24-SMT. The role of the free hydroxyl group at position 3 of the sterol nucleus was also probed. When an acetate was attached to the 3β-OH, the compounds did not inhibit the enzyme but had an effect on parasite growth and the levels of sterols in the parasite, suggesting that the acetate group was removed in the organism. Thus, an acetate group on the 3β-OH may have application as a prodrug. However, there may be an additional mode(s) of action for these acetate derivatives. These compounds were shown to have ultrastructural effects on Leishmania amazonensis promastigote membranes, including the plasma membrane, the mitochondrial membrane, and the endoplasmic reticulum. The compounds were also found to be active against the bloodstream form (trypomastigotes) of Trypanosoma brucei rhodesiense, a causative agent of African trypanosomiasis. PMID:15273104
Brown, Anthony L.
Numerous scholars have illustrated how African American teachers' past experiences provide them a philosophical vision committed to teaching for social and educational change for African American students. This article draws from this body of work by looking at the diverse ways five African American male teachers used their past experiences to…
Brooks Greaux, Lisa
Even in an era when the country elected an African American man as President of the United States, there is still a paucity of African American women executives within Fortune 500 companies. Although more African American women have joined the ranks of corporate management over the last two decades, the numbers, when compared to those of White…
Malande, Oliver Ombeva
Helicobacter pylori gastritis infection rate increases with age. Higher rates have however been reported among young people in the developing countries of the world. The infection however has rarely been reported in infants, especially in Africa. This case series describes three cases of Helicobacter pylori gastritis infection as diagnosed in three infants. The goal is to raise the suspicion index of medical practitioners about the possibility of this this infection among infants who present with suggestive symptoms. On three separate occasions in 2012 and 2013, three ill, indigenous, black African female infants aged 4, 6 and 7 months, were brought to hospital with symptoms ranging from fever, refusal to feed, diarrhoea, restlessness, vomiting and irritability. In each case, systemic examination findings were unremarkable. After several laboratory investigations, each infant was found to have Helicobacter pylori infection following positive blood antibody (using Tell Me Fast H. Pylori antibody serum and Plasma test manufactured by Biocan Diagnostics Canada) and fecal HpSA ImmunoCardSTAT antigen tests. Repeat stool antigen test was negative in each case after completion of the recommended triple therapy. Helicobacter pylori infection has been rarely reported among infants. This case series highlights the need for health care providers to have a high index of suspicion so that infants with suggestive symptoms, especially in settings with high Helicobacter pylori colonization prevalence can be evaluated for Helicobacter pylori gastritis infection.
Otieno, Iddah Aoko
This case study uses post-colonial and dependency theoretical lenses to investigate the forces influencing policy, procedures, and participation in international activity in the post-colonial African university environment of Kenya's first national public university-the University of Nairobi (UoN). The research addresses (1) the approaches and…
Studman, Cliff; Tsheko, G. Nnunu
The impact of change strategies for developing research at an African primarily undergraduate institution is considered using a case study of the University of Botswana. After an analysis of the existing situation, a short research policy, written in understandable terms, was developed. The policy was structured so that it could be used for…
Milner, H. Richard
This case study sought to understand the nature of an African-American teacher's decision-making as she planned and enacted lessons. Findings suggest the teacher's cultural comprehensive knowledge was central in her thinking and decision-making. Future studies are encouraged. (Contains 2 figures and 25 footnotes.) (AUTHOR)
Jimes, Cynthia; Weiss, Shenandoah; Keep, Renae
This article presents a case study of the adoption and use of open textbooks by three high school teachers in the KwaZulu-Natal province of South Africa. The textbooks, collaboratively authored and distributed through the South African initiative, Siyavula, are available online and are openly licensed, allowing teachers to freely use, modify,…
Using case study methodology (Stake, 2006), this research examined the environmental influences, or contextual supports and barriers, that were most influential in contributing to African American students' persistence in an engineering major. Social cognitive career theory provides the framework for understanding the role of contextual supports…
Pépin, J.; Khonde, N.; Maiso, F.; Doua, F.; Jaffar, S.; Ngampo, S.; Mpia, B.; Mbulamberi, D.; Kuzoe, F.
OBJECTIVE: A randomized controlled trial was conducted to determine whether 7 days of intravenous eflornithine (100 mg/kg every 6 h) was as effective as the standard 14-day regimen in the treatment of late-stage Trypanosoma brucei gambiense trypanosomiasis. METHODS: A total of 321 patients (274 new cases, 47 relapsing cases) were randomized at four participating centres in Congo, Côte d'Ivoire, the Democratic Republic of the Congo, and Uganda to one of these treatment regimens and followed up for 2 years. RESULTS: Six patients died during treatment, one of whom was on the 7-day regimen, whereas the other five had been on the 14-day regimen (P = 0.2). The response to eflornithine differed markedly between Uganda and other countries. Among new cases in Uganda, the 2-year probability of cure was 73% on the 14-day course compared with 62% on the 7-day regimen (hazard ratio (HR) for treatment failure, 7-day versus 14-day regimen: 1.45, 95% CI: 0.7, 3.1, P = 0.3). Among new cases in Côte d'Ivoire, Congo, and the Democratic Republic of the Congo combined, the 2-year probability of cure was 97% on the 14-day course compared with 86.5% on the 7-day regimen (HR for treatment failure, 7-day vs 14-day: 6.72, 95% confidence interval (CI): 1.5, 31.0, P = 0.003). Among relapsing cases in all four countries, the 2-year probability of cure was 94% with 7 days and 100% with 14 days of treatment. Factors associated with a higher risk of treatment failure were: a positive lymph node aspirate (HR 4.1; 95% CI: 1.8-9.4), a cerebrospinal fluid (CSF) white cell count > or = 100/mm3 (HR 3.5; 95% CI: 1.1-10.9), being treated in Uganda (HR 2.9; 95% CI: 1.4-5.9), and CSF trypanosomes (HR 1.9; 95% CI: 0.9-4.1). Being stuporous on admission was associated with a lower risk of treatment failure (HR 0.18; 95% CI: 0.02-1.4) as was increasing age (HR 0.977; 95% CI: 0.95-1.0, for each additional year of age). DISCUSSION: The 7-day course of eflornithine is an effective treatment of relapsing cases
Beiler, Jessica S. B.; Zhu, Kangmin; Hunter, Sandra; Payne-Wilks, Kathleen; Roland, Chanel L.; Chinchilli, Vernon M.
Menstrual characteristics may serve as surrogate measures of endogenous estrogen and may be related to breast cancer risk. No previous studies have systematically investigated menstrual factors in relation to the disease in African-American women. This case-control study is aimed to assess the relationship between menstrual factors and breast cancer in African-American women. Cases were 304 African-American women, aged 20-64 living in three Tennessee counties, diagnosed with breast cancer between 1995 and 1998. Controls were selected through random-digit dialing and frequency matched to cases (n=305). Phone interviews were conducted on menstrual factors--age at menarche, time to regularity, cycle length, flow length, age at menopause--and other risk factors. Logistic regression showed that compared to women with short cycle length (<28 days), women with average cycle length > or =28 had decreased risk of breast cancer (odds ratio (OR)=0.60, 95% confidence interval (CI), 0.38-0.94). Dose-response analyses showed decreasing risk with longer cycle length. Results by menopausal status revealed an inverse relationship was shown only in postmenopausal women. No significant associations were observed for other menstrual factors. Findings suggest that cycle length has an inverse association with breast cancer in African-American women that may primarily exist for post-menopausal tumors. PMID:14620704
Smith, Felicia R.
This qualitative intrinsic case study was designed to assist Caucasian educators with the researched academic skills and behaviors to engage African-American females in the learning environment. The study provided strategies and recommendations to promote self-worth, self-motivation, self-efficacy, and morale in African-American females when they…
Obanda, V; Poghon, J; Yongo, M; Mulei, I; Ngotho, M; Waititu, K; Makumi, J; Gakuya, F; Omondi, P; Soriguer, R C; Alasaad, S
Tuberculosis is emerging/re-emerging in captive elephant populations, where it causes morbidity and deaths, although no case of TB in wild African elephants has been reported. In this paper we report the first case of fatal TB in an African elephant in the wild. The infection with Mycobacterium tuberculosis was confirmed by post-mortem and histological examinations of a female sub-adult elephant aged >12 years that died in Tsavo East National Park, Kenya, while under treatment. This case is unique in that during its lifetime the elephant had contact with both humans and wild elephants. The source of the infection was unclear because the elephant could have acquired the infection in the orphanage or in the wild. However, our results show that wild elephants can maintain human TB in the wild and that the infection can be fatal.
Canine leishmaniasis and American trypanosomiasis (AT) are caused by related hemoflagellated parasites, Leishmania spp. and Trypanosoma cruzi, which share several common host species. Dogs are reservoirs for human infections with both pathogens. We determined the prevalence of antibodies to Leishman...
The concept of 'vulnerability' is well established within the realm of research ethics and most ethical guidelines include a section on 'vulnerable populations'. However, the term 'vulnerability', used within a human research context, has received a lot of negative publicity recently and has been described as being simultaneously 'too broad' and 'too narrow'. The aim of the paper is to explore the concept of research vulnerability by using a detailed case study - that of mineworkers in post-apartheid South Africa. In particular, the usefulness of Kipnis's taxonomy of research vulnerability will be examined. In recent years the volume of clinical research on human subjects in South Africa has increased significantly. The HIV and TB pandemics have contributed to this increase. These epidemics have impacted negatively on the mining industry; and mining companies have become increasingly interested in research initiatives that address these problems. This case study explores the potential research vulnerability of mineworkers in the context of the South African mining industry and examines measures that can reduce this vulnerability.
Dawson, Dawnay Ardrean
The purpose of this study was to examine leadership practices that lead to improving academic achievement for African American males. Specifically, this study examined cultural insensitivity and its impact on educating African American male students in reading. The study utilized several techniques to determine what practices educators used to…
Bagwell, Cynthia S.
This study utilized a mixed methods design to analyze the ways in which teachers and African American families establish home-school partnerships, and to identify the beliefs, practices, and traditions of teachers and African American families that underlie such partnerships, the factors that motivate their development, and the ways these vary by…
Le, Yen; Holmes, Nancy C.
We present an exploratory study of the recreational behaviors, preferences, and opinions of African Americans in the Columbia, South Carolina area and identify potential barriers to visiting Congaree National Park. Focus groups with African American residents of the Columbia South Carolina area revealed that inadequate information, detachment from…
Stringer, Eddy W., III.
Data suggests that a significant loss of African American students from STEM majors occur between their freshmen and sophomore year. This attrition corresponds to the time period when students encounter the calculus sequence. For this reason, calculus persists as a serious barrier preventing African American students from entering STEM fields.…
Mbelesso, P; Mbadingaï, S; Laghoe Nguembe, G L S
Sleeping sickness is more prevalent in three historical regions of Central African Republic. Control measures were organized by the colonial authorities through health services to fight against this disease and other major diseases. Multivariate analysis and the government helped in controlling the disease in the focus of Nola-Bilolo, which was formerly hyperendemic. The authors report the results of the control measures that resulted in the extinction of the disease in this outbreak. This is a retrospective study from 1991 to 2008, and the data were collected from the National Program to fight against human African trypanosomiasis in Bangui and in the diagnostic and treatment center of Nola. It was highly endemic, with more than 300 cases recorded in the year 1991. The average number of cases was 200.8 per year between 1992 and 1998. Less than 50 cases per year were recorded from 2000 to 2006, and no cases have been detected since 2007. 69.35% of the patients were actively screened. 5,000 conical deltamethrin-impregnated traps (Gouteux and Lancien) had been used in 15 districts in the city of Nola and 46 surrounding villages by 20 trappers fully supported by the program. This is an example of regular active mass screening. Systematic treatment of detected cases and well-conducted vector control measures give hope to the affected populations to live peacefully in order to contribute to the development of their country.
AD-A280 198 I~hhumhhII AD_____ GRANT NO: DAMD17-90-Z-0005 (]’) TITLE: DIAGNOSIS AND CHEMOTHERAPY OF HUMAN TRYPANOSOMIASIS AND VECTOR ECOLOGY OF RIFT...Date OCONUS JUN 89 Diagnosis and Chemotherapy of Human Trypanosomiasis and Vector Ecology of Rift Valley Fever and Congo-Crimean Hemorrhagic Fever in...Kenya CONTENTS I. HUMAN TRYPANOSOMIASIS IN KENYA: DIAGNOSIS AND CHEMOTHERAPY Background
Moray, C; Game, E T; Maxted, N
Conserving crop wild relatives (CWR) is critical for maintaining food security. However, CWR-focused conservation plans are lacking, and are often based on the entire genus, even though only a few taxa are useful for crop improvement. We used taxonomic and geographic prioritisation to identify the best locations for in situ conservation of the most important (priority) CWR, using African cowpea (Vigna unguiculata (L.) Walp.) as a case study. Cowpea is an important crop for subsistence farmers in sub-Saharan Africa, yet its CWR are under-collected, under-conserved and under-utilised in breeding. We identified the most efficient sites to focus in situ cowpea CWR conservation and assessed whether priority CWR would be adequately represented in a genus-based conservation plan. We also investigated whether priority cowpea CWR are likely to be found in existing conservation areas and in areas important for mammal conservation. The genus-based method captured most priority CWR, and the distributions of many priority CWR overlapped with established conservation reserves and targets. These results suggest that priority cowpea CWR can be conserved by building on conservation initiatives established for other species.
Economic Community of West African States Monitoring Group as a Case Study Approved by: , Thesis Committee Chair Bruce W. Menning...also goes to my committee chairman, Dr. Bruce W. Menning, who gave me the needed encouragement from the very start and continued to the end. Despite...Mutual Assistance on Defence MODEL Movement for Democracy in Liberia MPCI Patriotic Movement of Côte d’ Iviore NATO North Atlantic Treaty
Galactionova, Katya; Tediosi, Fabrizio; de Savigny, Don; Smith, Thomas; Tanner, Marcel
Scale-up of malaria preventive and control interventions over the last decade resulted in substantial declines in mortality and morbidity from the disease in sub-Saharan Africa and many other parts of the world. Sustaining these gains will depend on the health system performance. Treatment provides individual benefits by curing infection and preventing progression to severe disease as well as community-level benefits by reducing the infectious reservoir and averting emergence and spread of drug resistance. However many patients with malaria do not access care, providers do not comply with treatment guidelines, and hence, patients do not necessarily receive the correct regimen. Even when the correct regimen is administered some patients will not adhere and others will be treated with counterfeit or substandard medication leading to treatment failures and spread of drug resistance. We apply systems effectiveness concepts that explicitly consider implications of health system factors such as treatment seeking, provider compliance, adherence, and quality of medication to estimate treatment outcomes for malaria case management. We compile data for these indicators to derive estimates of effective coverage for 43 high-burden Sub-Saharan African countries. Parameters are populated from the Demographic and Health Surveys and other published sources. We assess the relative importance of these factors on the level of effective coverage and consider variation in these health systems indicators across countries. Our findings suggest that effective coverage for malaria case management ranges from 8% to 72% in the region. Different factors account for health system inefficiencies in different countries. Significant losses in effectiveness of treatment are estimated in all countries. The patterns of inter-country variation suggest that these are system failures that are amenable to change. Identifying the reasons for the poor health system performance and intervening to tackle
Quijano-Hernández, Israel A; Castro-Barcena, Alejandro; Barbabosa-Pliego, Alberto; Ochoa-García, Laucel; Del Ángel-Caraza, Javier; Vázquez-Chagoyán, Juan C
American trypanosomiasis is a growing health issue in the Americas. México is an endemic country, where some locations such as in the State of México are considered highly prevalent. In the valley of Toluca city, the capital of the State of Mexico, there exists an apparent high prevalence in dogs. The absence of triatomine vectors suggests that dogs may not be infected. Therefore, we conducted a directed survey to domiciliated and nondomiciliated dogs to reassess dogs' T. cruzi seroprevalence status. HAI and ELISA serologic tests were applied to 124 and 167 serums of domiciliated and nondomiciliated dogs in the target city. Risk factors were estimated, but the results did not show any evidence to assess them. No domiciliated dogs tested positive to both tests, whereas only one non-domiciliated dog resulted positive. This animal may have acquired the infection in an endemic area and then migrated to Toluca. Research results indicate that T. cruzi infection is not actively transmitted among dogs, and it is pointed out that dogs are the main sentinel animal population to evaluate a possible expansion of the territory affected by Chagas' disease.
Trypanosomiasis, a group of diseases including sleeping sickness in humans and Nagana in cattle in Africa, and Chagas' disease in South America, remains a considerable problem in the 21(st) century. The therapies that are available, however, usually have their roots in the "dye therapy" of a century ago, knowledge gained at the microscope from parasite staining procedures and converted to chemotherapy based on compounds closely related to the laboratory reagents. Dyes such as trypan red and trypan blue led to the development of suramin, while cationic nitrogen heterocyclic dyes furnished examples of the phenanthridinium class, such as ethidium (homidium) and isometamidium. Both suramin and isometamidium remain in use. Owing to mutagenicity issues, the presence of ethidium among the phenanthridinium dyes has led to concerns over the clinical use of related derivatives. There are several mechanisms for dye-DNA interaction, however, including possible hydrogen bonding of dye to the polymer, and these are discussed together with structure-activity relations and cellular localization of the phenanthridine and isomeric acridines involved. Better understanding of nucleic acid binding properties has allowed the preparation of more effective phenanthridinium analogues intended for use as anticancer/antiviral therapy.
Murata, Yumie; Yonezawa, Takahiro; Kihara, Ichiro; Kashiwamura, Toshihide; Sugihara, Yuji; Nikaido, Masato; Okada, Norihiro; Endo, Hideki; Hasegawa, Masami
Despite vigorous genetic studies of African elephants (Loxodonta africana and L. cyclotis) during the last decade, their evolutionary history is still obscure. Phylogenetic studies and coalescence time estimation using longer nucleotide sequence data from denser samplings are necessary to better understand the natural history of African elephants. Further, species identification among African elephants is sometimes very difficult using only the external morphological characteristics. This is a serious problem for making an adequate breeding plan in zoological gardens. In this paper, we investigated the continent-wide phylogeographical pattern of the African elephants and estimated the coalescence times among them. From these molecular data and geological evidence, we proposed an evolutionary scenario for the African elephants. We further demonstrated the effectiveness of molecular phylogenetic methods in species identification.
Castillo-Garit, Juan Alberto; Abad, Concepción; Rodríguez-Borges, J Enrique; Marrero-Ponce, Yovani; Torrens, Francisco
The neglected tropical diseases (NTDs) affect more than one billion people (one-sixth of the world's population) and occur primarily in undeveloped countries in sub-Saharan Africa, Asia, and Latin America. Available drugs for these diseases are decades old and present an important number of limitations, especially high toxicity and, more recently, the emergence of drug resistance. In the last decade several Quantitative Structure-Activity Relationship (QSAR) studies have been developed in order to identify new organic compounds with activity against the parasites responsible for these diseases, which are reviewed in this paper. The topics summarized in this work are: 1) QSAR studies to identify new organic compounds actives against Chaga's disease; 2) Development of QSAR studies to discover new antileishmanial drusg; 3) Computational studies to identify new drug-like compounds against human African trypanosomiasis. Each topic include the general characteristics, epidemiology and chemotherapy of the disease as well as the main QSAR approaches to discovery/identification of new actives compounds for the corresponding neglected disease. The last section is devoted to a new approach know as multi-target QSAR models developed for antiparasitic drugs specifically those actives against trypanosomatid parasites. At present, as a result of these QSAR studies several promising compounds, active against these parasites, are been indentify. However, more efforts will be required in the future to develop more selective (specific) useful drugs.
Ranjithkumar, Muthusamy; Malik, Tauseef Ahmed; Saxena, Anju; Dan, Ananya; Sakthivel, Pillanatham Civalingam; Dey, Sahadeb
Trypanosomiasis caused by Trypanosoma evansi commonly produces wasting disease with signs of emaciation and cachexia mainly at the end stage. The present study was conducted to explore the possible hyperlipaemia or hyperlipidaemia and its association with cachexia-anorexia in equine trypanosomiasis. Out of the fifteen confirmed animals, none of the plasma sample was opaque. There was a significant increase in plasma triglyceride, total cholesterol and blood urea nitrogen and a highly significant increase in low-density lipoprotein (LDL) levels. A mild increase in high-density lipoprotein (HDL) and very low-density lipoprotein levels were observed, while the relative percentage of HDL and LDL was altered with high significance. A moderate increase in triglyceride and highly significant increase in LDL might be the reasons for retention of appetite and lipolysis. Possible protein breakdown and presence of lipolysis might be the reasons for cachexia in equine trypanosomiasis.
Ohaeri, C C; Eluwa, M C
Blood samples were collected from 46 domestic ruminants comprising of 23 trypanosomiasis infected and 23 uninfected control groups to study some biochemical and haematological effects of trypanosomiasis under natural condition. The effect of trypanosome infection in ruminant animals showed that infected animals had significantly lower (P<0.05) packed cell volume, erythrocyte count and higher (P<0.01) mean cell volumes than uninfected animals. Leucocytosis, reticulocytosis and thrombocytopenia were also observed. The infection also produced a decrease in albumin (P<0.001), significant increase in total protein and bilirubin levels. These changes were not seen in the animals that were not infected. The outcome of the work shows that herds are severely affected by the disease, and therefore supports the prospect of routine check as an epidemiologic tool in trypanosomiasis based on its abnormal effects in blood.
Coetzee, Stephen A.; Janse van Rensburg, Cecile; Schmulian, Astrid
This study explores differences in students' reading comprehension of International Financial Reporting Standards in a South African financial reporting class with a heterogeneous student cohort. Statistically significant differences were identified for prior academic performance, language of instruction, first language and enrolment in the…
Seale, Oliver; Cross, Michael
In recent years, deanship in universities has become more complex and challenging. Deans in South African universities take up their positions without appropriate training and prior executive experience, and with no clear understanding of the ambiguity and complexity of their roles. This paper calls for appropriate leadership development…
Darboe, Kebba; Ahmed, Lul S.
Needs assessment is the process of identifying the gap between a target population's needs and its services. If a gap exists, a program can be designed to effectively respond to those needs. This article explores the needs of elderly African immigrants in Minnesota through the use of qualitative interviews. A convenience sampling was used to…
Ormerod, Beverly; And Others
Reports on a computerized statistical study of discourse bias and the specificity of female writing against male writing. Examines the characters in 20 novels written by male and female Francophone African authors. Finds a number of significant differences that characterize the make-up of novels by the two sexes. (CFR)
Marbley, Aretha Faye; Wimberly, Cynthia; Berg, Rachelle; Rouson, Leon; Wilkins, Erica
Using the lessons learned from mistakes made in their earlier clinical work with African American families, through the lens of Multicultural Counseling and Therapy theory, these culturally diverse practitioners use reflections from their counseling experiences to offer clinicians a people-responsive, diversity-sensitive framework and provide…
Knuth, Carole Brown
Three books by Eleanora Tate, "The Secret of Gumbo Grove" (1988), "Thank You, Dr. Martin Luther King, Jr.!" (1992), and "A Blessing in Disguise" (1995) are discussed with respect to their portrayal of African-American children and their responsibility to both themselves and their community. (MAK)
De Villiers, Rian
The United Kingdom (particularly England) is the main developed country that recruits teachers from South Africa. This article provides an overview of teacher migration from South Africa to the United Kingdom over the past decade. The research focuses on the following aspects of migration: the recruitment of South African teachers; motivation for…
Dahl, Anthony G.
Discusses growing enrollments in foreign languages at Spelman College, a small language arts college for African American women in Atlanta, Georgia. Attributes the growing enrollments to the willingness of faculty to attend to student needs, interests, and specific black heritage. Suggests strategies for attracting students of color to languages…
This paper provides a background to recent developments in language planning in South Africa. Following a historical review, it focuses on a Bill of Rights in the new constitution which has, since 1993, demanded a shift towards rights-based language policy within a liberal framework. Debates within the Pan South African Language Board (PANSALB)…
Carmody, John; Misra, Raghunath P; Langford, Marlyn P; Byrd, William A; Ditta, Lauren; Vekovius, Bryan; Texada, Donald E
A case of sporadic Burkitt lymphoma (sBL) presenting with jaw and lid involvement in a diabetic adult African American female and a review of adult orbital Burkitt lymphoma cases are presented. Lid edema, visual loss, ophthalmoparesis, proptosis, and sinusitis progressed over 4 weeks despite antibiotic and steroid treatment. Upper lid biopsy histopathological evaluation and immunophenotyping revealed a homogenous mass of atypical CD10 and CD20-negative B-cells and tingible body macrophages yielding a “starry sky” appearance. Cytogenetic analysis detected a minor variant c-MYC translocation, but no Epstein–Barr virus RNA. Detection of multiple lesions prompted a diagnosis of stage IV disease that totally regressed following radiation and chemotherapy. Review results of the six adult orbital sBL cases support a poor prognosis and a heightened suspicion of variant CD10, CD20 and BCL6 positive sBL in adults presenting with jaw pain and rapidly progressive orbital symptoms, particularly in female, African American, and diabetic patients. PMID:21573040
Rollnick, Marissa; Bennett, Judith; Rhemtula, Mariam; Dharsey, Nadine; Ndlovu, Thandi
This paper presents two South African case studies designed to explore the influence of subject matter knowledge on pedagogical content knowledge (PCK). In the first case study on teaching the mole in two township schools, the findings illustrate that the participant teachers favoured procedural approaches at the expense of conceptual…
Froeschl, Guenter; Kayembe, Pitchou Kasongo
Cases of monkeypox in humans are frequently reported from the Democratic Republic of Congo. The few reports from the Central African Republic have been limited to cases in the far South closely bordering the Congos. Team members of an international medical organisation have suspected clinically two human cases of MPX, associated with clinical signs of coagulopathy and haemorrhage in the North of the country. Key findings were history of a squirrel, fever and vesicular dermal eruptions. Subsequently patients developed profuse epistaxis and hematemesis, associated with clinical signs of shock. Both patients were isolated and treated symptomatically. Samples were sent to a regional reference laboratory, who initially issued a confirmation of the suspected diagnosis of MPX in both cases. The result was later revised, and additional analyses of samples could not confirm the diagnosis. PMID:26664524
Cavan, Gina; Lindley, Sarah; Kibassa, Deusdedit; Shemdoe, Riziki; Capuano, Paolo; De Paola, Francesco; Renner, Florian; Pauleit, Stephan
Urban green structure provides important regulating ecosystem services, such as temperature and flood regulation, and thus, has the potential to increase the resilience of African cities to climate change. Green structures within urban areas are not only limited to discrete units associated with recreational parks, agricultural areas and open spaces: they also exist within zones which have other primary functions, such as church yards, along transport routes, and within residential areas. Differing characteristics of urban areas can be conceptualised and subsequently mapped through the idea of urban morphology types. Urban morphology types are classifications which combine facets of urban form and function. When mapped, UMT units provide biophysically relevant meso-scale geographical zones which can be used as the basis for understanding climate-related impacts and adaptations. For example, they support the assessment of urban temperature patterns and the temperature regulating services provided by urban green structures. There are some examples of the use of UMTs for assessing regulating ecosystem services in European cities but little similar knowledge is available in an African context. This paper outlines the concept of urban morphology types (UMTs) and how they were applied to African case study cities (Cavan et al., 2012). It then presents the methods used to understand temperature regulating ecosystem services across an example African case study city, including (i) a GIS-based assessment of urban green structures, and (ii) applying an energy balance model to estimate current and future surface temperatures under climate change projections. The assessment is carried out for Dar es Salaam, Tanzania. Existing evidence suggests increases in both mean and extreme temperatures in the city. Historical analysis of the number of hot days per year suggests a rise from a maximum of 47 days per year in the period 1961-87 to 72 days per year in 2003-2011 (Giugni et al
Whiters, David L; Santibanez, Scott; Dennison, David; Clark, H Westley
This case study examined programmatic data from a federally funded faith-based rapid HIV testing initiative. In 2004, Recovery Consultants of Atlanta, Inc. (RCA, Inc.) began providing rapid HIV testing in collaboration with six Atlanta-based African-American churches. Of the 1,947 persons tested from January 2004 to July 2005, 1,872 (96.1%) were African-American, 1,247 (64%) were male, and 1,612 (82.8%) were between the age of 26 and 56. A total of 85 HIV-infected individuals were identified and 72 were identified as previously undiagnosed cases (positivity rate of 3.7%). This case study highlights and promotes rapid HIV testing offered in partnership with African American churches as a strategy for raising HIV awareness among inner-city substance users.
Mahmoud, M M; Elmalik, K H
Experimental Trypanosoma congolense infections of goats and calves were compared. Goats developed a chronic form of trypanosomiasis, often recovering spontaneously from a strain which caused an acute fatal disease in calves. Goats may be important in the maintenace of T. congolense in nature in the Sudan.
Cossic, Brieuc G A; Adjahoutonon, Brice; Gloaguen, Pierre; Dibanganga, Gui Lov; Maganga, Gael; Leroy, Pascal; MacLeod, Ewan T; Picozzi, Kim
A longitudinal study was conducted within a cattle ranch in Gabon to determine the diminazene aceturate (Berenil) index (DAI) in a group of Zebu, raised under low tsetse density; this measure providing an assessment of trypanosomiasis risk. The objective was to evaluate the trypanosomiasis pressure thus informing trypanosomiasis control methods and cattle management. Twenty female adult Zebu were monitored for 24 weeks during the dry season. Blood samples were collected on a weekly basis and subjected to parasitological and haematological analysis (n = 480), using the buffy-coat method and the packed cell volume value (PCV), respectively, infected animals were treated with a single intramuscular injection of diminazene aceturate (8 mg/kg). Twenty-nine single infectious events were recorded and a DAI of 1.45 was calculated. Two trypanosome species were identified: Trypanosoma congolense (96.2%) and Trypanosoma vivax (3.8%). The mean PCV value of the infected animals was lower (26.6) compared to non-infected animals (32.0). This study shows that DAI may be a useful tool to assess trypanosomiasis. However, this is a time-consuming method that may be improved by using randomly selected sentinel animals to adapt the chemoprophylactic schemes, hence decreasing the costs and the drug resistance risk.
Whitfield, A K
Estuaries are well known for their role as nutrient and detrital sinks that stimulate high levels of both primary and secondary production which, in turn, support a large biomass of fishes per unit area. This study reviews available information on coastal fish biomasses (g m(-2) wet mass) and productivity (g m(-2) wet mass year(-1) ) in order to place South African data on these topics into a global perspective. Using biogeographic fish productivity estimates, together with estuarine water area, the approximate annual teleost production in South African estuaries was calculated at 585, 1706 and 13 904 t in the cool temperate, warm temperate and subtropical regions, respectively. Total annual fish production in estuaries on the subcontinent is conservatively estimated at 16 195 t, but this figure is likely to fluctuate widely, depending on recruitment success and annual environmental conditions pertaining to these systems. Approximately 2000 t of fish are estimated to be harvested by fishing activities in South African estuaries each year, which represents c. 12% of annual fish production. Although this figure may appear sustainable, the reality is that there are a few heavily targeted estuary-associated marine species at the top of the food chain that are being overexploited by both anglers and subsistence fishermen. Natural mortalities due to piscivorous fish and bird predation has been estimated at c. 3% of total fish biomass per month in the East Kleinemonde Estuary, but this figure will vary considerably depending on bird abundance and foraging patterns along the coast. In contrast to catches made by the fishermen, piscivorous fishes and birds are targeting mainly juvenile marine fish and small estuarine resident species that are very abundant and generally low down in the food web.
Pinheiro, Thiago Pastor da Silva; Carneiro, José Thiers; de Melo Alves, Sérgio; de Jesus Viana Pinheiro, João; Tuji, Fabrício Mesquita
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare condition that occurs normally in the anterior maxilla of infants aged <1 year. The use of clinical and imaging tools for MNTI is extremely important to prevent problems with function as well as the aesthetic features in a breastfeeding child. Brazil is a multiethnic country with a poor epidemiological policy and little data to track the incidence of certain diseases, including MNTI. It is important to study this pathology with ethnicity as a factor to improve the current epidemiological programs and establish better post-treatment management. This paper describes a case of a 2-month-old male of African-indigenous descent and Brazilian Amazon residency, who presented to our unit in 2009 with a history of an expanding mass involving the anterior maxilla. Clinical and computerized tomography scans were used to diagnose the mass as MNTI, which was removed by total excision. A biopsy later confirmed the MNTI diagnosis.
An African American male to female transgender patient treated with estrogen detected a breast lump that was confirmed by her primary care provider. The patient refused mammography and 14 months later she was diagnosed with metastatic breast cancer with spinal cord compression. We used ethnographic interviews and observations to elicit the patient’s conceptions of her illness and actions. The patient identified herself as biologically male and socially female; she thought that the former protected her against breast cancer; she had fears that excision would make a breast tumor spread; and she believed injectable estrogens were less likely than oral estrogens to cause cancer. Analysis suggests dissociation between the patient’s social and biological identities, fear and fatalism around cancer screening, and legitimization of injectable hormones. This case emphasizes the importance of eliciting and interpreting a patient’s conceptions of health and illness when discordant understandings develop between patient and physician. PMID:19898907
Malpeli, Katherine C.; Chirico, Peter G.
The Central African Republic (CAR), a country with rich diamond deposits and a tumultuous political history, experienced a government takeover by the Seleka rebel coalition in 2013. It is within this context that we developed and implemented a geospatial approach for assessing the lootability of high value-to-weight resource deposits, using the case of diamonds in CAR as an example. According to current definitions of lootability, or the vulnerability of deposits to exploitation, CAR's two major diamond deposits are similarly lootable. However, using this geospatial approach, we demonstrate that the deposits experience differing political geographic, spatial location, and cultural geographic contexts, rendering the eastern deposits more lootable than the western deposits. The patterns identified through this detailed analysis highlight the geographic complexities surrounding the issue of conflict resources and lootability, and speak to the importance of examining these topics at the sub-national scale, rather than relying on national-scale statistics.
Bm'niyat Bangamboulou-te-niya, D
Development is a complex phenomenon that concerns all the structures and subsystems of a society, affecting its quantitative aspects through economic growth and its qualitative aspects through social and cultural change. Planning is needed, but it is effective only to the extent that it is applied to a known and controllable reality. The integration of population and development is still a poorly defined concept despite the fat the it has been a topic of interest for the past several decades. at least since the 1946 creation of the UN Population Commission. Development planning should begin with evaluation of the past and present economic, social, and demographic situation of the country and should include formulation of clear objectives. The Central African Republic is a hugh country with some significant resources but a fragile and underdeveloped economy. The population, estimated at nearly 3 million, is very unevenly distributed, with 1/2 million living in the capital of Bangui. Fertility and mortality are high. The Central African Republic has had multi year development plans since 1948, but they have largely consisted of collections of projects funded by external investment. In the absence of institutional mechanisms capable of defining priorities and strategies leading to concrete decisions, the plans remained excessively general and ambitious. Economic planning has improved somewhat over the years, but there is still a lack of basic economic and social data, a shortage of financial resources, and inadequate mechanisms for setting priorities and strategies for decision making. No mechanism has been developed for integrating population and development although some research and family planning activities have been undertaken. A 1980 national seminar on problems of development was attended by representatives of all sectors, and in 1981 a national team formulated guidelines for a new strategy of social development. Family planning services were added to the
Gamble, Angie Monique
The purpose of this qualitative case study was to explore faculty diversity in the South by examining the campus climate and leadership commitment to the recruitment and retention of African American faculty. The Critical Race Theory (CRT) concept of storytelling captured the participants' personal experiences and perceptions. Three higher…
Kinyanda, Eugene; Hjelmeland, Heidi; Musisi, Seggane
Psychological factors associated with deliberate self-harm (DSH) as seen in an African population in Uganda are described. A case-control study design was employed in which a Luganda version (predominant language in the study area) of the modified European Parasuicide Interview Schedule I (EPSIS I) was used to collect data. The controls were…
Piazza-Bonin, Elizabeth; Neimeyer, Robert A; Burke, Laurie A; McDevitt-Murphy, Meghan E; Young, Amanda
Disenfranchised grief is experienced when a mourner's grief response is socially invalidated, unacknowledged, or discouraged. When the circumstances of death or the emotional reactions of the griever violate social norms, empathic failures can occur within the bereaved individual's support systems. This study used conventional content analysis, an intensive and inductive qualitative research method, to analyze the experience of one African American woman who lost her only son to homicide, a particularly distressing and marginalized form of loss. Results elucidate both the empathic failings and resiliencies within the social systems of this griever and emerged from the perspectives offered by the bereaved mother and her primary supporter. Clinical implications and suggestions for future research are discussed.
Health financing reforms in most low-income countries promote social and micro health insurance, in order to reduce direct spending by patients. Three phases of development can be distinguished in African countries: at first, schemes were developed only for the formal sector, then micro health insurance targeted the informal sector, and finally, health insurance was included in larger plans to reach universal coverage. The impact of health insurance is, as yet, difficult to assess. If beneficiaries have a better access to health services, the financing of health sector is not significantly improved, and there is no change in professional behaviour, in particular, in public facilities. In spite of their limits, social health insurance schemes continue to be implemented, but as a part of hybrid financing system, fitting with the abilities of low-income countries.
Okello, Anna L.; Bardosh, Kevin; Smith, James; Welburn, Susan C.
Background The recent emergence of zoonotic diseases such as Highly Pathogenic Avian Influenza (HPAI) and Severe Acute Respiratory Syndrome (SARS) have contributed to dominant Global Health narratives around health securitisation and pandemic preparedness, calling for greater co-operation between the health, veterinary and environmental sectors in the ever-evolving One Health movement. A decade later, One Health advocates face increasing pressure to translate the approach from theory into action. Methodology/Principal Findings A qualitative case study methodology was used to examine the emerging relationships between international One Health dialogue and its practical implementation in the African health policy context. A series of Key Informant Interviews (n = 32) with policy makers, government officials and academics in Nigeria, Tanzania and Uganda are presented as three separate case studies. Each case examines a significant aspect of One Health operationalisation, framed around the control of both emerging and Neglected Zoonotic Diseases including HPAI, Human African Trypanosomiasis and rabies. The research found that while there is general enthusiasm and a strong affirmative argument for adoption of One Health approaches in Africa, identifying alternative contexts away from a narrow focus on pandemics will help broaden its appeal, particularly for national or regionally significant endemic and neglected diseases not usually addressed under a “global” remit. Conclusions/Significance There is no ‘one size fits all’ approach to achieving the intersectoral collaboration, significant resource mobilisation and political co-operation required to realise a One Health approach. Individual country requirements cannot be underestimated, dismissed or prescribed in a top down manner. This article contributes to the growing discussion regarding not whether One Health should be operationalised, but how this may be achieved. PMID:24851901
Bertrand, E; Renambot, J; Chauvet, J; Seka, R; Ticolat, R; Odi Assamoi, M; Ndori, R; Ekra, A
The authors studied 31 cases of coronary artery disease with normal or minimally diseases coronary arteries in black Africans, 29.8% of 104 coronary patients undergoing coronary angiography in this series. These 31 cases comprised 16 cases of infarction, 10 cases of angina, 3 ventricular aneurysms and 2 cases of silent ischemia in diabetic patients. Twenty-five patients were men (80.6%). There were 6 women (19.3%) two of whom presented in the post-partum period. The average age of these patients was 45 years (males: 47.7 years; females: 41.8 years). The following risk factors were noted: smoking (60%), hypertension (25.8%), obesity (29%), diabetes (12.9%), serum cholesterol (average 2.15 g/l), serum triglycerides (average 1.25 g/l). The risk index per patient was 1.29. In comparison with coronary patients with angiographic coronary lesions (n = 73), the patients with normal angiography were significantly younger, comprised more females and had fewer risk factors (especially hypertension and diabetes), though this was not statistically significant. The prevalence of inaugural infarction was 81.2% in the cases of infarction with normal coronary arteries. These infarcts may be complicated by ventricular aneurysm formation. Spontaneous spasm was observed in 3 out of 31 patients (9.6%) at coronary angiography. A provocative test was performed in only 2 cases and 1 was positive. This deserves further study and may have therapeutic implications. The authors emphasise the high incidence of hemoglobin S or C traits (57.1%). These heterozygotic hemoglobinopathies could be a risk factor in these coronary patients with normal coronary angiography.
Lindsey, Peter A; Nyirenda, Vincent R; Barnes, Jonathan I; Becker, Matthew S; McRobb, Rachel; Tambling, Craig J; Taylor, W Andrew; Watson, Frederick G; t'Sas-Rolfes, Michael
Many African protected areas (PAs) are not functioning effectively. We reviewed the performance of Zambia's PA network and provide insights into how their effectiveness might be improved. Zambia's PAs are under-performing in ecological, economic and social terms. Reasons include: a) rapidly expanding human populations, poverty and open-access systems in Game Management Areas (GMAs) resulting in widespread bushmeat poaching and habitat encroachment; b) underfunding of the Zambia Wildlife Authority (ZAWA) resulting in inadequate law enforcement; c) reliance of ZAWA on extracting revenues from GMAs to cover operational costs which has prevented proper devolution of user-rights over wildlife to communities; d) on-going marginalization of communities from legal benefits from wildlife; e) under-development of the photo-tourism industry with the effect that earnings are limited to a fraction of the PA network; f) unfavourable terms and corruption which discourage good practice and adequate investment by hunting operators in GMAs; g) blurred responsibilities regarding anti-poaching in GMAs resulting in under-investment by all stakeholders. The combined effect of these challenges has been a major reduction in wildlife densities in most PAs and the loss of habitat in GMAs. Wildlife fares better in areas with investment from the private and/or NGO sector and where human settlement is absent. There is a need for: elevated government funding for ZAWA; greater international donor investment in protected area management; a shift in the role of ZAWA such that they focus primarily on national parks while facilitating the development of wildlife-based land uses by other stakeholders elsewhere; and new models for the functioning of GMAs based on joint-ventures between communities and the private and/or NGO sector. Such joint-ventures should provide defined communities with ownership of land, user-rights over wildlife and aim to attract long-term private/donor investment. These
AD-A259 524 AD GRANT NO: DAMD17-90-Z-0005 TITLE: DIAGNOSIS AND CHEMOTHERAPY OF HUMAN TRYPANOSOMIASIS AND VECTOR ECOLOGY OF RIFT VALLEY FEVER AND...62787A 62787A870 AN 014 11. TITLE (dud Secufity Claniflcat•)n) Diagnosis and Chemotherapy of Human Trypanosomiasis and Vector Ecology of Rift Valley...OCONUS JUN 89 - -- .- . . .- . . .. ’-..." -. . :- -•- ... , .-. ,. I Diagnosis and Chemotherapy of Human Trypanosomiasis a. Screening of WRAIR
Lindsey, Peter A.; Nyirenda, Vincent R.; Barnes, Jonathan I.; Becker, Matthew S.; McRobb, Rachel; Tambling, Craig J.; Taylor, W. Andrew; Watson, Frederick G.; t’Sas-Rolfes, Michael
Many African protected areas (PAs) are not functioning effectively. We reviewed the performance of Zambia’s PA network and provide insights into how their effectiveness might be improved. Zambia’s PAs are under-performing in ecological, economic and social terms. Reasons include: a) rapidly expanding human populations, poverty and open-access systems in Game Management Areas (GMAs) resulting in widespread bushmeat poaching and habitat encroachment; b) underfunding of the Zambia Wildlife Authority (ZAWA) resulting in inadequate law enforcement; c) reliance of ZAWA on extracting revenues from GMAs to cover operational costs which has prevented proper devolution of user-rights over wildlife to communities; d) on-going marginalization of communities from legal benefits from wildlife; e) under-development of the photo-tourism industry with the effect that earnings are limited to a fraction of the PA network; f) unfavourable terms and corruption which discourage good practice and adequate investment by hunting operators in GMAs; g) blurred responsibilities regarding anti-poaching in GMAs resulting in under-investment by all stakeholders. The combined effect of these challenges has been a major reduction in wildlife densities in most PAs and the loss of habitat in GMAs. Wildlife fares better in areas with investment from the private and/or NGO sector and where human settlement is absent. There is a need for: elevated government funding for ZAWA; greater international donor investment in protected area management; a shift in the role of ZAWA such that they focus primarily on national parks while facilitating the development of wildlife-based land uses by other stakeholders elsewhere; and new models for the functioning of GMAs based on joint-ventures between communities and the private and/or NGO sector. Such joint-ventures should provide defined communities with ownership of land, user-rights over wildlife and aim to attract long-term private/donor investment. These
Atawodi, S E; Ameh, D A; Ibrahim, S; Andrew, J N; Nzelibe, H C; Onyike, E O; Anigo, K M; Abu, E A; James, D B; Njoku, G C; Sallau, A B
A survey was carried out in Kaduna State of Nigeria to establish the indigenous knowledge system for treating trypanosomiasis in domestic animals. Questionnaire and interviews were, respectively, administered to, or conducted with about 200 livestock farmers and traders spread around the state. Data obtained revealed the use of several plants either alone or in combination, for the treatment and management of trypasonomiasis. The most common plants encountered were Adansonia digitata, Terminalia avicennoides, Khaya senegalensis, Cissus populnea, Tamarindus indica, Lawsonia inermis, Boswellia dalzielli, Pseudocedrela kotschi, Syzyium quinensis, Sterculia setigera, Afzelia africana, Prosopis africana, Lancea kerstingii. The method of preparation and mode of administration of some of these plants in the treatment of trypanosomiasis are reviewed and discussed.
Capewell, Paul; Cren-Travaillé, Christelle; Marchesi, Francesco; Johnston, Pamela; Clucas, Caroline; Benson, Robert A; Gorman, Taylor-Anne; Calvo-Alvarez, Estefania; Crouzols, Aline; Jouvion, Grégory; Jamonneau, Vincent; Weir, William; Stevenson, M Lynn; O'Neill, Kerry; Cooper, Anneli; Swar, Nono-raymond Kuispond; Bucheton, Bruno; Ngoyi, Dieudonné Mumba; Garside, Paul
The role of mammalian skin in harbouring and transmitting arthropod-borne protozoan parasites has been overlooked for decades as these pathogens have been regarded primarily as blood-dwelling organisms. Intriguingly, infections with low or undetected blood parasites are common, particularly in the case of Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. We hypothesise, therefore, the skin represents an anatomic reservoir of infection. Here we definitively show that substantial quantities of trypanosomes exist within the skin following experimental infection, which can be transmitted to the tsetse vector, even in the absence of detectable parasitaemia. Importantly, we demonstrate the presence of extravascular parasites in human skin biopsies from undiagnosed individuals. The identification of this novel reservoir requires a re-evaluation of current diagnostic methods and control policies. More broadly, our results indicate that transmission is a key evolutionary force driving parasite extravasation that could further result in tissue invasion-dependent pathology. DOI: http://dx.doi.org/10.7554/eLife.17716.001 PMID:27653219
Adebowale, Adekunle; Lamb, Jennifer; Nicholas, Ashley; Naidoo, Yougasphree
Recently developed computational tools in ITS2 sequence-structure phylogenetics are improving tree robustness by exploitation of the added information content of the secondary structure. Despite this strength, however, their adoption for species-level clarifications in angiosperms has been slow. We investigate the utility of combining ITS2 sequence and secondary structure to separate species of southern African Strychnos, and assess correlation between compensatory base changes (CBCs) and currently recognised species boundaries. Combined phylogenetic analysis of sequence and secondary structure datasets performed better, in terms of robustness and species resolution, than analysis involving primary sequences only, achieving 100 and 88.2 % taxa discriminations respectively. Further, the Strychnos madagascariensis complex is well-resolved by sequence-structure phylogenetic analysis. The 17 Strychnos species corresponded to 14 ITS2 CBC clades. Four of the five taxa in section Densiflorae belong to a single CBC clade, whose members tend to form natural hybrids. Our finding supports the application of ITS2 as a complementary barcoding marker for species identification. It also highlights the potential of comparative studies of ITS2 CBC features among prospective parental pairs in breeding experiments as a rapid proxy for cross compatibility assessment. This could save valuable time in crop improvement. Patterns of CBC evolution and species boundaries in Strychnos suggests a positive correlation. We conclude that the CBC pattern coupled with observed ITS2 sequence paraphyly in section Densiflorae points to a speciation work-in-progress.
Lubben, Fred; Sadeck, Melanie; Scholtz, Zena; Braund, Martin
This paper reports on a study into the untutored ability of Grade 10 students to engage in argumentation about the interpretation of experimental data, and the effect of unsupported small group discussions on this ability. In this study, argumentation intends to promote critical thinking. The sample includes 266 students from five South African schools across the resource spectrum, forming 70 friendship groups. Students are required to provide written interpretations of experimental data, and justify these interpretations based on the evidence and concepts of measurement. Individual responses form the basis of small group discussions after which students again provide written justified interpretations of the readings. The data show an initial low level of argumentation, with significant variation according to school resource levels. Considerable improvement in the level of argumentation occurs merely through small group discussions unsupported by the teacher. The findings suggest several factors influencing argumentation ability such as experience with practical work, perceptions of the purpose of small group discussions, the language ability to articulate ideas and cultural influences. Methodological issues arising from the study and implications for teaching and assessment are discussed.
Background The community case management of malaria (CCMm) is now an established route for distribution of artemisinin-based combination therapy (ACT) in rural areas, but the feasibility and acceptability of the approach through community medicine distributors (CMD) in urban areas has not been explored. It is estimated that in 15 years time 50% of the African population will live in urban areas and transmission of the malaria parasite occurs in these densely populated areas. Methods Pre- and post-implementation studies were conducted in five African cities: Ghana, Burkina Faso, Ethiopia and Malawi. CMDs were trained to educate caregivers, diagnose and treat malaria cases in < 5-year olds with ACT. Household surveys, focus group discussions and in-depth interviews were used to evaluate impact. Results Qualitative findings: In all sites, interviews revealed that caregivers' knowledge of malaria signs and symptoms improved after the intervention. Preference for CMDs as preferred providers for malaria increased in all sites. Quantitative findings: 9001 children with an episode of fever were treated by 199 CMDs in the five study sites. Results from the CHWs registers show that of these, 6974 were treated with an ACT and 6933 (99%) were prescribed the correct dose for their age. Fifty-four percent of the 3,025 children for which information about the promptness of treatment was available were treated within 24 hours from the onset of symptoms. From the household survey 3700 children were identified who had an episode of fever during the preceding two weeks. 1480 (40%) of them sought treatment from a CMD and 1213 of them (82%) had received an ACT. Of these, 1123 (92.6%) were administered the ACT for the correct number of doses and days; 773 of the 1118 (69.1%) children for which information about the promptness of treatment was available were treated within 24 hours from onset of symptoms, and 768 (68.7%) were treated promptly and correctly. Conclusions The concept of
Norman, Lashaunda Renea
This qualitative case study investigated the teaching strategies that improve science learning of African American students. This research study further sought the extent the identified teaching strategies that are used to improve African American science learning reflect culturally responsive teaching. Best teaching strategies and culturally…
Hessel, P.A.; Sluis-Cremer, G.K.; Hnizdo, E.
A case-control study was undertaken to assess the association between lung cancer and silicosis or silica dust exposure in white South African gold miners. Cases and controls were identified from deaths reported to the Gold Miners Provident Fund for the period January, 1979-October, 1983. Two controls were matched to each case by year of birth (+/- 2 years) and by smoking (+/- 5 cigarettes or equivalents per day) assessed 10 years (+/- 2 years) prior to death. One hundred thirty-three matched triplets were identified. The results showed no overall association between lung cancer and radiological silicosis (OR = 1.08, p = 0.92). Autopsy data indicated no overall associations between lung cancer and silicosis of the lung parenchyma (OR = 1.49, p = 0.11), the pleura (OR = 0.72, p = 0.30), or the hilar glands (OR = 0.85, p = 0.72). A trend toward increased severity of silicosis of the parenchyma was evident; however, this was not statistically significant (p = 0.08). Odds ratios for lung cancer and silicosis were higher at lower levels of cumulative silica dust exposure (ORs = 2.43, 1.72, 1.35 and 0.62 for lung cancer and autopsy silicosis of the parenchyma for the lowest, second, third, and highest quartiles of dust exposure, respectively; all p greater than 0.05). Cases did not differ from controls for total silica dust exposure, length of exposure, weighted average intensity of exposure, or number of shifts at high dust (all p greater than 0.20). The data do not support the hypothesis of a carcinogenic role for silica dust and no statistically sigificant associations were found between lung cancer and silicosis.
Bazelet, Corinna S.; Thompson, Aileen C.; Naskrecki, Piotr
The use of endemism and vascular plants only for biodiversity hotspot delineation has long been contested. Few studies have focused on the efficacy of global biodiversity hotspots for the conservation of insects, an important, abundant, and often ignored component of biodiversity. We aimed to test five alternative diversity measures for hotspot delineation and examine the efficacy of biodiversity hotspots for conserving a non-typical target organism, South African katydids. Using a 1° fishnet grid, we delineated katydid hotspots in two ways: (1) count-based: grid cells in the top 10% of total, endemic, threatened and/or sensitive species richness; vs. (2) score-based: grid cells with a mean value in the top 10% on a scoring system which scored each species on the basis of its IUCN Red List threat status, distribution, mobility and trophic level. We then compared katydid hotspots with each other and with recognized biodiversity hotspots. Grid cells within biodiversity hotspots had significantly higher count-based and score-based diversity than non-hotspot grid cells. There was a significant association between the three types of hotspots. Of the count-based measures, endemic species richness was the best surrogate for the others. However, the score-based measure out-performed all count-based diversity measures. Species richness was the least successful surrogate of all. The strong performance of the score-based method for hotspot prediction emphasizes the importance of including species’ natural history information for conservation decision-making, and is easily adaptable to other organisms. Furthermore, these results add empirical support for the efficacy of biodiversity hotspots in conserving non-target organisms. PMID:27631131
Yaya, G; Kobangué, L; Kémata, B; Gallé, D; Grésenguet, G
The authors return the results of a transverse prospective survey whose goal was to value the impact of struggle against the onchocerciasis after 20 years of distribution of ivermectin in a village of the Central African Republic. A transverse prospective survey with a descriptive and analytic aim of a sample of 393 topics aged of more than 5 years residing in Gami Village since more of 2 years and having benefitted the ivermectine in the last distribution that took place 10 months before. The epidemiological, clinical and parasitologic data introverted have been compared to the results of the previous investigations in the village. The parameters improved distinctly during the 20 years (1990-2010) notably the microfilarian indication (88% in 1990 against 19% in 2010), the middle microfilarian density (54 against 0,7), the CMFL Indication (39 against 0,67), the Knuttgen indication moved of the trance of age of 5-9 years to the one of more than 45 years since 1998), the cystic indication (36% against 8%), the ocular lesions (31% against 4%) of which onchocercian (28% against 2%), serious ocular lesions (16% against 1,3%), rate of blindness (9% against 0,8%), rate of meadow-blindness (9% against 0,8), important loss of vision (3% against 0,0%), ocular lesions in children of 6-10 years old (6% against 0,3%). These data permit to speak of control but not of elimination of the onchocerciasis in the grouping villager of Gami because of the persistence of the microfilarian indications susceptible to maintain the transmission of where necessity to pursue the struggle.
Kingsberry, Francemise St. Pierre
An underrepresentation of African American women in the superintendency exists in K-12 public schools. There is also a lack of research on their leadership and experiences in education. Although the number of women superintendents has increased over the years, the superintendency remains a male-dominated field and African American women remain in…
Farmer, Errick D.; Hope, Warren C.
African American males face major challenges in retention and graduation from institutions of higher education. The 6-year graduation rate for African American males at 4-year public institutions and private nonprofit colleges is less than 40%. This figure suggests that persistence toward degree attainment is a problem. The purpose of this study…
African Pentecostal churches are becoming increasingly important in Britain where they are growing at a time when mainstream Christianity is in decline. Originally functioning as social and religious support networks for African migrants, their growth has been stimulated by a conscious missionary agenda. Recently, there has been a shift towards a…
Balekouzou, Augustin; Yin, Ping; Afewerky, Henok Kessete; Bekolo, Cavin; Pamatika, Christian Maucler; Nambei, Sylvain Wilfrid; Djeintote, Marceline; Doui Doumgba, Antoine; Mossoro-Kpinde, Christian Diamont; Shu, Chang; Yin, Minghui; Fu, Zhen; Qing, Tingting; Yan, Mingming; Zhang, Jianyuan; Chen, Shaojun; Li, Hongyu; Xu, Zhongyu; Koffi, Boniface
Breast cancer is recognized as a major public health problem in developing countries; however, there is very little evidence of behavioral factors associated with breast cancer risk. This study was conducted to identify lifestyles as risk factors for breast cancer among Central African women. A case-control study was conducted with 174 cases confirmed histologically by the pathology unit of the National Laboratory and 348 age-matched controls. Data collection tools included a questionnaire with interviews and medical records of patients. Data were analyzed using SPSS software version 20. Odd ratio (OR) and 95% confidence intervals (95% CI) were obtained by unconditional logistic regression. In total, 522 women were studied with a mean age of 45.8 (SD = 13.4) years. By unconditional logistic regression model, women with breast cancer were more likely to have attained illiterate and elementary education level [11.23 (95% CI, 4.65-27.14) and 2.40 (95% CI, 1.15-4.99)], married [2.09 (95% CI, 1.18-3.71)], positive family history [2.31 (95% CI, 1.36-3.91)], radiation exposure [8.21 (95% CI, 5.04-13.38)], consumption charcuterie [10.82 (95% CI, 2.39-48.90)], fresh fish consumption [4.26 (95% CI, 1.56-11.65)], groundnut consumption [6.46 (95% CI, 2.57-16.27)], soybean consumption [16.74 (95% CI, 8.03-39.84)], alcohol [2.53 (95% CI, 1.39-4.60)], habit of keeping money in bras[3.57 (95% CI, 2.24-5.69)], overweight [5.36 (95% CI, 4.46-24.57)] and obesity [3.11(95% CI, 2.39-20.42)]. However, decreased risk of breast cancer was associated with being employed [0.32 (95% CI, 0.19-0.56)], urban residence [0.16 (95% CI, 0.07-0.37)], groundnut oil consumption [0.05 (95% CI, 0.02-0.14)], wine consumption [0.16 (95% CI, 0.09-0.26)], non habit of keeping cell phone in bras [0.56 (95% CI, 0.35-0.89)] and physical activity [0.71(95% CI, 0.14-0.84)]. The study showed that little or no education, marriage, positive family history of cancer, radiation exposure, charcuterie, fresh fish
Kaloga, Mamadou; Dioussé, Pauline; Diatta, Boubacar Ahy; Bammo, Mariama; Kourouma, Sarah; Diabate, Almamy; Gueye, Ndiaga; Dione, Haby; Diallo, Moussa; Diop, Bernard Marcel
Introduction Xeroderma pigmentosum is a rare autosomal recessive genetic disease. This disease predisposes patients to early-onset skin cancers, particularly squamous cell carcinoma. Here, we report 3 pediatric cases, including 2 deaths. Observation The subjects included 2 boys and 1 girl with skin type VI. All subjects were from consanguineous marriages, and the average age was 7.6 years. The patients all had ulcerative budding tumor lesions in the cephalic region, and the mean disease duration was 18 months. In all 3 cases, the diagnosis of xeroderma pigmentosum was made before the poikilodermal appearance of sun-exposed areas and photophobia. Neurological-type mental retardation was noted in 1 case. Histology confirmed squamous cell carcinoma in all 3 cases. The evolutions were marked by the death of 2 children (cases 1 and 3). In one case, the outcome was favorable following cancer excision and subsequent chemotherapy with adjuvant radiotherapy. Conclusion Squamous cell carcinoma is a serious complication related to xeroderma pigmentosum in Sub-Saharan Africa. Prevention is based on the early diagnosis of xeroderma pigmentosum, black skin photoprotection, screening and early treatment of lesions, and genetic counseling. PMID:27920683
Gechere, Geja; Terefe, Getachew; Belihu, Kelay
The effect of tsetse/trypanosomiasis control on cattle herd composition and growth and mortality of calves in tsetse controlled (by Southern Tsetse Eradication Project (STEP)) and uncontrolled blocks in southern Ethiopia was assessed. Structured questionnaire was used to interview 182 households to estimate cattle herd composition and calf mortality. Calves were bled to examine the presence of trypanosomes by the buffy coat technique. Forty NGU traps were deployed and fly catches determined. A case-control study was performed on 40 calves for 6 months to estimate calve growth parameters. Accordingly, the mean cattle herd size was lower in tsetse-controlled block than in the uncontrolled block, whereas the relative number of calves in a herd tend to be higher in the tsetse-controlled block (P = 0.06). While there was no report of cattle mortality in tsetse-controlled block, 16.48 % of the respondents have lost calves in tsetse-uncontrolled block in 1 year time. The prevalence of trypanosome positive calves was 2.95 % for uncontrolled block but no positive case in tsetse-controlled block. The apparent densities of flies/trap/day in tsetse-uncontrolled block were 30-fold higher than in tsetse-controlled block (P < 0.01). The case-control study revealed that the mean body weight gain of calves in tsetse-controlled block (40.23 ± 0.7 kg) was significantly higher than that of the uncontrolled block (34.74 ± 0.68 kg). The above findings strongly suggest that the intervention by the STEP project has significantly reduced tsetse population and trypanosomiasis consequently contributing to improved calf growth and survival.
Park, Jie Y.
Although immigrant youth make up more than 20 percent of school-age children in the U.S., little is known about how they manage school assignments and texts. In this paper the author presents Tara (pseudonym) as a telling case of a first-generation immigrant youth who is encountering and grappling with academic literacy--defined as not only the…
Mabokela, Reitumetse Obakeng, Ed.; King, Kimberly Lenease, Ed.
The case studies in this collection show the changes in higher education in South Africa that are taking place in response to the revolutionary political changes that have come with the end of apartheid. The chapters are: (1) "Transformation through Negotiation: The University of Port Elizabeth's Experiences, Challenges, and Progress"…
Louw, Ina; Zuber-Skeritt, Ortrun
Leadership development in higher education is of vital importance to South Africa's future. We present a case study that focuses on a leadership development programme (LDP) through action learning and action research (ALAR) for women academics in South Africa during 2000 and 2001. It identifies the effects of the LDP on participants five years…
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare condition that occurs normally in the anterior maxilla of infants aged <1 year. The use of clinical and imaging tools for MNTI is extremely important to prevent problems with function as well as the aesthetic features in a breastfeeding child. Brazil is a multiethnic country with a poor epidemiological policy and little data to track the incidence of certain diseases, including MNTI. It is important to study this pathology with ethnicity as a factor to improve the current epidemiological programs and establish better post-treatment management. This paper describes a case of a 2-month-old male of African-indigenous descent and Brazilian Amazon residency, who presented to our unit in 2009 with a history of an expanding mass involving the anterior maxilla. Clinical and computerized tomography scans were used to diagnose the mass as MNTI, which was removed by total excision. A biopsy later confirmed the MNTI diagnosis. PMID:24274360
Black, Robert; Fava, Fabio; Mattei, Niccolo; Robert, Vincent; Seal, Susan; Verdier, Valerie
production and the economy of this depressed areas. However, the problems bound to environmental protection must not be forgotten; priority should be given to monitor the risks of introduction of foreign species. Red biotechnologies potentially bring a vast domain of powerful tools and processes to achieve better human health, most notably improved diagnostics by molecular techniques, better targeting of pathogens and a better knowledge of their sensitivities to drugs to permit better treatment. Biosafety regulatory frameworks had been initiated in several countries, starting with primary biosafety law. However, disparate attitudes to the purpose of biosafety regulation (e.g., fostering informed decision-making versus 'giving the green-light for a flood of GMOs') currently prevent a needed consensus for sub-regional harmonisation. To date, most R&D funding has come from North America with some commercial interests from Asia, but African biotechnology workers expressed strong desire for (re-)engagement with interested parties from the European Union. Although in some of the visited countries there are very well qualified personnel in molecular biology and biosafety/regulation, the main message received is that human resources and capacity building in-house are still needed. This could be achieved through home-based courses and capacity-building including funds for post-degree research to motivate and retain trained staff.
Romaña, Cristina; Emperaire, Laure; Jansen, Ana Maria
Modifications of the landscape by human activity and migratory movements contribute to the emergence or reemergence of zoonotic and human diseases, particularly those transmitted by insects which often escape the changing environmental conditions, adapting and modifying their trophic networks and morphology, including their genotype. A better understanding of relationships between ecological factors, human factors, and anthropozoonoses is vital to be able to identify variables that allow one to map the risk for human populations. This is the main objective of the research program Landscape Ecology, Land-Use Dynamics, and Eco-Pathogenic Complexes: Eco-Epidemiologic Risk in the Case of American Trypanosomiasis, developed in various Brazilian ecosystems. The authors describe the program's conceptual and methodological basis and highlight the role of eco-epidemiology for studying the structure and function of natural and anthropogenic foci of infection. Modeling spatial and temporal dynamics can help predict and monitor such tropical diseases.
Bodley, A L; McGarry, M W; Shapiro, T A
The trypanosomes and Leishmania species are parasitic protozoa that afflict millions of people throughout the world. If not treated, African trypanosomiasis and visceral leishmaniasis are fatal. The available drugs are severely limited by toxicity, marginal efficacy, the requirement for parenteral administration, and spreading drug resistance. In this study, a spectrophotometric assay was developed and validated for measuring the cytotoxicity of test compounds against axenically cultured bloodstream-form Trypanosoma brucei (African trypanosomes) and promastigotes of Leishmania donovani. Enzymatic hydrolysis of p-nitrophenyl phosphate, monitored by a microtiter plate reader, is a reliable surrogate for parasite cell counts. The assay is simple, inexpensive, and highly reproducible. The coefficient of variation for EC50 values is < 10% for determinations obtained over several months. This method permits the rapid screening of candidates for much-needed new drugs against these parasites.
Myburgh, Elmarie; Coles, Jonathan A; Ritchie, Ryan; Kennedy, Peter G E; McLatchie, Alex P; Rodgers, Jean; Taylor, Martin C; Barrett, Michael P; Brewer, James M; Mottram, Jeremy C
HUMAN AFRICAN TRYPANOSOMIASIS (HAT) MANIFESTS IN TWO STAGES OF DISEASE: firstly, haemolymphatic, and secondly, an encephalitic phase involving the central nervous system (CNS). New drugs to treat the second-stage disease are urgently needed, yet testing of novel drug candidates is a slow process because the established animal model relies on detecting parasitemia in the blood as late as 180 days after treatment. To expedite compound screening, we have modified the GVR35 strain of Trypanosoma brucei brucei to express luciferase, and have monitored parasite distribution in infected mice following treatment with trypanocidal compounds using serial, non-invasive, bioluminescence imaging. Parasites were detected in the brains of infected mice following treatment with diminazene, a drug which cures stage 1 but not stage 2 disease. Intravital multi-photon microscopy revealed that trypanosomes enter the brain meninges as early as day 5 post-infection but can be killed by diminazene, whereas those that cross the blood-brain barrier and enter the parenchyma by day 21 survived treatment and later caused bloodstream recrudescence. In contrast, all bioluminescent parasites were permanently eliminated by treatment with melarsoprol and DB829, compounds known to cure stage 2 disease. We show that this use of imaging reduces by two thirds the time taken to assess drug efficacy and provides a dual-modal imaging platform for monitoring trypanosome infection in different areas of the brain.
Israel, Nejla; Markova, Tsveti
Calciphylaxis is a lethal disorder seen in patients with end-stage renal disease and is characterized by painful necrotic skin lesions. The pathophysiology is still unknown. Elevated calcium, phosphorous and parathormone appear to play a role in causing small and medium sized vasculopathy. Diagnosis is delayed, prognosis is poor and mortality remains high. In this article we describe the case of calciphylaxis in a patient with chronic renal failure and multiple medical comorbidities, and discuss diagnostic management, prognosis and treatment options. PMID:19830094
Okafor, Victor Oguejiofor
Presents a case study of controversies related to African studies and makes the case for an Africological pedagogical approach to African Civilization. The title "African Civilization" reflects the African place in the whole of world civilization even though that place is itself a multiple entity. (SLD)
Kalthan, E; Dondo-Fongbia, J P; Yambele, S; Dieu-Creer, L R; Zepio, R; Pamatika, C M
An outbreak of monkeypox occurred in the district of Bangassou in 2015. The monkeypox is a re-emerging zoonosis of viral origin highly contagious. It is an eruptive fever which evolves in an epidemic manner. An investigation was held December 10, 2015, to February 10, 2016 in the focus of the epidemic. Its objective was to describe the epidemic according to the time, places and people and to determine the incidence and lethality of the disease. This was a descriptive study. The data collection was made by interview and using a linear plug composed of several sections. All suspected cases were taken into account. The interview was done with patients or the parents of sick children. The blood and the contents of the lesions were collected and sent to the laboratory of the Institut Pasteur in Bangui for confirmation. Our data were analyzed with Epi info7. In total 12 patients had been registered including 9 secondary cases. Patients aged 31 to 40 years and less than 10 years were most affected. In addition, adults were most affected by the disease (8/12). The average age was 25 years with extremes at 15 months and 41 years. The sex male/female ratio was 1. The overall attack rate of disease and lethality were 0.2 per 1000 inhabitants and 25% respectively. The fatality was 67% among children less than 10 years. Fever and rash were the main symptoms of the disease. Lymphadenopathy was present in 54.5%. Ten of the 12 patients were hospitalized (83%). The average duration of hospitalization was 13 days with the extremes 6 and 28 days. The monkeypox like smallpox remains a serious and fatal disease in children. A survey of animal reservoirs complained to identify strains of the virus is essential. During an outbreak, good communication and isolation of patients may break the chain of transmission. Other measures to limit their contact with the forest or virus reservoirs are to be encouraged.
Balekouzou, Augustin; Yin, Ping; Afewerky, Henok Kessete; Bekolo, Cavin; Pamatika, Christian Maucler; Nambei, Sylvain Wilfrid; Djeintote, Marceline; Doui Doumgba, Antoine; Mossoro-Kpinde, Christian Diamont; Shu, Chang; Yin, Minghui; Fu, Zhen; Qing, Tingting; Yan, Mingming; Zhang, Jianyuan; Chen, Shaojun; Li, Hongyu; Xu, Zhongyu; Koffi, Boniface
Breast cancer is recognized as a major public health problem in developing countries; however, there is very little evidence of behavioral factors associated with breast cancer risk. This study was conducted to identify lifestyles as risk factors for breast cancer among Central African women. A case-control study was conducted with 174 cases confirmed histologically by the pathology unit of the National Laboratory and 348 age-matched controls. Data collection tools included a questionnaire with interviews and medical records of patients. Data were analyzed using SPSS software version 20. Odd ratio (OR) and 95% confidence intervals (95% CI) were obtained by unconditional logistic regression. In total, 522 women were studied with a mean age of 45.8 (SD = 13.4) years. By unconditional logistic regression model, women with breast cancer were more likely to have attained illiterate and elementary education level [11.23 (95% CI, 4.65–27.14) and 2.40 (95% CI, 1.15–4.99)], married [2.09 (95% CI, 1.18–3.71)], positive family history [2.31 (95% CI, 1.36–3.91)], radiation exposure [8.21 (95% CI, 5.04–13.38)], consumption charcuterie [10.82 (95% CI, 2.39–48.90)], fresh fish consumption [4.26 (95% CI, 1.56–11.65)], groundnut consumption [6.46 (95% CI, 2.57–16.27)], soybean consumption [16.74 (95% CI, 8.03–39.84)], alcohol [2.53 (95% CI, 1.39–4.60)], habit of keeping money in bras[3.57 (95% CI, 2.24–5.69)], overweight [5.36 (95% CI, 4.46–24.57)] and obesity [3.11(95% CI, 2.39–20.42)]. However, decreased risk of breast cancer was associated with being employed [0.32 (95% CI, 0.19–0.56)], urban residence [0.16 (95% CI, 0.07–0.37)], groundnut oil consumption [0.05 (95% CI, 0.02–0.14)], wine consumption [0.16 (95% CI, 0.09–0.26)], non habit of keeping cell phone in bras [0.56 (95% CI, 0.35–0.89)] and physical activity [0.71(95% CI, 0.14–0.84)]. The study showed that little or no education, marriage, positive family history of cancer, radiation
Mechanic, Leah E; Millikan, Robert C; Player, Jon; de Cotret, Allan René; Winkel, Scott; Worley, Kendra; Heard, Kristin; Heard, Kimberley; Tse, Chiu-Kit; Keku, Temitope
Polymorphisms exist in several genes involved in nucleotide excision repair (NER), the principal pathway for removal of smoking-induced DNA damage. An epidemiologic study was conducted to determine whether these polymorphisms modify the association between smoking and breast cancer. DNA samples and exposure histories were analyzed as part of a large population-based case-control study of breast cancer in North Carolina. The study population included 2311 cases (894 African Americans, 1417 whites) and 2022 controls (788 African Americans, 1234 whites). Odds ratios (ORs) were calculated for breast cancer and smoking, and for breast cancer and nine non-synonymous coding polymorphisms in six NER genes (XPD codons 312 and 751, RAD23B codon 249, XPG codon 1104, XPC codon 939, XPF codons 415 and 662, and ERCC6 codons 1213 and 1230). Modification of ORs for smoking by single and combined NER genotypes was investigated. In this study population, smoking was more strongly associated with breast cancer in African American women compared with white women. Among African American women, the association of breast cancer and smoking was strongest among women with specific combinations of NER genotypes. Evidence for multiplicative interaction was found between combined NER genotypes and smoking dose (likelihood ratio test P = 0.06), duration (P = 0.09), time since cessation (P = 0.02), age at initiation (P = 0.04) and former smoking (P = 0.03). No interactions were observed in white women. Therefore, polymorphisms in NER genes may modify the relationship between breast cancer and smoking. These results are consistent with previous evidence of exposure-specific p53 mutations in breast tumors from current and former smokers, suggesting that smoking may play a role in breast cancer etiology.
Virgilio, Massimiliano; Jordaens, Kurt; Breman, Floris C.; Backeljau, Thierry; De Meyer, Marc
We propose a general working strategy to deal with incomplete reference libraries in the DNA barcoding identification of species. Considering that (1) queries with a large genetic distance with their best DNA barcode match are more likely to be misidentified and (2) imposing a distance threshold profitably reduces identification errors, we modelled relationships between identification performances and distance thresholds in four DNA barcode libraries of Diptera (n = 4270), Lepidoptera (n = 7577), Hymenoptera (n = 2067) and Tephritidae (n = 602 DNA barcodes). In all cases, more restrictive distance thresholds produced a gradual increase in the proportion of true negatives, a gradual decrease of false positives and more abrupt variations in the proportions of true positives and false negatives. More restrictive distance thresholds improved precision, yet negatively affected accuracy due to the higher proportions of queries discarded (viz. having a distance query-best match above the threshold). Using a simple linear regression we calculated an ad hoc distance threshold for the tephritid library producing an estimated relative identification error <0.05. According to the expectations, when we used this threshold for the identification of 188 independently collected tephritids, less than 5% of queries with a distance query-best match below the threshold were misidentified. Ad hoc thresholds can be calculated for each particular reference library of DNA barcodes and should be used as cut-off mark defining whether we can proceed identifying the query with a known estimated error probability (e.g. 5%) or whether we should discard the query and consider alternative/complementary identification methods. PMID:22359600
Virgilio, Massimiliano; Jordaens, Kurt; Breman, Floris C; Backeljau, Thierry; De Meyer, Marc
We propose a general working strategy to deal with incomplete reference libraries in the DNA barcoding identification of species. Considering that (1) queries with a large genetic distance with their best DNA barcode match are more likely to be misidentified and (2) imposing a distance threshold profitably reduces identification errors, we modelled relationships between identification performances and distance thresholds in four DNA barcode libraries of Diptera (n = 4270), Lepidoptera (n = 7577), Hymenoptera (n = 2067) and Tephritidae (n = 602 DNA barcodes). In all cases, more restrictive distance thresholds produced a gradual increase in the proportion of true negatives, a gradual decrease of false positives and more abrupt variations in the proportions of true positives and false negatives. More restrictive distance thresholds improved precision, yet negatively affected accuracy due to the higher proportions of queries discarded (viz. having a distance query-best match above the threshold). Using a simple linear regression we calculated an ad hoc distance threshold for the tephritid library producing an estimated relative identification error <0.05. According to the expectations, when we used this threshold for the identification of 188 independently collected tephritids, less than 5% of queries with a distance query-best match below the threshold were misidentified. Ad hoc thresholds can be calculated for each particular reference library of DNA barcodes and should be used as cut-off mark defining whether we can proceed identifying the query with a known estimated error probability (e.g. 5%) or whether we should discard the query and consider alternative/complementary identification methods.
Vanthomme, Hadrien P A; Tobi, Elie; Todd, Angelique F; Korte, Lisa; Alonso, Alfonso
Unsustainable hunting outside protected areas is threatening tropical biodiversity worldwide and requires conservationists to engage increasingly in antipoaching activities. Following the example of ecocertified logging companies, we argue that other extractive industries managing large concessions should engage in antipoaching activities as part of their environmental management plans. Onshore hydrocarbon concessions should also adopt antipoaching protocols as a standard because they represent a biodiversity threat comparable to logging. We examined the spatiotemporal patterns of small- and large-mammal poaching in an onshore oil concession in Gabon, Central Africa, with a Bayesian occupancy model based on signs of poaching collected from 2010 to 2015 on antipoaching patrols. Patrol locations were initially determined based on local intelligence and past patrol successes (adaptive management) and subsequently with a systematic sampling of the concession. We generated maps of poaching probability in the concession and determined the temporal trends of this threat over 5 years. The spatiotemporal patterns of large- and small-mammal poaching differed throughout the concession, and likely these groups will need different management strategies. By elucidating the relationship between site-specific sampling effort and detection probability, the Bayesian method allowed us to set goals for future antipoaching patrols. Our results indicate that a combination of systematic sampling and adaptive management data is necessary to infer spatiotemporal patterns with the statistical method we used. On the basis of our case study, we recommend hydrocarbon companies interested in implementing efficient antipoaching activities in their onshore concessions to lay the foundation of long-needed industry standards by: adequately measuring antipoaching effort; mixing adaptive management and balanced sampling; setting goals for antipoaching effort; pairing patrols with large
Lewis, Bradford F.
In the United States, African Americans are underrepresented among employed Ph.D. holding scientists; they comprise less than 2% of the scientific population and 12% of the United States population. Educational theorists, focusing on the career choices of African Americans as the cause of underrepresentation, have identified many factors that are associated with the underrepresentation of African Americans in science. Some of these factors are: lack of interest in science, poor academic preparation, high interest in social-oriented careers, poor educational and career planning, unfavorable images of scientists, impoverished family backgrounds, and lack of confidence in ability. This plethora of factors indicates that there is yet equivocation in literature as to the cause of underrepresentation. The objective of this study is to deepen current understanding, by providing explanations for the career decisions of African American students. Adopting a theoretical framework which maintains that human behavior is directed by world view and that world view is shaped by environment, the present study seeks to analyze the world view contents of three African American college students: two science majors and one non-science major. The aim of this study is to analyze the world view contents of the students to identify the salient world view images and assumptions that influence their career decisions. The research employs interpretive methodology and a case study design. Primary methods of data collection are interview and interview analysis. The dissertation reports the results of interviews, which include explanations for each respondent's career decisions; and the influence of three factors (expectation of monetary gain, the impact of role models, and respondents' level of self-confidence in ability) on the respondents' career decisions. Findings indicate that the science major has a greater capacity, than the non-science majors, to accommodate world view images and
Rudramurthy, G R; Sengupta, P P; Balamurugan, V; Prabhudas, K; Rahman, H
The invariant surface glycoprotein (ISG-75) gene of Trypanosoma evansi buffalo isolate from Karnataka state in India was sequenced and analyzed to elucidate its relationship with other isolates/species. The sequenced ISG-75 gene was also explored to device a polymerase chain reaction (PCR) strategy for the diagnosis of trypanosomiasis in carrier animals. The six cloned ISG gene sequences revealed the open reading frame (ORF) of 1572 and 1527 nucleotide (nt) encoding a polypeptide of 523 and 508 amino acids (aa) respectively and belongs ISG-75 gene family. Sequence analysis revealed 91-100% and 65-99% similarity at nt and aa levels, respectively with other isolates/species and belongs to the RoTat 1.2 strain. The diagnostic PCR based on ISG-75 sequence amplifies a 407 bp product specifically from the different T. evansi isolates and could detect 0.04 pg and 1.2 ng of DNA from purified trypanosomes and T. evansi infected rat blood samples respectively. Subsequently the PCR detected 0.02 and 0.27 trypanosomes ml(-1) respectively, from purified trypanosomes and T. evansi (buffalo isolate) infected rat blood. By the developed PCR assay trypanosomal nucleic acid was detected in experimental rats and buffalo on 24 h post infection (p.i.) and 3rd day post infection (d.p.i.), respectively. The developed ISG-75 gene based PCR assay could be useful in detection of carrier status of trypanosomiasis in animals.
Ranjithkumar, Muthusamy; Saravanan, Buddhi Chandrasekaran; Yadav, Suresh Chandra; Kumar, Rajender; Singh, Rajendra; Dey, Sahadeb
Trypanosoma evansi infection typically produces wasting disease, but it can also develop into a neurological or meningoencephalitis form in equids. Trypanosomiasis in horses was treated with quinapyramine sulfate, and all the 14 infected animals were recovered clinically. After clinical recovery, four animals developed a neurological form of the disease at various intervals. Two of these animals treated with diminazene aceturate recovered temporarily. Repeated attempts failed to find the parasite in the blood or the cerebrospinal fluid (CSF), but all of the animals were positive in enzyme-linked immunosorbent assay. The calculation of the antibody index (AI) in the serum and the CSF and polymerase chain reaction (PCR) analysis of the CSF and brain tissue were carried out to confirm the neuro-infection. We found PCR and AI analyses of the CSF to be useful tools in the diagnosis of the neurological form of trypanosomiasis when the organism cannot be found in the blood or CSF. The increased albumin quotient is indicative of barrier leakage due to neuroinflammation. The biochemical changes in the CSF due to nervous system trypanosomiasis include increases in the albumin quotient, total protein, and urea nitrogen. It seems to be the first report on relapse of the nervous form of trypanosomiasis in equids even after quinapyramine treatment in endemic areas.
Koutangni, Thibaut; Boubacar Maïnassara, Halima; Mueller, Judith E.
Background To facilitate the interpretation of meningococcal meningitis epidemiology in the “African meningitis belt”, we aimed at obtaining serogroup-specific pooled estimates of incidence, carriage and case-carrier ratios for meningococcal meningitis in the African meningitis belt and describe their variations across the endemic, hyperendemic and epidemic context. Methods We conducted a systematic review and meta-analysis of studies reporting serogroup-specific meningococcal meningitis monthly incidence and carriage in the same population and time period. Epidemiological contexts were defined as endemic (wet season, no epidemic), hyperendemic (dry season, no epidemic), and epidemic (dry season, epidemic). Findings Eight studies reporting a total of eighty pairs of serogroup-specific meningococcal meningitis incidence and carriage estimates were included in this review. For serogroup A, changes associated with the transition from endemic to hyperendemic incidence and from hyperendemic to epidemic incidence were 15-fold and 120-fold respectively. Changes in carriage prevalence associated with both transitions were 1-fold and 30-fold respectively. For serogroup W and X, the transition from endemic to hyperendemic incidence involved a 4-fold and 1•1-fold increase respectively. Increases in carriage prevalence for the later transition were 7-fold and 1•7-fold respectively. No data were available for the hyperendemic-epidemic transition for these serogroups. Our findings suggested that the regular seasonal variation in serogroup A meningococcal meningitis incidence between the rainy and the dry season could be mainly driven by seasonal change in the ratio of clinical cases to subclinical infections. In contrast appearance of epidemic incidences is related to a substantial increase in transmission and colonisation and to lesser extent with changes in the case-carrier ratio. Conclusion Seasonal change in the rate of progression to disease given carriage
Strike and protest activity at South African universities continues to be prevalent nearly two decades after the dismantling of apartheid, although there has been a shift away from directing strikes and protests against the government (during the apartheid era), to directing them against higher education institutions and management (since the…
Swart, Arthur James; Lombard, Kobus; de Jager, Henk
Poor academic success by African engineering students is currently experienced in many higher educational institutions, contributing to lower financial subsidies by local governments. One of the contributing factors to this low academic success may be the poor time management skills of these students. This article endeavours to explore this…
Keller, Heidi; Voelker, Susanne; Yovsi, Relindis Dzeaye
The present study compares conceptions about parenting in two cultural communities that may be expected to hold different views on parent-child relationships. Sociodemographically diverse samples of 46 Northern German and 39 West African Nso women evaluated parenting behavior observed in 10 Nso and 10 German videotaped mother-infant interaction…
This dissertation analyzed and described transitions from a theological or Bible college to a Christian liberal arts college or university in East African context. The research was specially driven by the desire to find out the reasons for such transitions, the challenges of the transition process and how such transitions affect the mission of the…
Portnoi, Laura M.
South African higher education has been experiencing profound and vigorous transformations in the post-apartheid era. At the same time, global trends toward competition and employment equity contribute to the complexities of the country's higher education environment. These global and local developments combine to impact the working environment of…
My interest in critical leaderful educational practices emanated from my experiences as a researcher in a South African National Department of Education project that piloted the White Paper on "Inclusive Education Policy from 2001-2003" and in 2006 when I worked as a volunteer consultant with Twenty30, an independent, not for profit…
Mavunga, George; Cachalia, Fahmida
This study compared how the cohort of extended diploma students enrolled at a comprehensive South African university in 2012 perceived the programmes for which they were enrolled at the beginning of their first year and towards the end of the year. Data were gathered using questionnaires and semi-structured interviews involving students enrolled…
Le Roux, R. G.; And Others
Up to 10 persons a year are awarded medals for high performance in the South African Mathematics Olympiad, designed to stimulate the love for mathematics and to discover and reward youthful talent and aptitude. Questionnaires were sent to this group to ascertain their achievements, as a means of evaluating the effectiveness of the Olympiad. In the…
Odetunde, Florence Olayinka
This study explored how social integration of African immigrants in the Louisville metropolitan area of Kentucky could be a factor in the academic achievements of their children. It involved critically investigating how the process of their adjustments as immigrants might have been shaped by various personal and environmental factors such as…
Macdonald, Ian S.; Bullen, Mark; Kozak, R. A.
This study investigated appropriate pedagogical techniques for workplace e-learning programs in the South African wood products (furniture) manufacturing sector. The study found that learners responded favourably to constructivist teaching approaches, such as asynchronous discussions, open-ended task-based activities, and assignments incorporating…
Peele-Eady, Tryphenia B.
In this article, the author explores how African American children in a Black church Sunday school community in northern California developed positive membership identity. Focal participants were Sunday school children ages 9 to 12 and their Sunday school teachers. Drawn from a two-year ethnographic study, data showed that adults prepared children…
Ward, Cherie A.
This study examined the use of poetry as a multimodal communicative text to encourage reading engagement in selected African-American learners with mild intellectual disabilities. Framed by critical discourse theory, genre theory, and Gardner's theory of multiple intelligences, this investigation presented poetry as an alternative text…
Pannell, Lynette Martin
The purpose of this study was to investigate the differences of Measures of Academic Progress (MAP) scores between fourth-grade African American male students who were enrolled in single-sex classrooms and their counterparts who were enrolled in coeducational classrooms. The research provided descriptive data concerning one Title I school in rural…
This study examines whether participating in competitive policy debate influences high school completion, academic achievement, and college readiness for African American male students. The analysis examines data from the Chicago Debate League from 1997 to 2006. Debate participants were 70% more likely to graduate and three times less likely to…
Fort Detrick, MD 21702-5012. AUTHORITY USAMRMC, 5 Mar 2002 THIS PAGE IS UNCLASSIFIED AD Award Number: DAMD17-97- 1 -7287 TITLE: Methyl-Deficient Diets and...RELATE TO THEM. LIMITED RIGHTS LEGEND 7 / Award Number: DAMD17-97- 1 -7287 Organization: Meharry Medical College Location of Limited Rights Data (Pages...Risks of Breast CanCer Among~ rAMD17-97- 1 -7287 African-American Women: A Case-Control Study by Methylation Status of thet ER Gone 6. AUTHOR(S) i
Korczak, J.F.; Goldstein, A.M.; Kase, R.G.
We present an 8-year-old African-American boy with medulloblastoma and nevoid basal cell carcinoma syndrome (NBCCS) who exhibited the radiosensitive response of basal cell carcinoma (BCC) formation in the area irradiated for medulloblastoma. Such a response is well-documented in Caucasian NBCCS patients with medulloblastoma. The propositus was diagnosed with medulloblastoma at the age of 2 years and underwent surgery, chemotherapy, and craniospinal irradiation. At the age of 6 years, he was diagnosed with NBCCS following his presentation with a large odontogenic keratocyst of the mandible, pits of the palms and soles and numerous BCCs in the area of the back and neck that had been irradiated previously for medulloblastoma. Examination of other relatives showed that the propositus mother also had NBCCS but was more mildly affected; in particular, she had no BCCs. This case illustrates complex gene-environment interaction, in that increased skin pigmentation in African-Americans is presumably protective against ultraviolet, but not ionizing, radiation. This case and other similar cases in the literature show the importance of considering NBCCS in the differential diagnosis of any patient who presents with a medulloblastoma, especially before the age of 5 years, and of examining other close relatives for signs of NBCCS to determine the patient`s at-risk status. Finally, for individuals who are radiosensitive, protocols that utilize chemotherapy in lieu of radiotherapy should be considered. 27 refs., 4 figs.
Wachira, Eunice; Tran, Kayla; Taylor, Sara; Hoger, Sally; Dunn, James
Most cases of osteomyelitis in children are caused by Staphylococcus aureus, although Kingella kingae, various streptococci, and Salmonella species also underlie this condition. Organisms such as Mycobacterium, Histoplasma, and Cryptococcus are much less commonly identified as etiologic agents in osteomyelitis. This case report describes a 16-month-old boy of Hispanic/African American ethnicity who had extensive inflammation of and discharge from his right ankle. Imaging studies supported a diagnosis of osteomyelitis. Acid-fast bacillus (AFB) and routine wound cultures were ordered on the wound discharge. The AFB culture yielded a positive result for Mycobacterium bovis, and molecular diagnostic testing further genotyped the microorganism as Mycobacterium bovis, Bacillus Calmette-Guerin (BCG). Herein, we report a rare case of osteomyelitis that we believe resulted from a BCG vaccine that the patient had received outside the United States.
Naidoo, S; Chikte, U M
Cancrum oris (noma) is a gangrenous infection that develops in the mouth and spreads rapidly to other parts of the face. The disease occurs mostly in conditions of poverty, poor hygiene and malnutrition. In sub-Saharan Africa the frequency in several countries is estimated to be 1-7 cases per 1,000 population, and as many as 12 cases per 1,000 in the most affected communities. About 90% of these children die without receiving any care, yet the disease can, and should, be prevented. With increasing numbers of children who are malnourished and who have compromised immune systems (compounded by the HIV pandemic) the prevalence of conditions such as noma is likely to increase. Among the earliest features of noma are excessive salivation, marked fetor oris, facial oedema and a greyish-black discolouration of the skin in the affected area. This devastating gangrenous lesion may involve the cheek, the chin, the infra-orbital margin, palate, nose, antrum and virtually any part of the face. This report describes a 4-year-old HIV-positive African girl, who was abandoned, discharged from the Plastics Unit and now lives in a child care sanctuary. Little is known about her history prior to her arrival at the home a few weeks previously. The clinical examination revealed a delay in growth and physical development equivalent to that of a 2-year-old child. The left cheek had a perforating ulcer in a healing phase. The perforation, about 1 cm in diameter, was surrounded by oedematous tissues showing a mild to moderate erythema. The peripheral oedema extended to the lower palpebral, the upper labial, left labial commissural, mandibular and pre-parotid regions. Submental, submandibular and cervical lymph nodes were mildly painful upon palpation. The child was not pyretic. The intra-oral examination revealed the features of acute necrotising gingivitis (ANG). ANG was generalised and showed classic interdental crater-like ulcers covered with whitish debris. Halitosis was pronounced
Shen, Bo-Wen; Tao, Wei-Kuo; Wu, Man-Li C.
In this study, extended -range (30 -day) high-resolution simulations with the NASA global mesoscale model are conducted to simulate the initiation and propagation of six consecutive African easterly waves (AEWs) from late August to September 2006 and their association with hurricane formation. It is shown that the statistical characteristics of individual AEWs are realistically simulated with larger errors in the 5th and 6th AEWs. Remarkable simulations of a mean African easterly jet (AEJ) are also obtained. Nine additional 30 -day experiments suggest that although land surface processes might contribute to the predictability of the AEJ and AEWs, the initiation and detailed evolution of AEWs still depend on the accurate representation of dynamic and land surface initial conditions and their time -varying nonlinear interactions. Of interest is the potential to extend the lead time for predicting hurricane formation (e.g., a lead time of up to 22 days) as the 4th AEW is realistically simulated.
International and African discourses on the HIV/AIDS pandemic and intervention neglect the role of religion and religious organizations. Social science perspectives in tackling health and disease neglect religious doctrines and faith central to worldviews and praxis of religious groups. Both aspects are important for religious groups and individuals affected by HIV/AIDS. Informed by a religious studies paradigm and through the religious ethnography of the Redeemed Christian Church of God (RCCG) in Nigeria and the Diaspora, this article demonstrates mechanisms employed by African Pentecostals to combat the epidemic and provide support for infected members. The RCCG conceptualization of disease and healing is central to understanding responses and measures in combating HIV/AIDS.
Under the direction of Sharon Murphy Augustine, Ph.D./Ph.D Curriculum and Instruction There was a substantial performance gap among African Americans and other ethnic groups. Additionally, African American students in a Title I school were at a significantly high risk of not meeting or exceeding on performance tests in science. Past reports have shown average gains in some subject areas, and declines in others (NCES, 2011; GADOE, 2012). Current instructional strategies and the lack of literacy within the biology classroom created a problem for African American high school students on national and state assessments. The purpose of this study was to examine the perceptions of African American students and teachers in the context of literacy and biology through the incorporation of an interactive notebook and other literacy strategies. The data was collected three ways: field notes for a two week observation period within the biology classroom, student and teacher interviews, and student work samples. During the observations, student work collection, and interviews, I looked for the following codes: active learning, constructive learning, collaborative learning, authentic learning, and intentional learning. In the process of coding for the pre-determined codes, three more codes emerged. The three codes that emerged were organization, studying/student ownership, and student teacher relationships. Students and teachers both solidified the notion that literacy and biology worked well together. The implemented literacy strategies were something that both teachers and students appreciated in their learning of biology. Overall students and teachers perceived that the interactive notebook along Cornell notes, Thinking maps, close reads, writing, lab experiments, and group work created meaningful learning experiences within the biology classroom.
Muhammad, Rhonda K.
This qualitative study examined the instructional practices of an experienced African American mathematics teacher to determine his perceived capabilities in augmenting academic proficiency for his African American male students. Provided in this descriptive case study are the lived experiences of an African American male teacher working to move…
Rosypal, Alexa C; Tripp, Shanesha; Kinlaw, Christopher; Sharma, R N; Stone, D; Dubey, J P
Canine leishmaniasis and American trypanosomiasis (AT) are caused by related hemoflagellated parasites, Leishmania spp. and Trypanosoma cruzi, which share several common host species. Dogs are reservoirs for human infections by both pathogens. We determined the prevalence of antibodies to Leishmania spp. and T. cruzi in dogs from Grenada, West Indies. We examined 70 dog sera using the qualitative immunochromatographic dipstick tests (ICTs) based on recombinant antigens specific for visceral leishmaniasis and AT. Antibodies to visceral Leishmania were not detected in Grenadian dogs by ICT. Using the canine dipsticks for AT, antibodies to T. cruzi were determined in 3 (4.3%) of the 70 dogs. Results from this study indicate that dogs in Grenada are exposed in low levels to T. cruzi , but not to visceral Leishmania spp. at all.
Navarro, Maribel; Gabbiani, Chiara; Messori, Luigi; Gambino, Dinorah
Tropical diseases today constitute a major health problem and a big challenge for drug discovery. Because of the limited arsenal of effective antiparasitic agents and the frequent appearance of chemoresistance, there is an urgent and continuous need to develop new drugs against these ailments. Metal compounds still offer excellent opportunities to find new 'leads' against the major protozoan diseases such as malaria, leishmaniasis and trypanosomiasis. A few metal-based drugs are already available in this therapeutic area, and others are currently being developed. Recent progress in parasite genomics and the identification of a few biomolecular targets hold great promise for the discovery of new 'mechanism-based' antiparasitic metallodrugs. The trends and perspectives for this exciting research field are outlined here.
Miller, Bill R; Roitberg, Adrian E
Chagas disease (or American trypanosomiasis) is a deadly tropical disease that affects millions of people worldwide, primarily in rural regions of South America. Trypanosoma cruzi, the parasitic cause of Chagas disease, possesses a membrane-anchored trans-sialidase enzyme that transfers sialic acids from the host cell surface to the parasitic cell surface, allowing T. cruzi to effectively evade the host's immune system. This enzyme has no analogous human counterpart and thus has become an interesting drug target to combat the parasite. Recent computational efforts have improved our knowledge about the enzyme's structure, dynamics and catalyzed reaction. Many compounds have been tested against trans-sialidase activity, but no strong inhibitors have been identified yet. The current lack of drugs for Chagas disease necessitates more R&D into the design and discovery of strong inhibitors of T. cruzi trans-sialidase.
Norman, Lashaunda Renea
This qualitative case study investigated the teaching strategies that improve science learning of African American students. This research study further sought the extent the identified teaching strategies that are used to improve African American science learning reflect culturally responsive teaching. Best teaching strategies and culturally responsive teaching have been researched, but there has been minimal research on the impact that both have on science learning, with an emphasis on the African American population. Consequently, the Black-White achievement gap in science persists. The findings revealed the following teaching strategies have a positive impact on African American science learning: (a) lecture-discussion, (b) notetaking, (c) reading strategies, (d) graphic organizers, (e) hands-on activities, (f) laboratory experiences, and (g) cooperative learning. Culturally responsive teaching strategies were evident in the seventh-grade science classrooms observed. Seven themes emerged from this research data: (1) The participating teachers based their research-based teaching strategies used in the classroom on all of the students' learning styles, abilities, attitudes towards science, and motivational levels about learning science, with no emphasis on the African American student population; (2) The participating teachers taught the state content standards simultaneously using the same instructional model daily, incorporating other content areas when possible; (3) The participating African American students believed their seventh-grade science teachers used a variety of teaching strategies to ensure science learning took place, that science learning was fun, and that science learning was engaging; (4) The participating African American students genuinely liked their teacher; (5) The participating African American students revealed high self-efficacy; (6) The African American student participants' parents value education and moved to Success Middle School
Moreno, S Andrea; Concepción, Juan Luis; Nava, Mayerly; Molinari, Jesús
In Venezuela, horses are indispensable for extensive cattle raising, and extensive cattle raising prevails in all regions. This determines the numerical relationship between horses and cattle (r = 0.93) to be relatively constant nationwide. At regional level, the average extension of cattle ranches varies greatly. However, in relation to the area covered by pastures, the numbers of horses (r = 0.95) and cattle (r = 0.93) are relatively uniform nationwide. Water buffalo occupy small fractions of the territory; therefore, their numbers are related to the area of pastures less strongly (r = 0.56). There is no information on the numerical relationship between the numbers of horses and water buffalo. In the Llanos region of the country, equine trypanosomiasis is responsible for a high mortality in horses, causing considerable financial losses to cattle ranches. So far, such losses have not been assessed. For this region, in 2008, it can be calculated that: (1) with no treatment, losses owing to horse mortality caused by this hemoparasitosis would have amounted to US$7,486,000; (2) the diagnosis and treatment of affected horses would have required an investment of US$805,000; and (3) in terms of horses saved, this investment would have resulted in benefit of US$6,232,000. Therefore, for every monetary unit invested, there would be a benefit 7.75 times greater, this ratio being applicable to any year and all regions of the country. It follows that the profitability of investing in the diagnosis and treatment of equine trypanosomiasis is guaranteed.
Balasegaram, Manica; Harris, Steve; Checchi, Francesco; Ghorashian, Sara; Hamel, Catherine; Karunakara, Unni
OBJECTIVE: To compare the effectiveness of melarsoprol and eflornithine in treating late-stage Gambian trypanosomiasis in the Republic of the Congo. METHODS: We analysed the outcomes of death during treatment and relapse within 1 year of discharge for 288 patients treated with eflornithine, 311 patients treated with the standard melarsoprol regimen and 62 patients treated with a short-course (10-day) melarsoprol regimen between April 2001 and April 2005. FINDINGS: A total of 1.7% (5/288) of patients treated with eflornithine died compared with 4.8% (15/311) of those treated with standard melarsoprol and 6.5% (4/62) of those treated with short-course melarsoprol. Patients treated with eflornithine tended to be younger and were more likely to have trypanosomes or higher white blood cell counts in their cerebrospinal fluid. The cumulated incidence of relapse among patients who attended at least one follow-up visit 1 year after discharge was 8.1% (11/136) for those treated with eflornithine, 14% (36/258) for those treated with standard melarsoprol and 15.5% (9/58) for those treated with shortcourse melarsoprol. In a multivariate analysis, when compared with eflornithine, standard melarsoprol was found to be a risk factor for both death (odds ratio (OR) = 2.87; 95% confidence interval (CI) = 1.03-8.00) and relapse (hazard ratio (HR) = 2.47; 95% CI = 1.22-5.03); when compared with eflornithine, short-course melarsoprol was also found to be a risk factor for death (OR = 3.90; 95% CI = 1.02-14.98) and relapse (HR = 6.65; 95% CI = 2.61-16.94). CONCLUSION: The effectiveness of melarsoprol treatment appears to have diminished. Eflornithine seems to be a better first-line therapy for treating late-stage Gambian trypanosomiasis in the Republic of the Congo. PMID:17128358
Faerstein, E; Szklo, M; Rosenshein, N
The authors conducted a case-control study among premenopausal women in the Baltimore, Maryland, area to examine the associations of uterine leiomyoma with ethnicity and hormone-related characteristics. Cases of uterine leiomyoma (n = 318) were surgically or sonographically first confirmed between January 1990 and June 1993. A total of 394 controls were selected from women who were visiting their gynecologist for a routine checkup. Data were collected through telephone interviews and abstraction of medical records; 77.8% of eligible cases and 78.0% of eligible controls were interviewed. Positive adjusted associations were observed between risk of uterine leiomyoma and self-described African-American ethnicity (vs. Whites: odds ratio (OR) = 9.4; 95% confidence interval (CI): 5.7, 15.7), early menarche (<11 years vs. >13 years: OR = 2.4; 95% CI: 1.1, 5.6), and high body mass index (upper quartile vs. lower quartile: OR = 2.3; 95% CI: 1.4, 3.8). Inverse associations were observed with use of oral contraceptives (current use vs. never use: OR = 0.2, 95% CI: 0.1, 0.6) and duration of smoking (> or =19 years vs. never: OR = 0.6; 95% CI: 0.4, 1.1). Younger ages at infertility diagnosis and at first and last childbirth were more common among cases; however, analyses of data on tumor location suggested that these associations represent predominantly consequences of uterine leiomyoma. These results suggest that development of uterine leiomyoma is associated with increased exposure to ovarian hormones. Possible reasons for the very elevated risk among African-American women need further investigation.
Ghafoor, Asma; Jemal, Ahmedin; Cokkinides, Vilma; Cardinez, Cheryll; Murray, Taylor; Samuels, Alicia; Thun, Michael J
The American Cancer Society provides estimates on the number of new cancer cases and deaths, and compiles health statistics on African Americans in a biennial publication, Cancer Facts and Figures for African Americans. The compiled statistics include cancer incidence, mortality, survival, and lifestyle behaviors using the most recent data on incidence and survival from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program, mortality data from the National Center for Health Statistics (NCHS), and behavioral information from the Behavior Risk Factor Surveillance System (BRFSS), Youth Risk Behavior Surveillance System (YRBSS), and National Health Interview Survey (NHIS). It is estimated that 132,700 new cases of cancer and 63,100 deaths will occur among African Americans in the year 2003. Although African Americans have experienced higher incidence and mortality rates of cancer than whites for many years, incidence rates have declined by 2.7 percent per year in African-American males since 1992, while stabilizing in African-American females. During the same period, death rates declined by 2.1 percent and 0.4 percent per year among African-American males and females, respectively. The decrease in both incidence and death rates from cancer among African-American males was the largest of any racial or ethnic group. Nonetheless, African Americans still carry the highest cancer burden among US racial and ethnic groups. Most cancers detectable by screening are diagnosed at a later stage and survival rates are lower within each stage of disease in African Americans than in whites. The extent to which these disparities reflect unequal access to health care versus other factors is an active area of research.
Paliwal, Sarvesh K; Verma, Ankita Narayan; Paliwal, Shailendra
Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness.
Omolo, Maurice O; Hassanali, Ahmed; Mpiana, Serge; Esterhuizen, Johan; Lindh, Jenny; Lehane, Mike J; Solano, Philippe; Rayaisse, Jean Baptiste; Vale, Glyn A; Torr, Steve J; Tirados, Inaki
We are attempting to develop cost-effective control methods for the important vector of sleeping sickness, Glossina fuscipes spp. Responses of the tsetse flies Glossina fuscipes fuscipes (in Kenya) and G. f. quanzensis (in Democratic Republic of Congo) to natural host odours are reported. Arrangements of electric nets were used to assess the effect of cattle-, human- and pig-odour on (1) the numbers of tsetse attracted to the odour source and (2) the proportion of flies that landed on a black target (1x1 m). In addition responses to monitor lizard (Varanus niloticus) were assessed in Kenya. The effects of all four odours on the proportion of tsetse that entered a biconical trap were also determined. Sources of natural host odour were produced by placing live hosts in a tent or metal hut (volumes approximately 16 m(3)) from which the air was exhausted at approximately 2000 L/min. Odours from cattle, pigs and humans had no significant effect on attraction of G. f. fuscipes but lizard odour doubled the catch (P<0.05). Similarly, mammalian odours had no significant effect on landing or trap entry whereas lizard odour increased these responses significantly: landing responses increased significantly by 22% for males and 10% for females; the increase in trap efficiency was relatively slight (5-10%) and not always significant. For G. f. quanzensis, only pig odour had a consistent effect, doubling the catch of females attracted to the source and increasing the landing response for females by approximately 15%. Dispensing CO(2) at doses equivalent to natural hosts suggested that the response of G. f. fuscipes to lizard odour was not due to CO(2). For G. f. quanzensis, pig odour and CO(2) attracted similar numbers of tsetse, but CO(2) had no material effect on the landing response. The results suggest that identifying kairomones present in lizard odour for G. f. fuscipes and pig odour for G. f. quanzensis may improve the performance of targets for controlling these species.
Natural products extracts from 522 plants collected from different parts of the North America were screened in vitro against trypamastigote forms of Trypanosoma brucei. The active extracts(150)with >90% inhibition at 20ug/mL concentrations from the plants namely, Alnus rubra, Hoita macrostachya, S...
Subramanyam, V R; Mtitimila, E; Hart, C A; Broadhead, R L
Three cases of cryptococcal meningitis in Malawian children aged 6 weeks, 3 years and 9 years are described. Only 23 cases of cryptococcal meningitis in children have been described previously, but in children from Europe and the USA. These are therefore the first cases of cryptococcosis to be described in African children.
Williams, B; Campbell, C
The epidemic of HIV/AIDS is at an advanced stage in many African countries, but little attention has been given to the impact that this will have in industrial settings. Using the Southern African mining industry as a case study, the authors consider the state of the HIV epidemic and discuss programs that have been undertaken to manage HIV. They critically analyze the reasons current interventions have had little impact on HIV among mine workers, tracing the lack of success to neglect of the social and community contexts within which HIV transmission takes place, as well as the lack of attention to the psychosocial processes and mechanisms underlying disease transmission. Finally, they present an intervention that aims to address the limitations of existing industrial programs and improve the management of sexually transmitted diseases (STDs), including HIV, in a particular occupational setting through creating alliances between a wide range of community stakeholders. The intervention aims not only to reduce STDs, promote awareness of HIV risks, and distribute condoms, as existing programs have done, but also to address the broader social, cultural, and community contexts that facilitate HIV transmission.
Masumu, J; Geysen, D; Van den Bossche, P
In order to verify whether the low impact on livestock production in endemic areas is related to a low number of trypanosome strains circulating in livestock, 37 Trypanosoma congolense isolates collected from cattle in 11 sites in an endemic trypanosomiasis area in Eastern Zambia were characterised for genotype variability using a modified amplified fragment length polymorphism technique (AFLP). Isolates were further cloned to evaluate the occurrence of mixed infections in individuals. The results obtained revealed a high genotype diversity (94.6%) among these isolates. Apart from one site, all isolates gave different AFLP profiles in each of the sites. When clones were compared, three (8%) of the 37 isolates had mixed infections. These results indicate the circulation of a high number of strains in this trypanosomiasis endemic area despite the low impact the disease has on livestock production.
Thompson, LaTasha R.; Lewis, Bradford F.
The mathematics success of African American male adolescents has been given limited attention. Most often, African American males are viewed in terms of their failure as opposed to their success. This tendency to focus almost exclusively on African American failure is a debilitating feature of extant literature and it constrains our understanding…
Haines, Lee R; Hancock, Robert E W; Pearson, Terry W
Nine biochemically distinct cationic antimicrobial peptides were tested in vitro for their effects on bloodstream forms and procyclic (insect) forms of African trypanosomes, the protozoan parasites that cause African sleeping sickness in humans and trypanosomiasis in domestic animals. At low concentrations, one peptide completely inhibited growth of bloodstream forms, one inhibited procyclic forms, and five inhibited both trypanosome life cycle stages. The peptides were also tested on Sodalis glossinidius, a bacterial symbiont of tsetse flies. S. glossinidius was highly resistant to seven of the nine peptides, including both that specifically inhibited either bloodstream or procyclic forms and three of the five that inhibited both trypanosome life cycle stages. The results indicate that several of these peptides may be ideal candidates for therapy of trypanosome infected mammals or for transgenic expression in S. glossinidius as a strategy for inhibiting trypanosome survival, development, and maturation in tsetse and interference with transmission of African sleeping sickness.
Kawai, Makoto; O'Hara, Ruth; Einen, Mali; Lin, Ling; Mignot, Emmanuel
Study Objectives: Although narcolepsy affects 0.02–0.05% of individuals in various ethnic groups, clinical presentation in different ethnicities has never been fully characterized. Our goal was to study phenotypic expression across ethnicities in the United States. Design/Setting: Cases of narcolepsy from 1992 to 2013 were identified from searches of the Stanford Center for Narcolepsy Research database. International Classification of Sleep Disorders, Third Edition diagnosis criteria for type 1 and type 2 narcolepsy were used for inclusion, but subjects were separated as with and without cataplexy for the purpose of data presentation. Information extracted included demographics, ethnicity and clinical data, HLA-DQB1*06:02, polysomnography (PSG), multiple sleep latency test (MSLT) data, and cerebrospinal fluid (CSF) hypocretin-1 level. Patients: 182 African-Americans, 839 Caucasians, 35 Asians, and 41 Latinos with narcolepsy. Results: Sex ratio, PSG, and MSLT findings did not differ across ethnicities. Epworth Sleepiness Scale (ESS) score was higher and age of onset of sleepiness earlier in African Americans compared with other ethnicities. HLA-DQB1*06:02 positivity was higher in African Americans (91.0%) versus others (76.6% in Caucasians, 80.0% in Asians, and 65.0% in Latinos). CSF hypocretin-1 level, obtained in 222 patients, was more frequently low (≤ 110 pg/ml) in African Americans (93.9%) versus Caucasians (61.5%), Asians (85.7%) and Latinos (75.0%). In subjects with low CSF hypocretin-1, African Americans (28.3%) were 4.5 fold more likely to be without cataplexy when compared with Caucasians (8.1%). Conclusions: Narcolepsy in African Americans is characterized by earlier symptom onset, higher Epworth Sleepiness Scale score, higher HLA-DQB1*06:02 positivity, and low cerebrospinal fluid hypocretin-1 level in the absence of cataplexy. In African Americans, more subjects without cataplexy have type 1 narcolepsy. Citation: Kawai M, O'Hara R, Einen M, Lin L
van Dyk, Leana; Springer, Priscilla; Kidd, Martin; Steyn, Nellie; Solomons, Regan; van Toorn, Ronald
We investigated familial and environmental risk factors in a cohort of South African children diagnosed with attention-deficit hyperactivity disorder (ADHD). A prospective, hospital-based case control study was conducted comprising 50 children diagnosed with ADHD and 50 matched non-ADHD controls. The adjusted effect of familial-environmental risk factors on ADHD was determined by systematic assessment. Birth complications, parental psychiatric disorder, maternal ADHD, early childhood trauma, and nonmaternal child care were significant risk factors for ADHD. Prolonged breastfeeding was found to be protective. In a multivariable logistic regression model, 5 criteria (birth complications, breastfeeding <3 months, at least 1 parent with tertiary education, presence of parental psychiatric disorder, and nonmaternal primary caregiver) differentiated ADHD from non-ADHD controls with a sensitivity and specificity of 74% and 86%, respectively. We found a correlation between certain familial and environmental risk factors and ADHD. A 5-criterion multivariable logistic regression model may offer clinical guidance in ADHD diagnosis.
McNeal, Gloria J
The purpose of this investigation, using case study methodology, was to explore the end of life issues and to give meaning to the biopsychosocial experiences of the study participant, an adult African American female patient diagnosed with Cystic Fibrosis. Two theoretical frameworks were used to guide the investigation of the study: Kubler-Ross Model of the Stages of Dying and the Conceptual Framework for Palliative Care Practice. Data analysis included review of medical records and patient journals, interviews, observations and clinical assessment. The findings indicated that end of life issues can be articulated within the context of a palliative care framework and that the biopsychosocial experiences of the dying person acquire meaning when situated within life history, ethical values and metaphysical belief systems.
Mian, D B; Nguessan, K L P; Aissi, G; Boni, S
Amniotic band syndrome (ABS) is a fetal congenital malformation, affecting mainly the limbs, but also the craniofacial area and internal organs. Two mains pathogenic mechanisms are proposed in its genesis. Firstly the early amnion rupture (exogenous theory) leading to fibrous bands, which wrap up the fetal body; secondly, the endogenous theory privileges vascular origin, mesoblastic strings not being a causal agent. The authors believe that the second theory explain the occurrence of ABS. The outcome of the disease during pregnancy depends on the gravity of the malformations. Interruption of the pregnancy is usually proposed when diagnosis of severe craniofacial and visceral abnormalities is confirmed. Whereas minor limb defects can be repaired with postnatal surgery. In case of an isolated amniotic band with a constricted limb, in utero lysis of the band can be considered to avoid a natural amputation. In an African country, such treatment is not possible as far as the antenatal diagnosis.
Guillocheau, F.; Dauteuil, O.
Several attempts have been made to identify different paleosurfaces since the classical works of Lester King (1942, 1949) at the scale of Africa. Thermochronologists and river geomorphologists criticized this approach. This criticism mainly concerned the age of the surfaces, that were (1) poorly constraints and (2) a king of catechism on which all studies must refer. Nevertheless, those planation surfaces exist and are key features of the present-day morphology of Africa. In details, real planation surfaces are (1) no more than two or three and (2) can be deformed and then merged together. Those surfaces are incised by large smooth valleys, called pediments or glacis (with some semantic differences between English and French-speaking geomorphologists). Those pediments formed a pre-network of rivers, later re-incised by the present-day incised narrow valleys. Those different morphological structures can be dated using (1) their merge with sedimentary basins, (2) their relationship with the different types of dated weathering periods and (3) their relationships with volcanism. They also can be used as a proxy of the deformation based on the differences of elevation of the planations surfaces or on the shape of the pediments. From the Orange River to the Cameroon Volcanic Line, including the Congo Cuvette, two planations surfaces were identified (the Bauxitic or African surface, the intermediate surface), at least two generations of pediment valleys and the present-day incised valley network. The African surface is of Late Paleocene to Middle Eocene age with a climax during this last period and two major periods of uplift can be identified and mapped (1) Late Eocene-Early Oligocene and (2) Lower Miocene. Most of the relief is fossil since that period, excepted in the Angola Mountains were deformations are active during Plio-Pleistocene times. Those uplifts of smoother, most of the time weathered, relief than today, had important consequences on the petrology and the
Transformation and Institutional Quality Management within a South African University: A Case Study of the University of the Orange Free State. Improving the Managerial Effectiveness of Higher Education Institutions.
Strydom, A. H.; Holtzhausen, Somarie
This case study evaluated the development, partial implementation, and review of an institutional and operational approach to quality management that was developed, during a decade of radical political change, at the University of the Orange Free State, resulting in the rapid transformation of higher education institutions in South African. Phase…
Meyer, Britta S; Indermaur, Adrian; Ehrensperger, Xenia; Egger, Bernd; Banyankimbona, Gaspard; Snoeks, Jos; Salzburger, Walter
The species flocks of cichlid fishes in the East African Great Lakes are the largest vertebrate adaptive radiations in the world and illustrious textbook examples of convergent evolution between independent species assemblages. Although recent studies suggest some degrees of genetic exchange between riverine taxa and the lake faunas, not a single cichlid species is known from Lakes Tanganyika, Malawi and Victoria that is derived from the radiation associated with another of these lakes. Here, we report the discovery of a haplochromine cichlid species in Lake Tanganyika, which belongs genetically to the species flock of haplochromines of the Lake Victoria region. The new species colonized Lake Tanganyika only recently, suggesting that faunal exchange across watersheds and, hence, between isolated ichthyofaunas, is more common than previously thought.
Case, Jennifer M.; Fraser, Duncan M.; Kumar, Anil; Itika, Ambrose
Curriculum reform is a key topic in the engineering education literature, but much of this discussion proceeds with little engagement with the impact of the local context in which the programme resides. This article thus seeks to understand the influence of local contextual dynamics on curriculum reform in engineering education. The empirical study is a comparative analysis of the context for curriculum reform in three different chemical engineering departments on the African continent, located in Kenya, Tanzania and South Africa. All three departments are currently engaged in processes of curriculum reform, but the analysis shows how the different contexts in which these efforts are taking place exert strong shaping effects on the processes and outcomes for that reform.
No single traditional discipline can adequately supply answers to the many unresolved questions in African art history. Because of the aesthetic, cultural, historical, and, not infrequently, political biases, already built into the conception and development of Western art history, the discipline of art history as defined and practiced in the West…
Garrard, David J.
The diversity of African Pentecostalism, its early colonial and missionary history and its current characteristics are described and analysed. Reference is made to methods of training and forms of leadership, and suggestions are made about the reasons for its growth and persistence. (Contains 19 notes.)
Lange, M; Siemen, H; Blome, S; Thulke, H-H
African swine fever (ASF) is a highly lethal viral disease of domestic pigs and wild boar. ASF was introduced into the southern Russian Federation in 2007 and is now reported to be spreading in populations of wild and domestic suids. An endemic situation in the local wild boar population would significantly complicate management of the disease in the livestock population. To date no sound method exists for identifying the characteristic pattern of an endemic situation, which describes infection persisting from generation to generation in the same population. To support urgent management decisions at the wildlife-livestock interface, a new algorithm was constructed to test the hypothesis of an endemic disease situation in wildlife on the basis of case reports. The approach described here uses spatial and temporal associations between observed diagnostic data to discriminate between endemic and non-endemic patterns of case occurrence. The algorithm was validated with data from an epidemiological simulation model and applied to ASF case data from southern Russia. Based on the algorithm and the diagnostic data available, the null hypothesis of an endemic situation of ASF in wild boar of the region was rejected.
Breurec, Sébastien; Vanel, Noémie; Bata, Petulla; Chartier, Loïc; Farra, Alain; Favennec, Loïc; Franck, Thierry; Giles-Vernick, Tamara; Gody, Jean-Chrysostome; Luong Nguyen, Liem Binh; Onambélé, Manuella; Rafaï, Clotaire; Razakandrainibe, Romy; Tondeur, Laura; Tricou, Vianney; Sansonetti, Philippe; Vray, Muriel
Background In Sub-Saharan Africa, infectious diarrhea is a major cause of morbidity and mortality. A case-control study was conducted to identify the etiology of diarrhea and to describe its main epidemiologic risk factors among hospitalized children under five years old in Bangui, Central African Republic. Methods All consecutive children under five years old hospitalized for diarrhea in the Pediatric Complex of Bangui for whom a parent’s written consent was provided were included. Controls matched by age, sex and neighborhood of residence of each case were included. For both cases and controls, demographic, socio-economic and anthropometric data were recorded. Stool samples were collected to identify enteropathogens at enrollment. Clinical examination data and blood samples were collected only for cases. Results A total of 333 cases and 333 controls was recruited between December 2011 and November 2013. The mean age of cases was 12.9 months, and 56% were male. The mean delay between the onset of first symptoms and hospital admission was 3.7 days. Blood was detected in 5% of stool samples from cases. Cases were significantly more severely or moderately malnourished than controls. One of the sought-for pathogens was identified in 78% and 40% of cases and controls, respectively. Most attributable cases of hospitalized diarrhea were due to rotavirus, with an attributable fraction of 39%. Four other pathogens were associated with hospitalized diarrhea: Shigella/EIEC, Cryptosporidium parvum/hominis, astrovirus and norovirus with attributable fraction of 9%, 10%, 7% and 7% respectively. Giardia intestinalis was found in more controls than cases, with a protective fraction of 6%. Conclusions Rotavirus, norovirus, astrovirus, Shigella/EIEC, Cryptosporidium parvum/hominis were found to be positively associated with severe diarrhea: while Giardia intestinalis was found negatively associated. Most attributable episodes of severe diarrhea were associated with rotavirus
Suggests sources of information for African American History Month for library media specialists who work with students in grades four through eight. Gale Research's "African-American Reference Library," which includes "African-America Biography,""African-American Chronology," and "African-American Almanac,"…
Langridge, W. P.; Kernaghan, R. J.; Glover, P. E.
In this survey of recent ecological research on the main vectors of trypanosomiasis in those countries of East, Central and West Africa that are not predominantly French-speaking, the authors, after outlining the distribution of tsetse flies and the type of country in which they occur, discuss the direct and indirect effects of climate on these insects—particularly on their physiological water balance and on pupal fat reserves—and their recent advances into new areas. They review the considerable work that has been done on the resting habits and breeding-sites of different Glossina species, knowledge of which is important for effective control, and research on predators of pupae and adult flies and on the feeding activity of tsetse flies. Means of assessing populations and various factors affecting the size and nutritional status of tsetse flies are also discussed, as is the effect on the fly population of artificial changes in the habitat. Finally, a plea is made for a revision of present methods of land use and stock management, if full advantage is to be taken of achievements in fly control. PMID:13928678
Rodriguez, Juan Bautista
Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3β-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas disease. These metabolites are crucial; consequently, the enzymes implicated in catalyzing their formation constitute interesting molecular targets for drug design. Selective inhibition of an enzyme associated to the ergosterol biosynthesis will produce T. cruzi cell arrest. Trypanosomatids, fungi, and yeasts have need of these endogenous sterols for cell viability and growth. In fact, some effective ergosterol biosynthesis inhibitors bearing suitable pharmacokinetic properties in mammals have become putative antiparasitic agents by inducing almost complete parasitological cure in both acute and chronic experimental Chagas disease. WC-9 (compound 7; 4-phenoxyphenoxyethyl thiocyanate) holds our attention bearing in mind that this compound exhibits ED50values at the low nanomolar range against the clinically more relevant replicative form of T. cruzi (amastigotes). The cellular activity of WC-9 is due to an exhaustion of endogenous sterols demonstrating a blockade of the biosynthetic pathway at a pre-squalene level.
Qureshi, Ayman M.; Makhdomi, Khalid; Stones, William
Prostate cancer is the most common noncutaneous cancer in males. Men of African origin are at a significantly higher risk as reflected in the higher incidence and mortality rates in this racial group. Metastases incidence increases parallel to serum levels of prostate-specific antigen (PSA), contributing significantly to morbidity and mortality. Staging of the disease involves bone scans, which are sensitive in detecting skeletal metastases. Suggestions that these scans may be omitted in some situations in patients with low prostate specific antigen levels have drawn attention to the matter. In this case-control study, using radiology and pathology records, a registry of prostate cancer patients recorded as being of dark-skinned ethnicity was obtained. Images were presented to image reviewers blinded to the PSA level, to determine the presence of skeletal metastases. The risk factor for the outcome of interest (skeletal metastases) was PSA level above 20 ng/mL. The reliability of image reporting was also assessed. Of the 122 patients, skeletal metastases were present in 50 (41%) while these were absent in 72 (59%). The prevalence of metastases among the high PSA group was 55.9% [95% confidence interval (CI) 44.1–67.7%] and among the normal/low PSA group was 22.2% (95% CI 11.1–33.3%). The odds ratio (OR) for skeletal metastases in the exposed (high PSA) group was 4.4 (95% CI, 2.01–9.78.) Intraobserver agreement on image interpretation was 88.5% with a Kappa statistic of 0.76. A relatively higher prevalence of skeletal metastasis is seen in regional dark-skinned African males with prostate cancer at both low and high prostate specific antigen levels. Bone scanning in this population should therefore, be considered even at PSA levels below 20 ng/mL. PMID:28217016
Rohrich, Rod J; Muzaffar, Arshad R
Because of the increasing popularity of rhinoplasty in the African-American patient, we delineate how a rhinoplasty surgeon can perform this challenging technique to obtain uniform and consistent results. First, we address how one can appreciate and analyze the various aesthetic concepts of beauty and the unique anatomic characteristics of the African-American nose. Second, we present a pragmatic, systematic analysis of the African-American nose. Last, we describe the techniques consistently used to modify the African-American nose while achieving or maintaining facial harmony using the open approach to rhinoplasty. Specific case analyses are presented to demonstrate utilization of the technique.
Abdi, Ali A., Ed.; Puplampu, Korbla P., Ed.; Dei, George J. Sefa, Ed.
Containing both theoretical discussions of globalization and specific case analyses of individual African countries, this collection of essays examines the intersections of African education and globalization with multiple analytical and geographical emphases and intentions. The 11 essays critically analyze the issues from historical, cultural,…
Mims, Adrian B.
This case study evaluated the significance of implementing an enrichment mathematics course during the summer to rising African American ninth graders entitled, "Geometry Honors Preview." In the past, 60 to 70 percent of African American students in this school district had withdrawn from Geometry Honors by the second academic quarter. This study…
Randrianantoandro, Tiana N; Kono, Hiroichi; Kubota, Satoko
Pig production in Madagascar is not sufficient for domestic consumption. Unfortunately, African swine fever (ASF), which is a severe disease, is endemic in Madagascar and constitutes a constant threat for farmers. Therefore, ASF must be eradicated in order to guarantee the development of pig production. One of the main strategies in controlling ASF is stamping out which requires the farmers' collaboration in reporting cases or suspected cases. The objective of this study was to estimate the proportion of farmers who knowingly sell ASF-infected meat without reporting. Since selling ASF-infected meat is prohibited by the government, we used the item count technique (ICT), an indirect questioning technique appropriate for measuring the proportion of people engaged in sensitive behavior, for one subsample, while another subsample was asked directly whether they sell ASF-infected meat. Based on the ICT, approximately 73.2% of farmers who have experienced ASF sell the ASF-infected meat. This estimate was not statistically different from that obtained by direct questioning. In the 28% of interviewed farmers who believe ASF can affect humans, the ICT yielded a higher estimate than did direct questioning, indicating that pig farmers who sell ASF-infected meat hide that fact because of their belief that infected meat might harm human consumers, not because of the law. The ICT was thus a suitable technique to address the problem of sensitive behavior. In the case of ASF outbreaks, the Malagasy government should enforce the law more strictly and provide compensation as incentive for reporting cases.
Wooten, Cynthia Brooks
The purpose of this qualitative study was to investigate ways in which six teachers in the intermediate grades at one urban and one rural school enabled their African American male students to be successful in their literacy efforts. It was my assumption that successful teachers of African American males would also be teachers who integrated…
Benson, Shanelle R.
Purpose. The purpose of this study was to determine, to what degree, African American teachers in five selected, urban charter schools in New York performed the historical roles of counselor, advocate, disciplinarian, surrogate parent, and role model in, to determine how African American Teachers perceived the importance of performing the…
Neelapu, Nageswara R R; Srimath-Tirumala-Peddinti, Ravi C P K; Nammi, Deepthi; Pasupuleti, Amita C M
The discovery and exploitation of new drug targets is a key focus for both the pharmaceutical industry and academic research. To provide an insight into trends in the exploitation of new drug targets, we have analysed different methods during the past six decades and advances made in drug target discovery. A special focus remains on different methods used for drug target discovery on infectious diseases such as Tuberculosis, Gastritis, Malaria, Trypanosomiasis and Leishmaniasis. We herewith provide a paradigm that is can be used for drug target discovery in the near future.
Semballa, S; Okomo-Assoumou, M C; Holzmuller, P; Büscher, P; Magez, S; Lemesre, J L; Daulouede, S; Courtois, P; Geffard, M; Vincendeau, P
Antibodies (Ab) directed against a tryptophan-like epitope (WE) were previously detected in patients with human African trypanosomiasis (HAT). We investigated whether or not these Ab resulted from immunization against trypanosome antigen(s) expressing a WE. By Western blotting, we identified an antigen having an apparent molecular weight ranging from 60 to 65 kDa, recognized by purified rabbit anti-WE Ab. This antigen, present in trypomastigote forms, was absent in procyclic forms and Trypanosoma cruzi trypomastigotes. Using purified variable surface glycoproteins (VSG) from various trypanosomes, we showed that VSG was the parasite antigen recognized by these rabbit Ab. Anti-WE and anti-VSG Ab were purified from HAT sera by affinity chromatography. Immunoreactivity of purified antibodies eluted from affinity columns and of depleted fractions showed that WE was one of the epitopes borne by VSG. These data underline the existence of an invariant WE in the structure of VSG from several species of African trypanosomes.
Jacobs, Robert T.; Nare, Bakela; Phillips, Margaret A.
African sleeping sickness is endemic in sub-Saharan Africa where the WHO estimates that 60 million people are at risk for the disease. Human African trypanosomiasis (HAT) is 100% fatal if untreated and the current drug therapies have significant limitations due to toxicity and difficult treatment regimes. No new chemical agents have been approved since eflornithine in 1990. The pentamidine analog DB289, which was in late stage clinical trials for the treatment of early stage HAT recently failed due to toxicity issues. A new protocol for the treatment of late-stage T. brucei gambiense that uses combination nifurtomox/eflornithine (NECT) was recently shown to have better safety and efficacy than eflornithine alone, while being easier to administer. This breakthrough represents the only new therapy for HAT since the approval of eflornithine. A number of research programs are on going to exploit the unusual biochemical pathways in the parasite to identify new targets for target based drug discovery programs. HTS efforts are also underway to discover new chemical entities through whole organism screening approaches. A number of inhibitors with anti-trypanosomal activity have been identified by both approaches, but none of the programs are yet at the stage of identifying a preclinical candidate. This dire situation underscores the need for continued effort to identify new chemical agents for the treatment of HAT. PMID:21401507
Gary, Tiffany L; Batts-Turner, Marian; Bone, Lee R; Yeh, Hsin-Chieh; Wang, Nae-Yuh; Hill-Briggs, Felicia; Levine, David M; Powe, Neil R; Hill, Martha N; Saudek, Christopher; McGuire, Maura; Brancati, Frederick L
The objective of the study was to determine the effectiveness and cost-effectiveness of primary care and community-oriented interventions in managing HbA1c, blood pressure, and lipids, and reducing hospitalizations and emergency room visits over 2 years. We describe an ongoing, randomized controlled trial of 542 urban African-Americans with type 2 diabetes ages 25 years and older who are members of a university-affiliated managed-care organization in Baltimore, MD. The participants are 74% female, have a mean age of 58 years, and 35% have yearly incomes greater than 7500 US dollars. Participants were randomized to one of two intervention groups for a period of 2 years: (1) usual medical care plus minimal telephone intervention implemented by a trained lay health educator (control group) or (2) usual medical care plus intensive intervention implemented by a nurse case manager (NCM)/community health worker (CHW) team. The intensive NCM/CHW team executes individual plans of care using evidence-based algorithms that focus on traditional diabetes self-management, screening and management of diabetes-related complications, and social issues surrounding diabetes care. Face-to-face NCM visits are conducted in the clinic once per year and CHW visits are conducted in the participant's home one to three times per year, both with additional follow-up contacts as needed. Written and verbal feedback (when necessary) is provided to the participant's primary care physician. All participants are expected to attend a 24-month follow-up visit where data are collected by interviewers blinded to intervention assignment. As of May 1, 2003, recruitment is complete, interventions are being fully implemented, and 24-month follow-up visits are beginning. Baseline sociodemographic characteristics, health-care utilization, health behaviors, and clinical characteristics of the study population are reported. This study is designed to test the hypothesis that a primary-care-based NCM plus CHW
Introduction American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics. Methods In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status. Results More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs. Conclusions These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women. PMID:22480149
There is a need to reassess the role of the trypanosomiases, both human and animal, in African ecology and economy. Withdrawal of control services from the Congo basin was followed by a resurgence of infection from ancient foci, many of them thought to have been extinguished. Successful elimination of Glossina in savanna habitats has sometimes been followed by reinvasion causing massive epizootics. Elsewhere continued recession of the tsetse fly has been followed by cattle population growth which is periodically interrupted by catastrophic pasture famines. Efficiency of control rather than large-scale eradication should be the immediate aim. Efficient control keeps trypanosomiasis at a tolerable level in relation to the competence of medical and veterinary services and ensures that the beneficial effects of disease in maintaining a balance between natural resource potential of the continent and the energy output of its inhabitants, are retained until they can be replaced by new social and economic controls integrated in local cultures. Many ideas about control planning formulated before 1960 are now irrelevant. To provide foundations for a new policy 3 requirements must be fulfilled. The first is to understand the nature of natural foci of infection of trypanosomiasis; the second is to collate knowledge of land-use potentials of the fly-belts; the third is to find a means of integrating information to achieve balanced control programmes. To do this a formal mathematical study of the epidemiology and epizootiology of the trypanosomiases should be initiated. PMID:5307600
Schmidt, Nancy J.
This report discusses the 1974 African Outreach Workshop planned and coordinated by the African Studies Program at the University of Illinois at Urbana-Champaign. Its major aim was to assist teachers in developing curriculum units on African using materials available in their local community. A second aim was for the African Studies Program to…
Hart, Ayanna; Spangler, Earl
This book introduces African-American history and culture to children. The first Africans in America came from many different regions and cultures, but became united in this country by being black, African, and slaves. Once in America, Africans began a long struggle for freedom which still continues. Slavery, the Civil War, emancipation, and the…
Kannen, Vinicius; de Oliveira, Enio C.; Motta, Bruno Zene; Chaguri, Annuar Jose; Brunaldi, Mariângela Ottoboni; Garcia, Sérgio B.
Background Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats. Methods Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards. Results No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas’ megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2nd wk onward, which ensued having the colon myenteric denervation significantly induced. Conclusion/Significance Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research. PMID:25884710
Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV-I-associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical, pathological and immunovirological study of 14 cases and a review of the African ATL cases.
Fouchard, N; Mahe, A; Huerre, M; Fraitag, S; Valensi, F; Macintyre, E; Sanou, F; de The, G; Gessain, A
Cutaneous T cell lymphomas (CTCL) are rare lymphoproliferative diseases, which are frequently suspected to be of viral origin. As very few data were available concerning cutaneous T cell lymphomas in tropical Africa, we undertook a clinical, histopathological, immunological and viro-molecular study of patients with a clinical diagnosis of cutaneous lymphoma, in Bamako, Mali. While prior to this study, no case of CTCL had been reported in this country, 14 patients (five women, nine men; mean age 58 years) with a diagnosis of cutaneous lymphoma were seen over a period of 30 months (1992-1994) in the only dermatological department in Mali. Clinically, the most frequent pattern was an infiltrated erythrodermia similar to Sezary syndrome. Nodular lesions and/or plaques were rarely observed. All these cutaneous tumors were T cell lymphoproliferations, only one expressing the CD8+ antigen. A comprehensive analysis of all the available data permitted characterization of three cases of adult T cell leukemia/lymphoma (ATL) associated with HTLV-I (one definitive case, of leukemic type, with demonstration of clonal integration of HTLV-I proviral genome and two probable ATL cases), three cases of Sezary syndrome (SS), two cases of mycosis fungoides (MF) and five cases of pleomorphic cutaneous lymphoma. In one case, the differentiation between MF and pleomorphic cutaneous lymphoma could not be established. HTLV-I serological and/or molecular markers were restricted to the three ATL cases. From the unique definitive ATL case, a T cell line was established from culture of peripheral blood mononuclear cells and sequence analysis of the env gene and the U3-LTR region demonstrated that the virus present in this patient belonged to the cosmopolitan subtype A. Thus, we report here the first evidence of HTLV-I infection and associated ATL in Mali. This is the second ATL case described for the whole Sahelian region (one ATL of the lymphoma type was reported previously in a Mauritanian
Li, Yu; Millikan, Robert C; Bell, Douglas A; Cui, Lisa; Tse, Chiu-Kit J; Newman, Beth; Conway, Kathleen
Introduction Epidemiologic studies have not shown a strong relationship between blood levels of polychlorinated biphenyls (PCBs) and breast cancer risk. However, two recent studies showed a stronger association among postmenopausal white women with the inducible M2 polymorphism in the cytochrome P450 1A1 (CYP1A1) gene. Methods In a population-based case-control study, we evaluated breast cancer risk in relation to PCBs and the CYP1A1 polymorphisms M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4). The study population consisted of 612 patients (242 African American, 370 white) and 599 controls (242 African American, 357 white). Results There was no evidence of strong joint effects between CYP1A1 M1-containing genotypes and total PCBs in African American or white women. Statistically significant multiplicative interactions were observed between CYP1A1 M2-containing genotypes and elevated plasma total PCBs among white women (P value for likelihood ratio test = 0.02). Multiplicative interactions were also observed between CYP1A1 M3-containing genotypes and elevated total PCBs among African American women (P value for likelihood ratio test = 0.10). Conclusions Our results confirm previous reports that CYP1A1 M2-containing genotypes modify the association between PCB exposure and risk of breast cancer. We present additional evidence suggesting that CYP1A1 M3-containing genotypes modify the effects of PCB exposure among African American women. Additional studies are warranted, and meta-analyses combining results across studies will be needed to generate more precise estimates of the joint effects of PCBs and CYP1A1 genotypes. PMID:15642161
Kamulegeya, Adriane; Kalyanyama, Boniphace M
Background Neoplasms of the oral maxillofacial area are an interesting entity characterized by differences in nomenclature and classification at different centers. We report neoplastic histopathological diagnoses seen at the departments of oral maxillofacial surgery of Muhimbili and Mulago referral hospitals in Tanzania and Uganda respectively over a 10-year period. Methods We retrieved histopathological reports archived at the departments of oral maxillofacial surgery of Muhimbili and Mulago referral hospitals in Tanzania and Uganda respectively over a 10-year period from June 1989–July 1999. Results In the period between June 1989 and July 1999, 565 and 1298 neoplastic oro-facial cases were retrieved of which 284 (50.53%) and 967 (74.54%) were malignant neoplasms at Muhimbili and Mulago hospitals respectively. Overall 67.28% of the diagnoses recorded were malignant with Kaposi's sarcoma (21.98%), Burkiits lymphoma (20.45%), and squamous cell carcinoma (15.22%) dominating that group while ameloblastoma (9.23%), fibromas (7.3%) and pleomorphic adenoma (4.95%) dominated the benign group. The high frequency of malignancies could be due to inclusion criteria and the clinical practice of selective histopathology investigation. However, it may also be due to higher chances of referrals in case of malignancies. Conclusion There is need to reexamine the slides in these two centers in order to bring them in line with the most recent WHO classification so as to allow for comparison with reports from else where. PMID:18651958
This article derives from a doctoral thesis in which a particular discourse was used as a 'paradigm case'. From this discourse an ethic set within a South African culture arose. Using many cultural 'voices' to aid the understanding of this narrative, the ethic shows that one can build on both a 'justice' and a 'care' ethic. With further development based on African culture one can take the ethic of care deeper and reveal 'layers of understanding'. Care, together with compassion, forms the foundation of morality. Nursing ethics has followed particular western moral philosophers. Often nursing ethics has been taught along the lines of Kohlberg's theory of morality, with its emphasis on rules, rights, duties and general obligations. These principles were universalistic, masculine and noncontextual. However, there is a new ethical movement among Thomist philosophers along the lines to be expounded in this article. Nurses such as Benner, Bevis, Dunlop, Fry and Gadow--to name but a few--have welcomed the concept of an 'ethic of care'. Gilligan's work gave a feminist view and situated ethics in the everyday aspects of responsiveness, responsibility, context and concern. Shutte's search for a 'philosophy for Africa' has resulted in finding similarities in Setiloane and in Senghor with those of Thomist philosophers. Using this African philosophy and a research participant's narrative, an African ethic evolves out of the African proverb: 'A person is a person through other persons', or its alternative rendering: 'I am because we are: we are because I am.' This hermeneutic narrative reveals 'the way affect imbues activity with ethical meaning' within the context of a black nursing sister in a rural South African hospital. It expands upon the above proverb and incorporates the South African constitutional idea of 'Ubuntu' (compassion and justice or humanness).
This is a qualitative case study of the experiences and perceptions of South African and especially international, African students living in university residences in South Africa. The concept, community, is used to interpret interview data. This community was characterised by ambivalent social relations: There was discrimination by South Africans…
Reisach, Ulrike; Weilemann, Mitja
South Africa desperately needs a comprehensive approach to fight HIV/AIDS. Education is crucial to reach this goal and Internet and e-learning could offer huge opportunities to broaden and deepen the knowledge basis. But due to the huge societal and digital divide between rich and poor areas, e-learning is difficult to realize in the townships. Community health workers often act as mediators and coaches for people seeking medical and personal help. They could give good advice regarding hygiene, nutrition, protection of family members in case of HIV/AIDS and finding legal ways to earn one's living if they were trained to do so. Therefore they need to have a broader general knowledge. Since learning opportunities in the townships are scarce, a system for e-learning has to be created in order to overcome the lack of experience with computers or the Internet and to enable them to implement a network of expertise. The article describes how the best international resources on basic medical knowledge, HIV/AIDS as well as on basic economic and entrepreneurial skills were benchmarked to be integrated into an e-learning system. After tests with community health workers, researchers developed recommendations on building a self-sustaining system for learning, including a network of expertise and best practice sharing. The article explains the opportunities and challenges for community health workers, which could provide information for other parts of the world with similar preconditions of rural poverty.
Tan, Bowei; Abdelmalek, Cherif; O’Donnell, James E.; Toltaku, Thomas; Chaudhry, Rashid; Wang, Jen C.; Gotlieb, Vladimir
Patient: Male, 55 Final Diagnosis: Primary NK-T cell lymphoma • nasal type Symptoms: Fever • nasal bleeding • nasal mass • weight loss Medication: — Clinical Procedure: Chemotherapy×2 cycles • radiation therap Specialty: Oncology Objective: Rare disease Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is generally an aggressive and rare non-Hodgkin lymphoma. It is most common in East Asians, Native Americans, and South Americans, but is rarely reported in blacks. Case Report: A 55-year-old African American male born in Grenada presented with a left nostril mass with facial swelling and biopsy subsequently confirmed a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKTCL). Immunochemistry was positive for CD2, cytoplasmic CD3, CD7, CD 43, CD 56, granzyme B, and TIA-1. In situ hybridization was positive for Epstein-Barr virus encoded ribonucleic acid (EBERs). Bone marrow aspiration did not show lymphoma involvement. The patient had progressive neutropenia upon presentation, with further investigations showing hepatomegaly, hyperferritinemia, and hemophagocytosis in the bone marrow. We reached a diagnosis of hemophagocytic syndrome. He was treated with a high-dose combination chemotherapy and radiation therapy; the neutropenia improved significantly with steroids as treatment for immune activation in the setting of hemophagocytic syndrome. Conclusions: To the best of our knowledge, this is the only second report of extranodal NK/T-cell lymphoma, nasal type in a black patient, and it raises the awareness of early recognition of rare manifestations of NK/T-cell lymphoma such as hemophagocytic syndrome. PMID:28193996
Freiburghaus, F; Kaminsky, R; Nkunya, M H; Brun, R
Petroleum ether, dichloromethane, methanol and water extracts from 24 plants, belonging to 19 families, which are reported in the literature as traditional remedies for sleeping sickness (human African trypanosomiasis) were screened for in vitro activity against Trypanosoma brucei rhodesiense, as well as fro cytotoxicity for a human fibroblast cell-line (WI-38). The trypanocidal activity of the natural compounds berberine and harmane, both documented as being trypanocidal, was also evaluated. Promising trypanocidal activity with IC50 values below 10 micrograms/ml was found in 32 extracts of 13 plant species. The most active extracts with IC50 below 1 microgram/ml were derived from Annona senegalensis, Bussea occidentalis and Physalis angulata. The plant extracts showed a modest selectivity index, in contrast to commercially available trypanocides which have a more distinct selective toxicity against trypanosomes.
Mallewa, Macpherson; Wilmshurst, Jo M.
Infections of the central nervous system are a significant cause of neurologic dysfunction in resource-limited countries, especially in Africa. The prevalence is not known and is most likely underestimated because of the lack of access to accurate diagnostic screens. For children, the legacy of subsequent neurodisability, which affects those who survive, is a major cause of the burden of disease in Africa. Of the parasitic infections with unique effect in Africa, cerebral malaria, neurocysticercosis, human African trypanosomiasis, toxoplasmosis, and schistosomiasis are largely preventable conditions, which are rarely seen in resource-equipped settings. This article reviews the current understandings of these parasitic and other rarer infections, highlighting the specific challenges in relation to prevention, diagnosis, treatment, and the complications of coinfection. PMID:24655400
Paliwal, Sarvesh K.; Verma, Ankita Narayan; Paliwal, Shailendra
Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness. PMID:21886894
Pande, Saket; Keyzer, Michiel A; Arouna, Aminou; Sonneveld, Ben GJS
Background In West Africa, the Northern Sahelian zone and the coastal areas are densely populated but the Middle Belt in between is in general sparsely settled. Predictions of climate change foresee more frequent drought in the north and more frequent flooding in the coastal areas, while conditions in the Middle Belt will remain moderate. Consequently, the Middle Belt might become a major area for immigration but there may be constraining factors as well, particularly with respect to water availability. As a case study, the paper looks into the capacity of the Middle Belt zone of Benin, known as the Oueme River Basin (ORB), to reduce diarrhea prevalence. In Benin it links to the Millennium Development Goals on child mortality and environmental sustainability that are currently farthest from realization. However, diarrhea prevalence is only in part due to lack of availability of drinking water from a safe source. Social factors such as hygienic practices and poor sanitation are also at play. Furthermore, we consider these factors to possess the properties of a local public good that suffers from under provision and requires collective action, as individual actions to prevent illness are bound to fail as long as others free ride. Methods Combining data from the Demographic Health Survey with various spatial data sets for Benin, we apply mixed effect logit regression to arrive at a spatially explicit assessment of geographical and social determinants of diarrhea prevalence. Starting from an analysis of these factors separately at national level, we identify relevant proxies at household level, estimate a function with geo-referenced independent variables and apply it to evaluate the costs and impacts of improving access to good water in the basin. Results First, the study confirms the well established stylized fact on the causes of diarrhea that a household with access to clean water and with good hygienic practices will, irrespective of other conditions, not suffer
day test) system. Another approach to antimalarial chemotherapy is by using combinations of synergistically active compounds such as Fansidar...According to the World Health Organization, there is no adequate information on the prevalence of human African trypanosomiasis . The best estimates...report that 35 million people are exposed to the risk, and about 9,000 new cases are reported annually. African trypanosomiasis has a very high
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Discusses the traditional number systems and the origin of the number names used by several African peoples living south of the Sahara. Also included are limitations in African mathematical development, and possible topics for research. (RP)
Raymond, J T; Gerner, M
From December 1995 to July 1999, eight mammary gland tumors were diagnosed in eight adult captive female African hedgehogs (Atelerix albiventris). The tumors presented as single or multiple subcutaneous masses along the cranial or caudal abdomen that varied in size for each hedgehog. Histologically, seven of eight (88%) mammary gland tumors were malignant. Tumors were classified as solid (4 cases), tubular (2 cases), and papillary (2 cases). Seven tumors had infiltrated into the surrounding stroma and three tumors had histologic evidence of neoplastic vascular invasion. Three hedgehogs had concurrent neoplasms. These are believed to be the first reported cases of mammary gland tumors in African hedgehogs.
Rogers, D J
The human and animal trypanosomiases of Africa provide unique challenges to epidemiologists because of the spatial and temporal scales over which variation in transmission takes place. This chapter describes how our descriptions of the different components of transmission, from the parasites to the affected hosts, eventually developed to include geographical dimensions. It then briefly mentions two key analytical techniques used in the application of multi-temporal remotely sensed imagery to the interpretation of field data; temporal Fourier analysis for data reduction, and a variety of discriminant analytical techniques to describe the distribution and abundance of vectors and diseases. Satellite data may be used both for biological, process-based models and for statistical descriptions of vector populations and disease transmission. Examples are given of models for the tsetse Glossina morsitans in the Yankari Game Reserve, Nigeria, and in The Gambia. In both sites the satellite derived index of Land Surface Temperature (LST) is the best correlate of monthly mortality rates and is used to drive tsetse population models. The Gambia model is then supplemented with a disease transmission component; the mean infection rates of the vectors and of local cattle are satisfactorily described by the model, as are the seasonal variations of infection in the cattle. High and low spatial resolution satellite data have been used in a number of statistical studies of land cover types and tsetse habitats. In addition multi-temporal data may be related to both the incidence and prevalence of trypanosomiasis. Analysis of past and recent animal and human trypanosomiasis data from south-east Uganda supports the suggestion of the importance of cattle as a reservoir of the human disease in this area; mean infection prevalences in both human and animal hosts rise and fall in a similar fashion over the same range of increasing vegetation index values. Monthly sleeping sickness case data
From student and faculty exchanges to joint research projects, U.S. universities maintain a broad spectrum of collaborative relationships with African universities. It's unclear how many U.S. colleges and universities have partnerships with African universities. The African Studies Association, an organization of scholars, doesn't keep that kind…
Kamwendo, Gregory; Hlongwa, Nobuhle; Mkhize, Nhlanhla
After the demise of apartheid in South Africa in 1994, 11 languages (English, Afrikaans and 9 indigenous African languages) were given official status. In the higher education landscape, English remains the dominant language of scholarship. At the University of KwaZulu-Natal, English is the main medium of instruction but the institution's language…
In South Africa, there is a strong curriculum imperative for South African school science teachers to not only involve learners in practical inquiry activities but also to support students in making a connection between the construction of substantive scientific knowledge to these activities. The research reported in this article investigated the…
Gyapong, Samuel K.; Smith, Thomas
In an effort to assist a newly appointed Public Relations Officer to determine the most effective way to promote the institution to college-bound Generation Y African-Americans we offered to conduct a survey research of our current students. The results were very revealing and have been used successfully to increase enrollment to historically high…
Globalization and privatization have begun to destabilize the patterns of university professional work and campus community. African American Women Administrators battle the unique challenges of racial and gender discrimination as well as the intersection of these issues. AAWAs face feelings of isolation and lack of trust, and struggles over power…
This article describes a small scale ethnographically oriented research study seeking to contribute to understanding student academic literacy practices in a South African vocational, web design and development course. In this course digital multimodal assessments are the main means whereby students demonstrate their learning. The findings of the…
Naar-King, Sylvie; Ellis, Deborah; Kolmodin, Karen; Cunningham, Phillippe; Secord, Elizabeth
African-American adolescents have the highest rates of asthma morbidity and mortality, yet there are few successful behavioral interventions to improve illness management for this group. Mental health providers have an opportunity to expand their services and impact by targeting adolescents with poor asthma management. We describe the adaptation…
Ambrósio, Susana; Marques, João Filipe; Santos, Lucília; Doutor, Catarina
We present a study to comprehend if the support given by higher education institution (HEI) to international students coming from the Portuguese-Speaking African Countries meets their academic and social hindrances. Our starting point was a set of semi-structured interviews focused on the perspectives of these students, their Professors and Course…
Martin, Robin L.
Leadership remains an important topic across various disciples. The continuous demonstration of effective leadership and its impact on institutions and society fuels the inquiry into the various ways, behaviors, traits, and situations in which leaders and leadership are successful (Kezar & Lester, 2011). As more African Americans advance in…
Milani, Lorenzo; Lehmann, Jérémie; Naydenov, Kalin V.; Saalmann, Kerstin; Kinnaird, Judith A.; Daly, J. Stephen; Frei, Dirk; Lobo-Guerrero Sanz, Alberto
The Pan-African Hook Batholith formed during the assembly of the Gondwana supercontinent as a result of syn-collisional stage interaction between the Congo and Kalahari Cratons. The bimodal magmatism (mafic to predominantly felsic) is characterized by both an alkali-calcic and an alkalic suite, with typical A-type, metaluminous, high Fe/Mg and K/Na geochemical signature. Occasionally, sodic granitoids have been documented. Compositions were driven to more differentiated products by fractional crystallization, while Sr-Nd isotopes exclude crustal assimilation during crystallization. Recent new U-Pb age data constrain most of the felsic magmatism between 550 and 540 Ma. Scattered outcrops of gabbroic rocks, both tholeiitic and alkaline, testify to periodic input of mantle material, and, in some cases, to interaction with metasomatizing fluids. Crystallization ages on mafic rocks span from 570 to 520 Ma, thus indicating that they were contemporaneous with the major granitic intrusion, which was the result of a number of successive felsic batches, eventually forming a coalescing batholith. Highly radiogenic Pb isotopic values attest to the radiogenic character of the rocks. Such an anomalous signature was acquired during, or soon after, magma emplacement, perhaps as result of metasomatizing fluids. Enrichment in Th-U of large portions of the crust along this part of the margin of the Congo Craton is suggested. Geochemical and isotopic evidence support the interaction between mantle components and portions of the deep crust at pressure of < 10 kbar, while decompression melting of rising asthenospheric mantle ponding at the base of the crust heated, and ultimately melted, crustal material. An additional and crucial contribution to the crustal melting was likely provided by internal radiogenic heat production of the thickened crust, and is in agreement with the high radioactivity of the pluton. A tectono-thermal model, implying crustal accretion accompanied by slab
Falade, Catherine O.; Ajayi, IkeOluwapo O.; Nsungwa-Sabiiti, Jesca; Siribié, Mohamadou; Diarra, Amidou; Sermé, Luc; Afonne, Chinenye; Yusuf, Oyindamola B.; Gansane, Zakaria; Jegede, Ayodele S.; Singlovic, Jan; Gomes, Melba
Background. The World Health Organization recommends that malaria treatment be based on demonstration of the infecting Plasmodium parasite specie. Malaria rapid diagnostic tests (RDTs) are recommended at community points of care because they are accurate and rapid. We report on parasitological results in a malaria study in selected rural communities in 3 African countries. Methods. In Nigeria, community health workers (CHWs) performed RDTs (SD-Bioline) and thick blood smears on all children suspected to have malaria. Malaria RDT-positive children able to swallow received artemisinin-based combination therapy (Coartem). In all countries, children unable to take oral drugs received prereferral rectal artesunate irrespective of RDT result and were referred to the nearest health facility. Thick blood smears and RDTs were usually taken at hospital admission. In Nigeria and Burkina Faso, RDT cassettes and blood smears were re-read by an experienced investigator at study end. Results. Trained CHWs enrolled 2148 children in Nigeria. Complete parasitological data of 1860 (86.6%) enrollees were analyzed. The mean age of enrollees was 30.4 ± 15.7 months. The prevalence of malaria parasitemia in the study population was 77.8% (1447/1860), 77.6% (1439/1855), and 54.1% (862/1593) by RDT performed by CHWs vs an expert clinical research assistant vs microscopy (gold standard), respectively. Geometric mean parasite density was 6946/µL (range, 40–436 450/µL). There were 49 cases of RDT false-negative results with a parasite density range of 40–54 059/µL. False-negative RDT results with high parasitemia could be due to non-falciparum infection or result from a prozone effect. Sensitivity and specificity of SD-Bioline RDT results as read by CHWs were 94.3% and 41.6%, respectively, while the negative and positive predictive values were 86.1% and 65.6%, respectively. The level of agreement in RDT reading by the CHWs and experienced research staff was 86.04% and κ
Radomski, M W; Buguet, A; Doua, F; Bogui, P; Tapie, P
Human African trypanosomiasis (sleeping sickness) is a unique disease model of disrupted circadian rhythms in the sleep-wake cycle and cortisol and prolactin secretion. This study examined the temporal relationship between growth hormone (GH) secretion and the sleep-wake cycle in 8 infected African patients and 6 healthy indigenous African subjects. Twenty-four-hour sleep patterns were recorded by polysomnography and hourly blood samples analyzed for plasma GH. No relationships between the mean normalized plasma GH levels (Z scores) and the sleep stages (wakefulness, sleep stages 1 and 2 ('light' sleep), slow-wave sleep (stages 3 and 4, SWS), and rapid eye movement (REM) sleep) were found in the patients or healthy subjects. However, when the time of sampling of the plasma GH concentrations was lagged by 16 min with respect to the occurrence of the various sleep stages, significant correlations were found between plasma GH concentrations and SWS in both healthy subjects and patients. Thus, the association between SWS and GH secretion persisted even in the presence of disrupted circadian rhythms, further supporting the concept that sleep and the stimulation of GH secretion are outputs of a common mechanism.
Munang'andu, Hetron Mweemba; Siamudaala, Victor; Munyeme, Musso; Nalubamba, King Shimumbo
Trypanosomiasis has been endemic in wildlife in Zambia for more than a century. The disease has been associated with neurological disorders in humans. Current conservation strategies by the Zambian government of turning all game reserves into state-protected National Parks (NPs) and game management areas (GMAs) have led to the expansion of the wildlife and tsetse population in the Luangwa and Zambezi valley ecosystem. This ecological niche lies in the common tsetse fly belt that harbors the highest tsetse population density in Southern Africa. Ecological factors such as climate, vegetation and rainfall found in this niche allow for a favorable interplay between wild reservoir hosts and vector tsetse flies. These ecological factors that influence the survival of a wide range of wildlife species provide adequate habitat for tsetse flies thereby supporting the coexistence of disease reservoir hosts and vector tsetse flies leading to prolonged persistence of trypanosomiasis in the area. On the other hand, increase in anthropogenic activities poses a significant threat of reducing the tsetse and wildlife habitat in the area. Herein, we demonstrate that while conservation of wildlife and biodiversity is an important preservation strategy of natural resources, it could serve as a long-term reservoir of wildlife trypanosomiasis.
as a regional and continental power its position likely influenced opens decisions. The thesis then concludes with a summary of findings, and a...America: Foreign Policy, Cooperation and Conflict (M.A. Thesis , University of Kansas, International Studies, 2004). 32 assistance, and in the face of...Oxford: Oxford University Press for the International Institute for Strategic Studies, 2003), 27. 40 The South African Defense Forces (SADF
Strachan, Samantha L.
The underachievement of African American students in science has been a persistent problem in science education. The achievement patterns of African American students indicate that researchers must take a closer look at the types of practices that are being used to meet these students' needs in science classrooms. Determining why science teachers decide to employ certain practices in their classrooms begins with a careful examination of teachers' beliefs as well as their instructional approaches. The purpose of this study was to explore four urban high school science teachers' beliefs about their African American students' learning needs and to investigate how these teachers go about addressing students' needs in science classrooms. This research study also explored the extent to which teachers' practices aligned with the nine dimensions of an established cultural instructional theory, namely the Black Cultural Ethos. Qualitative research methods were employed to gather data from the four teachers. Artifact data were collected from the teachers and they were interviewed and observed. Believing that their students had academic-related needs as well as needs tied to their learning preferences, the four science teachers employed a variety of instructional strategies to meet their students where they were in learning. Overall, the instructional strategies that the teachers employed to meet their students' needs aligned with five of the nine tenets of the Black Cultural Ethos theory.
Nyblade, Andrew A.; Robinson, Scott W.
Maps of residual bathymetry in the ocean basins around the African continent reveal a broad bathymetric swell in the southeastern Atlantic Ocean with an amplitude of about 500 m. We propose that this region of anomalously shallow bathymetry, together with the contiguous eastern and southern African plateaus, form a superswell which we refer to as the African superswell. The origin of the African superswell is uncertain. However, rifting and volcanism in eastern Africa, as well as heat flow measurements in southern Africa and the southeastern Atlantic Ocean, suggest that the superswell may be attributed, at least in part, to heating of the lithosphere.
Allen, Keisha McIntosh; Jackson, Iesha; Knight, Michelle G.
This study presents findings from a case study of 18 second- and 1.5-generation West African immigrants. We draw upon notions of elusive culture and indigenous knowledges to highlight participants' complex cultural identities and respond to anti-immigration discourses through positioning West African immigrant students as assets in American…
Dickens, Manuel Dewayne
The purpose of this qualitative case study that consists of six African American male participants is to examine, describe, and analyze African American male persistence factors at a community college in the midwest of the United States. The study uses qualitative content analysis as a research method that provides a systematic and objective means…
African-American Inst., New York, NY. School Services Div.
An interdisciplinary focus on the teaching of African geography is presented in this module, arranged by three major topics. Topic I stresses the African view that water is the sustainer of life, presents a case study of the Nile River, and discusses the significance of rivers as natural boundaries that delineate political units. Topic II gives…
Clindamycin is a bacteriostatic lincosamide antibiotic with a broad spectrum. Side effects include nausea, vomiting, diarrhea, and metallic taste; however, hepatotoxicity is rare. The incidence is unknown. It is characterized by increases in aspartate and alanine transaminases. There may be no symptoms and the treatment is to stop the administration of clindamycin. We have described a 62-year-old African American female medicated with acetaminophen and clindamycin who had initially presented to the dental clinic for the evaluation of gum pain following tooth extraction. She had significantly increased levels of liver transaminases, which trended downwards on quitting the medication. PMID:27462474
Chritz, Kendra L.; Marshall, Fiona B.; Zagal, M. Esperanza; Kirera, Francis; Cerling, Thure E.
Specialized pastoralism developed ∼3 kya among Pastoral Neolithic Elmenteitan herders in eastern Africa. During this time, a mosaic of hunters and herders using diverse economic strategies flourished in southern Kenya. It has been argued that the risk for trypanosomiasis (sleeping sickness), carried by tsetse flies in bushy environments, had a significant influence on pastoral diversification and migration out of eastern Africa toward southern Africa ∼2 kya. Elmenteitan levels at Gogo Falls (ca. 1.9–1.6 kya) preserve a unique faunal record, including wild mammalian herbivores, domestic cattle and caprines, fish, and birds. It has been suggested that a bushy/woodland habitat that harbored tsetse fly constrained production of domestic herds and resulted in subsistence diversification. Stable isotope analysis of herbivore tooth enamel (n = 86) from this site reveals, instead, extensive C4 grazing by both domesticates and the majority of wild herbivores. Integrated with other ecological proxies (pollen and leaf wax biomarkers), these data imply an abundance of C4 grasses in the Lake Victoria basin at this time, and thus little risk for tsetse-related barriers to specialized pastoralism. These data provide empirical evidence for the existence of a grassy corridor through which small groups of herders could have passed to reach southern Africa. PMID:25775535
Eloy, Luciano José; Lucheis, Simone Baldini
Introduction. American trypanosomiasis, also known as Chagas disease, is a zoonosis caused by Trypanosoma cruzi (T. cruzi). Dogs and cats participate actively in this parasite's transmission cycle. This study aimed at evaluating the occurrence of T. cruzi in dogs and cats from Botucatu, SP, Brazil, as well as at evaluating the technique of hemoculture in LIT (liver infusion tryptose) medium by polymerase chain reaction (PCR). Methods. Blood samples were collected from 50 dogs and 50 cats in Botucatu-SP, Brazil. For hemoculture, the samples were inoculated in LIT medium, and readings were performed for four months. Upon completion of such period, all the hemocultures were processed for parasitic DNA extraction. The PCR reactions were performed by using primers TCZ1/TCZ2. Results. Ten dogs and ten cats (20%) were positive to PCR, and four dogs and three cats (7%) were positive to hemoculture. Only in a one cat sample (1%) there was confirmation of positive hemoculture by PCR for T. cruzi. Conclusions. Results showed that PCR was a suitable tool for the confirmation of the parasite detection in hemoculture samples, and that dogs and cats from Botucatu, SP, Brazil, are maintaining the role of household reservoirs of T. cruzi, which reinforces the need for constant epidemiologic surveillance for this zoonosis. PMID:23738124
Alingu, Richard A; Muhanguzi, Dennis; MacLeod, Ewan; Waiswa, Charles; Fyfe, Jenna
A cross-sectional study was conducted in Mbarara district, south-western Uganda in May 2012 to determine the burden of African animal trypanosomosis (AAT) in the semi-intensive dairy production systems where pyrethroid acaricides are frequently used in the control of tick-borne diseases (TBDs). A total of 295 cattle blood samples were taken and analysed using a single pair of primers previously designed to amplify internal transcribed spacer (ITS1) of trypanosome ribosomal deoxyribonucleic acid (rDNA). A structured questionnaire was administered to 55 participating livestock farmers to generate data on acaricide and trypanocidal drug usage. The overall prevalence of trypanosome species was 2.4% (95% CI; 1.0% - 4.8%); Trypanosoma vivax was the most predominant species (2.0%; 95% CI; 0.7% - 4.4%). A single mixed infection of T. vivax and Trypanosoma brucei s.l. was detected. All the participating farmers used acaricides for tsetse and TBD control; 89.1% of the acaricides used were pyrethroids. About half of the farmers used trypanocidal drugs, mainly diminazene formulations (Berenil®). Low prevalence of trypanosomes in examined samples is most likely related to the frequent use of pyrethroid insecticides, trypanocides and restricted grazing (paddocking and tethering). These rigorous management practices are geared towards optimising production of exotic dairy breeds kept in this region that are highly susceptible to TBDs and AAT.
Dje, N N; Miezan, T W; N'guessan, P; Brika, P; Doua, F; Boa, F
Human African Trypanosomosis (HAT, or sleeping sickness) caused by Trypanosoma brucei gambiense develops chronically in Côte d'Ivoire. From 1993 to 2000, a total of 1616 patients were taken in charge in the three treatment centres of the country, which means an average of 202 patients a year. The patients came from two main areas in the Centre West of the country in the Marahoué 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-Ayamé), patients are still struck by the disease, although these foci are less active. The remaining foci seem to be controlled, although no active survey has been carried out. The areas where the greatest number of patients were recorded are the ones where rental crops are located (cocoa and coffee mainly) and where rural activities tend to bring humans and tsetse flies in contact. In this study, are figured the number of treated patients, the endemic and risk areas. It will help to design control strategies and decision makers to know where priority control programs should be implemented.
Komp, K. U.; Haub, C.
After four decades of space borne remote sensing, the unmapped white patches have mostly disappeared. Those basic information give the foundations to the observation of changes and even the introduction of monitoring programmes for a various number of features in the natural and human landscape of our planet. Recent indicators for climatic change together with worrisome alterations in regional food production versus the constantly increase of human population demand the design and implementation of reliable land management tools which will serve the food security as well as the sustainable use of resources of the ecosystem in its respective regional context. The positive responses and convincing results of ESA service elements in the efforts towards food security in several African countries have been the basis for the transfer of the methods into another region, the Western Siberian corn-belt. The large extends of cropping schemes in West Siberia demand advanced remote sensing methods to be applied in order to compare the impacts of climatic change not only on the agricultural production but also on risks for the ecosystem. A multi scale approach of remote sensing methods is introduced in analogy to the African activities. An adopted monitoring concept is developed using a nearly daily product of medium resolution for wide areas, high resolution sensors for stratified sample areas and in-situ observations. Beyond methodological research, the ability of remote sensing is contributing to operational solutions that can ensure the nutritional and ecological future of our planet.
Bell, Edward Earl
The purpose of this study was to assess the socialization skills, self-esteem, and academic readiness of African American males in a school environment. Discussions with students and the School Perceptions Questionnaire provided data for this investigation. The intended targets for this investigation were African American students; however, there…
Clarke, John Henrik
Africans who were brought across the Atlantic as slaves never fully adjusted to slavery or accepted its inevitability. Resistance began on board the slave ships, where many jumped overboard or committed suicide. African slaves in South America led the first revolts against tyranny in the New World. The first slave revolt in the Caribbean occurred…
Bell, Edward E.
Background: Schools across America spend money, invest in programs, and sponsor workshops, offer teacher incentives, raise accountability standards, and even evoke the name of Obama in efforts to raise the academic achievement of African American males. Incarceration and college retention rates point to a dismal plight for many African American…
This collection for children tells the stories of 16 African Americans who helped make America what it is today. African Americans can take pride in the heritage of these contributors to society. Biographies are given for the following: (1) Sojourner Truth, preacher and abolitionist; (2) Frederick Douglass, abolitionist; (3) Harriet Tubman, leader…
Art is a good place to learn about our multicultural planet, and African masks are prized throughout the world as powerfully expressive artistic images. Unfortunately, multicultural education, especially for young children, can perpetuate stereotypes. Masks taken out of context lose their meaning and the term "African masks" suggests that there is…
Rowlett, Joel Everett
This case study examined the beliefs of African American males on the psychosocial and pedagogical factors contributing to the underrepresentation of African American males in advanced high school math courses. Six 11th grade African American male juniors from a large, comprehensive, Southeastern high school served as individual cases. Within- and…
Berge, Benoit; Chevrier, Céline; Blanc, Alain; Rehailia, Mohamed; Buguet, Alain; Bourdon, Lionel
Periodogram techniques on detrended data were used to determine the incidence of Trypanosoma brucei brucei infection on the distribution of the core temperature of rats and the expression of temperature rhythms. In such an animal model, sudden episodic hypothermic bouts were described. These episodes of hypothermia are used here as temporal marks for the purpose of performing punctual comparisons on temperature organization. The experiment was conducted on 10 infected and 3 control Sprague-Dawley rats reared under a 24 h light-dark cycle. Core temperature was recorded continuously throughout the experiment, until the animals' death. Temperature distributions, analyzed longitudinally across the full duration of the experiment, exhibited a progressive shift from a bimodal to unimodal pattern, suggesting a weakening of the day/night core temperature differences. After hypothermic events, the robustness of the circadian rhythm substantially weakened, also affecting the ultradian components. The ultradian periods were reduced, suggesting fragmentation of temperature generation. Moreover, differences between daytime and nighttime ultradian patterns decreased during illness, confirming the weakening of the circadian component. The results of the experiments show that both core temperature distribution and temperature rhythm were disrupted during the infection. These disruptions worsened after each episode of hypothermia, suggesting an alteration of the temperature regulatory system.
Smith, D R; Taylor, O R; Brown, W M
Non-indigenous African honey bees have invaded most of South and Central America in just over 30 years. The genetic composition of this population and the means by which it rapidly colonizes new territory remain controversial. In particular, it has been unclear whether this 'Africanized' population has resulted from interbreeding between African and domestic European bees, or is an essentially pure African population. Also, it has not been known whether this population expanded primarily by female or by male migration. Restriction site mapping of 62 mitochondrial DNAs of African bees from Brazil, Venezuela and Mexico reveals that 97% were of African (Apis mellifera scutellata) type. Although neotropical European apiary populations are rapidly Africanized by mating with neotropical African males, there is little reciprocal gene flow to the neotropical African population through European females. These are the first genetic data to indicate that the neotropical African population could be expanding its range by female migration.
Shuaibu, M N; Kanbara, H; Yanagi, T; Ichinose, A; Ameh, D A; Bonire, J J; Nok, A J
Diorganotins (R2SnX2) are compounds with a wide variety of biological properties. In an attempt to follow the morphological events and to characterize the toxic effects of diorganotins on in vitro cultured African Trypanosoma spp., the ultrastructural alterations induced on the parasites by dibutyltins (Bu2SnX2) were followed. The data obtained indicate that these compounds induced irreparable damage to the in vitro cultured bloodstream forms of the parasites. Transmission and scanning electron microscopy allowed observations on the perturbation of the kinetoplast, extensive cytoplasmic swellings, disconfiguration around the flagellar pocket and membrane disintegration. Fluorescence microscopy with 4,6-diamidine-2-phenylindole stain was also used to visualize the survival or degeneration of kDNA. Understanding the collateral cellular toxic effect of these compounds on the parasites may shed light on the possible mechanism by which they kill trypanosomes. Agarose gel electrophoresis resolution of isolated kDNAs revealed no fragmentation by these compounds following in vitro incubation at 37 degrees C. However, fragmentation was observed from the gel electrophoresis of kDNA isolated from in vitro cultured Bu2SnX2-exposed parasites. Transmission electron microscopy of the kDNAs revealed the same pattern as observed with gel electrophoresis. These results provide evidence for the possible involvement of the Bu2Sn moiety in the in vivo-induced fragmentation of trypanosomal kDNA and consequent trypanolysis. This observation also underlies the relevance of organometallics in the therapy of African trypanosomiasis.
de Jong, Bouke C; Adetifa, Ifedayo; Walther, Brigitte; Hill, Philip C; Antonio, Martin; Ota, Martin; Adegbola, Richard A
Mycobacterium africanum (MAF) is a common cause of human pulmonary tuberculosis in West Africa. We previously described phenotypic differences between MAF and Mycobacterium tuberculosis (MTB) among 290 patients. In the present analysis, we compared 692 tuberculosis patients infected with the two most common lineages within the (MTB) complex found in the Gambia, namely MAF West African type 2 (39% prevalence) and Euro-American MTB (55% prevalence). We identified additional phenotypic differences between infections with these two organisms. MAF patients were more likely to be older and HIV infected. In addition, they had worse disease on chest X-ray, despite complaining of cough for an equal duration, and were more likely severely malnourished. In this cohort, the prevalence of MAF did not change significantly over a 7-year period.
Cazers, Gunars; Curtner-Smith, Matthew
Purpose: The purpose was to reconstruct the historical and legendary contribution of one exemplary African American physical education teacher educator who lived and worked in the Deep South prior to and immediately following the 1954 Brown v. Board of Education court case. The following questions guided data collection and analysis: To what…
a.o & % Nb...I- V. THE CHEMOTHERAPY OF EXPERIMENTALLY INDUCED DRUG- r RESISTANT AFRICAN TRYPANOSOMIASIS (I. JLEJNE) IN MICE. A. Introduction 31 B...Methods 31 C. Results 33 D. Summary of compounds tested (Table VII). 35 VI. THE CHEMOTHERAPY OF EXPERIMENTALLY INDUCED AMERICAN TRYPANOSOMIASIS (_T...rhodesiense Plasmodium berghei Prophylactic African trypanosomiasis P. yoelii Repository American trypanosomiasis Drug-sensitive Suppressive
... accounted for 83.8% of Caucasian elderly suicides. • Firearms were the predominant method of suicide among African ... per 100,000 annually. Source: Centers for Disease Control and Prevention. National Vital Statistics System. Mortality Data. ...
... and Management System Report to Congress Knowledge Center Capacity Building Information Services Events Calendar Resource Guide Justice ... Workforce Diversity Grants Youth Program Grants Other Grants Planning and Evaluation Grantee Best Practices Black/African American ...
A phenomenological case study concerning science teacher educators' beliefs and teaching practices about culturally relevant pedagogy and preparing K-12 science teachers to engage African American students in K-12 science
Underwood, Janice Bell
Due to the rising diversity in today's schools, science teacher educators (STEs) suggest that K-12 teachers must be uniquely prepared to engage these students in science classrooms. Yet, in light of the increasing white-black science achievement gap, it is unclear how STEs prepare preservice teachers to engage diverse students, and African Americans in particular. Therefore, the purpose of this study was to find out how STEs prepare preservice teachers to engage African American students in K-12 science. Thus, using the culturally relevant pedagogy (CRP) framework, this phenomenological case study explored beliefs about culturally relevant science teaching and the influence of reported beliefs and experiences related to race on STEs' teaching practices. In the first phase, STE's in a mid-Atlantic state were invited to participate in an electronic survey. In the second phase, four participants, who were identified as exemplars, were selected from the survey to participate in three semi-structured interviews. The data revealed that STEs were more familiar with culturally responsive pedagogy (CResP) in the context of their post-secondary classrooms as opposed to CRP. Further, most of the participants in part one and two described modeling conventional ways they prepare their preservice teachers to engage K-12 students, who represent all types of diversity, without singling out any specific race. Lastly, many of the STEs' in this study reported formative experiences related to race and beliefs in various manifestations of racism have impacted their teaching beliefs and practices. The findings of this study suggest STEs do not have a genuine understanding of the differences between CRP and CResP and by in large embrace CResP principles. Secondly, in regards to preparing preservice teachers to engage African American students in science, the participants in this study seemed to articulate the need for ideological change, but were unable to demonstrate pedagogical changes
DeSantis, Carol; Naishadham, Deepa; Jemal, Ahmedin
In this article, the American Cancer Society estimates the number of new cancer cases and deaths for African Americans and compiles the most recent data on cancer incidence, mortality, survival, and screening prevalence based upon incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. It is estimated that 176,620 new cases of cancer and 64,880 deaths will occur among African Americans in 2013. From 2000 to 2009, the overall cancer death rate among males declined faster among African Americans than whites (2.4% vs 1.7% per year), but among females, the rate of decline was similar (1.5% vs 1.4% per year, respectively). The decrease in cancer death rates among African American males was the largest of any racial or ethnic group. The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of nearly 200,000 deaths from cancer among African Americans. Five-year relative survival is lower for African Americans than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Overall, progress in reducing cancer death rates has been made, although more can and should be done to accelerate this progress through ensuring equitable access to cancer prevention, early detection, and state-of-the-art treatments.
The level of convergence between a rodent, the South American lowland paca Cuniculus paca, and a ruminant, the African water chevrotain Hyemoschus aquaticus, is analysed using 231 characteristics belonging to different biological sectors. A convergence index is established based on the degree of rarity of each characteristic in each species compared to other members of its zoological group. Although the divergent characteristics are as numerous as the convergent ones, the two species are globally similar. Convergent characteristics occur in all biological categories, but their rate varies a great deal among them. From internal anatomy and osteology, through behaviour and ecology to the external appearance of the body, convergent characteristics are all the more frequent since the biological category is directly implicated in the adaptation of animals to their external environment (lowland rainforest). However, only the individuals' characteristics are concerned and not those of their population or social organisation. This could be due to differences between the communities of terrestrial mammals to which they belong.
Eiser, Arnold R; Ellis, Glenn
Achieving cultural competence in the care of a patient who is a member of an ethnic or racial minority is a multifaceted project involving specific cultural knowledge as well as more general skills and attitude adjustments to advance cross-cultural communication in the clinical encounter. Using the important example of the African American patient, the authors examine relevant historical and cultural information as it relates to providing culturally competent health care. The authors identify key influences, including the legacy of slavery, Jim Crow discrimination, the Tuskegee syphilis study, religion's interaction with health care, the use of home remedies, distrust, racial concordance and discordance, and health literacy. The authors propose that the awareness of specific information pertaining to ethnicity and race enhances cross-cultural communication and ways to improve the cultural competence of physicians and other health care providers by providing a historical and social context for illness in another culture. Cultural education, modular in nature, can be geared to the specific populations served by groups of physicians and provider organizations. Educational methods should include both information about relevant social group history as well as some experiential component to emotively communicate particular cultural needs. The authors describe particular techniques that help bridge the cross-cultural clinical communication gaps that are created by patients' mistrust, lack of cultural understanding, differing paradigms for illness, and health illiteracy.
Reindl, Andrzej R; Falkowska, Lucyna
The present study estimated hexabromocyclododecane (HBCD) as a sum of three main isomers (α, β, and γ) and tetrabromobisphenol A (TBBPA) in African penguins (Spheniscus demersus) from Gdansk Zoo and in their sole food, Baltic herring (Clupea harengus), from Gdansk Bay. The average concentration of HBCD in whole herring was 22.0 ± 9.9 ng/g lw, whereas TBBPA was approximately 10-fold lower (2.3 ± 1.3 ng/g lw). Brominated flame retardants (BFRs) were also found in muscle and liver of herring. The estimated daily dietary exposure of the penguins to HBCD was 252.9 ± 113.7 ng, whereas for TBBPA it was 26.3 ± 14.9 ng. The ability of BFRs to accumulate in the liver, muscles, fatty tissue, and brain of penguin was confirmed. The highest concentrations of HBCD (326.9 ng·g(-1) lw) and TBBPA (14.8 ng·g(-1) lw) were found in the brain of an adult penguin. The strongest accumulation factor for BFRs was also established for brain tissue, but it showed stronger magnification in muscle than in liver. HBCD and TBBPA were found in penguin guano and eggs, thus showing effective removal from the birds' systems. BFRs content in yolk was approximately ten times greater than in albumen indicating the lipophilic character of these compounds.
Background Both treatment and prevention strategies are recommended by the World Health Organization for the control of malaria during pregnancy in tropical areas. The aim of this study was to assess use of a rapid diagnostic test for prompt management of malaria in pregnancy in Bangui, Central African Republic. Methods A cohort of 76 pregnant women was screened systematically for malaria with ParacheckPf® at each antenatal visit. The usefulness of the method was analysed by comparing the number of malaria episodes requiring treatment in the cohort with the number of prescriptions received by another group of pregnant women followed-up in routine antenatal care. Results In the cohort group, the proportion of positive ParacheckPf® episodes during antenatal clinics visits was 13.8%, while episodes of antimalarial prescriptions in the group which was followed-up routinely by antenatal personnel was estimated at 26.3%. Hence, the relative risk of the cohort for being prescribed an antimalarial drug was 0.53. Therefore, the attributable fraction of presumptive treatment avoided by systematic screening with ParacheckPf® was 47%. Conclusions Use of a rapid diagnostic test is useful, affordable and easy for adequate treatment of malaria in pregnant women. More powerful studies of the usefulness of introducing the test into antenatal care are needed in all heath centres in the country and in other tropical areas. PMID:22734602
Ley, A C; Hardy, O J
AFLP markers are often used to study patterns of population genetic variation and gene flow because they offer a good coverage of the nuclear genome, but the reliability of AFLP scoring is critical. To assess interspecific gene flow in two African rainforest liana species (Haumania danckelmaniana, H. liebrechtsiana) where previous evidence of chloroplast captures questioned the importance of hybridization and species boundaries, we developed new AFLP markers and a novel approach to select reliable bands from their degree of reproducibility. The latter is based on the estimation of the broad-sense heritability of AFLP phenotypes, an improvement over classical scoring error rates, which showed that the polymorphism of most AFLP bands was affected by a substantial nongenetic component. Therefore, using a quantitative genetics framework, we also modified an existing estimator of pairwise kinship coefficient between individuals correcting for the limited heritability of markers. Bayesian clustering confirms the recognition of the two Haumania species. Nevertheless, the decay of the relatedness between individuals of distinct species with geographic distance demonstrates that hybridization affects the nuclear genome. In conclusion, although we showed that AFLP markers might be substantially affected by nongenetic factors, their analysis using the new methods developed considerably advanced our understanding of the pattern of gene flow in our model species.
Ley, A C; Hardy, O J
Gene flow within and between species is a fundamental process shaping the evolutionary history of taxa. However, the extent of hybridization and reinforcement is little documented in the tropics. Here we explore the pattern of gene flow between three sister species from the herbaceous genus Marantochloa (Marantaceae), sympatrically distributed in the understorey of the African rainforest, using data from the chloroplast and nuclear genomes (DNA sequences and AFLP). We found highly contrasting patterns: while there was no evidence of gene flow between M. congensis and M. monophylla, species identity between M. monophylla and M. incertifolia was maintained despite considerable gene flow. We hypothesize that M. incertifolia originated from an ancient hybridization event between M. congensis and M. monophylla, considering the current absence of hybridization between the two assumed parent species, the rare presence of shared haplotypes between all three species and the high percentage of haplotypes shared by M. incertifolia with each of the two parent species. This example is contrasted with two parapatrically distributed species from the same family in the genus Haumania forming a hybrid zone restricted to the area of overlap. This work illustrates the diversity of speciation/introgression patterns that can potentially occur in the flora of tropical Africa.
Goff, P.; Hulse, A.; Harder, H. R.; Pierce, L. A.; Rizzo, D.; Hanley, J.; Orantes, L.; Stevens, L.; Justi, S.; Monroy, C.
A computational simulation has been designed as an investigative case study by high school students to introduce system dynamics modeling into high school curriculum. This case study approach leads users through the forensics necessary to diagnose an unknown disease in a Central American village. This disease, Chagas, is endemic to 21 Latin American countries. The CDC estimates that of the 110 million people living in areas with the disease, 8 million are infected, with as many as 300,000 US cases. Chagas is caused by the protozoan parasite, Trypanosoma cruzi, and is spread via blood feeding insect (vectors), that feed on vertebrates and live in crevasses in the walls and roofs of adobe homes. One-third of the infected people will develop chronic Chagas who are asymptomatic for years before their heart or GI tract become enlarged resulting in death. The case study has three parts. Students play the role of WHO field investigators and work collaboratively to: 1) use genetics to identify the host(s) and vector of the disease 2) use a STELLA™ SIR (Susceptible, Infected, Recovered) system dynamics model to study Chagas at the village scale and 3) develop management strategies. The simulations identify mitigation strategies known as Ecohealth Interventions (e.g., home improvements using local materials) to help stakeholders test and compare multiple optima. High school students collaborated with researchers from the University of Vermont, Loyola University and Universidad de San Carlos, Guatemala, working in labs, interviewing researchers, and incorporating mulitple field data as part of a NSF-funded multiyear grant. The model displays stable equilibria of hosts, vectors, and disease-states. Sensitivity analyses show measures of household condition and presence of vertebrates were significant leverage points, supporting other findings by the University research team. The village-scale model explores multiple solutions to disease mitigation for the purpose of producing
Odongo, Steven; Delespaux, Vincent; Ngotho, Maina; Bekkele, Serkalem Mindaye; Magez, Stefan
We compared the nested internal transcribed spacer (ITS) PCR and the 18S PCR-RFLP (restriction-fragment length polymorphism) pan-trypanosome assays in a cross-sectional survey of bovine trypanosomiasis in 358 cattle in Kwale County, Kenya. The prevalence of trypanosomiasis as determined by the nested ITS PCR was 19.6% (70/358) and by 18S PCR-RFLP was 16.8% (60/358). Of the pathogenic trypanosomes detected, the prevalence of Trypanosoma congolense and Trypanosoma vivax was greater than that of Trypanosoma simiae The nested ITS PCR detected 83 parasite events, whereas the 18S PCR-RFLP detected 64; however, overall frequencies of infections and the parasite events detected did not differ between the assays (χ(2) = 0.8, df = 1, p > 0.05 and χ(2) = 2.5, df = 1, p > 0.05, respectively). The kappa statistic (0.8) showed good agreement between the tests. The nested ITS PCR and the 18S PCR-RFLP had comparable sensitivity, although the nested ITS PCR was better at detecting mixed infections (χ(2) = 5.4, df = 1, p < 0.05).
Yoo, Thomas W; Mlikotic, Anton; Cornford, Marcia E; Beck, C Keith
We report a case of concurrent cerebral infection with Trypanosoma cruzi and Toxoplasma gondii in a patient with acquired immunodeficiency syndrome (AIDS). A 22-year-old El Salvadoran man initially improved during receipt of antitoxoplasmosis therapy, but he had rapidly progressive hemiplegia. Magnetic resonance imaging showed an abnormal finding in the left internal capsule, and cytological analysis of cerebrospinal fluid revealed T. cruzi trypomastigotes. Despite prompt therapy with nifurtimox, the patient's mental status declined, and he died of nosocomial complications. Although infrequent, T. cruzi infection should be considered in the differential diagnosis of brain lesions in patients with AIDS from regions of endemicity.
Instruments, Burlingame, CA, USA) and images will be processed using Genepix Pro 4.0 image analysis software (Axon Instruments). See Figure 4 below for an...example of hybridization of a Kijabe Native African case. Native African TN BC AA “Tumor Normal” 9 Figure 4. Scanned image of Kijabe...Native African Case. The image is the result of merging the reference sample data with that from the tumor
Newman, Lori M; Berman, Stuart M
This article reviews the epidemiology of sexually transmitted disease (STD) disparities for African American communities in the United States. Data are reviewed from a variety of sources such as national case reporting and population-based studies. Data clearly show a disproportionately higher burden of STDs in African American communities compared with white communities. Although disparities exist for both viral and bacterial STDs, disparities are greatest for bacterial STDs such as gonorrhea, chlamydia, and syphilis. Gonorrhea rates among African Americans are highest for adolescents and young adults, and disparities are greatest for adolescent men. Although disparities for men who have sex with men (MSM) are not as great as for heterosexual populations, STD rates for both white and African American MSM populations are high, so efforts to address disparities must also include African American MSM. Individual risk behavior and sociodemographic characteristics of African Americans do not seem to account fully for increased STD rates for African Americans. Population-level determinants such as sexual networks seem to play an important role in STD disparities. An understanding of the epidemiology of STD disparities is critical for identifying appropriate strategies and tailoring strategies for African American communities. Active efforts are needed to reduce not only the physical consequences of STDs, such as infertility, ectopic pregnancy, chronic pelvic pain, newborn disease, and increased risk of HIV infection, but also the social consequences of STDs such as economic burden, shame, and stigma.
Masrouhi, Amara; Bellier, Olivier; Ben Youssef, Mohamed; Koyi, Hemin
We used structural, stratigraphic and sedimentologic data, together with a comparison of nearby structures and a Bouguer gravity map, to evaluate the evolution of the Bled Dogra salt structure (northern Tunisia) during the Cretaceous. Triassic salt sheets are recognized in the northwestern region of the Tunisian Atlas. These salt sheets are the result of Cretaceous thick and/or thin-skinned extension along the south Tethyan margin. The Bled Dogra salt structure is one of these submarine allochthonous salt sheets, which was emplaced during the Early Cretaceous. The geologic framework, during this period, produces conditions for a predominantly gravity-driven deformation: extension has produced space for the salt to rise; vigorous differential sedimentation created differential loading that resulted in the emplacement and extrusion of a large volume of Triassic salt and formation of large submarine salt sheets. Geologic field data suggest an interlayered Triassic salt sheet within Albian sequences. Salt was extruded at the sea floor during the Early-Middle Albian and was initially buried by Middle-Late Albian strata. The Coniacian corresponds to a second transgressive cover onto the salt sheet after the gliding of the first salt cover (Late Albian-Turonian). In addition, this northwest Tunisian area exposes evidences for salt flow and abundant slump features at the base of a northward facing submarine slope, which was probably dominant from the Early Cretaceous to Santonian. Two gravity deformation processes are recognized: gravity gliding and gravity spreading. Acting concurrently, these two processes appear indistinguishable in this geologic context. Like the present-day salt-involved passive margins - such as the northern Gulf of Mexico, the Atlantic margin of Morocco, the Brazilian Santos basin, the Angola margin, Cadiz in western Iberia, and the Red Sea - the North African Cretaceous passive margin in Tunisia provides evidences that deformation in a passive
Zhang, Feng; Wang, Jun; Ichoku, Charles; Hyer, Edward J.; Yang, Zhifeng; Ge, Cui; Su, Shenjian; Zhang, Xiaoyang; Kondragunta, Shobha; Kaiser, Johannes W.; Wiedinmyer, Christine; da Silva, Arlindo
An ensemble approach is used to examine the sensitivity of smoke loading and smoke direct radiative effect in the atmosphere to uncertainties in smoke emission estimates. Seven different fire emission inventories are applied independently to WRF-Chem model (v3.5) with the same model configuration (excluding dust and other emission sources) over the northern sub-Saharan African (NSSA) biomass-burning region. Results for November and February 2010 are analyzed, respectively representing the start and end of the biomass burning season in the study region. For February 2010, estimates of total smoke emission vary by a factor of 12, but only differences by factors of 7 or less are found in the simulated regional (15degW-42degE, 13degS-17degN) and monthly averages of column PM(sub 2.5) loading, surface PM(sub 2.5) concentration, aerosol optical depth (AOD), smoke radiative forcing at the top-of-atmosphere and at the surface, and air temperature at 2 m and at 700 hPa. The smaller differences in these simulated variables may reflect the atmospheric diffusion and deposition effects to dampen the large difference in smoke emissions that are highly concentrated in areas much smaller than the regional domain of the study. Indeed, at the local scale, large differences (up to a factor of 33) persist in simulated smoke-related variables and radiative effects including semi-direct effect. Similar results are also found for November 2010, despite differences in meteorology and fire activity. Hence, biomass burning emission uncertainties have a large influence on the reliability of model simulations of atmospheric aerosol loading, transport, and radiative impacts, and this influence is largest at local and hourly-to-daily scales. Accurate quantification of smoke effects on regional climate and air quality requires further reduction of emission uncertainties, particularly for regions of high fire concentrations such as NSSA.
Background The need to develop capacity for health services and systems research (HSSR) in low and middle income countries has been highlighted in a number of international forums. However, little is known about the level of HSSR training in Sub-Saharan Africa (SSA). We conducted an assessment at four major East and Southern African universities to describe: a) the numbers of HSSR PhD trainees at these institutions, b) existing HSSR curricula and mode of delivery, and c) motivating and challenging factors for PhD training, from the trainees’ experience. Methods PhD training program managers completed a pre-designed form about trainees enrolled since 2006. A desk review of existing health curricula was also conducted to identify HSSR modules being offered; and PhD trainees completed a self-administered questionnaire on motivating and challenging factors they may have experienced during their PhD training. Results Of the 640 PhD trainees enrolled in the health sciences since 2006, only 24 (3.8%) were in an HSSR field. None of the universities had a PhD training program focusing on HSSR. The 24 HSSR PhD trainees had trained in partnership with a university outside Africa. Top motivating factors for PhD training were: commitment of supervisors (67%), availability of scholarships (63%), and training attached to a research grant (25%). Top challenging factors were: procurement delays (44%), family commitments (38%), and poor Internet connection (35%). Conclusion The number of HSSR PhD trainees is at the moment too small to enable a rapid accumulation of the required critical mass of locally trained HSSR professionals to drive the much needed health systems strengthening and innovations in this region. Curricula for advanced HSSR training are absent, exposing a serious training gap for HSSR in this region. PMID:24365482
Rachas, Antoine; Nakouné, Emmanuel; Bouscaillou, Julie; Paireau, Juliette; Selekon, Benjamin; Senekian, Dominique; Fontanet, Arnaud; Kazanji, Mirdad
During January 2007-July 2012, a total of 3,220 suspected yellow fever cases were reported in the Central African Republic; 55 were confirmed and 11 case-patients died. Mean delay between onset of jaundice and case confirmation was 16.6 days. Delay between disease onset and blood collection could be reduced by increasing awareness of the population.
Asogwa, Kenneth; Nisenoff, Carolina; Okudo, Jerome
Foreign Accent Syndrome (FAS) is a rare phenomenon where speech is characterized by a new accent to the patient's native language. More than 100 cases with the syndrome have been published, the majority of which were associated with observed insults of the speech center. Some other cases have been described without identifiable organic brain injury, especially in patients with psychiatric illness. This paper presents a patient with schizophrenia and FAS, without any evidence of organic brain injury. FAS recurred during psychotic exacerbation and did not reverse before transfer to a long-term psychiatric facility. The case is discussed in the context of a brief review of the syndrome. PMID:26925283
Gardner, Keeba G.
This study will examine the relationship between career success outcomes of African American women and early familial factors, as well as personality traits. Using a cross-sectional case-control design. the study will use participants who self-identified as African American with two African American parents. They will be randomly selected from a…
Ruddy, Barbara E.; Mayer, Anita P.; Ko, Marcia G.; Labonte, Helene R.; Borovansky, Jill A.; Boroff, Erika S.; Blair, Janis E.
Coccidioidomycosis is caused by Coccidioides species, a fungus endemic to the desert regions of the southwestern United States, and is of particular concern for African Americans. We performed a PubMed search of the English-language medical literature on coccidioidomycosis in African Americans and summarized the pertinent literature. Search terms were coccidioidomycosis, Coccidioides, race, ethnicity, African, black, and Negro. The proceedings of the national and international coccidioidomycosis symposia were searched. All relevant articles and their cited references were reviewed; those with epidemiological, immunologic, clinical, and therapeutic data pertaining to coccidioidomycosis in African Americans were included in the review. Numerous studies documented an increased predilection for severe coccidioidal infections, coccidioidomycosis-related hospitalizations, and extrapulmonary dissemination in persons of African descent; however, most of the published studies are variably problematic. The immunologic mechanism for this predilection is unclear. The clinical features and treatment recommendations are summarized. Medical practitioners need to be alert to the possibility of coccidioidomycosis in persons with recent travel to or residence in an area where the disease is endemic. PMID:21193657
Raymond, J T; Garner, M M
From 1994 to 1999, 16 captive African hedgehogs (Atelerix albiventris), from among 42 necropsy cases, were diagnosed with cardiomyopathy. The incidence of cardiomyopathy in this study population was 38%. Fourteen of 16 hedgehogs with cardiomyopathy were males and all hedgehogs were adult (>1 year old). Nine hedgehogs exhibited 1 or more of the following clinical signs before death: heart murmur, lethargy, icterus, moist rales, anorexia, dyspnea, dehydration, and weight loss. The remaining 7 hedgehogs died without premonitory clinical signs. Gross findings were cardiomegaly (6 cases), hepatomegaly (5 cases), pulmonary edema (5 cases), pulmonary congestion (4 cases), hydrothorax (3 cases), pulmonary infarct (1 case), renal infarcts (1 case), ascites (1 case), and 5 cases showed no changes. Histologic lesions were found mainly within the left ventricular myocardium and consisted primarily of myodegeneration, myonecrosis, atrophy, hypertrophy, and disarray of myofibers. All hedgehogs with cardiomyopathy had myocardial fibrosis, myocardial edema, or both. Other common histopathologic findings were acute and chronic passive congestion of the lungs, acute passive congestion of the liver, renal tubular necrosis, vascular thrombosis, splenic extramedullary hematopoiesis, and hepatic lipidosis. This is the first report of cardiomyopathy in African hedgehogs.
... Minority Population Profiles > Black/African American > Mental Health Mental Health and African Americans Poverty level affects mental health ... compared to 120% of non-Hispanic whites. 1 MENTAL HEALTH STATUS Serious psychological distress among adults 18 years ...
Saynisch, Jan; Semmling, Maximilian; Wickert, Jens; Thomas, Maik
The Agulhas current system transports warm and salty water masses from the Indian Ocean into the Southern Ocean and into the Atlantic. The transports impact past, present, and future climate on local and global scales. The size and variability, however, of the respective transports are still much debated. In this study, an idealized model based twin experiment is used to study whether sea surface height (SSH) anomalies estimated from reflected signals of the Global Navigation Satellite System reflectometry (GNSS-R) can be used to determine the internal water mass properties and transports of the Agulhas region. A space-borne GNSS-R detector on the International Space Station (ISS) is assumed and simulated. The detector is able to observe daily SSH fields with a spatial resolution of 1-5∘. Depending on reflection geometry, the precision of a single SSH observation is estimated to reach 3 cm (20 cm) when the carrier phase (code delay) information of the reflected GNSS signal is used. The average precision over the Agulhas region is 7 cm (42 cm). The proposed GNSS-R measurements surpass the radar-based satellite altimetry missions in temporal and spatial resolution but are less precise. Using the estimated GNSS-R characteristics, measurements of SSH are generated by sampling a regional nested general circulation model of the South African oceans. The artificial observations are subsequently assimilated with a 4DVAR adjoint data assimilation method into the same ocean model but with a different initial state and forcing. The assimilated and the original, i.e., the sampled model state, are compared to systematically identify improvements and degradations in the model variables that arise due to the assimilation of GNSS-R based SSH observations. We show that SSH and the independent, i.e., not assimilated model variables velocity, temperature, and salinity improve by the assimilation of GNSS-R based SSH observations. After the assimilation of 90 days of SSH observations
Economic values of growth and feed efficiency for fish farming in recirculating aquaculture system with density and nitrogen output limitations: a case study with African catfish (Clarias gariepinus).
Besson, M; Komen, H; Aubin, J; de Boer, I J M; Poelman, M; Quillet, E; Vancoillie, C; Vandeputte, M; van Arendonk, J A M
In fish farming, economic values (EV) of breeding goal traits are lacking, even though they are key parameters when defining selection objectives. The aim of this study was to develop a bioeconomic model to estimate EV of 2 traits representing production performances in fish farming: the thermal growth coefficient (TGC) and the feed conversion ratio (FCR). This approach was applied to a farm producing African catfish (Clarias gariepinus) in a recirculating aquaculture system (RAS). In the RAS, 2 factors could limit production level: the nitrogen treatment capacity of the biofilter or the fish density in rearing tanks at harvest. Profit calculation includes revenue from fish sales, cost of juveniles, cost of feed, cost of waste water treatment, and fixed costs. In the reference scenario, profit was modeled to zero. EV were calculated as the difference in profit per kilogram of fish between the current population mean for both traits (µt) and the next generation of selective breeding (µt+Δt) for either TGC or FCR. EV of TGC and FCR were calculated for three generations of hypothetical selection on either TGC or FCR (respectively 6.8% and 7.6% improvement per generation). The results show that changes in TGC and FCR can affect both the number of fish that can be stocked (number of batches per year and number of fish per batch) and the factor limiting production. The EV of TGC and FCR vary and depend on the limiting factors. When dissolved NH3-N is the limiting factor for both µt and µt+Δt, increasing TGC decreases the number of fish that can be stocked but increases the number of batches that can be grown. As a result, profit remains constant and EVTGC is zero. Increasing FCR, however, increases the number of fish stocked and the ratio of fish produced per kilogram of feed consumed ("economic efficiency"). The EVFCR is 0.14 €/kg of fish, and profit per kilogram of fish increases by about 10%. When density is the limiting factor for both µt and µt+Δt, the
Maseko, Pam; Vale, Peter
In this interview, African Language expert Pam Maseko speaks of her own background and her first encounter with culture outside of her mother tongue, isiXhosa. A statistical breakdown of South African languages is provided as background. She discusses Western (originally missionary) codification of African languages and suggests that this approach…
Achcar, Fiona; Fadda, Abeer; Haanstra, Jurgen R; Kerkhoven, Eduard J; Kim, Dong-Hyun; Leroux, Alejandro E; Papamarkou, Theodore; Rojas, Federico; Bakker, Barbara M; Barrett, Michael P; Clayton, Christine; Girolami, Mark; Krauth-Siegel, R Luise; Matthews, Keith R; Breitling, Rainer
The African trypanosome, Trypanosoma brucei, is a unicellular parasite causing African Trypanosomiasis (sleeping sickness in humans and nagana in animals). Due to some of its unique properties, it has emerged as a popular model organism in systems biology. A predictive quantitative model of glycolysis in the bloodstream form of the parasite has been constructed and updated several times. The Silicon Trypanosome is a project that brings together modellers and experimentalists to improve and extend this core model with new pathways and additional levels of regulation. These new extensions and analyses use computational methods that explicitly take different levels of uncertainty into account. During this project, numerous tools and techniques have been developed for this purpose, which can now be used for a wide range of different studies in systems biology.
Achcar, Fiona; Fadda, Abeer; Haanstra, Jurgen R.; Kerkhoven, Eduard J.; Kim, Dong-Hyun; Leroux, Alejandro E.; Papamarkou, Theodore; Rojas, Federico; Bakker, Barbara M.; Barrett, Michael P.; Clayton, Christine; Girolami, Mark; Luise Krauth-Siegel, R.; Matthews, Keith R.; Breitling, Rainer
The African trypanosome, Trypanosoma brucei, is a unicellular parasite causing African Trypanosomiasis (sleeping sickness in humans and nagana in animals). Due to some of its unique properties, it has emerged as a popular model organism in systems biology. A predictive quantitative model of glycolysis in the bloodstream form of the parasite has been constructed and updated several times. The Silicon Trypanosome (SilicoTryp) is a project that brings together modellers and experimentalists to improve and extend this core model with new pathways and additional levels of regulation. These new extensions and analyses use computational methods that explicitly take different levels of uncertainty into account. During this project, numerous tools and techniques have been developed for this purpose, which can now be used for a wide range of different studies in systems biology. PMID:24797926
Tishkoff, Sarah A; Reed, Floyd A; Friedlaender, Françoise R; Ehret, Christopher; Ranciaro, Alessia; Froment, Alain; Hirbo, Jibril B; Awomoyi, Agnes A; Bodo, Jean-Marie; Doumbo, Ogobara; Ibrahim, Muntaser; Juma, Abdalla T; Kotze, Maritha J; Lema, Godfrey; Moore, Jason H; Mortensen, Holly; Nyambo, Thomas B; Omar, Sabah A; Powell, Kweli; Pretorius, Gideon S; Smith, Michael W; Thera, Mahamadou A; Wambebe, Charles; Weber, James L; Williams, Scott M
Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies.
Wario, Ruth Diko; Ireri, Bonface Ngari; De Wet, Lizette
Since Apple released the iPad in 2010, it has been widely adopted for teaching and learning. Its graphical user interface combined with touch screen features engages users by attracting their attention. However, the level of engagement that would influence learning is not well understood. This case study investigated the use of iPads when engaging…
Beard, Karen Stansberry
This article presents researcher reflections of a case study of a Black female deputy superintendent who made the value-driven decision to close the achievement gap in her district. I posit that she is an outlier because she is Black and female in a predominantly white male field of practice, she effectively closed the achievement gap through her…
Jenkins, Kenneth V.
The make-up of a course in African literature for high school students is discussed. It is pointed out that the course can be constructed on already familiar lines. High school students will be able to describe clearly, for example, the relationship between environment and character or the dilemma of characters caught between traditional values…
Reviews the opportunities available in the field of agriculture for African American students and notes efforts of the 136 colleges of agriculture to publicize their offerings and recruit students. Profiles six black leaders in agriculture, highlighting their achievements in research and aid to developing countries. A table provides data on annual…
Deschenes, Martin O.; Waters, Harold A.
This bibliography of resources for the teaching of African literature includes over 100 citations of books, textbooks, anthologies, plays, novels, short stories, and periodicals in French and English. Publishing house addresses, audiovisual aids, professional organizations, and a course list are also cited. The books are listed under the following…
Zambelli, Anthony B; Griffiths, Catherine A
This report describes a 6-year-old neutered male feline immunodeficiency-positive cat with repeated abdominal and thoracic effusions. The cat was diagnosed with and treated for lymphosarcoma but remission was short-lived and, on re-evaluation, a fungal peritoneal exudate was noted. Cytology of the organisms is described and the culture elucidated Cladosporium carrionii, an important cause of chromoblastomycosis. Treatment with itraconazole was unsuccessful in this case.
Ruberti, R F; Carmagnani, A L
Thirty-one cases of intraspinal tumours in the African have been described, with age, sex incidence, frequency, site and histopathology shown. Intraspinal tumours in this series are compared with the larger series. Extradural and intramedullary tumours together with cervical spine tumours appear to be more frequent in this series. There is a high incidence of dumbell tumours in the neurinomas. Sarcomas are the most common type of tumours and mainly affect the thoracic spine.
MacKinnon, Aran S
The South African mining industry relied upon a massive African migrant workforce from the rural areas. Rural transformations in this migrant labor system form an important part of the story of developing capitalism in industrializing South Africa. Yet, recent historical studies on southern African migrant and rural wage labor have paid little attention to life adjustments made by the elderly and those 'burned out' by the mines and forced to leave formal wage employment in the urban areas. The South African segregationist state's rhetoric implied that 'retired' Africans could find economic security in their designated rural reserves. Indeed, legislation sought to prohibit Africans who were not employed from remaining in the 'white' urban areas. By the 1930s, however, the reserves were rapidly deteriorating. Many elderly Africans could not retire and were forced to seek wage labor. This raises significant questions about how retirement came to be defined and experienced by Africans in South Africa during a critical period of dramatic economic decline in the 1930s and 40s, and what the underlying material circumstances of African South Africans were with regard to adaptations to employment and ageing-related life changes. In many cases, elderly Africans were forced to forgo retirement, and find wage labor, usually in the most poorly paid, least sought-after or dangerous fields of employment. This article thus seeks to illuminate critical generational dimensions of the impact of segregation and racism in South Africa prior to the formal articulation of Apartheid.
Funnyé, Allen S; Akhtar, Abbasi J; Biamby, Gisele
The purpose of this study was to determine if older African Americans are disproportionately affected by acquired immunodeficiency syndrome (AIDS), and to review the clinical impact of AIDS and the importance of prevention and treatment efforts. A review of the literature and statistics was obtained using Medline and the AIDS Public Information Data Set offered by the Centers for Disease Control and Prevention. Twenty-seven percent of the U.S. population is above the age of 50, and the number of AIDS cases in this group is growing, with African Americans accounting for the highest proportion of cases and deaths. Testing for HIV may be delayed and symptoms attributed to other illnesses. Though 5% of new cases occur in those over 50, prevention programs, testing, and the perception of risk by providers may be insufficient. There are few research studies on HIV treatment in older patients and no specific guidelines for antiretroviral treatments available. Although death rates for AIDS has been declining, adults over 50 still have the highest mortality rate. Co-morbid conditions, such as heart disease and hypertension, may require taking multiple drugs, which may complicate treatment. Increasing heterosexual transmission rates and a lack of information on HIV reinforces the need for specific prevention programs targeted toward older African Americans.
Vergunst, Richard; Kritzinger, Janis; Visagie, Surona
Background There are many factors that influence access to public health services, such as the context people live in, the existing health services, and personal, cultural and community factors. People with disabilities (activity limitations), through their experience of health services, may offer a particular understanding of the performance of the health services, thus exposing health system limitations more clearly than perhaps any other health service user. Aim This article explores how activity limitations interact with factors related to context, systems, community and personal factors in accessing public health care services in South Africa. Setting We present four case studies of people with disabilities from four low-resource diverse contexts in South Africa (rural, semi-rural, farming community and peri-urban) to highlight challenges of access to health services experienced by people with activity limitations in a variety of contexts. Methods One case study of a person with disabilities was chosen from each study setting to build evidence using an intensive qualitative case study methodology to elucidate individual and household experiences of challenges experienced by people with activity limitations when attempting to access public health services. In-depth interviews were used to collect data, using an interview guide. The analysis was conducted in the form of a thematic analysis using the interview topics as a starting point. Results First, these four case studies demonstrate that equitable access to health services for people with activity limitations is influenced by a complex interplay of a variety of factors for a single individual in a particular context. Secondly, that while problems with access to public health services are experienced by everyone, people with activity limitations are affected in particular ways making them particularly vulnerable in using public health services. Conclusion The revitalisation of primary health care and the
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Unciti-Broceta, Juan D.; Maceira, José; Morales, Sonia; García-Pérez, Angélica; Muñóz-Torres, Manuel E.; Garcia-Salcedo, Jose A.
Nicotinamide, a soluble compound of the vitamin B3 group, has antimicrobial activity against several microorganisms ranging from viruses to parasite protozoans. However, the mode of action of this antimicrobial activity is unknown. Here, we investigate the trypanocidal activity of nicotinamide on Trypanosoma brucei, the causative agent of African trypanosomiasis. Incubation of trypanosomes with nicotinamide causes deleterious defects in endocytic traffic, disruption of the lysosome, failure of cytokinesis, and, ultimately, cell death. At the same concentrations there was no effect on a cultured mammalian cell line. The effects on endocytosis and vesicle traffic were visible within 3 h and can be attributed to inhibition of lysosomal cathepsin b-like protease activity. The inhibitory effect of nicotinamide was confirmed by a direct activity assay of recombinant cathepsin b-like protein. Taken together, these data demonstrate that inhibition of the lysosomal protease cathepsin b-like blocks endocytosis, causing cell death. In addition, these results demonstrate for the first time the inhibitory effect of nicotinamide on a protease. PMID:23443665
Jackson, Andrew P; Berry, Andrew; Aslett, Martin; Allison, Harriet C; Burton, Peter; Vavrova-Anderson, Jana; Brown, Robert; Browne, Hilary; Corton, Nicola; Hauser, Heidi; Gamble, John; Gilderthorp, Ruth; Marcello, Lucio; McQuillan, Jacqueline; Otto, Thomas D; Quail, Michael A; Sanders, Mandy J; van Tonder, Andries; Ginger, Michael L; Field, Mark C; Barry, J David; Hertz-Fowler, Christiane; Berriman, Matthew
Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections.
Trimpalis, Philip; Koumandou, Vassiliki Lila; Pliakou, Evangelia; Anagnou, Nicholas P.; Kossida, Sophia
The protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping sickness in humans, which can be lethal if untreated. Most available pharmacological treatments for the disease have severe side-effects. The purpose of this analysis was to detect novel protein-protein interactions (PPIs), vital for the parasite, which could lead to the development of drugs against this disease to block the specific interactions. In this work, the Domain Fusion Analysis (Rosetta Stone method) was used to identify novel PPIs, by comparing T. brucei to 19 organisms covering all major lineages of the tree of life. Overall, 49 possible protein-protein interactions were detected, and classified based on (a) statistical significance (BLAST e-value, domain length etc.), (b) their involvement in crucial metabolic pathways, and (c) their evolutionary history, particularly focusing on whether a protein pair is split in T. brucei and fused in the human host. We also evaluated fusion events including hypothetical proteins, and suggest a possible molecular function or involvement in a certain biological process. This work has produced valuable results which could be further studied through structural biology or other experimental approaches so as to validate the protein-protein interactions proposed here. The evolutionary analysis of the proteins involved showed that, gene fusion or gene fission events can happen in all organisms, while some protein domains are more prone to fusion and fission events and present complex evolutionary patterns. PMID:23874788
The aims of this article are to present the case for the study of conflict, violence and peace in African universities and to discuss ways by which this might be organized. It begins with a discussion of the meanings of conflict, violence and peace, as used in the discipline of peace studies. The case for studying peace is then laid out, with…
This paper charts the history and debates surrounding the introduction of academic, university-based training of nurses in South Africa. This was a process that was drawn out over five decades, beginning in the late 1930s. For nurses, university training was an important part of a process of professionalization; however, for other members of the medical community, nursing was seen as being linked to women's service work. Using the case-study of the University of the Witwatersrand, one of South Africa's premier universities and the place in the country to offer a university-based nursing program, we argue that an historical understanding of the ways in which nursing education was integrated into the university system tells us a great deal about the professionalization of nursing. This paper also recognises, for the first time, the pioneers of this important process.
Traditional African healing has been in existence for many centuries yet many people still seem not to understand how it relates to God and religion/spirituality. Some people seem to believe that traditional healers worship the ancestors and not God. It is therefore the aim of this paper to clarify this relationship by discussing a chain of communication between the worshipers and the Almighty God. Other aspects of traditional healing namely types of traditional healers, training of traditional healers as well as the role of traditional healers in their communities are discussed. In conclusion, the services of traditional healers go far beyond the uses of herbs for physical illnesses. Traditional healers serve many roles which include but not limited to custodians of the traditional African religion and customs, educators about culture, counselors, social workers and psychologists. PMID:26594664
This study consisted of ectoparasites from approximately 100,000 African small mammals, representing probably more than 500 species of which many are...study of ectoparasites may provide information concerning interactions among animal reservoirs of disease, and (3) an understanding of ecological...parameters for ectoparasites and their hosts may enhance understanding of epidemiological patterns. Of the four major groups dealt with, considerably more
Saunders, Colleen J; Van Der Merwe, Lize; Cook, Jill; Handley, Christopher J; Collins, Malcolm; September, Alison V
Cartilage oligomeric matrix protein is a structural protein of the extracellular matrix, while thrombospondin-2 is a matricellular protein involved in cell-matrix interactions. Recent studies have shown that genetic variation is a significant risk factor for Achilles tendinopathy, and the genes encoding cartilage oligomeric matrix protein (COMP) and thrombospondin-2 (THBS2) were identified as good candidate genes for association with Achilles tendinopathy. This study aimed to test the association of sequence variants within these candidate genes with the risk of Achilles tendinopathy in participants from South Africa (SA) and Australia (AUS). Three-hundred and forty (133 SA; 207 AUS) control participants with no history of Achilles tendinopathy and 178 (94 SA; 84 AUS) participants clinically diagnosed with Achilles tendinopathy were genotyped for five single nucleotide polymorphisms within the COMP and THBS2 genes in this case-control study. There was no difference in genotype distributions between control and tendinopathy groups for either the THBS2 variants rs9505888, rs6422747 and rs9283850, or the COMP variants rs730079 and rs28494505 in the SA and AUS populations. As the selection of COMP and THBS2 as candidate genes was hypothesis driven, based on biological function, the possibility that other variants within these genes are associated with Achilles tendinopathy cannot be excluded.
Introduction South Africa has the largest HIV/AIDS epidemic of any country in the world. Case description National antiretroviral therapy (ART) policy is examined over the period of 1999 to 2008, which coincided with the government of President Thabo Mbeki and his Minister of Health, Dr Manto Tshabalala-Msimang. The movement towards a national ART programme in South Africa was an ambitious undertaking, the likes of which had not been contemplated before in public health in Africa. Discussion and evaluation One million AIDS-ill individuals were targeted to be enrolled in the ART programme by 2007/08. Fewer than 50% of eligible individuals were enrolled. This failure resulted from lack of political commitment and inadequate public health system capacity. The human and economic costs of this failure are large and sobering. Conclusions The total lost benefits of ART not reaching the people who need it are estimated at 3.8 million life years for the period, 2000 to 2005. The economic cost of those lost life years over this period has been estimated at more than US$15 billion. PMID:20015346
Highfield, Linda; Bartholomew, L Kay; Hartman, Marieke A; Ford, M Molly; Balihe, Philomene
When community health planners select an evidence-based intervention that has been developed and tested in one situation and adapt it for use in a different situation or community, best practice suggests needs assessment and formative research in the new setting. Cancer prevention planners who are interested in adopting and adapting evidence-based approaches need to base their choices on a sound understanding of the health or behavioral risk problem in which they mean to intervene. This requires a balancing act of weighing community information against a broader perspective from the scientific literature and using the combination to identify and adapt an evidence-based intervention program that is likely to be effective in the new setting. This report is a case study of a community and organizational assessment conducted as a foundation for selecting and recommending adaptation of an evidence-based intervention for improving mammography appointment attendance. We used an inductive sequential exploratory mixed-methods design to inform this process. The process provides a model for formative research grounding evidence-based practice for cancer control planners. Future studies that incorporate findings from needs assessment into the adaptation of the selected intervention program may promote the effective dissemination of evidence-based programs.
Hogue, Carol J R; Parker, Corette B; Willinger, Marian; Temple, Jeff R; Bann, Carla M; Silver, Robert M; Dudley, Donald J; Koch, Matthew A; Coustan, Donald R; Stoll, Barbara J; Reddy, Uma M; Varner, Michael W; Saade, George R; Conway, Deborah; Goldenberg, Robert L
Stillbirths (fetal deaths occurring at ≥20 weeks' gestation) are approximately equal in number to infant deaths in the United States and are twice as likely among non-Hispanic black births as among non-Hispanic white births. The causes of racial disparity in stillbirth remain poorly understood. A population-based case-control study conducted by the Stillbirth Collaborative Research Network in 5 US catchment areas from March 2006 to September 2008 identified characteristics associated with racial/ethnic disparity and interpersonal and environmental stressors, including a list of 13 significant life events (SLEs). The adjusted odds ratio for stillbirth among women reporting all 4 SLE factors (financial, emotional, traumatic, and partner-related) was 2.22 (95% confidence interval: 1.43, 3.46). This association was robust after additional control for the correlated variables of family income, marital status, and health insurance type. There was no interaction between race/ethnicity and other variables. Effective ameliorative interventions could have a substantial public health impact, since there is at least a 50% increased risk of stillbirth for the approximately 21% of all women and 32% of non-Hispanic black women who experience 3 or more SLE factors during the year prior to delivery.
Hogue, Carol J. R.; Parker, Corette B.; Willinger, Marian; Temple, Jeff R.; Bann, Carla M.; Silver, Robert M.; Dudley, Donald J.; Koch, Matthew A.; Coustan, Donald R.; Stoll, Barbara J.; Reddy, Uma M.; Varner, Michael W.; Saade, George R.; Conway, Deborah; Goldenberg, Robert L.
Stillbirths (fetal deaths occurring at ≥20 weeks' gestation) are approximately equal in number to infant deaths in the United States and are twice as likely among non-Hispanic black births as among non-Hispanic white births. The causes of racial disparity in stillbirth remain poorly understood. A population-based case-control study conducted by the Stillbirth Collaborative Research Network in 5 US catchment areas from March 2006 to September 2008 identified characteristics associated with racial/ethnic disparity and interpersonal and environmental stressors, including a list of 13 significant life events (SLEs). The adjusted odds ratio for stillbirth among women reporting all 4 SLE factors (financial, emotional, traumatic, and partner-related) was 2.22 (95% confidence interval: 1.43, 3.46). This association was robust after additional control for the correlated variables of family income, marital status, and health insurance type. There was no interaction between race/ethnicity and other variables. Effective ameliorative interventions could have a substantial public health impact, since there is at least a 50% increased risk of stillbirth for the approximately 21% of all women and 32% of non-Hispanic black women who experience 3 or more SLE factors during the year prior to delivery. PMID:23531847
Ramírez Rozzi, Fernando V.; Sardi, Marina L.
Although dissimilarities in cranial and post-cranial morphology among African pygmies groups have been recognized, comparative studies on skull morphology usually pull all pygmies together assuming that morphological characters are similar among them and different with respect to other populations. The main aim of this study is to compare cranial morphology between African pygmies and non-pygmies populations from Equatorial Africa derived from both the Eastern and the Western regions in order to test if the greatest morphological difference is obtained in the comparison between pygmies and non-pygmies. Thirty three-dimensional (3D) landmarks registered with Microscribe in four cranial samples (Western and Eastern pygmies and non-pygmies) were obtained. Multivariate analysis (generalized Procrustes analysis, Mahalanobis distances, multivariate regression) and complementary dimensions of size were evaluated with ANOVA and post hoc LSD. Results suggest that important cranial shape differentiation does occur between pygmies and non-pygmies but also between Eastern and Western populations and that size changes and allometries do not affect similarly Eastern and Western pygmies. Therefore, our findings raise serious doubt about the fact to consider African pygmies as a homogenous group in studies on skull morphology. Differences in cranial morphology among pygmies would suggest differentiation after divergence. Although not directly related to skull differentiation, the diversity among pygmies would probably suggest that the process responsible for reduced stature occurred after the split of the ancestors of modern Eastern and Western pygmies. PMID:21049030
This rare, cloud free view of the East African Rift Valley, Kenya (1.5N, 35.5E) shows a clear view of the Turkwell River Valley, an offshoot of the African REift System. The East African Rift is part of a vast plate fracture which extends from southern Turkey, through the Red Sea, East Africa and into Mozambique. Dark green patches of forests are seen along the rift margin and tea plantations occupy the cooler higher ground.
Introduction In 2004, Mozambique, supported by large increases in international disease-specific funding, initiated a national rapid scale-up of antiretroviral treatment (ART) and HIV care through a vertical "Day Hospital" approach. Though this model showed substantial increases in people receiving treatment, it diverted scarce resources away from the primary health care (PHC) system. In 2005, the Ministry of Health (MOH) began an effort to use HIV/AIDS treatment and care resources as a means to strengthen their PHC system. The MOH worked closely with a number of NGOs to integrate HIV programs more effectively into existing public-sector PHC services. Case Description In 2005, the Ministry of Health and Health Alliance International initiated an effort in two provinces to integrate ART into the existing primary health care system through health units distributed across 23 districts. Integration included: a) placing ART services in existing units; b) retraining existing workers; c) strengthening laboratories, testing, and referral linkages; e) expanding testing in TB wards; f) integrating HIV and antenatal services; and g) improving district-level management. Discussion: By 2008, treatment was available in nearly 67 health facilities in 23 districts. Nearly 30,000 adults were on ART. Over 80,000 enrolled in the HIV/AIDS program. Loss to follow-up from antenatal and TB testing to ART services has declined from 70% to less than 10% in many integrated sites. Average time from HIV testing to ART initiation is significantly faster and adherence to ART is better in smaller peripheral clinics than in vertical day hospitals. Integration has also improved other non-HIV aspects of primary health care. Conclusion The integration approach enables the public sector PHC system to test more patients for HIV, place more patients on ART more quickly and efficiently, reduce loss-to-follow-up, and achieve greater geographic HIV care coverage compared to the vertical model. Through the
Miles Brown, Tammy Melitta
This narrative case study research project focused on African American women principals and the leadership qualities and competencies that they bring to an urban school setting. The purpose of this study was to explore the lived experiences of African American women principals and examine the influence of this past experience, identify common…
Spencer, Natalie F.; Dowden, Angel Riddick
Gifted African American students are underrepresented and underserved in gifted education. The current article provides an overview of proper identification, racial identity development implications, psycho-social concerns and the importance of family involvement in the development of gifted African American students. A case study is presented to…
du Plessis, Andre; Webb, Paul
This qualitative interpretive exploratory case study investigated a sample of South African teachers' perceptions of the requirements for successful implementation of Information and Communication Technology (ICT) Professional Teacher Development (PTD) within disadvantaged South African township schools in the Port Elizabeth district in South…
Jordan, Diedria H.; Wilson, Camille M.
This article describes how African American students' success can be improved via the increased support of Black churches and their partnerships with public schools. Findings and implications from a comparative case study of two North Carolina churches that strive to educationally assist African American public school students are detailed. Both…
This article discusses the process of incorporating spirituality and religion into the treatment of African American clients. It addresses religious diversity within the African American community. The roles of spirituality and religion as survival and coping mechanisms for overcoming racism, adversity, and loss are emphasized. The cases presented…
Green, Calvin Earl
The purpose of this study was to investigate achievement factors of African American males on a college campus in the state of Texas, primarily a private 4-year college that serves a predominantly African American student population. The researcher used a case study approach to determine factors that affect the persistence of these college-aged…
Brown, David Byron
In an era of accountability and high standards for public schools, some African American principals decided to work in predominantly white schools. Their experiences were challenging because they were racial newcomers in schools with students different from their own race. In this case study, 12 African-American principals and assistant principals…
Ragland, Tamra C.; Harkness, Shelly Sheats
In this article, the authors provide portraits of three mathematics teachers: one European American man, one African American man, and one Middle Eastern woman. All three taught in secondary schools with predominantly African American student populations. Semi-structured interviews and observations were conducted to create a comparative case study…
Dandridge, Janae' K.
This study examines the perspective of public secondary education through the lived experiences and voices of 10 African American male students. The study was qualitative in nature and utilized an action research case study design. The researcher conducted semi structured interviews with a randomly selected group of African American male students…
Frazier, Kimberly N.
The author discusses the problem of retention of African American faculty due to tenure and promotion issues. The author outlines obstacles that African American face in the workplace while seeking tenure and promotion in academia. A case example is presented that illuminates how these stressors manifest in the academic setting and recommendations…
Conchas, Gilberto Q.; Lin, Alex R.; Oseguera, Leticia; Drake, Sean J.
Through a Multiple Marginality Framework, this exploratory case study highlights how African American male youth in an urban high school setting perceive the opportunity structure during the historic election of the first African American President. Youth optimism generated by Obama's election gives students a sense of hope despite the persistent…
Hill, K. Dara
This case study narrative examines the circumstances underlying problems of residency in an affluent Midwest suburb experiencing an unexpected influx of working class African American students. Dilemmas engender a cultural mismatch between teachers and students and discomfort with African-American males. In a controversial climate where students…
Donahue, Thomas S.
The loss of the copula in Black English Vernacular (BEV) is demonstrably traceable to norms of pidginization that have their roots in West African languages and in contact among those languages. An extensive examination of the verb systems of a number of West African languages reveals that in every case a variety of verbal forms serves the many…
Frye, Victoria; Bonner, Sebastian; Williams, Kim; Henny, Kirk; Bond, Keosha; Lucy, Debbie; Cupid, Malik; Smith, Stephen; Koblin, Beryl A.
In the United States, racial disparities in HIV/AIDS are stark. Although African Americans comprise an estimated 14% of the U.S. population, they made up 52% of new HIV cases among adults and adolescents diagnosed in 2009. Heterosexual transmission is now the second leading cause of HIV in the United States. African Americans made up a full…
Venzant Chambers, Terah T.; McCready, Lance T.
Drawing from two separate case studies, one on lower track African American students and another on gay and gender nonconforming African American male students, this article explores how students with multiple stigmatized identities make sense of and respond to their marginalization, a process we term "making space." In particular, we consider how…
King, LaGarrett Jarriel
Drawing from the historical lens of cultural memory, I examined the development of three social studies pre-service teachers' African American history knowledge. The participants were engaged in a rigorous summer reading program dedicated to learning African American history. This qualitative case study examined both pre and post interpretations…
Examines several longstanding, isolated biracial sociolinguistic situations in the coastal and Appalachian regions of North Carolina: a core community of African Americans and two case studies of isolated speakers. Compares diagnostic phonological and morphosyntactic variables for speakers representing different generations of African American and…
African-American men who have sex with men (MSM) are at increased risk of HIV infection, as are individuals with severe mental illness. This study was conducted at the behest of members of the African-American MSM community in Cleveland, Ohio, to assess the co-occurrence of HIV risk and bipolar disorder among African-American MSM. A sample of 125 participants was recruited via flyers and word of mouth at venues used by members of this community. Individuals were assessed for HIV risk and severe mental illness. Various ethical issues were presented, including participant capacity and voluntariness and the risk-benefit ratio. Divergent perspectives of the local institutional review board and the community advisory group with respect to the risks and benefits of participation required reconciliation before the study could proceed. Solutions for the resolution of such conflicts are discussed.
Odili, Julius Beneoluchi; Mohmad Kahar, Mohd Nizam
This paper proposes the African Buffalo Optimization (ABO) which is a new metaheuristic algorithm that is derived from careful observation of the African buffalos, a species of wild cows, in the African forests and savannahs. This animal displays uncommon intelligence, strategic organizational skills, and exceptional navigational ingenuity in its traversal of the African landscape in search for food. The African Buffalo Optimization builds a mathematical model from the behavior of this animal and uses the model to solve 33 benchmark symmetric Traveling Salesman's Problem and six difficult asymmetric instances from the TSPLIB. This study shows that buffalos are able to ensure excellent exploration and exploitation of the search space through regular communication, cooperation, and good memory of its previous personal exploits as well as tapping from the herd's collective exploits. The results obtained by using the ABO to solve these TSP cases were benchmarked against the results obtained by using other popular algorithms. The results obtained using the African Buffalo Optimization algorithm are very competitive. PMID:26880872
Odili, Julius Beneoluchi; Mohmad Kahar, Mohd Nizam
This paper proposes the African Buffalo Optimization (ABO) which is a new metaheuristic algorithm that is derived from careful observation of the African buffalos, a species of wild cows, in the African forests and savannahs. This animal displays uncommon intelligence, strategic organizational skills, and exceptional navigational ingenuity in its traversal of the African landscape in search for food. The African Buffalo Optimization builds a mathematical model from the behavior of this animal and uses the model to solve 33 benchmark symmetric Traveling Salesman's Problem and six difficult asymmetric instances from the TSPLIB. This study shows that buffalos are able to ensure excellent exploration and exploitation of the search space through regular communication, cooperation, and good memory of its previous personal exploits as well as tapping from the herd's collective exploits. The results obtained by using the ABO to solve these TSP cases were benchmarked against the results obtained by using other popular algorithms. The results obtained using the African Buffalo Optimization algorithm are very competitive.
Fairfax, Colita Nichols
This article is an initial exploration about the impact of ideological beliefs on helping services in the African American community. Newly infected HIV/AIDS cases place African Americans at 45% of such new cases, with African American women becoming infected at a rate 18 times that of Whites. Yet, helping services that are organic to African American women should be stronger through a discussion of cultural beliefs held in the community, where the genesis of helping services exists. Values and beliefs should be at the center of community partnerships, public media strategies, generalist-practice curricula in macro-level systems, and creating more space for relationship dialogue between African American men and women, which includes gender and racial distortions. Given the exponentially high numbers of HIV/AIDS cases in the African American community, a more earnest examination of values and beliefs is warranted.
Liebenow, J G
The Southern African Development Coordination Conference (SADCC) which unites 9 states with a combined population of 60 million, has as its objective the task of promoting economic development and realizing economic independence. In many respects the strain of neocolonialism that Southern Africa faces at this time is even more virulent than that facing West, Central, and East Africa. In the latter regions the surrender of political authority by colonial administrators frequently left the commercial, agricultural, and industrial interests of the European powers in continued control of the economies of the former colonies. The fate of economic development plans was determined by situations and decisions made in places distant from the African continent. In the case of Southern Africa, the withdrawal or expulsion of European colonialists has found whites in neighboring South Africa most eager to step into the economic breech. For most of the Southern African states this variant strain of the neocolonial virus creates a dual problem: the independent states acting separately have been no match for South Africa; and the acquiescence of independent African states in forging economic links with South Africa has impeded the liberation efforts of Africans in Namibia and the Republic of South Africa. Discussion focus turns to the challenges that confront SADCC; transport as the most significant factor accounting for the dependency of SADCC states upon South Africa; the role of minerals in dependency; other aspects of dependency; South Africa's proposed Constellation of States; the origins and objectives of SADCC; and dollars and donors. SADCC planning for economic liberation has been conducted against the background of a counterproposal advanced by South Africa's government, which put the Republic at the center of an expanded network of economic linkages within the entire southern African region. While being formally rejected, the Constellation of States scheme does have
Tauriac, Jesse J.; Scruggs, Natoschia
Perceptions of extreme, moderate, and mild forms of elder abuse among African-American women (n=25) and men (n=10) were examined. African-American respondents emphasized physical abuse when giving examples of extremely abusive behavior. Along with physical abuse, verbal abuse was the most frequently identified form of abuse, and was significantly…
Omonzejele, P F
This paper outlines the relationship between euthanasia and its ethical norms and practices in a part of West Africa. The various sub-types of euthanasia are described in detail, parallel with the role of African ethical theories in determining their relevance. The author discusses the implications of this approach relative to the social and economic state of African communities.
Wright, Dianne; Taylor, Janice D.; Burrell, Charlotte; Stewart, Gregory
This article explores the issues of African American participation in the administrative ranks of the academy. The authors find that African Americans tend to hold positions that are marginal in academic organizations, lacking power and influence, and that not much has changed over recent decades. Forces influencing this condition are explored,…
Sigmon, Scott B.
To better serve people in a counseling relationship, it is useful to understand them not only culturally, but demographically as well. This paper traces historical, religious, demographic aspects and treatment of alcohol abuse in African Americans. Historically, alcohol abuse and alcohol dependence have varied for African Americans. During the…