The journey towards elimination of gambiense human African trypanosomiasis: not far, nor easy.

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.

Diversity of human African trypanosomiasis epidemiological settings requires fine-tuning control strategies to facilitate disease elimination.

In 2001, the World Health Organization (WHO) established a public-private partnership to fight human African trypanosomiasis (HAT). As a result of this continuous collaboration, and in addition to the coordination with nongovernmental organizations and bilateral cooperation agencies, the number of new cases of HAT annually reported by the WHO has strikingly decreased. In 2012, HAT was included in WHO's roadmap on neglected tropical diseases with a 2020 target date for elimination. Although the prevalence of HAT is decreasing and its elimination is targeted, control approaches must be adapted to the different epidemiological patterns in order to adopt the most adequate strategies to maintain their cost-effectiveness. These strategies must be flexible and dynamic in order to be adapted to the disease progression, as well as to the changes affecting the existing health facilities in transmission areas, including their accessibility, their capabilities, and their involvement in the elimination process. Considering the different patterns of transmission (Trypanosoma brucei (T.b.) rhodesiense HAT) and transmission intensity (T.b. gambiense HAT), different settings have been defined. In the case of T.b. rhodesiense, this form exists primarily where wild animals are the main parasite reservoir, and where the main parasite reservoir is cattle. In T.b. gambiense, this form exists in areas with high intensity transmission, areas with moderate intensity transmission, and areas with low intensity transmission. Criteria and indicators must be established to monitor and evaluate the actions implemented toward the elimination of HAT.

Preliminary results of the International Fusion Materials Irradiation Facility deuteron injector.

In the framework of the IFMIF-EVEDA project (International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities), CEA∕IRFU is in charge of the design, construction, and characterization of the 140 mA continuous deuteron injector, including the source and the low energy beam line. The electron cyclotron resonance ion source which operates at 2.45 GHz is associated with a 4-electrode extraction system in order to minimize beam divergence at the source exit. Krypton gas injection is foreseen in the 2-solenoid low energy beam line. Such Kr injection will allow reaching a high level of space charge compensation in order to improve the beam matching at the radio frequency quadrupole (RFQ) entrance. The injector construction is now completed on the Saclay site and the first plasma and beam production has been produced in May 2011. This installation will be tested with proton and deuteron beams either in pulsed or continuous mode at Saclay before shipping to Japan. In this paper, after a brief description of the installation, the preliminary results obtained with hydrogen gas injection into the plasma chamber will be reported.

Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis.

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.

Leishmaniasis impact and treatment access.

According to disease burden estimates, leishmaniasis ranks third in disease burden in disability-adjusted life years caused by neglected tropical diseases and is the second cause of parasite-related deaths after malaria; but for a variety of reasons, it is not receiving the attention that would be justified seeing its importance. This is especially apparent in the unnecessarily and unacceptably poor access to timely and appropriate treatment for patients. To our knowledge, this is the first publication that addresses the major issues associated with poor access to drugs for leishmaniasis and that outlines a number of feasible and practical solutions.

General design of the International Fusion Materials Irradiation Facility deuteron injector: source and beam line.

In the framework of the International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities (IFMIF-EVEDA) project, CEA/IRFU is in charge of the design and realization of the 140 mA cw deuteron Injector. The electron cyclotron resonance ion source operates at 2.45 GHz and a 4 electrode extraction system has been chosen. A 2 solenoid beam line, together with a high space charge compensation have been optimized for a proper beam injection in the 175 MHz radio frequency quadrupole. The injector will be tested with proton and deuteron beam production either in pulsed mode or in cw mode on the CEA-Saclay site before to be shipped to Japan. Special attention was paid to neutron emission due to (d,D) reaction. In this paper, the general IFMIF Injector design is reported, pointing out beam dynamics, radioprotection, diagnostics, and mechanical aspects.

[Management of Chagas disease in Europe. Experiences and challenges in Spain, Switzerland and Italy]. / Prise en charge de la maladie de Chagas en Europe. Expériences et défis en Espagne, Suisse et Italie.

The intention of this article is not to describe the illness or evaluate the number of cases diagnosed in Spain, Switzerland and Italy, nor to analyse the protocols followed in various centres. The authors rather seek to examine the main technical, local and national challenges involved in the care of patients with Chagas disease. To this end, they review concisely a number of themes which are common to the three countries. These are: the detection of disease; confirmation of the diagnosis; treatment; response to treatment; follow-up; the risk of transmission by transfusion, by organ donation and from mother to child; the psychosocial and socio-economic aspects of Chagas disease outside endemic areas; and what progress needs to be made in improving information about the condition.

Human African trypanosomiasis: Epidemiology and control.

Human African trypanosomiasis (HAT), or sleeping sickness, describes not one but two discrete diseases: that caused by Trypanosoma brucei rhodesiense and that caused by T. b. gambiense. The Gambian form is currently a major public health problem over vast areas of central and western Africa, while the zoonotic, Rhodesian form continues to present a serious health risk in eastern and southern Africa. The two parasites cause distinct clinical manifestations, and there are significant differences in the epidemiology of the diseases caused. We discuss the differences between the diseases caused by the two parasites, with an emphasis on disease burden, reservoir hosts, transmission, diagnosis, treatment and control. We analyse how these differences impacted on historical disease control trends and how they can inform contemporary treatment and control options. We consider the optimal ways in which to devise HAT control policies in light of the differing biology and epidemiology of the parasites, and emphasise, in particular, the wider aspects of control policy, outlining the responsibilities of individuals, governments and international organisations in control programmes.

The elimination of Trypanosoma brucei gambiense sleeping sickness in the focus of Luba, Bioko Island, Equatorial Guinea.

After the resurgence of sleeping sickness in Luba, Equatorial Guinea, a major campaign to control the disease was established in 1985. The campaign comprised no vector control, but intensive active and passive surveillance using serology for screening, and treatment of all parasitological and suspected serological cases. Total prevalence was used to classify villages as endemic, at risk, anecdotal and non-endemic which also allowed defining the geographic extent of the focus. Active case-finding was implemented from 1985 to 2004. The frequency of surveys was based on parasitological prevalence: twice a year during intensified control, once a year during ordinary control and once every 2 years during the control consolidation phase, when the parasitological prevalence in the whole focus fell to 0.1%. From 1985 to 1999, the indirect immunofluorescent antibody test (IFAT) was used as an initial screening tool, followed by parasitological confirmation of IFAT positive cases, and the Card Agglutination Trypanosomiasis Test (CATT) if necessary. In 2000, the IFAT was replaced by the CATT. Serum-positive individuals without parasitological confirmation were subsequently tested on serial dilution. All cases underwent lumbar puncture to determine the stage of the disease. First-stage cases were treated with pentamidine and second-stage cases with melarsoprol. A few relapses and very advanced cases were treated with eflornithine. The last sleeping sickness case was identified and treated in 1995.

A rare case of human trypanosomiasis caused by Trypanosoma evansi.

Human trypanosoma infections like the ones seen in Africa and South America are unknown in India. The only exception in literature is of two documented cases of a self-limiting febrile illness, being attributed to Trypanosoma lewisi like parasites. We are reporting an unusual case of trypanosomiasis from the rural parts of Chandrapur district in Maharashtra. An adult male farmhand who used to practice veterinary medicine also, presented with history of febrile episodes on and off since five months and drowsiness before admission to this Institute. Though routine blood and other investigations were within normal limits, the peripheral smear showed a large number of trypanosomes which morphologically resembled the species Trypanosoma evansi, the aetiological agent of surra - a form of animal trypanosomiasis. A battery of assays covering the spectrum of parasitology, serology, and molecular biology confirmed the infecting parasite to be T. evansi. Failure to demonstrate the central nervous system (CNS) involvement, as evidenced by the absence of parasite in cerebrospinal fluid (CSF) advocated the use of suramin - the drug of choice in early stage African trypanosomiasis without any CNS involvement. Suramin achieved cure in our patient. The case is being reported because of its unique nature as the patient was not immunocompromised and showed infestation with a parasite which normally does not affect human beings.

Treatment and follow-up of the first case of human trypanosomiasis caused by Trypanosoma evansi in India.

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.

Treatment and control of human African trypanosomiasis.

PURPOSE OF REVIEW: Access to treatment is a multi-step process and little progress has been made to improve treatments for sleeping sickness over the past 50 years. The current strategy is based on diagnostic tools developed in the 1960s while available drugs are still the same as those developed in the middle of the last century. Strategic opportunities can only be based on two achievements: improved diagnosis and safer drugs. This paper reviews the development of new diagnostic tools and drugs and the opportunity offered by new technologies for their further improvement. RECENT FINDINGS: The prodrug DB289 shows excellent oral activity with low toxicity for the treatment of early-stage sleeping sickness; it has recently entered phase II(b) clinical trials. The recent ability to identify and test specific host and parasite biomarkers has allowed the development of new, more-specific and sensitive, diagnostic and stage-determination tools. The accurate diagnosis of an infection by use of proteomic signature analysis has been achieved. Urinary nitrites and nitrates follow closely the increase of brain nitric oxide associated with the penetration of trypanosomes in the brain. Sleep-onset rapid eye movement-like episodes have been shown to occur at onset of late-stage trypanosomiasis. This unique disturbance of the wake/sleep cycle seems to be the first pathognomonic sign in the occurrence of late-stage trypanosomiasis. SUMMARY: Following the description of the disease, and diagnostic tools and drugs that have been used, and are still in use today, the authors show how it has influenced over time the evolution of strategies for surveillance and control. Recent developments and prospects for new, more-specific and sensitive diagnostic tools and a safer drug will undoubtedly improve the accuracy of patient recruitment and facilitate treatment, and provide ways towards new strategic opportunities.

The challenge of Trypanosoma brucei gambiense sleeping sickness diagnosis outside Africa.

Sleeping sickness is a lethal African disease caused by parasites of the Trypanosoma brucei subspecies, which is transmitted by tsetse flies. Occasionally, patients are reported outside Africa. Diagnosis of such imported cases can be problematic when the infection is due to Trypanosoma brucei gambiense, the chronic form of sleeping sickness found in west and central Africa. The low number of trypanosomes in the blood and the non-specific, variable symptoms make the diagnosis difficult, particularly when the index of suspicion is low. When the trypanosomes have penetrated into the central nervous system, neuropathological signs become apparent but even at this stage, misdiagnosis is frequent. Rapid and correct diagnosis of sleeping sickness can avoid inappropriate or delayed treatment and even death of the patient. In this article, an overview on diagnosis of imported cases of T b gambiense sleeping sickness is given, and possible pitfalls in the diagnostic process are highlighted. Bioclinical parameters that should raise the suspicion of sleeping sickness in a patient who has been in west or central Africa are discussed. Techniques for diagnosis are reviewed. A clinician suspecting sleeping sickness should contact a national reference centre for tropical medicine in his or her country, or the WHO, Geneva, Switzerland, or the Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA, for clinical consultation and provision of specific diagnostic tests. Appropriate drugs for sleeping sickness treatment are also provided by WHO and the CDC.

[Human African trypanosomiasis in an urban area: an emerging problem?]. / Trypanosomose humaine africaine en milieu urbain: une problématique émergente?

The human African trypanosomiasis is essentially a rural disease. The notification of cases in urban area has always been incidental; either a diagnosis made in town revealed a disease contracted in rural environment or it meant the preservation of a complete epidemiological cycle in a remaining urban micro-focus. In Kinshasa, in Democratic Republic of Congo, about forty cases have been notified each year. All of them came from the nearby foci of Bandundu, Lower Congo and Kasaï. In 1996 the number of cases reached suddenly 254 and today the average annual number comes up to 500 in spite of all the efforts undertaken to fight the disease. A study of cases in 1998 and 1999 shows that patients are essentially distributed in suburbs and that the most affected by the disease are the 15-49 year old ones whose job is related with agricultural or fishing activities. Two phenomena seem to explain this sudden increase: the massive inflow of refugees in outskirts of town coming from provinces where trypanosomiasis is endemic and a major economic crisis throwing out urban population in suburbs living on a subsistence micro-agriculture. These concomitant factors have contributed to the setting up of a trypanosomiasis belt around the capital. Today a strategy has to be reconsidered in order to fight against the disease in the capital itself and to make the medical staff aware of the diagnosis of a disease still unknown in their sanitary district.