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.

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.

[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.

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.

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.

Serum lipid and lipoprotein abnormalities in human African trypanosomiasis.

We have studied the serum lipoprotein system in human African trypanosomiasis (Trypanosoma brucei gambiense infection). The study was carried out on 74 Congolense patients suffering from sleeping sickness and 34 Congolense control subjects living in the endemic region of Boko Songho. We have determined the serum concentrations of lipids (triglycerides, cholesterol, phospholipids) and apolipoproteins (apolipoprotein A-I and B), and the separation of serum lipoproteins by electrophoresis. For the patients infected with T. b. gambiense, in comparison with control subjects, the results have shown (i) a significant increase in triglyceride concentration and a decrease in cholesterol concentration; (ii) a significant rise in apolipoprotein B concentration and a significant reduction in apolipoprotein A-I concentration; and (iii) an increase in low density lipoproteins and a decrease in high density lipoproteins. We conclude, therefore, that human African trypanosomiasis is associated with marked alterations in the composition and levels of host lipoproteins.

[Where is the focus of human trypanosomiasis in Mossaka (Congo)]. / Où en est le foyer de trypanosomiase humaine de Mossaka (Congo)?

The Mossaka focus of sleeping sickness (on the Sangha, Cuvette area, in Congo) has been progressing dramatically for last years. In 1989, after a prospection we had accomplished in the focus, we had insisted on the priority to limit an extension of the disease. Since then the situation get worse, regarding to the number of patients detected (74 in 1987, 171 in 1989, 200 in 1991) and the concerned population. The number of villages where we detected patients is raised from 3 in 1987 to 12 in 1989 and 17 in 1991. If measures are not taken quickly, we can await a dramatic extension of lower Sangha focus.

[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.

[Current recrudescence of human trypanosomiasis in the Sangha focus (basin) in the Congo]. / Recrudescence actuelle de la trypanosomiase humaine dans le foyer de la Sangha (cuvette) au Congo.

In the Congo the Sangha focus of sleeping sickness caused more than 500,000 deaths in the early 20th century. Despite many years of quiescence many new cases have been detected since the early eighties. In 1987 an investigation found 43 infected patients within 5 villages (during the same year, 74 cases were detected from both investigation and passive detection). In December 1989 our further investigation found 96 new documented cases (115 for the whole year). The prevalence is increasing and the proportion of early stage in comparison with later stage is decreasing. The age diagram resembles that of the early 20th century. Despite the fact that the survey in 1989, extracted twice as many patients as in 1987 passive detection detected 99 infected patients in 1990, three times as many cases as in 1988, and places the "Sangha focus" in IId place in the Congo, after the "Bouenza focus". As only river transport is available to have access to that focus, the Congo will be faced with considerable difficulties in the future.

[Absence of epidemiologic interrelations between retroviral infection by HIV and human African trypanosomiasis (HAT)]. / Absence d'inter-relations épidémiologiques entre l'infection rétrovirale à VIH et la trypanosomiase humaine africaine (THA). Analyse de trois enquêtes cas-témoins réalisées en 1989 et 1990 en Afrique centrale.

Authors are reporting results from 3 control-case surveys carried out in sleeping sickness foci in Cameroon, Central African Republic and Congo. HIV seroprevalence rates are comparable among sleeping sickness patients and trypanonegative control persons. These results lead towards the absence of inter-relationships between sleeping sickness and retroviral infection.

[The concept of neglected disease]. / Le concept de maladie négligée.

"Neglected disease", "neglected population" and more generally "public health negligence" are emerging concepts being put forward by numerous humanitarian groups. Sleeping sickness provides a typical example to illustrate these concepts. After causing a major epidemic in the 1930s, sleeping sickness had been practically eradicated by the end of decolonization. Because of more urgent priorities, independent national governments relinquished control activities thus allowing the disease to return insidiously. By the beginning of the 1990s the situation was comparable to that prevailing in 1930 without inciting a response commensurate with the extent of the problem. Sleeping sickness is currently not a priority and, more simply, is not given proper attention because it affects only a few people living in regions presenting little economic interest. This point underlines the especially devastating combination of neglected disease and neglected population. As early as 1999 the World Health Organization with the determined support of Medecins Sans Frontieres launched a campaign not only to promote control measures for sleeping sickness at the international level but also to use initiatives in the domain to illustrate the enormous potential for progress against neglected disease. The effects of this campaign are now beginning to be felt.

[Status of sleeping sickness in 2003]. / Situation de la maladie du sommeil en 2003.

On May 3, 2001, the World Health Organization signed a major agreement with the pharmaceutical industry for the supply of drugs necessary for treatment of sleeping sickness. At that time Dr. Gro Harlem Brutland, director of the WHO, announced, "We can now look forward to halting the spread of sleeping sickness...". The purpose of this article is to take a look at the situation two years later. A first assessment showed that most national programs for the control of human African trypanosomiasis (NPCHAT) had practically become inoperative. One of the first steps in the new eradication campaign consisted of reviving these NPCHAT teams. However this goal could be achieved only insofar as awareness of the severity of the disease and of the need to act was felt at every level of decision-making. In 2001 the Pan-African Tse-Tse Trypanosomiasis Eradication Campaign (PATTEC) initiative was launched by African State leaders to promote special attention at the ministerial level, high-level training, and international cooperation sometimes involving several NPCHAT teams. Actions in the field include trials using new strategies, expert assistance for personnel throughout the duration of prospection, and screening and immediate treatment of numerous patients in outbreak areas where the disease was thought to be extinct. Although progress has not always been measurable in concrete terms, the dynamics have shifted almost everywhere.

[Sleeping sickness, forgotten illness: what are the consequences in the field?]. / Maladie du sommeil, maladie oubliée: quelles conséquences sur le terrain?

For nearly 25 years, sleeping sickness was forgotten and increasingly neglected. Research programs and control activities against human African trypanosomiasis were discontinued. Statistical studies show a constant decrease in the number of people screened and cases detected and little change in the ratios of actively versus passively diagnosed cases and of the early (blood and lymph involvement) versus late (cerebral involvement) stage cases. In the field neglect of the disease led to deterioration not only physical facilities but also human resources. As teams aged, senior members were often replaced by less than fully qualified people resulting in a decline in efficiency and organization. Many basic notions were lost and the albeit scarce innovations in diagnosis and therapy were often overlooked. When the fight against sleeping sickness was finally resumed, these factors had to be taken into account. Efforts in the field have been focused on four areas: renovation of equipment, didactic and practical training for health care personnel, development of a decision-making algorithm based on diagnostic findings, and implementation of new therapeutic protocols.

[Monitoring human African trypanosomiasis in Central Africa in 2001 and cartography: results and perspectives]. / Surveillance de la trypanosomiase humaine en Afrique Centrale en 2001 et cartographie: bilan et perspectives.

Cases of human African trypanosomiasis are distributed in changing geographical "outbreak areas" that can be visualized over time and space. Because of these variations in distribution, cartography and spatial analysis provide powerful tools for planning surveillance and control strategies. In 1996, the WHO in collaboration with the 15 most endemic countries in Central Africa undertook a program to develop a standardized inter-regional map of trypanosomiasis. This article provides a brief overview of the value of geomatic tools in public health followed by a description of the WHO program and its preliminary results. Also presented in this article is the Trypinfo site being development on the internet to increase the surveillance response-time and improve the feedback system.

[Control of human African trypanosomiasis: back to square one]. / Lutte contre la trypanosomiase humaine africaine: la boucle bouclée?

The natural history of sleeping sickness is cyclic. The first epidemic outbreak in the 19th century devastated the population and resolved spontaneously for lack of victims. Intensive development during the colonial period and the movement of population that it spawned led to another epidemic in the early 1920s that reached such severe proportions that drastic steps had to be taken. At that time, Jamot was given complete political, administrative, and financial freedom to combat the disease. This program led to the development of the mobile team concept and so-called vertically structured vector control strategy and was so successful that sleeping sickness ceased to be considered as a major public health problem at the beginning of the 1960s. In the ensuing years sleeping sickness was largely neglected. Monitoring the disease required specialized teams that were no longer considered as cost-effective. One by one the measures that had been implemented to control the disease disappeared, thus setting the scene for a new outbreak grew. In 1995, the incidence of sleeping sickness reached the same levels as in the 1920s. The current situation is a classic example of a neglected disease with a paucity of competent specialists, diagnostic tests, effective drugs, and operational facilities. It was not until 2001 that new hope appeared thanks to a combined public- and private-sector initiative allowing restructuring of treatment teams, renovation of facilities, free distribution of drugs, and research to develop new therapeutic agents. Also thanks to the PATTEC initiative, the governments of the African affected nations are showing new in interest in sleeping sickness. However the battle is far from won and much effort will be required. Time is running out and the stakes are high.

[A trial treatment with eflornithine of trypanosomiasis caused by Trypanosoma brucei gambiense in the Peoples Republic of the Congo]. / Essai de traitement de la trypanosomiase à Trypanosoma brucei-gambiense par l'eflornithine en République Populaire du congo.

In a multiclinic trial in Brazzaville, Congo, 14 patients with late-stage Trypanosoma brucei gambiense trypanosomiasis were treated with eflornithine. All cases had previously been treated with one or several courses of melarsoprol. Eflornithine treatment consisted of 400 mg/kg/day intravenously for 14 days followed by 300 mg/kg/day orally for 21 days. After treatment all patients had a disappearance of trypanosomes from cerebrospinal fluid (CSF), a normalization of CSF WBC count, and, where present prior to study, a clear, rapid and lasting amelioration of neurological signs. Neither clinical nor biological adverse effects necessitated modifying or discontinuing treatment. These encouraging results in melarsoprol-refractory cases demonstrate, despite certain logistical problems, the interest of eflornithine in the treatment of human African trypanosomiasis.

[Epidemiology of endemic leprosy in the People's Republic of the Congo. Risk factors and markers]. / Epidemiologie de l'éndemie lépreuse en République Populaire du Congo. Facteurs et marqueurs de risques.

A national prevalence survey of leprosy was made in june 1989 in Popular Republic of Congo: authors report results. The prevalence rate is 5.8% +/- 2.6% among people more than 15 years of age, and 10.5% of all forms are multibacillary. All patients are under DDS monotherapy. One overwhelming risk factor is leprosy antecedents in the family history; active case-finding and surveillance of contacts are recommended.