article: Human African trypanosomiasis (HAT) is a neglected tropical disease targeted for elimination ‘as a public health problem’ by 2020. The indicators to monitor progress towards the target are based on the number of reported cases, the related areas and populations exposed at various levels of risk, and the coverage of surveillance activities. Based on data provided by the National Sleeping Sickness Control Programmes (NSSCP), Non-Governmental Organizations (NGOs) and research institutions—and assembled in the Atlas of HAT—the World Health Organization (WHO) provides here an update to 2016 for these indicators, as well as an analysis of the epidemiological situation. Trends for the two primary indicators of elimination are on track for the 2020 goal: 2,164 cases of HAT were reported in 2016 (as compared to the milestone of 4,000 cases), and for the period 2012–2016 280,000 km2 are estimated to be at moderate risk or higher (i. e. ≥ 1 case/10,000 people/year), as compared to the milestone of 230,000 km2. These figures correspond to reductions of 92% and 61% as compared to the respective baselines (i. e. 26,550 HAT cases in the year 2000, and 709,000 km2 exposed at various levels of risk for the period 2000–2004). Among the secondary indicators, an overall improvement in the coverage of at risk populations by surveillance activities was observed. Regarding passive surveillance, the number of fixed health facilities providing gambiense HAT diagnosis or treatment expanded, with 1,338 enumerated in endemic countries in 2017 (+52% as compared to the survey completed only sixteen months earlier). Concerning rhodesiense HAT, 124 health facilities currently provide diagnosis or treatment. The broadening of passive surveillance is occurring in a context of fairly stable intensity of active case finding, with between 1. 8 million and 2. 4 million people screened per year over the period 2012–2016. Elimination of HAT as a public health problem by 2020 seems within reach, as the epidemiological trends observed in previous years are confirmed in this latest 2016 monitoring update. However, looking beyond 2020, and in particular to the 2030 goal of elimination of transmission as zero cases for the gambiense form of the disease only, there is no room for complacency. Challenges still abound, including ensuring the effective integration of HAT control activities in the health system, sustaining the commitment of donors and HAT endemic countries, and clarifying the extent of the threat posed by cryptic reservoirs (e. g. human asymptomatic carriers and the possible animal reservoirs in gambiense HAT epidemiology). WHO provides through the network for HAT elimination the essential coordination of the wide range of stakeholders to ensure synergy of efforts.
  Since the beginning of the 21st century, and following the reinforcement of control and surveillance activities against human African trypanosomiasis (HAT), the number of reported cases has been decreasing steadily [1,2]. Control activities have been coordinated and implemented by National Sleeping Sickness Control Programmes (NSSCPs) with the support of the World Health Organization (WHO), in the framework of a longstanding public-private partnership with Sanofi and Bayer, and together with bilateral cooperation, non-governmental organizations (NGOs) and other stakeholders. In this context, in 2012 WHO included the goal of eliminating sleeping sickness as public health problem by 2020 in its Neglected Tropical Diseases (NTD) roadmap [3]. Beyond 2020, WHO, in coordination with NSSCPs, set the goal of elimination of HAT as interruption of transmission by 2030 (i. e. reaching and sustaining zero HAT cases) for the gambiense form of the disease only. Global indicators and milestones were defined to monitor the progress towards elimination, that is presented every two years at WHO HAT stakeholders meetings [4–7]. Monitoring updates for 2012 and 2014 have been published [8,9], which indicated that progress towards HAT elimination met the established milestones. The present paper provides a comprehensive review of the progress up to 2016.
  The research does not directly involve human participants. No individual data is used in the paper. All the data used are provided routinely by NSSCPs, NGOs and research institutions as epidemiological information and are fully anonymized. As established by a WHO Expert Committee on control and surveillance of HAT [1], subsequently refined by the WHO HAT elimination Technical Advisory Group (HAT-e-TAG), and finally endorsed by the WHO Neglected Tropical Diseases Scientific and Technical Advisory Group (NTD-STAG), HAT elimination is to be monitored through two primary indicators: (1) the annual number of reported cases, where the target for the year 2020 is fewer than 2,000 cases [1], and (2) the area at risk reporting ≥ 1 case/10,000 people/year (calculated over a 5-year period), where the target for 2020 (more exactly, for the 5-year period 2016–2020) is a reduction of 90% as compared to the 2000–2004 baseline [10,11]. Three secondary indicators should also be followed: (a) the geographic distribution of the disease, (b) the population exposed at different levels of risk, and (c) the coverage of the exposed populations by control and surveillance activities [1]. The methods used to estimate the global indicators of HAT elimination have already been described in previous biennial updates, most notably for 2012 [8] and 2014 [9]. Additional methodological details are available from more focused publications dealing with HAT geographic distribution [12,13], HAT risk estimation [14,15], HAT cases detected in non-endemic countries [16], and HAT population at risk potentially covered by fixed health facilities with capacities for HAT diagnosis and treatment [17]. To avoid repetition, in this paper only a few methodological updates are provided. Concerning the number and geographic distribution of HAT cases reported annually, the number of people actively screened for gambiense HAT, as well as the areas and populations at risk of HAT, the present paper provides an update to 2016. As regards the estimation of the population at risk potentially covered by fixed health facilities with capacities for HAT diagnosis and treatment, a survey of the facilities was carried out between March and June 2017. Subsequently, a time-distance analysis was performed to estimate their physical accessibility for the at-risk populations [17]. In this exercise, the HAT risk distribution for 2012–2016 was used for stratification of results. The present paper includes data from the integrated passive surveillance system, which is being implemented in the context of HAT elimination, mainly in countries and areas where HAT prevalence became very low and systematic active screening is no longer cost-effective. The system turns around sentinel sites, which are selected following epidemiological criteria. Based on their respective capacities, sentinel sites perform different levels of diagnosis (clinical suspicion, serological suspicion and parasitological confirmation) on patients attending the facilities for any health problem. The HAT surveillance activity is fully integrated in the activities of the centres. Capacities for HAT diagnosis in these centres are upgraded through training, provision equipment and materials and supervision. Data are routinely collected and periodically analysed. Each HAT case detected triggers a response consisting of an active screening campaign (i. e. reactive screening) in the community of origin of the affected patient. All data used in this epidemiological update are assembled in the Atlas of HAT [13], and they have been provided by the NSSCPs, as well as by NGOs and research institutions.
  The decreasing trend observed for this indicator in previous years has continued. In 2015, a total of 2,801 new HAT cases were reported and in 2016 the figure went down to 2,164, including both gambiense and rhodesiense HAT (Fig 1). Such record low figures are 1,699 and 1,836 cases below the respective milestones as set in the WHO roadmap. Details on the HAT cases reported by country and by year (period 2000–2016) are shown in Table 1 (T. b. gambiense) and Table 2 (T. b. rhodesiense). Most of the reported cases correspond to gambiense HAT, with 2,729 and 2,110 cases in 2015 and 2016 respectively—the 2016 figure corresponding to a 92% reduction compared to 2000. The heaviest burden of gambiense HAT continues to be carried by the Democratic Republic of the Congo (DRC), which in 2016 accounted for 1,768 cases (84% of the gambiense HAT burden). Active case finding has been one of the major tools to combat T. b. gambiense transmission. The number of people actively screened in the period 2000–2016 is presented in Fig 2. Despite year-to-year variations, the overall intensity of active case finding has been fairly stable over the described time period, and it has varied between 1. 8 million and 2. 4 million people screened per year over the last five-year period (2012–2016). However, whereas in the year 2000 one HAT case was detected for every 152 people actively screened (13,400 cases actively detected / 2. 039,254 people screened), in 2016 1,981 people needed to be screened per each case actively detected (1,208 cases actively detected / 2,355,885 people screened). In addition to active screening, it is worth noting that the number of cases passively detected correspond to 49% of the gambiense HAT cases reported from 2000, varying from 39. 5% in 2000 to 44% in 2016, with a maximum of 59% in 2007. Fig 3A shows the geographic distribution of sleeping sickness cases for the 5-year period 2012–2016. The locations of active screening activities where no cases were detected are included (green dots). For the period 2012–2016,22,281 new HAT cases were reported, 87. 3% of which could be mapped at the village level. For the remaining 12. 7% of the cases, village-level mapping was not possible and mapping was done at the district or sub-district level. For the whole period 2000–2016 (2000 being the start year of the Atlas of HAT), a total number of 211,539 cases has been included in the database. Of these, 93. 2% cases have been mapped at the village level, for a total of 31,115 mapped villages. The average accuracy for mapped HAT cases is presently estimated at 1. 4 km, and it is being continuously improved.
  Data for the biennium 2015–2016 show that the epidemiological situation of HAT is following the trends observed in previous years (2000–2014), thus indicating further progress towards the goal of elimination of HAT as a public health problem by 2020. The number of cases reported has decreased by 92% since the year 2000 (from 26,550 to 2,164). The area reporting ≥ 1 case/10,000 inhabitants/year in the five-year period (2012–2016) has shrunk by 61% from the baseline period (2000–2004). Concerning gambiense HAT, the decrease in the number of cases and in the area reporting ≥ 1 case/10,000 inhabitants/year is observed in a context of sustained active screening and reinforced passive surveillance in the majority of endemic countries. Importantly, the number of health facilities providing gambiense HAT diagnosis and treatment keeps increasing, and so does their potential coverage of the at-risk population. Therefore, it can be considered that the observed trends are very likely to reflect a real abatement in disease transmission, despite the challenges always posed by under-detection. Despite the very encouraging global picture painted by the global indicators, the situation is not homogeneous, as gambiense HAT control and surveillance has weakened in a few countries, mainly owing to security constraints (e. g. Central African Republic and South Sudan). In addition, if the awareness of the disease wanes and there is an insufficient country ownership of the elimination process and goals, there could be a risk of deceleration of control and surveillance activities. The consequences of such deceleration have already been painfully experienced in the recent history of HAT. Looking at the rhodesiense form of the disease, which continues to represent a small proportion of the total number of HAT reported cases, the decreasing trend seems to be sustained, with a further reduction in the number of cases (92% from 2000 to 2016, from 709 cases to 54), and the corresponding dwindling of the area at risk. Nevertheless, these reported trends are likely to be less representative of the real situation than those for gambiense HAT. In particular, disease surveillance has weakened in such countries as Tanzania, Uganda (for rhodesiense HAT), Zambia and Zimbabwe. The widespread adoption of serological rapid tests to diagnose malaria, which have replaced microscopic examination, now prevents the accidental diagnosis of rhodesiense HAT when testing for malaria. The problem is exacerbated by a concomitant decrease in HAT-skilled staff who could maintain knowledge and awareness of the disease. These factors, compounded by the acute clinical progression of rhodesiense HAT usually prevalent in remote rural areas, are likely to result in non-negligible under-detection. An indirect indication of this possible under-detection is the fact that 8 cases (6% of the total rhodesiense HAT caseload) were diagnosed in non-endemic countries among returning tourists in 2015–2016.
  Progress in the indicators to monitor HAT elimination, backed by the Atlas of HAT, shows a robust and sustained trend towards the 2020 goal (i. e. elimination as public health problem), which appears well within reach. The positive epidemiological trend primarily owes to the efforts of NSSCP, supported by WHO and a range of committed stakeholders. To ensure the sustainability of these gains, and to pave the way for further progress, this support must be maintained. In this context, ownership of the elimination process and targets by endemic countries has to be reinforced, the development of improved tools has to continue, the availability of diagnostic tools must be ensured and WHO coordination of countries and other stakeholders must be ensured to maximize synergies. To this end, the WHO network for HAT elimination has been set up as the backbone for coordination and to facilitate the implementation of new tools and strategies. At this critical juncture in the process of elimination, the main challenge is to set up a cost-effective, adapted and sustained HAT control and surveillance strategies. This requires the progressive integration of HAT control activities in the general health system, which is often particularly difficult in those peripheral rural areas where the disease is more entrenched and the health system is weak. The sustainable elimination of HAT requires the reinforcement of the peripheral health system, a duty that falls beyond the HAT programmes and should be part of the Universal Health Coverage goal. Whilst further decreasing the gambiense HAT burden seems possible, it will be important not to neglect the rhodesiense form, despite its relatively low number of cases. Unfortunately, as opposed to gambiense HAT, very few innovative tools have been developed for rhodesiense HAT screening, diagnosis and treatment. However, it is noteworthy that a clinical trial for the use of fexinidazole in rhodesiense HAT is now in preparation stage. The zoonotic nature of rhodesiense HAT does not presently allow to envisage the interruption of its transmission, whilst for the gambiense form, zero transmission increasingly appears as an attainable target. Based on the data presented in this paper, and taking into account the epidemiological situation by country, the elimination of HAT as public health problem could be considered as already achieved in a number of HAT endemic countries. The criteria to assess and validate this status have been developed by WHO to enable the claim by countries and the formal recognition by WHO. Beyond the elimination of HAT as public health problem, there is a pressing need to develop the strategies and intensify selected interventions towards the following target, the elimination as interruption of HAT transmission (zero cases) for the gambiense form of the disease. In this prospective scenario, adapted and cost-effective strategies are bound to rely more heavily on disease surveillance, and the sustained commitment of donors will be crucial. Also, clarifying the epidemiological role played by human asymptomatic carriers, by parasites in the skin, and by the possible animal reservoirs in gambiense HAT epidemiology, will be essential, as they may pose a threat to the full interruption of transmission, and to avert its resurgence or reintroduction [24,25].
summary: Human African trypanosomiasis (HAT), also known as sleeping sickness, is a rare disease today, but throughout the 20th century it has demonstrated its potential for devastating epidemics. Over the last twenty years, substantial efforts against HAT enabled to dramatically reduce its prevalence, and the disease is now targeted for elimination by the World Health Organization (WHO). In this paper we provide an update to 2016 of the epidemiological situation, focusing on the number of reported cases, the areas and populations exposed at various levels of risk, and the coverage and intensity of surveillance activities. The trends show that attaining the 2020 target of elimination as a public health problem is within reach, with 2,164 reported cases in 2016 (as compared to the targeted milestone for the same year of 4,000 cases), and with an improved coverage of at risk populations by surveillance activities. Beyond 2020, achieving elimination of transmission for the gambiense form of the disease (targeted for 2030) will be more challenging, and it will require the sustained commitment of HAT endemic countries and donors, the adoption of innovative disease control approaches, and the coordination of a broad range of stakeholders.
keywords: medicine and health sciences
  african trypanosomiasis
  population dynamics
  tropical diseases
  geographical locations
  parasitic diseases
  research design
  tanzania
  neglected tropical diseases
  surveys
  population biology
  infectious disease control
  africa
  research and analysis methods
  public and occupational health
  infectious diseases
  zoonoses
  epidemiology
  protozoan infections
  trypanosomiasis
  people and places
  survey research
  disease surveillance
  biology and life sciences
  geographic distribution
title: Monitoring the elimination of human African trypanosomiasis: Update to 2016