National Sleeping Sickness Control Program Research Articles

The elimination of human African trypanosomiasis: Monitoring progress towards the 2021-2030 WHO road map targets.

Human African trypanosomiasis (HAT) is a neglected tropical disease that usually occurs in rural areas in sub-Saharan Africa. It caused devastating epidemics during the 20th century. Sustained, coordinated efforts by different stakeholders working with national sleeping sickness control programmes (NSSCPs) succeeded in controlling the disease and reducing the number of cases to historically low levels. In 2012, WHO targeted the elimination of the disease as a public health problem by 2020. This goal has been reached and a new ambitious target was stated in the WHO road map for NTDs 2021-2030 and endorsed by the 73rd World Health Assembly: the elimination of gambiense HAT transmission (i.e. reducing the number of reported cases to zero). The interruption of transmission was not considered as an achievable goal for rhodesiense HAT, as it would require vast veterinary interventions rather than actions at the public health level. Data reported to WHO by NSSCPs were harmonized, verified, georeferenced and included in the atlas of HAT. A total of 802 cases were reported in 2021 and 837 in 2022. This is below the target for elimination as a public health problem at the global level (< 2000 HAT cases/year); 94% of the cases were caused by infection with T. b. gambiense. The areas reporting ≥ 1 HAT case/10 000 inhabitants/year in 2018-2022 cover a surface of 73 134 km2, with only 3013 km2 at very high or high risk. This represents a reduction of 90% from the baseline figure for 2000-2004, the target set for the elimination of HAT as a public health problem. For the surveillance of the disease, 4.5 million people were screened for gambiense HAT with serological tests in 2021-2022, 3.6 million through active screening and 0.9 million by passive screening. In 2021 and 2022 the elimination of HAT as a public health problem was validated in Benin, Uganda, Equatorial Guinea and Ghana for gambiense HAT and in Rwanda for rhodesiense HAT. To reach the next goal of elimination of transmission of gambiense HAT, countries have to report zero cases of human infection with T. b. gambiense for a period of at least 5 consecutive years. The criteria and procedures to verify elimination of transmission have been recently published by WHO. HAT elimination as a public health problem has been reached at global level, with seven countries already validated as having reached this goal. This achievement was made possible by the work of NSSCPs, supported by different public and private partners, and coordinated by WHO. The new challenging goal now is to reach zero cases by 2030. To reach this goal is crucial to maintain the engagement and support of donors and stakeholders and to keep the involvement and coordination of all partners. Along with the focus on elimination of transmission of gambiense HAT, it is important not to neglect rhodesiense HAT, which is targeted for elimination as a public health problem in the WHO road map for NTDs 2021-2030.

Integration of Traditional Healers in Human African Trypanosomiasis Case Finding in Central Africa: A Quasi-Experimental Study.

Background: Based on the premise that Africans in rural areas seek health care from traditional healers, this study investigated a collaborative model between traditional healers and the national Human African Trypanosomiasis (HAT) programs across seven endemic foci in seven central African countries by measuring the model’s contribution to HAT case finding. Method: Traditional healers were recruited and trained by health professionals to identify HAT suspects based on its basics signs and symptoms and to refer them to the National Sleeping Sickness Control Program (NSSCP) for testing and confirmatory diagnosis. Results: 35 traditional healers were recruited and trained, 28 finally participated in this study (80%) and referred 278 HAT suspects, of which 20 (7.19%) were CATT positive for the disease. Most cases originated from Bandundu (45%) in the Democratic Republic of Congo and from Ngabe (35%) in Congo. Twelve (4.32%) patients had confirmatory diagnosis. Although a statistically significant difference was not shown in terms of case finding (p = 0.56), traditional healers were able to refer confirmed HAT cases that were ultimately cared for by NCSSPs. Conclusion: Integrating traditional healers in the control program of HAT will likely enhance the detection of cases, thereby, eventually contributing to the elimination of HAT in the most affected communities.

Monitoring the elimination of human African trypanosomiasis: Update to 2016.

BackgroundHuman 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.ResultsTrends 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.DiscussionElimination 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.

On the road to elimination of Rhodesiense human African trypanosomiasis: first WHO meeting of stakeholders.

On the road to elimination of Rhodesiense human African trypanosomiasis: first WHO meeting of stakeholders.

First WHO meeting of stakeholders on elimination of gambiense Human African Trypanosomiasis.

First WHO meeting of stakeholders on elimination of gambiense Human African Trypanosomiasis.

Mapping the capacities of fixed health facilities to cover people at risk of gambiense human African trypanosomiasis

BackgroundThe emphasis placed on the activities of mobile teams in the detection of gambiense human African trypanosomiasis (HAT) can at times obscure the major role played by fixed health facilities in HAT control and surveillance. The lack of consistent and detailed data on the coverage of passive case-finding and treatment further constrains our ability to appreciate the full contribution of the health system to the control of HAT.MethodsA survey was made of all fixed health facilities that are active in the control and surveillance of gambiense HAT. Information on their diagnostic and treatment capabilities was collected, reviewed and harmonized. Health facilities were geo-referenced. Time-cost distance analysis was conducted to estimate physical accessibility and the potential coverage of the population at-risk of gambiense HAT.ResultsInformation provided by the National Sleeping Sickness Control Programmes revealed the existence of 632 fixed health facilities that are active in the control and surveillance of gambiense HAT in endemic countries having reported cases or having conducted active screening activities during the period 2000-2012. Different types of diagnosis (clinical, serological, parasitological and disease staging) are available from 622 facilities. Treatment with pentamidine for first-stage disease is provided by 495 health facilities, while for second-stage disease various types of treatment are available in 206 health facilities only. Over 80% of the population at-risk for gambiense HAT lives within 5-hour travel of a fixed health facility offering diagnosis and treatment for the disease.ConclusionsFixed health facilities have played a crucial role in the diagnosis, treatment and coverage of at-risk-population for gambiense HAT. As the number of reported cases continues to dwindle, their role will become increasingly important for the prospects of disease elimination. Future updates of the database here presented will regularly provide evidence to inform and monitor a rational deployment of control and surveillance efforts. Support to the development and, if successful, the implementation of new control tools (e.g. new diagnostics and new drugs) is crucial, both for strengthening and expanding the existing network of fixed health facilities by improving access to diagnosis and treatment and for securing a sustainable control and surveillance of gambiense HAT.

Trypanososma brucei rhodesienseSleeping Sickness, Uganda

<i>Trypanososma brucei rhodesiense</i>Sleeping Sickness, Uganda

The Human African Trypanosomiasis Control and Surveillance Programme of the World Health Organization 2000–2009: The Way Forward

One century ago human African trypanosomiasis (HAT), also known as sleeping sickness, was believed to curb the development of colonial territories. As soon as the cause of the disease was clearly identified, colonial authorities established extensive control operations, fearing an unpopulated continent and a shortage of human labour to exploit natural resources. Systematic screening, treatment, and patient follow-up was established in western and central Africa for the gambiense form of the disease while, animal reservoir and vector control was mainly implemented in eastern and southern Africa for the rhodesiense form. By the 1960s, transmission was practically interrupted in all endemic areas, providing evidence that the elimination of the disease as a public health problem was feasible and could be achieved with basic tools. Thereafter, the rarity of cases led to a loss of interest in sustained surveillance, and the risk of re-emergence of the disease was overlooked. Thus in the 1980s the disease re-emerged. By the 1990s, flareups were observed throughout past endemic areas, leading to a worrisome increase in the number of reported cases. At this time, nongovernmental organizations (NGOs) played a crucial role in the control of HAT. However, their interventions were mainly focused on remote and insecure areas. As emergency operators, their policy understandably excluded support to National Sleeping Sickness Control Programmes (NSSCPs), which resulted in (i) the establishment of substitute HAT control systems (ii), the maintenance of a large part of the population at risk out of the umbrella of NGO projects, and (iii) the difficulty for national programmes to sustain control achievements after the NGOs’ withdrawal. Concurrently, bilateral cooperation continued to support NSSCPs in some historically linked countries. Concerning HAT screening, the card agglutination trypanosomiasis test (CATT) for serological screening of populations at risk of HAT gambiense was developed during the 1970s [1], but its large-scale production encountered many problems, hindering its availability [2]; in addition, production of anti-trypanosomal drugs was seriously threatened due to the lower economic return for manufacturers. Research for new diagnostic tools and drugs was scarce [3]. Only eflornithine, initially developed for cancer treatment, was finally registered for the treatment of the gambiense form of the disease in 1990 [4]. But its cost and complex distribution and administration requirements made it inappropriate for the under-equipped peripheral health services in remote rural areas where HAT was prevalent. Only some well-funded NGOs were able to afford the cost of eflornithine treatment. During the 1990s, security constraints due to civil wars and social upheavals complicated HAT control by preventing access to a large number of HAT-endemic areas, leading to difficulties in reaching a large number of affected populations and consequently to a considerable lack of epidemiological information. The World Health Organization (WHO) Expert Committee on HAT Control and Surveillance held in 1995, in consideration of the huge uncertainties between the reported cases and the factual field situation, estimated that the true number of cases was at least 10 times more than reported. Thus from the 30,000 reported cases annually, it was estimated that some 300,000 infected individuals remained ignored in the field [5]. In 1997, the 50th World Health Assembly expressed its concerns about the major recrudescence of cases by adopting a resolution to raise awareness and national and international interest [6]. Subsequently, WHO enhanced its coordinating role and promoted networking with partners, developing a strong advocacy and awareness campaign. As a result, the private sector recognized its responsibility, which led Aventis Pharma and Bayer Health Care to grant in 2001 and 2002 a substantial support to WHO for the control and surveillance of HAT. This support included HAT drug donation and financial contributions that allowed WHO to strengthen its support to diseaseendemic countries (DECs). The importance of the various components of the epidemiology of trypanosomiasis (human, animal, vector control, agricultural activity, and livestock production) and their impact on the development of rural Africa led WHO, in 1995, to promote together with the Food and Agriculture Organization (FAO), the International Atomic Energy Agency (IAEA), and the African Union InterAfrican Bureau for Animal Resources (AUIBAR), an inter-sectoral initiative that ultimately became, in 1997, the Programme Against African Trypanosomiasis (PAAT, http://www.fao.org/ag/againfo/ programmes/en/paat/disease.html). In parallel, African heads of state and governments established during the Afri-

The Atlas of human African trypanosomiasis: a contribution to global mapping of neglected tropical diseases.

BackgroundFollowing 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.ResultsThe 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.ConclusionsFull 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 geographic distribution of the disease. Not only does the Atlas serve research and advocacy, but, more importantly, it provides crucial evidence and a valuable tool for making informed decisions to plan and monitor the control of sleeping sickness.

Towards the Atlas of human African trypanosomiasis

BackgroundUpdated, 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.MethodsUp-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.ResultsAt 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.ConclusionThe 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 demonstrate the strong need for this systematic approach to mapping sleeping sickness and point to the inaccuracy of any calculation of population at risk based on previous maps of HAT transmission areas. The Atlas of HAT will lay the basis for novel, evidence-based methodologies to estimate the population at risk and the burden of disease, ultimately leading to more efficient targeting of interventions. Also, the Atlas will help streamline future field data collection in those parts of Africa that still require it.

Population genetic structure and cladistic analysis of Trypanosoma brucei isolates

Using a novel multilocus DNA marker analysis method, we studied the population genetic structure of Trypansoma brucei stocks and derived clones isolated from animal and rhodesiense sleeping sickness patients during a national sleeping sickness control program in Mukono district, Uganda. We then performed a cladistic analysis to trace relationships and evolution, using stocks and clones recovered from geographically and temporally matched hosts, including inter-strain comparisons with T. b. gambiense stocks and clones. Our results show that while there was close genetic relatedness among parasite populations from the same geographical region, micro-heterogeneities exist between different stocks. Data are presented that indicate that not every human sleeping sickness focus may be associated with a particular human-infective trypanosome strain responsible for long-term stability of the reference focus. We provide evidence of genetic sub-structuring among type 1 T. b. gambiense stocks, which has potentially important implications for molecular epidemiology of T. brucei.

Hypogonadism in Rhodesian sleeping sickness: evidence for acute and chronic dysfunction of the hypothalamic-pituitary-gonadal axis

To investigate acute and long-term effects of Rhodesian sleeping sickness on the function of the hypothalamic-pituitary-gonadal (HPG) axis in men. An observational, cross-sectional study. Primary health care centers under care of the National Sleeping Sickness Control Program in southeast Uganda. Fifty-two male patients with sleeping sickness at different stages of treatment and 11 clinically healthy male volunteers recruited from health care personnel. Patients and controls were questioned about loss of libido and impotence. All received 100 micrograms GnRH i.v. Blood was drawn before and 30 minutes after GnRH administration. Frequency of loss of libido and impotence. Baseline T and sex hormone-binding globulin baseline and GnRH- stimulated serum LH and FSH concentrations. Loss of libido and/or impotence were present in 39% of men with active disease before therapy, whereas 84% were biochemically hypogonadal. After cure, 45% of men still were symptomatic and 45% were biochemically hypogonadal. Compared with controls (806 +/- 59 pg/mL [conversion factor to SI unit, 0.03467]; mean +/- SEM), T concentrations were decreased substantially in patients before (249 +/- 48 ng/dL), during treatment (429 +/- 56 ng/dL), and after cure (431 +/- 58 ng/dL). Corresponding baseline LH concentrations were inappropriately low and the relative LH response to GnRH was reduced both before and during treatment (794% +/- 131% versus 322% +/- 68%). Follicle-stimulating hormone concentrations increased gradually up to 8.0 +/- 1.3 mIU/mL (conversion factor to SI unit, 1.00) at the end of treatment, returning to 4.2 +/- 0.6 mIU/mL after cure. Rhodesian sleeping sickness causes acute and chronic HPG axis dysfunction. The clinical and biochemical picture suggest a combined central and peripheral hypogonadism. This is only in part reversible after cure and most likely due to direct parasitic infiltration and/or secondary inflammation causing necrosis and/or fibrosis at the pituitary and gonadal levels.