scholarly journals New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story

2020 ◽  
Vol 5 (1) ◽  
pp. 29 ◽  
Author(s):  
Emily A. Dickie ◽  
Federica Giordani ◽  
Matthew K. Gould ◽  
Pascal Mäser ◽  
Christian Burri ◽  
...  

The twentieth century ended with human African trypanosomiasis (HAT) epidemics raging across many parts of Africa. Resistance to existing drugs was emerging, and many programs aiming to contain the disease had ground to a halt, given previous success against HAT and the competing priorities associated with other medical crises ravaging the continent. A series of dedicated interventions and the introduction of innovative routes to develop drugs, involving Product Development Partnerships, has led to a dramatic turnaround in the fight against HAT caused by Trypanosoma brucei gambiense. The World Health Organization have been able to optimize the use of existing tools to monitor and intervene in the disease. A promising new oral medication for stage 1 HAT, pafuramidine maleate, ultimately failed due to unforeseen toxicity issues. However, the clinical trials for this compound demonstrated the possibility of conducting such trials in the resource-poor settings of rural Africa. The Drugs for Neglected Disease initiative (DNDi), founded in 2003, has developed the first all oral therapy for both stage 1 and stage 2 HAT in fexinidazole. DNDi has also brought forward another oral therapy, acoziborole, potentially capable of curing both stage 1 and stage 2 disease in a single dosing. In this review article, we describe the remarkable successes in combating HAT through the twenty first century, bringing the prospect of the elimination of this disease into sight.

2003 ◽  
Vol 31 (4) ◽  
pp. 485-505 ◽  
Author(s):  
David P. Fidler

In March 2003, the world discovered, again, that I humanity's battle with infectious diseases continues. The twenty-first century began with infectious diseases, especially HIV/AIDS, being discussed as threats to human rights, economic development, and national security. Bioterrorism in the United States in October 2001 increased concerns about pathogenic microbes. The global outbreak of severe acute respiratory syndrome (SARS) in the spring of 2003 kept the global infectious disease challenge at the forefront of world news for weeks. At its May 2003 annual meeting, the World Health organization (WHO) asserted that SARS is “the first severe infectious disease to emerge in the twenty-first century” and “poses a serious threat to global health security, the livelihood of populations, the functioning of health systems, and the stability and growth of economies.”


Parasitology ◽  
2012 ◽  
Vol 139 (7) ◽  
pp. 842-846 ◽  
Author(s):  
P. P. SIMARRO ◽  
J. FRANCO ◽  
A. DIARRA ◽  
J. A. RUIZ POSTIGO ◽  
J. JANNIN

SUMMARYDespite 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.


2019 ◽  
Vol 3 ◽  
pp. 1553
Author(s):  

Gambiense human African trypanosomiasis (gHAT) is a parasitic, vector-borne neglected tropical disease that has historically affected populations across West and Central Africa and can result in death if untreated. Following from the success of recent intervention programmes against gHAT, the World Health Organization (WHO) has defined a 2030 goal of global elimination of transmission (EOT). The key proposed indicator to measure achievement of the goal is to have zero reported cases. Results of previous mathematical modelling and quantitative analyses are brought together to explore both the implications of the proposed indicator and the feasibility of achieving the WHO goal. Whilst the indicator of zero case reporting is clear and measurable, it is an imperfect proxy for EOT and could arise either before or after EOT is achieved. Lagging reporting of infection and imperfect diagnostic specificity could result in case reporting after EOT, whereas the converse could be true due to underreporting, lack of coverage, and cryptic human and animal reservoirs. At the village-scale, the WHO recommendation of continuing active screening until there are three years of zero cases yields a high probability of local EOT, but extrapolating this result to larger spatial scales is complex. Predictive modelling of gHAT has consistently found that EOT by 2030 is unlikely across key endemic regions if current medical-only strategies are not bolstered by improved coverage, reduced time to detection and/or complementary vector control.  Unfortunately, projected costs for strategies expected to meet EOT are high in the short term and strategies that are cost-effective in reducing burden are unlikely to result in EOT by 2030. Future modelling work should aim to provide predictions while taking into account uncertainties in stochastic dynamics and infection reservoirs, as well as assessment of multiple spatial scales, reactive strategies, and measurable proxies of EOT.


2021 ◽  
Vol 15 (11) ◽  
pp. e0009992
Author(s):  
Aatreyee M. Das ◽  
Nakul Chitnis ◽  
Christian Burri ◽  
Daniel H. Paris ◽  
Swati Patel ◽  
...  

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to care.


2020 ◽  
Vol 8 ◽  
pp. 2050313X2095989
Author(s):  
Berthe Amélie Iroungou ◽  
Larson Boundenga ◽  
Laurette Guignali Mangouka ◽  
Berthold Bivigou-Mboumba ◽  
Jean Raymond Nzenze ◽  
...  

Human African Trypanosomiasis (HAT) is an infectious disease due to a protozoa parasite of the Trypanosoma genus. In West and Central Africa, this disease is caused by the subspecies Trypanosoma brucei gambiense. Several foci of this disease are currently active and causing the death of hundreds of people in endemic areas. In this article, we report two cases of gambiense HAT in one Indonesian and one Gabonese men in two historical foci of Gabon in 2019. Both patients had fever with temperatures above 38°C, an altered state of consciousness, cachexia, and multiple dermabrasions on the abdomen related to scratching lesions. The diagnostic revealed second-stage infection of both patients with T. b. gambiense; this result was confirmed by a polymerase chain reaction assay. Despite treatment with a combination of eflornithine and nifurtimox, as recommended by the World Health Organization for late-stage T. b. gambiense HAT, one of the two patients died. Thus, these cases highlight the importance of early HAT diagnosis and prompt patient care to fight effectively against this disease.


Parasitology ◽  
2014 ◽  
Vol 141 (6) ◽  
pp. 748-760 ◽  
Author(s):  
J. R. FRANCO ◽  
P. P. SIMARRO ◽  
A. DIARRA ◽  
J. A. RUIZ-POSTIGO ◽  
J. G. JANNIN

SUMMARYConsidering 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.


2021 ◽  
Author(s):  
Aatreyee Mimi Das ◽  
Nakul Chitnis ◽  
Christian Burri ◽  
Daniel H. Paris ◽  
Swati Patel ◽  
...  

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis, and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to passive care.


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