Human African trypanosomiasis

Challenges to Elimination of gambiense-HAT and Comparison with rhodesiense-HAT

Human African trypanosomiasis (HAT), also known as sleeping sickness, is caused by two related parasites of Trypanosoma brucei. The parasites are transmitted by tsetse flies and has historically posed a major public health burden in sub-Saharan Africa. The chronic form, T. b. gambiense (gambiense-HAT), accounts for the vast majority of cases is predominant in the Western and Central Africa while T. b. rhodesiense is more frequent in Eastern and Southern Africa. Although these fatal infections (Untreated cases) are in the decline trend, the elimination of gambiense HAT is still challenging.

Democratic Republic of the Congo (DRC) has set a goal to eliminate the transmission of gambiense HAT by 2030. Since the cases are declined in the recent years, several biological, epidemiological, and operational challenges complicate the path toward elimination. These challenges relate to the existence of human and animal reservoirs, limitations in surveillance, and constraints in diagnosis, treatment, and integrated vector control. One health approach should be implemented to achieve the goal to eliminate by the target year. This integrated approach includes the control of human and animal reservoirs, extensive surveillance strategy, and control strategies on diagnosis, treatment and vector.

 

1. Human and Animal Reservoirs

Human is the primary reservoir that plays a key role in transmission of gambiense-HAT disease making a major concern for control strategy. In addition, studies suggest that asymptomatic human carriers may harbor parasites for extended periods without detectable parasitemia using standard diagnostics. These individuals can continue transmission of this infection silently, acting as “cryptic reservoirs” (Buscher et al. 2018). These infections even challenge for elimination because they escape the routine screening programs leading undiagnosed.

Likewise, gambiense HAT has animal reservoirs as well. Animal reservoirs—including pigs, dogs, and other domestic or wild animals—have been found to carry T. b. gambiense in some endemic areas. Although their epidemiological significance remains unclear, experimental and field data indicate that animals could contribute to transmission cycles, particularly in regions where human cases are declining (Mehlitz et al., 2019). If animals maintain the parasite independently of humans, elimination strategies focused solely on human case detection may be insufficient. The unpredictability of transmission cycles, including human and potential animal reservoirs, underscores the warning to “expect the unexpected” (Mehlitz et al., 2019). These hidden reservoirs represent a major obstacle to achieving transmission chain blockage.

 

2. Surveillance Strategies

The surveillance of entire communities has been highly successful in reducing disease burden during outbreak and higher number of cases using traditional active screening campaigns. However, a number cases are dropping, an alternative, sustainable and effective control strategy is utmost which is logistically challenging. As a consequence, health care center based screening is an alternative cost effective option. This method shifts toward passive surveillance, is necessary but presents difficulties. Lacking proper training for healthcare workers, resources and facilities at health care centers may miss the recognition of parasites and diagnosis gambiense HAT, especially when encounter with patients showing nonspecific early symptoms. Moreover, reduced awareness as cases decline can lead to underreporting and delayed diagnosis.

New approaches include:

1. Targeted surveillance, focusing on high-risk populations and historical foci
2. Serological screening tools (e.g., rapid diagnostic tests) to identify suspected cases
3. Molecular diagnostics, which may detect low-level infections even in early stage of infection but remain expensive and technically demanding

Additionally, xenomonitoring (presence of parasites in tsetse flies) may be used as supplementary screening strategy to detect ongoing transmission (Rotureau et al., 2013). However, implementing such methods at scale remains challenging. A major issue is maintaining sensitive surveillance systems in low-prevalence settings.

 

3. Control Strategies

Diagnosis

The diagnosis of gambiense-HAT is based on a two-step process: serological screening followed by parasitological confirmation. Although the method is effective, it has few limitations including low sensitivity while detecting low parasitemia infections. In addition, skilled manpower and well facilitated laboratory infrastructure are required. The most important challenge is identifying latent infections or infections with non-specific symptoms. Recent developments, such as oral treatments that may not require parasitological confirmation, could simplify diagnostic pathways, but their integration into elimination programs requires careful evaluation, particularly in the context of evolving control strategies and uncertainties around transmission dynamics and reservoirs (Mehlitz et al., 2019; Buscher et al.).

 

Treatment

The introduction of safer and simpler drugs improves the treatment significantly. Oral therapies of antiparasitic drug; fexinidazole allow the effective treatment of a number of outpatients reducing logistical burdens. However, ensuring accessibility to remote areas, managing treatment adherence and avoiding drug resistant remain still challenging. Furthermore, treating asymptomatic carriers—if identified—raises ethical and operational questions.

 

Integrated Vector Control

The tsetse fly is the sole vector of HAT, making vector control a critical component of elimination strategies. A multiple approach is necessary to control the vectors that not only includes tsetse fly biting but also reduce their population. The use of insecticide-treated targets and traps, aerial spraying and sterile insect technique (SIT) are some of those methods used for vector control. Recent innovations such as “tiny targets” have proven highly cost-effective in reducing tsetse populations. However, sustaining vector control over large and often inaccessible areas is difficult. Ecological factors, such as tsetse habitat diversity and reinvasion from untreated areas, complicate efforts (Van den Bossche et al., 2011). The complicity of transmission dynamics of gambiense HAT also stays major obstacle on vector control.

The transmission efficiency of the vector depends on vector competence that is influenced by complex biological interactions within the fly, including different parasite development stages (procyclic forms, metacyclic forms) (Rotureau et al., 2013).

 

Would the same strategy work for rhodesiense-HAT?

The above elimination strategy used for gambiense-HAT may not be directly applicable to T. b. rhodesiense (rhodesiense-HAT), which differs fundamentally in its epidemiology. Rhodesiense-HAT is an acute zoonotic disease, primarily infecting Eastern and Southern Africa that accounts for only 8% of reported cases. The number of cases are also much less than gambiense-HAT. In addition, wildlife and livestock serving as the primary reservoirs for rhodesiense-HAT, rather than humans gambiense-HAT. Transmission occurs at the interface between wildlife, livestock, and human populations (Auty et al., 2016). Consequently, humans are incidental hosts, not the main reservoir. Only eliminating human cases does not interrupt transmission, rather animal reservoirs sustain the parasite independently and maintain within the animal population. Hence, a slight different approach should be implemented to eliminate rhodesiense-HAT transmission.

Control strategies must therefore focus on integrated approaches, focusing on treatment and proper management of livestock as cattle are major reservoirs. Vector control in livestock and wildlife areas are essential although vector control in wildlife is the most challenging one. Moreover, the physical barrier for human-animal interfaces should be clearly defined to avoid close interactions.

The concept of a Progressive Control Pathway for African Animal Trypanosomosis (AAT) highlights the need for stepwise, multisectoral strategies targeting animal reservoirs (Diall et al., 2017).

Unlike gambiense-HAT, where elimination of transmission is theoretically feasible due to the predominance of human reservoirs, rhodesiense-HAT control is more about reducing incidence rather than complete elimination. The ecological complexity and involvement of wildlife make eradication extremely difficult.

 

Concluding remark

The decline of gambiense-HAT in the DRC is a landmark public health achievement, yet reaching the 2030 goal of zero transmission remains a demanding effort. There is a complex set of hurdles to face: "silent" or cryptic human infections that go undetected, the looming possibility of animal reservoirs, and the logistical difficulty of maintaining robust surveillance and treatment in high-risk areas. Overcoming these barriers will require more than just persistence; it demands flexible strategies and a new generation of diagnostic and vector control tools. A one health approach should be adopted that treats human, animal, and environmental health as one interconnected system where all stakeholders work together to achieve the goal.

The situation with rhodesiense-HAT, however, is a different story entirely. Because this form of the disease is zoonotic—meaning it cycles through animals—human-focused medical care alone won't be enough. To make a real impact, only treating infected human population may not work, rather control of infections in wild and domestic animals within their natural habitats may be the mainstay. Even then, given the current tools at our disposal, complete elimination remains a distant and difficult target.

Adopted from CDC