SEXUAL TRANSMISSION OF SLEEPING SICKNESS: A MYTH OR A FACT?
OLADOSU, OLAJUMOKE AISHAT
DOKITA Editorial Board Member
Human African trypanosomiasis (HAT), commonly referred to as sleeping sickness, has been a significant health concern in sub-Saharan Africa. Recent reports show that with the possibility of sexual transmission, the disease can no longer be neglected as a plague of developing nations of the world and a possible global pandemic. Although rare but not negligible, there have been reported cases showing the existence of sexually transmitted sleeping sickness and knowing about this newly identified route of transmission shows that there are prospects to finally curbing the disease. This article merely addresses this often neglected source of infection, and more research needs to be done in this field to have factual data and address the severity of this new transmission route.
HAT is caused by a parasitic flagellate belonging to the genus Trypanosoma. It can be differentiated from the American counterpart of the same genus, Trypanosoma cruzi, which causes Chagas disease, also known as American Trypanosomiasis. The causative organism of HAT is Trypanosoma brucei, which is divided into two subspecies –T. brucei gambiense and T. brucei rhodesiense . T. brucei brucei, a third subspecies, infects livestock.
Glossina spp. commonly referred to as tsetse fly, is the vector that carries the parasites. These flies introduce either of the two named parasites into human hosts and T. brucei brucei into animal hosts. This method is the primitive way by which humans get infected by the disease . The glossina spp. is only found in sub-Saharan Africa among cattle rearers, which explains the prevalence of the disease in this part of the world.
Recent data show that apart from this primitive route of transmission, transplacental transmission from pregnant women to fetuses occur and more importantly, there have been reported cases of sexual transmission.
Trypanosoma brucei is divided into three subspecies –T. brucei rhodesiense, T. brucei gambiense and T. brucei brucei. As established earlier, only two cause HAT. T. brucei brucei causes a sleeping sickness called nagana in livestock. T. brucei gambiense causes a chronic form of the disease lasting 1-2 years, while T. brucei rhodesiense causes an acute, rapidly fatal disease that results in death in less than a year .
The pathogenesis of sleeping sickness begins with the introduction of the parasite into the human or animal host. The parasite proliferates at the site of inoculation, resulting in the formation of an inflammatory nodule known as Trypanosomal chancre. The parasite then migrates through the lymphatic system into the circulatory system.
This disease has been classified as either Stage 1 or Stage 2. This classification depends on the presence of the parasite in the cerebrospinal fluid. Stage 1 disease is characterised by proliferation in the haemolymphatic system, which leads to generalised lymphadenopathy –the posterior cervical lymph nodes are more commonly involved, which is known as Winterbottom’s sign . Stage 2 disease is characterised by proliferation in internal organs, central nervous system and fatty tissues, which serve as reservoirs for the parasites .
African trypanosomes are unique in their ability to reside among fat cells. The ability of these parasites to reside at high levels in fatty tissues shows that they can be found in the epididymal fat body and stroma of the epididymis. However, they are not found within the testis . Their absence in the stroma of the testis does not necessarily rule out the possibility of sexual transmission since the epididymis, which conveys sperm from the testis of an infected person, contains the parasite in its walls. Furthermore, if these parasites can breach the blood-brain barrier in the brain, what is stopping them from breaching the epithelial barrier of the epididymis? This mechanism shows that HAT is transmitted sexually, but transmission probably only occurs from an infected male to a female. It is also worth noting that T. brucei has been demonstrated in the male genital tract, but traces of the parasite have not been seen in semen .
IS SEXUAL TRANSMISSION A MYTH OR A FACT?
The most substantial proof present at the moment supporting the possibility of sexual transmission is discovering infected individuals outside Africa. These individuals have not lived in tsetse infested regions for several years, further emphasising that non-tsetse routes of transmission, which include vertical transmission and sexual transmission, play a significant role in propagating this disease in these individuals . Besides, if T. cruzi has been confirmed to be sexually transmitted, why would T. brucei not act like and be transmitted similarly?
Sexual transmission of T. brucei gambiense (gHAT) has been confirmed by Rocha G. et al. in a woman and her family in 2001. The woman and her child were infected, never having visited Africa. This case was the first recorded case of sexually transmitted sleeping sickness caused by T. brucei gambiense. The patient was a 30-year-old Portuguese woman who lived in the United States of America (USA). She was admitted with malaise, pain and erythema migrans on the legs. She was initially misdiagnosed to have Lyme disease due to her presenting symptoms, and treatment was commenced, but the patient developed leucopenia, incessant fever and progressive anaemia.
Further tests were done, and a flagellated micro-organism, later confirmed to be Trypanosoma spp. was found in her bone marrow, blood and cerebrospinal fluid. Polymerase chain reaction (PCR) test and card agglutination trypanosomiasis test (CATT) was performed, and they came out strongly positive. By the time all these tests were completed, the patient started experiencing long periods of sleep followed by some episodes of agitation. The long course of the disease showed that it was the gambiense form. The patient was treated and discharged and subsequent tests years later were also negative.
This patient had never been to Africa. However, her partner had been in the military and was on a mission to Angola. He was later identified to be an asymptomatic trypanosome carrier. He was a clear source of infection. Their 19-month-old child was also tested and was found to be positive. Infection in the child was through vertical transmission from the mother. These three cases here are pointers because sexual transmission is very much actual and not hypothetical, as many believe .
PRESENTATION AND DIAGNOSIS
Most persons with HAT present with varying symptoms depending on the stage of the disease. In stage 1 disease, the patient presents with general malaise, headache and fever . Suppose the infection is caused by T. brucei rhodesiense. In that case, the disease course is more acute, and it is characterised by generalised lymphadenopathy, pancarditis, pericardial effusion, congestive heart failure and pulmonary oedema. Gambiense infection has a more insidious development that is characterised by generalised lymphadenopathy which develops following several weeks, particularly in the posterior aspect of the neck –Winterbottom’s sign.
Card Agglutination Test can diagnose stage 1 disease for Trypanosomiasis (CATT), which assays for anti-T. brucei gambiense antibody in the serum. This test is specifically sensitive to the gambiense form of infection. To confirm the diagnosis of Trypanosomiasis, the test must be accompanied by microscopic visualisation of the parasites in samples of blood, lymph and cerebrospinal fluid (in the case of stage 2 disease).
During the second stage of the disease, the patient presents with signs and symptoms showing the involvement of the central nervous system (CNS). These include headache, which becomes more severe as the disease progresses, sleeping disorders, personality changes and impaired mental function, weight loss and endocrine abnormalities. The sleeping disorders are described as drowsiness during the day and complete lassitude. The patient stays in bed all day without even leaving to eat, which contributes to weight loss. The diurnal sleepiness is accompanied by nocturnal insomnia, and there is a complete disruption of the circadian rhythm.
Four drugs have been approved for the treatment of HAT . Two of these drugs, Suramin and Pentamidine, are for treating stage 1 disease. Melarsoprol is the first line of treatment against stage 2 disease, and Eflornithine is only helpful against gambiense infection.
All these drugs have side effects. An example is Melarsoprol causes a reactive encephalopathy in one out of every five patient, and there are usually high rates of relapse after treatment . Treatment failure increases with increasing number of parasites in the cerebrospinal fluid.
SUSTAINABLE ELIMINATION OF SLEEPING SICKNESS
One of the keys to eliminating an endemic disease is knowing all the possible transmission routes of that disease. According to the latest data released by the World Health Organisation (WHO), there has been a reduction in the number of new cases of HAT. Only 1447 new cases were reported to WHO in 2017, in comparison with 2184 cases in 2016 and 9875 cases in 2009 . The most recent data show that only 980 cases were reported to WHO in 2019 for rhodesiense and gambiense forms of the disease .
The elimination of the disease means attaining zero cases, and I believe this is very much attainable. Three parties should be closely observed –the vectors, asymptomatic carriers and individuals with active infection.
Vector control has always been thought to offer hope for the control of African trypanosomiasis. It can be done by insecticide spraying on vegetation and making tsetse traps that are impregnated with insecticides. Acetone is a tsetse attracting component of the breaths of cattle and it is used as the odour bait .
The asymptomatic carriers are the second most powerful influencers of the sustainable elimination of HAT. This is where the change comes in. The focus has always been on vectors, with recent data showing the possibility of sexual transmission, asymptomatic carriers cannot be neglected. They are probably the reasons why there have not been successful elimination of the disease. These individuals show no sign of the disease. However, they transmit the disease to as many people they encounter either sexually, through blood donation or even organ donation –bone marrow transplantation .
Individuals with active infections should also not be left out of the elimination plan. Identifying these individuals and immediate commencement of targeted treatment will clear the parasite from their systems, and re-uptake by feeding tsetse flies will be impossible, thereby invariably limiting the spread of the disease.
Human African Trypanosomiasis will not be defeated in the nearest future without considering the possibility of sexual transmission. This here is the challenge for researchers, health workers and health planners. More data and a better understanding of this aspect of the disease is needed. To achieve the dream of zero cases, all hands must be on deck. Everyone should expect the unexpected, especially those that still think that the sexual transmission of sleeping sickness is hypothetical.
- Judy A. James H. Medical parasitology. In: Michael W, Brian K. (eds.) Jawetz, Melnick and Adelberg’s Medical Microbiology. 27th edition, USA. McGraw-Hill Education; 2016. p. 714-715.
- Michael P, Richard B, August S, Julio L, Alberto F, Juan C et al. The trypanosomiases. The lancet. 2003; 362 (9394): p.1469-1480 Available from: https://doi.org/10.1016/S0140-6736(03)14694-6 [Accessed 9th February 2021]
- Beverly S. African trypanosomes find a fat haven. Cell host and microbe. 2016; 19 (6): p748-749. Available from: https://doi.org/10.1016/j.chom.2016.05.022 [Accessed 9th February 2021]
- Trindade, F. Rijo-Ferreira, T. Carvalho, Printo-Neves D, F. Geugan, F. Aresta-Branco et al. Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. Cell host and microbe. 2016; 19 (6): p837-848. Available from: https://dx.doi.org/10.1016/j.chom.2016.05.002 [Accessed 9th February 2021]
- Crespillo-Andujar, M. Diaz-Menendez, M. Mora-Rillo. Evidence for previously unidentified sexual transmission of protozoan parasites. Emerging infectious disease. 2018; 24 (3): p602-603. Available from: https://doi.org/10.3201/eid2403.171838 [Accessed 11th February 2021]
- Mehlitz, D. H. Molyneux. The elimination of trypanosome brucei gambiense? Challenges of reservoir hosts and transmission cycles: expect the unexpected. Parasite epidemiology and control. 2019; 6. Available from: https://doi.org/10.1016/j.parepi.2019.e00113 [Accessed 11th February 2021]
- Rocha G, Martins A, Gama G, Brandao F, Atouguia J. Possible cases of sexual contact and congenital transmission of sleeping sickness. 2004; 363 (9404): p247 Available from: https://doi.org/10.1016/s0140-6736(03)15345-7 [Accessed 9th February 2021]
- Legros, S. Evans, F. Maiso, J. C. Enyaru, D. Mbulamberi. Risk factors for treatment failure after melarsoprol for T. brucei gambiense trypanosomiasis in Uganda. Trans R Soc Trop Med Hyg. 1999; 93 (4): 439-442. Available from: https://doi.org/10.1016/s0035-9203(99)90151-7 [Accessed February 15 2021]
- Control of Neglected Tropical Diseases. Available from: https://www.who.int/teams/control-of-neglected-tropical-diseases [Accessed 15th February 2021]
- Sustained decline in sleeping sickness cases puts elimination within reach. Available from: https://www.who.int/news/item/23-06-2020-sustained-decline-in-sleeping-sickness-cases-puts-elimination-within-reach [Accessed 22nd February 2021]
- Center for Disease Control and Prevention. Parasites- African trypanosomiasis (sleeping sickness). Available from: https://www.cdc.gov/parasites/sleepingsickness/epi.html [Accessed February 15 2021]