African Trypanosomiasis aka African Sleeping Sickness
African Trypanosomiasis aka African Sleeping Sickness
Human African Trypanosomiasis (HAT) is an infectious parasitic disease transmitted by vectors. The main problem biologists are trying to solve for this disease is to find a cure or at the very least, prevent it by controlling the spread of it. The parasites that cause this disease are Trypanosoma brucei rhodensiense in Southern/Eastern Africa and Trypanosoma brucei gambiense in Northern/Western Africa. Tsetse fly (Glossina genus) bites are the primary biological vectors for this. The bites can only transport the disease if they have already acquired the infection from animals or human beings affected by the protozoa.
Tsetse flies are only found in Sub-Saharan Africa but only particular species transmit the disease. Moreover, in many regions the flies are found but sleeping sickness is not. People living in rural populations where transmission does occur are most exposed to the disease. This is usually because they depend on agriculture, fishing or hunting and are more unprotected to the tsetse fly.
The sleeping sickness develops when a tsetse fly bites an infected person. “Flies can remain infected for life (2-3 months). Tsetse flies inject over 40,000 metacyclic trypanosomes when they take a blood meal. The minimum infective dose for most hosts is 300-500 organisms, although experimental animals have been infected with a single organism.”  [see figure 1 for more detail]
Inside the fly the parasites then divide to reproduce, maturing in the fly’s gut. After they have matured, they move to the salivary glands and become infectious. The next time the tsetse fly bites another person, they will become infected by either the T.b.gambiense (T.b.g) or T.b.rhodesience (T.b.r).  “T.b.g. accounts for 95% of reported cases of sleeping sickness.”  [see figure 2 for more detail].
- It causes a chronic infection.
- The symptoms may take months or even years to appear.
- When the symptoms do emerge, the disease is most likely in its advanced stage where the central nervous system (CNS) is affected. 
- The symptoms include fever, severe headache, extreme fatigue, aching muscles and joints and swollen lymph nodes.
- This particular species of the parasite, when untreated, will usually takes 3 years to kill and very rarely lasts longer than 6-7 years.
- It causes an acute infection.
- Symptoms generally appear in 1-2 weeks of the infective bite.
- The actual symptoms are very similar to those of T.b.gambiense; nonetheless some patients may also develop a rash. 
- Due to the speed of the disease, the effects on the heart can become fatal before the disease has a chance to spread to the brain. 
- The parasite can attack the CNS only after a few weeks of contamination
- This will eventually cause mental health problems. An untreated infection will mean death within months. 
Diagnosis is made in three steps. Firstly, a person is screened for any potential infections. This means using serological tests (only for T.b.g) and checking for medical signs – typically swollen cervical glands. The next step in the diagnosing process is confirming if the parasite is present. The final step includes determining how far the disease has progressed – what stage it is at. This can be done through analysing the result cerebrospinal fluid tests. Using the results, the method of treatment is decided.
A problem with the diagnosis procedure is that it requires highly trained professionals and major investment.  These types of resources are limited in Africa and that is why “despite the WHO projection of 60 million people at risk in Africa, only a fraction of the population at risk is currently under surveillance, and relatively few cases are accurately diagnosed annually (Knudsen and Slooff, 1992).”  (WHO – World Health Organisation)
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Solutions: Main – Drugs
Currently the main method used to treat people with the condition of HAT is drugs. At the first stage the drugs used are not very toxic and are easier to allocate with correct dosages. The earlier HAT is identified, the more probable the cure becomes. Pentamidine is used for the first stage of T.b.g. Although it produces some side-effects, “it is well tolerated by patients”. Suramin is used to treat the first stage of T.b.r and produces side-effects, such as, allergic reactions and undesirable effects in the urinary tract. The second stage treatment drugs are much more toxic and much more difficult to administer. Furthermore, success of the treatment in second stage depends on the drugs because they have to cross the blood-brain barrier to reach the protozoa.
The oldest drug in second-stage is called Melarsoprol (discovered in 1949). This drug can cause reactive encephalopathy (encephalopathy syndrome).  Encephalopathy means brain damage, disease or malfunction. The main symptom for this is an altered mental state. Often this can be defines as poor judgement, poor coordination of movement and inattentiveness. Other symptoms include legarthy (abnormal drowsiness), dementia, muscle-twitching, seizures and coma.  Encephalopathy can be fatal to a percentage of people taking this drug. That percentage ranges from 3% up to 10%. Finally, resistance to the drug Melarsoprol has been identified, especially in central Africa. 
Elfornithine is a newer drug and was registered in 1990. It is less toxic than Melarsoprol however it is futile against T.b.r. . Regrettably, the drug is not in production anymore and even though WHO is looking for alternative producers, the future cost of the drug is estimated to rise to US$ 60 per bottle.  Recently a combination of Elfornithine and Nifurtimox was introduced to treat HAT (2009) and while it is not registered for African Trypanosomiasis it is included in the WHO List of Essential Medicine. 
Very recently, (2012) an article was published regarding UK researchers who have discovered how the drugs used to treat sleeping sickness work at a molecular level. A genetic screening technique called RNA interference target sequencing (RIT-seq) was used to screen a total of 7500 genes. The researchers found a total of 50 genes (therefore 50 proteins) that are related to drug action and resistance. Using this information, the interaction of the drugs with parasites can be analysed and then exploited to form new and/or improved drugs to tackle resistance. 
A study done on “Melarsoprol versus Elfornithine for treating late-stage Gambian Trypanosomiasis in the Republic of the Congo” was published in a bulletin of the WHO. The outcomes of death and relapse within 1 year of discharge were analysed during the treatment. 288 patients were treated with Elfornithine, 311 patients were treated with the standard Melarsoprol regimen and 62 patients treated with a 10 day short-course Melarsoprol regimen between April 2001 and April 2005. This clearly proves that Elfornithine is the best drug used to treat late-stage T.b.r. Moreover, the incidences of relapse show that the effectiveness of the Melarsoprol treatment has reduced. Elfornithine is less likely to cause deaths too. This is clearly proven by the risk factor ratio for death. “when compared with Elfornithine, standard Melarsoprol was found to be a risk factor for both death (odds ratio (OR) = 2.87; 95% confidence interval (CI) = 1.03-8.00) and relapse (hazard ratio (HR) = 2.47; 95% CI = 1.22-5.03)”.  [see figures 4 and 5]
An economic problem in manufacturing Melarsoprol is that it is uncertain if it will be continued in production for commercial reasons. Moreover, rises in prices of medication will result in less medication being provided at the same budget. It is well known that Africa is very far behind in the developing world and it will become increasingly harder to pay for medicine for such a large population. “There are also problems associated with manufacturing the raw material required for Melarsoprol (containing arsenic) which is highly contested for ecological reasons.”  Manufacturing arsenic whilst endeavouring to maintain good environmental health can be difficult.
An unfortunate implication of this drug that it can cause reactive encephalopathy (encephalopathic syndrome) and this can be fatal to a percentage of people taking this drug. That percentage ranges from 3% up to 10%. In addition to this, the medicine is derived from arsenic and can cause arsenic poisoning which is also fatal.  This raises the ethical issue of double effect because although the medicine may help cure the patient of HAT, it may then doom the patient to death by arsenic poisoning or encephalopathic syndrome.
Risks and Benefits of Drugs:
One of the risks of HAT is that is can be fatal even when they do cure a patient. “Between 5% and 20% of those treated die of complications from the injected drug.”  This can be a problem for regular use treatments. Another risk is that growing resistance to drugs means that HAT may become even more lethal than it is already. Unfortunately, growing expenses of drugs also means that only a fraction of the population are given medical help to treat them.
On the other hand, one of the benefits of drugs is that if the disease is discovered in an early stage, the first stage drugs can be used. These are less toxic, easier to administer and not fatal. Moreover, new techniques and therapies are being found to tackle drug resistance. In addition to this, many organisations provide drugs for free to help tackle economic difficulties. An example of this is the World Health Organisation – WHO.
Alternative Solution 1 – Prevention and Control
An alternative solution is prevention and control of the vector population. This solution is important because currently there is no vaccine and no definite measure against drug resistance. Therefore this approach ensures that the number of patients does not go out of control. Proof of this is in the epidemics have broken out previously. The largest of these was in Uganda and the Congo Basin between 1896 and 1906. After that there was another one in 1920 and it was controlled due to mass screening of the people at risk. Due to this the disease had almost disappeared by the middle of the 1960’s. Surveillance was relaxed and the most recent epidemic occurred in 1970. Over the last 30 years, the disease managed to reappear in several areas. However, the continuously increasing number of cases started decreasing in the 1990’s because of national control programs, WHO (World Health Organisation) and other NGO’s (nongovernmental organisations).  In 1994, it was approximated that there were 150,000 cased in Congo. In some villages the frequency of the disease was up to 70% (Cattand, 1994).  Moreover, “in 1998, almost 40,000 cases were reported, but estimates were that 300,000 cases were undiagnosed and therefore untreated.” This is a drastic improvement to the recent figures which state that in 2009 “the number of cases reported has dropped below 10,000 (9,878) for first time in 50 years. This trend has been maintained in 2010 with 7,139 new cases reported. The estimated number of actual cases is currently 30,000.”
There various measures are taken to control the vector population. First is chemical control and it is the most popular method used. Residual insecticides such as organochlorines, pyrethroids and avermectins are used to target areas where fly-bites are likely. This mostly involves dense and humid areas but these are not the only ones targeted. The insecticides can be spread aerially or from the ground. However, organochlorines and organophosphates have an environmental implication because they can get into the food chain and become highly toxic to mammals and other vertebrates. Due to this reason, they have now been banned from widespread outdoor spraying. For the same reason, pyrethroids are preferred because they degrade rapidly in soil and aren’t harmful to the surrounding environment. Barrett (1997) showed that over 200,000 km2 of tsetse-infested land was cleared by ground spraying in West Africa. Although the benefits of this include being cost-effective and successful, the risk represents a dangerous circumstance. Because there is variation in the types of wild tsetse flies, the use of insecticides may lead to only high resistant flies surviving and reproducing to form a type of super-fly. Proof of the possibility of this scenario is in the superbug MRSA.
The next control method is targets and traps. These are used to kill and weaken the vectors through insecticides and other trapping methods. [see figure 3]. A benefit of these traps is that they are very affordable and practical. Therefore they can be used in very poor areas. “190 homemade NG2B traps were deployed over 100 km2, and a 98-99% G. pallidipes reduction was achieved over a 10 month period.” Brush clearing is another method used lower tsetse fly populations. This method was used make areas uninhabitable for tsetse flies. These methods achieved success but had many environmental implications such as soil erosion and decreased soil fertility. Therefore they were deemed unsuitable as a long-term tactic. 
Personal prevention methods can also be used. Park rangers, locals (especially in rural parts) and tourists are all advised to take these helpful measures. These include:
- Wearing long sleeved shirts and medium length trousers/pants.
- Wearing neutral colour as if to camouflage so that the flies aren’t attracted.
- Inspecting vehicles before entering because the flies like dust and motion.
- Avoiding bushes
- Use insect repellent.
Alternative Solution 2 – Future Research
Another alternative is future research into bacteria being genetically modified to attack the parasite. This ‘good bacteria’ is found in the gut, muscle and salivary glands of the tsetse fly. Researchers in Belgium have found a way to use these bacteria to harm the protozoa by releasing antibody fragments against the trypanosome. "When we looked at living trypanosomes under conditions that mimic the inside of the tsetse gut, the Sodalis-expressed nanobodies were biologically active and bound all over the surface of the parasite. Now that we know this technique works we are looking at making nanobodies which will destroy or block development of the parasite in the tsetse fly gut," Van Den Abbeele, from the Institute of Tropical Medicine, Antwerp, said. However work is still needed to improve and perfect the process as it is still in the developing stage. [7 & 8]
In conclusion, I believe that currently the best solution is prevention and control. This is because good control nearly wiped out this disease in the 1960’s. However, relaxing the control meant that the disease reappeared. This method is cost-effective, can be utilised in extremely poor locations and don’t have many implications. The benefits outweigh the risks. I believe that although the main focus should be on prevention and control, drugs are always going to be needed for any who already have the infection or any who may get infected later. Alternative solution 2 was very promising and after the process has been developed and perfected, it may even show promise of a future vaccine to eliminate risk of disease. This could be possible by developing antibodies in humans or injecting them with antibodies to build up immunity.
- World Health Organisation – Human African Trypanosomiasis
Date accessed: 02/03/2012
This source is extremely reliable as it is the directing and coordinating authority responsible for health within the United Nations. Furthermore, it provides leadership on global health matters and sets the standards and norms whilst shaping the agenda for health-related research. It is an accepted reliable source as proven by the second source – a published volume – where data from WHO was used. An example of this is a quote I used – “despite the WHO projection of 60 million people at risk in Africa, only a fraction of the population at risk is currently under surveillance, and relatively few cases are accurately diagnosed annually (Knudsen and Slooff, 1992).” The WHO article I used was valid too as it listed January 2012 as the article date. That confirms that it is the most likely to be the most recent information provided.
- Parasitic Diseases – Fifth Edition – Chapter 6
URL: (figure 2)
Publisher: Apple Trees Productions
Publish Date: 2005
A reliable source as the content of the book is officially been published and the researchers who wrote this volume work in the field of infectious diseases. Therefore, they likely have good experience that they can input into the edition. The textbook is intended as a classroom guide for medical students and an occasional guide for a practitioner. This further confirms the proof for its reliability. In the case of validity, this source is not up-to-date. The textbook was published in 2005, meaning that, in the rapidly growing medical world, the information is subject to era-dependence. Not all information will be applicable to current circumstances.
- The British Medical Association – Complete Family Health Encyclopaedia (not web-based)
Date published: 1995
Author: Tony (Medical Editor) Dr. Smith
- CDC – Centres for Disease Control and Preservation
Date accessed: 03/03/2012
- MM Student Projects – Health resource for Student Travellers
Date accessed: 04/03/2012
- Nature – International Weekly Journal of Science
Date accessed: 04/03/2012
- BBC – News Article
Date accessed: 05/03/2012
- News Track India – News Article
Date accessed: 05/03/2012
- MedicineNet, Inc. - Owned and Operated by WebMD and part of the WebMD Network
Date accessed: 13/03/2012
- Bulletin of the World Health Organisation – vol.84, no.10, Genebra (not web-based)
Date published: Oct. 2006
Although this information was derived from WHO, it is not completely recent. The information I used was a study on the drugs that are used as a treatment. That study was conducted throughout April 2001 and April 2005 and therefore has low validity because it is subject to era-dependence. On the other hand, the information is very reliable as it was published by WHO.
Word Count: 2987
Page count: 9
Figure 1 
Figure 2 
A child suffering from sleeping sickness is being injected with drugs. 
The percentage deaths or relapse incidences on their specific treatments. 
The risk factor ratio for deaths and relapses. OR – Odds ratio. HR – Hazard ratio. 
Fly traps for the tsetse flies.