HAT paper

Question 1

What is Human African Trypanosomiasis also known as?

Answer 1

Sleeping sickness

Question 2

Where is this disease found?

Answer 2

In sub saharan africa where there is appropriate habitat for its insect vector

Question 3

what is it caused by?

Answer 3

Trypanosoma brucei a protozoan parasite

Question 4

The HAT which is pathogenic to man belongs to the species T.brucei of which there are how many sub species?

Answer 4

three:
T.b.rhodesiense - acute in East and Southern africa
T.b.gambiense - chronic in west and central africa
t.b.brucei - affects domestic and wild animals not man

Question 5

What did Picozzi et al 2005 find about the geographical separation of the 2 parasites?

Answer 5

Geographical separation between t.b.gambiense and t.b.rhodesiense could soon change however, because of the continued spread of t.b.rhodesiense in Uganda towards the north west might cause an overlap in distribution of the 2 diseases.

Question 6

How many major epidemics have occurred in the last century?

Answer 6

3

Question 7

What sex and species are trypanosomes transmitted by?

Answer 7

male and female tsetse flies (Glossina spp)

Question 8

What did Vanhamme et al 2004 find about human blood plasma and trypanosomes?

Answer 8

Normal human plasma contains a trypanosome lytic factor. This factor destroys trypanosomes pathogenic for animals whereas t.b.gambiense and t.b.rhodesiense are resistant to it, each by means of a different mechanism

Question 9

Taylor et al 2006 found what about the surface coat of the parasites?

Answer 9

Trypanosomes are surrounded by a surface coat composed of a variant surface glycoprotein that protects them from lytic factors in human plasma.

Question 10

What happens when infection occurs with the surface coat of the parasites?

Answer 10

The glycoprotein on the surface of their coat is recognised by the hosts immune system which starts producing IgM and IgG antibodies. These antibodies neutralise the corresponding trypanosomes, leading to a decrease in parasitaemia. However, a few of the typanosomes will have changed their surface coats to a new variant surface glycoprotien type that is not affected by circulating antibodies, so that they can continue to proliferate until new antibodies are produced. This sequence continues, and the immune system is not able to eliminate the parasites.

Question 11

Brun 2006 discovered what about animals and reservoirs?

Answer 11

Domestic and wild animals can also become infected with T.b.g and T.b.r although they do not fall ill and play a reservoir host from which Tsetse flies can aquire the parasite

Question 12

What did Welburn et al 2001 discover about T.b.r in terms of reservoir host?

Answer 12

T.b.r is a zoonotic and usually transmitted from animal to man, where cattle are an important reservoir host

Question 13

what did Simo et al 2006 discover about T.b.g in terms of reservoir hosts?

Answer 13

T.b.g is an anthropontic and usually spread from man to man but pigs and some wild animals have been reported as being a reservoir for the parasite.

Question 14

What are the 2 stages of the disease?

Answer 14

Stage 1 = Haemolymphatic

Stage 2 = Meningoencephalitic (characterised by the invasion of CNS)

Question 15

Which disease is chronic and which disease is acute?

Answer 15

t. b.r is acute - 3 weeks

t. b.g is chronic - 3 years

Question 16

What is the one symptom which t.b.r displays in humans that t.b.g does not display?

Answer 16

Reaction at the location of the Tsetse fly bite occurs in 19% of patients.

Question 17

What did Buguet 2001 discover about the sleep disturbance symptoms?

Answer 17

Somnographic studies have shown that the disease causes dysregulation of the circadian rhythm of the sleep / wake cycle and a fragmentation of the sleeping pattern rather than the frequently reported inversion of sleep

Question 18

What are the first stage symptoms of the disease?

Answer 18

Intermittent fever, headache, pruritus

Question 19

What are the second stage symptoms of the disease?

Answer 19

Sleep disturbance, neuropsychiatric disorders

Question 20

Why do the diagnosis for the 2 parasites differ?

Answer 20

Because t.b.r the parasite load is more dense so it is easier to identify by a blood smear
and
haemoglobin and platelet counts are more frequently changed in t.b.r than in t.b.g

Question 21

How is t.b.g diagnosed and why?

Answer 21

Rely on lab examinations because the clinical features of the disease are not sufficiently specific.
Card agglutination test for trypanosomiasis developed in the late 1970s - CATT

Question 22

Explain CATT further

Answer 22

can be done on serum, capillary blood obtained from a finger prick, or blood from impregnated fliter paper

has been said that CATT does not work in some areas where an antigen is not present in the parasite

Question 23

What is the only 100% accurate way of diagnosing the disease?

Answer 23

Through identification of microscope parasites

Question 24

What did Brun 2010 say rhat present research for diagnosis focuses on?

Answer 24

1. recombinant or native trypanosome antigens that could be used to develop an improved serological test
2. methods to detect parasite antigens in blood or CSF
3. proteomic finger printing
4. low tech PCR methods
5. new blood or CSF markers for 2nd stage of disease

Question 25

Brief statement about the drug treatments

Answer 25

Few drugs are available to treat HAT and selection is based mainly on the disease stage and causative pathogen, however, all treatments can have adverse side effects

Question 26

What are the 4 drugs used to treat HAT?

Answer 26

Pentamidine
Eflornithine
Melarsoprol
Suramin

Question 27

What is pentamidine?

Answer 27

drug of choice for treatment of first stage disease caused by t.b.g
intramuscular

Question 28

what is suramin?

Answer 28

first stage t.b.r
not liked to be used for t.b.g because Onchocerca spp are also present and its high activity against these parasites can expose patients to the risk of severe allergic reactions

Question 29

what is melarsoprol?

Answer 29

used for 2nd stage of t.b.g
only choice for 2nd stage t.b.r
adverse reactions are common and can be life threatening

Question 30

what is eflornithine?

Answer 30

only new drug developed inthe last 50 years
comparing this drug with melarsoprol shows a lot less mortalities
recommonede 2nd stage t.b.g but not t.b.r because it is innately less susceptible to the drug

Question 31

are there any prevention methods?

Answer 31

there is no vaccine and chemoprophylaxis is not recommended because of the toxicity of the drugs and low risk of infection.
Only preventative measure is reduction of tsetse fly bites:
attracted to dark colours, motion of vehicles, bite through thin clothing

Question 32

Why as a result is in countries where the disease is endemic less than 0.1% of flies carry the disease?

Answer 32

because the biological cycle of HAT is very fragile becasue transmission through the tsetse fly is slow and complex