1.2 Human African Trypanosomiasis (HAT)

Question 1

**1.2 Human African Trypanosomiasis (HAT) **

What should I know by the end of the lecture - this is what the exam is based on?

Answer 1

By the end of this lecture, you should be able to understand:

1. The problem caused by human African trypanosomasis in sub-Saharan Africa
2. The life cycle of the causative agent
3. Disease pathology/diagnosis/ [insect] vector control

Question 2

Human African Trypanosomiasis (HAT)

(also known as African Sleeping Sickness – stems from one of the pathologies that this disease causes)

Where is HAT present?
What population of pepole are at risk?
What is the disease associated with?
What is the percentage of prevelance in Angola. Congo and South Sudan?

Answer 2

·HAT disease is present in all 36 countries in Sub-Saharan Africa, the disease is prevalent – sometimes it is not reported but it does not mean it doesn’t exist, disease is prevalent just unreported

·60 million people at risk

·Within the regions highlighted in red highlights the number of cases – country by country there is a big wave through the centre of Africa

Question 3

What are the two types of HAT?

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Answer 3

We have different types of Trypanosoma brucei, one in the East and one in the West

Question 4

Where can the disease live in the Eastern type of HAT? What type of animals can HAT live in?
What are teh tranmission cycles for Eastern HAT? and Western HAT?

Answer 4

In the eastern part of Africa, the disease can live in animals specifically ungulate animals Eastern Africa it is zoonotic (domestic and wild animals) and anthropomorphic transmission cycles. In the Western Africa it seems to be person to person

Question 5

In terms of disease outbreaks, over the last 100 years there has been three major epidemics

What are the dates of these three epidemics?

Answer 5

Epidemics

1. 1896-1906,
2. 1920-1940,
3. late 1970’s-2000

Question 6

What are the factors that lead to a drop in screening?

1990’s

·political instability, civil unrest

·fraction of population screened

·450,000 new cases/66,000 deaths annually (1996)

2000’s

·implementation of diagnostic program & vector control

30,000 new cases (2009)

Answer 6

There is a direct correlation between monitoring populations for the presence of parasite or not, the diagram illustrates the number of reported cases (bars) the line corresponds to the population screened – when you stop screening people for the parasite the number of cases goes up

What are the factors behind the drop in screening:

• Civil unrest
• Political instability
• The screening is usually carried out by NGO. Too dangerous to send NGO staff to these places and thus not able to screen those individuals
• Into context, the last epidemic about 30 years, at its peak in the mid-1990s (about half a million new cases were taking place each year) out of that about 70/65K were dying each year because of HAT
• The political situation has improved to such an extent that the diagnostic programmes have been able to get to these regions to protect against and over the last 14 years there has been a lot of improvement
• Very few deaths – however history has shown us if we ‘don’t keep our foot on it’ it will come back, we need to come on top of the disease

Question 7

What is the insect vector of HAT?

Can both male and female transmit disease?
Why is it painful?
How many different species can transmit HAT?

Answer 7

The insect vector is the tsetse fly

Transmitted in saliva of tsetse fly (Glossina spp)

Both male & female flies can transmit disease (v. painful bite), some disease only female flies (or bugs) in this case both male and female can

Very painful to be bitten by it, ridged proboscis – saw like action without being antistasised

Approx. 34 different species can transmit HAT & these 34 can be identified and split into sub-species

Tsetse fly split into 3 groups based on

distribution, behaviour, molecular & morphology

Question 8

Tsetse fly split into 3 groups based on

1. distribution,
2. behaviour,
3. molecular & morphology

What are the 3 groups from a geographical perspective

Answer 8

For our purposes 3 groups

Different groups have different abilities to transmit different HAT forms, dependent on geographical location and environment

**1. Riverine flies **

• *2. Savannah
  3. Forest **

Question 10

**Vector Control - Female Tsetse flies are: **

**Either **

**Viviparous **

**or **

** Multivoltine **

What doesthis mean?

Answer 10

Viviparous

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· <!--[endif]-->deposits a fully developed larva

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· <!--[endif]-->burrows into the soil

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· <!--[endif]-->pupates

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· <!--[endif]-->emerges as an adult fly (month later)

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· <!--[endif]-->newly-hatched flies not infected with trypanosomes

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· <!--[endif]-->1 female fly gives birth to 1 larva that develops and goes through the various stages which emerges as one adult fly – that adult fly is not infected

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· <!--[endif]-->This gives us a chance to eradicate HAT

** Multivoltine**

· typically [believed] producing 4 generations per year, this seems like a rather long time

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· <!--[endif]-->up to 31 generations over lifespan of a female fly (subject to opinion)

Question 11

Distribution of HAT and Tsetse fly

Where is the disease found relative to the fly?

Answer 11

Wherever you have the teste fly, you have the disease

You do get sporadic cases in the West but this is because people have been to Africa

Question 12

What is the HAT parasite?

Answer 12

Trypanosoma brucei

The protozoan parasite Trypanosoma brucei major forms of parasite cause disease
Major forms of parasite: TRYPOMASTIGOTE

Question 13

The protozoan parasite Trypanosoma brucei major forms of parasite cause disease
Major forms of parasite: TRYPOMASTIGOTE

What are the characteristics of this form?

Answer 13

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· <!--[endif]-->common morphology in mammalian & insect hosts

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· <!--[endif]-->common morphology of infective forms

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· <!--[endif]-->flagellum pocket found posterior of nucleus

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· <!--[endif]-->flagellum attached to cell body by undulating membrane

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· <!--[endif]-->kinetoplast - located between nucleus and posterior end

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· <!--[endif]-->TRYPOMASTIGOTE FORM IS THE FORM LIVING IN OUR BODIES

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· <!--[endif]-->TRYPOMASTIGOTE FORM LIVING IN THE GUT OF THE INSECT

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· <!--[endif]-->TRYPOMASTIGOTE is the form being transferred from the insect to us and from us back to the insect

Question 14

How many major forms of the protozoan parasite Trypanosoma brucei are there?

Answer 14

There are four forms

1. Living in the gut of insect = procyclic trypomastigote (insect)
2. Living in mammals = bloodstream trypomastigote (mammals)

Long slender blood stream trypomastigote –roughly the same size – is highly motile - parasite looks as like its playing football with red blood cell – can divide by binary fission – cell coat is covered with a cell coat of a single protein called a variant surface glycoprotein which is keep in evading antibody mediated destruction

3. Metacyclic trypomastigote: the form that is spat out in the saliva – this is how fly can infect us (insectà humans)
4. Short stumpy trypomastigote is the form we infect the flies with

(humans àinsect) pre-adapted for life in the insect, roughly the same size have a single flagellum but the key difference between these infectious as compared to the above replicative forms is that these are unable to divide – they are pre-adapted for life in the fourth coming host

LOOK AT THE NOTES TO SEED SLIDE ON THEM

Question 15

Disease is caused by the protozoan parasite Trypanosoma brucei

What is the other major form?

Answer 15

Disease is caused by the protozoan parasite Trypanosoma brucei

Major forms of parasite: the other form is the epimastigote form – this form is found in the salivary gland of the tsetse fly

• common morphology in insect salivary gland
• flagellum pocket - located between nucleus and anterior end
• flagellum - attached to cell body for part of its length by undulating membrane
• kinetoplast - located between nucleus and anterior end

Question 16

LOOK OVER THE LIFE CYCLE IN THE LECTURE NOTES

Question 17

As a disease,

**There are two forms one associated in West Africa and the other in east Africa **

**What are these two sub-species called? **

A third form of African trypanosomiasis exists what is it called? Is it infective to humans?

Answer 17

Two sub species of T. brucei cause HAT

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· <!--[endif]-->Trypanosoma brucei gambiense ­- (West African trypanosomasis)

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· <!--[endif]-->Trypanosoma brucei rhodesiense - (East African trypanosomasis)

Third form (not infective to humans but is infective to cattle) Other African trypanosomiasis

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· <!--[endif]-->(found predominantly in ungulate mammals)

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· <!--[endif]-->Trypanosoma brucei brucei – restricted to cattle

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· <!--[endif]-->Trypanosoma vivax

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· <!--[endif]-->Trypanosoma congolense

The top two can resist our complement But the bottom one isn’t…. or so we thought, someone was working on it, in cattle

Question 18

How are the two infections distinct?

How?

Answer 18

Look up answer in notes - blue graphs

Question 19

Find it hard to suppress the parasite numbers, in this case (asymptomatic carries – rare) very low, an acute infection – from being infected to dying – evidence – takes three to four weeks

Answer 19

You have the early stage of the disease, teste fly gets the disease and you get blood infection, chancre arises at site of bite in 50%

That induced intermittent fever – once every week you have these fevers, this is because this is the immune system doing its job, as a result of the immune system trying to do its jobs (explained next week)

As the parasite invades the body, you start getting odeamas

You get a progressive degradation of health

Eventually it gets into the nervous system

As the parasite starts taking a hold in the brain it starts taking a neurological control of CNS – the person starts to change – induce a lot of naeurological conditions – sleep patterns become disturbed –
People will slip into Acoma and dye

Question 20

Diagnosis

Needs to be cheap!

Direct methods (microscopy

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• <!--[endif]-->You take a blood smear

Enrichment concentration methods,

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· <!--[endif]-->DEAE anion exchange column (RBC stay in column, parasites pass through)

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· <!--[endif]-->Microhaematocrit (capillary tubes) (buffy coat – WBC – look for parasite)

cerebrospinal fluid – look at it – diagnostic – lumber punctures

Indirect method (seriology) – looking for antibodies against the parasite in the blood

Card Agglutination Test for Trypanosomiasis (CATT test)

Take drop of blood and apply it to a card that contains fixed (dead) parasite

Answer 20

5 licensed drugs (talk about next week)

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1. <!--[endif]-->Suramin

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2. <!--[endif]-->Pentamidine

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3. <!--[endif]-->Melarsoprol

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4. <!--[endif]-->Eflornithine

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5. <!--[endif]-->NECT (nifurtimox-eflornithine combinational therapy)

Question 21

Vector Prevention and control

Answer 21

1. pre-20th century: humans did not settle or cultivate crops in areas where fly prevalent, were the fly went – they avoided it
2. Land clearing: removal of brush and woody vegetation from area Tsetse tend to rest on trunks of trees – testse fly built- you can remove some of the lands that live in
3. Slaughter of wild animals
4. Pesticide campaigns aerosol sprays (DTT) pour on formulations (cattle), spray E V E R Y T H I N G pour on the insecticide over the animal
5. Trapping – flies are attracted to a dark object
6. Irradiated males – release and try to breed out the flies, money political will, won’t work at a large geographical zone, political problems

Control efforts undertaken throughout the African continent long-term, sustainable control rarely been achieved

Tsetse control efforts tied to poverty, health, politics