Lecture 5. Flagellated Protozoa: Africa Trypanosomes 2

Question 1

What is variant surface glycoprotein (VSG)?

Answer 1

The decoy antigen
VSG covers the entire parasite surface including the flagellum of HAT
10⁶ produced per cell
The molecule is highly immunogenic
It elicits strong antibody response from the infected host
Stage-specific

Question 2

What is the parasite able to do with VSG?

Answer 2

The parasite is able to switch VSG expression (when the immune system starts to recognise the antigen)
There are&raquo_space;200 VSG genes, these are under transcriptional control

Question 3

What does expression switching result in?

Answer 3

Undulating fever which can last for months
Parasites from each peak of infection are antigenically distinct

Question 4

How is HAT diagnosed?

Answer 4

Through symptomatic, systematic and passive screening

Question 5

What are examples of the screenings uses to diagnose HAT?

Answer 5

Serological test: card agglutination test (CATT) for T. b. gambiense only
Rapid serological tests
Microscopy

Question 6

How can the stage of HAT be diagnosed?

Answer 6

On clinical or serological positive evidence
Diagnosis of the stage of disease is a necessary step to identify the appropriate treatment
Inspection of CSF obtained by lumber puncture to define disease stage
Trypanosomes (or high WBC count) demonstrated in CSF indicates 2nd stage disease

Question 7

How many drugs are there for treatment of HAT?

Answer 7

Very few licensed drugs despite recent progress

Question 8

What are all HAT licensed drugs?

Answer 8

Sub-species specific

Question 9

What is the only HAT drug that is effective against both late stage HATs?

Answer 9

Melarsoprol

Question 10

What is the problem with taking melrasoprol?

Answer 10

Melarsoprol is toxic (arsenic based drug - kills 5-10% people treated)
Resistance to melarosprol has been observed in field

Question 11

What is eflornithine and why is it not used often?

Answer 11

Effective against late stage T. b. gambiense, very expensive

Question 12

What is fexinidazole?

Answer 12

New orla therapy to treat both stages of T. b. gambiense HAT, rapid approval given in DRC where 85% HAT is found

Question 13

How is T. b. gambiense HAT controlled?

Answer 13

To reduce person to person transmission
Active or passive case detection and treatment (major component of control)
Vector control plays little to no part of control (low cost-effectiveness)
Large scale epidemics in 20th century controlled by 1960s by active case detection and treatment programmes

Question 14

How is T. b. rhodesiensese HAT controlled?

Answer 14

To reduce transmission from zoonotic reservoirs
Vector control is central (animal reservoirs require vector control)
Cattle treatment becoming more common (Uganda)
Case screening conducted for humanitarian reasons

Question 15

How does vector control reduce disease?

Answer 15

Prevents initial infection

Question 16

How does case treatment reduce disease?

Answer 16

Reduces circulation of parasites

Question 17

How can tsetse flies be controlled?

Answer 17

Tsetse flies have a low reproductive potential (approx 8 offspring per 10 day cycle)
Therefore killing 4% of the females per day should cause specie extinction

Question 18

What are examples of insecticide applications used to control tsetse flies?

Answer 18

Traps/targets e.g tiny target traps
Dips or ‘Pour-on’ topical treatment for cattle e.g RAP
Ultra-low volume (ULV) spraying (not used any more as both costly and damaging)
Sterile Insect Technique

Question 19

What are examples of standard tsetse traps?

Answer 19

Electrified black target with flanking net
Blue biconical trap with flaking electrified grid
(Tsetse flies are attracted to colours like blue and black)
Surround villages at intermittent distances (probably cant be done on a large scale)

Question 20

How was the tsetse fly population in Zanzibar eradicated (Glossina austeni) through the use of sterile insect technique? (SIT)?

Answer 20

1988 tsetse population suppressed using insecticide-treated cattle & traps
Serial release of sterilised males by aircraft, 60,000 per week in 1-2km flight lines
1994-1997 >8.5 million males released
1995 sterile : indigenous male ratio >100:1; >70% barren females
1996-7 Tsetse population crash; Glossina austeni eradicated

Question 21

How much did it cost to use SIT in Zanzibar?

Answer 21

$8 million

Question 22

Could SIT work elsewhere?

Answer 22

No
Would require $67 billion and 350,000 years to eradicate 22 species

Question 23

Between 1999-2010, how many cases were there of T. b. gambiense and rhodesiense?

Answer 23

75% less of each
T. b. gambiense fell from 27,862 to 6,984 while T. b. rhodesiense fell from 619 to 155
>40% of endemic countries report fewer than 20 cases per year but under-reporting ratio 3:1 (2015) from 10:1 (1990s) suggesting 21,000 new cases per year

Question 24

What was the treatment progress of HAT between 2010-15 in 36 endemic countries?

Answer 24

Reduced number of reported cases <3,000 (2015) compared to 10,000 (2009)
Enhanced support for surveillance now defined by accurate maps
Lowest reported incidence for 75 years

Question 25

How was the incidence of HAT reduced between 2010-15?

Answer 25

Active surveillance of defined high-risk foci
Donation of pentamidine, nifurtimox
Donation of eflornithine against chronic HAT

Question 26

What are the current elimination targets of HAT?

Answer 26

Eliminate HAT by 2030; and in selected countries of low incidence by 2020

Question 27

How will the current elimination targets of HAT be met?

Answer 27

Scale up “tiny insecticide impregnated targets”
New improved diagnostic tests
Utilise new drug fexinidazole
Chemotherapy/RAP for cattle against acute disease in Uganda

Question 28

What is the current situation with HAT in Africa?

Answer 28

Control seems to be working in many places, with active foci being generally well known and reducing in size
Political instability in some regions, reduced monitoring = may hide scale of the problem
Most important areas of disease burden in DRC with 85% of transmission

Question 29

When do current model projections estimate HAT eradication?

Answer 29

2059-92