Waking up to sleeping sickness'

1
Waking up to sleeping sickness.

• August Stich, Michael P. Barrett and Sanjeev
  Krishna.
• Parasitology compulsory question
• seminar.
• Presented by
• Dr. Jo Hamilton

2
Introduction.

• Re-emergence African trypanosomiasis -
  sub-Saharan countries.
• Past 30 years
• Clinical research?
• Surveillance?
• Drug development?
• Vector control?

3
The grand plan.

• Provision free anti-trypanosomal drugs.
• Development orally active trypanocidal drug.
• Attack tsetse vector.

4
What is sleeping sickness?

• Sleeping sickness (Human African Trypanosomiasis,
  HAT).
• Trypanosome protozoa.
• Trypanosoma brucei complex.
• Untreated - fatal.
• T. brucei rhodesiense weeks.
• T. brucei gambiense months.

5
Who has it and how?

• Half a million infected.
• Trypanosome transmitted - tsetse fly vector.
• Bite from infected fly.

6
An orphan disease.

• Orphan drug act?
• Struggle to retain essential drugs.
• Profit?
• HAT- destruction village communities.

7
The horror of HAT.

• Bite - infected tsetse.
• Dissemination tryps bloodstream via lymphatics.
• Waves of parasitaemia.
• Tryps immune evasion strategies.

8
The horror of HAT.

• Fever.
• Debilitation.
• Wasting.
• Blood-brain barrier.
• Sleep cycle.
• Mood, personality behaviour.
• Mutism inanition secondary infection.
• Death.

9
Questions?
10
Melarsoprol a dangerous treatment.

• Arsenical based.
• gt50 years old.
• 2nd stage T. b. rhodesiense.
• Kills 4-12.

11
Melarsoprol a dangerous treatment.

• Cardiotoxicity.
• Exfoliative dermatitis.
• Long hospital treatment.
• Costs.

12
Melarsoprol a dangerous treatment.

• Resistance.
• Rural African disease?
• Financial incentive for big pharma?
• N.B. Eflornithine.

13
Questions?
14
A glimpse of hope.

• 3 major initiatives
• Sterile tsetse release International Atomic
  Energy Agency (IAEA).
• Success in Zanzibar.
• Trapping, insecticide sterile male release.
• Logistical problems.
• Accessibility.
• Cost.

15
A glimpse of hope.

• World Health Organisation (WHO) Médecins sans
  Frontières (MSF) campaign.
• Encourage pharmaceutical companies.
• Aventis donate pentamidine, melarsoprol
  eflornithine.
• Bayer continue production suramin nifurtimox.

16
A glimpse of hope.

• Bill Melinda Gates Foundation major funding
  initiative.
• Drug development.
• DB 289 orally bioavailable diamidine pro-drug.
• Clinical trials.

17
Questions?
18
The role of science.

• 3x as much research on malaria as HAT.
• lt17 on diagnosis, treatment, control.
• gt50 malaria articles on diagnosis, treatment,
  control.
• Much research on tryps.
• Huge gap - basic research clinical need.

19
The role of science.

• Breakdown in surveillance, treatment vector
  control.
• Resurgence HAT.
• Democratic Republic of Congo, Angola Sudan.
• Destabilisation war, civil unrest.
• HIV pandemic.

20
Questions?
21
The return of sleeping sickness.

• Angola 1973 3 cases HAT.
• 2001 gt12000.
• Surveillance limited logistics safety.
• Tip of the iceberg?
• 5-10x undiagnosed.

22
Questions.
23
The future?

• Aventis, Bayer, MSF WHO 5 years drugs.
• Gates-funded initiative new drug within
  10years?
• IAEA campaign long term vector control?

24
The future?

• What if melarsoprol resistance spreads further?
• Can numbers free drugs match numbers new cases?
• What if DB 289 fails trials?
• What if sterile males tsetse release fails?
• Other efforts to combat HAT.

25
The future?

• Reformulation drugs?
• Combination chemotherapy?
• More basic information pathophysiology of HAT.
• Trials - new compounds, reformulations
  combination therapy.
• Funding agencies, health workers Ministries of
  Health involved.

26
The future?

• The ultimate battlefield is not at the bench in
  scientific laboratories or at the green table in
  urban offices.
• It is in hospitals, health centres and villages
  in the remote parts of rural Africa, often barely
  accessible by control programmes and nearly
  forgotten by the scientific community, as well as
  by politicians.

27
Questions.