Control and elimination of onchocerciasis - uni · PDF fileControl and elimination of onchocerciasis: thresholds, breakpoints & strategies ... Hans-Peter Duerr Institute for Medical

Control and elimination of onchocerciasis:

thresholds, breakpoints & strategies

34th session of the APOC Technical Consultative Committee (TCC), Ouagadougou, 12-16 March 2012

Hans-Peter Duerr Institute for Medical Biometry

University of Tübingen, Germany

http://www.uni-tuebingen.de/modeling/Mod_Oncho_Intro_en.html

Duerr HP, University of Tübingen 2

Some reminders

• Blackflies: A strategy which has led to elimination in a certain village not necessarily will be successful at higher ABRs.

• Expectations: A strategy which works 'on average' does not work for the 'worse 50%' of cases.

• Thresholds: A critical CMFL, MF-prevalence, etc. is not independent of the ABR. Most probably only adult worms allow for formulating threshold criteria independent of the ABR.

• Time: Time cannot compensate for an insufficient strategy (insufficient coverage over 100 years will still be insufficient)

• Population size: A strategy which has been successful for a village with 100 citizens not necessarily works for a country with 100,000 citizens.


Topics • Some theory ………………………………………… • Questions & answers on CDTI:

- Which coverage? - Annual or semi-annual

treatment? - For how long? - Thresholds or criteria for successful

strategies: critical CMFL, critical ATP? • A crude classification of elimination:

ABR is in the order of thousands:

ABR is in the order of ten thousands:

ABR is in the order of hundred thousands:

Elimination by means of CDTI is possible.

Elimination by means of CDTI is difficult and

requires extra efforts.

Elimination by means of CDTI seems impossible without additional vector control.


Model & data basis of this talk

H.P. Duerr, M. Eichner / International Journal for Parasitology 40 (2010) 641–650

A: ATP dependent on ABR B: MF/mg skin snip

dependent on ATP C: MF prevalence

dependent on ATP D: MF prevalence dependent

on MF/mg skin snip E: MF ingested per fly depen-

dent on MF/mg skin snip F: L3 per fly dependent on

MF ingested per fly

The model has been cali-brated with data from various African countries, predominantly savannah areas, considering the following relationships:


Precision of predictions & Variability

H.P. Duerr, M. Eichner / International Journal for Parasitology 40 (2010) 641–650

Data often show variability of one

order of magnitude.

An 'average' ABR of 10,000

originates from ABRs observed between 3,000 and 30,000

.


The early definitions of endemicity levels

Applied on: Duerr HP et al, 2010, Int J Parasitol 40: 641–650

0

20 40

60 80

100 120

140

1 10 100 1000 10000 100000 ATP

MF

/ mg

ss

Basanez 2002 (Mexico) Basanez 2002 (Guatemala) Basanez 2002 (Cameroon) Basanez 2002 (BF, CI) Model

ATP

0

20

40

60

80

100

1 10 100 1000 10000

MF

prev

alen

ce

Basanez 2002 (Mexico) Basanez 2002 (Guatemala) Basanez 2002 (Cameroon) Basanez 2002 (BF,CI) Renz 1987 Model

0

20

40

60

80

100

0 20 40 60 80 100 120 140 MF/mg ss

MF

prev

alen

ce

Basanez 2002 (Mexico) Basanez 2002 (Guatemala) Basanez 2002 (Cameroon) Basanez 2002 (BF,CI) Model

0

1

10

100

1000

10000

1 100 10000 1000000 ABR

ATP

Garms 1983 Renz 1987 Pedersen 1985 Dietz 1982 Model

1985: OCP/GVA/85.1B 'Ten years of onchocerciasis control in West Africa', p. 12: • Hypoendemicity: ... the prevalence rate is below 40% ... the blindness rate …is generally below 1%. • Hyperendemicity: ... over 60% Onchocerca volvulus carriers in the population and an

average of more than 10-15 filariae in skin snips • Mesoendemicity: … over 40% or less than 60%, .... The definition of mesoendemicity is mainly negative:

… the disease is socially recognizable but has not yet reached a level intolerable to the community.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Persistence graph

10 100 80 60 40 30 20 400 300 200 Pre-control ATP (approximated)


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Endemic parasite burden


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… the number of adult female O. volvulus per person, averaged over the whole population.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Breakpoints


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… are parasite burdens below which an endemic state is not possible.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Endemic states

endemic


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

: these are stable states, i. e. the parasite burden has not reached an under-critical level of endemicity


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Non-endemic states

endemic

Non-endemic


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… can be reached only if the control strategy has the potential to achieve elimination (see later)


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Sub-critical transmission

endemic

Non-endemic Sub-critical


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

: transmission below the breakpoint curve is not self-sustaining, i. e. infection will die out without further interventions.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Infection-free state

endemic

Non-endemic Sub-critical In

fect

ion-

free


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… onchocerciasis is not expected to be endemic below an annual biting rate of crudely 700 bites per person per year.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Threshold biting rate TBR

endemic

Non-endemic Sub-critical In

fect

ion-

free

TBR


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… onchocerciasis is not expected to be endemic below a threshold biting rate of crudely 700 bites per person per year.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

TBR


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… onchocerciasis is not expected to be endemic below a threshold biting rate of crudely 700 bites per person per year.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Two villages

TBR


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Village A (ABR=2000)

TBR A


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… as an example of a 'hypoendemic' village.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Village B (ABR=6000)

TBR A

B


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… as an example of a 'mesoendemic' village.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

TBR A

B


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

10 years control by CDTI

TBR A

B


Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

TBR

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years

CDTI

A

B

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… CDTI from year 0 to 10.


Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

TBR

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years

CDTI No control

A

B

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… CDTI will be stopped after 10 years, and we simulate 5 years more what will happen.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Years

CDTI No control

A

B

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

… onset of control


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B

… CDTI shifts the persistence graph to the right, towards higher ABRs.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B

… for a given ABR, we can observe that the average parasite burden decreases.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B

… the TBR will soon exceed the local ABR of village A


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A

… under continuation of this strategy village A is straight on the way towards elimination.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A

The only thing what happens in village A is extinction of 'old' residual parasites.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

B

A

Termination of CDTI


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A

The persistence graph moves back towards the former location.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A

Critical for village A: the TBR comes back.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A

Critical for village A: the TBR comes back.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A

… but re-infection in village A does not occur because its parasite burden has been reduced below the breakpoint curve.


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A



0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

A

B

Elimination

After all: • Elimination

in village A


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Annual biting rate

0.1

1

0.5

0.2

10

5

3

1,000 10,000 3,000

Adu

lt fe

mal

e O

. vol

vulu

s pe

r per

son

Years

CDTI No control

B

A Elimination

Relapse

After all: • Elimination

in village A • Relapse in

village B


What is this good for?

• Elimination requires reaching a breakpoint, but…

• reaching a breakpoint is actually only a consequence of having performed CDTI to such an extent that the shifted TBR exceeds the local ABR

"Hans-Peter, this theory on adult worm stuff is nice but useless. Tell us something useful:" • Which coverage? • Annual or 6-monthly treatment? • For how long? • Thresholds or criteria for successful strategies? • Critical CMFL, critical ATP?


0 10 20 30 40 50 60 70 80 90

100

1000 10000 5000 3000 20000 40000

Coverage of CDTI required for elimination

Annual biting rate (ABR)

Min

imum

eff

icac

y of

CDT

I on

the

popu

latio

n M

F de

nsity

[%]

requ

ired

for e

limin

atio

n

Elimination

Persistence

‘Efficacy of CDTI’ depends on • number of treatment rounds per year • intra-host efficacy of ivermectin • macrofilaricidal effect of ivermectin • ABR

Macrofilaricidal effect: Under CDTI, female O. v. live on average for another…

10 years 9 years 8 years 7 years 6 years 5 years 4 years 3 years

No macro-filaricidal effect

Strong macro-filaricidal effect

HP Duerr et al. International Journal for Parasitology 41 (2011) 581–589

Note: The graph holds for very large populations; curves become more optimistic if a small popula-tion or a small transition zone is simulated.

Quantitatively relevant is the average reduction of the microfilaria density in the population which CDTI can achieve, called ‘efficacy of CDTI’ in the following.

3

4

5

6 7 8 9

10

Duerr HP, University of Tübingen 74 Time (months)

Perc

enta

ge o

f pre

trea

tmen

t M

F lo

ad (g

eom

. mea

ns)

CDTI: Annual or 6-monthly treatment? Answer: 6-monthly in most regions, for 4 reasons:

1. to reach more non-compliers improves coverage 2. to maximize the macrofilaricidal side-effect of IVM 3. to reduce the risk of resistance against IVM

(habituation of the parassite against IVM under inefficient IVM-usage) 4. to oppose the

MF-repopulation rate:

MF-repopulation starts already after 4 months

Basanez MG et al., 2008. Effect of single-dose ivermec-tin on Onchocerca volvulus: a systematic review and meta-analysis. Lancet Infectious Diseases 8: 310-322.


Annual biting rate (ABR)

Infe

ctio

n ra

te u

nder

CDT

I (%

of p

re-c

ontr

ol)

0

25

50

75

100

1000 10000 100000

MF-reduction through CDTI

60% 80% 90% 95%

With

resp

ect t

o th

e in

fect

ion

rate

CDT

I is

efficient

not efficient

CDTI: For how long? (1) TRIVIAL: at minimum over a period which covers the life-expectancy of adult O. v.

(10-14 ys, possibly less if ivermectin reduces the life-expectancy) BUT: Re-infections during control reset the clock to time zero RISKS: - Re-infection occuring under annual treatment

(see before: MF repopulation starts 4-6 months after ivermectin receipt) - Re-infections resulting from residual infection:

E. g. under annual treat-ment & an ABR of 10,000 bites per person and year: infection rate under CDTI can still be greater than 40% of the pre-control infection rate, even under very high efficay of CDTI.

HP D

uerr

et a

l. In

tern

atio

nal J

ourn

al

for P

aras

itolo

gy 4

1 (2

011)

581

–589

Note: curves become more optimistic if a small population or transition zone is simulated


0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

1

500 1000 10000 4000 2000 100000 ABR

Prev

alen

ce o

f MF

+ve

skin

snip

s

Thresholds or criteria for successful strategies? e. g. critical CMFL, critical ATP

A single value cannot be given; thresholds depend on ABR:


• A critical MF prevalence can only be expressed for ABRs up to 10000 bites per person and year.

• The critical MF prevalence underruns detection limits for ABRs greater than 10000 bites per person and year

Note: curves become more optimistic if a small population or a small transition zone is simulated

60% 80% 90% 95% efficacy of CDTI


CDTI: For how long? (2)

Not a number of years matters, but reaching the critical prevalence of carriers of adult female O. v.:


• A critical prevalence of carriers of adult female O. v. seems to be only treshold which can be expressed independent of the ABR.

• Recipe: perform CDTI until only 50% of the population still harbour adult female O.v.: then, continuing this strategy is likely to lead into elimination.

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

1

1000 500 10000 4000 2000 100000

Prev

alen

ce o

f adu

lt O

.v. +

ve

ABR

60 80 90 95% efficacy of CDTI

n o n - e n d e m i c


Hans-Peter Duerr Institute for Medical Biometry, University of Tübingen, Germany

http://www.uni-tuebingen.de/modeling/Mod_Duerr_Intro_en.html

Add Ons


Relationship MF-prevalence - CMFL

P(MF)=0.2658226+0.1419609*Log(CMFL)

Dadzie 1990 (N=11) DeSole 1991 (N=88) Whitworth 1999 (N=32)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Pre

vale

nce

with

MF-

posi

tive

skin

sni

p

0.1 1 0.8 0.5 0.3 0.2 10 8 6 5 4 3 2 100 70 50 40 30 20

CMFL(mf/s)


A crude classification scheme? ABR is in the

order of… … thousands: … ten thousands: … hundred thousands:

Elimination by means of CDTI … … is possible.

… is difficult and requires extra efforts, e. g.

6-monthly treatment

… is impossible without additional vector

control.

Corresponds precontrol values in the order of

ATP < 300 300 - 3000 > 3000

MF prevalence < 70% 70 - 85% > 85%

ABR

0

1

10

100

1000

10000

1 100 10000 1000000

ATP


0

20

40

60

80

100

1 10 100 1000 10000 ATP

MF

prev

alen

ce



Fig. 3. Qualitative illustration of the role of breakpoints and the longitudinal changes in the average densities of adult female Onchocerca volvulus (A) and microfilariae (MF per mg skin snip, (B)) in the human population. The graph is specific for a certain annual biting rate (ABR), and proportions in time and parasite burdens will change as the ABR changes. In circles: W, endemic equilibrium density of adult female parasites per host; M, endemic equilibrium MF density; BP, breakpoint; E, Elimination. Time 0–1: endemic state as found under pre-control conditions. Time = 1: onset of control: treating the population with a microfilaricide will quickly reduce the average MF density in the population (‘primary effect’ of approximately 80% in (B)), but not so the adult female parasite population (A). Time = 2: the further reduction in MF densities follows the reductions in the adult female parasite population under a control-reduced infection rate (‘secondary effect’). Ongoing infection is possible because the parasite is not eliminated. Time = 3: if long-term control by a microfilaricide is capable of bringing the adult female parasite burden below its ABR-specific breakpoint, elimination will follow (dashed line). If the breakpoint cannot be reached, parasite burdens will remain endemic at a new, control-specific equilibrium (solid line). Time 4–5: if control is stopped when the breakpoint has not been reached, parasite burdens in the population will return to their pre-control equilibrium values. H.P. Duerr et al. / International Journal for Parasitology 41 (2011) 581–589


0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

1

1000 500 10000 4000 2000 100000 ABR

0.1 0.05

1 0.5

0.2

10 5

2

20 40

1000 500 10000 4000 2000 100000 ABR

1 0.6 0.4

10 6 4

2

20

1000 500 10000 4000 2000 100000 ABR

Adul

t fem

ale

O. v

. per

per

son

MF

per m

g sk

in sn

ip

Prev

alen

ce o

f MF

+ve

skin

snip

s

C

A

D

60 80 90 95

60 80

90 95

60 80 90 95

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

1

1000 500 10000 4000 2000 100000 ABR

Prev

alen

ce o

f adu

lt O

.v. +

ve

B

60 80 90 95

Fig. 4. Density and prevalence (solid curves) of adult female Onchocerca volvulus (O. v.) and microfilariae (MF) predicted for different efficacies of community-directed treatment with ivermectin (CDTI) on the population MF density (MF per mg skin snip). The highest, black curve in each graph represents the pre-control endemicity dependent on the annual biting rate (ABR). The other four curves assume that CDTI reduces the average MF density in the population by 60%, 80%, 90% and 95%. Breakpoints are predicted for adult female O. volvulus only (dotted curves in A and B). Grey shaded areas in each graph represent the zone of non-endemic transmission. The pre-control threshold biting rate (TBR) lies at 730 bites per person per year (vertical dashed line). For MF densities in C and D, the borderline between the zone of endemic and nonendemic transmission (dashed line) decreases with both the ABR and the efficacy of control, leading to very low values for MF endemicity that are difficult to detect. In contrast, for the adult parasite burden shown in A and B the borderline between the zone of endemic and non-endemic transmission are located at higher endemicity and proceed horizontally, indicating that the status of the elimination program may be monitored independently of the ABR or the efficacy of control. The two filled circles (1 and 2) in C represent two villages to illustrate non-endemic versus endemic transmission. Breakpoints for the density and prevalence of MF are not shown because they can be misleading.

Inte

rnat

iona

l Jou

rnal

for P

aras

itolo

gy 4

1 (2

011)

581

–589


0

20 40

60 80

100 120

140

1 10 100 1000 10000 100000 ATP

MF

/ mg

ss

Basanez 2002 (Mexico) Basanez 2002 (Guatemala) Basanez 2002 (Cameroon) Basanez 2002 (BF, CI) Model

0

1

10

100

1000

10000

1 100 10000 1000000 ABR

ATP


0

20

40

60

80

100

1 10 100 1000 10000 ATP

MF

prev

alen

ce


0

20

40

60

80

100

0 20 40 60 80 100 120 140 MF/mg ss

MF

prev

alen

ce

Basanez 2002 (Mexico) Basanez 2002 (Guatemala) Basanez 2002 (Cameroon) Basanez 2002 (BF,CI) Model

0.1

1

10

100

1000

0.1 1 10 100 1000 MF/ss

MF

inge

sted

Basanez 1994 Demanou 2003 Model

0.01

0.1

1

10

0.1 1 10 100 1000 MF ingested per fly

L3 p

er fl

y

Basanez 1995 Model

Duerr HP, University of Tübingen 85 H.P. Duerr et al. / International Journal for Parasitology 41 (2011) 581–589

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