11th WHO Vector Control Advisory Group Meeting

VCAG update

Anna Bowman, VCAG Project Manager

Why evaluate new tools?

• Without evidence WHO can’t develop well informed policies

• “WHO’s legitimacy and technical authority lie in its rigorous adherence to systematic use of evidence as the basis for all policies” 12th

GPW

Evaluation Pathway for vector control products

Assess product safety, quality and efficacy

Inspect manufacturing facilities to ensure quality

Academia, developers, manufacturers and PDPs VCAG PQ

GMP and NTD with support of MPAC/STAG

Outcome

1. Consisting of staff from PQT, GMP and NTD

Pre-qualify product

(product listing)

Intervention class with WHO policy recommendation

Intervention class without WHO policy

recommendation

Submit request for

determination of pathway

Assess public health value

Assess product safety, quality and efficacy

Inspect manufacturing facilities to ensure quality

Develops policy recommendation

Pre-submission

Coordination Committee1

PH value confirmed

Safety, quality and efficacy confirmed

PH value confirmed

WHO policy recommendation

Efficacy, safety and quality confirmed

Within WHO, VCAG assesses the public health (PH) value of new intervention classes

The role of VCAG

Functions

1. To provide guidance to applicants, through WHO, on the generation of epidemiological data and study designs to enable assessment of the public health value of new vector control interventions

2. to assess the public health value of new vector interventions submitted to WHO

3. to provide advice to WHO, for submission to the Malaria Policy Advisory Committee (MPAC) and the Strategic and Technical Advisory Group for neglected tropical diseases (STAG), on the public health value of new interventions.

• Public health value is defined as: proven protective efficacy to reduce or prevent infection and/or disease in humans.

Updated VCAG Terms of Reference

• Core role to assess public health value (epi impact) of new interventions has remained the same

• The scope of VCAG has changed over time

VCAG Prequalification and VCAG

Assessment of public health value (epi studies and associated entoendpoints)

Also provided advice to product developers on topics such as:• efficacy and safety, • economic feasibility • user acceptability.

VCAG ToRs revised to focus role on assessment of public health value (epi studies and associated ento endpoints)

VCAG improvement plan

• Independent assessment of VCAG sustainability conducted by BCG (Nov 2017 – March 2018)

• Process involved consultation with 21 stakeholders and identification of areas for improvement

• Taking into account feedback WHO VCAG Secretariat developed an improvement plan that was shared at the 8th VCAG meeting in May 2018

Results from VCAG Improvement Plan

High-level achievements:

• Roles and responsibilities of WHO departments defined

• VCAG ToRs updated to clarify role of VCAG

• SoPs developed to clarify processes

• VCAG membership diversified: gene drive, regulatory and ex-industry

• Off-cycle reviews implemented, which improve timeliness

• Feedback loops improved, regularly seek input

• Communications improved: new website, updates through vector control mailing list, WebEx, transparency of interventions under review

Improvements made since May 2019

• VCAG SoPs updated to include off-cycle review processes and procedures

• Action taken based on feedback from VCAG 10 applicants (e.g. increased timing of interactions, clarified processes, etc.).

• VCAG Information sheet

• Improved processes to onboard new members and ad hoc experts • Continuing practice of VCAG 101

• Pre-calls for each working group

VCAG: next steps

• Update / revise two key documents to align with revised GMP policy-making process:• The evaluation process for

vector control products

• How to design vector control efficacy trials

VCAG portfolio overview

10Intervention

types

16 Intervention

classes

69%Planning or

conducting epi trials

38% conducting studies

11 tools for malaria (incl. 5 new nets)5 tools for Aedes-borne diseases1 tool for Leishmaniasis control

Intervention type

DescriptionIntervention

classPrototype / product

Status in WHO evaluation process

Target Disease

Insecticide-treated nets

Mosquito nets treated with chemicals either as single products or as combinations

Non-pyrethroid insecticide net

Yorkool LN (OP) Safety assessment by PQ Malaria

Pyrethroid plus non-pyrethroid insecticide net

Interceptor® G2 (pyrethroid-chlorfenapyr)

Field trial in progress Malaria

Pyrethroid plus insect growth regulator net

Royal Guard LN (pyrethroid-pyriproxifen)

Field trial in progress Malaria

Pyrethroid plus piperonylbutoxide (PBO) net*

Olyset® Plus Field trial in progress Malaria

Spatial Repellents Devices that release volatile chemicals in the air and prevent human/vector contact within the treated space

Spatial Repellents Transfluthrin passive emanator

Results from one trial shared at VCAG 10. Planning further field trials.

Malaria and dengue

Attractive Targeted Sugar Baits

Devices that attract and kill disease vectors

Attractive Targeted Sugar Bait (ATSB)

ATSB®, mosquitoes’ bait station

Field trials in planning Malaria

Peri-domestic combined repel and lure devices

Devices placed around a house and/or its surrounding (push and pull/repel and lure)

Repel and lure strategy for malaria control

The approach consists of two devices: 1) repels mosquitoes from houses and immediate surroundings (the “push”) and 2) lures mosquitoes towards odor-baited traps (the “pull”)

Concept and preliminary elements of an RCT reviewed by VCAG

Malaria

Genetic manipulation of vectors for disease control

Reduction or alteration of vector populations through genetic manipulation

Population reduction –gene-drive approach

CRISP/Cas9 - suppression construct in An. gambiae

Initial lab data reviewed by VCAG

Malaria

Population alteration –gene-drive approach

Cas9- based gene drive -anti-P. falciparum and/or anti-P. vivax constructs

Initial lab data reviewed by VCAG

Malaria

Systemic insecticides and endectocides

MDA of an endectocide to humans +/- livestock to reduce malaria transmission

Endectocides Ivermectin repurposed for malaria

Field trials in planning Malaria

Housing modification

Modification to housing to decrease exposure of inhabitants to vectors

Lethal House Lures In2Care®EaveTube with electrostatically charged coating for delivery of powder formulations

Results from one trial to be shared at VCAG 11

Malaria

Malaria-focused tools

Aedes-focused toolsIntervention

typeDescription

Intervention class

Prototype / productStatus in WHO

evaluation processTarget

Disease

Spatial Repellents Devices that release volatile chemicals in the air and prevent human/vector contact within the treated space

Spatial Repellents Transfluthrin passive emanator

Field trials in progress Malaria and dengue

Vector traps for disease management

Devices that lure and kill vectors Adulticidal oviposition and larvicidal traps

Vector traps including AGO trap, Trap-N-kill ® trap and ALO

ALO concept review May 2019

Aedes-borne viral disease

Auto-dissemination devices

In2Care® Mosquito Trap Field trials in planning Aedes-borne viral disease

Sterile insect technique (SIT) combined with microbial infection

Radiation-based sterility for mosquito population reduction and bacterial infection to prevent virus transmission

Sterile Insect Technique / Incompatible InsectTechnique

Sterilized male Ae. aegypti and Ae. albopictus infected with Wolbachia spp.

VCAG reviewed RCT protocol

Aedes-borne viral disease

Microbial control of human pathogens in adult vectors

Introduction of micro-organisms into vectors to alter target phenotypes

Wolbachia-based population alteration

wMel strain Wolbachia in Aedes aegypti

Field trial in progress Aedes-borne viral disease

Interventiontype

DescriptionIntervention

classPrototype / product

Status in WHO evaluation process

Target Disease

Systemic insecticides and endectocides

Systemic insecticide treatment of livestock to reduce or prevent transmission of pathogens transmission to humans

Systemic cattle treatment for vector control

Fipronil bolus VCAG reviewed protocol in 2017

Leishmaniasis

Leishmaniasis

At this meeting

Protocol reviews

• Spatial Repellents

• Endectocides

• Wolbachia Suppression

• PBO nets – Uganda trial (Statistical Analysis Plan)

Results from one trial

Lethal House Lures

Thank you

• Questions are welcome

• Please send feedback to vcag@who.int