Proposal for an

Evidence Review Group

on MDA, MSAT and FSAT

Dr A. Bosman and Dr P. Ringwald

Malaria Policy Advisory Committee Meeting

WHO HQ Geneva, 11 September 2014

Impact of MDA, MSAT and FSAT

on malaria transmission

VECTOR

larvae

WHO 98123

HUMAN

uninfected

incubating

infective

infective

incubating

uninfected

LARVAL CONTROL

ADULT VECTOR CONTROL

DIAGNOSIS & TREATMENT MSAT & FSAT

MASS-DRUG ADMINISTRATION

CONTROL OF MAN-VECTOR CONTACT

Resilience of malaria transmission

The curves show probable growth of falciparum infection rates in epidemics

assuming primary cases at time 0 (arrow) as 0.1 per cent of the population with

falciparum infection, an incubation interval of 35 days, under the influence of

different reproduction rates for malaria. (Adapted from the Bulletin of the World

Health Organization, 1956, vol. 15:380)

Current WHO recommendations

MDA – mass treatment of all, or a large section, of the

population whether symptoms are present or not

Based on the review of results of 19 MDA projects during the

period 1932–1999 by von Seidlein and Greenwood 1 and a

Technical Consultation held in 2003 2 , WHO concluded that there

is little evidence that MDA is effective in reducing transmission

although reduction in parasite prevalence and transient reduction

in mortality and morbidity have been documented in some

cases.

1 von Seidlein L, Greenwood BM (2003). Mass administration of antimalarial drugs.

Trends in Parasitology, 19: 452–460.

2 Malaria epidemics: forecasting, prevention, early detection and control From policy to practice.

Report of a WHO Informal Consultation, 8–10 December 2003.

Current WHO recommendations

In 2010 a WHO consultation 3 reviewed the potential role

of MDA in the context of artemisinin resistance in the Greater

Mekong subregion based on evidence of impact of existing

interventions, operational and modelling considerations. The

consultation recommended immediate planning of a pilot MDA

operation in western Cambodia or eastern Thailand and the

collection of essential information on the safety and efficacy of the

candidate drugs for MDA.

3 Consideration of mass drug administration for the containment of artemisinin resistant malaria

in the Greater Mekong Subregion. Report of a WHO consensus meeting, 2010.

Current WHO recommendations

● The same consultation also reviewed the role of mass

screening and treatment (MSAT/FSAT – people in a

broad/defined geographic area are screened, regardless of

whether they have symptoms of malaria, providing treatment

for those who test positive).

● MSAT generates important information on the epidemiology of

malaria that can be useful for further containment efforts, but it

is resource-intensive and logistically challenging - lack of field-

ready, high-throughput, highly sensitive diagnostic tests.

● FSAT operationally more feasible than MSAT, this is not

delivered in all villages simultaneously, and, therefore, it is

unlikely to contribute significantly in elimination efforts.

● The contribution of MSAT and FSAT effective in reducing

transmission needs to be confirmed.

Background

● A recent systematic review 4 of 32 studies assessed MDA in

areas with different endemicity, with different medicines and

dosages, different timings and number of rounds and

concomitant implementation of vector control measures. The

review concluded that MDA appears to quickly reduce malaria

parasitaemia and several clinical outcomes, but more studies

are required to assess its impact after 6 months, the barriers

for community uptake and the potential contribution to the

development of drug resistance.

4. Poirot et al., Mass drug administration for malaria.

Cochrane Database of Systematic Reviews 2013, Issue 11.

Art. No.: CD008846. DOI: 10.1002/14651858.CD008846.pub2.

Background (continued)

● A subsequent review of the literature 5, including

unpublished studies, identified 12 MDA studies

demonstrating zero indigenous malaria cases in the

target population maintained over six months after

the end of drug administration.

● Over the last few years implementation research on MDA

and FSAT have been conducted in Cambodia , and in other

countries for which results are not yet in the public domain

(e.g. FEMSE in Comoros, MDA in Zanzibar, MSAT in Zambia

and MDA at Thai-Myanmar border). 5. UCSF Global Health Sciences. Review of mass drug

administration and primaquine use: background paper prepared for

the Bill & Melinda Gates Foundation, 2014 (unpublished document).

Impact of T3, MDA and LLINs in Anjouan Island (Comoros) Malaria reported cases: April 2010 – Dec 2013

0

50

100

150

200

250

300

Disponibilite des

données (Avril 2010 )

Formation personnelprise en charge (Juil10)

Distribution

MILD (Déc10)

Application Protocole Confirmer avant de traiter

(Juin2011)

Gratuite des

ACT

Avril2010

Gratuité TDR et formation pour utilisation( mars.11)

Affectation

Microscopistees(juil.11)

Prise en charge gratuitedes cas graves (Janv.12)

Application strict du protocole de Prise

En Charge du Paludisme (Juil.12)

Traitement de mMsse

pour l'élimination rapide

du paludisme( Oct-Nov-Déc.12)

Suivi thérapeutique. Recherche active des cas. Contrôle ded qualité des lames; Déclaration obligatoire des cas ( Janv.13)

Distribution MILD

permanet( Déc.13)

1

2

3

9

T3 MDA LLIN

1. Is there evidence of impact on malaria transmission at six month

and one year following implementation of MDA, MSAT and FSAT?

2. What are the key determinants of "durable impact" on malaria of

MDA, MSAT and FSAT?

3. What are the optimal conditions for application of MDA, MSAT and

FSAT to reduce malaria transmission in terms of endemicity levels,

combination of medicines and dosages, use of diagnostics, timings

and number of MDA rounds, concomitant deployment of vector

control interventions, IEC and pharmacovigilance?

4. What are the major limitations and challenges faced by multiple

groups in the successful application of MDA, MSAT and FSAT to

reduce malaria transmission?

ERG preliminary list of questions (1- 4)

5. What is the specific role of MDA, MSAT and FSAT in the

advanced phase of malaria elimination?

6. What is the specific role of MDA, MSAT and FSAT for the

elimination of artemisinin resistant falciparum malaria?

7. What are the main knowledge gaps and what data need to be

collected to recommend wider deployment of MDA, MSAT and

FSAT as part of initiatives to reduce malaria transmission?

8. Which of methodological aspects and ethical requirements need

to be considered by research groups and national ethical review

boards for planning and assessment of studies on the durable

impact of MDA, MSAT and FSAT on malaria transmission?

ERG preliminary list of questions (5 – 8)

Discussion points for MPAC

● Refine ERG questions to be addressed

● Systematic reviews, and recent unpublished studies

to be reviewed

● Methodological aspects and timing of ERG

(tentative: 8-10 December 2014)

● Investigators/programme managers to include as

presenters and reviewers

● Co-Chairpersons (from MPAC members) and

Rapporteurs

● AOB