SP Resistance Study Group

SP Resistance Study Group

The sulphadoxine-pyrimethamine (SP) resistance Study Group’s aim is to provide open access to and establish maps with the most recent data on SP resistance to inform policy decisions on the clinical effectiveness of SP when provided as part of intermittent preventive treatment of malaria in pregnancy (IPTp) or seasonal malaria chemoprevention (SMC).

Update and overview

Invitations to all known contributors will be sent out in July 2016. A first inaugural Study Group meeting will be held in Q3 2016. Data curation will remain open for all prospective contributions, and the interactive map platform enabling [online] data uploads will be available by Q4 2017. 


Malaria in pregnancy can have devastating consequences.1 The World Health Organization (WHO) currently recommends IPTp for prevention of malaria in pregnant women by administering treatment doses of an efficacious antimalarial drug during the second and third trimesters of pregnancy at predefined intervals at least a month apart. Sulphadoxine-pyrimethamine (SP) is the only antimalarial currently recommended for IPTp. However, high-level parasite resistance to SP threatens the efficacy of the strategy. In East and Southern Africa, the effectiveness of IPTp with SP to clear peripheral parasitaemia and prevent low birthweight (LBW) decreases with increasing population prevalence of the Plasmodium falciparum dihydropteroate synthase (Pf dhps) K540E mutation, which is a proxy of the quintuple dhfr/dhps mutant.2 Nevertheless, some beneficial effect on birthweight remains even in areas with high resistance (defined as >90% prevalence of Pf dhps-K540E).2, 3 However, IPTp with SP fails to inhibit parasite growth among women infected with ‘sextuple’ mutant parasites (Pf dhps-A581G in combination with the quintuple mutant),3, 4, 5, 6 defined as super-resistant parasites.7

The continued use of SP in these highly resistant areas has been a topic of recent debate, reflecting the pressing need for an effective, safe and affordable alternative to SP.6, 8, 9, 10 Meanwhile the World Health Organization (WHO), National programmes and other policy makers need information at national and sub-national levels to inform strategy decisions and help define the prevalence thresholds of certain mutations above which the IPTp-SP strategy is compromised. Ideally, these data need to be openly accessible without restrictions, in the form of user-friendly tools such as maps which show the thresholds for policy change accompanied with relevant alternative policy recommendations.

Similarly, SP is used in combination with amodiaquine (AQ) for seasonal malaria chemoprevention (SMC) in children in the Sahel regions. Population level data on molecular markers are required to obtain a better understanding of the impact of the widespread use SP-AQ for SMC on the development and spread of SP resistance, and vice versa the impact of parasite resistance on the effectiveness of SMC with this regimen. 

Aim and Objectives

The SP Resistance Study Group’s aim is to provide open access to the most recent data on SP resistance to inform policy decisions on the clinical effectiveness of intermittent preventive treatment of malaria in pregnancy (IPTp) with SP and SMC with SP-amodiaquine (AQ). Specifically, we will provide up-to-date information to WHO and WHO’s Technical Expert Group (TEG) on Drug Efficacy and Response such that germane results can be shared early with the relevant policy makers. WWARN will act as the data host and curator.

The long term goal is to establish an open access interactive map which can be accessed by policy makers and programme managers in endemic countries for national or sub-national level data to inform decisions on whether or not to switch strategy based on prevailing levels of SP resistance. The short term goal is to provide a publicly accessible database and to update the 2-dimensional surface map of SP resistance makers (dhps 437, dhps 540E and dhps 581G), and potentially a 3-D map incorporating time, to support policy-making by WHO and member states.

To achieve these important goals, we will first collate and curate data on SP resistance from all available sources into the WWARN Data Repository and update WWARN’s dhps Molecular Surveyor (http://www.wwarn.org/molecularsurveyor/), and make the data open access. An initial series of meta-analyses will be undertaken to answer key questions on the mechanisms of SP resistance and on the impact of SP resistance on the clinical effectiveness of IPTp with SP.  The final results, including the resistance maps, will be made available to WHO.

The specific objectives are:

  • Update the database and map of molecular markers of SP resistance for sub-Saharan Africa for WHO.
  • Identify the modifying effects of sulfadoxine-pyrimethamine (SP) resistance and malaria transmission intensity on the clinical effectiveness of intermittent preventive treatment of malaria in pregnancy (IPTp) with SP.
  • Determine the factors that drive the spread of SP resistance, and what can be learned from the spread of SP resistance to inform future resistance monitoring /control.
Variables for molecular data

Required for each submitted dataset:

  • Sample collection date
  • Prevalence or frequency of molecular resistance marker genotype(s)
  • Population from the samples were collected e.g. malaria patients (and if so, children, adults, pregnant women), women attending ANC or delivery, health survey participants
  • Description of the study population: age range, if patients; before treatment, day of recurrence, or day of recrudescence; if pregnant women; before or after receipt of SP during that pregnancy
  • Basic information on study site and design

Optional for each submitted dataset:

  • Patient age
  • Genotyped microsatellites in regions flanking resistance markers
  • Complexity or multiplicity of infection
Minimum required data
  • Baseline data on patient demographics
  • Alleles
  • Geo-position
  • Time
Desirable data
  • Treatment or IPTp
  • Relevant medical history including any serious and non-serious adverse events 
Data standardisation and analysis

Once uploaded into the WWARN Data Repository, datasets will be standardised according to the WWARN Clinical (and, if applicable, Pharmacology) Data Management and Statistical Analysis Plan. Data sets will be pooled into a single database of quality-assured individual patient data. 

Study Group governance and membership

The Study Group comprises investigators who contribute relevant data sets to the pooled analysis and invited technical experts. Data sets remain the property of the investigator. More details about sharing data with WWARN and how WWARN will use data are available on the WWARN website.

The Study Group collectively makes decisions with respect to including additional studies, data analysis and plans for publication, in line with the WWARN Publication Policy. Dr Cally Roperand Prof Feiko ter Kuile and Dr Jenny Hill is the Study Group Coordinator 

For further information, email Jenny Hill: Jenny.Hill@lstmed.ac.uk or clinical@wwarn.org