PERSPECTIVE

Monitoring parasite diversityfor malaria elimination insub-Saharan AfricaAnita Ghansah,1 Lucas Amenga-Etego,2 Alfred Amambua-Ngwa,3 Ben Andagalu,4

Tobias Apinjoh,5 Marielle Bouyou-Akotet,6 Victoria Cornelius,7 Lemu Golassa,8

Voahangy Hanitriniaina Andrianaranjaka,9 Deus Ishengoma,10 Kimberly Johnson,7

Edwin Kamau,4 Oumou Maïga-Ascofaré,12,13 Dieudonne Mumba,11 Paulina Tindana,2

Antoinette Tshefu-Kitoto,11 Milijaona Randrianarivelojosia,9 Yavo William,14

Dominic P. Kwiatkowski,7,15 Abdoulaye A. Djimde12,15*

The African continent continues to bear the greatest burden of malaria and the greatestdiversity of parasites, mosquito vectors, and human victims. The evolutionary plasticity ofmalaria parasites and their vectors is a major obstacle to eliminating the disease. Of currentconcern is the recently reported emergence of resistance to the front-line drug, artemisinin, inSouth-East Asia in Plasmodium falciparum, which calls for preemptive surveillance of the Africanparasite population for genetic markers of emerging drug resistance. Here we describe thePlasmodium Diversity Network Africa (PDNA), which has been established across 11 countriesin sub-Saharan Africa to ensure that African scientists are enabled to work together and toplay a key role in the global effort for tracking and responding to this public health threat.

Africa is home to the most successful malariavector (Anopheles gambiae complex) andthe deadliest malaria parasite (Plasmodiumfalciparum). Despite efforts to eradicate ma-laria in the 1950s and early 1960s, 207million

cases and 627,000 malaria deaths were estimatedto have occurred in 2012, mostly in sub-SaharanAfrica and in children under 5 years of age (1). Theinability to eradicate malaria reflects the complexcoevolution of the three eukaryotic genomes in-volved and represents the major biological chal-lenge to vaccine and drug development. Sincepublication of the full genome of a reference clone,many other model and population isolates havebeen sequenced (2), which has provided someinsight into the genetic variation responsible forphenotypes like drug resistance and virulence.

However, the global genome-wide pattern ofgenetic diversity across most endemic regions ispoorly understood, as few natural Plasmodiumfalciparum populations have been analyzed.Malaria elimination efforts in Africa are heavily

reliant on artemisinin combination therapies (ACT)yet no coordinated effort for monitoring emer-gence or prevention of the spread of artemisininresistance is in place in Africa. In addition, intro-duction of new malaria vaccines or mass ther-apeutic approaches to control and eliminationwill increase selection for resistance in parasitepopulations that could damage the effectivenessof these and future tools (Fig. 1).

Rationale and mission for an AfricanPlasmodium Diversity NetworkThe emergence of antimalarial resistance to ar-temisinin in Southeast Asia (3, 4) calls for globalmonitoring of the parasite population (5). TheMalariaGEN community has already built a suc-cessful framework for data-sharing (6); hence, wehave adopted this model to form the PlasmodiumDiversity Network Africa (PDNA). The concept ofPDNA was seeded by several African scientistsduring the Genomic Epidemiology of Malariaconference at Hinxton, United Kingdom, in 2012.In May 2013, the network was formally launchedin Accra, Ghana, when scientists and clinical re-searchers met from 13 research groups from acrossAfrica (Fig. 2).The mission of PDNA is to explore the malar-

ia parasite’s genetic and phenotypic diversity toadvance the malaria elimination and eradicationagenda in sub-Saharan Africa. We have initiatedor will initiate projects to investigate Plasmodiumpopulation structure and evolution, to survey thefrequencies of current and novel molecular markersof antimalarial drug resistance, and specifically tomonitor the emergence and spread of artemisininresistance in sub-Saharan Africa.

How will PDNA contribute tomalaria elimination?

To succeed, malaria elimination requires knowl-edge of parasite genome variation in differentgeographical locations and of recent evolutionaryselection and a better understanding of the fac-tors that determine gene flow between locations,such as rates of inbreeding and population struc-ture. The PDNAmembership represents the rangeof malaria diversity in Africa. The Network is inits infancy and is bound to evolve with time. EachPDNA member brings specific scientific expertise(table S1) and the capacity to collect local biolog-ical material, as well as clinical data. PlasmodiumDNA will be either analyzed on site or dispatched

SCIENCE sciencemag.org 12 SEPTEMBER 2014 • VOL 345 ISSUE 6202 1297

1Noguchi Memorial Institute for Medical Research, Accra,Ghana. 2Navrongo Health Research Centre, Navrongo,Ghana. 3Medical Research Council, Gambia Unit, Banjul, TheGambia. 4KEMRI/United States Army Medical ResearchUnit–Kenya, Kisumu, Nairobi, Kenya. 5Department ofBiochemistry and Molecular Biology, University of Buea,Buea, Cameroon. 6Department of Parasitology Mycology,Faculty of Medicine, Université des Sciences de la Sante,Libreville, Gabon. 7MRC Centre for Genomics and GlobalHealth, University of Oxford, Oxford, UK. 8Aklilu LemmaInstitute of Pathobiology, Addis Ababa University andArmauer Hansen Research Institute, Addis Ababa, Ethiopia.9Malaria Research Unit, Institut Pasteur de Madagascar,Antananarivo, Madagascar. 10National Institute for MedicalResearch, Tanga, Tanzania. 11Institut National de RechercheBiomédicale, Ecole de Santé Publique/Faculté de Médecine/Université de Kinshasa, Kinshasa, Democratic Republic of theCongo. 12Malaria Research and Training Centre (MRTC),Department of Epidemiology of Parasitic Diseases, Faculty ofPharmacy, University of Sciences, Techniques andTechnologies of Bamako, Bamako, Mali. 13Bernhard NochtInstitute for Tropical Medicine in Hamburg, Germany.14Malaria Research and Control Center, National Institute ofPublic Health, Abidjan, Ivory Coast. 15Wellcome Trust SangerInstitute, Hinxton, UK.*Corresponding author. E-mail: adjimde@icermali.org

Fig. 1. Queuing for malaria diagnosis in Kisumu County, Kenya. [Photo credit: Hoseah M. Akala,Kenya Medical Research Institute/U.S. Army Medical Research Unit—Kenya]

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to various laboratories, such as the Wellcome TrustSanger Institute, UK, for sequencing, genotyping,and various wet laboratory investigations to surveyfor evidence of evolution in response to recent orongoing elimination measures. PDNA studies willtranslate genomics data on Plasmodium diversityinto evidence to be shared with the sub-SaharanMinistries of Health; national malaria control pro-grams; regional and international health author-ities, such as the Africa Bureau of the World HealthOrganization (WHO) and the WHO global malariaprogram; and other stakeholders (Fig. 3).Pooled analysis of data will provide larger

sample size and comparable information acrossthe African continent, as well as the detection ofrarer genetic events, site-specific issues, and oppor-tunities for modelling. Hence, PDNA will havean Africa-wide dynamic view of malaria diversityand recent evolution. Through real-time knowledge-sharing and dissemination, lessons learned willbe openly available to the various stakeholders.

Current projects

Each study site will adopt common protocols; com-mon standard operating procedures; and, when-ever possible, the same reagents and supplies. Forexample, using seed funding from the UKMedicalResearch Council, we have initiated a baseline inves-tigation of P. falciparum diversity in sub-Saharan

Africa. Each site collected 100 leukocyte-depletedP. falciparum–infected blood samples. DNA wasextracted and shipped to the Wellcome TrustSanger Institute for whole-genome sequencing,and data analysis is under way with support fromthe MalariaGEN resource center. As the new K13propeller polymorphisms have been described asa molecular marker for artemisinin resistance(7), we have also been investigating their presenceand prevalence in each of our African sites. Withinweeks, each PDNA site collected, processed, andshipped genomic DNA or dried blood spots forsequencing. Together, these projects show howa coordinated network of African scientists canmount a rapid surveillance response.The institutions involved in PDNA are at dif-

ferent levels of scientific expertise, and hence, apriority will be to engage in training and capacity-development at each participating institution forknow-how as well as ethics. Although the primaryfocus of the PDNA project is Plasmodium, the pro-cess of obtaining parasite DNA involves the col-lection of blood samples from human volunteers.Thus, in accordance with international ethicalguidelines, voluntary informed consent of re-search participants is sought in each of theprojects, and all PDNA research proposals aresubmitted to relevant ethics committees for re-view and approval.

Conclusion

The PDNA represents an African initiative for theassessment of endemic-country malaria parasitediversity at the genotype and phenotype levels toaddress scientific questions most relevant to thesuccessful elimination of malaria in sub-SaharanAfrica. PDNA will use its range of scientific, geo-graphic, epidemiologic, political and ethno-linguisticdiversity to engage local and international stake-holders, including health policy decision-makers,to ensure that we contribute directly to the globalagenda for malaria elimination.

REFERENCES AND NOTES

1. WHO, World Malaria Report (WHO, Geneva, 2013)2. M. J. Gardner et al., Nature 419, 498–511 (2002).3. H. Noedl et al., Clin. Infect. Dis. 51, e82–e89 (2010).4. A. M. Dondorp et al., N. Engl. J. Med. 361, 455–467 (2009).5. R. M. Fairhurst et al., Am. J. Trop. Med. Hyg. 87, 231–241(2012).

6. Malaria Genomic Epidemiology Network, Nature 456, 732–737(2008).

7. F. Ariey et al., Nature 505, 50–55 (2014).

ACKNOWLEDGMENTS

Seed funding and support was obtained from MedicalResearch Council UK (G0600718). We thank R. Giacomantonio forhelp with Fig. 1.

SUPPLEMENTARY MATERIALS

www.sciencemag.org/content/345/6202/1297/suppl/DC1Table S1References

31 July 2014; accepted 8 August 201410.1126/science.1259423

1298 12 SEPTEMBER 2014 • VOL 345 ISSUE 6202 sciencemag.org SCIENCE

Madagascar

Mali

Cameroon

Gabon DRCLibreville

Map by Free Vector Maps, http://freevectormaps.com

BueaGhanaCôte d’Ivoire

The Gambia

Tanzania

Addis Ababa

NairobiKenya

Ethiopia

Tanga

BamakoBanjul

Accra

Navrongo

Abidjan

Antananarivo

Kinshasa

Countries represented by the Plasmodium Diversity Network Africa members

Fig. 2. Countries represented by the Plasmodium Diversity Network Africa members.

Parasites, epidemiology, phenotypes

Sequencing, informatics and biostatistics

Population genomic variation

Genetic selection from interventions

New evidence:•Emergence and spread of drug/vaccine resistance

•Intervention efficacy•Intervention failure

MOH

Enabling processes

Data and training

Policy

PDNA

Fig. 3. Flow diagram of how PDNA will contrib-ute to malaria elimination policy decisions.

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Monitoring parasite diversity for malaria elimination in sub-Saharan Africa

Randrianarivelojosia, Yavo William, Dominic P. Kwiatkowski and Abdoulaye A. DjimdeKamau, Oumou Maïga-Ascofaré, Dieudonne Mumba, Paulina Tindana, Antoinette Tshefu-Kitoto, MilijaonaVictoria Cornelius, Lemu Golassa, Voahangy Hanitriniaina Andrianaranjaka, Deus Ishengoma, Kimberly Johnson, Edwin Anita Ghansah, Lucas Amenga-Etego, Alfred Amambua-Ngwa, Ben Andagalu, Tobias Apinjoh, Marielle Bouyou-Akotet,

DOI: 10.1126/science.1259423 (6202), 1297-1298.345Science 

ARTICLE TOOLS http://science.sciencemag.org/content/345/6202/1297

MATERIALSSUPPLEMENTARY http://science.sciencemag.org/content/suppl/2014/09/11/345.6202.1297.DC1

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