The Anders Björkman Malaria Project - Malaria treatment and control

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The malaria research group - The main focus of Anders Björkmans malaria group is malaria treatment and control.

The Malaria Research Group was established in 1980 and is presently part of the Department of Microbiology , Tumor and Cell Biology at the Karolinska Institutet , Stockholm.

Between 1980 and 2000 the three main areas of research were malaria control, chemotherapy and immunity. After 2000 the research has focused on novel malaria elimination tools and control strategies and the evolution of resistance to new antimalarial drugs.

Comprehensive collaborations have over the years developed with institutions in several endemic countries, initially in Liberia and thereafter mainly in Tanzania including a major project in Zanzibar that has been running since 2002. Other presently ongoing collaborations include projects in Mali and Guinea Bissau.

Over the years our malaria research has resulted in more than 300 publications in international journals and 31 PhD theses completed by students from 12 different countries.

 

 

Group members

Professor, senior

Anders Björkman

Phone: +46-(0)8-524 868 29
Organizational unit: Anders Björkman group
E-mail: Anders.Bjorkman@ki.se

Associated

Berit Schmidt

Phone: +46-(0)8-524 868 05
E-mail: berit.schmidt@ki.se

Associated

Johan Ursing

E-mail: Johan.Ursing@ki.se

Postdoc

Irina Tatiana Jovel Quiñonez Dalmau

Organizational unit: Anders Björkman group
E-mail: irina.jovel@ki.se

Postdoc

Ulrika Morris

Organizational unit: Anders Björkman group
E-mail: ulrika.morris@ki.se

Assistant professor

Andreas Mårtensson

Organizational unit: Anders Björkman group
E-mail: Andreas.Martensson@ki.se

Graduate Student

Peter Olumese

Organizational unit: Anders Björkman group
E-mail: Peter.Olumese@ki.se

Research assistant

Atiqul Islam

E-mail: atiqul.islam@ki.se

Associated

Juliana Inoue

E-mail: juliana.inoue@ki.se

 


Projects

The main present malaria projects in the malaria research unit at Karolinska Institutet include new strategies for malaria elimination and anti-malarial treatments, evolution of drug resistance, and new tools and strategies for malaria diagnosis. Follow the links to find out more about each project.

New strategies for malaria control - aiming at elimination in Zanzibar

Zanzibar was first in Sub-Saharan Africa to implement new modern partly novel malaria control/elimination methods on a wide scale, including tools such as rapid malaria diagnostic tests, artemisinin-based combination therapies, insecticide-treated bed nets and indoor residual spraying. Our Zanzibar project has therefore developed into a model pilot project for modern control/elimination interventions in endemic malaria situations commonly found in Sub-Saharan Africa.

Our results have shown a unique massive decrease in malaria transmission and public health burden (reduced morbidity and mortality), creating hope for the potential elimination of malaria on the isles of Zanzibar and the African continent. Our present aim is to provide historical evidence and proof of concept for possible malaria elimination from a high endemic area.

Specific studies focus on new targeted elimination strategies, are now being undertaken to develop novel methods for malaria incidence surveillance and, drug resistance monitoring, and understanding as well as ensuring the sustainability of intervention usage and community uptake. The implications of successful malaria elimination control on the socio-economic development of Zanzibar will also be studied.

 

Modern artemisinin-based combination drugs against malaria - malaria drugs and evolution of resistance

The global strategy for malaria control/elimination relies on sustained high efficacy of artemisinin-based combination therapies (ACT) as an anti-malarial treatment. The high efficacy of ACTs relies on the fast acting artemisinin component together with the long acting partner drugs. The emergence of resistance to ACTs poses one of the largest challenges in malaria control and elimination.

We employ in vivo and in vitro methods to study the selection of resistant parasite populations following drug exposures. Genetic markers of malaria parasite tolerance and resistance to antimalarial drugs are a useful tool for the surveillance of antimalarial drug resistance. We monitor molecular markers to track the spread of resistance alleles in parasite populations over time. Specific attention is given to the artemisinin family of compounds as well as their partner drugs included in the recommended combination therapies.

 

New tools and strategies for malaria diagnosis

In the era of decreasing malaria incidence there are needs for more sensitive and effective diagnostic tools. Rapid diagnostic tests (RDTs) is an efficient diagnostic tool for malaria diagnosis in field health facilities, however in low endemic/ pre-elimination areas where a majority of parasite carriers are asymptomatic, the parasite densities are often too low to be detected by RDTs. Molecular technologies like Loop mediated Isothermal Amplification (LAMP) and PCRs are assessed as future tools for diagnosis and surveillance purposes and have been evaluated in several field studies. One of our studies have also focused on the aetiology of non-malarial, microbial manifestations of childhood fever and the efficiency of Integrated Management of Childhood Illness (IMCI) algorithms for optimal management of fever patients.

Collaborations

The Anders Björkman Malaria Group has several collaborations in many parts of the world, the most extensive are:

  • Zanzibar Malaria Control Program, Zanzibar Ministry of Health and Social Welfare, Tanzania
  • Muhimbili University for Health and Allied Sciences, Dar es Salaam, Tanzania
  • Malaria Research and Training Center, University of Bamako, Mali
  • Univesidad Nacional Autonoma de Honduras (UNAH), Tegucigalpa, Honduras
  • The Bandim Health Project, Guinea-Bissau

Malaria facts

Malaria is curable
There are approx 250 million cases of malaria each year
Malaria causes approx 1 million deaths each year
3,3 billion people live in areas of malaria transmission
Malaria costs are estimated to be 12 billion USD per year in Africa alone

Risk Groups

Children under the age of five and pregnant women are most at risk of severe malaria. People living in highly endemic areas develop partial resistance to malaria over time. Children under the age of five, who have not yet had time to develop partial immunity, account for 85% of all deaths from malaria. Pregnant women are also more susceptible due to parasite invasion of the placenta.

Symtoms

The symptoms of malaria are fever, headache, muscle/joint pain and fatigue. If the disease is not cured it will lead to severe malaria, which if left untreated may be lethal.

The malaria parasite

The malaria parasite has a complicated lifecycle with important stages in both mosquitoes and humans.

Malaria is caused by a unicellular parasite of the genus Plasmodium, and is transmitted by the female Anopheles mosquito that bites primarily from dusk to dawn.

In brief, parasites are transmitted to humans in the saliva of the mosquito when the mosquito takes a blood meal. First the parasites invade liver cells and thereafter red blood cells, where the parasites multiply million-fold.

These red blood cells eventually burst releasing the parasites into the blood stream for re-invasion of new red blood cells. This occurs at 46 or 72 hour intervals (depending on the parasite species) resulting in the symptoms of recurrent fever peaks typical of malaria.

 

Malaria cure

There is a cure for malaria, thanks to efficient antimalarials such as the new artemisinin-based combination therapies.

However, accurate diagnosis and prevention of transmission are equally important in modern malaria control. Methods of prevention include sleeping under insecticide impregnated mosquito nets and indoor spraying with insecticides.

Chemoprophylaxis may also be used by visitors to malaria endemic areas.

More info

For more information about malaria, please visit the WHO malaria website.

WHO - 10 facts on malaria

Publications

2017

Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings.
Hopkins H, Bruxvoort K, Cairns M, Chandler C, Leurent B, Ansah E, et al
BMJ 2017 Mar;356():j1054

Unexpected selections of Plasmodium falciparum polymorphisms in previously treatment-naïve areas after monthly presumptive administration of three different anti-malarial drugs in Liberia 1976-78.
Jovel I, Björkman A, Roper C, Mårtensson A, Ursing J
Malar. J. 2017 Mar;16(1):113

Field Evaluation of a High Throughput Loop Mediated Isothermal Amplification Test for the Detection of Asymptomatic Plasmodium Infections in Zanzibar.
Aydin-Schmidt B, Morris U, Ding X, Jovel I, Msellem M, Bergman D, et al
PLoS ONE 2017 ;12(1):e0169037

2016

Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial.
Mwaiswelo R, Ngasala B, Jovel I, Aydin-Schmidt B, Gosling R, Premji Z, et al
Malar. J. 2016 Aug;15(1):435

Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.
Mwaiswelo R, Ngasala B, Jovel I, Gosling R, Premji Z, Poirot E, et al
Malar. J. 2016 Jun;15():316

Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies.
Mita T, Culleton R, Takahashi N, Nakamura M, Tsukahara T, Hunja C, et al
Antimicrob. Agents Chemother. 2016 Jun;60(6):3340-7

Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar - Aetiologies, Antibiotic Treatment and Outcome.
Elfving K, Shakely D, Andersson M, Baltzell K, Ali A, Bachelard M, et al
PLoS ONE 2016 ;11(1):e0146054

A deep sequencing tool for partitioning clearance rates following antimalarial treatment in polyclonal infections.
Mideo N, Bailey J, Hathaway N, Ngasala B, Saunders D, Lon C, et al
Evol Med Public Health 2016 Jan;2016(1):21-36

2015

Safety and efficacy of re-treatments with pyronaridine-artesunate in African patients with malaria: a substudy of the WANECAM randomised trial.
Sagara I, Beavogui A, Zongo I, Soulama I, Borghini-Fuhrer I, Fofana B, et al
Lancet Infect Dis 2016 Feb;16(2):189-98

Field deployment of loop-mediated isothermal amplification for centralized mass-screening of asymptomatic malaria in Zanzibar: a pre-elimination setting.
Morris U, Khamis M, Aydin-Schmidt B, Abass A, Msellem M, Nassor M, et al
Malar. J. 2015 May;14():205

Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali.
Ouattara A, Kone A, Adams M, Fofana B, Maiga A, Hampton S, et al
Am. J. Trop. Med. Hyg. 2015 Jun;92(6):1202-6

Characterising temporal trends in asymptomatic Plasmodium infections and transporter polymorphisms during transition from high to low transmission in Zanzibar, 2005-2013.
Morris U, Xu W, Msellem M, Schwartz A, Abass A, Shakely D, et al
Infect. Genet. Evol. 2015 Jul;33():110-7

SYBR Green real-time PCR-RFLP assay targeting the plasmodium cytochrome B gene--a highly sensitive molecular tool for malaria parasite detection and species determination.
Xu W, Morris U, Aydin-Schmidt B, Msellem M, Shakely D, Petzold M, et al
PLoS ONE 2015 ;10(3):e0120210

Loop-mediated isothermal amplification (LAMP) for point-of-care detection of asymptomatic low-density malaria parasite carriers in Zanzibar.
Cook J, Aydin-Schmidt B, González I, Bell D, Edlund E, Nassor M, et al
Malar. J. 2015 Jan;14():43

2014

Mass screening and treatment on the basis of results of a Plasmodium falciparum-specific rapid diagnostic test did not reduce malaria incidence in Zanzibar.
Cook J, Xu W, Msellem M, Vonk M, Bergström B, Gosling R, et al
J. Infect. Dis. 2015 May;211(9):1476-83

Epidemiology of malaria in a village in the Rufiji River Delta, Tanzania: declining transmission over 25 years revealed by different parasitological metrics.
Färnert A, Yman V, Homann M, Wandell G, Mhoja L, Johansson M, et al
Malar. J. 2014 Nov;13():459

Loop mediated isothermal amplification (LAMP) accurately detects malaria DNA from filter paper blood samples of low density parasitaemias.
Aydin-Schmidt B, Xu W, González I, Polley S, Bell D, Shakely D, et al
PLoS ONE 2014 ;9(8):e103905

Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.
Venkatesan M, Gadalla N, Stepniewska K, Dahal P, Nsanzabana C, Moriera C, et al
Am. J. Trop. Med. Hyg. 2014 Oct;91(4):833-43

Single nucleotide polymorphisms in Plasmodium falciparum V type H(+) pyrophosphatase gene (pfvp2) and their associations with pfcrt and pfmdr1 polymorphisms.
Jovel I, Ferreira P, Veiga M, Malmberg M, Mårtensson A, Kaneko A, et al
Infect. Genet. Evol. 2014 Jun;24():111-5

2012

Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA5.
Tanabe K, Arisue N, Palacpac N, Yagi M, Tougan T, Honma H, et al
Vaccine 2012 Feb;30(9):1583-93

Comparing changes in haematologic parameters occurring in patients included in randomized controlled trials of artesunate-amodiaquine vs single and combination treatments of uncomplicated falciparum in sub-Saharan Africa.
Zwang J, Ndiaye J, Djimdé A, Dorsey G, Mårtensson A, Karema C, et al
Malar. J. 2012 Jan;11():25

Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands.
Cavaco I, Piedade R, Msellem M, Bjorkman A, Gil J
Trop. Med. Int. Health 2012 Jul;17(7):854-7

Artemether-lumefantrine treatment failure despite adequate lumefantrine day 7 concentration in a traveller with Plasmodium falciparum malaria after returning from Tanzania.
Färnert A, Ursing J, Tolfvenstam T, Rono J, Karlsson L, Sparrelid E, et al
Malar. J. 2012 May;11():176

pfmdr1 amplification is related to increased Plasmodium falciparum in vitro sensitivity to the bisquinoline piperaquine.
Veiga M, Ferreira P, Malmberg M, Jörnhagen L, Björkman A, Nosten F, et al
Antimicrob. Agents Chemother. 2012 Jul;56(7):3615-9

Clinical tolerability of artesunate-amodiaquine versus comparator treatments for uncomplicated falciparum malaria: an individual-patient analysis of eight randomized controlled trials in sub-Saharan Africa.
Zwang J, Dorsey G, Djimdé A, Karema C, Mårtensson A, Ndiaye J, et al
Malar. J. 2012 Aug;11():260

A qualitative study on caretakers' perceived need of bed-nets after reduced malaria transmission in Zanzibar, Tanzania.
Beer N, Ali A, Eskilsson H, Jansson A, Abdul-Kadir F, Rotllant-Estelrich G, et al
BMC Public Health 2012 Aug;12():606

Decreased prevalence of Plasmodium falciparum resistance markers to amodiaquine despite its wide scale use as ACT partner drug in Zanzibar.
Fröberg G, Jörnhagen L, Morris U, Shakely D, Msellem M, Gil J, et al
Malar. J. 2012 Sep;11():321

Quinine treatment selects the pfnhe-1 ms4760-1 polymorphism in Malian patients with Falciparum malaria.
Kone A, Mu J, Maiga H, Beavogui A, Yattara O, Sagara I, et al
J. Infect. Dis. 2013 Feb;207(3):520-7

Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Honduras.
Lopez A, Ortiz A, Coello J, Sosa-Ochoa W, Torres R, Banegas E, et al
Malar. J. 2012 Nov;11():391

CYP2C8 status of patients with malaria influences selection of Plasmodium falciparum pfmdr1 alleles after amodiaquine-artesunate treatment.
Cavaco I, Mårtensson A, Fröberg G, Msellem M, Björkman A, Gil J
J. Infect. Dis. 2013 Feb;207(4):687-8

Assessing the cost-benefit effect of a Plasmodium falciparum drug resistance mutation on parasite growth in vitro.
Fröberg G, Ferreira P, Mårtensson A, Ali A, Björkman A, Gil J
Antimicrob. Agents Chemother. 2013 Feb;57(2):887-92

Prevalence of PCR detectable malaria infection among febrile patients with a negative Plasmodium falciparum specific rapid diagnostic test in Zanzibar.
Baltzell K, Shakely D, Hsiang M, Kemere J, Ali A, Björkman A, et al
Am. J. Trop. Med. Hyg. 2013 Feb;88(2):289-91

 

Dissertations

Completed Dissertations

Below is a list of completed dissertations

2013

Maja Malmberg

The role of molecular markers in emerging artemether-lumefantrine resistant Plasmodium falciparum

2011

Maria Isabel Mendes Veiga

Plasmodium falciparum drug transporter genes in emerging malaria multidrug resistance

2010

Pedro Ferreira

Molecular basis for the mechanism of action and resistance to artemisinin combination therapy in Plasmodium falciparum

Billy Ephraim Ngasala

Improved malaria case management in under-fives in the era of Artemisinin-based combination therapy in Tanzania

Gabrielle Holmgren

Plasmodium falciparum resistance to amodiaquine in monotherapy and in combination therapy with artesunate

2009

Johan Ursing

Plasmodium falciparum response to chloroquine and artemisinin based combination therapy (ACT) in Guinea-Bissau

Sabina Dahlström

Role of PfATP6 and pfMRP1 in Plasmodium falciparum resistance to antimalarial drugs

Christin Sisowath

The molecular basis of Plasmodium falciparum resistance to the antimalarial lumefantrine

2008

Andreas Mårtensson

PCR adjusted cure rates in clinical trials of antimalarial drugs in Africa : Influence of extended follow-up and consecutive day

2007

Seema Gupta

Experimental Pharmacodynamic and Kinetic Studies Related to New Combination Therapies against Falciparum Malaria

2006

Poul Erik Kofoed

Treatment of uncomplicated malaria in Guinea-Bissau

2005

Sandor Bereczky

Genetic diversity of Plasmodium falciparum infections : Influence on protective malaria immunity

Elsa Tynell

Prevention of transfusion transmitted infections : Donor screening and characteristics of recipient populations

2004

Mita Mainu

Atovaquone/proguanil in malaria

Licentiates

2012

Irina Jovel

Spread and distribution of drug resistance and compensatory mutations in Plasmodium falciparum

2009

Mwinyi I. Msellem

Efficacy of artemisinin based combination therapy and effectiveness of rapid diagnostic test for management of patients with Plasmodium falciparum malaria in Zanzibar

Links

Below are a few malaria related links

Information on

Rapid Diagnostic Tests (RDT)

Postal and visiting adress

Malaria Research
Department of Microbiology, Tumor and Cell Biology
Nobels väg 16
SE-17177 Solna
SWEDEN