The Anders Björkman Malaria Project - Malaria treatment and control
Our research has historically addressed challenges of improving diagnosis, treatment and control of Plasmodium falciparum malaria.
Improving Diagnosis, Treatment and Control/Elimination of Plasmodium falciparum Malaria
A major aim has continuously been to apply new biomedical technologies to respond to parasitological, clinical and epidemiological research questions. That implies studies on diagnostic technologies and malaria therapies and studies on the possible evolution and selection of different genetic parasite alterations potentially associated to resistance to detection, diagnosis and/or treatment of P. falciparum. A main overall aim is to address the research question “is it possible to eliminate malaria from a high endemic region, typical of sub Saharan Africa?” Our main research site is Zanzibar where our project has been uniquely successful reaching “pre-elimination”. We are now exploring new interventions to possibly and further uniquely reach elimination of the locally residual transmission.
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.
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
Malaria is curable
There are approx 250 million cases of malaria each year
Malaria causes approx half a million deaths each year
3,3 billion people live in areas of malaria transmission
Malaria societal costs are estimated to be 12 billion USD per year in Africa alone
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 and their fetuses are also more susceptible due to parasite invasion of the placenta.
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.
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.
For more information about malaria, please visit the WHO malaria website.
Our publication in the journal "Trends in Parasitology". If a Plasmodium falciparum malaria infection has no clinical symptoms is believed to be a result of protective immunity which only develops after years of many repetitive clinical episodes. We show that asymptomatic infections can occur also in previously unexposed individuals in Zanzibar, Tanzania, where transmission has reached a very low level in the last ten years. Relating our 17 year epidemiological data to a a number of published laboratory based experimental data, we conclude that asymptomatic and low-density parasitemias may actually be selected for in low-transmission settings because parasites with low virulence and fitness will have a selective advantage over highly virulent parasites, whereas the opposite would be true in high-transmission areas. This new explanation has major implications for our understanding of the epidemiology of malaria and above all for its optimal control and elimination strategies.
Read the publication in the journal "Trends in Parasitology".
From high to low malaria transmission in Zanzibar-challenges and opportunities to achieve elimination.
Björkman A, Shakely D, Ali AS, Morris U, Mkali H, Abbas AK, et al
BMC Med 2019 01;17(1):14
Pyronaridine-artesunate or dihydroartemisinin-piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b/4 trial.
Lancet 2018 04;391(10128):1378-1390
Asymptomatic low-density malaria infections: a parasite survival strategy?
Lancet Infect Dis 2018 05;18(5):485-486
Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis.
Kloprogge F, Workman L, Borrmann S, Tékété M, Lefèvre G, Hamed K, et al
PLoS Med. 2018 06;15(6):e1002579
Plasmodium falciparum Plasmepsin 2 Duplications, West Africa.
Inoue J, Silva M, Fofana B, Sanogo K, Mårtensson A, Sagara I, et al
Emerging Infect. Dis. 2018 08;24(8):
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 KJ, Cairns ME, Chandler CI, Leurent B, Ansah EK, et al
BMJ 2017 Mar;356():j1054
Spatial Distribution of Falciparum Malaria Infections in Zanzibar: Implications for Focal Drug Administration Strategies Targeting Asymptomatic Parasite Carriers.
Björkman A, Cook J, Sturrock H, Msellem M, Ali A, Xu W, et al
Clin. Infect. Dis. 2017 05;64(9):1236-1243
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 IT, Björkman A, Roper C, Mårtensson A, Ursing J
Malar. J. 2017 03;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 XC, Jovel I, Msellem MI, Bergman D, et al
PLoS ONE 2017 ;12(1):e0169037
Sustained High Cure Rate of Artemether-Lumefantrine against Uncomplicated Plasmodium falciparum Malaria after 8 Years of Its Wide-Scale Use in Bagamoyo District, Tanzania.
Mwaiswelo R, Ngasala B, Gil JP, Malmberg M, Jovel I, Xu W, et al
Am. J. Trop. Med. Hyg. 2017 Aug;97(2):526-532
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 AS, Bachelard M, et al
PLoS ONE 2016 ;11(1):e0146054
Safety and efficacy of re-treatments with pyronaridine-artesunate in African patients with malaria: a substudy of the WANECAM randomised trial.
Sagara I, Beavogui AH, 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 AK, Msellem MI, Nassor MH, et al
Malar. J. 2015 May;14():205
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 MI, 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 MI, 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 IJ, Bell D, Edlund E, Nassor MH, et al
Malar. J. 2015 Jan;14():43
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
Loop mediated isothermal amplification (LAMP) accurately detects malaria DNA from filter paper blood samples of low density parasitaemias.
Aydin-Schmidt B, Xu W, González IJ, Polley SD, Bell D, Shakely D, et al
PLoS ONE 2014 ;9(8):e103905
Below is a list of completed dissertations from the last 10 years
The role of molecular markers in emerging artemether-lumefantrine resistant Plasmodium falciparum
Maria Isabel Mendes Veiga
Plasmodium falciparum drug transporter genes in emerging malaria multidrug resistance
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
Plasmodium falciparum resistance to amodiaquine in monotherapy and in combination therapy with artesunate
Plasmodium falciparum response to chloroquine and artemisinin based combination therapy (ACT) in Guinea-Bissau
Role of PfATP6 and pfMRP1 in Plasmodium falciparum resistance to antimalarial drugs
The molecular basis of Plasmodium falciparum resistance to the antimalarial lumefantrine
PCR adjusted cure rates in clinical trials of antimalarial drugs in Africa : Influence of extended follow-up and consecutive day
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
Postal and visiting adress
Department of Microbiology, Tumor and Cell Biology
Solna vägen 9
171 65 Solna