Professor Emeritus Anders Björkman

My research has historically addressed chal­lenges of improving diagnosis, treatment and control 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.

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.

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.

Malaria facts

  • 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

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 and their fetuses are also more susceptible due to parasite invasion of the placenta.

Symptoms

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.

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

Selected Publications

Influence of cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar.
Pernaute-Lau L, Morris U, Msellem M, Mårtensson A, Björkman A, Gil JP
Malar J 2021 Feb;20(1):90

Safety and efficacy of the Russian COVID-19 vaccine: more information needed.
Bucci E, Andreev K, Björkman A, Calogero RA, Carafoli E, Carninci P, Castagnoli P, Cossarizza A, Mussini C, Guerin P, Lipworth B, Sbardella G, Stocki T, Tuosto L, van Tulleken C, Viola A
Lancet 2020 10;396(10256):e53

Why Asymptomatic Plasmodium falciparum Infections Are Common in Low-Transmission Settings.
Björkman A, Morris U
Trends Parasitol 2020 11;36(11):898-905

Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar.
Msellem M, Morris U, Soe A, Abbas FB, Ali AW, Barnes R, Frumento P, Ali AS, Mårtensson A, Björkman A
Emerg Infect Dis 2020 08;26(8):1767-1777

Parasite clearance, cure rate, post-treatment prophylaxis and safety of standard 3-day versus an extended 6-day treatment of artemether-lumefantrine and a single low-dose primaquine for uncomplicated Plasmodium falciparum malaria in Bagamoyo district, Tanzania: a randomized controlled trial.
Mhamilawa LE, Ngasala B, Morris U, Kitabi EN, Barnes R, Soe AP, Mmbando BP, Björkman A, Mårtensson A
Malar J 2020 Jun;19(1):216

Global coalition to accelerate COVID-19 clinical research in resource-limited settings.
COVID-19 Clinical Research Coalition
Lancet 2020 04;395(10233):1322-1325

WHO's rollout of malaria vaccine in Africa: can safety questions be answered after only 24 months?
Aaby P, Fisker AB, Björkman A, Benn CS
BMJ 2020 01;368():l6920

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

An online mapping database of molecular markers of drug resistance in Plasmodium falciparum: the ACT Partner Drug Molecular Surveyor.
Otienoburu SD, Suay I, Garcia S, Thomas NV, Srisutham S, Björkman A, Humphreys GS
Malar J 2019 Jan;18(1):12

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.
West African Network for Clinical Trials of Antimalarial Drugs (WANECAM)
Lancet 2018 04;391(10128):1378-1390

Asymptomatic low-density malaria infections: a parasite survival strategy?
Björkman AB
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

Publication in Trends in Parasitology

Why Asymptomatic Plasmodium falciparum Infections Are Common in Low-Transmission Settings.
Björkman A, Morris U
Trends Parasitol 2020 11;36(11):898-905

Contact

Anders Björkman

Professor Emeritus/Emerita
C1 Department of Microbiology, Tumor and Cell Biology