Group Anna Färnert
Malaria remains a major global health problem and new tools are needed to reduce malaria morbidity and mortality and eventually reach the goals of elimination. Development of an efficacious vaccine will require further understanding of how natural immunity to malaria is acquired and maintained. Our group is particularly interested in the importance of the extensive diversity of parasite antigens and mechanisms involved in the maintenance of protection. The molecular and sero-epidemiology of malaria is studied in a longitudinal population cohort in areas of varying transmission in Sub-Saharan Africa. Moreover, immune responses are studied in depth in a cohort of patients successfully treated for malaria and prospectively followed in Sweden, thus without risk of reinfection. Immunological memory is studied in the context of different infections and vaccines. In addition, we assess long term effects of malaria and other infections on the host including ageing biology. In a nation wide study of malaria in Sweden we investigate host factors, such as comorbidities, in relation to the risk of severe malaria, with aim to improve the clinical management and prevention of malaria.
ACQUISITION AND MAINTENANCE OF IMMUNITY TO MALARIA
Molecular epidemiology of malaria
Understanding how natural immunity to malaria develops in populations living in endemic areas can guide the development of vaccines and other malaria interventions. Molecular and immunological tools are used to investigate the epidemiology of malaria in populations with different degrees of exposure. The genetic diversity of parasite antigens is studied in relation to disease and immune responses, in closely followed population cohorts in areas of different transmission. We have previously shown that individuals in endemic areas that are persistently infected with multiple parasite clones are at reduced risk of clinical malaria and also have broader antibody responses. Current projects investigate the importance of repeated and chronic infections to the maintenance of otherwise short lived antibody responses, as well as the importance of the extensive genetic diversity of parasite antigens for the acquisition clinical protection against malaria.
CLINICAL EPIDEMIOLOGY AND MANAGEMENT OF MALARIA
The outcome of a malaria infection is largely affected by the acute clinical management. In addition to the morbidity and mortality due to acute disease, malaria might also have longterm consequences on health. As part of a nationwide study in Sweden, we assess factors affecting severe malaria including maintenance of immunity and comorbidities such as diabetes and obesity. By using national health registers and individual medical record data we study acute and longterm effect of malaria in relation to host factors. In addition, we study the epidemiology of malaria in in a longitudinally followed population in Tanzania. These projects focus on clinical aspects of malaria, including prognostic factors, diagnostics and therapy, with the overall aim to improve the management and prevention of malaria.
MALARIA AND VACCINE IMMUNOLOGY
Mechanistic insights into the control of long-lived humoral immunity
Vaccines work by stimulating the immune system with components of pathogens without experiencing a fullblown infection. However, although the protective effect of most licensensed vaccines is very high, the durability of the protection varies widely between vaccines. The tick-borne encephalitis virus (TBEV) vaccine, e.g. needs to be boosted every three to five years while the measles vaccine generally generates protective immunity for the life-time of the individual. Live vaccines, such as the measles vaccine, generally induce immunity that lasts longer compared to inactivated- or subunit vaccines, such as the TBEV or tetanus vaccines, as they more closely mimick the natural infection. However, not all natural infections lead to long-lasting immunity. Individuals that were previously immune to malaria disease can become susceptible again after staying in non-endemic regions for a few years, indicating that malaria-specific immunity is very short-lived.
It is currently unclear why there is such a difference in the longevity of immunity and this is an important problem to solve, so that current and future vaccines can be improved and generate longer lasting immunity. To increase our understanding of the mechanisms that govern longevity of an immune response we use molecular approaches to investigate antigen-specific immune cells at different time-points after vaccination or infection that induce long- or short-lived immunity. This approach enable us to better understand how the immune cells are programmed in the context of long- vs short-lived immunity, and thereby help guide future vaccine efforts.
Changes to the immune landscape after malaria infection
Malaria infection is associated with a strong activation of the innate immune response. This activation is characterized by high levels of interferon gamma, which is characteristic of a Th1 immune response. The innate signal type and strength is important inshaping the size and direction of the adaptive immune response. In recent years, it has become clear that the strong Th1 signal observed during malaria infection may have implications for the longevity and reactivation of the adaptive immune response. Current projects investigate the immune landscape in individuals that experience malaria for the first time, or that have experienced malaria previously. Using mass cytometry, we have found that the innate and adaptive immune profiles differ in the monocyte, T cell, NK cell, and B cell compartments between the groups, findings that are currently being investigated further.
Anna Färnert, Professor Senior Consultant, Head of Division
Akua Botwe, PhD student
Peter Jahnmatz, PhD student
Klara Sondén, MD, PhD
Christopher Sundling, PhD, Research Assistent Professor
Andreas Wångdahl, MD, PhD student
Katja Wyss, MD, PhD student
Victor Yman, MD, PhD
Franics Ndungu, Senior researcher
Doreen Mutemi, PhD student
Fariba Foroogh, Labaratory Manager
Maximillian Julius Lautenbch, Research Assistent
MD, PhD, Principal Investigator
Work:+46 (0)8-517 752 85
Persistent transmission of Plasmodium malariae and Plasmodium ovale species in an area of declining Plasmodium falciparum transmission in eastern Tanzania.
Yman V, Wandell G, Mutemi DD, Miglar A, Asghar M, Hammar U, et al
PLoS Negl Trop Dis 2019 May;13(5):e0007414
B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets.
Sundling C, Rönnberg C, Yman V, Asghar M, Jahnmatz P, Lakshmikanth T, et al
JCI Insight 2019 Apr;5():
Malaria in Eritrean migrants newly arrived in seven European countries, 2011 to 2016.
Sondén K, Rolling T, Wångdahl A, Ydring E, Vygen-Bonnet S, Kobbe R, et al
Euro Surveill. 2019 Jan;24(5):
Antibody responses to merozoite antigens after natural Plasmodium falciparum infection: kinetics and longevity in absence of re-exposure.
Yman V, White MT, Asghar M, Sundling C, Sondén K, Draper SJ, et al
BMC Med 2019 01;17(1):22
KILchip v1.0: A Novel Plasmodium falciparum Merozoite Protein Microarray to Facilitate Malaria Vaccine Candidate Prioritization.
Kamuyu G, Tuju J, Kimathi R, Mwai K, Mburu J, Kibinge N, et al
Front Immunol 2018 ;9():2866
Cutaneous, mucocutaneous and visceral leishmaniasis in Sweden from 1996-2016: a retrospective study of clinical characteristics, treatments and outcomes.
Glans H, Dotevall L, Söbirk SK, Färnert A, Bradley M
BMC Infect. Dis. 2018 Dec;18(1):632
The Malaria-Protective Human Glycophorin Structural Variant DUP4 Shows Somatic Mosaicism and Association with Hemoglobin Levels.
Algady W, Louzada S, Carpenter D, Brajer P, Färnert A, Rooth I, et al
Am. J. Hum. Genet. 2018 11;103(5):769-776
Liver Injury in Uncomplicated Malaria is an Overlooked Phenomenon: An Observational Study.
Reuling IJ, de Jong GM, Yap XZ, Asghar M, Walk J, van de Schans LA, et al
EBioMedicine 2018 Oct;36():131-139
Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo.
Parigi SM, Czarnewski P, Das S, Steeg C, Brockmann L, Fernandez-Gaitero S, et al
Sci Rep 2018 01;8(1):154
Cellular aging dynamics after acute malaria infection: A 12-month longitudinal study.
Asghar M, Yman V, Homann MV, Sondén K, Hammar U, Hasselquist D, et al
Aging Cell 2018 02;17(1):
Detection of Malaria Parasites After Treatment in Travelers: A 12-months Longitudinal Study and Statistical Modelling Analysis.
Vafa Homann M, Emami SN, Yman V, Stenström C, Sondén K, Ramström H, et al
EBioMedicine 2017 Nov;25():66-72