Research 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.
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.
- George Awungafac, PhD Student
- Alan Dine Courey-Ghaouzi, PhD Student
- Isabelle Eliasson, MD, Affiliated
- Fariba Foroogh, laboratorieansvarig
- Lucille Margerie, Research assistant
- Aurelie Miglar, PhD
- Doreen Mutemi, PhD Student
- David Plaza, Assistant professor
- Ana Requena Mendez, Research Specialist
- Caroline Rönnberg, MD, PhD, Affiliated
- Klara Sondén, MD, PhD, Affiliated
- Christopher Sundling, Principal researcher, Also see: Team Sundling: Inflammation och immunreglering vid infektion
- Rebecca Tafesse Bogale, MD, Affiliated
- Katja Wyss, MD, PhD, Affiliated
- Andreas Wångdahl, MD, PhD Affiliated
- Victor Yman, MD, PhD postdoc
- Pengjun Xi, PhD Student
- Julia Zerebinski, PhD Student
Malaria parasite prevalence in Sub-Saharan African migrants screened in Sweden: a cross-sectional study.
Wångdahl A, Bogale RT, Eliasson I, Broumou I, Faroogh F, Lind F, Vashchuk G, Hildell A, Franson S, Hallberg E, Grip I, Nordling I, Gervin A, Kaitoly S, Tekleab B, Wyss K, Requena-Méndez A, Hertting O, Färnert A
Lancet Reg Health Eur 2023 Apr;27():100581
Systems analysis shows a role of cytophilic antibodies in shaping innate tolerance to malaria.
Lautenbach MJ, Yman V, Silva CS, Kadri N, Broumou I, Chan S, Angenendt S, Sondén K, Plaza DF, Färnert A, Sundling C
Cell Rep 2022 Apr;39(3):110709
Plasmodium falciparum-Specific Memory B-Cell and Antibody Responses Are Associated With Immunity in Children Living in an Endemic Area of Kenya.
Jahnmatz P, Nyabundi D, Sundling C, Widman L, Mwacharo J, Musyoki J, Otieno E, Ahlborg N, Bejon P, Ndungu FM, Färnert A
Front Immunol 2022 ;13():799306
Distinct kinetics of antibodies to 111 Plasmodium falciparum proteins identifies markers of recent malaria exposure.
Yman V, Tuju J, White MT, Kamuyu G, Mwai K, Kibinge N, Asghar M, Sundling C, Sondén K, Murungi L, Kiboi D, Kimathi R, Chege T, Chepsat E, Kiyuka P, Nyamako L, Osier FHA, Färnert A
Nat Commun 2022 Jan;13(1):331
Relapse of Plasmodium vivax and Plasmodium ovale Malaria With and Without Primaquine Treatment in a Nonendemic Area.
Wångdahl A, Sondén K, Wyss K, Stenström C, Björklund D, Zhang J, Hervius Askling H, Carlander C, Hellgren U, Färnert A
Clin Infect Dis 2022 Apr;74(7):1199-1207
Malaria and risk of lymphoid neoplasms and other cancer: a nationwide population-based cohort study.
Wyss K, Granath F, Wångdahl A, Djärv T, Fored M, Naucler P, Färnert A
BMC Med 2020 Oct;18(1):296
Severity of Plasmodium falciparum and Non-falciparum Malaria in Travelers and Migrants: A Nationwide Observational Study Over 2 Decades in Sweden.
Wångdahl A, Wyss K, Saduddin D, Bottai M, Ydring E, Vikerfors T, Färnert A
J Infect Dis 2019 Sep;220(8):1335-1345
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, Karlsson M, Lind I, Nordfjell C, Rooth I, Ngasala B, Homann MV, Färnert A
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, Chen Y, Mikes J, Forsell MN, Sondén K, Achour A, Brodin P, Persson KE, Färnert A
JCI Insight 2019 Apr;5(9):
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, Douhan J, Hammar U, Duijster J, de Gier B, Freedman J, Gysin N, Stark K, Stevens F, Vestergaard LS, Tegnell A, Färnert A
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, Osier FHA, Färnert A
BMC Med 2019 Jan;17(1):22
Obesity and Diabetes as Risk Factors for Severe Plasmodium falciparum Malaria: Results From a Swedish Nationwide Study.
Wyss K, Wångdahl A, Vesterlund M, Hammar U, Dashti S, Naucler P, Färnert A
Clin Infect Dis 2017 Sep;65(6):949-958
High Rate of Treatment Failures in Nonimmune Travelers Treated With Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum Malaria in Sweden: Retrospective Comparative Analysis of Effectiveness and Case Series.
Sondén K, Wyss K, Jovel I, Vieira da Silva A, Pohanka A, Asghar M, Homann MV, Gustafsson LL, Hellgren U, Färnert A
Clin Infect Dis 2017 Jan;64(2):199-206
Antibody acquisition models: A new tool for serological surveillance of malaria transmission intensity.
Yman V, White MT, Rono J, Arcà B, Osier FH, Troye-Blomberg M, Boström S, Ronca R, Rooth I, Färnert A
Sci Rep 2016 Feb;6():19472
Asymptomatic Multiclonal Plasmodium falciparum Infections Carried Through the Dry Season Predict Protection Against Subsequent Clinical Malaria.
Sondén K, Doumbo S, Hammar U, Vafa Homann M, Ongoiba A, Traoré B, Bottai M, Crompton PD, Färnert A
J Infect Dis 2015 Aug;212(4):608-16
Duration of residency in a non-endemic area and risk of severe malaria in African immigrants.
Färnert A, Wyss K, Dashti S, Naucler P
Clin Microbiol Infect 2015 May;21(5):494-501
Breadth of anti-merozoite antibody responses is associated with the genetic diversity of asymptomatic Plasmodium falciparum infections and protection against clinical malaria.
Rono J, Osier FH, Olsson D, Montgomery S, Mhoja L, Rooth I, Marsh K, Färnert A
Clin Infect Dis 2013 Nov;57(10):1409-16
Long-lived Plasmodium falciparum specific memory B cells in naturally exposed Swedish travelers.
Ndungu FM, Lundblom K, Rono J, Illingworth J, Eriksson S, Färnert A
Eur J Immunol 2013 Nov;43(11):2919-29