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Serious complications following infectious diseases in healthy children and paediatric patients with underlying comorbidities

Infections are still one of the leading worldwide cause of death among children under 5 years. Despite a low mortality rate in Sweden, infectious diseases are among most common reasons behind health care contact, and hospitalization of children with or without underlying comorbidities. The pattern and type of childhood infections have changed along with changes in the national childhood vaccination programs. For instance, a marked reduction of children with pneumococcal meningitis was noted following introduction of the pneumococcal immunization in to the Swedish national vaccination program. Likewise, reported cases of measles infections from Swedish hospitals are very rare due to our high national measles vaccine coverage.

The clinical and epidemiological studies conducted here are together with paediatric infectious disease specialists, who assess the changes in infection type and patterns over time, during childhood. For instance, we monitor the coverage of the national childhood vaccination program in term and pre-term children. Our other study cohorts consist of both healthy children and those needing extra health care due to their underlying comorbidities, such as cancer and autoimmunity. Indeed, there are individual variations among paediatric cancer patients concerning episodes and severity of infections during and after chemotherapy treatment. We aim to understand the reason behind this observation by examining the connection between genetic polymorphisms in the innate immune system and infection type and frequency.

Principal investigator:
, MD, PhD, Chief physician, Associate Professor

Students and collaborators:
, MD, PhD Student
, MD, PhD Student
, MD, PhD student
Martina Söderman, MD, PhD Student
Joseph Mathew, MD, PhD
Anna Berggren, MD, PhD
, PhD, Assistant Professor
, MD, Associate Professor
Eva Sverremark-Ekström, PhD, Professor

The short and long-term effects of conventional and metronomic chemotherapy regimens on the cell-mediated immune system of children

Despite the contribution of vaccines to global health, our immune system has the capacity to control the majority of infections by itself. Human herpesviruses belong to the latter category of infections, which are tightly controlled by our immune system after the initial encounter usually occurring in childhood. Through their long co-evolution with humans, following primary infection herpesviruses have managed to find mechanisms to hide from the immune system and persist in a clinically silent state for life. Despite this, some findings suggest that these viruses can influence the antibody-mediated immune response to vaccines and environmental antigens. In the otherwise healthy host, herpesvirus latency is a rule since T- and to some degree NK-cells, which can kill virus-infected cells, keep herpesviruses under control by constantly patrolling the body. In immunocompromised patients on the other hand, herpesviruses can become reactivated and cause serious health complications.

Through this project we want to understand how the capacity of T- and NK-cells to combat infectious agents is affected by current chemotherapy protocols and immunosuppressive drugs. After stimulation with Doxorubicin or Methotrexate, we monitor cell-mediated immune responses against two common herpesviruses, Epstein-Barr virus and cytomegalovirus. Within this context, the association between gut microbiota and priming of antiviral responses is investigated. The ongoing experiments are in vitro, with cells derived from healthy blood donors, paediatric cancer patients or patients with chronic disorders.

Students and collaborators:
Gintare Lasaviciute, PhD Student
Anna Höbinger, PhD Student
Rayan Chikhi, PhD, CNRS Researcher
Mats Bemark, PhD, Scientist
, MD, PhD, Chief physician, Associate Professor
Eva Sverremark-Ekström, PhD, Professor