Human enteroviruses and parechoviruses: disease spectrum and need for treatment in young children

Human parechoviruses (HPeVs) and enteroviruses (EVs) are amongst the most prevalent viruses in children and elicit a wide range of disease from mild illness to life-threatening infections. With the introduction of novel molecular diagnostic methods (like PCR), the detection rate of these viruses has been increased substantially, which has led to questions about the clinical relevance of a positive PCR. In the first part of this thesis is described that these viruses are very prevalent in symptomatic as well as asymptomatic young children and that these viruses are able to cause severe disease. Viral load in stool and respiratory samples cannot distinguish between symptomatic and asymptomatic infection.
The second part of this thesis focused on treatment against EVs and HPeVs. Treatment is necessary and urgently needed in severe HPeV and EV infections. Until now there is no effective antiviral drug available for severe infections. The only drug that has been tested in phase III trials is pleconaril, which has broad-spectrum activity against most EVs (including rhinoviruses), but was never approved by the FDA. In this thesis is shown that treatment with pleconaril can be effective in severe EV infections, but that resistance can occur. In this thesis is also shown that neutralizing antibodies play an important role in the host defense against most EVs and HPeVs, giving a rationale for treatment with intravenous immunoglobulins or monoclonal antibodies. More knowledge of the pathogenesis and host response against EVs and HPeVs is essential to develop effective treatment strategies in the future.