Role of neutralizing (maternal) antibodies in protection against human parechovirus infection and other risk factors for picornavirus infection in young children.

EV infections are generally recognized as among the most common causes of
sepsis or meningitis in young children. The clinical importance of HPeV
infection in young children and especially neonates is increasingly recognized.
In some children the morbidity is considerable with sepsis-like illness or/and
meningitis and possible long term sequelae. However, no effective treatment is
known. Since lack of type-specific antibodies in neonates is a risk factor for
symptomatic neonatal EV infection, Intravenous immunglobuline (IVIg) is
sometimes given in severe neonatal sepsis, but results are inconclusive. This
could be due to differences in the circulating strains causing (severe)
morbidity, and the antibodies present in IVIg against EV strains that have been
circulating in the past. However, the protective role of antibodies against
EV/HPeV infections has never been proven. The occurrence of over 100 EV
serotypes with a large diversity of clinical syndromes makes it difficult to
study this group of viruses. The new group of HPeVs only contains six
genotypes, with a distinct difference in severity of disease between HPeV1 and
HPeV3, the most prevalent genotypes. Furthermore, the seroprevalence in adults
of HPeV1 and 3 antibodies is much higher than for the EV serotypes. This
differences, combined with their clinical and biological resemblance to the
EVs, makes HPeV infection a suitable model for studying picornavirus
pathogenesis.

The aim of this study is to determine the risk factors in infants for obtaining
a severe HPeV infection. For this purpose, we will test the hypothesis that
(maternal) HPeV specific antibodies are protective against (severe) HPeV
infections in young children. This will support, or reject, the rationale for
antibody therapy in HPeV infection.
Furthermore, we will study the importance of viral and host factors in
pathogenesis of picornavirus infections. Next to the presence or absence of
maternal antibodies, viral load, virus tropism, or genetic host factors like
polymorphisms or production of cytokines could influence severity of disease.

A case-control study of mother and child pairs to evaluate the role of maternal
antibodies against HPeV-infection in young children and to determine other risk
factors.
The cases are defined as HPeV positive and the controls are defined as HPeV
negative and either EV positive or also EV negative.

For this study a single blood sample will be obtained from the infants and
their mothers. If possible, this sample will be obtained together with
necessary blood samples for treatment. Untill now, no serious adverse reactions
are known from a single venous punction.
A stool sample is also obtained for diagnostics of HPeV ad EV infection.
Additional stool samples of HPeV positive infants will be obtained every two
weeks, until HPeV is negative.
The aim of this study is to determine the role of (maternal) antibodies. If
these antibodies are protective, they possibly can be used as medicine for this
serious infection in the future .
We think this possible benefit for the future outweight the risks for
participating in this study.