a-t 2015; 46: 49

... France withdraws recommendation for vaccination

The risk of intussusception, i.e. of a proximal (upper) section of the intestine folding into a distal (lower) section, is higher after a rotavirus vaccination (ROTARIX, ROTATEQ) and apparently highest during the first seven days after oral administration of the first dose of the vaccine (a-t 2010; 41: 129-30). Post-marketing surveillance data for both vaccines indicate an increase of up to six additional intussusceptions for every 100,000 infants/year (a-t 2013; 44: 76, 81) relative to an average incidence rate of around 30-100 intussusceptions for every 100,000 infants (under one year)/year (1,2).

France is currently withdrawing its recommendation to routinely vaccinate infants against rotavirus issued at the end of 2013 (3). This decision has been made in response to pharmacovigilance data collected in France between May 2006 and October 2014 according to which intussusceptions that develop after vaccination have the potential to be more severe than those that form spontaneously (4). During the period of surveillance, the French National Agency for Medicines and Health Products Safety ANSM documented reports on 47 infants that developed intussusceptions within 30 days of the oral vaccination, and which led to the death of 2 children. 14 required surgical interventions, 3 of which comprised partial bowel resections, and 2 required resuscitation (4,5). On average, around 20% of infants under the age of six months require surgical interventions in France. Fatalities are exceptions and generally due to delayed or inadequate treatment (3,5).

The intussusceptions after vaccination were furthermore observed at an earlier age than common for intussusceptions: On average, affected vaccinated infants have a median age of three months, while 80% of spontaneous intussusceptions develop in infants over the age of six months (3,4). The French National Agency for Medicines and Health Products Safety believes that this may have been a contributing factor to the severity of the cases. Furthermore, the symptoms of intussusceptions that appeared after vaccination may have been misinterpreted and medical help may therefore have been sought too late (4). Based on the new data, the French authorities have concluded that risk-benefit balance of rotavirus vaccinations is negative for an industrialized country such as France (3,5).

The German Paul-Ehrlich-Institute (PEI) issued a safety information in response to the proceedings in France (6). However, this information does not contain any details on the decision made by the French authorities or the deaths recorded in France. Notwithstanding, the PEI appeals to pediatricians urgently to inform parents of the threatening adverse effect and its symptoms before the vaccination, which the German Standing Committee on Vaccination (STIKO) has been recommending since 2013, to ensure that medical help is sought without delay if there are signs of intussusceptions such as spasmodic abdominal pain, unusual crying, refusal to eat, vomiting and in particular blood in the stool. According to the authority, intussusceptions can be prevented from turning severe by starting treatment as quickly as possible. The institute has received 82 reports of confirmed intussusceptions after rotavirus vaccinations from within Germany. In 12 of the children, part of the intestine had to be removed. Apparently, there have not been any reports of deaths (6).

 France has withdrawn its recommendation for routinely vaccinating all infants against rotavirus. This decision is based on national pharmacovigilance data according to which intussusceptions that develop after vaccination are potentially more severe than those that develop spontaneously and as a result of which rotavirus vaccinations are not considered to have a positive benefit-risk balance for an industrialized country.

 We already voiced our objections to routinely vaccinating all infants against rotavirus in our initial assessment in 2008 (a-t 2008; 39: 111-4).

 If children are to be vaccinated against rotavirus, it is vital that parents are informed of the signs of intussusceptions and of the importance of seeking medical help without delay if there are any indications of this complication.

1 GSK: Summary of Product Characteristics (SPC) ROTARIX Suspension, as at Apr. 2014
2 Sanofi Pasteur MSD: SPC ROTATEQ Lösung, as at March 2014
3 Haut Conseil de la Santé Publique: Avis relatif a la vaccination des nourissons vis-à-vis des gestroentérites à rotavirus as at 21 Apr. 2015
4 ANSM: Suivi national de pharmacovigilance des vaccins ROTARIX et ROTATEQ; Febr. 2015
5 Haute Autorité de Santé: Avis ROTATEQ/ROTARIX as at 1 Apr. 2015
6 PEI: Information zu Fällen von Darminvagination nach Impfung gegen Rotavirus-Gastroenteritis [information on cases of intussusception following vaccination against rotavirus gastroenteritis] as at 11 May 2015

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