A study of the WHO VigiBase database was conducted after reports of recurrent cases of hematemesis (vomiting of blood) on the same day after two doses of a vaccine for the prevention of rotavirus infection in a healthy child.
As of March 2020, 129 reports of reactions associated with this medicinal product had been registered in VigiBase. This is more than expected compared with the background rate of the database. In 52 cases the rotavirus vaccine was the only suspected drug, and in 42 cases it was the only reported drug (no concomitant therapy). In 33 reports intussusception was additionally described; four of them concerned the Rotashield vaccine, which has been withdrawn from circulation. For reports describing intussusception as a concomitant condition, the time to onset of the reaction was generally longer (a median of slightly more than two weeks) compared with a median of 3 days for all reports, which indicated two different mechanisms of bloody vomiting. In 2 reports the administration of a second dose of the rotavirus vaccine was described, after which the children again developed hematemesis. Based on the reports received by VigiBase, there is a risk that the vaccine may cause gastroenteritis-induced bloody vomiting in some individuals, with or without intussusception. Further studies are needed to establish this potential. In the meantime, if bloody vomiting is observed after rotavirus vaccination, it is recommended to carefully assess the situation before re-administering the vaccine.
Rotavirus vaccine is a live attenuated vaccine for the prevention of rotavirus, indicated for active immunization against gastroenteritis caused by rotavirus infection. It is used from the age of 6 weeks, preferably before 16 weeks, and vaccination must be completed by week 24. The vaccination course consists of two doses, with an interval of at least four weeks between them.
Rotavirus infection is the most common cause of severe diarrhea in infants and young children and is transmitted by the fecal-oral route through contact with the feces of an infected person. Most children with rotavirus diarrhea recover on their own. However, some children become ill with severe vomiting, diarrhea, and life-threatening dehydration that requires hospitalization.
Hematemesis is vomiting of blood caused by bleeding in the esophagus, stomach, or duodenum. The color and volume of the vomit indicate how long the blood has been in the stomach. Dark blood or "coffee grounds" indicates minor bleeding; the color changed on contact with stomach acid. A large volume of bright red blood indicates rapid, larger-volume hemorrhage. In a child with hematemesis, the source of bleeding is the upper gastrointestinal tract. Children who have bright red blood in the stool or bloody diarrhea usually have bleeding in the lower gastrointestinal tract, most likely in the colon.
The differential diagnosis of hematemesis in infants includes bleeding from the upper gastrointestinal tract (most often from esophagitis or gastritis); coagulopathies, including those caused by vitamin K deficiency; platelet dysfunction or clotting factor deficiency; swallowed blood from the nasopharynx or airways, or swallowed maternal blood, which is the most common etiology in newborns. Ingestion of substances such as food dyes and red dyes has also been described as being mistaken for blood. Less often, the causes of pediatric hematemesis are a gastric ulcerated tumor, Dieulafoy lesion (arterial malformation) and hereditary hemorrhagic telangiectasia.
Discussion and conclusions
It is known that hematemesis can occur with a duodenal ulcer, which is sometimes caused by rotavirus gastroenteritis. This information is stated in the package leaflet with a frequency of "not known," in infants with severe combined immunodeficiency. In VigiBase there are 981 reports of gastroenteritis after vaccination against rotavirus infection compared with 34 expected cases. Only in 2 reports is information on the presence of severe combined immunodeficiency provided, which indicates that gastroenteritis caused by the rotavirus vaccine, which may result in hematemesis, can also occur in children without this deficiency.
Among 129 reports of hematemesis in VigiBase, the time to onset of the reaction is short and fairly consistent. Most cases were serious, and five were fatal. In 52 reports, the rotavirus infection prophylaxis vaccine was the only suspected drug, and in 42 reports no other medicinal products were used. In 3 reports, concomitant use of medicinal products other than vaccines was noted. In all other reports where concomitant administration of other vaccines was noted, the rotavirus vaccine was the only one administered orally. In 2 cases, recurrence of the adverse reaction after re-administration (positive rechallenge) was noted, and the causal relationship was stated as certain in one of these reports. In cases where intussusception was also reported, hematemesis could potentially be explained by gastric perforation, which sometimes occurs as a complication of intussusception. However, for most reports there is no other obvious alternative cause. Vitamin K deficiency can lead to bleeding in infants, but vitamin K administration to newborns is recommended worldwide.
The fact that healthcare professionals assess bloody vomiting as unrelated to the vaccine because this information is not stated in the instructions for medical use (as indicated in one report) is a problem. Failing to see a potential link with the use of the vaccine is likely to lead to administration of a second dose and an additional risk of potentially developing hematemesis, as observed in reports received by VigiBase.
Although vaccination against rotavirus infection remains important for children's health, preventing serious illness or death of many children worldwide, there is a risk that the vaccine may cause gastroenteritis and hematemesis in certain individuals. Further studies establishing this possibility are needed, and in the meantime it may be advisable to remain vigilant for symptoms. If such symptoms occurred after the first vaccination, caution should be exercised before re-administering the vaccine.
More information on vaccines for the prevention of rotavirus infection and cases of hematemesis is described in the original document Uppsala Monitoring Centre “Rotavirus vaccine – haematemesis”.
List of vaccines for the prevention of rotavirus infection authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 28.04.2020).
