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Neither the first nor second dose of the monovalent rotavirus vaccine increased the risk of intussusception in the 3 weeks after immunization, a recent study found.

“This finding contrasts with previous studies in high- and upper-middle-income countries, in which an association with intussusception was found,” Jacqueline E. Tate, PhD, of the Centers for Disease Control and Prevention, and her associates reported in the New England Journal of Medicine.

Esben H/iStock/Getty Images
They noted that in 2016, vaccination has prevented an estimated 135,000 hospitalizations and 21,000 deaths from rotavirus infection in the 29 African countries using the vaccine.

“Given these large health benefits, the absence of increased risk of intussusception after RV1 [monovalent Rotarix vaccine] administration in our study is reassuring,” the authors wrote.

An African Intussusception Surveillance Network at 29 hospitals in Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia and Zimbabwe enrolled 1,060 infants younger than age 12 months who experienced intussusception during Feb. 2012-Dec. 2016.

The researchers excluded infants without confirmed record of rotavirus vaccination status or who developed intussusception symptoms when younger than 28 days or older than 245 days. A little more than a third of the remaining 717 infants (36%) were from Ghana, more than half (61%) were male, and their median age was 25 weeks. Only 2% of the children had never received breast milk before developing intussusception symptoms.

The researchers used vaccine cards and clinic records to determine the rotavirus vaccination status for those 717 children with intussusception. The majority of the children (84%) had received both doses of the monovalent rotavirus vaccine. A total of 6% had received only one dose, and 10% received none. Five children received at least one rotavirus vaccine dose after having had intussusception already.

 

 


One intussusception case occurred within the first 7 days after the first vaccine dose, and five cases occurred within a week of the second dose. These incidences were no higher than was the background rate of intussusception, so no increased risk of intussusception in the week after either dose was identified, the researchers said.

The relative incidence of intussusception for dose one during days 1-7 was 0.25 (95% confidence interval, less than .001-1.16), and the relative incidence of intussusception for dose two during days 1-7 was 0.76 (95% CI, 0.16-1.87), Dr. Tate and her associates said.

Incidence of intussusception during the period 8-21 days after vaccination included 6 cases after the first dose and 16 cases after the second dose. Intussusception risk in this extended postvaccination period also was no higher than background risk.

“No clustering of cases occurred in any of the risk windows (1-7 days, 8-21 days, or 1-21 days) after receipt of either dose of RV1,” the authors reported.
 

 

They offered several possible reasons why no increased intussusception risk with rotavirus vaccination occurred in these countries despite studies in middle- and high-income countries showing an increased risk.

“First, although the exact mechanism is not known, intussusception may be related to intestinal replication of the orally administered, live-vaccine rotavirus strain,” Dr. Tate and her colleagues wrote. “Because oral rotavirus vaccines are less efficacious and shedding of vaccine virus – a potential marker of vaccine replication – is less frequently detected in low-income countries than in high- and middle-income countries, rotavirus vaccination might also be associated with a lower intussusception risk in low-income countries.”

Coadministration of rotavirus vaccination with the first dose of oral polio vaccine, which can reduce the rotavirus vaccine’s immunogenicity, also may play a role. Further, the children in this study were vaccinated against rotavirus at age 6- and 10-weeks-old – earlier than the 8 and 16 weeks in middle- and high-income countries – and intussusception is less common under 2 months old, potentially reducing likelihood of an association. Diet, breastfeeding practices, microbiome, maternal antibody levels, or other factors also may be at play.

The research was funded by the Gavi Alliance through the CDC Foundation. Dr. Cunliffe and Dr. Lopman have received personal fees from GlaxoSmithKline and Takeda Pharmaceutical, respectively. The other authors had no disclosures.
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Neither the first nor second dose of the monovalent rotavirus vaccine increased the risk of intussusception in the 3 weeks after immunization, a recent study found.

“This finding contrasts with previous studies in high- and upper-middle-income countries, in which an association with intussusception was found,” Jacqueline E. Tate, PhD, of the Centers for Disease Control and Prevention, and her associates reported in the New England Journal of Medicine.

Esben H/iStock/Getty Images
They noted that in 2016, vaccination has prevented an estimated 135,000 hospitalizations and 21,000 deaths from rotavirus infection in the 29 African countries using the vaccine.

“Given these large health benefits, the absence of increased risk of intussusception after RV1 [monovalent Rotarix vaccine] administration in our study is reassuring,” the authors wrote.

An African Intussusception Surveillance Network at 29 hospitals in Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia and Zimbabwe enrolled 1,060 infants younger than age 12 months who experienced intussusception during Feb. 2012-Dec. 2016.

The researchers excluded infants without confirmed record of rotavirus vaccination status or who developed intussusception symptoms when younger than 28 days or older than 245 days. A little more than a third of the remaining 717 infants (36%) were from Ghana, more than half (61%) were male, and their median age was 25 weeks. Only 2% of the children had never received breast milk before developing intussusception symptoms.

The researchers used vaccine cards and clinic records to determine the rotavirus vaccination status for those 717 children with intussusception. The majority of the children (84%) had received both doses of the monovalent rotavirus vaccine. A total of 6% had received only one dose, and 10% received none. Five children received at least one rotavirus vaccine dose after having had intussusception already.

 

 


One intussusception case occurred within the first 7 days after the first vaccine dose, and five cases occurred within a week of the second dose. These incidences were no higher than was the background rate of intussusception, so no increased risk of intussusception in the week after either dose was identified, the researchers said.

The relative incidence of intussusception for dose one during days 1-7 was 0.25 (95% confidence interval, less than .001-1.16), and the relative incidence of intussusception for dose two during days 1-7 was 0.76 (95% CI, 0.16-1.87), Dr. Tate and her associates said.

Incidence of intussusception during the period 8-21 days after vaccination included 6 cases after the first dose and 16 cases after the second dose. Intussusception risk in this extended postvaccination period also was no higher than background risk.

“No clustering of cases occurred in any of the risk windows (1-7 days, 8-21 days, or 1-21 days) after receipt of either dose of RV1,” the authors reported.
 

 

They offered several possible reasons why no increased intussusception risk with rotavirus vaccination occurred in these countries despite studies in middle- and high-income countries showing an increased risk.

“First, although the exact mechanism is not known, intussusception may be related to intestinal replication of the orally administered, live-vaccine rotavirus strain,” Dr. Tate and her colleagues wrote. “Because oral rotavirus vaccines are less efficacious and shedding of vaccine virus – a potential marker of vaccine replication – is less frequently detected in low-income countries than in high- and middle-income countries, rotavirus vaccination might also be associated with a lower intussusception risk in low-income countries.”

Coadministration of rotavirus vaccination with the first dose of oral polio vaccine, which can reduce the rotavirus vaccine’s immunogenicity, also may play a role. Further, the children in this study were vaccinated against rotavirus at age 6- and 10-weeks-old – earlier than the 8 and 16 weeks in middle- and high-income countries – and intussusception is less common under 2 months old, potentially reducing likelihood of an association. Diet, breastfeeding practices, microbiome, maternal antibody levels, or other factors also may be at play.

The research was funded by the Gavi Alliance through the CDC Foundation. Dr. Cunliffe and Dr. Lopman have received personal fees from GlaxoSmithKline and Takeda Pharmaceutical, respectively. The other authors had no disclosures.

 

Neither the first nor second dose of the monovalent rotavirus vaccine increased the risk of intussusception in the 3 weeks after immunization, a recent study found.

“This finding contrasts with previous studies in high- and upper-middle-income countries, in which an association with intussusception was found,” Jacqueline E. Tate, PhD, of the Centers for Disease Control and Prevention, and her associates reported in the New England Journal of Medicine.

Esben H/iStock/Getty Images
They noted that in 2016, vaccination has prevented an estimated 135,000 hospitalizations and 21,000 deaths from rotavirus infection in the 29 African countries using the vaccine.

“Given these large health benefits, the absence of increased risk of intussusception after RV1 [monovalent Rotarix vaccine] administration in our study is reassuring,” the authors wrote.

An African Intussusception Surveillance Network at 29 hospitals in Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia and Zimbabwe enrolled 1,060 infants younger than age 12 months who experienced intussusception during Feb. 2012-Dec. 2016.

The researchers excluded infants without confirmed record of rotavirus vaccination status or who developed intussusception symptoms when younger than 28 days or older than 245 days. A little more than a third of the remaining 717 infants (36%) were from Ghana, more than half (61%) were male, and their median age was 25 weeks. Only 2% of the children had never received breast milk before developing intussusception symptoms.

The researchers used vaccine cards and clinic records to determine the rotavirus vaccination status for those 717 children with intussusception. The majority of the children (84%) had received both doses of the monovalent rotavirus vaccine. A total of 6% had received only one dose, and 10% received none. Five children received at least one rotavirus vaccine dose after having had intussusception already.

 

 


One intussusception case occurred within the first 7 days after the first vaccine dose, and five cases occurred within a week of the second dose. These incidences were no higher than was the background rate of intussusception, so no increased risk of intussusception in the week after either dose was identified, the researchers said.

The relative incidence of intussusception for dose one during days 1-7 was 0.25 (95% confidence interval, less than .001-1.16), and the relative incidence of intussusception for dose two during days 1-7 was 0.76 (95% CI, 0.16-1.87), Dr. Tate and her associates said.

Incidence of intussusception during the period 8-21 days after vaccination included 6 cases after the first dose and 16 cases after the second dose. Intussusception risk in this extended postvaccination period also was no higher than background risk.

“No clustering of cases occurred in any of the risk windows (1-7 days, 8-21 days, or 1-21 days) after receipt of either dose of RV1,” the authors reported.
 

 

They offered several possible reasons why no increased intussusception risk with rotavirus vaccination occurred in these countries despite studies in middle- and high-income countries showing an increased risk.

“First, although the exact mechanism is not known, intussusception may be related to intestinal replication of the orally administered, live-vaccine rotavirus strain,” Dr. Tate and her colleagues wrote. “Because oral rotavirus vaccines are less efficacious and shedding of vaccine virus – a potential marker of vaccine replication – is less frequently detected in low-income countries than in high- and middle-income countries, rotavirus vaccination might also be associated with a lower intussusception risk in low-income countries.”

Coadministration of rotavirus vaccination with the first dose of oral polio vaccine, which can reduce the rotavirus vaccine’s immunogenicity, also may play a role. Further, the children in this study were vaccinated against rotavirus at age 6- and 10-weeks-old – earlier than the 8 and 16 weeks in middle- and high-income countries – and intussusception is less common under 2 months old, potentially reducing likelihood of an association. Diet, breastfeeding practices, microbiome, maternal antibody levels, or other factors also may be at play.

The research was funded by the Gavi Alliance through the CDC Foundation. Dr. Cunliffe and Dr. Lopman have received personal fees from GlaxoSmithKline and Takeda Pharmaceutical, respectively. The other authors had no disclosures.
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FROM THE NEW ENGLAND JOURNAL OF MEDICINE

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Key clinical point: Intussusception risk was not increased in the 3 weeks after monovalent rotavirus vaccination in seven sub-Saharan countries.

Major finding: The relative incidence of intussusception for dose one during days 1-7 was 0.25 (95% confidence interval, less than .001-1.16), and the relative incidence of intussusception for dose two during days 1-7 was 0.76 (95% CI, 0.16-1.87).

Data source: The findings are based on a self-controlled case-series study involving 717 infants with intussusception and confirmed status of rotavirus vaccination, from Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe.

Disclosures: The research was funded by the Gavi Alliance through the CDC Foundation. Dr. Cunliffe and Dr. Lopman have received personal fees from GlaxoSmithKline and Takeda Pharmaceutical, respectively. The other authors had no disclosures.

Source: Tate JE et al. N Engl J Med. 2018;378:1521-8.
 

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