Investigating the incidences and risks of rotavirus-associated extraintestinal complications in hospitalized children under 5

Rotavirus infections among young children are extremely common, but their long-term complications have been less explored.

In a recent study published in The Journal of Infectious Diseases, researchers focused on extraintestinal complications of rotavirus infections in children below the age of five years.

Study: Increased Risk of Neurological Disease Following Pediatric Rotavirus Infection: A Two-Center Case-Control Study. Image Credit: chairoij/Shutterstock.com

Introduction

Rotavirus infections, mostly caused by rotavirus A, cause watery secretory diarrhea leading to dehydration and electrolyte imbalances, especially among young children. It endangers more children in this age group than any other cause of acute gastroenteritis.

Of the ~130,000-200,000 children who die of rotavirus infections every year, from among the approximately 260 million pediatric cases worldwide, most are in low-resource countries. This has spurred the rollout of universal rotavirus vaccination. However, no specific treatment is yet available.

Some studies indicate that apart from acute gastroenteritis, a systemic infection may lead to multiple other complications. These may include acute neurological disease (ND), type 1 diabetes, hepatobiliary disease, respiratory disease, heart disease, and kidney failure.

However, little is known about these sequelae. This prompted the current study to investigate the incidence and risk of extraintestinal complications of rotavirus infection in young children.

What did the study show?

The study included ~1,300 inpatients with rotavirus infection and ~1,800 controls. The neurological disease was more frequent among the former group.

About seven percent of rotavirus patients in newborns developed ND vs. <3% of controls. The corresponding figures for infants and young children with mild gastroenteritis were ~18% vs 12%, respectively. Where severe gastroenteritis occurred, the incidence was 21% vs. 11% in cases and controls, respectively.

In the whole cohort, there was an increase in heart disease incidence post-rotavirus, at 10%, vs. 6% in controls. In infants and young children with mild gastroenteritis, the incidence of ND was 9% vs. 5% in controls. The hepatobiliary disease occurred in 13% of mild rotavirus gastroenteritis cases vs. 8% of controls.

With properly matched cases and controls, ND occurred in ~22% of cases vs. ~10% of controls. In this set, no other complications were significantly higher after rotavirus infection.

The odds of ND thus increased significantly post-rotavirus. Following mild and severe gastroenteritis, the odds of ND were increased by 50% and 120%, respectively, in infants and young children.

This puts newborns at two-and-a-half times higher odds for ND following rotavirus infection than controls and infants/young children at twice the risk. After adjusting for confounding factors, the odds remained almost twice as high in a group of cases with well-matched controls.

The odds of developing heart disease were 50% higher in newborns, infants, and young children with mild rotavirus gastroenteritis. Other illnesses failed to show significant correlation once confounding factors were accounted for.

The development of extraintestinal complications impacts the clinical outcomes of gastroenteritis as well, with differences in the mean period of hospitalization between cases and controls.

When rotavirus infection was associated with hepatobiliary or respiratory disease, the mean duration of hospitalization went up, while the cumulative discharge rate decreased by ~25% and 10%, respectively.

What are the implications?

Neurological disease is confirmed in this study as the second leading extraintestinal complication of rotavirus infection in young children, with the respiratory illness being the first. A third to two-thirds of children with rotavirus infection develop respiratory problems.

Rotavirus infection is a risk factor for seizures, which complicate 2-8% of such infections in children, and push up the risk four-fold.

Rotavirus vaccination in the USA has reduced the prevalence of seizures among children, supporting this hypothesis.

Interestingly, newborns with rotavirus, and severe infection, were risk factors for ND at a higher incidence compared to infants and young children or mild gastroenteritis.

This may be traceable because rotavirus-induced gut symptoms are more likely to be severe when the child has an immature immune response.

At the same time, the enteric and central nervous systems are activated by the vomiting and diarrhea induced by rotavirus infection, again pointing to the possibility of increased neurological risk following severe gastroenteritis caused by rotavirus. Cerebrospinal fluid has been found to be positive for rotavirus, viral antigens, antirotavirus antibodies, and genomic RNA.

During replication, rotavirus yields the protein NSP4, a viral enterotoxin that may also be associated with neurological injury. However, the virus has not yet been demonstrated to be directly toxic to the neurons.

Heat disease is also more likely following rotavirus infection in young children, but hepatobiliary disease is only more common in cases with mild gastroenteritis.

Rotavirus vaccination has reduced rotavirus-associated hospitalizations and deaths by 25% to 55%, but up to a tenth of children with gastroenteritis still test positive for the virus.

This percentage rises to 35-40% in hospitalized children. Areas with low vaccine coverage should adopt this measure to prevent prolonged hospitalization and extraintestinal complications.

Conclusion

The study findings should help to raise clinical awareness of the potential for serious extraintestinal complications of rotavirus gastroenteritis and adverse outcomes, including duration of hospitalization and discharge rates.