Immune Response of Children Who Develop Persistent Diarrhea following Rotavirus Infection

Abstract

A prospective study was conducted with Bangladeshi children with rotavirus (RV) diarrhea to assess whether nutritional and clinical parameters, RV serotypes, levels of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), and RV-specific antibody titers in plasma and stool were associated with the development of persistent diarrhea. Children with watery diarrhea for 6 to 8 days, selected from the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), were enrolled in the study and monitored until diarrhea improved. Children were classified as having acute diarrhea (AD) if diarrhea resolved within 14 days of onset and as having persistent diarrhea (PD) if diarrhea persisted for more than 14 days after onset. Uninfected, control children (n = 13) from the Nutrition Follow-Up Unit of ICDDR,B were also enrolled. Of the 149 children with diarrhea enrolled, 29 had diarrhea with RV alone, of which 19 had AD and 10 developed PD. Samples of stool and blood were collected from all children on enrollment. Stool samples were collected again from children when they developed PD. Of the 10 children who had an initial RV infection and then developed PD, only one had persistent RV infection. Plasma levels of IL-10 and TNF-α were higher in children with diarrhea compared to uninfected controls but were similar in children with AD and PD. Plasma IFN-γ levels were higher in children who developed PD than in those with AD (P = 0.008) or uninfected controls (P = 0.001). In stools, the levels of TNF-α, the only cytokine detected, were similar in the three groups of children. RV-specific immunoglobulin G (IgG) titers in plasma were higher in uninfected children than in those with AD (P < 0.001) or PD (P = 0.024) but titers were similar in children with AD and PD. RV-specific IgA titers in plasma and stool were similar in the three groups of children. From all observed parameters, only elevated plasma IFN-γ levels were associated with subsequent development of PD. However, a larger sample size is necessary to substantiate this observation.

Protective effects and immunomodulation on piglets infected with rotavirus following resveratrol supplementation

“…Cytokines after viral infection has important implications for induction of protective immunity. The immune response of children who developed persistent diarrhea following RV infection established that the concentrations of plasma IL-10 and IFN-γ were higher in children with diarrhea compared to uninfected ones [ 51 ]. Another previous study showed that cytokines, including IFN-γ, IL-6 and IL-10, played a key role in RV infection and protection against RV disease in children [ 52 ].…”

Rotavirus Antagonizes Cellular Antiviral Responses by Inhibiting the Nuclear Accumulation of STAT1, STAT2, and NF-κB

“…It has been demonstrated that TNF-␣ can synergize with type I and II IFN to produce an elevated antiviral state (4,22). As TNF levels are elevated in the serum and stools of rotavirus-infected children (1,29), blocking NF-B nuclear accumulation also might prevent the antiviral action of TNF-␣ in infected cells.…”

Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

“…Sera obtained from infants at 6 and 18 weeks of age were shipped on dry ice from Bangladesh to the Centers for Disease Control in Atlanta, USA for neutralizing antibody assays for poliovirus serotype 1, 2, and 3 (log 2 based titer) which were performed according to World Health Organization methods [16] . Rotavirus plasma IgA was measured as described previously [17] . OPV seroconversion was defined as both a week 18 neutralizing antibody titer greater than 2.83 (log 2 based titer) and a change in the log titer between weeks 6 and 18 of at least 3 (to account for decay in maternally-transferred antibody from week 6 to week 18 with a half-life of 4 weeks).…”