Childhood Cryptosporidiosis Is Associated with a Persistent Systemic Inflammatory Response

Abstract

Cryptosporidiosis in young children prompts local inflammation in the intestinal tract. We studied a cohort of young children with cryptosporidiosis to determine whether systemic inflammatory responses occur and, if so, to evaluate whether inflammation persists after infection. Cryptosporidiosis was associated with increased levels of interleukin-8 and tumor necrosis factor- alpha systemically, which persisted at 6 months after enrollment. The level of intestinal tumor necrosis factor- alpha was elevated at enrollment, but elevated levels did not persist. Worsening of malnutrition, particularly stunting, was observed after infection. The association of cryptosporidiosis, inflammation, and stunting in children with cryptosporidiosis warrants further evaluation.

Lymphoproliferative and Cytokine Responses to Cryptosporidium parvum in Patients Coinfected with C. parvum and Human Immunodeficiency Virus

“…This is in agreement with an earlier study (14) which reported higher levels of IL-10 and IFN-␥ in HIV-seronegative patients with a history of cryptosporidiosis but comparatively low levels of IL-10 and no production of IFN-␥ in healthy individuals. In contrast, other reports have failed to detect IFN-␥ in cryptosporidiosis patients' PBMCs in response to Cryptosporidium (19,20). In the present study, no significant difference was observed in the cytokine responses to Cryptosporidium between immunosuppressed and immunocompetent individuals infected with Cryptosporidium.…”

Intestinal Immune Response to HumanCryptosporidiumsp. Infection

“…However, we identified IFN-␥ in the intestines of a minority of volunteers only after Cryptosporidium challenge, and IFN-␥ expression was limited to the volunteers who appeared to be immune (that is, either seropositive or resistant to a challenge with a dose that was greater than the dose that would infect most volunteers) (93). Other groups failed to detect IFN-␥ in stools or stimulated PBMC obtained at the time of acute infection (29,44,45). Thus, while IFN-␥ seems to be critical for the memory response, other mechanisms may play a larger role in resolution of acute infection.…”

“…Similarly, increased CXCL-8 levels were found in the stools of Cryptosporidium-infected Haitian children compared to controls (44,45). Also, peripheral blood mononuclear cells (PBMC) of infected Haitian children expressed higher levels of CXCL-8 when they were restimulated in vitro up to 6 months after infection (45). In a study of Brazilian children, more stool samples containing elevated levels of IL-8 came from control children than from infected children (3).…”

“…This finding suggests that Cryptosporidium induced an intestinal inflammatory response. The stools of infected Haitian and Brazilian children had markedly elevated levels of the receptor for the proinflammatory cytokine tumor necrosis factor alpha (TNF-␣) (3,44,45). TNF-␣ is believed to be involved in recruiting inflammatory cells to the intestinal mucosa (27,50).…”

“…TNF-␣ is believed to be involved in recruiting inflammatory cells to the intestinal mucosa (27,50). PBMC of infected Haitian children expressed higher levels of TNF-␣ up to 6 months after infection when they were restimulated in vitro, suggesting that cryptosporidiosis triggers a systemic immune response which may lead to enhanced inflammation and possibly be responsible for worsening of malnutrition and stunting (45).…”