Role of non-polio enterovirus infection in pediatric hemolytic uremic syndrome

Abstract

Verocytotoxin-producing Escherichia coli(VTEC) infections cause most cases of hemolytic uremic syndrome (HUS); 10-30% of patients, however, are negative for VTEC infection. The etiology of HUS in VTEC-negative cases remains poorly understood. Before the association between VTEC infection and HUS was recognized, sporadic cases of HUS with enterovirus infection were reported in the literature. Since May 1988, most cases of HUS in Italy have been reported to the Italian surveillance system, and in 73% of these, evidence of VTEC infection was demonstrated. The aim of this study was to determine whether the frequency of enteroviral infections was different in the acute phase of VTEC-positive and VTEC-negative HUS. Eighty-nine patients were investigated for enteroviral infection, of whom 58 were VTEC positive and 31 VTEC negative. Two serum samples from each patient were examined for seroconversion to enterovirus (coxsackie, echovirus, and picornavirus) by a complement fixation test. Serological evidence of acute infection with non-polio enterovirus was found in 33 patients (37%) [20/58 (34.5%) VTEC positive and 13/31 (41.9%) VTEC negative]. There was no statistically significant difference between the two groups. These results demonstrate that there are no significant differences for enteroviral infection in VTEC-positive and VTEC-negative patients and, therefore, enteroviral infections should not be considered a cause of HUS in VTEC-negative children.

A case of lethal enteroviral haemolytic uraemic syndrome?

“…Our case indicates that enteroviral infections may be able to inflict HUS, and contradicts other studies of HUS [ 3 ].…”

“…Our case underlines the need for a large-scale epidemiological investigation of STEC-negative HUS cases using the most recent sensitive diagnostic tests especially considering the poorer prognosis of STEC-negative cases [ 3 ].…”

“…The main aetiological culprit is Shiga-like toxin-producing E. coli (STEC) accounting for ∼85% of HUS cases. Recently the aetiological role of enteroviruses in HUS has been studied and rejected as being an aetiological agent [ 3 ] even though earlier case reports suggested a role (see references in [ 3 ]). We present a case of HUS, which was probably due to enteroviral infection.…”

“…In support of our conclusion, enteroviruses are known to be able to infect colonic cells and endothelial cells, and damage both by either lytic or immunological mechanisms, the prerequisites for inducing HUS [ 4,5 ]. Furthermore our detection techniques are more sensitive [ 6,7 ] than the ones used earlier in studies [ 3 ].…”

Haemolytic uraemic syndrome

“…Haemolytic uraemic syndrome is classified as postinfectious, complement-mediated, which may be hereditary and/or autoimmune, or associated with other co-existing conditions such as pregnancy, human immunodeficiency virus (HIV) infection, transplantation (bone marrow and solid organ), malignancy, autoimmune diseases, drugs, malignant hypertension as well as other more unusual associations, some of which are hereditary ( Table 1). There is also some degree of overlap between aetiologies; for example, pregnancy- Shigella dysenteriae type 1 [231] Citrobacter freundii [232] Streptococcus pneumoniae Neuraminidase producing [193] Influenza A H1N1 Neuraminidase producing (possible explanation) [192] Enteroviruses Coxsackie A and B, Echo Unclear association [233] HIV [234] Pseudomonas aeruginosa Neuraminidase producing (possible explanation) [235] Complement dysregulation Genetic Mutations in genes encoding for factor H, factor I, MCP, C3, factor B, clusterin, thrombomodulin Resulting in dysregulated complement activation via the alternative pathway [55,154] Rearrangements or deletions in genes encoding complement factor H-related proteins Associated with antibodies to factor H [156] Factor H CFH-H3 and MCP ggaac risk haplotypes [156,161] Acquired Anti-factor H antibodies Associated with genetic rearrangements or deletions in factor H-related proteins [169] Monoclonal gammopathy [236] Mutations in diacylglycerol kinase-e (DGKE)…”