Only 3 participants older than 4 years had pathogens detected in stool either in culture or by direct microscopy. All 3 were boys: Escherichia coli with FC 44.2 mg/kg, age 4 years; hookworm with FC 21.5 mg/kg, age 5.4 years; and Giardia intestinalis with FC 203.4 mg/kg, age 4.5 years. Two children had experienced nosebleeds within the 2 weeks preceding the study: an 11.2-year-old girl with FC 45.3 mg/kg and an 8.2-year-old boy with FC 99.1 mg/kg.
This is the first survey of FC concentrations in an HIV-infected population in sub-Saharan Africa. Children older than 4 years had a higher median FC concentration than the reference values suggested in the literature. Children with more advanced disease had the highest FC concentrations. FC was detectable in all of the children regardless of age, clinical staging of HIV, and CD4 cell percentage. HIV-infected children had more variability in concentrations of FC compared with immunocompetent subjects.
To the best of our knowledge, FC concentrations in HIV-infected patients have been reported only in 1 Italian study of asymptomatic adults (25). FC was >50 mg/mL in 27 of 53 HIV-infected patients, and the authors argue that this is clearly indicative of GI inflammation and that it confirms a breakdown of the intestinal barrier. In our study, a similar proportion (34/59 HIV-infected children) had FC >50 mg/mL, and gut inflammation in these children is likely. Schwartz et al (26) have shown in vitro that neutrophils from HIV-infected people have a diminished inhibitory response to calprotectin. We have shown that children with low CD4 cell count and malnourished children produce calprotectin and present with significantly higher levels. Schwartz et al investigated “asymptomatic” HIV-infected people and we have studied hospitalised children at all of the stages of HIV, which may make comparisons difficult. We have shown that HIV-infected children have more variability in FC than healthy children, and so it is a good tool to follow gut involvement in HIV. The findings of more variability in FC values and an increased median value compared with healthy children, but not as high as seen in children with IBD, may be explained by the effect of HIV on the gut itself with increased permeability, which, again, is linked to microbial translocation (14). More investigations are needed to determine whether FC can be used to monitor the degree of microbial translocation in HIV-infected humans. Increased intestinal permeability in HIV-infected populations has been confirmed by several studies (36–38). Sharpstone et al (38) used a lactulose/L-rhamnose test and showed that all of the HIV-infected participants, except those defined as “well,” had a significantly increased intestinal permeability compared with healthy controls. In our study, we found that children with a low CD4 cell percentage had significantly higher concentrations of FC than those with a high CD4 cell percentage. We argue that participants in our study with a low CD4 cell percentage can be compared with those in the Sharpstone et al study defined as all other than those being “well with HIV,” and that those children with a low CD4 cell percentage had a more advanced enteropathy.
FC is a marker for GI inflammation, frequently used in diagnosis and follow-up of patients with IBD (20–22), and a marker for disease activity in individuals (40). We hypothesise that FC in HIV-infected patients can be used, as in patients with IBD, to follow disease activity in individuals and to investigate gut engagement in HIV-infected children in low-income countries where other, more sophisticated methods are not available. We believe that inflammation in the gut measured by FC may be a good marker in combination with CD4 cell percentage to decide on further investigations and treatment with HAART in children living with HIV.
FC can be used as a marker of GI inflammation in HIV-infected people. HIV-infected children older than 4 years had a median FC concentration above the reference values given in the literature. Children with more advanced disease had increased FC concentrations regardless of age.
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