Serum mannose-binding lectin deficiency is associated with cryptosporidiosis in young Haitian children.

BACKGROUND: Mannose-binding lectin (MBL) is a component of the innate immune response and binds microbial surfaces through carbohydrate recognition domains. MBL deficiency may contribute to susceptibility to a variety of infectious diseases, particularly in young children. MBL binds to the Cryptosporidium sporozoite and may be important in resistance to cryptosporidiosis. METHODS: We studied the association of serum MBL levels and cryptosporidiosis in a case-control study of young Haitian children with cryptosporidiosis versus children who were control subjects. RESULTS: Ninety-nine children were enrolled, as follows: 49 children with cryptosporidiosis, 41 healthy controls, and 9 children with diarrhea from other causes. Case children were more malnourished than controls, and 49% had persistent or chronic diarrhea. At enrollment, mean serum MBL levels were markedly lower in children with cryptosporidiosis (P = .002), as was the number of children with an MBL deficiency of < or = 70 ng/mL (P = .005). In multivariate analysis, the association of cryptosporidiosis and MBL deficiency persisted (P = .002; adjusted odds ratio, 22.4), as did the association of cryptosporidiosis with general malnutrition. The subset of children with cryptosporidiosis and MBL deficiency were more likely to be male (P = .025). CONCLUSIONS: MBL may be an important component of innate immune protection against Cryptosporidium infection in young children. Additional studies are necessary to determine whether MBL intestinal losses, deficient epithelial expression, and/or genetic polymorphisms in the MBL gene contribute to MBL deficiency in cryptosporidiosis and other enteric infections in young children.

Lactulose-mannitol intestinal permeability test in children with diarrhea caused by rotavirus and cryptosporidium. Diarrhea Working Group, Peru.

BACKGROUND: The relationship between intestinal permeability and acute secretory diarrheal syndromes caused by rotavirus and Cryptosporidium parvum in infants less than 36 months of age was studied using the lactulose-mannitol excretion assay. METHODS: An oral solution containing 0.4 g/kg lactulose and 0.1 g/kg mannitol was administered to 15 infants with rotavirus, 7 with Cryptosporidium infection and a control group of 7 with secretory diarrhea admitted to the Oral Rehydration Unit of the National Children's Hospital in Lima, Peru. Urinary sugar excretion was measured using an enzymatic spectrophotometric method. The ratio of urinary excretion of lactulose to mannitol was used to measure intestinal mucosal permeability, with higher ratios indicative of increased intestinal permeability. Infants in all three groups were retested 20 days after the initial test. RESULTS: The (mean +/- SE) lactulose:mannitol (L:M) excretion ratios during the acute phase (day 1) of diarrhea in infants with rotavirus or Cryptosporidium and control infants were 0.67 +/- 0.1, 0.76 +/- 0.16, and 0.26 +/- 0.04, respectively. In the convalescent phase (day 20) the ratios were 0.19 +/- 0.02, 0.28 +/- 0.05, and 0.29 +/- 0.07, respectively. Significant reductions in L:M ratios were noted in rotavirus patients between days 1 and 20 (paired t-test; P < 0.01), Cryptosporidium patients between days 1 and 20 (paired t-test; P < 0.05), and between control subjects on day 1 and rotavirus patients on day 1 and Cryptosporidium patients on day 1 (unpaired t-tests; P < 0.05 for both). There were no significant differences in control subjects between days 1 and 20, control subjects and rotavirus patients on day 20, or control subjects and Cryptosporidium patients on day 20. CONCLUSIONS: The results indicate that increased intestinal permeability caused by rotavirus or cryptosporidium infections in Peruvian infants less than 36 months of age is a significant but reversible phenomenon. The temporal relationship observed in the current study and the contribution of such alterations in intestinal mucosal integrity to the burden of diarrheal disease and the development of malnutrition in developing countries is discussed.

Mucosal injury and disruption of intestinal barrier function in HIV-infected individuals with and without diarrhea and cryptosporidiosis in northeast Brazil.

OBJECTIVES: To determine the relative effects of AIDS-related diarrhea with or without cryptosporidiosis and microsporidiosis on intestinal function and injury. METHODS: We studied 40 HIV-infected patients (20 with and 20 without diarrhea) and 13 healthy volunteers, using the differential urinary excretion of ingested lactulose and mannitol as respective markers of barrier disruption and overall villous surface area. We also examined them for fecal leukocytes, lactoferrin, and alpha 1-antitrypsin. Fasting subjects drank test solution containing lactulose (5 g) and mannitol (1 g). Urine was collected for 5 h and tested for sugars by high-performance liquid chromatography with pulsed amperometric detection. RESULTS: HIV-positive patients with diarrhea had a 2.8-fold higher lactulose:mannitol excretion ratio (L:M) than HIV-positive patients without diarrhea (p = 0.01) and 10.4-fold higher than healthy volunteers (p = 0.004). This was accounted for by a 1.5- to 3.1-fold higher rate of lactulose excretion by HIV patients with diarrhea than by those without diarrhea or by healthy volunteers. Mannitol excretion was 32-55% less in patients with diarrhea than in those without diarrhea or in healthy volunteers. Patients with cryptosporidial diarrhea had a nearly 6-fold higher L:M ratio than those without diarrhea (p < 0.001) and nearly 3-fold higher than those with non-cryptosporidial diarrhea (p = 0.02). One patient with microsporidial infection had a nearly 3-fold higher L:M ratio than controls without diarrhea. Alpha 1-Antitrypsin was positive in 40% of HIV-positive patients with cryptosporidial infections and none of 12 HIV-positive patients with non-cryptosporidial diarrhea. Fecal lactoferrin or leukocytes were increased in all HIV patients with diarrhea. CONCLUSION: HIV infection is associated with intestinal dysfunction and injury, even in patients who do not have diarrhea. However, those with diarrhea, especially with cryptosporidiosis or microsporidiosis, have even greater disruption of intestinal barrier function with potentially important nutritional consequences.

PIP: The effects of AIDS-related diarrhea--with and without cryptosporidiosis and microsporidiosis--on intestinal function and injury were studied in 40 AIDS patients and 13 healthy volunteers from Fortaleza, Brazil. The differential urinary excretion of ingested lactulose and mannitol was used as a marker of barrier disruption and overall villous surface area. HIV-infected patients with diarrhea had a 2.8-fold higher lactulose to mannitol excretion ratio than HIV-positive patients without diarrhea and a 10.4-fold higher ratio than healthy volunteers. Moreover, those with crypotosporidial infection had a lactulose to mannitol ratio almost 6-fold greater than those without diarrhea and nearly 3-fold higher than those with non-cryptosporidial diarrhea. This effect involved both decreased mannitol excretion (decreased intestinal absorptive area) and increased lactulose excretion (mucosal barrier disruption). The single patient with microsporidial infection had a nearly 3-fold higher ratio than healthy volunteers. Alpha1-antitrypsin tests were positive in two of five (40%) HIV-positive patients with cryptosporidial infections compared with none of 12 HIV-infected patients with non-cryptosporidial diarrhea. These findings confirm that HIV infection is associated with profound intestinal dysfunction and injury, even in those without diarrhea. Disruption of the intestinal barrier is even greater, however, in HIV-infected patients with cryptosporidial diarrhea, with potential nutritional consequences.