Helicobacter pylori and faecal calprotectin in apparently healthy and HIV-infected Ugandan children
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Abstract Gastrointestinal dysfunction, often presenting as diarrhoea, is one of the major causes of morbidity and mortality among children in low-income countries. It is estimated that 56% of child deaths were attributable to malnutrition's potentiating effects in children living in lowincome countries. There are numerous gastrointestinal problems in children in low-income countries, in particularly in human immunodeficiency virus (HIV) infected children. The gastrointestinal tract is the largest immunological site of the body and HIV infection profoundly impacts on gut function and disease development. Most studies of the gastrointestinal function in patients in low-income countries have been performed among adults. The objectives of this thesis are: 1) to examine the prevalence of H. pylori in apparently healthy urban Ugandan children and in HIV-infected, highly active anti-retroviral therapy (HAART) naïve children in the same geographical area, and 2) to examine if a faecal marker for gut inflammation, faecal calprotectin, can be used in children in a low-income country living in poor sanitary conditions, and if the marker can be used in an HIV-infected population. Two surveys were conducted in urban Kampala, Uganda. The first was community-based, in children aged 0-12 years, and conducted by door-to-door visits in a neighbourhood characterised by slum-like living conditions. The second survey was hospital-based at the Department of Paediatrics and Child Health, Mulago National Referral Hospital, Kampala where all HIV-infected, HAART naïve children admitted were invited to participate. A questionnaire was used in both surveys to address questions about medical conditions and socio-economic factors. Faeces were examined for H. pylori by using a rapid monoclonal antigen test. Faecal calprotectin was analysed using the ELISA technique. The overall prevalence of H. pylori antigen in apparently healthy urban Ugandan children aged 0-12 years was 44.3%. Early colonization was common with 28.7% in children younger than 1 year of age. There was a steady increase with age (1<3 years 46.0%, 3<6 years 51.7%, and 6<9 years 54.8%). Children living in permanent houses had a significantly lower colonization rate (38.5%) compared to those living in semi-permanent houses, 48.6%. HIV-infected children had a lower overall prevalence (22.5%). Age specific prevalence’s were; 14.7% in infants 0<1 year, 30.9% among toddles 1<3 years, and 20.7% for children 3<12 years. HIV-infected children more seriously affected by their disease (lower CD4 cell percentage or WHO clinical stage II-IV) were less likely to be colonized with H. pylori. Median faecal calprotectin concentrations in apparently healthy Ugandan children were comparable to those found in children living in high-income countries. They were 249mg/kg in infants 0<1 year (n=54), 75mg/kg among toddlers 1<4 years (n=89), and 28mg/kg for children 4<12 years (n=159). There was no significant difference in faecal calprotectin concentration when considering the education of female caretaker, wealth index, gender, habits of using mosquito nets, being colonized with H. pylori or having other pathogens in the stool. In the HIV-infected children, median faecal calprotectin concentrations were different from those in apparently healthy children. They were 208mg/kg in infants 0<1 year, 171mg/kg among toddlers 1<4 years, and 62mg/kg for children 4<12 years. HIV-infected children more seriously affected by their disease (lower CD4 cell percentage) or diarrhoea at enrolment had a higher median faecal calprotectin concentration. In conclusion, H. pylori colonization among apparently healthy urban Ugandan children is common at an early age and increases with age. The prevalence among HIV-infected children in the same geographical area is only about half. Faecal calprotectin is also a marker for gut inflammation that is well suited for use also in children in low-income countries, with the same cut-off values as suggested for children living in high-income countries. Faecal calprotectin can also be used as a tool also in an HIV-infected population for evaluation of gut inflammation. We found calprotectin to be higher in those HIVinfected children with more advanced disease, regardless of age.
Paper I: Hestvik E, Tylleskar T, Kaddu-Mulindwa DH, Ndeezi G, Grahnquist L, Olafsdottir E, Tumwine JK. Helicobacter pylori in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based cross sectional survey. BMC Gastroenterology 10:62, June 2010. The article is available at: http://hdl.handle.net/1956/4677Paper II: Hestvik E, Tumwine J.K, Tylleskar T, Grahnquist L, Ndeezi G, Kaddu-Mulindwa DH, Aksnes L, Olafsdottir E. Faecal calprotectin concentrations in apparently healthy children aged 0-12 years in urban Kampala, Uganda: a community-based survey. BMC Pediatrics 11:9, February 2011. The article is available at: http://hdl.handle.net/1956/5484Paper III: Hestvik E, Tylleskar T, Ndeezi G, Grahnquist L, Olafsdottir E, Tumwine J.K, Kaddu- Mulindwa DH. Prevalence of Helicobacter pylori in HIV-infected, HAART naïve Ugandan children: a hospital-based survey. Journal of the International AIDS Society 14:34, June 2011. The article is available at: http://hdl.handle.net/1956/5559Paper VI: Hestvik E, Olafsdottir E, Tumwine J.K, Tylleskar T, Ndeezi G, Kaddu-Mulindwa DH, Aksnes L, Grahnquist L. Faecal calprotectin in HIV-infected HAART naïve Ugandan children: a hospital-based survey. In press. Full text not available in BORA due to publisher restrictions. The article is available at: http://dx.doi.org/10.1097/MPG.0b013e318241a683