Child mortality, defined here as mortality under age five, is not evenly distributed but found in clusters. In a contemporary polygamous population in Ghana with extended families, we separate... Show moreChild mortality, defined here as mortality under age five, is not evenly distributed but found in clusters. In a contemporary polygamous population in Ghana with extended families, we separate clustering at the parental and household levels, which are often overlapping and inseparable in other historical studies. For eight years, we followed 28,994 individuals, including 9,288 children under the age of five, in 1,703 households. We identified four determinants that had a significant effect on child mortality: sex of the child, age of the child, drinking source, and socioeconomic status. After correcting for these determinants, we still identified significant clustering of child mortality at the level of the village (covariance [cov] = 0.02, p = .04), household (cov = 0.14, p = .003), father (cov = 0.24, p = .001), and mother (cov = 0.18, p = .05). The present data provide clues regarding the levels at which to look for unidentified determinants of child mortality and suggest that the importance of the father could be larger than previously thought. Show less
Boef, A.G.C.; May, L.; Bodegom, D. van; Lieshout, L. van; Verweij, J.J.; Maier, A.B.; ... ; Eriksson, U.K. 2012
According to the hygiene hypothesis, reduced exposure to infections could explain the rise of atopic diseases in high-income countries. Helminths are hypothesised to alter the host's immune... Show moreAccording to the hygiene hypothesis, reduced exposure to infections could explain the rise of atopic diseases in high-income countries. Helminths are hypothesised to alter the host's immune response in order to avoid elimination and, as a consequence, also reduce the host responsiveness to potential allergens. To elucidate the effect of current helminth infections on immune responsiveness in humans, we measured cytokine production in a rural Ghanaian population in an area with multiple endemic parasites including malaria, intestinal helminths and protozoa. Multiplex real-time PCR in stool samples was used for the detection of four gastrointestinal helminths, of which only Necator americanus was commonly present. A similar assay was used to test for Giardia lamblia in stool samples and malaria infection in venous blood samples. Levels of the cytokines interleukin (IL)-10, tumour necrosis factor (TNF)-α, IL-17, IL-6, IL-13, and interferon (IFN)-γ were determined in whole-blood samples ex vivo-stimulated either with lipopolysaccharide (LPS) and zymosan (for innate cytokine production) or the T-cell mitogen phytohaemagglutinin (PHA). There were no significant differences in either innate or PHA-stimulated cytokine production dependent on current N. americanus infection. Plasmodium falciparum malarial infection was associated with a pro-inflammatory response indicated by increased innate production of TNF-α, IL-17 and IL-6. There was no clear pattern in cytokine responses dependent on G. lamblia-infection. In conclusion, in this rural Ghanaian population current N. americanus infections are not associated with altered immune function, while infection with P. falciparum is associated with pro-inflammatory innate immune responses. Show less
Boef, A.G.C.; May, L.; Bodegom, D. van; Kuningas, M.; Eriksson, U.K.; Westendorp, R.G.J. 2012
Interleukin-10 (IL-10) production is under tight genetic control in populations living in affluent environments. However, little is known about the role of IL10 genetics on cytokine production in... Show moreInterleukin-10 (IL-10) production is under tight genetic control in populations living in affluent environments. However, little is known about the role of IL10 genetics on cytokine production in populations living in environments with high infectious pressure. We have previously reported that, in a rural Ghanaian population, the most common IL10 haplotype associates with a pro-inflammatory response. Here, we aim to replicate these findings in an independent sample of the same population 2 years later. IL-10 and tumour necrosis factor-α (TNF-α) protein concentrations were determined in whole-blood samples ex vivo stimulated with lipopolysaccharide and zymosan in 2006 (n=615) and 2008 (n=647). The association between IL10 single nucleotide polymorphisms and Z-scores of IL-10 and TNF-α levels was analysed in each population subset. The most common IL10 haplotype was associated with a significantly lower IL-10 production and nonsignificantly increased TNF-α levels. The correlation between repeated cytokine assays, based on 111 individuals with measurements in both 2006 and 2008, was r=0.53 (P<0.001) for IL-10 and r=0.36 (P<0.001) for TNF-α. The replication of our previously found effect of variation in the IL10 gene on IL-10 production and the correlation between repeated cytokine stimulation assays provide evidence that IL10 genetics have an important role in regulating the host response under high infectious pressure.Genes and Immunity advance online publication, 11 August 2011; doi:10.1038/gene.2011.57. Show less
