Leishmaniasis in the era of tumor necrosis factor alpha antagonist therapy--a research agenda for Europe.

A number of published case reports suggest an association of tumor necrosis factor (TNF) alpha antagonist use and manifest leishmaniasis. Despite increasing popularity of antagonising TNF alpha for the treatment of autoimmune disorders, systematic research on the risk of opportunistic leishmaniasis in patients receiving these drugs is lacking. This perspective identifies areas of uncertainty regarding the safety profile of TNF alpha antagonist drugs and their clinical use in patients at risk of leishmaniasis. Then, we reflect on how current pharmacovigilance activities in Europe could be enhanced to help reduce these uncertainties. Our aim is to stimulate a debate about this important drug safety issue with potential consequences for patients receiving TNF alpha antagonists living in or travelling to areas endemic for leishmaniasis.

Malnutrition in young children of rural Burkina Faso: comparison of survey data from 1999 with 2009.

OBJECTIVE: For measurement of progress towards the Millennium Development Goal (MDG) 1, reliable data on nutrition indicators of specific countries are essential. Malnutrition is also the main determinant for childhood mortality, which is addressed in MDG 4. METHODS: In the health and demographic surveillance area of Kossi Province in north-western Burkina Faso, nutritional parameters were compared in two cohorts of young children of the same age range from eight villages. Surveys took place in June and December of the year 1999 and 2009. A multivariate model was used to control for confounding variables. RESULTS: For the 1999 study, data were analysed for 179 and 197 children who took part in the June and December survey respectively. In 2009, corresponding data were analysed for 460 and 409 children. Prevalence of underweight was highest in December 1999 (42.6%) and lowest in December 2009 (34.1%). After adjustment for age, sex and village, there was a slight but not always significant improvement in the z-scores of weight-for-age, weight-for-length, length-for-age, and mid-arm circumference over time. CONCLUSIONS: The findings from this study confirm the still unacceptable high prevalence of malnutrition in young children of rural sub-Saharan Africa (SSA). Progress in the reduction of malnutrition remains slow on this continent making it rather unlikely that the corresponding MDGs will be achieved. Large-scale multi-sectoral community-based interventions are urgently needed for a sustainable improvement of child health in SSA.

Tumor necrosis factor alpha antagonist drugs and leishmaniasis in Europe.

Leishmaniasis is endemic in Europe and the prevalence of latent infection in the Mediterranean region is high. Reports describing opportunistic leishmaniasis in European patients treated with tumor necrosis factor (TNF) alpha antagonist drugs are rapidly accumulating. For other granulomatous infections, risk of opportunistic disease varies by mode of TNF-alpha antagonism. This study explores whether this may also be the case for leishmaniasis. We ascertained the relative frequency of exposure to different TNF antagonist drugs among published cases of opportunistic leishmaniasis in Europe and compared this with the prescription of these drugs in Europe. We found that risk of opportunistic leishmaniasis is higher in patients receiving anti-TNF monoclonal antibodies (infliximab or adalimumab) compared with patients treated with the TNF-receptor construct etanercept. Clinicians may want to consider these observations, which suggest that etanercept should be favoured over anti-TNF monoclonal antibodies in individuals living in or visiting areas endemic for leishmaniasis until evidence from prospective research is available. A European adverse event reporting system is required to identify rare opportunistic infections associated with immunosuppressive and immunomodulatory biotherapies.

Is the wealth index a proxy for consumption expenditure? A systematic review.

BACKGROUND: Many epidemiological studies require a measure of socioeconomic position. The monetary measure preferred by economists is consumption expenditure; the wealth index has been proposed as a reliable, simple alternative to expenditure and is extensively used. METHODS: A systematic review was conducted of the agreement between wealth indices and consumption expenditure, summarising the agreement and exploring factors affecting agreement. RESULTS: Seventeen studies using 36 datasets met the inclusion criteria. Of these, 22 demonstrated weak agreement, 10 moderate agreement, and four strong agreement. There was some evidence that agreement is higher: in middle-income settings; in urban areas; for wealth indices with a greater number of indicators; and for wealth indices including a wider range of indicators. CONCLUSIONS: The wealth index is mostly a poor proxy for consumption expenditure.

h-sgk serine-threonine protein kinase as transcriptional target of p38/MAP kinase pathway in HepG2 human hepatoma cells.

The human serum and glucocorticoid dependent serine/threonine kinase h-sgk has previously been discovered as cell volume regulated gene. The present study has been performed to elucidate the involvement of p38-kinase in the transcriptional control of h-sgk by osmotic cell shrinkage. The p38-kinase has previously been cloned as the mammalian homologue of HOG1 kinase, which constitutes a part of the osmosensor in the yeast Saccharomyces cerevisiae. Phosphorylated (active) p38-kinase has been estimated with Western blotting, transcription of hsgk using Northern blotting. Both, increase of extracellular NaCl concentration by 50 mmol/l and addition of 10 micromol/l anisomycin increase phosphorylation of the p38-kinase within 5 to 10 minutes. h-sgk transcription is upregulated by addition of 50 mmol/l NaCl and by anisomycin (10 micromol/l), effects completely inhibited by the specific p38-kinase inhibitor, SB 203580 (10 micromol/l). In conclusion, the stimulation of h-sgk transcription by osmotic cell shrinkage is mediated by p38-kinase.