MultiTest V.1.2, a program to binomially combine independent tests and performance comparison with other related methods on proportional data

<p>Abstract</p> <p>Background</p> <p>Combining multiple independent tests, when all test the same hypothesis and in the same direction, has been the subject of several approaches. Besides the inappropriate (in this case) Bonferroni procedure, the Fisher's method has been widely used, in particular in population genetics. This last method has nevertheless been challenged by the SGM (symmetry around the geometric mean) and Stouffer's <it>Z</it>-transformed methods that are less sensitive to asymmetry and deviations from uniformity of the distribution of the partial <it>P</it>-values. Performances of these different procedures were never compared on proportional data such as those currently used in population genetics.</p> <p>Results</p> <p>We present new software that implements a more recent method, the generalised binomial procedure, which tests for the deviation of the observed proportion of <it>P</it>-values lying under a chosen threshold from the expected proportion of such <it>P</it>-values under the null hypothesis. The respective performances of all available procedures were evaluated using simulated data under the null hypothesis with standard <it>P</it>-values distribution (differentiation tests). All procedures more or less behaved consistently with ~5% significant tests at <it>α </it>= 0.05. Then, linkage disequilibrium tests with increasing signal strength (rate of clonal reproduction), known to generate highly non-standard <it>P</it>-value distributions are undertaken and finally real population genetics data are analysed. In these cases, all procedures appear, more or less equally, very conservative, though SGM seems slightly more conservative.</p> <p>Conclusion</p> <p>Based on our results and those discussed in the literature we conclude that the generalised binomial and Stouffer's <it>Z </it>procedures should be preferred and <it>Z </it>when the number of tests is very small. The more conservative SGM might still be appropriate for meta-analyses when a strong publication bias in favour of significant results is expected to inflate type 2 error.</p

Multifaceted Population Structure and Reproductive Strategy in Leishmania donovani Complex in One Sudanese Village

Leishmania species of the subgenus Leishmania and especially L. donovani are responsible for a large proportion of visceral leishmaniasis cases. The debate on the mode of reproduction and population structure of Leishmania parasites remains opened. It has been suggested that Leishmania parasites could alternate different modes of reproduction, more particularly clonality and frequent recombinations either between related individuals (endogamy) or between unrelated individuals (outcrossing) within strongly isolated subpopulations. To determine whether this assumption is generalized to other species, a population genetics analysis within Leishmania donovani complex strains was conducted within a single village. The results suggest that a mixed-mating reproduction system exists, an important heterogeneity of subsamples and the coexistence of several genetic entities in Sudanese L. donovani. Indeed, results showed significant genetic differentiation between the three taxa (L. donovani, L. infantum and L. archibaldi) and between the human or canine strains of such taxa, suggesting that there may be different imbricated transmission cycles involving either dogs or humans. Results also are in agreement with an almost strict specificity of L. donovani stricto sensu to human hosts. This empirical study demonstrates the complexity of population structure in the genus Leishmania and the need to pursue such kind of analyses at the smallest possible spatio-temporal and ecological scales

Candida antifungal drug resistance in sub-Saharan African populations: A systematic review

BACKGROUND: Candida infections are responsible for increased morbidity and mortality rates in at-risk patients, especially in developing countries where there is limited access to antifungal drugs and a high burden of HIV co-infection. OBJECTIVES: This study aimed to identify antifungal drug resistance patterns within the subcontinent of Africa. METHODS: A literature search was conducted on published studies that employed antifungal susceptibility testing on clinical Candida isolates from sub-Saharan African countries using Pubmed and Google Scholar. RESULTS: A total of 21 studies from 8 countries constituted this review. Only studies conducted in sub-Saharan Africa and employing antifungal drug susceptibility testing were included. Regional differences in Candida species prevalence and resistance patterns were identified. DISCUSSION: The outcomes of this review highlight the need for a revision of antifungal therapy guidelines in regions most affected by Candida drug resistance. Better controls in antimicrobial drug distribution and the implementation of regional antimicrobial susceptibility surveillance programmes are required in order to reduce the high Candida drug resistance levels seen to be emerging in sub-Saharan Africa.This study was supported by the Research Office of the University of the Western Cape (project registration no. ScRIRC2012/10/72)