Deep Peroneal Nerve: Orientation and Branching at the Ankle and Proximal Part of the Foot

Objective: This study investigated the frequency and types of 1) orientation of the deep peroneal nerve (DPN) and its branches relative to the dorsalis pedis artery (DPA) and the extensor hallucis longus tendon (EHLT) and 2) branching site and pattern of DPN at the distal area of leg and the proximal zone of the foot. Materials and Methods: One-hundred and sixty specimens from the lower extremities of 80 formalin-embalmed cadavers were investigated for anatomical position, orientation and the branching pattern of DPN by manual dissection, starting from the anterior side of lower extremity just proximal to ankle joint down to the area distal to inferior extensor retinaculum. Results: The most prevalent medial-to-lateral orientation of structures in the area anterior to ankle joints was the EHLT/DPA/DPN. Comparing DPA with the branching of DPN in the areas inside anterior tarsal tunnel (ATT) and distal to ATT, the most common type was an orientation of DPA that was lateral to both the DPN main trunk and its medial terminal branch. Regarding branching sites and patterns of DPN in the intermalleolar and ATT areas, nearly half of the studied specimens had DPN bifurcation at the intermalleolar level and more than half of the bifurcations were inside the ATT. Conclusion: This study establishes novel data regarding type variation and prevalence of DPN in areas of ankle and proximal part of foot in the Thai population which could be helpful in clinical practice

Heritability of P. falciparum and P. vivax Malaria in a Karen Population in Thailand

The majority of studies concerning malaria host genetics have focused on individual genes that confer protection against rather than susceptibility to malaria. Establishing the relative impact of genetic versus non-genetic factors on malaria infection and disease is essential to focus effort on key determinant factors. This relative contribution has rarely been evaluated for Plasmodium falciparum and almost never for Plasmodium vivax. We conducted a longitudinal cohort study in a Karen population of 3,484 individuals in a region of mesoendemic malaria, Thailand from 1998 to 2005. The number of P. falciparum and P. vivax clinical cases and the parasite density per person were determined. Statistical analyses were performed to account for the influence of environmental factors and the genetic heritability of the phenotypes was calculated using the pedigree-based variance components model. The genetic contribution to the number of clinical episodes resulting from P. falciparum and P. vivax were 10% and 19% respectively. There was also moderate genetic contribution to the maximum and overall parasite trophozoite density phenotypes for both P. falciparum (16%&16%) and P. vivax (15%&13%). These values, for P. falciparum, were similar to those previously observed in a region of much higher transmission intensity in Senegal, West Africa. Although environmental factors play an important role in acquiring an infection, genetics plays a determinant role in the outcome of an infection with either malaria parasite species prior to the development of immunity

Genetic Determination and Linkage Mapping of Plasmodium falciparum Malaria Related Traits in Senegal

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10−4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved

Number of pairs of individuals as defined by genetic relationship (phi2) and household relationship.

<p>Number of pairs of individuals as defined by genetic relationship (phi2) and household relationship.</p

Contribution (%) of genetic (heritability, h²) and house (c²) effects to variability in malaria and non-malaria clinical and biological phenotypes of <i>P. falciparum</i> (Pf) and <i>P. vivax</i> (Pv).

<p>h², variance due to genetics, c², variance due to house effect, S.E. the standard error; NS, not significant (<i>p-value</i>>0.05); NE, not estimated.</p>a<p>Retained because of marginal significance.</p

Pair-wise correlation between phenotypes studied.

<p>PFA, Number of visits Pf+; NMF, Number of non-malaria fever visits; PVA, Number of visits Pv+; mx-PFD, Pf max parasite density; PFD, Overall Pf parasite densities; mx-PVD, Pv max parasite density; PVD, Overall Pv parasite densities. In bold, highly significant p value (≤10⁻⁴); in italic, significant p value that becomes not significant after Bonferroni correction for multiple testing (21 hypotheses tested).</p

Proportions of variation explained by genetic heritability, house and environmental factors found to have a significant effect on the phenotype measured (Table 3&6).

<p>(A) Number of clinical episodes of <i>P. falciparum</i> (PFA); (B) Number of clinical episodes of <i>P. vivax</i> (PVA); (C) Number of non-malaria clinical episodes (NMF); (D) Maximum <i>P. falciparum</i> parasite density (mx-PFD); (E) Overall <i>P. falciparum</i> parasite density (PFD); (F) Maximum <i>P. vivax</i> parasite density (mx-PVD); (G) Overall <i>P. vivax</i> parasite density (PVD). Values of 1% or less not indicated numerically in the figure.</p

Family statistics.

<p>Family statistics.</p

Summary of samples used in epidemiological and genetic analyses.

<p>For epidemiological analyses, presented are the number of data points (observations and calculated mean/max values) analyzed for each phenotype category, the corresponding number of individuals implicated and hence residual values generated. For genetic analyses, presented are the number of these individuals for whom pedigree information was available and thus the number of independent families and relative pairs count for each phenotype in the heritability analyses. In parentheses, the number belonging to the large complex family.</p

A variant in the CD209 promoter is associated with severity of dengue disease.

Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells. Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 x 10(-7)) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 x 10(-6)). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies