The association between child Schistosoma spp. infections and morbidity in an irrigated rice region in Mali: a localized study

Schistosomiasis is one of the neglected tropical diseases endemic to Mali. There has been insufficient investigation of the morbidity burden in highly endemic irrigated rice areas with the ongoing mass drug administration with praziquantel. In February 2005, a year after an initial mass drug administration in 2004, we performed the first cross-sectional survey of schistosomiasis in the Kokry-Bozo village in the Office du Niger rice irrigation region. In the fourteen years since this survey, there has been almost no research into schistosomiasis morbidity in Mali due to lack of funding. Therefore, the 2005 survey supplies near-baseline data for any future research into the treatment impacts in the area

A Comparative Study of the Spatial Distribution of Schistosomiasis in Mali in 1984–1989 and 2004–2006

Geostatistical maps are increasingly being used to plan neglected tropical disease control programmes. We investigated the spatial distribution of schistosomiasis in Mali prior to implementation of national donor-funded mass chemotherapy programmes using data from 1984–1989 and 2004–2006. The 2004–2006 dataset was collected after 10 years of schistosomiasis control followed by 12 years of no control. We found that national prevalence of Schistosoma haematobium and S. mansoni was not significantly different in 2004–2006 compared to 1984–1989 and that the spatial distribution of both infections was similar in both time periods, to the extent that models built on data from one time period could accurately predict the spatial distribution of prevalence of infection in the other time period. This has two main implications: that historic data can be used, in the first instance, to plan contemporary control programmes due to the stability of the spatial distribution of schistosomiasis; and that a decade of donor-funded mass distribution of praziquantel has had no discernable impact on the burden of schistosomiasis in subsequent generations of Malians, probably due to rapid reinfection

Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease

We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population

Importance of Non-Selective Cation Channel TRPV4 Interaction with Cytoskeleton and Their Reciprocal Regulations in Cultured Cells

BACKGROUND: TRPV4 and the cellular cytoskeleton have each been reported to influence cellular mechanosensitive processes as well as the development of mechanical hyperalgesia. If and how TRPV4 interacts with the microtubule and actin cytoskeleton at a molecular and functional level is not known. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the interaction of TRPV4 with cytoskeletal components biochemically, cell biologically by observing morphological changes of DRG-neurons and DRG-neuron-derived F-11 cells, as well as functionally with calcium imaging. We find that TRPV4 physically interacts with tubulin, actin and neurofilament proteins as well as the nociceptive molecules PKCepsilon and CamKII. The C-terminus of TRPV4 is sufficient for the direct interaction with tubulin and actin, both with their soluble and their polymeric forms. Actin and tubulin compete for binding. The interaction with TRPV4 stabilizes microtubules even under depolymerizing conditions in vitro. Accordingly, in cellular systems TRPV4 colocalizes with actin and microtubules enriched structures at submembranous regions. Both expression and activation of TRPV4 induces striking morphological changes affecting lamellipodial, filopodial, growth cone, and neurite structures in non-neuronal cells, in DRG-neuron derived F11 cells, and also in IB4-positive DRG neurons. The functional interaction of TRPV4 and the cytoskeleton is mutual as Taxol, a microtubule stabilizer, reduces the Ca2+-influx via TRPV4. CONCLUSIONS AND SIGNIFICANCE: TRPV4 acts as a regulator for both, the microtubule and the actin. In turn, we describe that microtubule dynamics are an important regulator of TRPV4 activity. TRPV4 forms a supra-molecular complex containing cytoskeletal proteins and regulatory kinases. Thereby it can integrate signaling of various intracellular second messengers and signaling cascades, as well as cytoskeletal dynamics. This study points out the existence of cross-talks between non-selective cation channels and cytoskeleton at multiple levels. These cross talks may help us to understand the molecular basis of the Taxol-induced neuropathic pain development commonly observed in cancer patients

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

Circulating anodic and cathodic antigen in serum and urine of mixed Schistosoma haematobium and S. mansoni infections in Office du Niger, Mali

In Office du Niger, an area endemic for both Schistosoma haematobium and S. mansoni in Mali, circulating anodic (CAA) and cathodic (CCA) antigen detection assays were performed on pretreatment serum and urine samples from two villages, Rigandé and Siguivoucé, and compared with egg counting methods. The highest prevalence was obtained with the urine-CCA assay which also had the highest sensitivity to S. haematobium, S. mansoni or mixed infection. A single urine-CCA assay was as sensitive as repeated egg counts (one stool+two urine examinations per individual). When the different assays were tested in parallel, several combinations including assays on serum were found to be highly sensitive. As urine sampling is widely accepted, urine assays will be used for further monitoring these villages one and two years after chemotherapy

Assessment of cure by detection of circulating antigens in serum and urine, following schistosomiasis mass treatment in two villages of the Office du Niger, Mali

Eight weeks after mass chemotherapy with 40 mg/kg praziquantel in two villages in Office du Niger (an irrigation area in Mali, endemic for both Schistosoma haematobium and Schistosoma mansoni) the circulating anodic (CAA) and cathodic (CCA) antigen detection assays were carried out on serum and urine samples. Both prior and post treatment highest prevalence was measured with the urine-CCA assay. Cure rates determined by antigen detection were almost half that of the egg counting methods. It was shown that the reduction in intensity should be preferentially assessed by the serum-CAA assay. Compared with egg detection, a single antigen detection assay gave a much better assessment of the impact of chemotherapy. PIP: Surveys conducted in different regions of Mali, to compare the circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) detection assays with the classical method of parasitologic egg counting in the diagnosis of schistosomiasis, found the highest sensitivity with the urine CCA assay. The present study investigated cure rates in a mixed Schistosoma haematobium/S. mansoni endemic area by applying the CAA and CCA assays on 97 serum and urine specimens from Dogon, Mali. 8 weeks after mass treatment with 40 mg/kg of praziquantel, the cure rate was 87% according to 2 urine egg counts and 96% as determined by a single stool egg count. Both before and after treatment, the highest prevalence was again measured by the urine CCA assay. Cure rates determined by antigen detection were almost one-half that of the egg counting method. Reduction in intensity, as determined by serum CAA concentrations, was above 90% in both villages in the study area. The urine CCA assay, however, showed a reduction in intensity in one site and an increase in the other. These results suggest that the serum CAA assay should be used preferentially to assess the reduction in intensity, since serum antigen levels reflect worm burdens more directly than those in urine, given their influence by renal excretion dynamics. Timing of cure rate determination by using antigen detection should take into account local transmission patterns