Achievements and challenges of lymphatic filariasis elimination in Sierra Leone

BackgroundLymphatic filariasis (LF) is targeted for elimination in Sierra Leone. Epidemiological coverage of mass drug administration (MDA) with ivermectin and albendazole had been reported >65% in all 12 districts annually. Eight districts qualified to implement transmission assessment survey (TAS) in 2013 but were deferred until 2017 due to the Ebola outbreak (2014–2016). In 2017, four districts qualified for conducting a repeat pre-TAS after completing three more rounds of MDA and the final two districts were also eligible to implement a pre-TAS.Methodology/Principal findingsFor TAS, eight districts were surveyed as four evaluation units (EU). A school-based survey was conducted in children aged 6–7 years from 30 clusters per EU. For pre-TAS, one sentinel and one spot check site per district (with 2 spot check sites in Bombali) were selected and 300–350 persons aged 5 years and above were selected. For both surveys, finger prick blood samples were tested using the Filariasis Test Strips (FTS).For TAS, 7,143 children aged 6–7 years were surveyed across four EUs, and positives were found in three EUs, all below the critical cut-off value for each EU. For the repeat pre-TAS/pre-TAS, 3,994 persons over five years of age were surveyed. The Western Area Urban had FTS prevalence of 0.7% in two sites and qualified for TAS, while other five districts had sites with antigenemia prevalence >2%: 9.1–25.9% in Bombali, 7.5–19.4% in Koinadugu, 6.1–2.9% in Kailahun, 1.3–2.3% in Kenema and 1.7% - 3.7% in Western Area Rural.Conclusions/SignificanceEight districts in Sierra Leone have successfully passed TAS1 and stopped MDA, with one more district qualified for conducting TAS1, a significant progress towards LF elimination. However, great challenges exist in eliminating LF from the whole country with repeated failure of pre-TAS in border districts. Effort needs to be intensified to achieve LF elimination.     

Rice Resistance to Brown Spot Mediated by Nitrogen and Potassium

This study was undertaken to investigate the effects of both nitrogen (N) and potassium (K) rates on rice resistance to brown spot, caused by the fungus Bipolaris oryzae. Rice plants (cultivar ‘Metica 1’) were grown in soil corrected with 0, 25, 50, 75 and 100 mg of N / kg (as NH₄NO₃) of soil as well as with 25, 50, 75, 125 and 150 mg of K / kg (as KCl) of soil. Thirty‐three‐day‐old plants were inoculated with a suspension of Bipolaris oryzae conidia and the incubation period (IP), number of lesions (NL) per cm² of leaf area and disease severity was evaluated. Disease severity was scored at 24, 48, 72, 96, 120 and 144 h after inoculation and data were used to obtain the area under brown spot progress curve (AUBSPC). Soil plant analysis development (SPAD) index, plant dry weight and concentration of N and K in leaf tissues were also determined for both non‐inoculated (NI) and inoculated (IN) plants. Concentration of N in leaf tissue increased as the N rates in the soil increased. Concentration of K in leaf tissue increased sharply as the K rates in the soil increased for both NI and IN plants. Concentration of K in leaf tissue was not affected by N rates. The IP increased as the N rates increased, but was somewhat less impacted by increasing K rates. The NL decreased as the N rates increased. The NL dramatically declined at the highest K rates. The AUBSPC dramatically declined as the N and K rates in the soil increased. SPAD index values increased as the N and K rates in the soil increased for both NI and IN plants. Plant dry weight increased as the N and K rates in the soil increased for both NI and IN plants. Results from this study suggest that combining high N and K rates may contribute to reducing the intensity of brown spot in rice while improving plant development.     

Defective attachment of dermatosparactic fibroblasts to collagens I and IV

Attachment of fibroblasts from dermatosparactic sheep and cattle to collagenous substrates (types I and IV) is defective (30-50%) when compared with fibroblasts from normal or heterozygous animals. The difference was independent of the amount of substrate, incubation time and protein synthesis. No differences were observed in the binding to fibronectin or laminin. Reduced attachment to collagen can be partially restored by adding fibronectin. The polygonal morphology of dermatosparactic cells was, however, not altered by attachment and growth on dishes coated with different collagens or fibronectin. Reduced interaction with collagens could be due to changes in specific receptors and may represent a further pathological change in dermatosparactic animals.     

Autocrine Production of Insulin-like Growth Factor-I (IGF-I) Affects Paracellular Transport Across Epithelial Cells In Vitro

Autocrine production of growth factors can have significant effects on cell activity. We report for the first time that autocrine production of insulin-like growth factor-I (IGF-I) alters paracellular transport across bovine mammary epithelial cells in vitro. Paracellular transport was assessed by measuring phenol red transport across mammary alveolar cells-large T antigen (MAC-T cells) derived from parental mammary epithelial cells, cultured on porous membranes and compared with two different transfected MAC-T cell lines that constitutively secrete IGF-I. Phenol red transport was essentially blocked in parental cell culture after six days, while IGF-I secreting cells provided essentially no barrier. Surprisingly, neither co-culture studies between parental and IGF-I-secreting cells nor addition of exogenous IGF-I or IGF-binding protein-3 reversed the phenol red transport properties. IGF-I-secreting cells did however express lower levels of the junction components occludin and E-cadherin than parental cells, suggesting that localized autocrine IGF-I activity might lead to increased permeability via changes in both the tight and adherens junction protein levels.     

Modulation of cellular biosynthetic activity in the retracting collagen lattice

When included in a free floating collagen lattice, several types of cells and fibroblasts attach to the collagen polymers, retract the gel, and their biosynthetic activity is repressed. Under similar conditions transformed pulmonary epithelial rat (PER) cells are unable to attach to the fibers and to significantly retract the lattice. Retraction can be induced by adding fibronectin (fn) and factor XIII (FXIII) together. This effect is fibronectin dose dependent and observed with a maximum efficiency for FXIII concentrations of 0.1 U/ml and above. Fibronectin or FXIII alone has only a limited effect on retraction. This experimental model allowed us to study the biosynthetic activity of PER cells under various degrees of cell interaction (control less than FXIII less than fn less than fn + FXIII) with their three-dimensional collagen support. The more the cells interacted with their support and retracted the gel, the more protein and collagen synthesis were reduced. This effect was observed for the products deposited in the cell layer and for those released in the medium. Increasing collagen concentration in a nonretracting lattice to a final density obtained in a maximally retracted lattice resulted in a much lower repression of biosynthetic activity. Fn and FXIII added at the same concentrations in monolayer cultures did not produce significant modification in biosynthetic activities. We propose that the regulation of the biosynthetic activity of adherent cells contracting the lattice is related to mechanical information resulting from the interactions between the cells and their support.     

Community-wide prevalence and intensity of soil-transmitted helminthiasis and Schistosoma mansoni in two districts of Sierra Leone

In Sierra Leone, nationally powered school-based surveys have documented significant progress in the control of soil-transmitted helminthiasis (STH) and schistosomiasis. In order to assess the district-level prevalence and intensity of infection among key at-risk groups outside of school age children (SAC), we conducted a multi-stage, cluster-sample household survey in Bo and Kenema districts in May 2018. From both districts, we examined 1,282 pre-school age children (PSAC), 730 school age children (SAC), and 517 adults over 14 years (including 387 women of reproductive age, or WRA) for STH and Schistosoma mansoni infection using Kato Katz technique. In Bo, STH prevalence was 8.0% (95% Upper Confidence Limit 10.2%) in PSAC, 6.4% (95% Upper Confidence Limit 9.0%) in SAC, 14.1% (95% Upper Confidence Limit 17.4%) in all adults and 11.9% (95% Upper Confidence Limit 17.4%) in WRA. In Kenema, STH prevalence was 18.1% (95% Upper Confidence Limit 20.5%) in PSAC, 17.3% (95% Upper Confidence Limit 20.7%) in SAC, and 16.9% (95% Upper Confidence Limit 20.5%) in all adults and 16.9% (95% Upper Confidence Limit 22.6%) in WRA. Hookworm species were the most prevalent of STH in both districts overall. The overall prevalence of S. mansoni was <10% in Bo and <20% in Kenema, and was similar across age groups. No moderate or heavy intensity STH infections or heavy intensity S. mansoni infections, as per World Health Organization (WHO) classification, were detected in either district. Sanitation variables, such as toilet access and quality, were independently associated with STH and S. mansoni infection. In Kenema, STH prevalence in SAC was within the WHO-defined range for annual treatment, whereas a previous nationally-powered survey estimated it to lie within the range of treatment once per two years. By utilizing community-based sampling, we were able to assess prevalence among WRA and make recommendations based on current guidance from WHO. To continue toward elimination of STH and S. mansoni as a public health problem, resources should be mobilized to increase access to and uptake of improved sanitation at community and household levels.     

Combined spatial prediction of schistosomiasis and soil-transmitted helminthiasis in Sierra Leone: a tool for integrated disease control

Background

A national mapping of Schistosoma haematobium was conducted in Sierra Leone before the mass drug administration (MDA) with praziquantel. Together with the separate mapping of S. mansoni and soil-transmitted helminths, the national control programme was able to plan the MDA strategies according to the World Health Organization guidelines for preventive chemotherapy for these diseases.

Methodology/Principal Findings

A total of 52 sites/schools were selected according to prior knowledge of S. haematobium endemicity taking into account a good spatial coverage within each district, and a total of 2293 children aged 9–14 years were examined. Spatial analysis showed that S. haematobium is heterogeneously distributed in the country with significant spatial clustering in the central and eastern regions of the country, most prevalent in Bo (24.6% and 8.79 eggs/10 ml), Koinadugu (20.4% and 3.53 eggs/10 ml) and Kono (25.3% and 7.91 eggs/10 ml) districts. By combining this map with the previously reported maps on intestinal schistosomiasis using a simple probabilistic model, the combined schistosomiasis prevalence map highlights the presence of high-risk communities in an extensive area in the northeastern half of the country. By further combining the hookworm prevalence map, the at-risk population of school-age children requiring integrated schistosomiasis/soil-transmitted helminth treatment regimens according to the coendemicity was estimated.

Conclusions/Significance

The first comprehensive national mapping of urogenital schistosomiasis in Sierra Leone was conducted. Using a new method for calculating the combined prevalence of schistosomiasis using estimates from two separate surveys, we provided a robust coendemicity mapping for overall urogenital and intestinal schistosomiasis. We also produced a coendemicity map of schistosomiasis and hookworm. These coendemicity maps can be used to guide the decision making for MDA strategies in combination with the local knowledge and programme needs.     

Importance of correlation between gene expression levels: application to the type I interferon signature in rheumatoid arthritis

Background

The analysis of gene expression data shows that many genes display similarity in their expression profiles suggesting some co-regulation. Here, we investigated the co-expression patterns in gene expression data and proposed a correlation-based research method to stratify individuals.

Methodology/Principal Findings

Using blood from rheumatoid arthritis (RA) patients, we investigated the gene expression profiles from whole blood using Affymetrix microarray technology. Co-expressed genes were analyzed by a biclustering method, followed by gene ontology analysis of the relevant biclusters. Taking the type I interferon (IFN) pathway as an example, a classification algorithm was developed from the 102 RA patients and extended to 10 systemic lupus erythematosus (SLE) patients and 100 healthy volunteers to further characterize individuals. We developed a correlation-based algorithm referred to as Classification Algorithm Based on a Biological Signature (CABS), an alternative to other approaches focused specifically on the expression levels. This algorithm applied to the expression of 35 IFN-related genes showed that the IFN signature presented a heterogeneous expression between RA, SLE and healthy controls which could reflect the level of global IFN signature activation. Moreover, the monitoring of the IFN-related genes during the anti-TNF treatment identified changes in type I IFN gene activity induced in RA patients.

Conclusions

In conclusion, we have proposed an original method to analyze genes sharing an expression pattern and a biological function showing that the activation levels of a biological signature could be characterized by its overall state of correlation.