Infection and Co-infection with Helminths and Plasmodium among School Children in C?te d’Ivoire: Results from a National Cross-Sectional Survey

Background

Helminth infection and malaria remain major causes of ill-health in the tropics and subtropics. There are several shared risk factors (e.g., poverty), and hence, helminth infection and malaria overlap geographically and temporally. However, the extent and consequences of helminth-Plasmodium co-infection at different spatial scales are poorly understood.

Methodology

This study was conducted in 92 schools across Côte d’Ivoire during the dry season, from November 2011 to February 2012. School children provided blood samples for detection of Plasmodium infection, stool samples for diagnosis of soil-transmitted helminth (STH) and Schistosoma mansoni infections, and urine samples for appraisal of Schistosoma haematobium infection. A questionnaire was administered to obtain demographic, socioeconomic, and behavioral data. Multinomial regression models were utilized to determine risk factors for STH-Plasmodium and Schistosoma-Plasmodium co-infection.

Principal Findings

Complete parasitological and questionnaire data were available for 5,104 children aged 5-16 years. 26.2% of the children were infected with any helminth species, whilst the prevalence of Plasmodium infection was 63.3%. STH-Plasmodium co-infection was detected in 13.5% and Schistosoma-Plasmodium in 5.6% of the children. Multinomial regression analysis revealed that boys, children aged 10 years and above, and activities involving close contact to water were significantly and positively associated with STH-Plasmodium co-infection. Boys, wells as source of drinking water, and water contact were significantly and positively associated with Schistosoma-Plasmodium co-infection. Access to latrines, deworming, higher socioeconomic status, and living in urban settings were negatively associated with STH-Plasmodium co-infection; whilst use of deworming drugs and access to modern latrines were negatively associated with Schistosoma-Plasmodium co-infection.

Conclusions/Significance

More than 60% of the school children surveyed were infected with Plasmodium across Côte d’Ivoire, and about one out of six had a helminth-Plasmodium co-infection. Our findings provide a rationale to combine control interventions that simultaneously aim at helminthiases and malaria.     

Bayesian Risk Mapping and Model-Based Estimation of Schistosoma haematobium–Schistosoma mansoni Co-distribution in C?te d′Ivoire

Background

Schistosoma haematobium and Schistosoma mansoni are blood flukes that cause urogenital and intestinal schistosomiasis, respectively. In Côte d′Ivoire, both species are endemic and control efforts are being scaled up. Accurate knowledge of the geographical distribution, including delineation of high-risk areas, is a central feature for spatial targeting of interventions. Thus far, model-based predictive risk mapping of schistosomiasis has relied on historical data of separate parasite species.

Methodology

We analyzed data pertaining to Schistosoma infection among school-aged children obtained from a national, cross-sectional survey conducted between November 2011 and February 2012. More than 5,000 children in 92 schools across Côte d′Ivoire participated. Bayesian geostatistical multinomial models were developed to assess infection risk, including S. haematobium–S. mansoni co-infection. The predicted risk of schistosomiasis was utilized to estimate the number of children that need preventive chemotherapy with praziquantel according to World Health Organization guidelines.

Principal Findings

We estimated that 8.9% of school-aged children in Côte d′Ivoire are affected by schistosomiasis; 5.3% with S. haematobium and 3.8% with S. mansoni. Approximately 2 million annualized praziquantel treatments would be required for preventive chemotherapy at health districts level. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection is of little importance across the country.

Conclusions/Significance

We provide a comprehensive analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d′Ivoire and a strong empirical basis for a rational targeting of control interventions.     

Research into the (Cost-) effectiveness of the ketogenic diet among children and adolescents with intractable epilepsy: design of a randomized controlled trial

Background  

Epilepsy is a neurological disorder, characterized by recurrent unprovoked seizures which have a high impact on the individual as well as on society as a whole. In addition to the economic burden, epilepsy imposes a substantial burden on the patients and their surroundings. Patients with uncontrolled epilepsy depend heavily on informal care and on health care professionals. About 30% of patients suffer from drug-resistant epilepsy. The ketogenic diet can be a treatment of last resort, especially for children. The beneficial effect of the ketogenic diet has been proven, but information is lacking about its cost-effectiveness. In the current study we will evaluate the (cost-) effectiveness of the ketogenic diet in children and adolescents with intractable epilepsy.     

Plasmodium sensitivity to artemisinins: magic bullets hit elusive targets

Artemisinins are efficacious antimalarial drugs widely employed as first-line treatment in endemic countries under the form of combined therapies. Different molecular modes of action have been postulated to explain the parasiticidal effect of these compounds; however, none has been unequivocally accepted, and their physiological relevance is still questioned. Similarly, no definite genetic determinant of Plasmodium sensitivity to artemisinins has been identified so far. A better understanding of the mode of action of artemisinins and the genetic basis of laboratory-induced or field-observed altered susceptibility is crucial for malaria control. In this review different models of artemisinins' molecular action are briefly presented, focusing on recent advances, and the evidence of potential association between various gene polymorphisms and artemisinin resistance is comprehensively reviewed.     

Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus

Introduction  

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients.     

Pharmacokinetic, biodistribution, and biophysical profiles of TNF nanobodies conjugated to linear or branched poly(ethylene glycol)

Covalent attachment of poly(ethylene glycol) (PEG) to therapeutic proteins has been used to prolong in vivo exposure of therapeutic proteins. We have examined pharmacokinetic, biodistribution, and biophysical profiles of three different tumor necrosis factor alpha (TNF) Nanobody-40 kDa PEG conjugates: linear 1 × 40 KDa, branched 2 × 20 kDa, and 4 × 10 kDa conjugates. In accord with earlier reports, the superior PK profile was observed for the branched versus linear PEG conjugates, while all three conjugates had similar potency in a cell-based assay. Our results also indicate that (i) a superior PK profile of branched versus linear PEGs is likely to hold across species, (ii) for a given PEG size, the extent of PEG branching affects the PK profile, and (iii) tissue penetration may differ between linear and branched PEG conjugates in a tissue-specific manner. Biophysical analysis (R(g)/R(h) ratio) demonstrated that among the three protein-PEG conjugates the linear PEG conjugate had the most extended time-average conformation and the most exposed surface charges. We hypothesized that these biophysical characteristics of the linear PEG conjugate accounts for relatively less optimal masking of sites involved in elimination of the PEGylated Nanobodies (e.g., intracellular uptake and proteolysis), leading to lower in vivo exposure compared to the branched PEG conjugates. However, additional studies are needed to test this hypothesis.     

Inactivation of Salmonella enterica by UV-C Light Alone and in Combination with Mild Temperatures

The aim of this investigation was to study the efficacy of the combined processes of UV light and mild temperatures for the inactivation of Salmonella enterica subsp. enterica and to explore the mechanism of inactivation. The doses to inactivate the 99.99% (4D) of the initial population ranged from 18.03 (Salmonella enterica serovar Typhimurium STCC 878) to 12.75 J ml⁻¹ (Salmonella enterica serovar Enteritidis ATCC 13076). The pH and water activity of the treatment medium did not change the UV tolerance, but it decreased exponentially by increasing the absorption coefficient. An inactivating synergistic effect was observed by applying simultaneous UV light and heat treatment (UV-H). A less synergistic effect was observed by applying UV light first and heat subsequently. UV did not damage cell envelopes, but the number of injured cells was higher after a UV-H treatment than after heating. The synergistic effect observed by combining simultaneous UV and heat treatment opens the possibility to design combined treatments for pasteurization of liquid food with high UV absorptivity, such as fruit juices.     

Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations

Introduction

Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity.

Methods

The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies.

Results

Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4.

Conclusion

Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation.     

The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study

Introduction

The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).

Methods

This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly.

Results

After three years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician''s global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life.

Conclusions

Three years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS, in addition to the currently used more subjective measures.     

A comparison of vertebral muscle fiber characteristics between human and monkey tissue

A comparison has been made of the vertebral muscle fiber characteristics between human and rhesus monkey. The main purpose of the experiment was to assess the value of the monkey as an animal model for the study of idiopathic scoliosis involving vertebral muscle influence. Vertebral muscle samples were collected from both clearly defined superficial and deep sites on both sides of the column in the midlumbar region. The material was subjected to routine histological and histochemical techniques. The results show considerable similarities between the deep muscle samples of the two species, but the superficial muscles are significantly different on most of the measurements made.