Risk profiling of soil-transmitted helminth infection and estimated number of infected people in South Asia: A systematic review and Bayesian geostatistical Analysis.

BACKGROUND: In South Asia, hundreds of millions of people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura). However, high-resolution risk profiles and the estimated number of people infected have yet to be determined. In turn, such information will assist control programs to identify priority areas for allocation of scarce resource for the control of soil-transmitted helminth infection. METHODOLOGY: We pursued a systematic review to identify prevalence surveys pertaining to soil-transmitted helminth infections in four mainland countries (i.e., Bangladesh, India, Nepal, and Pakistan) of South Asia. PubMed and ISI Web of Science were searched from inception to April 25, 2019, without restriction of language, study design, and survey date. We utilized Bayesian geostatistical models to identify environmental and socioeconomic predictors, and to estimate infection risk at high spatial resolution across the study region. PRINCIPAL FINDINGS: A total of 536, 490, and 410 georeferenced surveys were identified for A. lumbricoides, hookworm, and T. trichiura, respectively. We estimate that 361 million people (95% Bayesian credible interval (BCI) 331-395 million), approximately one-quarter of the South Asia population, was infected with at least one soil-transmitted helminth species in 2015. A. lumbricoides was the predominant species. Moderate to high prevalence (>20%) of any soil-transmitted helminth infection was predicted in the northeastern part and some northern areas of the study region, as well as the southern coastal areas of India. The annual treatment needs for the school-age population requiring preventive chemotherapy was estimated at 165 million doses (95% BCI: 146-185 million). CONCLUSIONS/SIGNIFICANCE: Our risk maps provide an overview of the geographic distribution of soil-transmitted helminth infection in four mainland countries of South Asia and highlight the need for up-to-date surveys to accurately evaluate the disease burden in the region.

Markov Model Predicts Changes in STH Prevalence during Control Activities Even with a Reduced Amount of Baseline Information.

BACKGROUND: Estimating the reduction in levels of infection during implementation of soil-transmitted helminth (STH) control programmes is important to measure their performance and to plan interventions. Markov modelling techniques have been used with some success to predict changes in STH prevalence following treatment in Viet Nam. The model is stationary and to date, the prediction has been obtained by calculating the transition probabilities between the different classes of intensity following the first year of drug distribution and assuming that these remain constant in subsequent years. However, to run this model longitudinal parasitological data (including intensity of infection) are required for two consecutive years from at least 200 individuals. Since this amount of data is not often available from STH control programmes, the possible application of the model in control programme is limited. The present study aimed to address this issue by adapting the existing Markov model to allow its application when a more limited amount of data is available and to test the predictive capacities of these simplified models. METHOD: We analysed data from field studies conducted with different combination of three parameters: (i) the frequency of drug administration; (ii) the drug distributed; and (iii) the target treatment population (entire population or school-aged children only). This analysis allowed us to define 10 sets of standard transition probabilities to be used to predict prevalence changes when only baseline data are available (simplified model 1). We also formulated three equations (one for each STH parasite) to calculate the predicted prevalence of the different classes of intensity from the total prevalence. These equations allowed us to design a simplified model (SM2) to obtain predictions when the classes of intensity at baseline were not known. To evaluate the performance of the simplified models, we collected data from the scientific literature on changes in STH prevalence during the implementation of 26 control programmes in 16 countries. Using the baseline data observed, we applied the simplified models and predicted the onward prevalence of STH infection at each time-point for which programme data were available. We then compared the output from the model with the observed data from the programme. RESULTS: The comparison between the model-predicted prevalence and the observed values demonstrated a good accuracy of the predictions. In 77% of cases the original model predicted a prevalence within five absolute percentage points from the observed figure, for the simplified model one in 69% of cases and for the simplified model two in 60% of cases. We consider that the STH Markov model described here could be an important tool for programme managers to monitor the progress of their control programmes and to select the appropriate intervention. We also developed, and made freely available online, a software tool to enable the use of the STH Markov model by personnel with limited knowledge of mathematical models.

Soil-transmitted helminthiasis: the relationship between prevalence and classes of intensity of infection.

BACKGROUND: Recently, WHO has developed a predictive model to evaluate the impact of preventive chemotherapy programs to control the morbidity of soil-transmitted helminths (STHs). To make predictions, this model needs baseline information about the proportion of infections classified as low, moderate and high intensity, for each of the three STH species. However, epidemiological data available are often limited to prevalence estimates. METHODS: We reanalyzed available data from 19 surveys in 10 countries and parameterized the relationship between prevalence of STH infections and the proportion of moderate and heavy intensity infections. RESULTS: The equations derived allow feeding the WHO model with estimates of the proportion of the different classes of infection intensity when only prevalence data is available. CONCLUSIONS: The prediction capacities of the STH model using the equations developed in the present study, should be tested by comparing it with the changes on STH epidemiological data observed in control programs operating for several years.

Inflammation in rat pups subjected to short hyperthermic seizures enhances brain long-term excitability.

UNLABELLED: Inflammatory processes in response to infection are involved in the pathophysiological mechanisms of febrile seizures (FS). Prolonged FS may promote the development of temporal lobe epilepsy. It has been shown in rats that prolonged hyperthermic seizures (HS) are followed by long-term modification of brain excitability. To examine whether short FS results in modification of brain excitability, we induced an inflammatory response in combination with short HS. METHODS: HS were induced in rat pups at either P11 or P16 using a heating lamp with a continuous monitoring of the core temperature. Rat pups were maintained at the temperature seizure threshold during 5 min. In order to induce an inflammatory response, lipopolysaccharide (LPS, Eschericha coli 055:B5) was injected i.p. at 5 microg/kg or 50 microg/kg, 2h prior seizure induction. After 1 month, pentylenetetrazol threshold (PTZth) was used to assess the change of brain excitability. Histological studies were performed 24h after the FS (Fluorojade-B) and after the PTZth (cresyl violet). RESULTS: The temperature thresholds to induce the seizures were not different among the groups. The PTZth was not significantly different between sham and FS only groups, and decreased dose-dependently when LPS was combined to FS. Histological studies suggested the absence of cell injury. CONCLUSION: Lower PTZth obtained by using LPS in combination with HS in rat pups suggests a change in brain excitability. Our model with only 5 min of HS in combination with LPS suggests that an inflammatory response could, in part, explain long-term change in brain excitability following short FS.

Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet.

The ketogenic diet (KD) and the modified Atkins diet are effective therapies for intractable epilepsy. We compared retrospectively the KD and modified Atkins diet in 27 children and also assessed serum long chain fatty acid profiles. After 3 months, using an intent-to-treat analysis, the KD was more successful, with >50% seizure reduction in 11/17 (65%) vs. 2/10 (20%) with the modified Atkins diet, p=0.03. After 6 months, however, the difference was no longer significant: 7/17 (41%) vs. 2/10 (20%) (p=0.24). We observed a preventive effect of both diets on the occurrence of status epilepticus. After 1 and 3 months of either diet, responders experienced a significant decrease in serum arachidonic acid concentration compared to non-responders. The KD and modified Atkins diet led to seizure reduction in this small pilot series, with slightly better results after 3 months with the KD, but not after 6 months. The decrease of serum arachidonic acid levels might be involved in the anticonvulsive effects of KD or modified Atkins diet.

[Polyunsaturated fatty acids: anticonvulsive effects and underlying mechanisms]. / Acides gras poly-insaturés: propriétés et mécanismes anticonvulsivants.

Omega-3 and omega-6 poly-unsaturated fatty acids (PUFA) are the major families of PUFA that can be found as components of the human diet. After ingestion, both omega-3 and omega-6 PUFA are distributed to every cell in the body where they are involved in a myriad of physiological processes, including regulation of cardiovascular, immune, hormonal, metabolic, neuronal, and visual functions. At the cellular level, these effects are mediated by changes in membrane phospholipids structure, by interference with eicosanoid intracellular signaling, and by regulation of gene expression. The literature suggests the antiepileptic properties of PUFA, although these evidences emerge from basic science rather than from clinical trials. Several hypotheses have been suggested to explain the anticonvulsive effects of PUFA: modification of the membrane fluidity, direct action of PUFA on cell membrane ionic channels and/or receptors, modulation of inflammatory responses. Regarding the published clinical trials, the data are conflicting. It is currently not known whether different doses or different omega-3: omega-6 ratios would be effective.

Anticonvulsant effects of linolenic acid are unrelated to brain phospholipid cell membrane compositions.

PURPOSE: Recent studies have revealed that polyunsaturated fatty acids (PUFAs) have anticonvulsive properties. Clinical trials using PUFAs reported conflicting results. It was suggested that PUFAs have anticonvulsant effects via modifications of brain phospholipids. Moreover, some authors suggested that the effect of the ketogenic diet (KD) leads to a high PUFA content. The aim of the study was to evaluate the anticonvulsant properties of a mixture containing alpha-linolenic acid (ALA) and linolenic acid (LA). METHODS: Four-week-old male Wistar rats were fed one of the following diets for 30 days: KD, standard diet, and standard diet with daily LA/ALA oral supplementation. Pentylenetetrazol (PTZ) threshold was used to assess the anticonvulsive effects of the diets. Nutritional status was monitored by body composition evaluation. Fatty acids composition of both plasma and brain phospholipids were also assessed. RESULTS: Animals fed the KD and those who had the daily LA/ALA supplementation exhibited an increase in PTZ threshold. The animals did not show any modification of body composition or brain phospholipid composition. The plasma fatty acids composition was modified by KD and LA/ALA. A decrease in arachidonic acid (AA) concentrations was observed in both the KD and LA/ALA groups, while an increase in eicosapentanoic acid (EPA) and ALA concentrations was only observed in the LA/ALA group. CONCLUSIONS: Our study shows that LA/ALA supplementation exerts anticonvulsive properties comparable to KD. Nutritional status can not explain the anticonvulsive effects of PUFAs supplementation. Brain phospholipids were not different within groups. The anticonvulsive effects of LA supplementation seem to be unrelated to brain phospholipid composition.

Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, exerts anticonvulsive properties.

The underlying mechanisms of the ketogenic diet (KD) remain unknown. Involvement of peroxisome proliferator-activated receptor-alpha (PPARalpha) has been suggested. The aim of this study was to assess the anticonvulsant properties of fenofibrate, a PPARalpha agonist. Wistar rats were fed at libitum during 14 days by regular diet, KD, regular diet containing 0.2% fenofibrate (F), or KD containing 0.2% fenofibrate (KD + F). Pentylenetetrazol (PTZ) threshold and latencies to the onset of status epilepticus induced by lithium-pilocarpine were used to assess diet treatments with anticonvulsive effects. Myoclonic and generalized seizure PTZ thresholds were increased in F- and KD-treated animals in comparison to control. No difference was observed between KD + F group and the others groups (control, F, KD). Latencies to the onset of status epilepticus were increased in F and KD groups compared to control. Fenofibrate exerts anticonvulsive properties comparable to KD in adult rats using PTZ and lithium-pilocarpine models. The underlying mechanisms such as PPARalpha activation and others should be investigated. These findings may provide insights into future directions to simplify KD protocols.