Estelle Guerry
email: estelle.guerry@laplace.univ-tlse.fr

Cătălin Daniel Gălățanu

Laurent Canale

Georges Zissis
email: georges.zissis@laplace.univ-tlse.fr

Optimizing the luminous environment using DiaLUX software at "Constantin and Elena" Elderly House -Study Case

Keywords: Adapted environment, Elderly visual aquity, Lighting simulations, Luminance contrast, Retirement home's interior design

The spatial and luminous optimization of the living environment of the elderly is now a major problem, reflecting the growing desire to meet their needs. It's common to design efficient lighting environments through the use of specialized design software, using standard parameters. The design of a lighting system for elderly today shakes up these habits. It modifies the design parameters and requires specific new parameters, meeting their specific needs. This non-hypothetical and different design process was tested here through a case study in a retirement home. It will develop a type of design based on contrast of luminance against illuminance ratio, leading to the development of a guide to good practice, thanks to which the CAD had to have a substantially better performance with DIALux Evo. Expanding even further the lighting design and accuracy of details, an original approach based on MATLAB functions are demonstrated.

Introduction

The prevalence of visual pathologies increases with age. In fact, nearly 25% of over 75 years old suffer from a visual pathology [START_REF] Moroszlay | La vision des personnes âgées en EMS[END_REF]. In addition, according to OMS, 54% of people living in retirement homes have proven visual pathologies [START_REF] Mp. Christiaen | Voir en EMS : Etude sur présence des déficits visuels dans la population âgées vivant en EMS[END_REF].

Increasingly, this increasing prevalence is taken into account in the design of the built environment, but when this isn't the case, the environment becomes a source of handicap [START_REF] Felix | De la vision au projet : Nouvelles construction, agrandissement ou rénovation d'un EMS[END_REF], increase the risk of falls. They are then multiplied by two in a situation of multiple pathologies [START_REF] Marks | Falls Among the Elderly and Vision : A Narrative Review[END_REF]. It also becomes complicated to practice the acts of daily life autonomously and safely [START_REF]Lighting your way to better vision[END_REF]. The finding is the same when it comes to moving, action sometimes requiring assistance when the elderly can't find their bearings, or poorly located in their environment [START_REF] Bell | Visual Deficits in the Elderly[END_REF]. Adapting the visual environment to the vision of the elderly is a necessity, which helps to prevent the risk of confusion, disorientation by improving their perception of their living environment. Physiological aging, such as a decrease in the diameter of the pupil, and pathological changes in the eye, such as cataracts, thus generate particular lighting needs in the elderly.

Quantity and quality of light, spatial optimization and contrasts are all singular parameters to take into account in their entirety in order to propose a lighting system adapted to their visual acuity and also comfortable [START_REF] Mr | Reduced visual acuity in elderly people : the role of ergonomics and gerontechnology[END_REF]. It's then essential to design a luminous environment taking into consideration these particularities and specific needs. This will include improved lighting, between natural and artificial lighting, a better distribution of this lighting, between ambient lighting and additional lighting, a decrease in glare, alternating brightness and a suppression of light reflections, an amplification of contrasts, in particular with the help of colors or an increase in the contours of objects, an arrangement of spaces giving rise to a sense of security by reducing or even removing obstacles and offering spatial references, through a choice coating in line with the design of the lighting system [START_REF] Mp | Vivre mieux dans un environnement adapté, Lumières, contrastes et repères au service des personnes âgées en EMS[END_REF].

As part of an interior design, the light design and its current applications can be optimized here by using specialized software. Considering here the new parameters inherent to the visual needs of the elderly, the use of this digital tool offers us the possibility of designing an adapted and intelligent luminous implantation [START_REF] Fh | Color and Light in Man-made Environments[END_REF].

The classical method limitations for interior lighting design

Our work on designing a lighting system adapted to the visual needs of the elderly is based on a case study in the Constantin and Elena retirement home, Iasi, Romania. It was chosen for its impersonal chromatic character and not adapted to the particular visual needs of the elderly occupying the premises. Indeed, the wall coverings are white and immaculate, thus presenting no contrasts or spatial references. We have chosen to apply the classical methodology inherent to the use of the DIALux EVO 8 software, specialized in the design of interior lighting systems. This is a design work that matches the design of a lighting system intended for the average observer. But we have also added the new design parameters that will provide an appropriate lighting design for the elderly user with visual disturbances such as skirting boards, door frames and other structural architectural elements. Thanks to the integration of these new parameters of the modeling phase to the interpretation of the results, we are able to propose a design process differentiating the usual design systems.

Starting from the usual lighting design, the approach is very simple and without specific requirements. Based on EN 12464-1 and -2, the illuminance ratio, uniformity, glare limitation are calculated for the working plane. The results are presented in Fig. 1, where the working plane in the pathway. There are some situation when this minimal requirements are extended. A typical situation is an exhibition hall, when the horizontal illuminance on the wall is relevant for visibility. In DIALux EVO is possible to obtain these results, as in Fig. 2: Fig. 2. The extended design for interior lighting system, including horizontal illuminance in lux for the walls.

For the study case, some supplementary visual task are necessary to be identify and study. One of them is the door visibility, seen as a pathway but also like an obstacle. In DIALux EVO is possible to introduce the door in the lighting simulation, with some particular parameters (material, texture, color) and to obtain some results, as in Fig. 3. The main problem is the absence of the specific details from the door, because only some predefined doors are available, including the frame. To increase the fidelity of the simulations, particular objects could be created, using "extrusion body", useful for our case. In Fig. 4 is presented such detail, scalable as in reality (working m or mm in respect with the real door):

Even some results are available, also for luminance distribution (with average values, maximum and minimum values), the luminance contrast available for the frame of the door is difficult to be evaluated. Increasing the fineness of the calculation grid could be a solution, as presented in Fig. 5: Fig. 5. The increasing the fineness of the calculation grid gives better resolution for illumination distribution, but no satisfactory information about the contrast of luminance.

In conclusion, luminance contrast is difficult to be evaluated, because DIALux EVO, as EN 12464, don't take in consideration different connected surfaces, when the luminance variance become important. Because the assessment of luminance contrast for different spatial object is important for elderly to avoid falling or injuries, an original approach for this kind of details is proposed, using MATLAB.

Luminance contrast assessment using MATLAB simulations

The main issue is to demonstrate the difference between the lighting design based on illuminance (as EN 12464) and the assessment of luminance, especially the contrast of luminance. The MATLAB model is built only for a detail from the interior of the building, respectively the frame of the door (or a step, stairs, handrail). The model is based on the frame profile, 15 cm deep, with a rounded edge with 4 cm radius, as in Fig. 6: After this fast 2D validation, a 3D mesh-grid was generated, including reflexivity of the materials, as in Fig. 7: Fig. 7. The spatial model of the door frame (dimensions in cm), and the left corner is at (0, 0, 0), with color-map for materials reflexivity.

Using original MATLAB functions, illuminance ratio (lx) could be calculated. These functions are based on calculating the form factors between the various finite surfaces obtained from mesh-generation. The light flux with direct incidence from the source is then reflected between the various surfaces until it is considered complete attenuation. In order to maximize the visual effect of the luminance (to which the eye is sensitive) compared with illuminance ratio (to which the eye is indirect sensitive), a light source was impose with 3D symmetrical light intensity of 500 cd, situated at the coordinates (x= 2.60; y= -0.9; z= 0.4), related on Fig. 6 and Fig. 7. The results relative to illuminance ratio are displayed with MATLAB function surf, as in Fig. 8:

The door

The wall The frame The traffic

A B C D E F
These illuminance map is easy to be accepted, due to the incident angle of the lighting that is close to normal for DE region from Fig. 7 and tangential for EF region. To highlight the differences between the lighting design based on illuminance ratio and lighting design based on luminance contrast, the illuminance variance on the longitudinal (horizontal) profile of the door is extracted in Fig. 9:

Fig. 9. The illuminance variance (lx) on the median line of the frame model (as in Fig. 7), plotted for the elements (40, 1:106) from the total matrix of illuminance.

The next step, luminance assessment, is presented in Fig. 10, assuming that the surfaces of the door and wall are perfect diffuse (Lambertian):

Fig. 10. The luminance variance (lx) on the median line of the frame model (as in Fig. 7), plotted for the elements (40, 1:106) from the total matrix of illuminance (as Fig. 8).

We notice that the differences between Fig. 9 and Fig. 10 are huge, concluding that the peak in illuminance is not mandatory to be present as luminance. In fact, the luminance contrast between the frame and the door is very poor, much less than 0.7, which is the threshold for visibility. This could be observed in Fig. 11, generated for the luminance ratio. The comparison between Fig. 10 and Fig. 11 gives a supplementary argument: even if the frame is well illuminated (zone DE in Fig. 9), lighting incidence being optimal, close to normal (as a particular case), the luminance will be lower, due the color and reflectivity of the paintings. The result is sensitive to the particular lighting scene, a different light distribution could generate total different luminance contrast. This observation make the DIALux simulation more important. The possibility to build models in details generates more accurate assessment of the pathway visibility.

Discussion

The results obtained here show that it's possible to obtain lighting solutions adapted to the needs of elderly users through the use of light design software usually used for applications intended for the average observer. The comfort and quality of life of the elderly are among the main concerns of our European societies, for example in France [START_REF] Economy | Definition. Site of the actor of the silver eco, industrial sector supported by the French government[END_REF], these results will constitute a guide of good practice, in adequacy with the expected and desires of the users but also of the policies in force [START_REF]French Ministries of Solidarity and Health, Improve the quality of care and support in institutions. Site of the French Ministries of Solidarity and Health [Online[END_REF].

This guide to unheard of good practices can be made available to the authorities to facilitate its development and deployment in retirement homes as a first step. Indeed, it will be possible for the future to be considered and reworked to match the needs and expectations of a home life. Contrary to the usual practices of architects, our new approach of DIALux and MATLAB makes possible the modeling of a prototype of the final space and also the quantitative evaluation of the luminous characteristics, and in particular the contrast of luminance, major characteristic in the discrimination of the environment [START_REF] Kutas | Luminance contrast and chromaticity contrast preference on the colour display for young and elderly users[END_REF] [START_REF] Owsley | Anging and low-contrast vision : face perception[END_REF].

The difference between lighting design based on illumination level and luminance contrast can be schematized as follows:

Classical This approach is thus of great use for the designer, in order to understand the complexity of the light design, correlated to the particular needs of elderly users. It's also useful for the investors, as well as the authorities in order to be able to improve the living conditions of the elderly.

Conclusion

Thanks to our differentiating approach to the use of DIALux interior lighting system design software, we are able to design lighting systems adapted to the visual needs of elderly users, here based on the study of retirement home "Constantin and Elena" from Iaşi, Romania. The integration of new parameters allows us to extract luminance contrast from the conventional design approach. By shaping digital design systems, it's possible to develop specific installations. It also justifies the immediate interventions necessary to optimize the building to improve the visual comfort of the elderly, thus constituting a model for many other retirement homes.

Fig. 1 .

 1 Fig. 1. The classical design for interior lighting system, with vertical illuminance in lux for the working plane.

Fig. 3 .

 3 Fig. 3. Details about the horizontal illuminance on calculation object (door).

Fig. 4 .Fig. 6 .

 46 Fig. 4. Building the frame of the door (with "extrusion object") on the left, and illuminance in lux on the calculation object (right).

Fig. 8 .

 8 Fig. 8. The illuminance ratio (lx) obtained from a source with spherical light intensity of 500 cd, situated at the coordinates in m (x= 2.60; y= -0.9; z= 0.4).

Fig. 11 .

 11 Fig. 11. The luminance map (cd/m 2 ) for the illuminance ratio from Fig.8, revealing the poor luminance contrast and lower visibility for the door frame.

  design based on illumination level: • Visual activities and visual tasks for the room are determined • Establish working plans and the necessary lighting level • Lighting design with consideration of aesthetic and visual comfort • Check the illumination pattern on the working plane Design by luminance and by luminance contrast: • Design the complete configuration for the illumination level • Continue checking the visibility threshold for access ways • The extreme limits position of the observer is established (there may be also elderly people who move autonomously but in the trolley) • Directions and travel flows (arrival / departure, left or right) • Obstacles and boundaries of the pathways (railings, stairs, doors, windows) • Set design elements that generate luminance contrast • Perform the luminaires solutions and check the visibility threshold • Luminous contrast is enhanced by design details and additional light sources in the day, night or twilight hypothesis, or even emergency evacuation.


Prof Jean-Louis Pujol
email: jl-pujol@chu-montpellier.fr

Laurent Greillier

Clarisse Audigier-Valette

Denis Moro-Sibilot

Lionel Uwer

José Hureaux

Florian Guisier

Delphine Carmier

Jeannick Madelaine

Josiane Otto

Valérie Gounant

Patrick Merle

Pierre Mourlanette

Olivier Molinier

Aldo Renault

Audrey Rabeau

Martine Antoine

Marc G Denis

Sebastien Bommart

Alexandra Langlais

Franck Morin

Pierre-Jean Souquet

A Randomized Non-Comparative Phase II Study of Anti-Programmed Cell Death-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients With Small Cell Lung Cancer: Results From the IFCT-1603 Trial

Keywords: programmed cell death-ligand 1, atezolizumab, chemotherapy, small cell lung cancer

des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Small cell lung cancer (SCLC) accounts for 14% of lung cancers, with only modest progress made in recent decades . [START_REF] Spigel | Rationale for chemotherapy, immunotherapy, and checkpoint blockade in SCLC: beyond traditional treatment approaches[END_REF] Chemotherapy remains the backbone of SCLC therapy. [START_REF] Rudin | Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline[END_REF] Despite the high SCLC chemosensitivity, survival is low (2 to 5 years) due to secondary chemoresistant relapses. Re-induction of platinum-etoposide or single-agent topotecan (or more recently, amrubicin, approved in Japan) are recommended for relapsed or refractory SCLC. In this second line setting, the survival of patients treated with either regimen is about 33 weeks. [START_REF] Eckardt | Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer[END_REF] Novel therapeutic approaches are under development to overcome secondary SCLC chemoresistance. Poly-(ADP-ribose) polymerase inhibitors, [START_REF] De Bono | Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers[END_REF] aurora A kinase inhibitors, [START_REF] Yan | Aurora-A kinase: a potent oncogene and target for cancer therapy[END_REF] enhancer of zeste homolog 2 inhibitors, [START_REF] Gardner | Chemosensitive Relapse in Small Cell Lung Cancer Proceedsthrough an EZH2-SLFN11 Axis[END_REF] antibody-drug conjugates targeting DLL3, [START_REF] Rudin | Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-inclass, open-label, Phase I study[END_REF] and immune check-point inhibitors (ICPIs) [START_REF] Zimmermann | Delineating the Role of PD-1/PD-L1 Blockade in Advanced SCLC[END_REF] are under evaluation in relapsed SCLC. Meanwhile, SCLC genome-sequencing is providing key insights into genomic alterations like ubiquitous loss of P53 and RB1 gene functions, common amplification of the cMYC proto-oncogene, and common inactivating mutations of the NOTCH gene family. [START_REF] George | Comprehensive genomic profiles of small cell lung cancer[END_REF] Most studies have highlighted a high tumor mutational burden (TMB) in SCLC.

Though the expression of programmed cell death-ligand 1 (PD-L1) by SCLC tumor cells is low, [START_REF] Yasuda | PD-L1 Expression in Small Cell Lung Cancer[END_REF] a strong rationale exists for introducing ICPIs that target the programmed cell death protein 1 (PD-1)/PD-L1 link on account of SCLC's high TMB. Several Phase 2 studies are currently investigating the efficacy and safety of pembrolizumab, [START_REF] Ott | Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study[END_REF] nivolumab, or nivolumab plus ipilimumab [START_REF] Antonia | Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, openlabel, phase 1/2 trial[END_REF] in patients with SCLC relapse after platinum-etoposide chemotherapy.

Several activity clues have emerged from these early development studies. Atezolizumab (MPDL3280A), an engineered PD-L1 antibody, has been approved in non-SCLC at a 1200mg dose based on most recent clinical data. [START_REF] Socinski | Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC[END_REF] IFCT 1603 was an open-label randomized non-comparative Phase 2 study that sought to evaluate atezolizumab's activity as systemic therapy in SCLC progressing after first-line platinum/etoposide-based chemotherapy.

Patients and Methods

Patients

Patients with histologically confirmed SCLC who experienced a relapse by failure of a first line chemotherapy consisting of platinum compound and etoposide were prospectively accrued. The main eligibility criteria were proven progressive disease other than brain metastasis or carcinomatous meningitis, performance status 0-2, measurable disease according to RECIST 1.1, and no active brain metastases. However, patients with brain metastases upon diagnosis were eligible if they achieved brain response during first-line therapy (including brain radiotherapy), maintaining their brain tumor response for 2 months prior to randomization. Other eligibility criteria were age ≥18 years; weight loss <10% over previous 3 months; baseline neutrophils ≥2500/mm 3 ; platelets ≥100 000/mm 3 ; bilirubin, alkaline phosphatase and transaminase levels <1.5 times normal upper limits; sodium >125mmol/L; normal calcium; creatinine clearance 40mL/min; normal electrocardiogram, and signed informed consent. Patients were ineligible if they had received corticosteroids at a daily dose >10mg (prednisolone or equivalent) for more than 10 days during the previous month, or had had prior autoimmune disease, unstable coronary angina or uncontrolled heart disease, prior human immunodeficiency virus infection, or chronic hepatitis B or C. The study was approved by an institutional review board (Sud -Mediterranée IV (Montpellier University, France) and was registered on clinicaltrials.gov under trial number NCT03059667. For all patients, the evaluation before randomization included a physical examination; standard chest X-ray; computed tomography (CT) of the upper abdomen; brain magnetic resonance imaging or CT; skeleton CT or positron emission tomography; quality-of-life assessment using the lung cancer symptom scale (LCSS); hematology (cell blood counts including hemoglobin and platelet counts); renal function (creatinine clearance); liver function (aspartate transaminase, alanine aminotransferase, bilirubin, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase, prothrombin time, and albumin); and assessment of calcium, phosphorus, and sodium levels.

Randomization and Masking

For minimization purposes, patients were stratified by performance status (0-1 versus 2), limited versus extensive disease according to Veterans Administration Lung Study Group classification [START_REF] Zelen | Keynote address on biostatistics and data retrieval[END_REF] at randomization, gender, and presumed disease sensitivity (refractory versus sensitive disease, the latter defined as relapse more than 90 days after ending first-line therapy). They were randomized (2:1) to either a) atezolizumab every 3 weeks until progression or unacceptable toxicity or b) conventional chemotherapy up to six cycles, delivered every three weeks.

Procedure

Anti-PD-L1 atezolizumab was administered at a fixed dose of 1200mg intravenously (IV). No dose reduction was allowed. Patients who experienced toxicity considered to be study drugrelated related and required a dose to be withheld, were temporarily suspended from study treatment. If atezolizumab was withheld because of adverse events for 42 days beyond the date when the next dose was due to be administered, then atezolizumab was discontinued, with the patient followed-up for safety and efficacy.

Conventional chemotherapy consisted of either re-induction of carboplatin-etoposide doublet or second-line oral or IV topotecan, the choice being at the investigator's discretion. The following protocol recommendations were made: 1) Carboplatin-etoposide was recommended for patients if they were deemed fit and had been relapse-free for at least 90 days after first-line therapy; 2) Topotecan was recommended for patients who did not meet criterion 1 and was to be administered according to an approved regimen of 2.3mg/m 2 orally or 1.5mg/m 2 IV on Days 1 to 5.

Third-line treatment was chosen based on each center's policy. Atezolizumab was not permitted for patients randomly assigned to chemotherapy who experienced secondary progression.

We assessed tumors on imaging at baseline, every 6 weeks for 24 weeks postrandomization, and every 9 weeks thereafter. Tumor response was assessed according to RECIST 1.1 on chest and upper abdomen CT and any other abnormal tests that have shown target lesions at screening and in case of suspicious signs. Tumor assessments continued until progression, irrespective of treatment discontinuation, and were centrally reviewed by reviewers blinded to randomization. Immune-modified RECIST criteria were not employed, and LCSS was recorded at each evaluation. PD-L1 expression was centrally assessed in archival or fresh tumor samples according to previously published scoring criteria [START_REF] Fehrenbacher | Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial[END_REF] using the VENTANA SP142 PD-L1 immunohistochemistry assay (Ventana Medical Systems, Inc., Tucson, AZ, USA). As described, tumor cell PD-L1 expression was scored as a percentage of total tumor cells, and tumor-infiltrating immune cells expressing PD-L1 was scored as a percentage of tumor area.

Briefly, TC0 was defined as PD-L1 expression by less than 1% of tumor cells, TC1 as PD-L1 expression by 1% to less than 5%, TC2 as PD-L1 expression by 5% to less than 50%, and TC3 as PD-L1 expression by 50% or more. Likewise, IC0 was defined as PD-L1 expression in less than 1% of tumor-infiltrating immune cells, IC1 as PD-L1 expression in 1% to less than 5%, IC2 as PD-L1 expression in 5% to less than 10%, and IC3 as PD-L1 expression in 10% or more. A composite score was arrived at by summing the IC and TC scores. PD-L1 expression was not used as a stratification criterion. rejected if at least 12/45 patients were responders. Consequently, the planned accrual was 45 patients in two stages.

The between-group distribution of qualitative variables was compared using the ² test or Fisher's exact test. For each patient, dose intensity was calculated taking into account the actual cycle number. Probability of survival was estimated by Kaplan-Meier method, with survival differences analyzed using log-rank tests. Hazard ratios and 95%CIs were estimated using a Cox model adjusted for stratification factors The variables to be tested in the model were selected based on univariate analysis results (P <0.20). A P level <0.05 was considered statistically significant. SAS software (Version 9.3) was used.

Results

Patients

From March to December 2017, 73 patients were accrued by 24 French institutions (Fig. 1).

Forty nine patients were randomly allocated to the atezolizumab group and 24, to the chemotherapy group. Six atezolizumab patients were ineligible due to brain metastases (n=3) or corticosteroid use >10mg over the previous month (n=3). Demographic characteristics were well-balanced between both groups (Table 1): 83.7% of atezolizumab patients had a performance status of 0-1, 79.6% extensive disease, and 67.3% sensitive relapse (progression 90 days after last first-line chemotherapy dose). The data cutoff took place on June 30, 2018.

Efficacy and Compliance

In the atezolizumab group, 1 of the 43 eligible patients achieved an objective response at Week 6, resulting in 2.3% objective response rate (95%CI: 0.0; 6.8) while 8 other patients had stable disease, resulting in disease control rate of 20.9% (95%CI: 8.8; 33; Table 2). Of the 20 eligible patients randomly allocated to chemotherapy, two achieved a tumor response at Week 6 (10%, 95%CI: 0.0; 23.1).

One atezolizumab patient did not receive any treatment owing to rapid overall clinical status deterioration. Among the 48 patients who received at least one atezolizumab dose, the median (range) number of cycles administered was 2 (1; 24). At cutoff, 45 of 49 patients had been withdrawn from the atezolizumab group, of whom 39 had developed disease progression (86.7%) and six died (13.3%). Three patients were pursuing the study treatment in the atezolizumab group and none in the chemotherapy group.

Survival

Median follow-up was 13.7 months (95%CI: 12.7; not reported). Median PFS in the intentionto-treat population significantly differed between both groups (1.4 months [1.2; 1.5] versus 4.3 months [1.5; 5.9] in atezolizumab and chemotherapy groups, respectively; adjusted hazard ratio (HR) atezolizumab arm = 2.26 [1.30; 3.93]; p=0.004; Fig. 2a). The 6-month PFS rate for atezolizumab was 6.3% (0.0%; 13.1%). Random allocation had no effect upon OS since date of randomization: median OS: 9.5 months; [3.2 ; 14.4] versus 8.7 months; [4.1 ; 12.7] for the atezolizumab and the chemotherapy group, respectively; adjusted HR atezolizumab arm = 0.84 [CI: 0.45 ; 1.58] ; p=0.60 (Fig. 2b). The 1-year OS rate for atezolizumab group was 42.5% (26.9%; 58.2%). Exploratory subgroup analyses of unstratified HRs were conducted according to gender, performance status (0-1 versus 2), disease sensitivity (refractory versus sensitive), and disease stage (limited versus extensive). We did not identify features of a favorable effect with atezolizumab (Fig. 2c).

After treatment discontinuation, 30 (65.2%) of the 46 patients in the atezolizumab group for whom post study follow-up is available, were known to have received third-line treatment, primarily chemotherapy (25 of the 30 patients [83.3%]), with almost equal prescription of topotecan and carboplatin-etoposide doublet. In comparison, 16 of the 24 patients (66.7%) in the chemotherapy group received third-line treatment (Appendix). No patient received ICPIs or targeted therapy (Supplemental Table 1).

Safety

In the 48 atezolizumab-allocated patients who received at least one infusion, immunemediated adverse events included hepatitis (two patients [4.2%], one Grade 1 and one Grade 2), colitis (two patients [4.2%], both Grade 1), arthralgia (three patients [6.3%], two Grade 1 and one Grade 2) and dysthyroidism (two patients [4.2%], one grade 1 hyperthyroidism, one hypothyroidisms, grade 1 and grade 2). Overall, musculoskeletal and connective tissue disorders of Grades 1-2 occurred in six patients (12.5%), while gastrointestinal disorders of Grades 1-2 occurred in nine (18.8%). We observed no pneumonitis. Table 3 lists specific toxicities and toxicities that occured in >10% of atezolizumab-treated patients. No adverse events led to atezolizumab discontinuation, with no atezolizumab-related deaths.

Quality of Life

We analyzed the proportion of patients who reported a decrease by at least one point in each symptom recorded by the LCSS. Most scores had improved at evaluation. Random allocation had no effect on the magnitude of improvement, with no statistical differences in the patient percentages with decreased scores between atezolizumab and chemotherapy (Fig. 3).

Markers

Archived tumor tissue specimens were available from 59/73 patients (80.8%). Of these, five contained <10% tumor cells and were not suitable for immunohistochemistry. Only one (1.8%) of the remaining 54 specimens available was proven positive for PD-L1 and was scored TC2, whereas the other 53 tissue samples were scored TC0. This low PD-L1 expression precluded any subgroup analyses by tumor cell score. Tumor-infiltrating immune cell scores were available for 54 specimens. Of these, 16 were positive, of which 10 were scored IC1, 5 were scored IC2 (one of these was the specimen above scored TC2), and 1 was scored IC3. Regardless of the allocated group, Kaplan Meier estimates of PFS and OS in whole patient population with available tumor specimen showed no statistical difference according to SP142 PD-L1 tumor-infiltrating immune cell score (Supplemental Fig. 1). OS estimates showed no statistical interaction between PD-L1 composite score positivity and treatment group (p=0.68). In the atezolizumab group, 25% of patients exhibiting IC0 score achieved disease control at Week 6, whereas all patients with a positive score experienced progressive disease (Supplemental Table 2).

Discussion

In this trial evaluating an engineered anti-PD-L1 antibody as second-line therapy for SCLC after failure of a first-line treatment by platinum and etoposide, 1200mg atezolizumab monotherapy given once every 3 weeks resulted in a 2.3% response rate and a 1.4-month median PFS, thus precluding initiation of the Phase 3 study part. We would like to briefly discuss three major aspects pertaining to our study: 1) literature update on PD-L1 blockade in second-line SCLC; 2) search for markers as efficacy predictors of anti-PD-L1 or anti-PD-1 antibodies in SCLC; 3) future direction of SCLC immunotherapy, including combined therapy with anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) plus anti-PD-L1 blockade and chemotherapy plus immunotherapy.

Nivolumab and pembrolizumab, two anti-PD-1 antibodies, have been tested in second-line SCLC therapy. [START_REF] Ott | Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study[END_REF][START_REF] Antonia | Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, openlabel, phase 1/2 trial[END_REF] The CheckMate 032 trial was conducted in patients with disease progression following platinum-containing regimens or subsequent second line treatment. [START_REF] Antonia | Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, openlabel, phase 1/2 trial[END_REF] Patients were not selected based on PD-L1 expression. They were allocated to four groups, one group receiving nivolumab at 3mg/kg once every 15 days, and the three other groups receiving different combinations of nivolumab and ipilimumab once every 3 weeks for four cycles followed by nivolumab at 3mg/kg once every 15 days. We discuss the combination groups below. Some 10% of 98 patients who received 3mg/kg nivolumab monotherapy achieved a response after a median 6.5-month follow-up. Median OS was 4.4 months (95%CI;3.0; 9.3) and median PFS 1.4 months (95%CI: 1.4; 1.9). Toxicity was mild-moderate under nivolumab monotherapy. The KEYNOTE 028 trial, which evaluated pembrolizumab efficacy in different tumor types, accrued 24 patients with PD-L1-positive SCLC (1% stained tumor cells) with disease progression after first-line treatment or beyond [START_REF] Ott | Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study[END_REF] Those 24 patients were selected from 163 patients screened for PD-L1 expression, with a rather low incidence of positive cases. The response rate was as high as 33%, but median PFS was 1.9 months and median OS 9.7 months.

Maintenance therapy is another approach for overcoming chemoresistant relapse. In a published Phase 2 single-group study, pembrolizumab was given as maintenance therapy after frontline platinum-based chemotherapy in metastatic SCLC patients. [START_REF] Gadgeel | Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC)[END_REF] Patients were not selected for PD-L1 tumor expression. Overall, 45 patients with response or stable disease after four to six cycles of platinum and etoposide chemotherapy received IV pembrolizumab at 200mg once every 3 weeks. Median PFS was 1.4 months, median OS 9.6 months, and 1year OS rate 37%. Thus, after first-line chemotherapy, anti-PD-1 and anti-PD-L1 antibodies as second-line treatment or maintenance therapy have yielded low disease control rates.

Median PFS has been proven remarkably similar across studies, being 1.4 months in the KEYNOTE 032 study, maintenance pembrolizumab study, and this atezolizumab study, and 1.9 months in the KEYNOTE 028 study. Although between-trial comparisons prove hazardous, these results are no better than those yielded by topotecan in second-line therapy. In a phase 3 study comparing oral with IV topotecan as second-line therapy, oral topotecan yielded an 18.3% response rate, median PFS of 2.8 months, and median OS of 7.7 months. [START_REF] Eckardt | Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer[END_REF] In our randomized Phase 2 study, patients allocated to chemotherapy achieved a median PFS of 4.3 months and median OS of 8.7 months. These results compared well with literature and thus validate the study population. Consequently, one can consider that PD-L1 blockade in second-line therapy for recurrent SCLC does not display a sufficient efficacy signal. These disappointing overall efficacy results notwithstanding, all the aforementioned studies, including ours, have shown that a small proportion of patients receiving PD-1/PD-L1 blockade achieved sustained disease control. For instance, in our study, 12% of patients received at least eight cycles of atezolizumab, with 1-year survival of 42.5%. The challenge is to identify these patients likely to benefit from PD-L1 blockade. In our study, exploratory subgroup analyses of unstratified HRs according to gender, disease sensitivity, performance status, and disease stage did not identify predictors of favorable atezolizumab effects. Other studies likewise failed to identify clinical features for pinpointing a subpopulation that may benefit from PD-1 blockade.

Two important biomarkers predictive of clinical benefit have been identified in non-SCLC patients receiving anti-PD-1 antibodies. These are the tissue expression of PD-L1 and TMB.

The PD-L1 expression incidence has been shown to vary in non-SCLC, owing to differing clinical and genotypic features of each population tested. Additionally, the immunohistochemistry method used and positivity threshold led to not entirely concordant findings. [START_REF] Hirsch | PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project[END_REF] Nevertheless, a rough evaluation of PD-L1 expression in non-SCLC yielded rates of between 30 and 40%. In SCLC, the expression has been tested in smaller populations, but the incidence of PD-L1 expression is probably much lower. In our study, we were able to analyze PD-L1 expression in tumors of 54 patients, with only one tumor PD-L1-positive (2%).

In the maintenance pembrolizumab study, 3/30 specimens were positive using the 22C3 antibody. [START_REF] Gadgeel | Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC)[END_REF] In the CheckMate 032 study, of 148 assessable tumor samples, 7 (5%) had 5% or greater PD-L1 expression. [START_REF] Antonia | Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, openlabel, phase 1/2 trial[END_REF] A study evaluating SCLC PD-L1 expression only found 1 positive specimen in 39 with a 22C3 test used at the  1% tumor cell level. [START_REF] Yasuda | PD-L1 Expression in Small Cell Lung Cancer[END_REF] Low expression levels preclude robust subgroup analyses of the relationship between PD-L1 tissue expression and patient outcome. The CheckMate 032 and maintenance pembrolizumab studies reported no survival difference between patient groups based on PD-L1 expression, although it may be said that the small number of patients in the positive PD-L1 subgroups made it difficult to draw any conclusions. [START_REF] Ott | Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study[END_REF][START_REF] Antonia | Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, openlabel, phase 1/2 trial[END_REF] Interestingly, a composite score incorporating infiltrating immune cells and tumor cells was used in the maintenance pembrolizumab study. [START_REF] Gadgeel | Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC)[END_REF] That exploratory analysis suggested that patients with high scores had better prognosis, but no statistical analysis could be conducted due to the small sample size. Because PD-L1 expression by SCLC tumor cells is infrequent whereas expression by infiltrating immune cells is more frequent, there is a case for evaluating the composite score as a predictive biomarker of sensitivity to anti-PD-L1 or PD-1 therapy. However, in our study, the infiltrating immune cell score did not show any relationship with treatment group.

TMB might be a more essential marker, particularly in SCLC, since most studies have reported a high number of complex genomic alterations. 9 Among them, loss of P53 and RB1 gene functions, amplification of cMYC proto-oncogene, frequent inactivating mutation of NOTCH gene family, and evidence of chromothripsis. On exome analysis, the median number of non-synonymous mutations was shown to range from 8 to 10 mutations per megabase pair. In the CheckMate 032 study, an exploratory analysis of the relationship between TMB and ICPI response revealed patients with high TMB to exhibit longer PFS and OS than those with low TMB. [START_REF] Antonia | Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, openlabel, phase 1/2 trial[END_REF] As PD-L1 blockade in SCLC appears insufficient to achieve tumor control in second-line therapy, other strategies could be explored. The first might be to combine CTLA-4 and PD-1 ICPIs. In the CheckMate 032 study, the median survival of patients allocated to the ipilimumab plus nivolumab combination was numerically higher than that observed with nivolumab alone, 12 being 7.7 months for nivolumab at 1mg/kg plus ipilimumab at 3mg/kg and 6.0 months for nivolumab at 3mg/kg plus ipilimumab at 1mg/kg. As for many other cancers, nivolumab plus ipilimumab can lead to lasting responses not seen with second-line chemotherapy for small cell cancer. Ipilimumab plus nivolumab activity also depended on the TMB and was independent of tumor cell PD-L1 expression. The combination caused a higher rate of specific immune-mediated adverse events, including two toxic deaths (one due to myasthenia gravis and the other to pneumonitis). The Stimuli trial (NCT02046733) is evaluating this combination as maintenance for patients successfully treated with concomitant chemoradiotherapy for limited SCLC. Tremelimumab plus durvalumab is another combined anti-CTLA-4 and anti-PD-L1 immunotherapy, which was tested in cohort A of the Baltic Phase 2 study. [START_REF] Bondarenko | Preliminary Efficacy of Durvalumab plus Tremelimumab in Platinum-refractory/resistant Extensive Disease-Small Cell Lung Cancer from Cohort A of the Phase 2 BALTIC Study[END_REF] In this study, 21 patients with platinum-refractory or resistant SCLC and good performance status were accrued. The response rate was 9.5% (95%CI: 1.2; 30.4) and median PFS was 1.9 months (95%CI;1.8; 4.3). Some 47% of patients experienced treatment-related adverse events, of which three were severe and one was fatal. The case for combined ICPIs in SCLC has yet to be borne out in Phase 3 trials.

Combined chemotherapy and immunotherapy is another avenue being explored to improve SCLC patient outcome. In a Phase 1/3 study evaluating atezolizumab plus carboplatinetoposide in the first line, 403 patients with extensive SCLC, good performance status, measurable disease and no prior systemic therapy were randomly assigned 1:1 to receive carboplatin-etoposide for four cycles with or without atezolizumab. [START_REF] Horn | First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer[END_REF] The immunotherapy was maintained until disease progression or unacceptable toxicity. PFS and OS improved in the investigational group, with a median OS of 12.3 versus 10.3 months for atezolizumab plus carboplatin-etoposide and carboplatin-etoposide alone, respectively (HR: 0.70; p=0.0069). The 1-year OS was 51.7% versus 38.2%, respectively. In a subgroup analysis of OS, In this study, TMB tested using a blood-based assay, did not modify the favorable effect of atezolizumab. This result may be considered a step forward after three decades of unchanged standard therapy for extensive SCLC. Similarly, durvalumab ± tremelimumab in combination with platinum-based chemotherapy in untreated extensive SCLC is being tested in a phase 3 study (clinicaltrials.gov identifier: NCT03043872).

Whether chemo-naive patients is a more favorable setting for IPCI efficacy than refractory SCLC, is unknown, but, the synergistic effect of IPCI plus chemotherapy as already suggest in other malignancies might have contributed to the final results of IMpower 133. One could speculate that the unfavorable PFS observed was due to rapid disease progression in patients in whom atezolizumab was inactive. Whether or not chemotherapy plus atezolizumab could overcome this phenomenon remains to be established. Interestingly, several patients in our study had sustained disease control. PD-L1 expression on tumor cells or tumor-infiltrating immune cells did not differ in this subgroup. Next-generation sequencing on tissue-and cell-free DNA extractions is ongoing using base-position error rate analysis.

An attempt at identifying gene alterations predictive of atezolizumab-induced disease control is in progress and will be submitted separately.

The main limitation of our study might belong to the choice of ORR as the primary endpoint.

It has been reported that there is a frequent lack of consistency between ORR and OS in IPCI trials. Nevertheless, in the setting of early evaluation of atezolizumab in recurrent SCLC we have considered ORR at 6 weeks as a reasonable endpoint for a phase 2, taking into account the lack of knowledge of ICPI activity in this setting at time when we designed this study. ORR was chosen in an attempt to detect a signal, as early as possible in the course of the study in order to avoid continuation of an inactive treatment in patients who experienced early progression.

In conclusion, the IFCT-1603 trial failed to demonstrate a significant efficacy signal for singleagent atezolizumab as treatment for relapsed SCLC, with no unexpected safety signal observed. Some patients receiving atezolizumab exhibited sustained disease control. PD-L1 expression did not differ in this subgroup. A genotype analysis of available tumor specimens from these patients is in progress.

Figure 1 .

 1 Figure 1. CONSORT diagram of the phase 2 clinical trial to evaluate atezolizumab as

Figure 2 .

 2 Figure 2. Survival analysis of the phase 2 clinical trial to evaluate atezolizumab as second-

Figure 3 .Supplemental Figure 1 .

 31 Figure 3. Percentage of patients with lower Lung Cancer Symptom Scale score at Week 6

Table 1 .

 1 Comparison of Demographic and Disease Characteristics at Time of Randomization for Small Cell Lung Cancer Patients in Second-Line Therapy Randomly Assigned to

	Tables
	Atezolizumab or Chemotherapy
			A -Chemotherapy	B -Atezolizumab	Total
	Descriptive Statistics	(N=24)	(N=49)	(N=73)	p-value
	Gender	Female	N '(%)	11 (45.8)	19 (38.8)	30 (41.1)	0.56
	Age (years)		Median	63.5	65.9	64.7	0.15
			Range	[51.8-81.0]	[51.1-85.5]	[51.1-85.5]
	Performance	0-1	N '(%)	21 (87.5)	41 (83.7)	62 (84.9)	1.00
	status
		2	N '(%)	3 (12.5)	8 (16.3)	11 (15.1)
	Stage at time of	Extensive N '(%)	15 (62.5)	39 (79.6)	54 (74.0)	0.12
	random allocation
	Relapse status*	Refractory	N '(%)	10 (41.7)	16 (32.7)	26 (35.6)	0.45
		disease
		Sensitive	N '(%)	14 (58.3)	33 (67.3)	47 (64.4)
		disease
	Smoker	Yes	N '(%)	23 (95.8)	47 (95.9)	70 (95.9)	1
	(current or former)
	* Sensitive disease defined as progression 90 days after last dose of first-line
	chemotherapy; otherwise, refractory.

Table 2 .

 2 RECIST Response Evaluation at Week 6 for Eligible Patients with Small Cell Lung Cancer in Second-Line Therapy Randomly Assigned to Atezolizumab or Chemotherapy

	Descriptive Statistics			Chemotherapy	Atezolizumab	Total
				(N=20)	(N=43)	(N=64)
	Objective response at 6	Objective	N (%)	2 (10)	1 (2.3)	3 (4.8)
	weeks	response
		Objective	95% CI [0.0; 23.1]	[0.0; 6.8]	[0.0; 9.9]
		response
	Disease control rate at 6	DCR	N (%)	13 (65)	9 (20.9)	22 (34.9)
	weeks
		DCR	95% CI [44.1; 85.9]	[8.8; 33.1]	[23.1; 46.7]
		Progression	N (%)	6 (30)	30 (69.8)	36 (57.1)
		Progression	95% CI [9.9; 50.1]	[56.0; 83.5]	[44.9; 69.4]
		Not Done/Not	N (%)	1 (5.0)	4 (9.3)	5 (7.9)
		Evaluable
		Not Done/Not	95% CI [0.0; 14.6]	[0.6; 18.0]	[1.3; 14.6]
		Evaluable

This work was supported by the Intergroupe Francophone de Cancérologie

Thoracique (IFCT: French Cooperative Thoracic Intergroup) and received an unrestricted grant from Roche SA France. Roche also supplied atezolizumab but played no role in trial design, data collection, data interpretation, discussion, or manuscript writing.

Outcomes

The primary endpoint was the objective response rate (ORR) as assessed by the investigator at Week 6 (with mandatory confirmation at week 12) in eligible patients randomly assigned to the atezolizumab group. Secondary endpoints included overall survival (OS, time from randomization to death) and progression-free survival (PFS, time from randomization to either RECIST 1.1 disease progression or death from any cause, whichever occurred first) in the intention-to-treat population of the experimental group. Further secondary endpoints were adverse events (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0); quality of life; response rate in the experimental group as assessed by panel; response rate according to tissue PD-L1 expression; response rate in control arm.. Particular attention was paid to specific immunological adverse events. The safety and compliance population comprised all randomized patients who received at least one dose, with the actual treatment received being taken into account if this differed from the treatment to which the patient had been randomized.

Statistical Analysis

Only the experimental group was assessed for efficacy, with conventional chemotherapy group used as a comparator with literature data. This was an attempt to validate the study population while preventing any selection bias. The maximum sample size was calculated based on α, β, and the expected effect size using a test for single binomial proportion for a two-stage design with 2:1 randomization and O'Brien-Fleming stopping rules, allowing for early stopping after stage I. The software East 6.0 was used. A response rate of P0= 0.15 or less was considered unacceptable. However, we considered the response rate good if Pa= 0.33. The computation was based on the following assumptions: P0=0.15; Pa=0.33; statistical power of 0.90; and a one-sided significance level of 0.05. The null hypothesis was


Athanase Millogo
email: athanase.millogo@gmail.com.

A Helena Ngowi

Hélène Carabin

Rasmané Ganaba

Alida Da

Pierre-Marie Preux

Knowledge, attitudes and practices related to epilepsy in rural Burkina Faso

Keywords: Attitudes, Beliefs, Burkina Faso, Epilepsy, Knowledge, Qualitative research

Objectives: To assess knowledge, beliefs, attitudes and practices regarding epilepsy and neurocysticercosis in rural areas in Burkina Faso. Materials: The interviews were designed to assess general perception of epilepsy, cultural beliefs and practices regarding epilepsy and people with epilepsy (PWE), and knowledge about the link between human epilepsy and porcine cysticercosis. This qualitative study used in-depth interviews with different categories of community members, including PWE, healthcare providers (HCPs) and traditional healers in three villages in rural Burkina Faso. Results: All respondents showed a good knowledge of epilepsy symptoms but very little knowledge on causes of the disease. In this community, epilepsy was often associated with witchcraft (commonly termed "black magic"). People with epilepsy were marginalized and denied certain rights such as school education and marriage. They also relied mainly on traditional medicine with a prominent role played by traditional healers. While medical personnel knew that controlling seizures would depend on the cause, the traditional healers reported to be able to cure all kinds of epilepsy as long as the patient adhered to taboos. The main "treatments" prescribed by traditional healers were to stay away from fire and refrain from pork consumption. Pork fat was believed to reduce the effectiveness of the traditional medicine. Conclusion: For effective monitoring and management of epilepsy in Burkina Faso, there is a need to promote better knowledge of the disease in the community, including HCPs, and traditional healers.

Background

Epilepsy is a chronic non-communicable disorder of the brain that affects people of all ages.

More than 80% of epilepsy cases worldwide live in developing countries [START_REF] Boer | The global burden and stigma of epilepsy[END_REF][START_REF] Ba-Diop | Epidemiology, causes, and treatment of epilepsy in sub-Saharan Africa[END_REF]. The perception of the condition varies according to regions and cultures. In many developing countries, the fear of discrimination and stigma makes people with epilepsy (PWE) hide their condition or feel that it brings shame to themselves or their relatives [START_REF] Atadzanov | Epilepsy-associated stigma in Zambia: what factors predict greater felt stigma in a high stigmatized population?[END_REF][START_REF] Baskind | Epilepsy-associated stigma in sub-Saharan Africa: the social landscape of a disease[END_REF][START_REF] Birbeck | The status of people with epilepsy in rural sub-Saharan Africa[END_REF][START_REF] Rafael | Sociocultural and psychological features of perceived stigma reported by people with epilepsy in Benin[END_REF]. This fear may also lead to PWE seeking treatment from traditional healers instead of seeking care from modern health services [START_REF] Kumari | Stigma and quality of life in individuals with epilepsy: A preliminary report[END_REF]. Many studies worldwide have shown that PWE are forbidden to marry or attend schools [START_REF] Cuong | Survey of public awareness, attitudes, and understanding towards epilepsy in Nhan Chinh, Hanoi, Vietnam[END_REF][START_REF] Barennes | Epilepsy in Lao PDR: From research to treatment intervention[END_REF][START_REF] Hasan | Understanding of and attitudes toward epilepsy among the urban Chinese population in Malaysia[END_REF][START_REF] Ndoye | Prevalence of epilepsy, its treatment gap and knowledge, attitudes and practice of its population in sub-urban Senegal: an ILAE/IBE/WHO study[END_REF][START_REF] Nuhu | Social consequences of epilepsy: a study of 231 Nigerian patients[END_REF][START_REF] Tran | Epilepsy in Laos: knowledge, attitudes, and practices in the community[END_REF]. In many Sub-Saharan African countries, traditional beliefs lead most PWE to opt for traditional treatment, resulting in inadequate management of the disease [START_REF] Ndoye | Prevalence of epilepsy, its treatment gap and knowledge, attitudes and practice of its population in sub-urban Senegal: an ILAE/IBE/WHO study[END_REF][START_REF] Matuja | Knowledge Attitude and Practice towards epilepsy in secondary school students in Tanzania[END_REF][START_REF] Njamnshi Ak | General public awareness, perceptions, and attitudes with respect to epilepsy in the Akwaya Health District, South-West Region, Cameroon[END_REF][START_REF] Njamnshi | A survey of public knowledge, attitudes, and practices with respect to epilepsy in Badissa Village, Centre Region of Cameroon[END_REF][START_REF] Njamnshi | Public awareness, perceptions, and attitudes with respect to epilepsy in Ebolowa and Sangmelima -Urban Cameroon[END_REF][START_REF] Njamnshi | A community survey of knowledge, perceptions, and practice with respect to epilepsy among traditional healers in the Batibo Health District, Cameroon[END_REF][START_REF] Nyame | Epilepsy: knowledge, attitude and practice in literate urban population, Accra, Ghana[END_REF]. As the majority of PWE do not seek health care services, the magnitude of epilepsy cannot be accurately estimated through medical data. The insufficiency of expertise in neurology also leads physicians at the primary care and hospital levels to neglect epilepsy [20]. In Burkina Faso only seven neurologists, who practice in the two major urban areas of the country, serve the population of 13.6 million people. This obvious resource-gap leads to an important under-estimation of the burden of epilepsy in the country.

Epilepsy can be caused by various factors, including congenital, infectious and physical factors (such as head injuries). Neurocysticercosis (NCC) has recently emerged as an important infectious cause of epileptic seizures in areas where Taenia solium is endemic. A meta-analysis reported the frequency of NCC in PWE to be consistent across endemic countries, accounting for approximately 29.0% (95%CI: 22.9%-35.5%) of PWE [START_REF] Ndimubanzi | A systematic review of the frequency of neurocysticercosis with a focus on people with epilepsy[END_REF].

Knowledge on this infectious cause of epilepsy would enable implementation of appropriate interventions for this treatable and preventable cause of epilepsy.

Studies conducted around the world suggest that perceptions and attitudes towards epilepsy vary according to different cultural settings [8, 11, 13, 15-17, 19, 21, 22]. In Burkina Faso, each of the 60 ethnic groups has specific beliefs towards epilepsy and uses a different name for the disease. The few studies ever conducted on knowledge, attitudes and perceptions towards epilepsy were done in urban areas in the western part of the country [START_REF] Millogo | Aspects socioculturels de l'épilepsie en milieu scolaire à Bobo-Dioulasso (Burkina Faso)[END_REF][24][START_REF] Millogo | Knowledge of epilepsy and attitudes towards the condition among schoolteachers in Bobo-Dioulasso (Burkina Faso)[END_REF][START_REF] Millogo | Epilepsy and traditional medicine in Bobo-Dioulasso (Burkina Faso)[END_REF], and no study had assessed these aspects of epilepsy in rural areas. A better understanding of knowledge, attitudes and perceptions of epilepsy would guide the development of appropriate educational programmes on epilepsy in addition to guiding the healthcare providers to better manage the disease. Understanding knowledge, perceptions, attitudes and behaviours of various care givers regarding epilepsy provides a unique feature of this study as most previous studies gathered such information primarily from PWE and the general population. The main objective of this study was to assess knowledge, beliefs, attitudes and practices of PWE, community members, traditional healers and health care providers (HCPs) regarding epilepsy and NCC in rural areas in Burkina Faso.

Methods

Study sites

This qualitative exploratory study was part of a pilot study conducted in 2007 to assess the presence of cysticercosis and its association with epilepsy in three villages of Burkina Faso (Figure 1). Details about the main study can be found elsewhere [START_REF] Carabin | Evaluation du Fardeau Economique de la Cysticercose au Burkina Faso (EFECAB). Seroprevalence to the antigens of Taenia solium cysticercosis among residents of three villages in Burkina Faso: A cross-sectional study[END_REF][START_REF] Ganaba | Factors associated with the prevalence of circulating antigens to porcine cysticercosis in three villages of Burkina Faso[END_REF][START_REF] Nitiema | Prevalence case-control study of epilepsy in three Burkina Faso villages[END_REF][START_REF] Millogo | Prevalence of neurocysticercosis among people with epilepsy in rural areas of Burkina Faso[END_REF].

Study population and sampling procedure

The inclusion criteria for study participants were: being over the age of 16 and agreeing to participate in the interviews, irrespective of gender or religion. In each study village, participants were classified into five categories based on their age, professions and epilepsy statuses. The following participant groups were used: young adults (≥16-40 years), older adults (≥40 years), traditional healers, health care providers (HCPs), and PWE. There was no traditional healer in Nyonyogo. Inclusion of these different groups aimed at obtaining information from people with different roles in the community. To obtain the required categories of respondents, purposive sampling was adopted as it was the most appropriate approach. Local leaders guided the research team in this procedure after the leaders were informed about the objectives of the study.

Study design and data collection procedure

This was a qualitative exploratory study. A semi-structured interview guide created by the first author (Athanase Millogo) was used to conduct one-on-one in-depth interviews with each study participant. The interview guide consisted of five major topics which were used to initiate the discussions and probing was used to explore the issues further. The interviews were designed to assess general perception of epilepsy, cultural beliefs and practices towards epilepsy and PWE, and knowledge about the link between human epilepsy and porcine cysticercosis. All interviews were conducted by one of the co-authors (Alida Da). The guide was pilot tested in a different village before its use. All interviews were recorded using a voice recorder. The interviews were tape-recorded in local languages (Moore or Lyele) depending on the setting and lasted from 20 to 40 minutes.

Data analysis

The tape-recorded interview scripts were transcribed in Microsoft Word and translated from the local languages into French and English and back translated in Moore or Lyele to insure the accuracy of the translations. The translations were made by interpreter using Moore or Lyele as native language and able to translate from French to Moore or Lyele. Data were analyzed by three independent analysts (Alida Da, Athanase Millogo, Helena A. Ngowi) using N-VIVO version 1.1, note based analysis and MAXQDA, respectively. The reason for having three independent analysts was for triangulation to verify the conclusions reached. Data were coded by assigning same codes in passages or quotations with similar concepts. The codes were then quantified to identify thematic ideas for each aspect investigated. A theme was identified if an idea was mentioned by at least 60% of respondents. The first stage of analysis involved all respondents regardless of the village to identify the main emerging and recurring themes related to the research questions [START_REF]Qualitative data analysis[END_REF]. The themes were not predetermined. Rather they emerged from the data under each topic of discussion based on content analysis. Agreement between the different analysts was over 87% in all topics investigated. Having analyzed the responses generally across the groups, the analysts compared the responses to similar questions between the different categories of respondents (normal villagers, PWE, HCPs and traditional healers) by analyzing each case independently.

Ethics

The study protocol was reviewed and approved by the ethical committee of the Centre MURAZ (Ref. 02-2006/CE-CM) and by the Institutional Review Board of the University of Oklahoma Health Sciences Center (IRB# 12694). Each participant was asked to read or, if not able to read, was read an informed consent. The interviewer (A. D.) answered any question that that the potential participant may have about the study. Individuals willing to participate signed the consent form or oral consent was obtained and documented by A. D. on the consent form for those who could not read. Participants' unique identifications were kept confidential and each participant had the right to stop the interview at any time.

Results

Twenty-nine people were asked and agreed to participate in the study (21 males, 8 females), including young adults (n = 10), older adults (n = 9), PWE (n = 6), HCPS (n = 2 who were present at the time of the study) and traditional healers (n = 2). Ten of the respondents were residing in Batondo, 10 in Pabré and nine in Nyonyongo. Most respondents (n = 23) had no formal education, six had elementary or primary school education and one HCP had a high school education. A total of 7 main themes emerged and were related to the perception of disease and health, perceived causes of epilepsy, clinical symptoms of epilepsy, social behavior towards PWE, link between epilepsy and pork consumption, risk for person to become epileptic, knowledge about treatment and therapeutic itineraries. The mean age of respondents was 41.2 years.

Knowledge about epilepsy and its perceived causes

Recognition of epilepsy and names referring to the condition

All respondents had a good knowledge of epilepsy symptoms. "During the seizure, the subject shouts, stays motionless for a while, dribbles, loses consciousness" and "he (PWE) may fall down and lose urine involuntarily". This description is related to tonic-clonic seizures which are generally well recognized in the community. Epilepsy was referred to as "councounbolo" (i.e disease that starts suddenly) or "kimina mayolo" (i.e bad disease) in Batondo. In Pabré and Nyonyogo, epilepsy was locally called "bamsobdoum'' (i.e disease that makes you faint) or ''kissinkiri'' (i.e epilepsy).

Knowledge of the causes of epilepsy

There was little knowledge about the causes of epilepsy among all groups except the HCPs.

The theme idea that emerged during the interviews was that epilepsy was caused by witchcraft (spells) or satanic (evil spirits) causes. A HCP from Batondo stated "Most of the time, this disease (epilepsy) is associated with evil spirits. That is why the persons with epilepsy begin treatment with traditional methods". A PWE from Nyonyogo said: "I got this disease from evil spirits". Another PWE from Pabré said: "It is a disease some spirits passed on me. One day, as I was riding my bicycle, I felt an invisible force dragging the bicycle, and eventually I fell off". Congenital causes have also been mentioned by a young man from Batondo: "A person can be born with it". Other causes were also mentioned such as contact with saliva or the left hand of PWE during seizures. A few individuals mentioned other causes such as pork consumption. In this case, epilepsy was mainly associated with pork fat.

In summary, the participants identified two broad categories for the causes of epilepsy namely mystical, which was by far the most common, and genetic causes. No respondent mentioned a link between undercooked pork consumption, poor sanitation and epilepsy.

Attitudes and perceptions of PWE regarding epilepsy

The theme idea that resulted from this topic was that PWE choose traditional rather than modern medicine for treatment. In addition, all PWE interviewed were willing to receive some type of treatment. However, the interviews with PWE suggested that they would resort to modern medicine only if complications such as burns or other injuries associated with seizures were to occur or if traditional medicine fails. Priority to traditional over modern medicine was due to a local perception that epilepsy was specifically an African disease, and hence a belief that "White people" which meant modern medicine, had no medicine to cure it. A traditional healer from Pabré said: "Most of the time, the disease is linked to evil spirits… When they go to the dispensary, they don't recover because it is an African disease". Other unique causes were mentioned, such as a respondent from the older adults stating "It is a disease passed on to human beings by cats through food. When a cat's mouth gets in contact with food or when the animal licks a container later used unwashed, it leaves epilepsy germs."

Responses indicated a frequent switch to modern medicine with satisfactory results. Here is the point of view of one PWE from Batondo: "First I began with traditional treatments. My family did not want me to follow modern treatment. They thought that modern medicine cannot cure it... It is only last year that I began to go to the dispensary". One important prescription for patients under traditional medicine was to refrain from pork consumption.

The fat in the pork was said to inhibit the action of traditional medicines. Some PWE asserted having consulted traditional healers, this move being the first contact taken in their health seeking behaviour. According to traditional healers, epilepsy could be cured if one followed the treatment regimens and prescriptions whereas the HCPs believed that contrary to epilepsy from other causes, the inherited form was difficult to cure.

Respondents seemed sceptical about the effectiveness of modern treatment of epilepsy since they mentioned monitoring its effect on the seizures very closely. Even the medical nurse in Nyonyogo did not seem to be quite confident in the effectiveness of modern treatment for epilepsy: "There are treatments but you rarely see anybody who has been cured." This point is of great interest as HCPs are supposed to provide appropriate information to their community.

One PWE in Pabré village said: "I had a traditional treatment when my children decided to take me to a doctor. I am currently undergoing a treatment by a doctor. It is nearly 10 months I have not had any seizure."

Individual and social attitude towards epilepsy

Epilepsy affects the social role and the productivity of PWE. It creates an emotional and socio-economic burden to the caretakers of the patient. This burden leads to marginalization of PWE and their families. When respondents were asked on their attitudes towards PWE, there were various ideas, but no specific theme was identified. However, all the ideas revolved around moral suffering and stigma affecting PWE. Having epilepsy was perceived to be a shame to the family, and hence, most PWE in the study community were rejected. A traditional healer from Pabré said: "As epilepsy is a shameful disease, the epileptic individual is marginalized. He cannot enjoy the same rights as healthy people".

When the respondents were asked how other people in their village behaved towards PWE, two themes emerged: marginalization and denial of some rights such as school education, jobs, social interaction, and certain foods. A young lady with epilepsy confessed "… I am not badly ill-treated but I feel that they have no respect for me… I am excluded from what happens in the family. I have even been forbidden from managing my income on the ground that I am unable to do it". PWE face various types of social problems as they are often denied the right to decide for themselves, because, as reported one respondent from the older adults: "They are not in full possession of their mental faculties". This can be illustrated by the words used by a woman with epilepsy from Batondo: "People do not actually like the person affected by epilepsy.

They do not like to interact with him or her… No consideration for me at all. When I try to take interest in something, they find that I am different from other people and should

therefore refrain from interfering…" Another PWE from Batondo said "I am not respected. I do not have the right to go to public places. I have been given a separate cup and plate. They do not want me to get married…"

Knowledge about the link between pork consumption and epilepsy

When respondents were asked whether there was any link between epilepsy and pork consumption, the theme was a lack of knowledge of the link, even indirect. A few respondents (including a HCP) mentioned that cysts in pork meat could be associated with epilepsy. Most other respondents associated human epilepsy with consumption of pork fat.

Nevertheless, there was an indication that part of the knowledge on the link between epilepsy and pork consumption was influenced by the interviewer. For example, one respondent from Batondo said: "If what you said about the link between epilepsy and pork is true, therefore all villagers here are at risk since it is only this meat that we eat here".

Possible link between pork and epilepsy was also mentioned by a young respondent from Pabré village: "They (butchers) said that white cysts in pork can transmit epilepsy when the meat is not properly cooked." The following assertion is from a PWE in Pabré: "… My doctor told me that there is a relationship between epilepsy and insufficiently cooked pork...". This awareness is interesting to note as it could be a starting point for sensitization to good practice in cooking meat and also good sanitation in this community.

Discussion

This is the first qualitative study about the perception and attitudes toward epilepsy conducted a rural setting in Burkina Faso. We found that the knowledge about the causes of epilepsy was generally poor, that the indirect link between pork consumption and epilepsy was generally unknown, and that beliefs and attitudes towards PWE lead to stigmatization.

In many African countries, community members generally demonstrate good knowledge about the symptoms of epilepsy, especially those associated with generalized tonic-clonic seizures as reported in many other countries in Africa [START_REF] Matuja | Knowledge Attitude and Practice towards epilepsy in secondary school students in Tanzania[END_REF][START_REF] Njamnshi Ak | General public awareness, perceptions, and attitudes with respect to epilepsy in the Akwaya Health District, South-West Region, Cameroon[END_REF][START_REF] Njamnshi | A survey of public knowledge, attitudes, and practices with respect to epilepsy in Badissa Village, Centre Region of Cameroon[END_REF][START_REF] Nyame | Epilepsy: knowledge, attitude and practice in literate urban population, Accra, Ghana[END_REF][START_REF] Andriantseheno | Aspects socioculturels de l'épilepsie chez le Malgache[END_REF][START_REF] Millogo | Aspects socioculturels de l'épilepsie en milieu scolaire à Bobo-Dioulasso (Burkina Faso)[END_REF]. The finding that satanic and witchcraft powers as themes for the causes of epilepsy are not unique to this study. Epilepsy has been associated with witchcraft or evils spirits in several other African countries in both urban and rural areas [START_REF] Baskind | Epilepsy-associated stigma in sub-Saharan Africa: the social landscape of a disease[END_REF][START_REF] Ndoye | Prevalence of epilepsy, its treatment gap and knowledge, attitudes and practice of its population in sub-urban Senegal: an ILAE/IBE/WHO study[END_REF][START_REF] Matuja | Knowledge Attitude and Practice towards epilepsy in secondary school students in Tanzania[END_REF][START_REF] Njamnshi | A survey of public knowledge, attitudes, and practices with respect to epilepsy in Badissa Village, Centre Region of Cameroon[END_REF][START_REF] Njamnshi | A community survey of knowledge, perceptions, and practice with respect to epilepsy among traditional healers in the Batibo Health District, Cameroon[END_REF][START_REF] Nyame | Epilepsy: knowledge, attitude and practice in literate urban population, Accra, Ghana[END_REF], and in urban areas of Burkina Faso [START_REF] Millogo | Knowledge of epilepsy and attitudes towards the condition among schoolteachers in Bobo-Dioulasso (Burkina Faso)[END_REF][START_REF] Millogo | Epilepsy and traditional medicine in Bobo-Dioulasso (Burkina Faso)[END_REF]. Although this was not identified as a theme, some participants did mention transmission from person-to-person through saliva or physical contact as a possible cause of epilepsy, like others have found in several other countries [START_REF] Tran | Epilepsy in Laos: knowledge, attitudes, and practices in the community[END_REF][START_REF] Matuja | Knowledge Attitude and Practice towards epilepsy in secondary school students in Tanzania[END_REF][START_REF] Nyame | Epilepsy: knowledge, attitude and practice in literate urban population, Accra, Ghana[END_REF][START_REF] Arborio | Dimension socioculturelle de l'épilepsie (kirikirimasien) en milieu rural bambara (Mali)[END_REF].

One nurse was unsure of the effectiveness of modern treatment for epilepsy. The nurses' response is an important cultural issue. This may be related with this nurse's own cultural perception of epilepsy. The position of this nurse as a HCP and as a credible source of health information for community members is important to consider. HCPs in rural areas may have their own beliefs which could affect their practice, and in this case, discourage PWE from seeking modern treatment. This one statement calls for a larger scale study assessing knowledge of HCPs regarding epilepsy and its treatment in rural Burkina Faso. If the skepticism towards modern medicine is confirmed in this group, a revision of the training curricula for HCPs in Burkina Faso, taking into account cultural values, would be warranted.

Consistent with the beliefs regarding the causes of epilepsy being largely mystical, choosing a traditional treatment over a modern one was identified as a theme among the PWE interviewed. This is in agreement with many studies reporting that traditional medicine is believed to being able to cure epilepsy [START_REF] Matuja | Knowledge Attitude and Practice towards epilepsy in secondary school students in Tanzania[END_REF][START_REF] Njamnshi Ak | General public awareness, perceptions, and attitudes with respect to epilepsy in the Akwaya Health District, South-West Region, Cameroon[END_REF][START_REF] Nyame | Epilepsy: knowledge, attitude and practice in literate urban population, Accra, Ghana[END_REF][START_REF] Millogo | Knowledge of epilepsy and attitudes towards the condition among schoolteachers in Bobo-Dioulasso (Burkina Faso)[END_REF][START_REF] Millogo | Epilepsy and traditional medicine in Bobo-Dioulasso (Burkina Faso)[END_REF]. This may also be associated with the belief that the disease only affects African people and hence can only be treated by African medicine. Therefore, the choice of the type of treatment by the patient or his/her family is prompted by their beliefs and opinions about epilepsy in their cultural environment.

In many Sub-Sahara African countries, first-line treatment for epilepsy is provided by traditional healers [24,[START_REF] Birbeck | Seizures in rural Zambia[END_REF][START_REF] Preux | Antiepileptic therapies in the Mifi Province in Cameroon[END_REF]. However, fees for treatment of traditional healers might not be cheap [START_REF] Millogo | Epilepsy and traditional medicine in Bobo-Dioulasso (Burkina Faso)[END_REF][START_REF] Mushi | Social-cultural aspects of epilepsy in Kilimanjaro Region, Tanzania: Knowledge and experience among patients and carers[END_REF]. In Burkina Faso, generic forms of phenobarbital are available for less than 1US$ for a month's treatment, which should be affordable even for the rural and poor communities. Nevertheless, in this study as in many other studies in Sub-Saharan Africa [START_REF] Tran | Epilepsy in Laos: knowledge, attitudes, and practices in the community[END_REF][START_REF] Njamnshi Ak | General public awareness, perceptions, and attitudes with respect to epilepsy in the Akwaya Health District, South-West Region, Cameroon[END_REF][START_REF] Njamnshi | A survey of public knowledge, attitudes, and practices with respect to epilepsy in Badissa Village, Centre Region of Cameroon[END_REF][START_REF] Njamnshi | Public awareness, perceptions, and attitudes with respect to epilepsy in Ebolowa and Sangmelima -Urban Cameroon[END_REF][START_REF] Nyame | Epilepsy: knowledge, attitude and practice in literate urban population, Accra, Ghana[END_REF], it was observed that modern treatment was not the first choice for PWE. As the first contact of PWE in many areas in Africa, and also because they are more available than the modern HCPs, traditional healers should be included in any screening study and educational programmes about epilepsy in these settings. Because of the role they play in providing care in their community, traditional healers are often know who suffers from epilepsy in their community. They could contribute to building a bridge between traditional and modern medicines in order to reduce the treatment gap of epilepsy in Africa.

In some studies, misconceptions about epilepsy lead to stigma [START_REF] Barennes | Epilepsy in Lao PDR: From research to treatment intervention[END_REF][START_REF] Hasan | Understanding of and attitudes toward epilepsy among the urban Chinese population in Malaysia[END_REF][START_REF] Tran | Epilepsy in Laos: knowledge, attitudes, and practices in the community[END_REF] and stigma discourage PWE to seek modern healthcare. In our study, we found that the stigma resulting from epilepsy largely impacts the patients' social role and productivity. This has been reported in Zambia where women with epilepsy were more likely to deliver their babies at home rather than in a hospital [START_REF] Birbeck | The social and economic impact of epilepsy in Zambia: a cross-sectional study[END_REF]. The two themes identified regarding the general attitudes of villagers towards PWE, namely marginalization and denial of some rights, are in agreement with studies that have reported. PWE are forbidden from gardening, attending meetings, sharing meals with other members of their community and attending to public places [START_REF] Nuhu | Social consequences of epilepsy: a study of 231 Nigerian patients[END_REF][START_REF] Njamnshi Ak | General public awareness, perceptions, and attitudes with respect to epilepsy in the Akwaya Health District, South-West Region, Cameroon[END_REF][START_REF] Mushi | Social-cultural aspects of epilepsy in Kilimanjaro Region, Tanzania: Knowledge and experience among patients and carers[END_REF]. Studies conducted in Zambia have demonstrated that even when PWE are self-reliant, their daily life does not always improve [START_REF] Birbeck | The status of people with epilepsy in rural sub-Saharan Africa[END_REF]. In other studies, PWE have been shown to deny their epilepsy status to avoid stigmatization [START_REF] Nuhu | Social consequences of epilepsy: a study of 231 Nigerian patients[END_REF][START_REF] Mushi | Social-cultural aspects of epilepsy in Kilimanjaro Region, Tanzania: Knowledge and experience among patients and carers[END_REF][START_REF] Birbeck | The social and economic impact of epilepsy in Zambia: a cross-sectional study[END_REF]. It has also been shown that children with epilepsy in urban areas of Burkina Faso are excluded from schools [START_REF] Millogo | Knowledge of epilepsy and attitudes towards the condition among schoolteachers in Bobo-Dioulasso (Burkina Faso)[END_REF] and PWE in Zambia cannot marry or be employed [START_REF] Birbeck | The social and economic impact of epilepsy in Zambia: a cross-sectional study[END_REF], a fact which was reported in our study. Cultural differences in stigma associated with epilepsy may determine whether an individual seeks care for epilepsy. To better assess the perceptions and attitudes regarding epilepsy in these rural areas in Burkina Faso, quantitative studies to identify associated factors of the reported attitudes and practices in the community are needed.

Prior to any intervention to improve the management of epilepsy cases, there is a critical need to get the community commitment, help PWE and the surrounding communities to have a better knowledge of the disease and improve their health seeking behaviour.

Community programs to achieve these aims should be based on the local perceptions of epilepsy and needs and one must also consider social and cultural conditions in the region 37].

Conclusion

In order to promote community educational program regarding epilepsy in Burkina Faso, there is a need to take different socio-cultural aspects into consideration, develop collaboration with traditional healers with an informative role. Such a program should address stigma and discrimination towards PWE as well as appropriate management of epilepsy.

Figure 1 :

 1 Figure 1: Location of the 3 pilot villages, the research headquarters and of the CT scan facility (Map adapted from http:// www.insd.bf/)

Acknowledgments

We would like to express our gratitude to Chantal Millogo for collecting the data and Léopold Bado for the translation and back translation from French to Lyele. Special thanks to Dr L. Raphaël Nébié and Elie Sawadogo and to all the members of the three villages for their warm welcome and their active participation to the study. This study was funded by the National Institute for Neurological Disorders and Stroke (NINDS) and the Fogarty International Center (FIC) of the US National Institutes of Health (Epidemiology and Burden of Neurocysticercosis in Burkina Faso) (R21 NS055353) as part of the Brain Disorders in the Developing World: Research Across the Life Span (BRAIN) grant program. The funders had no role in study design, collection data and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest statement:

The authors have no conflict of interest to declare.

Conflict of interest

None of the authors has any conflict of interest to disclose