Robust envelope exchange platform for oncolytic measles virus.

The use of oncolytic viruses (OV) to precisely target and eliminate tumors ('virotherapy') is a rapidly evolving therapeutic approach to treating cancer. A major obstacle in virotherapy, especially for systemic administration, is the host's immune response towards the OV. In the case of measles virus (MeV), most individuals have been immunized against this agent leading to pre-existing neutralizing antibodies that can impair OV delivery to the tumor. These antibodies predominantly target the hemagglutinin (H) and fusion (F) envelope glycoproteins displayed at the particle's surface. Here, we introduce a novel and versatile pseudotyping platform for rapid envelope exchange of oncolytic MeV that allows for engineering of chimeric viruses invulnerable to pre-existing anti-MeV antibodies. Using this system, we have successfully exchanged the MeV F and H proteins with the glycoprotein G of vesicular stomatitis virus (VSV) and the surface proteins of Newcastle disease virus (NDV) or canine distemper virus (CDV), all of which are not endemic in the general human population. While the MeV-VSV and MeV-NDV pseudotypes were non-functional, the MeV-CDV pseudotype was successfully propagated to high-titer virus stocks. This study describes the successful generation of a robust envelope exchange platform for oncolytic MeV while also highlighting its intricate pseudotyping tolerance.

[Overview of visual impairment at the Yalgado Ouédraogo University Medical Center: Study of 501 cases]. / Les profils de la déficience visuelle au centre hospitalier universitaire Yalgado Ouédraogo : à propos de 501 cas.

OBJECTIVE: To determine the main causes of visual impairment according to age in patients admitted to the ophthalmology department. MATERIALS AND METHODS: This was a retrospective study of 501 cases of visual impairment. Included were patients of both sexes whose best-corrected visual acuity in the better eye was strictly less than 5/10. The parameters studied were age, gender, place of residence, corrected visual acuity in the better eye, and diagnosis. The data were entered and processed with the Epi info 7.2 software. RESULTS: Subjects over 50 were the most prevalent (48.5%). In patients over 50 years of age, cataracts (54.32%) were the leading cause of visual impairment, followed by glaucoma (24.69%) and non-glaucomatous optic neuropathy (26.19%). Trauma (17.62%) was frequently found in patients aged 16 to 50 years. Tropical endemic limbo-conjunctivitis (25.00%) was the leading cause of visual impairment in subjects aged 5 to 15 years. CONCLUSION: This study confirms the results of the literature, which have shown that cataracts are the leading cause of visual impairment in developing countries. A major effort to raise awareness, provide information and therapeutic care would reduce the incidence of visual impairment.

[Preliminary selective laser trabeculoplasty (SLT) intraocular pressure results in glaucoma patients in Burkina Faso]. / Résultats tonométriques préliminaires de la trabéculoplastie sélective au laser (SLT) chez les glaucomateux au Burkina Faso.

INTRODUCTION: Glaucoma is the leading cause of irreversible blindness in the world. The purpose of our study was to evaluate the tonometric results of SLT treatment in patients with glaucoma. MATERIALS AND METHODS: This was a prospective study of patients with glaucoma who were seen from October 1, 2017 to July 31, 2018. All patients underwent SLT of the inferior 180°. Intraocular pressure (IOP) was measured before and then at 1, 15, 30, 60, 90 and 120days after treatment. RESULTS: We studied 35 eyes of 31 patients. The mean age was 59.3 (±8.4years), range 43-77years. The mean IOP prior to SLT was 20.1mmHg (±7mmHg). One day after the laser, this decreased to 17.6mmHg (±8.4), for a percentage of drop of 12.4%. At 30days, it was 15.3mmHg (±5.4mmHg), i.e. a 23.9% decrease. After 60 and 90days, there was a drop of 13.9% and 15.4%, respectively. At 120days, 43.3% of treated eyes had a decrease of at least 20%. The main complication was increased IOP in 14.2% of cases. CONCLUSION: SLT reduces IOP and the number of glaucoma medications in patients. It appears to be a viable alternative in our countries. These results should be confirmed with a larger cohort and longer follow-up.

[Causes of childhood blindness and visual impairment in Ouagadougou: About 398 cases]. / Causes de cécité et déficiences visuelles chez l'enfant à Ouagadougou : à propos de 398 cas.

INTRODUCTION: Childhood blindness is a public health problem in developing countries. The goal of this study was to focus on the epidemiological and clinical patterns of moderate to severe, uni- or bilateral childhood blindness and severe visual impairment in the ophthalmology department of Yalgado Ouedraogo university hospital (YOUH) in Ouagadougou, Burkina Faso. MATERIALS AND METHODS: We conducted a descriptive, cross-sectional analytic study based on retrospective data in the ophthalmology department of YOUH from January 1, 2010 to December 31, 2014. It included cases of childhood blindness and severe visual impairment (World Health Organisation: WHO) in children 0-15 years of age. The studied variables were sociodemographic and clinical data, visual outcomes, and avoidable aspects of their blindness (WHO). RESULTS: The prevalence of uni- or bilateral childhood blindness and severe visual impairment was 4.36% (398 cases out of 9125 children). The male/female ratio was 1.70. The mean age was 9±4 years old; 54% of children were school-age boys and girls; the most frequent causes among the 398 patients were traumatic (46.98%), infectious (12.31%) or congenital (10.05%). Most of the ocular injuries occured in boys (P<0.05) and school children (P<0.05). The injured structures resulting in childhood visual impairment were primarily the lens (30.65%) and the globe (27.64%). Childhood blindness and severe visual impairment were considered avoidable in 80.65% of cases. The type of visual disability was related to age, especially school age (P<0.0001) and to avoidability (P<0.05). CONCLUSION: Given the high prevalence of childhood blindness and severe visual impairment, early, effective management and preventive strategies should be employed.

[What do we know about diabetic retinopathy at the Sourô Sanou university medical center in Bobo-Dioulasso (CHUSS)?] / Que savons-nous de la rétinopathie diabétique au centre hospitalier universitaire Sourô Sanou de Bobo-Dioulasso (CHUSS) ?

INTRODUCTION: Ocular damage is one of the numerous complications of diabetes. Proliferative diabetic retinopathy can result in blindness. The purpose of our work was to study the aspects of diabetic retinopathy on fundus examination in diabetic patients in Bobo-Dioulasso in a hospital environment. METHODS: This is a descriptive, cross-sectional, prospective study from March 1st to August 31st 2014 of diabetic patients in the Sourô Sanou university hospital. We used the Francophone Diabetes Society's classification. RESULTS: We included 246 patients (487 eyes). The frequency of diabetic retinopathy (DR) was 47.1%, and the frequency of diabetic maculopathy 8.9%. Proliferative DR and severe Non-Proliferative DR represented 3.3% of eyes, and blindness occurred in 3%. Among diabetics with DR, the mean age was 55.75 years (standard deviation 11.04 years); the median duration of diabetes was 36 months, and 99.1% of the diabetic patients were categorized as type 2. There was a statistically significant association between diabetic retinopathy and duration of diabetes progression, history of neuropathy, presence of proteinuria on 24hour urines, hypercreatininemia, and also between triglyceride levels and diabetic maculopathy. CONCLUSION: Diabetic retinopathy affects almost half of diabetic patients at the Sourô Sanou university hospital. An earlier, multidisciplinary management approach might prevent this.

Success factors for implementing and sustaining a mature electronic medical record in a low-resource setting: a case study of iSanté in Haiti.

Electronic health information systems, including electronic medical records (EMRs), have the potential to improve access to information and quality of care, among other things. Success factors and challenges for novel EMR implementations in low-resource settings have increasingly been studied, although less is known about maturing systems and sustainability. One systematic review identified seven categories of implementation success factors: ethical, financial, functionality, organizational, political, technical and training. This case study applies this framework to iSanté, Haiti's national EMR in use in more than 100 sites and housing records for more than 750 000 patients. The author group, consisting of representatives of different agencies within the Haitian Ministry of Health (MSPP), funding partner the Centers for Disease Control and Prevention (CDC) Haiti, and implementing partner the International Training and Education Center for Health (I-TECH), identify successes and lessons learned according to the seven identified categories, and propose an additional cross-cutting category, sustainability. Factors important for long-term implementation success of complex information systems are balancing investments in hardware and software infrastructure upkeep, user capacity and data quality control; designing and building a system within the context of the greater eHealth ecosystem with a plan for interoperability and data exchange; establishing system governance and strong leadership to support local system ownership and planning for system financing to ensure sustainability. Lessons learned from 10 years of implementation of the iSanté EMR system are relevant to sustainability of a full range of increasingly interrelated information systems (e.g. for laboratory, supply chain, pharmacy and human resources) in the health sector in low-resource settings.

Epidemiological profile of patients with uveitis in Boko and Parakou, in northern Bénin.

To describe the epidemiology of uveitis in northern Bénin. This retrospective study carried out from records describing 10 years of uveitis care in 2 eye clinics in northern Bénin. The sample of 623 eyes with uveitis in 489 patients accounted for 1.0% of all consultations. A male predominance was observed with a sex-ratio of 1.5 (297 m/192 F). The patients' mean age was 35.7 ± 16.1 years, and the age range most often affected was 20-39 years. The uveitis was anterior in 32.3 %, posterior in 29.0 %, intermediate in 28.1% and total (panuveitis) in 10.6%. The cause was undetermined in 85.7 % of cases and identified in 14.3%, including toxoplasmosis in 47 cases (7.5%) and herpes zoster in 20 cases (3.2%). Outpatients accounted for all cases, and all received topical corticosteroids. Some complications were observed. Uveitis has a prevalence rate of 1% in northern Bénin. It caused blindness in 9.8% of affected eyes and impaired vision in 49.3%.

Clonal variation in interferon response determines the outcome of oncolytic virotherapy in mouse CT26 colon carcinoma model.

In our earlier studies, Semliki Forest virus vector VA7 completely eliminated type I interferon (IFN-I)-unresponsive human U87-luc glioma xenografts, whereas interferon-responsive mouse gliomas proved refractory. Here, we describe in two clones of CT26 murine colon carcinoma, opposed patterns of IFN-I responsiveness and sensitivity to VA7. Both CT26WT and CT26LacZ clones secreted biologically active interferon in vitro upon virus infection but only CT26WT cells were protected. Focal infection of CT26WT cultures was self-limiting but could be rescued using IFN-I pathway inhibitor Ruxolitinib or antibody against IFNß. Whole transcriptome sequencing (RNA-Seq) and protein expression analysis revealed that CT26WT cells constitutively expressed 56 different genes associated with pattern recognition and IFN-I signaling pathways, spanning two reported anti-RNA virus gene signatures and 22 genes with reported anti-alphaviral activity. Whereas CT26WT tumors were strictly virus-resistant in vivo, infection of CT26LacZ tumors resulted in complete tumor eradication in both immunocompetent and severe combined immune deficient mice. In double-flank transplantation experiments, CT26WT tumors grew despite successful eradication of CT26LacZ tumors from the contralateral flank. Tumor growth progressed uninhibited also when CT26LacZ inoculums contained only a small fraction of CT26WT cells, demonstrating dominance of IFN responsiveness when heterogeneous tumors are targeted with interferon-sensitive oncolytic viruses.

[What remains today of neonatal conjunctivitis in prefecture of Kozah in Togo?]. / Que reste-t-il aujourd'hui des conjonctivites néonatales dans la préfecture de la Kozah au Togo ?

AIM: The purpose of this study is to screen the neonatal conjunctivitis in order to evaluate its incidence and especially to seek for the causative germs. PATIENTS AND METHODS: We have realized cross-sectional study in three health centers of the prefecture of Kozah from March 24 to May 12, 2009. All the newborns followed in these centers are examined in the search of signs of conjunctivitis. A biological diagnosis of conjunctival secretions was carried out at the suspect newborns. RESULTS: During the study period, 348 newborns were examined including 185 boys and 163 girls corresponding to a sex-ratio (M/F) of 1.1. The middle age was 3.7 days. Twenty-eight newborns presented conjunctivitis, that is to say a rate of incidence of 8%. The cases of conjunctivitis were observed the first four days of life in 39.3% of cases. Eighteen of the newborns presenting conjunctivitis were vaginal deliveries (64.3%) against ten (35.7%) by caesarian. All the mothers of the ill newborns had a syndrome of sexually transmissible infection (STI) during the third quarters of pregnancy. After biological diagnosis, Staphylococcus aureus was found in 25% of the cases. CONCLUSION: Despite the common herd of neonatal conjunctivitis prophylaxis by Crede's method, its remains in the prefecture of Kozah. In hope for neonatal conjunctivitis eradication, treatment of STI on pregnant women associated to education and communication on the prevention of the infection in neonatal health care centers and at home by hygiene rule application are necessary.

[Eales disease: a case report in Burkina Faso]. / Maladie de Eales : à propos d'un cas au Burkina Faso.

The authors report the first case of Eales disease described in Burkina Faso. A 21-year-old man presented myodesopsia with acute visual acuity decrease in the right eye at 1/50, vitreous haemorrhage, and retinal phlebitis of the large trunks. In the left eye, visual acuity was 10/10 P2, with phlebitis associated with retinal haemorrhages, vascular occlusion, and retinal ischaemia. Laboratory investigations found a positive TST at 20mm but the Koch bacillus was not isolated. The patient received treatment for tuberculosis, corticosteroids, retinal argon laser photocoagulation, and vitrectomy in the right eye. The clinical, immunopathological, and therapeutic aspects of Eales disease are discussed.

Etude radiologique des retinoblastomes en milieu africain burkinabe

Objectif : Decrire les aspects radiologiques du retinoblastome et analyser l'apport de l'imagerie medicale dans cette affection en milieu africain burkinabe. Methode : Etude retrospective menee entre janvier 2005 et decembre 2008; incluant 15 cas suspects de retinoblastome apres exploration par echographie et tomodensitometrie (TDM). Resultats : Le groupe comprenait 9 garcons et 6 filles; d'age median de 2;2 ans. Le retinoblastome etait de forme exophytique; unilateral chez 11 patients (73;3) et bilateral dans 4 cas (26;7). Les calcifications intratumorales etaient retrouvees dans 93;3des cas a l'echographie. Le scanner precisait les extensions loco-regionales et a permis de decouvrir deux cas de retinoblastomes trilateraux. Conclusion : La TDM demeure la technique la mieux appropriee pour le diagnostic du retinoblastome en imagerie. Son cout eleve constitue une limite a son accessibilite dans la plupart des pays pauvres. L'echographie peut etre une alternative lorsque des calcifications intratumorales sont mises en evidence

[Contribution of indocyanine green angiography in sickle cell retinopathy]. / Apport de l'angiographie au vert d'indocyanine dans la rétinopathie drépanocytaire.

PURPOSE OF THE STUDY: This was a prospective, nonrandomized observational study to search for choroidal abnormalities associated with sickle cell retinopathy and to assess the contribution of indocyanine green angiography (ICG) in this disease. PATIENTS AND METHOD: From July to October 2000, 26 patients with sickle cell disease (SS, SC, and thalassemia) were recruited, most followed in the pediatric department. After an ophthalmologic clinical examination, fluorescein angiography and indocyanine green angiography(ICG) were performed. RESULTS: The average age was 14.3 years (range, 9-24 years). There were 17 SS forms (65.4%), five SC forms (19.2%), and four beta-thalassemia forms (15.4%). The ICG was well tolerated. In 24 cases (92.3%), we observed rarefaction of the choriocapillaris out of the posterior pole with no difference depending on the genotype. We noted neither hypo- nor hyperfluorescence of the choroid at the retinal ischemic areas, the black spots were clearly delimited, and photocoagulation scars appeared larger than in fluorescein angiography. DISCUSSION: Our ICG study did not show anomalies of the choroidal circulation but rarefaction of the choriocapillaris was observed in most patients, a striking finding. This lower visibility or nonperfusion could be explained by anatomical modifications or by a centripetal reduction in the density of the choriocapillaris concomitant to the microvascular occlusive phenomena in the ischemic retina. CONCLUSION: This study is the first to use ICG in sickle cell retinopathy. The rarefaction of the choriocapillaris observed may be related to the systemic disease. However, it must be compared with the choriocapillaris of normal subjects at the same age.

[Epidemiology and prognostic factors for sickle cell retinopathy in Ouagadougou (Burkina Faso)]. / Etude épidémiologique et facteurs pronostiques de la rétinopathie drépanocytaire à Ouagadougou (Burkina Faso).

INTRODUCTION: The frequency of sickle cell disease varies from 5% to 20% in Africa. PATIENTS AND METHOD: This retrospective study investigated 173 patients in an ambulatory setting from August 2000 to July 2006. The study included 98 women and 75 men, aged 15-62 years, with a mean age of 26.7 years. RESULTS: Only 89 patients (71 SC and 18 SS) were seen in ophthalmology, 44 (49%) had sickle cell retinopathy with 26 (29%) cases nonproliferative and 18 cases proliferative (20%). Among the 71 SC patients, 35 (50%) had sickle cell retinopathy, with 40% the proliferative form. Of the 18 SS patients, nine had a retinopathy (50%), with four cases proliferative. DISCUSSION: Retinopathy is a frequent complication of sickle cell disease, which can lead to blindness, and its management better accessibility to the ophthalmologic examination and preventive treatment by laser photo coagulation.

[Lacquer cracks complicated with choroidal neovascularization in pseudoxanthoma elasticum: the first case report in Burkina Faso]. / Stries angioïdes compliquées de néovascularisation choroïdienne dans le cadre d'un pseudoxanthome élastique: 1er cas décrit au Burkina Faso.

Lacquer cracks are breaks in the Bruch membrane by alteration of the elastic layer. They are often associated with pseudoxanthoma elasticum. The authors report the first case in Burkina Faso involving a 51-year-old woman who was seen for visual acuity loss. She had pseudoxanthoma elasticum associated with lacquer cracks complicated by choroidal neovascularization in both eyes. She was treated with laser photocoagulation of the neovessels in the left eye, and no recurrence was reported after 6 months.

Enhanced killing of androgen-independent prostate cancer cells using inositol hexakisphosphate in combination with proteasome inhibitors.

Effective treatments for androgen-independent prostate cancer (AIPCa) are lacking. To address this, emerging therapeutics such as proteasome inhibitors are currently undergoing clinical trials. Inositol hexakisphosphate (IP6) is an orally non-toxic phytochemical that exhibits antitumour activity against several types of cancer including PCa. We have previously shown that treatment of PC3 cells with IP6 induces the transcription of a subset of nuclear factor-kappaB (NF-kappaB)-responsive and pro-apoptotic BCL-2 family genes. In this study, we report that although NF-kappaB subunits p50/p65 translocate to the nucleus of PC3 cells in response to IP6, inhibition of NF-kappaB-mediated transcription using non-degradable inhibitor of kappaB (IkappaB)-alpha does not modulate IP6 sensitivity. Treatment with IP6 also leads to increased protein levels of PUMA, BIK/NBK and NOXA between 4 and 8 h of treatment and decreased levels of MCL-1 and BCL-2 after 24 h. Although blocking transcription using actinomycin D does not modulate PC3 cell sensitivity to IP6, inhibition of protein translation using cycloheximide has a significant protective effect. In contrast, blocking proteasome-mediated protein degradation using MG-132 significantly enhances the ability of IP6 to reduce cellular metabolic activity in both PC3 and DU145 AIPCa cell lines. This effect of combined treatment on mitochondrial depolarisation is particularly striking and is also reproduced by another proteasome inhibitor (ALLN). The enhanced effect of combined MG132/IP6 treatment is almost completely inhibited by cycloheximide and correlates with changes in BCL-2 family protein levels. Altogether these results suggest a role for BCL-2 family proteins in mediating the combined effect of IP6 and proteasome inhibitors and warrant further pre-clinical studies for the treatment of AIPCa.

Cervicovaginal secretory antibodies to human immunodeficiency virus type 1 (HIV-1) that block viral transcytosis through tight epithelial barriers in highly exposed HIV-1-seronegative African women.

Antibodies to human immunodeficiency virus (HIV) of the IgA, IgG, and IgM isotypes and high levels of the HIV suppressive beta-chemokine RANTES (regulated on activation, normally T cell expressed and secreted) were found in the cervicovaginal secretions (CVSs) of 7.5% of 342 multiply and repeatedly exposed African HIV-seronegative female sex workers. The antibodies are part of a local compartmentalized secretory immune response to HIV, since they are present in vaginal fluids that are free of contaminating semen. Cervicovaginal antibodies showed a reproducible pattern of reactivity restricted to gp160 and p24. Locally produced anti-env antibodies exhibit reactivity toward the neutralizing ELDKWA epitope of gp41. Study results show that antibodies purified from CVSs block the transcytosis of cell-associated HIV through a tight epithelial monolayer in vitro. These findings suggest that genital resistance to HIV may involve HIV-specific cervicovaginal antibody responses in a minority of highly exposed HIV-seronegative women in association with other protecting factors, such as local production of HIV-suppressive chemokines.

Detection of Y chromosome DNA as evidence of semen in cervicovaginal secretions of sexually active women.

The detection of traces of semen in cervicovaginal secretions (CVS) from sexually active women practicing unprotected sex is a prerequisite for the accurate study of cervicovaginal immunity. Two semen markers, the prostatic-specific antigen (PSA) and the Y chromosome, were detected in parallel in CVS obtained by a standardized vaginal washing of consecutive women attending the principal medical center for sexually transmitted diseases of Bangui, Central African Republic. PSA was detected by immunoenzymatic capture assay in the cell-free fraction of CVS, and the Y chromosome was detected by a single PCR assay of DNA extracted by silica from the cell fraction (Y PCR). Fifty (19%) cell-free fractions of the 264 beta-globin-positive CVS samples were positive for PSA, and 100 (38%) cell fractions of the CVS samples were positive for the Y chromosome. All the 50 (19%) PSA-containing CVS samples were also positive for the Y chromosome. Fifty (19%) CVS samples were positive only for the Y chromosome, with no detectable PSA. The remaining 164 (62%) CVS samples were both PSA and Y chromosome negative. These findings demonstrate that CVS from sexually active women may contain cell-associated semen residues unrecognized by conventional immunoenzymatic assays used to detect semen components. The detection of cell-associated male DNA with a highly sensitive and specific procedure such as Y PCR constitutes a method of choice to detect semen traces in female genital secretions.

[Congenital rubella: a case report]. / Rubéole congénitale : à propos d'un cas.

Rubella is an innocuous illness in adult unless it is contracted by a pregnant woman. We recently observed a case of congenital rubella in the department of neonatology of Abass Ndao hospital in Dakar. It's a female new-born, born after 40 week gestation, with a well followed pregnancy. The first clinical examination shows a severe intrauterine growth retardation and bilateral comeal opacity. Maternal and new-born serologic confirmation is obtained with positive rubella specific IgM and IgG. We also find severe ocular pathology, hearing deficit and associated cardiac disease. This case shows the needs for preventive strategies, such as vaccination against rubella for women of child bearing age.

Neutralizing antibodies and complement-mediated, antibody-dependent enhancement (C'-ADE) of human immunodeficiency virus infection in its vertical transmission.

PROBLEM: Mother-to-child transmission is a major route for the spread of human immunodeficiency virus (HIV) worldwide. Our understanding of its mechanisms and parameters is still limited. Among the factors possibly involved in virus passage determination are the level and quality of antiviral humoral response. METHOD OF STUDY: Anti-HIV-1/Lai neutralizing activity in sera from 35 mother-infant pairs (in which 13 transmission cases occurred) was investigated, as was the complement-mediated antibody-dependent enhancement capacity of the same sera. RESULTS: Neutralization titers of 640 or more were found only in four mothers of uninfected children, but this result was not significant. No significant link was obtained with the occurrence of complement-mediated, antibody-dependent enhancement. CONCLUSIONS: As suggested by a synthesis of the literature, vertical transmission of HIV is probably the result of multiple active and/or stochastic parameters in the mother, the fetal structures, and the viral population. The precise definition of cellular mechanisms involved in in utero infection would help to better define which immune activity in the mother should be more carefully considered.