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Copyright of Mali Médical is the property of Mali Medical, Faculte de Medecine, de Pharmacie et d'Odonto-stomatologie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Mali Médical is the property of Mali Medical, Faculte de Medecine, de Pharmacie et d'Odonto-stomatologie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Mali Médical is the property of Mali Medical, Faculte de Medecine, de Pharmacie et d'Odonto-stomatologie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. Little is known about the determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing., Methods: We analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint., Results: We observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. We also noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points., Conclusion: This study highlights the importance of baseline immune signatures in determining disease outcome. Our data suggests that differences in apoptotic and inflammatory gene expression patterns can serve as predictive markers of susceptibility to clinical malaria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mbambo, Dwivedi, Ifeonu, Munro, Shrestha, Bromley, Hodges, Adkins, Kouriba, Diarra, Niangaly, Kone, Coulibaly, Traore, Dolo, Thera, Laurens, Doumbo, Plowe, Berry, Travassos, Lyke and Silva.)

Host immunity has been suggested to clear drug-resistant parasites in malaria-endemic settings. However, the immunogenetic mechanisms involved in parasite clearance are poorly understood. Characterizing the host's immunity and genes involved in controlling the parasitic infection can inform the development of blood-stage malaria vaccines. This study investigates host regulatory cytokines and immunogenomic factors associated with the clearance of Plasmodium falciparum carrying a chloroquine resistance genotype. Biological samples from participants of previous drug efficacy trials conducted in two Malian localities were retrieved. The P. falciparum chloroquine resistance transporter (Pfcrt) gene was genotyped using parasite DNA. Children carrying parasites with the mutant allele (Pfcrt-76T) were classified based on their ability to clear their parasites. The levels of the different cytokines were measured in serum. The polymorphisms of specific human genes involved in malaria susceptibility were genotyped using human DNA. The prevalence of the Pfcrt-76T was significantly higher in Kolle than in Bandiagara (81.6 % vs 38.6 %, p < 10 -6 ). The prevalence of children who cleared their mutant parasites was significantly higher in Bandiagara than in Kolle (82.2 % vs 67.4 %, p < 0.05). The genotyping of host genes revealed that IFN-γ -874 T and TNF-α -308A alleles were positively associated with parasite clearance. Cytokine profiling revealed that IFN-γ level was positively associated with parasite clearance (p = 0.04). This study highlights the role of host's immunity and immunogenetic factors to clear resistant parasites, suggesting further characterization of these polymorphisms may help to develop novel approaches to antiparasitic treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Introduction: The health district of Mopti is confronted with factors that influence its vaccination coverage [1]. The aim of the study was to study the factors influencing the low BCG vaccination coverage in VAR1 and Penta3 in children aged 0 to 23 months in the health district in 2021., Methodology: We carried out a descriptive cross-sectional study, collected information from 280 mothers questioned on the services provided by the vaccination service for children before the age of two, the reasons for incompleteness using a questionnaire. Univariate and multivariate logistic regression analysis was done for the variables using SPSS software. An association was significant when p < 0.05., Results: Vaccination completeness was 53.08%, varying from 94% BCG, 79% VAR1 and 83% Penta3. The analysis showed that mothers who spent more time at the vaccination center (P=0.098, Chi-square=18.617), who missed certain sessions (P=0.174, Chi-square=13.371) and who were informed of missed consumables (P=0.278, Chi-square= 7.485) are significantly associated with vaccine incompleteness., Conclusion: Vaccination completeness was insufficient despite good knowledge of the mothers on vaccination., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

To determine a demographic overview of orthopoxvirus seroprevalence, we tested blood samples collected during 2003-2019 from France (n = 4,876), Bolivia (n = 601), Laos (n = 657), and Mali (n = 255) for neutralizing antibodies against vaccinia virus. In addition, we tested 4,448 of the 4,876 samples from France for neutralizing antibodies against cowpox virus. We confirmed extensive cross-immunity between the 2 viruses. Seroprevalence of antibodies was <1% in Bolivia, <5% in Laos, and 17.25% in Mali. In France, we found low prevalence of neutralizing antibodies in persons who were unvaccinated and vaccinated for smallpox, suggesting immunosenescence occurred in vaccinated persons, and smallpox vaccination compliance declined before the end of compulsory vaccination. Our results suggest that populations in Europe, Africa, Asia, and South America are susceptible to orthopoxvirus infections, which might have precipitated the emergence of orthopoxvirus infections such as the 2022 spread of monkeypox in Europe.

Background: In malaria endemic countries, seasonal malaria chemoprevention (SMC) interventions are performed during the high malaria transmission in accordance with epidemiological surveillance data. In this study we propose a predictive approach for tailoring the timing and number of cycles of SMC in all health districts of Mali based on sub-national epidemiological surveillance and rainfall data. Our primary objective was to select the best of two approaches for predicting the onset of the high transmission season at the operational scale. Our secondary objective was to evaluate the number of malaria cases, hospitalisations and deaths in children under 5 years of age that would be prevented annually and the additional cost that would be incurred using the best approach., Methods: For each of the 75 health districts of Mali over the study period (2014-2019), we determined (1) the onset of the rainy season period based on weekly rainfall data; (ii) the onset and duration of the high transmission season using change point analysis of weekly incidence data; and (iii) the lag between the onset of the rainy season and the onset of the high transmission. Two approaches for predicting the onset of the high transmission season in 2019 were evaluated., Results: In the study period (2014-2019), the onset of the rainy season ranged from week (W) 17 (W17; April) to W34 (August). The onset of the high transmission season ranged from W25 (June) to W40 (September). The lag between these two events ranged from 5 to 12 weeks. The duration of the high transmission season ranged from 3 to 6 months. The best of the two approaches predicted the onset of the high transmission season in 2019 to be in June in two districts, in July in 46 districts, in August in 21 districts and in September in six districts. Using our proposed approach would prevent 43,819 cases, 1943 hospitalisations and 70 deaths in children under 5 years of age annually for a minimal additional cost. Our analysis shows that the number of cycles of SMC should be changed in 36 health districts., Conclusion: Adapting the timing of SMC interventions using our proposed approach could improve the prevention of malaria cases and decrease hospitalisations and deaths. Future studies should be conducted to validate this approach., (© 2022. The Author(s).)

Introduction: The linea alba is the second most frequent site of abdominal wall hernias after the inguinal region. Prosthetic approach, often recommended, comes up against the low socio-economic level and the availability of these materials in developing countries. Our objective is to evaluate the indications and results of midline ventral hernia surgery., Methods: This was a retrospective cross-sectional study over 36 months including all adult patients (over 15 years old) treated for primary or recurrent midline ventral hernias. The parameters studied were: age, sex, risk factors, type of hernia according to the classification of the European Hernia Society (EHS), clinical presentation, hernial ring size, surgical technique and results (recurrence, chronic pain)., Results: We included 65 patients. The mean age was 40.5 years ± 16.4. There was a female predominance (56.3%, n = 36) with a sex ratio of 0.77. According to the EHS classification, type M3 (umbilical) was more common (67.2%), followed by type M2 (epigastric) in 25% and M4 (infra-umbilical) in 1.6%. According to the clinical presentation, 85.6% (n = 55) were uncomplicated, 10.9% (n = 7) were strangulated in and 3.1% (n = 2) incarcerated. A primary suture was performed in 93.8% (n = 61) and a mesh repair in 6.15% (n = 4). With a mean follow-up of 8.2 ± 11.9 months, we noted a recurrence in 6.1% (n = 4) and chronic pain in 6.1% (n = 4)., Conclusion: There is a need to individualize or contextualize the guidelines. In our context where meshes are not always available, pure tissue repairs keep their place in the treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Cancer incidence and mortality rates are increasing in West Africa. Cancer is a recent discipline in Mali and the means available to treat patients are insufficient. Mali has only one radiotherapy machine for the country and its malfunctions are regularly reported in the media. In order to understand the recurrent dissatisfactions linked to access to radiotherapy in Mali, we retraced the history of this machine and described its functioning. Based on semi-directive interviews with patients&#8217; associations and health professionals involved in cancer care in Bamako, we describe how radiotherapy in Mali reveals global health issues through the intervention of numerous international cooperations. In addition, based on data collection from medical registers and institutional reports, we report that the average time to get a radiotherapy appointment is 3 to 6 months in Mali, but also that the radiotherapy machine has experienced 198 breakdowns between April 3, 2014 and September 24, 2021, which represents more than 54&#160;weeks of cumulative downtime. Radiotherapy is a crucial element in the treatment of cancer and the lack of access to this treatment worsens the vital diagnosis of patients. While the Malian government is committed to universal health coverage reforms, strengthening cancer treatment facilities should also be considered a public health priority for Mali.

var genes encode Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) antigens. These highly diverse antigens are displayed on the surface of infected erythrocytes and play a critical role in immune evasion and sequestration of infected erythrocytes. Studies of var expression using non-leukocyte-depleted blood are challenging because of the predominance of host genetic material and lack of conserved var segments. Our goal was to enrich for parasite RNA, allowing de novo assembly of var genes and detection of expressed novel variants. We used two overall approaches: (i) enriching for total mRNA in the sequencing library preparations and (ii) enriching for parasite RNA with a custom capture array based on Roche's SeqCap EZ enrichment system. The capture array was designed with probes based on the whole 3D7 reference genome and an additional >4,000 full-length var gene sequences from other P. falciparum strains. We tested each method on RNA samples from Malian children with severe or uncomplicated malaria infections. All reads mapping to the human genome were removed, the remaining reads were assembled de novo into transcripts, and from these, var -like transcripts were identified and annotated. The capture array produced the longest maximum length and largest numbers of var gene transcripts in each sample, particularly in samples with low parasitemia. Identifying the most-expressed var gene sequences in whole-blood clinical samples without the need for extensive processing or generating sample-specific reference genome data is critical for understanding the role of PfEMP1s in malaria pathogenesis. IMPORTANCE Malaria parasites display antigens on the surface of infected red blood cells in the human host that facilitate attachment to blood vessels, contributing to the severity of infection. These antigens are highly variable, allowing the parasite to evade the immune system. Identifying these expressed antigens is critical to understanding the development of severe malarial disease. However, clinical samples contain limited amounts of parasite genetic material, a challenge for sequencing efforts further compounded by the extreme diversity of the parasite surface antigens. We present a method that enriches for these antigen sequences in clinical samples using a custom capture array, requiring minimal processing in the field. While our results are focused on the malaria parasite Plasmodium falciparum, this approach has broad applicability to other highly diverse antigens from other parasites and pathogens such as those that cause giardiasis and leishmaniasis.

We call into question the established dogma that viruses with envelopes and RNA genomes have limited stability by demonstrating the staggering long-term viability, ∼2 years, of chikungunya virus when stored in liquid environments at +4°C in the dark. We contend that our understanding of the infectivity of a variety of enveloped viruses requires a new approach to identify under standardized conditions the primary determinants of their viability.

Serological surveys are essential to quantify immunity in a population but serological cross-reactivity often impairs estimates of the seroprevalence. Here, we show that modeling helps addressing this key challenge by considering the important cross-reactivity between Chikungunya (CHIKV) and O'nyong-nyong virus (ONNV) as a case study. We develop a statistical model to assess the epidemiology of these viruses in Mali. We additionally calibrate the model with paired virus neutralization titers in the French West Indies, a region with known CHIKV circulation but no ONNV. In Mali, the model estimate of ONNV and CHIKV prevalence is 30% and 13%, respectively, versus 27% and 2% in non-adjusted estimates. While a CHIKV infection induces an ONNV response in 80% of cases, an ONNV infection leads to a cross-reactive CHIKV response in only 22% of cases. Our study shows the importance of conducting serological assays on multiple cross-reactive pathogens to estimate levels of virus circulation., (© 2021. The Author(s).)

A pot incubation experiment under natural conditions was designed to investigate the effects of three biodegradable chelating agents, namely; the [S,S]-isomer of ethylenediamine disuccinate (EDDS), citric acid (CA), and tetrasodium N,N-Bis(carboxymethyl)-L-glutamate acid (GLDA), on two plant species (Brassica juncea and Brassica rapa) in terms of plant foliar growth, dry matter yield, and heavy metal (HM) accumulation. Both plant species exhibited diminished growth and symptoms of phytotoxicity under HM stress. The application of EDDS and CA affected plant foliar growth, biomass production, and led to the development of chlorotic lesions on leaves. EDDS and CA also decreased the shoot length by 38.5% and 45.2% in B. juncea, and 60.1% and 100% in B. rapa, respectively. In contrast, GLDA relieved HM stress by significantly increasing plant growth (P > 0.05) and was shown to be well tolerated (tolerance index [TI]; B. juncea = 99% and B. rapa = 123%). Among both plants, B. juncea displayed the ability to accumulate a wider range of HMs at higher concentrations. Amongst the three chelators, EDDS induced the highest bioconcentration (BCF) of Pb (2.45), Zn (2.68), and Cd (3.36) while CA achieved better results for Ni (4.01) and Cr (1.45). However, the current results showed that even with the application of chelating agents, HMs were predominantly accumulated in roots and translocation factor was generally <1. The findings of this investigation emphasize that chelate-assisted phytoextraction with Brassica spp. is highly limited in multi-metal settings, making it an unsuitable option for severely contaminated sites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectif: The aim of this study was to describe the results of radiochemotherapy in patients after transurethral resection of muscle invasive bladder tumors., Material and Methods: A retrospective study from May 2014 to May 2016 in the radiotherapy department of the Mali Hospital. Have been included, all patients with bladder cancer infiltrating the muscle. Secondary cancers of the bladder and metastatic forms have been excluded from our study. Transurethral resection of bladder was performed. Neoadjuvant chemotherapy with paclitaxel- carboplatin was administered every three weeks in all patients, then external phototherapy 6 MV at a dose of 66 Gy due to 2 Gy of 5 sessions per week 6MV photon of external beam radiotherapy at a dose of 66 Gy due to 2 Gy of 5 sessions per week associated with concomitant cisplatin at dose of 40mg / m2 / week., Results: Eight patients were included in ourstudy. The average age of 53.75 ± 14.84 years. The male sex was predominant 87.5% (n = 7). The history of chronic smoking wasfound in four patients. The main carcinogenic risk factor identified in our patients was urogenital bilharzia (6 cases / 8).The histological type found was urothelial carcinomain 12.5% (n = 1) and invasive squamous cell carcinomain 87.5% (n = 7). Transurethral resection of the tumor was performed in 62.5% (n = 5). Endoscopic biopsy was performed in 37.5% (n = 3). The tumor was classified pT2N0M0 in 50% (n = 4), pT3aN0M0 in 37.5% (n = 3) and pT3bN0M0 in 12.5% (n = 1). Neoadjuvant chemotherapy with paclitaxel - carboplatin every three weeks was administered to all patients. The results of radiochemotherapy (see Table: evolution)., Conclusion: Concomitant radiochemotherapy is a conservative curative treatment that can be proposed as a replacement for cystectomy, for non-metastatic infiltrating tumors after the most complete endoscopic resection., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

Introduction: The objective of our study was to establish the epidemiological profile of COVID-19 in Tombouctou., Material and Methods: This was a descriptive cross-sectional study of COVID-19 surveillance data from Tombouctou from April 3 to October 1, 2020. Our variables of interest were extracted from the surveillance database and analyzed with Excel 2013. The frequencies, rate, and ratio were computed., Results: Overall, 1851 suspects from all districts of the region were screened by RT-PCR, including 572 confirmed, which indicate a positivity rate of 30.90%. The 15-34 age group was the most represented with 48% of the confirmed cases. The sex ratio (male / female) of confirmed cases was 2.67. The city of Tombouctou was the epicenter of COVID-19. The Tombouctou region had a detection rate of around 2‰ (1851/928,000) and peaked between weeks 22 and 23 with a case fatality of 2.8%., Conclusion: Young people and men were most likely to be infected with COVID-19. We recommend increasing awareness of compliance with barrier measures., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

Innovations in vaccine product attributes could play an important role in addressing coverage and equity (C&E) gaps, but there is currently a poor understanding of the full system impact and trade-offs associated with investing in such technologies, both from the perspective of national immunisation programmes (NIPs) and vaccine developers. Total Systems Effectiveness (TSE) was developed as an approach to evaluate vaccines with different product attributes from a systems perspective, in order to analyse and compare the value of innovative vaccine products in different settings. The TSE approach has been advanced over the years by various stakeholders including the Bill and Melinda Gates Foundation (BMGF), Gavi, PATH, UNICEF and WHO. WHO further developed the TSE approach to incorporate the country perspective into immunisation decision-making, in order for countries to evaluate innovative products for introduction and product switch decisions, and for vaccine development stakeholders to conduct their assessments of product value in line with country preferences. This paper describes the original TSE approach, development of the tool and processes for NIPs to apply the WHO TSE approach, and results from piloting in 12 countries across Africa, Asia and the Americas. The WHO TSE framework emerged from this piloting effort. The WHO TSE approach has been welcomed by NIP and vaccine development stakeholders as a useful tool to evaluate trade-offs between different products. It was emphasised that the concept of "total systems effectiveness" is likely to be context-specific and that TSE is valuable in facilitating a deliberative process to articulate NIP priorities, for decisions around product choice, and for prioritising the development of future vaccine innovations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Recent evidence suggests that proprotein convertase subtilisin/kexin type 9 (PCSK9), a downmodulator of cellular uptake of blood cholesterol, also negatively impacts host immune response to microbial infection. In this study, we investigated whether carrying the loss-of-function (LOF) rs562556 (c.1420 A > G; p.I474 V) PCSK9 single nucleotide polymorphism (SNP) affected the outcome of severe malaria in children. Archival DNA of a cohort of 207 Malian children suffering from severe malaria was genotyped for the rs562556 SNP. Sixty-four children were either heterozygous or homozygous for the minor G allele (carriers); 143 children were homozygous for the common A allele (noncarriers). Among carriers, there was one mortality case (1.6%), compared to 15 cases (10.5%) among noncarriers ( p =0.0251), suggesting that the G allele is associated with better survival in severe malaria. Intriguingly, this allele did not negatively segregate with any of the clinical symptoms linked to mortality in this cohort. Studies are needed to determine whether PCSK9 inactivation promotes a protective immune response to malaria infection., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Olesya Fedoryak et al.)

The circulation of Zika virus (ZIKV) in Mali has not been clearly characterized. Therefore, we conducted a serologic survey of 793 asymptomatic volunteers >15 years of age (2016), and 637 blood donors (2013) to assess the seroprevalence of ZIKV infection in 2 ecoclimatic regions of Mali, tropical savannah and warm semiarid region, using ELISA and seroneutralization assays. The overall seroprevalence was ≈12% and increased with age, with no statistical difference between male and female participants. In the warm semiarid study sites we detected immunological markers of an outbreak that occurred in the late 1990s in 18% (95% CI 13%-23%) of participants. In tropical savannah sites, we estimated a low rate of endemic transmission, with 2.5% (95% CI 2.0%-3.1%) of population infected by ZIKV annually. These data demonstrate the circulation of ZIKV in Mali and provide evidence of a previously unidentified outbreak that occurred in the late 1990s.

The trimellar pregnancy on bicicatricial uterus is a rare situation. It can be associated with many maternal-fetal complications. Given these risks, some teams opt for an embryonic reduction. We report a case of spontaneous trimellar pregnancy on bicicatricial uterus. This was a 38 year-old patient, third pregnancy, second birth, 2 alive with a history of 2 caesareans. The evolution of the pregnancy was marked by a urinary tract infection at 34 weeks of gestation. The caesarean section performed at 36 weeks of gestation allowed the birth of 3 newborns, 2 of which were females in 2000 and 1900 grams, and one male weighing 2400 grams. The postpartum was marked by a rapidly resolved eclampsia crisis., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

Aim: The aim was to compare the maternal-fetal prognosis of pregnancies in large multiparous with that of other parities., Materials and Methods: We conducted a case-control study from March 1 st , 2014 to February 1 st , 2015. It concerned all parturients admitted in our service during the study period. We have chosen 1 case for 2 witnesses. All the large multiparous were included as cases and as witnesses the primiparous, the pauciparous and the multiparous who gave birth just before and after the case. The statistical test was the Chi2 with a significance level at 5%., Results: The frequency of pregnancy in the large multiparous was 4.93%. They were housewives in 84% of cases, unschooled in 74.7% of cases. The maternal-fetal outcome was dominated by uterine rupture in 0.6% of cases, immediate postpartum hemorrhage in 9.8% of cases, vicious presentations in 5.5% of cases and cord prolapse in 6.8% of cases., Conclusion: Large multiparity is common in our practice. It is a high-risk pregnancy because of its many maternal-fetal complications., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

We report a rare case of polyostotic fibrous dysplasia with maxillofacial dysmorphia diagnosed in the radiology department at Hopital Sominé Dolo of Mopti. The aim was to describe the role of medical imaging including the CT scan in its diagnosis. He was a 42-year-old man of rural origin with poor socio-economic conditions. He was sent to us for a craniofacial CT scan for assessment of a maxillofacial mass. This CT scan showed a thickening of the diploid of the vault and the cranial base with osteocondensation and osteolytic lesions at the maxillofacial level. An extension assessment showed polyostotic involvement. His diagnosis is based on medical imaging and in particular CT scan. Three types of radiological aspects are evocative: a homogeneous or heterogeneous clarity, a smoke-like appearance and a slightly condensed appearance. Complications observed were deformities, fracture of the femoral neck and aesthetic damage., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

Goal: The goal was to assess the maternal-fetal prognosis of anemia in pregnant women in the Bougouni reference health center., Methods: We carried out a prospective descriptive and analytical cross-sectional study from January 1 to December 31, 2013 at the Bougouni reference health center. It covered all pregnant women with a hemoglobin level below 11g/dl regardless of the outcome of the pregnancy., Results: The prevalence of anemia in pregnant women was 33.2%. They were women married to peasants in 88.6% of cases, unschooled in 93.2% of cases, having not done antenal care in 56.8% of cases. Malaria was the most common etiology in 75% of cases. Anemia was severe in 61.4% of cases. The maternal-fetal prognosis was dominated by 3.3% of maternal death, 12.5% of abortion, 7.6% of prematurity and 6.8% of fetal death in utero., Conclusion: Anemia in pregnant women is the source of many maternal-fetal complications., (Le comité de rédaction se réserve le droit de renvoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de conserver un exemplaire du manuscrit, des figures et des tableaux.)

Urethral stricture is a disease whose cause and management vary according to the context. This study aims to analyze the epidemiological etiological and therapeutic features of urethral stricture in our department. We conducted a longitudinal cross-sectional study of patients with acquired urethral stricture admitted to our department between March 2014 and February 2016. The average age of our patients was 24.5 years (10 and 81years). The diagnosis was confirmed by retrograde and voiding Urethro-Cystography (UCG). The average stricture length was 2.28cm (0.5-5cm). The therapeutic approaches included: resection with termino-terminal anastomosis; retrograde dilatation etc. Outcome assessment performed 6-15 months after surgery was satisfactory with absence of recidivism, PMR ≤30cc and strong urine flow and weak in the case of recurrence of dysuria or PMR ≥100cc. Urethral stricture accounted for 7.14% of our urologic treatments. Most of our patients were farmers from the rural area. A history of recurrent urethritis was most often reported by our patients and 78,57% of them were married men, among whom 91% were polygamous). The main reason for consultation was dysuria (50% of the study population) and 50.01% of our patients had secondary urinary tract infection, most commonly caused by Escherichia coli. The main cause of urethral stricture was an infection (56.52%). The most affected area was the bulbar urethra (45.60% of cases). UCG was the most used technique (39.13%). Overall outcomes were good (85,65%) and failure rate reached 13.04%; the highest success rate was achieved with resection with anastomosis (94.44% respectively). Urethral stricture is common among young people. Infection is the main cause in our department. Prevention is essential as well as an efficient and effective management of sexually transmitted infections., Competing Interests: Les auteurs ne déclarent aucun conflit d'intérêts., (© Salifou Issiaka Traore et al.)

More than half of tuberculosis cases in the world are due to resuscitation of dormant Mycobacterium tuberculosis ( Mtb ) sequestered into cell-derived structures called granulomas. It is fairly admitted that cytokines and more particularly Tumor Necrosis Factor (TNF)-α is critical in the control of Mtb infections and that anti-TNF-α drugs constitute one of the main risk factors for reactivation of latent Mtb infection. The aim of this study was to evaluate the role of etanercept, a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human p75 TNF receptor linked to the Fc portion of human IgG1, in an in vitro model of human tuberculous granuloma. We showed that etanercept slightly delayed the formation of granuloma and reduced the generation of multinuclear giant cells (MGCs). In addition, etanercept exacerbated the expression of M1 polarization genes but also induced interleukin (IL)-10 release. In addition, our results indicated that etanercept inhibited cell fusion in an IL-10-dependent manner. Moreover, adalimumab, a human monoclonal anti-TNF-α IgG1 inhibited MGC formation in granuloma, without altering IL-10 secretion and induced macrophage apoptosis. Taken together, our data provides new insights into the role of TNF-α blockers in MGCs formation and the impact of such immunomodulatory drugs on tuberculous granuloma maturation.

Background: A malaria vaccine based on Plasmodium falciparum apical membrane antigen 1 (AMA1) elicited strain specific efficacy in Malian children that waned in the second season after vaccination despite sustained AMA1 antibody titers. With the goal of identifying a humoral correlate of vaccine-induced protection, pre- and post-vaccination sera from children vaccinated with the AMA1 vaccine and from a control group that received a rabies vaccine were tested for AMA1-specific immunoglobulin G (IgG) subclasses (IgG1, IgG2, IgG3, and IgG4) and for antibody avidity., Methods: Samples from a previously completed Phase 2 AMA1 vaccine trial in children residing in Mali, West Africa were used to determine AMA1-specific IgG subclass antibody titers and avidity by ELISA. Cox proportional hazards models were used to assess correlation between IgG subclass antibody titers and risk of time to first or only clinical malaria episode and risk of multiple episodes. Asexual P. falciparum parasite density measured for each child as area under the curve were used to assess correlation between IgG subclass antibody titers and parasite burden., Results: AMA1 vaccination did not elicit a change in antibody avidity; however, AMA1 vaccinees had a robust IgG subclass response that persisted over the malaria transmission season. AMA1-specific IgG subclass responses were not associated with decreased risk of subsequent clinical malaria. For the AMA1 vaccine group, IgG3 levels at study day 90 correlated with high parasite burden during days 90-240. In the control group, AMA1-specific IgG subclass rise and persistence over the malaria season was modest and correlated with age. In the control group, titers of several IgG subclasses at days 90 and 240 correlated with parasite burden over the first 90 study days, and IgG3 at day 240 correlated with parasite burden during days 90-240., Conclusions: Neither IgG subclass nor avidity was associated with the modest, strain-specific efficacy elicited by this blood stage malaria vaccine. Although a correlate of protection was not identified, correlations between subclass titers and age, and correlations between IgG subclass titers and parasite burden, defined by area under the curve parasitaemia levels, were observed, which expand knowledge about IgG subclass responses. IgG3, known to have the shortest half-life of the IgG subclasses, might be the most temporally relevant indicator of ongoing malaria exposure when examining antibody responses to AMA1.

Goal: The aim of this study was to compare the maternal-fetal prognosis of pregnancies at 40 years of age and above with that of pregnancies obtained before 40 years of age in the obstetric gynecology department of the reference health center of commune II of Bamako district., Materials and Methods: This was a prospective cohort study that was conducted at the maternity ward of Reference Health Center of Commune II of Bamako district from 1st January to 31 December 2012. Were included in our study as patients exposed, all the pregnant women of 40 years and over and as unexposed patients, pregnant women aged 20-39 who gave birth in our service. Teenage pregnancies were not included in this study. The statistical tests used were Pearson's Khi2 and Fisher's test with a significance level of 5%., Results: The frequency of pregnancy among women aged 40 and over was 1.68%. These were large multiparas unschooled patients in 60% of cases, with hypertension in 6.7% of cases. Pregnancy in her patients was associated with a high rate of caesarean section in 16.7% of cases, term overrun in 6.7% of cases, seat presentation in 6.7% of cases, macrosomia in 6.7% of cases and fetal malformation in 1.7% of cases., Conclusion: Slight account of its many maternal-fetal complications, pregnancies in women 40 years and older deserve special attention., (Le comitée de rédaction se réserve le droit de revoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de sonserver un examplaire du manuscrit, des figures et des tableaux.)

Purpose: Delays to access to radiotherapy are long in our context. The purpose of this study was to analyze the effect of neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancers., Patients and Methods: We conducted a retrospective study from April 2014 to April 2016 at the radiotherapy center of "Hopital du Mali" in Bamako, Mali. Patients were allocated according to age, histological type, tumor size and the 2002 classification of the FIGO. Experimental protocol was the administration of a neoadjuvante chemotherapy with association of Paclitaxel 175mg/m 2 + Carboplatine AUC 5 every 3 weeks and radiothérapy cure with avec linac 6 MV at 70 Gy due to 5 sessions of 2 Gy per week associated with a concomitant chemotherapy with cisplatin at 40 mg/m2/week. The clinical response was assessed at the end of neoadjuvant chemotherapy and of concomitant chemoradiotherapy., Results: Thirty patients were included in the study. The mean age was 53.63 ± 8.9 years. The mean size of the tumor was 5.17 cm (2 to 7 cm). According to the 2002 classification of the FIGO stages IIB were 33% (n = 10); IIIB were 57% (n = 17) and IVA were 10% (n = 3). Clinical evaluation at the end of neoadjuvant chemotherapy found: complete response 17 % (n = 5), partial response 10% (n = 3) and stable disease 73 % (n = 22). Evaluation at the end of the concomitant chemoradiotherapy had found the complete response in 90% (n = 27) and stable disease in 10% (n = 3)., Conclusion: Neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancer allows stabilization of the tumor and improves local control. Due to long delays to access to radiotherapy treatment in our context; neoadjuvant chemotherapy is an alternative to stabilize the disease and prevent distant metastasis from locally advanced cervical cancers., (Le comitée de rédaction se réserve le droit de revoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de sonserver un examplaire du manuscrit, des figures et des tableaux.)

Aim: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a hepatic secretory protein which promotes the degradation of low-density lipoprotein receptors leading to reduced hepatic uptake of plasma cholesterol. Non-synonymous single-nucleotide polymorphisms in its gene have been linked to hypo- or hyper- cholesterolemia, depending on whether they decrease or increase PCSK9 activity, respectively. Since the proliferation and the infectivity of Plasmodium spp. partially depend on cholesterol from the host, we hypothesize that these PCSK9 genetic polymorphisms could influence the course of malaria infection in individuals who carry them. Here we examined the frequency distribution of one dominant (C679X) and two recessive (A443T, I474V) hypocholesterolemic polymorphisms as well as that of one recessive hypercholesterolemic polymorphism (E670G) among healthy and malaria-infected Malian children., Methods: Dried blood spots were collected in Bandiagara, Mali, from 752 age, residence and ethnicity-matched children: 253 healthy controls, 246 uncomplicated malaria patients and 253 severe malaria patients. Their genomic DNA was extracted and genotyped for the above PCSK9 polymorphisms using Taqman assays. Associations of genotype distributions and allele frequencies with malaria were evaluated., Results: The minor allele frequency of the A443T, I474V, E670G, and C679X polymorphisms in the study population sample was 0.12, 0.20, 0.26, and 0.02, respectively. For each polymorphism, the genotype distribution among the three health conditions was statistically insignificant, but for the hypercholesterolemic E670G polymorphism, a trend towards association of the minor allele with malaria severity was observed (P = 0.035). The association proved to be stronger when allele frequencies between healthy controls and severe malaria cases were compared (Odd Ratio: 1.34; 95% Confidence Intervals: 1.04-1.83); P = 0.031)., Conclusions: Carriers of the minor allele of the E670G PCSK9 polymorphism might be more susceptible to severe malaria. Further investigation of the cholesterol regulating function of PCSK9 in the pathophysiology of malaria is needed.

Polyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP) Malian children, aged 4-8 years, are protected from malaria compared to matched schistosomiasis-negative (SN) children. The effect of concomitant schistosomiasis upon acquisition of T cell memory is unknown. We examined antigen-specific T cell frequencies in 48 Malian children aged 4-14 to a pool of malaria blood stage antigens, and a pool of schistosomal antigens, at a time point during a malaria episode and at a convalescent time point ~6 months later, following cessation of malaria transmission. CD4 + T cell-derived memory responses, defined as one or more significant cytokine (IFN-γ, TNF-α, IL-2, and/or IL-17 A ) responses, was measured to schistoma antigens in 18/23 SP children at one or both time points, compared to 4/23 SN children ( P  < 0.0001). At the time of malaria infection, 12/24 SN children and 15/23 SP children ( P  = 0.29) stimulated with malaria antigens demonstrated memory recall as defined by CD4-derived cytokine production. This compares to 7/23 SN children and 16/23 SP children ( P  = 0.009) at the convalescent timepoint. 46.2% of cytokine-producing CD4 + T cells expressed a single cytokine after stimulation with malaria antigen during the malaria episode. This fell to 40.9% at follow-up with a compensatory rise of multifunctional cytokine secretion over time, a phenomenon consistent with memory maturation. The majority (53.2-59.5%) of responses derived from CD45RA - CD62L - effector memory T cells with little variation in the phenotype depending upon the time point or the study cohort. We conclude that detectable T cell memory responses can be measured against both malaria and schistosoma antigens and that the presence of Schistosoma haematobium may be associated with long-term maintenance of T memory to malaria.

In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009-2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2-3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 2009-2014, cluster locations did not vary from year to year. Asymptomatic and gametocyte carriage were persistent, even during low transmission periods. For high transmission periods, the ratio of asymptomatic to clinical cases was approximately 0.5, but was five times higher during low transmission periods. Clinical episodes at previous high transmission periods were a protective factor for asymptomatic carriage, but carrying parasites without symptoms at a previous high transmission period was a risk factor for asymptomatic carriage. Stable malaria transmission was associated with sustained asymptomatic carriage during dry seasons. Control strategies should target persistent low-level parasitemia clusters to interrupt transmission.

Background: Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40-60 var gene complement for individual infections has been notoriously difficult, impeding molecular epidemiological studies and the assessment of particular var elements as subunit vaccine candidates., Methods: We developed and validated a novel algorithm, Exon-Targeted Hybrid Assembly (ETHA), to perform targeted assembly of var gene sequences, based on a combination of Pacific Biosciences and Illumina data., Results: Using ETHA, we characterized the repertoire of var genes in 12 samples from uncomplicated malaria infections in children from a single Malian village and showed them to be as genetically diverse as vars from isolates from around the globe. The gene var2csa, a member of the var family associated with placental malaria pathogenesis, was present in each genome, as were vars previously associated with severe malaria., Conclusion: ETHA, a tool to discover novel var sequences from clinical samples, will aid the understanding of malaria pathogenesis and inform the design of malaria vaccines based on PfEMP1. ETHA is available at: https://sourceforge.net/projects/etha/ .

The blood-stage malaria vaccine FMP2.1/AS02A, comprised of recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) and the adjuvant system AS02A, had strain-specific efficacy against clinical malaria caused by P. falciparum with the vaccine strain 3D7 AMA1 sequence. To evaluate a potential correlate of protection, we measured the ability of participant sera to inhibit growth of 3D7 and FVO strains in vitro using high-throughput growth inhibition assay (GIA) testing. Sera from 400 children randomized to receive either malaria vaccine or a control rabies vaccine were assessed at baseline and over two annual malaria transmission seasons after immunization. Baseline GIA against vaccine strain 3D7 and FVO strain was similar in both groups, but more children in the malaria vaccine group than in the control group had 3D7 and FVO GIA activity ≥15% 30 days after the last vaccination (day 90) (49% vs. 16%, p<0.0001; and 71.8% vs. 60.4%, p = 0.02). From baseline to day 90, 3D7 GIA in the vaccine group was 7.4 times the mean increase in the control group (p<0.0001). In AMA1 vaccinees, 3D7 GIA activity subsequently returned to baseline one year after vaccination (day 364) and did not correlate with efficacy in the extended efficacy time period to day 730. In Cox proportional hazards regression models with time-varying covariates, there was a slight suggestion of an association between 3D7 GIA activity and increased risk of clinical malaria between day 90 and day 240. We conclude that vaccination with this AMA1-based malaria vaccine increased inhibition of parasite growth, but this increase was not associated with allele-specific efficacy in the first malaria season. These results provide a framework for testing functional immune correlates of protection against clinical malaria in field trials, and will help to guide similar analyses for next-generation malaria vaccines. Clinical trials registry: This clinical trial was registered on clinicaltrials.gov, registry number NCT00460525.