Consequences of cathepsin C inactivation for membrane exposure of proteinase 3, the target antigen in autoimmune vasculitis.

Membrane-bound proteinase 3 (PR3m) is the main target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA) in granulomatosis with polyangiitis, a systemic small-vessel vasculitis. Binding of ANCA to PR3m triggers neutrophil activation with the secretion of enzymatically active PR3 and related neutrophil serine proteases, thereby contributing to vascular damage. PR3 and related proteases are activated from pro-forms by the lysosomal cysteine protease cathepsin C (CatC) during neutrophil maturation. We hypothesized that pharmacological inhibition of CatC provides an effective measure to reduce PR3m and therefore has implications as a novel therapeutic approach in granulomatosis with polyangiitis. We first studied neutrophilic PR3 from 24 patients with Papillon-Lefèvre syndrome (PLS), a genetic form of CatC deficiency. PLS neutrophil lysates showed a largely reduced but still detectable (0.5-4%) PR3 activity when compared with healthy control cells. Despite extremely low levels of cellular PR3, the amount of constitutive PR3m expressed on the surface of quiescent neutrophils and the typical bimodal membrane distribution pattern were similar to what was observed in healthy neutrophils. However, following cell activation, there was no significant increase in the total amount of PR3m on PLS neutrophils, whereas the total amount of PR3m on healthy neutrophils was significantly increased. We then explored the effect of pharmacological CatC inhibition on PR3 stability in normal neutrophils using a potent cell-permeable CatC inhibitor and a CD34+ hematopoietic stem cell model. Human CD34+ hematopoietic stem cells were treated with the inhibitor during neutrophil differentiation over 10 days. We observed strong reductions in PR3m, cellular PR3 protein, and proteolytic PR3 activity, whereas neutrophil differentiation was not compromised.

Knowledge, Attitudes and Behaviors of Clients Regarding Cervical Cancer Screening at Gynecology Consultations of the University Hospital of Cocody.

Background: Cervical cancer (CC) is a public health problem because of its increasing prevalence and mortality in low- and middle-income countries. Objective: To study knowledge, attitudes, and practices about CC and screening among women in a referral hospital in Côte d'Ivoire, a sub-Saharan African country. Materials and Methods: A cross-sectional study, from September 1, 2020 to March 1, 2021, in the obstetric gynecology consultation unit of the University Hospital of Cocody. It included patients who gave informed consent. Data were collected using a questionnaire. Data analysis was performed using Epi data 3.1 software (CDC Atlanta-USA). Results: 1200 women were included (47.2%) with a mean age of 32 years. General knowledge ranged from 6.2 to 32.7% and main risk factors were advanced age (75.2%), HIV infection (60.3%), early marriage (38.2%), and multiple sexual partners (25.8%). 975 women were able to provide a response (81.3%). 85.2% of women identified signs and symptoms: vaginal bleeding (83.6%), intermenstrual bleeding (65.1%), and foul-smelling discharge (11.9%). The level of knowledge of screening was 79% for PAP smear, 72.6% for VIA and 14.2% for LBC. A positive attitude was observed since 87.8% declared they wanted to perform screening. A significant practice (60.4%) was demonstrated, and the screening tests used were visual inspection with acetic acid (52.6%), Pap smear (39.8%) and liquid-based cytology (7.6%). Conclusion: We revealed a good knowledge of reality of CC, but effective information, education and communication strategies are needed to improve the level of awareness about risk factors, symptoms and preventive methods.

[Pulmonary events induced by non-steroidal anti-inflammatory drugs in patients with sickle cell disease]. / Manifestations respiratoires induites par les anti-inflammatoires non stéroïdiens chez le drépanocytaire.

Painful sickle cell crises are among the principal manifestations of sickle cell disease. Their treatment routinely requires the use of non-steroidal anti-inflammatory drugs (NSAIDS). These drugs also, however, inhibit the cyclooxygenase cycle in arachidonic acid metabolism, promoting the synthesis of leukotrienes, which have bronchoconstrictive effects. This study took place from March through August, 2007, and included 100 patients of both sexes, aged 2 to 59 years, with any sickle cell phenotype (SS, SC, AS, SFA2, or SAFA2) and treated by NSAIDs in the Immunology and Haematology department of the University Hospital of Cocody. We analysed the characteristics of the respiratory events induced by taking NSAIDs to identify potential risk factors for their occurrence. We found that 5% of these patients presented respiratory symptoms linked to NSAIDs. These appeared within 30 minutes of drug intake for 80%; in 60% of these cases, only corticosteroid and antihistamine treatment resolved these symptoms. The occurrence of respiratory events did not differ by sex; however, younger subjects were more exposed to these respiratory events. All patients with family or individual history of atopy-like hypersensitivity type I events presented these respiratory symptoms when taking NSAIDS for sickle-cell crises.

Human proteinase 3 resistance to inhibition extends to alpha-2 macroglobulin.

Polymorphonuclear neutrophils contain at least four serine endopeptidases, namely neutrophil elastase (NE), proteinase 3 (PR3), cathepsin G (CatG), and NSP4, which contribute to the regulation of infection and of inflammatory processes. In physiological conditions, endogenous inhibitors including α2-macroglobulin (α2-M), serpins [α1-proteinase inhibitor (α1-PI)], monocyte neutrophil elastase inhibitor (MNEI), α1-antichymotrypsin, and locally produced chelonianins (elafin, SLPI) control excessive proteolytic activity of neutrophilic serine proteinases. In contrast to human NE (hNE), hPR3 is weakly inhibited by α1-PI and MNEI but not by SLPI. α2-M is a large spectrum inhibitor that traps a variety of proteinases in response to cleavage(s) in its bait region. We report here that α2-M was more rapidly processed by hNE than hPR3 or hCatG. This was confirmed by the observation that the association between α2-M and hPR3 is governed by a kass in the ≤ 105  m-1 ·s-1 range. Since α2-M-trapped proteinases retain peptidase activity, we first predicted the putative cleavage sites within the α2-M bait region (residues 690-728) using kinetic and molecular modeling approaches. We then identified by mass spectrum analysis the cleavage sites of hPR3 in a synthetic peptide spanning the 39-residue bait region of α2-M (39pep-α2-M). Since the 39pep-α2-M peptide and the corresponding bait area in the whole protein do not contain sequences with a high probability of specific cleavage by hPR3 and were indeed only slowly cleaved by hPR3, it can be concluded that α2-M is a poor inhibitor of hPR3. The resistance of hPR3 to inhibition by endogenous inhibitors explains at least in part its role in tissue injury during chronic inflammatory diseases and its well-recognized function of major target autoantigen in granulomatosis with polyangiitis.

Lassa fever clinical course and setting a standard of care for future randomized trials: A protocol for a cohort study of Lassa-infected patients in Nigeria (LASCOPE).

BACKGROUND: Lassa Fever (LF), is a severe viral disease prevalent in Western Africa. It is classified as a priority disease by the World Health Organization (WHO). Ribavirin is the recommended therapy despite weak evidence of its efficacy. Promising therapeutic agents are becoming available for evaluation in human. Before launching therapeutic trials, we need data on the evolution of the disease under the best possible conditions of care. METHODS: We have initiated a prospective study in Nigeria to better understand the clinical course and prognostic factors of LF while implementing high quality standardized care. Inclusion criteria are: suspected or confirmed LF and informed consent. Participants are followed 60 days from admission and receive free of charge standardized supportive care and biological monitoring, as well as intravenous ribavirin for those with confirmed LF. Data are collected using standardized case report forms (CRF). Primary and secondary outcomes are fatality and severe morbidity, with special focus on acute kidney dysfunction and pregnancy complications. Factors associated with outcomes will be investigated. RESULTS: The cohort is planned for 3 years. Inclusions started in April 2018 at the Federal Medical Center Owo in Ondo State. A second site will open in Nigeria in 2020 and discussions are underway to open a site in Benin. 150 to 200 new participants are expected per year. CONCLUSIONS: This cohort will: provide evidence to standardize LF case management; provide key inputs to design future clinical trials of novel therapeutics; and establish clinical research teams capable of conducting such trials in LF-endemic areas. STUDY REGISTRATION: The LASCOPE study was registered on ClinicalTrial.gov (NCT03655561).

Oral epidemiological profile of patients attending public oral health services in Haut Sassandra region, in Côte d'Ivoire.

The objective of this cross-sectional study was to determine the type of care that can be achieved and the epidemiological profile of patients attending the 3 public dental practices in the Haut-Sassandra region, in Côte d'Ivoire. The data collection concerned socio-demographic characteristics, reason for consultation, oral hygiene, dental condition, malocclusions and the availability of equipment for the performance of procedures. The 400 patients observed (51.5% male) were aged 16.0 to 86.0 years (mean=35.5 years; SD=13.1 years). The main reasons for consultation were pain (91.5%) and aesthetics (23.5%). Oral hygiene was insufficient for 36.8% of subjects. Oral conditions were malocclusions (12.8%), caries (98.7%) and edentulous (65.7%) with only 11.8% with prosthesis. The average DMFT index was 9.3. Only extractions and resin attached prostheses were possible in all 3 health facilities. Preventive dentistry (sealent, fluoridation), dentofacial orthopedics and implantology were not available in any dental practice. The most frequently performed acts were extractions (74.5%). The results of this study highlight the need for oral health planning with service equipment and awareness among populations who shouldn't wait until they are in pain to consult.

[External evaluation of the quality of CD4 T cells enumeration in the laboratory of immunology and hematology at the Cocody University Hospital Center]. / Evaluation externe de la qualité de la numération des lymphocytes T-CD4 au laboratoire d'immunologie et hématologie du CHU de Cocody.

INTRODUCTION: The rate of T lymphocytes-CD4 (TLR4) is a crucial parameter for therapeutic decision and follow-up in patients with Human Immunodeficiency Virus (HIV) infection. This must be determined in a reliable and accurate way. The laboratory of immunology and hematology at the Cocody University Hospital Center has participated in the External Quality Assessment program (EQAP) for TLR4 enumeration provided by QASI (Quality Assessment and Standardization for Immunological Measures Relevant to HIV/AIDS) in order to deliver quality results. This study aims to assess laboratory performance in TLR4 enumeration. METHODS: We conducted a retrospective study to evaluate the laboratory performance reports from EQAP. Performance indicators such as SDI (Standard Deviation Index) and CV (coefficient of variation) were evaluated. RESULTS: Program participation rate was 83.33%. Performance indicators were satisfactory. The majority of SDI were included in the confidence interval [-2; +2]. The CV of samples with normal CD4 values were within the standards. Compliance rate of CD4 results was 89.58% and 91.87% for the absolute and the relative performance respectively. The CV of samples with low CD4 rates were beyond the standards (>15%). CONCLUSION: EQAP is an indispensable tool enabling laboratory to monitor the quality of its analyses. However, corrective measures should be strengthened during the follow-up period to sustain and improve the quality of the analyses.

[Gestational diabetes revealed by inaugural diabetic ketoacidosis: about a case]. / Diabète gestationnel révélé par une acidocétose diabétique inaugural: à propos de un cas.

Ketoacidosis complicating gestational diabetes is rare and responsible for severe maternal-fetal mortality. It is an acute metabolic emergency whose management is multidisciplinary. Early diagnosis and treatment affect the vital prognosis of both the mother and the fetus. We report the case of a 27-year old pregnant woman at term, with a family history of diabetes, admitted to the emergency obstetric care with alertness problems associated with dyspnoea. The diagnosis of inaugural ketoacidosis decompensated due to severe malaria associated with gestational diabetes was retained on the basis of patient's medical history, of clinical examination and paraclinical assessment. The patient received insulin therapy, rehydration therapy, correction of electrolyte imbalance as well as antimalarial treatment. She underwent emergency cesarean section under general anesthesia and a dead-born macrosome macerated male fetus was extracted. Patient's evolution was favorable, with return of consciousness and standardization of biological parameters.

[Malaria serology test: what contribution does it make in an endemic country such as Ivory Coast?] / Sérologie palustre: quel apport dans un pays d'endémie palustre comme la Côte d'Ivoire?

INTRODUCTION: Malaria serology test seems to have attracted very little interest in endemic countries such as Ivory Coast. However, this examination has been regularly performed in the parasitology laboratory at the Training and Research Unit of Medical Sciences in Abidjan. Our study aimed to highlight the contribution of malaria serology test in our endemic country context. METHODS: We conducted a retrospective study of malaria serology test using Falciparum-Spot IF (bioMerieux) kit for the detection of IgG antiplasmodial antibodies. It included all malaria serology tests performed from January 2007 to February 2011 and whose results were available in the registry. RESULTS: In total, 136 patients were selected. The average age of patients was 36,3 years, ranging from 1 to 81 years, and sex ratio was 0,97. Indications for malaria serology test were varied and dominated by splenomegaly (49.3%), cytopenias (14.7%), indeterminate fever (13.2%). Almost all of the patients (98.5%) had antiplasmodial antibodies with high medium titer of 1057,35IU/ml. There was no link between age and Ab titer, which was higher in cytopenias, prolonged fevers and the splenomegaly. CONCLUSION: Malaria serology test seems to have attracted very little interest in routine clinical practice provided in our endemic area because, whatever the reason of the prescription, titers were high.

Immunity Status of Blood Donors Regarding Toxoplasma gondii Infection in a Low-Income District of Abidjan, Côte d'Ivoire, West Africa.

Background. Toxoplasmosis is a widespread cosmopolitan anthropozoonosis, which affects more than a third of the world population. Except the modes of transmission well known, Toxoplasma gondii can be transmitted during transplantation or blood transfusion. The aim of this study is to determine the prevalence of IgG and IgM Toxoplasma gondii and to estimate the potential risk by blood products. Methods. This is a cross-sectional study on the research for Toxoplasma gondii antibodies (IgG and IgM) blood donors performed by ELISA. Results. An overall seroprevalence of Toxoplasma gondii among blood donors recruited was 67.92% (n = 72). Among these, 68 have Toxoplasma gondii IgG (64.15%), 12 Toxoplasma gondii IgM (11.32%), and 4 (3.77%) both. The risk varies between 8 for 100000 and 172 for 100000 donations. Conclusion. The need to strengthen security measures for people multitransfused, immunocompromised, and pregnant women to reduce the transmission of toxoplasmosis is important.

Lability of IgE Levels Early in Life.

We report a case of a very fast and intriguing decrease in IgE concentrations after exclusion from the diet of any CM lysate in an unusual clinical presentation of cow's milk allergy in an infant. Analysis of IgE kinetics after allergen elimination suggests rapid cessation of IgE biosynthesis and a short IgE half-life.

Sérologie palustre: quel apport dans un pays d'endémie palustre comme la Côte d'Ivoire?

Introduction: la sérologie palustre semble avoir peu d'intérêt dans les pays d'endémie comme la Côte d'Ivoire. Cependant cet examen a été régulièrement réalisé au laboratoire de Parasitologie de l'Unité de Formation et de Recherche Sciences Médicales d'Abidjan. Le but de notre étude était d'apprécier l'apport de la sérologie palustre dans notre contexte de pays endémique.Méthodes: nous avons réalisé une étude rétrospective portant sur la sérologie palustre qui a utilisé le kit Falciparum spot-IF de Biomérieux à la recherche d'anticorps antiplasmodiaux d'isotype IgG. Elle a concerné les sérologies réalisées de janvier 2007 à février 2011 et dont les résultats étaient disponibles dans le registre.Résultats: au total, 136 patients ont été sélectionnés. L'âge moyen était de 36,3 ans avec des extrêmes de 1 an et 81 ans et un sex-ratio de 0,97. Les indications de sérologie palustre étaient variées, dominées par la splénomégalie (49,3%), les cytopénies (14,7%), la fièvre d'origine indéterminée (13,2%). La quasi-totalité des patients (98,5%) avaient des anticorps antiplasmodiaux avec un titre moyen élevé à 1057,35UI/ml. Il n'existait pas de lien entre l'âge et le titre d'Ac qui était plus élevé pour les cytopénies, les fièvres prolongées et la splénomégalie.Conclusion: la sérologie palustre a peu d'intérêt dans notre pratique courante en zone d'endémie car quelque soit le motif de la prescription, les titres étaient élevés