Incidence of adverse reactions caused by first-line anti-tuberculosis drugs and treatment outcome of pulmonary tuberculosis patients in Morocco.

PURPOSE: The treatment of tuberculosis is associated with a high incidence of adverse reactions with different degrees of severity. The aim of this study was to determine the incidence of adverse reactions caused by first-line anti-tuberculosis drugs and to evaluate the treatment outcome of TB patients in a large region of Morocco. METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established for data collection from clinical charts of TB patients. The study was carried out in all the 18 centers located in the Rabat-Salé-Kénitra region of Morocco where tuberculosis is treated. Adverse reactions are evaluated from the start of TB treatment until its end by a specialist clinician. The treatment outcomes are evaluated, and the definitions and classifications of these outcomes are defined according to World Health Organization guidelines. RESULTS: Among a total number of 2532 patients treated for TB, the average age is 37.3 ± 16.4 years, 10.0% of patients produced adverse reactions. 7.4% of adverse reactions are gastrointestinal, 3.7% are cutaneous, 2.0% are hepatic, 1.14% are articular, 1.07% are immunoallergic, 0.7% are neuropsychiatric, and 0.1% are ocular. The treatment outcome of TB patients is 79.1% rate for successful treatment and 15.6% for unsuccessful treatment. CONCLUSION: Adverse reactions caused by anti-TB drugs are frequent among patients with TB. These ADRs must be followed up by a closer monitoring during anti-TB treatment period. Treatment success outcome in our study is slightly lower than the success rate target of WHO of at least 85%.

Treatment outcomes of drug resistant tuberculosis patients in Morocco: multi-centric prospective study.

BACKGROUND: Drug resistant tuberculosis is a major public health problem in Morocco and worldwide. Treatment outcome of drug resistant tuberculosis is poor and requires a long period of treatment with many toxic and expensive antituberculosis drugs. The aim of this study is to evaluate treatment outcomes of drug resistant tuberculosis and to determine predictors of poor treatment outcomes in a large region of Morocco. METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established to collect data from clinical charts of patients with confirmed resistant TB. The study was carried out in all the 11 centers located in the Rabat-Salé-Kénitra region of Morocco where drug resistant tuberculosis is treated. Treatment outcomes were reported and the definitions and classifications of these outcomes were defined according to the WHO guidelines. Univariate and multivariate logistic regression were conducted to determine factors associated with poor drug resistant tuberculosis treatment outcomes in Morocco. RESULTS: In our study, 101 patients were treated for drug resistant tuberculosis between January 01, 2014 and January 01, 2016. Patients' age ranged from 9.5 to70 years; 72patients (71.3%) were male and 80 patients (79.2%) were living in urban areas. Thirty two patients were smokers, 74 patients had multidrug-resistant tuberculosis, 25 patients had rifampicin resistance and 2 patients had isoniazid resistance. Treatment outcomes of tuberculosis patients were as follows: 45 patients were cured (44.5%), 9 completed treatment (8.9%), 5 patients died before completing the treatment, 35 patients were lost to follow up (34.6%) and 7 patients had treatment failure. In the multivariate analysis, being a smoker is an independent risk factor for poor treatment outcomes, (p-value = 0.015, OR = 4.355, IC [1.327-14.292]). CONCLUSION: Treatment success outcomes occurred in more than half of the cases, which is lower than the World Health Organization target of at least a 75% success rate. A significant number of patients abandoned their treatment before its completion. These dropouts are a serious public health hazard that needs to be addressed urgently.

Molecular characterization of mutations associated with resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients from high prevalence tuberculosis city in Morocco.

BACKGROUND: The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised public health concern for global TB control. Although multi drug-resistant tuberculosis (MDR- TB) prevalence and associated genetic mutations in Morocco are well documented, scarce information on XDR TB is available. Hence, the evaluation of pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drugs, is of great value for better management of M/XDR TB in Morocco. OBJECTIVES: To evaluate pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drug resistance, in 703 clinical isolates from TB patients recruited in Casablanca, and to assess the usefulness of molecular tools in clinical laboratories for better management of M/XDR TB in Morocco. METHODS: Drug susceptibility testing (DST) was performed by the proportional method for first line drugs, and then the selected MDR isolates were tested for second line drugs (Ofloxacin, Kanamycin, Amikacin and Capreomycin). Along with DST, all samples were subjected to rpoB, katG and p-inhA mutation analysis by PCR and DNA sequencing. MDR isolates as well as 30 pan-susceptible strains were subjected to PCR and DNA sequencing of gyrA, gyrB, rrs, tlyA genes and eis promoter, associated with resistance to fluoroquinolones and injectable drugs. RESULTS: Among the 703 analysed strains, 12.8% were MDR; Ser531Leu and Ser315Thr being the most common recorded mutations within rpoB and katG genes associated with RIF and INH resistance respectively. Drug susceptibility testing for second line drugs showed that among the 90 MDR strains, 22.2% (20/90) were resistant to OFX, 2.22% (2/90) to KAN, 3.33% (3/90) to AMK and 1.11% (1/90) to CAP. Genotypic analysis revealed that 19 MDR strains harbored mutations in the gyrA gene; the most recorded mutation being Asp91Ala accounting for 47.6% (10/21), and 2 isolates harbored mutations in the promoter region of eis gene. No mutation was found in gyrB, rrs and tlyA genes. Moreover, none of the pan-susceptible isolates displayed mutations in targeted genes. CONCLUSION: Most of mutations associated with SLD resistance occurred in gyrA gene (codons 90-94) and eis promoter region. These findings highlight the impact of mutations in gyrA on the development of fluroquinolones resistance and provide the first estimates of the proportion of pre-XDR-TB among MDR-TB cases in Morocco.

New variant identified in major susceptibility locus to tuberculosis on chromosomal region 8q12-q13 in Moroccan population: a case control study.

BACKGROUND: Tuberculosis (TB) remains a global health problem. Several studies have implicated genetic host factors in predisposing populations to TB disease. In this study, we have selected NSMAF (Neutral Sphingomyelinase Activation Associated Factor) as a candidate gene to evaluate its level of association with TB disease in a Moroccan population for two reasons: first, this gene is located in a major susceptibility locus on chromosomal region 8q12-q13 in the Moroccan population, closely linked to the CYP7A1 gene, which was previously shown to be associated with TB disease; second, NSMAF has an important role in immune system function. METHODS: We conducted a case-control study including 269 genomic DNA samples extracted from pulmonary TB (PTB) patients and healthy controls (HC). We genotyped three selected SNPs (rs2228505, rs36067275 and rs10505004) using TaqMan® allelic discrimination assays. RESULTS: Only the rs1050504 C > T genotype was observed to be significantly associated with an increased risk for developing pulmonary TB (41.8% vs 27%, OR 1.95, 95% CI 1.16-3.27; p = 0.01). In contrast, the TT genotype was significantly associated with resistance to PTB (4.1% vs 15.6%, OR 0.23, 95% CI 0.08-0.63; p = 0.002). CONCLUSION: Our findings suggest that genetic variations in the NSMAF gene could modulate the risk of PTB development in a Moroccan population. Further functional studies are needed to confirm these findings.

[Endobronchial aspergilloma revealing a bronchial carcinoma]. / Aspergillome endo-bronchique révélant un carcinome bronchique.

Endobronchial aspergillosis is a rare presentation of pulmonary aspergillosis in immunocompetent patients; this raises questions about structural changes inducing airflow stasis in order to colonize the bronchial lumen. We present the case of a patient diagnosed with endobronchial aspergilloma covering a bronchial adenocarcinoma.

Reference Values for Spirometry in Moroccan Adults.

INTRODUCTION: This novel study aimed to establish spirometric reference values and prediction equations based on a sample of the adult Moroccan population, an endeavor that has not been attempted previously. METHODS: In this cross-sectional study involving healthy Moroccan adults, data was collected through a mobile spirometry setup. RESULTS: Our sample comprised 841 healthy adults (384 men and 457 women) aged 18-86 years who underwent spirometry. For both sexes, the Global Lung Function Initiative 2012 equations for Caucasians corresponded the best to the studied sample but were not perfectly compatible. CONCLUSION: The spirometric prediction equations established in this study for Moroccan adults aged 18-86 years best represent the Moroccan population. More extensive future studies are needed to enrich the database of reference values and prediction equations derived from our research.

Recurrence of Cervical Squamous Cell Carcinoma After More Than 4 Years in the Lung: A Rare Case Report.

Cervical squamous cell carcinoma (CSCC) is a common gynecological malignancy, typically affecting women of reproductive age. Although the occurrence of late metastatic recurrence in the lung is relatively rare, we present the case of a 52-year-old woman, previously diagnosed and treated for CSCC. After 4 years of disease-free intervals, she presented with respiratory symptoms, including cough, dyspnea, and hemoptysis, with marked asthenia. A computed tomography (CT) scan of the chest revealed a lung mass. Histopathological examination of the lung biopsy confirmed the recurrence of CSCC, specifically in the lung. Immunohistochemistry further supported the origin of the tumor as cervical. The management of such cases necessitates a multidisciplinary approach, considering treatment options such as surgery and chemoradiation. Long-term follow-up and surveillance are vital for the early detection of late recurrences, as they can present several years after the initial diagnosis. This case report highlights the importance of recognizing and appropriately managing cases of late metastatic recurrence of CSCC in the lung. Further studies are needed to deepen our understanding of the underlying mechanisms, refine diagnostic approaches, and optimize treatment strategies for such rare occurrences.

Anaphylactic Shock After First-Line Treatment With Antituberculosis Drugs in a Patient With Lupus.

Tuberculosis (TB) is still a major public health concern in Morocco. Although first-line antituberculosis drugs (ATD) are generally considered safe and effective, serious adverse events can occur. In this case report, we describe a female with pulmonary TB who experienced anaphylaxis induced by rifampicin (RFP) and pyrazinamide (PZA) during ATD therapy. Anaphylactic reactions to first-line ATD can occur and may lead to treatment discontinuation and challenges in finding effective alternative treatment options. Healthcare professionals should be aware of the potential of anaphylaxis with the use of these drugs, especially in patients with a history of lupus. Further research is needed to better understand the mechanisms underlying anaphylaxis and develop effective preventive and management strategies. A young female patient with a history of lupus and splenectomy presented with respiratory symptoms and deterioration of general condition. She was diagnosed with pulmonary tuberculosis and received first-line ATD, which caused complications including liver dysfunction and anaphylactic shock. Despite these challenges, the anaphylactic shock was successfully managed; she was put on a combination of levofloxacin, kanamycin, and ethambutol (ETB), as well as a desensitization protocol for isoniazid (INH); the patient was cured.

On the Implementation of a Post-Pandemic Deep Learning Algorithm Based on a Hybrid CT-Scan/X-ray Images Classification Applied to Pneumonia Categories.

The identification and characterization of lung diseases is one of the most interesting research topics in recent years. They require accurate and rapid diagnosis. Although lung imaging techniques have many advantages for disease diagnosis, the interpretation of medial lung images has always been a major problem for physicians and radiologists due to diagnostic errors. This has encouraged the use of modern artificial intelligence techniques such as deep learning. In this paper, a deep learning architecture based on EfficientNetB7, known as the most advanced architecture among convolutional networks, has been constructed for classification of medical X-ray and CT images of lungs into three classes namely: common pneumonia, coronavirus pneumonia and normal cases. In terms of accuracy, the proposed model is compared with recent pneumonia detection techniques. The results provided robust and consistent features to this system for pneumonia detection with predictive accuracy according to the three classes mentioned above for both imaging modalities: radiography at 99.81% and CT at 99.88%. This work implements an accurate computer-aided system for the analysis of radiographic and CT medical images. The results of the classification are promising and will certainly improve the diagnosis and decision making of lung diseases that keep appearing over time.

Functional characterization of small and large alveolar macrophages in sarcoidosis and idiopathic pulmonary fibrosis compared with non-fibrosis interstitial lung diseases.

BACKGROUND: Sarcoidosis is a granulomatous disease that mostly affects the lungs. Advanced tissue injury caused by this disease can progress to pulmonary fibrosis with similar characteristics shared with idiopathic pulmonary fibrosis (IPF). The initial presentations of both sarcoidosis and IPF may be shared with other interstitial lung diseases (ILDs). Two populations of macrophages have been described in the alveolar space: small alveolar macrophages (AMs) and large alveolar macrophages. Despite their protective function, these cells may also play a role in the initiation and maintenance of inflammation leading to fibrosis. OBJECTIVE: The aim of this study was the functional characterization of small and large AM subpopulations in sarcoidosis and IPF as a pathology with respectively mild and advanced tissue injury causing fibrosis, in comparison with non-fibrosis ILDs. METHODS: Activation and adhesion surface markers as well as functions of small and large AMs isolated from bronchoalveolar lavage (BAL) were assessed by Flow Cytometry within patients with confirmed sarcoidosis (n= 14), IPF (n= 6), and non-fibrosis ILDs (n= 9). RESULTS: Our results showed that small AMs are immunologically more active, which may be important for airway inflammation. They are also proportionally more abundant in IPF, and therefore they may be more involved in a fibrosis process associated with the down-regulation of HLA-DR, LeuCAM, and CD62L expression. In Sarcoidosis, the inflammatory process appears to be associated with up-regulation of CD38 expression and oxidative burst activity. CONCLUSION: A relevant potential of the activation and adhesion markers as well as oxidative burst activity expressed on small and large AMs, in the perspective of differential diagnosis of sarcoidosis and IPF.

Assessment of the Association of Chlamydia e pneumoniae Infection with Lung Cancer in a Moroccan Patients' Cohort.

BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) is a respiratory pathogen associated with chronic inflammatory and its detection in human lung cancer suggests its involvement in cancerogenesis. Our study aimed to evaluate the association between C. pneumoniae  infection and Lung Cancer disease in Moroccans patients and control cohorts, through a molecular investigation. METHODS: The study comprised 42 lung cancer patients and 43 healthy controls. All participants provided demographics, Clinical, and Toxic behaviors datas, and a peripheral blood sample for testing, a Nested Polymerase Chain Reaction (PCR) was performed for C. pneumoniae Deoxyribonucleic acid (DNA) detection. Statistical analysis was performed using IBM®SPSS®software. RESULTS: Positive Nested PCR results for cases and controls were respectively 33.3% and 4.7%, there by  significant difference between cases and controls   infection was identified (p <0.05). Data analysis also showed that tobacco could act synergically with C. pneumoniae infection as a risk factor of lung cancer. In fact a significant difference between patients and controls was shown for tobacco and alcohol use (p < 0.05). CONCLUSION: C. pneumoniae infection is potentially associated with primary Lung cancer in the Moroccan population and has combined effects with Tabaco consumption.

Macrophagic activation syndrome revealing disseminated multifocal tuberculosis: A case report of a rare clinical situation.

Introduction: Macrophage activation syndrome (MAS) is a rare but serious entity, sometimes triggered by an infectious agent, in particular by certain viruses or mycobacteria. Forms of tuberculosis complicated by MAS frequently occur in immunocompromised subjects. The disease is often disseminated, severe, and has a poor prognosis. Case presentation: We report a case of MAS complicating disseminated tuberculosis and revealing HIV in a previously healthy young patient. Discussion & conclusion: The management of macrophage activation syndrome related to tuberculosis is complex and not codified. On the one hand, the immunosuppressive treatment allows to slow down the macrophage activation syndrome and obtain a correction of cytopenia. On the other hand, there is a risk of aggravating tuberculosis by increasing the patient's immunodepression.

A Rare Case of Isolated Ovarian Tuberculosis Incidentally Found During In Vitro Fertilization Workup in a Young Woman With Primary Infertility.

Female genital tuberculosis (TB) is a common form of extrapulmonary TB (EPTB). It is a major cause of infertility in low-income countries, and in many cases, it is asymptomatic and typically not diagnosed until the patient seeks medical advice for infertility. The infection is usually secondary to primary pulmonary TB via hematogenous or lymphatic dissemination, but sexual transmission through genital TB of the partner is also possible. We describe a rare case of isolated ovarian TB as a fortuitous diagnosis during in vitro fertilization (IVF) workup in a 40-year-old woman with primary sterility and no specific symptoms. This case highlights the importance of screening for TB before an IVF procedure in women with infertility, especially in countries with a high prevalence of this disease.

Exceptional association of hepatic and pancreatic tuberculosis mimicking metastatic pancreatic neoplasia: A case report and review of the literature.

Introduction: Despite the high prevalence of tuberculosis in the world and especially in endemic areas such as Morocco, isolated hepatic and pancreatic tuberculosis and pancreatic tuberculosis remain rare and pose a real diagnostic problem. Case presentation: We report a case illustrating an exceptional association of pancreatic tuberculosis with hepatic tuberculosis in a 44-year-old immunocompetent woman, in whom the presence of a pancreatic mass on imaging suggested a neoplastic origin. The diagnosis was rectified after bacteriological and pathological study of the CT-guided percutaneous biopsy specimens. Discussion: The symptomatology of pancreatic and hepatic tuberculosis is unspecific and polymorphic and can mimic any intra-abdominal pathology. Abdominal ultrasound is often the first imaging modality used. The diagnosis of certainty is bacteriological.The treatment of pancreatic and hepatic tuberculosis is identical to the other extrapulmonary tuberculosis. the anti-bacillary drugs are the gold standard. Surgery is reserved for complicated forms. Conclusion: The diagnosis of hepatic and pancreatic tuberculosis is a challenge for the clinician. The treatment is usually medical and based on antituberculosis treatment; surgery may be necessary in case of complications.

Vascular thromboses with retroperitoneal fibrosis: a case report.

BACKGROUND: Granulomatosis with polyangiitis is a systemic inflammatory disease characterized by necrotizing vasculitis that affects small- and medium-sized blood vessels. Granulomatous inflammation affects the lungs, ears, nose, and throat, and commonly affects the kidneys, although the retroperitoneal tissue is rarely affected. Several studies have reported an increased risk of venous thromboembolism. Early diagnosis and treatment are of vital importance due to the rapid progression of the disease. CASE PRESENTATION: We present the case of a 66-year-old Moroccan man followed for bilateral jugular thrombosis. Cavitary pulmonary nodules and retroperitoneal fibrosis with thrombosis involving several vascular territories were detected on thoracoabdominopelvic computerized tomography scan. Laboratory analyses revealed that the patient was positive for cytoplasmic antineutrophilic antibodies. The diagnosis of granulomatosis with polyangiitis was retained. Treatment with glucocorticoids and immunosuppressive agents resulted in significant clinical and radiological improvement over the following months. CONCLUSIONS: We describe the diagnostic steps and the difficulty of managing this patient. Rare manifestations, such as retroperitoneal fibrosis, have been reported in the literature in association with granulomatosis with polyangiitis, and should not delay the diagnosis and treatment of granulomatosis with polyangiitis owing to its severity.

Unexplained Pleural Effusion Leads to the Revelation of a Malignant Mesothelioma: A Case Report.

Malignant mesothelioma is a rare and aggressive cancer that usually affects subjects with prior asbestos exposure, a major risk factor that has been widely known as carcinogenic, and its use is now controlled if not banned in many areas of the world. Malignant mesothelioma originates from mesothelial surface cells covering the serous cavities, and the pleura is its most common site. Malignant pleural mesothelioma (MPM) typically presents with pleural effusion and chest wall pain with wide pleural thickening at radiological investigation. Although the histological examination along with immunohistochemistry helps yield the diagnosis, clinicians and experts face many challenges in diagnosing malignant mesothelioma not only due to the rarity of the disease but also due to the similarities that the disease share with other malignancies. Here, we report a case of a 55-year-old male patient with a history of chronic asbestos work exposure for 12 years who initially presented with unexplained pleural effusion and chest wall pain and was lost to follow-up but came back later with a worsening clinical state. This case is specially presented to raise awareness against cases of unexplained pleural effusion and chest pain.

Mammary sarcoidosis: A rare case report.

Introduction: Sarcoidosis is an inflammatory, systemic, idiopathic disease characterized by multisystem involvement, of which mediastinal and pulmonary involvement is the most frequent. Mammary sarcoidosis is exceptional. Case presentation: We report the case of a 50-year-old, diagnosed with mediastinal and mammary sarcoidosis. Therapeutic abstention with clinical and radiological surveillance was recommended. The evolution was marked by a clear improvement (clinical and radiological). Discussion: Mammary sarcoidosis is a rare anatomical and clinical entity which poses a problem of differential diagnosis with other granulomatous diseases and especially with breast carcinoma. The coexistence of systemic manifestations should lead to the discussion of sarcoidosis. Conclusion: Mammary sarcoidosis involvement is rare and is manifested by a mass with a smooth or spiculated border, requiring the exclusion of malignancy.

Painful testicular swelling: an unusual localization of sarcoidosis.

Sarcoidosis is a systemic inflammatory disease characterized by non-caseating epitheloid granulomas; whereas it usually involves the lungs and lymph nodes. Testicular sarcoidosis is extremely rare, having been reported to occur in 0.2% of all sarcoidosis patients. We describe a very unusual form of sarcoidosis of the testis, mimicking malignancy at initial presentation.

Intracardiac thrombus in Behçet's disease: a rare case in Morocco.

Behçet's syndrome is a systemic inflammatory disease generally presented with the triad of uveitis, oral and genital ulcers. However, it may present with gastrointestinal, central nervous system, skin and vascular disease manifestations. Intracardiac thrombus is a rare but serious complication of Behçet's disease. A 16-year-old man with Behçet's syndrome was hospitalized into our department with a history of cough, fever, chest pain, hemoptysis, and weight loss. Transthoracic echocardiography and chest scan revealed a right ventricular thrombus. After one month of treatment with cyclophosphamide, and corticosteroid the intracardiac thrombus has been resolved.

[Multifocal tuberculosis complicated by a macrophage activation syndrome: about two cases]. / Tuberculose multifocale compliquée d'un syndrome d'activation macrophagique: à propos de deux cas.

Macrophage activation syndrome (MAS) is a rare disorder due to an inappropriate stimulation of macrophages in the bone marrow and in the lymphoid organs. It is defined based on clinical and cytohistological criteria as well as on laboratory tests. Primary syndrome can occur mostly in children or it can be secondary to different types of disorders: haematological, infectious diseases as well as different types of autoimmune diseases. Prognosis is poor, with a mortality rate of almost 50% from all causes. Treatment is based on specific treatment dependent upon the causative agent of the MAS and, in some cases, on etoposide, corticosteroids and immunogobulines, which should be administered at an early stage. MAS has been rarely described in association with tuberculosis. We here report two cases: an immunocompromised patient, the first case, an immunocompetent patient with multifocal tuberculosis complicated by macrophage activation syndrome, the second case. This study aims to emphasize on difficulty in treating macrophage activation syndrome associated with tuberculosis, on the need for an evaluation of benefit/risk ratio based on corticosteroid or immunosuppressant-related risk for developing immunosuppression, with possible worsening of tuberculosis.