Risk factors for treatment failure in multidrug resistant tuberculosis in Tunisia: An analytic study.

INTRODUCTION-AIM: The emergence of multidrug resistant tuberculosis (MDR-TB) is a threat to global public health. The aim of our study was to determine risk factors for treatment failure in MDR-TB. METHODS: Retrospective study conducted between January 2000 and March 2019 including patients with MDR-TB. Characteristics of patients with therapeutic failure were compared to cured ones. Logistic regression analysis was used to identify risk factors for treatment failure. RESULTS: Our study included 140 patients aged of 42±13 years (18-80). Fifty-seven percent of patients had treatment success and 12% had treatment failure. In multivariate logistic regression analysis, treatment failure was associated with age over 45 years (OR=1.05; 95%CI, 1.024-7.736;p=0.014), primary education level and illiteracy (OR=5.022; 95%CI, 1.316-19.161;p=0,018), history of incarceration (OR=3.291; 95%CI, 1.291-21.083;p=0.016), undernutrition (OR=4.544; 95%CI, 2.304-54.231;p=0,027), extensive TB (OR=6.406; 95%CI, 1.761-23.922; p=0.038), initial high grade positive smears (OR=1.210; 95%CI, 1.187-32.657; p=0.045), positive smear culture at 90 days of treatment (OR=6.871, 95%CI, 3.824-23.541; p=0.003), poor adherence (OR=6.110; 95%CI, 2.740-12.450; p=0.021) and occurrence of psychiatric adverse events (OR=3.644 95%CI, 2.560- 27.268; p=0.041). CONCLUSION: Therapeutic education, nutritional and psychological support and close follow-up are strongly recommended to optimize the prognosis of MDR-TB.

Drug reintroduction testing and beta-lactam hypersensitivity in children: Protocols and results, a 12-year experience.

Introduction: Oral provocation test (OPT) to beta-lactam antibiotics (BL) is a gold standard in allergology investigation. We aimed to demonstrate the contribution of OPT in BL hypersensitivity (HS) indicated as a first step in diagnosis. Methods: We conducted a retrospective study from 2007 to 2019, in a single Tunisian tertiary care academic center. It concerned children with presumed non-severe allergic manifestations to BL, with a reaction that has occurred at least 6 months before the OPT. Results: We identified 35 children for inclusion. After the first OPT, a second OPT with a different BL was performed in case of a positive result of the first one. In 12 cases (34.2%), the OPT elicited a reaction. In eight cases the allergy was to penicillin and in two cases to cephalosporins (cefixim). Cross-reactivity was noted in two cases. Conclusion: An OPT to BL indicated in the first instance in non-severe reaction in children will allow a rapid diagnosis in case of suspicion of HS to BL.

Anaphylaxis following a pleural puncture bringing back a rock water-like liquid.

INTRODUCTION: Anaphylaxis is a life-threatening medical emergency. Its occurrence in the hospital environment should lead to the first evocation of a drug allergy or a latex allergy. However, many other etiologies need to be investigated early. We publish this case report to highlight a rare differential diagnosis of drug allergy, namely hypersensitivity caused by Ecchinoccocus granulosis. CLINICAL CASE: An 18-year-old female patient with no previous pathological history, from a rural environment, consulted for a 4-month history of right basi-thoracic pain without any other associated clinical sign. Her physical examination revealed a right pleuritic syndrome. Chest radiograph showed a right pleural opacity. The patient had a pleural puncture bringing back a rocky water-like fluid. Five minutes later, the patient had an injection of paracetamol to relieve the pain. Thirty minutes later, plaques of urticaria on the extremities and trunk and arterial hypotension occurred. The diagnosis of grade III anaphylaxis was retained. Following vascular filling and administration of antihistamines, the evolution was rapidly favorable. The thoraco-abdominal ultrasound showing the presence of a ruptured liver hydatid cyst in the pleura. A surgical treatment was thus proposed. Despite contact with latex gloves and the administration of paracetamol after surgery, the patient did not present any allergic reaction. Thus the retained cause of the anaphylaxis was ecchinoccocus granulosis. CONCLUSION: Anaphylaxis following a pleural puncture bringing back a rock water-like liquid must suggest the diagnosis of complicated hydatic cyst.

Drainage of tuberculous pneumothorax in a Northern African country: Characteristics and difficulties.

INTRODUCTION-AIM: Tuberculous pneumothorax (TP) is a serious complication of cavitary pulmonary tuberculosis. The aim of this study was to identify TP drainage characteristics and difficulties. METHODS: This was a retrospective multicenter study of patients hospitalized for TP between 1999 and 2021 in three hospitals from Tunis (Tunisia): Abderahmen Mami, La Rabta, and Charles Nicolle. Clinical, biological, radiological, therapeutic and evolutionary data were collected. RESULTS: Seventy-three patients were enrolled. The mean±standard-deviation (SD) of age was 37±17 years. The sex ratio was 3.3. TP was isolated in 39 patients (53.4%) and was associated with a purulent effusion in 34 patients (46.6%). It was bilateral in three patients (4.1%). Chest drainage was indicated in 67 patients (91.7%). It was performed with a chest drain in 61 cases, with a pleuro-catheter in one case, and with a pleuro-catheter then a chest drain in five cases. The mean±SD (ranges) duration of drainage was 43±39 (3-175) days. Drainage was prolonged in 36 cases (53.7%). The duration of drainage for pyopneumothorax was significantly longer than for isolated TP (p=0.04). The mean±SD (ranges) number of drains inserted in each patient was 2.02 ±1 (1-7) drains. Spontaneous drain fall was observed in 13 patients. Drainage failure was observed in 16 patients, and was more frequent in cases of pyopneumothorax (p=0.039). Recurrence of pneumothorax was noted in nine patients (13.4%). CONCLUSION: The drainage of TP is often extended and requires the use of multiple drains. It is associated with several complications. Failure of thoracic drainage is not negligible.

Association of BTLA rs1982809 polymorphism with lung cancer risk in Tunisian population.

B and T lymphocyte attenuator (BTLA) is an immune-inhibitory receptor that negatively regulates the lymphocyte activation. A few studies have been devoted to the relationship between BTLA gene variations and cancer's risk. It has been essentially demonstrated to be involved in increasing cancer risk in chronic lymphocyte leukaemia, renal cell carcinoma, breast and colorectal cancer predispositions in Asian population. The aim of this study was to evaluate the association between BTLA gene polymorphisms and the risk of lung cancer in the Tunisian population. In a case-control study, three BTLA single-nucleotide polymorphism (SNP): rs1982809 (A > G), rs9288952 (G > A) and rs9288953(C > T) were genotyped with the use of TaqMan probes in 169 lung cancer patients and in 300 controls. The rs1982809 SNP was significantly associated with an increased risk of lung cancer compared with controls in codominant and dominant models. The heterozygous rs1982809-AG genotype carriers had a higher risk of developing lung cancer when compared to AA genotype carriers in Tunisian population (OR (95%CI) = 1.63 (1.09-2.42), p = .01]. The AG genotype is an important risk factor associated with lymphatic invasion (OR = 3.71) and large-sized lung tumour (OR = 1.80). It is also a risk factor for the development of an adenocarcinoma subtype (OR = 2.08). However, the BTLA rs9288953 and rs9288952 SNPs were not associated with susceptibility for lung cancer (p > .05). Haplotype comparison did not show any significant association in our research. For the survival analysis, there was no impact of BTLA SNPs on the mortality risk associated to lung cancer in Tunisian patients. The current study is the first to demonstrate an association between BTLA rs1982809 polymorphism and an increased lung cancer risk in the Tunisian population.

ABO blood groups and risk of covid-19.

INTRODUCTION: Coronavirus pandemic has been the subject of a large number of publications, some of which have shown an increased risk of contracting Covid-19 in carriers of blood group A. AIMS: In this study we looked at the profile of blood group phenotype of a series of Tunisian patients with covid-19 admitted to Abderrahman Mami hospital in Ariana . METHODS: Our study included 51 Tunisian patients with SARS-CoV-2 infection admitted to Abderrahmane Mami hospital between late march 2020 and early May 2020. The distribution of blood groups in Covid-19 patients was compared with that of a control group of 1506 patients with no Covid-19 infection as well as with the distribution of blood groups in a population of 63375 voluntary blood donors. RESULTS: Our series, although limited in size, showed a higher prevalence of blood group A among Covid-19 patients, statistically significant compared to ABO blood group distribution among Tunisian blood donors and among a control group of patients without Covid -19. CONCLUSION: these results are in line with data from the literature, particularly on larger series in China.

Does incarceration change the profile of pulmonary tuberculosis in Tunisia?

INTRODUCTION: Tuberculosis of the prisoner remains unknown in Tunisia. The aim of our study was to establish the clinical, radiological, bacteriological and prognostic features of pulmonary tuberculosis in patients with a history of incarceration. METHODS: Case-control study conducted between 2010 and 2016 in two pulmonology departments of Abderrahmane Mami Hospital. The cases were male patients, hospitalized for pulmonary tuberculosis with a history of incarceration. Three controls for one case were randomly selected from the list of male patients hospitalized for pulmonary tuberculosis in the same departments as the cases but with no history of incarceration. RESULTS: The study included 58 cases and 174 controls. The average age of cases was lower than in controls (36,5 years vs 43,4 years; p <0.001). The cases had a significantly worse socioeconomic conditions and educational level with no more frequent social coverage of the disease. Risk factors for TB (smoking, alcoholism, substance abuse, unprotected sex, tuberculosis contagion, viral hepatitis C) were significantly higher among cases. Weight loss and night sweats were significantly more common in both cases, as was undernutrition. Positive bacilloscopies prevailed in the cases (36,5 vs 43,4;p = 0.047). In controls, the institution delay was longer (4.38 days vs 10.24 days; p= 0.004) and the total duration of treatment was lower (7.16 mounths vs 6.55 mounths; p = 0.048). CONCLUSION: Pulmonary TB in prisoner predominates in young people with poor socio-economic status and poor educational attainment. It is associated with several risk factors for TB and malnutrition. Health education in prisons is needed to combat this condition.

Contribution of imaging in the management of resistant tuberculosis.

INTRODUCTION: Resistant tuberculosis is a topical subject given the difficulties of its management. OBJECTIVE: To evaluate the role of imaging in the diagnosis and follow-up of multidrug-resistant tuberculosis (MDR-TB). METHODS: Retrospective study of MDR-TB cases followed in Hall C of Abderrahmane Mami Hospital (2010 to 2016). RESULTS: Forty four patients included. The average age was 33 (15-58). The sex ratio was 1.7. Chest radiographs at the start of treatment showed lesions dominated by nodules (n = 39) and cavities (n = 36). The parenchymal lesions were bilateral (n = 32), associated pleural (n = 4) and mediastinal lesions (n = 7). During treatment, radiological improvement dominated during the first 7 months of treatment. Computed tomography was performed as part of the preoperative assessment of MDR-TB (n = 2), lung cancer extension assessment (n = 1) and etiological assessment of haemoptysis. It allowed to refute a suspected pulmonary embolism (n = 1) and to drain a pleural effusion. Parenchymal lesions on CT were dominated by nodules (n = 8) and cavities (n = 6). Mediastinal nodes (n = 4) and pleural effusions (n = 3) were noted. Ultrasonography showed pleural effusion with pleural thickening (n = 2) and permits its ponction. CONCLUSION: Imaging is a key element in the diagnostic approach to tuberculosis. It permits to evaluate tuberculous lesions and to detect tuberculous complications. It helps to guide the therapeutic management and evaluate its effectiveness.

Allergy to anti-tuberculosis treatment: Place of reintroduction drug test.

BACKGROUND: Allergy to antitubercular drugs is a real hindrance to the management of TB. AIM: To access the contribution of the reintroduction drug test in the exploration of allergy to anti-tuberculosis treatments. METHODS: Retrospective study of 34 patients treated for tuberculosis who presented a hypersensitivity reaction during a period from January 2011 to December 2017. RESULTS: Our study included 31 women (91%) and three men (9%). The average age was 37 years old. The average time to onset of allergic manifestations compared to the start of TB treatment was 23± 19 days (1-85). They were dominated by cutaneous involvement (76.4%). The reintroduction test achieved in 27 patients, allowed to make the diagnosis of allergy to pyrazinamide in 12 patients (44.4%), to Rifampicin in five cases (18.5%), to Ethambutol in one case (3.7%) and isoniazid in one patient (3.7%). A polyallergy was noted in six patients (22.2%). The average time to onset of these reactions was five hours [15mn-90h]. The drug incriminated in the allergy was stopped definitively in 18 patients or 52.9%. It was substituted by a drug of first line in two patients (5.8%) and a second-line drug in three patients (8.8%). Drug dependence was achieved in five patients. It concerned Isoniazid in one patient, Rifampicin in three patients, pyrazinamide in two patients. It allowed the reintroduction of the allergenic treatment noted in two patients. The evolution of tuberculosis was favorable in 26 cases (77%). CONCLUSION: The identification of the allergenic drug is the key to establishing a new protocol for effective anti-tuberculosis treatment that is less risky for hypersensitivity.

Cold abscess in the immunocompetent subject.

INTRODUCTION: Tuberculous cold abscesses are a rare and unusual form, accounting for 1% of extrapulmonary tuberculosis (TB). AIM: To describe clinical, diagnostic, therapeutic and prognostic aspects of cold tuberculous abscesses. METHODS: Retrospective multicentre study of 26 patients followed for cold abscesses tuberculous in respiratory departments of AbderrahmenMami hospital between 2009 and 2017. RESULTS: We included 24 patients. Mean age was 36.9 years. Six patients had a personal history of pulmonary TB. Circumstances of the discovery were chronic pain (n = 15), parietal swelling (n = 7) and parietal fistulization (n = 2). The mean duration of the symptoms was 2.8 months. Fever was absent in 15 patients. The cold abscess was multifocal in 3 patients, associated with pleuropulmonary TB in 16 patients and extrapulmonary TB in 9 patients. Thoracic wall was the most frequent localization (n=13), followed by subcutaneous and intramuscular localization (n = 6). The surgical flattening of the abscess with biopsy of the edges was performed in 15 patients. The positive diagnosis was pathological in 15 patients and bacteriological in 12 patients. GeneXpert was positive in 2 patients. All patients received anti-tuberculosis treatment. The mean duration of TB was 10.7 months. Evolution was marked by the cure of 20 patients and tuberculous relapse in 1 patient after 6 months. CONCLUSION: Tuberculous cold abscess should be evoked in front of any chronique collection occurring especially in a context of risk factors of TB. Early diagnosis is the best guarantee of a cure without complications.

Tuberculosis cost in tunisia.

BACKGROUND: Tuberculosis (TB) infects one third of the world population. Its economic impact is important, affecting the global economy in the World. OBJECTIVE: To determine the economic costs related to tuberculosis in Tunisia. METHODS: Calculations were made for the reference year 2013; we covered all cost components of the disease, which are related to program management, BCG vaccination, health workers training, social mobilization, screening, chemoprophylaxis, and tuberculosis care. With the exception of costs related to care, which were the subject of a specific survey, the costs of other categories were obtained from the National TB Control Program. RESULTS: The cost of the different components related to the management, prevention, screening and tuberculosis care in 2013 amounted 504688,000DT. The cost of care represented 80.0% of total costs (6807 808,000DT) ; cost related to program  management represented 13.2% (1 121 580,00 DT) and the BCG vaccination  6.0% e (512 300,00DT) The average cost per patient was 1447,360 DTin 2013. CONCLUSION: Reducing the cost of tuberculosis, would involve reducing diagnostic delay. It is also recommended to reduce hospitalization recourse, and prevent multidrug resistance which lead to additional expenditures.

Tuberculosis cost in tunisia.

BACKGROUND: Tuberculosis (TB) infects one third of the world population. Its economic impact is important, affecting the global economy in the World. OBJECTIVE: To determine the economic costs related to tuberculosis in Tunisia. METHODS: Calculations were made for the reference year 2013; we covered all cost components of the disease, which are related to program management, BCG vaccination, health workers training, social mobilization, screening, chemoprophylaxis, and tuberculosis care. With the exception of costs related to care, which were the subject of a specific survey, the costs of other categories were obtained from the National TB Control Program. RESULTS: The cost of the different components related to the management, prevention, screening and tuberculosis care in 2013 amounted 504688,000DT. The cost of care represented 80.0% of total costs (6807 808,000DT) ; cost related to program  management represented 13.2% (1 121 580,00 DT) and the BCG vaccination  6.0% e (512 300,00DT) The average cost per patient was 1447,360 DTin 2013. CONCLUSION: Reducing the cost of tuberculosis, would involve reducing diagnostic delay. It is also recommended to reduce hospitalization recourse, and prevent multidrug resistance which lead to additional expenditures.

Evaluation of the microvessel density and the expression of metalloproteases 2 and 9 and ttf1 in the different subtypes of lung adenocarcinoma in Tunisia: a retrospective study of 46 cases.

Despite the new available histologic classification of lung cancers, it remains difficult to assess the real prognostic relevance of the different subtypes of lung adenocarcinomas. Facing the prognostic relevance of microvessel density (MVD) and the expression of metalloproteases and thyroid tyrosine factor 1 (TTF1) in different cancers, we tried to compare these parameters in the different subtypes of lung adenocarcinomas. We conducted a retrospective study of 46 adenocarcinomas surgically resected. An immunohistochemical study using the cluster of differentiation 34 (CD34), TTF1, metalloproteases 2 (MMP2), and metalloproteases 9 (MMP9) antibodies was performed on all samples while MVD was evaluated using CD34 antibody. The analyzed cases included 19 acinar, 7 papillary, 1 lepidic, and 19 solid predominant American Thoracic Classification of lung adenocarcinomas (ASK). The higher MVD levels were observed in papillary and acinar subtypes types and a statically significant difference in the MVD was observed in the different subtypes (p< 0,001). This study didn't show significant statistical results concerning MMP and TTF1 expression but it revealed a tendency to an equal expression of these antibodies in the different subtypes. The difference in the MVD between the different subtypes of adenocarcinoma puts emphasis on their prognostic relevance.

[Evaluation of nutritional Status in lung cancer using bio electrical impedance analysis and mini nutritional assessment]. / Evaluation de l'état nutritionnel par impédencemétrie et Test MNA au cours de cancer primitive du poumon.

BACKGROUND: Malnutrition and cachexia were a frequent problem in lung cancer and increases the risks of morbidity and mortality in these patients. Bioelectrical impedance analysis (BIA) is easy, non-invasive and reproducible method that can be performed. AIM: Evaluate nutritional status in patients with primary lung cancer by Mini Nutritional Assessment (MNA), BIA and anthropometric values (weight, arm and calf circumferences) and correlate the nutritional parameters to severity of cancer and histopathology. METHODS: The nutritional status of 73 cases of primary lung cancer was evaluated by anthropometric parameters, MNA test and impedencemetrie Results: According to body mass index (BMI), malnutrition, overweight and obesity were noted in 34,2%, 13,7% and 5,5%. According to BMI, free-fat mass index (FFMI) and fat mass index (FMI), the investigations occurred malnutrition and depletion of muscle in respectively 19,2% and 23,3% of cases. Fat depletion was noted in 21,9%. Overweight and obesity were detected in 6,8% and 5,5% of cases. Assessment by MNA, revealed that 28,7% of patients were already malnourished and 49,3% of patients were at risk of malnutrition. A significant correlation existed between the score of MNA and arm and calf circumferences, FFMI and FMI. FMI was significantly lower in group of patients with small lung carcinoma. CONCLUSION: Only FFMI allows early detection of malnutrition in cancer patients overestimated by measuring BMI and arm circumference was the better indicator of depletion of muscle.