Relationship between Tuberculin Skin Test and COVID-19 Outcomes among Patients with COVID-19 in Zahedan, Iran.

Background: Ecological studies showed that countries with national Bacillus Calmette-Guerin (BCG) vaccination programs for tuberculosis prevention reported lower incidences of severe and fatal COVID-19 than countries without such programs. Several studies have demonstrated that the BCG vaccine can induce long-term trained Immunity in bone marrow progenitor cells. In this study, we tried to evaluate the relationship between tuberculin skin test results, BCG scar, and COVID-19 outcomes among patients with confirmed COVID-19. Materials and Methods: This was a cross-sectional study. Cases included 160 patients with confirmed COVID-19 in Zahedan hospitals (southeast Iran) in 2020, selected by convenient sampling. PPD test was performed for all patients through the intradermal technique. Collected data included demographic information, underlying conditions, PPD test results, and COVID-19 outcome. Analysis was conducted utilizing ANOVA, χ2 test, and multivariate analysis (logistic regression). Results: The univariate analysis showed a positive relationship between older age, having underlying diseases, and positive tuberculin skin test results with the outcome of COVID-19. We also found a lower frequency of BCG scar among patients with death outcomes than recovered ones. In the multivariate analysis by logistic regression through the backward method, only age and underlying diseases remained predictors of death. Conclusion: Tuberculin test results might be dependent on age and underlying conditions. Our study did not show relationship between BCG vaccine and mortality in COVID-19 patients. Further investigations in different settings are required to reveal the efficacy of the BCG vaccine in preventing this devastating disease.

Spontaneous Multiple Haematomas in a Patient with Severe COVID-19 Fully Recovered with a Conservative Approach.

A significant number of hospitalized patients with COVID-19 are prone to thromboembolic events including deep vein thrombosis, pulmonary embolism, cerebrovascular accident, and myocardial infarction. However, some COVID-19 patients have a higher risk of bleeding that is associated with an increased risk of mortality. We report a 71-year-old woman who was a confirmed case of COVID-19 admitted for pulmonary involvement and complicated acute renal failure. During hospitalization, she suffered from a sudden onset of severe pain in the lower left abdomen as well as a sudden drop in blood pressure and hemoglobin. Haematomas in the left rectus and obturator internus muscle were observed in abdominal and pelvic computed tomography scan. Signs of haemorrhage were also seen in the anterolateral aspect of the bladder with extension to the paracolic, subdiaphragmatic, perihepatic and, perisplenic spaces. The patient was totally recovered by a conservative approach. Bleeding tendency could be a serious complication, especially, in COVID-19 patients with complicated renal failure that receive heparin prophylaxis.

The Prevalence of Absolute and Functional Iron Deficiency Anemia in New Cases of Smear-positive Pulmonary Tuberculosis and Their Sputum Conversion Rate at the End of Intensive Tuberculosis Treatment Phase.

About one third of the population is infected with tuberculosis (TB). On the other hand, iron deficiency is the most common micronutrient deficiency in the world. A number of studies have documented anemia in patients with TB, however, this study aimed to assess the prevalence of iron deficiency anemia (IDA) in patients with acid-fast bacilli (AFB) sputum smear-positive, and sputum conversion in these two groups of patients with absolute and functional IDA at the end of the second month of anti-TB therapy in Zahedan, Iran. The results of this study revealed that 91 out of 198 (45.9%) sputum positive pulmonary TB patients were anemic, and among those 72 (79.1%) had iron deficiency anemia. The overall prevalence of IDA in this study was 36.3%. In 72 patients with IDA, 54 (75%) had functional while the remainder had absolute IDA 18 (25%). Twenty-one out of 72 (29.2%) of patients with IDA remained sputum positive and among 126 non IDA patients 47 (37.3%) had positive sputum smear at the end of intensive TB treatment phase (p=0.278). Approximately, less than half of patients with tuberculosis had anemia among them 79% had iron deficiency anemia. The frequency of functional IDA was three times more than absolute IDA. There was no statistically significant difference in sputum conversion between two groups of IDA and non-IDA patients after intensive phase of anti-TB therapy.

Association between vitamin D receptor polymorphisms and haplotypes with pulmonary tuberculosis.

The vitamin D receptor (VDR) is an important factor in activating immune response in different infectious diseases. The aim of the present study was to investigate the association between the VDR gene polymorphisms and pulmonary tuberculosis (PTB). The case control study was performed on 120 PTB patients and 131 healthy controls. Genetic analysis was performed by polymerase chain reaction and the restriction fragment length polymorphism method. The VDR Fok1 Ff genotype was associated with TB and the risk of PTB was two times higher in individuals with the Ff genotype. A higher frequency of f allele was observed in PTB patients and therefore, the f allele may be a risk factor for PTB susceptibility. There were no associations between the Taq1 and Bsm1 polymorphisms and PTB. In addition, haplotype analysis showed that the f-T-B and f-t-b haplotypes (Fok1, Taq1 and Bsm1) may have the potential to increase PTB susceptibility. In conclusion, the Ff genotype and f allele of the VDR Fok1 polymorphism were associated with PTB susceptibility. In addition, the f-T-B and f-t-b haplotypes may be the susceptible haplotypes for PTB.

Prevalence of crimean-congo hemorrhagic Fever among high risk human groups.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF), an acute viral infection, is a zoonotic disease which is transmitted to humans by infected ticks, direct contact with fresh meat or blood of infected animals (usually domestic livestock), or direct contact with the blood or secretions of an infected person. Livestock handlers, skin processors, veterinary staff, livestock market workers, and other personnel engaged in jobs requiring some contact with animals and/or animal products are at high risk for CCHF. Most reported cases of this disease in Iran belong to butchers and slaughterhouse workers. OBJECTIVES: We aimed to study the prevalence of CCHF in slaughterhouse workers and livestock handlers who were admitted to Boo-ali Hospital for treatment of CCHF. MATERIALS AND METHODS: We evaluated all patients' files with confirmed CCHF admitted to Boo-ali Hospital in Zahedan, in southeastern part of Iran, during 1999-2011. Then, we examined the prevalence of disease among the high risk groups. RESULTS: Out of 362 patients with CCHF (86% male, 14% female; with age range 12-78 years), 123 (34%) were slaughterhouse workers, 103 (28.5%) livestock handlers and farmers, 32 (9%) housewives, 7 (2%) students, 6 (1.9%) teachers, 4 (1.2%) military personnel, and other groups were workers with different employments. CONCLUSIONS: The present study showed that CCHF is highly prevalent in high risk occupational groups in Zahedan, Iran. Further surveillance, teaching and prevention programs are recommended.

Acute Q fever among febrile patients in Zahedan, southeastern Iran.

AIM: So far, few studies have been conducted on Q fever in Iran. The objective of this study was to determine the frequency of acute Q fever in febrile patients admitted to Boo-Ali Hospital in Zahedan (southeastern Iran). MATERIALS AND METHODS: In this study, 105 febrile patients suspected ofhaving brucellosis were examined using indirect immunofluorescent assay kit for the detection of Coxiella burnetii IgM and IgG phase antibodies in their serum. Serum with a phase II IgG titer of > or =256 and a phase II IgM titer of > or =50 was predictive for acute Q fever. Additionally, a 4-fold rise in antibody titers was considered diagnostic of Q fever. Results were analyzed using SPSS 17.0 for Windows. RESULTS: Among 105 patients (male: 52, female: 53), 35.2% (37/105) febrile patients had a positive serology test for acute Q fever. The prevalence of acute Q fever in women and men was 17/37 (45.9%) and 20/37 (54%), respectively. There was serological evidence of past infection in 36 (34.3%) patients. CONCLUSION: According to the results of our study, acute Q fever is highly prevalent in this province. Thus, it is necessary to pay attention to this disease to prevent its transmission in this region.

Factors associated with mortality in tuberculosis patients.

BACKGROUND: Tuberculosis (TB) is one of the main causes of morbidity and mortality in different societies. Understanding factors leading to death following diagnosis of TB is important to predict prognosis in TB patients. The aim of this study was to identify common risk factors associated with death in patients with an in-hospital diagnosis of TB, in a city in Iran with the highest prevalence and incidence of TB in the country. MATERIALS AND METHODS: A retrospective study was conducted at a university-affiliated hospital, Zahedan, in the south-east of Iran, which is a referral center for TB. To identify factors leading to death, medical records of 715 patients ≥15 years old with pulmonary TB from February 2002 to February 2011 have been evaluated. Registered factors included smoking, human immune deficiency virus (HIV) infection, using drugs, lung cancer, drug hepatitis following anti-TB medications, diabetes mellitus, previous TB treatment, anemia; and results of sputum smears. Univariate comparison and multiple logistic regression were performed to identify factors associated with mortality in TB patients. RESULTS: Among 715 registered TB patients, 375 (52.5%) patients were male; among those, 334 (53%) were in the alive group and 41 (54%) in the death group. Seventy-five (10.5%) of the total number of TB patients died during TB treatment. The multivariate model showed that anemia (AOR: 19.8, 95% CI: 5.6-35.5), positive sputum smear (AOR: 13.4, 95% CI: 6.8-33.6), smoking (AOR: 12.9, 95% CI: 3.9-27.3), drug hepatitis (AOR: 12.3, 95% CI: 6.7-24.7), diabetes mellitus (AOR: 9.7, 95% CI: 2.9-32.0), drug use (AOR: 7.8, 95% CI: 2.4-25.5), and history of previous TB (AOR: 6.8, 95% CI: 2.2-21.3) were major risk factors for death in TB patients. CONCLUSION: Monitoring co-morbid conditions like diabetes mellitus and anemia are important to reduce death rate in TB patients. Preventive measures for smoking and drug addiction also play an important role to decrease mortality. Follow-up of patients with previous TB treatment is recommended.

Association between TLR4 and TLR9 gene polymorphisms with development of pulmonary tuberculosis in Zahedan, southeastern Iran.

Some evidence suggests that a variety of genetic factors contribute to development of the tuberculosis (TB). TLR4 and TLR9 have been proposed as susceptibility genes for TB. This study was performed in 124 newly diagnosed TB cases and 149 healthy controls in a TB-endemic region of Iran. The TLR4 genes Asp299Gly, Thr399Ile, and TLR9 gene T-1486C polymorphisms were amplified by polymerase chain reaction (PCR) and then detected by PCR-restriction fragment length polymorphism (RFLP). The frequencies of the mutant alleles of TLR4 Arg299Gly, Thr399Ile, and TLR9 T-1486C polymorphisms were 0.8 versus 0.1, 5.6 versus 3, and 28.6 versus 25.2 in patients and controls, respectively, that were not significant. The synergic effect of TI,II/CC genotypes for TLR4 Thr399Ile and TLR9 T-1486C polymorphisms showed increased risk of PTB susceptibility. In conclusion, no significant relation was found between TLR4 and TLR9 polymorphisms alone and PTB. However, synergic effects of TLR4 Thr399Ile and TLR9-1486T/C polymorphisms might increase risk of PTB.

Efficacy of high-dose methylprednisolone in patients with Crimean-Congo haemorrhagic fever and severe thrombocytopenia.

Crimean-Congo haemorrhagic fever (CCHF) is an acute viral haemorrhagic disease that is now endemic in south eastern Iran. The most important factor associated with mortality is a platelet count of less than 50,000/mL. The purpose of this study is to compare treated cases with severe thrombocytopenia using ribavirin with high-dose methylprednisolone (HDMP) with patients receiving ribavirin without HDMP. A clinical trial was conducted for confirmed patients with CCHF and severe thrombocytopenia (platelet count less than 50,000/mL) admitted to Boo-Ali Hospital in Zahedan between January 2010 and October 2011. The intervention group was given oral ribavirin, supportive managements and HDMP and the controls were treated with ribavirin and supportive management. Following HDMP therapy in hospitalized patients with severe thrombocytopenia, the platelet count increased within 36 h and the leukocyte count within 48 h of the beginning of treatment. Fewer in the intervention group required a transfusion of blood products than in the controls (P < 0.001). No one in the intervention group died. It seems that high-dose methylprednisolone is effective in the treatment of patients with CCHF. The increased platelet count and reduction of blood product requirement for severe CCHF patients after receiving HDMP are promising results. Further investigation is necessary in order to determine the efficacy of corticosteroid and its effect on outcome.

Cranial nerve palsy as a factor to differentiate tuberculous meningitis from acute bacterial meningitis.

Tuberculous meningitis (TBM) and acute bacterial meningitis (ABM) cause substantial mortality and morbidity in both children and adults. Identification of poor prognostic factors at patient's admission could prepare physicians for more aggressive monitoring of patients with meningitis. The objective of this study was to determine the predictive value of neurological features to differentiate ABM and TBM. A retrospective study was conducted between patients affected with ABM or TBM admitted to three teaching hospitals during the last 14 years in Zahedan the central city of Sistan and Balouchestan province (Iran). The neurological features include seizure, level of consciousness, stroke, focal neurologic deficit and cranial nerve palsy at the time of admission. Mean age for patients with TBM and ABM were 41 ± 22.4 and 24 ± 18.5 years respectively. In univariate analysis, all measured variables revealed significant difference between ABM and TBM patients except for seizure episodes. Multivariate logistic regression analysis showed positive predictive effect of cranial nerve palsy (AOR=1.980, CI 95%: 1.161-3.376) on the diagnosis of TBM. In our study cranial nerve palsies was the most important neurological predictor factor to differentiate TBM from ABM.

Infective causes of stroke in tropical regions.

Vascular diseases of the brain are the second reason of the death and the first cause of morbidity and disability worldwide. In tropical areas stroke has some particular features related to the nature of torrid zones. There are some special causes of the stroke, mainly infectious, although some of them are non-infectious. The most important etiologies are malaria, tuberculosis, cysticercosis, syphilis, and Chagas' disease. The mean age of the patients with stroke in tropical areas seems to be less than that in developed countries, and the disease is more prevalent in younger adults. Prevention and/or treatment of the classic risk factors as well as factors related to tropical zones are the mainstays of controlling the disease. It has to be mentioned that lack of human as well as financial resources makes it difficult to control and treat the disease properly. Herein, the etiologies and risk factors of the cerebrovascular diseases in tropical regions will be reviewd.

Clinical and laboratory diagnosis of the patients with sputum smear-negative pulmonary tuberculosis.

BACKGROUND: The objective of this study is to describe the proportion of patients with chronic cough and negative smear microscopy appropriately diagnosed as tuberculosis (TB) and to identify clinical features that could be used in developing a diagnostic scoring system for smear-negative patients. METHODS: Records of patients with chronic cough and ≥ 3 negative sputum smears for acid fast bacilli who attended a reference University hospital in south-eastern Iran and screened by culture were retrospectively reviewed. We compared confirmed smear-negative pulmonary TB (PTB; culture-positive) and unconfirmed smear-negative patients (culture-negative) to describe the appropriateness of treatment and their characteristics. Features independently predictive of smear-negative PTB (SNPTB) were entered into a logistic regression to create a diagnostic rule. RESULTS: This study enrolled 350 patients, of which 52 (14.8%) were culture-positive and 298 (85.2%) culture-negative. Of these, 38 out of 52 (sensitivity 73%) confirmed SNPTB were diagnosed as TB and 283 out of 298 (specificity 95%) unconfirmed sputum-negative patients were diagnosed as non-PTB. Variables associated with confirmed SNPTB were the presence of night sweats, family history of TB, typical chest radiography, erythrocyte sedimentation rate > 45 mm and white blood cell count < 11000/mL. The score constructed with these variables had a sensitivity of 94% and specificity of 74% with an area under the curve of 0.90. CONCLUSION: The clinical differences between SNPTB and control patients could be used to develop a clinical scoring system to identify patients with SNPTB.

Association between tuberculosis and smoking.

BACKGROUND: The association between smoking and tuberculosis (TB), which has been proven in multiple studies with different study population ethnicity, has not yet received sufficient attention in terms of TB control. OBJECTIVES: The aim of the present study was to determine the association between TB and cigarette smoking in southeastern Iran, an endemic area for tuberculosis. PATIENTS AND METHODS: This prospective case-control study conducted at a University-Affiliated Hospital (Boo-Ali Hospital, Zahedan, and Southeastern Iran) from March 2007 to March 2012 enrolled 253 TB patients and 312 healthy controls. Factors including history of cigarette smoking, duration of smoking, number of cigarettes smoked per day, consumption of other drugs (parenteral and non-parenteral), and family history of tuberculosis and smoking, were evaluated in both cases and controls. Univarate and multivariate logistic regressions were performed to compare TB cases and controls. The odds ratio (OR) and 95% confidence intervals (CI) were also estimated. RESULTS: The results of the study revealed a significant difference between TB and control groups in relation to smoking (P < 0.0001). In multivariate logistic regression, cigarette smokers were 3.1 (95% CI: 1.4-10.3) times more frequent in TB patients compared with controls. Other factors that showed significant differences between TB patients and controls were the use of non-parenteral drugs (OR = 3.6, 95% CI: 2.2-21.4), family history of TB (OR = 6.6, 95% CI: 2.3-18.2), family history of smoking (OR = 2.8, 95% CI: 1.1-8.4), and smoking history of more than 10 years (OR = 1.6, 95% CI: 1.2-9.8). CONCLUSIONS: The present study evidenced the association between TB and smoking. It is therefore recommended to include interventions for smoking cessation in the current TB control practice.

Comparative analysis of cerebrospinal fluid adenosine deaminase in tuberculous and non-tuberculous meningitis.

OBJECTIVE: To calculate cut-off point for the adenosine deaminase (ADA) activity in the CSF of patients with tuberculous meningitis (TBM). PATIENTS AND METHODS: The ADA assay was based on the automatic indirect method in which ADA catalyzes adenosine to inosine. ADA activity in the CSF was calculated based on ammonia liberated from adenosine and quantified spectrophotometrically. Arithmetic mean values and standard deviation of each variable were measured. Mann-Whitney U and Fisher exact tests were applied to compare continuous and dichotomous variables between tuberculous and non-tuberculous groups. A receiver operating characteristic curve was plotted to identify various cut-off points to determine the best level for ADA activity. RESULTS: Totally 42 patients were enrolled into the study. The median of ADA activity in the TBM group was 22 and in the non-TBM group was 8.0. The mean CSF-ADA activity was found to be significantly higher in TBM group (23.05+/-13.1IU/L) than in the CSF from non-TBM patients (9.39+/-5.18IU/L). The highest accuracy is at the cut-off value of 10.5IU/L. The sensitivity and specificity of the test at this cut-off to differentiate TBM from non-tuberculous meningitis is 81% and 86% respectively. CONCLUSION: Considering that a high positive value of ADA activity cannot confirm TBM, however, in suspected patients it may lead the physician to treat patient earlier before the confirmatory diagnostic reports will be received. The suggested cut-off value in this pilot study is 10.5IU/L with high sensitivity and specificity.

Diagnostic risk factors to differentiate tuberculous and acute bacterial meningitis.

The objective of this study was to identify independent predictor factors for diagnosis of tuberculous meningitis and develop a clinical prediction tool based upon a set of simple clinical and laboratory parameters in our local population. Clinical and laboratory features were compared in 68 patients with tuberculous meningitis and 123 cases of acute bacterial meningitis in 3 referral centres for tuberculosis in south-eastern Iran. Twenty-two clinical and laboratory features were analysed. Based on the best-fitted model a receiver operating characteristic curve with the highest surface under the curve was constructed. Disease duration before diagnosis (>or=5 d) had the highest odds ratio of 21.9. Age over 30 y, CSF leukocyte count or=70% were placed after disease duration with odds ratios of 5.1, 3.7 and 2.6, respectively. Sensitivity, specificity and likelihood ratio for a positive test in this model were 84%, 88% and 7.4, respectively. The area under the ROC curve was 0.92. It appears that a single model can not predict TBM diagnosis in different populations. Using clinical and laboratory parameters may facilitate empirical diagnosis of TBM in endemically low income countries with limited microbiological diagnostic facilities.

An old man with a mass in the retropharyngeal space.

In this article, we discuss clinical manifestations, laboratory results, and radiological findings in an old man with suppurative tender mass in the neck, accompanied by, fever, weight loss, malaise, fatigue, night sweat, cough, vomiting, and dysphagia. Pharyngeal exam revealed a huge retropharyngeal abscess.

Patho-TB test for the rapid diagnosis of pulmonary tuberculosis.

BACKGROUND: Despite recent technologic improvements in identifying mycobacterium tuberculosis, we are still facing problems in rapid diagnosis of tuberculosis. The objective of this study is to determine the diagnostic value of a new rapid screening test (Patho-TB™) for diagnosis of pulmonary tuberculosis. METHODS: Between September 2006 to August 2007, 178 patients were enrolled in the study who were finally classified into two groups; a group of documented pulmonary tuberculosis (n = 67) and a group of non-tuberculous pulmonary infection (n = 111). Patho-TB™ test, Ziehl-Neelsen staining and culture were done on all specimens. RESULTS: Of all, 43 patients with pulmonary tuberculosis were sputum smear positive for acid fast bacilli and the rest were smear negative. Mean age of the patients was 59.8 ± 16.1 years and 44% of them were men. The results of Patho-TB™ test were positive in 40 of smear positive and 20 of smear negative tuberculous patients and 33 cases of non-tuberculous control group. The sensitivity, specificity, positive and negative predictive values and accuracy of Patho-TB™ test were estimated 89.5%, 70.2%, 64.5%, 91.7% and 77.5%, respectively. CONCLUSIONS: According to the present study it would be suggested that Patho-TB™ test could be a rapid and inexpensive method for diagnosis of pulmonary tuberculosis, given by its high sensitivity and negative predictive value. Concerning the high number of false positive results, using a confirmatory diagnostic procedure is mandatory.