Anti-tuberculosis Drug Treatment Research Articles

INTENSIVE TREATMENT OF A CAPTIVE BORNEAN ELEPHANT (ELEPHAS MAXIMUS BORNEENSIS) INFECTED WITH MYCOBACTERIUM CAPRAE IN JAPAN.

In 2015, an estimated 17-year-old female Bornean elephant (Elephas maximus borneensis) at Fukuyama Zoo in Japan exhibited anorexia and significant weight loss. Pan-susceptible Mycobacterium tuberculosis complex (MTBC) was isolated from vaginal discharge, oral mucus, urine, and fecal samples by culture. The isolate was identified as Mycobacterium caprae by genetic analysis. Isoniazid, pyrazinamide, and levofloxacin were administered rectally. Body weight increased to normal, but subsequently decreased again. Elevation of liver enzymes occurred, likely related to the increase in isoniazid dosage. After recovery from side effects, the elephant's weight increased further. However, isoniazid-resistant M. caprae was isolated from oral mucus after anti-tuberculosis drug treatment for 9 mo. The regimen was changed to rifampicin, pyrazinamide, ethambutol, and levofloxacin, administered orally or rectally. The 18-mo treatment was completed in October 2018. This elephant has shown no clinical sign since. No MTBC-positive sample had been obtained as of March 2020.

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Aim: to study the attitude of patients with tuberculosis (TB) toward disease and treatment. Materials and methods. Anonymous questioning of 490 patients with TB grouped by case category (new, repeated treatment, multiple-resistant TB) and phase of treatment (intensive or maintenance phase, hospital or out-patient). Statistical analysis of the results was performed. Results. Majority of study participants were aware about TB, duration of its treatment and commonly used antituberculosis drugs (ATD). But 1/3 of patients was not informed on possible side effects of ATD. Many patients trusted their physician, had good relationships with medical personnel. They were sure about the cure and readily accepted ATD treatment, confirmed a support of relatives and friends. However, many patients were depressed due to the longevity of treatment (59,8 %), 31,8 % had doubts regarding convalescence, 56,5 % needed psychological support. 55,9 % of hospital patients wished to receive an out-patient care. 1/3 of hospital patients were unsatisfied by the conditions of the facilities. 14,4 % of patients anticipated the changes in organization of out-patient treatment. The considerable worsening of quality of life was noted in 59,2 % of patients: 70,0 % of these patients considered this was due to financial burden, 54,8 % � poor physical condition, 46,6 % � the change of lifestyles, 12,8 % � emotional suffering. 63,3 % of interviewed patients considered that there was a �brand of TB patient� in society: 1/2 of patients felt this on their own, 59,0 % concealed the fact of the illness. Patients with multiple-resistant TB had less support from relatives and friends, less trusted their physician, needed more psychological support. They were less sure in convalescence and more frustrated by the long treatment. They wanted to be treated as out-patients; felt the worsening of quality of life and bad attitude from the society. Conclusions. Questioning of TB patients has revealed the following: lack of knowledges about possible side effects of ATD, need for shorter duration of therapy, better hospital treatment conditions or opportunity to get treatment at home, doubts in convalescence and necessity for psychological support, need for better quality of life (financial and emotional condition, lifestyles), possibility not to conceal the illness because of negative attitude in society and need to improve the conditions of treatment. It was proved the necessity for improvement of patients' awareness about TB course and treatment, provision of psychological support (especially in resistant TB), improvement of hospital and outpatient care (considering patient�s expectations and epidemic safety), elucidative work with their nearest surroundings and creation of such informative environment in society, which would overcome negative attitude toward with TB patients. Findings are important for the improvement of organization of treatment and achievement of better treatment adherence of the patients, and can positively influence overall treatment effectiveness. Key words: tuberculosis, disease, treatment, questioning.

Lipid peroxidation aggravates anti-tuberculosis drug-induced liver injury: Evidence of ferroptosis induction

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common adverse reaction of anti-tuberculosis drug treatment. Studies have shown that isoniazid (INH) and rifampicin (RFP) are mainly metabolized in the liver and a large amount of intracellular glutathione is used up during the metabolism of these drugs, resulting in lipid peroxidation and hepatocyte death. Ferroptosis is a novel form of programmed cell death caused by iron-ion-dependent lipid peroxidation. In this study, we explored lipid peroxidation and ferroptosis during ATB-DILI. Morphology of ferroptosis was discovered in ATB-DILI mouse livers by transmission electron microscopy. Flow cytometry was used to assess the molecular markers of lipid peroxidation and ferroptosis including reactive oxygen species, lipid peroxidation, and cellular iron content. Glutathione peroxidase 4 (GPX4) was depleted, while acyl-CoA synthetase long chain family member 4 (ACSL4) was overexpressed in the ATB-DILI tissues. And glutathione supplementation significantly reduced the level of lipid peroxidation and the risk of liver damage. Retrospective study of tuberculosis patients who underwent INH and RFP treatment also revealed an association between the intake of glutathione and a negative ATB-DILI rate. In addition, iron supplementation enhanced the degree of lipid peroxidation and liver injury induced by INH and RFP in vivo and clinical retrospective study. Taken together, these results indicate that lipid peroxidation and evidence suggestive of ferroptosis occurs during ATB-DILI, and glutathione replenishment prevents this process while iron supplementation augmenting this effect.

Effect of Iron Supplementation in Anti-Tuberculosis Drug Treatment on Interferon-γ Level in Tuberculosis Spondylitis Patients

Tuberculosis (TB) is still one of the major health problems in the community. Micronutrients, including iron, are crucial in the body's defense mechanism. Iron modulates the activation of IFN-γ, which in turn will activate the macrophages. This study explores the effect of iron supplementation given with anti-tuberculosis drug therapy on the IFN-γ level in tuberculosis spondylitis patients. This was a single-blind randomized control trial study at Dr. Hasan Sadikin General Hospital Bandung, from December 2018 to March 2019, using the consecutive sampling approach. Thirty-four respondents with category 1 TB spondylitis and an sTfR level of> 21.7 pg /µL were recruited and randomized into control and experimental groups. The control group (n=17) was treated with 2 RHZE for 2 months while the experimental group (n=17) received 2 RHZE and iron tablet for 2 months. An increase in the IFN-γ level of the experimental group was observed from an average of 21.7 pg/ml before therapy to an average of 72.39 pg/mL after therapy. Meanwhile, the IFN-γ level in the control group increases from an average of 22.5 pg/mL to an average of 35.35 pg/mL. This difference was statistically significant based on the analysis using the independent t-test (p-value <0.05). Therefore, the administration of anti-tuberculosis drugs with the addition of iron can increase the body's immune response, which is indicated by the increasing level of IFN-γ.

Correlation between intensive phase treatment of antituberculosis drugs with nutritional status of patients with tuberculosis in Kupang city

Background: Indonesia is a country with the third highest tuberculosis incident in the world. Nutritional status is very important to patients with tuberculosis, an optimal nutritional status created an optimal immune system. Lack of adequate nutritional intake, prolonged the anti-tuberculosis drug treatment and caused them to get a slower recovery. Therefore, the writer found the need of knowing the relation of intensive phase treatment of anti-tuberculosis drugs with nutritional status of patients with tuberculosis in Kupang City.Objectives: To know the relation between intensive phase treatment of anti tuberculosis drugs with nutritional status of patients with tuberculosis in Kupang City.Methods: This study was an observational analytic study with a nested cohort design conducted by 11 public health centers in Kupang City by taking secondary data from medical records. The sampling technique used consecutive sampling with 84 respondents who met the inclusion and exclusion criteria. The study was analyzed univariately, and bivariately using Mc Nemar.Results: From 84 respondents, before intensive phase tuberculosis treatment 61 respondents (72.6%) had abnormal nutrition status, and 23 respondents (27.4%) had normal nutritional status, while after intensive phase tuberculosis treatment from 84 respondents it was found that 50 respondents (59.5%) had abnormal nutrition status, and 34 respondents (40.5%) had normal nutritional status. The result of the bivariate analysis test shows a significant different in nutritional status before and after tuberculosis treatment with p value = 0.001.Conclusions: There was a significant different in nutritional status before and after tuberculosis treatment indicating that anti-tuberculosis drug treatment can affect the nutritional status of patients with tuberculosis.Cl

Pharmacokinetics and Pharmacodynamics of Intensive Antituberculosis Treatment of Tuberculous Meningitis.

The most effective antituberculosis drug treatment regimen for tuberculous meningitis is uncertain. We conducted a randomized controlled trial comparing standard treatment with a regimen intensified by rifampin 15 mg/kg and levofloxacin for the first 60 days. The intensified regimen did not improve survival or any other outcome. We therefore conducted a nested pharmacokinetic/pharmacodynamic study in 237 trial participants to define exposure–response relationships that might explain the trial results and improve future therapy. Rifampin 15 mg/kg increased plasma and cerebrospinal fluid (CSF) exposures compared with 10 mg/kg: day 14 exposure increased from 48.2 hour·mg/L (range 18.2–93.8) to 82.5 hour·mg/L (range 8.7–161.0) in plasma and from 3.5 hour·mg/L (range 1.2–9.6) to 6.0 hour·mg/L (range 0.7–15.1) in CSF. However, there was no relationship between rifampin exposure and survival. In contrast, we found that isoniazid exposure was associated with survival, with low exposure predictive of death, and was linked to a fast metabolizer phenotype. Higher doses of isoniazid should be investigated, especially in fast metabolizers.

Effect of Mycobacterium tuberculosis Enhancement of Macrophage P-Glycoprotein Expression and Activity on Intracellular Survival During Antituberculosis Drug Treatment.

Tuberculosis is caused by Mycobacterium tuberculosis. Recent emergence of multidrug-resistant (MDR) tuberculosis strains seriously threatens tuberculosis control and prevention. However, the role of macrophage multidrug resistance gene MDR1 on intracellular M. tuberculosis survival during antituberculosis drug treatment is not known. We used the human monocyte-derived macrophages to study the role of M. tuberculosis in regulation of MDR1 and drug resistance. We discovered that M. tuberculosis infection increases the expression of macrophage MDR1 to extrude various chemical substances, including tuberculosis drugs, resulting in enhanced survival of intracellular M. tuberculosis. The pathway of regulation involves M. tuberculosis infection of macrophages and suppression of heat shock factor 1, a transcriptional regulator of MDR1 through the up-regulation of miR-431. Notably, nonpathogenic Mycobacterium smegmatis did not increase MDR1 expression, indicating active secretion of virulence factors in pathogenic M. tuberculosis contributing to this phenotype. Finally, inhibition of MDR1 improves antibiotic-mediated killing of M. tuberculosis. We report a novel finding that M. tuberculosis up-regulates MDR1 during infection, which limits the exposure of M. tuberculosis to sublethal concentrations of antimicrobials. This condition promotes M. tuberculosis survival and potentially enhances the emergence of resistant variants.

Characteristics and risk factors for antituberculosis drug-induced liver injury in a cohort of patients with cirrhosis in a tertiary referral university teaching hospital in Thailand

Abstract Background Cirrhotic patients are susceptible to drug toxicity, which presents frequently with antituberculosis drug (ATD) treatment. Previous studies of ATD-induced liver injury (ATDILI) in cirrhotics have been limited to patients with early-stage cirrhosis. Objectives To describe characteristics and determine risk factors for ATDILI in cirrhotic patients. Methods We included 64 cirrhotic patients treated with ATDs between 2006 and 2016 in a tertiary referral university teaching hospital in Bangkok, Thailand. Cirrhosis was diagnosed by radiological features, including small-sized nodular liver and/or caudate lobe hypertrophy or evidence of portal hypertension (collateral vessels, varices, and/or splenomegaly). Clinical information was retrospectively abstracted. Characteristics of patients with ATDILI vs. those without ATDILI were compared. Results Six (9.4%) patients developed ATDILI with the median duration from ATD initiation of 14 days (range: 6–66). All the 6 patients who developed ATDILI received 3 hepatotoxic ATDs (isoniazid, rifampin, and pyrazinamide) and had Child–Turcotte–Pugh class B cirrhosis. The patients with ATDILI were found to have a higher percentage of human immunodeficiency virus (HIV) infection than patients without ATDILI (50% vs. 8.6%; P = 0.02). Conclusions Cirrhotic patients, particularly those with underlying HIV infection, are at risk of developing ATDILI. Pyrazinamide should be used cautiously in cirrhotic patients due to the significantly increased risk of ATIDLI. This study supports the current recommendation for the use of ATD in patients with cirrhosis; however, the ATD regimen should be carefully selected, particularly for cirrhotic patients with HIV infection.

The Changes of Interleukin 17 levels On Pulmonary Tuberculosis Patients with AFB Smear-Positive After 2 Months Anti Tuberculosis Drugs Treatment

Background: Tuberculosis still remain as a health problem in the world. No specific biomarkers can be used to monitor the rapid response to TB therapy. This study aims to assess the change of IL-17 levels in pulmonary tuberculosis patients with AFB smear-positive before and after 2 months of anti tuberculosis drugs (ATD) treatment.
 Method: Design of study is analytic observational with prospective cohort. The subject include 17 new cases of pulmonary tuberculosis patients with AFB smear-positive in Soetomo Hospital Surabaya from July - October 2016. Plasma levels of IL-17 were measured using ELISA technique before treatment and 2 months after the ATD therapy.
 Results: The mean levels of IL-17 before treatment is 3.510 pg / ml (2.087- 5.051 pg/ml). There were significantly decreament (p = 0.001

Immunotherapeutic potential of an N-formylated peptide of Listeria monocytogenes in experimental tuberculosis

Objective: The current therapeutic regimens for tuberculosis (TB) are complex and involve the prolonged use of multiple antibiotics with diverse side effects that lead to therapeutic failure and bacterial resistance. The standard appliance of immunotherapy may aid as a powerful tool to combat the ensuing threat of TB. We have earlier reported the immunotherapeutic potential of N-formylated peptides of two secretory proteins of Mycobacterium tuberculosis H37Rv. Here, we investigated the immunotherapeutic effect of an N-formylated peptide from Listeria monocytogenes in experimental TB.Methods: The N-terminally formylated listerial peptide with amino acid sequence ‘f-MIGWII’ was tested for its adjunctive therapeutic efficacy in combination with anti-tuberculosis drugs (ATDs) in the mouse model of TB. In addition, its potential to generate reactive oxygen species (ROS) in murine neutrophils was also evaluated.Results: The LemA peptide (f-MIGWII) induced a significant increase in the intracellular ROS levels of mouse neutrophils (p ≤ .05). The ATD treatment reduced the colony forming units (CFU) in lungs and spleen of infected mice by 2.39 and 1.67 log10 units, respectively (p < .001). Treatment of the infected mice with combination of ATDs and LemA peptide elicited higher therapeutic efficacy over ATDs alone. The histopathological changes in the lungs of infected mice also correlated well with the CFU data.Conclusions: Our results clearly indicate that LemA peptide conferred an additional therapeutic effect when given in combination with the ATDss (p < .01) and hence can be used as adjunct to the conventional chemotherapy against TB.

Efficacy of acupressure to prevent adverse reactions to anti-tuberculosis drugs: Randomized controlled trials.

To determine whether acupressure can prevent or relieve the adverse drug reactions (ADRs) of anti-tuberculosis drugs. People receiving drug treatment for TB often experience ADRs that may cause them to stop taking their medication. Acupressure is a form of traditional Chinese medicine that can be applied to alleviate or prevent disease symptoms. A double-blinded, repeated-measures clinical trial in hospitals in Taiwan was carried out from April 2015 - May 2017. Convenience sampling was used to select 32 people (15 for the experimental group and 17 for the control group) aged >20years who were taking anti-tuberculosis drugs. The people were randomized to receive 4-week of true acupressure and 4-weeks of sham acupressure. Acupressure therapy was given by a researcher in all cases. Both groups received treatment once per day on weekdays, with 15min for each acupressure session. Outcomes (gastrointestinal irritation and adverse skin reactions) were assessed according to the people feedback and the physicians' recordings during the treatment course, and during monthly follow-up visits for 6months thereafter. Both groups typically experienced gastrointestinal irritation and adverse skin reactions within 2months of beginning anti-tuberculosis drug treatment. The 4-weeks intervention involving relevant acupressure points successfully relieved both types of side effects in both immediate and delayed manner. When correctly implemented, acupressure can prevent and relieve the ADRs of anti-tuberculosis drugs, and motivate people to complete their treatment course.

FACTORS THAT INFLUENCE THE INCIDENCE OF DRUG INDUCED LIVER INJURY IN PULMONARY TUBERCULOSIS PATIENT

Background: The use of anti-tuberculosis drugs (ATD) is not uncommon to find side effects that complicate treatment. One of the side effects caused by ATD treatment is Drug Induced Liver Injury (DILI). Risk factors that trigger the incidence of DILI during tuberculosis (TB) treatment involving variety of factors. This study was conducted to determine the risk factors of DILI in pulmonary tuberculosis patient. Method: Conducted retrospective case-control study. Study subjects were all patients who underwent first category ATD treatment at Dr. Wahidin Sudirohusodo hospital of Makassar, Indonesia. Risk factors examined were age, gender, nutritional status, alcohol consumption, smoking, history of liver disease, consumption of other drug, ATD preparation of Fixed Dose Combination (FDC) and abnormality of SGPT/ total bilirubin control value at minimum of 2 weeks after starting treatment. Result: from total 47 samples who took part in the study, 10 samples (21.3%) suffered DILI. Samples characteristics who suffered from DILI, were an average age of 52.7 years old (P < 0.05), and consumption of other drug 29.4% (P < 0.05). There was no significant relationship between gender, nutritional status, alcohol consumption, smoking, and history of liver disease in the incidence of DILI. Conclusion: Old age and history of consumption of other drug has significant relationship as a risk factors for the incidence of DILI in TB patients who consume ATD, while no significant relationship found between gender, malnutrition, alcohol consumption, smoking, and history of liver disease.

Multiple surgical radical treatment in axillary lymph nodes: A case report

Lymph node tuberculosis is a common clinical bacterial infectious disease. Regional lymph node tuberculosis is often difficult to cure by surgically radical resection. In addition, its recurrence rate is higher, and it can easily cause lymphatic leakage. This case was considered to have left axillary lymph node tuberculosis. A combination of clinical examination, ultrasound, and magnetic resonance imaging examinations were performed before surgery. The surgical procedure performed was left axillary lymph node excision. Postoperative pathology confirmed the lymph node tuberculosis. The patient was given anti-tuberculosis drug treatment with no recurrence after 6 months follow-up. This provides new ideas and methods for the clinical treatment of regional lymph node tuberculosis.

Antituberculosis Drugs Resistance and Treatment Outcomes Among Retreatment Patients in Guinea: A Five-Year Retrospective Cohort Study

Tuberculosis (TB) is a global outbreak whose drug resistance is a constant threat. This study aimed at describing anti-TB drugs resistance and treatment outcomes among retreatment TB patients in Guinea between 2008 and 2012. We conducted a retrospective cohort study with a sample of 558 patients aged of at least 10, who were admitted for TB retreatment and who were tested for anti-TB drugs susceptibility during the study period. Overall, 3187 retreatment TB patients were recorded from January 1, 2008 to December 31, 2012 in Guinea, of which 558 (17.5%) performed susceptibility testing to anti-TB drugs. We found overall resistance in 417 cases (74.7%) including 356 (85.4%) of multidrug resistance (MDR), 29 (6.9%) of monoresistance (isoniazid 2.9%, streptomycin 2.9%, rifampicin 0.9%, ethambutol 0.2%) and 32 (7.7% of polydrug resistance (isoniazid + streptomycin 4.3%, rifampicin + streptomycin 1.4%, isoniazid + ethambutol + streptomycin 1.0%, rifampicin + ethambutol + streptomycin 1.0%). Most of the patients (84.6%) with anti-TB drugs resistance were under 45 and labourers were mostly represented (27.8%) including drivers in majority (37.9%). MDR-TB incidence rate increased by 12.2% between 2008 (65.6%) and 2012 (77.8%), and the annual cure rate decreased gradually from 60.0% in 2009 to 45.7% in 2012. Among MDR-TB patients (n= 356), only 112 (31.5%) benefited from second-line treatment regimen, of which, 51.7% were cured, 6.3% completed treatment, 24.1% died, 6.3% were lost to follow-up and 11.6% were not evaluated. The cure rate was higher in HIV-negative patients (55.3%) than in those who were HIV-positive (35.3%) and the death rate was the highest (41.2%) in HIV-positive patients. Overall, treatment success rate was 58.0%. This study revealed a low rate of performing drug susceptibility testing, the gradual increase of the incidence of MDR-TB each year and the gradual decrease of cure rate from year to year. Besides, anti-TB drugs resistance concerned mostly drivers in our context. Prospective studies are needed for a deep understanding of the factors associated with these persistent challenges.

Path Analysis on the Determinants of Adherence to Anti Tuberculosis Drug Treatment in Kaur District, Bengkulu, Indonesia

Background: Drug treatment compliance was the behavior of patients to take medication and undergo treatment according to the rules determined by professional health personnels. Many factors influenced the compliance with treatment for tuberculosis patients. This study aimed to examine determinants of drug treatment compliance among tuberculosis patients. Subject s and Method: This was an analytic observational study with a cross-sectional design. The study was conducted at 16 community health centers in Kaur Regency, Bengkulu, Indonesia, from January to February 2019. A sample of 206 study subjects was selected by purposive sampling. The dependent variable was drug treatment adherence. The indepen­dent variables were age, gender, education, income, knowledge, role of drug taking supervisor, side effect of drug treatment, distance to health service, drug availability, family support, and tenure. The data were collected by questionnaire and analyzed by path analysis. Results : Adherence to anti tuberculosis treatment was directly and positively affected by age (b= 2.96; CI 95%= 1.12 to 4.79; p= 0.002), gender (b= 1.48; CI 95%= 0.02 to 2.95; p= 0.047), education (b= 2.18; CI 95%= 0.24 to 4.11; p= 0.027), income (b= 0.85; CI 95%= 0.76 to 2.45; p= 0.031), knowledge (b= 2.27; CI 95%= 0.32 to 4.22; p= 0.023), the role of drug taking supervisor (b= 3.46; CI 95%= 1.57 to 5.36; p<0.001), drug availability (b= 0.04; CI 95%= -6.07 to 6.16; p= 0.989), and family support (b= 2.97; CI 95%= 1.30 to 4.64; p<0.001). It was negatively affected by the side effects of the drug (b= -3.07; CI 95%= -4.90 to -1.24; p= 0.001), distance to health service (b= -1.86; CI 95%= -3.61 to -0.11; p= 0.037), and tenure (b= -2.16; CI 95%= -3.95 to -0.38; p= 0.017). Adherence to anti tuberculosis treatment was indirectly affected by income, knowledge, and role of drug treatment supervisor. Conclusion: Adherence to anti tuberculosis treatment is directly and positively affected by age, gender, education, income, knowledge, the role of drug taking supervisor, drug availability, and family support. It is negatively affected by the side effects of the drug, distance to health service, and tenure. Keywords : treatment adherence, tuberculosis, determinants, path analysis Correspondence: Surahman Hamidi. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java. Email: surahmanhamidi@student.uns.ac.id. Mobile: 085267­456713. Journal of Epidemiology and Public Health (2019), 4(3): 205-214 https://doi.org/10.26911/jepublichealth.2019.04.03.08

Telfairia occidentalis (Cucurbitaceae) pulp extract mitigates rifampicin-isoniazid-induced hepatotoxicity in an in vivo rat model of oxidative stress

ObjectiveDrug-induced liver injury complicates antituberculosis drug treatment and is a leading cause of death worldwide. The aim of this study is to establish the ethnomedicinal claim of hepatoprotective effects of fruit pulp extract of Telfairia occidentalis against rifampicin (RIF) and isoniazid (INH)-induced oxidative stress in rats. MethodsT. occidentalis pulp extract (TOPE) (125–500 mg/kg) and silymarin (50 mg/kg) were evaluated in an induced hepatotoxicity model of oxidative stress in Wistar rats by intoxication with RIF and INH (100 mg/kg each) orally for 60 d. Markers indicating oxidative stress and hepatic damage such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were assessed. Biomarkers of antioxidant status, including catalase, glutathione reductase, glutathione peroxidase and superoxide dismutase, and marker of lipid peroxidation, malondialdehyde (MDA), were assayed using standard procedures. The hematological profile, lipid profile, serum markers for kidney function and histopathological examination were also assessed. ResultsIntoxication with RIF and INH markedly reduced the hematological indices and elevated the biochemical enzyme markers (AST, ALT and ALP, P < 0.001) and lipid profile (P < 0.001), while antioxidant biomarkers were significantly (P < 0.01) depressed and MDA was elevated. However, pretreatment with TOPE significantly (P < 0.001) alleviated this alteration and sustained the antioxidant potentials. The histopathological morphology supports the biochemical evidence of hepatoprotection. ConclusionCurrent study is indicative of potential antioxidant activity, hepatoprotective effects and plausible therapeutic alleviation of RIF-INH-induced hepatotoxicity of TOPE in laboratory animals.

Changes of CRP serum levels in pulmonary TB patients with AFB smear-positive sputum before and two months after receiving anti-tuberculosis drug treatment

BackgroundPulmonary tuberculosis (TB) produces an inflammatory process of the lung parenchyma. While effective treatment of pulmonary TB and disease resolution processes have an impact on decreasing inflammatory conditions of the pulmonary parenchyma. This stimulates researchers to investigate changes in lung parenchymal inflammatory conditions detected from changes of C-reactive protein (CRP) serum levels pre and post two months of anti-tuberculosis drug treatment. ObjectivesTo know the changes of CRP serum levels in pulmonary TB patients with Acid Fast Bacillus (AFB) smear-positive sputum before and 2 months after receiving anti-tuberculosis drug treatment. MethodThis study used prospective cohort study design, conducted in pulmonary outpatient unit at Dr. Soetomo General Hospital Surabaya from March to June 2013. Sample size was 30 pulmonary TB patients with AFB smear-positive sputum. AFB sputum grading and CRP serum level was measured before and 2 months after receiving anti-tuberculosis drug treatment. International Union Against Tuberculosis and Lung Disease (IUATLD) scale was used for AFB sputum grading. CRP serum was measured using immunoturbidimetric method. ResultThe average CRP serum levels of pre anti-tuberculosis drug treatment were 6.48 ± 4.27 mg/dL in males and 6.28 ± 5.26 mg/dL in females. After two months of anti-tuberculosis drug treatment, the average CRP serum levels were 1.21 ± 1.94 mg/dL in males and 1.21 ± 1.22 mg/dL in females. Sputum conversion occurred in 27 out of 30 samples after two months of anti-tuberculosis drug treatment. ConclusionThe CRP serum levels was not significantly different in patients with pulmonary TB who experienced sputum conversion compared to patients without sputum conversion after two months of anti-tuberculosis drug treatment.

Anti-tuberculosis drug concentrations and treatment outcomes among HIV-infected patients with tuberculosis

Anti-tuberculosis drug concentrations and treatment outcomes among HIV-infected patients with tuberculosis

Clinical analysis of 9 children with vertical infection of tuberculosis

Objective To explore the risk, diagnosis, treatment and prognosis of newborns suffering from congenital latent tuberculosis infection (CLTBI) by vertical transfer of mycobacterium tuberculosis(VTRTB) from mothers with active tuberculosis (TB) mothers during pregnancy. Methods The clinical data of 7 children with CLTBI follow-up of 1-6 years in Children′s Hospital of Nanjing Medical University and 2 cases from literatures were reviewed, and they were divided into simple CLTBI group(n=5) and active TB group (n=4). Combined with the maternal history, the epidemiology, clinical features, treatment, prognosis and relative factors of the children were analyzed. Results Eight mothers had active TB during pregnancy, and premature delivery rate and low birth weight rate were 55.56%(5/9 cases) respectively.The positive conversion rates of purified protein derivative tests (PPD), acid-fast bacilli (AFB) and TB culture were 6/9 cases, 0/9 cases and 1/9 cases, respectively.Positive results of T cell enzyme-linked immunospot tuberculous test (T-SPOT.TB) and TB-DNA by fluorescent quantitative polymerase chain reaction (FQ-TB-DNA) were detected in 4 cases respectively, 1 of 3 patients with T-SPOT.TB and 1 of 3 patients with FQ-TB-DNA were positive.There were 5 cases with chemoprophylaxis of anti-TB drugs for 1-6 years with isonicid or rifampicin; 3 cases with pulmonary hilar or mediastinal lymph nodes enlargement, and 3 cases with pulmonary diffuse punctate, nodular or patchy high density shadow in 3 cases; the rate of VTRTB in 9 cases was 8/9 (88.89%) based on laboratory examination of etiology and immunology, and the risk of active TB in infants and early childhood was close to 50% in neonates with CLTBI; the incidence of active TB was reduced from 100%(4/4 cases) of non-intervention down to 0(0/5 case) of intervention. Conclusions Etiology, immunology, imaging examination of TB and clinical efficacy, can prompt active TB and retrospective diagnosis of CLTBI, and application of T-SPOT.TB and FQ-TB-DNA for early diagnosis of CLTBI has a higher applied value; prophylactic and treatment of anti-tuberculosis drugs can reduce the progression of CLTBI to active TB and improve outcomes. Key words: Infant, newborn; Latent tuberculosis infection; Tuberculin test; Vertical transmission

Serum Macrophage Migration Inhibitory Factor as a Biomarker of Active Pulmonary Tuberculosis.

BackgroundMacrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine with chemokine-like functions, has been shown to play a central role in several acute and chronic inflammatory diseases. However, limited information is available regarding the use of MIF as an inflammatory pathway marker in patients with tuberculosis. This study aimed to investigate the association of MIF with IFN-γ and TNF-α in active pulmonary tuberculosis (APTB) following anti-tuberculosis treatment.MethodsThe MIF, TNF-α, and IFN-γ serum levels were determined in 47 patients with APTB by cytokine-specific ELISA at four phases: prior to anti-tuberculosis drug treatment (baseline), and following 2, 4, and 6 months of treatment. In addition, we measured the MIF, TNF-α, and IFN-γ serum levels in 50 health controls.ResultsMIF serum levels were significantly elevated (P<0.05) in patients with APTB prior to treatment compared with that in control subjects, and TNF-α ≥449.7 pg/mL was associated with high MIF levels (≥13.1 ng/mL). MIF levels were significantly reduced (P<0.01) following 2, 4, and 6 months of treatment, with variations in TNF-α and IFN-γ serum levels. MIF levels were positively correlated with the paired TNF-α level at baseline (r=0.1103, P=0.0316) and following 6 months of treatment (r=0.09569, P=0.0364).ConclusionsA reduction in the MIF serum levels in patients with APTB following anti-tuberculosis treatment may positively affect host immune protection against Mycobacterium tuberculosis infection. Thus, serum MIF levels may constitute a useful marker for assessing therapy effectiveness in patients with APTB.