Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats / Efeitos de Solanum lycopersicum L. (tomate) contra hepatotoxicidade induzida por isoniazida e rifampicina em ratos albinos wistar

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats

Abstract Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferronis post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

Resumo As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

Dodecanoic acid & palmitic acid disarms rifampicin resistance by putatively targeting mycobacterial efflux pump Rv1218c

Background & objectives: Drug-resistant tuberculosis (TB) jeopardizes the treatment process with poor outcomes. Efflux pumps (EPs) belonging to the ABC transporter family in Mycobacterium tuberculosis confer resistance to rifampicin (RMP) besides genetic mutations thus serving as a target for a potential adjunct therapeutic inhibitory molecule. Rv1218c is one such pump that was previously reported to be active in multidrug-resistant TB clinical isolates. Methods: In this study, the inhibition potential of Rv1218c-EP was tested on 8 molecules that were shortlisted by in silico methods. These molecules were subjected to the minimum inhibitory concentration (MIC) determination, checkerboard drug combination assay, ethidium bromide-DNA binding assay, and in vitro and ex vivo cytotoxicity assay. Results: Based on the outcome of the study, two molecules dodecanoic acid (DA) and palmitic acid (PA) were found to be potential enough to decrease the MIC of RMP by 8 to 1000 folds against multidrug-resistant clinical isolates and Rv1218c expressing recombinant Mycobacterium smegmatis. Interpretation & conclusions: These molecules were also found to reduce the time taken by RMP to kill these drug-resistant Mycobacteria to 48 h, unlike control isolates that survived more than 240 h of RMP exposure. The functional concentration of both molecules was non-toxic to the epithelial and blood mononuclear cells. With further comprehensive scientific validation, PA and DA could be recommended as adjunct therapeutic molecules with first-line anti-TB drugs to treat drug-resistant TB.

Diagnostic efficacy of joint detection of Xpert MTBRIF, TB-RNA and TB-DNA in bronchoalveolar lavage fluid for smear-negative pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To investigate the diagnostic value of joint detection of Mycobacterium tuberculosis rifampicin resistance gene (Xpert MTB/RIF), Mycobacterium tuberculosis ribonucleic acid (TB-RNA) and Mycobacterium tuberculosis deoxyribonucleic acid (TB-DNA) in bronchoalveolar lavage fluid for smear-negative pulmonary tuberculosis. Methods A total of 806 patients with suspected smear-negative pulmonary tuberculosis admitted to our hospital from May 2020 to July 2022 were selected, 506 patients diagnosed as bacterial negative pulmonary tuberculosis by clinical, X-ray and sputum samples were classified as bacterial negative pulmonary tuberculosis group, and the other 300 patients with non-tuberculous pulmonary disease were classified as non-tuberculous pulmonary disease group. XpertMTB/RIF, TB-RNA and TB-DNA in bronchoalveolar lavage fluid of all patients were detected. With clinical, X-ray and sputum specimen examination of mycobacterium tuberculosis as the gold standard, the diagnostic efficacy of alveolar lavage solution Xpert MTB/RIF, TB-RNA and TB-DNA alone and in combination was analyzed. Results The positive detection rates of Xpert MTB/RIF, TB-RNA and TB-DNA in bronchoalveolar lavage fluid of the smear-negative pulmonary tuberculosis group and the non-tuberculosis pulmonary disease group were 69.96% (354/506) and 2.67% (8/300), 61.46% (311/506) and 5.00% (15/300), and 63.64% (322/506) and 8.00% (24/300), respectively. The rates in the smear-negative pulmonary tuberculosis group were higher than those in the non-tuberculosis lung disease group, and the differences were statistically significant (χ2=342.005, 246.930, 235.687, P<0.01). Compared with the gold standard, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of Xpert MTB/RIF in the diagnosis of smear-negative pulmonary tuberculosis were 69.96%, 97.33%, 80.15%, 97.79% and 65.77%, respectively; those values of TB-RNA were 61.46%, 95.00%, 73.95%, 95.40% and 59.38%, respectively; those values of TB-DNA were 63.64%, 92.00%, 74.19%, 93.06% and 60.00%, respectively; those values of combined diagnosis with Xpert MTB/RIF, TB-RNA and TB-DNA were 61.26%, 100.00%, 75.68%, 100.00% and 60.48%, respectively; the specificity and positive predictive value of combined detection were higher than those of single detection (P<0.05). Conclusions The joint detection of Xpert MTB/RIF, TB-RNA and TB-DNA in bronchoalveolar lavage fluid can improve the diagnostic efficacy of smear-negative pulmonary tuberculosis and is worthy of clinical promotion and application.

Construction of a High-Throughput Mutation Library of Mycobacterium Rifampin Resistance Gene rpoB / 中山大学学报(医学科学版)

ObjectiveTo establish a mutation library of rifampicin resistance gene rpoB. MethodsThe ΔrpoB attB：：rpoB strain of Mycobacterium smegmatis （M. smegmatis） be constructed by homologous recombination and L5 attB phage integration site exchange. Based on the L5 attB plasmid exchange system and resistance selection medium， 48 clones are selected to verify plasmid replacement efficiency. Degenerate primers are designed every 3 bases in the rifampicin resistance determining region （RRDR）， and a full-coverage mutation library of 81 bases in RRDR region is obtained by PCR amplification. The library fragments are seamlessly cloned into the vector and transformed into Escherichia coli （E. coli）to form an E. coli mutation library. Based on the principle of plasmid exchange， the mutant plasmid library is transformed into the M. smegmatis strain ΔrpoB attB：：rpoB， and the original L5 attB site plasmid is replaced to form the M. smegmatis mutant library. The genotype of the library are determined by genome extraction， library construction and high-throughput sequencing. ResultsCompared with the wild-type rpoB gene （5 600 bp）， the amplified fragment of the rpoB knockout strain is 2 200 bp， which proved that the ΔrpoB attB：：rpoB conditional knockout strain of M. smegmatis is successfully constructed. The success rate of plasmid replacement is 100%. There were 540 kinds of single amino acid mutations in both E. coli library and M. smegmatis library， 5 301 kinds of multi-point mutations in E. coli library， and 853 kinds of multi-point mutations in M. smegmatis library. The correlation coefficient between E. coli library and M. smegmatis library is 0.84. ConclusionsWe have developed a strategy to construct a library of mutants targeting the essential mycobacterial gene rpoB， and successfully established a mutant library of rifampicin resistance gene rpoB.

Father-Daughter Duo: How Unmasking Leprosy in Father Helped in Leprosy Diagnosis in the Daughter - A Case Report

In highly endemic countries like India, where tuberculosis (TB) and leprosy infection may coexist, screening the other disease before initiating treatment is important to prevent Rifampicin resistance since both diseases are treated with and sensitive to Rifampicin. Here, we report a leprosy case involving the unmasking of leprosy in a treated patient with Pulmonary TB. In this case, a high index of suspicion of Erythema Nodosum Leprosum (ENL) in a patient with no history of leprosy disease or treatment with anti-leprosy drugs was observed. He, however, had a history of taking anti-tuberculous medicine 1.5 years earlier. This case report also acknowledges the physician’s prompt referral of this patient to a dermatologist. Taking a detailed family history and screening helped us diagnose leprosy in the patient’s daughter. It also emphasises the atypical presentation of leprosy, which (although described in textbooks) is being reported here.

Vigilancia de la resistencia del Mycobacterium tuberculosis a los fármacos en Paraguay, 2014 a 2017 / Surveillance of drug resistance of Mycobacterium tuberculosis in Paraguay, 2014 to 2017

El objetivo del estudio fue identificar la resistencia del Mycobacterium tuberculosis a los fármacos en Paraguay, 2014 a 2017. Se realizó un estudio observacional retrospectivo. Se utilizaron los datos del Programa Nacional de Tuberculosis del Paraguay comprendidos entre los años 2014 a 2017. Se incluyeron todos los pacientes con diagnóstico de Tuberculosis que se realizaron un test de resistencia. Se extrajeron los datos en Excel y fueron analizados con Stata 17.0. Se incluyeron 3429 pacientes con tuberculosis que contaban con resultado de al menos una prueba de sensibilidad. La resistencia se encontró en 2.1% de los pacientes. La resistencia a la Rifampicina estuvo presente en el 0.3% de los casos mientras que a la Izionazida en el 0.6% de los casos. La prevalencia de resistencia fue más alta en hombres 3.4 (IC 95% 2.2 - 4.8) p=0.003, que residían en el chaco 6.0 (IC 95% 3.4 - 9.7) p=0.000, previamente tratados 2.7 (IC 95% 1.1 - 5.1) p=0.010. En el modelo se pudo observar que un paciente previamente tratado tiene mayores posibilidades de tener resistencia OR 2.62 (IC 95% 1.1 - 6.24). La prevalencia de resistencia del Mycobacterium tuberculosis a fármacos estuvo relacionada con haber sido previamente tratado

The objective of the study was to identify the resistance of Mycobacterium tuberculosis to drugs in Paraguay, 2014 to 2017. A retrospective observational study was carried out. The data from the National Tuberculosis Program of Paraguay between the years 2014 to 2017 were used. All patients with a diagnosis of Tuberculosis who underwent a resistance test were included. Data were extracted in Excel and analyzed with Stata 17.0. 3429 tuberculosis patients who had a result of at least one sensitivity test were included. Resistance was found in 2.1% of patients. Resistance to Rifampicin was present in 0.3% of cases while to Izionazide in 0.6% of cases. The prevalence of resistance was higher in men 3.4 (95% CI 2.2 - 4.8) p = 0.003, who resided in the Chaco 6.0 (95% CI 3.4 - 9.7) p = 0.000, previously treated 2.7 (95% CI 1.1 - 5.1) p = 0.010. In the model, it was observed that a previously treated patient has a greater chance of having resistance OR 2.62 (95% CI 1.1 - 6.24). The prevalence of resistance of Mycobacterium tuberculosis to drugs was related to having been previously treated

ISOLATION IDENTIFICATION AND PATTERNS OF ANTI-TUBERCULOSIS DRUG RESISTANCE FROM TERTIARY CARE HOSPITAL UDAIPUR (RAJASTHAN)

Objective: Resistance against Mycobacterium tuberculosis (MTB) is important in the sense that it has an implication in the control of tuberculosis. The terms used to describe resistance to antituberculosis drugs are resistance among new cases (or primary resistance) and resistance among previously treated patients. The resistance among previously treated patients may be due to faulty treatment like prescription of inadequate treatment regimens, interrupted availability or poor quality of drugs, or incomplete treatment adherence while subsequent transmission of these resistant organisms to others will lead to development of disease which is resistant from the beginning called primary resistance. Pakistan is ranked eighth in terms of global estimated burden of tuberculosis cases. Multi-Drug Resistant (MDR) tuberculosis among new cases and MDR among previously treated patients is 3.2% and 35% respectively. Material and methods: - AFB smear examination and grading: - AFB smear examination was carried out by direct microscopy using the Ziehl Neelsen (ZN) method. Sputum smear result was examined and interpreted according to the AFB grading. AFB culture and drug susceptibility test: - Culture examinations were done on all diagnostic specimens of AFB smear positivity. Sputum specimens from each patient were processed with sodium hydroxide (NaOH) method-Modi?ed Petroff 's procedure and cultured on Lowenstein-Jensen (LJ) slopes.10 All inoculated LJ drug and control media were incubated at 37ºC. All cultures were examined 48-72 hours after inoculation to detect gross contaminants. Thereafter, cultures were examined weekly, up to eight weeks on a speci?ed day of the week. Typical colonies of M. tuberculosis were rough, crumbly, waxy, non-pigmented (buff coloured) and slow-growers, i.e., only appeared two to three weeks after inoculation. The colony was con?rmed by ZN staining. Detection time for MOTT was 25 days. M. tuberculosis positive strains were culture negative when they grew on p-nitro benzoate (PNB) containing medium. Only a few colonies of non-tuberculosis Mycobacteria (NTM – often pigmented, with smooth morphology or PNB positive) were grown as visible colonies on PNB containing medium. Anti-TB drug susceptibility testing: - anti-susceptibility testing perform on pre-formed LJ media with antitubercular drugs Tuberculosis First Line Kit (Total 7 slants) Containing ?ve antitubercular agent (Isoniazid, Streptomycin, Ethambutol, Rifampicin and Pyrazinamide) 2 controls without any antimicrobial agent. Results: out of 119 samples antitubercular testing against ?rst line antitubercular drugs such as Pyrazinamide were shows 12 (10.08%) sample were resistance which accounts maximum resistance among ?rst line antitubercular another ?rst line antitubercular drugs shows resistance as follows Streptomycin (9.24%), Ethambutol (8.40%), Isoniazid (7.56%), Rifampicin (6.72%), drugs out of 119 samples in which 107 samples were susceptible to the Pyrazinamide drug in in-vitro antitubercular susceptibility testing. Antitubercular resistance against second line antitubercular drugs were shows as follows out of 119 samples antitubercular testing Ethionamide were shows 9 (8.18%) sample were resistance which accounts maximum resistance among second line antitubercular another second line antitubercular drugs shows resistance as follows Clarithromycin (6.72%), Cipro?oxacin (5.88%), D- Cycloserine (5.88%), Amikacin (5.04%), Kanamycin (4.20%), P- aminosalicylic acid ( 4.20%) and Rifabutin (3.36%) drugs out of 119 samples in which 107 samples were susceptible to the Pyrazinamide drug in in-vitro antitubercular susceptibility testing. MDR-TB emerged in patients who were resistant to Rifampicin and Isoniazide was 6 in number during this study.

Rifampicin-induced thrombocytopenia in a patient of disseminated tuberculosis

Thrombocytopenia may be associated with a variety of conditions and risks depending on its severity, ranging from mild epistaxis to life-threatening bleeding. Many drugs or herbal remedies can cause thrombocytopenia by either inhibiting platelet production and/or enhancing their destruction from the peripheral blood-mediated through an immunological mechanism implicating drug-dependent antibodies. Drugs are a common cause of acute immune-mediated thrombocytopenia in adults, the drug etiology is often initially unrecognized. Most cases of drug-induced thrombocytopenia are caused by drug-dependent antibodies that are specific for the drug structure and bind tightly to platelets by their Fab regions but only in the presence of the drug. Thrombocytopenia is an uncommon but life-threatening complication of certain antitubercular drugs. The discovery of isolated thrombocytopenia in a patient taking several medications presents a challenging clinical problem. We report a case of a young immunocompetent female who presented with disseminated tuberculosis and was found to have rifampicin-induced thrombocytopenia

Statistical analysis of 484 Mycobacterium tuberculosis genomes reveals an association between single nucleotide polymorphisms on ponA1 gene and LAM and Haarlem lineages / Análisis estadístico de 484 genomas de Mycobacterium tuberculosis revela una asociación entre los polimorfismos de un solo nucleótido en el gen ponA1 y los linajes LAM y Haarlem

Abstract Objectives: Evaluate the association between rifampicin resistance and the presence of at least one SNP in the rpoB and ponA1 genes and the spoligotype defined lineages. Material and Methods: This study analyzed two databases of 484 genomes of M. tuberculosis from strains isolated from patients in the cities of Lima and Callao, for which the odds ratio (OR) was calculated considering belonging to a certain spoligotype defined lineages as an exposure factor. Results: No statistically significant association (ρ value> 0.05) was found between the presence of at least one SNP in the rpoB gene and the lineages included in the study (LAM, Haarlem, T and Beijing). However, a statistically significant association was found between the presence of at least one SNP in the ponA1 gene and the LAM and Haarlem lineages (ρ value <0.05). An association was found between the P631S SNP in the ponA1 gene and the LAM and Haarlem lineages; and the A516T SNP, of this same gene, presented an association with the LAM lineage. Likewise, an association was found between rifampicin resistance and the LAM lineage. Conclusions: The presence of SNPs in the ponA1 gene is associated with the LAM and Haarlem lineages.

Resumen Objetivos: Evaluar la asociación entre la resistencia a rifampicina y la presencia de al menos un SNP en los genes rpoB y ponA1 y los linajes definidos por espoli gotipos. Material y Métodos: Este estudio analizó dos bases de datos de 484 genomas de M. tuberculosis de cepas aisladas de pacientes de las ciudades de Lima y Callao, para lo cual se calculó el odds ratio (OR) considerando la pertenencia a determinado linaje definido por espoligotipos como un factor de exposición. Resultados: No se encontró una asociación estadísticamente significativa (valor de ρ >0.05) entre la presencia de al menos un SNP en el gen rpoB y los linajes incluidos en el estudio (LAM, Haarlem, T y Beijing). No obstante, se halló una asociación estadísticamente significativa entre la presencia de al menos un SNP en el gen ponA1 y los linajes LAM y Haarlem (valor de ρ <0.05). Se encontró una asociación entre el SNP P631S del gen ponA1 y los linajes LAM y Haarlem; y el SNP A516T, de este mismo gen, presentó una asociación con el linaje LAM. Asimismo, se halló una asociación entre la resistencia a rifampicina y el linaje LAM. Conclusiones: La presencia de SNPs en el gen ponA1 está asociada con los linajes LAM y Haarlem.

Pharmaceutical care for patient with schizophrenia combined with pulmonary tuberculosis： a case report / 四川精神卫生

This paper reported a case of schizophrenia combined with pulmonary tuberculosis treated with clozapine in combination with rifampicin. Due to the induction of hepatic drug enzyme of rifampicin， plasma concentration of clozapine could not reach the effective concentration and the patient still had psychotic symptoms such as persecutory delusion. After discontinuation of rifampicin， plasma concentration of clozapine were in the effective concentration range and the patient's psychiatric symptoms improved. By analysing the therapeutic regimen for the patient with schizophrenia combined with pulmonary tuberculosis， this case suggested a possible interaction between clozapine and rifampin， and provided a reference for the treatment of this type of patients.

Detection and factors associated with tuberculosis and rifampicin resistance among presumptive patients at the Thailand-Myanmar border

@#Tuberculosis (TB) continues to be a major public health problem in Thailand and many countries. Endemic TB and outbreaks of TB drug resistance in the borderlands are particularly important. The Thailand-Myanmar border has extensive cross-border travel that may accelerate TB’s spread. This cross-sectional study aimed to determine the frequency and factors associated with TB, and rifampicinresistant TB (RR-TB) among presumptive tuberculosis patients in Mae Sot Hospital. Sputum was processed by microscopic examination and Xpert MTB/RIF assay. Laboratory results and socio-demographic characteristics were collected and analyzed. Univariate and multivariate analyses were performed to assess the association of the risk factors with TB and RR-TB. The significant variables at p-values < 0.05 in univariate analysis were selected for multivariate analysis. Of 365 presumptive patients enrolled, 244 (66.85%) were males and 199 (54.52%) were Burmese. Of these, 314 (86.03%) were registered as new cases and 183 (50.14%) worked as laborers. Sputum microscopy was positive in 132 (36.16%) cases. Based on Xpert MTB/RIF, the frequency of TB was 136 (37.26%) and RR-TB was 15 (11.03%). TB was more common in males than females. The majority of the cases belonged to the 26-50-year-old age group and migrant workers. In RR-TB detection, the rpoB mutations covered by probe E were the most frequently observed. Sequencing showed that the most highly mutated codon was codon 531 and Ser531Thr was the most common mutation. For risk factor analysis, working as laborers was significantly (p-value < 0.05) associated with TB (aOR 2.83; 95% CI 1.43-5.63) and previously treated cases were significantly associated with RR-TB (aOR 12.33; 95% CI 2.29-66.49). The high frequency of TB and RR-TB in migrants highlights the problem and factors associated with TB at the border and the need for efforts in TB control programs in this setting.

Mycobacterium tuberculosis en muestras de pacientes pulmonares y extrapulmonares del Hospital Vicente Corral Moscoso / Mycobacterium tuberculosis in pulmonary and extrapulmonary patient samples from Vicente Corral Moscoso Hospital / Mycobacterium tuberculosis em amostras de pacientes pulmonares e extrapulmonares no Hospital Vicente Corral Moscoso

La tuberculosis es una enfermedad infecciosa causada por la bacteria Mycobacterium tuberculosis cuya prevalencia a nivel mundial lejos de disminuir cada vez cobra un número mayor de morbimortalidad aunado al incremento de la resistencia bacteriana. OBJETIVOS: caracterizar la infección por Mycobacterium tuberculosis con las variables de estudio que presentan mayor asociación con la enfermedad: tipo de muestra, sexo biológico, origen, grupo etario, área hospitalaria, susceptibilidad a rifampicina y tipo de diagnóstico. MATERIALES Y MÉTODOS: estudio con enfoque cuantitativo descriptivo, documental, cuya muestra estuvo conformada por 62 aislados clínicos de Mycobacterium tuberculosis procesadas por baciloscopia, cultivo y técnicas moleculares, Hospital Vicente Corral Moscoso durante el periodo 2019-2020. RESULTADOS: Mycobacterium tuberculosis fue más prevalente en el grupo de adultos representando el 71%, con una edad media de 47 años, predomina el sexo masculino con 75.8%, el área hospitalaria de mayor ingreso fue emergencia con 66.13%, con muestras de origen pulmonar 88.71%. Los pacientes que presentaron coinfección de tuberculosis a VIH fueron de 11.29%. El método diagnóstico más empleado fue baciloscopia con cultivo representado el 41.9%. La presencia de resistencia a rifampicina correspondiente a 13% en muestras pulmonares como extrapulmonares. CONCLUSIONES: la tuberculosis es una enfermedad infectocontagiosa que se caracteriza por el periodo de latencia prolongado entre la infección inicial y las manifestaciones clínicas, pudiendo ser transmitido por las vías directa o indirecta. Sus altas tasas de morbimortalidad son elevadas en grupos poblacionales adultos prioritariamente del sexo masculino aunado a serie de factores de base como el tabaquismo.

Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis whose worldwide prevalence, far from decreasing, is increasing its morbimortality, together with the increase of bacterial resistance. OBJECTIVES: to characterize Mycobacterium tuberculosis infection with the study variables that are most associated with the disease: type of sample, biological sex, origin, age group, hospital area, susceptibility to rifampicin and type of diagnosis. MATERIALS AND METHODS: a quantitative descriptive, documentary approach study, whose sample consisted of 62 clinical isolates of Mycobacterium tuberculosis processed by smear microscopy, culture and molecular techniques, Vicente Corral Moscoso Hospital during the period 2019-2020. RESULTS: Mycobacterium tuberculosis was more prevalent in the adult group representing 71%, with a mean age of 47 years, male sex predominates with 75.8%, the hospital area of greatest admission was emergency with 66.13%, with samples of pulmonary origin 88.71%. The number of patients with tuberculosis/HIV coinfection was 11.29%. The most commonly used diagnostic method was smear microscopy with culture, representing 41.9%. The presence of rifampicin resistance corresponded to 13% in pulmonary and extrapulmonary samples. CONCLUSIONS: tuberculosis is an infectious disease characterized by a long latency period between the initial infection and clinical manifestations, and can be transmitted by direct or indirect routes. Its high morbimortality rates are elevated in adult population groups, mainly males, together with a series of underlying factors such as smoking.

A tuberculose é uma doença infecciosa causada pela bactéria Mycobacterium tuberculosis, cuja prevalência mundial, longe de diminuir, está aumentando em morbidade e mortalidade, juntamente com o aumento da resistência bacteriana. OBJETIVO: para caracterizar a infecção por Mycobacterium tuberculosis com as variáveis de estudo mais associadas à doença: tipo de amostra, sexo biológico, origem, faixa etária, área hospitalar, suscetibilidade à rifampicina e tipo de diagnóstico. MATERIAIS E MÉTODOS: um estudo descritivo quantitativo, documental, cuja amostra consistiu de 62 isolados clínicos de Mycobacterium tuberculosis processados por microscopia de esfregaço, cultura e técnicas moleculares, Hospital Vicente Corral Moscoso durante o período de 2019-2020. RESULTADOS: Mycobacterium tuberculosis foi mais prevalente no grupo adulto representando 71%, com uma idade média de 47 anos, predominantemente masculina com 75,8%, a área hospitalar de maior internação foi de emergência com 66,13%, com amostras de origem pulmonar 88,71%. O número de pacientes com co-infecção TB/HIV foi de 11,29%. O método de diagnóstico mais freqüentemente utilizado foi a microscopia de esfregaço com cultura, representando 41,9%. A presença de resistência à rifampicina correspondeu a 13% tanto em amostras pulmonares quanto extrapulmonares. CONCLUSÕES: a tuberculose é uma doença infecciosa caracterizada por um período prolongado de latência entre a infecção inicial e manifestações clínicas, e pode ser transmitida por vias diretas ou indiretas. Suas altas taxas de morbidade e mortalidade são altas em grupos da população adulta, principalmente homens, juntamente com uma série de fatores subjacentes, como o tabagismo.

Quality analysis of some drugs against tuberculosis an in vitro study / Монголын эм зүй, эм судлал

Introduction@#According to the statistical data of 2019, 10 million people in 202 countries have been registered as tuberculosis cases, 1.6 million people has died around the world. In 2019, 4,089 new tuberculosis cases were determined, of which 265 died in Mongolia.@*Purpose@#The purpose of this study is analyze quality of some drugs used in the treatment of certain groups of tuberculosis in accordance with international standards.@*Materials and methods@#Isoniazid 300 mg, Rifampicin 150 mg, Pyrazinamide 400 mg and Ethambutol 400 mg, which are commonly used in Mongolia, were analyzed according to the pharmacopoeia methods of United States, Chinese and British.@*Results@#Appearance - Complies with the requirements of the certificate for sensory examination. Identification - It was determined by an infrared spectrophotometry. Average weight - Isoniazid 547.5 mg, Rifampicin 277.6 mg, Pyrazinamide 640.8 mg, Etambutol 399.6 mg. DisintegrationIsoniazid decomposes in 2.5 minutes, Pyrazinamide decomposes in 4.6 minutes, Etambutol decomposes in 8.5 minutes. Friability – Isoniazid - 0.4%, Pyrazinamide 10.4%, Hardness – Isoniazid 0.4%, Pyrazinamide is - 49.7 N, Dissolution – Isoniazid not less than - 95.7%, Rifampicin - 78.7%, Pyrazinamide - 95.7%, Assay - Etambutol is - 399.6 mg, Rifampicin is 139.94 mg, Isoniazid is - 293.6 mg Pyrazinamide - 492.5 mg complied with the standard requirements. @*Conclusion@#Analysis of tuberculosis drugs quality by pharmacopoeia methods including its appearance, identification, average weight, friability, hardness, disintegration, dissolution and assay, the isoniazid 300 mg tablets are complied with the United States pharmacopoeia, Rifampicin 150 mg tablets met British pharmacopoeia, and Ethambutol 400 mg tablets are complied with Chinese pharmacopoeia. Pyrazinamide 400 mg tablets did not complies the friability requirements of the United States Pharmacopoeia and also satisfied with the other requirements.

Prediction of the bioequivalence of different crystal forms of rifampicin based on physiologically based pharmacokinetic model / 中国药科大学学报

@#The physiologically based pharmacokinetic (PBPK) modeling strategy was adopted to predict the pharmacokinetic behavior of crystal forms I and II of rifampicin in humans, which was used to determine whether the two were bioequivalent.After conducting studies in vitro of the two crystal forms, a rat PBPK model was established based on the pharmacokinetic data of intravenous administration in rats.The model was optimized by the pharmacokinetic data of oral administration in rats.Species were extrapolated to healthy humans, and the extrapolation model was used to predict such pharmacokinetic behaviors as the drug-time curve, absorption site, and absorption amount of the two crystal forms of rifampicin in healthy humans.The prediction results of the healthy human model showed that the cmax of form I and form II rifampicin were 8.42 and 10.35 μg/mL, tmax were 0.40 and 0.32 h,and AUC0-t were both 62.90 μg·h/mL.According to the prediction results of absorption, neither crystal form I nor crystal form II rifampicin was absorbed in the stomach, yet both were completely absorbed in the intestinal tract, with both the absorption site and the absorption amount were basically the same.The pharmacokinetic parameters of both crystal forms I and II of rifampicin were very close, which could indicate bioequivalence.

Improving access to quality of care for drug-resistant tuberculosis patients: a qualitative study on patient-centered support system / 中华医院管理杂志

Objective:To analyze the role of patient support system in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment adherence and outcome, and provide evidence for deepening the patient-centered support system.Methods:Based on the stakeholder analysis, definite stakeholders (administrators from the Department of Medical Insurance, and those from the provincial CDC), expectant stakeholders (administrators from regional CDC, health workers from primary CDCs, medical workers from designated MDR/RR-TB hospitals and MDR/RR-TB patients), and latent stakeholders (MDR/RR-TB patient families and their neighbors or colleagues) were selected using a purposive sampling. These stakeholders were subject to a semi-structured interview on patient support. The inclusion of participants ceased after reaching code or thematic saturation and meaning saturation, while thematic framework analysis was applied in interview data.Results:The 25 interviewees included could be categorized into three groups of stakeholders, i. e., 4 definite stakeholders, 19 expectant stakeholders and 2 latent stakeholders. Three themes summarized in this regard were definite stakeholders providing policy support to advance these patients′ access to standardized diagnosis and treatment services; diagnosis and treatment and management support of expectant stakeholders of these patients to encourage their compliance to treatment and enable their access to high quality medical care; and support from latent stakeholders as a critical guarantee for the patients to welcome a desirable treatment outcome. Psychological support provided under MDR/RR-TB basic care program in some provinces contributed positively to raising patients′ compliance. Economic support, treatment support from family menmbers ccould help the patients to welcome desirable outcomes.Conclusions:MDR/RR-TB patient-centered support system operating in the Yangtze River delta provide the patients with MDR/RR-TB diagnostic and treatment services of some accessibility. Given the progress, there are still shortcomings for the respective stakeholders to enhance their attention and collaboration to improve the access and equity to medical service.

Resistencia de Mycobacterium tuberculosis a quinolonas y fármacos inyectables en el departamento del Atlántico, 2013-2016 / Resistance of Mycobacterium tuberculosis to quinolone and injectable drugs in Atlántico department, 2013-2016

Introducción: En el departamento del Atlántico los estudios de resistencia del Mycobacterium tuberculosis se han limitado a drogas de segunda línea. Objetivo: Determinar prevalencia de resistencia a amikacina, kanamicina, capreomicina y ofloxacina en casos de tuberculosis resistente a isoniacida, rifampicina o a ambas drogas, en el periodo 2013 a 2016 en el departamento del Atlántico. Métodos: Estudio transversal de 194 aislamientos resistentes a isoniacida, rifampicina o ambas, por metodología Genotype MTBDR plus versión 2, enviados al Instituto Nacional de Salud en el periodo 2013 al 2016 para ser confirmados y procesados para drogas de segunda línea. La proporción de resistencia, se hizo según variables sociodemográficas, clínica y de vigilancia en salud pública. Resultados: Las comorbilidades frecuentes encontradas fueron desnutrición con el 18,56 por ciento, seguido de infección concomitante VIH-tuberculosis con el 13,40 por ciento. La ofloxacina en casos no tratados obtuvo la mayor resistencia global con el 1,50 por ciento (IC 95 por ciento 0,18-5,33). En los que fueron previamente tratados la resistencia global a capreomicina fue del 8,10 por ciento (IC 95 por ciento 2,7-17,8). En los resistentes a rifampicina, un caso fue extensivamente resistente y dos casos resistentes en los multidrogorresistente. Conclusiones: Se encontró baja resistencia a fluoroquinolonas y fármacos inyectables en pacientes no tratados resistentes a isoniacida, rifampicina o ambas, que muestra que todavía no constituye un problema mayor en el departamento del Atlántico. Se debe complementar su seguimiento con buen manejo tanto físico como psicológico y un equipo de salud fortalecido que actúe prontamente y ayude a la adherencia del paciente a los tratamientos(AU)

Introduction: In Atlántico department, resistance studies of Mycobacterium tuberculosis have been limited to second-line drugs. Objective: Determine prevalence of resistance to amikacin, kanamycin, capreomycin and ofloxacin in cases of tuberculosis resistant to isoniazid, rifampicin or both, in the period 2013 to 2016 in Atlántico department. Methods: Cross-sectional study of 194 isolations resistant to isoniazid, rifampicin or both, by Genotype MTBDR plus version 2 methodology, that were sent to the National Institute of Health from 2013 to 2016 to be confirmed and processed for second-line drugs. The resistance ratio was made according to sociodemographic, clinical and public health surveillance variables. Results: The common comorbilities found were malnutrition with 18.56 percent, followed by concomitant HIV-tuberculosis infection with 13.40 percent. Ofloxacin in non-treated cases achieved the highest overall resistance with 1.50 percent (95 percent CI 0.18-5.33). In those previously treated, global resistance to capreomycin was 8.10 percent (95 percent CI 2.7-17.8). In the ones resistant to rifampicin, one case was extensively resistant and two cases were resistant in multi-drugs resistant. Conclusions: Low resistance to fluoroquinolones and injectable drugs was found in non-treated patients who were resistant to isoniazid, rifampicin or both, showing that it is not yet a major problem in Atlántico department. Its follow-up should be complemented with good physical and psychological management and a strengthened health team that acts promptly and helps the patient adherence to treatments(AU)

Tuberculosis con resistencia a rifampicina en Chile / Tuberculosis with resistance to rifampicin in Chile

Resumen El éxito de los tratamientos acortados de la tuberculosis se debe a la asociación de fármacos bactericidas y esterilizantes, principalmente Rifampicina e Isoniazida. Cuando la Rifampicina no puede ser utilizada por resistencia, los tratamientos son más prolongados y el éxito en la curación se reduce. La resistencia a Rifampicina frecuentemente se acompaña de resistencia a Isoniazida (Multidrogoresistencia o MDR). La OMS informa que en 2019 se diagnosticaron sólo el 44% de los casos estimados de tuberculosis con resistencia a Rifampicina (se proyectaba 465.000 casos) y se trató sólo al 38% de los casos estimados, quedando una gran proporción de casos sin diagnosticar y sin tratar. En Chile la vigilancia de la susceptibilidad a fármacos de primera línea en cepas de Mycobacterium tuberculosis se efectúa mediante biología molecular desde 2014, observándose un progresivo incremento de casos resistentes a Rifampicina desde 1% (23 casos) para ese año hasta 2,2% (65 casos) en 2019. La mayoría de casos de resistencia a Rifampicina corresponden a resistencia inicial. En casos con resistencia a Rifampicina realizamos estudio de susceptibilidad a fármacos de segunda línea en el laboratorio de referencia nacional. La terapia de TB-MDR tradicional tiene baja eficacia, con abandonos frecuentes por su largo tiempo de terapia y toxicidad. Nuevos tratamientos sin inyectables y el uso de Clofazimina, Fluorquinolonas, Linezolid y Bedaquilina tienen una mejor tasa de curación. Recientemente, el Programa de Control de la Tuberculosis de Chile dispone de esta terapia más eficaz y de menor duración por vía oral con estos fármacos.

The high success rate of shortened Tuberculosis (TB) treatments has been achieved by the association of bactericidal and sterilizing drugs. The main drugs are Rifampicin and Isoniazide. When Rifampicin cannot be used by resistance, the treatment is prolonged and success in healing is significantly reduced. Resistance to Rifampicin is often accompanied by resistance to Isoniazide (Multidrug resistance or MDR). WHO reports that only 44% of estimated TB cases with resistance to Rifampicin were diagnosed in 2019 (465,000 cases projected) and only 38% of estimated cases were treated, with a large proportion of cases remaining undiagnosed and untreated. In Chile, monitoring of susceptibility to first-line drugs is conducted in strains of Mycobacterium tuberculosis by molecular biology since 2014, observing a progressive increase in cases with Rifampicin resistance from 1% for that year (23 cases) to 2.2% in 2019 (65 cases). Most cases of resistance to Rifampicin correspond to cases of initial resistance. In cases with resistance to Rifampicin we carry out susceptibility study to second-line drugs in a national reference laboratory. MDR-TB therapy has low efficacy, with frequent abandonments for its long therapy time and toxicity. New non-injectable treatments and use of Clofazimine, Fluorquinolones, Linezolid and Bedaquiline are achieving a better cure rate. Recently, Chile's TB Control Program has this most effective and shorter-lasting oral therapy with these drugs.

Adverse effects of polychemotherapy for leprosy in 13 years of follow-up at a university hospital

Abstract Leprosy is one of the neglected diseases in the world and Brazil is the second country with more cases. A retrospective study was conducted based on the medical records of 196 leprosy patients diagnosed during the course of 13 years at a university hospital. The aim was to describe the adverse effects of polychemotherapy, as well the most prevalent and most vulnerable populations. In the study, dapsone was the most implicated drug, especially in women, and the risk increased with age. The authors conclude that with this patient profile, greater vigilance should be taken regarding possible adverse effects, especially anemia.

Diagnosis of cutaneous tuberculosis (lymph node scrofuloderma) using the Xpert MTB/RIF® method

Abstract Cutaneous tuberculosis is a rare infection that is difficult to diagnose, because it shows less sensitivity and specificity in classic complementary exams when compared with the pulmonary form. The Xpert MTB/RIF® method offers an early diagnosis that identifies the DNA of Mycobacterium tuberculosis and the main mutations that give the bacterium resistance to rifampicin. The authors present a case of scrofuloderma whose diagnosis was quickly obtained through the secretion of a cervical lesion, allowing an early diagnosis and the initiation of appropriate treatment.