History Of Anti-tuberculosis Treatment Research Articles

Development of tuberculosis treatment decision algorithms in children below 5 years hospitalised with severe acute malnutrition in Zambia and Uganda: a prospective diagnostic cohort study

In children with severe acute malnutrition (SAM) tuberculosis is common, challenging to diagnose, and often fatal. We developed tuberculosis treatment decision algorithms (TDAs) for children under the age of 5 years with SAM. In this prospective diagnostic study, we enrolled and followed up children aged <60 months hospitalised with SAM at three tertiary hospitals in Zambia and Uganda from 4 November 2019 to 20 June 2022. We included children aged 2-59 months with SAM as defined by WHO and hospitalised following the WHO clinical criteria. We excluded children with current or history of antituberculosis treatment within the preceding 3 months. They underwent tuberculosis symptom screening, clinical assessment, chest X-ray, abdominal ultrasound, Xpert MTB/RIF Ultra (Ultra) and culture on respiratory and stool samples with 6 months follow-up. Tuberculosis was retrospectively defined using the 2015 standard case definition for childhood tuberculosis. We used logistic regression to develop diagnostic prediction models for a one-step diagnosis and a two-step screening and diagnostic approaches. We derived scores from models using WHO-recommended thresholds for sensitivity and proposed TDAs. This study is registered with ClinicalTrials.gov, NCT04240990. Of 1906 children hospitalised with SAM during the study period, 1230 were screened, 1152 were eligible and 603 were enrolled. Of the 603 children enrolled-median age 15 (inter-quartile range (IQR): 11-20) months and 65 (11.0%) living with HIV-114 (18.9%) were diagnosed with tuberculosis, including 51 (8.5%) with microbiological confirmation and 104 (17.2%) initiated treatment at a median of 6(IQR: 2-10) days after inclusion. 108 children were retrospectively classified as having tuberculosis resulting in a prevalence of 17.9% (95% confidence intervals (CI): 15.1; 21.2). 75 (69.4%) children with tuberculosis reported cough of any duration, 32 (29.6%) cough ≥2 weeks and 11 (10.2%) tuberculosis contact history. 535 children had complete data and were included in the diagnostic prediction model. The one-step diagnostic model had 15 predictors, including Ultra, clinical, radiographic, and abdominal features, an area under the receiving operating curve (AUROC) of 0.910, and derived TDA sensitivity of 86.14% (95% CI: 78.07-91.56) and specificity of 80.88% (95% CI: 76.91-84.30). The two-step model had AUROCs of 0.750 and 0.912 for screening and diagnosis, respectively, and derived combined TDA sensitivity of 79.21% (95% CI: 70.30-85.98) and a specificity of 83.64% (95% CI: 79.87-86.82). Tuberculosis prevalence was high among hospitalised children with SAM, with atypical clinical features. TDAs achieved satisfactory diagnostic accuracy and could be used to improve diagnosis in this vulnerable group. Unitaid.

Incidence of side effects of antituberculosis drugs and their related factors in northern Iran: a retrospective cohort study.

Antituberculosis drugs may cause mild, moderate or severe adverse drug reactions (ADR) leading to poor compliance. Description of the pattern of ADR and their related factors can help tuberculosis (TB) control program as part of the WHO programs. This study aims to investigate the incidence of ADR and associated factors among TB patients in northern Iran. This is a retrospective cohort study. The required information, including year of diagnosis, age, gender, residence area, nationality, HIV co-morbidity, history of anti TB treatment and ADR, was obtained from the Deputy of Health, Mazandaran University of Medical Sciences, Iran. All data were analyzed using SPSS version 21 software. Out of 3903 TB patients, 136 (3.5%) experienced major ADR. The incidence of ADR for men and women as well as for those with and without previous treatment history were 3.9% vs. 3.3% and 5.3% vs. 3.4%, respectively (p>0.05). Multiple logistic regression models showed a higher chance of ADR among those aged over 59 compared with those aged under 29 (OR=2.63, 95% confidence interval: 1.54-4.49). Age over 59 can be considered a risk factor for ADR with anti-TB drug administration.

Reasons for loss to follow-up (LTFU) of pulmonary TB (PTB) patients: A qualitative study among Saharia, a particularly vulnerable tribal group of Madhya Pradesh, India.

Loss to follow-up (LTFU) among pulmonary tuberculosis (PTB) patients is a significant challenge for TB control. However, there is a dearth of information about the factors leading to LTFU among marginalized communities. This study highlights the factors associated with LTFU in Saharia, a tribe of Madhya Pradesh having high tuberculosis (TB) prevalence. A qualitative study was carried out during January-April 2020 among twenty-two pulmonary TB patients, recorded as LTFU in NIKSHAY, with ten treatment supporters and ten patient's family members. Semi-structured personal interview tools were used to collect the information on the history of anti-tuberculosis treatment, adverse drug events (ADE), social cognitive, behaviors, myths, and misbeliefs. The interviews were transcribed and thematically analysed to examine underlying themes. The study explored various social, behavioral factors leading to loss to follow-up among PTB patients. Drug side effects, alcoholism, social stigma, lack of awareness of the seriousness of the diseases and poor counseling are the main barriers to treatment adherence in this community. The study highlights the need to address the issues related to LTFU during TB treatment. The enhanced efforts of treatment supporters, health staff, and family & community persons must motivate and support the patients.

Decreased mortality seen in rifampicin/multidrug-resistant tuberculous meningitis treated with linezolid in Shenzhen, China

BackgroundThe morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) has shown an increasing trend globally. Its mortality rate is significantly higher than that of non-rifampicin/multidrug-resistant tuberculous meningitis (NRR/MDR-TBM). This article aimed to explore risk factors related to RR/MDR-TBM, and compare therapeutic effects of linezolid (LZD)- and non-linezolid-containing regimen for RR/MDR-TB patients in Shenzhen city. Furthermore, we aimed to find a better therapy for pathogen-negative TBM with RR/MDR-TBM related risk factors.MethodsWe conducted a retrospective study enrolling 137 hospitalized cases with confirmed TBM from June 2014 to March 2020. All patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) based on GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test results using cerebral spinal fluid (CSF). The risk factors related to RR/MDR-TBM were investigated through comparing clinical and examination features between the two groups. The mortality rate of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects. A difference of P < 0.05 was considered statistically significant.ResultsMost patients (111/137, 81%) were from southern or southwestern China, and a large proportion (72/137, 52.55%) belonged to migrant workers. 12 cases were RR/MDR-TBM (12/137, 8.8%) while 125 cases were NRR/MDR-TBM (125/137, 91.2%). The proportion of patients having prior TB treatment history in the RR/MDR-TBM group was significantly higher than that of the NRR/MDR-TBM group (6/12 vs. 12/125, 50% vs. 10.5%, P < 0.01). No significant difference was observed on other clinical and examination features between the two groups. Mortality was significantly lower in RR/MDR-TBM patients on linezolid-containing treatment regimen than those who were not (0/7 versus 3/5, 0% versus 60%, P = 0.045).ConclusionsThe main related risk factor of RR/MDR-TBM is the history of anti-tuberculosis treatment. Linezolid-containing regimen appears to lower mortality rate of RR/MDR-TBM significantly in our study. We think Linezolid should be evaluated prospectively in the treatment of RR/MDR-TBM.

A perspective of Mycobacterium Tuberculosis resistance on patients with retreat in Madagascar

Introduction: Despite advances in diagnostic and therapeutic way, drug-resistanttuberculosis is an increasingly worrying threat. Several studies suggest that one ofthe risk factors for carrying resistant Mycobacterium tuberculosis is the historyof anti-tuberculosis treatment. The objective of our study is to describe theResistance Profile of Mycobacterium Tuberculosis of patients in retreatment inMadagascar. Methods: This is a descriptive and retrospective study, carried outfrom January 2014 to September 2018 (45 months). All the cases of re-treatementrecorded in the database of the National Tuberculosis Control Program inMadagascar were included in the study.Results: We gathered 1456 cases, the average age was 40 years, there was a malepredominance(sex ratio of 2.32). In the 1302 cases where the category wasspecified, there was a predominance of relapse (76.57%). According to theculture, the incidence of rifampicin resistance was 05.36% (78/1456) including83.33% of cases of multi-resistant tuberculosis (MDR-TB) (65/78). The incidenceof isoniazid monoresistance was 05.49% (80/1456). Carrying MDR-TB is much moreimportant for patients who have failed (69.43%). The GeneXpert mtb/RIF enabledus to detect more cases of Rifampicine monoresistance (97 cases).Conclusion: cases of retreatment is a real source of the emergence of MDR-TB inMadagascar, especially cases of failure and relapse. Which is consistent with the data inthe literature. The treatment effectiveness of new cases must be maximum to preventthese cases of retreatment.Key words: drug resistance–Madagascar–profil–tuberculosis

Основні причини неефективності хіміотерапії у хворих на мультирезистентний туберкульоз легень

BACKGROUND. Research results in patients with multidrug-resistant pulmonary tuberculosis (MDR-TB) in the dynamics of treatment. OBJECTIVE. To study the main causes of chemotherapy inefficiency in patients with MDR-TB. MATERIALS AND METHODS. Comprehensive examination of 176 patients with MDR-TB, which was divided into two groups: new cases of disease (95 patients) and repeated cases (81 patients). RESULTS. The study has shown that patients with the following prognostic criteria are at high risk for the development of MDR-TB: history of anti-tuberculosis treatment, common destructive processes in the lungs, massive bacterial excretion, non-adherence to treatment. CONCLUSIONS. The main reasons for the ineffectiveness of chemotherapy in patients with MDR-TB are the process prevalence (82.8 %), massive bacterial excretion (38.2 %), the presence of multiple decay cavities (84.3 %), rapid transfer to the outpatient stage of bacterial excretion (17.9 %), termination of inpatient treatment in the intense phase (35.8 %), non-adherence to treatment (35.8 %).

Multi-center prospective survey of inflammatory bowel diseases in Kerala: More than 2000 cases.

Inflammatory bowel disease (IBD) is considered uncommon in Asia. The aim of this study was to document the demographic characteristics and clinical aspects of ulcerative colitis (UC) and Crohn's disease (CD) in Kerala, India. A survey of IBD in Kerala was performed. All gastroenterologists in the region were invited. From May 2013 to October 2015, data were collected in a standardized pro-forma. Forty-seven doctors in 34 centers contributed data. A total of 2142 patients were analyzed. This is the largest state-wide survey of IBD in India. Ulcerative colitis was diagnosed in 1112 (38 new), Crohn's disease in 980 (53 new), and 50 were unclassified (5 new). The district-wise distribution of IBD cases correlated with the District-wise Gross State Domestic Product (r= 0.69, p< 0.01). Three percent was below the age of 18. Patients with UC had more diarrhea (73% vs. 51%), bleeding PR (79% vs. 34%), and intermittent flares (35% vs. 13%) (all p< 0.01). Patients with CD had more abdominal pain (62% vs. 46%), weight loss (53% vs. 40%), fever (28% vs. 18%), and history of antituberculosis treatment (21% vs. 5%) (all p< 0.01). Compared to adults, children (below 18years) were more likely to have extensive UC (58% vs. 34%, p< 0.01) and unclassified IBD (15% vs. 2%, p< 0.01). Inflammatory bowel disease is common in Kerala, India. The disease characteristics of patients with IBD are almost similar to those from other parts of the country. Both UC and CD were seen in equal proportion in Kerala.

Analysis of extrapulmonary tuberculosis in Spain: 2007–2012 National Study

IntroductionThis study sought to study the epidemiological characteristics of the extrapulmonary tuberculosis (EPTB) in relation to pulmonary tuberculosis (PTB) from 2007 to 2012 in Spain, and plot its trend across the same period. MethodsWe conducted an analytical cross-sectional study in which the following variables were analysed: age; sex; disease site; history of antituberculosis treatment; country of birth; presence of HIV infection; and culture results. Age-related differences were ascertained using the test of comparison of proportions, and crude and adjusted ORs were calculated using linear regression models. ResultsOf the total of 44,050 cases of tuberculosis reported in the period 2007–2012 and included in the study, 31,508 (71.53%) were pulmonary tuberculosis and 12,542 (28.47%) were EPTB. EPTB rates decreased across all age groups. The main EPTB risk factor was presence of HIV infection (OR 1.39). Persons aged under 65 years had a lower risk of EPTB. ConclusionsAlthough persons aged over 65 years displayed the highest incidence, there was nevertheless a downward trend across all age groups. Whereas children showed a significant decrease in tuberculous meningitis, this was not so for all extrapulmonary forms. EPTB rates among persons born outside Spain were much higher than those among the Spanish population.

Analysis of extrapulmonary tuberculosis in Spain: 2007–2012 National Study

IntroductionThis study sought to study the epidemiological characteristics of the extrapulmonary tuberculosis (EPTB) in relation to pulmonary tuberculosis (PTB) from 2007 to 2012 in Spain, and plot its trend across the same period. MethodsWe conducted an analytical cross-sectional study in which the following variables were analysed: age; sex; disease site; history of antituberculosis treatment; country of birth; presence of HIV infection; and culture results. Age-related differences were ascertained using the test of comparison of proportions, and crude and adjusted ORs were calculated using linear regression models. ResultsOf the total of 44,050 cases of tuberculosis reported in the period 2007–2012 and included in the study, 31,508 (71.53%) were pulmonary tuberculosis and 12,542 (28.47%) were EPTB. EPTB rates decreased across all age groups. The main EPTB risk factor was presence of HIV infection (OR 1.39). Persons aged under 65 years had a lower risk of EPTB. ConclusionsAlthough persons aged over 65 years displayed the highest incidence, there was nevertheless a downward trend across all age groups. Whereas children showed a significant decrease in tuberculous meningitis, this was not so for all extrapulmonary forms. EPTB rates among persons born outside Spain were much higher than those among the Spanish population.

Prevalence and risk factors of drug-resistant tuberculosis in border provinces of Iran

Objective. Rapid detection of mycobacterium tuberculosis (MTB) resistance is a key step in the control of disease. This study aimed to identify the prevalence and accuracy of isoniazid (INH) and rifampin (RMP) resistance and their risk factors using multiplex allele-specific polymerase chain reaction (MAS-PCR) to detect such mutations. Materials and methods. In this cross-sectional study (2012–2013), 257 MTB patients from five frontier border provinces of Iran were selected and after divulging a full clinical history and undergoing a physical evaluation, the accuracy of drug resistance detection was carried out using the standard proportion test, sequencing, and GeneXpert/rifampicin (RIF) technique. Full demographic and environmental histories were evaluated. Results. The overall frequency of mutations was 34. Frequency of patients with mutations in KatG315 and at least one rpoB codon (of 516, 526, and 531 codons) were seven cases (2.7%). In comparison to the standard proportion test, the sensitivity and specificity of MAS-PCR in detecting common INH-resistant mutations were 68.75 and 100%, and in the detection of common RMP-resistant mutation were 81.8 and 100%, respectively. Also, 88.89% of KatG 315 mutations and 100% of rpoB mutations were diagnosed and compared with DNA sequencings. Compared to GeneXpert/RIF, 100% of RMP common point mutation was determined by MAS-PCR. Mutation odds were higher in males and greater in those with a history of anti-tuberculosis treatment. Conclusion. The results of this study indicated that MAS-PCR is an efficient method for rapid detection of mutations leading to RMP resistance but merely to KatG it is not satisfactory for the detection of INH resistance. Accurate and rapid detection of drug resistance is crucial in males and patients with a history of tuberculosis.

Role of pre-Xpert® screening using chest X-ray in early diagnosis of smear-negative pulmonary tuberculosis.

In a sub-district level hospital in South India, the proportion of patients with abnormal chest X-ray (CXR) was evaluated among smear-negative, Xpert® MTB/RIF (Xpert) positive individuals with pulmonary tuberculosis (PTB) symptoms; 384 smear-negative PTB individuals with PTB symptoms and without a history of anti-tuberculosis treatment underwent CXR and Xpert testing of one sputum specimen. Of 378 individuals with both Xpert and CXR results available, 14 were positive for Mycobacterium tuberculosis. Of these, 13 (92.9%) had an abnormal CXR and one was normal. This study highlights the usefulness of CXR before Xpert testing, which needs further validation.

HIV-associated sensory neuropathy in HIV-1 infected patients at the Douala General Hospital in Cameroon: a cross-sectional study

BackgroundPeripheral neuropathy (PN) which is the most common neurological complication of HIV infection is under recognised and undertreated especially in resource limited settings. This ailment which has a negative impact on the quality of life of HIV/AIDS patients exists in different clinical patterns of which HIV-associated Sensory neuropathy (HIV-SN) is the most common affecting up to two thirds of patients with advanced disease in some settings. In Cameroon where HIV is a major public health problem, the burden of HIV-SN has not yet been well defined.MethodsUsing the Brief Peripheral Neuropathy Screening (BPNS) tool validated by the AIDS Clinical Trial Group (ACTG) we carried out a cross sectional study to determine the prevalence of HIV-SN and its associated factors among HIV-1 patients at the Douala General Hospital between 1st July and 31st October 2011. HIV-SN was defined as the presence of neuropathic symptoms and at least an abnormal perception of vibrations of a 128Hz tuning fork on the great toe or abnormal ankle reflexes or both and expressed as a percentage of the study population.ResultsOut of 295 patients studied, 21% had HIV-SN. In HIV-SN patients the median duration of HIV infection was 79.8 months (IQR 46 – 107.5) and their median CD4 count 153cells/μL (IQR 80 – 280). Patient recall and clinical chart review showed that, 83.9% had neuropathic symptoms prior to HAART initiation and 16.1% after HAART initiation. Low CD4 count, history of alcohol intake and history of anti-tuberculosis treatment were strongly associated with HIV-SN (AOR 2.5, 2.8 and 2.9 respectively).ConclusionsHIV-SN is common among patients with advanced HIV infection in Cameroon. This simple diagnostic tool (BPNS) should therefore be routinely used to detect those with HIV-SN or at risk so as to minimise the negative impact it has on their quality of life.

Lethal Tuberculosis in a Previously Healthy Adult with IL-12 Receptor Deficiency

A 33-year-old man was admitted in hospital due to fever, generalized lymphadenopathy, and hepatosplenomegaly. He had a history of anti-tuberculosis treatment in the previous 3years. Despite normal chest radiograph, a sputum sample was smear-positive for acid-fast bacilli, and polymerase chain reaction was positive for Mycobacterium tuberculosis complex. Drug susceptibility test revealed resistance to isoniazid and rifampin. Evaluation of the patient's immune system revealed IL-12Rβ1 deficiency. The patient died of disseminated tuberculosis (TB), despite appropriate antibiotic treatment. This is the first IL-12 receptor-deficient patient presenting with disseminated TB in adulthood, without any previous relevant medical history. This diagnosis should be considered in selected adult patients with unexplained, overwhelming TB. IL-12Rβ1 deficiency is a genetic etiology of severe TB in adults and should be considered in adult patients with disseminated TB.

Potential of Mw as a prophylactic vaccine against pulmonary tuberculosis

Mycobacterium w (Mw), is a cultivable, non-pathogenic mycobacterium and has been tried extensively as an immunomodulator in leprosy. This has been found to be safe and has shown beneficial immunoprophylactic effect in population based, double blind placebo controlled trials in North India. These effects were also observed in the vaccine trials in South India. Keeping in view these beneficial effects and its earlier reported protective effect against tuberculosis in animals, its protective efficacy was evaluated in a rural population of about 28,948 people belonging to 272 villages in Ghatampur, Kanpur (India). The population was vaccinated with two doses (1st dose of 1x10(9) heat killed organisms followed 6 months later with a 2nd dose of 5x10(8) organisms) of Mw 10-13 years ago originally to investigate its effect against leprosy. The vaccine/placebo was given to healthy contacts of leprosy patients who had no evidence of suffering from tuberculosis. Incidence and prevalence of pulmonary tuberculosis in the present study was assessed in a blind manner by an active field survey and also retrospectively by history of anti tuberculosis treatment received by the patient in the intervening period (since vaccination), which was also corroborated by scrutinizing the medical records. Diagnosis was confirmed by standard clinical and bacteriological criteria. A total of 69 patients were diagnosed to be suffering from pulmonary tuberculosis during the survey which included 17 new sputum smear positive cases and 52 previously partially treated but still active pulmonary tuberculosis cases. The difference in the new sputum positive cases between the vaccinated (5/17) and placebo groups (12/17) was significant at 5% level of significance for 1 tailed test (Z>1.64). As 75% (52/69) of the cases had been diagnosed as suffering from pulmonary tuberculosis but had not taken adequate therapy all the cases diagnosed during the intervening period were recorded and re-analysis done. The differences are more significant at 1% level of significance for 1 tail test (Z>2.59) when all cases were analysed as a group. A small proportion 12.85% (total number=3036) of the contacts in the study population had BCG scars. On analysis of results on protection against tuberculosis in this group, BCG did provide protection against tuberculosis (p<0.01). In the placebo group the prevalence of tuberculosis was 1.11% which reduced to 0.70% for those who received Mw vaccine (p<0.01) which further decreased to 0.53% in those who had BCG scars and received Mw. These results thus provide evidence suggesting protective efficacy of Mw against pulmonary tuberculosis and that Mw merits investigation in future prospective immunoprophylactic trials along with other candidates for protection against pulmonary tuberculosis.

Prevalence of Resistance to Antituberculosis Drugs in Riyadh and A Review of Previous Reports

Resistance to antituberculosis drugs is an important cause of treatment failure. We evaluated the prevalence and pattern of antituberculosis drug resistance in the central region of Saudi Arabia, and reviewed previous reports from Saudi Arabia. We retrospectively examined the records of sputum smear and culture-positive pulmonary tuberculosis patients admitted consecutively from 1998 through 1999 in a main referral hospital in Riyadh, and analyzed drug sensitivity reports. We also reviewed previous reports on antituberculosis drug resistance in Saudi Arabia. Of 515 patients with pulmonary tuberculosis, 80 (15.5%) had resistance to at least one antituberculosis drug. Resistance to streptomycin was most frequent (9.7% ), followed by rifampicin (9.5%), isoniazid (4.3%), and ethambutol (0.2%). Resistance to one antituberculosis drug was found in 8.9%, resistance to two drugs in 5.2%, resistance to three drugs in 1.2%, and resistance to four drugs in 0.2%. Multidrug resistance (defined as resistance to at least isoniazid and rifampicin) was found in 1.9% of patients. A literature review including 6114 patients in Saudi Arabia showed that resistance against streptomycin was most common (8.8%), followed by rifampicin (8%), and isoniazid (7.2%). Of the 6114 patients, 6.8% patients were resistant to only one drug, 3.6% were resistant to two drugs, and 3.7% to three drugs. The high prevalence of rifampicin resistance and resistance to multiple drugs in the Riyadh region and in other parts of Saudi Arabia is a major challenge to the control of tuberculosis in this country. Efforts should be made to prevent the emergence of further antituberculosis drug resistance.

A Continuing Survey of Drug-Resistant Tuberculosis, New York City, April 1994

A 1991 survey showed high levels of drug resistance among tuberculosis patients in New York, NY. As a result, the tuberculosis control program was strengthened, including expanded use of directly observed therapy and improved infection control. We collected isolates from every patient in New York City with a positive culture for Mycobacterium tuberculosis during April 1994; results were compared with those in the April 1991 survey. From 1991 to 1994, the number of patients decreased from 466 to 332 patients. The percentage with isolates resistant to 1 or more antituberculosis drugs decreased from 33% to 24% (P < .01); with isolates resistant to at least isoniazid decreased from 26% to 18% (P < .05); and with isolates resistant to both isoniazid and rifampin decreased from 19% to 13% (P < .05). The number of patients with isolates resistant to both isoniazid and rifampin decreased by more than 50%. Among never previously treated patients, the percentage with resistance to 1 or more drugs decreased from 22% in 1991 to 13% in 1994 (P < .05). The number of patients with consistently positive culture results for more than 4 months decreased from 130 to 44. A history of antituberculosis treatment was the strongest predictor of drug resistance (odds ratio = 3.1; P < .001). Human immunodeficiency virus infection was associated with drug resistance among patients who never had been treated for tuberculosis. Drug-resistant tuberculosis declined significantly in New York City from 1991 to 1994. Measures to control and prevent tuberculosis were associated with a 29% decrease in the proportion of drug resistance and a 52% decrease in the number of patients with multidrug-resistant tuberculosis.