Months Of Tuberculosis Therapy Research Articles

Sputum Smear Conversion as Prognostic Determinant of Timely Complete Therapy on Pulmonary Tuberculosis

Tuberculosis (TB) remains a major health problem worldwide. The bacteriological diagnosis of TB is confirmed by a sputum smear, which shows a positive result. Sputum culture conversion at two months of TB therapy has a higher possibility of completing therapy; however, this method is time-consuming and expensive. This study aimed to analyze the initial smear and smear conversion of sputum in the intensive phase therapy as a prognostic determinant of appropriate time-targeted therapy. This was a retrospective study on pulmonary TB patients collected from January 2016 to December 2017. The research subjects at the beginning of the intensive phase were divided into Acid-Fast Bacilli (AFB)-negative and AFB-positive (1+, 2+, 3+) sputum smears. The sputum smear examination was evaluated at the end of the intensive phase and the end of the six-month treatment. The pulmonary TB patients in this study were 430 patients, dominated by males with the main distribution age of 45-54 years. At the beginning of the intensive phase, the negative results of the AFB examination were 85.4% and the total positive results with 1+, 2+, or 3+ were 14.6%. At the end of the intensive phase, the sputum smear examination of all patients showed 100% conversion, and the sputum smear examination at the end of six months of treatment showed negative results. This study has revealed that sputum conversion at the end of the 2-month intensive phase can be used as a prognostic determinant of timely complete therapy on pulmonary tuberculosis.

Antituberculosis Drug-induced Liver Injury in Children: Incidence and Risk Factors During the Two-month Intensive Phase of Therapy.

As one of the most frequent and serious adverse reactions during tuberculosis (TB) treatment, antituberculosis drug-induced liver injury (ATLI) in children has been studied insufficiently compared with adults. We aimed to determine the incidence and risk factors of ATLI in children during the first 2 months of TB therapy. A total of 41 children with TB and treated with first-line anti-TB drugs were prospectively followed-up for the development of ATLI. Liver function tests were performed at baseline and after 2 weeks of therapy. Subsequent tests were conducted at 4, 6 and 8 weeks if the initial 2-week measurement was abnormal or if symptoms of hepatotoxicity were reported. ATLI was detected in 11 (27%) patients within 14 to 42 days from the start of therapy, with most of them (54%) occurred after 2 weeks. TB treatment was stopped immediately in 6 of 11 patients who developed ATLI, and no recurrent hepatotoxicity after drug reintroductions in these patients. Univariate analysis showed that ATLI was significantly associated with TB meningitis (P < 0.01), hypoalbuminemia (P < 0.05) and hepatotoxic comedications (P < 0.01). Age, sex, nutritional status, HIV status and baseline liver function abnormalities were not associated with ATLI. Multivariate analysis identified hypoalbuminemia and hepatotoxic comedications (both P < 0.1) tend to be independently associated with ATLI. Children with hypoalbuminemia and use of hepatotoxic comedications are suggested to be monitored closely for the development of ATLI.

P203 VEDOLIZUMAB IS SAFE AFTER ANTI-TNF-ASSOCIATED PULMONARY TUBERCULOSIS IN CROHN'S DISEASE: CASE REPORT

Anti-TNFα agents increase risk of infections due to systemic immunosuppression. Vedolizumab (VDZ) inhibits adhesions of gut-specific lymphocytes and thus may carry a lower risk. However, its safety in patients with prior tuberculosis (TB) infection is not known. We report a patient who developed TB while on anti-TNFα and was later safely maintained on VDZ. A 55-year-old Bosnian female with prior BCG vaccination was diagnosed with ileocolonic Crohn’s disease (CD) in 2008. It was poorly controlled despite infliximab & later adalimumab treatment. She developed Azathioprine-related pancreatitis and remained on prednisone from diagnosis until ileocecectomy in 2012. Shortly thereafter, she developed a cavitary lung lesion due to tuberculosis (TB). Anti-TNF α was discontinued. She completed 6 months of TB therapy. She remained in remission off IBD specific therapies for 18 months. However, she then developed recurrent abscesses and enteroenteric/enterocutaneous fistulas with intermittent courses of prednisone therapy. She underwent enterocutaneous fistula takedown, ileocolic anastomosis resection & diverting loop ileostomy. VDZ and oral methotrexate were started 3 months later with symptom resolution and inflammatory marker normalization. Colonoscopy/ileoscopy 12 months later confirmed mucosal and histological healing. Surveillance with low-dose CT for lung cancer (continued tobacco use) and TB screening a year later was non-revealing. She remains asymptomatic from a Crohn’s and TB perspective at 15 months. TB infection/reactivation is a known complication of anti-TNFα therapy. In post marketing analysis, in 66,390 patient-years of VDZ therapy, 5 patients developed TB, 2 of whom received anti-TNFα previously. Our patient is unique in that she developed active pulmonary TB after anti-TNFα therapy despite being BCG-vaccinated. She was actively followed for TB reactivation while on VDZ and responded to VDZ therapy without symptoms of TB or Crohns after 12 month follow up.

Interleukin-10 and Interferon Gamma as Prognostic Markers in Pulmonary Tuberculosis

Background: Mycobacterium tuberculosis (Mtb) infection is considered one of the most common causes of human mortality in the world. Many studies had done to explore the role of host defense in controlling the disease but many points are still unclear and need further researches. Many of pro-inflammatory and anti-inflammatory cytokines play a role in the generation and development of tuberculosis (TB) illness. Interferon gamma (IFN-γ) and interleukin-10 (IL-10) have contradictory and conflicting roles in correlation to Mtb infection severity and response to therapy. Objectives: The aim of our study was to estimate the relationship between IFN-γ and IL-10 levels and the different stages of TB and the possible effects of TB therapy on their levels. Methodology: Our study included 40 patients with active pulmonary TB and a control group of 40 healthy individuals. The levels of IFN-γ and IL-10 were measured in the patients at the start of therapy and after 3 and 6 months of TB therapy using enzyme-linked immune-sorbent assay (ELISA). Results: IFN-γ assessment by Quantiferon Gold in Tube test (QFT-GIT), for the pulmonary TB patients was higher than 0.35 IU/ml, so all patients were considered positive at the beginning of therapy. IL-10 was higher in TB patients than the control persons and the difference between the TB patients and the control persons was significant (p value <0.05). After 6 months of treatment, 6 cases not improved with treatment. IFN-γ was still high in those patients and didn't decline after 3 and 6 months of TB therapy as happened in the remaining 34 patients. The mean serum level of IL-10 declined in improved patients after therapy. However, in those 6 resistance patients, IL-10 still high after 6 months of treatment (p value < 0.05). Finally, IFN-γ didn't show difference in correlation with the disease severity, while IL-10 showed higher values with the advanced stage of Mtb (stage 3). Conclusion: IL-10 and IFN-γ could be used as prognostic markers for the success of TB therapy, but only IL-10 shows a correlation with the severity of TB infection.

The impact of diabetes on tuberculosis treatment outcomes: evidence based on a cumulative meta-analysis

Diabetes mellitus (DM) is a known risk factor for tuberculosis (TB). It is also associated with worse tuberculosis treatment outcomes. This study aimed to perform a systematic review and meta-analysis to quantitatively summarize evidence for the impact of diabetes on tuberculosis outcomes. We searched PubMed, Cochrane, and Web of Science from January 1980 to July 2015. The combinations of key words used were (((((“Tuberculosis”[Mesh]) OR (Tuberculosis OR pulmonary tuberculosis OR TB))) AND ((“Diabetes Mellitus”[Mesh]) OR (Diabetes Mellitus OR Diabetes OR DM))) AND (Outcome OR sequelae OR treatment OR therapy OR culture conversion OR failure OR death OR relapse OR recurrence)). We reviewed the full text of 70 papers and included 54 studies of which 16 reported culture conversion at 2 to 3 months, 24 reported the combined outcome of failure and death, 34 reported death, 8 reported relapse, and 7 reported drug-resistant recurrent tuberculosis. Patients with diabetes have an odds ratio (OR) through this cumulative meta-analysis for the combined outcome of failure and death of 1.96 (95 % CI, 1.64 to 2.33). The OR of death during tuberculosis treatment among the 34 unadjusted studies is 1.83 (95 % CI, 1.61 to 2.07). Diabetes is also associated with an increased risk of relapse (OR, 1.97; 95 % CI, 1.42 to 2.74). The OR for studies assessing sputum culture conversion after 2 to 3 months of tuberculosis therapy is 1.71 (95 % CI, 1.50 to 1.94). Diabetes increases the risk of failure and death combined, death, and relapse among patients with tuberculosis. This study highlights a need for increased attention to treatment of tuberculosis in people with diabetes, which may include testing for suspected diabetes, improving glucose control, and increasing clinical and therapeutic monitoring.

The impact of diabetes on tuberculosis treatment outcomes: A systematic review

BackgroundMultiple studies of tuberculosis treatment have indicated that patients with diabetes mellitus may experience poor outcomes.We performed a systematic review and meta-analysis to quantitatively summarize evidence for the impact of diabetes on tuberculosis outcomes.MethodsWe searched PubMed, EMBASE and the World Health Organization Regional Indexes from 1 January 1980 to 31 December 2010 and references of relevant articles for reports of observational studies that included people with diabetes treated for tuberculosis. We reviewed the full text of 742 papers and included 33 studies of which 9 reported culture conversion at two to three months, 12 reported the combined outcome of failure and death, 23 reported death, 4 reported death adjusted for age and other potential confounding factors, 5 reported relapse, and 4 reported drug resistant recurrent tuberculosis.ResultsDiabetes is associated with an increased risk of failure and death during tuberculosis treatment. Patients with diabetes have a risk ratio (RR) for the combined outcome of failure and death of 1.69 (95% CI, 1.36 to 2.12). The RR of death during tuberculosis treatment among the 23 unadjusted studies is 1.89 (95% CI, 1.52 to 2.36), and this increased to an effect estimate of 4.95 (95% CI, 2.69 to 9.10) among the 4 studies that adjusted for age and other potential confounding factors. Diabetes is also associated with an increased risk of relapse (RR, 3.89; 95% CI, 2.43 to 6.23). We did not find evidence for an increased risk of tuberculosis recurrence with drug resistant strains among people with diabetes. The studies assessing sputum culture conversion after two to three months of tuberculosis therapy were heterogeneous with relative risks that ranged from 0.79 to 3.25.ConclusionsDiabetes increases the risk of failure and death combined, death, and relapse among patients with tuberculosis. This study highlights a need for increased attention to treatment of tuberculosis in people with diabetes, which may include testing for suspected diabetes, improved glucose control, and increased clinical and therapeutic monitoring.

Patient satisfaction, feasibility and reliability of satisfaction questionnaire among patients with pulmonary tuberculosis in urban Uganda: a cross-sectional study

BackgroundA comprehensive understanding of the barriers to and facilitators of poor tuberculosis (TB) treatment outcome is still lacking; posing a major obstacle to finding effective solutions. Assessment of patient satisfaction in TB programs would contribute to the understanding of gaps in healthcare delivery and the specific needs of individual patients. However, tools for assessing patient satisfaction are lacking.ObjectiveTo establish patient satisfaction, the feasibility and reliability of a questionnaire for healthcare service satisfaction and a questionnaire for satisfaction with information received about TB medicines among adult TB patients attending public and private program clinics in Kampala, Uganda.MethodsIn a cross-sectional study, we recruited 133 patients of known HIV status and confirmed pulmonary TB receiving care at the public and private hospitals in Kampala, Uganda. Participants were enrolled based on length of TB treatment as follows: starting therapy, completed two months of therapy, and completed eight months of therapy. A translated and standardized 13-item patient healthcare service satisfaction questionnaire (PS-13) and the Satisfaction with Information about Medicines Scale (SIMS) tool were administered by trained interviewers. Factor analysis was used to systematically group the PS-13 questionnaire into three factors of technical quality of care, responsiveness to patient preference, and management of patient preference satisfaction subscales. The SIMS tool was analyzed with two subscales of information about the action and usage of medication and the potential problems with medication.ResultsOf the 133 participants, 35% (46/133) were starting, 33% (44/133) had completed two months, and 32% (43/133) had completed eight months of TB therapy. The male to female and public to private hospital ratios in the study population were 1:1. The PS-13 and the SIMS tools were highly acceptable and easily administered. Both scales and the subscales demonstrated acceptable internal consistency with Cronbach's alpha above 0.70. Patients that were enrolled at the public hospital had relatively lower PS-13 satisfaction scores (0.48 (95% confidence interval (CI), 0.42 - 0.52)), (0.86 (95% CI, 0.81 - 0.90)) for technical quality of care and responsiveness to patient preferences, respectively compared to patients that were enrolled at the private hospital. For potential problems SIMS subscale, male patients that were recruited at the public hospital had relatively lower satisfaction scores (0.58 (95% CI, 0.40 - 0.86)) compared to female patients after adjusting for other factors. Similarly, patients that had completed eight months of TB treatment had relatively higher satisfaction scores (1.23 (95% CI, 1.06 - 1.44)) for action and usage SIMS subscale, and higher satisfaction scores (1.09 (95% CI, 1.03 - 1.16)) for management of patient preference (PS-13 satisfaction subscale) compared to patients that were starting treatment, respectively.ConclusionThe study provides preliminary evidence that the PS-13 service satisfaction and the SIMS tools are reliable measures of patient satisfaction in TB programs. Satisfaction score findings suggest differences in patient satisfaction levels between public and private hospitals; between patients starting and those completing TB therapy.

Mycobacterium tuberculosisMicrobiologic and Clinical Treatment Outcomes in a Randomized Trial of Immediate versus CD4+‐Initiated Antiretroviral Therapy in HIV‐Infected Adults with a High CD4+Cell Count

In a prospective randomized, controlled trial in Uganda comparing the efficacy of antiretroviral therapy during tuberculosis therapy with the efficacy of tuberculosis therapy alone in HIV-infected patients with tuberculosis who have a CD4(+) cell count >350 cells/microL, it was found that antiretroviral therapy did not accelerate microbiologic, radiographic, or clinical responses to tuberculosis therapy: 18% of participants had sputum smears positive for Mycobacterium tuberculosis after 5 months of tuberculosis therapy, despite having had negative culture results. Trial registration. ClinicalTrials.gov identifier: NCT00078247 .

More on When to Start Antiretroviral Therapy in the Setting of Tuberculosis Treatment

Current WHO guidelines recommend initiation of antiretroviral therapy (ART) in all HIV-infected patients with active tuberculosis (TB), regardless of CD4-cell count, to delay progression of their HIV infection. In this study, investigators examined whether concurrent ART improves response to TB therapy in patients with high CD4-cell counts. They also assessed the significance of having sputum smears positive for acid-fast bacilli (AFB) after 5 months of TB therapy — a situation that, in the absence of sputum …

Timing of Antiretroviral Therapy Initiation in Tuberculosis Patients With AIDS

In HIV-infected tuberculosis patients with <200 CD4 lymphocytes/mm, highly active antiretroviral therapy (HAART) improves survival but can be complicated by immune reconstitution inflammatory syndrome (IRIS) and drug toxicity. We conducted a decision analysis in hypothetical cohorts of 1000 patients in which HAART was initiated during the first 2 months of tuberculosis therapy (early) or during months 2 through 6 of tuberculosis therapy (deferred) or was withheld until after tuberculosis therapy (no HAART). Outcomes assessed were 1-year mortality and the combined outcome of 1-year mortality, new AIDS-defining illness, severe IRIS, and severe drug toxicity. There were 33, 48, and 147 deaths and 497, 501, and 501 combined outcome events in the early HAART, deferred HAART, and no-HAART groups, respectively; most events were drug toxicity in the early and deferred groups and HIV-related mortality or AIDS-defining illness in the no-HAART group. In a 2-way sensitivity analysis of mortality, early HAART was favored, even with the highest reported rates of IRIS (70%) and severe drug toxicity (56%). Deferred HAART was favored over early HAART only if the IRIS-related mortality rate in the early group exceeded 4.6%. These results support early initiation of HAART in patients with AIDS, except when IRIS-related mortality rates are high.

Initiation of antiretroviral therapy in advanced AIDS with active tuberculosis: clinical experiences from Thailand

To study treatment outcomes of antiretroviral therapy (ART) initiated in advanced HIV-infected patients with active tuberculosis (TB). A retrospective cohort study was conducted in ART-naïve HIV-infected patients who presented with active TB, CD4<200 cells/microl, and had been initiated ART. ART, TB treatment and treatment outcomes of both HIV and TB were studied. There were 29 patients (19 males) with a median age of 37 (range 26-65) years. Site of TB were: lung (70%), lymph node (27.6%), and gastrointestinal tract (3.4%). At the time of TB diagnosis, median (range) CD4 cell count and HIV RNA were 74 (23-178) cells/microl and 229,000 (26,100-750,000) copies/ml, respectively. All patients received isoniazid, rifampin, ethambutol, and pyrazinamide in the first 2 months of TB therapy but the continuation phase was different depending on whether efavirenz (EFV) or nevirapine (NVP) was used. ART was initiated at a median of 8 weeks of TB treatment. All patients received NNRTI-based regimens (EFV 62.1%, NVP 37.9%). Percentage of patients with HIV RNA<50 copies/ml at 24 and 48 weeks of ART was 65.5 and 75.9%. Median CD4 cell count at 24, 48, and 72 weeks were 156, 186, and 227 cells/microl, respectively. Eighteen patients were cure; eight were treatment completed; two were treatment interrupted; and one died from CMV encephalitis. There was neither occurrence of new OI or relapse of TB in 26 patients who completed 72-week follow-up. Initiation of ART with NNRTI-based regimens at 4-12 weeks of TB treatment in advanced AIDS may be safe and effective, and may not be delayed. Further, prospective clinical studies for the optimal timing of ART initiation and ART regimen are needed.