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Introduction: With the increasing longevity of renal transplant patients, the long-term morbidities of these patients have also increased. Thus, a multidisciplinary team is needed to follow-up on these cases and adequately detect and manage the complications. Furthermore, pregnancy rates have increased in this set of patients. Case Report: In this report, we discuss briefly the posttransplant period of a female patient who had spontaneous conception with two live births and had complications such as recurrent tuberculosis, skin cancers, and chronic diarrhea. However, the patient is leading an active life even after 29 years posttransplant. Conclusion: Pregnancy is less reported in renal transplant patients, but it needs a multidisciplinary approach to the management. Furthermore, early detection and management of posttransplant complications are of utmost importance and needs extreme vigilance and care. [ABSTRACT FROM AUTHOR]

Background: The purpose of this meta-analysis (PROSPERO number: CRD42021243204) is to perform extensive and penetrating analyses on the risk factors associated with reactivation or reinfection. Methods: We searched PubMed and Embase using search terms. Risk factors (including gender, length of time between first onset and recurrent diagnosis, extrapulmonary tuberculosis, sputum smear, pulmonary cavity, Beijing family strains, diabetes, HIV infection, history of imprisonment, and immigration) were analyzed. The pooled risk ratio (RR) and 95% confidence interval (CI) were calculated with STATA 15.1. Heterogeneity was evaluated by I2 and P values. Results: The meta-analysis included 25 studies with a total of 1,477 recurrent patients. After subgroup analysis, sensitivity analysis, and testing for publication bias, it was concluded that time spanning less than two years (RR = 1.56, 95% CI: 1.33-1.85) was a risk factor for endogenous reactivation, whereas coinfection with HIV (RR = 0.72, 95% CI: 0.63-0.83), Beijing family genotype (RR = 0.46, 95% CI: 0.32-0.67), history of imprisonment (RR = 0.36, 95% CI: 0.16-0.81), and immigration (RR = 0.66, 95% CI: 0.53-0.82) were associated with exogenous reinfection. Conclusions: The recurrence interval is a risk factor for the endogenous reactivation of tuberculosis. Infection with Beijing family strains, coinfection with HIV, imprisonment, and immigration contribute to the risk of exogenous reinfection.

Background Microbial translocation is a known characteristic of pulmonary tuberculosis (PTB). Whether microbial translocation is also a biomarker of recurrence in PTB is not known. Methods We examined the presence of microbial translocation in a cohort of newly diagnosed, sputum smear, and culture positive individuals with drug-sensitive PTB. Participants were followed up for a year following the end of anti-tuberculosis treatment. They were classified as cases (in the event of recurrence, n = 30) and compared to age and gender matched controls (in the event of successful, recurrence free cure; n = 51). Plasma samples were used to measure the circulating microbial translocation markers. All the enrolled study participants were treatment naïve, HIV negative and with or without diabetes mellitus. Results Baseline levels of lipopolysaccharide (LPS) (P  = .0002), sCD14 (P  = .0191), and LPS-binding protein (LBP) (P  < .0001) were significantly higher in recurrence than controls and were associated with increased risk for recurrence, whereas intestinal fatty acid binding protein (I-FABP) and Endocab showed no association. Receiver operating characteristic (ROC) curve analysis demonstrated the utility of these individual microbial markers in discriminating recurrence from cure with high sensitivity, specificity, and area under the curve (AUC). Conclusions Recurrence following microbiological cure in PTB is characterized by heightened baseline microbial translocation. These markers can be used as a rapid prognostic tool for predicting recurrence in PTB. [ABSTRACT FROM AUTHOR]

One-third of the world's population has been infected with Mycobacterium tuberculosis (M. tuberculosis), a primary pathogen of the mammalian respiratory system, while about 10% of latent infections progress to active tuberculosis (TB), indicating that host and environmental factors may determine the outcomes such as infection clearance/persistence and treatment prognosis. The gut microbiota is essential for development of host immunity, defense, nutrition and metabolic homeostasis. Thus, the pattern of gut microbiota may contribute to M. tuberculosis infection and prognosis. In current study we characterized the differences in gut bacterial communities in new tuberculosis patients (NTB), recurrent tuberculosis patients (RTB), and healthy control. The abundance-based coverage estimator (ACE) showed the diversity index of the gut microbiota in the patients with recurrent tuberculosis was increased significantly compared with healthy controls (p < 0.05). At the phyla level, Actinobacteria and Proteobacteria, which contain many pathogenic species, were significantly enriched in the feces RTB patients. Conversely, phylum Bacteroidetes, containing a variety of beneficial commensal organisms, was reduced in the patients with the recurrent tuberculosis compared to healthy controls. The Gram-negative genus Prevotella of oral origin from phylum of Bacteroidetes and genus Lachnospira from phylum of Firmicutes were significantly decreased in both the new and recurrent TB patient groups, compared with the healthy control group (p < 0.05). We also found that there was a positive correlation between the gut microbiota and peripheral CD4+ T cell counts in the patients. This study, for the first time, showed associations between gut microbiota with tuberculosis and its clinical outcomes. Maintaining eubiosis, namely homeostasis of gut microbiota, may be beneficial for host recovery and prevention of recurrence of M. tuberculosis infection.

The purpose of this meta-analysis (PROSPERO number: CRD42021243204) is to perform extensive and penetrating analyses on the risk factors associated with reactivation or reinfection. We searched PubMed and Embase using search terms. Risk factors (including gender, length of time between first onset and recurrent diagnosis, extrapulmonary tuberculosis, sputum smear, pulmonary cavity, Beijing family strains, diabetes, HIV infection, history of imprisonment, and immigration) were analyzed. The pooled risk ratio (RR) and 95% confidence interval (CI) were calculated with STATA 15.1. Heterogeneity was evaluated by I2 and P value s. The meta-analysis included 25 studies with a total of 1,477 recurrent patients. After subgroup analysis, sensitivity analysis, and testing for publication bias, it was concluded that time spanning less than two years (RR = 1.56, 95% CI: 1.33-1.85) was a risk factor for endogenous reactivation, whereas coinfection with HIV (RR = 0.72, 95% CI: 0.63-0.83), Beijing family genotype (RR = 0.46, 95% CI: 0.32-0.67), history of imprisonment (RR = 0.36, 95% CI: 0.16-0.81), and immigration (RR = 0.66, 95% CI: 0.53-0.82) were associated with exogenous reinfection. The recurrence interval is a risk factor for the endogenous reactivation of tuberculosis. Infection with Beijing family strains, coinfection with HIV, imprisonment, and immigration contribute to the risk of exogenous reinfection. • Time spanning less than 2 years was a risk factor for endogenous reactivation • Co-infection with HIV was related to exogenous reinfection • Beijing genotype isolate was related to exogenous reinfection • History of imprisonment or immigration was associated with exogenous reinfection. [ABSTRACT FROM AUTHOR]

Abstract Background Recurrent tuberculosis (TB) contributes to the burden of TB. The study was designed to explore the time of diagnostic delay and risk of delay in patients with recurrent TB in China. Methods A total of 13,334 patients with new and recurrent TB registered in Yulin a city in China were included. The Kaplan-Meier survival curve was employed to estimate the median delay time. The mixed-effects survival model was used to identify the correlates associated with diagnostic delay. The outcome of interest in the model was"being diagnosed". Results We found that 6.5% of cases with TB were attributed to recurrence. The median delay time of recurrent TB cases (73 days) was more than twice as long as that of new TB (35 days). Individuals with recurrent TB had a higher risk of diagnostic delay than new TB (HR, 0.5, 95%CI, 0.5–0.6). Factors associated with diagnostic delay differed between new TB and recurrent TB cases. Immigrants (HR, 0.5, 95%CI, 0.3–0.9), cases notified by way of recommendation (HR, 0.6, 95%CI, 0.4–0.9) and diagnosed at TB dispensary (HR, 0.4, 95%CI, 0.3–0.6) were associated with a higher risk of a longer delay for recurrent TB cases. Conclusions The proportion of TB cases attributed to recurrence was high. Patients with recurrent TB had a longer delay time and a higher risk of diagnostic delay. Further interventions to improve diagnostic delay should focus on screening for TB in immigrants, improving public health services at the lowest healthcare level and update of TB diagnosis and management model.

Tuberculosis (TB) recurrence following successful treatment is a significant challenge in TB control programs. However, the rate of TB recurrence varies among studies. It depends on several factors, including the country/region where the investigation occurs, the study design, sample characteristics, and the anti-TB regimen used. In Yemen, a few previous studies examined the rate of TB recurrence and reported high recurrence rates, with a 5-year recurrence rate of approximately 9.5%. However, they were conducted before 2010 using the previous anti-TB regimen which was phased out and replaced with the World Health Organization’s (WHO) standard 6-month TB regimen. Consequently, this study aimed to examine the rate of TB recurrence after the implementation of the WHO standard 6-month regimen in Yemen. A prospective observational study was conducted with patients diagnosed with drug-susceptible pulmonary TB. The patients were recruited from five health centers with TB units in five governorates from January to December 2011. All the patients were followed up for five years after treatment completion. A total of 439 patients who completed the anti-TB regimen met the inclusion criteria and were included in the study. During the 5-year follow-up period, 8 patients (1.8%) died, and 13 patients (2.96%) were lost to follow-up, resulting in a final cohort of 418 patients. Of the cohort, 50.5% (n = 211) were male, while 49.5% (n = 207) were female patients. Of the patients, 129 patients (30.9%) were illiterate, 56 (13.4%) had cavitary pulmonary disease, and 6.2% (n = 26) had diabetes. The overall 5-year rate of TB recurrence in this study for the patients receiving the standard 6-month regimen was 2.9% (12/418). Moreover, almost half of the recurrent cases (41.7%; n = 5) were seen during the first year of the follow-up period. Some patient groups with risk factors recorded a higher recurrence rate, including patients with diabetes (15.4%), non-compliant patients (14.3%), pre-treatment lung cavitation patients (8.9%), illiterate patients (7.8%), and underweight patients (5.1%). In conclusion, the overall TB recurrence rate with the standard 6-month regimen was lower than that with the previous TB regimens. However, more efforts are needed to decrease TB recurrence rates further and achieve a durable cure for TB. In addition, healthcare professionals and TB control programs should consider potential risk factors of recurrence and address them to provide optimal care.

Abstract Background At least 13–20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB has critical public health importance because recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB). It is critical to understand variations in the prevalence and treatment outcomes of recurrent TB between different geographical settings. The objective of our study was to estimate the prevalence of recurrent TB among TB cases and compare risk of unfavorable treatment outcomes between rural and urban settings. Methods In a retrospective cohort study conducted in southern province of Zambia, we used mixed effects logistic regression to asses associations between explanatory and outcome variables. Primary outcome was all-cause mortality and exposure was setting (rural/urban). Data was abstracted from the facility TB registers. Results Overall 3566 recurrent TB cases were diagnosed among 25,533 TB patients. The prevalence of recurrent TB was 15.3% (95% CI: 14.8 15.9) in urban and 11.3% (95% CI: 10.7 12.0) in rural areas. Death occurred in 197 (5.5%), 103 (2.9%) were lost to follow-up, and 113 (3.2%) failed treatment. Rural settings had 70% higher risk of death (adjusted OR: 1.7; 95% CI: 1.2 2.7). Risk of lost to follow-up was twice higher in rural than urban (adjusted OR: 2.0 95% CI: 1.3 3.0). Compared to HIV-uninfected, HIV-infected individuals on Antiretroviral Treatment (ART) were 70% more likely to die (adjusted OR: 1.7; 95% CI: 1.2 3.1). Conclusion Recurrent TB prevalence was generally high in both urban and rural settings. The risk of mortality and lost to follow-up was higher among rural patients. We recommend a well-organized Directly Observed Therapy strategy adapted to setting where heightened TB control activities are focused on areas with poor treatment outcomes.

South Africa has the highest prevalence of HIV and tuberculosis (TB) co-infection globally. Recurrent TB, caused by relapse or reinfection, makes up the majority of TB cases in South Africa, and HIV infected individuals have a greater likelihood of developing recurrent TB. Given that TB remains a leading cause of death for HIV infected individuals, and correlates of TB recurrence protection/risk have yet to be defined, here we sought to understand the antibody associated mechanisms of recurrent TB by investigating the humoral response in a longitudinal cohort of HIV co-infected individuals previously treated for TB with and without recurrent disease during follow-up, in order to identify antibody correlates of protection between individuals who do not have recurrent TB and individuals who do. We used a high-throughput, "systems serology" approach to profile biophysical and functional characteristics of antibodies targeting antigens from Mycobacterium tuberculosis (Mtb). Differences in antibody profiles were noted between individuals with and without recurrent TB, albeit these differences were largely observed close to the time of re-diagnosis. Individuals with recurrent TB had decreased Mtb -antigen specific IgG3 titers, but not other IgG subclasses or IgA, compared to control individuals. These data point to a potential role for Mtb -specific IgG3 responses as biomarkers or direct mediators of protective immunity against Mtb recurrence. [ABSTRACT FROM AUTHOR]

South Africa has the highest prevalence of HIV and tuberculosis (TB) co-infection globally. Recurrent TB, caused by relapse or reinfection, makes up the majority of TB cases in South Africa, and HIV infected individuals have a greater likelihood of developing recurrent TB. Given that TB remains a leading cause of death for HIV infected individuals, and correlates of TB recurrence protection/risk have yet to be defined, here we sought to understand the antibody associated mechanisms of recurrent TB by investigating the humoral response in a longitudinal cohort of HIV co-infected individuals previously treated for TB with and without recurrent disease during follow-up, in order to identify antibody correlates of protection between individuals who do not have recurrent TB and individuals who do. We used a high-throughput, “systems serology” approach to profile biophysical and functional characteristics of antibodies targeting antigens from Mycobacterium tuberculosis (Mtb). Differences in antibody profiles were noted between individuals with and without recurrent TB, albeit these differences were largely observed close to the time of re-diagnosis. Individuals with recurrent TB had decreased Mtb-antigen specific IgG3 titers, but not other IgG subclasses or IgA, compared to control individuals. These data point to a potential role for Mtb-specific IgG3 responses as biomarkers or direct mediators of protective immunity against Mtb recurrence.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterised by an underlying immunodeficiency state, worsened by the use of immunosuppressive drugs in its treatment. Hence patients with SLE are at increased risk of opportunistic infections, one of which is tuberculosis. Tuberculosis (TB) is one of the most common infectious diseases globally, with Indonesia having the second highest prevalence in the world. Further research towards better management of these two disease entities is thus required. We report a patient with SLE flare and recurrent tuberculosis infection.

Background: Understanding the etiology of recurrent tuberculosis (rTB) is important for effective TB control. Prior to the advent of whole genome sequencing (WGS), attributing rTB to relapse or reinfection using genetic information was complicated by the limited resolution of conventional genotyping methods., Methods: We applied a systematic method of evaluating whole genome single nucleotide polymorphism (wgSNP) distances and results of phylogenetic analyses to characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska during 2008-2020. We contextualized our findings through descriptive analyses of surveillance data and results of a literature search for investigations that characterized rTB etiology using WGS., Results: The percentage of TB cases in AIAN persons in Alaska classified as recurrent episodes (11.8%) was three times the national percentage (3.9%). Of 38 recurrent episodes included in genetic analyses, we attributed 25 (65.8%) to reinfection based on wgSNP distances and phylogenetic analyses; this proportion was the highest among 16 published point estimates identified through the literature search. By comparison, we attributed 11 of 38 (28.9%) and 6 of 38 (15.8%) recurrent episodes to reinfection based on wgSNP distances alone and on conventional genotyping methods, respectively., Conclusions: WGS and attribution criteria involving genetic distances and patterns of relatedness can provide an effective means of elucidating rTB etiology. Our findings indicate that rTB occurs at high proportions among AIAN persons in Alaska and is frequently attributable to reinfection, reinforcing the importance of active surveillance and control measures to limit the spread of TB disease in Alaskan AIAN communities., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Abstract Background Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania. Methods Adult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000 inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine filtration, and circulating cathodic antigen tests. Differences between groups were assessed by χ 2, Fisher’s exact, and Wilcoxon rank sum tests. Logistic regression models were used to determine associations. Results Between August 2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and 208 (31.1%) at the rural site. Median patient age was 35 years (interquartile range [IQR]: 27–41.5 years), and 454 (68%) were males. Patients from the rural setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower median body mass index (17.5 kg/m2 vs. 18.5 kg/m2, P

Background: Recurrent tuberculosis (TB) contributes to the burden of TB. The study was designed to explore the time of diagnostic delay and risk of delay in patients with recurrent TB in China.Methods: A total of 13,334 patients with new and recurrent TB registered in Yulin a city in China were included. The Kaplan-Meier survival curve was employed to estimate the median delay time. The mixed-effects survival model was used to identify the correlates associated with diagnostic delay. The outcome of interest in the model was"being diagnosed".Results: We found that 6.5% of cases with TB were attributed to recurrence. The median delay time of recurrent TB cases (73 days) was more than twice as long as that of new TB (35 days). Individuals with recurrent TB had a higher risk of diagnostic delay than new TB (HR, 0.5, 95%CI, 0.5-0.6). Factors associated with diagnostic delay differed between new TB and recurrent TB cases. Immigrants (HR, 0.5, 95%CI, 0.3-0.9), cases notified by way of recommendation (HR, 0.6, 95%CI, 0.4-0.9) and diagnosed at TB dispensary (HR, 0.4, 95%CI, 0.3-0.6) were associated with a higher risk of a longer delay for recurrent TB cases.Conclusions: The proportion of TB cases attributed to recurrence was high. Patients with recurrent TB had a longer delay time and a higher risk of diagnostic delay. Further interventions to improve diagnostic delay should focus on screening for TB in immigrants, improving public health services at the lowest healthcare level and update of TB diagnosis and management model. [ABSTRACT FROM AUTHOR]

Background The substitution of moxifloxacin for ethambutol produced promising results for improved tuberculosis treatment outcomes. Methods We conducted an open-label, randomized trial to test whether a moxifloxacin-containing treatment regimen was superior to the standard regimen for the treatment of recurrent tuberculosis. The primary and secondary outcomes were the sputum culture conversion rate at the end of 8 weeks and the proportion of participants with a favorable outcome, respectively. Results We enrolled 196 participants; 69.9% were male and 70.4% were co-infected with human immunodeficiency virus (HIV). There was no significant difference between the study groups in the proportion of patients achieving culture conversion at the end of 8 weeks (83.0% [moxifloxacin] vs 78.5% [control]; P =.463); however, the median time to culture conversion was significantly shorter (6.0 weeks, interquartile range [IQR] 4.0–8.3) in the moxifloxacin group than the control group (7.9 weeks, IQR 4.0– 11.4; P =.018). A favorable end-of-treatment outcome was reported in 86 participants (87.8%) in the moxifloxacin group and 93 participants (94.9%) in the control group, for an adjusted absolute risk difference of −5.5 (95% confidence interval −13.8 to 2.8; P =.193) percentage points. There were significantly higher proportions of participants with Grade 3 or 4 adverse events (43.9% [43/98] vs 25.5% [25/98]; P =.01) and serious adverse events (27.6% [27/98] vs 12.2% [12/98]; P =.012) in the moxifloxacin group. Conclusions The replacement of ethambutol with moxifloxacin did not significantly improve either culture conversion rates at the end of 8 weeks or treatment success, and was associated with a higher incidence of adverse events. Clinical Trials Registration NCT02114684. [ABSTRACT FROM AUTHOR]

Background: At least 13-20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB has critical public health importance because recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB). It is critical to understand variations in the prevalence and treatment outcomes of recurrent TB between different geographical settings. The objective of our study was to estimate the prevalence of recurrent TB among TB cases and compare risk of unfavorable treatment outcomes between rural and urban settings.Methods: In a retrospective cohort study conducted in southern province of Zambia, we used mixed effects logistic regression to asses associations between explanatory and outcome variables. Primary outcome was all-cause mortality and exposure was setting (rural/urban). Data was abstracted from the facility TB registers.Results: Overall 3566 recurrent TB cases were diagnosed among 25,533 TB patients. The prevalence of recurrent TB was 15.3% (95% CI: 14.8 15.9) in urban and 11.3% (95% CI: 10.7 12.0) in rural areas. Death occurred in 197 (5.5%), 103 (2.9%) were lost to follow-up, and 113 (3.2%) failed treatment. Rural settings had 70% higher risk of death (adjusted OR: 1.7; 95% CI: 1.2 2.7). Risk of lost to follow-up was twice higher in rural than urban (adjusted OR: 2.0 95% CI: 1.3 3.0). Compared to HIV-uninfected, HIV-infected individuals on Antiretroviral Treatment (ART) were 70% more likely to die (adjusted OR: 1.7; 95% CI: 1.2 3.1).Conclusion: Recurrent TB prevalence was generally high in both urban and rural settings. The risk of mortality and lost to follow-up was higher among rural patients. We recommend a well-organized Directly Observed Therapy strategy adapted to setting where heightened TB control activities are focused on areas with poor treatment outcomes. [ABSTRACT FROM AUTHOR]

Most patients with tuberculosis respond well to treatment. Even in patients with good compliance to DOTS and sensitive to first-line drugs, treatment failure or relapse still occurs, the phenomenon of cryptic adherence needs careful evaluation. We present a case of frequent recurrence due to possible subtherapeutic levels of isoniazid (INH) and rifampicin. A 32-year-old male with no other comorbidities came with complaints of cough with expectoration with constitutional symptoms. He was treated for the primary complex at the age of 12 years and declared as cured. In 2006, he was diagnosed as right axillary TB lymphadenitis which was confirmed by histopathological examination and treated with Anti tubercular treatment (ATT) for 9 months. After 2 years (2008), he had developed left axillary lymphadenitis for which he was treated again with Anti tubercular treatment empirically. In 2016, he was diagnosed as smear-negative pulmonary tuberculosis (PTB) whose chest X-ray suggestive of PTB. Hence, he was treated with Anti tubercular treatment for 6 months, declared as cured. Now (2018), he was diagnosed as sputum-positive PTB with INH and rifampicin sensitive. Hence, we did a pharmacokinetics study, which revealed subtherapeutic levels of rifampicin and isoniazid. The patient responded well after increasing the dosage of drugs. Slow responders and patients with complications warrant the need of therapeutic drug monitoring (TDM). Drug concentrations which may be help resolve the problem of slow response to Anti Tuberculosis Therapy. TDM however is not routinely indicated in each case.

INTRODUCTION: High mortality among individuals receiving retreatment for tuberculosis (RT-TB) persists, although reasons for these poor outcomes remain unclear. METHODS: We retrospectively reviewed 394 RT-TB patients diagnosed between January 2010 and June 2016 in Accra, Ghana. RESULTS: Of RT-TB patients, 161 (40.9%) were treated empirically (negative/absent smear, culture or Xpert), of whom 30.4% (49/161) had only extrapulmonary TB signs or symptoms. Mortality during treatment was 19.4%; 15-day mortality was 10.8%. In multivariable proportional hazards regression, living with HIV (aHR=2.69 (95 CI: 1.51, 4.80], p=0.01) and previous loss-to-follow up (aHR=8.27 (95 CI: 1.10, 62.25), p=0.04) were associated with mortality, while drug susceptibility testing (DST, aHR=0.36 (95 CI: 0.13, 1.01), p=0.052) was protective. Isoniazid resistance was observed in 40% (23/58 tested) and rifampin resistance in 19.1% (12/63 tested). CONCLUSION: High rates of extrapulmonary TB and smear/culture negative disease highlight the barriers to achieving DST-driven RT-TB regimens and the need for improved diagnostics. Our finding of poly-drug resistance in rifampin-susceptible cases supports access to comprehensive first line DST. Additionally, interventions to reduce mortality, especially in HIV co-infected RT-TB patients, are urgently needed.

Introduction: high mortality among individuals receiving retreatment for tuberculosis (RT-TB) persists, although reasons for these poor outcomes remain unclear. Methods: we retrospectively reviewed 394 RT-TB patients diagnosed between January 2010 and June 2016 in Accra, Ghana. Results: of RT-TB patients, 161 (40.9%) were treated empirically (negative/absent smear, culture or Xpert), of whom 30.4% (49/161) had only extrapulmonary TB signs or symptoms. Mortality during treatment was 19.4%; 15-day mortality was 10.8%. In multivariable proportional hazards regression, living with HIV (aHR=2.69 [95 CI: 1.51, 4.80], p<0.01) and previous loss-to-follow up (aHR=8.27 (95 CI: 1.10, 62.25), p=0.04) were associated with mortality, while drug susceptibility testing (DST, aHR=0.36 (95 CI: 0.13, 1.01), p=0.052) was protective. Isoniazid resistance was observed in 40% (23/58 tested) and rifampin resistance in 19.1% (12/63 tested). Conclusion: high rates of extrapulmonary TB and smear/culture negative disease highlight the barriers to achieving DST-driven RT-TB regimens and the need for improved diagnostics. Our finding of poly-drug resistance in rifampin-susceptible cases supports access to comprehensive first line DST. Additionally, interventions to reduce mortality, especially in HIV co-infected RT-TB patients, are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania. Methods: Adult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000 inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine filtration, and circulating cathodic antigen tests. Differences between groups were assessed by χ2, Fisher's exact, and Wilcoxon rank sum tests. Logistic regression models were used to determine associations. Results: Between August 2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and 208 (31.1%) at the rural site. Median patient age was 35 years (interquartile range [IQR]: 27-41.5 years), and 454 (68%) were males. Patients from the rural setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower median body mass index (17.5 kg/m2 vs. 18.5 kg/m2, P < 0.001), a higher proportion of recurrent TB cases (9% vs. 1%, P < 0.001), and in HIV/TB co-infected patients a lower median CD4 cell counts (147 cells/μl vs. 249 cells/μl, P = 0.02) compared to those from urban Tanzania. There was no significant difference in frequencies of HIV infection, diabetes mellitus, and haemoglobin concentration levels between the two settings. The overall prevalence of helminth co-infections was 22.9% (95% confidence interval [CI]: 20.4-27.0%). The significantly higher prevalence of helminth infections at the urban site (25.7% vs. 17.3%, P = 0.018) was predominantly driven by Strongyloides stercoralis (17.0% vs. 4.8%, P < 0.001) and Schistosoma mansoni infection (4.1% vs. 16.4%, P < 0.001). Recurrent TB was associated with living in a rural setting (adjusted odds ratio [aOR]: 3.97, 95% CI: 1.16-13.67) and increasing age (aOR: 1.06, 95% CI: 1.02-1.10). Conclusions: Clinical characteristics and helminth co-infections pattern differ in TB patients in urban and rural Tanzania. The differences underline the need for setting-specific, tailored public health interventions to improve clinical management of TB and comorbidities. [ABSTRACT FROM AUTHOR]

One-third of the world's population has been infected with Mycobacterium tuberculosis (M. tuberculosis), a primary pathogen of the mammalian respiratory system, while about 10% of latent infections progress to active tuberculosis (TB), indicating that host and environmental factors may determine the outcomes such as infection clearance/persistence and treatment prognosis. The gut microbiota is essential for development of host immunity, defense, nutrition and metabolic homeostasis. Thus, the pattern of gut microbiota may contribute to M. tuberculosis infection and prognosis. In current study we characterized the differences in gut bacterial communities in new tuberculosis patients (NTB), recurrent tuberculosis patients (RTB), and healthy control. The abundance-based coverage estimator (ACE) showed the diversity index of the gut microbiota in the patients with recurrent tuberculosis was increased significantly compared with healthy controls (p < 0.05). At the phyla level, Actinobacteria and Proteobacteria, which contain many pathogenic species, were significantly enriched in the feces RTB patients. Conversely, phylum Bacteroidetes, containing a variety of beneficial commensal organisms, was reduced in the patients with the recurrent tuberculosis compared to healthy controls. The Gram-negative genus Prevotella of oral origin from phylum of Bacteroidetes and genus Lachnospira from phylum of Firmicutes were significantly decreased in both the new and recurrent TB patient groups, compared with the healthy control group (p < 0.05). We also found that there was a positive correlation between the gut microbiota and peripheral CD4+ T cell counts in the patients. This study, for the first time, showed associations between gut microbiota with tuberculosis and its clinical outcomes. Maintaining eubiosis, namely homeostasis of gut microbiota, may be beneficial for host recovery and prevention of recurrence of M. tuberculosis infection.

Tuberculosis (TB) recurrence following successful treatment is a significant challenge in TB control programs. However, the rate of TB recurrence varies among studies. It depends on several factors, including the country/region where the investigation occurs, the study design, sample characteristics, and the anti-TB regimen used. In Yemen, a few previous studies examined the rate of TB recurrence and reported high recurrence rates, with a 5-year recurrence rate of approximately 9.5%. However, they were conducted before 2010 using the previous anti-TB regimen which was phased out and replaced with the World Health Organization's (WHO) standard 6-month TB regimen. Consequently, this study aimed to examine the rate of TB recurrence after the implementation of the WHO standard 6-month regimen in Yemen. A prospective observational study was conducted with patients diagnosed with drug-susceptible pulmonary TB. The patients were recruited from five health centers with TB units in five governorates from January to December 2011. All the patients were followed up for five years after treatment completion. A total of 439 patients who completed the anti-TB regimen met the inclusion criteria and were included in the study. During the 5-year follow-up period, 8 patients (1.8%) died, and 13 patients (2.96%) were lost to follow-up, resulting in a final cohort of 418 patients. Of the cohort, 50.5% (n = 211) were male, while 49.5% (n = 207) were female patients. Of the patients, 129 patients (30.9%) were illiterate, 56 (13.4%) had cavitary pulmonary disease, and 6.2% (n = 26) had diabetes. The overall 5-year rate of TB recurrence in this study for the patients receiving the standard 6-month regimen was 2.9% (12/418). Moreover, almost half of the recurrent cases (41.7%; n = 5) were seen during the first year of the follow-up period. Some patient groups with risk factors recorded a higher recurrence rate, including patients with diabetes (15.4%), non-compliant patients (14.3%), pre-treatment lung cavitation patients (8.9%), illiterate patients (7.8%), and underweight patients (5.1%). In conclusion, the overall TB recurrence rate with the standard 6-month regimen was lower than that with the previous TB regimens. However, more efforts are needed to decrease TB recurrence rates further and achieve a durable cure for TB. In addition, healthcare professionals and TB control programs should consider potential risk factors of recurrence and address them to provide optimal care.

Tuberculosis is an infectious disease, seen among all the age groups and common in our country. If it is seen among older age groups, it causes slient clinical signs. For this reason, diagnosis of the disease may be late and the disease may develope high mortality and morbidity rate. In this study, a 78-years old patient with recurrent tuberculosis which developed axillary lymphadenopaty and spondylodiscitis while examining lung malignancy due to mediastinal lymphadenopaty, The diagnosis, clinical findings and treatment results of extrapulmonary tuberculosis were presented in older age groups. [ABSTRACT FROM AUTHOR]

Background In China, it is known that extended treatment is given to patients with pulmonary TB after they have successfully completed 6 months of first-line treatment. This practice is not officially reported to the National Tuberculosis Control Programme, so there are no data on its prevalence, its possible benefits in terms of preventing recurrent disease or the costs. This study aimed to provide information, from a single TB dispensary in Beijing, China, on the prevalence of extended anti-TB treatment and its relationship with recurrent TB. Methods Retrospective cohort study using the electronic national TB information system and dispensary medical records. Results Of 935 patients with pulmonary TB who completed 6–7 months of first-line drug treatment, 399 (43%) were given extended treatment. This was more common in patients with smear-positive disease, and those with lung cavities and more extensive radiographic lobar involvement at the time of diagnosis. Over 3–4 years' follow-up, recurrent disease was not significantly different in patients who received extended treatment (2.8%, 11/399) as compared to those who received the standard 6-month treatment (3.7%, 20/534). The median length of extended treatment was 89 days at a median cost of US$111 for drugs and US$32 for laboratory examinations. Conclusions This study shows that extended treatment is common in one TB dispensary in Beijing. Further studies are needed to determine the countrywide prevalence of this practice and ascertain more conclusively the apparent lack of benefit. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The geographical environment and living habits are different between Tibetan and Han populations. The present study aimed to investigate the risk factors of recurrent pulmonary tuberculosis (TB), and analyze the differences between the two populations. PATIENTS AND METHODS: A total of 480 TB patients, including 80 Tibetan and 80 Han patients with recurrent pulmonary TB, and 320 patients without recurrent pulmonary TB, were included in present study. All patients with pulmonary TB were diagnosed between 2000 and 2001 and followed until December 2012. Multi-variate logistic regression was used for the statistical analysis. RESULTS: Among all patients, the independent risk factors associated with recurrent pulmonary TB were no use of directly observed therapy, short course (DOTS) (HR 5.867, 95% CI 2.557-13.461), diabetes (HR 3.288, 95% CI 1.301-8.312), smoking (HR 2.387, 95% CI 1.328-4.291) and malnutrition (HR 1.910, 95% CI 1.110-3.285). The independent risk factors of recurrent pulmonary TB for the Tibetan patients included no use of DOTS and malnutrition, while the independent risk factors for the Han patients were diabetes and smoking. CONCLUSIONS: The risk factors of pulmonary TB recurrence were different between Tibetan and Han patients. To reduce the recurrent rate of pulmonary TB, especially for Tibetan populations, pursuing high-quality DOTS is essential. [ABSTRACT FROM AUTHOR]

There is evidence from international studies that tobacco smoking increases the risk of tuberculosis recurrence through its effects on the immunological and barrier functions of the airways. In this cross-sectional study, the association between current tobacco smoking and retreatment tuberculosis was studied in a population of 1 926 South African tuberculosis patients with high human immunodeficiency virus (HIV) co-infection rates. Retreatment tuberculosis was more common in male and among HIV-positive participants currently on antiretroviral treatment, or with unknown antiretroviral treatment status. However, we did not find an association between smoking and retreatment tuberculosis. A longitudinal study is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Microbial translocation is a known characteristic of pulmonary tuberculosis (PTB). Whether microbial translocation is also a biomarker of recurrence in PTB is not known., Methods: We examined the presence of microbial translocation in a cohort of newly diagnosed, sputum smear, and culture positive individuals with drug-sensitive PTB. Participants were followed up for a year following the end of anti-tuberculosis treatment. They were classified as cases (in the event of recurrence, n = 30) and compared to age and gender matched controls (in the event of successful, recurrence free cure; n = 51). Plasma samples were used to measure the circulating microbial translocation markers. All the enrolled study participants were treatment naïve, HIV negative and with or without diabetes mellitus., Results: Baseline levels of lipopolysaccharide (LPS) (P = .0002), sCD14 (P = .0191), and LPS-binding protein (LBP) (P < .0001) were significantly higher in recurrence than controls and were associated with increased risk for recurrence, whereas intestinal fatty acid binding protein (I-FABP) and Endocab showed no association. Receiver operating characteristic (ROC) curve analysis demonstrated the utility of these individual microbial markers in discriminating recurrence from cure with high sensitivity, specificity, and area under the curve (AUC)., Conclusions: Recurrence following microbiological cure in PTB is characterized by heightened baseline microbial translocation. These markers can be used as a rapid prognostic tool for predicting recurrence in PTB., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The emergence of drug resistant Mycobacterium tuberculosis has become a global threat to tuberculosis (TB) prevention and control efforts. This study aimed to determine the drug resistance profiles and DNA fingerprints of M. tuberculosis strains isolated from patients with relapsed or retreatment pulmonary TB in Chiang Rai province in northern Thailand. Significant differences in multidrug resistance (MDR) ( P = 0.025) and resistance to isoniazid ( P = 0.025) and rifampin ( P = 0.046) between first and second registrations of patients with retreatment TB were found. However, there were no significant differences in resistance to any drugs in patients with relapsed TB. The rate of MDR-TB strains was 12.2% among new patients at first registration, 22.5% among patients with recurrence who had previously undergone treatment at second registration and 12.5% at third registration. Two retreatment patients whose initial treatment had failed had developed MDR-TB with resistance to all TB drugs tested, including rifampin, isoniazid, streptomycin and ethambutol. IS 6110-RFLP analysis revealed that 66.7% (10/15 isolates) of MDR-TB belonged to the Beijing family. In most cases, IS 6110-RFLP patterns of isolates from the same patients were identical in relapse and retreatment groups. However, some pairs of isolates from retreatment patients after treatment failure had non-identical IS 6110-RFLP patterns. These results suggest that, after failure and default treatment, patients with retreatment tuberculosis have a significantly greater risk of MDR-TB, isoniazid and rifampin resistance than do other patients. [ABSTRACT FROM AUTHOR]

Background and objectives: The genetic determinants for developing TB or having recurrent TB are unknown. The present study investigated the relationship between susceptibility to tuberculosis and human tumour necrosis factor-α (TNF-α) and interleukin-10 genes (IL-10). Methods: A case–control study was conducted using two groups of cases—newly diagnosed TB (N-TB) and recurrent TB (R-TB)—and a control group. Results: One hundred and seventeen healthy controls, 80 newly diagnosed TB patients and 65 patients with recurrent TB were enrolled. There was no significant difference in the TNF-α−308 G/A genotype between the TB patient groups and the controls. The IL-10 −1082A alleles were markedly over-represented among the TB patient groups compared with the control subjects, however, there was no significant difference in the IL-10 genotype frequency between the N-TB and R-TB patient groups. Conclusion: The −1082A allele of the IL-10 gene may be important in determining susceptibility to TB, however, the −308 allele of the TNF-α gene does not affect differential TB susceptibility. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the factors associated with recurrent pulmonary tuberculosis using a well-defined, population-based tuberculosis registry system. Methods: A case–control study of persons with recurrent pulmonary tuberculosis cases (n=437) and systematically sampled nonrecurrent controls (n=442) matched by year of initial diagnosis in South Carolina. Data were acquired from the tuberculosis registry and medical chart reviews. Conditional logistic regression was used to model the relationship between recurrent disease and clinical and demographic characteristics in a multivariable analysis. Results: From 1970 through 2002, there were 15,464 pulmonary tuberculosis patients, of which 2.9% were recurrent disease. After adjusting for the covariates, odds ratios (OR) and 95% confidence intervals (95% CI) for suboptimal therapy was 6.4 (3.9–10.5), alcoholism 3.9 (2.5–6.1), interaction between treatment duration exceeding 24 months and poor compliance 3.8 (2.4–4.3), and age older than 65 years 1.9 (1.2–2.9). Our study noted an interaction between poor patient compliance and duration of treatment. Conclusion: Treatment regimen, duration of treatment, compliance, alcoholism, and older age are strong predictors of recurrent disease. Reinforcing the tuberculosis treatment guideline and applications of directly observed therapy have to remain integral components of tuberculosis control and elimination program. [Copyright &y& Elsevier]

Abstract Background Zimbabwe is a Southern African country with a high HIV-TB burden and is ranked 19th among the 22 Tuberculosis high burden countries worldwide. Recurrent TB is an important problem for TB control, yet there is limited information about treatment outcomes in relation to HIV status. This study was therefore conducted in Chitungwiza, a high density dormitory town outside the capital city, to determine in adults registered with recurrent TB how treatment outcomes were affected by type of recurrence and HIV status. Methods Data were abstracted from the Chitungwiza district TB register for all 225 adult TB patients who had previously been on anti-TB treatment and who were registered as recurrent TB from January to December 2009. The Chi-square and Fischer's exact tests were used to establish associations between categorical variables. Multivariate relative risks for associations between the various TB treatment outcomes and HIV status, type of recurrent TB, sex and age were calculated using Poisson regression with robust error variance. Results Of 225 registered TB patients with recurrent TB, 159 (71%) were HIV tested, 135 (85%) were HIV-positive and 20 (15%) were known to be on antiretroviral treatment (ART). More females were HIV-tested (75/90, 83%) compared with males (84/135, 62%). There were 103 (46%) with relapse TB, 32 (14%) with treatment after default, and 90 (40%) with "retreatment other" TB. There was one failure patient. HIV-testing and HIV-positivity were similar between patients with different types of TB. Overall, treatment success was 73% with transfer-outs at 14% being the most common adverse outcome. TB treatment outcomes did not differ by HIV status. However those with relapse TB had better treatment success compared to "retreatment other" TB patients, (adjusted RR 0.81; 95% CI 0.68 - 0.97, p = 0.02). Conclusions No differences in treatment outcomes by HIV status were established in patients with recurrent TB. Important lessons from this study include increasing HIV testing uptake, a better understanding of what constitutes "retreatment other" TB, improved follow-up of true outcomes in patients who transfer-out and better recording practices related to HIV care and treatment especially for ART.

Recurrent tuberculosis (TB) after successful TB treatment occurs due to endogenous reactivation (relapse) or exogenous reinfection. We revisited the conclusions of relapse in a high TB incidence setting that were drawn on the basis of IS 6110 restriction fragment length polymorphism (RFLP) analysis in a large retrospective cohort study in suburban Cape Town, South Africa. Using whole genome sequencing (WGS), we undertook pair-wise genome comparison of Mycobacterium tuberculosis strains cultured from diagnostic sputum samples collected at the index and recurrent TB episode for 25 recurrent TB cases who had been classified as relapse based on identical DNA fingerprint patterns in the earlier study. We found that paired strain genome sequences were identical or showed minimal variant differences in 22 of 25 recurrent TB cases, consistent with relapse. One showed 20 variant differences, suggestive of exogenous reinfection. Two of the 25 had mixed infections, each with the index episode strain detected as the dominant strain at recurrence in one of these patients, the minority strain harboured drug-resistance conferring mutations (rpoB , katG). In conclusion, our study highlights the additional value of WGS for investigating recurrent TB in settings with high infection pressure and closely related circulating strains, where the extent of re- and mixed infection may be underestimated. • IS 6110 RFLP-inferred relapse were consistent with small variant distances (WGS). • WGS can identify mixed- and reinfections with closely related strains. • Acquired drug resistance is not the driver of recurrence in this cohort. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder with recurrent bacterial and fungal infections like Staphylococcus aureus, Nocardia spp, Serratia marcescens, Burkholderia cepacia, Salmonella spp. and Aspergillus species. We present a 13-year-old male child who had 3 episodes of tuberculosis (TB) at 5 years, 8 years and 13 years of age, respectively, with no other intercurrent infections and who was diagnosed as CGD at the age of 13 years. This case highlights the possibility of phenotypic variations of CGD. The diagnosis of CGD should also be sought in all children with recurrent TB., (Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Co-trimoxazole use is the standard of care for preventing Pneumocystis jirovecii pneumonia in sub-Saharan Africa but implementation remains slow. Co-trimoxazole is self- administered with uncertain adherence. Knowledge of co-trimoxazole use among HIV infected persons is unknown., Objectives: To assess knowledge, attitudes and practices of co-trimoxazole use among HIV infected adults evaluated for recurrent PTB in Kampala, Uganda., Methods: A qualitative study utilizing 5 focus group discussions among 30 HIV infected PTB suspects at the national referral tuberculosis treatment centre in Kampala., Results: Males and females had similar median ages. 80% were currently on co-trimoxazole and 50% of participants were on HAART. Majority of participants defined co-trimoxazole as an analgesic. Few noted co-trimoxazole was a drug to treat cough and chest pain. However, few responses revealed that co-trimoxazole prevents opportunistic diseases among PLHIV. Most of participants believed HAART and anti-TB drugs work as co-trimoxazole thus it should not be taken together with them. This belief may lead to increased risk of opportunistic infections, morbidity and mortality., Conclusions: We revealed gaps in understanding of co-trimoxazole use among study participants. We therefore recommend that more facts about co-trimoxazle as prophylaxis against P. jirovecii, bacterial and diarrheal pathogens should be incorporated in VCT fact sheets.