Consequences of Disintegrated Care for Dual Tuberculosis and Diabetes in Tanzania: A Case Report on Recurrent Tuberculosis with Severe Haemoptysis in a Patient with Dysregulated Diabetes

Diabetes is known to be a risk factor for active pulmonary tuberculosis (TB) and the reactivation of latent or previous TB. It is also associated with poor TB treatment outcomes. Conversely, TB infection in itself can worsen glycaemic control temporarily and possibly lead to diabetes, among other non-communicable comorbidities. Post-TB lung disease decreases life expectancy and increases the risk of recurrent TB infection. There are efforts in low- and middle-income countries to integrate TB and diabetes healthcare services, as encouraged by the WHO and other international health organisations. However, integration measures, including bidirectional screening and coordinated care for both diseases in low- and middle-income countries, are scarce. This may lead to a lack of control over either condition. The authors present the journey of a 48-year-old man with Type 2 diabetes and previous pulmonary TB. He presented with a 2-week history of productive coughing and massive haemoptysis amounting to 500 mL in total. Recurrent pulmonary TB was confirmed by Gene Xpert, a chest X-ray, and CT of the chest. Glycaemic control improved while on TB treatment after counselling on adherence. The difficulties and dilemmas in managing and following up on a communicable and non-communicable disease traditionally cared for can be improved upon with the integration of TB/diabetes healthcare services.

Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining. No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8+ and moderate CD4+ T-cell responses, mainly to Ag85B in both vaccine groups. Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).

BackgroundUndiagnosed asymptomatic subclinical tuberculosis (TB) remains a significant threat to global TB control, accounting for a substantial proportion of cases among people living with human immunodeficiency virus (HIV)/AIDS (PLWHA). We determined incidence, progression, and outcomes of subclinical TB in antiretroviral therapy (ART)–accessing PLWHA with known previous TB in South Africa.MethodsA total of 402 adult PLWHA previously treated for TB were enrolled in the prospective Centre for the AIDS Programme of Research in South Africa TRuTH (TB Recurrence Upon TB and HIV treatment) Study. Participants were screened for TB with quarterly clinical and bacteriologic evaluation and biannual chest radiographs over 36 months. Those with suspected or confirmed TB were referred to the National TB Programme. Participants received HIV services, including ART. Incidence rate of TB was estimated using Poisson regression and descriptive statistical analyses summarized data.ResultsA total of 48 of 402 (11.9%) bacteriologically confirmed incident recurrent TB cases were identified, comprising 17 of 48 (35.4%) subclinical TB cases and 31 of 48 (64.5%) clinical TB cases. Age, sex, and body mass index were similar among subclinical, clinical, and no TB groups. Incidence rates (95% Confidence Interval [CI]) of recurrent TB overall, in clinical and subclinical TB groups were 2.3 (1.7-3.0), 1.5 (1.1-2.2), and 0.9 (0.5-1.4) per 100 person-years, respectively. In the subclinical TB group, 14 of 17 (82.4%) were diagnosed by TB culture only, 11 of 17 (64.7%) received TB treatment, and 6 of 17 (35.3%) resolved TB spontaneously.ConclusionsHigh incidence rates of recurrent subclinical TB in PLWHA highlight inadequacies of symptom-based TB screening in high TB–HIV burden settings.

OBJECTIVES/SPECIFIC AIMS: Previous research suggests that weight loss during early TB treatment (first two months of anti-TB therapy) is a predictor of poor tuberculosis (TB) treatment outcomes among HIV-negative populations, but the relationship has not been well studied in the context of HIV. We examined the association between HIV and weight change during the first two months of anti-tuberculosis treatment, and also assessed the effects of HIV and early weight change on tuberculosis (TB) treatment outcomes. METHODS/STUDY POPULATION: Adults with culture-confirmed, drug-susceptible, pulmonary TB, regardless of HIV status, were enrolled into the Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil cohort and followed on standard anti-TB therapy. For the primary analysis, we compared weight change in persons living with HIV (PLWH) and HIV-negative patients between baseline and two months using multivariable bootstrapped quantile regression and modified Poisson regression. For secondary analysis, we examined the separate effects of HIV and weight change on poor TB treatment outcome (treatment failure, TB recurrence, or death) using Cox proportional hazards regression. RESULTS/ANTICIPATED RESULTS: Among 323 participants, 45 (14%) were HIV-positive. On average, PLWH lost 0.7% (interquartile range (IQR): −5.1%, 4.4%) of their baseline body weight between baseline and two months; those without HIV gained 3.5% (IQR: 0.8%, 6.7%). After adjusting for age, sex, and baseline BMI, PLWH lost 4.1% (95% confidence interval (CI): −6.5%, −1.6%) more weight during the first two months of anti-TB treatment than HIV-negative individuals. HIV infection was associated with weight loss ≥5% (adjusted odds ratio = 9.3; 95% CI: 4.2-20.6). Regarding the secondary analysis, 14 patients had a poor TB treatment outcome: 2 treatment failures, 4 cases of recurrent TB, and 8 deaths. PLWH and patients who lost ≥5% weight had significantly increased risk of poor TB treatment outcome with hazard ratios of 8.77 (95% CI: 2.96-25.94) and 4.09 (95% CI: 1.11-15.14), respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that HIV is associated with weight loss during early TB treatment, and both HIV and early weight loss were associated with poor treatment outcome. Future research should examine the potential etiologies of these findings and identify the types of interventions that would best promote weight gain during TB treatment, especially among PLWH, in order to prevent poor TB treatment outcomes.

The purpose of this study was to evaluate the impact of human immunodeficiency virus (HIV) infection on treatment for tuberculosis (TB). The study population comprised 28,522 black Southern African gold miners. Patients with sputum culture-positive new or recurrent pulmonary TB diagnosed in 1995 were prospectively enrolled in the cohort. Directly observed therapy (DOT) was practiced and outcomes were assessed at 6 mo after treatment was begun. There were 376 cases of TB (incidence 1,318 per 100,000), of which 190 (50%) were HIV positive and 82 (22%) had recurrent TB. There was no association between HIV status and history of previous TB or drug resistance. Neither the treatment interruption rate (2%) nor the rate at which patients transferred out of the treatment program (1.6%) were associated with HIV status. Excluding deaths, cure rates were similar for HIV-positive and HIV-negative patients (89% versus 88%), but significantly lower in those with recurrent than in those with new TB (77% versus 92%). Mortality was 0.5% in HIV-negative patients versus 13.7% in HIV-positive patients, and in the latter group was associated with CD4(+) lymphocyte depletion. Autopsy examination showed that in HIV-positive patients, early mortality was due to TB whereas late deaths were most commonly due to cryptococcal pneumonia. The study showed that a well-run TB control program can result in acceptable cure rates even in a population with a very high incidence of TB and HIV infection. Particular vigilance is needed for concurrent infections, which may contribute significantly to mortality during treatment of TB in HIV-positive patients.

We evaluated the effects of previous pulmonary tuberculosis (TB) on the risk of obstructive lung disease. We analyzed population-based, the Second Korea National Health and Nutrition Examination Survey 2001. Participants underwent chest X-rays (CXR) and spirometry, and qualified radiologists interpreted the presence of TB lesion independently. A total of 3,687 underwent acceptable spirometry and CXR. Two hundreds and ninty four subjects had evidence of previous TB on CXR with no subjects having evidence of active disease. Evidence of previous TB on CXR were independently associated with airflow obstruction (adjusted odds ratios [OR] = 2.56 [95% CI 1.84-3.56]) after adjustment for sex, age and smoking history. Previous TB was still a risk factor (adjusted OR = 3.13 [95% CI 1.86-5.29]) with exclusion of ever smokers or subjects with advanced lesion on CXR. Among never-smokers, the proportion of subjects with previous TB on CXR increased as obstructive lung disease became more severe. Previous TB is an independent risk factor for obstructive lung disease, even if the lesion is minimal and TB can be an important cause of obstructive lung disease in never-smokers. Effort on prevention and control of TB is crucial in reduction of obstructive lung disease, especially in countries with more than intermediate burden of TB.

<sec id="st1"> <title>SETTING</title> The prevalence of diabetes mellitus (DM) worldwide is increasing markedly, and many countries with rising rates also have a high incidence rate of tuberculosis (TB). </sec> <sec id="st2"> <title>OBJECTIVE</title> To investigate the relationships of fasting serum glucose (FSG) and DM with TB incidence, recurrence and mortality risk in a prospective cohort study in South Korea. </sec> <sec id="st3"> <title>DESIGN</title> Our study comprised 1 267 564 Koreans who received health insurance from the National Health Insurance System, had an initial medical evaluation between 1997 and 2000 and were prospectively followed biennially. </sec> <sec id="st4"> <title>RESULTS</title> Participants with DM had a higher risk for incident TB (hazard ratio [HR] 1.81, 95%CI 1.71-1.91 in males, HR 1.33; 95%CI 1.20-1.47 in females) than those without DM. There was a strong positive trend for TB risk with rising FSG among males. The risk for recurrent TB among those with previous TB was significantly higher in males (HR 1.58, 95%CI 1.43-1.75) and in females with DM (HR 1.38, 95%CI 1.08-1.76). The increased risk of death from TB during follow-up was also significant in men (HR 1.91, 95%CI 1.87-1.95) and in women (HR 1.71, 95%CI 1.65-1.77). </sec> <sec id="st5"> <title>CONCLUSIONS</title> A diagnosis of DM is a risk factor for TB, TB recurrence and death from TB. Screening for TB should be considered among people living with DM in Korea, particularly those with severe DM. </sec>.

Despite posing a significant challenge to global tuberculosis (TB) elimination efforts, recurrent TB remains understudied due to the challenges of long-term observation. To investigate the burden of recurrent TB using data from patients with pulmonary TB (PTB) in China. This retrospective cohort study included all bacteriologically confirmed or clinically diagnosed PTB cases reported to the Tuberculosis Information Management System with completed or successful treatment outcomes from January 1, 2005, to December 31, 2021. Data were analyzed from July 15, 2022, to October 28, 2023. Newly diagnosed PTB was classified into primary, hematogenous disseminated, or secondary PTB. The primary outcome was the annual recurrence rate, stratified by disease classification, over the 17-year observation period. The recurrence rate for year n was calculated by dividing the number of patients with recurrent TB in year n by observed person-years in year n. The secondary outcome was the annual proportion of recurrent TB among reported cases and associated risk factors. Of 13 833 249 patients with TB reported to the Tuberculosis Information Management System, 10 482 271 with PTB met the inclusion criteria. Of these, 68.9% were male, 22.3% were 65 years or older, 89.6% were of Han ethnicity, and 68.4% were agricultural workers. A total of 413 936 patients experienced a recurrent TB episode after successful treatment, resulting in an overall recurrence rate of 0.47 (95% CI, 0.47-0.48) per 100 person-years. The recurrence rate for patients with primary PTB was 0.24 (95% CI, 0.22-0.26) per 100 person-years; for hematogenous disseminated PTB, 0.37 (95% CI, 0.36-0.38) per 100 person-years; and for secondary PTB, 0.48 (95% CI, 0.47-0.48) per 100 person-years. The cumulative proportion of recurrences within the first 2 years accounted for 48.9% of all recurrent cases. The proportion of recurrent cases among notified incident cases increased 1.9-fold from 4.7% in 2015 to 8.8% in 2021. Among other factors, ages 45 to 64 years (adjusted hazard ratio, 1.77 [95% CI, 1.65-1.89]) and having completed treatment (adjusted hazard ratio, 1.16 [95% CI, 1.14-1.18]) were identified as associated with recurrence. In this retrospective cohort study, the PTB recurrence rate was substantially higher than the incidence, and the proportion of recurrent cases increased. Almost half of the recurrence occurred within the first 2 years, suggesting that routine posttreatment follow-up may represent an important strategy for accelerating TB elimination.

Introduction: Pulmonary tuberculosis (TB) remains one of the most significant global health challenges, especially complicated by cases with incomplete treatment histories. The recurrence of TB poses diagnostic and therapeutic dilemmas that significantly impact patient outcomes. Case Presentation: We report a case of a 57-year-old female patient presenting with recurrent pulmonary TB after an incomplete treatment course. The patient's history revealed gaps in adherence to the prescribed TB regimen, leading to multiple relapses. In this study, we found that patients undergoing TB treatment may experience liver damage as a result of the TB medication, also known as DIH. Comprehensive diagnostic procedures, including chest radiography, sputum culture, and molecular testing, confirmed recurrent TB. The patient's clinical manifestations, treatment plan, and response to therapy are detailed. Conclusion: Recurrent TB is common, particularly in older adults, and is influenced more by environmental factors than occupation. Additionally, ATT poses risks of hepatotoxicity, especially in malnourished patients, underscoring the importance of managing side effects and addressing factors like malnutrition to prevent complications and improve outcomes. This case underscores the importance of complete adherence to TB treatment regimens and highlights the challenges in managing recurrent TB. It emphasizes the need for robust follow-up, patient education strategies, early diagnosis, and prompt intervention to prevent recurrence and enhance patient outcomes.

Many important risk factors are associated with tuberculosis (TB) recurrence; among them, smoking is the most common and modifiable behavioral factor. We aimed to assess the association of smoking status and cessation support during anti-TB treatment with subsequent TB recurrence. A 7-year prospective cohort study was performed on 634 TB patients in China. The participants were grouped by smoking status at baseline. Cox proportional hazards models were applied to analyze the association between baseline characteristics and TB recurrence. The cumulative incidence of TB recurrence was estimated by Kaplan-Meier curves. Multivariable analysis showed that patients who continued smoking during anti-TB treatment were at higher risk for TB recurrence (hazard ratio = 3.45; 95% confidence interval: 1.54-7.73) than nonsmokers. Moreover, this risk remained significant even in those who stopped smoking during anti-TB treatment (hazard ratio = 2.75; 95% confidence interval: 1.47-5.14) than nonsmokers. The association between smoking and TB recurrence was stronger for smear-positive TB patients than for smear-negative TB patients. Among all the subgroups, patients who continued smoking had a higher TB recurrence rate over the 7-year follow-up than those who successfully quit during their anti-TB treatment (log-rank statistic, p < .01). With the increase in the number of cigarettes smoked daily, the TB recurrence risk also increased accordingly (log-rank statistic, p = .02). Our findings highlight the importance of incorporating effective smoking cessation intervention measures into TB services and call for continuous monitoring of TB recurrence. Among patients who continue smoking or have a history of smoking, special attention should be given to smear-positive patients and heavy smokers when monitoring recurrence. This study provides a comprehensive picture of the association of smoking behavior and cessation efforts with TB recurrence. It shows that patients who are nonsmokers have the lowest risk of recurrence and that ex-smokers have a lower risk of recurrence than current smokers. Moreover, patients who successfully quit smoking during TB treatment have a lower risk of recurrence than those who continue smoking. Health workers should provide cessation intervention, focus on TB patients with a history of smoking, and continuously monitor TB recurrence after the completion of anti-TB treatment, particularly for smear-positive TB patients.

Relapse and recurrent tuberculosis in the context of a National Tuberculosis Control Programme

The rapid diagnosis of tuberculosis recurrence can be challenging due to persistently positive detection of Mycobacterium tuberculosis-specific DNA from sputum and bronchopulmonary samples in the absence of active disease. We compared the diagnostic accuracy of the detection of M. tuberculosis-specific DNA by either Xpert (January 2010-June 2018) or Xpert Ultra (July 2018-June 2020) and M. tuberculosis-specific ELISPOT in bronchoalveolar lavage (BAL) samples with M. tuberculosis culture results from sputum or bronchopulmonary samples in patients with suspected recurrence of pulmonary tuberculosis. Among 44 individuals with previous tuberculosis and a presumptive diagnosis of recurrent pulmonary tuberculosis, 4/44 (9.1%) were diagnosed with recurrent tuberculosis by culture. DNA of M. tuberculosis was detected by Xpert in BAL fluid in 1/4 (25%) individuals with recurrent tuberculosis and in 2/40 (5%) cases with past tuberculosis without recurrence, while BAL-ELISPOT with a cut-off of >4,000 early secretory antigenic target-6-specific or culture filtrate protein-10-specific interferon-γ-producing lymphocytes per 1 million BAL-lymphocytes was positive in 4/4 (100%) individuals with recurrent tuberculosis and in 2/40 (5%) cases of past tuberculosis without recurrence. M. tuberculosis-specific BAL-ELISPOT is more accurate than BAL-Xpert for the diagnosis of paucibacillary tuberculosis recurrence.

To study recurrence rate over a long period after recovery from previous tuberculosis history, we examined the frequency of previous tuberculosis history in patients who were admitted to our hospital in 1980-83 and in 1997-99 and the comparison was made between cases with and without culture-positive tuberculosis. The tuberculosis groups comprised of 297 patients in 1980-83 and 688 patients in 1997-99. The non-tuberculosis groups (control groups) comprised of 373 patients in 1980-83 and 1092 patients in 1997-99 with non-tuberculosis diseases other than the tuberculosis-related diseases such as non-tuberculosis mycobacteriosis, pulmonary aspergillosis, bronchiectasis, chronic bronchitis and tuberculosis sequelae. The patients with viral chronic hepatitis previously operated and transfused were also excluded as they might be operated because of pulmonary tuberculosis in the era of surgical treatment for tuberculosis. In both tuberculosis and control groups, they had previous tuberculosis history most frequently when they were twenties. In the control groups, the frequency of previous tuberculosis history among cases admitted in 1980-83 and were born in 1910-19, 20-29, 30-39, 40-49 were 15/84 (17.9%), 22/93 (23.7%), 11/77 (14.3%) and 3/43 (7.0%), respectively, and those admitted in 1997-99 were 11/70 (15.7%), 30/231 (13.0%), 28/288 (9.7%), and 10/230 (4.3%), respectively. In these 4 birth year groups, frequency of previous tuberculosis history among cases admitted in 1997-99 were significantly lower than that admitted in 1980-83 (p < 0.05, one-sided paired t-test), and the fact suggests that persons with tuberculosis history died earlier than those without it. In the tuberculosis groups, the frequencies of previous tuberculosis history among cases admitted in 1980-83 and were born in 1910-19, 20-29, 30-39 and 40-49 were 20/35 (57.1%), 31/58 (53.4%), 19/48 (39.6%), and 11/53 (20.8%), respectively, and those among cases admitted in 1997-99 were 30/99 (30.3%), 58/125 (46.4%), 22/102 (21.6%) and 17/136 (12.5%), respectively. The frequency of previous tuberculosis history among cases admitted in 1997-99 was significantly lower than that admitted in 1980-83 (p < 0.01) as was the case in the control groups. As recurrence within 5 years had occurred in only 4 out of 113 tuberculosis patients (3.5%) in the above-mentioned 4 birth year groups, almost all tuberculosis patients were assumed to have recovered completely from previous tuberculosis. Comparison between the recurrence rate from previous tuberculosis and the incidence rate from the remotely infected persons without previous tuberculosis history in the same birth year group can be done by calculating the prevalence of tuberculosis infection for each birth year group using a model of annual risk of tuberculosis infection appropriate for Japanese. The ratios between the recurrence rate from previous tuberculosis patients and the incidence rate from remotely infected persons without previous tuberculosis history were 4.71, 2.33, 1.78 and 1.11 in 1980-83 and 1.84, 3.99, 1.80 and 1.11 in 1997-99 for groups born in 1910-19, 20-29, 30-39 and 40-49, respectively. The ratio did not change systematically with time in these groups, indicating the recurrence rate did not change with time more than ten years after recovery from previous tuberculosis. The ratio was about 3 for groups born in 1910-19 and 20-29 and 1 for group born in 1940-49. Almost all patients born in 1940-49 could receive chemotherapy for tuberculosis in their twenties, while most of the patients born in 1910-29 could not. Therefore, the above-mentioned fact may reflect the recurrence rate of patients treated successfully with chemotherapy is almost the same as the incidence rate from remotely infected persons, while that the recurrence rate from previous tuberculosis patients spontaneously recovered is 3 times higher than the incidence rate from remotely infected persons.

Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3- and 4-month regimens containing moxifloxacin in a randomised clinical trial in pulmonary TB (PTB) patients in South India. New, sputum-positive, adult, HIV-negative, non-diabetic PTB patients were randomised to 3- or 4-month moxifloxacin regimens [moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E)] or to a control regimen (2H3 R3 Z3 E3 /4R3 H3 ) [C]. The 4 test regimens were 3R7 H7 Z7 E7 M7 [M3], 2R7 H7 Z7 E7 M7 /2R7 H7 M7 [M4], 2R7 H7 Z7 E7 M7 /2R3 H3 M3 [M4-I] or 2R7 H7 Z7 E7 M7 /2R3 H3 E3 M3 [M4-IE]. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24months post-treatment. The primary end point was TB recurrence post-treatment. Of 1371 patients, randomised, modified intention-to-treat (ITT) analysis was done in 1329 and per-protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. 'Favourable' response at end of treatment was 96-100% in the moxifloxacin regimensand 93% in the control regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI -3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4-I and M4-IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification. The 4-month daily moxifloxacin regimen [M4] was found to be equivalent and as safe as the 6-month thrice-weekly control regimen.

This study compared the Quality of Life (QoL) between new and recurrent pulmonary tuberculosis (TB) patients, a crucial indicator for those undergoing treatment. A cross-sectional comparative study was conducted at eight community health centres in Garut, West Java, Indonesia. Convenience sampling was used to recruit patients aged >15 years with new or recurrent pulmonary TB. QoL was assessed using the WHOQOL tool. Data were analyzed using an independent t-test. 54 new and 60 recurrent pulmonary TB patients participated. Recurrent TB patients Mean(SD) scored significantly higher in the psychological domain 58.30 (10.63) compared to new TB patients 53.70 (10.31) (p < 0.05, t-test: -2.34). New pulmonary TB patients experience greater psychological burden, highlighting the need for targeted psychological support to improve their overall QoL.