Journal of Clinical Tuberculosis and Other Mycobacterial Diseases最新文献

Background

World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India.

Methods

Retrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included. Patients who completed treatment were followed up at 12 months.

Results

Of 17 patients, median age was 23 years (IQR = 21–30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up.

Conclusion

Concurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.

Background

The role played by type 2 diabetes mellitus (DM2) in the occurrence of recurrent tuberculosis is still uncertain. Military personnel are an occupational group with an increased risk for tuberculosis exposure due to their activities. Methods. We conducted a retrospective cohort to study the association between DM2 and recurrent TB in military workers who have been previously treated for tuberculosis at the Central Military Hospital in Lima, Peru, between 2016 and 2017. We evaluated the risk between DM2 and recurrent TB using Nelson-Aalen graphical analysis and Cox regression stratified by TB cured with hazard ratio (HR) calculation adjusted for confounders. Results. We evaluated 220 workers with a mean age of 23.2 ± 7.8 years (96.8 % male). DM2 and recurrent TB frequency were 11.8 % and 5.0 %, respectively. Those with DM (36.5 %) presented a greater proportion of recurrent TB than those without DM2 (10.5 %). The cumulative risk for recurrent TB increases faster among workers with DM2 (p = 0.025, LR chi-squared test). Cox regression stratified by type of cured TB did not show an association between DM2 and recurrent TB (HR: 3.67; 95 %CI: 1.00–13.46). Conclusion. The cumulative risk for recurrent TB increases faster in patients with DM than in those without DM2. DM2 is not associated with the time of apparition of recurrent TB in military workers.

Drug resistance among Mycobacterium tuberculosis (MTB) strains is a growing concern in developing countries. We conducted a comprehensive search for relevant studies in Iran on PubMed, Scopus, and Embase until June 12, 2020. Our study focused on determining the prevalence of antibiotic resistance in MTB isolates, with subgroup analyses based on year, location, and drug susceptibility testing (DST) methods. Statistical analyses were performed using STATA software. Our meta-analysis included a total of 47 articles. Among new TB cases, we found the following prevalence rates: Any-resistance to first-line drugs: 31 % (95 % CI, 24–38), mono-drug resistance: 15 % (95 % CI, 10–22), and multidrug resistance to first-line drugs: 6 % (95 % CI, 4–8). There was a significant variation in the rate of MDR among new TB cases based on the year of publication, location, and DST methods (P < 0.0001). We observed substantial variability in multidrug-resistant TB rates among new cases across the studies. Stratified analyses revealed that publication years and DST methods significantly affected resistance rates. Studies from southern and central Iran reported higher any-drug resistance rates, suggesting regional differences. Among retreatment cases, the prevalence rates were as follows: Any resistance: 68 % (95 % CI 58–78), mono-resistance: 19 % (95 % CI 7–34), multidrug resistance: 28 % (95 % CI 15–43). Our study revealed that the prevalence of drug-resistant TB (DR-TB) among TB cases in Iran is higher than the global average. Particularly, MDR-TB among retreatment TB cases is a significant public health issue.

Introduction

Acquired rifamycin resistance (ARR) in tuberculosis (TB) has been associated with HIV infection and can necessitate complicated TB treatment regimens, particularly in people living with HIV (PLWH). This work examines clinical characteristics and treatment outcomes of PLWH who developed ARR from 2001 to 2023 in New York City (NYC) to inform best practices for treating these patients.

Methods

PLWH who developed ARR 2001–2023 were identified from the NYC TB registry.

Results

Sixteen PLWH developed ARR; 15 were diagnosed 2001–2009 and the 16th was diagnosed in 2017. Median CD4 count was 48/mm³. On initial presentation, 14 had positive sputum cultures; of these, 12 culture-converted prior to developing ARR. Ten patients completed a course of TB treatment but subsequently relapsed; in six of these cases, ARR was discovered upon relapse, triggering treatment with a non-rifamycin-containing regimen, while in the other four, ARR was discovered during a second round of rifamycin-containing treatment. Three patients were lost to follow-up during their initial course of TB treatment and later returned to care; after being restarted on a rifamycin-containing regimen, ARR was discovered. Finally, three patients culture-converted during their first course of treatment but subsequently had cultures that grew rifamycin-resistant Mycobacterium tuberculosis prior to treatment completion, leading to changes in their treatment regimens. Among the 16 patients, eight died before being cured of TB, seven successfully completed treatment, and one was lost to follow-up.

Conclusions

PLWH should be monitored closely for the development of ARR during treatment for TB, and sputum culture conversion should be interpreted cautiously in this group. Collecting a final sputum sample may be especially important for PLWH, as treatment failure and relapse were common in this population. The decrease in the number of cases of ARR among PLWH during the study period may reflect the decrease in the total number of PLWH diagnosed with TB in NYC in recent years, improved immune status of PLWH due to increased uptake of antiretroviral drugs, and improvements in the way anti-TB regimens are designed for PLWH (such as recommending daily rather than intermittent rifamycin dosing).

Objective

We conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam’s two largest cities, Hanoi and Ho Chi Minh city.

Methods

All patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations. Genomic susceptibility predictions were made on the basis of the World Health Organization’s catalogue of mutations in Mycobacterium tuberculosis associated with drug resistance, version 2. Comparisons were made against phenotypic drug susceptibility test results where these were available. Multivariable logistic regression was used to assess risk factors for previous episodes of tuberculosis.

Results

233/265 sequenced isolates were of sufficient quality for analysis, 146 (63 %) from Ho Chi Minh City and 87 (37 %) from Hanoi. 198 (85 %) were lineage 2, 20 (9 %) were lineage 4, and 15 (6 %) were lineage 1. 17/211 (8 %) for whom HIV status was known were infected, and 109/214 (51 %) patients had had a previous episode of tuberculosis. The main risk factor for a previous episode was HIV infection (odds ratio 5.1 (95 % confidence interval 1.3–20.0); p = 0.021). Sensitivity for predicting first-line drug resistance from whole genome sequencing data was over 90 %, with the exception of pyrazinamide (85 %). For moxifloxacin and amikacin it was 50 % or less. Among rifampicin-resistant isolates, prevalence of resistance to each non-first-line drug was < 20 %.

Conclusions

Drug resistance among most MDR-TB strains in Vietnam’s two largest cities is confined largely to first-line drugs. Living with HIV is the main risk factor among patients with MDR-TB for having had a previous episode of tuberculosis.

Background

India has been estimated to have 14 % of malnourished population and a high TB incidence burden with a 26.9 lakh cases. Malnutrition and diabetes mellitus are major risk factors for tuberculosis infection. Malnutrition in patients with both tuberculosis and diabetes (TB-DM) population worsens the disease severity, treatment outcomes and increases morbidity and mortality risk.

Objective

To assess the nutritional status in patients with TB-DM compared with patients with TB and DM alone.

Method

Records from January 2016 to November 2020 for patients admitted to Kasturba Hospital, Manipal were assessed. Data pertaining to glycemic parameters, nutritional parameters, and other relevant laboratory parameters were extracted for assessment. The study population were divided into three groups i.e. patients with TB-DM, TB and DM. The statistical association was carried out with one-way ANOVA method, considering p < 0.05 as statistically significant.

Results

A total of 291 patients were included, with 97 patients in each group; among those, male and female were 86.27 % and 13.73 % respectively. Cardiovascular co-morbidity was predominant in the DM (68.04 %) and TB-DM (26.8 %) group. The mean value of HbA1c (10.47 %) was found to be highest for the TB-DM group. Low levels of albumin were reported by 71.91 % of patients of the TB group, whereas 73.68 % patients in TB-DM group had vitamin D deficiency. Moreover, higher prevalence of low MCV and MCH in the TB-DM group suggest an increased risk of iron-deficiency anemia.

Conclusion

The findings of our study reflect the need for implementation of nutritional support in patients with TB-DM.

Background

Using data from the Zimbabwe Population-based HIV Impact Assessment survey 2015–2016, we examined the TB care cascade and factors associated with not receiving TB diagnostic testing among adult PLHIV with TB symptoms.

Methods

Statistical Analysis was limited to PLHIV aged 15 years and older in HIV care. Weighted logistic regression with not receiving TB testing as outcome was adjusted for covariates with crude odd ratios (ORs) with p < 0.25. All analyses accounted for multistage survey design.

Results

Among 3507 adult PLHIV in HIV care, 2288 (59.7 %, 95 % CI:58.1–61.3) were female and 2425 (63.6 %, 95 % CI:61.1–66.1) lived in rural areas. 1197(48.7 %, 95 % CI:46.5–51.0) reported being screened for TB symptoms at their last HIV care visit. In the previous 12 months, 639 (26.0 %, 95 % CI:23.9–28.1) reported having symptoms and of those, 239 (37.8 %, 95 % CI:33.3–42.2) received TB testing. Of PLHIV tested for TB, 36 (49.5 %, 95 % CI:35.0–63.1) were diagnosed with TB; 32 (90.3 %, 95 % CI:78.9–100) of those diagnosed with TB received treatment. Never having used IPT was associated with not receiving TB testing.

Conclusion

The results suggest suboptimal utilization of TB screening and diagnostic testing among PLHIV. New approaches are needed to reach opportunities missed in the HIV/TB integrated services.

Introduction

Mycobacterium avium complex (MAC) is a complex lung infection requiring multi-disciplinary approach and management. Due to limited clinician-patient interactions, clinicians may refer patients to online resources to learn about the diagnosis, prognosis, and treatment of MAC. The American Medical Association (AMA) recommends educational materials be written at a sixth-grade reading level and the National Institutes of Health (NIH) recommends that patient education materials be written at an eighth-grade reading level; however, several evaluations found these materials inaccessible due to high literacy levels. To date, there has never been a health literacy assessment of MAC patient education materials. The study aims to assess the health literacy of online patient education materials about MAC.

Methods

The patient education materials were evaluated for readability, actionability, understandability and clarity. Readability was assessed through the Flesch-Kincaid Grade Level Scale (FkGL), SMOG Index, Coleman Liau Index (CLI), Gunning Fog Index (GFI), and Automated Readability Index (ARI). Actionability and understandability was evaluated using the Patient Education Materials Assessment Tool (PEMAT). The Centers for Disease Control (CDC) Clear Communication Index (CCI) was used to assess clarity.

Results

Ten patient education resources were evaluated: CDC, Cleveland Clinic, Mayo Clinic, JAMA, American Thoracic Society (ATS), National Jewish Health, UpToDate, CHEST, WebMD, and Medline. The mean readability scores were as follows: FkGL (9.76), SMOG index (9.82), CLI (13.54), GFI (11.66), ARI (9.15). Four patient education materials were written at a sixth-grade reading level and eight patient education materials were written at an eighth-grade reading level. The majority of the materials received a passing score for understandability but failed to achieve a passing score for actionability. Cleveland Clinic, JAMA, and ATS all received a passing clarity score, indicating that they are easy to read. No patient education materials were available on UpToDate.

Conclusion

Most patient education materials scored poorly for actionability and clarity while scoring highly for readability and understandability. This study should serve as a guide for clinicians interested in offering online education materials to their patients. Increasing access to readable MAC educational materials should be a priority for those working at the intersection of public health, clinical care, and communications.

Background

Treatment for rifampicin-resistant tuberculosis (RR-TB) has been shortened to 12 months or less, with duration depending on the regimen used and treatment response. Treatment shortening has the potential to increase the risk of relapse, with a new episode of RR-TB after cure or completion. The proportion of relapses after standardized all-oral short (12 months or less) RR-TB regimens has not yet been systematically reviewed, which is the main objective of this review.

Methods

This is a systematic review and meta-analysis. PubMed, Web of Science and Google scholar databases were systematically investigated to identify studies published between January 2018 and November 2023. Characteristics of studies, demographic data, baseline clinical condition, resistance profile, and definitions used for relapse, failure, and end-of-treatment outcomes are summarized in tables and graphs. Pooled proportions are estimated for relapse.

Results

A total of ten studies were included in this review and meta-analysis, representing 1792 participants. Seven studies were clinical trials and two were cohorts. Five studies investigated all-oral six-month regimens composed of bedaquiline, pretomanid, and linezolid (BPaL). The remaining studies assessed other standardized all-oral short regimens, with treatment duration between 6 and 12 months. Post-treatment follow-up (PTFU) duration ranged from 6 to 30 months. The pooled proportion estimate of relapse was 2·0% (95 % CI, 1·0-3·0%) for all and BPaL-based regimens. Treatment extension due to poor treatment response was poorly documented.

Conclusion

This review showed that the proportion of relapse in RR-TB patients treated with standardized short all-oral regimens was low. The low relapse proportion is similar to what was achieved for drug-susceptible Tuberculosis patients treated with first-line rifampicin-containing regimens. However, most data came from trial settings, and in some studies the post-treatment follow-up was short. Studies of large programmatic cohorts with longer post-treatment follow-up periods are needed to confirm the low relapse rate shown in the clinical trials.

A teenage girl presented with fever and altered mental status. MRI showed diffuse leptomeningeal enhancement of the brain and spine. She was diagnosed by a positive cerebrospinal fluid (CSF) culture with tuberculous (TB) meningitis and was started on anti-TB medications and corticosteroids. Her mental status improved, but she was noted to have proximal weakness of the lower extremities. In the course of tapering corticosteroids at week 11 of anti-TB therapy, she became acutely confused and febrile. MRI demonstrated interval development of tuberculomas in the brain and a mass lesion in the thoracic spine causing cord compression. Given the clinical picture was suggestive of a paradoxical reaction, the dose of corticosteroids was increased. Infliximab was added when repeat MRI revealed enlargement of the mass lesion in the spine with worsening cord compression. She was successfully tapered off of corticosteroids. Over several months, the patient’s motor function recovered fully, and she returned to ambulating without assistance.