Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis.

We conducted a retrospective study of 2555 DR-TB patients admitted to treatment between 2010 and 2016 in six geopolitical zones in Nigeria. We characterized the gender distribution of DR-TB cases and the association between demographics and clinical data, such as age, treatment category, number of previous TB treatment cycles, and geopolitical zone, with gender. The independent effects of being a male or female DR-TB patient were determined using bivariate and multivariate analyzes with statistical significance of p < 0.05 and a 95% confidence interval. Records from a total of 2555 DR-TB patients were examined for the study. A majority were male (66.9%), largest age-group was 30–39 years old (35.8%), most had MDR-TB (61.4%), were HIV-negative (76.6%), and previously treated for TB (77.1%). The southwest treatment zone had the highest proportion of DR-TB patients (36.9%), and most DR-TB diagnoses occurred in 2016 (36.9%). On bivariate analysis, age, HIV status, treatment zone, and clinical patient group in DR-TB were significantly associated with male gender. On multivariate analysis, males aged 20–29 years (AOR: 0.19, 95% CI: 0.33–0.59, p = 0.001) and HIV-positive males (AOR: 0.44, 95% CI: 0.33–0.59, p = 0.001) had lower likelihood of MDR-TB as males in the south–south treatment zone (AOR: 1.88, 95% CI: 1.23–2.85, p = 0.03), and being male and aged ≥60 years (AOR: 2.19, 95% CI: 1.05–4.54, p = 0.036) increased the probability of DR-TB. The older male population from south–southern Nigeria and women of childbearing age had lower incidence of DR-TB than men of the same age. Tailored interventions to reduce HIV and DR-TB prevalence in the general population, particularly among women of childbearing potential, and treatment support for young and older men are relevant strategies to reduce DR-TB in Nigeria.

https://www.mdpi.com/2414-6366/8/2/104/pdf?version=1675686282

Gender and Drug-Resistant Tuberculosis in Nigeria

<h2>Summary</h2> As we mark World TB Day 2024, we take this opportunity to reflect on the 2023 UN General Assembly High-Level Meeting (HLM) on the fight against tuberculosis—a milestone in the commitment towards a more coordinated, comprehensive approach to end tuberculosis globally. The UN HLM declaration on the fight against tuberculosis includes a specific pledge that all people with tuberculosis should receive a social benefits package to mitigate financial hardship. However, it is not known how this specific pledge will be realised and through which concrete actions. The use of the term financial hardship instead of WHO's key End TB Strategy indicator of catastrophic costs might prove challenging for robust evaluation of both the socioeconomic impact of tuberculosis and the effectiveness of socioeconomic support strategies to mitigate this impact. Moreover, in contrast to the financial pledges made for biomedical interventions, there was an absence of explicit investment in social protection. Such investments are imperative to facilitate successful expansion of social protection to meet the needs of people with tuberculosis and their households. Successful expansion of social protection is also dependent on political commitment and protected budgets from relevant stakeholders, including across government ministries. These strategies will help to ensure that the commitments on social protection made in the UN HLM declaration are turned into tangible actions with measurable effects. 

Achieving universal social protection for people with tuberculosis

This study aimed to determine the prevalence and molecular characterization of bedaquiline (BDQ) resistance among rifampicin-resistant tuberculosis (RR-TB) isolates collected from Zhejiang, China.A total of 245 RR-TB isolates were collected from 19 municipal TB hospitals in Zhejiang province, China between January and December 2021. Microplate assays were used to determine the minimum inhibitory concentrations (MIC) of BDQ. Whole-genome sequencing (WGS) was performed on isolates with MIC values for BDQ ≥ 0.25 μg/mL.Five (2.04%) BDQ-resistant strains were isolated from 245 tuberculosis patients. The resistance rate of BDQ was not correlated to the sex, age, treatment history, or occupation of patients. Four BDQ-resistant isolates and three BDQ-sensitive isolates were found to carry Rv0678 mutations, and one BDQ-resistant strain carried both Rv0678 and pepQ mutations. No mutations within the atpE and Rv1979c genes were observed.BDQ demonstrated strong in vitro antibacterial activity against RR-TB isolates, and the Rv0678 gene was identified as the primary mechanism contributing to BDQ resistance among RR-TB isolates from Zhejiang, China. Furthermore, in addition to the four currently known resistance-associated genes (atpE, Rv0678, Rv1979c, and pepQ), other mechanisms of resistance to BDQ may exist that need further study. 

Bedaquiline Resistance and Molecular Characterization of Rifampicin-Resistant Mycobacterium Tuberculosis Isolates in Zhejiang, China

Abstract Background Diabetes mellitus (DM) and drug-resistant tuberculosis (DR-TB) are serious global public health problems. This study aimed to explore the differences in drug resistance between DR-TB patients with and without DM. Risk factors for developing multidrug-resistant tuberculosis (MDR-TB) were also investigated among DR-TB patients. Methods The patient’s basic demographic, clinical characteristics, and drug susceptibility testing (DST) data were collected from the Chinese Disease Control Information System. Descriptive statistics were used to estimate the frequency and proportion of included variables. Categorical variables were compared using the Chi-square test or Fisher’s exact test. Chi-square tests for trends were used to determine changes and trends in MDR-TB and pre-extensively drug-resistantTB (pre-XDR-TB) patterns over time. Univariate and multivariate logistic regression analysis was used to explore the risk factors of MDR-TB. Results Compared with DR-TB patients with DM, DR-TB patients without DM had significantly higher rates of mono-resistant streptomycin (SM) and any resistance to kanamycin (KM), but significantly lower rates of any resistance to protionamide (PTO) and mono-resistance to levofloxacin (LFX), and pre-XDR-TB ( P &lt;0.05). The proportion of resistance to other anti-TB drugs was not statistically different between the DR-TB with and without DM. Among DR-TB patients without and with DM, the proportion of patients with MDR-TB and pre-XDR-TB patterns showed a significant downward trend from 2016 to 2021 ( P &lt;0.05). Among DR-TB patients without DM, male, previously treated DR-TB cases, and immigration were risk factors for MDR-TB ( P &lt;0.05). In DR-TB patients with DM, a negative sputum smear is a risk factor for MDR-TB ( P &lt;0.05). Conclusion There was no statistical difference in resistance patterns between DR-TB with and without DM, except in arbitrary resistance to PTO and KM, mono-resistant SM and LFX, and pre-XDR-TB. Great progress has been made in the prevention and control of MDR-TB and pre-XDR-TB. However, DR-TB patients with and without DM differ in their risk factors for developing MDR-TB. 

/pdf/the-differences-in-drug-resistance-between-drug-resistant-1jzl72la.pdf

The differences in drug resistance between drug-resistant tuberculosis patients with and without diabetes mellitus in northeast China: a retrospective study

BACKGROUND Gender differences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could affect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. METHODS We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged ≥ 18 years, had confirmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical significance was set at p < 0.05. RESULTS Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p < 0.001). Men were significantly more likely to be on tenofovir-based antiretroviral therapy (ART), high-dose isoniazid-containing DRTB regimen and to have history of cigarette or alcohol use. They were also more likely to have multi-drug resistant TB, isoniazid and streptomycin resistance and had higher creatinine, aspartate and gamma-glutamyl aminotransferase and total bilirubin levels. Conversely, women were more likely to be unemployed, unmarried, receive treatment from the national referral hospital and to have anemia, a capreomycin-containing DRTB regimen and zidovudine-based ART. Treatment success was observed among 437 (65.6%) and did not differ between the genders. However, mortality was higher among men than women (25.7% vs. 18.5%, p = 0.030) and men had a shorter mean (standard error) survival time (16.8 (0.42) vs. 19.0 (0.46) months), Log Rank test (p = 0.046). Predictors of mortality, after adjusting for gender, were cigarette smoking (aHR = 4.87, 95% CI 1.28-18.58, p = 0.020), an increase in alanine aminotransferase levels (aHR = 1.05, 95% CI 1.02-1.07, p < 0.001), and history of ART default (aHR = 3.86, 95% CI 1.31-11.37, p = 0.014) while a higher baseline CD4 count was associated with lower mortality (aHR = 0.94, 95% CI 0.89-0.99, p = 0.013 for every 10 cells/mm3 increment). CONCLUSION Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences.

/pdf/gender-differences-among-patients-with-drug-resistant-17f2zym10r.pdf

Gender differences among patients with drug resistant tuberculosis and HIV co-infection in Uganda: a countrywide retrospective cohort study.

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Gender differences among patients with drug resistant tuberculosis and HIV co-infection in Uganda: a countrywide retrospective cohort study.