Search Repository
Resources
Investigating the evolutionary dynamics of second-line Mycobacterium tuberculosis drug resistance in Tanzania using hypercubic modelling and the Baum–Welch algorithm
Mycobacterium tuberculosis (MTB) continues to pose a significant threat to public health, particularly with the emergence of drug-resistant strains. Research shows that first-line anti-tuberculosis drugs are increasingly failing, and second-line drugs are also showing resistance. This study investigates the evolutionary dynamics of second-line drugs used against MTB, specifically Bedaquiline, Delamanid, Linezolid, Clofazimine, and Levofloxacin. Data were collected from the Tanzania National Institute of Medical Research (NIMR) at the Central Tuberculosis Reference Laborator Muhimbili Centre (CTRL). The data were analysed using a 5-hypercubic model, with parameters estimated using the Baum–Welch algorithm. The findings show that the most probable drug-resistant acquisition, independent of other drugs analysed, is Bedaquiline with a probability of 0.8660 and Levofloxacin with a probability of 0.134. The evolutionary pattern begins with Bedaquiline, followed by Levofloxacin, then Clofazimine, and finally either Linezolid or Delamanid, each with an equal probability of occurring. This highlights the evolutionary patterns of drug resistance, providing insights that can inform health experts and policymakers in developing evidence-based, effective interventions to combat this growing public health challenge. • Resistance of Mycobacterium tuberculosis to second-line drugs is growing. • The study examines resistance paths among Bedaquiline, Delamanid, Linezolid, Clofazimine, and Levofloxacin. • A 5-hypercubic model was used to analyse evolutionary drug resistance patterns. • The Baum-Welch algorithm estimated model parameters for public health insights. • Most likely paths: { } → B D Q → L F X → C F Z → L Z D → D L M or { } → B D Q → L F X → C F Z → D L M → L Z D
Implementation of WHO guidelines on management of advanced HIV disease and its impact among TB co-infected patients in Tanzania: a retrospective follow-up study.
BACKGROUND: The commonest causes of mortality in people living with HIV (PLHIV) are preventable and the majority can be attributed to undiagnosed tuberculosis (TB). National HIV/AIDS control programs are encouraged to implement the WHO package of interventions to improve survival among PLHIV. We assessed the implementation of the WHO TB-related package of care for Advanced HIV Disease (AHD) and its impact on treatment outcomes among HIV/TB patients in Tanzania. METHODS: A retrospective cohort study was employed among HIV/AIDS patients on antiretroviral therapy from 21 public health facilities in three regions (Dar es Salaam, Coastal, and Morogoro) of Tanzania. Patients enrolled in care between January 2013- June 2017 (before the introduction of the WHO guidelines) and July 2017-Sept 2018 (during the implementation of the guidelines) were recruited. Data abstraction was done from patient hospital files using a structured questionnaire uploaded on a tablet. RESULTS: Data from 2624 patients records were collected. Overall, 50% of patients with HIV had AHD with 7.8% of these co-infected with TB. Among AHD participants, 58.3% were female, 80.7% were from urban areas and 40.0% visited care and treatment centres as self-referrals. Implementation of the WHO AHD package of care was very low, ranging from 0% for Urine LF-LAM test done among patients with symptoms and signs of TB to 39.7% AHD concurrent with TB patients whose ART initiation was deferred for 2 weeks. Overall, the Proportion of AHD patients diagnosed with TB was 4.8%, Of which sputum Xpert as the first test for TB diagnosis was 4.4%. Five patients (0.6%) were documented to have received IPT at enrolment. Tailored counselling to ensure optimal adherence to ART for viral suppression was given to 12.1%. AHD patients co-infected with TB were retained in care more before the introduction of WHO AHD guideline (82.1%) compared to the period after the introduction of the guideline (53.9%) (p = 0.008). Clinical failure at 6 months among AHD patients was 10.6% before the guideline and 11.4% after the guideline. Immunological failure was observed in 1 patient (9.1%) before the guideline and 1 patient (7.1%) after the guideline. After the introduction of the guideline, mortality was 5.9% and no mortality was observed before the guideline. All the differences were not statistically significant. CONCLUSIONS: Implementation of the TB related WHO packages of care for AHD is very low. Except for TB diagnosis, other parameters did not improve with the introduction of the guidelines. More research is recommended to ascertain the effectiveness of guidelines as well as an understanding of the mechanisms involved.
Implementation of WHO guidelines on management of advanced HIV disease and its impact among TB co-infected patients in Tanzania: a retrospective follow-up study
Abstract Background: The commonest causes of mortality in people living with HIV (PLHIV) are preventable and the majority can be attributed to undiagnosed tuberculosis (TB). National HIV/AIDS control programs are encouraged to implement the WHO package of interventions to improve survival among PLHIV. We assessed the implementation of the WHO TB-related package of care for Advanced HIV Disease (AHD) and its impact on treatment outcomes among HIV/TB patients in Tanzania. Methods: A retrospective cohort study was employed among HIV/AIDS patients on antiretroviral therapy from 21 public health facilities in three regions (Dar es Salaam, Coastal, and Morogoro) of Tanzania. Patients enrolled in care between January 2013- June 2017 (before the introduction of the WHO guidelines) and July 2017-Sept 2018 (during the implementation of the guidelines) were recruited. Data abstraction was done from patient hospital files using a structured questionnaire uploaded on a tablet. Results: Data from 2624 patients records were collected. Overall, 50% of patients with HIV had AHD with 7.8% of these co-infected with TB. Among AHD participants, 58.3% were female, 80.7% were from urban areas and 40.0% visited care and treatment centres as self-referrals. Implementation of the WHO AHD package of care was very low, ranging from 0% for Urine LF-LAM test done among patients with symptoms and signs of TB to 39.7% AHD concurrent with TB patients whose ART initiation was deferred for 2 weeks. Overall, the Proportion of AHD patients diagnosed with TB was 4.8%, Of which sputum Xpert as the first test for TB diagnosis was 4.4%. Five patients (0.6%) were documented to have received IPT at enrolment. Tailored counselling to ensure optimal adherence to ART for viral suppression was given to 12.1%. AHD patients co-infected with TB were retained in care more before the introduction of WHO AHD guideline (82.1%) compared to the period after the introduction of the guideline (53.9%) (p = 0.008). Clinical failure at 6 months among AHD patients was 10.6% before the guideline and 11.4% after the guideline. Immunological failure was observed in 1 patient (9.1%) before the guideline and 1 patient (7.1%) after the guideline. After the introduction of the guideline, mortality was 5.9% and no mortality was observed before the guideline. All the differences were not statistically significant. Conclusions: Implementation of the TB related WHO packages of care for AHD is very low. Except for TB diagnosis, other parameters did not improve with the introduction of the guidelines. More research is recommended to ascertain the effectiveness of guidelines as well as an understanding of the mechanisms involved. Keywords: AHD; AHD guideline; HIV; TB; WHO.