Sex differences in the impact of DM on TB recurrence [TB0099]

Diabetes mellitus (DM) was associated with a higher risk of tuberculosis (TB) recurrence, particularly in men. TB recurrence peaked two years after successful treatment, with a shorter time to recurrence in patients with DM. The association between DM and recurrent TB was significant in men but not in women, who exhibited a lower rate of recurrence. 

See also: https://tbreadingnotes.blogspot.com/2024/08/the-interaction-of-diabetes-and.html

Smoking, alcohol consumption, and chronic obstructive pulmonary disease (COPD) could act as confounding factors. It is hypothesized that impaired host immunity in DM patients, combined with smoking in men, may contribute to increased TB severity and slower microbiological responses. We could not identify a plausible explanation for the differing effects of DM on TB recurrence by sex, especially regarding DM control status. The lack of detailed information on DM severity (e.g., hemoglobin A1c levels) and treatment may have influenced our findings, as poorly controlled DM can exacerbate TB severity and recurrence.

See also: https://tbreadingnotes.blogspot.com/2024/08/the-effect-of-diabetic-control-status.html

Source: Eksombatchai, D., Jeong, D., Mok, J., Jeon, D., Kang, H.Y., Kim, H.J., Kim, H.S., Choi, H. and Kang, Y.A., 2023. Sex differences in the impact of diabetes mellitus on tuberculosis recurrence: a retrospective national cohort study. International Journal of Infectious Diseases, 127, pp.1-10.

Glycemic Control Effect on Acid-Fast Bacteria Conversion [TB0097]

Subjects with controlled RBG (Random Blood Glucose) showed a higher percentage of negative sputum smear conversion.

Subjects with controlled HbA1C also had a higher percentage of negative sputum smear conversion.

Subjects with a 31-50% decrement in RBG had the highest percentage of negative sputum smear conversion (42%).

Subjects with more than 50% RBG decrement had a lower percentage of negative sputum smear conversion (24%), compared to those with uncontrolled RBG decrement.

Source: Septa, D. and Surjadi, L.M., 2023. Glycemic Control Effect on Acid-Fast Bacteria Conversion in Diabetic Patients with Tuberculosis. Jurnal Biomedika dan Kesehatan, 6(1), pp.62-70.

Socioeconomic factors affecting TB loss to follow-up in Southeast Asia [TB0096]

TB loss to follow-up (LTFU) refers to patients who begin TB treatment but do not complete it or fail to attend follow-up appointments. According to the WHO, TB LTFU includes patients who stop treatment for more than eight consecutive weeks after undergoing at least four weeks of treatment. Several socioeconomic factors contribute to TB LTFU, such as low education levels, short-term migration, particularly across provinces, and lack of access to healthcare.

See also: https://tbreadingnotes.blogspot.com/2024/08/achieving-universal-social-protection.html

Community support, alcohol consumption, and smoking habits also increase the likelihood of LTFU. Men, individuals with lower incomes, and the unemployed are at higher risk of discontinuing TB treatment. Those whose household heads are self-employed tend to default more often compared to households led by government employees. Having health insurance and access to travel support reduces the risk of LTFU. Decentralizing treatment to facilities closer to patients' homes has also been shown to reduce treatment default rates.

See also: https://tbreadingnotes.blogspot.com/2024/08/cost-effectiveness-and-budget-impact-of.html

Alcoholics demonstrate increased odds of TB loss to follow-up (LTFU), likely due to alcohol impairing judgment, reducing adherence to treatment schedules, and diminishing the effectiveness of TB medications through drug interactions. A noticeable increase in TB LTFU rates is also observed among smokers. Smoking may contribute to this through mechanisms such as the exacerbation of pulmonary symptoms, complicating the treatment process, and potentially decreasing the efficacy of TB treatment due to the harmful effects of tobacco on the respiratory system.

Migrants face unique challenges in TB treatment, resulting in a higher risk of LTFU. These challenges include unstable housing and employment, leading to inconsistent treatment adherence. The transient nature of migrants often causes treatment interruptions due to relocation and difficulties accessing consistent health care.

Additionally, individuals with health insurance are more likely to adhere to TB treatment and follow-up protocols, highlighting the significant influence of financial barriers on patient compliance. In contrast, the financial strain of out-of-pocket payments can deter individuals from seeking or continuing TB treatment, contributing to higher loss to follow-up rates among those facing substantial out-of-pocket costs.

Source: Rani, A.Y.A., Ismail, N., Zakaria, Y. and Isa, M.R., 2024. A scoping review on socioeconomic factors affecting tuberculosis loss to follow-up in Southeast Asia. Med J Malaysia, 79(4), pp.470-476. 

Evaluating the impact of cash transfers on TB [TB0095]

In 2021, 4 million of the estimated 10 million new TB cases were not accounted for, and high rates of pre-treatment loss to follow-up hindered those identified. A major reason for this is the failure to address economic barriers faced by patients, which prevents them from completing the TB diagnostic evaluation process. 

See also: https://tbreadingnotes.blogspot.com/2024/09/tb-and-dm-increased-hospitalisations.html

TB disproportionately affects the poorest and most vulnerable populations, leading to significant losses in productivity—3 to 4 months of work for individuals, 30% of yearly household earnings for families, and 4 to 7% of GDP for countries. Accessing TB diagnostic services further threatens individuals' and households' socioeconomic status.

See also: https://tbreadingnotes.blogspot.com/2024/09/nutritional-status-in-patients-with-tb.html

Person-centred approaches that address the underlying social determinants of TB are essential. Cash transfers, whether used as incentives or as part of a broader social protection strategy, represent a promising person-centred approach to improving TB outcomes. These transfers can play a crucial role in enhancing TB treatment completion and cure rates in programmatic settings. Cash transfers helped facilitate access to TB care by covering transportation costs, and receiving such support allowed people to prioritize returning to health centers. Even a modest, one-time unconditional cash transfer can be feasibly delivered to individuals undergoing TB evaluation in high-burden, low-income settings.

See also: https://tbreadingnotes.blogspot.com/2024/09/effects-of-diabetes-mellitus-on.html

While the impact of this cash transfer on treatment initiation among those diagnosed with TB was not statistically significant, it did improve adherence to care. The intervention increased the rate of completion at each step of the TB diagnostic cascade, from referral for sputum testing to sputum submission and microbiological test results, by two to four times. This suggests that while cash transfers can effectively enable diagnostic evaluation, achieving better epidemiological outcomes, such as treatment initiation, may require more durable and comprehensive social and economic support to meet the needs of TB-affected individuals throughout the entire care cascade. There may also be differences in the effectiveness of cash transfers at different stages of TB care.

Source: Shete, P.B., Kadota, J.L., Nanyunja, G., Namale, C., Nalugwa, T., Oyuku, D., Turyahabwe, S., Kiwanuka, N., Cattamanchi, A. and Katamba, A., 2023. Evaluating the impact of cash transfers on tuberculosis (ExaCT TB): a stepped wedge cluster randomised controlled trial. ERJ open research, 9(3).

Impact of DM on immunity to LTBI [TB0092]

Latent tuberculosis infection (LTBI) is characterized by an infection with Mycobacterium tuberculosis (M.tb) without symptoms of active TB. M.tb's success lies in its ability to remain asymptomatic in a latent state, reactivating only in a minority over months, years, or even decades. The risk of reactivation varies with age at infection and any concurrent health conditions that promote TB progression. With about one-fourth of the global population estimated to have LTBI, this large pool serves as a reservoir for TB re-emergence.

See also: https://tbreadingnotes.blogspot.com/2024/07/population-health-impact-and-cost.html

Effective control of M.tb involves T cells, which aid macrophages in granuloma formation, tackling M.tb antigens. CD4+ T cells, in particular, release cytokines and chemokines with macrophage assistance, also supporting CD8+ T cell, DURT, and B cell activities. Both lymphoid and myeloid innate immune cells are crucial for the host’s defense against M.tb. However, diabetes mellitus (DM) significantly impacts the immune response, affecting cytokine levels, immune cell subsets, and increasing apoptosis and tissue fibrosis, suggesting an inflammatory role in DM pathogenesis.

See also: https://tbreadingnotes.blogspot.com/2024/07/clinical-predictors-of-pulmonary-tb.html

Individuals with LTBI and DM display reduced frequencies of myeloid and plasmacytoid dendritic cells (DC), classical and intermediate monocytes, but an elevated frequency of non-classical monocytes compared to those with LTBI alone. Reduced levels of innate lymphoid cells (ILCs), specifically ILC2 and ILC3, have been observed, while ILCs producing IFN-γ increase, and IL-13 decreases. Similarly, LTBI individuals with DM exhibit lower frequencies of γδ T cells, NK, and iNKT cells expressing various cytokines and cytotoxic markers when compared to LTBI-only individuals. Conversely, MAIT cells in LTBIDM individuals maintain or increase cytokine expression, suggesting some innate immune subsets retain TB antigen responsiveness.

See also: https://tbreadingnotes.blogspot.com/2024/07/association-between-long-term-exposure.html

DM-related alterations in innate immune markers appear linked to enhanced mycobacterial pathogenesis in LTBI individuals. Adaptive immunity, largely dependent on CD4+ T cells, particularly Th1 and Th17 cells, shows impairment in DM comorbidities. LTBI with DM individuals exhibit lower frequencies of Th1, Th2, and Th17 CD4+ T cells at baseline and following TB antigen stimulation. Neutralizing IL-10 and TGF-β partially restores these responses, highlighting the influence of these cytokines. Likewise, diminished CD8+ T cell responses to Tc1, Tc2, and Tc17 cytokines occur alongside increased cytotoxic markers (e.g., Granzyme B, perforin) in LTBI with DM cases.

See also: https://tbreadingnotes.blogspot.com/2024/07/modeling-social-environmental-and.html

Additionally, LTBI with DM individuals demonstrate lower effector memory CD4+ T cells, but elevated activated memory and atypical B cells, along with a reduction in naive B cells, signifying adaptive immune modulation in TB-DM. Collectively, DM in LTBI associates with considerable impairments in T cell activation and function, offering insights into how DM may facilitate the progression from LTBI to active TB.

IFN-γ and TNF-α are essential for protective immunity, while IL-17A, a key type 17 cytokine, plays a crucial role in memory immune responses to Mycobacterium tuberculosis (M.tb) in mice. IL-22 supports the human antimycobacterial response, and IL-1 cytokines, particularly IL-1α and IL-1β, are critical for TB resistance. Other cytokines like IL-18 and IL-12 are also vital for M.tb immunity, and IL-6 helps inhibit disease progression.

Individuals with LTBI and diabetes mellitus (DM) show decreased levels of type 1 cytokines (IFN-γ, IL-2, and TNF-α), type 17 cytokines (IL-17A, IL-17F, and IL-22), and other pro-inflammatory cytokines, such as IL-1β and IL-18, compared to those without DM. The presence of DM is associated with reduced protective cytokine production following TB antigen stimulation, potentially explaining the increased risk of active TB in individuals with LTBI and DM.

The IL-20 cytokine subfamily, which plays roles in host defense and glucose metabolism, is implicated in LTBI-DM comorbidity. LTBI-DM individuals exhibit lower plasma levels of IL-10, IL-19, IL-20, and IL-24 but increased IL-22. Additionally, they have reduced plasma adiponectin and adipsin but elevated leptin, visfatin, and PAI-1, suggesting metabolic dysfunction causes an imbalance of pro- and anti-inflammatory adipocytokines, influencing TB pathogenesis.

In newly diagnosed DM (NDM) individuals with LTBI, inflammatory markers like IL-1β, IFN-γ, and adiponectin are elevated, and IL-27 and IL-10 are higher compared to LTBI-only individuals. Meanwhile, IL-38 levels are reduced in LTBI-DM cases, indicating a unique immunological profile in LTBI-DM that may impact TB progression. DM compromises immunity, which can significantly affect the body's response to pathogens like M.tb.

Pre-diabetes (PDM), an intermediate hyperglycemic state, also impacts LTBI. LTBI-PDM individuals show reduced multifunctional Th1 and Th17 CD4+ T cell frequencies and diminished CD8+ Tc1 and Tc17 cell function upon TB antigen stimulation, correlating PDM with altered immune responses in LTBI. Lower systemic levels of IFN-γ, IL-2, TNF-α, and IL-17F suggest a pro- and anti-inflammatory cytokine imbalance in LTBI-PDM.

LTBI-PDM individuals also have reduced TB antigen-specific γδ T cells, NK, and iNKT cell responses, with lower expression of cytokines and cytotoxic markers like perforin and granzyme B. However, MAIT cells in LTBI-PDM show higher expression of type 1 and type 17 cytokines, indicating that while some innate immune cells are compromised, others remain active. These findings underscore that LTBI-PDM is marked by significant changes in immune cell activation and function, which may affect immunity to TB.

Source: Kumar, N.P., & Babu, S. (2023). Impact of diabetes mellitus on immunity to latent tuberculosis infection. Frontiers in Clinical Diabetes and Healthcare, 4, 1095467.

Temporal trends in mortality of TB attributable to HFPG in China [TB0091]

TB patients with diabetes or hyperglycemia face a higher likelihood of experiencing more severe disease and unfavorable treatment outcomes compared to those without co-morbidities. Long-term elevated blood glucose levels can impair immune cells crucial for combating TB bacteria, weakening the immune response and enabling TB bacteria to multiply and spread throughout the body, thereby increasing the risk of developing active TB. Additionally, diabetes and hyperglycemia can reduce the body's ability to effectively treat TB infections.

See also: https://tbreadingnotes.blogspot.com/2024/07/exposure-to-secondhand-smoke-and-risk.html

In China, the age-standardized mortality rates (ASMRs) for TB related to hyperglycemia were lower than the global average. Although men showed higher TB mortality rates, the reduction in mortality was smaller in men compared to women. Notably,  high fasting plasma glucose (HFPG)-related TB mortality initially increased and then decreased with age, with the most significant decrease in the average annual percentage change (AAPC) observed in the 60–64 age group. This suggests that this age range is a critical period for HFPG’s impact on TB mortality, indicating that interventions focused on managing diabetes and hyperglycemia during this life stage could significantly improve TB health outcomes.

See also: https://tbreadingnotes.blogspot.com/2024/07/the-relationship-between-malnutrition.html

In older adults, TB cases are often due to the reactivation of dormant TB lesions, which can be attributed to age-related changes in the immune system, such as a reduced ability to reactivate previously acquired immunity. Elevated TB mortality in men may also be linked to biological factors, including differences in sex hormone effects on macrophage activation. For example, oestradiol, a female sex hormone, enhances macrophage activation, whereas androgen does not have a similar effect.

See also: https://tbreadingnotes.blogspot.com/2024/07/ending-tb-in-southeast-asia.html

Mortality related to TB is associated with harmful health habits, which may be influenced by gender-specific norms and behaviors. Men often exhibit delayed healthcare-seeking behavior and poorer treatment adherence compared to women. A crucial obstacle in managing glucose levels among TB patients is adherence to medication; thus, strategies for controlling HFPG should particularly focus on men.

Source: 

Wang C, Yang X, Zhang H, Zhang Y, Tao J, Jiang X and Wu C (2023) Temporal trends in mortality of tuberculosis attributable to high fasting plasma glucose in China from 1990 to 2019: a joinpoint regression and age-period-cohort analysis. Front. Public Health 11:1225931.

 

LTBI in health-care workers in the government sector in Brunei Darussalam [TB0088]

The annual incidence rate of LTBI in health-care workers in the government sector in Brunei Darussalam ranged from 8.1 to 24.6, with an average of 14.6 over the 4-year period. When comparing treatment acceptance among subgroups, only gender showed statistical significance, with females demonstrating significantly higher treatment acceptance.

Syafiq, N.J.M., Trivedi, A.A., Lai, A., Fontelera, M.P.A. and Lim, M.A., 2023. Latent tuberculosis infection in health-care workers in the government sector in Brunei Darussalam: A cross-sectional study. Journal of Integrative Nursing, 5(3), pp.197-202.

https://journals.lww.com/jinm/fulltext/2023/05030/latent_tuberculosis_infection_in_health_care.6.aspx 

Population-based mass TB screening intervention among persons with DM

·  Technology for TB Control: While the technology to control TB exists, it is generally underused.

·  DOTS (Directly Observed Treatment, Short-course):

• Originally referred to directly observed treatment with short-course chemotherapy.
• Now a broader public health strategy with five key elements:
1. Political commitment.
2. Case detection through sputum smear microscopy, mostly among self-referring, symptomatic patients.
3. Standard short-course chemotherapy with supportive patient management, including DOT.
4. Reliable drug supply system.
5. Standardized recording and reporting system, including treatment outcome evaluations.

·  MDG Framework for TB Control:

• Comprises two DOTS-focused measures:
• Case detection.
• Treatment success.
• Includes three impact measures applicable to TB control in general:
• Incidence.
• Prevalence.
• Deaths.
• Promotes epidemiological evaluation beyond DOTS and a comprehensive TB control approach.

·  Comprehensive Approach Beyond DOTS:

• Prevention methods and improved patient care.
• Engaging public and private clinicians, especially for patients with HIV or drug-resistant TB.
• Integration of new technologies and optimization of existing tools.

·  Estimating TB Incidence Rates:

• Rarely measured directly; often estimated from:
• Population-based surveys on M. tuberculosis infection or TB disease prevalence.
• Independent, qualitative assessments of surveillance systems.
• Accuracy limitations due to challenges in calculating incidence from prevalence.

·  Regional TB Management Challenges:

• Africa and Eastern Europe face TB control challenges linked to HIV/AIDS and drug resistance.
• Region-specific solutions are needed for these unique problems.

·  DOTS Limitations and Expansion:

• By 2003, DOTS had nearly maxed out the utility of public notification systems.
• Next steps involve:
• Adapting DOTS for non-public healthcare facilities (e.g., in Indonesia).
• Encouraging all medical practitioners to adopt the basic DOTS care package.
• Expanding health services to areas lacking professional healthcare.

·  Factors Influencing TB Incidence and Death Rates:

• Not solely determined by drug treatment; other factors include:
• Nutritional status, tobacco and alcohol use.
• Other infections and genetic susceptibility.
• These determinants warrant further study to fully understand TB dynamics.

·  TB Death Statistics:

• Ideally sourced from reliable vital registration systems.
• Many poorer countries lack systematic or accurate cause-of-death records.

Dye, C., Watt, C.J., Bleed, D.M., Hosseini, S.M. and Raviglione, M.C., 2005. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. Jama, 293(22), pp.2767-2775. 

==-==

Liu, Q., You, N., Wen, J., Wang, J., Ge, Y., Shen, Y., Ding, X., Lu, P., Chen, C., Zhu, B. and Zhu, L., 2023. Yield and efficiency of a population-based mass tuberculosis screening intervention among persons with diabetes in Jiangsu Province, China. Clinical Infectious Diseases, 77(1), pp.103-111. 

Feasibility and Focus: Mass tuberculosis (TB) screening among persons with diabetes (PWD) is feasible but may not be cost-efficient due to low detection rates.

Cost Efficiency: The high costs were largely driven by diabetes management rather than TB-related expenses.

Targeted Screening: Concentrating screening efforts in populations with at least 100 TB cases per 100,000 persons is effective and should be continued.

Risk-Stratified Approaches: Risk-stratified screening could be more practical in settings with low to medium TB burden.

Symptom Screening Limitations: Relying solely on symptom screening is insufficient for TB detection, highlighting the need for more comprehensive methods.

Program Integration: Successful implementation required collaboration between diabetes and TB control programs, leveraging existing community-based diabetes screening efforts.

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Alisjahbana, B., Sahiratmadja, E., Nelwan, E.J., Purwa, A.M., Ahmad, Y., Ottenhoff, T.H., Nelwan, R.H., Parwati, I., Meer, J.W.V.D. and Crevel, R.V., 2007. The effect of type 2 diabetes mellitus on the presentation and treatment response of pulmonary tuberculosis. Clinical infectious diseases, 45(4), pp.428-435.

Historical Context and Re-Emergence: Diabetes mellitus (DM) was historically known as a risk factor for tuberculosis (TB) but gained less attention in the latter half of the 20th century with advancements in treatment. However, with the recent global increase in type 2 DM, the association between DM and TB has resurfaced, impacting 10%–30% of TB patients.

Epidemiological Data from Indonesia: Indonesia is ranked third worldwide for TB incidence and fourth for DM prevalence. Recent studies have highlighted the significant linkage between DM and TB within this demographic.

Impact of Insulin on TB Outcomes: Before the introduction of insulin in 1922, DM patients frequently succumbed to pulmonary TB. Although TB continues to pose a threat, the prognosis for DM patients has markedly improved with the advent of effective TB treatments.

Clinical Observations in Indonesia: A notable proportion of TB patients in Indonesia are diagnosed with type 2 DM. These patients present with more symptoms but without increased severity on TB diagnostic tests, suggesting a complex interaction rather than direct exacerbation by DM.

Treatment Dynamics and Outcomes: Diabetic patients with TB tend to adhere better to treatment protocols and show lower drug resistance rates. However, DM complicates the treatment outcome, evidenced by higher positive sputum culture rates after six months, even when accounting for other variables.

Recommendations for Dual Screening: Given the intertwined complications and symptoms of both diseases, it is recommended to screen all TB patients for DM, especially those over 35, to optimize management and improve treatment outcomes.

Type 2 diabetes mellitus and recurrent Tuberculosis

Alvarado-Valdivia, N.T., Flores, J.A., Inolopú, J.L. and Rosales-Rimache, J.A., 2024. Type 2 diabetes mellitus and recurrent Tuberculosis: A retrospective cohort in Peruvian military workers. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 35, p.100432.

·  The study of Type 2 Diabetes Mellitus (DM2) as a risk factor for Tuberculosis (TB) is complex due to:

• Population heterogeneity worldwide, including differences in age, access to medical care, level of glucose control, types and number of complications, and available medications. See also: https://tbreadingnotes.blogspot.com/2024/07/cost-effectiveness-and-resource.html

·  Findings from the study indicate:

• A higher prevalence of recurrent TB in military personnel with DM2 compared to those without DM2.
• A more rapid increase in cumulative risk for recurrent TB among patients with DM2.
• This suggests that military personnel diagnosed with DM2 may be more predisposed to recurrent TB. See also: https://tbreadingnotes.blogspot.com/2024/07/tuberculosis-in-healthcare-workers.html

·  Contextual factors to consider:

• In countries with limited to moderate resources, such as Peru, where both TB and DM2 are prevalent, military personnel with DM2 may be at increased risk due to fieldwork exposure. See also: https://tbreadingnotes.blogspot.com/2024/07/ambient-air-pollution-and-risk-of.html
• Despite these findings, the relationship between DM2 and recurrent TB in military personnel was not statistically significant.

·  Study limitations:

• The follow-up duration of three to nine months may have underestimated the recurrence rate. See also: https://tbreadingnotes.blogspot.com/2024/07/feasibility-of-achieving-2025-who.html

  

Loss to follow-up among adults with drug-resistant TB in PNG [TB0081]

Charles, F., Lin, Y.D., Greig, J., Gurra, S., Morikawa, R., Graham, S.M. and Maha, A., 2024. Loss to follow-up among adults with drug-resistant TB in Papua New Guinea. Public Health Action, 14(3), pp.85-90.

Papua New Guinea (PNG) is listed by WHO as one of 30 high-burden countries for TB and MDR/RR-TB.

TB incidence in PNG (2022) is 432 per 100,000 population, while MDR/RR-TB incidence is 22 per 100,000. See also: https://tbreadingnotes.blogspot.com/2024/09/tb-in-patients-with-hiv-and-diabetes.html

PNG is a middle-income country with 22 provinces, approximately 12 million people, and 80% of the population living in rural, often remote areas.

Around 75% of PNG’s population is under 35 years old, making younger people particularly vulnerable to TB. See also: https://tbreadingnotes.blogspot.com/2024/10/tb-treatment-and-resulting-abnormal.html

The treatment success rate for TB is approximately 50%, well below the national target of 90%.

Loss to follow-up (LTFU) is high at 22%, especially among people aged 15-34 years, and is linked to socioeconomic and geographic barriers, particularly in rural areas.

Young untreated patients are at risk of complications and contribute to the transmission of TB in the community. See also: https://tbreadingnotes.blogspot.com/2024/10/patient-health-system-population.html

LTFU is associated with difficult treatment regimens, including long durations, high pill burdens, toxic drugs, and painful injections over several months.

Remote populations face additional challenges, such as access to clinics for daily injections.

Decentralizing TB services and introducing rapid molecular diagnostics at the primary care level could improve access and coverage while maintaining treatment outcomes.

 

Effects of Xpert MTB/RIF and alternative diagnostics for TB in Tanzania [0078]

Langley, I., Lin, H.H., Egwaga, S., Doulla, B., Ku, C.C., Murray, M., Cohen, T. and Squire, S.B., 2014. Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach. The Lancet Global Health, 2(10), pp.e581-e591.

New diagnostic methods and algorithms could address weaknesses in current diagnostic processes but may increase resource and funding demands.

Full rollout of Xpert (B1) offers the greatest patient-level benefits among diagnostic options.

Xpert reduces the mean number of patient visits for diagnosis by 1.2 (95% CrI 1.1–1.3).

Time to start treatment decreases by 6.6 days (95% CrI 5.9–7.3) with Xpert.

Diagnostic loss to follow-up reduces by 7% (95% CrI 6–9), increasing successful diagnosis and treatment completion by 18%.

At the health-system level, full Xpert scale-up reduces required sputum samples by 34% (441,000 vs. 730,000 annually).

Xpert requires only 45% of the laboratory staff time compared to the base case.

Full Xpert rollout has the greatest epidemiological impact on reducing tuberculosis prevalence, mortality, and incidence.

Over 10 years, Xpert is projected to prevent 17,000 (95% CrI 8,800–26,600) tuberculosis cases and 39,700 (95% CrI 27,600–53,000) deaths.

New diagnostics also improve survival rates of tuberculosis and HIV co-infected patients, increasing ART access.

Three cost-effective strategies in Tanzania:

• Full Xpert MTB/RIF (B1) rollout at $169 per DALY averted.
• Same-day LED fluorescence microscopy (A3) at $45 per DALY averted.
• LED fluorescence microscopy (A2) at $29 per DALY averted.