Vitamin D status in tuberculosis patients with diabetes, prediabetes and normal blood glucose in China: a cross-sectional study.

OBJECTIVE: The association between tuberculosis (TB), diabetes mellitus (DM) and vitamin D status is poorly characterised. We therefore: (1) determined vitamin D status in patients with TB in relation to whether they had normal fasting blood glucose (FBG), pre-DM or DM and (2) assessed whether baseline characteristics in patients with TB, including their DM status, were associated with vitamin D deficiency. METHODS: In patients with TB consecutively attending six clinics or hospitals in China, we measured 25-hydroxycholecalciferol (25-(OH)D3) at the time of registration using electrochemiluminescence in a COBASE 601 Roche analyser by chemiluminescence immunoassay. Data analysis was performed using the χ2 test, ORs and multivariate logistic regression. RESULTS: There were 306 eligible patients with TB, including 96 with smear positive pulmonary TB, 187 with smear negative pulmonary TB and 23 with extrapulmonary TB. Of these, 95 (31%) had normal blood glucose, 83 (27%) had pre-DM and 128 (42%) had DM. Median serum vitamin D levels were 16.1 ng/mL in patients with TB with normal FBG, 12.6 ng/mL in patients with TB with pre-DM and 12.1 ng/mL in patients with TB with DM (p<0.001). The study highlighted certain baseline characteristics associated with vitamin D deficiency (25-(OH)D3<20 ng/mL). After adjusting for confounders, serum vitamin D deficiency was significantly more common in patients being registered in the cold season (November to April) (p=0.006) and in those with DM (p=0.003). CONCLUSION: Vitamin D levels are lower in patients with TB with pre-DM and DM and are also affected by certain baseline characteristics that include being registered in the cold season and having DM. TB programmes need to pay more attention to vitamin D status in their patients, especially if there is coexisting pre-DM or DM

What can National TB Control Programmes in low- and middle-income countries do to end tuberculosis by 2030?

The international community has committed to ending the tuberculosis (TB) epidemic by 2030. This will require multi-sectoral action with a focus on accelerating socio-economic development, developing and implementing new tools, and expanding health insurance coverage. Within this broad framework, National TB Programmes (NTPs) are accountable for delivering diagnostic, treatment, and preventive services. There are large gaps in the delivery of these services, and the aim of this article is to review the crucial activities and interventions that NTPs must implement in order to meet global targets and milestones that will end the TB epidemic. The key deliverables are the following: turn End TB targets and milestones into national measurable indicators to make it easier to track progress; optimize the prompt and accurate diagnosis of all types of TB; provide rapid, complete, and effective treatment to all those diagnosed with TB; implement and monitor effective infection control practices; diagnose and treat drug-resistant TB, associated HIV infection, and diabetes mellitus; design and implement active case finding strategies for high-risk groups and link them to the treatment of latent TB infection; engage with the private-for-profit sector; and empower the Central Unit of the NTP particularly in relation to data-driven supportive supervision, operational research, and sustained financing. The glaring gaps in the delivery of TB services must be remedied, and some of these gaps will require new paradigms and ways of working which include patient-centered and higher-quality services. There must also be fast-track ways of incorporating new diagnostic, treatment, and prevention tools into program activities so as to rapidly reduce TB incidence and mortality and meet the goal of ending TB by 2030

Declining Trends in Childhood TB Notifications and Profile of Notified Patients in the City of Harare, Zimbabwe, from 2009 to 2018.

Globally, childhood tuberculosis (TB among those aged <15 years) is a neglected component of national TB programmes in high TB burden countries. Zimbabwe, a country in southern Africa, is a high burden country for TB, TB-HIV, and drug-resistant TB. In this study, we assessed trends in annual childhood TB notifications in Harare (the capital of Zimbabwe) from 2009 to 2018 and the demographic, clinical profiles, and treatment outcomes of childhood TB patients notified from 2015-2017 by reviewing the national TB programme records and reports. Overall, there was a decline in the total number of TB patients (all ages) from 5,943 in 2009 to 2,831 in 2018. However, the number of childhood TB patients had declined exponentially 6-fold from 583 patients (117 per 100,000 children) in 2009 to 107 patients (18 per 100,000 children) in 2018. Of the 615 childhood TB patients notified between 2015 and 2017, 556 (89%) patient records were available. There were 53% males, 61% were aged <5 years, 92% were new TB patients, 85% had pulmonary TB, and 89% were treated for-drug sensitive TB, 3% for drug-resistant TB, and 40% were HIV positive (of whom 59% were on ART). Although 58% had successful treatment outcomes, the treatment outcomes of 40% were unknown (not recorded or not evaluated), indicating severe gaps in TB care. The disproportionate decline in childhood TB notifications could be due to the reduction in the TB burden among HIV positive individuals from the scale up of antiretroviral therapy and isoniazid preventive therapy. However, the country is experiencing economic challenges which could also contribute to the disproportionate decline in childhood TB notification and gaps in quality of care. There is an urgent need to understand the reasons for the declining trends and the gaps in care

Bacteriologically confirmed pulmonary tuberculosis patients: Loss to follow-up, death and delay before treatment initiation in Bulawayo, Zimbabwe from 2012–2016

Objective: To quantify and assess trends and risk factors for loss to follow-up (LTFU) and delays before treatment initiation among bacteriologically confirmed pulmonary tuberculosis (TB) patients (laboratory-diagnosed) in Bulawayo, 2012–16. Design: Cohort study using secondary programme data. Presumptive TB patients’ sputum samples were sent to the laboratory from the 19 primary health care clinics. Laboratory-diagnosed patients (microscopy or Xpert MTB/RIF) were tracked for treatment registration at the clinics. Results: Of 2443 laboratory-diagnosed patients, the mean (standard deviation, SD) delay from sputum receipt at the laboratory to testing was 2.7(1.6) days and from testing to result dispatch was 8.8(5.8) days. A total of 508(20.8%) were LTFU which included 252(10.3%) deaths. While the number of laboratory-diagnosed patients reduced over years, there was a significant increase in pre-treatment LTFU and death. Independent predictors of pre-treatment LTFU were age above 65 years, male gender and HIV positive/unknown. In addition, delay (≥3 days) between sputum receipt and testing was significantly associated with pre-treatment death. Among registered patients (n = 1935), the mean (SD) delay to initiate treatment was 29.1 (21.6) days which significantly declined over the years. Patients registered as new TB had significantly long treatment delay. Conclusions: Interventions to mitigate the risk factors for high loss to follow-up, deaths and delays before TB treatment are urgently required. Keywords: Tuberculosis/diagnosis, Tuberculosis/treatment, Early diagnosis, SORT IT, Operational research, Pre-diagnosis attrition, Pre-treatment attrition, Diagnosis and treatment cascad

How Can Operational Research Help to Eliminate Tuberculosis in the Asia Pacific Region?

Broad multi-sectoral action is required to end the tuberculosis (TB) epidemic by 2030 and this includes National TB Programmes (NTPs) fully delivering on quality-assured diagnostic, treatment and preventive services. Large implementation gaps currently exist in the delivery of these services, which can be addressed and closed through the discipline of operational research. This paper outlines the TB disease burden and disease-control programme implementation gaps in the Asia-Pacific region; discusses the key priority areas in diagnosis, treatment and prevention where operational research can be used to make a difference; and finally provides guidance about how best to embed operational research within a TB programme setting. Achieving internationally agreed milestones and targets for case finding and treatment requires the NTP to be streamlined and efficient in the delivery of its services, and operational research provides the necessary evidence-based knowledge and support to allow this to happen

An Opportunity to END TB: Using the Sustainable Development Goals for Action on Socio-Economic Determinants of TB in High Burden Countries in WHO South-East Asia and the Western Pacific Regions

The progress towards ending tuberculosis (TB) by 2035 is less than expected in 11 high TB burden countries in the World Health Organization South-East Asia and Western Pacific regions. Along with enhancing measures aimed at achieving universal access to quality-assured diagnosis, treatment and prevention services, massive efforts are needed to mitigate the prevalence of health-related risk factors, preferably through broader actions on the determinants of the “exposure-infection-disease-adverse outcome” spectrum. The aim of this manuscript is to describe the major socio-economic determinants of TB and to discuss how there are opportunities to address these determinants in an englobing manner under the United Nations Sustainable Development Goals (SDGs) framework. The national TB programs must identify stakeholders working on the other SDGs, develop mechanisms to collaborate with them and facilitate action on social-economic determinants in high TB burden geographical areas. Research (to determine the optimal mechanisms and impact of such collaborations) must be an integral part of this effort. We call upon stakeholders involved in achieving the SDGs and End TB targets to recognize that all goals are highly interlinked, and they need to combine and complement each other’s efforts to end TB and the determinants behind this disease

Tuberculosis Case Finding Cascade and Treatment Outcomes among Male Inmates in Two Prisons in Zimbabwe

Setting. Zimbabwe is a high tuberculosis (TB) burden country, with an estimated prevalence of 344/100,000 population. Though prisons are known high-prevalence sites for TB, the paucity of data affects the quantification of the disease and treatment outcomes in these settings. We measured the prevalence of TB disease and treatment outcomes among inmates at two major prisons in Harare, Zimbabwe. Design. A cohort study using programmatic data was undertaken to assess TB diagnostic cascade in one of the study prisons for 2018. Treatment outcomes among male inmates with TB were assessed over a period of four years, in two study prisons. Results. A total of 405 (11%) inmates with presumptive TB were identified, and 370 (91%) of these were evaluated for TB, mostly using rapid molecular testing of sputum specimens. Twenty-five inmates were diagnosed with TB resulting in a prevalence of 649/100,000 population. Of these, 16 (64%) were started on treatment. Nine (36%) were lost to follow-up before treatment initiation. From 2015 to 2018, 280 adult male inmates with TB were started on treatment. Of these, 212 (76%) had pulmonary disease that was bacteriologically confirmed. Almost all (276/280, 99%) had known HIV status, 65% were HIV-infected, and 80% of these were on antiretroviral treatment. The TB treatment success rate (cured or treatment completed) was recorded for 209 (75%) inmates, whilst 14 (5%) died and 11 (4%) were lost to follow-up. The frequency of unfavourable treatment outcomes (death, lost to follow-up, and not evaluated) was higher (54%) among inmates≥60 years than those in the age group of 45-59 years (17%). Conclusion. The findings revealed a threefold burden of TB in prisons, compared with what is reported by national survey. To decrease transmission of TB bacilli, it is essential to promote efforts that address missed opportunities in the TB diagnostic cascade, prompt treatment initiation, and ensure that tracking and documentation of treatment outcomes for all inmates are intensified

S1 File for "Vitamin D status of tuberculosis patients with diabetes mellitus in different economic areas and associated factors in China"

Vitamin D could be a mediator in the association between tuberculosis (TB) and diabetes mellitus (DM). A large scale multi-center study confirmed that TB patients with DM had significantly lower serum vitamin D level compared with those without DM and reported that DM was a strong independent risk factor for vitamin D deficiency. This study was undertaken to determine amongst patients with both TB and DM living in different economically defined areas in China: i) their baseline characteristics, ii) their vitamin D status and iii) whether certain baseline characteristics were associated with vitamin D deficiency. In DM-TB patients consecutively attending seven clinics or hospitals, we measured 25 hydroxycholecalciferol at the time of registration using electrochemiluminescence in a COBASE 601 Roche analyser by chemiluminescence immunoassay. Data analysis was performed using chi square test and multivariate logistic regression. There were 178 DM-TB patients that included 50 from economically well-developed areas, 103 from better-off areas and 25 from a poverty area. Median vitamin D levels in well-developed, better-off and poverty areas were 11.5ng/ml, 12.2ng/ml and 11.5ng/ml respectively. Amongst all patients, 149 (84%) had vitamin D deficiency-91 (51%) with vitamin D deficiency (10-19.9 ng/ml) and 58 (33%) with severe deficiency (&lt; 10 ng/ml). There was a significantly higher proportion with vitamin D deficiency in the poverty area. The adjusted odds of vitamin D deficiency (25-(OH)D3 &lt;20 ng/ml) were significantly higher in those with longer history of DM (P = 0.038) and with HbA1c≥10% (P = 0.003). Over 80% of TB patients with DM in China were vitamin D deficient, with risk factors being residence in a poverty area, a long duration of DM and uncontrolled DM. TB programme managers and clinicians need to pay more attention to the vitamin D status of their patients