The relentless spread of tuberculosis in Zambia - trends over the past 37 years (1964- 2000)

Objective. To review trends in the rates of tuberculosis (TB) case notifications over a 37-year period.Design. A retrospective study of Ministry of Health records on TB notifications between 1 January 1964 and 31 December 2000.Setting. Zambia, sub-Saharan Africa.Methods. Retrospective analysis of case-notification data for TB of the Zambia Ministry of Health annual returns.Outcome measures. Annual TB case-notification rates and trends over the past 37 years.Results. TB case-notification data from 1964 to 2000 show a 12-fold increase over the past two decades, and apparent gains in controlling TB seen in the 1960s and 1970s have been reversed over the past two decades. A stable situation during the period 1964 - 1984 (case-notification rate remained around 100 per 100 000 population) was followed by an exponential increase since the mid-1980s. The absolute number of new TBcases increased from 8 246 in 1985 (124/100 000) to 38 863 (409/100 000) in 1996 and 52 000 (512/100 000) in 2000. Comparison of case-notification rates over the past 2 decades with neighbouring countries (Zimbabwe, Malawi and Tanzania) show that Zambia has one of the highest case notification rates in the region.Conclusions. Zambia, like many countries in Africa, is in the midst of a serious TB epidemic and there are no signs that it is abating. This increase was most likely due to the impact of the HIV / AIDS epidemic and subsequent breakdown of TB services. Concerted donor-government efforts should invest appropriately in long-term plans for TB control

Developing a model for decision-making around antibiotic prescribing for patients with COVID-19 pneumonia in acute NHS hospitals during the first wave of the COVID-19 pandemic: Qualitative results from the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients (PEACH Study)

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Objective To explore and model factors affecting antibiotic prescribing decision-making early in the pandemic. Design Semistructured qualitative interview study. Setting National Health Service (NHS) trusts/health boards in England and Wales. Participants Clinicians from NHS trusts/health boards in England and Wales. Method Individual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions. Results During the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed. Conclusion This study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic. Trial registration number ISRCTN66682918

Low-dose vitamin D3 supplementation does not affect natural regulatory T cell population but attenuates seasonal changes in T cell-produced IFN-γ: Results from the D-SIRe2 randomised controlled trial

Background: Seasonal variations have been reported for immune markers. However, the relative contributions of sunlight and vitamin D variability on such seasonal changes are unknown. Objective: This double-blind, randomized, placebo-controlled trial tested whether daily 400 IU vitamin D3 supplementation affected short-term (12 weeks) and long-term (43 weeks) natural regulatory T cell (nTreg) populations in healthy participants. Design: 62 subjects were randomized equally to vitamin D versus placebo in March and assessed at baseline, April (4w), June (12w), September (25w) and January (43w). Circulating nTregs, ex vivo proliferation, IL-10 and IFN-γ productions were measured. Vitamin D metabolites and sunlight exposure were also assessed. Results: Mean serum 25-hydroxyvitamin D (25(OH)D) increased from 35.8(SD 3.0) to 65.3(2.6) nmol/L in April and remained above 70 nmol/L with vitamin D supplementation, whereas it increased from 36.4(3.2) to 49.8(3.5) nmol/L in June to fall back to 39.6(3.5) nmol/L in January with placebo. Immune markers varied similarly between groups according to the season, but independently of 25(OH)D. For nTregs, the mean (%CD3+CD4+CD127lo cells (SEM)) nadir observed in March (2.9(0.1)%) peaked in September at 4.0(0.2)%. Mean T cell proliferation peaked in June (33156(1813) CPM) returning to the nadir in January (17965 (978) CPM), while IL-10 peaked in June and reached its nadir in September (median (IQR) of 262(283) to (121(194) pg/ml, respectively). Vitamin D attenuated the seasonal increase in IFN-γ by ~28% with mean ng/ml (SEM) for placebo vs vitamin D, respectively, for April 12.5(1.4) vs 10.0(1.2) (p=0.02); June 13.9(1.3) vs 10.2(1.7) (p=0.02) and January 7.4(1.1) vs 6.0(1.1) (p=0.04). Conclusions: Daily low dose Vitamin D intake did not affect the nTregs population. There were seasonal variation in nTregs, proliferative response and cytokines, suggesting that environmental changes influence immune response, but the mechanism seems independent of vitamin D status. Vitamin D attenuated the seasonal change in T cell-produced IFN-γ, suggesting a decrease in effector response which could be associated with inflammation. Clinical trial identifier: ISRCTN 73114576 (https://www.isrctn.com

The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study

\ua9 The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.Background: Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. Objectives: Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. Methods: Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a \ua320000/QALY threshold. Uncertainty was characterized using bootstrapping. Results: People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups’ 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (\ua39830 versus \ua310 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. Conclusions: Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty

Procalcitonin evaluation of antibiotic use in COVID-19 hospitalised patients (PEACH): protocol for a retrospective observational study

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health. Procalcitonin (PCT) is an inflammatory marker measured in blood samples and widely recommended to help diagnose bacterial infections and guide antibiotic treatment. The PEACH study will compare patient outcomes from English and Welsh hospitals that used PCT testing during the first wave of the COVID-19 pandemic with those from hospitals not using PCT. It will help to determine whether, and how, PCT testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. PEACH is a retrospective observational cohort study using patient-level clinical data from acute hospital Trusts and Health Boards in England and Wales. The primary objective is to measure the difference in antibiotic use between COVID-19 patients who did or did not have PCT testing at the time of diagnosis. Secondary objectives include measuring differences in length of stay, mortality, intensive care unit admission, and resistant bacterial infections between these groups

A retrospective propensity-score-matched cohort study of the impact of procalcitonin testing on antibiotic use in hospitalized patients during the first wave of COVID-19.

BackgroundProcalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK.ObjectivesPrimary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups.MethodsMulti-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020.ResultsData from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22-0.64 days, P ConclusionsBaseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility.Study registration numberISRCTN66682918

The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study

Background Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. Objectives Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. Methods Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. Results People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups’ 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. Conclusions Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty

The relentless spread of tuberculosis in Zambia - trends over the past 37 years (1964-2000)

Objective. To review trends in the rates of tuberculosis (TB) case notifications over a 37-year period. Design. A retrospective study of Ministry of Health records on TB notifications between I January 1964 and 31 December 2000. Setting. Zambia, sub-Saharan Africa. Methods. Retrospective analysis of case-notification data for TB of the Zambia Ministry of Health annual returns. Outcome measures. Annual TB case-notification rates and trends over the past 37 years. Results. TB case-notification data from 1964 to 2000 show a 12-fold increase over the past two decades, and apparent gains in controlling TB seen in the 1960s and 1970s have been reversed over the past two decades. A stable situation during the period 1964-1984 (case-notification rate remained around 100 per 100 000 population) was followed by an exponential increase since the mid-1980s. The absolute number of new TB cases increased from 8 246 in 1985 (124/100 000) to 38 863 (409/100 000) in 1996 and 52 000 (512/100 000) in 2000. Comparison of case-notification rates over the past 2 decades with neighbouring countries (Zimbabwe, Malawi and Tanzania) show that Zambia has one of the highest case-notification rates in the region. Conclusions. Zambia, like many countries in Africa, is in the midst of a serious TB epidemic and there are no signs that it is abating. This increase was most likely due to the impact of the HIV/AIDS epidemic and subsequent breakdown of TB services. Concerted donor-government efforts should invest appropriately in long-term plans for TB control

The potential to expand antiretroviral therapy by improving health facility efficiency: evidence from Kenya, Uganda, and Zambia

Background Since 2000, international funding for HIV has supported scaling up antiretroviral therapy (ART) in sub-Saharan Africa. However, such funding has stagnated for years, threatening the sustainability and reach of ART programs amid efforts to achieve universal treatment. Improving health system efficiencies, particularly at the facility level, is an increasingly critical avenue for extending limited resources for ART; nevertheless, the potential impact of increased facility efficiency on ART capacity remains largely unknown. Through the present study, we sought to quantify facility-level technical efficiency across countries, assess potential determinants of efficiency, and predict the potential for additional ART expansion. Methods Using nationally-representative facility datasets from Kenya, Uganda and Zambia, and measures adjusting for structural quality, we estimated facility-level technical efficiency using an ensemble approach that combined restricted versions of Data Envelopment Analysis and Stochastic Distance Function. We then conducted a series of bivariate and multivariate regression analyses to evaluate possible determinants of higher or lower technical efficiency. Finally, we predicted the potential for ART expansion across efficiency improvement scenarios, estimating how many additional ART visits could be accommodated if facilities with low efficiency thresholds reached those levels of efficiency. Results In each country, national averages of efficiency fell below 50 % and facility-level efficiency markedly varied. Among facilities providing ART, average efficiency scores spanned from 50 % (95 % uncertainty interval (UI), 48–62 %) in Uganda to 59 % (95 % UI, 53–67 %) in Zambia. Of the facility determinants analyzed, few were consistently associated with higher or lower technical efficiency scores, suggesting that other factors may be more strongly related to facility-level efficiency. Based on observed facility resources and an efficiency improvement scenario where all facilities providing ART reached 80 % efficiency, we predicted a 33 % potential increase in ART visits in Kenya, 62 % in Uganda, and 33 % in Zambia. Given observed resources in facilities offering ART, we estimated that 459,000 new ART patients could be seen if facilities in these countries reached 80 % efficiency, equating to a 40 % increase in new patients. Conclusions Health facilities in Kenya, Uganda, and Zambia could notably expand ART services if the efficiency with which they operate increased. Improving how facility resources are used, and not simply increasing their quantity, has the potential to substantially elevate the impact of global health investments and reduce treatment gaps for people living with HIV