An estimated one quarter of the world’s population have latent tuberculosis infection, of whom 5-10% will go on to develop TB disease at some stage. Screening and preventive treatment of latent tuberculosis infection is considered essential for global TB control. Children who have been in contact with a highly infectious tuberculosis case, and people with HIV have already been targeted for preventive treatment of LTBI. Another such high-risk group is people with diabetes in tuberculosis-endemic countries.
An estimated one quarter of the world’s population have latent tuberculosis infection, of whom 5-10% will go on to develop TB disease at some stage. Screening and preventive treatment of latent tuberculosis infection is considered essential for global TB control. Children who have been in contact with a highly infectious tuberculosis case, and people with HIV have already been targeted for preventive treatment of LTBI. Another such high-risk group is people with diabetes in tuberculosis-endemic countries.
We will perform the first randomized controlled trial globally to evaluate the efficacy and impact of preventive treatment of latent tuberculosis infection in people living with diabetes. We will randomize 3000 people with diabetes and latent tuberculosis in Tanzania and Uganda to a 12-week course of rifapentine and isoniazid preventive therapy or placebo, with cumulative incidence of tuberculosis disease over at least 24-months follow-up as primary endpoint.
"Globally, there are now an estimated 425 million people living with diabetes, but this number will increase significantly over the coming decades, especially in Sub-Saharan African countries such as Uganda and Tanzania."
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Prof. Reinout Van Crevel (Radboudumc, The Netherlands) and Dr. Irene Andia-Biraro (Makerere University, Uganda) presented at the 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), which took place as a hybrid event, both online and in Copenhagen-Denmark.
Prof. Reinout gave a talk on “Host-pathogen interactions and immunotherapy in mycobacterial infections” co-organised with the ESCMID Study Group for Mycobacterial Infections (ESGMYC), ESCMID Fungal Infection Study Group (EFISG), and ESCMID Study Group for Respiratory Viruses (ESGREV). The presentation focused on how antimicrobial therapies alone are insufficient to improve patient outcomes, as highlighted by the COVID-19 pandemic, underlining the relevance of host-pathogen interactions and immunotherapy in infectious diseases. The host response to the pathogen often causes collateral damage, and therapies are required to dampen these harmful responses. Recent advances show how new biomarkers or biosignatures can help direct immunotherapy to improve the outcome of sepsis, fungal infections, and mycobacterial disease. Such host-directed therapy is increasingly important in light of increasing antimicrobial resistance. Prof. Reinout’s session presented a state-of-the-art overview of host-pathogen interaction and immunotherapy in infectious diseases, linking laboratory sciences, clinical trials, and individual patients.
Dr. Irene Andia Biraro presentation focused on “Risk stratification for TB preventive therapy in high- and low-endemic settings” co-organised with the ESCMID Study Group for Mycobacterial Infections (ESGMYC). She addressed how screening for latent tuberculosis infection and preventive therapies are crucial for better control of global tuberculosis (TB) pandemic. Recent studies have brought breakthroughs in the understanding of TB infection and (subclinical) disease, new tests and biomarkers, better ways to predict individual risks for developing TB, and new preventive regimens. Dr. Bariro’s session during the conference symposium presented state-of-art progress in TB infection and preventive therapies; linking discovery science, epidemiology, policy, and clinical practice, with relevance to high- and low-TB-endemic settings.
The PROTID (Preventive Treatment of Latent Tuberculosis Infection in people with Diabetes Mellitus) project addresses a key EDCTP prevention priority area, namely TB and comorbidities. In 2022 we initiated the first randomized controlled trial globally that evaluates the efficacy and impact of preventive treatment of latent tuberculosis infection (LTBI) in people living with diabetes. On 27-28 February the PROTID consortium came together for the first face-to-face meeting since the COVID-19 pandemic in Moshi, Tanzania.
PROTID aims to enrol ~6000 people living with diabetes in Tanzania and Uganda in a large descriptive cohort, of which 3000 people with diabetes and LTBI will be randomised to a 12-week course of rifapentine and isoniazid preventive therapy or placebo, with cumulative incidence of TB disease over 24 months’ follow-up as the primary endpoint. 1000 people with diabetes but without evidence of LTBI will be followed in parallel to confirm whether their incidence of TB is too low to warrant preventive treatment.
So far, we have enrolled ~2000 participants in the diabetes cohort (of which ~50% LTBI positive), ~750 participants in the RCT, and another ~350 in the parallel cohort. We have also started collecting data on gaps in prevention and therapeutic management of combined TB and diabetes, as well as estimation of the population impact and cost-effectiveness of treatment of LTBI in people living with diabetes. The considerable cohort size enabled discussion of the first unique characteristics of the diabetes population in Sub-Saharan Africa (SSA) at this annual meeting. A framework for SSA PhD and MSc students has been successfully implemented, and also African leadership remains a continuous point of attention with half of the WPs being led by African PIs, as well as the RCT being led by NIMR-MMRC (Mbeya, Tanzania) as study sponsor.
At the annual meeting, the consortium discussed that irrespective of a steady recruitment pace throughout 2022/2023, we are lagging behind on our original project planning. We discussed alternative strategies for increasing recruitment rates at length. Potential strategies include opening of additional sites and slimming down supporting project activities. This is continuously balanced against overall project output and impact. Overall, the PROTID consortium convened in a highly inclusive atmosphere, and was determined to move forward in a positive direction.
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Follow our website and twitter for the latest news.
Prof. Reinout Van Crevel (Radboudumc, The Netherlands) and Dr. Irene Andia-Biraro (Makerere University, Uganda) presented at the 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), which took place as a hybrid event, both online and in Copenhagen-Denmark.
Prof. Reinout gave a talk on “Host-pathogen interactions and immunotherapy in mycobacterial infections” co-organised with the ESCMID Study Group for Mycobacterial Infections (ESGMYC), ESCMID Fungal Infection Study Group (EFISG), and ESCMID Study Group for Respiratory Viruses (ESGREV). The presentation focused on how antimicrobial therapies alone are insufficient to improve patient outcomes, as highlighted by the COVID-19 pandemic, underlining the relevance of host-pathogen interactions and immunotherapy in infectious diseases. The host response to the pathogen often causes collateral damage, and therapies are required to dampen these harmful responses. Recent advances show how new biomarkers or biosignatures can help direct immunotherapy to improve the outcome of sepsis, fungal infections, and mycobacterial disease. Such host-directed therapy is increasingly important in light of increasing antimicrobial resistance. Prof. Reinout’s session presented a state-of-the-art overview of host-pathogen interaction and immunotherapy in infectious diseases, linking laboratory sciences, clinical trials, and individual patients.
Dr. Irene Andia Biraro presentation focused on “Risk stratification for TB preventive therapy in high- and low-endemic settings” co-organised with the ESCMID Study Group for Mycobacterial Infections (ESGMYC). She addressed how screening for latent tuberculosis infection and preventive therapies are crucial for better control of global tuberculosis (TB) pandemic. Recent studies have brought breakthroughs in the understanding of TB infection and (subclinical) disease, new tests and biomarkers, better ways to predict individual risks for developing TB, and new preventive regimens. Dr. Bariro’s session during the conference symposium presented state-of-art progress in TB infection and preventive therapies; linking discovery science, epidemiology, policy, and clinical practice, with relevance to high- and low-TB-endemic settings.
The PROTID (Preventive Treatment of Latent Tuberculosis Infection in people with Diabetes Mellitus) project addresses a key EDCTP prevention priority area, namely TB and comorbidities. In 2022 we initiated the first randomized controlled trial globally that evaluates the efficacy and impact of preventive treatment of latent tuberculosis infection (LTBI) in people living with diabetes. On 27-28 February the PROTID consortium came together for the first face-to-face meeting since the COVID-19 pandemic in Moshi, Tanzania.
PROTID aims to enrol ~6000 people living with diabetes in Tanzania and Uganda in a large descriptive cohort, of which 3000 people with diabetes and LTBI will be randomised to a 12-week course of rifapentine and isoniazid preventive therapy or placebo, with cumulative incidence of TB disease over 24 months’ follow-up as the primary endpoint. 1000 people with diabetes but without evidence of LTBI will be followed in parallel to confirm whether their incidence of TB is too low to warrant preventive treatment.
So far, we have enrolled ~2000 participants in the diabetes cohort (of which ~50% LTBI positive), ~750 participants in the RCT, and another ~350 in the parallel cohort. We have also started collecting data on gaps in prevention and therapeutic management of combined TB and diabetes, as well as estimation of the population impact and cost-effectiveness of treatment of LTBI in people living with diabetes. The considerable cohort size enabled discussion of the first unique characteristics of the diabetes population in Sub-Saharan Africa (SSA) at this annual meeting. A framework for SSA PhD and MSc students has been successfully implemented, and also African leadership remains a continuous point of attention with half of the WPs being led by African PIs, as well as the RCT being led by NIMR-MMRC (Mbeya, Tanzania) as study sponsor.
At the annual meeting, the consortium discussed that irrespective of a steady recruitment pace throughout 2022/2023, we are lagging behind on our original project planning. We discussed alternative strategies for increasing recruitment rates at length. Potential strategies include opening of additional sites and slimming down supporting project activities. This is continuously balanced against overall project output and impact. Overall, the PROTID consortium convened in a highly inclusive atmosphere, and was determined to move forward in a positive direction.
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Another insightful publication from our consortium. This review highlights gaps in the incomplete understanding of the mechanisms that may relate to TB susceptibility in type 2 DM (T2DM). Understanding these three main domains regarding mechanisms of TB susceptibility in T2DM patients can help us build practical treatment plans to lessen the combined burden of the diseases in rampant areas.
Access the full text via the below link:
This project is part of the EDCTP2 programme supported by the European Union (grant number RIA2018CO-2514).
continue readingThis systematic review from our Ugandan PROTID colleagues demonstrates that the availability of essential medicines and diagnostic tests for diabetes in Africa is suboptimal. The relatively high cost of insulin, HbA1c, and lipid profile tests forms a significant barrier to optimal diabetes care. The article advocates pragmatic country-specific strategies to address these inequities in access and cost.
Access the full text via the below link:
This project is part of the EDCTP2 programme supported by the European Union (grant number RIA2018CO-2514).
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Another great PROTID collaboration: this systematic review and meta-analysis documented the proportion of attainment of optimal HbA1c, blood pressure and low-density lipoprotein cholesterol (LDLC) goals and the prevalence of five diabetes complications (diabetic peripheral neuropathy, nephropathy, retinopathy, foot ulcers and peripheral arterial disease) in adult native populations with type 2 diabetes in Africa. Please access the full text via this link:
This project is part of the EDCTP2 programme supported by the European Union (grant number RIA2018CO-2514).
continue readingIn June 2022 the first participants were enrolled in the PROTID study. After succesful Site Initiation Visits performed by the study Sponsor (NIMR-MMRC, Mbeya, TZA), all sites were able to start enrolment by June. See for a full description of the study protocol: Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial | Trials | Full Text (biomedcentral.com)
Trial activities in Kampala (Uganda):
@PROTID