A digital health algorithm to guide antibiotic prescription in pediatric outpatient care: a cluster randomized controlled trial

Rainer Tan, Godfrey Kavishe, Lameck B. Luwanda, Alexandra V. Kulinkina, Sabine Renggli, Chacha Mangu, Geofrey Ashery, Margaret Jorram, Ibrahim Evans Mtebene, Peter Agrea, Humphrey Mhagama, Alan Vonlanthen, Vincent Faivre, Julien Thabard, Gillian Levine, Marie-Annick Le Pogam, Kristina Keitel, Patrick Taffé, Nyanda Ntinginya, Honorati Masanja & Valérie D’Acremont

Excessive antibiotic use and antimicrobial resistance are major global public health threats. We developed ePOCT+, a digital clinical decision support algorithm in combination with C-reactive protein test, hemoglobin test, pulse oximeter and mentorship, to guide health-care providers in managing acutely sick children under 15 years old. To evaluate the impact of ePOCT+ compared to usual care, we conducted a cluster randomized controlled trial in Tanzanian primary care facilities. Over 11 months, 23,593 consultations were included from 20 ePOCT+ health facilities and 20,713 from 20 usual care facilities. The use of ePOCT+ in intervention facilities resulted in a reduction in the coprimary outcome of antibiotic prescription compared to usual care (23.2% versus 70.1%, adjusted difference −46.4%, 95% confidence interval (CI) −57.6 to −35.2). The coprimary outcome of day 7 clinical failure was noninferior in ePOCT+ facilities compared to usual care facilities (adjusted relative risk 0.97, 95% CI 0.85 to 1.10). There was no difference in the secondary safety outcomes of death and nonreferred secondary hospitalizations by day 7. Using ePOCT+ could help address the urgent problem of antimicrobial resistance by safely reducing antibiotic prescribing.

Published at:  2023-12-18

A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis

Authors: A Dierig, M Hoelscher, S Schultz, L Hoffmann, A Jarchow-MacDonald, EM Svensson, L Te Brake, R Aarnoutse, M Boeree, TD McHugh, LM Wildner, X Gong, PPJ Phillips, LT Minja, N Ntinginya, S Mpagama, A Liyoyo, RS Wallis, M Sebe, FA Mhimbira, B Mbeya, M Rassool, L Geiter, YL Cho & N Heinrich

Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure–response and exposure–toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin.

Published at:  2023-06-06

Unravelling patient pathways in the context of antibacterial resistance in East Africa

Authors: Katherine Keenan1*, Kathryn J. Fredricks1, Mary Abed Al Ahad1, Stella Neema2, Joseph R. Mwanga3,Mike Kesby1, Martha F. Mushi3, Annette Aduda4, Dominique L. Green1, Andy G. Lynch1, Sarah I. Huque1,Blandina T. Mmbaga5, Hannah Worthington1, Catherine Kansiime2, Emmanuel Olamijuwon1,Nyanda E. Ntinginya6, Olga Loza1, Joel Bazira7, Antonio Maldonado‑Barragán1, VAnne Smith1,Arun Gonzales Decano1, John Mwaniki Njeru4, Alison Sandeman1, John Stelling8, Alison Elliott9,10,David Aanensen11, Stephen H. Gillespie1, Gibson Kibiki12, Wilber Sabiiti1, Derek J. Sloan1, Benon B. Asiimwe2,John Kiiru4, Stephen E. Mshana3, Matthew T. G. .

A key factor driving the development and maintenance of antibacterial resistance (ABR) is individuals’use of antibiotics (ABs) to treat illness. To better understand motivations and context for antibiotic use we use theconcept of a patient treatment‑seeking pathway: a treatment journey encompassing where patients go when theyare unwell, what motivates their choices, and how they obtain antibiotics. This paper investigates patterns and deter‑minants of patient treatment‑seeking pathways, and how they intersect with AB use in East Africa, a region whereABR‑attributable deaths are exceptionally high ........

Published at:  2023-06-01

“Honestly, this problem has affected me a lot”: a qualitative exploration of the lived experiences of people with chronic respiratory disease in Sudan and Tanzania

Authors: Uzochukwu Egere, Elizabeth H Shayo, Martha Chinouya, Miriam Taegtmeyer, Jane Ardrey, Stellah Mpagama, Nyanda Elias Ntinginya, Rana Ahmed, El Hafiz Hussein, Asma El Sony, Tom Wingfield, Angela Obasi, Rachel Tolhurst & The IMPALA Consortium

Over 500 million people live with chronic respiratory diseases globally and approximately 4 million of these, mostly from the low- and middle-income countries including sub-Saharan Africa, die prematurely every year. Despite high CRD morbidity and mortality, only very few studies describe CRDs and little is known about the economic, social and psychological dimensions of living with CRDs in sub-Saharan Africa. We aimed to gain an in-depth understanding of the social, livelihood and psychological dimensions of living with CRD to inform management of CRDs in Sudan and Tanzania.

Published at:  2023-03-13

A practical approach to render tuberculosis samples safe for application of tuberculosis molecular bacterial load assay in clinical settings without a biosafety level 3 laboratory

Authors: Bariki Mtafya a b, Paschal Qwaray a, Joseph John a, Emanuel Sichone a, Alice Shoo a, Stephen H. Gillespie b, Nyanda Elias Ntinginya a, Wilber Sabiiti

Mycobacterium tuberculosis is a category B infectious pathogen requiring level-3-containment laboratories for handling. We assessed the efficacy of heat and Guanidine thiocyanate (GTC) to inactivate M. tuberculosis prior to performance of tuberculosis Molecular Bacterial Load Assay (TB-MBLA).

Published at:  2023-02-16

Systematic comparison of HIV-1 Envelope-specific IgG responses induced by different vaccination regimens: Can we steer IgG recognition towards regions of viral vulnerability?

Authors: Augusta Horvath1,2, Lisa Rogers1,2, Georgios Pollakis3, Olga Baranov1,2, Nora Pieroth1,2, Sarah Joseph4, Mkunde Chachage5, Asli Heitzer1, Lucas Maganga5, Frank Msafiri6, Agricola Joachim6, Edna Viegas7, Leigh-Anne Eller8,9,10, Hannah Kibuuka9, Supachai Rerks-Ngarm11, Punnee Pitisuttithum12, Sorachai Nitayapan13, Jittima Dhitavat12, Nakorn Premsri11, Sarah Fidler14, Robin J. Shattock14, Merlin Lee Robb8,10, Jonathan Weber14, Sheena McCormack4, Patricia Jane Munseri6, Eligius Lyamuya6, Charlotta Nilsson15,16, Arne Kroidl1,2, Michael Hoelscher1,2, Ralf Wagner17,18, Christof Geldmacher1,2† and Kathrin Held1,2†*

Immunogens and vaccination regimens can influence patterns of immune-epitope recognition, steering them towards or away from epitopes of potential viral vulnerability. HIV-1 envelope (Env)-specific antibodies targeting variable region 2 (V2) or 3 (V3) correlated with protection during the RV144 trial, however, it was suggested that the immunodominant V3 region might divert antibody responses away from other relevant sites. We mapped IgG responses against linear Env epitopes in five clinical HIV vaccine trials, revealing a specific pattern of Env targeting for each regimen. Notable V2 responses were only induced in trials administering CRF01_AE based immunogens, but targeting of V3 was seen in all trials, with the soluble, trimeric CN54gp140 protein eliciting robust V3 recognition. Strong V3 targeting was linked to greater overall respons...........

Published at:  2023-01-09

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