Search

Introduction: Antimicrobial resistance (AMR) is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In sub-Saharan Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite rising prevalence of 3GCR-E, the health-impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GCR-E bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of AMR by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either third-generation cephalosporin susceptible (3GC-S) or third-generation resistant (3GC-R) Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. The primary outcomes for the study are mortality and morbidity from 3GCR-E. Healthcare economic outcomes will be assessed by comparing healthcare provider costs, indirect patient costs and health-related quality of life outcomes in patients with 3GC-S and 3GC-R BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient’s clinical presentation. Each BSI episode will be classified into the following categories: definite Gram-negative sepsis, probable Gram-negative sepsis, transient or occult bacteraemia, or contaminated blood culture. These classifications will be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee.

Background: Patients with tuberculosis (TB) symptoms in low-resource settings face convoluted diagnostic and treatment linkage pathways, incurring substantial health-seeking costs. In the context of a randomised trial looking at the impact of novel diagnostics such as computer-aided chest x-ray diagnosis (CAD4TB), we aimed to investigate the costs incurred by patients seeking TB diagnosis and whether optimised diagnostic interventions could result in a reduction in the cost faced by households. Methods: PROSPECT was a three-arm randomised trial conducted in a public primary health clinic in Blantyre, Malawi during 2018-2019 (trial arms: standard of care [SOC]; HIV testing [HIV]; HIV testing and CAD4TB [HIV/TB]). The direct and indirect costs incurred by 219 PROSPECT participants over the 56-day follow-up period were collected. Costs were deemed catastrophic if they exceeded 20% of annual household income. We compared mean costs and used generalised linear regression models to examine whether the interventions could result in a reduction in total costs. Results: The mean total cost incurred by all 219 participants was US$12.11 (standard error (SE): 1.86). The indirect and direct cost was US$8.47 (SE: 1.66) and US$3.64 (SE: 0.38), respectively. The mean total cost composed of 5.6% of the average annual household income. In total, 5% (9/180) of the participants with complete income data Open Peer Review Reviewer Status AWAITING PEER REVIEW Any reports and responses or comments on the article can be found at the end of the article. Page 1 of 13 Wellcome Open Research 2021, 6:153 Last updated: 02 JUL 2021 Corresponding author: Wala Kamchedzera (wala.kamchedzera@gmail.com) Author roles: Kamchedzera W: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Maheswaran H: Conceptualization, Methodology, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Squire SB: Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Joekes E: Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Pai M: Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Nliwasa M: Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; G Lalloo D: Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Webb EL: Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Corbett EL: Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; MacPherson P: Conceptualization, Funding Acquisition, Methodology, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests: No competing interests were disclosed. Grant information: PM was supported by the Wellcome Trust (grant number: WT206575). WK was supported by Wellcome (grant number: 218333/Z/19/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2021 Kamchedzera W et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original data is properly cited. How to cite this article: Kamchedzera W, Maheswaran H, Squire SB et al. Economic costs of accessing tuberculosis (TB) diagnostic services in Malawi: an analysis of patient costs from a randomised controlled trial of computer-aided chest x-ray interpretation [version 1; peer review: awaiting peer review] Wellcome Open Research 2021, 6:153 https://doi.org/10.12688/wellcomeopenres.16683.1 First published: 15 Jun 2021, 6:153 https://doi.org/10.12688/wellcomeopenres.16683.1 incurred catastrophic costs. Compared to SOC, there was no statistically significant difference in the mean total cost faced by those in the HIV (ratio: 0.77, 95% CI: 0.51, 1.19) and HIV/TB arms (ratio: 0.85, 95% CI: 0.53, 1.37). Conclusions: Despite the absence of user fees, patients seeking healthcare with TB symptoms incurred catastrophic costs. The optimised TB diagnostic interventions that were investigated in the PROSPECT study did not significantly reduce costs. TB diagnosis interventions should be implemented alongside social protection policies whilst ensuring healthcare facilities are accessible by the poor

Background: HIV-associated cryptococcal meningitis accounts for 15% of AIDS related deaths globally. In sub-Saharan Africa, acute mortality ranges from 24% to 100%. In addition to the mortality directly associated with cryptococcosis, patients with HIV-associated cryptococcal meningitis are at risk of a range of opportunistic infections (OIs) and hospital acquired nosocomial infections (HAIs). The attributable mortality associated with co-prevalent infections in cryptococcal meningitis has not been evaluated. Methods: As part of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) trial, consecutive HIV-positive adults with cryptococcal meningitis were randomised to one of five anti-fungal regimens and followed up until 10-weeks. We conducted a retrospective case note review of ACTA participants recruited from Queen Elizabeth Central Hospital in Blantyre, Malawi to describe the range and prevalence of OIs and HAIs diagnosed, and the attributable mortality associated with these infections. Results: We describe the prevalence of OIs and HAIs in 226 participants. Baseline median CD4 count was 29 cell/mm3, 57% (129/226) were on anti-retroviral therapy. 56% (127/226) had at least one co-prevalent infection during the 10-week study period. Data were collected for 187 co-prevalent infection episodes. Suspected blood stream infection was the commonest co-prevalent infection diagnosed (34/187, 18%), followed by community-acquired pneumonia (32/187, 17%), hospital-acquired pneumonia (13/187, 7%), pulmonary tuberculosis (12/187, 6%) and confirmed blood stream infections (10/187, 5%). All-cause mortality at 10-weeks was 35% (80/226), diagnosis of an OI or HAI increased the risk of death at 10 weeks by nearly 50% (HR 1.48, 95% CI 1.01-2.17, p=0.04). Conclusion: We demonstrate the high prevalence and broad range of OIs and HAIs occurring in patients with HIV-associated cryptococcal meningitis. These co-prevalent infections are associated with a significantly increased risk of death. Whether a protocolised approach to improve surveillance and proactive treatment of co-prevalent infections would improve cryptococcal meningitis outcomes warrants further investigation.

Background: Adults seeking diagnosis and treatment for tuberculosis (TB) and HIV in low-resource settings face considerable barriers and have high pre-treatment mortality. Efforts to improve access to prompt TB treatment have been hampered by limitations in TB diagnostics, with considerable uncertainty about how available and new tests can best be implemented. Design and methods: The PROSPECT Study is an open, three-arm pragmatic randomised study that will investigate the effectiveness and cost-effectiveness of optimised HIV and TB diagnosis and linkage to care interventions in reducing time to TB diagnosis and prevalence of undiagnosed TB and HIV in primary care in Blantyre, Malawi. Participants (≥ 18 years) attending a primary care clinic with TB symptoms (cough of any duration) will be randomly allocated to one of three groups: (i) standard of care; (ii) optimised HIV diagnosis and linkage; or (iii) optimised HIV and TB diagnosis and linkage. We will test two hypotheses: firstly, whether prompt linkage to HIV care should be prioritised for adults with TB symptoms; and secondly, whether an optimised TB triage testing algorithm comprised of digital chest x-ray evaluated by computer-aided diagnosis software and sputum GeneXpert MTB/Rif can outperform clinician-directed TB screening. The primary trial outcome will be time to TB treatment initiation by day 56, and secondary outcomes will include prevalence of undiagnosed TB and HIV, mortality, quality of life, and cost-effectiveness. Conclusions: The PROSPECT Study will provide urgently-needed evidence under “real-life” conditions to inform clinicians and policy makers on how best to improve TB/HIV diagnosis and treatment in Africa. Clinical trial registration: NCT03519425 (08/05/2018)