Continuous Glucose Monitoring in Resource-Constrained Settings for Hypoglycaemia Detection: Looking at the Problem from the Other Side of the Coin

The appearance, over a decade ago, of continuous glucose monitoring (CGM) devices has triggered a patient-centred revolution in the control and management of diabetes mellitus and other metabolic conditions, improving the patient’s glycaemic control and quality of life. Such devices, the use of which remains typically restricted to high-income countries on account of their elevated costs, at present show very limited implantation in resource-constrained settings, where many other urgent health priorities beyond diabetes prevention and management still need to be resolved. In this commentary, we argue that such devices could have an additional utility in low-income settings, whereby they could be selectively used among severely ill children admitted to hospital for closer monitoring of paediatric hypoglycaemia, a life-threatening condition often complicating severe cases of malaria, malnutrition, and other common paediatric conditions

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria.

BACKGROUND: Despite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention. METHODS: In this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem®) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations. RESULTS: Thirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters. CONCLUSIONS: Adjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria. The trial is registered with Clinicaltrials.gov, NCT02694874

Performance of lung ultrasound in the diagnosis of pediatric pneumonia in Mozambique and Pakistan

Introduction: Improved pneumonia diagnostics are needed in low-resource settings (LRS); lung ultrasound (LUS) is a promising diagnostic technology for pneumonia. The objective was to compare LUS versus chest radiograph (CXR), and among LUS interpreters, to compare expert versus limited training with respect to interrater reliability.Methods: We conducted a prospective, observational study among children with World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) chest-indrawing pneumonia at two district hospitals in Mozambique and Pakistan, and assessed LUS and CXR examinations. The primary endpoint was interrater reliability between LUS and CXR interpreters for pneumonia diagnosis among children with WHO IMCI chest-indrawing pneumonia.Results: Interrater reliability was excellent for expert LUS interpreters, but poor to moderate for expert CXR interpreters and onsite LUS interpreters with limited training.Conclusions: Among children with WHO IMCI chest-indrawing pneumonia, expert interpreters may achieve substantially higher interrater reliability for LUS compared to CXR, and LUS showed potential as a preferred reference standard. For point-of-care LUS to be successfully implemented for the diagnosis and management of pneumonia in LRS, the clinical environment and amount of appropriate user training will need to be understood and addressed

Serial lung ultrasounds in pediatric pneumonia in Mozambique and Pakistan.

Lung ultrasound (LUS) is a promising point-of-care imaging technology for diagnosing and managing pneumonia. We sought to explore serial LUS examinations in children with chest-indrawing pneumonia in resource-constrained settings and compare their clinical and LUS imaging courses longitudinally. We conducted a prospective, observational study among children aged 2 through 23 months with World Health Organization Integrated Management of Childhood Illness chest-indrawing pneumonia and among children without fast breathing, chest indrawing or fever (no pneumonia cohort) at 2 district hospitals in Mozambique and Pakistan. We assessed serial LUS at enrollment, 2, 6, and 14 days, and performed a secondary analysis of enrolled children's longitudinal clinical and imaging courses. By Day 14, the majority of children with chest-indrawing pneumonia and consolidation on enrollment LUS showed improvement on follow-up LUS (100% in Mozambique, 85.4% in Pakistan) and were clinically cured (100% in Mozambique, 78.0% in Pakistan). In our cohort of children with chest-indrawing pneumonia, LUS imaging often reflected the clinical course; however, it is unclear how serial LUS would inform the routine management of non-severe chest-indrawing pneumonia

Performance of lung ultrasound in the diagnosis of pediatric pneumonia in Mozambique and Pakistan.

INTRODUCTION: Improved pneumonia diagnostics are needed in low-resource settings (LRS); lung ultrasound (LUS) is a promising diagnostic technology for pneumonia. The objective was to compare LUS versus chest radiograph (CXR), and among LUS interpreters, to compare expert versus limited training with respect to interrater reliability. METHODS: We conducted a prospective, observational study among children with World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) chest-indrawing pneumonia at two district hospitals in Mozambique and Pakistan, and assessed LUS and CXR examinations. The primary endpoint was interrater reliability between LUS and CXR interpreters for pneumonia diagnosis among children with WHO IMCI chest-indrawing pneumonia. RESULTS: Interrater reliability was excellent for expert LUS interpreters, but poor to moderate for expert CXR interpreters and onsite LUS interpreters with limited training. CONCLUSIONS: Among children with WHO IMCI chest-indrawing pneumonia, expert interpreters may achieve substantially higher interrater reliability for LUS compared to CXR, and LUS showed potential as a preferred reference standard. For point-of-care LUS to be successfully implemented for the diagnosis and management of pneumonia in LRS, the clinical environment and amount of appropriate user training will need to be understood and addressed

Tracking SARS-CoV-2 introductions in Mozambique using pandemic-scale phylogenies: a retrospective observational study

9 hojas, 4 figuras, 1 tabla. Demographic data of the participants are available in the appendix (pp 40–42). Genome sequences are publicly available on GISAID. All scripts used for the analysis, and beta and delta subtree files are publicly available at https://gitlab.com/tbgenomicsunit/mozcovid. The study protocol (appendix pp 1–35) and clinical questionnaire (appendix pp 36–39) will be available with publicationBackground: From the start of the SARS-CoV-2 outbreak, global sequencing efforts have generated an unprecedented amount of genomic data. Nonetheless, unequal sampling between high-income and low-income countries hinders the implementation of genomic surveillance systems at the global and local level. Filling the knowledge gaps of genomic information and understanding pandemic dynamics in low-income countries is essential for public health decision making and to prepare for future pandemics. In this context, we aimed to discover the timing and origin of SARS-CoV-2 variant introductions in Mozambique, taking advantage of pandemic-scale phylogenies. Methods: We did a retrospective, observational study in southern Mozambique. Patients from Manhiça presenting with respiratory symptoms were recruited, and those enrolled in clinical trials were excluded. Data were included from three sources: (1) a prospective hospital-based surveillance study (MozCOVID), recruiting patients living in Manhiça, attending the Manhiça district hospital, and fulfilling the criteria of suspected COVID-19 case according to WHO; (2) symptomatic and asymptomatic individuals with SARS-CoV-2 infection recruited by the National Surveillance system; and (3) sequences from SARS-CoV-2-infected Mozambican cases deposited on the Global Initiative on Sharing Avian Influenza Data database. Positive samples amenable for sequencing were analysed. We used Ultrafast Sample placement on Existing tRees to understand the dynamics of beta and delta waves, using available genomic data. This tool can reconstruct a phylogeny with millions of sequences by efficient sample placement in a tree. We reconstructed a phylogeny (~7·6 million sequences) adding new and publicly available beta and delta sequences. Findings: A total of 5793 patients were recruited between Nov 1, 2020, and Aug 31, 2021. During this time, 133 328 COVID-19 cases were reported in Mozambique. 280 good quality new SARS-CoV-2 sequences were obtained after the inclusion criteria were applied and an additional 652 beta (B.1.351) and delta (B.1.617.2) public sequences were included from Mozambique. We evaluated 373 beta and 559 delta sequences. We identified 187 beta introductions (including 295 sequences), divided in 42 transmission groups and 145 unique introductions, mostly from South Africa, between August, 2020 and July, 2021. For delta, we identified 220 introductions (including 494 sequences), with 49 transmission groups and 171 unique introductions, mostly from the UK, India, and South Africa, between April and November, 2021. Interpretation: The timing and origin of introductions suggests that movement restrictions effectively avoided introductions from non-African countries, but not from surrounding countries. Our results raise questions about the imbalance between the consequences of restrictions and health benefits. This new understanding of pandemic dynamics in Mozambique can be used to inform public health interventions to control the spread of new variants. Funding: European and Developing Countries Clinical Trials, European Research Council, Bill & Melinda Gates Foundation, and Agència de Gestió d'Ajuts Universitaris i de Recerca.This publication was produced by MozCovid which is part of the EDCTP2 programme supported by the EU (grant number RIA2020EF-3005-MozCOVID). The COVID-19 testing was supported by Emory Global Health Institute, University of Emory, through the CHAMPS Program funded by the Bill & Melinda Gates Foundation (under the grant OPP1126780 to Robert Breiman, subcontract SC00003286). This work was also supported by the European Research Council under the EU’s Horizon 2020 Research and Innovation Program grant (101001038; TB-RECONNECT), the European Commission–NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global), the Departament d’Universitats i Recerca de la Generalitat de Catalunya (AGAUR; 2021 SGR 01517), and the Ministerio de Ciencia e Innovación (Spanish Government) Project PID2019–104477RB-I00. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya (http://cerca.cat/en/suma/). We also acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the Centro de Excelencia Severo Ochoa 2019–2023 Program (CEX2018–000806-S).Peer reviewe

Continuous Glucose Monitoring in Resource-Constrained Settings for Hypoglycaemia Detection: Looking at the Problem from the Other Side of the Coin

The appearance, over a decade ago, of continuous glucose monitoring (CGM) devices has triggered a patient-centred revolution in the control and management of diabetes mellitus and other metabolic conditions, improving the patient’s glycaemic control and quality of life. Such devices, the use of which remains typically restricted to high-income countries on account of their elevated costs, at present show very limited implantation in resource-constrained settings, where many other urgent health priorities beyond diabetes prevention and management still need to be resolved. In this commentary, we argue that such devices could have an additional utility in low-income settings, whereby they could be selectively used among severely ill children admitted to hospital for closer monitoring of paediatric hypoglycaemia, a life-threatening condition often complicating severe cases of malaria, malnutrition, and other common paediatric conditions

Paraplegia and spinal deformity in a Mozambican child with Pott's disease and tuberculous scrofula

A 4-year-old boy was admitted to our district hospital, in the southern region of Mozambique, with a 3-month history of night fevers, night sweats, a non-productive cough, weight loss, neck swelling, backache, and a progressive deformity of his back. 1 week earlier he had developed weakness of all limbs and was unable to walk

Paraplegia and spinal deformity in a Mozambican child with Pott's disease and tuberculous scrofula

A 4-year-old boy was admitted to our district hospital, in the southern region of Mozambique, with a 3-month history of night fevers, night sweats, a non-productive cough, weight loss, neck swelling, backache, and a progressive deformity of his back. 1 week earlier he had developed weakness of all limbs and was unable to walk

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

BACKGROUND: Despite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention. METHODS: In this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem(R)) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations. RESULTS: Thirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters. CONCLUSIONS: Adjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria. The trial is registered with Clinicaltrials.gov, NCT02694874