The Impact of Antimicrobial Stewardship in Children in Low- and Middle-income Countries A Systematic Review

BackgroundAntimicrobial stewardship (AMS) is central to the World Health Organisation Global Action Plan against antimicrobial resistance (AMR). If antibiotics are used without restraint, morbidity and mortality from AMR will continue to increase. In resource-rich settings, AMS can safely reduce antibiotic consumption. However, for children in low- and middle-income countries (LMIC), the impact of different AMS interventions is unknown.AimTo determine the impact of different AMS interventions on antibiotic use and clinical and microbiologic outcomes in children in LMIC.MethodsMEDLINE, Embase and PubMed were searched for studies of AMS interventions in pediatric population in LMIC settings. Controlled trials, controlled before-and-after studies and interrupted time series studies were included. Outcomes assessed were antibiotic use, multidrug-resistant organism (MDRO) rates, clinical outcomes and cost.ResultsOf 1462 studies, 34 met inclusion criteria including a total population of >5,000,000 in 17 countries. Twenty were in inpatients, 2 in ED, 10 in OPD and 2 in both. Seven studies were randomized controlled trials. All types of interventions reported a positive impact on antibiotic prescribing. AMS bundles with education, and clinical decision tools appeared more effective than guidelines alone. AMS interventions resulted in significantly decreased clinical infections (4/4 studies) and clinical failure (2/2) and reduced MDRO colonization rate (4/4). There was no concomitant increase in mortality (4/4 studies) or length of stay (2/2).ConclusionMultiple effective strategies exist to reduce antibiotic consumption in LMIC. However, marked heterogeneity limit conclusions regarding the most effective approach, particularly regarding clinical outcomes. Overall, AMS strategies are important tools in the reduction of MDRO-related morbidity in children in LMIC

Neonatal BCG vaccination reduces interferon gamma responsiveness to heterologous pathogens in infants from a randomised controlled trial

Background Bacille Calmette-Guérin (BCG) vaccination has beneficial non-specific (heterologous) effects that protect against non-mycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial seven months after randomisation. Methods A whole blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands. Results Compared to BCG-naïve infants, BCG-vaccinated infants had increased production of MIG and IFN-γ in response to mycobacterial stimulation and decreased production of IFN-γ in response to heterologous stimulation. Reduced IFN-γ responses to heterologous stimulants and TLR ligands were attributable to a decrease in the proportion of infants who mounted a detectable IFN-γ response. BCG-vaccinated infants also had increased production of MIG and IL-8, and decreased production of IL-10, MIP-1α and MIP-1ß, the pattern of which varied by stimulant. IL-1Ra responses following TLR1/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination. Conclusions BCG vaccination leads to changes in IFN-γ responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation varies by pathogen

Emerging resistance to empiric antimicrobial regimens for pediatric bloodstream infections in Malawi (1998-2017)

Background The adequacy of the WHO Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi. Methods We determined the change in population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998-2017). AMR profiles were assessed by the disc diffusion method and trends over time were evaluated. Results A total 89,643 pediatric blood cultures were performed, and 10,621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ≤5 years of age fell from a peak of 11.4 per 1,000 persons in 2002 to 3.4 per 1,000 persons in 2017. Over two decades, resistance of Gram-negative pathogens to all empiric first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ≤5 years increased from 3.4% to 30.2% (p<0.001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (p<0.001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (p<0.001). Conclusions The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens resistant to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly expanding AMR in childhood BSI

Implementation of a novel ultrasound training programme for midwives in Malawi:A mixed methods evaluation using the RE-AIM framework

IntroductionDespite recommendation that all women receive an ultrasound in pregnancy prior to 24 weeks', this remains unavailable to many women in low-income countries where trained practitioners are scarce. Although many programmes have demonstrated efficacy, few have achieved longterm sustainability, with a lack of information about how best to implement such programmes. This mixed-methods study aimed to evaluate the implementation of a novel education package to teach ultrasound-naive midwives in Malawi basic obstetric ultrasound, assessing its impact in the context of the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework.MethodsThe study ran across six sites in Malawi between October 2020 and June 2021, encompassing three phases; pre-implementation, implementation and post-implementation. Twenty nine midwives underwent a bespoke education package with matched pre and post course surveys assessed their knowledge, attitudes and confidence and "hands on" assessments evaluating practical skills. Training evaluation forms and in-depth interviews explored their satisfaction with the package, with repeat assessment and remote image review evaluating maintenance of skills.Results28/29 midwives completed the training, with significant increases in knowledge, confidence and practical skills. Adherence to the education package varied, however many changes to the proposed methodology were adaptive and appeared to facilitate the efficacy of the programme. Unfortunately, despite reporting approval regarding the training itself, satisfaction regarding supervision and follow up was mixed, reflecting the difficulties encountered with providing ongoing in-person and remote support.ConclusionThis programme was successful in improving trainees' knowledge, confidence and skill in performing basic obstetric ultrasound, largely on account of an adaptive approach to implementation. The maintenance of ongoing support was challenging, reflected by trainee dissatisfaction. By evaluating the success of this education package based on its implementation and not just its efficacy, we have generated new insights into the barriers to sustainable upscale, specifically those surrounding maintenance

Midwife‐Led Ultrasound Scanning to Date Pregnancy in Malawi: Development of a Novel Training Program

The use of ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organization. However, this modality remains unavailable to many women in low-income countries where trained practitioners are scarce. Although previous initiatives have demonstrated efficacy in training midwives and technicians to perform antenatal ultrasound, these programs have often been too long and too complex to be realistic within the specific constraints of this context, highlighting the need for a novel and pragmatic approach. We describe the development and piloting of a bespoke course to teach midwives 3 fundamental components of early antenatal ultrasound scanning: (1) to identify the number of fetuses, (2) to confirm fetal viability, and (3) to determine gestational age. Having established that 5 days is insufficient, we propose that the minimum duration required to train ultrasound-naive midwives to competency is 10 days. Our completed program therefore consists of one and one-half days of didactic teaching, followed by 8 and one-half days of supervised hands-on practical training in which trainees are assessed on their skills. This package has subsequently been successfully implemented across 6 sites in Malawi, where 28 midwives have achieved competency. By describing the processes involved in our cross-continental collaboration, we explain how unexpected challenges helped shape and improve our program, demonstrating the value of preimplementation piloting and a pragmatic and adaptive approach

Training in Ultrasound to Determine Gestational Age (TUDA): Evaluation of a Novel Education Package to Teach Ultrasound-Naive Midwives Basic Obstetric Ultrasound in Malawi

IntroductionAlthough ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organisation, it remains unavailable to many women in low-income countries where trained practitioners are scarce. This study aimed to evaluate a novel, context-specific education package to teach midwives basic obstetric ultrasound, including the determination of gestational age by measurement of fetal femur length.MethodsThe study was conducted across six sites in Malawi in January 2021. Following a virtual “training of the trainers”, local teams delivered a 10-day programme encompassing both didactic and “hands on” components. Matched pre and post course tests assessed participants' knowledge of key concepts, with Objective Structured Clinical Examinations used to evaluate practical skills. To achieve a pass, trainees were required to establish the gestational age to within ±7 days of an experienced practitioner and achieve an overall score of &amp;gt;65% on five consecutive occasions. A matched pre and post course survey explored participants' attitudes and confidence in performing ultrasound examinations.ResultsOf the 29 midwives who participated, 28 finished the programme and met the criteria specified to pass. 22 midwives completed the matched knowledge tests, with the mean (SD) score increasing from 10.2 (3.3) to 18 (2.5) after training (P &amp;lt;0.0001). Mean difference 7.9, 95% CI 6.5–9.2. Midwives passed 87% of the Observed Structured Clinical Examinations, establishing the gestational age to within ±7 days of an experienced practitioner in 89% of assessments. Beliefs regarding the importance of antenatal ultrasound increased post course (p = 0.02), as did confidence in performing ultrasound examinations (p &amp;lt;0.0001).ConclusionThis study demonstrates not only that ultrasound-naive practitioners can be taught to perform basic obstetric ultrasound dating scans, confidently and competently, after 10 days of training, but also that local teams can be orientated to successfully deliver the programme virtually. Previous ultrasound training initiatives, while often more comprehensive in their syllabus, have been of considerably longer duration and this is likely to be a barrier to upscaling opportunities. We propose that this focused training increases the potential for widescale and sustainable implementation.</jats:sec

Lessons learnt from the rapid implementation of reusable personal protective equipment for COVID-19 in Malawi

The SARS-CoV-2 pandemic has challenged health systems and healthcare workers worldwide. Access to personal protective equipment (PPE) is essential to mitigate the risk of excess mortality in healthcare providers. In Malawi, the cost of PPE represents an additional drain on available resources. In the event of repeated waves of disease over several years, the development of sustainable systems of PPE is essential. We describe the development, early implementation and rapid scale up of a reusable gown service at a tertiary-level hospital in Blantyre, Malawi. Challenges included healthcare worker perceptions around the potential of reduced efficacy of cotton gowns, the need to plan for surge capacity and the need for ongoing training of laundry staff in safety and hygiene procedures. Benefits of the system included increased coverage, decreased cost and reduced waste disposal. The implementation of a reusable cotton gown service is feasible, acceptable and cost-effective in tertiary centres providing specialist COVID-19 care at the height of the pandemic. This innovation could be expanded beyond low-income settings

Implementation of a novel ultrasound training programme for midwives in Malawi: A mixed methods evaluation using the RE-AIM framework

INTRODUCTION: Despite recommendation that all women receive an ultrasound in pregnancy prior to 24 weeks', this remains unavailable to many women in low-income countries where trained practitioners are scarce. Although many programmes have demonstrated efficacy, few have achieved longterm sustainability, with a lack of information about how best to implement such programmes. This mixed-methods study aimed to evaluate the implementation of a novel education package to teach ultrasound-naive midwives in Malawi basic obstetric ultrasound, assessing its impact in the context of the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. METHODS: The study ran across six sites in Malawi between October 2020 and June 2021, encompassing three phases; pre-implementation, implementation and post-implementation. Twenty nine midwives underwent a bespoke education package with matched pre and post course surveys assessed their knowledge, attitudes and confidence and "hands on" assessments evaluating practical skills. Training evaluation forms and in-depth interviews explored their satisfaction with the package, with repeat assessment and remote image review evaluating maintenance of skills. RESULTS: 28/29 midwives completed the training, with significant increases in knowledge, confidence and practical skills. Adherence to the education package varied, however many changes to the proposed methodology were adaptive and appeared to facilitate the efficacy of the programme. Unfortunately, despite reporting approval regarding the training itself, satisfaction regarding supervision and follow up was mixed, reflecting the difficulties encountered with providing ongoing in-person and remote support. CONCLUSION: This programme was successful in improving trainees' knowledge, confidence and skill in performing basic obstetric ultrasound, largely on account of an adaptive approach to implementation. The maintenance of ongoing support was challenging, reflected by trainee dissatisfaction. By evaluating the success of this education package based on its implementation and not just its efficacy, we have generated new insights into the barriers to sustainable upscale, specifically those surrounding maintenance

Interventions to reduce preterm birth and stillbirth, and improve outcomes for babies born preterm in low- and middle-income countries: A systematic review

BACKGROUND: Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required. METHODS: A systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted. RESULTS: 179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions. CONCLUSIONS: Evidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts