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Top abstracts from the second Paediatric and Child Health Association of Malawi Conference

Theme: Child is parent to the adult: survive, thrive and transform

The first Paediatric and Child Health Association of Malawi (PACHA) conference was in 2017. The inaugural event was held in Lilongwe, Malawi to bring together a multidisciplinary team of child health care professionals showcasing the best in locally conducted discovery and implementation research to address issues in daily practice and advance policy development in Malawi (1). The second biennial conference was held in Mangochi, Malawi from 17-19 October 2019 under the theme “Child is parent to the adult: survive, thrive and transform.” The conference team considered a diverse category of abstracts highlighting challenges to survival and well-being of children at different stages of growth and development and impact on their caregivers. With this holistic approach, the following top scoring abstracts were selected and are highlighted below.

Wongani Nyangulu 1 Elizabeth Glaser 2 Pui-Ying Iroh Tam 3,4,5

(PACHA Research Committee)

1.Public Health Nutrition Research Group – GSK Malaria Consultancy, College of Medicine, Malawi, 2. Heller School for Social Policy and Management, Brandeis University, Waltham, Massachusetts, U.S.A., 3. Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi, 4. Liverpool School of Tropical Medicine, U.K., 5. University of Malawi College of Medicine, Malawi

Childhood meningitis in Malawi in era of conjugate vaccines and increasing antimicrobial resistance, 2000-2018

Maryke Nielsen 1,2,3 Stephen Ray 1,2,3 Kondwani Kawaza 3 Brigitte Denis 4 Stephen Gordon 2,4 Michael J. Griffiths 1,2 Enitan Carrol 1,2 Neil French 1,2 Queen Dube 3 Pui-Ying Iroh Tam 2,3,4

1.Institute of Infection and Global Health, University of Liverpool, U.K., 2. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Malawi, 3. Queen Elizabeth Central Hospital, Malawi, 4. Liverpool School of Tropical Medicine, U.K.

Background: The burden of meningitis remains highest in resource limited settings with the highest rates of death and long-term disability amongst survivors in children ≤ 5 years of age. The aim of this study is to assess trends in cerebral-spinal fluid (CSF) cultures in children ≤ 5 years admitted to a large teaching hospital over 18 years in Blantyre, Malawi, a malaria endemic setting outside of the epidemic “meningitis belt”.

Methods: We determined the overall trends in CSF culture positive isolates between 2000 and 2018 divided into period 4 periods for analysis (2000-2004, 2005-2009, 2010-2014, 2015-2018) including changes in antimicrobial resistance (AMR) profiles.

Results: A total of 3,412 CSF samples were culture positive of which 2,260 were classified as pathogens and 1,152 as contaminants.  The total number of pathogenic isolates reached a nadir in 2012 but has since risen annually.  Significant reductions in CSF culture positive cases of Hemophilus influenzae (n=238, 25%, vs n=5, 1%) and Streptococcus pneumoniae (n=373, 39% vs n=38, 8%) are identified when comparing 2000-4 and 2015-2018. A notable increase in Klebsiella spp. (n=5, 0.5% vs n=76, 14%), E. coli (n=12, 1% vs n=49,10%) and Acinetobacter baumanii (n=0, 0% vs n=63, 13%) occurred during the same time periods.  The percentage of all pathogenic isolates resistant to ceftriaxone increased from 0% in period 1 to 64.8% in period 4. 

Conclusions: The total number of CNS infections in hospitalised children has decreased over the last 18 years, reflecting the comprehensive roll out of conjugate vaccines in Malawi. The increasing numbers of Gram-negative pathogens resistant to first-line antimicrobials is concerning. These data mirror the rapidly expanding AMR in childhood blood stream infections in our setting.

Determining the impact on mortality of treating low glycaemia in children admitted to Queen Elizabeth Central Hospital in Malawi (The sugar FACT trial)

Fatsani Ngwalangwa1 Chikondi H.A. Phiri 2 Queen Dube 2 Josephine Langton 1 Helena Hildenwall 3,4 Tim Baker1,2,3

1.Department of Paediatrics, University of Malawi, College of Medicine, Blantyre, Malawi,2. Queen Elizabeth Central Hospital, Blantyre, Malawi,3. Karolinska Institute,Global Health – Health System and Policy Research Group, Department of Public Health Sciences, Stockholm, Sweden, 4. Astrid Lindgren Children’s Hospital, Karolinska University Hospital Stockholm, Sweden

Background: Hypoglycaemia is a medical emergency affecting 7.3% of children admitted to hospital in low-income settings and with a reported case fatality rate of up to 42%. The World Health Organization (WHO) currently defines hypoglycaemia as a blood glucose level below 2.5 mmol /L in a well-nourished child and below 3.0 mmol/L in a malnourished child. However, this definition is not evidence-based, and several studies point at an increased mortality also among critically ill children with low-glycaemia, i.e. a blood glucose of 2.5-5.0 mmol/l. The management of hypoglycaemia involves prompt treatment with intravenous dextrose to raise blood sugar levels. Due to the lack of evidence on whether treatment with intravenous dextrose can improve outcomes in low glycaemic patients, this study was done to determine the impact on in-hospital mortality of raising the hypoglycaemia treatment cut-off level from 2.5 mmol/l to 5 mmol/l.

Methods: We conducted a pragmatic randomized controlled trial to determine the impact on in-hospital mortality of administering dextrose to severely ill children with low-glycaemia at arrival to the emergency department in two hospitals in Malawi between December 2016 and January 2019. All children with a WHO emergency sign aged one month to five years with low glycaemia were randomized to receive either the intervention; a 10% dextrose 5ml/kg bolus followed by a dextrose maintenance infusion or control; no dextrose treatment as per standard treatment guidelines. The primary outcome was in-hospital mortality and the secondary outcome was 24hr mortality. Analysis was conducted using logistic regression by intention-to-treat, with a secondary per-protocol analysis.

Results: A total of 332 participants were recruited into the study. Data for five participants was removed from the analysis. One hundred and sixty-eight patients (50.6%) were randomised into the intervention group. The mean ages in the intervention and control groups were 2.4 years (Range 0.9-4.9) and 2.3years (range 0.1-4.9) respectively. In-hospital mortality in the intervention group was 15.2% versus 16.1% in the control group with odds ratio 1.1 (95% CI 0.6-1.9). A total of 26 participants (8.0%) died within the first 24 hours of admission with 7.9% in the intervention compared to 8.0% in the control group with an odds ratio of 1.0 (95% CI 0.5-2.3)

Conclusion: The results suggest that early administration of dextrose does not improve outcomes among severely sick children who are admitted with low glycaemia. The increase in risk of mortality among this group of patients could be due to other factors like disease severity other than low blood glucose. There is a need to explore on the specific disease condition and mortality in low glycaemic patients.

Determinants of mortality in neonates with culture-negative sepsis in Queen’s neonatal unit

Lughano Ghambi1 Tessa de Baat1 Pui-Ying Iroh Tam1,2

1.Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi, 2. University of Malawi College of Medicine, Malawi

Background: Neonatal sepsis remains one of the leading causes of mortality in Malawi. Considering the nonspecific definition of neonatal sepsis, many babies with a presumed diagnosis are started on antibiotics, but many of those neonates treated for sepsis do not have culture-proven blood stream infection. This then leads to many babies being exposed unnecessarily to antibiotics which contributes to increasing rates of antimicrobial resistance. Therefore, describing features of neonates with culture-negative sepsis may help to minimize antibiotic exposure. Furthermore, identifying factors associated with mortality in neonates with culture-negative sepsis may assist the clinician when to initiate and discontinue antimicrobial therapy in those most at risk for poor outcomes. The aim of this study is to describe the characteristics of neonates with presumed sepsis and to determine the factors that are associated with death in neonates with culture-negative sepsis.

Methods: We conducted a prospective observational study which recruited all neonates that were treated for neonatal sepsis in Chatinkha nursery and had blood culture samples taken between November 2018 and February 2019. Data, including maternal factors, delivery factors, neonatal factors and outcomes were extracted and presented as proportions or median values. When comparing neonates with culture-negative sepsis that died to those that survived, simple univariate statistics were used.

Results: Between November 2018 and February 2019, 262 neonates had blood cultures obtained and data was completed for 258 neonates who were included in the analysis. Of the 258 neonates that had blood cultures, 225 were negative (87%) and 16 died (7%). Compared to neonates that survived, a higher proportion of those that died, had mothers who had <4 WHO-recommended antenatal visits (78% vs 64%), prenatal antibiotic exposure (33% vs 10%), were HIV-positive (20% vs 14%), delivered outside the hospital (25% vs 7%), and had prolonged rupture of membranes (25% vs 17%). A larger proportion of the neonates with culture-negative sepsis that died had, low birth weight (40% vs 4%), respiratory distress (25% vs 6%) and prematurity (31% vs 25%).

Conclusion: Though the sample size was small, our findings indicate that a larger proportion of neonates with culture-negative sepsis that die compared to those that survive, have mothers who had <4 antenatal visits, prenatal antibiotic exposure, were HIV-positive, delivered outside the hospital, had prolonged rupture of membranes, and the neonates had low birth weight, respiratory distress and prematurity. Therefore, factors other than sepsis are likely to contribute to their mortality and morbidity. In this setting clinicians should consider these when deciding to initiate and discontinue antimicrobials.

How should assent to research be sought in low income settings? Perspectives from parents and children in southern Malawi

Helen Mangochi1 Kate Gooding1,2 Aisleen Bennett1 Michael Parker3 Nicola Desmond1,2 Susan Bull3

1. Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi, 2. Liverpool School of Tropical Medicine, U.K., 3  Ethox Centre and Wellcome Centre for Ethics and Humanities, University of Oxford, U.K.

 

Introduction: Paediatric research in low-income countries is essential to tackle high childhood mortality. As with all research, informed consent is an essential part of ethical practice for paediatric studies. Ethics guidelines recommend that parents or another proxy provide legal consent for children to participate in research and children involvement in the decision making through providing assent. However, there remain uncertainties about when children are ready to give assent and the appropriate processes. Malawi does not yet have detailed guidelines on assent. Understanding community perspectives can assist in developing contextually appropriate assent guidance.

Methods: Qualitative research was conducted with children and parents in three contrasting settings in Southern Malawi (low-income urban, high-income urban and rural), to understand variations between socioeconomic and cultural contexts. Interviews were conducted with parents and their children who had participated in paediatric research to understand their experiences of assent and views on appropriate assent practice. Focus groups were also conducted, to understand broader social perspectives.

Results: We found widespread support for involving children in decisions on research participation. Participants identified a range of factors that affect children’s capacity to give assent, including physical maturity, intellectual capacity, emotional development, life experience and cultural norms. Age was often mentioned as a consideration but deemed an unreliable sole indicator of capacity to assent. In relation to appropriate assent processes, participants emphasized considerations such as supporting effective understanding and minimizing harms.

Conclusion: Participants agreed about the value of involving children in decisions on research, and the need to promote child’s decision-making capacity whilst respecting parents’ interest in child welfare. Developing practical guidance that meets these principals is challenging, particularly given the need of flexible approaches that suit different study types, children capacities and family environments. Further discussions within the Malawi research and ethics community will help develop contextually appropriate guidelines.

Reference

1.       Award-winning abstracts from the first Paediatric and Child Health Association of  Malawi Conference: Theme: Using a multidisciplinary team approach to improve child health outcomes throughout Malawi. Vol. 29, Malawi Medical Journal. 2017. p. 282–4.

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