Working Groups Research Areas Believed to be Critical For Reducing Childhood Mortality.
The CHAIN Network is led by a core group of individuals that have, over the years, fostered and built solid foundations. With vision and perseverance, The CHAIN Network has recruited, one by one, accomplished researchers, doctors, nurses, as well as coordinators and other skilled staff to work together as teams with a common goal. The CHAIN Network leaders have extensive experience in running clinical trials in difficult settings and have been embedded within the communities they serve for years. The CHAIN Network will grow from these solid foundations.
Social & Behavioral Science
Acute illness and undernutrition in children usually occur against a background of social and economic disadvantage. It is conceivable that no amount of nutritional or anti-infective interventions will be effective in preventing longer term post-discharge mortality if key social constraints exist. CHAIN’s social science working group aims to understand the contribution of modifiable social factors to mortality and to other poor outcomes of acutely ill children, both in hospital and in the post-discharge period. In addition, the Network seeks to understand the true societal and financial costs associated with poor nutrition and acute illness.
Nutrition & Metabolism
‘Undernutrition’ encompasses a range of macro- and micronutrient deficiencies that usually co-exist. For children with acute illness, metabolic disturbances affect nutrient metabolism, energy production and cellular homeostasis, while enteropathy impacts nutrient absorption and growth recovery. Evidence suggests that glycogen depletion reduces tolerance to physiological insults, such as hypoxia, while interfering with basic cellular membrane function. These nutritional and metabolic deficits are potential reasons why malnourished children fail to cope with infection and are mechanisms that may cause death without preceding warning signs. The Nutrition and Metabolism working group seeks to identify a definable metabolic phenotype that leads to inpatient death and that may be amenable to novel intervention.
Causes of Death
The causes of death among malnourished children are hard to elucidate and not well understood. The gold standard in establishing cause of death is to conduct post mortem studies but these are limited by social and cultural barriers. This working group focuses on the design of ethically and culturally appropriate tools to help improve acceptance of autopsy or of targeted tissue sampling in order to better understand the causes of death among children with acute illness and malnutrition.
Respiratory Disease & Tuberculosis
Many clinicians suspect that undiagnosed tuberculosis (TB) may be responsible for many cases of acute illness and malnutrition. However, TB is notoriously difficult to diagnose in children. A significant proportion of inpatient and post-discharge mortality may be due to either occult undiagnosed TB or to incident TB that occurs in the setting of continued vulnerability and susceptibility. If TB is an important factor in acute illness among undernourished children, they may benefit from empiric tuberculosis treatment. The Respiratory Disease and TB Working Group aims to utilize the cohort follow up to determine the frequency of undiagnosed TB among malnourished children suffering from acute illnesses.
Immunity & Infection
Children with malnutrition are at increased risk of life-threatening infection, even after therapeutic feeding. However, the nature of immunological dysfunction is unclear and only a small proportion of children with a sepsis-like clinical presentation have positive bacterial cultures. Using the CHAIN platform, this group will examine clinical data and tissue samples for evidence of invasive infection and impaired immune function associated with malnutrition. This work will lead to a better understanding of the sepsis-like presentment that appears to cause death in many acutely unwell malnourished children. The group also aims to determine the consequences of antimicrobial resistance (AMR) in pathogens causing invasive infections and in bacteria carried in the gut. The hospital environment and the antibiotics given may influence the susceptibility of pathogens causing disease after discharge and hence outcomes of those infections.
Enteric function & Infection
The enteric system is critical for the maintenance of normal immune function, and nutrient absorption. Alterations in the biology of the gut caused by pathogens or medical intervention may be associated with poor recovery from acute illness. The CHAIN Network’s Enterics group aims to understand the role of intestinal pathogens, enteropathy and gut microbiome in causing death and growth failure in acutely ill children in order to then target these with treatment interventions.
Undernutrition in Infancy
Malnourished infants experience very high mortality and incidence of severe infections such as pneumonia and diarrhoea. However, nutritional rehabilitation guidelines for infants under 6 months are currently based on minimal evidence. This working group will describe the patterns and consequences of breastfeeding practices among children that are acutely unwell. In addition, they will determine how inpatient re-lactation and other breast-feeding support prevents further deterioration in child health.
James A Berkley 'Jay'
Malnutrition can impair the neuro-cognitive development of a child which can lead to extended disabilities and impact their survival. In low resource settings, little is known about the prevalence of neurodevelopmental disability and its impact on childhood survival. Therefore, The CHAIN Cohort will screen children with and without malnutrition to assess the burden and extent of disabilities. Validated, developmental screening tools and questionnaires will be used and children will be followed longitudinally to assess progression and impact on mortality.