By Kate Pfizenmaier / Global WACh
Death from diarrheal disease is entirely preventable yet it remains the second leading cause of death worldwide in children under five. When a child arrives at a clinic with severe diarrhea in a low-income country, say Kenya, what dictates the treatment they get? How do we define the severity of their condition and when do we assume it could be life threatening?
The answer is more complex than you might think. Diarrhea doesn’t have just one cause - there are many- and the diagnostics to identify the different pathogens at the root of the problem are unreliable and rarely available in low-income countries. Symptoms, such as dehydration or dysentery, are used instead to guide treatment decisions. In a new study published in The Lancet Global Health, researchers from the University of Washington’s Department of Global Health found that many Shigella-infected children do not have dysentery when they arrive at the hospital and health systems may be missing a critical window for treating this potentially lethal bacteria.
Shigellosis - a bacterial infection characterized by loose and watery stool, dysentery, fever, and stomach cramps - is one of the leading causes of diarrheal deaths in children in low- and middle-income countries. International guidelines from the World Health Organization currently rely on patients to show signs of dysentery, or blood in their stool, before recommending treatment with antibiotics for diarrhea.
Dr. Kirk Tickell, University of Washington’s Department of Global Health and lead author of a recently published systematic review and meta-analysis on pediatric Shigella infection said, given the limitations of diagnostics and the danger of developing antibiotic resistance by over treating children without bacterial causes of diarrhea, “the pragmatic solution that people came up with 20 years ago was to assume that children who had Shigella would get dysentery, and to treat kids with dysentery with antibiotics. What we aimed to do is determine whether this logic still holds true, and we conclude that it does not.”
Researchers from the Global Center for the Integrated Health of Women, Adolescents, and Children (Global WACh) at the University of Washington, conducted a series of systematic reviews to determine whether dysentery appropriately identifies children most likely to benefit from antibiotic therapy and explored the efficacy of antibiotic therapy for treating both the symptom (dysentery) and the infection (Shigella). In their review, the authors found that Shigella-infection itself, not dysentery, is associated with mortality. Dr. Patricia Pavlinac, University of Washington’s Department of Global Health and senior author of the study emphasized “Our global goal is to prevent children from dying from diarrhea, so we must think critically about how to identify and intervene upon children with Shigella infections, before the infection leads to dysentery.”
The original guideline, encouraging antibiotics be given to children with dysentery, targeted a particular strain of Shigella, S.dysenteriae type 1. S.dysenteriae type 1 is more likely to cause dysentery than other Shigella species and was a major public health concern that caused pandemics of dysentery across Central America, South Asia, and Central and East Africa between 1968 and 1990. S. dysenteriae type 1, however, has shown global decline in recent studies while other species remained relatively constant. Changes in the dominant species of Shigella may be one reason why dysentery alone is no longer a reliable indicator for children with high-risk infection. Less S.dysenteriae type 1 may mean fewer children with Shigella getting dysentery and, therefore, fewer children receiving the potentially life-saving therapeutic of antibiotics.
Antibiotics are powerful tools for treating severe diarrhea, but rising concerns about antibiotic resistance and the potential to render these powerful tools ineffective or less effective in the future, have many in the diarrhea community concerned about overprescribing these medicines to treat the disease. Dr. Tickell says his team shares these concerns and that scientists and policy makers must “walk the fine line of using an incredibly powerful treatment today, but not creating problems tomorrow - it’s difficult.” In real-world settings, antibiotics are already widely prescribed to children with diarrhea. All antibiotics, however, are not created equal when it comes to treating Shigella and Tickell and Pavlinac are concerned that children may not be getting the right antibiotics. Currently, there is no guidance for clinicians on what antibiotic to use in treating non-dysenteric bacterial diarrhea.
So how do we determine when a child with diarrhea should get an antibiotic and when another treatment alone, such as oral rehydration salts (ORS) and zinc, will suffice? In their paper, Tickell and Pavlinac call for evidence-based approaches for managing Shigella cases where dysentery is not present and for continuing to aggressively manage dysentery to safe guard against future epidemics of S. dysenteriae type 1. One option for managing non-dysentery Shigella is to develop a rapid, inexpensive diagnostic tool to identify Shigella when children arrive at hospitals with diarrhea. In the absence of such a tool for low-resource settings, Pavlinac says her priority is “identifying which kids are at risk of dying from Shigella” and treating them with the best available tools. An approach broached by the authors is to consider a more holistic view of a child’s health and vulnerability by treating only children with known risk factors such as young age, malnutrition, and HIV infection when determining treatment for diarrhea rather than focusing on identifying the pathogen or associated symptom.
Their paper underscores the importance of continual re-assessment of international guidelines for pediatric illnesses like diarrhea. These critical assessments should be used to inform future research to address evidence gaps. Future directions might include moving towards a risk scoring tool that prioritizes antibiotic treatment for vulnerable children with diarrhea. “We’re not proposing more antibiotics, we’re proposing more data driven approaches to determine which child should receive an antibiotic” Dr. Pavlinac remarked. We have made substantial progress in reducing under 5 mortality, particularly those due to diarrheal disease. To continue progress to end diarrheal deaths we will need to identify and capture critically ill children slipping through the cracks in health systems around the world and, when necessary, consider altering our approach to their treatment.
Read the Lancet commentary on their findings by Karen L. Kotloff also published in The Lancet Global Health.
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