by Evangelyn Nkwopara, Senior Research Manager and Clinical Trials Specialist at Save the Children US
It is 7:30AM in a small district hospital in Lilongwe, Malawi, and the pediatric triage unit is packed full of anxious parents seeking care for their sick infants or children. Here a dedicated team of research nurses and clinicians, part of the Innovative Treatments in Pneumonia (ITIP) project, work their way through the crowd looking for possible signs of pneumonia in hopes of catching the illness at its earliest stages in order to answer critical questions about this disease. No infectious disease kills more children under the age of five than pneumonia, and the symptoms tend to mimic other childhood illnesses making pneumonia hard to detect and treat. Amoxicillin is recommended as an effective first-line treatment, and in resource-limited settings such as Malawi, the World Health Organization’s (WHO) Integrated Management of Childhood Illness (IMCI) guidelines are used to diagnose pneumonia by identifying fast breathing and/or chest indrawing in a child with cough or difficulty breathing. However, the WHO IMCI guidelines for pneumonia have low specificity, particularly in regards to fast breathing pneumonia, leading to possible misclassification and ultimately, inappropriate treatment. There are a number of conditions, as well as factors, other than pneumonia that may cause fast breathing in a child. Which fast breathing cases are true pneumonia? Are antibiotics necessary for treatment of fast breathing?
In Lilongwe, Malawi, Save the Children Federation, in collaboration with partners at the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, University of Malawi College of Medicine, and the University of Washington, have been investigating these questions along with others in hopes of determining the best treatment options for childhood pneumonia. The primary goals of the ITIP project are to provide evidence assessing 1) whether treatment with amoxicillin dispersible tablets is necessary for fast breathing childhood pneumonia, and 2) the optimal duration of treatment with amoxicillin dispersible tablets for chest indrawing childhood pneumonia in a malaria-endemic setting in Africa. Collecting African-specific data may contribute to updates to the current IMCI guidelines that are informed by the local context. Comprised of two clinical trials and one prospective observational study, the ITIP project began in 2016 enrolling children two to 59 months of age with community-acquired pneumonia at Bwaila District and Kamuzu Central Hospitals in Lilongwe, Malawi.
Two years later, the results of the fast breathing pneumonia clinical trial, ITIP1, have now been published in the November 2018 issue of the Journal of the American Medical Association, Pediatrics. Enrolled HIV-uninfected children diagnosed with fast breathing pneumonia were randomized to receive either placebo or amoxicillin dispersible tablet treatment for three days. The findings from this trial indicate that despite the low specificity of fast breathing as a sign of pneumonia, treatment with amoxicillin for children diagnosed with fast breathing might be warranted in this setting. Out of the 1126 children enrolled to the trial, 7% of children in the placebo group failed treatment by Day 4 compared to 4% among those who received amoxicillin. Of note, however, fast breathing pneumonia resolved by Day 4 in 93% of children without antibiotics. These results shed some light on how to address fast breathing childhood pneumonia in a region such as Malawi; yet, more research is needed to define and better understand which children benefit most from antibiotic treatment.
Work continues in the ITIP project with enrollment ongoing in ITIP2, the chest indrawing pneumonia trial, as well as analysis of the data from the observational study, ITIP3. It is through research such as the ITIP project that Malawi and other countries in Africa will gain critical information needed to put into place evidence-based policies and treatment guidelines that will significantly reduce the number of children whose lives are cut short by pneumonia.
Photos submitted by Evangelyn Nkwopara, Save the Children US
Evangelyn Nkwopara, MS, is a senior research manager and clinical trials specialist in the Technology Accelerator unit at Save the Children US, and is part of the protocol and study operations team for the Innovative Treatments in Pneumonia (ITIP) project in Lilongwe, Malawi.