Tag Archive for: Douglas Postels

sick boy with malaria

New guidance to optimize blood sugar monitoring in cerebral malaria

A Children’s National Hospital research team based in Malawi pinpointed the optimal duration and frequency for monitoring the blood glucose in children with cerebral malaria, providing a roadmap to improve the treatment and outcomes for young patients diagnosed with the life-threatening disease.

Published in the American Journal of Tropical Medicine and Hygiene, the findings analyzed data from 1,674 pediatric cases to recommend the best schedule for periodic bedside point-of-care laboratory testing in children with cerebral malaria (CM). Currently, World Health Organization (WHO) guidelines state that blood glucose should be monitored in all forms of severe malaria, but they do not include advice on the timing or duration of the measurements.

Children’s National neurologist Douglas Postels, M.D., M.S., led a team of trainees from Howard University, The George Washington University, the University of Washington and Children’s National to collect and analyze patient data that led to the creation of evidence-based recommendations for glucose monitoring.

“If blood glucose in children with severe malaria is too low, the child is at high risk of death,” Dr. Postels said. “What we found in this research study is both interesting and important, and we hope our study results will help the WHO in creating evidence-based guidelines for blood glucose monitoring in children with cerebral malaria.”

The big picture

In 2021, 247 million people contracted malaria worldwide, killing some 619,000 primarily in Africa. Almost 80% were children under 5 years old, making it one of the most virulent pediatric diseases in the world. Many who survive experience significant neurologic, cognitive and behavioral morbidities.

Dr. Postels works at Queen Elizabeth Central Hospital in Blantyre, Malawi, caring for patients on the Pediatric Research Ward and conducting research aimed at improving outcomes. The clinical team works without access to many medical tools that are considered standard throughout more advanced economies. Yet this team has one of the lowest mortality rates for cerebral malaria across Africa, thanks to their ongoing research to better understand the pathophysiology of malaria and improve its treatment.

The challenges are immense: During COVID-19, they battled supply chain issues that frustrated repairs on an aging MRI scanner. After the second tropical cyclone struck in the last two years, Blantyre was left without power for a week and without water for a month.

“You can imagine trying to run a hospital with no water,” Dr. Postels said. “During Cyclone Freddy, it was raining like crazy, and people were collecting water in bins—anything they could collect it in — to use for handwashing, as well as trying to clean instruments and supplies.”

What they’re saying

Using evidence-based guidelines to optimize care becomes important in sub-Saharan Africa, where resources are scarce. Running laboratory-based blood studies frequently is an inefficient use of supplies and laboratory reagents. Results of point-of-care testing are also available more rapidly and at less cost than studies performed in hospital labs.

An accompanying editorial in the journal said the new research on glucose monitoring in cerebral malaria “provides valuable data that could help clinicians in resource-limited settings improve CM management with more efficient use of available resources.” The work is increasing calls for further study and updates to international guidelines.

The bottom line

According to the team’s analysis, blood glucose should be measured in children with CM on admission and every six hours for the first 24 hours. If all results in the first 24 hours are normal, clinicians can stop testing.  If any blood sugar levels in the first 24 hours are low, the patient’s blood glucose should be checked for another 24 hours.

“This testing strategy captures 100% of the children who have a glucose level of 2.2 mmol/L or less, the definition of hypoglycemia in severe malaria,” Dr. Postels said.  “We want to do enough, but not too much.”

The overarching goal for Dr. Postels and the trainees who join him in Blantyre is improving care.  “If we can help clinicians better care for children with cerebral malaria, then hopefully we can make a small contribution to decreasing the death rate and improve neurologic outcomes of the children who survive,” he said. “That’s my hope.”

3d illustration of blood cells, plasmodium causing malaria disease

International projects spearheaded by Children’s National Neurology leaders

NIH approves grant for clinical trial on pediatric cerebral malaria in Malawi

3d illustration of blood cells, plasmodium causing malaria disease

Cerebral malaria, when patients lapse into coma after developing a malaria infection, is the most severe neurological complication of infection with Plasmodium falciparum.

The National Institutes of Health (NIH) approved a $5.8 million grant for a Phase I/IIa randomized clinical trial of 6-diazo-5-oxo-L-norleucine (DON), a new medication for pediatric cerebral malaria. Douglas Postels, M.D., neurologist at Children’s National Hospital, will serve as the trial’s principal investigator. The clinical trial will enroll participants in Blantyre, Malawi.

More than 400,000 people die each year from malaria. Cerebral malaria, when patients lapse into coma after developing a malaria infection, is the most severe neurological complication of infection with Plasmodium falciparum. Many children who survive are left suffering from neurological complications because of the disease, leaving some unable to walk, see or go to school. Dr. Postels and others are seeking to initiate this clinical trial with the primary goal to save lives and improve the quality of life for children who survive the disease.

“The purpose of this study is to see if DON is safe in the Malawian population,” Dr. Postels said, noting that adult participants will be enrolled in the first year and children subsequently. “Once the medication has proven to be safe, our intention is to expand this research elsewhere in Africa allowing us to enroll more children and evaluate whether DON decreases the likelihood of death or neurological disability in pediatric cerebral malaria.”

DON was originally tested 50 years ago as an anti-cancer agent but was recently repurposed by the National Institute of Allergy and Infectious Diseases (NIAID) for pediatric cerebral malaria. The current clinical trial is a collaborative project with the NIAID scientists who performed the pre-clinical testing with DON.

“There are currently no adjunctive treatments, used in combination with intravenous anti-malarial medications, that decrease death or disability in pediatric cerebral malaria,” Dr. Postels said. “Our hope is that DON will be the “magic bullet” that helps these critically ill children.”

Improving access to epilepsy care in Ethiopia

Over the next three years, Tesfaye Zelleke, M.D., neurophysiologist at Children’s National Hospital, the Comprehensive Pediatric Epilepsy Program team and the Children’s National Global Health Initiative will create a sustainable program to reduce the epilepsy treatment gap in Ethiopia in collaboration with the Ethiopian Ministry of Health.

In a three-tier approach, the program is looking to help children in the country benefit from the increased access to the treatment and care for epilepsy, the most common neurologic disorder affecting about 1% of the population.

Ethiopia is one of the poorest countries in Africa with very limited access to epilepsy care — there are a handful of pediatric neurologists for a population of over 120 million. Only few referral hospitals have neurology clinics and those clinics are largely concentrated in Addis Ababa, the capital city. Improving access to epilepsy care in resource poor countries like Ethiopia would require utilizing non-neurologist providers, a task-shifting model.

“In the first year, we will focus on creating an epilepsy center of excellence, training of trainers (local non-neurologist providers), create treatment guidelines for epilepsy, and produce health education material for families and public,” said Dr. Zelleke. “In the subsequent years, we plan to expand to other areas outside of Addis Ababa — the Ethiopian capital — and collaborate with epilepsy advocacy groups to continue to increase access to care.”

After the three years, Dr. Zelleke and the team have envisioned working closely with the country’s Ministry of Health to further the impact of the project at a national level.