Neurological

Scientists are fixing the 100-year-old thriller of cerebral malaria utilizing neuroimaging strategies

Research shows that the leading cause of malaria deaths in adults is caused by lack of oxygen

Scientists have shown for the first time in a new study published in Clinical Infectious Diseases that cerebral malaria causes death in adults by causing a lack of oxygen in the brain.

Treatments that are already available, such as hypothermia, can slow the lack of oxygen in the brain in people with cerebral malaria. The researchers say these approaches to improving neural survival could soon be tried in adults with cerebral malaria alongside existing malaria treatments, hopefully to improve survival.

In 2019 there were an estimated 229 million cases of malaria worldwide. The estimated number of malaria deaths in 2019 was 409,000. Cerebral malaria is a serious, life-threatening complication of Plasmodium falciparum infection, the most widespread and deadliest of the five malaria parasites that can infect humans from the bite of Anopheles mosquitoes. Up to 20% of people with cerebral malaria die despite treatment for malaria, and neurocognitive after-effects are common in survivors.

The research team at the London School of Hygiene and Tropical Medicine (LSHTM), Ispat General Hospital at Heidelberg University and the Center for the Study of Complex Malaria in India used state-of-the-art MRI scanning techniques to monitor the brains of the malaria patients. The Center for the Study of Complex Malaria in India is one of the international centers of excellence for malaria research funded by the US National Institutes of Health.

By comparing the changes in the brains of survivors with those who died from the disease in different age groups, it was found that death in adults was often associated with severe oxygen starvation or hypoxia.

In children, however, the study confirmed previous research in Africa that severe brain swelling that led to respiratory failure was the leading cause of death in this age group.

The effects of malaria on the brain – the body’s most inaccessible organ – have puzzled scientists for the past century. But now, the advent of neuroimaging facilities in malaria-endemic areas is revolutionizing our understanding and enabling us to see what is going on in patients’ brains.

Co-Head of the Study and Associate Professor of Malaria Pathogenesis at LSHTM, Dr. Sam Wassmer

65 patients with cerebral malaria and 26 control patients with “uncomplicated” malaria who were treated at the Ispat General Hospital in Rourkela, India, took part in the study. They were given a type of MRI scan that can accurately measure changes in brain volume, an indicator of swelling and the diffusion of water molecules in tissues, an indicator of lack of oxygen.

The team found that brain swelling tends to decrease with age and that, unlike children, there is no correlation between brain swelling and death in adult patients from the same cohort.

Instead, fatal cases in adults were found to be severely oxygen deprived, affecting all brain structures, compared to only local anoxia in survivors. This was confirmed by significantly increased levels of specific molecules in the blood, which also indicate a lack of oxygen. These could be used to identify patients at risk of developing a fatal disease on admission and to inform their clinical management.

For years, scientists have relied on autopsies to understand the pathology of cerebral malaria, but these do not allow you to compare between survivors and deaths. Using neuroimaging techniques, we were able to see a snapshot of the living brain and identify the specific cause of death in adults.

Dr. Wassmer

The results suggest the tempting prospect of targeted treatments for cerebral malaria, and we are now planning clinical trials to test whether adjunct therapies for oxygen starvation are effective in adults. If successful, it could be a major step in reducing the death toll of one of the world’s deadliest diseases.

Dr. Sanjib Mohanty, Co-Leader of the Study at the Center for the Study of Complex Malaria in India

The authors acknowledge limitations in their work, including the fact that the study included only a relatively small number of fatal cases: 4 out of 38 adults and 3 out of 27 children with cerebral malaria. All participating patients were from the region of the Ispat General Hospital in Rourkela, India.

This project was funded in whole or in part by federal funding from the National Institute for Allergies and Infectious Diseases, the US National Institutes of Health, the Department of Health and Human Services under grants U19AI089676 and R21AI142472.

Read press release

publication

Sahu, PK, Hoffmann, A., Majhi, M., Pattnaik, R. Patterson, C., Mahanta, KC, Mohanty, AK, Mohanty, RR, Joshi, S. Mohanty, A., Bage, J., Maharana S., Seitz, A., Bendszus, M., Sullivan, SA, Turnbull, IW, Dondorp, AM, Gupta, H., Pirpamer, L., Mohanty, S. and Wassmer, SC Disease courses in cerebral malaria in children and Adult. Clinical Infectious Diseases. DOI: 10.1093 / cid / ciaa1647

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