Monthly Archives: February 2010

Cooling reduces death and disability in newborns deprived of oxygen at birth

Therapeutic hypothermia reduces risk of death and disability in infants with hypoxic-ischaemic encephalopathy, according to a new study by David Edwards and colleagues published in the British Medical Journal.

Hypoxic-ischaemic encephalopathy (damage to cells in the brain and spinal cord because of lack of oxygen) is a major cause of death and disability worldwide but there currently is no specific treatment available for it. Therapeutic hypothermia (cooling the body below the normal temperature of 37oC) has been reviewed previously and tested in several clinical trials for newborns with hypoxic-ischemic encephalopathy but the results have so far been inconclusive and consensus in the medical profession has not been reached.

Edwards and colleagues carried out a meta-analysis which took advantage of new studies, including results from the TOBY trial, and recently available additional data from previously reported studies to determine whether moderate hypothermia after hypoxic-ischemia encephalopathy in newborns improves survival and neurological outcome 18 months later.

The researchers analysed data from 1320 infants in 10 different randomised controlled trials (studies which reported at least mortality data). They also assessed data from a subset of three trials which had similar entry requirements—evidence of oxygen deprivation of birth and moderate and severe encephalopathy— which investigated neurological outcomes up to 18 months of age in 767 infants.

The investigators found that therapeutic hypothermia significantly reduced the combined death and severe disability rates in the subset of three trials with outcome data at 18 months. Cooling newborns deprived of oxygen at birth not only increased survival with normal neurological function but also reduced the rates of severe disability, cerebral palsy, severe neuromotor delay, severe neurodevelopmental delay and blindness. They observed no association between the severity of encephalopathy and the effect of cooling treatment. In their analysis of all the 10 different trials, the researchers showed that hypothermia therapy significantly reduced mortality.

“In the absence of any specific intervention to improve the dismal prognosis of infants with hypoxic-ischaemic encephalopathy, clinical enthusiasm for a novel treatment is understandable,” write the investigators, “this new meta-analysis … provides the highest level evidence that moderate hypothermia is efficacious in infants with hypoxic-ischaemic encephalopathy”. More work is needed to follow up the infants enrolled in these therapeutic hypothermia studies to determine whether they continue to reap the benefits of cooling therapy in later childhood.

ResearchBlogging.orgEdwards, A., Brocklehurst, P., Gunn, A., Halliday, H., Juszczak, E., Levene, M., Strohm, B., Thoresen, M., Whitelaw, A., & Azzopardi, D. (2010). Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data BMJ, 340 (feb09 3) DOI: 10.1136/bmj.c363

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African trypanosomes just love social networking

The procyclic form of african trypanosomes move together as a group when grown on a semisolid surface, according to new research from US scientists published in the journal PLoS Pathogens. This “social motility” is mediated by their flagellum and is a surprising new feature in trypanosome biology.

The African trypanosome, Trypansoma brucei, is a parasite which causes the disease “sleeping sickness” or African trypanosomiasis. The disease is endemic in regions of Sub-Saharan Africa and causes significant mortality, with estimates suggesting that 50,000-70,000 people are currently infected. The disease is transmitted to humans by bites from tsetse flies which are infected with the parasite. Initially, symptoms include fever and joint pains but once the parasite has entered the brain from the bloodstream it causes the neurological symptoms of the infection which gives the disease its name­—confusion, fatigue and sleep cycle disturbances. Under certain conditions, bacteria can move by various forms of social motility including gliding, swarming and twitching. They are known to group together in multicellular communities in which the bacteria can communicate together to move and respond to external stimuli. Trypansomes on the otherhand are thought to live as single cell entities.

Michael Oberholzer and colleagues studied the growth of procyclic T. brucei on a semisolid agar surface. The researchers found that the parasites grouped into a large multicellular community that could move across the surface of the agar, and could recruit more cells into the heaving mass (see the supporting video S1). They found that the parasite groups moved in a polarised direction and sent out “scout” parasites which moved in and out of the main group to come into contact with neighbouring cells. These scouts then communicated in some way to the main parasite crowd in order to merge new parasites into the main group or avoid them altogether by changing the direction of movement of the group. The investigators then used knockdown parasites which lacked a normal flagellum (a sort of tail on the parasite which helps them to move) and showed that their co-operative movements were mediated by their flagellum.

This research shows an interesting new facet to trypanosome biology and offers an insight into how the parasites behave. It will be interesting to see whether the trypanosomes act in the same way when they have infected humans or tsetse flies, and more research is needed to determine the physiological role of this trypanosome social motility.

ResearchBlogging.orgMichael Oberholzer, Miguel A. Lopez, Bryce T. McLelland, & Kent L. Hill (2010). Social motility in African Trypanosomes PLoS Pathogens, 6 (1) : doi:10.1371/journal.ppat.1000739

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