Indian multi-institute researchers team identify better drug treatment for Severe Scrub Typhus, Health News, ET HealthWorld
Prof George M Varghese
, Infectious Diseases Physician and Researcher, Christian Medical College, Vellore and the INTREST trial investigators conducted a multi-centric, randomised controlled trial funded by the DBT/Wellcome India Alliance to identify the best treatment option for patients with severe scrub typhus. It demonstrated that intravenous doxycycline and azithromycin treatment is more effective than using either drug on its own.
This new study, the largest ever randomised controlled trial on the treatment of severe scrub typhus, was published recently in The New England Journal of Medicine.
The collaborating institutions included the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, Indira Gandhi Medical College & Hospital (IGMC) Shimla, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, Christian Medical College, Vellore, SVIMS Tirupati and KMC Manipal.
Explaining the significance of this research, Prof Varghese said, The implication of this study is that when using a combination of azithromycin and doxycycline to treat severe scrub typhus, more patients can be discharged from the hospital by day seven as they would have fewer persisting complications, such as respiratory distress syndrome (ARDS), hepatitis, hypotension/shock, meningoencephalitis, and kidney failure. This trial provides evidence that combination therapy with intravenous doxycycline and azithromycin is a better therapeutic option for the treatment of severe scrub typhus than monotherapies of either drug. This new evidence will change treatment guidelines and save the lives of thousands of people with scrub typhus in the future.
Highlighting the need for such research, Prof Varghese added, Scrub typhus typically presents as a fever that may be associated with headaches, coughs, shortness of breath, and brain symptoms, like confusion and disorientation. About six per cent of patients infected with scrub typhus could die in spite of diagnosis and treatment. One-third of patients develop severe disease that affects multiple organs in the body and leads to lethally low blood pressure. Death rates in severe disease can reach up to 70 per cent without treatment and 24 per cent with treatment.
Small trials conducted in Thailand and South Korea among patients with mild scrub typhus showed that both azithromycin and doxycycline have similar efficacy.
However, systematic reviews of available trials reveal that there is no uniformity in the doses of drugs used or in the outcomes of patients within the studies conducted so far. Hence, it was unclear which drug or how much should be used.
About 800 adult patients with severe scrub typhus were included in the current study. They were split in a 1:1:1 ratio into three groups through a randomisation process to receive intravenous doxycycline, intravenous azithromycin, or a combination of both intravenous doxycycline and azithromycin, respectively, for a duration of seven days. The treating team, study management group, and participants were not told which patient was assigned to which group or treatment regimen.
The study assessed the efficacy of treatment using death from any cause on day 28, persisting complications on day seven, and persisting fever on day five as indicators. The side effects of treatment were also assessed.
The trial found that combination therapy was superior to therapy with intravenous doxycycline or azithromycin alone. Patients who were treated with combination antibiotics had fewer complications from the infection on day seven. In line with other studies, this study also found that there was no difference in the outcome between using doxycycline or azithromycin alone. The overall mortality rate in this study was 12 per cent.
This study found that when both azithromycin and doxycycline were administered together to patients with severe scrub typhus, the bacteria were cleared away quicker and patients improved faster.
This could be because doxycycline and azithromycin stop the bacteria from producing proteins through different, but complementary, mechanisms. The combination of the two drugs may have resulted in a more complete blockade of protein synthesis and consequently reduced bacterial growth and multiplication. As combination therapy quickly controlled bacterial growth within the first week of infection, severe disease may have been prevented and the resolution of symptoms might have quickened.
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Thursday, March 2, 2023 at 1:42 pm