Researchers identify better drug treatment for severe scrub typhus

This new study, the largest ever randomised controlled trial on the treatment of severe scrub typhus, was published in The New England Journal of Medicine

A combination of antibiotic drugs is more effective in treating severe scrub typhus, a major public health threat in India and other south Asian nations, than single-drug therapies, a research by an Indian multi-institute team has found.

Severe scrub typhus, which primarily affects rodents and is transmitted to humans (zoonoses) by the larvae of trombiculid mites, is a life-threatening infection caused by the bacteria, Orientia tsutsugamushi, which affects a million people a year and claims over 1.5 lakh lives.

The research team led by Prof George M Varghese from the prestigious Christian Medical College (CMC), Vellore and the INTREST trial investigators found that a ‘combination antibiotic treatment’ (using a combination of drugs) is more effective for treating severe scrub typhus than single-drug therapies.

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The team 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 treatment with intravenous doxycycline and azithromycin 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. Seven institutes from the country, including CMC, KMC, Manipal, PGIMER, Chandigarh, and JIPMER, Puducherry, collaborate in the study.

Prof Varghese, Department of Infectious Diseases, CMC, said the study found that 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, meningoencephalitis, and kidney failure when using a combination of azithromycin and doxycycline to treat.

“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,” he added.

In the current study, about 800 adult patients with severe scrub typhus were included and 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 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. The combination of the two drugs may have result in a more complete blockade of protein synthesis and consequently reduced bacterial growth and multiplication.

Prof Varghese said 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,” he said.