Severe cases of the mite borne scrub typhus disease may be better treated by a combination of antibiotics rather than single-drug therapies, according to a study by a team of Indian researchers.
Severe Scrub Typhus caused by the bacteria Orientia tsutsugamushi leads to a life-threatening infection, which primarily affects rodents, and is transmitted to humans (zoonoses) by the larvae of trombiculid mites.
The disease 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 the patients infected with scrub typhus could die inspite of diagnosis and treatment.
One-third of the 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.
The team of researchers including from Christian Medical College in Vellore, Tamil Nadu, and PGIMER Chandigarh in a study of 800 adult patients demonstrated that treatment with intravenous doxycycline and azithromycin is more effective than using either drug on its own.
The findings, published in The New England Journal of Medicine, showed that antibiotic combo therapy led to an early discharge of patients -- by day seven -- from hospital. The patients also had fewer persisting complications, such as respiratory distress syndrome (ARDS), hepatitis, hypotension/shock, meningoencephalitis, and kidney failure. The overall mortality rate in this study was 12 per cent.
"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," Prof George M Varghese, from CMC's Department of Infectious Diseases, said in a statement.
Scrub typhus is a major public health threat in India and other South Asian countries. It is estimated that in endemic regions, about a billion people are at risk of contracting the infection, while a million people get infected and 1.5 lakh people die from it every year.
As Orientia tsutsugamushi is a bacterium which multiplies and survives inside host cells, it is important that the antibiotic reaches high concentrations within host cells as well.
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 resolution of symptoms might have quickened, the researchers said.