Indian Scientists Identify Better Drug Treatment For Severe Scrub Typhus

A team of Indian scientists has identified a significantly more effective treatment for severe scrub typhus a life threatening bacterial infection that kills thousands of people every year. The study, published in the New England Journal of Medicine (NEJM), shows that treating patients with a combination of intravenous antibiotics doxycycline and azithromycin is more effective than the current monotherapy of using either drug alone. Using data from the  Intravenous Treatment for Scrub Typhus (INTREST) clinical trial, researchers from several Indian institutes compared the efficacy and safety of three 7-day intravenous antibiotic treatments (doxycycline, azithromycin, or a combination of both) in patients with severe scrub typhus.

They 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 7. The poor outcome, defined as a composite of death, persistent complications, or prolonged fever was reduced by nearly one-third, to 33 percent for combination therapy versus 47 percent for doxycycline and 48 percent for azithromycin, according to the researchers. INTREST is the largest ever randomized controlled trial on the treatment of scrub typhus, and the only one on the treatment of severe scrub typhus."Combination therapy with intravenous doxycycline and azithromycin is a better, more effective way to treat severe scrub typhus than monotherapies of either drug by itself," said INTREST study lead author Professor George M Varghese, from Christian Medical College (CMC) in Vellore, Tamil Nadu.

"This new evidence will change treatment guidelines, leading to swifter recovery and potentially saving thousands of lives of people with scrub typhus in the future," Varghese said in a statement. A life-threatening infection caused by the bacteria Orientia tsutsugamushi, scrub typhus is transmitted to humans by bites from tiny infected mites. Scrub typhus is a major public health threat in India, other South Asian countries, and around the tropics and kills an estimated 10 percent of the approximately one million people infected by it every year. Scrub typhus typically presents as a fever that may be associated with headaches, coughs, shortness of breath, and brain symptoms, like confusion and disorientation. One-third of patients develop a severe disease that affects multiple organs in the body and leads to lethally low blood pressure.

Death rates in severe diseases can reach up to 70 percent without treatment and 24 percent with treatment. Researchers do not know for certain why a combination of doxycycline and azithromycin should be more clinically effective in the treatment of severe scrub typhus than either of the drugs alone. The study found that when both azithromycin and doxycycline were administered together to patients with severe scrub typhus, the bacteria were cleared away quickly and patients improved faster. This could be because doxycycline and azithromycin stop the bacteria from producing proteins through different, but complementary, mechanisms, the researchers said.

As a consequence the combination of the two drugs may have reduced bacterial growth and multiplication, leading to quicker control of bacterial growth and more rapid resolution of symptoms, they said. The team at CMC Vellore collaborated with researchers at Mahidol Oxford Tropical Medicine Research Unit, Thailand, and Wellcome Trust Thailand Asia and Africa Programme for the study. PGI Chandigarh, IGMC Shimla, PGIMS Rohtak, JIPMER Pondicherry, CMC Vellore, SVIMS Tirupati, and KMC Manipal were the seven participating centers across India.