Elsevier

The Lancet

Volume 348, Issue 9020, 13 July 1996, Pages 86-89
The Lancet

Articles
Scrub typhus infections poorly responsive to antibiotics in northern Thailand

https://doi.org/10.1016/S0140-6736(96)02501-9Get rights and content

Summary

Background

Rickettsia tsutsugamushi, the aetiological agent of scrub typhus, is common in Asia and readily infects visitors to areas where disease transmission occurs. Rapid defervescence after antibiotic treatment is so characteristic that it is used as a diagnostic test for R tsutsugamushi infection. Reports from local physicians that patients with scrub typhus in Chiangrai, northern Thailand responded badly to appropriate antibiotic therapy prompted us to do a prospective clinical evaluation and antibiotic susceptibility testing of human rickettsial isolates.

Methods

The clinical response to doxycycline treatment in patients with early, mild scrub typhus in northern Thailand was compared with the results of treatment in Mae Sod, western Thailand. Prototype and naturally occurring strains of R tsutsugamushi were tested for susceptibility to chloramphenicol and doxycycline in mice and in cell culture.

Findings

By the third day of treatment, fever had cleared in all seven patients from Mae Sod, but in only five of the 12 (40%) from Chiangrai (p<0·01). Median fever clearance time in Chiangrai (80 h; range 15–190) was significantly longer than in Mae Sod (30 h; range 4–58; p<0·005). Conjunctival suffusion resolved significantly more slowly in Chiangrai (p<005). Antibiotics prevented death in mice infected by Chiangrai strains of R tsutsugamushi less often than after infection by the prototype strain (p<0·05). Only one of three Chiangrai strains tested in cell culture was fully susceptible to doxycycline.

Interpretation

Chloramphenicol-resistant and doxycycline-resistant strains of R tsutsugamushi occur in Chiangrai, Thailand. This is the first evidence of naturally occurring antimicrobial resistance in the genus Rickettsia.

Introduction

Scrub typhus is an acute, febrile disease, common in rural Asia. The causative organism, Rickettsia tsutsugamushi, is transmitted to humans by bites of larval mites known commonly as chiggers. An eschar and regional lymphadenopathy often develop at the site of inoculation, and may be followed by a systemic infection ranging in severity from symptomless to fatal. Visitors to enzootic areas readily become infected.1 During World War II, 18 000 cases of scrub typhus occurred in allied military personnel;2 1255 persons became ill with R tsutsugamushi infection on two small islands off the coast of New Guinea during a four-month period.3 Response to treatment with doxycycline or chloramphenicol is generally rapid and life-saving;4 antimicrobials have reduced scrub typhus case-fatality ratios that reached 50% during the pre-antibiotic era5 to zero when treatment was started promptly.4 R tsutsugamushi infection is generally so responsive to treatment that if fever has not abated within 48 h, the diagnosis is considered unlikely.6

Reports from local physicians that patients with scrub typhus in Chiangrai, northern Thailand responded poorly to appropriate antibiotic treatment prompted us to do a prospective clinical evaluation and antibiotic susceptibiity testing of human rickettsial isolates.

Section snippets

Patients

Clinical studies were conducted at two tertiary-care hospitals in Thailand; Chiangrai Prachanuchroa Hospital in the north and Mae Sod Hospital in the west. R tsutsugamushi antibody titres were determined by the highly specific indirect immunoperoxidase (IIP) test in feverish patients with clinical manifestations typical of scrub typhus.7 Patients were included in the study if the IgM titre on admission was 1:400 or greater and/or the IgG titre was 1:1600 or greater. Previous studies at these

Hospital studies

There were 12 patients from Chiangrai and seven from Mae Sod with mild scrub typhus who presented during the first week of illness. All survived and were discharged when they had remained febrile (⩽37·2°C) for at least 24 h before hospital discharge. None vomited their medication. All had previously been well, were HIV seronegative, and had no sign or symptom atypical of scrub typhus nor evidence of a second illness. There were no significant differences in admission characteristics between the

Discussion

Patients with scrub typhus usually become afebrile within 24–36 h after beginning antibiotics. After a single oral dose of 200 mg of doxycycline, 90% of Malaysian patients were afebrile within 48h.14 The average duration of fever after the start of treatment of 60 US servicemen who acquired scrub typhus during the Vietnam war was 27·8 h for tetracycline and 34·7 h for chloramphenicol.15 90% of all patients were free from fever within 48 h.15 In another series of patients in Vietnam, fever

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