tetracycline and Scrub-Typhus

Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.. To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.. We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.. Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).. For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.. We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.. Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chloramphenicol; Doxycycline; Humans; Macrolides; Randomized Controlled Trials as Topic; Rifampin; Scrub Typhus; Tetracycline

Topics: Adult; Chlamydia Infections; Drug Resistance, Multiple, Bacterial; Humans; Male; Mycoplasma Infections; Scrub Typhus; Tetracycline

To assess the clinical efficacy of short-course doxycycline in the treatment of scrub typhus, we compared conventional 7-day tetracycline therapy with 3-day doxycycline therapy in 116 patients. Patients were randomized to receive either tetracycline (500 mg four times daily; n = 50) or doxycycline (100 mg twice daily; n = 66) and were followed for 4 weeks after the completion of treatment. The cure rate was 100% in the tetracycline group and 93.9% in the doxycycline group (P > .05). The two groups did not differ significantly in terms of the interval required for defervescence or for the alleviation of symptoms. There were no relapses in either group. These data suggest that 3-day doxycycline therapy is as effective as conventional 7-day tetracycline therapy for the cure of scrub typhus and the prevention of relapses.

Topics: Adult; Aged; Aged, 80 and over; Doxycycline; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Recurrence; Scrub Typhus; Tetracycline

The use of doxycycline, as a prophylactic antibiotic against scrub typhus was investigated in a prospective, randomized, double-blind study. Twenty volunteers were divided into two similar groups. Beginning three days before exposure to Leptotrombidium fletcheri chiggers infected with Rickettsia tsutsugamushi, and continuing for six weeks after exposure, one group received weekly 200-mg oral doses of doxycycline and the other group received a placebo. Nine of 10 doxycycline-treated subjects remained well during prophylaxis but developed antibody to scrub typhus, whereas nine of 10 subjects given the placebo required treatment for scrub typhus. Therefore, the efficacy of the regimen in preventing scrub typhus was 89% (eight cases prevented of nine expected). Ten days after successfully completing prophylaxis, eight of nine subjects reported minor self-limiting symptoms. A single dose of doxycycline was given on day 3 of illness to volunteers who developed scrub typhus. Such therapy was initially effective but was frequently followed by relapse and cannot be recommended.

Topics: Adult; Antibodies, Bacterial; Double-Blind Method; Doxycycline; Drug Evaluation; Humans; Male; Middle Aged; Orientia tsutsugamushi; Prospective Studies; Recurrence; Scrub Typhus; Tetracycline; Trombiculidae

A single dose of 200 mg of doxycycline was shown to be as effective as a seven day course of tetracycline, in patients suspected of having scrub typhus. 65 (44%) of the 149 patients studied fulfilled the criteria for definite diagnosis of scrub typhus; 10 had an additional diagnosis. Rickettsia tsutsugamushi was isolated from 49 (75%) patients. There was no difference between the two treatment groups in time to defervescence, abolition of cough and headache, or in the time taken to recover well-being. There were no relapses in either group. Of the remaining 84 patients, a causal diagnosis was achieved in 52. Irrespective of a diagnosis there was no difference in apparent response to either doxycycline or tetracycline.

Topics: Adolescent; Adult; Aged; Doxycycline; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Scrub Typhus; Tetracycline

Topics: Albuminuria; Anemia; Arrhythmias, Cardiac; Aspartate Aminotransferases; Chloramphenicol; Conjunctivitis; Evaluation Studies as Topic; Fever; Hepatomegaly; Humans; Hypotension, Orthostatic; Leukopenia; Lymphatic Diseases; Male; Military Medicine; Recurrence; Scrub Typhus; Skin Ulcer; Splenomegaly; Tetracycline

Scrub typhus is caused by Orientia tsutsugamushi and has a near global prevalence. It is associated with local and systemic manifestations that lead to morbidity and mortality. Given the nonspecific presentation of fever in a returning traveler, a high index of suspicion and thorough skin examination for eschar are critical to establishing a diagnosis. Early treatment is crucial to avoid severe outcomes, further highlighting the need to include scrub typhus in differential diagnosis. An accompanying narrative case explores the epidemiology, diagnosis, and management of scrub typhus.

Topics: Anti-Bacterial Agents; Female; Humans; Male; Orientia tsutsugamushi; Scrub Typhus; Tetracycline; Tropical Climate

Scrub typhus is an important febrile disease in Southeast Asia and is caused by Orientia tsutsugamushi. Fluoroquinolones have proved to be effective for scrub typhus in an animal model. However, it is unclear whether they are also effective clinically.. We retrospectively reviewed the hospital-based medical records of patients diagnosed to have scrub typhus by an indirect immunofluorescence antibody assay or PCR at a large referral hospital in Taiwan for a 6-year period (2001-2007). To determine the efficacy of levofloxacin for the treatment of scrub typhus, we divided the patients into a levofloxacin-treated group and a tetracycline antibiotics-treated group.. Out of 132 patients with scrub typhus, 71 initially received levofloxacin and 61 initially received tetracycline antibiotics. There was no statistically significant difference in the effective rate between the two groups (91.5% and 95.1% cured, respectively; p=0.648). The time to defervescence in the levofloxacin-treated group was longer than in the other group (49+/-41.1 and 24+/-19.6hours, respectively; p=0.001). In the patients with higher APACHE II scores, higher mortality was found in the levofloxacin-treated group (44.4% and 0%; p=0.033).. Levofloxacin is effective in patients with scrub typhus, but has a longer time to defervescence compared with tetracycline antibiotics. When levofloxacin is used for severe scrub typhus, higher mortality may be attributed to the longer time to defervescence.

Topics: Anti-Bacterial Agents; Female; Humans; Levofloxacin; Male; Middle Aged; Ofloxacin; Retrospective Studies; Scrub Typhus; Taiwan; Tetracycline; Treatment Outcome

Patients with tsutsugamushi disease sometimes die if they do not receive appropriate chemotherapy. This study measured the concentration of several cytokines both before and after the administration of tetracyclines, and evaluated the changes in cytokine levels in patient serum to investigate the relationship between serum levels of cytokines and disease severity.. A total of nine patients were infected with Orientia tsutsugamushi. The diagnosis of tsutsugamushi disease was made using an indirect immunoperoxidase antibody test. The serum concentrations of cytokines were measured using enzyme-linked immunosorbent assays.. The levels of interleukin (IL)-10 (mean 71.7 pg/ml) and IL-12p40 (mean 588 pg/ml) were elevated in all patients in the acute phase, above the normal upper limits. Tumor necrosis factor-alpha (TNF-alpha) levels (mean 9.20 pg/ml) were elevated in 89% and interferon-gamma (IFN-gamma) levels (mean 41.0 pg/ml) in 44% of patients. The down-regulation of these overproduced cytokines was observed after chemotherapy. There was a significant correlation between the concentrations of TNF-alpha in the acute phase and the severity of disease (r=0.918).. The concentration of TNF-alpha may predict the severity of tsutsugamushi disease in the acute infectious phase.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-12 Subunit p40; Interleukin-4; Male; Middle Aged; Orientia tsutsugamushi; Scrub Typhus; Severity of Illness Index; Tetracycline; Tumor Necrosis Factor-alpha

Topics: Administration, Oral; Anti-Bacterial Agents; Antibodies, Bacterial; Diagnosis, Differential; DNA, Bacterial; Dose-Response Relationship, Drug; Fluorescent Antibody Technique; Hemoperitoneum; Humans; Male; Orientia tsutsugamushi; Polymerase Chain Reaction; Scrub Typhus; Tetracycline; Tomography, X-Ray Computed; Young Adult

A 65-year-old man was admitted because of high grade fever and cough after 3 days of gathering edible wild plants. Although ceftriaxone was given to him, his symptoms did not improve. His high grade fever escalated after changing the antibiotics (imipenem with erythromycin). His situation further declined with disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). As a result, he was transferred to the Department of Respiratory Medicine 7 days after admission. He was intubated and placed on mechanical ventilation and treated by polymyxin-direct hemoperfusion. The eschar on his chest wall caused us to suspect Tsutsugamushi disease and a blood test confirmed our suspicion. Since the antibodies for Tsutsugamushi were elevated we arrived at the diagnosis of Tsutsugamushi disease with DIC and ARDS. The administration of tetracycline was sufficient to significantly improve his condition. Because its complications are life threatening, when we see a patient with fever and eruptions, it is necessary to keep in mind the possibility of Tsutsugamushi disease. Careful anamnesis and physical examinations are most important for the diagnosis of Tsutsugamushi disease.

Topics: Aged; Anti-Bacterial Agents; Antibodies, Bacterial; Biomarkers; Disseminated Intravascular Coagulation; Hemoperfusion; Humans; Male; Orientia tsutsugamushi; Polymyxins; Respiratory Distress Syndrome; Scrub Typhus; Serologic Tests; Severity of Illness Index; Tetracycline; Treatment Outcome

A 35-year-old lady was admitted to hospital with fever and dry cough. Chest radiograph showed bilateral basal infiltrate. Her Weil-Felix test was strongly positive (OX-K > 1:160) and her fever came down with intravenous tetracycline. There was no improvement in the lung shadow and spirometry showed a severe restrictive defect. Open lung biopsy confirmed the diagnosis of interstitial pneumonitis. CT of thorax 6 months after presentation showed partial resolution of the interstitial shadow.

Topics: Adult; Biopsy; Female; Humans; Lung Diseases, Interstitial; Scrub Typhus; Spirometry; Tetracycline; Tomography, X-Ray Computed

Scrub typhus became a well recognized infectious disease threat to military operations in the Pacific Theater during World War II. Early diagnosis and treatment with tetracycline or chloramphenicol dramatically reduces the mortality and morbidity of this disease. Korea is a newly recognized scrub typhus endemic country. We report our experience with 189 scrub typhus patients seen at a civilian outpatient clinic in Chinhae, Republic of Korea, from 1985 through 1990, and verify the accuracy of clinical diagnosis by serologic tests.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Chloramphenicol; Humans; Korea; Middle Aged; Military Medicine; Mite Infestations; Scrub Typhus; Tetracycline; Time Factors; United States

Rickettsial infections are considered a major cause of illness among inmates of Thai-Kampuchean border displaced persons camps. In the absence of sophisticated laboratory support, it had become common practice to treat patients with obscure fevers with tetracycline as a 'diagnostic' test for typhus. This study evaluated a group of 67 randomly selected camp inmates who presented with fever and had findings that indicated a specific diagnosis. Differential blood counts, malaria smears, hemoglobin determinations, blood cultures, dengue and Japanese encephalitis virus and rickettsial IgM and IgG antibody titers were determined. Patients were then treated with tetracycline and followed. They could be divided into six groups after data were analyzed. Those with no final diagnosis comprised 14 cases (21%), 4 patients (6%) were found to have dengue fever, 6 (9%) scrub typhus and 39 (58%) had murine (endemic) typhus. None of the bacterial blood cultures drawn from this group grew any organisms and no tick typhus or Japanese encephalitis was diagnosed. Analysis of symptoms and signs did not allow clinical differentiation between groups. All patients became afebrile and well within 1-5 days of starting tetracycline therapy. We conclude that rickettsial disease is a major health problem in the Thai-Kampuchean border camps. The incidence of murine typhus increased during the dry season and was more prevalent among males. The use of tetracycline as a 'therapeutic test' did not distinguish between rickettsial, viral and undiagnosed febrile diseases.

Topics: Cambodia; Dengue; Female; Humans; Male; Prospective Studies; Refugees; Scrub Typhus; Tetracycline; Thailand; Typhus, Endemic Flea-Borne

Scrub typhus rarely figures among the imported tropical diseases in western Europe. Rickettsia tsutsugamushi is transmitted by larval mites. A typical eschar develops at the site of the mite bite during the incubation period, after which systemic symptoms (remittent or continuous high fever, severe headache, tender lymphatic glands and symptoms of bronchitis) develop with sudden onset. Antibodies appear during the second week and can be shown by a positive and increasing titer against Prot. OXK (Weil-Felix) or by specific rickettsial agglutination. The Weil-Felix reaction is neither very sensitive nor very specific. Therefore, treatment should be started as soon as suspicion arises whether a positive serology is available or not. Tetracycline drugs are effective treatment and fever subsides in less than 24 hours in most patients. - We report the rare observation of a tourist who imported tsutsugamushi fever from India.

Topics: Animals; Arachnid Vectors; Humans; Insect Bites and Stings; Male; Middle Aged; Mites; Scrub Typhus; Tetracycline

Topics: Administration, Oral; Adolescent; Adult; Cambodia; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Scrub Typhus; Tetracycline; Thailand

Athymic mice were taken ill and died from infection with the high virulence as well as the low virulence strains of Rickettsia tsutsugamushi, and they did not improve in spite of tetracycline therapy. Moreover, neither 7S nor IgM antibody was detected by immunofluorescent antibody method in serum samples of athymic mice infected with the high virulence strain. Although immune serum-transfer exhibited some protective effect in athymic mice infected with the high virulence strain, it was far lower than in euthymic mice. Although both athymic and euthymic mice having received non-immune T-lymphocytes were taken ill and died, the mice having received immune T-lymphocytes survived infection with the high virulence strain. This protective capacity of T-lymphocytes was weak by 10 days after immunization of donor mice, became firm after a month and lasted as long as 12 months without decay. For athymic mice infected with the low virulence strain, not only immune but also non-immune T-lymphocytes from euthymic mice exhibited significant protective effect. By treatment of immune T-lymphocytes with anti-Thy-1.2 or anti-Lyt-1.2 alloserum, the protective capacity was lost entirely, and considerably diminished by treatment with anti-Lyt-2.2 alloserum in a homologous system using the high virulence strain. The results show that the inhibition of progress of tsutsugamushi disease is principally dependent on cellular immune mechanism(s) and that the production of antibody against R. tsutsugamushi is thymus-dependent.

Topics: Animals; Antibodies, Bacterial; Immune Sera; Immunization; Immunoglobulin M; Mice; Mice, Inbred BALB C; Mice, Nude; Orientia tsutsugamushi; Scrub Typhus; T-Lymphocytes; Tetracycline

The influence of tsutsugamushi fever infection on the metabolism of blood lymphocytes of mice differing in susceptibility to Rickettsia tsutsugamushi and of rifampicine and tetracycline treatment was studied. In susceptible mice, the activity of oxidation-reduction processes in lymphocytes increased at 7--10 days of the disease and became normal upon recovery of the animals. In mice with low susceptibility this increase of the activity began and terminated much earlier, at 3--5 days. Treatment of the infection with antibiotics resulted in a rapid arrest of the disease and normalization of the lymphocyte activity. The relationship between susceptibility of the animals to R. tsutsugamushi and the activity of oxidation-reduction enzymes is discussed on the example of succinate dehydrogenase.

Topics: Animals; Antibodies, Bacterial; Disease Models, Animal; Lymphocytes; Mice; Orientia tsutsugamushi; Rifampin; Scrub Typhus; Succinate Dehydrogenase; Tetracycline

Between May and September 1973, 68 cases of scrub typhus in Chinese military personnel on the Pescadores Islands were studied. The common symptoms and signs were fever, chills, headache, eschar, myalgia, and lymph node enlargement. Most eschars were located in the axilla, waist, groin and genitals, and neck. These lesions were painless and not noticed by the patients themselves. Regional lymph node enlargement at the site of eschar drainage was common. Relative bradycardia with fever was observed in 40%, a skin rash in 35% of the patients. Leucopenia was noted more frequently in the febrile than in the convalescent stage, but more than half of the patients had a normal count. Lymphocytosis was prominent, especially during the convalescent period. An acceleration of ESR was noted. Instead of depression of the erythroid series in the marrow which was reported previously, 47% of examined patients were found to have erythroid hyperplasia. Two patients showed marked hypocellularity of the marrow in the acute febrile stage; later on became normocellular. Albuminuria was present in 15 and BUN increased in 12 patients. Elevation of serum bilirubin and SGOT was also noted. Biologic false positive VDRL tests were observed in nine patients. In 30 tests elevation of Proteus OX-K titres between 1:160 and 1:640 was noted. A geometric mean OX-K titre rise in the patients is presented; the mean titre reached a peak in the third week of illness, and then fell off. Most of the patients were treated with tetracycline 500 mg every six hours for about nine days. The fever usually subsided within 36 hours. Complications or mortality were not encountered.

Topics: Adult; Female; Humans; Male; Middle Aged; Military Medicine; Scrub Typhus; Taiwan; Tetracycline

Topics: Agglutination Tests; Chloramphenicol; Humans; Insect Bites and Stings; Male; Scrub Typhus; Tetracycline; Travel

Topics: Animals; Antibodies, Bacterial; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Infectious Mononucleosis; Male; Mice; Neurologic Manifestations; Orientia tsutsugamushi; Proteus; Scrub Typhus; Skin Manifestations; Skin Ulcer; Tetracycline; Time Factors; Vietnam

Topics: Chloramphenicol; Humans; Scrub Typhus; Tetracycline; Vietnam

Topics: Animals; Anti-Bacterial Agents; Chlamydia; Erythromycin; Fluorescent Antibody Technique; Male; Mice; Psittacosis; Rickettsia; Scrub Typhus; Streptomyces; Tetracycline; Time Factors

Topics: Adult; Afibrinogenemia; Humans; Male; Scrub Typhus; Tetracycline; Thrombophlebitis; Vietnam

Topics: Animals; Bacterial Vaccines; Humans; Methods; Mice; Orientia tsutsugamushi; Scrub Typhus; Tetracycline; Vaccination

Topics: Adult; Animals; Female; Humans; Male; Methacycline; Mice; Middle Aged; Scrub Typhus; Tetracycline

Topics: Chloramphenicol; Humans; Military Medicine; Scrub Typhus; Tetracycline

Topics: Anti-Bacterial Agents; Humans; Protein Synthesis Inhibitors; Scrub Typhus; Tetracycline