日本紅斑熱 1999～2019年 (IASR Vol. 41 p133-135: 2020年8月号).
Matsuyama H, Taira M, Suzuki M, Sando E.
Associations between Japanese spotted fever (JSF) cases and wildlife distribution on the Boso Peninsula, Central Japan (2006-2017).
J Vet Med Sci. 2020 Dec 5;82(11):1666-1670. doi: 10.1292/jvms.20-0377. Epub 2020 Oct 2.
Abstract/Text
Populations of large mammals have been dramatically increasing in Japan, resulting in damage to agriculture, forestry, and ecosystems. However, their effects on tick-borne diseases have been poorly studied. Here, we focused on the relationship between Japanese spotted fever (JSF), a tick-borne disease caused by Rickettsia japonica, and populations of large mammals. To explore factors that affected the area in which JSF cases occur, we used generalized linear mixed models (GLMMs). We demonstrated that the expansion of the area of JSF occurrence can be predicted by deer density and geographical factors, which is likely due to differences in landscape structure. However, the associated models have limitations because of the lack of information about the distribution of vectors and reservoirs. To reduce the risk of humans contracting JSF, potential reservoirs should be confirmed.
Sando E, Suzuki M, Katoh S, Fujita H, Taira M, Yaegashi M, Ariyoshi K.
Distinguishing Japanese Spotted Fever and Scrub Typhus, Central Japan, 2004- 2015.
Emerg Infect Dis. 2018 Sep;24(9):1633-1641. doi: 10.3201/eid2409.171436.
Abstract/Text
Japanese spotted fever (JSF) and scrub typhus (ST) are endemic to Japan and share similar clinical features. To document the clinical and epidemiologic characteristics that distinguish these 2 rickettsial diseases, during 2004-2015 we recruited 31 JSF patients, 188 ST patients, and 97 nonrickettsial disease patients from the southern Boso Peninsula of Japan. JSF occurred during April-October and ST during November-December. Patients with JSF and ST were significantly older and more likely to reside in wooded areas than were patients with nonrickettsial diseases. Spatial analyses revealed that JSF and ST clusters rarely overlapped. Clinical findings more frequently observed in JSF than in ST patients were purpura, palmar/plantar rash, hyponatremia, organ damage, and delayed defervescence after treatment. Although their clinical features are similar, JSF and ST differ in seasonality, geographic distribution, physical signs, and severity. Because a considerable percentage of patients did not notice rash and eschar, many rickettsial diseases might be underdiagnosed in Japan.
Sando E, Suzuki M, Katayama M, Taira M, Fujita H, Ariyoshi K.
Rickettsia japonica Infection after Land Leech Bite, Japan.
Emerg Infect Dis. 2019 Jun;25(6):1243-1245. doi: 10.3201/eid2506.181985.
Abstract/Text
We report a case of Rickettsia japonica infection in an 81-year-old man in central Japan. The patient had fever, rash, and an eschar but no evidence of a tick bite. His symptoms began 8 days after a land leech bite. The land leech is a potential vector of R. japonica.
Cunha BA, Baron J, Cunha CB.
Similarities and differences between doxycycline and minocycline: clinical and antimicrobial stewardship considerations.
Eur J Clin Microbiol Infect Dis. 2018 Jan;37(1):15-20. doi: 10.1007/s10096-017-3081-x. Epub 2017 Aug 17.
Abstract/Text
Doxycycline and, to a lesser extent, minocycline, have been used for decades to treat various serious systemic infections, but many physicians remain unfamiliar with their spectrum, interpretation of susceptibility results, pharmacokinetic/pharmacodynamic (PK/PD) properties, optimal dosing regimens, and their activity against MRSA, VRE, and multidrug-resistant (MDR) Gram-negative bacilli, e.g., Acinetobacter sp. This article reviews the optimal use of doxycycline and minocycline to treat a variety of infections and when minocycline is preferred instead of doxycycline.
Seki M, Ikari N, Yamamoto S, Yamagata Y, Kosai K, Yanagihara K, et al. Severe Japanese spotted fever successfully treated with fluoroquinolone. Internal medicine. 2006;45(22):1323-6. Epub 2006/12/16.
Mahara F, Miyamoto K, Fujita H, and Mutsuda T. Clinical Usefulness of Combination Therapy with Minocycline and Ciprofloxacin as a Treatment for Fulminant Cases of Japanese Spotted Fever. Clin Microbiol;Clinical Microbiology. 2014;3:176.
Itoh K, Kabata D, Shigemi H, Hirota T, Sakamaki I, Tsutani H, Mitsuke Y, Iwasaki H.
Evaluation of tetracycline and fluoroquinolone therapy against Japanese spotted fever: Analysis based on individual data from case reports and case series.
Int J Antimicrob Agents. 2023 Aug;62(2):106895. doi: 10.1016/j.ijantimicag.2023.106895. Epub 2023 Jun 18.
Abstract/Text
OBJECTIVES: Although approximately 40 years have passed since Japanese spotted fever (JSF) was first reported in Japan, its treatment has not yet been standardised. As in other rickettsial infections, tetracycline (TC) is the first-line treatment, but successful instances of fluoroquinolone (FQ) combination therapy in severe cases have been reported. However, the effectiveness of TC plus FQ combined treatment (TC+FQ) remains controversial. Therefore, the antipyretic effect of TC+FQ was evaluated in this study.
METHODS: A comprehensive search of published JSF case reports was conducted to extract individual patient data. In cases where it was possible to extract temperature data, after homogenising patient characteristics, time-dependent changes in fever type from the date of the first visit was evaluated for the TC and TC+FQ groups.
RESULTS: The primary search yielded 182 cases, with individual data evaluations resulting in a final analysis of 102 cases (84 in the TC group and 18 in the TC+FQ group) that included temperature data. The TC+FQ group had significantly lower body temperature compared with the TC group from Days 3 to 4.
CONCLUSIONS: Although TC monotherapy for JSF can eventually result in defervescence, the duration of fever is longer compared with other rickettsial infections such as scrub typhus. The results suggest that the antipyretic effect of TC+FQ was more effective, with a potential shortening of the duration that patients suffer from febrile symptoms.
Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.
Yasuda I, Sando E.
Combined treatment of Japanese spotted fever with tetracycline and fluoroquinolone requires careful evaluation using robust outcomes both in terms of its advantages and disadvantages.
Int J Antimicrob Agents. 2024 Aug;64(2):107201. doi: 10.1016/j.ijantimicag.2024.107201. Epub 2024 May 18.
Abstract/Text
Kutsuna S, Ohbe H, Matsui H, Yasunaga H.
Effectiveness of fluoroquinolone antimicrobials in addition to tetracyclines for Japanese spotted fever: A retrospective analysis using a national inpatient database.
Int J Infect Dis. 2022 Oct;123:70-75. doi: 10.1016/j.ijid.2022.08.006. Epub 2022 Aug 18.
Abstract/Text
OBJECTIVES: This study aim to evaluate the effectiveness of fluoroquinolone (FQ) antimicrobial therapy in combination with tetracyclines (TCs) in patients with Japanese spotted fever (JSF) using a nationwide inpatient database in Japan.
METHODS: We identified hospitalized patients diagnosed with JSF who were enrolled in the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2021. Patients who received FQ plus TC on the day of admission were compared with patients who received TC alone on the day of admission, using inverse probability of treatment weighting. The primary outcome was in-hospital mortality. Secondary outcomes were in-hospital complications, total hospitalization costs, and length of hospital stay.
RESULTS: We identified 1060 eligible patients. Of these, 434 (41%) received FQ plus TC on the day of admission and 626 (59%) received TC alone on the day of admission. Inverse probability of treatment weighting showed no statistically significant differences between the groups in in-hospital mortality, in-hospital complications, total hospitalization costs, and length of hospital stay.
CONCLUSION: This study did not show any significantly improved effectiveness using FQ antimicrobials in combination with TCs for treating JSF. Clinicians may need to be cautious in administering FQ and TC antimicrobials concomitantly in routine practice.
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Yasuda I, Toizumi M, Sando E.
Deleterious effects of a combination therapy using fluoroquinolones and tetracyclines for the treatment of Japanese spotted fever: a retrospective cohort study based on a Japanese hospital database.
J Antimicrob Chemother. 2024 Aug 1;79(8):1962-1968. doi: 10.1093/jac/dkae192.
Abstract/Text
OBJECTIVES: Tetracyclines are the standard treatment for rickettsiosis, including Japanese spotted fever (JSF), a tick-borne rickettsiosis caused by Rickettsia japonica. While some specialists in Japan advocate combining fluoroquinolones with tetracyclines for treating JSF, the negative aspects of combination therapy have not been thoroughly evaluated. Whether fluoroquinolones should be combined with tetracyclines for JSF treatment is controversial. The study aimed to evaluate the disadvantages of fluoroquinolones combined with tetracyclines for JSF treatment.
METHODS: This retrospective cohort study was conducted using a Japanese database comprising claims data from April 2008 to December 2020. The combination therapy group (tetracyclines and fluoroquinolones) was compared with the monotherapy group (tetracycline only) regarding mortality and the incidence of complications.
RESULTS: A total of 797 patients were enrolled: 525 received combination therapy, and 272 received monotherapy. The adjusted odds ratio (OR) for mortality was 2.30 [95% confidence interval (CI): 0.28-18.77] in the combination therapy group with respect to the monotherapy group. According to the subgroup analysis, patients undergoing combination therapy with ciprofloxacin experienced higher mortality rates compared with those receiving monotherapy (adjusted OR = 25.98, 95% CI = 1.71-393.75). Additionally, 27.7% of the combination therapy group received NSAIDs concurrently with fluoroquinolones. The combination therapy with NSAIDs group was significantly more likely to experience convulsions than the monotherapy without NSAIDs group (adjusted OR: 5.44, 95% CI: 1.13-26.30).
CONCLUSIONS: This study found no evidence that combination therapy improves mortality outcomes and instead uncovered its deleterious effects. These findings facilitate a fair assessment of combination therapy that includes consideration of its disadvantages.
© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.
Lee N, Ip M, Wong B, Lui G, Tsang OT, Lai JY, Choi KW, Lam R, Ng TK, Ho J, Chan YY, Cockram CS, Lai ST.
Risk factors associated with life-threatening rickettsial infections.
Am J Trop Med Hyg. 2008 Jun;78(6):973-8.
Abstract/Text
We retrospectively analyzed 92 cases of severe rickettsial infections in patients (median age = 49 years, 57% male, 37.0% with scrub typhus) in Hong Kong. Immunofluorescence assay was used for diagnostic confirmation. Identification of > or = 1 diagnostic sign (exposure history, rash, or eschar) was possible in 94.6% of the cases. Multivariate analysis suggested that pulmonary infiltrates (odds ratio [OR] = 25.2, 95% confidence interval [CI] = 3.9-160.9, P = 0.001) and leukocytosis (OR = 1.3, 95% CI = 1.0-1.5 per unit increase, P = 0.033) were independent predictors of admission to an intensive care unit (14.1%). Delayed administration of doxycycline was independently associated with major organ dysfunction (23.9%; oxygen desaturation, renal failure, severe jaundice, encephalopathy, cardiac failure) (OR = 1.2, 95% CI = 1.0-1.5 per day delay, P = 0.046; adjusted for age and rickettsia biogroup) and prolonged hospitalization > 10 days (25%) (OR = 1.4, 95% CI = 1.1-1.9 per day delay, P = 0.014). Treatment with fluoroquinolone/clarithromycin did not correlate with clinical outcomes (P > 0.05). Early empirical doxycycline therapy should be considered if clinico-epidemiologic signs of rickettsial infections are present.
Kutsuna S, Ohbe H, Matsui H, Yasunaga H.
Delayed Tetracycline Initiation Increases Mortality Risk in Patients With Japanese Spotted Fever: Retrospective Analysis Using a National Inpatient Database.
Open Forum Infect Dis. 2022 Nov;9(11):ofac573. doi: 10.1093/ofid/ofac573. Epub 2022 Oct 31.
Abstract/Text
BACKGROUND: This study aimed to determine the relationship between time to tetracycline therapy initiation and disease outcome in patients hospitalized with Japanese spotted fever (JSF).
METHODS: Patients with JSF enrolled in the Japanese Diagnosis Procedure Combination database from July 2010 to March 2021 were included in the analysis. Patients who received tetracycline on the day of admission were compared with those who received tetracycline later during their hospital stay using inverse probability of treatment weighting. The primary outcome was in-hospital mortality. Secondary outcomes were total hospitalization cost and length of hospital stay.
RESULTS: A total of 1360 patients were included, of whom 1060 (78%) received tetracycline on the day of admission (early tetracycline group), and 300 (22%) received tetracycline later (delayed tetracycline group). Patients in the delayed tetracycline group had significantly higher in-hospital mortality than those in the early tetracycline group (3.9% vs 1.4%; odds ratio, 2.94; 95% CI, 1.34-6.47), significantly higher hospitalization costs, and longer hospital stays than those in the early tetracycline group.
CONCLUSIONS: The prognosis of patients with JSF is worse if tetracycline administration is delayed; therefore, physicians should initiate tetracycline on admission if JSF is suspected as a possible diagnosis.
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Watt G, Kantipong P, Jongsakul K, Watcharapichat P, Phulsuksombati D, Strickman D.
Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial.
Lancet. 2000 Sep 23;356(9235):1057-61. doi: 10.1016/S0140-6736(00)02728-8.
Abstract/Text
BACKGROUND: Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus.
METHODS: Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C).
FINDINGS: About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy.
INTERPRETATION: Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.
