Dong-Min Kim, Kyung Jun Won, Chi Young Park, Ki Dong Yu, Hyong Sun Kim, Tae Young Yang, Ji Hyun Lee, Hyun Kuk Kim, Hyeon-Je Song, Seung-Hyun Lee, Ho Shin
Distribution of eschars on the body of scrub typhus patients: a prospective study.
Am J Trop Med Hyg. 2007 May;76(5):806-9.
Abstract/Text
Eschar is an important finding for the diagnosis of scrub typhus. The IFA test for possible scrub typhus was performed. The presence or absence of eschar was thoroughly examined. Among the 176 scrub typhus cases confirmed by IFA, 162 (92.0%) cases had eschar; 128 patients (79.5%) had eschars on the front of the body. Eschars were primarily detected in males within 30 cm below the umbilicus (19 patients, 35.8%). Distributions on the lower extremities and the front chest above the umbilicus were 22.6% (12 patients) and 20.8% (11 patients), respectively. A different pattern was seen in females. The most prevalent area was the front chest above the umbilicus, which accounted for 40.7% (44 patients) of all the detected eschars. Our study is the first report of a schematic diagram that shows the differences between the males and females with respect to eschar location in scrub typhus patients.
Winsley Rose, Roshni J Rajan, Anu Punnen, Urmi Ghosh
Distribution of Eschar in Pediatric Scrub Typhus.
J Trop Pediatr. 2016 Apr 27;. doi: 10.1093/tropej/fmw027. Epub 2016 Apr 27.
Abstract/Text
BACKGROUND: Identifying an eschar in scrub typhus is useful for initiation of prompt and appropriate antibiotic therapy.
METHODS: The distribution of eschars in all children <15 years of age admitted with confirmed scrub typhus over a 5 year period is described.
RESULTS: Of 431 children admitted with scrub typhus, eschars were present in 176 (40.8%) children with the following distribution: head, face and neck, 33 (19.1%); axillae, 37 (21%); chest and abdomen, 21 (11.9%); genitalia, inguinal region and buttocks, 58 (33%); back, 8 (4.5%); upper extremities, 13 (7.4%); and lower extremities, 5 (2.8%). The commonest sites of eschars were scrotum (27 of 106; 25.5%) and axillae (15 of 106; 14.2%) in males and axillae (22 of 70; 31.4%) and groin (16 of 70; 22.9%) in females. Eschars were seen within skin folds in 100 of 176 (56.8%) children.
CONCLUSION: Children should be carefully examined for the presence of eschar especially in the skin folds of the genitalia, axillae and groin to make an early diagnosis of scrub typhus.
© The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Eiichiro Sando, Motoi Suzuki, Shungo Katoh, Hiromi Fujita, Masakatsu Taira, Makito Yaegashi, Koya Ariyoshi
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.
Stuart D Blacksell, Cherry Lim, Ampai Tanganuchitcharnchai, Suthatip Jintaworn, Pacharee Kantipong, Allen L Richards, Daniel H Paris, Direk Limmathurotsakul, Nicholas P J Day
Optimal Cutoff and Accuracy of an IgM Enzyme-Linked Immunosorbent Assay for Diagnosis of Acute Scrub Typhus in Northern Thailand: an Alternative Reference Method to the IgM Immunofluorescence Assay.
J Clin Microbiol. 2016 Jun;54(6):1472-8. doi: 10.1128/JCM.02744-15. Epub 2016 Mar 23.
Abstract/Text
The enzyme-linked immunosorbent assay (ELISA) has been proposed as an alternative serologic diagnostic test to the indirect immunofluorescence assay (IFA) for scrub typhus. Here, we systematically determine the optimal sample dilution and cutoff optical density (OD) and estimate the accuracy of IgM ELISA using Bayesian latent class models (LCMs). Data from 135 patients with undifferentiated fever were reevaluated using Bayesian LCMs. Every patient was evaluated for the presence of an eschar and tested with a blood culture for Orientia tsutsugamushi, three different PCR assays, and an IgM IFA. The IgM ELISA was performed for every sample at sample dilutions from 1:100 to 1:102,400 using crude whole-cell antigens of the Karp, Kato, and Gilliam strains of O. tsutsugamushi developed by the Naval Medical Research Center. We used Bayesian LCMs to generate unbiased receiver operating characteristic curves and found that the sample dilution of 1:400 was optimal for the IgM ELISA. With the optimal cutoff OD of 1.474 at a sample dilution of 1:400, the IgM ELISA had a sensitivity of 85.7% (95% credible interval [CrI], 77.4% to 86.7%) and a specificity of 98.1% (95% CrI, 97.2% to 100%) using paired samples. For the ELISA, the OD could be determined objectively and quickly, in contrast to the reading of IFA slides, which was both subjective and labor-intensive. The IgM ELISA for scrub typhus has high diagnostic accuracy and is less subjective than the IgM IFA. We suggest that the IgM ELISA may be used as an alternative reference test to the IgM IFA for the serological diagnosis of scrub typhus.
Copyright © 2016 Blacksell et al.
Dong-Min Kim, Hyun Lee Kim, Chi Young Park, Tae Young Yang, Ji Hyun Lee, Jong Tae Yang, Soo-Kyoung Shim, Seung-Hyun Lee
Clinical usefulness of eschar polymerase chain reaction for the diagnosis of scrub typhus: a prospective study.
Clin Infect Dis. 2006 Nov 15;43(10):1296-300. doi: 10.1086/508464. Epub 2006 Oct 12.
Abstract/Text
BACKGROUND: The aim of this study was to determine the diagnostic utility of performing eschar polymerase chain reaction (PCR) for the diagnosis of scrub typhus through a prospective comparison of eschar PCR results with indirect immunofluorescent antibody assay (IFA) results.
METHODS: We conducted a multicenter prospective study involving patients with possible scrub typhus. Whole-blood samples and eschars were obtained for serological evaluation and PCR. A new crust was formed several days later at the site of the removed eschar. The newly formed crust was taken for performance of the second eschar PCR. Additional blood samples and eschars were collected, if possible, at 1-week intervals for 1 month after antibiotic treatment.
RESULTS: We prospectively studied 135 patients with possible scrub typhus. Of these patients, 118 had scrub typhus confirmed on the basis of either a single indirect immunofluorescent specific immunoglobulin M titer against Orientia tsutsugamushi of > or = 1:10 or a > or = 4-fold increase in the follow-up titer. The results of nested PCR assay of the eschars demonstrated a sensitivity of 0.86 (95% confidence interval, 0.78-0.92) and a specificity of 1 (95% confidence interval, 0.05-1). Among the 50 patients who showed positive results of eschar PCR at admission, 46 (92%) also showed positive results for the follow-up PCR test of the newly formed eschar after the treatment with antibiotics.
CONCLUSIONS: The eschar PCR assay was useful as a rapid and reliable test to confirm the diagnosis of scrub typhus, even though the patients received treatment with appropriate antibiotics, such as macrolides, quinolones, and tetracycline, which are all active against Orientia and Rickettsia species.
Andrew J Taylor, Daniel H Paris, Paul N Newton
A Systematic Review of Mortality from Untreated Scrub Typhus (Orientia tsutsugamushi).
PLoS Negl Trop Dis. 2015;9(8):e0003971. doi: 10.1371/journal.pntd.0003971. Epub 2015 Aug 14.
Abstract/Text
BACKGROUND: Scrub typhus, a bacterial infection caused by Orientia tsutsugamushi, is increasingly recognized as an important cause of fever in Asia, with an estimated one million infections occurring each year. Limited access to health care and the disease's non-specific symptoms mean that many patients are undiagnosed and untreated, but the mortality from untreated scrub typhus is unknown. This review systematically summarizes the literature on the untreated mortality from scrub typhus and disease outcomes.
METHODOLOGY/PRINCIPAL FINDINGS: A literature search was performed to identify patient series containing untreated patients. Patients were included if they were symptomatic and had a clinical or laboratory diagnosis of scrub typhus and excluded if they were treated with antibiotics. The primary outcome was mortality from untreated scrub typhus and secondary outcomes were total days of fever, clinical symptoms, and laboratory results. A total of 76 studies containing 89 patient series and 19,644 patients were included in the final analysis. The median mortality of all patient series was 6.0% with a wide range (min-max) of 0-70%. Many studies used clinical diagnosis alone and had incomplete data on secondary outcomes. Mortality varied by location and increased with age and in patients with myocarditis, delirium, pneumonitis, or signs of hemorrhage, but not according to sex or the presence of an eschar or meningitis. Duration of fever was shown to be long (median 14.4 days Range (9-19)).
CONCLUSIONS: Results show that the untreated mortality from scrub typhus appears lower than previously reported estimates. More data are required to clarify mortality according to location and host factors, clinical syndromes including myocarditis and central nervous system disease, and in vulnerable mother-child populations. Increased surveillance and improved access to diagnostic tests are required to accurately estimate the untreated mortality of scrub typhus. This information would facilitate reliable quantification of DALYs and guide empirical treatment strategies.
Nelson Lee, Margaret Ip, Bonnie Wong, Grace Lui, Owen Tak Yin Tsang, Jak Yiu Lai, Kin Wing Choi, Rebecca Lam, Tak Keung Ng, Jenny Ho, Yin Yan Chan, Clive S Cockram, Sik To Lai
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.
G Watt, P Kantipong, K Jongsakul, P Watcharapichat, D Phulsuksombati, D Strickman
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.
Yeon-Sook Kim, Hwan-Jung Yun, Soo Kyoung Shim, Sun Hoe Koo, Sun Young Kim, Samyong Kim
A comparative trial of a single dose of azithromycin versus doxycycline for the treatment of mild scrub typhus.
Clin Infect Dis. 2004 Nov 1;39(9):1329-35. doi: 10.1086/425008. Epub 2004 Oct 11.
Abstract/Text
BACKGROUND: Scrub typhus is one of the most important endemic infections in the Asia-Pacific region. Although tetracyclines or chloramphenicol are the recommended drugs of choice for the treatment of scrub typhus, reports of doxycycline-resistant strains have prompted a search for alternative treatments.
METHODS: We conducted a prospective, open-label, randomized trial from September 2002 through November 2003 to compare azithromycin with doxycycline for the treatment of mild scrub typhus. The time to defervescence was assessed to compare the efficacy of the 2 treatment regimens.
RESULTS: A total of 93 patients were randomly assigned to receive either a single 500-mg dose of azithromycin or a 1-week course of daily oral 200-mg dose of doxycycline. Cure was achieved in 47 (100%) of 47 patients in the azithromycin-treated group and in 43 (93.5%) of 46 patients in the doxycycline-treated group (P=.117). The median time to defervescence was 21 h for the azithromycin-treated group and 29 h for the doxycycline-treated group (P=.097). There were no serious adverse events during the study. No relapses occurred in either group during a 1-month follow-up period.
CONCLUSION: The single 500-mg dose of azithromycin was as effective as the 1-week course of daily 200-mg doses of doxycycline for the treatment of mild scrub typhus acquired in South Korea.
B A Cunha, J Baron, C B Cunha
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.
George M Varghese, Divya Dayanand, Karthik Gunasekaran, Debasree Kundu, Mukta Wyawahare, Navneet Sharma, Dhruva Chaudhry, Sanjay K Mahajan, Kavitha Saravu, Blessed W Aruldhas, Binu S Mathew, Roshini G Nair, Nalini Newbigging, Aswathy Mathew, Kundavaram P P Abhilash, Manisha Biswal, Ann H Prasad, Anand Zachariah, Ramya Iyadurai, Samuel G Hansdak, Sowmya Sathyendra, Thambu D Sudarsanam, John A J Prakash, Abi Manesh, Alladi Mohan, Joel Tarning, Stuart D Blacksell, Pimnara Peerawaranun, Naomi Waithira, Mavuto Mukaka, Phaik Yeong Cheah, John V Peter, Ooriapadickal C Abraham, Nicholas P J Day, INTREST Trial Investigators
Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.
N Engl J Med. 2023 Mar 2;388(9):792-803. doi: 10.1056/NEJMoa2208449.
Abstract/Text
BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear.
METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5.
RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups.
CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).
Copyright © 2023 Massachusetts Medical Society.
Wiwit Tantibhedhyangkul, Emmanouil Angelakis, Narongchai Tongyoo, Paul N Newton, Catrin E Moore, Rattanaphone Phetsouvanh, Didier Raoult, Jean-Marc Rolain
Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi.
Int J Antimicrob Agents. 2010 Apr;35(4):338-41. doi: 10.1016/j.ijantimicag.2009.11.019.
Abstract/Text
Scrub typhus is a public health concern for a population of over a billion humans, with an estimated incidence of one million cases/year in endemic areas. Although doxycycline remains the standard therapy, fluoroquinolones have been used successfully in a few patients. However, there is also clinical evidence that fluoroquinolones are ineffective in the treatment of scrub typhus. To clarify this matter, we determined the in vitro susceptibility of Orientia tsutsugamushi strain Kato to ciprofloxacin and ofloxacin and sequenced the quinolone resistance-determining region (QRDR) of the gyrA gene, the target of fluoroquinolones, of 18 fresh isolates from the Lao PDR. Orientia tsutsugamushi strain Kato was resistant to ciprofloxacin and ofloxacin in vitro (minimum inhibitory concentration=8 microg/mL). All sequences obtained, including those from the two available genomes of O. tsutsugamushi (strains Boryong and Ikeda), had a Ser83Leu mutation in their QRDR domain that is known to be associated with fluoroquinolone resistance. These findings re-emphasise the usefulness of in silico analysis for the prediction of antibiotic resistance and suggest that fluoroquinolones should not be used in the treatment of scrub typhus.
(c) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Hee-Chang Jang, Su-Mi Choi, Mi-Ok Jang, Joon-Hwan Ahn, Uh-Jin Kim, Seung-Ji Kang, Jong-Hee Shin, Hyon E Choy, Sook-In Jung, Kyung-Hwa Park
Inappropriateness of quinolone in scrub typhus treatment due to gyrA mutation in Orientia tsutsugamushi Boryong strain.
J Korean Med Sci. 2013 May;28(5):667-71. doi: 10.3346/jkms.2013.28.5.667. Epub 2013 May 2.
Abstract/Text
The use of quinolone for treatment of rickettsial diseases remains controversial. Recent clinical studies suggest that quinolone is not as effective as others in patients with rickettsial diseases including scrub typhus, although the mechanism is not well understood. In this study, we evaluated the mutation in gyrA associated with quinolone resistance. We prospectively enrolled scrub typhus patients, collected blood samples and clinical data from October, 2010 to November, 2011. Among the 21 patients enrolled, one initially received ciprofloxacin for 3 days but was switched to doxycycline due to clinical deterioration. We obtained the gyrA gene of Orientia tsutsugamushi from 21 samples (20 Boryong strain, 1 Kato strain) and sequenced the quinolone resistance-determining region. All of 21 samples had the Ser83Leu mutation in the gyrA gene, which is known to be associated with quinolone resistance. This suggests that quinolones may be avoided for the treatment of serious scrub typhus.
Yeon-Sook Kim, Hyo Jin Lee, Meayoung Chang, Sung Kyong Son, Yun Ee Rhee, Soo Kyong Shim
Scrub typhus during pregnancy and its treatment: a case series and review of the literature.
Am J Trop Med Hyg. 2006 Nov;75(5):955-9.
Abstract/Text
Although scrub typhus is uncommon in pregnant women, when present, it can have serious repercussions for the mother and developing fetus. Since it is uncommon, the clinical impact of scrub typhus on pregnancy has not been elucidated and an effective and safe therapeutic regimen has not been validated. The medical records of pregnant women whose scrub typhus were treated at Chungnam National University Hospital were reviewed and their clinical outcomes were evaluated. A review of the literature was also performed on pregnant women with scrub typhus and their clinical outcomes. Eight pregnant women with scrub typhus were treated successfully with a single 500-mg dose of azithromycin, and no relapses were reported. They all delivered healthy babies at term, without congenital or neonatal complications. In the reviews, azithromycin was effective against scrub typhus and had favorable pregnancy outcomes. Ciprofloxacin and cefuroxime failed to treat scrub typhus and fetal loss resulted. A single 500-mg dose of azithromycin may be a reasonable treatment regimen for pregnant women with scrub typhus. Ciprofloxacin might not be advisable for the treatment of scrub typhus during pregnancy. Scrub typhus itself seems to have serious adverse effects on pregnancy if not appropriately controlled.
Kriangsak Phimda, Siriwan Hoontrakul, Chuanpit Suttinont, Sompong Chareonwat, Kitti Losuwanaluk, Sunee Chueasuwanchai, Wirongrong Chierakul, Duangjai Suwancharoen, Saowaluk Silpasakorn, Watcharee Saisongkorh, Sharon J Peacock, Nicholas P J Day, Yupin Suputtamongkol
Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus.
Antimicrob Agents Chemother. 2007 Sep;51(9):3259-63. doi: 10.1128/AAC.00508-07. Epub 2007 Jul 16.
Abstract/Text
Leptospirosis and scrub typhus are important causes of acute fever in Southeast Asia. Options for empirical therapy include doxycycline and azithromycin, but it is unclear whether their efficacies are equivalent. We conducted a multicenter, open, randomized controlled trial with adult patients presenting with acute fever (<15 days), without an obvious focus of infection, at four hospitals in Thailand between July 2003 and January 2005. Patients were randomly allocated to receive either a 7-day course of doxycycline or a 3-day course of azithromycin. The cure rate, fever clearance time, and adverse drug events were compared between the two study groups. A total of 296 patients were enrolled in the study. The cause of acute fever was determined for 151 patients (51%): 69 patients (23.3%) had leptospirosis; 57 patients (19.3%) had scrub typhus; 14 patients (4.7%) had murine typhus; and 11 patients (3.7%) had evidence of both leptospirosis and a rickettsial infection. The efficacy of azithromycin was not inferior to that of doxycycline for the treatment of both leptospirosis and scrub typhus, with comparable fever clearance times in the two treatment arms. Adverse events occurred more frequently in the doxycycline group than in the azithromycin group (27.6% and 10.6%, respectively; P = 0.02). In conclusion, doxycycline is an affordable and effective choice for the treatment of both leptospirosis and scrub typhus. Azithromycin was better tolerated than doxycycline but is more expensive and less readily available.
Holly M Biggs, Casey Barton Behravesh, Kristy K Bradley, F Scott Dahlgren, Naomi A Drexler, J Stephen Dumler, Scott M Folk, Cecilia Y Kato, R Ryan Lash, Michael L Levin, Robert F Massung, Robert B Nadelman, William L Nicholson, Christopher D Paddock, Bobbi S Pritt, Marc S Traeger
Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis - United States.
MMWR Recomm Rep. 2016 May 13;65(2):1-44. doi: 10.15585/mmwr.rr6502a1. Epub 2016 May 13.
Abstract/Text
Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.
