this study was conducted at e - da hospital , a teaching hospital located in kaohsiung county in southern taiwan , and approved by its institute ethics committee ( e - mrp-096 - 065 ) in 2006 . rickettsial diseases are notifiable diseases in taiwan , and suspected cases with appropriate clinical characteristics are reported to the center for disease control , taipei , taiwan for confirmation . because acute q fever , scrub typhus , and murine typhus ( caused by flea - borne rickettsia typhi ) are the most common rickettsial diseases in taiwan ( 35 ) , we requested tests for the etiologic agents of the 3 diseases simultaneously in patients who sought treatment , regardless of which disease we suspected on the basis of clinical features . serologic assessments for specific antibodies to c. burnetii and o. tsutsugamushi were performed by using indirect immunofluorescence antibody assay as previously described ( 5 ) . acute q fever was diagnosed by either an antiphase ii antigen immunoglobulin ( ig ) g titer > 320 and antiphase ii antigen igm titer > 80 in a single serum sample , or a > 4-fold rise of antiphase ii antigen igg titer in paired serum samples . antigens of 3 major strains of o. tsutsugamushi ( karp , kato , and gilliam strains ) were used to diagnose scrub typhus : either an igm titer > 80 or a > 4-fold rise in igg titer in paired serum samples for karp , kato , and gilliam strains of o. tsutsugamushi . murine typhus was diagnosed by an igm titer > 80 or a > 4-fold rise in igg titer against r. typhi in paired sera . co - infection with c. burnetii and o. tsutsugamushi was diagnosed if the serologic results fulfilled the diagnostic criteria for both infections . from april 15 , 2004 , through june 30 , 2008 , we identified 12 cases of murine typhus , 89 cases of acute q fever , and 43 cases of scrub typhus ; 5 persons had both acute q fever and scrub typhus . all 5 patients with co - infections denied having fever within 3 months before admission . the demographic data and clinical manifestations of the 5 case - patients co - infected with c. burnetii and o. tsutsugamushi are listed in the appendix table ) . in this study , we found that 5.3% ( 5/94 ) and 10.4% ( 5/48 ) patients who fulfilled the serologic diagnosis of acute q fever and scrub typhus , respectively , were co - infected with c. burnetii and o. tsutsugamushi . although the major arthropod vectors , animal reservoirs , and route of transmission to humans are different for c. burnetii and o. tsutsugamushi , co - infection with these 2 organisms can occur , particularly in regions where both q fever and scrub typhus are endemic , such as southern taiwan . identification of co - infection improves understanding of the epidemiology of each disease and reminds clinicians to monitor patients for whom the development of chronic q fever after acute q fever is a high risk ; such follow - up is not needed for the cases of scrub typhus alone . few cases of concurrent q fever and other rickettsioses have been reported in the literature ( 6,7 ) . found that 6 patients with tick - borne rickettsioses had concomitant or consecutive infection with c. burnetii ; antibodies were routinely tested against antigens of c. burnetii , rickettsia spp . , anaplasma phagocytophylum , francisella tularensis , and borrelia burgdorferi ( 6 ) . five and 2 of their 6 patients had an eschar and skin rash , respectively , and none had a history or clinical signs suggestive of acute q fever . in contrast , none of our patients had an eschar , the characteristic manifestation of scrub typhus , and only 1 had a skin rash , which made a presumptive clinical diagnosis of scrub typhus difficult . co - infection with o. tsutsugamushi and leptospira spp . tends to be associated with severe illness and death ( 812 ) , and cases are mainly reported in southeast asia , particularly in thailand ( 8) and taiwan ( 912 ) . however , we did not routinely test for leptospirosis in this study . cases of o. tsutsugamushi and r. typhi co - infection had been found in a surveillance of patients with fever of unknown causes , which were possibly cases of scrub typhus in china ( 13 ) . no co - infection of o. tsutsugamushi and r. typhi was identified in our study , which might be because relatively fewer cases of murine typhus were identified . in the 6 patients with tick - borne rickettsioses and c. burnetii coinfection reported by rolain et al . , 3 patients likely had concomitant infection caused by tick bites and the other 3 were possibly consecutive infections ( 6 ) . it was difficult to identify concomitant or consecutive infection in our patients because we could not determine a definite time when patients were bitten by arthropod vectors , had contact with animal reservoirs , or were exposed to the environments abundant in c. burnetii and o. tsutsugamushi . with the assessment of serologic results , however , case - patients 3 , 4 , and 5 might have acquired scrub typhus first and later been infected with c. burnetii ; titers of igm and igg against o. tsutsugamushi were high , and antibodies against c. burnetii phase ii antigen were negative on first tests in case - patients 4 and 5 ( appendix table ) . in case - patient 3 who sought treatment for fever 20 days before admission , the antibody titers for c. burnetii phase ii antigen and o. tsutsugamushi were rising and declining , respectively , in paired serum samples tested . case - patient 2 might have had q fever first and scrub typhus later because the first serum tests were positive for c. burnetii phase ii igm and igg , but negative for o. tsutsugamushi antibodies . for case - patient 1 , the rising antibody titers to both pathogens in paired serum specimens suggest a concomitant infection . because chiggers were rarely reported as arthropod reservoirs of c. burnetii , we believe that our patients might have acquired dual infection through different routes . the possibility of serologic cross - reaction between q fever and scrub typhus that results in misdiagnosis of co - infection is low . , legionella pneumophila , l. micdadei , and ehrlichia chaffeensis have been reported , but there were no data available on cross - reactivity for o. tsutsugamushi ( 6,14 ) . in conclusion , although major arthropod vectors , animal reservoirs , and routes of transmission to humans are different for c. burnetii and o. tsutsugamushi , co - infection with these 2 organisms may occur , particularly in regions where both q fever and scrub typhus are endemic . clinical characteristics and results of examinations of 5 patients with acute q fever and scrub typhus , taiwan *
acute q fever and scrub typhus are zoonoses endemic to southern taiwan . among the 137 patients with acute q fever ( 89 , 65.0% ) or scrub typhus ( 43 , 31.4% ) 
 , we identified 5 patients ( 3.6% ) who were co - infected with coxiella burnetii and orientia tsutsugamushi .