Clinical study of Japanese spotted fever and its aggravating factors

Abstract

Twenty-eight patients with Japanese spotted fever were clinically investigated. The diagnosis was determined by confirming an increase of specific antibody. All patients were treated with minocycline, and all recovered, excluding one patient with a fulminant course. Fever and exanthema were observed in all patients, and an eschar was pointed out in 20 (71%) patients. The platelet count was 10 x 10(4)/microl or lower in 8 (28%) patients. The fibrin degradation product (FDP)-level was abnormally high, 10 microg/ml or more, in 16 (57%) patients. The creatine kinase (CK) value was high in 14 of 22 patients, suggesting the presence of myositis. The leukocyte count, FDP, C-reactive protein, and soluble interleukin 2 receptor (sIL2-R) levels were significantly higher in severe cases. In the group without concomitant steroid therapy, mean times of 54.7 h and 101.4 h were required to reduce the temperature to 38 degrees C and 37 degrees C or lower, respectively, after the initiation of tetracycline treatment. There were 6 severe cases: 1 with disseminated intravascular coagulation, 2 with multiorgan failure, 1 with acute respiratory distress syndrome, and 2 with meningoencephalitis. These severe cases formed a group that required 6 or more days to initiate therapy after the onset (P < 0.005 vs non-severe group), showing that delay in diagnosis and therapy is the major cause of aggravation. In the 2 patients complicated by multiorgan failure, the sIL2-R level, produced by activated lymphocytes, was 10,000 U/ml or higher, suggesting that an sIL2-R level of more than 10,000 U/ml can be used as a marker of poor prognosis. It may be better that moderate to severe cases are treated with minocycline plus short-term steroid therapy.

Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

“…We estimate that hypercytokinemia may contribute to the disease severity of rickettsiosis, including JSF. For instance, fulminant TD has been associated with hemophagocytic syndrome (10), and this syndrome may represent a hyperreaction of the immune system mediated by an overactivated cytokine network during the advanced stages of rickettsial infection (19,(26)(27)(28). We previously reported that a downregulation of these cytokines and chemokines is observed after the administration of tetracyclines, demonstrated a correlation between the severity of TD and the serum concentration of TNF-␣ in the acute phase of the disease, and showed that TNF-␣ levels are predictive of the severity of TD (18,19,29,30).…”

Tick- and flea-borne rickettsial emerging zoonoses

“…Between 1984 and 2004, nine more species or subspecies of tick-borne spotted fever rickettsiae were identified as emerging pathogens throughout the world, including, R. japonica in Japan [6,46,65,71,72,[82][83][84]146]; "R. conorii caspia" in Astrakhan [35,38,39,143], Africa [47] and Kosovo [48]; R. africae in sub-Saharan Africa and the West Indies [62,63]; R. honei in the Flinders Island, offshore of Australia [9,57,140,141], the Island of Tasmania, Australia [153], Thailand [73], and possibly in the USA [13]; R. slovaca in Europe [29,74,101,122]; "R. sibirica mongolotimonae" in China [157], Europe [44,118] and Africa [106,113]; R. heilongjiangensis in China [42,49]; R. aeschlimannii in Africa [11,112,121] and Europe [43]; and finally R. parkeri in the USA [104]. R. helvetica is also suspected to be a human pathogen in Europe [45] and Asia [46,61,107], but this needs c...…”

“…Tick-borne SFG rickettsioses range from mild to severe and fatal disease. To date, no mortalities or severe complications have been reported in patients with African tick-bite fever caused by R. africae [62], whereas severe disease, including one fatal case, has been reported with Japanese spotted fever rickettsioses [6,71,72,84].…”

Severe Japanese Spotted Fever Successfully Treated with Fluoroquinolone

“…Fluoroquinolones may be needed to completely eradicate the causative rickettsiae. Moreover, fluoroquinolones should be administered as soon as antibiotics are deemed ineffective and rickettsial diseases are strongly suspected, because some spotted fever-type rickettsial diseases including Japanese spotted fever, can be fatal (1,2,13).…”

“…For several days after1984, severe cases have been sporadically reported, however, most cases were cured by tetracyclines (1)(2)(3). Kodama et al reported twenty-eight patients with Japanese spotted fever were treated with minocycline, and all recovered, excluding one patient with a severe course (2). We encountered a patient with severe Japanese spotted fever who was not cured by tetracycline, but treated successfully with fluoroquinolone.…”