Scrub typhus, which is caused by Orientia tsutsugamushi, is a systemic illness that causes generalized vasculitis. The central nervous system (CNS) is the most crucial target in other rickettsial diseases; however, there have been several reports of encephalitis or meningitis without direct evidence of rickettsial invasion of the CNS in cases of scrub typhus. To investigate CNS involvement in cases of scrub typhus, we analyzed the CSF profiles (cell count and levels of protein and glucose) and amplified rickettsial DNA in CSF specimens by means of nested polymerase chain reaction (PCR) for 25 patients with the infection. Mild pleocytosis was present in 48% of the patients: CSF white blood cell counts ranged from 0 to 110/mm3 (mean [+/- SD] count, 16.3 +/- 27.0/mm3), and the mean (+/- SD) lymphocyte proportion was 51.9% +/- 23.9%. The CSF protein level was increased (>50 mg/dL) in seven patients. Nested PCR amplified six products from the 25 CSF specimens: four of the products were Boryong genotypes, and two were Karp genotypes. The results of this study suggest that O. tsutsugamushi does invade the CSF and that scrub typhus should be considered one of the causes of mononuclear meningitis in areas of endemicity.

The association of the cytoskeleton with the cadherin-catenin complex is essential for strong cell-cell adhesion in epithelial cells. In this study, we have investigated the effect of microtubule organization on cell-cell adhesion in differentiating keratinocytes. When microtubules of normal human epidermal keratinocytes (NHEKs) grown in low calcium media (0.05 mM) were disrupted with nocodazole or colcemid, cell-cell adhesion was induced through relocalization of the Ecadherin-catenin-actin complex to the cell periphery. This was accompanied by actin polymerization. Also, it was found that microtubule disruption-induced cell-cell adhesion was significantly reduced in more advanced differentiated keratinocytes. For example, when NHEK cells cultured under high calcium (1.2 mM) for 8 d and then in low calcium for 1 d were treated with nocodazole, there was no induction of cell-cell adhesion. Also long-term treatment of a phorbol ester for 48 h inhibited nocodazole-induced cell-cell adhesion of NHEK. Furthermore, this nocodazole-induced cell-cell adhesion could be observed in squamous cancer cell lines (A431 and SCC-5, -9, and -25) under low calcium condition, but not in the keratinocyte cell lines derived from normal epidermis (HaCaT, RHEK). On the other hand, HaCaT cells continuously cultivated in low calcium media regained a less differentiated phenotype such as decreased expression of cytokeratin 10, and increased K5; these changes were accompanied with inducibility of cell-cell adhesion by nocodazole. Together, our results suggest that microtubule disruption can induce the cell-cell adhesion via activation of endogenous E-cadherin in non-or early differentiating keratinocytes. However, this is no longer possible in advanced terminally differentiating keratinocytes, possibly due to irreversible changes effected by cell envelope barrier formation.

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Detection ofOrientia tsutsugamushi DNA in individual using polymerase chain reaction