Human granulocytic anaplasmosis in Kinmen, an offshore island of Taiwan

Abstract

Human granulocytic anaplasmosis, a tick-borne infection caused by Anaplasma phagocytophilum, has received scant attention, while scrub typhus, a mite-transmitted disease caused by Orientia tsutsugamushi, is the most common rickettsiosis in Taiwan. The clinical presentations of both diseases are characterized by undifferentiated fever, headache and malaise. Moreover, both pathogens have been detected in small mammals that serve as hosts for chiggers and ticks in the wild. The objective of the present study was to investigate whether human granulocytic anaplasmosis occurs in Taiwan. Blood samples from 274 patients suspected of having scrub typhus in Kinmen, an offshore island of Taiwan, in 2011 and 2012 were retrospectively examined by immunofluorescence assays. IgG antibodies reactive with Anaplasma phagocytophilum was found in 31.8% (87/274) of the patients. Paired serology identified 3 patients with human granulocytic anaplasmosis and 8 patients with coinfection with O. tsutsugamushi and A. phagocytophilum. Laboratory tests showed that elevated serum ALT/AST, creatinine, and BUN levels were observed in patients with anaplasmosis and coinfection, but elevated serum CRP levels, thrombocytopenia, and anemia were only observed in coinfected patients. PCR detected A. phagocytophilum 16S rDNA and p44/msp2 in 2 patients. The phylogenetic analysis suggested that the replicons of the 16S rDNA shared high sequence similarity with the reference sequences in the Korea, USA, Japan, and China. The amplicons of p44/msp2 were close to those of the human variants identified in the USA and Japan. Our findings indicated that A. phagocytophilum infection was prevalent but unrecognized in Taiwan. Human granulocytic anaplasmosis is a tick-borne rickettsial infection caused by Anaplasma phagocytophilum. Although most cases resolve readily, life-threatening complications can occur without prompt antibiotic treatment. The major difficulty in diagnosing human granulocytic anaplasmosis is due to the nonspecific nature of the symptoms. Given that scrub typhus is the most frequently reported rickettsial disease in Taiwan and shares similar early clinical signs with anaplasmosis, we retrospectively examined blood samples from patients with suspected diagnoses of scrub typhus in 2011 and 2012. While serological evidence of potential past exposure was found in as many as 31.8% (87/274) of the patients, current or recent anaplasmosis was supported by seroconversion in 11 patients, including 8 patients coinfected with scrub typhus. Anaplasma phagocytophilum DNA was detected in acute phase samples, and the amplified fragments were phylogenetically close to those of variants in the Korea, the USA, Japan, and China. Herein, for the first time, we confirmed the presence of human granulocytic anaplasmosis in Taiwan. By reporting coinfections with anaplasmosis and scrub typhus, the study further highlighted the health risk of increasing contact with wild rodents.