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Trop Doct OnlineFirst, published on April 13, 2015 as doi:10.1177/0049475515579772
Article
Clinical and laboratory features parameters of human granulocytic anaplasmosis (HGA) in patients admitted to hospital in Guangdong Province, China
Tropical Doctor 0(0) 1–5 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0049475515579772 tdo.sagepub.com
Xiao-yang Jiao1, Zhi-chen Fan2, Ya-zhen Li2, Yue-ting Tang1 and Chang-wen Ke1,3
Abstract Background: Human granulocytic anaplasmosis (HGA) is an acute tick-borne infectious disease with increasing morbidity and mortality, but is rarely considered in clinical practice. Because human-to-human transfusion or nosocomial transmission can occur, diagnosis is difficult when the history of tick bites is not clear. Methods: We present clinical features and laboratory data of HGA patients who had no clear tick bite history. Results: All patients in the study presented with a high fever, petechiae, purpura, nose bleeding and leukopenia, and patients had abnormally high levels of serum ferritin and C-reactive protein. Morulae in leukocytes were observed in three patients. Foamy histiocytes and slight erythrophagocytic activity were only found in severely ill patients. Conclusion: In patients with fever and thrombocytopenia in whom no other diagnosis is evident on clinical assessment, HGA should be considered in the differential diagnosis, and tested for serologically if possible. For patients in whom the diagnosis of HGA is possible, and to whom tetracyclines can safely be given, it is apparent that these drugs hasten recovery and improve the prognosis.
Keywords Human granulocytic anaplasmosis, clinical characteristics, thrombocytopenia
Background Human granulocytic anaplasmosis (HGA) is an acute infectious disease caused by Anaplasma phagocytophilum (also called Ehrlichia phagocytophila, Ehrlichia equi and the human granulocytic ehrlichiosis agent), which is an emerging tick-borne pathogen in humans and animals worldwide.1 Nowadays, HGA is the third most common vector-borne infection in the USA and Europe, and is increasingly recognised as an important vector-borne infection in Asia. In USA, the seroprevalence is in the range of 0.6–14.9%,2 in 3.5% of blood donors and 4.2% of whom reported having been bitten by a tick.3 In Europe, the seroprevalence is in the range of 1.4–21%.1 In Asia, 1.8% of Korean patients with febrile illness had antibodies to A. phagocytophilum.4 The first HGA case in China was found in Anhui Province in 2006.5 Since then, at least 557 people, distributed across provinces Hubei, Henan, Anhui, Shandong, Helongjiang, Inner Mongolia, Xingjiang and Tianjin, have been found to be infected and 18 patients died in the past 5 years.5 Seroprevalence
studies showed that 8.8% of farm workers had positive antibodies in northern China,6 and these were detected in 20% of those at high risk of tick exposure in central and southeastern China.7 Recently, the morbidity and mortality associated with HGA in China has led to public health concern.8 The clinical presentation of HGA consists of high fever (>38.5 C), headache, malaise, myalgia and/or arthralgia, and is often accompanied by leukopenia, 1
PhD, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong Province, PR China 2 MS, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong Province, PR China 3 Professor, Department of Cell Biology and Genetics, Shantou University Medical College, Shantuo, Guangdong Province, PR China; Institute of Microbiology, Center for Diseases Control and Prevention of Guangdong Province, PR China Corresponding author: Chang-wen Ke, Institute of Microbiology, Center for Diseases Control and Prevention of Guangdong Province, 176 Xin Gang West Road, Guangzhou 510300, PR China. Email: [email protected]
Downloaded from tdo.sagepub.com at University of British Columbia Library on July 28, 2015
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thrombocytopenia and increased hepatic enzymes.9 Clinically, the diagnosis of HGA may be difficult as non-specific symptoms, such as nausea, abdominal pain, diarrhoea and cough, proliferate. The combination of high fever and thrombocytopenia is found in several other diagnoses, including dengue, leptospirosis and haemorrhagic fever. It is suggested that HGA may be a major cause of unexplained fever during the tick season.10 However, it is rarely considered a possible pathogen in clinical practice, and its testing is not listed for routine diagnostic assessment. Thus, the actual number of cases may be considerably underestimated. Misdiagnosis and delayed antibiotic therapy will result in progressive deterioration of the patients. In China, mortality for HGA is much higher than that observed in the USA and Europe.11,12 The estimated HGA case fatality rate is believed to be low in China (range, 0.5–1%); but infection may be severe in the elderly or those immunocompromised.13 Active antibiotic therapy is advocated for all patients with confirmed HGA. Therefore, aetiology analyses are important, especially as HGA testing is not included in routine laboratory detection. In China, A. phagocytophilum is transmitted by the tick, Ixodes persulcatus.14 A history of prior tick bite is therefore an important clue, but most do not recall being bitten.15,16 Recently, nosocomial transmission has been documented through blood transfusion respiratory secretions.5,17 In our study, among sera of 133 patients with fever and thrombocytopenia, we found 30 infected by HGA.
Patients From March 2009 to September 2011, 133 patients with fever (>38.0 C) and thrombocytopenia (platelet counts
(TDO)
[1–5] [PREPRINTER stage]
Trop Doct OnlineFirst, published on April 13, 2015 as doi:10.1177/0049475515579772
Article
Clinical and laboratory features parameters of human granulocytic anaplasmosis (HGA) in patients admitted to hospital in Guangdong Province, China
Tropical Doctor 0(0) 1–5 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0049475515579772 tdo.sagepub.com
Xiao-yang Jiao1, Zhi-chen Fan2, Ya-zhen Li2, Yue-ting Tang1 and Chang-wen Ke1,3
Abstract Background: Human granulocytic anaplasmosis (HGA) is an acute tick-borne infectious disease with increasing morbidity and mortality, but is rarely considered in clinical practice. Because human-to-human transfusion or nosocomial transmission can occur, diagnosis is difficult when the history of tick bites is not clear. Methods: We present clinical features and laboratory data of HGA patients who had no clear tick bite history. Results: All patients in the study presented with a high fever, petechiae, purpura, nose bleeding and leukopenia, and patients had abnormally high levels of serum ferritin and C-reactive protein. Morulae in leukocytes were observed in three patients. Foamy histiocytes and slight erythrophagocytic activity were only found in severely ill patients. Conclusion: In patients with fever and thrombocytopenia in whom no other diagnosis is evident on clinical assessment, HGA should be considered in the differential diagnosis, and tested for serologically if possible. For patients in whom the diagnosis of HGA is possible, and to whom tetracyclines can safely be given, it is apparent that these drugs hasten recovery and improve the prognosis.
Keywords Human granulocytic anaplasmosis, clinical characteristics, thrombocytopenia
Background Human granulocytic anaplasmosis (HGA) is an acute infectious disease caused by Anaplasma phagocytophilum (also called Ehrlichia phagocytophila, Ehrlichia equi and the human granulocytic ehrlichiosis agent), which is an emerging tick-borne pathogen in humans and animals worldwide.1 Nowadays, HGA is the third most common vector-borne infection in the USA and Europe, and is increasingly recognised as an important vector-borne infection in Asia. In USA, the seroprevalence is in the range of 0.6–14.9%,2 in 3.5% of blood donors and 4.2% of whom reported having been bitten by a tick.3 In Europe, the seroprevalence is in the range of 1.4–21%.1 In Asia, 1.8% of Korean patients with febrile illness had antibodies to A. phagocytophilum.4 The first HGA case in China was found in Anhui Province in 2006.5 Since then, at least 557 people, distributed across provinces Hubei, Henan, Anhui, Shandong, Helongjiang, Inner Mongolia, Xingjiang and Tianjin, have been found to be infected and 18 patients died in the past 5 years.5 Seroprevalence
studies showed that 8.8% of farm workers had positive antibodies in northern China,6 and these were detected in 20% of those at high risk of tick exposure in central and southeastern China.7 Recently, the morbidity and mortality associated with HGA in China has led to public health concern.8 The clinical presentation of HGA consists of high fever (>38.5 C), headache, malaise, myalgia and/or arthralgia, and is often accompanied by leukopenia, 1
PhD, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong Province, PR China 2 MS, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong Province, PR China 3 Professor, Department of Cell Biology and Genetics, Shantou University Medical College, Shantuo, Guangdong Province, PR China; Institute of Microbiology, Center for Diseases Control and Prevention of Guangdong Province, PR China Corresponding author: Chang-wen Ke, Institute of Microbiology, Center for Diseases Control and Prevention of Guangdong Province, 176 Xin Gang West Road, Guangzhou 510300, PR China. Email: [email protected]
Downloaded from tdo.sagepub.com at University of British Columbia Library on July 28, 2015
XML Template (2015) [7.4.2015–5:53pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/TDOJ/Vol00000/150018/APPFile/SG-TDOJ150018.3d
(TDO)
[1–5] [PREPRINTER stage]
2
Tropical Doctor 0(0)
thrombocytopenia and increased hepatic enzymes.9 Clinically, the diagnosis of HGA may be difficult as non-specific symptoms, such as nausea, abdominal pain, diarrhoea and cough, proliferate. The combination of high fever and thrombocytopenia is found in several other diagnoses, including dengue, leptospirosis and haemorrhagic fever. It is suggested that HGA may be a major cause of unexplained fever during the tick season.10 However, it is rarely considered a possible pathogen in clinical practice, and its testing is not listed for routine diagnostic assessment. Thus, the actual number of cases may be considerably underestimated. Misdiagnosis and delayed antibiotic therapy will result in progressive deterioration of the patients. In China, mortality for HGA is much higher than that observed in the USA and Europe.11,12 The estimated HGA case fatality rate is believed to be low in China (range, 0.5–1%); but infection may be severe in the elderly or those immunocompromised.13 Active antibiotic therapy is advocated for all patients with confirmed HGA. Therefore, aetiology analyses are important, especially as HGA testing is not included in routine laboratory detection. In China, A. phagocytophilum is transmitted by the tick, Ixodes persulcatus.14 A history of prior tick bite is therefore an important clue, but most do not recall being bitten.15,16 Recently, nosocomial transmission has been documented through blood transfusion respiratory secretions.5,17 In our study, among sera of 133 patients with fever and thrombocytopenia, we found 30 infected by HGA.
Patients From March 2009 to September 2011, 133 patients with fever (>38.0 C) and thrombocytopenia (platelet counts
