Huakun Lv

Systematic review of severe fever with thrombocytopenia syndrome: virology, epidemiology, and clinical characteristics.

Severe fever with thrombocytopenia syndrome (SFTS) was firstly discovered in China in 2010, followed by several reports from many other countries worldwide. SFTS virus (SFTSV) has been identified as the causative agent of the disease and has been recognized as a public health threat. This novel Bunyavirus belongs to the Phlebovirus genus in the family Bunyaviridae. This review also describes the different aspects of virology, pathogenesis, epidemiology, and clinical symptoms on the basis of the published article surveillance data and phylogenetic analyses of viral sequences of large, medium, and small segments retrieved from database using mega 5.05, simplot 3.5.1, network 4.611, and epi information system 3.5.3 software. SFTS presents with fever, thrombocytopenia, leukocytopenia, and considerable changes in several serum biomarkers. The disease has 10 ~ 15% mortality rate, commonly because of multiorgan dysfunction. SFTSV is mainly reported in the rural areas of Central and North‐Eastern China, with seasonal occurrence from May to September, mainly targeting those of ≥50 years of age. A wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs, and chickens have been proven seropositive for SFTSV. Ticks, especially Haemaphysalis longicornis, are suspected to be the potential vector, which have a broad animal host range in the world. More studies are needed to elucidate the vector–animal–human ecological cycle, the pathogenic mechanisms in high level animal models and vaccine development.

Epidemiological characteristics of severe fever with thrombocytopenia syndrome in Zhejiang Province, China

OBJECTIVES To summarize the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang Province, China. METHODS A standardized questionnaire was used to collect information on demographic features, exposure history, clinical symptoms, and timelines of medical visits. Descriptive statistics were used to analyze the characteristics of SFTS. RESULTS A total of 65 cases of SFTS were identified in Zhejiang Province from 2011 to 2013, of whom 34 were male and 31 were female. The median age was 66 years and 60 cases occurred in persons aged ≥ 50 years. The majority (91%) of SFTS cases occurred between May and August. With regard to exposure history, patients had pursued outdoor activities (63%), had a history of exposure to a tick (68%) or tick bite (29%), bred domestic animals (31%), or had a history of exposure to a mouse (57%), and some patients had a multi-exposure history. Approximately 98.46% of patients were hospitalized, and symptoms of the illness included fever (98%), fatigue (71%), chills (51%), etc. Two family clusters occurred, although there was no person-to-person transmission. CONCLUSIONS In Zhejiang Province, SFTS is prevalent between May and August among elderly persons who live in hilly areas, and clinical features are not specific. More emphasis should be given to this disease and further training of medical personnel should be carried out to prevent misdiagnosis.

DETECTION OF BARTONELLA SPECIES IN SMALL MAMMALS FROM ZHEJIANG PROVINCE, CHINA

To estimate the prevalence of Bartonella in small mammals of different species, during different seasons, and at different study sites, and to provide baseline data for the risk assessment of human Bartonella infection, we captured small mammals using snap traps in Zhejiang Province, China. Bartonella species were detected in small-mammal samples by polymerase chain reaction and positive amplicons were sequenced. Bartonella DNA was detected in 47% (90/192) of Apodemus agrarius, 31% (14/45) of Rattus losea, 16% (7/43) of Rattus norvegicus, 24% (9/37) of Eothenomys melanogaster, 4% (1/28) of Niviventer confucianus, 30% (7/23) of Suncus murinus, 22% (2/9) of Microtus fortis, 27% (2/7) of Rattus tanezumi, and 29% (2/7) of Apodemus peninsulae. No Bartonella DNA was detected in 27 unidentified Soricidae or nine Mus musculus. This is the first report of Bartonella DNA detected in E. melanogaster and N. confucianus. The prevalence of Bartonella DNA varied among small-mammal species, study sites, and seasons; the prevalence of Bartonella DNA between genders did not vary significantly within a species. The sequences we report were most similar to Bartonella grahamii.

The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report.

This study reports the first death caused by a novel avian influenza A (H7N9) virus in Zhejiang Province, China. The patient had chronic hepatitis B and history of exposure to poultry. The patient initially complained of diarrhea and influenza-like symptoms on March 7 and 14 respectively. The disease progressed to severe pneumonia, sustained hypoxia, and coagulation abnormalities. The patient died on March 27 because of respiratory failure, multiple organ failure, and disseminated intravascular coagulation without oseltamivir treatment. This H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai, Jiangsu, Anhui, etc. Analysis of hemagglutinin, neuramidinase, and matrix genes indicated that the isolates share the same avian origin, have low virulence, and are sensitive to oseltamivir, but are resistant to adamantine. Only the isolate that caused the fatality exhibited substitution of Q226I in the HA gene, which indicates a potentially enhanced human affinity. The secondary transmission rate was 1.6% (2/125). Only two health workers presented with influenza-like symptoms, and they subsequently tested negative for H7N9 RNA. In conclusion, underlying disease, late diagnosis, and untimely antiviral treatment are possible high-risk factors for infections and death caused by the lowpathogenicity avian influenza A (H7N9). Person-to-person transmission of the H7N9 virus was not detected among close contacts, but such transmission should be investigated in the future. Expanding and enhancing surveillance will help in the early discovery and diagnosis of suspected cases, which will reduce the number of severe cases and deaths.

Epidemiological Characteristics and Spatial-Temporal Clusters of Hand, Foot, and Mouth Disease in Zhejiang Province, China, 2008-2012.

Hand, foot and mouth disease (HFMD) is one of the major public health concerns in China. Being the province with high incidence rates of HFMD, the epidemiological features and the spatial-temporal patterns of Zhejiang Province were still unknown. The objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. The surveillance data of HFMD during 2008–2012 were collected from the communicable disease surveillance network system of Zhejiang Provincial Center for Disease Control and Prevention. The distributions of age, gender, occupation, season, region, pathogen’s serotype and disease severity were analyzed to describe the epidemiological features of HFMD in Zhejiang Province. Seroprevalence survey for human enterovirus 71 (EV71) in 549 healthy children of Zhejiang Province was also performed, as well as 27 seroprevalence publications between 1997 and 2015 were summarized. The spatial-temporal methods were performed to explore the clusters at county level. Furthermore, pathogens’ serotypes such as EV71 and coxsackievirus A16 (Cox A16) and meteorological factors were analyzed to explore the potential factors associated with the clusters. A total of 454,339 HFMD cases were reported in Zhejiang Province during 2008–2012, including 1688 (0.37%) severe cases. The annual average incidence rate was 172.98 per 100,000 (ranged from 72.61 to 270.04). The male-to-female ratio for mild cases was around 1.64:1, and up to 1.87:1 for severe cases. Of the total cases, children aged under three years old and under five years old accounted for almost 60% and 90%, respectively. Among all enteroviruses, the predominant serotype was EV71 (49.70%), followed by Cox A16 (26.05%) and other enteroviruses (24.24%) for mild cases. In severe cases, EV71 (82.85%) was the major causative agent. EV71 seroprevalence survey in healthy children confirmed that occult infection was common in children. Furthermore, literature summary for 26 seroprevalence studies during 1997–2015 confirmed that 0–5 years group showed lowest level of EV71 seroprevalence (29.1% on average) compared to the elder children (6–10 years group: 54.6%; 11–20 years group: 61.8%). Global positive spatial autocorrelation patterns (Moran’s Is>0.25, P<0.05) were discovered not only for mild cases but also for severe cases, and local positive spatial autocorrelation patterns were revealed for counties from the eastern coastal and southern regions. The retrospective space-time cluster analysis also confirmed these patterns. Risk factors analyses implied that more EV71 and less sunshine were associated with the clusters of HFMD in Zhejiang Province. Our study confirmed that Zhejiang Province was one of the highly epidemic provinces in China and that the epidemiological characteristics of HFMD were similar to other provinces. Occult infection in elder children and adults was one of the important reasons why most HFMD cases were children aged under-five. Combining the results of spatial autocorrelation analysis and the space-time cluster analysis, the major spatial-temporal clusters were from the eastern coastal and southern regions. The distribution of pathogens’ serotypes and the level of sunshine could be risk factors for, and serve as an early warning of, the outbreak of HFMD in Zhejiang Province.

Seroprevalence of severe fever with thrombocytopenia syndrome virus in southeastern China and analysis of risk factors.

SUMMARY Severe fever with thrombocytopenia syndrome virus (SFTSV) has been prevalent for some time in China and it was first identified in 2010. However, the seroprevalence of SFTSV in the general population in southeastern China and risk factors associated with the infection are currently unclear. Blood samples were collected from seven counties across Zhejiang province and tested for the presence of SFTSV-specific IgG antibodies by ELISA. A total of 1380 blood samples were collected of which 5·51% were seropositive for SFTSV with seroprevalence varying significantly between sites. Seroprevalence of SFTSV in people who were family members of the patient, lived in the same village as the patient, or lived in a different village than the patient varied significantly. There was significant difference in seroprevalence between participants who bred domestic animals and participants who did not. Domestic animals are probably potential reservoir hosts and contact with domestic animals may be a transmission route of SFTSV.

Antibodies against severe fever with Thrombocytopenia syndrome Virus in healthy persons, China, 2013

In June 2013, a subclinical infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Zhejiang Province, China, prompting seroprevalence studies in 6 districts within the province. Of 986 healthy persons tested, 71 had IgG antibodies against SFTSV. This finding suggests that most natural infections with SFTSV are mild or subclinical.

Novel and predominant pathogen responsible for the enterovirus-associated encephalitis in eastern China

Enteroviruses (EV) have been increasingly identified as the causative agent for unknown etiological encephalitis in many parts of the world, but the long period surveillance for enterovirus-associated encephalitis (EAE) was not reported in China. From 2002-2012 in Zhejiang, Coxsackieviruses A9, B1, B2, B3, B4, B5; and echoviruses 3, 4, 6, 9, 14, 25, 30 were detected from the unknown etiological encephalitis cases, with coxsackievirus B4 been identified here for the first time. From 2002-2004 and 2010-2012, echovirus 30 was found to be the periodically predominant serotype for in the EAE. The molecular typing results showed that all the EV isolates from this study belonged to the human EV B (HEV B) family and were distributed in three clusters.

Comparison of Characteristics between Patients with H7N9 Living in Rural and Urban Areas of Zhejiang Province, China: A Preliminary Report

A total of 134 cases of H7N9 influenza infection were identified in 12 provinces of China between March 25 and September 31, 2013. Of these, 46 cases occurred in Zhejiang Province. We carried out a preliminary comparison of characteristics between rural and urban H7N9 cases from Zhejiang Province, China. Field investigations were conducted for each confirmed H7N9 case. A standardized questionnaire was used to collect information about demographics, exposure history, clinical signs and symptoms, timelines of medical visits and care after onset of illness. Of the 46 H7N9 cases in Zhejiang Province identified between March 25 and September 31, 2013, there were 16 rural cases and 30 urban cases. Compared to urban cases, there was a higher proportion of females among the rural cases [11/16 (69%) vs. 6/30 (20%), P = 0.001]. Among the rural cases, 14/15 (93%) with available data had a history of recent poultry exposure, which was significantly higher than that among urban cases (64%, P = 0.038). More patients from the rural group had a history of breeding poultry compared with those from the urban group [38% (6/16) vs. 10% (3/30), respectively; P = 0.025]. Interestingly, the median number of medical visits of patients from rural areas was higher than that of patients from urban areas (P = 0.046). There was no difference between the two groups in terms of age distribution, fatality rate, incubation period, symptoms, and underlying medical conditions. In conclusion, compared to patients from urban areas, more patients from rural areas were female, had an exposure history, had a history of breeding poultry, and had a higher number of medical visits. These findings indicate that there are different exposure patterns between patients living in rural and urban areas and that more rural cases were infected through backyard poultry breeding.

Mild Illness in Avian Influenza A(H7N9) Virus–Infected Poultry Worker, Huzhou, China, April 2013

During April 2013 in China, mild respiratory symptoms developed in 1/61 workers who had culled influenza A(H7N9) virus–infected poultry. Laboratory testing confirmed A(H7N9) infection in the worker and showed that the virus persisted longer in sputum than pharyngeal swab samples. Pharyngeal swab samples from the other workers were negative for A(H7N9) virus.