Shelan Liu

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.

Relationship Between Domestic and Wild Birds in Live Poultry Market and a Novel Human H7N9 Virus in China

To trace the source of the avian H7N9 viruses, we collected 99 samples from 4 live poultry markets and the family farms of 3 patients in Hangzhou city of Zhejiang province, China. We found that almost all positive samples came from chickens and ducks in live poultry markets. These results strongly suggest that the live poultry markets are the major source of recent human infections with H7N9 in Hangzhou city, Zhejiang province of China. Therefore, control measures are needed, not only in the domestic bird population, but also in the live poultry markets to reduce human H7N9 infection risk.

Comparative epidemiology and virology of fatal and nonfatal cases of hand, foot and mouth disease in mainland China from 2008 to 2014.

This study aimed to analyze the epidemiology and virology of fatal and nonfatal hand, foot, and mouth disease (HFMD) cases in Mainland China. A total of 10 714 237 survivors and 3046 deaths were reported from 2008 to 2014 June, with a case fatality rate of 0.03%. The morbidity of the survivors increased from 37.6/100 000 in 2008 to 139.6/100 000 in 2013 and peaked in 2012 at 166.8/100 000. However, the mortality varied around 0.03–0.04/100 000 across the time. Most of the survivors were distributed in the southern and eastern China, predominantly in the Guangxi and Hainan Province, whereas deaths were dominant in southern (Guangxi) and southwestern (Guizhou) China. The two groups showed similar seasonal fluctuations from 2008 to 2014, peaking in spring and early summer. Of the total cases, 93.97% were children less than 5 years of age, with those ≤ 2 years old accounting for 60.08% versus 84.02% in the survivor and death groups, respectively. Boys were at higher risk of infection than girls in both groups. Five years of virological surveillance showed that 43.73%, 22.04%, and 34.22% of HFMD cases were due to EV71, CoxA16 and other enteroviruses, respectively. EV71 was encountered in most deaths, with no substantial effect of age, gender, month, and year on incidence. Subgenotype C4a was the prevalent EV71 strain in Mainland China, with no significant difference in the VP1 gene related to virulence between the two groups. In conclusion, based on the largest population study, fatal and nonfatal HFMD cases, mainly caused by C4a of EV71, are circulating in Mainland China with a low‐cause fatality rate. Copyright

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.

Pandemic influenza A(H1N1) 2009 virus in pregnancy

Two hundred fourteen abstracts and 87 full texts regarding pregnant women infected with pandemic influenza A(H1N1) 2009 virus were systematically reviewed by using a PubMed search and assessing pandemic, clinical, laboratory test, vaccine, and control experiences. Both policy and health education were excluded. This review counted the total number of pregnant cases from different countries and analyzed their epidemic features, including trimester distribution, morbidity, hospitalization, intensive care unit admissions, maternal mortality, underlying diseases, complications, high‐risk factors for death, pregnancy outcome, and clinical symptoms compared with the previous pandemic seasonal influenza A/H1N1 as compared with the general population. Early identification and treatment were the most important factors in different countries and areas examined. The vaccine and antiviral drugs that have been the most efficient means to control the novel virus appear to be safe but require more extensive study. In the future, the focus should be placed on understanding vertical transmission and the severe mechanisms. Copyright

Epidemiology of human infections with avian influenza A(H7N9) virus in the two waves before and after October 2013 in Zhejiang province, China

We compared the epidemiological and clinical features of avian influenza A(H7N9) virus infections in the population in Zhejiang province, China, between March and April 2013 (first wave) and October 2013 and February 2014 (second wave). No statistical difference was found for age, sex, occupation, presence of underlying conditions, exposure history, white blood cell count, lymphocyte percentage and illness timeline and duration (all P > 0.05). The virus spread to 30 new counties compared to the first wave. The case-fatality rate was 22% in the first wave and 42% in the second (P = 0.023). Of those infected, 66% in the first wave and 62% in the second wave had underlying conditions. The proportion of those exposed to live poultry markets were 80% and 66%, respectively. We recommend permanent closure of live poultry markets and reformation of poultry supply and sales.

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.

Surveillance of Avian H7N9 Virus in Various Environments of Zhejiang Province, China before and after Live Poultry Markets Were Closed in 2013-2014.

Background To date, there have been a total of 637 laboratory-confirmed cases of human infection with avian influenza A (H7N9) virus across mainland China, with 28% (179/637) of these reported in Zhejiang Province. Surveillance of avian H7N9 virus was conducted to investigate environmental contamination during H7N9 outbreaks. We sought to evaluate the prevalence of H7N9 in the environment, and the effects of poultry market closures on the incidence of human H7N9 cases. Methods We collected 6740 environmental samples from 751 sampling sites across 11 cities of Zhejiang Province (China) between January 2013 and March 2014. The presence of H7N9 was determined by reverse transcription polymerase chain reaction, with prevalence compared between sites and over time. The relationship between environmental contamination and human cases of H7N9 infection were analyzed using Spearman’s ranked correlation coefficient. Results Of the 6740 samples, 10.09% (680/6740) were H7N9-positive. The virus was found to circulate seasonally, and peaked during the spring and winter of 2013–2014. The prevalence of the virus decreased from the north to the southeast of the province, coinciding with the geographical distribution of human H7N9 cases. Compared with other sampling sites, live poultry markets (LPMs) had the highest prevalence of H7N9 virus at 13.94% (667/4784). Of the various sample types analyzed, virus prevalence was highest for chopping board swabs at 15.49% (110/710). The prevalence of the virus in the environment positively correlated with the incidence of human H7N9 cases (r2 = 0.498; P < 0.01). Cities with a higher incidence of human H7N9 cases also had a higher prevalence of H7N9 among samples and at sampling sites. Following the closure of LPMs at the end of January 2014, the prevalence of H7N9 decreased from 19.18% (487/2539) to 6.92% (79/1141). This corresponded with a decrease in the number of human H7N9 cases reported. Conclusions The prevalence of H7N9 virus in environmental samples oscillated seasonally, regardless of whether LPMs were open. The presence of H7N9 in environmental samples positively correlated with the number of human H7N9 cases, indicating that eradication of the virus from the environment is essential in reducing the numbers of H7N9 cases and halting the spread of the virus.

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.

Patterns of polymorphism and divergence in the VP1 gene of enterovirus 71 circulating in the Asia-Pacific region between 1994 and 2013

Enterovirus 71 has been implicated in several outbreaks of hand, foot and mouth disease in the Asia-Pacific region. The present study aimed to achieve comprehensive evolutionary dynamic aspects of EV71 during 1994-2013, based on phylogenetic analyses of the VP1 sequences. The results indicated that 4 genotypes, namely C4, C1, C2 and B4 are the predominant strains, especially in Southeast Asian countries. No common ancestor was shared in different countries. Fourteen sites of substitutions were detected in the VP1 gene sequences; including the most common sites related to neutralization at position V249I [47.1% (189/401)] and A289T [42.6% (171/401)]. However, the sites Q22H and Q22R associated with increased virulence were recognized only in 13.7% (55/401) and 18% (72/401), respectively. None of the above mutations seemed to become fixed because the ratio of Ka/Ks was greater than 1.0. Mutations K43E, A58T, S184T, and T240S could possibly change the spatial structure. Two mutations, G145E and T240S, could obviously affect the hydrophobicity of VP1 and thus alter the EV71 immunoreactivity. In conclusion, the VP1 gene of EV71 strains circulating in the Asia-Pacific region during 1994-2013, showed polymorphisms and divergence with very slow evolution rate, which may be one of the reasons for periodic outbreaks in this area.