Sero-Molecular Epidemiology of Japanese Encephalitis in Zhejiang, an Eastern Province of China.

BACKGROUND: Sporadic Japanese encephalitis (JE) cases still have been reported in Zhejiang Province in recent years, and concerns about vaccine cross-protection and population-level immunity have been raised off and on within the public health sphere. Genotype I (GI) has replaced GIII as the dominant genotype in Asian countries during the past few decades, which caused considerable concerns about the potential change of epidemiology characteristics and the vaccine effectiveness. The aim of this study was to investigate the prevalence of JE neutralizing antibody and its waning antibody trend after live attenuated JE vaccine immunization. Additionally, this study analyzed the molecular characteristics of the E gene of Zhejiang Japanese encephalitis virus (JEV) strains, and established genetic relationships with other JEV strains. METHODOLOGY/PRINCIPAL FINDINGS: A total of 570 serum specimens were sampled from community population aged from 0 to 92 years old in Xianju county of Zhejiang Province in 2013-2014. Microseroneutralization test results were analyzed to estimate the population immunity and to observe antibody dynamics in vaccinated children. E genes of 28 JEV strains isolated in Zhejiang Province were sequenced for phylogenetic tree construction and molecular characteristics analysis with other selected strains. Positive JE neutralizing antibody rates were higher in residents ≥35 years old (81%~98%) and lower in residents <35 years old (0~57%). 7 or 8 years after the 2nd live attenuated vaccine dose, the antibodies against for 4 different strains with microseroneutralization test were decreased by 55%~73% on seropositive rates and by 25%~38% on GMTs respectively. JEV strains isolated in recent years were all grouped into GI, while those isolated in the 1980s belonged to GIII. On important amino acid sites related to antigenicity, there was no divergence between the Zhejiang JE virus strains and the vaccine strain (SA14-14-2). CONCLUSION/SIGNIFICANCES: JE neutralizing antibody positive rates increase in age ≥10 years old population, likely reflecting natural infection or natural boosting of immunity through exposure to wild virus. JE seropositivity rates were quite low in <35 years old age groups in Zhejiang Province. Waning of neutralizing antibody after live attenuated vaccine immunization was observed, but the clinical significance should be further investigated. Both the peripheral antibody response and genetic characterization indicate that current live attenuated JE vaccine conferred equal neutralizing potency against GI or GIII of wild strains. GI has replaced GIII as the dominant genotype in Zhejiang in the past few decades. Although the chance of exposure to wild JE virus has reduced, the virus still circulates in nature; therefore, it is necessary to implement immunization program for children continually and to conduct surveillance activity periodically.

A hospital-associated measles outbreak among individuals not targeted for vaccination in eastern China, 2014.

BACKGROUND: An outbreak of measles occurred in early 2014 among individuals not targeted for vaccination-adults, and infants too young to vaccinate, in Xiangshan County, Zhejiang Province, in eastern China. OBJECTIVE: We conducted an investigation to identify risk factors responsible for this outbreak and to provide evidence-based recommendations for measles elimination strategies in China. METHODS: Measles was diagnosed using national standard case definitions. In a case-control study, 20 randomly selected measles patients were matched with controls selected from the same village or community as each case in a 1:2 case-to-control ratio. Controls were matched on age, within 5 years, and gender. We compared exposure histories during the 7-21 days before rash onset of the case and the same time period for the matched controls. We also conducted a measles antibody seroprevalence survey of a convenient sample of residual serum obtained from healthy patients during routine care in a hospital. RESULTS: The outbreak consisted of 45 measles cases, with an attack rate of 8.9/100,000 total population. Among cases, 91.1% (41/45) were adults (ranged 23-51 years) who had unknown vaccination histories; the other cases were infants younger than 8 months of age. The case-control study showed major risk factors to be a visit to Hospital X (OR(MH)=7.3, 95% CI: 1.8-30.7) and treatment in an IV room in Hospital X (OR(MH)=11.0, 95% CI: 1.3-96.1). The seroprevalence survey showed that 88.8% of adults had measles IgG antibodies, and that 100% of children 2-19 years of age were seropositive. CONCLUSIONS: The outbreak was primarily among age groups not targeted for vaccination-primarily adults, but with some children too young to vaccinate. Visiting a hospital was the major risk factor for measles transmission. We conclude that in addition to maintaining high 2-dose coverage with measles vaccine, working with hospital infection control programs to implement evidence-based strategies to prevent or limit hospital transmission is an important action for eliminating measles in eastern China.

[Relationship of Chinese medicine syndrome pattern with heart function and brain natriuretic peptide in patients with heart failure].

OBJECTIVE: To observe the relationship of Chinese medicine (CM) syndrome pattern with heart function detected by ultrasonic cardiography and brain natriuretic peptide (BNP) level in patients with heart failure (HF). METHODS: One hundred and sixteen inpatients of HF hospitalized in Dongfang Hospital from January, 2007 to January, 2009 were assigned to three groups according to their CM syndrome pattern differentiated, the qi-yin deficiency group (QYD), the qi-deficiency and blood-stasis group (QDBS) and the yang-deficiency with water overflowing group (YDWO). Ultrasonic cardiographic (USCG) parameters, including left ventricular end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were detected, and blood level of BNP was measured. RESULTS: LVEF was decreased while BNP was increased in patients with syndrome patterns in the order of QYD --> QDBS --> YDWO, and showed significant difference between groups (P < 0.01); CM syndrome patterns was related with all the USCG parameters and BNP level, especially the BNP (r = 0.71, P < 0.05) and LVEF (r = -0.34, P < 0.05). CONCLUSION: LVEF and BNP can reflect the severity of heart failure, and they could be taken as the beneficial objective and quantitative indices for syndrome pattern differentiation.

[Community-based study on disease burden of diarrhea in Zhejiang province].

OBJECTIVE: To study the status on economic burden of diarrhea in Zhejiang province so as to provide evidence for allocation of health resource as well as decision-making on health issues. METHODS: Multi-phases stratified random cluster sampling was used to select samples in the population. Data was collected on the incidence of diarrhea in the last two weeks as well as on the related cost due to medical care etc. RESULTS: The overall incidence (person per year) of diarrhea was 0.26, with 0.29 in the rural and 0.22 in the urban areas respectively. The incidence of diarrhea in children less than 5 was 0.66 (person per year), higher than in any of the age groups. The average direct cost of medical treatment was 69.23 Yuan with average direct cost of non-medical care was 8.29 Yuan for every person, while the indirect cost was 48.43 Yuan. In conclusion, the average disease burden of diarrhea in the province was 1.697 billion Yuan per year, which accounted for 1 per thousand of the GDP, with 1.217 billion Yuan in rural area and 0.480 billion Yuan in the urban areas respectively. The direct cost of medical care was 0.886 billion Yuan (52.21%) and the direct cost due to non-medical care was 0.124 billion Yuan (7.31%). The indirect cost appeared to be 0.480 billion Yuan (40.48%). Factors that affecting the cost would relate to: severity of diarrhea, medical insurance, location of residential area, age and education background of the patients, etc. CONCLUSION: Programs on diarrhea prevention and control should be strengthened to reduce the economic burden caused by this disease while special attention should be paid to those children who are under 5 years of age and living in the rural areas.

Infectivity of severe acute respiratory syndrome during its incubation period.

OBJECTIVE: To evaluate the infectivity of severe acute respiratory syndrome (SARS) during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to providing scientific evidence for updating protocols of medical isolation. METHODS: Individuals related with the two SARS chains of transmission in Beijing in 2003 and a group of individuals isolated for medical observation in Haidian district of Beijing during the SARS outbreak were selected as subjects of study. Contactors with SARS patients and those with symptom development following the contacts were investigated via questionnaire. Serum samples were collected from super transmitters and tested for SARS-CoV antibody by neutralization test and enzyme linked immunosorbent assay (ELISA). RESULTS: A total of 1112 contactors were investigated in three surveys. Of them, 669 had a history of close contact with symptomatic SARS patients, 101 developed symptoms with a rate of 15.1%, 363 had a history of close contact with patients in their incubation period, none of whom developed symptoms (0%). Serum samples were collected from 32 highly-exposed individuals, of whom 13 developing SARS symptoms after contact had serum samples positive for SARS-CoV antibody. Samples collected from the asymptomatic contactors were all negative for SARS-CoV antibody. CONCLUSION: SARS cases are infectious only during their symptomatic period and are non-infectious during the incubation period. Isolation for medical observation should be placed for individuals who are in close contact with symptomatic SARS patients. The results of our study are of decisive significance for the Ministry of Health to the definition of SARS close contactor.

A newly discovered Anaplasma phagocytophilum variant in rodents from southeastern China.

Anaplasma phagocytophilum was detected by polymerase chain reaction in 13 (14.1%) of 92 rodents captured from a mountainous area of Zhejiang Province in southeastern China. The nucleotide sequences of 1442-bp, nearly entire 16S rRNA gene amplified from these rodents, had 100% identity, but varied from all known corresponding sequences of A. phagocytophilum deposited in GenBank. To further identify and classify the variant, fragments of 357-bp partial citrate synthase gene (gltA), 849-bp major surface protein 4 gene (msp4), and 443-bp groESL heat-shock operon gene, were amplified and analyzed. The nucleotide sequences of the partial gltA gene amplified from the rodents were identical to each other, but distinct from previously reported A. phagocytophilum sequences,as were msp4 and groESL. These findings indicate that the newly discovered agent represents a novel A. phagocytophilum variant.

[A three-year follow-up study on sera specific antibody in severe acute respiratory syndrome cases after the onset of illness].

OBJECTIVE: To study the variation of specific antibody among convalescent of severe acute respiratory syndrome (SARS) patients through a three-year program. METHODS: Sera samples were collected from SARS cases in the 5th, 20th and 35th month after onset of the illness. The SARS-CoV specific antibody was detected for all of them by ELISA and neutralized test simultaneously. The titer of neutralizing antibodies was calculated using Reed-Muench method, and the comparison between different time groups was analyzed regarding the variance of data on repeated measures after logarithm conversion. RESULTS: 13, 17 and 13 sera samples were collected in the 5th, 20th and 35th month after onset. Results showed that despite the fact that the positive rates of ELISA antibody were 100%, 82.4% and 84.6% respectively,the neutralizing antibody was still positive for all the samples. The average neutralizing antibody titers were 1:43 (1:16-1:203), 1:36 (1:17-1:59) and 1:21 (1:10-1:39) on the 5th, 20th and 35th month after onset, and the differences were statistically significant (F = 60.419, P < 0.001). On the 35th month after the onset, 30.8% (4/13) of the patients were still having the neutralizing antibody level of above 1:36, but the neutralizing antibody level in another 30.8% (4/13) of the patients had decreased to as low as 1:10, when the cut-off level was set as 1:8. CONCLUSION: Results of the study indicated that the neutralizing antibody of SARS cases could last for at least three years, but the sera specific antibody in SARS cases decreased gradually when time went by. However, neutralizing antibody in some of the cases decreased to a lower level on the 35th month. Further follow-up study was worthwhile to observe the long-lasting profile of antibody existence on SARS cases.

Report and analysis of a scarlet fever outbreak among adults through food-borne transmission in China.

BACKGROUND: Scarlet fever is caused by group A beta-hemolytic streptococci (GAS). The clinical syndrome has receded in recent years, but occasionally explosive outbreaks do occur likely due to the emergence of GAS with virulence factors peculiar to this syndrome. METHODS: Following the notification of an unexpectedly large number of scarlet fever cases amongst adults associated with a school in Ningbo, China, in June 2006, the epidemiological and clinical features of the outbreak were investigated. Logistic regression was conducted to investigate the risk factors of the outbreak and its transmission route. RESULTS: Forty five individuals suffered scarlet fever with an attack rate of 4.98% (45/904). There was a single peak in the epidemic curve, with the majority of the cases occurring during the first two days of the outbreak. The median age of cases was 35.5 years (range 17-65). Most patients had fever (43/45), sore throat (40/45), scarlatinoid rash (39/45) and strawberry-like tongue (30/45). In laboratory detection, 45 cases' throat swabs samples were collected and GAS were isolated from 8 throat swabs samples. All of the cases, except for 2, had eaten the Plain Boiled Chicken (PBC) for lunch on June 6th, and teaching staff and students who had not eaten the PBC were not affected by the epidemic. Logistic regression analysis indicated that PBC was a key risk factor (OR=21.0, P<0.05). The chef of the school refectory was responsible for washing, braising, cutting, and distributing the PBC, and was identified as the likely source. CONCLUSIONS: We describe an outbreak of scarlet fever caused by GAS-contaminated food.

[Investigation on vibrio cholera carried in aquatic products of littoral areas, Zhejiang Province].

OBJECTIVE: To examine vibrio cholera (V.C) in aquatic products of littoral area, Zhejiang Province and to provide scientific evidence for administration of aquatic products and cholera epidemic control. METHODS: All 990 samples of aquatic products collected from local markets, eateries and aquafarms in three chosen areas. Samples were proliferated in alkaline liquid medium, and purified in NO: 4 medium, the isolations were identified biochemically, and phenotype of strains were defined by phagocyte and coagulation with V.C. diagnostic serum. Three virulence genes (ctx, ace, zct) of the isolated strains were detected by polymerase chain reaction (PCR). RESULTS: There were 1.41% samples caught by V.C., having a carrying rate highest in turtles of 8.9%. 14 strains were defined as three serogroups, and the numbers of Inaba, Ogawa, and Hikojima types were 2, 2, 10 respectively. Virulence genes had detected in 9 of 12 stains. All genes were detected in 5 strains, only ZOT genes in 3 strains, and both CTX and ACE genes in 1 strain. CONCLUSIONS: Aquatic products from inshore in Zhejiang Province caught with V.C. strains might be divided into three serogroups. Most of them should be virulence genes. Cholera epidemic outbreak might be caused by those contaminated products.

[Serological investigation on close contacts to patients with severe acute respiratory syndrome in an SARS outbreak].

OBJECTIVE: To study the evidence of severe acute respiratory syndrome (SARS) infection among close contacts to SARS patients and the level of sera IgG antibody in SARS cases. METHODS: Specific IgG antibody against SARS-CoV in serum samples from contacts to patients, five months before an SARS outbreak in Beijing. Neutralized test, ELISA and immunity adherence test were studied. Samples were collected after clinical onset of patients or close contacts to patients, for 22 - 24 weeks. 19 close contacts and 13 cases were included in the study. RESULTS: In close contacts, all tests were negative on three methods. All SARS cases were positive except one by immunity adherence test. The neutralized antibody levels were from 1:16 to 1:203, with medium level of 1:43. CONCLUSION: According to our survey, there was no latent infection among close contacts. IgG antibody in sera continued to be at higher levels among SARS cases 22 - 24 weeks after onset.

[Analyses on one case of severe acute respiratory syndrome 'super transmitter' and chain of transmission].

OBJECTIVES: To investigate the transmission process of severe acute respiratory syndrome (SARS) and to evaluate the infectiveness of SARS patients in different periods of disease epidemics. METHODS: Standardized questionnaire was used to conduct case investigation and contact tracing by combining the field investigation and telephone interview. Transmission process, infectivity, transmission chain and contact history of SARS were studied through data analyses. RESULTS: On 25th March 2003, a 91 year old man was admitted to Hospital J in Beijing with stroke and fever. He died on 30th March. From 31st March, there was an outbreak of SARS among his contacts in the family and in the hospital he was admitted to. Contacts would include his relatives, other co-patients and health care workers in the Hospital J. Chinese Field Epidemiology Training Program trainees conducted an investigation of the outbreak. Among the 207 contacts of the index cases through different generations, there were 36 cases of SARS (attack rate 17%) patients with one death. There were 12 cases having directly contact with the index case and 13 cases with one secondary case. The transmission chains of this outbreak could clearly be depicted. All the cases had close contacts during the symptomatic period of their index patients. Among the relatives, 85% of the cases had 3 - 5-day contact with their index patients after the onset of the illnesses. There was no significant difference between the two attack rates-70% for whose who had contact with the patient before and after illness onset) and 67% for those who only had contact after the onset of the illness. Out of the 44 social acquaintances and 38 of the family members who had contacts with the index patients during the incubation period, no one was found ill. Among the close contacts at the hospital who had no protection when providing care to the patient, the attack rate was found over 80%. CONCLUSIONS: All the secondary cases of this outbreak had a history of direct and close contacts to the index patients after the onset of the illness. There was no evidence indicating that SARS cases were infectious during their incubation period.

[Rapid assessment of safety injection in one county, north rural area in China].

OBJECTIVE: To estimate the frequency of injections and proportion of unsafe injections and to analyses the critical determinants of poor injection practices in general population in China. Also, to study knowledge, attitudes, practice research in providers and general population. METHODS: A random sample consisting residents and health care providers in a rural county was elected and interview about the frequency of received injection, as well as knowledge, attitudes and practices regarding injections were studied. RESULTS: Overall, 1 004 village residents, and 94 providers were interviewed. Among residents, 145 persons (14.4%), with 457 times (0.46 times per person) had received at least one injection during the previous 3 months. The frequency of injection was 1.84 per year. The proportion of received injections on treatment and immunizations was significantly different among > 12 years age group and < or = 12 years age group. Ninety-four point four percent of disposable syringes/needles were used for injections. Knowledge among the population and providers regarding injection safety was limited. CONCLUSION: Injections were moderately frequent in this rural area and the proportions of disposable syringes/needles used for injections was very high. Knowledge of safe injection and reasonable injection as well as consciousness of self-protection in the providers and residents need to be improved.