Molecular epidemiology of hepatitis B virus genotypes and subgenotypes in ethnic minority populations, Yunnan province, China.

The aim of our study was to determine the distribution of hepatitis B virus (HBV) genotypes and subgenotypes in ethnic minorities in Yunnan province to provide evidence supporting the theoretical basis for hepatitis B prevention and control. We obtained serum samples and demographic data from 765 individuals reported by Yunnan province who had either acute or chronic HBV infection and were from one of 20 ethnic minority populations: Achang, Bai, Brown, Tibetan, Dai, Deang, Dulong, Hani, Hui, Jingpo, Lahu, Yi, Lisu Miao, Naxi, Nu, Pumi, Wa, Yao, or Zhuang people. We sequenced the HBV DNA and determined the genotypes and subgenotypes of the isolated HBVs. We mapped the genotype and subgenotype distribution by ethnic minority population and conducted descriptive analyses. There were four genotypes among the 20 ethnic groups: genotype B (21.3% of samples), C (76.6%), D (1.8%) and I (0.3%). The most common subgenotype was C1. There were no genotype differences by gender (P = 0.954) or age (P = 0.274), but there were differences by region (P < 0.001). There were differences in genotype distribution (P < 0.001) and subgenotype distribution (P = 0.011) by ethnic group. Genotype D was most prominent in Tibet and most HBV isolates were C/D recombinant viruses. The only two genotype I virus isolates were in Zhuang people. Susceptibility and geographic patterns may influence HBV prevalence in different ethnic populations, but additional research is needed for such a determination.

Health and economic costs of an import-initiated measles outbreak in an international border area of Yunnan Province.

BACKGROUND: Measles outbreaks often require labor- and resource-intense response. A border-area measles outbreak occurred in Yunnan province that required outbreak response immunization for its containment. We report results of our investigation into the outbreak and the health sector costs of the response activities, with the goal of providing evidence for policy makers when considering the full value of vaccines and of measles elimination. METHODS: We conducted case investigations to determine sources of infection and routes of transmission. Costs of outbreak response activities incurred by health sector were determined through retrospective interviews and record reviews of staff. RESULTS: In total, 67 measles cases were confirmed, including 4 cases imported from Myanmar. Among the 33 cases aged between 8 months and 14 y old, 22 (66∙7%) had received 2 doses of MCV; 2 (6∙0%) had received 1 dose of MCV; 9 (27∙3%) had not received MCV. The first 4 cases had been infected in Myanmar, and we identified 8 transmission clusters with a total of 62 cases. Transmission among Yunnan province residents occurred in schools, family settings, and at gatherings. The overall cost to control the outbreak was $214,774, for a per-case cost of $3,206. The outbreak response vaccination campaign accounted for 64% of the total outbreak costs. CONCLUSIONS: Despite high population immunity among Yunnan province children and adolescents, an import-related measles outbreak occurred among individuals who were not vaccinated or had vaccine failure in the across-border area. The economic cost of the outbreak was substantial. Investment in a sensitive measles surveillance system to detect outbreaks in a timely manner, maintaining high population immunity to measles, and reinforcing cross-border collaboration with neighboring countries support achieving and sustaining measles elimination in the border areas of China.

Measles immunity in the China-Myanmar border region, Lincang city, Yunnan province, 2017.

Background: A recent measles importation-related outbreak in the China-Myanmar border region required outbreak response immunization to stop the outbreak, raising the question of measles immunity in the area. We conducted two measles serological surveys to develop a seroepidemiological profile of native Chinese citizens and registered Myanmar immigrants to identify strategies to promote measles elimination in the border region.Methods: We conducted a clinic-based measles serosurvey of Myanmar registered immigrants (n = 300) and a population-based serosurvey of Chinese Lincang residents (n = 355). Serum samples were tested with enzyme-linked immunosorbent assays to assess immunity to measles.Results: We found that Myanmar immigrants had a seropositivity rate of 85.3% (95% CI: 81.3-89.4) with a GMT of 924.9 mIU/ml, and Lincang Chinese nationals had a seropositivity rate of 94.6% (95% CI:92.3-97.0) with a GMT of 1363.3 mIU/ml. Myanmar children 2-6 years of age and 7-14 years of age were more likely to be susceptible to measles than same-aged Chinese children: odds ratios 23.00 (95% CI: 5.10-103.69, P < .001) and 7.95 (95% CI: 1.66-38.01,P = .009), respectively.Conclusions: We recommend conducting a catch-up vaccination program for Myanmar children ≤15 years old.

Reduction patterns of Japanese encephalitis incidence following vaccine introduction into long-term expanded program on immunization in Yunnan Province, China.

BACKGROUND: Japanese encephalitis (JE) is a leading cause of childhood viral encephalitis both at global level and in China. Vaccination is recommended as a key strategy to control JE. In China most JE cases have been reported in southwest provinces, which include Yunnan. In this study, we quantify the epidemiological shift of JE in Yunnan Province from 2005 to 2017, covering before and after the introduction of JE vaccination into routine Expanded Program on Immunization (EPI) in 2007. METHODS: We used routinely collected data in the case-based JE surveillance system from 2005 through 2017 in Yunnan. Cases were reported from hospital and county-level Centers for Disease Control in line with the National JE Surveillance Guideline. Epidemiological data were extracted, analysed and presented in appropriate ways. Immunization coverage was estimated from actual JE doses administered and new births for each year. RESULTS: A total 4780 JE cases (3077 laboratory-confirmed, 1266 clinical and 437 suspected) were reported in the study period. Incidence of JE (per 100 000 population) increased from 0.95 in 2005 to 1.69 in 2007. With increase in vaccination coverage, incidence rates decreased steadily from 1.16 in 2009 to 0.17 in 2017. However, seasonality remained similar across the years, peaking in June-September. Banna (bordering Myanmar and Laos), Dehong (bordering Myanmar), and Zhaotong (an inland prefecture) had the highest incidence rates of 2.3, 1.9, and 1.6, respectively. 97% of all cases were among local residents. As vaccination coverage increased (and incidence decreased), proportion of JE cases among children < 10 years old decreased from 70% in 2005 to 32% in 2017, while that among adults ≥20 years old increased from 12 to 48%. There were a large number of JE cases with unknown treatment outcomes, especially in the earlier years of the surveillance system. CONCLUSIONS: The 13-year JE surveillance data in Yunnan Province showed dramatic decrease of total incidence and a shift from children to adults. Improving vaccination coverage, including access to adults at risk, and strengthening the JE surveillance system is needed to further control or eliminate JE in the province.

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population.

The host immune system plays a key role in the elimination of infected cells which depend on killer-cell immunoglobulin-like receptors (KIR), human leucocyte antigen (HLA) class I molecules and their combinations. To evaluate the roles of HLAclass I, KIR genes and their combination in Chronic hepatitis C virus (HCV) infection (CHC), a total of 301 CHCs and 239 controls in a Chinese Han population were included for HLA and KIR genotyping using next-generation sequencing and multiplex PCR sequence-specific priming, respectively. The allele frequency of HLA-C*08:01 was significantly higher in the CHCs than that of the controls (0.088 vs. 0.040, OR = 2.332, 95%CI: 1.361-3.996, p = 0.022), while the frequencies of B*13:01 (0.032 vs. 0.084, OR = 0.357, 95%CI: 0.204-0.625, p = 0.009) and C*08:04 (0.008 vs. 0.038, OR = 0.214, 95%CI: 0.079-0.581, p = 0.022) were significantly lower in the CHCs. The frequencies of haplotype A*11:01-C*08:01 were higher in the CHCs (0.058 vs. 0.019, OR = 3.096, 95%CI: 1.486-6.452, p = 0.026), while haplotype B*13:01-C*03:04 were lower in the CHCs compared to the controls (0.028 vs. 0.071, OR = 0.377, 95%CI: 0.207-0.685, p = 0.012). No association of CHC with KIR genes, genotypes, or haplotypes, as well as HLA/KIR combinations was observed. Our results indicated that HLA-C*08:01 was a risk factor for CHC, while HLA-C*08:04 and HLA-B*13:01 were protective factors against CHC. Haplotypes HLA-A*11:01-C*08:01 could increase susceptibility to CHC, while HLA-B*13:01-C*03:04 could be protective against CHC in the Chinese Han population.

Investigation of the risk factors associated with the failure of hepatitis B vaccination of neonates in Yunnan province, China.

OBJECTIVE: This study aimed to investigate HBsAg positive rates and risk factors of HBV infection among the children less than 15 years old in Yunnan province, a remote southwest part of mainland China. METHODS: Multi-stage sampling was used to randomly select study subjects from 9,360,000 individuals. Hepatitis B vaccine inoculation rate and HBsAg positive rate were investigated, and then propensity score and generalized linear mixed model (GLMMs) were applied to the case-control study. RESULTS: The average HBsAg positive rate was 1.81%, with 1.2% in urban areas and 2.4% in rural areas. Rate of first-dose-in-time in urban areas was 77.7%, obviously higher than 49.5% in rural areas (χ2=2811.71, P<0.01). Similarly, 3-dose completion coverage rate in urban areas was 93.7%, also higher than 79.0% in rural areas (χ2=1561.43, P<0.01). Maternal HBeAg positivity and HBsAg positivity were proved to be the main risk factors of children with HBV infection. Moreover, paternal HBeAg positivity, paternal HBsAg positivity, the absence and unknown status of HBV vaccine inoculation were risk factors of children with HBV infection as well. CONCLUSION: It was very important to improve the HBV vaccine inoculation rates. Delivering babies in hospital and timely inoculation with HBV vaccine were efficient ways to prevent HBV vertical transmission.

Measles outbreak prevention and control among adults: Lessons from an importation outbreak in Yunnan province, China, 2015.

BACKGROUND: The incidence of measles in Yunnan Province among vaccine target-age children has decreased markedly after attaining and sustaining high 2-dose coverage of measles containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs). Most cases of measles now occur among adults. In 2015, we investigated a measles outbreak among adults to determine transmission patterns and the potential role of nosocomial transmission. METHODS: We enhanced measles surveillance using retrospective active case search. We conducted case investigations to determine sources of infection and routes of transmission; laboratory testing included serologic and molecular diagnostic methods. RESULTS: Twenty-two outbreak-associated cases of measles were identified; most (86.36%) were among individuals 20 to 39 years of age (range, 7 months to 43 years). We interviewed 19 individuals who had acquired measles. The first 3 cases were infected in Tibet; 12 (63%) were hospital-acquired infections; 2 (11%) were community-acquired; and 2 (11%) were family-contact cases. We conducted outbreak response immunization (ORI) that provided MCV without regard to vaccination status; 10,596 residents between 20 and 40 years of age were vaccinated. A serological survey conducted during the ORI showed that 84% of the 20-40 year-olds were immune to measles prior to vaccination. Post-vaccination serological testing showed 100% were immune. CONCLUSIONS: Despite high population immunity among children and adolescents, imported measles virus transmission occurred among adults in a provincial cross-border area. Nosocomial transmission and measles immunity gaps among adults poses a threat to measles elimination and highlights the strategy of targeting adults during ORI to outbreaks with adult-to-adult transmission.

Risk factors related to the failure of prevention of hepatitis B virus Mother-to-Child transmission in Yunnan, China.

OBJECTIVE: To investigate the relationship between the failure of prevention of hepatitis B virus Mother-to-Child transmission and HBV serological pattern, viral load as well as HBV genotypes. METHODS: 2765 pairs of mother-infant matched samples were collected. These pregnant women were HBsAg positive and delivered at hospital from January 1st, 2011 to June 30th, 2011. Of these samples, 26 pairs of sera samples were randomly selected from 114 pairs of samples which failed in the prevention of hepatitis B virus Mother-to-Child transmission. Serological tests, viral load and genotype detection were performed for further analysis. Additionally, the selected subjects were followed and tested again in 2014. RESULTS: HBeAg positive rates were 76.92% and 69.23% in mother group and infant group respectively, showed no statistical difference. The average HBV DNA levels were >2×105IU/ml in both mother group and infant group. Genotype analysis revealed that 11 pairs of mother-infant matched samples belonged to C gene type and another 11 pairs were B gene type. Different genotypes were observed in 4 pairs of mother-infant matched samples. CONCLUSION: HbeAg positive and high HBV DNA level were two major risk factors of HBV mother to child transmission. Additionally, nosocomial infection was another potential way of HBV vertical transmission, especially in remote area of Yunnan province.

Assessment of HCV genotypes in Yunnan Province of Southwest China.

Recently, we reported that the frequency of hepatitis C virus (HCV) genotypes and subtypes has rapidly changed among intravenous drug users (IDUs) in Yunnan Province over the last 5 years; this is especially true for subtype 6a which has increased in frequency from 5 to 15%. Here, we assessed 120 HCV-positive plasma samples from the general population (GP). HCV NS5B fragments were amplified and sequenced by PCR. We identified four HCV genotypes (1, 2, 3 and 6) and seven HCV subtypes (1b, 2a, 3a, 3b, 6a, 6n, and 6k) in this population. Genotype 3 was predominant, with a distribution frequency of 0.484, followed by genotype 1 (0.283), genotype 6 (0.133) and genotype 2 (0.100). HCV subtypes 3b (frequency 0.292) and 1b (frequency 0.283) were the most common subtypes. A comparison of the current data with previous results reported for IDUs showed that the distribution frequencies of genotypes 1, 2 and 6 were significantly different between patients in the GP and IDUs (P < 0.05). Among the HCV subtypes, the distribution frequencies of 1b, 2a, 6a, and 6n were significantly different between patients in the GP and IDU groups (P < 0.05). Moreover, Phylogenetic analyses showed that HCV subtype 6a strains isolated from IDUs and the GP were intermixed and not separately clustered. HCV subtype 6a was predominant not only among IDUs but also among those in the GP in the Guangdong Province and Vietnam. However, HCV subtype 6a was predominant only among IDUs and not among those in the GP in the Yunnan and Guangxi Provinces. Our results indicate that the HCV subtype 6a could rapidly spread across China.

Complete Genome Analysis of an Enterovirus EV-B83 Isolated in China.

Enterovirus B83 (EV-B83) is a recently identified member of enterovirus species B. It is a rarely reported serotype and up to date, only the complete genome sequence of the prototype strain from the United States is available. In this study, we describe the complete genomic characterization of an EV-B83 strain 246/YN/CHN/08HC isolated from a healthy child living in border region of Yunnan Province, China in 2008. Compared with the prototype strain, it had 79.6% similarity in the complete genome and 78.9% similarity in the VP1 coding region, reflecting the great genetic divergence among them. VP1-coding region alignment revealed it had 77.2-91.3% with other EV-B83 sequences available in GenBank. Similarity plot analysis revealed it had higher identity with several other EV-B serotypes than the EV-B83 prototype strain in the P2 and P3 coding region, suggesting multiple recombination events might have occurred. The great genetic divergence with previously isolated strains and the extremely rare isolation suggest this serotype has circulated at a low epidemic strength for many years. This is the first report of complete genome of EV-B83 in China.

[Effect of resuscitation strategy based on the early goal directed therapy on the prognosis of patients with shock].

OBJECTIVE: To evaluate the effects of fluid management strategies in early goal directed therapy (EGDT) on the prognosis of patients with shock. METHODS: Clinical data of 79 patients with septic shock or hemorrhagic shock admitted to emergency intensive care unit (EICU) of the First People's Hospital of Yunnan Province were retrospectively analyzed. Patients were divided into continual fluid administrating group (n=41) in accordance with protocol calculating approximating fluid volume and adjust the infusion speed based on blood pressure, heart rate, pulse saturation of blood oxygen (SpO(2)) and urine output with the end of fluid resuscitation was set to restore spontaneous circulation function and wean off vasoactive drugs, and the conservative fluid resuscitation group (n=38) by means of using vasoactive agents to maintenance blood pressure after infusing amount (20 ml/kg) of liquid early, respectively. The 28-day mortality and the time of using pressure agents were compared between two groups. According to the 28-day mortality, patients were further divided into the survival group (n=37) and death group (n=42), and acute physiology and chronic health evaluation II (APACHEII) score was compared between two groups. Logistic regression analysis of prognostic factors was conducted to identify and describe the relationship between the prognosis and fluid resuscitation methods and strategies. RESULTS: The 28-day mortality of continual fluid administrating group was significantly lower than that of the conservative fluid resuscitation group (14.63% vs. 94.74%, P<0.01), total drugs supporting time (hours) was significantly shorter than that in conservative fluid resuscitation group (33.24±17.56 vs. 58.29±34.78, P<0.05). Thirty-six cases of 42 death patients received conservative fluid resuscitation (85.7%), but 35 cases of 37 survival patients received continual fluid administration (94.6%). Logistic regression analysis showed that odds ratio (OR) of brain natriuretic peptide before death or shifted out ICU was 0.9136, 95% confidence interval (95%CI) was 0.8125 to 0.9986, regression coefficient was -0.0931, P=0.0478, OR of procalcitonin before death or shifted out ICU was 0.9095, 95%CI was 0.8294 to 0.9973, regression coefficient was -0.0949, P=0.0436, and OR of blood lactate level before death or shifted out ICU was 0.5023, 95%CI was 0.2833 to 0.8905, regression coefficient was -0.6885, P=0.0184. CONCLUSIONS: Ongoing fluid resuscitation early in accordance with method to theoretically calculate fluid volume and to adjust infusion speed based on blood pressure, heart rate, SpO(2) and urine, withdrawal of vasoactive drugs, the mortality of patients with shock was significantly reduced.

Evaluation of hepatitis A surveillance data and outbreak detection in Yunnan Province, China, from 2004 through 2009.

Hepatitis A outbreaks may be averted if detected early. The current study objectives were to evaluate the quality and timeliness of hepatitis A surveillance data from Yunnan Province, China, and to evaluate the sensitivity of the system for reporting outbreaks. The study period was from January 1, 2004 through December 31, 2009. Records from the National Infectious Diseases Surveillance System (NIDSS) were compared with those from local hospitals. The timeliness of case detecting, reporting and updating was also analyzed. The numbers of cases in a specific location during a moving time interval were computed to identify past outbreaks which were then validated against reported cases. The NIDSS received 38,095 reports during the study period; of which 6% were duplicates, and 26% had serological confirmation. The sensitivity and positive predictive value of cases were 96% and 98%, respectively. Time from onset to diagnosis remained constant over the 6-year period. Delays in reporting became shorter, and quality control of data improved over the period, but the timeliness of identifying duplicate records did not. Based on data from NIDSS, 9 outbreaks should have been reported, but only 3 were reported. The 3 reported outbreaks were shorter in duration than the 6 unreported ones, but the numbers of cases involved were not significantly different. Surveillance data needs improvement in updating timeliness. The system for outbreak detection and reporting needs to be improved.