Evaluating the population measles susceptibility in Tianjin, China.

BACKGROUND: Measles is a highly infectious illness requiring herd immunity of 95% to interrupt transmission. China has not reached elimination goals despite high vaccination coverage. We estimated the population susceptibility against measles in Tianjin, China and to tailor awareness raising activities in the measles elimination plan. METHODS: Age-specific measles seroprevalence was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA) on 12,164 individual aged 0-44 years in 2009-2018. Measles IgG avidity testing was performed to confirm the relationship of the waning immunity after vaccination and secondary vaccination failures (SVF) on 324 confirmed measles cases in 2013-2018. RESULTS: 11,108 samples (91.32%) tested positive for measles IgG, 239 (1.96%) tested as equivocal and 817 (6.72%) were negative. The age distribution of measles cases in Tianjin followed a U-shaped curve and was highest for those at <8 months and again at 20-39 years which correlated closely with the age distribution of measles susceptibility based on measles IgG antibody status (r = 0.72, P < 0.001). The seropositivity rate and antibody geometric mean concentration (GMC) for the 2018 study population were significantly lower (χ2 = 7.45, P = 0.006 and t = 12.01, P < 0.001) compared to 2009. The multivariate stepwise logistic regression analysis showed that age and region were the risk factors for both measles seropositivity rate and GMC after vaccination. The proportion of high avidity cases increased with age, being significantly higher in 75.31% of cases in patients aged 30-34 years (χ2 = 18.04, P = 0.003). CONCLUSIONS: High immunization coverage in children alone will not be adequate to realizing sufficient levels of population herd immunity, particularly given that the potential susceptibility window in adult. Implementation of supplemental immunization activity (SIA) targeted to appropriate group aged 30-34 years is recommended.

Measles vaccination of young infants in China: A cost-effectiveness analysis.

BACKGROUND: Although global progress in measles control has been realized, achieving elimination has proven difficult in many regions of the world. China has adopted a goal of measles elimination but recent outbreaks predominantly affecting children <8 months who are ineligible for vaccination and incompletely protected by maternal antibodies has impeded progress. We assess the cost-effectiveness of adding an initial measles vaccine dose in China to earlier than the currently recommended 8 months of age. METHODS: We conducted a cost-utility analysis comparing the costs and health benefits associated with adding a measles vaccine dose to the routine schedule at 4, 5, 6 or 7 months compared to the current recommendation for the first dose at age 8 months. A decision analytic model was developed in Microsoft Excel, including five non-severe and two fatal health outcomes associated with measles infection. Model parameters were informed by the literature and surveillance data. Future costs and health benefits were discounted at 3%. Primary outcomes included costs, Quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over a lifetime time horizon. RESULTS: Lowering the recommended age for initiating the measles vaccination series to address susceptibility in children <8 months provided incremental health gains compared to minimal costs at the individual-level. The ICER was most favorable ($232.70 per QALY gain) for administering an initial dose at 4 months of age due to fewer incremental program costs when shifting measles administration to an immunization visit already established under the Chinese vaccination program. CONCLUSION: We found potential beneficial health gains at a minimum cost associated with adding an earlier measles dose <8 months of age in China. Further investigation about disease transmission dynamics is required to more fully assess the tradeoffs of administering measles at a younger age to infants in China.

Assessing measles vaccine failure in Tianjin, China.

Despite increasing global measles vaccination coverage, progress toward measles elimination has slowed in recent years. In China, children receive a measles-containing vaccine (MCV) at 8 months, 18-24 months, and some urban areas offer a third dose at age 4-6 years. However, substantial measles cases in Tianjin, China, occur among individuals who have received multiple MCV doses. This study describes the vaccination history of measles cases 8 months - 19 years old. Data came from measles cases in Tianjin's reportable disease surveillance system (2009-2013), and from a case control study (2011-2015). Twenty-nine percent of those in the surveillance dataset and 54.4% of those in the case series received at least one dose of MCV. The minimum and median time-to-diagnosis since vaccination revealed an increase in time since vaccination for incremental doses. Considerable measles cases in Tianjin occur in vaccinated children, and further research is needed to understand the reasons for vaccine failure.

[Introduction of pertussis surveillance system and evaluation of its operational effect in Tianjin].

The pertussis surveillance system has been established since 2009 in Tianjin, and continuously improved over the past 10 years. This system determines the definition and classification of pertussis, establishes simple and feasible sampling methods and laboratory detection methods in clinical practice, standardizes the report management of pertussis cases and the treatment of epidemic situations. After the implementation of the surveillance system, the number of reported pertussis cases increased from 26 in 2009 to 802 in 2017, the number of diagnosed cases increased from 19 in 2009 to 662 in 2017, the reported incidence rate of pertussis increased from 0.16/100 000 in 2009 to 4.28/100 000 in 2017, and the number of medical institutions of reporting perutssis cases increased from 2 in 2009 to 53 in 2017. The specimen collection rate of the reported cases reached up to 93.66%. These results show that the sensitivity of pertussis surveillance has been improved and show that the data from the surveillance system may reflect more precisely the epidemical characteristics of perutssis in Tianjin.

A novel point-of-care oral anti-HCV assay: Is it reliable for screening hepatitis C virus infection in the era of direct-acting antivirals?

Recent advance in the direct-acting antivirals (DAAs) offers the potentials to eradicate hepatitis C virus (HCV) worldwide and makes universal screening more urgent. A point-of-care (POC) oral anti-HCV assay, the Fortune assay, was developed and its performance was evaluated. Individuals with or without HCV infection were recruited in three Centers. Paired oral and serum samples were tested using the Fortune and InTec anti-HCV assays. The Kehua serum anti-HCV assay served as a supplemental test to verify the discordant results. Some oral samples were also tested using the OraQuick anti-HCV assay. Furthermore, the Fortune assay results were compared with the documented RNA results. Sensitivity, specificity, and accuracy of the Fortune assay was 93.11%, 98.48%, and 96.58%, respectively (n = 1,022). Consistency between the Fortune and OraQuick assays was 96.35% (264/274); the Fortune assay detected additional 8 positive oral samples missed by the OraQuick assay. The Fortune assay demonstrated a 97.46% (115/118) positivity among the viremic patients. Furthermore, its sensitivity was HCV genotype independent. In conclusion, the Fortune assay was highly specific and accurate. It had comparable sensitivity as the serum assays for the diagnosis of active HCV infection. It provides a completely non-invasive and reliable tool for HCV screening in the DAA era.

Dried blood spots: An evaluation of utility in the field.

BACKGROUND: Use of dried blood spots (DBS) offers advantages over serum samples in studies conducted in resource-poor settings. The aim of this study was to compare the number of adequate spots collected across different demographic groups. METHODS: Five DBS were collected from 3316 individuals aged 0-49 years in Tianjin, China for a measles antibody study; DBS were rated "adequate" or "inadequate." Linear regression, with the number of adequate DBS on a card as the outcome variable, was used to test for predictors of DBS adequacy. RESULTS: There were 0 adequate DBS for 23% of participants and 5 adequate DBS for 24%. Mean number of adequate DBS was 1.68 in infants (<12 months), 2.57 (1-9 years), 3.49 (10-29 years), 3.08 (30-49 years). The number of adequate DBS increased over the study; the mean number of adequate DBS for the five years 2011-2015 were 1.21, 2.52, 3.40, 2.22, and 3.62, respectively. DBS quality was not related to measles IgG antibodies. CONCLUSIONS: DBS are an alternative for adults and children but pose challenges in infants, and improve with experience. In a resource-limited environment or in a scenario where more invasive techniques like venipuncture may be less accepted by the study population, DBS can be the preferred technique to efficiently obtain serum specimens for analyte testing.

Measles Antibodies in Mother-Infant Dyads in Tianjin, China.

Background: Many measles cases in Tianjin, China, occur in infants whose mothers were born after widespread vaccination programs. We assessed age-specific decreases in maternal measles antibodies in infants and examined maternal and infant characteristics in relation to infant antibody titers. Methods: Infant and mother dyads were enrolled from a sample of immunization clinics in all Tianjin districts. Participants' antibody titers were measured from dried blood spots. A multivariable log-linear model regressed infant antibody titers onto infant and mother characteristics. Results: Among 551 infants aged ≤8 months, protective levels of measles antibodies were observed in infants whose mothers had measles titers ≥800 IU/mL (mean antibody titer, 542.5 IU/mL) or 400 to <800 IU/mL (mean, 202.2 IU/mL). Compared with infants whose mothers had no history of disease or vaccination, those with a history of disease had 1.60 times higher titers (95% confidence interval, 1.06-2.43). Conclusions: Limited vaccination programs in the 1980s have resulted in many Chinese women with inadequate protection against measles and an accordingly low efficiency of transplacental transmission to a fetus. Current vaccination programs, which target children aged 8 months through adolescence may be ineffective in controlling transmission of measles to infants.

Risk factors for measles among adults in Tianjin, China: Who should be controls in a case-control study?

BACKGROUND: Control groups in previous case-control studies of vaccine-preventable diseases have included people immune to disease. This study examines risk factors for measles acquisition among adults 20 to 49 years of age in Tianjin, China, and compares findings using measles IgG antibody-negative controls to all controls, both IgG-negative and IgG-positive. METHODS: Measles cases were sampled from a disease registry, and controls were enrolled from community registries in Tianjin, China, 2011-2015. Through a best subsets selection procedure, we compared which variables were selected at different model sizes when using IgG-negative controls or all controls. We entered risk factors for measles in two separate logistic regression models: one with measles IgG-negative controls and the other with all controls. RESULTS: The study included 384 measles cases and 1,596 community controls (194 IgG-negative). Visiting a hospital was an important risk factor. For specialty hospitals, the odds ratio (OR) was 4.53 (95% confidence interval (CI): 1.28, 16.03) using IgG-negative controls, and OR = 5.27 (95% CI: 2.73, 10.18) using all controls. Variables, such as age or length of time in Tianjin, were differentially selected depending on the control group. Individuals living in Tianjin ≤3 years had 2.87 (95% CI: 1.46, 5.66) times greater odds of measles case status compared to all controls, but this relationship was not apparent for IgG-negative controls. CONCLUSIONS: We recommend that case-control studies examining risk factors for infectious diseases, particularly in the context of transmission dynamics, consider antibody-negative controls as the gold standard.

A population profile of measles susceptibility in Tianjin, China.

BACKGROUND: Measles is a highly infectious illness requiring herd immunity of 95% to interrupt transmission. Measles is targeted for elimination in China, which has not reached elimination goals despite high vaccination coverage. We developed a population profile of measles immunity among residents aged 0-49 years in Tianjin, China. METHODS: Participants were either from community population registers or community immunization records. Measles IgG antibody status was assessed using dried blood spots. We examined the association between measles IgG antibody status and independent variables including urbanicity, sex, vaccination, measles history, and age. RESULTS: 2818 people were enrolled. The proportion measles IgG negative increased from 50.7% for infants aged 1 month to 98.3% for those aged 7 months. After 8 months, the age of vaccination eligibility, the proportion of infants and children measles IgG negative decreased. Overall, 7.8% of participants 9 months of age or older lacked measles immunity including over 10% of those 20-39 years. Age and vaccination status were significantly associated with measles IgG status in the multivariable model. The odds of positive IgG status were 0.337 times as high for unvaccinated compared to vaccinated (95% CI: 0.217, 0.524). CONCLUSIONS: The proportion of persons in Tianjin, China immune to measles was lower than herd immunity threshold with less than 90% of people aged 20-39 years demonstrating protection. Immunization programs in Tianjin have been successful in vaccinating younger age groups although high immunization coverage in infants and children alone would not provide protective herd immunity, given the large proportion of non-immune adults.

The impact of supplementary immunization activities on the epidemiology of measles in Tianjin, China.

OBJECTIVES: China has repeatedly used supplemental immunization activities (SIAs) to work towards measles elimination, but it is unknown if the SIAs are reaching non-locals - migrants from rural to urban areas. This study characterized temporal trends in measles incidence by local and non-local residency and evaluated the impact of SIAs on measles incidence in Tianjin, China. METHODS: Daily measles case-counts were tabulated separately by residency. These two datasets were combined so that each day had two observations. Poisson regression was conducted using generalized estimating equations with an exchangeable working correlation structure to estimate rate ratios (RRs). RESULTS: There were 12465 measles cases in Tianjin over the 10-year period. The rate of measles was higher in non-locals than locals before the 2008 SIA (RR 3.60, 95% confidence interval (CI) 3.27-3.96), but this attenuated to a RR of 1.22 between the 2008 and 2010 SIAs (95% CI 1.02-1.45). Following the 2010 SIA, non-locals had a lower rate of measles (RR 0.78, 95% CI 0.69-0.87). CONCLUSIONS: The disparity in measles incidence between locals and non-locals was reduced following two SIAs. Sustained public health interventions will be needed to maintain low measles incidence among non-locals given the ongoing migration of people throughout China.

A sera-epidemiological study on pertussis immunity levels among community populations and an analysis of the underlying factors in Tianjin China.

BACKGROUND: The aim of this study is to characterize the sera-epidemiology of pertussis immunity levels among community populations and to identify the underlying factors. Moreover, our study will help resolve new issues encountered during the control and prevention of pertussis reemergence. METHODS: The anti-pertussis antibody levels among community populations were examined using enzyme linked immunosorbent assays (ELISA) over three years. Comparative studies were carried out to assess the efficacy of different types of vaccines. Meanwhile, the duration of protection provided by DTaP within the under-7 age group was subjected to further analysis. RESULTS: The average positive rate for anti-pertussis antibody was 49.15% across all community populations, among which the 4-12 age group showed a rate substantially lower than those of other groups (P<0.001). There was no statistically significant difference in anti-pertussis antibody levels (P=0.977) between people receiving three and four doses of the vaccine. The surveillance results showed that the positive antibody response rate elicited by component pertussis combo (DTcP) vaccines (84.44%) was strikingly higher than that elicited by acellular pertussis combo (DTaP) vaccines (37.22%, P<0.001). More specifically, when given 4 doses of DTcP vaccines, 66.67% of the people showed positive anti-pertussis toxin (PT) antibody levels, which was higher than the ratio of 9.87% (P<0.001) in the case of DTaP vaccines. The positive anti-pertussis antibody levels peaked at 73% within the first five months following vaccination and then gradually decreased to below 20% in four years. The positive rate was inversely correlated with the length of time after vaccination (r=-0.929, P=0.003). CONCLUSIONS: The anti-pertussis antibody levels were not only relatively low among community populations, but also dropped excessively rapidly among vaccinated populations. Natural infection is an important contributor to the high pertussis immunity levels seen in adolescents and adults. The efficacy of DTaP remains to be improved.

The epidemiology of measles in Tianjin, China, 2005-2014.

BACKGROUND: Measles incidence in China has declined over the last decade and elimination is targeted by 2020. Despite increases in routine immunization services and supplementary immunization activities (SIAs), periodic outbreaks continue to occur. In this paper, we examine measles epidemiology during 2005-2014 in Tianjin, China. METHODS: Measles case data were extracted from a web-based communicable disease surveillance system. We examined the socio-demographic characteristics of measles case patients, including age, sex, urbanicity, residency status, and vaccination history. Demographic characteristics of cases were compared with the general population. RESULTS: From January 1, 2005 to December 31, 2014, 12,466 measles cases in Tianjin were reported. Among the cases, 7179 (57.6%) were male and 5287 (42.4%) were female. Over time, more cases occurred in adults, and for the 2711 cases in 2014, the majority were either infants <1 year (558, 20.58%) or adults ≥ 20 years (2043, 75.36%). Municipal-wide SIAs in Tianjin occurred in 2008 and 2010 with reduction in measles cases the following year for both (189 cases in 2009, and 37 cases in 2011). The number of cases rebounded to pre-SIA levels or higher within 1-3 years following each SIA: 1990 cases in 2010 and 2711 cases in 2014. Vaccination status was reported as "none" or "unknown" for 84% of all reported measles cases. CONCLUSIONS: Despite the general decline in cases, measles outbreaks continue to occur. Although the SIAs reduce numbers in their immediate aftermath, case counts rebound 1-3 years after the intervention. Continued monitoring of cases through disease surveillance activities accompanied by targeted immunization activities, including to adults, can help ensure progress toward elimination.

Timely measles vaccination in Tianjin, China: a cross-sectional study of immunization records and mothers.

BACKGROUND: Measles is a highly infectious disease, and timely administration of two doses of vaccine can ensure adequate protection against measles for all ages in a population. This study aims to estimate the proportion of children aged 8 months to 6 years vaccinated on time with measles-containing vaccines (MCV) and vaccinated during the 2008 and 2010 measles supplementary immunization activities. This study also characterizes differences in mean age at vaccination and vaccination timeliness by demographic characteristics, and describes maternal knowledge of measles vaccination. METHODS: Immunization records were selected from a convenience sample of immunization clinics in Tianjin, China. From the records, overall vaccination coverage and timely vaccination coverage were calculated for different demographic groups. Mothers were also interviewed at these clinics to ascertain their knowledge of measles vaccination. RESULTS: Within the 329 immunization clinic records, child's birth year and district of residence were found to be significant predictors of different measures of vaccine timeliness. Children born in 2009 had a lower age at MCV dose 2 administration (17.96 months) than children born in 2005 (22.00 months). Children living in Hebei, a district in the urban center of Tianjin were less likely to be vaccinated late than children living in districts further from the urban core of Tianjin. From the 31 interviews with mothers, most women believed that timely vaccination was very important and more than one dose was very necessary; most did not know whether their child needed another dose. CONCLUSIONS: When reviewing MCV coverage in China, most studies do not consider timeliness. However, this study shows that overall vaccination coverage can greatly overestimate vaccination coverage within certain segments of the population, such as young infants.

Effectiveness of 10-year vaccination (2001-2010) on Hepatitis A in Tianjin, China.

Vaccination is an effective strategy to prevent and control the transmission of hepatitis A. Hepatitis A immunization program has been taken into effect since 2001 in Tianjin, China. This study evaluated the effectiveness of strategies in the prevention and control of hepatitis A. Data of serological survey, annual hepatitis A incidence, immunization coverage and the positive rate of hepatitis A IgG before and after the immunization program in residents under 15 years old were used to do the analysis. The results indicated that hepatitis A vaccine induced a striking decrease of hepatitis A incidence and a significant increase in the positive rate of anti-HAV IgG among the children younger than 15 years old. Hepatitis A vaccination in children was proved to be effective in the prevention and control of hepatitis A in Tianjin, China.

[Evaluation on the hepatitis A vaccine in preventing hepatitis A infection in Tianjin, from 2000 to 2011].

OBJECTIVE: Hepatitis A immunization strategies were carried out in 2001 in Tianjin. We wanted to evaluate the effectiveness of the strategies related to hepatitis A control programs and to provide the basis for further modification of the strategies. METHODS: Descriptive epidemiology study was used to analyze the hepatitis A epidemic situation in 2000-2011 in Tianjin and to evaluate the disease reporting system. Hepatitis A vaccine coverage of target population and serum epidemiological study were carried out in 1999, 2005 and 2010 to check on the hepatitis A antibody levels so as to evaluate the immuno-barrier condition in the normal population. Cox-Stuart test was used to analyze the epidemic trend of hepatitis A and other intestinal infectious diseases in Tianjin. RESULTS: The incidence rate of hepatitis A decreased from 2.89/100 000 in 2000 to 0.12/100 000 in 2011, and the percentage of hepatitis A in all types of viral hepatitis decreased from 8.02% in 2000 to 0.48% in 2011 in Tianjin. The positive rates of hepatitis A antibody also increased in the residents. CONCLUSION: The hepatitis A vaccination program was successful in the programs on prevention and control of hepatitis A in Tianjin, China.

[Evaluation on the role of hepatitis A vaccine in the prevention and control of hepatitis A in Tianjin city].

OBJECTIVE: To evaluate the effects of prevention and control strategies on hepatitis A. METHODS: Surveillance data on hepatitis A from 1990 to 2006 in Tianjin was analyzed, and the coverage rate of hepatitis A vaccine among targeted population was estimated, to compare the anti-HAV IgG level of children younger than 15 years old in 1999 and in 2005. RESULTS: Results showed that a) the morbidity of hepatitis A decreased from 25.26/10(5) in 1990 to 0.82/10(5) in 2006; b) the ratio of hepatitis A in viral hepatitis decreased from 30.43% in 1990 to 1.05% in 2006; c) the estimated coverage rate was 72.7%; d) the positive rate of anti-HAV among children younger than 15 years old in 2005 was distinctly higher than that in 1999. CONCLUSION: Positive results showed that it was successful to use hepatitis A vaccine as the strategy to prevent and control hepatitis A in the past five years in Tianjin.