Huiming Luo

The seroepidemiology of Immunoglobulin G antibodies against pertussis toxin in China: a cross sectional study

BackgroundPertussis is a reported vaccine-preventable respiratory disease in China. Because the routine laboratory methods for diagnosis are not in use, the reported cases are mainly in infants with classical paroxysmal cough and the true incidence related to pertussis is most likely under estimated. In China, however, few studies have attempted to address this issue. The purpose of this cross sectional study was to estimate the incidence rates using the method of sero-epidemiology of immunoglobulin (Ig) G antibodies against pertussis toxin (PT) among healthy populations in China.MethodsBlood samples were obtained from 1313 healthy individuals aged 0 to 95 years in Guangdong province of China throughout September 2010. Serum IgG antibodies against PT were determined by commercial ELISA kits. Subjects with concentration of anti-PT IgG higher than 30 IU/mL were indicated to have recent Bordetella pertussis infection, if they have not received a booster dose of pertussis vaccine within one year.ResultsOf the 1313 study subjects, 117 (8.91%) were found to have anti-PT antibodies higher than 30 IU/mL. The estimated incidence of recent infection was thus 9395 per 100,000 for individuals older than 7 years. Peaks of the estimated incidence rate of recent infection were found to be 11561 per 100,000 in age group of 41–50 years and 11428 per 100,000 in the group aged 13–19 years.ConclusionsOur study indicated that B.pertussis infections are considerablely common, particularly in adolescents and adults in China. The study also stresses the importance of laboratory diagnosis for pertussis and employment of booster dose of pertussis vaccine in adolescents and adults in this country.

Prevalence of asymptomatic Bordetella pertussis and Bordetella parapertussis infections among school children in China as determined by pooled real-time PCR: A cross-sectional study

Abstract Background: Studies have documented that older children and adolescents act as a reservoir of Bordetella pertussis infection for young infants who have not yet completed their primary immunization schedule. Asymptomatic pertussis infection has been reported during outbreaks. This cross-sectional study aimed to investigate whether B. pertussis and Bordetella parapertussis can colonize the nasopharynx of healthy school children, using culture and pooled real-time PCR with targets for insertion sequences IS481 and IS1001. Methods: Nasopharyngeal (NP) swabs were taken from 629 asymptomatic school children aged 7 to 15 y in 4 counties of China during the period July–September 2011. The number of subjects included in each county ranged from 153 to 165. The 4 counties selected are located in the north, south, east, and southwest regions of China. NP swabs were inoculated onto Regan–Lowe agar for isolation of suspected Bordetella organisms. Pooled real-time PCRs were used to detect B. pertussis and B. parapertussis based on the IS481 and IS1001 targets separately. Results: Of the 629 subjects, 2 (0.3%) and 30 (4.8%) were confirmed to be culture-positive and PCR-positive, respectively, for B. pertussis, and 1 (0.2%) and 13 (2.1%) were confirmed to be culture-positive and PCR-positive, respectively, for B. parapertussis. All culture-positive samples were also PCR-positive. Furthermore, positive B. pertussis and B. parapertussis samples were found in all counties. Conclusions: Our results indicate that asymptomatic B. pertussis infections are common in school children in China, and asymptomatic B. parapertussis infections are more prevalent than previously documented.

Measles vaccine coverage estimates in an outbreak three years after the nation-wide campaign in China: implications for measles elimination, 2013.

BackgroundChina is approaching measles elimination, but indigenous measles still circulates. County L in China has reported measles-containing vaccine (MCV) coverage rates >95% since 2000. Despite high reported coverage, a large measles outbreak occurred among young children in L County. We measured MCV coverage using 5 different methods during an investigation on this outbreak and compared our estimates with reported rates.MethodsReported coverage rates are determined by aggregating clinic-based data across the county: doses administered in each clinic divided by the number of children registered in each clinic. Our methods estimated coverage for the 2010–2012 birth cohort, and were (1) administrative method: doses administered in clinics divided by the birth cohort recorded in the Statistical Year Book, (2) house-to-house convenience-sample survey of children living near cases, (3) vaccination clinic records review, (4) determination of a convenience sample of measles outbreak cases’ vaccination statuses and using the field vaccine efficacy outbreak equation to estimate population coverage, and (5) a seroprevalence survey using a convenience sample of residual blood samples from hospitals.ResultsThe measles outbreak totaled 215 cases, representing an incidence of 195.8 per million population. Our estimated MCV coverage rates were: (1) administrative method: 84.1%-87.0% for MCV1 and 80.3%-90.0% for MCV2, (2) in-house survey: 83.3% of 9–17 month children received MCV1, and 74.5% of 24–47 month children received MCV2, (3) clinic record review: 85.5% of 9–17 month children received MCV1, and 73.2% of 24–59 month children received MCV2, (4) field VE method: 83.6% of 9–47 month children received one or more MCV doses, and (5) serology: seropositive rates were <80% in the 12–17 and 18–23 month age cohorts.ConclusionsCompared with reported coverage >95%, our 5 coverage assessments all showed substantially lower coverage. China should evaluate guidelines for reporting vaccination coverage and identify feasible improvements to the assessment methods.

Investigation of a Measles Outbreak in China to Identify Gaps in Vaccination Coverage, Routes of Transmission, and Interventions

Background A measles outbreak occurred in a western county of China in 2013, the year after China’s historic nadir of measles. We conducted a field investigation to identify gaps in measles vaccination coverage and immunization program weaknesses, and to provide recommendations for measles outbreak response and immunization program improvement. Methods We analyzed surveillance data from 2008 to 2013 to describe the measles epidemiology of the county. Measles-containing vaccine coverage was estimated using two methods: previously-reported administrative coverage and an estimation of coverage by clinic-kept vaccination records (n = 542). We conducted a rapid field coverage assessment in a migrant population village to evaluate coverage after emergency vaccination. We conducted a review of hospital records of measles cases to address the role hospital transmission played during the early stage of this outbreak. Results There were 153 cases in the outbreak, primarily among children too young to vaccinate, unvaccinated children less than 3 years old, and adults. Measles-containing vaccine coverage by the field assessment showed that 20% of children aged 8–17 months had zero doses, and 9% of ≥2 years old children had fewer than two doses. The vaccination statuses of all adult cases were either zero doses or unknown. At least 61% of cases had been hospitalized. The proportion of cases who had been hospital-exposed 7 to 21 days prior to rash onset decreased from 52% to 22% after hospitals strengthen their isolation measures. Conclusions This outbreak was a result of measles vaccination coverage gaps among young children and adults, and insufficient hospital isolation of cases. The lower coverage seen in the field estimation compared with reported coverage showed that reported coverage could have been overestimated. Hospitals were sites of transmission in the early stage of the outbreak. A strict hospital isolation policy could decrease spread of measles. Emergency vaccination was associated with stopping measles transmission in low coverage areas.

An Outbreak of Type Π Vaccine-Derived Poliovirus in Sichuan Province, China: Emergence and Circulation in an Under-Immunized Population

Background During August 2011–February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs) occurred in Sichuan Province, China. Methods A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. Results One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8–1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5–12 nucleotides (nt) and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months) reported in Ngawa Prefecture in 2011, 4 (57.1%) cases (including 2 polio cases) did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs) were conducted in February–May, 2012, and the strain has not been isolated since. Conclusion High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary.

Enhanced surveillance of acute flaccid paralysis following importation of wild poliovirus in Xinjiang Uygur Autonomous Region, China

BackgroundAfter being polio free for more than 10 years, an outbreak occurred in China in 2011 in Xinjiang Uygur Autonomous Region (Xinjiang) following the importation of wild poliovirus (WPV) originating from neighboring Pakistan.MethodsTo strengthen acute flaccid paralysis (AFP) surveillance in Xinjiang, “zero case daily reporting” and retrospective searching of AFP cases were initiated after the confirmation of the WPV outbreak. To pinpoint all the polio cases in time, AFP surveillance system was expanded to include persons of all ages in the entire population in Xinjiang.ResultsTotally, 578 AFP cases were reported in 2011 in Xinjiang, including 21 WPV cases, 23 clinical compatible polio cases and 534 non-polio AFP cases. Of the 44 polio cases, 27 (61.4%) cases were reported among adults aged 15–53 years. Strengthening AFP surveillance resulted in an increase in the number of non-polio AFP cases in 2011 (148 children < 15 years) compared with 76 cases < 15 years in 2010. The AFP surveillance system in Xinjiang was sensitive enough to detect polio cases, with the AFP incidence of 3.28/100,000 among children < 15 years of age.ConclusionsIncorporating adult cases into the AFP surveillance system is of potential value to understand the overall characteristics of the epidemic and to guide emergency responses, especially in countries facing WPV outbreak following long-term polio free status. The AFP surveillance system in Xinjiang was satisfactory despite limitations in biological sample collection.

Prevalence of meningococcal meningitis in China from 2005 to 2010.

BACKGROUND We aimed to estimate the prevalence and epidemiologic characteristics of meningococcal meningitis (MM) in mainland China (excluding Taiwan, Hong Kong, and Macau) and to provide reference data for controlling the outbreak and prevalence of MM. METHODS Data from the National Notifiable Diseases Registry System and the MM case information reporting system from 2005 to 2010 as well as data from the MM Surveillance System were used. RESULTS The morbidity of MM for the whole country was, on average, 0.09 cases per 100,000 (range 0.02 [2010]-0.18 [2005] cases per 100,000) from 2005 to 2010, the incidence rate was highest in the Xinjiang autonomous region (average 0.56 cases per 100,000), and the majority of cases came from Anhui province (average 0.32 cases per 100,000). Morbidity was highest in children under 1 year old (average 0.60 cases per 100,000). The proportion of laboratory-confirmed cases of serogroups A, B, and C were 37.2, 11.5 and 42.7, respectively, from 2005 to 2010. CONCLUSIONS The incidence level declined year-to-year in mainland China. Children and students are the most at risk groups. The proportion of serogroup C cases has increased year-to-year, and new cases of serogroup W135 have been found. Controlling the epidemic of serogroup C and preventing outbreaks of serogroup B and W135 represent major future challenges.

Demographic transition and the dynamics of measles in six provinces in China: A modeling study

Background Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China. Methods and findings We fit a novel time-varying catalytic model to three decades of age-specific measles case reporting in six provinces in China to quantify the change in the age-specific force of infection for measles virus over time. We further quantified the impact of supplemental vaccination campaigns on the reduction of susceptible individuals. The force of infection of measles has declined dramatically (90%–97% reduction in transmission rate) in three industrialized eastern provinces during the last decade, driving a concomitant increase in both the relative proportion and absolute number of adult cases, while three central and western provinces exhibited dynamics consistent with endemic persistence (24%–73% reduction in transmission rate). The reduction in susceptible individuals due to supplemental vaccination campaigns is frequently below the nominal campaign coverage, likely because campaigns necessarily vaccinate those who may already be immune. The impact of these campaigns has significantly improved over time: campaigns prior to 2005 were estimated to have achieved less than 50% reductions in the proportion susceptible in the target age classes, but campaigns from 2005 onwards reduced the susceptible proportion by 32%–87%. A limitation of this study is that it relies on case surveillance, and thus inference may be biased by age-specific variation in measles reporting. Conclusions The age distribution of measles cases changes in response to both demographic and vaccination processes. Combining both processes in a novel catalytic model, we illustrate that age-specific incidence patterns reveal regional differences in the progress to measles elimination and the impact of vaccination controls in China. The shift in the age distribution of measles susceptibility in response to demographic and vaccination processes emphasizes the importance of progressive control strategies and measures to evaluate program success that anticipate and react to this transition in observed incidence.

Measles imported to the United States by children adopted from China.

In July 2013, the National Immunization Program of China was notified by the US Centers for Disease Control and Prevention that measles was detected in 3 newly adopted, special needs children with cerebral palsy (CP) from China. We report an investigation of measles transmission in China that led to infection of these children. Interviews were conducted with welfare institute staff and panel physicians; health records of the potentially exposed population were reviewed; and immunization coverage was assessed among institute residents. Five residents with CP, all unvaccinated against measles, among who were the 3 adoptees, were linked epidemiologically into 3 generations of measles transmission antecedent to the US outbreak. In a random sample of residents, first dose of measles containing vaccine (MCV1) and MCV2 coverage was 16 of 17 (94%) and 7 of 11 (64%) among children with CP, and 100% (32 of 32) and 96% (21 of 22) among children without CP. Vaccinators reported reluctance to vaccinate children with CP because the China pharmacopeia lists encephalopathy as a contraindication to vaccination. Panel physicians reported to investigators no necessity of vaccination for adoptees to the United States if US parents sign an affidavit exempting the child from vaccination. We recommend that the China pharmacopeia vaccine contraindications be reviewed and updated, the United States should reconsider allowing vaccination exemptions for internationally adopted children unless there are true medical contraindications to vaccination, and US pediatricians should counsel adopting parents to ensure that their child is up-to-date on recommended vaccinations before coming to the United States.

Risk factors for measles infection in 0–7 month old children in China after the 2010 nationwide measles campaign: A multi-site case–control study, 2012–2013 ☆

Introduction: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. We performed a case–control study in six Chinese provinces during January 2012 through June 2013 to identify risk factors for measles infection among children aged 0–7 months. Methods: Children with laboratory-confirmed measles were neighborhood matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. Adjusted matched odds ratios (mOR) and 95% confidence intervals (CIs) were calculated by multivariable conditional logistic modeling. We calculated attributable fractions for risk factors that could be interpreted as causal. Results: Eight hundred thirty cases and 2303 controls were enrolled. In multivariable analysis, male sex (mOR 1.6 [1.3, 2.0]), age 5–7 months (mOR 3.9 [3.0, 5.1]), migration between counties (mOR 2.3 [1.6, 3.4]), outpatient hospital visits (mOR 9.4 [6.6, 13.3]) and inpatient hospitalization (mOR 107.1 [48.8, 235.1]) were significant risk factors. The calculated attributable fractions for hospital visits was 43.1% (95% CI: 40.1, 47.5%) adjusted for age, sex and migration. Conclusions: Hospital visitation was the largest risk factor for measles infection in infants. Improved hospital infection control practices would accelerate measles elimination in China.