Recruitment into antibody prevalence studies: a randomized trial of postcards vs. letters as invitations.

BACKGROUND: In a potential epidemic of an emerging infection, representative population-based serologic studies are required to determine the extent of immunity to the infectious agent, either from natural infection or vaccination. Recruitment strategies need to optimize response rates. METHODS: Within a seroepidemiologic study to determine the true burden of SARS-CoV2 infection in two Bay Area counties, we evaluated whether letter (L) or postcard (P) invitations with reminders were more effective at recruiting participant households. Using geographic, probability-based sampling, 9,999 representative addresses, split between Santa Clara and Solano counties, were randomized to receive an initial invitation (L or P); a randomized reminder mailing sent two weeks later to all non-respondents created four mailing type groups (L/L, L/P, P/L, P/P). Interested households provided contact information via survey to perform blood spot collection at home for testing and then receive SARS-CoV2 serology results. Comparison of demographics among respondents and non-respondents used census tract data. RESULTS: Receiving any reminder mailing increased household response rates from 4.2% to between 8-13% depending on mailing combination. Response rates from two letters were 71% higher than from two postcards (13.2% vs. 7.7%, OR = 1.83 [95% CI: 1.5-2.2]). Respondents were older, more educated and more likely white than non-respondents. Compared to Solano county, Santa Clara county had different demographics and increased household response rates (L/L: 15.7% vs 10.7%; P/P: 9.2% vs. 6.1%; p < 0.0001); the effect of mailing types, however, was the same (L/L vs. P/P: Santa Clara: OR = 1.83 [95% CI: 1.4-2.3]; Solano: OR = 1.84 [95% CI:1.4-2.5]). CONCLUSION: Letters, as both invitations and reminders, are a more effective recruitment tool than postcards and should be considered when seeking a representative population-based sample for serological testing.

Comparison of population-based measles-rubella immunoglobulin G antibody prevalence between 2014 and 2019 in Lao People's Democratic Republic: Impacts of the national immunization program.

OBJECTIVES: We evaluated the effectiveness of the Lao People's Democratic Republic's measles-rubella immunization program using the seroprevalence from two cross-sectional surveys. METHODS: The nationwide surveys occurred in 2014 and 2019 using a multistage cluster sampling, both requiring samples from 2184 individuals from 52 randomly selected villages. Immunoglobulin G titers, measured using enzyme-linked immunosorbent assay, were considered positive at ≥120 mIU/ml (measles) and ≥10 IU/ml (rubella). We calculated the vaccination-related reduction in the force of rubella infection and the number of congenital rubella syndrome cases averted in 2019. RESULTS: We collected 2135 (women: 55.2%, mean age: 23.2 years) and 2001 (52.7%, 23.1 years) samples in 2014 and 2019, respectively. During 2014-2019, immunoglobulin G prevalence increased from 83.9% (95% confidence interval [CI]: 83.8-84.0) to 98.3% (97.7-98.8) for measles and from 75.4% (75.3-75.5) to 87.8% (86.4-89.2) for rubella. The most plausible reduction in the average force of rubella infection was 100% (95% CI: 28-100) since vaccination started, averting 78 (95% CI: 42-128) congenital rubella syndrome cases in 2019. CONCLUSION: This is the first population-based study for measles and rubella at two different time points in developing countries. Measles and rubella seroprevalence increased significantly during 2014-2019, greatly exceeding the immunity thresholds for their elimination.

Impact of hepatitis B vaccination programs in Vietnam evaluated by estimating HBsAg prevalence.

Background: Vietnam introduced a 3-dose hepatitis B (HBV) immunization program comprising 1 dose immediately after birth and 2 or 3 in infancy in the past 20 years, but the impact of the vaccine has not been systematically evaluated. Thus, we conducted this survey aiming to estimate the age-specific chronic HBV prevalence in the general population and to evaluate HBV immunization effectiveness. Methods: Population-based, four-stage cluster sampling was used in the South Central Coast region of Vietnam. The point-of-care Determine rapid test was used to assess hepatitis B surface antigen (HBsAg) positivity. Results: A total of 2,075 samples were included in the study. HBsAg prevalence was significantly higher among adults aged 20-39 years than in the population aged 1-19 years (8.0% [95% confidence interval 5.0-12.0] vs. 2.0% [95% confidence interval 1.0-6.0], p<0.01). HBsAg prevalence decreased after implementation of the 3-dose vaccination schedule during infancy from 1997 to 2002, whereas the change in prevalence after implementation of the birth dosing was not significant. A slight increase in HBsAg prevalence was observed for the cohort born in 2011, 2012, and 2013, when there was a vaccine shortage and media reports of immunization resistance. Conclusions: This is the first population-based assessment of the introduction of the HBV vaccine in Vietnam performed by estimating the HBsAg prevalence across a wide range of ages. The results showed that the HBV immunization policy effectively reduces HBsAg prevalence in general, although birth dosing of the vaccine and low immunization coverage should be carefully monitored.

Community-based survey to assess seroprevalence of poliovirus antibodies in far-north Cameroon in 2020.

Background: This study assessed seroprevalence of poliovirus antibodies in children from selected poliovirus high-risk areas of the Far North region of Cameroon which serves to monitor polio immunization program. Methods: This was a community-based cross-sectional seroprevalence survey involving collection of dried blood specimens (DBS) among children aged 12-59 months (n = 401). Multi-stage cluster sampling using GIS was applied to select the study sample. Collected DBS were analysed with microneutralization assays for poliovirus neutralizing antibody levels. Results: The overall seroprevalence of types 1, 2 and 3 neutralizing antibodies were 86.8 % (95 % confidence interval [CI]: 83.1-89.8), 74.6 % (95 % CI: 70.1-78.6) and 79.3 % (95 % CI: 75.1-83.0), respectively. Median titers (log2 scale) for type 1, 2 and 3 were 7.17 (6.5-7.5), 5.17 (4.83-5.5), and 6.17 (5.5-6.5), respectively. There was an increasing trend in median titers and seroprevalence with age, statistically significant between the youngest and oldest age groups (p < 0.001). Conclusion: Though there were several opportunities for vaccination through supplementary immunization activities (SIA) and routine immunization (RI), seroprevalence levels were low for all three serotypes, particularly for type 2. This highlights the need to strengthen RI and SIA quality coverage. Low population immunity makes Cameroon vulnerable to new importations and spread of polioviruses.

Comparison between a rapid diagnostic test and dried blood spot-based immunoassay for hepatitis B surface antigen testing: Performance and cost implications in a population-based serosurvey in Vietnam.

OBJECTIVES: This study aimed to determine the agreement between a rapid diagnostic test (RDT) and a dried blood spot (DBS)-based electrochemiluminescence immunoassay (ECLIA) of hepatitis B surface antigen and to compare the costs of conducting serosurveys using RDTs and DBS in a field setting. METHODS: A serosurvey was conducted in the South Central Coast region of Vietnam in May 2019. Participants aged 1-39 years were recruited using a four-stage random sampling method and tested for hepatitis B surface antigen using an RDT kit (Alere Determine) and a DBS-based ECLIA. The agreement between the RDT and the DBS-based ECLIA was assessed using cross-tabulation and Cohen kappa. Cost data were categorized by input (personnel, transportation, field consumables, laboratory consumables, and capital item/overhead) and survey phase (survey preparation, data/biospecimen collection, laboratory testing, and coordination). RESULTS: A total of 2072 participants were analyzed. There was a 99% agreement between the RDT and the DBS-based ECLIA results, with a Cohen kappa of 0.9. The estimated cost of conducting a serosurvey by DBS was UD $75,291, whereas RDT was $53,182. CONCLUSION: RDTs and DBS-based ECLIA provide test results with high agreements. RDTs are a better option in terms of cost, whereas the DBS-based ECLIA may be useful when evaluating multiple infectious diseases.

SARS-CoV-2 seroprevalence and antibodies persistence among health care workers after the first COVID-19 wave in nine hospitals in Western France.

OBJECTIVES: To estimate the SARS-CoV-2 IgG seroprevalence rate in healthcare workers (HCWs) from Western France after the first 2020 wave, its determinants and the kinetics of total SARS-CoV-2 antibodies. PATIENTS AND METHODS: Overall, 9,453 HCWs responded to a self-questionnaire and underwent a lateral flow immunoassay to assess SARS-CoV-2 IgG presence. For 72 HCWs who tested positive, total anti-nucleocapsid antibodies were assessed at day 0, 30, and 90. RESULTS: SARS-CoV-2 IgG seroprevalence rate was 1.06 % [0.86 %-1.27 %]. Factors associated with IgG presence were gender, performing upper respiratory tract samples, contact with HCWs or household members diagnosed with COVID-19. Total antibodies decreased between day 0 and day 90, with anosmia or ageusia, and were higher in HCWs older than 50 years. CONCLUSION: We reported a low prevalence rate of IgG and identified several risk factors associated with its presence and persistence of total antibodies. Additional studies are needed to confirm these observations.

Adjusting COVID-19 Seroprevalence Survey Results to Account for Test Sensitivity and Specificity.

Population-based seroprevalence surveys can provide useful estimates of the number of individuals previously infected with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and still susceptible, as well as contribute to better estimates of the case-fatality rate and other measures of coronavirus disease 2019 (COVID-19) severity. No serological test is 100% accurate, however, and the standard correction that epidemiologists use to adjust estimates relies on estimates of the test sensitivity and specificity often based on small validation studies. We have developed a fully Bayesian approach to adjust observed prevalence estimates for sensitivity and specificity. Application to a seroprevalence survey conducted in New York State in 2020 demonstrates that this approach results in more realistic-and narrower-credible intervals than the standard sensitivity analysis using confidence interval endpoints. In addition, the model permits incorporating data on the geographical distribution of reported case counts to create informative priors on the cumulative incidence to produce estimates and credible intervals for smaller geographic areas than often can be precisely estimated with seroprevalence surveys.

Estimating seroprevalence of SARS-CoV-2 in Ohio: A Bayesian multilevel poststratification approach with multiple diagnostic tests.

Globally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 59 million people and killed more than 1.39 million. Designing and monitoring interventions to slow and stop the spread of the virus require knowledge of how many people have been and are currently infected, where they live, and how they interact. The first step is an accurate assessment of the population prevalence of past infections. There are very few population-representative prevalence studies of SARS-CoV-2 infections, and only two states in the United States-Indiana and Connecticut-have reported probability-based sample surveys that characterize statewide prevalence of SARS-CoV-2. One of the difficulties is the fact that tests to detect and characterize SARS-CoV-2 coronavirus antibodies are new, are not well characterized, and generally function poorly. During July 2020, a survey representing all adults in the state of Ohio in the United States collected serum samples and information on protective behavior related to SARS-CoV-2 and coronavirus disease 2019 (COVID-19). Several features of the survey make it difficult to estimate past prevalence: 1) a low response rate; 2) a very low number of positive cases; and 3) the fact that multiple poor-quality serological tests were used to detect SARS-CoV-2 antibodies. We describe a Bayesian approach for analyzing the biomarker data that simultaneously addresses these challenges and characterizes the potential effect of selective response. The model does not require survey sample weights; accounts for multiple imperfect antibody test results; and characterizes uncertainty related to the sample survey and the multiple imperfect, potentially correlated tests.

Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities.

BACKGROUND: In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system among children born to infected mothers. Thus, they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies. METHODS: The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients' houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1-4 (DENV1-4) and Japanese encephalitis virus (JEV) antibodies using PRNT90. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity. RESULTS: Out of all 18 index cases, 9 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 43.7% (35.9-51.6%) and 29.7% (23.3-36.0%) in general population, and 24.3% (20.1-28.8%) and 12.8% (9.7-16.5%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index's houses. However, being elderly was associated with seropositivity. DENV1-4 and JEV neutralizing antibodies were present in most ZIKV-positive and negative subsamples. CONCLUSION: Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.

Seroprevalence of antibodies against diphtheria, tetanus, and pertussis among healthy Thai adolescents.

OBJECTIVE: To determine the seroprevalence of antibodies against of diphtheria, tetanus, and pertussis among Thai adolescents. METHODS: A cross-sectional study was conducted among Thai adolescents aged 11-20 years who had completed five doses of diphtheria, tetanus, and pertussis (DTP)-containing vaccine during childhood, either diphtheria toxoid, tetanus toxoid, whole-cell pertussis (DTwP) or diphtheria toxoid, tetanus toxoid, acellular pertussis (DTaP) vaccine. Protective antibodies against diphtheria, tetanus, and pertussis were defined as anti-diphtheria toxoid IgG ≥0.1 IU/ml, anti-tetanus toxoid IgG ≥0.1 IU/ml, and anti-Bordetella pertussis toxin IgG ≥5 IU/ml, respectively. RESULTS: Of 220 adolescents (median age 16 years), 45% had received a tetanus toxoid, reduced diphtheria toxoid (Td) booster vaccine during adolescence, and none (0%) had received a tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) booster vaccine. Overall, 50%, 99%, and 57% of adolescents demonstrated protective antibodies against diphtheria, tetanus, and pertussis, respectively. The geometric mean concentrations (GMCs) of antibodies against diphtheria (p = 0.06) and tetanus (p < 0.001) were higher among adolescents who had received Td vaccine. Nevertheless, the antibody levels against both diseases waned over time, regardless of Td booster vaccination. Likewise, pertussis antibody levels gradually declined after the fifth childhood dose of DTwP/DTaP vaccine. CONCLUSIONS: Approximately half of these healthy Thai adolescents had not maintained protective antibodies against diphtheria and pertussis. A booster vaccination with diphtheria toxoid and/or acellular pertussis-containing vaccines is a crucial strategy to prevent such diseases in this population.

Serological evidence of ongoing transmission of dengue virus in permanent residents of Key West, Florida.

INTRODUCTION: Dengue fever is the most important mosquito-borne viral disease in the world, with 40% of the global population at risk of infection. Dengue virus is responsible for infections in over 100 countries, including the Americas and Caribbean Basin; however, it has been largely eradicated from the United States through the implementation of effective vector control programs. However, between 2009 and 2010, 27 permanent residents of Key West, Florida, were reported to have locally acquired infections, marking the first autochthonous cases detected in Florida since 1934. Despite this recent and unusual transmission, and the potential risk of serious illness associated with sequential infections, no active surveillance had been conducted since. MATERIALS AND METHODS: A serosurvey of permanent residents of Key West, Florida, was conducted in March of 2012. After informed consent, enrolled participants (n=173) were given a dengue virus rapid diagnostic test and completed a corresponding questionnaire. RESULTS: The presence of immunoglobulin G (IgG) antibodies was indicated in 12 participants (6.9%), all of whom reported travel to endemic countries within the past 2 years. Surprisingly, six participants (3.5%) without any recent travel outside the state of Florida gave positive results for IgM antibodies. The presence of birdbaths and bromeliads on the property and sleeping outdoors emerged as significant factors related to previous exposure, whereas home air conditioning without the use of open windows and the use of mosquito repellent were protective. CONCLUSIONS: These findings suggest local transmission occurred in Key West in early 2012, indicating that transmission may not have subsided in 2010.

Seroepidemiology of hepatitis B virus infection among adults in Singapore: a 12-year review.

We undertook a national hepatitis B seroprevalence study to assess the seroprevalence of hepatitis B virus (HBV) markers in the adult population in Singapore in 2010 and make comparisons with the seroprevalence in 1998 and 2004. The study involved residual sera from national health surveys conducted every six years since 1998. The tests for HBV markers were carried out using commercial chemiluminescent microparticle immunoassay. In 2010, the prevalence of hepatitis B surface antigen (HBsAg) among 3293 Singapore residents aged 18-79 years was 3.6% (95% confidence interval [CI] 2.9-4.2%). Hepatitis B e antigen (HBeAg) was detected in 4.2% of those who were HBsAg positive. About 22.5% (95% CI 21.1-23.9%) were positive for antibody to hepatitis B core antigen (anti-HBc). The overall population immunity to HBV, as determined by antibody to hepatitis B surface antigen (anti-HBs)≥ 10 mIU/mL, was 43.9% (95% CI 42.2-45.6%). Among young adults below 30 years of age, HBsAg prevalence (1.1%) was half that in 1998 and 2004, and in those positive for HBsAg, none was positive for HBeAg in 2010, compared to 20.8% in 1998 and 15.8% in 2004. In this age group, anti-HBc prevalence also decreased significantly from 22.1% in 2004 to 4.4% in 2010, while anti-HBs (≥ 10 mIU/mL) prevalence increased significantly from 27.9% in 1998 to 43.3% in 2010 (p<0.001). The national childhood HBV immunisation and catch-up programmes implemented in 1987 and 2001-2004, respectively, had a significant impact in reducing HBV infection and in raising the immunity of the adult population 18-29 years of age.

Comparison of hemagglutination inhibition assay and enzyme immunoassay for determination of mumps and rubella immune status in health care personnel.

BACKGROUND: Screening tests are available to determine immunity to vaccine-preventable diseases, such as mumps and rubella. We aimed to define better assay for detecting immune status of health care personnel to vaccine-preventable diseases. METHODS: Mumps and rubella antibodies of health care personnel at Shimane University Hospital were examined by hemagglutination inhibition assay (HI), comparing with those by enzyme immunoassay (EIA). RESULTS: A total of 910 sera from health care personnel were tested. There was poor correlation between HI and EIA in detecting mumps antibodies with correlation coefficient values (r) = 0.190 (P < 0.001), but in rubella antibodies HI and EIA were relatively well correlated (r = 0.930, P < 0.001). Seropositivity rate of HI versus EIA was found to be 65.7 versus 93.2, and 89.5 versus 86.5% for mumps and rubella, respectively. As compared with EIA, HI identified sixfold larger seronegative subjects in mumps. Moreover, in mumps, 88.8% of seronegative subjects detected by HI were seropositive by EIA, while 3.7% of seropositive subjects detected by HI were seronegative by EIA. In rubella, 2.1% of seronegative subjects detected by HI were seropositive by EIA, and 1.7% of seropositive by HI was seronegative by EIA. CONCLUSION: Considerable difference between HI and EIA in determining immune status of health care personnel to mumps and rubella suggests beneficial use of EIA for the identification of accurate susceptible personnel who subsequently undergo an effective vaccination programs. Seroprevalence survey of health care personnel by using appropriate assay is essential for prevention and infection control strategies in health care settings.

Prevalence of hepatitis A antibodies in Eastern Bolivia: a population-based study.

The seroprevalence of hepatitis A virus (HAV) is changing from high to intermediate endemicity in several Latin American countries, but the pattern in the Andean Latin American countries is unknown. A seroepidemiological survey (n = 436) of HAV in schoolchildren living in the Cochabamba region of Bolivia was conducted in 2010. A questionnaire was completed by parents to obtain demographic, socio-economic, and housing data, and blood samples were collected. The overall prevalence of HAV IgG was 95.4% (95% CI 93.5-97.4). The prevalence was higher in children aged 5-10 years (97%) and pre-adolescents aged 10-13 years (97.9%). The prevalence was also higher in subjects whose parents had a low level of education (99.4-99.5%), who lived in rural areas (98.7%), lived in municipalities with low urban development (99.1-100%), had water delivered at home from a tanker (99.4%), and spoke Quechua at home (99.5%). The descriptive and bivariate analysis suggested that no change in HAV epidemiology has occurred in Cochabamba.