Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in US infants.

BACKGROUND: As of June 2023, two pneumococcal conjugate vaccines, 20- (PCV20) and 15- (PCV15) valent formulations, are recommended for US infants under a 3 + 1 schedule. This study evaluated the health and economic impact of vaccinating US infants with a new expanded valency PCV20 formulation. METHODS: A population-based, multi cohort, decision-analytic Markov model was developed to estimate the public health impact and cost-effectiveness of PCV20 from both societal and healthcare system perspectives over 10 years. Epidemiological data were based on published studies and unpublished Active Bacterial Core Surveillance System (ABCs) data. Vaccine effectiveness was based on PCV13 effectiveness and PCV7 efficacy studies. Indirect impact was based on observational studies. Costs and disutilities were based on published data. PCV20 was compared to both PCV13 and PCV15 in separate scenarios. RESULTS: Replacing PCV13 with PCV20 in infants has the potential to avert over 55,000 invasive pneumococcal disease (IPD) cases, 2.5 million pneumonia cases, 5.4 million otitis media (OM) cases, and 19,000 deaths across all ages over a 10-year time horizon, corresponding to net gains of 515,000 life years and 271,000 QALYs. Acquisition costs of PCV20 were offset by monetary savings from averted cases resulting in net savings of $20.6 billion. The same trend was observed when comparing PCV20 versus PCV15, with a net gain of 146,000 QALYs and $9.9 billion in net savings. A large proportion of the avoided costs and cases were attributable to indirect effects in unvaccinated adults and elderly. From a health-care perspective, PCV20 was also the dominant strategy compared to both PCV13 and PCV15. CONCLUSIONS: Infant vaccination with PCV20 is estimated to further reduce pneumococcal disease and associated healthcare system and societal costs compared to both PCV13 and PCV15.

Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine.

Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.

Measles immunity gaps among children and adolescents with HIV in Zambia despite high measles vaccination and antiretroviral therapy coverage.

OBJECTIVE: The study objective was to identify measles and rubella immunity gaps among people with HIV (PWH) in Zambia despite high measles vaccine coverage and widespread access to antiretroviral therapy. DESIGN: Nationally representative cross-sectional serosurvey using biorepository specimens. METHODS: Blood specimens collected in the Zambia Population HIV Impact Assessment survey (ZAMPHIA) of 2016 were tested for measles and rubella immunoglobulin G (IgG) antibodies by enzyme immunoassay. Hierarchical generalized additive models were fit to characterize age-specific measles and rubella seroprevalence profiles by HIV infection status. Log-binomial regression was performed to identify factors associated with seronegativity. RESULTS: Of the 25 383 specimens, a subsample of 11 500 were selected and 9852 (85%) were successfully tested. Measles seroprevalence was lower among PWH compared with HIV-uninfected individuals until approximately 30 years of age. Among children younger than the age of 10 years, measles seroprevalence was 47.2% [95% confidence interval (CI): 32.7, 61.7] in PWH and 76.4% (95% CI: 74.9, 78.0) in HIV-uninfected children in same age category. In contrast, rubella seroprevalence was higher among PWH than HIV-uninfected individuals, particularly for children younger than 10 years (68.6% vs. 44.3%, P  < 0.001). Having a detectable viral load was associated with being measles seronegative (adjusted prevalence ratio 0.15, 95% CI: 0.06, 0.38). CONCLUSIONS: These results from a nationally representative serosurvey demonstrate persistence of measles immunity gaps among PWH younger than 30 years of age. There is need to implement the World Health Organization's recommendation to revaccinate children living with HIV against measles following immune reconstitution with antiretroviral therapy to protect these children and prevent measles outbreaks.

An evaluation of the early impact of the COVID-19 pandemic on Zambia's routine immunization program.

Implications of the COVID-19 pandemic for both populations and healthcare systems are vast. In addition to morbidity and mortality from COVID-19, the pandemic also disrupted local health systems, including reductions or delays in routine vaccination services and catch-up vaccination campaigns. These disruptions could lead to outbreaks of other infectious diseases that result in an additional burden of disease and strain on the healthcare system. We evaluated the impact of the COVID-19 pandemic on Zambia's routine childhood immunization program in 2020 using multiple sources of data. We relied on administrative vaccination data and Zambia's 2018 Demographic and Health Survey to project national disruptions to district-specific routine childhood vaccination coverage within the pandemic year 2020. Next, we leveraged a 2016 population-based serological survey to predict age-specific measles seroprevalence and assessed the impact of changes in vaccination coverage on measles outbreak risk in each district. We found minor disruptions to routine administration of measles-rubella and pentavalent vaccines in 2020. This was in part due to Zambia's Child Health Week held in June of 2020 which helped to reach children missed during the first six months of the year. We estimated that the two-month delay in a measles-rubella vaccination campaign, originally planned for September of 2020 but conducted in November of 2020 as a result of the pandemic, had little impact on modeled district-specific measles outbreak risks. This study estimated minimal increases in the number of children missed by vaccination services in Zambia during 2020. However, the ongoing SARS-CoV-2 transmission since our analysis concluded means efforts to maintain routine immunization services and minimize the risk of measles outbreaks will continue to be critical. The methodological framework developed in this analysis relied on routinely collected data to estimate disruptions of the COVID-19 pandemic to national routine vaccination program performance and its impact on children missed at the subnational level can be deployed in other countries or for other vaccines.

Comparison of measles IgG enzyme immunoassays (EIA) versus plaque reduction neutralization test (PRNT) for measuring measles serostatus: a systematic review of head-to-head analyses of measles IgG EIA and PRNT.

BACKGROUND: As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is finding a feasible, accurate, cost-effective, and high throughput assay to measure measles antibody concentrations and estimate susceptibility in a population. We conducted a systematic review to assess, characterize, and - to the extent possible - quantify the performance of measles IgG enzyme-linked assays (EIAs) compared to the gold standard, plaque reduction neutralization tests (PRNT). METHODS: We followed the PRISMA statement for a systematic literature search and methods for conducting and reporting systematic reviews and meta-analyses recommended by the Cochrane Screening and Diagnostic Tests Methods Group. We identified studies through PubMed and Embase electronic databases and included serologic studies detecting measles virus IgG antibodies among participants of any age from the same source population that reported an index (any EIA or multiple bead-based assays, MBA) and reference test (PRNT) using sera, whole blood, or plasma. Measures of diagnostic accuracy with 95% confidence intervals (CI) were abstracted for each study result, where reported. RESULTS: We identified 550 unique publications and identified 36 eligible studies for analysis. We classified studies as high, medium, or low quality; results from high quality studies are reported. Because most high quality studies used the Siemens Enzygnost EIA kit, we generate individual and pooled diagnostic accuracy estimates for this assay separately. Median sensitivity of the Enzygnost EIA was 92.1% [IQR = 82.3, 95.7]; median specificity was 96.9 [93.0, 100.0]. Pooled sensitivity and specificity from studies using the Enzygnost kit were 91.6 (95%CI: 80.7,96.6) and 96.0 (95%CI: 90.9,98.3), respectively. The sensitivity of all other EIA kits across high quality studies ranged from 0% to 98.9% with median (IQR) = 90.6 [86.6, 95.2]; specificity ranged from 58.8% to 100.0% with median (IQR) = 100.0 [88.7, 100.0]. CONCLUSIONS: Evidence on the diagnostic accuracy of currently available measles IgG EIAs is variable, insufficient, and may not be fit for purpose for serosurveillance goals. Additional studies evaluating the diagnostic accuracy of measles EIAs, including MBAs, should be conducted among diverse populations and settings (e.g., vaccination status, elimination/endemic status, age groups).

Historical Population-Level Impact of Infant 13-Valent Pneumococcal Conjugate Vaccine (PCV13) National Immunization Programs on Invasive Pneumococcal Disease in Australia, Canada, England and Wales, Israel, and the United States.

INTRODUCTION: This study estimates the annual population-level impact of 13-valent pneumococcal conjugate vaccine (PCV13) infant national immunization programs (NIPs) on vaccine-type and non-vaccine type invasive pneumococcal disease (IPD) incidence across all ages using national surveillance data. METHODS: We identified countries (Australia, Canada, England and Wales, Israel, and the US) with national IPD active surveillance data that introduced the seven-valent PCV (PCV7) followed by PCV13, which also reported annual serotype- and age group-specific incidence. We extracted IPD incidence by serotype groupings [PCV13 minus PCV7 (PCV13-7) serotypes; PCV13-7 serotypes excluding serotype 3; non-PCV13 serotypes; and the 20-valent (PCV20) minus PCV13 (PCV20-13) serotypes] and by age groups (< 2 years, 2-4 years, 5-17 years, 18-34 years, 35-49 years, 50-64 years, and ≥ 65 years). For each country, we calculated the annual relative change in IPD incidence (percent change), and the corresponding incidence rate ratio (IRR), for 7 years post introduction compared to the year prior to PCV13 program initiation. RESULTS: PCV13-7 vaccine-type IPD incidence consistently decreased over time following introduction of PCV13 across countries, reaching an approximate steady state after 3-4 years in ages < 5 years, with roughly 60-90% decrease (IRRs = 0.1-0.4) and after 4-5 years in ages ≥ 65 years with approximately 60-80% decrease (IRRs = 0.2-0.4). Incidence declines were more substantial for the PCV13-7 grouping when excluding serotype 3. Non-PCV13 serotype incidence was variable by country and age group, ranging from virtually no serotype replacement compared to the PCV7 period across ages in the US to increases for other countries ranging from 10 to 204% (IRRs = 1.10-3.04) in children < 5 years and 41% to 123% (IRRs = 1.41-2.23) in ages ≥ 65 years. CONCLUSIONS: Countries with longstanding PCV13 infant NIPs have observed substantial direct and indirect benefits, which are demonstrated in this study by the reduction in PCV13-7 IPD incidence compared to PCV7 period in all age groups. Over time, non-PCV13 serotypes have emerged in response to the reduction of incidence of PCV13-unique serotypes. Higher-valent PCVs are needed to address this emerging pneumococcal disease burden as well as the direct vaccination of both pediatric and adult populations against the most prevalent circulating serotypes.

Acceptability of serosurveys in southern Zambia: data collector and caregiver perspectives.

Background: Factors associated with whether individuals choose to participate in serosurveys are not well understood. Understanding perceptions from multiple perspectives, including the perspectives of both data collectors and participants, through a holistic model such as the socio-ecological model contextualizes individual, interpersonal, and structural level influences on survey research participation. We used a multiple methods approach to characterize reasons for serosurvey participation in communities in Southern Province, Zambia where a serosurvey was conducted in 2016. Methods: The first phase conducted focus group discussions and in-depth interviews with 24 data collectors who participated in a measles-rubella serosurvey in 2016. The second phase surveyed 34 caregivers at health facilities to identify barriers and facilitators to serosurvey participation. Emergent themes were then classified into a socio-ecological model using individual, interpersonal, and structural level constructs. Results: Common themes emerged from data collectors as well as caregivers surveyed. At the individual level, providing incentives was a facilitator, and some religious beliefs were described as a barrier to serosurvey participation. At the interpersonal level, family dynamics and community peer influences could help or hinder serosurvey participation. Community health workers were consistently named as facilitators of participation. At the structural level, concerns about specimen collection, who was selected for serosurveys, and not receiving test results arose as potential barriers. The most frequently reported facilitator was provision of information about the purpose of the serosurvey (85% of respondents). The most frequently reported barrier was lack of clarity regarding use of their blood specimen (53% of respondents). For specimen collection type, caregivers consistently preferred finger prick blood collection over both venous blood draw and oral swabs. Conclusion: Serosurvey participation was deemed acceptable to most study participants. The socio-ecological model revealed barriers and facilitators for participation to guide strategies to improve participation which can be applied to ongoing serosurveys for SARS-CoV-2. Serosurveys should continue to develop engagement plans to provide information about blood collection ahead of the serosurvey and communicate the objectives of such studies through trusted sources such as community health workers and traditional leaders.

Evaluating the effect of measles and rubella mass vaccination campaigns on seroprevalence in India: a before-and-after cross-sectional household serosurvey in four districts, 2018-2020.

BACKGROUND: India did phased measles-rubella supplementary immunisation activities (MR-SIAs; ie, mass-immunisation campaigns) targeting children aged 9 months to less than 15 years. We estimated measles-rubella seroprevalence before and after the MR-SIAs to quantify the effect on population immunity and identify remaining immunity gaps. METHODS: Between March 9, 2018 and March 19, 2020 we did community-based, cross-sectional serosurveys in four districts in India before and after MR-SIAs. 30 villages or wards were selected within each district, and one census enumeration block from each was selected as the survey cluster. Households were enumerated and 13 children in the younger age group (9 months to <5 years) and 13 children in the older ager group (5 to <15 years) were randomly selected by use of computer-generated random numbers. Serum samples were tested for IgG antibodies to measles and rubella viruses by enzyme immunoassay. FINDINGS: Specimens were collected from 2570 children before the MR-SIA and from 2619 children afterwards. The weighted MR-SIA coverage ranged from 73·7% to 90·5% in younger children and from 73·6% to 93·6% in older children. Before the MR-SIA, district-level measles seroprevalence was between 80·7% and 88·5% among younger children in all districts, and between 63·4% and 84·5% among older children. After the MR-SIA, measles seroprevalence among younger children increased to more than 90% (range 91·5 to 96·0) in all districts except Kanpur Nagar, in which it remained unchanged 80·4%. Among older children, measles seroprevalence increased to more than 90·0% (range 93·7% to 96·5%) in all districts except Hoshiarpur (88·7%). A significant increase in rubella seroprevalence was observed in all districts in both age groups, with the largest effect in Dibrugarh, where rubella seroprevalence increased from 10·6% to 96·5% among younger children. INTERPRETATION: Measles-rubella seroprevalence increased substantially after the MR-SIAs but the serosurvey also identified remaining gaps in population immunity. FUNDING: The Bill & Melinda Gates Foundation and Indian Council of Medical Research.

Building an integrated serosurveillance platform to inform public health interventions: Insights from an experts' meeting on serum biomarkers.

The use of biomarkers to measure immune responses in serum is crucial for understanding population-level exposure and susceptibility to human pathogens. Advances in sample collection, multiplex testing, and computational modeling are transforming serosurveillance into a powerful tool for public health program design and response to infectious threats. In July 2018, 70 scientists from 16 countries met to perform a landscape analysis of approaches that support an integrated serosurveillance platform, including the consideration of issues for successful implementation. Here, we summarize the group's insights and proposed roadmap for implementation, including objectives, technical requirements, ethical issues, logistical considerations, and monitoring and evaluation.

Experiences of sharing results of community based serosurvey with participants in a district of Maharashtra, India.

A growing number of organisations, including medical associations, recommend that research subjects should be given the option of being informed about the general outcome and results of the study. We recently completed a study involving nine serosurveys from 2018 to 2020 in five districts of India among three age groups (children 9 months to < 5 years; 5 to < 15 years of age, and women 15 to < 50 years of age before and after the measles and rubella (MR) vaccination campaigns). In Palghar district of Maharashtra all individuals in 30 selected clusters were enumerated, and 13 individuals per age group were randomly sampled. We established the procedures to return the results to the respondents for each stage of the survey. Of the 1,166 individuals selected for the measles and rubella serosurvey, 971 (83%) agreed to participate and were enrolled. Participants were informed that they will only be contacted if they test seronegative for measles and/or rubella antibodies. Overall, 140 individuals enrolled in the survey tested seronegative for IgG antibodies to measles and/or rubella viruses; were provided the reports and informed to seek medical advice. Upon follow up by phone, 10% (14) of the 140 participants reported to have been vaccinated. In this paper we discuss the procedures, experiences and considerations in returning results to participants in a community-based measles and rubella serosurvey. Although the lessons learned are specific to post measles-rubella vaccine campaign serosurvey in India, they might be helpful to those contemplating sharing results to participants of large scale survey settings.

Leveraging a national biorepository in Zambia to assess measles and rubella immunity gaps across age and space.

High-quality, representative serological surveys allow direct estimates of immunity profiles to inform vaccination strategies but can be costly and logistically challenging. Leveraging residual serum samples is one way to increase their feasibility. We subsampled 9854 residual sera from a 2016 national HIV survey in Zambia and tested these specimens for anti-measles and anti-rubella virus IgG antibodies using indirect enzyme immunoassays. We demonstrate innovative methods for sampling residual sera and analyzing seroprevalence data, as well as the value of seroprevalence estimates to understand and control measles and rubella. National measles and rubella seroprevalence for individuals younger than 50 years was 82.8% (95% CI 81.6, 83.9%) and 74.9% (95% CI 73.7, 76.0%), respectively. Despite a successful childhood vaccination program, measles immunity gaps persisted across age groups and districts, indicating the need for additional activities to complement routine immunization. Prior to vaccine introduction, we estimated a rubella burden of 96 congenital rubella syndrome cases per 100,000 live births. Residual samples from large-scale surveys can reduce the cost and challenges of conducting serosurveys, and multiple pathogens can be tested. Procedures to access quality specimens, ensure ethical approvals, and link sociodemographic data can improve the timeliness and value of results.

The broader impacts of otitis media and sequelae for informing economic evaluations of pneumococcal conjugate vaccines.

INTRODUCTION: Otitis media (OM) is a common childhood infection. Pneumococcal conjugate vaccines (PCVs) prevent OM episodes, thereby reducing short- and long-term clinical, economic, humanistic, and societal consequences. Most economic evaluations of PCVs focus on direct health gains and cost savings from prevented acute episodes but do not fully account for the broader societal impacts of OM prevention. AREAS COVERED: This review explores the broader burden of OM on children, caregivers, and society to better inform future economic evaluations of PCVs. EXPERT OPINION: OM causes a substantial burden to society through long-term sequelae, productivity losses, reduced quality of life for children and caregivers, and contribution to antimicrobial resistance from inappropriate antibiotic use. The effect of PCVs on acute OM has been recognized globally, yet the broader impact has not been consistently quantified, studied, or communicated. Economic evaluations of PCVs must evolve to include broader effects for patients, caregivers, and society from OM prevention. Future PCVs with broader coverage may further reduce OM incidence and antimicrobial resistance, but optimal uptake will depend on increasing the recognition and use of novel frameworks that include broader benefits. Communicating the full value of PCVs to decision makers may result in wider access and positive societal returns.

Diagnostic accuracy of dried blood spots for serology of vaccine-preventable diseases: a systematic review.

INTRODUCTION: Venous serum and plasma are optimal specimens for serological testing but may be logistically infeasible. Dried blood spots (DBS) are a feasible alternative, provided results are adequately sensitive and specific. We aimed to assess the diagnostic accuracy of DBS to measure IgG and IgM antibodies for vaccine-preventable diseases and compare test validity of DBS with venous blood. AREAS COVERED: In October 2020, we searched seven databases for peer-reviewed studies assessing the diagnostic accuracy of DBS specimens compared with serum in detecting antibodies to VPDs in humans. We extracted data and assessed risk of bias in all included studies. We calculated sensitivity and specificity with 95% confidence intervals for each index-reference test comparison. We narratively synthesized the identified evidence on diagnostic accuracy and blood collection and processing methods for DBS. Studies on measles and rubella IgG and IgM were the most frequently identified and reported generally high sensitivity and specificity. EXPERT OPINION: Lack of standardization in collection, storage, and testing methods limited systematic comparison across studies. Our findings indicate a need for additional validation studies on the diagnostic accuracy of DBS to expand their use in serological surveillance. We recommend practical considerations to improve standardized reporting for DBS validation studies.

Clinical and Economic Burden of Pneumococcal Disease Due to Serotypes Contained in Current and Investigational Pneumococcal Conjugate Vaccines in Children Under Five Years of Age.

INTRODUCTION: The widespread implementation of pneumococcal conjugate vaccines (PCVs) has significantly reduced the burden of pneumococcal disease around the world. Although licensed 10-valent (PCV10) and 13-valent (PCV13) vaccines have considerably reduced mortality and morbidity, a sizeable disease burden attributable to serotypes not contained in these PCVs remains. This study aimed to estimate the annual clinical and economic burden of pneumococcal disease attributable to licensed (PCV10 and PCV13) and investigational PCVs, notably 15-valent (PCV15) and 20-valent (PCV20) vaccines, in 13 countries in children under 5 years of age. METHODS: A decision-analytic model was created to aggregate total cases [inclusive of invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM)], deaths, and direct costs in each country of interest [stratified by PCV10/PCV13 countries, depending on national immunization programs (NIPs)] over 1 year, using up to the three most recent years of available serotype coverage data. Data inputs were sourced from local databases, surveillance reports, and published literature. RESULTS: In 5 PCV10 NIPs (Austria, Finland, Netherlands, New Zealand, Sweden), most remaining PCV20-type disease was due to PCV13-unique serotypes (30-85%), followed by PCV20-unique (9-50%), PCV15-unique (4-15%), and PCV10-unique (2-14%) serotypes. In 8 PCV13 NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, United Kingdom), most remaining PCV20-type disease was caused by PCV20-unique serotypes (16-69%), followed by PCV13-unique (11-54%), PCV15-unique (2-33%), and PCV10-unique serotypes (3-19%). Across all countries, PCV20 serotypes caused 3000 to 345,000 cases of disease and cost between $1.3 and $44.9 million USD annually with variability driven by population size, NIP status, and epidemiologic inputs. In aggregate, PCV20 serotypes caused 1,234,000 cases and $213.5 million in annual direct medical costs in children under 5 years of age. CONCLUSION: Despite the success of PCV10 and PCV13 in reducing pneumococcal disease, a substantial clinical and economic burden remains due to serotypes contained in investigational vaccines.

Plasma concentrations of leptin at mid-pregnancy are associated with gestational weight gain among pregnant women in Tanzania: a prospective cohort study.

BACKGROUND: Gestational weight gain (GWG) has critical implications for maternal and child health. Inflammation and angiogenesis are implicated in various aspects of maternal metabolism that may play a role in gestational weight gain. The associations of inflammatory, angiogenic, and metabolic pathways with GWG are yet to be elucidated. This study evaluated associations between a panel of inflammatory, angiogenic, and metabolic proteins measured in mid-pregnancy and gestational weight gain. METHODS: Pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. The participants were enrolled at mid-pregnancy (12 to 27 weeks of gestation) and followed up until delivery. This analysis focused on a cohort of 1002 women who were primigravid, had singleton live births, had longitudinal measures of gestational weight, and whose mid-pregnancy plasma samples underwent analysis for 18 proteins. RESULTS: Higher plasma concentrations of leptin (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 10.24; 95% CI 3.31, 17.16; p-trend = 0.003) and chitinase-3-like protein-1 (CH3L1) (mean difference in GWG percent adequacy comparing highest with lowest quartiles: 7.02; 95% CI 0.31, 13.72; p-trend = 0.007) were associated with greater GWG in a dose-response pattern. Higher leptin concentrations were associated with a lower risk of inadequate GWG (risk ratio comparing highest with lowest quartiles: 0.77; 95% CI 0.65, 0.91; p-trend = 0.001) and a higher risk of excessive GWG (risk ratio comparing highest with lowest quartiles: 1.57; 95% CI 1.03, 2.39; p-trend = 0.03). Higher CH3L1 concentrations were associated with a higher risk of excessive GWG (p-trend = 0.007). The associations of leptin and CH3L1 with inadequate GWG were stronger during the second than the third trimester. The other 16 proteins examined were not significantly associated with GWG. CONCLUSIONS: Mid-pregnancy plasma leptin concentrations may be associated with GWG and have clinical predictive utility in identifying women at a higher risk of inadequate or excessive gestational weight gain.

Implementing Serosurveys in India: Experiences, Lessons Learned, and Recommendations.

Serological surveillance for vaccine-preventable diseases, such as measles and rubella, can provide direct measures of population immunity across age groups, identify gaps in immunity, and document changes in immunity over time. Rigorously conducted, representative household serosurveys provide high-quality estimates with minimal bias. However, they can be logistically challenging, expensive, and have higher refusal rates than vaccine coverage surveys. This article shares lessons learned through implementing nine measles and rubella household serosurveys in five districts in India-the challenges faced, the potential impact on results, and recommendations to facilitate the conduct of serosurveys. Specific lessons learned arose from challenges related to community mobilization owing to lack of cooperation in certain settings and populations, limitations of outdated census information, nonresponse due to refusal or unavailability during survey enumeration and enrollment, data collection issues, and specimen collection and handling issues. Although some experiences are specific to serosurveys in India, these lessons are generalizable to other household surveys, particularly vaccination coverage and serosurveys conducted in low- and middle-income settings.

Diagnostic Accuracy of Dried Blood Spots Collected on HemaSpot HF Devices Compared to Venous Blood Specimens To Estimate Measles and Rubella Seroprevalence.

Fingerprick blood spotted onto filter paper offers an alternative to venous blood for use in population-based surveillance because it is comparatively inexpensive, acceptable, and easy to manage in the field. Prior studies have shown excellent agreement for immunoglobulin G (IgG) antibody detection from dried blood spots (DBS) and venous blood samples. However, much of this evidence is from high-income settings or laboratories where the samples were unlikely to be exposed to extreme temperatures and humidity, factors known to degrade DBS. We report the diagnostic accuracy of DBS collected using HemaSpot HF devices against venous sera in measuring measles- and rubella-specific IgG antibodies in a household serosurvey conducted in two districts in India. Paired serum and DBS samples collected by fingerprick were collected from women aged 15 to 50 years enrolled in a serosurvey in Palghar District of Maharashtra and Kanpur Nagar District of Uttar Pradesh in India. Specimen quality and volume were assessed in the laboratory. Samples were tested for antimeasles and antirubella IgG antibodies by an enzyme-linked immunosorbent assay (ELISA) (Euroimmun). Sensitivity of antibody detection by DBS was greater than 98%, and specificity was 90% and 98%, for measles and rubella IgG, respectively. Antibody concentrations were strongly correlated between paired specimens with adequate volume (measles R2 = 0.94; rubella R2 = 0.89). Although correlation was poor if DBS specimens had lower volumes, impact on qualitative results was minimal. This study showed DBS collected with HemaSpot HF devices can generate highly accurate results of measles- and rubella-specific IgG compared to sera in community-based surveys when protocols are optimized for DBS specimens. IMPORTANCE Dried blood spot (DBS) collection provides an easy, practical, and acceptable alternative to venous blood collection, especially for community-based studies, provided that results from DBS are accurate. We demonstrated high sensitivity and specificity for measles- and rubella-specific immunoglobulin G (IgG) with DBS collected via HemaSpot HF devices compared to serum samples. This is one of the largest community-based diagnostic accuracy studies of measles and rubella antibody testing with DBS and the first application we are aware of using HemaSpot HF device for measles and rubella serology. Results support the use of DBS in community-based serosurveillance.

Optimization and Stability Testing of Four Commercially Available Dried Blood Spot Devices for Estimating Measles and Rubella IgG Antibodies.

Blood collection using dried blood spots (DBS) provides an easier alternative to venipuncture for sample collection, transport, and storage but requires additional processing that can cause variability in results. Whole-blood samples spotted on four DBS devices and respective paired serum samples were tested for antimeasles and antirubella IgG antibody concentrations by enzyme immunoassay. Elution protocols for DBS devices were optimized for comparability relative to serum samples using 12 adult volunteers. Stability of DBS collected on HemaSpot HF was assessed under various temperature conditions (+4, 22 to 25, and 45°C) at six time points (0, 7, 15, 30, 60, and 90 days) in a controlled laboratory setting using six adult volunteers. Devices were shipped and stored for 30 days at four settings with variable temperature and humidity conditions to assess the impact on antibody concentrations. Three DBS devices demonstrated comparable antibody concentrations with paired sera following optimization. Antibodies recovered from DBS were stable for at least 90 days at 4°C and for 30 days at ambient temperature (22 to 25°C) using the HemaSpot HF device. A drastic decline in antibody concentrations was observed at 45°C, resulting in quantitative and qualitative discrepancies by day 7. HemaSpot HF devices shipped to field sites and stored at ambient temperature and humidity resulted in quantitative, but not qualitative, variability. Measurement of antimeasles and antirubella IgG antibodies with DBS devices is an accurate alternative to testing serum, provided elution protocols are optimized. Stability of HemaSpot HF devices at ambient temperature enables broader use in surveys when serum processing and cold storage are not feasible. IMPORTANCE Dried blood spot (DBS) collection offers various advantages over conventional methods of blood collection, especially when collecting and transporting samples for a serosurvey. Yet use of DBS requires additional processing steps in the laboratory that can add to variability in results. We optimized a protocol to elute IgG antibodies against measles and rubella viruses in four DBS devices, demonstrating high concordance with paired venous sera for most devices. Extensive stability studies with various temperature and storage conditions in the laboratory and in the field were conducted using HemaSpot HF DBS devices prior to its use in one of the largest community-based measles and rubella serological surveys in the world.