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1.
J Clin Virol ; 173: 105696, 2024 Aug.
Article En | MEDLINE | ID: mdl-38823291

BACKGROUND: Measles, mumps, and rubella(MMR) vaccination is critical to measles outbreak responses. However, vaccine reactions and detection of measles vaccine RNA in recently immunized persons may complicate case classification especially in those presenting with another respiratory viral illness. We aim to characterize cases of measles vaccine shedding in recently vaccinated children presenting with respiratory viral symptoms. METHODS: Children who were tested with a multiplex respiratory panel <30 days after receiving MMR were identified. Remnant nasopharyngeal(NP) samples were tested for measles vaccine by PCR. Medical records were reviewed for demographics, presenting symptoms, and test results. RESULTS: From January 2022 to March 2023, 127 NP from children who received MMR were tested. Ninety-six NP were collected after the first dose, of which 33(34.4 %) were positive for vaccine RNA. The median interval between MMR and detection was 11.0 days. Thirty-one NP were collected after the second MMR and 1(3.2 %) was positive; time between the vaccination and detection was 18.9 days. Median cycle threshold(Ct) value of the measles PCR for vaccine shedding was significantly higher than median Ct in children with wild-type infection. CONCLUSION: Shedding of measles vaccine RNA is not uncommon and vaccine RNA can be detected up to 29 days post MMR; the amount of vaccine RNA shedding is low indicated by high Ct values. Clinicians and public health officials should consider performing measles vaccine testing on those testing positive for measles within one month of MMR vaccination, especially if the Ct value is high and definitive epidemiological links are absent.


Measles-Mumps-Rubella Vaccine , RNA, Viral , Vaccination , Virus Shedding , Humans , Measles-Mumps-Rubella Vaccine/administration & dosage , Measles-Mumps-Rubella Vaccine/immunology , Female , Male , RNA, Viral/genetics , Child, Preschool , Infant , Child , Measles/prevention & control , Measles/immunology , Nasopharynx/virology , Mumps/prevention & control , Mumps/immunology , Rubella/prevention & control , Adolescent
2.
Bull Math Biol ; 86(7): 85, 2024 Jun 09.
Article En | MEDLINE | ID: mdl-38853189

How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.


Macaca fascicularis , Mathematical Concepts , Measles virus , Measles , Viral Load , Viremia , Measles/immunology , Measles/transmission , Measles/prevention & control , Measles/virology , Measles/epidemiology , Animals , Viremia/immunology , Viremia/virology , Measles virus/immunology , Measles virus/pathogenicity , Measles virus/physiology , Likelihood Functions , Humans , Models, Immunological , Models, Biological , T-Lymphocytes/immunology , Lymphocyte Activation
3.
Front Public Health ; 12: 1375151, 2024.
Article En | MEDLINE | ID: mdl-38784578

Introduction: Homeless individuals suffer a high burden of vaccine-preventable infectious diseases. Moreover, they are particularly susceptible to adverse infection outcomes with limited access to the health care system. Data on the seroprevalence of measles, mumps, rubella, and varicella within this cohort are missing. Methods: The seroprevalence of measles, mumps, rubella, and varicella was determined within the homeless population in Germany. Predictors of lacking immune protection were determined using multivariable logistic regression analysis. Results: Homeless individuals in Germany (n = 611) showed a seroprevalence of 88.5% (95% CI: 85.8-91.0) for measles, 83.8% (95% CI: 80.6-86.6) for mumps, 86.1% (95% CI: 83.1-88.7) for rubella, and 95.7% (95% CI 93.8-97.2) for varicella. Measles seroprevalences declined from individuals born in 1965 to individuals born in 1993, with seroprevalences not compatible with a 95% threshold in individuals born after 1980. For mumps, seroprevalences declined from individuals born in 1950 to individuals born in 1984. Here, seroprevalences were not compatible with a 92% threshold for individuals born after 1975. Seronegativity for measles, mumps and rubella was associated with age but not with gender or country of origin. Discussion: Herd immunity for measles and mumps is not achieved in this homeless cohort, while there was sufficient immune protection for rubella and varicella. Declining immune protection rates in younger individuals warrant immunization campaigns also targeting marginalized groups such as homeless individuals. Given that herd immunity thresholds are not reached for individuals born after 1980 for measles, and after 1975 for mumps, vaccination campaigns should prioritize individuals within these age groups.


Chickenpox , Ill-Housed Persons , Measles , Mumps , Rubella , Humans , Male , Female , Mumps/immunology , Mumps/epidemiology , Cross-Sectional Studies , Germany/epidemiology , Ill-Housed Persons/statistics & numerical data , Adult , Measles/epidemiology , Measles/immunology , Rubella/immunology , Rubella/epidemiology , Seroepidemiologic Studies , Middle Aged , Chickenpox/epidemiology , Chickenpox/immunology , Young Adult , Vaccination/statistics & numerical data , Adolescent , Aged
5.
Methods Mol Biol ; 2808: 121-127, 2024.
Article En | MEDLINE | ID: mdl-38743366

During the infection of a host cell by an infectious agent, a series of gene expression changes occurs as a consequence of host-pathogen interactions. Unraveling this complex interplay is the key for understanding of microbial virulence and host response pathways, thus providing the basis for new molecular insights into the mechanisms of pathogenesis and the corresponding immune response. Dual RNA sequencing (dual RNA-seq) has been developed to simultaneously determine pathogen and host transcriptomes enabling both differential and coexpression analyses between the two partners as well as genome characterization in the case of RNA viruses. Here, we provide a detailed laboratory protocol and bioinformatics analysis guidelines for dual RNA-seq experiments focusing on - but not restricted to - measles virus (MeV) as a pathogen of interest. The application of dual RNA-seq technologies in MeV-infected patients can potentially provide valuable information on the structure of the viral RNA genome and on cellular innate immune responses and drive the discovery of new targets for antiviral therapy.


Genome, Viral , Host-Pathogen Interactions , Measles virus , Measles , RNA, Viral , Humans , Measles/virology , Measles/immunology , Measles/genetics , Measles virus/genetics , Measles virus/pathogenicity , RNA, Viral/genetics , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Computational Biology/methods , Sequence Analysis, RNA/methods , RNA-Seq/methods , Transcriptome , Gene Expression Profiling/methods , High-Throughput Nucleotide Sequencing/methods
6.
Methods Mol Biol ; 2808: 209-224, 2024.
Article En | MEDLINE | ID: mdl-38743373

The plaque reduction neutralization test (PRNT) and the enzyme-linked immunosorbent assay (ELISA) are both widely used to assess immunity to infectious diseases such as measles, but they use two different measurement principles: ELISA measures the ability of antibodies to bind to virus components, while the PRNT detects the aptitude of antibodies to prevent the infection of a susceptible cell. As a result, detection of measles virus (MV) neutralizing antibodies is the gold standard for assessing immunity to measles. However, the assay is laborious and requires experience and excellent technical skills. In addition, the result is only available after several days. Therefore, the classical PRNT is not suitable for high-throughput testing. By using an immunocolorimetric assay (ICA) to detect MV-infected cells, the standard PRNT has been developed into a focus reduction neutralization test (FRNT). This assay is faster and has improved specificity. The FRNT described here is extremely useful when immunity to measles virus needs to be assessed in patients with a specific medical condition, such as immunocompromised individuals in whom presumed residual immunity needs to be assessed. The FRNT is not generally recommended for use with large numbers of specimens, such as in a seroprevalence study.


Antibodies, Neutralizing , Antibodies, Viral , Measles virus , Measles , Neutralization Tests , Neutralization Tests/methods , Measles virus/immunology , Measles/immunology , Measles/diagnosis , Measles/virology , Humans , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , Chlorocebus aethiops , Animals , Vero Cells , Viral Plaque Assay/methods , Enzyme-Linked Immunosorbent Assay/methods
7.
Methods Mol Biol ; 2808: 247-264, 2024.
Article En | MEDLINE | ID: mdl-38743375

Measles IgG avidity assays determine the overall strength of molecular binding between measles-specific IgG antibodies and measles virus antigens. Avidity results can distinguish recent from distant measles virus infections. Individuals who are immunologically naïve to measles virus develop low-avidity antibodies upon measles virus infection or first-time vaccination. Within 4-6 months, antibodies mature to high avidity. Measles avidity assays are most useful in the context of measles elimination. In such settings, avidity and epidemiological and clinical information are used to classify measles breakthrough infections for control and surveillance purposes and to assist in case confirmation when other laboratory results are inconclusive or nonexistent. We present a highly accurate end-titer measles avidity assay that delivers results based on IgG quality (avidity) that are independent of IgG concentration.


Antibodies, Viral , Antibody Affinity , Immunoglobulin G , Measles virus , Measles , Antibody Affinity/immunology , Immunoglobulin G/immunology , Humans , Antibodies, Viral/immunology , Measles virus/immunology , Measles/immunology , Measles/virology , Antigens, Viral/immunology , Enzyme-Linked Immunosorbent Assay/methods
8.
Methods Mol Biol ; 2808: 225-246, 2024.
Article En | MEDLINE | ID: mdl-38743374

There is increasing interest in evaluating antibody responses to multiple antigen targets in a single assay. Immunity to measles and rubella are often evaluated together because immunity is provided through combined vaccines and because routine immunization efforts and surveillance for measles and rubella pathogens are combined in many countries. The multiplex bead assay (MBA) also known as the multiplex immunoassay (MIA) described here combines the measurement of measles- and rubella-specific IgG antibodies in serum quantitatively according to international serum standards and has been successfully utilized in integrated serological surveillance.


Antibodies, Viral , Immunoglobulin G , Measles , Rubella , Rubella/immunology , Rubella/epidemiology , Rubella/diagnosis , Rubella/blood , Measles/immunology , Measles/epidemiology , Measles/blood , Measles/diagnosis , Humans , Antibodies, Viral/blood , Antibodies, Viral/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoassay/methods , Rubella virus/immunology , Measles virus/immunology , Serologic Tests/methods
9.
Eur J Clin Microbiol Infect Dis ; 43(6): 1139-1148, 2024 Jun.
Article En | MEDLINE | ID: mdl-38613705

OBJECTIVES: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. METHODS: A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). RESULTS: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. CONCLUSION: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.


Antibodies, Viral , Chickenpox , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Luminescent Measurements , Measles virus , Measles , Humans , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Measles/diagnosis , Measles/immunology , Antibodies, Viral/blood , Antibodies, Viral/cerebrospinal fluid , Luminescent Measurements/methods , Enzyme-Linked Immunosorbent Assay/methods , Child , Male , Female , Adult , Adolescent , Chickenpox/diagnosis , Chickenpox/immunology , Measles virus/immunology , Child, Preschool , Young Adult , Middle Aged , Herpesvirus 3, Human/immunology , Sensitivity and Specificity , Infant , Aged , Immunoassay/methods , Reagent Kits, Diagnostic/standards
10.
Int J Infect Dis ; 144: 107053, 2024 Jul.
Article En | MEDLINE | ID: mdl-38641317

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.


Antibodies, Viral , Immunoglobulin G , Measles , Rubella , Humans , Immunoglobulin G/blood , Measles/epidemiology , Measles/prevention & control , Measles/immunology , Adolescent , Child, Preschool , Child , Rubella/epidemiology , Rubella/immunology , Rubella/prevention & control , Adult , Male , Seroepidemiologic Studies , Female , Young Adult , Infant , Antibodies, Viral/blood , Models, Theoretical , Rubella Vaccine/immunology , Rubella Vaccine/administration & dosage , Rubella virus/immunology , Prevalence , Measles Vaccine/immunology , Measles Vaccine/administration & dosage , Age Factors , Vaccination , Immunization Programs , Rubella Syndrome, Congenital/epidemiology , Rubella Syndrome, Congenital/prevention & control , Rubella Syndrome, Congenital/immunology
11.
Emerg Infect Dis ; 30(5): 926-933, 2024 May.
Article En | MEDLINE | ID: mdl-38579738

We investigated clinically suspected measles cases that had discrepant real-time reverse transcription PCR (rRT-PCR) and measles-specific IgM test results to determine diagnoses. We performed rRT-PCR and measles-specific IgM testing on samples from 541 suspected measles cases. Of the 24 IgM-positive and rRT-PCR--negative cases, 20 were among children who received a measles-containing vaccine within the previous 6 months; most had low IgG relative avidity indexes (RAIs). The other 4 cases were among adults who had an unknown previous measles history, unknown vaccination status, and high RAIs. We detected viral nucleic acid for viruses other than measles in 15 (62.5%) of the 24 cases with discrepant rRT-PCR and IgM test results. Measles vaccination, measles history, and contact history should be considered in suspected measles cases with discrepant rRT-PCR and IgM test results. If in doubt, measles IgG avidity and PCR testing for other febrile exanthematous viruses can help confirm or refute the diagnosis.


Antibodies, Viral , Immunoglobulin M , Measles virus , Measles , Humans , Immunoglobulin M/blood , Measles/diagnosis , Measles/epidemiology , Measles/virology , Measles/immunology , Antibodies, Viral/blood , Japan/epidemiology , Child , Child, Preschool , Measles virus/immunology , Measles virus/genetics , Male , Adult , Female , Infant , Adolescent , Immunoglobulin G/blood , Reverse Transcriptase Polymerase Chain Reaction/methods , Measles Vaccine/immunology , Young Adult , Real-Time Polymerase Chain Reaction/methods
12.
Viruses ; 14(12)2022 11 26.
Article En | MEDLINE | ID: mdl-36560645

The immune system deploys a complex network of cells and signaling pathways to protect host integrity against exogenous threats, including measles virus (MeV). However, throughout its evolutionary path, MeV developed various mechanisms to disrupt and evade immune responses. Despite an available vaccine, MeV remains an important re-emerging pathogen with a continuous increase in prevalence worldwide during the last decade. Considerable knowledge has been accumulated regarding MeV interactions with the innate immune system through two antagonistic aspects: recognition of the virus by cellular sensors and viral ability to inhibit the induction of the interferon cascade. Indeed, while the host could use several innate adaptors to sense MeV infection, the virus is adapted to unsettle defenses by obstructing host cell signaling pathways. Recent works have highlighted a novel aspect of innate immune response directed against MeV unexpectedly involving DNA-related sensing through activation of the cGAS/STING axis, even in the absence of any viral DNA intermediate. In addition, while MeV infection most often causes a mild disease and triggers a lifelong immunity, its tropism for invariant T-cells and memory T and B-cells provokes the elimination of one primary shield and the pre-existing immunity against previously encountered pathogens, known as "immune amnesia".


Immune Evasion , Immunity, Innate , Measles virus , Measles , Humans , Interferons , Measles/immunology , Signal Transduction
13.
Lancet ; 399(10325): 678-690, 2022 02 12.
Article En | MEDLINE | ID: mdl-35093206

Measles is a highly contagious, potentially fatal, but vaccine-preventable disease caused by measles virus. Symptoms include fever, maculopapular rash, and at least one of cough, coryza, or conjunctivitis, although vaccinated individuals can have milder or even no symptoms. Laboratory diagnosis relies largely on the detection of specific IgM antibodies in serum, dried blood spots, or oral fluid, or the detection of viral RNA in throat or nasopharyngeal swabs, urine, or oral fluid. Complications can affect many organs and often include otitis media, laryngotracheobronchitis, pneumonia, stomatitis, and diarrhoea. Neurological complications are uncommon but serious, and can occur during or soon after the acute disease (eg, acute disseminated encephalomyelitis) or months or even years later (eg, measles inclusion body encephalitis and subacute sclerosing panencephalitis). Patient management mainly involves supportive therapy, such as vitamin A supplementation, monitoring for and treatment of secondary bacterial infections with antibiotics, and rehydration in the case of severe diarrhoea. There is no specific antiviral therapy for the treatment of measles, and disease control largely depends on prevention. However, despite the availability of a safe and effective vaccine, measles is still endemic in many countries and causes considerable morbidity and mortality, especially among children in resource-poor settings. The low case numbers reported in 2020, after a worldwide resurgence of measles between 2017 and 2019, have to be interpreted cautiously, owing to the effect of the COVID-19 pandemic on disease surveillance. Disrupted vaccination activities during the pandemic increase the potential for another resurgence of measles in the near future, and effective, timely catch-up vaccination campaigns, strong commitment and leadership, and sufficient resources will be required to mitigate this threat.


COVID-19/epidemiology , Endemic Diseases/prevention & control , Mass Vaccination/organization & administration , Measles Vaccine/administration & dosage , Measles/prevention & control , COVID-19/prevention & control , Communicable Disease Control/organization & administration , Communicable Disease Control/standards , Endemic Diseases/statistics & numerical data , Humans , Mass Vaccination/standards , Mass Vaccination/statistics & numerical data , Measles/epidemiology , Measles/immunology , Measles/virology , Measles virus/immunology , Measles virus/pathogenicity , Pandemics/prevention & control
14.
J Immunol Res ; 2021: 5990417, 2021.
Article En | MEDLINE | ID: mdl-34778466

Mumps is a vaccine-preventable disease caused by the mumps virus, but the incidence of mumps has increased among the children who were vaccinated with one-dose measles-mumps-rubella (MMR) in recent years. In this study, we analyzed the influence of different doses of mumps-containing vaccine (MuCV) against mumps using Cox-proportional hazard model. We collected 909 mumps cases of children who were born from 2006 to 2010 and vaccinated with different doses of MuCV in Quzhou during 2006-2018, which were all clinically diagnosed. Kaplan-Meier survival methods and Cox-proportional hazard model were used to estimate the hazard probabilities. Kaplan-Meier curves showed that the cumulative hazard of male and female has no difference; lower hazards were detected among those who were vaccinated with two-dose MuCV, born in 2006, and infected after supplementary immunization activities (SIA). Cox-proportional hazard regression suggested that onset after SIA, born in 2006, and vaccinated with two-dose MuCV were protective factors against infection even after adjusting for potential confounding effects. Our study showed that it was necessary to revise the diagnostic criteria of mumps and identify RT-PCR as the standard for mumps diagnosis in China. We suggested that routine immunization schedule should introduce two doses of MMR and prevaccination screening should be performed before booster immunization in vaccinated populations.


Measles/immunology , Mumps Vaccine/immunology , Antibodies, Viral/immunology , Child , Child, Preschool , China , Disease Outbreaks/prevention & control , Female , Humans , Immunization Schedule , Incidence , Male , Mumps , Mumps virus/immunology , Proportional Hazards Models , Vaccination/methods
15.
Am J Trop Med Hyg ; 105(6): 1608-1617, 2021 10 04.
Article En | MEDLINE | ID: mdl-34607310

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.


Antibodies, Viral/immunology , Measles/immunology , Rubella/immunology , Vaccine-Preventable Diseases/immunology , Adolescent , Adult , Child , Child, Preschool , Community Health Workers , Community Participation , Female , Humans , Implementation Science , India/epidemiology , Infant , Male , Measles/epidemiology , Middle Aged , Rubella/epidemiology , Seroepidemiologic Studies , Serologic Tests , Specimen Handling , Vaccine-Preventable Diseases/epidemiology , Young Adult
16.
mSphere ; 6(4): e0133020, 2021 08 25.
Article En | MEDLINE | ID: mdl-34259557

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.


Blood Specimen Collection/methods , Blood Specimen Collection/standards , Dried Blood Spot Testing/standards , Measles/diagnosis , Rubella/diagnosis , Adolescent , Adult , Antibodies, Viral/blood , Blood Specimen Collection/instrumentation , Dried Blood Spot Testing/methods , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , India/epidemiology , Measles/epidemiology , Measles/immunology , Middle Aged , Reproducibility of Results , Rubella/epidemiology , Rubella/immunology , Seroepidemiologic Studies , Young Adult
17.
mSphere ; 6(4): e0049021, 2021 08 25.
Article En | MEDLINE | ID: mdl-34259563

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.


Antibodies, Viral/blood , Dried Blood Spot Testing/instrumentation , Dried Blood Spot Testing/standards , Immunoglobulin G/blood , Measles/diagnosis , Reagent Kits, Diagnostic/standards , Adult , Dried Blood Spot Testing/methods , Humans , Measles/blood , Measles/immunology , Rubella/blood , Rubella/diagnosis , Rubella/immunology , Sensitivity and Specificity
18.
JAMA Netw Open ; 4(7): e2118508, 2021 07 01.
Article En | MEDLINE | ID: mdl-34319355

Importance: Although patients with cancer are at an increased risk of infection-related complications, few studies have characterized their vulnerability to measles and mumps. Given the recent outbreaks and increased community vaccine hesitancy, understanding measles and mumps immunity within this population is vital. Objectives: To identify a point prevalence estimate of protective measles and mumps antibodies among ambulatory patients with cancer. Design, Setting, and Participants: In this cross-sectional study, residual clinical plasma samples were obtained from consecutive patients with cancer at Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center in Seattle, Washington, in August 2019. These samples were tested for measles and mumps IgG using a commercial enzyme-linked immunosorbent assay. Patients without cancer were excluded from the analysis. Exposures: Patient age, sex, self-reported race and ethnicity, primary disease, receipt of chemotherapy in the past 30 days before sample collection, hematopoietic cell transplant (HCT) history, and date of most recent intravenous immunoglobulin treatment were abstracted from electronic medical records. Main Outcomes and Measures: Measles and mumps IgG seroprevalence, defined as the proportion of patients with positive antibody test results, was measured overall and among the subgroups. Results: Of the 959 patients included in the analysis, 510 (53%) were male individuals and the mean (SD) age at sample collection was 60 (15) years. Most patients (576 [60%]) had a malignant solid tumor, and 383 patients (40%) had a hematologic malignant neoplasm; 146 patients (15%) had an HCT history. Overall, the seroprevalence of measles antibodies was 0.75 (95% CI, 0.72-0.78), and the seroprevalence of mumps antibodies was 0.62 (95% CI, 0.59-0.65). The lowest seroprevalences were among patients with a hematologic malignant neoplasm (0.63 for measles and 0.48 for mumps), those with a history of HCT (0.46 for measles and 0.29 for mumps), and those aged 30 to 59 years (0.49-0.63 for measles and 0.41-0.58 for mumps). Conclusions and Relevance: In this study, 25% of ambulatory patients with cancer lacked protective antibodies for measles and 38% lacked protective antibodies for mumps. Deficits in protective antibodies underscore patients' increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population.


Antibodies, Viral/blood , Immunoglobulin G/blood , Measles/immunology , Mumps/immunology , Neoplasms/blood , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Neoplasms/immunology , Seroepidemiologic Studies
19.
Turk J Med Sci ; 51(5): 2311-2317, 2021 10 21.
Article En | MEDLINE | ID: mdl-33984893

Background/aim: HIV infection increase the risk of serious disease resulting from common vaccine-preventable infections. Vaccinations are particularly important for HIV infected adults. We aimed to investigate the immunity rates against measles, mumps, rubella, hepatitis A, B, and tetanus in newly diagnosed HIV patients. Materials and methods: Patients who admitted to outpatient clinics of three centers with newly diagnosed HIV infection, between 1 January 2015 and 31 June 2017 were included. Measles, mumps, rubella, varicella zoster virus, hepatitis A, hepatitis B, and tetanus antibody levels were measured by commercial diagnostic kits. Demographical and laboratory data of the patients were recorded. Results: Five hundred and twenty-three patients were enrolled in the study. Of the patients 87% were male (n = 455) and the mean age was 38 ± 13 years. Serology was available for measles 74.2% (388/523), mumps 73.8% (386/523), rubella 77.8% (407/523), hepatitis A 88.5% (463/523), hepatitis B 97.7% (511/523), tetanus 8.6% (45/523), and VZV 79.9% (418/523). Seropositivity was 82% for measles, 75.6% for mumps, 92.1% for rubella. Of the patients whom all three of the components of the MMR vaccine was tested, 37.7% (127/337) were susceptible at least one and needed the vaccine. Mean age was lower in patients who are nonimmune to measles and mumps (p = 0.008). Younger patients were also nonimmune for hepatitis A, while older patients were nonimmune for hepatitis B. Conclusion: In our study we found that rates of nonimmunity can increase up to one third of the patients even though there is a national vaccination program. Nonimmune individuals should be detected and vaccinated in line with recent guidelines and response should be monitored because of the possibility of impaired immunity and possible suboptimal response. National campaigns can be launched for adult immunization and physicians should be aware of the importance of adult immunization.


HIV Infections/prevention & control , Measles/immunology , Mumps/immunology , Rubella/immunology , Vaccine-Preventable Diseases/prevention & control , Adult , Female , HIV Infections/epidemiology , Hepatitis A , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Humans , Male , Measles/epidemiology , Measles/prevention & control , Measles-Mumps-Rubella Vaccine , Middle Aged , Mumps/epidemiology , Mumps/prevention & control , Rubella/epidemiology , Rubella/prevention & control , Tetanus/immunology , Tetanus/prevention & control , Vaccination
20.
Am J Trop Med Hyg ; 104(6): 2229-2232, 2021 05 03.
Article En | MEDLINE | ID: mdl-33939639

Zambia conducted a measles and rubella (MR) vaccination campaign targeting children 9 months to younger than 15 years of age in 2016. This campaign was the first introduction of a rubella-containing vaccine in Zambia. To evaluate the impact of the campaign, we compared the MR seroprevalence estimates from serosurveys conducted before and after the campaign in Southern Province, Zambia. The measles seroprevalence increased from 77.8% (95% confidence interval [CI], 73.2-81.9) to 96.4% (95% CI, 91.7-98.5) among children younger than 15 years. The rubella seroprevalence increased from 51.3% (95% CI, 45.6-57.0) to 98.3% (95% CI, 95.5-99.4). After the campaign, slightly lower seroprevalence remained for young adults 15 to 19 years old, who were not included in the campaign because of their age. These serosurveys highlighted the significant impact of the vaccination campaign and identified immunity gaps for those beyond the targeted vaccination age. Continued monitoring of population immunity can signal the need for future targeted vaccination strategies.


Antibodies, Viral/blood , Immunization Programs , Measles Vaccine/administration & dosage , Measles/prevention & control , Rubella Vaccine/administration & dosage , Rubella/prevention & control , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Immunization Programs/standards , Immunization Programs/statistics & numerical data , Infant , Infant, Newborn , Male , Measles/epidemiology , Measles/immunology , Middle Aged , Rubella/epidemiology , Rubella/immunology , Seroepidemiologic Studies , Vaccination/statistics & numerical data , Young Adult , Zambia/epidemiology
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