Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 51 Records) |
Query Trace: Hickman C [original query] |
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Long-term neutralizing antibody levels against measles and rubella viruses among adults with 3 doses of measles-mumps-rubella vaccine
Alonge OD , Marin M , Hickman CJ , Sowers SB , Chen MH , Hao L , Mercader S , El-Badry E , McClure DL , Icenogle JP , Sugerman DE , Crooke SN , Nguyen HQ . Open Forum Infect Dis 2024 11 (1) ofad700 BACKGROUND: A third dose of measles-mumps-rubella vaccine (MMR) may be administered for various reasons, but data on long-term immunity are limited. We assessed neutralizing antibody levels against measles and rubella among adults up to 11 years after receipt of a third MMR dose. METHODS: In this longitudinal study, healthy adults who received a third MMR dose as young adults (ages 18-28 years) were recalled around 5 years and 9-11 years after the third dose. Measles and rubella antibody levels were assessed by plaque-reduction and immunocolorimetric neutralization assays, respectively. Antibody concentrations <120 mIU/mL and <10 U/mL were considered potentially susceptible to measles and rubella, respectively. Geometric mean concentrations (GMCs) and 95% confidence intervals (CIs) over time were estimated from generalized estimating equation models. RESULTS: Approximately 5 and 9-11 years after receipt of the third dose, 405 and 304 adults were assessed, respectively. Measles GMC was 428 mIU/mL (95% CI, 392-468 mIU/mL) 5 years postvaccination, declining to 381 mIU/mL (95% CI, 339-428 mIU/mL) 11 years postvaccination. At the last follow-up visit (9-11 years postvaccination), 10% of participants were potentially susceptible to measles infection. Rubella GMCs were stable throughout the follow-up period (63 U/mL to 65 U/mL); none of the participants was susceptible to rubella at the last follow-up visit. CONCLUSIONS: Eleven years after receiving a third MMR dose, measles and rubella neutralizing antibody levels remained high in adults. However, on the basis of waning antibody levels, some adults may become susceptible to measles infection over time despite receipt of 3 vaccine doses. |
Interim impact evaluation of the hepatitis C virus elimination program in Georgia (preprint)
Walker JG , Fraser H , Lim AG , Gvinjilia L , Hagan L , Kuchuloria T , Martin NK , Nasrullah M , Shadaker S , Aladashvili M , Asatiani A , Baliashvili D , Butsashvili M , Chikovani I , Khonelidze I , Kirtadze I , Kuniholm MH , Otiashvili D , Stvilia K , Tsertsvadze T , Hickman M , Morgan J , Gamkrelidze A , Kvaratskhelia V , Averhoff F , Vickerman P . bioRxiv 2018 270579 Background and Aims Georgia has one of the highest hepatitis C virus (HCV) prevalence rates in the world, with >5% of the adult population (~150,000 people) chronically infected. In April 2015, the Georgian government, in collaboration with CDC and other partners, launched a national program to eliminate HCV through scaling up HCV treatment and prevention interventions, with the aim of achieving a 90% reduction in prevalence by 2020. We evaluate the interim impact of the HCV treatment program as of 31 October 2017, and assess the feasibility of achieving the elimination goal by 2020.Method We developed a dynamic HCV transmission model to capture the current and historical epidemic dynamics of HCV in Georgia, including the main drivers of transmission. Using the 2015 national sero-survey and prior surveys conducted among people who inject drugs (PWID) from 1997-2015, the model was calibrated to data on HCV prevalence by age, gender and PWID status, and the age distribution of PWID. We use the model to project the interim impact of treatment strategies currently being undertaken as part of the ongoing Georgia HCV elimination program, while accounting for treatment failure/loss to follow up, in order to determine whether they are on track to achieving their HCV elimination target by 2020, or whether strategies need to be modified to ensure success.Results A treatment rate of 2,050 patients/month was required from the beginning of the national program to achieve a 90% reduction in prevalence by the end of 2020, with equal treatment rates of PWID and the general population. From May 2015 to October 2017, 40,420 patients were treated, an average of ~1,350 per month; although the treatment rate has recently declined from a peak of 4,500/month in September 2016 to 2100/month in November-December 2016, and 1000/month in August-October 2017, with a sustained virological response rate (SVR) of 98% per-protocol or 78% intent to treat. The model projects that the treatments undertaken up to October 2017 have reduced adult chronic prevalence by 26% (18-35%) to 3.7% (2.9-5.1%), reduced total incidence by 25% (15-35%), and prevented 1845 (751-3969) new infections and 93 (31-177) HCV-related deaths. If the treatment rate of 1000 patients initiated per month continues, prevalence will have halved by 2020, and reduce by 90% by 2026. In order to reach a 90% reduction by 2020, the treatment rate must increase 3.5-fold to 4000/month.Conclusion The Georgia HCV elimination program has accomplished an impressive scale up of treatment, which has already impacted on prevalence and incidence, and averted deaths due to HCV. However, extensive scale up is needed to achieve a 90% reduction in prevalence by 2020. |
Performance Characteristics of Six Immunoglobulin M (IgM) ELISA Assays Used for Laboratory Confirmation of Measles (preprint)
Sowers SB , Anthony K , Mercader S , Colley H , Crooke SN , Rota PA , Latner DR , Hickman CJ . medRxiv 2022 04 Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles specific IgM in serum by enzyme linked immunosorbent assay (ELISA) is the most used method for confirming measles infection. ELISA formats vary as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false negative result, which can delay confirmation of measles cases. Interfering substances can yield a false positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against 5 commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; sensitivity and specificity for the commercial kits ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False positive results occurred in 2.0 to 13.1% of sera while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high quality measles surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Etiological analysis of discarded measles in the context of a measles outbreak among a highly immunized population
Torner N , Mercader S , Dominguez A , Martinez A , Costa J , Sowers SB , Abernathy ES , Bellini WJ , Hickman CJ . Pediatr Int 2022 65 (1) e15430 BACKGROUND: Measles can lead to serious complications and remains an important cause of morbidity and mortality worldwide. We aimed to assess the etiological diagnosis of discarded measles cases in the context of an outbreak among a highly immunized population. METHODS: We conducted a retrospective observational study of discarded measles cases from an outbreak that occurred from October 2006 to July 2007 in Catalonia. A confirmed case was defined as having a positive measles serum IgM result and/or a positive result by RT-PCR in urine and/or nasopharyngeal swab; or an epidemiological link to a confirmed case. Serum specimens were tested by a commercially available indirect-format and by an in-house capture-format measles IgM enzyme immunoassays. RESULTS: Testing of 89 samples discarded for measles determined the etiologies for 10 (11.2%), including 1 rubella, 3 human herpes virus 6, and 6 measles infections. Of 381 confirmed cases in the outbreak, 10% had received at least one dose of the measles-mumps-rubella vaccine versus 54% of the discarded for measles (OR=0.09: 95%CI 0.06, 0.14; p<0.001). CONCLUSIONS: Highly sensitive surveillance systems are critical to identifying cases, responding to outbreaks and verifying progress towards measles elimination. Molecular tools for measles detection and differential diagnosis, and collection of appropriate specimens for molecular and serologic testing are essential to correctly diagnose suspected measles infection. |
Performance characteristics of six immunoglobulin m enzyme-linked immunosorbent assays used for laboratory confirmation of measles
Sowers SB , Anthony K , Mercader S , Colley H , Crooke SN , Rota PA , Latner DR , Hickman CJ . J Clin Microbiol 2022 60 (12) e0122722 Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles-specific IgM in serum by enzyme-linked immunosorbent assay (ELISA) is the most common method used to confirm measles infection. ELISA formats vary, as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false-negative result, which can delay confirmation of measles cases. Interfering substances can yield a false-positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against five commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; the sensitivity and specificity for each commercial kit ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False-positive results occurred in 2.0 to 13.1% of sera, while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high-quality measles surveillance. |
Preservation of lymphocyte functional fitness in perinatally-infected and treated HIV+ pediatric patients displaying sub-optimal viral control
Khanolkar A , Muller WJ , Simpson BM , Cerullo J , Williams R , Sowers SB , Matthews K , Mercader S , Hickman CJ , D'Aquila RT , Liu G . Commun Med (Lond) 2022 2 BACKGROUND: Host-pathogen dynamics associated with HIV infection are quite distinct in children versus adults. We interrogated the functional fitness of the lymphocyte responses in two cohorts of perinatally infected HIV+ pediatric subjects with early anti-retroviral therapy (ART) initiation but divergent patterns of virologic control. We hypothesized that sub-optimal viral control would compromise immune functional fitness. METHODS: The immune responses in the two HIV+ cohorts (n = 6 in each cohort) were benchmarked against the responses measured in age-range matched, uninfected healthy control subjects (n = 11) by utilizing tests for normality, and comparison [the Kruskal-Wallis test, and the two-tailed Mann-Whitney U test (where appropriate)]. Lymphocyte responses were examined by intra-cellular cytokine secretion, degranulation assays as well as phosflow. A subset of these data were further queried by an automated clustering algorithm. Finally, we evaluated the humoral immune responses to four childhood vaccines in all three cohorts. RESULTS: We demonstrate that contrary to expectations pediatric HIV+ patients with sub-optimal viral control display no significant deficits in immune functional fitness. In fact, the patients that display better virologic control lack functional Gag-specific T cell responses and compared to healthy controls they display signaling deficits and an enrichment of mitogen-stimulated CD3 negative and positive lymphocyte clusters with suppressed cytokine production. CONCLUSIONS: These results highlight the immune resilience in HIV+ children on ART with sub-optimal viral control. With respect to HIV+ children on ART with better viral control, our data suggest that this cohort might potentially benefit from targeted interventions that might mitigate cell-mediated immune functional quiescence. |
Classification of measles breakthrough cases in an elimination setting using a comprehensive algorithm of laboratory results: why highly sensitive and specific IgM assays are important
Mercader S , Dominguez A , Torner N , Costa J , Sowers S , Martinez A , Bellini WJ , Hickman CJ . Int J Infect Dis 2021 112 21-24 OBJECTIVE: In 2006, a measles outbreak occurred in Catalonia (Spain), six years after endemic measles was declared eliminated. The aim of this study was to classify 19 confirmed measles breakthrough cases (BC) using a high-performance avidity assay developed in 2010. METHODS: Serum specimens were tested by indirect IgG, indirect IgM, capture IgM enzyme immunoassay, an endpoint-titer IgG avidity assay, and a plaque reduction neutralization assay. Serology and RNA detection results were combined in an algorithm for measles confirmation and classification of breakthrough cases and analyzed with clinical and epidemiological data. RESULTS: Of 19 samples, 13 (68%) were conclusive with classification of BCs and 6 (32%) had false-positive IgM results on an indirect-format assay; they were classified as rash and fever illness of undetermined etiology. BCs were primary vaccine failures (7 or 54%), secondary vaccine failures (4 or 31%) and 2 (15%) could not be classified. CONCLUSIONS: In measles elimination settings, high-performing assays and a comprehensive algorithm of laboratory results (IgG, IgM and RNA detection) including IgG avidity and PRN results, when necessary, can assist in accurate laboratory confirmation and classification of suspected measles cases for surveillance. Highly specific IgM assays are required to minimize the number of false-positive results. |
Measles infection in persons with secondary vaccine failure, New York City, 2018-19
Hickman CJ , Colley H . Vaccine 2021 39 (38) 5346-5350 A large measles outbreak in New York City, which included cases among vaccinated persons and adults presumed to be immune, provided the opportunity to better understand vaccine failure and the potential impact on measles transmission. Immunoglobulin G (IgG) avidity can distinguish primary (low avidity IgG, indicating no evidence of prior immunity) versus secondary vaccine failure (high avidity IgG, indicating prior immune response and waning antibody). Measles IgG avidity was measured on samples from 62 persons: avidity was high in 53 (16 vaccinated and 37 with unknown vaccination history) and low in 9 (1 recently vaccinated and 8 with unknown vaccination history). Secondary transmission from 2 persons with high-avidity IgG results occurred. These findings illustrate that in settings of sustained measles elimination, measles infection and transmission can occur in persons with secondary vaccine failure, underscoring the need to maintain a high index of suspicion for measles during an outbreak despite prior or presumed prior vaccination. |
Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity
Coughlin MM , Matson Z , Sowers SB , Priest JW , Smits GP , van der Klis FRM , Mitchell A , Hickman CJ , Scobie HM , Goodson JL , Alexander JPJr , Rota PA , Bankamp B . J Clin Microbiol 2021 59 (6) Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles whole virus antigen MBA (MeV WVA(L)) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole virus antigen (MeV WVA(C)) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVA(C) and MeV WVA(L) MBAs (R=0.962, R(2)=0.926). IgG concentrations from the MeV WVA(C) MBA showed strong correlation with PRN titers (R=0.846) with a linear relationship comparable to values obtained with the MeV WVA(L) MBA and PRN assay (R(2)=0.716 and R(2)=0.768, respectively). Receiver-operating characteristic (ROC) curve analysis of the MeV WVA(C) using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 84%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R=0.959 and R(2)=0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multi-antigen serosurveys assessing measles and rubella population immunity. |
Functional Characterization of Circulating Mumps Viruses with Stop Codon Mutations in the Small Hydrophobic Protein.
Stinnett RC , Beck AS , Lopareva EN , McNall RJ , Latner DR , Hickman CJ , Rota PA , Bankamp B . mSphere 2020 5 (6) Between 2015 and 2017, routine molecular surveillance in the United States detected multiple mumps viruses (MuVs) with mutations in the small hydrophobic (SH) gene compared to a reference virus of the same genotype. These mutations include an unusual pattern of uracil-to-cytosine hypermutations and other mutations resulting in the generation of premature stop codons or disruption of the canonical stop codon. The mumps virus SH protein may serve as a virulence factor, based on evidence that it inhibits apoptosis and innate immune signaling in vitro and that recombinant viruses that do not express the SH protein are attenuated in an animal model. In this study, mumps viruses bearing variant SH sequences were isolated from contemporary outbreak samples to evaluate the impact of the observed mutations on SH protein function. All isolates with variant SH sequences replicated in interferon-competent cells with no evidence of attenuation. Furthermore, all SH-variant viruses retained the ability to abrogate induction of NF-κB-mediated innate immune signaling in infected cells. Ectopic expression of variant mumps SH genes is consistent with findings from infection experiments, indicating that the observed abrogation of signaling was not mediated by other viral factors that may modulate innate immune signaling. Molecular surveillance is an important public health tool for monitoring the diversity of circulating mumps viruses and can provide insights into determinants of disease. These findings, in turn, will inform studies employing reverse genetics to elucidate the specific mechanisms of MuV pathogenesis and potential impacts of observed sequence variants on infectivity, fitness, and virulence.IMPORTANCE Mumps virus (MuV) outbreaks occur in the United States despite high coverage with measles, mumps, rubella (MMR) vaccine. Routine genotyping of laboratory-confirmed mumps cases has been practiced in the United States since 2006 to enhance mumps surveillance. This study reports the detection of unusual mutations in the small hydrophobic (SH) protein of contemporary laboratory-confirmed mumps cases and is the first to describe the impact of such mutations on SH protein function. These mutations are predicted to profoundly alter the amino acid sequence of the SH protein, which has been shown to antagonize host innate immune responses; however, they were neither associated with defects in virus replication nor attenuated protein function in vitro, consistent with detection in clinical specimens. A better understanding of the forces governing mumps virus sequence diversity and of the functional consequences of mutations in viral proteins is important for maintaining robust capacity for mumps detection and disease control. |
In vitro inhibition of mumps virus replication by Favipiravir (T-705)
Lawson B , Suppiah S , Rota PA , Hickman CJ , Latner DR . Antiviral Res 2020 180 104849 During the last decade multiple mumps outbreaks have occurred in the U.S. despite high two dose MMR coverage with most cases detected among two dose MMR vaccine recipients. Waning immunity, the evolution of wild-type virus strains, and settings with intense exposure have contributed to the resurgence of mumps. Typically, mumps virus infections resolve without serious clinical sequelae; however, serious complications may occur among unvaccinated or severely immunocompromised individuals. Favipiravir (T-705) has been shown to have in vitro anti-viral activity against a broad range of positive and negative strand RNA viruses. Here, we demonstrate that T-705 inhibits the growth of wildtype and vaccine strains of mumps virus in vitro at low micro-molar concentrations (EC50 8-10muM). We did not observe the development of resistance after five subsequent passages at low concentrations of drug. Both viral RNA and protein synthesis were selectively reduced compared to host mRNA and protein synthesis. Antiviral treatment options for mumps virus infection may be valuable, especially for areas with a high disease burden or for cases with severe complications. These results presented here suggest that further studies are warranted. |
Genetic Characterization of Mumps Viruses Associated with the Resurgence of Mumps in the United States: 2015-2017.
McNall RJ , Wharton AK , Anderson R , Clemmons N , Lopareva EN , Gonzalez C , Espinosa A , Probert WS , Hacker JK , Liu G , Garfin J , Strain A , Boxrud D , Bryant PW , George KS , Davis T , Griesser RH , Shult P , Bankamp B , Hickman CJ , Wroblewski K , Rota PA . Virus Res 2020 281 197935 Despite high coverage with measles, mumps, and rubella vaccine in the United States, outbreaks of mumps occur in close contact settings such as schools, colleges, and camps. Starting in late 2015, outbreaks were reported from several universities, and by the end of 2017, greater than 13,800 cases had been reported nation-wide. In 2013, the CDC and the Association of Public Health Laboratories contracted four Vaccine Preventable Diseases Reference Centers (VPD-RCs) to perform real-time reverse transcription PCR (RT-qPCR) to detect mumps RNA in clinical samples and to determine the genotype. Twelve genotypes of mumps virus are currently recognized by the World Health Organization, and the standard protocol for genotyping requires sequencing the entire gene coding for the small hydrophobic (SH) protein. Phylogenetic analysis of the 1862 mumps samples genotyped from 2015 through 2017 showed that the overall diversity of genotypes detected was low. Only 0.8% of the sequences were identified as genotypes C, H, J, or K, and 0.5% were identified as vaccine strains in genotypes A or N, while most sequences (98.7%) were genotype G. The majority of the genotype G sequences could be included into one of two large groups with identical SH sequences. Within genotype G, a small number of phylogenetically significant outlier sequences were associated with epidemiologically distinct chains of transmission. These results demonstrate that molecular and epidemiologic data can be used to track transmission pathways of mumps virus; however, the limited diversity of the SH sequences may be insufficient for resolving transmission in all outbreaks. |
Qualitative Variation Among Commercial Immunoassays to Detect Measles-Specific IgG.
Latner DR , Sowers SB , Anthony K , Colley H , Badeau C , Coates J , Wong P , Fakile Y , Interiano C , Pannell KB , Leung-Pineda V , Patel MM , Rota PA , Limbago BM , Hickman CJ . J Clin Microbiol 2020 58 (6) Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary re-vaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization (PRN), the gold standard method and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there was good agreement across platforms for IgG negative sera and for samples with intermediate to high levels of IgG. False negative test results occurred in approximately 11% of sera, which had low levels of neutralizing antibody. |
Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis
Lim AG , Walker JG , Mafirakureva N , Khalid GG , Qureshi H , Mahmood H , Trickey A , Fraser H , Aslam K , Falq G , Fortas C , Zahid H , Naveed A , Auat R , Saeed Q , Davies CF , Mukandavire C , Glass N , Maman D , Martin NK , Hickman M , May MT , Hamid S , Loarec A , Averhoff F , Vickerman P . Lancet Glob Health 2020 8 (3) e440-e450 BACKGROUND: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. METHODS: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. FINDINGS: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13.8 million (95% UI 13.4-14.1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26.5% (22.5-30.7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged >/=30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46.8% and decrease incidence by 50.8% (95% UI 46.1-55.0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8.1 billion, reducing to $3.9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION: Pakistan will need to invest about 9.0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING: UNITAID. |
Interim effect evaluation of the hepatitis C elimination programme in Georgia: a modelling study
Walker JG , Kuchuloria T , Sergeenko D , Fraser H , Lim AG , Shadaker S , Hagan L , Gamkrelidze A , Kvaratskhelia V , Gvinjilia L , Aladashvili M , Asatiani A , Baliashvili D , Butsashvili M , Chikovani I , Khonelidze I , Kirtadze I , Kuniholm MH , Otiashvili D , Sharvadze L , Stvilia K , Tsertsvadze T , Zakalashvili M , Hickman M , Martin NK , Morgan J , Nasrullah M , Averhoff F , Vickerman P . Lancet Glob Health 2019 8 (2) e244-e253 BACKGROUND: Georgia has a high prevalence of hepatitis C, with 5.4% of adults chronically infected. On April 28, 2015, Georgia launched a national programme to eliminate hepatitis C by 2020 (90% reduction in prevalence) through scaled-up treatment and prevention interventions. We evaluated the interim effect of the programme and feasibility of achieving the elimination goal. METHODS: We developed a transmission model to capture the hepatitis C epidemic in Georgia, calibrated to data from biobehavioural surveys of people who inject drugs (PWID; 1998-2015) and a national survey (2015). We projected the effect of the administration of direct-acting antiviral treatments until Feb 28, 2019, and the effect of continuing current treatment rates until the end of 2020. Effect was estimated in terms of the relative decrease in hepatitis C incidence, prevalence, and mortality relative to 2015 and of the deaths and infections averted compared with a counterfactual of no treatment over the study period. We also estimated treatment rates needed to reach Georgia's elimination target. FINDINGS: From May 1, 2015, to Feb 28, 2019, 54 313 patients were treated, with approximately 1000 patients treated per month since mid 2017. Compared with 2015, our model projects that these treatments have reduced the prevalence of adult chronic hepatitis C by a median 37% (95% credible interval 30-44), the incidence of chronic hepatitis C by 37% (29-44), and chronic hepatitis C mortality by 14% (3-30) and have prevented 3516 (1842-6250) new infections and averted 252 (134-389) deaths related to chronic hepatitis C. Continuing treatment of 1000 patients per month is predicted to reduce prevalence by 51% (42-61) and incidence by 51% (40-62), by the end of 2020. To reach a 90% reduction by 2020, treatment rates must increase to 4144 (2963-5322) patients initiating treatment per month. INTERPRETATION: Georgia's hepatitis C elimination programme has achieved substantial treatment scale-up, which has reduced the burden of chronic hepatitis C. However, the country is unlikely to meet its 2020 elimination target unless treatment scales up considerably. FUNDING: CDC Foundation, National Institute for Health Research, National Institutes of Health. |
Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood
Rasheed MAU , Hickman CJ , McGrew M , Sowers SB , Mercader S , Hopkins A , Grimes V , Yu T , Wrammert J , Mulligan MJ , Bellini WJ , Rota PA , Orenstein WA , Ahmed R , Edupuganti S . Proc Natl Acad Sci U S A 2019 116 (38) 19071-19076 In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine >/=10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity. |
Notes from the field: Mumps in detention facilities that house detained migrants - United States, September 2018-August 2019
Leung J , Elson D , Sanders K , Marin M , Leos G , Cloud B , McNall RJ , Hickman CJ , Marlow M . MMWR Morb Mortal Wkly Rep 2019 68 (34) 749-750 On October 12, 2018, five confirmed cases of mumps among migrants who had been transferred between two detention facilities were reported by the facilities to the Texas Department of State Health Services (TDSHS). By December 11, eight Texas detention facilities and six facilities in five other states had reported 67 mumps cases to U.S. Immigration and Customs Enforcement (ICE) Health Service Corps (IHSC) or local health departments. On December 12, TDSHS contacted CDC to discuss mumps control in detention facilities and facilitate communication with IHSC. During January 4–17, 2019, six more state health departments reported new cases in detention facilities, which prompted CDC and IHSC to launch a coordinated national outbreak response. |
Measles outbreak at a privately operated detention facility: Arizona, 2016
Venkat H , Briggs G , Brady S , Komatsu K , Hill C , Leung J , Patel M , Livar E , Su CP , Kassem A , Sowers SB , Mercader S , Rota PA , Elson D , Timme E , Robinson S , Fitzpatrick K , Franco J , Hickman C , Gastanaduy PA . Clin Infect Dis 2019 68 (12) 2018-2025 BACKGROUND: We describe a measles outbreak and control measures implemented at a privately operated detention facility housing US Immigration and Customs Enforcement detainees in 2016. METHODS: Case-patients reported fever and rash and were either laboratory-confirmed or had an epidemiological link to a laboratory-confirmed case-patient. Immunoglobulin G (IgG) avidity and plaque reduction neutralization tests distinguished between primary acute and reinfection case-patients. Measles-specific IgG was measured to assess detainee immunity levels. We compared attack rates (ARs) among detainees and staff, between IgG-negative and IgG-positive detainees, and by detainee housing units and sexes. RESULTS: We identified 32 measles case-patients (23 detainees, 9 staff); rash onsets were during 6 May-26 June 2016. High IgG avidity and neutralizing-antibody titers >40000 to measles (indicating reinfection) were identified in 18 (95%) and 15 (84%) of 19 tested case-patients, respectively. Among 205 unit A detainees tested for presumptive immunity, 186 (91%) had detectable IgG. Overall, the AR was 1.65%. ARs were significantly higher among detainees in unit A (7.05%) compared with units B-F (0.59%), and among male (2.33%) compared with female detainees (0.38%); however, ARs were not significantly different between detainees and staff or between IgG-negative and IgG-positive detainees. Control measures included the vaccination of 1424 of 1425 detainees and 190 of 510 staff, immunity verification for 445 staff, case-patient isolation, and quarantine of affected units. CONCLUSIONS: Although ARs were low, measles outbreaks can occur in intense-exposure settings, despite a high population immunity, underscoring the importance of high vaccination coverage and containment in limiting measles transmission. |
Scaling-up hepatitis C prevention and treatment interventions for achieving elimination in the United States - a rural and urban comparison
Fraser H , Vellozzi C , Hoerger TJ , Evans JL , Kral AH , Havens J , Young AM , Stone J , Handanagic S , Hariri S , Barbosa C , Hickman M , Leib A , Martin NK , Nerlander L , Raymond HF , Page K , Zibbell J , Ward JW , Vickerman P . Am J Epidemiol 2019 188 (8) 1539-1551 In the U.S. Hepatitis C virus (HCV) transmission is increasing among people who inject drugs (PWID). Many regions have insufficient prevention intervention coverage. Using modelling, we investigate the impact of scaling-up prevention and treatment interventions on HCV transmission among PWID in Perry County, Kentucky (PC), and San Francisco, California (SF), where HCV sero-prevalence among PWID is >50%. A greater proportion of PWID access medication-assisted treatment (MAT) or syringe service programs (SSP) in urban SF (established community) than rural PC (young, expanding community). We model the proportion of HCV-infected PWID needing HCV-treatment annually to reduce HCV-incidence by 90% by 2030, with and without MAT scale-up (50% coverage, both settings) and SSP scale-up (PC only) from 2017. With current MAT&SSP coverage during 2017-2030, HCV-incidence will increase in PC (21.3 to 22.6 per 100 person-years (/100pyrs)) and decrease in SF (12.9 to 11.9/100pyrs). With concurrent MAT&SSP scale-up, 5%/year of HCV-infected PWID need HCV-treatment in PC to achieve incidence targets; 13%/year without MAT&SSP scale-up. In SF, a similar proportion need HCV-treatment (10%/year) irrespective of MAT scale-up. Reaching the same impact by 2025 requires increases in treatment rates of 45-82%. Achievable provision of HCV-treatment, alongside MAT&SSP scale-up (PC) and MAT scale-up (SF), could reduce HCV-incidence. |
Successes and challenges for preventing measles, mumps and rubella by vaccination
Bankamp B , Hickman C , Icenogle JP , Rota PA . Curr Opin Virol 2019 34 110-116 The measles, mumps and rubella (MMR) vaccine has an outstanding safety record and is highly efficacious. High coverage with MMR has led to the elimination of endemic measles, rubella, and congenital rubella syndrome in the US. The biggest challenges to global measles and rubella control and elimination are insufficient vaccination coverage globally and increasing hesitancy. Despite high two dose coverage rates, mumps has made a resurgence in the US and other countries. Mumps outbreaks have occurred primarily in close contact, high-density settings and most cases had received a second dose 10 or more years previously. Waning humoral immunity and antigenic variation of circulating wild-type mumps strains may play a role in the mumps resurgence. |
Notes From The Field: Mumps outbreak in a recently vaccinated population - Kosrae, Federated States of Micronesia, August-December, 2017
McKay SL , Kambui A , Taulung LA , Tippins A , Eckert M , Wharton AK , McNall RJ , Hickman C , Hancock WT , Apaisam C , Judicpa P , Patel M , Routh J . MMWR Morb Mortal Wkly Rep 2019 68 (4) 95-96 On August 6, 2017, the Kosrae Department of Health Services (KDHS) in the Federated States of Micronesia identified a confirmed case of mumps in a Kosrae resident who had 2 documented doses of measles-mumps-rubella (MMR) vaccine. The patient aged 18 years had recently traveled to Seattle, Washington, which was experiencing a mumps outbreak among members of its Pacific Islander population. Other Pacific Islands were concurrently experiencing large mumps outbreaks (1,2), in some places exceeding 500 cases, raising concern about the possibility of a similar outbreak in Kosrae. By October 6, KDHS had identified 17 cases (nine laboratory confirmed and eight suspected [clinically diagnosed as parotitis]) on the island (population 6,600) (Figure), with an attack rate of 14 cases per 1,000 residents in the primary affected municipality. At the request of KDHS, CDC deployed a team on October 17 to assist KDHS in investigation and control activities. The KDHS-CDC team conducted active surveillance to assess outbreak magnitude, interviewed mumps patients, collected specimens for laboratory testing, and reviewed patients’ vaccination records. KDHS conducted islandwide awareness campaigns about the outbreak and mumps prevention measures, and highlighted the importance of vaccination. |
Development and use of an endpoint titration assay to characterize mumps IgG avidity following measles, mumps, and rubella vaccination and wild-type mumps infection
Mercader S , McGrew M , Sowers SB , Williams NJ , Bellini WJ , Hickman CJ . mSphere 2018 3 (5) Waning mumps IgG antibody and incomplete IgG avidity maturation may increase susceptibility to mumps virus infection in some vaccinees. To measure mumps IgG avidity, serum specimens serially diluted to the endpoint were incubated on a commercial mumps-specific IgG enzyme immunoassay and treated with the protein denaturant diethylamine (60 mM, pH 10). End titer avidity indices (etAIs [percent ratio of detected diethylamine-resistant IgG at endpoint]) were calculated. Unpaired serum specimens (n = 108) from 15-month-old children living in a low-incidence setting were collected 1 month and 2 years after the first measles, mumps, and rubella vaccine dose (MMR1) and tested for mumps avidity. Per the receiver operating characteristic curve, the avidity assay is accurate (area under the curve, 0.994; 95% confidence interval [CI], 0.956 to 1.000), 96.5% sensitive (95% CI, 87.9 to 99.6%), and 92.2% specific (95% CI, 81.1 to 97.8%) at an etAI of 30%. When 9 sets of paired serum specimens collected 1 to 60 months post-MMR1 were tested for mumps and measles IgG avidity using comparable methods, the mumps etAI increased from 11% to 40 to 60% in 6 months. From 6 to 60 months, avidity was sustained at a mean etAI of 50% (95% CI, 46 to 54%), significantly lower (P < 0.0001) than the mean measles etAI of 80% (95% CI, 74 to 86%). Mean etAIs in children 2 years post-MMR1 (n = 51), unvaccinated adults with distant mumps disease (n = 29), and confirmed mumps cases (n = 23) were 54, 62, and 57%, respectively. A mumps-specific endpoint avidity assay was developed and validated, and mumps avidity was determined to be generally sustained at etAIs of 40 to 60%, reaching etAIs of >80% in some individuals.IMPORTANCE Numerous outbreaks of mumps have occurred in the United States among two-dose measles-mumps-rubella (MMR)-vaccinated populations since 2006. The avidity of mumps-specific IgG antibodies may affect susceptibility to mumps virus infection in some vaccinated individuals. To accurately measure mumps avidity, we developed and validated a mumps-specific IgG avidity assay that determines avidity at the endpoint titer of serially diluted serum specimens, providing results that are independent of IgG concentration. At low antibody titers, endpoint methods are considered more accurate than methods that determine avidity at a single dilution. We determined that 6 months after the first MMR dose, mumps IgG avidity is high and generally sustained at avidity indices of 40 to 60%, reaching values of >80% in some individuals. Additionally, 4% (4/103) of individuals had avidity indices of </=30% (low avidity) 2 years after vaccination. Inadequate mumps avidity maturation may be one factor influencing susceptibility to mumps virus infection among previously vaccinated or naturally infected individuals. |
Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination
Lim AG , Qureshi H , Mahmood H , Hamid S , Davies CF , Trickey A , Glass N , Saeed Q , Fraser H , Walker JG , Mukandavire C , Hickman M , Martin NK , May MT , Averhoff F , Vickerman P . Int J Epidemiol 2018 47 (2) 550-560 Background: The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide. Methods: We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets. Results: With no further treatment (currently approximately 150 000 treated annually) during 2016-30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually. Conclusions: Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan's HCV burden will increase markedly. |
Measles, mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine
Seagle EE , Bednarczyk RA , Hill T , Fiebelkorn AP , Hickman CJ , Icenogle JP , Belongia EA , McLean HQ . Vaccine 2018 36 (6) 818-826 BACKGROUND: Antibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree of individual variation. Yet, individual variations and differences across antigens are not well understood. To better understand potential implications on individual and population susceptibility, we reanalyzed longitudinal data to identify patterns of seropositivity and persistence. METHODS: Children vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4-6years of age were followed up to 12years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects. RESULTS: Most of the 302 participants were seropositive throughout follow-up (96% measles, 88% mumps, 79% rubella). The rate of antibody decline was associated with MMR2 response and baseline titer for measles and age at first dose of MMR (MMR1) for rubella. No demographic or clinical factors were associated with mumps rate of decline. One month post-MMR2, geometric mean titer (GMT) to measles was high (3892mIU/mL), but declined on average 9.7% per year among those with the same baseline titer and <2-fold increase post-MMR2. Subjects with >/=2-fold experienced a slower decline (</=7.4%). GMT to rubella was 149 one month post-MMR2, declining 2.6% and 5.9% per year among those who received MMR1 at 12-15months and >15months, respectively. GMT to mumps one month post-MMR2 was 151, declining 9.2% per year. Only 14% of subjects had the same persistence trends for all antigens. CONCLUSIONS: The rate of antibody decay varied substantially among individuals and the 3 antigen groups. A fast rate of decline coupled with high variation was observed for mumps, yet no predictors were identified. Future research should focus on better understanding waning titers to mumps and its impacts on community protection and individual susceptibility, in light of recent outbreaks in vaccinated populations. |
Mumps virus nucleoprotein and hemagglutinin-specific antibody response following a third dose of measles mumps rubella vaccine
Latner DR , Parker Fiebelkorn A , McGrew M , Williams NJ , Coleman LA , McLean HQ , Rubin S , Hickman CJ . Open Forum Infect Dis 2017 4 (4) ofx263 Background: Recent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised questions regarding the potential benefits of a third dose of vaccine (MMR3). If MMR3 provides a sustained elevation in mumps antibody, it may be beneficial for certain at-risk groups or as an outbreak control measure. Methods: Sera were collected immediately prior to MMR3 and at 1 month and 1 year post-MMR3 from 656 healthy adults aged 18-28 years in a nonoutbreak setting. Immunoglobulin G (IgG) was measured by enzyme-linked immunosorbent assay (ELISA) using whole mumps virus (commercial ELISA), hemagglutinin (HN; major neutralizing target), and nucleoprotein (NP; immunodominant) antigens. ELISA measurements were compared with in vitro plaque reduction neutralization (PRN) titers, and baseline antibody was compared with post-MMR3 levels. Results: There were modest but statistically significant (P < .05) increases in mumps antibody at 1 month post-MMR3 by all 3 ELISA methods and by PRN titer. At 1 year post-MMR3, mumps antibody declined toward baseline but remained elevated (P < .05). The correlation between PRN titers and ELISA measurements was poor (r(2) = .49), although sera with the highest amount of HN IgG also had the highest PRN titers. Conclusions: Individuals with the lowest baseline PRN titers had the largest increase in frequency of samples that became positive for HN and NP by ELISA. A third dose of MMR may benefit certain individuals with a low level of mumps virus-neutralizing antibody, especially in the context of an outbreak or other high-risk setting. Additionally, poor correlation among serologic tests does not allow effective prediction of PRN titer by ELISA. |
Notes from the field: Absence of asymptomatic mumps virus shedding among vaccinated college students during a mumps outbreak - Washington, February-June 2017
Bonwitt J , Kawakami V , Wharton A , Burke RM , Murthy N , Lee A , Dell B , Kay M , Duchin J , Hickman C , McNall RJ , Rota PA , Patel M , Lindquist S , DeBolt C , Routh J . MMWR Morb Mortal Wkly Rep 2017 66 (47) 1307-1308 On February 8, 2017, a suspected case of mumps in a member of a fraternity or sorority at the University of Washington, Seattle campus (UW) was reported to Public Health—Seattle & King County (PHSKC). Additional confirmed and probable mumps cases were subsequently identified among UW students and staff members according to the national case definition.* By July 19, 2017, a total of 42 (16 confirmed and 26 probable) mumps cases were reported among UW students and associated community members, with symptom onset February 6–June 4 (Figure). |
Importance and contribution of community, social, and healthcare risk factors for hepatitis C infection in Pakistan
Trickey A , May MT , Davies C , Qureshi H , Hamid S , Mahmood H , Saeed Q , Hickman M , Glass N , Averhoff F , Vickerman P . Am J Trop Med Hyg 2017 97 (6) 1920-1928 Pakistan has a high prevalence of hepatitis C virus (HCV) infection, estimated at 4.9% (2,290/46,843) in the 2007 national HCV seroprevalence survey. We used data from this survey to assess the importance of risk factor associations with HCV prevalence in Pakistan. Exposures were grouped as community (going to the barbers, sharing smoking equipment, having an ear/nose piercing, tattoo, or acupuncture), healthcare (ever having hemodialysis, blood transfusion, or ≥ 5 injections in the last year), demographic (marital status and age), and socio-economic (illiterate or laborer). We used mutually adjusted multivariable regression analysis, stratified by sex, to determine associations with HCV infection, their population attributable fraction, and how risk of infection accumulates with multiple exposures. Strength of associations was assessed using adjusted odds ratios (aOR). Community [aOR females 1.5 (95% confidence interval [CI]: 1.2, 1.8); males 1.2 (1.1, 1.4)] and healthcare [females 1.4 (1.2, 1.6); males 1.2 (1.1, 1.4)] exposures, low socio-economic status [females 1.6 (1.3, 1.80); males 1.3 (1.2, 1.5)], and marriage [females 1.5 (1.2, 1.9); males 1.4 (1.1, 1.8)] were associated with increased HCV infection. Among married women, the number of children was associated with an increase in HCV infection; linear trend aOR per child 1.06 (1.01, 1.11). Fewer infections could be attributed to healthcare exposures (females 13%; males 6%) than to community exposures (females 25%; males 9%). Prevalence increased from 3% to 10% when cumulative exposures increased from 1 to ≥ 4 [aOR per additional exposure for females 1.5 (1.4, 1.6); males 1.2 (1.2, 1.3)]. A combination of community, healthcare, and other factors appear to drive the Pakistan HCV epidemic, highlighting the need for a comprehensive array of prevention strategies. |
Mumps outbreak in a highly vaccinated university-affiliated setting before and after a measles-mumps-rubella (MMR) vaccination campaign-Iowa, July 2015-May 2016
Shah M , Quinlisk P , Weigel A , Riley J , James L , Patterson J , Hickman C , Rota PA , Schicker R , Clemmons N , Kalas N , Cardemil C . Clin Infect Dis 2017 66 (1) 81-88 Background: In response to a mumps outbreak at the University of Iowa and surrounding community, university, state, and local health officials implemented a vaccination campaign targeting students <25 years of age with an additional dose of measles-mumps-rubella (MMR) vaccine. Over 4,700 vaccine campaign doses were administered; 97% were documented third doses. We describe the epidemiology of the outbreak before and after the campaign, focusing on cases in university students. Methods: Mumps cases were identified from reportable disease databases and university health system records. Detailed information on student cases was obtained from interviews, medical chart abstractions, university and state vaccination records, and state public health laboratory results. Pre- and post-campaign incidence among students, university faculty/staff, and community members <25 vs. ≥25 years old were compared using Fisher's exact test. Multivariable regression modeling was performed to identify variables associated with a positive mumps polymerase chain reaction test. Results: Of 453 cases in the county, 301 (66%) occurred in university students. Student cases were primarily undergraduates (90%) and highly vaccinated (86% had 2 MMR doses, and 12% had 3 MMR doses). Fewer cases occurred in students after the campaign (75; 25%) than before (226; 75%). Cases in the target group (students <25 years of age) declined 9% post-campaign (p = 0.01). A positive mumps PCR test was associated with the presence of parotitis and early sample collection, and inversely associated with recent receipt of MMR vaccine. Conclusions: Following a large additional dose MMR vaccination campaign, fewer mumps cases occurred overall and in the target population. |
Scaling up HCV prevention and treatment interventions in rural USA - model projections for tackling an increasing epidemic
Fraser H , Zibbell J , Hoerger T , Hariri S , Vellozzi C , Martin NK , Kral AH , Hickman M , Ward JW , Vickerman P . Addiction 2017 113 (1) 173-182 BACKGROUND AND AIMS: Effective strategies are needed to address dramatic increases in hepatitis C virus (HCV) infection among people who inject drugs (PWID) in rural settings of the United States (US). We determined the required scale-up of HCV treatment with or without scale-up of HCV prevention interventions to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025 and 2030 in a rural US setting. DESIGN: An ordinary differential equation model of HCV transmission calibrated to HCV epidemiological data obtained primarily from a HIV-outbreak investigation in Indiana. SETTING: Scott County, Indiana (population 24,181), USA, a rural setting with negligible baseline interventions, increasing HCV epidemic since 2010, and 55.3% chronic HCV prevalence amongst PWID in 2015 PARTICIPANTS: PWID MEASUREMENTS: Required annual HCV treatments per 1000 PWID (and initial annual percentage of infections treated) to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025/30, either with or without scaling-up syringe service programs (SSPs) and medication-assisted treatment (MAT) to 50% coverage. Sensitivity analyses considered whether this impact could be achieved without retreatment of reinfections, and whether greater intervention scale-up was required due to the increasing epidemic in this setting. FINDINGS: To achieve a 90% reduction in incidence and prevalence by 2030, without MAT and SSP scale-up, 159 per 1000 PWID (initially 25% of infected PWID) need to be HCV-treated annually. However, with MAT and SSP scaled-up, treatment rates are halved (89 per 1000 annually or 15%). To reach the same target by 2025 with MAT and SSP scaled-up, 121 per 1000 PWID (20%) need treatment annually. These treatment requirements are 3-fold higher than if the epidemic was stable, and the impact targets are unattainable without retreatment. CONCLUSIONS: Combined scale-up of hepatitis C virus (HCV) treatment and prevention interventions is needed to decrease the increasing burden of HCV incidence and prevalence in rural Indiana, USA, by 90% by 2025/30. |
A measles outbreak in an underimmunized Amish community in Ohio
Gastanaduy PA , Budd J , Fisher N , Redd SB , Fletcher J , Miller J , McFadden DJ 3rd , Rota J , Rota PA , Hickman C , Fowler B , Tatham L , Wallace GS , de Fijter S , Parker Fiebelkorn A , DiOrio M . N Engl J Med 2016 375 (14) 1343-1354 Background Although measles was eliminated in the United States in 2000, importations of the virus continue to cause outbreaks. We describe the epidemiologic features of an outbreak of measles that originated from two unvaccinated Amish men in whom measles was incubating at the time of their return to the United States from the Philippines and explore the effect of public health responses on limiting the spread of measles. Methods We performed descriptive analyses of data on demographic characteristics, clinical and laboratory evaluations, and vaccination coverage. Results From March 24, 2014, through July 23, 2014, a total of 383 outbreak-related cases of measles were reported in nine counties in Ohio. The median age of case patients was 15 years (range, <1 to 53); a total of 178 of the case patients (46%) were female, and 340 (89%) were unvaccinated. Transmission took place primarily within households (68% of cases). The virus strain was genotype D9, which was circulating in the Philippines at the time of the reporting period. Measles-mumps-rubella (MMR) vaccination coverage with at least a single dose was estimated to be 14% in affected Amish households and more than 88% in the general (non-Amish) Ohio community. Containment efforts included isolation of case patients, quarantine of susceptible persons, and administration of the MMR vaccine to more than 10,000 persons. The spread of measles was limited almost exclusively to the Amish community (accounting for 99% of case patients) and affected only approximately 1% of the estimated 32,630 Amish persons in the settlement. Conclusions The key epidemiologic features of a measles outbreak in the Amish community in Ohio were transmission primarily within households, the small proportion of Amish people affected, and the large number of people in the Amish community who sought vaccination. As a result of targeted containment efforts, and high baseline coverage in the general community, there was limited spread beyond the Amish community. (Funded by the Ohio Department of Health and the Centers for Disease Control and Prevention.). |
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