Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-12 (of 12 Records) |
Query Trace: Macklin N[original query] |
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Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine
Senkpeil L , Bhardwaj J , Little MR , Holla P , Upadhye A , Fusco EM , Swanson Ii PA , Wiegand RE , Macklin MD , Bi K , Flynn BJ , Yamamoto A , Gaskin EL , Sather DN , Oblak AL , Simpson E , Gao H , Haining WN , Yates KB , Liu X , Murshedkar T , Richie TL , Sim BKL , Otieno K , Kariuki S , Xuei X , Liu Y , Polidoro RB , Hoffman SL , Oneko M , Steinhardt LC , Schmidt NW , Seder RA , Tran TM . JCI Insight 2024 A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole sporozoite PfSPZ Vaccine in African infants. Innate immune activation and myeloid signatures at pre-vaccination baseline correlated with protection from Pf parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ Vaccine dose. Machine learning identified spliceosome, proteosome, and resting dendritic cell signatures as pre-vaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline CSP-specific IgG predicted non-protection. Pre-vaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T-cell responses post-vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naïve mice while diminishing the CD8+ T-cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity of whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggest that PfSPZ Vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways. |
Mucosal immunity to poliovirus in children 0-15 years of age: A community-based study in Karachi, Pakistan in 2019
Saleem AF , Kazi ZU , Zehra SM , Parkar S , Macklin G , Sifontes G , Mainou BA , Alam M , Lopez Cavestany R , Mach O . J Infect Dis 2024 This study assesses poliovirus type 1 (PV1) immunity in children to inform the contribution of mucosal immunity in and preventing poliovirus circulation. A community-based study was conducted in peri-urban Karachi, Pakistan. Randomly selected children (0-15 years) received oral poliovirus vaccine (OPV) challenge dose. Blood and stool samples were collected at several time points and evaluated for polio-neutralizing antibodies and serotype-specific poliovirus, respectively. 81/589 (14%) children excreted PV1 7 days post-OPV-challenge; 70/81 (86%) were seropositive at baseline. 12/610 (2%) were asymptomatic Wild Poliovirus Type 1 (WPV1) excretors. Most poliovirus excretors had humoral immunity, suggesting mucosal immunity in these children likely waned or never developed. Without mucosal immunity, they are susceptible to poliovirus infection, shedding, and transmission. Asymptomatic WPV1 excretion suggests undetected poliovirus circulation within the community. |
Early serial echocardiographic and ultrasonographic findings in critically ill patients with COVID-19
Lanspa MJ , Dugar SP , Prigmore HL , Boyd JS , Rupp JD , Lindsell CJ , Rice TW , Qadir N , Lim GW , Shiloh AL , Dieiev V , Gong MN , Fox SW , Hirshberg EL , Khan A , Kornfield J , Schoeneck JH , Macklin N , Files DC , Gibbs KW , Prekker ME , Parsons-Moss D , Bown M , Olsen TD , Knox DB , Cirulis MM , Mehkri O , Duggal A , Tenforde MW , Patel MM , Self WH , Brown SM . CHEST Crit Care 2023 1 (1) 100002 BACKGROUND: Cardiac function of critically ill patients with COVID-19 generally has been reported from clinically obtained data. Echocardiographic deformation imaging can identify ventricular dysfunction missed by traditional echocardiographic assessment. RESEARCH QUESTION: What is the prevalence of ventricular dysfunction and what are its implications for the natural history of critical COVID-19? STUDY DESIGN AND METHODS: This is a multicenter prospective cohort of critically ill patients with COVID-19. We performed serial echocardiography and lower extremity vascular ultrasound on hospitalization days 1, 3, and 8. We defined left ventricular (LV) dysfunction as the absolute value of longitudinal strain of < 17% or left ventricle ejection fraction (LVEF) of < 50%. Primary clinical outcome was inpatient survival. RESULTS: We enrolled 110 patients. Thirty-nine (35.5%) died before hospital discharge. LV dysfunction was present at admission in 38 patients (34.5%) and in 21 patients (36.2%) on day 8 (P = .59). Median baseline LVEF was 62% (interquartile range [IQR], 52%-69%), whereas median absolute value of baseline LV strain was 16% (IQR, 14%-19%). Survivors and nonsurvivors did not differ statistically significantly with respect to day 1 LV strain (17.9% vs 14.4%; P = .12) or day 1 LVEF (60.5% vs 65%; P = .06). Nonsurvivors showed worse day 1 right ventricle (RV) strain than survivors (16.3% vs 21.2%; P = .04). INTERPRETATION: Among patients with critical COVID-19, LV and RV dysfunction is common, frequently identified only through deformation imaging, and early (day 1) RV dysfunction may be associated with clinical outcome. |
Two-year duration of immunity of inactivated poliovirus vaccine: A follow-up study in Pakistan in 2020
Saleem AF , Parkar S , Zehra SM , Kazi Z , Pethani A , Zhang Y , Mainou BA , Cavestany RL , Macklin G , Jeyaseelan V , Mach O . J Infect Dis 2023 This was a follow-up study conducted in 2020 assessing changes in levels of type 2 poliovirus-neutralizing antibodies two years post-immunization in children who received inactivated poliovirus vaccine (IPV) in Karachi, Pakistan. Unexpectedly, the findings revealed an increase in seroprevalence of type 2 antibodies from 73.1% to 81.6% one and two years after IPV, respectively. The increase in type 2 immunity could result from the intensive transmission of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Karachi during the second year of IPV administration. This study suggests that the cVDPV2 outbreak detected in Pakistan infected large proportions of children in Karachi. Clinical Trial Registration NCT03286803. |
Poliovirus antibodies following two rounds of campaigns with a type 2 novel oral poliovirus vaccine in Liberia: a clustered, population-based seroprevalence survey
Kennedy SB , Macklin GR , Mason Ross G , Lopez Cavestany R , Moukom RA , Jones KAV , Mainou BA , Massaquoi MBF , Kieh MWS , Mach O . Lancet Glob Health 2023 11 (6) e917-e923 BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was administered in Liberia in response to an outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in 2021. We conducted a serological survey of polio antibodies after two national campaigns with nOPV2. METHODS: This clustered, cross-sectional, population-based seroprevalence survey was conducted in children aged 0-59 months, more than 4 weeks after the second nOPV2 vaccination round. We used a clustered sampling method in four geographical regions of Liberia, followed by a simple random sampling of households. One eligible child was randomly selected per household. Dried blood spot specimens were taken and vaccination history was recorded. The antibody titres against all three poliovirus serotypes were assessed using standard microneutralisation assays done at the US Centers for Disease Control and Prevention in Atlanta, GA, USA. FINDINGS: Analysable data were obtained from 436 (87%) of 500 enrolled participants. Of these, 371 (85%) children were reported via parental recall to have received two nOPV2 doses, 43 (10%) received one dose, and 22 (5%) received no doses. The seroprevalence against type 2 poliovirus was 38·3% (95% CI 33·7-43·0; 167 of 436 participants). No significant difference was observed between type 2 seroprevalence in children aged 6 months or older who were reported to have received two doses of nOPV2 (42·1%, 95% CI 36·8-47·5; 144 of 342), one dose (28·0%, 12·1-49·4; seven of 25), or no doses (37·5%, 8·5-75·5; three of eight; p=0·39). The seroprevalence against type 1 was 59·6% (54·9-64·3; 260 of 436), and the seroprevalence against type 3 was 53·0% (48·2-57·7; 231 of 436). INTERPRETATION: Unexpectedly, the data showed low type 2 seroprevalence after two reported doses of nOPV2. This finding is probably affected by the lower oral poliovirus vaccine immunogenicity previously demonstrated in resource-limited settings, with high prevalence of chronic intestinal infections in children and other factors discussed herein. Our results provide the first assessment of nOPV2 performance in outbreak response in the African region. FUNDING: WHO and Rotary International. |
Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021
Mirzoev A , Macklin GR , Zhang Y , Mainou BA , Sadykova U , Olsavszky VS , Huseynov S , Ruziev M , Saidzoda F , Bobokhonova M , Mach O . Lancet Glob Health 2022 10 (12) e1807-e1814 BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was used to control an outbreak of type 2 circulating vaccine derived poliovirus (cVDPV2) in Tajikistan, in 2021. We measured seroconversion and seroprevalence of type 2 polio antibodies in children who were reported to have received two doses of nOPV2 in outbreak response campaigns. METHODS: In this community serosurvey, children born after Jan 1, 2016 were enrolled from seven districts in Tajikistan. Dried blood spot cards were collected before nOPV2 campaigns and after the first and second rounds of the campaigns and were sent to the Centers for Disease Control and Prevention (Atlanta, GA, USA) for microneutralisation assay to determine presence of polio antibodies. The primary endpoint was to assess change in seroprevalence and seroconversion against poliovirus serotype 2 after one and two doses of nOPV2. FINDINGS: 228 (97%) of 236 enrolled children were included in the analysis. The type 2 antibody seroprevalence was 26% (53/204; 95% CI 20 to 33) before nOPV2, 77% (161/210; 70 to 82) after one dose of nOPV2, and 83% (174/209; 77 to 88) after two doses of nOPV2. The increase in seroprevalence was statistically significant between baseline and after one nOPV2 dose (51 percentage points [42 to 59], p<00001), but not between the first and second doses (6 percentage points [-2 to 15], p=012). Seroconversion from the first nOPV2 dose, 67% (89/132; 59 to 75), was significantly greater than that from the second nOPV2 dose, 44% (20/45; 30 to 60; (2) p=0010). Total seroconversion after two nOPV2 doses was 77% (101/132; 68 to 83). INTERPRETATION: Our study demonstrated strong immune responses following nOPV2 outbreak response campaigns in Tajikistan. Our results support previous clinical trial data on the generation of poliovirus type 2 immunity by nOPV2 and provide evidence that nOPV2 can be appropriate for the cVDPV2 outbreak response. The licensure and WHO prequalification of nOPV2 should be accelerated to facilitate wider use of the vaccine. FUNDING: World Health Organization, Centers for Disease Control and Prevention, and Rotary International. |
Genetic characterization of novel oral polio vaccine type 2 viruses during initial use phase under emergency use listing - worldwide, March-October 2021
Martin J , Burns CC , Jorba J , Shulman LM , Macadam A , Klapsa D , Majumdar M , Bullows J , Frolov A , Mate R , Bujaki E , Castro CJ , Bullard K , Konz J , Hawes K , Gauld J , Blake IM , Mercer LD , Kurji F , Voorman A , Diop OM , Oberste MS , Modlin J , Macklin G , Eisenhawer M , Bandyopadhyay AS , Zipursky S . MMWR Morb Mortal Wkly Rep 2022 71 (24) 786-790 The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) across multiple countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating all forms of polioviruses. Approximately 90% of all cVDPV outbreaks are caused by the type 2 strain of the Sabin vaccine, an oral live, attenuated vaccine; cVDPV outbreaks typically occur in areas of persistently low immunization coverage (1). A novel type 2 oral poliovirus vaccine (nOPV2), produced by genetic modification of the type 2 Sabin vaccine virus genome (2), was developed and evaluated through phase I and phase II clinical trials during 2017-2019. nOPV2 was demonstrated to be safe and well-tolerated, have noninferior immunogenicity, and have superior genetic stability compared with Sabin monovalent type 2 (as measured by preservation of the primary attenuation site [domain V in the 5' noncoding region] and significantly lower neurovirulence of fecally shed vaccine virus in transgenic mice) (3-5). These findings indicate that nOPV2 could be an important tool in reducing the risk for generating vaccine-derived polioviruses (VDPVs) and the risk for vaccine-associated paralytic poliomyelitis cases. Based on the favorable preclinical and clinical data, and the public health emergency of international concern generated by ongoing endemic wild poliovirus transmission and cVDPV type 2 outbreaks, the World Health Organization authorized nOPV2 for use under the Emergency Use Listing (EUL) pathway in November 2020, allowing for its first use for outbreak response in March 2021 (6). As required by the EUL process, among other EUL obligations, an extensive plan was developed and deployed for obtaining and monitoring nOPV2 isolates detected during acute flaccid paralysis (AFP) surveillance, environmental surveillance, adverse events after immunization surveillance, and targeted surveillance for adverse events of special interest (i.e., prespecified events that have the potential to be causally associated with the vaccine product), during outbreak response, as well as through planned field studies. Under this monitoring framework, data generated from whole-genome sequencing of nOPV2 isolates, alongside other virologic data for isolates from AFP and environmental surveillance systems, are reviewed by the genetic characterization subgroup of an nOPV working group of the Global Polio Eradication Initiative. Global nOPV2 genomic surveillance during March-October 2021 confirmed genetic stability of the primary attenuating site. Sequence data generated through this unprecedented global effort confirm the genetic stability of nOPV2 relative to Sabin 2 and suggest that nOPV2 will be an important tool in the eradication of poliomyelitis. nOPV2 surveillance should continue for the duration of the EUL. |
Update on immunodeficiency-associated vaccine-derived polioviruses - worldwide, July 2018-December 2019
Macklin G , Diop OM , Humayun A , Shahmahmoodi S , El-Sayed ZA , Triki H , Rey G , Avagyan T , Grabovac V , Jorba J , Farag N , Mach O . MMWR Morb Mortal Wkly Rep 2020 69 (28) 913-917 Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses. |
Evolving epidemiology of poliovirus serotype 2 following withdrawal of the type 2 oral poliovirus vaccine
Macklin GR , O'Reilly KM , Grassly NC , Edmunds WJ , Mach O , Santhana Gopala Krishnan R , Voorman A , Vertefeuille JF , Abdelwahab J , Gumede N , Goel A , Sosler S , Sever J , Bandyopadhyay AS , Pallansch MA , Nandy R , Mkanda P , Diop OM , Sutter RW . Science 2020 368 (6489) 401-405 While there have been no cases of type-2 wild poliovirus for over 20 years, transmission of type-2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several continents represent a threat to eradication. The withdrawal of the type-2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all poliovirus type 2. Globally, children born after this date have limited immunity to prevent transmission. Using a statistical model, we estimate the emergence date and source of VDPV2s detected between May 2016 and November 2019. Outbreak response campaigns with monovalent OPV2 are the only available method to induce immunity to prevent transmission. Yet, our analysis shows that using monovalent OPV2 is generating more paralytic VDPV2 outbreaks with the potential for establishing endemic transmission. The novel OPV2 is urgently required, alongside a contingency strategy if this vaccine does not materialize or perform as anticipated. |
Prolonged excretion of poliovirus among individuals with primary immunodeficiency disorder: An analysis of the World Health Organization Registry
Macklin G , Liao Y , Takane M , Dooling K , Gilmour S , Mach O , Kew OM , Sutter RW . Front Immunol 2017 8 1103 Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed. |
Low forced expiratory volume is associated with earlier death in sickle cell anemia
Kassim AA , Payne AB , Rodeghier M , Macklin EA , Strunk RC , DeBaun MR . Blood 2015 126 (13) 1544-50 Pulmonary complications result in mortality in adults with sickle cell anemia (SCA). We tested the hypothesis that abnormal pulmonary function was associated with earlier death. A prospective cohort of adults with SCA, followed in the Cooperative Study for Sickle Cell Disease, was constructed using the first pulmonary function test (PFT) at >21 years of age. Spirometry measures: FEV1, FVC, and TLC were categorized based on age, gender, height, and race. Pulmonary function patterns were categorized based on the American Thoracic Society guidelines using both spirometry and lung volumes. A cohort of 430 adults with SCA, mean age 32.6 +/-9.5 years at time of first PFT and a median follow-up of 5.5 years, was evaluated. A total of 63 deaths occurred in the cohort; 47% had normal, 29% restrictive, 8% obstructive, 2% mixed, and 14% non-specific lung function patterns. In the final multi-variable model, lower FEV1% predicted was associated with increased hazard of death [HR per %-predicted 1.02 (95% CI 1.00 - 1.04; p=0.037)], as was older age [HR 1.07 (95% CI 1.04-1.10; p<0.001)], male sex [HR 2.09 (95% CI 1.20-3.65; p=0.010)], higher lactate dehydrogenase levels [HR per mg/dl 1.002 (95% CI 1.00-1.003; p=0.015)], and higher acute chest syndrome incidence rate [HR per event/yr 10.4 (95% CI 3.11-34.8; p<0.001)]. Presence of obstructive (HR 1.18 [95% CI: 0.44-3.20; p=0.740]) and restrictive (HR 1.31 [95% CI: 0.64-2.32; p=0.557]) pulmonary function patterns were not associated with earlier death. Understanding the pathophysiology of a low FEV1% predicted in individuals with SCA is warranted, enabling early intervention for those at risk. |
Reasons for low influenza vaccination coverage among adults in Puerto Rico, influenza season 2013-2014
Arriola CS , Mercado-Crespo MC , Rivera B , Serrano-Rodriguez R , Macklin N , Rivera A , Graitcer S , Lacen M , Bridges CB , Kennedy ED . Vaccine 2015 33 (32) 3829-35 BACKGROUND: Influenza vaccination is recommended annually for all persons 6 months and older. Reports of increased influenza-related morbidity and mortality during the 2013-2014 influenza season raised concerns about low adult influenza immunization rates in Puerto Rico. In order to inform public health actions to increase vaccination rates, we surveyed adults in Puerto Rico regarding influenza vaccination-related attitudes and barriers. METHODS: A random-digit-dialing telephone survey (50% landline: 50% cellphone) regarding influenza vaccination, attitudes, practices and barriers was conducted November 19-25, 2013 among adults in Puerto Rico. Survey results were weighted to reflect sampling design and adjustments for non-response. RESULTS: Among 439 surveyed, 229 completed the survey with a 52% response rate. Respondents' median age was 55 years; 18% reported receiving 2013-2014 influenza vaccination. Among 180 unvaccinated respondents, 38% reported barriers associated with limited access to vaccination, 24% reported they did not want or need influenza vaccination, and 20% reported safety concerns. Vaccinated respondents were more likely to know if they were recommended for influenza vaccination, to report greater perceived risk of influenza illness, and to report being less concerned about influenza vaccine safety (p-value<0.05). Of the 175 respondents who saw a healthcare provider (HCP) since July 1, 2013, 38% reported their HCP recommended influenza vaccination and 17% were offered vaccination. Vaccination rates were higher among adults who received a recommendation and/or offer of influenza vaccination (43% vs. 14%; p-value<0.01). CONCLUSIONS: Failure of HCP to recommend and/or offer influenza vaccination and patient attitudes (low perceived risk of influenza virus infection) may have contributed to low vaccination rates during the 2013-2014 season. HCP and public health practitioners should strongly recommend influenza vaccination and provide vaccinations during clinical encounters or refer patients for vaccination. |
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