Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 37 Records) |
Query Trace: Adler M[original query] |
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SARS-CoV-2 infection, inflammation and birth outcomes in a prospective NYC pregnancy cohort
Gigase FAJ , Jessel RH , Kaplowitz E , Boychuk N , Ohrn S , Ibroci Est , Castro J , Lynch J , Tubassum R , Balbierz A , Molenaar NM , Graziani M , Missall R , Flores T , Stern T , Carreno JM , Krammer F , Adler A , Brody RI , Lesseur C , Chen J , Ellington S , Galang RR , Snead MC , Howell E , Stone J , Bergink V , Dolan S , Lieb W , Rommel AS , de Witte LD , Janevic T . J Reprod Immunol 2024 163 104243 Associations between antenatal SARS-CoV-2 infection and pregnancy outcomes have been conflicting and the role of the immune system is currently unclear. This prospective cohort study investigated the interaction of antenatal SARS-CoV-2 infection, changes in cytokine and HS-CRP levels, birthweight and gestational age at birth. 2352 pregnant participants from New York City (2020-2022) were included. Plasma levels of interleukin (IL)-1β, IL-6, IL-17A and high-sensitivity C-reactive protein (HS-CRP) were quantified in blood specimens obtained across pregnancy. Quantile and linear regression models were conducted to 1) assess the impact of antenatal SARS-CoV-2 infection, overall and by timing of detection of SARS-CoV-2 positivity (< 20 weeks versus ≥ 20 weeks), on birthweight and gestational age at delivery; 2) examine the relationship between SARS-CoV-2 infection and maternal immune changes during pregnancy. All models were adjusted for maternal demographic and obstetric factors and pandemic timing. Birthweight models were additionally adjusted for gestational age at delivery and fetal sex. Immune marker models were also adjusted for gestational age at specimen collection and multiplex assay batch. 371 (15.8%) participants were infected with SARS-CoV-2 during pregnancy, of which 98 (26.4%) were infected at < 20 weeks gestation. Neither SARS-CoV-2 infection in general nor in early or late pregnancy was associated with lower birthweight nor earlier gestational age at delivery. Further, we did not observe cytokine or HS-CRP changes in response to SARS-CoV-2 infection and thus found no evidence to support a potential association between immune dysregulation and the diversity in pregnancy outcomes following infection. |
The Seattle Flu Study: a multi-arm community-based prospective study protocol for assessing influenza prevalence, transmission, and genomic epidemiology (preprint)
Chu HY , Boeckh M , Englund JA , Famulare M , Lutz B , Nickerson DA , Rieder M , Starita LM , Shendure J , Bedford T , Adler A , Brandstetter E , Frazer CD , Han PD , Gulati RK , Hadfield J , Jackson M , Kiavand A , Kimball LE , Lacombe K , Logue JK , Lyon VR , Newman KL , Sibley TR , Zigman Suchsland M , Wolf C . medRxiv 2020 2020.03.02.20029595 Introduction Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterize, and potentially contain new and emerging influenza strains at a population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population.Methods and Analysis Starting in the 2018-19 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses, and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modeling platforms are in development to characterize the regional spread of influenza and other respiratory pathogens.Ethics and Dissemination The study was approved by the University of Washington’s Institutional Review Board. Results will be disseminated through talks at conferences, peer-reviewed publications, and on the study website (www.seattleflu.org).Strengths and limitations of this study- Large-scale multiple-arm study of respiratory illness characterization with collection of samples from individuals in the community as well as in ambulatory care and hospital settings- Integration of sociodemographic, clinical, and geospatial data on a regional level- Multiplex molecular testing for multiple viral and bacterial pathogens and whole genome sequencing of influenza for detailed molecular epidemiologic characterization and transmission mapping- Geographically and socioeconomically diverse sampling of community-based acute respiratory illnessesCompeting Interest StatementAmanda Adler, Elisabeth Brandstetter, Michael Famulare, Chris D. Frazar, Peter D. Han, Reena K. Gulati, James Hadfield, Michael L. Jackson, Anahita Kiavand, Louise E. Kimball, Kirsten Lacombe, Jennifer Logue, Victoria Lyon, Kira L. Newman, Thomas R. Sibley, Jay Shendure, Lea Starita, Monica L. Zigman Suchsland, and Caitlin Wolf declare no competing interests. Helen Y Chu receives research support from Sanofi, Cepheid, and Genentech/Roche and is a consultant for Merck. Janet Englund receives research support to her institution from Astrazeneca, GlaxoSmithKline, Merck, and Novavax and is a consultant for Sanofi Pasteur and Meissa Vaccines.Funding StatementThe Seattle Flu Study is funded through the Brotman Baty Institute. The funder was not involved in the design of the study, does not have any ownership over the management and conduct of the study, the data, or the rights to publishAuthor DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable YesThe data will be accessed only by authorized individuals on the study team. Access to deidentified, aggregated data and analysis code will be publicly available on the study web page (www.seattleflu.org). http://www.seattleflu.org |
Characterizing spatiotemporal variation in transmission heterogeneity during the 2022 mpox outbreak in the USA (preprint)
Love J , LaPrete CR , Sheets TR , Vega Yon GG , Thomas A , Samore MH , Keegan LT , Adler FR , Slayton RB , Spicknall IH , Toth DJA . medRxiv 2023 14 Transmission heterogeneity plays a critical role in the dynamics of an epidemic. During an outbreak of an emerging infectious disease, efforts to characterize transmission heterogeneity are generally limited to quantifications during a small outbreak or a limited number of generations of a larger outbreak. Understanding how transmission heterogeneity itself varies over the course of a large enduring outbreak not only improves understanding of observed disease dynamics but also informs public health strategy and response. In this study, we employ a method, adaptable to other emerging infectious disease outbreaks, to quantify spatiotemporal variation in transmission heterogeneity for the 2022 mpox outbreak in the United States. Based on past research on mpox and following reports of potential superspreading events early in this outbreak, we expected to find high transmission heterogeneity as quantified by the dispersion parameter of the offspring distribution, k. Our methods use maximum likelihood estimation to fit a negative binomial distribution to transmission chain offspring distributions informed by a large mpox contact tracing dataset. We find that, while estimates of transmission heterogeneity varied across the outbreak with spatiotemporal pockets of higher heterogeneity, overall transmission heterogeneity was low. When testing our methods on simulated data from an outbreak with high transmission heterogeneity, k estimate accuracy depended on the contact tracing data completeness. Because the actual contact tracing data had high incompleteness, our values of k estimated from the empirical data may be artificially high. However, it is also possible that our estimates accurately reflect low transmission heterogeneity for the United States mpox outbreak. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Cryptic transmission of SARS-CoV-2 in Washington State.
Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Huang ML , Nalla A , Pepper G , Reinhardt A , Xie H , Shrestha L , Nguyen TN , Adler A , Brandstetter E , Cho S , Giroux D , Han PD , Fay K , Frazar CD , Ilcisin M , Lacombe K , Lee J , Kiavand A , Richardson M , Sibley TR , Truong M , Wolf CR , Nickerson DA , Rieder MJ , Englund JA , Hadfield J , Hodcroft EB , Huddleston J , Moncla LH , Müller NF , Neher RA , Deng X , Gu W , Federman S , Chiu C , Duchin J , Gautom R , Melly G , Hiatt B , Dykema P , Lindquist S , Queen K , Tao Y , Uehara A , Tong S , MacCannell D , Armstrong GL , Baird GS , Chu HY , Shendure J , Jerome KR . medRxiv 2020 Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding. |
Comparison of COVID-19 pandemic waves in 10 countries in Southern Africa, 2020-2021
Smith-Sreen J , Miller B , Kabaghe AN , Kim E , Wadonda-Kabondo N , Frawley A , Labuda S , Manuel E , Frietas H , Mwale AC , Segolodi T , Harvey P , Seitio-Kgokgwe O , Vergara AE , Gudo ES , Dziuban EJ , Shoopala N , Hines JZ , Agolory S , Kapina M , Sinyange N , Melchior M , Mirkovic K , Mahomva A , Modhi S , Salyer S , Azman AS , McLean C , Riek LP , Asiimwe F , Adler M , Mazibuko S , Okello V , Auld AF . Emerg Infect Dis 2022 28 (13) S93-s104 We used publicly available data to describe epidemiology, genomic surveillance, and public health and social measures from the first 3 COVID-19 pandemic waves in southern Africa during April 6, 2020-September 19, 2021. South Africa detected regional waves on average 7.2 weeks before other countries. Average testing volume 244 tests/million/day) increased across waves and was highest in upper-middle-income countries. Across the 3 waves, average reported regional incidence increased (17.4, 51.9, 123.3 cases/1 million population/day), as did positivity of diagnostic tests (8.8%, 12.2%, 14.5%); mortality (0.3, 1.5, 2.7 deaths/1 million populaiton/day); and case-fatality ratios (1.9%, 2.1%, 2.5%). Beta variant (B.1.351) drove the second wave and Delta (B.1.617.2) the third. Stringent implementation of safety measures declined across waves. As of September 19, 2021, completed vaccination coverage remained low (8.1% of total population). Our findings highlight opportunities for strengthening surveillance, health systems, and access to realistically available therapeutics, and scaling up risk-based vaccination. |
Impact of an intensive facility-community case management intervention on 6-month HIV outcomes among select key and priority populations in Uganda
Meya DB , Kiragga AN , Nalintya E , Banturaki G , Akullo J , Kalyesubula P , Sessazi P , Bitakalamire H , Kabanda J , Kalamya JN , Namale A , Bateganya M , Kagaayi J , Gutreuter S , Adler MR , Mitruka K . AIDS Res Ther 2022 19 (1) 62 INTRODUCTION: Key and priority populations (with risk behaviours and health inequities) are disproportionately affected by HIV in Uganda. We evaluated the impact of an intensive case management intervention on HIV treatment outcomes in Kalangala District, predominantly inhabited by fisher folk and female sex workers. METHODS: This quasi-experimental pre-post intervention evaluation included antiretroviral therapy naïve adults aged ≥ 18 years from six health facilities in the pre-intervention (Jan 1, 2017-December 31, 2017) and intervention phase (June 13, 2018-June 30, 2019). The primary outcomes were 6-month retention and viral suppression (VS) before and after implementation of the intervention involving facility and community case managers who supported participants through at least the first three months of ART. We used descriptive statistics to compared the characteristics, overall outcomes (i.e., retention, lost to follow up, died), and VS of participants by phase, and used mixed-effects logistic regression models to determine factors associated with 6-month retention in care. Marginal (averaging over facilities) probabilities of retention were computed from the final multivariable model. RESULTS: We enrolled 606 and 405 participants in the pre-intervention and intervention phases respectively. Approximately 75% of participants were aged 25-44 years, with similar age and gender distributions among phases. Approximately 46% of participants in the intervention were fisher folk and 9% were female sex workers. The adjusted probability of 6-month retention was higher in the intervention phase, 0.83 (95% CI: 0.77-0.90) versus pre-intervention phase, 0.73 (95% CI: 0.69-0.77, p = 0.03). The retention probability increased from 0.59 (0.49-0.68) to 0.73 (0.59-0.86), p = 0.03 among participants aged 18-24 years, and from 0.75 (0.71-0.78) to 0.85 (0.78-0.91), p = 0.03 among participants aged ≥ 25 years. VS (< 1,000 copies/mL) was approximately 87% in both phases. CONCLUSIONS: After implementation of the case management intervention, we observed significant improvement in 6-month retention in all age groups of a highly mobile population of predominantly fisher folk. |
Epidemiologic and clinical features of children and adolescents aged <18 years with monkeypox - United States, May 17-September 24, 2022
Hennessee I , Shelus V , McArdle CE , Wolf M , Schatzman S , Carpenter A , Minhaj FS , Petras JK , Cash-Goldwasser S , Maloney M , Sosa L , Jones SA , Mangla AT , Harold RE , Beverley J , Saunders KE , Adams JN , Stanek DR , Feldpausch A , Pavlick J , Cahill M , O'Dell V , Kim M , Alarcón J , Finn LE , Goss M , Duwell M , Crum DA , Williams TW , Hansen K , Heddy M , Mallory K , McDermott D , Cuadera MKQ , Adler E , Lee EH , Shinall A , Thomas C , Ricketts EK , Koonce T , Rynk DB , Cogswell K , McLafferty M , Perella D , Stockdale C , Dell B , Roskosky M , White SL , Davis KR , Milleron RS , Mackey S , Barringer LA , Bruce H , Barrett D , D'Angeli M , Kocharian A , Klos R , Dawson P , Ellington SR , Mayer O , Godfred-Cato S , Labuda SM , McCormick DW , McCollum AM , Rao AK , Salzer JS , Kimball A , Gold JAW . MMWR Morb Mortal Wkly Rep 2022 71 (44) 1407-1411 Data on monkeypox in children and adolescents aged <18 years are limited (1,2). During May 17-September 24, 2022, a total of 25,038 monkeypox cases were reported in the United States,(dagger) primarily among adult gay, bisexual, and other men who have sex with men (3). During this period, CDC and U.S. jurisdictional health departments identified Monkeypox virus (MPXV) infections in 83 persons aged <18 years, accounting for 0.3% of reported cases. Among 28 children aged 0-12 years with monkeypox, 64% were boys, and most had direct skin-to-skin contact with an adult with monkeypox who was caring for the child in a household setting. Among 55 adolescents aged 13-17 years, most were male (89%), and male-to-male sexual contact was the most common presumed exposure route (66%). Most children and adolescents with monkeypox were non-Hispanic Black or African American (Black) (47%) or Hispanic or Latino (Hispanic) (35%). Most (89%) were not hospitalized, none received intensive care unit (ICU)-level care, and none died. Monkeypox in children and adolescents remains rare in the United States. Ensuring equitable access to monkeypox vaccination, testing, and treatment is a critical public health priority. Vaccination for adolescents with risk factors and provision of prevention information for persons with monkeypox caring for children might prevent additional infections. |
The influence of structural racism, pandemic stress, and SARS-CoV-2 infection during pregnancy with adverse birth outcomes.
Janevic T , Lieb W , Ibroci E , Lynch J , Lieber M , Molenaar NM , Rommel AS , de Witte L , Ohrn S , Carreño JM , Krammer F , Zapata LB , Snead MC , Brody RI , Jessel RH , Sestito S , Adler A , Afzal O , Gigase F , Missall R , Carrión D , Stone J , Bergink V , Dolan SM , Howell EA . Am J Obstet Gynecol MFM 2022 4 (4) 100649 BACKGROUND: Structural racism and pandemic-related stress from the COVID-19 pandemic may increase risk of adverse birth outcomes. OBJECTIVE: Our objective was to examine associations between neighborhood measures of structural racism and pandemic stress with three outcomes: SARS-CoV-2 infection, preterm birth (PTB) and delivering a newborn small-for-gestational-age (SGA). Our secondary objective was to investigate the joint associations of SARS-CoV-2 infection during pregnancy and neighborhood measures on PTB and SGA. STUDY DESIGN: We analyzed data for 967 patients from a prospective cohort of pregnant persons in New York City, comprised of 367 White persons (38%), 169 Black persons (17%), 293 Latina persons (30%), 87 Asian persons (9%), 41 persons of unknown race-ethnicity (4%), and 10 of unknown race-ethnicity (1%). We evaluated structural racism (social/built structural disadvantage, racial-economic segregation) and pandemic-related stress (community COVID-19 mortality, community unemployment rate increase) in quartiles by zip code. SARS-CoV-2 serologic enzyme-linked immunosorbent assay was performed on blood samples from pregnant persons. We ascertained preterm birth (PTB) and small-for-gestational age (SGA) from an electronic medical record database. We used log-binomial regression with robust standard error for clustering by zip code to estimate associations of each neighborhood measure separately with three outcomes: SARS-CoV-2 infection, PTB, and SGA. Covariates included maternal age, parity, insurance status, and BMI. Models with PTB and SGA as the dependent variables additionally adjusted for SARS-CoV-2 infection. RESULTS: 193 (20%) persons were SARS-CoV-2 seropositive, and the overall risk of PTB and SGA were 8.4% and 9.8%, respectively. Among birthing persons in neighborhoods in the highest quartile of structural disadvantage (n=190), 94% were non-White, 50% had public insurance, 41% were obese, 32% were seropositive, 11% delivered preterm, and 12% delivered an infant SGA. Among birthing persons in neighborhoods in the lowest quartile of structural disadvantage (n=360), 39% were non-White, 17% had public insurance, 15% were obese, 9% were seropositive, 6% delivered preterm, and 10% delivered an infant SGA. In adjusted analyses structural racism measures and community unemployment were associated with both SARS-CoV-2 infection and PTB, but not SGA. High vs. low structural disadvantage was associated with an adjusted relative risk (aRR) of 2.6 for infection (95% Confidence Interval (CI)=1.7, 3.9) and 1.7 for PTB (95%CI=1.0, 2.9); high vs. low racial-economic segregation was associated with aRR of 1.9 (95% CI=1.3, 2.8) for infection and 2.0 (95%CI=1.3, 3.2) for PTB; high vs. low community unemployment increase was associated with aRR of 1.7 (95% CI=1.2, 1.5) for infection and 1.6 (95%CI=1.0, 2.8) for PTB. COVID-19 mortality rate was associated with SARS-CoV-2 infection, but not PTB or SGA. SARS-CoV-2 infection was not independently associated with birth outcomes. We found no interaction between SARS-CoV-2 infection and neighborhood measures on PTB or SGA. CONCLUSIONS: Neighborhood measures of structural racism were associated with both SARS-CoV-2 infection and PTB, but these associations were independent and did not have a synergistic effect. Community unemployment rate increases were also associated with an increased risk of PTB independently of SARS-CoV-2 infection. Mitigating these factors might reduce the impact of the pandemic on pregnant people. |
Prevalence of neural tube defects, maternal HIV status, and antiretroviral therapy from a hospital-based birth defect surveillance in Kampala, Uganda
Barlow-Mosha L , Serunjogi R , Kalibbala D , Mumpe-Mwanja D , Williamson D , Valencia D , Tinker SC , Matovu JN , Moore CA , Adler MR , Nelson L , Nankunda J , Nabunya E , Birabwa-Male D , Musoke P . Birth Defects Res 2021 114 95-104 BACKGROUND: The estimated prevalence of neural tube defects (NTDs) in Africa is 11.7 per 10,000 live births; however, data on the impact of antiretroviral therapy (ART) during pregnancy and the risk for birth defects in Africa are limited. METHODS: Data from a hospital-based surveillance program at four hospitals in Kampala, Uganda were used to estimate the baseline prevalence of NTDs and assess potential associations with HIV status and ART use. All live births, stillbirths, and spontaneous abortions delivered at the participating hospitals affected with selected birth defects between August 2015 and December 2018 were included. Trained midwives collected data from hospital records, maternal interviews, photographs, and narrative descriptions of birth defects. We estimated NTD prevalence per 10,000 births (live, stillbirths, spontaneous abortions), prevalence ratios, and 95% confidence intervals (CIs). RESULTS: A total of 110,752 births from 107,133 women were included in the analysis; 9,394 (8.8%) women were HIV-infected and among those with HIV infection, 95.6% (n = 8,977) were on ART at delivery. Overall, 109 births were affected with NTDs, giving a prevalence of 9.8 (95% CI [8.2, 11.9]). Spina bifida (n = 63) was the most common type of NTD, with a prevalence of 5.7 (95% CI [4.4, 7.3]), followed by anencephaly (n = 31), with a prevalence of 2.8 (95% CI [2.0, 4.0]). CONCLUSION: The prevalence of NTDs among births in Kampala, Uganda is consistent with current estimates for Africa. With the continued introduction of new medications that may be taken during pregnancy, sustainable birth defect surveillance systems and pharmacovigilance are indicated. |
Developing and Validating an Effective Pediatric and Adolescent HIV Testing Eligibility Screening Tool for High-Volume Entry Points in Uganda
Katureebe C , Ashburn K , Machekano R , Gill MM , Gross J , Kazooba P , Kiyonga A , Taasi G , Adler M , Nazziwa E , Rivadeneira ED , Kekitiinwa A , Magongo E , Matovu JB , Nantume S , Bitarakwate E . J Acquir Immune Defic Syndr 2021 88 (3) 290-298 INTRODUCTION: Because of low pediatric HIV prevalence, more tests are needed to find 1 HIV-positive child compared with adults. In Uganda, the number needed to test (NNT) to find 1 new HIV-positive child was 64 in outpatient departments (OPDs) and 31 through index testing. We aimed to develop and validate a pediatric (1.5-14 years) screening tool to optimize testing approaches. METHODS: Phase 1 evaluated the performance of 10 screening questions in 14 OPDs using a variable selection algorithm to evaluate combinations of screening questions. Using logistic regression, we identified the number of screening questions with the best predictive accuracy using the receiver operation characteristic curve. Phase 2 validated the proposed tool in 15 OPDs and 7 orphan and vulnerable children programs. We estimated sensitivity, specificity, and NNT accounting for intercluster correlations. RESULTS: A total of 3482 children were enrolled. The optimal model included reported HIV-positive maternal status or 2/5 symptoms (sickly in the last 3 months, recurring skin problems, weight loss, not growing well, and history of tuberculosis). The proposed tool had sensitivity of 83.6% [95% confidence interval (CI): 68.1 to 92.4] and specificity of 62.5% (95% CI: 55.0 to 69.4). The tool was validated in a sample of 11,342 children; sensitivity was 87.8% (95% CI: 80.9 to 92.5) and specificity 62.6% (95% CI: 54.8 to 69.7) across OPDs and community sites. In OPDs, sensitivity was 88.1% (95% CI: 80.8 to 92.8) and specificity 69.0% (95% CI: 61.9 to 75.3). The NNT was 43 (95% CI: 28 to 67) across settings and 28 (95% CI: 20 to 38) for OPD. CONCLUSIONS: This HIV screening tool has high sensitivity and reasonable specificity, increasing testing efficiency and yield for children and adolescents. |
Comparison of Symptoms and RNA Levels in Children and Adults With SARS-CoV-2 Infection in the Community Setting.
Chung E , Chow EJ , Wilcox NC , Burstein R , Brandstetter E , Han PD , Fay K , Pfau B , Adler A , Lacombe K , Lockwood CM , Uyeki TM , Shendure J , Duchin JS , Rieder MJ , Nickerson DA , Boeckh M , Famulare M , Hughes JP , Starita LM , Bedford T , Englund JA , Chu HY . JAMA Pediatr 2021 175 (10) e212025 IMPORTANCE: The association between COVID-19 symptoms and SARS-CoV-2 viral levels in children living in the community is not well understood. OBJECTIVE: To characterize symptoms of pediatric COVID-19 in the community and analyze the association between symptoms and SARS-CoV-2 RNA levels, as approximated by cycle threshold (Ct) values, in children and adults. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a respiratory virus surveillance platform in persons of all ages to detect community COVID-19 cases from March 23 to November 9, 2020. A population-based convenience sample of children younger than 18 years and adults in King County, Washington, who enrolled online for home self-collection of upper respiratory samples for SARS-CoV-2 testing were included. EXPOSURES: Detection of SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) from participant-collected samples. MAIN OUTCOMES AND MEASURES: RT-PCR-confirmed SARS-CoV-2 infection, with Ct values stratified by age and symptoms. RESULTS: Among 555 SARS-CoV-2-positive participants (mean [SD] age, 33.7 [20.1] years; 320 were female [57.7%]), 47 of 123 children (38.2%) were asymptomatic compared with 31 of 432 adults (7.2%). When symptomatic, fewer symptoms were reported in children compared with adults (mean [SD], 1.6 [2.0] vs 4.5 [3.1]). Symptomatic individuals had lower Ct values (which corresponded to higher viral RNA levels) than asymptomatic individuals (adjusted estimate for children, -3.0; 95% CI, -5.5 to -0.6; P = .02; adjusted estimate for adults, -2.9; 95% CI, -5.2 to -0.6; P = .01). The difference in mean Ct values was neither statistically significant between symptomatic children and symptomatic adults (adjusted estimate, -0.7; 95% CI, -2.2 to 0.9; P = .41) nor between asymptomatic children and asymptomatic adults (adjusted estimate, -0.6; 95% CI, -4.0 to 2.8; P = .74). CONCLUSIONS AND RELEVANCE: In this community-based cross-sectional study, SARS-CoV-2 RNA levels, as determined by Ct values, were significantly higher in symptomatic individuals than in asymptomatic individuals and no significant age-related differences were found. Further research is needed to understand the role of SARS-CoV-2 RNA levels and viral transmission. |
Comparative analysis of perinatal outcomes and birth defects amongst adolescent and older Ugandan mothers: Evidence from a hospital-based surveillance database
Serunjogi R , Barlow-Mosha L , Mumpe-Mwanja D , Williamson D , Valencia D , Tinker SC , Adler MR , Namale-Matovu J , Kalibbala D , Nankunda J , Nabunya E , Birabwa-Male D , Byamugisha J , Musoke P . Reprod Health 2021 18 (1) 56 BACKGROUND: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and mothers (age 20-34 years) in four urban hospitals. METHODS: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson's chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20-34 years. RESULTS: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06-1.23), low birth weight (aOR: 1.46; CI 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02-1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12-9.13) compared to mothers 20-34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7-14.3) was statistically significant when compared to mothers 20-34 years (1.6 per 10,000 births; 95% CI 0.9-2.6). CONCLUSIONS: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20-34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population. | Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals.All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes.Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20–34 years). Adolescent mothers were more likely than mothers (20–34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20–34 years).In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions. | eng |
The Seattle Flu Study: a multiarm community-based prospective study protocol for assessing influenza prevalence, transmission and genomic epidemiology.
Chu HY , Boeckh M , Englund JA , Famulare M , Lutz B , Nickerson DA , Rieder M , Starita LM , Adler A , Brandstetter E , Frazer CD , Han PD , Gulati RK , Hadfield J , Jackson M , Kiavand A , Kimball LE , Lacombe K , Newman K , Sibley TR , Logue JK , Lyon VR , Wolf CR , Zigman Suchsland M , Shendure J , Bedford T . BMJ Open 2020 10 (10) e037295 INTRODUCTION: Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterise, and potentially contain new and emerging influenza strains at both an individual and population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population. METHODS AND ANALYSIS: Starting in the 2018-2019 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modelling platforms are in development to characterise the regional spread of influenza and other respiratory pathogens. ETHICS AND DISSEMINATION: The study was approved by the University of Washington's Institutional Review Board (STUDY00006181). Results will be disseminated through talks at conferences, peer-reviewed publications and on the study website (www.seattleflu.org). |
Cryptic transmission of SARS-CoV-2 in Washington state.
Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Huang ML , Nalla A , Pepper G , Reinhardt A , Xie H , Shrestha L , Nguyen TN , Adler A , Brandstetter E , Cho S , Giroux D , Han PD , Fay K , Frazar CD , Ilcisin M , Lacombe K , Lee J , Kiavand A , Richardson M , Sibley TR , Truong M , Wolf CR , Nickerson DA , Rieder MJ , Englund JA , Hadfield J , Hodcroft EB , Huddleston J , Moncla LH , Müller NF , Neher RA , Deng X , Gu W , Federman S , Chiu C , Duchin JS , Gautom R , Melly G , Hiatt B , Dykema P , Lindquist S , Queen K , Tao Y , Uehara A , Tong S , MacCannell D , Armstrong GL , Baird GS , Chu HY , Shendure J , Jerome KR . Science 2020 370 (6516) 571-575 Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread globally. Genome sequencing of SARS-CoV-2 allows reconstruction of its transmission history, although this is contingent on sampling. We have analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020 which subsequently spread locally before active community surveillance was implemented. |
Addressing vulnerable population needs in the last mile to the elimination of mother to child transmission of HIV: (re)claiming the HIV response for female sex workers and their children
Hakim AJ , Callahan T , Benech I , Patel M , Adler M , Modi S , Bateganya M , Parris KA , Bingham T . BMC Public Health 2020 20 (1) 1015 As countries strive to eliminate mother-to-child transmission of HIV, female sex workers (FSW) and their children still face barriers to accessing these essential services. Data on FSW uptake of HIV and reproductive health services before, during, and after pregnancy reveal inadequate service utilization. Stigma encountered by FSW in healthcare settings may contribute to low uptake of HIV testing, antiretroviral therapy (ART), and other prevention of mother-to-child HIV transmission (PMTCT) services. Coordination between community-based FSW and facility-based PMTCT programs can facilitate successful linkage of pregnant FSW to antenatal services to support PMTCT efforts. We offer a way forward to reach 90-90-90 targets for FSW and their families and eliminate mother-to-child transmission of HIV. |
Upper airways colonisation of Streptococcus pneumoniae in adults aged 60 years and older: A systematic review of prevalence and individual participant data meta-analysis of risk factors
Smith EL , Wheeler I , Adler H , Ferreira DM , Sá-Leão R , Abdullahi O , Adetifa I , Becker-Dreps S , Esposito S , Farida H , Kandasamy R , Mackenzie GA , Nuorti JP , Nzenze S , Madhi SA , Ortega O , Roca A , Safari D , Schaumburg F , Usuf E , Sanders EAM , Grant LR , Hammitt LL , O'Brien KL , Gounder P , Bruden DJT , Stanton MC , Rylance J . J Infect 2020 81 (4) 540-548 BACKGROUND: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous. METHODS: This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study. FINDINGS: Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0-39% by conventional culture methods and 3-23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26-4•21 and OR 7•72, 95% CI 1•15-51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12-2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27-2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27-0•70). INTERPRETATION: Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups. FUNDING: No funding was required. |
Bacterial septic arthritis infections associated with intra-articular injection practices for osteoarthritis knee pain - New Jersey, 2017
Ross KM , Mehr JS , Carothers BL , Greeley RD , Benowitz I , Henry D , McHugh LA , DiFedele L , Adler E , Naqvi S , Taylor L , Lifshitz E , Tan C , Montana BE . Infect Control Hosp Epidemiol 2019 40 (9) 1-6 BACKGROUND: In March 2017, the New Jersey Department of Health received reports of 3 patients who developed septic arthritis after receiving intra-articular injections for osteoarthritis knee pain at the same private outpatient facility in New Jersey. The risk of septic arthritis resulting from intra-articular injection is low. However, outbreaks of septic arthritis associated with unsafe injection practices in outpatient settings have been reported. METHODS: An infection prevention assessment of the implicated facility's practices was conducted because of the ongoing risk to public health. The assessment included an environmental inspection of the facility, staff interviews, infection prevention practice observations, and a medical record and office document review. A call for cases was disseminated to healthcare providers in New Jersey to identify patients treated at the facility who developed septic arthritis after receiving intra-articular injections. RESULTS: We identified 41 patients with septic arthritis associated with intra-articular injections. Cultures of synovial fluid or tissue from 15 of these 41 case patients (37%) recovered bacteria consistent with oral flora. The infection prevention assessment of facility practices identified multiple breaches of recommended infection prevention practices, including inadequate hand hygiene, unsafe injection practices, and poor cleaning and disinfection practices. No additional cases were identified after infection prevention recommendations were implemented by the facility. DISCUSSION: Aseptic technique is imperative when handling, preparing, and administering injectable medications to prevent microbial contamination. CONCLUSIONS: This investigation highlights the importance of adhering to infection prevention recommendations. All healthcare personnel who prepare, handle, and administer injectable medications should be trained in infection prevention and safe injection practices. |
Notes from the field: Measles outbreaks from imported cases in orthodox Jewish communities - New York and New Jersey, 2018-2019
McDonald R , Ruppert PS , Souto M , Johns DE , McKay K , Bessette N , McNulty LX , Crawford JE , Bryant P , Mosquera MC , Frontin S , Deluna-Evans T , Regenye DE , Zaremski EF , Landis VJ , Sullivan B , Rumpf BE , Doherty J , Sen K , Adler E , DiFedele L , Ostrowski S , Compton C , Rausch-Phung E , Gelman I , Montana B , Blog D , Hutton BJ , Zucker HA . MMWR Morb Mortal Wkly Rep 2019 68 (19) 444-445 On October 1, 2018, the Rockland County (New York) Department of Health (RCDOH) alerted the New York State Department of Health (NYSDOH) of an unvaccinated teenaged traveler with diagnosed measles. During the next 17 days, RCDOH learned of an additional six unvaccinated travelers with measles. On October 24, 2018, the Ocean County (New Jersey) Health Department alerted the New Jersey Department of Health (NJDOH) of a case of measles in an international traveler, with rash onset October 17. The unvaccinated travelers reported recent travel in Israel, where an outbreak of approximately 3,150 cases of measles is ongoing (1). Investigations during October 1, 2018–April 30, 2019, identified 242 laboratory-confirmed and epidemiologically linked measles cases in New York, excluding New York City, and during October 17, 2018–November 30, 2018, identified 33 in New Jersey (Figure). The cases of measles were primarily in members of orthodox Jewish communities. |
Outbreak of septic arthritis associated with intra-articular injections at an outpatient practice - New Jersey, 2017
Ross K , Mehr J , Carothers B , Greeley R , Benowitz I , McHugh L , Henry D , DiFedele L , Adler E , Naqvi S , Lifshitz E , Tan C , Montana B . MMWR Morb Mortal Wkly Rep 2017 66 (29) 777-779 On March 6, 2017, the New Jersey Department of Health (NJDOH) was notified of three cases of septic arthritis in patients who had received intra-articular injections for osteoarthritic knee pain at a private outpatient practice. The practice voluntarily closed the next day. NJDOH, in conjunction with the local health department and the New Jersey Board of Medical Examiners, conducted an investigation and identified 41 cases of septic arthritis associated with intra-articular injections administered during 250 patient visits at the same practice, including 30 (73%) patients who required surgery. Bacterial cultures of synovial fluid or tissue from 15 (37%) patients were positive; all recovered organisms were oral flora. An infection prevention assessment of the practice identified multiple breaches of recommended infection prevention practices, including inadequate hand hygiene, inappropriate use of pharmacy bulk packaged (PBP) products as multiple-dose containers and handling PBP products outside of required pharmacy conditions, and preparation of syringes up to 4 days in advance of their intended use. No additional septic arthritis cases were identified after infection prevention recommendations were implemented within the practice. |
Attrition from antiretroviral treatment services among pregnant and non-pregnant patients following adoption of Option B+ in Haiti
Domercant JW , Puttkammer N , Young P , Yuhas K , Francois K , Grand'Pierre R , Lowrance D , Adler M . Glob Health Action 2017 10 (1) 1330915 BACKGROUND: Access to antiretroviral therapy (ART) has expanded in Haiti because of the adoption of Option B+ and the revision of treatment guidelines. Retention in care and treatment varies greatly and few studies have examined retention rates, particularly among women enrolled in Option B+. OBJECTIVE: To assess attrition among pregnant and non-pregnant patients initiating ART following adoption of Option B+ in Haiti. METHODS: Longitudinal data of adult patients initiated on ART from October 2012 through August 2014 at 73 health facilities across Haiti were analyzed using a survival analysis framework to determine levels of attrition. The Kaplan-Meier method and Cox proportional hazards regression were used to examine risk factors associated with attrition. RESULTS: Among 17,059 patients who initiated ART, 7627 (44.7%) were non-pregnant women, 5899 (34.6%) were men, and 3533 (20.7%) were Option B+ clients. Attrition from the ART program was 36.7% at 12 months (95% CI: 35.9-37.5%). Option B+ patients had the highest level of attrition at 50.4% at 12 months (95% CI: 48.6-52.3%). While early HIV disease stage at ART initiation was protective among non-pregnant women and men, it was a strong risk factor among Option B+ clients. In adjusted analyses, key protective factors were older age (p < 0.0001), living near the health facility (p = 0.04), having another known HIV-positive household member (p < 0.0001), having greater body mass index (BMI) (p < 0.0001), pre-ART counseling (p < 0.0001), and Cotrimoxazole prophylaxis during baseline (p < 0.01). Higher attrition was associated with rapidly starting ART after enrollment (p < 0.0001), anemia (p < 0.0001), and regimen tenofovir+lamivudine+nevirapine (TDF+3TC+NVP) (p < 0.001). CONCLUSIONS: ART attrition in Haiti is high among adults, especially among Option B+ patients. Identifying newly initiated patients most at risk for attrition and providing appropriate interventions could help reduce ART attrition. |
Trends in prevalence of advanced HIV disease at antiretroviral therapy enrollment - 10 countries, 2004-2015
Auld AF , Shiraishi RW , Oboho I , Ross C , Bateganya M , Pelletier V , Dee J , Francois K , Duval N , Antoine M , Delcher C , Desforges G , Griswold M , Domercant JW , Joseph N , Deyde V , Desir Y , Van Onacker JD , Robin E , Chun H , Zulu I , Pathmanathan I , Dokubo EK , Lloyd S , Pati R , Kaplan J , Raizes E , Spira T , Mitruka K , Couto A , Gudo ES , Mbofana F , Briggs M , Alfredo C , Xavier C , Vergara A , Hamunime N , Agolory S , Mutandi G , Shoopala NN , Sawadogo S , Baughman AL , Bashorun A , Dalhatu I , Swaminathan M , Onotu D , Odafe S , Abiri OO , Debem HH , Tomlinson H , Okello V , Preko P , Ao T , Ryan C , Bicego G , Ehrenkranz P , Kamiru H , Nuwagaba-Biribonwoha H , Kwesigabo G , Ramadhani AA , Ng'wangu K , Swai P , Mfaume M , Gongo R , Carpenter D , Mastro TD , Hamilton C , Denison J , Wabwire-Mangen F , Koole O , Torpey K , Williams SG , Colebunders R , Kalamya JN , Namale A , Adler MR , Mugisa B , Gupta S , Tsui S , van Praag E , Nguyen DB , Lyss S , Le Y , Abdul-Quader AS , Do NT , Mulenga M , Hachizovu S , Mugurungi O , Barr BAT , Gonese E , Mutasa-Apollo T , Balachandra S , Behel S , Bingham T , Mackellar D , Lowrance D , Ellerbrock TV . MMWR Morb Mortal Wkly Rep 2017 66 (21) 558-563 Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/muL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,dagger, section sign To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence. |
Translating technical support into country action: The role of the Interagency Task Team on the Prevention and Treatment of HIV Infection in Pregnant Women, Mothers, and Children in the Global Plan era
Luo C , Hirnschall G , Rodrigues J , Romano S , Essajee S , Rogers B , McCarthy E , Mwango A , Sangrujee N , Adler MR , Houston JC , Langa JO , Urso M , Bolu O , Tene G , Elat Nfetam JB , Kembou E , Phelps BR . J Acquir Immune Defic Syndr 2017 75 Suppl 1 S7-s16 While the Interagency Task Team on the Prevention and Treatment of HIV Infection in Pregnant Women, Mothers, and Children (IATT) partnership existed before the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), its reconfiguration was critical to coordinating provision of technical assistance that positively influenced country decision-making and program performance. This article describes how the Global Plan anchored the work of the IATT and, in turn, how the IATT's technical assistance helped to accelerate achievement of the Global Plan targets and milestones. The technical assistance that will be discussed addressed a broad range of priority actions and milestones described in the Global Plan: (1) planning for and implementing Option B+; (2) strengthening monitoring and evaluation systems; (3) translating evidence into action and advocacy; and (4) promoting community engagement. This article also reviews the ongoing challenges and opportunities of providing technical assistance in a rapidly evolving environment that calls for ever more flexible and contextualized responses. The effectiveness of technical assistance facilitated by the IATT was defined by its timeliness, evidence base, and unique global perspective that built on the competencies of its partners and promoted synergies across program areas. Reaching the final goal of eliminating vertical transmission of HIV infection and achieving an AIDS-free generation in countries with the highest HIV burden requires that the IATT partnership and technical assistance remain responsive to country-specific needs while aligning with the current programmatic reality and new global goals such as the Sustainable Development Goals and 90-90-90 targets. |
Confronting challenges in monitoring and evaluation: Innovation in the context of the Global Plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive
Radin AK , Abutu AA , Okwero MA , Adler MR , Anyaike C , Asiimwe HT , Behumbiize P , Efuntoye TA , King RL , Kisaakye LN , Ogundehin DT , Phelps BR , Watts H , Weissglas F . J Acquir Immune Defic Syndr 2017 75 Suppl 1 S66-s75 The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), which was launched in 2011, set a series of ambitious targets, including a reduction of new HIV infections among children by 90% by 2015 (from a baseline year of 2009) and AIDS-related maternal mortality by 50% by 2015. To reach these targets, the Global Plan called for unprecedented investments in the prevention of mother-to-child transmission of HIV (PMTCT), innovative new approaches to service delivery, immense collective effort on the programmatic and policy fronts, and importantly, a renewed focus on data collection and use. We provide an overview of major achievements in monitoring and evaluation across Global Plan countries and highlight key challenges and innovative country-driven solutions using PMTCT program data. Specifically, we describe the following: (1) Uganda's development and use of a weekly reporting system for PMTCT using short message service technology that facilitates real-time monitoring and programmatic adjustments throughout the transition to a "treat all" approach for pregnant and breastfeeding women living with HIV (Option B+); (2) Uganda's work to eliminate parallel reporting systems while strengthening the national electronic district health information system; and (3) how routine PMTCT program data in Nigeria can be used to estimate HIV prevalence at the local level and address a critical gap in local descriptive epidemiologic data to better target limited resources. We also identify several ongoing challenges in data collection, analysis, and use, and we suggest potential solutions. |
ART attrition and risk factors among Option B+ patients in Haiti: A retrospective cohort study
Puttkammer N , Domercant JW , Adler M , Yuhas K , Myrtil M , Young P , Francois K , Grand'Pierre R , Lowrance D . PLoS One 2017 12 (3) e0173123 OBJECTIVES: In October 2012, the Haitian Ministry of Health endorsed the "Option B+" strategy to eliminate mother-to-child transmission of HIV and achieve HIV epidemic control. The objective of this paper is to assess and identify risk factors for attrition from the national ART program among Option B+ patients in the 12 months after ART initiation. DESIGN: This retrospective cohort study included patients newly initiating ART from October 2012-August 2013 at 68 ART sites covering 45% of all newly enrolled ART patients in all regions of Haiti. METHODS: With data from electronic medical records, we carried out descriptive analysis of sociodemographic, clinical, and pregnancy-related correlates of ART attrition, and used a modified Poisson regression approach to estimate relative risks in a multivariable model. RESULTS: There were 2,166 Option B+ patients who initiated ART, of whom 1,023 were not retained by 12 months (47.2%). One quarter (25.3%) dropped out within 3 months of ART initiation. Protective factors included older age, more advanced HIV disease progression, and any adherence counseling prior to ART initiation, while risk factors included starting ART late in gestation, starting ART within 7 days of HIV testing, and using an atypical ART regimen. DISCUSSION: Our study demonstrates early ART attrition among Option B+ patients and contributes evidence on the characteristics of women who are most at risk of attrition in Haiti. Our findings highlight the importance of targeted strategies to support retention among Option B+ patients. |
What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira.
Fouts DE , Matthias MA , Adhikarla H , Adler B , Amorim-Santos L , Berg DE , Bulach D , Buschiazzo A , Chang YF , Galloway RL , Haake DA , Haft DH , Hartskeerl R , Ko AI , Levett PN , Matsunaga J , Mechaly AE , Monk JM , Nascimento AL , Nelson KE , Palsson B , Peacock SJ , Picardeau M , Ricaldi JN , Thaipandungpanit J , Wunder EA Jr , Yang XF , Zhang JJ , Vinetz JM . PLoS Negl Trop Dis 2016 10 (2) e0004403 Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non-infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious Leptospira, this work provides new insights into the evolution of a genus of bacterial pathogens. This work will be a comprehensive roadmap for understanding leptospirosis pathogenesis. More generally, it provides new insights into mechanisms by which bacterial pathogens adapt to mammalian hosts. |
Vital Signs: estimated effects of a coordinated approach for action to reduce antibiotic-resistant infections in health care facilities - United States
Slayton RB , Toth D , Lee BY , Tanner W , Bartsch SM , Khader K , Wong K , Brown K , McKinnell JA , Ray W , Miller LG , Rubin M , Kim DS , Adler F , Cao C , Avery L , Stone NT , Kallen A , Samore M , Huang SS , Fridkin S , Jernigan JA . MMWR Morb Mortal Wkly Rep 2015 64 (30) 826-31 BACKGROUND: Treatments for health care-associated infections (HAIs) caused by antibiotic-resistant bacteria and Clostridium difficile are limited, and some patients have developed untreatable infections. Evidence-supported interventions are available, but coordinated approaches to interrupt the spread of HAIs could have a greater impact on reversing the increasing incidence of these infections than independent facility-based program efforts. METHODS: Data from CDC's National Healthcare Safety Network and Emerging Infections Program were analyzed to project the number of health care-associated infections from antibiotic-resistant bacteria or C. difficile both with and without a large scale national intervention that would include interrupting transmission and improved antibiotic stewardship. As an example, the impact of reducing transmission of one antibiotic-resistant infection (carbapenem-resistant Enterobacteriaceae [CRE]) on cumulative prevalence and number of HAI transmission events within interconnected groups of health care facilities was modeled using two distinct approaches, a large scale and a smaller scale health care network. RESULTS: Immediate nationwide infection control and antibiotic stewardship interventions, over 5 years, could avert an estimated 619,000 HAIs resulting from CRE, multidrug-resistant Pseudomonas aeruginosa, invasive methicillin-resistant Staphylococcus aureus (MRSA), or C. difficile. Compared with independent efforts, a coordinated response to prevent CRE spread across a group of inter-connected health care facilities resulted in a cumulative 74% reduction in acquisitions over 5 years in a 10-facility network model, and 55% reduction over 15 years in a 102-facility network model. CONCLUSIONS: With effective action now, more than half a million antibiotic-resistant health care-associated infections could be prevented over 5 years. Models representing both large and small groups of interconnected health care facilities illustrate that a coordinated approach to interrupting transmission is more effective than historical independent facilitybased efforts. IMPLICATIONS FOR PUBLIC HEALTH: Public health-led coordinated prevention approaches have the potential to more completely address the emergence and dissemination of these antibiotic-resistant organisms and C. difficile than independent facility-based efforts. |
Introduction of rapid syphilis testing in antenatal care: a systematic review of the impact on HIV and syphilis testing uptake and coverage
Swartzendruber A , Steiner RJ , Adler MR , Kamb ML , Newman LM . Int J Gynaecol Obstet 2015 130 Suppl 1 S15-21 BACKGROUND: Global guidelines recommend universal syphilis and HIV screening for pregnant women. Rapid syphilis testing (RST) may contribute toward achievement of universal screening. OBJECTIVES: To examine the impact of RST on syphilis and HIV screening among pregnant women. SEARCH STRATEGY: We searched MEDLINE for English- and non-English language articles published through November, 2014. SELECTION CRITERIA: We included studies that used a comparative design and reported on syphilis and HIV test uptake among pregnant women in low- and middle-income countries (LMICs) following introduction of RST. DATA COLLECTION AND ANALYSIS: Data were extracted from six eligible articles presenting findings from Asia, Africa, and Latin America. MAIN RESULTS: All studies reported substantial increases in antenatal syphilis testing following introduction of RST; the latter did not appear to adversely impact antenatal HIV screening levels at sites already offering rapid HIV testing and may increase HIV screening among pregnant women in some settings. Qualitative data revealed that women were highly satisfied with RST. Nevertheless, ensuring adequate training for healthcare workers and supplies of commodities were cited as key implementation barriers. CONCLUSIONS: RST may increase antenatal syphilis and HIV screening and contribute to the improvement of antenatal care in LMICs. |
Isolation of Onchocerca lupi in dogs and black flies, California, USA
Hassan HK , Bolcen S , Kubofcik J , Nutman TB , Eberhard ML , Middleton K , Wekesa JW , Ruedas G , Nelson KJ , Dubielzig R , De Lombaert M , Silverman B , Schorling JJ , Adler PH , Unnasch TR , Beeler ES . Emerg Infect Dis 2015 21 (5) 789-96 In southern California, ocular infections caused by Onchocerca lupi were diagnosed in 3 dogs (1 in 2006, 2 in 2012). The infectious agent was confirmed through morphologic analysis of fixed parasites in tissues and by PCR and sequencing of amplicons derived from 2 mitochondrially encoded genes and 1 nuclear-encoded gene. A nested PCR based on the sequence of the cytochrome oxidase subunit 1 gene of the parasite was developed and used to screen Simulium black flies collected from southern California for O. lupi DNA. Six (2.8%; 95% CI 0.6%-5.0%) of 213 black flies contained O. lupi DNA. Partial mitochondrial16S rRNA gene sequences from the infected flies matched sequences derived from black fly larvae cytotaxonomically identified as Simulium tribulatum. These data implicate S. tribulatum flies as a putative vector for O. lupi in southern California. |
Classification of Leptospira genomospecies 1, 3, 4 and 5 as Leptospira alstonii sp. nov., Leptospira vanthielii sp. nov., Leptospira terpstrae sp. nov. and Leptospira yanagawae sp. nov., respectively
Smythe L , Adler B , Hartskeerl RA , Galloway RL , Turenne CY , Levett PN . Int J Syst Evol Microbiol 2013 63 1859-62 The genus Leptospira currently comprises 16 named species. In addition, four unnamed hybridization groups were designated Leptospira genomospecies 1, 3, 4 and 5. These groups represent valid species-level taxa, but were not assigned names in the original description by Brenner et al. [Int J Syst Bacteriol 49, 839-858 (1999)]. To rectify this situation, it is proposed that Leptospira genomospecies 1, genomospecies 3, genomospecies 4 and genomospecies 5 should be classified as Leptospira alstonii sp. nov., Leptospira vanthielii sp. nov., Leptospira terpstrae sp. nov. and Leptospira yanagawae sp. nov., respectively, with strains L. alstonii 79601(T) ( = ATCC BAA-2439(T)), L. vanthielii WaZ Holland(T) ( = ATCC 700522(T)), L. terpstrae LT 11-33(T) ( = ATCC 700639(T)) and L. yanagawae Sao Paulo(T) ( = ATCC 700523(T)) as the type strains. The type strains are also available from the culture collections of the WHO Collaborating Centres in Amsterdam, The Netherlands, and Brisbane, Australia. |
PMTCT Option B+: an opportunity for shaping a new service delivery paradigm
Riley PL , Adler MR , Davis MK . Afr J Midwifery Womens Health 2013 7 (1) 6-6 In 2011, the Joint United Nations | Programme on HIV/AIDS (UNAIDS) | and the US Office of the Global AIDS | Coordinator—the office charged with implementing the President’s Emergency Plan for | AIDS Relief (PEPFAR), launched a 4-year | Global Plan Toward the Elimination of New | HIV Infections Among Children by 2015, and | Keeping their Mothers Alive (UNAIDS, 2011). | Focusing on the 22 countries with the highest number of HIV positive pregnant women | globally, this initiative promotes a range of | HIV and maternal, newborn, and child health | (MNCH) interventions aimed at decreasing | new HIV infections among children by 90% | and reducing HIV-related maternal mortality by 50%. The Global Plan emphasises | HIV prevention through timely initiation of | antiretroviral therapy (ART) for pregnant and | breastfeeding mothers, early diagnosis of HIV | exposed infants, and treatment for those who | become HIV infected. The overlap in the timing and frequency of these HIV services with | MNCH interventions, including immunisations, infant feeding support, and family planning, underscores the need for greater synergy | between these programmes. |
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