Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-26 (of 26 Records) |
Query Trace: Deming M[original query] |
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Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci.
Eriksen HB , Fuursted K , Jensen A , Jensen CS , Nielsen X , Christensen JJ , Shewmaker P , Rebelo AR , Aarestrup FM , Schønning K , Slotved HC . Front Microbiol 2023 14 1120023 INTRODUCTION: For Streptococcus pneumoniae, β-lactam susceptibility can be predicted from the amino acid sequence of the penicillin-binding proteins PBP1a, PBP2b, and PBP2x. The combination of PBP-subtypes provides a PBP-profile, which correlates to a phenotypic minimal inhibitory concentration (MIC). The non-S. pneumoniae Mitis-group streptococci (MGS) have similar PBPs and exchange pbp-alleles with S. pneumoniae. We studied whether a simple BLAST analysis could be used to predict phenotypic susceptibility in Danish S. pneumoniae isolates and in internationally collected MGS. METHOD: Isolates with available WGS and phenotypic susceptibility data were included. For each isolate, the best matching PBP-profile was identified by BLAST analysis. The corresponding MICs for penicillin and ceftriaxone was retrieved. Category agreement (CA), minor-, major-, and very major discrepancy was calculated. Genotypic-phenotypic accuracy was examined with Deming regression. RESULTS: Among 88 S. pneumoniae isolates, 55 isolates had a recognized PBP-profile, and CA was 100% for penicillin and 98.2% for ceftriaxone. In 33 S. pneumoniae isolates with a new PBP-profile, CA was 90.9% (penicillin) and 93.8% (ceftriaxone) using the nearest recognized PBP-profile. Applying the S. pneumoniae database to non-S. pneumoniae MGS revealed that none had a recognized PBP-profile. For Streptococcus pseudopneumoniae, CA was 100% for penicillin and ceftriaxone in 19 susceptible isolates. In 33 Streptococcus mitis isolates, CA was 75.8% (penicillin) and 86.2% (ceftriaxone) and in 25 Streptococcus oralis isolates CA was 8% (penicillin) and 100% (ceftriaxone). CONCLUSION: Using a simple BLAST analysis, genotypic susceptibility prediction was accurate in Danish S. pneumoniae isolates, particularly in isolates with recognized PBP-profiles. Susceptibility was poorly predicted in other MGS using the current database. |
Skin Metagenomic Sequence Analysis of Early Candida auris Outbreaks in U.S. Nursing Homes.
Huang X , Welsh RM , Deming C , Proctor DM , Thomas PJ , Gussin GM , Huang SS , Kong HH , Bentz ML , Vallabhaneni S , Chiller T , Jackson BR , Forsberg K , Conlan S , Litvintseva AP , Segre JA . mSphere 2021 6 (4) e0028721 Candida auris is a human fungal pathogen classified as an urgent threat to the delivery of health care due to its extensive antimicrobial resistance and the high mortality rates associated with invasive infections. Global outbreaks have occurred in health care facilities, particularly, long-term care hospitals and nursing homes. Skin is the primary site of colonization for C. auris. To accelerate research studies, we developed microbiome sequencing protocols, including amplicon and metagenomic sequencing, directly from patient samples at health care facilities with ongoing C. auris outbreaks. We characterized the skin mycobiome with a database optimized to classify Candida species and C. auris to the clade level. While Malassezia species were the predominant skin-associated fungi, nursing home residents also harbored Candida species, including C. albicans, and C. parapsilosis. Amplicon sequencing was concordant with culturing studies to identify C. auris-colonized patients and provided further resolution that distinct clades of C. auris are colonizing facilities in New York and Illinois. Shotgun metagenomic sequencing from a clinical sample with a high fungal bioburden generated a skin-associated profile of the C. auris genome. Future larger scale clinical studies are warranted to more systematically investigate the effects of commensal microbes and patient risk factors on the colonization and transmission of C. auris. IMPORTANCE Candida auris is a human pathogen of high concern due to its extensive antifungal drug resistance and high mortality rates associated with invasive infections. Candida auris skin colonization and persistence on environmental surfaces make this pathogen difficult to control once it enters a health care facility. Residents in long-term care hospitals and nursing homes are especially vulnerable. In this study, we developed microbiome sequencing protocols directly from surveillance samples, including amplicon and metagenomic sequencing, demonstrating concordance between sequencing results and culturing. |
Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility.
Proctor DM , Dangana T , Sexton DJ , Fukuda C , Yelin RD , Stanley M , Bell PB , Baskaran S , Deming C , Chen Q , Conlan S , Park M , Welsh RM , Vallabhaneni S , Chiller T , Forsberg K , Black SR , Pacilli M , Kong HH , Lin MY , Schoeny ME , Litvintseva AP , Segre JA , Hayden MK . Nat Med 2021 27 (8) 1401-1409 Candida auris is a fungal pathogen of high concern due to its ability to cause healthcare-associated infections and outbreaks, its resistance to antimicrobials and disinfectants and its persistence on human skin and in the inanimate environment. To inform surveillance and future mitigation strategies, we defined the extent of skin colonization and explored the microbiome associated with C. auris colonization. We collected swab specimens and clinical data at three times points between January and April 2019 from 57 residents (up to ten body sites each) of a ventilator-capable skilled nursing facility with endemic C. auris and routine chlorhexidine gluconate (CHG) bathing. Integrating microbial-genomic and epidemiologic data revealed occult C. auris colonization of multiple body sites not targeted commonly for screening. High concentrations of CHG were associated with suppression of C. auris growth but not with deleterious perturbation of commensal microbes. Modeling human mycobiome dynamics provided insight into underlying alterations to the skin fungal community as a possible modifiable risk factor for acquisition and persistence of C. auris. Failure to detect the extensive, disparate niches of C. auris colonization may reduce the effectiveness of infection-prevention measures that target colonized residents, highlighting the importance of universal strategies to reduce C. auris transmission. |
Folate Forms in RBC and Whole-Blood Lysates Appear Stable When Stored Frozen for 2 Years
Fazili Z , Paladugula N , Zhang M , Pfeiffer CM . J Nutr 2021 151 (9) 2852-2860 BACKGROUND: The use of RBC lysate (RBC-Lys) eliminates the need for serum folate and hematocrit (Hct) measurement to calculate RBC folate. Information on the long-term frozen storage stability of RBC-Lys is missing. OBJECTIVES: We aimed to assess the comparability of RBC folate forms in whole-blood lysate (WB-Lys) and RBC-Lys and the folate stability in both matrices. METHODS: We prepared conventional WB-Lys (1:11 dilution with 1% ascorbic acid) and RBC-Lys (1:11 dilution of washed and saline-diluted RBCs with 1% ascorbic acid) from EDTA blood (n = 60 adult donors) and stored lysates at -70°C until analysis at baseline (1 wk), 3, 6, 12, and 24 mo. Before analysis by HPLC-tandem MS, we incubated the WB-Lys (4 h at 37°C) and treated the RBC-Lys with human recombinant γ-glutamyl hydrolase for folate polyglutamate deconjugation. We analyzed RBC-Lys samples for hemoglobin (Hb) (same aliquot) to normalize for the preanalytical dilution; Hb-folate was converted to RBC folate for each folate form using the mean corpuscular Hb concentration. We analyzed Hct as well as folate forms in matching serum samples for traditional RBC folate calculation. We conducted descriptive data analyses (correlation, Bland-Altman plot, Deming regression). RESULTS: At baseline, results for RBC folate forms derived from WB-Lys compared with RBC-Lys samples showed excellent correlation (Pearson r ≥ 0.97). Mean ± SD concentrations compared well for total folate (WB-Lys: 886 ± 255 compared with RBC-Lys: 899 ± 271 nmol/L), 5-methyltetrahydrofolate (WB-Lys: 831 ± 258 compared with RBC-Lys: 843 ± 276 nmol/L), and nonmethyl folate (WB-Lys: 53.3 ± 74.4 compared with RBC-Lys: 52.9 ± 70.7 nmol/L), but were 17% higher in RBC-Lys for pyrazino-s-triazine derivative of 4α-hydroxy-5-CH3-H4folate (MeFox) (WB-Lys: 147 ± 44.1 compared with RBC-Lys: 172 ± 53.5 nmol/L). Frozen storage of WB-Lys and RBC-Lys samples for ≤24 mo showed ≤5%, ≤5%, ≤13%, and ≤11% change in total folate, 5-methyltetrahydrofolate, nonmethyl folate, and MeFox, respectively. CONCLUSIONS: Erythrocyte folate forms appear to be stable in RBC-Lys samples stored frozen at -70°C for ≤2 y. The relatively small changes in folate concentrations over time were comparable between RBC-Lys and conventionally prepared WB-Lys samples. |
Evolution of the monitoring and evaluation strategies to support the World Health Organization's Global Programme to Eliminate Lymphatic Filariasis
Lammie PJ , Gass KM , King J , Deming MS , Addiss DG , Biswas G , Ottesen EA , Henderson R . Int Health 2020 13 S65-s70 The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established with the ambitious goal of eliminating LF as a public health problem. The remarkable success of the GPELF over the past 2 decades in carrying out its principal strategy of scaling up and scaling down mass drug administration has relied first on the development of a rigorous monitoring and evaluation (M&E) framework and then the willingness of the World Health Organization and its community of partners to modify this framework in response to the practical experiences of national programmes. This flexibility was facilitated by the strong partnership that developed among researchers, LF programme managers and donors willing to support the necessary research agenda. This brief review summarizes the historical evolution of the GPELF M&E strategies and highlights current research needed to achieve the elimination goal. |
Immunogenicity of seasonal inactivated influenza and inactivated polio vaccines among children in Senegal: Results from a cluster-randomized trial
Niang M , Deming ME , Goudiaby D , Diop OM , Dia N , Diallo A , Ortiz JR , Diop D , Lewis KDC , Lafond KE , Widdowson MA , Victor JC , Neuzil KM . Vaccine 2020 38 (47) 7526-7532 Data on influenza vaccine immunogenicity in children are limited from tropical developing countries. We recently reported significant, moderate effectiveness of a trivalent inactivated influenza vaccine (IIV) in a controlled, cluster-randomized trial in children in rural Senegal during 2009, a year of H3N2 vaccine mismatch (NCT00893906). We report immunogenicity of IIV3 and inactivated polio vaccine (IPV) from that trial. We evaluated hemagglutination inhibition (HAI) and polio antibody titers in response to vaccination of three age groups (6 through 35 months, 3 through 5 years, and 6 through 8 years). As all children were IIV naïve, each received two vaccine doses, although titers were assessed after only the first dose for subjects aged 6 through 8 years. Seroconversion rates (4-fold titer rise or increase from <1:10 to ≥1:40) were 74-87% for A/H1N1, 76-87% for A/H3N2, and 54-79% for B/Yamagata. Seroprotection rates (HAI titer ≥ 1:40) were 79-88% for A/H1N1, 88-96% for A/H3N2, and 52-74% for B/Yamagata. IIV responses were lowest in the youngest age group, and they were comparable between ages 3 through 5 years after two doses and 6 through 8 years after one dose. We found that baseline seropositivity (HAI titer ≥ 1:10) was an effect modifier of IIV response. Using a seroprotective titer (HAI titer ≥ 1:160) recommended for IIV evaluation in children, we found that among subjects who were seropositive at baseline, 69% achieved seroprotection for both A/H1N1 and A/H3N2, while among those who were seronegative at baseline, seroprotection was achieved in 11% for A/H1N1 and 22% for A/H3N2. The IPV group had high baseline polio antibody seropositivity and appropriate responses to vaccination. Our data emphasize the importance of a two-dose IIV3 series in vaccine naïve children. IIV and IPV vaccines were immunogenic in Senegalese children. |
Investigation of a Cluster of Sphingomonas koreensis Infections.
Johnson RC , Deming C , Conlan S , Zellmer CJ , Michelin AV , Lee-Lin S , Thomas PJ , Park M , Weingarten RA , Less J , Dekker JP , Frank KM , Musser KA , McQuiston JR , Henderson DK , Lau AF , Palmore TN , Segre JA . N Engl J Med 2018 379 (26) 2529-2539 BACKGROUND: Plumbing systems are an infrequent but known reservoir for opportunistic microbial pathogens that can infect hospitalized patients. In 2016, a cluster of clinical sphingomonas infections prompted an investigation. METHODS: We performed whole-genome DNA sequencing on clinical isolates of multidrug-resistant Sphingomonas koreensis identified from 2006 through 2016 at the National Institutes of Health (NIH) Clinical Center. We cultured S. koreensis from the sinks in patient rooms and performed both whole-genome and shotgun metagenomic sequencing to identify a reservoir within the infrastructure of the hospital. These isolates were compared with clinical and environmental S. koreensis isolates obtained from other institutions. RESULTS: The investigation showed that two isolates of S. koreensis obtained from the six patients identified in the 2016 cluster were unrelated, but four isolates shared more than 99.92% genetic similarity and were resistant to multiple antibiotic agents. Retrospective analysis of banked clinical isolates of sphingomonas from the NIH Clinical Center revealed the intermittent recovery of a clonal strain over the past decade. Unique single-nucleotide variants identified in strains of S. koreensis elucidated the existence of a reservoir in the hospital plumbing. Clinical S. koreensis isolates from other facilities were genetically distinct from the NIH isolates. Hospital remediation strategies were guided by results of microbiologic culturing and fine-scale genomic analyses. CONCLUSIONS: This genomic and epidemiologic investigation suggests that S. koreensis is an opportunistic human pathogen that both persisted in the NIH Clinical Center infrastructure across time and space and caused health care-associated infections. (Funded by the NIH Intramural Research Programs.). |
CD4 lymphocyte enumeration and hemoglobin assessment aid for priority decisions: a multisite evaluation of the BD FACSPresto System
Thakar M , Angira F , Pattanapanyasat K , Wu AHB , O'Gorman M , Zeng H , Qu C , Mahajan B , Sukapirom K , Chen D , Hao Y , Gong Y , Indig MA , Graminske S , Orta D , d'Empaire N , Lu B , Omana-Zapata I , Zeh C . Open AIDS J 2017 11 76-90 Background: The BD FACSPresto system uses capillary and venous blood to measure CD4 absolute counts (CD4), %CD4 in lymphocytes, and hemoglobin (Hb) in approximately 25 minutes. CD4 cell count is used with portable CD4 counters in resource-limited settings to manage HIV/AIDS patients. A method comparison was performed using capillary and venous samples from seven clinical laboratories in five countries. The BD FACSPresto system was assessed for variability between laboratory, instrument/operators, cartridge lots and within-run at four sites. Methods: Samples were collected under approved voluntary consent. EDTA-anticoagulated venous samples were tested for CD4 and %CD4 T cells using the gold-standard BD FACSCalibur() system, and for Hb, using the Sysmex((R)) KX-21N() analyzer. Venous and capillary samples were tested on the BD FACSPresto system. Matched data was analyzed for bias (Deming linear regression and Bland-Altman methods), and for concordance around the clinical decision point. The coefficient of variation was estimated per site, instrument/operator, cartridge-lot and between-runs. Results: For method comparison, 93% of the 720 samples were from HIV-positive and 7% from HIV-negative or normal subjects. CD4 and %CD4 T cells venous and capillary results gave slopes within 0.96-1.05 and R(2) >/=0.96; Hb slopes were >/=1.00 and R(2) >/=0.89. Variability across sites/operators gave %CV <5.8% for CD4 counts, <1.9% for %CD4 and <3.2% for Hb. The total %CV was <7.7% across instrument/cartridge lot. Conclusion: The BD FACSPresto system provides accurate, reliable, precise CD4/%CD4/Hb results compared to gold-standard methods, irrespective of venous or capillary blood sampling. The data showed good agreement between the BD FACSPresto, BD FACSCalibur and Sysmex systems. |
Clinical evaluation of the BD FACSPresto Near-Patient CD4 Counter in Kenya
Angira F , Akoth B , Omolo P , Opollo V , Bornheimer S , Judge K , Tilahun H , Lu B , Omana-Zapata I , Zeh C . PLoS One 2016 11 (8) e0157939 BACKGROUND: The BD FACSPresto Near-Patient CD4 Counter was developed to expand HIV/AIDS management in resource-limited settings. It measures absolute CD4 counts (AbsCD4), percent CD4 (%CD4), and hemoglobin (Hb) from a single drop of capillary or venous blood in approximately 23 minutes, with throughput of 10 samples per hour. We assessed the performance of the BD FACSPresto system, evaluating accuracy, stability, linearity, precision, and reference intervals using capillary and venous blood at KEMRI/CDC HIV-research laboratory, Kisumu, Kenya, and precision and linearity at BD Biosciences, California, USA. METHODS: For accuracy, venous samples were tested using the BD FACSCalibur instrument with BD Tritest CD3/CD4/CD45 reagent, BD Trucount tubes, and BD Multiset software for AbsCD4 and %CD4, and the Sysmex KX-21N for Hb. Stability studies evaluated duration of staining (18-120-minute incubation), and effects of venous blood storage <6-24 hours post-draw. A normal cohort was tested for reference intervals. Precision covered multiple days, operators, and instruments. Linearity required mixing two pools of samples, to obtain evenly spaced concentrations for AbsCD4, total lymphocytes, and Hb. RESULTS: AbsCD4 and %CD4 venous/capillary (N = 189/ N = 162) accuracy results gave Deming regression slopes within 0.97-1.03 and R2 ≥0.96. For Hb, Deming regression results were R2 ≥0.94 and slope ≥0.94 for both venous and capillary samples. Stability varied within 10% 2 hours after staining and for venous blood stored less than 24 hours. Reference intervals results showed that gender-but not age-differences were statistically significant (p<0.05). Precision results had <3.5% coefficient of variation for AbsCD4, %CD4, and Hb, except for low AbsCD4 samples (<6.8%). Linearity was 42-4,897 cells/muL for AbsCD4, 182-11,704 cells/muL for total lymphocytes, and 2-24 g/dL for Hb. CONCLUSIONS: The BD FACSPresto system provides accurate, precise clinical results for capillary or venous blood samples and is suitable for near-patient CD4 testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT02396355. |
Tetanus immunity among women aged 15-39 years in Cambodia: A national population-based serosurvey, 2012
Scobie HM , Mao B , Buth S , Wannemuehler KA , Sorensen C , Kannarath C , Jenks MH , Moss DM , Priest JW , Soeung SC , Deming MS , Lammie PJ , Gregory CJ . Clin Vaccine Immunol 2016 23 (7) 546-54 INTRODUCTION: To monitor progress toward maternal and neonatal tetanus elimination (MNTE) in Cambodia, we conducted a nationwide serosurvey of tetanus immunity in 2012. METHODS: Multi-stage cluster sampling was used to select 2,154 women aged 15-39 years. Tetanus toxoid antibodies in sera were measured by gold-standard double antigen ELISA (DAE) and a novel multiplex bead assay (MBA). Antibody concentrations ≥0.01 IU/ml by DAE, or equivalent for MBA, were considered seroprotective. RESULTS: Estimated tetanus seroprotection was 88% (95% CI: 86%-89%); 64% (95% CI: 61%-67%) of women had antibody levels ≥1.0 IU/ml. Seroprotection was significantly lower (p <0.001) among women aged 15-19 years (63%) and 20-24 years (87%) compared with ≥25 years (96%), nulliparous compared with parous (71% vs. 97%), and living in the west compared with other regions (82% vs. 89%). The MBA showed high sensitivity (99% [95% CI: 98%-99%]) and specificity (92% [95% CI: 88%-95%]) compared with DAE. CONCLUSIONS: Findings were compatible with MNTE in Cambodia (≥80% protection). Tetanus immunity gaps should be addressed through strengthened routine immunization and targeted vaccination campaigns. Incorporating tetanus testing in national serosurveys using MBAs, which can measure immunity to multiple pathogens simultaneously, may be beneficial for monitoring MNTE. |
Spatial variation of insecticide resistance in the dengue vector Aedes aegypti presents unique vector control challenges
Deming R , Manrique-Saide P , Medina Barreiro A , Cardena EU , Che-Mendoza A , Jones B , Liebman K , Vizcaino L , Vazquez-Prokopec G , Lenhart A . Parasit Vectors 2016 9 (1) 67 BACKGROUND: Dengue is a major public health problem in Mexico, where the use of chemical insecticides to control the principal dengue vector, Aedes aegypti, is widespread. Resistance to insecticides has been reported in multiple sites, and the frequency of kdr mutations associated with pyrethroid resistance has increased rapidly in recent years. In the present study, we characterized patterns of insecticide resistance in Ae. aegypti populations in five small towns surrounding the city of Merida, Mexico. METHODS: A cross-sectional, entomological survey was performed between June and August 2013 in 250 houses in each of the five towns. Indoor resting adult mosquitoes were collected in all houses and four ovitraps were placed in each study block. CDC bottle bioassays were conducted using F0-F2 individuals reared from the ovitraps and kdr allele (Ile1016 and Cys1534) frequencies were determined. RESULTS: High, but varying, levels of resistance to chorpyrifos-ethyl was detected in all study towns, complete susceptibility to bendiocarb in all except one town, and variations in resistance to deltamethrin between towns, ranging from 63-88 % mortality. Significant associations were detected between deltamethrin resistance and the presence of both kdr alleles. Phenotypic resistance was highly predictive of the presence of both alleles, however, not all mosquitoes containing a mutant allele were phenotypically resistant. An analysis of genotypic differentiation (exact G test) between the five towns based on the adult female Ae. aegypti collected from inside houses showed highly significant differences (p < 0.0001) between genotypes for both loci. When this was further analyzed to look for fine scale differences at the block level within towns, genotypic differentiation was significant for both loci in San Lorenzo (Ile1016, p = 0.018 and Cys1534, p = 0.007) and for Ile1016 in Acanceh (p = 0.013) and Conkal (p = 0.031). CONCLUSIONS: The results from this study suggest that 3 years after switching chemical groups, deltamethrin resistance and a high frequency of kdr alleles persisted in Ae. aegypti populations. The spatial variation that was detected in both resistance phenotypes and genotypes has practical implications, both for vector control operations as well as insecticide resistance management strategies. |
Accuracy of coverage survey recall following an integrated mass drug administration for Lymphatic Filariasis, Schistosomiasis, and soil-transmitted Helminthiasis
Budge PJ , Sognikin E , Akosa A , Mathieu EM , Deming M . PLoS Negl Trop Dis 2016 10 (1) e0004358 BACKGROUND: Achieving target coverage levels for mass drug administration (MDA) is essential to elimination and control efforts for several neglected tropical diseases (NTD). To ensure program goals are met, coverage reported by drug distributors may be validated through household coverage surveys that rely on respondent recall. This is the first study to assess accuracy in such surveys. METHODOLOGY/PRINCIPAL FINDINGS: Recall accuracy was tested in a series of coverage surveys conducted at 1, 6, and 12 months after an integrated MDA in Togo during which three drugs (albendazole, ivermectin, and praziquantel) were distributed. Drug distribution was observed during the MDA to ensure accurate recording of persons treated during the MDA. Information was obtained for 506, 1131, and 947 persons surveyed at 1, 6, and 12 months, respectively. Coverage (defined as the percentage of persons taking at least one of the MDA medications) within these groups was respectively 88.3%, 87.4%, and 80.0%, according to the treatment registers; it was 87.9%, 91.4% and 89.4%, according to survey responses. Concordance between respondents and registers on swallowing at least one pill was >95% at 1 month and >86% at 12 months; the lower concordance at 12 months was more likely due to difficulty matching survey respondents with the year-old treatment register rather than inaccurate responses. Respondents generally distinguished between pills similar in appearance; concordance for recall of which pills were taken was over 80% in each survey. SIGNIFICANCE: In this population, coverage surveys provided remarkably consistent coverage estimates for up to one year following an integrated MDA. It is not clear if similar consistency will be seen in other settings, however, these data suggest that in some settings coverage surveys might be conducted as much as one year following an MDA without compromising results. This might enable integration of post-MDA coverage measurement into large, multipurpose, periodic surveys, thereby conserving resources. |
Predictors of health worker performance after Integrated Management of Childhood Illness training in Benin: a cohort study
Steinhardt LC , Onikpo F , Kouame J , Piercefield E , Lama M , Deming MS , Rowe AK . BMC Health Serv Res 2015 15 276 BACKGROUND: Correct treatment of potentially life-threatening illnesses (PLTIs) in children under 5 years, such as malaria, pneumonia, and diarrhea, can substantially reduce mortality. The Integrated Management of Childhood Illness (IMCI) strategy has been shown to improve treatment of child illnesses, but multiple studies have shown that gaps in health worker performance remain after training. To better understand factors related to health worker performance, we analyzed 9,330 patient consultations in Benin from 2001-2002, after training one of the first cohorts of 32 health workers in IMCI. METHODS: With data abstracted from patient registers specially designed for IMCI-trained health workers, we examined associations between health facility-, health worker-, and patient-level factors and 10 case-management outcomes for PLTIs. RESULTS: Altogether, 63.6 % of children received treatment for all their PLTIs in accordance with IMCI guidelines, and 77.8 % received life-saving treatment (i.e., clinically effective treatment, even if not exactly in accordance with IMCI guidelines). Performance of individual health workers varied greatly, from 15-88 % of patients treated correctly, on average. Multivariate regression analyses identified several factors that might have influenced case-management quality, many outside a manager's direct control. Younger health workers significantly outperformed older ones, and infants received better care than older children. Children with danger signs, those with more complex illnesses, and those with anemia received worse care. Health worker supervision was associated with improved performance for some outcomes. CONCLUSIONS: A variety of factors, some outside the direct control of program managers, can influence health worker practices. An understanding of these influences can help inform the development of strategies to improve performance. |
Unprogrammed deworming in the Kibera slum, Nairobi: implications for control of soil-transmitted helminthiases
Harris JR , Worrell CM , Davis SM , Odero K , Mogeni OD , Deming MS , Mohammed A , Montgomery JM , Njenga SM , Fox LM , Addiss DG . PLoS Negl Trop Dis 2015 9 (3) e0003590 BACKGROUND: Programs for control of soil-transmitted helminth (STH) infections are increasingly evaluating national mass drug administration (MDA) interventions. However, "unprogrammed deworming" (receipt of deworming drugs outside of nationally-run STH control programs) occurs frequently. Failure to account for these activities may compromise evaluations of MDA effectiveness. METHODS: We used a cross-sectional study design to evaluate STH infection and unprogrammed deworming among infants (aged 6-11 months), preschool-aged children (PSAC, aged 1-4 years), and school-aged children (SAC, aged 5-14 years) in Kibera, Kenya, an informal settlement not currently receiving nationally-run MDA for STH. STH infection was assessed by triplicate Kato-Katz. We asked heads of households with randomly-selected children about past-year receipt and source(s) of deworming drugs. Local non-governmental organizations (NGOs) and school staff participating in school-based deworming were interviewed to collect information on drug coverage. RESULTS: Of 679 children (18 infants, 184 PSAC, and 477 SAC) evaluated, 377 (55%) reported receiving at least one unprogrammed deworming treatment during the past year. PSAC primarily received treatments from chemists (48.3%) or healthcare centers (37.7%); SAC most commonly received treatments at school (55.0%). Four NGOs reported past-year deworming activities at 47 of >150 schools attended by children in our study area. Past-year deworming was negatively associated with any-STH infection (34.8% vs 45.4%, p = 0.005). SAC whose most recent deworming medication was sourced from a chemist were more often infected with Trichuris (38.0%) than those who received their most recent treatment from a health center (17.3%) or school (23.1%) (p = 0.05). CONCLUSION: Unprogrammed deworming was received by more than half of children in our study area, from multiple sources. Both individual-level treatment and unprogrammed preventive chemotherapy may serve an important public health function, particularly in the absence of programmed deworming; however, they may also lead to an overestimation of programmed MDA effectiveness. A standardized, validated tool is needed to assess unprogrammed deworming. |
An LC-MS/MS method for serum methylmalonic acid suitable for monitoring vitamin B12 status in population surveys
Mineva EM , Zhang M , Rabinowitz DJ , Phinney KW , Pfeiffer CM . Anal Bioanal Chem 2014 407 (11) 2955-64 Methylmalonic acid (MMA), a functional indicator of vitamin B12 insufficiency, was measured in the US population in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004 using a GC/MS procedure that required 275 muL of sample and had a low throughput (36 samples/run). Our objective was to introduce a more efficient yet highly accurate LC-MS/MS method for NHANES 2011-2014. We adapted the sample preparation with some modifications from a published isotope-dilution LC-MS/MS procedure. The procedure utilized liquid-liquid extraction and generation of MMA dibutyl ester. Reversed-phase chromatography with isocratic elution allowed baseline resolution of MMA from its naturally occurring structural isomer succinic acid within 4.5 min. Our new method afforded an increased throughput (≤160 samples/run) and measured serum MMA with high sensitivity (LOD = 22.1 nmol/L) in only 75 muL of sample. Mean (+/-SD) recovery of MMA spiked into serum (2 d, 4 levels, 2 replicates each) was 94 % +/- 5.5 %. Total imprecision (41 d, 2 replicates each) for three serum quality control pools was 4.9 %-7.9 % (97.1-548 nmol/L). The LC-MS/MS method showed excellent correlation (n = 326, r = 0.99) and no bias (Deming regression, Bland-Altman analysis) compared to the previous GC/MS method. Both methods produced virtually identical mean (+/-SD) MMA concentrations [LC-MS/MS: 18.47 +/- 0.71 ng/mL (n = 17), GC/MS: 18.18 +/- 0.67 ng/mL (n = 11)] on a future plasma reference material compared with a GC/MS method procedure from the National Institute of Standards and Technology [18.41 +/- 0.70 ng/mL (n = 15)]. No adjustment will be necessary to compare previous (1999-2004) to future (2011-2014) NHANES MMA data. |
Impact of a community-based lymphedema management program on episodes of adenolymphangitis (ADLA) and lymphedema progression - Odisha State, India
Mues KE , Deming M , Kleinbaum DG , Budge PJ , Klein M , Leon JS , Prakash A , Rout J , Fox LM . PLoS Negl Trop Dis 2014 8 (9) e3140 BACKGROUND: Lymphedema management programs have been shown to decrease episodes of adenolymphangitis (ADLA), but the impact on lymphedema progression and of program compliance have not been thoroughly explored. Our objectives were to determine the rate of ADLA episodes and lymphedema progression over time for patients enrolled in a community-based lymphedema management program. We explored the association between program compliance and ADLA episodes as well as lymphedema progression. METHODOLOGY/PRINCIPAL FINDINGS: A lymphedema management program was implemented in Odisha State, India from 2007-2010 by the non-governmental organization, Church's Auxiliary for Social Action, in consultation with the Centers for Disease Control and Prevention. A cohort of patients was followed over 24 months. The crude 30-day rate of ADLA episodes decreased from 0.35 episodes per person-month at baseline to 0.23 at 24 months. Over the study period, the percentage of patients who progressed to more severe lymphedema decreased (P-value = 0.0004), while those whose lymphedema regressed increased over time (P-value<0.0001). Overall compliance to lymphedema management, lagged one time point, appeared to have little to no association with the frequency of ADLA episodes among those without entry lesions (RR = 0.87 (0.69, 1.10)) and was associated with an increased rate (RR = 1.44 (1.11, 1.86)) among those with entry lesions. Lagging compliance two time points, it was associated with a decrease in the rate of ADLA episodes among those with entry lesions (RR = 0.77 (95% CI: 0.59, 0.99)) and was somewhat associated among those without entry lesions (RR = 0.83 (95% CI: 0.64, 1.06)). Compliance to soap was associated with a decreased rate of ADLA episodes among those without inter-digital entry lesions. CONCLUSIONS/SIGNIFICANCE: These results indicate that a community-based lymphedema management program is beneficial for lymphedema patients for both ADLA episodes and lymphedema. It is one of the first studies to demonstrate an association between program compliance and rate of ADLA episodes. |
Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration: a multicenter evaluation
Chu BK , Deming M , Biritwum NK , Bougma WR , Dorkenoo AM , El-Setouhy M , Fischer PU , Gass K , Gonzalez de Pena M , Mercado-Hernandez L , Kyelem D , Lammie PJ , Flueckiger RM , Mwingira UJ , Noordin R , Offei Owusu I , Ottesen EA , Pavluck A , Pilotte N , Rao RU , Samarasekera D , Schmaedick MA , Settinayake S , Simonsen PE , Supali T , Taleo F , Torres M , Weil GJ , Won KY . PLoS Negl Trop Dis 2013 7 (12) e2584 BACKGROUND: Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. METHODOLOGY: The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6-7 year olds or 1(st)-2(nd) graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs. PRINCIPAL FINDINGS/CONCLUSIONS: In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance requires further investigation. |
Institutionalizing public health department accreditation through CDC opportunities
Monroe J , Collins J , Ikeda R , Khabbaz R . J Public Health Manag Pract 2014 20 (1) 141-4 This commentary discusses institutionalizing public health department accreditation through CDC opportunities. To realize these opportunities, it requires the engagement of national, state, and local partners. | Everybody doing his best is not the answer. It is first necessary that people know what to do. | W. Edwards Deming | The Centers for Disease Control and Prevention (CDC) mission is to help create the expertise, information, and tools that people and communities need to protect their health—through health promotion; prevention of disease, injury, and disability; and preparedness to promptly address new health threats. It has a long-standing partnership with state, tribal, local, and territorial health departments to help accomplish and further the public health mission. States and localities have the legal responsibility for public health and serve on the front lines as the first to recognize and respond to health threats. The federal government, on the contrary, has resources, expertise, and the responsibility to assess the health of the nation and make recommendations for improvement.1 Given the diversity in size, structure, and activities in health departments, developing standards for governmental public health practice has been a long-standing challenge. Fortunately, the collaborative work necessary to establish accreditation through the Public Health Accreditation Board (PHAB) has forged a national consensus on standards for public health departments. |
Exserohilum infections associated with contaminated steroid injections: a clinicopathologic review of 40 cases
Ritter JM , Muehlenbachs A , Blau DM , Paddock CD , Shieh WJ , Drew CP , Batten BC , Bartlett JH , Metcalfe MG , Pham CD , Lockhart SR , Patel M , Liu L , Jones TL , Greer PW , Montague JL , White E , Rollin DC , Seales C , Stewart D , Deming MV , Brandt ME , Zaki SR . Am J Pathol 2013 183 (3) 881-92 September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intra-articular injections. Contamination of methylprednisolone acetate with the black mold, Exserohilum rostratum, was the primary cause of the outbreak, with >13,000 persons exposed to the potentially contaminated drug, 741 confirmed drug-related infections, and 55 deaths. Fatal meningitis and localized epidural, paraspinal, and peripheral joint infections occurred. Tissues from 40 laboratory-confirmed cases representing these various clinical entities were evaluated by histopathological analysis, special stains, and IHC to characterize the pathological features and investigate the pathogenesis of infection, and to evaluate methods for detection of Exserohilum in formalin-fixed, paraffin-embedded (FFPE) tissues. Fatal cases had necrosuppurative to granulomatous meningitis and vasculitis, with thrombi and abundant angioinvasive fungi, with extensive involvement of the basilar arterial circulation of the brain. IHC was a highly sensitive method for detection of fungus in FFPE tissues, demonstrating both hyphal forms and granular fungal antigens, and PCR identified Exserohilum in FFPE and fresh tissues. Our findings suggest a pathogenesis for meningitis involving fungal penetration into the cerebrospinal fluid at the injection site, with transport through cerebrospinal fluid to the basal cisterns and subsequent invasion of the basilar arteries. Further studies are needed to characterize Exserohilum and investigate the potential effects of underlying host factors and steroid administration on the pathogenesis of infection. |
Isotope-dilution liquid chromatography/tandem mass spectrometry candidate reference method for total testosterone in human serum
Botelho JC , Shacklady C , Cooper HC , Tai SS , Van Uytfanghe K , Thienpont LM , Vesper HW . Clin Chem 2012 59 (2) 372-80 BACKGROUND: We developed and evaluated a candidate reference measurement procedure (RMP) to standardize testosterone measurements, provide highly accurate and precise value assignments for the CDC Hormone Standardization Program, and ensure accurate and comparable results across testing systems and laboratories. METHODS: After 2 liquid/liquid extractions of serum with a combination of ethyl acetate and hexane, we quantified testosterone by isotope-dilution liquid chromatography/tandem mass spectrometry with electrospray ionization in the positive ion mode monitoring 289-->97 m/z (testosterone) and 292-->112 m/z ((3)C(13) testosterone). We used calibrator bracketing and gravimetric measurements to give higher specificity and accuracy to serum value assignments. The candidate RMP was evaluated for accuracy by use of NIST-certified reference material SRM971 and validated by split-sample comparison to established RMPs. We evaluated intraassay and interassay imprecision, measurement uncertainty, potential interferences, and matrix effects. RESULTS: A weighted Deming regression comparison of the candidate RMP to established RMPs showed agreement with no statistical difference (slope 0.99, 95% CI 0.98-1.00, intercept 0.54, 95% CI -1.24 to 2.32) and a bias of ≤0.3% for NIST SRM971. The candidate RMP gave maximum intraassay, interassay, and total percent CVs of 1.5%, 1.4%, and 1.7% across the concentrations of testosterone typically found in healthy men and women. We tested structural analogs of testosterone and 125 serum samples and found no interferences with the measurement. CONCLUSIONS: This RMP for testosterone can serve as a higher-order standard for measurement traceability and can be used to provide an accuracy base to which routine methods can be compared in the CDC Hormone Standardization Program. |
Trends in health worker performance after implementing the Integrated Management of Childhood Illness strategy in Benin
Rowe AK , Osterholt DM , Kouame J , Piercefield E , Herman KM , Onikpo F , Lama M , Deming MS . Trop Med Int Health 2012 17 (4) 438-446 OBJECTIVE: Training health workers to use Integrated Management of Childhood Illness (IMCI) guidelines can improve care for ill children in outpatient settings in developing countries. However, even after IMCI training, important performance gaps exist. One potential reason is that the effect of training can rapidly wane. Our aim was to determine if the performance of IMCI-trained health workers deteriorated over 3 years. METHODS: We studied two departments in Benin. First, we performed a record review of 32 IMCI-trained health workers during the first year of IMCI implementation (2001-2002). Second, we analysed data from cross-sectional health facility surveys from 2001 to 2004 that represented the entire study area. Primary outcomes were the proportion of children under 5 years old with potentially life-threatening illnesses who received either recommended or adequate treatment, and among all children, an index of overall guideline adherence. Secondary outcomes reflected the treatment of individual diseases. Outcomes were calculated monthly, and time trends were evaluated with regression modelling. RESULTS: The record review included 9393 consultations, and the surveys included 411 consultations performed by 105 health workers. For both data sources, performance trends were essentially flat for nearly all outcomes. Absolute levels of performance revealed substantial performance gaps. CONCLUSIONS: We found no evidence that performance declined over 3 years after IMCI training. However, important performance gaps found immediately after IMCI training persisted and should be addressed. (2012 Blackwell Publishing Ltd.) |
Pandemic (H1N1) 2009 and Hajj pilgrims who received predeparture vaccination, Egypt
Kandeel A , Deming M , Kereem EA , El-Refay S , Afifi S , Abukela M , Earhart K , El-Sayed N , El-Gabaly H . Emerg Infect Dis 2011 17 (7) 1266-1268 In Egypt, vaccination against pandemic (H1N1) 2009 virus was required of pilgrims departing for the 2009 Hajj. A survey of 551 pilgrims as they returned to Egypt found 542 (98.1% [weighted]) reported receiving the vaccine; 6 (1.0% [weighted]) were infected with influenza virus A (H3N2) but none with pandemic (H1N1) 2009 virus. |
Impact of a malaria-control project in Benin that included the Integrated Management of Childhood Illness strategy
Rowe A , Onikpo F , Lama M , Osterholt D , Deming M . Am J Public Health 2011 101 (12) 2333-41 OBJECTIVES: To estimate the impact of the Integrated Management of Childhood Illness (IMCI) strategy on early-childhood mortality, we evaluated a malaria-control project in Benin that implemented IMCI and promoted insecticide-treated nets (ITNs). METHODS: We conducted a before-and-after intervention study that included a nonrandomized comparison group. We used the preceding birth technique to measure early-childhood mortality (risk of dying before age 30 months), and we used health facility surveys and household surveys to measure process indicators. RESULTS: Most process indicators improved in the area covered by the intervention. Notably, because ITNs were also promoted in the comparison area children's ITN use increased by about 20 percentage points in both areas. Regarding early-childhood mortality, the trend from baseline (1999-2001) to follow-up (2002-2004) for the intervention area (13.0% decrease; P<.001) was 14.1% (P<.001) lower than was the trend for the comparison area (1.3% increase; P=.46). CONCLUSIONS: Mortality decreased in the intervention area after IMCI and ITN promotion. ITN use increased similarly in both study areas, so the mortality impact of ITNs in the 2 areas might have canceled each other out. Thus, the mortality reduction could have been primarily attributable to IMCI's effect on health care quality and care-seeking. (Am J Public Health. Published online ahead of print May 12, 2011: e1-e9. doi:10.2105/AJPH.2010.300068). |
Mapping, monitoring, and surveillance of neglected tropical diseases: towards a policy framework
Baker MC , Mathieu E , Fleming FM , Deming M , King JD , Garba A , Koroma JB , Bockarie M , Kabore A , Sankara DP , Molyneux DH . Lancet 2010 375 (9710) 231-8 As national programmes respond to the new opportunities presented for scaling up preventive chemotherapy programmes for the coadministration of drugs to target lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma, possible synergies between existing disease-specific policies and protocols need to be examined. In this report we compare present policies for mapping, monitoring, and surveillance for these diseases, drawing attention to both the challenges and opportunities for integration. Although full integration of all elements of mapping, monitoring, and surveillance strategies might not be feasible for the diseases targeted through the preventive chemotherapy approach, there are opportunities for integration, and we present examples of integrated strategies. Finally, if advantage is to be taken of scaled up interventions to address neglected tropical diseases, efforts to develop rapid, inexpensive, and easy-to-use methods, whether disease-specific or integrated, should be increased. We present a framework for development of an integrated monitoring and evaluation system that combines both integrated and disease-specific strategies. |
The rise and fall of supervision in a project designed to strengthen supervision of Integrated Management of Childhood Illness in Benin
Rowe AK , Onikpo F , Lama M , Deming MS . Health Policy Plan 2009 25 (2) 125-34 OBJECTIVE: In developing countries, supervision is a widely recognized strategy for improving health worker performance; and anecdotally, maintaining regular, high-quality supervision is difficult. However, remarkably little research has explored in depth why supervision is so challenging. METHODS: In the context of a trial to improve health worker adherence to Integrated Management of Childhood Illness (IMCI) guidelines and strengthen supervision in southeastern Benin, we used record reviews, focus group discussions, key informant interviews, and cross-sectional surveys to examine the supervision process. FINDINGS: Initially, little IMCI supervision occurred. The frequency increased substantially after implementing a series of workshops, but then deteriorated. Quantitative and qualitative data revealed obstacles to supervision at multiple levels of the health system. Based on supervisors' opinions, the main problems were: poor coordination; inadequate management skills and ineffective management teams; a lack of motivation; problems related to decentralization; health workers sometimes resisting IMCI implementation; and less priority given to IMCI supervision because of incentives for non-supervision activities, a lack of leadership, and an expectation of integrated supervision. To this list, based on our observations, we add: the increasing supervision workload, time required for non-supervision activities, project interventions not always being implemented as planned, and the loss of particularly effective supervisors. In terms of correctly completing steps of the supervision process, the quality of supervision was generally good. CONCLUSIONS: Managers should monitor supervision, understand the evolving influences on supervision, and use their resources and authority to both promote supervision and remove impediments to supervision. Support from leaders can be crucial, thus donors and politicians should help make supervision a true priority. As with front-line clinicians, supervisors are health workers who need support. We emphasize the importance of research to identify effective and affordable strategies for improving supervision frequency and quality. (ClinicalTrials.gov number NCT00510679.). |
Comparison of national malaria surveillance system with the national notifiable diseases surveillance system in the United States
Hwang J , McClintock S , Kachur SP , Slutsker L , Arguin P . J Public Health Manag Pract 2009 15 (4) 345-51 BACKGROUND: The Centers for Disease Control and Prevention (CDC) is in the process of integrating the existing dual mechanisms for reporting cases of malaria diagnosed in the United States into a single electronic reporting mechanism. Before adoption of this new system, an evaluation of the existing systems for state-level reporting of malaria data to the CDC was conducted. METHODS: CDC guidelines for evaluating surveillance systems were used to assess the attributes of the National Malaria Surveillance System (NMSS), the current National Notifiable Diseases Surveillance System (NNDSS), and the projected fully integrated NNDSS. We analyzed data collected from NMSS and NNDSS from 2001 to 2005 using the Chandra-Sekar-Deming method to estimate completeness of reporting. RESULTS: The projected fully integrated system was assessed likely to perform better than either of the existing systems on all attributes except stability. The overall completeness of reporting was estimated to be 80.3 percent for NNDSS and 74.7 percent for NMSS. CONCLUSIONS: Both existing systems have reasonably high ascertainment of cases. A fully integrated system with malaria-specific data fields would improve upon existing systems if it proved to be stable. |
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