Last data update: May 20, 2024. (Total: 46824 publications since 2009)
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Query Trace: Battle N [original query] |
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Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021
Rogier E , Battle N , Bakari C , Seth MD , Nace D , Herman C , Barakoti A , Madebe RA , Mandara CI , Lyimo BM , Giesbrecht DJ , Popkin-Hall ZR , Francis F , Mbwambo D , Garimo I , Aaron S , Lusasi A , Molteni F , Njau R , Cunningham JA , Lazaro S , Mohamed A , Juliano JJ , Bailey JA , Udhayakumar V , Ishengoma DS . Sci Rep 2024 14 (1) 8158 Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes ≥ 5% of RDTs to return false negative results. Tanzania is a country of heterogenous P. falciparum transmission, with some regions approaching elimination and others at varying levels of control. In concordance with the current recommended WHO pfhrp2 deletion surveillance strategy, 100 health facilities encompassing 10 regions of Tanzania enrolled malaria-suspected patients between February and July 2021. Of 7863 persons of all ages enrolled and providing RDT result and blood sample, 3777 (48.0%) were positive by the national RDT testing for Plasmodium lactate dehydrogenase (pLDH) and/or HRP2. A second RDT testing specifically for the P. falciparum LDH (Pf-pLDH) antigen found 95 persons (2.5% of all RDT positives) were positive, though negative by the national RDT for HRP2, and were selected for pfhrp2 and pfhrp3 (pfhrp2/3) genotyping. Multiplex antigen detection by laboratory bead assay found 135/7847 (1.7%) of all blood samples positive for Plasmodium antigens but very low or no HRP2, and these were selected for genotyping as well. Of the samples selected for genotyping based on RDT or laboratory multiplex result, 158 were P. falciparum DNA positive, and 140 had sufficient DNA to be genotyped for pfhrp2/3. Most of these (125/140) were found to be pfhrp2+/pfhrp3+, with smaller numbers deleted for only pfhrp2 (n = 9) or only pfhrp3 (n = 6). No dual pfhrp2/3 deleted parasites were observed. This survey found that parasites with these gene deletions are rare in Tanzania, and estimated that 0.24% (95% confidence interval: 0.08% to 0.39%) of false-negative HRP2-RDTs for symptomatic persons were due to pfhrp2 deletions in this 2021 Tanzania survey. These data provide evidence for HRP2-based diagnostics as currently accurate for P. falciparum diagnosis in Tanzania. |
Evaluating the performance of Plasmodium falciparum genetic metrics for inferring National Malaria Control Programme reported incidence in Senegal
Wong W , Schaffner SF , Thwing J , Seck MC , Gomis J , Diedhiou Y , Sy N , Ndiop M , Ba F , Diallo I , Sene D , Diallo MA , Ndiaye YD , Sy M , Sene A , Sow D , Dieye B , Tine A , Ribado J , Suresh J , Lee A , Battle KE , Proctor JL , Bever CA , MacInnis B , Ndiaye D , Hartl DL , Wirth DF , Volkman SK . Malar J 2024 23 (1) 68 BACKGROUND: Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. METHODS: This study examined parasites from 3147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. RESULTS: Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (< 10/1000/annual [‰]). CONCLUSIONS: When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence > 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was < 10‰, many of the correlations between parasite genetics and incidence were reversed, which may reflect the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low. |
Evaluating the performance of Plasmodium falciparum genetics for inferring National Malaria Control Program reported incidence in Senegal
Wong W , Schaffner SF , Thwing J , Seck MC , Gomis J , Diedhiou Y , Sy N , Ndiop M , Ba F , Diallo I , Sene D , Diallo MA , Ndiaye YD , Sy M , Sene A , Sow D , Dieye B , Tine A , Ribado J , Suresh J , Lee A , Battle KE , Proctor JL , Bever CA , MacInnis B , Ndiaye D , Hartl DL , Wirth DF , Volkman SK . Res Sq 2023 Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programs (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. Here, we examined parasites from 3,147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, we constructed a series of Poisson generalized linear mixed-effects models to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. We compared the model-predicted incidence with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (<10/1000/annual [‰]). When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence >10 ‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was <10 ‰, we found that many of the correlations between parasite genetics and incidence were reversed, which we hypothesize reflects the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low. |
Force health surveillance in the NATO does not meet the needs of its users: A structured evaluation of EpiNATO-2
Rowh A , Lindfield R , Gaines J . Mil Med 2023 INTRODUCTION: Disease and non-battle injuries (DNBIs) cause substantial losses among military personnel. NATO has monitored DNBIs among its personnel since 1996 using multiple versions of a tool now called EpiNATO-2, but the surveillance system has never been systematically evaluated. Following a request from NATO to the CDC, the objective of this study was to assess surveillance system attributes of EpiNATO-2 using CDC's updated guidelines for evaluating public health surveillance systems. MATERIALS AND METHODS: Between June and October 2022, a literature review and key informant interviews were conducted to assess the following attributes: usefulness, simplicity, flexibility, data quality, acceptability, sensitivity, positive predictive value, representativeness, timeliness, stability, informatics system quality, informatics service quality, and informatics interoperability. Key informant interviews were conducted in Kosovo, Germany, and remotely with EpiNATO-2 users spanning three levels: clinical and data entry personnel (tactical level); regional medical and public health officers (operational level); and senior commanders and other governmental entities (strategic level). RESULTS: Fourteen EpiNATO-2 users participated in interviews, representing 3 of the 5 major NATO missions, 3 partner entities, and 7 nationalities. All users (100%) reported that the system did not meet their needs, with most users noting the following challenges: lack of clearly defined system objectives; poor data quality due to ambiguous case definitions and frequently unsubmitted reports (37% missing during January to June 2022); long delay between the occurrence of health events and the availability of corresponding data (≥2 weeks); and an antiquated and inflexible data management system. Overall, performance was deemed unsatisfactory on 11 of the 13 attributes. CONCLUSIONS: This multinational sample of EpiNATO-2 users at all military levels reported that the system is currently not useful with respect to its stated objectives. Opportunities exist to improve the performance and usefulness of EpiNATO-2: improve case definitions, modernize data infrastructure, and regularly evaluate the surveillance system. |
Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal
Schaffner SF , Badiane A , Khorgade A , Ndiop M , Gomis J , Wong W , Ndiaye YD , Diedhiou Y , Thwing J , Seck MC , Early A , Sy M , Deme A , Diallo MA , Sy N , Sene A , Ndiaye T , Sow D , Dieye B , Ndiaye IM , Gaye A , Ndiaye A , Battle KE , Proctor JL , Bever C , Fall FB , Diallo I , Gaye S , Sene D , Hartl DL , Wirth DF , MacInnis B , Ndiaye D , Volkman SK . Nat Commun 2023 14 (1) 7268 We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study's goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure. |
Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal (preprint)
Schaffner SF , Badiane A , Khorgade A , Ndiop M , Gomis J , Wong W , Ndiaye YD , Diedhiou Y , Thwing J , Seck MC , Early A , Sy M , Deme A , Diallo MA , Sy N , Sene A , Ndiaye T , Sow D , Dieye B , Ndiaye IM , Gaye A , Ndiaye A , Battle KE , Proctor JL , Bever C , Fall FB , Diallo I , Gaye S , Sene D , Hartl DL , Wirth DF , MacInnis B , Ndiaye D , Volkman SK . medRxiv 2023 17 Parasite genetic surveillance has the potential to play an important role in malaria control. We describe here an analysis of data from the first year of an ongoing, nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal, intended to provide actionable information for malaria control efforts. Looking for a good proxy for local malaria incidence, we found that the best predictor was the proportion of polygenomic infections (those with multiple genetically distinct parasites), although that relationship broke down at very low incidence. The proportion of closely related parasites in a site was more weakly correlated with incidence while the local genetic diversity was uninformative. Study of related parasites indicated their potential for discriminating local transmission patterns: two nearby study areas had similarly high fractions of relatives, but one area was dominated by clones and the other by outcrossed relatives. Throughout the country, most related parasites proved to belong to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci as well as at one novel locus, reflective of ongoing selection pressure. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Acceptability, feasibility, drug safety, and effectiveness of a pilot mass drug administration with a single round of sulfadoxine-pyrimethamine plus primaquine and indoor residual spraying in communities with malaria transmission in Haiti, 2018
Chang MA , Impoinvil D , Hamre KES , Dalexis PE , Mérilien JB , Dismer AM , Fouché B , Desir L , Holmes K , Lafortune W , Herman C , Rogier E , Noland GS , Young AJ , Druetz T , Ashton R , Eisele TP , Cohen J , van den Hoogen L , Stresman G , Drakeley C , Pothin E , Cameron E , Battle KE , Williamson J , Telfort MA , Lemoine JF . Am J Trop Med Hyg 2023 108 (6) 1127-1139 For a malaria elimination strategy, Haiti's National Malaria Control Program piloted a mass drug administration (MDA) with indoor residual spraying (IRS) in 12 high-transmission areas across five communes after implementing community case management and strengthened surveillance. The MDA distributed sulfadoxine-pyrimethamine and single low-dose primaquine to eligible residents during house visits. The IRS campaign applied pirimiphos-methyl insecticide on walls of eligible houses. Pre- and post-campaign cross-sectional surveys were conducted to assess acceptability, feasibility, drug safety, and effectiveness of the combined interventions. Stated acceptability for MDA before the campaign was 99.2%; MDA coverage estimated at 10 weeks post-campaign was 89.6%. Similarly, stated acceptability of IRS at baseline was 99.9%; however, household IRS coverage was 48.9% because of the high number of ineligible houses. Effectiveness measured by Plasmodium falciparum prevalence at baseline and 10 weeks post-campaign were similar: 1.31% versus 1.43%, respectively. Prevalence of serological markers were similar at 10 weeks post-campaign compared with baseline, and increased at 6 months. No severe adverse events associated with the MDA were identified in the pilot; there were severe adverse events in a separate, subsequent campaign. Both MDA and IRS are acceptable and feasible interventions in Haiti. Although a significant impact of a single round of MDA/IRS on malaria transmission was not found using a standard pre- and post-intervention comparison, it is possible there was blunting of the peak transmission. Seasonal malaria transmission patterns, suboptimal IRS coverage, and low baseline parasitemia may have limited the effectiveness or the ability to measure effectiveness. |
Notes from the field: Prevalence of previous dengue virus infection among children and adolescents - U.S. Virgin Islands, 2022
Mac VV , Wong JM , Volkman HR , Perez-Padilla J , Wakeman B , Delorey M , Biggerstaff BJ , Fagre A , Gumbs A , Drummond A , Zimmerman B , Lettsome B , Medina FA , Paz-Bailey G , Lawrence M , Ellis B , Rosenblum HG , Carroll J , Roth J , Rossington J , Meeker JR , Joseph J , Janssen J , Ekpo LL , Carrillo M , Hernandez N , Charles P , Tosado R , Soto R , Battle S , Bart SM , Wanga V , Valentin W , Powell W , Battiste Z , Ellis EM , Adams LE . MMWR Morb Mortal Wkly Rep 2023 72 (11) 288-289 In May 2019, the Food and Drug Administration issued approval for Dengvaxia (Sanofi Pasteur), a live-attenuated, chimeric tetravalent dengue vaccine (1). In June 2021, the Advisory Committee on Immunization Practices (ACIP) recommended vaccination with Dengvaxia for children and adolescents aged 9–16 years with laboratory confirmation of previous dengue virus infection and who live in areas with endemic dengue transmission, such as the U.S. Virgin Islands (USVI)† (2). Confirming previous dengue virus infection before vaccine administration (prevaccination screening) is important because 1) although Dengvaxia decreases hospitalization and severe disease from dengue among persons with a previous infection, it increases the risk for these outcomes among persons without a previous infection; 2) many dengue virus infections are asymptomatic; and 3) many patients with symptomatic infections do not seek medical attention or receive appropriate testing (3). Sufficient laboratory evidence of previous dengue virus infection includes a history of laboratory-confirmed dengue§ or a positive serologic test result that meets ACIP-recommended performance standards for prevaccination screening, defined as high specificity (≥98%) and sensitivity (≥75%). A seroprevalence of 20% in the vaccine-eligible population (corresponding to a positive predictive value of ≥90% for a test with minimum sensitivity of 75% and minimum specificity of 98%) is recommended to maximize vaccine safety and minimize the risk for vaccinating persons without a previous dengue virus infection (2). |
Past as prologue-use of rubella vaccination program lessons to inform COVID-19 vaccination
Dixon MG , Reef SE , Zimmerman LA , Grant GB . Emerg Infect Dis 2022 28 (13) S225-s231 The rapid rollout of vaccines against COVID-19 as a key mitigation strategy to end the global pandemic might be informed by lessons learned from rubella vaccine implementation in response to the global rubella epidemic of 1963-1965. That rubella epidemic led to the development of a rubella vaccine that has been introduced in all but 21 countries worldwide and has led to elimination of rubella in 93 countries. Although widespread introduction and use of rubella vaccines was slower than that for COVID-19 vaccines, the process can provide valuable insights for the continued battle against COVID-19. Experiences from the rubella disease control program highlight the critical and evolving elements of a vaccination program, including clearly delineated goals and strategies, regular data-driven revisions to the program based on disease and vaccine safety surveillance, and evaluations to identify the vaccine most capable of achieving disease control targets. |
Performance of antigen detection for HRP2-based malaria rapid diagnostic tests in community surveys: Tanzania, July-November 2017
Rogier E , Bakari C , Mandara CI , Chiduo MG , Plucinski M , Nace D , Battle N , Chacky F , Rumisha SF , Molteni F , Mandike R , Mkude S , Njau R , Mohamed A , Udhayakumar V , Ishengoma DS . Malar J 2022 21 (1) 361 BACKGROUND: Malaria rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum histidine-rich protein 2 (HRP2) antigen are widely used for detection of active infection with this parasite and are the only practical malaria diagnostic test in some endemic settings. External validation of RDT results from field surveys can confirm appropriate RDT performance. METHODS: A community-based cross-sectional survey was conducted between July and November 2017 enrolling participants of all ages in households from 15 villages in four border regions of Tanzania: Geita, Kigoma, Mtwara and Ruvuma. All participants had an RDT performed in the field and provided a blood sample for later laboratory multiplex antigen detection of HRP2. In assessing the continuous HRP2 levels in participant blood versus RDT result, dose-response logistic regression provided quantitative estimates for HRP2 limit of detection (LOD). RESULTS: From the 15 study villages, 6941 persons were enrolled that had a RDT at time of enrollment and provided a DBS for later laboratory antigen detection. RDT positive prevalence for the HRP2 band by village ranged from 20.0 to 43.6%, but the magnitude of this prevalence did not have an effect on the estimated LOD of RDTs utilized in different villages. Overall, HRP2 single-target tests had a lower LOD at the 95% probability of positive RDT (4.3 ng/mL; 95% CI 3.4-5.4) when compared to pLDH/HRP2 dual target tests (5.4 ng/mL; 4.5-6.3), though this difference was not significant. With the exception of one village, all other 14 villages (93.3%) showed RDT LOD estimates at 90% probability of positive RDT between 0.5 and 12.0 ng/mL. CONCLUSIONS: Both HRP2-only and pLDH/HRP2 combo RDTs utilized in a 2017 Tanzania cross-sectional survey of border regions generally performed well, and reliably detected HRP2 antigen in the low ng/mL range. Though single target tests had lower levels of HRP2 detection, both tests were within similar ranges among the 15 villages. Comparison of quantitative HRP2 detection limits among study sites can help interpret RDT testing results when generating population prevalence estimates for malaria infection. |
Mapping the endemicity and seasonality of clinical malaria for intervention targeting in Haiti using routine case data
Cameron E , Young AJ , Twohig KA , Pothin E , Bhavnani D , Dismer A , Merilien JB , Hamre K , Meyer P , Le Menach A , Cohen JM , Marseille S , Lemoine JF , Telfort MA , Chang MA , Won K , Knipes A , Rogier E , Amratia P , Weiss DJ , Gething PW , Battle KE . Elife 2021 10 Towards the goal of malaria elimination on Hispaniola, the National Malaria Control Program of Haiti and its international partner organisations are conducting a campaign of interventions targeted to high-risk communities prioritised through evidence-based planning. Here we present a key piece of this planning: an up-to-date, fine-scale endemicity map and seasonality profile for Haiti informed by monthly case counts from 771 health facilities reporting from across the country throughout the 6-year period from January 2014 to December 2019. To this end, a novel hierarchical Bayesian modelling framework was developed in which a latent, pixel-level incidence surface with spatio-temporal innovations is linked to the observed case data via a flexible catchment sub-model designed to account for the absence of data on case household locations. These maps have focussed the delivery of indoor residual spraying and focal mass drug administration in the Grand'Anse Department in South-Western Haiti. |
Antibody responses against Anopheles darlingi immunogenic peptides in plasmodium infected humans
Londono-Renteria B , Montiel J , Calvo E , Tobón-Castaño A , Valdivia HO , Escobedo-Vargas K , Romero L , Bosantes M , Fisher ML , Conway MJ , Vásquez GM , Lenhart AE . Front Cell Infect Microbiol 2020 10 455 Introduction: Malaria is still an important vector-borne disease in the New World tropics. Despite the recent decline in malaria due to Plasmodium falciparum infection in Africa, a rise in Plasmodium infections has been detected in several low malaria transmission areas in Latin America. One of the main obstacles in the battle against malaria is the lack of innovative tools to assess malaria transmission risk, and the behavioral plasticity of one of the main malaria vectors in Latin America, Anopheles darlingi. Methods: We used human IgG antibodies against mosquito salivary gland proteins as a measure of disease risk. Whole salivary gland antigen (SGA) from Anopheles darlingi mosquitoes was used as antigen in Western blot experiments, in which a ~65 kDa protein was visualized as the main immunogenic band and sent for sequencing by mass spectrometry. Apyrase and peroxidase peptides were designed and used as antigens in an ELISA-based test to measure human IgG antibody responses in people with different clinical presentations of malaria. Results: Liquid chromatography–mass spectrometry revealed 17 proteins contained in the ~65 kDa band, with an apyrase and a peroxidase as the two most abundant proteins. Detection of IgG antibodies against salivary antigens by ELISA revealed a significant higher antibody levels in people with malaria infection when compared to uninfected volunteers using the AnDar_Apy1 and AnDar_Apy2 peptides. We also detected a significant positive correlation between the anti-peptides IgG levels and antibodies against the Plasmodium vivax and P. falciparum antigens PvMSP1 and PfMSP1. Odd ratios suggest that people with higher IgG antibodies against the apyrase peptides were up to five times more likely to have a malaria infection. Conclusion: Antibodies against salivary peptides from An. darlingi salivary gland proteins may be used as biomarkers for malaria risk. |
Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data
Stresman G , Sepulveda N , Fornace K , Grignard L , Mwesigwa J , Achan J , Miller J , Bridges DJ , Eisele TP , Mosha J , Lorenzo PJ , Macalinao ML , Espino FE , Tadesse F , Stevenson JC , Quispe AM , Siqueira A , Lacerda M , Yeung S , Sovannaroth S , Pothin E , Gallay J , Hamre KE , Young A , Lemoine JF , Chang MA , Phommasone K , Mayxay M , Landier J , Parker DM , Von Seidlein L , Nosten F , Delmas G , Dondorp A , Cameron E , Battle K , Bousema T , Gething P , D'Alessandro U , Drakeley C . Lancet Infect Dis 2020 20 (8) 953-963 BACKGROUND: Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings. METHODS: The proportion of infections detected in routine malaria data, P(Detect), was derived from paired household cross-sectional survey and routinely collected malaria data within health facilities. P(Detect) was estimated using a Bayesian model in 431 clusters spanning the Americas, Africa, and Asia. The association between P(Detect) and malaria prevalence was assessed using log-linear regression models. Changes in P(Detect) over time were evaluated using data from 13 timepoints over 2 years from The Gambia. FINDINGS: The median estimated P(Detect) across all clusters was 12.5% (IQR 5.3-25.0) for P falciparum and 10.1% (5.0-18.3) for P vivax and decreased as the estimated log-PCR community prevalence increased (adjusted odds ratio [OR] for P falciparum 0.63, 95% CI 0.57-0.69; adjusted OR for P vivax 0.52, 0.47-0.57). Factors associated with increasing P(Detect) included smaller catchment population size, high transmission season, improved care-seeking behaviour by infected individuals, and recent increases (within the previous year) in transmission intensity. INTERPRETATION: The proportion of all infections detected within health systems increases once transmission intensity is sufficiently low. The likely explanation for P falciparum is that reduced exposure to infection leads to lower levels of protective immunity in the population, increasing the likelihood that infected individuals will become symptomatic and seek care. These factors might also be true for P vivax but a better understanding of the transmission biology is needed to attribute likely reasons for the observed trend. In low transmission and pre-elimination settings, enhancing access to care and improvements in care-seeking behaviour of infected individuals will lead to an increased proportion of infections detected in the community and might contribute to accelerating the interruption of transmission. FUNDING: Wellcome Trust. |
Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group
Thriemer K , Bobogare A , Ley B , Gudo CS , Alam MS , Anstey NM , Ashley E , Baird JK , Gryseels C , Jambert E , Lacerda M , Laihad F , Marfurt J , Pasaribu AP , Poespoprodjo JR , Sutanto I , Taylor WR , van den Boogaard C , Battle KE , Dysoley L , Ghimire P , Hawley B , Hwang J , Khan WA , Mudin RNB , Sumiwi ME , Ahmed R , Aktaruzzaman MM , Awasthi KR , Bardaji A , Bell D , Boaz L , Burdam FH , Chandramohan D , Cheng Q , Chindawongsa K , Culpepper J , Das S , Deray R , Desai M , Domingo G , Duoquan W , Duparc S , Floranita R , Gerth-Guyette E , Howes RE , Hugo C , Jagoe G , Sariwati E , Jhora ST , Jinwei W , Karunajeewa H , Kenangalem E , Lal BK , Landuwulang C , Le Perru E , Lee SE , Makita LS , McCarthy J , Mekuria A , Mishra N , Naket E , Nambanya S , Nausien J , Duc TN , Thi TN , Noviyanti R , Pfeffer D , Qi G , Rahmalia A , Rogerson S , Samad I , Sattabongkot J , Satyagraha A , Shanks D , Sharma SN , Sibley CH , Sungkar A , Syafruddin D , Talukdar A , Tarning J , Kuile FT , Thapa S , Theodora M , Huy TT , Waramin E , Waramori G , Woyessa A , Wongsrichanalai C , Xa NX , Yeom JS , Hermawan L , Devine A , Nowak S , Jaya I , Supargiyono S , Grietens KP , Price RN . Malar J 2018 17 (1) 241 The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness. |
In Memoriam, Fred Gordin, MD, 1951-2018
Cohn DL , El Sadr WM , Abrams DI , Neaton JD , Benator DA , Vernon AA . Clin Infect Dis 2018 67 (1) 153-153 Dr Fred Gordin passed away on March 18, 2018, after a valiant 4-year battle with adenocarcinoma of the lung. The infectious diseases and pulmonary communities have lost a brilliant researcher, superb clinician, outstanding teacher, and consummate leader. During his career he had a major impact in the fields of mycobacteria, human immunodeficiency virus (HIV), and infection control. |
Getting to zero new tuberculosis infections: Insights from the National Institutes of Health/US Centers for Disease Control and Prevention/Bill & Melinda Gates Foundation Workshop on Research Needs for Halting Tuberculosis Transmission
Shah NS , Kim P , Kana BD , Rustomjee R . J Infect Dis 2017 216 S627-s628 Tuberculosis caused an estimated 1.4 million deaths in 2015 and now ranks as the leading infectious disease cause of mortality in the world [1]. An additional 1.7 billion people are currently infected with Mycobacterium tuberculosis and are at risk of developing active tuberculosis disease. The challenge to eliminate tuberculosis has never been more relevant and urgent. Unfortunately, efforts to bring this global epidemic under control have been hampered by inadequate understanding of the epidemiology, biology, and effective interventions that directly address tuberculosis transmission. Identifying the key drivers of transmission and appending interventions has thus far remained unattainable in many high-burden tuberculosis settings. The large reservoir of subclinical infections, the human immunodeficiency virus (HIV) coepidemic, and a rise in drug resistance make public health efforts to battle this disease complex. For example, in southern Africa, high rates of HIV infection have served as key drivers of the tuberculosis epidemic and have created a complex clinical situation with unique difficulties in diagnosis and tracking infectious individuals; these limitations have seriously hampered tuberculosis elimination in the region [1]. In the United States, intermittent outbreaks of tuberculosis continue to occur despite utilization of modern prevention interventions in a well-funded healthcare system [2]. Globally, the modest declines (of 1.5%) in tuberculosis incidence between 2014 and 2015 fall markedly short of the targeted 4%–5% annual decline that is needed to achieve the 2020 milestones for the global End TB Strategy [3]. Of particular concern, the massive rollouts of new interventions targeted at individual patients, such as molecular diagnostics, preventative therapy, and antiretroviral treatment, and infrastructure investments in renovating healthcare facilities to reduce airborne disease spread have not resulted in sufficient epidemiological impact to meet global goals in reducing tuberculosis incidence [4, 5]. This highlights the need for sharply focused, evidence-led interventions and strategies tailored to individuals and communities, which are complemented by an ambitious implementation science agenda that rapidly translates new research findings to the field. Central to this process should be a paradigm shift toward limiting transmission with improved efficiency and effectiveness and the incorporation of strategies for overcoming the stigma and discrimination that continues to dilute the uptake and utilization of health services. |
Reactions and receptivity to framing HIV prevention message concepts about pre-exposure prophylaxis for black and Latino men who have sex with men in three urban US cities
Mimiaga MJ , Closson EF , Battle S , Herbst JH , Denson D , Pitts N , Holman J , Landers S , Mansergh G . AIDS Patient Care STDS 2016 30 (10) 484-489 Men who have sex with men (MSM) of color are disproportionately affected by HIV in the United States. Pre-exposure prophylaxis (PrEP) using antiretroviral medications is a newer biomedical prevention modality with established efficacy for reducing the risk of acquiring HIV. We conducted formative qualitative research to explore audience reactions and receptivity to message concepts on PrEP as part of the development of prevention messages to promote PrEP awareness among black and Latino MSM in the United States. In 2013, 48 black and 42 Latino (total study sample = 90) mixed HIV serostatus MSM from Chicago, Ft. Lauderdale, and Kansas City participated in either an individual interview or focus group discussion. Men were recruited online and at community-based organizations in each city. We elicited feedback on the comprehensibility, credibility, and relevance of two draft messages on PrEP. The messages included efficacy estimates from iPrEx, a phase III clinical trial to ascertain whether the antiretroviral medication tenofovir/emtricitabine disoproxil fumarate (commercially known as Truvada(R)) could safely and effectively prevent HIV acquisition through sex among MSM and transgender women. With participants' consent, the interviews and focus groups were recorded and transcribed. The data were then summarized and analyzed using a qualitative descriptive approach. The majority of men were unfamiliar with PrEP. It was suggested that additional information about the medication and clinical trials establishing efficacy was needed to enhance the legitimacy and relevancy of the messages. Participants sought to form an opinion of PrEP that was grounded in their own interpretation of the efficacy data. However, confusion about nonadherence among clinical trial subjects and individual versus average risk limited comprehension of these messages. Thematic overlaps suggest that message believability was connected to participants' ability to derive meaning from the PrEP efficacy data. Despite being concerned that other MSM would interpret the messages to mean that condom use was unnecessary while taking PrEP, participants themselves primarily understood PrEP as a supplement rather than a replacement for condoms. Based on their experience with taking antiretroviral medication, HIV-positive men considered condom use a more feasible form of HIV prevention than PrEP. Participants' responses suggest that more information about PrEP and the clinical trial would support the legitimacy of PrEP and the messages as a whole. These details may enhance believability in the concept of PrEP and reinforce confidence in the validity of the efficacy result. |
Equipping Environmental Health Workers With Environmental Assessment Tools
Coleman EW . J Environ Health 2015 78 (1) 36-8 Food-related illnesses affect tens of millions of people and kill thousands in the U.S. each year. They also cause billions of dollars in health care–related and industry costs annually. As a result, the Centers for Disease Control and Prevention (CDC) have identified reducing food-borne diseases as a “winnable battle (CDC, 2013).” To address this issue, in April 2014 CDC’s National Center for Environmental Health launched two food safety tools that are transforming how environmental health workers conduct foodborne illness environmental assessments as part of an outbreak response and how they report these data to prevent future outbreaks. |
Getting everyone to buckle up on every trip: what more can be done?
Baldwin GT , Houry D . Ann Intern Med 2015 163 (3) 234-5 The Centers for Disease Control and Prevention (CDC) focuses on preventing illness, injury, disability, and death. To spotlight attention and focus activity, CDC Director Dr. Thomas Frieden has identified 7 public health “winnable battles.” These battles address public health issues in which judicious action and implementation of evidence-based and scalable interventions would have an immediate positive effect. | The prevention of motor vehicle injuries is a winnable battle, in part, because of the life-saving potential of seat belts and our opportunity to increase their use. The CDC aims to prevent deaths and injuries from motor vehicle crashes by focusing on modifiable behaviors through coordinated, sustained, and complementary actions with the U.S. Department of Transportation, especially the National Highway Traffic Safety Administration. | The most effective intervention to reduce injury of motor vehicle occupants in a crash is simple: Wear a seat belt. Seat belts reduce the risk for fatal injuries by approximately 45% and serious injuries by approximately 50% when worn in a motor vehicle crash (1). Seat belts are a critical and cross-cutting secondary prevention strategy. They protect persons regardless of who is at fault or the root cause of the crash, including those involved in crashes that result from the negligence of alcohol-impaired drivers and from distracted driving. Seat belts have saved the lives of 300 000 Americans since 1975, including more than 12 500 Americans in 2013 alone (1, 2). In that same year, approximately 2800 more Americans would be alive today if all unrestrained passenger vehicle occupants aged 5 years or older involved in a fatal crash had buckled up (2). |
Public health national approach to reducing breast and cervical cancer disparities
Miller JW , Plescia M , Ekwueme DU . Cancer 2014 120 Suppl 16 2537-9 Breast and cervical cancer have had disparate impact on the lives of women. The burden of breast and cervical cancer is more prominent among some racial and ethnic minority women. Providing comprehensive care to all medically underserved women is a critical element in continuing the battle to reduce cancer burden and eliminate disparities. The National Breast and Cervical Cancer Early Detection Program is the only nationally organized cancer screening program for underserved women in the United States. Its public health goal is to ensure access to high-quality screening, follow-up, and treatment services for diverse and vulnerable populations that, in turn, may reduce disparities. |
A chemical free, nanotechnology-based method for airborne bacterial inactivation using engineered water nanostructures
Pyrgiotakis G , McDevitt J , Bordini A , Diaz E , Molina R , Watson C , Deloid G , Lenard S , Fix N , Mizuyama Y , Yamauchi T , Brain J , Demokritou P . Environ Sci Nano 2014 1 (1) 15-26 Airborne pathogens are associated with the spread of infectious diseases and increased morbidity and mortality. Herein we present an emerging chemical free, nanotechnology-based method for airborne pathogen inactivation. This technique is based on transforming atmospheric water vapor into Engineered Water Nano-Structures (EWNS) via electrospray. The generated EWNS possess a unique set of physical, chemical, morphological and biological properties. Their average size is 25 nm and they contain reactive oxygen species (ROS) such as hydroxyl and superoxide radicals. In addition, EWNS are highly electrically charged (10 electrons per particle on average). A link between their electric charge and the reduction of their evaporation rate was illustrated resulting in an extended lifetime (over an hour) at room conditions. Furthermore, it was clearly demonstrated that the EWNS have the ability to interact with and inactivate airborne bacteria. Finally, inhaled EWNS were found to have minimal toxicological effects, as illustrated in an acute in-vivo inhalation study using a mouse model. In conclusion, this novel, chemical free, nanotechnology-based method has the potential to be used in the battle against airborne infectious diseases. |
CDC's winnable battles: improved nutrition, physical activity, and decreased obesity
Blanck HM , Collins J . Child Obes 2013 9 (6) 469-71 In fall 2010, the CDC, under Director Dr. Tom Frieden's leadership, identified six domestic winnable battles based on the magnitude of the public health burden and the ability to accelerate progress by expanding evidence-based practice.1 Nutrition, physical activity, and obesity along with food safety was identified as one of those battles in addition to human immunodeficiency virus, healthcare-associated infections, teen pregnancy, tobacco, and motor vehicle injuries. Since that time, the CDC has established 5-year goals, performance measures, and strategic plans for each winnable battle.2 Each battle area has identified optimal strategies and a process to leverage resources and partnerships to accelerate a measurable impact on health. CDC's current battle plan for nutrition, physical activity, and obesity focuses on working with partners in (1) improving maternity care practices to support women who choose to breastfeed, (2) reducing artificial transfat in the food supply, (3) reducing sodium in the food supply, (4) reducing consumption of calories from added sugars, and (5) improving the food, beverage, and activity environments of child care centers, schools, workplaces, and communities. Many of these focus areas and targets are also consistent with the nation's Healthy People 2020 objectives. |
High impact prevention and management strategies for improving outcomes in an HIV/AIDS population
Branson BM . J Manag Care Med 2013 16 (2) 63-65 The health care community continues to battle the HIV epidemic. The keys to preventing the spread of this infection are to screen those at risk and get them into treatment. All patients infected with HIV should receive antiretroviral therapy (AR T) to achieve viral suppression. Getting patients to adhere with therapy and stay in care should be major goals for managed care plans. |
From modest beginnings to a winnable battle: road safety efforts at CDC's Injury Center
Dellinger AM , Sleet DA . J Safety Res 2012 43 (4) 279-82 There are now more than 200 million licensed drivers, who drive an average of 13,000 miles per year on 4 million miles of roads. In 2010 crashes resulted in nearly 33,000 deaths and millions of nonfatal injuries. This article describes the Injury Center's response to this public health threat from our beginnings as a small Center in 1992, current motor vehicle injury prevention priorities, and emerging road safety issues that will need attention in the future. |
An outbreak of Plasmodium falciparum malaria in U.S. Marines deployed to Liberia
Whitman TJ , Coyne PE , Magill AJ , Blazes DL , Green MD , Milhous WK , Burgess TH , Freilich D , Tasker SA , Azar RG , Endy TP , Clagett CD , Deye GA , Shanks GD , Martin GJ . Am J Trop Med Hyg 2010 83 (2) 258-265 In 2003, 44 U.S. Marines were evacuated from Liberia with either confirmed or presumed Plasmodium falciparum malaria. An outbreak investigation showed that only 19 (45%) used insect repellent, 5 (12%) used permethrin-treated clothing, and none used bed netting. Adherence with weekly mefloquine (MQ) was reported by 23 (55%). However, only 4 (10%) had serum MQ levels high enough to correlate with protection (> 794 ng/mL), and 9 (22%) had evidence of steady-state kinetics (MQ carboxy metabolite/MQ > 3.79). Tablets collected from Marines met USP identity and dissolution specifications for MQ. Testing failed to identify P. falciparum isolates with MQ resistance. This outbreak resulted from under use of personal protective measures and inadequate adherence with chemophrophylaxis. It is essential that all international travelers make malaria prevention measures a priority, especially when embarking to regions of the world with high transmission intensity such as west Africa."Good doctors are of no use without good discipline. More than half the battle against disease is not fought by doctors, but by regimental officers. It is they who see that the daily dose of mepacrine (anti-malarial chemoprophylactic drug used in WW II) is taken...if mepacrine was not taken, I sacked the commander. I only had to sack three; by then the rest had got my meaning." -Lieutenant General William Slim (1891-1970), Burma Campaign, 1943. |
The 1918-1919 influenza pandemic in the United States: lessons learned and challenges exposed
Stern AM , Cetron MS , Markel H . Public Health Rep 2010 125 Suppl 3 6-8 Few have described the influenza pandemic of 1918–1919 better than Dr. Victor Clarence Vaughan, the portly dean of the University of Michigan Medical School and advisor to the U.S. Surgeon General during World War I. In early September 1918, upon surveying the destruction wrought not from bullets but rather from microbes at a military camp outside of Boston, Vaughan bemoaned that influenza had “… encircled the world, visited the remotest corners, taking toll of the most robust, sparing neither soldier nor civilian, and flaunting its red flag in the face of science.”1 Striding between the crowded, makeshift hospital wards and the overflowing morgue, Vaughan anxiously recorded that bodies were being stacked about “like cordwood.” | Vaughan's macabre image of the alarming and accelerating loss of thousands of young soldiers in the prime of their lives foreshadowed the overwhelming sickness and death that would engulf the globe in the fall of 1918, as the deadliest wave of this contagious calamity took its harrowing toll. After the pandemic subsided in the winter of 1920, at least 50 million people had died worldwide, including approximately 550,000 in the United States. It reached its height during the final months of “the war to end all wars,” which mobilized tens of millions of young men to the European theater of battle. Moreover, it appeared at a time when public health had made tremendous advances thanks to a combination of sanitarian campaigns and bacteriological science, but several decades before the viral etiology of influenza had been determined. |
Paul Baron (1944-2009)
Kulkarni P , Grinshpun SA , Turkevich LA , Schlecht PC , Birch ME , Willeke K . J Aerosol Sci 2009 40 (9) 731-32 Dr. Paul Andrew Baron died on May 20, 2009 at his residence in Cincinnati, OH, USA after a long battle with cancer. With his passing we have lost a leading scholar in aerosol science and occupational health research. |
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