Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 37 Records) |
Query Trace: Moses P[original query] |
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The Human Phenotype Ontology in 2024: phenotypes around the world
Gargano MA , Matentzoglu N , Coleman B , Addo-Lartey EB , Anagnostopoulos AV , Anderton J , Avillach P , Bagley AM , Bakštein E , Balhoff JP , Baynam G , Bello SM , Berk M , Bertram H , Bishop S , Blau H , Bodenstein DF , Botas P , Boztug K , Čady J , Callahan TJ , Cameron R , Carbon SJ , Castellanos F , Caufield JH , Chan LE , Chute CG , Cruz-Rojo J , Dahan-Oliel N , Davids JR , de Dieuleveult M , de Souza V , de Vries BBA , de Vries E , DePaulo JR , Derfalvi B , Dhombres F , Diaz-Byrd C , Dingemans AJM , Donadille B , Duyzend M , Elfeky R , Essaid S , Fabrizzi C , Fico G , Firth HV , Freudenberg-Hua Y , Fullerton JM , Gabriel DL , Gilmour K , Giordano J , Goes FS , Moses RG , Green I , Griese M , Groza T , Gu W , Guthrie J , Gyori B , Hamosh A , Hanauer M , Hanušová K , He YO , Hegde H , Helbig I , Holasová K , Hoyt CT , Huang S , Hurwitz E , Jacobsen JOB , Jiang X , Joseph L , Keramatian K , King B , Knoflach K , Koolen DA , Kraus ML , Kroll C , Kusters M , Ladewig MS , Lagorce D , Lai MC , Lapunzina P , Laraway B , Lewis-Smith D , Li X , Lucano C , Majd M , Marazita ML , Martinez-Glez V , McHenry TH , McInnis MG , McMurry JA , Mihulová M , Millett CE , Mitchell PB , Moslerová V , Narutomi K , Nematollahi S , Nevado J , Nierenberg AA , Čajbiková NN , Nurnberger JI Jr , Ogishima S , Olson D , Ortiz A , Pachajoa H , Perez de Nanclares G , Peters A , Putman T , Rapp CK , Rath A , Reese J , Rekerle L , Roberts AM , Roy S , Sanders SJ , Schuetz C , Schulte EC , Schulze TG , Schwarz M , Scott K , Seelow D , Seitz B , Shen Y , Similuk MN , Simon ES , Singh B , Smedley D , Smith CL , Smolinsky JT , Sperry S , Stafford E , Stefancsik R , Steinhaus R , Strawbridge R , Sundaramurthi JC , Talapova P , Tenorio Castano JA , Tesner P , Thomas RH , Thurm A , Turnovec M , van Gijn ME , Vasilevsky NA , Vlčková M , Walden A , Wang K , Wapner R , Ware JS , Wiafe AA , Wiafe SA , Wiggins LD , Williams AE , Wu C , Wyrwoll MJ , Xiong H , Yalin N , Yamamoto Y , Yatham LN , Yocum AK , Young AH , Yüksel Z , Zandi PP , Zankl A , Zarante I , Zvolský M , Toro S , Carmody LC , Harris NL , Munoz-Torres MC , Danis D , Mungall CJ , Köhler S , Haendel MA , Robinson PN . Nucleic Acids Res 2023 52 D1333-D1346 ![]() ![]() The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs. |
Improvement in infection prevention and control compliance at the three tertiary hospitals of Sierra Leone following an operational research study
Kamara RZ , Kamara IF , Moses F , Kanu JS , Kallon C , Kabba M , Moffett DB , Fofanah BD , Margao S , Kamara MN , Moiwo MM , Kpagoi Sstk , Tweya HM , Kumar AMV , Terry RF . Trop Med Infect Dis 2023 8 (7) Implementing infection prevention and control (IPC) programmes in line with the World Health Organization's (WHO) eight core components has been challenging in Sierra Leone. In 2021, a baseline study found that IPC compliance in three tertiary hospitals was sub-optimal. We aimed to measure the change in IPC compliance and describe recommended actions at these hospitals in 2023. This was a 'before and after' observational study using two routine cross-sectional assessments of IPC compliance using the WHO IPC Assessment Framework tool. IPC compliance was graded as inadequate (0-200), basic (201-400), intermediate (401-600), and advanced (601-800). The overall compliance scores for each hospital showed an improvement from 'Basic' in 2021 to 'Intermediate' in 2023, with a percentage increase in scores of 16.9%, 18.7%, and 26.9% in these hospitals. There was improved compliance in all core components, with the majority in the 'Intermediate' level for each hospital IPC programme. Recommended actions including the training of healthcare workers and revision of IPC guidelines were undertaken, but a dedicated IPC budget and healthcare-associated infection surveillance remained as gaps in 2023. Operational research is valuable in monitoring and improving IPC programme implementation. To reach the 'Advanced' level, these hospitals should establish a dedicated IPC budget and develop long-term implementation plans. |
Self-Reported Mask Use among Persons with or without SARS CoV-2 Vaccination -United States, December 2020-August 2021 (preprint)
Calamari LE , Weintraub WS , Santos R , Gibbs M , Bertoni AG , Ward LM , Saydah S , Plumb ID , Runyon MS , Wierzba TF , Sanders JW , Herrington D , Espeland MA , Williamson J , Mongraw-Chaffin M , Bertoni A , Alexander-Miller MA , Castri P , Mathews A , Munawar I , Seals AL , Ostasiewski B , Ballard CAP , Gurcan M , Ivanov A , Zapata GM , Westcott M , Blinson K , Blinson L , Mistysyn M , Davis D , Doomy L , Henderson P , Jessup A , Lane K , Levine B , McCanless J , McDaniel S , Melius K , O'Neill C , Pack A , Rathee R , Rushing S , Sheets J , Soots S , Wall M , Wheeler S , White J , Wilkerson L , Wilson R , Wilson K , Burcombe D , Saylor G , Lunn M , Ordonez K , O'Steen A , Wagner L , McCurdy LH , Gibbs MA , Taylor YJ , Calamari L , Tapp H , Ahmed A , Brennan M , Munn L , Dantuluri KL , Hetherington T , Lu LC , Dunn C , Hogg M , Price A , Leonidas M , Manning M , Rossman W , Gohs FX , Harris A , Priem JS , Tochiki P , Wellinsky N , Silva C , Ludden T , Hernandez J , Spencer K , McAlister L , Weintraub W , Miller K , Washington C , Moses A , Dolman S , Zelaya-Portillo J , Erkus J , Blumenthal J , Romero Barrientos RE , Bennett S , Shah S , Mathur S , Boxley C , Kolm P , Franklin E , Ahmed N , Larsen M , Oberhelman R , Keating J , Kissinger P , Schieffelin J , Yukich J , Beron A , Teigen J , Kotloff K , Chen WH , Friedman-Klabanoff D , Berry AA , Powell H , Roane L , Datar R , Correa A , Navalkele B , Min YI , Castillo A , Ward L , Santos RP , Anugu P , Gao Y , Green J , Sandlin R , Moore D , Drake L , Horton D , Johnson KL , Stover M , Lagarde WH , Daniel L , Maguire PD , Hanlon CL , McFayden L , Rigo I , Hines K , Smith L , Harris M , Lissor B , Cook V , Eversole M , Herrin T , Murphy D , Kinney L , Diehl P , Abromitis N , Pierre TSt , Heckman B , Evans D , March J , Whitlock B , Moore W , Arthur S , Conway J , Gallaher TR , Johanson M , Brown S , Dixon T , Reavis M , Henderson S , Zimmer M , Oliver D , Jackson K , Menon M , Bishop B , Roeth R , King-Thiele R , Hamrick TS , Ihmeidan A , Hinkelman A , Okafor C , Bray Brown RB , Brewster A , Bouyi D , Lamont K , Yoshinaga K , Vinod P , Peela AS , Denbel G , Lo J , Mayet-Khan M , Mittal A , Motwani R , Raafat M , Schultz E , Joseph A , Parkeh A , Patel D , Afridi B , Uschner D , Edelstein SL , Santacatterina M , Strylewicz G , Burke B , Gunaratne M , Turney M , Zhou SQ , Tjaden AH , Fette L , Buahin A , Bott M , Graziani S , Soni A , Mores C , Porzucek A , Laborde R , Acharya P , Guill L , Lamphier D , Schaefer A , Satterwhite WM , McKeague A , Ward J , Naranjo DP , Darko N , Castellon K , Brink R , Shehzad H , Kuprianov D , McGlasson D , Hayes D , Edwards S , Daphnis S , Todd B , Goodwin A , Berkelman R , Hanson K , Zeger S , Hopkins J , Reilly C , Edwards K , Gayle H , Redd S . medRxiv 2022 10 Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
RSV among American Indian and Alaska Native children: 2019 to 2020
Atwell JE , Hartman RM , Parker D , Taylor K , Brown LB , Sandoval M , Ritchie N , Desnoyers C , Wilson AS , Hammes M , Tiesinga J , Halasa N , Langley G , Prill MM , Bruden D , Close R , Moses J , Karron RA , Santosham M , Singleton RJ , Hammitt LL . Pediatrics 2023 152 (2) Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infections, including bronchiolitis and pneumonia, in children under 5 years of age globally.1 Historically, RSV-associated hospitalization rates among American Indian and Alaska Native (AI/AN) children have been among the highest in the world.2,–7 Contemporary estimates of RSV-acute respiratory infection (ARI) are needed to inform RSV prevention strategies for AI/AN children. |
Neural tube defects as a cause of death among stillbirths, infants, and children younger than 5 years in sub-Saharan Africa and southeast Asia: an analysis of the CHAMPS network
Madrid L , Vyas KJ , Kancherla V , Leulseged H , Suchdev PS , Bassat Q , Sow SO , El Arifeen S , Madhi SA , Onyango D , Ogbuanu I , Scott JAG , Blau D , Mandomando I , Keita AM , Gurley ES , Mahtab S , Akelo V , Sannoh S , Tilahun Y , Varo R , Onwuchekwa U , Rahman A , Adam Y , Omore R , Lako S , Xerinda E , Islam KM , Wise A , Tippet-Barr BA , Kaluma E , Ajanovic S , Kotloff KL , Hossain MZ , Mutevedzi P , Tapia MD , Rogena E , Moses F , Whitney CG , Assefa N . Lancet Glob Health 2023 11 (7) e1041-e1052 BACKGROUND: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia. METHODS: This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site. FINDINGS: Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site. INTERPRETATION: CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects. FUNDING: Bill & Melinda Gates Foundation. |
COVID-19 Case Investigation and Contact Tracing in the US, 2020.
Lash RR , Moonan PK , Byers BL , Bonacci RA , Bonner KE , Donahue M , Donovan CV , Grome HN , Janssen JM , Magleby R , McLaughlin HP , Miller JS , Pratt CQ , Steinberg J , Varela K , Anschuetz GL , Cieslak PR , Fialkowski V , Fleischauer AT , Goddard C , Johnson SJ , Morris M , Moses J , Newman A , Prinzing L , Sulka AC , Va P , Willis M , Oeltmann JE . JAMA Netw Open 2021 4 (6) e2115850 IMPORTANCE: Contact tracing is a multistep process to limit SARS-CoV-2 transmission. Gaps in the process result in missed opportunities to prevent COVID-19. OBJECTIVE: To quantify proportions of cases and their contacts reached by public health authorities and the amount of time needed to reach them and to compare the risk of a positive COVID-19 test result between contacts and the general public during 4-week assessment periods. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study took place at 13 health departments and 1 Indian Health Service Unit in 11 states and 1 tribal nation. Participants included all individuals with laboratory-confirmed COVID-19 and their named contacts. Local COVID-19 surveillance data were used to determine the numbers of persons reported to have laboratory-confirmed COVID-19 who were interviewed and named contacts between June and October 2020. MAIN OUTCOMES AND MEASURES: For contacts, the numbers who were identified, notified of their exposure, and agreed to monitoring were calculated. The median time from index case specimen collection to contact notification was calculated, as were numbers of named contacts subsequently notified of their exposure and monitored. The prevalence of a positive SARS-CoV-2 test among named and tested contacts was compared with that jurisdiction's general population during the same 4 weeks. RESULTS: The total number of cases reported was 74 185. Of these, 43 931 (59%) were interviewed, and 24 705 (33%) named any contacts. Among the 74 839 named contacts, 53 314 (71%) were notified of their exposure, and 34 345 (46%) agreed to monitoring. A mean of 0.7 contacts were reached by telephone by public health authorities, and only 0.5 contacts per case were monitored. In general, health departments reporting large case counts during the assessment (≥5000) conducted smaller proportions of case interviews and contact notifications. In 9 locations, the median time from specimen collection to contact notification was 6 days or less. In 6 of 8 locations with population comparison data, positive test prevalence was higher among named contacts than the general population. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US local COVID-19 surveillance data, testing named contacts was a high-yield activity for case finding. However, this assessment suggests that contact tracing had suboptimal impact on SARS-CoV-2 transmission, largely because 2 of 3 cases were either not reached for interview or named no contacts when interviewed. These findings are relevant to decisions regarding the allocation of public health resources among the various prevention strategies and for the prioritization of case investigations and contact tracing efforts. |
Do monkeypox exposures vary by ethnicity Comparison of Aka- and Bantu-suspected monkeypox cases
Guagliardo SAJ , Doshi RH , Reynolds MG , Dzabatou-Babeaux A , Ndakala N , Moses C , McCollum AM , Petersen BW . Am J Trop Med Hyg 2019 102 (1) 202-205 In 2017, a monkeypox outbreak occurred in Likouala Department, Republic of the Congo. Many of the affected individuals were of Aka ethnicity, hunter-gatherers indigenous to Central Africa who have worse health outcomes in comparison with other forest-dwelling peoples. To test the hypothesis that Aka people have different risk factors for monkeypox, we analyzed questionnaire data for 39 suspected cases, comparing Aka and Bantu groups. Aka people were more likely to touch animal urine/feces, find dead animals in/around the home, eat an animal that was found dead, or to have been scratched or bitten by an animal (P < 0.05, all variables). They were also more likely to visit the forest >/= once/week, sleep outside, or sleep on the ground (P < 0.001, all variables), providing opportunities for contact with monkeypox reservoirs during the night. The Aka and possibly other vulnerable groups may warrant special attention during educational and health promotion programs. |
The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis.
Commons RJ , Simpson JA , Thriemer K , Abreha T , Adam I , Anstey NM , Assefa A , Awab GR , Baird JK , Barber BE , Chu CS , Dahal P , Daher A , Davis TME , Dondorp AM , Grigg MJ , Humphreys GS , Hwang J , Karunajeewa H , Laman M , Lidia K , Moore BR , Mueller I , Nosten F , Pasaribu AP , Pereira DB , Phyo AP , Poespoprodjo JR , Sibley CH , Stepniewska K , Sutanto I , Thwaites G , Hien TT , White NJ , William T , Woodrow CJ , Guerin PJ , Price RN . PLoS Med 2019 16 (10) e1002928 ![]() BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax. METHODS AND FINDINGS: Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups. CONCLUSIONS: In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis. |
Strengthening healthcare workforce capacity during and post Ebola outbreaks in Liberia: an innovative and effective approach to epidemic preparedness and response
Bemah P , Baller A , Cooper C , Massaquoi M , Skrip L , Rude JM , Twyman A , Moses P , Seifeldin R , Udhayashankar K , Enrique K , Niescierenko M , Owen C , Brown L , Boukare B , Williams D , Nyenswah T , Kateh F , Dahn B , Gasasira A , Fall IS . Pan Afr Med J 2019 33 9 Introduction: The 2014-2016 Ebola virus disease (EVD) outbreak in Liberia highlighted the importance of robust preparedness measures for a well-coordinated response; the initially delayed response contributed to the steep incidence of cases, infections among health care workers, and a collapse of the health care system. To strengthen local capacity and combat disease transmission, various healthcare worker (HCW) trainings, including the Ebola treatment unit (ETU) training, safe & quality services (SQS) training and rapid response team (RRT), were developed and implemented between 2014 and 2017. Methods: Data from the ETU, SQS and RRT trainings were analyzed to determine knowledge and confidence gained. Results: The ETU, SQS and RRT training were completed by a total of 21,248 participants. There were improvements in knowledge and confidence, an associated reduction in HCWs infection and reduced response time to subsequent public health events. Conclusion: No infections were reported by healthcare workers in Liberia since the completion of these training programs. HCW training programmes initiated during and post disease outbreak can boost public trust in the health system while providing an entry point for establishing an Epidemic Preparedness and Response (EPR) framework in resource-limited settings. |
Human monkeypox in Sierra Leone after 44-year absence of reported cases
Reynolds MG , Wauquier N , Li Y , Satheshkumar PS , Kanneh LD , Monroe B , Maikere J , Saffa G , Gonzalez JP , Fair J , Carroll DS , Jambai A , Dafae F , Khan SH , Moses LM . Emerg Infect Dis 2019 25 (5) 1023-1025 We note the reemergence of human monkeypox in Sierra Leone following a 44-year absence of reported disease. The persons affected were an 11-month-old boy and, several years later, a 35-year-old man. The reappearance of monkeypox in this country suggests a need for renewed vigilance and awareness of the disease and its manifestations. |
New filovirus disease classification and nomenclature.
Kuhn JH , Adachi T , Adhikari NKJ , Arribas JR , Bah IE , Bausch DG , Bhadelia N , Borchert M , Brantsaeter AB , Brett-Major DM , Burgess TH , Chertow DS , Chute CG , Cieslak TJ , Colebunders R , Crozier I , Davey RT , de Clerck H , Delgado R , Evans L , Fallah M , Fischer WA 2nd , Fletcher TE , Fowler RA , Grunewald T , Hall A , Hewlett A , Hoepelman AIM , Houlihan CF , Ippolito G , Jacob ST , Jacobs M , Jakob R , Jacquerioz FA , Kaiser L , Kalil AC , Kamara RF , Kapetshi J , Klenk HD , Kobinger G , Kortepeter MG , Kraft CS , Kratz T , Bosa HSK , Lado M , Lamontagne F , Lane HC , Lobel L , Lutwama J , Lyon GM 3rd , Massaquoi MBF , Massaquoi TA , Mehta AK , Makuma VM , Murthy S , Musoke TS , Muyembe-Tamfum JJ , Nakyeyune P , Nanclares C , Nanyunja M , Nsio-Mbeta J , O'Dempsey T , Paweska JT , Peters CJ , Piot P , Rapp C , Renaud B , Ribner B , Sabeti PC , Schieffelin JS , Slenczka W , Soka MJ , Sprecher A , Strong J , Swanepoel R , Uyeki TM , van Herp M , Vetter P , Wohl DA , Wolf T , Wolz A , Wurie AH , Yoti Z . Nat Rev Microbiol 2019 17 (5) 261-263 ![]() ![]() The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision. |
Introduction of Ebola virus into a remote border district of Sierra Leone, 2014: use of field epidemiology and RNA sequencing to describe chains of transmission.
DeSilva MB , Styles T , Basler C , Moses FL , Husain F , Reichler M , Whitmer S , McAuley J , Belay E , Friedman M , Muoghalu IS , Swaray P , Stroher U , Redd JT . Epidemiol Infect 2019 147 e88 ![]() ![]() In early October 2014, 7 months after the 2014-2015 Ebola epidemic in West Africa began, a cluster of reported deaths in Koinadugu, a remote district of Sierra Leone, was the first evidence of Ebola virus disease (Ebola) in the district. Prior to this event, geographic isolation was thought to have prevented the introduction of Ebola to this area. We describe our initial investigation of this cluster of deaths and subsequent public health actions after Ebola was confirmed, and present challenges to our investigation and methods of overcoming them. We present a transmission tree and results of whole genome sequencing of selected isolates to identify the source of infection in Koinadugu and demonstrate transmission between its villages. Koinadugu's experience highlights the danger of assuming that remote location and geographic isolation can prevent the spread of Ebola, but also demonstrates how deployment of rapid field response teams can help limit spread once Ebola is detected. |
Epidemiologic and ecologic investigations of monkeypox, Likouala Department, Republic of the Congo, 2017
Doshi RH , Guagliardo SAJ , Doty JB , Babeaux AD , Matheny A , Burgado J , Townsend MB , Morgan CN , Satheshkumar PS , Ndakala N , Kanjingankolo T , Kitembo L , Malekani J , Kalemba L , Pukuta E , N'Kaya T , Kangoula F , Moses C , McCollum AM , Reynolds MG , Mombouli JV , Nakazawa Y , Petersen BW . Emerg Infect Dis 2019 25 (2) 281-289 Monkeypox, caused by a zoonotic orthopoxvirus, is endemic in Central and West Africa. Monkeypox has been sporadically reported in the Republic of the Congo. During March 22-April 5, 2017, we investigated 43 suspected human monkeypox cases. We interviewed suspected case-patients and collected dried blood strips and vesicular and crust specimens (active lesions), which we tested for orthopoxvirus antibodies by ELISA and monkeypox virus and varicella zoster virus DNA by PCR. An ecologic investigation was conducted around Manfouete, and specimens from 105 small mammals were tested for anti-orthopoxvirus antibodies or DNA. Among the suspected human cases, 22 met the confirmed, probable, and possible case definitions. Only 18 patients had available dried blood strips; 100% were IgG positive, and 88.9% (16/18) were IgM positive. Among animals, only specimens from Cricetomys giant pouched rats showed presence of orthopoxvirus antibodies, adding evidence to this species' involvement in the transmission and maintenance of monkeypox virus in nature. |
Strengthening of surveillance during monkeypox outbreak, Republic of the Congo, 2017
Doshi RH , Guagliardo SAJ , Dzabatou-Babeaux A , Likouayoulou C , Ndakala N , Moses C , Olson V , McCollum AM , Petersen BW . Emerg Infect Dis 2018 24 (6) 1158-1160 Reports of 10 suspected cases of monkeypox in Likouala Department, Republic of the Congo, triggered an investigation and response in March 2017 that included community education and surveillance strengthening. Increasing numbers of outbreaks suggest that monkeypox virus is becoming a more prevalent human pathogen. Diverse approaches are necessary for disease control and prevention. |
Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening.
Raftery P , Condell O , Wasunna C , Kpaka J , Zwizwai R , Nuha M , Fallah M , Freeman M , Harris V , Miller M , Baller A , Massaquoi M , Katawera V , Saindon J , Bemah P , Hamblion E , Castle E , Williams D , Gasasira A , Nyenswah T . PLoS Negl Trop Dis 2018 12 (1) e0006135 ![]() ![]() The 2014-16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64-100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be integrated into other national diagnostic algorithms. The technology has on average a 2-hour sample-to-result time and allows for single specimen testing to overcome potential delays of batching. This model of a mobile laboratory equipped with Xpert Ebola test, staffed by local laboratory technicians, could serve to strengthen outbreak preparedness and response for future outbreaks of EVD in Liberia and the region. |
Evolution and current understanding of physicochemical characterization of particulate matter from reactivity controlled compression ignition combustion on a multicylinder light-duty engine
Storey JME , Curran SJ , Lewis SA , Barone TL , Dempsey AB , Moses-Debusk M , Hanson RM , Prikhodko VY , Northrop WF . Int J Engine Res 2017 18 505-519 Low-temperature compression ignition combustion can result in nearly smokeless combustion, as indicated by a smoke meter or other forms of soot measurement that rely on absorbance due to elemental carbon content. Highly premixed low-temperature combustion modes do not form particulate matter in the traditional pathways seen with conventional diesel combustion. Previous research into reactivity controlled compression ignition particulate matter has shown, despite a near zero smoke number, significant mass can be collected on filter media used for particulate matter certification measurement. In addition, particulate matter size distributions reveal that a fraction of the particles survive heated double-dilution conditions. This study summarizes research completed at Oak Ridge National Laboratory to date on characterizing the nature, chemistry and aftertreatment considerations of reactivity controlled compression ignition particulate matter and presents new research highlighting the importance of injection strategy and fuel composition on reactivity controlled compression ignition particulate matter formation. Particle size measurements and the transmission electron microscopy results do show the presence of soot particles; however, the elemental carbon fraction was, in many cases, within the uncertainty of the thermal-optical measurement. Particulate matter emitted during reactivity controlled compression ignition operation was also collected with a novel sampling technique and analyzed by thermal desorption or pyrolysis gas chromatography mass spectroscopy. Particulate matter speciation results indicated that the high boiling range of diesel hydrocarbons was likely responsible for the particulate matter mass captured on the filter media. To investigate potential fuel chemistry effects, either ethanol or biodiesel were incorporated to assess whether oxygenated fuels may enhance particle emission reduction. © 2016 IMechE. |
Ebola Virus RNA in Semen from an HIV-Positive Survivor of Ebola.
Purpura LJ , Rogers E , Baller A , White S , Soka M , Choi MJ , Mahmoud N , Wasunna C , Massaquoi M , Kollie J , Dweh S , Bemah P , Ladele V , Kpaka J , Jawara M , Mugisha M , Subah O , Faikai M , Bailey JA , Rollin P , Marston B , Nyenswah T , Gasasira A , Knust B , Nichol S , Williams D . Emerg Infect Dis 2017 23 (4) 714-715 ![]() Ebola virus is known to persist in semen of male survivors of Ebola virus disease (EVD). However, maximum duration of, or risk factors for, virus persistence are unknown. We report an EVD survivor with preexisting HIV infection, whose semen was positive for Ebola virus RNA 565 days after recovery from EVD. |
Multi-center evaluation of one commercial and 12 in-house real-time PCR assays for detection of Mycoplasma pneumoniae.
Dumke R , Benitez AJ , Chalker V , Gullsby K , Henrich B , Hidalgo-Grass C , Hoogenboezem T , Kese D , Loens K , Maaskant J , Michael-Gayego A , Moses AE , Nir-Paz R , Pas SD , Pereyre S , Petersen RF , Rosenblatt M , van Rossum AM , Uldum SA , Unger WW , Ursi D , Winchell JM , Bebear C . Diagn Microbiol Infect Dis 2017 88 (2) 111-114 ![]() Detection of Mycoplasma pneumoniae by real-time PCR is not yet standardized across laboratories. We have implemented a standardization protocol to compare the performance of thirteen commercial and in-house approaches. Despite differences on threshold values of samples, all assays were able to detect at least 20M. pneumoniae genomes per reaction. |
Presumptive risk factors for monkeypox in rural communities in the Democratic Republic of the Congo
Quiner CA , Moses C , Monroe BP , Nakazawa Y , Doty JB , Hughes CM , McCollum AM , Ibata S , Malekani J , Okitolonda E , Carroll DS , Reynolds MG . PLoS One 2017 12 (2) e0168664 Monkeypox virus (MPXV), a close relative of Variola virus, is a zoonotic virus with an unknown reservoir. Interaction with infected wildlife, bites from peri-domestic animals, and bushmeat hunting are hypothesized routes of infection from wildlife to humans. Using a Risk Questionnaire, performed in monkeypox-affected areas of rural Democratic Republic of the Congo, we describe the lifestyles and demographics associated with presumptive risk factors for MPXV infection. We generated two indices to assess risk: Household Materials Index (HMI), a proxy for socioeconomic status of households and Risk Activity Index (RAI), which describes presumptive risk for animal-to-human transmission of MPXV. Based on participant self-reported activity patterns, we found that people in this population are more likely to visit the forest than a market to fulfill material needs, and that the reported occupation is limited in describing behavior of individuals may participate. Being bitten by rodents in the home was commonly reported, and this was significantly associated with a low HMI. The highest scoring RAI sub-groups were 'hunters' and males aged ≥ 18 years; however, several activities involving MPXV-implicated animals were distributed across all sub-groups. The current analysis may be useful in identifying at-risk groups and help to direct education, outreach and prevention efforts more efficiently. |
Prevention of sexual transmission of Ebola in Liberia through a national semen testing and counselling programme for survivors: an analysis of Ebola virus RNA results and behavioural data.
Soka MJ , Choi MJ , Baller A , White S , Rogers E , Purpura LJ , Mahmoud N , Wasunna C , Massaquoi M , Abad N , Kollie J , Dweh S , Bemah PK , Christie A , Ladele V , Subah OC , Pillai S , Mugisha M , Kpaka J , Kowalewski S , German E , Stenger M , Nichol S , Stroher U , Vanderende KE , Zarecki SM , Green HH , Bailey JA , Rollin P , Marston B , Nyenswah TG , Gasasira A , Knust B , Williams D . Lancet Glob Health 2016 4 (10) e736-43 ![]() BACKGROUND: Ebola virus has been detected in semen of Ebola virus disease survivors after recovery. Liberia's Men's Health Screening Program (MHSP) offers Ebola virus disease survivors semen testing for Ebola virus. We present preliminary results and behavioural outcomes from the first national semen testing programme for Ebola virus. METHODS: The MHSP operates out of three locations in Liberia: Redemption Hospital in Montserrado County, Phebe Hospital in Bong County, and Tellewoyan Hospital in Lofa County. Men aged 15 years and older who had an Ebola treatment unit discharge certificate are eligible for inclusion. Participants' semen samples were tested for Ebola virus RNA by real-time RT-PCR and participants received counselling on safe sexual practices. Participants graduated after receiving two consecutive negative semen tests. Counsellors collected information on sociodemographics and sexual behaviours using questionnaires administered at enrolment, follow up, and graduation visits. Because the programme is ongoing, data analysis was restricted to data obtained from July 7, 2015, to May 6, 2016. FINDINGS: As of May 6, 2016, 466 Ebola virus disease survivors had enrolled in the programme; real-time RT-PCR results were available from 429 participants. 38 participants (9%) produced at least one semen specimen that tested positive for Ebola virus RNA. Of these, 24 (63%) provided semen specimens that tested positive 12 months or longer after Ebola virus disease recovery. The longest interval between discharge from an Ebola treatment unit and collection of a positive semen sample was 565 days. Among participants who enrolled and provided specimens more than 90 days since their Ebola treatment unit discharge, men older than 40 years were more likely to have a semen sample test positive than were men aged 40 years or younger (p=0.0004). 84 (74%) of 113 participants who reported not using a condom at enrolment reported using condoms at their first follow-up visit (p<0.0001). 176 (46%) of 385 participants who reported being sexually active at enrolment reported abstinence at their follow-up visit (p<0.0001). INTERPRETATION: Duration of detection of Ebola virus RNA by real-time RT-PCR varies by individual and might be associated with age. By combining behavioural counselling and laboratory testing, the Men's Health Screening Program helps male Ebola virus disease survivors understand their individual risk and take appropriate measures to protect their sexual partners. FUNDING: World Health Organization and the US Centers for Disease Control and Prevention. |
Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus-Infected Patients.
Rosenke K , Adjemian J , Munster VJ , Marzi A , Falzarano D , Onyango CO , Ochieng M , Juma B , Fischer RJ , Prescott JB , Safronetz D , Omballa V , Owuor C , Hoenen T , Groseth A , Martellaro C , van Doremalen N , Zemtsova G , Self J , Bushmaker T , McNally K , Rowe T , Emery SL , Feldmann F , Williamson BN , Best SM , Nyenswah TG , Grolla A , Strong JE , Kobinger G , Bolay FK , Zoon KC , Stassijns J , Giuliani R , de Smet M , Nichol ST , Fields B , Sprecher A , Massaquoi M , Feldmann H , de Wit E . Clin Infect Dis 2016 63 (8) 1026-33 ![]() BACKGROUND: The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. METHODS: All blood samples from suspected Ebola virus-infected patients admitted to the Medecins Sans Frontieres ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. RESULTS: The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. CONCLUSIONS: Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection. |
Reduced evolutionary rate in reemerged Ebola virus transmission chains.
Blackley DJ , Wiley MR , Ladner JT , Fallah M , Lo T , Gilbert ML , Gregory C , D'Ambrozio J , Coulter S , Mate S , Balogun Z , Kugelman J , Nwachukwu W , Prieto K , Yeiah A , Amegashie F , Kearney B , Wisniewski M , Saindon J , Schroth G , Fakoli L , Diclaro JW 2nd , Kuhn JH , Hensley LE , Jahrling PB , Stroher U , Nichol ST , Massaquoi M , Kateh F , Clement P , Gasasira A , Bolay F , Monroe SS , Rambaut A , Sanchez-Lockhart M , Scott Laney A , Nyenswah T , Christie A , Palacios G . Sci Adv 2016 2 (4) e1600378 ![]() On 29 June 2015, Liberia's respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak ("flare-up") of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over. |
Evaluation of multiplex-based antibody testing for use in large scale surveillance for yaws: a comparative study
Cooley GM , Mitja O , Goodhew B , Pillay A , Lammie PJ , Castro A , Moses P , Chen C , Ye T , Ballard R , Martin DL . J Clin Microbiol 2016 54 (5) 1321-5 BACKGROUND: WHO has targeted yaws for global eradication by 2020. Program goals are to achieve interruption of transmission in endemic countries and to certify previously-endemic countries as yaws-free. No new rapid plasmin reagin (RPR) sero-reactivity in young children is required for certification of elimination at a country level. We sought to evaluate if antibody responses to specific treponemal antigens measured in a high-throughput multiplex bead array (MBA) assay differentiate past versus current infection, and whether a non-treponemal, lipoidal antigen test could be incorporated into the MBA. METHODS: Serum and dried blood spot specimens collected for yaws surveillance projects in Ghana, Vanuatu, and Papua New Guinea were run on MBA to measure antibodies against recombinant p17 (rp17) and TmpA treponemal antigens. Results were compared to standard treponemal laboratory (TPPA or TPHA; "TPP(H)A ") and quantitative RPR test data. FINDINGS: Of 589 specimens, 241 were TPP(H)A+/RPR+, 88 were TPP(H)A+/RPR-, 6 were TPP(H)A -/RPR+ and 254 were negative for both tests. Compared to TPP(H)A, reactive concordance of rp17 was 93.7%, while reactive concordance of TmpA was only 81.9%. TmpA-specific reactivity showed good correlation with RPR titers (R2 = 0.41, p<0.0001). IgG responses to the lipoidal antigen used in RPR testing (cardiolipin) were not detected in the MBA. INTERPRETATION: Our results suggest that TmpA can be used as a treponemal antigen marker for recent or active infection and potentially replace RPR in. a high-throughput multiplex tool for large-scale yaws surveillance. |
Nanopore Sequencing as a Rapidly Deployable Ebola Outbreak Tool.
Hoenen T , Groseth A , Rosenke K , Fischer RJ , Hoenen A , Judson SD , Martellaro C , Falzarano D , Marzi A , Squires RB , Wollenberg KR , de Wit E , Prescott J , Safronetz D , van Doremalen N , Bushmaker T , Feldmann F , McNally K , Bolay FK , Fields B , Sealy T , Rayfield M , Nichol ST , Zoon KC , Massaquoi M , Munster VJ , Feldmann H . Emerg Infect Dis 2016 22 (2) 331-4 ![]() Rapid sequencing of RNA/DNA from pathogen samples obtained during disease outbreaks provides critical scientific and public health information. However, challenges exist for exporting samples to laboratories or establishing conventional sequencers in remote outbreak regions. We successfully used a novel, pocket-sized nanopore sequencer at a field diagnostic laboratory in Liberia during the current Ebola virus outbreak. |
Molecular Evidence of Sexual Transmission of Ebola Virus.
Mate SE , Kugelman JR , Nyenswah TG , Ladner JT , Wiley MR , Cordier-Lassalle T , Christie A , Schroth GP , Gross SM , Davies-Wayne GJ , Shinde SA , Murugan R , Sieh SB , Badio M , Fakoli L , Taweh F , de Wit E , van Doremalen N , Munster VJ , Pettitt J , Prieto K , Humrighouse BW , Stroher U , DiClaro JW , Hensley LE , Schoepp RJ , Safronetz D , Fair J , Kuhn JH , Blackley DJ , Laney AS , Williams DE , Lo T , Gasasira A , Nichol ST , Formenty P , Kateh FN , De Cock KM , Bolay F , Sanchez-Lockhart M , Palacios G . N Engl J Med 2015 373 (25) 2448-54 ![]() A suspected case of sexual transmission from a male survivor of Ebola virus disease (EVD) to his female partner (the patient in this report) occurred in Liberia in March 2015. Ebola virus (EBOV) genomes assembled from blood samples from the patient and a semen sample from the survivor were consistent with direct transmission. The genomes shared three substitutions that were absent from all other Western African EBOV sequences and that were distinct from the last documented transmission chain in Liberia before this case. Combined with epidemiologic data, the genomic analysis provides evidence of sexual transmission of EBOV and evidence of the persistence of infective EBOV in semen for 179 days or more after the onset of EVD. (Funded by the Defense Threat Reduction Agency and others.). |
Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.
Park DJ , Dudas G , Wohl S , Goba A , Whitmer SL , Andersen KG , Sealfon RS , Ladner JT , Kugelman JR , Matranga CB , Winnicki SM , Qu J , Gire SK , Gladden-Young A , Jalloh S , Nosamiefan D , Yozwiak NL , Moses LM , Jiang PP , Lin AE , Schaffner SF , Bird B , Towner J , Mamoh M , Gbakie M , Kanneh L , Kargbo D , Massally JL , Kamara FK , Konuwa E , Sellu J , Jalloh AA , Mustapha I , Foday M , Yillah M , Erickson BR , Sealy T , Blau D , Paddock C , Brault A , Amman B , Basile J , Bearden S , Belser J , Bergeron E , Campbell S , Chakrabarti A , Dodd K , Flint M , Gibbons A , Goodman C , Klena J , McMullan L , Morgan L , Russell B , Salzer J , Sanchez A , Wang D , Jungreis I , Tomkins-Tinch C , Kislyuk A , Lin MF , Chapman S , MacInnis B , Matthews A , Bochicchio J , Hensley LE , Kuhn JH , Nusbaum C , Schieffelin JS , Birren BW , Forget M , Nichol ST , Palacios GF , Ndiaye D , Happi C , Gevao SM , Vandi MA , Kargbo B , Holmes EC , Bedford T , Gnirke A , Stroher U , Rambaut A , Garry RF , Sabeti PC . Cell 2015 161 (7) 1516-26 ![]() The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. |
Collection and utilization of animal carcasses associated with zoonotic disease in Tshuapa District, the Democratic Republic of the Congo, 2012
Monroe BP , Doty JB , Moses C , Ibata S , Reynolds M , Carroll D . J Wildl Dis 2015 51 (3) 734-8 The collection and consumption of animal carcasses is a common activity in forested areas of the Congo River basin and creates sustainability, conservation, and health concerns. Residents of the Tshuapa District reported collecting the remains of 5,878 animals from >30 species when surveyed about their wildlife consumption habits. Carcasses were discovered in varying degrees of decomposition and were often consumed at home or sold in local markets. The most commonly collected animals were Cricetomys gambianus (giant pouched rat), Cercopithecus ascanius (red-tailed monkey), and Heliosciurus rufobrachium (red-legged sun squirrel). Many of the species recorded may be hosts of zoonotic pathogens, creating concern for spillover events. |
Nomenclature- and database-compatible names for the two Ebola virus variants that emerged in Guinea and the Democratic Republic of the Congo in 2014
Kuhn JH , Andersen KG , Baize S , Bao Y , Bavari S , Berthet N , Blinkova O , Brister JR , Clawson AN , Fair J , Gabriel M , Garry RF , Gire SK , Goba A , Gonzalez JP , Gunther S , Happi CT , Jahrling PB , Kapetshi J , Kobinger G , Kugelman JR , Leroy EM , Maganga GD , Mbala PK , Moses LM , Muyembe-Tamfum JJ , N'Faly M , Nichol ST , Omilabu SA , Palacios G , Park DJ , Paweska JT , Radoshitzky SR , Rossi CA , Sabeti PC , Schieffelin JS , Schoepp RJ , Sealfon R , Swanepoel R , Towner JS , Wada J , Wauquier N , Yozwiak NL , Formenty P . Viruses 2014 6 (11) 4760-99 ![]() In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: "Makona", Middle Africa: "Lomela") and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures. |
Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children.
Conrad MD , LeClair N , Arinaitwe E , Wanzira H , Kakuru A , Bigira V , Muhindo M , Kamya MR , Tappero JW , Greenhouse B , Dorsey G , Rosenthal PJ . J Infect Dis 2014 210 (3) 344-53 ![]() BACKGROUND: Artemisinin-based combination therapies, including artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), are recommended to treat uncomplicated falciparum malaria. Sensitivities to components of AL and DP are impacted by polymorphisms in pfmdr1 and pfcrt. We monitored changes in prevalences of polymorphisms in Tororo, Uganda, from 2008 to 2012. METHODS: Polymorphic loci in pfmdr1 and pfcrt were characterized in samples from 312 children randomized to AL or DP for each episode of uncomplicated malaria (50 samples per arm for each 3-month interval) utilizing a fluorescent microsphere assay. Treatment outcomes and impacts of prior therapies were also characterized. RESULTS: Prevalence increased significantly over time for pfmdr1 N86 (AL: odds ratio [OR], 2.08 [95% confidence interval {CI}, 1.83-2.38]; DP: 1.41 [95% CI, 1.25-1.57]), pfmdr1 D1246 (AL: 1.46 [95% CI, 1.29-1.64]; DP: 1.36 [95% CI, 1.23-1.50]), and pfcrt K76 (AL: 3.37 [95% CI, 1.85-6.16]; DP: 5.84 [95% CI, 1.94-17.53], and decreased for pfmdr1 Y184 (AL: 0.78 [95% CI, .70-.86]; DP: 0.84 [95% CI, .76-1.50]); changes were consistently greater in the AL arm. Recent AL treatment selected for pfmdr1 N86, D1246, and 184F in subsequent episodes; DP selected for the opposite alleles. CONCLUSIONS: Genotypes with decreased sensitivity to AL components increased over time. This increase was greater in children receiving AL, suggesting that the choice of treatment regimen can profoundly influence parasite genetics and drug sensitivity. CLINICAL TRIALS REGISTRATION: NCT00527800. |
Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda.
Mbogo GW , Nankoberanyi S , Tukwasibwe S , Baliraine FN , Nsobya SL , Conrad MD , Arinaitwe E , Kamya M , Tappero J , Staedke SG , Dorsey G , Greenhouse B , Rosenthal PJ . Am J Trop Med Hyg 2014 91 (1) 54-61 ![]() Standard therapy for malaria in Uganda changed from chloroquine to chloroquine + sulfadoxine-pyrimethamine in 2000, and artemether-lumefantrine in 2004, although implementation of each change was slow. Plasmodium falciparum genetic polymorphisms are associated with alterations in drug sensitivity. We followed the prevalence of drug resistance-mediating P. falciparum polymorphisms in 982 samples from Tororo, a region of high transmission intensity, collected from three successive treatment trials conducted during 2003-2012, excluding samples with known recent prior treatment. Considering transporter mutations, prevalence of the mutant pfcrt 76T, pfmdr1 86Y, and pfmdr1 1246Y alleles decreased over time. Considering antifolate mutations, the prevalence of pfdhfr 51I, 59R, and 108N, and pfdhps 437G and 540E were consistently high; pfdhfr 164L and pfdhps 581G were uncommon, but most prevalent during 2008-2010. Our data suggest sequential selective pressures as different treatments were implemented, and they highlight the importance of genetic surveillance as treatment policies change over time. |
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