Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-18 (of 18 Records) |
Query Trace: Ade F[original query] |
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Lessons learned from the implementation of integrated serosurveillance of communicable diseases in the Americas
Saboyá-Díaz MI , Castellanos LG , Morice A , Ade MP , Rey-Benito G , Cooley GM , Scobie HM , Wiegand RE , Coughlin MM , Martin DL . Rev Panam Salud Publica 2023 47 e53 OBJECTIVE: Systematize the experience and identify challenges and lessons learned in the implementation of an initiative for integrated serosurveillance of communicable diseases using a multiplex bead assay in countries of the Americas. METHODS: Documents produced in the initiative were compiled and reviewed. These included concept notes, internal working papers, regional meetings reports, and survey protocols from the three participating countries (Mexico, Paraguay, and Brazil) and two additional countries (Guyana and Guatemala) where serology for several communicable diseases was included in neglected tropical diseases surveys. Information was extracted and summarized to describe the experience and the most relevant challenges and lessons learned. RESULTS: Implementing integrated serosurveys requires interprogrammatic and interdisciplinary work teams for the design of survey protocols to respond to key programmatic questions aligned to the needs of the countries. Valid laboratory results are critical and rely on the standardized installment and roll-out of laboratory techniques. Field teams require adequate training and supervision to properly implement survey procedures. The analysis and interpretation of serosurveys results should be antigen-specific, contextualizing the responses for each disease, and triangulated with programmatic and epidemiological data for making decisions tailored to specific population socioeconomic and ecologic contexts. CONCLUSIONS: Integrated serosurveillance as a complementary tool for functional epidemiological surveillance systems is feasible to use and key components should be considered: political engagement, technical engagement, and integrated planning. Aspects such as designing the protocol, selecting target populations and diseases, laboratory capacities, anticipating the capacities to analyze and interpret complex data, and how to use it are key. |
Portable Rabies Virus Sequencing in Canine Rabies Endemic Countries Using the Oxford Nanopore MinION.
Gigante CM , Yale G , Condori RE , Costa NC , Long NV , Minh PQ , Chuong VD , Tho ND , Thanh NT , Thin NX , Hanh NTH , Wambura G , Ade F , Mito O , Chuchu V , Muturi M , Mwatondo A , Hampson K , Thumbi SM , Thomae BG , de Paz VH , Meneses S , Munyua P , Moran D , Cadena L , Gibson A , Wallace RM , Pieracci EG , Li Y . Viruses 2020 12 (11) As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION's potential for low-cost, high volume sequencing of pathogens in locations with limited resources. |
Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance.
Mathieu LC , Cox H , Early AM , Mok S , Lazrek Y , Paquet JC , Ade MP , Lucchi NW , Grant Q , Udhayakumar V , Alexandre JS , Demar M , Ringwald P , Neafsey DE , Fidock DA , Musset L . Elife 2020 9 Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y. We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016-2017. Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance. In vitro growth competition assays revealed a fitness cost associated with these pfk13 variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America. These data place local malaria control efforts at risk in the Guiana Shield. | All recommended treatments against malaria include a drug called artemisinin or some of its derivatives. However, there are concerns that Plasmodium falciparum, the parasite that causes most cases of malaria, will eventually develop widespread resistance to the drug. A strain of P. falciparum partially resistant to artemisinin was seen in Cambodia in 2008, and it has since spread across Southeast Asia. The resistance appears to be frequently linked to a mutation known as pfk13 C580Y. Southeast Asia and Amazonia are considered to be hotspots for antimalarial drug resistance, and the pfk13 C580Y mutation was detected in the South American country of Guyana in 2010. To examine whether the mutation was still circulating in this part of the world, Mathieu et al. collected and analyzed 854 samples across Guyana between 2016 and 2017. Overall, 1.6% of the samples had the pfk13 C580Y mutation, but this number was as high as 8.8% in one region. Further analyses revealed that the mutation in Guyana had not spread from Southeast Asia, but that it had occurred in Amazonia independently. To better understand the impact of the pfk13 C580Y mutation, Mathieu et al. introduced this genetic change into non-resistant parasites from a country neighbouring Guyana. As expected, the mutation made P. falciparum highly resistant to artemisinin, but it also slowed the growth rate of the parasite. This disadvantage may explain why the mutation has not spread more rapidly through Guyana in recent years. Artemisinin and its derivatives are always associated with other antimalarial drugs to slow the development of resistance; there are concerns that reduced susceptibility to artemisinin leads to the parasites becoming resistant to the partner drugs. Further research is needed to evaluate how the pfk13 C580Y mutation affects the parasite's response to the typical combination of drugs that are given to patients. | eng |
WHO malaria nucleic acid amplification test external quality assessment scheme: results of distribution programmes one to three.
Cunningham JA , Thomson RM , Murphy SC , de la Paz Ade M , Ding XC , Incardona S , Legrand E , Lucchi NW , Menard D , Nsobya SL , Saez AC , Chiodini PL , Shrivastava J . Malar J 2020 19 (1) 129 BACKGROUND: The World Health Organization (WHO) recommends parasite-based diagnosis of malaria. In recent years, there has been surge in the use of various kinds of nucleic-acid amplification based tests (NAATs) for detection and identification of Plasmodium spp. to support clinical care in high-resource settings and clinical and epidemiological research worldwide. However, these tests are not without challenges, including lack (or limited use) of standards and lack of reproducibility, due in part to variation in protocols amongst laboratories. Therefore, there is a need for rigorous quality control, including a robust external quality assessment (EQA) scheme targeted towards malaria NAATs. To this effect, the WHO Global Malaria Programme worked with the UK National External Quality Assessment Scheme (UK NEQAS) Parasitology and with technical experts to launch a global NAAT EQA scheme in January 2017. METHODS: Panels of NAAT EQA specimens containing five major species of human-infecting Plasmodium at various parasite concentrations and negative samples were created in lyophilized blood (LB) and dried blood spot (DBS) formats. Two distributions per year were sent, containing five LB and five DBS specimens. Samples were tested and validated by six expert referee laboratories prior to distribution. Between 37 and 45 laboratories participated in each distribution and submitted results using the online submission portal of UK NEQAS. Participants were scored based on their laboratory's stated capacity to identify Plasmodium species, and individual laboratory reports were sent which included performance comparison with anonymized peers. RESULTS: Analysis of the first three distributions revealed that the factors that most significantly affected performance were sample format (DBS vs LB), species and parasite density, while laboratory location and the reported methodology used (type of nucleic acid extraction, amplification, or DNA vs RNA target) did not significantly affect performance. Referee laboratories performed better than non-referee laboratories. CONCLUSIONS: Globally, malaria NAAT assays now inform a range of clinical, epidemiological and research investigations. EQA schemes offer a way for laboratories to assess and improve their performance, which is critical to safeguarding the reliability of data and diagnoses especially in situations where various NAAT methodologies and protocols are in use. |
Artemether-Lumefantrine Efficacy for the Treatment of Uncomplicated Plasmodium falciparum Infection in Choco, Colombia after 8 Years as First-Line Treatment.
Olivera MJ , Guerra AP , Cortes LJ , Horth RZ , Padilla J , Novoa J , Ade MP , Ljolje D , Lucchi NW , Marquino W , Renteria M , Yurgaky W , Macedo de Oliveira A . Am J Trop Med Hyg 2020 102 (5) 1056-1063 Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum infection in Colombia. To assess AL efficacy for uncomplicated falciparum malaria in Quibdo, Choco, Colombia, we conducted a 28-day therapeutic efficacy study (TES) following the WHO guidelines. From July 2018 to February 2019, febrile patients aged 5-65 years with microscopy-confirmed P. falciparum mono-infection and asexual parasite density of 250-100,000 parasites/microL were enrolled and treated with a supervised 3-day course of AL. The primary endpoint was adequate clinical and parasitological response (ACPR) on day 28. We attempted to use polymerase chain reaction (PCR) genotyping to differentiate reinfection and recrudescence, and conducted genetic testing for antimalarial resistance-associated genes. Eighty-eight patients consented and were enrolled: four were lost to follow-up or missed treatment doses. Therefore, 84 (95.5%) participants reached a valid endpoint: treatment failure or ACPR. No patient remained microscopy positive for malaria on day 3, evidence of delayed parasite clearance and artemisinin resistance. One patient had recurrent infection (12 parasites/microL) on day 28. Uncorrected ACPR rate was 98.8% (83/84) (95% CI: 93.5-100%). The recurrent infection sample did not amplify during molecular testing, giving a PCR-corrected ACPR of 100% (83/83) (95% CI: 95.7-100%). No P. falciparum kelch 13 polymorphisms associated with artemisinin resistance were identified. Our results support high AL efficacy for falciparum malaria in Choco. Because of the time required to conduct TESs in low-endemic settings, it is important to consider complementary alternatives to monitor antimalarial efficacy and resistance. |
2016-2017 Arkansas mumps outbreak in a close-knit community: Assessment of the economic impact and response strategies
Pike J , Marin M , Guo A , Zhou F . Vaccine 2019 38 (6) 1481-1485 On August 8, 2016, a confirmed case of mumps was reported to the Arkansas Department of Health (ADH) in an adult resident of Springdale, Arkansas. By July 2017, nearly 3,000 cases of mumps were reported to ADH from 37 of the 75 counties in Arkansas. Over 50% of cases were in the Arkansas Marshallese community, a close-knit community characterized by large, and extended families sharing the same living space and communal activities. In a statewide effort, ADH collaborated with CDC, the Republic of the Marshall Island's (RMI) Ministry of Health, and the Arkansas Department of Education (ADE) to rapidly respond to and contain the outbreak. We assessed the economic burden to ADH of the outbreak response in terms of containment and vaccination costs, as well as response costs incurred by CDC, RMI, and ADE. The 2016-2017 Arkansas mumps outbreak was the second largest US mumps outbreak in over 30 years and was unique in size, spread, and population affected. Total public health response costs as a result of the outbreak were over $2.1 million, approximately $725 per case. The costs incurred to control this outbreak reflect the response strategies tailored to the affected populations, including consideration of social, cultural, and political factors in controlling transmission and requirements of distinctive strategies for public health outreach. Aside from the burden these outbreaks have on the affected population, we demonstrate the potential for high economic burden of these outbreaks to public health. |
Comparison of respiratory pathogen yields from Nasopharyngeal/Oropharyngeal swabs and sputum specimens collected from hospitalized adults in rural Western Kenya
Nyawanda BO , Njuguna HN , Onyango CO , Makokha C , Lidechi S , Fields B , Winchell JM , Katieno JS , Nyaundi J , Ade F , Emukule GO , Mott JA , Otieno N , Widdowson MA , Chaves SS . Sci Rep 2019 9 (1) 11237 Molecular diagnostic methods are becoming increasingly available for assessment of acute lower respiratory illnesses (ALRI). However, nasopharyngeal/oropharyngeal (NP/OP) swabs may not accurately reflect etiologic agents from the lower respiratory tract where sputum specimens are considered as a more representative sample. The pathogen yields from NP/OP against sputum specimens have not been extensively explored, especially in tropical countries. We compared pathogen yields from NP/OP swabs and sputum specimens from patients ≥18 years hospitalized with ALRI in rural Western Kenya. Specimens were tested for 30 pathogens using TaqMan Array Cards (TAC) and results compared using McNemar’s test. The agreement for pathogen detection between NP/OP and sputum specimens ranged between 85–100%. More viruses were detected from NP/OP specimens whereas Klebsiella pneumoniae and Mycobacterium tuberculosis were more common in sputum specimens. There was no clear advantage in using sputum over NP/OP specimens to detect pathogens of ALRI in adults using TAC in the context of this tropical setting. |
Successes and challenges of the One Health approach in Kenya over the last decade
Munyua PM , Njenga MK , Osoro EM , Onyango CO , Bitek AO , Mwatondo A , Muturi MK , Musee N , Bigogo G , Otiang E , Ade F , Lowther SA , Breiman RF , Neatherlin J , Montgomery J , Widdowson MA . BMC Public Health 2019 19 465 More than 75% of emerging infectious diseases are zoonotic in origin and a transdisciplinary, multi-sectoral One Health approach is a key strategy for their effective prevention and control. In 2004, US Centers for Disease Control and Prevention office in Kenya (CDC Kenya) established the Global Disease Detection Division of which one core component was to support, with other partners, the One Health approach to public health science. After catalytic events such as the global expansion of highly pathogenic H5N1 and the 2006 East African multi-country outbreaks of Rift Valley Fever, CDC Kenya supported key Kenya government institutions including the Ministry of Health and the Ministry of Agriculture, Livestock, and Fisheries to establish a framework for multi-sectoral collaboration at national and county level and a coordination office referred to as the Zoonotic Disease Unit (ZDU). The ZDU has provided Kenya with an institutional framework to highlight the public health importance of endemic and epidemic zoonoses including RVF, rabies, brucellosis, Middle East Respiratory Syndrome Coronavirus, anthrax and other emerging issues such as anti-microbial resistance through capacity building programs, surveillance, workforce development, research, coordinated investigation and outbreak response. This has led to improved outbreak response, and generated data (including discovery of new pathogens) that has informed disease control programs to reduce burden of and enhance preparedness for endemic and epidemic zoonotic diseases, thereby enhancing global health security. Since 2014, the Global Health Security Agenda implemented through CDC Kenya and other partners in the country has provided additional impetus to maintain this effort and Kenya's achievement now serves as a model for other countries in the region. Significant gaps remain in implementation of the One Health approach at subnational administrative levels; there are sustainability concerns, competing priorities and funding deficiencies. |
A Zika vaccine targeting NS1 protein protects immunocompetent adult mice in a lethal challenge model
Brault AC , Domi A , McDonald EM , Talmi-Frank D , McCurley N , Basu R , Robinson HL , Hellerstein M , Duggal NK , Bowen RA , Guirakhoo F . Sci Rep 2017 7 (1) 14769 Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Here, we describe the development of an alternative vaccine strategy encompassing the expression of ZIKV non-structural-1 (NS1) protein from a clinically proven safe, Modified Vaccinia Ankara (MVA) vector, thus averting the potential risk of ADE associated with structural protein-based ZIKV vaccines. A single intramuscular immunization of immunocompetent mice with the MVA-ZIKV-NS1 vaccine candidate provided robust humoral and cellular responses, and afforded 100% protection against a lethal intracerebral dose of ZIKV (strain MR766). This is the first report of (i) a ZIKV vaccine based on the NS1 protein and (ii) single dose protection against ZIKV using an immunocompetent lethal mouse challenge model. |
Giardiasis outbreak associated with asymptomatic food handlers in New York State, 2015
Figgatt M , Mergen K , Kimelstein D , Mahoney DM , Newman A , Nicholas D , Ricupero K , Cafiero T , Corry D , Ade J , Kurpiel P , Madison-Antenucci S , Anand M . J Food Prot 2017 80 (5) 837-841 Giardia duodenalis is a protozoan that causes a gastrointestinal illness called giardiasis. Giardiasis outbreaks in the United States are most commonly associated with waterborne transmission and are less commonly associated with food, person-to-person, and zoonotic transmission. During June to September 2015, an outbreak of 20 giardiasis cases occurred and were epidemiologically linked to a local grocery store chain on Long Island, New York. Further investigation revealed three asymptomatic food handlers were infected with G. duodenalis , and one food handler and one case were coinfected with Cryptosporidium spp. Although G. duodenalis was not detected in food samples, Cryptosporidium was identified in samples of spinach dip and potato salad. The G. duodenalis assemblage and subtype from one of the food handlers matched two outbreak cases for which genotyping could be performed. This outbreak highlights the potential role of asymptomatically infected food handlers in giardiasis outbreaks. |
Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles.
Ding XC , Ade MP , Baird JK , Cheng Q , Cunningham J , Dhorda M , Drakeley C , Felger I , Gamboa D , Harbers M , Herrera S , Lucchi N , Mayor A , Mueller I , Sattabongkot J , Ratsimbason A , Richards J , Tanner M , Gonzalez IJ . PLoS Negl Trop Dis 2017 11 (4) e0005516 The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for use the clinical management, control and elimination of P. vivax malaria. |
Isolation and characterization of a novel Rickettsia species (Rickettsia asembonensis sp. nov.) obtained from cat fleas (Ctenocephalides felis)
Maina AN , Luce-Fedrow A , Omulo S , Hang J , Chan TC , Ade F , Jima DD , Ogola E , Ge H , Breiman RF , Njenga MK , Richards AL . Int J Syst Evol Microbiol 2016 66 (11) 4512-4517 A novel rickettsial agent, 'Candidatus Rickettsia asembonensis' strain NMRCiiT, was isolated from cat fleas, Ctenocephalides felis, from Kenya. Genotypic characterization of the new isolate based on sequence analysis of five rickettsial genes, rrs, gltA, ompA, ompB and sca4, indicated that this isolate clustered with Rickettsia felis URRWXCal2. The degree of nucleotide similarity demonstrated that isolate NMRCiiT belongs within the genus Rickettsia and fulfils the criteria for classification as a representative of a novel species. The name Rickettsia asembonensis sp. nov. is proposed, with NMRCiiT (=DSM 100172T=CDC CRIRC RAS001T=ATCC VR-1827T) as the type strain. |
Generation of monoclonal antibodies against dengue virus type 4 and identification of enhancing epitopes on envelope protein
Tang CT , Liao MY , Chiu CY , Shen WF , Chiu CY , Cheng PC , Chang GJ , Wu HC . PLoS One 2015 10 (8) e0136328 The four serotypes of dengue virus (DENV1-4) pose a serious threat to global health. Cross-reactive and non-neutralizing antibodies enhance viral infection, thereby exacerbating the disease via antibody-dependent enhancement (ADE). Studying the epitopes targeted by these enhancing antibodies would improve the immune responses against DENV infection. In order to investigate the roles of antibodies in the pathogenesis of dengue, we generated a panel of 16 new monoclonal antibodies (mAbs) against DENV4. Using plaque reduction neutralization test (PRNT), we examined the neutralizing activity of these mAbs. Furthermore, we used the in vitro and in vivo ADE assay to evaluate the enhancement of DENV infection by mAbs. The results indicate that the cross-reactive and poorly neutralizing mAbs, DD11-4 and DD18-5, strongly enhance DENV1-4 infection of K562 cells and increase mortality in AG129 mice. The epitope residues of these enhancing mAbs were identified using virus-like particle (VLP) mutants. W212 and E26 are the epitope residues of DD11-4 and DD18-5, respectively. In conclusion, we generated and characterized 16 new mAbs against DENV4. DD11-4 and D18-5 possessed non-neutralizing activities and enhanced viral infection. Moreover, we identified the epitope residues of enhancing mAbs on envelope protein. These results may provide useful information for development of safe dengue vaccine. |
Strong association between human and animal Brucella seropositivity in a linked study in Kenya, 2012-2013
Osoro EM , Munyua P , Omulo S , Ogola E , Ade F , Mbatha P , Mbabu M , Nganga Z , Kairu S , Maritim M , Thumbi SM , Bitek A , Gaichugi S , Rubin C , Njenga K , Guerra M . Am J Trop Med Hyg 2015 93 (2) 224-231 Brucellosis is a common bacterial zoonotic infection but data on the prevalence among humans and animals is limited in Kenya. A cross-sectional survey was conducted in three counties practicing different livestock production systems to simultaneously assess the seroprevalence of, and risk factors for brucellosis among humans and their livestock (cattle, sheep, camels, and goats). A two-stage cluster sampling method with random selection of sublocations and households. Blood samples were collected from humans and animals and tested for Brucella immunoglobulin G (IgG) antibodies. Human and animal individual seroprevalence was 16% and 8%, respectively. Household and herd seroprevalence ranged from 5% to 73% and 6% to 68%, respectively. There was a 6-fold odds of human seropositivity in households with a seropositive animal compared with those without. Risk factors for human seropositivity included regular ingestion of raw milk (adjusted odds ratio [aOR] = 3.5, 95% confidence interval [CI] = 2.8-4.4), exposure to goats (herding, milking, and feeding) (aOR = 3.1, 95% CI = 2.5-3.8), and handling of animal hides (aOR = 1.8, 95% CI = 1.5-2.2). Attaining at least high school education and above was a protective factor for human seropositivity (aOR = 0.3, 95% CI = 0.3-0.4). This linked study provides evidence of a strong association between human and animal seropositivity at the household level. |
High prevalence of Rickettsia africae variants in Amblyomma variegatum ticks from domestic mammals in rural western Kenya: implications for human health
Maina AN , Jiang J , Omulo SA , Cutler SJ , Ade F , Ogola E , Feikin DR , Njenga MK , Cleaveland S , Mpoke S , Ng'ang'a Z , Breiman RF , Knobel DL , Richards AL . Vector Borne Zoonotic Dis 2014 14 (10) 693-702 Tick-borne spotted fever group (SFG) rickettsioses are emerging human diseases caused by obligate intracellular Gram-negative bacteria of the genus Rickettsia. Despite being important causes of systemic febrile illnesses in travelers returning from sub-Saharan Africa, little is known about the reservoir hosts of these pathogens. We conducted surveys for rickettsiae in domestic animals and ticks in a rural setting in western Kenya. Of the 100 serum specimens tested from each species of domestic ruminant 43% of goats, 23% of sheep, and 1% of cattle had immunoglobulin G (IgG) antibodies to the SFG rickettsiae. None of these sera were positive for IgG against typhus group rickettsiae. We detected Rickettsia africae-genotype DNA in 92.6% of adult Amblyomma variegatum ticks collected from domestic ruminants, but found no evidence of the pathogen in blood specimens from cattle, goats, or sheep. Sequencing of a subset of 21 rickettsia-positive ticks revealed R. africae variants in 95.2% (20/21) of ticks tested. Our findings show a high prevalence of R. africae variants in A. variegatum ticks in western Kenya, which may represent a low disease risk for humans. This may provide a possible explanation for the lack of African tick-bite fever cases among febrile patients in Kenya. |
Emergency department visits by adults for psychiatric medication adverse events
Hampton LM , Daubresse M , Chang HY , Alexander GC , Budnitz DS . JAMA Psychiatry 2014 71 (9) 1006-14 IMPORTANCE: In 2011, an estimated 26.8 million US adults used prescription medications for mental illness. OBJECTIVE: To estimate the numbers and rates of adverse drug event (ADE) emergency department (ED) visits involving psychiatric medications among US adults between January 1, 2009, and December 31, 2011. DESIGN AND SETTING: Descriptive analyses of active, nationally representative surveillance of ADE ED visits using the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance system and of drug prescribing during outpatient visits using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. PARTICIPANTS: Medical records from national probability samples of ED and outpatient visits by adults 19 years or older were reviewed and analyzed. EXPOSURES: Antidepressants, antipsychotics, lithium salts, sedatives and anxiolytics, and stimulants. MAIN OUTCOMES AND MEASURES: National estimates of ADE ED visits resulting from therapeutic psychiatric medication use and of psychiatric medication ADE ED visits per 10 000 outpatient visits at which psychiatric medications were prescribed. RESULTS: From 2009 through 2011, there were an estimated 89 094 (95% CI, 68 641-109 548) psychiatric medication ADE ED visits annually, with 19.3% (95% CI, 16.3%-22.2%) resulting in hospitalization and 49.4% (95% CI, 46.5%-52.4%) involving patients aged 19 to 44 years. Sedatives and anxiolytics, antidepressants, antipsychotics, lithium salts, and stimulants were implicated in an estimated 30 707 (95% CI, 23 406-38 008), 25 377 (95% CI, 19 051-31 704), 21 578 (95% CI, 16 599-26 557), 3620 (95% CI, 2311-4928), and 2779 (95% CI, 1764-3794) respective ADE ED visits annually. Antipsychotics and lithium salts were implicated in 11.7 (95% CI, 10.1-13.2) and 16.4 (95% CI, 13.0-19.9) ADE ED visits per 10 000 outpatient prescription visits, respectively, compared with 3.6 (95% CI, 3.2-4.1) for sedatives and anxiolytics, 2.9 (95% CI, 2.3-3.5) for stimulants, and 2.4 (95% CI, 2.1-2.7) for antidepressants. The commonly used sedative zolpidem tartrate was implicated in 11.5% (95% CI, 9.5%-13.4%) of all adult psychiatric medication ADE ED visits and in 21.0% (95% CI, 16.3%-25.7%) of visits involving adults 65 years or older, in both cases significantly more than any other psychiatric medication. CONCLUSIONS AND RELEVANCE: Psychiatric medications are implicated in many ADEs treated in US EDs. Efforts to reduce ADEs should include adults of all ages but might prioritize medications causing high numbers and rates of ED visits. |
Molecular determinants of dengue virus 2 envelope protein important for virus entry in Fc?RIIA-mediated antibody-dependent enhancement of infection.
Chotiwan N , Roehrig JT , Schlesinger JJ , Blair CD , Huang CYH . Virology 2014 456-457 (1) 238-246 Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fc receptors (FcR) on FcR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcRIIA, and binding of virus-Ab complexes with FcRIIA alone is not sufficient for ADE of infection. The FcRIIA mainly plays an auxiliary role in concentrating the virus-Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. |
Cough and cold medication adverse events after market withdrawal and labeling revision
Hampton LM , Nguyen DB , Edwards JR , Budnitz DS . Pediatrics 2013 132 (6) 1047-54 BACKGROUND: In October 2007, manufacturers voluntarily withdrew over-the-counter (OTC) infant cough and cold medications (CCMs) from the US market. A year later, manufacturers announced OTC CCM labeling would be revised to warn against OTC CCM use by children aged <4 years. We determined whether emergency department (ED) visits for CCM adverse drug events (ADEs) declined after these interventions. METHODS: We used National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance data from 2004 to 2011 to estimate the number of ED visits for CCM ADEs before and after each intervention. RESULTS: Among children aged <2 years, ED visits for CCM ADEs decreased from 4.1% of all ADE ED visits before the market withdrawal to 2.4% of all ADE visits afterward (difference in proportion: -1.7%, 95% confidence interval [CI]: -2.7% to -0.6%). Among children aged 2 to 3 years, ED visits for CCM ADEs decreased from 9.5% of all ADE ED visits before the labeling revision announcement to 6.5% of all ADE visits afterward (difference in proportion: -3.0%, 95% CI: -5.4% to -0.6%). Unsupervised ingestions accounted for 64.3% (95% CI: 51.1% to 77.5%) of CCM ADE ED visits involving children aged <2 years after the withdrawal and 88.8% (95% CI: 83.8% to 93.8%) of visits involving children aged 2 to 3 years after the labeling revision announcement. CONCLUSIONS: After a voluntary market withdrawal and labeling revision, ED visits for CCM ADEs declined among children aged <2 years and 2 to 3 years relative to ADE ED visits for all drugs. Interventions addressing unsupervised ingestions are needed to reduce CCM ADEs. |
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