Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-24 (of 24 Records) |
Query Trace: Parry R [original query] |
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Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Carey ME , Dyson ZA , Ingle DJ , Amir A , Aworh MK , Chattaway MA , Chew KL , Crump JA , Feasey NA , Howden BP , Keddy KH , Maes M , Parry CM , Van Puyvelde S , Webb HE , Afolayan AO , Alexander AP , Anandan S , Andrews JR , Ashton PM , Basnyat B , Bavdekar A , Bogoch II , Clemens JD , da Silva KE , De A , de Ligt J , Diaz Guevara PL , Dolecek C , Dutta S , Ehlers MM , Francois Watkins L , Garrett DO , Godbole G , Gordon MA , Greenhill AR , Griffin C , Gupta M , Hendriksen RS , Heyderman RS , Hooda Y , Hormazabal JC , Ikhimiukor OO , Iqbal J , Jacob JJ , Jenkins C , Jinka DR , John J , Kang G , Kanteh A , Kapil A , Karkey A , Kariuki S , Kingsley RA , Koshy RM , Lauer AC , Levine MM , Lingegowda RK , Luby SP , Mackenzie GA , Mashe T , Msefula C , Mutreja A , Nagaraj G , Nagaraj S , Nair S , Naseri TK , Nimarota-Brown S , Njamkepo E , Okeke IN , Perumal SPB , Pollard AJ , Pragasam AK , Qadri F , Qamar FN , Rahman SIA , Rambocus SD , Rasko DA , Ray P , Robins-Browne R , Rongsen-Chandola T , Rutanga JP , Saha SK , Saha S , Saigal K , Sajib MSI , Seidman JC , Shakya J , Shamanna V , Shastri J , Shrestha R , Sia S , Sikorski MJ , Singh A , Smith AM , Tagg KA , Tamrakar D , Tanmoy AM , Thomas M , Thomas MS , Thomsen R , Thomson NR , Tupua S , Vaidya K , Valcanis M , Veeraraghavan B , Weill FX , Wright J , Dougan G , Argimón S , Keane JA , Aanensen DM , Baker S , Holt KE . Elife 2023 12 BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng |
Bringing the clinical laboratory into the strategy to advance diagnostic excellence
Lubin IM , Astles JR , Shahangian S , Madison B , Parry R , Schmidt RL , Rubinstein ML . Diagnosis (Berl) 2021 8 (3) 281-294 OBJECTIVES: Clinical laboratory testing provides essential data for making medical diagnoses. Generating accurate and timely test results clearly communicated to the treating clinician, and ultimately the patient, is a critical component that supports diagnostic excellence. On the other hand, failure to achieve this can lead to diagnostic errors that manifest in missed, delayed and wrong diagnoses. CONTENT: Innovations that support diagnostic excellence address: 1) test utilization, 2) leveraging clinical and laboratory data, 3) promoting the use of credible information resources, 4) enhancing communication among laboratory professionals, health care providers and the patient, and 5) advancing the use of diagnostic management teams. Integrating evidence-based laboratory and patient-care quality management approaches may provide a strategy to support diagnostic excellence. Professional societies, government agencies, and healthcare systems are actively engaged in efforts to advance diagnostic excellence. Leveraging clinical laboratory capabilities within a healthcare system can measurably improve the diagnostic process and reduce diagnostic errors. SUMMARY: An expanded quality management approach that builds on existing processes and measures can promote diagnostic excellence and provide a pathway to transition innovative concepts to practice. OUTLOOK: There are increasing opportunities for clinical laboratory professionals and organizations to be part of a strategy to improve diagnoses. |
Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data
Barr DA , Lewis JM , Feasey N , Schutz C , Kerkhoff AD , Jacob ST , Andrews B , Kelly P , Lakhi S , Muchemwa L , Bacha HA , Hadad DJ , Bedell R , van Lettow M , Zachariah R , Crump JA , Alland D , Corbett EL , Gopinath K , Singh S , Griesel R , Maartens G , Mendelson M , Ward AM , Parry CM , Talbot EA , Munseri P , Dorman SE , Martinson N , Shah M , Cain K , Heilig CM , Varma JK , Gottberg AV , Sacks L , Wilson D , Squire SB , Lalloo DG , Davies G , Meintjes G . Lancet Infect Dis 2020 20 (6) 742-752 BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96.2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per muL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2.48, 95% CI 2.05-3.08) but not after 30 days (1.25, 0.84-2.49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3.15, 95% CI 1.16-8.84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A. |
The Severe Typhoid Fever in Africa Program: Study design and methodology to assess disease severity, host immunity, and carriage associated with invasive salmonellosis
Park SE , Toy T , Cruz Espinoza LM , Panzner U , Mogeni OD , Im J , Poudyal N , Pak GD , Seo H , Chon Y , Schutt-Gerowitt H , Mogasale V , Ramani E , Dey A , Park JY , Kim JH , Seo HJ , Jeon HJ , Haselbeck A , Conway Roy K , MacWright W , Adu-Sarkodie Y , Owusu-Dabo E , Osei I , Owusu M , Rakotozandrindrainy R , Soura AB , Kabore LP , Teferi M , Okeke IN , Kehinde A , Popoola O , Jacobs J , Lunguya Metila O , Meyer CG , Crump JA , Elias S , Maclennan CA , Parry CM , Baker S , Mintz ED , Breiman RF , Clemens JD , Marks F . Clin Infect Dis 2019 69 S422-s434 BACKGROUND: Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. METHODS: A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. RESULTS: Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. CONCLUSIONS: SETA supports public health policy on typhoid immunization strategy in Africa. |
Five months of voluntary wheel running downregulates skeletal muscle LINE-1 gene expression in rats.
Romero MA , Mumford PW , Roberson PA , Osburn SC , Parry HA , Kavazis AN , Gladden LB , Schwartz TS , Baker BA , Toedebusch RG , Childs TE , Booth FW , Roberts MD . Am J Physiol Cell Physiol 2019 317 (6) C1313-C1323 Transposable elements (TEs) are mobile DNA and constitute approximately half of the human genome. LINE-1 (L1) is the only active autonomous TE in the mammalian genome and has been implicated in a number of diseases as well as aging. We have previously reported skeletal muscle L1 expression is lower following acute and chronic exercise training in humans. Herein, we used a rodent model of voluntary wheel running to determine if long-term exercise training affects markers of skeletal muscle L1 regulation. Selectively-bred high running female Wistar rats (n=11 per group) were either given access to a running wheel (EX) or not (SED) at 5 weeks of age, and these conditions were maintained until 27 weeks of age. Thereafter, mixed gastrocnemius tissue was harvested and analyzed for L1 mRNA expression and DNA content along with other L1 regulation markers. We observed significantly (p<0.05) lower L1 mRNA expression, higher L1 DNA methylation, and less L1 DNA in accessible chromatin regions in EX versus SED rats. We followed these experiments with 3-h in vitro drug treatments in L6 myotubes to mimic transient exercise-specific signaling events. The AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR; 4mM) significantly decreased L1 mRNA expression in L6 myotubes. However, this effect was not facilitated through increased L1 DNA methylation. Collectively, these data suggest long-term voluntary wheel running downregulates skeletal muscle L1 mRNA, and this may occur through chromatin modifications. Enhanced AMPK signaling with repetitive exercise bouts may also decrease L1 mRNA expression, albeit the mechanism of action remains unknown. |
Circulation and characterization of seasonal influenza viruses in Cambodia, 2012-2015
Horwood PF , Karlsson EA , Horm SV , Ly S , Heng S , Chin S , Darapheak C , Saunders D , Chanthap L , Rith S , Y P , Chea KL , Sar B , Parry A , Ieng V , Tsuyouka R , Deng YM , Hurt AC , Barr IG , Komadina N , Buchy P , Dussart P . Influenza Other Respir Viruses 2019 13 (5) 465-476 BACKGROUND: Influenza virus circulation is monitored through the Cambodian influenza-like illness (ILI) sentinel surveillance system and isolates are characterized by the National Influenza Centre (NIC). Seasonal influenza circulation has previously been characterized by year-round activity and a peak during the rainy season (June-November). OBJECTIVES: We documented the circulation of seasonal influenza in Cambodia for 2012-2015 and investigated genetic, antigenic, and antiviral resistance characteristics of influenza isolates. PATIENTS/METHODS: Respiratory samples were collected from patients presenting with influenza-like illness (ILI) at 11 hospitals throughout Cambodia. First-line screening was conducted by the National Institute of Public Health and the Armed Forces Research Institute of Medical Sciences. Confirmation of testing and genetic, antigenic and antiviral resistance characterization was conducted by Institute Pasteur in Cambodia, the NIC. Additional virus characterization was conducted by the WHO Collaborating Centre for Reference and Research on Influenza (Melbourne, Australia). RESULTS: Between 2012 and 2015, 1,238 influenza-positive samples were submitted to the NIC. Influenza A(H3N2) (55.3%) was the dominant subtype, followed by influenza B (30.9%; predominantly B/Yamagata-lineage) and A(H1N1)pdm09 (13.9%). Circulation of influenza viruses began earlier in 2014 and 2015 than previously described, coincident with the emergence of A(H3N2) clades 3C.2a and 3C.3a, respectively. There was high diversity in the antigenicity of A(H3N2) viruses, and to a smaller extent influenza B viruses, during this period, with some mismatches with the northern and southern hemisphere vaccine formulations. All isolates tested were susceptible to the influenza antiviral drugs oseltamivir and zanamivir. CONCLUSIONS: Seasonal and year-round co-circulation of multiple influenza types/subtypes were detected in Cambodia during 2012-2015. |
Practical recommendations for the evaluation of improvement initiatives
Parry G , Coly A , Goldmann D , Rowe AK , Chattu V , Logiudice D , Rabrenovic M , Nambiar B . Int J Qual Health Care 2018 30 29-36 A lack of clear guidance for funders, evaluators and improvers on what to include in evaluation proposals can lead to evaluation designs that do not answer the questions stakeholders want to know. These evaluation designs may not match the iterative nature of improvement and may be imposed onto an initiative in a way that is impractical from the perspective of improvers and the communities with whom they work. Consequently, the results of evaluations are often controversial, and attribution remains poorly understood. Improvement initiatives are iterative, adaptive and context-specific. Evaluation approaches and designs must align with these features, specifically in their ability to consider complexity, to evolve as the initiative adapts over time and to understand the interaction with local context. Improvement initiatives often identify broadly defined change concepts and provide tools for care teams to tailor these in more detail to local conditions. Correspondingly, recommendations for evaluation are best provided as broad guidance, to be tailored to the specifics of the initiative. In this paper, we provide practical guidance and recommendations that funders and evaluators can use when developing an evaluation plan for improvement initiatives that seeks to: identify the questions stakeholders want to address; develop the initial program theory of the initiative; identify high-priority areas to measure progress over time; describe the context the initiative will be applied within; and identify experimental or observational designs that will address attribution. |
Immunohistochemistry and electrophysiological findings in swine abattoir workers with immune-mediated polyradiculoneuropathy
Muley SA , Holzbauer S , Clark B , Sejvar J , Lynfield R , Parry G , DeVries AS . J Neurol Sci 2018 385 34-38 Importance: Workers exposed to aerosolized brain in a swine-processing plant developed immune-mediated polyradiculoneuropathy (IP) possibly triggered by an immune response. Objective Immunohistochemistry results were correlated with electrophysiological variables to examine the immunopathogenesis of this disorder. Design/setting Laboratory studies used normal nerve tissue that was exposed to sera from 12 IP patients; 10 exposed controls; and 10 unexposed controls. Clinical and electrophysiological data from IP patients were obtained from medical record reviews. Main outcome measures Analysis included electromyography results of IP patients and nerve conduction studies examining CMAP amplitude, distal motor latency, motor conduction velocity, F-wave latency, sensory nerve action potential amplitude, and sensory nerve conduction velocity. Case and control results were compared relative to distance from exposure. Results Electrodiagnostic findings revealed prolongation of the distal and f-wave latencies suggestive of demyelination at the level of the nerve root and distal nerve terminals. Immunohistochemical results identified an antibody to the peripheral nerve, with staining at the level of the axolemma. Thus, IP may be a primary axonopathy with secondary paranodal demyelination causing the conduction changes. Staining of the distal and proximal portions of the nerve appears consistent with easier access through the blood-nerve barrier. Conclusions and relevance IP is an immune-mediated neuropathy related to antibodies to an axon-based antigen on peripheral nerves. Secondary paranodal demyelination is likely. Further studies to identify the primary axonal antigenic target would be useful. |
Establishing seasonal and alert influenza thresholds in Cambodia using the WHO method: implications for effective utilization of influenza surveillance in the tropics and subtropics
Ly S , Arashiro T , Ieng V , Tsuyuoka R , Parry A , Horwood P , Heng S , Hamid S , Vandemaele K , Chin S , Sar B , Arima Y . Western Pac Surveill Response J 2017 8 (1) 22-32 OBJECTIVE: To establish seasonal and alert thresholds and transmission intensity categories for influenza to provide timely triggers for preventive measures or upscaling control measures in Cambodia. METHODS: Using Cambodia's influenza-like illness (ILI) and laboratory-confirmed influenza surveillance data from 2009 to 2015, three parameters were assessed to monitor influenza activity: the proportion of ILI patients among all outpatients, proportion of ILI samples positive for influenza and the product of the two. With these parameters, four threshold levels (seasonal, moderate, high and alert) were established and transmission intensity was categorized based on a World Health Organization alignment method. Parameters were compared against their respective thresholds. RESULTS: Distinct seasonality was observed using the two parameters that incorporated laboratory data. Thresholds established using the composite parameter, combining syndromic and laboratory data, had the least number of false alarms in declaring season onset and were most useful in monitoring intensity. Unlike in temperate regions, the syndromic parameter was less useful in monitoring influenza activity or for setting thresholds. CONCLUSION: Influenza thresholds based on appropriate parameters have the potential to provide timely triggers for public health measures in a tropical country where monitoring and assessing influenza activity has been challenging. Based on these findings, the Ministry of Health plans to raise general awareness regarding influenza among the medical community and the general public. Our findings have important implications for countries in the tropics/subtropics and in resource-limited settings, and categorized transmission intensity can be used to assess severity of potential pandemic influenza as well as seasonal influenza. |
PEPFAR support of alcohol-HIV prevention activities in Namibia and Botswana: a framework for investigation, implementation and evaluation
Glenshaw M , Deluca N , Adams R , Parry C , Fritz K , Du Preez V , Voetsch K , Lekone P , Seth P , Bachanas P , Grillo M , Kresina TF , Pick B , Ryan C , Bock N . Glob Ment Health (Camb) 2016 3 e2 BACKGROUND: The association between harmful use of alcohol and HIV infection is well documented. To address this dual epidemic, the US President's Emergency Plan for AIDS Relief (PEPFAR) developed and implemented a multi-pronged approach primarily in Namibia and Botswana. We present the approach and preliminary results of the public health investigative and programmatic activities designed, initiated and supported by PEPFAR to combat the harmful use of alcohol and its association as a driver of HIV morbidity and mortality from 2008 to 2013. APPROACH: PEPFAR supported comprehensive alcohol programming using a matrix model approach that combined the socio-ecological framework and the Alcohol Misuse Prevention and Intervention Continuum. This structure enabled seven component objectives: (1) to quantify harmful use of alcohol through rapid assessments; (2) to develop and evaluate alcohol-based interventions; (3) to promote screening programs and alcohol abuse resource services; (4) to support stakeholder networks; (5) to support policy interventions and (6) structural interventions; and (7) to institutionalize universal prevention messages. DISCUSSION: Targeted PEPFAR support for alcohol activities resulted in several projects to address harmful alcohol use and HIV. Components are graphically conceptualized within the matrix model, demonstrating the intersections between primary, secondary and tertiary prevention activities and individual, interpersonal, community, and societal factors. Key initiative successes included leveraging alcohol harm prevention activities that enabled projects to be piloted in healthcare settings, schools, communities, and alcohol outlets. Primary challenges included the complexity of multi-sectorial programming, varying degrees of political will, and difficulties monitoring outcomes over the short duration of the program. |
Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.
Feasey NA , Hadfield J , Keddy KH , Dallman TJ , Jacobs J , Deng X , Wigley P , Barquist Barquist L , Langridge GC , Feltwell T , Harris SR , Mather AE , Fookes M , Aslett M , Msefula C , Kariuki S , Maclennan CA , Onsare RS , Weill FX , Le Hello S , Smith AM , McClelland M , Desai P , Parry CM , Cheesbrough J , French N , Campos J , Chabalgoity JA , Betancor L , Hopkins KL , Nair S , Humphrey TJ , Lunguya O , Cogan TA , Tapia MD , Sow SO , Tennant SM , Bornstein K , Levine MM , Lacharme-Lora L , Everett DB , Kingsley RA , Parkhill J , Heyderman RS , Dougan G , Gordon MA , Thomson NR . Nat Genet 2016 48 (10) 1211-1217 An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa. |
Virological response and antiretroviral drug resistance emerging during antiretroviral therapy at three treatment centers in Uganda
Kaleebu P , Kirungi W , Watera C , Asio J , Lyagoba F , Lutalo T , Kapaata AA , Nanyonga F , Parry CM , Magambo B , Nazziwa J , Nannyonjo M , Hughes P , Hladik W , Ruberantwari A , Namuwenge N , Musinguzi J , Downing R , Katongole-Mbidde E . PLoS One 2015 10 (12) e0145536 BACKGROUND: With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). METHODS: We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. RESULTS: Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36-7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/mul (AOR 2.80, 95% CI: 1.08-7.29) and viral load ≥100,000 copies/ml (AOR 2.48, 95% CI: 1.00-6.14). CONCLUSION: Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs. |
Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections
Crump JA , Sjolund-Karlsson M , Gordon MA , Parry CM . Clin Microbiol Rev 2015 28 (4) 901-37 Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015. |
Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.
Wong VK , Baker S , Pickard DJ , Parkhill J , Page AJ , Feasey NA , Kingsley RA , Thomson NR , Keane JA , Weill FX , Edwards DJ , Hawkey J , Harris SR , Mather AE , Cain AK , Hadfield J , Hart PJ , Thieu NT , Klemm EJ , Glinos DA , Breiman RF , Watson CH , Kariuki S , Gordon MA , Heyderman RS , Okoro C , Jacobs J , Lunguya O , Edmunds WJ , Msefula C , Chabalgoity JA , Kama M , Jenkins K , Dutta S , Marks F , Campos J , Thompson C , Obaro S , MacLennan CA , Dolecek C , Keddy KH , Smith AM , Parry CM , Karkey A , Mulholland EK , Campbell JI , Dongol S , Basnyat B , Dufour M , Bandaranayake D , Naseri TT , Singh SP , Hatta M , Newton P , Onsare RS , Isaia L , Dance D , Davong V , Thwaites G , Wijedoru L , Crump JA , De Pinna E , Nair S , Nilles EJ , Thanh DP , Turner P , Soeng S , Valcanis M , Powling J , Dimovski K , Hogg G , Farrar J , Holt KE , Dougan G . Nat Genet 2015 47 (6) 632-9 The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species. |
An action plan for translating cancer survivorship research into care.
Alfano CM , Smith T , de Moor JS , Glasgow RE , Khoury MJ , Hawkins NA , Stein KD , Rechis R , Parry C , Leach CR , Padgett L , Rowland JH . J Natl Cancer Inst 2014 106 (11) To meet the complex needs of a growing number of cancer survivors, it is essential to accelerate the translation of survivorship research into evidence-based interventions and, as appropriate, recommendations for care that may be implemented in a wide variety of settings. Current progress in translating research into care is stymied, with results of many studies un- or underutilized. To better understand this problem and identify strategies to encourage the translation of survivorship research findings into practice, four agencies (American Cancer Society, Centers for Disease Control and Prevention, LIVE STRONG: Foundation, National Cancer Institute) hosted a meeting in June, 2012, titled: "Biennial Cancer Survivorship Research Conference: Translating Science to Care." Meeting participants concluded that accelerating science into care will require a coordinated, collaborative effort by individuals from diverse settings, including researchers and clinicians, survivors and families, public health professionals, and policy makers. This commentary describes an approach stemming from that meeting to facilitate translating research into care by changing the process of conducting research-improving communication, collaboration, evaluation, and feedback through true and ongoing partnerships. We apply the T0-T4 translational process model to survivorship research and provide illustrations of its use. The resultant framework is intended to orient stakeholders to the role of their work in the translational process and facilitate the transdisciplinary collaboration needed to translate basic discoveries into best practices regarding clinical care, self-care/management, and community programs for cancer survivors. Finally, we discuss barriers to implementing translational survivorship science identified at the meeting, along with future directions to accelerate this process. |
Identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza A(H5N1) viruses detected in Cambodia in 2013.
Rith S , Davis CT , Duong V , Sar B , Horm SV , Chin S , Ly S , Laurent D , Richner B , Oboho I , Jang Y , Davis W , Thor S , Balish A , Iuliano AD , Sorn S , Holl D , Sok T , Seng H , Tarantola A , Tsuyuoka R , Parry A , Chea N , Allal L , Kitsutani P , Warren D , Prouty M , Horwood P , Widdowson MA , Lindstrom S , Villanueva J , Donis R , Cox N , Buchy P . J Virol 2014 88 (23) 13897-909 Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to absence of the mutations in poultry/environmental samples, suggested the mutations occurred during human infection and did not transmit further. |
Field study of dried blood spot specimens for HIV-1 drug resistance genotyping.
Parry CM , Parkin N , Diallo K , Mwebaza S , Batamwita R , DeVos J , Bbosa N , Lyagoba F , Magambo B , Jordan MR , Downing R , Zhang G , Kaleebu P , Yang C , Bertagnolio S . J Clin Microbiol 2014 52 (8) 2868-75 Dried blood spots (DBS) are an alternative specimen type for HIV drug resistance genotyping in resource-limited settings. Data relating to the impact of DBS storage and shipment conditions on genotyping efficiency under field conditions are limited. We compared genotyping efficiency and resistance profiles of DBS stored and shipped at different temperatures to plasma specimens collected in parallel from patients receiving antiretroviral therapy in Uganda. Plasma and four DBS cards from anti-coagulated venous blood, and a 5th card from finger-prick blood were prepared from 103 HIV-patients with a median VL of 56,795 copies/ml (range 1,081 - 2,964,191). DBS were stored at ambient temperature for 2 or 4 weeks or frozen at -80 degrees C, and shipped from Uganda to the United States, at ambient temperature or frozen on dry ice, for genotyping using a broadly sensitive in-house method. Plasma (97.1%) and DBS (98.1%) stored and shipped frozen had similar genotyping efficiency. DBS stored frozen (97.1%) or at ambient temperature for 2 weeks (93.2%) and shipped at ambient temperature also had similar genotyping efficiency. Genotyping efficiency was reduced for DBS stored at ambient temperature for 4 weeks (89.3%, P=0.03) or prepared from finger-prick blood and stored at ambient temperature for 2 weeks (77.7%, P<0.001) compared to DBS prepared from venous blood and handled similarly. Resistance profiles were similar between plasma and DBS specimens. This study delineates the optimal DBS collection, storage and shipping conditions and opens a new avenue for cost-saving ambient temperature DBS specimen shipments for HIVDR surveillances in resource-limited settings. |
A prospective study of the causes of febrile illness requiring hospitalization in children in Cambodia
Chheng K , Carter MJ , Emary K , Chanpheaktra N , Moore CE , Stoesser N , Putchhat H , Sona S , Reaksmey S , Kitsutani P , Sar B , van Doorn HR , Uyen NH , Van Tan L , Paris D , Blacksell SD , Amornchai P , Wuthiekanun V , Parry CM , Day NP , Kumar V . PLoS One 2013 8 (4) e60634 BACKGROUND: Febrile illnesses are pre-eminent contributors to morbidity and mortality among children in South-East Asia but the causes are poorly understood. We determined the causes of fever in children hospitalised in Siem Reap province, Cambodia. METHODS AND FINDINGS: A one-year prospective study of febrile children admitted to Angkor Hospital for Children, Siem Reap. Demographic, clinical, laboratory and outcome data were comprehensively analysed. Between October 12(th) 2009 and October 12(th) 2010 there were 1225 episodes of febrile illness in 1180 children. Median (IQR) age was 2.0 (0.8-6.4) years, with 850 (69%) episodes in children <5 years. Common microbiological diagnoses were dengue virus (16.2%), scrub typhus (7.8%), and Japanese encephalitis virus (5.8%). 76 (6.3%) episodes had culture-proven bloodstream infection, including Salmonella enterica serovar Typhi (22 isolates, 1.8%), Streptococcus pneumoniae (13, 1.1%), Escherichia coli (8, 0.7%), Haemophilus influenzae (7, 0.6%), Staphylococcus aureus (6, 0.5%) and Burkholderia pseudomallei (6, 0.5%). There were 69 deaths (5.6%), including those due to clinically diagnosed pneumonia (19), dengue virus (5), and melioidosis (4). 10 of 69 (14.5%) deaths were associated with culture-proven bloodstream infection in logistic regression analyses (odds ratio for mortality 3.4, 95% CI 1.6-6.9). Antimicrobial resistance was prevalent, particularly in S. enterica Typhi, (where 90% of isolates were resistant to ciprofloxacin, and 86% were multi-drug resistant). Comorbid undernutrition was present in 44% of episodes and a major risk factor for acute mortality (OR 2.1, 95% CI 1.1-4.2), as were HIV infection and cardiac disease. CONCLUSION: We identified a microbiological cause of fever in almost 50% of episodes in this large study of community-acquired febrile illness in hospitalized children in Cambodia. The range of pathogens, antimicrobial susceptibility, and co-morbidities associated with mortality described will be of use in the development of rational guidelines for infectious disease treatment and control in Cambodia and South-East Asia. |
A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010
Lim Stephen S , Vos Theo , Flaxman Abraham D , Danaei Goodarz , Shibuya Kenji , Adair-Rohani Heather , Amann Markus , Anderson H Ross , Andrews Kathryn G , Aryee Martin , Atkinson Charles , Bacchus Loraine J , Bahalim Adil N , Balakrishnan Kalpana , Balmes John , Barker-Collo Suzanne , Baxter Amanda , Bell Michelle L , Blore Jed D , Blyth Fiona , Bonner Carissa , Borges Guilherme , Bourne Rupert , Boussinesq Michel , Brauer Michael , Brooks Peter , Bruce Nigel G , Brunekreef Bert , Bryan-Hancock Claire , Bucello Chiara , Buchbinder Rachelle , Bull Fiona , Burnett Richard T , Byers Tim E , Calabria Bianca , Carapetis Jonathan , Carnahan Emily , Chafe Zoe , Charlson Fiona , Chen Honglei , Chen Jian Shen , Cheng Andrew Tai-Ann , Child Jennifer Christine , Cohen Aaron , Colson K Ellicott , Cowie Benjamin C , Darby Sarah , Darling Susan , Davis Adrian , Degenhardt Louisa , Dentener Frank , Des Jarlais Don C , Devries Karen , Dherani Mukesh , Ding Eric L , Dorsey E Ray , Driscoll Tim , Edmond Karen , Ali Suad Eltahir , Engell Rebecca E , Erwin Patricia J , Fahimi Saman , Falder Gail , Farzadfar Farshad , Ferrari Alize , Finucane Mariel M , Flaxman Seth , Fowkes Francis Gerry R , Freedman Greg , Freeman Michael K , Gakidou Emmanuela , Ghosh Santu , Giovannucci Edward , Gmel Gerhard , Graham Kathryn , Grainger Rebecca , Grant Bridget , Gunnell David , Gutierrez Hialy R , Hall Wayne , Hoek Hans W , Hogan Anthony , Hosgood H Dean 3rd , Hoy Damian , Hu Howard , Hubbell Bryan J , Hutchings Sally J , Ibeanusi Sydney E , Jacklyn Gemma L , Jasrasaria Rashmi , Jonas Jost B , Kan Haidong , Kanis John A , Kassebaum Nicholas , Kawakami Norito , Khang Young-Ho , Khatibzadeh Shahab , Khoo Jon-Paul , Kok Cindy , Laden Francine , Lalloo Ratilal , Lan Qing , Lathlean Tim , Leasher Janet L , Leigh James , Li Yang , Lin John Kent , Lipshultz Steven E , London Stephanie , Lozano Rafael , Lu Yuan , Mak Joelle , Malekzadeh Reza , Mallinger Leslie , Marcenes Wagner , March Lyn , Marks Robin , Martin Randall , McGale Paul , McGrath John , Mehta Sumi , Mensah George A , Merriman Tony R , Micha Renata , Michaud Catherine , Mishra Vinod , Hanafiah Khayriyyah Mohd , Mokdad Ali A , Morawska Lidia , Mozaffarian Dariush , Murphy Tasha , Naghavi Mohsen , Neal Bruce , Nelson Paul K , Nolla Joan Miquel , Norman Rosana , Olives Casey , Omer Saad B , Orchard Jessica , Osborne Richard , Ostro Bart , Page Andrew , Pandey Kiran D , Parry Charles D H , Passmore Erin , Patra Jayadeep , Pearce Neil , Pelizzari Pamela M , Petzold Max , Phillips Michael R , Pope Dan , Pope C Arden 3rd , Powles John , Rao Mayuree , Razavi Homie , Rehfuess Eva A , Rehm Jurgen T , Ritz Beate , Rivara Frederick P , Roberts Thomas , Robinson Carolyn , Rodriguez-Portales Jose A , Romieu Isabelle , Room Robin , Rosenfeld Lisa C , Roy Ananya , Rushton Lesley , Salomon Joshua A , Sampson Uchechukwu , Sanchez-Riera Lidia , Sanman Ella , Sapkota Amir , Seedat Soraya , Shi Peilin , Shield Kevin , Shivakoti Rupak , Singh Gitanjali M , Sleet David A , Smith Emma , Smith Kirk R , Stapelberg Nicolas J C , Steenland Kyle , Stockl Heidi , Stovner Lars Jacob , Straif Kurt , Straney Lahn , Thurston George D , Tran Jimmy H , Van Dingenen Rita , van Donkelaar Aaron , Veerman J Lennert , Vijayakumar Lakshmi , Weintraub Robert , Weissman Myrna M , White Richard A , Whiteford Harvey , Wiersma Steven T , Wilkinson James D , Williams Hywel C , Williams Warwick , Wilson Nicholas , Woolf Anthony D , Yip Paul , Zielinski Jan M , Lopez Alan D , Murray Christopher J L , Ezzati Majid , Global Burden of Disease Study 2010 . Lancet 2013 380 (9859) 2224-60 BACKGROUND: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS: In 2010, the three leading risk factors for global disease burden were high blood pressure (7.0% [95% uncertainty interval 6.2-7.7] of global DALYs), tobacco smoking including second-hand smoke (6.3% [5.5-7.0]), and alcohol use (5.5% [5.0-5.9]). In 1990, the leading risks were childhood underweight (7.9% [6.8-9.4]), household air pollution from solid fuels (HAP; 7.0% [5.6-8.3]), and tobacco smoking including second-hand smoke (6.1% [5.4-6.8]). Dietary risk factors and physical inactivity collectively accounted for 10.0% (95% UI 9.2-10.8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0.9% (0.4-1.6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. FUNDING: Bill & Melinda Gates Foundation. |
The effect of sample handling on cross sectional HIV incidence testing results
Laeyendecker O , Latimore A , Eshleman SH , Summerton J , Oliver AE , Gamiel J , Dobbs T , Mei J , Murphy G , Parry JV , Owen SM , Quinn TC . PLoS One 2011 6 (10) e25899 OBJECTIVE(S): To determine if mishandling prior to testing would make a sample from a chronically infected subject appear recently infected when tested by cross-sectional HIV incidence assays. METHODS: Serum samples from 31 subjects with chronic HIV infection were tested. Samples were subjected to different handling conditions, including incubation at 4 degrees C, 25 degrees C and 37 degrees C, for 1, 3, 7 or 15 days prior to testing. Samples were also subjected to 1,3, 7 and 15 freeze-thaw cycles prior to testing. Samples were tested using the BED capture enzyme immuno assay (BED-CEIA), Vironostika-less sensitive (V-LS), and an avidity assay using the Genetic Systems HIV-1/HIV-2 plus O EIA (avidity assay). RESULTS: Compared to the sample that was not subjected to any mishandling conditions, for the BED-CEIA, V-LS and avidity assay, there was no significant change in test results for samples incubated at 4 degrees C or 25 degrees C prior to testing. No impact on test results occurred after 15 freeze-thaw cycles. A decrease in assay results was observed when samples were held for 3 days or longer at 37 degrees C prior to testing. CONCLUSIONS: Samples can be subjected up to 15 freeze-thaw cycles without affecting the results the BED-CEIA, Vironostika-LS, or avidity assays. Storing samples at 4 degrees C or 25 degrees C for up to fifteen days prior to testing had no impact on test results. However, storing samples at 37 degrees C for three or more days did affect results obtained with these assays. |
Increased detection of the HIV-1 reverse transcriptase M184V mutation using mutation-specific minority assays in a UK surveillance study suggests evidence of unrecognized transmitted drug resistance
Buckton A , Prabhu D , Motamed C , Harris R , Hill C , Murphy G , Parry J , Johnson J , Lowndes C , Gill N , Pillay D , Cane P . HIV Med 2011 12 (4) 250-4 OBJECTIVES: The aim of the study was to estimate the levels of transmitted drug resistance (TDR) in HIV-1 using very sensitive assays to detect minority drug-resistant populations. METHODS: We tested unlinked anonymous serum specimens from sexual health clinic attendees, who had not received an HIV diagnosis at the time of sampling, by both standard genotyping and using minority detection assays. RESULTS: By standard genotyping, 21 of 165 specimens (12.7%) showed evidence of drug resistance, while, using a combination of standard genotyping and minority mutation assays targeting three commonly observed drug resistance mutations which cause high-level resistance to commonly prescribed first-line antiretroviral therapy (ART), this rose to 32 of 165 (19.4%). This increase of 45% in drug resistance levels [95% confidence interval (CI) 15.2-83.7%; P=0.002] was statistically significant. Almost all of this increase was accounted for by additional detections of the M184V mutation. CONCLUSIONS: Future surveillance studies of TDR in the United Kingdom should consider combining standard genotyping and minority-specific assays to provide more accurate estimates, particularly when using specimens collected from chronic HIV infections in which TDR variants may have declined to low levels. |
Rapid pneumococcal evolution in response to clinical interventions
Croucher NJ , Harris SR , Fraser C , Quail MA , Burton J , van der Linden M , McGee L , von Gottberg A , Song JH , Ko KS , Pichon B , Baker S , Parry CM , Lambertsen LM , Shahinas D , Pillai DR , Mitchell TJ , Dougan G , Tomasz A , Klugman KP , Parkhill J , Hanage WP , Bentley SD . Science 2011 331 (6016) 430-4 Epidemiological studies of the naturally transformable bacterial pathogen Streptococcus pneumoniae have previously been confounded by high rates of recombination. Sequencing 240 isolates of the PMEN1 (Spain(23F)-1) multidrug-resistant lineage enabled base substitutions to be distinguished from polymorphisms arising through horizontal sequence transfer. More than 700 recombinations were detected, with genes encoding major antigens frequently affected. Among these were 10 capsule-switching events, one of which accompanied a population shift as vaccine-escape serotype 19A isolates emerged in the USA after the introduction of the conjugate polysaccharide vaccine. The evolution of resistance to fluoroquinolones, rifampicin, and macrolides was observed to occur on multiple occasions. This study details how genomic plasticity within lineages of recombinogenic bacteria can permit adaptation to clinical interventions over remarkably short time scales. |
Quantification of monofluoroacetate and monochloroacetate in human urine by isotope dilution liquid chromatography tandem mass spectrometry
Hamelin EI , Mawhinney DB , Parry R , Kobelski RJ . J Chromatogr B Analyt Technol Biomed Life Sci 2010 878 1045-50 The rodenticide monofluoroacetate (MFA) and monochloroacetate (MCA), a chemical intermediate from several chemical syntheses, have been identified as potential agents of chemical terrorism due to their high toxicity. In preparation for response to poisonings and mass exposures, we have developed a quantification method using isotopic dilution to determine MFA and MCA in urine from 50 to 5000 ng/mL. Both analytes were extracted from urine using solid-phase extraction; extraction recoveries were 62% (MFA) and 76% (MCA). The extracts were then separated with isocratic high-performance liquid chromatography and identified using electrospray ionization tandem mass spectrometry, with detection limits of 0.9 and 7.0 ng/mL for MFA and MCA, respectively. Selectivity was established for both analytes with unique chromatographic retention times which were correlated with isotopically labeled internal standards and the use of two mass spectral transitions for each compound. The intra-day variability was less than 5% for both analytes and the inter-day variability was 7% for MFA and 6% for MCA. |
Rapid assessment of HIV risk behavior in drug using sex workers in three cities in South Africa
Parry CD , Dewing S , Petersen P , Carney T , Needle R , Kroeger K , Treger L . AIDS Behav 2009 13 (5) 849-59 A rapid assessment was undertaken with drug using commercial sex workers (CSWs) to investigate practices putting them at risk for contracting HIV. It included key informant (KI) (N = 67) and focus group (N = 10) interviews in locations with a high prevalence of drug use in Cape Town, Durban and Pretoria, South Africa. HIV testing of KIs was conducted. Cocaine, Ecstasy, heroin and methaqualone are used by CSWs prior to, during and after sex. Drugs enhance the sexual experience and prolong sex sessions. Interviews revealed inconsistent condom use among CSWs together with other risky sexual practices such as needle sharing. Among CSWs who agreed to HIV testing, 34% tested positive. Barriers to accessing drug treatment and HIV treatment and preventive services were identified. Interventions recognizing the role of drug abuse in HIV transmission should be prioritized, and issues of access to services, stigma and power relations must be considered. |
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