Publications
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Cuomo-Dannenburg GM, Walker P, Verity R, et al., 2019, IMPLICATION OF SULFADOXINE-PYRIMETHAMINE RESISTANCE-ASSOCIATED MUTATIONS ON THE PROTECTIVE EFFICACY OF SEASONAL MALARIA CHEMOPREVENTION: A PHARMACOKINETIC-PHARMACODYNAMIC ANALYSIS, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 189-189, ISSN: 0002-9637
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Brazeau NF, Mitchell C, Deutsch-Feldman M, et al., 2019, THE EPIDEMIOLOGY OF <i>PLASMODIUM VIVAX</i> AMONG ADULTS IN THE DEMOCRATIC REPUBLIC OF THE CONGO, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 209-209, ISSN: 0002-9637
Verity R, Aydemir O, Brazeau NF, et al., 2019, SPATIAL-GENETIC ANALYSIS OF <i>PLASMODIUM FALCIPARUM</i> IN THE DEMOCRATIC REPUBLIC OF THE CONGO THROUGH MOLECULAR INVERSION PROBES, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 597-597, ISSN: 0002-9637
Wesolowski A, Taylor AR, Chang H-H, et al., 2018, Mapping malaria by combining parasite genomic and epidemiologic data, BMC Medicine, Vol: 16
Hogan A, Winskill P, Verity R, et al., 2018, Informing target product profiles for a second-generation childhood malaria vaccine: a modelling study, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 583-583, ISSN: 0002-9637
Okell L, Reiter LM, Ebbe LS, et al., 2018, Emerging implications of policies on malaria treatment: genetic changes in the Pfmdr-1 gene affecting susceptibility to artemether-lumefantrine and artesunate-amodiaquine in Africa, BMJ Global Health, Vol: 3, ISSN: 2059-7908
Artemether–lumefantrine (AL) and artesunate–amodiaquine (AS-AQ) are the most commonly used artemisinin-based combination therapies (ACT) for treatment of Plasmodium falciparum in Africa. Both treatments remain efficacious, but single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multidrug resistance 1 (Pfmdr1) gene may compromise sensitivity. AL and AS-AQ exert opposing selective pressures: parasites with genotype 86Y, Y184 and 1246Y are partially resistant to AS-AQ treatment, while N86, 184 F and D1246 are favoured by AL treatment. Through a systematic review, we identified 397 surveys measuring the prevalence of Pfmdr1 polymorphisms at positions 86 184 or 1246 in 30 countries in Africa. Temporal trends in SNP frequencies after introduction of AL or AS-AQ as first-line treatment were analysed in 32 locations, and selection coefficients estimated. We examined associations between antimalarial policies, consumption, transmission intensity and rate of SNP selection. 1246Y frequency decreased on average more rapidly in locations where national policy recommended AL (median selection coefficient(s) of −0.083), compared with policies of AS-AQ or both AL and AS-AQ (median s=−0.035 and 0.021, p<0.001 respectively). 86Y frequency declined markedly after ACT policy introduction, with a borderline significant trend for a more rapid decline in countries with AL policies (p=0.055). However, these trends could also be explained by a difference in initial SNP frequencies at the time of ACT introduction. There were non-significant trends for faster selection of N86 and D1246 in areas with higher AL consumption and no trend with transmission intensity. Recorded consumption of AS-AQ was low in the locations and times Pfmdr1 data were collected. SNP trends in countries with AL policies suggest a broad increase in sensitivity of parasites to AS-AQ, by 7–10 years after AL introduction. Observed rates of selection have implications for pla
Aydemir O, Janko M, Hathaway NJ, et al., 2018, Drug-resistance and population structure of plasmodium falciparum across the Democratic Republic of Congo using high-throughput molecular inversion probes, Journal of Infectious Diseases, Vol: 218, Pages: 946-955, ISSN: 0022-1899
A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013–2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ongoing spread of double and triple mutants compared with 2007. These findings suggest that parasites in the DRC remain panmictic despite rapidly spreading antimalarial-resistance mutations. Moreover, highly multiplexed targeted sequencing using MIPs emerges as a cost-effective method for elucidating pathogen genetics in complex infections in large cohorts.
Hogan AB, Winskill P, Verity R, et al., 2018, Modelling population-level impact to inform target product profiles for childhood malaria vaccines, BMC Medicine, Vol: 16, ISSN: 1741-7015
BackgroundThe RTS,S/AS01 vaccine for Plasmodium falciparum malaria demonstrated moderate efficacy in 5–17-month-old children in phase 3 trials, and from 2018, the vaccine will be evaluated through a large-scale pilot implementation program. Work is ongoing to optimise this vaccine, with higher efficacy for a different schedule demonstrated in a phase 2a challenge study. The objective of our study was to investigate the population-level impact of a modified RTS,S/AS01 schedule and dose amount in order to inform the target product profile for a second-generation malaria vaccine.MethodsWe used a mathematical modelling approach as the basis for our study. We simulated the changing anti-circumsporozoite antibody titre following vaccination and related the titre to vaccine efficacy. We then implemented this efficacy profile within an individual-based model of malaria transmission. We compared initial efficacy, duration and dose timing, and evaluated the potential public health impact of a modified vaccine in children aged 5–17 months, measuring clinical cases averted in children younger than 5 years.ResultsIn the first decade of delivery, initial efficacy was associated with a higher reduction in childhood clinical cases compared to vaccine duration. This effect was more pronounced in high transmission settings and was due to the efficacy benefit occurring in younger ages where disease burden is highest. However, the low initial efficacy and long duration schedule averted more cases across all age cohorts if a longer time horizon was considered. We observed an age-shifting effect due to the changing immunological profile in higher transmission settings, in scenarios where initial efficacy was higher, and the fourth dose administered earlier.ConclusionsOur findings indicate that, for an imperfect childhood malaria vaccine with suboptimal efficacy, it may be advantageous to prioritise initial efficacy over duration. We predict that a modified vaccine could outpe
O'Reilly KM, Grassly N, Verity R, 2018, Population sensitivity of acute flaccid paralysis and environmental surveillance for serotype 1 poliovirus in Pakistan: an observational study, BMC Infectious Diseases, Vol: 18, ISSN: 1471-2334
BackgroundTo support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation.MethodsData for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surveillance source and parameters such as the duration of infection within a community.ResultsThe location and timing of poliomyelitis cases showed spatial and temporal variability. The sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a district and its neighbours per month was on average 30.0% (95% CI 24.8–35.8) and increased with the incidence of poliomyelitis cases. The average population sensitivity of a single environmental sample was 59.4% (95% CI 55.4–63.0), with significant variation in site-specific estimates (median varied from 33.3–79.2%). The combined population sensitivity of environmental and AFP surveillance in a given month was on average 98.1% (95% CI 97.2–98.7), assuming four samples per month for each site.ConclusionsES can be a highly sensitive supplement to AFP surveillance in areas with converging sewage systems. As ES for poliovirus is expanded, it will be important to identify factors associated with variation in site sensitivity, leading to improved site selection and surveillance system performance.
Verity RJ, Hathaway N, Waltmann A, et al., 2018, Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of the Congo, Malaria Journal, Vol: 17, ISSN: 1475-2875
Background: The Democratic Republic of the Congo (DRC) bears a high burden of malaria, which is exacerbated inpregnant women. The VAR2CSA protein plays a crucial role in pregnancy-associated malaria (PAM), and hence quantifyingdiversity at the var2csa locus in the DRC is important in understanding the basic epidemiology of PAM, and indeveloping a robust vaccine against PAM.Methods: Samples were taken from the 2013–14 Demographic and Health Survey conducted in the DRC, focusingon children under 5 years of age. A short subregion of the var2csa gene was sequenced in 115 spatial clusters, givingcountry-wide estimates of sequence polymorphism and spatial population structure.Results: Results indicate that var2csa is highly polymorphic, and that diversity is being maintained through balancingselection, however, there is no clear signal of phylogenetic or geographic structure to this diversity. Linear modellingdemonstrates that the number of var2csa variants in a cluster correlates directly with cluster prevalence, but not withother epidemiological factors such as urbanicity.Conclusions: Results suggest that the DRC fts within the global pattern of high var2csa diversity and little geneticdiferentiation between regions. A broad multivalent VAR2CSA vaccine candidate could beneft from targeting stableregions and common variants to address the substantial genetic diversity.
Deutsch-Feldman M, Aydemir O, Carrel M, et al., 2018, SPATIAL EPIDEMIOLOGY OF <it>PLASMODIUM FALCIPARUM</it> DRUG RESISTANCE IN THE DEMOCRATIC REPUBLIC OF CONGO, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 321-321, ISSN: 0002-9637
Watson O, Verity R, Ghani A, et al., 2018, THE IMPACT OF SEASONAL VARIATION IN THE DETECTION OF CLINICALLY RELEVANT <it>PLASMODIUM FALCIPARUM HRP2</it> GENE DELETIONS: A MODELLING STUDY, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 340-340, ISSN: 0002-9637
Parr JB, Verity R, Doctor S, et al., 2017, EVOLUTION AND SPREAD OF "STEALTH" <i>PFHRP2</i> DELETIONS IN <i>PLASMODIUM FALCIPARUM</i> IN THE DEMOCRATIC REPUBLIC OF THE CONGO, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 85-85, ISSN: 0002-9637
Watson O, Slater HC, Verity R, et al., 2017, Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa, eLife, Vol: 6, ISSN: 2050-084X
Rapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent P. falciparum RDTs detect histidine-rich protein 2 (PfHRP2). However, pfhrp2 gene deletions yielding false-negative RDTs, first reported in South America in 2010, have been confirmed in Africa and Asia. We developed a mathematical model to explore the potential for RDT-led diagnosis to drive selection of pfhrp2-deleted parasites. Low malaria prevalence and high frequencies of people seeking treatment resulted in the greatest selection pressure. Calibrating our model against confirmed pfhrp2-deletions in the Democratic Republic of Congo, we estimate a starting frequency of 6% pfhrp2-deletion prior to RDT introduction. Furthermore, the patterns observed necessitate a degree of selection driven by the introduction of PfHRP2-based RDT-guided treatment. Combining this with parasite prevalence and treatment coverage estimates, we map the model-predicted spread of pfhrp2-deletion, and identify the geographic regions in which surveillance for pfhrp2-deletion should be prioritised.
Lotterhos KE, Card DC, Schaal SM, et al., 2017, Composite measures of selection can improve the signal-to-noise ratio in genome scans, METHODS IN ECOLOGY AND EVOLUTION, Vol: 8, Pages: 717-727, ISSN: 2041-210X
Papini A, Kim Rossmo D, Le Comber SC, et al., 2017, The use of jackknifing for the evaluation of geographic profiling reliability, Ecological Informatics, Vol: 38, Pages: 76-81, ISSN: 1574-9541
Verity R, Collins C, Card DC, et al., 2017, MINOTAUR: A platform for the analysis and visualization of multivariate results from genome scans with R Shiny, MOLECULAR ECOLOGY RESOURCES, Vol: 17, Pages: 33-43, ISSN: 1755-098X
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- Citations: 34
Faulkner SC, Verity R, Roberts D, et al., 2017, Using geographic profiling to compare the value of sightings vs trap data in a biological invasion, Diversity and Distributions, Vol: 23, Pages: 104-112, ISSN: 1366-9516
Watson OJ, Verity R, Okell L, et al., 2017, CHARACTERIZING THE POTENTIAL BIAS WITHIN GENOMIC TOOLS FOR INFERRING CHANGES IN <i>PLASMODIUM FALCIPARUM</i> TRANSMISSION INTENSITIES, 66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 418-418, ISSN: 0002-9637
Verity R, Watson O, Doctor S, et al., 2017, VARIATION AT THE VAR2CSA LOCUS: RESULTS FROM A CROSS-SECTIONAL STUDY IN DEMOCRATIC REPUBLIC OF CONGO, 66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 322-322, ISSN: 0002-9637
Parr JB, Verity R, Doctor SM, et al., 2016, Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of the Congo: a national cross-sectional survey, Journal of Infectious Diseases, Vol: 216, Pages: 36-44, ISSN: 0022-1899
Background.Rapid diagnostic tests (RDTs) account for more than two-thirds of malaria diagnoses in Africa. Deletions of the Plasmodium falciparum hrp2 (pfhrp2) gene cause false-negative RDT results and have never been investigated on a national level. Spread of pfhrp2-deleted P. falciparum mutants, resistant to detection by HRP2-based RDTs, would represent a serious threat to malaria elimination efforts.Methods.Using a nationally representative cross-sectional study of 7,137 children under five years of age from the Democratic Republic of Congo (DRC), we tested 783 subjects with RDT-/PCR+ results using PCR assays to detect and confirm deletions of the pfhrp2 gene. Spatial and population genetic analyses were employed to examine the distribution and evolution of these parasites.Results.We identified 149 pfhrp2-deleted parasites, representing 6.4% of all P. falciparum infections country-wide (95% confidence interval 5.1–8.0%). Bayesian spatial analyses identified statistically significant clustering of pfhrp2 deletions near Kinshasa and Kivu. Population genetic analysis revealed significant genetic differentiation between wild-type and pfhrp2-deleted parasite populations (GST = .046, p ≤ .00001).Conclusions.Pfhrp2-deleted P. falciparum is a common cause of RDT-/PCR+ malaria among asymptomatic children in the DRC and appears to be clustered within select communities. Surveillance for these deletions is needed, and alternatives to HRP2-specific RDTs may be necessary.
Verity R, Nichols RA, 2016, Estimating the Number of Subpopulations ( K ) in Structured Populations, Genetics, Vol: 203, Pages: 1827-1839, ISSN: 0016-6731
Penny MA, Verity RV, Bever C, et al., 2015, Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models, The Lancet, Vol: 387, Pages: 367-375, ISSN: 0140-6736
BackgroundThe phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings.MethodsWe compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5–17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2–10 year olds (PfPR2–10; range 3–65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2–10 per dose.FindingsIn regions with a PfPR2–10 of 10–65%, RTS,S/AS01 is predicted to avert a median of 93 940 (range 20 490–126 540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116 480 (31 450–160 410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children. A positive impact is also predicted at a PfPR2–10 of 5–10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2–10 of 10–65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18–2
White MT, Verity R, Churcher TS, et al., 2015, Vaccine approaches to malaria control and elimination: Insights from mathematical models, Vaccine, Vol: 33, Pages: 7544-7550, ISSN: 1873-2518
A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts.Several candidate vaccines targeting different stages ofthe malaria parasite’s lifecycle are currently underdevelopment, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection,having recently completed Phase III trials. Predicting the public health impact of a candidate malariavaccine requires using clinical trial data to estimate the vaccine’s efficacy profile—the initial efficacyfollowing vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacyprofile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematicalmodels.Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocyticvaccines and transmission-blocking vaccines from clinicaltrial data. In the case of RTS,S/AS01, model estimatesfrom Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection,with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waningover the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II orPhase III clinical trials so we review ongoing work investigating how a clinical trial might be designed toensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstratehow parameters estimated from clinical trials can be used to predict the impact of vaccination campaignson malaria using a mathematical model of malaria transmission
White MT, Verity R, Griffin JT, et al., 2015, Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial, Lancet Infectious Diseases, Vol: 15, Pages: 1450-1458, ISSN: 1473-3099
BackgroundThe RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014.MethodsUsing data from 8922 African children aged 5–17 months and 6537 African infants aged 6–12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time.FindingsRTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5–17 months than in those aged 6–12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6–12 weeks and higher immunogenicity in those aged 5–17 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5–17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42–48) and that of the long-lived component was 591 days (557–632). After primary vaccination 12% (11–13) of the response was estimated to be long-lived, rising to 30% (28–32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98–153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and effi
McCarthy EW, Arnold SEJ, Chittka L, et al., 2015, The effect of polyploidy and hybridization on the evolution of floral colour in Nicotiana (Solanaceae), Annals of Botany, Vol: 115, Pages: 1117-1131, ISSN: 0305-7364
Faulkner SC, Stevenson MD, Verity R, et al., 2015, Using geographic profiling to locate elusive nocturnal animals: a case study with spectral tarsiers, JOURNAL OF ZOOLOGY, Vol: 295, Pages: 261-268, ISSN: 0952-8369
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Verity R, Nichols RA, 2014, What is genetic differentiation, and how should we measure it-<i>G</i><sub>ST</sub>, <i>D</i>, neither or both?, MOLECULAR ECOLOGY, Vol: 23, Pages: 4216-4225, ISSN: 0962-1083
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Verity R, Stevenson MD, Rossmo DK, et al., 2014, Spatial targeting of infectious disease control: identifying multiple, unknown sources, METHODS IN ECOLOGY AND EVOLUTION, Vol: 5, Pages: 647-655, ISSN: 2041-210X
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- Citations: 28
Verity R, Marquardt J, Hatlen A, et al., 2013, From hybrids to hermaphrodites in population genetics, Genome Biology, Vol: 14, Pages: 1-3, ISSN: 1474-7596
A report on the 46th annual PopGroup conference,Glasgow, UK, December 18-21, 2012
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