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Hossain MB, Rahman MS, Watson OJ, et al., 2020, Epidemiology and genotypes of group A rotaviruses in cattle and goats of Bangladesh, 2009-2010, INFECTION GENETICS AND EVOLUTION, Vol: 79, ISSN: 1567-1348
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Ainslie K, Walters C, Fu H, et al., 2020, Report 11: Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment
The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. As of 20 March 2020, over 254,000 cases and 10,000 deaths had been reported worldwide. The outbreak began in the Chinese city of Wuhan in December 2019. In response to the fast-growing epidemic, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. At the peak of the outbreak in China (early February), there were between 2,000 and 4,000 new confirmed cases per day. For the first time since the outbreak began there have been no new confirmed cases caused by local transmission in China reported for five consecutive days up to 23 March 2020. This is an indication that the social distancing measures enacted in China have led to control of COVID-19 in China. These interventions have also impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic is not yet clear. Here, we estimate transmissibility from reported cases and compare those estimates with daily data on within-city movement, as a proxy for economic activity. Initially, within-city movement and transmission were very strongly correlated in the 5 provinces most affected by the epidemic and Beijing. However, that correlation is no longer apparent even though within-city movement has started to increase. A similar analysis for Hong Kong shows that intermediate levels of local activity can be maintained while avoiding a large outbreak. These results do not preclude future epidemics in China, nor do they allow us to estimate the maximum proportion of previous within-city activity that will be recovered in the medium term. However, they do suggest that after very intense social distancing which resulted in containment, China has successfully exited their stringent social distancing policy to some degree. Globally, China is at a more advanced stage of the pandemic. Policies implemented to reduce the spread of CO
Brazeau NF, Mitchell CL, Morgan AP, et al., 2020, The Epidemiology of <i>Plasmodium vivax</i> Among Adults in the Democratic Republic of the Congo: A Nationally-Representative, Cross-Sectional Survey
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Reports of <jats:italic>P. vivax</jats:italic> infections among Duffy-negative hosts have begun to accumulate throughout sub-Saharan Africa. Despite this growing body of evidence, no nationally representative epidemiological surveys of <jats:italic>P. vivax</jats:italic> in sub-Saharan Africa nor population genetic analyses to determine the source of these infections have been performed.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>To overcome this critical gap in knowledge, we screened nearly 18,000 adults in the Democratic Republic of the Congo (DRC) for <jats:italic>P. vivax</jats:italic> using samples from the 2013-2014 Demographic Health Survey. Infections were identified by quantitative PCR and confirmed with nested-PCR. <jats:italic>P. vivax</jats:italic> mitochondrial genomes were constructed after short-read sequencing. Risk factors, spatial distributions and population genetic analyses were explored.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Overall, we found a 2.96% (95% CI: 2.28%, 3.65%) prevalence of <jats:italic>P. vivax</jats:italic> infections across the DRC. Nearly all infections were among Duffy-negative adults (486/489). Infections were not associated with typical malaria risk-factors and demonstrated small-scale heterogeneity in prevalence across space. Mitochondrial genomes suggested that DRC <jats:italic>P. vivax</jats:italic> is an older clade that shares its most recent common ancestor with South American isolates.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p><jats:italic>P. vivax</jats:italic> is more prevalent across the DRC than previously believed d
Witmer K, Dahalan FA, Delves MJ, et al., 2020, Artemisinin-resistant malaria parasites show enhanced transmission to mosquitoes under drug pressure
<jats:title>ABSTRACT</jats:title><jats:p>Resistance to artemisinin combination therapy (ACT) in the <jats:italic>Plasmodium falciparum</jats:italic> parasite is threatening to reverse recent gains in reducing global deaths from malaria. Whilst resistance manifests as delayed asexual parasite clearance in patients following ACT treatment, the phenotype can only spread geographically via the sexual cycle and subsequent transmission through the mosquito. Artemisinin and its derivatives (such as dihydroartemisinin, DHA) as well as killing the asexual parasite form are known to sterilize male, sexual-stage gametes from activation. Whether resistant parasites overcome this artemisinin-dependent sterilizing effect has not, however, been fully tested. Here, we analysed five <jats:italic>P. falciparum</jats:italic> clinical isolates from the Greater Mekong Subregion, each of which demonstrated delayed clinical clearance and carried known resistance-associated polymorphisms in the <jats:italic>Kelch13</jats:italic> gene (PfK13<jats:sup>var</jats:sup>). As well as demonstrating reduced sensitivity to artemisinin-derivates in <jats:italic>in vitro</jats:italic> asexual growth assays, certain PfK13<jats:sup>var</jats:sup> isolates also demonstrated a marked reduction in sensitivity to these drugs in an <jats:italic>in vitro</jats:italic> male gamete activation assay compared to a sensitive control. Importantly, the same reduction in sensitivity to DHA was observed when the most resistant isolate was assayed by standard membrane feeding assays using <jats:italic>Anopheles stephensi</jats:italic> mosquitoes. These results indicate that ACT use can favour resistant over sensitive parasite transmission. A selective advantage for resistant parasite transmission could also favour acquisition of further polymorphisms, such as mosquito host-specificity or antimalarial partne
Akala HM, Watson O, Mitei KK, et al., 2020, Longitudinal characterization of <i>Plasmodium</i> inter-species interactions during a period of increasing prevalence of <i>Plasmodium ovale</i>
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The epidemiology and severity of non-falciparum malaria in endemic settings has garnered limited attention. We aimed to characterize the prevalence, interaction, clinical risk factors and temporal trends of non-falciparum malaria in endemic settings of Kenya.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We diagnosed and analyzed infecting malaria species via PCR in 2027 clinical samples collected between 2008 and 2016. Descriptive statistics were used to describe the prevalence and distribution of <jats:italic>Plasmodium</jats:italic> species. A statistical model was designed and used for estimating the frequency of <jats:italic>Plasmodium</jats:italic> species and assessing inter-species interactions. Mixed effect linear regression models with random intercepts for each location was used to test for change in prevalence over time.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>72•5% of the samples were <jats:italic>P. falciparum</jats:italic> single species infections, 25·8% were mixed infections and only 1•7% occurred as single non-falciparum species infections. 23•1% were mixed infections containing <jats:italic>P. ovale</jats:italic>. A likelihood-based model calculation of the population frequency of each species estimated a significant within-host interference between <jats:italic>P. falciparum</jats:italic> and <jats:italic>P. ovale curtisi</jats:italic>. Mixed-effect logistic regression models identified a significant increase of <jats:italic>P. ovale wallikeri</jats:italic> and <jats:italic>P. ovale curtisi</jats:italic> species over time with reciprocal decrease in <jats:italic>P. falciparum single
Smith TP, Flaxman S, Gallinat AS, et al., 2020, Environment influences SARS-CoV-2 transmission in the absence of non-pharmaceutical interventions, medRxiv
Watson OJ, Okell LC, Hellewell J, et al., 2019, Evaluating the performance of malaria genomics for inferring changes in transmission intensity using transmission modelling
<jats:title>Abstract</jats:title><jats:p>Advances in genetic sequencing and accompanying methodological approaches have resulted in pathogen genetics being used in the control of infectious diseases. To utilise these methodologies for malaria we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment. Here we develop an individual-based transmission model to simulate malaria parasite genetics parameterised using estimated relationships between complexity of infection and age from 5 regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterise the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The best performing model successfully predicted malaria prevalence with mean absolute error of 0.055, suggesting genetic tools could be used for monitoring the impact of malaria interventions.</jats:p>
Watson O, Sumner K, Janko M, et al., 2019, False-negative malaria rapid diagnostic test results and their impact on community-based malaria surveys in sub- Saharan Africa, BMJ Global Health, Vol: 4, Pages: 1-9, ISSN: 2059-7908
Surveillance and diagnosis of Plasmodium falciparum malaria relies predominantly on rapid diagnostic tests (RDTs). However, false-negative RDT results are known to occur for a variety of reasons, including operator error, poor storage conditions, pfhrp2/3 gene deletions, poor performance of specific RDT brands and lots, and low-parasite-density infections. We used RDT and microscopy results from 85,000 children enrolled in Demographic Health Surveys and Malaria Indicator Surveys from 2009 to 2015 across 19 countries to explore the distribution of and risk factors for false-negative RDTs in Sub40 Saharan Africa, where malaria’s impact is greatest. We sought to (i) identify spatial and demographic patterns of false-negative RDT (FN-RDT) results, defined as a negative RDT but positive gold-standard microscopy test, and (ii) estimate the percentage of infections missed within community-based malaria surveys due to FN-RDT results. Across all studies, 19.9% [95% CI: 19.0 – 20.9] of microscopy-positive subjects were negative by RDT. The distribution of FN-RDT results was spatially heterogeneous. The variance in FN-RDT results was best explained by the prevalence of malaria, with an increase in FN46 RDT results observed at lower transmission intensities, among younger subjects, and in urban areas. The observed proportion of FN-RDT results was not predicted by differences in RDT brand or lot performance alone. These findings characterise how the probability of detection by RDTs varies in different transmission settings and emphasize the need for careful interpretation of prevalence estimates based on surveys employing RDTs alone. Further studies are needed to characterise the cost-effectiveness of improved malaria diagnostics (e.g. PCR or highly sensitive RDTs) in community52 based surveys, especially in regions of low transmission intensity or high urbanicity.
Watson O, FitzJohn R, Eaton J, 2019, rdhs: an R package to interact with The Demographic and Health Surveys (DHS) Program datasets [version 1; peer review: 1 approved, 1 approved with reservations], Wellcome Open Research, Vol: 4, Pages: 1-13, ISSN: 2398-502X
Since 1985, the Demographic and Health Surveys (DHS) Program has conducted more than 400 surveys in over 90 countries. These surveys provide decision markers with key measures of population demographics, health and nutrition, which allow informed policy evaluation to be made. Though standard health indicators are routinely published in survey final reports, much of the value of DHS is derived from the ability to download and analyse standardised microdata datasets for subgroup analysis, pooled multi-country analysis, and extended research studies. We have developed an open-source freely available R package ‘rdhs’ to facilitate management and processing of DHS survey data. The package provides a suite of tools to (1) access standard survey indicators through the DHS Program API, (2) identify all survey datasets that include a particular topic or indicator relevant to a particular analysis, (3) directly download survey datasets from the DHS website, (4) load datasets and data dictionaries into R, and (5) extract variables and pool harmonised datasets for multi-survey analysis. We detail the core functionality of ‘rdhs’ by demonstrating how the package can be used to firstly compare trends in the prevalence of anaemia among women between countries before conducting secondary analysis to assess for the relationship between education and anemia.
Verity R, Aydemir O, Brazeau NF, et al., 2019, The Impact of Antimalarial Resistance on the Genetic Structure of<i>Plasmodium falciparum</i>in the DRC
<jats:title>ABSTRACT</jats:title><jats:p>The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequenced 2537<jats:italic>Plasmodium falciparum</jats:italic>infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a novel high-throughput genotyping tool. We identified an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identified highly related parasites over large geographic distances, indicative of gene flow and migration. Our results were consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.</jats:p>
Watson OJ, Verity R, Ghani AC, et al., 2019, Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions, eLife, Vol: 8, ISSN: 2050-084X
Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017) we characterised the drivers selecting for pfhrp2/3 deletions, and mapped the regions in Africa with the greatest selection pressure. In February 2018, the World Health Organization issued guidance on investigating suspected false-negative rapid diagnostic tests (RDTs) due to pfhrp2/3 deletions. However, no guidance is provided regarding the timing of investigations. Failure to consider seasonal variation could cause premature decisions to switch to alternative RDTs. In response, we have extended our methods and predict that the prevalence of false-negative RDTs due to pfhrp2/3 deletions is highest when sampling from younger individuals during the beginning of the rainy season. We conclude by producing a map of the regions impacted by seasonal fluctuations in pfhrp2/3 deletions and a database identifying optimum sampling intervals to support malaria control programmes.
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
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
Cremin Í, Watson O, Heffernan A, et al., 2018, An infectious way to teach students about outbreaks, Epidemics, Vol: 23, Pages: 42-48, ISSN: 1755-4365
The study of infectious disease outbreaks is required to train today’s epidemiologists. A typical way to introduce and explain key epidemiological concepts is through the analysis of a historical outbreak. There are, however, few training options that explicitly utilise real-time simulated stochastic outbreaks where the participants themselves comprise the dataset they subsequently analyse. In this paper, we present a teaching exercise in which an infectious disease outbreak is simulated over a five-day period and subsequently analysed. We iteratively developed the teaching exercise to offer additional insight into analysing an outbreak. An R package for visualisation, analysis and simulation of the outbreak data was developed to accompany the practical to reinforce learning outcomes. Computer simulations of the outbreak revealed deviations from observed dynamics, highlighting how simplifying assumptions conventionally made in mathematical models often differ from reality. Here we provide a pedagogical tool for others to use and adapt in their own settings.
Routledge I, Watson OJ, Griffin JT, et al., 2018, Predictive malaria epidemiology, models of malaria transmission and elimination, Encyclopedia of Malaria, Editors: Kremsner, Krishna, Publisher: Springer New York, Pages: 1-7, ISBN: 9781461487579
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.
Watson OJ, Routledge I, Griffin JT, et al., 2018, Predictive Malaria Epidemiology, Models of Malaria Control Interventions and Elimination, Encyclopedia of Malaria, Publisher: Springer New York, Pages: 1-7, ISBN: 9781461487579
Okell L, Watson O, 2018, MULTIPLE FIRST LINE THERAPIES VERSUS REDUCING OVERPRESCRIPTION OF ANTIMALARIALS TO SLOW ANTIMALARIAL RESISTANCE, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 443-443, ISSN: 0002-9637
Watson O, Eaton J, 2018, <it>RDHS</it>: AN R PACKAGE TO INTERACT WITH THE DEMOGRAPHIC AND HEALTH SURVEYS (DHS) PROGRAM DATA SETS, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 661-661, 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
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.
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
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
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