Imperial College London

DrLucyOkell

Faculty of MedicineSchool of Public Health

Lecturer/Royal Society Dorothy Hodgkin Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 3265l.okell Website

 
 
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Location

 

G24Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

45 results found

Slater HC, Ross A, Felger I, Hofmann NE, Robinson L, Cook J, Goncalves BP, Bjorkman A, Ouedraogo AL, Morris U, Msellem M, Koepfli C, Mueller I, Tadesse F, Gadisa E, Das S, Domingo G, Kapulu M, Midega J, Owusu-Agyei S, Nabet C, Piarroux R, Doumbo O, Doumbo SN, Koram K, Lucchi N, Udhayakumar V, Mosha J, Tiono A, Chandramohan D, Gosling R, Mwingira F, Sauerwein R, Paul R, Riley EM, White NJ, Nosten F, Imwong M, Bousema T, Drakeley C, Okell LCet al., 2019, Author Correction: The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density, Nature Communications, Vol: 10, ISSN: 2041-1723

Correction to: Nature Communications https://doi.org/10.1038/s41467-019-09441-1; published online 29 March 2019

Journal article

Slater H, Ross A, Felger I, Hofmann N, Robinson L, Cook J, Goncalves, Bjorkman, Ouedraogo, Morris, Msellem, Koepfli, Mueller, Tadesse, Gadisa, Das, Domingo, Kapulu, Midega J, Owusu-Agyei, Nabet, Piarroux, Doumbo, Doumbo, Koram, Lucchi, Udhayakumar, Mosha, Tiono, Chandramohan, Gosling, Mwingira, Sauerwein, Riley, White, Nosten, Imwong, Bousema, Drakeley, Okell Let al., 2019, The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density, Nature Communications, Vol: 10, ISSN: 2041-1723

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings.

Journal article

van Eijk AM, Larsen DA, Kayentao K, Koshy G, Slaughter DEC, Roper C, Okell LC, Desai M, Gutman J, Khairallah C, Rogerson SJ, Hopkins Sibley C, Meshnick SR, Taylor SM, Ter Kuile FOet al., 2019, Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis., Lancet Infectious Diseases, ISSN: 1473-3099

BACKGROUND: Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) in sub-Saharan Africa. We aimed to assess the associations between markers of sulfadoxine-pyrimethamine resistance in P falciparum and the effectiveness of sulfadoxine-pyrimethamine IPTp for malaria-associated outcomes. METHODS: For this systematic review and meta-analysis, we searched databases (from Jan 1, 1990 to March 1, 2018) for clinical studies (aggregated data) or surveys (individual participant data) that reported data on low birthweight (primary outcome) and malaria by sulfadoxine-pyrimethamine IPTp dose, and for studies that reported on molecular markers of sulfadoxine-pyrimethamine resistance. Studies that involved only HIV-infected women or combined interventions were excluded. We did a random-effects meta-analysis (clinical studies) or multivariate log-binomial regression (surveys) to obtain summarised dose-response data (relative risk reduction [RRR]) and multivariate meta-regression to explore the modifying effects of sulfadoxine-pyrimethamine resistance (as indicated by Ala437Gly, Lys540Glu, and Ala581Gly substitutions in the dhps gene). This study is registered with PROSPERO, number 42016035540. FINDINGS: Of 1097 records screened, 57 studies were included in the aggregated-data meta-analysis (including 59 457 births). The RRR for low birthweight declined with increasing prevalence of dhps Lys540Glu (ptrend=0·0060) but not Ala437Gly (ptrend=0·35). The RRR was 7% (95% CI 0 to 13) in areas of high resistance to sulfadoxine-pyrimethamine (Lys540Glu ≥90% in east and southern Africa; n=11), 21% (14 to 29) in moderate-resistance areas (Ala437Gly ≥90% [central and west Africa], or Lys540Glu ≥30% to <90% [east and southern Africa]; n=16), and 27% (21 to 33) in low-resistance areas (Ala437Gly <90% [central and west Africa], or Lys540Glu <30% [east and

Journal article

van Eijk AM, Larsen D, Kayentao K, Koshy G, Slaughter D, Roper C, Okell L, Desai M, Gutman J, Khairallah C, Rogerson S, Sibley C, Meshnick S, Taylor S, ter Kuile Fet al., Impact of Plasmodium falciparum Sulphadoxine-Pyrimethamine Resistance on the Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy in Africa: A Systematic Review and Meta-Analysis, Lancet Infectious Diseases, ISSN: 1473-3099

BackgroundPlasmodium falciparum resistance to sulphadoxine-pyrimethamine (SP) threatens the efficacy of intermittent preventive treatment (IPTp) for malaria in pregnancy in Africa. We conducted a meta-analysis to assess the impact of SP resistance on IPTp-SP effectiveness.MethodsWe searched databases (1990 to March-01-2018) for clinical studies (aggregated data) or surveys (individual-participant data) containing information on low birthweight (LBW, primary outcome) and malaria by IPTp-SP dose, and for studies reporting SP-resistance molecular markers. We performed random-effects meta-analysis (clinical studies) or multivariate log-binomial regression (surveys) to obtain summarized dose-response data (Relative-Risk-Reduction:RRR) and multivariate meta-regression to explore modifying effects of SP-resistance (dhps substitutions A437G, K540E, A581G). FindingsOf 1097 records, 57 studies were included in the aggregated-data meta-analysis (59,457 births). The RRR for LBW declined with increasing prevalence of Pfdhps-K540E (P-trend=0.0060) but not with Pfdhps-A437G (P-trend=0.35). The RRR in areas of high (Pfdhps-K540E >90%, n=11), moderate (Central/West Africa:Pfdhps-A437G≥90% or East/southern Africa:Pfdhps-K540E 30-90%, n=16) and low SP-resistances (n=30) were 7% (95% CI 0-13), 21% (14-29) and 27% (21-33) respectively (P-trend=0.0054, I2=69.5%). In the individual-participant analysis of 13 surveys (42,394 births), IPTp-SP was associated with reduced LBW in areas with Pfdhps-K540E>90% & Pfdhps-A581G<10% (RRR=10%, 7-12), but not those with Pfdhps-A581G>=10% (pooled Pfdhps-A581G prevalence:37%, range 29-46) (RRR=0.5%, -16-14, n=3). InterpretationThe effectiveness of IPTp-SP is reduced in areas with high SP-resistance, but IPTp-SP remains associated with reduced LBW in areas where Pfdhps-K540E prevalence exceeds 90%. IPTp-SP is not effective in areas with ≥37% prevalence of the highly-resistant sextuple Pfdhps-A581G-containing genotype.

Journal article

Okell L, Reiter LM, Ebbe LS, Baraka V, Bisanzio D, Watson O, Bennett A, Verity R, Gething P, Roper C, Alifrangis Met 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

Journal article

Tadesse FG, Slater HC, Chali W, Teelen K, Lanke K, Belachew M, Menberu T, Shumie G, Shitaye G, Okell LC, Graumans W, van Gemert G-J, Kedir S, Tesfaye A, Belachew F, Abebe W, Mamo H, Sauerwein R, Balcha T, Aseffa A, Yewhalaw D, Gadisa E, Drakeley C, Bousema Tet al., 2018, The relative contribution of symptomatic and asymptomatic Plasmodium vivax and Plasmodium falciparum infections to the infectious reservoir in a low-endemic setting in Ethiopia, Clinical Infectious Diseases, Vol: 66, Pages: 1883-1891, ISSN: 1058-4838

Background: The majority of P. vivax and P. falciparum infections in low-endemic settings are asymptomatic. The relative contribution to the infectious reservoir of these infections, often of low-parasite-density, compared to clinical malaria cases, is currently unknown but important for malaria elimination strategies. Methods: We assessed infectivity of passively-recruited symptomatic malaria patients (n=41) and community-recruited asymptomatic individuals with microscopy- (n=41) and PCR-detected infections (n=82) using membrane feeding assays with Anopheles arabiensis mosquitoes in Adama, Ethiopia. Malaria incidence and prevalence data was used to estimate the contributions of these populations to the infectious reservoir. Results: Overall, 34.9% (29/83) of P. vivax and 15.1% (8/53) P. falciparum infected individuals infected ≥1 mosquitoes. Mosquito infection rates were strongly correlated with asexual parasite density for P. vivax (ρ = 0.63; P < .001) but not for P. falciparum (ρ = 0.06; P = .770). P. vivax symptomatic infections were more infectious to mosquitoes (infecting 46.5% of mosquitoes, 307/660) compared to asymptomatic microscopy-detected (infecting 12.0% of mosquitoes, 80/667; P = .005) and PCR-detected infections (infecting 0.8% of mosquitoes, 6/744; P < .001). Adjusting for population prevalence, symptomatic, asymptomatic microscopy- and PCR-detected infections were responsible for 8.0%, 76.2% and 15.8% of the infectious reservoir for P. vivax, respectively. For P. falciparum, mosquito infections were sparser and also predominantly from asymptomatic infections. Conclusions: In this low-endemic setting aiming for malaria elimination, asymptomatic infections are highly prevalent and responsible for the majority of onward mosquito infections. The early identification and treatment of asymptomatic infections might thus accelerate elimination efforts.

Journal article

Challenger J, Bruxvoort K, Ghani AC, Okell LCet al., 2017, Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling, Nature Communications, Vol: 8, ISSN: 2041-1723

Artemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicated Plasmodium falciparum malaria worldwide. Its safety and efficacy have been extensively demonstrated in clinical trials; however, its performance in routine health care settings, where adherence to drug treatment is unsupervised and therefore may be suboptimal, is less well characterised. Here we develop a within-host modelling framework for estimating the effects of sub-optimal adherence to AL treatment on clinical outcomes in malaria patients. Our model incorporates data on the human immune response to the parasite, and AL’s pharmacokinetic and pharmacodynamic properties. Utilising individual-level data of adherence to AL in 482 Tanzanian patients as input for our model predicted higher rates of treatment failure than were obtained when adherence was optimal (9% compared to 4%). Our model estimates that the impact of imperfect adherence was worst in children, highlighting the importance of advice to caregivers.

Journal article

Brady OJ, Slater HC, Pemberton-Ross P, Wenger E, Maude RJ, Ghani AC, Penny MA, Gerardin J, White LJ, Chitnis N, Aguas R, Hay SI, Smith DL, Stuckey EM, Okiro EA, Smith TA, Okell LCet al., 2017, Model citizen Reply, LANCET GLOBAL HEALTH, Vol: 5, Pages: E974-E974, ISSN: 2214-109X

Journal article

Bretscher MT, Griffin JT, Ghani AC, Okell LCet al., 2017, Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment, MALARIA JOURNAL, Vol: 16, ISSN: 1475-2875

BackgroundAnti-malarial drugs are an important tool for malaria control and elimination. Alongside their direct benefit in the treatment of disease, drug use has a community-level effect, clearing the reservoir of infection and reducing onward transmission of the parasite. Different compounds potentially have different impacts on transmission—with some providing periods of prolonged chemoprophylaxis whilst others have greater transmission-blocking potential. The aim was to quantify the relative benefit of such properties for transmission reduction to inform target product profiles in the drug development process and choice of first-line anti-malarial treatment in different endemic settings.MethodsA mathematical model of Plasmodium falciparum epidemiology was used to estimate the transmission reduction that can be achieved by using drugs of varying chemoprophylactic (protection for 3, 30 or 60 days) or transmission-blocking activity (blocking 79, 92 or 100% of total onward transmission). Simulations were conducted at low, medium or high transmission intensity (slide-prevalence in 2–10 year olds being 1, 10 or 40%, respectively), with drugs administered either via case management or mass drug administration (MDA).ResultsTransmission reductions depend strongly on deployment strategy, treatment coverage and endemicity level. Transmission-blocking was most effective at low endemicity, whereas chemoprophylaxis was most useful at high endemicity levels. Increasing the duration of protection as much as possible was beneficial. Increasing transmission-blocking activity from the level of ACT to a 100% transmission-blocking drug (close to the effect estimated for ACT combined with primaquine) produced moderate impact but was not as effective as increasing the duration of protection in medium-to-high transmission settings (slide prevalence 10–40%). Combining both good transmission-blocking activity (e.g. as achieved by ACT or ACT + primaquine) and a long durat

Journal article

Okell L, Griffin JT, Roper C, 2017, Mapping sulphadoxine-pyrimethamine-resistant Plasmodium falciparum malaria in infected humans and in parasite populations in Africa, Scientific Reports, Vol: 7, ISSN: 2045-2322

Intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine in vulnerable populations reduces malaria morbidity in Africa, but resistance mutations in the parasite dhps gene (combined with dhfr mutations) threaten its efficacy. We update a systematic review to map the prevalence of K540E and A581G mutations in 294 surveys of infected humans across Africa from 2004-present. Interpreting these data is complicated by multiclonal infections in humans, especially in high transmission areas. We extend statistical methods to estimate the frequency, i.e. the proportion of resistant clones in the parasite population at each location, and so standardise for varying transmission levels. Both K540E and A581G mutations increased in prevalence and frequency in 60% of areas after 2008, highlighting the need for ongoing surveillance. Resistance measures within countries were similar within 300 km, suggesting an appropriate spatial scale for surveillance. Spread of the mutations tended to accelerate once their prevalence exceeded 10% (prior to fixation). Frequencies of resistance in parasite populations are the same or lower than prevalence in humans, so more areas would be classified as likely to benefit from IPT if similar frequency thresholds were applied. We propose that the use of resistance frequencies as well as prevalence measures for policy decisions should be evaluated.

Journal article

Brady OJ, Slater HC, Pemberton-Ross P, Wenger E, Maude RJ, Ghani AC, Penny MA, Gerardin J, White LJ, Chitnis N, Aguas R, Hay SI, Smith DL, Stuckey EM, Okiro EA, Smith TA, Okell LCet al., 2017, Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study, The Lancet Global Health, Vol: 5, Pages: E680-E687, ISSN: 2214-109X

BackgroundMass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission.MethodsWe collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration.FindingsThe models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest.InterpretationMass drug administration has the potential to reduce transmission for a limited time, but is not an

Journal article

Okell LC, Churcher TS, 2016, Generating the evidence base for malaria elimination: the situation in Haiti, Lancet Global Health, Vol: 5, Pages: e16-e17, ISSN: 2214-109X

Journal article

Slater HC, Okell LC, Ghani AC, 2016, Mathematical Modelling to Guide Drug Development for Malaria Elimination, Trends in Parasitology, Vol: 33, Pages: 175-184, ISSN: 1471-5007

Mathematical models of the dynamics of a drug within the host are now frequently used to guide drug development. These generally focus on assessing the efficacy and duration of response to guide patient therapy. Increasingly, antimalarial drugs are used at the population level, to clear infections, provide chemoprevention, and to reduce onward transmission of infection. However, there is less clarity on the extent to which different drug properties are important for these different uses. In addition, the emergence of drug resistance poses new threats to longer-term use and highlights the need for rational drug development. Here, we argue that integrating within-host pharmacokinetic and pharmacodynamic (PK/PD) models with mathematical models for the population-level transmission of malaria is key to guiding optimal drug design to aid malaria elimination.

Journal article

Slater HC, Griffin JT, Ghani AC, Okell LCet al., 2016, Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa., Malaria Journal, Vol: 15, ISSN: 1475-2875

BACKGROUND: Artemisinin and partner drug resistant malaria parasites have emerged in Southeast Asia. If resistance were to emerge in Africa it could have a devastating impact on malaria-related morbidity and mortality. This study estimates the potential impact of artemisinin and partner drug resistance on disease burden in Africa if it were to emerge. METHODS: Using data from Asia and Africa, five possible artemisinin and partner drug resistance scenarios are characterized. An individual-based malaria transmission model is used to estimate the impact of each resistance scenario on clinical incidence and parasite prevalence across Africa. Artemisinin resistance is characterized by slow parasite clearance and partner drug resistance is associated with late clinical failure or late parasitological failure. RESULTS: Scenarios with high levels of recrudescent infections resulted in far greater increases in clinical incidence compared to scenarios with high levels of slow parasite clearance. Across Africa, it is estimated that artemisinin and partner drug resistance at levels similar to those observed in Oddar Meanchey province in Cambodia could result in an additional 78 million cases over a 5 year period, a 7 % increase in cases compared to a scenario with no resistance. A scenario with high levels of slow clearance but no recrudescence resulted in an additional 10 million additional cases over the same period. CONCLUSION: Artemisinin resistance is potentially a more pressing concern than partner drug resistance due to the lack of viable alternatives. However, it is predicted that a failing partner drug will result in greater increases in malaria cases and morbidity than would be observed from artemisinin resistance only.

Journal article

Wu L, van den Hoogen LL, Slater H, Walker PGT, Ghani AC, Drakeley CJ, Okell LCet al., 2015, Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies, Nature, Vol: 528, Pages: S86-S93, ISSN: 0028-0836

The global burden of malaria has been substantially reduced over the past two decades. Future efforts to reduce malaria further will require moving beyond the treatment of clinical infections to targeting malaria transmission more broadly in the community. As such, the accurate identification of asymptomatic human infections, which can sustain a large proportion of transmission, is becoming a vital component of control and elimination programmes. We determined the relationship across common diagnostics used to measure malaria prevalence — polymerase chain reaction (PCR), rapid diagnostic test and microscopy — for the detection of Plasmodium falciparum infections in endemic populations based on a pooled analysis of cross-sectional data. We included data from more than 170,000 individuals comparing the detection by rapid diagnostic test and microscopy, and 30,000 for detection by rapid diagnostic test and PCR. The analysis showed that, on average, rapid diagnostic tests detected 41% (95% confidence interval = 26–66%) of PCR-positive infections. Data for the comparison of rapid diagnostic test to PCR detection at high transmission intensity and in adults were sparse. Prevalence measured by rapid diagnostic test and microscopy was comparable, although rapid diagnostic test detected slightly more infections than microscopy. On average, microscopy captured 87% (95% confidence interval = 74–102%) of rapid diagnostic test-positive infections. The extent to which higher rapid diagnostic test detection reflects increased sensitivity, lack of specificity or both, is unclear. Once the contribution of asymptomatic individuals to the infectious reservoir is better defined, future analyses should ideally establish optimal detection limits of new diagnostics for use in control and elimination strategies.

Journal article

Cairns ME, Walker PGT, Okell LC, Griffin JT, Garske T, Asante KP, Owusu-Agyei S, Diallo D, Dicko A, Cisse B, Greenwood BM, Chandramohan D, Ghani AC, Milligan PJet al., 2015, Seasonality in malaria transmission: implications for case-management with long-acting artemisinin combination therapy in sub-Saharan Africa, Malaria Journal, Vol: 14, ISSN: 1475-2875

Background: Long-acting artemisinin-based combination therapy (LACT) offers the potential to prevent recurrentmalaria attacks in highly exposed children. However, it is not clear where this advantage will be most important, anddeployment of these drugs is not rationalized on this basis.Methods: To understand where post-treatment prophylaxis would be most beneficial, the relationship betweenseasonality, transmission intensity and the interval between malaria episodes was explored using data from six cohortstudies in West Africa and an individual-based malaria transmission model. The total number of recurrent malariacases per 1000 child-years at risk, and the fraction of the total annual burden that this represents were estimated forsub-Saharan Africa.Results: In settings where prevalence is less than 10 %, repeat malaria episodes constitute a small fraction of thetotal burden, and few repeat episodes occur within the window of protection provided by currently available drugs.However, in higher transmission settings, and particularly in high transmission settings with highly seasonal transmis‑sion, repeat malaria becomes increasingly important, with up to 20 % of the total clinical burden in children estimatedto be due to repeat episodes within 4 weeks of a prior attack.Conclusion: At a given level of transmission intensity and annual incidence, the concentration of repeat malariaepisodes in time, and consequently the protection from LACT is highest in the most seasonal areas. As a result, thedegree of seasonality, in addition to the overall intensity of transmission, should be considered by policy makers whendeciding between ACT that differ in their duration of post-treatment prophylaxis.

Journal article

Slater HC, Walker PGT, Bousema T, Okell LC, Ghani ACet al., 2014, The Potential Impact of Adding Ivermectin to a Mass Treatment Intervention to Reduce Malaria Transmission: A Modelling Study, JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: 1972-1980, ISSN: 0022-1899

Journal article

Bousema T, Okell L, Felger I, Drakeley Cet al., 2014, Asymptomatic malaria infections: detectability, transmissibility and public health relevance, NATURE REVIEWS MICROBIOLOGY, Vol: 12, Pages: 833-840, ISSN: 1740-1526

Journal article

Okell LC, Cairns M, Griffin JT, Ferguson NM, Tarning J, Jagoe G, Hugo P, Baker M, D'Alessandro U, Bousema T, Ubben D, Ghani ACet al., 2014, Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis, Nature Communications, Vol: 5, ISSN: 2041-1723

There are currently several recommended drug regimens for uncomplicated falciparummalaria in Africa. Each has different properties that determine its impact on diseaseburden. Two major antimalarial policy options are artemether–lumefantrine (AL) anddihydroartemisinin–piperaquine (DHA–PQP). Clinical trial data show that DHA–PQP provideslonger protection against reinfection, while AL is better at reducing patient infectiousness.Here we incorporate pharmacokinetic-pharmacodynamic factors, transmission-reducingeffects and cost into a mathematical model and simulate malaria transmission and treatmentin Africa, using geographically explicit data on transmission intensity and seasonality,population density, treatment access and outpatient costs. DHA–PQP has a modestly higherestimated impact than AL in 64% of the population at risk. Given current higher costestimates for DHA–PQP, there is a slightly greater cost per case averted, except in areas withhigh, seasonally varying transmission where the impact is particularly large. We find that alocally optimized treatment policy can be highly cost effective for reducing clinical malariaburden.

Journal article

Bretscher MT, Griffin JT, Hugo P, Baker M, Ghani A, Okell Let al., 2014, A comparison of the duration of post-treatment protection of artemether-lumefantrine, dihydroartemisinin-piperaquine and artesunate-amodiaquine for the treatment of uncomplicated malaria

Poster

Tietje K, Hawkins K, Clerk C, Ebels K, McGray S, Crudder C, Okell L, LaBarre Pet al., 2014, The essential role of infection-detection technologies for malaria elimination and eradication, TRENDS IN PARASITOLOGY, Vol: 30, Pages: 259-266, ISSN: 1471-4922

Journal article

Beshir KB, Sutherland CJ, Sawa P, Drakeley CJ, Okell L, Mweresa CK, Omar SA, Shekalaghe SA, Kaur H, Ndaro A, Chilongola J, Schallig HDFH, Sauerwein RW, Hallett RL, Bousema Tet al., 2013, Residual Plasmodium falciparum Parasitemia in Kenyan Children After Artemisinin-Combination Therapy Is Associated With Increased Transmission to Mosquitoes and Parasite Recurrence, JOURNAL OF INFECTIOUS DISEASES, Vol: 208, Pages: 2017-2024, ISSN: 0022-1899

Journal article

Sawa P, Shekalaghe SA, Drakeley CJ, Sutherland CJ, Mweresa CK, Baidjoe AY, Manjurano A, Kavishe RA, Beshir KB, Yussuf RU, Omar SA, Hermsen CC, Okell L, Schallig HDFH, Sauerwein RW, Hallett RL, Bousema Tet al., 2013, Malaria Transmission After Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine: A Randomized Trial, JOURNAL OF INFECTIOUS DISEASES, Vol: 207, Pages: 1637-1645, ISSN: 0022-1899

Journal article

Okell LC, Bousema T, Griffin JT, Ouedraogo AL, Ghani AC, Drakeley CJet al., 2012, Factors determining the occurrence of submicroscopic malaria infections and their relevance for control, NATURE COMMUNICATIONS, Vol: 3, ISSN: 2041-1723

Journal article

Okell LC, Paintain LS, Webster J, Hanson K, Lines Jet al., 2012, From intervention to impact: modelling the potential mortality impact achievable by different long-lasting, insecticide-treated net delivery strategies, MALARIA JOURNAL, Vol: 11, ISSN: 1475-2875

Journal article

Manjurano A, Okell L, Lukindo T, Reyburn H, Olomi R, Roper C, Clark TG, Joseph S, Riley EM, Drakeley Cet al., 2011, Association of sub-microscopic malaria parasite carriage with transmission intensity in north-eastern Tanzania, MALARIA JOURNAL, Vol: 10, ISSN: 1475-2875

Journal article

Gosling RD, Okell L, Mosha J, Chandramohan Det al., 2011, The role of antimalarial treatment in the elimination of malaria, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 17, Pages: 1617-1623, ISSN: 1198-743X

Journal article

Shekalaghe SA, Drakeley C, van den Bosch S, ter Braak R, van den Bijllaardt W, Mwanziva C, Semvua S, Masokoto A, Mosha F, Teelen K, Hermsen R, Okell L, Gosling R, Sauerwein R, Bousema Tet al., 2011, A cluster-randomized trial of mass drug administration with a gametocytocidal drug combination to interrupt malaria transmission in a low endemic area in Tanzania, MALARIA JOURNAL, Vol: 10

Journal article

Okell LC, Griffin JT, Kleinschmidt I, Hollingsworth TD, Churcher TS, White MJ, Bousema T, Drakeley CJ, Ghani ACet al., 2011, The Potential Contribution of Mass Treatment to the Control of Plasmodium falciparum Malaria, PLOS ONE, Vol: 6, ISSN: 1932-6203

Journal article

Cairns M, Ghani A, Okell L, Gosling R, Carneiro I, Anto F, Asoala V, Owusu-Agyei S, Greenwood B, Chandramohan D, Milligan Pet al., 2011, Modelling the Protective Efficacy of Alternative Delivery Schedules for Intermittent Preventive Treatment of Malaria in Infants and Children, PLOS ONE, Vol: 6, ISSN: 1932-6203

Journal article

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