Publications
126 results found
Cairns ME, Walker PGT, Okell LC, et 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.
Slater HC, Walker PGT, Bousema T, et 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
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- Citations: 71
Bousema T, Okell L, Felger I, et al., 2014, Asymptomatic malaria infections: detectability, transmissibility and public health relevance, NATURE REVIEWS MICROBIOLOGY, Vol: 12, Pages: 833-840, ISSN: 1740-1526
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- Citations: 409
Okell LC, Cairns M, Griffin JT, et 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.
Bretscher MT, Griffin JT, Hugo P, et 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
Tietje K, Hawkins K, Clerk C, et 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
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- Citations: 38
Beshir KB, Sutherland CJ, Sawa P, et al., 2013, Residual <i>Plasmodium falciparum</i> 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
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- Citations: 94
Sawa P, Shekalaghe SA, Drakeley CJ, et 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
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- Citations: 86
Okell LC, Bousema T, Griffin JT, et al., 2012, Factors determining the occurrence of submicroscopic malaria infections and their relevance for control, NATURE COMMUNICATIONS, Vol: 3, ISSN: 2041-1723
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- Citations: 415
Okell LC, Paintain LS, Webster J, et 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
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- Citations: 18
Manjurano A, Okell L, Lukindo T, et al., 2011, Association of sub-microscopic malaria parasite carriage with transmission intensity in north-eastern Tanzania, MALARIA JOURNAL, Vol: 10, ISSN: 1475-2875
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- Citations: 50
Gosling RD, Okell L, Mosha J, et al., 2011, The role of antimalarial treatment in the elimination of malaria, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 17, Pages: 1617-1623, ISSN: 1198-743X
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- Citations: 42
Shekalaghe SA, Drakeley C, van den Bosch S, et 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
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- Citations: 58
Okell LC, Griffin JT, Kleinschmidt I, et al., 2011, The Potential Contribution of Mass Treatment to the Control of <i>Plasmodium falciparum</i> Malaria, PLOS ONE, Vol: 6, ISSN: 1932-6203
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- Citations: 103
Cairns M, Ghani A, Okell L, et 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
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- Citations: 11
Wipasa J, Okell L, Sakkhachornphop S, et al., 2011, Short-Lived IFN-γ Effector Responses, but Long-Lived IL-10 Memory Responses, to Malaria in an Area of Low Malaria Endemicity, PLOS PATHOGENS, Vol: 7, ISSN: 1553-7366
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- Citations: 41
Griffin JT, Hollingsworth D, Okell LC, et al., 2010, STRATEGIES TOWARDS <i>PLASMODIUM FALCIPARUM</i> MALARIA ELIMINATION IN AFRICA USING CURRENTLY AVAILABLE TOOLS, 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 262-262, ISSN: 0002-9637
Okell LC, Griffin J, Kleinschmidt I, et al., 2010, REDUCTION OF MALARIA TRANSMISSION BY MASS TREATMENT: A COMPARISON OF OPERATIONAL STRATEGIES, 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 221-221, ISSN: 0002-9637
Horowitz A, Behrens RH, Okell L, et al., 2010, NK Cells as Effectors of Acquired Immune Responses: Effector CD4<SUP>+</SUP> T Cell-Dependent Activation of NK Cells Following Vaccination, JOURNAL OF IMMUNOLOGY, Vol: 185, Pages: 2808-2818, ISSN: 0022-1767
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- Citations: 133
de Souza JB, Runglall M, Corran PH, et al., 2010, Neutralization of Malaria Glycosylphosphatidylinositol <i>In Vitro</i> by Serum IgG from Malaria-Exposed Individuals, INFECTION AND IMMUNITY, Vol: 78, Pages: 3920-3929, ISSN: 0019-9567
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- Citations: 8
Griffin JT, Hollingsworth TD, Okell LC, et al., 2010, Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies., PLoS Med, Vol: 7, Pages: 1-27, ISSN: 1549-1676
BACKGROUND: Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. METHODS AND FINDINGS: We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained. In two of the moderate-transmission settings (EIR approximately 43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR approximately 586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or
Bousema T, Okell L, Shekalaghe S, et al., 2010, Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs, Malaria Journal, Vol: 9, ISSN: 1475-2875
BACKGROUND: There is renewed acknowledgement that targeting gametocytes is essential for malaria control and elimination efforts. Simple mathematical models were fitted to data from clinical trials in order to determine the mean gametocyte circulation time and duration of gametocyte carriage in treated malaria patients. METHODS: Data were used from clinical trials from East Africa. The first trial compared non-artemisinin combination therapy (non-ACT: sulphadoxine-pyrimethamine (SP) plus amodiaquine) and artemisinin-based combination therapy (ACT: SP plus artesunate (AS) or artemether-lumefantrine). The second trial compared ACT (SP+AS) with ACT in combination with a single dose of primaquine (ACT-PQ: SP+AS+PQ). Mature gametocytes were quantified in peripheral blood samples by nucleic acid sequence based amplification. A simple deterministic compartmental model was fitted to gametocyte densities to estimate the circulation time per gametocyte; a similar model was fitted to gametocyte prevalences to estimate the duration of gametocyte carriage after efficacious treatment. RESULTS: The mean circulation time of gametocytes was 4.6-6.5 days. After non-ACT treatment, patients were estimated to carry gametocytes for an average of 55 days (95% CI 28.7 - 107.7). ACT reduced the duration of gametocyte carriage fourfold to 13.4 days (95% CI 10.2-17.5). Addition of PQ to ACT resulted in a further fourfold reduction of the duration of gametocyte carriage. CONCLUSIONS: These findings confirm previous estimates of the circulation time of gametocytes, but indicate a much longer duration of (low density) gametocyte carriage after apparently successful clearance of asexual parasites. ACT shortened the period of gametocyte carriage considerably, and had the most pronounced effect on mature gametocytes when combined with PQ.
Steenkeste N, Rogers WO, Okell L, et al., 2010, Sub-microscopic malaria cases and mixed malaria infection in a remote area of high malaria endemicity in Rattanakiri province, Cambodia: implication for malaria elimination, Malaria Journal, Vol: 9, Pages: 108-108, ISSN: 1475-2875
BACKGROUND: Malaria microscopy and rapid diagnostic tests are insensitive for very low-density parasitaemia. This insensitivity may lead to missed asymptomatic sub-microscopic parasitaemia, a potential reservoir for infection. Similarly, mixed infections and interactions between Plasmodium species may be missed. The objectives were first to develop a rapid and sensitive PCR-based diagnostic method to detect low parasitaemia and mixed infections, and then to investigate the epidemiological importance of sub-microscopic and mixed infections in Rattanakiri Province, Cambodia. METHODS: A new malaria diagnostic method, using restriction fragment length polymorphism analysis of the cytochrome b genes of the four human Plasmodium species and denaturing high performance liquid chromatography, has been developed. The results of this RFLP-dHPLC method have been compared to 1) traditional nested PCR amplification of the 18S rRNA gene, 2) sequencing of the amplified fragments of the cytochrome b gene and 3) microscopy. Blood spots on filter paper and Giemsa-stained blood thick smears collected in 2001 from 1,356 inhabitants of eight villages of Rattanakiri Province have been analysed by the RFLP-dHPLC method and microscopy to assess the prevalence of sub-microscopic and mixed infections. RESULTS: The sensitivity and specificity of the new RFLP-dHPLC was similar to that of the other molecular methods. The RFLP-dHPLC method was more sensitive and specific than microscopy, particularly for detecting low-level parasitaemia and mixed infections. In Rattanakiri Province, the prevalences of Plasmodium falciparum and Plasmodium vivax were approximately two-fold and three-fold higher, respectively, by RFLP-dHPLC (59% and 15%, respectively) than by microscopy (28% and 5%, respectively). In addition, Plasmodium ovale and Plasmodium malariae were never detected by microscopy, while they were detected by RFLP-dHPLC, in 11.2% and 1.3% of the blood samples, respectively. Moreover, the proport
Wipasa J, Suphavilai C, Okell LC, et al., 2010, Long-lived antibody and B Cell memory responses to the human malaria parasites, Plasmodium falciparum and Plasmodium vivax, PLoS Pathog, Vol: 6, ISSN: 1553-7374
Antibodies constitute a critical component of the naturally acquired immunity that develops following frequent exposure to malaria. However, specific antibody titres have been reported to decline rapidly in the absence of reinfection, supporting the widely perceived notion that malaria infections fail to induce durable immunological memory responses. Currently, direct evidence for the presence or absence of immune memory to malaria is limited. In this study, we analysed the longevity of both antibody and B cell memory responses to malaria antigens among individuals who were living in an area of extremely low malaria transmission in northern Thailand, and who were known either to be malaria naive or to have had a documented clinical attack of P. falciparum and/or P. vivax in the past 6 years. We found that exposure to malaria results in the generation of relatively avid antigen-specific antibodies and the establishment of populations of antigen-specific memory B cells in a significant proportion of malaria-exposed individuals. Both antibody and memory B cell responses to malaria antigens were stably maintained over time in the absence of reinfection. In a number of cases where antigen-specific antibodies were not detected in plasma, stable frequencies of antigen-specific memory B cells were nonetheless observed, suggesting that circulating memory B cells may be maintained independently of long-lived plasma cells. We conclude that infrequent malaria infections are capable of inducing long-lived antibody and memory B cell responses.
Okell LC, Ghani AC, Lyons E, et al., 2009, SUBMICROSCOPIC <i>PLASMODIUM FALCIPARUM</i> INFECTION IN ENDEMIC POPULATION SURVEYS: A SYSTEMATIC REVIEW AND META-ANALYSIS, 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 297-297, ISSN: 0002-9637
Corran P, Cook J, Okell L, et al., 2009, Serological methods for estimating transmission intensity
Okell LC, Ghani AC, Lyons E, et al., 2009, Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis, J Infect Dis, Vol: 200, Pages: 1509-1517, ISSN: 1537-6613
INTRODUCTION: Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. METHODS: We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy:PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. RESULTS: Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was >75% versus 12.0% when the prevalence determined by PCR was <10%). DISCUSSION: Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.
Okell L, Drakeley C, Bousema T, et al., 2008, MODELLING THE POTENTIAL IMPACT OF ARTEMISININ COMBINATION THERAPIES AND LONG-LASTING DRUG COMBINATIONS ON MALARIA TRANSMISSION INTENSITY: A CASE STUDY IN TANZANIA, 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 10-10, ISSN: 0002-9637
Drakeley C, Cook J, Corran P, et al., 2008, POTENTIAL CONTRIBUTION OF SERO-EPIDEMIOLOGICAL ANALYSIS FOR MALARIA ELIMINATION: HISTORICAL AND CURRENT PERSPECTIVES, 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 234-235, ISSN: 0002-9637
Kuh D, Mishra GD, Black S, et al., 2008, Offspring birth weight, gestational age and maternal characteristics in relation to glucose status at age 53 years: evidence from a national birth cohort, DIABETIC MEDICINE, Vol: 25, Pages: 530-535, ISSN: 0742-3071
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- Citations: 8
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