Publications
131 results found
Basanez M, Lamberton PHL, Cheke RA, et al., 2016, Onchocerciasis transmission in Ghana: the human blood index of sibling species of the Simulium damnosum complex, Parasites & Vectors, Vol: 9, ISSN: 1756-3305
BackgroundVector-biting behaviour is important for vector-borne disease (VBD) epidemiology. The proportion of blood meals taken on humans (the human blood index, HBI), is a component of the biting rate per vector on humans in VBD transmission models. Humans are the definitive host of Onchocerca volvulus, but the simuliid vectors feed on a range of animals and HBI is a key indicator of the potential for human onchocerciasis transmission. Ghana has a diversity of Simulium damnosum complex members, which are likely to vary in their HBIs, an important consideration for parameterization of onchocerciasis control and elimination models.MethodsHost-seeking and ovipositing S. damnosum (sensu lato) (s.l.) were collected from seven villages in four Ghanaian regions. Taxa were morphologically and molecularly identified. Blood meals from individually stored blackfly abdomens were used for DNA profiling, to identify previous host choice. Household, domestic animal, wild mammal and bird surveys were performed to estimate the density and diversity of potential blood hosts of blackflies.ResultsA total of 11,107 abdomens of simuliid females (which would have obtained blood meal(s) previously) were tested, with blood meals successfully amplified in 3,772 (34 %). A single-host species was identified in 2,857 (75.7 %) of the blood meals, of which 2,162 (75.7 %) were human. Simulium soubrense Beffa form, S. squamosum C and S. sanctipauli Pra form were the most anthropophagic (HBI = 0.92, 0.86 and 0.70, respectively); S. squamosum E, S. yahense and S. damnosum (sensu stricto) (s.s.)/S. sirbanum were the most zoophagic (HBI = 0.44, 0.53 and 0.63, respectively). The degree of anthropophagy decreased (but not statistically significantly) with increasing ratio of non-human/human blood hosts. Vector to human ratios ranged from 139 to 1,198 blackflies/person.ConclusionsDNA profiling can successfully identify blood meals from host-seeking and ovipositing blackflies.
Crellen T, Walker M, Cotton JA, et al., 2016, Reduced efficacy of praziquantel against Schistosoma mansoni is associated with multiple-rounds of mass drug administration, Clinical Infectious Diseases, Vol: 63, Pages: 1151-1159, ISSN: 1537-6591
The efficacy of praziquantel against Schistosoma mansoni was significantly lower in Ugandan schools that had received more prior rounds of mass drug administration, as determined by fitting a statistical model to parasite egg counts before and after treatment.
Bottomley C, Isham V, Vivas-Martínez S, et al., 2016, Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings, Parasites & Vectors, Vol: 9, ISSN: 1756-3305
BACKGROUND: The African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently the gold standard test for detecting patent Onchocerca volvulus infection, and the World Health Organization recommends their use to monitor progress of treatment programmes (but not to verify elimination). However, if they are used (in transition and in parallel to Ov-16 serology), sampling protocols should be designed to demonstrate that programmatic goals have been reached. The sensitivity of skin snips is key to the design of such protocols. METHODS: We develop a mathematical model for the number of microfilariae in a skin snip and parameterise it using data from Guatemala, Venezuela, Ghana and Cameroon collected before the start of ivermectin treatment programmes. We use the model to estimate sensitivity as a function of time since last treatment, number of snips taken, microfilarial aggregation and female worm fertility after exposure to 10 annual rounds of ivermectin treatment. RESULTS: The sensitivity of the skin snip method increases with time after treatment, with most of the increase occurring between 0 and 5 years. One year after the last treatment, the sensitivity of two skin snips taken from an individual infected with a single fertile female worm is 31 % if there is no permanent effect of multiple ivermectin treatments on fertility; 18 % if there is a 7 % reduction per treatment, and 0.6 % if there is a 35 % reduction. At 5 years, the corresponding sensitivities are 76 %, 62 % and 4.7 %. The sensitivity improves significantly if 4 skin snips are taken: in the absence of a permanent effect of ivermectin, the sensitivity of 4 skin snips is 53 % 1 year and 94 % 5 years after the last treatme
Frempong KK, Walker M, Cheke RA, et al., 2016, Does increasing treatment frequency address suboptimal responses to ivermectin for the control and elimination of river blindness?, Clinical Infectious Diseases, Vol: 62, Pages: 1338-1347, ISSN: 1537-6591
Background. Several African countries have adopted a biannual ivermectin distribution strategy in some foci to control and eliminate onchocerciasis. In 2010, the Ghana Health Service started biannual distribution to combat transmission hotspots and suboptimal responses to treatment. We assessed the epidemiological impact of the first 3 years of this strategy and quantified responses to ivermectin over 2 consecutive rounds of treatment in 10 sentinel communities.Methods. We evaluated Onchocerca volvulus community microfilarial intensity and prevalence in persons aged ≥20 years before the first, second, and fifth (or sixth) biannual treatment rounds using skin snip data from 956 participants. We used longitudinal regression modeling to estimate rates of microfilarial repopulation of the skin in a cohort of 217 participants who were followed up over the first 2 rounds of biannual treatment.Results. Biannual treatment has had a positive impact, with substantial reductions in infection intensity after 4 or 5 rounds in most communities. We identified 3 communities—all having been previously recognized as responding suboptimally to ivermectin—with statistically significantly high microfilarial repopulation rates. We did not find any clear association between microfilarial repopulation rate and the number of years of prior intervention, coverage, or the community level of infection.Conclusions. The strategy of biannual ivermectin treatment in Ghana has reduced O. volvulus microfilarial intensity and prevalence, but suboptimal responses to treatment remain evident in a number of previously and consistently implicated communities. Whether increasing the frequency of treatment will be sufficient to meet the World Health Organization's 2020 elimination goals remains uncertain.
Walker M, Mabud T, Olliaro PL, et al., 2016, New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel, Parasites & Vectors, Vol: 9, ISSN: 1756-3305
BACKGROUND:By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.METHODS:We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.RESULTS:We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.CONCLUSIONS:Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals.
Hollingsworth TD, Adams ER, Anderson RM, et al., 2015, Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases, Parasites & Vectors, Vol: 8, ISSN: 1756-3305
Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminatedisease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals forneglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyseswhich aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease,visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphaticfilariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: theimportance of epidemiological setting on the success of interventions; targeting groups who are at highest risk ofinfection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoirfor infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ whentrue elimination is not reached. The models elucidate the factors that may be contributing most to persistence ofdisease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall thiscollection presents new analyses to inform current control initiatives. These papers form a base from which furtherdevelopment of the models and more rigorous validation against a variety of datasets can help to give moredetailed advice. At the moment, the models’ predictions are being considered as the world prepares for a finalpush towards control or elimination of neglected tropical diseases by 2020.
Stolk WA, Walker M, Coffeng LE, et al., 2015, Required duration of mass ivermectin treatment for onchocerciasis elimination in Africa: a comparative modelling analysis, PARASITES & VECTORS, Vol: 8, ISSN: 1756-3305
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- Citations: 82
Deol AK, Basanez M-G, Walker M, et al., 2015, COMPARISON OF FULL AGE-INTENSITY PROFILES FOR SCHISTOSOMIASIS AND SOIL-TRANSMITTED HELMINTH INFECTION FROM A TWO-YEAR STUDY IN UGANDA, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 161-161, ISSN: 0002-9637
Deol AK, Webster JP, Harrison W, et al., 2015, Development of a Markov transition probability model to predict changes in schistosomiasis infection following treatment, TROPICAL MEDICINE & INTERNATIONAL HEALTH, Vol: 20, Pages: 237-237, ISSN: 1360-2276
Basanez MG, Turner HC, Walker M, et al., 2015, Human Onchocerciasis: Modelling the Potential Long-term Consequences of a Vaccination Programme, PLOS Neglected Tropical Diseases, Vol: 9, ISSN: 1935-2735
BackgroundCurrently, the predominant onchocerciasis control strategy in Africa is annual mass drugadministration (MDA) with ivermectin. However, there is a consensus among the globalhealth community, supported by mathematical modelling, that onchocerciasis in Africa willnot be eliminated within proposed time frameworks in all endemic foci with only annualMDA, and novel and alternative strategies are urgently needed. Furthermore, use of MDAwith ivermectin is already compromised in large areas of central Africa co-endemic with Loaloa, and there are areas where suboptimal or atypical responses to ivermectin have beendocumented. An onchocerciasis vaccine would be highly advantageous in these areas.Methodology/Principal FindingsWe used a previously developed onchocerciasis transmission model (EPIONCHO) toinvestigate the impact of vaccination in areas where loiasis and onchocerciasis are coendemicand ivermectin is contraindicated. We also explore the potential influence of a vaccinationprogramme on infection resurgence in areas where local elimination has been successfullyachieved. Based on the age range included in the Expanded Programme onImmunization (EPI), the vaccine was assumed to target 1 to 5 year olds. Our modellingresults indicate that the deployment of an onchocerciasis vaccine would have a beneficialimpact in onchocerciasis–loiasis co-endemic areas, markedly reducing microfilarial load inthe young (under 20 yr) age groups.Conclusions/SignificanceAn onchocerciasis prophylactic vaccine would reduce the onchocerciasis disease burden inpopulations where ivermectin cannot be administered safely. Moreover, a vaccine could substantially decrease the chance of re-emergence of Onchocerca volvulus infection inareas where it is deemed that MDA with ivermectin can be stopped. Therefore, a vaccinewould protect the substantial investments made by present and past onchocerciasis controlprogrammes, decreasing the chance of disease recrudescence and offering an important
Lamberton PHL, Cheke RA, Winskill P, et al., 2015, Onchocerciasis Transmission in Ghana: Persistence under Different Control Strategies and the Role of the Simuliid Vectors, PLOS Neglected Tropical Diseases, Vol: 9, ISSN: 1935-2735
Walker M, Specht S, Churcher TS, et al., 2015, Therapeutic Efficacy and Macrofilaricidal Activity of Doxycycline for the Treatment of River Blindness, CLINICAL INFECTIOUS DISEASES, Vol: 60, Pages: 1199-1207, ISSN: 1058-4838
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- Citations: 68
Yalchin M, Oliveira A, Pencharz D, et al., 2015, Long-Term Survival Data in Progressing Advanced Midgut Neuroendocrine Tumours Following Peptide Receptor Radionuclide Therapy, 46th Annual Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S936-S936, ISSN: 0016-5085
Turner HC, Walker M, Attah SK, et al., 2015, The potential impact of moxidectin on onchocerciasis elimination in Africa: an economic evaluation based on the Phase II clinical trial data, Parasites & Vectors, Vol: 8, ISSN: 1756-3305
Walker M, Basanez M-G, Ouedraogo AL, et al., 2015, Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study, BMC BIOINFORMATICS, Vol: 16, ISSN: 1471-2105
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- Citations: 10
Toumpanakis C, Laskaratos F, Maragkoudakis E, et al., 2015, Predictive Factors for Antiproliferative Activity of Octreotide LAR in Advanced Neuroendocrine Tumors, 12th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Publisher: KARGER, Pages: 126-126, ISSN: 0028-3835
Yalchin M, Tharmalingam H, Owen C, et al., 2015, The Role of External Beam Radiotherapy in the Management of Advanced Neuroendocrine Tumors, 12th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Publisher: KARGER, Pages: 136-136, ISSN: 0028-3835
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- Citations: 3
Yalchin M, Oliveira A, Pencharz D, et al., 2015, Long-Term Follow-Up and Survival Data in Progressing Advanced Midgut Neuroendocrine Tumors Following Peptide Receptor Radionuclide Therapy, 12th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Publisher: KARGER, Pages: 133-133, ISSN: 0028-3835
Turner HC, Walker M, French MD, et al., 2014, Neglected tools for neglected diseases: mathematical models in economic evaluations, TRENDS IN PARASITOLOGY, Vol: 30, Pages: 562-570, ISSN: 1471-4922
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- Citations: 24
Lamberton PHL, Cheke RA, Walker M, et al., 2014, Onchocerciasis transmission in Ghana: biting and parous rates of host-seeking sibling species of the <i>Simulium damnosum</i> complex, PARASITES & VECTORS, Vol: 7, ISSN: 1756-3305
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- Citations: 26
Walker M, Churcher TS, Basanez M-G, 2014, Models for measuring anthelmintic drug efficacy for parasitologists, TRENDS IN PARASITOLOGY, Vol: 30, Pages: 528-537, ISSN: 1471-4922
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- Citations: 17
Turner HC, Walker M, Churcher TS, et al., 2014, Reaching the London Declaration on Neglected Tropical Diseases Goals for Onchocerciasis: An Economic Evaluation of Increasing the Frequency of Ivermectin Treatment in Africa, CLINICAL INFECTIOUS DISEASES, Vol: 59, Pages: 923-932, ISSN: 1058-4838
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- Citations: 69
Smyk DS, Alexander AK, Walker M, et al., 2014, Acute disseminated encephalomyelitis progressing to multiple sclerosis: Are infectious triggers involved?, IMMUNOLOGIC RESEARCH, Vol: 60, Pages: 16-22, ISSN: 0257-277X
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- Citations: 14
Turner HC, Walker M, Churcher TS, et al., 2014, Modelling the impact of ivermectin on River Blindness and its burden of morbidity and mortality in African Savannah: EpiOncho projections, PARASITES & VECTORS, Vol: 7, ISSN: 1756-3305
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- Citations: 49
Toumpanakis C, Laskaratos F, Maragkoudakis E, et al., 2014, Antiproliferative activity of octreotide LAR in advanced neuroendocrine tumors., 50th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Laskaratos F-M, Walker M, Walker M, et al., 2013, Predictive Factors for Early Mortality After Percutaneous Endoscopic and Radiologically-Inserted Gastrostomy, DIGESTIVE DISEASES AND SCIENCES, Vol: 58, Pages: 3558-3565, ISSN: 0163-2116
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- Citations: 32
Walker M, Winskill P, Basanez M-G, et al., 2013, Temporal and micro-spatial heterogeneity in the distribution of <i>Anopheles</i> vectors of malaria along the Kenyan coast, PARASITES & VECTORS, Vol: 6, ISSN: 1756-3305
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- Citations: 24
Turner HC, Osei-Atweneboana MY, Walker M, et al., 2013, The Cost of Annual versus Biannual Community-Directed Treatment of Onchocerciasis with Ivermectin: Ghana as a Case Study, PLOS NEGLECTED TROPICAL DISEASES, Vol: 7, ISSN: 1935-2735
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- Citations: 36
Churcher TS, Bousema T, Walker M, et al., 2013, Predicting mosquito infection from <i>Plasmodium falciparum</i> gametocyte density and estimating the reservoir of infection, ELIFE, Vol: 2, ISSN: 2050-084X
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- Citations: 142
Walker M, Hall A, Basáñez M-G, 2013, Ascaris lumbricoides: New Epidemiological Insights and Mathematical Approaches, Ascaris: The Neglected Parasite, Editors: Holland, Publisher: Newnes, Pages: 155-201, ISBN: 9780123972859
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