Imperial College London

DrMartinWalker

Faculty of MedicineSchool of Public Health

Honorary Lecturer in Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3229m.walker06 CV

 
 
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Location

 

G2716 South Wharf RoadSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

104 results found

Fall CB, Lambert S, Leger E, Yasenev L, Garba AD, Diop SD, Borlase A, Catalano S, Faye B, Walker M, Sene M, Webster JPet al., 2021, Hybridized zoonotic schistosoma infections result in hybridized morbidity profiles: a clinical morbidity study amongst co-infected human populations of Senegal, Microorganisms, Vol: 9, Pages: 1-18, ISSN: 2076-2607

Hybridization of infectious agents is a major emerging public and veterinary health concern at the interface of evolution, epidemiology, and control. Whilst evidence of the extent of hybridization amongst parasites is increasing, their impact on morbidity remains largely unknown. This may be predicted to be particularly pertinent where parasites of animals with contrasting pathogenicity viably hybridize with human parasites. Recent research has revealed that viable zoonotic hybrids between human urogenital Schistosoma haematobium with intestinal Schistosoma species of livestock, notably Schistosoma bovis, can be highly prevalent across Africa and beyond. Examining human populations in Senegal, we found increased hepatic but decreased urogenital morbidity, and reduced improvement following treatment with praziquantel, in those infected with zoonotic hybrids compared to non-hybrids. Our results have implications for effective monitoring and evaluation of control programmes, and demonstrate for the first time the potential impact of parasite hybridizations on host morbidity.

Journal article

Jewell PD, Abraham A, Schmidt V, Buell KG, Bustos JA, Garcia HH, Dixon MA, Walker M, Ngowi BJ, Basáñez M-G, Winkler ASet al., 2021, Neurocysticercosis and HIV/AIDS Co-infection: A Scoping Review., Tropical Medicine and International Health, ISSN: 1360-2276

OBJECTIVES: Neurocysticercosis (NCC) and human immunodeficiency virus (HIV) have high disease burden and are prevalent in overlapping low- and middle-income areas. Yet, treatment guidance for people living with HIV/AIDS (PLWH/A) co-infected with NCC is currently lacking. This study aims to scope the available literature on HIV/AIDS and NCC co-infection, focusing on epidemiology, clinical characteristics, diagnostics, and treatment outcomes. METHODS: The scoping literature review methodological framework, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of 16,969 records identified through database searching and 45 additional records from other sources were reduced to 52 included studies after a standardised selection process. RESULTS: Two experimental studies, ten observational studies, 23 case series/case reports and 17 reviews or letters were identified. Observational studies demonstrated similar NCC seroprevalence in PLWH/A and their HIV-negative counterparts. Of 29 PLWH/A and NCC co-infection, 17 (59%) suffered from epileptic seizures, 15 (52%) from headaches, and 15 (52%) had focal neurological deficits. Eighteen (62%) had viable vesicular cysts and six (21%) had calcified cysts. Fifteen (52%) were treated with albendazole, of which 11 (73%) responded well to treatment. Five individuals potentially demonstrated an immune-reconstitution inflammatory syndrome after commencing anti-retroviral therapy, although this was in the absence of immunological and neuroimaging confirmation. CONCLUSIONS: There is a paucity of evidence to guide treatment of PLWH/A and NCC co-infection. There is a pressing need for high-quality studies in this patient group to appropriately inform diagnostic and management guidelines for HIV-positive patients with NCC.

Journal article

Stolk WA, Blok DJ, Hamley JID, Cantey PT, de Vlas SJ, Walker M, Basáñez M-Get al., 2021, Scaling-down mass ivermectin treatment for onchocerciasis elimination: modelling the impact of the geographical unit for decision making, Clinical Infectious Diseases, Vol: 72, Pages: S165-S171, ISSN: 1058-4838

BACKGROUND: Due to spatial heterogeneity in onchocerciasis transmission, the duration of ivermectin mass drug administration (MDA) required for eliminating onchocerciasis will vary within endemic areas and the occurrence of transmission 'hotspots' is inevitable. The geographical scale at which stop-MDA decisions are made will be a key driver in how rapidly national programmes can scale down active intervention upon achieving the epidemiological targets for elimination. METHODS: We use two onchocerciasis models (EPIONCHO-IBM and ONCHOSIM) to predict the likelihood of achieving elimination by 2030 in Africa, accounting for variation in pre-intervention endemicity levels and histories of ivermectin treatment. We explore how decision-making at contrasting geographical scales (community vs. larger scale 'project') changes projections on populations still requiring MDA or transitioning to post-treatment surveillance. RESULTS: The total population considered grows from 118 million people in 2020 to 136 million in 2030. If stop-MDA decisions are made at project level, the number of people requiring treatment declines from 69-118 million in 2020 to 59-118 million in 2030. If stop-MDA decisions are made at community level, the numbers decline from 23-81 million in 2020 to 15-63 million in 2030. The lower estimates in these predictions intervals are based on ONCHOSIM, the upper limits on EPIONCHO-IBM. DISCUSSION/CONCLUSIONS: The geographical scale at which stop-MDA decisions are made strongly determines how rapidly national onchocerciasis programmes can scale down MDA programmes. Stopping in portions of project areas or transmission zones would free up human and economic resources.

Journal article

Dolo H, Coulibaly YI, Sow M, Dembélé M, Doumbia SS, Coulibaly SY, Sangare MB, Dicko I, Diallo AA, Soumaoro L, Coulibaly ME, Diarra D, Colebunders R, Nutman TB, Walker M, Basáñez M-Get al., 2021, Serological evaluation of onchocerciasis and lymphatic filariasis elimination in the Bakoye and Falémé Foci, Mali, Clinical Infectious Diseases, Vol: 72, Pages: 1585-1593, ISSN: 1058-4838

BACKGROUND: In Mali, ivermectin-based onchocerciasis elimination from the Bakoye and Falémé foci, reported in 2009-2012, was a beacon leading to policy shifting from morbidity control to elimination of transmission (EOT). These foci are also endemic for lymphatic filariasis (LF). In 2007-2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24-25 years of treatment to evaluate if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved. METHODS: The SD Bioline Onchocerciasis/LF IgG4 biplex rapid diagnostic test (RDT) was used in 2,186 children aged 3-10 years in 13 villages (plus two hamlets) in Bakoye, and 2,270 children in 15 villages (plus one hamlet) in Falémé. In Bakoye, all-age serosurveys were conducted in three historically hyperendemic villages, testing 1,867 individuals aged 3-78 years. RESULTS: In Bakoye, IgG4 seropositivity was 0.27% (95%CI=0.13-0.60%) for both Ov16 and Wb123 antigens. In Falémé, Ov16 and Wb123 seroprevalence was, respectively, 0.04% (95%CI=0.01-0.25%) and 0.09% (95%CI=0.02-0.32%). Ov16-seropositive children were from historically meso- and hyperendemic villages. Ov16 positivity was <2% in those ≤14 years, increasing to 16% in those ≥40 years. Wb123 seropositivity was <2% in those ≤39 years, reaching 3% in those ≥40 years. CONCLUSIONS: Notwithstanding uncertainty in the biplex RDT sensitivity, Ov16 and Wb123 seroprevalence among children in Bakoye and Falémé appears consistent with EOT (onchocerciasis) and EPHP (LF) since stopping treatment in 2016. The few Ov16-seropositive children should be skin-snip PCR tested and followed up.

Journal article

Neves MI, Gower CM, Webster JP, Walker Met al., 2021, Revisiting density-dependent fecundity in schistosomes using sibship reconstruction., PLoS Neglected Tropical Diseases, Vol: 15, Pages: 1-16, ISSN: 1935-2727

The stability of parasite populations is regulated by density-dependent processes occurring at different stages of their life cycle. In dioecious helminth infections, density-dependent fecundity is one such regulatory process that describes the reduction in egg production by female worms in high worm burden within-host environments. In human schistosomiasis, the operation of density-dependent fecundity is equivocal and investigation is hampered by the inaccessibility of adult worms that are located intravascularly. Current understanding is almost exclusively limited to data collected from two human autopsy studies conducted over 40 years ago, with subsequent analyses having reached conflicting conclusions. Whether egg production is regulated in a density-dependent manner is key to predicting the effectiveness of interventions targeting the elimination of schistosomiasis and to the interpretation of parasitological data collected during monitoring and evaluation activities. Here, we revisit density-dependent fecundity in the two most globally important human Schistosoma spp. using a statistical modelling approach that combines molecular inference on the number of parents/adult worms in individual human hosts with parasitological egg count data from mainland Tanzania and Zanzibar. We find a non-proportional relationship between S. haematobium egg counts and inferred numbers of female worms, providing the first clear evidence of density-dependent fecundity in this schistosome species. We do not find robust evidence for density-dependent fecundity in S. mansoni because of high sensitivity to some modelling assumptions and the lower statistical power of the available data. We discuss the strengths and limitations of our model-based analytical approach and its potential for improving our understanding of density dependence in schistosomiasis and other human helminthiases earmarked for elimination.

Journal article

Walker M, Hamley J, Milton P, Kinrade S, Monnot F, Specht S, Pedrique B, Basanez M-Get al., 2021, Supporting drug development for neglected tropical diseases using mathematical modelling, Clinical Infectious Diseases, ISSN: 1058-4838

Drug-based interventions are at the heart of global efforts to reach elimination as a public health problem (trachoma, soil-transmitted helminthiases, schistosomiasis, lymphatic filariasis) or elimination of transmission (onchocerciasis) for five of the most prevalent neglected tropical diseases tackled via the World Health Organization preventive chemotherapy strategy. While for some of these diseases there is optimism that currently available drugs will be sufficient to achieve the proposed elimination goals, for others—particularly onchocerciasis—there is a growing consensus that novel therapeutic options will be needed. Since in this area no high return of investment is possible, minimizing wasted money and resources is essential. Here, we use illustrative results to show how mathematical modelling can guide the drug development pathway, yielding resource-saving and efficiency payoffs, from the refinement of target product profiles and intended context of use, to the design of clinical trials.

Journal article

Toor J, Adams ER, Aliee M, Amoah B, Anderson RM, Ayabina D, Bailey R, Basáñez M-G, Blok DJ, Blumberg S, Borlase A, Rivera RC, Castaño MS, Chitnis N, Coffeng LE, Crump RE, Das A, Davis CN, Davis EL, Deiner MS, Diggle PJ, Fronterre C, Giardina F, Giorgi E, Graham M, Hamley JID, Huang C-I, Kura K, Lietman TM, Lucas TCD, Malizia V, Medley GF, Meeyai A, Michael E, Porco TC, Prada JM, Rock KS, Le Rutte EA, Smith ME, Spencer SEF, Stolk WA, Touloupou P, Vasconcelos A, Vegvari C, de Vlas SJ, Walker M, Hollingsworth TDet al., 2021, Predicted impact of COVID-19 on neglected tropical disease programs and the opportunity for innovation, Clinical Infectious Diseases, Vol: 72, Pages: 1463-1466, ISSN: 1058-4838

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.

Journal article

Hamley JID, Blok DJ, Walker M, Milton P, Hopkins AD, Hamill LC, Downs P, de Vlas SJ, Stolk WA, Basáñez M-Get al., 2021, What does the COVID-19 pandemic mean for the next decade of onchocerciasis control and elimination?, Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol: 115, Pages: 269-280, ISSN: 0035-9203

BACKGROUND: Mass drug administration (MDA) of ivermectin for onchocerciasis has been disrupted by the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modelling can help predict how missed/delayed MDA will affect short-term epidemiological trends and elimination prospects by 2030. METHODS: Two onchocerciasis transmission models (EPIONCHO-IBM and ONCHOSIM) are used to simulate microfilarial prevalence trends, elimination probabilities and age profiles of Onchocerca volvulus microfilarial prevalence and intensity for different treatment histories and transmission settings, assuming no interruption, a 1-y (2020) interruption or a 2-y (2020-2021) interruption. Biannual MDA or increased coverage upon MDA resumption are investigated as remedial strategies. RESULTS: Programmes with shorter MDA histories and settings with high pre-intervention endemicity will be the most affected. Biannual MDA is more effective than increasing coverage for mitigating COVID-19's impact on MDA. Programmes that had already switched to biannual MDA should be minimally affected. In high-transmission settings with short treatment history, a 2-y interruption could lead to increased microfilarial load in children (EPIONCHO-IBM) and adults (ONCHOSIM). CONCLUSIONS: Programmes with shorter (annual MDA) treatment histories should be prioritised for remedial biannual MDA. Increases in microfilarial load could have short- and long-term morbidity and mortality repercussions. These results can guide decision-making to mitigate the impact of COVID-19 on onchocerciasis elimination.

Journal article

Cheke RA, Little KE, Young S, Walker M, Basáñez M-Get al., 2021, Taking the strain out of onchocerciasis? A reanalysis of blindness and transmission data does not support the existence of a savannah blinding strain of onchocerciasis in West Africa., Pages: 1-50

Onchocerciasis (also known as 'river blindness'), is a neglected tropical disease (NTD) caused by the (Simulium-transmitted) filarial nematode Onchocerca volvulus. The occurrence of 'blinding' (savannah) and non-blinding (forest) parasite strains and the existence of corresponding, locally adapted Onchocerca-Simulium complexes were postulated to explain greater blindness prevalence in savannah than in forest foci. As a result, the World Health Organization (WHO) Onchocerciasis Control Programme in West Africa (OCP) focused anti-vectorial and anti-parasitic interventions in savannah endemic areas. In this paper, village-level data on blindness prevalence, microfilarial prevalence, and transmission intensity (measured by the annual transmission potential, the number of infective, L3, larvae per person per year) were extracted from 16 West-Central Africa-based publications, and analysed according to habitat (forest, forest-savannah mosaic, savannah) to test the dichotomous strain hypothesis in relation to blindness. When adjusting for sample size, there were no statistically significant differences in blindness prevalence between the habitats (one-way ANOVA, P=0.68, mean prevalence for forest=1.76±0.37 (SE); mosaic=1.49±0.38; savannah=1.89±0.26). The well-known relationship between blindness prevalence and annual transmission potential for savannah habitats was confirmed and shown to hold for (but not to be statistically different from) forest foci (excluding data from southern Côte d'Ivoire, in which blindness prevalence was significantly lower than in other West African forest communities, but which had been the focus of studies leading to the strain-blindness hypothesis that was accepted by OCP planners). We conclude that the evidence for a savannah blinding onchocerciasis strain in simple contrast with a non-blinding forest strain is equivocal. A re-appraisal of the strain hypothesis to explain patterns of ocular disease is needed to impr

Book chapter

Dolo H, Coulibaly YI, Sow M, Dembele M, Doumbia SS, Coulibaly SY, Sangare MB, Dicko I, Diallo AA, Soumaoro L, Coulibaly ME, Colebunders R, Nutman TB, Walker M, Basanez M-Get al., 2020, Serological evaluation of onchocerciasis and lymphatic filariasis elimination in the Bakoye and Faleme foci, Mali, Publisher: ELSEVIER SCI LTD, Pages: 427-428, ISSN: 1201-9712

Conference paper

Milne G, Webster JP, Walker M, 2020, Toxoplasma gondii: An Underestimated Threat?, TRENDS IN PARASITOLOGY, Vol: 36, Pages: 959-969, ISSN: 1471-4922

Journal article

Milne G, Webster JP, Walker M, 2020, Towards improving interventions against toxoplasmosis by identifying routes of transmission using sporozoite-specific serological tools., Clinical Infectious Diseases, Vol: 71, Pages: e686-e693, ISSN: 1058-4838

BACKGROUND: Horizontal transmission of Toxoplasma gondii occurs primarily via ingestion of environmental oocysts or consumption of undercooked/raw meat containing cyst-stage bradyzoites. The relative importance of these two transmission routes remains unclear. Oocyst infection can be distinguished from bradyzoite infection by identification of IgG antibodies against T. gondii-embryogenesis-related protein (TgERP). These antibodies are, however, thought to persist for only 6-8 months in human sera, limiting the use of TgERP serology to only those patients recently exposed to T. gondii. Yet recent serological survey data indicate a more sustained persistence of anti-TgERP antibodies. Elucidating the duration of anti-TgERP IgG will help to determine whether TgERP serology has epidemiological utility for quantifying the relative importance of different routes of T. gondii transmission. METHODS: We developed a sero-catalytic mathematical model to capture the change in seroprevalence of non-stage-specific IgG and anti-TgERP IgG antibodies with human age. The model was fitted to published datasets collected in an endemic region of Brazil to estimate the duration of anti-TgERP IgG antibodies, accounting for variable age-force of infection profiles and uncertainty in the diagnostic performance of TgERP serology. RESULTS: We found that anti-TgERP IgG persists for substantially longer than previously recognised, with estimates ranging from 8.3 to 41.1 years. The Brazilian datasets were consistent with oocysts being the predominant transmission route in these settings. CONCLUSIONS: The longer than previously recognised duration of anti-TgERP antibodies indicates that anti-TgERP serology could be a useful tool for delineating T. gondii transmission routes in human populations. TgERP serology may therefore be an important epidemiological tool for informing the design of tailored, setting-specific public health information campaigns and interventions.

Journal article

Dixon MA, Winskill P, Harrison W, Whittaker C, Schmidt V, Sarti E, Bawm S, Dione MM, Thomas LF, Walker M, Basanez M-Get al., 2020, Force-of-Infection of Taenia solium porcine cysticercosis: a modelling analysis to assess global incidence and prevalence trends, Scientific Reports, Vol: 10, ISSN: 2045-2322

The World Health Organization (WHO) called, in 2012, for a validated strategy towards Taenia solium taeniasis/cysticercosis control and elimination. Estimating pig force-of-infection (FoI, the average rate at which susceptible pigs become infected) across geographical settings will help understand local epidemiology and inform effective intervention design. Porcine cysticercosis (PCC) age-prevalence data (from 15 studies in Latin America, Africa and Asia) were identified through systematic review. Catalytic models were fitted to the data using Bayesian methods, incorporating uncertainty in diagnostic performance, to estimate rates of antibody seroconversion, viable metacestode acquisition, and seroreversion/infection loss. There was evidence of antibody seroreversion across 5 studies, and of infection loss in 6 studies measured by antigen or necropsy, indicating transient serological responses and natural resolution of infection. Concerted efforts should be made to collect robust data using improved diagnostics to better understand geographical heterogeneities in T. solium transmission to support post-2020 WHO targets.

Journal article

Milne G, Fujimoto C, Bean T, Peters HJ, Hemmington M, Taylor C, Fowkes RC, Martineau HM, Hamilton CM, Walker M, Mitchell JA, Leger E, Priestnall SL, Webster JPet al., 2020, Infectious causation of abnormal host behavior: toxoplasma gondiiand Its potential association with dopey fox syndrome, Frontiers in Psychiatry, Vol: 11, Pages: 1-16, ISSN: 1664-0640

The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, can infect all warm-blooded animals. T. gondii can subtly alter host behaviors—either through manipulation to enhance transmission to the feline definitive host or as a side-effect, or “constraint,” of infection. In humans, T. gondii infection, either alone or in association with other co-infecting neurotropic agents, has been reliably associated with both subtle behavioral changes and, in some cases, severe neuropsychiatric disorders, including schizophrenia. Research on the potential impact of T. gondii on the behavior of other long-lived naturally infected hosts is lacking. Recent studies reported a large number of wild red foxes exhibiting a range of aberrant behavioral traits, subsequently classified as Dopey Fox Syndrome (DFS). Here we assessed the potential association between T. gondii and/or other neurotropic agents with DFS. Live, captive foxes within welfare centers were serologically tested for T. gondii and, if they died naturally, PCR-tested for vulpine circovirus (FoxCV). Post-mortem pseudo-control wild foxes, obtained from pest management companies, were PCR-tested for T. gondii, FoxCV, canine distemper virus (CDV), canine adenovirus type (CAV)-1 and CAV-2. We also assessed, using non-invasive assays, whether T. gondii–infected foxes showed subtle behavioral alterations as observed among infected rodent (and other) hosts, including altered activity, risk, and stress levels. All foxes tested negative for CAV, CDV, CHV, and DogCV. DFS was found to be associated with singular T. gondii infection (captives vs. pseudo-controls, 33.3% (3/9) vs. 6.8% (5/74)) and singular FoxCV infection (66.7% (6/9) vs. 11.1% (1/9)) and with T. gondii/FoxCV co-infection (33.3% (3/9) vs. 11.1% (1/9)). Overall, a higher proportion of captive foxes had signs of neuroinflammation compared to pseudo-controls (66.7% (4/6) vs. 11.1% (1/9)). Consistent with behavioral changes

Journal article

Basanez M-G, Milton P, Hamley J, Walker Met al., 2020, Moxidectin: an oral treatment for human onchocerciasis, Expert Review of Anti-infective Therapy, Vol: 18, Pages: 1067-1081, ISSN: 1478-7210

Introduction: Moxidectin is a milbemycin endectocide recently approved for the treatment of humanonchocerciasis. Onchocerciasis, earmarked for elimination of transmission, is a filarial infection endemicin Africa, Yemen, and the Amazonian focus straddling Venezuela and Brazil. Concerns over whether thepredominant treatment strategy (yearly mass drug administration (MDA) of ivermectin) is sufficient toachieve elimination in all endemic foci have refocussed attention upon alternative treatments.Moxidectin’s stronger and longer microfilarial suppression compared to ivermectin in both phase IIand III clinical trials indicates its potential as a novel powerful drug for onchocerciasis elimination.Areas covered: This work summarizes the chemistry and pharmacology of moxidectin, reviews thephase II and III clinical trials evidence on tolerability, safety, and efficacy of moxidectin versus ivermectin, and discusses the implications of moxidectin’s current regulatory status.Expert opinion: Moxidectin’s superior clinical performance has the potential to substantially reducetimes to elimination compared to ivermectin. If donated, moxidectin could mitigate the additionalprogrammatic costs of biannual ivermectin distribution because, unlike other alternatives, it can use theexisting community-directed treatment infrastructure. A pediatric indication (for children <12 years) anddetermination of its usefulness in onchocerciasis–loiasis co-endemic areas will greatly help fulfill thepotential of moxidectin for the treatment and elimination of onchocerciasis.

Journal article

Webster JP, Neves MI, Webster BL, Pennance T, Rabone M, Gouvras AN, Allan F, Walker M, Rollinson Det al., 2020, Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 103, Pages: 80-91, ISSN: 0002-9637

Journal article

Hamley J, Walker M, Coffeng LE, Milton P, de Vlas SJ, Stolk WA, Basanez M-Get al., 2020, Structural uncertainty in onchocerciasis transmission models influences the estimation of elimination thresholds and selection of age groups for seromonitoring, Journal of Infectious Diseases, Vol: 221, Pages: S510-S518, ISSN: 0022-1899

Background. The World Health Organization recommends monitoring Ov16 serologyin children aged <10 years for stopping mass ivermectin administration. Transmission models can help to identify the most informative age groups for serological monitoring and investigate the discriminatory power of serology-based elimination thresholds.Model predictions will depend on assumed age-exposure patterns and transmission efficiency at low infection levels. Methods. The individual-based transmission model, EPIONCHO-IBM, was used toassess: i) the most informative age groups for serological monitoring using receiveroperator characteristic curves for different elimination thresholds under various age-dependent exposure assumptions, including those of ONCHOSIM (another widely-used model), and ii) the influence of within-human density-dependent parasite establishment (included in EPIONCHO-IBM but not in ONCHOSIM) on positive predictive values for different serological thresholds.Results. When assuming EPIONCHO-IBM exposure patterns, under-10s are themost informative age group for seromonitoring; when assuming ONCHOSIM’s exposure patterns, 5–15-year olds are the most informative (as published elsewhere).Omitting density-dependent parasite establishment results in more lenientseroprevalence thresholds, even for higher baseline infection prevalence and shorter treatment durations.Conclusions. Selecting appropriate seromonitoring age groups depends critically onage-dependent exposure patterns. The role of density dependence on elimination thresholds largely explains differing EPIONCHO-IBM and ONCHOSIM elimination predictions.

Journal article

Walker M, Hamley JID, Milton P, Monnot F, Pedrique B, Basáñez M-Get al., 2020, Designing antifilarial drug trials using clinical trial simulators, Nature Communications, Vol: 11, Pages: 1-11, ISSN: 2041-1723

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.

Journal article

Behrend M, Basanez M-G, Hamley JID, Porco TC, Stolk WA, Walker M, de Vlas SJet al., 2020, Modelling for policy: the five principles of the Neglected Tropical Diseases Modelling Consortium, PLoS Neglected Tropical Diseases, ISSN: 1935-2727

Journal article

Nana Djeunga H, Domche A, Niamsi-Emalio Y, Moungui H, Walker M, Kamgno J, Basanez M-Get al., 2020, Situation analysis of onchocerciasis in Cameroon: a protocol for systematic review of epidemiological studies and impact of disease control interventions, Systematic Reviews, ISSN: 2046-4053

Journal article

Dixon M, Braae UC, Winskill P, Devleesschauwer B, Trevisan C, Van Damme I, Walker M, Hamley JID, Ramiandrasoa SN, Schmidt V, Gabriël S, Harrison W, Basanez M-Get al., 2020, Modelling for Taenia solium control strategies beyond 2020, Bulletin of the World Health Organization, Vol: 98, Pages: 198-205, ISSN: 0042-9686

The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. soliumtransmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies.

Journal article

Deol AK, Fleming FM, Calvo-Urbano B, Walker M, Bucumi V, Gnandou I, Tukahebwa EM, Jemu S, Mwingira UJ, Alkohlani A, Traore M, Ruberanziza E, Toure S, Basanez M-G, French MD, Webster JPet al., 2019, Schistosomiasis — assessing progress toward the 2020 and 2025 global goals, New England Journal of Medicine, Vol: 381, Pages: 2519-2528, ISSN: 0028-4793

BackgroundWith the vision of “a world free of schistosomiasis,” the World Health Organization (WHO) set ambitious goals of control of this debilitating disease and its elimination as a public health problem by 2020 and 2025, respectively. As these milestones become imminent, and if programs are to succeed, it is important to evaluate the WHO programmatic guidelines empirically.MethodsWe collated and analyzed multiyear cross-sectional data from nine national schistosomiasis control programs (in eight countries in sub-Saharan Africa and in Yemen). Data were analyzed according to schistosome species (Schistosoma mansoni or S. haematobium), number of treatment rounds, overall prevalence, and prevalence of heavy-intensity infection. Disease control was defined as a prevalence of heavy-intensity infection of less than 5% aggregated across sentinel sites, and the elimination target was defined as a prevalence of heavy-intensity infection of less than 1% in all sentinel sites. Heavy-intensity infection was defined as at least 400 eggs per gram of feces for S. mansoni infection or as more than 50 eggs per 10 ml of urine for S. haematobium infection.ResultsAll but one country program (Niger) reached the disease-control target by two treatment rounds or less, which is earlier than projected by current WHO guidelines (5 to 10 years). Programs in areas with low endemicity levels at baseline were more likely to reach both the control and elimination targets than were programs in areas with moderate and high endemicity levels at baseline, although the elimination target was reached only for S. mansoni infection (in Burkina Faso, Burundi, and Rwanda within three treatment rounds). Intracountry variation was evident in the relationships between overall prevalence and heavy-intensity infection (stratified according to treatment rounds), a finding that highlights the challenges of using one metric to define control or elimination across all epidemiologic settings.Conclusio

Journal article

Hamley JID, Milton P, Walker M, Basáñez M-Get al., 2019, Modelling exposure heterogeneity and density dependence in onchocerciasis using a novel individual-based transmission model, EPIONCHO-IBM: Implications for elimination and data needs, PLoS Neglected Tropical Diseases, Vol: 13, Pages: e0007557-e0007557, ISSN: 1935-2727

BackgroundDensity dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin.Methodology/Principal findingsDensity dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d’Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model.Conclusions/SignificanceThis is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improvin

Journal article

Buell KG, Whittaker C, Chesnais CB, Jewell PD, Pion SDS, Walker M, Basáñez M-G, Boussinesq Met al., 2019, Atypical clinical manifestations of Loiasis and their relevance for endemic populations, Open Forum Infectious Diseases, Vol: 6, ISSN: 2328-8957

Background: Loiasis is mostly considered a relatively benign infection when compared with other filarial and parasitic diseases, with Calabar swellings and eyeworm being the most common signs. Yet, there are numerous reports in the literature of more serious sequelae. Establishing the relationship between infection and disease is a crucial first step toward estimating the burden of loiasis. Methods: We conducted a systematic review of case reports containing 329 individuals and detailing clinical manifestations of loiasis with a focus on nonclassical, atypical presentations. Results: Results indicate a high proportion (47%) of atypical presentations in the case reports identified, encompassing a wide range of cardiac, respiratory, gastrointestinal, renal, neurological, ophthalmological, and dermatological pathologies. Individuals with high microfilarial densities and residing in an endemic country were at greater risk of suffering from atypical manifestations. Conclusions: Our findings have important implications for understanding the clinical spectrum of conditions associated with Loa loa infection, which extends well beyond the classical eyeworm and Calabar swellings. As case reports may overestimate the true rate of atypical manifestations in endemic populations, large-scale, longitudinal clinico-epidemiological studies will be required to refine our estimates and demonstrate causality between loiasis and the breadth of clinical manifestations reported. Even if the rates of atypical presentations were found to be lower, given that residents of loiasis-endemic areas are both numerous and the group most at risk of severe atypical manifestations, our conclusions support the recognition of loiasis as a significant public health burden across Central Africa.

Journal article

Turner HC, Walker M, Pion SDS, McFarland DA, Bundy DAP, Basanez M-Get al., 2019, Economic evaluations of onchocerciasis interventions: a systematic review and research needs, Tropical Medicine and International Health, Vol: 24, Pages: 788-816, ISSN: 1360-2276

ObjectiveTo provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps.MethodA systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. No date or language stipulations were applied to the searches.ResultsWe identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost‐effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis‐associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost‐effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability‐adjusted life year (DALY) averted of annual MDA varies between US$3 and US$30 (cost year variable).ConclusionsThe cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond.

Journal article

Dixon MA, Braae UC, Winskill P, Walker M, Devleesschauwer B, Gabriël S, Basáñez M-Get al., 2019, Strategies for tackling Taenia solium taeniosis/cysticercosis: A systematic review and comparison of transmission models, including an assessment of the wider Taeniidae family transmission models, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727

BackgroundThe cestode Taenia solium causes the neglected (zoonotic) tropical disease cysticercosis, a leading cause of preventable epilepsy in endemic low and middle-income countries. Transmission models can inform current scaling-up of control efforts by helping to identify, validate and optimise control and elimination strategies as proposed by the World Health Organization (WHO).Methodology/Principal findingsA systematic literature search was conducted using the PRISMA approach to identify and compare existing T. solium transmission models, and related Taeniidae infection transmission models. In total, 28 modelling papers were identified, of which four modelled T. solium exclusively. Different modelling approaches for T. solium included deterministic, Reed-Frost, individual-based, decision-tree, and conceptual frameworks. Simulated interventions across models agreed on the importance of coverage for impactful effectiveness to be achieved.Other Taeniidae infection transmission models comprised force-of-infection (FoI), population-based (mainly Echinococcus granulosus) and individual-based (mainly E. multilocularis) modelling approaches. Spatial structure has also been incorporated (E. multilocularis and Taenia ovis) in recognition of spatial aggregation of parasite eggs in the environment and movement of wild animal host populations.Conclusions/SignificanceGaps identified from examining the wider Taeniidae family models highlighted the potential role of FoI modelling to inform model parameterisation, as well as the need for spatial modelling and suitable structuring of interventions as key areas for future T. solium model development. We conclude that working with field partners to address data gaps and conducting cross-model validation with baseline and longitudinal data will be critical to building consensus-led and epidemiological setting-appropriate intervention strategies to help fulfil the WHO targets.

Journal article

Whittaker C, Kamgno J, Klion A, Walker M, Pion SDS, Chesnais CB, Lambert B, Kuesel A, Basanez M-G, Boussinesq Met al., 2019, THE EFFECT OF ALBENDAZOLE TREATMENT ON LOA LOA: A SYSTEMATIC REVIEW, META-ANALYSIS AND MODELLING STUDY, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 559-560, ISSN: 0002-9637

Conference paper

Dunn JC, Walker M, Bettis AA, Wright JE, Wyine NY, Lwin AMM, Maung NS, Anderson RMet al., 2019, PREDISPOSITION AND HOUSEHOLD CLUSTERING OF SOIL-TRANSMITTED HELMINTH INFECTION EVIDENT IN MYANMAR COMMUNITIES THAT HAVE RECEIVED EXTENSIVE MASS DRUG ADMINISTRATION, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 616-617, ISSN: 0002-9637

Conference paper

Verver S, Walker M, Kim YE, Fobi G, Tekle AH, Zouré HGM, Wanji S, Boakye DA, Kuesel AC, de Vlas SJ, Boussinesq M, Basanez MG, Stolk WAet al., 2018, How can onchocerciasis elimination in Africa be accelerated? Modelling the impact of increased ivermectin treatment frequency and complementary vector control, Clinical Infectious Diseases, Vol: 66, Pages: S267-S274, ISSN: 1058-4838

Background:Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated.Methods:We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination.Results:Areas with 40%–50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%–80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control.Conclusions:Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

Journal article

Routledge I, Walker M, Cheke R, Bhatt S, Baleguel Nkot P, Matthews G, Baleguel D, Dobson H, Wiles TL, Basanez MGet al., 2018, Modelling the impact of larviciding on the population dynamics and biting rates of Simulium damnosum s.l.: implications for vector control as a complementary strategy for onchocerciasis elimination in Africa, Parasites & Vectors, Vol: 11, Pages: 1-16, ISSN: 1756-3305

Background:In 2012, the World Health Organization set goals for the elimination of onchocerciasis transmission by 2020 in selected African countries. Epidemiological data and mathematical modelling have indicated that elimination may not be achieved with annual ivermectin distribution in all endemic foci. Complementary and alternative treatment strategies (ATS), including vector control, will be necessary. Implementation of vector control will require that the ecology and population dynamics of Simuliumdamnosum sensu latobe carefully considered.Methods:We adapted our previous SIMuliid POPulation dynamics (SIMPOP) model to explore the impact of larvicidal insecticides on S.damnosums.l.biting rates in different ecological contexts and to identify how frequently and for how long vector control should be continued to sustain substantive reductions in vector biting. SIMPOP was fitted to data from large-scale aerial larviciding trials in savannah sites (Ghana) and small-scale ground larviciding trials in forest areas (Cameroon). The model was validated against independent data from Burkina Faso/Côte d’Ivoire (savannah) and Bioko (forest). Scenario analysis explored the effects of ecological and programmatic factors such as pre-control daily biting rate (DBR) and larviciding scheme design on reductions and resurgences in biting rates.Results: The estimated efficacy of large-scale aerial larviciding in the savannah was greater than that of ground-based larviciding in the forest. Small changes in larvicidal efficacy can have large impacts on intervention success. At 93% larvicidal efficacy (a realistic value based on field trials), 10 consecutive weekly larvicidal treatments would reduce DBRs by 96% (e.g. from 400 to 16bites/person/day). At 70% efficacy, and for 10 weekly applications, the DBRwould decrease by 67% (e.g. from 400 to 132bites/person/day). Larviciding is more likely to succeed in areas with lower water temperatures and where blackfly species have lo

Journal article

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