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Niamsi-Emalio Y, Nana-Djeunga HC, Chesnais CB, et al., 2021, Unusual localization of blood-borne loa loa microfilariae in the skin depends on microfilarial density in the blood: Implications for onchocerciasis diagnosis in coendemic areas., Clinical Infectious Diseases, Vol: 72, Pages: S158-S164, ISSN: 1058-4838
BACKGROUND: The diagnostic gold standard for onchocerciasis relies on identification and enumeration of (skin-dwelling) Onchocerca volvulus microfilariae (mf) using the skin snip technique (SST). In a recent study, blood-borne Loa loa mf were found by SST in individuals heavily infected with L. loa, and microscopically misidentified as O. volvulus due to their superficially similar morphology. This study investigates the relationship between L. loa microfilarial density (Loa MFD) and the probability of testing SST positive. METHODS: A total of 1053 participants from the (onchocerciasis and loiasis coendemic) East Region in Cameroon were tested for (1) Loa MFD in blood samples, (2) O. volvulus presence by SST, and (3) Immunoglobulin (Ig) G4 antibody positivity to Ov16 by rapid diagnostic test (RDT). A Classification and Regression Tree (CART) model was used to perform a supervised classification of SST status and identify a Loa MFD threshold above which it is highly likely to find L. loa mf in skin snips. RESULTS: Of 1011 Ov16-negative individuals, 28 (2.8%) tested SST positive and 150 (14.8%) were L. loa positive. The range of Loa MFD was 0-85 200 mf/mL. The CART model subdivided the sample into 2 Loa MFD classes with a discrimination threshold of 4080 (95% CI, 2180-12 240) mf/mL. The probability of being SST positive exceeded 27% when Loa MFD was >4080 mf/mL. CONCLUSIONS: The probability of finding L. loa mf by SST increases significantly with Loa MFD. Skin-snip polymerase chain reaction would be useful when monitoring onchocerciasis prevalence by SST in onchocerciasis-loiasis coendemic areas.
Dolo H, Coulibaly YI, Sow M, et 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.
Toor J, Adams ER, Aliee M, et 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.
Dixon M, Winskill P, Harrison W, et al., 2021, Taenia solium taeniasis / cysticercosis: from parasite biology and immunology to diagnosis and control, Advances in Parasitology, Vol: 112, Pages: 133-217, ISSN: 0065-308X
Infection with the pork tapeworm (Taenia solium) is responsible for a substantial global burden of disease, not only restricted to its impact on human health, but also resulting in a considerable economic burden to smallholder pig farmers due to pig cysticercosis infection. The life-cycle, parasitology and immunology of T. solium are complex, involving pigs(the intermediate host, harbouring the larval metacestode stage), humans(the definitive host, harbouring the adult tapeworm, in addition to acting as accidental intermediate hosts) and the environment (the source of infection with eggs/proglottids). We review the parasitology, immunology, and epidemiology of the infection associated with each of the T. solium life-cycle stages, including the pre-adult/adult tapeworm responsible for human taeniasis; post-oncosphere and cysticercus associated with porcine and human cysticercosis, and the biological characteristics of eggs in the environment. We discuss the burden associated, in endemic settings, with neurocysticercosis (NCC) in humans, and the broader cross-sectoral economic impact associated both with NCC and porcine cysticercosis, the latter impacting food-value chains. Existing tools for diagnostics and control interventions that target different stages of the T. solium transmission cycle are reviewed and their limitations discussed. Currently, no national T. solium control programmes have been established in endemic areas, with further work required to identify optimal strategies according to epidemiological setting. There is increasing evidence suggesting that cross-sectoral interventions which target the parasite in both the human and pig host provide the most effective approaches for achieving control and ultimately elimination. We discuss future avenues for research on T. soliumto support the attainement of the goals proposed in the revised World Heal
Hamley JID, Blok DJ, Walker M, et 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.
Cheke RA, Little KE, Young S, et 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, ADVANCES IN PARASITOLOGY, VOL 112, Editors: Rollinson, Stothard, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 1-50
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Clark J, Stolk WA, Basáñez M-G, et al., 2021, How modelling can help steer the course set by the World Health Organization 2021-2030 roadmap on neglected tropical diseases., Gates Open Res, Vol: 5
The World Health Organization recently launched its 2021-2030 roadmap, Ending the Neglect to Attain the Sustainable Development Goals , an updated call to arms to end the suffering caused by neglected tropical diseases. Modelling and quantitative analyses played a significant role in forming these latest goals. In this collection, we discuss the insights, the resulting recommendations and identified challenges of public health modelling for 13 of the target diseases: Chagas disease, dengue, gambiense human African trypanosomiasis (gHAT), lymphatic filariasis (LF), onchocerciasis, rabies, scabies, schistosomiasis, soil-transmitted helminthiases (STH), Taenia solium taeniasis/ cysticercosis, trachoma, visceral leishmaniasis (VL) and yaws. This piece reflects the three cross-cutting themes identified across the collection, regarding the contribution that modelling can make to timelines, programme design, drug development and clinical trials.
Dolo H, Coulibaly YI, Sow M, et 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
Dixon MA, Winskill P, Harrison W, et 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.
Basanez M-G, Milton P, Hamley J, et 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.
Hamley J, Walker M, Coffeng LE, et 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.
Walker M, Hamley JID, Milton P, et 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.
Behrend M, Basanez M-G, Hamley JID, et al., 2020, Modelling for policy: the five principles of the Neglected Tropical Diseases Modelling Consortium, PLoS Neglected Tropical Diseases, ISSN: 1935-2727
Nana Djeunga H, Domche A, Niamsi-Emalio Y, et 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
Dixon M, Braae UC, Winskill P, et 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.
Kim JYH, Ledien J, Rodriguez-Monguí E, et al., 2019, Global Trends of Seroprevalence and Universal Screening Policy for Chagas Disease in Donors: a systematic review and meta-analysis, medRxiv
<h4>Background</h4> Screening for Trypanosoma cruzi among blood and organ donors is essential to reduce Chagas disease transmission. The World Health Organization (WHO) has prioritised curtailing transmission in blood banks (BBs) and transplantation centres (TCs) by 50% by 2025 and 100% by 2030. This study aims to update the situation on T. cruzi screening strategies in BBs and TCs to evaluate the evolution of seroprevalence and the achievement of screening milestones globally. <h4>Methods</h4> We used published articles and government reports on seroprevalence data and screening policies in BBs and TCs across the world. We conducted meta-analyses of T. cruzi seroprevalence estimates by who region, endemicity status, and country, and used meta-regression to identify the covariates influencing the estimates. Publication bias and sensitivity analyses were also conducted. <h4>Results</h4> Based on 99 studies and reports and found a global pattern of increased universal screening policies (USPs) in BBs from 1990 to 2018. We found information for 50 countries, of which 44 (88%) have implemented USPs and 21 (42%) achieved 100% coverage by 2015. Out of the 21 Chagas-disease endemic countries, 20 are in advanced USPS stages, and 18 achieved 100% coverage by 2015. Latin America (LA) was the first region to start USPS since the 1990s and 19 countries are in advanced stages of implementation and by 2015 there is evidence of 100% coverage in 15 LA countries. In the Caribbean Region, USPs are still in early implementation stages and by 2015 only five out of 24 countries have achieved 100% coverage. Outside Latin America and the Caribbean, there are USPs only in the USA, which initiated in 2007 and with 100% coverage in 2016. In Europe, there are no USPs, but some countries have implemented selective screening of at-risk donors in the UK, Spain, France and Switzerland. Whereas Sweden and Italy have implemented a deferral system. For TCs, nation
Deol AK, Fleming FM, Calvo-Urbano B, et 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
Hamley JID, Milton P, Walker M, et 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
Buell KG, Whittaker C, Chesnais CB, et 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.
Fodjo SJN, Menon S, Hotterbeekx A, et al., 2019, ONCHOCERCIASIS-ASSOCIATED EPILEPSY: THE EPIDEMIOLOGICAL EVIDENCE, Publisher: OXFORD UNIV PRESS, Pages: S56-S56, ISSN: 0035-9203
Fodjo SJN, Menon S, Hotterbeekx A, et al., 2019, ONCHOCERCIASIS-ASSOCIATED EPILEPSY: THE EPIDEMIOLOGICAL EVIDENCE, Publisher: OXFORD UNIV PRESS, Pages: S58-S59, ISSN: 0035-9203
Colebunders R, Siewe Fodjo JN, Hopkins A, et al., 2019, From river blindness to river epilepsy: Implications for onchocerciasis elimination programmes, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727
Current onchocerciasis elimination programmes do not include identification and management of onchocerciasis-associated epilepsy (OAE) in their strategies. Creating awareness about OAE will increase community-directed treatment with ivermectin (CDTI) adherence, particularly in areas of high prevalence, while motivating funders and stakeholders not to relent their efforts in the fight against onchocerciasis. Strengthening onchocerciasis elimination efforts should be prioritised wherever epilepsy prevalence is high in order to reduce OAE-related morbidity and mortality. In such areas, alternative treatment strategies including biannual CDTI, ground larviciding of blackfly breeding sites, and/or treatment with moxidectin should be considered. Addressing the OAE disease burden in these generally remote onchocerciasis-endemic regions confronted with poverty, weak healthcare infrastructures, and insecurity goes beyond current onchocerciasis elimination plans. New strategies with appropriate budgets are required. A morbidity management and disease prevention (MMDP) strategy, fully integrated into the health system, must be developed by multidisciplinary working groups involving neglected tropical disease (NTD) and epilepsy specialists, advocacy experts, and persons from affected communities. ‘River epilepsy’ needs to be urgently recognised and placed in the international development and NTD agendas.
Turner HC, Walker M, Pion SDS, et 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.
Grillet ME, Hernandez-Villena JV, Llewellyn MS, et al., 2019, Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region, Lancet Infectious Diseases, Vol: 19, Pages: E149-E161, ISSN: 1473-3099
In the past 5–10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.
Dixon MA, Braae UC, Winskill P, et 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.
Whittaker C, Kamgno J, Klion A, et al., 2019, THE EFFECT OF ALBENDAZOLE TREATMENT ON <i>LOA LOA</i>: 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
Cucunuba Perez Z, Nouvellet P, Peterson J, et al., 2018, Complementary paths to chagas disease elimination: the impact of combining vector control with aetiological treatment, Clinical Infectious Diseases, Vol: 66, Pages: S293-S300, ISSN: 1058-4838
Background:The World Health Organization’s 2020 goals for Chagas disease are (1) interrupting vector-borne intradomiciliary transmission and (2) having all infected people under care in endemic countries. Insecticide spraying has proved efficacious for reaching the first goal, but active transmission remains in several regions. For the second, treatment has mostly been restricted to recently infected patients, who comprise only a small proportion of all infected individuals.Methods:We extended our previous dynamic transmission model to simulate a domestic Chagas disease transmission cycle and examined the effects of both vector control and etiological treatment on achieving the operational criterion proposed by the Pan American Health Organization for intradomiciliary, vectorial transmission interruption (ie, <2% seroprevalence in children <5 years of age).Results:Depending on endemicity, an antivectorial intervention that decreases vector density by 90% annually would achieve the transmission interruption criterion in 2–3 years (low endemicity) to >30 years (high endemicity). When this strategy is combined with annual etiological treatment in 10% of the infected human population, the seroprevalence criterion would be achieved, respectively, in 1 and 11 years.Conclusions:Combining highly effective vector control with etiological (trypanocidal) treatment in humans would substantially reduce time to transmission interruption as well as infection incidence and prevalence. However, the success of vector control may depend on prevailing vector species. It will be crucial to improve the coverage of screening programs, the performance of diagnostic tests, the proportion of people treated, and the efficacy of trypanocidal drugs. While screening and access can be incremented as part of strengthening the health systems response, improving diagnostics performance and drug efficacy will require further research.
Verver S, Walker M, Kim YE, et 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.
Routledge I, Walker M, Cheke R, et 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
Zain SNM, Basanez M-G, 2018, Collaborate or collapse: capacity building in zoonotic and neglected tropical disease modelling, Trends in Parasitology, Vol: 34, Pages: 356-358, ISSN: 0169-4758
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