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Infection by Taenia solium poses a major burden across endemic countries. The World Health Organization (WHO) 2021–2030 Neglected Tropical Diseases roadmap has proposed that 30% of endemic countries achieve intensified T. solium control in hyperendemic areas by 2030. Understanding geographical variation in age-prevalence profiles and force-of-infection (FoI) estimates will inform intervention designs across settings.Human taeniasis (HTT) and human cysticercosis (HCC) age-prevalence data from 16 studies in Latin America, Africa and Asia were extracted through a systematic review. Catalytic models, incorporating diagnostic performance uncertainty, were fitted to the data using Bayesian methods, to estimate rates of antibody (Ab)-seroconversion, infection acquisition and Ab-seroreversion or infection loss. HCC FoI and Ab-seroreversion rates were also estimated across 23 departments in Colombia from 28,100 individuals.Across settings, there was extensive variation in all-ages seroprevalence. Evidence for Ab- seroreversion or infection loss was found in most settings for both HTT and HCC and for HCC Ab- seroreversion in Colombia. The average duration until humans became Ab-seropositive/infected decreased as all-age (sero)prevalence increased. There was no clear relationship between the average duration humans remain Ab-seropositive and all-age seroprevalence.Marked geographical heterogeneity in T. solium transmission rates indicate the need for setting- specific intervention strategies to achieve the WHO goals.

Fil: Sykes, Abagael. London Centre for Neglected Tropical Disease Research, Londres, Inglaterra Fil: Larrieu, Edmundo. Universidad Nacional de Rio Negro, Escuela de Veterinaria. Rio Negro, Argentina. Fil: Poggio, Veronica. Instituto Cesar Milstein, Buenos Aires Fil: Cespedes, Graciela. Instituto Malbran, Parasitologia, Buenos Aires Fil: Mugica, Guillermo. Ministerio de salud de rio negro, Salud Ambiental, Rio Negro Fil: Basanez, Maria Gloria. London Centre for Neglected Tropical Disease Research, Londres, Inglaterra Fil: Prada, Joaquin. London Centre for Neglected Tropical Disease Research, Londres, Inglaterra Echinococcus granulosus sensu lato is a globally prevalent zoonotic parasitic cestode leading to cystic echinococcosis (CE) in both humans and sheep with both medical and financial impacts, whose reduction requires the application of a One Health approach to its control. Regarding the animal health component of this approach, lack of accurate and practical diagnostics in livestock impedes the assessment of disease burden and the implementation and evaluation of control strategies. We use of a Bayesian Latent Class Analysis (LCA) model to estimate ovine CE prevalence in sheep samples from the Río Negro province of Argentina accounting for uncertainty in the diagnostics. We use model outputs to evaluate the performance of a novel recombinant B8/2 antigen B subunit (rEgAgB8/2) indirect enzyme-linked immunosorbent assay (ELISA) for detecting E. granulosus in sheep. Necropsy (as a partial gold standard), western blot (WB) and ELISA diagnostic data were collected from 79 sheep within two Río Negro slaughterhouses, and used to estimate individual infection status (assigned as a latent variable within the model). Using the model outputs, the performance of the novel ELISA at both individual and flock levels was evaluated, respectively, using a receiver operating characteristic (ROC) curve, and simulating a range of sample sizes and prevalence levels within hypothetical flocks. The estimated (mean) prevalence of ovine CE was 27.5% (95%Bayesian credible interval (95%BCI): 13.8%–58.9%) within the sample population. At the individual level, the ELISA had a mean sensitivity and specificity of 55% (95%BCI: 46%–68%) and 68% (95%BCI: 63%–92%), respectively, at an optimal optical density (OD) threshold of 0.378. At the flock level, the ELISA had an 80% probability of correctly classifying infection at an optimal cut-off threshold of 0.496. These results suggest that the novel ELISA could play a useful role as a flock-level diagnostic for CE surveillance in the region, supplementing surveillance activities in the human population and thus strengthening a One Health approach. Importantly, selection of ELISA cut-off threshold values must be tailored according to the epidemiological situation Echinococcus granulosus sensu lato es un cestodo parasitario zoonótico de prevalencia mundial que causa equinococosis quística (EC) tanto en humanos como en ovejas con impactos médicos y financieros, cuya reducción requiere la aplicación de un enfoque de One Health para su control. Con respecto al componente de salud animal de este enfoque, la falta de diagnósticos precisos y prácticos en el ganado impide la evaluación de la carga de la enfermedad y la implementación y evaluación de estrategias de control. Usamos un modelo Bayesiano de Análisis de Clase Latente (LCA) para estimar la prevalencia de CE ovina en muestras de ovinos de la provincia de Río Negro de Argentina teniendo en cuenta la incertidumbre en el diagnóstico. Utilizamos los resultados del modelo para evaluar el rendimiento de un nuevo B8/2 recombinante subunidad del antígeno B (rEgAgB8/2) ensayo inmunoabsorbente ligado a enzimas indirecto (ELISA) para detectar E. granulosus en ovejas Los datos de diagnóstico de necropsia (como estándar de oro parcial), western blot (WB) y ELISA se recopilaron de 79 ovejas dentro de dos mataderos de Río Negro, y se utilizó para estimar el estado de infección individual (asignado como variable latente dentro del modelo). Utilizando los resultados del modelo, se evaluó el rendimiento del nuevo ELISA a nivel individual y de parvada, respectivamente, utilizando una curva característica operativa del receptor (ROC), y simular un rango de tamaños de muestra y niveles de prevalencia dentro de bandadas hipotéticas. La (media) estimada la prevalencia de EC ovina fue del 27,5 % (95 % intervalo creíble bayesiano (95 % BCI): 13,8 %–58,9 %) dentro de la muestra población. A nivel individual, el ELISA tuvo una sensibilidad y especificidad medias del 55% (95%BCI: 46%–68%) y 68 % (95 % BCI: 63 %–92 %), respectivamente, en un umbral óptimo de densidad óptica (OD) de 0,378. en el rebaño nivel, el ELISA tenía un 80% de probabilidad de clasificar correctamente la infección en un umbral de corte óptimo de 0,496. Estos resultados sugieren que el nuevo ELISA podría desempeñar un papel útil como diagnóstico a nivel de parvada para la vigilancia de CE en la región, complementando las actividades de vigilancia en la población humana y fortaleciendo así una Enfoque de salud. Es importante destacar que la selección de los valores de umbral de corte de ELISA debe adaptarse de acuerdo con la situación epidemiológica

BackgroundAlbendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown the drug to be characterised by significant inter-individual pharmacokinetic variation. This variation is thought to have important consequences for treatment success, but current understanding of the factors associated with this variation remains incomplete.Methodology/Principal FindingsWe carried out a systematic review to identify references containing temporally disaggregated data on the blood concentration of albendazole and/or (its pharmacologically-active metabolite) albendazole sulfoxide following a single oral dose. These data were then integrated into a mathematical modelling framework to infer key pharmacokinetic parameters and relate them to characteristics of the populations being treated. These characteristics included age, weight, sex, dosage, infection status, and whether patients had received a fatty meal prior to treatment or other drugs alongside albendazole. Our results highlight a number of factors systematically associated with albendazole pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. These factors impact different aspects of the drug’s pharmacokinetic profile. Whilst age is significantly associated with albendazole sulfoxide half-life, receipt of a fatty meal prior to treatment was associated with increased albendazole bioavailability (and by extension, peak blood concentration and total drug exposure following the dose). Parasitic infection (particularly echinococcosis and neurocysticercosis) was associated with altered pharmacokinetic parameters, with infected populations displaying distinct characteristics to uninfected ones.Conclusions/SignificanceThese results highlight the extensive inter-individual variation that characterises albendazole pharmacokinetics and provides insight into some of the factors associated with this variation.Author SummaryAlbendazole is a broad-spectrum anti-parasitic medication widely used in the treatment of a variety of parasitic worm infections. Previous studies have demonstrated significant variation in the pharmacokinetics of albendazole (and its pharmacologically active metabolite albendazole sulfoxide), leading to substantial inter-individual variability in blood plasma concentrations following a dose of the drug being given. This variation is thought to have important consequences for treatment success but our understanding of the factors driving this variation remain incomplete. In this study, we carried out a systematic review to identify references with data on albendazole and albendazole sulfoxide concentrations in the blood following a single oral dose. We then fitted a mathematical model of albendazole pharmacokinetics to these data to infer key pharmacokinetic parameters and relate them to characteristics of the populations being treated. We found that receipt of a fatty meal prior to treatment was associated with increased albendazole bioavailability, that the half-life of albendazole sulfoxide in the blood varied significantly with age, and that both echinococcosis and neurocysticercosis were associated with altered pharmacokinetic profiles compared to healthy individuals. Our work provides insight into some of the factors systematically associated with variation in albendazole pharmacokinetics.

The accuracy of screening tests for detecting cystic echinococcosis (CE) in livestock depends on characteristics of the host–parasite interaction and the extent of serological cross-reactivity with other taeniid species. The AgB8 kDa protein is considered to be the most specific native or recombinant antigen for immunodiagnosis of ovine CE. A particular DNA fragment coding for rAgB8/2 was identified, that provides evidence of specific reaction in the serodiagnosis of metacestode infection. We developed and validated an IgG Enzyme Linked Immunosorbent Assay (ELISA) test using a recombinant antigen B sub-unit EgAgB8/2 (rAgB8/2) of Echinoccocus granulosus sensu lato (s.l.) to estimate CE prevalence in sheep. A 273bp DNA fragment coding for rAgB8/2 was expressed as a fusion protein (∼30 kDa) and purified by affinity chromatography. Evaluation of the analytical and diagnostic performance of the ELISA followed the World Organisation for Animal Health (OIE) manual, including implementation of serum panels from: uninfected lambs (n=79); experimentally infected (with 2,000 E. granulosus s.l. eggs each) sheep with subsequent evidence of E. granulosus cysts by necropsy (n=36), and animals carrying other metacestode/trematode infections (n=20). The latter were used to assess the cross-reactivity of rAgB8/2, with these animals being naturally infected with Taenia hydatigena, Thysanosoma actinioides and/or Fasciola hepatica. EgAgB8/2 showed cross-reaction with only one serum sample from a sheep infected with Ta. hydatigena out of the 20 animals tested. Furthermore, the kinetics of the humoral response over time in five 6-month old sheep, each experimentally infected with 2,000 E. granulosus s.l. eggs, was evaluated up to 49 weeks (approximately one year) post infection (n=5). The earliest detectable IgG response against rAgB8/2 was observed in sera from two and four sheep, 7 and 14 days after experimental infection, respectively. The highest immune response across all five animals was found 16 to 24 weeks post infection.

The accuracy of screening tests for detecting cystic echinococcosis (CE) in livestock depends on characteristics of the host-parasite interaction and the extent of serological cross-reactivity with other taeniid species. The AgB8 kDa protein is considered to be the most specific native or recombinant antigen for immunodiagnosis of ovine CE. A particular DNA fragment coding for rAgB8/2 was identified, that provides evidence of specific reaction in the serodiagnosis of metacestode infection. We developed and validated an IgG Enzyme Linked Immunosorbent Assay (ELISA) test using a recombinant antigen B sub-unit EgAgB8/2 (rAgB8/2) of

Efforts are being directed toward the elimination of onchocerciasis transmission in endemic areas with community-directed treatment with ivermectin (CDTI) in Africa, which greatly reduces onchocerciasis-associated disease. However, onchocerciasis remains a major public health problem in areas of South Sudan, the Democratic Republic of the Congo, Cameroon, and the Central African Republic. Strengthening onchocerciasis elimination efforts in areas with a high prevalence of disease burden is crucial to decrease transmission, morbidity, and mortality. We argue that clinical trials are needed to investigate the safety and efficacy of ivermectin treatment of Onchocerca volvulus-infected pregnant women and children younger than 5 years. Crucially, 6-monthly administration of ivermectin in school-age children at risk of onchocerciasis-associated epilepsy could be achieved by supplementing annual CDTI with an extra round of ivermectin treatment during Child Health Days in schools and/or other distribution sites every year. These strategies would help achieve the elimination of onchocerciasis and its associated disease burden. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Background In line with movement restrictions and physical distancing essential for the control of the COVID-19 pandemic, WHO recommended postponement of all neglected tropical disease (NTD) control activities that involve community-based surveys, active case finding, and mass drug administration in April, 2020. Following revised guidance later in 2020, and after interruptions to NTD programmes of varying lengths, NTD programmes gradually restarted in the context of an ongoing pandemic. However, ongoing challenges and service gaps have been reported. This study aimed to evaluate the potential effect of the programmatic interruptions and strategies to mitigate this effect. Methods For seven NTDs, namely soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis, trachoma, visceral leishmaniasis, and human African trypanosomiasis, we used mathematical transmission models to simulate the effect of programme interruptions on the dynamics of each of these diseases in different endemic settings. We also explored the potential benefit of implementing mitigation strategies, primarily in terms of minimising the delays to control targets. Findings We show that the effect of the COVID-19-induced interruption in terms of delay to achieving elimination goals might in some cases be much longer than the duration of the interruption. For schistosomiasis, onchocerciasis, trachoma, and visceral leishmaniasis, a mean delay of 2–3 years for a 1-year interruption is predicted in areas of highest prevalence. We also show that these delays can largely be mitigated by measures such as additional mass drug administration or enhanced case-finding. Interpretation The COVID-19 pandemic has brought infectious disease control to the forefront of global consciousness. It is essential that the NTDs, so long neglected in terms of research and financial support, are not overlooked, and remain a priority in health service planning and funding. Funding Bill & Melinda Gates Foundation, Medical Research Council, and the UK Foreign, Commonwealth & Development Office.

The Infectious Diseases Data Observatory (IDDO, https://www.iddo.org) has launched a clinical data platform for the collation, curation, standardisation and reuse of individual participant data (IPD) on treatments for two of the most globally important neglected tropical diseases (NTDs), schistosomiasis (SCH) and soil-transmitted helminthiases (STHs). This initiative aims to harness the power of data-sharing by facilitating collaborative joint analyses of pooled datasets to generate robust evidence on the efficacy and safety of anthelminthic treatment regimens. A crucial component of this endeavour has been the development of a Research Agenda to promote engagement with the SCH and STH research and disease control communities by highlighting key questions that could be tackled using data shared through the IDDO platform. Here, we give a contextual overview of the priority research themes articulated in the Research Agenda—a ‘living’ document hosted on the IDDO website—and describe the three-stage consultation process behind its development. We also discuss the sustainability and future directions of the platform, emphasising throughout the power and promise of ethical and equitable sharing and reuse of clinical data to support the elimination of NTDs.

Background In onchocerciasis endemic areas in Africa, heterogenous biting rates by blackfly vectors on humans are assumed to partially explain age- and sex-dependent infection patterns with Onchocerca volvulus. To underpin these assumptions and further improve predictions made by onchocerciasis transmission models, demographic patterns in antibody responses to salivary antigens of Simulium damnosum s.l. are evaluated as a measure of blackfly exposure. Methodology/Principal findings Recently developed IgG and IgM anti-saliva immunoassays for S. damnosum s.l. were applied to blood samples collected from residents in four onchocerciasis endemic villages in Ghana. Demographic patterns in antibody levels according to village, sex and age were explored by fitting generalized linear models. Antibody levels varied between villages but showed consistent patterns with age and sex. Both IgG and IgM responses declined with increasing age. IgG responses were generally lower in males than in females and exhibited a steeper decline in adult males than in adult females. No sex-specific difference was observed in IgM responses. Conclusions/Significance The decline in age-specific antibody patterns suggested development of immunotolerance or desensitization to blackfly saliva antigen in response to persistent exposure. The variation between sexes, and between adults and youngsters may reflect differences in behaviour influencing cumulative exposure. These measures of antibody acquisition and decay could be incorporated into onchocerciasis transmission models towards informing onchocerciasis control, elimination, and surveillance., Author summary Onchocerciasis, a disease caused by the helminth parasite Onchocerca volvulus, is transmitted by the bites of female Simulium blackflies. The disease is still endemic in many African countries, and the World Health Organization has proposed elimination of its transmission in 12 countries by 2030. Understanding the heterogeneity in human exposure to vector bites can help discern which portion of the population is at higher risk of acquiring/ transmitting infection and is fundamental to identifying target groups for serological monitoring and transmission control. Traditionally, blackfly biting rates are estimated by performing human landing catches, a method that is often considered unethical and which can be unreliable as a representative measure. Therefore, we used our recently developed immunoassays to measure human antibody responses to antigens contained in the saliva of blackflies and deposited into human skin when they bloodfeed. In onchocerciasis endemic communities in Ghana, we measured antibody responses to understand age- and/or sex-related demographic patterns in vector exposure. We observed lower antibody responses in males compared to in females, and a substantial decline with increasing age, suggesting that high blackfly biting pressure induces desensitization in the human host.

Background: Childhood anaemia affects 1.8 billion people globally. Little is known about the long-term impact of mass drug administration (MDA) for the control of soil-transmitted helminthiases (STH) on the spatiotemporal variation of anaemia prevalence and severity. We describe the long-term spatiotemporal impact of a 5-year STH MDA programme (2007–2011) on the prevalence of anaemia and anaemia severity in school-aged children (SAC) in Burundi. Methodology/Principal Findings: We used annual haemoglobin concentration and STH data collected during 2007–2011 in 31 schools in Burundi. Spatial dependence in prevalence and severity of anaemia was assessed using semivariograms. Bayesian geostatistical models were developed to (a) quantify the role of STH (adjusted for other anaemia determinants) in the spatiotemporal distribution of anaemia prevalence/severity, and (b) predict the geographical variation of both outcomes across Burundi. Adjusted population data were used to estimate the geographical distribution of the number of SAC at risk of anaemia and with low and moderate/severe anaemia. Infections with Ascaris lumbricoides and Trichuris trichiura were positively and significantly associated with childhood anaemia; hookworm infections were not. A significant decrease in anaemia prevalence, from 40–50% (2008) to 10–20% (2011) was predicted in western areas. The predicted prevalence of low-severity anaemia decreased from 40–50% (2008) to

Echinococcus granulosus sensu lato is a globally prevalent zoonotic parasitic cestode leading to cystic echinococcosis (CE) in both humans and sheep with both medical and financial impacts, whose reduction requires the application of a One Health approach to its control. Regarding the animal health component of this approach, lack of accurate and practical diagnostics in livestock impedes the assessment of disease burden and the implementation and evaluation of control strategies. We use of a Bayesian Latent Class Analysis (LCA) model to estimate ovine CE prevalence in sheep samples from the Río Negro province of Argentina accounting for uncertainty in the diagnostics. We use model outputs to evaluate the performance of a novel recombinant B8/2 antigen B subunit (rEgAgB8/2) indirect enzyme-linked immunosorbent assay (ELISA) for detecting E. granulosus in sheep. Necropsy (as a partial gold standard), western blot (WB) and ELISA diagnostic data were collected from 79 sheep within two Río Negro slaughterhouses, and used to estimate individual infection status (assigned as a latent variable within the model). Using the model outputs, the performance of the novel ELISA at both individual and flock levels was evaluated, respectively, using a receiver operating characteristic (ROC) curve, and simulating a range of sample sizes and prevalence levels within hypothetical flocks. The estimated (mean) prevalence of ovine CE was 27.5% (95%Bayesian credible interval (95%BCI): 13.8%–58.9%) within the sample population. At the individual level, the ELISA had a mean sensitivity and specificity of 55% (95%BCI: 46%–68%) and 68% (95%BCI: 63%–92%), respectively, at an optimal optical density (OD) threshold of 0.378. At the flock level, the ELISA had an 80% probability of correctly classifying infection at an optimal cut-off threshold of 0.496. These results suggest that the novel ELISA could play a useful role as a flock-level diagnostic for CE surveillance in the region, supplementing surveillance activities in the human population and thus strengthening a One Health approach. Importantly, selection of ELISA cut-off threshold values must be tailored according to the epidemiological situation., Highlights • Development of a Bayesian LCA model for ovine cystic echinococcosis (CE) in Argentina. • Evaluation of diagnostic performance for a novel rEgAgB8/2 indirect ELISA. • Identification of optimal ELISA thresholds for use as a flock-level surveillance tool. • Improvement of CE surveillance in sheep will help strengthen the One Health approach.

Background Simulium damnosum sensu lato (s.l.) blackflies transmit Onchocerca volvulus, a filarial nematode that causes human onchocerciasis. Human landing catches (HLCs) is currently the sole method used to estimate blackfly biting rates but is labour-intensive and questionable on ethical grounds. A potential alternative is to measure host antibodies to vector saliva deposited during bloodfeeding. In this study, immunoassays to quantify human antibody responses to S. damnosum s.l. saliva were developed, and the salivary proteome of S. damnosum s.l. was investigated. Methodology/Principal findings Blood samples from people living in onchocerciasis-endemic areas in Ghana were collected during the wet season; samples from people living in Accra, a blackfly-free area, were considered negative controls and compared to samples from blackfly-free locations in Sudan. Blackflies were collected by HLCs and dissected to extract their salivary glands. An ELISA measuring anti-S. damnosum s.l. salivary IgG and IgM was optimized and used to quantify the humoral immune response of 958 individuals. Both immunoassays differentiated negative controls from endemic participants. Salivary proteins were separated by gel-electrophoresis, and antigenic proteins visualized by immunoblot. Liquid chromatography mass spectrometry (LC–MS/MS) was performed to characterize the proteome of S. damnosum s.l. salivary glands. Several antigenic proteins were recognized, with the major ones located around 15 and 40 kDa. LC–MS/MS identified the presence of antigen 5-related protein, apyrase/nucleotidase, and hyaluronidase. Conclusions/Significance This study validated for the first time human immunoassays that quantify humoral immune responses as potential markers of exposure to blackfly bites. These assays have the potential to facilitate understanding patterns of exposure as well as evaluating the impact of vector control on biting rates. Future studies need to investigate seasonal fluctuations of these antibody responses, potential cross-reactions with other bloodsucking arthropods, and thoroughly identify the most immunogenic proteins., Author summary Measuring biting rates of bloodsucking arthropods has been proved to be a crucial tool in understanding transmission dynamics and evaluating control measures against vector-borne diseases. Blackflies of the S. damnosum sensu lato (s.l.) complex are the prime vectors of Onchocerca volvulus, a filarial nematode and causative agent of human onchocerciasis (or river blindness) in Africa. Blackfly biting rates are typically measured by human attractant vector collectors who capture host-seeking female flies as they alight on their skin but before they take a blood meal. Apart from the ethical concerns raised by this method, estimates thus obtained do not reflect true exposure to vector bites. An understanding of whether there are people who receive more bites than others and who may be at higher risk of acquiring the infection is crucial to modelling control interventions. Therefore, in the present study we developed IgG- and IgM-based immunoassays to quantify antibody responses in human populations to salivary antigens of S. damnosum s.l. in onchocerciasis-endemic communities of Ghana. The proteome of S. damnosum s.l. salivary glands was also investigated to potentially identify salivary antigens that could be employed as exposure markers against this important vector group.

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. solium to support the attainment of the goals proposed in the revised World Health Organisation neglected tropical diseases roadmap for 2021-2030 adopted at the 73rd World Health Assembly in November 2020.

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 improve understanding of onchocerciasis epidemiology and disease burden estimates in the light of the WHO 2030 goals for onchocerciasis.

Taenia solium (TS), responsible for porcine cysticercosis, human taeniasis and (neuro)cysticercosis, was included in the World Health Organization neglected tropical disease (NTD) roadmap published in 2012. Targets set in this roadmap have not been met, but T. solium has been included in the consultation process for the new 2030 goals proposed for priority NTDs. Taenia solium transmission dynamics models can contribute to this process. A recent review has compared existing T. solium transmission models, identifying their similarities and differences in structure, parameterization and modelled intervention approaches. While a formal model comparison to investigate the impact of interventions is yet to be conducted, the models agree on the importance of coverage for intervention effectiveness and on the fact that human- and pig-focused interventions can be optimally combined. One of these models, cystiSim, an individual-based, stochastic model has been used to assess field-applicable interventions, some currently under evaluation in on-going trials in Zambia. The EPICYST, population-based, deterministic model has highlighted, based on simulating a generic sub-Saharan Africa setting, the higher efficacy (measured as the percentage of human cysticercosis cases prevented) of biomedical interventions (human and pig treatment and pig vaccination) compared to improved husbandry, sanitation, and meat inspection. Important questions remain regarding which strategies and combinations thereof provide sustainable solutions for severely resource-constrained endemic settings. Defining realistic timeframes to achieve feasible targets, and establishing suitable measures of effectiveness for these targets that can be quantified with current monitoring and evaluation tools, are current major barriers to identifying validated strategies. Taenia solium transmission models can support setting achievable 2030 goals; however, the refinement of these models is first required. Incorporating socio-economic elements, improved understanding of underlying biological processes, and consideration of spatial dynamics are key knowledge gaps that need addressing to support model development.

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, 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.

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., We used 2 mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings under different future treatment scenarios, including mass drug administration and vector control, assessing whether they lead to elimination of onchocerciasis.

Pan-African and country-specific (i.e. Cameroon and Democratic Republic of Congo) maps for lymphatic filariasis (LF); LF and onchocerciasis co-endemicity; LF, onchocerciasis and loiasis co-endemicity, and population estimates aggregated by African region. Text S1. Pan-African maps of lymphatic filariasis (LF). Figure S1. Pan-African map of LF endemicity at the level of implementation units (IU). Figure S2. Pan-African map of co-endemic areas for LF and onchocerciasis. Figure S3. Map of loiasis, LF and onchocerciasis co-endemicity in eastern Cameroon. Figure S4. Map of loiasis, LF and onchocerciasis co-endemicity in Oriental province, DRC. Table S1. Estimates of population living in endemic areas for lymphatic filariasis (LF) and/or onchocerciasis (oncho). Table S2. Population estimates for co-endemic areas of lymphatic filariasis, onchocerciasis and high prevalence of loiasis. (DOCX 2183 kb)

Background Onchocerciasis and lymphatic filariasis (LF) are major filarial infections targeted for elimination in most endemic sub-Saharan Africa (SSA) countries by 2020/2025. The current control strategies are built upon community-directed mass administration of ivermectin (CDTI) for onchocerciasis, and ivermectin plus albendazole for LF, with evidence pointing towards the potential for novel drug regimens. When distributing microfilaricides however, considerable care is needed to minimise the risk of severe adverse events (SAEs) in areas that are co-endemic for onchocerciasis or LF and loiasis. This work aims to combine previously published predictive risk maps for onchocerciasis, LF and loiasis to (i) explore the scale of spatial heterogeneity in co-distributions, (ii) delineate target populations for different treatment strategies, and (iii) quantify populations at risk of SAEs across the continent. Methods Geographical co-endemicity of filarial infections prior to the implementation of large-scale mass treatment interventions was analysed by combining a contemporary LF endemicity map with predictive prevalence maps of onchocerciasis and loiasis. Potential treatment strategies were geographically delineated according to the level of co-endemicity and estimated transmission intensity. Results In total, an estimated 251 million people live in areas of LF and/or onchocerciasis transmission in SSA, based on 2015 population estimates. Of these, 96 million live in areas co-endemic for both LF and onchocerciasis, providing opportunities for integrated control programmes, and 83 million live in LF-monoendemic areas potentially targetable for the novel ivermectin-diethylcarbamazine-albendazole (IDA) triple therapy. Only 4% of the at-risk population live in areas co-endemic with high loiasis transmission, representing up to 1.2 million individuals at high risk of experiencing SAEs if treated with ivermectin. In these areas, alternative treatment strategies should be explored, including biannual albendazole monotherapy for LF (1.4 million individuals) and ‘test-and-treat’ strategies (8.7 million individuals) for onchocerciasis. Conclusions These maps are intended to initiate discussion around the potential for tailored treatment strategies, and highlight populations at risk of SAEs. Further work is required to test and refine strategies in programmatic settings, providing the empirical evidence needed to guide efforts towards the 2020/2025 goals and beyond. Electronic supplementary material The online version of this article (10.1186/s13071-018-2655-5) contains supplementary material, which is available to authorized users.

Table S1. Environmental data summary. Table S2. Correlation coefficients for NDVI and LST, 2007–2011. Table S3. Model validation results, mean prediction error, absolute prediction error and Pearson’s correlation coefficient for all parasites, 2008–2011 and 2014. Table S4. Average size of clusters and propensity of clustering per parasite per year. Table S5. Model effect sizes for all parasites, 2008–2011 and 2014. Table S6. Total number of infected children per year per parasite 2008–2011 and 2014. Figure S1. Residual semivariograms for prevalence of infection with Ascaris lumbricoides in Burundi for years 2007–2011 and 2014. Figure S2. Residual semivariograms for prevalence of infection with Trichuris trichiura in Burundi for years 2007–2011 and 2014. Figure S3. Residual semivariograms for prevalence of infection with hookworm in Burundi for years 2007–2011 and 2014. Figure S4. Posterior mean standard deviation of predicted prevalence of infection with Ascaris lumbricoides in Burundi for 2008–2011 and 2014. Figure S5. Posterior mean standard deviation of predicted prevalence of infection with Trichuris trichiura in Burundi for 2008–2011 and 2014. Figure S6. Posterior mean standard deviation of predicted prevalence of infection with hookworm in Burundi for 2008–2011 and 2014. (DOCX 761 kb)

Table S1. Sample sizes and numbers of pupils followed up by year for the impact study conducted in Burundi from 2007 to 2011. Figure S1. Semivariograms representing the prevalence of Ascaris lumbricoides and Trichuris trichiura coinfection from 2007 to 2011. Figure S2. Variation in temporal patterns of prevalence change across pilot study sentinel sites in Burundi between 2007 and 2011, and in 2014 based on the models presented in Table 4. Figure S3. Variation in temporal patterns of prevalence change across extension study sentinel sites in Burundi between 2007 and 2011, and in 2014 based on the models presented in Table 5. Figure S4. Semivariograms representing the prevalence of low infection intensity from 2007 to 2014 for Ascaris lumbricoides. Figure S5. Semivariograms representing the prevalence of moderate infection intensity from 2007 to 2014 for Ascaris lumbricoides. Figure S6. Semivariograms representing the prevalence of low infection intensity from 2007 to 2014 for Trichuris trichiura. Figure S7. Semivariograms representing the prevalence of low infection intensity from 2007 to 2014 for hookworm. (DOCX 3548 kb)

Markov model equations, model parameters and additional tables and figures. Text S1. Markov model formulae. Table S1. Definition of parameters for the Markov Model. Table S2. Uganda subset information for dataset 2 and matrix C. Figure S1. Results from applying transition probability (TP) matrices B and C on dataset 1 (full longitudinal Uganda data set). Figure S2. Results from applying TP matrices A–C on dataset 2 (selected Ugandan districts). Figure S3. Results from applying TP matrices B and C on dataset 3 (cross-sectional Ugandan dataset). Figure S4. Results from applying TP matrix D (baseline and year 1 Mali data for TPs) on dataset 4 (longitudinal Mali dataset). (DOC 6719 kb)

Additional figures illustrating setting-specific sensitivity and the influence of microfilarial overdispersion. Figure S1. Sensitivity of the skin snip method in the Amazonian focus of southern Venezuela. Figure S2. Sensitivity of the skin snip method in the Volta region of Ghana. Figure S3. Sensitivity of the skin snip method under different scenarios for the amount of microfilarial aggregation. (PDF 421 kb)

Additional figures illustrating setting-specific sensitivity and the influence of microfilarial overdispersion. Figure S1. Sensitivity of the skin snip method in the Amazonian focus of southern Venezuela. Figure S2. Sensitivity of the skin snip method in the Volta region of Ghana. Figure S3. Sensitivity of the skin snip method under different scenarios for the amount of microfilarial aggregation. (PDF 421 kb)

Supplementary Methods, Figures and Tables. (DOCX 108 kb)

Supplementary Methods, Figures and Tables. (DOCX 108 kb)