257 results found
Dixon-Zegeye M, Winskill P, Harrison W, et al., 2022, Global force-of-infection trends for human taenia solium taeniasis/cysticercosis, eLife, Vol: 11, ISSN: 2050-084X
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 setting43 specific intervention strategies to achieve the WHO goals.
Tirados I, Thomsen E, Worrall E, et al., 2022, Vector control and entomological capacity for onchocerciasis elimination, Trends in Parasitology, Vol: 38, Pages: 591-604, ISSN: 0169-4758
Mass drug administration (MDA) of ivermectin is currently the main strategy to achieve elimination of onchocerciasis transmission (EoT). Modelling suggests that EoT may not be reached in all endemic foci using annual MDA alone. Onchocerciasis and loiasis are co endemic in forest areas of Central Africa, where ivermectin treatment can lead to severe adverse events in individuals with heavy loiasis load, rendering MDA inappropriate. Vector control has been proposed as a complementary intervention strategy. Here, we discuss: (i) achievements and pitfalls of previous interventions; (ii) epidemiological impact, feasibility and combination with MDA to accelerate and/or protect EoT; (iii) role of modelling; (iv) opportunities for innovative methods of vector monitoring and control, and (v) strengthening entomological capacity in endemic countries.
Widdicombe J, Basáñez M-G, Entezami M, et al., 2022, The economic evaluation of Cystic echinococcosis control strategies focused on zoonotic hosts: A scoping review., PLoS Negl Trop Dis, Vol: 16
BACKGROUND: Cystic echinococcosis (CE) is a zoonotic neglected tropical disease (zNTD) which imposes considerable financial burden to endemic countries. The 2021-2030 World Health Organization's roadmap on NTDs has proposed that intensified control be achieved in hyperendemic areas of 17 countries by 2030. Successful interventions for disease control, and the scale-up of programmes applying such interventions, rely on understanding the associated costs and relative return for investment. We conducted a scoping review of existing peer-reviewed literature on economic evaluations of CE control strategies focused on Echinococcus granulosus zoonotic hosts. METHODOLOGY/PRINCIPAL FINDINGS: Database searches of Scopus, PubMed, Web of Science, CABI Direct and JSTOR were conducted and comprehensively reviewed in March 2022, using predefined search criteria with no date, field or language restrictions. A total of 100 papers were initially identified and assessed for eligibility against strict inclusion and exclusion criteria, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Bibliography review of included manuscripts was used to identify additional literature. Full review of the final manuscript selection (n = 9) was performed and cost data for control interventions were extracted. CONCLUSIONS/SIGNIFICANCE: There are very little published data pertaining to the cost and cost effectiveness of CE control interventions targeting its zoonotic hosts. Data given for costs are often incomplete, thus we were unable to perform an economic analysis and cost effectiveness study, highlighting a pressing need for this information. There is much scope for future work in this area. More detailed information and disaggregated costings need to be collected and made available. This would increase the accuracy of any cost-effective analyses to be performed and allow for a greater understanding of the opportuni
Ledien J, Cucunubá ZM, Parra-Henao G, et al., 2022, Linear and Machine Learning modelling for spatiotemporal disease predictions: Force-of-Infection of Chagas disease., PLoS Negl Trop Dis, Vol: 16
BACKGROUND: Chagas disease is a long-lasting disease with a prolonged asymptomatic period. Cumulative indices of infection such as prevalence do not shed light on the current epidemiological situation, as they integrate infection over long periods. Instead, metrics such as the Force-of-Infection (FoI) provide information about the rate at which susceptible people become infected and permit sharper inference about temporal changes in infection rates. FoI is estimated by fitting (catalytic) models to available age-stratified serological (ground-truth) data. Predictive FoI modelling frameworks are then used to understand spatial and temporal trends indicative of heterogeneity in transmission and changes effected by control interventions. Ideally, these frameworks should be able to propagate uncertainty and handle spatiotemporal issues. METHODOLOGY/PRINCIPAL FINDINGS: We compare three methods in their ability to propagate uncertainty and provide reliable estimates of FoI for Chagas disease in Colombia as a case study: two Machine Learning (ML) methods (Boosted Regression Trees (BRT) and Random Forest (RF)), and a Linear Model (LM) framework that we had developed previously. Our analyses show consistent results between the three modelling methods under scrutiny. The predictors (explanatory variables) selected, as well as the location of the most uncertain FoI values, were coherent across frameworks. RF was faster than BRT and LM, and provided estimates with fewer extreme values when extrapolating to areas where no ground-truth data were available. However, BRT and RF were less efficient at propagating uncertainty. CONCLUSIONS/SIGNIFICANCE: The choice of FoI predictive models will depend on the objectives of the analysis. ML methods will help characterise the mean behaviour of the estimates, while LM will provide insight into the uncertainty surrounding such estimates. Our approach can be extended to the modelling of FoI patterns in other Chagas disease-endemic countries
Poggio TV, Gómez JM, Boado LA, et al., 2022, Immunodiagnosis of cystic echinococcosis in livestock: Development and validation dataset of an ELISA test using a recombinant B8/2 subunit of Echinococcus granulosus sensu lato, Data in Brief, Vol: 42, ISSN: 2352-3409
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
Sykes AL, Larrieu E, Poggio TV, et al., 2022, Modelling diagnostics for echinococcus granulosus surveillance in sheep using latent class analysis: Argentina as a case study, One Health, Vol: 14, Pages: 1-7, ISSN: 2352-7714
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 surveillan
Colebunders R, Kaiser C, Basanez M-G, et al., 2022, Reducing onchocerciasis-associated morbidity in onchocerciasis-endemic foci with high ongoing transmission: a focus on the children, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 116, Pages: 302-305, ISSN: 1201-9712
Ledien J, Cucunuba ZM, Parra-Henao G, et al., 2022, Spatiotemporal variations in exposure: Chagas disease in Colombia as a case study, BMC Medical Research Methodology, Vol: 22, Pages: 1-12, ISSN: 1471-2288
Age-stratified serosurvey data are often used to understand spatiotemporal trends in disease incidence and exposure through estimating the Force-of-Infection (FoI). Typically, median or mean FoI estimates are used as the response variable in predictive models, often overlooking the uncertainty in estimated FoI values when fitting models and evaluating their predictive ability. To assess how this uncertainty impact predictions, we compared three approaches with three levels of uncertainty integration. We propose a performance indicator to assess how predictions reflect initial uncertainty.In Colombia, 76 serosurveys (1980–2014) conducted at municipality level provided age-stratified Chagas disease prevalence data. The yearly FoI was estimated at the serosurvey level using a time-varying catalytic model. Environmental, demographic and entomological predictors were used to fit and predict the FoI at municipality level from 1980 to 2010 across Colombia.A stratified bootstrap method was used to fit the models without temporal autocorrelation at the serosurvey level. The predictive ability of each model was evaluated to select the best-fit models within urban, rural and (Amerindian) indigenous settings. Model averaging, with the 10 best-fit models identified, was used to generate predictions.Our analysis shows a risk of overconfidence in model predictions when median estimates of FoI alone are used to fit and evaluate models, failing to account for uncertainty in FoI estimates. Our proposed methodology fully propagates uncertainty in the estimated FoI onto the generated predictions, providing realistic assessments of both central tendency and current uncertainty surrounding exposure to Chagas disease.
Willen L, Milton P, Hamley JID, et al., 2022, Demographic patterns of human antibody levels to Simulium damnosum s.l. saliva in onchocerciasis-endemic areas: An indicator of exposure to vector bites, PLoS Neglected Tropical Diseases, Vol: 16, ISSN: 1935-2727
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.
Walker M, Freitas LT, Halder JB, et al., 2022, Improving anthelmintic treatment for schistosomiasis and soil-transmitted helminthiases through sharing and reuse of individual participant data., Wellcome Open Res, Vol: 7, ISSN: 2398-502X
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.
Retkute R, Touloupou P, Basanez M-G, et al., 2021, Integrating geostatistical maps and infectious disease transmission models using Adaptive Multiple Importance Sampling, Annals of Applied Statistics, Vol: 15, Pages: 1980-1998, ISSN: 1932-6157
The Adaptive Multiple Importance Sampling algorithm (AMIS)is an iterative technique which recycles samples from all previousiterations in order to improve the efficiency of the proposal distribution. We have formulated a new statistical framework, based onAMIS, to take the output from a geostatistical model of infectiousdisease prevalence, incidence or relative risk, and project it forwardin time under a mathematical model for transmission dynamics. Weadapted the AMIS algorithm so that it can sample from multiple targets simultaneously by changing the focus of the adaptation at eachiteration. By comparing our approach against the standard AMIS algorithm, we showed that these novel adaptations greatly improve theefficiency of the sampling. We tested the performance of our algorithmon four case studies: ascariasis in Ethiopia, onchocerciasis in Togo,human immunodeficiency virus (HIV) in Botswana, and malaria inthe Democratic Republic of the Congo.
Galipó E, Dixon-Zegeye M, Fronterrè C, et al., 2021, Spatial distribution and risk factors for human cysticercosis in Colombia, Parasites and Vectors, Vol: 14, Pages: 1-15, ISSN: 1756-3305
BackgroundCysticercosis is a zoonotic neglected tropical disease (NTD) that affects humans and pigs following the ingestion of Taenia solium eggs. Human cysticercosis poses a substantial public health burden in endemic countries. The World Health Organization (WHO) aims to target high-endemicity settings with enhanced interventions in 17 countries by 2030. Between 2008 and 2010, Colombia undertook a national baseline serosurvey of unprecedented scale, which led to an estimated seroprevalence of T. solium cysticercus antibodies among the general population of 8.6%. Here, we use contemporary geostatistical approaches to analyse this unique dataset with the aim of understanding the spatial distribution and risk factors associated with human cysticercosis in Colombia to inform how best to target intervention strategies.MethodsWe used a geostatistical model to estimate individual and household risk factors associated with seropositivity to T. solium cysticercus antibodies from 29,253 people from 133 municipalities in Colombia. We used both independent and spatially structured random effects at neighbourhood/village and municipality levels to account for potential clustering of exposure to T. solium. We present estimates of the distribution and residual correlation of seropositivity at the municipality level.ResultsHigh seroprevalence was identified in municipalities located in the north and south of Colombia, with spatial correlation in seropositivity estimated up to approximately 140 km. Statistically significant risk factors associated with seropositivity to T. solium cysticercus were related to age, sex, educational level, socioeconomic status, use of rainwater, consumption of partially cooked/raw pork meat and possession of dogs.ConclusionsIn Colombia, the distribution of human cysticercosis is influenced by socioeconomic considerations, education and environmental factors related to the spread of T. solium eggs. This information can be used to tailor national interv
Jewell PD, Abraham A, Schmidt V, et al., 2021, Neurocysticercosis and HIV/AIDS co-infection: a scoping review, Tropical Medicine and International Health, Vol: 26, Pages: 1140-1152, 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.
Walker M, Hamley J, Milton P, et al., 2021, Supporting drug development for neglected tropical diseases using mathematical modelling, Clinical Infectious Diseases, Vol: 73, Pages: e1391-e1396, 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.
Siewe Fodjo JN, Vieri MK, Ngarka L, et al., 2021, 'Slash and clear' vector control for onchocerciasis elimination and epilepsy prevention: a protocol of a cluster randomised trial in Cameroonian villages., BMJ Open, Vol: 11, Pages: 1-10, ISSN: 2044-6055
INTRODUCTION: Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, remains endemic in Cameroon despite decades of community-directed treatment with ivermectin (CDTI). CDTI is often hampered by coendemicity with loiasis (another filariasis caused by Loa loa) in some areas. Strong epidemiological evidence suggests that O. volvulus infection increases the risk for onchocerciasis-associated epilepsy (OAE) among Cameroonian children. This highlights the urgent need to strengthen onchocerciasis elimination programmes in mesoendemic/hyperendemic areas. Novel alternative strategies, such as the 'slash and clear' (S&C) vector control method, may be required to complement ongoing CDTI to accelerate elimination of transmission. The short-term impact of S&C on the biting rates of the blackfly vectors has been demonstrated in other settings. However, its long-term effectiveness and impact on parasitological and serological markers of onchocerciasis transmission as well as on OAE are still unknown. METHODS AND ANALYSIS: We aim to assess the effectiveness of annual S&C interventions combined with CDTI in reducing onchocerciasis transmission and epilepsy incidence. Eight onchocerciasis-endemic villages located <5 km from the Mbam or Sanaga rivers will be randomised to two arms: four villages will receive yearly CDTI only for two consecutive years (Arm 1), while the other four villages will receive CDTI plus annual S&C for 2 years (Arm 2). Study outcomes (blackfly biting rates, infectivity rates and seroprevalence of onchocerciasis antibodies (Ov16 antibodies) in children, prevalence of microfilaridermia and epilepsy incidence) will be monitored prospectively and compared across study arms. We expect that S&C will have an added benefit over CDTI alone. ETHICS AND DISSEMINATION: The protocol has received ethical approval from the institutional review board of the Cameroon Baptist Convention Health Board (reference number: IRB2021-0
Cromwell EA, Osborne JCP, Unnasch TR, et al., 2021, Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning., PLoS Neglected Tropical Diseases, Vol: 15, Pages: 1-23, ISSN: 1935-2727
Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initia
Willen L, Basanez M-G, Dvorak V, et al., 2021, Human immune response against salivary antigens of Simulium damnosum s.l.: A new epidemiological marker for exposure to blackfly bites in onchocerciasis endemic areas, PLoS Neglected Tropical Diseases, Vol: 15, ISSN: 1935-2727
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 fluctuati
Stolk WA, Blok DJ, Hamley JID, et 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.
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
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.
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