248 results found
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
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
Ledien J, Cucunuba ZM, Parra-Henao G, et al., 2021, Spatiotemporal variations in exposure: Chagas disease in Colombia as a case study, BMC Medical Research Methodology, 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.
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.
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, 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.
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., Pages: 1-50
Onchocerciasis (also known as 'river blindness'), is a neglected tropical disease (NTD) caused by the (Simulium-transmitted) filarial nematode Onchocerca volvulus. The occurrence of 'blinding' (savannah) and non-blinding (forest) parasite strains and the existence of corresponding, locally adapted Onchocerca-Simulium complexes were postulated to explain greater blindness prevalence in savannah than in forest foci. As a result, the World Health Organization (WHO) Onchocerciasis Control Programme in West Africa (OCP) focused anti-vectorial and anti-parasitic interventions in savannah endemic areas. In this paper, village-level data on blindness prevalence, microfilarial prevalence, and transmission intensity (measured by the annual transmission potential, the number of infective, L3, larvae per person per year) were extracted from 16 West-Central Africa-based publications, and analysed according to habitat (forest, forest-savannah mosaic, savannah) to test the dichotomous strain hypothesis in relation to blindness. When adjusting for sample size, there were no statistically significant differences in blindness prevalence between the habitats (one-way ANOVA, P=0.68, mean prevalence for forest=1.76±0.37 (SE); mosaic=1.49±0.38; savannah=1.89±0.26). The well-known relationship between blindness prevalence and annual transmission potential for savannah habitats was confirmed and shown to hold for (but not to be statistically different from) forest foci (excluding data from southern Côte d'Ivoire, in which blindness prevalence was significantly lower than in other West African forest communities, but which had been the focus of studies leading to the strain-blindness hypothesis that was accepted by OCP planners). We conclude that the evidence for a savannah blinding onchocerciasis strain in simple contrast with a non-blinding forest strain is equivocal. A re-appraisal of the strain hypothesis to explain patterns of ocular disease is needed to impr
Dolo H, Coulibaly YI, Sow M, et al., 2020, Serological evaluation of onchocerciasis and lymphatic filariasis elimination in the Bakoye and Faleme foci, Mali, Publisher: ELSEVIER SCI LTD, Pages: 427-428, ISSN: 1201-9712
Dixon MA, Winskill P, Harrison W, et al., 2020, Force-of-Infection of Taenia solium porcine cysticercosis: a modelling analysis to assess global incidence and prevalence trends, Scientific Reports, Vol: 10, ISSN: 2045-2322
The World Health Organization (WHO) called, in 2012, for a validated strategy towards Taenia solium taeniasis/cysticercosis control and elimination. Estimating pig force-of-infection (FoI, the average rate at which susceptible pigs become infected) across geographical settings will help understand local epidemiology and inform effective intervention design. Porcine cysticercosis (PCC) age-prevalence data (from 15 studies in Latin America, Africa and Asia) were identified through systematic review. Catalytic models were fitted to the data using Bayesian methods, incorporating uncertainty in diagnostic performance, to estimate rates of antibody seroconversion, viable metacestode acquisition, and seroreversion/infection loss. There was evidence of antibody seroreversion across 5 studies, and of infection loss in 6 studies measured by antigen or necropsy, indicating transient serological responses and natural resolution of infection. Concerted efforts should be made to collect robust data using improved diagnostics to better understand geographical heterogeneities in T. solium transmission to support post-2020 WHO targets.
Basanez M-G, Milton P, Hamley J, et al., 2020, Moxidectin: an oral treatment for human onchocerciasis, Expert Review of Anti-infective Therapy, Vol: 18, Pages: 1067-1081, ISSN: 1478-7210
Introduction: Moxidectin is a milbemycin endectocide recently approved for the treatment of humanonchocerciasis. Onchocerciasis, earmarked for elimination of transmission, is a filarial infection endemicin Africa, Yemen, and the Amazonian focus straddling Venezuela and Brazil. Concerns over whether thepredominant treatment strategy (yearly mass drug administration (MDA) of ivermectin) is sufficient toachieve elimination in all endemic foci have refocussed attention upon alternative treatments.Moxidectin’s stronger and longer microfilarial suppression compared to ivermectin in both phase IIand III clinical trials indicates its potential as a novel powerful drug for onchocerciasis elimination.Areas covered: This work summarizes the chemistry and pharmacology of moxidectin, reviews thephase II and III clinical trials evidence on tolerability, safety, and efficacy of moxidectin versus ivermectin, and discusses the implications of moxidectin’s current regulatory status.Expert opinion: Moxidectin’s superior clinical performance has the potential to substantially reducetimes to elimination compared to ivermectin. If donated, moxidectin could mitigate the additionalprogrammatic costs of biannual ivermectin distribution because, unlike other alternatives, it can use theexisting community-directed treatment infrastructure. A pediatric indication (for children <12 years) anddetermination of its usefulness in onchocerciasis–loiasis co-endemic areas will greatly help fulfill thepotential of moxidectin for the treatment and elimination of onchocerciasis.
Hamley J, Walker M, Coffeng LE, et al., 2020, Structural uncertainty in onchocerciasis transmission models influences the estimation of elimination thresholds and selection of age groups for seromonitoring, Journal of Infectious Diseases, Vol: 221, Pages: S510-S518, ISSN: 0022-1899
Background. The World Health Organization recommends monitoring Ov16 serologyin children aged <10 years for stopping mass ivermectin administration. Transmission models can help to identify the most informative age groups for serological monitoring and investigate the discriminatory power of serology-based elimination thresholds.Model predictions will depend on assumed age-exposure patterns and transmission efficiency at low infection levels. Methods. The individual-based transmission model, EPIONCHO-IBM, was used toassess: i) the most informative age groups for serological monitoring using receiveroperator characteristic curves for different elimination thresholds under various age-dependent exposure assumptions, including those of ONCHOSIM (another widely-used model), and ii) the influence of within-human density-dependent parasite establishment (included in EPIONCHO-IBM but not in ONCHOSIM) on positive predictive values for different serological thresholds.Results. When assuming EPIONCHO-IBM exposure patterns, under-10s are themost informative age group for seromonitoring; when assuming ONCHOSIM’s exposure patterns, 5–15-year olds are the most informative (as published elsewhere).Omitting density-dependent parasite establishment results in more lenientseroprevalence thresholds, even for higher baseline infection prevalence and shorter treatment durations.Conclusions. Selecting appropriate seromonitoring age groups depends critically onage-dependent exposure patterns. The role of density dependence on elimination thresholds largely explains differing EPIONCHO-IBM and ONCHOSIM elimination predictions.
Walker M, Hamley JID, Milton P, et al., 2020, Designing antifilarial drug trials using clinical trial simulators, Nature Communications, Vol: 11, Pages: 1-11, ISSN: 2041-1723
Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.
Behrend M, Basanez M-G, Hamley JID, et al., 2020, Modelling for policy: the five principles of the Neglected Tropical Diseases Modelling Consortium, PLoS Neglected Tropical Diseases, ISSN: 1935-2727
Nana Djeunga H, Domche A, Niamsi-Emalio Y, et al., 2020, Situation analysis of onchocerciasis in Cameroon: a protocol for systematic review of epidemiological studies and impact of disease control interventions, Systematic Reviews, ISSN: 2046-4053
Dixon M, Braae UC, Winskill P, et al., 2020, Modelling for Taenia solium control strategies beyond 2020, Bulletin of the World Health Organization, Vol: 98, Pages: 198-205, ISSN: 0042-9686
The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. soliumtransmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies.
Kim JYH, Ledien J, Rodriguez-Monguí E, et al., 2019, Global Trends of Seroprevalence and Universal Screening Policy for Chagas Disease in Donors: a systematic review and meta-analysis, medRxiv
<h4>Background</h4> Screening for Trypanosoma cruzi among blood and organ donors is essential to reduce Chagas disease transmission. The World Health Organization (WHO) has prioritised curtailing transmission in blood banks (BBs) and transplantation centres (TCs) by 50% by 2025 and 100% by 2030. This study aims to update the situation on T. cruzi screening strategies in BBs and TCs to evaluate the evolution of seroprevalence and the achievement of screening milestones globally. <h4>Methods</h4> We used published articles and government reports on seroprevalence data and screening policies in BBs and TCs across the world. We conducted meta-analyses of T. cruzi seroprevalence estimates by who region, endemicity status, and country, and used meta-regression to identify the covariates influencing the estimates. Publication bias and sensitivity analyses were also conducted. <h4>Results</h4> Based on 99 studies and reports and found a global pattern of increased universal screening policies (USPs) in BBs from 1990 to 2018. We found information for 50 countries, of which 44 (88%) have implemented USPs and 21 (42%) achieved 100% coverage by 2015. Out of the 21 Chagas-disease endemic countries, 20 are in advanced USPS stages, and 18 achieved 100% coverage by 2015. Latin America (LA) was the first region to start USPS since the 1990s and 19 countries are in advanced stages of implementation and by 2015 there is evidence of 100% coverage in 15 LA countries. In the Caribbean Region, USPs are still in early implementation stages and by 2015 only five out of 24 countries have achieved 100% coverage. Outside Latin America and the Caribbean, there are USPs only in the USA, which initiated in 2007 and with 100% coverage in 2016. In Europe, there are no USPs, but some countries have implemented selective screening of at-risk donors in the UK, Spain, France and Switzerland. Whereas Sweden and Italy have implemented a deferral system. For TCs, nation
Deol AK, Fleming FM, Calvo-Urbano B, et al., 2019, Schistosomiasis — assessing progress toward the 2020 and 2025 global goals, New England Journal of Medicine, Vol: 381, Pages: 2519-2528, ISSN: 0028-4793
BackgroundWith the vision of “a world free of schistosomiasis,” the World Health Organization (WHO) set ambitious goals of control of this debilitating disease and its elimination as a public health problem by 2020 and 2025, respectively. As these milestones become imminent, and if programs are to succeed, it is important to evaluate the WHO programmatic guidelines empirically.MethodsWe collated and analyzed multiyear cross-sectional data from nine national schistosomiasis control programs (in eight countries in sub-Saharan Africa and in Yemen). Data were analyzed according to schistosome species (Schistosoma mansoni or S. haematobium), number of treatment rounds, overall prevalence, and prevalence of heavy-intensity infection. Disease control was defined as a prevalence of heavy-intensity infection of less than 5% aggregated across sentinel sites, and the elimination target was defined as a prevalence of heavy-intensity infection of less than 1% in all sentinel sites. Heavy-intensity infection was defined as at least 400 eggs per gram of feces for S. mansoni infection or as more than 50 eggs per 10 ml of urine for S. haematobium infection.ResultsAll but one country program (Niger) reached the disease-control target by two treatment rounds or less, which is earlier than projected by current WHO guidelines (5 to 10 years). Programs in areas with low endemicity levels at baseline were more likely to reach both the control and elimination targets than were programs in areas with moderate and high endemicity levels at baseline, although the elimination target was reached only for S. mansoni infection (in Burkina Faso, Burundi, and Rwanda within three treatment rounds). Intracountry variation was evident in the relationships between overall prevalence and heavy-intensity infection (stratified according to treatment rounds), a finding that highlights the challenges of using one metric to define control or elimination across all epidemiologic settings.Conclusio
Hamley JID, Milton P, Walker M, et al., 2019, Modelling exposure heterogeneity and density dependence in onchocerciasis using a novel individual-based transmission model, EPIONCHO-IBM: Implications for elimination and data needs, PLoS Neglected Tropical Diseases, Vol: 13, Pages: e0007557-e0007557, ISSN: 1935-2727
BackgroundDensity dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin.Methodology/Principal findingsDensity dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d’Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model.Conclusions/SignificanceThis is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improvin
Buell KG, Whittaker C, Chesnais CB, et al., 2019, Atypical clinical manifestations of Loiasis and their relevance for endemic populations, Open Forum Infectious Diseases, Vol: 6, ISSN: 2328-8957
Background: Loiasis is mostly considered a relatively benign infection when compared with other filarial and parasitic diseases, with Calabar swellings and eyeworm being the most common signs. Yet, there are numerous reports in the literature of more serious sequelae. Establishing the relationship between infection and disease is a crucial first step toward estimating the burden of loiasis. Methods: We conducted a systematic review of case reports containing 329 individuals and detailing clinical manifestations of loiasis with a focus on nonclassical, atypical presentations. Results: Results indicate a high proportion (47%) of atypical presentations in the case reports identified, encompassing a wide range of cardiac, respiratory, gastrointestinal, renal, neurological, ophthalmological, and dermatological pathologies. Individuals with high microfilarial densities and residing in an endemic country were at greater risk of suffering from atypical manifestations. Conclusions: Our findings have important implications for understanding the clinical spectrum of conditions associated with Loa loa infection, which extends well beyond the classical eyeworm and Calabar swellings. As case reports may overestimate the true rate of atypical manifestations in endemic populations, large-scale, longitudinal clinico-epidemiological studies will be required to refine our estimates and demonstrate causality between loiasis and the breadth of clinical manifestations reported. Even if the rates of atypical presentations were found to be lower, given that residents of loiasis-endemic areas are both numerous and the group most at risk of severe atypical manifestations, our conclusions support the recognition of loiasis as a significant public health burden across Central Africa.
Fodjo SJN, Menon S, Hotterbeekx A, et al., 2019, ONCHOCERCIASIS-ASSOCIATED EPILEPSY: THE EPIDEMIOLOGICAL EVIDENCE, Publisher: OXFORD UNIV PRESS, Pages: S56-S56, ISSN: 0035-9203
Fodjo SJN, Menon S, Hotterbeekx A, et al., 2019, ONCHOCERCIASIS-ASSOCIATED EPILEPSY: THE EPIDEMIOLOGICAL EVIDENCE, Publisher: OXFORD UNIV PRESS, Pages: S58-S59, ISSN: 0035-9203
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.