562 results found
Kura K, Ayabina D, Hollingsworth TD, et al., 2022, Determining the optimal strategies to achieve elimination of transmission for Schistosoma mansoni, PARASITES & VECTORS, Vol: 15, ISSN: 1756-3305
Landeryou T, Rabone M, Allan F, et al., 2022, Genome-wide insights into adaptive hybridisation across the Schistosoma haematobium group in West and Central Africa., PLoS Negl Trop Dis, Vol: 16
Schistosomiasis remains a public health concern across sub-Saharan Africa; current control programmes rely on accurate mapping and high mass drug administration (MDA) coverage to attempt disease elimination. Inter-species hybridisation can occur between certain species, changing epidemiological dynamics within endemic regions, which has the potential to confound control interventions. The impact of hybridisation on disease dynamics is well illustrated in areas of Cameroon where urogenital schistosomiasis, primarily due to Schistosoma haematobium and hybrid infections, now predominate over intestinal schistosomiasis caused by Schistosoma guineensis. Genetic markers have shown the ability to identify hybrids, however the underlying genomic architecture of divergence and introgression between these species has yet to be established. In this study, restriction site associated DNA sequencing (RADseq) was used on archived adult worms initially identified as; Schistosoma bovis (n = 4), S. haematobium (n = 9), S. guineensis (n = 3) and S. guineensis x S. haematobium hybrids (n = 4) from Mali, Senegal, Niger, São Tomé and Cameroon. Genome-wide evidence supports the existence of S. guineensis and S. haematobium hybrid populations across Cameroon. The hybridisation of S. guineensis x S. haematobium has not been demonstrated on the island of São Tomé, where all samples showed no introgression with S. haematobium. Additionally, all S. haematobium isolates from Nigeria, Mali and Cameroon indicated signatures of genomic introgression from S. bovis. Adaptive loci across the S. haematobium group showed that voltage-gated calcium ion channels (Cav) could play a key role in the ability to increase the survivability of species, particularly in host systems. Where admixture has occurred between S. guineensis and S. haematobium, the excess introgressive influx of tegumental (outer helminth body) and antigenic genes from S. haematobium has increased the adaptiv
Kura K, Hardwick RJ, Truscott JE, et al., 2021, What is the impact of acquired immunity on the transmission of schistosomiasis and the efficacy of current and planned mass drug administration programmes?, PLoS Neglected Tropical Diseases, Vol: 15, Pages: 1-17, ISSN: 1935-2727
Schistosomiasis causes severe morbidity in many countries with endemic infection with the schistosome digenean parasites in Africa and Asia. To control and eliminate the disease resulting from infection, regular mass drug administration (MDA) is used, with a focus on school-aged children (SAC; 5-14 years of age). In some high transmission settings, the World Health Organization (WHO) also recommends the inclusion of at-risk adults in MDA treatment programmes. The question of whether ecology (age-dependant exposure) or immunity (resistance to reinfection), or some combination of both, determines the form of observed convex age-intensity profile is still unresolved, but there is a growing body of evidence that the human hosts acquire some partial level of immunity after a long period of repeated exposure to infection. In the majority of past research modelling schistosome transmission and the impact of MDA programmes, the effect of acquired immunity has not been taken into account. Past work has been based on the assumption that age-related contact rates generate convex horizontal age-intensity profiles. In this paper, we use an individual based stochastic model of transmission and MDA impact to explore the effect of acquired immunity in defined MDA programmes. Compared with scenarios with no immunity, we find that acquired immunity makes the MDA programme less effective with a slower decrease in the prevalence of infection. Therefore, the time to achieve morbidity control and elimination as a public health problem is longer than predicted by models with just age-related exposure and no build-up of immunity. The level of impact depends on the baseline prevalence prior to treatment (the magnitude of the basic reproductive number R0) and the treatment frequency, among other factors. We find that immunity has a larger impact within moderate to high transmission settings such that it is very unlikely to achieve morbidity and transmission control employing current MDA prog
Milne G, Hames T, Scotton C, et al., 2021, Does infection with or vaccination against SARS-CoV-2 lead to lasting immunity?, LANCET RESPIRATORY MEDICINE, Vol: 9, Pages: 1450-1466, ISSN: 2213-2600
Anderson RM, 2021, An urgent need: vaccines for neglected tropical diseases, LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 1621-1623, ISSN: 1473-3099
Anderson RM, Vegvari C, Hollingsworth TD, et al., 2021, The SARS-CoV-2 pandemic: remaining uncertainties in our understanding of the epidemiology and transmission dynamics of the virus, and challenges to be overcome, INTERFACE FOCUS, Vol: 11, ISSN: 2042-8898
Lochen A, Anderson RM, 2021, Dynamic transmission models and economic evaluations of pneumococcal conjugate vaccines: a quality appraisal and limitations (vol 26, pg 60, 2020), CLINICAL MICROBIOLOGY AND INFECTION, Vol: 27, Pages: 1545-1545, ISSN: 1198-743X
Lochen A, Anderson RM, 2021, Dynamic transmission models and economic evaluations of pneumococcal conjugate vaccines: a quality appraisal and limitations, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 27, Pages: 1546-1557, ISSN: 1198-743X
Chong NS, Smith SR, Werkman M, et al., 2021, Modelling the ability of mass drug administration to interrupt soil-transmitted helminth transmission: Community-based deworming in Kenya as a case study, PLOS NEGLECTED TROPICAL DISEASES, Vol: 15, ISSN: 1935-2735
Papaiakovou M, Littlewood TJ, Gasser RB, et al., 2021, How qPCR complements the WHO roadmap (2021-2030) for soil-transmitted helminths, TRENDS IN PARASITOLOGY, Vol: 37, Pages: 698-708, ISSN: 1471-4922
Ayabina D, Kura K, Toor J, et al., 2021, Maintaining low prevalence of Schistosoma mansoni: modelling the effect of less frequent treatment, Clinical Infectious Diseases, Vol: 72, Pages: S140-S145, ISSN: 1058-4838
BACKGROUND: The World Health Organization (WHO) previously set goals of controlling morbidity due to schistosomiasis by 2020 and attaining elimination as a public health problem (EPHP) by 2025 (now adjusted to 2030 in the new neglected tropical diseases roadmap). As these milestones are reached, it is important that programs reassess their treatment strategies to either maintain these goals or progress from morbidity control to EPHP and ultimately to interruption of transmission. In this study, we consider different mass drug administration (MDA) strategies to maintain the goals. METHODS: We use two independently developed individual-based stochastic models of schistosomiasis transmission to assess the optimal treatment strategy of a multi-year program to maintain the morbidity control and the EPHP goals. RESULTS: We find that in moderate prevalence settings, once the morbidity control and EPHP goals are reached, it may be possible to maintain the goals using less frequent MDAs than those that are required to achieve the goals. On the other hand, in some high transmission settings, if control efforts are reduced after achieving the goals, particularly the morbidity control goal, there is a high chance of recrudescence. CONCLUSIONS: To reduce the risk of recrudescence after the goals are achieved, programs have to re-evaluate their strategies and decide to either maintain these goals with reduced efforts where feasible or continue with at least the same efforts required to reach the goals.
Vegvari C, Giardina F, Malizia V, et al., 2021, Impact of Key Assumptions About the Population Biology of Soil-Transmitted Helminths on the Sustainable Control of Morbidity, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: S188-S194, ISSN: 1058-4838
Hardwick RJ, Vegvari C, Collyer B, et al., 2021, Spatial scales in human movement between reservoirs of infection, JOURNAL OF THEORETICAL BIOLOGY, Vol: 524, ISSN: 0022-5193
Collyer BS, Anderson RM, 2021, Probability distributions of helminth parasite burdens within the human host population following repeated rounds of mass drug administration and their impact on the transmission breakpoint, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 18, ISSN: 1742-5689
Vegvari C, Giardina F, Bajaj S, et al., 2021, Deworming women of reproductive age during adolescence and pregnancy: what is the impact on morbidity from soil-transmitted helminths infection?, PARASITES & VECTORS, Vol: 14, ISSN: 1756-3305
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.
Ajjampur SSR, Kaliappan SP, Halliday KE, et al., 2021, Epidemiology of soil transmitted helminths and risk analysis of hookworm infections in the community: Results from the DeWorm3 Trial in southern India, PLOS NEGLECTED TROPICAL DISEASES, Vol: 15, ISSN: 1935-2735
Kura K, Ayabina D, Toor J, et al., 2021, Disruptions to schistosomiasis programmes due to COVID-19: an analysis of potential impact and mitigation strategies., Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol: 115, Pages: 236-244, ISSN: 0035-9203
BACKGROUND: The 2030 goal for schistosomiasis is elimination as a public health problem (EPHP), with mass drug administration (MDA) of praziquantel to school-age children (SAC) as a central pillar of the strategy. However, due to coronavirus disease 2019, many mass treatment campaigns for schistosomiasis have been halted, with uncertain implications for the programmes. METHODS: We use mathematical modelling to explore how postponement of MDA and various mitigation strategies affect achievement of the EPHP goal for Schistosoma mansoni and S. haematobium. RESULTS: For both S. mansoni and S. haematobium in moderate- and some high-prevalence settings, the disruption may delay the goal by up to 2 y. In some high-prevalence settings, EPHP is not achievable with current strategies and so the disruption will not impact this. Here, increasing SAC coverage and treating adults can achieve the goal. The impact of MDA disruption and the appropriate mitigation strategy varies according to the baseline prevalence prior to treatment, the burden of infection in adults and the stage of the programme. CONCLUSIONS: Schistosomiasis MDA programmes in medium- and high-prevalence areas should restart as soon as is feasible and mitigation strategies may be required in some settings.
Malizia V, Giardina F, Vegvari C, et al., 2021, Modelling the impact of COVID-19-related control programme interruptions on progress towards the WHO 2030 target for soil-transmitted helminths, Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol: 115, Pages: 253-260, ISSN: 0035-9203
BACKGROUND: On 1 April 2020, the WHO recommended an interruption of all activities for the control of neglected tropical diseases, including soil-transmitted helminths (STH), in response to the COVID-19 pandemic. This paper investigates the impact of this disruption on the progress towards the WHO 2030 target for STH. METHODS: We used two stochastic individual-based models to simulate the impact of missing one or more preventive chemotherapy (PC) rounds in different endemicity settings. We also investigated the extent to which this impact can be lessened by mitigation strategies, such as semiannual or community-wide PC. RESULTS: Both models show that without a mitigation strategy, control programmes will catch up by 2030, assuming that coverage is maintained. The catch-up time can be up to 4.5 y after the start of the interruption. Mitigation strategies may reduce this time by up to 2 y and increase the probability of achieving the 2030 target. CONCLUSIONS: Although a PC interruption will only temporarily impact the progress towards the WHO 2030 target, programmes are encouraged to restart as soon as possible to minimise the impact on morbidity. The implementation of suitable mitigation strategies can turn the interruption into an opportunity to accelerate progress towards reaching the target.
Hardwick RJ, Werkman M, Truscott JE, et al., 2021, Stochastic challenges to interrupting helminth transmission, EPIDEMICS, Vol: 34, ISSN: 1755-4365
Vikentjeva M, Geller J, Remm J, et al., 2021, Forecasting the effectiveness of the DeWorm3 trial in interrupting the transmission of soil-transmitted helminths in three study sites in Benin, India and Malawi, Parasites and Vectors, Vol: 14, ISSN: 1756-3305
BackgroundThe DeWorm3 project is an ongoing cluster-randomised trial assessing the feasibility of interrupting the transmission of soil-transmitted helminths (STH) through mass drug administration (MDA) using study sites in India, Malawi and Benin. In this article, we describe an approach which uses a combination of statistical and mathematical methods to forecast the outcome of the trial with respect to its stated goal of reducing the prevalence of infection to below 2%.MethodsOur approach is first to define the local patterns of transmission within each study site, which is achieved by statistical inference of key epidemiological parameters using the baseline epidemiological measures of age-related prevalence and intensity of STH infection which have been collected by the DeWorm3 trials team. We use these inferred parameters to calibrate an individual-based stochastic simulation of the trial at the cluster and study site level, which is subsequently run to forecast the future prevalence of STH infections. The simulator takes into account both the uncertainties in parameter estimation and the variability inherent in epidemiological and demographic processes in the simulator. We interpret the forecast results from our simulation with reference to the stated goal of the DeWorm3 trial, to achieve a target of ≤2%prevalence at a point 24 months post-cessation of MDA.ResultsSimulated output predicts that the two arms will be distinguishable from each other in all three country sites at the study end point. In India and Malawi, measured prevalence in the intervention arm is below the threshold with a high probability (90% and 95%, respectively), but in Benin the heterogeneity between clusters prevents the arm prevalence from being reduced below the threshold value. At the level of individual study arms within each site, heterogeneity among clusters leads to a very low probability of achieving complete elimination in an intervention arm, yielding a post-study scenario w
Hardwick RJ, Truscott JE, Oswald WE, et al., 2021, Individual adherence to mass drug administration in neglected tropical disease control: A probability model conditional on past behaviour, PLOS NEGLECTED TROPICAL DISEASES, Vol: 15, ISSN: 1935-2735
Anderson RM, Vegvari C, Truscott J, et al., 2020, Challenges in creating herd immunity to SARS-CoV-2 infection by mass vaccination, The Lancet, Vol: 396, Pages: 1614-1616, ISSN: 0140-6736
Kura K, Hardwick RJ, Truscott JE, et al., 2020, The impact of mass drug administration on Schistosoma haematobium infection: what is required to achieve morbidity control and elimination?, Parasites and Vectors, Vol: 13, Pages: 1-10, ISSN: 1756-3305
BACKGROUND: Schistosomiasis remains an endemic parasitic disease causing much morbidity and, in some cases, mortality. The World Health Organization (WHO) has outlined strategies and goals to combat the burden of disease caused by schistosomiasis. The first goal is morbidity control, which is defined by achieving less than 5% prevalence of heavy intensity infection in school-aged children (SAC). The second goal is elimination as a public health problem (EPHP), achieved when the prevalence of heavy intensity infection in SAC is reduced to less than 1%. Mass drug administration (MDA) of praziquantel is the main strategy for control. However, there is limited availability of praziquantel, particularly in Africa where there is high prevalence of infection. It is therefore important to explore whether the WHO goals can be achieved using the current guidelines for treatment based on targeting SAC and, in some cases, adults. Previous modelling work has largely focused on Schistosoma mansoni, which in advance cases can cause liver and spleen enlargement. There has been much less modelling of the transmission of Schistosoma haematobium, which in severe cases can cause kidney damage and bladder cancer. This lack of modelling has largely been driven by limited data availability and challenges in interpreting these data. RESULTS: In this paper, using an individual-based stochastic model and age-intensity profiles of S. haematobium from two different communities, we calculate the probability of achieving the morbidity and EPHP goals within 15 years of treatment under the current WHO treatment guidelines. We find that targeting SAC only can achieve the morbidity goal for all transmission settings, regardless of the burden of infection in adults. The EPHP goal can be achieved in low transmission settings, but in some moderate to high settings community-wide treatment is needed. CONCLUSIONS: We show that the key determinants of achieving the WHO goals are the precise form of the ag
Easton A, Gao S, Lawton SP, et al., 2020, Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans, eLife, Vol: 9, ISSN: 2050-084X
Human ascariasis is a major neglected tropical disease caused by the nematode Ascaris lumbricoides. We report a 296 megabase (Mb) reference-quality genome comprised of 17,902 protein-coding genes derived from a single, representative Ascaris worm. An additional 68 worms were collected from 60 human hosts in Kenyan villages where pig husbandry is rare. Notably, the majority of these worms (63/68) possessed mitochondrial genomes that clustered closer to the pig parasite Ascaris suum than to A. lumbricoides. Comparative phylogenomic analyses identified over 11 million nuclear-encoded SNPs but just two distinct genetic types that had recombined across the genomes analyzed. The nuclear genomes had extensive heterozygosity, and all samples existed as genetic mosaics with either A. suum-like or A. lumbricoides-like inheritance patterns supporting a highly interbred Ascaris species genetic complex. As no barriers appear to exist for anthroponotic transmission of these 'hybrid' worms, a one-health approach to control the spread of human ascariasis will be necessary.
Lochen A, Croucher N, Anderson R, 2020, Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency, Scientific Reports, Vol: 10, ISSN: 2045-2322
Streptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling all the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.
Oswald WE, Kepha S, Halliday KE, et al., 2020, Patterns of individual non-treatment during multiple rounds of mass drug administration for control of soil-transmitted helminths in the TUMIKIA trial, Kenya: a secondary longitudinal analysis, LANCET GLOBAL HEALTH, Vol: 8, Pages: E1418-E1426, ISSN: 2214-109X
Celma CC, Beard S, Douglas A, et al., 2020, Retrospective analysis on confirmation rates for referred positive rotavirus samples in England, 2016 to 2017: implications for diagnosis and surveillance, Eurosurveillance, Vol: 25, Pages: 1-8, ISSN: 1025-496X
BackgroundRapid diagnostic tests are commonly used by hospital laboratories in England to detect rotavirus (RV), and results are used to inform clinical management and support national surveillance of the infant rotavirus immunisation programme since 2013. In 2017, the Public Health England (PHE) national reference laboratory for enteric viruses observed that the presence of RV could not be confirmed by PCR in a proportion of RV-positive samples referred for confirmatory detection.AimWe aimed to compare the positivity rate of detection methods used by hospital laboratories with the PHE confirmatory test rate.MethodsRotavirus specimens testing positive at local hospital laboratories were re-tested at the PHE national reference laboratory using a PCR test. Confirmatory results were compared to original results from the PHE laboratory information management system.ResultsHospital laboratories screened 70.1% (2,608/3,721) of RV samples using immunochromatographic assay (IC) or rapid tests, 15.5% (578/3,721) using enzyme immunoassays (EIA) and 14.4% (535/3,721) using PCR. Overall, 1,011/3,721 (27.2%) locally RV-positive samples referred to PHE in 2016 and 2017 failed RV detection using the PHE reference laboratory PCR test. Confirmation rates were 66.9% (1,746/2,608) for the IC tests, 87.4% (505/578) for the EIA and 86.4% (465/535) for the PCR assays. Seasonal confirmation rate discrepancies were also evident for IC tests.ConclusionsThis report highlights high false positive rates with the most commonly used RV screening tests and emphasises the importance of implementing verified confirmatory tests for RV detections. This has implications for clinical diagnosis and national surveillance.
Collyer BS, Irvine MA, Hollingsworth TD, et al., 2020, Defining a prevalence level to describe the elimination of Lymphatic Filariasis (LF) transmission and designing monitoring & evaluating (M&E) programmes post the cessation of mass drug administration (MDA), PLoS Neglected Tropical Diseases, Vol: 14, Pages: 1-21, ISSN: 1935-2727
The global decline in prevalence of lymphatic filariasis has been one of the major successes of the WHO’s NTD programme. The recommended strategy of intensive, community-wide mass drug administration, aims to break localised transmission by either reducing the prevalence of microfilaria positive infections to below 1%, or antigen positive infections to below 2%. After the threshold is reached, and mass drug administration is stopped, geographically defined evaluation units must pass Transmission Assessment Surveys to demonstrate that transmission has been interrupted. In this study, we use an empirically parameterised stochastic transmission model to investigate the appropriateness of 1% microfilaria-positive prevalence as a stopping threshold, and statistically evaluate how well various monitoring prevalence-thresholds predict elimination or disease resurgence in the future by calculating their predictive value. Our results support the 1% filaremia prevalence target as appropriate stopping criteria. However, because at low prevalence-levels random events dominate the transmission dynamics, we find single prevalence measurements have poor predictive power for predicting resurgence, which suggests alternative criteria for restarting MDA may be beneficial.
Thomas DX, Bajaj S, McRae-McKee K, et al., 2020, Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer's disease neuropathology, Scientific Reports, Vol: 10, ISSN: 2045-2322
Alzheimer's disease patients typically present with multiple co-morbid neuropathologies at autopsy, but the impact of these pathologies on cognitive impairment during life is poorly understood. In this study, we developed cognitive trajectories for patients with common co-pathologies in the presence and absence of Alzheimer's disease neuropathology. Cognitive trajectories were modelled in a Bayesian hierarchical regression framework to estimate the effects of each neuropathology on cognitive decline as assessed by the mini-mental state examination and the clinical dementia rating scale sum of boxes scores. We show that both TDP-43 proteinopathy and cerebral amyloid angiopathy associate with cognitive impairment of similar magnitude to that associated with Alzheimer's disease neuropathology. Within our study population, 63% of individuals given the 'gold-standard' neuropathological diagnosis of Alzheimer's disease in fact possessed either TDP-43 proteinopathy or cerebral amyloid angiopathy of sufficient severity to independently explain the majority of their cognitive impairment. This suggests that many individuals diagnosed with Alzheimer's disease may actually suffer from a mixed dementia, and therapeutics targeting only Alzheimer's disease-related processes may have severely limited efficacy in these co-morbid populations.
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