Publications
131 results found
Freitas LT, Khan MA, Uddin A, et al., 2024, The lymphatic filariasis treatment study landscape: a systematic review of study characteristics and the case for an individual participant data platform, PLoS Neglected Tropical Diseases, Vol: 18, ISSN: 1935-2727
BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000, more than 9 billion treatments of antifilarial medicines have been distributed through mass drug administration (MDA) programmes in 72 endemic countries and 17 countries have reached EPHP. Yet in 2021, nearly 900 million people still required MDA with combinations of albendazole, diethylcarbamazine and/or ivermectin. Despite the reliance on these drugs, there remain gaps in understanding of variation in responses to treatment. As demonstrated for other infectious diseases, some urgent questions could be addressed by conducting individual participant data (IPD) meta-analyses. Here, we present the results of a systematic literature review to estimate the abundance of IPD on pre- and post-intervention indicators of infection and/or morbidity and assess the feasibility of building a global data repository. METHODOLOGY: We searched literature published between 1st January 2000 and 5th May 2023 in 15 databases to identify prospective studies assessing LF treatment and/or morbidity management and disease prevention (MMDP) approaches. We considered only studies where individual participants were diagnosed with LF infection or disease and were followed up on at least one occasion after receiving an intervention/treatment. PRINCIPAL FINDINGS: We identified 138 eligible studies from 23 countries, having followed up an estimated 29,842 participants after intervention. We estimate 14,800 (49.6%) IPD on pre- and post-intervention infection indicators including microfilaraemia, circulating filarial antigen and/or ultrasound indicators measured before and after intervention using 8 drugs administered in various combinations. We identified 33 studies on MMDP, estimating 6,102 (20.4%) IPD on pre- and post-intervention clinical morbidity indicators only. A further 8,940 IPD cover a mixture of infection and
Savagar B, Jones BA, Arnold M, et al., 2023, Modelling flock heterogeneity in the transmission of peste des petits ruminants virus and its impact on the effectiveness of vaccination for eradication., Epidemics, Vol: 45
Peste des petits ruminants (PPR) is an acute infectious disease of small ruminants targeted for global eradication by 2030. The Global Strategy for Control and Eradication (GSCE) recommends mass vaccination targeting 70% coverage of small ruminant populations in PPR-endemic regions. These small ruminant populations are diverse with heterogeneous mixing patterns that may influence PPR virus (PPRV) transmission dynamics. This paper evaluates the impact of heterogeneous mixing on (i) PPRV transmission and (ii) the likelihood of different vaccination strategies achieving PPRV elimination, including the GSCE recommended strategy. We develop models simulating heterogeneous transmission between hosts, including a metapopulation model of PPRV transmission between villages in lowland Ethiopia fitted to serological data. Our results demonstrate that although heterogeneous mixing of small ruminant populations increases the instability of PPRV transmission-increasing the chance of fadeout in the absence of intervention-a vaccination coverage of 70% may be insufficient to achieve elimination if high-risk populations are not targeted. Transmission may persist despite very high vaccination coverage (>90% small ruminants) if vaccination is biased towards more accessible but lower-risk populations such as sedentary small ruminant flocks. These results highlight the importance of characterizing small ruminant mobility patterns and identifying high-risk populations for vaccination and support a move towards targeted, risk-based vaccination programmes in the next phase of the PPRV eradication programme. Our modelling approach also illustrates a general framework for incorporating heterogeneous mixing patterns into models of directly transmitted infectious diseases where detailed contact data are limited. This study improves understanding of PPRV transmission and elimination in heterogeneous small ruminant populations and should be used to inform and optimize the design of PPRV vacci
Walker M, Lambert S, Neves MI, et al., 2023, Modeling the effectiveness of One Health interventions against the zoonotic hookworm Ancylostoma ceylanicum, Frontiers of Medicine, Vol: 10, ISSN: 1673-7342
Hookworm disease is a major global public health concern, annually affecting 500-700 million of the world's poorest people. The World Health Organization is targeting the elimination of hookworm as a public health problem by 2030 using a strategy of mass drug administration (MDA) to at-risk human populations. However, in Southeast Asia and the Pacific the zoonotic hookworm species, Ancylostoma ceylanicum, is endemic in dogs and commonly infects people. This presents a potential impediment to the effectiveness of MDA that targets only humans. Here, we develop a novel multi-host (dog and human) transmission model of A. ceylanicum and compare the effectiveness of human-only and "One Health" (human plus dog) MDA strategies under a range of eco-epidemiological assumptions. We show that One Health interventions-targeting both dogs and humans-could suppress prevalence in humans to ≤ 1% by the end of 2030, even with only modest coverage (25-50%) of the animal reservoir. With increasing coverage, One Health interventions may even interrupt transmission. We discuss key unresolved questions on the eco-epidemiology of A. ceylanicum, the challenges of delivering MDA to animal reservoirs, and the growing importance of One Health interventions to human public health.
Diaz AVV, Walker M, Webster JPP, 2023, Reaching the World Health Organization elimination targets for schistosomiasis: the importance of a One Health perspective, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 378, ISSN: 0962-8436
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Kura K, Milton P, Hamley JID, et al., 2023, Can mass drug administration of moxidectin accelerate onchocerciasis elimination in Africa?, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 378, Pages: 1-11, ISSN: 0962-8436
Epidemiological and modelling studies suggest that elimination of Onchocerca volvulus transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of O. volvulus microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA.
Calvo-Urbano B, Léger E, Gabain I, et al., 2023, Sensitivity and specificity of human point-of-care circulating cathodic antigen (POC-CCA) test in African livestock for rapid diagnosis of schistosomiasis: A Bayesian latent class analysis, PLoS Neglected Tropical Diseases, Vol: 17, ISSN: 1935-2727
Schistosomiasis is a major neglected tropical disease (NTD) affecting both humans and animals. The morbidity and mortality inflicted upon livestock in the Afrotropical region has been largely overlooked, in part due to a lack of validated sensitive and specific tests, which do not require specialist training or equipment to deliver and interpret. As stressed within the recent WHO NTD 2021-2030 Roadmap and Revised Guideline for schistosomiasis, inexpensive, non-invasive, and sensitive diagnostic tests for livestock-use would also facilitate both prevalence mapping and appropriate intervention programmes. The aim of this study was to assess the sensitivity and specificity of the currently available point-of-care circulating cathodic antigen test (POC-CCA), designed for Schistosoma mansoni detection in humans, for the detection of intestinal livestock schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. POC-CCA, together with the circulating anodic antigen (CAA) test, miracidial hatching technique (MHT) and organ and mesentery inspection (for animals from abattoirs only), were applied to samples collected from 195 animals (56 cattle and 139 small ruminants (goats and sheep) from abattoirs and living populations) from Senegal. POC-CCA sensitivity was greater in the S. curassoni-dominated Barkedji livestock, both for cattle (median 81%; 95% credible interval (CrI): 55%-98%) and small ruminants (49%; CrI: 29%-87%), than in S. bovis-dominated Richard Toll ruminants (cattle: 62%; CrI: 41%-84%; small ruminants: 12%, CrI: 1%-37%). Overall, sensitivity was greater in cattle than in small ruminants. Small ruminants POC-CCA specificity was similar in both locations (91%; CrI: 77%-99%), whilst cattle POC-CCA specificity could not be assessed owing to the low number of uninfected cattle surveyed. Our results indicate that, whilst the current POC-CCA does represent a potential diagnostic tool for cattle and possibly for predominantly S. curassoni-infected livestoc
Smith GC, Kao RR, Walker M, 2023, Infectious disease modelling to inform policy., Rev Sci Tech, Vol: 42, Pages: 173-179, ISSN: 0253-1933
With modelling becoming increasingly important in helping to inform decisions about animal diseases, it is essential that the process be optimised to gain the maximum benefit for the decision-maker. Here, the authors set out ten steps that can improve this process for all concerned. Four steps describe initialisation to ensure that the question, answer and timescale are defined; two steps describe the modelling process and quality assurance; and four steps describe the reporting stage. The authors believe that this greater emphasis at the beginning and end of a modelling project will increase the relevance of the work and understanding of the results, and thus contribute towards better decision-making.
Holt HR, Walker M, Beauvais W, et al., 2023, Modelling the control of bovine brucellosis in India., Journal of the Royal Society Interface, Vol: 20, Pages: 1-11, ISSN: 1742-5662
Brucellosis imposes substantial impacts on livestock production and public health worldwide. A stochastic, age-structured model incorporating herd demographics was developed describing within- and between-herd transmission of Brucella abortus in dairy cattle herds. The model was fitted to data from a cross-sectional study conducted in Punjab State of India and used to evaluate the effectiveness of control strategies under consideration. Based on model results, stakeholder acceptance and constraints regarding vaccine supply, vaccination of replacement calves in large farms should be prioritized. Test and removal applied at early stages of the control programme where seroprevalence is high would not constitute an effective or acceptable use of resources because significant numbers of animals would be 'removed' (culled or not used for breeding) based on false positive results. To achieve sustained reductions in brucellosis, policymakers must commit to maintaining vaccination in the long term, which may eventually reduce frequency of infection in the livestock reservoir to a low enough level for elimination to be a realistic objective. This work provides key strategic insights into the control of brucellosis in India, which has the largest cattle population globally, and a general modelling framework for evaluating control strategies in endemic settings.
Milne GC, Webster JP, Walker M, 2023, Is the incidence of congenital toxoplasmosis declining?, Trends in Parasitology, Vol: 39, Pages: 26-37, ISSN: 0169-4758
Prenatal infection with the protozoan parasite Toxoplasma gondii can cause congenital toxoplasmosis (CT), an often fatal or lifelong-disabling condition. Several studies of human populations have reported temporal decreases in seroprevalence, suggesting declining CT incidence. However, the consistency of this trend among diverse populations remains unclear, as does its implication for prenatal screening programmes, the major intervention against CT. Using temporally resolved data on the seroprevalence of T. gondii in various countries, we discuss how the parasite's changing epidemiology may affect trends in CT incidence in varying and counterintuitive ways. We argue that parasite stage-specific serology could be helpful for understanding underlying causes of secular changes in seroprevalence. Furthermore, we highlight the importance of updating cost-effectiveness estimates of screening programmes, accounting for neuropsychiatric sequelae.
Whittaker C, Chesnais CB, Pion SDS, et al., 2022, Factors associated with variation in single-dose albendazole pharmacokinetics: A systematic review and modelling analysis, PLOS NEGLECTED TROPICAL DISEASES, Vol: 16, ISSN: 1935-2735
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Pennance T, Neves MI, Webster BL, et al., 2022, Potential drivers for schistosomiasis persistence: Population genetic analyses from a cluster-randomized urogenital schistosomiasis elimination trial across the Zanzibar islands, PLOS NEGLECTED TROPICAL DISEASES, Vol: 16, ISSN: 1935-2735
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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.
Whittaker C, Chesnais CB, Pion SDS, et al., 2022, Factors associated with variation in single-dose albendazole pharmacokinetics: A systematic review and modelling analysis
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown the drug to be characterised by significant inter-individual pharmacokinetic variation. This variation is thought to have important consequences for treatment success, but current understanding of the factors associated with this variation remains incomplete.</jats:p></jats:sec><jats:sec><jats:title>Methodology/Principal Findings</jats:title><jats:p>We carried out a systematic review to identify references containing temporally disaggregated data on the blood concentration of albendazole and/or (its pharmacologically-active metabolite) albendazole sulfoxide following a single oral dose. These data were then integrated into a mathematical modelling framework to infer key pharmacokinetic parameters and relate them to characteristics of the populations being treated. These characteristics included age, weight, sex, dosage, infection status, and whether patients had received a fatty meal prior to treatment or other drugs alongside albendazole. Our results highlight a number of factors systematically associated with albendazole pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. These factors impact different aspects of the drug’s pharmacokinetic profile. Whilst age is significantly associated with albendazole sulfoxide half-life, receipt of a fatty meal prior to treatment was associated with increased albendazole bioavailability (and by extension, peak blood concentration and total drug exposure following the dose). Parasitic infection (particularly echinococcosis and neurocysticercosis) was associated with altered pharmacokinetic parameters, with infected populations displaying distinct characteris
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 Research, 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.
Guest C, Dewhirst SY, Lindsay SW, et al., 2022, Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study, Journal of Travel Medicine, Vol: 29, Pages: 1-10, ISSN: 1195-1982
BACKGROUND: A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry. METHODS: Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening. RESULTS: About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95-100) to 100% and specificity from 99% (95% CI 97-100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76-87) to 94% (95% CI 89-98) and specificity ranging from 76% (95% CI 70-82) to 92% (95% CI 88-96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only. CONCLUSIONS: People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people.Trial Registration NCT04509713 (clinicaltrials.gov).
Dixon M, Winskill P, Harrison W, et al., 2022, Global force-of-infection trends for human <i>taenia solium</i> taeniasis/cysticercosis, Publisher: Medrxiv
Infection by Taenia solium poses a major burden across endemic countries. The World Health Organization (WHO) 2021–2030 Neglected Tropical Diseases roadmap has proposed that 30% of endemic countries achieve intensified T. solium control in hyperendemic areas by 2030. Understanding geographical variation in age-prevalence profiles and force-of-infection (FoI) estimates will inform intervention designs across settings. Human taeniasis (HTT) and human cysticercosis (HCC) age-prevalence data from 16 studies in Latin America, Africa and Asia were extracted through a systematic review. Catalytic models, incorporating diagnostic performance uncertainty, were fitted to the data using Bayesian methods, to estimate rates of antibody (Ab)-seroconversion, infection acquisition and Ab-seroreversion or infection loss. HCC FoI and Ab-seroreversion rates were also estimated across 23 departments in Colombia from 28,100 individuals. Across settings, there was extensive variation in all-ages seroprevalence. Evidence for Ab- seroreversion or infection loss was found in most settings for both HTT and HCC and for HCC Ab- seroreversion in Colombia. The average duration until humans became Ab-seropositive/infected decreased as all-age (sero)prevalence increased. There was no clear relationship between the average duration humans remain Ab-seropositive and all-age seroprevalence. Marked geographical heterogeneity in T. solium transmission rates indicate the need for setting- specific intervention strategies to achieve the WHO goals.
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.
Díaz AV, Walker M, Webster JP, 2021, Surveillance and control of SARS-CoV-2 in mustelids: An evolutionary perspective., Evolutionary Applications: evolutionary approaches to environmental, biomedical and socio-economic issues, Vol: 14, Pages: 2715-2725, ISSN: 1752-4563
The relevance of mustelids in SARS-CoV-2 transmission has become increasingly evident. Alongside experimental demonstration of airborne transmission among ferrets, the major animal model for human respiratory diseases, transmission of SARS-CoV-2 within- and/or between-commercial mink farms has occurred and continues to occur. The number of mink reared for the luxury fur trade is approximately 60.5 million, across 36 mustelid-farming countries. By July 2021, SARS-CoV-2 outbreaks have been reported in 12 of these countries, at 412 European and 20 North American mink farms. Reverse zoonotic transmission events (from humans to mink) have introduced the virus to farms with subsequent extensive mink-to-mink transmission as well as further zoonotic (mink-to-human) transmission events generating cases among both farm workers and the broader community. Overcrowded housing conditions inherent within intensive mink farms, often combined with poor sanitation and welfare, both guarantee spread of SARS-CoV-2 and facilitate opportunities for viral variants, thereby effectively representing biotic hubs for viral transmission and evolution of virulence. Adequate preventative, surveillance and control measures within the mink industry are imperative both for the control of the current global pandemic and to mitigate against future outbreaks.
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
Walker M, Cools P, Albonico M, et al., 2021, Individual responses to a single oral dose of albendazole indicate reduced efficacy against soil-transmitted helminths in an area with high drug pressure, PLoS Neglected Tropical Diseases, Vol: 15, Pages: 1-16, ISSN: 1935-2727
BackgroundAlbendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment.Methodology/Principal findingsWe re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People’s Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites.Conclusions/SignificanceWe found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment
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.
Fall CB, Lambert S, Leger E, et al., 2021, Hybridized zoonotic schistosoma infections result in hybridized morbidity profiles: a clinical morbidity study amongst co-infected human populations of Senegal, Microorganisms, Vol: 9, Pages: 1-18, ISSN: 2076-2607
Hybridization of infectious agents is a major emerging public and veterinary health concern at the interface of evolution, epidemiology, and control. Whilst evidence of the extent of hybridization amongst parasites is increasing, their impact on morbidity remains largely unknown. This may be predicted to be particularly pertinent where parasites of animals with contrasting pathogenicity viably hybridize with human parasites. Recent research has revealed that viable zoonotic hybrids between human urogenital Schistosoma haematobium with intestinal Schistosoma species of livestock, notably Schistosoma bovis, can be highly prevalent across Africa and beyond. Examining human populations in Senegal, we found increased hepatic but decreased urogenital morbidity, and reduced improvement following treatment with praziquantel, in those infected with zoonotic hybrids compared to non-hybrids. Our results have implications for effective monitoring and evaluation of control programmes, and demonstrate for the first time the potential impact of parasite hybridizations on host morbidity.
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.
Coffeng LE, Levecke B, Hattendorf J, et al., 2021, Survey design to monitor drug efficacy for the control of soil-transmitted helminthiasis and schistosomiasis., Clinical Infectious Diseases, Vol: 72, Pages: S195-S202, ISSN: 1058-4838
BACKGROUND: Control of soil-transmitted helminthiasis and schistosomiasis relies heavily on regular preventive chemotherapy. Monitoring drug efficacy is crucial to provide early warning of treatment failures. The World Health Organization (WHO) recommends a survey design in which only egg-positive individuals are retested after treatment. Although this practice makes more efficient use of resources, it may lead to biased drug efficacy estimates. METHODS: We performed a simulation study to assess the potential for bias when evaluating drug efficacy using the World Health Organization-recommended survey design, and to identify alternative designs for evaluating drug efficacy that are less affected by bias. These designs were also based on selection of egg-positive individuals, but involve retesting them a second time at baseline and up to 2 times at follow-up. The utility of the different designs was compared fairly by constraining them to the same budget. RESULTS: The standard procedure of selecting egg-positive individuals can introduce a substantial positive bias in drug efficacy due to regression toward the mean, particularly when infection levels or drug efficacy are low. This bias was completely eliminated by using a second baseline sample, conditionally on the first sample being excluded from analysis. Precision of estimates can be improved by increasing the number of thick smears and/or samples per person at follow-up, despite fewer individuals being tested within the same budget. CONCLUSIONS: We present optimized survey designs to monitor drug efficacy in field settings, which are highly relevant for sustained control of soil-transmitted helminths and schistosomiasis, as well as onchocerciasis and lymphatic filariasis.
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.
Neves MI, Gower CM, Webster JP, et al., 2021, Revisiting density-dependent fecundity in schistosomes using sibship reconstruction., PLoS Neglected Tropical Diseases, Vol: 15, Pages: 1-16, ISSN: 1935-2727
The stability of parasite populations is regulated by density-dependent processes occurring at different stages of their life cycle. In dioecious helminth infections, density-dependent fecundity is one such regulatory process that describes the reduction in egg production by female worms in high worm burden within-host environments. In human schistosomiasis, the operation of density-dependent fecundity is equivocal and investigation is hampered by the inaccessibility of adult worms that are located intravascularly. Current understanding is almost exclusively limited to data collected from two human autopsy studies conducted over 40 years ago, with subsequent analyses having reached conflicting conclusions. Whether egg production is regulated in a density-dependent manner is key to predicting the effectiveness of interventions targeting the elimination of schistosomiasis and to the interpretation of parasitological data collected during monitoring and evaluation activities. Here, we revisit density-dependent fecundity in the two most globally important human Schistosoma spp. using a statistical modelling approach that combines molecular inference on the number of parents/adult worms in individual human hosts with parasitological egg count data from mainland Tanzania and Zanzibar. We find a non-proportional relationship between S. haematobium egg counts and inferred numbers of female worms, providing the first clear evidence of density-dependent fecundity in this schistosome species. We do not find robust evidence for density-dependent fecundity in S. mansoni because of high sensitivity to some modelling assumptions and the lower statistical power of the available data. We discuss the strengths and limitations of our model-based analytical approach and its potential for improving our understanding of density dependence in schistosomiasis and other human helminthiases earmarked for elimination.
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.
Hamley JID, Blok DJ, Walker M, et al., 2021, What does the COVID-19 pandemic mean for the next decade of onchocerciasis control and elimination?, Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol: 115, Pages: 269-280, ISSN: 0035-9203
BACKGROUND: Mass drug administration (MDA) of ivermectin for onchocerciasis has been disrupted by the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modelling can help predict how missed/delayed MDA will affect short-term epidemiological trends and elimination prospects by 2030. METHODS: Two onchocerciasis transmission models (EPIONCHO-IBM and ONCHOSIM) are used to simulate microfilarial prevalence trends, elimination probabilities and age profiles of Onchocerca volvulus microfilarial prevalence and intensity for different treatment histories and transmission settings, assuming no interruption, a 1-y (2020) interruption or a 2-y (2020-2021) interruption. Biannual MDA or increased coverage upon MDA resumption are investigated as remedial strategies. RESULTS: Programmes with shorter MDA histories and settings with high pre-intervention endemicity will be the most affected. Biannual MDA is more effective than increasing coverage for mitigating COVID-19's impact on MDA. Programmes that had already switched to biannual MDA should be minimally affected. In high-transmission settings with short treatment history, a 2-y interruption could lead to increased microfilarial load in children (EPIONCHO-IBM) and adults (ONCHOSIM). CONCLUSIONS: Programmes with shorter (annual MDA) treatment histories should be prioritised for remedial biannual MDA. Increases in microfilarial load could have short- and long-term morbidity and mortality repercussions. These results can guide decision-making to mitigate the impact of COVID-19 on onchocerciasis elimination.
Cheke RA, Little KE, Young S, et al., 2021, Taking the strain out of onchocerciasis? A reanalysis of blindness and transmission data does not support the existence of a savannah blinding strain of onchocerciasis in West Africa, ADVANCES IN PARASITOLOGY, VOL 112, Editors: Rollinson, Stothard, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 1-50
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