The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected Africa... more The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. Current control focuses on community-directed treatment with ivermectin (CDTI). In Ghana, persistent transmission has been reported despite long-term control. We present spatial and temporal patterns of onchocerciasis transmission in relation to ivermectin treatment history. Host-seeking and ovipositing blackflies were collected from seven villages in four regions of Ghana with 3-24 years of CDTI at the time of sampling. A total of 16,443 flies was analysed for infection; 5,812 (35.3%) were dissected for parity (26.9% parous). Heads and thoraces of 12,196 flies were dissected for Onchocerca spp. and DNA from 11,122 abdomens was amplified using Onchocerca primers. A total of 463 larvae (0.03 larvae/fly) from 97 (0.6%) infected and 62 (0.4%) infective flies was recorded; 258 abdomens (2.3%) were positive for Onchocerca DNA. Infections (all were O. volvulus) were more likely to...
Despite many current interventions against neglected tropical diseases (NTDs) being highly cost-e... more Despite many current interventions against neglected tropical diseases (NTDs) being highly cost-effective, new strategies are needed to reach the WHO's control and elimination goals. Here we argue for the importance of incorporating economic evaluations of new strategies in decisions regarding resource allocation. Such evaluation should ideally be conducted using dynamic transmission models that capture inherent nonlinearities in transmission and the indirect benefits ('herd effects') of interventions. A systematic review of mathematical models that have been used for economic analysis of interventions against the ten NTDs covered by the London Declaration reveals that only 16 out of 49 studies used dynamic transmission models, highlighting a fundamental--but addressable--gap in the evaluation of interventions against NTDs.
Background. Recently, there has been a shift in onchocerciasis control policy, changing from prev... more Background. Recently, there has been a shift in onchocerciasis control policy, changing from prevention of morbidity toward elimination of infection. Switching from annual to biannual ivermectin distribution may accelerate progress toward the elimination goals. However, the settings where this strategy would be cost effective in Africa have not been described. Methods. An onchocerciasis transmission framework (EpiOncho) was coupled to a disease model in order to explore the impact on disability-adjusted life years averted, program cost, and program duration of biannual ivermectin treatment in different epidemiological and programmatic scenarios in African savannah. Results. While biannual treatment yields only small additional health gains, its benefit is pronounced in the context of the elimination goals, shortening the time frames for and increasing the feasibility of reaching the proposed operational thresholds for stopping treatment. In settings with high precontrol endemicity (and/or poor coverage and compliance), it may not be possible to reach such thresholds even within 50 years of annual ivermectin, requiring adoption of biannual treatment. Our projections highlight the crucial role played by coverage and compliance in achieving the elimination goals. Conclusions. Biannual ivermectin treatment improves the chances of reaching the 2020/2025 elimination goals, potentially generating programmatic cost savings in settings with high precontrol endemicity. However, its benefit and cost are highly sensitive to levels of systematic noncompliance and, in many settings, it will lead to an increase in costs. Furthermore, it may not always be feasible to implement biannual treatment, particularly in hard-to-reach populations. This highlights the continued need for a macrofilaricide.
Human onchocerciasis is a chronic parasitic disease caused by Onchocerca volvulus and transmitted... more Human onchocerciasis is a chronic parasitic disease caused by Onchocerca volvulus and transmitted by Simulium black flies. Clinical manifestations include skin and eye disease, leading to loss of vision and blindness. The interaction between parasite, transmitting fly (vector), and human host highlights the relationship between environmental variables and infection risk. Environmental, cultural, entomological, and parasitological features influencing the heterogeneous geographical distribution of onchocerciasis in the Amazonian onchocerciasis focus of southern Venezuela are described and discussed. Unique features of the region where this focus is located include its ancient geological origin, highly structured and varied landscapes, large extensions of rainforest and mountainous areas crisscrossed by rivers where transmission occurs, seminomadic and rainforest-dwelling characteristics of the at-risk Yanomami population inhabiting the area, and multiplicity of Simulium vectors. Use of a landscape epidemiology approach and application of remote sensing and geographical information system technologies have permitted identification and mapping of environmental variables and landscape elements that collectively provide the niche in which the dynamics of parasite, human, and vector populations take place, both locally and connectedly. A thorough, yet holistic understanding of this host–parasite–vector system in intimate relationship with its special environment is essential for successful onchocerciasis control in the Amazonian focus.
PLoS Neglected Tropical Diseases is an open-access journal publishing peer-reviewed research on t... more PLoS Neglected Tropical Diseases is an open-access journal publishing peer-reviewed research on the world\'s most neglected tropical diseases, such as elephantiasis, river blindness, leprosy, hookworm, schistosomiasis, and African sleeping sickness.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1997
A recently described hyperendemic onchocerciasis area, located in the Unturin Mountains (between ... more A recently described hyperendemic onchocerciasis area, located in the Unturin Mountains (between the Siapa and Orinoco basins) of southernvenezuela was studied using a cocktail of 3 low molecular weight onchocercal recombinant antigens (OvMBWlO, OvMBWl 1, and OvMBW29). The resulting seroepidemiological data were compared with those from a hypoendemic community (Altamira) situated in the northern coastal mountain range. Parasitological (skin biopsy) and serological (enzyme-linked immunosorbent assay, ELISA) methods for the specific diagnosis of Onchocerca volvuZus in these 2 very different endemic areas were, respectively, 88% and 96% sensitive in Untursn, and 57% and 91% sensitive in Altamira. The mean microfilarial load, the mean optical density (OD), and the seropositivity rates all increased significantly with age in both communities.The serological variables (mean OD and prevalence of anti-O. volvulus antibodies) were both significantly higher in Unturin than in Altamira for children and young adults (aged ~25 years), although above this age no differences between communities were detected. Seroprevalence had already reached 50% in the under 15 year-olds examined at Unturin but was just 5% at Altamira for the same age-class.The prevalence of specific antibodies (mainly a marker of exposure to risk of infection) exceeded 85% in the remaining age-categories at the hyperendemic area. This is in agreement with the high community microfilarial load recorded in Unturhn (>20 mE/mg) and the presence of sclerosing keratitis and hanging groin, suggesting that onchocerciasis is a public health problem in this community. The ELISA test used here, based on a cocktail of 3 low molecular weight onchocercal recombinant antigens, appears, therefore, to constitute a practical tool for the description of endemicity levels in remote areas, particularly given the fact that finger-prick blood samples are routinely taken from children in the Upper Orinoco region for surveys of malaria incidence. Such studies could aid in defining the true extent of the Amazon focus (still unknown) and providing priority indicators for the selection of communities where onchocerciasis control programmes should be implemented.
The relation between the number of microÞlariae (mf) ingested by host-seeking vectors of human on... more The relation between the number of microÞlariae (mf) ingested by host-seeking vectors of human onchocerciasis and skin mf load is an important component of the population biology of Onchocerca volvulus, with implications for disease control and evaluation of the risk of transmission recrudescence. The microsimulation model ONCHOSIM has been used to assess such risk in the area of the Onchocerciasis Control Program (OCP) in West Africa, based on a strongly nonlinear relation between vector mf uptake and human mf skin density previously published. However, observed levels of recrudescence have exceeded predictions, warranting a recalibration of the model. To this end, we present the results of a series of ßy-feeding experiments carried out in savanna and forest localities of West Africa. Flies belonging to Simulium damnosum s.s., S. sirbanum, S. soubrense, and S. leonense were fed on mf carriers and dissected to assess the number of ingested mf escaping imprisonment by the peritrophic matrix (the number of exo-peritrophic mf), a predictor of infective larval output. The method of instrumental variables was used to obtain (nearly) unbiased estimates of the parameters of interest, taking into account error in the measurement of skin mf density. This error is often neglected in these types of studies, making it difÞcult to ascertain the degree of density-dependence truly present in the relation between mf uptake and skin load. We conclude that this relation is weakly (yet signiÞcantly) nonlinear in savanna settings but indistinguishable from linearity in forest vectors. Exo-peritrophic mf uptake does not account for most of the density dependence in the transmission dynamics of the parasite as previously thought. The number of exo-mf in forest simuliids is at least Þve times higher than in the savanna vectors. Parasite abundance in human onchocerciasis is regulated by poorly known mechanisms operating mainly on other stages of the lifecycle.
Since 1987 onchocerciasis control has relied on the donation of ivermectin (Mectizan ® , Merck & ... more Since 1987 onchocerciasis control has relied on the donation of ivermectin (Mectizan ® , Merck & Co., Inc.) through the Mectizan Donation Programme. Recently, concern has been raised over the appearance of suboptimal responses to ivermectin in Ghana-highlighting the potential threat of the development of resistance to ivermectin. This report summarises a meeting held in Ghana to set the research agenda for future onchocerciasis control. The aim of this workshop was to define the research priorities for alternative drug and treatment regimes and control strategies to treat populations with existing evidence of suboptimal responsiveness and define research priorities for future control strategies in the event of the development of widespread ivermectin resistance.
To evaluate micro-haematuria, detected by Haemastix reagent strips, for diagnosis of urinary schi... more To evaluate micro-haematuria, detected by Haemastix reagent strips, for diagnosis of urinary schistosomiasis during a 3-year period of school-based control on Zanzibar. A sub-set of school children, from a total of 135,000 who were receiving treatment for urinary schistosomiasis and soil-transmitted helminthiasis, were monitored by parasitological and questionnaire methods for Schistosoma haematobium infections: at treatment baseline in 2004 (n=2002), follow up with re-treatment in 2005 (n=3278) and further follow up with re-treatment in 2006 (n=3993). Standard diagnostic scores for micro-haematuria were calculated against parasitological assessment. Diagnostic scores of Haemastix remained strong throughout the 3-year period. In 2006, scores were: sensitivity (SS)=0.86 (95% CI: 0.86-0.88), specificity (SP)=0.99 (0.98-1.00), positive predictive value (PPV)=0.90 (0.88-0.91), negative predictive value (NPV)=0.98 (0.98-0.99) in boys; and SS=0.84 (0.82-0.86), SP=0.98 (0.98-0.99), PPV=0.77 (0.75-0.79) and NPV=0.99 (0.99-1.00) in girls. By comparison, reported blood in urine and pain upon urination were much lower and not as informative. At a cost of approximately pound sterling 0.20/test, further use of reagent strips for monitoring of urinary schistosomiasis during ongoing control programmes should be advocated as a rapid, cost-effective and informative disease surveillance tool.
As part of a 4-year control programme beginning in 2003 and entitled Piga Vita Kichocho, around 1... more As part of a 4-year control programme beginning in 2003 and entitled Piga Vita Kichocho, around 140,000 school-aged children on Unguja Island, Zanzibar were treated annually with a combination of praziquantel and albendazole. To provide information on the impact of this intervention, a subset of children, originating from 24 sentinel schools, were monitored in 2004, 2005 and 2006 using both parasitological and behavioural questionnaire methods. Overall, prevalence of urinary schistosomiasis fell by 52%, intensity by 55% and gross haematuria by 82%. There was a positive and statistically significant correlation between areas of elevated disease prevalence and areas of predicted high transmission based upon local occurrence of the permissive intermediate snail host. In areas of low transmission, urinary schistosomiasis was greatly reduced, but, by contrast, other intervention strategies are needed to complement and synergise with chemotherapy in high transmission areas. Whereas significant reductions were documented in the prevalence of both Trichuris trichiura and hookworm, prevalence of Ascaris lumbricoides significantly increased over the monitoring period. Through a detailed analysis of named child records, evidence of predisposition to helminth (re)infection and individual bias towards polyparasitism was detected, highlighting the often overlapping distribution of these parasites within the school-aged child.
Bayesian statistical methods are increasingly being used in the analysis of parasitological data.... more Bayesian statistical methods are increasingly being used in the analysis of parasitological data. Here, the basis of differences between the Bayesian method and the classical or frequentist approach to statistical inference is explained. This is illustrated with practical implications ...
BACKGROUND: Since 1991, in Mexico, ivermectin has been administered twice a year to all residents... more BACKGROUND: Since 1991, in Mexico, ivermectin has been administered twice a year to all residents in the onchocerciasis endemic foci which are mainly located in the coffee growing areas. However, the presence of a potentially infected itinerant seasonal labour force which is not treated regularly could jeopardise the attainment of the 85% coverage which is the present target for elimination
Background: Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual)... more Background: Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual) ivermectin round. However, other modelling-based analyses suggest that ivermectin may not have such a cumulative effect. Uncertainty in this (biological) and other (programmatic) assumptions would affect projected outcomes of long-term ivermectin treatment. Methodology/Principal Findings: We modify a deterministic age-and sex-structured onchocerciasis transmission model, parameterised for savannah O. volvulus-Simulium damnosum, to explore the impact of assumptions regarding the effect of ivermectin on worm fertility and the patterns of treatment coverage compliance, and frequency on projections of parasitological outcomes due to long-term, mass ivermectin administration in hyperendemic areas. The projected impact of ivermectin distribution on onchocerciasis and the benefits of switching from annual to biannual distribution are strongly dependent on assumptions regarding the drug's effect on worm fertility and on treatment compliance. If ivermectin does not have a cumulative impact on microfilarial production, elimination of onchocerciasis in hyperendemic areas may not be feasible with annual ivermectin distribution. Conclusions/Significance: There is substantial (biological and programmatic) uncertainty surrounding modelling projections of onchocerciasis elimination. These uncertainties need to be acknowledged for mathematical models to inform control policy reliably. Further research is needed to elucidate the effect of ivermectin on O. volvulus reproductive biology and quantify the patterns of coverage and compliance in treated communities.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jun 21, 2016
Several African countries have adopted a biannual ivermectin distribution strategy in some foci ... more Several African countries have adopted a biannual ivermectin distribution strategy in some foci to control and eliminate onchocerciasis. In 2010, the Ghana Health Service started biannual distribution to combat transmission hotspots and sub-optimal responses to treatment. We assessed the epidemiological impact of the first 3 years of this strategy and quantified responses to ivermectin over two consecutive rounds of treatment in 10 sentinel communities. We evaluated Onchocerca volvulus microfilarial intensity and prevalence in those aged ≥20 years before the first, second and fifth (or sixth) biannual treatment rounds using skin snip data from 956 participants. We used longitudinal regression modelling to estimate rates of microfilarial repopulation of the skin in a cohort of 217 participants who were followed-up over the first two rounds of biannual treatment. Biannual treatment has had a positive impact, with substantial reductions in infection intensity after 4 or 5 rounds in ...
Recognising the burden helminth infections impose on human populations, and particularly the poor... more Recognising the burden helminth infections impose on human populations, and particularly the poor, major intervention programmes have been launched to control onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, and cysticercosis. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research
To develop a Bayesian hierarchical model for human onchocerciasis with which to explore the facto... more To develop a Bayesian hierarchical model for human onchocerciasis with which to explore the factors that influence prevalence of microfilariae in the Amazonian focus of onchocerciasis and predict the probability of any community being at least mesoendemic (>20% prevalence of microfilariae), and thus in need of priority ivermectin treatment. Models were developed with data from 732 individuals aged > or =15 years who lived in 29 Yanomami communities along four rivers of the south Venezuelan Orinoco basin. The models' abilities to predict prevalences of microfilariae in communities were compared. The deviance information criterion, Bayesian P-values, and residual values were used to select the best model with an approximate cross-validation procedure. A three-level model that acknowledged clustering of infection within communities performed best, with host age and sex included at the individual level, a river-dependent altitude effect at the community level, and additional c...
It is well documented that the density of Plasmodium in its vertebrate host modulates the physiol... more It is well documented that the density of Plasmodium in its vertebrate host modulates the physiological response induced; this in turn regulates parasite survival and transmission. It is less clear that parasite density in the mosquito regulates survival and transmission of this important pathogen. Numerous studies have described conversion rates of Plasmodium from one life stage to the next within the mosquito, yet few have considered that these rates might vary with parasite density. Here we establish infections with defined numbers of the rodent malaria parasite Plasmodium berghei to examine how parasite density at each stage of development (gametocytes; ookinetes; oocysts and sporozoites) influences development to the ensuing stage in Anopheles stephensi, and thus the delivery of infectious sporozoites to the vertebrate host. We show that every developmental transition exhibits strong density dependence, with numbers of the ensuing stages saturating at high density. We further show that when fed ookinetes at very low densities, oocyst development is facilitated by increasing ookinete number (i.e., the efficiency of ookinete-oocyst transformation follows a sigmoid relationship). We discuss how observations on this model system generate important hypotheses for the understanding of malaria biology, and how these might guide the rational analysis of interventions against the transmission of the malaria parasites of humans by their diverse vector species. Citation: Sinden RE, Dawes EJ, Alavi Y, Waldock J, Finney O, et al. (2007) Progression of Plasmodium berghei through Anopheles stephensi is density-dependent. PLoS Pathog 3(12): e195.
The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected Africa... more The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. Current control focuses on community-directed treatment with ivermectin (CDTI). In Ghana, persistent transmission has been reported despite long-term control. We present spatial and temporal patterns of onchocerciasis transmission in relation to ivermectin treatment history. Host-seeking and ovipositing blackflies were collected from seven villages in four regions of Ghana with 3-24 years of CDTI at the time of sampling. A total of 16,443 flies was analysed for infection; 5,812 (35.3%) were dissected for parity (26.9% parous). Heads and thoraces of 12,196 flies were dissected for Onchocerca spp. and DNA from 11,122 abdomens was amplified using Onchocerca primers. A total of 463 larvae (0.03 larvae/fly) from 97 (0.6%) infected and 62 (0.4%) infective flies was recorded; 258 abdomens (2.3%) were positive for Onchocerca DNA. Infections (all were O. volvulus) were more likely to...
Despite many current interventions against neglected tropical diseases (NTDs) being highly cost-e... more Despite many current interventions against neglected tropical diseases (NTDs) being highly cost-effective, new strategies are needed to reach the WHO's control and elimination goals. Here we argue for the importance of incorporating economic evaluations of new strategies in decisions regarding resource allocation. Such evaluation should ideally be conducted using dynamic transmission models that capture inherent nonlinearities in transmission and the indirect benefits ('herd effects') of interventions. A systematic review of mathematical models that have been used for economic analysis of interventions against the ten NTDs covered by the London Declaration reveals that only 16 out of 49 studies used dynamic transmission models, highlighting a fundamental--but addressable--gap in the evaluation of interventions against NTDs.
Background. Recently, there has been a shift in onchocerciasis control policy, changing from prev... more Background. Recently, there has been a shift in onchocerciasis control policy, changing from prevention of morbidity toward elimination of infection. Switching from annual to biannual ivermectin distribution may accelerate progress toward the elimination goals. However, the settings where this strategy would be cost effective in Africa have not been described. Methods. An onchocerciasis transmission framework (EpiOncho) was coupled to a disease model in order to explore the impact on disability-adjusted life years averted, program cost, and program duration of biannual ivermectin treatment in different epidemiological and programmatic scenarios in African savannah. Results. While biannual treatment yields only small additional health gains, its benefit is pronounced in the context of the elimination goals, shortening the time frames for and increasing the feasibility of reaching the proposed operational thresholds for stopping treatment. In settings with high precontrol endemicity (and/or poor coverage and compliance), it may not be possible to reach such thresholds even within 50 years of annual ivermectin, requiring adoption of biannual treatment. Our projections highlight the crucial role played by coverage and compliance in achieving the elimination goals. Conclusions. Biannual ivermectin treatment improves the chances of reaching the 2020/2025 elimination goals, potentially generating programmatic cost savings in settings with high precontrol endemicity. However, its benefit and cost are highly sensitive to levels of systematic noncompliance and, in many settings, it will lead to an increase in costs. Furthermore, it may not always be feasible to implement biannual treatment, particularly in hard-to-reach populations. This highlights the continued need for a macrofilaricide.
Human onchocerciasis is a chronic parasitic disease caused by Onchocerca volvulus and transmitted... more Human onchocerciasis is a chronic parasitic disease caused by Onchocerca volvulus and transmitted by Simulium black flies. Clinical manifestations include skin and eye disease, leading to loss of vision and blindness. The interaction between parasite, transmitting fly (vector), and human host highlights the relationship between environmental variables and infection risk. Environmental, cultural, entomological, and parasitological features influencing the heterogeneous geographical distribution of onchocerciasis in the Amazonian onchocerciasis focus of southern Venezuela are described and discussed. Unique features of the region where this focus is located include its ancient geological origin, highly structured and varied landscapes, large extensions of rainforest and mountainous areas crisscrossed by rivers where transmission occurs, seminomadic and rainforest-dwelling characteristics of the at-risk Yanomami population inhabiting the area, and multiplicity of Simulium vectors. Use of a landscape epidemiology approach and application of remote sensing and geographical information system technologies have permitted identification and mapping of environmental variables and landscape elements that collectively provide the niche in which the dynamics of parasite, human, and vector populations take place, both locally and connectedly. A thorough, yet holistic understanding of this host–parasite–vector system in intimate relationship with its special environment is essential for successful onchocerciasis control in the Amazonian focus.
PLoS Neglected Tropical Diseases is an open-access journal publishing peer-reviewed research on t... more PLoS Neglected Tropical Diseases is an open-access journal publishing peer-reviewed research on the world\'s most neglected tropical diseases, such as elephantiasis, river blindness, leprosy, hookworm, schistosomiasis, and African sleeping sickness.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 1997
A recently described hyperendemic onchocerciasis area, located in the Unturin Mountains (between ... more A recently described hyperendemic onchocerciasis area, located in the Unturin Mountains (between the Siapa and Orinoco basins) of southernvenezuela was studied using a cocktail of 3 low molecular weight onchocercal recombinant antigens (OvMBWlO, OvMBWl 1, and OvMBW29). The resulting seroepidemiological data were compared with those from a hypoendemic community (Altamira) situated in the northern coastal mountain range. Parasitological (skin biopsy) and serological (enzyme-linked immunosorbent assay, ELISA) methods for the specific diagnosis of Onchocerca volvuZus in these 2 very different endemic areas were, respectively, 88% and 96% sensitive in Untursn, and 57% and 91% sensitive in Altamira. The mean microfilarial load, the mean optical density (OD), and the seropositivity rates all increased significantly with age in both communities.The serological variables (mean OD and prevalence of anti-O. volvulus antibodies) were both significantly higher in Unturin than in Altamira for children and young adults (aged ~25 years), although above this age no differences between communities were detected. Seroprevalence had already reached 50% in the under 15 year-olds examined at Unturin but was just 5% at Altamira for the same age-class.The prevalence of specific antibodies (mainly a marker of exposure to risk of infection) exceeded 85% in the remaining age-categories at the hyperendemic area. This is in agreement with the high community microfilarial load recorded in Unturhn (>20 mE/mg) and the presence of sclerosing keratitis and hanging groin, suggesting that onchocerciasis is a public health problem in this community. The ELISA test used here, based on a cocktail of 3 low molecular weight onchocercal recombinant antigens, appears, therefore, to constitute a practical tool for the description of endemicity levels in remote areas, particularly given the fact that finger-prick blood samples are routinely taken from children in the Upper Orinoco region for surveys of malaria incidence. Such studies could aid in defining the true extent of the Amazon focus (still unknown) and providing priority indicators for the selection of communities where onchocerciasis control programmes should be implemented.
The relation between the number of microÞlariae (mf) ingested by host-seeking vectors of human on... more The relation between the number of microÞlariae (mf) ingested by host-seeking vectors of human onchocerciasis and skin mf load is an important component of the population biology of Onchocerca volvulus, with implications for disease control and evaluation of the risk of transmission recrudescence. The microsimulation model ONCHOSIM has been used to assess such risk in the area of the Onchocerciasis Control Program (OCP) in West Africa, based on a strongly nonlinear relation between vector mf uptake and human mf skin density previously published. However, observed levels of recrudescence have exceeded predictions, warranting a recalibration of the model. To this end, we present the results of a series of ßy-feeding experiments carried out in savanna and forest localities of West Africa. Flies belonging to Simulium damnosum s.s., S. sirbanum, S. soubrense, and S. leonense were fed on mf carriers and dissected to assess the number of ingested mf escaping imprisonment by the peritrophic matrix (the number of exo-peritrophic mf), a predictor of infective larval output. The method of instrumental variables was used to obtain (nearly) unbiased estimates of the parameters of interest, taking into account error in the measurement of skin mf density. This error is often neglected in these types of studies, making it difÞcult to ascertain the degree of density-dependence truly present in the relation between mf uptake and skin load. We conclude that this relation is weakly (yet signiÞcantly) nonlinear in savanna settings but indistinguishable from linearity in forest vectors. Exo-peritrophic mf uptake does not account for most of the density dependence in the transmission dynamics of the parasite as previously thought. The number of exo-mf in forest simuliids is at least Þve times higher than in the savanna vectors. Parasite abundance in human onchocerciasis is regulated by poorly known mechanisms operating mainly on other stages of the lifecycle.
Since 1987 onchocerciasis control has relied on the donation of ivermectin (Mectizan ® , Merck & ... more Since 1987 onchocerciasis control has relied on the donation of ivermectin (Mectizan ® , Merck & Co., Inc.) through the Mectizan Donation Programme. Recently, concern has been raised over the appearance of suboptimal responses to ivermectin in Ghana-highlighting the potential threat of the development of resistance to ivermectin. This report summarises a meeting held in Ghana to set the research agenda for future onchocerciasis control. The aim of this workshop was to define the research priorities for alternative drug and treatment regimes and control strategies to treat populations with existing evidence of suboptimal responsiveness and define research priorities for future control strategies in the event of the development of widespread ivermectin resistance.
To evaluate micro-haematuria, detected by Haemastix reagent strips, for diagnosis of urinary schi... more To evaluate micro-haematuria, detected by Haemastix reagent strips, for diagnosis of urinary schistosomiasis during a 3-year period of school-based control on Zanzibar. A sub-set of school children, from a total of 135,000 who were receiving treatment for urinary schistosomiasis and soil-transmitted helminthiasis, were monitored by parasitological and questionnaire methods for Schistosoma haematobium infections: at treatment baseline in 2004 (n=2002), follow up with re-treatment in 2005 (n=3278) and further follow up with re-treatment in 2006 (n=3993). Standard diagnostic scores for micro-haematuria were calculated against parasitological assessment. Diagnostic scores of Haemastix remained strong throughout the 3-year period. In 2006, scores were: sensitivity (SS)=0.86 (95% CI: 0.86-0.88), specificity (SP)=0.99 (0.98-1.00), positive predictive value (PPV)=0.90 (0.88-0.91), negative predictive value (NPV)=0.98 (0.98-0.99) in boys; and SS=0.84 (0.82-0.86), SP=0.98 (0.98-0.99), PPV=0.77 (0.75-0.79) and NPV=0.99 (0.99-1.00) in girls. By comparison, reported blood in urine and pain upon urination were much lower and not as informative. At a cost of approximately pound sterling 0.20/test, further use of reagent strips for monitoring of urinary schistosomiasis during ongoing control programmes should be advocated as a rapid, cost-effective and informative disease surveillance tool.
As part of a 4-year control programme beginning in 2003 and entitled Piga Vita Kichocho, around 1... more As part of a 4-year control programme beginning in 2003 and entitled Piga Vita Kichocho, around 140,000 school-aged children on Unguja Island, Zanzibar were treated annually with a combination of praziquantel and albendazole. To provide information on the impact of this intervention, a subset of children, originating from 24 sentinel schools, were monitored in 2004, 2005 and 2006 using both parasitological and behavioural questionnaire methods. Overall, prevalence of urinary schistosomiasis fell by 52%, intensity by 55% and gross haematuria by 82%. There was a positive and statistically significant correlation between areas of elevated disease prevalence and areas of predicted high transmission based upon local occurrence of the permissive intermediate snail host. In areas of low transmission, urinary schistosomiasis was greatly reduced, but, by contrast, other intervention strategies are needed to complement and synergise with chemotherapy in high transmission areas. Whereas significant reductions were documented in the prevalence of both Trichuris trichiura and hookworm, prevalence of Ascaris lumbricoides significantly increased over the monitoring period. Through a detailed analysis of named child records, evidence of predisposition to helminth (re)infection and individual bias towards polyparasitism was detected, highlighting the often overlapping distribution of these parasites within the school-aged child.
Bayesian statistical methods are increasingly being used in the analysis of parasitological data.... more Bayesian statistical methods are increasingly being used in the analysis of parasitological data. Here, the basis of differences between the Bayesian method and the classical or frequentist approach to statistical inference is explained. This is illustrated with practical implications ...
BACKGROUND: Since 1991, in Mexico, ivermectin has been administered twice a year to all residents... more BACKGROUND: Since 1991, in Mexico, ivermectin has been administered twice a year to all residents in the onchocerciasis endemic foci which are mainly located in the coffee growing areas. However, the presence of a potentially infected itinerant seasonal labour force which is not treated regularly could jeopardise the attainment of the 85% coverage which is the present target for elimination
Background: Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual)... more Background: Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual) ivermectin round. However, other modelling-based analyses suggest that ivermectin may not have such a cumulative effect. Uncertainty in this (biological) and other (programmatic) assumptions would affect projected outcomes of long-term ivermectin treatment. Methodology/Principal Findings: We modify a deterministic age-and sex-structured onchocerciasis transmission model, parameterised for savannah O. volvulus-Simulium damnosum, to explore the impact of assumptions regarding the effect of ivermectin on worm fertility and the patterns of treatment coverage compliance, and frequency on projections of parasitological outcomes due to long-term, mass ivermectin administration in hyperendemic areas. The projected impact of ivermectin distribution on onchocerciasis and the benefits of switching from annual to biannual distribution are strongly dependent on assumptions regarding the drug's effect on worm fertility and on treatment compliance. If ivermectin does not have a cumulative impact on microfilarial production, elimination of onchocerciasis in hyperendemic areas may not be feasible with annual ivermectin distribution. Conclusions/Significance: There is substantial (biological and programmatic) uncertainty surrounding modelling projections of onchocerciasis elimination. These uncertainties need to be acknowledged for mathematical models to inform control policy reliably. Further research is needed to elucidate the effect of ivermectin on O. volvulus reproductive biology and quantify the patterns of coverage and compliance in treated communities.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jun 21, 2016
Several African countries have adopted a biannual ivermectin distribution strategy in some foci ... more Several African countries have adopted a biannual ivermectin distribution strategy in some foci to control and eliminate onchocerciasis. In 2010, the Ghana Health Service started biannual distribution to combat transmission hotspots and sub-optimal responses to treatment. We assessed the epidemiological impact of the first 3 years of this strategy and quantified responses to ivermectin over two consecutive rounds of treatment in 10 sentinel communities. We evaluated Onchocerca volvulus microfilarial intensity and prevalence in those aged ≥20 years before the first, second and fifth (or sixth) biannual treatment rounds using skin snip data from 956 participants. We used longitudinal regression modelling to estimate rates of microfilarial repopulation of the skin in a cohort of 217 participants who were followed-up over the first two rounds of biannual treatment. Biannual treatment has had a positive impact, with substantial reductions in infection intensity after 4 or 5 rounds in ...
Recognising the burden helminth infections impose on human populations, and particularly the poor... more Recognising the burden helminth infections impose on human populations, and particularly the poor, major intervention programmes have been launched to control onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, and cysticercosis. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research
To develop a Bayesian hierarchical model for human onchocerciasis with which to explore the facto... more To develop a Bayesian hierarchical model for human onchocerciasis with which to explore the factors that influence prevalence of microfilariae in the Amazonian focus of onchocerciasis and predict the probability of any community being at least mesoendemic (>20% prevalence of microfilariae), and thus in need of priority ivermectin treatment. Models were developed with data from 732 individuals aged > or =15 years who lived in 29 Yanomami communities along four rivers of the south Venezuelan Orinoco basin. The models' abilities to predict prevalences of microfilariae in communities were compared. The deviance information criterion, Bayesian P-values, and residual values were used to select the best model with an approximate cross-validation procedure. A three-level model that acknowledged clustering of infection within communities performed best, with host age and sex included at the individual level, a river-dependent altitude effect at the community level, and additional c...
It is well documented that the density of Plasmodium in its vertebrate host modulates the physiol... more It is well documented that the density of Plasmodium in its vertebrate host modulates the physiological response induced; this in turn regulates parasite survival and transmission. It is less clear that parasite density in the mosquito regulates survival and transmission of this important pathogen. Numerous studies have described conversion rates of Plasmodium from one life stage to the next within the mosquito, yet few have considered that these rates might vary with parasite density. Here we establish infections with defined numbers of the rodent malaria parasite Plasmodium berghei to examine how parasite density at each stage of development (gametocytes; ookinetes; oocysts and sporozoites) influences development to the ensuing stage in Anopheles stephensi, and thus the delivery of infectious sporozoites to the vertebrate host. We show that every developmental transition exhibits strong density dependence, with numbers of the ensuing stages saturating at high density. We further show that when fed ookinetes at very low densities, oocyst development is facilitated by increasing ookinete number (i.e., the efficiency of ookinete-oocyst transformation follows a sigmoid relationship). We discuss how observations on this model system generate important hypotheses for the understanding of malaria biology, and how these might guide the rational analysis of interventions against the transmission of the malaria parasites of humans by their diverse vector species. Citation: Sinden RE, Dawes EJ, Alavi Y, Waldock J, Finney O, et al. (2007) Progression of Plasmodium berghei through Anopheles stephensi is density-dependent. PLoS Pathog 3(12): e195.
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Papers by Margarita As