Control of onchocerciasis in Africa: threshold shifts, breakpoints and rules for elimination

Control of onchocerciasis in Africa is currently based on annual community-directed treatment with ivermectin (CDTI) which has been assumed to be not efficient enough to bring about elimination. However, elimination has recently been reported to have been achieved by CDTI alone in villages of Senegal and Mali, reviving debate on the eradicability of onchocerciasis in Africa. We investigate the eradicability of onchocerciasis by examining threshold shifts and breakpoints predicted by a stochastic transmission model that has been fitted extensively to data. We show that elimination based on CDTI relies on shifting the threshold biting rate to a level that is higher than the annual biting rate. Breakpoints become relevant in the context of when to stop CDTI. In order for the model to predict a good chance for CDTI to eliminate onchocerciasis, facilitating factors such as the macrofilaricidal effect of ivermectin must be assumed. A chart predicting the minimum efficacy of CDTI required for elimination, dependent on the annual biting rate, is provided. Generalisable recommendations into strategies for the elimination of onchocerciasis are derived, particularly referring to the roles of vectors, the residual infection rate under control, and a low-spreader problem originating from patients with low parasite burdens.     

Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.     

Population biology of human onchocerciasis.

Human onchocerciasis (river blindness) is the filarial infection caused by Onchocerca volvulus and transmitted among people through the bites of the Simulium vector. Some 86 million people around the world are at risk of acquiring the nematode, with 18 million people infected and 600,000 visually impaired, half of them partially or totally blind. 99% of cases occur in tropical Africa; scattered foci exist in Latin America. Until recently control programmes, in operation since 1975, have consisted of antivectorial measures. With the introduction of ivermectin in 1988, safe and effective chemotherapy is now available. With the original Onchocerciasis Control Programme of West Africa coming to an end, both the new African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas, rely heavily on ivermectin self-sustained mass delivery. In consequence, the need for understanding the processes regulating parasite abundance in human and simuliid populations is of utmost importance. We present a simple mathematical framework built around recent analyses of exposure- and density-dependent processes operating, respectively, within the human and vector hosts. An expression for the basic reproductive ratio, R0, is derived and related to the minimum vector density required for parasite persistence in localities of West Africa in general and northern Cameroon in particular. Model outputs suggest that constraints acting against parasite establishment in both humans and vectors are necessary to reproduce field observations, but those in humans may not fully protect against reinfection. Analyses of host age-profiles of infection prevalence, intensity, and aggregation for increasing levels of endemicity and intensity of transmission in the Vina valley of northern Cameroon are in agreement with these results and discussed in light of novel work on onchocerciasis immunology.     

The impact of ivermectin on onchocerciasis in villages co-endemic for lymphatic filariasis in an area of onchocerciasis recrudescence in Burkina Faso

In Burkina Faso, onchocerciasis was no longer a public health problem when the WHO Onchocerciasis Control Programme in West Africa closed at the end in 2002. However, epidemiological surveillance carried out from November 2010 to February of 2011, showed a recrudescence of infection in the Cascades Region. This finding was made at a time when ivermectin, a drug recommended for the treatment of both onchocerciasis and lymphatic filariasis, had been distributed in this area since 2004 for the elimination of lymphatic filariasis. It was surprising that ivermectin distributed for treating lymphatic filariasis had not prevented the recrudescence of onchocerciasis. Faced with this situation, the aim of our study was to evaluate the effectiveness of ivermectin on the onchocerciasis parasite. The percentage reduction in microfilarial load after treatment with ivermectin was used as a proxy measure for assessing possible resistance. A cohort study was carried out with 130 individuals who had tested positive for microfilariae of Onchocerca volvulus in 2010 using microscopic examination of skin-snip biopsies from five endemic villages. Subjects were followed from July 2011 to June 2012. The microfilarial load of each individual was enumerated by skin-snip biopsy in 2010, prior to the first ivermectin treatment against onchocerciasis under community guidelines. All individuals received two ivermectin treatments six months apart. In 2012, the microfilarial loads were determined again, six months after the second round of ivermectin and the reductions in parasite loads were calculated to measure the impact of the drug. The percentage reduction of the microfilarial loads ranged from 87% to 98% in the villages. In all villages, there was a statistically significant difference between the average microfilarial loads in 2010 and 2012. The level of reduction of microfilarial loads suggests that ivermectin is effective against the recrudescent population of O. volvulus in Cascades Region of Burkina Faso. Further investigations would be necessary to determine the causes of the recrudescence of onchocerciasis. (For French language abstract, see S1 Alternative Language Abstract—Translation of the Abstract into French by the authors.)     

Seasonal Variation in Biting Rates of Simulium damnosum sensu lato,Vector of Onchocerca volvulus,in Two Sudanese Foci

Background

The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR) and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs.

Methods

A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007–2008 and 2009–2010). Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests.

Results

Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies) than Galabat (8,202 flies). In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month), and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month) while none of flies were collected in August-October (MBR = 0 bites/person/month). In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month) and September 2010 (N = 1,163, MBR = 6,978 bites/person/month), whereas, none appeared in collection from April to June. There was a significant difference in mean monthly density of S. damnosum s.l. across the two foci in 2007–2008 (df = 3, F = 3.91, P = 0.011). Minimum temperature showed significant correlation with adult flies counts in four areas sampled; the adult counts were increased in Nady village (r_s = 0.799) and were decreased in Kalasecal (r_s = - 0.676), Gumaiza (r_s = - 0.585), and Hilat Khateir (r_s = - 0.496). Maximum temperature showed positive correlation with black fly counts only in Galabat focus. Precipitation was significantly correlated with adult flies counts in Nady village, Abu-Hamed, but no significance was found in the rest of the sampled villages in both foci. Hourly-based distribution of black flies showed a unimodal pattern in Abu-Hamed with one peak (10:00–18:00), while a bimodal pattern with two peaks (07:00–10:00) and (14:00–18:00) was exhibited in Galabat.

Conclusion

Transmission of onchocerciasis in both foci showed marked differences in seasonality, which may be attributed to ecology, microclimate and proximity of breeding sites to collection sites. The seasonal shifts between the two foci might be related to variations in climate zones. This information on black fly vector seasonality, ecology, distribution and biting activity has obvious implications in monitoring transmission levels to guide the national and regional onchocerciasis elimination programs in Sudan.     

Validation of onchocerciasis biomarker N-acetyltyramine-O-glucuronide (NATOG)

The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG’s biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development.     

Control of onchocerciasis today: status and challenges

The filarid parasite Onchocerca volvulus is the causative agent of human onchocerciasis (river blindness), an infection characterized by chronic skin and eye lesions. There are three regional programs currently dedicated to controlling onchocerciasis in the endemic areas of Africa and the Americas: the Onchocerciasis Control Programme of West Africa, the African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Program for the Americas. All three programs use periodic mass treatment with the microfilaricidal drug ivermectin with differing strategic purposes and, as a result, face different challenges to reach their goals. This paper will review the strategies, status and challenges of these three programs.     

Reducing Plasmodium falciparum Malaria Transmission in Africa: A Model-Based Evaluation of Intervention Strategies

Background

Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools.

Methods and Findings

We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector–species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR∼3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained. In two of the moderate-transmission settings (EIR∼43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR∼586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels.

Conclusions

Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required. Please see later in the article for the Editors'' Summary     

The impact of mass drug administration expansion to low onchocerciasis prevalence settings in case of connected villages

BackgroundThe existence of locations with low but stable onchocerciasis prevalence is not well understood. An often suggested yet poorly investigated explanation is that the infection spills over from neighbouring locations with higher infection densities.MethodologyWe adapted the stochastic individual based model ONCHOSIM to enable the simulation of multiple villages, with separate blackfly (intermediate host) and human populations, which are connected through the regular movement of the villagers and/or the flies. With this model we explore the impact of the type, direction and degree of connectedness, and of the impact of localized or full-area mass drug administration (MDA) over a range of connected village settings.Principal findingsIn settings with annual fly biting rates (ABR) below the threshold needed for stable local transmission, persistence of onchocerciasis prevalence can well be explained by regular human traffic and/or fly movement from locations with higher ABR. Elimination of onchocerciasis will then theoretically be reached by only implementing MDA in the higher prevalence area, although lingering infection in the low prevalence location can trigger resurgence of transmission in the total region when MDA is stopped too soon. Expanding MDA implementation to the lower ABR location can therefore shorten the duration of MDA needed. For example, when prevalence spill-over is due to human traffic, and both locations have about equal populations, then the MDA duration can be shortened by up to three years. If the lower ABR location has twice as many inhabitants, the reduction can even be up to six years, but if spill-over is due to fly movement, the expected reduction is less than a year.Conclusions/SignificanceAlthough MDA implementation might not always be necessary in locations with stable low onchocerciasis prevalence, in many circumstances it is recommended to accelerate achieving elimination in the wider area.     

Outstanding insecurities concerning the use of an Ov16-based ELISA in the Amazonia onchocerciasis focus

In a recent issue of Memórias do Instituto Oswaldo Cruz, published in Rio de Janeiro in February 2014 (109: 87-92), Adami et al. have published a survey reporting Mansonella parasite prevalence in the Amazon Region. This report makes a useful contribution to the existing knowledge of filarial parasite distribution within the Amazon area, parasite prevalence rates in relation to age and occupation and provides observations on the possible clinical impact of Mansonella ozzardi. Their publication also provides an account of what appears to be a novel ELISA that has recently been used in the Simuliidae and Onchocerciasis Laboratory of the Oswaldo Cruz Institute, Rio de Janeiro, Brazil. We are concerned that the publication of this ELISA may have created an excessively positive impression of the effectiveness of the onchocerciasis recrudescence serological surveillance tools that are presently available for use in the Amazonia onchocerciasis focus. In this letter we have, thus, sought to highlight some of the limitations of this ELISA and suggest how continuing insecurities concerning the detection of antibodies to Onchocerca volvulus within the Amazonia onchocerciasis focus might be minimised.     

Proof-of-Principle of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: Final Results of a Study in Mali and Senegal

Background

Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment.

Methodology/Principal Findings

Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination.

Conclusion/Significance

The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.     

Mass drug treatment for lymphatic filariasis and onchocerciasis

This review summarizes the progress towards control of lymphatic filariasis (LF) and onchocerciasis, focussing on the impact of mass drug administration (MDA) programmes, in particular those that have developed following the donation of ivermectin and albendazole. The contrasting strategies and objectives of the different programmes are compared, and the impact on transmission, clinical disease and public health assessed. The constraints on programme success are: (i) the absence of a macrofilaricide, which can be used in a public health context; (ii) the sustainability of high coverage of ivermectin over many years in onchocerciasis control; and (iii) the problem of treatment in areas where Loa loa (tropical eye worm) is co-endemic with onchocerciasis because of the rare severe adverse events. LF programmes are expanding rapidly in over 30 countries, where circa 60 million people received treatments in 2002. No serious adverse events have been associated with MDAs for LF elimination. Research on new approaches to treatment using antibiotics are showing promising results in pilot settings because doxycyline has been shown to have long-term embryostatic effects and sustained reductions of microfilaria loads in onchocerciasis and bancroftian filariasis.     

Density-dependent mortality of the human host in onchocerciasis: relationships between microfilarial load and excess mortality

Background

The parasite Onchocerca volvulus has, until recently, been regarded as the cause of a chronic yet non-fatal condition. Recent analyses, however, have indicated that in addition to blindness, the parasite can also be directly associated with human mortality. Such analyses also suggested that the relationship between microfilarial load and excess mortality might be non-linear. Determining the functional form of such relationship would contribute to quantify the population impact of mass microfilaricidal treatment.

Methodology/Principal Findings

Data from the Onchocerciasis Control Programme in West Africa (OCP) collected from 1974 through 2001 were used to determine functional relationships between microfilarial load and excess mortality of the human host. The goodness-of-fit of three candidate functional forms (a (log-) linear model and two saturating functions) were explored and a saturating (log-) sigmoid function was deemed to be statistically the best fit. The excess mortality associated with microfilarial load was also found to be greater in younger hosts. The attributable mortality risk due to onchocerciasis was estimated to be 5.9%.

Conclusions/Significance

Incorporation of this non-linear functional relationship between microfilarial load and excess mortality into mathematical models for the transmission and control of onchocerciasis will have important implications for our understanding of the population biology of O. volvulus, its impact on human populations, the global burden of disease due to onchocerciasis, and the projected benefits of control programmes in both human and economic terms.     

Impact of ivermectin on onchocerciasis transmission: assessing the empirical evidence that repeated ivermectin mass treatments may lead to elimination/eradication in West-Africa

BACKGROUND: The Onchocerciasis Control Program (OCP) in West Africa has been closed down at the end of 2002. All subsequent control will be transferred to the participating countries and will almost entirely be based on periodic mass treatment with ivermectin. This makes the question whether elimination of infection or eradication of onchocerciasis can be achieved using this strategy of critical importance. This study was undertaken to explore this issue. METHODS: An empirical approach was adopted in which a comprehensive analysis was undertaken of available data on the impact of more than a decade of ivermectin treatment on onchocerciasis infection and transmission. Relevant entomological and epidemiological data from 14 river basins in the OCP and one basin in Cameroon were reviewed. Areas were distinguished by frequency of treatment (6-monthly or annually), endemicity level and additional control measures such as vector control. Assessment of results were in terms of epidemiological and entomological parameters, and as a measure of inputs, therapeutic and geographical coverage rates were used. RESULTS: In all of the river basins studied, ivermectin treatment sharply reduced prevalence and intensity of infection. Significant transmission, however, is still ongoing in some basins after 10-12 years of ivermectin treatment. In other basins, transmission may have been interrupted, but this needs to be confirmed by in-depth evaluations. In one mesoendemic basin, where 20 rounds of four-monthly treatment reduced prevalence of infection to levels as low as 2-3%, there was significant recrudescence of infection within a few years after interruption of treatment. CONCLUSIONS: Ivermectin treatment has been very successful in eliminating onchocerciasis as a public health problem. However, the results presented in this paper make it almost certain that repeated ivermectin mass treatment will not lead to the elimination of transmission of onchocerciasis from West Africa. Data on 6-monthly treatments are not sufficient to draw definitive conclusions.     

The relationships between the burden of adult parasites, host age and the microfilarial density in human onchocerciasis

We investigate the relationship between the microfilarial density in the skin and the burden of adult female Onchocerca volvulus by analysing pre-control nodulectomy data which allow for a direct approach, independent of exposure. The data of 169 patients in Burkina Faso and 182 patients in Liberia represent savannah and forest onchocerciasis in West Africa, respectively. Whereas in Burkina Faso, a saturating relationship between microfilarial density and worm burden suggests the operation of density-dependent processes within human hosts, the Liberian data show a linear relationship implying no density dependence. The differences may derive from differences between both parasite strains, i.e. the savannah or the forest strain of O. volvulus. Consistently for both parasite strains and independent of the worm burden, the microfilarial density increases with host age emphasising the concept of the acquisition of immunological tolerance. In male hosts in Liberia, the microfilarial density increases stronger with the worm burden than in female hosts, whereas such sex-specific differences cannot be found in Burkina Faso. In the methodological part of this investigation, we suggest the beta-distribution to be most appropriate for describing variability in microfilarial densities and we present an approach to consider the uncertainty in the adult parasite burden which cannot be determined precisely in helminth infections. Implications of density dependence are discussed with respect to immunological processes in the human host and with respect to the success of control programs. The relationships described show that regulatory processes between the parasite and the human host are multi-dimensional, operating within a high degree of biological variability.     

Statistical Properties of Parasite Density Estimators in Malaria

Malaria is a global health problem responsible for nearly one million deaths every year around 85% of which concern children younger than five years old in Sub-Saharan Africa. In addition, around million clinical cases are declared every year. The level of infection, expressed as parasite density, is classically defined as the number of asexual parasites relative to a microliter of blood. Microscopy of Giemsa-stained thick blood films is the gold standard for parasite enumeration. Parasite density estimation methods usually involve threshold values; either the number of white blood cells counted or the number of high power fields read. However, the statistical properties of parasite density estimators generated by these methods have largely been overlooked. Here, we studied the statistical properties (mean error, coefficient of variation, false negative rates) of parasite density estimators of commonly used threshold-based counting techniques depending on variable threshold values. We also assessed the influence of the thresholds on the cost-effectiveness of parasite density estimation methods. In addition, we gave more insights on the behavior of measurement errors according to varying threshold values, and on what should be the optimal threshold values that minimize this variability.     

Human Onchocerciasis: Modelling the Potential Long-term Consequences of a Vaccination Programme

Background

Currently, the predominant onchocerciasis control strategy in Africa is annual mass drug administration (MDA) with ivermectin. However, there is a consensus among the global health community, supported by mathematical modelling, that onchocerciasis in Africa will not be eliminated within proposed time frameworks in all endemic foci with only annual MDA, and novel and alternative strategies are urgently needed. Furthermore, use of MDA with ivermectin is already compromised in large areas of central Africa co-endemic with Loa loa, and there are areas where suboptimal or atypical responses to ivermectin have been documented. An onchocerciasis vaccine would be highly advantageous in these areas.

Methodology/Principal Findings

We used a previously developed onchocerciasis transmission model (EPIONCHO) to investigate the impact of vaccination in areas where loiasis and onchocerciasis are co-endemic and ivermectin is contraindicated. We also explore the potential influence of a vaccination programme on infection resurgence in areas where local elimination has been successfully achieved. Based on the age range included in the Expanded Programme on Immunization (EPI), the vaccine was assumed to target 1 to 5 year olds. Our modelling results indicate that the deployment of an onchocerciasis vaccine would have a beneficial impact in onchocerciasis–loiasis co-endemic areas, markedly reducing microfilarial load in the young (under 20 yr) age groups.

Conclusions/Significance

An onchocerciasis prophylactic vaccine would reduce the onchocerciasis disease burden in populations where ivermectin cannot be administered safely. Moreover, a vaccine could substantially decrease the chance of re-emergence of Onchocerca volvulus infection in areas where it is deemed that MDA with ivermectin can be stopped. Therefore, a vaccine would protect the substantial investments made by present and past onchocerciasis control programmes, decreasing the chance of disease recrudescence and offering an important additional tool to mitigate the potentially devastating impact of emerging ivermectin resistance.     

Models for the population biology and control of human onchocerciasis

The absence of animal models in which to reproduce successfully the complete life cycle of Onchocerca volvulus has hindered progress towards unravelling the processes involved in the regulation of parasite abundance in the vertebrate host. Mathematical frameworks have been developed to explore the consequences of such processes in determining parasite population dynamics and the effect on these of control interventions. Post-control predictions are strongly influenced by the assumptions concerning the reproductive life span of the adult female worm (the longest-lived parasite stage) and the distribution of its survival times, and this notion is important to all frameworks. Here, we review the development of models concerning onchocerciasis and discuss the various approaches that have been used, presenting a deterministic framework with parameter values estimated from the Mexican onchocerciasis control programme. This model is used to evaluate interventions combining the removal of adult worms (nodulectomy) and the microfilaricidal and possibly sterilizing effect of ivermectin.     

Evaluation of a Community-Based Trapping Program to Collect Simulium ochraceum sensu lato for Verification of Onchocerciasis Elimination

Background

Collection of the black fly vectors of onchocerciasis worldwide relies upon human landing collections. Recent studies have suggested that the Esperanza Window Trap baited with a human scent lure and CO₂ had the potential to replace human hosts for the collection of Simulium ochraceum sensu lato in Southern Chiapas focus, Mexico. The feasibility of utilizing these traps in a community-based approach for the collection of S. ochraceum s.l. was evaluated.

Methodology/Principal findings

Local residents of a formerly endemic extra-sentinel community for onchocerciasis were trained to carry out collections using the traps. The residents operated the traps over a 60-day period and conducted parallel landing collections, resulting in a total of 28,397 vector black flies collected. None of the flies collected were found to contain parasite DNA when tested by a polymerase chain reaction assay targeting a parasite specific sequence, resulting in a point estimate of infection in the vectors of zero, with an upper bound of the 95% confidence interval 0.13 per 2,000. This meets the accepted criterion for demonstrating an interruption of parasite transmission.

Conclusions/Significance

These data demonstrate that Esperanza Window Traps may be effectively operated by minimally trained residents of formerly endemic communities, resulting in the collection of sufficient numbers of flies to verify transmission interruption of onchocerciasis. The traps represent a viable alternative to using humans as hosts for the collection of vector flies as part of the verification of onchocerciasis elimination.     

Treatment of onchocerciasis with ivermectin in Sierra Leone

Ivermectin chemotherapy is proving to be a major advance in the management of onchocerciasis. In this article, James Whitworth reviews the work done on onchocerciasis and ivermectin in Sierra Leone and examines the evidence that mass treatment might control the clinical features of the disease and its transmission in West Africa. Ivermectin is safe and effectively reduces microfilarial (mf) loads, with major improvement in some ocular manifestations o f disease. This alone makes mass distribution to communities at risk of blindness worthwhile, even though the impact on other clinical features is less clear cut. Repeated doses have a cumulative effect on adult worms, which may cause more reduction in transmission than hitherto thought likely.