Summary Background Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two ...pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to clear the transmissible stage of the helminth completely in treated individuals. The aim of this study was to use modelling to assess the potential value of mass drug administration with the triple-drug regimen for accelerating elimination of lymphatic filariasis in different epidemiological settings. Methods We used three different transmission models to compare the number of rounds of mass drug administration needed to achieve a prevalence of microfilaraemia less than 1% with the triple-drug regimen and with current two-drug regimens. Findings In settings with a low baseline prevalence of lymphatic filariasis (5%), the triple-drug regimen reduced the number of rounds of mass drug administration needed to reach the target prevalence by one or two rounds, compared with the two-drug regimen. For areas with higher baseline prevalence (10–40%), the triple-drug regimen strikingly reduced the number of rounds of mass drug administration needed, by about four or five, but only at moderate-to-high levels of population coverage (>65%) and if systematic non-adherence to mass drug administration was low. Interpretation Simulation modelling suggests that the triple-drug regimen has potential to accelerate the elimination of lymphatic filariasis if high population coverage of mass drug administration can be achieved and if systematic non-adherence with mass drug administration is low. Future work will reassess these estimates in light of more clinical trial data and to understand the effect on an individual country's programme. Funding Bill & Melinda Gates Foundation.
•Novel methodology for combining geostatistical mapping and transmission modelling.•Guide the planning of spatial control programmes by identifying affected areas.•Current intervention strategy will ...not be sufficient to eliminate LF in most areas.•Alternative strategies will be required to accelerate LF elimination in East Africa.
Infectious diseases remain one of the major causes of human mortality and suffering. Mathematical models have been established as an important tool for capturing the features that drive the spread of the disease, predicting the progression of an epidemic and hence guiding the development of strategies to control it. Another important area of epidemiological interest is the development of geostatistical methods for the analysis of data from spatially referenced prevalence surveys. Maps of prevalence are useful, not only for enabling a more precise disease risk stratification, but also for guiding the planning of more reliable spatial control programmes by identifying affected areas. Despite the methodological advances that have been made in each area independently, efforts to link transmission models and geostatistical maps have been limited. Motivated by this fact, we developed a Bayesian approach that combines fine-scale geostatistical maps of disease prevalence with transmission models to provide quantitative, spatially-explicit projections of the current and future impact of control programs against a disease. These estimates can then be used at a local level to identify the effectiveness of suggested intervention schemes and allow investigation of alternative strategies. The methodology has been applied to lymphatic filariasis in East Africa to provide estimates of the impact of different intervention strategies against the disease.
In January 2021, the World Health Organization published the 2021-2030 roadmap for the control of neglected tropical diseases (NTDs). The goal for schistosomiasis is to achieve elimination as a ...public health problem (EPHP) and elimination of transmission (EOT) in 78 and 25 countries (by 2030), respectively. Mass drug administration (MDA) of praziquantel continues to be the main strategy for control and elimination. However, as there is limited availability of praziquantel, it is important to determine what volume of treatments are required, who should be targeted and how frequently treatment must be administered to eliminate either transmission or morbidity caused by infection in different endemic settings with varied transmission intensities. METHODS AND RESULTS: In this paper, we employ two individual-based stochastic models of schistosomiasis transmission developed independently by the Imperial College London (ICL) and University of Oxford (SCHISTOX) to determine the optimal treatment strategies to achieve EOT. We find that treating school-age children (SAC) only is not sufficient to achieve EOT within a feasible time frame, regardless of the transmission setting and observed age-intensity of infection profile. Both models show that community-wide treatment is necessary to interrupt transmission in all endemic settings with low, medium and high pristine transmission intensities.
The required MDA coverage level to achieve either transmission or morbidity elimination depends on the prevalence prior to the start of treatment and the burden of infection in adults. The higher the worm burden in adults, the higher the coverage levels required for this age category through community-wide treatment programmes. Therefore, it is important that intensity and prevalence data are collected in each age category, particularly from SAC and adults, so that the correct coverage level can be calculated and administered.
It is well known that individuals in the same community can be exposed to a highly variable number of mosquito bites. This heterogeneity in bite exposure has consequences for the control of ...vector-borne diseases because a few people may be contributing significantly to transmission. However, very few studies measure sources of heterogeneity in a way which is relevant to decision-making. We investigate the relationship between two classic measures of heterogeneity, spatial and individual, within the context of lymphatic filariasis, a parasitic mosquito-borne disease. Using infection and mosquito-bite data for five villages in Papua New Guinea, we measure biting characteristics to model what impact bed-nets have had on control of the disease. We combine this analysis with geospatial modelling to understand the spatial relationship between disease indicators and nightly mosquito bites. We found a weak association between biting and infection heterogeneity within villages. The introduction of bed-nets increased biting heterogeneity, but the reduction in mean biting more than compensated for this, by reducing prevalence closer to elimination thresholds. Nightly biting was explained by a spatial heterogeneity model, while parasite load was better explained by an individual heterogeneity model. Spatial and individual heterogeneity are qualitatively different with profoundly different policy implications.
High HIV-1 plasma viral loads (PVLs) in sub-Saharan Africa, partly because of high rates of coinfection, may have been one of the drivers of the "explosive" epidemics seen in that region. Using a ...previously published framework of infectiousness and survival, we estimate the excess onward HIV-1 transmission events (secondary infections) resulting from coinfection-induced changes in PVL during asymptomatic HIV-1 infection. For every 100 HIV-infected people, each suffering 1 episode of tuberculosis infection, there are 4.9 (2.7th-97.5th percentile: 0.2-21.5) excess onward HIV-1 transmission events attributable to this coinfection. Other estimates are malaria 0.4 (0.0-2.0), soil-transmitted helminths 3.1 (0.1-14.9), schistosomiasis 8.5 (0.2-38.6), filariasis 13.3 (0.3-89.2), syphilis 0.1 (0.0-1.6), herpes simplex virus 4.0 (0.0-24.2), and gonorrhea 2.1 (0.1-8.0) transmissions. If these higher PVLs confer a shorter life expectancy and higher infectiousness, then their impact on transmission is, in general, reduced. For most HIV-1 coinfections, the duration of a single infection is too short and/or the associated PVL elevation is too modest to contribute substantially to onward HIV-1 transmission.
Abstract
Background
The 2030 goal for schistosomiasis is elimination as a public health problem (EPHP), with mass drug administration (MDA) of praziquantel to school-age children (SAC) as a central ...pillar of the strategy. However, due to coronavirus disease 2019, many mass treatment campaigns for schistosomiasis have been halted, with uncertain implications for the programmes.
Methods
We use mathematical modelling to explore how postponement of MDA and various mitigation strategies affect achievement of the EPHP goal for Schistosoma mansoni and S. haematobium.
Results
For both S. mansoni and S. haematobium in moderate- and some high-prevalence settings, the disruption may delay the goal by up to 2 y. In some high-prevalence settings, EPHP is not achievable with current strategies and so the disruption will not impact this. Here, increasing SAC coverage and treating adults can achieve the goal. The impact of MDA disruption and the appropriate mitigation strategy varies according to the baseline prevalence prior to treatment, the burden of infection in adults and the stage of the programme.
Conclusions
Schistosomiasis MDA programmes in medium- and high-prevalence areas should restart as soon as is feasible and mitigation strategies may be required in some settings.
Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent ...and case-finding-based interventions rarely target asymptomatic individuals.
We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases.
We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission.
Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.
Abstract
The early termination of the Accelerating the Sustainable Control and Elimination of Neglected Tropical Diseases (Ascend) programme by the UK government in June 2021 was a bitter blow to ...countries in East and West Africa where no alternative source of funding existed. Here we assess the potential impact the cuts may have had if alternative funding had not been made available by new development partners and outline new strategies developed by affected countries to mitigate current and future disruptions to neglected tropical disease control programmes.
The London Declaration on neglected tropical diseases was based in part on a new World Health Organization roadmap to "sustain, expand and extend drug access programmes to ensure the necessary supply ...of drugs and other interventions to help control by 2020". Large drug donations from the pharmaceutical industry form the backbone to this aim, especially for soil-transmitted helminths (STHs) raising the question of how best to use these resources. Deworming for STHs is often targeted at school children because they are at greatest risk of morbidity and because it is remarkably cost-effective. However, the impact of school-based deworming on transmission in the wider community remains unclear.
We first estimate the proportion of parasites targeted by school-based deworming using demography, school enrolment, and data from a small number of example settings where age-specific intensity of infection (either worms or eggs) has been measured for all ages. We also use transmission models to investigate the potential impact of this coverage on transmission for different mixing scenarios.
In the example settings <30% of the population are 5 to <15 years old. Combining this demography with the infection age-intensity profile we estimate that in one setting school children output as little as 15% of hookworm eggs, whereas in another setting they harbour up to 50% of Ascaris lumbricoides worms (the highest proportion of parasites for our examples). In addition, it is estimated that from 40-70% of these children are enrolled at school.
These estimates suggest that, whilst school-based programmes have many important benefits, the proportion of infective stages targeted by school-based deworming may be limited, particularly where hookworm predominates. We discuss the consequences for transmission for a range of scenarios, including when infective stages deposited by children are more likely to contribute to transmission than those from adults.
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