Evaluating elimination thresholds and stopping criteria for interventions against the vector-borne macroparasitic disease, lymphatic filariasis, using mathematical modelling.
Ontology highlight
ABSTRACT:
SUBMITTER: Sharma S
PROVIDER: S-EPMC9971242 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
Publications
Evaluating elimination thresholds and stopping criteria for interventions against the vector-borne macroparasitic disease, lymphatic filariasis, using mathematical modelling.
Sharma Swarnali S Smith Morgan E ME Bilal Shakir S Michael Edwin E
Communications biology 20230227 1
We leveraged the ability of EPIFIL transmission models fit to field data to evaluate the use of the WHO Transmission Assessment Survey (TAS) for supporting Lymphatic Filariasis (LF) intervention stopping decisions. Our results indicate that understanding the underlying parasite extinction dynamics, particularly the protracted transient dynamics involved in shifts to the extinct state, is crucial for understanding the impacts of using TAS for determining the achievement of LF elimination. These f ...[more]
Similar Datasets
Project description:BackgroundThe current global efforts to control the morbidity and mortality caused by infectious diseases affecting developing countries--such as HIV/AIDS, polio, tuberculosis, malaria and the Neglected Tropical Diseases (NTDs)-have led to an increasing focus on the biological controllability or eradicability of disease transmission by management action. Here, we use an age-structured dynamical model of lymphatic filariasis transmission to show how a quantitative understanding of the dynamic processes underlying infection persistence and extinction is key to evaluating the eradicability of this macroparasitic disease.Methodology/principal findingsWe investigated the persistence and extinction dynamics of lymphatic filariasis by undertaking a numerical equilibrium analysis of a deterministic model of parasite transmission, based on varying values of the initial L3 larval density in the system. The results highlighted the likely occurrence of complex dynamics in parasite transmission with three major outcomes for the eradicability of filariasis. First, both vector biting and worm breakpoint thresholds are shown to be complex dynamic entities with values dependent on the nature and magnitude of vector-and host specific density-dependent processes and the degree of host infection aggregation prevailing in endemic communities. Second, these thresholds as well as the potential size of the attractor domains and hence system resilience are strongly dependent on peculiarities of infection dynamics in different vector species. Finally, the existence of multiple stable states indicates the presence of hysteresis nonlinearity in the filariasis system dynamics in which infection thresholds for infection invasion are lower but occur at higher biting rates than do the corresponding thresholds for parasite elimination.Conclusions/significanceThe variable dynamic nature of thresholds and parasite system resilience reflecting both initial conditions and vector species-infection specificities, and the existence of hysteresis loop phenomenon, suggests that eradication of filariasis may require taking a more flexible and locally relevant approach to designing elimination programmes compared to the current command and control approach advocated by the global programme.
| S-EPMC2518518 | biostudies-literature
Project description:BackgroundLarge-scale intervention programmes to control or eliminate several infectious diseases are currently underway worldwide. However, a major unresolved question remains: what are reasonable stopping points for these programmes? Recent theoretical work has highlighted how the ecological complexity and heterogeneity inherent in the transmission dynamics of macroparasites can result in elimination thresholds that vary between local communities. Here, we examine the empirical evidence for this hypothesis and its implications for the global elimination of the major macroparasitic disease, lymphatic filariasis, by applying a novel Bayesian computer simulation procedure to fit a dynamic model of the transmission of this parasitic disease to field data from nine villages with different ecological and geographical characteristics. Baseline lymphatic filariasis microfilarial age-prevalence data from three geographically distinct endemic regions, across which the major vector populations implicated in parasite transmission also differed, were used to fit and calibrate the relevant vector-specific filariasis transmission models. Ensembles of parasite elimination thresholds, generated using the Bayesian fitting procedure, were then examined in order to evaluate site-specific heterogeneity in the values of these thresholds and investigate the ecological factors that may underlie such variabilityResultsWe show that parameters of density-dependent functions relating to immunity, parasite establishment, as well as parasite aggregation, varied significantly between the nine different settings, contributing to locally varying filarial elimination thresholds. Parasite elimination thresholds predicted for the settings in which the mosquito vector is anopheline were, however, found to be higher than those in which the mosquito is culicine, substantiating our previous theoretical findings. The results also indicate that the probability that the parasite will be eliminated following six rounds of Mass Drug Administration with diethylcarbamazine and albendazole decreases markedly but non-linearly as the annual biting rate and parasite reproduction number increases.ConclusionsThis paper shows that specific ecological conditions in a community can lead to significant local differences in population dynamics and, consequently, elimination threshold estimates for lymphatic filariasis. These findings, and the difficulty of measuring the key local parameters (infection aggregation and acquired immunity) governing differences in transmission thresholds between communities, mean that it is necessary for us to rethink the utility of the current anticipatory approaches for achieving the elimination of filariasis both locally and globally.
| S-EPMC2848205 | biostudies-literature
Project description:BackgroundMass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires <2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole.Methodolgy/principal findingsWe verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ population, and determined safe (>95% positive predictive value) thresholds for stopping MDA. The model captured trends in Mf and CFA prevalences reasonably well. Elimination cannot be predicted with sufficient certainty from CFA prevalence in 6-7-year olds. Resurgence may still occur if all children are antigen-negative, irrespective of the number tested. Mf-based criteria also show unfavourable results (PPV <95% or unpractically low threshold). CFA prevalences in the 5+ or 15+ population are the best predictors, and post-MDA threshold values for stopping MDA can be as high as 10% for 15+. These thresholds are robust for various alternative assumptions regarding baseline endemicity, biological parameters and sampling strategies.Conclusions/significanceFor African areas with moderate to high pre-treatment Mf prevalence that have had 6 or more rounds of annual ivermectin/albendazole MDA with adequate coverage, we recommend to adopt a CFA threshold prevalence of 10% in adults (15+) for stopping MDA. This could be combined with Mf testing of CFA positives to ensure absence of a significant Mf reservoir for transmission.
| S-EPMC9779720 | biostudies-literature
Project description:The Global Programme to Eliminate Lymphatic Filariasis was launched in 2000 to eliminate lymphatic filariasis (LF) as a public health problem by 1) interrupting transmission through mass drug administration (MDA) and 2) offering basic care to those suffering from lymphoedema or hydrocele due to the infection. Although impressive progress has been made, the initial target year of 2020 will not be met everywhere. The World Health Organization recently proposed 2030 as the new target year for elimination of lymphatic filariasis (LF) as a public health problem. In this letter, LF modelers of the Neglected Tropical Diseases (NTDs) Modelling Consortium reflect on the proposed targets for 2030 from a quantitative perspective. While elimination as a public health problem seems technically and operationally feasible, it is uncertain whether this will eventually also lead to complete elimination of transmission. The risk of resurgence needs to be mitigated by strong surveillance after stopping interventions and sometimes perhaps additional interventions.
| S-EPMC6833911 | biostudies-literature
Project description:BackgroundWith the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling.MethodsWe used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%.ResultsThree annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance).ConclusionsModeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.
| S-EPMC5982795 | biostudies-literature
Project description:In the global drive for elimination of lymphatic filariasis (LF), 15 countries have achieved validation of elimination as a public health problem (EPHP). Recent empirical evidence has demonstrated that EPHP does not always lead to elimination of transmission (EOT). Here we show how the probability of elimination explicitly depends on key biological parameters, many of which have been poorly characterized, leading to a poor evidence base for the elimination threshold. As more countries progress towards EPHP it is essential that this process is well-informed, as prematurely halting treatment and surveillance programs could pose a serious threat to global progress. We highlight that refinement of the weak empirical evidence base is vital to understand drivers of elimination and inform long-term policy.
| S-EPMC7413036 | biostudies-literature
Project description:BackgroundThe prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission.Methodology/principal findingWe present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997-2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6-7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts.ConclusionsWe conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF.
| S-EPMC4364952 | biostudies-literature
Project description:BackgroundThe current WHO-led initiative to eradicate the macroparasitic disease, lymphatic filariasis (LF), based on single-dose annual mass drug administration (MDA) represents one of the largest health programs devised to reduce the burden of tropical diseases. However, despite the advances made in instituting large-scale MDA programs in affected countries, a challenge to meeting the goal of global eradication is the heterogeneous transmission of LF across endemic regions, and the impact that such complexity may have on the effort required to interrupt transmission in all socioecological settings.MethodsHere, we apply a Bayesian computer simulation procedure to fit transmission models of LF to field data assembled from 18 sites across the major LF endemic regions of Africa, Asia and Papua New Guinea, reflecting different ecological and vector characteristics, to investigate the impacts and implications of transmission heterogeneity and complexity on filarial infection dynamics, system robustness and control.ResultsWe find firstly that LF elimination thresholds varied significantly between the 18 study communities owing to site variations in transmission and initial ecological parameters. We highlight how this variation in thresholds lead to the need for applying variable durations of interventions across endemic communities for achieving LF elimination; however, a major new result is the finding that filarial population responses to interventions ultimately reflect outcomes of interplays between dynamics and the biological architectures and processes that generate robustness/fragility trade-offs in parasite transmission. Intervention simulations carried out in this study further show how understanding these factors is also key to the design of options that would effectively eliminate LF from all settings. In this regard, we find how including vector control into MDA programs may not only offer a countermeasure that will reliably increase system fragility globally across all settings and hence provide a control option robust to differential locality-specific transmission dynamics, but by simultaneously reducing transmission regime variability also permit more reliable macroscopic predictions of intervention effects.ConclusionsOur results imply that a new approach, combining adaptive modelling of parasite transmission with the use of biological robustness as a design principle, is required if we are to both enhance understanding of complex parasitic infections and delineate options to facilitate their elimination effectively.
| S-EPMC4731922 | biostudies-literature
Project description:BackgroundLymphatic filariasis (LF) is a major public health problem in the Pacific Region, including in Fiji. Through transmission by the mosquito vector Aedes, Fiji has suffered the burden of remaining endemic with LF despite efforts at elimination prior to 1999. In the year 1999, Fiji agreed to take part in the Pacific Programme for Elimination of LF (PacELF) and the Global Programme to Eliminate LF.MethodsThis study reviewed and collated past data on LF in Fiji between 1997 and 2007. Sources included published papers as well as unpublished PacELF and WHO program meeting and survey reports. Records were held at Fiji's Department of Health and Medical Services, James Cook University and the WHO office in Suva, Fiji.ResultsBaseline surveys between 1997 and 2002 showed that Fiji was highly endemic for LF with an estimated 16.6% of the population antigen positive and 6.3% microfilaria positive at that time. Five rounds of annual mass drug administration (MDA) using albendazole and diethylcarbamazine commenced in 2002. Programmatic coverage reported was 58-70% per year, but an independent coverage survey in 2006 in Northern Division after the fifth MDA suggested that actual coverage may have been higher. Monitoring of the program consisted of antigen prevalence surveys in all ages with sentinel and spot check surveys carried out in 2002 (pre MDA), 2004, and 2005, together with knowledge, attitude, and practice surveys. The stop-MDA survey (C survey) in 2007 was a nationwide stratified cluster survey of all ages according to PacELF guidelines, designed to sample by administrative division to identify areas still needing MDA. The national antigen prevalence in 2007 was reduced by more than a third to 9.5%, ranging from 0.9% in Western Division to 15.4% in Eastern Division, while microfilaria prevalence was reduced by almost four-fifths to 1.4%. Having not reached the target threshold of 1% prevalence in all ages, Fiji wisely decided to continue MDA after 2007 but to move from nationwide implementation to four (later five) separate evaluation units with independent timelines using global guidelines, building on program experience to put more emphasis on increasing coverage through prioritized communication strategies, community participation, and morbidity alleviation.ConclusionFiji conducted nationwide MDA for LF annually between 2002 and 2006, monitored by extensive surveys of prevalence, knowledge, and coverage. From a high baseline prevalence in all divisions, large reductions in overall and age-specific prevalence were achieved, especially in the prevalence of microfilariae, but the threshold for stopping MDA was not reached. Fiji has a large rural and geographically widespread population, program management was not consistent over this period, and coverage achieved was likely not optimal in all areas. After learning from these many challenges and activities, Fiji was able to build on the progress achieved and the heterogeneity observed in prevalence to realign towards a more stratified and improved program after 2007. The information presented here will assist the country to progress towards validating elimination in subsequent years.
| S-EPMC7592542 | biostudies-literature
Project description:BackgroundLymphatic filariasis (LF) is targeted for elimination in Sierra Leone. Epidemiological coverage of mass drug administration (MDA) with ivermectin and albendazole had been reported >65% in all 12 districts annually. Eight districts qualified to implement transmission assessment survey (TAS) in 2013 but were deferred until 2017 due to the Ebola outbreak (2014-2016). In 2017, four districts qualified for conducting a repeat pre-TAS after completing three more rounds of MDA and the final two districts were also eligible to implement a pre-TAS.Methodology/principal findingsFor TAS, eight districts were surveyed as four evaluation units (EU). A school-based survey was conducted in children aged 6-7 years from 30 clusters per EU. For pre-TAS, one sentinel and one spot check site per district (with 2 spot check sites in Bombali) were selected and 300-350 persons aged 5 years and above were selected. For both surveys, finger prick blood samples were tested using the Filariasis Test Strips (FTS). For TAS, 7,143 children aged 6-7 years were surveyed across four EUs, and positives were found in three EUs, all below the critical cut-off value for each EU. For the repeat pre-TAS/pre-TAS, 3,994 persons over five years of age were surveyed. The Western Area Urban had FTS prevalence of 0.7% in two sites and qualified for TAS, while other five districts had sites with antigenemia prevalence >2%: 9.1-25.9% in Bombali, 7.5-19.4% in Koinadugu, 6.1-2.9% in Kailahun, 1.3-2.3% in Kenema and 1.7% - 3.7% in Western Area Rural.Conclusions/significanceEight districts in Sierra Leone have successfully passed TAS1 and stopped MDA, with one more district qualified for conducting TAS1, a significant progress towards LF elimination. However, great challenges exist in eliminating LF from the whole country with repeated failure of pre-TAS in border districts. Effort needs to be intensified to achieve LF elimination.
| S-EPMC7793261 | biostudies-literature