The Population Biology and Transmission Dynamics of Loa loa

Endemic to Central Africa, loiasis – or African eye worm (caused by the filarial nematode Loa loa) – affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions

Co-infection with Onchocerca volvulus and Loa loa microfilariae in central Cameroon: are these two species interacting?

Ivermectin treatment may induce severe adverse reactions in some individuals heavily infected with Loa loa. This hampers the implementation of mass ivermectin treatment against onchocerciasis in areas where Onchocerca volvulus and L. loa are co-endemic. In order to identify factors, including co-infections, which may explain the presence of high L. loa microfilaraemia in some individuals, we analysed data collected in 19 villages of central Cameroon. Two standardized skin snips and 30 mul of blood were obtained from each of 3190 participants and the microfilarial (mf) loads of both O. volvulus and L. loa were quantified. The data were analysed using multivariate hierarchical models. Individual-level variables were: age, sex, mf presence, and mf load; village-related variables included the endemicity levels for each infection. The two species show a certain degree of ecological separation in the study area. However, for a given individual host, the presence of microfilariae of one species was positively associated with the presence of microfilariae of the other (OR=1.79, 95% CI [1.43-2.24]). Among individuals harbouring Loa microfilariae, there was a slight positive relationship between the L. loa and O. volvulus mf loads which corresponded to an 11% increase in L. loa mf load per 100 O. volvulus microfilariae. Co-infection with O. volvulus is not sufficient to explain the very high L. loa mf loads harboured by some individuals

Density-dependent effects on the weight of female Ascaris lumbricoides infections of humans and its impact on patterns of egg production

<p>Abstract</p> <p>Background</p> <p><it>Ascaris lumbricoides </it>exhibits density-dependent egg production, a process which has a marked impact on both the transmission dynamics and the stability of the parasite population. Evidence suggests that the egg production of female <it>Ascaris </it>is also associated with the size of the worm. If worm size is mediated by density-dependent processes then the size of female worms may have a causal impact upon patterns of <it>Ascaris </it>egg production.</p> <p>Results</p> <p>We analyse data collected from a cohort of human hosts, and demonstrate that the per host mean weight (a proxy for size) of female <it>Ascaris </it>is dependent on the number of infecting females (worm burden) following a pattern of initial facilitation followed by limitation. Applying a negative binomial (NB) generalized linear model (GLM) and a zero-inflated negative binomial (ZINB) model we confirm that the per host female mean weight is significantly associated with per host egg production. Despite these associations, the mean weight of female <it>Ascaris </it>has little causal impact on patterns of density-dependent egg output. The ZINB model is able to account for the disproportionately large number of zero egg counts within the data and is shown to be a consistently better fit than the NB model. The probability of observing a zero egg count is demonstrated as being negatively associated with both female worm burden and female mean weight.</p> <p>Conclusion</p> <p>The mean weight of female <it>Ascaris </it>is statistically significantly associated with egg output, and follows a consistent pattern of facilitation preceding limitation with increasing female worm burden. Despite these relationships, incorporation of female <it>Ascaris </it>mean weight into models of egg output has little effect on patterns of density dependence. The ZINB model is a superior fit to the data than the NB model and provides additional information regarding the mechanisms that result in a zero egg count. The ZINB model is shown to be a useful tool for the analysis of individual-based egg output data.</p

Moxidectin: an oral treatment for human onchocerciasis

Moxidectin is a milbemycin endectocide recently approved for the treatment of human onchocerciasis. Onchocerciasis, earmarked for elimination of transmission, is a filarial infection endemic in Africa, Yemen, and the Amazonian focus straddling Venezuela and Brazil. Concerns over whether the predominant treatment strategy (yearly mass drug administration (MDA) of ivermectin) is sufficient to achieve elimination in all endemic foci have refocussed attention upon alternative treatments. Moxidectin’s stronger and longer microfilarial suppression compared to ivermectin in both phase II and III clinical trials indicates its potential as a novel powerful drug for onchocerciasis elimination

Introduction to the special issue: challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs

Twenty neglected tropical diseases (NTDs) are currently prioritised by the World Health Organization for eradication, elimination as a public health problem, elimination of transmission or control by 2030. This issue celebrates progress made since the 2012 London Declaration on NTDs and discusses challenges currently faced to achieve these goals. It comprises 14 contributions spanning NTDs tackled by intensified disease management to those addressed by preventive chemotherapy. Although COVID-19 negatively affected NTD programmes, it also served to spur new multisectoral approaches to strengthen school-based health systems. The issue highlights the needs to improve impact survey design, evaluate new diagnostics, understand the consequences of heterogeneous prevalence and human movement, the potential impact of alternative treatment strategies and the importance of zoonotic transmission. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'

Increased mortality attributed to Chagas disease: a systematic review and meta-analysis

Background: The clinical outcomes associated with Chagas disease remain poorly understood. In addition to the burden of morbidity, the burden of mortality due to Trypanosoma cruzi infection can be substantial, yet its quantification has eluded rigorous scrutiny. This is partly due to considerable heterogeneity between studies, which can influence the resulting estimates. There is a pressing need for accurate estimates of mortality due to Chagas disease that can be used to improve mathematical modelling, burden of disease evaluations, and cost-effectiveness studies. Methods: A systematic literature review was conducted to select observational studies comparing mortality in populations with and without a diagnosis of Chagas disease using the PubMed, MEDLINE, EMBASE, Web of Science and LILACS databases, without restrictions on language or date of publication. The primary outcome of interest was mortality (as all-cause mortality, sudden cardiac death, heart transplant or cardiovascular deaths). Data were analysed using a random-effects model to obtain the relative risk (RR) of mortality, the attributable risk percent (ARP), and the annual mortality rates (AMR). The statistic I-2 (proportion of variance in the meta-analysis due to study heterogeneity) was calculated. Sensitivity analyses and publication bias test were also conducted. Results: Twenty five studies were selected for quantitative analysis, providing data on 10,638 patients, 53,346 patient-years of follow-up, and 2739 events. Pooled estimates revealed that Chagas disease patients have significantly higher AMR compared with non-Chagas disease patients (0.18 versus 0.10; RR = 1.74, 95 % CI 1.49-2.03). Substantial heterogeneity was found among studies (I-2 = 67.3 %). The ARP above background mortality was 42.5 %. Through a sub-analysis patients were classified by clinical group (severe, moderate, asymptomatic). While RR did not differ significantly between clinical groups, important differences in AMR were found: AMR = 0.43 in Chagas vs. 0.29 in non-Chagas patients (RR = 1.40, 95 % CI 1.21-1.62) in the severe group; AMR = 0.16 (Chagas) vs. 0.08 (nonChagas) (RR = 2.10, 95 % CI 1.52-2.91) in the moderate group, and AMR = 0.02 vs. 0.01 (RR = 1.42, 95 % CI 1.14-1.77) in the asymptomatic group. Meta-regression showed no evidence of study-level covariates on the effect size. Publication bias was not statistically significant (Egger's test p=0.08). Conclusions: The results indicate a statistically significant excess of mortality due to Chagas disease that is shared among both symptomatic and asymptomatic populations

Modelling exposure heterogeneity and density dependence in onchocerciasis using a novel individual-based transmission model, EPIONCHO-IBM: implications for elimination and data needs

Background Density dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin. Methodology/Principal findings Density dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d’Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model. Conclusions/Significance This is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improving model predictions during MDA. We discuss possible ways in which such data may be collected as well as the importance of better understanding the effects of immunological responses on establishing parasites prior to and during ivermectin treatment

Required duration of mass ivermectin treatment for onchocerciasis elimination in Africa: a comparative modelling analysis.

BACKGROUND: The World Health Organization (WHO) has set ambitious targets for the elimination of onchocerciasis by 2020–2025 through mass ivermectin treatment. Two different mathematical models have assessed the feasibility of reaching this goal for different settings and treatment scenarios, namely the individual-based microsimulation model ONCHOSIM and the population-based deterministic model EPIONCHO. In this study, we harmonize some crucial assumptions and compare model predictions on common outputs. METHODS: Using a range of initial endemicity levels and treatment scenarios, we compared the models with respect to the following outcomes: 1) model-predicted trends in microfilarial (mf) prevalence and mean mf intensity during 25 years of (annual or biannual) mass ivermectin treatment; 2) treatment duration needed to bring mf prevalence below a provisional operational threshold for treatment interruption (pOTTIS, i.e. 1.4 %), and 3) treatment duration needed to drive the parasite population to local elimination, even in the absence of further interventions. Local elimination was judged by stochastic fade-out in ONCHOSIM and by reaching transmission breakpoints in EPIONCHO. RESULTS: ONCHOSIM and EPIONCHO both predicted that in mesoendemic areas the pOTTIS can be reached with annual treatment, but that this strategy may be insufficient in very highly hyperendemic areas or would require prolonged continuation of treatment. For the lower endemicity levels explored, ONCHOSIM predicted that the time needed to reach the pOTTIS is longer than that needed to drive the parasite population to elimination, whereas for the higher endemicity levels the opposite was true. In EPIONCHO, the pOTTIS was reached consistently sooner than the breakpoint. CONCLUSIONS: The operational thresholds proposed by APOC may have to be adjusted to adequately reflect differences in pre-control endemicities. Further comparative modelling work will be conducted to better understand the main causes of differences in model-predicted trends. This is a pre-requisite for guiding elimination programmes in Africa and refining operational criteria for stopping mass treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1159-9) contains supplementary material, which is available to authorized users

Loa loa: More Than Meets the Eye?

Filarial nematodes cause neglected tropical diseases (NTDs) such as river blindness, elephantiasis, and African eye worm. Global control and elimination efforts are well underway for the former two, and epidemiological models have played a crucial role in understanding the impact of interventions and guiding control policy. However, for the latter (caused by Loa loa), there are no specific transmission models, and the disease has not been included among the prioritized NTDs. Maria-Gloria Basanez and her Helminth Ecology Research Group at Imperial College London work collaboratively on developing mathematical models for human and zoonotic helminthiases and other vector-borne NTDs. In this interview, the authors shared with Trends in Parasitology why loiasis may be more than meets the eye and how modelling can best be leveraged to help control human filarial infections