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

Single Spin Asymmetry Parameter from Deeply Virtual Compton Scattering of Hadrons up to Twist-3 accuracy: I. Pion case

The study of deeply virtual Compton scattering has shown that electromagnetic gauge invariance requires, to leading order, not only twist two but additional twist three contributions. We apply this analysis and, using the Ellis-Furmanski-Petronzio factorization scheme, compute the single (electron) spin asymmetry arising in the collision of longitudinally polarized electrons with hadrons up to twist 3 accuracy. In order to simplify the kinematics we restrict the actual calculation to pions in the chiral limit. The process is described in terms of the generalized parton distribution functions which we obtain within a bag model framework.Comment: 18 pages, Late

The Big Pet Diabetes Survey: Perceived Frequency and Triggers for Euthanasia

Current pet diabetes mellitus (DM) treatment necessitates the active daily involvement of owners and can be costly. The current study aimed to investigate the owner population which opts for euthanasia instead of DM treatment. A survey was designed using multiple feedback steps and made available online to veterinarians world-wide. A total of 1192 veterinarians completed the survey and suggested a median one in 10 diabetic pets are euthanased at diagnosis; a further median one in 10 within one year because of lack of success or compliance. Perceived most important motivating factors included “presence concurrent disease” (45% respondents); “costs” (44%); “animal age” (37%); “problems obtaining adequate control” (35%); “pet welfare” (35%); and “impact owner’s lifestyle” (32%). Cats in Canadian (odds ratio (OR) 2.7), Australian (OR 2.3), rural (OR 1.6) and mixed (OR 1.7) practices were more likely to be euthanased because of DM diagnosis, while cats presented to referral/university were less likely to be euthanased (OR 0.6). Dogs were more likely to be euthanased because of DM in Canadian (OR 1.8), rural (OR 1.8) and mixed (OR 1.6) practices. The survey results suggest that benefit exists in improved DM education with emphasis on offering a choice of treatment styles ranging from intense and expensive to hands-off and cheap

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

Results from 2 cohort studies in central Africa show that clearance of Wuchereria bancrofti infection after repeated rounds of mass drug administration with albendazole alone is closely linked to individual adherence

BACKGROUND: Two community trials conducted from 2012 to 2018 in the Republic of Congo and the Democratic Republic of the Congo demonstrated the efficacy of semiannual mass drug administration (MDA) with albendazole (ALB) alone on lymphatic filariasis (LF). However, a high interindividual heterogeneity in the clearance of infection was observed. METHODS: We analyzed trial data to assess the effect of individual adherence to ALB MDA on clearance of circulating filarial antigenemia (CFA) and microfilaremia. Community residents were offered a single dose of ALB every 6 months and tested for LF with a rapid test for CFA at baseline and then annually. CFA test results were scored on a semiquantitative scale. At each round, microfilaremia was assessed in CFA-positive individuals. All CFA-positive individuals for whom at least 1 follow-up measure was available were included in the analyses. Parametric survival models were used to assess the influence of treatment adherence on LF infection indicators. RESULTS: Of 2658 individuals enrolled in the trials, 394 and 129 were eligible for analysis of CFA and microfilaremia clearance, respectively. After adjusting for age, sex, and initial CFA score, the predicted mean time for clearing CFA was shorter in persons who had taken 2 doses of ALB per year (3.9 years) than in persons who had taken 1 or 0 dose (4.4 and 5.3 years; P \u3c .001 for both). A similar pattern was observed for microfilaremia clearance. CONCLUSIONS: These results demonstrate a clear dose-response relationship for the effect of ALB on clearance of CFA and microfilaremia

Epilepsy in Onchocerciasis Endemic Areas: Systematic Review and Meta-analysis of Population-Based Surveys

Epilepsy is particularly common in tropical areas. One main reason is that many endemic infections have neurological consequences. In addition, the medical, social and demographic burden of epilepsy remains substantial in these countries where it is often seen as a contagious condition and where the aetiology is often undetermined. For several decades, field researchers had reported some overlapping between the geographical distributions of epilepsy and onchocerciasis, a parasitic disease caused by the filarial worm Onchocerca volvulus which afflicts some 40 million persons worldwide. Here, we conducted a statistical analysis of all the data available on the relationship between the two conditions to determine whether the proportion of people suffering from epilepsy in a community could be related to the frequency of onchocerciasis. The combined results of the eight studies carried out in west, central and east Africa indicate a close epidemiological association between the two diseases. Should a causative relationship be demonstrated, onchocerciasis, which is known as “river blindness” because of its most serious sequela and the distribution of its vectors, could thus also be called “river epilepsy”. More research is needed to determine the mechanisms explaining this association and to assess the burden of onchocerciasis-associated epilepsy

Projected Number of People With Onchocerciasis-Loiasis Coinfection in Africa, 1995 to 2025

BACKGROUND: Onchocerciasis elimination through mass drug administration (MDA) is hampered by coendemicity of Loa loa, as people with high L. loa microfilariae (mf) density can develop serious adverse events (SAEs) after ivermectin treatment. We assessed the geographical overlap of onchocerciasis and loiasis prevalence and estimated the number of coinfected individuals at risk of post-ivermectin SAEs in West and Central Africa from 1995 to 2025. METHODS: Focusing on regions with suspected loiasis transmission in 14 countries, we overlaid precontrol maps of loiasis and onchocerciasis prevalence to calculate precontrol prevalence of coinfection by 5 km2 × 5 km2 pixel, distinguishing different categories of L. loa mf intensity. Using statistical and mathematical models, we predicted prevalence of both infections and coinfection for 2015 and 2025, accounting for the impact of MDA with ivermectin. RESULTS: The number of people infected with onchocerciasis was predicted to decline from almost 19 million in 1995 to 4 million in 2025. Of these, 137 000 people were estimated to also have L. loa hypermicrofilaremia (≥20 000 L. loa mf/mL) in 1995, declining to 31 000 in 2025. In 2025, 92.8% of coinfecte

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

Implementation of the Diagnostic Pathfinder, an Internet-Based Tool to Teach Clinical Pathology in Diverse Educational Settings

Those of us who teach clinical pathology to veterinary students are continually exploring more effective ways to help students master the application of laboratory medicine to the solution of clinical problems. We not only must teach students the pathophysiologic basis of disease as applied to clinical laboratory data, but we also must instill a diagnostic reasoning process that is consistent and reliable. This reasoning process must be successful when applied to both common and uncommon diseases in multiple species, and also must be suitable for characterizing emerging diseases. Many of us have successfully used mechanism-based instruction to teach diagnostic reasoning, rather than presenting lists of facts and relying upon students to rote memorize