Non-local validated parametrization of an agent-based model of local-scale Taenia solium transmission in North-West Peru.

The pork tapeworm, Taenia solium, is the cause of a preventable zoonotic disease, cysticercosis, affecting both pigs and humans. Continued endemic transmission of T. solium is a major contributor of epilepsy and other neurologic morbidity, and the source of important economic losses, in many rural areas of developing countries. Simulation modelling can play an important role in aiding the design and evaluation of strategies to control or even eliminate transmission of the parasite. In this paper, we present a new agent based model of local-scale T. solium transmission and a new, non-local, approach to the model calibration to fit model outputs to observed human taeniasis and pig cysticercosis prevalence simultaneously for several endemic villages. The model fully describes all relevant aspects of T. solium transmission, including the processes of pig and human infection, the spatial distribution of human and pig populations, the production of pork for human consumption, and the movement of humans and pigs in and out in several endemic villages of the northwest of Peru. Despite the high level of uncertainty associated with the empirical measurements of epidemiological data associated with T. solium, the non-local calibrated model parametrization reproduces the observed prevalences with an acceptable precision. It does so not only for the villages used to calibrate the model, but also for villages not included in the calibration process. This important finding demonstrates that the model, including its calibrated parametrization, can be successfully transferred within an endemic region. This will enable future studies to inform the design and optimization of T. solium control interventions in villages where the calibration may be prevented by the limited amount of empirical data, expanding the possible applications to a wider range of settings compared to previous models

Chagas Cardiomyopathy in the Context of the Chronic Disease Transition

Latin America is undergoing a transition from disease patterns characteristic of developing countries with high rates of infectious disease and premature deaths to a pattern more like industrialized countries, in which chronic conditions such as obesity, hypertension and diabetes are more common. Many rural residents with Chagas disease have now migrated to cities, taken on new habits and may suffer from both types of disease. We studied heart disease among 394 adults seen by cardiologists in a public hospital in the city of Santa Cruz, Bolivia; 64% were infected with T. cruzi, the parasite that causes Chagas disease. Both T. cruzi infected and uninfected patients had a high rate of hypertension (64%) and overweight (67%), with no difference by infection status. Nearly 60% of symptomatic congestive heart failure was due to Chagas disease; mortality was also higher for infected than uninfected patients. Males and older patients had more severe Chagas heart disease. Chagas heart disease remains an important cause of congestive heart failure in this hospital population, but often occurs in patients who also have obesity, hypertension and/or other cardiac risk factors

Laboratory Diagnosis of Neurocysticercosis (\u3ci\u3eTaenia solium\u3c/i\u3e)

Neurocysticercosis accounts for approximately 30% of all epilepsy cases in most developing countries. The immunodiagnosis of cysticercosis is complex and strongly influenced by the course of infection, the disease burden, the cyst location, and the immune response of the host. The main approach to immunodiagnosis should thus be to evaluate whether the serological results are consistent with the diagnosis suggested by imaging. Antibody detection is performed using lentil lectin-purified parasite antigens in an enzyme-linked immunoelectrotransfer blot format, while antigen detection uses a monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Promising new assay configurations have been developed for the detection of both antibody and antigen, including assays based on synthetic or recombinant antigens that may reduce costs and improve assay reproducibility and multiplex bead-based assays that may provide simultaneous quantitative results for several target antigens or antibodies

The data are inadequate to assess safety and efficacy of mass chemotherapy for Taenia solium taeniasis.

As members of the Pan American Health Organization (PAHO) and World Health Organization (WHO) guidelines development group on chemotherapy strategies for the control of Taenia solium taeniasis, we are very disappointed at the systematic review by Haby and colleagues. With respect to the analysis of efficacy, the authors did not account for differences in the methods used to ascertain the outcome in the studies analyzed. There are also major concerns regarding the safety analyses. Few of the included studies used carefully designed active surveillance protocols to detect epileptic seizures and/or chronic progressive headaches. These neurologic side effects, due the inadvertent killing of viable brain cysts, have been noted after mass therapy with praziquantel and albendazole. We wholeheartedly agree with the authors' statement in their discussion that control programs applying chemotherapy using mass drug administration "need to be informed by evidence of the best drug and dose in terms of efficacy and side-effects." Unfortunately, the flawed analysis that was published is contrary to that goal

GPS tracking of free-range pigs in rural communities in Zambia : an explorative study towards future ring treatment strategies for Taenia solium

Background: Although elimination of T. solium is achievable using mass drug administration programmes, more sustainable strategies to control the disease are urgently needed. As such, 100-m ring treatments have been shown effective in Peru, though results might not be directly generalizable to sub-Saharan settings. Pig movements play a vital role in the transmission and consequently the success of ring treatment programmes towards T. solium. Objectives: Our study aimed to explore roaming patterns of pigs in T. solium endemic communities in Zambia, particularly focusing on the time spent and the number of recurrences outside different circles around the pigs’ household. Material and methods: Global Positioning System (GPS) technology was used to track 48 free roaming pigs in two rural neighbourhoods in Eastern Province of Zambia. Tracking of pigs took place during April 2019 (end of the rainy season) and October 2019 (end of the dry season). The number of revisitations and the time spent outside a ring around the household of the pig were calculated for circles of different radii (50m, 100m, and 250m) around the coordinate of the pigs’ household. Results: The tracking time of 43 pigs in the final analysis set ranged between 44 and 95 hours. Pigs spent a median of 13% of the tracked time outside the 100-m radius, ranging between pigs from 0% to 91%. The median number of visits per day outside this ring was 6. Overall, 25 pigs (58%) went at least once outside the 250-m ring. The odds of traveling outside the 250-m radius was estimated to be 4 (95% CI 1-16) times higher in the dry season compared to the rainy season. Conclusion: The vast majority of pigs spent most of their time within a 100-m circle around their household, supporting the use of 100-m ring treatments. Nevertheless, further studies are required to investigate the importance of the time spent outside the 100-m ring, as well as the open defecation behaviour of people

Feasibility of a point-of-care test based on quantum dots with a mobile phone reader for detection of antibody responses.

We developed a novel and portable fluorescent sensor that integrates a lateral flow assay with a quantum dot (Qdots) label and a mobile phone reader for detection of specific antibodies in human serum. We evaluated the utility of this assay to test for antibodies to the Taenia solium rT24H antigen. It was a retrospective study by examining 112 positive human sera from patients with neurocysticercosis (NCC) including samples from patients with single viable cyst (n = 18), two or more viable cysts (n = 71), and subarachnoid (racemose) cysts (n = 23). These samples were collected from previous study subjects in Lima, Peru under an approved study protocol in Peru. The sera were made anonymous under a protocol approved by the CDC Institutional Review Board. Definitive diagnosis of the subject was established by computed-tomography and/or magnetic resonance imaging. To test the specificity of the assay, we evaluated a panel of serum samples obtained from patients with other infections (n = 24), and serum samples from persons in the United States and Egypt who had not traveled outside their country, and therefore are presumed negative for cysticercosis (n = 128). The assay specificity in the negative panel was 99% (95-100%) while assay sensitivity was 89% (79-95%) in NCC patients with two or more viable cysts. Our assay has performance characteristics similar to those of traditional platforms for the detection of NCC and shows promise as a mobile phone reader-based point-of-care test for antibody detection

GPS Tracking of Free-Ranging Pigs to Evaluate Ring Strategies for the Control of Cysticercosis/Taeniasis in Peru

<div><p>Background</p><p><i>Taenia solium</i>, a parasitic cestode that affects humans and pigs, is the leading cause of preventable epilepsy in the developing world. <i>T</i>. <i>solium</i> eggs are released into the environment through the stool of humans infected with an adult intestinal tapeworm (a condition called taeniasis), and cause cysticercosis when ingested by pigs or other humans. A control strategy to intervene within high-risk foci in endemic communities has been proposed as an alternative to mass antihelminthic treatment. In this ring strategy, antihelminthic treatment is targeted to humans and pigs residing within a 100 meter radius of a pig heavily-infected with cysticercosis. Our aim was to describe the roaming ranges of pigs in this region, and to evaluate whether the 100 meter radius rings encompass areas where risk factors for <i>T</i>. <i>solium</i> transmission, such as open human defecation and dense pig activity, are concentrated.</p><p>Methodology/Principal Findings</p><p>In this study, we used Global Positioning System (GPS) devices to track pig roaming ranges in two rural villages of northern Peru. We selected 41 pigs from two villages to participate in a 48-hour tracking period. Additionally, we surveyed all households to record the locations of open human defecation areas. We found that pigs spent a median of 82.8% (IQR: 73.5, 94.4) of their time roaming within 100 meters of their homes. The size of home ranges varied significantly by pig age, and 93% of the total time spent interacting with open human defecation areas occurred within 100 meters of pig residences.</p><p>Conclusions/Significance</p><p>These results indicate that 100 meter radius rings around heavily-infected pigs adequately capture the average pig’s roaming area (i.e., home range) and represent an area where the great majority of exposure to human feces occurs.</p></div

Ring-screening to control endemic transmission of Taenia solium.

BACKGROUND:Taenia solium is a major cause of preventable epilepsy in developing nations. Screening and treatment of human intestinal stage infection (taeniasis) within high-risk foci may reduce transmission and prevent epilepsy by limiting human exposure to infective eggs. We piloted a ring-strategy that involves screening and treatment for taeniasis among households located nearby pigs heavily-infected with the larval stage (cysticercosis). These pigs mark areas of increased transmission and can be identified by tongue examination. METHODOLOGY:We selected two villages in northern Peru for a controlled prospective interventional cohort pilot study. In the intervention village (1,058 residents) we examined the tongues of all pigs every 4 months for nodules characteristic of cysticercosis. We then screened all residents living within 100-meters of any tongue-positive pig using enzyme-linked immunosorbent assay to detect Taenia antigens in stool. Residents with taeniasis were treated with niclosamide. In both the intervention and control (753 residents) we measured incidence of exposure by sampling the pig population every 4 months for serum antibodies against cysticercosis using enzyme-linked immunoelectrotransfer blot. PRINCIPAL FINDINGS:Baseline seroincidence among pigs born during the study was 22.6 cases per 100 pigs per-month (95% confidence interval [CI] 17.0-30.0) in the intervention and 18.1 (95% CI 12.7-25.9) in the control. After one year we observed a 41% reduction in seroincidence in the intervention village compared to baseline (incidence rate ratio 0.59, 95% CI 0.41-0.87) while the seroincidence in the control village remained unchanged. At study end, the prevalence of taeniasis was nearly 4 times lower in the intervention than in the control (prevalence ratio 0.28, 95% CI 0.08-0.91). CONCLUSIONS/SIGNIFICANCE:Ring-screening reduced transmission of T. solium in this pilot study and may provide an effective and practical approach for regions where resources are limited. However, this strategy requires validation in larger populations over a greater period of time

CystiHuman: A model of human neurocysticercosis.

INTRODUCTION: The Taenia solium tapeworm is responsible for cysticercosis, a neglected tropical disease presenting as larvae in the body of a host following taenia egg ingestion. Neurocysticercosis (NCC), the name of the disease when it affects the human central nervous system, is a major cause of epilepsy in developing countries, and can also cause intracranial hypertension, hydrocephalus and death. Simulation models can help identify the most cost-effective interventions before their implementation. Modelling NCC should enable the comparison of a broad range of interventions, from treatment of human taeniasis (presence of an adult taenia worm in the human intestine) to NCC mitigation. It also allows a focus on the actual impact of the disease, rather than using proxies as is the case for other models. METHODS: This agent-based model is the first model that simulates human NCC and associated pathologies. It uses the output of another model, CystiAgent, which simulates the evolution of pig cysticercosis and human taeniasis, adding human and cyst agents, including a model of cyst location and stage, human symptoms, and treatment. CystiHuman also accounts for delays in the appearance of NCC-related symptoms. It comprises three modules detailing cyst development, seizure probability and timing, and intracranial hypertension/hydrocephalus, respectively. It has been implemented in Java MASON and calibrated in three endemic villages in Peru, then applied to another village (Rica Playa) to compare simulation results with field data in that village. RESULTS AND DISCUSSION: Despite limitations in available field data, parameter values found through calibration are plausible and simulated outcomes in Rica Playa are close to actual values for NCC prevalence and the way it increases with age and cases with single lesions. Initial simulations further suggest that short-term interventions followed by a rapid increase in taeniasis prevalence back to original levels may have limited impacts on NCC prevalence