Development and Laboratory Evaluation of a Simple, Field-Applicable Coproantigen Enzyme-Linked Immunosorbent Assay for Diagnosis of Taeniasis in Northern Peru.

Coproantigen detection by enzyme-linked immunosorbent assay (coAg ELISA) is a vital tool for detecting and treating cases of Taenia solium taeniasis. However, the assay's procedures require costly materials and sophisticated equipment, which are typically inaccessible in rural settings where the disease is endemic. To overcome these barriers, we developed and evaluated a field-applicable coAg ELISA. The field coAg ELISA was developed and evaluated across four phases using known positive and negative stool samples collected from northern Peru. Phase I focused on field assay development, phase II on a small-scale performance evaluation, phase III on a large-scale evaluation, and phase IV on the use and reliability of a colorimetric scale card. All samples were processed using the field and standard assay procedures and compared using signal-to-noise ratios, correlation tests, performance characteristics, and agreement statistics where appropriate. The field coAg ELISA using reagents stored at -20°C and commercially available water and milk powder, and relying on spontaneous separation of the supernatant, had performance comparable to the standard assay. The field coAg ELISA was strongly correlated with the standard in both the small- and large-scale laboratory evaluation (r = 0.99 and r = 0.98, respectively). Finally, the field assay had an almost perfect agreement between independent readers (kappa = 0.975) and between each reader and the spectrophotometer. The field coAg ELISA demonstrated performance comparable to the standard, providing a low-cost alternative to the standard assay for identifying cases of intestinal taeniasis in a low-resource setting.

Evaluating the Role of Corrals and Insects in the Transmission of Porcine Cysticercosis: A Cohort Study.

The widespread dispersion of pigs infected with cysticercosis across endemic villages, low cyst burden among infected pigs, and low prevalence of taeniasis all suggest that pig ingestion of human feces is not the only mode of transmission for Taenia solium. Our objective was to evaluate the risk of porcine cysticercosis associated with exposure to human feces, dung beetles, and flies in an endemic community setting. We used a cluster-randomized cohort design to compare the risk of developing antibodies and infection among 120 piglets raised in either free-roaming (FR), standard corral (SC), or netted corral environments (NC). We collected monthly blood samples to detect serum antibodies and necropsied all pigs after 10 months to identify cysts. A total of 66 piglets developed antibodies with the relative risk of seropositivity in FR vs. all corralled pigs increasing significantly after 18 weeks. Of 108 necropsied pigs, 15 had T. solium cysts, all belonging to the FR group. Corrals were protective against infection but less so against seropositivity. NC, which did not completely exclude insects, did not provide added protection against seropositivity as compared to SC. The results of this study suggest that dung beetles and flies do not play an important role in infection.

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.

Geographically Targeted Interventions versus Mass Drug Administration to Control Taenia solium Cysticercosis, Peru.

Optimal control strategies for Taenia solium taeniasis and cysticercosis have not been determined. We conducted a 2-year cluster randomized trial in Peru by assigning 23 villages to 1 of 3 geographically targeted intervention approaches. For ring screening (RS), participants living near pigs with cysticercosis were screened for taeniasis; identified cases were treated with niclosamide. In ring treatment (RT), participants living near pigs with cysticercosis received presumptive treatment with niclosamide. In mass treatment (MT), participants received niclosamide treatment every 6 months regardless of location. In each approach, half the villages received targeted or mass oxfendazole for pigs (6 total study arms). We noted significant reductions in seroincidence among pigs in all approaches (67.1% decrease in RS, 69.3% in RT, 64.7% in MT; p<0.001), despite a smaller proportion of population treated by targeted approaches (RS 1.4%, RT 19.3%, MT 88.5%). Our findings suggest multiple approaches can achieve rapid control of T. solium transmission.

Population Screening for Urine Antigens to Detect Asymptomatic Subarachnoid Neurocysticercosis: A Pilot Study in Northern Peru.

Subarachnoid neurocysticercosis (SANCC) is a severe and progressive brain infection with Taenia solium. We performed a pilot study of noninvasive screening for SANCC in two endemic villages in northern Peru using a urine antigen screen followed by brain magnetic resonance imaging for participants with elevated levels of antigen. Among the 978 participants screened, we identified eight individuals with SANCC, many of whom were asymptomatic. This represents a minimum prevalence of 0.8% of SANCC, a level higher than expected based on prior studies, and a positive predictive value of 62% for our novel urine screening test. Future studies should confirm whether early detection and management improve clinical outcomes.

Seasonal patterns in risk factors for Taenia solium transmission: a GPS tracking study of pigs and open human defecation in northern Peru.

BACKGROUND: Taenia solium (cysticercosis) is a parasitic cestode that is endemic in rural populations where open defecation is common and free-roaming pigs have access to human feces. The purpose of this study was to examine the roaming patterns of free-range pigs, and identify areas where T. solium transmission could occur via contact with human feces. We did this by using GPS trackers to log the movement of 108 pigs in three villages of northern Peru. Pigs were tracked for approximately six days each and tracking was repeated in the rainy and dry seasons. Maps of pig ranges were analyzed for size, distance from home, land type and contact with human defecation sites, which were assessed in a community-wide defecation survey. RESULTS: Consistent with prior GPS studies and spatial analyses, we found that the majority of pigs remained close to home during the tracking period and had contact with human feces in their home areas: pigs spent a median of 79% (IQR: 61-90%) of their active roaming time within 50 m of their homes and a median of 60% of their contact with open defecation within 100 m of home. Extended away-from-home roaming was predominately observed during the rainy season; overall, home range areas were 61% larger during the rainy season compared to the dry season (95% CI: 41-73%). Both home range size and contact with open defecation sites showed substantial variation between villages, and contact with open defecation sites was more frequent among pigs with larger home ranges and pigs living in higher density areas of their village. CONCLUSIONS: Our study builds upon prior work showing that pigs predominately roam and have contact with human feces within 50-100 m of the home, and that T. solium transmission is most likely to occur in these concentrated areas of contact. This finding, therefore, supports control strategies that target treatment resources to these areas of increased transmission. Our finding of a seasonal trend in roaming ranges may be useful for control programs relying on pig interventions, and in the field of transmission modeling, which require precise estimates of pig behavior and risk.

To Really Know the Disease: Creating a Participatory Community Education Workshop about Taenia solium Focused on Physical, Economic, and Epidemiologic Evidence.

Cysticercosis, caused by Taenia solium, is a neglected disease that causes preventable epilepsy. We conducted an experiential learning workshop in northern Peru to educate community members on T. solium transmission and motivate participation in community-led prevention and control. The workshop included presentation of local economic and epidemiologic data, followed by hands-on participation in pig dissection, group discussion of the T. solium life cycle, and viewing of eggs and nascent tapeworms with light microscopes. Among heads of household, we used community survey data to compare knowledge of the three-stage parasite life cycle at baseline and 2 months postworkshop. Knowledge of the life cycle increased significantly after the workshop, with greater gains for workshop attendees than non-attendees. Prior knowledge and workshop attendance were significant predictors of postworkshop knowledge. The use of local evidence and experiential learning positively affected knowledge of T. solium transmission, laying the foundation for subsequent community-engaged control efforts.

Evaluating Urban Taeniasis as a Threat to Cysticercosis Elimination in Northern Peru.

Reintroduction of Taenia solium into a region in Peru where it had been eliminated prompted evaluation of the possibility of reintroduction from an urban reservoir of taeniasis. In a cross-sectional study of an adjacent urban area, we found low prevalence of taeniasis (4/1,621; 0.25%), suggesting minimal risk of parasite reintroduction into rural areas through this route.

Barriers to Participation in a Community-Based Program to Control Transmission of Taenia solium in Peru.

Infection of the brain with Taenia solium larvae (neurocysticercosis) is a leading cause of preventable epilepsy worldwide. Effective and sustainable strategies to control parasite transmission in rural endemic communities are needed to prevent the disease. Surveillance and targeted intervention around infected pigs (ring control strategy) have been shown to be effective when carried out by research teams. However, this strategy has not been implemented or tested as a community-based program. In this small trial in northern Peru, eight villages were randomly assigned to community-led surveillance and treatment (five villages, 997 residents) or control (three villages, 1,192 residents). In intervention villages, community-led surveillance and reporting were promoted by community health workers, radio advertisement, and school and household education. Each suspected pig infection was verified, with confirmed cases resulting in treatment with niclosamide for taeniasis and oxfendazole for pigs in clusters of homes nearby. No incentives beyond human and pig treatment were offered. Control villages received basic disease education but no treatment intervention in response to reports. Despite 14 case reports, community-based replication of ring control strategy did not replicate prior results. After 12 months, there was no change in seroincidence in intervention villages between the baseline and study end, and no difference compared with control villages. There was no difference in prevalence of taeniasis or porcine cysticercosis at study end. Community members described lack of knowledge as the main reason for not reporting infected pigs. Further exploration of methods to transfer ring strategy and other control interventions for cysticercosis to the community is needed.

High Prevalence of Asymptomatic Neurocysticercosis in an Endemic Rural Community in Peru.

BACKGROUND: Neurocysticercosis is a common helminthic infection of the central nervous system and an important cause of adult-onset epilepsy in endemic countries. However, few studies have examined associations between neurologic symptoms, serology and radiographic findings on a community-level. METHODOLOGY: We conducted a population-based study of resident's ≥2 years old in a highly endemic village in Peru (pop. 454). We applied a 14 -question neurologic screening tool and evaluated serum for antibodies against Taenia solium cysticercosis using enzyme-linked immunoelectrotransfer blot (LLGP-EITB). We invited all residents ≥18 years old to have non-contrast computerized tomography (CT) of the head. PRINCIPAL FINDINGS: Of the 385 residents who provided serum samples, 142 (36.9%) were seropositive. Of the 256 residents who underwent CT scan, 48 (18.8%) had brain calcifications consistent with NCC; 8/48 (17.0%) reported a history of headache and/or seizures. Exposure to T. solium is very common in this endemic community where 1 out of 5 residents had brain calcifications. However, the vast majority of people with calcifications were asymptomatic. CONCLUSION: This study reports a high prevalence of NCC infection in an endemic community in Peru and confirms that a large proportion of apparently asymptomatic residents have brain calcifications that could provoke seizures in the future.