Seth E. O'Neal

Neurocysticercosis: Neglected but Not Forgotten

Neurocysticercosis (NCC) is an infection of the central nervous system caused by the larval form of the tapeworm Taenia solium. Infections occur following the accidental ingestion of tapeworm ova found in human feces. NCC is a major cause of epilepsy and disability in many of the worlds poorer countries where families raise free-roaming pigs that are able to ingest human feces. It is frequently diagnosed in immigrant populations in the United States and Canada, reflecting the high endemicity of the infection in their countries of origin [1]. Although parenchymal cysts are the most common location in the brain and cause seizures, cysts may also be present in the ventricles, meninges, spinal cord, eye, and subarachnoid spaces. Involvement in these other sites may result in aberrant growth (racemose cysts) and complicated disease that is difficult to treat and may cause increased morbidity and mortality.

Hospitalization Frequency and Charges for Neurocysticercosis, United States, 2003-2012

Total hospital charges exceeded US

Chagas Cardiomyopathy in the Context of the Chronic Disease Transition

900 million, and nearly three-quarters of hospitalized patients were Hispanic.

Seroprevalence of antibodies against Taenia solium cysticerci among refugees resettled in United States

Background Patients with Chagas disease have migrated to cities, where obesity, hypertension and other cardiac risk factors are common. Methodology/Principal Findings The study included adult patients evaluated by the cardiology service in a public hospital in Santa Cruz, Bolivia. Data included risk factors for T. cruzi infection, medical history, physical examination, electrocardiogram, echocardiogram, and contact 9 months after initial data collection to ascertain mortality. Serology and PCR for Trypanosoma cruzi were performed. Of 394 participants, 251 (64%) had confirmed T. cruzi infection by serology. Among seropositive participants, 109 (43%) had positive results by conventional PCR; of these, 89 (82%) also had positive results by real time PCR. There was a high prevalence of hypertension (64%) and overweight (body mass index [BMI] >25; 67%), with no difference by T. cruzi infection status. Nearly 60% of symptomatic congestive heart failure was attributed to Chagas cardiomyopathy; mortality was also higher for seropositive than seronegative patients (p = 0.05). In multivariable models, longer residence in an endemic province, residence in a rural area and poor housing conditions were associated with T. cruzi infection. Male sex, increasing age and poor housing were independent predictors of Chagas cardiomyopathy severity. Males and participants with BMI ≤25 had significantly higher likelihood of positive PCR results compared to females or overweight participants. Conclusions Chagas cardiomyopathy remains an important cause of congestive heart failure in this hospital population, and should be evaluated in the context of the epidemiological transition that has increased risk of obesity, hypertension and chronic cardiovascular disease.

Geographic Correlation between Tapeworm Carriers and Heavily Infected Cysticercotic Pigs

Cysticercosis is an infection caused by a pork tapeworm that creates cysts in different areas of the human body. Sometimes, these parasites can get into the infected patient’s brain and lead to epilepsy or other neurologic disorders. Cysticercosis is most common in developing countries that have poor sanitation and where pigs feed on human waste; however, cases in the United States are increasing. A recent study found that many refugees who settle in the United States, including those from Burma, Laos, Burundi, and Bhutan, have been infected with the tapeworm. The occurrence of cysticercosis among these groups has clinical and public health implications because US physicians might not be familiar with this disease and its symptoms. Cysticercosis should be suspected in refugees who have seizures, headache, or other unexplained neurologic symptoms. Physicians should also be aware that treatment for intestinal parasites, routinely given to refugees before they leave their homeland, can cause serious neurologic reactions in those already infected with the tapeworm.

Ring-Screening to Control Endemic Transmission of Taenia solium

Background Neurocysticercosis is a leading cause of preventable epilepsy in the developing world. Sustainable community-based interventions are urgently needed to control transmission of the causative parasite, Taenia solium. We examined the geospatial relationship between live pigs with visible cysticercotic cysts on their tongues and humans with adult intestinal tapeworm infection (taeniasis) in a rural village in northern Peru. The objective was to determine whether tongue-positive pigs could indicate high-risk geographic foci for taeniasis to guide targeted screening efforts. This approach could offer significant benefit compared to mass intervention. Methods We recorded geographic coordinates of all village houses, collected stool samples from all consenting villagers, and collected blood and examined tongues of all village pigs. Stool samples were processed by enzyme-linked immunosorbent assay (ELISA) for presence of Taenia sp. coproantigens indicative of active taeniasis; serum was processed by enzyme-linked immunoelectrotransfer blot for antibodies against T. solium cysticercosis (EITB LLGP) and T. solium taeniasis (EITB rES33). Findings Of 548 pigs, 256 (46.7%) were positive for antibodies against cysticercosis on EITB LLGP. Of 402 fecal samples, 6 (1.5%) were positive for the presence of Taenia sp. coproantigens. The proportion of coproantigen-positive individuals differed significantly between residents living within 100-meters of a tongue-positive pig (4/79, 5.1%) and residents living >100 meters from a tongue-positive pig (2/323, 0.6%) (p = 0.02). The prevalence of taeniasis was >8 times higher among residents living within 100 meters of a tongue-positive pig compared to residents living outside this range (adjusted PR 8.1, 95% CI 1.4–47.0). Conclusions Tongue-positive pigs in endemic communities can indicate geospatial foci in which the risk for taeniasis is increased. Targeted screening or presumptive treatment for taeniasis within these high-risk foci may be an effective and practical control intervention for rural endemic areas.

Cysticercosis Control: Bringing Advances to the Field

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.

Porcine cysticercosis: Possible cross-reactivity of taenia hydatigena to GP50 antigen in the enzyme-linked immunoelectrotransfer blot assay

Progress towards Taenia solium control is evident in the development of new technologies and in increasing regional coordination, yet disease eradication remains unlikely in the near future. In the meantime, translation of research advances into functioning control programs is necessary to address the ongoing disease burden in endemic areas. Multiple screening assays, effective treatments for both human and porcine infection, and vaccines blocking transmission to pigs are currently available. Strategies based on identification and treatment of T. solium adult tapeworms, as well as interventions that block cysticercosis acquisition in pigs have temporarily reduced transmission. Building on these successes with controlled community trials in varying endemic scenarios will drive progress towards regional elimination.

Neurocysticercosis among people living near pigs heavily infected with cysticercosis in rural endemic Peru

The lentil lectin glycoprotein enzyme-linked immunoelectrotransfer blot (LLGP EITB, reported sensitivity 99% and specificity 100%) is used as a serologic marker of exposure to Taenia solium in pigs. However, only a limited number of parasites have been evaluated for cross reactivity. Pigs may host other related cestode infections, including Taenia hydatigena, which have not been formally evaluated for cross-reactions. We investigated a corral in Tumbes, Peru, a region where a cysticercosis elimination demonstration project was completed in 2012. In this corral, 14/19 (73.7%) 6-8-week-old piglets were reactive to GP50 on LLGP EITB, and all had circulating Taenia sp. antigens. From eight necropsied piglets; four were infected with T. hydatigena metacestodes whereas none had evidence of T. solium infection. Two resident dogs were subsequently confirmed to have T. hydatigena taeniasis. These results suggest GP50 cross-reactivity in T. hydatigena-infected pigs, although controlled experimental infection is needed to confirm this hypothesis.

Prevalence, age profile, and associated risk factors for hymenolepis nana infection in a large population-based study in Northern Peru

Neurocysticercosis causes substantial neurologic morbidity in endemic regions around the world. In this cross-sectional study, we describe the frequency of neurocysticercosis among a presumed high-risk group of people in an endemic community in northern Peru. Participants who screened positive on a nine-question seizure survey were evaluated clinically to diagnose epilepsy using International League Against Epilepsy criteria. Those with epilepsy were offered a noncontrast computerized tomography (CT) of the head. We also tested sera from all participants using the lentil lectin-bound glycoprotein enzyme-linked immunoelectrotransfer blot (EITB) to detect anti-cysticercus antibodies and enzyme-linked immunosorbent assay (ELISA) B60/B158 to detect cysticercosis antigens. Participants with strongly positive ELISA (ratio ≥ 3) were offered a noncontrast magnetic resonance imaging (MRI) of the brain. We diagnosed 16 cases of epilepsy among 527 people screened (lifetime prevalence 30 per 1,000). Twelve with epilepsy accepted CT scan and five (41.7%) had parenchymal calcifications. None had viable cysts. Of the 514 who provided a blood sample, 241 (46.9%) were seropositive by EITB and 12 (2.9%) were strongly positive by ELISA (ratio ≥ 3). Eleven accepted MRI and eight (72.3%) had neurocysticercosis, including five with extraparenchymal cysts, five with parenchymal vesicular cysts, and two with parenchymal granulomas. These findings show that clinically relevant forms of neurocysticercosis and epilepsy can be found by applying screening interventions in communities endemic to Taenia solium. Longitudinal controlled studies are needed to better understand which subgroups are at highest risk and which are most likely to have improved prognosis as a result of screening.