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.

Elimination of Taenia solium Transmission in Northern Peru.

BACKGROUND: Taeniasis and cysticercosis are major causes of seizures and epilepsy. Infection by the causative parasite Taenia solium requires transmission between humans and pigs. The disease is considered to be eradicable, but data on attempts at regional elimination are lacking. We conducted a three-phase control program in Tumbes, Peru, to determine whether regional elimination would be feasible. METHODS: We systematically tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru. In phase 1, we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. In phase 2, we compared mass treatment with mass screening (each either with or without vaccination of pigs) in 17 villages. In phase 3, we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes (107 villages comprising 81,170 people and 55,638 pigs). The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live, nondegenerated cysts capable of causing new infection. The necropsy sampling was weighted in that we preferentially included more samples from seropositive pigs than from seronegative pigs. RESULTS: Only two of the strategies implemented in phase 1 resulted in limited control over the transmission of T. solium infection, which highlighted the need to intensify the subsequent strategies. After the strategies in phase 2 were implemented, no cyst that was capable of further transmission of T. solium infection was found among 658 sampled pigs. One year later, without further intervention, 7 of 310 sampled pigs had live, nondegenerated cysts, but no infected pig was found in 11 of 17 villages, including all the villages in which mass antiparasitic treatment plus vaccination was implemented. After the final strategy was implemented in phase 3, a total of 3 of 342 pigs had live, nondegenerated cysts, but no infected pig was found in 105 of 107 villages. CONCLUSIONS: We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru. (Funded by the Bill and Melinda Gates Foundation and others.).

Interspecies interactions and potential Influenza A virus risk in small swine farms in Peru.

BACKGROUND: The recent avian influenza epidemic in Asia and the H1N1 pandemic demonstrated that influenza A viruses pose a threat to global public health. The animal origins of the viruses confirmed the potential for interspecies transmission. Swine are hypothesized to be prime "mixing vessels" due to the dual receptivity of their trachea to human and avian strains. Additionally, avian and human influenza viruses have previously been isolated in swine. Therefore, understanding interspecies contact on smallholder swine farms and its potential role in the transmission of pathogens such as influenza virus is very important. METHODS: This qualitative study aimed to determine swine-associated interspecies contacts in two coastal areas of Peru. Direct observations were conducted at both small-scale confined and low-investment swine farms (n = 36) and in open areas where swine freely range during the day (n = 4). Interviews were also conducted with key stakeholders in swine farming. RESULTS: In both locations, the intermingling of swine and domestic birds was common. An unexpected contact with avian species was that swine were fed poultry mortality in 6/20 of the farms in Chancay. Human-swine contacts were common, with a higher frequency on the confined farms. Mixed farming of swine with chickens or ducks was observed in 36% of all farms. Human-avian interactions were less frequent overall. Use of adequate biosecurity and hygiene practices by farmers was suboptimal at both locations. CONCLUSIONS: Close human-animal interaction, frequent interspecies contacts and suboptimal biosecurity and hygiene practices pose significant risks of interspecies influenza virus transmission. Farmers in small-scale swine production systems constitute a high-risk population and need to be recognized as key in preventing interspecies pathogen transfer. A two-pronged prevention approach, which offers educational activities for swine farmers about sound hygiene and biosecurity practices and guidelines and education for poultry farmers about alternative approaches for processing poultry mortality, is recommended. Virological and serological surveillance for influenza viruses will also be critical for these human and animal populations.

Neurocysticercosis among People Living Near Pigs Heavily Infected with Cysticercosis in Rural Endemic 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.

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.

Assessing Ultrasonography as a Diagnostic Tool for Porcine Cysticercosis.

BACKGROUND: Taenia solium inflicts substantial neurologic disease and economic losses on rural communities in many developing nations. "Ring-strategy" is a control intervention that targets treatment of humans and pigs among clusters of households (rings) that surround pigs heavily infected with cysticerci. These pigs are typically identified by examining the animal's tongue for cysts. However, as prevalence decreases in intervened communities, more sensitive methods may be needed to identify these animals and to maintain control pressure. The purpose of this study was to evaluate ultrasonography as an alternative method to detect pigs heavily infected with T. solium cysts. METHODOLOGY/PRINCIPAL FINDINGS: We purchased 152 pigs representing all seropositive animals villagers were willing to sell from eight communities (pop. 2085) in Piura, Peru, where T. solium is endemic. Tongue and ultrasound examinations of the fore and hind-limbs were performed in these animals, followed by necropsy with fine dissection as gold standard to determine cyst burden. We compared the sensitivity and specificity of ultrasonography with tongue examination for their ability to detect heavy infection (≥ 100 viable cysts) in pigs. Compared to tongue examination, ultrasonography was more sensitive (100% vs. 91%) but less specific (90% vs. 98%), although these differences were not statistically significant. The greater sensitivity of ultrasound resulted in detection of one additional heavily infected pig compared to tongue examination (11/11 vs. 10/11), but resulted in more false positives (14/141 vs. 3/141) due to poor specificity. CONCLUSIONS/SIGNIFICANCE: Ultrasonography was highly sensitive in detecting heavily infected pigs and may identify more rings for screening or treatment compared to tongue examination. However, the high false positive rate using ultrasound would result in substantial unnecessary treatment. If specificity can be improved with greater operator experience, ultrasonography may benefit ring interventions where control efforts have stalled due to inadequate sensitivity of tongue examination.

Spatial relationship between Taenia solium tapeworm carriers and necropsy cyst burden in pigs.

BACKGROUND: Taenia solium, a parasite that affects humans and pigs, is the leading cause of preventable epilepsy in the developing world. Geographic hotspots of pigs testing positive for serologic markers of T. solium exposure have been observed surrounding the locations of human tapeworm carriers. This clustered pattern of seropositivity in endemic areas formed the basis for geographically targeted control interventions, which have been effective at reducing transmission. In this study, we further explore the spatial relationship between human tapeworm carriers and infected pigs using necroscopic examination as a quantitative gold-standard diagnostic to detect viable T. solium cyst infection in pigs. METHODOLOGY/PRINCIPAL FINDINGS: We performed necroscopic examinations on pigs from 7 villages in northern Peru to determine the number of viable T. solium cysts in each pig. Participating humans in the study villages were tested for T. solium tapeworm infection (i.e., taeniasis) with an ELISA coproantigen assay, and the distances from each pig to its nearest human tapeworm carrier were calculated. We assessed the relationship between proximity to a tapeworm carrier and the prevalence of light, moderate, and heavy cyst burden in pigs. The prevalence of pig infection was greatest within 50 meters of a tapeworm carrier and decreased monotonically as distance increased. Pigs living less than 50 meters from a human tapeworm carrier were 4.6 times more likely to be infected with at least one cyst than more distant pigs. Heavier cyst burdens, however, were not more strongly associated with proximity to tapeworm carriers than light cyst burdens. CONCLUSION/SIGNIFICANCE: Our study shows that human tapeworm carriers and pigs with viable T. solium cyst infection are geographically correlated in endemic areas. This finding supports control strategies that treat humans and pigs based on their proximity to other infected individuals. We did not, however, find sufficient evidence that heavier cyst burdens in pigs would serve as improved targets for geographically focused control interventions.

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

BACKGROUND: Taenia solium, a parasitic cestode that affects humans and pigs, is the leading cause of preventable epilepsy in the developing world. T. solium 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 T. solium transmission, such as open human defecation and dense pig activity, are concentrated. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

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.

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.

Neurocysticercosis as a cause of epilepsy and seizures in two community-based studies in a cysticercosis-endemic region in Peru.

BACKGROUND: The prevalence of epilepsy added to inadequate treatment results in chronic morbidity and considerable mortality in poor populations. Neurocysticercosis (NCC), a helminthic disease of the central nervous system, is a leading cause of seizures and epilepsy in most of the world. METHODS: Taking advantage of a cysticercosis elimination program, we performed two community-based cross-sectional studies between 2006 and 2007 in 58 rural communities (population 20,610) to assess the prevalence and characteristics of epilepsy and epileptic seizures in this endemic region. Serological and computed tomography (CT) data in individuals with epilepsy were compared to previous surveys in general population from the same region. PRINCIPAL FINDINGS: In two surveys, 17,450 individuals were evaluated. Lifetime prevalence of epilepsy was 17.25/1000, and prevalence of active epilepsy was 10.8/1000 inhabitants. The prevalence of epilepsy increased after age 25 years and dropped after age 45. Only 24% (45/188) of patients with active epilepsy were taking antiepileptic drugs, all at sub-therapeutic doses. Antibodies to cysticercosis were found in approximately 40% of individuals with epilepsy in both studies. In one survey only individuals presenting strong antibody reactions were significantly associated with having epilepsy (OR 5.74; p<0.001). In the second, the seroprevalence as well as the proportion presenting strong antibody reactions were both significantly higher in individuals with epilepsy (OR 2.2 and 4.33, respectively). Brain CT showed NCC-compatible images in 109/282 individuals with epilepsy (39%). All individuals with viable parasites on CT were seropositive. CONCLUSION: The prevalence of epilepsy in this cysticercosis endemic region is high and NCC is an important contributor to it.

Geographic correlation between tapeworm carriers and heavily infected cysticercotic pigs.

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.

Detection of Taenia solium taeniasis coproantigen is an early indicator of treatment failure for taeniasis.

Taenia solium causes taeniasis and cysticercosis, a zoonotic complex associated with a significant burden of epilepsy in most countries. Reliable diagnosis and efficacious treatment of taeniasis are needed for disease control. Currently, cure can be confirmed only after a period of at least 1 month, by negative stool microscopy. This study assessed the performance of detection by a coproantigen enzyme-linked immunosorbent assay (CoAg-ELISA) for the early evaluation of the efficacy of antiparasitic treatment of human T. solium taeniasis. We followed 69 tapeworm carriers who received niclosamide as standard treatment. Stool samples were collected on days 1, 3, 7, 15, 30, and 90 after treatment and were processed by microscopy and CoAg-ELISA. The efficacy of niclosamide was 77.9% (53/68). Thirteen patients received a second course of treatment and completed the follow-up. CoAg-ELISA was therefore evaluated for a total of 81 cases (68 treatments, 13 retreatments). In successful treatments (n = 64), the proportion of patients who became negative by CoAg-ELISA was 62.5% after 3 days, 89.1% after 7 days, 96.9% after 15 days, and 100% after 30 days. In treatment failures (n = 17), the CoAg-ELISA result was positive for 70.6% of patients after 3 days, 94.1% after 7 days, and 100% after 15 and 30 days. Only 2 of 17 samples in cases of treatment failure became positive by microscopy by day 30. The presence of one scolex, but not multiple scolices, in posttreatment stools was strongly associated with cure (odds ratio [OR], 52.5; P < 0.001). CoAg-ELISA is useful for the assessment of treatment failure in taeniasis. Early assessment at day 15 would detect treatment failure before patients become infective.