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.

Identification of wild rodents as intermediate hosts for Hydatigera taeniaeformis in Peru.

Hydatigera taeniaeformis is a cestode that uses felines and rodents as definitive and intermediate hosts, respectively. Its larval stage, or metacestode, infects a wide variety of rodent species and develops in the liver parenchyma into a cyst. The aim of this study was to evaluate the occurrence of H. taeniaeformis metacestode in various species of wild rodents from Peru. For this, the livers of 356 rodents were macroscopically examined for any parasitic form compatible with metacestodes. Metacestodes were identified by measuring characteristic morphological parameters, and the diagnosis was confirmed by molecular analysis of a fragment of the cytochrome c oxidase subunit 1 gene (cox1). Five rodents: two small-eared pygmy rice rats (Oligoryzomys microtis), two white-naped squirrels (Simosciurus nebouxii), and one pygmy rice rat (Oligoryzomys sp.) were infected with H. taeniaeformis metacestodes. The cox1 sequences from our metacestodes showed up to 100% identity with previous H. taeniaeformis sequences from the GenBank. These results demonstrated the occurrence of H. taeniaeformis in new intermediate hosts, as well as the first molecular contribution for H. taeniaeformis from Peru.

Improved Diagnosis of Viable Parenchymal Neurocysticercosis by Combining Antibody Banding Patterns on Enzyme-Linked Immunoelectrotransfer Blot (EITB) with Antigen Enzyme-Linked Immunosorbent Assay (ELISA).

The diagnosis of neurocysticercosis (NCC) depends on neuroimaging and serological confirmation. While antibody detection by enzyme-linked immunoelectrotransfer blot (EITB) fails to predict viable NCC, EITB banding patterns provide information about the host's infection course. Adding antigen enzyme-linked immunosorbent assay (Ag-ELISA) results to EITB banding patterns may improve their ability to predict or rule out of viable NCC. We assessed whether combining EITB banding patterns with Ag-ELISA improves discrimination of viable infection in imaging-confirmed parenchymal NCC. EITB banding patterns were grouped into classes using latent class analysis. True-positive and false-negative Ag-ELISA results in each class were compared using Fisher's exact test. Four classes were identified: 1, EITB negative or positive to GP50 alone (GP50 antigen family); 2, positive to GP42-39 and GP24 (T24/42 family), with or without GP50; and 3 and 4, positive to GP50, GP42-39, and GP24 and reacting to bands in the 8-kDa family. Most cases in classes 3 and 4 had viable NCC (82% and 88%, respectively) compared to classes 2 and 1 (53% and 5%, respectively). Adding positive Ag-ELISA results to class 2 predicted all viable NCC cases (22/22 [100%]), whereas 11/40 patients (27.5%) Ag-ELISA negative had viable NCC (P < 0.001). Only 1/4 patients (25%) Ag-ELISA positive in class 1 had viable NCC, whereas 1/36 patients (2.8%) Ag-ELISA negative had viable NCC (P = 0.192). In classes 3 and 4, adding Ag-ELISA was not contributory. Combining Ag-ELISA with EITB banding patterns improves discrimination of viable from nonviable NCC, particularly for class 2 responses. Together, these complement neuroimaging more appropriately for the diagnosis of viable NCC.

Taenia solium Cysticercosis and Its Impact in Neurological Disease.

Taenia solium neurocysticercosis (NCC) is endemic in most of the world and contributes significantly to the burden of epilepsy and other neurological morbidity. Also present in developed countries because of immigration and travel, NCC is one of few diseases targeted for eradication. This paper reviews all aspects of its life cycle (taeniasis, porcine cysticercosis, human cysticercosis), with a focus on recent advances in its diagnosis, management, and control. Diagnosis of taeniasis is limited by poor availability of immunological or molecular assays. Diagnosis of NCC rests on neuroimaging findings, supported by serological assays. The treatment of NCC should be approached in the context of the particular type of infection (intra- or extraparenchymal; number, location, and stage of lesions) and has evolved toward combined symptomatic and antiparasitic management, with particular attention to modulating inflammation. Research on NCC and particularly the use of recently available genome data and animal models of infection should help to elucidate mechanisms of brain inflammation, damage, and epileptogenesis.

Frequency and Determinant Factors for Calcification in Neurocysticercosis.

BACKGROUND: Neurocysticercosis is a major cause of acquired epilepsy. Larval cysts in the human brain eventually resolve and either disappear or leave a calcification that is associated with seizures. In this study, we assessed the proportion of calcification in parenchymal neurocysticercosis and risk factors associated with calcification. METHODS: Data for 220 patients with parenchymal NCC from 3 trials of antiparasitic treatment were assessed to determine what proportion of the cysts that resolved 6 months after treatment ended up in a residual calcification at 1 year. Also, we evaluated the risk factors associated with calcification. RESULTS: The overall proportion of calcification was 38% (188/497 cysts, from 147 patients). Predictors for calcification at the cyst level were cysts larger than 14 mm (risk ratio [RR], 1.34; 95% confidence interval [CI], 1.02-1.75) and cysts with edema at baseline (RR, 1.39; 95% CI, 1.05-1.85). At the patient level, having had more than 24 months with seizures (RR, 1.25; 95% CI, 1.08-1.46), mild antibody response (RR, 1.14; 95% CI, 1.002-1.27), increased dose albendazole regime (RR, 1.26; 95% CI, 1.14-1.39), lower doses of dexamethasone (RR, 1.36; 95% CI, 1.02-1.81), not receiving early antiparasitic retreatment (RR, 1.45; 95% CI, 1.08-1.93), or complete cure (RR, 1.48; 95% CI, 1.29-1.71) were associated with a increased risk of calcification. CONCLUSIONS: Approximately 38% of parenchymal cysts calcify after antiparasitic treatment. Some factors associated with calcification are modifiable and may be considered to decrease or avoid calcification, potentially decreasing the risk for seizure relapses.

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.

Prevalence and molecular characterization of Sarcoptes scabiei from vicuñas (Vicugna vicugna) from Southern Peruvian Andes.

Sarcoptic mange is a disease caused by an infectious parasite in the vicuñas (Vicugna vicugna) from South America. Although molecular studies have provided much information about the epidemiology of this disease, this information is still unknown in vicuñas. This study determined the prevalence and molecular characterization of Sarcoptes scabiei from vicuñas from Southern Peruvian Andes. During the 2018 shearing season, 181 vicuñas were clinically evaluated for lesions compatible with mange. Sarcoptes scabiei was detected in 35 (19.3%) vicuñas, and 50 mites from 25 vicuñas were selected for molecular analyses of the mitochondrial (cox1) and nuclear (ITS2) genetic markers. Molecular analyses of the cox1 and ITS2 sequences showed an identity of 94­99% and 99.8­100% with previous S. scabiei sequences registered in the GenBank, respectively. Sequence polymorphisms were more evident in the ITS2 than in the cox1, but only the cox1 had an association with the host. Phylogenetic analysis of S. scabiei cox1 sequences from vicuñas showed a cluster with S. scabiei cox1 sequences from canids, suggesting that the origin of S. scabiei from vicuña is associated with canid mites. This research is the first molecular analysis of S. scabiei from vicuñas. Future molecular studies will be necessary to determine the species variety, geographic segregation and host­parasite adaptation for this vicuña's mite.

Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Adults in an Open-Label Phase 1 Multiple Ascending Dose and Food Effect Study.

Neurocysticercosis and trichuriasis are difficult-to-treat parasitic infections that affect more than 1.5 billion people worldwide. Oxfendazole, a potent broad-spectrum benzimidazole anthelmintic approved for use in veterinary medicine, has shown substantial antiparasitic activity against neurocysticercosis and intestinal helminths in preclinical studies. As part of a program to transition oxfendazole from veterinary medicine to human use, phase I multiple ascending dose and food effect studies were conducted. Thirty-six healthy adults were enrolled in an open-label study which evaluated (i) the pharmacokinetics and safety of oxfendazole following multiple ascending doses of oxfendazole oral suspension at 3, 7.5, and 15 mg/kg once daily for 5 days and (ii) the effect of food on oxfendazole pharmacokinetics and safety after a single 3-mg/kg dose administered following an overnight fast or the consumption of a fatty breakfast. Following multiple oral dose administration, the intestinal absorption of oxfendazole was rapid, with the time to maximum concentration of drug in serum (Tmax) ranging from 1.92 to 2.56 h. A similar half-life of oxfendazole (9.21 to 11.8 h) was observed across all dose groups evaluated, and oxfendazole exhibited significantly less than a dose-proportional increase in exposure. Oxfendazole plasma exposures were higher in female subjects than in male subjects. Following daily administration, oxfendazole reached a steady state in plasma on study day 3, with minimal accumulation. Food delayed the oxfendazole Tmax by a median of 6.88 h and resulted in a 49.2% increase in the maximum observed drug concentration in plasma (Cmax) and an 86.4% increase in the area under the concentration-time curve (AUC). Oxfendazole was well tolerated in all study groups, and there were no major safety signals identified in this study. (This study has been registered at ClinicalTrials.gov under identifier NCT03035760.).

Cryptosporidium parvum as a risk factor of diarrhea occurrence in neonatal alpacas in Peru.

Cryptosporidiosis has been reported as an important cause of neonatal diarrhea and mortality in cattle, sheep, and other ruminants, but its impact on alpaca health has not been studied thoroughly. In this study, we have determined the prevalence and evaluated the role of cryptosporidiosis as a risk factor for diarrhea occurrence in newborn alpacas. During the calving season (January-March) of 2006, stool specimens (N = 1312) were collected from 24 herds of newborn alpacas in Puno and Cuzco, departments that account for the largest populations of alpacas in Peru. All the specimens were microscopically screened for Cryptosporidium spp. using the acid-fast technique. The association between Cryptosporidium detection and diarrhea was analyzed using χ2 test and generalized lineal model. Cryptosporidium species were determined by PCR-RFLP analysis of the small subunit rRNA gene. Cryptosporidium oocysts were detected in 159 of 1312 (12.4%) newborn alpacas. Results of the analyses demonstrated that crypstosporidiosis was significantly associated with diarrhea (PR = 3.84; CI95% 2.54-5.81; p < 0.0001). Only Cryptosporidium parvum was detected in the 153 Cryptosporidium-infected animals. Thus, there is an association of C. parvum infection with diarrhea in neonatal alpacas.

Albendazole Sulfoxide Plasma Levels and Efficacy of Antiparasitic Treatment in Patients With Parenchymal Neurocysticercosis.

BACKGROUND: The efficacy of albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of albendazole sulfoxide (ASOX), the active metabolite of albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS: ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS: There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS: We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.

Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study.

Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.).

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.).

Correction to: Molecular characterization of the Taenia solium Tso31 antigen and homologous of other Taenia species from Peru.

The original version of this article contained a mistake.

Molecular characterization of the Taenia solium Tso31 antigen and homologous of other Taenia species from Peru.

Several studies have been performed to determine specific antigens for the diagnosis of tapeworms. One of these antigens is Tso31, which is used to differentiate Taenia solium and Taenia saginata in human feces. The aim of the present work was the molecular characterization of this protein in different tapeworm specimens collected in Peru: T. omisa (n = 6), T. hydatigena (n = 7), T. taeniaeformis (n = 4), T. pisiformes (n = 1), T. multiceps (n = 7), and T. solium (n = 10). Total DNA was extracted from each proglottid using a commercial DNA kit for tissue. A nested PCR was used to amplify a fragment of the previously described oncosphere-specific protein Tso31 gene. The nested PCR products were analyzed by 1.5% agarose gel electrophoresis and visualized after ethidium bromide staining. All nested PCR-positive products were sequenced and their sequences were compared. Of all the tapeworms analyzed, only T. solium and T. multiceps amplified the Tso31 gene. All sequences were identical for each species. Our T. solium Tso31 showed 100% similarity when compared with published GenBank sequences. The difference between T. solium and T. multiceps Tso31 samples was 8.1%. In conclusion, our results show that the tsol31 gene is not exclusive to T. solium.

Antibody Banding Patterns of the Enzyme-Linked Immunoelectrotransfer Blot and Brain Imaging Findings in Patients With Neurocysticercosis.

Background: The enzyme-linked immunoelectrotransfer blot (EITB) assay is the reference serological test for neurocysticercosis (NCC). A positive result on EITB does not always correlate with the presence of active infections in the central nervous system (CNS), and patients with a single viable brain cyst may be EITB negative. Nonetheless, EITB antibody banding patterns appears to be related with the expression of 3 protein families of Taenia solium, and in turn with the characteristics of NCC in the CNS (type, stage, and burden of viable cysts). Methods: We evaluated EITB antibody banding patterns and brain imaging findings of 548 NCC cases. Similar banding patterns were grouped into homogeneous classes using latent class analysis. The association between classes and brain imaging findings was assessed. Results: Four classes were identified. Class 1 (patients negative or only positive to the GP50 band, related to the protein family of the same name) was associated with nonviable or single viable parenchymal cysticerci; class 2 (patients positive to bands GP42-39 and GP24, related to the T24-42 protein family, with or without anti-GP50 antibodies) was associated with intraparenchymal viable and nonviable infections; classes 3 and 4 (positive to GP50, GP42-39, and GP24 but also responding to low molecular weight bands GP21, GP18, GP14, and GP13, related to the 8 kDa protein family) were associated with extraparenchymal and intraparenchymal multiple viable cysticerci. Conclusions: EITB antibody banding patterns correlate with brain imaging findings and complement imaging information for the diagnosis of NCC and for staging NCC patients.

Low sensitivity and frequent cross-reactions in commercially available antibody detection ELISA assays for Taenia solium cysticercosis.

OBJECTIVE: To evaluate the diagnostic performance of two commercially available ELISA kits, Novalisa® and Ridascreen® , for the detection of antibodies to Taenia solium, compared to serological diagnosis of neurocysticercosis (NCC) by LLGP-EITB (electro-immunotransfer blot assay using lentil-lectin purified glycoprotein antigens). METHODS: Archive serum samples from patients with viable NCC (n = 45) or resolved, calcified NCC (n = 45), as well as sera from patients with other cestode parasites (hymenolepiasis, n = 45 and cystic hydatid disease, n = 45), were evaluated for cysticercosis antibody detection using two ELISA kits, Novalisa® and Ridascreen® . All NCC samples had previously tested positive, and all samples from heterologous infections were negative on LLGP-EITB for cysticercosis. Positive rates were calculated by kit and sample group and compared between the two kits. RESULTS: Compared to LLGP-EITB, the sensitivity of both ELISA assays to detect specific antibodies in patients with viable NCC was low (44.4% and 22.2%), and for calcified NCC, it was only 6.7% and 4.5%. Sera from patients with cystic hydatid disease were highly cross-reactive in both ELISA assays (38/45, 84.4%; and 25/45, 55.6%). Sera from patients with hymenolepiasis cross-reacted in five cases in one of the assays (11.1%) and in only one sample with the second assay (2.2%). CONCLUSIONS: The performance of Novalisa® and Ridascreen® was poor. Antibody ELISA detection cannot be recommended for the diagnosis of neurocysticercosis.

Cysticidal Efficacy of Combined Treatment With Praziquantel and Albendazole for Parenchymal Brain Cysticercosis.

BACKGROUND: The efficacy of current antiparasitic treatment for cerebral Taenia solium cysticercosis with either albendazole (ABZ) or praziquantel (PZQ) is suboptimal. A recent study demonstrated that combining these 2 antiparasitic drugs improves antiparasitic efficacy. We present here the parasiticidal efficacy data obtained during a previous phase II pharmacokinetic study that compared combined ABZ plus PZQ with ABZ alone. METHODS: The study was a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ (15 mg/k/d, for 10 days) and PZQ (50 mg/k/d, for 10 days) in intraparenchymal brain cysticercosis. Patients received the usual concomitant medications, including an antiepileptic drug (phenytoin or carbamazepine), dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug. Patients underwent safety laboratory evaluations at days 4, 7, and 11, as well as magnetic resonance (MR) imaging at 6 months to assess parasiticidal efficacy. RESULTS: Thirty-two patients were included, 16 in each arm. All of them completed antiparasitic treatment and underwent follow-up brain MR imaging. Cysticidal efficacy was strikingly higher in the combined ABZ-plus-PZQ group than in the ABZ-alone group (proportion of cysts resolved, 78 of 82 [95%] vs 23 of 77 [30%] [relative risk {RR}, 3.18; 95% confidence interval {CI}, 2.08-4.88; P < .001]; patients with complete cyst clearance, 12 of 16 [75%] vs 4 of 16 [25%] [RR, 3.00; 95% CI, 1.23-7.34; P = .005]). CONCLUSIONS: The combination of ABZ plus PZQ is more effective in destroying viable brain cysticercosis cysts than ABZ alone. CLINICAL TRIALS REGISTRATION: NCT00441285.

Evaluation of a New Immunochromatographic Test Using Recombinant Antigen B8/1 for Diagnosis of Cystic Echinococcosis.

Diagnosis of cystic echinococcosis (CE) is based on the identification of the cyst(s) by imaging, using immunodiagnostic tests mainly as complementary tools in clinical settings. Among the antigens used for immunodiagnosis, previous studies described a good performance of the recombinant antigen B8/1 (rAgB) in an enzyme-linked immunosorbent assay (ELISA) format; however, in remote parts of areas where the disease is endemic, the implementation of an ELISA is difficult, so a more simple, rapid, and reliable method such as the immunochromatographic test (ICT) is required. In this study, using a set of 50 serum samples from patients with surgically confirmed CE, we compared the performance of an ICT and that of an ELISA using the rAgB. The overall sensitivities of ICT and ELISA were not statistically different (78% versus 72%; P = 0.36). The overall agreement between both tests was moderate (κ = 0.41; P < 0.01). Concordance between ICT and ELISA was substantial or almost perfect for patients with liver involvement (κ = 0.65; P < 0.001) and patients with more than one hydatid cyst (κ = 0.82; P < 0.001), respectively. Moreover, specificity analysis using a total of 88 serum samples from healthy individuals (n = 20) and patients (n = 68) with other parasitic infections revealed that ICT had a specificity of 89.8%. ICT and ELISA had similar performance for the detection of specific antibodies to E. granulosus, and ICT had a high specificity, opening the possibility of using ICT as a screening tool in rural settings.

Seizures, cysticercosis and rural-to-urban migration: the PERU MIGRANT study.

OBJECTIVES: To examine the prevalence of seizures, epilepsy and seropositivity to cysticercosis in rural villagers (cysticercosis-endemic setting), rural-to-urban migrants into a non-endemic urban shanty town and urban inhabitants of the same non-endemic shanty town. METHODS: Three Peruvian populations (n = 985) originally recruited into a study about chronic diseases and migration were studied. These groups included rural inhabitants from an endemic region (n = 200), long-term rural-to-urban migrants (n = 589) and individuals living in the same urban setting (n = 196). Seizure disorders were detected by a survey, and a neurologist examined positive respondents. Serum samples from 981/985 individuals were processed for cysticercosis antibodies on immunoblot. RESULTS: Epilepsy prevalence (per 1000 people) was 15.3 in the urban group, 35.6 in migrants and 25 in rural inhabitants. A gradient in cysticercosis antibody seroprevalence was observed: urban 2%, migrant 13.5% and rural group 18% (P < 0.05). A similarly increasing pattern of higher seroprevalence was observed among migrants by age at migration. In rural villagers, there was strong evidence of an association between positive serology and having seizures (P = 0.011) but such an association was not observed in long-term migrants or in urban residents. In the entire study population, compared with seronegative participants, those with strong antibody reactions (≥ 4 antibody bands) were more likely to have epilepsy (P < 0.001). CONCLUSIONS: It is not only international migration that affects cysticercosis endemicity; internal migration can also affect patterns of endemicity within an endemic country. The neurological consequences of cysticercosis infection likely outlast the antibody response for years after rural-to-urban migration.

Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: toward first in human studies.

A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases.