James C. Allan

Proposed diagnostic criteria for neurocysticercosis.

Neurocysticercosis is the most common helminthic infection of the CNS but its diagnosis remains difficult. Clinical manifestations are nonspecific, most neuroimaging findings are not pathognomonic, and some serologic tests have low sensitivity and specificity. The authors provide diagnostic criteria for neurocysticercosis based on objective clinical, imaging, immunologic, and epidemiologic data. These include four categories of criteria stratified on the basis of their diagnostic strength, including the following: 1) absolute—histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion, cystic lesions showing the scolex on CT or MRI, and direct visualization of subretinal parasites by funduscopic examination; 2) major—lesions highly suggestive of neurocysticercosis on neuroimaging studies, positive serum enzyme-linked immunoelectrotransfer blot for the detection of anticysticercal antibodies, resolution of intracranial cystic lesions after therapy with albendazole or praziquantel, and spontaneous resolution of small single enhancing lesions; 3) minor—lesions compatible with neurocysticercosis on neuroimaging studies, clinical manifestations suggestive of neurocysticercosis, positive CSF enzyme-linked immunosorbent assay for detection of anticysticercal antibodies or cysticercal antigens, and cysticercosis outside the CNS; and 4) epidemiologic—evidence of a household contact with Taenia solium infection, individuals coming from or living in an area where cysticercosis is endemic, and history of frequent travel to disease-endemic areas. Interpretation of these criteria permits two degrees of diagnostic certainty: 1) definitive diagnosis, in patients who have one absolute criterion or in those who have two major plus one minor and one epidemiologic criterion; and 2) probable diagnosis, in patients who have one major plus two minor criteria, in those who have one major plus one minor and one epidemiologic criterion, and in those who have three minor plus one epidemiologic criterion.

Current Consensus Guidelines for Treatment of Neurocysticercosis

SUMMARY Taenia solium neurocysticercosis is a common cause of epileptic seizures and other neurological morbidity in most developing countries. It is also an increasingly common diagnosis in industrialized countries because of immigration from areas where it is endemic. Its clinical manifestations are highly variable and depend on the number, stage, and size of the lesions and the hosts immune response. In part due to this variability, major discrepancies exist in the treatment of neurocysticercosis. A panel of experts in taeniasis/cysticercosis discussed the evidence on treatment of neurocysticercosis for each clinical presentation, and we present the panels consensus and areas of disagreement. Overall, four general recommendations were made: (i) individualize therapeutic decisions, including whether to use antiparasitic drugs, based on the number, location, and viability of the parasites within the nervous system; (ii) actively manage growing cysticerci either with antiparasitic drugs or surgical excision; (iii) prioritize the management of intracranial hypertension secondary to neurocysticercosis before considering any other form of therapy; and (iv) manage seizures as done for seizures due to other causes of secondary seizures (remote symptomatic seizures) because they are due to an organic focus that has been present for a long time.

DNA Differential Diagnosis of Taeniasis and Cysticercosis by Multiplex PCR

ABSTRACT Multiplex PCR was established for differential diagnosis of taeniasis and cysticercosis, including their causative agents. For identification of the parasites, multiplex PCR with cytochrome c oxidase subunit 1 gene yielded evident differential products unique for Taenia saginata and Taenia asiatica and for American/African and Asian genotypes of Taenia solium with molecular sizes of 827, 269, 720, and 984 bp, respectively. In the PCR-based detection of tapeworm carriers using fecal samples, the diagnostic markers were detected from 7 of 14 and 4 of 9 T. solium carriers from Guatemala and Indonesia, respectively. Test sensitivity may have been reduced by the length of time (up to 12 years) that samples were stored and/or small sample volumes (ca. 30 to 50 mg). However, the diagnostic markers were detected by nested PCR in five worm carriers from Guatemalan cases that were found to be negative by multiplex PCR. It was noteworthy that a 720 bp-diagnostic marker was detected from a T. solium carrier who was egg-free, implying that it is possible to detect worm carriers and treat before mature gravid proglottids are discharged. In contrast to T. solium carriers, 827-bp markers were detected by multiplex PCR in all T. saginata carriers. The application of the multiplex PCR would be useful not only for surveillance of taeniasis and cysticercosis control but also for the molecular epidemiological survey of these cestode infections.

Immunodiagnostic tools for taeniasis

Most diagnostic work conducted on the Taenia species zoonoses has been carried out on the larval stage of Taenia solium in man, reflecting the relative severity of the pathology caused by this stage of that organism. This review will, however, concentrate on the immunodiagnosis of the adult intestinal stages of these parasites in humans. Diagnosis of T. solium will be examined in most detail because of the relative importance of this parasite but relevant work from other cestodes of man and animals will also be discussed. In addition both classical and molecular approaches to diagnosis will be briefly covered. There have been a number of advances in immunodiagnosis of taeniasis over recent years that have improved both diagnostic sensitivity and specificity. Techniques for the detection of Taenia specific coproantigens in human taeniasis infections have been shown to more than double the numbers of T. solium cases accurately diagnosed in epidemiological studies. More recently, work on the serological diagnosis of T. solium have led to the development of a sensitive and specific enzyme linked immuno-transfer blot for the detection of species and stage specific circulating antibodies to adult worm excretory-secretory antigens. Work is ongoing to further improve these assays.

An epidemiological study of epilepsy and epileptic seizures in two rural Guatemalan communities.

A cross-sectional epidemiological study of two communities in Guatemala, EI Jocote and Quesada, was conducted to determine the prevalence of epilepsy and epileptic seizures. An initial screening questionnaire was applied to detect individuals who had possibly suffered seizures in the past. These individuals were then examined more thoroughly by a neurologist, to confirm or reject them as cases of epilepsy. The crude prevalences of epilepsy so revealed were 28 cases/1000 in EI Jocote and 29 cases/1000 in Quesada. The prevalence of active epilepsy in each community was approximately 18 cases/thousand. The most common type of seizure suffered was of the generalised tonic-clonic type. Seventy-six of the individuals who had a history of epileptic seizures and 51 individuals from the same communities with no such history were then given brain scans, using computerized axial tomography. These neuro-imaging studies revealed some form of abnormal image in 33% (17) of the subjects with no history of seizures and 70% (53) of those with a history of seizures (χ2= = 12.2; P < 0.00006). The frequency of detected brain abnormalities in the individuals who had suffered a single episode of seizures was similar to that in those who were classified as epileptic. The most commonly observed type of abnormality was punctate calcification, followed by cerebral oedema and hypodensities. The reasons for the high prevalences of epilepsy, epileptic seizures and abnormal neuro-images observed in the present study merit further investigation. Although neurocysticercosis caused by Taenia solium was thought to be a significant cause of the epilepsy occurring in the study communities, many apparently non-epileptic individuals have brain lesions indicative of this disease.

Epidemiological study of Taenia solium taeniasis/cysticercosis in a rural village in Yucatan state, Mexico

A survey to detect human taeniasis and cysticercosis was conducted in a community in Yucatan state, Mexico, an area endemic for Taenia solium. Information on the environmental, demographic and risk factors associated with transmission of T. solium within the community was recorded on questionnaires. Although no Taenia eggs or proglottides were found in the initial faecal samples collected from each of the 475 subjects, the results of a capture-ELISA for T. solium coproantigen were positive for 10 of the subjects (of both genders and various ages). After treatment with niclosamide, proglottides were detected in purge samples from seven of these 10 subjects. The prevalence of parasitologically confirmed taeniasis was therefore 1.5% (seven in 475). The other three ELISA-positive cases delayed supplying faecal material post-treatment, and it is nuclear whether they had expelled proglottides before providing the samples. All 10 ELISA-positive subjects became ELISA-negative after treatment. Seroprevalence of human cysticercosis, based on the detection in immunoblots of antibodies to antigens of 8- and 26-kDa from a crude saline extract of T. solium metacestodes, was 3.7% (i.e. five positives out of 134 subjects). None of the seropositive cases demonstrated clinical symptoms of infection. Again, the positive cases were of both genders and various ages. Although tongue palpation indicated that 17 (23%) of 75 pigs kept within the community had T. solium cysticercosis, the results of immunoblotting demonstrated antibodies to the 8- and/or 26-kDa antigens of T. solium in 26 (35%). The pigs allowed to roam throughout the community were far more likely to have cysticercosis than those kept in pens (odds ratio = 42, with a 95% confidence interval of 5.05-920.2; P < 0.00001). Not surprisingly, the risk factors associated with human taeniasis and cysticercosis included the eating of infected pork and close proximity to a carrier of T. solium. The main risk factor identified for porcine cysticercosis was free-range husbandry, permitting access to human faeces. This is the first comprehensive report of taeniasis and cysticercosis in a rural population from the Yucatan peninsula of Mexico.

Dipstick dot ELISA for the detection of Taenia coproantigens in humans

A dipstick dot ELISA for detection of Taenia-specific coproantigens was developed. The test was based on a sandwich ELISA using antibodies raised against adult Taenia solium. Antibodies were absorbed to nitrocellulose paper previously adhered to acetate plastic to form dipsticks. Once blocked with 5% skimmed milk and dried the antibody-coated dipsticks were stable for several weeks at room temperature. Both micro and dot ELISA formats were genus specific although the dot ELISA was less sensitive than the micro ELISA based on the same antiserum. During field studies, in which the majority of samples were tested in rural villages soon after collection, 3728 samples were tested. All samples were also examined by microscopy using formol ether concentration and individuals questioned to determine whether they were aware of being infected. After the initial diagnostic work individuals were treated with taeniacidal drugs for worm recovery. Use of the coproantigen test significantly increased the number of cases diagnosed. Of the 41 cases diagnosed by the three diagnostic techniques combined 31 were detected by the dipstick assay making it the most sensitive technique employed. The specificity of the dipstick assay was 99.9% with a positive predictive value of 88.6%. The combined diagnostic approach did not, however, diagnose all cases. The coproantigen test was fast and easy to use. Further improvements may make the dipstick test suitable for wide-scale use in field studies and diagnostic laboratories.

Community prevalence study of taeniasis and cysticercosis in Bali, Indonesia

Summary Taenia solium, a human cestode parasite endemic throughout most of South‐east Asia, causes a number of public health and economic problems. The parasite is endemic in Bali due to a mix of cultural and religious practices. Immunoepidemiological investigation of three rural communities revealed a taeniasis prevalence of 0.72% (3/415). One of the three cases was due to Taenia solium, the other two to Taenia saginata. A further nine cases of Taenia infection were identified from patients from villages surrounding the chosen communities, suggesting that prevalence levels may be higher in other areas. Seroprevalence of human cysticercosis by immunoblot was 1.65% (6/363), though all cases were detected within a single community (6/115; prevalence 5.22%). Several other cases of subcutaneous cysticercosis were identified from local clinics, suggesting continued transmission of Taenia solium in the region. Other intestinal helminth parasites identified within the communities were Ascaris lumbricoides (29.9%), Trichuris trichiuria (33.9%) and hookworm (8.2%).

Detection of Taenia solium Taeniasis Coproantigen Is an Early Indicator of Treatment Failure for Taeniasis

ABSTRACT 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.