• View in gallery

    Individual immune response kinetics of patients with a, multiple cysts (n = 7), b, a single cyst (n = 6), or c, hydrocephalus (n = 3). The kinetics of positive households (n = 6) is shown in d.

  • View in gallery

    Recognition frequency of Taenia solium-specific glycoproteins by the serum of patients with neurocysticercosis (ICs) and seropositive households (HHs). Statistically significant differences between the groups were found for GP 39-42 (P < 0.001) and GP24 (P < 0.045). The numbers above each group of bars is the frequency of recognition by the subgroup of IC with single cyst.

  • 1

    Schantz PM, Sarti E, Plancarte A, Wilson M, Criales JL, Roberts J, Flisser A, 1994. Community-based epidemiological investigations of cysticercosis due to Taenia solium: comparison of serological screening tests and clinical findings in two populations in Mexico. Clin Infect Dis 18 :879–885.

    • Search Google Scholar
    • Export Citation
  • 2

    Kojic EM, White AC Jr, 2003. A positive enzyme-linked immunoelectrotransfer blot assay result for a patient without evidence of cysticercosis. Clin Infect Dis 36 :7–9.

    • Search Google Scholar
    • Export Citation
  • 3

    Mitchell GF, 1982. Genetic variation in resistance of mice of Taenia taeniaeformis: analysis of host-protective immunity and immune evasion. Flisser A, Willms K, Laclette JP, Larralde C, Ridaura C, Beltrán F, eds. Cysticercosis: Present State of Knowledge and Perspectives. New York: Academic Press, 575–584.

  • 4

    Williams JF, Engelkirk PG, Lindsay MC, 1982. Mechanisms of immunity in rodent cysticercosis. Flisser A, Willms K, Laclette JP, Larralde C, Ridaura C, Beltrán F, eds. Cysticercosis: Present State of Knowledge and Perspectives. New York: Academic Press, 621–632.

  • 5

    García HH, González AE, Gilman RH, Palacios LG, Jimenez I, Rodriguez S, Verastegui M, Wilkins P, Tsang VCW, 2001. Short report: transient antibody response in Taenia solium infection in field conditions - a major contributor to high sero-prevalence. Am J Trop Med Hyg 65 :31–32.

    • Search Google Scholar
    • Export Citation
  • 6

    Del Brutto OH, Rajshekhar V, White AC, Tsang VCW, Nash TE, Takayanagui OM, Schantz PM, Evans CAW, Flisser A, Correa D, Botero D, Allan JC, Sarti E, Gonzalez AE, Gilman RH, García HH, 2001. Proposed diagnostic criteria for neurocysticercosis. Neurology 57 :177–183.

    • Search Google Scholar
    • Export Citation
  • 7

    García H, Evans CAW, Nash TE, Takayanagui OM, White AC, Botero D, Rajshekhar V, Tsang VCW, Schantz PM, Allan JC, Flisser A, Correa D, Sarti E, Friedland JS, Martinez SM, Gonzalez A, Gilman RH, Del Bruto O, 2002. Current consensus guidelines for treatment of neurocysticercosis. Clin Micro-biol Rev 15 :747–756.

    • Search Google Scholar
    • Export Citation
  • 8

    Tsang VCW, Brand J, Boyer E, 1989. Enzyme-linked immunoelectrotransfer blot assay and glycoprotein antigens for diagnosing human cysticercosis. J Infect Dis 159 :50–59.

    • Search Google Scholar
    • Export Citation
  • 9

    Allan JC, Avila G, García-Noval J, Flisser A, Craig PS, 1990. Immunodiagnosis of taeniasis by coproantigen detection. Parasitology 101 :473–477.

    • Search Google Scholar
    • Export Citation
  • 10

    Wilson MR, Bryan RT, Fried JA, Ware DA, Schantz PM, Pilcher JB, Tsang VCW, 1991. Clinical evaluation of the cysticercosis enzyme-linked immunoelectro-transfer blot in patients with neurocysticercosis. J Infect Dis 164 :1007–1009.

    • Search Google Scholar
    • Export Citation
  • 11

    Proaño-Narváez JV, Meza-Lucas A, Mata-Ruiz O, García-Jerónimo RC, Correa D, 2002. Laboratory diagnosis of human neurocysticercosis: double blind comparison of ELISA and EITB. J Clin Microbiol 40 :2115–2118.

    • Search Google Scholar
    • Export Citation
  • 12

    Bern C, Garcia HH, Evans C, González AE, Verastegui M, Tsang VCW, Gilman RH, 1999. Magnitude of the disease burden from neurocysticercosis in a developing country. Clin Infect Dis 29 :1203–1209.

    • Search Google Scholar
    • Export Citation
  • 13

    Theis JH, Goldsmith RS, Flisser A, Koss J, Chioino C, Plancarte A, Segura A, Widjana D, Sutisna P, 1994. Detection by immunoblot assay of antibodies to Taenia solium cysticerci in sera from residents of rural communities and from epileptic patients in Bali, Indonesia. Southeast Asian J Trop Med Public Health 25 :464–468.

    • Search Google Scholar
    • Export Citation
  • 14

    García HH, Gilman RH, Catacora M, Verastegui M, González AE, Tsang VCW, 1997. Serologic evolution on neurocysticercosis patients after antiparasitic therapy. J Infect Dis 175 :486–489.

    • Search Google Scholar
    • Export Citation
  • 15

    Ito A, Nakao M, Ito Y, Yuzawa I, Morishima H, Kawano N, Fijii K, 1999. Neurocysticercosis case with a single cyst in the brain showing dramatic drop in specific antibody titers within 1 year after curative surgical resection. Parasitol Int 48 :95–99.

    • Search Google Scholar
    • Export Citation

 

 

 

SHORT REPORT: LIMITED AND SHORT-LASTING HUMORAL RESPONSE IN TAENIA SOLIUM: SEROPOSITIVE HOUSEHOLDS COMPARED WITH PATIENTS WITH NEUROCYSTICERCOSIS

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  • 1 Instituto de Diagnóstico y Referencia Epidemiológicos, Secretaría de Salud, Mexico City, Mexico; Hospital Regional de Zona No. 25, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, Mexico

Epidemiologic data suggest that 30–40% of Taenia solium-seropositive people become spontaneously negative without acquiring cysticercosis. To compare the responses of these individuals with those of patients with neurocysticercosis, we screened seropositive persons among family members of 16 patients. We searched for specific antibodies in patients and their 118 households by an enzyme-linked immunoelectrotransfer blot assay using specific glycoproteins of T. solium metacestodes. We found six seropositive individuals without neurocysticercosis among members of four families. The matching patients were young, harbored viable cysts, and had short evolution of disease. The baseline response of healthy seropositive individuals was scarce and showed a low frequency of antibodies against glycoproteins GP39-42 and GP24, which are immunodominant in patients with neurocysticercosis. Moreover, they became spontaneously negative in few months. The response of patients was heterogeneous as shown in other studies. The results of this work support a highly dynamic host-parasite immunologic interaction and suggest individual susceptibility or level of exposure among family members.

Epidemiologic data have shown that only one-third of Taenia solium-seropositive individuals harbor cysts within the brain.1 Although false-positive results may explain some of these cases,2 they could also be clinically silent cysticercosis cases or people who spontaneously resolved or even avoided infestation. Evidence supporting these possibilities in human and animal cysticercosis has been published.3–5

In this study, we report preliminary data obtained from 118 households of 16 consecutive index cases (ICs) of neurocysticercosis (Table 1). The study was conducted after protocol review and approval by the Ethics Committee of the Instituto Mexicano del Seguro Social, where the patients where diagnosed on the basis of consensus criteria.6 Only cases with active or mixed forms of cysticercosis were included; most presented either single or multiple cysts, with or without ring-like enhancement. Cases with hydrocephalus alone or combined with cysts or with cysts and calcifications were also included. Patients received individualized therapy depending on clinical, immunologic, and imaging baseline data (computed tomography [CT] and magnetic resonance imaging [MRI]), as well as on response to treatment.7 Three patients became negative both by imaging and serologically without cestocidal treatment, while three others harboring a single lesion required one or two regimens at standard doses: prazi-quantel, 50 mg/kg for 15 days or albendazole, 15 mg/kg for 15 days, with concomitant steroid or anti-epileptic drugs (Table 1). Three cases with hydrocephalus also required a ventricle-peritoneum shunt. Clinical status was evaluated before, during, and after treatment; the therapeutic response was verified periodically by neuroimaging. When the lesions disappeared or the hydrocephalus resolved, it was considered that the patient showed imaging cure. After signed consent was obtained, blood samples where drawn from all ICs and households and specific antibodies against T. solium cysticercus-specific glycoproteins were detected in their serum by an enzyme-linked immunoelectrotransfer blot (EITB) assay.8 Antigen detection in fecal samples by an enzyme-linked immunosorbent assay (ELISA) was used to locate adult parasite carriers.9 This was an antigen-capture ELISA for saline supernatants of fecal samples. The capture antibody was the IgG fraction of a hyperimmune rabbit serum produced against a somatic extract of taeniid proglottids. A peroxidase-conjugated fraction of the same IgG was used as the secondary antibody. Neuroimage studies were performed in households positive for serum antibodies or coproantigens. More serum samples were obtained from all ICs during and after treatment every time they presented for clinical or imaging follow-up. Positive households were followed until negative results were obtained. Data were analyzed by the SigmaStat 4.0 software (Jandel Scientific, San Rafael, CA). Chi-square or Fischer exact tests were used to determine statistical significance of proportions differences. The Student’s t-test was used to compare quantitative variables with normal distributions. Differences were considered to be statistically significant when P ≤ 0.05.

Global findings of patients with neurocysticercosis included in the present work are shown in Table 1, which is arbitrarily divided in two subgroups, based on time of imaging and EITB assay result conversion. Most cases in the subgroup that resolved their disease in less than 17 months were male, harbored a single cyst, presented short evolution time of symptoms, and needed few or no cestocidal treatment courses to obtain imaging cure. All these features were significantly different from those of the second group. Conversely, age was significantly related to mixed or complicated disease forms, i.e., five of six patients less than 26 years old presented with a single cyst without complications, while 9 of 10 cases more than 25 years old were harboring multiple cysts or developed hydrocephalus (P = 0.007, by Fisher’s exact test). Seizures alone (75%) or combined with headache (12.5%) were the most frequent clinical findings. One asymptomatic case (IC8) was detected because he was diagnosed as a carrier of an adult T. solium tapeworms by a coproantigen-ELISA, but multiple cysticerci were observed in his brain by MRI. All patients with neurocysticercosis and six households who belonged to four different families had antibodies against T. solium-specific glycoproteins. These households were relatives of the IC with less than three months of clinical evolution, resolved the cystic lesions at a maximum of one year, and became seronegative in less than 17 months (Table 1). The baseline number of EITB assay bands was greater and the response decay time was longer in cases with multiple cysts or complicated forms of the disease compared with those with a single cyst or the households (Figure 1). The response pattern of the IC group resembled that reported in other studies, i.e., with an immunodominance of glycoproteins GP39-42 and GP-24, followed by GP50, GP21, and GP13 (Figure 2).8,10,11 Patients with a single cyst also showed pattern (values above bars in Figure 2).10,11 A lower frequency of glycoproteins GP39-42, GP-24, and GP13 was observed in the serum samples of seropositive households compared with the IC, with GP50 being more frequent. In the comparison with the pattern of bands recognized by seropositive households with that of their corresponding IC (Table 2), three of four ICs showed the known immunodominant GPs or a combination of them, but it was also noteworthy that all reacted to GP50. Moreover, IC5, a seven-year-old child, had antibodies only to GP50. Seropositive households showed a heterogeneous response in comparison to ICs, with a remarkably low frequency of GP 39–42.

Previous studies have shown a high prevalence of specific antibodies against T. solium metacestodes in healthy people in endemic regions.1,12,13 However, less than one-third of them harbor parasites in the brain, as assessed by CT scans.1 Moreover, it has been observed that approximately 40% of seropositive individuals become spontaneously negative in 1–3 years.5 Studies in rodents experimentally infected with Taenia spp. eggs have demonstrated a genetically based resistance to infection, at least partially due to a rapid synthesis of specific antibodies against the oncospheres, which develop before the immune evasion mechanisms of the parasite are activated.3 Six seropositive households of ICs were found in this study among short-time evolution IC families and none had cases with long-lasting disease. This could be due to the fast spontaneous decrease of antibodies in exposed but non-infected households. Thus, the dynamics of the humoral response against T. solium is quite rapid in individuals who are exposed and either avoid parasite establishment or spontaneously resolve an infestation. In this regard, it is interesting that imaging cure after chemotherapy or surgical subtraction of cyst is followed by a rapid decrease in antibodies (Table 1).14,15 Conversely, GP39-42 was hardly recognized by baseline antibodies of households and GP24 was observed at a low frequency. More studies are needed to determine if GP39-42 is an antigen expressed later during oncosphere development. If so, it might be a marker for establishment of cysticerci, and could be useful in epidemiologic studies to distinguish between persons with cysticercosis and those exposed to the parasite but not infested.

The results of this work suggest individual susceptibility to infection by T. solium or different levels of exposure within families and a fast host-parasite immunologic interaction, which either resolves in few months or it is established as a long-lasting relationship.

Table 1

Clinical, imaging, and antibody response data of index cases with neurocysticercosis*

IC/No. of HHsSex†Age (years)Number of seropositive householdsNumber and type of lesions†Evolution time of clinical symptoms (months)‡Number of cestocidal treatments‡Other treatmentsTime for conversion (months):
HeadacheSeizuresSteroidAnti-epilepticImaging‡ cureSeronegative resultBoth
* IC = index case; HHs = households; SC-E = single cyst with enhancement; SC-NE = single cyst without enhancement; MC = multiple cysts; s/c = proportion of cases with a single cyst/those with multiple cysts or complicated forms; Hy = hydrocephalus; MCa = multiple calcifications.
†The frequency of seropositive households and of simple forms of disease was significantly different between the upper and lower groups (P = 0.038 and P = 0.0034, respectively, by Fisher’s exact test).
‡Evolution time of seizures, number of cestocidal treatments, and months of imaging cure were significantly different between the upper and lower groups (P < 0.022, P = 0.013, respectively, by Student’s t-test).
§ Since the last image showed cortical atrophy and multiple calcifications, she was considered cured in relation to the presence of living parasites. Eleven months later, the case became seronegative, but it was necessary to change her ventriculo-peritoneal shunt.
1/7M222 (29%)SC-E31YesYes459
2/4M110SC-NE21YesYes718
3/8F150SC-E40YesYes7310
4/7M430SC-NE20NoYes7310
5/7M72 (29%)SC-E10NoYes7411
6/4M400MC522NoYes12214
7/11F251 (9%)SC-E22YesYes12416
8/11M281 (9%)MC01NoNo12416
HHs total n = 59M/F = 6/2Mean = 24+HHs = 6/8s/c = 6/8Mean = 2.0Mean = 0.94/87/8Mean = 8.5Mean = 3.3Mean = 11.8
9/9M270Hy843YesYes121123
10/7F440Hy + SC + MCa12YesYes201434
11/9F620MC96963NoYes361046
12/9F290MC31YesYes14Unresolved
13/5F400MC482NoYes22Unresolved
14/4F130MC62YesYes25Unresolved
15/8M300MC1443YesYesUnresolvedUnresolved
16/8F670Hy + SC24481YesYesUnresolvedUnresolved§
HHs total n = 59M/F = 2/6Mean = 39+HHs = 0/8s/c = 0/8Mean = 53.6Mean = 2.16/88/8Mean = 23.4Mean = 11.7>23
Table 2

Comparison of baseline glycoprotein (GP) recognition patterns by the seropositive households (HHs) and the corresponding index cases (ICs) with neurocysticercosis*

Glycoprotein recognized
PersonAge/sexCT findings in ICGP50GP39–42GP24GP21GP18GP14GP13
* Age is in years. CT = computed tomography; SC-E = single cyst with enhancement; Neg = negative; MC = multiple cyst.
†Patient with taeniasis and cysticercosis.
IC 122/MSC-E++++
HH120/FNeg++
HH230/MNeg++
IC 57/MSC-E+
HH 127/FNeg+++
HH 211/MNeg+++
IC 725/FSC-E++++++
HH 130/FNeg+++
IC 8†28/MMC++++
HH 140/FNeg+
Total Ics3M/1F3SC-E/1MC4 (100%)3 (75%)3 (75%)2 (50%)0 (0%)1 (25%)2 (50%)
Total HHs2M/4F6 Neg3 (50%)1 (17%)3 (50%)3 (50%)1 (17%)1 (17%)1 (17%)
Figure 1.
Figure 1.

Individual immune response kinetics of patients with a, multiple cysts (n = 7), b, a single cyst (n = 6), or c, hydrocephalus (n = 3). The kinetics of positive households (n = 6) is shown in d.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 69, 2; 10.4269/ajtmh.2003.69.223

Figure 2.
Figure 2.

Recognition frequency of Taenia solium-specific glycoproteins by the serum of patients with neurocysticercosis (ICs) and seropositive households (HHs). Statistically significant differences between the groups were found for GP 39-42 (P < 0.001) and GP24 (P < 0.045). The numbers above each group of bars is the frequency of recognition by the subgroup of IC with single cyst.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 69, 2; 10.4269/ajtmh.2003.69.223

Authors’ addresses: Antonio Meza-Lucas and Roberto C. García-Jerónimo, Instituto de Diagnóstico y Referencia Epidemiológicos, SSA, Carpio 470, Col. Sto. Tomás, Mexico City 11340, DF, Mexico, Telephone: 52-55-5341-4880/4760/4953, extension 260. Laura Carmona-Miranda, Alejandra Torrero-Miranda, Germán González-Hidalgo, and Guillermo López-Castellanos, Hospital General Regional No. 25, Calz. Ignacio Zaragoza 1840, Col. Juan Escutia, México City 09100, DF, Mexico, Telephone: 52-55-5745-6508/6282/6391/6532. Dolores Correa, 8° Piso, Torre de Investigación, Instituto Nacional de Pediatría, SSA, Av Insurgentes Sur 3700-C, Col. Insurgentes-Cuicuilco, Mexico City, 04530, DF, Mexico, Telephone: 52-55-5606-7223 or 5606-0002, extensions 455 or 458, Fax: 52-55- 5606-9455, E-mail: [email protected] or [email protected].

Acknowledgments: We thank Dr. Victor C. W. Tsang and his group at the Centers for Disease Control and Prevention (Atlanta, GA) for training in the isolation of Taenia solium glycoprotein and for quality monitoring of EITB strips and control serum samples.

REFERENCES

  • 1

    Schantz PM, Sarti E, Plancarte A, Wilson M, Criales JL, Roberts J, Flisser A, 1994. Community-based epidemiological investigations of cysticercosis due to Taenia solium: comparison of serological screening tests and clinical findings in two populations in Mexico. Clin Infect Dis 18 :879–885.

    • Search Google Scholar
    • Export Citation
  • 2

    Kojic EM, White AC Jr, 2003. A positive enzyme-linked immunoelectrotransfer blot assay result for a patient without evidence of cysticercosis. Clin Infect Dis 36 :7–9.

    • Search Google Scholar
    • Export Citation
  • 3

    Mitchell GF, 1982. Genetic variation in resistance of mice of Taenia taeniaeformis: analysis of host-protective immunity and immune evasion. Flisser A, Willms K, Laclette JP, Larralde C, Ridaura C, Beltrán F, eds. Cysticercosis: Present State of Knowledge and Perspectives. New York: Academic Press, 575–584.

  • 4

    Williams JF, Engelkirk PG, Lindsay MC, 1982. Mechanisms of immunity in rodent cysticercosis. Flisser A, Willms K, Laclette JP, Larralde C, Ridaura C, Beltrán F, eds. Cysticercosis: Present State of Knowledge and Perspectives. New York: Academic Press, 621–632.

  • 5

    García HH, González AE, Gilman RH, Palacios LG, Jimenez I, Rodriguez S, Verastegui M, Wilkins P, Tsang VCW, 2001. Short report: transient antibody response in Taenia solium infection in field conditions - a major contributor to high sero-prevalence. Am J Trop Med Hyg 65 :31–32.

    • Search Google Scholar
    • Export Citation
  • 6

    Del Brutto OH, Rajshekhar V, White AC, Tsang VCW, Nash TE, Takayanagui OM, Schantz PM, Evans CAW, Flisser A, Correa D, Botero D, Allan JC, Sarti E, Gonzalez AE, Gilman RH, García HH, 2001. Proposed diagnostic criteria for neurocysticercosis. Neurology 57 :177–183.

    • Search Google Scholar
    • Export Citation
  • 7

    García H, Evans CAW, Nash TE, Takayanagui OM, White AC, Botero D, Rajshekhar V, Tsang VCW, Schantz PM, Allan JC, Flisser A, Correa D, Sarti E, Friedland JS, Martinez SM, Gonzalez A, Gilman RH, Del Bruto O, 2002. Current consensus guidelines for treatment of neurocysticercosis. Clin Micro-biol Rev 15 :747–756.

    • Search Google Scholar
    • Export Citation
  • 8

    Tsang VCW, Brand J, Boyer E, 1989. Enzyme-linked immunoelectrotransfer blot assay and glycoprotein antigens for diagnosing human cysticercosis. J Infect Dis 159 :50–59.

    • Search Google Scholar
    • Export Citation
  • 9

    Allan JC, Avila G, García-Noval J, Flisser A, Craig PS, 1990. Immunodiagnosis of taeniasis by coproantigen detection. Parasitology 101 :473–477.

    • Search Google Scholar
    • Export Citation
  • 10

    Wilson MR, Bryan RT, Fried JA, Ware DA, Schantz PM, Pilcher JB, Tsang VCW, 1991. Clinical evaluation of the cysticercosis enzyme-linked immunoelectro-transfer blot in patients with neurocysticercosis. J Infect Dis 164 :1007–1009.

    • Search Google Scholar
    • Export Citation
  • 11

    Proaño-Narváez JV, Meza-Lucas A, Mata-Ruiz O, García-Jerónimo RC, Correa D, 2002. Laboratory diagnosis of human neurocysticercosis: double blind comparison of ELISA and EITB. J Clin Microbiol 40 :2115–2118.

    • Search Google Scholar
    • Export Citation
  • 12

    Bern C, Garcia HH, Evans C, González AE, Verastegui M, Tsang VCW, Gilman RH, 1999. Magnitude of the disease burden from neurocysticercosis in a developing country. Clin Infect Dis 29 :1203–1209.

    • Search Google Scholar
    • Export Citation
  • 13

    Theis JH, Goldsmith RS, Flisser A, Koss J, Chioino C, Plancarte A, Segura A, Widjana D, Sutisna P, 1994. Detection by immunoblot assay of antibodies to Taenia solium cysticerci in sera from residents of rural communities and from epileptic patients in Bali, Indonesia. Southeast Asian J Trop Med Public Health 25 :464–468.

    • Search Google Scholar
    • Export Citation
  • 14

    García HH, Gilman RH, Catacora M, Verastegui M, González AE, Tsang VCW, 1997. Serologic evolution on neurocysticercosis patients after antiparasitic therapy. J Infect Dis 175 :486–489.

    • Search Google Scholar
    • Export Citation
  • 15

    Ito A, Nakao M, Ito Y, Yuzawa I, Morishima H, Kawano N, Fijii K, 1999. Neurocysticercosis case with a single cyst in the brain showing dramatic drop in specific antibody titers within 1 year after curative surgical resection. Parasitol Int 48 :95–99.

    • Search Google Scholar
    • Export Citation

Author Notes

Reprint requests: Dolores Correa, 8° Piso, Torre de Investigación, Instituto Nacional de Pediatría, SSA, Av Insurgentes Sur 3700-C, Col. Insurgentes-Cuicuilco, Mexico City, 04530, DF, Mexico.
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