Journal of the Neurological Sciences 262 (2007) 153–157www.elsevier.com/locate/jns

Strategies for the elimination of taeniasis/cysticercosis

Héctor H. García a,b,c,e,⁎, Armando E. González b,d,e, Oscar H. Del Brutto f,Victor C.W. Tsang b,e,g, Fernando Llanos-Zavalaga b,h, Guillermo Gonzalvez b,

Jaime Romero b, Robert H. Gilman a,b,e

for The Cysticercosis Working Group in PeruaDepartment of Microbiology, School of Sciences, Universidad Peruana Cayetano Heredia, Lima, Peru

b Proyecto de Eliminacion de Cisticercosis, Universidad Peruana Cayetano Heredia, Lima, PerucCysticercosis Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru

d School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, PerueDepartment of International Health, Johns Hopkins University Bloomberg School of Hygiene and Public Health, Baltimore, MD, USA

fHospital-Clinica Kennedy, Guayaquil, Ecuadorg Parasitic Diseases Branch, Division of Parasitic Diseases, National Centers for Infectious Diseases, Centers for Disease Control and Prevention, USA

h School of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, Peru

Available online 2 August 2007

Abstract

Advances in the field of neurocysticercosis continue to shape our understanding of the disease and our efforts to control it. Several attemptshave been made to eradicate the disease with active interventions such as changing domestic pig-raising practices, mass chemotherapy ofporcine cysticercosis and taeniasis, selective detection and treatment of taeniasis, and community health education. Moreover, ongoing progressin the diagnosis of taeniasis and the development of a porcine vaccine against cysticercosis in Australia, Mexico and Peru has yielded at least oneeffective vaccine that is currently available. Thus far, however, attempted interventions have only been successful in temporarily disruptingtransmission of the disease. Controlled data on the efficacy and acceptability of the different interventions is urgently needed to provide a base-line schematic for intervention which could later be tailored to each particular endemic scenario.© 2007 Published by Elsevier B.V.

Keywords: Taeniasis; Cysticercosis; Computed tomography

1. Introduction

Taenia solium taeniasis/cysticercosis is widely endemic inmost developing countries, where it accounts for approxi-mately one-third of all seizure and epilepsy cases [1–3].Several recent studies using computed tomography (CT) inrural villages in Guatemala, Mexico, Ecuador and Hondurashave revealed that up to 20% of the general population inthese villages have asymptomatic brain calcifications [1–6],suggesting that patients who present for medical attentionwith symptomatic neurocysticercosis merely represent thetip of the clinical iceberg. Seroepidemiological data, in

⁎ Corresponding author. Department of Microbiology, School of Sciences,Universidad Peruana Cayetano Heredia, Lima, Peru.

E-mail address: HGARCIA@TERRA.COM.PE (H.H. García).

0022-510X/$ - see front matter © 2007 Published by Elsevier B.V.doi:10.1016/j.jns.2007.06.039

conjunction with the above described population-basedneuroimaging studies, also indicate that the clinical icebergmay be more varied than originally perceived.

In recent years, new diagnostic tools for the diagnosis ofhuman taeniasis [7–9], human neurocysticercosis [10–13],and porcine cysticercosis[14] have been developed, as wellas promising pig vaccines [15–17], and single dose anti-parasitic treatment of infected pigs [18–20]. GPS/GIS dataand mathematical modeling have provided additionalpowerful analytical tools to further elucidate the dynamicsof this disease complex. All these advancements in thediagnostic assays, clinical aspects, and epidemiology oftaeniasis and neurocysticercosis have enriched our under-standing of the evolution of infection and disease and makeus believe that, as suggested 15 years ago [21], elimination ofthis infection is possible.

Fig. 1. Brain CT scan showing multiple neurocysticercosis lesions in diversestages.

154 H.H. García et al. / Journal of the Neurological Sciences 262 (2007) 153–157

2. Why should we attempt to eliminate T. solium?

2.1. Burden of disease

The magnitude of the disease burden associated withneurocysticercosis in endemic countries is enormous.Neurocysticercosis is generally accepted as the singlegreatest cause of acquired epilepsy in developing countries,and recent controlled studies using CT in Honduras, Ecuadorand Peru have demonstrated a solid association betweenneurocysticercosis and seizures in the field, with nearly 30%of seizures attributable to neurocysticercosis infection [1–4].Seroprevalence rates can reach up to 25% in generalpopulations found in endemic areas [22]. An estimated 75million individuals in Latin America alone inhabit endemicregions, 400,000 of whom are afflicted with symptomaticdisease [23]. Beyond the borders of endemic countries,neurocysticercosis is increasingly recognized as a cause ofseizures in the developed world, primarily in immigrants andindividuals who have traveled to endemic areas [24–26].

2.2. Potential for elimination

Cysticercosis is assumed to be eradicable on the basis ofseveral characteristics: humans are the only definitive hostand sole source of infection for intermediate hosts; easilycontrollable domestic animals as primary intermediate hostsor reservoirs; lack of important wild life as reservoirs; andavailability of interventions for control [21] (Table 1).

3. Key problems in diagnosis and control

3.1. Diagnosis of human cysticercosis in the field

The diagnosis of neurocysticercosis at population levelcan represent an even greater challenge than diagnosis on acase by case hospital basis. Neither neuroimaging studies,serological assays, nor the two tests used in combinationare capable of detecting every case of neurocysticercosis.

Table 1Currently available tools

DiagnosticsSerology – Antibody tests for cysticercosis [10,11,14]

– Antigen detection tests for cysticercosis[12,13]– Antibody tests for taeniasis [8,9]

Stool microscopyStool tapeworm antigen detection [7]

Mass chemotherapy – Niclosamide (humans)– Praziquantel (humans) a

– Oxfendazole (pigs)[18–20]Vaccine candidates

[15–17]Analytical tools – GPS/GIS, spatial analysis

– Mathematical modelinga One case of neurological symptoms after deworming with 10 mg/k of

praziquantel has been reported [27].

Currently, the enzyme-linked immunelectro-transfer blotassay (EITB) is the most feasible screening tool for use on anepidemiological level [22]. However, as the sensitivity ofEITB is significantly lower in patients with only a single cystor only calcified lesions, the use of this assay alone as ascreening tool may miss a sizeable cohort of individuals withactive symptomatology who fall into either of these twocategories. Moreover, seronegative individuals with positiveCT imaging but no neurological evidence of the disease maysimply have asymptomatic infection, or may have falsepositive neuroimaging due to an unrelated lesion. Initialseroepidemiological data have revealed strikingly highseroprevalences of antibodies to T. solium. Interestingly,however, the association between seropositivity and sei-zures, although consistent, is considerably weaker thanexpected (odds ratio 2–3) [2,28,29]. Furthermore, seroepi-demiological data and population-based neuroimagingstudies have identified a group of seropositive individualswithout evidence of neurological disease by symptomatol-ogy or CT imaging, calling into question the commonly heldmisconception that most, if not all, cysticercosis infectionsattack the central nervous system. Seropositivity withoutevidence of neurological disease may indicate sub-clinicalinfection, cysticercosis outside of the CNS, or successfuldevelopment of protective immunity. Similarly, pigs withviable infections exhibit strong serological reactions, whileconversely, only one-third of seropositive pigs contain evi-dence of viable infection in their carcasses. Of these, lessthan half have neurological evidence of disease. Therefore,the detection of antibodies by no means equates with viableinfection or neurological disease (Fig. 1).

155H.H. García et al. / Journal of the Neurological Sciences 262 (2007) 153–157

3.2. Diagnosis of human taeniasis in the field

The prevalence of human taeniasis even in endemic areas,is usually below 2% [28,29]. This means that an assay with aspecificity of 98% will detect at least as many true positivesas false positives, duplicating treatment efforts or leading to asecond diagnostic assay.

Also, villagers in many places are reluctant to collect stoolsamples due to hygienic reasons or cultural beliefs. Even if asample is collected, the delay between sample collection anddiagnosis will cause that some individuals with taeniasis willnot come back for their results thus leading to increasedefforts to find and treat them.

3.3. Diagnosis of porcine cysticercosis in the field

Tongue examination is widely used by villagers and leadsto the admission of sizable amounts of infested pork in thehuman food chain, mostly presented as clean pork. Immu-nological assays collide with the fact that, as per humancysticercosis, there are many times more antibody-positivepigs than pigs harboring cysts, thus the positive predictivevalue of these assays is low.

3.4. Economic factors

Taeniasis/cysticercosis is a disease of poverty. Villagersraise pigs because of economic reasons, allow them to roamfreely for the same economic reasons, and will not invest inimmunizing their pigs or treat their pigs because of economics.The best demonstration of this is hog cholera — this diseasehas a lethality of approximately 30% and there is an availablevaccine that costs less than US$ 0.50 per animal; nevertheless,villagers will not spend their money or time to immunize theiranimals.

3.5. Migration

Villagers do not always stay in their towns. According toseason, harvest time, or routine activities (school, work, etc)there is continuous migration between villages, mostly to-wards bigger towns. Pigs are also commonly bought andtransported to different towns.

4. Previous control experiences

4.1. Improving living conditions

T. solium was eliminated from most of Europe during the19th and early 20th centuries. Presumably several factorsthat included improvements in sanitation, education, andcommercial pig production contributed to the elimination ofdisease in these areas. However, other countries whichexperienced similar overall development remained endemic.As much as it can be judged by the European experience, thesustainability of this measure is almost absolute.

4.2. Slaughterhouse control

Slaughterhouse control is suggested as a key control com-ponent by some agencies. However, this control measure ismostly ineffective, particularly if we take into account thatmost infected pigs in the field harbor a few cysts that willsurely be missed by routine carcass examination. Even worse,the local detection of infected animals in rural endemic villagesby examination of the tongue of the pig [30] leads to thedevelopment and establishment of illegal markets for infectedpork. To avoid confiscation, peasants will not take theirtongue-positive animals to the formal slaughterhouse.

4.3. Mass human chemotherapy

This has been tested in several countries includingEcuador [31], Mexico [32,33], Guatemala [34], and Peru[35]. In general the result was a decrease in prevalence ofporcine chemotherapy and human taeniasis. While there isscarce data available on sustainability, results seem tosuggest that transmission variables will return to pre-intervention levels a few months after chemotherapy roundsare interrupted. Verbal data from Ecuador referred return tobaseline levels after 3 years. In Peru disease incidencerecrudesced in less than 1 year [35].

4.4. Immunotherapy

In 1993, Molinari et al. [36,37] proposed to inject pigswith cysticercus antigens to boost their immune response tothe parasite and eliminate established cysts. Data showingpositive, albeit partial effects of this method were obtainedby two field studies. More recently, a vaccine made withsynthetic peptides derived from another parasite (Taeniacrassiceps) has been claimed to have a similar effect [38].

4.5. Health education

Health education of the target population should beincluded in the design of control/elimination programs forseveral reasons, including increased sustainability of theprogram along time. Health education alone was tested in aMexican study comparing Health Education, Human Masschemotherapy, and both. The study showed decreasedtransmission in the village allocated to Education, but therewas only a minor effect in the village receiving healtheducation plus praziquantel [39].

4.6. Pig corralling

Intuitively the simplest way to eliminate transmissionwould be to corral pigs to prevent their contact with humanstools. However, one of the reasons why rural villagers indeveloping countries raise pigs is precisely that by allowingpigs to roam free, the owner does not need to investin feeding them. This practice is crucial in subsistence

Fig. 2. Treatment of pigs with oxfendazole during an intervention inTumbes, Peru.

156 H.H. García et al. / Journal of the Neurological Sciences 262 (2007) 153–157

economies where the pigs frequently represent a key cashincome and are bought or sold according to the economicalsituation of the owners.

4.7. Treatment of pigs with oxfendazole

Oxfendazole when given as a single dose at 30 mg/k killsall cysts in the pig's muscles. Some cysts may survive in thebrain of the animal, although this should have minimalimpact in transmission. The major drawback of using OFZ asa control measure is the delay between drug therapy andcomplete disappearance of cyst remnants (it takes 3 monthsfor the pork to look completely clean) [18–20] (Fig. 2).

4.8. Pig vaccine

Lightowlers et al. [15,16,40] have obtained close to 100%protection when using a vaccine against T. solium in pigs.Currently the vaccine requires at least two doses to beeffective. Other vaccine candidates include a T. crassicepsvaccine [17,38] and DNA immunization [41,42].

4.9. Meat processing

Cyst die if meat is frozen at 4 °C for more than 1 month[43], or − 20 °C for one to 3 days [44]. The use of gamma-radiation has also been proposed [45]. Feasibility of theseinterventions at the rural level, however, is minimal.

5. The current elimination program in northern Peru

Presently, a large scale eradication effort on the Northerncoast of Peru, funded by the Bill and Melinda GatesFoundation, is in progress, exploring selected combinationsof these measures to control or eliminate the disease. Thecontrol activities have already been applied in rural areaswith approximately 20,000 inhabitants, and data from apopulation of over 50,000 have already been collected andentered in a multi-level relational data system including dataon GPS house coordinates (the interventions will be scaled toreach total target population, 100,000 inhabitants, by early2008). A second comparison round to be applied during2007 should provide data on efficacy, cost and acceptabilityof two pre-selected combinations of interventions, includingthe use of a pig vaccine in field conditions.

Acknowledgments

Research grants from the Wellcome Trust; The Bill andMelinda Gates Foundation, and from the National Instituteof Allergy and Infectious Diseases, and the National Instituteof Neurological Diseases and Stroke, NIH, USA, supportother research by the authors. The sponsors had no role in thedesign or performance of this paper.

References

[1] Garcia HH, Del Brutto OH. Neurocysticercosis: updated conceptsabout an old disease. Lancet Neurol 2005;4(10):653–61.

[2] Montano SM, Villaran MV, Ylquimiche L, et al. Neurocysticercosis:association between seizures, serology, and brain CT in rural Peru.Neurology 2005;65(2):229–33.

[3] Del Brutto OH, Santibanez R, Idrovo L, et al. Epilepsy and neuro-cysticercosis in Atahualpa: a door-to-door survey in rural coastalEcuador. Epilepsia 2005;46(4):583–7.

[4] Medina MT, Duron RM, Martinez L, et al. Prevalence, incidence, andetiology of epilepsies in rural Honduras: the Salama Study. Epilepsia2005;46(1):124–31.

[5] Sanchez AL, Lindback J, Schantz PM, et al. A population-based, case-control study of Taenia solium taeniasis and cysticercosis. Ann TropMed Parasitol 1999;93(3):247–58.

[6] Garcia-Noval J, Moreno E, de Mata F, et al. An epidemiological studyof epilepsy and epileptic seizures in two rural Guatemalan commu-nities. Ann Trop Med Parasitol 2001;95(2):167–75.

[7] Allan JC,Wilkins PP, Tsang VC, Craig PS. Immunodiagnostic tools fortaeniasis. Acta Trop 2003;87(1):87–93.

[8] Wilkins PP, Allan JC, Verastegui M, et al. Development of a serologicassay to detect Taenia solium taeniasis. Am J Trop Med Hyg 1999;60(2):199–204.

[9] Levine MZ, Calderon JC, Wilkins PP, et al. Characterization, cloning,and expression of two diagnostic antigens for Taenia solium tapeworminfection. J Parasitol 2004;90(3):631–8.

[10] Hancock K, Pattabhi S, Greene RM, et al. Characterization and cloningof GP50, a Taenia solium antigen diagnostic for cysticercosis. MolBiochem Parasitol 2004;133(1):115–24.

[11] Hancock K, Pattabhi S, Whitfield FW, et al. Characterization andcloning of T24, a Taenia solium antigen diagnostic for cysticercosis.Mol Biochem Parasitol 2006.

[12] Dorny P, Brandt J, Geerts S. Immunodiagnostic approaches fordetecting Taenia solium. Trends Parasitol 2004;20(6):259–60 [authorreply 260-1].

157H.H. García et al. / Journal of the Neurological Sciences 262 (2007) 153–157

[13] Garcia HH, Harrison LJ, Parkhouse RM, et al. A specific antigen-detection ELISA for the diagnosis of human neurocysticercosis. TheCysticercosis Working Group in Peru. Trans R Soc Trop Med Hyg1998;92(4):411–4.

[14] Handali S, Gonzalez AE, Hancock K, et al. Porcine antibody responsesto Taenia solium antigens rGp50 and sTs18var1. Am J Trop Med Hyg2004;71(3):322–6.

[15] Gonzalez AE, Gauci CG, Barber D, et al. Vaccination of pigs to controlhuman neurocysticercosis. Am J Trop Med Hyg 2005;72(6):837–9.

[16] Flisser A, Gauci CG, Zoli A, et al. Induction of protection againstporcine cysticercosis by vaccination with recombinant oncosphereantigens. Infect Immun 2004;72(9):5292–7.

[17] Huerta M, de Aluja AS, Fragoso G, et al. Synthetic peptide vaccineagainst Taenia solium pig cysticercosis: successful vaccination in acontrolled field trial in rural Mexico. Vaccine 2001;20(1-2):262–6.

[18] Gonzales AE, Garcia HH, Gilman RH, et al. Effective, single-dosetreatment or porcine cysticercosis with oxfendazole. Am J Trop MedHyg 1996;54(4):391–4.

[19] Gonzalez AE, Falcon N, Gavidia C, et al. Treatment of porcinecysticercosis with oxfendazole: a dose–response trial. Vet Rec1997;141(16):420–2.

[20] Gonzalez AE, Falcon N, Gavidia C, et al. Time-response curve ofoxfendazole in the treatment of swine cysticercosis. Am J Trop MedHyg 1998;59(5):832–6.

[21] Schantz PM, Cruz M, Sarti E, Pawlowski Z. Potential eradicability oftaeniasis and cysticercosis. Bull Pan Am Health Organ 1993;27(4):397–403.

[22] Tsang V, Wilson M. Taenia solium cysticercosis, an under-recognizedbut serious public health problem. Parasitol Today 1995(11):124–6.

[23] Bern C, Garcia HH, Evans C, et al. Magnitude of the disease burdenfrom neurocysticercosis in a developing country. Clin Infect Dis1999;29(5):1203–9.

[24] Wallin MT, Kurtzke JF. Neurocysticercosis in the United States: reviewof an important emerging infection. Neurology 2004;63(9):1559–64.

[25] Schantz PM, Tsang VC. The US Centers for Disease Control andPrevention (CDC) and research and control of cysticercosis. Acta Trop2003;87(1):161–3.

[26] White Jr AC. Neurocysticercosis: a major cause of neurological diseaseworldwide. Clin Infect Dis 1997;24(2):101–13 [quiz 114-5].

[27] Flisser A, Madrazo I, Plancarte A, et al. Neurological symptoms inoccult neurocysticercosis after single taeniacidal dose of praziquantel.Lancet 1993;342(8873):748.

[28] Schantz PM, Sarti E, Plancarte A, et al. Community-based epidemi-ological investigations of cysticercosis due to Taenia solium: com-parison of serological screening tests and clinical findings in twopopulations in Mexico. Clin Infect Dis 1994;18(6):879–85.

[29] Garcia HH, Gilman RH, Gonzalez AE, et al. Hyperendemic human andporcine Taenia solium infection in Peru. Am J Trop Med Hyg 2003;68(3):268–75.

[30] Gonzalez AE, Cama V, Gilman RH, et al. Prevalence and comparisonof serologic assays, necropsy, and tongue examination for thediagnosis of porcine cysticercosis in Peru. Am J Trop Med Hyg1990;43(2):194–9.

[31] Cruz M, Davis A, Dixon H, Pawlowski ZS, Proano J. Operationalstudies on the control of Taenia solium taeniasis/cysticercosis inEcuador. Bull World Health Organ 1989;67(4):401–7.

[32] Keilbach NM, de Aluja AS, Sarti-Gutierrez E. A programme to controltaeniasis-cysticercosis (T. solium): experiences in a Mexican village.Acta Leiden 1989;57(2):181–9.

[33] Sarti E, Schantz PM,AvilaG, Ambrosio J,Medina-Santillan R, Flisser A.Mass treatment against human taeniasis for the control of cysticercosis: apopulation-based intervention study. TransR SocTropMedHyg 2000;94(1):85–9.

[34] Allan JC, Velasquez-TohomM, Fletes C, et al. Mass chemotherapy forintestinal Taenia solium infection: effect on prevalence in humans andpigs. Trans R Soc Trop Med Hyg 1997;91(5):595–8.

[35] Garcia HH, Gonzalez AE, Gilman RH, et al. Combined human andporcine mass chemotherapy for the control of T. solium. Am J TropMed Hyg 2006;74(5):850–5.

[36] Molinari JL, Rodriguez D, Tato P, Soto R, Arechavaleta F, Solano S.Field trial for reducing porcine Taenia solium cysticercosis in Mexicoby systematic vaccination of pigs. Vet Parasitol 1997;69(1-2):55–63.

[37] Molinari JL, Soto R, Tato P, et al. Immunization against porcinecysticercosis in an endemic area in Mexico: a field and laboratorystudy. Am J Trop Med Hyg 1993;49(4):502–12.

[38] de Aluja AS, Villalobos NM, Nava G, et al. Therapeutic capacity of thesynthetic peptide-based vaccine against Taenia solium cysticercosis inpigs. Vaccine 2005;23(31):4062–9.

[39] Sarti E, Flisser A, Schantz P, Bronfman M, Wijeyaratne P. Interventionstrategies for the prevention and control of Taenia solium taeniosis andcysticercosis in rural areas of Mexico. In: Garcia HH, Martinez SM,editors. Taenia solium Taeniasis/Cysticercosis. Lima: Ed. Universo;1999. p. 327–38.

[40] Lightowlers MW. Vaccination for the prevention of cysticercosis. DevBiol (Basel) 2004;119:361–8.

[41] Wang QM, Sun SH, Hu ZL, Wu D, Wang ZC. Immune response andprotection elicited by DNA immunisation against Taenia cysticercosis.Vaccine 2003;21(15):1672–80.

[42] Guo A, Jin Z, Zheng Y, et al. Induction of protection against porcinecysticercosis in growing pigs by DNA vaccination. Vaccine 2006.

[43] Fan PC, Ma YX, Kuo CH, Chung WC. Survival of Taenia soliumcysticerci in carcasses of pigs kept at 4 C. J Parasitol 1998;84(1):174–5.

[44] Sotelo J, Rosas N, Palencia G. Freezing of infested pork muscle killscysticerci. Jama 1986;256(7):893–4.

[45] Verster A, Du Plessis TA, Van Den Heever LW. The effect of gammaradiation on the cysticerci of Taenia solium. Onderstepoort J Vet Res1976;43(1):23–6.