Neurocysticercosis is an eradicable cause of epilepsy - a plan (and actions) are needed

Between 1930 and 1960, 450 British soldiers who were being assessed for epilepsy and other neurological disease after returning from duty in India were found to be affected by neurocysticercosis (NCC, figure 1), the infection of the human nervous system by the cystic larvae of the pork tapeworm Taenia solium.[1] This unexpectedly frequent finding brought attention to a globally common but yet poorly known disease. Introduction of the CT scan in the 1970’s substantially improved the pre-mortem diagnosis of NCC and slowly began to unveil the scope of the problem. T. solium is now known to be endemic in wide areas of the world including Latin America, Sub-Saharan Africa, Eastern Europe and parts of Asia including the Indian subcontinent, Southeast Asia, and large regions of China.[2] T. solium endemicity is deeply rooted in poverty, and involves domestic pig raising and poor sanitary conditions. As such, the burden of neurologic disease related to continued transmission falls mainly on impoverished rural populations. NCC cases are however diagnosed worldwide even where transmission is not endemic.[2]

Figure 1.

Interventions assessed in the three phases of the Peru Cysticercosis Elimination Program.

NCC may cause focal epilepsy from its lesions, or may lead to distant epileptogenesis through the development of hippocampal sclerosis and subsequent mesial temporal lobe epilepsy. Across all causes of acquired epilepsy (epilepsy not associated to congenital or delivery causes), NCC is likely the most frequent etiology in developing countries. Multiple reviews and metaanalyses consistently calculate approximately 30% of all epilepsies in NCC-endemic regions as attributable to NCC.[3] NCC may, however, manifest as almost any neurological symptom, also frequently including chronic headache, intracranial hypertension, and cognitive impairment.

As far back as 1993, Peter Schantz and colleagues published a landmark paper claiming that T. solium cysticercosis is an eradicable disease.[4] They based their claim on several arguments, namely that, a) humans are the sole definitive host (a condition called taeniasis) and are required to perpetuate the lifecycle, b) practical intervention was available in the form of mass chemotherapy for taeniasis with safe and efficacious drugs, c) risk of exposure of domestic pigs, the only usual intermediary host, can be managed, and d) the absence of a wildlife reservoir. T. solium was formally included in a list of six human diseases targeted for eradication, [5] and in subsequent years, diagnostics for human and pig infection improved, as did therapies to treat taeniasis, porcine cysticercosis, and NCC. The World Health Organization reports that the rate of epilepsy from neurocysticercosis can be reduced by community interventions using different approaches.[6,7]

During 2003 to 2013, we performed a large elimination demonstration program in Tumbes (Northern Coast of Peru) aimed to provide proof of concept that transmission of T. solium can be interrupted on a regional level. The final strategy in this program was a one-year intensive regimen involving three rounds of mass chemotherapy of humans with niclosamide (including systematic post-treatment testing after the first round to rule out treatment failure), five rounds of mass oxfendazole in pigs, and one round (two doses) of the TSOL18 pig cysticercosis vaccine. At the end of the scaled intervention, no new infections were found in pigs in 105 out of 107 villages, providing sound evidence that T. solium transmission can be interrupted by active intervention (Figure 1).[8] We also demonstrated in a subset of villages that Interruption of transmission persisted for one year after stopping the intervention in a significant proportion of intervened villages.

Interrupting transmission on a regional level, however, may be a short-lived triumph without ongoing and equally substantive efforts to protect the obtained effects. Expanding the elimination area, establishing effective post-elimination surveillance, and reducing underlying risk factors for transmission in cleared areas, are all critical steps to sustain elimination. Without these, in the eight years since the end of our program, we have seen transmission slowly regain footing in Tumbes, particularly in districts that experience frequent immigration from endemic areas outside the elimination zone (unpublished data, CWGP 2021), as unfortunate but sound evidence that interruption of T. solium transmission can be transient without active efforts to maintain this state.

Most national programs and international agencies shy away from advocating for elimination and prefer to refer to “control” goals. We strongly believe this is an unhealthy approach. “Control” is used to refer to any action, even if just declarative. Many countries claim to have active “control” programs, and yet no assessment of efficacy can be made since no monitoring data exist, and when available it is not easy to interpret. Variations in prevalence levels can occur for multiple reasons, (seasonality or differences in prevalence between districts, for example) and not necessarily mark a sustainable trend. Conversely, elimination of transmission as demonstrated by the absence of new viable infections in pigs, or no cases of taeniasis, is a hard indicator and it is either achieved or not.

Focal elimination of the transmission of Taenia solium and further expansion of elimination is not an easy task. Many aspects remain to be fine-tuned. Our program was designed to demonstrate that transmission could be interrupted, so interventions were maximized rather than optimized for a pragmatic and cost-effective approach. Expanding elimination efforts will require multiple fronts of action, from making diagnostic tools and drugs available, to designing regimes appropriate for each reality, to developing a practical and sustainable monitoring system and actions in case a residual or a new focus of transmission is detected. Access to diagnostic tools remains extremely limited and may require local capacity building before intervention. Although new interventions are tested sporadically in the research context, practices and mechanisms to implement these interventions as effective public health programs remain largely unaddressed. Monitoring and surveillance strategies remain to be defined. Differences in cultural and political acceptability will need to be explored so that interventions can be tailored to local realities. And efforts to improve conditions for sanitation, animal husbandry, and food safety, must be pursued in parallel, if not integrated with, therapeutic interventions.

Despite these challenges, we believe that achieving focal elimination and expanding these areas to widespread elimination and eventual eradication are the only sound pathway to eliminate NCC-associated epilepsy and other associated neurological disease, rather than waiting for decades for development to reach the poor, rural areas that are mostly burdened with this eradicable disease.