What is the aim of this review?
The aim of this review was to explore whether treatment with anthelmintics (drugs that kill worms) can benefit people with neurocysticercosis (an infection of the brain caused by the pork tapeworm). The primary outcome of the review was the impact of treatment on seizures (epilepsy). We collected and analysed all relevant studies (trials) to answer this question and found 16 studies. The most commonly reported outcomes were those relating to seizures and also the number and appearance of lesions caused by viable or degrading cysts (dormant worms) on brain imaging.
We found that the anthelmintic albendazole probably reduces the recurrence of seizures in people with neurocysticercosis with a single cyst (moderate-certainty evidence). We are uncertain whether albendazole reduces seizure recurrence for people with neurocysticercosis with more than one cyst (very low-certainty evidence). We found little information regarding another anthelmintic drug, praziquantel; therefore these results are applicable to albendazole only. Albendazole treatment also probably increases the clearance and evolution of cysts in people with neurocysticercosis (moderate-certainty evidence). Evolution of a cyst is progression to a later cyst stage, which is thought to be an improvement towards clearance.
What was studied in the review?
Neurocysticercosis is an infection of the brain with the pork tapeworm Taenia solium, which is caused by eating food or drinking water contaminated with the eggs of the worm. The eggs can travel from the gut to the brain, forming cysts in the brain that can cause various symptoms, the most common of which is seizures/epilepsy. Neurocysticercosis is found mainly in areas where people keep pigs and have poor sanitation facilities, and is a common cause of seizures in areas where it is prevalent.
People with neurocysticercosis may have single or multiple cysts, and their symptoms depend on the position and numbers of these cysts within the brain. Each cyst goes through the natural process of being alive and dormant (viable), degrading (non-viable), and then it resolves or calcifies. This process can take many years. The number, type, and position of the cysts can be seen on brain imaging (lesions).
Two anthelmintics (drugs to treat worm infections), albendazole and praziquantel, are often used to treat neurocysticercosis. However, it is uncertain whether they reduce or stop seizures and other symptoms, or make them worse. In theory, the body's immune response to cysts dying as a result of treatment could cause more swelling and damage to the brain.
What are the main results of the review?
We included 16 studies in the review. These studies compared treatment with an anthelmintic versus placebo (a mock tablet/pill resembling the anthelmintic) or no anthelmintic treatment in adults or children with neurocysticercosis diagnosed by brain imaging.
For people with a single cyst, treatment with albendazole probably reduces seizure recurrence (moderate-certainty evidence). Notably, all studies that contributed to this analysis only included people with non-viable cysts. For people with multiple cysts, the evidence was of very low certainty, therefore we are uncertain whether or not albendazole reduces seizure recurrence for this group of patients. The studies contributing to this finding included participants with cysts that were both viable and non-viable. We found very little information regarding praziquantel, therefore these results are apply to albendazole only.
Treatment with albendazole probably increases complete clearance of lesions on brain imaging as well as the evolution of cysts (from viable to non-viable to resolved or calcified) (moderate-certainty evidence). The studies contributing to this evidence included people with single and multiple cysts, both viable and non-viable.
More side effects were reported by participants treated with either albendazole or praziquantel compared to those receiving placebo or no anthelmintic. The most commonly reported side effects were headache, abdominal pain, and nausea/vomiting.
How up-to-date is this review?
We searched for studies that had been published up to 21 October 2020.
For participants with a single cyst, there was less seizure recurrence in the albendazole group compared to the placebo/no anthelmintic group. The studies contributing to this evidence only recruited participants with a non-viable intraparenchymal cyst. We are uncertain whether albendazole reduces seizure recurrence for participants with multiple cysts. We also found that albendazole probably increases radiological clearance and evolution of lesions. There were very few studies reporting praziquantel outcomes, and these findings apply to albendazole only.
Neurocysticercosis is a parasitic infection of the central nervous system by the larval stage of the pork tapeworm and is a common cause of seizures and epilepsy in endemic areas. Anthelmintics (albendazole or praziquantel) may be given alongside supportive treatment (antiepileptics/analgesia) with the aim of killing these larvae (cysticerci), with or without corticosteroid treatment. However, there are potential adverse effects of these drugs, and the cysticerci may eventually die without directed anthelminthic treatment.
To assess the effects of anthelmintics on people with neurocysticercosis.
We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, the WHO ICTRP, and ClinicalTrials.gov, up to 21 October 2020.
Randomized controlled trials comparing anthelmintics and supportive treatment (+/- corticosteroids) with supportive treatment alone (+/- corticosteroids) for people with neurocysticercosis.
Two review authors independently screened the title and abstract of all articles identified by the search. We obtained full-text articles to confirm the eligibility of all studies that passed screening. One review author extracted data, which a second review author checked. Two review authors assessed the risk of bias of each trial and performed GRADE assessments. In cases of disagreement at consensus discussion stage between review authors, we consulted a third review author. We calculated risk ratios (RR) for dichotomous variables, with 95% confidence intervals (CIs) for pooled data from studies with similar interventions and outcomes.
We included 16 studies in the review. Only two studies investigated praziquantel and did not report data in a format that could contribute to meta-analysis. Most results in this review are therefore applicable to albendazole versus placebo or no anthelmintic.
The aggregate analysis across all participants with neurocysticercosis did not demonstrate a difference between groups in seizure recurrence, but heterogeneity was marked (RR 0.94, 95% CI 0.78 to 1.14; 10 trials, 1054 participants; I2 = 67%; low-certainty evidence). When stratified by participants with a single cyst or multiple cysts, pooled analysis suggests that albendazole probably improves seizure recurrence for participants with a single cyst (RR 0.61, 95% CI 0.4 to 0.91; 5 trials, 396 participants; moderate-certainty evidence). All studies contributing to this analysis recruited participants with non-viable, intraparenchymal cysts only, and most participants were children. We are uncertain whether or not albendazole reduces seizure recurrence in participants with multiple cysts, as the certainty of the evidence is very low, although the direction of effect is towards albendazole causing harm (RR 2.05, 95% CI 1.28 to 3.31; 2 trials, 321 participants; very low-certainty evidence). This analysis included a large study containing a highly heterogeneous population that received an assessment of unclear risk for multiple 'Risk of bias' domains.
Regarding radiological outcomes, albendazole probably slightly improves the complete radiological clearance of lesions (RR 1.22, 95% CI 1.07 to 1.39; 13 trials, 1324 participants; moderate-certainty evidence) and the evolution of cysts (RR 1.27, 95% CI 1.10 to 1.47; 6 trials, 434 participants; moderate-certainty evidence).
More adverse events appeared to be observed in participants treated with either albendazole or praziquantel compared to those receiving placebo or no anthelmintic. The most commonly reported side effects were headache, abdominal pain, and nausea/vomiting.