Efficacy and safety of antiparasitic therapy for neurocysticercosis in rural Tanzania: a prospective cohort study

D Stelzle, C Makasi, V Schmidt, C Trevisan, I Van Damme, C Ruether, P Dorny, P Magnussen, G Zulu, K E Mwape, E Bottieau, C Prazeres da Costa, U F Prodjinotho, H Carabin, E Jackson, A Fleury, S Gabriël, B J Ngowi, A S Winkler, D Stelzle, C Makasi, V Schmidt, C Trevisan, I Van Damme, C Ruether, P Dorny, P Magnussen, G Zulu, K E Mwape, E Bottieau, C Prazeres da Costa, U F Prodjinotho, H Carabin, E Jackson, A Fleury, S Gabriël, B J Ngowi, A S Winkler

Abstract

Purpose: Neurocysticercosis is common in regions endemic for Taenia solium. Active-stage neurocysticercosis can be treated with antiparasitic medication, but so far no study on efficacy and safety has been conducted in Africa.

Methods: We conducted a prospective cohort study on treatment of neurocysticercosis in Tanzania between August 2018 and January 2022. Patients were initially treated with albendazole (15 mg/kg/d) for 10 days and followed up for 6 months. Additionally in July 2021, all participants who then still had cysts were offered a combination therapy consisting of albendazole (15 mg/kg/d) and praziquantel (50 mg/kg/d). Antiparasitic treatment was accompanied by corticosteroid medication and anti-seizure medication if the patient had experienced epileptic seizures before treatment.

Results: Sixty-three patients were recruited for this study, of whom 17 had a complete follow-up after albendazole monotherapy. These patients had a total of 138 cysts at baseline, of which 58 (42%) had disappeared or calcified by the end of follow-up. The median cyst reduction was 40% (interquartile range 11-63%). Frequency of epileptic seizures reduced considerably (p < 0.001). Three patients had all active cysts resolved or calcified and of the remaining 14, eight received the combination therapy which resolved 63 of 66 cysts (95%). Adverse events were infrequent and mild to moderate during both treatment cycles.

Conclusion: Cyst resolution was unsatisfactory with albendazole monotherapy but was very high when it was followed by a combination of albendazole and praziquantel.

Keywords: Albendazole; Antiparasitic medication; Neglected tropical diseases; Neurocysticercosis; Praziquantel; Taenia solium.

Conflict of interest statement

The authors declare that there are no competing interests.

© 2023. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of the study. Eight patients with large number of lesions, one patient with lesion in the fourth ventricle
Fig. 2
Fig. 2
A Treatment efficacy in terms of cyst resolution by treatment regimen, and natural disease progression without antiparasitic treatmenta. aAlbendazole treatment (n = 8) refers to the eight patients who received first a treatment cycle with albendazole and because of incomplete cyst resolution afterwards treatment cycle with combination therapy. They are a subset of the 17 patients on the left. B Cyst resolution in the seventeen patients treated with albendazole monotherapy. C Cyst resolution in the eight patients treated with combination therapy
Fig. 3
Fig. 3
Change in quality of life from before and 6 months after combination therapy (A QOLIE-31, B WHOQOL-BREF)a. aMedian (point) and range of values (lines)

References

    1. Nyangi C, Stelzle D, Mkupasi EM, et al. Knowledge, attitudes and practices related to Taenia solium cysticercosis and taeniasis in Tanzania. BMC Infect Dis. 2022;22:534. doi: 10.1186/s12879-022-07408-0.
    1. Kabululu ML, Ngowi HA, Mlangwa JED, et al. Endemicity of Taenia solium cysticercosis in pigs from Mbeya Rural and Mbozi districts, Tanzania. BMC Vet Res. 2020;16:325. doi: 10.1186/s12917-020-02543-9.
    1. Stelzle D, Makasi C, Schmidt V, et al. Epidemiological, clinical and radiological characteristics of people with neurocysticercosis in Tanzania-A cross-sectional study. PLoS Negl Trop Dis. 2022;16:e0010911. doi: 10.1371/journal.pntd.0010911.
    1. Winkler AS. Neurocysticercosis in sub-Saharan Africa: a review of prevalence, clinical characteristics, diagnosis, and management. Pathog Glob Health. 2012;106:261–274. doi: 10.1179/2047773212y.0000000047.
    1. Ndimubanzi PC, Carabin H, Budke CM, et al. A systematic review of the frequency of neurocyticercosis with a focus on people with epilepsy. PLoS Negl Trop Dis. 2010;4:e870. doi: 10.1371/journal.pntd.0000870.
    1. Owolabi LF, Adamu B, Jibo AM, Owolabi SD, Imam AI, Alhaji ID. Neurocysticercosis in people with epilepsy in Sub-Saharan Africa: a systematic review and meta-analysis of the prevalence and strength of association. Seizure. 2020;76:1–11. doi: 10.1016/j.seizure.2020.01.005.
    1. Millogo A, Nitiéma P, Carabin H, et al. Prevalence of neurocysticercosis among people with epilepsy in rural areas of Burkina Faso. Epilepsia. 2012;53:2194–2202. doi: 10.1111/j.1528-1167.2012.03687.x.
    1. Stelzle D, Schmidt V, Keller L, et al. Characteristics of people with epilepsy and neurocysticercosis in three eastern African countries-A pooled analysis. PLoS Negl Trop Dis. 2022;16:e0010870. doi: 10.1371/journal.pntd.0010870.
    1. Keller L, Stelzle D, Schmidt V, et al. Community-level prevalence of epilepsy and of neurocysticercosis among people with epilepsy in the Balaka district of Malawi: a cross-sectional study. PLoS Negl Trop Dis. 2022;16:e0010675. doi: 10.1371/journal.pntd.0010675.
    1. Del Brutto OH, Robles AM, Mera RM, et al. Calcified neurocysticercosis and headache in an endemic village: a case-control study nested to a population-based cohort. Am J Trop Med Hyg. 2018;99:729–734. doi: 10.4269/ajtmh.18-0310.
    1. Carabin H, Ndimubanzi PC, Budke CM, et al. Clinical manifestations associated with neurocysticercosis: a systematic review. PLoS Negl Trop Dis. 2011;5:1152. doi: 10.1371/journal.pntd.0001152.
    1. Escobar A. The pathology of neurocysticercosis. In: Palacios E, Rodriguez-Carbajal KJ, Taveras J, editors. Cysticercosis of the central nervous system. Springfield: Charles C Thomas; 1983. pp. 27–54.
    1. Nash TE, Mahanty S, Loeb JA, et al. Neurocysticercosis: a natural human model of epileptogenesis. Epilepsia. 2015;56:177–183. doi: 10.1111/epi.12849.
    1. Nash TE, Pretell EJ, Lescano AG, et al. Perilesional brain oedema and seizure activity in patients with calcified neurocysticercosis: a prospective cohort and nested case-control study. Lancet Neurol. 2008;7:1099–1105. doi: 10.1016/S1474-4422(08)70243-6.
    1. Stelzle D, Abraham A, Kaminski M, et al. Clinical characteristics and management of neurocysticercosis patients: a retrospective assessment of case reports from Europe. J Travel Med. 2022 doi: 10.1093/jtm/taac102.
    1. World Health Organization . Guidelines on management of Taeniasolium neurocysticercosis. Geneva: WHO; 2021.
    1. White AC, Coyle CM, Rajshekhar V, et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH) Clin Infect Dis. 2018;66:e49–e75. doi: 10.1093/cid/cix1084.
    1. Garcia HH, Gonzales I, Lescano AG, et al. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis. 2014;14:687–695. doi: 10.1016/S1473-3099(14)70779-0.
    1. Garcia HH, Lescano AG, Gonzales I, et al. Cysticidal efficacy of combined treatment with praziquantel and albendazole for parenchymal brain cysticercosis. Clin Infect Dis. 2016;62:1375–1379. doi: 10.1093/cid/ciw134.
    1. Kaur S, Singhi P, Singhi S, Khandelwal N. Combination therapy with albendazole and praziquantel versus albendazole alone in children with seizures and single lesion neurocysticercosis: a randomized, placebo-controlled double blind trial. Pediatr Infect Dis J. 2009;28:403–406. doi: 10.1097/INF.0b013e31819073aa.
    1. Wang W. Combined antiparasitic treatment for neurocysticercosis. Lancet Infect Dis. 2015;15:265–266. doi: 10.1016/S1473-3099(15)70022-8.
    1. Mahamat A, Abboud P, Demar M, JeanBourquin D, Djossou F. Combined antiparasitic treatment for neurocysticercosis. Lancet Infect Dis. 2015;15:264–265. doi: 10.1016/S1473-3099(15)70031-9.
    1. Carpio A, Romo ML. Combined antiparasitic treatment for neurocysticercosis. Lancet Infect Dis. 2015;15:265. doi: 10.1016/S1473-3099(15)70025-3.
    1. Wu W, Jia F, Wang W, Huang Y, Huang Y. Antiparasitic treatment of cerebral cysticercosis: lessons and experiences from China. Parasitol Res. 2013;112:2879–2890. doi: 10.1007/s00436-013-3459-3.
    1. Guo D, Xie S, Jia J. Therapeutic efficacy of praziquantel, albendazole and a combination of the two drugs in cysticercosis. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2003;21:187–188.
    1. Cárdenas G, Carrillo-Mezo R, Jung H, Sciutto E, Hernandez JLS, Fleury A. Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series. BMC Neurol. 2010 doi: 10.1186/1471-2377-10-16.
    1. Monk EJM, Abba K, Ranganathan LN. Anthelmintics for people with neurocysticercosis. Cochrane Database Syst Rev. 2021;6:CD000215. doi: 10.1002/14651858.CD000215.pub5.
    1. Trevisan C, Damme I, Ngowi B, et al. Trial Design of a prospective multicenter diagnostic accuracy study of a point-of-care test for the detection of Taenia solium taeniasis and neurocysticercosis in Hospital-Based Settings in Tanzania. Diagnostics. 2021;11:1528. doi: 10.3390/diagnostics11091528.
    1. Del Brutto OH, Nash TE, White AC, et al. Revised diagnostic criteria for neurocysticercosis. J Neurol Sci. 2017;372:202–210. doi: 10.1016/j.jns.2016.11.045.
    1. Cramer JA, Perrine K, Devinsky O, Bryant-Comstock L, Meador K, Hermann B. Development and cross-cultural translations of a 31-item quality of life in epilepsy inventory. Epilepsia. 1998;39:81–88. doi: 10.1111/j.1528-1157.1998.tb01278.x.
    1. World Health Organization Quality of Life Group Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL. Group Psychol Med. 1998;28:551–558. doi: 10.1017/s0033291798006667.
    1. Todowede OO, Mianda SZ, Sartorius B. Prevalence of metabolic syndrome among HIV-positive and HIV-negative populations in sub-Saharan Africa-a systematic review and meta-analysis. Syst Rev. 2019;8:4. doi: 10.1186/s13643-018-0927-y.
    1. Prodjinotho UF, Lema J, Lacorcia M, et al. Host immune responses during Taenia solium neurocysticercosis infection and treatment. PLoS Negl Trop Dis. 2020;14:e0008005. doi: 10.1371/journal.pntd.0008005.
    1. Lacorcia M, Kugyelka R, Spechtenhauser L, et al. Praziquantel reduces maternal mortality and offspring morbidity by enhancing anti-helminthic immune responses. Front Immunol. 2022;13:878029. doi: 10.3389/fimmu.2022.878029.
    1. Martins-Leite P, Gazzinelli G, Alves-Oliveira LF, et al. Effect of chemotherapy with praziquantel on the production of cytokines and morbidity associated with schistosomiasis mansoni. Antimicrob Agents Chemother. 2008;52:2780–2786. doi: 10.1128/AAC.00173-08.
    1. Castro VN, Rodrigues JL, Cardoso DT, et al. Systemic cytokine and chemokine profiles in individuals with Schistosoma mansoni infection and low parasite burden. Front Immunol. 2018 doi: 10.3389/fimmu.2018.02975.
    1. Amha H, Memiah P, Getnet A, et al. Antiseizure medication nonadherence and its associated factors among Epileptic patients in Ethiopia, a systematic review and meta-analysis. Seizure. 2021;91:462–475. doi: 10.1016/j.seizure.2021.07.024.
    1. Dima SA, Shibeshi MS. Antiepileptic drug adherence in children in southern Ethiopia: a cross sectional study. PLoS ONE. 2022;17:e0263821. doi: 10.1371/journal.pone.0263821.
    1. Marshall C, Olaniyan T, Jalloh AA, et al. Survey of the perceived treatment gap in status epilepticus care across Sub-Saharan countries from the perspective of healthcare providers. Epilepsy Behav. 2021;125:108408. doi: 10.1016/j.yebeh.2021.108408.
    1. Garcia HH, Pretell EJ, Gilman RH, et al. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med. 2004;350:249–258. doi: 10.1056/NEJMoa031294.
    1. Rana A, Musto AE. The role of inflammation in the development of epilepsy. J Neuroinflamm. 2018 doi: 10.1186/s12974-018-1192-7.
    1. Alyu F, Dikmen M. Inflammatory aspects of epileptogenesis: contribution of molecular inflammatory mechanisms. Acta Neuropsychiatr. 2017;29:1–16. doi: 10.1017/neu.2016.47.
    1. Zapata WR, Yang SY, Bustos JA, et al. Quality of life in patients with symptomatic epilepsy due to neurocysticercosis. Epilepsy Behav. 2022;131:1668. doi: 10.1016/j.yebeh.2022.108668.

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